PMID- 26894281 TI - Stereoselective Ag-Catalyzed 1,3-Dipolar Cycloaddition of Activated Trifluoromethyl-Substituted Azomethine Ylides. AB - A silver-catalyzed 1,3-dipolar cycloaddition of fluorinated azomethine ylides and activated olefins is reported. The reaction offers a straightforward and atom economical procedure for the preparation of fluorinated pyrrolidines. Broad scope and high levels of diastereoselectivity have been achieved simply by using AgOAc/PPh3 as the catalyst system. The high efficiency of the cycloaddition relies on the presence of a metal-coordinating group on the imine moiety, such as an ester or heteroaryl group. The asymmetric version of the cycloaddition has been developed by using Taniaphos as a chiral ligand. PMID- 26894282 TI - Noncoding RNAs, Emerging Regulators in Root Endosymbioses. AB - Endosymbiosis interactions allow plants to grow in nutrient-deficient soil environments. The arbuscular mycorrhizal (AM) symbiosis is an ancestral interaction between land plants and fungi, whereas nitrogen-fixing symbioses are highly specific for certain plants, notably major crop legumes. The signaling pathways triggered by specific lipochitooligosaccharide molecules involved in these interactions have common components that also overlap with plant root development. These pathways include receptor-like kinases, transcription factors (TFs), and various intermediate signaling effectors, including noncoding (nc)RNAs. These latter molecules have emerged as major regulators of gene expression and small ncRNAs, composed of micro (mi)RNAs and small interfering (si)RNAs, are known to control gene expression at transcriptional (chromatin) or posttranscriptional levels. In this review, we describe exciting recent data connecting variants of conserved si/miRNAs with the regulation of TFs, such as NSP2, NFY-A1, auxin-response factors, and AP2-like proteins, known to be involved in symbiosis. The link between hormonal regulations and these si- and miRNA-TF nodes is proposed in a model in which different feedback loops or regulations controlling endosymbiosis signaling are integrated. The diversity and emerging regulatory networks of young legume miRNAs are also highlighted. PMID- 26894283 TI - Genotypic, Phenotypic and Clinical Validation of GeneXpert in Extra-Pulmonary and Pulmonary Tuberculosis in India. AB - BACKGROUND: Newer molecular diagnostics have brought paradigm shift in early diagnosis of tuberculosis [TB]. WHO recommended use of GeneXpert MTB/RIF [Xpert] for Extra-pulmonary [EP] TB; critics have since questioned its efficiency. METHODS: The present study was designed to assess the performance of GeneXpert in 761 extra-pulmonary and 384 pulmonary specimens from patients clinically suspected of TB and compare with Phenotypic, Genotypic and Composite reference standards [CRS]. RESULTS: Comparison of GeneXpert results to CRS, demonstrated sensitivity of 100% and 90.68%, specificity of 100% and 99.62% for pulmonary and extra-pulmonary samples. On comparison with culture, sensitivity for Rifampicin [Rif] resistance detection was 87.5% and 81.82% respectively, while specificity was 100% for both pulmonary and extra-pulmonary TB. On comparison to sequencing of rpoB gene [Rif resistance determining region, RRDR], sensitivity was respectively 93.33% and 90% while specificity was 100% in both pulmonary and extra-pulmonary TB. GeneXpert assay missed 533CCG mutation in one sputum and dual mutation [517 & 519] in one pus sample, detected by sequencing. Sequencing picked dual mutation [529, 530] in a sputum sample sensitive to Rif, demonstrating, not all RRDR mutations lead to resistance. CONCLUSIONS: Current study reports observations in a patient care setting in a high burden region, from a large collection of pulmonary and extra-pulmonary samples and puts to rest questions regarding sensitivity, specificity, detection of infrequent mutations and mutations responsible for low-level Rif resistance by GeneXpert. Improvements in the assay could offer further improvement in sensitivity of detection in different patient samples; nevertheless it may be difficult to improve sensitivity of Rif resistance detection if only one gene is targeted. Assay specificity was high both for TB detection and Rif resistance detection. Despite a few misses, the assay offers major boost to early diagnosis of TB and MDR-TB, in difficult to diagnose pauci-bacillary TB. PMID- 26894284 TI - Biomaterials and host versus graft response: a short review. AB - Biomaterials and biotechnology are increasing becoming an important area in modern medicine. The main aim in this area is the development of materials, which are biocompatible to normal tissue. Tissue-implant interactions with molecular, biological and cellular characteristics at the implant-tissue interface are important for the use and development of implants. Implantation may cause an inflammatory and immune response in tissue, foreign body reaction, systemic toxicity and imminent infection. Tissue-implant interactions determine the implant life-period. The aims of the study are to consider the biological response to implants. Biomaterials and host reactions to implants and their mechanisms are also briefly discussed. PMID- 26894285 TI - The etiology of hypertransaminasemia in Turkish children. AB - The aim of this study was to investigate the causes of elevated levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in children. We analyzed the medical records for children aged 3 months to 18 years who presented to the hospital with ALT >45 IU/L and/or AST >50 IU/L, between 2012 and 2014, for various reasons, including those not related to liver disease. In total, 281 children met the study criteria. This group comprised of 125 (44.5%) females and 156 (55.5%) males. At the presentation, the most common patient complaint was fatigue (53.4%), while 15.7% of the patients reported no symptoms. The most common findings on the physical examination were jaundice and hepatomegaly. In 15% of the cases, the findings were normal. According to the diagnosis, the most common cause of the elevated transaminases were infections (34%), with hepatitis A virus (HAV) infection as the leading cause (18.9%). Drug-induced liver injury (DILI) was the cause in 18.1% of the cases and non-alcoholic fatty liver disease (NAFLD) in 11.1%. The highest transaminase levels were associated with HAV infection, while DILI and NAFLD caused only slightly elevated transaminases. Overall, our results show that the elevated transaminases in children are most often caused by infections, DILI, and NAFLD. In a majority of cases, elevated ALT and AST indicate liver disease, however, they could also be associated with conditions other than liver damage. Additionally, the elevated enzymes can be detected in completely healthy individuals. PMID- 26894286 TI - LGALS3 and AXIN1 gene variants playing role in the Wnt/ beta-catenin signaling pathway are associated with mucinous component and tumor size in colorectal cancer. AB - The Wnt pathway alterations have been identified in colorectal and many other cancer types. It has been reported that galectin-3 (which is encoded by the LGALS3 gene) alters the signaling mechanism in the Wnt/ beta-catenin pathway by binding to beta-catenin in colon and other cancers. AXIN1 is mainly responsible for the assembly of the beta-catenin destruction complex in the Wnt pathway. This study investigated the relationship of rs4644 and rs4652 variants of the LGALS3 gene and rs214250 variants of the AXIN1 gene to histopathological and clinical properties. Our study included a total of 236 patients, of whom 119 had colorectal cancer (42 women, 77 men) and 117 were healthy controls. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and allele specific oligonucleotide (ASO) PCR methods were used. In addition, the serum galectin-3 level was studied with the enzyme-linked immunosorbent assay (ELISA) method. For the rs4644 variant of the LGALS3 gene, the CC genotype a mucinous component was significantly more common than those without a mucinous component (p=0.026). C allele frequency of the rs214250 variant of the AXIN1 gene was significantly correlated to tumor size in the advanced tumor stage (p=0.022). The CCAACT haplotype was more common in colorectal cancer patients (p=0.022). Serum galectin-3 level was higher in the patient group compared to the control group (5.9+/- 0.69 ng/ml vs. 0.79+/-0.01 ng/ml; p<0.001). In conclusion, variants of LGALS3 and AXIN1 genes affect tumor sizes and the mucinous component via Wnt/ beta-catenin pathway in the pathogenesis of colorectal cancer. PMID- 26894287 TI - Cr(VI) reduction and immobilization by novel carbonaceous modified magnetic Fe3O4/halloysite nanohybrid. AB - In this work, a novel "Dumbbell-like" magnetic Fe3O4/Halloysite nanohybrid (Fe3O4/HNTs@C) with oxygen-containing organic group grafting on the surface of natural halloysite nanotubes (HNTs) and homogeneous Fe3O4 nanospheres selectively aggregating at the tips of modified halloysite nanotubes was successfully synthesized. XRD, TEM, IR spectroscopy, XPS and VSM were used to characterize this newly halloysite nanohybrid and its formation mechanism was discussed. Cr(VI) ions adsorption experiments showed that the Fe3O4/halloysite nanohybrid exhibited higher adsorption ability with a maximum adsorption capacity of 132 mg/L at 303K, which is about 100 times higher than that of unmodified halloysite nanotubes. More importantly, with the reduction of Fe3O4 and electron-donor effect of oxygen-containing organic groups, Cr(VI) ions were easily reduced into low toxicity Cr(III) and then adsorbed onto the surface of halloysite nanohybrid. In addition, appreciable magnetization was observed due to the aggregation of magnetite nanoparticles, which make adsorbent facility separated from aqueous solutions after Cr pollution adsorption. PMID- 26894288 TI - Investigating the formation and toxicity of nitrogen transformation products of diclofenac and sulfamethoxazole in wastewater treatment plants. AB - Diclofenac (DCF) and sulfamethoxazole (SMX) are highly consumed pharmaceuticals and concentrated in effluents from conventional wastewater treatment plants (WWTPs) since they are not completely eliminated. Under microbial mediated nitrification/denitrification processes occurring in nitrifying activated sludge DCF biotransformed into its nitroso and nitro derivatives (NO-DCF and NO2-DCF, respectively). SMX was biotransformed under denitrification conditions in water/sediment batch reactors into its nitro and desamino derivatives (NO2-SMX and Des-SMX, respectively). Four transformation products (TPs) from DCF and SMX were analized in wastewaters (WW) and receiving surface waters (SW). Nitrifying/denitrifying-derivatives of DCF and SMX were detected for the first time in WW and SW at one order of magnitude lower than their parent compounds. Relationships observed among levels of NO-DCF, NO2-DCF and nitrogen-species tentatively suggested that nitrification/denitrification processes are involved in nitration and nitrosation of DCF during biological WW treatment. Acute toxicity of analytes to Daphnia magna and Vibrio fischeri was assessed individually and in mixtures with other relevant micropollutants. Individual effects showed these compounds as not harmful and not toxic. However, synergism effects observed in mixtures evidenced that contribution of these compounds to overall toxicity of complex environmental samples, should not be dismissed. PMID- 26894289 TI - Automated cytochrome c oxidase bioassay developed for ionic liquids' toxicity assessment. AB - A fully automated cytochrome c oxidase assay resorting to sequential injection analysis (SIA) was developed for the first time and implemented to evaluate potential toxic compounds. The bioassay was validated by evaluation of 15 ionic liquids (ILs) with distinct cationic head groups, alkyl side chains and anions. The assay was based on cytochrome c oxidase activity reduction in presence of tested compounds and quantification of inhibitor concentration required to cause 50% of enzyme activity inhibition (EC50). The obtained results demonstrated that enzyme activity was considerably inhibited by BF4 anion and ILs incorporating non aromatic pyrrolidinium and tetrabutylphosphonium cation cores. Emim [Ac] and chol [Ac], on contrary, presented the higher EC50 values among the ILs tested. The developed automated SIA methodology is a simple and robust high-throughput screening bioassay and exhibited good repeatability in all the tested conditions (rsd<3.7%, n=10). Therefore, it is expected that due to its simplicity and low cost, the developed approach can be used as alternative to traditional screening assays for evaluation of ILs toxicity and identification of possible toxicophore structures. Additionally, the results presented in this study provide further information about ILs toxicity. PMID- 26894290 TI - MoS2/reduced graphene oxide hybrid with CdS nanoparticles as a visible light driven photocatalyst for the reduction of 4-nitrophenol. AB - Photocatalytic reduction of nitroaromatic compounds to aromatic amines using visible light is an attractive process that utilizes sunlight as the energy source for the chemical conversions. Herewith we synthesized a composite material consisting of CdS nanoparticles grown on the surface of MoS2/reduced graphene oxide (rGO) hybrid as a novel photocatalyst for the reduction of 4-nitrophenol (4 NP). The CdS-MoS2/rGO composite is shown as a high-performance visible light driven photocatalyst. Even without a noble-metal cocatalyst, the catalyst exhibited a great activity under visible light irradiation for the reduction of 4 NP to much less toxic 4-aminophenol (4-AP) with ammonium formate as the sacrificial agent. Composite CdS-0.03(MoS2/0.01rGO) was found to be the most effective photocatalyst for 4-NP reduction. The high photocatalytic performance is apparently resulted from the synergetic functions of MoS2 and graphene in the composite, i.e. the cocatalysts serve as both the active adsorption sites for 4 NP and electron collectors for the separation of electron-hole pairs generated by CdS nanoparticles. The laboratory results show that the CdS-MoS2/rGO composite is a low-cost and stable photocatalyst for effective reduction and detoxification of nitroaromatic compounds using solar energy. PMID- 26894291 TI - Low-energy hydraulic fracturing wastewater treatment via AC powered electrocoagulation with biochar. AB - Produced and flowback waters are the largest byproducts associated with unconventional oil and gas exploration and production. Sustainable and low cost technologies are needed to treat and reuse this wastewater to avoid the environmental problems associated with current management practices (i.e., deep well injection). This study presents a new process to integrate AC-powered electrocoagulation (EC) with granular biochar to dramatically reduce energy use and electrode passivation while achieving high treatment efficiency. Results show achieving a 99% turbidity and TSS removal for the AC-EC-biochar system only used 0.079 kWh/m(3) or 0.15 kWh/kg TSS, which is 70% lower than traditional DC-EC systems and orders of magnitude lower than previous studies. The amount of biochar added positively correlates with energy saving, and further studies are needed to improve organic carbon and salt removal through system integration. PMID- 26894292 TI - Appling hydrolysis acidification-anoxic-oxic process in the treatment of petrochemical wastewater: From bench scale reactor to full scale wastewater treatment plant. AB - A hydrolysis acidification (HA)-anoxic-oxic (A/O) process was adopted to treat a petrochemical wastewater. The operation optimization was carried out firstly by a bench scale experimental reactor. Then a full scale petrochemical wastewater treatment plant (PCWWTP, 6500 m(3) h(-1)) was operated with the same parameters. The results showed that the BOD5/COD of the wastewater increased from 0.30 to 0.43 by HA. The effluent COD was 54.4 mg L(-1) for bench scale reactor and 60.9 mg L(-1) for PCWWTP when the influent COD was about 480 mg L(-1) on optimized conditions. The organics measured by gas chromatography-mass spectrometry (GC-MS) reduced obviously and the total concentration of the 5 organics (1,3-dioxolane, 2 pentanone, ethylbenzene, 2-chloromethyl-1,3-dioxolane and indene) detected in the effluent was only 0.24 mg L(-1). There was no obvious toxicity of the effluent. However, low acute toxicity of the effluent could be detected by the luminescent bacteria assay, indicating the advanced treatment is needed. The clone library profiling analysis showed that the dominant bacteria in the system were Acidobacteria, Proteobacteria and Bacteriodetes. HA-A/O process is suitable for the petrochemical wastewater treatment. PMID- 26894293 TI - Evaluation of emerging contaminants in a drinking water treatment plant using electrodialysis reversal technology. AB - Emerging contaminants (EC) have gained much attention with globally increasing consumption and detection in aquatic ecosystems during the last two decades from ng/L to lower ug/L. The aim of this study was to evaluate the occurrence and removal of pharmaceutically active compounds (PhACs), endocrine disrupting chemicals (EDCs) and related compounds in a Drinking Water Treatment Plant (DWTP) treating raw water from the Mediterranean Llobregat River. The DWTP combined conventional treatment steps with the world's largest electrodialysis reversal (EDR) facility. 49 different PhACs, EDCs and related compounds were found above their limit of quantification in the influent of the DWTP, summing up to a total concentration of ECs between 1600-4200 ng/L. As expected, oxidation using chlorine dioxide and granular activated carbon filters were the most efficient technologies for EC removal. However, despite the low concentration detected in the influent of the EDR process, it was also possible to demonstrate that this process partially removed ionized compounds, thereby constituting an additional barrier against EC pollution in the product. In the product of the EDR system, only 18 out of 49 compounds were quantifiable in at least one of the four experimental campaigns, showing in all cases removals higher than 65% and often beyond 90% for the overall DWTP process. PMID- 26894294 TI - Extracellular production of tellurium nanoparticles by the photosynthetic bacterium Rhodobacter capsulatus. AB - The toxic oxyanion tellurite (TeO3(2-)) is acquired by cells of Rhodobacter capsulatus grown anaerobically in the light, via acetate permease ActP2 and then reduced to Te(0) in the cytoplasm as needle-like black precipitates. Interestingly, photosynthetic cultures of R. capsulatus can also generate Te(0) nanoprecipitates (TeNPs) outside the cells upon addition of the redox mediator lawsone (2-hydroxy-1,4-naphtoquinone). TeNPs generation kinetics were monitored to define the optimal conditions to produce TeNPs as a function of various carbon sources and lawsone concentration. We report that growing cultures over a 10 days period with daily additions of 1mM tellurite led to the accumulation in the growth medium of TeNPs with dimensions from 200 up to 600-700 nm in length as determined by atomic force microscopy (AFM). This result suggests that nucleation of TeNPs takes place over the entire cell growth period although the addition of new tellurium Te(0) to pre-formed TeNPs is the main strategy used by R. capsulatus to generate TeNPs outside the cells. Finally, X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FT-IR) analysis of TeNPs indicate they are coated with an organic material which keeps the particles in solution in aqueous solvents. PMID- 26894295 TI - Cross-linked poly(tetrahydrofuran) as promising sorbent for organic solvent/oil spill. AB - In this study, a series of different molecular weights of poly(tetrahydrofuran) (PTHF), which is one of the most important commercial polymers around the world, was condensed with tris[3-(trimethoxysilyl)propyl]isocyanurate (ICS) to generate a cross-linked 3-dimensional network in order to obtain organic solvent/oil sorbents having high swelling capacity. The prepared sorbents show high and fast swelling capacity in oils such as dichloromethane (DCM), tetrahydrofuran (THF), acetone, t-butyl methyl ether (MTBE), gasoline, euro diesel, and crude oil. The recovery of the absorbed oils from contaminated surfaces, especially from water, and the regeneration of the sorbents after several applications are effective. The characterization and thermal properties of the sorbents are identified by Fourier transform infrared spectroscopy (FTIR), solid-state (13)C and (29)Si cross-polarization magic angle spinning (CPMAS) nuclear magnetic resonance (NMR), differential scanning calorimetry (DSC) and thermal gravimetric analyses (TGA), respectively. The new usage area of PTHF is emerged by the preparation of PTHF based network structure with high oil absorption capacity and having excellent reusability as an oil absorbent for the removal of organic liquids from the spill site. PMID- 26894296 TI - Tumor-associated macrophages in gastric cancer: more than bystanders in tumor microenvironment. PMID- 26894297 TI - Assessment of Point-of-Care Diagnostics for G6PD Deficiency in Malaria Endemic Rural Eastern Indonesia. AB - BACKGROUND: Patients infected by Plasmodium vivax or Plasmodium ovale suffer repeated clinical attacks without primaquine therapy against latent stages in liver. Primaquine causes seriously threatening acute hemolytic anemia in patients having inherited glucose-6-phosphate dehydrogenase (G6PD) deficiency. Access to safe primaquine therapy hinges upon the ability to confirm G6PD normal status. CareStart G6PD, a qualitative G6PD rapid diagnostic test (G6PD RDT) intended for use at point-of-care in impoverished rural settings where most malaria patients live, was evaluated. METHODOLOGY/PRINCIPAL FINDINGS: This device and the standard qualitative fluorescent spot test (FST) were each compared against the quantitative spectrophotometric assay for G6PD activity as the diagnostic gold standard. The assessment occurred at meso-endemic Panenggo Ede in western Sumba Island in eastern Indonesia, where 610 residents provided venous blood. The G6PD RDT and FST qualitative assessments were performed in the field, whereas the quantitative assay was performed in a research laboratory at Jakarta. The median G6PD activity >= 5 U/gHb was 9.7 U/gHb and was considered 100% of normal activity. The prevalence of G6PD deficiency by quantitative assessment (<5 U/gHb) was 7.2%. Applying 30% of normal G6PD activity as the cut-off for qualitative testing, the sensitivity, specificity, positive predictive value, and negative predictive value for G6PD RDT versus FST among males were as follows: 100%, 98.7%, 89%, and 100% versus 91.7%, 92%, 55%, and 99%; P = 0.49, 0.001, 0.004, and 0.24, respectively. These values among females were: 83%, 92.7%, 17%, and 99.7% versus 100%, 92%, 18%, and 100%; P = 1.0, 0.89, 1.0 and 1.0, respectively. CONCLUSIONS/SIGNIFICANCE: The overall performance of G6PD RDT, especially 100% negative predictive value, demonstrates suitable safety for G6PD screening prior to administering hemolytic drugs like primaquine and many others. Relatively poor diagnostic performance among females due to mosaic G6PD phenotype is an inherent limitation of any current practical screening methodology. PMID- 26894298 TI - Risk of Second Non-Breast Primary Cancer in Male and Female Breast Cancer Patients: A Population-Based Cohort Study. AB - Female breast cancer patients have an increased risk of developing subsequent malignant diseases, but this issue is rarely discussed in regards to male breast cancer patients. Thus, we conducted a national survey that included 100,915 female and 578 male breast cancer patients to investigate the risk of second primary malignancy (SPM). During a follow-up period that included 529,782 person years, 3,153 cases of SPM developed. Compared with the general population, the standardized incidence ratio (SIR) of SPM in breast cancer patients was 1.51 [95% confidence interval (CI): 1.46-1.56]. The observed risk was significantly higher in male patients (SIR 2.17, 95% CI 1.70-2.73) and in patients whose age at breast cancer diagnosis was 40 years or younger (SIR 3.39, 95% CI 2.80-4.07), comparing to age-matched general population. Compared with the overall female population, the SIRs of female breast cancer patients with uterine (SIR: 2.66, 95% CI: 2.37 2.98), thyroid (SIR: 2.30, 95% CI: 2.02-2.62), and bone and soft tissue (SIR: 2.16, 95% CI: 1.56-2.91) cancers were significantly increased. Male breast cancer patients also displayed significantly higher SIRs for thyroid (SIR: 13.2, 95% CI: 1.60-47.69), skin (SIR: 8.24, 95% CI: 3.02-17.94) and head and neck (SIR: 4.41, 95% CI: 2.35-7.54) cancers. Among breast cancer patients, risk factors significantly associated with SPM included male gender, older age, chemotherapy treatment and comorbidity with liver cirrhosis. From our analysis, we concluded that the risk of SPM was significantly higher for both male and female breast cancer patients compared with the general population, suggesting that more intensive surveillance may be needed, especially in high-risk patients. PMID- 26894300 TI - Comparative Cytogenetics of the Congo African Grey Parrot (Psittacus erithacus). AB - The Congo African grey parrot (Psittacus erithacus, PER) is an endemic species of Central Africa, valued for its intelligence and listed as vulnerable due to poaching and habitat destruction. Improved knowledge about the P. erithacus genome is needed to address key biological questions and conservation of this species. The P. erithacus genome was studied using conventional and molecular cytogenetic approaches including Zoo-FISH. P. erithacus has a 'typical' parrot karyotype with 2n = 62-64 and 8 pairs of macrochromosomes. A distinct feature was a sharp macro-microchromosome boundary. Telomeric sequences were present at all chromosome ends and interstitially in PER2q, the latter coinciding with a C-band. NORs mapped to 4 pairs of microchromosomes which is in contrast to a single NOR in ancestral type avian karyotypes. Zoo-FISH with chicken macrochromosomes GGA1-9 and Z revealed patterns of conserved synteny similar to many other avian groups, though neighboring synteny combinations of GGA6/7, 8/9, and 1/4 were distinctive only to parrots. Overall, P. erithacus shared more Zoo-FISH patterns with neotropical macaws than Australian species such as cockatiel and budgerigar. The observations suggest that Psittaciformes karyotypes have undergone more extensive evolutionary rearrangements compared to the majority of other avian genomes. PMID- 26894299 TI - Mechanism of Action and Clinical Application of Tafamidis in Hereditary Transthyretin Amyloidosis. AB - Transthyretin (TTR) transports the retinol-binding protein-vitamin A complex and is a minor transporter of thyroxine in blood. Its tetrameric structure undergoes rate-limiting dissociation and monomer misfolding, enabling TTR to aggregate or to become amyloidogenic. Mutations in the TTR gene generally destabilize the tetramer and/or accelerate tetramer dissociation, promoting amyloidogenesis. TTR related amyloidoses are rare, fatal, protein-misfolding disorders, characterized by formation of soluble aggregates of variable structure and tissue deposition of amyloid. The TTR amyloidoses present with a spectrum of manifestations, encompassing progressive neuropathy and/or cardiomyopathy. Until recently, the only accepted treatment to halt progression of hereditary TTR amyloidosis was liver transplantation, which replaces the hepatic source of mutant TTR with the less amyloidogenic wild-type TTR. Tafamidis meglumine is a rationally designed, non-NSAID benzoxazole derivative that binds with high affinity and selectivity to TTR and kinetically stabilizes the tetramer, slowing monomer formation, misfolding, and amyloidogenesis. Tafamidis is the first pharmacotherapy approved to slow the progression of peripheral neurologic impairment in TTR familial amyloid polyneuropathy. Here we describe the mechanism of action of tafamidis and review the clinical data, demonstrating that tafamidis treatment slows neurologic deterioration and preserves nutritional status, as well as quality of life in patients with early-stage Val30Met amyloidosis. PMID- 26894301 TI - Mitochondrial dysfunction and lipid peroxidation in rat frontal cortex by chronic NMDA administration can be partially prevented by lithium treatment. AB - Chronic N-methyl-d-aspartate (NMDA) administration to rats may be a model to investigate excitotoxicity mediated by glutamatergic hyperactivity, and lithium has been reported to be neuroprotective. We hypothesized that glutamatergic hyperactivity in chronic NMDA injected rats would cause mitochondrial dysfunction and lipid peroxidation in the brain, and that chronic lithium treatment would ameliorate some of these NMDA-induced alterations. Rats treated with lithium for 6 weeks were injected i.p. 25 mg/kg NMDA on a daily basis for the last 21 days of lithium treatment. Brain was removed and frontal cortex was analyzed. Chronic NMDA decreased brain levels of mitochondrial complex I and III, and increased levels of the lipid oxidation products, 8-isoprostane and 4-hydroxynonenal, compared with non-NMDA injected rats. Lithium treatment prevented the NMDA induced increments in 8-isoprostane and 4-hydroxynonenal. Our findings suggest that increased chronic activation of NMDA receptors can induce alterations in electron transport chain complexes I and III and in lipid peroxidation in brain. The NMDA-induced changes may contribute to glutamate-mediated excitotoxicity, which plays a role in brain diseases such as bipolar disorder. Lithium treatment prevented changes in 8-isoprostane and 4-hydroxynonenal, which may contribute to lithium's reported neuroprotective effect and efficacy in bipolar disorder. PMID- 26894302 TI - Do T1a breast cancers profit from adjuvant systemic therapy? A multicenter retrospective cohort study of 325 T1a-patients. AB - Small tumor size (<=5 mm, T1a) carries an excellent prognosis. Controversy exists over the extent of the variety of treatment approaches. We therefore explored the effect of adjuvant systemic therapy (AST) on recurrence free survival (RFS) and overall survival (OAS) for the group of T1a-tumors. METHODS: The multicenter study population included 9625 early breast cancer patients, diagnosed between 1992 and 2008. 5196 patients were T1 (54.0 %) and 325 of these patients (3.4 %) were T1a. RESULTS: Compared to patients with AST RFS and OAS were significantly worse for patients who did not receive AST (RFS: p = 0.001; OAS: p = 0.021). Even N0-T1a-patients (n = 279) significantly profited from AST (RFS: p = 0.001; OAS: p = 0.006). Patients with at least one poor prognostic factor (HR-, HER2+, N1 or G3) without AST also showed a significantly worse outcome (RFS: p = 0.026; OAS: p = 0.024) compared to pT1a-patients with AST. Consensus guidelines state that the prognosis of patients with T1a that are N0 is uncertain even if HER2 is amplified or overexpressed. In our study nodal-negative (N0) T1a-patients (n = 279) without AST showed a significantly worse RFS (p = 0.001), and a significantly worse OAS (p = 0.006) compared to those patients with AST. In multivariate analysis even after adjusting by age, grading, hormonal receptor status, HER2/neu-status and nodal status T1a-patients without AST were associated with a significantly worse RFS resp. OAS compared to patient with AST (RFS: p = 0.002; OAS: p = 0.007). CONCLUSIONS: There is an association between AST and improved RFS or OAS for breast cancer patients with T1a tumors. PMID- 26894303 TI - The new WHO classification of ovarian, fallopian tube, and primary peritoneal cancer and its clinical implications. AB - INTRODUCTION: Molecular pathological research has contributed to improving the knowledge of different subtypes of ovarian cancer. In parallel with the implementation of the new FIGO staging classification, the WHO classification was revised. The latter is mainly based on the histopathological findings and defines the actual type of tumor. It has, therefore, also an important impact on prognosis and therapy of the patient. MATERIALS AND METHODS: The new WHO Classification of Ovarian Cancer published 2014 by Robert Kurman and co-authors is summarized. The major changes compared to the hitherto existing classification are presented. RESULTS: The new classification eliminates the previous focus of mesothelial origin of ovarian cancer. Instead, it features a discussion of tubal carcinogenesis of hereditary and some other high-grade serous carcinomas. The previously assumed pathogenesis pathway may be correct for some, but not for all, serous cancers. The new classification was established to classify ovarian cancer in a more consistent way. The earlier transitional cell type of ovarian cancer has been removed while seromucinous tumors have been added as a new entity. The role of some borderline tumors as one possible step in the progression from benign to invasive lesions is incorporated. The article summarizes the essential updates concerning serous, mucinous, seromucinous, endometrioid, clear-cell, and Brenner tumors. CONCLUSION: The new WHO classification takes into account the recent findings on the origin, pathogenesis, and prognosis of different ovarian cancer subtypes. The tubal origin of hereditary and some non-hereditary high grade serous cancers is mentioned in contrast to the hitherto theory of mesothelial origin of tumors. Seromucinous tumors represent a new entity. PMID- 26894304 TI - Adhesions and endometriosis: challenges in subfertility management : (An expert opinion of the ANGEL-The ANti-Adhesions in Gynaecology Expert PaneL-group). AB - There is molecular evidence that endometriosis has a negative impact on the ovaries, although the exact pathophysiology concerning endometriosis-associated subfertility is not known. The negative impact on the tubo-ovarian unit can be directly by distorting the anatomy, indirectly by invoking inflammation or by oxidative damage with poorer-quality oocytes. Endometriosis even seems to have a negative effect on pregnancy outcome after in vitro fertilization. PMID- 26894305 TI - Placenta previa and immediate outcome of the term offspring. AB - PURPOSE: Immediate neonatal outcome in pregnancies complicated by placenta previa is largely dependent on gestational age. We aimed to investigate whether placenta previa increases the risk for perinatal mortality and immediate morbidity of the offspring born at term. METHODS: A population-based cohort study included all singleton pregnancies, with and without placenta previa, delivered at term. Maternal and pregnancy characteristics as well as immediate neonatal morbidity and mortality were compared. Deliveries occurred between the years 1991-2013 in a tertiary medical center. Multiple pregnancies, and fetal congenital malformations were excluded. RESULTS: During the study period 233,123 consecutive term deliveries met the inclusion criteria; 0.2 % of the babies were born to mothers diagnosed with placenta previa. Women with placenta previa were significantly older and more likely to have had a previous cesarean section. Pregnancies were more likely to be complicated with pathological presentations and cesarean hysterectomies. Babies born at term following pregnancies with placenta previa were more likely to weigh less than 2500 g (OR 2.78 CI 1.9-3.9, p < 0.001). However, 5 min Apgar score and perinatal mortality rates were comparable between the groups. Neonatal outcomes remained comparable between the groups in a sub analysis of cesarean deliveries only. CONCLUSION: Although placenta previa pregnancies involve higher maternal morbidity rates, term offsprings are not at an increased risk for immediate adverse outcome. PMID- 26894306 TI - Difference in reproductive performance between two subtypes of bicornuate uterus. AB - PURPOSE: We compared reproductive outcome in patients with two subtypes of bicornuate uterus who underwent a Strassmann metroplasty procedure. METHODS: Eleven patients diagnosed using the R-AFS definition were divided into partial and complete type, then reproductive outcome following a Strassmann metroplasty was evaluated. RESULTS: All four patients with the partial type anomaly conceived and achieved a live birth, while none of the seven with the complete type anomaly were able to conceive. CONCLUSION: Patients with the partial type of bicornuate uterus showed a favorable prognosis after a Strassmann metroplasty. Conversely, those with the complete type should be treated as uterus didelphis, and not undergo a metroplasty. PMID- 26894307 TI - Correction: Unilateral Left-Hand Contractions Produce Widespread Depression of Cortical Activity after Their Execution. PMID- 26894308 TI - Rational Design, Synthesis, and Preliminary Structure-Activity Relationships of alpha-Substituted-2-Phenylcyclopropane Carboxylic Acids as Inhibitors of Salmonella typhimurium O-Acetylserine Sulfhydrylase. AB - Cysteine is a building block for several biomolecules that are crucial for living organisms. The last step of cysteine biosynthesis is catalyzed by O-acetylserine sulfydrylase (OASS), a highly conserved pyridoxal 5'-phosphate (PLP)-dependent enzyme, present in different isoforms in bacteria, plants, and nematodes, but absent in mammals. Beside the biosynthesis of cysteine, OASS exerts a series of "moonlighting" activities in bacteria, such as transcriptional regulation, contact-dependent growth inhibition, swarming motility, and induction of antibiotic resistance. Therefore, the discovery of molecules capable of inhibiting OASS would be a valuable tool to unravel how this protein affects the physiology of unicellular organisms. As a continuation of our efforts toward the synthesis of OASS inhibitors, in this work we have used a combination of computational and spectroscopic approaches to rationally design, synthesize, and test a series of substituted 2-phenylcyclopropane carboxylic acids that bind to the two S. typhymurium OASS isoforms at nanomolar concentrations. PMID- 26894309 TI - Improved detection of delirium, implementation and validation of the CAM-ICU in elderly Emergency Department patients. AB - OBJECTIVE: To evaluate the effect of routine use of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) on the diagnosis rate of delirium in elderly Emergency Department (ED) patients and the validity of the CAM-ICU in the ED setting. METHODS: This was a prospective observational study in a tertiary care academic ED. We compared the diagnosis rate of delirium before implementation of the CAM-ICU, without routine use of a screening tool, with the diagnosis rate after implementation of the CAM-ICU. All consecutive patients aged 70 years or older were enrolled. The diagnosis rate before implementation was based on chart review and after implementation on a positive CAM-ICU score. In a subsample, the presence of delirium was evaluated independently according to the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text revision (DSM-IV-TR) criteria to assess the validity of the CAM-ICU. RESULTS: The total study population included 968 patients: 490 before and 478 after implementation of the CAM-ICU. The two groups were not significantly different in patient characteristics. Before implementation of the CAM-ICU, delirium was diagnosed in 14 patients (3%) and after implementation in 48 patients (10%) (P<0.001). The sensitivity of the CAM-ICU for delirium in the ED setting was 100%, specificity was 98%, positive predictive value was 92%, and negative predictive value was 100%. CONCLUSION: The diagnosis rate of delirium after implementation of the CAM ICU was three-fold higher than before. The CAM-ICU is a reliable screening tool in the ED, with high sensitivity, specificity, and positive and negative predictive value. PMID- 26894310 TI - Understanding How People with Mental Health Difficulties Experience Substance Use. AB - BACKGROUND: Quantitative studies dominate research exploring reasons for substance use and experiences of substance use by people with mental health difficulties. This limits the depth of understanding which can be gained about these experiences. OBJECTIVES: In the present article, we synthesized current qualitative research in this area to provide enhanced theoretical knowledge of these experiences. METHODS: Following a systematic literature search, we identified 12 studies which explored how people with mental health difficulties experienced using substances, and which met additional inclusion criterion. We used Noblit and Hare's metaethnographic approach to qualitatively synthesize these studies. RESULTS: Synthesis led to the development of two themes; "substance use mediates acceptance and social inclusion" and "substance use provides perceived opportunities for control and power." CONCLUSIONS/IMPORTANCE: The findings suggest that in the studies reviewed people's motivation for substance use was embedded in social and psychological contexts. It indicated that substance use could provide perceived benefits such as mediating the impact of mental health stigma, enabling the development of alternative identities, increasing their sense of power and providing opportunities for social inclusion. Mental health and substance use workers should therefore aim to develop alternative opportunities for people with co-occurring disorders to gain such benefits, and seek to challenge mental health stigma. PMID- 26894311 TI - The Effects of Stigma on Recovery Attitudes in People With Anorexia Nervosa in Intensive Treatment. AB - Self-stigma in individuals with anorexia nervosa (AN) may affect engagement in intensive treatment. The objective of this study was to test a Model of Self Stigma to identify the influence of public stigma, internalized stigma, self esteem, and self-efficacy on recovery attitudes in individuals in inpatient treatment for AN. Using a cross-sectional design, 36 female participants with AN completed questionnaires during the first week of intensive inpatient treatment. Better attitude towards recovery was positively correlated with higher self esteem and self-efficacy and negatively correlated with greater internalized stigma and perceptions of others devaluing families of individuals with AN. Together, these factors accounted for 63% of the variance in recovery attitudes. Findings demonstrate the adverse effects perceived stigma towards families, self stigma, and self-esteem have on recovery attitudes in individuals with AN. Clinical interventions are needed to challenge internalized stigma and bolster self-esteem to enhance individuals' recovery efforts. PMID- 26894312 TI - Executive (Dys)Functioning and Impulsivity as Possible Vulnerability Factors for Aggression in Forensic Patients. AB - This study investigated whether executive dysfunction and impulsivity are both predictors of reactive aggression and is the first to use behavioral assessment of aggression in response to provocation by means of a personalized boxing body opponent bag giving harassing feedback. Aggressive behavior, self-reported aggression, executive functioning (ie, working memory, flexibility, and divided attention), and impulsivity dimensions (i.e., Sensation Seeking, Impulsive Decision Making, and [inadequate] Response Inhibition) were measured in 44 incarcerated psychiatric patients. Results show that both executive functioning (working memory) and impulsivity (Impulsive Decision Making) predicted self reported reactive aggression, whereas Response Inhibition was the only predictor for reactive aggressive behavioral responses. The study suggests that Response Inhibition is a stronger predictor of reactive aggressive behavior than executive capacities of working memory, flexibility, and divided attention. Therefore, future research should investigate whether (inadequate) Response Inhibition could also be a valuable predictor for violent recidivism. PMID- 26894313 TI - Improving Treatment Engagement for Returning Operation Enduring Freedom and Operation Iraqi Freedom Veterans With Posttraumatic Stress Disorder, Depression, and Suicidal Ideation. AB - Posttraumatic stress disorder (PTSD) is associated with increased risk of suicidal ideation among veterans of Operation Enduring Freedom and Operation Iraqi Freedom. This report examined the effectiveness of a brief phone-based cognitive-behavioral intervention on treatment seeking among suicidal and nonsuicidal Operation Enduring Freedom and Operation Iraqi Freedom veterans who screened positive for PTSD. Participants were randomized to the intervention or control conditions. We found that suicidal participants, regardless of condition, were twice as likely to attend treatment as nonsuicidal participants. Participants assigned to the control condition who did not indicate suicidality at baseline were less likely to attend treatment at both the 1- and 6-month follow-up interviews. Qualitative findings of the suicidal participants indicated PTSD and depressive symptoms, low social support, and infrequent positive coping mechanisms. Our finding indicates the effectiveness of an intervention to motivate veterans with PTSD to initiate and remain in treatment. The intervention might be particularly useful prior to experiencing a psychological crisis. PMID- 26894314 TI - Reliability and Validity of Prototype Diagnosis for Adolescent Psychopathology. AB - The current study investigated the interrater reliability and validity of prototype ratings of 5 common adolescent psychiatric disorders: attention deficit/hyperactivity disorder, conduct disorder, major depressive disorder, generalized anxiety disorder, and posttraumatic stress disorder. One hundred fifty-seven adolescent inpatient participants consented to participate in this study. We compared ratings from 2 inpatient clinicians, blinded to each other's ratings and patient measures, after their separate initial diagnostic interview to assess interrater reliability. Prototype ratings completed by clinicians after their initial diagnostic interview with adolescent inpatients and outpatients were compared with patient-reported behavior problems and parents' report of their child's behavioral problems. Prototype ratings demonstrated good interrater reliability. Clinicians' prototype ratings showed predicted relationships with patient-reported behavior problems and parent-reported behavior problems. Prototype matching seems to be a possible alternative for psychiatric diagnosis. Prototype ratings showed good interrater reliability based on clinicians unique experiences with the patient (as opposed to video-/audio-recorded material) with no training. PMID- 26894315 TI - Defense Mechanisms in Adolescence as Predictors of Adult Personality Disorders. AB - Our study examines whether defense styles and separate defenses in depressed adolescent outpatients predict adult personality disorders (PDs). We obtained data from consecutive adolescent outpatients who participated in the Adolescent Depression Study at baseline and at the 8-year follow-up (N = 140). Defense styles were divided into mature, neurotic, image-distorting, and immature and a secondary set of analyses were made with separate defenses as predictors of a PD diagnosis. Neurotic, image-distorting, and immature defense styles in adolescence were associated with adulthood PDs. Neurotic defense style associated with cluster B diagnosis and image-distorting defense style associated with cluster A diagnosis. Separate defenses of displacement, isolation, and reaction formation were independent predictors of adult PD diagnosis even after adjusting for PD diagnosis in adolescence. Defense styles and separate defenses predict later PDs and could be used in the focusing of treatment interventions for adolescents. PMID- 26894316 TI - Engaging African-American Veterans in Mental Health Care: Patients' Perspectives. AB - Despite growing interest in patient engagement, the concept remains poorly defined. Moreover, patients' perspectives on engagement are lacking, particularly those of minority patients. A better understanding of patients' views and what influences their engagement in health services will facilitate better patient education and implementation practices to enhance patient participation in health care. This article addresses patients' perspectives of facilitators and barriers to engagement in outpatient mental health services. Forty-nine African-American veterans with mental illness receiving routine medication management visits were interviewed. Qualitative data analysis was guided by a constructivist grounded theory approach. Participants identified several barriers and facilitators to engagement in mental health services, including patient as well as provider related factors. Results emphasize the role of providers in facilitating sustained involvement of patients in their own care. Based on the findings, the authors offer a preliminary framework for patient engagement that encompasses patient and provider factors. PMID- 26894317 TI - Anxiety Sensitivity Among First-Time Fathers Moderates the Relationship Between Exposure to Stress During Birth and Posttraumatic Stress Symptoms. AB - This longitudinal study examined posttraumatic stress disorder (PTSD) and anxiety symptoms among men attending the birth of their first offspring. Furthermore, we examined the moderating role of anxiety sensitivity (AS) and intolerance of uncertainty in the association between exposure to stress during birth and PTSD and anxiety symptoms. Participants were Israeli men (n = 171) who were assessed with self-report questionnaires during the third trimester of pregnancy (T1) and approximately a month following birth (T2). Results show that the rates of postnatal PTSD and anxiety symptoms were relatively low. Subjective exposure to stress during birth and AS predicted PTSD in T2, above and beyond other negative life events and PTSD in T1. In addition, AS moderated the relations between subjective exposure to stress during birth and PTSD symptoms. Pregnancy and childbirth professionals may benefit from the insight that men with high levels of AS might experience childbirth as a highly stressful situation with possible posttraumatic stress symptoms. PMID- 26894318 TI - Pharmacotherapies for Posttraumatic Stress Disorder: A Meta-Analysis. AB - The purpose of this study was to assess the acceptability and efficacy of all types of pharmacotherapeutic agents in reducing the symptoms of posttraumatic stress disorder (PTSD). In this systematic meta-analysis, the dropout and response rates of various pharmacotherapy and placebo treatments reported by randomized clinical trials were compared. A total of 34 reports that described the acceptability and efficacy of PTSD pharmacotherapies were retrieved and analyzed. Of them, 30 trials examined the dropout rate as an index of acceptability and revealed the superiority of the PTSD pharmacotherapy to placebos (odds ratio, 0.75; 95% confidence interval, 0.66-0.86; n = 4313). The response rate was determined in 20 trials as an index of efficacy, showing that the PTSD pharmacotherapies were superior to the placebos (odds ratio, 1.47; 95% confidence interval, 1.34-1.62; n = 2166). Pharmacotherapy is an important component of the care of patients with PTSD. PMID- 26894319 TI - Emotional Freedom Techniques for Anxiety: A Systematic Review With Meta-analysis. AB - Emotional Freedom Technique (EFT) combines elements of exposure and cognitive therapies with acupressure for the treatment of psychological distress. Randomized controlled trials retrieved by literature search were assessed for quality using the criteria developed by the American Psychological Association's Division 12 Task Force on Empirically Validated Treatments. As of December 2015, 14 studies (n = 658) met inclusion criteria. Results were analyzed using an inverse variance weighted meta-analysis. The pre-post effect size for the EFT treatment group was 1.23 (95% confidence interval, 0.82-1.64; p < 0.001), whereas the effect size for combined controls was 0.41 (95% confidence interval, 0.17 0.67; p = 0.001). Emotional freedom technique treatment demonstrated a significant decrease in anxiety scores, even when accounting for the effect size of control treatment. However, there were too few data available comparing EFT to standard-of-care treatments such as cognitive behavioral therapy, and further research is needed to establish the relative efficacy of EFT to established protocols. PMID- 26894320 TI - Religion as a Risk Factor for Suicide Attempt and Suicide Ideation Among Depressed Patients. AB - We aimed to examine the relationship between religion and suicide attempt and ideation. Three hundred twenty-one depressed patients were recruited from mood disorder research studies at the New York State Psychiatric Institute. Participants were interviewed using the Structured Clinical Interview for DSM Disorders, Columbia University Suicide History form, Scale for Suicide Ideation, and Reasons for Living Inventory. Participants were asked about their religious affiliation, importance of religion, and religious service attendance. We found that past suicide attempts were more common among depressed patients with a religious affiliation (odds ratio, 2.25; p = 0.007). Suicide ideation was greater among depressed patients who considered religion more important (coefficient, 1.18; p = 0.026) and those who attended services more frequently (coefficient, 1.99; p = 0.001). We conclude that the relationship between religion and suicide risk factors is complex and can vary among different patient populations. Physicians should seek deeper understanding of the role of religion in an individual patient's life in order to understand the person's suicide risk factors more fully. PMID- 26894322 TI - Lower urinary tract symptoms and urodynamic findings in children and adults with cerebral palsy: A systematic review. AB - AIMS: To systematically review the scientific literature addressing lower urinary tract symptoms (LUTS) and urodynamic findings in adults and children with Cerebral Palsy (CP). Prognostic factors were also investigated. METHODS: A systematic research was conducted on the electronic databases PubMed, Web of Science, and CINAHL. Only full text clinical trials which examined the prevalence of LUTS or urodynamic findings in children or adults with CP were eligible. LUTS and urodynamic findings, defined by the International Children's Continence Society, were extracted from the included studies. Pooled average of extracted data was calculated. Studies were scored on methodological and reporting quality using the Dutch Cochrane Checklist, EBRO guidelines, and the Strengthening the Reporting of Observational Studies in Epidemiology Statement (STROBE) checklist. RESULTS: Twenty-seven studies fulfilled selection criteria. Methodological and reporting quality were moderate to low. An average of 55.5% of subjects with CP experience one or more LUTS. Storage symptoms are more common than voiding symptoms due to the high prevalence of neurogenic detrusor overactivity. Patients with voiding symptoms and pelvic floor overactivity are more prone to progress to upper urinary tract dysfunction in adult life. Urodynamic evaluation can direct management. Negative prognostic factors are the spastic subtype with quadriplegic distribution, moderate to severe functional impairment (GMFCS III or higher) and severe cognitive impairment. CONCLUSION: The significant prevalence of LUTS, risk for deterioration, and the impact of urinary tract symptoms on quality of life and health status warrants the need for evaluation and treatment in further research. Neurourol. Urodynam. 36:541-549, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 26894323 TI - Measurement of (23)Na(n,2n) cross section in well-defined reactor spectra. AB - The present paper aims to compare the calculated and experimental reaction rates of (23)Na(n,2n)(22)Na in a well-defined reactor spectra of a special core assembled in the LR-0 reactor. The experimentally determined reaction rate, derived using gamma spectroscopy of irradiated NaF sample, is used for average cross section determination. The resulting value averaged in spectra is 0.91+/ 0.02ub. This cross-section is important as it is included in International Reactor Dosimetry and Fusion File and is also relevant to the correct estimation of long-term activity of Na coolant in Sodium Fast Reactors. The calculations were performed with the MCNP6 code using ENDF/B-VII.0, JEFF-3.1, JEFF-3.2, JENDL 3.3, JENDL-4, ROSFOND-2010 and CENDL-3.1 nuclear data libraries. Generally the best C/E agreement, within 2%, was found using the ROSFOND-2010 data set, whereas the worst, as high as 40%, was found using the ENDF/B-VII.0. PMID- 26894321 TI - New use for an old drug: COX-independent anti-inflammatory effects of sulindac in models of cystic fibrosis. AB - BACKGROUND AND PURPOSE: Pulmonary disease is the main cause of morbidity and mortality in cystic fibrosis (CF) patients due to exacerbated inflammation. To date, the only anti-inflammatory drug available to CF patients is high-dose ibuprofen, which can slow pulmonary disease progression, but whose cyclooxygenase dependent digestive adverse effects limit its clinical use. Here we have tested sulindac, another non-steroidal anti-inflammatory drug with an undefined anti inflammatory effect in CF airway epithelial cells. EXPERIMENTAL APPROACH: Using in vitro and in vivo models, we NF-kappaB activity and IL-8 secretion. In HeLa F508del cells, we performed luciferase reporter gene assays in order to measure i) IL-8 promoter activity, and ii) the activity of synthetic promoter containing NF-kappaB responsive elements. We quantified IL-8 secretion in airway epithelial CFBE cells cultured at an air-liquid interface and in a mouse model of CF. KEY RESULTS: Sulindac inhibited the transcriptional activity of NF-kappaB and decreased IL-8 transcription and secretion in TNF-alpha stimulated CF cells via a cyclooxygenase-independent mechanism. This effect was confirmed in vivo in a mouse model of CF induced by intra-tracheal instillation of LPS, with a significant decrease of the induction of mRNA for MIP-2, following treatment with sulindac. CONCLUSION AND IMPLICATIONS: Overall, sulindac decrease lung inflammation by a mechanism independent of cycolooxygenase. This drug could be beneficially employed in CF. PMID- 26894324 TI - The Association Between Childhood Seizures and Later Childhood Emotional and Behavioral Problems: Findings From a Nationally Representative Birth Cohort. AB - OBJECTIVES: Emotional/behavioral disorders are often comorbid with childhood epilepsy, but both may be predicted by social disadvantage and fetal risk indicators (FRIs). We used data from a British birth cohort, to assess the association of epilepsy, single unprovoked seizures, and febrile seizures with the later development of emotional/behavioral problems. METHODS: A total of 17,416 children in the 1958 British birth cohort were followed up until age 16 years. Logistic and modified Poisson regression models were used to determine a) the association of social disadvantage at birth and FRI with epilepsy, single unprovoked seizures, and febrile seizures at 7 years, and emotional/behavioral disorders in later childhood, and (ii) the association of childhood seizures by age 7 years with emotional/behavioral disorders in later childhood, after accounting for social disadvantage and FRI. RESULTS: Higher scores on FRI and social disadvantage were associated with emotional/behavioral problems at 7, 11, and 16 years, but not with seizure disorders at age 7 years. Epilepsy was associated with emotional/behavioral problems at 7 years (odds ratio [OR] = 2.50, 95% confidence interval [CI] = 1.29-4.84), 11 years (OR = 2.00, 95% CI = 1.04 3.81), and 16 years (OR = 5.47, 95% CI = 1.65-18.08), whereas single unprovoked seizures were associated with emotional/behavioral problems at 16 years (OR = 1.44, 95% CI = 1.02-2.01), after adjustment for FRI and social disadvantage. Febrile convulsions were not associated with increased risk for emotional/behavioral problems. CONCLUSIONS: Emotional/behavioral problems in children are related to an earlier diagnosis of epilepsy and single unprovoked seizures after accounting for social disadvantage and FRI, whereas febrile convulsions are not associated with emotional/behavioral problems. PMID- 26894326 TI - Mortality After Bereavement: The Role of Cardiovascular Disease and Depression. AB - OBJECTIVES: Late-life bereavement is associated with an increased risk of mortality. This study assesses the associations among bereavement, cardiovascular disease (CVD), and depressive symptoms on mortality in older men and women. METHODS: We examined data from the Cardiovascular Health Study, a prospective population-based cohort study of older adults. We compared mortality in those who became bereaved from 1989 to 1999 (n = 593) to an age- and sex-matched sample of individuals who remained married (n = 593). Cox regression was used to examine the association between bereavement and 3-year all-cause mortality and whether or not the association differed by sex, presence of CVD, or postbereavement depressive symptoms. RESULTS: One hundred ninety-nine (16.8%) individuals died. There was no association of bereavement with mortality (hazard ratio [HR] = 0.98 [0.74-1.30]). However, there were significant interaction effects of bereavement with participant sex (p < .001) and CVD (p = .010). Bereavement decreased the risk of mortality in women (HR = 0.67 [0.46-0.97]) and increased the risk of mortality in men (HR = 1.77 [1.14-2.75]). Within sex, the association of bereavement with mortality differed according to CVD status. The reduced risk of mortality associated with bereavement in women was only observed in women with CVD, and the increased risk in men was only observed in men without CVD. High levels of depressive symptoms attenuated the relation between bereavement and mortality in men without CVD. CONCLUSIONS: The relation between bereavement and mortality was different in men and women and varied by CVD status. Bereavement decreased mortality in women with CVD and increased mortality in men without CVD. PMID- 26894327 TI - Unbiased Prediction and Feature Selection in High-Dimensional Survival Regression. AB - With widespread availability of omics profiling techniques, the analysis and interpretation of high-dimensional omics data, for example, for biomarkers, is becoming an increasingly important part of clinical medicine because such datasets constitute a promising resource for predicting survival outcomes. However, early experience has shown that biomarkers often generalize poorly. Thus, it is crucial that models are not overfitted and give accurate results with new data. In addition, reliable detection of multivariate biomarkers with high predictive power (feature selection) is of particular interest in clinical settings. We present an approach that addresses both aspects in high-dimensional survival models. Within a nested cross-validation (CV), we fit a survival model, evaluate a dataset in an unbiased fashion, and select features with the best predictive power by applying a weighted combination of CV runs. We evaluate our approach using simulated toy data, as well as three breast cancer datasets, to predict the survival of breast cancer patients after treatment. In all datasets, we achieve more reliable estimation of predictive power for unseen cases and better predictive performance compared to the standard CoxLasso model. Taken together, we present a comprehensive and flexible framework for survival models, including performance estimation, final feature selection, and final model construction. The proposed algorithm is implemented in an open source R package (SurvRank) available on CRAN. PMID- 26894325 TI - Actigraphy- and Polysomnography-Measured Sleep Disturbances, Inflammation, and Mortality Among Older Men. AB - OBJECTIVES: To evaluate whether objectively measured sleep characteristics are associated with mortality risk independent of inflammatory burden and comorbidity. METHODS: The Osteoporotic Fractures in Men Sleep Study (conducted in 2003-2005) included community-dwelling older men (n = 2531; average [standard deviation {SD}] age = 76.3 (5.5) years). Sleep measures from in-home polysomnography and wrist actigraphy and assessments of serum inflammatory markers levels (C-reactive protein, interleukin-6, tumor necrosis factor alpha, tumor necrosis factor alpha soluble receptor II, and interferon-gamma) were obtained. Vital status was ascertained over an average (SD) follow-up of 7.4 (1.9 SD) years. RESULTS: Three of the seven main sleep measures examined were independently associated with greater inflammatory burden. Mortality risk associated with prolonged (>=10% total sleep time) blood oxygen desaturation and short (<5 hours) sleep duration was attenuated to nonsignificance after adjusting for inflammatory burden or medical burden/lifestyle factors. Severe blood oxygen desaturation (adjusted hazard ratio [aHR] = 1.57, 95% confidence interval [CI] = 1.11-2.22), sleep fragmentation (aHR = 1.32, 95% CI = 1.12-1.57), and a lower percentage of sleep in rapid eye movement (aHR per SD = 0.90, 95% CI = 0.93-0.97) were independently associated with mortality. CONCLUSIONS: Short sleep duration and prolonged blood oxygen desaturation were independently associated with inflammatory burden, which attenuated associations between these sleep characteristics and mortality. Medical and life-style factors also substantially attenuated most sleep-mortality associations, suggesting complex relations between sleep, inflammation, and disease. Sleep fragmentation, severe blood oxygen desaturation, and the percentage of sleep time in rapid eye movement were independently related to mortality risk. Future studies with repeated measures of mediators/confounds will be necessary to achieve a mechanistic understanding of sleep-related mortality risk. PMID- 26894328 TI - Metagenomic analysis of viruses associated with field-grown and retail lettuce identifies human and animal viruses. AB - The emergence of culture- and sequence-independent metagenomic methods has not only provided great insight into the microbial community structure in a wide range of clinical and environmental samples but has also proven to be powerful tools for pathogen detection. Recent studies of the food microbiome have revealed the vast genetic diversity of bacteria associated with fresh produce. However, no work has been done to apply metagenomic methods to tackle viruses associated with fresh produce for addressing food safety. Thus, there is a little knowledge about the presence and diversity of viruses associated with fresh produce from farm-to fork. To address this knowledge gap, we assessed viruses on commercial romaine and iceberg lettuces in fields and a produce distribution center using a shotgun metagenomic sequencing targeting both RNA and DNA viruses. Commercial lettuce harbors an immense assemblage of viruses that infect a wide range of hosts. As expected, plant pathogenic viruses dominated these communities. Sequences of rotaviruses and picobirnaviruses were also identified in both field-harvest and retail lettuce samples, suggesting an emerging foodborne transmission threat that has yet to be fully recognized. The identification of human and animal viruses in lettuce samples in the field emphasizes the importance of preventing viral contamination on leafy greens starting at the field. Although there are still some inherent experimental and bioinformatics challenges in applying viral metagenomic approaches for food safety testing, this work will facilitate further application of this unprecedented deep sequencing method to food samples. PMID- 26894329 TI - A neural network-based 2D/3D image registration quality evaluator for pediatric patient setup in external beam radiotherapy. AB - Our purpose was to develop a neural network-based registration quality evaluator (RQE) that can improve the 2D/3D image registration robustness for pediatric patient setup in external beam radiotherapy. Orthogonal daily setup X-ray images of six pediatric patients with brain tumors receiving proton therapy treatments were retrospectively registered with their treatment planning computed tomography (CT) images. A neural network-based pattern classifier was used to determine whether a registration solution was successful based on geometric features of the similarity measure values near the point-of-solution. Supervised training and test datasets were generated by rigidly registering a pair of orthogonal daily setup X-ray images to the treatment planning CT. The best solution for each registration task was selected from 50 optimizing attempts that differed only by the randomly generated initial transformation parameters. The distance from each individual solution to the best solution in the normalized parametrical space was compared to a user-defined error tolerance to determine whether that solution was acceptable. A supervised training was then used to train the RQE. Performance of the RQE was evaluated using test dataset consisting of registration results that were not used in training. The RQE was integrated with our in-house 2D/3D registration system and its performance was evaluated using the same patient dataset. With an optimized sampling step size (i.e., 5 mm) in the feature space, the RQE has the sensitivity and the specificity in the ranges of 0.865-0.964 and 0.797-0.990, respectively, when used to detect registration error with mean voxel displacement (MVD) greater than 1 mm. The trial-to-acceptance ratio of the integrated 2D/3D registration system, for all patients, is equal to 1.48. The final acceptance ratio is 92.4%. The proposed RQE can potentially be used in a 2D/3D rigid image registration system to improve the overall robustness by rejecting unsuccessful registration solutions. The RQE is not patient-specific, so a single RQE can be constructed and used for a particular application (e.g., the registration for images acquired on the same anatomical site). Implementation of the RQE in a 2D/3D registration system is clinically feasible. PMID- 26894330 TI - On the sensitivity of TG-119 and IROC credentialing to TPS commissioning errors. AB - We investigate the sensitivity of IMRT commissioning using the TG-119 C-shape phantom and credentialing with the IROC head and neck phantom to treatment planning system commissioning errors. We introduced errors into the various aspects of the commissioning process for a 6X photon energy modeled using the analytical anisotropic algorithm within a commercial treatment planning system. Errors were implemented into the various components of the dose calculation algorithm including primary photons, secondary photons, electron contamination, and MLC parameters. For each error we evaluated the probability that it could be committed unknowingly during the dose algorithm commissioning stage, and the probability of it being identified during the verification stage. The clinical impact of each commissioning error was evaluated using representative IMRT plans including low and intermediate risk prostate, head and neck, mesothelioma, and scalp; the sensitivity of the TG-119 and IROC phantoms was evaluated by comparing dosimetric changes to the dose planes where film measurements occur and change in point doses where dosimeter measurements occur. No commissioning errors were found to have both a low probability of detection and high clinical severity. When errors do occur, the IROC credentialing and TG 119 commissioning criteria are generally effective at detecting them; however, for the IROC phantom, OAR point-dose measurements are the most sensitive despite being currently excluded from IROC analysis. Point-dose measurements with an absolute dose constraint were the most effective at detecting errors, while film analysis using a gamma comparison and the IROC film distance to agreement criteria were less effective at detecting the specific commissioning errors implemented here. PMID- 26894331 TI - A new method and device of aligning patient setup lasers in radiation therapy. AB - The aim of this study is to develop a new method to align the patient setup lasers in a radiation therapy treatment room and examine its validity and efficiency. The new laser alignment method is realized by a device composed of both a metallic base plate and a few acrylic transparent plates. Except one, every plate has either a crosshair line (CHL) or a single vertical line that is used for alignment. Two holders for radiochromic film insertion are prepared in the device to find a radiation isocenter. The right laser positions can be found optically by matching the shadows of all the CHLs in the gantry head and the device. The reproducibility, accuracy, and efficiency of laser alignment and the dependency on the position error of the light source were evaluated by comparing the means and the standard deviations of the measured laser positions. After the optical alignment of the lasers, the radiation isocenter was found by the gantry and collimator star shots, and then the lasers were translated parallel to the isocenter. In the laser position reproducibility test, the mean and standard deviation on the wall of treatment room were 32.3 +/- 0.93 mm for the new method whereas they were 33.4 +/- 1.49 mm for the conventional method. The mean alignment accuracy was 1.4 mm for the new method, and 2.1 mm for the conventional method on the walls. In the test of the dependency on the light source position error, the mean laser position was shifted just by a similar amount of the shift of the light source in the new method, but it was greatly magnified in the conventional method. In this study, a new laser alignment method was devised and evaluated successfully. The new method provided more accurate, more reproducible, and faster alignment of the lasers than the conventional method. PMID- 26894332 TI - Confidence limits for patient-specific IMRT dose QA: a multi-institutional study in Korea. AB - This study aims to investigate tolerance levels for patient-specific IMRT dose QA (DQA) using the confidence limits (CL) determined by a multi-institutional study. Eleven institutions participated in the multi-institutional study in Korea. A total of 155 DQA measurements, consisting of point-dose differences (high- and low-dose regions) and gamma passing rates (composite and per-field) for IMRT patients with brain, head and neck (H&N), abdomen, and prostate cancers were examined. The Shapiro-Wilk test was used to evaluate the normality of data grouped by the treatment sites and the DQA methods. The confidence limit coefficients in cases of the normal distribution, and the two-sided Student's t distribution were applied to determine the confidence limits for the grouped data. The Spearman's test was applied to assess the sensitivity of DQA results within the limited groups. The differences in CLs between the two confidence coefficients based on the normal and t-distributions were negligible for the point-dose data and the gamma passing rates with 3%/3 mm criteria. However, with 2%/2 mm criteria, the difference in CLs were 1.6% and 2.2% for composite and per field measurements, respectively. This resulted from the large standard deviation and the more sensitive criteria of 2%/2 mm. There was no noticeable correlation among the different QA methods. Our multi-institutional study suggested that the CL was not a suitable metric for defining the tolerance level when the statistics of the sample group did not follow the normality and had a large standard deviation. PMID- 26894333 TI - Treatment optimization with concurrent SBRT and intracavitary brachytherapy for locally advanced cervical cancer. AB - This work is aimed at investigating treatment planning strategies to optimally com-bine stereotactic body radiation therapy (SBRT) with intracavitary brachytherapy (ICBT) for the treatment of locally advanced cervical cancer. Forty patients (stage IIB - IIIB) previously treated with combined SBRT and ICBT were randomly selected for this retrospective study. All patients were CT- and MR scanned with a ring applicator in situ. HR-CTV and OARs were contoured according to fused CT and MR images. Several ICBT plans were generated for each patient based on different dose prescription points, and then a matching SBRT plan was generated for each ICBT plan. The dose distribution of each composite plan was analyzed with a focus on the doses received by 90% and 100% of the target volume (D90 and D100), the target volume receiving 100% of the prescription dose (V100%), and the doses received by 2 cc and 40% of the OARs (D2 cc and D40). As the distance, d, between the prescription point and the tandem varied within 1.0 and 1.9 cm, the D90, D100 and V100% for the target, as well as D2 cc and D40 for the bladder and rectum approached their optimal values for d value between 1.0 and 1.4 cm. When design-ing a combined ICBT + SBRT plan, one should measure the size of the cervix and set the prescription isodose line 1.0 to 1.4 cm away from the tandem for the ICBT plan first and then optimize the SBRT plan based on the ICBT dose distribution to achieve the best target coverage and critical structures sparing. PMID- 26894334 TI - Moving stereotactic fiducial system to obtain a respiratory signal: proof of principle. AB - The purpose of this study was to obtain a respiratory signal with the use of an add-on device to a specific stereotactic body frame and evaluate precision and accuracy of the method, with the use of a dynamic phantom. The authors designed and constructed a simple add-on device which, attached to a stereotactic body frame, provides information of the patient's respiratory signal in every CT axial image acquired. To assess the approach, 12 CT studies were acquired, on a phantom that simulates respiratory motion, which was placed inside the frame with the add on device. Images of the phantom with sinusoidal and shark-fin motion patterns were acquired, with different amplitude in the movement of the external surrogate and the target. Cycle time was 6 s. Images were retrospectively processed to obtain a respiratory signal from the vertical movement of the "abdomen." The obtained signal was adjusted to a sinusoidal function; the resultant amplitude and cycle time were compared with the preset function in the phantom. The cycle amplitude and time obtained with the method agreed with the preset values within 0.4 mm and 0.29 s, respectively. In the cases of sinusoidal movements the maximal discrepancy was less than 1 mm. A respiratory signal was obtained in all cine CT sequence studies with this method that consistently coincides with the preset motion of the phantom. The authors proposed a tool to obtain a respiratory signal based on information contained into the CT axial images. PMID- 26894335 TI - Comparison of volumetric-modulated arc therapy and dynamic conformal arc treatment planning for cranial stereotactic radiosurgery. AB - The aim was to analyze arc therapy techniques according to the number and position of the brain lesions reported by comparing dynamic noncoplanar conformal arcs (DCA), two coplanar full arcs (RAC) with volumetric-modulated arc therapy (VMAT), multiple noncoplanar partial arcs with VMAT (RANC), and two full arcs with VMAT and 10 degrees table rotation (RAT). Patients with a single lesion (n= 10), multiple lesions (n = 10) or a single lesion close to organs at risk (n = 5) and previously treated with DCA were selected. For each patient, the DCA treatment was replanned with all VMAT techniques. All DCA plans were compared with VMAT plans and evaluated in regard to the different quality indices and dosimetric parameters. For single lesion, homogeneity index (HI) better results were found for the RANC technique (0.17 +/- 0.05) compared with DCA procedure (0.27+/- 0.05). Concerning conformity index (CI), the RAT technique gave higher and better values (0.85 +/- 0.04) compared with those obtained with the DCA technique (0.77 +/- 0.05). DCA improved healthy brain protection (8.35 +/- 5.61 cc vs. 10.52 +/- 6.40 cc for RANC) and reduced monitor unit numbers (3046 +/- 374 MU vs. 4651 +/- 736 for RANC), even if global room occupation was higher. For multiple lesions, VMAT techniques provided better HI (0.16) than DCA (0.24 +/- 0.07). The CI was improved with RAT (0.8 +/- 0.08 for RAT vs. 0.71 +/- 0.08 for DCA). The V10Gy healthy brain was better protected with DCA (9.27 +/- 4.57 cc). Regarding the MU numbers: RANC < RAT< RAC < DCA. For a single lesion close to OAR, RAT achieved high degrees of homogeneity (0.27 +/- 0.03 vs. 0.53 +/- 0.2 for DCA) and conformity (0.72+/- 0.06vs. 0.56 +/- 0.13 for DCA) while sparing organs at risk (Dmax = 12.36 +/- 1.05Gyvs. 14.12 +/- 0.59 Gy for DCA, and Dmean = 3.96 +/- 3.57Gyvs. 4.72 +/- 3.28Gy for DCA). On the other hand, MU numbers were lower with DCA (2254 +/- 190 MUvs. 3438 +/- 457 MU for RANC) even if overall time was inferior with RAC. For a single lesion, DCA provide better plan considering low doses to healthy brain even if quality indexes are better for the others techniques. For multiple lesions, RANC seems to be the best compromise, due to the ability to deliver a good conformity and homogeneity plan while sparing healthy brain tissue. For a single lesion close to organs at risk, RAT is the most appropriate technique. PMID- 26894336 TI - Dosimetric effects of positioning shifts using 6D-frameless stereotactic Brainlab system in hypofractionated intracranial radiotherapy. AB - Dosimetric consequences of positional shifts were studied using frameless Brainlab ExacTrac X-ray system for hypofractionated (3 or 5 fractions) intracranial stereo-tactic radiotherapy (SRT). SRT treatments of 17 patients with metastatic intracranial tumors using the stereotactic system were retrospectively investigated. The treatments were simulated in a treatment planning system by modifying planning parameters with a matrix conversion technique based on positional shifts for initial infrared (IR)-based setup (XC: X-ray correction) and post-correction (XV: X-ray verification). The simulation was implemented with (a) 3D translational shifts only and (b) 6D translational and rotational shifts for dosimetric effects of angular correction. Mean translations and rotations (+/ 1 SD) of 77 fractions based on the initial IR setup (XC) were 0.51 +/- 0.86 mm (lateral), 0.30 +/- 1.55 mm (longitudinal), and -1.63 +/- 1.00 mm (vertical); 0.53 degrees +/- 0.56 degrees (pitch), 0.42 degrees +/- 0.60 degrees (roll), and 0.44 degrees +/- 0.90 degrees (yaw), respectively. These were -0.07 +/- 0.24 mm, -0.07 +/- 0.25 mm, 0.06+/- 0.21 mm, 0.04 degrees +/- 0.23 degrees , 0.00 degrees +/- 0.30 degrees , and -0.02 degrees +/- 0.22 degrees , respectively, for the postcorrection (XV). Substantial degradation of the treatment plans was observed in D95 of PTV (2.6% +/- 3.3%; simulated treatment versus treatment planning), Dmin of PTV (13.4% +/- 11.6%), and Dmin of CTV (2.8% +/- 3.8%, with the maximum error of 10.0%) from XC, while dosimetrically negligible changes (< 0.1%) were detected for both CTV and PTV from XV simulation. 3D angular correction significantly improved CTV dose coverage when the total angular shifts (|pitch| + |roll| + |yaw|) were greater than 2 degrees . With the 6D stereoscopic X-ray verification imaging and frameless immobilization, submillimeter and subdegree accuracy is achieved with negligible dosimetric deviations. 3D angular correction is required when the angular deviation is substantial. A CTV-to-PTV safety margin of 2 mm is large enough to prevent deterioration of CTV coverage. PMID- 26894337 TI - Feasibility of portal dosimetry for flattening filter-free radiotherapy. AB - The feasibility of using portal dosimetry (PD) to verify 6 MV flattening filter free (FFF) IMRT treatments was investigated. An Elekta Synergy linear accelerator with an Agility collimator capable of delivering FFF beams and a standard iViewGT amorphous silicon (aSi) EPID panel (RID 1640 AL5P) at a fixed SSD of 160 cm were used. Dose rates for FFF beams are up to four times higher than for conventional flattened beams, meaning images taken at maximum FFF dose rate can saturate the EPID. A dose rate of 800 MU/min was found not to saturate the EPID for open fields. This dose rate was subsequently used to characterize the EPID for FFF portal dosimetry. A range of open and phantom fields were measured with both an ion chamber and the EPID, to allow comparison between the two. The measured data were then used to create a model within The Nederlands Kanker Instituut's (NKI's) portal dosimetry software. The model was verified using simple square fields with a range of field sizes and phantom thicknesses. These were compared to calculations performed with the Monaco treatment planning system (TPS) and isocentric ion chamber measurements. It was found that the results for the FFF verification were similar to those for flattened beams with testing on square fields, indicating a difference in dose between the TPS and portal dosimetry of approximately 1%. Two FFF IMRT plans (prostate and lung SABR) were delivered to a homogeneous phantom and showed an overall dose difference at isocenter of ~0.5% and good agreement between the TPS and PD dose distributions. The feasibility of using the NKI software without any modifications for high-dose-rate FFF beams and using a standard EPID detector has been investigated and some initial limitations highlighted. PMID- 26894338 TI - Soft tissue and water substitutes for megavoltage photon beams: An EGSnrc-based evaluation. AB - In this work, soft-tissue equivalence of water, polystyrene, PMMA and water equivalence of polystyrene, and PMMA has been assessed for multiple megavoltage photon beams and field sizes. EGSnrc based Monte Carlo (MC) codes, BEAMnrc and DOSXYZnrc are used for the linac head modeling and the phantom dose calculations, respectively. Percentage depth doses (PDDs) are scored for two field sizes (5 * 5 cm2, 10 * 10 cm2) and photon energies (6 MV and 10 MV) in water, polystyrene, PMMA, and soft tissue. The comparisons of PDDs show that soft-tissue equivalence of various materials varies with the depth in the phantom, field size, and photon energy. Water and PMMA are found to be the closest soft-tissue and water substitutes, respectively. Soft-tissue and water equivalence of dosimetry materials need to be evaluated for a range of photon energies and field sizes before their application in complex radiation beams. PMID- 26894339 TI - Radiation intensity (CTDIvol) and visibility of anatomical structures in head CT examinations. AB - The purpose of this study was to quantify how changing the amount of radiation used to perform routine head CT examinations (CTDIvol) affects visibility of key anatomical structures. Eight routine noncontrast head CT exams were selected from six CT scanners, each of which had a different CTDIvol setting (60 to 75 mGy). All exams were normal and two slices were selected for evaluation, one at the level of basal ganglia and the other at the fourth ventricle. Three experienced neuroradiologists evaluated the visibility of selected structures, including the putamen, caudate nucleus, thalamus, internal capsule, grey/white differentiation, and brainstem. Images were scored on a five-point scoring scheme (1, unacceptable, 3, satisfactory, and 5, excellent). Reader scores, averaged over the cases obtained from each scanner, were plotted as a function of the corresponding CTDIvol. Average scores for the fourth ventricle were 3.06 +/- 0.83 and for the basal ganglia were 3.20 +/- 0.86. No image received a score of 1. Two readers showed no clear trend of an increasing score with increasing CTDIvol. One reader showed a slight trend of increasing score with increasing CTDIvol, but the increase in score from a 25% increase in CTDIvol was a fraction of the standard deviation associated average scores. Collectively, results indicated that there were no clear improvements in visualizing neuroanatomy when CTDIvol increased from 60 to 75 mGy in routine head CT examinations. Our study showed no apparent benefit of using more than 60 mGy when performing routine noncontrast head CT examinations. PMID- 26894340 TI - The impact of spectral filtration on image quality in micro-CT system. AB - This paper aims to evaluate the impact of spectral filtration on image quality in a microcomputed tomography (micro-CT) system. A mouse phantom comprising 11rods for modeling lung, muscle, adipose, and bones was scanned with 17 s and 2min, respectively. The current (MUA) for each scan was adjusted to achieve identical entrance exposure to the phantom, providing a baseline for image quality evaluation. For each region of interest (ROI) within specific composition, CT number variations, noise levels, and contrast-to-noise ratios (CNRs) were evaluated from the reconstructed images. CT number variations and CNRs for bone with high density, muscle, and adipose were compared with theoretical predictions. The results show that the impact of spectral filtration on image quality indicators, such as CNR in a micro-CT system, is significantly associated with tissue characteristics. The findings may provide useful references for optimizing the scanning parameters of general micro-CT systems in future imaging applications. PMID- 26894341 TI - Gafchromic XR-QA2 film as a complementary dosimeter for hand-monitoring in CTF guided biopsies. AB - Computed tomography fluoroscopy (CTF) is a useful imaging technique to guide biopsies, particularly lung biopsies, but it also has the potential for very high hand exposures, despite use of quick-check method and needle holders whenever feasible. Therefore, reliable monitoring is crucial to ensure the safe use of CTF. This is a challenge, because ring dosimeters monitor exposure only at the base of one finger, while the fingertips may be exposed to the highly collimated CT beam. In this work we have explored the possibility of using Gafchromic XR-QA2 self-developing film as a complementary dosimeter to quantify hand exposure during CTF-guided biopsies. A glove used in a previous study and designed to contain 11 TLDs was adapted to include Gafchromic strips 7 mm wide, covering the fingers. A total of 22 biopsies were successfully performed wearing this GafTLD glove under sterile gloves, and the IR reported no difficulty or reduction of dexterity while wearing it. Comparison of dose distributions obtained from digitization of the Gafchromic film strips and absolute Hp(0.07) readings from TLDs showed good agreement, despite some positional uncertainty due to relative movement. Per procedure, doses at the base of the ring finger can be as low as 3% 8% of hand dose maximum. Accumulated dose at the base of the ring finger was four times lower than the dose maximum. PMID- 26894342 TI - Clinical implementation of multisequence MRI-based adaptive intracavitary brachytherapy for cervix cancer. AB - The purpose of this study was to describe the clinical implementation of a magnetic resonance image (MRI)-based approach for adaptive intracavitary brachytherapy (ICBT) of cervix cancer patients. Patients were implanted with titanium tandem and colpostats. MR imaging was performed on a 1.5-T Philips scanner using T2-weighted (T2W), proton-density weighted (PDW), and diffusion weighted (DW) imaging sequences. Apparent diffusion coefficient (ADC) maps were generated from the DW images. All images were fused. T2W images were used for the definition of organs at risk (OARs) and dose points. ADC maps in conjunction with T2W images were used for target delineation. PDW images were used for applicator definition. Forward treatment planning was performed using standard source distribution rules normalized to Point A. Point doses and dose-volume parameters for the tumor and OARs were exported to an automated dose-tracking application. Brachytherapy doses were adapted for tumor shrinkage and OAR variations during the course of therapy. The MRI-based ICBT approach described here has been clinically implemented and is carried out for each brachytherapy fraction. Total procedure time from patient preparation to delivery of treatment is typically 2 hrs. Implementation of our tech-nique for structure delineation, applicator definition, dose tracking, and adaptation is demonstrated using treated patient examples. Based on published recommendations and our clinical experience in the radiation treatment of cervix cancer patients, we have refined our standard approach to ICBT by 1) incorporating a multisequence MRI technique for improved visualization of the target, OARs, and applicator, and by 2) implementing dose adaptation by use of automated dose tracking tools. PMID- 26894343 TI - Optimal unified combination rule in application of Dempster-Shafer theory to lung cancer radiotherapy dose response outcome analysis. AB - Our previous study demonstrated the application of the Dempster-Shafer theory of evidence to dose/volume/outcome data analysis. Specifically, it provided Yager's rule to fuse data from different institutions pertaining to radiotherapy pneumonitis versus mean lung dose. The present work is a follow-on study that employs the optimal unified combination rule, which optimizes data similarity among independent sources. Specifically, we construct belief and plausibility functions on the lung cancer radiotherapy dose outcome datasets, and then apply the optimal unified combination rule to obtain combined belief and plausibility, which bound the probabilities of pneumonitis incidence. To estimate the incidence of pneumonitis at any value of mean lung dose, we use the Lyman-Kutcher-Burman (LKB) model to fit the combined belief and plausibility curves. The results show that the optimal unified combination rule yields a narrower uncertainty range (as represented by the belief-plausibility range) than Yager's rule, which is also theoretically proven. PMID- 26894344 TI - Size-based protocol optimization using automatic tube current modulation and automatic kV selection in computed tomography. AB - Size-based diagnostic reference ranges (DRRs) for contrast-enhanced pediatric abdominal computed tomography (CT) have been published in order to establish practical upper and lower limits of CTDI, DLP, and SSDE. Based on these DRRs, guidelines for establishing size-based SSDE target levels from the SSDE of a standard adult by applying a linear correction factor have been published and provide a great reference for dose optimization initiatives. The necessary step of designing manufacturer-specific CT protocols to achieve established SSDE targets is the responsibility of the Qualified Medical Physicist. The task is straightforward if fixed-mA protocols are used, however, more difficult when automatic exposure control (AEC) and automatic kV selection are considered. In such cases, the physicist must deduce the operation of AEC algorithms from technical documentation or through testing, using a wide range of phantom sizes. Our study presents the results of such testing using anthropomorphic phantoms ranging in size from the newborn to the obese adult. The effect of each user controlled parameter was modeled for a single-manufacturer AEC algorithm (Siemens CARE Dose4D) and automatic kV selection algorithm (Siemens CARE kV). Based on the results presented in this study, a process for designing mA-modulated, pediatric abdominal CT protocols that achieve user-defined SSDE and kV targets is described. PMID- 26894345 TI - Percentage depth dose calculation accuracy of model based algorithms in high energy photon small fields through heterogeneous media and comparison with plastic scintillator dosimetry. AB - Small fields smaller than 4 * 4 cm2 are used in stereotactic and conformal treatments where heterogeneity is normally present. Since dose calculation accuracy in both small fields and heterogeneity often involves more discrepancy, algorithms used by treatment planning systems (TPS) should be evaluated for achieving better treatment results. This report aims at evaluating accuracy of four model-based algorithms, X-ray Voxel Monte Carlo (XVMC) from Monaco, Superposition (SP) from CMS-Xio, AcurosXB (AXB) and analytical anisotropic algorithm (AAA) from Eclipse are tested against the measurement. Measurements are done using Exradin W1 plastic scintillator in Solid Water phantom with heterogeneities like air, lung, bone, and aluminum, irradiated with 6 and 15 MV photons of square field size ranging from 1 to 4 cm2. Each heterogeneity is introduced individually at two different depths from depth-of-dose maximum (Dmax), one setup being nearer and another farther from the Dmax. The central axis percentage depth-dose (CADD) curve for each setup is measured separately and compared with the TPS algorithm calculated for the same setup. The percentage normalized root mean squared deviation (%NRMSD) is calculated, which represents the whole CADD curve's deviation against the measured. It is found that for air and lung heterogeneity, for both 6 and 15 MV, all algorithms show maximum deviation for field size 1 * 1 cm2 and gradually reduce when field size increases, except for AAA. For aluminum and bone, all algorithms' deviations are less for 15 MV irrespective of setup. In all heterogeneity setups, 1 * 1 cm2 field showed maximum deviation, except in 6MV bone setup. All algorithms in the study, irrespective of energy and field size, when any heterogeneity is nearer to Dmax, the dose deviation is higher compared to the same heterogeneity far from the Dmax. Also, all algorithms show maximum deviation in lower-density materials compared to high-density materials. PMID- 26894346 TI - Evaluation of MVCT imaging dose levels during helical IGRT: comparison between ion chamber, TLD, and EBT3 films. AB - The purpose of this investigation was to evaluate the dose on megavoltage CT (MVCT) images required for tomotherapy. As imaging possibilities are often used before each treatment and usually used several times before the session, we tried to evaluate the dose delivered during the procedure. For each scanning mode (fine, normal, and coarse), we first established the relative variation of these doses according to different technical parameters (explored length, patient setup). These dose variations measured with the TomoPhant, also known as Cheese phantom, showed the expected variations (due to the variation of scattered radiation) of 15% according to the explored length and +/- 5% according to the phantom setup (due to the variation of the point of measurement in the bore). In order to estimate patient doses, an anthropomorphic phantom was used for thermoluminescent and film dosimetry. The degree of agreement between the two methods was very satisfactory (the differences correspond to 5 mGy per imaging session) for the three sites studied (head & neck, thorax, and abdomen). These measurements allowed us to estimate the delivered dose of between 1 cGy and 4 cGy according to the site and imaging mode. Finally, we attempted to investigate a way to calculate this delivered dose in our patients from the study conducted on a cylindrical phantom and by taking into account data from the initial kV-CT scan. The results we obtained were close to our measurements, with discrepancies below 5 mGy per MVCT. PMID- 26894347 TI - Quantification of interplay and gradient effects for lung stereotactic ablative radiotherapy (SABR) treatments. AB - This study quantified the interplay and gradient effects on GTV dose coverage for 3D CRT, dMLC IMRT, and VMAT SABR treatments for target amplitudes of 5-30 mm using 3DVH v3.1 software incorporating 4D Respiratory MotionSim (4D RMS) module. For clinically relevant motion periods (5 s), the interplay effect was small, with deviations in the minimum dose covering the target volume (D99%) of less than +/- 2.5% for target amplitudes up to 30 mm. Increasing the period to 60 s resulted in interplay effects of up to +/- 15.0% on target D99% dose coverage. The gradient effect introduced by target motion resulted in deviations of up to +/- 3.5% in D99% target dose coverage. VMAT treatments showed the largest deviation in dose metrics, which was attributed to the long delivery times in comparison to dMLC IMRT. Retrospective patient analysis indicated minimal interplay and gradient effects for patients treated with dMLC IMRT at the NCCI. PMID- 26894348 TI - Evaluation of commercial extension plates for the ACR CT accreditation phantom. AB - The American College of Radiology (ACR) Computed Tomography (CT) Accreditation Program requires submission of phantom scans acquired with the ACR accreditation phantom. There is a known issue with some wide-beam scanners in which the Hounsfield unit (HU) value of water may be correct when using the scanner manufacturer's phantom, but will be out of range in some scan modes when scanning the accreditation phantom. The phantom manufacturer has developed a product known as Extension Plates to eliminate the water HU value issue. The purpose of this technical note is to evaluate the effectiveness of the Extension Plates in alleviating the water HU issue. The ACR phantom was scanned on nine different CT scanners representing four CT manufacturers at eight different facilities. Scanner models included 16- and 64-channel geometries from each manufacturer. All scanners passed routine daily water HU testing per the manufacturer's instructions. The accreditation phantom was scanned in helical and axial modes both with and without the Extension Plates present. Regions of interest were placed on the linearity test objects as well as the water HU test object in Module 1 of the phantom. Mean values were recorded and compared with the acceptable ranges specified by the ACR accreditation phantom testing instructions. Water HU values failed for one scanner model when scanned in helical mode using the widest collimation available and the Extension Plates were not present. All other scanner models passed the water HU linearity test with or without the Extension Plates in both axial and helical scan modes. Three of the four manufacturers tested failed the linearity test for different materials. The presence of the Extension Plates only affected the HU measurement for the water test object. PMID- 26894349 TI - Approaches to interventional fluoroscopic dose curves. AB - Modern fluoroscopes used for image-based guidance in interventional procedures are complex X-ray machines, with advanced image acquisition and processing systems capable of automatically controlling numerous parameters based on defined protocol settings. This study evaluated and compared approaches to technique factor modulation and air kerma rates in response to simulated patient thickness variations for four state-of-the-art and one previous-generation interventional fluoroscopes. A polymethyl methacrylate (PMMA) phantom was used as a tissue surrogate for the purposes of determining fluoroscopic reference plane air kerma rates, kVp, mA, and variable copper filter thickness over a wide range of simulated tissue thicknesses. Data were acquired for each fluoroscopic and acquisition dose curve within each vendor's default abdomen or body imaging protocol. The data obtained indicated vendor- and model-specific variations in the approach to technique factor modulation and reference plane air kerma rates across a range of tissue thicknesses. However, in the imaging protocol evaluated, all of the state-of-the-art systems had relatively low air kerma rates in the fluoroscopic low-dose imaging mode as compared to the previous-generation unit. Each of the newest-generation systems also employ Cu filtration within the selected protocol in the acquisition mode of imaging; this is a substantial benefit, reducing the skin entrance dose to the patient in the highest dose-rate mode of fluoroscope operation. Some vendors have also enhanced the radiation output capabilities of their fluoroscopes which, under specific conditions, may be beneficial; however, these increased output capabilities also have the potential to lead to unnecessarily high dose rates. Understanding how fluoroscopic technique factors are modulated provides insight into the vendor specific image acquisition approach and may provide opportunities to optimize the imaging protocols for clinical practice. PMID- 26894350 TI - On the selection of gantry and collimator angles for isocenter localization using Winston-Lutz tests. AB - In Winston-Lutz (WL) tests, the isocenter of a linear accelerator (linac) is determined as the intersection of radiation central axes (CAX) from multiple gantry, collimator, and couch angles. It is well known that the CAX can wobble due to mechanical imperfections of the linac. Previous studies suggested that the wobble varies with gantry and collimator angles. Therefore, the isocenter determined in the WL tests has a profound dependence on the gantry and collimator angles at which CAX are sampled. In this study, we evaluated the systematic and random errors in the iso-centers determined with different CAX sampling schemes. Digital WL tests were performed on six linacs. For each WL test, 63 CAX were sampled at nine gantry angles and seven collimator angles. Subsets of these data were used to simulate the effects of various CAX sampling schemes. An isocenter was calculated from each subset of CAX and compared against the reference isocenter, which was calculated from 48 opposing CAX. The differences between the calculated isocenters and the reference isocenters ranged from 0 to 0.8 mm. The differences diminished to less than 0.2 mm when 24 or more CAX were sampled. Isocenters determined with collimator 0 degrees were vertically lower than those determined with collimator 90 degrees and 270 degrees . Isocenter localization errors in the longitudinal direction (along the axis of gantry rotation) showed a strong dependence on the collimator angle selected. The errors in all directions were significantly reduced when opposing collimator angles and opposing gantry angles were employed. The isocenter localization errors were less than 0.2 mm with the common CAX sampling scheme, which used four cardinal gantry angles and two opposing collimator angles. Reproducibility stud-ies on one linac showed that the mean and maximum variations of CAX during the WL tests were 0.053 mm and 0.30 mm, respectively. The maximal variation in the resulting isocenters was 0.068 mm if 48 CAX were used, or 0.13 mm if four CAX were used. Quantitative results from this study are useful for understanding and minimizing the isocenter uncertainty in WL tests. PMID- 26894351 TI - Commissioning an Elekta Versa HD linear accelerator. AB - The purpose of this study is to report the dosimetric aspects of commissioning performed on an Elekta Versa HD linear accelerator (linac) with high-dose-rate flattening filter-free (FFF) photon modes and electron modes. Acceptance and commissioning was performed on the Elekta Versa HD linac with five photon energies (6 MV, 10 MV, 18 MV, 6 MV FFF, 10 MV FFF), four electron energies (6 MeV, 9MeV, 12 MeV, 15 MeV) and 160-leaf (5 mm wide) multileaf collimators (MLCs). Mechanical and dosimetric data were measured and evaluated. The measurements include percent depth doses (PDDs), in-plane and cross-plane profiles, head scatter factor (Sc), relative photon output factors (Scp), universal wedge transmission factor, MLC transmission factors, and electron cone factors. Gantry, collimator, and couch isocentricity measurements were within 1 mm, 0.7 mm, and 0.7 mm diameter, respectively. The PDDs of 6 MV FFF and 10 MV FFF beams show deeper dmax and steeper falloff with depth than the corresponding flattened beams. While flatness values of 6 MV FFF and 10 MV FFF normalized profiles were expectedly higher than the corresponding flattened beams, the symmetry values were almost identical. The cross-plane penumbra values were higher than the in plane penumbra values for all the energies. The MLC transmission values were 0.5%, 0.6%, and 0.6% for 6 MV, 10 MV, and 18 MV photon beams, respectively. The electron PDDs, profiles, and cone factors agree well with the literature. The outcome of radiation treatment is directly related to the accuracy in the dose modeled in the treatment planning system, which is based on the commissioned data. Commissioning data provided us a valuable insight into the dosimetric characteristics of the beam. This set of commissioning data can provide comparison data to others performing Versa HD commissioning, thereby improving patient safety. PMID- 26894352 TI - Pinnacle3 modeling and end-to-end dosimetric testing of a Versa HD linear accelerator with the Agility head and flattening filter-free modes. AB - The Elekta Versa HD incorporates a variety of upgrades to the line of Elekta linear accelerators, primarily including the Agility head and flattening filter free (FFF) photon beam delivery. The completely distinct dosimetric output of the head from its predecessors, combined with the FFF beams, requires a new investigation of modeling in treatment planning systems. A model was created in Pinnacle3 v9.8 with the commissioned beam data. A phantom consisting of several plastic water and Styrofoam slabs was scanned and imported into Pinnacle3, where beams of different field sizes, source-to-surface distances (SSDs), wedges, and gantry angles were devised. Beams included all of the available photon energies (6, 10, 18, 6FFF, and 10 FFF MV), as well as the four electron energies commissioned for clinical use (6, 9, 12, and 15 MeV). The plans were verified at calculation points by measurement with a calibrated ionization chamber. Homogeneous and hetero-geneous point-dose measurements agreed within 2% relative to maximum dose for all photon and electron beams. AP photon open field measurements along the central axis at 100 cm SSD passed within 1%. In addition, IMRT testing was also performed with three standard plans (step and shoot IMRT, as well as a small- and large-field VMAT plan). The IMRT plans were delivered on the Delta4 IMRT QA phantom, for which a gamma passing rate was > 99.5% for all plans with a 3% dose deviation, 3 mm distance-to-agreement, and 10% dose threshold. The IMRT QA results for the first 23 patients yielded gamma passing rates of 97.4% +/- 2.3%. Such testing ensures confidence in the ability of Pinnacle3 to model photon and electron beams with the Agility head. PMID- 26894353 TI - Implementation of an in-house visual feedback system for motion management during radiation therapy. AB - In this Technical Note, we describe an in-house video goggles feedback system assembled using several commercially available products. This goggle video feed back system is currently being used at University of Louisville and Mayo Clinic for both CT simulation and linac treatment delivery. The setup details, including specific recommendations, are provided, along with an alternative option for using the video goggles system. PMID- 26894354 TI - Quantification of dental prostheses on cone-beam CT images by the Taguchi method. AB - The gray values accuracy of dental cone-beam computed tomography (CBCT) is affected by dental metal prostheses. The distortion of dental CBCT gray values could lead to inaccuracies of orthodontic and implant treatment. The aim of this study was to quantify the effect of scanning parameters and dental metal prostheses on the accuracy of dental cone-beam computed tomography (CBCT) gray values using the Taguchi method. Eight dental model casts of an upper jaw including prostheses, and a ninth prosthesis-free dental model cast, were scanned by two dental CBCT devices. The mean gray value of the selected circular regions of interest (ROIs) were measured using dental CBCT images of eight dental model casts and were compared with those measured from CBCT images of the prosthesis free dental model cast. For each image set, four consecutive slices of gingiva were selected. The seven factors (CBCTs, occlusal plane canting, implant connection, prosthesis position, coping material, coping thickness, and types of dental restoration) were used to evaluate scanning parameter and dental prostheses effects. Statistical methods of signal to noise ratio (S/N) and analysis of variance (ANOVA) with 95% confidence were applied to quantify the effects of scanning parameters and dental prostheses on dental CBCT gray values accuracy. For ROIs surrounding dental prostheses, the accuracy of CBCT gray values were affected primarily by implant connection (42%), followed by type of restoration (29%), prostheses position (19%), coping material (4%), and coping thickness (4%). For a single crown prosthesis (without support of implants) placed in dental model casts, gray value differences for ROIs 1-9 were below 12% and gray value differences for ROIs 13-18 away from pros-theses were below 10%. We found the gray value differences set to be between 7% and 8% for regions next to a single implant-supported titanium prosthesis, and between 46% and 59% for regions between double implant-supported, nickel-chromium alloys (Ni-Cr) prostheses. Quantification of the effect of prostheses and scanning parameters on dental CBCT gray values was assessed. PMID- 26894355 TI - A specially designed domed-cones template for needles (seeds) fixation and incline insertion in prostate implant brachytherapy. AB - The construction of a conventional prostate needle (seeds) implant template restricts needles tilting or incline insertion when it is necessary to approach a seminal vesicle or to avoid the obstruction of symphysis pubis. To overcome the disadvantages of conventional templates, we developed a special template for guiding needles incline insertion and fixation for prostate needle implant. Phantom needles implantation was performed. Two acrylic boards, each 7.5 cm in width by 7.5 cm in length and 0.5 cm thickness, were drilled with a set of domed holes and cones with embedded template ball inside this combination to provide firm grip and fixation in prostate needle implantation. The specially designed domed-cones combination acrylic board provides a needle of up to 60 degrees rotation flexibility application. Some areas that could not be covered in a conventional parallel needle holes template could now be covered by using this new template. The covering index of prostate radiation dosage is up to 84.5%. The specially designed domed-cones acrylic board combination provides not only a reliable means of needle fixation and rotational function, but also a superior dose distribution in the anterior portion of the prostate and good coverage of a seminal vesicle. This special template is a feasible design for prostate needles or seeds implant brachytherapy. PMID- 26894356 TI - An algorithm for automated ROI definition in water or epoxy-filled NEMA NU-2 image quality phantoms. AB - Drawing regions of interest (ROIs) in positron emission tomography/computed tomography (PET/CT) scans of the National Electrical Manufacturers Association (NEMA) NU-2 Image Quality (IQ) phantom is a time-consuming process that allows for interuser variability in the measurements. In order to reduce operator effort and allow batch processing of IQ phantom images, we propose a fast, robust, automated algorithm for performing IQ phantom sphere localization and analysis. The algorithm is easily altered to accommodate different configurations of the IQ phantom. The proposed algorithm uses information from both the PET and CT image volumes in order to overcome the challenges of detecting the smallest spheres in the PET volume. This algorithm has been released as an open-source plug-in to the Osirix medical image viewing software package. We test the algorithm under various noise conditions, positions within the scanner, air bubbles in the phantom spheres, and scanner misalignment conditions. The proposed algorithm shows run-times between 3 and 4 min and has proven to be robust under all tested conditions, with expected sphere localization deviations of less than 0.2 mm and variations of PET ROI mean and maximum values on the order of 0.5% and 2%, respectively, over multiple PET acquisitions. We conclude that the proposed algorithm is stable when challenged with a variety of physical and imaging anomalies, and that the algorithm can be a valuable tool for those who use the NEMA NU-2 IQ phantom for PET/CT scanner acceptance testing and QA/QC. PMID- 26894357 TI - Patient dose measurement in common medical X-ray examinations in Iran. AB - The main purpose of this study was to investigate patient dose in the chest (PA/AP/LAT) and skull (PA/AP/LAT) X-ray examinations, as frequent procedures. The study was performed in eight public hospitals of Khuzestan province, Iran. Patient dosimetry was conducted on 567 standard patient X-ray examinations (males: 61.2%, female: 38.2%). Dosimetry protocol in this study was indirect method, according to the International Atomic Energy Agency (IAEA) Technical Reports series No.457. Patients weighing 70 +/- 10 kg were considered as standard. In the indirect dosimetry approach, exposure parameters such as kVp, mAs, focal film distance (FFD), and tube outputs recorded during data acquisition were used for calculating incident air kerma on the patient's skin, entrance surface air kerma (ESAK) that is recommended by the IAEA as the most appropriate patient dosimetry quantity in simple radiographic examinations. This survey reveals significant variations in the radiological practice. Results showed that the parameters set by radiologic technologists change in a wide range: mAs varied from 2 to 80 for skull PA, 2 to 202 for chest LAT, and FFD varied from 50 to 180 for skull LAT projection. The study showed that patient doses in three chest projections exceed the IAEA and European Commission dose reference levels (EC DRLs) - 1.0, 1.12, and 2.20 mGy for chest PA, chest AP, and chest LAT, respectively. Results also showed that mean ESAKs of patients in skull projections were generally lower than the IAEA and EC DRLs, 1.5, 1.72, and 2.25 for skull LAT, skull AP, and skull PA, respectively. This study provides evidence that dose reduction in the simple X-ray examinations is feasible by updating clinical audits and implementation of systematic quality assurance (QA) and quality control (QC) programs. The authors recommend that DRLs obtained in this study can be used as local DRLs in Khuzestan area and dose surveys must be performed in all provinces to establish national dose reference levels (NDRLs) in Iran. PMID- 26894358 TI - Optimum location of external markers using feature selection algorithms for real time tumor tracking in external-beam radiotherapy: a virtual phantom study. AB - In external-beam radiotherapy, using external markers is one of the most reliable tools to predict tumor position, in clinical applications. The main challenge in this approach is tumor motion tracking with highest accuracy that depends heavily on external markers location, and this issue is the objective of this study. Four commercially available feature selection algorithms entitled 1) Correlation-based Feature Selection, 2) Classifier, 3) Principal Components, and 4) Relief were proposed to find optimum location of external markers in combination with two "Genetic" and "Ranker" searching procedures. The performance of these algorithms has been evaluated using four-dimensional extended cardiac-torso anthropomorphic phantom. Six tumors in lung, three tumors in liver, and 49 points on the thorax surface were taken into account to simulate internal and external motions, respectively. The root mean square error of an adaptive neuro-fuzzy inference system (ANFIS) as prediction model was considered as metric for quantitatively evaluating the performance of proposed feature selection algorithms. To do this, the thorax surface region was divided into nine smaller segments and predefined tumors motion was predicted by ANFIS using external motion data of given markers at each small segment, separately. Our comparative results showed that all feature selection algorithms can reasonably select specific external markers from those segments where the root mean square error of the ANFIS model is minimum. Moreover, the performance accuracy of proposed feature selection algorithms was compared, separately. For this, each tumor motion was predicted using motion data of those external markers selected by each feature selection algorithm. Duncan statistical test, followed by F-test, on final results reflected that all proposed feature selection algorithms have the same performance accuracy for lung tumors. But for liver tumors, a correlation-based feature selection algorithm, in combination with a genetic search algorithm, proved to yield best performance accuracy for selecting optimum markers. PMID- 26894359 TI - Dosimetric impact of dental metallic crown on intensity-modulated radiotherapy and volumetric-modulated arc therapy for head and neck cancer. AB - Metal dental restoration materials cause dose enhancement upstream and dose disturbance downstream of the high-density inhomogeneous regions in which these materials are used. In this study, we evaluated the impact of a dental metallic crown (DMC) on intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) for head and neck cancer. Additionally, the possibility of sparing the oral mucosa from dose enhancement using an individual intraoral mouthpiece was evaluated. An experimental oral phantom was designed to verify the dosimetric impact of a DMC. We evaluated the effect on single beam, parallel opposing beam, arc beam, IMRT, and VMAT treatment plans. To evaluate the utility of a 3-mm-thick intraoral mouthpiece, the doses across the mouthpiece were measured. For single beam irradiation, the measured doses at the entrance and exit planes of the DMC were 51% higher and 21% lower than the calculated dose by the treatment planning system, respectively. The maximum dose enhancements were 22% and 46% for parallel opposing beams and the 90 degrees arc rotation beam, respectively. For IMRT and VMAT, the measured doses adjacent to the DMC were 12.2% +/- 6.3% (mean +/- 1.96SD) and 12.7% +/- 2.5% higher than the calculated doses, respectively. With regard to the performance of the intraoral mouthpiece for the IMRT and VMAT cases, the disagreement between measured and calculated doses at the outermost surface of the mouthpieces were -2.0%, and 2.0%, respectively. Dose enhancements caused by DMC-mediated radiation scattering occurred during IMRT and VMAT. Because it is difficult to accurately estimate the dose perturbations, careful consideration is necessary when planning head and neck cancer treatments in patients with DMCs. To spare the oral mucosa from dose enhancement, the use of an individual intraoral mouthpiece should be considered. PMID- 26894360 TI - Investigation of optimal display size for viewing T1-weighted MR images of the brain using a digital contrast-detail phantom. AB - We clarified the relationship between the display size of MRI images and observer performance using a digital contrast-detail (d-CD) phantom. The d-CD phantom was developed using Microsoft Visual Basic 2010 Express. It had a 512 * 512 matrix in size and a total of 100 holes, whose diameter increased stepwise from 4 to 40 pixels with a 4-pixel interval in the vertical direction; the contrast varied stepwise in the horizontal direction. The digital driving level (DDL) of the back ground, the width of the DDL, and the contrast were adjustable. These parameters were determined on the basis of the actual T1-weighted magnetic resonance (MR) images of the brain. In this study, the DDL, width, and contrast were set to 85, 20, and 1, respectively. The observer performance study was performed for three different display sizes (30 cm * 30 cm as the enlarged size, 16 cm * 16 cm as the original size, and 10 cm * 10 cm as the reduced size) using a 2-megapixel color liquid crystal display monitor, and it was analyzed using Friedman and Wilcoxon statistical tests. The observer performances for the original display (p < 0.01) and the reduced display sizes (p < 0.01) were superior to that observed for the enlarged size, whereas there was no significant difference between the original display and reduced display sizes (p = 0.31). Evaluation with the digital phantom simulating MR imaging also revealed that the original and reduced display sizes were superior to the enlarged display size in observer performance. The d-CD phantom enables a short-term evaluation of observer performance and is useful in analyzing relation-ship between display size and observer performance. PMID- 26894361 TI - Evaluation of fluence-based dose delivery incorporating the spatial variation of dosimetric leaf gap (DLG). AB - The Eclipse treatment planning system uses a single dosimetric leaf gap (DLG) value to retract all multileaf collimator leaf positions during dose calculation to model the rounded leaf ends. This study evaluates the dosimetric impact of the 2D variation of DLG on clinical treatment plans based on their degree of fluence modulation. In-house software was developed to retrospectively apply the 2D variation of DLG to 61 clinically treated VMAT plans, as well as to several test plans. The level of modulation of the VMAT cases were determined by calculating their modulation complexity score (MCS). Dose measurements were done using the MapCHECK device at a depth of 5.0 cm for plans with and without the 2D DLG correction. Measurements were compared against predicted dose planes from the TPS using absolute 3%/3 mm and 2%/2 mm gamma criteria for test plans and for VMAT cases, respectively. The gamma pass rate for the 2 mm, 4 mm, and 6 mm sweep test plans increased by 23.2%, 28.7%, and 26.0%, respectively, when the measurements were corrected with 2D variation of DLG. The clinical anal VMAT cases, which had very high MLC modulation, showed the most improvement. The majority of the improvement occurred for doses created by the 1.0 cm width leaves for both the test plans and the VMAT cases. The gamma pass rates for the highly modulated head and neck (H&N) cases, moderately modulated prostate and esophageal cases, and minimally modulated brain cases improved only slightly when corrected with 2D variation of DLG. This is because these cases did not employ the 1.0 cm width leaves for dose calculation and delivery. These data suggest that, at the very least, the TPS plans with highly modulated fluences created by the 1.0 cm fields require 2D DLG correction. Incorporating the 2D variation of DLG for the highly modulated clinical treatment plans improves their planar dose gamma pass rates, especially for fields employing the outer 1.0 cm width MLC leaves. This is because there are differences in DLG between the true DLG exhibited by the 1.0 cm width outer leaves and the constant DLG value modeled by the TPS for dose calculation. PMID- 26894362 TI - Learning anatomy changes from patient populations to create artificial CT images for voxel-level validation of deformable image registration. AB - The purpose of this study was to develop an approach to generate artificial computed tomography (CT) images with known deformation by learning the anatomy changes in a patient population for voxel-level validation of deformable image registration. Using a dataset of CT images representing anatomy changes during the course of radiation therapy, we selected a reference image and registered the remaining images to it, either directly or indirectly, using deformable registration. The resulting deformation vector fields (DVFs) represented the anatomy variations in that patient population. The mean deformation, computed from the DVFs, and the most prominent variations, which were captured using principal component analysis (PCA), composed an active shape model that could generate random known deformations with realistic anatomy changes based on those learned from the patient population. This approach was applied to a set of 12 head and neck patients who received intensity-modulated radiation therapy for validation. Artificial planning CT and daily CT images were generated to simulate a patient with known anatomy changes over the course of treatment and used to validate the deformable image registration between them. These artificial CT images potentially simulated the actual patients' anatomies and also showed realistic anatomy changes between different daily CT images. They were used to successfully validate deformable image registration applied to intrapatient deformation. PMID- 26894363 TI - Intensity-modulated radiation therapy dose verification using fluence and portal imaging device. AB - Patient-specific quality assurance for intensity-modulated radiation therapy (IMRT) dose verification is essential. The aim of this study is to provide a new method based on the relative error distribution by comparing the fluence map from the treatment planning system (TPS) and the incident fluence deconvolved from the electronic portal imaging device (EPID) images. This method is validated for 10 head and neck IMRT cases. The fluence map of each beam was exported from the TPS and EPID images of the treatment beams were acquired. Measured EPID images were deconvolved to the incident fluence with proper corrections. The relative error distribution between the TPS fluence map and the incident fluence from the EPID was created. This was also created for a 2D diode array detector. The absolute point dose was measured with an ionization chamber, and the dose distribution was measured by a radiochromic film. In three cases, MLC leaf positions were intentionally changed to create the dose error as much as 5% against the planned dose and our fluence-based method was tested using gamma index. Absolute errors between the predicted dose of 2D diode detector and of our method and measurements were 1.26% +/- 0.65% and 0.78% +/- 0.81% respectively. The gamma passing rate (3% global / 3 mm) of the TPS was higher than that of the 2D diode detector (p< 0.02), and lower than that of the EPID (p < 0.04). The gamma passing rate (2% global / 2 mm) of the TPS was higher than that of the 2D diode detector, while the gamma passing rate of the TPS was lower than that of EPID (p < 0.02). For three modified plans, the predicted dose errors against the measured dose were 1.10%, 2.14%, and -0.87%. The predicted dose distributions from the EPID were well matched to the measurements. Our fluence-based method provides very accurate dosimetry for IMRT patients. The method is simple and can be adapted to any clinic for complex cases. PMID- 26894364 TI - Automatic planning of head and neck treatment plans. AB - Treatment planning is time-consuming and the outcome depends on the person performing the optimization. A system that automates treatment planning could potentially reduce the manual time required for optimization and could also provide a method to reduce the variation between persons performing radiation dose planning (dosimetrist) and potentially improve the overall plan quality. This study evaluates the performance of the Auto-Planning module that has recently become clinically available in the Pinnacle3 radiation therapy treatment planning system. Twenty-six clinically delivered head and neck treatment plans were reoptimized with the Auto-Planning module. Comparison of the two types of treatment plans were performed using DVH metrics and a blinded clinical evaluation by two senior radiation oncologists using a scale from one to six. Both evaluations investigated dose coverage of target and dose to healthy tissues. Auto-Planning was able to produce clinically acceptable treatment plans in all 26 cases. Target coverages in the two types of plans were similar, but automatically generated plans had less irradiation of healthy tissue. In 94% of the evaluations, the autoplans scored at least as high as the previously delivered clinical plans. For all patients, the Auto-Planning tool produced clinically acceptable head and neck treatment plans without any manual intervention, except for the initial target and OAR delineations. The main benefit of the method is the likely improvement in the overall treatment quality since consistent, high-quality plans are generated which even can be further optimized, if necessary. This makes it possible for the dosimetrist to focus more time on difficult dose planning goals and to spend less time on the more tedious parts of the planning process. PMID- 26894365 TI - SafetyNet: Streamlining and Automating QA in radiotherapy. AB - Proper quality assurance (QA) of the radiotherapy process can be time-consuming and expensive. Many QA efforts, such as data export and import, are inefficient when done by humans. Additionally, humans can be unreliable, lose attention, and fail to complete critical steps that are required for smooth operations. In our group we have sought to break down the QA tasks into separate steps and to automate those steps that are better done by software running autonomously or at the instigation of a human. A team of medical physicists and software engineers worked together to identify opportunities to streamline and automate QA. Development efforts follow a formal cycle of writing software requirements, developing software, testing and commissioning. The clinical release process is separated into clinical evaluation testing, training, and finally clinical release. We have improved six processes related to QA and safety. Steps that were previously performed by humans have been automated or streamlined to increase first-time quality, reduce time spent by humans doing low-level tasks, and expedite QA tests. Much of the gains were had by automating data transfer, implementing computer-based checking and automation of systems with an event driven framework. These coordinated efforts by software engineers and clinical physicists have resulted in speed improvements in expediting patient-sensitive QA tests. PMID- 26894366 TI - Commissioning of a motion system to investigate dosimetric consequences due to variability of respiratory waveforms. AB - A commercially available six-dimensional (6D) motion system was assessed for accuracy and clinical use in our department. Positional accuracy and respiratory waveform reproducibility were evaluated for the motion system. The system was then used to investigate the dosimetric consequences of respiratory waveform variation when an internal target volume (ITV) approach is used for motion management. The maximum deviations are 0.3 mm and 0.22 degrees for translation and rotation accuracy, respectively, for the tested clinical ranges. The origin reproducibility is less than+/-0.1 mm. The average differences are less than 0.1 mm with a maximum standard deviation of 0.8 mm between waveforms of actual patients and replication of those waveforms by HexaMotion for three breath-hold and one free-breathing waveform. A modified gamma analysis shows greater than 98% agreement with a 0.5 mm and 100 ms threshold. The motion system was used to investigate respiratory waveform variation and showed that, as the amplitude of the treatment waveform increases above that of the simulation waveform, the periphery of the target volume receives less dose than expected. However, by using gating limits to terminate the beam outside of the simulation amplitude, the results are as expected dosimetrically. Specifically, the average dose difference in the periphery between treating with the simulation waveform and the larger amplitude waveform could be up to 12% less without gating limits, but only differed 2% or less with the gating limits in place. The general functionality of the system performs within the manufacturer's specifications and can accurately replicate patient specific waveforms. When an ITV approach is used for motion management, we found the use of gating limits that coincide with the amplitude of the patient waveform at simulation helpful to prevent the potential underdosing of the target due to changes in patient respiration. PMID- 26894367 TI - Spatially fractionated radiotherapy (GRID) using helical tomotherapy. AB - Spatially fractionated radiotherapy (GRID) was designed to treat large tumors while sparing skin, and it is usually delivered with a linear accelerator using a commercially available block or multileaf collimator (LINAC-GRID). For deep seated (skin to tumor distance (> 8 cm)) tumors, it is always a challenge to achieve adequate tumor dose coverage. A novel method to perform GRID treatment using helical tomotherapy (HT-GRID) was developed at our institution. Our approach allows treating patients by generating a patient-specific virtual GRID block (software-generated) and using IMRT technique to optimize the treatment plan. Here, we report our initial clinical experience using HT-GRID, and dosimetric comparison results between HT-GRID and LINAC-GRID. This study evaluates 10 previously treated patients who had deep-seated bulky tumors with complex geometries. Five of these patients were treated with HT-GRID and replanned with LINAC-GRID for comparison. Similarly, five other patients were treated with LINAC-GRID and replanned with HT-GRID for comparison. The prescription was set such that the maximum dose to the GTV is 20 Gy in a single fraction. Dosimetric parameters compared included: mean GTV dose (DGTV mean), GTV dose inhomogeneity (valley-to-peak dose ratio (VPR)), normal tissue doses (DNmean), and other organs-at-risk (OARs) doses. In addition, equivalent uniform doses (EUD) for both GTV and normal tissue were evaluated. In summary, HT-GRID technique is patient-specific, and allows adjustment of the GRID pattern to match different tumor sizes and shapes when they are deep-seated and cannot be adequately treated with LINAC-GRID. HT-GRID delivers a higher DGTV mean, EUD, and VPR compared to LINAC-GRID. HT-GRID delivers a higher DNmean and lower EUD for normal tissue compared to LINAC-GRID. HT-GRID plans also have more options for tumors with complex anatomical relationships between the GTV and the avoidance OARs (abutment or close proximity). PMID- 26894369 TI - AAPM Medical Physics Practice Guideline 5.a.: Commissioning and QA of Treatment Planning Dose Calculations - Megavoltage Photon and Electron Beams. PMID- 26894368 TI - Gafchromic EBT3 film dosimetry in electron beams - energy dependence and improved film read-out. AB - For megavoltage photon radiation, the fundamental dosimetry characteristics of Gafchromic EBT3 film were determined in 60Co gamma ray beam with addition of experimental and Monte Carlo (MC)-simulated energy dependence of the film for 6 MV photon beam and 6 MeV, 9 MeV, 12 MeV, and 16 MeV electron beams in water phantom. For the film read-out, two phase correction of scanner sensitivity was applied: a matrix correction for scanning area and dose-dependent correction by iterative procedure. With these corrections, the uniformity of response can be improved to be within +/- 50 pixel values (PVs). To improve the read-out accuracy, a procedure with flipped film orientations was established. With the method, scanner uniformity can be improved further and dust particles, scratches and/or dirt on scan-ner glass can be detected and eliminated. Responses from red and green channels were averaged for read-out, which decreased the effect of noise present in values from separate channels. Since the signal level with the blue channel is considerably lower than with other channels, the signal variation due to different perturbation effects increases the noise level so that the blue channel is not recommended to be used for dose determination. However, the blue channel can be used for the detection of emulsion thickness variations for film quality evaluations with unexposed films. With electron beams ranging from 6 MeV to 16 MeV and at reference measurement conditions in water, the energy dependence of the EBT3 film is uniform within 0.5%, with uncertainties close to 1.6% (k = 2). Including 6 MV photon beam and the electron beams mentioned, the energy dependence is within 1.1%. No notable differences were found between the experimental and MC-simulated responses, indicating negligible change in intrinsic energy dependence of the EBT3 film for 6 MV photon beam and 6 MeV-16 MeV electron beams. Based on the dosimetric characteristics of the EBT3 film, the read-out procedure established, the nearly uniform energy dependence found and the estimated uncertainties, the EBT3 film was concluded to be a suitable 2D dosimeter for measuring electron or mixed photon/electron dose distributions in water phantom. Uncertainties of 3.7% (k = 2) for absolute and 2.3% (k = 2) for relative dose were estimated. PMID- 26894370 TI - The Business of Scientific Publishing. PMID- 26894371 TI - Ventilatory acclimatisation is beneficial for high-intensity exercise at altitude in elite cyclists. AB - AIM: The aim of this study was to examine the relationship between ventilatory adaptation and performance during altitude training at 2700 m. METHODS: Seven elite cyclists (age: 21.2 +/- 1.1 yr, body mass: 69.9 +/- 5.6 kg, height 176.3 +/ 4.9 cm) participated in this study. A hypoxic ventilatory response (HVR) test and a submaximal exercise test were performed at sea level prior to the training camp and again after 15 d at altitude (ALT15). Ventilation (VE), end-tidal carbon dioxide partial pressure (PETCO2) and oxyhaemoglobin saturation via pulse oximetry (SpO2) were measured at rest and during submaximal cycling at 250 W. A hill climb (HC) performance test was conducted at sea level and after 14 d at altitude (ALT14) using a road of similar length (5.5-6 km) and gradient (4.8 5.3%). Power output was measured using SRM cranks. Average HC power at ALT14 was normalised to sea level power (HC%). Multiple regression was used to identify significant predictors of performance at altitude. RESULTS: At ALT15, there was a significant increase in resting VE (10.3 +/- 1.9 vs. 12.2 +/- 2.4 L.min(-1)) and HVR (0.34 +/- 0.24 vs. 0.71 +/- 0.49 L.min(-1).%(-1)), while PETCO2 (38.4 +/- 2.3 vs. 32.1 +/- 3.3 mmHg) and SpO2 (97.9 +/- 0.7 vs. 94.0 +/- 1.7%) were reduced (P < .05). Multiple regression revealed DeltaHVR and exercise VE at altitude as significant predictors of HC% (adjusted r(2) = 0.913; P = 0.003). CONCLUSIONS: Ventilatory acclimatisation occurred during a 2 wk altitude training camp in elite cyclists and a higher HVR was associated with better performance at altitude, relative to sea level. These results suggest that ventilatory acclimatisation is beneficial for cycling performance at altitude. PMID- 26894372 TI - Abstracts from the 18th International Society for Research in Human Milk and Lactation Conference. PMID- 26894373 TI - Reply. PMID- 26894374 TI - Ghost busting, taking the sheet off the ghost. PMID- 26894375 TI - Simple template fabrication of porous MnCo2O4 hollow nanocages as high performance cathode catalysts for rechargeable Li-O2 batteries. AB - Porous MnCo2O4 hollow nanocages have been fabricated via a simple template method using carbon spheres as a template. The hydrophilic surface of carbon spheres can adsorb Mn(2+) and Co(2+) ions simultaneously to form Mn,Co-adsorbed carbon spheres. The calcination of Mn,Co-adsorbed carbon spheres can result in porous hollow nanocages of MnCo2O4. The MnCo2O4 hollow nanocages are built by nanoscale MnCo2O4 crystals. Because of the unique porous hollow nanostructures, the resulting MnCo2O4/KB cathode shows an efficient electrocatalytic performance in LiTFSI/TEGDME electrolyte-based Li-O2 batteries. The MnCo2O4 hollow nanocages as the cathode catalysts can deliver better performance during the discharge/charge processes and good cycle stability compared with that of the pure KB carbon. The preliminary results manifest that porous MnCo2O4 hollow nanocages are promising high-performance cathode catalysts for Li-O2 batteries. This template technique is a simple, general, low-cost and controllable method and can be extended to prepare other transition metal oxide hollow nanostructures. PMID- 26894376 TI - Collimator optimization and collimator-detector response compensation in myocardial perfusion SPECT using the ideal observer with and without model mismatch and an anthropomorphic model observer. AB - The collimator is the primary factor that determines the spatial resolution and noise tradeoff in myocardial perfusion SPECT images. In this paper, the goal was to find the collimator that optimizes the image quality in terms of a perfusion defect detection task. Since the optimal collimator could depend on the level of approximation of the collimator-detector response (CDR) compensation modeled in reconstruction, we performed this optimization for the cases of modeling the full CDR (including geometric, septal penetration and septal scatter responses), the geometric CDR, or no model of the CDR. We evaluated the performance on the detection task using three model observers. Two observers operated on data in the projection domain: the Ideal Observer (IO) and IO with Model-Mismatch (IO-MM). The third observer was an anthropomorphic Channelized Hotelling Observer (CHO), which operated on reconstructed images. The projection-domain observers have the advantage that they are computationally less intensive. The IO has perfect knowledge of the image formation process, i.e. it has a perfect model of the CDR. The IO-MM takes into account the mismatch between the true (complete and accurate) model and an approximate model, e.g. one that might be used in reconstruction. We evaluated the utility of these projection domain observers in optimizing instrumentation parameters. We investigated a family of 8 parallel hole collimators, spanning a wide range of resolution and sensitivity tradeoffs, using a population of simulated projection (for the IO and IO-MM) and reconstructed (for the CHO) images that included background variability. We simulated anterolateral and inferior perfusion defects with variable extents and severities. The area under the ROC curve was estimated from the IO, IO-MM, and CHO test statistics and served as the figure-of-merit. The optimal collimator for the IO had a resolution of 9-11 mm FWHM at 10 cm, which is poorer resolution than typical collimators used for MPS. When the IO-MM and CHO used a geometric or no model of the CDR, the optimal collimator shifted toward higher resolution than that obtained using the IO and the CHO with full CDR modeling. With the optimal collimator, the IO-MM and CHO using geometric modeling gave similar performance to full CDR modeling. Collimators with poorer resolution were optimal when CDR modeling was used. The agreement of rankings between the IO-MM and CHO confirmed that the IO-MM is useful for optimization tasks when model mismatch is present due to its substantially reduced computational burden compared to the CHO. PMID- 26894377 TI - The prognostic significance of hematological parameters in women with uterine serous papillary carcinoma (USPC). AB - OBJECTIVES: Preoperative hematologic parameters: thrombocytosis, leukocytosis and anemia have been demonstrated to be independent poor prognostic factors in ovarian and endometrial cancers. However, little is known about their relation to uterine serous papillary carcinoma (USPC). We evaluated several preoperative hematologic parameters and their association with clinicopathologic features, disease progression and overall survival in USPC patients. STUDY DESIGN: This was a retrospective cohort study reviewing charts of all patients with a histologic pure USPC at two gynecologic oncology centers from January 2000 through July 2012. All patients had comprehensive hematologic tests prior to primary surgical treatment and were exposed to the same adjuvant treatment protocol. RESULTS: The study included 56 patients, mean age at diagnosis 69.4+/-15. Six (11%) had platelet count above 400000 10(6)/L, of them four (66%) were dead at the end of follow up (HR=1.4, p=0.48; CI 95% 0.5-4.3). The mean hemoglobin level was 12.3g/dl, fibrinogen 437.5mg/dL and lymphocytes 2013/MUL. None of these parameters was significantly associated with 5 year survival. Leukocyte and neutrophil levels were adversely associated with survival. Of 15 patients with leukocytosis >10000/MUL, 67% were dead at the end of follow up (HR=3.98, p=0.003; CI 95% 1.6-9.8). Of the 27 with neutrophils above 65%, 14 (52%) were dead at the end of follow up (HR=3.1; p=0.015; CI 95% 1.2-7.8). CONCLUSIONS: In patients with USPC, leukocytosis and neutrophilia are associated with aggressive tumor biology, and may predict a lower 5 year survival. PMID- 26894378 TI - Predictive factors for residual disease in hysterectomy specimens after conization in early-stage cervical cancer. AB - OBJECTIVE: To identify predictive factors for residual disease in hysterectomy specimens after a loop electrical excision procedure (LEEP) or cold knife conization in early-stage cervical cancer. STUDY DESIGN: A retrospective review was undertaken of the clinical records and pathology reports of 108 consecutive patients who were diagnosed with early invasive cervical cancer stage IA1 to IB1 by cold knife conization or LEEP, and underwent subsequent hysterectomy or radical hysterectomy at the Gynae-oncology Unit, Queen Elizabeth Hospital between 2000 and 2012. Residual disease was defined as the presence of cervical intra epithelial neoplasia (CIN) 2-3 or invasive carcinoma in hysterectomy specimens. Clinicopathological factors associated with residual disease were analyzed. Risk factors for the prediction of residual disease were identified by univariate and multivariate analysis. RESULTS: Residual disease was found in 32 (29.7%) patients. Stage, tumour size, depth of invasion, lymphovascular space invasion, ectocervical margin, endocervical margin, and combined ectocervical and endocervical margin were significantly associated with residual disease in hysterectomy specimens on univariate analysis. On multivariate analysis, depth of invasion (odds ratio 2.1, p=0.033) and combined margin status (odds ratio 10.8, p<=0.001) were independent risk factors for residual disease. In a subgroup analysis using depth of invasion <=5mm and a negative combined margin, none (0%) of the 52 patients who met the criteria had residual disease. CONCLUSIONS: Conization (combined ectocervical and endocervical) margin and tumour depth of invasion are independent predictors of residual disease in hysterectomy specimens. A negative conization margin and depth of invasion <=5mm are associated with low risk of residual disease in patients with early-stage cervical cancer. PMID- 26894379 TI - Giant viruses and the origin of modern eukaryotes. AB - Several authors have suggested that viruses from the NucleoCytoplasmic Large DNA Viruses group (NCLDV) have played an important role in the origin of modern eukaryotes. Notably, the viral eukaryogenesis theory posits that the nucleus originated from an ancient NCLDV-related virus. Focusing on the viral factory instead of the virion adds credit to this hypothesis, but also suggests alternative scenarios. Beside a role in the emergence of the nucleus, ancient NCLDV may have provided new genes and/or chromosomes to the proto-eukaryotic lineage. Phylogenetic analyses suggest that NCLDV informational proteins, related to those of Archaea and Eukarya, were either recruited by ancient NCLDV from proto-eukaryotes and/or transferred to proto-eukaryotes, in agreement with the antiquity of NCLDV and their possible role in eukaryogenesis. PMID- 26894381 TI - Fullerene-like Polyoxotitanium Cage with High Solution Stability. AB - We present the formation of the largest titanium-oxo cluster, [Ti42(MU3 O)60(OiPr)42(OH)12)](6-), with the first fullerene-like Ti-O shell structure. The {Ti42O60} core of this compound exemplifies the same icosahedral (Ih) symmetry as C60, the highest possible symmetry for molecules. According to the coordination environments, the Ti centers in this cluster can be arranged into a Platonic {Ti12} icosahedron and an Archimedean {Ti30} icosidodecahedron. The solution stability of this cluster was confirmed by electrospray ionization mass spectrometry. The spherical body of the {Ti42O60} core has an inside diameter of 1.05 nm and an outside diameter of 1.53 nm, which could be directly visualized by high-resolution transmission electron microscopy. Our results demonstrate that titanium oxide can also form fullerene-like shell structures. PMID- 26894380 TI - CIP2A down regulation enhances the sensitivity of pancreatic cancer cells to gemcitabine. AB - Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein which participates in inhibiting tumor apoptosis in pancreatic cancer cells. Using immunohistochemical staining, we investigated the expression of CIP2A protein in 72 cases of human pancreatic ductal adenocarcinoma (PDAC) tissue and 27 cases of adjacent normal pancreatic tissue. The positive rate of CIP2A protein expression in pancreatic cancer tissue was70.83 %, which was significantly higher than that in adjacent non- cancerous pancreatic tissue (11.11%). The expression of CIP2A was found to be correlated with TNM stage, but not correlated with age, gender, tumor location, smoking status, alcohol consumption, diabetes, high blood pressure, BMI, tumor size, lymph node metastasis or distant metastases. Kaplan- Meier survival analysis showed that patients with positive CIP2A protein expression had a lower overall survival rate than patients without CIP2A expression. COX regression analysis indicated that expression of CIP2A was an independent prognostic factor for pancreatic ductal adenocarcinoma. In addition, down-regulation of CIP2A inhibited cell proliferation and increased sensitivity to gemcitabine in pancreatic cancer cells by decreasing AKT signaling pathway. Our results indicated that down-regulation of CIP2A could be a novel therapeutic strategy for pancreatic cancer. PMID- 26894382 TI - Smoldering Multiple Myeloma: Emerging Concepts and Therapeutics. AB - Smoldering multiple myeloma (SMM) is a pre-malignant condition with an inherent risk for progression to multiple myeloma (MM). The 2014 IMWG guidelines define smoldering multiple myeloma as a monoclonal gammopathy disorder with serum monoclonal protein (IgG or IgA) >=30 g/L or urinary monoclonal protein >=500 mg per 24 h and/or clonal bone marrow plasma cells 10-60 % without any myeloma defining events or amyloidosis. The risk for progression of SMM to MM vary based on clinical, laboratory, imaging, and molecular characteristics. Observation, with periodic monitoring is the current standard of care for SMM. Over last few years, research advances in SMM have led to the delineation of newer risk factors for progression and identification of a "high-risk" group that would potentially benefit from early treatment. This review focuses on advances in the SMM risk stratification model and recent clinical trials in this patient population. PMID- 26894384 TI - Long-term operation of double chambered microbial fuel cell for bio-electro denitrification. AB - The main aim of this study is to investigate the performance of organic oxidation and denitrification of the system under long-term operation. The MFC reactor was operated in continuous mode for 180 days. Nitrate was successfully demonstrated as terminal electron acceptor, where nitrate was reduced at the cathode using electron provided by acetate oxidation at the anode. The removal efficiencies of chemical oxygen demand (COD) and nitrate were higher in the closed circuit system than in open circuit system. Both COD and nitrate reduction improved with the increase of organic loading and subsequently contributed to higher power output. The maximum nitrate removal efficiency was 88 +/- 4 % (influent of 141 +/- 14 mg/L). The internal resistant was 50 Omega, which was found to be low for a double chambered MFC. The maximum power density was 669 mW/m(3) with current density of 3487 mA/m(3). PMID- 26894383 TI - How We Identify and Manage Patients with Inadequately Controlled Polycythemia Vera. AB - Polycythemia vera (PV) is a chronic myeloproliferative neoplasm (MPN) characterized by an overactive Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway through mutations in JAK2 exons 12 or 14 (JAK2 V617F). The dominant clinical characteristics include erythrocytosis (with or without leukocytosis/thrombocytosis), thrombotic events, and symptoms. Increased risk of mortality is mainly caused by thrombotic events and progression to post polycythemia vera myelofibrosis (PPV-MF) or secondary acute myeloid leukemia (sAML). The most important prognostic factors include age and a history of thrombotic events, although recent evidence has indicated that leukocytosis and additional cytogenetic aberrations may also be of significant prognostic value. First-line therapies include aspirin and phlebotomies, which significantly reduce the incidence of thrombotic events and prolong survival. Cytoreductive treatment with hydroxyurea (approved) and conventional or pegylated interferon-alpha (effective, but not approved in many countries) is initiated for high-risk or inadequately controlled disease, e.g., uncontrolled hematocrit, leukocytosis, thrombocytosis, thrombotic events, splenomegaly, or symptoms. However, some patients may not receive initial benefit from first-line therapy or may become resistant or intolerant in due course. Although second-line treatment options are limited, clinical trials have shown the efficacy of ruxolitinib toward improving blood counts, enlarged spleen, and symptoms and potentially reducing thrombotic events. Identification of patients with uncontrolled PV is important for clinical care, as such patients have a high risk of complications, and future studies with JAK inhibitors or other agents alone or in combination are needed to test their potential to reduce rates of thrombotic events and transformation to PPV-MF or sAML. PMID- 26894385 TI - Reply to the letter "Chronic kidney disease and cognitive impairment in the very old". PMID- 26894386 TI - Erratum to: Methyl labeling and TROSY NMR spectroscopy of proteins expressed in the eukaryote Pichia pastoris. PMID- 26894387 TI - Guidelines for conducting transesophageal echocardiography (TEE) : Task force for guidelines for conducting TEE: November 15, 2015. PMID- 26894388 TI - Closer to 90-90-90. The cascade of care after 10 years of ART scale-up in rural Malawi: a population study. AB - INTRODUCTION: The antiretroviral therapy (ART) programme supported by Medecins Sans Frontieres in the rural Malawian district of Chiradzulu was one of the first in sub-Saharan Africa to scale up ART delivery in 2002. After more than a decade of continuous involvement, we conducted a population survey to evaluate the cascade of care, including population viral load, in the district. METHODS: A cross-sectional household-based survey was conducted between February and May 2013. Using a multistage cluster sampling method, we recruited all individuals aged 15 to 59 years living in 4125 randomly selected households. Each consenting individual was interviewed and tested for HIV at home. All participants who tested positive had their CD4 count and viral load measured. The LAg-Avidity assay was used to distinguish recent from long-term infections. Viral suppression was defined as a viral load below 1000 copies/mL. RESULTS: Of 8271 individuals eligible for the study, 7269 agreed to participate and were tested for HIV (94.1% inclusion for women and 80.3% for men). Overall HIV prevalence and incidence were 17.0% (95% CI 16.1 to 17.9) and 0.39 new cases per 100 person-years (95% CI 0.0 to 0.77), respectively. Coverage at the other steps along the HIV care cascade was as follows: 76.7% (95% CI 74.4 to 79.1) had been previously diagnosed, 71.2% (95% CI 68.6 to 73.6) were under care and 65.8% (95% CI 62.8 to 68.2) were receiving ART. Finally, the proportion of participants who were HIV positive with a viral load <= 1000 copies/mL reached 61.8% (95% CI 59.0 to 64.5). CONCLUSIONS: This study demonstrates that a high level of population viral suppression and low incidence can be achieved in high HIV prevalence and resource-limited settings. PMID- 26894389 TI - Enantioselective synthesis of adamantylalanine and carboranylalanine and their incorporation into the proteasome inhibitor bortezomib. AB - The incorporation of adamantylalanine and carboranylalanine at the P2 site of bortezomib is well tolerated and provided potent cell permeable proteasome inhibitors with increased off-rates compared to bortezomib. Adamantylalanine and carboranylalanine were synthesized enantioselectively by an asymmetric Strecker reaction on Ellmans tert-butyl sulfinimines. PMID- 26894391 TI - [The Patient Questionnaire "Monitoring of Exacerbation Probability (MEP)"]. AB - Exacerbations determine the disease process in COPD often decisively, whereas their detection and documentation has not been established satisfactory yet. For this purpose, a simple short Patient Questionnaire with a maximum of five positive answers was developed and evaluated. Values of 2 or more positive responses amplify the signal for an exacerbation, while with the presence of only 1 positive response a potential, but not a likely exacerbation must be considered. The MEP is well suited for a continuous documentation in computer based administration systems. PMID- 26894390 TI - Preoperative biliary drainage-related inflammation is associated with shorter survival in biliary tract cancer patients. AB - BACKGROUND: An association between inflammation and patient prognosis has been reported in various types of cancer. The aim of this study was to evaluate the influence of preoperative biliary drainage-related inflammation in patients with biliary tract cancer. METHODS: The clinical data of 97 patients who underwent surgery for extrahepatic bile duct cancer between February 2002 and September 2014 were analyzed, and the prognostic significance of tube-obstructive cholangitis after preoperative biliary drainage and pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) was evaluated. RESULTS: Eighty-four (86.6 %) of the 97 patients underwent ERCP and preoperative biliary drainage. Tube-obstructive cholangitis occurred in 25 cases and post-ERCP pancreatitis in 8 cases. Collectively, 30 patients experienced preoperative biliary drainage related inflammation consisting of tube-obstructive cholangitis and/or post-ERCP pancreatitis. Drainage-related inflammation was significant risk factor of postoperative complications (P = 0.006), and significant poor predictors of shorter progression-free survival (P = 0.003) and overall survival (OS; P = 0.006) after surgery. In multivariate analysis, drainage-related inflammation was an independent predictor of shorter OS (hazard ratio, 1.924; P = 0.037) after surgery. CONCLUSION: Preoperative biliary drainage-related inflammation was an independent prognostic factor for shorter OS in biliary tract cancer patients. PMID- 26894392 TI - Cross-Sectional Survey on Bronchoscopy in Germany--The Current Status of Clinical Practice. AB - OBJECTIVES: Bronchoscopy is an integral part of pulmonary medicine. In recent years, a series of new technologies have evolved. It is to assume that significant changes have also occurred in clinical practice. We conducted a nationwide survey to evaluate the current status of care and to compare it with earlier reports. METHODS: A standard questionnaire was sent to 1875 institutions to assess the clinical practice of bronchoscopy in Germany with respect to general issues, education, sedation/anaesthesia and technical aspects. RESULTS: The returned questionnaires cover 301,965 bronchoscopies, performed by 2158 physicians over 12 months, making it the largest survey to date. The proportion of rigid bronchoscopies has decreased and amounts to 7.3% at present. Atropine as a premedication is hardly used any more. Sedation is routinely applied in 88% of flexible bronchoscopies, for which a combination of propofol and midazolam is preferred by most institutions (41.3%), followed by propofol monotherapy (28.3%). 74.4% of institutions accept aspirin for transbronchial biopsy, 8.1% dual platelet inhibition. 62.4% of all institutions perform airway recanalisation, favouring cryotherapy and argon plasma coagulation. 9.1% of bronchoscopies are supported by endobronchial ultrasound. CONCLUSION: Compared to preceding surveys, the experience of bronchoscopists, especially regarding interventional procedures, has increased. Endobronchial ultrasound has become a standard of care, as has patient sedation with propofol. PMID- 26894393 TI - [Management and Outcome of Surgery in Patients with Severe Pulmonary Hypertension -A Single-Center Experience]. AB - BACKGROUND: Patients with pulmonary hypertension (PH) are at high risk when undergoing surgery. Up to one-third of patients suffer complications; recent studies report a mortality rate of 1 to 7%. Frequent events are deterioration of right heart function and infectious or bleeding complications. METHODS: Data of patients (age >= 18) with precapillary PH who need to undergo elective surgery between January 2006 and March 2015 were included in this retrospective analysis. All patients who were planned for surgery underwent the same procedure. First, patients were evaluated in the PH center. Thereafter, PH-relevant data were discussed with the surgeon/anesthesiologist team for risk-adapted planning of anesthesia and intervention. The present analysis comprises patient characteristics and information about surgery and post-interventional course. RESULTS: This study analyzes 31 surgical procedures carried out in PH patients (male: n = 8; PH-group I: n = 23, group III: n = 3, group IV: n = 5, mean age: 59.5 +/- 15.3 years). Patients were characterized by compromised hemodynamics and exercise capacity: pulmonary vascular resistance: 805.4 +/- 328.5 dyn*s*cm(-5), mean pulmonary arterial pressure: 46.3 +/- 9.3 mmHg, 6-minute walking distance: 350.3 +/- 123.3 m.The majority of interventions were performed under general anesthesia (n = 24). In 25 cases, the intraoperative monitoring was complemented with right heart catheterization.Eight interventions were associated with complications, three of which were serious. One patient died postoperatively owing to sepsis and right heart failure. CONCLUSION: A careful and structured planning of surgical interventions in patients with PH and the choice of surgical procedure and anesthesia adapted to the conditions of PH might help avoid complications. Further multicentric studies are needed. PMID- 26894394 TI - [Multifocal Pulmonary Neuroendocrine Tumours: Genesis, Diagnostics and Treatment]. AB - Multifocal neuroendocrine lung tumour is a rare diagnosis. Multiple lung foci of different sizes are usually apparent on chest CT scans. It is assumed that multifocal neuroendocrine lung tumours originally develop from diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH). This results in cell aggregations formed by proliferation of neuroendocrine cells that are already physiologically present in the bronchial system. If these cell proliferations break through the bronchial basement membrane, they are considered to constitute tumourlets if they measure <= 5 mm and carcinoid tumours if they are larger than 5 mm. The speed of proliferation of the cell hyperplasias appears to vary. Many of the patients are completely asymptomatic, the multifocal neuroendocrine lung tumours being diagnosed by chance. However, other patients complain of breathlessness, reduced physical capacity and cough. There may also be reduction of lung function. In these cases, chest HRCT often reveals peribronchial fibrosis or bronchiectasis in addition to the lung foci. Bronchoscopy is usually not helpful. Surgical lung biopsy is considered to be the diagnostic gold standard. Histological examination typically shows a mixture of cell hyperplasias, tumourlets and carcinoid tumours. There is no consensus on the treatment of multifocal neuroendocrine tumours. Taking the clinical situation and the chest HRCT findings as our starting point, we developed a stepwise approach that is guided by the success of the individual therapeutic procedures. The most favourable prognosis is found in affected people without clinical symptoms whose lung foci all measure less than 5 mm. In these cases the 5-year survival rate is over 90%. PMID- 26894395 TI - Examining the need profiles of patients with multiple emergency department visits for mental health reasons: a cross-sectional study. AB - OBJECTIVES: Study objectives were to: (1) provide an estimate of the prevalence of repeat emergency department (ED) use for mental health reasons among individuals enrolled in intensive case management programs; and (2) to identify socio-demographic, diagnostic, and service need characteristics associated with repeat ED visits among this service population. METHODS: The study utilized administrative health data from community mental health organizations in Toronto, Canada on a sample of 2274 individuals enrolled in intensive case management programs. Patients with 2+ ED visits for mental health reasons within the prior 6 months were compared with individuals who had no ED visits or one visit on the basis of demographic, diagnostic and service need characteristics. RESULTS: Approximately 6 % of intensive case management clients had two or more ED visits over a 6-month period. Membership in the repeat ED user group was associated with younger age (OR 0.98), a mood disorder (OR 1.58), being in service less than 1 year (OR 1.94) and unmet needs related to psychotic symptoms (OR 2.19), substance use (OR 2.27), and safety to self/others (OR 3.42). CONCLUSIONS: The repeat ED user group within case management may have distinct need profiles that require different treatment responses. Moreover, clinical needs rather than psychosocial needs have the greatest relationship with repeat psychiatric ED utilization. These unmet needs suggest areas for future interventions aimed at reducing the use of ED services for mental health reasons and improving care for patients who repeatedly present at the ED. PMID- 26894398 TI - A Fluorescent and Switchable Rotaxane Dual Organocatalyst. AB - Rotaxane organocatalysis presents a new direction toward controlled one-pot catalytic reactions. By combining molecular switches and catalysts, fluorescence and pH-responsive switching along with the exclusive selectivity of dual catalytic reactions are demonstrated. A newly designed [2]rotaxane catalyst containing an anthracene group was used to visualize the catalytic reaction process upon switching the macrocycle. PMID- 26894396 TI - Microglial Polarization and Inflammatory Mediators After Intracerebral Hemorrhage. AB - Intracerebral hemorrhage (ICH) is a subtype of stroke with high mortality and morbidity. When a diseased artery within the brain bursts, expansion and absorption of the resulting hematoma trigger a series of reactions that cause primary and secondary brain injury. Microglia are extremely important for removing the hematoma and clearing debris, but they are also a source of ongoing inflammation. This article discusses the role of microglial activation/polarization and related inflammatory mediators, such as Toll-like receptor 4, matrix metalloproteinases, high-mobility group protein box-1, nuclear factor erythroid 2-related factor 2, heme oxygenase, and iron, in secondary injury after ICH and highlights the potential targets for ICH treatment. PMID- 26894399 TI - Minor Anesthesia-Related Events During Radiofrequency Ablation for Barrett's Esophagus Are Associated with an Increased Number of Treatment Sessions. AB - BACKGROUND: There is limited data regarding the prevalence and clinical impact of sedation-related adverse events (SRAEs) during radiofrequency ablation (RFA) for dysplastic Barrett's esophagus (BE). AIM: Our primary aim was to measure SRAE during RFA. Secondary aims were to identify risk factors for adverse events, and to determine whether SRAEs impacted the number of RFA treatments to achieve complete eradication of dysplasia (CE-D). METHODS: We conducted a retrospective analysis of 120 consecutive patients undergoing initial RFA for dysplastic BE between 2008 and 2014. The main outcome measures were SRAEs and the number of RFA sessions required to achieve CE-D. RESULTS: Of 120 initial RFA procedures, 83 % were performed with MAC and 17 % with GET. SRAEs occurred in 32 %, including 25 % of MAC patients (25/100) and 65 % (12/20) GET patients. The most frequent SRAE was hypotension (23 %, n = 27/120), followed by hypoxia (n = 9/120), arrhythmia (n = 4/120), and one unplanned intubation. There were no premature procedure terminations. After adjusting for length of BE mucosa and ASA score, the occurrence of a SRAE was associated with requiring more (>4) RFA sessions to achieve CE-D, OR 3.45 (95 % CI 1.49-7.99). Mean RFA sessions required to achieve CE-D was 5 +/- 1 in patients with SRAE, compared to 3 +/- 0.7 in patients without SRAE during the first treatment session (p < 0.001). CONCLUSIONS: SRAE during RFA for dysplastic BE occurs at a rate typical of other advanced endoscopic procedures. Patients who experience minor events related to anesthesia during the first RFA are likely to require more RFA treatment sessions to achieve CE-D. PMID- 26894400 TI - Psoriasiform Skin Lesions Are Caused by Both Infliximab and Adalimumab in a Patient with Crohn's Disease. PMID- 26894397 TI - The Emerging Role of Epigenetics in Cerebral Ischemia. AB - Despite great progresses in the treatment and prevention of ischemic stroke, it is still among the leading causes of death and serious long-term disability all over the world, indicating that innovative neural regenerative and neuroprotective agents are urgently needed for the development of therapeutic approaches with greater efficacy for ischemic stroke. More and more evidence suggests that a spectrum of epigenetic processes play an important role in the pathophysiology of cerebral ischemia. In the present review, we first discuss recent developments in epigenetic mechanisms, especially their roles in the pathophysiology of cerebral ischemia. Specifically, we focus on DNA methylation, histone deacetylase, histone methylation, and microRNAs (miRNAs) in the regulation of vascular and neuronal regeneration after cerebral ischemia. Additionally, we highlight epigenetic strategies for ischemic stroke treatments, including the inhibition of histone deacetylase enzyme and DNA methyltransferase activities, and miRNAs. These therapeutic strategies are far from clinic use, but preliminary data indicate that neuroprotective agents targeting these pathways can modulate neural cell regeneration and promote brain repair and functional recovery after cerebral ischemia. A better understanding of how epigenetics influences the process and progress of cerebral ischemia will pave the way for discovering more sensitive and specific biomarkers and new targets and therapeutics for ischemic stroke. PMID- 26894401 TI - A Risk Prediction Model for Sporadic CRC Based on Routine Lab Results. AB - BACKGROUND: Current risk scores for colorectal cancer (CRC) are based on demographic and behavioral factors and have limited predictive values. AIM: To develop a novel risk prediction model for sporadic CRC using clinical and laboratory data in electronic medical records. METHODS: We conducted a nested case-control study in a UK primary care database. Cases included those with a diagnostic code of CRC, aged 50-85. Each case was matched with four controls using incidence density sampling. CRC predictors were examined using univariate conditional logistic regression. Variables with p value <0.25 in the univariate analysis were further evaluated in multivariate models using backward elimination. Discrimination was assessed using receiver operating curve. Calibration was evaluated using the McFadden's R2. Net reclassification index (NRI) associated with incorporation of laboratory results was calculated. Results were internally validated. RESULTS: A model similar to existing CRC prediction models which included age, sex, height, obesity, ever smoking, alcohol dependence, and previous screening colonoscopy had an AUC of 0.58 (0.57-0.59) with poor goodness of fit. A laboratory-based model including hematocrit, MCV, lymphocytes, and neutrophil-lymphocyte ratio (NLR) had an AUC of 0.76 (0.76-0.77) and a McFadden's R2 of 0.21 with a NRI of 47.6 %. A combined model including sex, hemoglobin, MCV, white blood cells, platelets, NLR, and oral hypoglycemic use had an AUC of 0.80 (0.79-0.81) with a McFadden's R2 of 0.27 and a NRI of 60.7 %. Similar results were shown in an internal validation set. CONCLUSION: A laboratory-based risk model had good predictive power for sporadic CRC risk. PMID- 26894402 TI - High-throughput screening methods for nitrilases. AB - Nitrilases have been widely acknowledged as important alternatives to chemical catalysts, as they have been proved to transform an immense variety of nitriles under mild conditions and often in a stereoselective or regioselective manner. In the discovery of new nitrilases to establish viable industrial processes, screening plays an important role in identifying which subset of candidates contains a nitrilase of interest from a collection of organisms, clone banks, or enzyme libraries. However, the traditional methods for evaluating the nitrilases are a time-consuming, laborious, and costly process and have been regarded as a bottleneck in developing these nitrilases as industrial biocatalysts. In the past few years, a number of high-throughput screening methods have been developed for rapid evaluation and identification of nitrilases. Here, we review the various methodologies developed for high-throughput screening of nitrilases and focus on their advantages and limitations. PMID- 26894403 TI - The effects of fulvic acid on microbial denitrification: promotion of NADH generation, electron transfer, and consumption. AB - The heterotrophic denitrification requires the participation of electrons which are derived from direct electron donor (usually nicotinamide adenine dinucleotide (NADH)), and the electrons are transferred via electron transport system in denitrifiers and then consumed by denitrifying enzymes. Despite the reported electron transfer ability of humic substances (HS), the influences of fulvic acid (FA), an ubiquitous major component of HS, on promoting NADH generation, electron transfer, and consumption in denitrification process have never been reported. The presence of FA, compared with the control, was found not only significantly improved the total nitrogen (TN) removal efficiency (99.9 % versus 74.8 %) but remarkably reduced the nitrite accumulation (0.2 against 43.8 mg/L) and N2O emission (0.003 against 0.240 mg nitrogen/mg TN removed). The mechanisms study showed that FA increased the metabolism of carbon source via glycolysis and tricarboxylic acid (TCA) cycle pathways to produce more available NADH. FA also facilitated the electron transfer activities from NADH to denitrifying enzymes via complex I and complex III in electron transport system, which improved the reduction of nitrate and accelerated the transformations of nitrite and N2O, and lower nitrite and N2O accumulations were therefore observed. In addition, the consumption of electrons in denitrification was enhanced due to FA stimulating the synthesis and the catalytic activity of key denitrifying enzymes, especially nitrite reductase and N2O reductase. It will provide an important new insight into the potential effect of FA on microbial denitrification metabolism process and even nitrogen cycle in nature niches. PMID- 26894404 TI - A small molecule norspermidine in combination with silver ion enhances dispersal and disinfection of multi-species wastewater biofilms. AB - Detrimental biofilms have become a great concern in many areas due to their strong resistance and insensitivity to traditional antimicrobial agents. Norspermidine is a potent small molecule for biofilm dispersal. In this study, silver ion, a conventional inorganic biocide, was combined with norspermidine and used for control and removal of multi-species biofilms formed by a mixed culture from wastewater treatment systems. Results showed that silver ion (0.01-1 mg/L) treatment alone failed to remove the existing wastewater biofilms. Norspermidine at the concentrations of 500-1000 MUM was capable to disrupt and disperse the existing biofilms with a biofilm reduction of 21-34 % after 24-h exposure. The combined treatment with norspermidine (500 MUM) and silver ion (0.01 mg/L) increased biofilm reduction to 48 % (24-h exposure). The combined treatment also enhanced biofilm disinfection ratio (82 %, 2-h exposure) by 2.0- and 2.6-folds compared to norspermidine (27 %) or silver ion (23 %) treatment alone, respectively. Confocal laser scanning microscopic (CLSM) observations found that norspermidine could disrupt biofilm matrix and promote biofilm dispersal via breaking down exopolysaccharides. The combined treatment increased the reduction in biofilm cell density and viability, possibly due to the damage of biofilm matrix, enhanced silver ion diffusion in biofilms, and increased biofilm sensitivity. These findings indicate that the combination of a small molecule norspermidine with a traditional biocide silver ion presents a novel strategy to remove and kill biofilms, which have a potential application in addressing wastewater biofilm-related issues. PMID- 26894406 TI - Binding of Crumbs to the Par-6 CRIB-PDZ Module Is Regulated by Cdc42. AB - Par-6 is a scaffold protein that organizes other proteins into a complex required to initiate and maintain cell polarity. Cdc42-GTP binds the CRIB module of Par-6 and alters the binding affinity of the adjoining PDZ domain. Allosteric regulation of the Par-6 PDZ domain was first demonstrated using a peptide identified in a screen of typical carboxyl-terminal ligands. Crumbs, a membrane protein that localizes a conserved polarity complex, was subsequently identified as a functional partner for Par-6 that likely interacts with the PDZ domain. Here we show by nuclear magnetic resonance that Par-6 binds a Crumbs carboxyl-terminal peptide and report the crystal structure of the PDZ-peptide complex. The Crumbs peptide binds Par-6 more tightly than the previously studied carboxyl peptide ligand and interacts with the CRIB-PDZ module in a Cdc42-dependent manner. The Crumbs:Par-6 crystal structure reveals specific PDZ-peptide contacts that contribute to its higher affinity and Cdc42-enhanced binding. Comparisons with existing structures suggest that multiple C-terminal Par-6 ligands respond to a common conformational switch that transmits the allosteric effects of GTPase binding. PMID- 26894407 TI - Protein-Coupled Fluorescent Probe To Visualize Potassium Ion Transition on Cellular Membranes. AB - K(+) is the most abundant metal ion in cells, and changes of [K(+)] around cell membranes play important roles in physiological events. However, there is no practical method to selectively visualize [K(+)] at the surface of cells. To address this issue, we have developed a protein-coupled fluorescent probe for K(+), TLSHalo. TLSHalo is responsive to [K(+)] in the physiological range, with good selectivity over Na(+) and retains its K(+)-sensing properties after covalent conjugation with HaloTag protein. By using cells expressing HaloTag on the plasma membrane, we successfully directed TLSHalo specifically to the outer surface of target cells. This enabled us to visualize localized extracellular [K(+)] change with TLSHalo under a fluorescence microscope in real time. To confirm the experimental value of this system, we used TLSHalo to monitor extracellular [K(+)] change induced by K(+) ionophores or by activation of a native Ca(2+)-dependent K(+) channel (BK channel). Further, we show that K(+) efflux via BK channel induced by electrical stimulation at the bottom surface of the cells can be visualized with TLSHalo by means of total internal reflection fluorescence microscope (TIRFM) imaging. Our methodology should be useful to analyze physiological K(+) dynamics with high spatiotemporal resolution. PMID- 26894408 TI - Establishing the Family of Diruthenium Water Oxidation Catalysts Based on the Bis(bipyridyl)pyrazolate Ligand System. AB - A bis(bipyridyl)pyrazolate ((Me)bbp(-)) has recently been introduced as a rugged dinucleating, bis(tridentate) ligand for the formation of efficient diruthenium water oxidation catalysts (J. Am. Chem. Soc. 2014, 136, 24-27). Now, detailed protocols for the synthesis of a whole family of such dinuclear ruthenium complexes [{Ru(pyR(2))2}2(MU-(R1)bbp)(X,Y)](2+) based on the bis(bipyridyl)pyrazolate scaffold are reported. The isolation of a synthetic key intermediate allowed the straightforward introduction of different pyridines as axial ligands. Thereby, a set of complexes with different substituents at the pyrazolate backbone (R(1) = Br, H, Me), different pyridines as axial ligand (R(2) = H, NMe2, SO3), and different (non)bridging units in the in,in-position (X,Y = Cl, H2O, OAc) has been prepared and thoroughly characterized. Complexes of the type [{Ru(pyR(2))2}2(MU-(R1)bbp)(MU-OAc)](2+), with an exogenous acetato bridge, have been used as catalyst precursors in catalytic water oxidation experiments with a sacrificial oxidant. The effect of substitution on the pyrazole core of the (R1)bbp(-) ligand as well as on the pyridine ligands on both electrochemistry and catalytic activity has been systematically investigated. The catalyst stability, reflected by the turnover number, is crucially determined by the substituent at the pyrazolate ligand (R(1) = Me > H > Br). In contrast, the axial pyridine ligands modulate the rate of the catalytic process, expressed by the initial turnover frequency (R(2) = H > NMe2H(+)). PMID- 26894409 TI - Synthesis of Benzo[c]thiophenes by Rhodium(III)-Catalyzed Dehydrogenative Annulation. AB - The dehydrogenative annulation of thiophen-2-carboxamides with 2 equiv of alkynes proceeds efficiently in the presence of a rhodium catalyst and a copper oxidant to furnish multiply substituted benzo[c]thiophenes. Some of the synthesized benzo[c]thiophenes exhibited strong solid-state fluorescence. PMID- 26894405 TI - Pluripotent stem cells and livestock genetic engineering. AB - The unlimited proliferative ability and capacity to contribute to germline chimeras make pluripotent embryonic stem cells (ESCs) perfect candidates for complex genetic engineering. The utility of ESCs is best exemplified by the numerous genetic models that have been developed in mice, for which such cells are readily available. However, the traditional systems for mouse genetic engineering may not be practical for livestock species, as it requires several generations of mating and selection in order to establish homozygous founders. Nevertheless, the self-renewal and pluripotent characteristics of ESCs could provide advantages for livestock genetic engineering such as ease of genetic manipulation and improved efficiency of cloning by nuclear transplantation. These advantages have resulted in many attempts to isolate livestock ESCs, yet it has been generally concluded that the culture conditions tested so far are not supportive of livestock ESCs self-renewal and proliferation. In contrast, there are numerous reports of derivation of livestock induced pluripotent stem cells (iPSCs), with demonstrated capacity for long term proliferation and in vivo pluripotency, as indicated by teratoma formation assay. However, to what extent these iPSCs represent fully reprogrammed PSCs remains controversial, as most livestock iPSCs depend on continuous expression of reprogramming factors. Moreover, germline chimerism has not been robustly demonstrated, with only one successful report with very low efficiency. Therefore, even 34 years after derivation of mouse ESCs and their extensive use in the generation of genetic models, the livestock genetic engineering field can stand to gain enormously from continued investigations into the derivation and application of ESCs and iPSCs. PMID- 26894410 TI - Rational Design of Graphene-Reinforced MnO Nanowires with Enhanced Electrochemical Performance for Li-Ion Batteries. AB - Recently, transition metal oxides (TMOs) mixed with carbon materials have attracted attention as lithium-ion battery (LIB) anode materials. However, the aggregation issue in TMOs hinders the development of an ideal encapsulation structure with carbon materials. In this paper, we report graphene reinforced MnO nanowires with enhanced electrochemical performance as an anode in LIB. The graphene nanosheets (GNs)/MnO feature was confirmed by transmission electron microscopy, X-ray diffraction, Raman scattering, and X-ray photoelectron spectroscopy. The GNs/MnO nanowires delivered a highly stable discharge capacity of ~815 mAh g(-1) at a current density of 100 mA g(-1) after 200 cycles, which is 1.5 times higher than that of pure MnO nanowires. This GNs/MnO structure with a specific capacity of ~995 mAh g(-1) at a current density of 50 mA g(-1) also exhibited excellent Li storage properties. The superior cycling and high rate capability were attributed to the intimate incorporation between the MnO and GNs. The structure of the GNs/MnO nanowires effectively accommodated the volume change of the MnO nanowires and prevented structure collapse during cycling. PMID- 26894411 TI - Parent education discharge instruction program for care of children at home after cardiac surgery in Southern India. AB - Introduction In many developing countries, children with CHD are now receiving surgical repair or palliation for their complex medical condition. Consequently, parents require more in-depth discharge education programmes to enable them to recognise complications and manage their children's care after hospital discharge. This investigation evaluated the effectiveness of a structured nurse led parent discharge teaching programme on nurse, parent, and child outcomes in India. Materials and methods A quasi-experimental investigation compared nurse and parent home care knowledge before and at two time points after the parent education discharge instruction program's implementation. Child surgical-site infections and hospital costs were compared for 6 months before and after the discharge programme's implementation. RESULTS: Both nurses (n=63) and parents (n=68) participated in this study. Records of 195 children who had undergone cardiac surgery were reviewed. Nurses had a high-level baseline home care knowledge that increased immediately after the discharge programme's implementation (T1=24.4+/-2.89; T2=27.4+/-1.55; p0.05) after the programme's implementation. CONCLUSION: Nurse, parent, and child outcomes were improved after implementation of the structured nurse-led parent discharge programme for parents in India. Structured nurse-led parent discharge programmes may help prepare parents to provide better home care for their children after cardiac surgery. Further investigation of causality and influencing factors is warranted. PMID- 26894413 TI - Impact of palbociclib plus letrozole on pain severity and pain interference with daily activities in patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer as first-line treatment. AB - Background Palbociclib is a recently approved drug for use in combination with letrozole as initial endocrine-based therapy for the treatment of postmenopausal women with advanced estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer. This report assesses the impact of palbociclib in combination with letrozole versus letrozole alone on patient reported outcomes of pain. Methods Palbociclib was evaluated in an open-label, randomized, phase II study (PALOMA-1/TRIO-18) among postmenopausal women with advanced ER+/HER2- breast cancer who had not received prior systemic treatment for their advanced disease. Patients received continuous oral letrozole 2.5 mg daily alone or the same letrozole dose and schedule plus oral palbociclib 125 mg, given once daily for 3 weeks followed by 1 week off over repeated 28-day cycles. The primary study endpoint was investigator-assessed progression-free survival in the intent-to-treat population, and these results have recently been published (Finn et al., Lancet Oncol 2015;16:25-35). One of the key secondary endpoints was the evaluation of pain, as measured using the Brief Pain Inventory (BPI) patient reported outcome tool. The BPI was administered at baseline and on day 1 of every cycle thereafter until disease progression and/or treatment discontinuation. Clinical trial registration This study is registered with ClinicalTrials.gov (NCT00721409). Results There were no statistically significant differences in Pain Severity or Pain Interference scores of the BPI between the two treatment groups for the overall population or among those with any bone disease at baseline. A limitation of the study is that results were not adjusted for the concomitant use of opioids or other medications used to control pain. Conclusions The addition of palbociclib to letrozole was associated with increased efficacy without negatively impacting pain severity or pain interference with daily activities. PMID- 26894414 TI - Correction to Enhanced Transport into and out of Dead-End Pores. PMID- 26894415 TI - Detection of eustachian tube openings by tubomanometry in adult otitis media with effusion. AB - Otitis media with effusion (OME) is a common disease and eustachian tube (ET) dysfunction is widely known to be related to the incidence of OME; however, objective evaluation tools for ET function are lacking. To evaluate ET openings by tubomanometry (TMM) in adult patients with otitis media with effusion (OME), the ET patency of 123 ears, including 63 ears of OME patients and 60 control ears, were tested using TMM and tympanometry. ET patency was evaluated by the R value and ET score, and was compared to the tympanogram results. The eustachian tube dysfunction questionnaire (ETDQ-7) was used to assess the severity of the symptoms in OME patients. The results showed that the rates of restricted opening or blocked ET under pressures of 30, 40, and 50 mbar by TMM testing were 10, 5, and 0 %, respectively (control group) and 76.19, 66.7, and 57.97 %, respectively (OME group) (p < 0.05 for all pressure groups). However, the rates were 77.42, 71.97, and 61.29 % in the type B tympanogram group, and 75, 62.5, and 46.87 % in the type C tympanogram group; no significant difference was found at each testing pressure (p = 0.821, 0.246, and 0.516; respectively) between these tympanogram groups. The mean ETDQ-7 score in OME patients was 16.40 +/- 10.72, which was significantly negatively correlated with the ET score at 30 and 40 mbar (30 mbar: correlation coefficient -0.29, p = 0.025; 40 mbar: correlation coefficient -0.28; p = 0.030), but not at 50 mbar (correlation coefficient -0.013, p = 0.924). These findings showed that ET blockage or delayed opening were found in most adult patients with OME when evaluated by this innovative and semi objective TMM, testing pressures should be considered when assessing the results of TMM in OME patients. PMID- 26894412 TI - Functioning of drug-metabolizing microsomal cytochrome P450s: In silico probing of proteins suggests that the distal heme 'active site' pocket plays a relatively 'passive role' in some enzyme-substrate interactions. AB - PURPOSE: The currently held mechanistic understanding of microsomal cytochrome P450s (CYPs) seeks that diverse drug molecules bind within the deep-seated distal heme pocket and subsequently react at the heme centre. To explain a bevy of experimental observations and meta-analyses, we indulge a hypothesis that involves a "diffusible radical mediated" mechanism. This new hypothesis posits that many substrates could also bind at alternate loci on/within the enzyme and be reacted without the pertinent moiety accessing a bonding proximity to the purported catalytic Fe-O enzyme intermediate. METHODS: Through blind and heme distal pocket centered dockings of various substrates and non-substrates (drug molecules of diverse sizes, classes, topographies etc.) of microsomal CYPs, we explored the possibility of access of substrates via the distal channels, its binding energies, docking orientations, distance of reactive moieties (or molecule per se) to/from the heme centre, etc. We investigated specific cases like- (a) large drug molecules as substrates, (b) classical marker drug substrates, (c) class of drugs as substrates (Sartans, Statins etc.), (d) substrate preferences between related and unrelated CYPs, (e) man-made site directed mutants' and naturally occurring mutants' reactivity and metabolic disposition, (f) drug-drug interactions, (g) overall affinities of drug substrate versus oxidized product, (h) meta-analysis of in silico versus experimental binding constants and reaction/residence times etc. RESULTS: It was found that heme-centered dockings of the substrate/modulator drug molecules with the available CYP crystal structures gave poor docking geometries and distances from Fe-heme centre. In conjunction with several other arguments, the findings discount the relevance of erstwhile hypothesis in many CYP systems. Consequently, the newly proposed hypothesis is deemed a viable alternate, as it satisfies Occam's razor. CONCLUSIONS: The new proposal affords expanded scope for explaining the mechanism, kinetics and overall phenomenology of CYP mediated drug metabolism. It is now understood that the heme-iron and the hydrophobic distal pocket of CYPs serve primarily to stabilize the reactive intermediate (diffusible radical) and the surface or crypts of the apoprotein bind to the xenobiotic substrate (and in some cases, the heme distal pocket could also serve the latter function). Thus, CYPs enhance reaction rates and selectivity/specificity via a hitherto unrecognized modality. PMID- 26894416 TI - Bone-anchored hearing aids in conductive and mixed hearing losses: why do patients reject them? AB - This study aimed to report the bone-anchored hearing aid uptake rate and the reasons for their rejection by patients with conductive and mixed hearing losses. A retrospective review was performed of 113 consecutive patients with unilateral or bilateral conductive or mixed hearing loss referred to the Greater Manchester bone-anchored hearing aid (BAHA) programme between September 2008 and August 2011. 98 (86.7 %) patients were deemed audiologically suitable for BAHA implantation. Of these, 38 (38.8 %) had BAHA implanted; 60 (61.2 %) patients declined. Of those who declined, 27 (45 %) cited anxiety over surgery, 18 (30 %) cited cosmetic reasons, 16 (26.7 %) perceived limited benefit from the device and six (10 %) preferred conventional hearing aids. Our study highlights a 38.8 % BAHA uptake rate in audiologically suitable patients. The main reasons cited for rejection of BAHA were anxiety over surgery and cosmetic concerns. It is important that clinicians address these early during consultation with prospective BAHA recipients and avoid rushing to implant these patients with a bone-anchored hearing aid. PMID- 26894417 TI - The laryngeal disease of the German Emperor Friedrich III: treatment failure or fateful course. AB - BACKGROUND: Since the death of the Emperor Friedrich III in June 1888, there are still controversial discussions whether the Crown Prince could have been healed from his laryngeal cancer by a thyrotomy planned by his German physicians for May 21, 1887. METHODS: In order to find an answer to this historical question, the Emperor's biographies, the literature on laryngology published in the late nineteenth and early twentieth century, German manuals on laryngology and ENT, the BMJ and Lancet were thoroughly studied where in particular not only Mackenzie but also Virchow had published several articles on the disease of Friedrich III. RESULTS: Prof. Gerhardt had decided not to perform biopsies of the tumor. Furthermore, he did not perform iodine potassium treatment ex juvantibus as it was common practice at that time in order to confirm the diagnosis of carcinoma by excluding syphilitic gumma. So Mackenzie was perfectly right when insisting on performing excisional biopsy before surgery. It is tragedy that Virchow by making the diagnosis of pachydermia laryngis provided the justification for canceling the surgical intervention that had already been decided. It was also mistake that Prof. Gerhardt did not accompany the Crown Prince during his stay in England in summer 1887. The authority of the delegated medical officer Dr. Landgraf did not suffice to persuade Mackenzie to discuss again the matter of performing surgery together with Gerhardt and von Bergmann. The drawings made by Dr. Landgraf show an impressive tumor growth. The refusal of new consultations with Gerhardt and von Bergmann by Mackenzie can only be explained by the fact that Mackenzie was generally against such a surgical intervention. Regarding the question of the chances of such a surgery it can be said that thyrotomy and laryngectomy had been refused by the majority of laryngologists since the Congress of London in 1881 and the publication of P. v. Bruns in 1878. In Berlin, however, the improvement of surgical and anesthetic techniques by E. Hahn led to a positive opinion. F. Semon, who had strictly refused thyrotomy until 1886, supported the indication of thyrotomy of the Crown Prince since Hahn had successfully operated one of his patients in London. So the chance of healing a limited carcinoma of the vocal folds by thyrotomy was given. However, it may be questioned if partial resection had the desired outcome. The limited mobility of the left vocal fold that had been diagnosed already in May 1887 indicates that probably laryngectomy would have been necessary. The prognosis of this procedure, however, was extremely poor at that time. It is irony of history that T. Gluck who performed the separation of the airways from the digestive pathways in an animal model already in 1880 under von Langenbeck could not further develop his technique under von Bergmann. CONCLUSIONS: The Crown Prince acquired his disease at a time when the acceptance of surgical treatment of laryngeal carcinomas had reached its lowest point. Ten years later, the technique of thyrotomy was successfully established by Hahn, Butlin, and Semon so that Morell Mackenzie would probably have agreed to the intervention. Ten years later, due to Gluck and Sorensen, even the technique of laryngectomy had reached the performance that is still valid today so that the Emperor could have been treated successfully even with an advanced laryngeal carcinoma. PMID- 26894418 TI - Diagnostic and prognostic value of procalcitonin levels in patients with Bell's palsy. AB - Inflammation is thought to play an important role in the pathogenesis of Bell's palsy (BP). Procalcitonin (PCT) is currently among the most frequently used proinflammatory biomarkers in clinical practice. In this study, we assessed the serum PCT levels for predicting the severity and prognosis of BP. In total, 32 patients with House-Brackmann (HB) grade II and III BP (low-grade group), 22 patients with HB grade IV and V (high-grade group) and 35 healthy individuals (control group) were included in this prospective study. PCT levels were compared among these three groups at the time of diagnosis. All patients received standard prednisolone and acyclovir treatment. The correlation between PCT levels and recovery was analyzed 3 months after treatment. The PCT levels for control, low grade and high-grade BP groups were 0.01 +/- 0.001, 0.35 +/- 0.05, and 0.98 +/- 0.41 ng/mL, respectively. The PCT level in low-grade group was significantly higher than that in control group (p < 0.001), and the PCT level in high-grade BP group was significantly higher than that in low-grade group (p = 0.01, p < 0.05). The complete recovery rate was 93.7 % in low-grade and 54.5 % in high-grade BP group (p = 0.015, p < 0.05). There was a strong negative correlation between PCT levels and recovery rates (r = -0.896, p < 0.001). PCT levels were significantly associated with the severity of BP and higher PCT levels were related with poor clinical outcome in terms of recovery. These results support the diagnostic and prognostic significance of PCT in patients with early BP. PMID- 26894419 TI - The association between phthalate exposure and atopic dermatitis with a discussion of phthalate induced secretion of interleukin-1beta and thymic stromal lymphopoietin. AB - Phthalate diesters are widely used as emollients in plastic and cosmetics as well as in food packaging and perfumes, potentially leading to prolonged and repeated dermal, oral and airborne exposure. We here review published articles that have evaluated the putative role of phthalate diesters in the pathogenesis of atopic dermatitis and discuss possible pathogenic pathways. A literature search resulted in 563 articles in Embase and 263 articles in Pubmed. After identification of relevant articles based on screening of titles, abstracts and reference lists, a total of 39 articles were selected and included. While no clear association has been shown between systemic phthalate levels and atopic dermatitis in human studies, animal data suggests that phthalates may worsen dermatitis and in vitro data suggests that interleukin-4 could be upregulated. Moreover, both loss-of function mutations in the filaggrin gene and atopic dermatitis have been associated with elevated systemic phthalate levels. There is a need for prospective studies to clarify the possible pathogenic role of phthalate diesters in atopic dermatitis and the associated health risk, especially with the general trend towards barrier restoration with emollients in infants at risk of developing atopic dermatitis. In summary, we conclude that the results from published studies are controversial and inconclusive. PMID- 26894420 TI - Cognitive Hypnotherapy as a Transdiagnostic Protocol for Emotional Disorders. AB - This article describes cognitive hypnotherapy (CH), an integrative treatment that provides an evidence-based framework for synthesizing clinical practice and research. CH combines hypnotherapy with cognitive-behavior therapy in the management of emotional disorders. This blended version of clinical practice meets criteria for an assimilative model of integrative psychotherapy, which incorporates both theory and empirical findings. Issues related to (a) additive effect of hypnosis in treatment, (b) transdiagnostic consideration, and PMID- 26894421 TI - Role of Beliefs About Hypnotic States as a Moderator Variable: A Reexamination of the Relationship Between Reactance and Hypnotizability. AB - The hypothesis that beliefs about hypnosis determine the amount of psychological reactance aroused was tested. Participants were administered a measure of trait reactance to therapist directives (Therapeutic Reactance Scale; TRS), the Beliefs about Hypnotic State Questionnaire (BHSQ-R), and behavioral and subjective scales concerning hypnotic response. Hierarchical multiple regressions revealed significant interactions between BHSQ-R subscales and TRS. The findings suggest that the arousal of psychological reactance to hypnosis is determined by individuals' trait reactance levels acting together with their interpretations of the hypnotic situation. The role of beliefs about hypnotic states as a moderator of the relationship between personality and hypnotizability was discussed. PMID- 26894422 TI - Effectiveness of Self-Hypnosis on the Relief of Experimental Dental Pain: A Randomized Trial. AB - This randomized, controlled clinical trial evaluates the effectiveness of self hypnosis on pain perception. Pain thresholds were measured, and a targeted, standardized pain stimulus was created by electrical stimulation of the dental pulp of an upper anterior tooth. Pain stimulus was rated by a visual analogue scale (VAS). The pain threshold under self-hypnosis was higher (57.1 +/- 17.1) than without hypnotic intervention (39.5 +/- 11.8) (p < .001). Pain was rated lower on the VAS with self-hypnosis (4.0 +/- 3.8) than in the basal condition without self-hypnosis (7.1 +/- 2.7) (p < .001). Self-hypnosis can be used in clinical practice as an adjunct to the gold standard of local anesthesia for pain management, as well as an alternative in individual cases. PMID- 26894423 TI - Hypnosis Attenuates Executive Cost of Prospective Memory. AB - Prospective memory is the ability to formulate and carry out actions at the appropriate time or in the appropriate context. This study aimed to identify the effect of hypnosis on prospective memory performance and to analyze the involvement of executive control processes in intention realization in a hypnotically altered state of consciousness. In 1 experiment, manipulating hypnotic instruction in a within-subject fashion, the authors explored the event based prospective memory performance of 23 volunteers in 3 conditions: baseline, expectation, and execution. The primary result was that executing prospective memory responses, at the same accuracy rate, produced a significantly lower cost of ongoing responses in terms of response latency in the hypnotic state than in wake condition. PMID- 26894424 TI - Hypnotic Relaxation Therapy and Sexual Function in PostmenopausalWomen: Results of a Randomized Clinical Trial. AB - Sexual dysfunction is a common problem for postmenopausal women. This study, as part of a larger randomized controlled trial, examined the effect of hypnotic relaxation therapy on sexual dysfunction, a secondary study outcome, in postmenopausal women. Sexual function was assessed using the Sexual Activity Questionnaire (SAQ). Significant improvement in sexual pleasure and discomfort were reported following 5 weekly sessions of hypnotic relaxation therapy, compared with those receiving an attention control. Total SAQ scores showed significant improvement in the hypnotic relaxation therapy treatment group while holding baseline SAQ scores constant. Improvements showed a slight increase at the Week 12 follow-up. The results of this analysis provide initial support for the use of hypnotic relaxation therapy to improve sexual function in postmenopausal women. PMID- 26894425 TI - Think Yourself Thin: Concern for Appropriateness Mediates the Link Between Hypnotizability and Disordered Eating. AB - There has been no research examining why people with disordered eating tend to be highly hypnotizable. The authors examine the hypothesis that concern for appropriateness mediates the association between hypnotizability and disordered eating. Fifty participants aged 15 to 30 completed the Eating Attitudes Test-26 (EAT-26) and the Concern for Appropriateness Scale (CAS) and were administered the Stanford Hypnotic Susceptibility Scale: Form C (SHSS:C). EAT-26 scores predicted CAS scores (beta = 0.24, p < .001), CAS scores predicted SHSS:C scores (beta = 0.38, p < .001), and the mediation model was significant (Sobel Test; R(2) = .24, z = 2.54, p < .01). Individuals with problematic eating attitudes may tend to be more hypnotizable than those with normal eating attitudes at least in part because they are highly influenced by interpersonal messages. PMID- 26894426 TI - The Effect of a Suggestion to Generate Interest in a Reading in Highly Hypnotizable People: A Promising Use in Education. AB - Highly hypnotizable participants in the experimental condition were given a waking state suggestion that a reading not intended to be interesting would be fascinating and remarkable. Controls were given task motivational instructions, in which they were told to try to make it interesting. The suggestion had a major influence on participants' enjoyment of the reading, though no effect was found for reading comprehension. Qualitative interviews indicated that the suggestion had a profound impact on some, especially those most responsive to hypnosis. The lack of an effect in reading comprehension may be due to large within-group variances. Findings suggest that hypnotic suggestion, when properly employed, may have a potential use in enhancing the learning capabilities of highly hypnotizable people. PMID- 26894427 TI - Preparation and Evaluation of Radiolabeled Antibody Recruiting Small Molecules That Target Prostate-Specific Membrane Antigen for Combined Radiotherapy and Immunotherapy. AB - The feasibility of developing a single agent that can deliver radioactive iodine and also direct cellular immune function by engaging endogenous antibodies as an antibody-recruiting small molecule (ARM) was determined. A library of new prostate-specific membrane antigen (PSMA)-binding ligands that contained antibody recruiting 2,4-dinitrophenyl (DNP) groups and iodine were synthesized and screened in vitro and in vivo. A lead compound (9b) showed high affinity for PSMA and the ability to bind anti-DNP antibodies. Biodistribution studies of the iodine-125 analogue showed 3% ID/g in LNCaP xenograft tumors at 1 h postinjection with tumor-to-blood and tumor-to-muscle ratios of 10:1 and 44:1, respectively. The radiolabeled analogue was bound and internalized by LNCaP cells, with both functions blocked using a known PSMA inhibitor. A second candidate showed high tumor uptake (>10% ID/g) but had minimal binding to anti-DNP antibodies. The compounds reported represent the first examples of small molecules developed specifically for combination immunotherapy and radiotherapy for prostate cancer. PMID- 26894428 TI - Relationships Between Stress, Negative Emotions, Resilience, and Smoking: Testing a Moderated Mediation Model. AB - OBJECTIVE: More effective tobacco prevention and cessation programs require in depth understanding of the mechanism by which multiple factors interact with each other to affect smoking behaviors. Stress has long been recognized as a risk factor for smoking. However, the underlying mediation and moderation mechanisms are far from clear. The purpose of this study was to examine the role of negative emotions in mediating the link between stress and smoking and whether this indirect link was modified by resilience. METHODS: Survey data were collected using audio computer-assisted self-interview (ACASI) from a large random sample of urban residents (n = 1249, mean age = 35.1, 45.3% male) in Wuhan, China. Perceived stress, negative emotions (anxiety, depression), resilience were measured with reliable instruments also validated in China. Self-reported smoking was validated with exhaled carbon monoxide. RESULTS: Mediation analysis indicated that two negative emotions fully mediated the link between stress and intensity of smoking (assessed by number of cigarettes smoked per day, effect =.082 for anxiety and.083 for depression) and nicotine dependence (assessed by DSM-IV standard, effect =.134 for anxiety and.207 for depression). Moderated mediation analysis demonstrated that the mediation effects of negative emotions were negatively associated with resilience. CONCLUSIONS: Results suggest resilience interacts with stress and negative emotions to affect the risk of tobacco use and nicotine dependence among Chinese adults. Further research with longitudinal data is needed to verify the findings of this study and to estimate the effect size of resilience in tobacco intervention and cessation programs. PMID- 26894429 TI - Depot-Specific Changes in Fat Metabolism with Aging in a Type 2 Diabetic Animal Model. AB - Visceral fat accretion is a hallmark of aging and is associated with aging induced metabolic dysfunction. PPARgamma agonist was reported to improve insulin sensitivity by redistributing fat from visceral fat to subcutaneous fat. The purpose of this study was to investigate the underlying mechanisms by which aging affects adipose tissue remodeling in a type 2 diabetic animal model and through which PPARgamma activation modulates aging-related fat tissue distribution. At the ages of 21, 31 and 43 weeks, OLETF rats as an animal model of type 2 diabetes were evaluated for aging-related effects on adipose tissue metabolism in subcutaneous and visceral fat depots. During aging, the ratio of visceral fat weight to subcutaneous fat weight (V/S ratio) increased. Aging significantly increased the mRNA expression of genes involved in lipogenesis such as lipoprotein lipase, fatty acid binding protein aP2, lipin 1, and diacylglycerol acyltransferase 1, which were more prominent in visceral fat than subcutaneous fat. The mRNA expression of adipose triglyceride lipase, which is involved in basal lipolysis and fatty acid recycling, was also increased, more in visceral fat compared to subcutaneous fat during aging. The mRNA levels of the genes associated with lipid oxidation were increased, whereas the mRNA levels of genes associated with energy expenditure showed no significant change during aging. PPARgamma agonist treatment in OLETF rats resulted in fat redistribution with a decreasing V/S ratio and improved glucose intolerance. The genes involved in lipogenesis decreased in visceral fat of the PPARgamma agonist-treated rats. During aging, fat distribution was changed by stimulating lipid uptake and esterification in visceral fat rather than subcutaneous fat, and by altering the lipid oxidation. PMID- 26894430 TI - The Cure Rate after Placebo or No Therapy in American Cutaneous Leishmaniasis: A Systematic Review and Meta-Analysis. AB - INTRODUCTION: There are few drugs with proven efficacy in cutaneous leishmaniasis (CL), and pentavalent antimonial derivatives are still the main first-line therapeutic agents worldwide, despite their recognized high toxicities. Randomized controlled clinical trials assessing the efficacy and safety of new therapeutic modalities are of high priority, and the definition of the design of such trials raises debate about the use of placebo as a comparator. To support the use of placebo as a comparator, two main points need to be addressed: 1--the cure rate without any therapeutic intervention and 2--the damage caused by CL and its impact on patients. OBJECTIVE: The aim of this study was to systematically assess the spontaneous cure rate for American CL and to broaden the discussion about placebo use in CL trials. METHODS: The PRISMA guidelines for systematic reviews and the Cochrane manual were followed. The sources used were the PubMed and LILACS databases. Studies were included if they reported cure rates using placebo or no treatment in American CL. RESULTS: Thirteen studies of a total of 352 patients were ultimately included in this review. The summarized global cure rates for all Leishmania species according to the intention-to-treat analyses performed at approximately three ("initial cure") and nine ("definitive cure") months after "no treatment" or placebo use were 26% (CI95%: 16 to 40%) and 26% (CI95%:16 to 38%), respectively. Notably, a significantly lower cure rate was observed for L. braziliensis infection (6.4%, CI95%:0.2 to 20%) than for L. mexicana infection (44%, CI95%:19 to 72%), p = 0.002. Of note, relapse occurred in 20% of patients with initial healing (CI95%:9.2 to 38.9%). CONCLUSION: These results clearly demonstrate a low spontaneous cure rate following no-treatment or placebo use, confirming that this strategy for the control group in CL studies expose patients to greater morbidity, especially for CL caused by L. braziliensis. Therefore, from this point, the crucial question to consider regarding placebo use is the seriousness of the suffering caused by this disease. PMID- 26894431 TI - Lentivirus-Mediated Knockdown of Astrocyte Elevated Gene-1 Inhibits Growth and Induces Apoptosis through MAPK Pathways in Human Retinoblastoma Cells. AB - PURPOSE: To explore expression and function of astrocyte elevated gene-1 (AEG-1) in human retinoblastoma (RB). METHODS: The expression of AEG-1 in histological sections of human RBs and in RB cell lines was examined using immunohistochemical staining and RT-PCR and Western blotting respectively. We knocked down AEG-1 gene levels by AEG-1-siRNA lentivirus transfection of human RB cell lines SO-RB50 and Y79, and using an MTT assay, we assessed the role of AEG-1 on RB cell proliferation. The biological significance of lentivirus transfection induced AEG 1 down-regulation was examined by assessing the apoptosis rate in the transfected RB cells by Annexin V-APC staining and flow cytometry. We additionally measured the expression of Bcl-2, Bax, cleaved-caspase-3 and caspase-3, and the phosphorylation and non-phosphorylation alternation of MAPKs. RESULTS: AEG-1 expression was detected to be strongly positive in the histological slides of 35 out of 54 (65%) patients with RB. AEG-1 expression increased significantly (P<0.05) with tumor stage. In the RB cell lines SO-RB50, Y79 and WERI-RB1 as compared with retinal pigment epithelium cells, expression of AEG-1 mRNA and AEG 1 protein was significantly higher. In AEG-1-siRNA lentivirus transfected cell cultures as compared with negative control lentivirus transfected cell cultures, levels of AEG-1 mRNA and of AEG-1 protein (P<0.05) and cell growth rates (P<0.01) were significantly lower, and apoptosis rate (P<0.001), Bax/Bcl-2 ratio and cleaved-caspase-3 protein level were significantly increased. The P-ERK/ERK ratio was significantly decreased in the AEG-1-siRNA lentivirus transfected cell lines. CONCLUSIONS: Expression of AEG-1 was associated with RB, in histological slides of patients and in cell culture experiments. Lentivirus transfection induced knockdown of AEG-1 had a tumor suppressive effect, potentially by tumor cell apoptosis induction through inhibition of ERK. PMID- 26894432 TI - Heme Oxygenase-1 Expression Affects Murine Abdominal Aortic Aneurysm Progression. AB - Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme degradation, is a cytoprotective enzyme upregulated in the vasculature by increased flow and inflammatory stimuli. Human genetic data suggest that a diminished HO-1 expression may predispose one to abdominal aortic aneurysm (AAA) development. In addition, heme is known to strongly induce HO-1 expression. Utilizing the porcine pancreatic elastase (PPE) model of AAA induction in HO-1 heterozygous (HO-1+/-, HO-1 Het) mice, we found that a deficiency in HO-1 leads to augmented AAA development. Peritoneal macrophages from HO-1+/- mice showed increased gene expression of pro-inflammatory cytokines, including MCP-1, TNF-alpha, IL-1-beta, and IL-6, but decreased expression of anti-inflammatory cytokines IL-10 and TGF beta. Furthermore, treatment with heme returned AAA progression in HO-1 Het mice to a wild-type profile. Using a second murine AAA model (Ang II-ApoE-/-), we showed that low doses of the HMG-CoA reductase inhibitor rosuvastatin can induce HO-1 expression in aortic tissue and suppress AAA progression in the absence of lipid lowering. Our results support those studies that suggest that pleiotropic statin effects might be beneficial in AAA, possibly through the upregulation of HO-1. Specific targeted therapies designed to induce HO-1 could become an adjunctive therapeutic strategy for the prevention of AAA disease. PMID- 26894433 TI - Coenzyme Q10 Levels Are Decreased in the Cerebellum of Multiple-System Atrophy Patients. AB - BACKGROUND: The objective of this study was to evaluate whether the levels of coenzyme Q10 (CoQ10) in brain tissue of multiple system atrophy (MSA) patients differ from those in elderly controls and in patients with other neurodegenerative diseases. METHODS: Flash frozen brain tissue of a series of 20 pathologically confirmed MSA patients [9 olivopontocerebellar atrophy (OPCA) type, 6 striatonigral degeneration (SND) type, and 5 mixed type] was used for this study. Elderly controls (n = 37) as well as idiopathic Parkinson's disease (n = 7), dementia with Lewy bodies (n = 20), corticobasal degeneration (n = 15) and cerebellar ataxia (n = 18) patients were used as comparison groups. CoQ10 was measured in cerebellar and frontal cortex tissue by high performance liquid chromatography. RESULTS: We detected a statistically significant decrease (by 3 5%) in the level of CoQ10 in the cerebellum of MSA cases (P = 0.001), specifically in OPCA (P = 0.001) and mixed cases (P = 0.005), when compared to controls as well as to other neurodegenerative diseases [dementia with Lewy bodies (P<0.001), idiopathic Parkinson's disease (P<0.001), corticobasal degeneration (P<0.001), and cerebellar ataxia (P = 0.001)]. CONCLUSION: Our results suggest that a perturbation in the CoQ10 biosynthetic pathway is associated with the pathogenesis of MSA but the mechanism behind this finding remains to be elucidated. PMID- 26894434 TI - Model Development for Risk Assessment of Driving on Freeway under Rainy Weather Conditions. AB - Rainy weather conditions could result in significantly negative impacts on driving on freeways. However, due to lack of enough historical data and monitoring facilities, many regions are not able to establish reliable risk assessment models to identify such impacts. Given the situation, this paper provides an alternative solution where the procedure of risk assessment is developed based on drivers' subjective questionnaire and its performance is validated by using actual crash data. First, an ordered logit model was developed, based on questionnaire data collected from Freeway G15 in China, to estimate the relationship between drivers' perceived risk and factors, including vehicle type, rain intensity, traffic volume, and location. Then, weighted driving risk for different conditions was obtained by the model, and further divided into four levels of early warning (specified by colors) using a rank order cluster analysis. After that, a risk matrix was established to determine which warning color should be disseminated to drivers, given a specific condition. Finally, to validate the proposed procedure, actual crash data from Freeway G15 were compared with the safety prediction based on the risk matrix. The results show that the risk matrix obtained in the study is able to predict driving risk consistent with actual safety implications, under rainy weather conditions. PMID- 26894435 TI - Correction: Wolbachia in European Populations of the Invasive Pest Drosophila suzukii: Regional Variation in Infection Frequencies. PMID- 26894436 TI - Spatial-Temporal Distribution of Hantavirus Rodent-Borne Infection by Oligoryzomys fulvescens in the Agua Buena Region--Panama. AB - BACKGROUND: Hotspot detection and characterization has played an increasing role in understanding the maintenance and transmission of zoonotic pathogens. Identifying the specific environmental factors (or their correlates) that influence reservoir host abundance help increase understanding of how pathogens are maintained in natural systems and are crucial to identifying disease risk. However, most recent studies are performed at macro-scale and describe broad temporal patterns of population abundances. Few have been conducted at a microscale over short time periods that better capture the dynamical patterns of key populations. These finer resolution studies may better define the likelihood of local pathogen persistence. This study characterizes the landscape distribution and spatio-temporal dynamics of Oligoryzomys fulvescens (O. fulvescens), an important mammalian reservoir in Central America. METHODS: Information collected in a longitudinal study of rodent populations in the community of Agua Buena in Tonosi, Panama, between April 2006 and December 2009 was analyzed using non-spatial analyses (box plots) and explicit spatial statistical tests (correlograms, SADIE and LISA). A 90 node grid was built (raster format) to design a base map. The area between the nodes was 0.09 km(2) and the total study area was 6.43 km(2) (2.39 x 2.69 km). The temporal assessment dataset was divided into four periods for each year studied: the dry season, rainy season, and two months-long transitions between seasons (the months of April and December). RESULTS: There were heterogeneous patterns in the population densities and degrees of dispersion of O. fulvescens that varied across seasons and among years. The species typically was locally absent during the late transitional months of the season, and re-established locally in subsequent years. These populations re-occurred in the same area during the first three years but subsequently re-established further south in the final year of the study. Spatial autocorrelation analyses indicated local populations encompassed approximately 300-600 m. The borders between suitable and unsuitable habitats were sharply demarcated over short distances. CONCLUSION: Oligoryzomys fulvescens showed a well-defined spatial pattern that evolved over time, and led to a pattern of changing aggregation. Thus, hot spots of abundance showed a general shifting pattern that helps explain the intermittent risk from pathogens transmitted by this species. This variation was associated with seasonality, as well as anthropogenic pressures that occurred with agricultural activities. These factors help define the characteristics of the occurrence, timing, intensity and duration of synanthropic populations affected by human populations and, consequently, possible exposure that local human populations experience. PMID- 26894437 TI - Electroacupuncture Produces the Sustained Motor Improvement in 6-Hydroxydopamine Lesioned Mice. AB - Clinical and research evidence has shown that electroacupuncture (EA) promotes recovery of motor function in patients with Parkinson's disease (PD). However, the "efficacy span" of EA treatment, especially the long-term effect of EA that is thought to last after the cessation of EA treatment, has not been investigated. The present study thus investigated and compared the effect of EA during and after chronic EA application on motor activity and dopamine lesions in a 6-hydroxydopamine (6-OHDA)-lesioned mouse model of PD. Chronic EA treatment (30 min a day, 6 days a week for 2 or 4 weeks) significantly attenuated motor deficiency and reduced dopamine neuron degeneration. Remarkably, EA showed a long lasting effect after the cessation of EA stimulation. At 2 and 4 weeks after the termination of EA, EA continued to improve motor function in 6-OHDA-lesioned mice. Consistent with sustained behavioral effects, EA induced an enduring increase in the dopamine turnover ratio in the striatum 2 weeks after the cessation of EA treatment. Here we demonstrated that the therapeutic effect of EA outlasted the duration of EA application. During a relatively long period of time after the completion of EA treatment, EA is able to continue to improve motor function and enhance dopamine availability in 6-OHDA-lesioned PD mice. PMID- 26894438 TI - Problematic Internet Users' Discounting Behaviors Reflect an Inability to Delay Gratification, Not Risk Taking. AB - The relationship between impulse control disorder (ICD) behaviors and problematic Internet use (PIU) has been established in the literature. Our aim was to further investigate whether the ICDs of individuals suffering from PIU primarily involve an inability to delay gratification or a tendency to take risks. Using delay and probability discounting tasks, we compared the subjective value of discounting between PIU individuals and controls in conditions of gaining or losing different monetary amounts. The results of the present study revealed a significant positive relationship between PIU and impulsivity scores. PIU individuals discounted delayed amounts more steeply than controls, regardless of the reward sign and monetary amount. Conversely, there were no significant group differences in the probability discounting task. These findings suggest that PIU individuals may be more impulsive than controls when impulsivity is framed as insensitivity to delayed outcomes rather than as a tendency to take risks, which is inconsistent with the view of impulsivity as a general trait. PMID- 26894439 TI - Tuning and Erasing Surface Wrinkles by Reversible Visible-Light-Induced Photoisomerization. AB - Periodic wrinkling across different scales has received considerable attention because it not only represents structure failure but also finds wide applications. How to prevent wrinkling or create desired wrinkling patterns is non-trivial because the dynamic evolution of wrinkles is a highly nonlinear problem. Herein, we report a simple yet powerful method to dynamically tune and/or erase wrinkling patterns with visible light. The light-induced photoisomerization of azobenzene units in azopolymer films leads to stress release and consequently to the erasure of the wrinkles. The wrinkles in unexposed regions are also affected and oriented perpendicular to the exposed boundary during the stress reorganization. Theoretical models were developed to understand the dynamics of the reversible photoisomerization-induced wrinkle evolution. This method can be applied for designing functional materials/devices, for example, for the reversible optical writing/erasure of information as demonstrated here. PMID- 26894440 TI - Gas-Phase Studies of Formamidopyrimidine Glycosylase (Fpg) Substrates. AB - Gas-phase thermochemical properties (tautomerism, acidity, and proton affinity) have been measured and calculated for a series of nucleobase derivatives that have not heretofore been examined under vacuum. The studied species are substrates for the enzyme formamidopyrimidine glycosylase (Fpg), which cleaves damaged nucleobases from DNA. The gas-phase results are compared and contrasted to solution-phase data, to afford insight into the Fpg mechanism. Calculations are also used to probe the energetics of various possible mechanisms and to predict isotope effects that could potentially allow for discrimination between different mechanisms. Specifically, (18) O substitution at the ribose O4' is predicted to result in a normal kinetic isotope effect (KIE) for a ring-opening "endocyclic" mechanism and an inverse KIE for a direct base excision "exocyclic" pathway. PMID- 26894443 TI - The Ulnar Nerve at Elbow Extension and Flexion: Assessment of Position and Signal Intensity on MR Images. AB - Purpose To assess the position and signal intensity of the ulnar nerve at elbow extension and flexion by using magnetic resonance imaging. Materials and Methods Institutional review board approval and written informed consent were obtained. Transverse T2-weighted images were obtained perpendicular to the upper arm in 100 healthy elbows of 50 volunteers (23 men, 27 women; age range, 21-57 years) and nine elbows with ulnar neuropathy (five men, four women; age range, 24-59 years) with extension and 130 degrees of flexion. Ulnar nerve position was classified into three types: no dislocation, subluxation, or dislocation. One-way analysis of variance, paired t tests, Student t tests, and multiple regression analysis were used to analyze correlations between ulnar nerve movement angle during flexion and age, sex, presence of the anconeus epitrochlearis muscle, and ulnar neuropathy and to compare the contrast-to-noise ratio of nerve to muscle between extension and flexion. Results Nerve positions in healthy elbows were as follows: All had no dislocation at extension, and at flexion, 51 of 100 elbows (51.0%) had no dislocation, 30 of 100 elbows (30.0%) had subluxation, and 19 of 100 elbows (19.0%) had dislocation. Nerve movement angle was smaller in elbows with the anconeus epitrochlearis muscle than in those without the muscle (P = .045, .015). Presence of the muscle was the only significant factor associated with nerve movement angle (P = .047, .013). Only dominant elbows with nerve movement angle of less than 15 degrees and nondominant elbows with nerve movement angle of less than 10 degrees showed contrast-to-noise ratio increase at flexion (P = .021 .030). Conclusion Ulnar nerve movement during flexion was apparent in approximately half of healthy elbows and was similar between healthy elbows and elbows with ulnar neuropathy. Nerve signal intensity increased during flexion only in elbows without apparent nerve movement. ((c)) RSNA, 2016 Online supplemental material is available for this article. PMID- 26894442 TI - Bioactivity of a Rice Bran-Derived Peptide and its Sensory Evaluation and Storage Stability in Orange Juice. AB - A pentapeptide prepared from rice bran demonstrated growth inhibition on human lung, liver, breast, and colon cancer cell lines. The objectives of this study were to evaluate the human prostate cancer growth inhibition by the pentapeptide and its 6-mo storage stability by incorporating spray-dried orange juice, and determining sensory acceptability. The pentapeptide showed inhibition of human prostate cancer cells by 45% at 460 MUg/mL concentration. When incorporated in spray-dried orange juice, and reconstituted with water and tested, there was an approximately 10% degradation of the peptide at 620 MUg/mL concentration under refrigerated conditions over a 6 mo storage period, whereas at ambient temperature the degradation was 30%. Larger degradation was observed when 240 or 460 MUg/mL pentapeptide was used. Overall, consumer panelists liked sensory aspect of the reconstituted pentapeptide incorporated orange juice beverage. Also consumer panelists liked the color and mouthfeel attributes, their hedonic impression of flavor attribute was slightly low due to unpalatable bitter note caused by the presence of the peptide. Incorporation of the pentapeptide in spray dried orange juice has the potential to serve as a functional food ingredient that can offer health benefits to consumers. It is possible that the structural instability can be minimized by encapsulation. PMID- 26894444 TI - Accurate thickness measurement of graphene. AB - Graphene has emerged as a material with a vast variety of applications. The electronic, optical and mechanical properties of graphene are strongly influenced by the number of layers present in a sample. As a result, the dimensional characterization of graphene films is crucial, especially with the continued development of new synthesis methods and applications. A number of techniques exist to determine the thickness of graphene films including optical contrast, Raman scattering and scanning probe microscopy techniques. Atomic force microscopy (AFM), in particular, is used extensively since it provides three dimensional images that enable the measurement of the lateral dimensions of graphene films as well as the thickness, and by extension the number of layers present. However, in the literature AFM has proven to be inaccurate with a wide range of measured values for single layer graphene thickness reported (between 0.4 and 1.7 nm). This discrepancy has been attributed to tip-surface interactions, image feedback settings and surface chemistry. In this work, we use standard and carbon nanotube modified AFM probes and a relatively new AFM imaging mode known as PeakForce tapping mode to establish a protocol that will allow users to accurately determine the thickness of graphene films. In particular, the error in measuring the first layer is reduced from 0.1-1.3 nm to 0.1-0.3 nm. Furthermore, in the process we establish that the graphene-substrate adsorbate layer and imaging force, in particular the pressure the tip exerts on the surface, are crucial components in the accurate measurement of graphene using AFM. These findings can be applied to other 2D materials. PMID- 26894441 TI - New methods to image transcription in living fly embryos: the insights so far, and the prospects. AB - The regulation of transcription is a fundamental process underlying the determination of cell identity and its maintenance during development. In the last decades, most of the transcription factors, which have to be expressed at the right place and at the right time for the proper development of the fly embryo, have been identified. However, mostly because of the lack of methods to visualize transcription as the embryo develops, their coordinated spatiotemporal dynamics remains largely unexplored. Efforts have been made to decipher the transcription process with single molecule resolution at the single cell level. Recently, the fluorescent labeling of nascent RNA in developing fly embryos allowed the direct visualization of ongoing transcription at single loci within each nucleus. Together with powerful imaging and quantitative data analysis, these new methods provide unprecedented insights into the temporal dynamics of the transcription process and its intrinsic noise. Focusing on the Drosophila embryo, we discuss how the detection of single RNA molecules enhanced our comprehension of the transcription process and we outline the potential next steps made possible by these new imaging tools. In combination with genetics and theoretical analysis, these new imaging methods will aid the search for the mechanisms responsible for the robustness of development. For further resources related to this article, please visit the WIREs website. PMID- 26894445 TI - Functional metagenomic screen reveals new and diverse microbial rhodopsins. AB - Ion-translocating retinylidene rhodopsins are widely distributed among marine and freshwater microbes. The translocation is light-driven, contributing to the production of biochemical energy in diverse microbes. Until today, most microbial rhodopsins had been detected using bioinformatics based on homology to other rhodopsins. In the past decade, there has been increased interest in microbial rhodopsins in the field of optogenetics since microbial rhodopsins were found to be most useful in vertebrate neuronal systems. Here we report on a functional metagenomic assay for detecting microbial rhodopsins. Using an array of narrow pH electrodes and light-emitting diode illumination, we were able to screen a metagenomic fosmid library to detect diverse marine proteorhodopsins and an actinorhodopsin based solely on proton-pumping activity. Our assay therefore provides a rather simple phenotypic means to enrich our understanding of microbial rhodopsins without any prior knowledge of the genomic content of the environmental entities screened. PMID- 26894446 TI - A robust nitrifying community in a bioreactor at 50 degrees C opens up the path for thermophilic nitrogen removal. AB - The increasing production of nitrogen-containing fertilizers is crucial to meet the global food demand, yet high losses of reactive nitrogen associated with the food production/consumption chain progressively deteriorate the natural environment. Currently, mesophilic nitrogen-removing microbes eliminate nitrogen from wastewaters. Although thermophilic nitrifiers have been separately enriched from natural environments, no bioreactors are described that couple these processes for the treatment of nitrogen in hot wastewaters. Samples from composting facilities were used as inoculum for the batch-wise enrichment of thermophilic nitrifiers (350 days). Subsequently, the enrichments were transferred to a bioreactor to obtain a stable, high-rate nitrifying process (560 days). The community contained up to 17% ammonia-oxidizing archaea (AOAs) closely related to 'Candidatus Nitrososphaera gargensis', and 25% nitrite-oxidizing bacteria (NOBs) related to Nitrospira calida. Incorporation of (13)C-derived bicarbonate into the respective characteristic membrane lipids during nitrification supported their activity as autotrophs. Specific activities up to 198+/-10 and 894+/-81 mg N g(-1) VSS per day for AOAs and NOBs were measured, where NOBs were 33% more sensitive to free ammonia. The NOBs were extremely sensitive to free nitrous acid, whereas the AOAs could only be inhibited by high nitrite concentrations, independent of the free nitrous acid concentration. The observed difference in product/substrate inhibition could facilitate the development of NOB inhibition strategies to achieve more cost-effective processes such as deammonification. This study describes the enrichment of autotrophic thermophilic nitrifiers from a nutrient-rich environment and the successful operation of a thermophilic nitrifying bioreactor for the first time, facilitating opportunities for thermophilic nitrogen removal biotechnology. PMID- 26894447 TI - Resource-dependent attenuation of species interactions during bacterial succession. AB - Bacterial communities are vital for many economically and ecologically important processes. The role of bacterial community composition in determining ecosystem functioning depends critically on interactions among bacterial taxa. Several studies have shown that, despite a predominance of negative interactions in communities, bacteria are able to display positive interactions given the appropriate evolutionary or ecological conditions. We were interested in how interspecific interactions develop over time in a naturalistic setting of low resource supply rates. We assembled aquatic bacterial communities in microcosms and assayed the productivity (respiration and growth) and substrate degradation while tracking community composition. The results demonstrated that while bacterial communities displayed strongly negative interactions during the early phase of colonisation and acclimatisation to novel biotic and abiotic factors, this antagonism declined over time towards a more neutral state. This was associated with a shift from use of labile substrates in early succession to use of recalcitrant substrates later in succession, confirming a crucial role of resource dynamics in linking interspecific interactions with ecosystem functioning. PMID- 26894450 TI - Topical carbonic anhydrase inhibitors in macular edema associated with Alstrom syndrome. AB - BACKGROUND: Alstrom syndrome is a rare genetic ciliopathy caused by a mutation in the ALMS1 gene. The syndrome is characterized by cone-rod dystrophy, dilated myocardiopathy, childhood obesity and sensorineural hearing loss. To date, cystoid macular edema has not been reported. METHODS: A female affected by Alstrom syndrome developed bilateral cystoid macular edema evidenced by optical coherence tomography. A topical carbonic anhydrase inhibitor was prescribed. RESULTS: Complete resolution of the cystoid macular edema was achieved, though visual acuity did not improve. CONCLUSIONS: Topical carbonic anhydrase inhibitors may have a role in the treatment of macular edema in syndromic retinal dystrophies such as Alstrom syndrome. PMID- 26894448 TI - Insect pathogenicity in plant-beneficial pseudomonads: phylogenetic distribution and comparative genomics. AB - Bacteria of the genus Pseudomonas occupy diverse environments. The Pseudomonas fluorescens group is particularly well-known for its plant-beneficial properties including pathogen suppression. Recent observations that some strains of this group also cause lethal infections in insect larvae, however, point to a more versatile ecology of these bacteria. We show that 26 P. fluorescens group strains, isolated from three continents and covering three phylogenetically distinct sub-clades, exhibited different activities toward lepidopteran larvae, ranging from lethal to avirulent. All strains of sub-clade 1, which includes Pseudomonas chlororaphis and Pseudomonas protegens, were highly insecticidal regardless of their origin (animals, plants). Comparative genomics revealed that strains in this sub-clade possess specific traits allowing a switch between plant and insect-associated lifestyles. We identified 90 genes unique to all highly insecticidal strains (sub-clade 1) and 117 genes common to all strains of sub clade 1 and present in some moderately insecticidal strains of sub-clade 3. Mutational analysis of selected genes revealed the importance of chitinase C and phospholipase C in insect pathogenicity. The study provides insight into the genetic basis and phylogenetic distribution of traits defining insecticidal activity in plant-beneficial pseudomonads. Strains with potent dual activity against plant pathogens and herbivorous insects have great potential for use in integrated pest management for crops. PMID- 26894451 TI - The Role of Anti-U1 RNP Positivity in Predicting Survival in Patients With Connective Tissue Disease-Associated Pulmonary Arterial Hypertension: Angel or Demon? Comment on the Article by Sobanski et al. PMID- 26894452 TI - Controllable dissociations of PH3 molecules on Si(001). AB - We demonstrate for the first time to our knowledge that controllable dissociation of PH3 adsorption products PHx (x = 2, 1) can be realized by STM (scanning tunneling microscope) manipulation techniques at room temperature. Five dissociative products and their geometric structures are identified via combining STM experiments and first-principle calculations and simulations. In total we realize nine kinds of controllable dissociations by applying a voltage pulse among the PH3-related structures on Si(001). The dissociation rates of the five most common reactions are measured by the I-t spectrum method as a function of voltage. The suddenly increased dissociation rate at 3.3 V indicates a transition from multivibrational excitation to single-step excitation induced by inelastic tunneling electrons. Our studies prove that selectively breaking the chemical bonds of a single molecule on semiconductor surface by STM manipulation technique is feasible. PMID- 26894453 TI - Construction of Chinese adult male phantom library and its application in the virtual calibration of in vivo measurement. AB - In vivo measurement is a main method of internal contamination evaluation, particularly for large numbers of people after a nuclear accident. Before the practical application, it is necessary to obtain the counting efficiency of the detector by calibration. The virtual calibration based on Monte Carlo simulation usually uses the reference human computational phantom, and the morphological difference between the monitored personnel with the calibrated phantom may lead to the deviation of the counting efficiency. Therefore, a phantom library containing a wide range of heights and total body masses is needed. In this study, a Chinese reference adult male polygon surface (CRAM_S) phantom was constructed based on the CRAM voxel phantom, with the organ models adjusted to match the Chinese reference data. CRAM_S phantom was then transformed to sitting posture for convenience in practical monitoring. Referring to the mass and height distribution of the Chinese adult male, a phantom library containing 84 phantoms was constructed by deforming the reference surface phantom. Phantoms in the library have 7 different heights ranging from 155 cm to 185 cm, and there are 12 phantoms with different total body masses in each height. As an example of application, organ specific and total counting efficiencies of Ba-133 were calculated using the MCNPX code, with two series of phantoms selected from the library. The influence of morphological variation on the counting efficiency was analyzed. The results show only using the reference phantom in virtual calibration may lead to an error of 68.9% for total counting efficiency. Thus the influence of morphological difference on virtual calibration can be greatly reduced using the phantom library with a wide range of masses and heights instead of a single reference phantom. PMID- 26894454 TI - Perioperative seizure in patients with glioma is associated with longer hospitalization, higher readmission, and decreased overall survival. AB - OBJECTIVE Seizures are among the most common perioperative complications in patients undergoing craniotomy for brain tumor resection and have been associated with increased disease progression and decreased survival. Little evidence exists regarding the relationship between postoperative seizures and hospital quality measures, including length of stay (LOS), disposition, and readmission. The authors sought to address these questions by analyzing a glioma population over 15 years. METHODS A retrospective cohort study was used to evaluate the outcomes of patients who experienced a postoperative seizure. Patients with glioma who underwent craniotomy for resection between 1998 and 2013 were enrolled in the institutional tumor registry. Basic data, including demographics and comorbidities, were recorded in addition to hospitalization details and complications. Seizures were diagnosed by clinical examination, observation, and electroencephalography. The Student t-test and chi-square test were used to analyze differences in the means between continuous and categorical variables, respectively. Multivariate logistic and linear regression was used to compare multiple clinical variables against hospital quality metrics and survival figures, respectively. RESULTS In total, 342 patients with glioma underwent craniotomy for first-time resection. The mean age was 51.0 +/- 17.3 years, 192 (56.1%) patients were male, and the median survival time for all grades was 15.4 months (range 6.2-24.0 months). High-grade glioma (Grade III or IV) was seen in 71.9% of patients. Perioperative antiepileptic drugs were administered to 88% of patients. Eighteen (5.3%) patients experienced a seizure within 14 days postoperatively, and 9 (50%) of these patients experienced first-time seizures. The mean time to the first postoperative seizure was 4.3 days (range 0-13 days). There was no significant association between tumor grade and the rate of perioperative seizure (Grade I, 0%; II, 7.0%; III, 6.1%; IV, 5.2%; p = 0.665). A single ictal episode occurred in 11 patients, while 3 patients experienced 2 seizures and 4 patients developed 3 or more seizures. Compared with their seizure free counterparts, patients who experienced a perioperative seizure had an increased average hospital (6.8 vs 3.6 days, p = 0.032) and ICU LOS (5.4 vs 2.3 days; p < 0.041). Seventy-five percent of seizure-free patients were discharged home in comparison with 55.6% of seizure patients (p = 0.068). Patients with a postoperative seizure were significantly more likely to visit the emergency department within 90 days (44.4% vs 19.0%; OR 3.41 [95% CI 1.29-9.02], p = 0.009) and more likely to be readmitted within 90 days (50.0% vs 18.4%; OR 4.45 [95% CI 1.69-11.70], p = 0.001). In addition, seizure-free patients had a longer median overall survival (15.6 months [interquartile range 6.6-24.4 months] vs 3.0 months [interquartile range 1.0-25.0 months]; p = 0.013). CONCLUSIONS Patients with perioperative seizures following glioma resection required longer hospital and ICU LOS, were readmitted at higher rates than seizure-free patients, and experienced shorter overall survival. Biological and clinical factors that predispose to the development of seizures after glioma surgery portend a worse outcome. Efforts to identify these factors and reduce the risk of postoperative seizure should remain a priority among neurosurgical oncologists. PMID- 26894455 TI - Sir Hugh Cairns and World War II British advances in head injury management, diffuse brain injury, and concussion: an Oxford tale. AB - The authors trace the Oxford, England, roots of World War II (WWII)-related advances in head injury management, the biomechanics of concussion and brain injury, and postwar delineation of pathological findings in severe concussion and diffuse brain injury in man. The prominent figure in these developments was the charismatic and innovative Harvey Cushing-trained neurosurgeon Sir Hugh Cairns. Cairns, who was to closely emulate Cushing's surgical and scholarly approach, is credited with saving thousands of lives during WWII by introducing and implementing innovative programs such as helmets for motorcyclists, mobile neurosurgical units near battle zones, and the military usage of penicillin. In addition, he inspired and taught a generation of neurosurgeons, neurologists, and neurological nurses in the care of brain and spinal cord injuries at Oxford's Military Hospital for Head Injuries. During this time Cairns also trained the first full-time female neurosurgeon. Pivotal in supporting animal research demonstrating the critical role of acceleration in the causation of concussion, Cairns recruited the physicist Hylas Holbourn, whose research implicated rotary acceleration and shear strains as particularly damaging. Cairns' work in military medicine and head injury remain highly influential in efforts to mitigate and manage brain injury. PMID- 26894456 TI - Clinical implications of the cortical hyperintensity belt sign in fluid attenuated inversion recovery images after bypass surgery for moyamoya disease. AB - OBJECTIVE Transient neurological symptoms are frequently observed during the early postoperative period after direct bypass surgery for moyamoya disease. Abnormal signal changes in the cerebral cortex can be seen in postoperative MR images. The purpose of this study was to reveal the radiological features of the "cortical hyperintensity belt (CHB) sign" in postoperative FLAIR images and to verify its relationship to transient neurological events (TNEs) and regional cerebral blood flow (rCBF). METHODS A total of 141 hemispheres in 107 consecutive patients with moyamoya disease who had undergone direct bypass surgery were analyzed. In all cases, FLAIR images were obtained during postoperative days (PODs) 1-3 and during the chronic period (3.2 +/- 1.13 months after surgery). The CHB sign was defined as an intraparenchymal high-intensity signal within the cortex of the surgically treated hemisphere with no infarction or hemorrhage present. The territory of the middle cerebral artery was divided into anterior and posterior parts, with the extent of the CHB sign in each part scored as 0 for none; 1 for presence in less than half of the part; and 2 for presence in more than half of the part. The sum of these scores provided the CHB score (0-4). TNEs were defined as reversible neurological deficits detected both objectively and subjectively. The rCBF was measured with SPECT using N-isopropyl-p [123I]iodoamphetamine before surgery and during PODs 1-3. The rCBF increase ratio was calculated by comparing the pre- and postoperative count activity. RESULTS Cortical hyperintensity belt signs were detected in 112 cases (79.4%) and all disappeared during the chronic period. Although all bypass grafts were anastomosed to the anterior part of the middle cerebral artery territory, CHB signs were much more pronounced in the posterior part (p < 0.0001). TNEs were observed in 86 cases (61.0%). Patients with TNEs showed significantly higher CHB scores than those without (2.31 +/- 0.13 vs 1.24 +/- 0.16, p < 0.0001). The CHB score, on the other hand, showed no relationship with the rCBF increase ratio (p = 0.775). In addition, the rCBF increase ratio did not differ between those patients with TNEs and those without (1.15 +/- 0.033 vs 1.16 +/- 0.037, p = 0.978). CONCLUSIONS The findings strongly suggest that the presence of the CHB sign during PODs 1-3 can be a predictor of TNEs after bypass surgery for moyamoya disease. On the other hand, presence of this sign appears to have no direct relationship with the postoperative local hyperperfusion phenomenon. Vasogenic edema can be hypothesized as the pathophysiology of the CHB sign, because the sign was transient and never accompanied by infarction in the present series. PMID- 26894457 TI - Stereotactic probability and variability of speech arrest and anomia sites during stimulation mapping of the language dominant hemisphere. AB - OBJECTIVE Functional mapping using direct cortical stimulation is the gold standard for the prevention of postoperative morbidity during resective surgery in dominant-hemisphere perisylvian regions. Its role is necessitated by the significant interindividual variability that has been observed for essential language sites. The aim in this study was to determine the statistical probability distribution of eliciting aphasic errors for any given stereotactically based cortical position in a patient cohort and to quantify the variability at each cortical site. METHODS Patients undergoing awake craniotomy for dominant-hemisphere primary brain tumor resection between 1999 and 2014 at the authors' institution were included in this study, which included counting and picture-naming tasks during dense speech mapping via cortical stimulation. Positive and negative stimulation sites were collected using an intraoperative frameless stereotactic neuronavigation system and were converted to Montreal Neurological Institute coordinates. Data were iteratively resampled to create mean and standard deviation probability maps for speech arrest and anomia. Patients were divided into groups with a "classic" or an "atypical" location of speech function, based on the resultant probability maps. Patient and clinical factors were then assessed for their association with an atypical location of speech sites by univariate and multivariate analysis. RESULTS Across 102 patients undergoing speech mapping, the overall probabilities of speech arrest and anomia were 0.51 and 0.33, respectively. Speech arrest was most likely to occur with stimulation of the posterior inferior frontal gyrus (maximum probability from individual bin = 0.025), and variance was highest in the dorsal premotor cortex and the posterior superior temporal gyrus. In contrast, stimulation within the posterior perisylvian cortex resulted in the maximum mean probability of anomia (maximum probability = 0.012), with large variance in the regions surrounding the posterior superior temporal gyrus, including the posterior middle temporal, angular, and supramarginal gyri. Patients with atypical speech localization were far more likely to have tumors in canonical Broca's or Wernicke's areas (OR 7.21, 95% CI 1.67-31.09, p < 0.01) or to have multilobar tumors (OR 12.58, 95% CI 2.22 71.42, p < 0.01), than were patients with classic speech localization. CONCLUSIONS This study provides statistical probability distribution maps for aphasic errors during cortical stimulation mapping in a patient cohort. Thus, the authors provide an expected probability of inducing speech arrest and anomia from specific 10-mm2 cortical bins in an individual patient. In addition, they highlight key regions of interindividual mapping variability that should be considered preoperatively. They believe these results will aid surgeons in their preoperative planning of eloquent cortex resection. PMID- 26894458 TI - Chronic spatial working memory deficit associated with the superior longitudinal fasciculus: a study using voxel-based lesion-symptom mapping and intraoperative direct stimulation in right prefrontal glioma surgery. AB - OBJECTIVE Although the right prefrontal region is regarded as a silent area, chronic deficits of the executive function, including working memory (WM), could occur after resection of a right prefrontal glioma. This may be overlooked by postoperative standard examinations, and the disabilities could affect the patient's professional life. The right prefrontal region is a part of the frontoparietal network and is subserved by the superior longitudinal fasciculus (SLF); however, the role of the SLF in spatial WM is unclear. This study investigated a persistent spatial WM deficit in patients who underwent right prefrontal glioma resection, and evaluated the relationship between the spatial WM deficit and the SLF. METHODS Spatial WM was examined in 24 patients who underwent prefrontal glioma resection (right, n = 14; left, n = 10) and in 14 healthy volunteers using a spatial 2-back task during the long-term postoperative period. The neural correlates of spatial WM were evaluated using lesion mapping and voxel-based lesion-symptom mapping. In addition, the spatial 2-back task was performed during surgery under direct subcortical electrical stimulation in 2 patients with right prefrontal gliomas. RESULTS Patients with a right prefrontal lesion had a significant chronic spatial WM deficit. Voxel-based lesion-symptom mapping analysis revealed a significant correlation between spatial WM deficit and the region that overlapped the first and second segments of the SLF (SLF I and SLF II). Two patients underwent awake surgery and had difficulties providing the correct responses in the spatial 2-back task with direct subcortical electrical stimulation on the SLF I, which was preserved and confirmed by postoperative diffusion tensor imaging tractography. These patients exhibited no spatial WM deficits during the postoperative immediate and long-term periods. CONCLUSIONS Spatial WM deficits may persist in patients who undergo resection of the tumor located in the right prefrontal brain parenchyma. Injury to the dorsal frontoparietal subcortical white matter pathway, i.e., the SLF I or SLF I and II, could play a causal role in this chronic deficit. A persistent spatial WM deficit, without motor and language deficits, could affect the professional life of the patient. In such cases, awake surgery would be useful to detect the spatial WM network with appropriate task during tumor exploration. PMID- 26894459 TI - Acute deep brain stimulation changes in regional cerebral blood flow in obsessive compulsive disorder. AB - OBJECTIVE Deep brain stimulation (DBS) is a reversible, nonlesion-based treatment for patients with intractable obsessive-compulsive disorder (OCD). The first studies on DBS for OCD stimulating the ventral capsule/ventral striatum (VC/VS) yielded encouraging results for this neuroanatomical site's therapeutic efficacy. This investigation was conducted to better understand which regions of the cortico-striatal-thalamic-cortical network were acutely affected by VC/VS DBS for OCD. Furthermore, the objective was to identify which brain regions demonstrated changes in perfusion, as stimulation was applied across a dorsoventral lead axis that corresponded to different anatomical locations in the VC/VS. METHODS Six patients receiving VC/VS DBS for OCD underwent oxygen-15 positron emission tomography (15O-PET) scanning. Monopolar DBS was delivered at each of the 4 different electrodes on the stimulating lead in the VC/VS. The data were analyzed using SPM5. Paired t-tests were run in SPSS to identify significant changes in regional cerebral blood flow (rCBF) between stimulation conditions. Pearson's r correlations were run between these significant changes in rCBF and changes in OCD and depressive symptom severity. RESULTS Perfusion in the dorsal anterior cingulate cortex (dACC) significantly increased when monopolar DBS was turned on at the most ventral DBS contact, and this increase in dACC activity was correlated with reductions in depressive symptom severity (r(5) = -0.994, p = 0.001). Perfusion in the thalamus, striatum, and globus pallidus significantly increased when DBS was turned on at the most dorsal contact. CONCLUSIONS DBS of the VC/VS appears to modulate activity in the regions implicated in the pathophysiology of OCD. Different regions in the cortico-striatal-thalamic cortical circuit showed increased perfusion based on whether the stimulation was more ventral or dorsal along the lead axis in the VC/VS. Evidence was found that DBS at the most ventral site was associated with clinical changes in depressive symptom severity, but not OCD symptom severity. PMID- 26894460 TI - Letter to the Editor: Bibliometric profiles for US neurosurgical residency programs. PMID- 26894461 TI - Letter to the Editor: Low-flow bypass and wrap-clipping for ruptured blister aneurysms of the ICA. PMID- 26894462 TI - Clipping of previously coiled cerebral aneurysms: efficacy, safety, and predictors in a cohort of 111 patients. AB - OBJECTIVE With the increasing number of aneurysms treated with endovascular coiling, more recurrences are being encountered. The aim of this study was to evaluate the efficacy and safety of microsurgical clipping in the treatment of recurrent, previously coiled cerebral aneurysms and to identify risk factors that can affect the outcomes of this procedure. METHODS One hundred eleven patients with recurrent aneurysms whose lesions were managed by surgical clipping between January 2002 and October 2014 were identified. The rates of aneurysm occlusion, retreatment, complications, and good clinical outcome were retrospectively determined. Univariate and multivariate logistic regressions were performed to identify factors associated with these outcomes. RESULTS The mean patient age was 50.5 years, the mean aneurysm size was 7 mm, and 97.3% of aneurysms were located in the anterior circulation. The mean follow-up was 22 months. Complete aneurysm occlusion, as assessed by intraoperative angiography, was achieved in 97.3% of aneurysms (108 of 111 patients). Among patients, 1.8% (2 of 111 patients) had a recurrence after clipping. Retreatment was required in 4.5% of patients (5 of 111) after clipping. Major complications were observed in 8% of patients and mortality in 2.7%. Ninety percent of patients had a good clinical outcome. Aneurysm size (OR 1.4, 95% CI 1.08-1.7; p = 0.009) and location in the posterior circulation were significantly associated with higher complications. All 3 patients who had coil extraction experienced a postoperative stroke. Aneurysm size (OR 1.2, 95% CI 1.02-1.45; p = 0.025) and higher number of interventions prior to clipping (OR 5.3, 95% CI 1.3-21.4; p = 0.019) were significant predictors of poor outcome. An aneurysm size > 7 mm was a significant predictor of incomplete obliteration and retreatment (p = 0.018). CONCLUSIONS Surgical clipping is safe and effective in treating recurrent, previously coiled cerebral aneurysms. Aneurysm size, location, and number of previous coiling procedures are important factors to consider in the management of these aneurysms. PMID- 26894463 TI - Interpretation of the causes of instability of flash visual evoked potentials in intraoperative monitoring and proposal of a recording method for reliable functional monitoring of visual evoked potentials using a light-emitting device. AB - OBJECTIVE Effective monitoring and application of visual evoked potentials (VEPs) during neurosurgery is a major challenge. While many monitoring methods have been effectively used, the use of VEPs as an objective determination method has not been established. The purpose of this report was to present a method for overcoming this limitation according to the use of a specific stimulus. METHODS Data analysis was performed in 26 cases of brain surgery. Observation was carried out for 2 groups of responses: the response derived from the start of light emission, described as the on response, and the response derived from the end of light emission, described as the off response. These reactions were separated by extending the light emission time. The waves from the visual cortex were selected from each reaction following the start and the end of light emission with consideration for the characteristics of the potential distribution. The waves were observed to characterize changes resulting from variations in duration and quantity of light emission. The results of the analysis were used to determine the optimal emission time and amount of light for effective use of wave components during VEP monitoring. RESULTS Stable and recordable waves were observed by monitoring the off response, consisting of the P1-N1-P2 component, with a wave latency of approximately 100 msec. Since the off response was correlated with the input, the stable wave derived from the off response could be adjusted by changing the light emission time and intensity. Individual differences in the latency of the off response were decreased by extending the light emission time and reducing the quantity of light. However, it was difficult to achieve stability by adjusting the light intensity and emission time using the on response. The off response was confirmed to be sufficiently stable for intraoperative monitoring. Moreover, during 1 case in which manipulation of the optic nerve was necessary, reduction in the off response was found to occur when the nerve was manipulated and to reverse when the manipulation stopped. CONCLUSIONS The off response was shown to have the capacity to function as a monitoring tool, providing more stable wave forms than the on response. Recording conditions could be adjusted to achieve a light-emitting time of 500 msec and a light quantity of 8000 Lx. Stable monitoring of VEPs using light-emitting stimuli can contribute toward improving surgical outcomes. PMID- 26894464 TI - Iatrogenic atrial septal defect following transseptal cardiac interventions. AB - In the Era of expanding use of transseptal structural heart disease interventions and catheter ablation techniques for atrial fibrillation, there is increasing interest in the iatrogenic atrial septal defect (iASD) often associated with these procedures. The purpose of this review is to summarize the current evidence on the incidence and clinical impact of iASD, to identify possible predictors of persistent iASD, and to propose a standardized method for the detection, follow up and management of iASD. PMID- 26894465 TI - Next generation sequencing of the NOTCH3 gene in a cohort of pulmonary hypertension patients. PMID- 26894466 TI - Incessant accelerated idioventricular rhythm in pregnancy: An unusual long lasting case. PMID- 26894467 TI - Real-world cost effectiveness of MitraClip combined with Medical Therapy Versus Medical therapy alone in patients with moderate or severe mitral regurgitation. AB - BACKGROUND: We evaluated the real-world cost-effectiveness of the MitraClip system (Abbott Vascular Inc., Menlo Park, CA) plus medical therapy for patients with moderate/severe mitral regurgitation, as compared with medical therapy (MT) alone. METHODS: Clinical records of patients with moderate to severe functional mitral regurgitation treated with MitraClip (N=232) or with MT (N=151) were collected and outcome analyzed with propensity score adjustment to reduce selection bias. Twelve-month outcomes were modeled over a lifetime horizon to conduct a cost-effectiveness analysis, in the payer's perspective. Costs and benefits were discounted at an annual rate of 3.5%. RESULTS: After propensity score adjustment, the average treatment effect was -9.5% probability of dying at 12months and, following lifetime modeling, 3.35+/-0.75 incremental life years and 3.01+/-0.57 incremental quality-adjusted life years. MitraClip contributed to a higher decrease in re-hospitalizations at 12months (difference=-0.54+/-0.08) and generated a more likely improvement in the New York Heart Association (NYHA) class at 12months versus NYHA at enrollment. Incremental costs, adapted to five possible scenarios, ranged from 14,493 to 29,795 ? contributing to an incremental cost-effectiveness ratio ranging from 4796 to 7908 ?. CONCLUSIONS: Compared to MT alone and given conventional threshold values, MitraClip can be considered a cost effective procedure. The cost-effectiveness of MitraClip is in line or superior to the one of other non-pharmaceutical strategies for heart failure. PMID- 26894469 TI - Novel biomarkers and therapies in cardiorenal syndrome. AB - Renal and cardiac diseases frequently co-exist and are associated with adverse outcomes. The clinical management of patients with a cardiorenal syndrome aims at reducing fluid overload and congestion, while improving kidney function. Early diagnosis and prompt therapies are key to better outcome. Biomarkers may help to gain insight on the ongoing pathological processes and since an accurate and early diagnosis of the cardiorenal syndrome based on clinical findings is not always possible. Serum creatinine, the derived eGFR and blood urea nitrogen are the standard tools for recognizing changes in renal function but suffer some limitations. In this review we will discuss the role of emerging biomarkers of renal tubular and glomerular injury, bone-mineral axis, or tubular cell-cycle arrest. PMID- 26894470 TI - Deviations from Electroneutrality in Membrane Barrier Layers: A Possible Mechanism Underlying High Salt Rejections. AB - Reverse osmosis and nanofiltration (NF) employ composite membranes whose ultrathin barrier layers are significantly more permeable to water than to salts. Although solution-diffusion models of salt transport through barrier layers typically assume ubiquitous electroneutrality, in the case of ultrathin selective skins and low ion partition coefficients, space-charge regions may occupy a significant fraction of the membrane barrier layer. This work investigates the implications of these deviations from electroneutrality on salt transport. Both immobile external surface charge and unequal cation and anion solvation energies in the barrier layer lead to regions with excess mobile charge, and the size of these regions increases with decreasing values of either feed concentrations or ion partition coefficients. Moreover, the low concentration of the more excluded ion in the space-charge region can greatly increase resistance to salt transport to enhance salt rejection during NF. These effects are especially pronounced for membranes with a fixed external surface charge density whose sign is the same as that of the more excluded ion in a salt. Because of the space-charge regions, the barrier-layer resistance to salt transport initially rises rapidly with increasing barrier thickness and then plateaus or even declines within a certain thickness range. This trend in resistance implies that thin, defect-free barrier layers will exhibit higher salt rejections than thicker layers during NF at a fixed transmembrane pressure. Deviations from electroneutrality are consistent with both changes in NF salt rejections that occur upon changing the sign of the membrane fixed external surface charge, and CaCl2 rejections that in some cases may first decrease, then increase and then decrease again with increasing CaCl2 concentrations in NF feed solutions. PMID- 26894468 TI - Mitochondrial redox status as a target for cardiovascular disease. AB - Mitochondria are major players in cellular energetics, oxidative stress and programmed cell death. Mitochondrial dynamics regulate and integrate these functions. Mitochondrial dysfunction is involved in cardiac hypertrophy, hypertension and myocardial ischemia/reperfusion injury. Reactive oxygen species generation is modulated by the fusion-fission pathway as well as key proteins such as sirtuins that act as metabolic sensors of cellular energetics. Mitochondrial redox status has thus become a good target for therapy against cardiovascular diseases. Recently, there is an influx of studies garnered towards assessing the beneficial effects of mitochondrial targeted antioxidants, drugs modulating the fusion-fission proteins, sirtuins, and other mitochondrial processes as potential cardio-protecting agents. PMID- 26894471 TI - Discrete {Ni40} Coordination Cage: A Calixarene-Based Johnson-Type (J17) Hexadecahedron. AB - We report a Johnson hexadecahedronal coordination cage, constructed via 10 Ni4-p tert-butylthiacalix[4]arene (Ni4-TC4A) units as vertices and 16 5-(pyridin-4 yl)isophthalate (PIP) ligands as tiles. It features a gyroelongated square bipyramidal geometry, equivalent to two square pyramids pillared by a square antiprism, a J17 Johnson solid. Remarkably, the cage compound exhibits a much higher uptake capacity of C3H8 than CH4, representing a promising material for separation of these two gases. In contrast, Co4-TC4A units are linked by PIP ligands and rare {Co4O4Cl2} clusters, providing a one-dimensional bamboo stick like polymer. PMID- 26894472 TI - Selective cell adhesion on femtosecond laser-microstructured polydimethylsiloxane. AB - We show that femtosecond laser irradiation of polydimethylsiloxane (PDMS) enables selective and patterned cell growth by altering the wetting properties of the surface associated with chemical and/or topographical changes. In the low pulse energy regime, the surface becomes less hydrophobic and exhibits a low water contact angle compared to the pristine material. X-ray photoelectron spectroscopy (XPS) also reveals an increased oxygen content in the irradiated regions, to which the C2C12 cells and rabbit anti-mouse protein were found to attach preferentially. In the high pulse energy regime, the laser-modified regions exhibit superhydrophobicity and were found to inhibit cell adhesion, whereas cells were found to attach to the surrounding regions due to the presence of nanoscale debris generated by the ablation process. PMID- 26894473 TI - Homozygous familial hypercholesterolemia in childhood: Genotype-phenotype description, established therapies and perspectives. AB - Familial hypercholesterolemia (FH) is a co-dominantly inherited disorder of plasma lipoprotein metabolism. The prevalence of heterozygous FH (HeFH) is between 1/500 and 1/200 whereas that of homozygous form (HoFH) is about 1/1,000,000. Diagnosis is based on cutaneous xanthomas and untreated levels of LDL-cholesterol over 500 mg/dl before 10 years of age. Life expectancy, without treatment, does not exceed 20 years of age. The aim of this study is to characterise in details a cohort of 8 HoFH paediatric patients in order to illustrate all the current therapeutic options and to add some clinical and genetic information about this rare disease. We collected demographic, clinical, biological, imaging and genotype details. Furthermore, clinical and biochemical response to different treatment methods was retrospectively evaluated. All patients had genetically proven HoFH. All patients were subject to a lipid lowering diet and medical treatment (except one), three patients underwent a liver transplant and one an hepatocytes infusion. Medical treatment was well tolerated with a median reduction of 44% and 47% in LDL-Cholesterol and Total Cholesterol respectively. The hepatocytes transplant produced a further, though slight, decrease in cholesterol levels as opposed to medical therapy alone. Transplanted patients normalized their cholesterol levels. Since the very high cardiovascular risk, HoFH requires immediate diagnosis, treatment and monitoring. Nowadays, the use of statins remains the cornerstone of medical therapy and liver transplantation is the possibly curative therapy. Besides, high hopes are pinned in new drugs (antibody targeting PCSK9, Mipomersen and Lomitapide) and stem cells. PMID- 26894474 TI - Selecting the column configuration with lowest media replacement cost for small adsorption systems. AB - A framework was developed for preliminary evaluation of the relative media replacement costs of three alternative column configurations used for adsorption systems with two vessels, such as those serving small systems. The media replacement cost is the cost of fresh media and the replacement service cost (including transportation, labor, and other non-material costs). Cost normalization methods were developed in part based on the data from US EPA Arsenic Treatment Technology Demonstration Program. Adsorption equilibrium and kinetics were modeled using the PSDM model and breakthrough curves were normalized using the target effluent to influent concentration ratio (C/Co) and the mass transfer zone fraction (%MTZBT). Two factors were found to be important for the relative replacement cost of each configuration - the frequency which at least one column needed replacement of media, and the cycle replacement cost (CRCost) which is a combination of the fresh media cost and the replacement service cost. The lead-lag configuration has the lowest annual replacement cost at low target C/Co, high %MTZBT, and high CRCost ratios. The parallel configuration performs better at high target C/Co, high %MTZBT, and high CRCost ratios. Although the single configuration (two columns operated in tandem and replaced simultaneously) has higher media consumption compared to lead-lag and parallel, it can result in the lowest replacement cost at short %MTZBT and very low CRCost ratios due to savings in the replacement service cost. PMID- 26894476 TI - Convex accelerated maximum entropy reconstruction. AB - Maximum entropy (MaxEnt) spectral reconstruction methods provide a powerful framework for spectral estimation of nonuniformly sampled datasets. Many methods exist within this framework, usually defined based on the magnitude of a Lagrange multiplier in the MaxEnt objective function. An algorithm is presented here that utilizes accelerated first-order convex optimization techniques to rapidly and reliably reconstruct nonuniformly sampled NMR datasets using the principle of maximum entropy. This algorithm - called CAMERA for Convex Accelerated Maximum Entropy Reconstruction Algorithm - is a new approach to spectral reconstruction that exhibits fast, tunable convergence in both constant-aim and constant-lambda modes. A high-performance, open source NMR data processing tool is described that implements CAMERA, and brief comparisons to existing reconstruction methods are made on several example spectra. PMID- 26894477 TI - Improvement of the Off-Resonance Saturation, an MRI sequence for positive contrast with SPM particles: Theoretical and experimental study. AB - The SuperParaMagnetic particles (SPM particles) are used as contrast agents in MRI and produce negative contrast with conventional T2 or T2(*)-weighted sequences. Unfortunately, the SPM particle detection on images acquired with such sequences is sometimes difficult because negative contrast can be created by artifacts such as air bubbles or calcification. To overcome this problem, new sequences as Off-Resonance Saturation (ORS) were developed to produce positive contrast with SPM particles. This work explores a new way to optimize the contrast generated by the ORS sequence by increasing the number of saturation pulses applied before the imaging sequence. This modified sequence is studied with numerical simulations and experiments on agarose gel phantoms. A theoretical model able to predict the contrast for different values of the sequence parameters is also developed. The results show that the contrast increases with the saturation pulses number with an optimal value of three saturation pulses in order to avoid artifacts and limit the Specific Absorption Rate (SAR) effect. The dependence of the contrast on the SPM particle concentration and sequence parameters is comparable to what was observed for the ORS sequence. PMID- 26894475 TI - Impact of persulfate and ultraviolet light activated persulfate pre-oxidation on the formation of trihalomethanes, haloacetonitriles and halonitromethanes from the chlor(am)ination of three antibiotic chloramphenicols. AB - Persulfate oxidation processes, with and without activation using ultraviolet light (respectively UV/PS and PS) have the potential to degrade anthropogenic chemicals in water. However, little is known about the impact of PS or UV/PS pre oxidation on downstream formation of disinfection by-products (DBPs). In this study the three antibiotic chloramphenicols (chloramphenicol and two of its analogues [thiamphenicol and florfenicol], referred to collectively as CAPs), which frequently occur in wastewater-impacted source waters used by drinking water treatment plants, were selected as model antibiotic compounds. The formation of carbonaceous and nitrogenous disinfection by-products, including halomethanes, haloacetonitriles and halonitromethanes, during chlorination and chloramination preceded by PS and UV/PS was investigated. No significant concentrations of haloacetonitriles and halonitromethanes were detected during chlorination. During chloramination chloramphenicol formed a considerable amount of dichloronitromethane (e.g., 3.44 +/- 0.33% mol/mol at NH2Cl dose = 1 mM) and trichloronitromethane (e.g., 0.79 +/- 0.07% mol/mol at NH2Cl dose = 1 mM), compared with THM and HAN formation. PS pre-oxidation achieved a statistically significant reduction in trichloromethane formation from chlorination, and in HAN and HNM formation from chloramination. Although UV/PS slightly increased dichloroacetonitrile formation during chloramination, it significantly decreased dichloronitromethane and trichloronitromethane formation during chloramination. Overall, the use of PS and UV/PS has the potential to have contrasting impacts on DBP formation in heavily wastewater-impacted waters, depending on the disinfection method. Hence, their application needs to be carefully balanced against the downstream effect on DBP formation. PMID- 26894478 TI - [Organ Manifestation and Subjective Sleep Quality in Sarcoidosis]. AB - BACKGROUND: Sleep disturbances are more common among sarcoidosis patients than in the general population. The influence of organ involvement on the subjective sleep quality was investigated in a large group of sarcoidosis patients. METHODS: In collaboration with the German Sarcoidosis Association, 1197 sarcoidosis patients were examined with a specially developed questionnaire with the Pittsburgh sleep quality index (PSQI) integrated into it. RESULTS: 91 % had pulmonary involvement, 65 % extra-pulmonary sarcoidosis. In 61 %, two or more organs were involved. Subjective sleep quality in PSQI declined significantly (p < 0.001) with the increase in the number of organs involved; there was a significant increase in the prevalence of known sleep apnea (p < 0.005), restless legs syndrome (RLS), percentage of women and comorbidities (all p < 0.001). In at least 33 % of patients with bone, muscle, nerve, kidney or heart involvement, the PSQI scores were > 10. CONCLUSIONS: In sarcoidosis patients with involvement of at least 2 organs, sleeping behaviour that includes RLS and sleep apnea should be evaluated. PMID- 26894479 TI - [Treatment of Cystic Fibrosis with CFTR Modulators]. AB - Personalized medicine promises that medical decisions, practices and products are tailored to the individual patient. Cystic fibrosis, an inherited disorder of chloride and bicarbonate transport in exocrine glands, is the first successful example of customized drug development for mutation-specific therapy. There are two classes of CFTR modulators: potentiators that increase the activity of CFTR at the cell surface, and correctors that either promote the read-through of nonsense mutations or facilitate the translation, folding, maturation and trafficking of mutant CFTR to the cell surface. The potentiator ivacaftor and the corrector lumacaftor are approved in Germany for the treatment of people with cystic fibrosis who carry a gating mutation such as p.Gly551Asp or who are homozygous for the most common mutation p.Phe508del, respectively. This report provides an overview of the basic defect in cystic fibrosis, the population genetics of CFTR mutations in Germany and the bioassays to assess CFTR function in humans together with the major achievements of preclinical research and clinical trials to bring CFTR modulators to the clinic. Some practical information on the use of ivacaftor and lumacaftor in daily practice and an update on pitfalls, challenges and novel strategies of bench-to-bedside development of CFTR modulators are also provided. PMID- 26894480 TI - Monitoring of extracellular pH in young dental biofilms grown in vivo in the presence and absence of sucrose. AB - BACKGROUND AND OBJECTIVE: pH in dental biofilms is of central importance for the development of caries. We used the ratiometric pH-sensitive dye C-SNARF-4 in combination with digital image analysis to monitor extracellular pH in dental biofilms grown in situ with and without sucrose supply. DESIGN: Dental biofilms (48 h) from 10 individuals were collected on glass slabs mounted on intra-oral appliances. During growth, appliances were immersed extra-orally in either physiological saline or 4% sucrose for 2 min, eight times per day. Fluorescence emissions of C-SNARF-4 in deep layers of the biofilms were recorded ex vivo with confocal microscopy for 15 min or for 1 h after exposure to 0.4% glucose. Extracellular pH was determined ratiometrically using digital image analysis. RESULTS: Extracellular pH dropped rapidly in most examined sites after addition of glucose. Distinct pH microenvironments were observed within single biofilms. The variation in pH was similar between sites within the same biofilm and sites from different individuals. pH drop patterns did not differ between biofilms exposed to sucrose-free and sucrose-rich environments. CONCLUSION: The present study is the first of its kind to apply the combination of pH ratiometry and digital image analysis to systematically record extracellular pH in intact dental biofilms from several individuals for up to 1 h. We observed highly heterogeneous pH landscapes and the presence of acidogenic microenvironments - 'acidogenic hotspots' - within the biofilms. The data suggest that pH drops in young (48 h) dental biofilms are independent of the sucrose supply during growth. PMID- 26894481 TI - Phosphine Oxide-Sc(OTf)3 Catalyzed Highly Regio- and Enantioselective Bromoaminocyclization of (E)-Cinnamyl Tosylcarbamates. An Approach to a Class of Synthetically Versatile Functionalized Molecules. AB - A highly regio- and enantioselective bromoaminocyclization of (E)-cinnamyl tosylcarbamates catalyzed by a chiral phosphine oxide-Sc(OTf)3 complex is described. A wide variety of optically active aryl 5-bromo-1,3-oxazinan-2-ones can be obtained with high yield and enantioselectivity. PMID- 26894482 TI - Psychological distress leads to reduced physical activity and fitness in children: the Australian longitudinal LOOK study. AB - Stress and depression can affect an individual's level of physical activity and fitness, which may place them at risk of developing cardiovascular disease. This study investigates the longitudinal effects of stress and depression on physical activity and cardiorespiratory fitness among youth. Six hundred and seventy-six children, initially aged 8 years, from the LOOK study completed a modified version of the Children's Depression Inventory, the Children's Stress Questionnaire, and objective physical activity and cardiorespiratory fitness assessments on three occasions, every 4 years. Depressive symptoms had a direct effect (longitudinal) on the cardiorespiratory fitness of girls, with a similar trend for boys. In cross-sectional analyses, a child who identified with more symptoms of depression and stress was likely to be less fit and less physically active, which in girls extended to less moderate-to-vigorous physical activity. Our findings, that both physical activity and fitness are impacted by depression and stress may contribute to strategies directed towards achieving enhanced physical activity and reductions in obesity. PMID- 26894483 TI - Brain serotonin 4 receptor binding is associated with the cortisol awakening response. AB - Serotonin signalling is considered critical for an appropriate and dynamic adaptation to stress. Previously, we have shown that prefrontal serotonin transporter (SERT) binding is positively associated with the cortisol awakening response (CAR) (Frokjaer et al., 2013), which is an index of hypothalamic pituitary-adrenal (HPA)-axis output dynamics. Here, we investigated in healthy individuals if cerebral serotonin 4 receptor (5-HT4r) binding, reported to be a proxy for serotonin levels, is associated with CAR. Thirty healthy volunteers (25 males, age range 20-56 years) underwent 5-HT4r PET imaging with [(11)C]-SB207145, genotyping of the SERT-linked polymorphic region (5-HTTLPR), and performed serial home sampling of saliva (5 time points from 0 to 60min from awakening) to assess CAR. The association between 5-HT4r binding in 4 regions of interest (prefrontal cortex, anterior cingulate cortex, pallidostriatum, and hippocampus) and CAR was tested using multiple linear regression with adjustment for age and 5-HTTLPR genotype. Finally, an exploratory voxel-based analysis of the association was performed. CAR was negatively associated with 5-HT4r binding in pallidostriatum (p=0.01), prefrontal cortex (p=0.03), and anterior cingulate cortex (p=0.002), respectively, but showed no association in hippocampus. The results remained significant when taking into account other potentially relevant covariates. In conclusion, our finding reinforces an association between HPA-axis function and serotonin signaling in vivo in humans. We suggest that higher synaptic serotonin concentration, here indexed by lower 5-HT4r binding, supports HPA-axis dynamics, which in healthy volunteers is reflected by a robust CAR. PMID- 26894484 TI - PTSD is associated with an increase in aged T cell phenotypes in adults living in Detroit. AB - BACKGROUND: Psychosocial stress is thought to play a key role in the acceleration of immunological aging. This study investigated the relationship between lifetime and past-year history of post-traumatic stress disorder (PTSD) and the distribution of T cell phenotypes thought to be characteristic of immunological aging. METHODS: Data were from 85 individuals who participated in the community based Detroit Neighborhood Health Study. Immune markers assessed included the CD4:CD8 ratio, the ratio of late-differentiated effector (CCR7-CD45RA+CD27-CD28-) to naive (CCR7+CD45RA+CD27+CD28+) T cells, the percentage of KLRG1-expressing cells, and the percentage of CD57-expressing cells. RESULTS: In models adjusted for age, gender, race/ethnicity, education, smoking status, and medication use, we found that past-year PTSD was associated with statistically significant differences in the CD8+ T cell population, including a higher ratio of late differentiated effector to naive T cells, a higher percentage of KLRG1+ cells, and a higher percentage of CD57+ cells. The percentage of CD57+ cells in the CD4 subset was also significantly higher and the CD4:CD8 ratio significantly lower among individuals who had experienced past-year PTSD. Lifetime PTSD was also associated with differences in several parameters of immune aging. CONCLUSIONS: PTSD is associated with an aged immune phenotype and should be evaluated as a potential catalyzer of accelerated immunological aging in future studies. PMID- 26894485 TI - Randomized phase II study of loratadine for the prevention of bone pain caused by pegfilgrastim. AB - PURPOSE: Bone pain is a common side effect of pegfilgrastim and can interfere with quality of life and treatment adherence. This study investigated the impact of antihistamine prophylaxis on pegfilgrastim-induced bone pain. METHODS: This is a two-stage enrichment trial design. Patients receiving an initial dose of pegfilgrastim after chemotherapy were enrolled into the observation (OBS) stage. Those who developed significant back or leg bone pain (SP) were enrolled into the treatment (TRT) stage and randomized to daily loratadine 10 mg or placebo for 7 days. SP was defined by Brief Pain Inventory as back or leg pain score >=5 and a 2-point increase after pegfilgrastim. The primary end point of TRT was reduction of worst back or leg bone pain with loratadine, defined as a 2-point decrease after treatment compared to OBS. RESULTS: Two hundred thirteen patients were included in the final analysis. Incidence of SP was 30.5 %. The SP subset had a worse overall Functional Assessment of Cancer Therapy-Bone Pain score (33.9 vs. 51.7, p < 0.001) and a higher mean white blood cell count (15.4 vs. 8.4 K/cm(3), p = 0.013) following pegfilgrastim than those without SP. Forty-six patients were randomized in the TRT. Benefit was 77.3 % with loratadine and 62.5 % with placebo (p = 0.35). Baseline NSAID use was documented in four patients (18.2 %) in loratadine arm and two patients (8.3 %) in placebo arm, with baseline non-NSAID use documented in five (22.7 %) and six (25 %) patients, respectively. Eight additional patients used NSAIDS by day 8 compared to day 1 (six in the loratadine and two in the placebo arm). A total of six additional patients used non-NSAIDS by day 8 compared to day 1 (four in the loratadine and two in the placebo arm). CONCLUSIONS: Administration of prophylactic loratadine does not decrease the incidence of severe bone pain or improve quality of life in a high-risk patient population. ClinicalTrials.gov identifier: NCT01311336. PMID- 26894486 TI - Current and (Potential) Future Effects of the Affordable Care Act on HIV Prevention. AB - Recent advances in science, program, and policy could better position the nation to achieve its vision of the USA as a place where new HIV infections are rare. Among these developments, passage of the Patient Protection and Affordable Care Act (ACA) in 2010 may prove particularly important, as the health system transformations it has launched offer a supportive foundation for realizing the potential of other advances, both within and beyond the clinical arena. This article summarizes opportunities to expand access to high-impact HIV prevention interventions under the ACA, examines whether available evidence indicates that these opportunities are being realized, and considers potential challenges to further gains for HIV prevention in an era of health reform. This article also highlights the new roles that HIV prevention programs and providers may assume in a health system no longer defined by fragmentation among public health, medical care, and community service providers. PMID- 26894488 TI - Long-Term Efficacy of Laparoscopic or Robotic Adenomyomectomy with or without Medical Treatment for Severely Symptomatic Adenomyosis. AB - BACKGROUND/AIMS: To determine the long-term efficacy of laparoscopic or robotic adenomyomectomy with or without gonadotropin-releasing hormone (GnRH) for the treatment of severely symptomatic adenomyosis. METHODS: Between August 2008 and May 2011, we prospectively observed 33 patients who underwent laparoscopic or robotic adenomyomectomy with uterine artery ligation for the treatment of symptomatic adenomyosis. Seventeen patients (52%) received 3-course GnRH agonist treatment after the adenomyomectomy. RESULTS: The mean operating time was 147.4 +/- 52.0 min, and the mean blood loss was 36.1 +/- 37.4 ml. Postoperative complications occurred in 5 patients, including 4 cases of febrile morbidity, 1 case of ileus and 1 case of pelvic abscess. Patients had statistically significant symptom relief during the 3-year follow-up period. Four of the 33 patients (12%) showed symptom relapse; 3 patients showed a relapse with dysmenorrhea and 1 patient showed a relapse with menorrhagia. There were no significant differences in terms of therapeutic outcomes between surgical-only and surgical-medical treatment. CONCLUSION: Laparoscopic or robotic adenomyomectomy was feasible and safe for women with severely symptomatic adenomyosis who requested uterine preservation. Moreover, this procedure provided long-term symptom control, regardless of postoperative GnRH agonist administration. PMID- 26894487 TI - Cascade of Refusal-What Does It Mean for the Future of Treatment as Prevention in Sub-Saharan Africa? AB - Recent recommendations by the World Health Organization support treatment for all people living with HIV (PLWH) globally to be initiated at the point of testing. While there has been marked success in efforts to identify and expand treatment for PLWH throughout sub-Saharan Africa, the goal of universal treatment may prove challenging to achieve. The pre-ART phase of the care cascade from HIV testing to HIV treatment initiation includes several social and structural barriers. One such barrier is antiretroviral therapy (ART) treatment refusal, a phenomenon in which HIV-infected individuals choose not to start treatment upon learning their ART eligibility. Our goal is to provide further understanding of why treatment eligible adults may choose to present for HIV testing but not initiate ART when indicated. In this article, we will discuss factors driving pre-ART loss and present a framework for understanding the impact of decision-making on early losses in the care cascade, with a focus on ART refusal. PMID- 26894489 TI - Judkins right guiding catheter bailed out acute aortic insufficiency during balloon aortic valvuloplasty. AB - The introduction of transcatheter aortic valve implantation focuses attention on balloon aortic valvuloplasty (BAV) once again. BAV is effective for several clinical conditions, but fatal complications including acute severe aortic insufficiency may occur, although rare. We report a case of acute aortic insufficiency occurring during BAV, which was bailed out remarkably by the catheter method. When acute aortic insufficiency occurs during BAV, this simple and effective procedure should be attempted before conversion to emergency surgery. PMID- 26894490 TI - Diagnosis of Lynch syndrome before colorectal resection: does it matter? PMID- 26894492 TI - Genotoxicity Effects in Freshwater Fish from a Brazilian Impacted River. AB - This study evaluated the incidence of nuclear abnormalities (NA) in four fish species from an impacted river in Northeastern Brazil, characterized by accumulation of heavy metals and organic sewage. Two carnivores (Serrasalmus brandtii and Hoplias malabaricus) and two omnivore species (Oreochromis niloticus and Geophagus brasiliensis), used as food sources by local populations, were collected during the dry and the rainy season along Contas River basin. Nuclear abnormalities (bulbs, binuclei, lobes, micronuclei, notches, and vacuoles) were reported in all fish samples, with high occurrence in S. brandtii and H. malabaricus, species commonly found in local fish markets. This result agrees with previous analyses of accumulation of trace metals in both species, suggesting an association of genotoxic effects and biomagnification. Moreover, native specimens collected near urban areas presented higher frequencies of NA while O. niloticus seems to be more tolerant to environmental contamination. Therefore, effective policies are required to reduce the contamination of Contas River, since pollution by xenobiotics are potential threats to both local biodiversity and human population. PMID- 26894491 TI - Regulation of DJ-1 by Glutaredoxin 1 in Vivo: Implications for Parkinson's Disease. AB - Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide, caused by the degeneration of the dopaminergic neurons in the substantia nigra. Mutations in PARK7 (DJ-1) result in early onset autosomal recessive PD, and oxidative modification of DJ-1 has been reported to regulate the protective activity of DJ-1 in vitro. Glutathionylation is a prevalent redox modification of proteins resulting from the disulfide adduction of the glutathione moiety to a reactive cysteine-SH, and glutathionylation of specific proteins has been implicated in regulation of cell viability. Glutaredoxin 1 (Grx1) is the principal deglutathionylating enzyme within cells, and it has been reported to mediate protection of dopaminergic neurons in Caenorhabditis elegans; however many of the functional downstream targets of Grx1 in vivo remain unknown. Previously, DJ-1 protein content was shown to decrease concomitantly with diminution of Grx1 protein content in cell culture of model neurons (SH-SY5Y and Neuro-2A lines). In the current study we aimed to investigate the regulation of DJ-1 by Grx1 in vivo and characterize its glutathionylation in vitro. Here, with Grx(-/-) mice we provide show that Grx1 regulates protein levels of DJ-1 in vivo. Furthermore, with model neuronal cells (SH-SY5Y) we observed decreased DJ-1 protein content in response to treatment with known glutathionylating agents, and with isolated DJ-1 we identified two distinct sites of glutathionylation. Finally, we found that overexpression of DJ-1 in the dopaminergic neurons partly compensates for the loss of the Grx1 homologue in a C. elegans in vivo model of PD. Therefore, our results reveal a novel redox modification of DJ-1 and suggest a novel regulatory mechanism for DJ-1 content in vivo. PMID- 26894493 TI - Assessment of Heavy Metal Accumulation in the Golden Jackal (Canis aureus) as a Possible Bioindicator in an Agricultural Environment in Bulgaria. AB - The aim of this study was to evaluate the residues of heavy metals as an indicator of environmental pollution in internal organs of golden jackal (Canis aureus) from an agricultural region in Bulgaria. It was demonstrated that the golden jackal has high potential for specific accumulation of heavy metals, thus implying that this species may serve as a biological indicator of their presence in the agricultural regions, which it inhabits. The concentrations of the targeted elements (mean [mg/kg of dried tissue] +/- SD) were respectively: Cu 57.62 +/- 10.76; Zn-141.45 +/- 11.33; Ni-0.28 +/- 0.19; Co-0.46 +/- 0.30; Pb-6.88 +/- 1.67 and Cd-0.58 +/- 0.16 in liver and Cu-17.67 +/- 5.01; Zn-58.28 +/- 10.81; Ni-0.51 +/- 0.4; Co-0.52 +/- 0.29; Pb-4.03 +/- 1.32 and Cd-1.41 +/- 0.22 in kidney samples. The concentrations we found revealed the specific accumulation of these metals in golden jackal and provide values, within which negative effects on the advancement of its populations should not be expected. PMID- 26894494 TI - Scapular muscle activity in a variety of plyometric exercises. AB - BACKGROUND: Plyometric shoulder exercises are commonly used to progress from slow analytical strength training to more demanding high speed power training in the return to play phase after shoulder injury. The aim of this study was first, to investigate scapular muscle activity in plyometric exercises to support exercise selection in practice and second, to enhance understanding of how scapular muscles are recruited during the back and forth movement phase of these exercises. METHODS: Thirty-two healthy subjects performed 10 plyometric exercises while surface EMG-activity of the scapular muscles (upper (UT), middle (MT) and lower trapezius (LT) and serratus anterior (SA)) was registered. A high speed camera tracked start and end of the back and forth movement. RESULTS: Mean scapular EMG activity during the 10 exercises ranged from 14.50% to 76.26%MVC for UT, from 15.19% to 96.55%MVC for MT, from 13.18% to 94.35%MVC for LT and from 13.50% to 98.50%MVC for SA. Anova for repeated measures showed significant differences in scapular muscle activity between exercises (p<0.001) and between the back and forth movement (p<0.001) within exercises. CONCLUSION: Plyometric shoulder exercises require moderate (31-60%MVC) to high (>60%MVC) scapular muscle activity. Highest MT/LT activity was present in prone plyometric external rotation and flexion. Highest SA activity was found in plyometric external rotation and flexion with Xco and plyometric push up on Bosu. Specific exercises can be selected that recruit minimal levels of UT activity (<15%): side lying plyometric external rotation and horizontal abduction or plyometric push up on the Bosu. The results of this study support exercise selection for clinical practice. PMID- 26894495 TI - A phase I/IIa clinical trial in stage IV melanoma of an autologous tumor dendritic cell fusion (dendritoma) vaccine with low dose interleukin-2. AB - BACKGROUND: Stage IV melanoma has high mortality, largely unaffected by traditional therapies. Immunotherapy including cytokine therapies and checkpoint inhibitors improves outcomes, but has significant toxicities. In this phase I/IIa trial, we investigated safety and efficacy of a dendritoma vaccine, an active, specific immunotherapy, in stage IV melanoma patients. METHODS: Autologous tumor lysate and dendritic cells were fused creating dendritoma vaccines for each patient. Phase I patients were vaccinated every 3 months with IL-2 given for 5 days after initial inoculation. Phase IIa patients were vaccinated every 6 weeks with IL-2 given on days 1, 3 and 5 after initial inoculation. Toxicity and clinical outcomes were assessed. RESULTS: Twenty-five patients were enrolled and inoculated. All dendritoma and IL-2 toxicities were =3 versus <3 inoculations (43.1 vs. 16.7 %, p = 0.02) was observed. Patients with no evidence of disease (NED) showed improved OS (80 vs. 14 %, p = 0.005). No clinicopathologic differences were present between phase I (n = 10) and IIa (n = 15) patients; phase IIa patients received more frequent dosing and higher mean number of inoculations. Phase IIa median OS was significantly higher (23.8 vs. 8.7 months, p = 0.004). CONCLUSIONS: The dendritoma vaccine has minimal toxicity profile with potential clinical benefit. There was OS advantage for NED stage IV patients, those receiving higher number of doses and increased frequency. Based on these results, we initiated a phase IIb trial utilizing improved dendritoma technology in the adjuvant setting for NED stage III/IV melanoma patients. PMID- 26894496 TI - In vitro acaricidal activity of Bobgunnia madagascariensis Desv. against Amblyomma variegatum (Fabricius) (Acari: Ixodidae). AB - The objective of the study was to determine the acaricidal properties of Bobgunnia madagascariensis (Desv.) J.H. Kirkbr. and Wiersema (Leguminosae) against adult Amblyomma variegatum (Fabricius) ticks, using Tephrosia vogelii Hook.f. (Leguminosae) as a positive control. Plant extracts of both were prepared using methanol, acetone and chloroform as extraction solvents. Methanol leaf extracts of T. vogelii (0.014 g) and methanol fruit extracts of B. madagascariensis (0.0062 g) gave the highest mean extraction weights among the plant parts and solvents used. In free contact bioassays, only methanol extracts of the bark and leaf material of T. vogelii and methanol fruit extracts of B. madagascariensis produced 100 % mortality of A. variegatum ticks in 24 h. The acaricidal activity of methanol leaf extracts of T. vogelii persisted for up to 8 days while that of fruit extracts of B. madagascariensis persisted for only 6 days. In topical application bioassays, the toxicity of T. vogelii and B. madagascariensis extracts was found to be significantly different at 95 % confidence level, with B. madagascariensis extracts (LD50 0.030 w/v) being more toxic than T. vogelii extracts (LD50 0.555 w/v). This study has shown that plant extracts of B. madagascariensis and T. vogelii extracts have significant in vitro acaricidal activity against A. variegatum ticks and can thus be considered as alternatives for tick control. Further research is however required on persistence, safety and the required application rates. PMID- 26894497 TI - Effects of a long-acting trace mineral rumen bolus supplement on growth performance, metabolic profiles, and trace mineral status of growing camels. AB - A study was conducted to evaluate the effects of a long-acting trace mineral rumen bolus (TMB) supplement on the productive performance, metabolic profiles, and trace mineral status of growing camels under natural grazing conditions. Fifteen 6-month-old growing male camels (average bodyweight 139.51 +/- 26.49 kg) were used in a 150-day trial. Animals were individually housed in a shaded pen and randomly assigned to receive zero (control group, CON), one (TMB1), or two (TMB2) long-acting TMBs. Feed intake was measured weekly, and camels were weighed monthly. Blood samples were collected from all camels on days 1, 30, 60, 90, 120, and 150 to obtain metabolic profiles. Zinc, selenium, copper, cobalt, and manganese concentrations were determined in the diet, serum, and liver. In comparison with controls, giving camels one TMB increased the average daily gain (14.38%; P < 0.04) and feed efficiency (13.68%; P < 0.01). Additionally, the serum and liver concentrations of zinc, copper, selenium, cobalt, and manganese were greater (P < 0.01) in camels in the TMB2 group. These data indicate that TMB supplementation has positive effects on the growth performance and trace mineral profiles of camels. Different levels, sources, and synergistic combinations of trace minerals can be used in further studies to elucidate their abilities to increase productive variables as well as their availability and cost to the camel industry. PMID- 26894498 TI - Feed intake and growth performance of growing pigs fed on Acacia tortilis leaf meal treated with polyethylene glycol. AB - The objective of the study was to determine the response in feed intake and performance of pigs fed on incremental levels of polyethylene glycol (PEG). Forty eighty male F1 hybrid pigs were randomly allotted to six diets containing 0, 5, 10, 15, 20, and 25 g/kg of PEG, respectively. Acacia tortilis leaf meal was included at a rate of 150 g/kg. Each diet was offered ad libitum to eight pigs in individual pens. Average daily feed intake (ADFI), scaled feed intake (SFI), average daily gain (ADG), and gain to feed ratio (G:F) were determined weekly. The ADG showed a linear response to PEG (p < 0.01). The linear regression equation was y = 0.0061x + 0.6052 (R(2) = 0.64). There was a quadratic response to PEG on ADFI, and SFI (p < 0.01) and G:F (p > 0.05). The regression equations and R(2) values were as follows: ADFI y = 0.0008x(2) - 00086x + 1.2339 (R(2) = 0.96), SFI y = 0.0147x(2) - 0.2349x + 40.096 (R(2) = 0.95), and G:F ratio y = 0.0002x(2) - 0.0017x + 0.5168 (R(2) = 0.56). The ADFI, SFI, and ADG increased as weeks of feeding progressed (p < 0.01), but the G:F ratio decreased as weeks increased. It can be concluded that the relationship between PEG inclusion and performance of growing pigs fed on A. tortilis is exponential, rather than linear. The economic benefit of using PEG depend on cost of labor, availability of Acacia, costs of harvesting together with processing, and acceptability of the pork. PMID- 26894499 TI - The influence of trees on the thermal environment and behaviour of grazing heifers in Brazilian Midwest. AB - The intensification of the livestock production system has gained prominence over the last decades. In addition to the reduction of grazing areas and increased productivity per hectare, the intercropping involving forest tree species and ruminants has been established as a sustainable production model, generating income and valuation of natural capital. Besides the social, economic, and environmental aspects, the animal welfare is a noteworthy factor. The objective of this study was to evaluate the microclimatic conditions in an open-pasture and in silvopastoral systems, considering the Temperature Humidity Index (THI) and alterations in animal behavior. Three different pasture arrangements were analyzed in this study: total absence of trees in an open-pasture (ArrA), presence of peripheral trees (Eucalyptus spp.) along the border fences (ArrB), and an intensive wooded area aggregated with pasture (ArrC). A herd of 24 crossbreed heifers (3/4 and 7/8 Holstein-Girolando breed) was evaluated. Behavior data were collected every 15 min starting at 08 h00 with readings ending at 16 h00. THI was used to evaluate the environmental comfort. The THI found in the system with open-pasture and in the two systems with silvopastoral arrangement reached critical levels. The two arrangements with eucalyptus rows were not capable of eliminating heat stress in the conditions found in the north region of Mato Grosso State although better conditions were obtained under the tree canopy. The differences between the microclimatic variables for the three arrangements modified the behavior of the animals regarding their location and activity, except for water consumption. PMID- 26894500 TI - Identification of polymorphism in fatty acid binding protein 3 (FABP3) gene and its association with milk fat traits in riverine buffalo (Bubalus bubalis). AB - The fatty acid binding protein 3 (FABP3) gene, known to be associated with fat percentage of milk and meat in bovines, was screened among swamp and riverine buffaloes for polymorphism detection and further association with milk fat contents. An SNP g.307C > T was identified in the intron 2 (+53 exon 2) region of FABP3 gene of Indian buffaloes. The SNP identified was genotyped in 692 animals belonging to 15 riverine, swamp and hybrid (riverine * swamp) buffalo populations of diverse phenotypes and utilities, by PCR-RFLP. A marked contrast was observed between the C and T allele frequencies in three types of buffaloes. The frequency of C allele ranged from 0.67 to 0.96 in pure swamp buffalo populations, with the highest in Mizoram (0.96). Whereas the frequency of T allele was high across all the Indian riverine buffalo breeds, ranging from 0.57 to 0.96. None of the genotypes at FABP3 g.307C > T locus was found to have significant association with milk fat and other production traits in Mehsana dairy buffalo breed. Our study revealed marked differences in the allele frequencies between riverine and swamp buffaloes at FABP3 g.307C > T locus, without any significant association with different milk traits in riverine buffaloes. PMID- 26894501 TI - Vitamin E supplementation of undernourished ewes pre- and post-lambing reduces weight loss of ewes and increases weight of lambs. AB - The aim of this study was to test if vitamin E supplementation during late gestation and early lactation would affect the weight of ewes under nutritional restriction and the performance of their lambs. Mature Rambouillet ewes (n = 37) were fed a diet that supplied 70 % of the energy and 80 % of recommended protein requirements and randomly assigned to either vitamin E (vit E, n = 20, 4 IU of alpha-tocopherol kg(-1) of live weight) or control (n = 17, without vitamin E supplementation). During the experimental period, the mean weight of ewes decreased from 74.6 +/- 2.4 to 58.1 +/- 2.2 kg. Weight loss of ewes was slightly less for the vit E than the control (-65 vs -124 g day(-1), SEM = 46; P = 0.07). Lambs born from vit E-supplemented ewes were heavier than lambs from the control and grew significantly faster (239 vs 195 g day(-1), SEM = 29.3, P < 0.05) with heavier weights at weaning (16.5 vs 13.5 kg, SEM = 1.8, P < 0.05). Besides, birth weight, weaning weight and daily weight gain favoured to single lambs and to male lambs (P < 0.05). Weaning weight was positively correlated to birth weight (P < 0.05) and weight gain (P < 0.001). When the nutrient requirements for ewes are not met, supplementation of vitamin E during late gestation and early lactation might be an effective strategy to minimise ewe weight loss as well as to increase lamb growth. PMID- 26894502 TI - Synthesis and Biological Properties of Porphyrin-Containing Polymeric Micelles with Different Sizes. AB - To understand the size effect of polymeric micelles on their biological properties, such as cellular uptake, biodistribution, tumor accumulation, and so on, we prepared a series of doxorubicin (DOX)-loaded protoporphyrin (PP) poly(epsilon-caprolactone) (PCL)-poly(ethylene glycol) (PEG) micelles with different diameters (40, 70, 100, and 130 nm). The incorporation of the protoporphyrin moiety enhanced the stability of the micelles and provided luminescent capability that is useful in the investigation of the cellular uptake of the micelles by fluorescence imaging. The biodistributions of the micelles in mice bearing tumors were evaluated by near-infrared fluorescence imaging and DOX concentration measurements in different tissues. The in vitro and in vivo investigations demonstrated the pronounced dependence of the cellular uptake, biodistribution, and antitumor effectiveness of the micelles on their size. PMID- 26894503 TI - Effect of Resistance Training and Various Sources of Protein Supplementation on Body Fat Mass and Metabolic Profile in Sarcopenic Overweight Older Adult Men: A Pilot Study. AB - The decrease in resting energy expenditure (REE) and fat oxidation with aging is associated with an increase in fat mass (FM), and both could be prevented by exercise such as resistance training. Dairy consumption has also been shown to promote FM loss in different subpopulations and to be positively associated with fat oxidation. Therefore, we sought to determine whether resistance exercise combined with dairy supplementation could have an additive impact on FM and energy metabolism, especially in individuals with a deficit in muscle mass. Twenty-six older overweight sarcopenic men (65 +/- 5 years old) were recruited for the study. They participated in 4 months of resistance exercise and were randomized into three groups for postexercise shakes (control, dairy, and nondairy isocaloric and isoprotein supplement with 375 ml and ~280 calories per shake). Body composition was measured by dual X-ray absorptiometry and REE by indirect calorimetry. Fasting glucose, insulin, leptin, inflammatory profile, and blood lipid profile were also measured. Significant decreases were observed with FM only in the dairy supplement group; no changes were observed for any other variables. To conclude, FM may decrease without changes in metabolic parameters during resistance training and dairy supplementation with no caloric restriction without having any impact on metabolic properties. More studies are warranted to explain this significant decrease in FM. PMID- 26894504 TI - Potential Foraging Decisions by a Desert Ungulate to Balance Water and Nutrient Intake in a Water-Stressed Environment. AB - Arid climates have unpredictable precipitation patterns, and wildlife managers often provide supplemental water to help desert ungulates endure the hottest, driest periods. When surface water is unavailable, the only source of water for ungulates comes from the forage they consume, and they must make resourceful foraging decisions to meet their requirements. We compared two desert bighorn sheep (Ovis canadensis nelsoni) populations in Arizona, USA: a treatment population with supplemental water removed during treatment, and a control population. We examined whether sheep altered their seasonal diets without supplemental water. We calculated water and nutrient intake and metabolic water production from dry matter intake and forage moisture and nitrogen content, to determine whether sheep could meet their seasonal daily water and nutrient requirements solely from forage. Diets of sheep were higher in protein (all seasons) and moisture (autumn and winter) during treatment compared to pretreatment. During treatment, sheep diet composition was similar between the treatment and control populations, which suggests, under the climatic conditions of this study, water removal did not influence sheep diets. We estimated that under drought conditions, without any surface water available (although small ephemeral potholes would contain water after rains), female and male sheep would be unable to meet their daily water requirements in all seasons, except winter, when reproductive females had a nitrogen deficit. We determined that sheep could achieve water and nutrient balances in all seasons by shifting their total diet proportions by 8-55% from lower to higher moisture and nitrogen forage species. We elucidate how seasonal forage quality and foraging decisions by desert ungulates allow them to cope with their xeric and uncertain environment, and suggest that, with the forage conditions observed in our study area during this study period, providing supplemental water during water-stressed periods may not be necessary for desert bighorn sheep. PMID- 26894505 TI - Flesh-eating Streptococcus pyogenes triggers the expression of receptor activator of nuclear factor-kappaB ligand. AB - Human CD46 is a receptor for the M protein of group A streptococcus (GAS). The emm1 GAS strain GAS472 was isolated from a patient suffering from streptococcal toxic shock-like syndrome. Human CD46-expressing transgenic (Tg) mice developed necrotizing fasciitis associated with osteoclast-mediated progressive and severe bone destruction in the hind paws 3 days after subcutaneous infection with 5 * 10(5) colony-forming units of GAS472. GAS472 infection induced expression of the receptor activator of nuclear factor-kappaB ligand (RANKL) while concomitantly reducing osteoprotegerin expression in the hind limb bones of CD46 Tg mice. Micro computed tomography analysis of the bones suggested that GAS472 infection induced local bone erosion and systemic bone loss in CD46 Tg mice. Because treatment with monoclonal antibodies (mAbs) against mouse CD4(+) and CD8(+) T lymphocytes did not inhibit osteoclastogenesis, T lymphocyte-derived RANKL was not considered a major contributor to massive bone loss during GAS472 infection. However, immunohistochemical analysis of the hind limb bones showed that GAS472 infection stimulated RANKL production in various bone marrow cells, including fibroblast like cells. Treatment with a mAb against mouse RANKL significantly inhibited osteoclast formation and bone resorption. These data suggest that increased expression of RANKL in heterogeneous bone marrow cells provoked bone destruction during GAS infection. PMID- 26894506 TI - Anaplastic thyroid cancer: Prognostic factors, patterns of care, and overall survival. AB - BACKGROUND: Anaplastic thyroid cancer (ATC) represents a rare, aggressive malignancy. We analyzed factors predictive for overall survival (OS) and treatment modality utilization. METHODS: Using the National Cancer Data Base, we identified 3552 patients with ATC. Factors associated with surgery, high-dose radiotherapy (RT; >=59.4 Gy), and chemotherapy utilization were evaluated using multivariable logistic regression. From this, an inverse probability-weighted propensity score was incorporated into multivariable Cox regression analyses for OS. RESULTS: Numerous factors predictive for high-dose RT, total thyroidectomy, and chemotherapy utilization are described. Factors associated with improved survival were absence of clinical or pathologic lymph node involvement, absence of metastasis, tumor size <=6 cm, negative surgical margins, surgery, RT, and chemotherapy. On conditional landmark analysis, improved survival seen with chemotherapy and surgery other than total thyroidectomy was lost, but persisted for total thyroidectomy and high-dose RT. CONCLUSION: Even after correction for selection and immortal time bias, high-dose RT resulted in improved survival. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: E2083-E2090, 2016. PMID- 26894507 TI - Antacid Use and De Novo Brain Metastases in Patients with Epidermal Growth Factor Receptor-Mutant Non-Small Cell Lung Cancer Who Were Treated Using First-Line First-Generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors. AB - BACKGROUND: Antacid treatments decrease the serum concentrations of first generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs), although it is unknown whether antacids affect clinical outcomes. As cerebrospinal fluid concentrations of TKIs are much lower than serum concentrations, we hypothesized that this drug-drug interaction might affect the prognosis of patients with de novo brain metastases. MATERIALS AND METHODS: This retrospective study evaluated 269 patients with EGFR-mutant non-small cell lung cancer (NSCLC) who had been diagnosed between December 2010 and December 2013, and had been treated using first-line first-generation EGFR-TKIs. Among these patients, we identified patients who concurrently used H2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) as antacids. Patients who exhibited >30% overlap between the use of TKIs and antacids were considered antacid users. RESULTS: Fifty-seven patients (57/269, 21.2%) were antacid users, and antacid use did not significantly affect progression-free survival (PFS; no antacids: 11.2 months, H2RAs: 9.4 months, PPIs: 6.7 months; p = 0.234). However, antacid use significantly reduced overall survival (OS; no antacids: 25.0 months, H2RAs: 15.5 months, PPIs: 11.3 months; p = 0.002). Antacid use did not affect PFS for various metastasis sites, although antacid users with de novo brain metastases exhibited significantly shorter OS, compared to non-users (11.8 vs. 16.3 months, respectively; p = 0.041). Antacid use did not significantly affect OS in patients with bone, liver, or pleural metastases. CONCLUSION: Antacid use reduced OS among patients with EGFR-mutant NSCLC who were treated using first-line first generation EGFR-TKIs, and especially among patients with de novo brain metastases. PMID- 26894508 TI - Detection of base-pair mismatches in DNA using graphene-based nanopore device. AB - We present a unique way to detect base-pair mismatches in DNA, leading to a different epigenetic disorder by the method of nanopore sequencing. Based on a tight-binding formulation of a graphene-based nanopore device, using the Green's function approach we study the changes in the electronic transport properties of the device as we translocate a double-stranded DNA through the nanopore embedded in a zigzag graphene nanoribbon. In the present work we are not only successful in detecting the usual AT and GC pairs but also a set of possible mismatches in the complementary base pairing. PMID- 26894509 TI - Targeting fatty acid synthase with ASC-J9 suppresses proliferation and invasion of prostate cancer cells. AB - Fatty acid synthase (FASN) is the key enzyme for the control of fatty acid synthesis that contributes significantly to the prostate cancer (PCa) progression. It was reported that androgens were able to induce FASN expression in PCa, and addition of the anti-androgen Casodex might suppress the androgen induced FASN expression. However, here we found androgen-deprivation-therapy (ADT) with anti-androgens Bicalutamide (Casodex) or Enzalutamide (MDV3100) had little effect to suppress FASN expression and FASN-mediated cell growth and invasion during the castration resistant stage when the androgen concentration is 1 nM DHT (dihydrotestosterone). In contrast, the newly developed androgen receptor (AR) degradation enhancer ASC-J9(r) suppressed FASN expression and FASN mediated cell growth and invasion in various PCa cell lines at 1 nM DHT. Mechanism dissection found ASC-J9(r) could suppress significantly the FASN expression and FASN-mediated PCa progression via the AR-dependent pathway involving AR->SREBP-1->FASN signaling in AR-positive C4-2 and LNCaP cells and via the AR-independent pathway involving the modulation of PI3K/AKT->SREBP-1->FASN signaling in AR-negative PC-3 and DU145 cells. Together, these results suggest that FASN is one of the important mechanism why the current ADT eventually fails. ASC-J9(r) might represent a new potential therapeutic approach to suppress FASN mediated PCa progression via both AR-dependent and AR-independent pathways during the castration resistant stage of PCa. (c) 2016 Wiley Periodicals, Inc. PMID- 26894510 TI - Retinotopic encoding of the Ternus-Pikler display reflected in the early visual areas. AB - The visual representation of the world is often assumed to be retinotopic, and many visual brain areas are indeed organized retinotopically. Visual perception, however, is not based on a reference frame anchored in retinotopic coordinates. For example, when an object moves, motion of its constituent parts is perceived relative to the object rather than in retinotopic coordinates. The moving object thus serves as a nonretinotopic reference system for computing the properties of its parts. It is largely unknown how the brain accomplishes this feat. Here, we used the Ternus-Pikler display to pit retinotopic processing in a stationary reference system against nonretinotopic processing in a moving one. Using 7T fMRI, we found that the average blood-oxygen-level dependent activations in V1, V2, and V3 reflected the retinotopic properties, but not the nonretinotopic percepts, of the Ternus-Pikler display. In the human motion processing complex (hMT+), activations were compatible with both retinotopic and nonretinotopic encoding. Thus, hMT+ may be the first visual area encoding the nonretinotopic percepts of the Ternus-Pikler display. PMID- 26894511 TI - Mobile gaze tracking system for outdoor walking behavioral studies. AB - Most gaze tracking techniques estimate gaze points on screens, on scene images, or in confined spaces. Tracking of gaze in open-world coordinates, especially in walking situations, has rarely been addressed. We use a head-mounted eye tracker combined with two inertial measurement units (IMU) to track gaze orientation relative to the heading direction in outdoor walking. Head movements relative to the body are measured by the difference in output between the IMUs on the head and body trunk. The use of the IMU pair reduces the impact of environmental interference on each sensor. The system was tested in busy urban areas and allowed drift compensation for long (up to 18 min) gaze recording. Comparison with ground truth revealed an average error of 3.3 degrees while walking straight segments. The range of gaze scanning in walking is frequently larger than the estimation error by about one order of magnitude. Our proposed method was also tested with real cases of natural walking and it was found to be suitable for the evaluation of gaze behaviors in outdoor environments. PMID- 26894513 TI - The transfer of motion direction learning to an opposite direction enabled by double training: A reply to Liang et al. (2015). AB - A recent paper from our lab (Zhang & Yang, 2014) reports that perceptual learning of motion-direction discrimination, which is known to be specific to the trained direction, can transfer significantly, and sometimes completely, to an opposite direction, provided that the observers receive additional exposure of the opposite direction via an irrelevant task. However, in a newly published study, Zili Liu and collaborators claim that they cannot replicate our original double training results using identical procedures (Liang, Fahle, & Liu, 2015). Here we point out that the relevant data in Liang et al. (2015) are actually not very different from those in Zhang and Yang (2014). We thus pool data from both studies to obtain a more precise estimate of the transfer rate, which is over 75% of the learning effect. PMID- 26894512 TI - A solid frame for the window on cognition: Modeling event-related pupil responses. AB - Pupil size is often used to infer central processes, including attention, memory, and emotion. Recent research has spotlighted its relation to behavioral variables from decision-making models and to neural variables such as locus coeruleus activity and cortical oscillations. As yet, a unified and principled approach for analyzing pupil responses is lacking. Here we seek to establish a formal, quantitative forward model for pupil responses by describing them with linear time-invariant systems. Based on empirical data from human participants, we show that a combination of two linear time-invariant systems can parsimoniously explain approximately all variance evoked by illuminance changes. Notably, the model makes a counterintuitive prediction that pupil constriction dominates the responses to darkness flashes, as in previous empirical reports. This prediction was quantitatively confirmed for responses to light and darkness flashes in an independent group of participants. Crucially, illuminance- and nonilluminance related inputs to the pupillary system are presumed to share a common final pathway, composed of muscles and nerve terminals. Hence, we can harness our illuminance-based model to estimate the temporal evolution of this neural input for an auditory-oddball task, an emotional-words task, and a visual-detection task. Onset and peak latencies of the estimated neural inputs furnish plausible hypotheses for the complexity of the underlying neural circuit. To conclude, this mathematical description of pupil responses serves as a prerequisite to refining their relation to behavioral and brain indices of cognitive processes. PMID- 26894514 TI - Out-of-pocket payments and community-wide health outcomes: an examination of influenza vaccination subsidies in Japan. AB - While studies have shown that reductions in out-of-pocket payments for vaccination generally encourages vaccination uptake, research on the impact on health outcomes has rarely been examined. Thus, the present study, using municipal-level survey data on a subsidy programme for influenza vaccination in Japan that covers the entire country, examines how reductions in out-of-pocket payments for vaccination among non-elderly individuals through a subsidy programme affected regional-level influenza activity. We find that payment reductions are negatively correlated with the number of weeks with a high influenza alert in that region, although the correlation varied across years. At the same time, we find no significant correlation between payment reductions and the total duration of influenza outbreaks (i.e. periods with a moderate or high alert). Given that a greater number of weeks with a high alert indicates a severer epidemic, our findings suggest that reductions in out-of-pocket payments for influenza vaccination among the non-elderly had a positive impact on community-wide health outcomes, indicating that reduced out-of-pocket payments contributes to the effective control of severe influenza epidemics. This suggests that payment reductions could benefit not only individuals by providing them with better access to preventive care, as has been shown previously, but also communities as a whole by shortening the duration of epidemics. PMID- 26894515 TI - Introduction to the ISRHML 2016 Abstracts. PMID- 26894516 TI - Treatment options for moderate-to-very severe chronic obstructive pulmonary disease. AB - INTRODUCTION: The appropriate drug management of COPD is still based on the use of bronchodilators, possibly associated with an anti-inflammatory agent. However, there are still fundamental questions that require clarification to optimise their use and major unmet clinical needs that must be addressed. AREAS COVERED: The advances obtained with the pharmacological options currently consolidated and the different approaches that are often used in an attempt to respond to unmet therapeutic needs are reviewed Expert opinion: In view of the unsatisfactory status of current treatments for COPD, there is an urgent need for alternative and more effective therapeutic approaches that will help to relieve patient symptoms and affect the natural course of COPD, inhibiting chronic inflammation and reversing the disease process or preventing its progression. However, new pharmacologic options have proved difficult to develop. Therefore, it is mandatory to optimize the use of the treatment options at our disposal. However, there are still fundamental questions regarding their use, including the step-up and step-down pharmacological approach, that require clarification to optimise the use of these drugs. It is likely that phenotyping COPD patients would help in identifying the right treatment for each COPD patient and improve the effectiveness of therapies. PMID- 26894517 TI - Pediatric isolated thoracic and/or lumbar transverse and spinous process fractures. AB - OBJECTIVE Isolated transverse and spinous process fractures (TPFx and SPFx) in the thoracic and/or lumbar region have been deemed clinically insignificant in the adult population. This same rule is often applied to the pediatric population; however, little evidence exists in this younger group. The goal of this study was to describe the clinical, radiographic, and long-term data on isolated TPFx and SPFx in an exclusively pediatric population. METHODS A retrospective chart review at Monroe Carell Jr. Children's Hospital at Vanderbilt University identified 82 pediatric patients with isolated TPFx and/or SPFx following a traumatic event between January 2000 and December 2013. Patient demographic information, presenting symptoms, radiographic characteristics, and follow-up data were collected. Follow-up was used to determine the outcome (presence of neurological deficits) of such injuries via complete physical examination and, when available, radiographic evidence. RESULTS In the 82 identified patients, the mean age was 15.5 +/- 3.1 years (mean is expressed +/- SD throughout), with 72 injuries (87.8%) resulting from a motor vehicle, motorcycle, or all-terrain vehicle accident. There was a mean of 1.7 +/- 1.0 fractured vertebral levels involved and a mean of 1.8 +/- 1.1 fractures was identified per patient. Seventy-one patients (86.6%) needed bedside pain control, 7 (8.5%) were prescribed a brace, and 4 patients (4.9%) received a collar. Physical therapy was recommended for 12 patients (14.6%). A total of 84.1% had follow-up, and the mean length of follow-up was 19 +/- 37 months. No patients had true neurological deficits at presentation or follow-up as a result of their isolated fractures, whereas 95.1% had other associated system injuries. CONCLUSIONS These data shows that there is no appreciable long-term complication associated with isolated thoracic and/or lumbar TPFx and/or SPFx in an exclusively pediatric population. Because these fractures are, however, associated with high-energy blunt trauma, they often result in associated soft tissue or other skeletal injury. All pediatric patients in the cohort benefited from conservative management and aggressive treatment of their comorbidities. PMID- 26894519 TI - Management of the temporal muscle during cranioplasty: technical note. AB - Over the past 2 decades there has been a resurgence of interest in the use of decompressive craniectomy in the management of neurological emergencies. While technically straightforward, the procedure is associated with a number of complications relating to the initial decompression and subsequent cranioplasty. One complication that has received relatively little attention relates to the management of the temporal muscle. Here, through an illustrative case, the author describes a novel method of minimizing dissection of the temporal muscle during a cranioplasty procedure. Rather than placing a synthetic material over the dura mater to prevent adhesions or dissecting the muscle off the dura, the dura was opened and reflected laterally, pedicled to the temporal muscle. The dural defect was closed with a dural substitute, and the bone flap was secured in a routine fashion. The temporal muscle was then secured in its anatomical position. At the 6-month follow-up, radiological and clinical examination confirmed the restoration of muscle volume with excellent cosmetic and functional results. Opening the dura on a temporal muscle pedicle does not represent a routine form of surgical reconstruction; however, the use of this technique may have some advantages especially in young patients who have made a good recovery and for whom facial aesthetics may be particularly important. PMID- 26894520 TI - Transsacral transdiscal L5-S1 screws for the management of high-grade spondylolisthesis in an adolescent. AB - The surgical management of high-grade spondylolisthesis in adolescents remains a controversial issue. Because the basic procedure, posterolateral fusion, is associated with a significant rate of pseudarthrosis and listhesis progression, there is a pressing need for alternative surgical techniques. In the present report, the authors describe the case of an adolescent patient with significant low-back pain who was found to have Grade IV spondylolisthesis at L5-S1 that was treated with transsacral transdiscal screw fixation. Bilateral pedicle screws were placed starting from the top of the S-1 pedicle, across the L5-S1 intervertebral disc space, and into the L-5 body. At 14 months after surgery, the patient had considerable improvement in his pain and radiographic fusion across L5-S1. The authors conclude that transsacral transdiscal pedicle screws may serve as an efficacious and safe option for the correction of high-grade spondylolisthesis in adolescent patients. PMID- 26894521 TI - Unique presentation of LHON/MELAS overlap syndrome caused by m.13046T>C in MTND5. AB - BACKGROUND: Leber hereditary optic neuropathy (LHON) and mitochondrial encephalopathy, myopathy, lactic acidosis and stroke-like episodes (MELAS) syndromes are mitochondrially inherited disorders characterized by acute visual failure and variable multiorgan system presentation, respectively. MATERIALS AND METHODS: A 12-year-old girl with otherwise unremarkable medical history presented with abrupt, painless loss of vision. Over the next few months, she developed moderate sensorineural hearing loss, vertigo, migraines, anhedonia and thyroiditis. Ocular examination confirmed bilateral optic nerve atrophy. Metabolic workup documented elevated cerebrospinal fluid lactate. Initial genetic analyses excluded the three most common LHON mutations. Subsequently, Sanger sequencing of the entire mitochondrial DNA (mtDNA) genome was performed. RESULTS: Whole mtDNA sequencing revealed a pathogenic heteroplasmic mutation m.13046T>C in MTND5 encoding the ND5 subunit of complex I. This particular variant has previously been described in a single case report of MELAS/Leigh syndrome (subacute necrotizing encephalopathy). Based on the constellation of clinical symptoms in our patient, we diagnose the condition as LHON/MELAS overlap syndrome. CONCLUSIONS: We describe a unique presentation of LHON/MELAS overlap syndrome resulting from a m.13046T>C mutation in a 12-year-old girl. In patients with sudden vision loss in which three of the most prevalent LHON mitochondrial mutations have been ruled out, molecular genetic examination should be extended to other mtDNA-encoded subunits of MTND5 complex I. Furthermore, atypical clinical presentations must be considered, even in well-described phenotypes. PMID- 26894518 TI - Imaging and serum biomarkers reflecting the functional efficacy of extended erythropoietin treatment in rats following infantile traumatic brain injury. AB - OBJECTIVE Traumatic brain injury (TBI) is a leading cause of death and severe morbidity for otherwise healthy full-term infants around the world. Currently, the primary treatment for infant TBI is supportive, as no targeted therapies exist to actively promote recovery. The developing infant brain, in particular, has a unique response to injury and the potential for repair, both of which vary with maturation. Targeted interventions and objective measures of therapeutic efficacy are needed in this special population. The authors hypothesized that MRI and serum biomarkers can be used to quantify outcomes following infantile TBI in a preclinical rat model and that the potential efficacy of the neuro-reparative agent erythropoietin (EPO) in promoting recovery can be tested using these biomarkers as surrogates for functional outcomes. METHODS With institutional approval, a controlled cortical impact (CCI) was delivered to postnatal Day (P)12 rats of both sexes (76 rats). On postinjury Day (PID)1, the 49 CCI rats designated for chronic studies were randomized to EPO (3000 U/kg/dose, CCI-EPO, 24 rats) or vehicle (CCI-veh, 25 rats) administered intraperitoneally on PID1-4, 6, and 8. Acute injury (PID3) was evaluated with an immunoassay of injured cortex and serum, and chronic injury (PID13-28) was evaluated with digitized gait analyses, MRI, and serum immunoassay. The CCI-veh and CCI-EPO rats were compared with shams (49 rats) primarily using 2-way ANOVA with Bonferroni post hoc correction. RESULTS Following CCI, there was 4.8% mortality and 55% of injured rats exhibited convulsions. Of the injured rats designated for chronic analyses, 8.1% developed leptomeningeal cyst-like lesions verified with MRI and were excluded from further study. On PID3, Western blot showed that EPO receptor expression was increased in the injured cortex (p = 0.008). These Western blots also showed elevated ipsilateral cortex calpain degradation products for alphaII spectrin (alphaII-SDPs; p < 0.001), potassium chloride cotransporter 2 (KCC2-DPs; p = 0.037), and glial fibrillary acidic protein (GFAP-DPs; p = 0.002), as well as serum GFAP (serum GFAP-DPs; p = 0.001). In injured rats multiplex electrochemiluminescence analyses on PID3 revealed elevated serum tumor necrosis factor alpha (TNFalpha p = 0.01) and chemokine (CXC) ligand 1 (CXCL1). Chronically, that is, in PID13-16 CCI-veh rats, as compared with sham rats, gait deficits were demonstrated (p = 0.033) but then were reversed (p = 0.022) with EPO treatment. Diffusion tensor MRI of the ipsilateral and contralateral cortex and white matter in PID16-23 CCI-veh rats showed widespread injury and significant abnormalities of functional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD); MD, AD, and RD improved after EPO treatment. Chronically, P13-P28 CCI-veh rats also had elevated serum CXCL1 levels, which normalized in CCI-EPO rats. CONCLUSIONS Efficient translation of emerging neuro-reparative interventions dictates the use of age-appropriate preclinical models with human clinical trial-compatible biomarkers. In the present study, the authors showed that CCI produced chronic gait deficits in P12 rats that resolved with EPO treatment and that chronic imaging and serum biomarkers correlated with this improvement. PMID- 26894522 TI - Changes in White Matter Microstructure Suggest an Inflammatory Origin of Neuropsychiatric Systemic Lupus Erythematosus. AB - OBJECTIVE: To assess white matter (WM) and gray matter (GM) magnetization transfer ratio histogram peak heights (MTR-HPHs) in different subsets of patients with neuropsychiatric systemic lupus erythematosus (NPSLE) who have unremarkable findings on 3T magnetic resonance imaging of the brain and to evaluate whether these values could be used to highlight different clinically suspected underlying pathogenic processes or identify the clinical NPSLE status or whether they could be associated with a specific NPSLE syndrome. METHODS: Sixty-four SLE patients with neuropsychiatric symptoms were included. The initial NPSLE diagnosis and suspected underlying pathogenic process were established by multidisciplinary evaluation. The final diagnosis was made after also considering the disease course 6-18 months later. Thirty-three patients with central nervous system (CNS) NPSLE and 31 SLE patients with neuropsychiatric symptoms unrelated to SLE (non SLE-related NP) were included. Twenty SLE patients without neuropsychiatric symptoms and 36 healthy control subjects were included for comparison. Differences in the WM and GM mean MTR-HPHs and between the different NPSLE subgroups (CNS NPSLE diagnosis, NPSLE phenotype [inflammatory or ischemic], and clinical changes after treatment) and the relationship to NPSLE syndromes were evaluated. RESULTS: Patients with inflammatory NPSLE had significantly lower WM MTR-HPHs than did the healthy controls, the SLE patients, and the non-SLE-related NP patients. Cognitive disorder, mood disorder, and psychosis were related to lower WM MTR-HPH values and cerebrovascular symptoms to higher values. Furthermore, the mean MTR-HPHs in the WM increased when the clinical status of the NPSLE patients improved. CONCLUSION: Measurement of MTR-HPH of the WM has the potential to identify inflammatory NPSLE with CNS involvement. This finding underscores the usefulness of this technique for the detection of cerebral changes in NPSLE patients and for the assessment of clinical changes after treatment. PMID- 26894523 TI - A monolithic MEMS position sensor for closed-loop high-speed atomic force microscopy. AB - The accuracy and repeatability of atomic force microscopy (AFM) imaging significantly depend on the accuracy of the piezoactuator. However, nonlinear properties of piezoactuators can distort the image, necessitating sensor-based closed-loop actuators to achieve high accuracy AFM imaging. The advent of high speed AFM has made the requirements on the position sensors in such a system even more stringent, requiring higher bandwidths and lower sensor mass than traditional sensors can provide. In this paper, we demonstrate a way for high speed, high-precision closed-loop AFM nanopositioning using a novel, miniaturized micro-electro-mechanical system position sensor in conjunction with a simple PID controller. The sensor was developed to respond to the need for small, lightweight, high-bandwidth, long-range and sub-nm-resolution position measurements in high-speed AFM applications. We demonstrate the use of this sensor for closed-loop operation of conventional as well as high-speed AFM operation to provide distortion-free images. The presented implementation of this closed-loop approach allows for positioning precision down to 2.1 A, reduces the integral nonlinearity to below 0.2%, and allows for accurate closed loop imaging at line rates up to 300 Hz. PMID- 26894524 TI - Gersemiols A-C and Eunicellol A, Diterpenoids from the Arctic Soft Coral Gersemia fruticosa. AB - Three new diterpenes named gersemiols A-C (1-3) and a new eunicellane diterpene, eunicellol A (4), have been isolated together with the known sesquiterpene (+) alpha-muurolene (5) from the Arctic soft coral Gersemia fruticosa. The name gersemiane was assigned to the rare and unnamed diterpene skeleton of compounds 1 3 corresponding to 4-isopropyl-1,5,8a-trimethyltetradecahydrophenanthrene. The chemical structures were elucidated on the basis of extensive spectroscopic analysis (HR-ESIMS, 1D and 2D NMR) as well as coupling constant calculations for the determination of the relative configurations. All compounds were tested for their antimicrobial activity against several bacteria and fungi and eunicellol A was found to exhibit moderate and selective antibacterial activity. PMID- 26894525 TI - Assessment of Sexual Dysfunction Symptoms in Female Drug Users: Standardized vs. Unstandardized Methods. AB - AIMS: The aim of this study is to evaluate whether there is a difference in the identified prevalence between the assessment of symptoms of sexual dysfunction in female drug users using a standardized scale and by means of a nonstandardized set of questions about sexual dysfunctions. METHOD: A cross-sectional study was conducted with two groups of substance-dependent women using the Drug Abuse Screening Test, the Short Alcohol Dependence Data questionnaire, the Fagerstrom Test for Nicotine Dependence for the evaluation of the severity of dependence, and the Arizona Sexual Experience Scale. FINDINGS: In both groups, the severity of dependence and the prevalence of symptoms of sexual dysfunctions in women were similar. CONCLUSION: The use of standardized and nonstandardized instruments to assess sexual dysfunction symptoms is an essential resource for the provision of good-quality care to this clientele. PMID- 26894527 TI - Direct Access Telemedicine. PMID- 26894526 TI - Biological roles of KGF, CTGF and TGF-beta in cyclosporine-A- and phenytoin- induced gingival overgrowth: A comparative experimental animal study. AB - OBJECTIVE: To identify the possible biological roles of keratinocyte growth factor (KGF), connective tissue growth factor (CTGF) and transforming growth factor-beta (TGF-beta) in cyclosporine-A (CsA) and phenytoin (PNT)-induced gingival overgrowth (GO) and to correlate them with each other. METHODS: Sixty adult male albino rats were selected and divided into 3 equal groups. Group I rats received no treatment. Group II rats were administrated CsA for 7 weeks. Group III were administrated PNT for the same period. Rats were euthanized at the end of the experiment and routine tissue processing was carried out. The obtained specimens were stained with H&E, KGF, CTGF and TGF-beta antibodies. RESULTS: One way MANOVA test for KGF, CTGF and TGF-beta revealed an overall significant difference between the different groups (P<0.001). LSD post hoc test for multiple comparisons revealed a significant difference between each two groups. Two-tailed Pearson correlation for group II revealed non-significant weak positive correlations between KGF & CTGF and between CTGF & TGF-beta. Non-significant weak negative correlation was found between KGF & TGF-beta. Meanwhile, group III revealed non-significant weak positive correlation between KGF & TGF-beta and between CTGF & TGF-beta. Significant moderate positive correlation was found between KGF & CTGF. CONCLUSION: The findings of the present study indicated that KGF, CTGF and TGF-beta have biological roles in progression of CsA- and PNT- induced GO. KGF plays a greater role in CsA- induced GO than in PNT- induced GO. Meanwhile, CTGF and TGF-beta play a role in PNT- induced GO greater than in CsA- induced GO. PMID- 26894528 TI - Expanding beyond biological crystallography. PMID- 26894530 TI - Structure of D-alanine-D-alanine ligase from Yersinia pestis: nucleotide phosphate recognition by the serine loop. AB - D-Alanyl-D-alanine is an essential precursor of bacterial peptidoglycan and is synthesized by D-alanine-D-alanine ligase (DDL) with hydrolysis of ATP; this reaction makes DDL an important drug target for the development of antibacterial agents. Five crystal structures of DDL from Yersinia pestis (YpDDL) were determined at 1.7-2.5 A resolution: apo, AMP-bound, ADP-bound, adenosine 5' (beta,gamma-imido)triphosphate-bound, and D-alanyl-D-alanine- and ADP-bound structures. YpDDL consists of three domains, in which four loops, loop 1, loop 2 (the serine loop), loop 3 (the omega-loop) and loop 4, constitute the binding sites for two D-alanine molecules and one ATP molecule. Some of them, especially the serine loop and the omega-loop, show flexible conformations, and the serine loop is mainly responsible for the conformational change in substrate nucleotide phosphates. Enzyme-kinetics assays were carried out for both the D-alanine and ATP substrates and a substrate-binding mechanism was proposed for YpDDL involving conformational changes of the loops. PMID- 26894531 TI - The structure of VgrG1 from Pseudomonas aeruginosa, the needle tip of the bacterial type VI secretion system. AB - The type VI secretion system (T6SS) is a mechanism that is commonly used by pathogenic bacteria to infect host cells and for survival in competitive environments. This system assembles on a core baseplate and elongates like a phage puncturing device; it is thought to penetrate the target membrane and deliver effectors into the host or competing bacteria. Valine-glycine repeat protein G1 (VgrG1) forms the spike at the tip of the elongating tube formed by haemolysin co-regulated protein 1 (Hcp1); it is structurally similar to the T4 phage (gp27)3-(gp5)3 puncturing complex. Here, the crystal structure of full length VgrG1 from Pseudomonas aeruginosa is reported at a resolution of 2.0 A, which through a trimeric arrangement generates a needle-like shape composed of two main parts, the head and the spike, connected via a small neck region. The structure reveals several remarkable structural features pointing to the possible roles of the two main segments of VgrG1: the head as a scaffold cargo domain and the beta-roll spike with implications in the cell-membrane puncturing process and as a carrier of cognate toxins. PMID- 26894529 TI - High-density grids for efficient data collection from multiple crystals. AB - Higher throughput methods to mount and collect data from multiple small and radiation-sensitive crystals are important to support challenging structural investigations using microfocus synchrotron beamlines. Furthermore, efficient sample-delivery methods are essential to carry out productive femtosecond crystallography experiments at X-ray free-electron laser (XFEL) sources such as the Linac Coherent Light Source (LCLS). To address these needs, a high-density sample grid useful as a scaffold for both crystal growth and diffraction data collection has been developed and utilized for efficient goniometer-based sample delivery at synchrotron and XFEL sources. A single grid contains 75 mounting ports and fits inside an SSRL cassette or uni-puck storage container. The use of grids with an SSRL cassette expands the cassette capacity up to 7200 samples. Grids may also be covered with a polymer film or sleeve for efficient room temperature data collection from multiple samples. New automated routines have been incorporated into the Blu-Ice/DCSS experimental control system to support grids, including semi-automated grid alignment, fully automated positioning of grid ports, rastering and automated data collection. Specialized tools have been developed to support crystallization experiments on grids, including a universal adaptor, which allows grids to be filled by commercial liquid-handling robots, as well as incubation chambers, which support vapor-diffusion and lipidic cubic phase crystallization experiments. Experiments in which crystals were loaded into grids or grown on grids using liquid-handling robots and incubation chambers are described. Crystals were screened at LCLS-XPP and SSRL BL12-2 at room temperature and cryogenic temperatures. PMID- 26894532 TI - Lattice filter for processing image data of three-dimensional protein nanocrystals. AB - When 300 kV cryo-EM images at Scherzer focus are acquired from ~ 100 nm thick three-dimensional protein nanocrystals using a Falcon 2 direct electron detector, Fourier transformation can reveal the crystalline lattice to surprisingly high resolutions, even though the images themselves seem to be devoid of any contrast. Here, it is reported how this lattice information can be enhanced by means of a wave finder in combination with Wiener-type maximum-likelihood filtering. This procedure paves the way towards full three-dimensional structure determination at high resolution for protein crystals. PMID- 26894533 TI - Structure of the ectodomain of the electron transporter Rv2874 from Mycobacterium tuberculosis reveals a thioredoxin-like domain combined with a carbohydrate binding module. AB - The members of the CcdA family are integral membrane proteins that use a disulfide cascade to transport electrons from the thioredoxin-thioredoxin reductase system in the interior of the cell into the extracytoplasmic space. The core transmembrane portion of this family is often elaborated with additional hydrophilic domains that act as adapters to deliver reducing potential to targets outside the cellular membrane. To investigate the function of family members in Mycobacterium tuberculosis, the structure of the C-terminal ectodomain from Rv2874, one of three CcdA-family members present in the genome, was determined. The crystal structure, which was refined at 1.9 A resolution with R = 0.195 and Rfree = 0.219, reveals the predicted thioredoxin-like domain with its conserved Cys-X-X-Cys active-site motif. Unexpectedly, this domain is combined with a second domain with a carbohydrate-binding module (CBM) fold, this being the first reported example of a CBM in association with a thioredoxin-like domain fold. A cavity in the CBM adjacent to the thioredoxin active site suggests a likely carbohydrate-binding site, representing a broadening of the substrate range for CcdA-family members and an expansion of the thioredoxin-domain functionality to carbohydrate modification. PMID- 26894535 TI - Bacillus licheniformis trehalose-6-phosphate hydrolase structures suggest keys to substrate specificity. AB - Trehalose-6-phosphate hydrolase (TreA) belongs to glycoside hydrolase family 13 (GH13) and catalyzes the hydrolysis of trehalose 6-phosphate (T6P) to yield glucose and glucose 6-phosphate. The products of this reaction can be further metabolized by the energy-generating glycolytic pathway. Here, crystal structures of Bacillus licheniformis TreA (BlTreA) and its R201Q mutant complexed with p nitrophenyl-alpha-D-glucopyranoside (R201Q-pPNG) are presented at 2.0 and 2.05 A resolution, respectively. The overall structure of BlTreA is similar to those of other GH13 family enzymes. However, detailed structural comparisons revealed that the catalytic site of BlTreA contains a long loop that adopts a different conformation from those of other GH13 family members. Unlike the homologous regions of Bacillus cereus oligo-1,6-glucosidase (BcOgl) and Erwinia rhapontici isomaltulose synthase (NX-5), the surface potential of the BlTreA active site exhibits a largely positive charge contributed by the four basic residues His281, His282, Lys284 and Lys292. Mutation of these residues resulted in significant decreases in the enzymatic activity of BlTreA. Strikingly, the (281)HHLK(284) motif and Lys292 play critical roles in substrate discrimination by BlTreA. PMID- 26894536 TI - A technique for determining the deuterium/hydrogen contrast map in neutron macromolecular crystallography. AB - A difference in the neutron scattering length between hydrogen and deuterium leads to a high density contrast in neutron Fourier maps. In this study, a technique for determining the deuterium/hydrogen (D/H) contrast map in neutron macromolecular crystallography is developed and evaluated using ribonuclease A. The contrast map between the D2O-solvent and H2O-solvent crystals is calculated in real space, rather than in reciprocal space as performed in previous neutron D/H contrast crystallography. The present technique can thus utilize all of the amplitudes of the neutron structure factors for both D2O-solvent and H2O-solvent crystals. The neutron D/H contrast maps clearly demonstrate the powerful detectability of H/D exchange in proteins. In fact, alternative protonation states and alternative conformations of hydroxyl groups are observed at medium resolution (1.8 A). Moreover, water molecules can be categorized into three types according to their tendency towards rotational disorder. These results directly indicate improvement in the neutron crystal structure analysis. This technique is suitable for incorporation into the standard structure-determination process used in neutron protein crystallography; consequently, more precise and efficient determination of the D-atom positions is possible using a combination of this D/H contrast technique and standard neutron structure-determination protocols. PMID- 26894534 TI - Molecular architecture of the nucleoprotein C-terminal domain from the Ebola and Marburg viruses. AB - The Filoviridae family of negative-sense, single-stranded RNA (ssRNA) viruses is comprised of two species of Marburgvirus (MARV and RAVV) and five species of Ebolavirus, i.e. Zaire (EBOV), Reston (RESTV), Sudan (SUDV), Tai Forest (TAFV) and Bundibugyo (BDBV). In each of these viruses the ssRNA encodes seven distinct proteins. One of them, the nucleoprotein (NP), is the most abundant viral protein in the infected cell and within the viral nucleocapsid. It is tightly associated with the viral RNA in the nucleocapsid, and during the lifecycle of the virus is essential for transcription, RNA replication, genome packaging and nucleocapsid assembly prior to membrane encapsulation. The structure of the unique C-terminal globular domain of the NP from EBOV has recently been determined and shown to be structurally unrelated to any other known protein [Dziubanska et al. (2014), Acta Cryst. D70, 2420-2429]. In this paper, a study of the C-terminal domains from the NP from the remaining four species of Ebolavirus, as well as from the MARV strain of Marburgvirus, is reported. As expected, the crystal structures of the BDBV and TAFV proteins show high structural similarity to that from EBOV, while the MARV protein behaves like a molten globule with a core residual structure that is significantly different from that of the EBOV protein. PMID- 26894537 TI - Atomic resolution experimental phase information reveals extensive disorder and bound 2-methyl-2,4-pentanediol in Ca(2+)-calmodulin. AB - Calmodulin (CaM) is the primary calcium signaling protein in eukaryotes and has been extensively studied using various biophysical techniques. Prior crystal structures have noted the presence of ambiguous electron density in both hydrophobic binding pockets of Ca(2+)-CaM, but no assignment of these features has been made. In addition, Ca(2+)-CaM samples many conformational substates in the crystal and accurately modeling the full range of this functionally important disorder is challenging. In order to characterize these features in a minimally biased manner, a 1.0 A resolution single-wavelength anomalous diffraction data set was measured for selenomethionine-substituted Ca(2+)-CaM. Density-modified electron-density maps enabled the accurate assignment of Ca(2+)-CaM main-chain and side-chain disorder. These experimental maps also substantiate complex disorder models that were automatically built using low-contour features of model phased electron density. Furthermore, experimental electron-density maps reveal that 2-methyl-2,4-pentanediol (MPD) is present in the C-terminal domain, mediates a lattice contact between N-terminal domains and may occupy the N-terminal binding pocket. The majority of the crystal structures of target-free Ca(2+)-CaM have been derived from crystals grown using MPD as a precipitant, and thus MPD is likely to be bound in functionally critical regions of Ca(2+)-CaM in most of these structures. The adventitious binding of MPD helps to explain differences between the Ca(2+)-CaM crystal and solution structures and is likely to favor more open conformations of the EF-hands in the crystal. PMID- 26894538 TI - In meso in situ serial X-ray crystallography of soluble and membrane proteins at cryogenic temperatures. AB - Here, a method for presenting crystals of soluble and membrane proteins growing in the lipid cubic or sponge phase for in situ diffraction data collection at cryogenic temperatures is introduced. The method dispenses with the need for the technically demanding and inefficient crystal-harvesting step that is an integral part of the lipid cubic phase or in meso method of growing crystals. Crystals are dispersed in a bolus of mesophase sandwiched between thin plastic windows. The bolus contains tens to hundreds of crystals, visible with an in-line microscope at macromolecular crystallography synchrotron beamlines and suitably disposed for conventional or serial crystallographic data collection. Wells containing the crystal-laden boluses are removed individually from hermetically sealed glass plates in which crystallization occurs, affixed to pins on goniometer bases and excess precipitant is removed from around the mesophase. The wells are snap cooled in liquid nitrogen, stored and shipped in Dewars, and manually or robotically mounted on a goniometer in a cryostream for diffraction data collection at 100 K, as is performed routinely with standard, loop-harvested crystals. The method is a variant on the recently introduced in meso in situ serial crystallography (IMISX) method that enables crystallographic measurements at cryogenic temperatures where crystal lifetimes are enormously enhanced whilst reducing protein consumption dramatically. The new approach has been used to generate high-resolution crystal structures of a G-protein-coupled receptor, alpha-helical and beta-barrel transporters and an enzyme as model integral membrane proteins. Insulin and lysozyme were used as test soluble proteins. The quality of the data that can be generated by this method was attested to by performing sulfur and bromine SAD phasing with two of the test proteins. PMID- 26894539 TI - Crystal structures of the components of the Staphylococcus aureus leukotoxin ED. AB - Staphylococcal leukotoxins are a family of beta-barrel, bicomponent, pore-forming toxins with membrane-damaging functions. These bacterial exotoxins share sequence and structural homology and target several host-cell types. Leukotoxin ED (LukED) is one of these bicomponent pore-forming toxins that Staphylococcus aureus produces in order to suppress the ability of the host to contain the infection. The recent delineation of the important role that LukED plays in S. aureus pathogenesis and the identification of its protein receptors, combined with its presence in S. aureus methicillin-resistant epidemic strains, establish this leukocidin as a possible target for the development of novel therapeutics. Here, the crystal structures of the water-soluble LukE and LukD components of LukED have been determined. The two structures illustrate the tertiary-structural variability with respect to the other leukotoxins while retaining the conservation of the residues involved in the interaction of the protomers in the bipartite leukotoxin in the pore complex. PMID- 26894540 TI - Probing the effectiveness of spectroscopic reporter unnatural amino acids: a structural study. AB - The X-ray crystal structures of superfolder green fluorescent protein (sfGFP) containing the spectroscopic reporter unnatural amino acids (UAAs) 4-cyano-L phenylalanine (pCNF) or 4-ethynyl-L-phenylalanine (pCCF) at two unique sites in the protein have been determined. These UAAs were genetically incorporated into sfGFP in a solvent-exposed loop region and/or a partially buried site on the beta barrel of the protein. The crystal structures containing the UAAs at these two sites permit the structural implications of UAA incorporation for the native protein structure to be assessed with high resolution and permit a direct correlation between the structure and spectroscopic data to be made. The structural implications were quantified by comparing the root-mean-square deviation (r.m.s.d.) between the crystal structure of wild-type sfGFP and the protein constructs containing either pCNF or pCCF in the local environment around the UAAs and in the overall protein structure. The results suggest that the selective placement of these spectroscopic reporter UAAs permits local protein environments to be studied in a relatively nonperturbative fashion with site specificity. PMID- 26894542 TI - Mask-based approach to phasing of single-particle diffraction data. AB - A Monte Carlo-type approach for low- and medium-resolution phasing of single particle diffraction data is suggested. Firstly, the single-particle phase problem is substituted with the phase problem for an imaginary crystal. A unit cell of this crystal contains a single isolated particle surrounded by a large volume of bulk solvent. The developed phasing procedure then generates a large number of connected and finite molecular masks, calculates their Fourier coefficients, selects the sets with magnitudes that are highly correlated with the experimental values and finally aligns the selected phase sets and calculates the averaged phase values. A test with the known structure of monomeric photosystem II resulted in phases that have 97% correlation with the exact phases in the full 25 A resolution shell (1054 structure factors) and correlations of 99, 94, 81 and 79% for the resolution shells infinity-60, 60-40, 40-30 and 30-25 A, respectively. The same procedure may be used for crystallographic ab initio phasing. PMID- 26894541 TI - Re-refinement of the spliceosomal U4 snRNP core-domain structure. AB - The core domain of small nuclear ribonucleoprotein (snRNP), comprised of a ring of seven paralogous proteins bound around a single-stranded RNA sequence, functions as the assembly nucleus in the maturation of U1, U2, U4 and U5 spliceosomal snRNPs. The structure of the human U4 snRNP core domain was initially solved at 3.6 A resolution by experimental phasing using data with tetartohedral twinning. Molecular replacement from this model followed by density modification using untwinned data recently led to a structure of the minimal U1 snRNP at 3.3 A resolution. With the latter structure providing a search model for molecular replacement, the U4 core-domain structure has now been re-refined. The U4 Sm site-sequence AAUUUUU has been shown to bind to the seven Sm proteins SmF SmE-SmG-SmD3-SmB-SmD1-SmD2 in an identical manner as the U1 Sm-site sequence AAUUUGU, except in SmD1 where the bound U replaces G. The progression from the initial to the re-refined structure exemplifies a tortuous route to accuracy: where well diffracting crystals of complex assemblies are initially unavailable, the early model errors are rectified by exploiting preliminary interpretations in further experiments involving homologous structures. New insights are obtained from the more accurate model. PMID- 26894543 TI - Structure of TSA2 reveals novel features of the active-site loop of peroxiredoxins. AB - Saccharomyces cerevisiae TSA2 belongs to the family of typical 2-Cys peroxiredoxins, a ubiquitously expressed family of redox-active enzymes that utilize a conserved peroxidatic cysteine to reduce peroxides. Typical 2-Cys peroxiredoxins have been shown to be involved in protection against oxidative stress and in hydrogen peroxide signalling. Furthermore, several 2-Cys peroxiredoxins, including S. cerevisiae TSA1 and TSA2, are able to switch to chaperone activity upon hyperoxidation of their peroxidatic cysteine. This makes the sensitivity to hyperoxidation of the peroxidatic cysteine a very important determinant for the cellular function of a peroxiredoxin under different cellular conditions. Typical 2-Cys peroxiredoxins exist as dimers, and in the course of the reaction the peroxidatic cysteine forms a disulfide with a resolving cysteine located in the C-terminus of its dimeric partner. This requires a local unfolding of the active site and the C-terminus. The balance between the fully folded and locally unfolded conformations is of key importance for the reactivity and sensitivity to hyperoxidation of the different peroxiredoxins. Here, the structure of a C48S mutant of TSA2 from S. cerevisiae that mimics the reduced state of the peroxidatic cysteine has been determined. The structure reveals a novel conformation for the strictly conserved Pro41, which is likely to affect the delicate balance between the fully folded and locally unfolded conformations of the active site, and therefore the reactivity and the sensitivity to hyperoxidation. Furthermore, the structure also explains the observed difference in the pKa values of the peroxidatic cysteines of S. cerevisiae TSA1 and TSA2 despite their very high sequence identity. PMID- 26894544 TI - Structures of designed armadillo-repeat proteins show propagation of inter-repeat interface effects. AB - The armadillo repeat serves as a scaffold for the development of modular peptide recognition modules. In order to develop such a system, three crystal structures of designed armadillo-repeat proteins with third-generation N-caps (YIII-type), four or five internal repeats (M-type) and second-generation C-caps (AII-type) were determined at 1.8 A (His-YIIIM4AII), 2.0 A (His-YIIIM5AII) and 1.95 A (YIIIM5AII) resolution and compared with those of variants with third-generation C-caps. All constructs are full consensus designs in which the internal repeats have exactly the same sequence, and hence identical conformations of the internal repeats are expected. The N-cap and internal repeats M1 to M3 are indeed extremely similar, but the comparison reveals structural differences in internal repeats M4 and M5 and the C-cap. These differences are caused by long-range effects of the C-cap, contacting molecules in the crystal, and the intrinsic design of the repeat. Unfortunately, the rigid-body movement of the C-terminal part impairs the regular arrangement of internal repeats that forms the putative peptide-binding site. The second-generation C-cap improves the packing of buried residues and thereby the stability of the protein. These considerations are useful for future improvements of an armadillo-repeat-based peptide-recognition system. PMID- 26894545 TI - A new default restraint library for the protein backbone in Phenix: a conformation-dependent geometry goes mainstream. AB - Chemical restraints are a fundamental part of crystallographic protein structure refinement. In response to mounting evidence that conventional restraints have shortcomings, it has previously been documented that using backbone restraints that depend on the protein backbone conformation helps to address these shortcomings and improves the performance of refinements [Moriarty et al. (2014), FEBS J. 281, 4061-4071]. It is important that these improvements be made available to all in the protein crystallography community. Toward this end, a change in the default geometry library used by Phenix is described here. Tests are presented showing that this change will not generate increased numbers of outliers during validation, or deposition in the Protein Data Bank, during the transition period in which some validation tools still use the conventional restraint libraries. PMID- 26894547 TI - Decreased Glycemic Difference Between Diabetes and Nondiabetes in the Elderly Leads to the Reduced Diagnostic Accuracy of Hemoglobin A1c for Diabetes Screening in an Aged Chinese Population. AB - BACKGROUND: This study investigated the impact of age on the accuracy of glycated hemoglobin (HbA1c) for diabetes screening and explored the possible cause(s). MATERIALS AND METHODS: Data from 3,050 Chinese participants 25-75 years of age without known diabetes in a population-based cross-sectional survey were analyzed. Diabetes was diagnosed by the oral glucose tolerance test (OGTT). The performance of HbA1c for detecting OGTT-defined diabetes in tertile groups (divided by age) was evaluated by the area under the curve (AUC) of the receiver operating characteristic curve (ROC). The effect of age on the difference in glucose levels between participants with and without diabetes and the impact of this difference on the performance of HbA1c were evaluated. RESULTS: In young (25 41 years old), middle-aged (41-53 years old), and old (55-72 years old) participants, the ROC AUC (95% confidence interval) of HbA1c for detecting OGTT defined diabetes was 0.958 (0.915, 1.000), 0.891 (0.852, 0.930), and 0.861 (0.821, 0.901), respectively (P = 0.005). The difference of fasting plasma glucose between participants with diabetes and those without diabetes decreased with increasing age: 3.01 (2.80, 3.22) mmol/L, 2.90 (2.71, 3.09) mmol/L, and 2.33 (2.16, 2.50) mmol/L in the three consecutive age groups, respectively. A similar pattern was found in 2-h postprandial plasma glucose. The impact of age on the diagnostic power of HbA1c diminished after data were rearranged to artificially increase the difference between participants without diabetes and those with diabetes. CONCLUSIONS: The accuracy of HbA1c for detecting OGTT-defined diabetes declines with age. This is largely due to the decreased separation in glycemic levels between participants with diabetes and without diabetes in the elderly. PMID- 26894548 TI - Accurate Lipophilicity (log P) Measurements Inform on Subtle Stereoelectronic Effects in Fluorine Chemistry. AB - Polar exploration: Recently, Linclau and co-workers disclosed a straightforward (19)F-NMR method for determining the log P values of fluorocarbons. The method is particularly useful for most polar compounds and provides a quantitative way to rationalize the more subtle stereoelectronic consequences of fluorine introduction. PMID- 26894549 TI - Structure and Dimensions of Core-Shell Nanoparticles Comparable to the Confocal Volume Studied by Means of Fluorescence Correlation Spectroscopy. AB - In some applications the dye distribution within fluorescently labeled nanoparticles and its stability over long periods of time are important issues. In this article we study numerically and experimentally the applicability of fluorescence correlation spectroscopy (FCS) to resolve such questions. When the size of fluorescently labeled particles is comparable to or larger than the confocal volume, the effective confocal volume seen in FCS experiments is increasing. Such an effect has already been studied for uniformly labeled spherical particles. In this work we analyze the form of the FCS correlation functions (CFs) for core-labeled and shell-labeled core-shell particles. For shell-labeled particles an additional fast decay was found both in simulations and in experiments on custom-made surface-labeled particles. Universal scaling of FCS correlation times based on the squared ratio of the labeled part radius of gyration to the Gaussian radius of the beam profile was found. Recipes based on the analysis of simulated CFs, proposed for interpretation of experimental results, were successfully applied to the FCS results on suspensions of large core-labeled and surface-labeled particles. PMID- 26894550 TI - Time-varying associations between confidence and motivation to abstain from marijuana during treatment among adolescents. AB - INTRODUCTION: An important goal of addictions treatment is to develop a positive association between high levels of confidence and motivation to abstain from substance use. This study modeled the time-varying association between confidence and motivation to abstain from marijuana use among youth in treatment, and the time-varying effect of pre-treatment covariates (marijuana abstinence goal and perceived peer marijuana use) on motivation to abstain. METHOD: 150 adolescents (75% male, 83% White) in community-based intensive outpatient treatment in Pennsylvania completed a pre-treatment assessment of abstinence goal, perceived peer marijuana use, and motivation and confidence to abstain from marijuana. Ratings of motivation and confidence to abstain also were collected after each session. A time-varying effect model (TVEM) was used to characterize changes in the association between confidence and motivation to abstain (lagged), and included covariates representing pre-treatment abstinence goal and perceived peer marijuana use. RESULTS: Confidence and motivation to abstain from marijuana generally increased during treatment. The association between confidence and motivation strengthened across sessions 1-4, and was maintained through later sessions. Pre-treatment abstinence goal had an early time-limited effect (through session 6) on motivation to abstain. Pre-treatment perception of peer marijuana use had a significant effect on motivation to abstain only at session 2. CONCLUSIONS: Early treatment sessions represent a critical period during which the association between confidence and motivation to abstain generally increased. The time-limited effects of pre-treatment characteristics suggest the importance of early sessions in addressing abstinence goal and peer substance use that may impact motivation to abstain from marijuana. PMID- 26894551 TI - A daily process examination of episode-specific drinking to cope motivation among college students. AB - OBJECTIVE: Theory suggests that state- and trait-like factors should interact in predicting drinking to cope (DTC) motivation, yet no research to date has demonstrated this at the drinking episode level of analysis. Thus, we examined whether daily variation in positive and negative affect and avoidance and active coping were associated with DTC motivation during discrete drinking episodes and whether these associations were moderated by tension-reduction expectancies and other person-level risk factors. METHODS: Using a secure website, 722 college student drinkers completed a one-time survey regarding their tension reduction expectancies and then reported daily for 30 days on their affect, coping strategies, drinking behaviors and motives for drinking. RESULTS: Individuals reported higher levels of DTC motivation on days when negative affect and avoidance coping were high and positive affect was low. We found only little support for the predicted interactive effects among the day- and person-level predictors. CONCLUSION: Our results support the state and trait conceptualizations of DTC motivation and provide evidence for the antecedent roles of proximal levels of daily affect and avoidance coping. Our inconsistent results for interaction effects including day-level antecedents raise the possibility that some of these synergistic processes might not generalize across level of analysis. PMID- 26894552 TI - Informing alcohol interventions for student service members/veterans: Normative perceptions and coping strategies. AB - OBJECTIVE: The current study aimed to inform future interventions for heavy alcohol use and problems among college students by examining the utility of normative perceptions and coping strategies in predicting alcohol use among student service members/Veterans (SSM/Vs). METHODS: SSM/Vs and civilian students (N=319) at a large university in the Southern Plains completed self-report measures of demographics, alcohol use and related behaviors, and coping strategies. RESULTS: Both SSM/Vs and civilian students significantly overestimated the typical weekly drinking quantities and frequencies of same-sex students on campus. Among SSM/Vs, normative perceptions of typical student (not military-specific) drinking and substance-related coping strategies significantly predicted drinks consumed per week, while substance-related coping predicted alcohol-related consequences. CONCLUSIONS: Despite the theoretical importance of similarity to normative referents, military-specific norms did not significantly improve the prediction of SSM/Vs' personal drinking behavior. Moreover, neither typical student nor military-specific norms predicted alcohol-related consequences among SSM/Vs after accounting for substance-related coping strategies. Future research may examine the efficacy of descriptive normative feedback and the importance of military-specific norms in alcohol interventions for SSM/Vs. PMID- 26894553 TI - A Global Analysis of the Relationship between Farmed Seaweed Production and Herbivorous Fish Catch. AB - Globally, farmed seaweed production is expanding rapidly in shallow marine habitats. While seaweed farming provides vital income to millions of artisanal farmers, it can negatively impact shallow coral reef and seagrass habitats. However, seaweed farming may also potentially provide food subsidies for herbivorous reef fish such as the Siganidae, a valuable target family, resulting in increased catch. Comparisons of reef fish landings across the central Philippines revealed that the catch of siganids was positively correlated to farmed seaweed production whilst negatively correlated to total reef fish catch over the same period of time. We tested the generality of this pattern by analysing seaweed production, siganid catch, and reef fish catch for six major seaweed-producing countries in the tropics. We hypothesized that increased seaweed production would correspond with increased catch of siganids but not other reef fish species. Analysis of the global data showed a positive correlation between farmed seaweeds and siganids in Southeast Asia (Indonesia, Malaysia, and the Philippines) but not Africa (Tanzania and Zanzibar), or the Western Pacific (Fiji). In Southeast Asia, siganid catch increased disproportionately faster with seaweed production than did reef fish catch. Low continuity, sporadic production and smaller volumes of seaweed farming may explain the differences. PMID- 26894554 TI - Commentary: On Demographic and Personal Characteristics of Male and Female Chairs in Academic Psychiatry. PMID- 26894555 TI - Size-Controlled Synthesis of Porphyrinic Metal-Organic Framework and Functionalization for Targeted Photodynamic Therapy. AB - The understanding of nanomaterials for targeted cancer therapy is of great importance as physical parameters of nanomaterials have been shown to be strong determinants that can promote cellular responses. However, there have been rare platforms that can vastly tune the core of nanoparticles at a molecular level despite various nanomaterials employed in such studies. Here we show targeted photodynamic therapy (PDT) with Zr(IV)-based porphyrinic metal-organic framework (MOF) nanoparticles. Through a bottom-up approach, the size of MOF nanoparticles was precisely tuned in a broad range with a designed functional motif, built upon selection of building blocks of the MOF. In particular, molecular properties of the porphyrinic linker are maintained in the MOF nanoparticles regardless of their sizes. Therefore, size-dependent cellular uptake and ensuing PDT allowed for screening of the optimal size of MOF nanoparticles for PDT while MOF nanoparticle formulation of the photosensitizer showed better PDT efficacy than that of its small molecule. Additionally, Zr6 clusters in the MOF enabled an active targeting modality through postsynthetic modification, giving even more enhanced PDT efficacy. Together with our finding of size controllability covering a broad range in the nano regime, we envision that MOFs can be a promising nanoplatform by adopting advanced small molecule systems into the tunable framework with room for postsynthetic modification. PMID- 26894556 TI - Usefulness of a bioengineered oral mucosa model for preventing palate bone alterations in rabbits with a mucoperiostial defect. AB - The use of mucoperiostial flaps during cleft palate surgery is associated with altered palatal bone growth and development. We analyzed the potential usefulness of a bioengineered oral mucosa in an in vivo model of cleft palate. First, a 4 mm palate defect was created in one side of the palate oral mucosa of 3 week-old New Zealand rabbits, and a complete autologous bioengineered oral mucosa (BOM) or acellular fibrin-agarose scaffold (AS) was implanted. No material was implanted in the negative controls (NC), and positive controls were not subjected to palatal defect (PC). Animals were allowed to grow for 6 months and the results were analyzed morphologically (palate mucosa and bone size) and histologically. Results show that palatal mucosa and bone growth and development were significantly altered in NC and AS animals, whereas BOM animals had similar results to PC and the bioengineered oral mucosa was properly integrated in the host palate. The amount and compaction of collagen fibers was similar between BOM and PC, and both groups of animals had comparable contents of proteoglycans and glycoproteins at the palate bone. No differences were found for decorin, osteocalcin and BMP2. The use of bioengineered oral mucosa substitutes is able to improve palate growth and maturation by preventing the alterations found in animals with denuded palate bone. These results support the potential clinical usefulness of BOM substitutes for the treatment of patients with cleft palate and other conditions in which palate mucosa grafts are necessary with consequent bone denudation. PMID- 26894557 TI - Simultaneous detection of mutations and copy number variation of NPM1 in the acute myeloid leukemia using multiplex ligation-dependent probe amplification. AB - The NPM1 gene encodes nucleophosmin, a protein involved in multiple cell functions and carcinogenesis. Mutation of the NPM1 gene, causing delocalization of the protein, is the most frequent genetic lesion in acute myeloid leukemia (AML); it is considered a founder event in AML pathogenesis and serves as a favorable prognostic marker. Moreover, in solid tumors and some leukemia cell lines, overexpression of the NPM1 gene is commonly observed. Therefore, the purpose of this study was to develop a new method for the detection of NPM1 mutations and the simultaneous analysis of copy number alterations (CNAs), which may underlie NPM1 gene expression deregulation. To address both of the issues, we applied a strategy based on multiplex ligation-dependent probe amplification (MLPA). A designed NPM1mut+ assay enables the detection of three of the most frequent NPM1 mutations: A, B and D. The accuracy of the assay was tested using a group of 83 samples from Polish patients with AML and other blood-proliferative disorders. To verify the results, we employed traditional Sanger sequencing and next-generation transcriptome sequencing. With the use of the NPM1mut+ assay, we detected mutations A, D and B in 14, 1 and 0 of the analyzed samples, respectively. All of these mutations were confirmed by complementary sequencing approaches, proving the 100% specificity and sensitivity of the proposed test. The performed sequencing analysis allowed the identification of two additional rare mutations (I and ZE). All of the mutations were identified exclusively in AML cases, accounting for 25% of those cases. We did not observe any CNAs (amplifications) of the NPM1 gene in the studied samples, either with or without the mutation. The presented method is simple, reliable and cost-effective. It can be easily introduced into clinical practice or developed to target both less frequent mutations in the NPM1 gene and other cancer-related genes. PMID- 26894558 TI - Synthesis of Mitomycin C and Decarbamoylmitomycin C N(2) deoxyguanosine-adducts. AB - Mitomycin C (MC) and Decarbamoylmitomycin C (DMC) - a derivative of MC lacking the carbamate on C10 - are DNA alkylating agents. Their cytotoxicity is attributed to their ability to generate DNA monoadducts as well as intrastrand and interstrand cross-links (ICLs). The major monoadducts generated by MC and DMC in tumor cells have opposite stereochemistry at carbon one of the guanine mitosene bond: trans (or alpha) for MC and cis (or beta) for DMC. We hypothesize that local disruptions of DNA structure from trans or cis adducts are responsible for the different biochemical responses produced by MC and DMC. Access to DNA substrates bearing cis and trans MC/DMC lesions is essential to verify this hypothesis. Synthetic oligonucleotides bearing trans lesions can be obtained by bio-mimetic methods. However, this approach does not yield cis adducts. This report presents the first chemical synthesis of a cis mitosene DNA adduct. We also examined the stereopreference exhibited by the two drugs at the mononucleotide level by analyzing the formation of cis and trans adducts in the reaction of deoxyguanosine with MC or DMC using a variety of activation conditions. In addition, we performed Density Functional Theory calculations to evaluate the energies of these reactions. Direct alkylation under autocatalytic or bifunctional conditions yielded preferentially alpha adducts with both MC and DMC. DFT calculations showed that under bifunctional activation, the thermodynamically favored adducts are alpha, trans, for MC and beta, cis, for DMC. This suggests that the duplex DNA structure may stabilize/oriente the activated pro-drugs so that, with DMC, formation of the thermodynamically favored beta products are possible in a cellular environment. PMID- 26894559 TI - Synthesis, alpha-glucosidase inhibitory, cytotoxicity and docking studies of 2 aryl-7-methylbenzimidazoles. AB - Benzimidazole analogs 1-27 were synthesized, characterized by EI-MS and (1)HNMR and their alpha-glucosidase inhibitory activities were found out experimentally. Compound 25, 19, 10 and 20 have best inhibitory activities with IC50 values 5.30+/-0.10, 16.10+/-0.10, 25.36+/-0.14 and 29.75+/-0.19 respectively against alpha-glucosidase. Compound 6 and 12 has no inhibitory activity against alpha glucosidase enzyme among the series. Further studies showed that the compounds are not showing any cytotoxicity effect. The docking studies of the compounds as well as the experimental activities of the compounds correlated well. From the molecular docking studies, it was observed that the top ranked conformation of all the compounds fit well in the active site of the homology model of alpha glucosidase. PMID- 26894560 TI - Alcohol and cannabis use among college students: Substitutes or complements? AB - AIMS: Economists debate whether changes in availability of alcohol or cannabis are positively or negatively related to changes in use of the other substance. Implicit in these arguments are two competing, individual-level hypotheses-that people use alcohol and cannabis either as complements or substitutes for one another. This is the first study to test these hypotheses using micro longitudinal data on individuals' alcohol and cannabis use on a given evening. METHODS: United States college students who use alcohol and cannabis (n=876) were selected from a larger sample who participated in a 30-day online daily diary study. At baseline, students reported their proclivity to use alcohol/drugs to cope with stress. Each day students reported their level of alcohol use from the prior evening as well as whether they had used cannabis. RESULTS: Evening levels of alcohol use and mean levels of alcohol use positively predicted the likelihood of evening cannabis use, results indicative of complementary use. This relation, however, was moderated by coping style, such that students who were more likely to use alcohol/drugs to cope were less likely to use cannabis as their evening or mean alcohol use levels increased, results indicative of substitution. CONCLUSIONS: Substance-using college students showed evidence for complementary alcohol and cannabis use at both the within- and between-person levels. Students with a proclivity toward using alcohol/drugs to cope, however, showed evidence of substitution. These findings suggest that studies based on economic theories of substance use should take into account individual differences in substance use motives. PMID- 26894561 TI - Social anxiety and alcohol-related impairment: The mediational impact of solitary drinking. AB - Social anxiety disorder more than quadruples the risk of developing an alcohol use disorder, yet it is inconsistently linked to drinking frequency. Inconsistent findings may be at least partially due to lack of attention to drinking context - it may be that socially anxious individuals are especially vulnerable to drinking more often in specific contexts that increase their risk for alcohol-related problems. For instance, socially anxious persons may drink more often while alone, before social situations for "liquid courage" and/or after social situations to manage negative thoughts about their performance. Among current (past-month) drinkers (N=776), social anxiety was significantly, positively related to solitary drinking frequency and was negatively related to social drinking frequency. Social anxiety was indirectly (via solitary drinking frequency) related to greater past-month drinking frequency and more drinking related problems. Social anxiety was also indirectly (via social drinking frequency) negatively related to past-month drinking frequency and drinking related problems. Findings suggest that socially anxious persons may be vulnerable to more frequent drinking in particular contexts (in this case alone) and that this context-specific drinking may play an important role in drinking problems among these high-risk individuals. PMID- 26894562 TI - Treatment of Mycobacterium tuberculosis-Infected Macrophages with Poly(Lactic-Co Glycolic Acid) Microparticles Drives NFkappaB and Autophagy Dependent Bacillary Killing. AB - The emergence of multiple-drug-resistant tuberculosis (MDR-TB) has pushed our available repertoire of anti-TB therapies to the limit of effectiveness. This has increased the urgency to develop novel treatment modalities, and inhalable microparticle (MP) formulations are a promising option to target the site of infection. We have engineered poly(lactic-co-glycolic acid) (PLGA) MPs which can carry a payload of anti-TB agents, and are successfully taken up by human alveolar macrophages. Even without a drug cargo, MPs can be potent immunogens; yet little is known about how they influence macrophage function in the setting of Mycobacterium tuberculosis (Mtb) infection. To address this issue we infected THP-1 macrophages with Mtb H37Ra or H37Rv and treated with MPs. In controlled experiments we saw a reproducible reduction in bacillary viability when THP-1 macrophages were treated with drug-free MPs. NFkappaB activity was increased in MP-treated macrophages, although cytokine secretion was unaltered. Confocal microscopy of immortalized murine bone marrow-derived macrophages expressing GFP tagged LC3 demonstrated induction of autophagy. Inhibition of caspases did not influence the MP-induced restriction of bacillary growth, however, blockade of NFkappaB or autophagy with pharmacological inhibitors reversed this MP effect on macrophage function. These data support harnessing inhaled PLGA MP-drug delivery systems as an immunotherapeutic in addition to serving as a vehicle for targeted drug delivery. Such "added value" could be exploited in the generation of inhaled vaccines as well as inhaled MDR-TB therapeutics when used as an adjunct to existing treatments. PMID- 26894564 TI - Comparison of biogas sludge and raw crop material as source of hydrolytic cultures for anaerobic digestion. AB - Mixed fermentative/hydrolytic bacteria were enriched on lignocellulose substrates in minimal medium under semi-anaerobic mesophilic conditions in the presence or absence of natural zeolite as growth supporter to ultimately bioaugment non adapted sludge and thereby enhance the overall anaerobic digestion (AD) of recalcitrant plant material. Desired enzyme activities, i.e. xylanases and cellulase were monitored during subsequent cultivation cycles. Furthermore, enriched microbial communities were characterized by 16S rRNA-based 454 Pyrosequencing, revealing Firmicutes, Bacteriodetes, Proteobacteria and Spirochaetes to be the predominant bacterial groups in cultures derived from anaerobic sludge and raw crop material, i.e. maple green cut and wheat straw as well. Enriched populations relevant for biopolymer hydrolysis were then compared in biological methane potential tests to demonstrate positive effects on the biogasification of renewable plant substrate material. A significant impact on methane productivity was observed with adapted mixed cultures when used in combination with clinoptilolite to augment and supplement non-adapted bioreactor sludge. PMID- 26894565 TI - Cultivation of Chlorella vulgaris in wastewater with waste glycerol: Strategies for improving nutrients removal and enhancing lipid production. AB - To improve nutrients removal from wastewater and enhance lipid production, cultivation of Chlorella vulgaris in wastewater with waste glycerol generated from biodiesel production using scum derived oil as feedstock was studied. The results showed that nutrients removal was improved and lipid production of C. vulgaris was enhanced with the addition of waste glycerol into wastewater to balance its C/N ratio. The optimal concentration of the pretreated glycerol for C. vulgaris was 10gL(-1) with biomass concentration of 2.92gL(-1), lipid productivity of 163mgL(-1)d(-1), and the removal of 100% ammonia and 95% of total nitrogen. Alkaline conditions prompted cell growth and lipid accumulation of C. vulgaris while stimulating nutrients removal. The application of the integration process can lower both wastewater treatment and biofuel feedstock costs. PMID- 26894563 TI - The rise of the starlet sea anemone Nematostella vectensis as a model system to investigate development and regeneration. AB - Reverse genetics and next-generation sequencing unlocked a new era in biology. It is now possible to identify an animal(s) with the unique biology most relevant to a particular question and rapidly generate tools to functionally dissect that biology. This review highlights the rise of one such novel model system, the starlet sea anemone Nematostella vectensis. Nematostella is a cnidarian (corals, jellyfish, hydras, sea anemones, etc.) animal that was originally targeted by EvoDevo researchers looking to identify a cnidarian animal to which the development of bilaterians (insects, worms, echinoderms, vertebrates, mollusks, etc.) could be compared. Studies in Nematostella have accomplished this goal and informed our understanding of the evolution of key bilaterian features. However, Nematostella is now going beyond its intended utility with potential as a model to better understand other areas such as regenerative biology, EcoDevo, or stress response. This review intends to highlight key EvoDevo insights from Nematostella that guide our understanding about the evolution of axial patterning mechanisms, mesoderm, and nervous systems in bilaterians, as well as to discuss briefly the potential of Nematostella as a model to better understand the relationship between development and regeneration. Lastly, the sum of research to date in Nematostella has generated a variety of tools that aided the rise of Nematostella to a viable model system. We provide a catalogue of current resources and techniques available to facilitate investigators interested in incorporating Nematostella into their research. WIREs Dev Biol 2016, 5:408-428. doi: 10.1002/wdev.222 For further resources related to this article, please visit the WIREs website. PMID- 26894566 TI - Effect of H2O2 concentrations on copper removal using the modified hydrothermal biochar. AB - This study investigated effect of H2O2 concentrations on copper removal using H2O2 modified hydrothermal carbonization Cymbopogon schoenanthus L. Spreng (HLG). Sorption behaviors of Cu (II) on the modified HLG by 20% H2O2 (mHLG2) could be the most desirable. Based on Langmuir isotherm, the maximum amount of Cu (II) uptake was in the sequence of mHLG2 (53.8mgg(-1))>mHLG1 (44.2mgg(-1))>mHLG3 (42.0mgg(-1))>mHLG0 (35.8mgg(-1)), which was higher than the results from majority of previous studies, suggesting that H2O2 modification advanced sorption capacity of hydrothermal biochars evidently. Effect mechanisms exploration indicated that the difference of Cu (II) removal by biochars before and after the modification was mainly related to functional groups. Carboxylic group was responsible for the best sorption property of Cu (II) by mHLG2, which was attributed to its significant relationships with H2O2 modification and Cu (II) removal. PMID- 26894567 TI - Breeding of high biomass and lipid producing Desmodesmus sp. by Ethylmethane sulfonate-induced mutation. AB - To improve the biomass yield and lipid productivity, two desert microalgae, Desmodesmus sp. S81 and G41 were induced mutagenesis by Ethylmethane sulfonate (EMS), and obtained two potential mutants, Desmodesmus sp. S5 and G3 from the mutagenic clones for their greatly promoted biomass and lipid production. The results showed that the biomass yield, lipid content and lipid productivity of the mutant strains S5 and G3 were 778.10mg.L(-1), 48.41% and 19.83mg.L(-1).d(-1), 739.52mg.L(-1), 46.01%, and 17.92mg.L(-1).d(-1), respectively, which presented the increment of 45.50%, 8.00% and 74.24%, 20.67%, 10.35% and 55.77% than those of S81 and G41. Comparing with the wild strains, the mutants showed reduced PUFAs and glycol lipids, elevated MUFAs and neutral lipids contents, which were appropriate for biodiesel production. PMID- 26894568 TI - Combustion characteristics and air pollutant formation during oxy-fuel co combustion of microalgae and lignite. AB - Oxy-fuel combustion of solid fuels is seen as one of the key technologies for carbon capture to reduce greenhouse gas emissions. The combustion characteristics of lignite coal, Chlorella vulgaris microalgae, and their blends under O2/N2 and O2/CO2 conditions were studied using a Thermogravimetric Analyzer-Mass Spectroscopy (TG-MS). During co-combustion of blends, three distinct peaks were observed and were attributed to C. vulgaris volatiles combustion, combustion of lignite, and combustion of microalgae char. Activation energy during combustion was calculated using iso-conventional method. Increasing the microalgae content in the blend resulted in an increase in activation energy for the blends combustion. The emissions of S- and N-species during blend fuel combustion were also investigated. The addition of microalgae to lignite during air combustion resulted in lower CO2, CO, and NO2 yields but enhanced NO, COS, and SO2 formation. During oxy-fuel co-combustion, the addition of microalgae to lignite enhanced the formation of gaseous species. PMID- 26894569 TI - Whole-Body Diffusion Imaging Applying Simultaneous Multi-Slice Excitation. PMID- 26894571 TI - Valorization of Olive Pomace Oil with Enzymatic Synthesis of 2-Monoacylglycerol. AB - 2-Monoacylglycerols (2-MAG) with a high content of oleic acid at sn-2 position was synthesized by enzymatic ethanolysis of refined olive pomace oil, which is a byproduct of olive oil processing. Six lipases from different microbial sources were used in the synthesis of 2-MAG. Immobilized lipase from Candida antarctica gave the highest product yield among the selected lipases. Response surface methodology was applied to optimize reaction conditions; time (4 to 10 h), temperature (45 to 60 degrees C), enzyme load (10 to 18 wt%), and ethanol:oil molar ratio (30:1 to 60:1). The predicted highest 2-MAG yield (84.83%) was obtained at 45 degrees C using 10 (wt%) enzyme load and 50:1 ethanol:oil molar ratio for 5 h reaction time. Experiments to confirm the predicted results at optimum conditions presented a 2-MAG yield of 82.54%. The purification yield (g 2 MAG extracted/100 g of total product) was 80.10 and 69.00 for solvent extraction and low-temperature crystallization, respectively. The purity of the synthesized 2-MAG was found to be higher than 96%. PMID- 26894570 TI - Developing a Time Series Predictive Model for Dengue in Zhongshan, China Based on Weather and Guangzhou Dengue Surveillance Data. AB - BACKGROUND: Dengue is a re-emerging infectious disease of humans, rapidly growing from endemic areas to dengue-free regions due to favorable conditions. In recent decades, Guangzhou has again suffered from several big outbreaks of dengue; as have its neighboring cities. This study aims to examine the impact of dengue epidemics in Guangzhou, China, and to develop a predictive model for Zhongshan based on local weather conditions and Guangzhou dengue surveillance information. METHODS: We obtained weekly dengue case data from 1st January, 2005 to 31st December, 2014 for Guangzhou and Zhongshan city from the Chinese National Disease Surveillance Reporting System. Meteorological data was collected from the Zhongshan Weather Bureau and demographic data was collected from the Zhongshan Statistical Bureau. A negative binomial regression model with a log link function was used to analyze the relationship between weekly dengue cases in Guangzhou and Zhongshan, controlling for meteorological factors. Cross-correlation functions were applied to identify the time lags of the effect of each weather factor on weekly dengue cases. Models were validated using receiver operating characteristic (ROC) curves and k-fold cross-validation. RESULTS: Our results showed that weekly dengue cases in Zhongshan were significantly associated with dengue cases in Guangzhou after the treatment of a 5 weeks prior moving average (Relative Risk (RR) = 2.016, 95% Confidence Interval (CI): 1.845-2.203), controlling for weather factors including minimum temperature, relative humidity, and rainfall. ROC curve analysis indicated our forecasting model performed well at different prediction thresholds, with 0.969 area under the receiver operating characteristic curve (AUC) for a threshold of 3 cases per week, 0.957 AUC for a threshold of 2 cases per week, and 0.938 AUC for a threshold of 1 case per week. Models established during k-fold cross-validation also had considerable AUC (average 0.938-0.967). The sensitivity and specificity obtained from k-fold cross validation was 78.83% and 92.48% respectively, with a forecasting threshold of 3 cases per week; 91.17% and 91.39%, with a threshold of 2 cases; and 85.16% and 87.25% with a threshold of 1 case. The out-of-sample prediction for the epidemics in 2014 also showed satisfactory performance. CONCLUSION: Our study findings suggest that the occurrence of dengue outbreaks in Guangzhou could impact dengue outbreaks in Zhongshan under suitable weather conditions. Future studies should focus on developing integrated early warning systems for dengue transmission including local weather and human movement. PMID- 26894572 TI - Metformin effectiveness and safety in the management of overweight/obese nondiabetic children and adolescents: metabolic benefits of the continuous exposure to metformin at 12 and 24 months. AB - INTRODUCTION: Childhood obesity prevalence is rising and new therapeutical approaches are needed. Metformin is likely beneficial in obese and/or insulin resistant children/adolescents, but its role in this setting is still unclear. We aimed to evaluate the effectiveness, in terms of weight loss and insulin resistance, and safety of metformin in nondiabetic overweight/obese children and adolescents. METHODS: We retrospectively reviewed clinical records of 78 nondiabetic obese/overweight [body mass index (BMI)>=85th/95th percentile for age and sex] children and adolescents. Anthropometric and metabolic outcomes of 39 patients treated with metformin (mean daily dose: 1.3+/-0.5 g) were analyzed and compared to lifestyle intervention alone at different follow-up times (12 and 24 months). RESULTS: The mean age of the 78 patients was 13.3 years, 41 were females and mean BMI and BMI-SDS were 32.8 kg/m2 and 3.1, respectively. There was a decrease in mean BMI-SDS within each treatment group in all periods, except at 24 months for lifestyle intervention. However, the change in BMI-SDS was not significantly superior in the metformin group when compared to lifestyle intervention. Metformin had greater effectiveness over lifestyle intervention alone in reducing fasting insulin levels and homeostasis model assessment for insulin-resistance index (HOMA-IR) at both 12 and 24 months. Five patients had gastrointestinal adverse effects (12.8%), four requiring dose reduction, but metformin could be resumed in all. CONCLUSION: Metformin for nondiabetic obese/overweight children and adolescents resulted in a noteworthy insulin resistance improvement, without significant BMI advantage when compared to lifestyle intervention. Metformin metabolic and anthropometric effects appear to be beneficial up to 24 months, without relevant adverse effects, highlighting its potential long-term benefits. PMID- 26894573 TI - Congenital hypothyroidism and thyroid dyshormonogenesis: a case report of siblings with a newly identified mutation in thyroperoxidase. AB - BACKGROUND: Thyroid dyshormonogenesis continues to be a significant cause of congenital hypothyroidism. Over time, forms of thyroid dyshormonogenesis can result in goiter, which can lead to difficult management decisions as the pathologic changes can both mimic or lead to thyroid cancer. METHODS: Herein we describe the cases of two brothers diagnosed with congenital hypothyroidism, with initial findings consistent with thyroid dyshormonogenesis. One brother eventually developed multinodular goiter with complex pathology on biopsy, resulting in thyroidectomy. RESULTS: Whole exome sequencing revealed the brothers carry a novel frameshift mutation in thyroperoxidase; the mutation, while not previously described, was likely both deleterious and pathogenic. Conlcusions: These cases highlight the complex pathology that can occur within thyroid dyshormonogenesis, with similar appearance to possible thyroid cancer, leading to complex management decisions. They also highlight the role that a genetic diagnosis can play in interpreting the impact of dyshormonogenesis on nodular thyroid development, and the need for long-term follow-up in these patients. PMID- 26894574 TI - Improved molecular diagnosis of patients with neonatal diabetes using a combined next-generation sequencing and MS-MLPA approach. AB - BACKGROUND: We evaluated a methylation-specific multiplex-ligation-dependent probe amplification (MS-MLPA) assay for the molecular diagnosis of transient neonatal diabetes mellitus (TNDM) caused by 6q24 abnormalities and assessed the clinical utility of using this assay in combination with next generation sequencing (NGS) analysis for diagnosing patients with neonatal diabetes (NDM). METHODS: We performed MS-MLPA in 18 control samples and 42 retrospective NDM cases with normal bi-parental inheritance of chromosome 6. Next, we evaluated 22 prospective patients by combining NGS analysis of 11 NDM genes and the MS-MLPA assay. RESULTS: 6q24 aberrations were identified in all controls and in 19% of patients with normal bi-parental inheritance of chromosome 6. The MS-MLPA/NGS combined approach identified a genetic cause in ~64% of patients with NDM of unknown etiology. CONCLUSIONS: MS-MLPA is a reliable method to identify all known 6q24 abnormalities and comprehensive testing of all causes reveals a causal mutation in ~64% of patients. PMID- 26894575 TI - De novo mutation of PHEX in a type 1 diabetes patient. AB - A new missense mutation on the X chromosome (PHEX) at exon 4(c.442C>T) in a 4 generation Chinese Han pedigree is reported. The proband and four family members were clinically identified as the X-linked hypophosphatemic rickets (XLH) which is a dominant inherited disorder characterized by renal phosphate wasting, aberrant vitamin D metabolism, and abnormal bone mineralization. The proband is identified as hemizygous with the four female family members to be heterozygous genotypes. The discovery was made through the complete sequencing of the exons and the intron-exon boundaries of the PHEX gene of this family. The mutation caused the S141 residue to change to Phe from Ser which is perfectly conserved among humans, mice, rats, cows and chickens. PolyPhen-2 software analysis of the mutation indicated it was probably damaging. The proband was also diagnosed with type 1 diabetes (T1D) and the relationship between XLH and diabetes phenotypes was discussed in the paper. PMID- 26894576 TI - Neuroprotective effect of Decalepis hamiltonii on cyclophosphamide-induced oxidative stress in the mouse brain. AB - BACKGROUND: Cyclophosphamide (CP), one of the most widely used antineoplastic drugs, causes toxic side effects on vital organs including brain. In this study, we have investigated neuroprotective potential of the aqueous extract of the roots of Decalepis hamiltonii (DHA) against CP-induced oxidative stress in the mouse brain. METHODS: Swiss albino male mice were pre-treated with DHA (50 and 100 mg/kg b.w.) for 10 consecutive days followed by an injection with CP intraperitoneally (25 mg/kg b.w.) for 10 days 1 h after DHA treatment; 16 h later, they were euthanized, their brains were immediately removed, and biochemical and molecular analyses were conducted. RESULTS: The results indicated that injection of CP induced oxidative stress in the mouse brain as evident from the increased lipid peroxidation, reactive oxygen species, depletion of glutathione and reduced activities of the antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione-S-transferase. Treatment with DHA significantly mitigated the CP induced oxidative stress. Moreover, expression of genes for the antioxidant enzymes was downregulated by CP treatment which was reversed by DHA. CONCLUSIONS: In conclusion, DHA protected the brain from oxidative stress induced by CP, and therefore, it could be a promising nutraceutical as a supplement in cancer chemotherapy in order to ameliorate the toxic side effects of cancer drugs. PMID- 26894577 TI - Identification of protein phosphatase 2A as an interacting protein of leucine rich repeat kinase 2. AB - Mutations in the gene coding for the multi-domain protein leucine-rich repeat kinase 2 (LRRK2) are the leading cause of genetically inherited Parkinson's disease (PD). Two of the common found mutations are the R1441C and G2019S. In this study we identified protein phosphatase 2A (PP2A) as an interacting partner of LRRK2. We were able to demonstrate that the Ras of complex protein (ROC) domain is sufficient to interact with the three subunits of PP2A in human neuroblastoma SH-SY5Y cells and in HeLa cells. The alpha subunit of PP2A is interacting with LRRK2 in the perinuclear region of HeLa cells. Silencing the catalytic subunit of PP2A by shRNA aggravated cellular degeneration induced by the pathogenic R1441C-LRRK2 mutant expressed in neuroblastoma SH-SY5Y cells. A similar enhancement of apoptotic nuclei was observed by downregulation of the catalytic subunit of PP2A in cultured cortical cells derived from neurons overexpressing the pathogenic mutant G2019S-LRRK2. Conversely, pharmacological activation of PP2A by sodium selenate showed a partial neuroprotection from R1441C-LRRK2-induced cellular degeneration. All these data suggest that PP2A is a new interacting partner of LRRK2 and reveal the importance of PP2A as a potential therapeutic target in PD. PMID- 26894578 TI - Exploring the active site binding specificity of kallikrein-related peptidase 5 (KLK5) guides the design of new peptide substrates and inhibitors. AB - Kallikrein-related peptidase 5 (KLK5) is a promising therapeutic target in several skin diseases, including Netherton syndrome, and is emerging as a potential target in various cancers. In this study, we used a sparse matrix library of 125 individually synthesized peptide substrates to characterize the binding specificity of KLK5. The sequences most favored by KLK5 were GRSR, YRSR and GRNR, and we identified sequence-specific interactions involving the peptide N-terminus by analyzing kinetic constants (kcat and KM) and performing molecular dynamics simulations. KLK5 inhibitors were subsequently engineered by substituting substrate sequences into the binding loop (P1, P2 and P4 residues) of sunflower trypsin inhibitor-1 (SFTI-1). These inhibitors were effective against KLK5 but showed limited selectivity, and performing a further substitution at P2' led to the design of a new variant that displayed improved activity against KLK5 (Ki=4.2+/-0.2 nm), weak activity against KLK7 and 12-fold selectivity over KLK14. Collectively, these findings provide new insight into the design of highly favored binding sequences for KLK5 and reveal several opportunities for modulating inhibitor selectivity over closely related proteases that will be useful for future studies aiming to develop therapeutic molecules targeting KLK5. PMID- 26894579 TI - Differences in lupus anticoagulant final conclusion through clotting time or Rosner index for mixing test interpretation. AB - BACKGROUND: Lupus anticoagulant (LAC) testing includes a screening, mixing and confirmation step. Although recently published guidelines on LAC testing are a useful step towards standardization, a lack of consensus remains whether to express mixing tests in clotting time (CT) or index of circulating anticoagulant (ICA). The influence of anticoagulant therapy, e.g. vitamin K antagonists (VKA) or direct oral anticoagulants (DOAC) on both methods of interpretation remains to be investigated. The objective of this study was to contribute to a simplification and standardization of the LAC three-step interpretation on the level of the mixing test. METHODS: Samples from 148 consecutive patients with LAC request and prolonged screening step, and 77 samples from patients non-suspicious for LAC treated with VKA (n=37) or DOAC (n=30) were retrospectively evaluated. An activated partial thromboplastin time (aPTT) and dilute Russell's viper venom time (dRVVT) were used for routine LAC testing. The supplemental anticoagulant samples were tested with dRVVT only. We focused on the interpretation differences for mixing tests expressed as CT or ICA and compared the final LAC conclusion within each distinct group of concordant and discordant mixing test results. RESULTS: Mixing test interpretation by CT resulted in 10 (dRVVT) and 16 (aPTT) more LAC positive patients compared to interpretation with ICA. Isolated prolonged dRVVT screen mix ICA results were exclusively observed in samples from VKA-treated patients without suspicion for LAC. CONCLUSIONS: We recommend using CT in respect to the 99th percentile cut-off for interpretation of mixing steps in order to reach the highest sensitivity and specificity in LAC detection. PMID- 26894580 TI - SLC26A4 genotypes associated with enlarged vestibular aqueduct malformation in south Italian children with sensorineural hearing loss. PMID- 26894581 TI - Serum 25-Hydroxyvitamin D Levels and Dry Eye Syndrome: Differential Effects of Vitamin D on Ocular Diseases. AB - PURPOSE: To investigate associations between serum 25-hydroxyvitamin D levels and dry eye syndrome (DES), and to evaluate the differential effect of vitamin D on ocular diseases including age-related macular disease (AMD), diabetic retinopathy (DR), cataract, and DES. METHODS: A total of 16,396 participants aged >19 years were randomly selected from the Korean National Health and Nutrition Examination Survey. All participants participated in standardized interviews, blood 25 hydroxyvitamin D level evaluations, and comprehensive ophthalmic examinations. DES was defined by a history of clinical diagnosis of dry eyes by a physician. The association between vitamin D and DES was compared to the associations between vitamin D and AMD, DR, cataract, and DES from our previous studies. RESULTS: The odds of DES non-significantly decreased as the quintiles of serum 25 hydroxyvitamin D levels increased (quintile 5 versus 1, OR = 0.85, 95%CI: 0.55 1.30, P for trend = 0.076) after adjusting for potential confounders including age, sex, hypertension, diabetes, smoking status, and sunlight exposure times. The relative odds of DES (OR = 0.70, 95% CI: 0.30-1.64) and cataract (OR = 0.76, 95% CI: 0.59-0.99) were relatively high, while those of DR (OR = 0.37, 95% CI: 0.18-0.76) and late AMD (OR = 0.32, 95% CI: 0.12-0.81) were lower in men. CONCLUSIONS: The present study does not support an association between serum 25 hydroxyvitamin D levels and DES. The preventive effect of serum 25-hydroxyvitamin D may be more effective for DR and late AMD than it is for cataract and DES. PMID- 26894582 TI - Association of Vitamin D Receptor Polymorphism with Susceptibility to Symptomatic Pertussis. AB - Pertussis, caused by infection with the gram negative B. pertussis bacterium, is a serious respiratory illness that can last for months. While B. pertussis infection rates are estimated between 1-10% in the general population, notifications of symptomatic pertussis only comprise 0.01-0.1% indicating that most individuals clear B. pertussis infections without developing (severe) clinical symptoms. In this study we investigated whether genetic risk factors are involved in the development of symptomatic pertussis upon B. pertussis infection. Single-nucleotide polymorphisms (SNPs) in candidate genes, MBL2, IL17A, TNFalpha, VDR, and IL10 were genotyped in a unique Dutch cohort of symptomatic clinically confirmed (ex-)pertussis patients and in a Dutch population cohort. Of the seven investigated SNPs in five genes, a polymorphism in the Vitamin D receptor (VDR) gene (rs10735810) was associated with pertussis. The VDR major allele and its homozygous genotype were more present in the symptomatic pertussis patient cohort compared to the control population cohort. Interestingly, the VDR major allele correlated also with the duration of reported pertussis symptoms. Vitamin D3 (VD3) and VDR are important regulators of immune activation. Altogether, these findings suggest that polymorphisms in the VDR gene may affect immune activation and the clinical outcome of B. pertussis infection. PMID- 26894584 TI - Correction: Gateway Vectors for Efficient Artificial Gene Assembly In Vitro and Expression in Yeast Saccharomyces cerevisiae. PMID- 26894583 TI - Differential Juvenile Hormone Variations in Scale Insect Extreme Sexual Dimorphism. AB - Scale insects have evolved extreme sexual dimorphism, as demonstrated by sedentary juvenile-like females and ephemeral winged males. This dimorphism is established during the post-embryonic development; however, the underlying regulatory mechanisms have not yet been examined. We herein assessed the role of juvenile hormone (JH) on the diverging developmental pathways occurring in the male and female Japanese mealybug Planococcus kraunhiae (Kuwana). We provide, for the first time, detailed gene expression profiles related to JH signaling in scale insects. Prior to adult emergence, the transcript levels of JH acid O methyltransferase, encoding a rate-limiting enzyme in JH biosynthesis, were higher in males than in females, suggesting that JH levels are higher in males. Furthermore, male quiescent pupal-like stages were associated with higher transcript levels of the JH receptor gene, Methoprene-tolerant and its co activator taiman, as well as the JH early-response genes, Kruppel homolog 1 and broad. The exposure of male juveniles to an ectopic JH mimic prolonged the expression of Kruppel homolog 1 and broad, and delayed adult emergence by producing a supernumeral pupal stage. We propose that male wing development is first induced by up-regulated JH signaling compared to female expression pattern, but a decrease at the end of the prepupal stage is necessary for adult emergence, as evidenced by the JH mimic treatments. Furthermore, wing development seems linked to JH titers as JHM treatments on the pupal stage led to wing deformation. The female pedomorphic appearance was not reflected by the maintenance of high levels of JH. The results in this study suggest that differential variations in JH signaling may be responsible for sex-specific and radically different modes of metamorphosis. PMID- 26894585 TI - Ruthenium-Catalyzed, Site-Selective C-H Allylation of Indoles with Allyl Alcohols as Coupling Partners. AB - A new ruthenium-catalyzed, heteroatom-directed strategy for C-H allylation of indoles is described. The use of allyl alcohols as coupling partners as well as pyridine as the removable directing group is highlighted. This methodology provides access to C2-allylated indoles by utilizing a strategy that does not require prefunctionalization of either of the coupling partners. PMID- 26894586 TI - National Clinical Skills Competition: an effective simulation-based method to improve undergraduate medical education in China. AB - BACKGROUND: The National Clinical Skills Competition has been held in China for 5 consecutive years since 2010 to promote undergraduate education reform and improve the teaching quality. The effects of the simulation-based competition will be analyzed in this study. METHODS: Participation in the competitions and the compilation of the questions used in the competition finals are summarized, and the influence and guidance quality are further analyzed. Through the nationwide distribution of questionnaires in medical colleges, the effects of the simulation-based competition on promoting undergraduate medical education reform were evaluated. RESULTS: The results show that approximately 450 students from more than 110 colleges (accounting for 81% of colleges providing undergraduate clinical medical education in China) participated in the competition each year. The knowledge, skills, and attitudes were comprehensively evaluated by simulation based assessment. Eight hundred and eighty copies of the questionnaires were distributed to 110 participating medical schools in 2015. In total, 752 valid responses were received across 95 schools. The majority of the interviewees agreed or strongly agreed that competition promoted the adoption of advanced educational principles (76.8%), updated the curriculum model and instructional methods (79.8%), strengthened faculty development (84.0%), improved educational resources (82.1%), and benefited all students (53.4%). CONCLUSIONS: The National Clinical Skills Competition is widely accepted in China. It has effectively promoted the reform and development of undergraduate medical education in China. PMID- 26894587 TI - Innovative integrative bedside teaching model improves tutors' self-assessments of teaching skills and attitudes. AB - INTRODUCTION: Patient bedside is the ideal setting for teaching physical examination, medical interviewing, and interpersonal skills. Herein we describe a novel model for bedside teaching (BST) practiced during tutor training workshop and its resulting effect on practitioners' self assessment of teaching skills and perceptions. METHODS: One-day tutor training workshop included theoretical knowledge supplementation regarding tutors' roles as well as implementing practical tools for clinical education, mainly BST model. The model, which emphasizes simultaneous clinical and communication teaching in a stepwise approach, was practiced by consecutive simulations with a gradual escalation of difficulty and adjusted instruction approaches. Pre- and post-workshop-adjusted questionnaires using a Likert scale of 1 to 4 were completed by participants and compared. RESULTS: Analysis was based on 25 out of 48 participants who completed both questionnaires. Significantly improved teaching skills were demonstrated upon workshop completion (mean 3.3, SD 0.5) compared with pre-training (mean 2.6, SD 0.6; p<0.001) with significant increase in most examined parameters. Significantly improved tutor's roles internalization was demonstrated after training completion (mean 3.7, SD 0.3) compared with pre-workshop (mean 3.5 SD 0.5; p=0.002). DISCUSSION: Successful BST involves combination of clinical and communication skills. BST model practiced during the workshop may contribute to improved teaching skills in this challenging environment. PMID- 26894588 TI - Avocado waste for finishing pigs: Impact on muscle composition and oxidative stability during chilled storage. AB - The utilization of agricultural waste materials for pig feeding may be an interesting option for reducing production costs and contributing to sustainability and environmental welfare. In the present study, a mixed diet enriched with avocado waste (TREATED) is used for finishing industrial genotype pigs. The muscle longissimus thoracis et lomborum (LTL) from TREATED pigs was analyzed for composition and oxidative and color stability and compared with muscles obtained from pigs fed a CONTROL diet. Dietary avocado had significant impact on the content and composition of intramuscular fat (IMF), reducing the lipid content in LTL muscles and increasing the degree of unsaturation. This did not increase the oxidative instability of samples. On the contrary, muscles from TREATED pigs had significantly lower lipid and protein oxidation rates during chilled storage. The color of the muscles from TREATED pigs was also preserved from oxidation. PMID- 26894590 TI - Granzymes A and B Regulate the Local Inflammatory Response during Klebsiella pneumoniae Pneumonia. AB - Klebsiella pneumoniae is a common cause of hospital-acquired pneumonia. Granzymes (gzms), mainly found in cytotoxic lymphocytes, have been implicated as mediators of infection and inflammation. We here sought to investigate the role of gzmA and gzmB in the host response to K. pneumoniae-induced airway infection and sepsis. For this purpose, pneumonia was induced in wild-type (WT) and gzmA-deficient (gzmA-/-), gzmB-/- and gzmAxB-/- mice by intranasal infection with K. pneumoniae. In WT mice, gzmA and gzmB were mainly expressed by natural killer cells. Pneumonia was associated with reduced intracellular gzmA and increased intracellular gzmB levels. Gzm deficiency had little impact on antibacterial defence: gzmA-/- and gzmAxB-/- mice transiently showed modestly higher bacterial loads in the lungs but not in distant organs. GzmB-/- and, to a larger extent, gzmAxB-/- mice displayed transiently increased lung inflammation, reflected in the semi-quantitative histology scores and levels of pro-inflammatory cytokines and chemokines. Most differences between gzm-deficient and WT mice had disappeared during late-stage pneumonia. Gzm deficiency did not impact on distant organ injury or survival. These results suggest that gzmA and gzmB partly regulate local inflammation during early pneumonia but eventually play an insignificant role during pneumosepsis by the common human pathogen K. pneumoniae. PMID- 26894589 TI - Ret and Etv4 Promote Directed Movements of Progenitor Cells during Renal Branching Morphogenesis. AB - Branching morphogenesis of the epithelial ureteric bud forms the renal collecting duct system and is critical for normal nephron number, while low nephron number is implicated in hypertension and renal disease. Ureteric bud growth and branching requires GDNF signaling from the surrounding mesenchyme to cells at the ureteric bud tips, via the Ret receptor tyrosine kinase and coreceptor Gfralpha1; Ret signaling up-regulates transcription factors Etv4 and Etv5, which are also critical for branching. Despite extensive knowledge of the genetic control of these events, it is not understood, at the cellular level, how renal branching morphogenesis is achieved or how Ret signaling influences epithelial cell behaviors to promote this process. Analysis of chimeric embryos previously suggested a role for Ret signaling in promoting cell rearrangements in the nephric duct, but this method was unsuited to study individual cell behaviors during ureteric bud branching. Here, we use Mosaic Analysis with Double Markers (MADM), combined with organ culture and time-lapse imaging, to trace the movements and divisions of individual ureteric bud tip cells. We first examine wild-type clones and then Ret or Etv4 mutant/wild-type clones in which the mutant and wild-type sister cells are differentially and heritably marked by green and red fluorescent proteins. We find that, in normal kidneys, most individual tip cells behave as self-renewing progenitors, some of whose progeny remain at the tips while others populate the growing UB trunks. In Ret or Etv4 MADM clones, the wild-type cells generated at a UB tip are much more likely to remain at, or move to, the new tips during branching and elongation, while their Ret-/- or Etv4-/- sister cells tend to lag behind and contribute only to the trunks. By tracking successive mitoses in a cell lineage, we find that Ret signaling has little effect on proliferation, in contrast to its effects on cell movement. Our results show that Ret/Etv4 signaling promotes directed cell movements in the ureteric bud tips, and suggest a model in which these cell movements mediate branching morphogenesis. PMID- 26894591 TI - Sugammadex at both high and low doses does not affect the depth of anesthesia or hemodynamics: a randomized double blind trial. AB - Previous studies have shown that sugammadex decreases the anesthetic depth when administered to reverse the neuromuscular blockade produced by rocuronium/vecuronium. The aim of the present study was to investigate the effect of sugammadex alone on anesthetic depth and hemodynamics. Sixty patients scheduled for abdominal surgery participated in the study. Anesthesia was induced with thiopental/fentanyl and maintained with N2O/oxygen and sevoflurane concentrations adjusted to maintain Entropy and Bispectral Index (BIS) values between 40 and 50. Cis-atracurium 0.2 mg/kg was administered for neuromuscular blockade which was monitored with a TOF-Watch(r) SX acceleromyograph. State entropy (SE), response entropy (RE), Bispectral Index (BIS), systolic (SAP) and diastolic blood pressure (DAP), heart rate (HR), SpO2, end-tidal CO2 and sevoflurane concentrations were recorded every 3 min intraoperatively. Sugammadex 2 mg/kg (Group-2), 4 mg/kg (Group-4) or 16 mg/kg (Group-16) was given intravenously when a count of two responses of the train-of-four (TOF) or a post tetanic count (PTC) 1-3 appeared or when no response at all (PTC = 0) was observed, respectively. The overall SE values, thus the primary outcome of the study, were 44 +/- 11, 43 +/- 10 and 43 +/- 11 for Group-2, Group-4 and Group-16, respectively (p = 0.812). Also, the secondary endpoints, namely RE, BIS, SAP and DAP, HR and SpO2 did not differ between the three groups. Comparisons between Group-2 versus Group-4, Group-2 versus Group-16 and Group-4 versus Group-16 showed no differences (p > 0.05) for all the studied variables. Sugammadex alone at low, medium or high clinical doses has no effect on anesthetic depth as assessed by Entropy and BIS or on hemodynamics. PMID- 26894592 TI - A risk stratification algorithm using non-invasive respiratory volume monitoring to improve safety when using post-operative opioids in the PACU. AB - Late detection of respiratory depression in non-intubated patients compromises patient safety. SpO2 is a lagging indicator of respiratory depression and EtCO2 has proven to be unreliable in non-intubated patients. A decline in minute ventilation (MV) is the earliest sign of respiratory depression. A non-invasive respiratory volume monitor (RVM) that provides accurate, continuous MV measurements enables clinicians to predict and quantify respiratory compromise. For this observational study, practitioners were blinded to the RVM measurements and pain management followed the usual routine. Patients were stratified by their MV on PACU admission and classified as "At-Risk" or "Not-At-Risk," with progression to "Low MV" status following opioids assessed for each category. The purpose was to determine if stratifying based on MV on PACU arrival could identify patients at higher risk for respiratory depression. Ability to identify in advance patients at higher risk for respiratory depression following standard opioid dosing would drive changes in pain management and improve patient care. RVM and opioid administration data from 150 PACU patients following elective joint-replacement surgery were collected in an observational study. "Predicted" MV (MVPRED) and "Percent Predicted" (MVMEASURED/MVPRED * 100 %) were calculated for each patient using standard formulas. Prior to opioid administration, patients were classified as either "Not-At-Risk" (MV >= 80 % MVPRED) or "At-Risk" (MV < 80 % MVPRED). "Low MV" was defined as MV < 40 % MVPRED. Post-operative apnea (POA) was defined as >=5 ten-second apneas per hour of PACU stay. We compared the incidences of Low MV following a single opioid dose, POA, and Low MV at discharge for both groups. In the PACU, 74/150 patients received opioids. Within 15 min of opioid administration, 32 % (24/74) developed Low MV. The risk stratification algorithm identified 22/24 patients (92 % sensitivity). Only 46 % of them had POA, and the majority had Low MV without POA. At discharge, 29/150 patients had Low MV and those receiving opioids were 50 % more likely to display Low MV (23 vs. 16 %). The RVM can identify patients at-risk for opioid-induced respiratory depression and/or experiencing POA. Monitoring of MV can guide opioid dosing regimens and may increase patient safety across the continuum of care. PMID- 26894593 TI - Nanomechanical Contribution of Collagen and von Willebrand Factor A in Marine Underwater Adhesion and Its Implication for Collagen Manipulation. AB - Recent works on mussel adhesion have identified a load bearing matrix protein (PTMP1) containing von Willebrand factor (vWF) with collagen binding capability that contributes to the mussel holdfast by manipulating mussel collagens. Using a surface forces apparatus, we investigate for the first time, the nanomechanical properties of vWF-collagen interaction using homologous proteins of mussel byssus, PTMP1 and preCollagens (preCols), as collagen. Mimicking conditions similar to mussel byssus secretion (pH < 5.0) and seawater condition (pH 8.0), PTMP1 and preCol interact weakly in the "positioning" phase based on vWF-collagen binding and strengthen in "locked" phase due to the combined effects of electrostatic attraction, metal binding, and mechanical shearing. The progressive enhancement of binding between PTMP1 with porcine collagen under the aforementioned conditions is also observed. The binding mechanisms of PTMP1 preCols provide insights into the molecular interaction of the mammalian collagen system and the development of an artificial extracellular matrix based on collagens. PMID- 26894595 TI - Fully automated classification of bone marrow infiltration in low-dose CT of patients with multiple myeloma based on probabilistic density model and supervised learning. AB - This paper presents a fully automated method for the identification of bone marrow infiltration in femurs in low-dose CT of patients with multiple myeloma. We automatically find the femurs and the bone marrow within them. In the next step, we create a probabilistic, spatially dependent density model of normal tissue. At test time, we detect unexpectedly high density voxels which may be related to bone marrow infiltration, as outliers to this model. Based on a set of global, aggregated features representing all detections from one femur, we classify the subjects as being either healthy or not. This method was validated on a dataset of 127 subjects with ground truth created from a consensus of two expert radiologists, obtaining an AUC of 0.996 for the task of distinguishing healthy controls and patients with bone marrow infiltration. To the best of our knowledge, no other automatic image-based method for this task has been published before. PMID- 26894594 TI - Host-virus interactions in hepatitis B and hepatitis C infection. AB - Hepatitis B virus (HBV) and hepatitis C virus (HCV) are among the most endemic pathogens worldwide, with more than 500 million people globally currently infected with these viruses. These pathogens can cause acute and chronic hepatitis that progress to liver cirrhosis or hepatocellular carcinoma. Both viruses utilize multifaceted strategies to evade the host surveillance system and fall below the immunological radar. HBV has developed specific strategies to evade recognition by the innate immune system and is acknowledged to be a stealth virus. However, extensive research has revealed that HBV is recognized by dendritic cells (DCs) and natural killer (NK) cells. Indoleamine-2, 3-dioxygenase is an enforcer of sequential immune reactions in acute hepatitis B, and this molecule has been shown to be induced by the interaction of HBV-infected hepatocytes, DCs, and NK cells. The interleukin-28B genotype has been reported to influence HCV eradication either therapeutically or spontaneously, but the biological function of its gene product, a type-III interferon (IFN-lambda3), remains to be elucidated. Human BDCA3(+)DCs have also been shown to be a potent producer of IFN-lambda3 in HCV infection, suggesting the possibility that BDCA3(+)DCs could play a key role in developing therapeutic HCV vaccine. Here we review the current state of research on immune responses against HBV and HCV infection, with a specific focus on innate immunity. A comprehensive study based on clinical samples is urgently needed to improve our understanding of the immune mechanisms associated with viral control and thus to develop novel immune modulatory therapies to cure chronic HBV and HCV infection. PMID- 26894596 TI - Automated retinal image quality assessment on the UK Biobank dataset for epidemiological studies. AB - Morphological changes in the retinal vascular network are associated with future risk of many systemic and vascular diseases. However, uncertainty over the presence and nature of some of these associations exists. Analysis of data from large population based studies will help to resolve these uncertainties. The QUARTZ (QUantitative Analysis of Retinal vessel Topology and siZe) retinal image analysis system allows automated processing of large numbers of retinal images. However, an image quality assessment module is needed to achieve full automation. In this paper, we propose such an algorithm, which uses the segmented vessel map to determine the suitability of retinal images for use in the creation of vessel morphometric data suitable for epidemiological studies. This includes an effective 3-dimensional feature set and support vector machine classification. A random subset of 800 retinal images from UK Biobank (a large prospective study of 500,000 middle aged adults; where 68,151 underwent retinal imaging) was used to examine the performance of the image quality algorithm. The algorithm achieved a sensitivity of 95.33% and a specificity of 91.13% for the detection of inadequate images. The strong performance of this image quality algorithm will make rapid automated analysis of vascular morphometry feasible on the entire UK Biobank dataset (and other large retinal datasets), with minimal operator involvement, and at low cost. PMID- 26894598 TI - Digitally Analyzed Conjunctival Redness: Does Repeated Conjunctival Provocation Intrinsically Cause Local Desensitization of the Eye? AB - BACKGROUND: Allergic reactions in patients with seasonal or perennial rhinoconjunctivitis mediated by airborne allergens can be effectively assessed with the conjunctival provocation test (CPT). The CPT is a fast and easy diagnostic procedure that challenges the ocular mucosa with instillations of allergen solutions into the conjunctival region. This paper aimed to investigate the possible influence of repeated diagnostic CPT procedures on the patient's clinical presentation, i.e. to analyze desensitization effects caused by diagnostic solutions and to show the reproducibility of CPT results. METHODS: Treatment progress in 120 placebo-treated patients from 2 immunotherapeutic dose finding studies was estimated and documented, as based on the CPT which was applied at 4 visits with intervals of 4, 8 and 16 weeks. High-resolution digital photos collected as part of the CPT documentation were analyzed by an external observer and by digital analysis software to determine conjunctival redness, completely independent of the subjectivity of investigators and patients. RESULTS: Two extremal scenarios of the redness changes were considered after provocation with 10,000 standard quality units/ml. A maximal decrease of about 3% (t test: p = 0.0002; U test: p = 0.001) and a minimal decrease of about 1% (t test: p = 0.254; U test: p = 0.431) were found. CONCLUSIONS: The observed decrease in conjunctival hyperemia can be explained by local desensitization or by placebo effect. Due to the setup of both studies considered, we could not ascertain how these factors influence the decrease in redness. In order to attribute the observed effects to local conjunctival desensitization with certainty, further pilot studies are needed. PMID- 26894599 TI - Radical Pair-Driven Luminescence of Quantum Dots for Specific Detection of Peroxynitrite in Living Cells. AB - There is currently great interest in developing chemiluminescence (CL) probes that can selectively detect peroxynitrite (ONOO(-)) in living cells. In comparison with other reactive oxygen species (ROS), ONOO(-) can spontaneously decompose into a series of radicals. Notably, the interaction of quantum dots (QDs) with oxidizing/reducing ROS radicals can generate a strong CL emission by electron-transfer annihilation. Herein, we report a novel CL probe that affords the ability to distinguish ONOO(-) from other ROS in living cells. ONOO(-) can activate luminescence of QDs in the absence of excitation source, effectively avoiding background noise and scattering of light from biological matrixes produced by in situ excitation; however, there is no response to other ROS including (1)O2, H2O2, (*)OH, O2(*-), and ClO(-). The outstanding selectivity of the present CL probe leads us to detect the exogenous release of ONOO(-) from 3 morpholinosydnonimine (SIN-1) in living cells. These results suggest that this present probe-based CL provides a promising platform for highly selective and sensitive detection of ONOO(-) in biological systems. PMID- 26894597 TI - Hypoxia-Inducible Factor Stabilizers: a New Avenue for Reducing BP While Helping Hemoglobin? AB - Anemia of chronic kidney disease (CKD) is common and is associated with diminished quality of life, cognitive impairment, cardiovascular morbidity, hospitalizations, and mortality. As the prevalence of end-stage renal disease continues to rise, the management of anemia represents a growing economic burden. Erythropoiesis-stimulating agents (ESA) are the mainstay of anemia management but their use is limited due to the associated cardiovascular adverse events. Prolyl hydroxylase domain enzyme (PHD) inhibitors are a new class of drugs that stabilize the hypoxia-inducible factors and are under clinical investigation for the treatment of renal anemia. The advantages of PHD inhibitors include the oral route of administration, improved iron profile, restoration of diurnal rhythm of erythropoietin secretion, and endogenous erythropoietin production near physiological range. Emerging but limited data indicates a small blood pressure lowering effect of PHD inhibitors. The effect of PHD inhibitors on cardiovascular endpoints and the potential risks of CKD progression and pulmonary hypertension remains to be addressed in the ongoing clinical trials. PMID- 26894600 TI - Valproic acid may exerts its cytotoxic effect through rassf1a expression induction in acute myeloid leukemia. AB - In acute myeloid leukemia (AML), despite the acceptance of standard intensive chemotherapy as an optimal induction regimen for all age groups, in the elderly patients, the best treatment should meet the challenge of multiple factors like age, comorbidities, and cytogenetics, making them ineligible for standard induction chemotherapy. Using the current low-intensity therapies like decitabine, azacitidine, and low-dose cytarabine as a single arm, outcomes for these patients remain poor. As a histone deacetylase inhibitor valproic acid (VPA) exhibit anticancer activity by triggering apoptosis, the mechanism of which is not yet completely clarified. To explore the possible connection between VPA treatment and the Hippo pathway as an apoptosis stimulating route, we also explore the expression of major components of this pathway and for the first time we postulate a relationship between VPA treatment and cell death induction through RASSF1A expression induction. Furthermore, we demonstrate that autophagy inhibition by chloroquine (CQ) significantly augmented the cytotoxic effect of VPA on AML cells, especially in those with unfavorable and normal karyotype. Regarding that VPA and CQ are well-tolerated drugs and our presumptive results of usefulness of VPA + CQ in three cytogenetic risk groups of AML, this combinatorial therapy could represent an attractive treatment option for older AML patients unfit for intensive therapy. PMID- 26894601 TI - Blockage of glutaminolysis enhances the sensitivity of ovarian cancer cells to PI3K/mTOR inhibition involvement of STAT3 signaling. AB - The PI3K/Akt/mTOR axis in ovarian cancer is frequently activated and implicated in tumorigenesis. Specific targeting of this pathway is therefore an attractive therapeutic approach for ovarian cancer. However, ovarian cancer cells are resistant to PP242, a dual inhibitor of mTORC1 and mTORC2. Interestingly, blockage of GLS1 with a selective inhibitor, CB839, or siRNA dramatically sensitized the PP242-induced cell death, as evident from increased PARP cleavage. The anti-cancer activity of CB-839 and PP242 was abrogated by the addition of the TCA cycle product alpha-ketoglutarate, indicating the critical function of GLS1 in ovarian cancer cell survival. Finally, glutaminolysis inhibition activated apoptosis and synergistically sensitized ovarian cancer cells to priming with the mTOR inhibitor PP242. GLS1 inhibition significantly reduced phosphorylated STAT3 expression in ovarian cancer cells. These findings show that targeting glutamine addiction via GLS1 inhibition offers a potential novel therapeutic strategy to overcome resistance to PI3K/Akt/mTOR inhibition. PMID- 26894602 TI - New insight on the biological role of p53 protein as a tumor suppressor: re evaluation of its clinical significance in triple-negative breast cancer. AB - While p53 mutation is found in the majority of triple-negative breast cancer (TNBC) and despite recent developments in p53-targeting agents, their therapeutic application is still limited by the absence of standard biomarkers and ambiguousness of its essential biological role in cancer. Whole sections from 305 TNBC cases were stained for p53 to determine the correlation with lymph node metastasis and clinical outcomes in the whole cohort as well as in stratified patient groups according to AJCC stage and the use of adjuvant chemotherapy. Reduced immunohistochemical expression of p53 was an independent risk factor for lymph node metastasis. p53 overexpression was predictive of better clinical outcome in all patients (P = 0.012, disease-free survival and P = 0.008, overall survival) and the stratified cohorts of those who had early breast cancer and received adjuvant chemotherapy. Suppression of endogenous mutant p53 by siRNA and induction of wild-type p53 repressed TNBC cell invasion in vitro. In TNBC, increased immunohistochemical expression of p53 may reflect the accumulation of wild-type p53 rather than the mutant form. Strong p53 protein expression may serve as a favorable prognostic indicator and provide evidence for the use of specific agents targeting p53. PMID- 26894603 TI - Crystal structure and chemotherapeutic efficacy of the novel compound, gallium tetrachloride betaine, against breast cancer using nanotechnology. AB - The objective of this study was to investigate the antitumor efficacy of a novel synthesized compound, betaine gallium-tetrachloride (BTG), alone or combined with ZnO-nanoparticles (BTG + ZnO-NPs) on the incidence of 7, 12-dimethylbenz anthrathene-induced mammary tumor in female rats. Crystal and molecular structure of the prepared BTG were identified using X-ray crystallography. In vitro study revealed BTG more cytotoxic than BTG + ZnO-NPs on human breast cancer (MCF-7) cell line. In vivo study demonstrated that the blood antioxidant status of tumor bearing rats (DMBA group) was significantly lower than normal noticeable by a significant decrease in GSH content, GPx, SOD, and CAT activities associated with a significantly high MDA content. Both treatments have significantly elevated SOD and CAT activities with a concomitant decrease of MDA level compared to DMBA group. However, BTG + ZnO-NPs accentuated the decrease of GSH regarding DMBA group. The results showed also that both treatments significantly activate caspase-3 enzyme and apoptosis in mammary glands. Their administration to tumor bearing rats was found to significantly reduce plasma iron and iron-binding capacity (TIBC) compared to DMBA group. Regarding liver function, both treatments significantly reduced the increase of ALT and AST activities compared to DMBA group. However, BTG + ZnO-NPs decreased albumin below normal level. Histopathological studies showed that normalization of tissue structures was higher in BTG than BTG + ZnO-NPs treatment. According to the results obtained, it is observed that the antitumor effect of BTG alone was as strong as BTG + ZnO-NPs and even more efficient in some aspects accordingly, a combination is not needed. Thus, the novel synthetic gallium derivatives may potentially present a new hope for the development of breast cancer therapeutics, which should attract further scientific and pharmaceutical interest. PMID- 26894604 TI - The role of Notch signaling in kidney podocytes. AB - The Notch signaling pathway is a basic cell-to-cell communication mechanism. This pathway is activated by the interaction between Notch receptors and the ligands of adjacent cells. Once activated, Notch receptors are cleaved and the intracellular domains translocate into the nucleus, where the transcription of target genes starts. In the mammalian kidney, Notch receptors are activated during nephrogenesis. Afterwards, in the mature glomeruli, the Notch pathway becomes silent. However, many researchers have reported the activation of Notch receptors in mature podocytes under pathological conditions. In this review, we discuss the role of Notch signaling in podocytes. PMID- 26894605 TI - Obstetric anal sphincter injuries after episiotomy: systematic review and meta analysis. AB - INTRODUCTION: There is conflicting evidence on whether mediolateral episiotomy (MLE) reduces the risk of obstetric anal sphincter injuries (OASI) in spontaneous vaginal deliveries (SVD). OBJECTIVES: A systematic review was undertaken to compare rates of OASI amongst women who had undergone mediolateral episiotomy versus those who did not. METHODS: ? SEARCH STRATEGY: Electronic searches were performed in literature databases: CINAHL, Cochrane, EMBASE, Medline and MIDIRS from database inception to July 2015. Studies were eligible if MLE was compared to spontaneous tears and if OASI was the outcome of interest. Two reviewers independently selected and extracted data on study characteristics, quality and results. We computed events of OASI in those who did and did not have an episiotomy from individual studies and pooled these results in a meta-analysis where possible. MAIN RESULTS: Of the 2090 citations, 16 were included in the review. All were non-randomised, population based or retrospective cohort studies. There was great variation in quality amongst these studies. Data from 7 studies was used for meta-analysis. On collating data from these studies where the majority of women (636755/651114) were nulliparous, MLE reduced the risk of OASI (RR 0.67 95 % CI 0.49-0.92) in vaginal delivery. CONCLUSION: The pooled analysis of a large number of women undergoing vaginal birth, most of who were nulliparous, indicates that MLE has a beneficial effect in prevention of OASI. An accurately given MLE might have a role in reducing OASI and should not be withheld, especially in nulliparous women. Caution is advised as the data is from non-randomised studies. PMID- 26894606 TI - Practices in pelvic organ prolapse operations among surgeons: an international survey identifying needs for further research. AB - OBJECTIVE AND HYPOTHESIS: Our aim was to identify variation in surgical technique for treating pelvic floor disorders looking specifically at differences in approach between subspeciality trained urogynaecologists and general gynaecologists. We hypothesised that speciality trained surgeons would have a more uniform operative technique. We did not make a hypothesis about which operative areas would have the most variation overall. METHODS: We performed a single-timepoint online survey of members of the International Urogynaecological Association (IUGA). Probability of difference from mean is presented as a raw value and significance of difference of means between surgical cohorts was calculated using the t test for independent variables. RESULTS: We received 205 responses from 118 general gynaecologists and 87 from subspecialty trained urogynaecologists (8 % response rate) to 27 questions concerning operative steps in four common urogynaecological operations. Surgeons had low levels of variation. The probability of any surgeon providing a different answer from the mode of their cohort was not significant within or between surgeons with and without subspeciality training (p = 0.47). Two areas with high levels of variation between surgeons were identified (probability of variation >0.5). These were: "In order to reduce cystocele, do you plicate the fascia covering the bladder or use vaginal tissue?" and "Would you usually plicate the rectovaginal facial septum to the vault?" CONCLUSIONS: Most urogynaecological surgeries were of similar technique; however there were two areas of significant variation between surgeons that may affect outcomes and warrant further study. PMID- 26894607 TI - Incidence of successful voiding and predictors of early voiding dysfunction after retropubic sling. AB - INTRODUCTION AND HYPOTHESIS: There is a paucity of literature on resumption of normal voiding predictors after synthetic retropubic sling insertion and lack of a standardized method of determination. Our goals were to determine the incidence of a successful voiding trial; whether clinical, operative, or urodynamic variables predict discharge with a catheter; and incidence of later retention in those who were initially successful. METHODS: We performed an internal-review board (IRB)-approved retrospective chart review of 229 consecutive patients who underwent retropubic sling (TVT, Boston Scientific, Natick, MA, USA)) from 2001 to 2010. Exclusions were concomitant surgery or cystotomy at the time of retropubic sling insertion. All participants underwent a voiding trial in recovery consisting of 300 cc sterile-water retrograde fill and were discharged home without a catheter after single void of at least 200 cc following catheter removal. RESULTS: Of 170 patients, 136 (80 %) passed the voiding trial the same day, with 165 (97 %) passing within 1 day. Factors associated with delayed voiding were age >=65 years (p < 0.05), presence of Valsalva voiding (p < 0.01), lower body mass index (BMI) (p < 0.05), and higher gravidity (p < 0.05) and parity (p < 0.01). Age >=65 years [adjusted odds ratio (aOR) 3.72, 95 % confidence interval (CI) 1.40-9.90, p < 0.01] and Valsalva voiding (aOR 3.89, 95 % CI 1.56-9.69, p < 0.01) remained significant independent predictors in multivariate analysis. CONCLUSIONS: The majority of patients with retropubic sling can be safely discharged home the same day without a catheter after retrograde fill. Women >65 years or Valsalva voiders had nearly four times the odds of being discharged with a catheter. Most patients resume normal voiding within 24 h after retropubic sling insertion, but >65 years and Valsalva voiding are risk factors for voiding inability at discharge. PMID- 26894608 TI - Acquired aplastic anemia in Korean children: treatment guidelines from the Bone Marrow Failure Committee of the Korean Society of Pediatric Hematology Oncology. AB - The treatment of choice for aplastic anemia (AA) in children has been HLA-matched family donor (MFD) hematopoietic stem cell transplantation (HSCT). For those lacking MFD, immunosuppressive therapy (IST) consisting of horse antithymocyte globulin (ATG) and cyclosporine has been successful. The choices of second and third line treatments are more complex and debatable, especially in the situation of unavailability of horse ATG. IST with rabbit ATG seems to be less effective. Recently, improved survival of non-MFD HSCTs has been documented. The outcome of matched or mismatched unrelated donor, umbilical cord blood, or haploidentical family donor transplantations will be discussed in AA children after IST failure. Experimental approaches of upfront HSCT using non-MFDs will be briefly touched. In this review, a treatment guideline for children with AA from the Korean Society of Pediatric Hematology Oncology will be presented along with a brief review of literature on current clinical practices in Korea. PMID- 26894609 TI - Approach to Rapid Synthesis and Functionalization of Iron Oxide Nanoparticles for High Gene Transfection. AB - Surface functionalization of theranostic nanoparticles (NPs) typically relies on lengthy, aqueous postsynthesis labeling chemistries that have limited ability to fine-tune surface properties and can lead to NP heterogeneity. The need for a rapid, simple synthesis approach that can provide great control over the display of functional moieties on NP surfaces has led to increased use of highly selective bioorthoganol chemistries including metal-affinity coordination. Here we report a simple approach for rapid production of a superparamagnetic iron oxide NPs (SPIONs) with tunable functionality and high reproducibility under aqueous conditions. We utilize the high affinity complex formed between catechol and Fe((III)) as a means to dock well-defined catechol modified polymer modules on the surface of SPIONs during sonochemical coprecipitation synthesis. Polymer modules consisted of chitosan and poly(ethylene glycol) (PEG) copolymer (CP) modified with catechol (CCP), and CCP functionalized with cationic polyethylenimine (CCP-PEI) to facilitate binding and delivery of DNA for gene therapy. This rapid synthesis/functionalization approach provided excellent control over the extent of PEI labeling, improved SPION magnetic resonance imaging (MRI) contrast enhancement and produced an efficient transfection agent. PMID- 26894610 TI - Effects of Aqueous Film-Forming Foams (AFFFs) on Trichloroethene (TCE) Dechlorination by a Dehalococcoides mccartyi-Containing Microbial Community. AB - The application of aqueous film-forming foams (AFFFs) to extinguish chlorinated solvent-fueled fires has led to the co-contamination of poly- and perfluoroalkyl substances (PFASs) and trichloroethene (TCE) in groundwater and soil. Although reductive dechlorination of TCE by Dehalococcoides mccartyi is a frequently used remediation strategy, the effects of AFFF and PFASs on TCE dechlorination are not well-understood. Various AFFF formulations, PFASs, and ethylene glycols were amended to the growth medium of a D. mccartyi-containing enrichment culture to determine the impact on dechlorination, fermentation, and methanogenesis. The community was capable of fermenting organics (e.g., diethylene glycol butyl ether) in all AFFF formulations to hydrogen and acetate, but the product concentrations varied significantly according to formulation. TCE was dechlorinated in the presence of an AFFF formulation manufactured by 3M but was not dechlorinated in the presence of formulations from two other manufacturers. Experiments amended with AFFF-derived PFASs and perfluoroalkyl acids (PFAAs) indicated that dechlorination could be inhibited by PFASs but that the inhibition depends on surfactant concentration and structure. This study revealed that the fermentable components of AFFF can stimulate TCE dechlorination, while some of the fluorinated compounds in certain AFFF formulations can inhibit dechlorination. PMID- 26894611 TI - Of dups and dinos: evolution at the K/Pg boundary. AB - Fifteen years into sequencing entire plant genomes, more than 30 paleopolyploidy events could be mapped on the tree of flowering plants (and many more when also transcriptome data sets are considered). While some genome duplications are very old and have occurred early in the evolution of dicots and monocots, or even before, others are more recent and seem to have occurred independently in many different plant lineages. Strikingly, a majority of these duplications date somewhere between 55 and 75 million years ago (mya), and thus likely correlate with the K/Pg boundary. If true, this would suggest that plants that had their genome duplicated at that time, had an increased chance to survive the most recent mass extinction event, at 66mya, which wiped out a majority of plant and animal life, including all non-avian dinosaurs. Here, we review several processes, both neutral and adaptive, that might explain the establishment of polyploid plants, following the K/Pg mass extinction. PMID- 26894612 TI - Photosynthetic sensitivity of phytoplankton to commonly used pharmaceuticals and its dependence on cellular phosphorus status. AB - Recently pharmaceuticals have become significant environmental pollutants in aquatic ecosystems, that could affect primary producers such as microalgae. Here we analyzed the effect of pharmaceuticals on the photosynthesis of microalgae commonly found in freshwater-two species of Chlorophyceae and a member of the Eustigmatophyceae, via PAM fluorometry. As pharmaceuticals, three medicines often consumed in households were chosen: (i) fluoxetine, an antidepressant, (ii) propranolol, a beta-blocker and (iii) ibuprofen, an anti-inflammatory and analgesic medicine. The EC50 for the quantum yield of photosystem II in phytoplankton acclimated to inorganic phosphorus (Pi)-replete and Pi-limited conditions was estimated. Acute toxicity experiments over a 5 h exposure revealed that Nannochloropsis limnetica was the least sensitive to pharmaceuticals in its photosynthetic yield out of all species tested. Although the estimation of sub lethal effects can be vital in contrast to that of LC50s, the EC50 values in all species and for all medicines were orders of magnitude higher than concentrations found in polluted surface water. Chlamydomonas reinhardtii was the most sensitive to fluoxetine (EC50 of 1.6 mg L(-1)), and propranolol (EC50 of 3 mg L(-1)). Acutodesmus obliquus was most sensitive to ibuprofen (EC50 of 288 mg L(-1)). Additionally, the sensitivity to the pharmaceuticals changed under a Pi limitation; the green algae became less sensitive to fluoxetine and propranolol. In contrast, Pi-limited algal species were more sensitive to ibuprofen. Our results suggest that the sensitivity of algae to pharmaceuticals is (i) highly compound- and species-specific and (ii) dependent on the cellular P status. PMID- 26894613 TI - Management of cancer-associated disseminated intravascular coagulation: guidance from the SSC of the ISTH: comment. PMID- 26894614 TI - Prevalence and nature of survivorship needs in patients with head and neck cancer. AB - BACKGROUND: The purpose of this study was to determine the number, type, and predictors of patients with head and neck cancer unmet survivorship needs. METHODS: This study accrued patients with head and neck cancer at any time point in their survivorship course, and they completed a survey, including demographic information and the Cancer Survivors' Unmet Needs Measure (CaSUN). RESULTS: The median age of the 158 participants was 64 years. Ninety-six patients (61%) reported at least one unmet need on the CaSUN and 6 patients had a very high number of needs between 31 and 35. The mean number of unmet needs was 5.8 +/- 8.9. Comprehensive Cancer Care was the most common domain of unmet need (n = 69; 45%). Younger age, earlier survivorship phase, and worse quality of life were associated with increased survivorship unmet needs on multivariable analysis. CONCLUSION: A high proportion of patients with head and neck cancer have unmet needs. These data can guide the development of head and neck survivorship programs. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: 1097-1103, 2016. PMID- 26894616 TI - Optical investigation of gold shell enhanced 25 nm diameter upconverted fluorescence emission. AB - We enhance the efficiency of upconverting nanoparticles by investigating the plasmonic coupling of 25 nm diameter NaYF4:Yb, Er nanoparticles with a gold-shell coating, and study the physical mechanism of enhancement by single-particle, time resolved spectroscopy. A three-fold overall increase in emission intensity, and five-fold increase of green emission for these plasmonically enhanced particles have been achieved. Using a combination of structural and fluorescent imaging, we demonstrate that fluorescence enhancement is based on the photonic properties of single, isolated particles. Time-resolved spectroscopy shows that the increase in fluorescence is coincident with decreased rise time, which we attribute to an enhanced absorption of infrared light and energy transfer from Yb(3+) to Er(3+) atoms. Time-resolved spectroscopy also shows that fluorescence life-times are decreased to different extents for red and green emission. This indicates that the rate of photon emission is not suppressed, as would be expected for a metallic cavity, but rather enhanced because the metal shell acts as an optical antenna, with differing efficiency at different wavelengths. PMID- 26894615 TI - Simultaneous oxidation of ammonium and cresol isomers in a sequencing batch reactor: physiological and kinetic study. AB - The aim of this study was to evaluate the physiological and kinetic capacities of a nitrifying consortium to simultaneously oxidize ammonium (138 mg N/L day), m cresol, o-cresol, and p-cresol (180 mg C/L day in mixture) in a sequencing batch reactor (SBR). A 1-L SBR was firstly operated without cresol addition (phase I) for stabilizing the nitrification respiratory process with ammonium consumption efficiencies close to 100 % and obtaining nitrate as the main end product. When cresols were added (phase II m-cresol (10, 20, and 30 mg C/L); phase III m-cresol (30 mg C/L) and o-cresol (10, 20, and 30 mg C/L); phase IV a mixture of three isomers (30 mg C/L each one)), inhibitory effects were evidenced by decreased values of the specific rates of nitrification compared with values from phase I. However, the inhibition diminished throughout the operation cycles, and the overall nitrifying physiological activity of the sludge was not altered in terms of efficiency and nitrate yield. The different cresols were totally consumed, being o-cresol the most recalcitrant. The use of SBR allowed a metabolic adaptation of the consortium to oxidize the cresols as the specific rates of consumption increased throughout the cycles, showing that this type of reactor can be a good alternative for treating industrial effluents in a unique reactor. PMID- 26894617 TI - Can Artificial Ecosystems Enhance Local Biodiversity? The Case of a Constructed Wetland in a Mediterranean Urban Context. AB - Constructed wetlands (CW) are considered a successful tool to treat wastewater in many countries: their success is mainly assessed observing the rate of pollution reduction, but CW can also contribute to the conservation of ecosystem services. Among the many ecosystem services provided, the biodiversity of CW has received less attention. The EcoSistema Filtro (ESF) of the Molentargius-Saline Regional Natural Park is a constructed wetland situated in Sardinia (Italy), built to filter treated wastewater, increase habitat diversity, and enhance local biodiversity. A floristic survey has been carried out yearly 1 year after the construction of the artificial ecosystem in 2004, observing the modification of the vascular flora composition in time. The flora of the ESF accounted for 54% of the whole Regional Park's flora; alien species amount to 12%; taxa of conservation concern are 6%. Comparing the data in the years, except for the biennium 2006/2007, we observed a continuous increase of species richness, together with an increase of endemics, species of conservation concern, and alien species too. Once the endemics appeared, they remained part of the flora, showing a good persistence in the artificial wetland. Included in a natural park, but trapped in a sprawling and fast growing urban context, this artificial ecosystem provides multiple uses, by preserving and enhancing biodiversity. This is particularly relevant considering that biodiversity can act as a driver of sustainable development in urban areas where most of the world's population lives and comes into direct contact with nature. PMID- 26894618 TI - Microbial Diversity of Chromium-Contaminated Soils and Characterization of Six Chromium-Removing Bacteria. AB - Three soil samples obtained from different sites adjacent to a chromium slag heap in a steel alloy factory were taken to examine the effect of chromium contamination on soil bacterial diversity as determined by construction of 16S rDNA clone libraries and sequencing of selected clones based on restriction fragment length polymorphism (RFLP) analysis. Results revealed that Betaproteobacteria, Gammaproteobacteria, Firmicutes, and Alphaproteobacteria occurred in all three soil samples, although the three samples differed in their total diversity. Sample 1 had the highest microbial diversity covering 12 different classes, while Sample 3 had the lowest microbial diversity. Strains of six different species were successfully isolated, one of which was identified as Zobellella denitrificans. To our knowledge, this is the first report of a strain belonging to the genus Zobellella able to resist and reduce chromium. Among all isolates studied, Bacillus odysseyi YH2 exhibited the highest Cr(VI)-reducing capability, with a total removal of 23.5 % of an initial Cr(VI) concentration of 350 mg L(-1). PMID- 26894619 TI - 754 exposures to reed diffusers reported to the United Kingdom National Poisons Information Service 2010-2014. AB - OBJECTIVE: The objective of this study is to review the reported toxicity of reed diffuser fragrance liquid which, in addition to essential oils, commonly contains glycol ethers but other ingredients and/or alternatives are 3-methoxy-3-methyl-1 butanol, petroleum distillates, ethanol and isopropanol. METHODS: We analysed retrospectively enquiries to the United Kingdom National Poisons Information Service between 1 January 2010 and 31 December 2014. RESULTS: 754 patients were exposed to reed diffusers; the majority (n = 712) were children < 5 years. Ingestion was the most common route of exposure (706 of 754 patients) and involved the liquid alone (n = 570), water beads alone (n = 84), sucking on the reeds (n = 31) or ingesting the liquid and water beads (n = 21). The reported amount of fragrance liquid ingested was known in only 76 of 591 cases (12.9%), with a median (IQR) volume of 20.0 (IQR = 10-40) mL. The WHO/IPCS/EC/EAPCCT Poisoning Severity Score (PSS) was known in 702 of 706 sole ingestions: in 574 (81.3%), the PSS was 0 (asymptomatic); in 117 (16.6%) patients, the PSS was 1 (minor toxicity); in 11 (1.6%), the PSS was 2 (moderate toxicity); there were no patients with features graded PSS 3 (severe toxicity). Significantly (p = 0.008) more patients became symptomatic (PSS 1 and PSS 2) following the ingestion of a reed diffuser containing 3-methoxy-3-methyl-1-butanol than propylene glycol monobutyl ether, though there was no significant difference when compared with those containing dipropylene glycol monomethyl ether (p = 0.181). The most common features following ingestion of fragrance liquid were nausea and vomiting (n = 53), coughing (n = 17) and CNS depression (n = 9). Seven patients suffered eye exposure alone: two developed eye pain and four conjunctivitis. Dermal exposure alone was reported in six patients, two of whom developed skin irritation. CONCLUSIONS: The majority of patients in our study developed no features or only minor symptoms following ingestion of reed diffuser fragrance liquid. PMID- 26894621 TI - Effectiveness of Chlorhexidine Wipes for the Prevention of Multidrug-Resistant Bacterial Colonization and Hospital-Acquired Infections in Intensive Care Unit Patients: A Randomized Trial in Thailand. AB - OBJECTIVE: To determine the effectiveness of daily bathing with 2% chlorhexidine impregnated washcloths in preventing multidrug-resistant (MDR) gram-positive bacterial colonization and bloodstream infection. METHODS: A randomized, open label controlled trial was conducted in 4 medical intensive care units (ICUs) in Thailand from December 2013 to January 2015. Patients were randomized to receive cleansing with non-antimicrobial soap (control group) or 2% chlorhexidine impregnated washcloths used to wipe the patient's body once daily (chlorhexidine group). Swabs were taken from nares, axilla, antecubital, groin, and perianal areas on admission and on day 3, 5, 7, and 14. The 5 outcomes were (1) favorable events ( all samples negative throughout ICU admission, or initially positive samples with subsequent negative samples); (2) MDR bacteria colonization-free time; (3) hospital-acquired infection; (4) length of ICU and hospital stay; (5) adverse skin reactions. RESULTS: A total of 481 patients were randomly assigned to the control group (241) or the chlorhexidine group (240). Favorable events at day 14 were observed in 34.8% of patients in the control group and 28.6% in the chlorhexidine group (P=.79). Median MDR bacteria colonization-free times were 5 days in both groups. The incidence rate of hospital-acquired infection and the length of the ICU and hospital stay did not differ significantly between groups. The incidence of adverse skin reactions in the chlorhexidine group was 2.5%. CONCLUSION: The effectiveness of 2% chlorhexidine-impregnated washcloths for the prevention of MDR gram-negative bacteria colonization and hospital-acquired infection in adult patients in ICU was not proven. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT01989416. PMID- 26894620 TI - Epiregulin is required for lung tumor promotion in a murine two-stage carcinogenesis model. AB - Adenocarcinoma accounts for ~40% of lung cancer, equating to ~88 500 new patients in 2015, most of who will succumb to this disease, thus, the public health burden is evident. Unfortunately, few early biomarkers as well as effective therapies exist, hence the need for novel targets in lung cancer treatment. We previously identified epiregulin (Ereg), an EGF-like ligand, as a biomarker in several mouse lung cancer models. In the present investigation we used a primary two-stage initiation/promotion model to test our hypothesis that Ereg deficiency would reduce lung tumor promotion in mice. We used 3-methylcholanthrene (initiator) or oil vehicle followed by multiple weekly exposures to butylated hydroxytoluene (BHT; promoter) in mice lacking Ereg (Ereg-/- ) and wildtype controls (BALB/ByJ; Ereg+/+ ) and examined multiple time points and endpoints (bronchoalveolar lavage analysis, tumor analysis, mRNA expression, ELISA, wound assay) during tumor promotion. At the early time points (4 and 12 wk), we observed significantly reduced amounts of inflammation (macrophages, PMNs) in the Ereg-/- mice compared to controls (Ereg+/+ ). At 20 wk, tumor multiplicity was also significantly decreased in the Ereg-/- mice versus controls (Ereg+/+ ). IL10 expression, an anti-inflammatory mediator, and downstream signaling events (Stat3) were significantly increased in the Ereg-/- mice in response to BHT, supporting both reduced inflammation and tumorigenesis. Lastly, wound healing was significantly increased with recombinant Ereg in both human and mouse lung epithelial cell lines. These results indicate that Ereg has proliferative potential and may be utilized as an early cancer biomarker as well as a novel potential therapeutic target. (c) 2016 Wiley Periodicals, Inc. PMID- 26894622 TI - Beyond Infection: Device Utilization Ratio as a Performance Measure for Urinary Catheter Harm. AB - Catheter-associated urinary tract infection (CAUTI) is considered a reasonably preventable event in the hospital setting, and it has been included in the US Department of Health and Human Services National Action Plan to Prevent Healthcare-Associated Infections. While multiple definitions for measuring CAUTI exist, each has important limitations, and understanding these limitations is important to both clinical practice and policy decisions. The National Healthcare Safety Network (NHSN) surveillance definition, the most frequently used outcome measure for CAUTI prevention efforts, has limited clinical correlation and does not necessarily reflect noninfectious harms related to the catheter. We advocate use of the device utilization ratio (DUR) as an additional performance measure for potential urinary catheter harm. The DUR is patient-centered and objective and is currently captured as part of NHSN reporting. Furthermore, these data are readily obtainable from electronic medical records. The DUR also provides a more direct reflection of improvement efforts focused on reducing inappropriate urinary catheter use. PMID- 26894623 TI - Catheter Matters. PMID- 26894624 TI - Clostridium difficile--To Test or Not to Test? Response to Kundrapu et al. PMID- 26894625 TI - Response to Prior and Fitzpatrick. PMID- 26894627 TI - Greetings to ISRHML Attendees and Researchers. PMID- 26894626 TI - Using Gelatin Nanoparticle Mediated Intranasal Delivery of Neuropeptide Substance P to Enhance Neuro-Recovery in Hemiparkinsonian Rats. AB - PURPOSE: Intranasal administration of phospholipid-based gelatin nanoparticles (GNP) was prepared to investigate the neuro-recovery effects of neuropeptide Substance P (SP) on hemiparkinsonian rats. METHODS: The SP-loaded gelatin nanoparticles (SP-GNP) were prepared by a water-in-water emulsion method and possessed high stability, encapsulating efficiency and loading capacity. PC-12 cells were used to examine the growth enhancement of SP-GNP in vitro by MTT assays and flow cytometry (FCM). The therapeutic effects of SP-GNP on 6 hydroxydopamine (6-OHDA) induced hemiparkinsonian rats were assessed by quantifying rotational behavior and the levels of tyrosine hydroxylase (TH), phosphorylated c-Jun protein (p-c-Jun) and Caspase-3 (Cas-3) expressed in substantia nigra (SN) region of hemiparkinsonian rats. RESULTS: PC-12 cells under SP-GNP treatment showed better cell viability and lower degree of apoptosis than those under SP solution treatment. Hemiparkinsonian rats under intranasal SP-GNP administration demonstrated better behavioral improvement, higher level of TH in SN along with much lower extent of p-c-Jun and Cas-3 than those under intranasal SP solution administration and intravenous SP-GNP administration. CONCLUSIONS: With the advantages of GNP and nose-to-brain pathway, SP can be effectively delivered into the damaged SN region and exhibit its neuro-recovery function through the inhibition on JNK pathway and dopaminergic neuron apoptosis. PMID- 26894628 TI - A Randomized Comparison Between Conventional and Waveform-Confirmed Loss of Resistance for Thoracic Epidural Blocks. AB - BACKGROUND AND OBJECTIVES: Epidural waveform analysis (EWA) provides a simple confirmatory adjunct for loss of resistance (LOR): when the needle tip is correctly positioned inside the epidural space, pressure measurement results in a pulsatile waveform. In this randomized trial, we compared conventional and EWA confirmed LOR in 2 teaching centers. Our research hypothesis was that EWA confirmed LOR would decrease the failure rate of thoracic epidural blocks. METHODS: One hundred patients undergoing thoracic epidural blocks for thoracic surgery, abdominal surgery, or rib fractures were randomized to conventional LOR or EWA-LOR. The operator was allowed as many attempts as necessary to achieve a satisfactory LOR (by feel) in the conventional group. In the EWA-LOR group, LOR was confirmed by connecting the epidural needle to a pressure transducer using a rigid extension tubing. Positive waveforms indicated that the needle tip was positioned inside the epidural space. The operator was allowed a maximum of 3 different intervertebral levels to obtain a positive waveform. If waveforms were still absent at the third level, the operator simply accepted LOR as the technical end point. However, the patient was retained in the EWA-LOR group (intent-to-treat analysis).After achieving a satisfactory tactile LOR (conventional group), positive waveforms (EWA-LOR group), or a third intervertebral level with LOR but no waveform (EWA-LOR group), the operator administered a 4-mL test dose of lidocaine 2% with epinephrine 5 MUg/mL. Fifteen minutes after the test dose, a blinded investigator assessed the patient for sensory block to ice. RESULTS: Compared with LOR, EWA-LOR resulted in a lower rate of primary failure (2% vs 24%; P = 0.002). Subgroup analysis based on experience level reveals that EWA-LOR outperformed conventional LOR for novice (P = 0.001) but not expert operators. The performance time was longer in the EWA-LOR group (11.2 +/- 6.2 vs 8.0 +/- 4.6 minutes; P = 0.006). Both groups were comparable in terms of operator's level of expertise, depth of the epidural space, approach, and LOR medium. In the EWA-LOR group, operators obtained a pulsatile waveform with the first level attempted in 60% of patients. However, 40% of subjects required performance at a second or third level. CONCLUSIONS: Compared with its conventional counterpart, EWA-confirmed LOR results in a lower failure rate for thoracic epidural blocks (2% vs 24%) in our teaching centers. Confirmatory EWA provides significant benefits for inexperienced operators. PMID- 26894630 TI - Developing a vaccine to prevent otitis media caused by nontypeable Haemophilus influenzae. AB - Nontypeable Haemophilus influenzae (NTHi) is a predominant organism of the upper respiratory nasopharyngeal microbiota. Its disease spectrum includes otitis media, sinusitis, non-bacteremic pneumonia and invasive infections. Protein-based vaccines to prevent NTHi infections are needed to alleviate these infections in children and vulnerable populations such as the elderly and those with chronic obstructive pulmonary disease (COPD). One NTHi protein is included in a pneumococcal conjugate vaccine and has been shown to provide efficacy. Our lab has been interested in understanding the immunogenicity of NTHi vaccine candidates P6, protein D and OMP26 for preventing acute otitis media in young children. We expect that continued investigation and progress in the development of an efficacious protein based vaccine against NTHi infections is achievable in the near future. PMID- 26894629 TI - Parasitic diseases of the central nervous system: lessons for clinicians and policy makers. AB - Parasitic diseases of the central nervous system are associated with high mortality and morbidity, especially in resource-limited settings. The burden of these diseases is amplified as survivors are often left with neurologic sequelae affecting mobility, sensory organs, and cognitive functions, as well as seizures/epilepsy. These diseases inflict suffering by causing lifelong disabilities, reducing economic productivity, and causing social stigma. The complexity of parasitic life cycles and geographic specificities, as well as overlapping clinical manifestations in the host reflecting the diverse pathogenesis of parasites, can present diagnostic challenges. We herein provide an overview of these parasitic diseases and summarize clinical aspects, diagnosis, therapeutic strategies and recent milestones, and aspects related to prevention and control. PMID- 26894632 TI - Applicability of endoscopic indices in the determination of disease activity in patients with ulcerative colitis. AB - OBJECTIVE: The combination of clinical remission and mucosal healing represents a major goal of different treatment strategies for ulcerative colitis (UC). This study aimed to assess which of the endoscopic indices used to evaluate mucosal changes in UC are correlated with clinical indices currently used to determine disease activity, as well as which of the endoscopic indices are correlated with the Geboes Index used for histological evaluation. It also aimed to find correlations between the currently used clinical activity indices and the histological Geboes Index. METHODS: A group of 49 patients with a confirmed diagnosis of UC and a group of 52 individuals without a diagnosis of gastrointestinal disease, who constituted the control group, were investigated. All patients were evaluated by colonoscopy, and the severity of mucosal changes was scored in terms of nine different endoscopic indices commonly used in both pharmacological trials and clinical practice. Evaluation was also carried out using clinical and histological indices. Endoscopic indices used for UC were then correlated with different clinical and histological indices to find the strongest correlations. RESULTS AND CONCLUSION: A high correlation was demonstrated between three of the 11 evaluated clinical indices - Improvement Based on Individual Symptom Scores, Ulcerative Colitis Disease Activity Index, and Schroeder Index - and all nine endoscopic indices - Ulcerative Colitis Endoscopic Index of Severity, Baron Score, Schroeder Index, Feagan Index, Powell-Tuck Index, Rachmilewitz Index, Sutherland Index, Lofberg Index, and Lemman Index. Improvement Based on Individual Symptom Scores was the index with the highest correlation with all the endoscopic indices used for UC. The above indices are recommended for clinical evaluation of UC activity. The Ulcerative Colitis Endoscopic Index of Severity was moderately correlated with a histological index, and it is therefore recommended for routine endoscopic mucosal evaluation in patients with UC. PMID- 26894631 TI - A Stable Thoracic Hox Code and Epimorphosis Characterize Posterior Regeneration in Capitella teleta. AB - Regeneration, the ability to replace lost tissues and body parts following traumatic injury, occurs widely throughout the animal tree of life. Regeneration occurs either by remodeling of pre-existing tissues, through addition of new cells by cell division, or a combination of both. We describe a staging system for posterior regeneration in the annelid, Capitella teleta, and use the C. teleta Hox gene code as markers of regional identity for regenerating tissue along the anterior-posterior axis. Following amputation of different posterior regions of the animal, a blastema forms and by two days, proliferating cells are detected by EdU incorporation, demonstrating that epimorphosis occurs during posterior regeneration of C. teleta. Neurites rapidly extend into the blastema, and gradually become organized into discrete nerves before new ganglia appear approximately seven days after amputation. In situ hybridization shows that seven of the ten Hox genes examined are expressed in the blastema, suggesting roles in patterning the newly forming tissue, although neither spatial nor temporal co linearity was detected. We hypothesized that following amputation, Hox gene expression in pre-existing segments would be re-organized to scale, and the remaining fragment would express the complete suite of Hox genes. Surprisingly, most Hox genes display stable expression patterns in the ganglia of pre-existing tissue following amputation at multiple axial positions, indicating general stability of segmental identity. However, the three Hox genes, CapI-lox4, CapI lox2 and CapI-Post2, each shift its anterior expression boundary by one segment, and each shift includes a subset of cells in the ganglia. This expression shift depends upon the axial position of the amputation. In C. teleta, thoracic segments exhibit stable positional identity with limited morphallaxis, in contrast with the extensive body remodeling that occurs during regeneration of some other annelids, planarians and acoel flatworms. PMID- 26894633 TI - Obstructive sleep apnea is associated with fatty liver index, the index of nonalcoholic fatty liver disease. AB - BACKGROUND AND OBJECTIVES: The relationship between obstructive sleep apnea (OSA) and nonalcoholic fatty liver disease (NAFLD) is gaining increased attention. The aim of the present study was to examine the relationship of OSA with NAFLD defined by an elevated fatty liver index (FLI). MATERIALS AND METHODS: A total of 319 consecutive patients who underwent standard polysomnography were enrolled. Fasting blood samples were obtained from all patients for biological profile measurements, and demographic data were collected. Values of FLI were determined and assessed as predictors of the presence of NAFLD, as measured by ultrasound. The discriminative ability of FLI was estimated on the basis of the area under the receiver operator characteristic curve. RESULTS: An FLI of 60 achieved the highest diagnostic accuracy and yielded an area under the receiver operator characteristic curve of 0.822 (95% confidence interval: 0.729-0.916) in the detection of NAFLD. Patients with an FLI of 60 or higher had a significantly lower lowest O2 saturation (73 vs. 83%, P<0.001), a lower mean nocturnal oxygen saturation (93 vs. 95%, P<0.001), a higher apnea-hypopnea index (39.7 vs. 18.4, P<0.001), a higher oxygen desaturation index (39 vs. 10.6, P<0.001), and a higher percentage of sleep time spent with SpO2 less than 90% (4.63 vs. 0.92%, P<0.001) compared with those with FLI less than 60. In multivariate analysis, the presence of OSA was independently associated with elevated FLI after adjusting for confounding factors (odds ratio: 5.141, 95% confidence interval: 1.414-18.696, P=0.013). CONCLUSION: Our results suggest a positive association between the severity of OSA and NAFLD defined by an elevated FLI, which may serve as a good biomarker for detecting NAFLD in OSA patients. PMID- 26894634 TI - European experience with methotrexate treatment in Crohn's disease: a multicenter retrospective analysis. AB - INTRODUCTION: Methotrexate (MTX) has been utilized for the treatment of Crohn's disease (CD) for decades. Nevertheless, current data provide equivocal evidence on the efficacy of MTX in CD.The aims of this study were to describe the efficacy of MTX for maintenance of remission in CD and to identify the factors associated with the probability of steroid-free clinical remission in a multicenter European referral center cohort. PATIENTS AND METHODS: This was a retrospective cohort analysis. Consecutive patients treated with MTX for CD were included from 11 referral centers. Patients receiving concomitant treatment with tumor necrosis factor inhibitors or thiopurines were excluded. The main outcome was steroid-free clinical remission; the secondary outcomes included the rate of complications leading to MTX discontinuation and duration of relapse-free survival in patients achieving the main outcome. RESULTS: Between July 1992 and January 2012, 118 patients were identified for inclusion. MTX administration route was oral for induction in 31.4% and for maintenance in 49.1% of the patients. Steroid-free remission was achieved in 44/118 (37.2%) patients and was maintained relapse free by 28/44 (63.6%) for a median of 12 (3.5-18.5) months. At least one adverse effect was reported by 28.9% of the patients. No clinical or demographic factors were associated with either likelihood of achieving a clinical response or duration of relapse-free survival. CONCLUSION: MTX treatment induced steroid-free clinical remission in over a third of CD patients and maintained it for a year in almost two-thirds of the responders. MTX should be considered a viable therapeutic option in CD patients refractory to other therapies. PMID- 26894635 TI - Configuration Control in the Synthesis of Homo- and Heteroleptic Bis(oxazolinylphenolato/thiazolinylphenolato) Chelate Ligand Complexes of Oxorhenium(V): Isomer Effect on Ancillary Ligand Exchange Dynamics and Implications for Perchlorate Reduction Catalysis. AB - This study develops synthetic strategies for N,N-trans and N,N-cis Re(O)(LO-N)2Cl complexes and investigates the effects of the coordination spheres and ligand structures on ancillary ligand exchange dynamics and catalytic perchlorate reduction activities of the corresponding [Re(O)(LO-N)2](+) cations. The 2-(2' hydroxyphenyl)-2-oxazoline (Hhoz) and 2-(2'-hydroxyphenyl)-2-thiazoline (Hhtz) ligands are used to prepare homoleptic N,N-trans and N,N-cis isomers of both Re(O)(hoz)2Cl and Re(O)(htz)2Cl and one heteroleptic N,N-trans Re(O)(hoz)(htz)Cl. Selection of hoz/htz ligands determines the preferred isomeric coordination sphere, and the use of substituted pyridine bases with varying degrees of steric hindrance during complex synthesis controls the rate of isomer interconversion. The five corresponding [Re(O)(LO-N)2](+) cations exhibit a wide range of solvent exchange rates (1.4 to 24,000 s(-1) at 25 degrees C) and different LO-N movement patterns, as influenced by the coordination sphere of Re (trans/cis), the noncoordinating heteroatom on LO-N ligands (O/S), and the combination of the two LO-N ligands (homoleptic/heteroleptic). Ligand exchange dynamics also correlate with the activity of catalytic reduction of aqueous ClO4(-) by H2 when the Re(O)(LO-N)2Cl complexes are immobilized onto Pd/C. Findings from this study provide novel synthetic strategies and mechanistic insights for innovations in catalytic, environmental, and biomedical research. PMID- 26894636 TI - Considering the influence of stimulation parameters on the effect of conventional and high-definition transcranial direct current stimulation. AB - Recently, techniques to non-invasively modulate specific brain areas gained popularity in the form of transcranial direct current stimulation (tDCS) and high definition transcranial direct current stimulation. These non-invasive techniques have already shown promising outcomes in various studies with healthy subjects as well as patient populations. Despite widespread dissemination of tDCS, there remain significant unknowns about the influence of a diverse number of tDCS parameters (e.g. polarity, size, position of electrodes & duration of stimulation) in inducing neurophysiological and behavioral effects. This article explores both techniques starting with the history of tDCS, to the differences between conventional tDCS and high-definition transcranial direct current stimulation, the underlying physiological mechanism, the (in)direct effects, the applications of tDCS with varying parameters, the efficacy, the safety issues and the opportunities for future research. PMID- 26894637 TI - Photoluminescence properties of Yb(2+) ions doped in the perovskites CsCaX3 and CsSrX3 (X = Cl, Br, and I) - a comparative study. AB - The Yb(2+)-doped perovskite derivatives CsMX3 (M = Ca and Sr; X = Cl, Br, and I) are ideal systems for obtaining a detailed insight into the structure luminescence relationship of divalent lanthanides. The investigation of the respective photoluminescence properties yielded two emission bands in the violet and blue spectral range for all compounds, which are assigned to the spin-allowed and spin-forbidden 5d-4f transitions, respectively. The impact on their energetic positions is dependent on both the covalency of the Yb(2+)-halide bond and the corresponding bond length in agreement with expectations. The excitation spectra provide a detailed fine structure at low temperatures and can be partly interpreted separating the 4f(13) core from the 5d electron in the excited state. The local crystal field in CsSrI3:Yb(2+) provides a special case due to the trigonal distortion induced by the crystal structure that is clearly evident in the luminescence features of Yb(2+). The structure-property relationship of several spectroscopic key quantities of Yb(2+) in this series of halides is analyzed in detail and parallels the properties of Eu(2+) ions doped in the given perovskites. PMID- 26894638 TI - Research progress on polyoxometalate-based transition-metal-rare-earth heterometallic derived materials: synthetic strategies, structural overview and functional applications. AB - With the rapid development of science and technology and the trend of multidisciplinary pervasion, POM-based TM-RE heterometallic chemistry (POM = polyoxometalate, TM = transition-metal, RE = rare-earth) has become one of the most rapidly growing and challengeable areas of inorganic chemistry due to the impressive structural diversities, various chemical compositions and potential applications of these materials in magnetism, optics, electrochemistry, electrocatalysis and materials science. Over the past several years, continuous interest and persisting efforts have been dedicated to the preparation and exploration of POM-based TM-RE heterometallic derived materials (PTRHDMs), which have led to more than two hundred PTRHDMs. In this review, we summarize the structural types of reported PTRHDMs together with synthetic strategies, structural motifs and relevant functional applications. The exciting array of this emerging research theme presages continuous growth and great vitality. In the last section, some prospects of this branch are also presented and possible guidance for future work is outlined. PMID- 26894639 TI - Costs and Complications of Short Versus Long Cephalomedullary Nailing of OTA 31 A2 Proximal Femur Fractures in U.S. Veterans. AB - OBJECTIVES: In fractures without subtrochanteric extension, the indications for the use of short versus long cephalomedullary nails (CMNs) for intertrochanteric femur fractures are unclear. We hypothesized that long nails would be associated with higher costs and similar complication rates. DESIGN: Retrospective comparative study. SETTING: United States Department of Veterans Affairs Medical Centers. PARTICIPANTS: Patients receiving CMNs for OTA 31-A2 pertrochanteric fractures from 2001 to 2010. INTERVENTIONS: Short versus long cephalomedullary nailing. MAIN OUTCOME MEASUREMENTS: Costs, perioperative complications, readmissions, surgical failures, and mortality. RESULTS: We identified 262 patients with OTA 31-A2 pertrochanteric fractures (125 treated with short CMNs and 137 treated with long CMNs). The 2 cohorts had similar demographic and medical characteristics. There were no significant differences in perioperative complications, readmissions within 30 days, surgical failures within one year, or death within 30 days or one year. The average cost of hospitalization was significantly higher for the cohort treated with long nails (greater than $7000 in actual costs, and greater than $3000 when statistically adjusted for differences in postoperative lengths of stay). Multivariable analyses showed no significant differences in the rates of development of at least one complication, readmission, or death. CONCLUSIONS: In a cohort of patients with similar characteristics and fracture patterns, the use of long CMNs was associated with similar rates of complications, readmission, and reoperations, but significantly higher costs than with the use of short nails. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence. PMID- 26894640 TI - Suprapatellar Versus Infrapatellar Tibial Nail Insertion: A Prospective Randomized Control Pilot Study. AB - PURPOSE: The purpose of this OTA-approved pilot study was to compare the clinical and functional outcomes of the knee joint after infrapatellar (IP) versus suprapatellar (SP) tibial nail insertion. DESIGN: Prospective, randomized. SETTING: Level I trauma center. METHODS: After institutional review board approval, skeletally mature patients with OTA 42 tibial shaft fractures were randomized into either an IP or SP nail insertion group after informed consent was obtained. The SP also underwent prenail and postnail insertion patella femoral (PF) joint arthroscopy. Patients underwent follow-up (6 weeks, 3, 6, and 12 months) with standard radiographs, as well as visual analog score and pain diagram documentation. At the 6-month and 12-month visits, knee function questionnaires (Lysholm knee scale and SF-36) were completed. Magnetic resonance imaging/image (MRI) of the affected knee was obtained at 12 months. Ten patients in each group were required for a power analysis for the anticipated larger randomized control trial, but enrollment in each arm was not limited because of known problems with patient follow-up over a 12-month period. RESULTS: A total of 41 patients/fractures were enrolled in this study. Of those, only 25 patients/fractures (14 IP, 11 SP) fully complied with and completed 12 months of follow-up. Six of 11 SP presented with articular changes (chondromalacia) in the PF joint during the preinsertion arthroscopy. Three patients displayed a change in the articular cartilage based on postnail insertion arthroscopy. At 12 months, all fractures in both groups had proceeded to union. There were no differences between the affected and unaffected knee with respect to range of motion. Functional visual analog score and Lysholm knee scores showed no significant differences between groups (P > 0.05). The SF-36v2 comparison also revealed no significant differences in the overall score, all 4 mental components, and 3/4 physical components (P > 0.05). The bodily pain component score was superior in the SP group (45 vs. 36, P = 0.035). All 11 SP patients obtained MRIs at 1 year. Five of these patients had evidence of chondromalacia on MRI. These findings did not correlate with either the prenail or postnail insertion arthroscopy. Importantly, no patient in the SP group with postnail insertion arthroscopic changes had PF joint pain at 1 year. CONCLUSIONS: Overall, there seemed to be no significant differences in pain, disability, or knee range of motion between these 2 tibial intramedullary nail insertion techniques after 12 months of follow up. Based on this pilot study data, larger prospective trial with long-term follow-up is warranted. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence. PMID- 26894641 TI - To the Editor. PMID- 26894642 TI - In response. PMID- 26894643 TI - Remote Stereoinductive Intramolecular Nitrile Oxide Cycloaddition: Asymmetric Total Synthesis and Structure Revision of (-)-11beta-Hydroxycurvularin. AB - The first total synthesis and structure revision of (-)-11beta-hydroxycurvularin (1b), a macrolide possessing a beta-hydroxyketone moiety, were accomplished. The beta-hydroxyketone moiety in this natural product was introduced by cleavage of the N-O bond in an isoxazoline ring that was formed diastereoselectively in a 1,5 remote stereocontrolled fashion by employing intramolecular nitrile oxide cycloaddition. PMID- 26894644 TI - Reduced RKIP Expression is Associated With Breast Neoplastic Progression and is Correlated With Poor Outcomes and Aberrant Methylation in Breast Carcinoma. AB - Raf kinase inhibitor protein's (RKIP) downregulation can predict poor outcome in patients with various types of malignancy. In this study, we aimed to assess the potential involvement of RKIP in breast carcinogenesis and to evaluate its association with outcome variables and aberrant promoter methylation in breast carcinoma (BC). Tissue microarray sections were immunostained for RKIP in 26 normal breasts, 25 usual ductal hyperplasia, 76 ductal carcinoma in situ, and 198 BC specimens. The methylation status of RKIP was also determined in BC. In addition, the mRNA and protein level of RKIP was analyzed in 8 pairs of BC tissues and surrounding normal tissues by quantitative real-time polymerase chain reaction and Western blot analysis, respectively. RKIP mRNA and protein expression was significantly downregulated in BC tissues compared with the surrounding normal tissues (P<0.05 and P<0.01, respectively). Reduced RKIP expression seemed to increase progressively from normal breast to BC (P<0.001). Reduced RKIP expression was significantly associated with metastatic relapse (P<0.001) and was identified as an independent adverse prognostic indicator for disease-free survival (P=0.003). Reduced RKIP expression in BC was significantly correlated with its aberrant promoter methylation (P<0.05). In conclusion, downregulation of RKIP plays an important role in the breast neoplastic progression and correlates with poor prognosis in patients with BC. Aberrant RKIP methylation is one of the mechanisms that lead to downregulation of RKIP in BC. PMID- 26894645 TI - Mismatch Repair Protein Expression in Fordyce Granules. AB - Fordyce spots are a frequent condition under which sebaceous glands are found in the oral mucosa. There are 2 studies in the literature that have found an association between Fordyce spots and either Muir-Torre syndrome or Lynch syndrome. Despite this, no study on the expression of mismatch repair (MMR) proteins has been performed on biopsies of Fordyce granules. In this study, we intend to study the expression of MMR proteins under Fordyce condition. We investigated 9 cases of Fordyce spots of the oral mucosa from 6 men and 3 women, using immunohistochemistry with antibodies for the MutS protein homolog 6 (MSH6), MutS protein homolog 2 (MSH2), MutL protein homolog 1 (MLH1), and postmeiotic segregation increased 2 (PMS2). All cases showed the preservation of the expression of all markers. Even though a strong association has been demonstrated between Lynch syndrome and Fordyce spots, our study suggests that studying the biopsies of Fordyce condition by immunohistochemistry for MMR proteins might not be necessary. PMID- 26894646 TI - VE1 Immunohistochemistry Fails to Detect Most of the Non-BRAFV600E Mutations in Melanoma. PMID- 26894647 TI - Increased Expression of ALDH1A1 in Prostate Cancer is Correlated With Tumor Aggressiveness: A Tissue Microarray Study of Iranian Patients. AB - INTRODUCTION: Subpopulations of prostate cancer (PCa) cells expressing putative stem cell markers possess the ability to promote tumor growth, maintenance, and progression. This study aimed to evaluate the expression patterns and clinical significance of putative stem cell marker aldehyde dehydrogenase 1 A1 (ALDH1A1) in prostate tumor tissues. MATERIALS AND METHODS: ALDH1A1 expression was examined in a well-defined series of prostate tissues, including 105 (68%) samples of PCa, 21 (13%) samples of high-grade prostatic intraepithelial neoplasia, and 31 (19%) samples of benign prostate hyperplasia, which were embedded in tissue microarray blocks. The correlation of ALDH1A1 expression with clinicopathologic parameters was also assessed. RESULTS: There was a significant difference between the expression level of ALDH1A1 in PCa compared with the high-grade prostatic intraepithelial neoplasia and benign prostate hyperplasia samples (P<0.001). PCa cells expressing ALDH1A1 were more often seen in samples with advanced Gleason score (P=0.05) and high serum prostate specific antigen level (P=0.02). In addition, a positive correlation was found between ALDH1A1 expression and primary tumor stage and regional lymph node involvement (P=0.04 and 0.03, respectively). CONCLUSIONS: The significant association between ALDH1A1 expressions with Gleason score indicates the potential role of this protein in PCa tumorigenesis and aggressive behavior; therefore, this cancer stem cell marker can be used as a promising candidate for targeted therapy of PCa, especially those with high Gleason score. PMID- 26894648 TI - Chronic Lymphocytic Leukemia With Hodgkin and Reed-Sternberg (HRS) Cells: A Potential Diagnostic Pitfall in Lymph Node Biopsies. AB - Chronic lymphocytic leukemia (CLL) is known to undergo Richter transformation in a proportion of cases. Transformation into Hodgkin lymphoma has been described in a minority of the cases. However, CLL rarely also shows Hodgkin and Reed Sternberg cells with a classic morphology and the immunophenotype of Hodgkin lymphoma, even when not in transformation. The presence of these Hodgkin and Reed Sternberg cells in CLL can cause a diagnostic dilemma. PMID- 26894649 TI - TGF-beta and CTGF are Mitogenic Output Mediators of Wnt/beta-Catenin Signaling in Desmoid Fibromatosis. AB - Desmoid fibromatosis is a locally aggressive clonal fibroblastic proliferation with high recurrence rates and no metastatic potential. Implicated molecular aberrations occur within the Wnt/beta-catenin pathway (APC and beta-catenin gene mutations). Transforming growth factor-beta (TGF-beta) and connective tissue growth factor (CTGF) are profibrotic growth factors, downstream from nuclear translocation of beta-catenin, that lead to increased fibrogenesis. CTGF (a downstream effector of TGF-beta) is a matricellular protein that modulates the activity of growth factors, adhesion molecules, integrins, and extracellular matrix thus playing a central role in tissue remodeling and fibrosis. Recently there has been growing interest in use of extracellular matrix inhibitors for treatment of various fibrogenic diseases. Desmoid fibromatosis samples (n=15) were evaluated for expression of beta-catenin, TGF-beta, and CTGF using immunohistochemistry on formalin paraffin-embedded material. A control group comprising scar tissue and adjacent normal skin (n=10) were simultaneously immunostained with above mentioned markers. Real-time polymerase chain reaction was performed on frozen specimens of desmoid fibromatosis (n=6) and normal skin (n=2). All 15 desmoid tumors were positive for beta-catenin (surrogate marker of Wnt/beta-catenin pathway dysregulation) which was negative in control normal skin and scar samples. TGF-beta and CTGF were negative in 9 of 10 normal skin controls. TGF-beta and CTGF were positive in all cases of scar tissue. All 15 cases of desmoid tumors were positive for TGF-beta and CTGF. The real-time polymerase chain reaction showed higher expression levels of TGF-beta and CTGF in desmoid fibromatosis compared with normal skin. The high constitutive expression of beta-catenin downstream effectors; TGF-beta, CTGF has the potential for enabling targeted therapy. PMID- 26894650 TI - Mesothelin Expression in Advanced Gastroesophageal Cancer Represents a Novel Target for Immunotherapy. AB - The identification of new therapeutic targets is of profound importance if we are to improve outcomes in gastroesophageal cancer. This study assessed the rate of mesothelin expression in tumors of western patients with upper gastrointestinal tract carcinomas. In addition, the AGS gastric cancer cell line was tested for sensitivity to SS1(dsFv)PE38, a mesothelin-targeting immunotoxin. Previously constructed tissue microarrays containing samples from 127 patients with gastroesophageal adenocarcinomas were examined by immunohistochemistry (IHC) for mesothelin expression. Labeling for HER2-neu, E-cadherin, and c-met were also assessed. Tumors were considered positive for mesothelin if at least moderate cytoplasmic/membranous or luminal staining was present in minimum 10% of the neoplastic cells. The AGS gastric cancer cell line was assessed for surface mesothelin expression by flow cytometry and the viability of cells treated with SS1P was measured. Gastroesophageal cancers were mesothelin positive in 64 of 127 tumors [50.4%; 95% confidence interval (CI), 41.4%-59.4%], whereas only 9 carcinomas (7.1%; 95% CI, 3.3%-13.0%) were HER2-neu IHC 3+ positive and 8 (6.6%; 95% CI, 2.9%-12.5%) were c-met positive. Mesothelin expression increased from stage I to stage IV tumors (37.5% to 56.3%, respectively, P=0.10). The AGS gastric cancer cell line was sensitive to the immunotoxin with an EC50 value in the low picomolar range (0.4 ng/mL). A gastric cancer cell line derived from a western patient was exquisitely sensitive to the mesothelin-targeted immunotoxin SS1P. Clinical trials involving novel mesothelin targeted immunotherapeutics in gastroesophageal cancer are currently in development. PMID- 26894651 TI - A candidate gene approach of the calcineurin pathway to identify variants associated with clinical outcomes in renal transplantation. AB - AIM: To investigate the potential influence of variants in genes involved in the calcineurin pathway on the efficacy and toxicity of calcineurin inhibitors in renal transplantation. MATERIALS & METHODS: Twenty-three polymorphisms in thirteen genes were tested in 381 renal transplant recipients receiving ciclosporin (n = 221) or tacrolimus (n = 160) and mycophenolate mofetil. Data were collected prospectively over the first year post-transplantation. RESULTS: Multivariate survival analyses revealed no genetic associations with biopsy proven acute graft rejection and serious infections. Donor-recipient Cytomegalovirus mismatch was the only variable associated with serious infection. CONCLUSION: This large exploratory study casts doubts on the potential interest of genetic biomarkers related to CNI pharmacodynamics but associations with other phenotypes in transplantation deserve further studies. PMID- 26894652 TI - Intraretinal cystoid spaces in a patient with retinitis pigmentosa due to mutation in the MAK gene. AB - BACKGROUND: Cystoid macular edema (CME) and non-leaking intraretinal cystoid spaces (ICS) have different pathophysiologic mechanisms. MATERIALS AND METHODS: We report a patient with retinitis pigmentosa (RP) with ICS due to a mutation in the male germ cell-associated kinase (MAK) gene. RESULTS: A 41-year-old Ashkenazi Jewish male was referred for abnormal visual field revealed by regular optometric examination. His visual acuity was 20/20 in each eye. Dilated examination revealed typical finding of RP. Optical coherence tomography showed cystoid changes in each fovea. Photoreceptors were also degenerated. Intravenous fluorescein angiography showed no leakage. Genetic testing identified a homozygous mutation in the MAK gene: a 353-bp Alu insertion (K429insAlu). CONCLUSIONS: Mak regulates microtubule stability via phosphorylating RP1. Abnormal Mak may impact retinal photoreceptor ciliary length and subcompartmentalization. Mak is required for the survival of photoreceptors in mice. ICS has been reported in other ciliopathies. We report the first case of ICS due to mutation in MAK. PMID- 26894653 TI - Impact of Febuxostat on Renal Function in Gout Patients With Moderate-to-Severe Renal Impairment. AB - OBJECTIVE: Renal impairment is a risk factor for gout and a barrier to optimal gout management. We undertook this exploratory study to obtain data that have been heretofore limited regarding the safety and efficacy of febuxostat in patients with moderate-to-severe renal impairment (estimated glomerular filtration rate [GFR] 15-50 ml/minute/1.73 m(2) ). METHODS: Ninety-six gout patients with moderate-to-severe renal impairment were enrolled in a 12-month multicenter, randomized, double-blind, placebo-controlled study. Patients were randomly assigned at a 1:1:1 ratio to receive 30 mg febuxostat twice daily, 40/80 mg febuxostat once daily, or placebo. The primary efficacy end point was the change in serum creatinine (Cr) level from baseline to month 12. Secondary end points included the change in estimated GFR from baseline to month 12 and the proportion of patients with a serum uric acid (UA) level of <6.0 mg/dl at month 12. RESULTS: At month 12, there were no significant differences in the change in serum Cr level from baseline, or in the change in estimated GFR from baseline, in either febuxostat group compared to the placebo group. The proportion of patients with a serum UA level of <6.0 mg/dl at month 12 was significantly greater in both febuxostat groups compared to the placebo group (both P < 0.001). At least 1 treatment-emergent adverse event (TEAE) occurred in 78.1% of patients receiving 30 mg febuxostat twice daily, 87.5% of patients receiving 40/80 mg febuxostat once daily, and 78.1% of patients receiving placebo. TEAEs most frequently involved the categories of renal failure and impairment and renal function analyses. CONCLUSION: Febuxostat proved to be efficacious in serum UA reduction and was well tolerated in gout patients with moderate-to-severe renal impairment. Patients randomly assigned to receive febuxostat demonstrated significantly lower serum UA levels and no significant deterioration in renal function. PMID- 26894654 TI - Keloids and Hypertrophic Scars: A Spectrum of Clinical Challenges. AB - Since their earliest description, keloids and hypertrophic scars have beleaguered patients and clinicians alike. These scars can be aesthetically disfiguring, functionally debilitating, emotionally distressing, and psychologically damaging, culminating in a significant burden for patients. Our current understanding of keloid pathophysiology has grown and continues to advance while molecular biology, genetics, and technology provide ever-deepening insight into the nature of wound healing and the pathologic perturbations thereof. Greater understanding will lead to the development and application of refined therapeutic modalities. This article provides an overview of our current understanding of keloids, highlighting clinical characteristics and diagnostic criteria while providing a comprehensive summary of the many therapeutic modalities available. The proposed mechanism, application, adverse events, and reported efficacy of each modality is evaluated, and current recommendations are summarized. PMID- 26894655 TI - Withanolide Structural Revisions by (13)C NMR Spectroscopic Analysis Inclusive of the gamma-Gauche Effect. AB - A classic withanolide is defined as a highly oxygenated C28 ergostane-type steroid that is characterized by a C22-hydroxy-C26-oic acid delta-lactone in the nine-carbon side chain. Analysis of the reported (13)C NMR data of classic withanolides with hydroxy groups (C-14, C-17, and C-20) revealed that (1) a hydroxy (C-14 or C-17) substituent significantly alters the chemical shifts (C-7, C-9, C-12, and C-21) via the gamma-gauche effect; (2) the chemical shift values (C-9, C-12, and C-21) reflect the orientation (alpha or beta) of the hydroxy moiety (C-14 or C-17); (3) a double-bond positional change in ring A (Delta(2) to Delta(3)), or hydroxylation (C-27), results in a minuscule effect on the chemical shifts of carbons in rings C and D (from C-12 to C-18); and (4) the (13)C NMR gamma-gauche effect method is more convenient and reliable than the traditional approach ((1)H NMR shift comparisons in C5D5N versus CDCl3) to probe the orientation of the hydroxy substituent (C-14 and C-17). Utilization of these rules demonstrated that the reported (13)C NMR data of withanolides 1a-29a were inconsistent with their published structures, which were subsequently revised as 1-16 and 12 and 18-29, respectively. When combined, this strongly supports the application of these methods to determine the relative configuration of steroidal substituents. PMID- 26894657 TI - Transcultural Adaptation of Questionnaire to Evaluate Drug Use Among Students: The Use of the EU-Dap European Questionnaire in Brazil. AB - BACKGROUND: Social and cultural differences between countries stress the need for adapting existent instruments for adequately comparing epidemiological results. However, there are controversies in literature on how to carry out this process. OBJECTIVES: This study aimed to describe the process of cultural adaptation and evaluation of the Brazilian Portuguese language of the European Drug Addiction Prevention Trial (EU-Dap) questionnaire to identify alcohol, tobacco, and other drug use among adolescents. METHODS: The cross-sectional study took place in 16 public schools in three Brazilian cities during the year 2013 in a sample of 2,969 adolescents between the ages of 11 and 16. Operating steps involved analysis of qualitative data collected through student's focus group and field notes by interviewers and quantitative data from test-retest evaluation and nonresponse to item. RESULTS: The results revealed moderate reliability for the primary outcomes and high levels of nonresponse, mainly in the 2/3 final questions. Focus group provided high-quality information about misconception for the semantic and structure of the questionnaire. Participatory observation helped researchers to tap into the main difficulties of the application context. CONCLUSIONS: Sociocultural issues related to Brazilian students, the application context, and the structure of the original questionnaire contributed to the unsatisfactory results of the transcultural adaptation process. The results further highlighted the challenge of adapt questionnaires investigating sensitive issues in an age group particularly influenced by educational factors, especially when the countries have different standards of achievement in education. PMID- 26894658 TI - Intimate partner violence screening and counseling in the health care setting: Perception of provider-based discussions as a strategic response to IPV. AB - Intimate partner violence (IPV) affects women worldwide, and is addressable in the health care setting not only via screening, but also through provider-based counseling and referral to legal or social services, as appropriate. We conducted a study in Pennsylvania (USA) examining factors associated with receipt of IPV screening and women's perceptions of counseling discussions as a strategic response. We found that women with past-year IPV were more likely to receive screening (aOR: 2.0, 95%CI: 1.2,3.5) and to consider counseling discussions to be a strategic response to IPV exposure (aOR: 2.7, 95%CI: 1.008,7.2) than women with a more distant history of IPV. Scholars and clinicians may learn that, especially for women with a recent history of IPV, screening may provide a conduit to meaningful counseling discussions and referrals that women view as a helpful strategy in responding to IPV. PMID- 26894659 TI - Neurobiological background of borderline personality disorder, PTSD and ADHD. PMID- 26894660 TI - Reconstruction of medial patello-femoral ligament: Comparison of two surgical techniques. AB - The medial patello-femoral ligament is considered the most important passive patellar stabilizer and its proper functionality is essential for the patello femoral joint stability. In this work, 18 human knees were randomly divided into two groups and reconstructed through two different surgical techniques: the "Through tunnel tendon" and the "Double converging tunnel" reconstructions. Subsequently, the samples were mechanically tested to evaluate the structural properties of reconstructed femur-MPFL-Patella complex (rFMPC). Particular attention was given to maintain the anatomical orientation between the patella and the graft. Both procedures showed lower stiffness and higher ultimate strain and absorbed energy compared to the native MPFL, but the advantages of the double converging tunnel technique are related to the restoration of the native MPFL sail-shape, to a better stress distribution on the patella, to the use of a single interference screw as fixation device and to the simplicity, rapidity and cost-effectivity of the surgical procedure. The evaluation of the structural properties of rMPFL is fundamental to evaluate the adequacy of the different techniques to restore the physiological structural properties of the native MPFL. PMID- 26894661 TI - Fracture behavior of inlay and onlay fixed partial dentures - An in-vitro experimental and XFEM modeling study. AB - OBJECTIVES: This study aimed to explore the "sensitivity" of the fracture load and initiation site to loading position on the central occlusal surface of a pontic tooth for both all-ceramic inlay retained and onlay supported partial denture systems. MATERIALS AND METHODS: Three dimensional (3D) finite element (FE) inlay retained and onlay supported partial denture models were established for simulating crack initiation and propagation by using the eXtended Finite Element Method (XFEM). The models were subjected to a mastication force up to 500N on the central fossa of the pontic. The loading position was varied to investigate its influence on fracture load and crack path. RESULTS: Small perturbation of the loading position caused the fracture load and crack pattern to vary considerably. For the inlay fixed partial dentures (FPDs), the fracture origins changed from the bucco-gingival aspect of the molar embrasure to the premolar embrasure when the indenter force location is slightly shifted from the mesial to distal side. In contrast, for onlay FPDs, cracking initiated from bucco gingival aspect of the premolar embrasure when the indenter is slightly shifted to the buccal side and from molar embrasure when the indenter is shifted to the lingual side. CONCLUSIONS: The fracture load and cracking path were found to be very sensitive to loading position in the all-ceramic inlay and onlay FPDs. The study provides a basis for improved understanding on the role of localized contact loading of the cusp surface in all-ceramic FPDs. PMID- 26894663 TI - Enantio- and Diastereoselective Synthesis of exo-Peroxyacetals: An Organocatalyzed Peroxyhemiacetalization/oxa-Michael Addition Cascade. AB - An unprecedented enantioselective peroxyhemiacetalization/oxa-Michael addition cascade of ortho-formyl homochalcones has been developed using cinchona-alkaloid based chiral bifunctional organocatalysts to provide cis-configured exo peroxyacetals, a new class of organic peroxide, in good yields with excellent enantio- and diastereoselectivities. The resulting cis-configured exo peroxyacetals were converted into the corresponding trans-configured peroxyacetals without affecting the enantioselectivity. Furthermore, the displacement of the peroxide moiety of exo-peroxyacetals with various nucleophiles has been demonstrated to afford 1,3-disubstituted isochromans with high diastereoselectivities and excellent enantioselectivities. PMID- 26894662 TI - Coordination of Actin- and Microtubule-Based Cytoskeletons Supports Transport of Spermatids and Residual Bodies/Phagosomes During Spermatogenesis in the Rat Testis. AB - Germ cell transport across the seminiferous epithelium during spermatogenesis requires the intricate coordination of cell junctions, signaling proteins, and both actin- and microtubule (MT)-based cytoskeletons. Although the involvement of cytoskeletons in germ cell transport has been suggested, the precise mechanism(s) remains elusive. Based on growing evidence that actin and MT interactions underlie fundamental cellular processes, such as cell motility, it is unlikely that actin- and MT-based cytoskeletons work independently to regulate germ cell transport in the testis. Using rats treated with adjudin, a potential male contraceptive that disrupts spermatid adhesion and transport in the testis, as a study model, we show herein that actin- and MT-based cytoskeletons are both necessary for transport of spermatids and residual bodies/phagosomes across the seminiferous epithelium in adult rat testes. Analysis of intratubular expression of F-actin and tubulin revealed disruption of both actin and MT networks, concomitant with misdirected spermatids and phagosomes in rats treated with adjudin. Actin regulatory proteins, epidermal growth factor receptor pathway substrate 8 and actin-related protein 3, were mislocalized and down-regulated at the actin-rich anchoring junction between germ and Sertoli cells (apical ectoplasmic specialization) after adjudin treatment. Nonreceptor tyrosine kinase p-FAK-Tyr(407), known to regulate F-actin nucleation via actin-related protein 3, was also mislocalized and down-regulated at the apical ectoplasmic specialization, corroborating the observation of actin cytoskeleton disruption. Additionally, spatiotemporal expression of MT regulatory protein end-binding protein 1, shown to be involved in MT-actin cross talk herein, was also disrupted after adjudin treatment. In summary, spermatid/phagosome transport across the epithelium during spermatogenesis requires the coordination between actin- and MT based cytoskeletons. PMID- 26894664 TI - Predictive value of general movements' quality in low-risk infants for minor neurological dysfunction and behavioural problems at preschool age. AB - BACKGROUND: General movement (GM) assessment is a well-established tool to predict cerebral palsy in high-risk infants. Little is known on the predictive value of GM assessment in low-risk populations. AIMS: To assess the predictive value of GM quality in early infancy for the development of the clinically relevant form of minor neurological dysfunction (complex MND) and behavioral problems at preschool age. STUDY DESIGN: Prospective cohort study. SUBJECTS: A total of 216 members of the prospective Groningen Assisted Reproductive Techniques (ART) cohort study were included in this study. ART did not affect neurodevelopmental outcome of these relatively low-risk infants born to subfertile parents. OUTCOME MEASURES: GM quality was determined at 2 weeks and 3 months. At 18 months and 4 years, the Hempel neurological examination was used to assess MND. At 4 years, parents completed the Child Behavior Checklist; this resulted in the total problem score (TPS), internalizing problem score (IPS), and externalizing problem score (EPS). Predictive values of definitely (DA) and mildly (MA) abnormal GMs were calculated. RESULTS: DA GMs at 2 weeks were associated with complex MND at 18 months and atypical TPS and IPS at 4 years (all p<0.05). Sensitivity and positive predictive value of DA GMs at 2 weeks were rather low (13%-60%); specificity and negative predictive value were excellent (92%-99%). DA GMs at 3 months occurred too infrequently to calculate prediction. MA GMs were not associated with outcome. CONCLUSIONS: GM quality as a single predictor for complex MND and behavioral problems at preschool age has limited clinical value in children at low risk for developmental disorders. PMID- 26894665 TI - Very low birth weight infant care: adherence to a new nutrition protocol improves growth outcomes and reduces infectious risk. AB - BACKGROUND: Very low birth weight (VLBW) infants are at risk for postnatal growth restriction due to inadequate nutrient delivery and concomitant illness. Integrated clinical pathways or protocols can improve growth outcomes by decreasing practice variability. METHODS: A comprehensive nutrition bundle comprising standardized recommendations for initiating, advancing, and fortifying enteral feedings, and timely discontinuation of central lines was implemented in July 2012. Eligible were infants with a birth weight of <1500 g and <34 weeks gestation who were born over a 1-year period pre- and post-intervention, respectively. The primary aim was to determine if the intervention improved anthropometric parameter delta z scores at 36 weeks PMA. Secondary aims included time to first and full enteral feedings, central line-days, and rates of necrotizing enterocolitis (NEC) and sepsis/sepsis-like episodes. RESULTS: A total of 299 infants were included, of which 156 received the proposed intervention (Nutrition bundle group), and 143 received non-standardized nutrition practices (Conventional group). Median delta z scores for length (-1.2 versus -1.71; p=0.01) and head circumference (-0.73 versus -1.21; p=0.03) but not weight at 36 weeks PMA (-1.42 versus -1.58; p=0.74) were significantly higher in the Nutrition bundle group as compared to the Conventional group. Fewer infants in the intervention group had severe growth restriction. Time to first feed, full feeds, and central line duration were significantly shorter in the intervention period. The incidence of NEC and sepsis/sepsis-like episodes decreased with the intervention. CONCLUSIONS: A strategy using a comprehensive nutrition bundle improved linear and head circumference growth, reduced postnatal growth restriction, and decreased comorbidities in VLBW infants. PMID- 26894666 TI - Combining cross-crystal averaging and MRSAD to phase a 4354-amino-acid structure. AB - The B and C proteins from the ABC toxin complex of Yersinia entomophaga form a large heterodimer that cleaves and encapsulates the C-terminal toxin domain of the C protein. Determining the structure of the complex formed by B and the N terminal region of C was challenging owing to its large size, the non-isomorphism of different crystals and their sensitivity to radiation damage. A native data set was collected to 2.5 A resolution and a non-isomorphous Ta6Br12-derivative data set was collected that showed strong anomalous signal at low resolution. The tantalum-cluster sites could be found, but the anomalous signal did not extend to a high enough resolution to allow model building. Selenomethionine (SeMet) derivatized protein crystals were produced, but the high number (60) of SeMet sites and the sensitivity of the crystals to radiation damage made phasing using the SAD or MAD methods difficult. Multiple SeMet data sets were combined to provide 30-fold multiplicity, and the low-resolution phase information from the Ta6Br12 data set was transferred to this combined data set by cross-crystal averaging. This allowed the Se atoms to be located in an anomalous difference Fourier map; they were then used in Auto-Rickshaw for multiple rounds of autobuilding and MRSAD. PMID- 26894667 TI - Structural characterization of the N-terminal part of the MERS-CoV nucleocapsid by X-ray diffraction and small-angle X-ray scattering. AB - The N protein of coronaviruses is a multifunctional protein that is organized into several domains. The N-terminal part is composed of an intrinsically disordered region (IDR) followed by a structured domain called the N-terminal domain (NTD). In this study, the structure determination of the N-terminal region of the MERS-CoV N protein via X-ray diffraction measurements is reported at a resolution of 2.4 A. Since the first 30 amino acids were not resolved by X-ray diffraction, the structural study was completed by a SAXS experiment to propose a structural model including the IDR. This model presents the N-terminal region of the MERS-CoV as a monomer that displays structural features in common with other coronavirus NTDs. PMID- 26894668 TI - Concerted action of two subunits of the functional dimer of Shewanella oneidensis MR-1 uridine phosphorylase derived from a comparison of the C212S mutant and the wild-type enzyme. AB - Uridine phosphorylase (UP; EC 2.4.2.3), a key enzyme in the pyrimidine-salvage pathway, catalyzes the reversible phosphorolysis of uridine to uracil and ribose 1-phosphate. The structure of the C212S mutant of uridine phosphorylase from the facultatively aerobic Gram-negative gamma-proteobacterium Shewanella oneidensis MR-1 (SoUP) was determined at 1.68 A resolution. A comparison of the structures of the mutant and the wild-type enzyme showed that one dimer in the mutant hexamer differs from all other dimers in the mutant and wild-type SoUP (both in the free form and in complex with uridine). The key difference is the 'maximum open' state of one of the subunits comprising this dimer, which has not been observed previously for uridine phosphorylases. Some conformational features of the SoUP dimer that provide access of the substrate into the active site are revealed. The binding of the substrate was shown to require the concerted action of two subunits of the dimer. The changes in the three-dimensional structure induced by the C212S mutation account for the lower affinity of the mutant for inorganic phosphate, while the affinity for uridine remains unchanged. PMID- 26894669 TI - Atomic resolution structure of a chimeric DNA-RNA Z-type duplex in complex with Ba(2+) ions: a case of complicated multi-domain twinning. AB - The self-complementary dCrGdCrGdCrG hexanucleotide, in which not only the pyrimidine/purine bases but also the ribo/deoxy sugars alternate along the sequence, was crystallized in the presence of barium cations in the form of a left-handed Z-type duplex. The asymmetric unit of the P21 crystal with a pseudohexagonal lattice contains four chimeric duplexes and 16 partial Ba(2+) sites. The chimeric (DNA-RNA)2 duplexes have novel patterns of hydration and exhibit a high degree of discrete conformational disorder of their sugar phosphate backbones, which can at least partly be correlated with the fractional occupancies of the barium ions. The crystals of the DNA-RNA chimeric duplex in complex with Ba(2+) ions and also with Sr(2+) ions exhibit complicated twinning, which in combination with structural pseudosymmetry made structure determination difficult. The structure could be successfully solved by molecular replacement in space groups P1 and P21 but not in orthorhombic or higher symmetry and, after scrupulous twinning and packing analysis, was refined in space group P21 to an R and Rfree of 11.36 and 16.91%, respectively, using data extending to 1.09 A resolution. With the crystal structure having monoclinic symmetry, the sixfold crystal twinning is a combination of threefold and twofold rotations. The paper describes the practical aspects of dealing with cases of complicated twinning and pseudosymmetry, and compares the available software tools for the refinement and analysis of such cases. PMID- 26894670 TI - Lessons from ten years of crystallization experiments at the SGC. AB - Although protein crystallization is generally considered more art than science and remains significantly trial-and-error, large-scale data sets hold the promise of providing general learning. Observations are presented here from retrospective analyses of the strategies actively deployed for the extensive crystallization experiments at the Oxford site of the Structural Genomics Consortium (SGC), where comprehensive annotations by SGC scientists were recorded on a customized database infrastructure. The results point to the importance of using redundancy in crystallizing conditions, specifically by varying the mixing ratios of protein sample and precipitant, as well as incubation temperatures. No meaningful difference in performance could be identified between the four most widely used sparse-matrix screens, judged by the yield of crystals leading to deposited structures; this suggests that in general any comparison of screens will be meaningless without extensive cross-testing. Where protein sample is limiting, exploring more conditions has a higher likelihood of being informative by yielding hits than does redundancy of either mixing ratio or temperature. Finally, on the logistical question of how long experiments should be stored, 98% of all crystals that led to deposited structures appeared within 30 days. Overall, these analyses serve as practical guidelines for the design of initial screening experiments for new crystallization targets. PMID- 26894671 TI - Structural basis for the interaction of BamB with the POTRA3-4 domains of BamA. AB - In Escherichia coli, the Omp85 protein BamA and four lipoproteins (BamBCDE) constitute the BAM complex, which is essential for the assembly and insertion of outer membrane proteins into the outer membrane. Here, the crystal structure of BamB in complex with the POTRA3-4 domains of BamA is reported at 2.1 A resolution. Based on this structure, the POTRA3 domain is associated with BamB via hydrogen-bonding and hydrophobic interactions. Structural and biochemical analysis revealed that the conserved residues Arg77, Glu127, Glu150, Ser167, Leu192, Leu194 and Arg195 of BamB play an essential role in interaction with the POTRA3 domain. PMID- 26894672 TI - The cap-binding site of influenza virus protein PB2 as a drug target. AB - The RNA polymerase of influenza virus consists of three subunits: PA, PB1 and PB2. It uses a unique 'cap-snatching' mechanism for the transcription of viral mRNAs. The cap-binding domain of the PB2 subunit (PB2cap) in the viral polymerase binds the cap of a host pre-mRNA molecule, while the endonuclease of the PA subunit cleaves the RNA 10-13 nucleotides downstream from the cap. The capped RNA fragment is then used as the primer for viral mRNA transcription. The structure of PB2cap from influenza virus H1N1 A/California/07/2009 and of its complex with the cap analog m(7)GTP were solved at high resolution. Structural changes are observed in the cap-binding site of this new pandemic influenza virus strain, especially the hydrophobic interactions between the ligand and the target protein. m(7)GTP binds deeper in the pocket than some other virus strains, much deeper than the host cap-binding proteins. Analysis of the new H1N1 structures and comparisons with other structures provide new insights into the design of small-molecule inhibitors that will be effective against multiple strains of both type A and type B influenza viruses. PMID- 26894673 TI - Three-dimensional structures of two heavily N-glycosylated Aspergillus sp. family GH3 beta-D-glucosidases. AB - The industrial conversion of cellulosic plant biomass into useful products such as biofuels is a major societal goal. These technologies harness diverse plant degrading enzymes, classical exo- and endo-acting cellulases and, increasingly, cellulose-active lytic polysaccharide monooxygenases, to deconstruct the recalcitrant beta-D-linked polysaccharide. A major drawback with this process is that the exo-acting cellobiohydrolases suffer from severe inhibition from their cellobiose product. beta-D-Glucosidases are therefore important for liberating glucose from cellobiose and thereby relieving limiting product inhibition. Here, the three-dimensional structures of two industrially important family GH3 beta-D glucosidases from Aspergillus fumigatus and A. oryzae, solved by molecular replacement and refined at 1.95 A resolution, are reported. Both enzymes, which share 78% sequence identity, display a three-domain structure with the catalytic domain at the interface, as originally shown for barley beta-D-glucan exohydrolase, the first three-dimensional structure solved from glycoside hydrolase family GH3. Both enzymes show extensive N-glycosylation, with only a few external sites being truncated to a single GlcNAc molecule. Those glycans N linked to the core of the structure are identified purely as high-mannose trees, and establish multiple hydrogen bonds between their sugar components and adjacent protein side chains. The extensive glycans pose special problems for crystallographic refinement, and new techniques and protocols were developed especially for this work. These protocols ensured that all of the D-pyranosides in the glycosylation trees were modelled in the preferred minimum-energy (4)C1 chair conformation and should be of general application to refinements of other crystal structures containing O- or N-glycosylation. The Aspergillus GH3 structures, in light of other recent three-dimensional structures, provide insight into fungal beta-D-glucosidases and provide a platform on which to inform and inspire new generations of variant enzymes for industrial application. PMID- 26894674 TI - Fitmunk: improving protein structures by accurate, automatic modeling of side chain conformations. AB - Improvements in crystallographic hardware and software have allowed automated structure-solution pipelines to approach a near-'one-click' experience for the initial determination of macromolecular structures. However, in many cases the resulting initial model requires a laborious, iterative process of refinement and validation. A new method has been developed for the automatic modeling of side chain conformations that takes advantage of rotamer-prediction methods in a crystallographic context. The algorithm, which is based on deterministic dead-end elimination (DEE) theory, uses new dense conformer libraries and a hybrid energy function derived from experimental data and prior information about rotamer frequencies to find the optimal conformation of each side chain. In contrast to existing methods, which incorporate the electron-density term into protein modeling frameworks, the proposed algorithm is designed to take advantage of the highly discriminatory nature of electron-density maps. This method has been implemented in the program Fitmunk, which uses extensive conformational sampling. This improves the accuracy of the modeling and makes it a versatile tool for crystallographic model building, refinement and validation. Fitmunk was extensively tested on over 115 new structures, as well as a subset of 1100 structures from the PDB. It is demonstrated that the ability of Fitmunk to model more than 95% of side chains accurately is beneficial for improving the quality of crystallographic protein models, especially at medium and low resolutions. Fitmunk can be used for model validation of existing structures and as a tool to assess whether side chains are modeled optimally or could be better fitted into electron density. Fitmunk is available as a web service at http://kniahini.med.virginia.edu/fitmunk/server/ or at http://fitmunk.bitbucket.org/. PMID- 26894675 TI - Structural elucidation of the NADP(H) phosphatase activity of staphylococcal dual specific IMPase/NADP(H) phosphatase. AB - NADP(H)/NAD(H) homeostasis has long been identified to play a pivotal role in the mitigation of reactive oxygen stress (ROS) in the intracellular milieu and is therefore critical for the progression and pathogenesis of many diseases. NAD(H) kinases and NADP(H) phosphatases are two key players in this pathway. Despite structural evidence demonstrating the existence and mode of action of NAD(H) kinases, the specific annotation and the mode of action of NADP(H) phosphatases remains obscure. Here, structural evidence supporting the alternative role of inositol monophosphatase (IMPase) as an NADP(H) phosphatase is reported. Crystal structures of staphylococcal dual-specific IMPase/NADP(H) phosphatase (SaIMPase I) in complex with the substrates D-myo-inositol-1-phosphate and NADP(+) have been solved. The structure of the SaIMPase-I-Ca(2+)-NADP(+) ternary complex reveals the catalytic mode of action of NADP(H) phosphatase. Moreover, structures of SaIMPase-I-Ca(2+)-substrate complexes have reinforced the earlier proposal that the length of the active-site-distant helix alpha4 and its preceding loop are the predisposing factors for the promiscuous substrate specificity of SaIMPase-I. Altogether, the evidence presented suggests that IMPase-family enzymes with a shorter alpha4 helix could be potential candidates for previously unreported NADP(H) phosphatase activity. PMID- 26894676 TI - Efficacy of novel synthetic bone substitutes in the reconstruction of large segmental bone defects in sheep tibiae. AB - The treatment of large bone defects, particularly those with segmental bone loss, remains a significant clinical challenge as current approaches involving surgery or bone grafting often do not yield satisfactory long-term outcomes. This study reports the evaluation of novel ceramic scaffolds applied as bone graft substitutes in a clinically relevant in vivo model. Baghdadite scaffolds, unmodified or modified with a polycaprolactone coating containing bioactive glass nanoparticles, were implanted into critical-sized segmental bone defects in sheep tibiae for 26 weeks. Radiographic, biomechanical, MU-CT and histological analyses showed that both unmodified and modified baghdadite scaffolds were able to withstand physiological loads at the defect site, and induced substantial bone formation in the absence of supplementation with cells or growth factors. Notably, all samples showed significant bridging of the critical-sized defect (average 80%) with evidence of bone infiltration and remodelling within the scaffold implant. The unmodified and modified baghdadite scaffolds achieved similar outcomes of defect repair, although the latter may have an initial mechanical advantage due to the nanocomposite coating. The baghdadite scaffolds evaluated in this study hold potential for use as purely synthetic bone graft substitutes in the treatment of large bone defects while circumventing the drawbacks of autografts and allografts. PMID- 26894677 TI - Comparative study on DBPs formation profiles of intermediate organics from hydroxyl radicals oxidation of microbial cells. AB - This study assessed the characteristics of disinfection byproducts (DBPs) formation from intermediate organics during UV/H2O2 treatment of activated sludge and algae cells under various reaction conditions. The DBPs including trihalomethanes (THMs), haloacetic acids (HAAs), haloketones (HKs) and haloacetonitriles (HANs) in UV/H2O2-treated and chlorinated water were measured. The results showed that both dissolved organic carbon (DOC) and dissolved organic nitrogen (DON) increased during the initial stage of UV/H2O2 treatment due to the lysis of sludge and algae cells, which enhanced the formation of both C- and N DBPs; however, both DOC and DON decreased after longer reaction times. During the UV/H2O2 treatments, THMs formation potential (THMFP) peaked earlier than did HAAs formation potential (HAAFP). This shows that the dissolved organics released from lysis of microbial cells in the early stages of oxidation favor the production of THMs over HAAs; however, HAAs precursors increased with the oxidation time. Chlorination with bromide increased the formation of THMs and HAAs but less HKs and HANs were produced. Comparisons of normalized DBP formation potential (DBPFP) of samples collected during UV/H2O2 treatments of four different types of organic matter showed that the highest DBPFP occurred in filtered treated wastewater effluent, followed by samples of activated sludge, filtered eutrophicated pond water, and samples of algae cells. With increasing oxidation time, the dominant DBP species shifted from THMs to HAAs in the samples of activated sludge and algae cells. The DBPFP tests also showed that more HAAs were formed in biologically treated wastewater effluent, while the eutrophicated source water produced more THMs. PMID- 26894678 TI - Use of neutralized industrial residue to stabilize trace elements (Cu, Cd, Zn, As, Mo, and Cr) in marine dredged sediment from South-East of France. AB - Management of marine dredged sediments polluted with trace elements is prime issue in the French Mediterranean coast. The polluted sediments possess ecological threats to surrounding environment on land disposal. Therefore, stabilization of contaminants in multi-contaminated marine dredged sediment is a promising technique. Present study aimed to assess the effect of gypsum neutralized bauxaline((r)) (bauxite residue) to decrease the availability of pollutants and inherent toxicity of marine dredged sediment. Bauxaline((r)), (alumia industry waste) contains high content of iron oxide but its high alkalinity makes it not suitable for the stabilization of all trace elements from multi-contaminated dredged sediments. In this study, neutralized bauxaline((r)) was prepared by mixing bauxaline((r)) with 5% of plaster. Experiments were carried out for 3 months to study the effect of 5% and 20% amendment rate on the availability of Cu, Cd, Zn, As, Mo, and Cr. Trace elements concentration, pH, EC and dissolved organic carbon were measured in all leachates. Toxicity of leachates was assessed against marine rotifers Brachionus plicatilis. The Results showed that both treatments have immobilization capacity against different pollutants. Significant stabilization of contaminants (Cu, Cd, Zn) was achieved with 20% application rate whereas As, Mo, and Cr were slightly stabilized. Toxicity results revealed that leachates collected from treated sediment were less toxic than the control sediment. These results suggest that application of neutralized bauxaline((r)) to dredged sediment is an effective approach to manage large quantities of dredged sediments as well as bauxite residue itself. PMID- 26894680 TI - Did you or I say pretty, rude or brief? An ERP study of the effects of speaker's identity on emotional word processing. AB - During speech comprehension, multiple cues need to be integrated at a millisecond speed, including semantic information, as well as voice identity and affect cues. A processing advantage has been demonstrated for self-related stimuli when compared with non-self stimuli, and for emotional relative to neutral stimuli. However, very few studies investigated self-other speech discrimination and, in particular, how emotional valence and voice identity interactively modulate speech processing. In the present study we probed how the processing of words' semantic valence is modulated by speaker's identity (self vs. non-self voice). Sixteen healthy subjects listened to 420 prerecorded adjectives differing in voice identity (self vs. non-self) and semantic valence (neutral, positive and negative), while electroencephalographic data were recorded. Participants were instructed to decide whether the speech they heard was their own (self-speech condition), someone else's (non-self speech), or if they were unsure. The ERP results demonstrated interactive effects of speaker's identity and emotional valence on both early (N1, P2) and late (Late Positive Potential - LPP) processing stages: compared with non-self speech, self-speech with neutral valence elicited more negative N1 amplitude, self-speech with positive valence elicited more positive P2 amplitude, and self-speech with both positive and negative valence elicited more positive LPP. ERP differences between self and non self speech occurred in spite of similar accuracy in the recognition of both types of stimuli. Together, these findings suggest that emotion and speaker's identity interact during speech processing, in line with observations of partially dependent processing of speech and speaker information. PMID- 26894679 TI - The Development of a Recombinant scFv Monoclonal Antibody Targeting Canine CD20 for Use in Comparative Medicine. AB - Monoclonal antibodies are leading agents for therapeutic treatment of human diseases, but are limited in use by the paucity of clinically relevant models for validation. Sporadic canine tumours mimic the features of some human equivalents. Developing canine immunotherapeutics can be an approach for modeling human disease responses. Rituximab is a pioneering agent used to treat human hematological malignancies. Biologic mimics that target canine CD20 are just being developed by the biotechnology industry. Towards a comparative canine-human model system, we have developed a novel anti-CD20 monoclonal antibody (NCD1.2) that binds both human and canine CD20. NCD1.2 has a sub-nanomolar Kd as defined by an octet red binding assay. Using FACS, NCD1.2 binds to clinically derived canine cells including B-cells in peripheral blood and in different histotypes of B-cell lymphoma. Immunohistochemical staining of canine tissues indicates that the NCD1.2 binds to membrane localized cells in Diffuse Large B-cell lymphoma, Marginal Zone Lymphoma, and other canine B-cell lymphomas. We cloned the heavy and light chains of NCD1.2 from hybridomas to determine whether active scaffolds can be acquired as future biologics tools. The VH and VL genes from the hybridomas were cloned using degenerate primers and packaged as single chains (scFv) into a phage-display library. Surprisingly, we identified two scFv (scFv-3 and scFv-7) isolated from the hybridoma with bioactivity towards CD20. The two scFv had identical VH genes but different VL genes and identical CDR3s, indicating that at least two light chain mRNAs are encoded by NCD1.2 hybridoma cells. Both scFv-3 and scFv-7 were cloned into mammalian vectors for secretion in CHO cells and the antibodies were bioactive towards recombinant CD20 protein or peptide. The scFv-3 and scFv-7 were cloned into an ADEPT-CPG2 bioconjugate vector where bioactivity was retained when expressed in bacterial systems. These data identify a recombinant anti-CD20 scFv that might form a useful tool for evaluation in bioconjugate-directed anti-CD20 immunotherapies in comparative medicine. PMID- 26894682 TI - A Comprehensive Study on Lyotropic Liquid-Crystalline Behavior of an Amphiphile in 20 Kinds of Amino Acid Ionic Liquids. AB - We examined the self-organization behavior of a designed amphiphilic molecule in 20 kinds of amino acid ionic liquids composed of 1-butyl-3-methylimidazolium cation and natural amino acid anion ([C4mim][AA]). Addition of [C4mim][AA], regardless of their anion species, to the amphiphile provided homogeneous mixtures showing lyotropic liquid-crystalline (LC) behavior. Upon increasing the component ratio of [C4mim][AA] in the mixtures, a successive change of the mesophase patterns from inverted hexagonal columnar, in some case via bicontinuous cubic, to layered phases was observed. By examining the LC properties at various temperatures and component ratios, we constructed lyotropic LC phase diagrams. Interestingly, the appearance of these phase diagrams is greatly different according to the selection of [AA]. Through comparison, we found that the self-organization behavior of an amphiphile in ionic liquids can be tuned by controlling their ability to form hydrogen-bond, van der Waals, and pi-pi interactions. PMID- 26894681 TI - Analysis of the association between plasma PCSK9 and Lp(a) in Han Chinese. AB - PURPOSE: It has been reported that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors can significantly reduce lipoprotein(a) [Lp(a)], and the mechanism for Lp(a) reduction remains unclear. Recently an interesting clinical research with a small sample showed a positive correlation between plasma PCSK9 and Lp(a) levels in diabetes. Here we aimed to use a relatively large sample to investigate whether such an association exists in Han Chinese. METHODS: A total of 783 inpatients were consecutively enrolled and composed of 172 patients with type 2 diabetes mellitus (T2DM) and 611 non-T2DM subjects. Plasma PCSK9 level was measured by ELISA, and its association with Lp(a) was assayed by Spearman's correlation and multiple regression. Clinical and biochemical parameters were determined in all subjects studied. RESULTS: No significant differences in PCSK9 and Lp(a) levels were found between T2DM and non-T2DM patients. PCSK9 level was not related to Lp(a) level either in T2DM or non-T2DM group in bivariate correlation and multiple linear regression analysis. Additionally, no association between the levels of PCSK9 and Lp(a) was found in well, poorly controlled T2DM patients or in T2DM patients with or without coronary artery disease (CAD). Besides, no difference was found among the PCSK9 values across tertiles of Lp(a) level. CONCLUSION: We found no association of plasma PCSK9 levels with Lp(a) level in Han Chinese with or without T2DM, suggesting that Lp(a) reduction by PCSK9 inhibitors may not be achieved simply through PCSK9 pathway at least in Chinese. PMID- 26894683 TI - [New methods for endoscopic hemostasis: focus on non-variceal gastrointestinal bleeding]. AB - Gastrointestinal bleeding is a frequent emergency in daily clinical practice of a gastroenterologist. While incidence and mortality of gastrointestinal bleeding are decreasing in many countries, numbers of endoscopic procedures are increasing. Endoscopic therapy of non-variceal gastrointestinal bleeding is still mainly based on "classical" procedures like injection of vasoactive drugs (i. e. epinephrine) or blood derivates, application of through-the-scope hemoclips (TTSC), Argon plasma coagulation and bipolar coagulation. However, in the last years new endoscopic techniques especially for non-variceal gastrointestinal bleedings have become available and enriched our endoscopic equipment. For example, over-the-scope clips (OTSCs) surpass the size of TTSCs and have been successfully established for treatment of gastrointestinal bleeding and leak closure of fistulas and perforations. In addition, hemostatic powders were shown to achieve primary hemostasis in several cases of gastrointestinal bleeding. Besides a brief overview of "classical" endoscopic procedures for hemostasis of non-variceal gastrointestinal bleeding, this review focuses on new epidemiological data and uprising methods for endoscopic hemostasis. PMID- 26894684 TI - Targeted cofactor quantification in metabolically engineered E. coli using solid phase extraction and hydrophilic interaction liquid chromatography-mass spectrometry. AB - Quantification of energy and redox cofactors is of great value to synthetic biologists to infer the balance of energy metabolism in engineered microbial strains and assess each strain's potential for further improvement. Most currently used methods for intracellular cofactor measurement suffer from incomplete coverage, low reproducibility, suboptimal sensitivity or specificity. In this study, we described an SPE-HILIC/MS approach for simultaneous determination of six cofactor targets (ATP, ADP, NAD, NADH, NADP, NADPH) in Escherichia coli cells. Sufficient linearity, precision and metabolite recoveries of this new approach justified its reliability in targeted cofactor quantification. Our approach was then compared with conventional enzymatic assays to demonstrate its superior performance. We applied the SPE-HILIC/MS approach to profile shift of cofactor balances in several engineered E. coli strains with varying isobutanol production. Our cofactor analysis clearly revealed that optimal energy fitness was achieved in the highest-yield strain through combined modulation of a transhydrogenase and a NAD(+) kinase. Apart from the targeted cofactors, the SPE enrichment procedure also allowed for confident identification of 39 groups of polar metabolites mainly involved in central carbon metabolism in E. coli cells. PMID- 26894685 TI - Determination of valnemulin in swine and bovine tissues by ultra-high performance liquid chromatography-tandem mass spectrometry. AB - A sensitive and reliable method has been developed and validated for the determination of valnemulin in swine and bovine muscle, liver, and kidney using solid-phase extraction (SPE) and ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). The tissue samples were extracted with mixture solution of acetonitrile and 0.01mol/L hydrochloric acid, defatted by n hexane, and further cleaned up using SPE cartridges with polymeric sorbent. Gradient UHPLC separation was performed using an Acquity BEH C18 column with water and acetonitrile as the mobile phase. Multiple reaction monitoring mode of two precursor-product ion transitions for valnemulin was used. Mean recoveries from fortified samples ranged from 93.4 to 104.3% with 3.3-10.7% relative standard deviation. The limit of detection and quantification was 0.2 and 1MUg/kg for the analyte, respectively. PMID- 26894686 TI - Diagnostic Performance of First-Pass Myocardial Perfusion Imaging without Stress with Computed Tomography (CT) Compared with Coronary CT Angiography Alone, with Fractional Flow Reserve as the Reference Standard. AB - Coronary computed tomography angiography (CCTA) in combination with first-pass CT myocardial perfusion imaging (MPI) has a better diagnostic performance than CCTA alone, compared with invasive coronary angiography as the reference standard. The aim of this study was to investigate the additional diagnostic value of first pass CT-MPI without stress for detecting hemodynamic significance of coronary stenosis, compared with invasive fractional flow reserve (FFR). We recruited 53 patients with suspected coronary artery disease undergoing both CCTA and first pass CT-MPI without stress and invasive FFR, and 75 vessels were analyzed. We used the same raw data for CCTA and CT-MPI. First-pass CT-MPI was reconstructed by examining the diastolic signal densities as a bull's eye map. Invasive FFR <0.8 was considered as positive. On per-vessel analysis, the area under the receiver operating characteristic curve for CCTA plus first-pass CT-MPI and CCTA alone was 0.81 (0.73-0.90) and 0.70 (0.61-0.81), respectively (P = 0.036). CCTA plus first-pass CT-MPI without stress showed 0.73 sensitivity, 0.74 specificity, 0.53 positive predictive value, and 0.87 negative predictive value for detecting hemodynamically significant coronary stenosis. First-pass CT-MPI without stress correctly reclassified 38% of CCTA false-positive vessels as true negative. First pass CT-MPI without stress combined with CCTA demonstrated excellent diagnostic accuracy, compared with invasive FFR as the reference standard. This technique could complement CCTA for diagnosis of coronary artery disease. PMID- 26894687 TI - Water Holding as Determinant for the Elastically Stored Energy in Protein-Based Gels. AB - To evaluate the importance of the water holding capacity for the elastically stored energy of protein gels, a range of gels were created from proteins from different origin (plant: pea and soy proteins, and animal: whey, blood plasma, egg white proteins, and ovalbumin) varying in network morphology set by the protein concentration, pH, ionic strength, or the presence of specific ions. The results showed that the observed positive and linear relation between water holding (WH) and elastically stored energy (RE) is generic for globular protein gels studied. The slopes of this relation are comparable for all globular protein gels (except for soy protein gels) whereas the intercept is close to 0 for most of the systems except for ovalbumin and egg white gels. The slope and intercept obtained allows one to predict the impact of tuning WH, by gel morphology or network stiffness, on the mechanical deformation of the protein-based gel. Addition of charged polysaccharides to a protein system leads to a deviation from the linear relation between WH and RE and this deviation coincides with a change in phase behavior. PMID- 26894688 TI - Evolution of brain and culture: the neurological and cognitive journey from Australopithecus to Albert Einstein. AB - Fossil and comparative primatological evidence suggest that alterations in the development of prehistoric hominin infants kindled three consecutive evolutionary developmental (evo-devo) trends that, ultimately, paved the way for the evolution of the human brain and cognition. In the earliest trend, infants' development of posture and locomotion became delayed because of anatomical changes that accompanied the prolonged evolution of bipedalism. Because modern humans have inherited these changes, our babies are much slower than other primates to reach developmental milestones such as standing, crawling, and walking. The delay in ancestral babies' physical development eventually precipitated an evolutionary reversal in which they became increasing unable to cling independently to their mothers. For the first time in prehistory, babies were, thus, periodically deprived of direct physical contact with their mothers. This prompted the emergence of a second evo-devo trend in which infants sought contact comfort from caregivers using evolved signals, including new ways of crying that are conserved in modern babies. Such signaling stimulated intense reciprocal interactions between prehistoric mothers and infants that seeded the eventual emergence of motherese and, subsequently, protolanguage. The third trend was for an extreme acceleration in brain growth that began prior to the last trimester of gestation and continued through infants' first postnatal year (early "brain spurt"). Conservation of this trend in modern babies explains why human brains reach adult sizes that are over three times those of chimpanzees. The fossil record of hominin cranial capacities together with comparative neuroanatomical data suggest that, around 3 million years ago, early brain spurts began to facilitate an evolutionary trajectory for increasingly large adult brains in association with neurological reorganization. The prehistoric increase in brain size eventually caused parturition to become exceedingly difficult, and this difficulty, known as the "obstetrical dilemma", is likely to constrain the future evolution of brain size and, thus, privilege ongoing evolution in neurological reorganization. In modern babies, the brain spurt is accompanied by formation and tuning (pruning) of neurological connections, and development of dynamic higher-order networks that facilitate acquisition of grammatical language and, later in development, other advanced computational abilities such as musical or mathematical perception and performance. The cumulative evidence suggests that the emergence and refinement of grammatical language was a prime mover of hominin brain evolution. PMID- 26894690 TI - Rotating Flow of Magnetite-Water Nanofluid over a Stretching Surface Inspired by Non-Linear Thermal Radiation. AB - Present study explores the MHD three-dimensional rotating flow and heat transfer of ferrofluid induced by a radiative surface. The base fluid is considered as water with magnetite-Fe3O4 nanoparticles. Novel concept of non-linear radiative heat flux is considered which produces a non-linear energy equation in temperature field. Conventional transformations are employed to obtain the self similar form of the governing differential system. The arising system involves an interesting temperature ratio parameter which is an indicator of small/large temperature differences in the flow. Numerical simulations with high precision are determined by well-known shooting approach. Both uniform stretching and rotation have significant impact on the solutions. The variation in velocity components with the nanoparticle volume fraction is non-monotonic. Local Nusselt number in Fe3O4-water ferrofluid is larger in comparison to the pure fluid even at low particle concentration. PMID- 26894689 TI - Protective Effects of Ferulic Acid against Heat Stress-Induced Intestinal Epithelial Barrier Dysfunction In Vitro and In Vivo. AB - Heat stress is important in the pathogenesis of intestinal epithelial barrier dysfunction. Ferulic acid (FA), a phenolic acid widely found in fruits and vegetables, can scavenge free radicals and activate cell stress responses. This study is aimed at investigating protective effects of FA on heat stress-induced dysfunction of the intestinal epithelial barrier in vitro and in vivo. Intestinal epithelial (IEC-6) cells were pretreated with FA for 4 h and then exposed to heat stress. Heat stress caused decreased transepithelial electrical resistance (TER) and increased permeability to 4-kDa fluorescein isothiocyanate (FITC)-dextran (FD4). Both effects were inhibited by FA in a dose-dependent manner. FA significantly attenuated the decrease in occludin, ZO-1 and E-cadherin expression observed with heat stress. The distortion and redistribution of occludin, ZO-1 and E-cadherin proteins were also effectively prevented by FA pretreatment. Moreover, heat stress diminished electron-dense material detected in tight junctions (TJs), an effect also alleviated by FA in a dose-dependent manner. In an in vivo heat stress model, FA (50 mg/kg) was administered to male Sprague Dawley rats for 7 consecutive days prior to exposure to heat stress. FA pretreatment significantly attenuated the effects of heat stress on the small intestine, including the increased FD4 permeability, disrupted tight junctions and microvilli structure, and reduced occludin, ZO-1 and E-cadherin expression. Taken together, our results demonstrate that FA pretreatment is potentially protective against heat stress-induced intestinal epithelial barrier dysfunction. PMID- 26894692 TI - Photonic Maxwell's Demon. AB - We report an experimental realization of Maxwell's demon in a photonic setup. We show that a measurement at the few-photons level followed by a feed-forward operation allows the extraction of work from intense thermal light into an electric circuit. The interpretation of the experiment stimulates the derivation of an equality relating work extraction to information acquired by measurement. We derive a bound using this relation and show that it is in agreement with the experimental results. Our work puts forward photonic systems as a platform for experiments related to information in thermodynamics. PMID- 26894693 TI - Momentum-Space Correlations of a One-Dimensional Bose Gas. AB - Analyzing the noise in the momentum profiles of single realizations of one dimensional Bose gases, we present the experimental measurement of the full momentum-space density correlations ?deltan_{p}deltan_{p^{'}}?, which are related to the two-body momentum correlation function. Our data span the weakly interacting region of the phase diagram, going from the ideal Bose gas regime to the quasicondensate regime. We show experimentally that the bunching phenomenon, which manifests itself as super-Poissonian local fluctuations in momentum space, is present in all regimes. The quasicondensate regime is, however, characterized by the presence of negative correlations between different momenta, in contrast to the Bogolyubov theory for Bose condensates, predicting positive correlations between opposite momenta. Our data are in good agreement with ab initio calculations. PMID- 26894691 TI - Comparative Analysis and Identification of miRNAs and Their Target Genes Responsive to Salt Stress in Diploid and Tetraploid Paulownia fortunei Seedlings. AB - Salt stress is a global environmental problem that affects plant growth and development. Paulownia fortunei is an adaptable and fast-growing deciduous tree native to China that is environmentally and economically important. MicroRNAs (miRNAs) play important regulatory roles in growth, development, and stress responses in plants. MiRNAs that respond to biotic stresses have been identified; however, how miRNAs in P. fortunei respond to salt stress has not yet been reported. To identify salt-stress-responsive miRNAs and predict their target genes, four small RNA and four degradome libraries were constructed from NaCl treated and NaCl-free leaves of P. fortunei seedlings. The results indicated that salt stress had different physiological effects on diploid and tetraploid P. fortunei. We detected 53 conserved miRNAs belonging to 17 miRNA families and 134 novel miRNAs in P. fortunei. Comparing their expression levels in diploid and tetraploid P. fortunei, we found 10 conserved and 10 novel miRNAs that were significantly differentially expressed under salt treatment, among them eight were identified as miRNAs probably associated with higher salt tolerance in tetraploid P. fortunei than in diploid P. fortunei. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to predict the functions of the target genes of the conserved and novel miRNAs. The expressions of 10 differentially expressed miRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR). This is the first report on P. fortunei miRNAs and their target genes under salt stress. The results provided information at the physiological and molecular levels for further research into the response mechanisms of P. fortunei to salt stress. PMID- 26894694 TI - Towards Realistic Implementations of a Majorana Surface Code. AB - Surface codes have emerged as promising candidates for quantum information processing. Building on the previous idea to realize the physical qubits of such systems in terms of Majorana bound states supported by topological semiconductor nanowires, we show that the basic code operations, namely projective stabilizer measurements and qubit manipulations, can be implemented by conventional tunnel conductance probes and charge pumping via single-electron transistors, respectively. The simplicity of the access scheme suggests that a functional code might be in close experimental reach. PMID- 26894695 TI - Gravitational Waves from Isolated Systems: Surprising Consequences of a Positive Cosmological Constant. AB - There is a deep tension between the well-developed theory of gravitational waves from isolated systems and the presence of a positive cosmological constant Lambda, however tiny. In particular a generalization of Einstein's 1918 quadrupole formula that would allow a positive Lambda is not yet available. We first explain the principal difficulties and then show that it is possible to overcome them in the weak field limit. These results also provide concrete hints for constructing the Lambda>0 generalization of the Bondi-Sachs framework for full, nonlinear general relativity. PMID- 26894696 TI - Strong Support for the Millisecond Pulsar Origin of the Galactic Center GeV Excess. AB - Using gamma-ray data from the Fermi Large Area Telescope, various groups have identified a clear excess emission in the Inner Galaxy, at energies around a few GeV. This excess resembles remarkably well a signal from dark-matter annihilation. One of the most compelling astrophysical interpretations is that the excess is caused by the combined effect of a previously undetected population of dim gamma-ray sources. Because of their spectral similarity, the best candidates are millisecond pulsars. Here, we search for this hypothetical source population, using a novel approach based on wavelet decomposition of the gamma ray sky and the statistics of Gaussian random fields. Using almost seven years of Fermi-LAT data, we detect a clustering of photons as predicted for the hypothetical population of millisecond pulsar, with a statistical significance of 10.0sigma. For plausible values of the luminosity function, this population explains 100% of the observed excess emission. We argue that other extragalactic or Galactic sources, a mismodeling of Galactic diffuse emission, or the thick disk population of pulsars are unlikely to account for this observation. PMID- 26894697 TI - Evidence for Unresolved gamma-Ray Point Sources in the Inner Galaxy. AB - We present a new method to characterize unresolved point sources (PSs) generalizing traditional template fits to account for non-Poissonian photon statistics. We apply this method to Fermi Large Area Telescope gamma-ray data to characterize PS populations at high latitudes and in the Inner Galaxy. We find that PSs (resolved and unresolved) account for ~50% of the total extragalactic gamma-ray background in the energy range ~1.9 to 11.9 GeV. Within 10 degrees of the Galactic Center with |b|>=2 degrees , we find that ~5%-10% of the flux can be accounted for by a population of unresolved PSs distributed consistently with the observed ~GeV gamma-ray excess in this region. The excess is fully absorbed by such a population, in preference to dark-matter annihilation. The inferred source population is dominated by near-threshold sources, which may be detectable in future searches. PMID- 26894699 TI - Extracting Information about the Initial State from the Black Hole Radiation. AB - The crux of the black hole information paradox is related to the fact that the complete information about the initial state of a quantum field in a collapsing spacetime is not available to future asymptotic observers, belying the expectations from a unitary quantum theory. We study the imprints of the initial quantum state contained in a specific class of distortions of the black hole radiation and identify the classes of in states that can be partially or fully reconstructed from the information contained within. Even for the general in state, we can uncover some specific information. These results suggest that a classical collapse scenario ignores this richness of information in the resulting spectrum and a consistent quantum treatment of the entire collapse process might allow us to retrieve much more information from the spectrum of the final radiation. PMID- 26894698 TI - Approaching Free Fall on Two Degrees of Freedom: Simultaneous Measurement of Residual Force and Torque on a Double Torsion Pendulum. AB - A torsion pendulum with 2 soft degrees of freedom (DOFs), realized by off-axis cascading two torsion fibers, has been built and operated. This instrument helps characterize the geodesic motion of a test mass for LISA Pathfinder or any other free-fall space mission, providing information on cross talk and other effects that cannot be detected when monitoring a single DOF. We show that it is possible to simultaneously measure both the residual force and the residual torque acting on a quasifree test mass. As an example of the investigations that a double pendulum allows, we report the measurement of the force-to-torque cross talk, i.e., the amount of actuation signal, produced by applying a force on the suspended test mass, that leaks into the rotational DOF, detected by measuring the corresponding (unwanted) torque. PMID- 26894700 TI - Manifestly Local Theory of Vacuum Energy Sequestering. AB - We present a manifestly local, diffeomorphism invariant, and locally Poincare invariant formulation of vacuum energy sequestering. In this theory, quantum vacuum energy generated by matter loops is canceled by auxiliary fields. The auxiliary fields decouple from gravity almost completely. Their only residual effect is an a priori arbitrary, finite contribution to the curvature of the background geometry, which is radiatively stable. Its value is to be determined by a measurement, like the finite part of any radiatively stable UV-sensitive quantity in quantum field theory. PMID- 26894701 TI - Cosmologically Safe QCD Axion without Fine-Tuning. AB - Although QCD axion models are widely studied as solutions to the strong CP problem, they generically confront severe fine-tuning problems to guarantee the anomalous Peccei-Quinn (PQ) symmetry. In this Letter, we propose a simple QCD axion model without any fine-tunings. We introduce an extra dimension and a pair of extra quarks living on two branes separately, which is also charged under a bulk Abelian gauge symmetry. We assume a monopole condensation on our brane at an intermediate scale, which implies that the extra quarks develop chiral symmetry breaking and the PQ symmetry is broken. In contrast to Kim's original model, our model explains the origin of the PQ symmetry thanks to the extra dimension and avoids the cosmological domain wall problem because of chiral symmetry breaking in Abelian gauge theory. PMID- 26894704 TI - Top Quark Pair Production in Association with a Jet with Next-to-Leading-Order QCD Off-Shell Effects at the Large Hadron Collider. AB - We present a complete description of top quark pair production in association with a jet in the dilepton channel. Our calculation is accurate to next-to leading order (NLO) in QCD and includes all nonresonant diagrams, interferences, and off-shell effects of the top quark. Moreover, nonresonant and off-shell effects due to the finite W gauge boson width are taken into account. This calculation constitutes the first fully realistic NLO computation for top quark pair production with a final state jet in hadronic collisions. Numerical results for differential distributions as well as total cross sections are presented for the Large Hadron Collider at 8 TeV. With our inclusive cuts, NLO predictions reduce the unphysical scale dependence by more than a factor of 3 and lower the total rate by about 13% compared to leading-order QCD predictions. In addition, the size of the top quark off-shell effects is estimated to be below 2%. PMID- 26894706 TI - Collective and Single-Particle Motion in Beyond Mean Field Approaches. AB - We present a novel nuclear energy density functional method to calculate spectroscopic properties of atomic nuclei. Intrinsic nuclear quadrupole deformations and rotational frequencies are considered simultaneously as the degrees of freedom within a symmetry conserving configuration mixing framework. The present method allows the study of nuclear states with collective and single particle character. We calculate the fascinating structure of the semimagic ^{44}S nucleus as a first application of the method, obtaining an excellent quantitative agreement both with the available experimental data and with state of-the-art shell model calculations. PMID- 26894705 TI - Candidate Resonant Tetraneutron State Populated by the ^{4}He(^{8}He,^{8}Be) Reaction. AB - A candidate resonant tetraneutron state is found in the missing-mass spectrum obtained in the double-charge-exchange reaction ^{4}He(^{8}He,^{8}Be) at 186 MeV/u. The energy of the state is 0.83+/-0.65(stat)+/-1.25(syst) MeV above the threshold of four-neutron decay with a significance level of 4.9sigma. Utilizing the large positive Q value of the (^{8}He,^{8}Be) reaction, an almost recoilless condition of the four-neutron system was achieved so as to obtain a weakly interacting four-neutron system efficiently. PMID- 26894708 TI - Two-Dimensional Frequency Resolved Optomolecular Gating of High-Order Harmonic Generation. AB - Probing electronic wave functions of polyatomic molecules is one of the major challenges in high-harmonic spectroscopy. The extremely nonlinear nature of the laser-molecule interaction couples the multiple degrees of freedom of the probed system. We combine two-dimensional control of the electron trajectories and vibrational control of the molecules to disentangle the two main steps in high harmonic generation-ionization and recombination. We introduce a new measurement scheme, frequency-resolved optomolecular gating, which resolves the temporal amplitude and phase of the harmonic emission from excited molecules. Focusing on the study of vibrational motion in N_{2}O_{4}, we show that such advanced schemes provide a unique insight into the structural and dynamical properties of the underlying mechanism. PMID- 26894707 TI - Probing an Electron Scattering Resonance using Rydberg Molecules within a Dense and Ultracold Gas. AB - We present spectroscopy of a single Rydberg atom excited within a Bose-Einstein condensate. We not only observe the density shift as discovered by Amaldi and Segre in 1934, but a line shape that changes with the principal quantum number n. The line broadening depends precisely on the interaction potential energy curves of the Rydberg electron with the neutral atom perturbers. In particular, we show the relevance of the triplet p-wave shape resonance in the e^{-}-Rb(5S) scattering, which significantly modifies the interaction potential. With a peak density of 5.5*10^{14} cm^{-3}, and therefore an interparticle spacing of 1300 a_{0} within a Bose-Einstein condensate, the potential energy curves can be probed at these Rydberg ion-neutral atom separations. We present a simple microscopic model for the spectroscopic line shape by treating the atoms overlapped with the Rydberg orbit as zero-velocity, uncorrelated, pointlike particles, with binding energies associated with their ion-neutral separation, and good agreement is found. PMID- 26894709 TI - Theoretical Hyperfine Structure of the Molecular Hydrogen Ion at the 1 ppm Level. AB - We revisit the malpha^{6}(m/M) order corrections to the hyperfine splitting in the H_{2}^{+} ion and find a hitherto unrecognized second-order relativistic contribution associated with the vibrational motion of the nuclei. Inclusion of this correction term produces theoretical predictions which are in excellent agreement with experimental data [K. B. Jefferts, Phys. Rev. Lett. 23, 1476 (1969)], thereby concluding a nearly 50-year-long theoretical quest to explain the experimental results within their 1-ppm error. The agreement between the theory and experiment corroborates the proton structural properties as derived from the hyperfine structure of atomic hydrogen. Our work furthermore indicates that, for future improvements, a full three-body evaluation of the malpha^{6}(m/M) correction term will be mandatory. PMID- 26894710 TI - Observation of Atom-Wave Beats Using a Kerr Modulator for Atom Waves. AB - A phase modulation puts the atom in a coherent superposition of quantum states with different kinetic energies. We have detected the interference of such modulated waves at the output of our atom interferometer, and we have observed beats at the difference of the modulation frequencies and its harmonics, in good agreement with theory. The phase modulations were produced by a Kerr phase modulator, i.e., by the propagation of the atom wave in a time-dependent electric field. An extension of this technique to electron interferometry should open the way to very high temporal resolution in electron microscopy. PMID- 26894711 TI - Approaching the Heisenberg Limit without Single-Particle Detection. AB - We propose an approach to quantum phase estimation that can attain precision near the Heisenberg limit without requiring single-particle-resolved state detection. We show that the "one-axis twisting" interaction, well known for generating spin squeezing in atomic ensembles, can also amplify the output signal of an entanglement-enhanced interferometer to facilitate readout. Applying this interaction-based readout to oversqueezed, non-Gaussian states yields a Heisenberg scaling in phase sensitivity, which persists in the presence of detection noise as large as the quantum projection noise of an unentangled ensemble. Even in dissipative implementations-e.g., employing light-mediated interactions in an optical cavity or Rydberg dressing-the method significantly relaxes the detection resolution required for spectroscopy beyond the standard quantum limit. PMID- 26894702 TI - Measurements of Absolute Hadronic Branching Fractions of the Lambda_{c}^{+} Baryon. AB - We report the first measurement of absolute hadronic branching fractions of Lambda_{c}^{+} baryon at the Lambda_{c}^{+}Lambda[over -]_{c}^{-} production threshold, in the 30 years since the Lambda_{c}^{+} discovery. In total, 12 Cabibbo-favored Lambda_{c}^{+} hadronic decay modes are analyzed with a double tag technique, based on a sample of 567 pb^{-1} of e^{+}e^{-} collisions at sqrt[s]=4.599 GeV recorded with the BESIII detector. A global least-squares fitter is utilized to improve the measured precision. Among the measurements for twelve Lambda_{c}^{+} decay modes, the branching fraction for Lambda_{c}^{+} >pK^{-}pi^{+} is determined to be (5.84+/-0.27+/-0.23)%, where the first uncertainty is statistical and the second is systematic. In addition, the measurements of the branching fractions of the other 11 Cabibbo-favored hadronic decay modes are significantly improved. PMID- 26894712 TI - Tunable Polarons of Slow-Light Polaritons in a Two-Dimensional Bose-Einstein Condensate. AB - When an impurity interacts with a bath of phonons it forms a polaron. For increasing interaction strengths the mass of the polaron increases and it can become self-trapped. For impurity atoms inside an atomic Bose-Einstein condensate (BEC) the nature of this transition is not understood. While Feynman's variational approach to the Frohlich model predicts a sharp transition for light impurities, renormalization group studies always predict an extended intermediate coupling region characterized by large phonon correlations. To investigate this intricate regime and to test polaron physics beyond the validity of the Frohlich model we suggest a versatile experimental setup that allows us to tune both the mass of the impurity and its interactions with the BEC. The impurity is realized as a dark-state polariton (DSP) inside a quasi-two-dimensional BEC. We show that its interactions with the Bogoliubov phonons lead to photonic polarons, described by the Bogoliubov-Frohlich Hamiltonian, and make theoretical predictions using an extension of a recently introduced renormalization group approach to Frohlich polarons. PMID- 26894713 TI - Universal Scaling of Spectral Fluctuation Transitions for Interacting Chaotic Systems. AB - The statistical properties of interacting strongly chaotic systems are investigated for varying interaction strength. In order to model tunable entangling interactions between such systems, we introduce a new class of random matrix transition ensembles. The nearest-neighbor-spacing distribution shows a very sensitive transition from Poisson statistics to those of random matrix theory as the interaction increases. The transition is universal and depends on a single scaling parameter only. We derive the analytic relationship between the model parameters and those of a bipartite system, with explicit results for coupled kicked rotors, a dynamical systems paradigm for interacting chaotic systems. With this relationship the spectral fluctuations for both are in perfect agreement. An accurate approximation of the nearest-neighbor-spacing distribution as a function of the transition parameter is derived using perturbation theory. PMID- 26894714 TI - Nonlinear Generation of Vorticity by Surface Waves. AB - We demonstrate that waves excited on a fluid surface produce local surface rotation owing to hydrodynamic nonlinearity. We examine theoretically the effect and obtain an explicit formula for the vertical vorticity in terms of the surface elevation. Our theoretical predictions are confirmed by measurements of surface motion in a cell with water where surface waves are excited by vertical and harmonic shaking the cell. The experimental data are in good agreement with the theoretical predictions. We discuss physical consequences of the effect. PMID- 26894715 TI - Interaction of an Ultrarelativistic Electron Bunch Train with a W-Band Accelerating Structure: High Power and High Gradient. AB - Electron beam interaction with high frequency structures (beyond microwave regime) has a great impact on future high energy frontier machines. We report on the generation of multimegawatt pulsed rf power at 91 GHz in a planar metallic accelerating structure driven by an ultrarelativistic electron bunch train. This slow-wave wakefield device can also be used for high gradient acceleration of electrons with a stable rf phase and amplitude which are controlled by manipulation of the bunch train. To achieve precise control of the rf pulse properties, a two-beam wakefield interferometry method was developed in which the rf pulse, due to the interference of the wakefields from the two bunches, was measured as a function of bunch separation. Measurements of the energy change of a trailing electron bunch as a function of the bunch separation confirmed the interferometry method. PMID- 26894716 TI - Carbon Honeycomb High Capacity Storage for Gaseous and Liquid Species. AB - We report an exceptionally stable honeycomb carbon allotrope obtained by deposition of vacuum-sublimated graphite. The allotrope structures are derived from our low temperature electron diffraction and electron microscopy data. These structures can be both periodic and random and are built exclusively from sp^{2} bonded carbon atoms, and may be considered as three-dimensional graphene. They demonstrate high levels of physical absorption of various gases unattainable in other carbon forms such as fullerites or nanotubes. These honeycomb structures can be used not only for storage of various gases and liquids but also as a matrix for new composites. PMID- 26894717 TI - Critical Fragmentation Properties of Random Drilling: How Many Holes Need to Be Drilled to Collapse a Wooden Cube? AB - A solid wooden cube fragments into pieces as we sequentially drill holes through it randomly. This seemingly straightforward observation encompasses deep and nontrivial geometrical and probabilistic behavior that is discussed here. Combining numerical simulations and rigorous results, we find off-critical scale free behavior and a continuous transition at a critical density of holes that significantly differs from classical percolation. PMID- 26894718 TI - Phase Transition for Quenched Coupled Replicas in a Plaquette Spin Model of Glasses. AB - We study a three-dimensional plaquette spin model whose low temperature dynamics is glassy, due to localized defects and effective kinetic constraints. The thermodynamics of this system is smooth at all temperatures. We show that coupling it to a second system with a fixed (quenched) configuration leads to a phase transition, at finite coupling. The order parameter is the overlap between the copies, and the transition is between phases of low and high overlap. We find critical points whose properties are consistent with random-field Ising universality. We analyze the interfacial free energy cost between the high- and low-overlap states that coexist at (and below) the critical point, and we use this cost as the basis for a finite-size scaling analysis. We discuss these results in the context of mean-field and dynamical facilitation theories of the glass transition. PMID- 26894719 TI - Effects of Sublattice Symmetry and Frustration on Ionic Transport in Garnet Solid Electrolytes. AB - We use rigorous group-theoretic techniques and molecular dynamics to investigate the connection between structural symmetry and ionic conductivity in the garnet family of solid Li-ion electrolytes. We identify new ordered phases and order disorder phase transitions that are relevant for conductivity optimization. Ionic transport in this materials family is controlled by the frustration of the Li sublattice caused by incommensurability with the host structure at noninteger Li concentrations, while ordered phases explain regions of sharply lower conductivity. Disorder is therefore predicted to be optimal for ionic transport in this and other conductor families with strong Li interaction. PMID- 26894720 TI - Lateral Hopping of CO on Ag(110) by Multiple Overtone Excitation. AB - A novel type of action spectrum representing multiple overtone excitations of the v(M-C) mode was observed for lateral hopping of a CO molecule on Ag(110) induced by inelastically tunneled electrons from the tip of a scanning tunneling microscope. The yield of CO hopping shows sharp increases at 261+/-4 mV, corresponding to the C-O internal stretching mode, and at 61+/-2, 90+/-2, and 148+/-7 mV, even in the absence of corresponding fundamental vibrational modes. The mechanism of lateral CO hopping on Ag(110) was explained by the multistep excitation of overtone modes of v(M-C) based on the numerical fitting of the action spectra, the nonlinear dependence of the hopping rate on the tunneling current, and the hopping barrier obtained from thermal diffusion experiments. PMID- 26894721 TI - Curvature Dependence of the Liquid-Vapor Surface Tension beyond the Tolman Approximation. AB - Surface tension is a macroscopic manifestation of the cohesion of matter, and its value sigma_{infinity} is readily measured for a flat liquid-vapor interface. For interfaces with a small radius of curvature R, the surface tension might differ from sigma_{infinity}. The Tolman equation, sigma(R)=sigma_{infinity}/(1+2delta/R), with delta a constant length, is commonly used to describe nanoscale phenomena such as nucleation. Here we report experiments on nucleation of bubbles in ethanol and n-heptane, and their analysis in combination with their counterparts for the nucleation of droplets in supersaturated vapors, and with water data. We show that neither a constant surface tension nor the Tolman equation can consistently describe the data. We also investigate a model including 1/R and 1/R^{2} terms in sigma(R). We describe a general procedure to obtain the coefficients of these terms from detailed nucleation experiments. This work explains the conflicting values obtained for the Tolman length in previous analyses, and suggests directions for future work. PMID- 26894722 TI - Simple Screened Hydrogen Model of Excitons in Two-Dimensional Materials. AB - We present a generalized hydrogen model for the binding energies (E_{B}) and radii of excitons in two-dimensional (2D) materials that sheds light on the fundamental differences between excitons in two and three dimensions. In contrast to the well-known hydrogen model of three-dimensional (3D) excitons, the description of 2D excitons is complicated by the fact that the screening cannot be assumed to be local. We show that one can consistently define an effective 2D dielectric constant by averaging the screening over the extend of the exciton. For an ideal 2D semiconductor this leads to a simple expression for E_{B} that only depends on the excitonic mass and the 2D polarizability alpha. The model is shown to produce accurate results for 51 transition metal dichalcogenides. Remarkably, over a wide range of polarizabilities the binding energy becomes independent of the mass and we obtain E_{B}^{2D}~3/(4pialpha), which explains the recently observed linear scaling of exciton binding energies with band gap. It is also shown that the model accurately reproduces the nonhydrogenic Rydberg series in WS_{2} and can account for screening from the environment. PMID- 26894723 TI - Theory of Valence Transition in BiNiO_{3}. AB - Motivated by the colossal negative thermal expansion recently found in BiNiO_{3}, the valence transition accompanied by the charge transfer between the Bi and Ni sites is theoretically studied. We introduce an effective model for Bi-6s and Ni 3d orbitals taking into account the valence skipping of Bi cations, and investigate the ground-state and finite-temperature phase diagrams within the mean-field approximation. We find that the valence transition is caused by commensurate locking of the electron filling in each orbital associated with charge and magnetic orderings, and the critical temperature and the nature of the transitions are strongly affected by the relative energy between the Bi and Ni levels and the effective electron-electron interaction in the Bi sites. The obtained phase diagram well explains the temperature- and pressure-driven valence transitions in BiNiO_{3} and the systematic variation of valence states for a series of Bi and Pb perovskite oxides. PMID- 26894724 TI - Energy Gaps and Layer Polarization of Integer and Fractional Quantum Hall States in Bilayer Graphene. AB - Owing to the spin, valley, and orbital symmetries, the lowest Landau level in bilayer graphene exhibits multicomponent quantum Hall ferromagnetism. Using transport spectroscopy, we investigate the energy gaps of integer and fractional quantum Hall (QH) states in bilayer graphene with controlled layer polarization. The state at filling factor nu=1 has two distinct phases: a layer polarized state that has a larger energy gap and is stabilized by high electric field, and a hitherto unobserved interlayer coherent state with a smaller gap that is stabilized by large magnetic field. In contrast, the nu=2/3 quantum Hall state and a feature at nu=1/2 are only resolved at finite electric field and large magnetic field. These results underscore the importance of controlling layer polarization in understanding the competing symmetries in the unusual QH system of BLG. PMID- 26894725 TI - Effective Confining Potential of Quantum States in Disordered Media. AB - The amplitude of localized quantum states in random or disordered media may exhibit long-range exponential decay. We present here a theory that unveils the existence of an effective potential which finely governs the confinement of these states. In this picture, the boundaries of the localization subregions for low energy eigenfunctions correspond to the barriers of this effective potential, and the long-range exponential decay characteristic of Anderson localization is explained as the consequence of multiple tunneling in the dense network of barriers created by this effective potential. Finally, we show that Weyl's formula based on this potential turns out to be a remarkable approximation of the density of states for a large variety of one-dimensional systems, periodic or random. PMID- 26894726 TI - Mott Electrons in an Artificial Graphenelike Crystal of Rare-Earth Nickelate. AB - Deterministic control over the periodic geometrical arrangement of the constituent atoms is the backbone of the material properties, which, along with the interactions, define the electronic and magnetic ground state. Following this notion, a bilayer of a prototypical rare-earth nickelate, NdNiO_{3}, combined with a dielectric spacer, LaAlO_{3}, has been layered along the pseudocubic [111] direction. The resulting artificial graphenelike Mott crystal with magnetic 3d electrons has antiferromagnetic correlations. In addition, a combination of resonant X-ray linear dichroism measurements and ab initio calculations reveal the presence of an ordered orbital pattern, which is unattainable in either bulk nickelates or nickelate based heterostructures grown along the [001] direction. These findings highlight another promising venue towards designing new quantum many-body states by virtue of geometrical engineering. PMID- 26894727 TI - Orbital Selectivity in Scanning Tunneling Microscopy: Distance-Dependent Tunneling Process Observed in Iron Nitride. AB - In scanning tunneling microscopy, orbital selectivity of the tunneling process can make the topographic image dependent on a tip-surface distance. We have found reproducible dependence of the images on the distance for a monatomic layer of iron nitride formed on a Cu(001) surface. Observed atomic images systematically change between a regular dot array and a dimerized structure depending on the tip surface distance, which turns out to be the only relevant parameter in the image variation. An accompanied change in the weight of Fe-3d local density of states to a tunneling background was detected in dI/dV spectra. These have been attributed to a shift in surface orbitals detected by the tip from the d states to the s/p states with increasing the tip-surface distance, consistent with an orbital assignment from first-principles calculations. PMID- 26894728 TI - Nonequilibrium Second-Order Phase Transition in a Cooper-Pair Insulator. AB - In certain disordered superconductors, upon increasing the magnetic field, superconductivity terminates with a direct transition into an insulating phase. This phase is comprised of localized Cooper pairs and is termed a Cooper-pair insulator. The current-voltage characteristics measured in this insulating phase are highly nonlinear and, at low temperatures, exhibit abrupt current jumps. Increasing the temperature diminishes the jumps until the current-voltage characteristics become continuous. We show that a direct correspondence exists between our system and systems that undergo an equilibrium, second-order, phase transition. We illustrate this correspondence by comparing our results to the van der Waals equation of state for the liquid-gas mixture. We use the similarities to identify a critical point where an out of equilibrium second-order-like phase transition occurs in our system. Approaching the critical point, we find a power law behavior with critical exponents that characterizes the transition. PMID- 26894729 TI - Tellurium Hydrides at High Pressures: High-Temperature Superconductors. AB - Observation of high-temperature superconductivity in compressed sulfur hydrides has generated an irresistible wave of searches for new hydrogen-containing superconductors. We herein report the prediction of high-T_{c} superconductivity in tellurium hydrides stabilized at megabar pressures identified by first principles calculations in combination with a swarm structure search. Although tellurium is isoelectronic to sulfur or selenium, its heavier atomic mass and weaker electronegativity makes tellurium hydrides fundamentally distinct from sulfur or selenium hydrides in stoichiometries, structures, and chemical bondings. We identify three metallic stoichiometries of H_{4}Te, H_{5}Te_{2}, and HTe_{3}, which are not predicted or known stable structures for sulfur or selenium hydrides. The two hydrogen-rich H_{4}Te and H_{5}Te_{2} phases are primarily ionic and contain exotic quasimolecular H_{2} and linear H_{3} units, respectively. Their high-T_{c} (e.g., 104 K for H_{4}Te at 170 GPa) superconductivity originates from the strong electron-phonon couplings associated with intermediate-frequency H-derived wagging and bending modes, a superconducting mechanism which differs substantially with those in sulfur or selenium hydrides where the high-frequency H-stretching vibrations make considerable contributions. PMID- 26894730 TI - Hidden Fermionic Excitation Boosting High-Temperature Superconductivity in Cuprates. AB - The dynamics of a microscopic cuprate model, namely, the two-dimensional Hubbard model, is studied with a cluster extension of the dynamical mean-field theory. We find a nontrivial structure of the frequency-dependent self-energies, which describes an unprecedented interplay between the pseudogap and superconductivity. We show that these properties are well described by quasiparticles hybridizing with (hidden) fermionic excitations, emergent from the strong electronic correlations. The hidden fermion enhances superconductivity via a mechanism distinct from a conventional boson-mediated pairing, and originates the normal state pseudogap. Though the hidden fermion is elusive in experiments, it can solve many experimental puzzles. PMID- 26894731 TI - Rectifying the Optical-Field-Induced Current in Dielectrics: Petahertz Diode. AB - Investigating a theoretical model of the optical-field-induced current in dielectrics driven by strong few-cycle laser pulses, we propose an asymmetric conducting of the current by forming a heterojunction made of two distinct dielectrics with a low hole mass (m_{h}^{*}?m_{e}^{*}) and low electron mass (m_{e}^{*}?m_{h}^{*}), respectively. This proposition introduces the novel concept of a petahertz (10^{15} Hz) diode to rectify the current in the petahertz domain, which should be a key ingredient for the electric signal manipulation of future light-wave electronics. Further, we suggest the candidate dielectrics for the heterojunction. PMID- 26894732 TI - Real-Time Tracking of Singlet Exciton Diffusion in Organic Semiconductors. AB - Exciton diffusion in organic materials provides the operational basis for functioning of such devices as organic solar cells and light-emitting diodes. Here we track the exciton diffusion process in organic semiconductors in real time with a novel technique based on femtosecond photoinduced absorption spectroscopy. Using vacuum-deposited C_{70} layers as a model system, we demonstrate an extremely high diffusion coefficient of D~3.5*10^{-3} cm^{2}/s that originates from a surprisingly low energetic disorder of <5 meV. The experimental results are well described by the analytical model and supported by extensive Monte Carlo simulations. The proposed noninvasive time-of-flight technique is deemed as a powerful tool for further development of organic optoelectronic components, such as simple layered solar cells, light-emitting diodes, and electrically pumped lasers. PMID- 26894733 TI - Large Spin-Wave Bullet in a Ferrimagnetic Insulator Driven by the Spin Hall Effect. AB - Because of its transverse nature, spin Hall effects (SHE) provide the possibility to excite and detect spin currents and magnetization dynamics even in magnetic insulators. Magnetic insulators are outstanding materials for the investigation of nonlinear phenomena and for novel low power spintronics applications because of their extremely low Gilbert damping. Here, we report on the direct imaging of electrically driven spin-torque ferromagnetic resonance (ST-FMR) in the ferrimagnetic insulator Y_{3}Fe_{5}O_{12} based on the excitation and detection by SHEs. The driven spin dynamics in Y_{3}Fe_{5}O_{12} is directly imaged by spatially resolved microfocused Brillouin light scattering spectroscopy. Previously, ST-FMR experiments assumed a uniform precession across the sample, which is not valid in our measurements. A strong spin-wave localization in the center of the sample is observed indicating the formation of a nonlinear, self localized spin-wave "bullet". PMID- 26894734 TI - Electric Field Control of Jahn-Teller Distortions in Bulk Perovskites. AB - The Jahn-Teller distortion, by its very nature, is often at the heart of the various electronic properties displayed by perovskites and related materials. Despite the Jahn-Teller mode being nonpolar, we devise and demonstrate, in the present Letter, an electric field control of Jahn-Teller distortions in bulk perovskites. The electric field control is enabled through an anharmonic lattice mode coupling between the Jahn-Teller distortion and a polar mode. We confirm this coupling and quantify it through first-principles calculations. The coupling will always exist within the Pb2_{1}m space group, which is found to be the favored ground state for various perovskites under sufficient tensile epitaxial strain. Intriguingly, the calculations reveal that this mechanism is not only restricted to Jahn-Teller active systems, promising a general route to tune or induce novel electronic functionality in perovskites as a whole. PMID- 26894736 TI - Collective Behavior of Quorum-Sensing Run-and-Tumble Particles under Confinement. AB - We study a generic model for quorum-sensing bacteria in circular confinement. Every bacterium produces signaling molecules, the local concentration of which triggers a response when a certain threshold is reached. If this response lowers the motility, then an aggregation of bacteria occurs which differs fundamentally from standard motility-induced phase separation due to the long-ranged nature of the concentration of signal molecules. We analyze this phenomenon analytically and by numerical simulations employing two different protocols leading to stationary cluster and ring morphologies, respectively. PMID- 26894735 TI - Constraints on Fluctuations in Sparsely Characterized Biological Systems. AB - Biochemical processes are inherently stochastic, creating molecular fluctuations in otherwise identical cells. Such "noise" is widespread but has proven difficult to analyze because most systems are sparsely characterized at the single cell level and because nonlinear stochastic models are analytically intractable. Here, we exactly relate average abundances, lifetimes, step sizes, and covariances for any pair of components in complex stochastic reaction systems even when the dynamics of other components are left unspecified. Using basic mathematical inequalities, we then establish bounds for whole classes of systems. These bounds highlight fundamental trade-offs that show how efficient assembly processes must invariably exhibit large fluctuations in subunit levels and how eliminating fluctuations in one cellular component requires creating heterogeneity in another. PMID- 26894737 TI - Binary Mixtures of Particles with Different Diffusivities Demix. AB - The influence of size differences, shape, mass, and persistent motion on phase separation in binary mixtures has been intensively studied. Here we focus on the exclusive role of diffusivity differences in binary mixtures of equal-sized particles. We find an effective attraction between the less diffusive particles, which are essentially caged in the surrounding species with the higher diffusion constant. This effect leads to phase separation for systems above a critical size: A single close-packed cluster made up of the less diffusive species emerges. Experiments for testing our predictions are outlined. PMID- 26894738 TI - Resolving Dynamic Properties of Polymers through Coarse-Grained Computational Studies. AB - Coupled length and time scales determine the dynamic behavior of polymers and underlie their unique viscoelastic properties. To resolve the long-time dynamics it is imperative to determine which time and length scales must be correctly modeled. Here we probe the degree of coarse graining required to simultaneously retain significant atomistic details and access large length and time scales. The degree of coarse graining in turn sets the minimum length scale instrumental in defining polymer properties and dynamics. Using linear polyethylene as a model system, we probe how the coarse-graining scale affects the measured dynamics. Iterative Boltzmann inversion is used to derive coarse-grained potentials with 2 6 methylene groups per coarse-grained bead from a fully atomistic melt simulation. We show that atomistic detail is critical to capturing large-scale dynamics. Using these models we simulate polyethylene melts for times over 500 MUs to study the viscoelastic properties of well-entangled polymer melts. PMID- 26894739 TI - Effects of Inertia on the Steady-Shear Rheology of Disordered Solids. AB - We study the finite-shear-rate rheology of disordered solids by means of molecular dynamics simulations in two dimensions. By systematically varying the damping strength zeta in the low-temperature limit, we identify two well-defined flow regimes, separated by a thin (temperature-dependent) crossover region. In the overdamped regime, the athermal rheology is governed by the competition between elastic forces and viscous forces, whose ratio gives the Weissenberg number Wi?zetagamma[over ]; the macroscopic stress Sigma follows the frequently encountered Herschel-Bulkley law Sigma=Sigma_{0}+ksqrt[Wi], with yield stress Sigma_{0}>0. In the underdamped (inertial) regime, dramatic changes in the rheology are observed for low damping: the flow curve becomes nonmonotonic. This change is not caused by longer-lived correlations in the particle dynamics at lower damping; instead, for weak dissipation, the sample heats up considerably due to, and in proportion to, the driving. By thermostating more or less underdamped systems, we are able to link quantitatively the rheology to the kinetic temperature and the shear rate, rescaled with Einstein's vibration frequency. PMID- 26894740 TI - Comment on "Enhancement of Second-Order Nonlinear-Optical Signals by Optical Stimulation". PMID- 26894741 TI - Goodman and Tisdale Reply. PMID- 26894742 TI - Erratum: Towards a Unified Description of the Rheology of Hard-Particle Suspensions [Phys. Rev. Lett. 115, 088304 (2015)]. AB - This corrects the article DOI: 10.1103/PhysRevLett.115.088304. PMID- 26894744 TI - Midwives' knowledge and attitudes when encountering Gender-Based Violence in their practice at a maternity-hospital in Kingston, Jamaica. AB - INTRODUCTION: Gender-based violence (GBV) can have devastating consequences for pregnancy because both mother and child are at risk. Midwives are in a strategic position to identify and empower pregnant women experiencing GBV; however, currently midwives in Jamaica are not required to screen for GBV, neither are they prepared to do so. AIM: This study forms the baseline of a larger study designed to improve the capacity of midwives to identify and treat pregnant women experiencing GBV in Jamaica. This specific component assessed midwives' knowledge and attitudes when encountering GBV in their practice in Kingston, Jamaica. METHODS: A qualitative study design was used. Six practicing midwives were purposely selected to participate in a focus group discussion at the antenatal clinic of a hospital in Kingston, Jamaica. RESULTS: All six respondents said it was very important to screen for GBV among pregnant women in their care. The findings from their report revolved around six themes, namely midwives have suboptimal knowledge, are exposed to women experiencing GBV in pregnancy, lack professional preparedness, report gaps in the institutional framework to guide their practice, are concerned for their safety and security, and are willing to intervene. CONCLUSION: This study confirmed that midwives are aware of the problem and are willing to intervene but are faced with lack of formal procedures to detect and treat pregnant women who are experiencing GBV. Findings could be used to inform a protocol which is being developed to guide midwives' practice. Findings could also be incorporated in the national strategy to eliminate GBV. PMID- 26894743 TI - Effects of GHRP-2 and Cysteamine Administration on Growth Performance, Somatotropic Axis Hormone and Muscle Protein Deposition in Yaks (Bos grunniens) with Growth Retardation. AB - The objective of this study was to investigate the effects of growth hormone releasing peptide-2 (GHRP-2) and cysteamine (CS) administration on growth performance in yaks with growth retardation and try to elucidate its regulatory mechanisms. Trial 1, thirty-six 1-year-old Qinghai high plateau yaks (body weight 38-83.2 kg) were randomly chosen for body weight and jugular blood samples collection. The relationship between body weight and serum GHRH (P < 0.05, R = 0.45), GH (P < 0.05, R = 0.47), IGF-1 (P < 0.05, R = 0.62) was significantly correlated in yaks colonies with lighter body weights. Trial 2, fifteen 1-year old Qinghai high plateau yaks with growth retardation (average body weight 54.8 +/- 8.24 kg) were randomly selected and assigned to negative control group (NG), GHRP-2 injection group (GG) and cysteamine feeding group (CG), with 5 yaks per group. Another five 1-year-old Qinghai high plateau yaks with normal growth performance (average body weight 75.3 +/- 2.43 kg) were selected as positive control group (PG). The average daily gain (ADG) of the GG and CG were significantly higher than those in the PG and NG (P < 0.05). Both GHRP-2 and CS administration significantly enhanced the myofiber diameter and area of skeletal muscle (P<0.05). GHRP-2 significantly enhanced the serum GH and IGF-1 levels (P < 0.05), and up-regulated GHR, IGF-1 and IGF-1R mRNA expression in the liver and skeletal muscle (P < 0.05), enhanced the mRNA expression of PI3K, AKt and mTOR in the skeletal muscle (P<0.05). CS significantly reduced the serum SS levels and the hypothalamus SS mRNA expression (P < 0.05), and enhanced GHR and IGF-1 mRNA expression in the liver (P < 0.05), decreased the mRNA expression of muscle atrophy F-box (Atrogin-1) and muscle ring finger 1 (MuRF1) mRNA (P < 0.05). CONCLUSIONS: Growth retardation in yaks was primarily due to somatotropic axis hormones secretion deficiency. Both GHRP-2 and CS administration can accelerate growth performance and GH, IGF-1 secretion in yaks with growth retardation. GHRP 2 enhanced muscle protein deposition mainly by up-regulated the protein synthesis pathways, whereas CS worked mainly by down-regulated the ubiquitin-proteasome pathway. PMID- 26894745 TI - Controlling Allosteric Networks in Proteins. AB - Allosteric transition, defined as conformational changes induced by ligand binding, is one of the fundamental properties of proteins. Allostery has been observed and characterized in many proteins, and has been recently utilized to control protein function via regulation of protein activity. Here, we review the physical and evolutionary origin of protein allostery, as well as its importance to protein regulation, drug discovery, and biological processes in living systems. We describe recently developed approaches to identify allosteric pathways, connected sets of pairwise interactions that are responsible for propagation of conformational change from the ligand-binding site to a distal functional site. We then present experimental and computational protein engineering approaches for control of protein function by modulation of allosteric sites. As an example of application of these approaches, we describe a synergistic computational and experimental approach to rescue the cystic-fibrosis associated protein cystic fibrosis transmembrane conductance regulator, which upon deletion of a single residue misfolds and causes disease. This example demonstrates the power of allosteric manipulation in proteins to both elucidate mechanisms of molecular function and to develop therapeutic strategies that rescue those functions. Allosteric control of proteins provides a tool to shine a light on the complex cascades of cellular processes and facilitate unprecedented interrogation of biological systems. PMID- 26894746 TI - Correction: Sampling and Complementarity Effects of Plant Diversity on Resource Use Increases the Invasion Resistance of Communities. PMID- 26894747 TI - Site-Specific Quantification of Surface N-Glycoproteins in Statin-Treated Liver Cells. AB - The frequent modification of cell-surface proteins by N-linked glycans is known to be correlated with many biological processes. Aberrant glycosylation on surface proteins is associated with different cellular statuses and disease progression. However, it is extraordinarily challenging to comprehensively and site-specifically analyze glycoproteins located only on the cell surface. Currently mass spectrometry (MS)-based proteomics provides the possibility to analyze the N-glycoproteome, but effective separation and enrichment methods are required for the analysis of surface glycoproteins prior to MS measurement. The introduction of bio-orthogonal groups into proteins accelerates research in the robust visualization, identification, and quantification of proteins. Here we have comprehensively evaluated different sugar analogs in the analysis of cell surface N-glycoproteins by combining copper-free click chemistry and MS-based proteomics. Comparison of three sugar analogs, N-azidoacetylgalactosamine (GalNAz), N-azidoacetylglucosamine (GlcNAz), and N-azidoacetylmannosamine (ManNAz), showed that metabolic labeling with GalNAz resulted in the greatest number of glycoproteins and glycosylation sites in biological duplicate experiments. GalNAz was then employed for the quantification experiment in statin treated HepG2 liver cells, and 280 unique N-glycosylated sites were quantified from 168 surface proteins. The quantification results demonstrated that many glycosylation sites on surface proteins were down-regulated in statin-treated cells compared to untreated cells because statin prevents the synthesis of dolichol, which is essential for the formation of dolichol-linked precursor oligosaccharides. Several glycosylation sites in proteins that participate in the Alzheimer's disease pathway were down-regulated. This method can be extensively applied for the global analysis of the cell-surface N-glycoproteome. PMID- 26894749 TI - Mesenchymal Stromal Cell-Derived Extracellular Vesicles Protect Against Acute Kidney Injury Through Anti-Oxidation by Enhancing Nrf2/ARE Activation in Rats. AB - BACKGROUND/AIMS: Anti-oxidation is an effective strategy for curing acute kidney injury (AKI). Herein, we suggest that extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) might play an anti-oxidative role by enhancing Nrf2/ARE activation in AKI. METHODS: EVs isolated from the conditioned medium of human Wharton's Jelly mesenchymal stromal cells and human foreskin fibroblast were intravenously injected in rats immediately after 45 min of unilateral kidney ischemia. Animals were sacrificed 24 h after injury. RESULTS: Results showed that renal tubular injury was alleviated and renal function was improved by MSC-EVs. Cell apoptosis and sNGAL levels, which reflect kidney cell injury, were reduced. Moreover, MSC-EVs decreased oxidative stress in injured kidney tissues and NRK 52E cells under hypoxia injury. Nrf2/antioxidant response element (ARE) enhancement and HO-1 up-regulation were further observed after MSC-EV treatment both in vivo and in vitro. CONCLUSIONS: MSC-EVs may protect against AKI possibly through anti-oxidation by enhancing Nrf2/ARE activation. PMID- 26894748 TI - Inferring Neuronal Dynamics from Calcium Imaging Data Using Biophysical Models and Bayesian Inference. AB - Calcium imaging has been used as a promising technique to monitor the dynamic activity of neuronal populations. However, the calcium trace is temporally smeared which restricts the extraction of quantities of interest such as spike trains of individual neurons. To address this issue, spike reconstruction algorithms have been introduced. One limitation of such reconstructions is that the underlying models are not informed about the biophysics of spike and burst generations. Such existing prior knowledge might be useful for constraining the possible solutions of spikes. Here we describe, in a novel Bayesian approach, how principled knowledge about neuronal dynamics can be employed to infer biophysical variables and parameters from fluorescence traces. By using both synthetic and in vitro recorded fluorescence traces, we demonstrate that the new approach is able to reconstruct different repetitive spiking and/or bursting patterns with accurate single spike resolution. Furthermore, we show that the high inference precision of the new approach is preserved even if the fluorescence trace is rather noisy or if the fluorescence transients show slow rise kinetics lasting several hundred milliseconds, and inhomogeneous rise and decay times. In addition, we discuss the use of the new approach for inferring parameter changes, e.g. due to a pharmacological intervention, as well as for inferring complex characteristics of immature neuronal circuits. PMID- 26894750 TI - Capturing Psychologists' Work in Academic Health Settings: The Role of the Educational Value Unit (EVU). AB - This paper describes how psychology faculty positions in academic health centers (AHCs) have evolved to meet the changing needs in healthcare. In that context, the roles of psychologists have expanded significantly to include a wide array of clinical responsibilities, teaching and supervisory roles, administrative functions, research initiatives, and academic scholarship. Traditionally, faculty compensation plans have been calculated through the use of Relative Value Units which are primarily based on clinical service delivery, hence, incomplete when attempting to account for these growing academic responsibilities. This paper reviews the need to expand the ways in which the work provided by psychologists is appropriately identified and compensated for in AHCs. Drawing upon six models utilized in other areas of medical education, this paper describes the potential utility of incorporating Educational Value Units as a metric for capturing this expanding set of academic responsibilities and systematically incorporating them into a psychologist's job design. Recommendations for future considerations are provided. PMID- 26894751 TI - Decompression of the gluteus medius muscle as a new treatment for buttock pain: technical note. AB - PURPOSE: The clinical features and etiology of low back pain and buttock pain remain poorly understood. We report ten patients with buttock pain who underwent gluteus medius muscle (GMeM) decompression under local anesthesia. METHODS: Between December 2012 and November 2013 we surgically treated ten patients (four men, six women; mean age 65.1 years) for buttock pain. The affected side was unilateral in seven and bilateral in three patients (total sites, n = 13). The interval from symptom onset to treatment averaged 174 months; the mean postoperative follow-up period was 24 months. Decompression of the tight gluteal aponeurosis over the GMeM was performed under local anesthesia. Assessment of the clinical outcomes was on the numeric rating scale (NRS) for low back pain (LBP), the Japanese Orthopedic Association (JOA) score, and the Roland-Morris Disability Questionnaire (RDQ) score before and at the latest follow-up after treatment. RESULTS: There were no intraoperative surgery-related complications. The buttock pain of all patients was improved after surgery; their NRS decreased from 7.0 to 0.8 and JOA and RMDQ scores indicated significant improvement (p < 0.05). CONCLUSION: In patients with buttock pain, pain around the GMeM should be considered as a causative factor. Less invasive surgery with cutting and opening of the tight gluteal aponeurosis over the GMeM under local anesthesia yielded excellent clinical outcomes. PMID- 26894752 TI - An Improved Ultrasensitive Enzyme-Linked Immunosorbent Assay Using Hydrangea-Like Antibody-Enzyme-Inorganic Three-in-One Nanocomposites. AB - Protein-inorganic nanoflowers, composed of protein and copper(II) phosphate (Cu3(PO4)2), have recently grabbed people's attention. Because the synthetic method requires no organic solvent and because of the distinct hierarchical nanostructure, protein-inorganic nanoflowers display enhanced catalytic activity and stability and would be a promising tool in biocatalytical processes and biological and biomedical fields. In this work, we first coimmobilized the enzyme, antibody, and Cu3(PO4)2 into a three-in-one hybrid protein-inorganic nanoflower to enable it to possess dual functions: (1) the antibody portion retains the ability to specifically capture the corresponding antigen; (2) the nanoflower has enhanced enzymatic activity and stability to produce an amplified signal. The prepared antibody-enzyme-inorganic nanoflower was first applied in an enzyme-linked immunosorbent assay to serve as a novel enzyme-labeled antibody for Escherichia coli O157:H7 (E. coli O157:H7) determination. The detection limit is 60 CFU L(-1), which is far superior to commercial ELISA systems. The three-in-one antibody (anti-E. coli O157:H7 antibody)-enzyme (horseradish peroxidase) inorganic (Cu3(PO4)2) nanoflower has some advantages over commercial enzyme antibody conjugates. First, it is much easier to prepare and does not need any complex covalent modification. Second, it has fairly high capture capability and catalytic activity because it is presented as aggregates of abundant antibodies and enzymes. Third, it has enhanced enzymatic stability compared to the free form of enzyme due to the unique hierarchical nanostructure. PMID- 26894754 TI - Role of Histamine Release Test for the Evaluation of Patients with Immediate Hypersensitivity Reactions to Clavulanic Acid. AB - BACKGROUND: Immediate hypersensitivity reactions to clavulanic acid (CLV) seem to be on the increase. Diagnosis is mainly based on skin testing and the drug provocation test (DPT), procedures that are not risk free. The aim of this study was to evaluate whether the histamine release test (HRT) could help evaluate patients with selective hypersensitivity to CLV. METHODS: Eighteen patients with immediate selective hypersensitivity reactions to CLV (positive skin tests to CLV but negative to the major and minor determinants of benzylpenicillin and amoxicillin; negative DPT to benzylpenicillin and amoxicillin) and 21 controls with tolerance to CLV were included. Direct and passive HRT, using patient whole blood or 'IgE-stripped' donor blood sensitized by patient serum, respectively, were performed by stimulating the blood with CLV, and basophil histamine release was detected by fluorometric determination. RESULTS: The clinical symptoms were anaphylaxis (n = 6), urticaria (n = 9) and urticaria-angioedema (n = 3). The median time interval between the reaction and the study was 225 days (interquartile range, IQR: 120-387.5) and between drug intake and the development of symptoms 30 min (IQR: 6.25-30). We obtained similar data for both the direct and passive HRT, with a sensitivity and specificity of 55 and 85%, respectively, a positive predictive value of 76% and a negative predictive value of 69%. CONCLUSIONS: The sensitivity of both the direct and passive HRT for diagnosing patients with immediate allergy to CLV is less than 60%. However, the passive HRT has the advantage that it is based on the testing of serum samples that can be handled more easily than fresh blood samples. PMID- 26894753 TI - The Utility of Molecular Imaging in Prostate Cancer. AB - Prostate cancer is the commonest solid-organ cancer diagnosed in males and represents an important source of morbidity and mortality worldwide. Imaging plays a crucial role in diagnosing prostate cancer and informs the ongoing management of the disease at all stages. Several novel molecular imaging technologies have been developed recently that have the potential to revolutionise disease diagnosis and the surveillance of patients living with prostate cancer. These innovations include hyperpolarised MRI, choline PET/CT and PSMA PET/CT. The major utility of choline and PSMA PET/CT currently lies in their sensitivity for detecting early recurrence after radical treatment for prostate cancer and identifying discrete lesions that may be amenable to salvage therapy. Molecular imaging is likely to play a future role in characterising genetic and biochemical signatures in individual tumours, which may be of particular significance as cancer therapies move into an era of precision medicine. PMID- 26894755 TI - Diabetes Pharmacotherapies and Bladder Cancer: A Medicare Epidemiologic Study. AB - OBJECTIVE: Patients with type II diabetes have an increased risk of bladder cancer and are commonly treated with thiazolidinediones and angiotensin receptor blockers (ARBs), which have been linked to cancer risk. We explored the relationship between use of one or both of these medication types and incident bladder cancer among diabetic patients (diabetics) enrolled in Medicare. RESEARCH DESIGN AND METHODS: We constructed both a prevalent and incident retrospective cohort of pharmacologically treated prevalent diabetics enrolled in a Medicare fee-for-service plan using inpatient, outpatient (2003-2011) and prescription (2006-2011) administrative data. The association of incident bladder cancer with exposure to pioglitazone, rosiglitazone and ARBs was studied using muitivariable Cox's hazard models with time-dependent covariates in each of the two cohorts. RESULTS: We identified 1,161,443 prevalent and 320,090 incident pharmacologically treated diabetics, among whom 4433 and 1159, respectively, developed incident bladder cancers. In the prevalent cohort mean age was 75.1 years, mean follow-up time was 38.0 months, 20.2% filled a prescription for pioglitazone during follow up, 10.4% received rosiglitazone, 31.6% received an ARB and 8.0% received combined therapy with pioglitazone + ARB. We found a positive association between bladder cancer and duration of pioglitazone use in the prevalent cohort (P for trend = 0.008), with >=24 months of pioglitazone exposure corresponding to a 16% (95% confidence interval 0-35%) increase in the incidence of bladder cancer compared to no use. There was a positive association between bladder cancer and rosiglitazone use for <24 months in the prevalent cohort, but no association with ARB use. There were no significant associations in the incident cohort. CONCLUSIONS: We found that the incidence of bladder cancer increased with duration of pioglitazone use in a prevalent cohort of diabetics aged 65+ years residing in the USA, but not an incident cohort. PMID- 26894756 TI - AM and DSE colonization of invasive plants in urban habitat: a study of Upper Silesia (southern Poland). AB - Interactions between invasive plants and root endophytes may contribute to the exploration of plant invasion causes. Twenty plant species of alien origin differing in invasiveness were studied in terms of status and typical structures of arbuscular mycorrhizal fungi and dark septate endophytes (DSE) in urban habitats in Silesia Upland (southern Poland). We observed that 75 % of investigated plant species were mycorrhizal. The arbuscular mycorrhiza (AM) of most plant species was of the Arum morphology. The nearly 100 % mycorrhizal frequency, high intensity of AM colonization within root cortex and the presence of arbuscules in all mycorrhizal plant species indicate that the investigated species are able to establish AM associations in the secondary range and urban habitats. DSE were present in all mycorrhizal and non-mycorrhizal species. The frequency of DSE was significantly lower in non-mycorrhizal group of plants, however, sclerotia of DSE were found mainly in the roots of non-mycorrhizal plant species. The group of species native to North America including three Solidago congeners have the highest values of all AM mycorrhization and DSE indices. Moreover, we observed that most mycorrhizal invasive species belonged to the family Asteraceae. In turn, representatives of Poaceae had the lowest values of AM mycorrhization. Nevertheless, quite high values of DSE frequency were also encountered in roots of Poaceae species. The high invasiveness of the representatives of the Asteraceae family from North America support theory that both taxonomic pattern, and the fact of root endophytes colonization contribute to invasion success. While, the taxa of Reynoutria also represent successful invaders but they are of Asiatic origin, non-mycorrhizal and weakly colonized by DSE fungi. PMID- 26894757 TI - Label-free molecular beacon for real-time monitoring of DNA polymerase activity. AB - Traditional methods for assaying DNA polymerase activity are discontinuous, time consuming, and laborious. Here, we report a new approach for label-free and real time monitoring of DNA polymerase activity using a Thioflavin T (ThT) probe. In the presence of DNA polymerase, the DNA primer could be elongated through polymerase reaction to open MB1, leading to the release of the G-quartets. These then bind to ThT to form ThT/G-quadruplexes with an obvious fluorescence generation. It exhibits a satisfying detection result for the activity of DNA polymerase with a low detection limit of 0.05 unit/ml. In addition, no labeling with a fluorophore or a fluorophore-quencher pair is required; this method is fairly simple, fast, and low cost. Furthermore, the proposed method was also applied to assay the inhibition of DNA polymerase activity. This approach may offer potential applications in drug screening, clinical diagnostics, and some other related biomedical research. PMID- 26894758 TI - Evaluation of synergistic enantioseparation systems with chiral spirocyclic ionic liquids as additives by capillary electrophoresis. AB - In recent years, chiral ionic liquids (CILs) have attracted more and more attention in the field of enantioseparation. In this study, two novel spirocyclic chiral ionic liquids, 1-butyl-3-methylimidazolium(T-4)-bis[(2S)-2-(hydroxy kappaO)-3-methylbutanoato-kappaO]borate (BMIm(+)BLHvB(-)) and 1-butyl-3 methylimidazolium (T-4)-bis[(alphaS)-alpha-(hydroxy-kappaO)-4 methylbenzeneacetato-kappaO]borate (BMIm(+)BSMB(-)), were applied for the first time in capillary electrophoresis (CE) to establish synergistic systems for enantiomeric separation. Significantly improved separations of five tested analytes were observed in the CILs synergistic systems based on three beta cyclodextrin derivatives (CD), compared with conventional single CD separation systems. Several principal parameters such as CILs concentration, cyclodextrin concentration, buffer pH, and applied voltage were systematically investigated with BMIm(+)BLHvB(-)/hydroxypropyl-beta-CD selected as a model system to optimize the enantioseparation. Molecular modeling was applied to further demonstrate the chiral recognition mechanism of the CILs/hydroxypropyl-beta-CD synergistic system, which showed a good agreement with the experimental results. PMID- 26894759 TI - Impact of and correction for instrument sensitivity drift on nanoparticle size measurements by single-particle ICP-MS. AB - The effect of ICP-MS instrument sensitivity drift on the accuracy of nanoparticle (NP) size measurements using single particle (sp)ICP-MS is investigated. Theoretical modeling and experimental measurements of the impact of instrument sensitivity drift are in agreement and indicate that drift can impact the measured size of spherical NPs by up to 25 %. Given this substantial bias in the measured size, a method was developed using an internal standard to correct for the impact of drift and was shown to accurately correct for a decrease in instrument sensitivity of up to 50 % for 30 and 60 nm gold nanoparticles. Graphical Abstract Correction of nanoparticle size measurement by spICP-MS using an internal standard. PMID- 26894760 TI - Comprehensive peptide marker identification for the detection of multiple nut allergens using a non-targeted LC-HRMS multi-method. AB - Food allergies have emerged as a global problem over the last few decades; therefore, reliable and sensitive analytical methods to ensure food safety for allergic consumers are required. The application of mass spectrometry is of growing interest in this field and several procedures based on low resolution tandem mass spectrometry using single tryptic peptides as analytical targets have recently been described. However, a comprehensive survey of marker peptides for the development of multi-methods is still missing, as is a consensus guide to marker identification. In this study, we therefore report a consistent approach to the development of liquid chromatography-mass spectrometry (LC-MS) multi screening methods for the detection of allergens in food matrices. Proteotypic peptides were identified by a shotgun proteomics approach and verified through a thorough investigation of specificity and sensitivity. On the basis of this procedure, we identified 44 suitable tryptic marker peptides from six allergenic nut species and developed the first analytical LC-MS method for the detection of trace nut contaminations in processed foods using high resolution mass spectrometry (HRMS). The analysis of spiked matrix samples gave limits of detection (LODs) below 10 MUg/g for several nuts; these LODs are comparable with routinely used methods such as ELISA and PCR. Notably, the HRMS approach can be used in an untargeted fashion to identify multiple allergens also retrospectively. In conclusion, we present here the so far largest consensus set of analytical markers from nut allergens and to the best of our knowledge the first multi-allergen method based on LC-HRMS. PMID- 26894761 TI - Erratum to: FragClust and TestClust, two informatics tools for chemical structure hierarchical clustering analysis applied to lipidomics. The example of Alzheimer's disease. PMID- 26894762 TI - Collection and separation of extract in dispersive liquid-liquid microextraction with hollow fiber. AB - Dispersive liquid-liquid microextraction combined with collection of the extraction phase with the hollow fiber was applied to the extraction of estrogens from environmental water samples. 1-Undecanol with relatively lower toxicity was used as the extraction solvent. The hollow fiber was used to collect the extraction phase containing the analytes from the aqueous phase. Hollow fibers collecting the extraction phase were eluted with acetonitrile and the resulting eluate was analyzed by high performance liquid chromatography. Several parameters, including pH of sample, the type and volume of the extraction and dispersive solvent, salt concentration, extraction time, and collection time were optimized. Under the optimal experimental conditions, the limits of detection for estriol, 17alpha-estradiol, and ethynylestradiol were 4.58, 1.41, and 1.41 MUg L( 1), respectively. When the present method was applied to the analysis of real water samples, the recoveries of estrogens at two spiked levels were in the range of 55.8-107.4%. In this method, the separation of the extraction phase and aqueous phase becomes easy with no need for centrifugation, refrigeration-thaw, or any special device. The hollow fiber was commercially available and the collection procedure was easy to perform, which make the present method have potential for automation and wide promotion. Small sizes of pores on the walls of the hollow fibers can block large molecules, which makes the present method have the potential for the treatment of complex matrices. PMID- 26894763 TI - Removal of Polysorbate 80 by complexation prior to LC-MS analysis. AB - The presence of Polysorbate 80 in samples can challenge liquid chromatography electrospray ionisation mass spectrometry (LC-ESI-MS) analysis as it is easily ionised and detected. In this study, we demonstrate that interference from Polysorbate 80 can be reduced by complexation with a metal ion followed by precipitation by thiocyanate. The precipitation procedure was tested on a mixture of low molecular weight compounds (e.g. amino acids and non-amino organic acids) and it was shown that none of the tested compounds were precipitated. PMID- 26894764 TI - Plasmodium falciparum Hsp70-z, an Hsp110 homologue, exhibits independent chaperone activity and interacts with Hsp70-1 in a nucleotide-dependent fashion. AB - The role of molecular chaperones, among them heat shock proteins (Hsps), in the development of malaria parasites has been well documented. Hsp70s are molecular chaperones that facilitate protein folding. Hsp70 proteins are composed of an N terminal nucleotide binding domain (NBD), which confers them with ATPase activity and a C-terminal substrate binding domain (SBD). In the ADP-bound state, Hsp70 possesses high affinity for substrate and releases the folded substrate when it is bound to ATP. The two domains are connected by a conserved linker segment. Hsp110 proteins possess an extended lid segment, a feature that distinguishes them from canonical Hsp70s. Plasmodium falciparum Hsp70-z (PfHsp70-z) is a member of the Hsp110 family of Hsp70-like proteins. PfHsp70-z is essential for survival of malaria parasites and is thought to play an important role as a molecular chaperone and nucleotide exchange factor of its cytosolic canonical Hsp70 counterpart, PfHsp70-1. Unlike PfHsp70-1 whose functions are fairly well established, the structure-function features of PfHsp70-z remain to be fully elucidated. In the current study, we established that PfHsp70-z possesses independent chaperone activity. In fact, PfHsp70-z appears to be marginally more effective in suppressing protein aggregation than its cytosol-localized partner, PfHsp70-1. Furthermore, based on coimmunoaffinity chromatography and surface plasmon resonance analyses, PfHsp70-z associated with PfHsp70-1 in a nucleotide dependent fashion. Our findings suggest that besides serving as a molecular chaperone, PfHsp70-z could facilitate the nucleotide exchange function of PfHsp70 1. These dual functions explain why it is essential for parasite survival. PMID- 26894766 TI - The Influence of the pi-Conjugated Spacer on Photophysical Properties of Difluoroboranyls Derived from Amides Carrying a Donor Group. AB - A series of difluoroboranyls derived from amides carrying a variable pi conjugated spacer between the electron-donating (D) and electron-accepting (A) groups was synthesized and characterized with (1)H, (11)B, (13)C, (15)N, and (19)F NMR, electronic absorption, fluorescence spectroscopies, and first principle calculations. The D-to-A distance in the series varied from 1.5 to 4.5 A, causing bathochromic shifts of both the absorption and fluorescence maxima by more than 120 and 213 nm, respectively. These trends are rationalized by quantum mechanical calculations that allow for quantification of the charge-transfer distance. Theoretical calculations were also performed to determine the vibronic couplings and thus to reproduce the experimental band shapes. PMID- 26894765 TI - Determinants of rodent longevity in the chaperone-protein degradation network. AB - Proteostasis is an integral component of healthy aging, ensuring maintenance of protein structural and functional integrity with concomitant impact upon health span and longevity. In most metazoans, increasing age is accompanied by a decline in protein quality control resulting in the accrual of damaged, self-aggregating cytotoxic proteins. A notable exception to this trend is observed in the longest lived rodent, the naked mole-rat (NMR, Heterocephalus glaber) which maintains proteostasis and proteasome-mediated degradation and autophagy during aging. We hypothesized that high levels of the proteolytic degradation may enable better maintenance of proteostasis during aging contributing to enhanced species maximum lifespan potential (MLSP). We test this by examining proteasome activity, proteasome-related HSPs, the heat-shock factor 1 (HSF1) transcription factor, and several markers of autophagy in the liver and quadriceps muscles of eight rodent species with divergent MLSP. All subterranean-dwelling species had higher levels of proteasome activity and autophagy, possibly linked to having to dig in soils rich in heavy metals and where underground atmospheres have reduced oxygen availability. Even after correcting for phylogenetic relatedness, a significant (p < 0.02) positive correlation between MLSP, HSP25, HSF1, proteasome activity, and autophagy-related protein 12 (ATG12) was observed, suggesting that the proteolytic degradation machinery and maintenance of protein quality play a pivotal role in species longevity among rodents. PMID- 26894768 TI - Unusual Histopathological Patterns in Melanocytic Nevi With Some Previously Undescribed Patterns. AB - Melanocytic nevi are one of the most common diagnoses in the daily practice of any dermatopathologist. Although in the vast majority of cases the final diagnosis is not difficult, there are certain rare and unusual morphologic variations that can elicit some diagnostic problems. Although some of these variations can be considered as mere morphologic oddities, others might lead to a differential diagnosis with melanoma, or with other tumors, including epithelial or neural tumors. In the current report, we review many of these morphologic variations and discuss the main differential diagnosis, when appropriate. PMID- 26894767 TI - Percutaneous Lumbopelvic Fixation for Reduction and Stabilization of Sacral Fractures With Spinopelvic Dissociation Patterns. AB - Sacral fractures that result in spinopelvic dissociation are unstable injuries that are often treated surgically, with iliosacral screw fixation and/or lumbopelvic fixation from L4 to the pelvis. Open lumbopelvic fixation allows for direct fracture reduction and immediate postoperative weight bearing, but is associated with a relatively high wound complication rate. Open surgery often takes several hours and can be associated with significant blood loss, and therefore may not be well tolerated physiologically in these patients who often have multiple injuries. We developed a percutaneous lumbopelvic reduction and fixation technique to address these issues. PMID- 26894769 TI - Combined Use of Ex Vivo Dermoscopy and Histopathology for the Diagnosis of Melanocytic Tumors. AB - Dermoscopy can be applied to fixed tissues, and dermoscopic patterns correlate with microscopic findings. Data on the influence of ex vivo dermoscopy on pathologic diagnosis of melanocytic lesions are limited. Therefore, we aimed to determine whether this technique could aid on the histopathological evaluation of melanocytic neoplasms. Sequential cutaneous excisional biopsies of melanocytic lesions and their corresponding ex vivo dermoscopic images were prospectively analyzed. Additional sectioning was executed in areas of dermoscopic concern, having, by reference, a dermoscopic mapping of the sectioned specimens. Diagnostic differences before and after analyzing the new dermoscopy-guided sections were registered. A total of 564 melanocytic lesions were examined, and additional cuts were considered necessary in 84 (14.9%) cases. Of these, 11 lesions (13.1%) had a different final diagnosis after dermoscopy-guided specimen sectioning, including 3 lesions that were reclassified as melanomas and 2 melanomas that were restaged. We found that the combined use of ex vivo dermoscopy and histopathology improves clinical-pathological correlation and allows selection of representative areas for sectioning. Altogether, this technique may improve diagnostic confidence and accuracy in the histopathological evaluation of melanocytic lesions. PMID- 26894770 TI - Histopathological Features of Orofacial Granulomatosis. AB - Orofacial granulomatosis (OFG) is characterized by granulomatous inflammation in the orofacial region. Although several series have been reported, biopsy has not been performed in all cases and the histopathological features have not been extensively evaluated. Our purpose was to analyze the histopathological features of our patients with OFG. Twenty-two patients diagnosed with OFG at Bellvitge Hospital (Barcelona, Spain) from 1985 to 2010 were included in the study. All of our patients (14 men and 8 women; mean age 46.77 years, SD 13.61) presented with labial swelling, involving the upper lip in 13 cases and the lower lip in 9 at presentation. Fissured tongue was observed in 9 cases. Three patients suffered facial palsy. Granulomas were observed in 16 patients. All patients showed a perivascular, lymphohistiocytic inflammatory infiltrate with prominent plasma cells in 21 cases. In 5 cases, mast cells were easily observed. In 13 patients, an interstitial infiltrate was also present. All cases showed dilated lymphatic channels, and 19 edema of the lamina propria or the dermis. Perilymphatic granulomas were observed in 12 cases, intralymphatic granulomas in 2, and intralymphatic histiocytes in 2. In conclusion, loose epithelioid cells or lymphonodular granulomas were observed in 73% of our patients. Although none of our patients developed Crohn disease, OFG is histopathologically similar to cutaneous lesions of Crohn disease. The perilymphatic disposition of granulomas and the presence in some cases of intralymphatic histiocytes or intralymphatic granulomas may explain the dilatation of lymphatic vessels and the development of edema. PMID- 26894772 TI - Fluorescence Microscopy as a Diagnostic Tool for Dermatophytosis. AB - Dermatophytosis is a superficial fungal infection of keratinized tissues. Dermatophytes can cause discomfort but are not usually life threatening. However, the infection can spread and may lead to systemic fungal infections in immunocompromised patients. Currently available diagnostic methods include potassium hydroxide (KOH) testing and periodic acid-Schiff (PAS) staining. However, most diagnostic techniques cannot be performed rapidly; days to weeks may be required for conclusive results. Certain dermatophytes autofluoresce and can be observed under fluorescence microscopy. The authors examined a series of 24 cases of hematoxylin and eosin-stained dermatophytoses using fluorescence microscopy and compared the results with those obtained using PAS staining. The diagnostic performance of fluorescence microscopy was better than that of PAS staining. Fluorescence microscopy allowed the detection of all the cases that were detected using PAS staining. In addition, fluorescence microscopy facilitated the detection of weak fluorescence in 2 cases with ambiguous PAS results. These results support the integration into clinical practice of fluorescence microscopy as a simple and rapid diagnostic tool for evaluating cases of suspected dermatophytosis. PMID- 26894771 TI - Protein Expression Analysis of Melanocyte Differentiation Antigen TRP-2. AB - Melanocyte differentiation antigens, such as gp100, tyrosinase, and Melan-A and their corresponding antibodies HMB45, T311, and A103, are major diagnostic tools in surgical pathology. Little is known about tyrosinase-related protein 2 (TRP-2, or dopachrome tautomerase/DCT) another melanocyte differentiation antigen, which is an enzymatic component of melanogenesis. We identified a commercial reagent to TRP-2, monoclonal antibody (mAb) C-9 and undertook a comprehensive analysis to assess its specificity and usefulness for surgical pathology. Subsequently, we analyzed panels of normal tissues and tumors. We show that TRP-2 is regularly expressed in melanocytes of the normal skin. In cutaneous nevi, TRP-2 is present in junctional as well as in dermal nevocytes. In malignant tumors, C-9 reactivity is restricted to melanocytic and related lesions and present in 84% and 58% of primary and metastatic melanomas, respectively. Ten primary melanomas of the anorectal mucosa were all positive. Like the other melanocyte differentiation antigens, TRP-2 was absent in 6 desmoplastic melanomas. Also, only 2 of 9 angiomyolipomas were TRP-2 positive. We conclude that mAb C-9 is a valuable reagent for the analysis of TRP-2 expression in archival surgical pathology material. The expression pattern of TRP-2 in melanocytic and related lesions appears to parallel other melanocyte differentiation antigens, although the overall incidence is lower than other antigens, such as Melan-A or gp100. PMID- 26894773 TI - A Preauricular Ulcer in a Patient With Conjunctival Injection and Persistent Lacrimation: Challenge. PMID- 26894774 TI - Pigmented Porokeratosis. A Further Variant? AB - Porokeratosis is a clonal disorder of keratinization characterized by the presence of the cornoid lamella. A number of variants of porokeratosis have been described, based on the clinical features and histologic features of the lesions. The authors present a case of porokeratosis with prominent melanocytic hyperplasia, which was biopsied to clinically exclude melanoma. The authors retrospectively studied cases of porokeratosis to look for the presence of melanocytic hyperplasia. Melanocytic hyperplasia was identified in 8 of 31 cases (25.8%). All of the cases except the index case were clinically nonpigmented but arose in solar damaged skin. This case represents a distinct variant of porokeratosis, and the authors propose the designation pigmented porokeratosis. Melanocytic hyperplasia is a benign condition, and it is important that this is not histologically confused with melanoma in situ, particularly in a context of clinically pigmented lesion. Increased recognition of pigmented porokeratosis is essential to avoid an erroneous diagnosis of melanoma in situ. PMID- 26894775 TI - Cutaneous Metastases From Malignant Mesothelioma of the Tunica Vaginalis Testis. AB - Mesotheliomas are uncommon tumors arising from mesothelial cells lining the serous membranes of the pleura, pericardium, peritoneum, and tunica vaginalis testis. Less than 100 cases arising from the tunica vaginalis testis have been published and, to our knowledge, only 5 cases of cutaneous involvement from these tumors have been reported. We report an additional case with fatal outcome. A 93 year-old man presented with multiple polypoid nodules on the left scrotum. Ulceration was also present, and a firm 5-cm palpable testicular mass was also found. The patient had been exposed to asbestos for 40 years. Histologic examination of a skin biopsy from one of the nodules showed diffuse dermal infiltration of markedly atypical cuboidal cells, with polymorphous and hyperchromatic nuclei. Mitotic figures were common. These cuboidal cells lined clefts, forming a tubular and micropapillary pattern throughout papillary and reticular dermis. Immunohistochemical study showed strong nuclear and cytoplasmic positivity for calretinin, epithelial membrane antigen (cytoplasmic), and cytokeratin-7 (cytoplasmic) and nuclear positivity for Wilms tumor-1. These findings were consistent with cutaneous infiltration from malignant mesothelioma of the tunica vaginalis testis. Treatment of this rare tumor remains challenging because there are currently no recommended guidelines, but radical inguinal orchiectomy is an optimal choice. PMID- 26894776 TI - Pacinian Corpuscles in a Cervical Chondrocutaneous Remnant: A Case Report and Update of Pacinian Corpuscles. AB - Cervical chondrocutaneous remnants are congenital, benign, and rare neck masses. We present here for the first time the immunohistochemical profile of Pacinian corpuscles present in cervical chondrocutaneous remnants, removed, and localized in the territory of the second branchial arch from a 5-year-old girl. We have performed immunohistochemistry to analyze these sensory corpuscles using a battery of antibodies including markers for each corpuscle constituent. The central axon was immunoreactive for neurofilaments, neuron-specific enolase, and neural cell adhesion molecule; the Schwann-related cells forming the inner core displayed immunoreactivity for S100 protein, vimentin, and neural cell adhesion molecule; the outer core and the capsule were positive for vimentin, epithelial membrane antigen, and glucose transporter 1. These results are discussed in topographical differences. Moreover, a brief update about the structure, protein composition, and development of Pacinian corpuscles was performed. PMID- 26894777 TI - Hair Follicle Miniaturization in a Woolly Hair Nevus: A Novel "Root" Perspective for a Mosaic Hair Disorder. AB - Woolly hair nevus is a mosaic disorder characterized by unruly, tightly curled hair in a circumscribed area of the scalp. This condition may be associated with epidermal nevi. We describe an 11-year-old boy who initially presented with multiple patches of woolly hair and with epidermal nevi on his left cheek and back. He had no nail, teeth, eye, or cardiac abnormalities. Analysis of plucked hairs from patches of woolly hair showed twisting of the hair shaft and an abnormal hair cuticle. Histopathology of a woolly hair patch showed diffuse hair follicle miniaturization with increased vellus hairs. PMID- 26894779 TI - Extramammary Paget Disease of Signet Ring Cell Carcinoma Type: A Case Report. PMID- 26894780 TI - An Extraordinary Manifestation of Nodular Cystic Fat Necrosis. AB - Nodular cystic fat necrosis (NCFN) is characterized by mobile subcutaneous nodules composed of necrotic adipocytes encapsulated by fibrous tissue. The classical presentation of NCFN is solitary or multiple, up to 40, discrete nodules scattered usually on the extremities or trunk. Here, the authors present an elderly woman who developed an unusual and striking clinical picture of NCFN, two months after a fall. The patient had a large indurated plaque and subcutaneous nodule with superposing necrotic ulcers. During debridement of the ulcers, nearly 100 small nodules popped up freely along with a brownish discharge. Deep in the ulcer, the authors discovered a dislocated nail that belongs to an old hip prosthesis. Histopathological findings of the nodules were compatible with NCFN. PMID- 26894781 TI - Metastatic Sarcomatoid Lung Cancer: A Rare Cutaneous Spindle Cell Neoplasm. AB - Cutaneous spindle cell neoplasms can be a diagnostic challenge and may require extensive immunohistochemical staining. The differential diagnoses include melanoma, squamous cell carcinoma, atypical fibrous xanthoma, leiomyosarcoma, dermatofibrosarcoma protuberans, and cutaneous metastases of visceral neoplasms. The authors present a patient with rapidly growing cutaneous nodules in the setting of widespread metastatic disease with clinical suspicion of pulmonary origin. A biopsy demonstrated a poorly differentiated dermal spindle cell neoplasm without overlying epidermal attachment. Immunohistochemical staining demonstrated positivity for cytokeratin wide spectrum screening, cytokeratin-7, CD10, and D2-40. Negative staining was noted for S100, MART-1, SOX-10, CD31, CD45, synaptophysin, chromogranin, CD56, CEA, calretinin, WT-1, HBME-1, TTF-1, and p63. Overall, clinical presentation, histologic pattern, and immunohistochemical profile were consistent with cutaneous metastases of sarcomatoid carcinoma originating in the lung. Diagnosis of sarcomatoid carcinoma can be challenging and requires a carefully select panel of immunohistochemical markers to aid in the accurate diagnosis of this uncommon malignancy and even more rare cutaneous metastatic disease. Sarcomatoid cancer of the lung should be considered in the differential diagnosis of metastatic malignant spindle cell neoplasms. PMID- 26894782 TI - Fluoropyrimidine and platinum toxicity pharmacogenetics: an umbrella review of systematic reviews and meta-analyses. AB - Fluoropyrimidine (FU) and platinum-based chemotherapies are greatly complicated by their associated toxicities. This umbrella systematic review synthesized all systematic reviews that investigated associations between germline variations and toxicity, with the aim of informing personalized medicine. Systematic reviews are important in pharmacogenetics where false positives are common. Four systematic reviews were identified for FU-induced toxicity and three for platinum. Polymorphisms of DPYD and TYMS, but not MTHFR, were statistically significantly associated with FU-induced toxicity (although only DPYD had clinical significance). For platinum, GSTP1 was found to not be associated with toxicity. This umbrella systematic review has synthesized the best available evidence on the pharmacogenetics of FU and platinum toxicity. It provides a useful reference for clinicians and identifies important research gaps. PMID- 26894783 TI - Two-Dimensional Electronic-Vibrational Spectroscopy of Chlorophyll a and b. AB - We present two-dimensional electronic-vibrational (2DEV) spectra of isolated chlorophyll a and b in deuterated ethanol. We excite the Q-band electronic transitions and measure the effects on the carbonyl and C ? C double-bond stretch region of the infrared spectrum. With the aid of density functional theory calculations, we provide assignments for the major features of the spectrum. We show how the 2DEV spectra can be used to readily distinguish different solvation states of the chlorophyll, with features corresponding to the minority pentacoordinate magnesium (Mg) species being resolved along each dimension of the 2DEV spectra from the dominant hexacoordinate Mg species. These assignments represent a crucial first step toward the application of 2DEV spectroscopy to chlorophyll-containing pigment-protein complexes. PMID- 26894785 TI - Series Editors' Notes. PMID- 26894787 TI - Transforming Leadership Development for Significant Learning. AB - Leadership education is undergoing a transformation where powerful pedagogies and emerging knowledge about the scholarship of teaching and learning supplant long held and often-outmoded practices of leadership education. This transformation requires new commitments to evidence-based practice, critical consciousness, and more complex understanding of the levers of leadership learning. PMID- 26894786 TI - Editor's Notes. PMID- 26894784 TI - Macular cystoid spaces in patients with retinal dystrophy. AB - BACKGROUND: Non leaking macular cystoid spaces (MCS) are seen in some retinal dystrophies. Carbonic anhydrase inhibitor (CAI) treatment may reduce the size of MSC and improve vision. METHODS: A retrospective study of patients with retinal dystrophy with MCS seen between 2009 and 2013 at two sites. Patients had ophthalmic examination, optical coherence tomography (OCT) and genetic testing. Patients with vision worse than 20/30 were treated with CAI. Post treatment visual acuity (VA), central foveal zone (CFZ) thickness, and qualitative estimation of MCS size were assessed. RESULTS: Eighteen patients, 6-47 years old, were included. IVFA was performed in 15 (83%) patients. Of the 26 eyes in 13 patients who were treated and followed, VA improved in 15 eyes (58%) of 10 patients. Ten of these 15 eyes had decreased CFZ thickness and 9/10 showed qualitative MCS improvement. Regression analysis showed that change in CFZ thickness was not significantly predictive of change in final visual acuity (p = 0.405). Five of 15 eyes with improved VA had paradoxically increased CFZ thickness and 2/5 had enlarged MCS. Three of the treated eyes (11%) in two patients had decreased VA with decreased CFZ thickness and improved MCS in 2/3 eyes. Eight eyes (31%) in six patients showed no change in VA with decreased CFZ thickness in 6/8 eyes with improved MCS. Genetic testing showed mutations of NR2E3, XLRS, CRB1, GPR98 and CNGB1. CONCLUSION: Non-leaking MCS occur in a variety of retinal dystrophies. Therapy with topical or systemic CAI has variable efficacy and may result in VA improvement with or without qualitative improvement in MCS and CFZ thickness. PMID- 26894788 TI - Building Critical Capacities for Leadership Learning. AB - Cognitive elements of transformational learning, particularly metacognition and critical self-reflection, are discussed as essential considerations for leadership development in the 21st century. The importance of developmentally sequencing leadership-learning experiences and addressing evolving complexities of leadership identity are also explored. PMID- 26894789 TI - Navigating Leadership Complexity Through Critical, Creative, and Practical Thinking. AB - Leadership education that intentionally addresses critical, creative, and practical thinking enhances significant learning for students and deepens the leadership practices of educators. This chapter explores specific applications in the areas of graduate leadership education, action research, service immersion program, and advising conversations. Additionally, it presents a framework of pathways to social change and suggests how such a framework can be useful to students and leadership educators. PMID- 26894790 TI - Integrative and Interdisciplinary Approaches to Leadership Development. AB - Integrating diverse conceptions of leadership across different disciplines, perspectives, and epistemologies is imperative if leaders are to operate in a global and networked world. Interdisciplinary and integrative leadership courses and digital learning communities are featured examples. PMID- 26894791 TI - Valuing Human Significance: Connecting Leadership Development to Personal Competence, Social Competence, and Caring. AB - This chapter examines humanistic ways of understanding learning; connects leadership learning to the concepts of personal competence, social competence, and caring; and introduces the model of emotionally intelligent leadership. PMID- 26894792 TI - Connecting to Experience: High-Impact Practices for Leadership Development. AB - Leadership educators can leverage high-impact experiences to enhance student leadership development. This chapter describes three key practices--sociocultural conversations with peers, mentoring, and membership in off-campus organizations- as levers of leadership learning. Illustrations of the practice in context and reflections from practitioners and students are also included. The chapter concludes with considerations of context, developmental readiness, and best practices of experiential education. PMID- 26894793 TI - Connecting to Communities: Powerful Pedagogies for Leading for Social Change. AB - This chapter explores the use of powerful pedagogies such as service-learning, cultural immersion, and community-based research to enhance leadership development. Four key principles are presented that describe how leadership educators can facilitate community-based learning in a way that creates an optimal learning environment for students, while also engaging ethically with individuals and organizations in the community. PMID- 26894794 TI - Formative Assessment as an Effective Leadership Learning Tool. AB - Formative assessment can be a critical and creative practice in leadership education and significantly enhance student learning, leader development, and leadership development. This chapter seeks to frame the use of assessment as both a best practice in leadership education and as an integral component to effective leadership learning pedagogy. PMID- 26894796 TI - Effect of Organic Matter on Sorption of Zn on Soil: Elucidation by Wien Effect Measurements and EXAFS Spectroscopy. AB - Soil organic matter (SOM) is the major factor affecting sequestration of heavy metals in soil. The mean free binding energy and the mean free adsorption energy and speciation of Zn in soil, as affected by SOM, were determined by employing Wien effect measurements. The presence of SOM markedly decreased the Zn binding energy in soils in the following order: Top (5.86 kJ mol(-1)) < Bottom (8.66 kJ mol(-1)) < Top OM-free (9.44 kJ mol(-1)) ~ Bottom OM-free (9.50 kJ mol(-1)). The SOM also significantly decreased the adsorption energy of Zn on black soil particles by reducing nonspecific adsorption of Zn on their surfaces. The speciation of Zn in soils was elucidated by extended X-ray absorption fine structure spectroscopy and microfocus X-ray fluorescence. The results obtained by linear combination fitting of EXAFS spectra revealed that the main forms of Zn in soil were outer-sphere Zn, Zn-illite, Zn-kaolinite, and HA-Zn. As the SOM content increased, the proportion of HA-Zn among the total immobilized Zn increased, and the proportion of nonspecific adsorbed Zn decreased. The present results implied that SOM is an important controlling factor for the environmental behavior of Zn in soils. PMID- 26894795 TI - Reconstruction of difference in sequential CT studies using penalized likelihood estimation. AB - Characterization of anatomical change and other differences is important in sequential computed tomography (CT) imaging, where a high-fidelity patient specific prior image is typically present, but is not used, in the reconstruction of subsequent anatomical states. Here, we introduce a penalized likelihood (PL) method called reconstruction of difference (RoD) to directly reconstruct a difference image volume using both the current projection data and the (unregistered) prior image integrated into the forward model for the measurement data. The algorithm utilizes an alternating minimization to find both the registration and reconstruction estimates. This formulation allows direct control over the image properties of the difference image, permitting regularization strategies that inhibit noise and structural differences due to inconsistencies between the prior image and the current data. Additionally, if the change is known to be local, RoD allows local acquisition and reconstruction, as opposed to traditional model-based approaches that require a full support field of view (or other modifications). We compared the performance of RoD to a standard PL algorithm, in simulation studies and using test-bench cone-beam CT data. The performances of local and global RoD approaches were similar, with local RoD providing a significant computational speedup. In comparison across a range of data with differing fidelity, the local RoD approach consistently showed lower error (with respect to a truth image) than PL in both noisy data and sparsely sampled projection scenarios. In a study of the prior image registration performance of RoD, a clinically reasonable capture ranges were demonstrated. Lastly, the registration algorithm had a broad capture range and the error for reconstruction of CT data was 35% and 20% less than filtered back-projection for RoD and PL, respectively. The RoD has potential for delivering high-quality difference images in a range of sequential clinical scenarios including image guided surgeries and treatments where accurate and quantitative assessments of anatomical change is desired. PMID- 26894797 TI - Structure, function and carcinogenicity of metabolites of methylated and non methylated polycyclic aromatic hydrocarbons: a comprehensive review. AB - The Unified Theory of PAH Carcinogenicity accommodates the activities of methylated and non-methylated polycyclic aromatic hydrocarbons (PAHs) and states that substitution of methyl groups on meso-methyl substituted PAHs with hydroxy, acetoxy, chloride, bromide or sulfuric acid ester groups imparts potent cancer producing properties. It incorporates specific predictions from past researchers on the mechanism of carcinogenesis by methyl-substituted hydrocarbons, including (1) requirement for metabolism to an ArCH2X type structure where X is a good leaving group and (2) biological substitution of a meso-methyl group at the most reactive center in non-methylated hydrocarbons. The Theory incorporates strong inferences of Fieser: (1) The mechanism of carcinogenesis involves a specific metabolic substitution of a hydrocarbon at its most reactive center and (2) Metabolic elimination of a carcinogen is a detoxifying process competitive with that of carcinogenesis and occurring by a different mechanism. According to this outlook, chemical or biochemical substitution of a methyl group at the reactive meso-position of non-methylated hydrocarbons is the first step in the mechanism of carcinogenesis for most, if not all, PAHs and the most potent metabolites of PAHs are to be found among the meso methyl-substituted hydrocarbons. Some PAHs and their known or potential metabolites and closely related compounds have been tested in rats for production of sarcomas at the site of subcutaneous injection and the results strongly support the specific predictions of the Unified Theory. PMID- 26894799 TI - The Safety of Erythropoiesis-Stimulating Agents for the Treatment of Anemia Resulting from Chronic Kidney Disease. AB - Chronic kidney disease (CKD) anemia treatment was revolutionized in the late 1980s with the introduction of recombinant human erythropoietin. This and related erythropoiesis-stimulating agents (ESAs) greatly benefited patients by decreasing debilitating symptoms, improving their quality of life, and freeing them from dependence on blood transfusions with their associated complications such as infections, sensitization impeding transplantation, and secondary iron overload. However, even in the initial studies, untoward effects were noted in patients receiving ESAs, including worsening hypertension, seizures, and dialysis access clotting. Later, increased mortality, malignancy progression and even stroke were reported in renal patients. This review focuses on the safety issues of ESAs in CKD patients. PMID- 26894801 TI - Pain Management for Gynecologic Procedures in the Office. AB - IMPORTANCE: Satisfactory pain control for women undergoing office gynecologic procedures is critical for both patient comfort and procedure success. Therefore, it is important for clinicians to be aware of the safety and efficacy of different pain control regimens. OBJECTIVE: This article aimed to review the literature regarding pain control regimens for procedures such as endometrial biopsy, intrauterine device insertion, colposcopy and loop electrosurgical excisional procedure, uterine aspiration, and hysteroscopy. EVIDENCE ACQUISITION: A search of published literature using PubMed was conducted using the following keywords: "pain" or "anesthesia." These terms were paired with the following keywords: "intrauterine device" or "IUD," "endometrial biopsy," "uterine aspiration" or "abortion," "colposcopy" or "loop electrosurgical excisional procedure" or "LEEP," "hysteroscopy" or "hysteroscopic sterilization." The search was conducted through July 2015. Articles were hand reviewed and selected by the authors for study quality. Meta-analyses and randomized controlled trials were prioritized. RESULTS: Although local anesthesia is commonly used for gynecologic procedures, a multimodal approach may be more effective including oral medication, a dedicated emotional support person, and visual or auditory distraction. Women who are nulliparous, are postmenopausal, have a history of dysmenorrhea, or suffer from anxiety are more likely to experience greater pain with gynecologic procedures. Evidence for some interventions exists; however, the interpretation of intervention comparisons is limited by the use of different regimens, pain measurement scales, patient populations, and procedure techniques. CONCLUSIONS AND RELEVANCE: There are many options for pain management for office gynecologic procedures, and depending on the procedure, different modalities may work best. The importance of patient counseling and selection cannot be overstated. PMID- 26894800 TI - Type 2 Diabetes Patients Reach Target Glycemic Control Faster Using IDegLira than Either Insulin Degludec or Liraglutide Given Alone. AB - BACKGROUND AND OBJECTIVES: The time-course when changes in glycemic control and body weight were first manifest in patients with type 2 diabetes mellitus (T2DM) treated with a combination of insulin degludec and liraglutide (IDegLira) was assessed, comparing IDegLira to its individual components. METHODS: Data from weeks 0-12 from two studies were analyzed, one comparing IDegLira to each component (DUAL I), and one comparing IDegLira to insulin degludec titrated to a maximum 50 units (DUAL II). Efficacy endpoints included glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG) reduction, proportion of patients achieving HbA1c [<7.0 % (<53.0 mmol/mol)] and FPG (<=7.2 mmol/L) targets, and proportion achieving HbA1c target without hypoglycemia and without hypoglycemia and weight gain. RESULTS: Mean HbA1c was lower, and the proportion of patients reaching target HbA1c greater, with IDegLira versus comparators (both studies) at weeks 8 and 12. Proportions of patients reaching target HbA1c without hypoglycemia and without hypoglycemia and weight gain were higher for IDegLira versus insulin degludec, though not versus liraglutide. Mean FPG was lower with IDegLira, and the proportion achieving target FPG higher, versus components (both studies) from weeks 4-12. IDegLira was associated with mean weight reduction from weeks 4-12, although less than with liraglutide alone. Hypoglycemia occurred infrequently in weeks 0-12, with no difference in incidence between IDegLira and insulin degludec in either study. CONCLUSIONS: IDegLira reduces plasma glucose to a greater extent than its components, measurable within the first 12 weeks of therapy, and without weight gain or an increased hypoglycemia risk versus insulin degludec. PMID- 26894802 TI - Procedures and Uterine-Sparing Surgeries for Managing Postpartum Hemorrhage: A Systematic Review. AB - IMPORTANCE: Postpartum hemorrhage (PPH) is one of the leading causes of maternal mortality and morbidity worldwide. OBJECTIVE: The aim of this study was to systematically review literature on procedures (eg, uterine artery embolization) and uterine-sparing surgeries for PPH. EVIDENCE ACQUISITION: We searched MEDLINE and other databases from 1990 to November 2014. Two reviewers independently evaluated studies against predetermined criteria, extracted data, and assessed study quality and strength of the evidence (confidence in the effect). RESULTS: Twenty-eight small studies addressed 1 or more procedures (19 studies of embolization, 5 of uterine tamponade) or surgeries (5 studies of arterial ligation, 5 of uterine compression sutures). Studies primarily evaluated bleeding control and adverse effects. Rates of hemostasis were typically greater than 60% in studies reporting such data after failure of conservative management. Postprocedure infertility occurred in 0% to 43% of women in a small number of studies that reported these data. Uterine tamponade successfully controlled bleeding in more than 50% of women, with few harms reported. Success rates for ligation and sutures ranged from 36% to 96%; harms included surgical injury, infection, and fertility-associated effects. CONCLUSIONS AND RELEVANCE: A limited body of evidence addresses these interventions for PPH. Median rates of hemostasis ranged from 36% to 98%; however, these data come from few studies with less than 2100 total participants. Harms were not well characterized. Some studies with longer-term follow-up reported infertility in women undergoing embolization. Few adverse events with tamponade, ligation, or sutures were reported. Given the insufficient evidence, clinicians must continue to make individual care decisions based on each woman's clinical situation and available management options. PMID- 26894803 TI - Obesity and Pelvic Floor Dysfunction: Battling the Bulge. AB - IMPORTANCE: Pelvic floor disorders (PFDs) comprise a broad spectrum of clinical conditions, including urinary incontinence, pelvic organ prolapse, fecal incontinence, and defecatory dysfunction. These disorders are common conditions that generate significant medical, emotional, social, and economic issues for many women. Obese women are disproportionately affected compared with their normal-weight peers, with more than half of women with a body mass index of greater than 35 kg/m(2) reporting a PFD, compared with only 32% in women with a normal body mass index. Despite this prevalence, little research is available to help guide and tailor treatment in obese populations. OBJECTIVE: This review outlines current knowledge regarding the relative contribution of obesity to PFDs, as well as its effect on treatment implications. EVIDENCE ACQUISITION: Literature relating to the incidence and treatment of PFDs in obese populations was reviewed. RESULTS: Both nonsurgical and surgical weight loss improves all PFDs. Obese women benefit from pelvic floor training, biofeedback, and pharmacologic treatments of urinary and fecal incontinence. Surgical treatments of stress urinary incontinence note increased operative times and perhaps slightly lower cure rates, but overall good treatment success in obese women. No increased risks of complications or treatment failure were noted in obese women treated for prolapse surgically, and pessaries work well for both prolapse and stress urinary incontinence in obese women. CONCLUSIONS/RELEVANCE: Although literature regarding treatment of PFDs in obese women is limited, the available evidence demonstrates good treatment outcomes in obese populations. Further research into how to best counsel and optimize treatment of obese patients is essential as the obesity epidemic continues. PMID- 26894805 TI - Should Physicians Attempt to Persuade a Patient to Accept a Compromised Organ for Transplant? PMID- 26894806 TI - How to Communicate Clearly about Brain Death and First-Person Consent to Donate. PMID- 26894804 TI - Analgesic use and the risk of primary adult brain tumor. AB - Glioma and meningioma are uncommon tumors of the brain with few known risk factors. Regular use of aspirin has been linked to a lower risk of gastrointestinal and other cancers, though evidence for an association with brain tumors is mixed. We examined the association of aspirin and other analgesics with the risk of glioma and meningioma in a large US case-control study. Cases were persons recently diagnosed with glioma or meningioma and treated at medical centers in the southeastern US. Controls were persons sampled from the same communities as the cases combined with friends and other associates of the cases. Information on past use of analgesics (aspirin, other anti-inflammatory agents, and acetaminophen) was collected in structured interviews. Logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for analgesic use adjusted for potential confounders. All associations were considered according to indication for use. A total of 1123 glioma cases, 310 meningioma cases and 1296 controls were included in the analysis. For indications other than headache, glioma cases were less likely than controls to report regular use of aspirin (OR 0.69; CI 0.56, 0.87), in a dose-dependent manner (P trend < 0.001). No significant associations were observed with other analgesics for glioma, or any class of pain reliever for meningioma. Results suggest that regular aspirin use may reduce incidence of glioma. PMID- 26894808 TI - Ethical Dilemmas in Liver Transplant Organ Allocation: Is it Time for a New Mathematical Model? PMID- 26894807 TI - Can Social Media Help Increase the Organ Supply While Avoiding Exploitation and Trafficking? PMID- 26894809 TI - Regulations' Impact on Donor and Recipient Selection for Liver Transplantation: How Should Outcomes be Measured and MELD Exception Scores be Considered? PMID- 26894810 TI - Technology- and Policy-Based Strategies for Increasing Supply of Deceased Donor Livers. PMID- 26894811 TI - Elective Transplantation for MMA Patients: How Ought Patients' Needs for Organs to be Prioritized when Transplantation Is Not their Only Available Treatment? PMID- 26894812 TI - Organ Donation as a Collective Action Problem: Ethical Considerations and Implications for Practice. PMID- 26894813 TI - Ethical Considerations of Transplantation and Living Donation for Patients with Alcoholic Liver Diseases. PMID- 26894814 TI - Impact of Elevated Hemoglobin and Serum Protein on Vasovagal Reaction from Blood Donation. AB - We conducted a cross-sectional study to elucidate factors contributing to vasovagal reaction (VVR), the most frequent side effect following whole blood and apheresis donations. Complications recorded at the collection sites after voluntary donations by the Japanese Red Cross Tokyo Blood Center (JRC), in the 2006 and 2007 fiscal years, were analyzed by both univariate analysis and the multivariate conditional logistic regression model. Of 1,119,716 blood donations over the full two years, complications were recorded for 13,320 donations (1.18%), among which 67% were VVR. There were 4,303 VVR cases which had sufficient information and could be used for this study. For each VVR case, two sex- and age-matched controls (n = 8,606) were randomly selected from the donors without complications. Age, sex, body mass index (BMI), predonation blood pressure, pulse and blood test results, including total protein, albumin, and hemoglobin, were compared between the VVR group and the control group. In univariate analysis, the VVR group was significantly younger, with a lower BMI, higher blood pressure and higher blood protein and hemoglobin levels than the control group (p<0.001). Furthermore, blood protein and hemoglobin levels showed dose-dependent relationships with VVR incidences by the Cochran-Armitage trend test (p<0.01). For both sexes, after adjusting for confounders with the multivariate conditional logistic regression model, the higher than median groups for total protein (male: OR 1.97; 95%CI 1.76,-2.21; female: OR 2.29; 95%CI 2.05 2.56), albumin (male: 1.75; 1.55-1.96; female: 1.76; 1.57-1.97) and hemoglobin (male: 1.98; 1.76-2.22; female: 1.62; 1.45-1.81) had statistically significant higher risk of VVR compared to the lower than median groups. These elevated serum protein and hemoglobin levels might offer new indicators to help understand VVR occurrence. PMID- 26894815 TI - Long term effects of traffic noise on mortality in the city of Barcelona, 2004 2007. AB - Numerous studies showing statistically significant associations between environmental noise and adverse health effects already exist for short-term (over one day at most) and long-term (over a year or more) noise exposure, both for morbidity and (albeit to a lesser extent) mortality. Recently, several studies have shown this association to be independent from confounders, mainly those of air pollutants. However, what has not been addressed is the problem of misalignment (i.e. the exposure data locations and health outcomes have different spatial locations). Without any explicit control of such misalignment inference is seriously compromised. Our objective is to assess the long-term effects of traffic noise on mortality in the city of Barcelona (Spain) during 2004-2007. We take into account the control of confounding, for both air pollution and socioeconomic factors at a contextual level and, in particular, we explicitly address the problem of misalignment. We employed a case-control design with individual data. We used deaths resulting from myocardial infarction, hypertension, or Type II diabetes mellitus in Barcelona between 2004 and 2007 as cases for the study, while for controls we used deaths (likewise in Barcelona and over the same period of time) resulting from AIDS or external causes (e.g. accidental falls, accidental poisoning by psychotropic drugs, drugs of abuse, suicide and self-harm, or injuries resulting from motor vehicle accidents). The controls were matched with the cases by sex and age. We used the annual average equivalent A-weighted sound pressure levels for daytime (7-21h), evening-time (21 23h) and night-time (23-7h), and controlled for the following confounders: i) air pollutants (NO2, PM10 and benzene), ii) material deprivation (at a census tract level) and iii) land use and other spatial variables. We explicitly controlled for heterogeneity (uneven distribution of both response and environmental exposures within an area), spatial dependency (of the observations of the response variables), temporal trends (long-term behaviour of the response variables) and spatial misalignment (between response and environmental exposure locations). We used a fully Bayesian method, through the Integrated Nested Laplace Approximation (INLA). Specifically, we plugged the whole model for the exposure into the health model and obtained a linear predictor defined on the entire spatial domain. Separate analyses were carried out for men and for women. After adjusting for confounders, we found that traffic noise was associated with myocardial infarction mortality along with Type II diabetes mellitus in men (in both cases, odds ratios (OR) were around 1.02) and mortality from hypertension in women (ORs around 1.01). Nevertheless, only in the case of hypertension in women, does the association remain statistically significant for all age groups considered (all ages, >=65 years and >=75 years). PMID- 26894817 TI - "We have to ask and only then do": Unpacking agency and autonomy in women's reproductive health in urban India. AB - The limited autonomy and agency of women in developing countries is recognized as a key barrier to improving their reproductive health. Using an existing perinatal cohort in urban South India, we interviewed 36 women who had recently been through childbirth, and we carried out observations of family life and clinic encounters. Critical domains involved in women's agency and autonomy were women's participation in employment and group action and their mobility. Household decision making was considered a joint rather than individual responsibility. We call for a more nuanced understanding of these domains and their relationship to women's reproductive health, particularly for urban populations. PMID- 26894816 TI - Feasibility of hair sampling to assess levels of organophosphate metabolites in rural areas of Sri Lanka. AB - Measuring chronic pesticide exposure is important in order to investigate the associated health effects. Traditional biological samples (blood/urine) are difficult to collect, store and transport in large epidemiological studies in settings such as rural Asia. We assessed the acceptability of collecting hair samples from a rural Sri Lankan population and found that this method of data collection was feasible. We also assessed the level of non-specific metabolites (DAPS) of organophosphate pesticides in the hair samples. The median concentration (pg/mg) of each DAP was: diethyl phosphate: 83.3 (IQI 56.0, 209.4); diethyl thiophosphate: 34.7 (IQI 13.8, 147.9); diethyl dithiophosphate: 34.5 (IQI 23.4, 55.2); and dimethyl phosphate: 3 (IQI 3, 109.7). Total diethylphosphates were recovered in >80% of samples and were positively correlated with self reported pesticide exposure. PMID- 26894819 TI - Spin-Orbit Coupling Effects in AumPtn Clusters (m + n = 4). AB - A study of AumPtn(m + n = 4) clusters with and without spin-orbit (SO) coupling using scalar relativistic (SR) and two component methods with the ZORA Hamiltonian was carried out. We employed the PW91 functional in conjunction with the all-electron TZ2P basis set. This paper offers a detailed analysis of the SO effects on the cluster geometries, on the LUMO-HOMO gap, on the charge distribution, and on the relative energies for each relativistic method. In general, SO coupling led to an energetic rearrangement of the species, to changes in geometries and structural preferences, to changes in the structural identity of the global minimum for the Au3Pt, AuPt3 and Pt4 cases, and to a reduction of relative energies among the clusters, an effect that appears stronger as the amount of Pt increases. PMID- 26894818 TI - Anti-inflammatory and blood stasis activities of essential oil extracted from Artemisia argyi leaf in animals. AB - Artemisia argyi leaf is a well-known species in traditional Chinese medicine. However, the anti-inflammatory and activating blood stasis activities of its essential oil (AAEO) have not been explored in vivo. The present study measured the contents of three chemical components by gas chromatography (GC). The anti acute inflammatory effects of AAEO were investigated in dimethyl benzene, glacial acetic acid and carrageenan-induced animals through skin administration or by oral gavage, respectively. The effects of AAEO on haemorheology were studied in a rat acute blood stasis model. The contents of eucalyptol, camphor and borneol in AAEO were 254.4, 51.6 and 58.7 mg/g, respectively. All dosages of AAEO by skin administration significantly decreased the swelling in dimethyl benzene-induced ear oedema and carrageenan-induced paw oedema, and reduced the permeability in glacial acetic acid-induced abdominal blood capillary (p < 0.01). Meanwhile, haemorheology indexes such as whole blood viscosity and the erythrocyte aggregation index significantly decreased only in the high dosage group. In addition, the effects of AAEO by oral gavage were weaker than skin administration at the medium dose in the experiments. It suggests that AAEO has better absorption bioavailability and pharmacological effects through skin administration due to the better skin permeability of essential oil than gastrointestinal absorption. PMID- 26894820 TI - What Factors Are Associated with Positive Effects of Dog Ownership in Families with Children with Autism Spectrum Disorder? The Development of the Lincoln Autism Pet Dog Impact Scale. AB - Scientific literature exploring the value of assistance dogs to children with autism spectrum disorder (ASD) is rapidly emerging. However, there is comparably less literature reporting the effects of pet (as opposed to assistance) dogs to these children. In particular, there are no known validated scales which assess how children may alter their behaviours in the presence of the dog, to evaluate the efficacy of pet dogs to these families. Additionally, given the highly individualised nature of ASD it is likely that some children and families gain more benefits from dog ownership than others, yet no research has reported the effect of individual differences. This pilot study reports the development of a 28-item scale based on the perceived impact of a pet dog on a child with autism by parents (Lincoln Autism Pet Dog Impact Scale--LAPDIS). The scale is comprised of three mathematically derived factors: Adaptability, Social Skills and Conflict Management. We assessed how individual differences (aspects) may be associated with scores on these three factors. Family Aspects and Dog Aspects were not significantly associated with ratings on the three factors, but Child Aspects (including: contact with horses, child age, disability level and language abilities) were related to impact of the dog on all factors. Training Aspects were related to scores on Social Skills (formal training with children with ASD and dogs and attendance at PAWS workshops run by Dogs for Good). These results suggest that individual differences associated with the child and the training approach may be important considerations for a positive impact from dog ownership on families with children with ASD. Differences in family features and the dog may not be so important, but may be worthy of further investigations given the early stage of development in this field. PMID- 26894821 TI - Evaluation of Enrichment Protocols for Bacterial Endosymbionts of Ciliates by Real-Time PCR. AB - Large-scale studies on obligate bacterial endosymbionts may frequently require preliminary purification and enrichment protocols, which are often elaborate to set up and to evaluate, especially if the host organism is a protist. The purpose of this study was to develop a real-time PCR-based strategy and employ it for assessing two of such enrichment protocols for Holospora caryophila, hosted by the ciliate Paramecium. Four SSU rRNA gene-targeted real-time PCR assays were designed, which allowed to compare the amount of H. caryophila to other organisms, namely the host, its food bacterium (Raoultella planticola), and free living bacteria present in the culture medium. By the use of the real-time PCR assays in combination, it was possible to conclude that the "cell fractionation" protocol was quite successful in the enrichment of the symbiont, while the "Percoll gradient" protocol will need further refinements to be fully repeatable. The proposed approach has the potential to facilitate and encourage future studies on the yet underexplored field of bacterial endosymbionts of ciliates and other protists. It can also find valuable applications for experimental questions other than those tested, such as fast and precise assessment of symbiont abundance in natural populations and comparison among multiple coexisting symbionts. PMID- 26894823 TI - Clinical and Pharmacologic Considerations for Guanfacine Use in Very Young Children. AB - OBJECTIVE: Guanfacine, in the immediate release form, remains a commonly used medication for the treatment of clinically significant hyperactivity, impulsivity, or disruptive behaviors. This article reviews the available literature regarding guanfacine use in very young children (<6 years of age), and explores some of the factors that may uniquely impact the clinical pharmacology of guanfacine in very young children and that deserve consideration when it is used in this patient population. METHODS: The authors performed electronic literature searches in PubMed through October 2015 using the terms attention deficit/hyperactivity disorder, guanfacine, and alpha agonists. We also performed an informal review of the literature and used selected articles from relevant reference lists. The result was a broad, qualitative review of the literature, with a focus on specific factors regarding guanfacine use in very young children. RESULTS: Despite the fact that guanfacine is commonly used in very young children, there is a paucity of published studies that looked specifically at its use in this population. In reviewing the pharmacology of guanfacine, there are specific factors that may play a unique role in its disposition in very young children. CONCLUSIONS: Guanfacine is an important medication option in very young children; however, there is a significant pharmacologic "information gap," and further research is needed to help establish appropriate, safe, and effective dosing of guanfacine in this population. PMID- 26894822 TI - A randomized, placebo-controlled proof-of-concept trial of adjunctive topiramate for alcohol use disorders in bipolar disorder. AB - BACKGROUND AND OBJECTIVES: Topiramate is effective for alcohol use disorders (AUDs) among non-psychiatric patients. We examined topiramate for treating comorbid AUDs in bipolar disorder (BD). METHODS: Twelve participants were randomized to topiramate or placebo for 12 weeks. RESULTS: The topiramate group, with two out of five participants (40%) completing treatment, experienced less improvement in drinking patterns than the placebo group, with five out of seven participants (71%) completing treatment. DISCUSSION AND CONCLUSIONS: Topiramate did not improve drinking behavior and was not well-tolerated. This study failed to recruit adequately. Problems surrounding high attrition, a small study sample, and missing data preclude interpretation of study findings. SCIENTIFIC SIGNIFICANCE: This is the first randomized, placebo-controlled trial of topiramate for AUDs in BD. PMID- 26894824 TI - Analysis of palatal rugae in males and females of an average age of 35 in a population from Bosnia and Herzegovina (Sarajevo Canton). AB - The goal of this study is to identify and compare palatal rugae patterns in males and females of an average age of 35 in a sample population from Bosnia and Herzegovina (Sarajevo Canton), as an additional method for sex differentiation in various situations. The research did not determine any statistically significant difference in the total number of palatal rugae between the sexes, which is in line with previous research. However, in the case of the number of secondary palatal rugae where the probability of an equal average is slightly higher than the tolerance of 5%, the difference being 7.6% which may indicate that secondary palatal rugae are more common in women. However, logistic regression analysis LRA is still more successful in classifying males, 69% of them, while for women the success rate is significantly lower with only 41%. In total, 55% of subjects were correctly classified. It may be concluded that using LRA in palatal rugae could be used as an additional sex differentiation method for the population of Bosnia and Herzegovina. PMID- 26894826 TI - System-Wide Mapping of Activated Circuitry in Experimental Systemic Inflammatory Response Syndrome: Erratum. AB - In the article on pages 148-156 of the February 2016 issue, the labeling of Module 1 and Module 2 in Figure 3 is reversed. The text in the highlighted red box should read: "SIRS-associated Module 1 (Please refer to Figure 6 for details)"; the label in blue color above the network should read: "SIRS-associaed Module 2." PMID- 26894825 TI - Biventricular mechanical support devices--clinical perspectives. AB - Cardiac transplantation remains the optimal treatment for end stage heart failure in selected patients. However, the shortage of donor hearts, rigorous eligibility criteria and long waiting lists have increased the demand for alternative treatment strategies such as mechanical circulatory support. While many patients are adequately supported with left ventricular assist devices, frequently there is right heart failure or involvement of the right ventricle, requiring biventricular support. Pulsatile flow biventricular devices and total artificial hearts approved for temporary biventricular support have limitations including size, high rates of adverse events and restricted mobility which makes them unsuitable for long term support. A number of centres have reported dual continuous flow left ventricular assist devices as a means of supporting the left and right heart. This review will summarise the literature on the outcomes and complications from current biventricular support devices and assess the role of dual continuous flow VAD therapy, and the new continuous flow total heart replacement devices. PMID- 26894827 TI - Systematic and Dramatic Tuning on Gas Sorption Performance in Heterometallic Metal-Organic Frameworks. AB - Despite their having much greater potential for compositional and structural diversity, heterometallic metal-organic frameworks (MOFs) reported so far have lagged far behind their homometallic counterparts in terms of CO2 uptake performance. Now the power of heterometallic MOFs is in full display, as shown by a series of new materials (denoted CPM-200s) with superior CO2 uptake capacity (up to 207.6 cm(3)/g at 273 K and 1 bar), close to the all-time record set by MOF 74-Mg. The isosteric heat of adsorption can also be tuned from -16.4 kJ/mol for CPM-200-Sc/Mg to -79.6 kJ/mol for CPM-200-V/Mg. The latter value is the highest reported for MOFs with Lewis acid sites. Some members of the CPM-200s family consist of combinations of metal ions (e.g., Mg/Ga, Mg/Fe, Mg/V, Mg/Sc) that have never been shown to coexist in any known crystalline porous materials. Such previously unseen combinations become reality through a cooperative crystallization process, which leads to the most intimate form of integration between even highly dissimilar metals, such as Mg(2+) and V(3+). The synergistic effects of heterometals bestow CPM-200s with the highest CO2 uptake capacity among known heterometallic MOFs and place them in striking distance of the all time CO2 uptake record. PMID- 26894830 TI - Olodaterol + tiotropium bromide for the treatment of COPD. AB - Patients suffering from COPD not controlled by a single bronchodilator should be given two bronchodilators with different mechanisms of action. Addition of a LABA to a LAMA induces a larger bronchodilation than that obtained with the LAMA as monotherapy and also improves many patient-reported outcomes. Since the clinical functional sign regarding simultaneous use of tiotropium, which is still the dominant LAMA, and olodaterol was very strong, the combination of these two bronchodilators has been developed as FDC delivered via a single inhaler (Respimat) with the aim of simplifying the treatment regimen and improving patient adherence to treatment. The large TOviTO program of Phase III clinical trials that is involving more than 15,000 patients with different levels of COPD severity worldwide and includes several clinical studies is documenting the efficacy and safety of tiotropium/olodaterol FDC as maintenance therapy in patients with moderate to very severe COPD. PMID- 26894829 TI - Genetic Testing and the Workplace. PMID- 26894828 TI - Agent Based Modeling of Human Gut Microbiome Interactions and Perturbations. AB - BACKGROUND: Intestinal microbiota plays an important role in the human health. It is involved in the digestion and protects the host against external pathogens. Examination of the intestinal microbiome interactions is required for understanding of the community influence on host health. Studies of the microbiome can provide insight on methods of improving health, including specific clinical procedures for individual microbial community composition modification and microbiota correction by colonizing with new bacterial species or dietary changes. METHODOLOGY/PRINCIPAL FINDINGS: In this work we report an agent-based model of interactions between two bacterial species and between species and the gut. The model is based on reactions describing bacterial fermentation of polysaccharides to acetate and propionate and fermentation of acetate to butyrate. Antibiotic treatment was chosen as disturbance factor and used to investigate stability of the system. System recovery after antibiotic treatment was analyzed as dependence on quantity of feedback interactions inside the community, therapy duration and amount of antibiotics. Bacterial species are known to mutate and acquire resistance to the antibiotics. The ability to mutate was considered to be a stochastic process, under this suggestion ratio of sensitive to resistant bacteria was calculated during antibiotic therapy and recovery. CONCLUSION/SIGNIFICANCE: The model confirms a hypothesis of feedbacks mechanisms necessity for providing functionality and stability of the system after disturbance. High fraction of bacterial community was shown to mutate during antibiotic treatment, though sensitive strains could become dominating after recovery. The recovery of sensitive strains is explained by fitness cost of the resistance. The model demonstrates not only quantitative dynamics of bacterial species, but also gives an ability to observe the emergent spatial structure and its alteration, depending on various feedback mechanisms. Visual version of the model shows that spatial structure is a key factor, which helps bacteria to survive and to adapt to changed environmental conditions. PMID- 26894833 TI - A Collaborative Strategy to Bring Evidence into Practice. PMID- 26894832 TI - Focal Length Affects Depicted Shape and Perception of Facial Images. AB - Static photographs are currently the most often employed stimuli in research on social perception. The method of photograph acquisition might affect the depicted subject's facial appearance and thus also the impression of such stimuli. An important factor influencing the resulting photograph is focal length, as different focal lengths produce various levels of image distortion. Here we tested whether different focal lengths (50, 85, 105 mm) affect depicted shape and perception of female and male faces. We collected three portrait photographs of 45 (22 females, 23 males) participants under standardized conditions and camera setting varying only in the focal length. Subsequently, the three photographs from each individual were shown on screen in a randomized order using a 3 alternative forced-choice paradigm. The images were judged for attractiveness, dominance, and femininity/masculinity by 369 raters (193 females, 176 males). Facial width-to-height ratio (fWHR) was measured from each photograph and overall facial shape was analysed employing geometric morphometric methods (GMM). Our results showed that photographs taken with 50 mm focal length were rated as significantly less feminine/masculine, attractive, and dominant compared to the images taken with longer focal lengths. Further, shorter focal lengths produced faces with smaller fWHR. Subsequent GMM revealed focal length significantly affected overall facial shape of the photographed subjects. Thus methodology of photograph acquisition, focal length in this case, can significantly affect results of studies using photographic stimuli perhaps due to different levels of perspective distortion that influence shapes and proportions of morphological traits. PMID- 26894831 TI - Embryo Aggregation in Pig Improves Cloning Efficiency and Embryo Quality. AB - In this study, we analyzed the effects of the cloned embryo aggregation on in vitro embryo development and embryo quality by measuring blastocyst diameter and cell number, DNA fragmentation levels and the expression of genes associated with pluripotency, apoptosis, trophoblast and DNA methylation in the porcine. Zona free reconstructed cloned embryos were cultured in the well of the well system, placing one (1x non aggregated group) or three (3x group) embryos per microwell. Our results showed that aggregation of three embryos increased blastocyst formation rate and blastocyst diameter of cloned pig embryos. DNA fragmentation levels in 3x aggregated cloned blastocysts were significantly decreased compared to 1x blastocysts. Levels of Oct4, Klf4, Igf2, Bax and Dnmt 1 transcripts were significantly higher in aggregated embryos, whereas Nanog levels were not affected. Transcripts of Cdx2 and Bcl-xl were essentially non-detectable. Our study suggests that embryo aggregation in the porcine may be beneficial for cloned embryo development and embryo quality, through a reduction in apoptotic levels and an improvement in cell reprogramming. PMID- 26894835 TI - NGMSElectTM and Investigator((r)) Argus X-12 analysis in population samples from Albania, Iraq, Lithuania, Slovenia, and Turkey. AB - The analysis of STRs is the main tool when studying genetic diversity in populations or when addressing individual identification in forensic casework. Population data are needed to establish reference databases that can be used in the forensic context. To that end, this work investigated five population samples from Albania, Iraq, Lithuania, Slovenia, and Turkey. Individuals were typed for 16 autosomal STRs and 12 X-chromosomal STRs using the NGMSElectTM and Investigator((r)) Argus X-12 kits, respectively. The aim of the study was to characterize the diversity of both STR kits in these population samples and to expand our forensic database. The results showed that all markers were polymorphic in the five populations studied. No haplotype was shared between the males analysed for X-STRs. No statistically significant deviations from Hardy Weinberg equilibrium were observed for any of the genetic markers included in both the kits. Pairwise LD was only detected in X-STRs between markers located in the same linkage group. Power of discrimination values for males and females and the probability of exclusion in duos and trios were high for the populations in this study. PMID- 26894834 TI - Two Small Molecules Block Oral Epithelial Cell Invasion by Porphyromons gingivalis. AB - Porphyromonas gingivalis is a keystone pathogen of periodontitis. One of its bacterial characteristics is the ability to invade various host cells, including nonphagocytic epithelial cells and fibroblasts, which is known to facilitate P. gingivalis adaptation and survival in the gingival environment. In this study, we investigated two small compounds, Alop1 and dynasore, for their role in inhibition of P. gingivalis invasion. Using confocal microscopy, we showed that these two compounds significantly reduced invasion of P. gingivalis and its outer membrane vesicles into human oral keratinocytes in a dose-dependent manner. The inhibitory effects of dynasore, a dynamin inhibitor, on the bacterial entry is consistent with the notion that P. gingivalis invasion is mediated by a clathrin mediated endocytic machinery. We also observed that microtubule arrangement, but not actin, was altered in the host cells treated with Alop1 or dynasore, suggesting an involvement of microtubule in this inhibitory activity. This work provides an opportunity to develop compounds against P. gingivalis infection. PMID- 26894837 TI - Substrate-Controlled Product Divergence: Conversion of CO2 into Heterocyclic Products. AB - Substituted epoxy alcohols and amines allow substrate-controlled conversion of CO2 into a wide range of heterocyclic structures through different mechanistic manifolds. This new approach results in an unusual scope of CO2-derived products by initial activation of CO2 through either the amine or alcohol unit, thus providing nucleophiles for intramolecular epoxy ring opening under mild reaction conditions. Control experiments support the crucial role of the amine/alcohol fragment in this process with the nucleophile-assisted ring-opening step following an SN i pathway, and a 5-exo-tet cyclization, thus leading to heterocyclic scaffolds. PMID- 26894836 TI - Programmed Self-Assembly of an Active P22-Cas9 Nanocarrier System. AB - Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) RNA-guided endonucleases are powerful new tools for targeted genome engineering. These nucleases provide an efficient and precise method for manipulating eukaryotic genomes; however, delivery of these reagents to specific cell-types remains challenging. Virus-like particles (VLPs) derived from bacteriophage P22, are robust supramolecular protein cage structures with demonstrated utility for cell type-specific delivery of encapsulated cargos. Here, we genetically fuse Cas9 to a truncated form of the P22 scaffold protein, which acts as a template for capsid assembly as well as a specific encapsulation signal for Cas9. Our results indicate that Cas9 and a single-guide RNA are packaged inside the P22 VLP, and activity assays indicate that this RNA-guided endonuclease is functional for sequence-specific cleavage of dsDNA targets. This work demonstrates the potential for developing P22 as a delivery vehicle for cell specific targeting of Cas9. PMID- 26894838 TI - Interaction of Cu(+) with cytosine and formation of i-motif-like C-M(+)-C complexes: alkali versus coinage metals. AB - The Watson-Crick structure of DNA is among the most well-known molecular structures of our time. However, alternative base-pairing motifs are also known to occur, often depending on base sequence, pH, or the presence of cations. Pairing of cytosine (C) bases induced by the sharing of a single proton (C-H(+) C) may give rise to the so-called i-motif, which occurs primarily in expanded trinucleotide repeats and the telomeric region of DNA, particularly at low pH. At physiological pH, silver cations were recently found to stabilize C dimers in a C Ag(+)-C structure analogous to the hemiprotonated C-dimer. Here we use infrared ion spectroscopy in combination with density functional theory calculations at the B3LYP/6-311G+(2df,2p) level to show that copper in the 1+ oxidation state induces an analogous formation of C-Cu(+)-C structures. In contrast to protons and these transition metal ions, alkali metal ions induce a different dimer structure, where each ligand coordinates the alkali metal ion in a bidentate fashion in which the N3 and O2 atoms of both cytosine ligands coordinate to the metal ion, sacrificing hydrogen-bonding interactions between the ligands for improved chelation of the metal cation. PMID- 26894839 TI - Social Media Use in Patients with Inflammatory Bowel Disease. AB - Patients with chronic illnesses such as Inflammatory Bowel Disease (IBD) have been more keen to utilize the Internet and in particular, social media to obtain patient educational information in recent years. It is important for the gastroenterologist to be aware of these modalities and how they might affect information exchange and ultimately, disease management. This article addresses the current prevalence of social media use, advent of mobile health applications, social media usage in patients with chronic conditions, usage amongst providers, and most notably, the usage and preferences in IBD patients. Over the last decade there has been an increasing desire from patients to receive educational material about their disease through social media. We reviewed the medical literature on the quality of IBD-related information on social media. Given the disparity of information available on the Internet, we remark on the quality of this information and stress the need for further research to assess the validity of IBD information posted on social media. PMID- 26894840 TI - Micro-scale finite element modeling of ultrasound propagation in aluminum trabecular bone-mimicking phantoms: A comparison between numerical simulation and experimental results. AB - The present study investigated the accuracy of micro-scale finite element modeling for simulating broadband ultrasound propagation in water-saturated trabecular bone-mimicking phantoms. To this end, five commercially manufactured aluminum foam samples as trabecular bone-mimicking phantoms were utilized for ultrasonic immersion through-transmission experiments. Based on micro-computed tomography images of the same physical samples, three-dimensional high-resolution computational samples were generated to be implemented in the micro-scale finite element models. The finite element models employed the standard Galerkin finite element method (FEM) in time domain to simulate the ultrasonic experiments. The numerical simulations did not include energy dissipative mechanisms of ultrasonic attenuation; however, they expectedly simulated reflection, refraction, scattering, and wave mode conversion. The accuracy of the finite element simulations were evaluated by comparing the simulated ultrasonic attenuation and velocity with the experimental data. The maximum and the average relative errors between the experimental and simulated attenuation coefficients in the frequency range of 0.6-1.4 MHz were 17% and 6% respectively. Moreover, the simulations closely predicted the time-of-flight based velocities and the phase velocities of ultrasound with maximum relative errors of 20 m/s and 11 m/s respectively. The results of this study strongly suggest that micro-scale finite element modeling can effectively simulate broadband ultrasound propagation in water-saturated trabecular bone-mimicking structures. PMID- 26894841 TI - 3,3'-OH curcumin causes apoptosis in HepG2 cells through ROS-mediated pathway. AB - In this paper, we synthesized a series of curcumin analogs and evaluated their cytotoxicity against HepG2 cells. The results exhibited that the hydroxyl group at 3,3'-position play an essential role in enhancing their anti-proliferation activity. More importantly, 3,3'-hydroxy curcumin (1b) caused apoptosis in HepG2 cells with the ROS generation, which may be mainly composed of hydroxyl radicals (HO) and H2O2. The more cytotoxic activity and ROS-generating ability of 1b may be due to the more stable in (RPMI)-1640 medium and more massive uptake than curcumin. Then the generation of ROS can disrupt the intracellular redox balance, induce lipid peroxidation, cause the collapse of the mitochondrial membrane potential and ultimately lead to apoptosis. The results not only suggest that 3,3'-hydroxy curcumin (1b) may cause HepG2 cells apoptosis through ROS-mediated pathway, but also offer an important information for design of curcumin analog. PMID- 26894842 TI - UiO-67-type Metal-Organic Frameworks with Enhanced Water Stability and Methane Adsorption Capacity. AB - The structure and properties of two new UiO-67-type metal-organic frameworks, along with their linker synthesis and powder and single crystal synthesis, are presented. The new MOFs, UiO-67-Me and UiO-67-BN, are based on 3,3' dimethylbiphenyl and 1,1'-binaphthyl linker scaffolds, and show a much higher stability to water than the thoroughly investigated UiO-67, which is based on the biphenyl scaffold. On the basis of structure models obtained from single crystal X-ray diffraction, it is seen that these linkers are partly shielding the Zr cluster. The new materials have higher density than UiO-67, but show a higher volumetric adsorption capacity for methane. UiO-67-BN exhibits excellent reversible water sorption properties, and enhanced stability to aqueous solutions over a wide pH range; it is to the best of our knowledge the most stable Zr-MOF that is isostructural to UiO-67 in aqueous solutions. PMID- 26894843 TI - Detection and identification of dyes in blue writing inks by LC-DAD-orbitrap MS. AB - In the field of forensic questioned document examination, to identify dyes detected in inks not only provides a solid foundation for ink discrimination in forged contents identification, but also facilitates the investigation of ink origin or the study regarding ink dating. To detect and identify potential acid and basic dyes in blue writing inks, a liquid chromatography-diode array detection-Orbitrap mass spectrometry (LC-DAD-Orbitrap MS) method was established. Three sulfonic acid dyes (Acid blue 1, Acid blue 9 and Acid red 52) and six triphenylmethane basic dyes (Ethyl violet, Crystal violet, Methyl violet 2B, Basic blue 7, Victoria blue B and Victoria blue R) were employed as reference dyes for method development. Determination of the nine dyes was validated to evaluate the instrument performance, and it turned out to be sensitive and stable enough for quantification. The method was then applied in the screening analysis of ten blue roller ball pen inks and twenty blue ballpoint pen inks. As a result, including TPR (a de-methylated product of Crystal violet), ten known dyes and four unknown dyes were detected in the inks. The latter were further identified as a de-methylated product of Victoria blue B, Acid blue 104, Acid violet 49 and Acid blue 90, through analyzing their characteristic precursor and product ions acquired by Orbitrap MS with good mass accuracy. The results showed that the established method is capable of detecting and identifying potential dyes in blue writing inks. PMID- 26894844 TI - Ab initio lattice dynamics and thermochemistry of layered bismuth telluride (Bi2Te3). AB - We present density-functional theory calculations of the lattice dynamics of bismuth telluride, yielding force constants, mean-square displacements and partial densities of phonon states which corroborate and complement previous nuclear inelastic scattering experiments. From these data, we derive an element- and energy-resolved view of the vibrational anharmonicity, quantified by the macroscopic Gruneisen parameter gamma which results in 1.56. Finally, we calculate thermochemical properties in the quasiharmonic approximation, especially the heat capacity at constant pressure and the enthalpy of formation for bismuth telluride; the latter arrives at DeltaHf (Bi2Te3) = -102 kJ mol(-1) at 298 K. PMID- 26894846 TI - Green synthesis, characterization, photocatalytic, fluorescence and antimicrobial activities of Cochlospermum gossypium capped Ag2S nanoparticles. AB - The study describes a simple and green method for the synthesis of silver sulfide nanoparticles (Ag2S NPs) using gum kondagogu (Cochlospermum gossypium) (GK). The synthesized NPs were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), X ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), fluorescence, UV-vis absorption, zeta potential and thermogravimetric analysis (TGA) techniques. The optical properties and quantum confinement effect of the products were confirmed by means of spectroscopic measurements. The morphologies and sizes were characterized by SEM and TEM. The Ag2S NPs were spherical in shape with an effective diameter size of 25 nm. The photocatalytic property of Ag2S NPs was evaluated by the degradation of fluorescein (FL) dye under solar light. The effect of Ag2SNPs on the photocatalytic degradation of FL dye and influence of other parameters such as Ag2S loading, H2O2, temperature and under solar light irradiation was also evaluated. The degradation reaction follows the pseudo-first order kinetics. The apparent reaction rate was used to calculate the apparent activation energy (Ea=13.95 kJ/mol) of the degradation process. The activation thermodynamic parameters (DeltaG*, DeltaH* and DeltaS*) were obtained from variable temperature kinetic studies. The interaction between Ag2S NPs and bovine serum albumin (BSA) was studied by using fluorescence spectroscopic measurements. The synthesized Ag2S NPs were showing good antimicrobial activity. PMID- 26894845 TI - Impact of an Energy Drink on the Structure of Stomach and Pancreas of Albino Rat: Can Omega-3 Provide a Protection? AB - BACKGROUND AND OBJECTIVES: A controversy developed between the benefits of energy drinks (EDs) versus the possible health threats since its revolution. Lack of information was a call to assess the effect of chronic consumption of Power Horse (PH) as one of the EDs, on the structure of pancreas and fundic mucosa of stomach in rats, and possible protective role of Omega-3. MATERIALS AND METHODS: Thirty two adult male albino rats were divided equally into 4 groups; control received group which only received a standard diet, Omega-3 group, PH group which given PH and PH plus Omega-3 group received both PH plus Omega-3 for 4 weeks. Biochemical assessment of blood glucose, serum insulin, gastrin, tumor necrosis factor alpha (TNF-alpha) and inducible nitric oxide synthetase (iNOS) was performed. The antioxidant activity and histopathological examination of both pancreatic tissue and fundic mucosa of stomach were assessed. RESULTS: Administration of PH significantly increased serum insulin and glucose levels while it significantly reduced serum gastrin level compared to control. PH also caused oxidants/antioxidants imbalance in both pancreas and fundic mucosa. The latter revealed degenerative changes and increased apoptosis which was evident by increased caspase-3 immunoexpression. Pancreas exhibited signs of beta-cells overstimulation. Fundic mucosa showed reduced number of parietal cells, gastrin hormone expression compared to control group. Omega-3 administration could alleviate, to some extent, these changes. It significantly decreased TNF-alpha, iNOS and reduced glutathione (GSH) as well as significantly increasing superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities compared to the group which received PH alone. CONCLUSION: Power Horse intake significantly injures islet cells, pancreatic acini as well as the glandular cells of the fundic mucosa. Omega-3 decreases these detrimental effects mostly through its antioxidant and anti-inflammatory action. PMID- 26894847 TI - Interplay of multiple interaction forces: Binding of tyrosine kinase inhibitor nintedanib with human serum albumin. AB - In this study, we have investigated the binding affinity of the newly approved tyrosine kinase inhibitor nintedanib (NIB) with human serum albumin under simulated physiological condition. The obtained results demonstrate that fluorescence intensity of human serum albumin (HSA) gets quenched by NIB and quenching occurs in static manner. Binding parameters calculated from modified Stern-Volmer equation shows that the drug binds to human serum albumin with a binding constant in the order of 10(3), with the number of binding sites approximately equal to one. Synchronous fluorescence data deciphered the change in the microenvironment of tryptophan (Trp) residue in HSA. Circular dichroism data showed an increase in helical content upon drug binding. Dynamic light scattering measurements deciphered the reduction in hydrodynamic radii of the protein, further differential scanning calorimetry results shows that nintedanib increase the thermostability of HSA. Molecular docking results demonstrated that major binding forces involved in the complex formation are hydrogen bonding and hydrophobic interaction. PMID- 26894848 TI - Exploring the photochemosensitivity by novel cysteine-based mixed ligand complexes. AB - A new series of cysteine-based metal(II) complexes with 2,2'-bipyridine or 1,10 phenanthroline as co-ligand have been prepared and characterized. Their DNA binding and cleavage properties have been studied. The analytical and spectroscopic data of complexes 1-18 reveal that the complexes adopt an octahedral geometry around the central metal ion in which the cysteine is coordinated through NS and NN atoms, respectively. Spectroscopic titration and viscosity measurements reveal that the complexes bind to DNA through an intercalative mode. Electrophoresis measurements exhibit that they cleave pBR322 DNA efficiently in the presence of 3-mercaptopropionic acid (MPA), probably via hydrolytic mechanism with the involvement of (*)OH. The in vitro anticancer activities indicate that the Cu(II) complexes are active against four selected human tumor cell lines. Furthermore, it is remarkable that all the complexes exhibit significant photocytotoxicity against human breast cancer cell lines (MCF 7) with a potency more than the widely used drugs photofrin and cisplatin indicating that they have the potential to act as effective anticancer drugs in a dose-dependent manner. PMID- 26894850 TI - A multi-residue method for simultaneous determination of 74 pesticides in Chinese material medica using modified QuEChERS sample preparation procedure and gas chromatography tandem mass spectrometry. AB - The present study is focused on the development of an analytical method for the simultaneous analysis of seventy-four pesticides belonging to different chemical classes (organochlorines, organophosphates, pyrethroids, dinitroanilines, dicarboximides, triazoles, etc.) in Chinese material medica. The samples were extracted according to the acetate QuEChERS protocol. To reduce the amount of co extracted compounds, n-hexane instead of acetonitrile was employed as the extraction solvent. To improve the overall recoveries of problematic basic and base-sensitive compounds, sodium acetate was used to adjust the pH to a neutral condition, and florisil combined with octadecyl-modified silica (C18) were utilized in the cleanup step. The samples were analysed by GC-MS/MS, and quantified by matrix-matched calibration. The validation study was carried out on two representative herbs, Chuanxiong Rhizoma and Angelica Sinensis Radix. In two matrices, the linearity of the calibration was good between 5 and 250 ng/mL concentration ranges, and the limits of quantification (LOQs) less than 0.01 mg/kg for most pesticides. At the LOQs and ten times the LOQs, the mean recoveries of almost all pesticides were within 70-120%, with relative standard deviations (RSDs) lower than 10%. The method was applied on twenty real samples. Seven batches of Chuanxiong and five batches of Danggui were found to contain the residues. The combination of modified QuEChERS and GC-MS/MS offers low cost of analysis as well as excellent accuracy and sensitivity. This method could be especially useful for trace analysis of pesticide residues in complex matrices. PMID- 26894851 TI - Enantioseparation and determination of isofenphos-methyl enantiomers in wheat, corn, peanut and soil with Supercritical fluid chromatography/tandem mass spectrometric method. AB - Supercritical fluid chromatography/tandem mass spectrometry (SFC-MS/MS) is an effective tool in separation science which uses the nontoxic CO2 fluid for better control of analyte retention. Also the technology of a postcolumn additive to complement MS/MS ensure the high-selectivity determination. In this paper, a green and sensitive analytical method was developed for the enantioselective separation and determination of isofenphos-methyl enantiomers in foodstuff and soil by SFC-MS/MS. The enantioseparation was performed within 3.50 min using Chiralpak IA-3 column with CO2/isopropanol (90:10, v/v) as the mobile phase at 2.2 mL/min flow rate. The postcolumn compensation technology provided with 0.1% formic acid/methanol greatly improved the ionization efficiency of mass spectrometry. Column temperature, auto back pressure regulator pressure, and flow rate of compensation solvent were optimized to 30 degrees C, 2200 psi, and 0.1 mL/min, respectively. The QuEChERs method was adopted in this study, which mean recoveries of isofenphos-methyl enantiomers ranged from 75.7% to 111.4%, with relative standard deviations less than 11.3% at three concentration levels in all matrices. The limits of detection for both enantiomers varied from 0.02 MUg/kg to 0.15 MUg/kg, while the limit of quantification did not exceed 0.50 MUg/kg. The proposed method was then successfully applied to analyze authentic samples, confirming that it was a versatile strategy for the analysis of isofenphos-methyl enantiomers in food and environmental matrices. PMID- 26894849 TI - Ultraviolet blood irradiation: Is it time to remember "the cure that time forgot"? AB - Ultraviolet blood irradiation (UBI) was extensively used in the 1940s and 1950s to treat many diseases including septicemia, pneumonia, tuberculosis, arthritis, asthma, and even poliomyelitis. The early studies were carried out by several physicians in USA and published in the American Journal of Surgery. However, with the development of antibiotics, the use of UBI declined and it has now been called "the cure that time forgot." Later studies were mostly performed by Russian workers, and in other Eastern countries, and the modern view in Western countries is that UBI remains highly controversial. This review discusses the potential of UBI as an alternative approach to current methods used to treat infections, as an immune-modulating therapy and as a method for normalizing blood parameters. Low and mild doses of UV kill microorganisms by damaging the DNA, while any DNA damage in host cells can be rapidly repaired by DNA repair enzymes. However, the use of UBI to treat septicemia cannot be solely due to UV-mediated killing of bacteria in the bloodstream, as only 5-7% of blood volume needs to be treated with UV to produce the optimum benefit, and higher doses can be damaging. There may be some similarities to extracorporeal photopheresis (ECP) using psoralens and UVA irradiation. However, there are differences between UBI and ECP in that UBI tends to stimulate the immune system, while ECP tends to be immunosuppressive. With the recent emergence of bacteria that are resistant to all known antibiotics, UBI should be more investigated as an alternative approach to infections, and as an immune-modulating therapy. PMID- 26894703 TI - Measurement of the Top Quark Pair Production Cross Section in Proton-Proton Collisions at ?[s]=13 TeV. AB - The top quark pair production cross section is measured for the first time in proton-proton collisions at sqrt[s]=13 TeV by the CMS experiment at the CERN LHC, using data corresponding to an integrated luminosity of 43 pb^{-1}. The measurement is performed by analyzing events with at least one electron and one muon of opposite charge, and at least two jets. The measured cross section is 746+/-58(stat)+/-53(syst)+/-36(lumi) pb, in agreement with the expectation from the standard model. PMID- 26894852 TI - Bioprospecting of microalgae: Proper extraction followed by high performance liquid chromatographic-high resolution mass spectrometric fingerprinting as key tools for successful metabolom characterization. AB - Currently, the interest in microalgae as a source of biologically active components exploitable as supplementary ingredients to food/feed or in cosmetics continues to increase. Existing research mainly aims to focus on revealing and recovering the rare, cost competitive components of the algae metabolom. Because these components could be of very different physicochemical character, a universal approach for their isolation and characterization should be developed. This study demonstrates the systematic development of the extraction strategy that represents one of the key challenges in effective algae bioprospecting, which predefines their further industrial application. By using of Trachydiscus minutus as a model microalgae biomass, following procedures were tested and critically evaluated in order to develop the generic procedure for microalgae bioprospecting: (i) various ways of mechanical disintegration of algae cells enabling maximum extraction efficiency, (ii) the use of a wide range of extraction solvents/solvent mixtures suitable for optimal extraction yields of polar, medium-polar, and non-polar compounds, (iii) the use of consecutive extractions as a fractionation approach. Within the study, targeted screening of selected compounds representing broad range of polarities was realized by ultra high performance liquid chromatography coupled with high resolution tandem mass spectrometric detection (UHPLC-HRMS/MS), to assess the effectiveness of undertaken isolation steps. As a result, simple and high-throughput extraction fractionation strategy based on consecutive extraction with water-aqueous methanol-hexane/isopropanol was developed. Moreover, to demonstrate the potential of the UHPLC-HRMS/MS for the retrospective non-target screening and compounds identification, the collected mass spectra have been evaluated to characterize the pattern of extracted metabolites. Attention was focused on medium-/non-polar extracts and characterization of lipid species present in the T. minutus algae. Such detailed information on the composition of native (non-hydrolyzed) lipids of this microalga has not been published yet. PMID- 26894853 TI - Development and validation of an UPLC-MS/MS method for the quantification of irinotecan, SN-38 and SN-38 glucuronide in plasma, urine, feces, liver and kidney: Application to a pharmacokinetic study of irinotecan in rats. AB - The objective of this research is to develop and validate a sensitive and reproducible UPLC-MS/MS method to quantify irinotecan, its active metabolite SN 38 and SN-38 glucuronide (phase II metabolite of SN-38) simultaneously in different bio-matrices (plasma, urine, feces), tissues (liver and kidney) and to use the method to investigate its pharmacokinetic behavior in rats. Irinotecan, SN-38 and SN-38 glucuronide has been resolved and separated by C18 column using acetonitrile and 0.1% formic acid in water used as the mobile phases. Triple quadruple mass spectrometer using multiple reaction monitoring (MRM) with positive scan mode were employed to perform mass analysis. The results showed that the linear response range of irinotecan and SN-38 in plasma, feces, liver and kidney is 4.88-10000 nM, 39-5000 nM, 48.8-6250 nM and 48.8-6250 nM, respectively (R(2)>0.99). In case of SN-38 glucuronide, the standard curves were linear in the concentration range of 6.25-2000 nM, 4.88-1250 nM, 9.8-1250 nM and 9.8-1250 nM in plasma, feces, liver and kidney homogenates, respectively. The lower limit of detection (LLOD) of irinotecan, SN-38 and SN-38 glucuronide was determined to be less than 25 nM in all bio-matrices as well as tissue homogenates. Recoveries of irinotecan, SN-38 and SN-38 glucuronide at three different concentrations (low, medium and high) were not less than 85% at three different concentrations in plasma and feces. The percentage matrix factors in different bio-matrices and tissues were within 20%. The UPLC-MS/MS method was validated with intra-day and inter-day precision of less than 15% in plasma, feces, liver and kidney. Owing to the high sensitivity of this method, only 20 MUl of plasma, urine and homogenates of liver, kidney and feces is needed. The validated method has been successfully employed for pharmacokinetic evaluation of irinotecan in male wistar rats to quantify irinotecan, SN-38 and SN-38 glucuronide in plasma, feces, and urine samples. PMID- 26894856 TI - Ubiquitin ligase UBE3C promotes melanoma progression by increasing epithelial mesenchymal transition in melanoma cells. AB - Melanoma is the most aggressive type of skin cancer, exhibiting extensive local invasion and early distant metastasis. Aberrant expression of ubiquitin-protein ligase E3C (UBE3C) plays a key role in tumor development and progression. In the present study, we analyzed UBE3C expression in samples of cancerous and normal skin tissue. Levels of UBE3C expression were much higher in primary and metastatic melanoma tissues than in normal skin, cutaneous squamous cell carcinoma or basal cell carcinoma. Melanoma cells overexpressing UBE3C frequently exhibited a mesenchymal phenotype, including reduced expression of the epithelial marker E-cadherin and expression of the mesenchymal marker vimentin. Knockdown of UBE3C expression in melanoma cells significantly suppressed melanoma growth and progression. Furthermore, silencing UBE3C led to increased E-cadherin expression and decreased vimentin and Snail1 expression. Thus UBE3C promotes melanoma progression, possibly by inducing epithelial-mesenchymal transition in melanoma cells. Inhibiting UBE3C activity may suppress melanoma invasion and metastasis and may represent a targeted therapeutic approach. PMID- 26894858 TI - Efficacy and safety of sorafenib versus sunitinib as first-line treatment in patients with metastatic renal cell carcinoma: largest single-center retrospective analysis. AB - We conducted this largest, single-center, retrospective study to determine the efficacy of sorafenib versus sunitinib as first-line therapy for metastatic renal cell carcinoma (mRCC) in Chinese patients to validate the potential data on direct comparison of the efficacy of first-line treatment with sorafenib and sunitinib in the treatment of mRCC. From November 2006 to March 2015, we reviewed medical records from Peking University Cancer Hospital and found 169 patients receiving sorafenib (400 mg orally BID continuously in a 4-week cycle) and 165 patients receiving sunitinib (50 mg orally daily in a 6-week cycle; 4/2 schedule) as the first-line targeted therapy. Median follow-up was 23.0 months. In sorafenib and sunitinib groups, there is no significant difference in progression free survival (PFS) (9.0 months [95%CI:8.00-12.00] vs 11.0 months [95%CI:9.00 14.00], respectively; P=0.6289) and overall survival (OS) (28.0 months [95%CI:24.00-34.00] vs 28.0 months [95% CI:19.00-33.00], respectively; P=0.979). Subgroup analysis based on Karnofsky performance status (KPS), pathological type, Memorial Sloan Kettering Cancer Center score, and metastasis was also conducted. Multivariate analysis revealed that sorafenib treated patients had superior efficacy in patients with a KPS of <90 and significantly better PFS (hazard ratio: 0.460 [95% CI:0.222-0.954]). Most common adverse events were hand-foot skin reaction and thrombocytopenia which were manageable. Overall, no significant differences were seen between sorafenib and sunitinib in the treatment of advanced renal cancer. However, fewer toxicities associated with sorafenib and superior efficacy in subgroups (non-clear cell carcinoma and KPS <90) indicates sorafenib as an effective first-line treatment agent in patients with mRCC. PMID- 26894854 TI - Characterization of novel low passage primary and metastatic colorectal cancer cell lines. AB - In vitro models are essential to understanding the molecular characteristics of colorectal cancer (CRC) and the testing of therapies for CRC. Many efforts to establish and characterize primary CRC cell lines have been published, most describing a small number of novel cell lines. However, there remains a lack of a large panel of uniformly established and characterized cell lines. To this end we established 20 novel CRC cell lines, of which six were derived from liver metastases. Genetic, genomic and transcriptomic profiling was performed in order to characterize these new cell lines. All data are made publically available upon publication.By combining mutation profiles with CNA and gene expression profiles, we generated an overall profile of the alterations in the major CRC-related signaling pathways. The combination of mutation profiles with genome, transcriptome and methylome data means that these low passage cell lines are among the best characterized of all CRC cell lines. This will allow researchers to select model cell lines appropriate to specific experiments, facilitating the optimal use of these cell lines as in vitro models for CRC. All cell lines are available for further research. PMID- 26894857 TI - 14-3-3sigma regulation of and interaction with YAP1 in acquired gemcitabine resistance via promoting ribonucleotide reductase expression. AB - Gemcitabine is an important anticancer therapeutics approved for treatment of several human cancers including locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC). Its clinical effectiveness, however, is hindered by existence of intrinsic and development of acquired resistances. Previously, it was found that 14-3-3sigma expression associates with poor clinical outcome of PDAC patients. It was also found that 14-3-3sigma expression is up-regulated in gemcitabine resistant PDAC cells and contributes to the acquired gemcitabine resistance. In this study, we investigated the molecular mechanism of 14-3-3sigma function in gemcitabine resistance and found that 14-3-3sigma up-regulates YAP1 expression and then binds to YAP1 to inhibit gemcitabine-induced caspase 8 activation and apoptosis. 14-3-3sigma association with YAP1 up-regulates the expression of ribonucleotide reductase M1 and M2, which may mediate 14-3 3sigma/YAP1 function in the acquired gemcitabine resistance. These findings suggest a possible role of YAP1 signaling in gemcitabine resistance. PMID- 26894855 TI - Reduction of gastric cancer proliferation and invasion by miR-15a mediated suppression of Bmi-1 translation. AB - B-cell specific moloney leukemia virus insertion site 1 (Bmi-1) gene plays important roles in gastric cancer, but the epigenetic regulatory mechanism by microRNA (miRNA) and the functional significance of Bmi-1 inhibition in gastric cancer remains elusive. In this study, we systematically investigated the functional roles of miRNA mediated Bmi-1 suppression in gastric cancer. Our results show that the expression of miR-15a is significantly reduced in gastric cancer and the protein expression levels of Bmi-1 are inversely correlated with miR-15a (P = 0.034) in gastric cancer patient samples. Functional studies revealed that ectopic expression of miR-15a decreased Bmi-1 in gastric cancer cell lines with reduced proliferation and tumor invasion. High levels of Bmi-1 in gastric cancer patients are significantly associated with better overall survival (P = 0.024) based on the Kaplan-Meier survival analysis. PMID- 26894860 TI - The influence of marital status on the stage at diagnosis, treatment, and survival of adult patients with gastric cancer: a population-based study. AB - BACKGROUND & AIMS: Marital status was reported as a prognostic factor in many cancers. However, its role in gastric cancer (GC) hasn't been thoroughly explored. In this study, we aimed to investigate the effect of marital status on survival, stage, treatment, and survival in subgroups. METHODS: We used the Surveillance, Epidemiology and End Results (SEER) database and identified 16910 GC patients. These patients were categorized into married (58.44%) and unmarred (41.56%) groups. Pearson chi-square, Wilcoxon-Mann-Whitney, Log-rank, multivariate Cox regression, univariate and multivariate binomial or multinomial logistic regression analysis were used in our analysis. Subgroup analyses of married versus unmarried patients were summarized in a forest plot. RESULTS: Married patients had better 5-year overall survival (OS) (32.09% VS 24.61%, P<0.001) and 5-year cancer-caused special survival (CSS) (37.74% VS 32.79%, P<0.001) than unmarried ones. Then we studied several underlying mechanisms. Firstly, married patients weren't in earlier stage at diagnosis (P=0.159). Secondly, married patients were more likely to receive surgery (P < 0.001) or radiotherapy (P < 0.001) compared with the unmarried. Thirdly, in subgroup analyses, married patients still had survival advantage in subgroups with stage II-IV and no radiotherapy. CONCLUSIONS: These results showed that marital status was an independently prognostic factor for both OS and CSS in GC patients. Undertreatment and lack of social support in unmarried patients were potential explanations. With the knowledge of heterogeneous effects of marriage in subgroups, we can target unmarried patients with better social support, especially who are diagnosed at late stage and undergo no treatment. PMID- 26894859 TI - Transcriptomic analysis of aggressive meningiomas identifies PTTG1 and LEPR as prognostic biomarkers independent of WHO grade. AB - Meningiomas are frequent central nervous system tumors. Although most meningiomas are benign (WHO grade I) and curable by surgery, WHO grade II and III tumors remain therapeutically challenging due to frequent recurrence. Interestingly, relapse also occurs in some WHO grade I meningiomas. Hence, we investigated the transcriptional features defining aggressive (recurrent, malignantly progressing or WHO grade III) meningiomas in 144 cases. Meningiomas were categorized into non recurrent (NR), recurrent (R), and tumors undergoing malignant progression (M) in addition to their WHO grade. Unsupervised transcriptomic analysis in 62 meningiomas revealed transcriptional profiles lining up according to WHO grade and clinical subgroup. Notably aggressive subgroups (R+M tumors and WHO grade III) shared a large set of differentially expressed genes (n=332; p<0.01, FC>1.25). In an independent multicenter validation set (n=82), differential expression of 10 genes between WHO grades was confirmed. Additionally, among WHO grade I tumors differential expression between NR and aggressive R+M tumors was affirmed for PTTG1, AURKB, ECT2, UBE2C and PRC1, while MN1 and LEPR discriminated between NR and R+M WHO grade II tumors. Univariate survival analysis revealed a significant association with progression-free survival for PTTG1, LEPR, MN1, ECT2, PRC1, COX10, UBE2C expression, while multivariate analysis identified a prediction for PTTG1 and LEPR mRNA expression independent of gender, WHO grade and extent of resection. Finally, stainings of PTTG1 and LEPR confirmed malignancy-associated protein expression changes. In conclusion, based on the so far largest study sample of WHO grade III and recurrent meningiomas we report a comprehensive transcriptional landscape and two prognostic markers. PMID- 26894862 TI - HULC long noncoding RNA silencing suppresses angiogenesis by regulating ESM-1 via the PI3K/Akt/mTOR signaling pathway in human gliomas. AB - Tumor angiogenesis plays a critical role in the tumor progression. Highly upregulated in liver cancer (HULC) is a long noncoding RNA (lncRNA) that acts as an oncogene in gliomas. We found that HULC, vascular endothelial growth factor (VEGF), and ESM-1 (endothelial cell specific molecule 1) expression and microvessel density were positively correlated with grade dependency in glioma patient tissues, and that HULC silencing suppressed angiogenesis by inhibiting glioma cells proliferation and invasion. This process induced anoikis and blocked the cell cycle at G1/S phase via the PI3K/Akt/mTOR signaling pathway, thus regulating the tumor-related genes involved in the above biological behavior in human glioma U87MG and U251 cells. However, these effects were reversed by ESM-1 overexpression, suggesting a mediating role of ESM-1 in the pro-angiogenesis effect of HULC. Our results define the mechanism of the pro-angiogenesis activity of HULC, which shows potential for application as a therapeutic target in glioma. PMID- 26894865 TI - Risk mitigation in academic drug discovery. PMID- 26894861 TI - Cell-surface markers for colon adenoma and adenocarcinoma. AB - Early detection of colorectal cancer (CRC) is crucial for effective treatment. Among CRC screening techniques, optical colonoscopy is widely considered the gold standard. However, it is a costly and invasive procedure with a low rate of compliance. Our long-term goal is to develop molecular imaging agents for the non invasive detection of CRC by molecular imaging-based colonoscopy using CT, MRI or fluorescence. To achieve this, cell surface targets must be identified and validated. Here, we report the discovery of cell-surface markers that distinguish CRC from surrounding tissues that could be used as molecular imaging targets. Profiling of mRNA expression microarray data from patient tissues including adenoma, adenocarcinoma, and normal gastrointestinal tissues was used to identify potential CRC specific cell-surface markers. Of the identified markers, six were selected for further validation (CLDN1, GPR56, GRM8, LY6G6D/F, SLCO1B3 and TLR4). Protein expression was confirmed by immunohistochemistry of patient tissues. Except for SLCO1B3, diffuse and low expression was observed for each marker in normal colon tissues. The three markers with the greatest protein overexpression were CLDN1, LY6G6D/F and TLR4, where at least one of these markers was overexpressed in 97% of the CRC samples. GPR56, LY6G6D/F and SLCO1B3 protein expression was significantly correlated with the proximal tumor location and with expression of mismatch repair genes. Marker expression was further validated in CRC cell lines. Hence, three cell-surface markers were discovered that distinguish CRC from surrounding normal tissues. These markers can be used to develop imaging or therapeutic agents targeted to the luminal surface of CRC. PMID- 26894864 TI - The SOX11 transcription factor is a critical regulator of basal-like breast cancer growth, invasion, and basal-like gene expression. AB - Basal-like breast cancers (BLBCs) are aggressive breast cancers associated with poor survival. Defining the key drivers of BLBC growth will allow identification of molecules for targeted therapy. In this study, we performed a primary screen integrating multiple assays that compare transcription factor expression and activity in BLBC and non-BLBC at the RNA, DNA, and protein levels. This integrated screen identified 33 transcription factors that were elevated in BLBC in multiple assays comparing mRNA expression, DNA cis-element sequences, or protein DNA-binding activity. In a secondary screen to identify transcription factors critical for BLBC cell growth, 8 of the 33 candidate transcription factors (TFs) were found to be necessary for growth in at least two of three BLBC cell lines. Of these 8 transcription factors, SOX11 was the only transcription factor required for BLBC growth, but not for growth of non-BLBC cells. Our studies demonstrate that SOX11 is a critical regulator of multiple BLBC phenotypes, including growth, migration, invasion, and expression of signature BLBC genes. High SOX11 expression was also found to be an independent prognostic indicator of poor survival in women with breast cancer. These results identify SOX11 as a potential target for the treatment of BLBC, the most aggressive form of breast cancer. PMID- 26894866 TI - Ferroelectrically Gated Atomically Thin Transition-Metal Dichalcogenides as Nonvolatile Memory. AB - Ferroelectrically driven nonvolatile memory is demonstrated by interfacing 2D semiconductors and ferroelectric thin films, exhibiting superior memory performance comparable to existing thin-film ferroelectric field-effect transistors. An optical memory effect is also observed with large modulation of photoluminescence tuned by the ferroelectric gating, potentially finding applications in optoelectronics and valleytronics. PMID- 26894863 TI - A new immunohistochemistry prognostic score (IPS) for recurrence and survival in resected pancreatic neuroendocrine tumors (PanNET). AB - Pancreatic neuroendocrine tumor (PanNET) is a neoplastic entity in which few prognostic factors are well-known. Here, we aimed to evaluate the prognostic significance of N-myc downstream-regulated gen-1 (NDRG-1), O6-methylguanine DNA methyltransferase (MGMT) and Pleckstrin homology-like domain family A member 3 (PHLDA-3) by immunohistochemistry (IHC) and methylation analysis in 92 patients with resected PanNET and follow-up longer than 24 months. In multivariate analyses, ki-67 and our immunohistochemistry prognostic score (IPS-based on MGMT, NDRG-1 and PHLDA-3 IHC expression) were independent prognostic factors for disease-free-survival (DFS), while age and IPS were independent prognostic factors for overall survival (OS). Our IPS could be a useful prognostic biomarker for recurrence and survival in patients following resection for PanNET. PMID- 26894867 TI - [Early Diagnosis of Osteoarthritis: Clinical Reality and Promising Experimental Techniques]. AB - It is considered that the structural damage in early osteoarthritis (OA) is potentially reversible. It is therefore particularly important for orthopaedic and trauma surgery to develop strategies and technologies for diagnosing early OA processes. This review presents 3 case reports to illustrate the current clinical diagnostic procedure for OA. Experimental techniques with translational character are discussed in the context of the detection of early degenerative processes relevant to OA. Non-invasive imaging methods such as quantitative MRI, ultrasound, optical coherence tomography (OCT), scintigraphy and diffraction enhanced synchrotron imaging (DEI), as well as biochemical methods and proteomics, are considered. Early detection of OA is reviewed with minimally invasive techniques, such as arthroscopy, as well as the combination of arthroscopic techniques with indentation, spectrometry, and multiphoton microscopy. In addition, a brief summary of macroscopic and histologic scores is presented. Finally, the spatial organisation of joint surface chondrocytes as an image-based biomarker is used to illustrate an early OA detection strategy that focusses on early changes in tissue architecture potentially prior to damage. In summary, multiple translational techniques are able to detect early OA processes but we do not know whether they truly represent the initial events. Moreover, at this point it is difficult to judge the future clinical relevance of these procedures and to compare their efficacy, as there have been comparative studies. However, the expected gain in knowledge will hopefully help us top attain a more comprehensive understanding of early OA and to develop novel methods for its early diagnosis, therapy, and prevention. Overall, the clinical diagnosis of early OA remains one of the greatest challenges of our field. We still face uncharted territory. PMID- 26894868 TI - Cervical Spinal Injury In Pediatric Blunt Trauma Patients: Management In The Emergency Department. AB - Spinal injuries from blunt trauma are uncommon in pediatric patients, representing only about 1.5% of all blunt trauma patients. However, the potentially fatal consequences of spinal injuries make them of great concern to emergency clinicians. Clinical goals in the emergency department are to identify all injuries using selective imaging and to minimize further harm from spinal cord injury. Achieving these goals requires an understanding of the age-related physiologic differences that affect patterns of injury and radiologic interpretation in children, as well as an appreciation of high-risk clinical clues and mechanisms. This issue reviews current approaches to prehospital immobilization, identification of low-risk patients who may be clinically cleared from immobilization, a rational approach to the use of radiologic imaging, and the existing evidence for medical management of spinal cord injuries. PMID- 26894869 TI - Suggestions for Adapting Yoga to the Needs of Older Adults with Osteoporosis. AB - BACKGROUND: Exercise such as yoga may have health benefits for older adults with osteoporosis, but without attention to safe movement yoga can also increase the risk for injury. OBJECTIVE: The current article provides suggestions for how to adapt yoga to the needs of older adults with osteoporosis. SUGGESTIONS: A general guidelines for exercise is that older adults with osteoporosis should participate in a multicomponent exercise program, including resistance and balance training. Contraindicated movements include end-range flexion/extension/rotation of the spine and internal/external rotation of the hip. Yoga postures that should be encouraged include postures emphasizing spinal alignment and extension to mid range in standing and on the floor. Overarching considerations for participation in yoga are that classes should be designed for higher-risk older adults, led by an instructor who has had proper training with individuals with osteoporosis, should be a noncompetitive environment, and should give attention to which postures are safe and how to transition safely. PMID- 26894871 TI - Uptake and degradation of Orange II by zinc aluminum layered double oxides. AB - In this work ZnAl-layered double oxide composites (LDO) were developed to remove organic dyes in wastewater by adsorption and photocatalysis. Various LDO composites were synthesized by adjusting synthetic parameters including the molar ratio of Zn to Al, and calcination temperature. LDO adsorption and photocatalytic properties for decomposition of organic dyes were also investigated. Orange II sodium salt (OrgII), an azo dye and water contaminant, was chosen as the model to investigate the properties of LDOs compared with commercial ZnO, TiO2 (P25) and ZnO-LDH. The adsorption and photocatalytic performance results showed that LDO composites significantly enhanced adsorption-photocatalytic performance for OrgII degradation. LDO at the Zn/Al molar ratio of 2 (2)LDO has the best adsorption capacity (800.8 mg/g of OrgII for (2)LDO), and improved photocatalytic activity (74.3% of OrgII decomposition for (2)LDO). It is believed that the better adsorption properties of LDO are due to the adsorption and intercalation of dyes in the interlayer during LDO's rehydration process. ZnO/ZnAl-rehydrated layered double hydroxide composites (ZnO-rLDH) after rehydration of LDOs in aqueous solution was also obtained. After restoration in water, the structure and morphology of ZnO-rLDHs were characterized by XRD, FTIR, SEM/TEM, N2 adsorption/desorption and UV-vis-DRS. Finally, the relations between the structural features of the ZnO-rLDH composites and the adsorption properties and photocatalytic activity of LDO was studied. PMID- 26894872 TI - A bismuth based layer structured organic-inorganic hybrid material with enhanced photocatalytic activity. AB - A bismuth-based organic-inorganic hybrid material with layered structure (BiO BTCIE) was synthesized by taking advantage of an ion exchange reaction. The structure of BiO-BTCIE was examined by XRD, EXAFS, FT-IR, TG/DTA, etc. By replacing the HCOO(-) with BTC anions in the Bi2O2(2+) interlayer, the Bi2O2(2+) layer is distorted as revealed by the EXAFS, which lead to a longer life time of the photogenerated charge carriers and a higher photocatalytic activity of BiO BTCIE (more than 10 times). PMID- 26894870 TI - Viral-mimicking protein nanoparticle vaccine for eliciting anti-tumor responses. AB - The immune system is a powerful resource for the eradication of cancer, but to overcome the low immunogenicity of tumor cells, a sufficiently strong CD8(+) T cell-mediated adaptive immune response is required. Nanoparticulate biomaterials represent a potentially effective delivery system for cancer vaccines, as they can be designed to mimic viruses, which are potent inducers of cellular immunity. We have been exploring the non-viral pyruvate dehydrogenase E2 protein nanoparticle as a biomimetic platform for cancer vaccine delivery. Simultaneous conjugation of a melanoma-associated gp100 epitope and CpG to the E2 nanoparticle (CpG-gp-E2) yielded an antigen-specific increase in the CD8(+) T cell proliferation index and IFN-gamma secretion by 1.5-fold and 5-fold, respectively, compared to an unbound peptide and CpG formulation. Remarkably, a single nanoparticle immunization resulted in a 120-fold increase in the frequency of melanoma epitope-specific CD8(+) T cells in draining lymph nodes and a 30-fold increase in the spleen, relative to free peptide with free CpG. Furthermore, in the very aggressive B16 melanoma murine tumor model, prophylactic immunization with CpG-gp-E2 delayed the onset of tumor growth by approximately 5.5 days and increased animal survival time by approximately 40%, compared to PBS-treated animals. These results show that by combining optimal particle size and simultaneous co-delivery of molecular vaccine components, antigen-specific anti tumor immune responses can be significantly increased. PMID- 26894874 TI - Modification of Sodium Release Using Porous Corn Starch and Lipoproteic Matrix. AB - Excessive sodium consumption can result in hypertension, diabetes, heart diseases, stroke, and kidney diseases. Various chips and extruded snacks, where salt is mainly applied on the product surface, accounted for almost 56% of snacks retail sales in 2010. Hence, it is important to target sodium reduction for those snack products. Past studies had shown that modifying the rate-release mechanism of sodium is a promising strategy for sodium reduction in the food industry. Encapsulation of salt can be a possible technique to control sodium release rate. Porous corn starch (PCS), created by enzymatic treatment and spray drying and lipoproteic matrix, created by gelation and freeze drying, were evaluated as carriers for controlled sodium release targeting topically applied salts. Both carriers encapsulated salt and their in vitro sodium release profiles were measured using a conductivity meter. The sodium release profiles of PCS treated with different enzymatic reaction times were not significantly different. Protein content and fat content altered sodium release profile from the lipoproteic matrix. The SEM images of PCS showed that most of the salt crystals coated the starch instead of being encapsulated in the pores while the SEM images and computed tomography scan of lipoproteic matrix showed salt dispersed throughout the matrix. Hence, PCS was found to have limitations as a sodium carrier as it could not effectively encapsulate salt inside its pores. The lipoproteic matrix was found to have a potential as a sodium carrier as it could effectively encapsulate salt and modify the sodium release profile. PMID- 26894873 TI - Effects of Secondary Metabolites from the Fungus Septofusidium berolinense on DNA Cleavage Mediated by Human Topoisomerase IIalpha. AB - Two metabolites from the ascomycete fungus Septofusidium berolinense were recently identified as having antineoplastic activity [Ekiz et al. (2015) J. Antibiot. , DOI: 10.1038/ja.2015.84]. However, the basis for this activity is not known. One of the compounds [3,6-dihydroxy-2-propylbenzaldehyde (GE-1)] is a hydroquinone, and the other [2-hydroxymethyl-3-propylcyclohexa-2,5-diene-1,4 dione (GE-2)] is a quinone. Because some hydroquinones and quinones act as topoisomerase II poisons, the effects of GE-1 and GE-2 on DNA cleavage mediated by human topoisomerase IIalpha were assessed. GE-2 enhanced DNA cleavage ~4-fold and induced scission with a site specificity similar to that of the anticancer drug etoposide. Similar to other quinone-based topoisomerase II poisons, GE-2 displayed several hallmark characteristics of covalent topoisomerase II poisons, including (1) the inability to poison a topoisomerase IIalpha construct that lacks the N-terminal domain, (2) the inhibition of DNA cleavage when the compound was incubated with the enzyme prior to the addition of plasmid, and (3) the loss of poisoning activity in the presence of a reducing agent. In contrast to GE-2, GE-1 did not enhance DNA cleavage mediated by topoisomerase IIalpha except at very high concentrations. However, the activity and potency of the metabolite were dramatically enhanced under oxidizing conditions. These results suggest that topoisomerase IIalpha may play a role in mediating the cytotoxic effects of these fungal metabolites. PMID- 26894875 TI - The anticonvulsant action of the galanin receptor agonist NAX-5055 involves modulation of both excitatory- and inhibitory neurotransmission. AB - The endogenous neuropeptide galanin is ubiquitously expressed throughout the mammalian brain. Through the galanin receptors GalR1-3, galanin has been demonstrated to modulate both glutamatergic and GABAergic neurotransmission, and this appears to be important in epilepsy and seizure activity. Accordingly, galanin analogues are likely to provide a new approach to seizure management. However, since peptides are generally poor candidates for therapeutic agents due to their poor metabolic stability and low brain bioavailability, a search for alternative strategies for the development of galanin-based anti-convulsant drugs was prompted. Based on this, a rationally designed GalR1 preferring galanin analogue, NAX-5055, was synthesized. This compound demonstrates anti-convulsant actions in several animal models of epilepsy. However, the alterations at the cellular level leading to this anti-convulsant action of NAX-5055 are not known. Here we investigate the action of NAX-5055 at the cellular level by determining its effects on excitatory and inhibitory neurotransmission, i.e. vesicular release of glutamate and GABA, respectively, in cerebellar, neocortical and hippocampal preparations. In addition, its effects on cell viability and neurotransmitter transporter capacity were examined to evaluate potential cell toxicity mediated by NAX-5055. It was found that vesicular release of glutamate was reduced concentration-dependently by NAX-5055 in the range from 0.1 to 1000 nM. Moreover, exposure to 1 MUM NAX-5055 led to a reduction in the extracellular level of glutamate and an elevation of the extracellular level of GABA. Altogether these findings may at least partly explain the anti-convulsant effect of NAX-5055 observed in vivo. PMID- 26894877 TI - Composite film polarizer based on the oriented assembly of electrospun nanofibers. AB - Polarizers are widely applied in antiglare glasses, planner displays, photography filters and optical communications, etc. In this investigation, we propose a new strategy for the preparation of a flexible film polarizer based on the electrospinning technique. An aligned assembly of polyvinyl acetate (PVA) nanofibers was electrospun and collected by a fast-rotating drum, then soaked in polymethyl methacrylate (PMMA) solution and dried thoroughly to obtain a transparent PVA-PMMA composite film polarizer. The morphology, structure and optical performance of the PVA nanofibers and the film polarizers were characterized with a scanning electron microscope, UV-vis-IR spectrometer and polarized Raman spectra, etc. The PVA-PMMA film polarizer demonstrated efficient polarizing activity toward visible and near-infrared light, while keeping fair transparency in the range of 400-1400 nm. Due to the protection from the hydrophobic PMMA matrix, the PVA-PMMA film polarizers show high moisture resistance, making it applicable in a humid environment. Considering the scalability and versatility of the strategy employed here, the PVA-PMMA film polarizer prepared could replace the conventional film polarizers in a wide range of applications. PMID- 26894876 TI - Impact of Influenza on Outpatient Visits, Hospitalizations, and Deaths by Using a Time Series Poisson Generalized Additive Model. AB - BACKGROUND: The disease burden associated with influenza in developing tropical and subtropical countries is poorly understood owing to the lack of a comprehensive disease surveillance system and information-exchange mechanisms. The impact of influenza on outpatient visits, hospital admissions, and deaths has not been fully demonstrated to date in south China. METHODS: A time series Poisson generalized additive model was used to quantitatively assess influenza like illness (ILI) and influenza disease burden by using influenza surveillance data in Zhuhai City from 2007 to 2009, combined with the outpatient, inpatient, and respiratory disease mortality data of the same period. RESULTS: The influenza activity in Zhuhai City demonstrated a typical subtropical seasonal pattern; however, each influenza virus subtype showed a specific transmission variation. The weekly ILI case number and virus isolation rate had a very close positive correlation (r = 0.774, P < 0.0001). The impact of ILI and influenza on weekly outpatient visits was statistically significant (P < 0.05). We determined that 10.7% of outpatient visits were associated with ILI and 1.88% were associated with influenza. ILI also had a significant influence on the hospitalization rates (P < 0.05), but mainly in populations <25 years of age. No statistically significant effect of influenza on hospital admissions was found (P > 0.05). The impact of ILI on chronic obstructive pulmonary disease (COPD) was most significant (P < 0.05), with 33.1% of COPD-related deaths being attributable to ILI. The impact of influenza on the mortality rate requires further evaluation. CONCLUSIONS: ILI is a feasible indicator of influenza activity. Both ILI and influenza have a large impact on outpatient visits. Although ILI affects the number of hospital admissions and deaths, we found no consistent influence of influenza, which requires further assessment. PMID- 26894878 TI - Correction: A Proposal for a Comprehensive Grading of Parkinson's Disease Severity Combining Motor and Non-Motor Assessments: Meeting an Unmet Need. PMID- 26894881 TI - Phenotypic Heterogeneity and the Evolution of Bacterial Life Cycles. AB - Most bacteria live in colonies, where they often express different cell types. The ecological significance of these cell types and their evolutionary origin are often unknown. Here, we study the evolution of cell differentiation in the context of surface colonization. We particularly focus on the evolution of a 'sticky' cell type that is required for surface attachment, but is costly to express. The sticky cells not only facilitate their own attachment, but also that of non-sticky cells. Using individual-based simulations, we show that surface colonization rapidly evolves and in most cases leads to phenotypic heterogeneity, in which sticky and non-sticky cells occur side by side on the surface. In the presence of regulation, cell differentiation leads to a remarkable set of bacterial life cycles, in which cells alternate between living in the liquid and living on the surface. The dominant life stage is formed by the surface-attached colony that shows many complex features: colonies reproduce via fission and by producing migratory propagules; cells inside the colony divide labour; and colonies can produce filaments to facilitate expansion. Overall, our model illustrates how the evolution of an adhesive cell type goes hand in hand with the evolution of complex bacterial life cycles. PMID- 26894883 TI - Tensiometric and Phase Domain Behavior of Lung Surfactant on Mucus-like Viscoelastic Hydrogels. AB - Lung surfactant has been observed at all surfaces of the airway lining fluids and is an important contributor to normal lung function. In the conducting airways, the surfactant film lies atop a viscoelastic mucus gel. In this work, we report on the characterization of the tensiometric and phase domain behavior of lung surfactant at the air-liquid interface of mucus-like viscoelastic gels. Poly(acrylic acid) hydrogels were formulated to serve as a model mucus with bulk rheological properties that matched those of tracheobronchial mucus secretions. Infasurf (Calfactant), a commercially available pulmonary surfactant derived from calf lung extract, was spread onto the hydrogel surface. The surface tension lowering ability and relaxation of Infasurf films on the hydrogels was quantified and compared to Infasurf behavior on an aqueous subphase. Infasurf phase domains during surface compression were characterized by fluorescence microscopy and phase shifting interferometry. We observed that increasing the bulk viscoelastic properties of the model mucus hydrogels reduced the ability of Infasurf films to lower surface tension and inhibited film relaxation. A shift in the formation of Infasurf condensed phase domains from smaller, more spherical domains to large, agglomerated, multilayer structures was observed with increasing viscoelastic properties of the subphase. These studies demonstrate that the surface behavior of lung surfactant on viscoelastic surfaces, such as those found in the conducting airways, differs significantly from aqueous, surfactant-laden systems. PMID- 26894882 TI - Protective Effect of Tempol on Acute Kidney Injury Through PI3K/Akt/Nrf2 Signaling Pathway. AB - BACKGROUND/AIMS: Tempol is a protective antioxidant against ischemic injury in many animal models. The molecular mechanisms are not well understood. Nuclear factor erythroid 2-related factor (Nrf2) is a master transcription factor during oxidative stress, which is enhanced by activation of protein kinase C (PKC) pathway. Another factor, tubular epithelial apoptosis, is mediated by activation of phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB, Akt) signaling pathway during renal ischemic injury. We tested the hypothesis that tempol activates PKC or PI3K/Akt/Nrf2 pathways to transcribe many genes that coordinate endogenous antioxidant defense. METHODS: The right renal pedicle was clamped for 45 minutes and the left kidney was removed to study renal ischemia/reperfusion (I/R) injury in C57BL/6 mice. The response was assessed from serum parameters, renal morphology and renal expression of PKC, phosphorylated-PKC (p-PKC), Nrf2, heme oxygenase-1 (HO-1), Akt, phosphorylated-Akt (p-Akt), pro-caspase-3 and cleaved caspase-3 in groups of sham and I/R mice given vehicle, or tempol (50 or 100 mg/kg, intraperitoneal injection). RESULTS: The serum malondialdehyde (MDA, marker of reactive oxygen species) doubled and the BUN and creatinine increased 5 to 10-fold after I/R injury. Tempol (50 or 100 mg/kg) prevented the increases in MDA but only tempol (50 mg/kg) lessened the increases in BUN and creatinine and moderated the acute tubular necrosis. I/R did not change expression of PKC or p PKC but reduced renal expression of Nrf2, p-Akt, HO-1 and pro-caspase-3 and increased cleaved caspase-3. Tempol (50 mg/kg) prevented these changes produced by I/R whereas tempol (100 mg/kg) had lesser or inconsistent effects. CONCLUSION: Tempol (50 mg/kg) prevents lipid peroxidation and attenuates renal damage after I/R injury. The beneficial pathway apparently is not dependent on upregulation or phosphorylation of PKC, at lower tempol doses, does implicate upregulation of Akt with expression of Nrf2 that could account for the increase in the antioxidant gene HO-1 and a reduction in the cleavage of the cellular damage marker pro caspase-3. PMID- 26894884 TI - Decision-Making, Cognitive Distortions and Alcohol Use in Adolescent Problem and Non-problem Gamblers: An Experimental Study. AB - In the psychological literature, many studies have investigated the neuropsychological and behavioral changes that occur developmentally during adolescence. These studies have consistently observed a deficit in the decision making ability of children and adolescents. This deficit has been ascribed to incomplete brain development. The same deficit has also been observed in adult problem and pathological gamblers. However, to date, no study has examined decision-making in adolescents with and without gambling problems. Furthermore, no study has ever examined associations between problem gambling, decision making, cognitive distortions and alcohol use in youth. To address these issues, 104 male adolescents participated in this study. They were equally divided in two groups, problem gamblers and non-problem gamblers, based on South Oaks Gambling Screen Revised for Adolescents scores. All participants performed the Iowa gambling task and completed the Gambling Related Cognitions Scale and the alcohol use disorders identification test. Adolescent problem gamblers displayed impaired decision-making, reported high cognitive distortions, and had more problematic alcohol use compared to non-problem gamblers. Strong correlations between problem gambling, alcohol use, and cognitive distortions were observed. Decision-making correlated with interpretative bias. This study demonstrated that adolescent problem gamblers appear to have the same psychological profile as adult problem gamblers and that gambling involvement can negatively impact on decision-making ability that, in adolescence, is still developing. The correlations between interpretative bias and decision-making suggested that the beliefs in the ability to influence gambling outcomes may facilitate decision-making impairment. PMID- 26894885 TI - Acrolein Inhalation Alters Myocardial Synchrony and Performance at and Below Exposure Concentrations that Cause Ventilatory Responses. AB - Acrolein is an irritating aldehyde generated during combustion of organic compounds. Altered autonomic activity has been documented following acrolein inhalation, possibly impacting myocardial synchrony and function. Given the ubiquitous nature of acrolein in the environment, we sought to better define the immediate and delayed functional cardiac effects of acrolein inhalation in vivo. We hypothesized that acrolein inhalation would increase markers of cardiac mechanical dysfunction, i.e., myocardial dyssynchrony and performance index in mice. Male C57Bl/6J mice were exposed to filtered air (FA) or acrolein (0.3 or 3.0 ppm) for 3 h in whole-body plethysmography chambers (n = 6). Echocardiographic analyses were performed 1 day before exposure and at 1 and 24 h post-exposure. Speckle tracking echocardiography revealed that circumferential strain delay (i.e., dyssynchrony) was increased at 1 and 24 h following exposure to 3.0 ppm, but not 0.3 ppm, when compared to pre-exposure and/or FA exposure. Pulsed wave Doppler of transmitral blood flow revealed that acrolein exposure at 0.3 ppm, but not 3.0 ppm, increased the Tei index of myocardial performance (i.e., decreased global heart performance) at 1 and 24 h post-exposure compared to pre-exposure and/or FA exposure. We conclude that short-term inhalation of acrolein can acutely modify cardiac function in vivo and that echocardiographic evaluation of myocardial synchrony and performance following exposure to other inhaled pollutants could provide broader insight into the health effects of air pollution. PMID- 26894886 TI - The Impact of Mast Cell Density on the Progression of Bone Disease in Multiple Myeloma Patients. AB - BACKGROUND: Osteolytic bone disease is a major hallmark in multiple myeloma (MM) progression and affects many patients. Several inflammatory cells are involved in MM progression. Among them, mast cells (MCs) accumulated in the bone marrow (BM) microenvironment are known to play an important role in the mechanism of neovascularization. METHODS: In 52 newly diagnosed active MM patients, we measured BM MC density (MCD) using an immunohistochemical stain for tryptase, serum levels of matrix metalloproteinase-9 (MMP-9) and receptor activator of nuclear factor x03BA;B ligand (RANKL) by a solid-phase sandwich enzyme-linked immunosorbent assay, along with urine levels of N-terminal propeptide of procollagen type I (Ntx) by a competitive inhibition enzyme-linked immunosorbent assay, in various clinical stages and skeletal grades. RESULTS: MCD, RANKL and Ntx were higher in MM patients. All values increased in association with both the clinical stage and skeletal grade. Furthermore, MCD correlated positively with MMP-9, RANKL and Ntx. CONCLUSIONS: Our data suggest that MCs may contribute to osteolytic processes during MM progression. Although the major role of MCs in tumor progression is to enhance angiogenesis, it seems that they may affect MM bone disease and may secrete a plethora of mediators that may directly and indirectly have an impact on osteolysis. PMID- 26894888 TI - Target Plate Material Influence on Fullerene-C60 Laser Desorption/Ionization Efficiency. AB - Systematic laser desorption/ionization (LDI) experiments of fullerene-C60 on a wide range of target plate materials were conducted to gain insight into the initial ion formation in matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. The positive and negative ion signal intensities of precursor, fragment, and cluster ions were monitored, varying both the laser fluence (0-3.53 Jcm(-2)) and the ion extraction delay time (0-950 ns). The resulting species specific ion signal intensities are an indication for the ionization mechanisms that contribute to LDI and the time frames in which they operate, providing insight in the (MA)LDI primary ionization. An increasing electrical resistivity of the target plate material increases the fullerene-C60 precursor and fragment anion signal intensity. Inconel 625 and Ti90/Al6/V4, both highly electrically resistive, provide the highest anion signal intensities, exceeding the cation signal intensity by a factor ~1.4 for the latter. We present a mechanism based on transient electrical field strength reduction to explain this trend. Fullerene C60 cluster anion formation is negligible, which could be due to the high extraction potential. Cluster cations, however, are readily formed, although for high laser fluences, the preferred channel is formation of precursor and fragment cations. Ion signal intensity depends greatly on the choice of substrate material, and careful substrate selection could, therefore, allow for more sensitive (MA)LDI measurements. Graphical Abstract ?. PMID- 26894887 TI - Human Islet Amyloid Polypeptide N-Terminus Fragment Self-Assembly: Effect of Conserved Disulfide Bond on Aggregation Propensity. AB - Amyloid formation by human islet amyloid polypeptide (hIAPP) has long been implicated in the pathogeny of type 2 diabetes mellitus (T2DM) and failure of islet transplants, but the mechanism of IAPP self-assembly is still unclear. Numerous fragments of hIAPP are capable of self-association into oligomeric aggregates, both amyloid and non-amyloid in structure. The N-terminal region of IAPP contains a conserved disulfide bond between cysteines at position 2 and 7, which is important to hIAPP's in vivo function and may play a role in in vitro aggregation. The importance of the disulfide bond in this region was probed using a combination of ion mobility-based mass spectrometry experiments, molecular dynamics simulations, and high-resolution atomic force microscopy imaging on the wildtype 1-8 hIAPP fragment, a reduced fragment with no disulfide bond, and a fragment with both cysteines at positions 2 and 7 mutated to serine. The results indicate the wildtype fragment aggregates by a different pathway than either comparison peptide and that the intact disulfide bond may be protective against aggregation due to a reduction of inter-peptide hydrogen bonding. Graphical Abstract ?. PMID- 26894889 TI - When is Sessional Monitoring More Likely in Child and Adolescent Mental Health Services? AB - Sessional monitoring of patient progress or experience of therapy is an evidence based intervention recommended by healthcare systems internationally. It is being rolled out across child and adolescent mental health services (CAMHS) in England to inform clinical practice and service evaluation. We explored whether patient demographic and case characteristics were associated with the likelihood of using sessional monitoring. Multilevel regressions were conducted on N = 2609 youths from a routinely collected dataset from 10 CAMHS. Girls (odds ratio, OR 1.26), older youths (OR 1.10), White youths (OR 1.35), and youths presenting with mood (OR 1.46) or anxiety problems (OR 1.59) were more likely to have sessional monitoring. In contrast, youths under state care (OR 0.20) or in need of social service input (OR 0.39) were less likely to have sessional monitoring. Findings of the present research may suggest that sessional monitoring is more likely with common problems such as mood and anxiety problems but less likely with more complex cases, such as those involving youths under state care or those in need of social service input. PMID- 26894890 TI - IGF-1 protects dopamine neurons against oxidative stress: association with changes in phosphokinases. AB - Insulin-like growth factor-1 (IGF-1) is an endogenous peptide transported across the blood brain barrier that is protective in several brain injury models, including an acute animal model of Parkinson's disease (PD). Motor deficits in PD are due largely to the progressive loss of nigrostriatal dopaminergic neurons. Thus, we examined the neuroprotective potential of IGF-1 in a progressive model of dopamine deficiency in which 6-hydroxydopamine (6-OHDA) is infused into the striatum. Rats received intrastriatal IGF-1 (5 or 50 ug) 6 h prior to infusion of 4 ug 6-OHDA into the same site and were euthanized 1 or 4 weeks later. Both concentrations of IGF-1 protected tyrosine hydroxylase (TH) immunoreactive terminals in striatum at 4 weeks but not at 1 week, indicating that IGF-induced restoration of the dopaminergic phenotype occurred over several weeks. TH immunoreactive cell loss was only attenuated with 50 ug IGF-1. We then examined the effect of striatal IGF-1 on the Ras/ERK1/2 and PI3K/Akt pathways to ascertain whether their activation correlated with IGF-1-induced protection. Striatal and nigral levels of phospho-ERK1/2 were maximal 6 h after IGF-1 infusion and, with the exception of an increase in nigral pERK2 at 48 h, returned to basal levels by 7 days. Phospho-Akt (Ser473) was elevated 6-24 h post-IGF-1 infusion in both striatum and substantia nigra concomitant with inhibition of pro-death GSK-3beta, a downstream target of Akt. These results suggest that IGF-1 can protect the nigrostriatal pathway in a progressive PD model and that this protection is preceded by activation of key pro-survival signaling cascades. PMID- 26894892 TI - Cognition overrides orientation dependence in tactile viewpoint selection. AB - Humans are capable of extracting spatial information through their sense of touch: when someone strokes their hand, they can easily determine stroke direction without visual information. However, when it comes to the coordinate system used to assign the spatial relations to the stimulation, it remains poorly understood how the brain selects the appropriate system for passive touch. In the study reported here, we investigated whether hand orientation can determine coordinate assignment to ambiguous tactile patterns, whether observers can cognitively override any orientation-driven perspectives on touch, and whether the adaptation transfers across body surfaces. Our results demonstrated that the orientation of the hand in the vertical plane determines the perspective taken: an external perspective is adopted when the hand faces the observer and a gaze centred perspective is selected when the hand faces away. Participants were then adapted to a mirror-reversed perspective through training, and the results revealed that this adapted perspective holds for the adapted surface and generalises to non-adapted surfaces, including across the body midline. These results reveal plasticity in perspective taking which relies on low-level postural cues (hand orientation) but also on higher-order somatosensory processing that can override the low-level cues. PMID- 26894891 TI - Approaching threat modulates visuotactile interactions in peripersonal space. AB - The region surrounding our body (i.e. peripersonal space) is coded in a multimodal representation by fronto-parietal bimodal neurons integrating tactile stimuli on the body with nearby visual stimuli. This has often been suggested to serve a defensive purpose, which we propose could be mediated through visuotactile predictions. An approaching threat would then be of particular interest to peripersonal space processing. To investigate this, we asked participants to respond as fast as possible to a tactile stimulus on the hand, while looking at an animation of an approaching or receding spider or butterfly. Tactile stimulation was applied at one of 25 possible time points during the animation. Tactile reaction times were faster when an approaching stimulus was closer to the hand at the time of tactile presentation. Critically, this effect of distance on reaction times was larger when participants saw an approaching spider compared to an approaching butterfly, but only for participants who were afraid of spiders. This finding demonstrates that the perceived threat of an approaching stimulus modulates visuotactile interactions in peripersonal space and is consistent with the idea that visuotactile predictions are important for defensive purposes and maintaining bodily integrity. PMID- 26894893 TI - Survey of student perception of medical education environment among emergency medicine residents of an academic medical centre in Northern India. AB - BACKGROUND: The specialty of emergency medicine is in its infancy state in the long history of the Indian health sciences education system. Little analytical published data is available at the moment in India regarding the quality of medical education as perceived by the students. Roff et al. (Med Teach 19: 295 299, 1997) developed a methodology using a Delphi panel to standardize the measurement of medical education known as the Dundee Ready Education Environment Measure (DREEM), which is widely utilized. The purpose of this survey is to investigate student perceptions of medical education environment among emergency medicine residents of an academic medical centre in Northern India using the DREEM tool. METHODS: The DREEM questionnaire was administered to the students undergoing 3-year post-graduate emergency medicine training in our residency programme. A total of 35 students enrolled from all 3 years of the residency programme completed the survey in May 2013. The results were analysed using STATA 9.0. RESULTS: The reliability coefficient which was calculated using Cronbach's alpha for the totality of items of this study was 0.92, which indicates high internal consistency. The mean (95 % CI) for the overall DREEM was 139.8 (133.3, 146.2), which showed excellent educational environment among the medical students. CONCLUSIONS: The DREEM score is a universal tool for assessment of education provided by health science institutes. With a total score of 139.8, the study conducted at our institute showed comparable results to the original DREEM study conducted by Roff et al. The good scores in all the five subscales reveal an excellent educational programme and learning environment as perceived by the students enrolled at our institution. PMID- 26894894 TI - Analysis of trauma admission data at an urban hospital in Maputo, Mozambique. AB - BACKGROUND: Trauma is a major public health concern. Worldwide, injuries resulted in 4.8 million deaths in 2013, an increase of 11 % since 1990. The majority of deaths from trauma in low-and middle-income countries occur in a pre-hospital setting. Morbidity from trauma contributes significantly to disability in these countries. Mozambique has experienced a rise in injury-related morbidity and mortality. Efforts are underway to prioritize surgical and anesthesiology care in the post-2015 Global Surgery agenda that will build on momentum of the Millennium Development Goals. Injury surveillance remains vital to defining priorities and implementing policy changes. METHODS: We performed a cross-sectional study between June and September, 2010 at the Hospital Central de Maputo (HCM). Data were collected on all patients admitted to the HCM emergency surgical services with a diagnosis of trauma. We describe patient characteristics and mechanism of traumatic injury by calculating simple proportions (for dichotomous or categorical variables) or medians with interquartile ranges (IQR) for continuous variables. Multivariable logistic regression analysis was used to estimate the mechanisms of trauma most associated with alcohol consumption. RESULTS: A total of 517 patients were approached for inclusion in this study. Of these, 441 (91.5 %) participants were followed from admission until discharge. Three hundred twenty-four participants (73.5 %) were male. The most common age group was 20-29 years old. The three principal mechanisms of injury were road traffic injury, fighting, and falls, accounting for 74 % of injuries recorded. Traumatic injury involving alcohol consumption was nine times more likely to occur at a recreation/sporting event (OR 9.0, 95 % CI 3.01-27.13, p <= 0.0001). CONCLUSIONS: As Mozambique prepares to respond to the post-2015 international development agenda, urgent action is required to scale-up its national injury surveillance networks. Injury prevention efforts in Mozambique should focus attention on improving road safety regulations and their implementation, as well as on interventions targeting violence reduction and the reduction of alcohol consumption at sporting events. PMID- 26894895 TI - Point-of-care capillary HbA1c measurement in the emergency department: a useful tool to detect unrecognized and uncontrolled diabetes. AB - BACKGROUND: Inpatient hyperglycaemia and diabetes mellitus (DM) are common and are associated with an increased risk of complications and mortality. The severity of hyperglycaemia determines the rate of complications in patients treated in the emergency department (ED). Our aim was to examine whether determination of the capillary haemoglobin A1c (HbA1c) is a reliable method for detecting unknown diabetes and poor glycaemic control in the ED. METHODS: A prospective observational study was conducted in adult (>18 years) patients treated in a single-centre ED. We compared the results of HbA1c levels measured by Bio-Rad in2it point-of-care device on a capillary blood sample and by the hospital laboratory. RESULTS: A total of 187 ED patients with an average age of 57.1 +/- 19.2 years were studied. The mean HbA1c value was 5.78 +/- 1.26 % by capillary POC testing and 6.10 +/- 1.12 % by the hospital laboratory (correlation = 0.712, P < 0.001). A total of 17.1 % of cases had a prior diagnosis of DM. The diagnosis of DM (plasma glucose > 126 mg/dL and/or HbA1c > 6.5 %) was made in ten (5.4 %) additional cases (prior undiagnosed DM) for a total prior DM prevalence of 22.5 % (95 % CI 16.4-28.5 %). Capillary HbA1c detected 11 additional cases of unknown DM (5.9 %). A capillary HbA1c value greater than 6 % has a sensitivity of 85.7 % and specificity of 85.3 % for the screening of DM. CONCLUSIONS: Determination of the capillary HbA1c in the ED is a reliable, fast, and simple system for the screening of unknown or uncontrolled DM. PMID- 26894896 TI - Ultrasonographic assessment of inferior vena cava/abdominal aorta diameter index: a new approach of assessing hypovolemic shock class 1. AB - BACKGROUND: We designed this study to expand the usage of ultrasound to detect early occurrence of hypovolemia. We explore the potential use of inferior vena cava (IVC) and abdominal aorta (AA) diameter index (IVC:AA) measured ultrasonographically to detect class 1 hypovolemic shock with blood loss less than 15%.? METHODS: The aim of this study was to determine the changes in the diameter of inferior vena cava and abdominal aorta in blood donors by using ultrasound, pre and post blood donation. The result of the study would be further explorated to determine the inferior vena cava (IVC) abdominal aorta (Aorta) diameter index (IVC:Aorta). This was a prospective study done in the blood bank of a university hospital. Researcher was trained by a senior radiologist to assess inferior vena cava and abdominal aorta diameter. Fifty-two healthy blood donors were included in the study. Inclusion criteria were same with the blood bank criteria to donate blood. Demographic data and vital signs were taken before the ultrasound measurement done for inferior vena cava and abdominal aorta diameter. Once the volunteers donated their blood of approximately 450 mls; the measurements were repeated using the same methods. RESULTS: There were differences in IVC, abdominal aorta and inferior vena cava:aorta diameters index pre and post donation. With mathematical analysis, we suggested the number of IVC:Aorta index as 1.14+/-2SD with SD 0.18 as a cut off value for class 1 hypovolemic shock. CONCLUSION: The IVC:Aorta diameter index can be used as a parameter for detecting early phase (Class 1) of hypovolemic shock. PMID- 26894899 TI - Editor's Notes. PMID- 26894898 TI - Energetics of Transport through the Nuclear Pore Complex. AB - Molecular transport across the nuclear envelope in eukaryotic cells is solely controlled by the nuclear pore complex (NPC). The NPC provides two types of nucleocytoplasmic transport: passive diffusion of small molecules and active chaperon-mediated translocation of large molecules. It has been shown that the interaction between intrinsically disordered proteins that line the central channel of the NPC and the transporting cargoes is the determining factor, but the exact mechanism of transport is yet unknown. Here, we use coarse-grained molecular dynamics simulations to quantify the energy barrier that has to be overcome for molecules to pass through the NPC. We focus on two aspects of transport. First, the passive transport of model cargo molecules with different sizes is studied and the size selectivity feature of the NPC is investigated. Our results show that the transport probability of cargoes is significantly reduced when they are larger than ~5 nm in diameter. Secondly, we show that incorporating hydrophobic binding spots on the surface of the cargo effectively decreases the energy barrier of the pore. Finally, a simple transport model is proposed which characterizes the energy barrier of the NPC as a function of diameter and hydrophobicity of the transporting particles. PMID- 26894900 TI - Inspiring and Equipping Students to Be Ethical Leaders. AB - This chapter describes the behaviors of the ethical leader and explores the reasons why leaders do not always act ethically. The chapter also offers five recommendations to help educators integrate the practices of ethical leadership into their work with student leaders. PMID- 26894901 TI - Building Moral Strength: Bridging the Moral Judgment-Action Gap. AB - This chapter reviews the literature on the moral self and student development and highlights the best practices for enhancing students' moral strength. PMID- 26894902 TI - Learning About Ethical Leadership Through the Giving Voice to Values Curriculum. AB - This chapter explores the Giving Voice to Values curriculum, one innovative approach to integrating ethics into leadership development. The chapter describes how Giving Voice to Values is being used in educational settings across the globe. PMID- 26894903 TI - At What Age Should We Begin Developing Ethical Leaders? AB - This chapter is about a unique partnership between Ravenscroft, a pre-K-12th grade independent school in Raleigh, North Carolina, and the Center for Creative Leadership. Starting in pre-K, Ravenscroft students embark on the Lead From Here initiative that inspires and empowers them to become citizen leaders. PMID- 26894904 TI - When Leading With Integrity Goes Well: Integrating the Mind, Body, and Heart. AB - The science and application of mindfulness is critical for helping leaders to make ethical decisions. The chapter offers three models that educators can use to connect the new science of well-being and mindfulness to ethical behavior. PMID- 26894905 TI - Making Moral Mistakes: What Ethical Failure Can Teach Students About Life and Leadership. AB - Learning from ethical failures is critical for overall character development as well as an important aspect in the formation of student leaders. This chapter examines types of ethical failure that students often confront in college. The author includes a personal moral failure that occurred when he was a student leader. PMID- 26894906 TI - A Critical Review of Theories and Measures of Ethics-Related Leadership. AB - This chapter reviews the different theoretical perspectives and measurements of ethics-related leadership models, including ethical leadership, transformational leadership, authentic leadership, servant leadership, spiritual leadership, and a virtues-based approach to leadership ethics. The similarities and differences among these theoretical models and measures to ethics-related leadership are discussed. PMID- 26894907 TI - Effects of biosolids and compost amendment on chemistry of soils contaminated with copper from mining activities. AB - Several million metric tons of mining wastes, called stamp sands, were generated in the Upper Peninsula of Michigan during extensive copper (Cu) mining activities in the past. These materials, containing large amounts of Cu, were discharged into various offshoots of Lake Superior. Due to evidences of Cu toxicity on aquatic organisms, in due course, the materials were dredged and dumped on lake shores, thus converting these areas into vast, fallow lands. Erosion of these Cu contaminated stamp sands back to the lakes is severely affecting aquatic life. A lack of uniform vegetation cover on stamp sands is facilitating this erosion. Understanding the fact that unless the stamp sands are fertilized to the point of sustaining vegetation growth, the problem with erosion and water quality degradation will continue, amending the stamp sands with locally available biosolids and composts, was considered. The purpose of the reported study was to assess potential effects of such organic fertilizer amendments on soil quality. As the first step of a combined laboratory and greenhouse study, a 2-month-long incubation experiment was performed to investigate the effects of biosolids and compost addition on the soil nutrient profile of stamp sands and organic matter content. Results showed that both biosolids and compost amendments resulted in significant increase in nitrogen and phosphorus concentrations and organic matter contents of stamp sands. Sequential extraction data demonstrated that Cu was mostly present as bound forms in stamp sands, and there was no significant increase in the plant available fraction of Cu because of fertilizer application. PMID- 26894897 TI - Pathogenesis of nonalcoholic steatohepatitis. AB - Nonalcoholic steatohepatitis (NASH) is a severe form of nonalcoholic fatty liver disease and a risk factor for cirrhosis and hepatocellular carcinoma. The pathological features of NASH include steatosis, hepatocyte injury, inflammation, and various degrees of fibrosis. Steatosis reflects disordered lipid metabolism. Insulin resistance and excessive fatty acid influx to the liver are two important contributing factors. Steatosis is also likely associated with lipotoxicity and cellular stresses such as oxidative stress and endoplasmic reticulum stress, which result in hepatocyte injury. Inflammation and fibrosis are frequently triggered by various signals such as proinflammatory cytokines and chemokines, released by injuried hepatocytes and activated Kupffer cells. Although much progress has been made, the pathogenesis of NASH is not fully elucidated. The purpose of this review is to discuss the current understanding of NASH pathogenesis, mainly focusing on factors contributing to steatosis, hepatocyte injury, inflammation, and fibrosis. PMID- 26894908 TI - Postoperative Early Major and Minor Complications in Laparoscopic Vertical Sleeve Gastrectomy (LVSG) Versus Laparoscopic Roux-en-Y Gastric Bypass (LRYGB) Procedures: A Meta-Analysis and Systematic Review. AB - BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic vertical sleeve gastrectomy (LVSG) have been proposed as cost-effective strategies to manage obesity-related chronic disease. The aim of this meta analysis and systematic review was to compare the "early postoperative complication rate i.e. within 30-days" reported from randomized control trials (RCTs) comparing these two procedures. METHODS: RCTs comparing the early complication rates following LVSG and LRYGB between 2000 and 2015 were selected from PubMed, Medline, Embase, Science Citation Index, Current Contents, and the Cochrane database. The outcome variables analyzed included 30-day mortality, major and minor complications and interventions required for their management, length of hospital stay, readmission rates, operating time, and conversions from laparoscopic to open procedures. RESULTS: Six RCTs involving a total of 695 patients (LVSG n = 347, LRYGB n = 348) reported on early major complications. A statistically significant reduction in relative odds of early major complications favoring the LVSG procedure was noted (p = 0.05). Five RCTs representing 633 patients (LVSG n = 317, LRYGB n = 316) reported early minor complications. A non statically significant reduction in relative odds of 29 % favoring the LVSG procedure was observed for early minor complications (p = 0.4). However, other outcomes directly related to complications which included reoperation rates, readmission rate, and 30-day mortality rate showed comparable effect size for both surgical procedures. CONCLUSIONS: This meta-analysis and systematic review of RCTs suggests that fewer early major and minor complications are associated with LVSG compared with LRYGB procedure. However, this does not translate into higher readmission rate, reoperation rate, or 30-day mortality for either procedure. PMID- 26894909 TI - The Effects of Bariatric Procedures on Bowel Habit. AB - BACKGROUND: Bariatric procedures are increasingly being used to combat the rising obesity epidemic. The aim of this study was to assess the effect of these interventions on bowel habit. METHODS: We recruited obese adults listed for a bariatric procedure. Demographic data, medical history, medications and anthropometric measurements were recorded. Bowel habit was characterized using a 7-day Bristol Stool Form Scale (BSFS) diary. A validated food frequency questionnaire (FFQ) was used to assess diet. RESULTS: Twenty-six patients were assessed pre-operatively and at a median of 6.4 months post-operatively. Nineteen had a Roux-en-Y gastric bypass (RYGB), five had a sleeve gastrectomy (SG) and two had an intra-gastric balloon (IGB) with median percentage excess weight loss (% EWL) of 67.9, 52.4 and 31.3 %, respectively. Dietary fibre intake decreased from 24.4 (+/-12.1) g/day pre-operatively to 17.5 (+/-7.3) g/day post-operatively (P = 0.008). Frequency of bowel motions decreased from 8.6 (+/-3.5) to 5.7 (+/-3.5) motions/week (P = 0.001). Mean usual BSFS score decreased (towards firmer stool) from 4.1 (+/-1.3) pre-operatively to 3.1 (+/-1.9) post-operatively (P = 0.016). Constipation increased from 8 to 27 %, but this did not reach statistical significance (P = 0.125). CONCLUSIONS: Constipation is a common problem after bariatric surgery. The decrease in bowel motion frequency and change towards firmer stools suggest prolonged intestinal transit time after bariatric procedures. Reduction in dietary fibre intake is likely to be a contributory factor. PMID- 26894910 TI - Ultrasound-guided retro-calcaneal bursa corticosteroid injection for refractory Achilles tendinitis in patients with seronegative spondyloarthropathy: efficacy and follow-up study. AB - Ultrasound (US)-guided corticosteroid injection has been shown to be safe and effective for varied causes of plantar fasciitis; however, its use for Achilles tendinitis is controversial. We studied the efficacy and changes in US findings at Achilles enthesitis after corticosteroid injection in patients with spondyloarthropathy (SpA). Patients with SpA with symptomatic Achilles enthesitis, refractory to 6 weeks of full-dose NSAIDs, were offered US-guided local corticosteroid injection. Injected entheses were examined by US (both B mode and power Doppler) at baseline and 6 weeks after injection. Standard OMERACT definitions were used to define enthesitis. Achilles tendon thickness >5.29 mm, 2 cm proximal to insertion in long axis, was considered thickened. Twenty-seven symptomatic Achilles tendons (in 18 patients) were injected with 20 mg methylprednisolone under US guidance baseline, and 6-week follow-up US features were compared. All patients reported improvement in pain (VAS) in the affected tendon after injection (p < 0.0001). Simultaneously, improvement in local inflammatory changes were noted, in the form of significant reduction in tendon thickness (p < 0.0001), vascularity (p < 0.0001), peritendinous oedema (p = 0.001), bursitis and bursal vascularity (p < 0.001 and < 0.0001, respectively). There was no change in bone erosions and enthesophyte. None of the patients had tendon rupture or other injection-related complications at 6 weeks of follow-up. US-guided local corticosteroid injection is an effective and safe modality for refractory Achilles enthesitis in patients with SpA and leads to reversion of acute changes at entheseal site. PMID- 26894911 TI - Use of a Novel Double-Crested Cormorant ToxChip PCR Array and the EROD Assay to Determine Effects of Environmental Contaminants in Primary Hepatocytes. AB - In vitro screening tools and 'omics methods are increasingly being incorporated into toxicity studies to determine mechanistic effects of chemicals and mixtures. To date, the majority of these studies have been conducted with well characterized laboratory animal models. In the present study, well-established methods developed for chicken embryonic hepatocyte (CEH) studies were extended to a wild avian species, the double-crested cormorant (DCCO; Phalacrocorax auritus), in order to compare the effects of several environmental contaminants on cytotoxicity, ethoxyresorufin O-deethylase (EROD) activity, and mRNA expression. Five organic flame retardants and one plasticizer decreased cormorant hepatocyte viability in a similar manner to that observed in previous studies with CEH. EROD activity was induced in a concentration-dependent manner following exposure to two dioxin-like chemicals and the calculated EC50 values were concordant with domestic avian species from similar species sensitivity categories. Transcriptomic effects were determined using a novel DCCO PCR array, which was designed, constructed and validated in our laboratory based on a commercially available chicken PCR array. The DCCO array has 27 target genes covering a wide range of toxicity pathways. Gene profiles were variable among the 10 chemicals screened; however, good directional concordance was observed with regard to results previously obtained in CEH. Overall, the application of well-established methods (i.e., CEH and chicken PCR array) to the double-crested cormorant demonstrated the portability of the techniques to an indicator species of ecological relevance. PMID- 26894913 TI - Differential pain modulation properties in central neuropathic pain after spinal cord injury. AB - It seems that central neuropathic pain (CNP) is associated with altered abilities to modulate pain; whereas dysfunction in descending pain inhibition is associated with the extent of chronic pain distribution, enhanced pain excitation is associated with the intensity of chronic pain. We investigated the hypothesis that CNP is associated with decreased descending pain inhibition along with increased neuronal excitability and that both traits are associated with spinothalamic tract (STT) damage. Chronic spinal cord injury subjects with CNP (n = 27) and without CNP (n = 23) and healthy controls (n = 20) underwent the measurement of pain adaptation, conditioned pain modulation (CPM), tonic suprathreshold pain (TSP), and spatial summation of pain above injury level. Central neuropathic pain subjects also underwent at and below-lesion STT evaluation and completed the questionnaires. Central neuropathic pain subjects showed decreased CPM and increased enhancement of TSP compared with controls. Among CNP subjects, the dysfunction of CPM and pain adaptation correlated positively with the number of painful body regions. The magnitude of TSP and spatial summation of pain correlated positively with CNP intensity. STT scores correlated with CNP intensity and with TSP, so that the more affected the STT below injury level, the greater the CNP and TSP magnitude. It seems that CNP is associated with altered abilities to modulate pain, whereas dysfunction in descending pain inhibition is associated with the extent of chronic pain distribution and enhanced pain excitation is associated with the intensity of chronic pain. Thus, top-down processes may determine the spread of CNP, whereas bottom-up processes may determine CNP intensity. It also seems that the mechanisms of CNP may involve STT-induced hyperexcitability. Future, longitudinal studies may investigate the timeline of this scenario. PMID- 26894914 TI - Quantitative sensory testing in classical trigeminal neuralgia-a blinded study in patients with and without concomitant persistent pain. AB - The diagnostic criteria of the third International Classification of Headache Disorders state that there should be no neurological deficits in patients with classical trigeminal neuralgia (TN) at clinical examination. However, studies demonstrating sensory abnormalities at bedside examination in TN patients have questioned this. Our aim was to examine whether TN patients without sensory abnormalities at neurological examination have sensory abnormalities at quantitative sensory testing (QST) and whether there were any QST differences between TN with and without concomitant persistent pain. Thirty-six TN patients were investigated with the standardized QST protocol by the German Research Network on Neuropathic Pain. The investigators were blinded to presence of concomitant persistent pain and symptomatic side. Based on comparison to the German Research Network on Neuropathic Pain controls, z scores were calculated to process frequency analyses and Z-profiles. We found increased mechanical detection threshold on the symptomatic side (47.2% vs 0%, P = 0.008), asymptomatic side (33.3% vs 0%, P = 0.011), and hand (36% vs 0%, P < 0.001) in TN compared with controls. The Z-profiles demonstrated increased mechanical detection threshold on the symptomatic side compared with the asymptomatic side ( 2.980 vs -2.166, P = 0.040). Thermal and mechanical hyperalgesia was detected bilaterally in the face and the hand. Trigeminal neuralgia patients with concomitant persistent pain tended to have higher mean z score values compared to TN with purely paroxysmal pain indicative of decreased detection thresholds. Trigeminal neuralgia patients with no sensory abnormalities at neurological examination had generalized subclinical hypoesthesia, which was more pronounced on the symptomatic side, and thermal and mechanical hyperalgesia. This could indicate pain-induced hypoesthesia and sensitization induced by central mechanisms. PMID- 26894912 TI - Targeted overexpression of tumor necrosis factor-alpha increases cyclin-dependent kinase 5 activity and TRPV1-dependent Ca2+ influx in trigeminal neurons. AB - We reported earlier that TNF-alpha, a proinflammatory cytokine implicated in many inflammatory disorders causing orofacial pain, increases the activity of Cdk5, a key kinase involved in brain development and function and recently found to be involved in pain signaling. To investigate a potential mechanism underlying inflammatory pain in trigeminal ganglia (TGs), we engineered a transgenic mouse model (TNF) that can conditionally overexpresses TNF-alpha upon genomic recombination by Cre recombinase. TNF mice were bred with Nav1.8-Cre mouse line that expresses the Cre recombinase in sensory neurons to obtain TNF-alpha:Nav1.8 Cre (TNF-alpha cTg) mice. Although TNF-alpha cTg mice appeared normal without any gross phenotype, they displayed a significant increase in TNF-alpha levels after activation of NFkappaB signaling in the TG. IL-6 and MCP-1 levels were also increased along with intense immunostaining for Iba1 and GFAP in TG, indicating the presence of infiltrating macrophages and the activation of satellite glial cells. TNF-alpha cTg mice displayed increased trigeminal Cdk5 activity, and this increase was associated with elevated levels of phospho-T407-TRPV1 and capsaicin evocated Ca influx in cultured trigeminal neurons. Remarkably, this effect was prevented by roscovitine, an inhibitor of Cdk5, which suggests that TNF-alpha overexpression induced sensitization of the TRPV1 channel. Furthermore, TNF-alpha cTg mice displayed more aversive behavior to noxious thermal stimulation (45 degrees C) of the face in an operant pain assessment device as compared with control mice. In summary, TNF-alpha overexpression in the sensory neurons of TNF alpha cTg mice results in inflammatory sensitization and increased Cdk5 activity; therefore, this mouse model would be valuable for investigating the mechanism of TNF-alpha involved in orofacial pain. PMID- 26894915 TI - Dose-response relationship between sports activity and musculoskeletal pain in adolescents. AB - Physical activity has multiple health benefits but may also increase the risk of developing musculoskeletal pain (MSP). However, the relationship between physical activity and MSP has not been well characterized. This study examined the dose response relationship between sports activity and MSP among adolescents. Two school-based serial surveys were conducted 1 year apart in adolescents aged 12 to 18 years in Unnan, Japan. Self-administered questionnaires were completed by 2403 students. Associations between time spent in organized sports activity and MSP were analyzed cross-sectionally (n = 2403) and longitudinally (n = 374, students free of pain and in seventh or 10th grade at baseline) with repeated-measures Poisson regression and restricted cubic splines, with adjustment for potential confounders. The prevalence of overall pain, defined as having pain recently at least several times a week in at least one part of the body, was 27.4%. In the cross-sectional analysis, sports activity was significantly associated with pain prevalence. Each additional 1 h/wk of sports activity was associated with a 3% higher probability of having pain (prevalence ratio = 1.03, 95% confidence interval = 1.02-1.04). Similar trends were found across causes (traumatic and nontraumatic pain) and anatomic locations (upper limbs, lower back, and lower limbs). In longitudinal analysis, the risk ratio for developing pain at 1-year follow-up per 1 h/wk increase in baseline sports activity was 1.03 (95% confidence interval = 1.02-1.05). Spline models indicated a linear association (P < 0.001) but not a nonlinear association (P >= 0.45). The more the adolescents played sports, the more likely they were to have and develop pain. PMID- 26894916 TI - Locomotor Trajectories of Stroke Patients during Oriented Gait and Turning. AB - BACKGROUND: The Timed Up and Go (TUG) test is widely used to assess locomotion in patients with stroke and is considered to predict the risk of falls. The analysis of locomotor trajectories during the TUG appears pertinent in stroke patients. The aims of this study were i) to analyze locomotor trajectories in patients with stroke during the walking and turning sub-tasks of the TUG, and to compare them with healthy subjects, ii) to determine whether trajectory parameters provide additional information to that provided by the conventional measure (performance time), iii) to compare the trajectory parameters of fallers and non-fallers with stroke and of patients with right and left hemisphere stroke, and iv) to evaluate correlations between trajectory parameters and Berg Balance Scale scores. METHODS: 29 patients with stroke (mean age 54.2+/-12.2 years, 18 men, 8 fallers) and 25 healthy subjects (mean age 51.6+/-8.7 years, 11 men) underwent three dimensional analysis of the TUG. The trajectory of the center of mass was analyzed by calculation of the global trajectory length, Hausdorff distance and Dynamic Time Warping. The parameters were compared with a reference trajectory during the total task and each sub-task (Go, Turn, Return) of the TUG. RESULTS: Values of trajectory parameters were significantly higher for the stroke group during the total TUG and the Go and Turn sub-tasks (p<0.05). Moreover, logistic regression indicated that these parameters better discriminated stroke patients and healthy subjects than the conventional timed performance during the Go sub task. In addition, fallers were distinguished by higher Dynamic Time Warping during the Go (p<0.05). There were no differences between patients with right and left hemisphere stroke. DISCUSSION AND CONCLUSION: The trajectories of the stroke patients were longer and more deviated during the turn and the preceding phase. Trajectory parameters provided additional information to timed performance of this locomotor task. Focusing rehabilitation programs on lead-up to turn and turning could be relevant for stroke patients since the Turn was related to the balance and the phase preceding the turn seemed to distinguish fallers. PMID- 26894917 TI - Effect of pinhole shape on projection resolution. AB - We are designing a dual-resolution pre-clinical SPECT system based on square pinhole apertures for use in applications with a small field-of-view (FOV), such as cardiac imaging of mice. Square pinholes allow for increased sensitivity due to more efficient projection tiling on the detector compared to circular pinholes. Aperture fabrication techniques cannot produce a perfect square, giving the square pinholes some amount of roundedness at the corners. This work investigates how this roundedness affects the physical properties of projection images in terms of spatial resolution. Different pinhole full-acceptance angles and roundedness values were simulated. To facilitate a fair comparison, properties of the non-square pinholes were manipulated to yield pinholes with approximately the same sensitivity (to within 0.1%) and FOV (to within 0.5%) as those of the square pinholes, subsequently referred to as matched apertures. The aperture size (flat-to-flat edge length) of each non-square aperture was increased until its sensitivity was approximately equal to that of the square pinhole. Next, the full acceptance angle was increased until the FOV of each non square aperture was approximately equivalent to that of the square pinhole. Sensitivity was calculated to include both the geometric and penetrative sensitivity of a point source, as well as the packing faction of the multi pinhole collimator. Using the sensitivity-matched and FOV-matched apertures, spatial resolution was estimated. For the 0.3 mm, 0.5 mm, and 1 mm edge-length square apertures studied, the full-width at half-maximum widened as pinhole shape changed from square to circle, while full-width tenth-maximum showed little change. These results indicate that a perfect square pinhole shape is more desirable than a rounded-square pinhole with regard to spatial resolution when sensitivity and FOV-matched pinholes are compared. PMID- 26894918 TI - Identification of combined action types in experiments with two toxicants: a response surface linear model with a cross term. AB - Within the framework of the response surface linear model with a cross term, i.e. a model of the type Y(x1, x2) = b0 + b1x1 + b2x2 + b12x1x2 (hyperbolic paraboloid), a complete solution of identification of combined action types of two toxicants x1 and x2 is presented. It is shown that the type of combined effect in this model is determined by two factors: the direction in which the toxicants act (unidirectional or oppositely directed), and the position of the saddle point S of a hyperbolic paraboloid. For unidirectional actions of toxicants, already-known ways to identify the type of combined effect (including a shape of the isobole: concave-up or concave-down) provided identical and unambiguous answers regarding the type of combined effect (antagonism or synergism). For oppositely directed actions of toxicants, the shape of the isobole (concave-up or concave-down) did not allow us to determine the type of combined action type unambiguously. We show that in both cases (unidirectional or oppositely directed actions of toxicants) the signs of the model coefficients b1, b2 and b12, in conjunction with the coordinates of the saddle point S help unambiguously identify the type of combined action by comparing the observed effect with the zero interaction response surface. An atlas of all possibly combined action types for two toxicants for the hyperbolic paraboloid model was created. Applications of the developed formalism to experimental data are provided. PMID- 26894919 TI - Widespread colocalization of the Drosophila histone acetyltransferase homolog MYST5 with DREF and insulator proteins at active genes. AB - MYST family histone acetyltransferases play important roles in gene regulation. Here, we have characterized the Drosophila MYST histone acetyltransferase (HAT) encoded by cg1894, whose closest homolog is Drosophila MOF, and which we have termed MYST5. We found it localized to a large number of interbands as well as to the telomeres of polytene chromosomes, and it showed strong colocalization with the interband protein Z4/Putzig and RNA polymerase II. Accordingly, genome-wide location analysis by ChIP-seq showed co-occurrence of MYST5 with the Z4 interacting partner Chriz/Chromator. Interestingly, MYST5 bound to the promoter of actively transcribed genes, and about half of MYST5 sites colocalized with the transcription factor DNA replication-related element-binding factor (DREF), indicating a role for MYST5 in gene expression. Moreover, we observed substantial overlap of MYST5 binding with that of the insulator proteins CP190, dCTCF, and BEAF-32, which mediate the organization of the genome into functionally distinct topological domains. Altogether, our data suggest a broad role for MYST5 both in gene-specific transcriptional regulation and in the organization of the genome into chromatin domains, with the two roles possibly being functionally interconnected. PMID- 26894920 TI - Cognitive Function and White Matter Changes Associated with Renal Transplantation. AB - BACKGROUND: End-stage renal disease (ESRD) is a disease with an aging population and a high prevalence of cognitive impairment affecting quality of life, health care costs and mortality. Structural changes in the brain with decreased white matter integrity have been observed in ESRD. Understanding the changes in cognition and associated changes in brain structure after renal transplantation can help define the mechanisms underlying cognitive impairment in ESRD. METHODS: We conducted a prospective, observational cohort study in ESRD patients listed for renal transplantation and followed them post-transplantation. We assessed their cognitive function with a battery of neuropsychological tests and brain white matter integrity with diffusion tensor imaging (DTI) both before transplant and 3 months after transplant. RESULTS: Eleven patients, aged 56.5 +/- 10.7 years, completed the study. Cognitive measures of memory and executive function improved after the transplant, specifically on tests of logical memory I (p = 0.004), logical memory II (p = 0.003) and digit symbol (p < 0.0001). DTI metrics also improved post the transplant with an increase in fractional anisotropy (p = 0.01) and decrease in mean diffusivity (p = 0.004). These changes were more prominent in tracts associated with memory and executive function. CONCLUSIONS: Cognitive function, particularly memory and executive function, improve post the transplant with concurrent improvements in white matter integrity in tracts associated with memory and executive function. These data suggest that abnormalities in cognition and brain structure seen in the ESRD population are at least partially reversible. PMID- 26894922 TI - Prospective Study on Music Therapy in Terminally Ill Cancer Patients during Specialized Inpatient Palliative Care. AB - OBJECTIVE: This study was a prospective evaluation of feasibility, acceptance, and potential beneficial effects of music therapy in terminally ill cancer patients on a specialized palliative care inpatient ward. METHODS: Intervention had to consist of at least two sessions, but frequency and duration was left to the patients' decision. Different music therapy methods were offered to the patient at the beginning of every session. Patients rated their subjective benefit. Disease-related and sociodemographic factors were considered as potentially influencing factors. RESULTS: A total of 166 music therapy sessions were performed with 41 patients (average, 4; range, 2-10). Average session duration was 41 minutes (range, 20-70). Most favored methods were therapeutic conversation in 84% of sessions; listening to relaxing music, 39%; playing an instrument, 31%; and music-lead imagination, 11%. Receptive music therapy was applied in 45%, active forms in 25%, a combination of both in 7%, and therapeutic conversation only in 23%. Music therapy was rated to be "helpful" in 68%. Positive effects were significantly associated with frequency (p = 0.009) and duration (p = 0.040), living in a partnership (p = 0.017), having children (p = 0.035), psycho-oncologic therapy (p = 0.043), experience with music therapy (p = 0.007), role of music in life (p = 0.035), playing an instrument (p = 0.021), and singing regularly (p = 0.003). CONCLUSION: Music therapy techniques, especially receptive methods, are feasible and well accepted in terminally ill cancer patients. Therapeutic conversation seems to play an important role. Frequency and duration of music therapy, previous experience with music and music therapy, as well as sociodemographic factors influence positive effects of music therapy. PMID- 26894923 TI - Synthesis and Isomeric Effects of Ladder-Type Alkylated Terbenzodithiophene Derivatives. AB - A new class of heptacyclic ladder-type terbenzodithiophene (TBDT) structures merging three fused benzodithophenes was developed. Two TBDT conjugated isomers, named as syn-TBDT and anti-TBDT, where the two thienyl rings in the outmost BDT units are in the syn- and anti-fashion, are designed. Two decyl groups are introduced to their 6,13 and 7,14-positions to form four isomeric 6,13-syn-TBDT, 7,14-syn-TBDT, 6,13-anti-TBDT, and 7,14-anti-TBDT structures which are constructed by the DBU-induced 6-benzannulation involving propargyl-allenyl isomerization of the dieneyne moieties in the corresponding precursors followed by 6pi-electrocyclization/aromatization, while isomeric TD-syn-TBDT and TD-anti TBDT with four decyl groups substituted at 6,7,13,14-positions are synthesized via palladium-catalyzed dialkylacetylene insertion/C-H arylation of the corresponding iodobiaryl precursors. The intrinsic properties can be modulated by molecular manipulation of the main-chain and side-chain isomeric structures. anti TBDT derivatives exhibit higher melting points, larger bandgaps, stronger intermolecular interactions, and higher mobility than the corresponding syn-TBDT analogues. These molecules can be further utilized as building blocks to make various TBDT-based materials for optoelectronic applications. PMID- 26894921 TI - Niacin Skin Sensitivity Is Increased in Adolescents at Ultra-High Risk for Psychosis. AB - BACKGROUND: Most studies provide evidence that the skin flush response to nicotinic acid (niacin) stimulation is impaired in schizophrenia. However, only little is known about niacin sensitivity in the ultra-high risk (UHR) phase of psychotic disorders. METHODS: We compared visual ratings of niacin sensitivity between adolescents at UHR for psychosis according to the one year transition outcome (UHR-T n = 11; UHR-NT n = 55) with healthy controls (HC n = 25) and first episode schizophrenia patients (FEP n = 25) treated with atypical antipsychotics. RESULTS: Contrary to our hypothesis niacin sensitivity of the entire UHR group was not attenuated, but significantly increased compared to the HC group, whereas no difference could be found between the UHR-T and UHR-NT groups. As expected, niacin sensitivity of FEP was attenuated compared to HC group. In UHR individuals niacin sensitivity was inversely correlated with omega-6 and -9 fatty acids (FA), but positively correlated with phospholipase A2 (inPLA2) activity, a marker of membrane lipid repair/remodelling. CONCLUSIONS: Increased niacin sensitivity in UHR states likely indicates an impaired balance of eicosanoids and omega-6/-9 FA at a membrane level. Our findings suggest that the emergence of psychosis is associated with an increased mobilisation of eicosanoids prior to the transition to psychosis possibly reflecting a "pro-inflammatory state", whereas thereafter eicosanoid mobilisation seems to be attenuated. Potential treatment implications for the UHR state should be further investigated. PMID- 26894924 TI - The effect of dapagliflozin on renal function in patients with type 2 diabetes. AB - BACKGROUND: Dapagliflozin's antihyperglycemic effects are mediated by inhibition of renal sodium-glucose cotransporter-2; therefore, renal safety of dapagliflozin was assessed. METHODS: Twelve double-blind, placebo-controlled, randomized clinical trials were analyzed up to 24 weeks (N = 4545). Six of the 12 studies included long-term data for up to 102 weeks (N = 3036). Patients with type 2 diabetes with normal or mildly impaired renal function [estimated glomerular filtration rate (eGFR) 60 to <90 mL/min/1.73 m(2)] were treated with dapagliflozin (2.5, 5, or 10 mg/day) or placebo. Renal adverse events (AEs) were assessed. RESULTS: Mean eGFR showed small transient reductions with dapagliflozin at week 1, but returned to near baseline values by week 24 and remained stable to week 102. Mean eGFR changes were not very different for dapagliflozin 2.5, 5 and 10 mg versus placebo at 102 weeks: -0.74, 2.52 and 1.38 versus 1.31 mL/min/1.73 m(2), respectively. Renal AEs were similar in frequency to placebo through 24 weeks (1.4, 1.3, 0.9, and 0.9 %, respectively) and 102 weeks (2.4, 1.8, 1.9 and 1.7 %, respectively). Few were serious (0.2, 0.1, 0 and 0.3 %, respectively, over 102 weeks). The most common renal event was serum creatinine increase. In sub group analyses in patients >=65 years of age or those with moderate renal impairment (eGFR 30 to <60 mL/min/1.73 m(2)), renal AEs occurred more frequently with dapagliflozin than placebo. No events of acute tubular necrosis were reported. CONCLUSION: In patients with normal or mildly impaired renal function, dapagliflozin is not associated with increased risk of acute renal toxicity or deterioration of renal function. All trials included in this analysis are registered at ClinicalTrials.gov: NCT00263276, NCT00972244, NCT00528372, NCT00736879, NCT00528879, NCT00855166, NCT00357370, NCT00680745, NCT00683878, NCT00673231, NCT00643851, NCT00859898. PMID- 26894926 TI - Tubo-Ovarian Abscess (with/without Pseudotumor Area) Mimicking Ovarian Malignancy: Role of Diffusion-Weighted MR Imaging with Apparent Diffusion Coefficient Values. AB - OBJECTIVE: To assess the added value of diffusion-weighted magnetic resonance imaging (DWI) with apparent diffusion coefficient (ADC) values compared to MRI, for characterizing the tubo-ovarian abscesses (TOA) mimicking ovarian malignancy. MATERIALS AND METHODS: Patients with TOA (or ovarian abscess alone; n = 34) or ovarian malignancy (n = 35) who underwent DWI and MRI were retrospectively reviewed. The signal intensity of cystic and solid component of TOAs and ovarian malignant tumors on DWI and the corresponding ADC values were evaluated, as well as clinical characteristics, morphological features, MRI findings were comparatively analyzed. Receiver operating characteristic (ROC) curve analysis based on logistic regression was applied to identify different imaging characteristics between the two patient groups and assess the predictive value of combination diagnosis with area under the curve (AUC) analysis. RESULTS: The mean ADC value of the cystic component in TOA was significantly lower than in malignant tumors (1.04 +/- 0 .41 * 10(-3) mm(2)/s vs. 2.42 +/- 0.38 * 10(-3) mm(2)/s; p < 0.001). The mean ADC value of the enhanced solid component in 26 TOAs was 1.43 +/- 0.16*10(-3) mm(2)/s, and 46.2% (12 TOAs; pseudotumor areas) showed significantly higher signal intensity on DW-MRI than in ovarian malignancy (mean ADC value 1.44 +/- 0.20*10(-3) mm(2)/s vs.1.18 +/- 0.36 * 10(-3) mm(2)/s; p = 0.043). The combination diagnosis of ADC value and dilated tubal structure achieved the best AUC of 0.996. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of MRI vs. DWI with ADC values for predicting TOA were 47.1%, 91.4%, 84.2%, 64%, and 69.6% vs. 100%, 97.1%, 97.1%, 100%, and 98.6%, respectively. CONCLUSIONS: DW-MRI is superior to MRI in the assessment of TOA mimicking ovarian malignancy, and the ADC values aid in discriminating the pseudotumor area of TOA from the solid portion of ovarian malignancy. PMID- 26894925 TI - Type D Personality Predicts Poor Medication Adherence in Chinese Patients with Type 2 Diabetes Mellitus: A Six-Month Follow-Up Study. AB - BACKGROUND: Type D personality and medication nonadherence have been shown to be associated with poor health outcomes. Type D personality is associated with poor medication adherence in patients with coronary artery disease, myocardial infarction, and heart failure. However, the relationship between type D personality and medication adherence in patients with Type 2 Diabetes Mellitus (T2DM) remains unknown. This study aims to examine whether type D personality was associated with medication adherence in patients with T2DM. DESIGN AND SETTINGS: A follow-up study was conducted in general hospital of the People's Liberation Army in Beijing. METHODS: 412 T2DM patients (205 females), who were recruited by circular systematic random sampling, provided demographic and baseline data about medical information and completed measures of Type D personality. Then, 330 patients went on to complete a self-report measure of medication adherence at the sixth month after baseline data collection. Chi-square test, t tests, and hierarchical multiple regression analyses were conducted, as needed. RESULTS: Patients with type D personality were significantly more likely to have poor medication adherence (p<0.001). Type D personality predicts poor medication adherence before and after controlling for covariates when it was analyzed as a categorical variable. However, the dimensional construct of type D personality was not associated with medication adherence when analyzed as a continuous variable. CONCLUSION: Although, as a dimensional construct, type D personality may not reflect the components of the personality associated with poor medication adherence in patients with T2DM, screening for type D personality may help to identify those who are at higher risk of poor medication adherence. Interventions, aiming to improve medication adherence, should be launched for these high-risk patients. PMID- 26894928 TI - Phase transition kinetics and surface binding states of methylammonium lead iodide perovskite. AB - We have presented a detailed analysis of the phase transition kinetics and binding energy states of solution processed methylammonium lead iodide (MAPbI3) thin films prepared at ambient conditions and annealed at different elevated temperatures. It is the processing temperature and environmental conditions that predominantly control the crystal structure and surface morphology of MAPbI3 thin films. The structural transformation from tetragonal to cubic occurs at 60 degrees C with a 30 minute annealing time while the 10 minute annealed films posses a tetragonal crystal structure. The transformed phase is greatly intact even at the higher annealing temperature of 150 degrees C and after a time of 2 hours. The charge transfer interaction between the Pb 4f and I 3d oxidation states is quantified using XPS. PMID- 26894927 TI - Deltex1 Polymorphisms Are Associated with Hepatitis B Vaccination Non-Response in Southwest China. AB - BACKGROUND: Hepatitis B vaccination is the most important tool available for preventing hepatitis B virus (HBV) infection and reducing the prevalence of infection. However, epidemiological studies have demonstrated that morethan 5% of patients exhibit a non- or hypo-response to the HBV vaccine. Genetic variations associated with T cell immunity contribute to the immune response to HBV vaccination. The deltex 1 (DTX1) gene is involved in T cell anergy, which may also be associated with the immune response to the HBV vaccination. METHODS: We detected 10 single nucleotide polymorphisms (SNPs) in or around the DTX1 gene in 601 infants out of a population from Southwest China, including 299 high responders(HRs; HBsAb > 100 mIU/mL) and 302 non-responders (NRs; HBsAb < 10 mIU/mL). An additional validation study was performed, comprising 230 adult patients(135 HRs and 95 NRs) from Southwest China. RESULTS: This study found that the minor allele 'G' of rs2384077 (adjusted p = 2.63E(-04)), and the minor allele 'C' of rs10744794 (adjusted p = 3.69E(-04)) in the first intron of the DTX1 gene were remarkably associated with the immune response to HBV vaccination in both infant and adult populations. Moreover, a subsequent analysis indicated that haplotypes (A-T, G-C) of the two SNPs were significantly associated with the immune response to HBV vaccination. CONCLUSIONS: Two SNPs (rs2384077 and rs10744794) in an intron of DTX1 and the linkage disequilibrium (LD) block are significantly associated with the immune response to HBV vaccination. The functional element annotation of the LD block between the two SNPs contains four transcriptional regulatory elements. The results suggest that these two SNPs may be involved in the immune response to HBV vaccination. PMID- 26894930 TI - Self-perceived vision in farming, forestry, and fishing occupations. AB - Using data from the 2005-2006 and 2007-2008 NHANES questionnaires, we evaluated self-perceived vision difficulty in individuals with a history of farming, forestry, and fishing (FFF) occupations. A self-perceived vision difficulty indicator was derived from responses to 3 separate measures. Those indicating farming, forestry, or fishing as longest job worked were classified as having an FFF history and compared to those reporting any other occupation. Logistic regression analyses utilizing NHANES sampling weights were conducted. After controlling for age, gender, race/ethnicity, education, and income-to-poverty ratio, those with an FFF history were 76% more likely to report vision difficulty than those having an alternate occupational history. Personal protective equipment and routine optometric examination may be particularly prudent for this occupational group. PMID- 26894929 TI - Serum Ferritin, Weight Gain, Disruptive Behavior, and Extrapyramidal Symptoms in Risperidone-Treated Youth. AB - BACKGROUND: Iron deficiency disrupts dopaminergic signaling in rodents, resulting in cognitive deficits that may be reversed with psychostimulants. In humans, iron deficiency with or without anemia has similarly been found to cause neuropsychological and behavioral impairments. However, the clinical effects of low body iron stores in antipsychotic-treated children have not been examined. METHODS: Medically healthy, 5- to 17-year-old boys treated with risperidone for at least 1 year were enrolled between February 2009 and November 2013 in a multiphase study, examining the skeletal effects of calcium and vitamin D supplementation in risperidone-induced hyperprolactinemia. Anthropometric measures were collected and medical and pharmacy records were reviewed to obtain treatment history. Psychiatric diagnoses were based on clinical interviews, structured interviews, rating scales, and a review of their medical records. Extrapyramidal symptoms were assessed, and a food frequency questionnaire was completed in a subsample. Laboratory tests, including ferritin concentration (a marker of body iron status), were obtained upon study entry. RESULTS: A total of 114 participants (mean age: 11.0 +/- 2.6 years) were included, the vast majority (>90%) having attention-deficit/hyperactivity disorder and/or disruptive behavior disorder. They had taken risperidone for an average 3.1 +/- 2.0 years. Their serum ferritin concentration was 37.3 +/- 25.6 MUg/L with 21% of the sample having a level <20 MUg/L, despite appropriate daily dietary iron intake. Ferritin concentration was inversely associated with weight gain following risperidone treatment onset but was not significantly associated with prolactin. After adjusting for the weight-adjusted dose of psychostimulants and risperidone and the daily dose of selective serotonin reuptake inhibitors, ferritin was inversely associated with the severity of disruptive behavior and positively associated (albeit marginally) with prosocial behavior. No association was found between ferritin concentration and extrapyramidal symptoms. CONCLUSIONS: Body iron stores are inversely related to risperidone-induced weight gain, even after extended treatment and despite adequate iron intake. Low iron stores are associated with poorer treatment response. Future research should examine iron absorption during antipsychotic treatment and whether repleting iron stores would facilitate clinical response. PMID- 26894931 TI - Cyclophosphamide treatment-induced leukopenia rates in ANCA-associated vasculitis are influenced by variant CYP450 2C9 genotypes. AB - AIM: Correlation of outcomes of cyclophosphamide (CP) therapy in antineutrophil cytoplasmic antibody-associated vasculitis with genotype polymorphisms in prodrug activating cytochrome P450 enzyme genes CYP2C9 and CYP2C19. PATIENTS & METHODS: One hundred and ninety six patients with antineutrophil cytoplasmic antibody associated vasculitis treated with CP, either as intravenous pulse or as daily oral medication, were included. Genotypes of CYP2C9 and CYP2C19 were correlated with clinical outcomes (leukopenia, infection, urotoxicity and treatment response). RESULTS: Sixty five (33.2%) patients had variant CYP2C9 and 55 (28.1%) had variant CYP2C19 genotype. In patients bearing variant CYP2C9, leukopenia was documented significantly more frequent than in carriers of wild-type CYP2C9 (55.4 vs 37.4%; odds ratio: 2.08; 95% CI: 1.14-3.80; p = 0.017). The impact of the CYP2C9 genotype was stronger in patients treated with oral CP (69.6 vs 45.6%; odds ratio: 2.73; 95% CI: 1.27-5.89; p = 0.009), but was not present in patients treated with intravenous pulsed CP. We observed less refractory disease courses in patients with variant CYP2C9, not reaching statistical significance. CONCLUSION: Patients with variant CYP2C9 are at increased risk for cyclophosphamide-induced leukopenia but may have a better chance to respond to treatment. PMID- 26894932 TI - Leaf Dynamics of Panicum maximum under Future Climatic Changes. AB - Panicum maximum Jacq. 'Mombaca' (C4) was grown in field conditions with sufficient water and nutrients to examine the effects of warming and elevated CO2 concentrations during the winter. Plants were exposed to either the ambient temperature and regular atmospheric CO2 (Control); elevated CO2 (600 ppm, eC); canopy warming (+2 degrees C above regular canopy temperature, eT); or elevated CO2 and canopy warming (eC+eT). The temperatures and CO2 in the field were controlled by temperature free-air controlled enhancement (T-FACE) and mini free air CO2 enrichment (miniFACE) facilities. The most green, expanding, and expanded leaves and the highest leaf appearance rate (LAR, leaves day(-1)) and leaf elongation rate (LER, cm day(-1)) were observed under eT. Leaf area and leaf biomass were higher in the eT and eC+eT treatments. The higher LER and LAR without significant differences in the number of senescent leaves could explain why tillers had higher foliage area and leaf biomass in the eT treatment. The eC treatment had the lowest LER and the fewest expanded and green leaves, similar to Control. The inhibitory effect of eC on foliage development in winter was indicated by the fewer green, expanded, and expanding leaves under eC+eT than eT. The stimulatory and inhibitory effects of the eT and eC treatments, respectively, on foliage raised and lowered, respectively, the foliar nitrogen concentration. The inhibition of foliage by eC was confirmed by the eC treatment having the lowest leaf/stem biomass ratio and by the change in leaf biomass-area relationships from linear or exponential growth to rectangular hyperbolic growth under eC. Besides, eC+eT had a synergist effect, speeding up leaf maturation. Therefore, with sufficient water and nutrients in winter, the inhibitory effect of elevated CO2 on foliage could be partially offset by elevated temperatures and relatively high P. maximum foliage production could be achieved under future climatic change. PMID- 26894933 TI - Concentrated Solutions of Single-Chain Nanoparticles: A Simple Model for Intrinsically Disordered Proteins under Crowding Conditions. AB - By means of large-scale computer simulations and small-angle neutron scattering (SANS), we investigate solutions of single-chain nanoparticles (SCNPs), covering the whole concentration range from infinite dilution to melt density. The analysis of the conformational properties of the SCNPs reveals that these synthetic nano-objects share basic ingredients with intrinsically disordered proteins (IDPs), as topological polydispersity, generally sparse conformations, and locally compact domains. We investigate the role of the architecture of the SCNPs in their collapse behavior under macromolecular crowding. Unlike in the case of linear macromolecules, which experience the usual transition from self avoiding to Gaussian random-walk conformations, crowding leads to collapsed conformations of SCNPs resembling those of crumpled globules. This behavior is already found at volume fractions (about 30%) that are characteristic of crowding in cellular environments. The simulation results are confirmed by the SANS experiments. Our results for SCNPs--a model system free of specific interactions- propose a general scenario for the effect of steric crowding on IDPs: collapse from sparse conformations at high dilution to crumpled globular conformations in cell environments. PMID- 26894934 TI - Structural phase diagram for ultra-thin epitaxial Fe3O4 / MgO(0 0 1) films: thickness and oxygen pressure dependence. AB - A systematic investigation of the thickness and oxygen pressure dependence for the structural properties of ultra-thin epitaxial magnetite (Fe3O4) films has been carried out; for such films, the structural properties generally differ from those for the bulk when the thickness ?10 nm. Iron oxide ultra-thin films with thicknesses varying from 3 nm to 20 nm were grown on MgO (0 0 1) substrates using molecular beam epitaxy under different oxygen pressures ranging from 1 * 10(-7) torr to 1 * 10(-5) torr. The crystallographic and electronic structures of the films were characterized using low energy electron diffraction (LEED) and x-ray photoemission spectroscopy (XPS), respectively. The quality of the epitaxial Fe3O4 ultra-thin films was judged by magnetic measurements of the Verwey transition, along with complementary XPS spectra. It was observed that under the same growth conditions the stoichiometry of ultra-thin films under 10 nm transforms from the Fe3O4 phase to the FeO phase. In this work, a phase diagram based on thickness and oxygen pressure has been constructed to explain the structural phase transformation. It was found that high-quality magnetite films with thicknesses ?20 nm formed within a narrow range of oxygen pressure. An optimal and controlled growth process is a crucial requirement for the accurate study of the magnetic and electronic properties for ultra-thin Fe3O4 films. Furthermore, these results are significant because they may indicate a general trend in the growth of other oxide films, which has not been previously observed or considered. PMID- 26894936 TI - Letter From the Editor. PMID- 26894935 TI - Naproxen, a Nonsteroidal Anti-Inflammatory Drug, Can Affect Daily Hypobaric Hypoxia-Induced Alterations of Monoamine Levels in Different Areas of the Brain in Male Rats. AB - Goswami, Ananda Raj, Goutam Dutta, and Tusharkanti Ghosh. Naproxen, a nonsteroidal anti-inflammatory drug can affect daily hypobaric hypoxia-induced alterations of monoamine levels in different areas of the brain in male rats. High Alt Med Biol. 17:133-140, 2016.-The oxidative stress (OS)-induced prostaglandin (PG) release, in hypobaric hypoxic (HHc) condition, may be linked with the changes of brain monoamines. The present study intends to explore the changes of monoamines in hypothalamus (H), cerebral cortex (CC), and cerebellum (CB) along with the motor activity in rats after exposing them to simulated hypobaric condition and the role of PGs on the daily hypobaric hypoxia (DHH) induced alteration of brain monoamines by administering, an inhibitor of PG synthesis, naproxen. The rats were exposed to a decompression chamber at 18,000 ft for 8 hours per day for 6 days after administration of vehicle or naproxen (18 mg/kg body wt.). The monoamine levels (epinephrine, E; norepinephrine, NE; dopamine, DA; and 5-hydroxytryptamine, 5-HT) in CC, CB, and H were assayed by high-performance liquid chromatography (HPLC) with electrochemical detection, and the locomotor behavior was measured by open field test. The NE and DA levels were decreased in CC, CB, and H of the rat brain in HHc condition. The E and 5-HT levels were decreased in CC, but in H and CB, they remained unaltered in HHc condition. These DHH-induced changes of monoamines in brain areas were prevented after administration of naproxen in HHc condition. The locomotor behavior remained unaltered in HHc condition and after administration of naproxen in HHc condition. The DHH-induced changes of monoamines in the brain in HHc condition are probably linked with PGs that may be induced by OS. PMID- 26894937 TI - Expression of PTEN and beta-Catenin and Their Relationship With Clinicopathological and Prognostic Factors in Endometrioid Type Endometrial Cancer. AB - OBJECTIVE: The aim of this study was to investigate rates of expression of PTEN (phosphatase and tensin homolog deleted on chromosome 10) and beta-catenin and their relationship with clinicopathological and prognostic factors in endometrioid type endometrial cancer (EC). METHODS AND MATERIALS: PTEN and beta catenin expressions of 59 operated patients with EC between January 2000 and December 2008 and followed-up until December 2014 in Cerrahpasa School of Medicine, Gynecologic Oncology Division, were evaluated retrospectively. Clinical data were obtained from patient files, and pathological data were obtained from pathology records. Each patient had 4 paraffin sections of tumoral tissue. These sections were stained by immunohistochemical methods. Clinical features and postoperative histopathologic findings were analyzed using Fisher exact test or the chi(2) test as appropriate. The Kaplan-Meier method was used to generate the survival curves. RESULTS: During median follow-up of 102 months, tumor recurrence and disease-related mortality were observed in 10 (16.9%) and 7 (11.9%) cases, respectively. Immunohistochemical staining of PTEN and beta-catenin were positive in 61% and 69.5% of all cases, respectively. Positive staining of PTEN was positively correlated with myometrial invasion (P= 0.02). There was no correlation between beta-catenin and clinicopathological factors. PTEN or beta catenin positivity were not significant prognostic factors for 5-year overall survival (P = 0.37, P = 0.62, respectively) and 5-year disease-free survival (P = 0.28, P = 0.58, respectively). CONCLUSIONS: PTEN and beta-catenin expressions cannot be used to determine prognosis in patients with EC as PTEN and beta catenin staining status were found to have no significant effect on 5-year overall survival and disease-free survival. Positive staining of PTEN may be associated with increased myometrial invasion. Meta-analyses and broader studies are needed to evaluate the prognostic value of PTEN and beta-catenin in EC. PMID- 26894938 TI - Should Groin Recurrence Still Be Considered as a Palliative Situation in Vulvar Cancer Patients?: A Brief Report. AB - OBJECTIVE: To assess survival after groin recurrence in patients with vulvar cancer in the transition period of the implementation of the sentinel lymph node biopsy procedure. Recurrence of groin metastases in vulvar cancer patients is assumed to be lethal. It is unknown if early detection of relapse and multimodal treatment strategies improve the outcome of patients with groin recurrence. METHODS: Multicenter retrospective cohort study of patients with recurrent vulvar cancer who presented with groin and/or pelvic lymph node metastases between 2000 and 2014 at 3 tertiary referral hospitals. Our primary outcome was to assess survival after groin recurrence of vulvar cancer and the influence of multimodal treatment. All analyses were done using Stata 12 (Stata Corporation, College Station, Tex). Hazard ratios (HRs) and their corresponding 95% confidence intervals were calculated using a Cox proportional hazards model. RESULTS: We identified 30 patients with a median time from diagnosis to groin recurrence of 10 months. The median follow-up of patients who were alive at the time of analysis was 22 months (range, 9-123 months). A Kaplan-Meier estimate showed an overall survival rate of 50% after 7 years. Patients with multimodal groin relapse treatment performed better than those with single-mode treatment (HR, 0.25; P = 0.037). Lymph node metastases at diagnosis were also associated with lower survival (HR, 6.11; P = 0.020). We observed a trend toward lower survival with a tumor size greater than T1 (HR, 2.55; P = 0.111). The time from diagnosis to groin recurrence had no influence on survival (HR, 0.99; P = 0.561). CONCLUSIONS: Close follow-up visits for at least 2 years are important to detect recurrent disease in groin and pelvic lymph nodes. Treatment of recurrent groin metastases should no longer be considered as a palliative situation--given that one half of the patients will have long-term survival after multimodal treatment strategies. PMID- 26894939 TI - A series of new lanthanide fumarates displaying three types of 3-D frameworks. AB - A series of lanthanide fumarates [Sm2(fum)3(H2fum)(H2O)2] (1, H2fum = fumaric acid), [Ln2(fum)3-(H2O)4].3H2O {Ln = Tb (2a), Dy (2b)} and [Ln2(fum)3(H2O)4] {Ln = Y (3a), Ho (3b), Er (3c), Tm (3d)} were prepared by the hydrothermal method and their structures were classified into three types. The 3-D framework of compound 1 contains a 1-D infinite [Sm-O-Sm]n chain built up from the connection of SmO8(H2O) polyhedra sharing edges via three -COO group bridges of fumarate ligands, which is further constructed into a 3-D network structure with three kinds of fumarate ligands. Compounds 2a-b are isostructural and consist of a 3-D porous framework with 0-D cavities for the accommodation of chair-like hexameric (H2O)6 clusters. Compounds 3a-d are isostructural and have a 3-D network structure remarkably different from those of 1 and 2a-b, due to the different coordination numbers for the Ln(3+) ions and distinct fumarate ligand bridging patterns. A systematic investigation of seven lanthanide fumarates and five reported compounds revealed that the well-known lanthanide contraction has a significant influence on the formation of lanthanide fumarates. The magnetic properties of compounds 1, 2b and 3b-3d were also investigated. PMID- 26894940 TI - Double-Shelled Nanocages with Cobalt Hydroxide Inner Shell and Layered Double Hydroxides Outer Shell as High-Efficiency Polysulfide Mediator for Lithium-Sulfur Batteries. AB - Lithium-sulfur (Li-S) batteries have been considered as a promising candidate for next-generation electrochemical energy-storage technologies because of their overwhelming advantages in energy density. Suppression of the polysulfide dissolution while maintaining a high sulfur utilization is the main challenge for Li-S batteries. Here, we have designed and synthesized double-shelled nanocages with two shells of cobalt hydroxide and layered double hydroxides (CH@LDH) as a conceptually new sulfur host for Li-S batteries. Specifically, the hollow CH@LDH polyhedra with complex shell structures not only maximize the advantages of hollow nanostructures for encapsulating a high content of sulfur (75 wt %), but also provide sufficient self-functionalized surfaces for chemically bonding with polysulfides to suppress their outward dissolution. When evaluated as cathode material for Li-S batteries, the CH@LDH/S composite shows a significantly improved electrochemical performance. PMID- 26894942 TI - Trigonal-Bipyramidal Coordination in First Ammoniates of ZnF2: ZnF2(NH3)3 and ZnF2(NH3)2. AB - Single crystals of ZnF2(NH3)3 and ZnF2(NH3)2 were obtained under ammonothermal conditions (250 degrees C, 196 MPa and 500 degrees C, 136 MPa). Upon thermal decomposition of both ZnF2(NH3)3 and ZnF2(NH3)2, a microcrystalline powder of ZnF2(NH3) was obtained. ZnF2(NH3)3 and ZnF2(NH3)2 represent probable intermediates in a conceivable ammonothermal synthesis of the semiconductor Zn3N2 and manifest a rare trigonal-bipyramidal coordination of F(-) and NH3 ligands around Zn(2+) according to single-crystal X-ray diffraction. Thermal analysis of all three compounds showed not only ZnF2(NH3) but also ZnF2(NH3)2 to be decomposition intermediates of ZnF2(NH3)3 prior to the formation of ZnF2. All three compounds demonstrate hydrogen bonds, as indicated by the intensities and half-widths of the bands in the vibrational spectra and by short N-H...F distances in the crystal structures of ZnF2(NH3)3 and ZnF2(NH3)2. With ZnF2(NH3)3, ZnF2(NH3)2, and ZnF2(NH3), we present the first ammoniates of ZnF2. PMID- 26894943 TI - The clinical management of lower respiratory tract infections. AB - The 2010 Global Burden of Disease Study reported that lower respiratory tract infections, including pneumonia, are the fourth most common cause of death globally. The etiology of acute bronchitis and asthma exacerbations is mostly viral and the therapy is symptomatic. Management decisions in community acquired pneumonia regarding site of care, extent of assessment, and level of treatment are based primarily on disease severity (outpatient, inpatient, ICU admission). Antibiotics are the main choice of treatment for patients with pneumonia, acute exacerbations (AE) of COPD (including increased sputum purulence and worsening shortness of breath) and AE of non-CF bronchiectasis. Inhaled antibiotics may represent a more optimal approach for the treatment and prevention of AE of non CF bronchiectasis. Approved strategies for the prevention of exacerbations include smoking cessation and rehabilitation programs, drug therapy and vaccination. PMID- 26894941 TI - Double-jeopardy: The joint impact of neighborhood disadvantage and low social cohesion on cumulative risk of disease among African American men and women in the Jackson Heart Study. AB - OBJECTIVES: Few studies have examined the joint impact of neighborhood disadvantage and low social cohesion on health. Moreover, no study has considered the joint impact of these factors on a cumulative disease risk profile among a large sample of African American adults. Using data from the Jackson Heart Study, we examined the extent to which social cohesion modifies the relationship between neighborhood disadvantage and cumulative biological risk (CBR)-a measure of accumulated risk across multiple physiological systems. METHODS: Our analysis included 4408 African American women and men ages 21-85 residing in the Jackson, MS Metropolitan Area. We measured neighborhood disadvantage using a composite score of socioeconomic indicators from the 2000 US Census and social cohesion was assessed using a 5-item validated scale. Standardized z-scores of biomarkers representing cardiovascular, metabolic, inflammatory, and neuroendocrine systems were combined to create a CBR score. We used two-level linear regression models with random intercepts adjusting for socio-demographic and behavioral covariates in the analysis. A three-way interaction term was included to examine whether the relationship between neighborhood disadvantage and CBR differed by levels of social cohesion and gender. RESULTS: The interaction between neighborhood disadvantage, social cohesion and gender was statistically significant (p = 0.05) such that the association between living in a disadvantaged neighborhood and CBR was strongest for men living in neighborhoods with low levels of social cohesion (B = 0.63, SE: 0.32). In gender-specific models, we found a statistically significant interaction between neighborhood disadvantage and social cohesion for men (p = 0.05) but not for women (p = 0.50). CONCLUSION: Neighborhoods characterized by high levels of economic disadvantage and low levels of social cohesion contribute to higher cumulative risk of disease among African American men. This suggests that they may face a unique set of challenges that put them at greater risk in these settings. PMID- 26894944 TI - Life-span exposure to sinusoidal-50 Hz magnetic field and acute low-dose gamma radiation induce carcinogenic effects in Sprague-Dawley rats. AB - Background In 2002 the International Agency for Research on Cancer classified extremely low frequency magnetic fields (ELFMF) as a possible carcinogen on the basis of epidemiological evidence. Experimental bioassays on rats and mice performed up to now on ELFMF alone or in association with known carcinogens have failed to provide conclusive confirmation. Objectives To study the carcinogenic effects of combined exposure to sinusoidal-50 Hz (S-50 Hz) magnetic fields and acute gamma radiation in Sprague-Dawley rats. Methods We studied groups of male and female Sprague-Dawley rats exposed from prenatal life until natural death to 20 or 1000 MUT S-50 Hz MF and also to 0.1 Gy gamma radiation delivered as a single acute exposure at 6 weeks of age. Results The results of the study showed significant carcinogenic effects for the mammary gland in males and females and a significant increased incidence of malignant schwannomas of the heart as well as increased incidence of lymphomas/leukemias in males. Conclusions These results call for a re-evaluation of the safety of non-ionizing radiation. PMID- 26894945 TI - International Physician Assistant Students Could Become "People Without a Country". PMID- 26894946 TI - "Twinning Model" Is a Better Alternative. PMID- 26894947 TI - Relationship Between Physician Assistant Program Length and Physician Assistant National Certifying Examination Pass Rates. AB - PURPOSE: This study was conducted to examine the relationship between physician assistant (PA) educational program length and PA programs' 5-year average Physician Assistant National Certifying Examination (PANCE) first-time pass rates. METHODS: This was a retrospective correlational study that analyzed previously collected data from a nonprobability purposive sample of accredited PA program Web sites. Master's level PA programs (n = 108) in the United States with published average PANCE scores for 5 consecutive classes were included. Provisional and probationary programs were excluded (n = 4). Study data were not normally distributed per the Kolmogorov-Smirnov test, P = .00. RESULTS: There was no relationship between program length and PANCE pass rates, rho (108) = -0.04, P = .68. Further analyses examining a possible relationship between program phase length (didactic and clinical) and PANCE pass rates also demonstrated no differences (rho [107] = -0.05, P = .60 and rho [107] = 0.02, P = .80, respectively). CONCLUSION: The results of this study suggest that shorter length PA programs perform similarly to longer programs in preparing students to pass the PANCE. In light of rapid expansion of PA educational programs, educators may want to consider these findings when planning the length of study for new and established programs. PMID- 26894948 TI - A Comparison of Students' Perceptions of Stress in Parallel Problem-Based and Lecture-Based Curricula. AB - PURPOSE: A 6-year longitudinal study was conducted to compare the perceived stress experienced during a 2-year master's physician assistant program by 5 cohorts of students enrolled in either problem-based learning (PBL) or lecture based learning (LBL) curricular tracks. The association of perceived stress with academic achievement was also assessed. METHODS: Students rated their stress levels on visual analog scales in relation to family obligations, financial concerns, schoolwork, and relocation and overall on 6 occasions throughout the program. A mixed model analysis of variance examined the students' perceived level of stress by curriculum and over time. Regression analysis further examined school work-related stress after controlling for other stressors and possible lag effect of stress from the previous time point. RESULTS: Students reported that overall stress increased throughout the didactic year followed by a decline in the clinical year with statistically significant curricular (PBL versus LBL) and time differences. PBL students also reported significantly more stress resulting from school work than LBL students at some time points. Moreover, when the other measured stressors and possible lag effects were controlled, significant differences between PBL and LBL students' perceived stress related to school work persisted at the 8- and 12-month measurement points. Increased stress in both curricula was associated with higher achievement in overall and individual organ system examination scores. CONCLUSION: Physician assistant programs that embrace a PBL pedagogy to prepare students to think clinically may need to provide students with additional support through the didactic curriculum. PMID- 26894949 TI - Central Application Service for Physician Assistants Ten-Year Data Report, 2002 to 2011. AB - PURPOSE: This study highlights the trends and data points of interest in physician assistant (PA) applicant data over the first 10 years of the Central Application Service for Physician Assistants (CASPA) (2002-2011) and PA matriculant data over the last 5 years of that 10-year period (2007-2011). METHODS: A retrospective study of data provided by applicants to all CASPA participating PA programs between 2002 and 2011 was conducted. Applicant data analyzed over the 10-year period were provided by applicants and collected through an online CASPA applicant portal. Academic information was verified by CASPA staff through official transcript review. Matriculant data were obtained from CASPA-participating programs through the online CASPA admissions portal, which linked to applicant data in the CASPA applicant portal. RESULTS: During the first 10 years of the CASPA service, the Physician Assistant Education Association experienced a 93% increase in the number of CASPA-participating programs and a 255% increase in the number of unique applicants identified through CASPA. Relatively constant trends were identified in the major demographic features (age, gender, ethnic composition, and disadvantaged status) and the academic data of applicants. Major demographic features of matriculants (2007-2011) also remained relatively constant, whereas trends in academic data of matriculants revealed an increasing total grade point average. CONCLUSION: This 10-year comprehensive analysis of the CASPA data will benefit the profession by establishing a baseline of applicant characteristics. Ultimately, these data will help redefine recruitment strategies at program, state, and national levels by providing programs and national organizations with data needed to target applicants not previously included in recruitment activities. PMID- 26894950 TI - Health Policy in Physician Assistant Education: Teaching Considerations and a Model Curriculum. AB - Recognition is growing within the medical academic community that future clinicians will need the tools to understand and influence health policy decisions. With the passage of the Patient Protection and Affordable Care Act of 2010, future clinicians will need not only clinical competence for successful practice but also an understanding of how health systems function. Although the fourth edition of the Accreditation Standards for Physician Assistant Education contains provisions and stipulations for the teaching of health topics in general and health policy specifically, physician assistant (PA) educators retain little consensus regarding either learning objectives or specific rubrics for teaching these important concepts. In this article, we discuss approaches for teaching health policy, delineate useful educational resources for PA faculty, and propose a model curriculum. PMID- 26894951 TI - Efficient Evidence: Strategies for Accessing and Using Medical Evidence Efficiently. PMID- 26894952 TI - Social Accountability of the Physician Assistant: A Fit-for-Purpose Health Workforce. PMID- 26894953 TI - Digital Note-Taking: Discussion of Evidence and Best Practices. AB - Balancing active course engagement and comprehension with producing quality lecture notes is challenging. Although evidence suggests that handwritten note taking may improve comprehension and learning outcomes, many students still self report a preference for digital note-taking and a belief that it is beneficial. Future research is warranted to determine the effects on performance of digitally writing notes. Independent of the methods or software chosen, best practices should be provided to students with information to help them consciously make an educated decision based on the evidence and their personal preference. Optimal note-taking requires self-discipline, focused attention, sufficient working memory, thoughtful rewording, and decreased distractions. Familiarity with the tools and mediums they choose will help students maximize working memory, produce better notes, and aid in their retention of material presented. PMID- 26894954 TI - New dimensions in the use of rodent behavioral tests for novel drug discovery and development. AB - INTRODUCTION: Dimensional models of psychopathology describe mental illness in terms of natural variance along certain phenotypic dimensions that are continuous with normal. Vulnerability to psychopathology might arise when certain adaptive psychophysiological processes, conserved between humans and non-human animals, function outside of their "normal" range. Therefore, an in-depth understanding of the neurobiology and neurochemistry underlying these processes could identify possible novel drug targets. AREAS COVERED: Psychophysiological processes that might be related to anxiety disorders and depression are proposed and discussed. Those processes relevant to depressive disorders include: hedonic responsiveness, biases in the processing of stimuli, and sleep architecture. Those relevant to anxiety disorders include: startle reactivity, CO2 sensitivity, and fear generalization. Rodent behavioral tests for assessing the function of these processes and investigating their neurobiology are described. A psychophysiological process strategy for translational research is proposed, which focusses on understanding the neurobiology and neurochemistry underlying key psychophysiological processes that, when their activity deviates from normal, are associated with neuropsychiatric symptoms. This strategy emphasizes the use of analogous tests and measures in both preclinical and clinical studies, while de-emphasizing the use of preclinical animal models that attempt to replicate features of the neuropsychiatric disorder through experimental manipulations. EXPERT OPINION: Investigating the neurobiology of key psychophysiological processes in rodents should enhance our understanding of the pathophysiology of neuropsychiatric disorders. New drug development could be directed toward developing pharmacological strategies that would normalize the function of these psychophysiological processes. PMID- 26894955 TI - Registered report: Diverse somatic mutation patterns and pathway alterations in human cancers. AB - The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of selected experiments from a number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 2012, were selected on the basis of citations and Altmetric scores (Errington et al., 2014). This Registered Report describes the proposed replication plan of key experiments from "Diverse somatic mutation patterns and pathway alterations in human cancers" by Kan and colleagues published in Nature in 2010 (Kan et al., 2010). The experiments to be replicated are those reported in Figures 3D-F and 4C-F. Kan and colleagues utilized mismatch repair detection (MRD) technology to identify somatic mutations in primary human tumor samples and identified a previously uncharacterized arginine 243 to histidine (R243H) mutation in the G-protein alpha subunit GNAO1 in breast carcinoma tissue. In Figures 3D-F, Kan and colleagues demonstrated that stable expression of mutant GNAO1(R243D) conferred a significant growth advantage in human mammary epithelial cells, confirming the oncogenic potential of this mutation. Similarly, expression of variants with somatic mutations in MAP2K4, a JNK pathway kinase (shown in Figures 4C-E) resulted in a significant increase in anchorage-independent growth. Interestingly, these mutants exhibited reduced kinase activity compared to wild type MAP2K4, indicating these mutations impose a dominant-negative influence to promote growth (Figure 4F). The Reproducibility Project: Cancer Biology is a collaboration between the Center for Open Science and Science Exchange and the results of the replications will be published in eLife. PMID- 26894956 TI - Immune Response: Intracellular pathogens under attack. AB - Antimicrobial proteins deliver a double punch that can destroy the Toxoplasma gondii parasite and its niche inside cells. PMID- 26894957 TI - Immunometabolism: Metabolism fine-tunes macrophage activation. AB - A signaling pathway that rewires metabolism in macrophages to trigger changes in gene expression has been identified. PMID- 26894958 TI - Regulatory consequences of neuronal ELAV-like protein binding to coding and non coding RNAs in human brain. AB - Neuronal ELAV-like (nELAVL) RNA binding proteins have been linked to numerous neurological disorders. We performed crosslinking-immunoprecipitation and RNAseq on human brain, and identified nELAVL binding sites on 8681 transcripts. Using knockout mice and RNAi in human neuroblastoma cells, we showed that nELAVL intronic and 3' UTR binding regulates human RNA splicing and abundance. We validated hundreds of nELAVL targets among which were important neuronal and disease-associated transcripts, including Alzheimer's disease (AD) transcripts. We therefore investigated RNA regulation in AD brain, and observed differential splicing of 150 transcripts, which in some cases correlated with differential nELAVL binding. Unexpectedly, the most significant change of nELAVL binding was evident on non-coding Y RNAs. nELAVL/Y RNA complexes were specifically remodeled in AD and after acute UV stress in neuroblastoma cells. We propose that the increased nELAVL/Y RNA association during stress may lead to nELAVL sequestration, redistribution of nELAVL target binding, and altered neuronal RNA splicing. PMID- 26894961 TI - Multi-source adaptation joint kernel sparse representation for visual classification. AB - Most of the existing domain adaptation learning (DAL) methods relies on a single source domain to learn a classifier with well-generalized performance for the target domain of interest, which may lead to the so-called negative transfer problem. To this end, many multi-source adaptation methods have been proposed. While the advantages of using multi-source domains of information for establishing an adaptation model have been widely recognized, how to boost the robustness of the computational model for multi-source adaptation learning has only recently received attention. To address this issue for achieving enhanced performance, we propose in this paper a novel algorithm called multi-source Adaptation Regularization Joint Kernel Sparse Representation (ARJKSR) for robust visual classification problems. Specifically, ARJKSR jointly represents target dataset by a sparse linear combination of training data of each source domain in some optimal Reproduced Kernel Hilbert Space (RKHS), recovered by simultaneously minimizing the inter-domain distribution discrepancy and maximizing the local consistency, whilst constraining the observations from both target and source domains to share their sparse representations. The optimization problem of ARJKSR can be solved using an efficient alternative direction method. Under the framework ARJKSR, we further learn a robust label prediction matrix for the unlabeled instances of target domain based on the classical graph-based semi supervised learning (GSSL) diagram, into which multiple Laplacian graphs constructed with the ARJKSR are incorporated. The validity of our method is examined by several visual classification problems. Results demonstrate the superiority of our method in comparison to several state-of-the-arts. PMID- 26894959 TI - Binary architecture of the Nav1.2-beta2 signaling complex. AB - To investigate the mechanisms by which beta-subunits influence Nav channel function, we solved the crystal structure of the beta2 extracellular domain at 1.35A. We combined these data with known bacterial Nav channel structural insights and novel functional studies to determine the interactions of specific residues in beta2 with Nav1.2. We identified a flexible loop formed by (72)Cys and (75)Cys, a unique feature among the four beta-subunit isoforms. Moreover, we found that (55)Cys helps to determine the influence of beta2 on Nav1.2 toxin susceptibility. Further mutagenesis combined with the use of spider toxins reveals that (55)Cys forms a disulfide bond with (910)Cys in the Nav1.2 domain II pore loop, thereby suggesting a 1:1 stoichiometry. Our results also provide clues as to which disulfide bonds are formed between adjacent Nav1.2 (912/918)Cys residues. The concepts emerging from this work will help to form a model reflecting the beta-subunit location in a Nav channel complex. PMID- 26894960 TI - Akt-mTORC1 signaling regulates Acly to integrate metabolic input to control of macrophage activation. AB - Macrophage activation/polarization to distinct functional states is critically supported by metabolic shifts. How polarizing signals coordinate metabolic and functional reprogramming, and the potential implications for control of macrophage activation, remains poorly understood. Here we show that IL-4 signaling co-opts the Akt-mTORC1 pathway to regulate Acly, a key enzyme in Ac-CoA synthesis, leading to increased histone acetylation and M2 gene induction. Only a subset of M2 genes is controlled in this way, including those regulating cellular proliferation and chemokine production. Moreover, metabolic signals impinge on the Akt-mTORC1 axis for such control of M2 activation. We propose that Akt-mTORC1 signaling calibrates metabolic state to energetically demanding aspects of M2 activation, which may define a new role for metabolism in supporting macrophage activation. PMID- 26894962 TI - Optical isomers of phenibut inhibit [H(3)]-Gabapentin binding in vitro and show activity in animal models of chronic pain. AB - BACKGROUND: We report that R- and S-phenibut (beta-phenyl-gamma-aminobutyric acid) - derivatives of GABA - bind with an affinity of c.a. 90MUM to the gabapentin binding site in a competitive assay, a value comparable to that for previously claimed targets for this enantioermic molecule. This finding implied potential activity in neuropathic pain, this being one of the clinically validated indications for gabapentin. METHODS: The effect of phenibut on tactile allodynia was tested in a chronic constriction nerve injury (CCI) neuropathic pain model and against hypersensitivity following inflammation induced by inoculation using complete Freund's adjuvant (CFA) model. RESULTS: Indeed, a significant inhibitory effect on tactile allodynia was detected in rats in both employed chronic pain models with stronger and clearly dose dependent effect with R isomer. CONCLUSIONS: The results confirm activity in chronic pain models predicted from affinity for the gabapentin site and suggests, at least partially, that alpha2delta-subunits of presynaptic voltage-gated calcium channels are involved in mediating this effect. PMID- 26894963 TI - Propafenone enhances the anticonvulsant action of classical antiepileptic drugs in the mouse maximal electroshock model. AB - BACKGROUND: Antiarrhythmic and antiepileptic drugs share some mechanisms of actions. Therefore, possibility of interactions between these in epileptic patients with cardiac arrhythmias is quite considerable. Herein, we attempted to assess interactions between propafenone and four conventional antiepileptic drugs: carbamazepine, valproate, phenytoin and phenobarbital. METHODS: Effects of propafenone on seizures were determined in the electroconvulsive threshold test in mice. Interactions between propafenone and antiepileptic drugs were estimated in the model of maximal electroshock. Motor coordination was evaluated in the chimney test, while long-term memory in the passive-avoidance task. Brain concentrations of antiepileptics were determined by fluorescence polarization immunoassay. RESULTS: Propafenone up to 50mg/kg did not affect the electroconvulsive threshold, significantly enhancing this parameter at doses of 60-90mg/kg. Applied at its subthreshold doses, propafenone potentiated the antielectroshock action of all four tested classical antiepileptics: carbamazepine, valproate, phenytoin, and phenobarbital. Propafenone alone and in combinations with antiepileptics impaired neither motor performance nor long-term memory in mice. Propafenone did not change brain concentration of phenytoin and phenobarbital; however, it significantly decreased brain levels of carbamazepine and increased those of valproate. CONCLUSIONS: Propafenone exhibits its own anticonvulsant effect and enhances the action of classical antiepileptic drugs against electrically induced convulsions in mice. Further investigations are required to determine the effect of propafenone on antiepileptic therapy in humans. PMID- 26894964 TI - Cytoprotective mechanism of action of curcumin against cataract. AB - This review discusses the relationship between oxidative stress and cataract formation, molecular mechanism of curcumin action and potential benefits of treatment with the antioxidant curcumin. The first section deals with curcumin and endogenous antioxidants. The second section focuses on the action of curcumin on lipid peroxidation. Calcium homeostasis and curcumin will be discussed in the third section. The fourth section discusses the role of crystallin proteins that are responsible for maintaining lens transparency and the role of curcumin in regulating crystallin expression. The interaction of curcumin with transcription factors will be dealt in the fifth section. The final section will focus on the effect of curcumin on aldose reductase, which is associated with hyperglycemia and cataract. One of the strongest antioxidants is curcumin which has been shown to be very effective against cataract. This compound is better than other antioxidants in preventing cataract but its limited bioavailability can be addressed by employing nanotechnology. PMID- 26894965 TI - Clinical prognostic factors and outcomes of essential thrombocythemia when transformed to myelodysplastic syndromes and acute myeloid leukemia. AB - Transformation of essential thrombocythemia (ET) to myelodysplastic syndromes or acute myeloid leukemia is infrequent, comprising 1-5% of cases with dismal clinical outcome. Studies on prognosis in ET patients with leukemic transformation are limited. The large cohort included 40 patients (1990-2014) with ET transformation (median age of 59 years, M:F of 1:1). Median time from ET diagnosis to transformation was 76 months (26-481) with median follow-up time of 15 years. Advanced age, myelofibrosis (grade 2-3), and leukocytosis at the time of transformation were associated with inferior OS from transformation (p<0.05). Given rarity of the clinical scenario, multicenter efforts are encouraged. PMID- 26894966 TI - Tin Tungstate Nanoparticles: A Photosensitizer for Photodynamic Tumor Therapy. AB - The nanoparticulate inorganic photosensitizer beta-SnWO4 is suggested for photodynamic therapy (PDT) of near-surface tumors via reiterated 5 min blue-light LED illumination. beta-SnWO4 nanoparticles are obtained via water-based synthesis and comprise excellent colloidal stability under physiological conditions and high biocompatibility at low material complexity. Antitumor and antimetastatic effects were investigated with a spontaneously metastasizing (4T1 cells) orthotopic breast cancer BALB/c mouse model. Besides protamine-functionalized beta-SnWO4 (23 mg/kg of body weight, in PBS buffer), chemotherapeutic doxorubicin was used as positive control (2.5 mg/kg of body weight, in PBS buffer) and physiological saline (DPBS) as a negative control. After 21 days, treatment with beta-SnWO4 resulted in a clearly inhibited growth of the primary tumor (all tumor volumes below 3 cm(3)) as compared to the doxorubicin and DPBS control groups (volumes up to 6 cm(3)). Histological evaluations of lymph nodes and lungs as well as the volume of ipsilateral lymph nodes show a remarkable antimetastatic effect being similar to chemotherapeutic doxorubicin but-according to blood counts-at significantly reduced side effects. On the basis of low material complexity, high cytotoxicity under blue-light LED illumination at low dark and long-term toxicity, beta-SnWO4 can be an interesting addition to PDT and the treatment of near-surface tumors, including skin cancer, esophageal/gastric/colon tumors as well as certain types of breast cancer. PMID- 26894968 TI - Extracorporeal support for patients with acute and acute on chronic liver failure. AB - The number of patients developing liver failure; acute on chronic liver failure and acute liver failure continues to increase, along with the demand for donor livers for transplantation. As such there is a clinical need to develop effective extracorporeal devices to support patients with acute liver failure or acute-on chronic liver failure to allow time for hepatocyte regeneration, and so avoiding the need for liver transplantation, or to bridge the patient to liver transplantation, and also potentially to provide symptomatic relief for patients with cirrhosis not suitable for transplantation. Currently devices can be divided into those designed to remove toxins, including plasma exchange, high permeability dialyzers and adsorption columns or membranes, coupled with replacement of plasma proteins; albumin dialysis systems; and bioartificial devices which may provide some of the biological functions of the liver. In the future we expect combinations of these devices in clinical practice, due to the developments in bioartificial scaffolds. PMID- 26894967 TI - Decreased reaction time variability is associated with greater cardiovascular responses to acute stress. AB - Cardiovascular (CV) responses to mental stress are prospectively associated with poor CV outcomes. The association between CV responses to mental stress and reaction times (RTs) in aging individuals may be important but warrants further investigation. The present study assessed RTs to examine associations with CV responses to mental stress in healthy, older individuals using robust regression techniques. Participants were 262 men and women (mean age = 63.3 +/- 5.5 years) from the Whitehall II cohort who completed a RT task (Stroop) and underwent acute mental stress (mirror tracing) to elicit CV responses. Blood pressure, heart rate, and heart rate variability were measured at baseline, during acute stress, and through a 75-min recovery. RT measures were generated from an ex-Gaussian distribution that yielded three predictors: mu-RT, sigma-RT, and tau-RT, the mean, standard deviation, and mean of the exponential component of the normal distribution, respectively. Decreased intraindividual RT variability was marginally associated with greater systolic (B = -.009, SE = .005, p = .09) and diastolic (B = -.004, SE = .002, p = .08) blood pressure reactivity. Decreased intraindividual RT variability was associated with impaired systolic blood pressure recovery (B = -.007, SE = .003, p = .03) and impaired vagal tone (B = .0047, SE = .0024, p = .045). Study findings offer tentative support for an association between RTs and CV responses. Despite small effect sizes and associations not consistent across predictors, these data may point to a link between intrinsic neuronal plasticity and CV responses. PMID- 26894969 TI - Low tristetraprolin expression promotes cell proliferation and predicts poor patients outcome in pancreatic cancer. AB - Tristetraprolin (also known as TTP, TIS11, ZFP36, and Nup475) is a well characterized tumor suppressor that is down-regulated in several tumor types. In the current study, we found that TTP expression was markedly reduced in pancreatic cancer samples as compared to matched normal tissues. Low TTP level was associated with age (P=0.037), tumor size (P=0.008), tumor differentiation (P=0.004), postoperative T stage (pT stage, P<0.001), postoperative N stage (pN stage, P=0.008) and TNM stage (P<0.001). Moreover, low TTP expression predicted reduced survival rates and poor patient outcome. We also found that TTP impairs pancreatic cancer cell proliferation both in vivo and in vitro. Fluorescence Activated Cell Sorting (FACS) assay showed that TTP over-expression both increases apoptosis and decreases proliferation in pancreatic cancer cells. RNA sequencing analysis showed that TTP over-expression downregulates several tumor related factors, including Pim-1 and IL-6. Our findings indicate that TTP could serve as a potential prognostic indicator in pancreatic cancer. PMID- 26894970 TI - Gamabufotalin triggers c-Myc degradation via induction of WWP2 in multiple myeloma cells. AB - Deciding appropriate therapy for multiple myeloma (MM) is challenging because of the occurrence of multiple chromosomal changes and the fatal nature of the disease. In the current study, gamabufotalin (GBT) was isolated from toad venom, and its tumor-specific cytotoxicity was investigated in human MM cells. We found GBT inhibited cell growth and induced apoptosis with the IC50 values <50 nM. Mechanistic studies using functional approaches identified GBT as an inhibitor of c-Myc. Further analysis showed that GBT especially evoked the ubiquitination and degradation of c-Myc protein, thereby globally repressing the expression of c-Myc target genes. GBT treatment inhibited ERK and AKT signals, while stimulating the activation of JNK cascade. An E3 ubiquitin-protein ligase, WWP2, was upregulated following JNK activation and played an important role in c-Myc ubiquitination and degradation through direct protein-protein interaction. The antitumor effect of GBT was validated in a xenograft mouse model and the suppression of MM-induced osteolysis was verified in a SCID-hu model in vivo. Taken together, our study identified the potential of GBT as a promising therapeutic agent in the treatment of MM. PMID- 26894971 TI - Bladder cancer cells secrete while normal bladder cells express but do not secrete AGR2. AB - Anterior gradient 2 (AGR2) is a cancer-associated secreted protein found predominantly in adenocarcinomas. Given its ubiquity in solid tumors, cancer secreted AGR2 could be a useful biomarker in urine or blood for early detection. However, normal organs express and might also secrete AGR2, which would impact its utility as a cancer biomarker. Uniform AGR2 expression is found in the normal bladder urothelium. Little AGR2 is secreted by the urothelial cells as no measurable amounts could be detected in urine. The urinary proteomes of healthy people contain no listing for AGR2. Likewise, the blood proteomes of healthy people also contain no significant peptide counts for AGR2 suggesting little urothelial secretion into capillaries of the lamina propria. Expression of AGR2 is lost in urothelial carcinoma, with only 25% of primary tumors observed to retain AGR2 expression in a cohort of lymph node-positive cases. AGR2 is secreted by the urothelial carcinoma cells as urinary AGR2 was measured in the voided urine of 25% of the cases analyzed in a cohort of cancer vs. non-cancer patients. The fraction of AGR2-positive urine samples was consistent with the fraction of urothelial carcinoma that stained positive for AGR2. Since cancer cells secrete AGR2 while normal cells do not, its measurement in body fluids could be used to indicate tumor presence. Furthermore, AGR2 has also been found on the cell surface of cancer cells. Taken together, secretion and cell surface localization of AGR2 are characteristic of cancer, while expression of AGR2 by itself is not. PMID- 26894972 TI - Parabolic relationship between sex-specific serum high sensitive C reactive protein and non-alcoholic fatty liver disease in Chinese adults: a large population-based study. AB - OBJECTIVES: To evaluate the association between sex-specific serum high sensitive C reactive protein (hsCRP) levels and NAFLD in a large population-based study. RESULTS: From Q1 to Q4, the incidence ratios were 21.1 (95% CI 17.5 24.7), 18.6 (95% CI 16.5 20.8), 24.8 (95% CI 22.4 27.2) and 31.1 (95% CI 28.5 33.6) in males and 6.2 (95% CI 4.4 8.0), 6.0 (95% CI 5.1 7.1), 11.4 (95% CI 9.2 13.7) and 19.5 (95% CI 16.1 22.9) in females. Compared with a 1.7-fold increase (Q4 vs Q2) in males, actuarial incidence increased 3.3-fold (Q4 vs Q2) in females. After adjusting for known confounding variables in this study, in the longitudinal population, compared with the reference group, those in Q1, Q3, and Q4 had HRs of 1.63 (95% CI 1.29-2.05), 1.11 (95% CI 0.93-1.31), 1.14 (95% CI 0.97-1.35) in male and 1.77 (95% CI 1.25-2.49), 1.22 (95% CI 0.93-1.59), 1.36 (95% CI 1.03-1.80) in female for NAFLD, respectively. METHODS: 8618 subjects from Wenzhou Medical Center of Wenzhou People's Hospital were included. Sex specific hsCRP quartiles (Q1 to Q4) were defined: 0-0.1, 0.2-0.4, 0.5-0.8 and 0.9-25.9 for male; 0-0.1, 0.2-0.6, 0.7-1.2 and1.3-28.4 for female. Applying Q2 as reference, Hazard ratios (HRs) and 95% confidence intervals (CIs) for NAFLD were calculated across each quartile of hsCRP. CONCLUSIONS: We report that a sex-specific hsCRP level is independently associated with NAFLD. The association between hsCRP and NAFLD was significantly stronger in females than in males. PMID- 26894973 TI - AMPK and PKA interaction in the regulation of survival of liver cancer cells subjected to glucose starvation. AB - The signaling pathways that govern survival response in hepatic cancer cells subjected to nutritional restriction have not been clarified yet. In this study we showed that liver cancer cells undergoing glucose deprivation both arrested in G0/G1 and died mainly by apoptosis. Treatment with the AMPK activator AICAR phenocopied the effect of glucose deprivation on cell survival, whereas AMPK silencing in HepG2/C3A, HuH-7 or SK-Hep-1 cells blocked the cell cycle arrest and the increase in apoptotic death induced by glucose starvation. Both AMPK and PKA were promptly activated after glucose withdrawal. PKA signaling had a dual role during glucose starvation: whereas it elicited an early decreased in cell viability, it later improved this parameter. We detected AMPK phosphorylation (AMPKalpha(Ser173)) by PKA, which was increased in glucose starved cells and was associated with diminution of AMPK activation. To better explore this inhibitory effect, we constructed a hepatocarcinoma derived cell line which stably expressed an AMPK mutant lacking that PKA phosphorylation site: AMPKalpha1(S173C). Expression of this mutant significantly decreased viability in cells undergoing glucose starvation. Furthermore, after 36 h of glucose deprivation, the index of AMPKalpha1(S173C) apoptotic cells doubled the apoptotic index observed in control cells. Two main remarks arise: 1. AMPK is the central signaling kinase in the scenario of cell cycle arrest and death induced by glucose starvation in hepatic cancer cells; 2. PKA phosphorylation of Ser173 comes out as a strong control point that limits the antitumor effects of AMPK in this situation. PMID- 26894974 TI - Nrf2 is the key to chemotherapy resistance in MCF7 breast cancer cells under hypoxia. AB - Hypoxia leads to reactive oxygen species (ROS) imbalance, which is proposed to associate with drug resistance and oncogenesis. Inhibition of enzymes of antioxidant balancing system in tumor cells was shown to reduce chemoresistance under hypoxia. However, the underlying mechanism remains unknown. The key regulator of antioxidant balancing system is nuclear factor erythroid 2-related factor 2 (NFE2L2, Nrf2). In this study, we showed that hypoxia induced ROS production and increased the Nrf2 activity. Nrf2 activation increased levels of its downstream target antioxidant enzymes, including GCLC and GCLM. The Nrf2 overexpressing also confers chemo-resistant MCF7 cells under normoxia. The in vivo mouse model also demonstrated that the chemical inhibition of Nrf2 can increase cisplatin (CDDP) cytotoxicity. Together, these results showed that Nrf2 serves as a key regulator in chemotherapeutic resistance under hypoxia through ROS-Nrf2-GCLC-GSH pathway. Therefore, targeting Nrf2 can be a potential treatment for hypoxia-induced drug resistance in breast cancer cells. PMID- 26894975 TI - Therapeutic siRNA for drug-resistant HER2-positive breast cancer. AB - HER2 is overexpressed in about 20% of breast cancers and contributes to poor prognosis. Unfortunately, a large fraction of patients have primary or acquired resistance to the HER2-targeted therapy trastuzumab, thus a multi-drug combination is utilized in the clinic, putting significant burden on patients. We systematically identified an optimal HER2 siRNA from 76 potential sequences and demonstrated its utility in overcoming intrinsic and acquired resistance to trastuzumab and lapatinib in 18 HER2-positive cancer cell lines. We provided evidence that the drug-resistant cancer maintains dependence on HER2 for survival. Importantly, cell lines did not readily develop resistance following extended treatment with HER2 siRNA. Using our recently developed nanoparticle platform, systemic delivery of HER2 siRNA to trastuzumab-resistant tumors resulted in significant growth inhibition. Moreover, the optimal HER2 siRNA could also silence an exon 16 skipped HER2 splice variant reported to be highly oncogenic and linked to trastuzumab resistance. PMID- 26894977 TI - PSMB8 and PBK as potential gastric cancer subtype-specific biomarkers associated with prognosis. AB - Gastric adenocarcinoma is a common form of cancer associated with a poor prognosis. We analyzed microarray profiling data from 48 patients with gastric adenocarcinoma to characterize gastric cancer subtypes and identify biomarkers associated with prognosis. We identified two major subtypes of gastric adenocarcinoma differentially associated with overall survival (P = 0.025). Genes that were differentially expressed were identified using specific criteria (P < 0.001 and >1.5-fold); expression of 294 and 116 genes was enriched in good and poor prognosis subtypes, respectively. Genes related to translational elongation and cell cycle were upregulated in the poor prognosis group. Of these genes, upregulation of proteasome subunit beta type 8 PSMB8 and PDZ binding kinase PBK was confirmed by real-time reverse transcription-PCR analysis. PSMB8 or PBK knockdown had no effect on gastric cancer cell proliferation but suppressed cell migration and invasion, respectively. Furthermore, immunohistochemistry analysis of 385 gastric cancer patients revealed that increased nuclear expression of PSMB8 and PBK was correlated with depth of invasion, lymph node metastasis, and lower survival rates. Taken together, two gastric adenocarcinoma subtypes were predictive of prognosis. PSMB8 and PBK were predictive of gastric cancer prognosis and could be potential gastric cancer subtype-specific biomarkers. PMID- 26894980 TI - A Biomechanical Comparison of Isometric and Anatomic Medial Patellofemoral Ligament Reconstruction. PMID- 26894976 TI - Lipid-sensors, enigmatic-orphan and orphan nuclear receptors as therapeutic targets in breast-cancer. AB - Breast-cancer is heterogeneous and consists of various groups with different biological characteristics. Innovative pharmacological approaches accounting for this heterogeneity are needed. The forty eight human Nuclear-Hormone-Receptors are ligand-dependent transcription-factors and are classified into Endocrine Receptors, Adopted-Orphan-Receptors (Lipid-sensors and Enigmatic-Orphans) and Orphan-receptors. Nuclear-Receptors represent ideal targets for the design/synthesis of pharmacological ligands. We provide an overview of the literature available on the expression and potential role played by Lipid sensors, Enigmatic-Orphans and Orphan-Receptors in breast-cancer. The data are complemented by an analysis of the expression levels of each selected Nuclear Receptor in the PAM50 breast-cancer groups, following re-elaboration of the data publicly available. The major aim is to support the idea that some of the Nuclear Receptors represent largely unexploited therapeutic-targets in breast-cancer treatment/chemo-prevention. On the basis of our analysis, we conclude that the Lipid-Sensors, NR1C3, NR1H2 and NR1H3 are likely to be onco-suppressors in breast cancer. The Enigmatic-Orphans, NR1F1 NR2A1 and NR3B3 as well as the Orphan Receptors, NR0B1, NR0B2, NR1D1, NR2F1, NR2F2 and NR4A3 exert a similar action. These Nuclear-Receptors represent candidates for the development of therapeutic strategies aimed at increasing their expression or activating them in tumor cells. The group of Nuclear-Receptors endowed with potential oncogenic properties consists of the Lipid-Sensors, NR1C2 and NR1I2, the Enigmatic-Orphans, NR1F3, NR3B1 and NR5A2, as well as the Orphan-Receptors, NR2E1, NR2E3 and NR6A1. These oncogenic Nuclear-Receptors should be targeted with selective antagonists, reverse-agonists or agents/strategies capable of reducing their expression in breast-cancer cells. PMID- 26894979 TI - Neurons and guidance cues in retinal vascular diseases. PMID- 26894978 TI - Mitochondrial stress controls the radiosensitivity of the oxygen effect: Implications for radiotherapy. AB - It has been more than 60 years since the discovery of the oxygen effect that empirically demonstrates the direct association between cell radiosensitivity and oxygen tension, important parameters in radiotherapy. Yet the mechanisms underlying this principal tenet of radiobiology are poorly understood. Better understanding of the oxygen effect may explain difficulty in eliminating hypoxic tumor cells, a major cause of regrowth after therapy. Our analysis utilizes the Howard-Flanders and Alper formula, which describes the relationship of radiosensitivity with oxygen tension. Here, we assign and qualitatively assess the relative contributions of two important mechanisms. The first mechanism involves the emission of reactive oxygen species from the mitochondrial electron transport chain, which increases with oxygen tension. The second mechanism is related to an energy and repair deficit, which increases with hypoxia. Following a radiation exposure, the uncoupling of the oxidative phosphorylation system (proton leak) in mitochondria lowers the emission of reactive oxygen species which has implications for fractionated radiotherapy, particularly of hypoxic tumors. Our analysis shows that, in oxygenated tumor and normal cells, mitochondria, rather than the nucleus, are the primary loci of radiotherapy effects, especially for low linear energy transfer radiation. Therefore, the oxygen effect can be explained by radiation-induced effects in mitochondria that generate reactive oxygen species, which in turn indirectly target nuclear DNA. PMID- 26894981 TI - Interaction between deglutition, tongue posture, and malocclusion: A comparison of intraoral compartment formation in subjects with neutral occlusion or different types of malocclusion. AB - OBJECTIVE: To test the null hypothesis of no significant difference in terms of intraoral pressure curve characteristics assessed simultaneously at the subpalatal space (SPS) and the vestibular space (VS), during different oral postures, between four groups with either an Angle Class II/1 (II1), Angle Class II/2 (II2), anterior open bite (O) malocclusion, or a neutral occlusion control group (I). MATERIALS AND METHODS: Intraoral pressure recordings were performed simultaneously in the VS and SPS of 69 consecutive subjects (nII1 = 15; nII2 = 17; nO = 17; nI = 20; mean age/standard deviation 18.43/6.60 years). Assessments included defined sections of open mouth posture (OMP, 30 seconds), anteriorly closed mouth condition (60 seconds), dynamics by a tongue repositioning maneuver (TRM, 60 seconds), swallowing, and positive pressure generation (PP, 10 seconds). Interactions of malocclusion, compartment location, and posture on pressure curve characteristics were analyzed by Kruskal-Wallis and Mann-Whitney U-tests, adopting an alpha level of 5%. RESULTS: Globally significant group differences were detected at the VS (plateau duration and median peak heights during TRM; area under pressure curve [AUC] during PP) and SPS (AUC during TRM and PP). Subjects with anteriorly nonopen dental configurations (groups I and II2) were able to keep negative pressure levels at the VS for longer time periods during TRM, compared to groups O and II1. CONCLUSIONS: The null hypothesis was rejected for mean VS plateau durations and peak heights and for SPS AUC. Negative pressures at the VS may stabilize outer soft tissues passively and may explain the dental arch form shaping effect by mimic muscles. PMID- 26894982 TI - Bis-Tridentate Ir(III) Complexes with Nearly Unitary RGB Phosphorescence and Organic Light-Emitting Diodes with External Quantum Efficiency Exceeding 31%. AB - A new class of neutral bis-tridentate Ir(III) metal complexes that show nearly unitary red, green, and blue emissions in solution is prepared and employed for the fabrication of both monochrome and white-emitting organic light-emitting diodes, among which a green device gives external quantum efficiency exceeding 31%. PMID- 26894983 TI - A novel electrochemical aptasensor based on Y-shape structure of dual-aptamer complementary strand conjugate for ultrasensitive detection of myoglobin. AB - Monitoring of myoglobin (Mb) in human blood serum is highly in demand for early diagnosis of acute myocardial infarction (AMI). Here, a novel electrochemical aptasensor was developed for ultrasensitive and selective detection of Mb, based on Y-shape structure of dual-aptamer (DApt)-complementary strand of aptamer (CS) conjugate, gold electrode and exonuclease I (Exo I). The designed aptasensor obtains features of gold, such as high electrochemical conductivity and large surface area, property of Y-shape structure of DApt-CS conjugate to function as a gate and obstacle for the access of redox probe to the surface of electrode, as well as high specificity and sensitivity of aptamer toward its target and Exo I as an enzyme which specifically degrades the 3'-end of single-stranded DNA (ssDNA). In the absence of Mb, the Y-shape structure remains intact. So, a weak electrochemical signal is observed. Upon addition of target, the DApt leave the CS and bind to Mb, leading to disassembly of Y-shape structure and following the addition of Exo I, a strong electrochemical signal could be recorded. The fabricated aptasensor showed high selectivity toward Mb with a limit of detection (LOD) as low as 27 pM. Besides, the developed aptasensor was effectively applied to detect Mb in human serum. PMID- 26894984 TI - A label-free ultrasensitive fluorescence detection of viable Salmonella enteritidis using enzyme-induced cascade two-stage toehold strand-displacement driven assembly of G-quadruplex DNA. AB - The harm of Salmonella enteritidis (S. enteritidis ) to public health mainly by contaminating fresh food and water emphasizes the urgent need for rapid detection techniques to help control the spread of the pathogen. In this assay, an newly designed capture probe complex that contained specific S. enteritidis-aptamer and hybridized signal target sequence was used for viable S. enteritidis recognition directly. In the presence of the target S. enteritidis, single-stranded target sequences were liberated and initiated the replication-cleavage reaction, producing numerous G-quadruplex structures with a linker on the 3'-end. And then, the sensing system took innovative advantage of quadratic linker-induced strand displacement for the first time to release target sequence in succession, leading to the cyclic reuse of the target sequences and cascade signal amplification, thereby achieving the successive production of G-quadruplex structures. The fluorescent dye, N-Methyl mesoporphyrin IX, binded to these G-quadruplex structures and generated significantly enhanced fluorescent signals to achieve highly sensitive detection of S. enteritidis down to 60 CFU/mL with a linear range from 10(2) to 10(7)CFU/mL. By coupling the cascade two-stage target sequences-recyclable toehold strand-displacement with aptamer-based target recognition successfully, it is the first report on a novel non-label, modification-free and DNA extraction-free ultrasensitive fluorescence biosensor for detecting viable S. enteritidis directly, which can discriminate from dead S. enteritidis. PMID- 26894985 TI - Gold-based hybrid nanomaterials for biosensing and molecular diagnostic applications. AB - The properties of gold nanomaterials are particularly of interest to many researchers, since they show unique physiochemical properties such as optical adsorption of specific wavelength of light, high electrical conductance with rich surface electrons, and facile surface modification with sulfhydryl groups. These properties have facilitated the use of gold nanomaterials in the development of various hybrid systems for biosensors and molecular diagnostics. Combined with various synthetic materials such as fluorescence dyes, polymers, oligonucleotides, graphene oxides (GO), and quantum dots (QDs), the gold-based hybrid nanomaterials offer multi-functionalities in molecular detection with high specificity and sensitivity. These two aspects result in the increase of detection speed as well as the lower detection limits, having shown that this diagnosis method is more effective than other conventional ones. In this review, we have highlighted various examples of nanomaterials for biosensing and molecular diagnostics. The gold-based hybrid systems are categorized by three distinct detection approaches, in which include (1) optical, such as surface plasmon resonance (SPR), RAMAN, and surface-enhanced Raman scattering (SERS), (2) fluorescence, such as forster resonance energy transfer (FRET) and nanomaterial surface energy transfer (NSET), and (3) electrochemical, such as potentiometic, amperometric, and conductometric. Each example provides the detailed mechanism of molecular detection as well as the supporting experimental result with the limit of detection (LOD). Lastly, future perspective on novel development of gold-based hybrid nanomaterials is discussed as well as their challenges. PMID- 26894986 TI - Recognition-induced covalent capturing and labeling as a general strategy for protein detection. AB - In this work we have developed a peptide-based method for protein detection, termed as "Recognition-induced Covalent Capturing and Labeling" (RCCL). In this method, upon binding of the peptide with the target protein, electrochemically controlled and metal catalyzed oxidative cross-linking can be induced between the peptide and the target protein. Specifically, the peptide and the target protein are cross-linked by the formation of dityrosine between tyrosine moieties of the two molecules. Meanwhile, the dityrosine formed in this manner also has fluorescent signal readout. Therefore, the proposed method needs only one probe for the target protein, and the initial non-covalent molecular recognition can be finalized by cross-linking between the peptide and the target, while the dityrosine formed between peptide and protein can also act as a signal reporter, thereby greatly simplifying the design. Moreover, the robust covalent capturing via RCCL also enables detection in complex biological and clinical samples. These results point to the prospect of using RCCL as a promising method in protein detection in the future. PMID- 26894987 TI - Diazonium-based impedimetric aptasensor for the rapid label-free detection of Salmonella typhimurium in food sample. AB - Fast and accurate detection of microorganisms is of key importance in clinical analysis and in food and water quality monitoring. Salmonella typhimurium is responsible for about a third of all cases of foodborne diseases and consequently, its fast detection is of great importance for ensuring the safety of foodstuffs. We report the development of a label-free impedimetric aptamer based biosensor for S. typhimurium detection. The aptamer biosensor was fabricated by grafting a diazonium-supporting layer onto screen-printed carbon electrodes (SPEs), via electrochemical or chemical approaches, followed by chemical immobilisation of aminated-aptamer. FTIR-ATR, contact angle and electrochemical measurements were used to monitor the fabrication process. Results showed that electrochemical immobilisation of the diazonium-grafting layer allowed the formation of a denser aptamer layer, which resulted in higher sensitivity. The developed aptamer-biosensor responded linearly, on a logarithm scale, over the concentration range 1 * 10(1) to 1 * 10(8)CFU mL(-1), with a limit of quantification (LOQ) of 1 * 10(1) CFU mL(-1) and a limit of detection (LOD) of 6 CFU mL(-1). Selectivity studies showed that the aptamer biosensor could discriminate S. typhimurium from 6 other model bacteria strains. Finally, recovery studies demonstrated its suitability for the detection of S. typhimurium in spiked (1 * 10(2), 1 * 10(4) and 1 * 10(6) CFU mL(-1)) apple juice samples. PMID- 26894988 TI - Codelivery of Doxorubicin and shAkt1 by Poly(ethylenimine)-Glycyrrhetinic Acid Nanoparticles To Induce Autophagy-Mediated Liver Cancer Combination Therapy. AB - Combination therapy has been developed as a promising therapeutic approach for hepatocellular carcinoma therapy. Here we report a low toxicity and high performance nanoparticle system that was self-assembled from a poly(ethylenimine) glycyrrhetinic acid (PEI-GA) amphiphilic copolymer as a versatile gene/drug dual delivery nanoplatform. PEI-GA was synthesized by chemical conjugation of hydrophobic GA moieties to the hydrophilic PEI backbone via an acylation reaction. The PEI-GA nanocarrier could encapsulate doxorubicin (DOX) efficiently with loading level about 12% and further condense DNA to form PEI-GA/DOX/DNA complexes to codeliver drug and gene. The diameter of the complexes is 102 +/- 19 nm with zeta potential of 19.6 +/- 0.2 mV. Furthermore, the complexes possess liver cancer targeting ability and could promote liver cancer HepG2 cell internalization. Apoptosis of cells could be induced by chemotherapy of DOX, and PI3K/Akt/mTOR signaling pathway acts a beneficial effect on the modulation of autophagy. Here, it is revealed that utilizing PEI-GA/DOX/shAkt1 complexes results in effective autophagy and apoptosis, which are useful to cause cell death. The induction of superfluous autophagy is reported to induce type-II cell death and also could increase the sensity of chemotherapy to tumor cells. In this case, combining autophagy and apoptosis is meaningful for oncotherapy. In this study, PEI-GA/DOX/shAkt1 has demonstrated favorable tumor target ability, little side effects, and ideal antitumor efficacy. PMID- 26894989 TI - Amphiphilic (Phthalocyaninato) (Porphyrinato) Europium Triple-Decker Nanoribbons with Air-Stable Ambipolar OFET Performance. AB - An amphiphilic mixed (phthalocyaninato) (porphyrinato) europium(III) triple decker complex [Pc(OPh)8]Eu[Pc(OPh)8]Eu[TP(C=CCOOH)PP] (1) with potential ambipolar semiconducting HOMO and LUMO energy levels has been designed, synthesized, and characterized. The OFET devices fabricated by quasi-Langmuir Shafer (QLS) technique at the air/water interface with nanoparticle morphology display hole mobility of 7.0 * 10(-7) cm(2) V(-1) s(-1) and electron mobility of 7.5 * 10(-7) cm(2) V(-1) s(-1), which reflects its ambipolar semiconducting nature. However, the performance of the devices fabricated via a "phase-transfer" method from n-hexane with one-dimensional nanoribbon morphology was significantly improved by 3-6 orders of magnitude in terms of hole and electron mobilities, 0.11 and 4 * 10(-4) cm(2) V(-1) s(-1), due to the enhanced pi-pi interaction in the direction perpendicular to the tetrapyrrole rings associated with the formation of a dimeric supramolecular structure building block depending on the intermolecular hydrogen bonding between the neighboring triple-decker molecules in the one-dimensional nanoribbons. PMID- 26894990 TI - HIV vulnerability and the erasure of sexual and gender diversity in Abidjan, Cote d'Ivoire. AB - In the fight against concentrated HIV epidemics, men who have sex with men (MSM) are often framed as a homogeneous population, with little attention paid to sexual and gender diversity and its impact on HIV vulnerability. This article draws on ethnographic research conducted in Abidjan, Cote d'Ivoire among les branches - a local term encompassing several categories of same-sex desire and practice. In the context of increased HIV prevention programming targeting Ivoirian sexual and gender minorities, such diversity is effectively erased. This obfuscation of difference has particularly negative impacts for travestis, who may be at higher risk for HIV infection, though research and prevention efforts in which they are grouped with 'MSM' render them underrepresented and make their vulnerability difficult to quantify. Branches whose class and/or ethnic backgrounds compound their stigmatised status as sexual and gender minorities also bear the burden of this exclusion. Furthermore, some branches deploy 'MSM' as a form of self-identification, further complicating who such categories represent. By highlighting the ways in which constructions of gender and sexuality within HIV/AIDS programming obscure complex social realities, I aim to reorient thinking around the development of purposeful HIV programming that engages the complexity of sexual and gender minority experience. PMID- 26894991 TI - Orchestration of B lymphoid cells and their inner myeloid by Bach. AB - The transcription repressor Bach2 is required for class switch recombination and somatic hypermutation of antibody genes in B cells, and proper development of effector and regulatory T cells. In addition, Bach2 and its related factor Bach1 promote B cell commitment of progenitor cells by repressing myeloid-related genes. Bach2 and the myeloid regulators C/EBPbeta and C/EBPalpha mutually repress their expression, forming a gene regulatory network (GRN) that dictates the process of lineage commitment. Bach2 forms another GRN with the plasma cell regulator Blimp-1, in which Bach2 and Blimp-1 mutually repress their expression. Since Bach2 expression is reduced in plasma cells, the repression of myeloid related genes in B cells may be dissolved upon terminal differentiation of B cells to plasma cells. The Bach2 GRNs support the myeloid-based model of hematopoiesis. Myeloid-like characteristics suppressed or manifested in B cells by modifying differentiation trajectories of B and myeloid cells may be termed as 'inner myeloid' after the concept of 'inner fish'. PMID- 26894992 TI - Feeling 'too fat' rather than being 'too fat' increases unhealthy eating habits among adolescents - even in boys. AB - BACKGROUND: Adolescence is a period of gender-specific physical changes, during which eating habits develop. To better understand what factors determine unhealthy eating habits such as dieting to lose weight, skipping meals, and consumption of unhealthy foods, we studied how physical measurements and body perception relate to eating habits in boys and girls, before and during adolescence. METHODS: For this cross-sectional study, we obtained data from both written questionnaires and physical measurements of height, weight, and waist circumference (WC). RESULTS: Dieting to lose weight and skipping breakfast were more common among adolescents than among younger boys and girls (p<0.05). The strongest risk factor for dieting in both boys and girls was perception of overweight, which persisted after adjusting for age and for being overweight (p<0.01). Another independent risk factor for dieting behaviour was overweight, as defined by body mass index (BMI) among boys (p<0.01) and WC among girls (p<0.05). In both boys and girls, skipping breakfast was associated with both a more negative body perception and higher BMI (p<0.05). Skipping breakfast was also associated with age- and gender-specific unhealthy eating habits such as skipping other meals, lower consumption of fruits and vegetables, and higher consumption of sweets and sugary drinks (p<0.05). CONCLUSION: Body perception among adolescents is an important factor relating to unhealthy eating habits, not only in girls, but even in boys. Focus on body perception and eating breakfast daily is crucial for the development of healthy food consumption behaviours during adolescence and tracking into adulthood. PMID- 26894993 TI - beta-HCG Elevation in Wilms Tumor: An Uncommon Presentation. AB - Wilms tumor (nephroblastoma) is a readily diagnosed common abdominal tumor in children. Rarely, it may present with factors that may confound the diagnosis. We report a 6-year-old female child who presented with a rapidly growing and invasive abdominal mass with the histopathologic features of Wilms tumor associated with an elevated serum beta human chorionic gonadotropin, which has not been previously reported in this condition. PMID- 26894995 TI - Efficient Z-scheme charge separation in novel vertically aligned ZnO/CdSSe nanotrees. AB - A new tree-like ZnO/CdSSe nanocomposite with CdSSe branches grown on ZnO nanowires prepared via a two-step chemical vapor deposition is presented. The nanotrees (NTs) are vertically aligned on a substrate. The CdSSe branches result in strong visible light absorption and form a type-II heterojunction with the ZnO stem that facilitates efficient electron transfer. A combination of photoluminescence spectroscopy and lifetime measurements indicates that the NTs are promising materials for applications that benefit from a Z-scheme charge transfer mechanism. Vertically aligned branched ZnO nanowires can provide direct electron transport pathways to substrates and allow for efficient charge separation. These advantages of nanoscale hierarchical heterostructures make ZnO/CdSSe NTs a promising semiconductor material for solar cells, and other opto electronic devices. PMID- 26894994 TI - Identification and Validation of Housekeeping Genes for Gene Expression Analysis of Cancer Stem Cells. AB - The characterization of cancer stem cell (CSC) subpopulation, through the comparison of the gene expression signature in respect to the native cancer cells, is particularly important for the identification of novel and more effective anticancer strategies. However, CSC have peculiar characteristics in terms of adhesion, growth, and metabolism that possibly implies a different modulation of the expression of the most commonly used housekeeping genes (HKG), like b-actin (ACTB). Although it is crucial to identify which are the most stable HKG genes to normalize the data derived from quantitative Real-Time PCR analysis to obtain robust and consistent results, an exhaustive validation of reference genes in CSC is still missing. Here, we isolated CSC spheres from different musculoskeletal sarcomas and carcinomas as a model to investigate on the stability of the mRNA expression of 15 commonly used HKG, in respect to the native cells. The selected genes were analysed for the variation coefficient and compared using the popular algorithms NormFinder and geNorm to evaluate stability ranking. As a result, we found that: 1) Tata Binding Protein (TBP), Tyrosine 3 monooxygenase/tryptophan 5-monooxygenase activation protein zeta polypeptide (YWHAZ), Peptidylprolyl isomerase A (PPIA), and Hydroxymethylbilane synthase (HMBS) are the most stable HKG for the comparison between CSC and native cells; 2) at least four reference genes should be considered for robust results; 3) the use of ACTB should not be recommended, 4) specific HKG should be considered for studies that are focused only on a specific tumor type, like sarcoma or carcinoma. Our results should be taken in consideration for all the studies of gene expression analysis of CSC, and will substantially contribute for future investigations aimed to identify novel anticancer therapy based on CSC targeting. PMID- 26894996 TI - Correction: Road Traffic Injury Prevention Initiatives: A Systematic Review and Metasummary of Effectiveness in Low and Middle Income Countries. PMID- 26894998 TI - Red Cell Distribution Width in Patients with Intermediate Coronary Artery Disease. PMID- 26894997 TI - BinPacker: Packing-Based De Novo Transcriptome Assembly from RNA-seq Data. AB - High-throughput RNA-seq technology has provided an unprecedented opportunity to reveal the very complex structures of transcriptomes. However, it is an important and highly challenging task to assemble vast amounts of short RNA-seq reads into transcriptomes with alternative splicing isoforms. In this study, we present a novel de novo assembler, BinPacker, by modeling the transcriptome assembly problem as tracking a set of trajectories of items with their sizes representing coverage of their corresponding isoforms by solving a series of bin-packing problems. This approach, which subtly integrates coverage information into the procedure, has two exclusive features: 1) only splicing junctions are involved in the assembling procedure; 2) massive pell-mell reads are assembled seemingly by moving a comb along junction edges on a splicing graph. Being tested on both real and simulated RNA-seq datasets, it outperforms almost all the existing de novo assemblers on all the tested datasets, and even outperforms those ab initio assemblers on the real dog dataset. In addition, it runs substantially faster and requires less memory space than most of the assemblers. BinPacker is published under GNU GENERAL PUBLIC LICENSE and the source is available from: http://sourceforge.net/projects/transcriptomeassembly/files/BinPacker_1.0.tar.gz/ ownload. Quick installation version is available from: http://sourceforge.net/projects/transcriptomeassembly/files/BinPacker_binary.tar. z/download. PMID- 26894999 TI - Health Related Absenteeism of Family Physicians in the Negev Region of Israel: A Cross-Sectional Study. AB - Physicians tend to treat their own illnesses differently than the general population, sometimes continuing to come to work when ill. To assess whether family physicians continue to work when ill. A cross-sectional study with a convenience sample. A self-administered, anonymous questionnaire, that included socio-demographic data, questions relating to illness, and reasons for work absenteeism, was completed by family physicians in the Negev region of Israel. 107 physicians participated in the study including 46 women (43 %). The mean age was 45.1 +/- 11.4. Forty physicians (37.4 %) said they come to work with an acute illness, 47 (43.9 %) answered that they do so some of the time, and 19 (17.8 %) said that they did not come to work ill. On a scale from 1 to 10 the mean score for the question as to whether physicians are liable to infect their patients was 7.4, with a higher score meaning more likely to infect. Older physicians were more likely to say that the decision to stay away from work was related to the lack of available physicians (P = 0.002), while board certified physicians were more likely than residents to stay away from work due to an acute illness (P = 0.023). Family physicians in the Negev sometimes work when they are ill. This finding has positive sides related to dedication to patients and the work place, but one cannot ignore the fact that patients may be infected by their physicians. Behavioral guidelines, including social, legal, and ethical aspects, should be formulated on this issue. PMID- 26895002 TI - Active Warming Utilizing Combined IV Fluid and Forced-Air Warming Decreases Hypothermia and Improves Maternal Comfort During Cesarean Delivery: A Randomized Control Trial. AB - BACKGROUND: The aim of this study was to apply both IV fluid and forced-air warming to decrease perioperative hypothermia in women undergoing cesarean delivery with spinal anesthesia. The authors hypothesize that combined-modality active warming (AW) would increase maternal temperature on arrival at the postanesthesia care unit (PACU) and decrease the incidence of maternal perioperative hypothermia (<36 degrees C) compared with no AW. METHODS: Forty-six healthy women (n = 23 per group) undergoing scheduled cesarean delivery with spinal anesthesia (10-12 mg bupivacaine + 10 MUg fentanyl) were enrolled in this double-blinded, randomized controlled trial. Women were randomly assigned to receive either AW (warmed IV fluid and lower body forced-air warmer) or no warming (NW; blankets only). SpotOn Monitoring System was used to measure core temperature intraoperatively and for 1 hour postoperatively. The primary outcome measure was maternal temperature on arrival at the PACU. Secondary outcome measures included incidence of maternal perioperative hypothermia (<36 degrees C), incidence of shivering, thermal comfort scores (0-100 scale), Apgar scores, and umbilical cord blood gas analysis. RESULTS: Demographic, obstetric, and surgical data were similar between study groups. The AW group (35.9 degrees C +/- 0.5 degrees C) had a significantly higher temperature on arrival at the PACU compared with the NW group (35.5 degrees C +/- 0.5 degrees C, P = 0.006; 95% confidence interval of mean difference, 0.1 degrees C-0.7 degrees C). Fourteen (64%) women in the AW group and 20 (91%) in the NW group were hypothermic during the study period (P = 0.031). Median (interquartile range) thermal comfort scores were 100 (95-100) in the AW group and 90 (70-100) in the NW group (P = 0.008). There were no significant differences in the incidence of intraoperative shivering (22% in the AW and 45% in the NW groups; P = 0.11), Apgar scores, or umbilical vein blood gas values between the study groups. CONCLUSIONS: Fluid combined with forced-air warming is effective in decreasing the incidence of perioperative hypothermia and improving maternal thermal comfort. However, despite multimodal AW, the majority of women became hypothermic, and shivering was not prevented. The findings suggest that combined AW for cesarean delivery with spinal anesthesia is difficult, and only modest benefit should be expected. PMID- 26895001 TI - Estimated Maximal Safe Dosages of Tumescent Lidocaine. AB - BACKGROUND: Tumescent lidocaine anesthesia consists of subcutaneous injection of relatively large volumes (up to 4 L or more) of dilute lidocaine (<=1 g/L) and epinephrine (<=1 mg/L). Although tumescent lidocaine anesthesia is used for an increasing variety of surgical procedures, the maximum safe dosage is unknown. Our primary aim in this study was to measure serum lidocaine concentrations after subcutaneous administration of tumescent lidocaine with and without liposuction. Our hypotheses were that even with large doses (i.e., >30 mg/kg), serum lidocaine concentrations would be below levels associated with mild toxicity and that the concentration-time profile would be lower after liposuction than without liposuction. METHODS: Volunteers participated in 1 to 2 infiltration studies without liposuction and then one study with tumescent liposuction totally by local anesthesia. Serum lidocaine concentrations were measured at 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, and 24 hours after each tumescent lidocaine infiltration. Area under the curve (AUCinfinity) of the serum lidocaine concentration-time profiles and peak serum lidocaine concentrations (Cmax) were determined with and without liposuction. For any given milligram per kilogram dosage, the probability that Cmax >6 MUg/mL, the threshold for mild lidocaine toxicity was estimated using tolerance interval analysis. RESULTS: In 41 tumescent infiltration procedures among 14 volunteer subjects, tumescent lidocaine dosages ranged from 19.2 to 52 mg/kg. Measured serum lidocaine concentrations were all <6 MUg/mL over the 24-hour study period. AUCinfinitys with liposuction were significantly less than those without liposuction (P = 0.001). The estimated risk of lidocaine toxicity without liposuction at a dose of 28 mg/kg and with liposuction at a dose of 45 mg/kg was <=1 per 2000. CONCLUSIONS: Preliminary estimates for maximum safe dosages of tumescent lidocaine are 28 mg/kg without liposuction and 45 mg/kg with liposuction. As a result of delayed systemic absorption, these dosages yield serum lidocaine concentrations below levels associated with mild toxicity and are a nonsignificant risk of harm to patients. PMID- 26895003 TI - Lack of significant association between type 2 diabetes mellitus with longitudinal change in diurnal salivary cortisol: the multiethnic study of atherosclerosis. AB - Cross-sectional association has been shown between type 2 diabetes and hypothalamic-pituitary-adrenal (HPA) axis dysregulation; however, the temporality of this association is unknown. Our aim was to determine if type 2 diabetes is associated with longitudinal change in daily cortisol curve features. We hypothesized that the presence of type 2 diabetes may lead to a more blunted and abnormal HPA axis profile over time, suggestive of increased HPA axis dysregulation. This was a longitudinal cohort study, including 580 community dwelling individuals (mean age 63.7 +/- 9.1 years; 52.8 % women) with (n = 90) and without (n = 490) type 2 diabetes who attended two MultiEthnic Study of Atherosclerosis Stress ancillary study exams separated by 6 years. Outcome measures that were collected were wake-up and bedtime cortisol, cortisol awakening response (CAR), total area under the curve (AUC), and early, late, and overall decline slopes. In univariate analyses, wake-up and AUC increased over 6 years more in persons with as compared to those without type 2 diabetes (11 vs. 7 % increase for wake-up and 17 vs. 11 % for AUC). The early decline slope became flatter over time with a greater flattening observed in diabetic compared to non diabetic individuals (23 vs. 9 % flatter); however, the change was only statistically significant for wake-up cortisol (p-value: 0.03). Over time, while CAR was reduced more, late decline and overall decline became flatter, and bedtime cortisol increased less in those with as compared to those without type 2 diabetes, none of these changes were statistically significant in adjusted models. We did not identify any statistically significant change in cortisol curve features over 6 years by type 2 diabetes status. PMID- 26895005 TI - Contradicting Data and Comments on Oldmeadow and Dixson's (2015) "The Association Between Men's Sexist Attitudes and Facial Hair". PMID- 26895004 TI - An Adjuvant-Free Mouse Model of Transdermal Sensitization and Oral Elicitation of Anaphylaxis to Shellfish. AB - BACKGROUND: Shellfish (SF) allergy is a leading cause of systemic anaphylaxis in humans. An adjuvant-free mouse model to evaluate allergenicity and oral anaphylaxis to SF is currently unavailable. Here, we tested the hypothesis that transdermal exposure (TDE) to SF protein extract (SFPE) not only elicits a systemic allergic immune response but also will clinically sensitize mice for oral anaphylaxis. METHODS: Adult BALB/c female mice (6-8 weeks of age) were exposed to saline or SFPE once a week for 4 weeks using a transdermal sensitization method. Systemic SF-specific IgE, IgG1 and IgG2a and total (t)IgE responses were measured using ELISA. Systemic anaphylaxis upon oral SFPE administration was assessed according to clinical symptoms and the hypothermia shock response (HSR). Using individual mouse data, the correlation between the readouts of allergenicity was determined using Pearson's analysis. Spleen-cell IL 4 and IFN-x03B3; responses were determined using primary cell culture and ELISA. RESULTS: TDE to SFPE resulted in marked systemic specific (s)IgE, tIgE, IgG1 and IgG2a responses. Oral challenge with SFPE in sensitized mice (but not controls) elicited systemic anaphylactic clinical reactions and HSR. A strong correlation was observed between sIgE, tIgE and HSR. Spleen cells isolated from allergic mice (but not controls) exhibited memory IL-4 and IFN-x03B3; cytokine responses. CONCLUSION: We report a novel adjuvant-free mouse model of SF allergy with robust quantifiable and correlated readouts of allergenicity that may be used in basic biomedical, preclinical and applied food/nutrition research on SF allergy. PMID- 26895006 TI - Media Literacy Is an Essential Component of HIV Prevention for Young Men Who Have Sex With Men. PMID- 26895007 TI - Secreted Frizzled-Related Protein 5 Attenuates High Phosphate-Induced Calcification in Vascular Smooth Muscle Cells by Inhibiting the Wnt/beta-Catenin Pathway. AB - Vascular calcification (VC) is highly prevalent and represents a major cardiovascular risk factor in chronic kidney disease (CKD) patients. High phosphate (HP) levels are strongly associated with VC in this population. Secreted frizzled-related protein 5 (SFRP5), one of the inhibitors of the Wnt pathway, is a known anti-inflammatory adipokine with a positive effect on metabolic and cardiovascular diseases, in addition to its anticancer potency. However, the role of SFRP5 in the pathophysiology of VC is unclear. This work aimed to study the mechanism of action of SFRP5 on the progression of HP-induced VC, which resembles the CKD-related VC, through its direct effect on vascular smooth muscle cells (VSMCs) in vitro. Addition of SFRP5 significantly inhibited HP-induced calcification of VSMCs as determined by Alizarin red staining and calcium content. The inhibitory effect of SFRP5 on calcification of VSMCs was due to the suppression of HP-induced expression of calcification and osteoblastic markers. In addition, SFRP5 abrogated HP-induced activation of the Wnt/beta catenin pathway, which plays a key role in the pathogenesis of VC. The specificity of SFRP5 for the inhibition of calcification of VSMCs was confirmed by using a neutralizing antibody to SFRP5. Our results suggest that SFRP5 inhibits HP-induced calcification of VSMCs by inhibiting the expression of calcification and osteoblastic markers, as well as the Wnt/beta-catenin pathway. Our study may indicate that SFRP5 is a potential therapeutic agent in calcification of VSMCs. PMID- 26895009 TI - Editors' Notes. PMID- 26895008 TI - Factors Associated with the Serum Myostatin Level in Patients Undergoing Peritoneal Dialysis: Potential Effects of Skeletal Muscle Mass and Vitamin D Receptor Activator Use. AB - Myostatin is a member of the transforming growth factor-beta family, which regulates synthesis and degradation of skeletal muscle proteins and is associated with the development of sarcopenia. It is up-regulated in the skeletal muscle of chronic kidney disease patients and is considered to be involved in the development of uremic sarcopenia. However, serum myostatin levels have rarely been determined, and the relationship between serum myostatin levels with clinical and metabolic factors remains unknown. This cross-sectional study investigated the association between serum myostatin level and clinical factors in 69 outpatients undergoing peritoneal dialysis. Serum myostatin level was determined by commercially available enzyme-linked immunosorbent assay (ELISA). Univariable and multivariable analysis were conducted to determine factors associated with serum myostatin levels. The factors included age, sex, diabetes mellitus, dialysis history, body mass index, residual kidney function, peritoneal dialysate volume, serum biochemistries, and the use of vitamin D receptor activators (VDRAs). Mean serum myostatin level was 7.59 +/- 3.37 ng/mL. There was no association between serum myostatin level and residual kidney function. Serum myostatin levels were significantly and positively associated with lean body mass measured by the creatinine kinetic method and negatively associated with the use of VDRAs after adjustment for potential confounding factors. Our study indicated that serum myostatin levels are associated with skeletal muscle mass and are lower in patients treated with VDRAs. Further studies are necessary to determine the significance of measuring serum myostatin level in patients undergoing peritoneal dialysis. PMID- 26895010 TI - Connecting Collegiate Recreation and Athletics to Leadership. AB - Collegiate recreation and intercollegiate athletics have an impact on individual, group, and community development of students who are participants, employees, and athletes and learn leadership within these environments. This chapter explores and applies leadership frameworks in recreation and athletics. PMID- 26895011 TI - Applying the Multi-Institutional Study of Leadership Findings to Collegiate Recreation and Athletics. AB - This chapter describes ways to implement key findings of the Multi-Institutional Study of Leadership in collegiate recreation and athletic programs. Lessons from NCAA and the NIRSA Leadership Commission are also presented. PMID- 26895012 TI - Linking the Leadership Identity Development Model to Collegiate Recreation and Athletics. AB - The Leadership Identity Development (LID) Model (Komives, Owen, Longerbeam, Mainella, & Osteen, 2005) provides a stage leadership development model for college students that can be applied to collegiate recreation student staff, volunteers, participants, and varsity student-athletes. This chapter provides guidance to implement the model in these settings and to create environments that support development. PMID- 26895013 TI - Opportunities and Challenges for First-Year Student-Athletes Transitioning From High School to College. AB - This chapter discusses the transition from high school to college for student athletes. The concepts of athlete identity and leadership development are discussed through the lens of the high school athlete who attends college as a collegiate athlete and those students who are dealing with a loss of their high school athlete identity. PMID- 26895014 TI - Intercollegiate Athlete as Student Leader. AB - The chapter explores student-athlete campus engagement and challenges faced by athletes that may impede leadership development. The roles of athletic academic advisors, team coaches, and teammates in leadership development are outlined. Current campus initiatives directly related to intercollegiate athlete leadership development are also shared. PMID- 26895015 TI - Collegiate Recreation Student Employee as Student Leader. AB - Collegiate recreation student employment opportunities are found in such areas as facilities, intramurals, aquatics, fitness, and outdoor adventure. Recreation is one of the largest providers of student employment opportunities on campuses across the country with an important role in student employee leadership development. PMID- 26895016 TI - Positive Psychology as a Framework for Leadership Development in Recreation and Sport. AB - This chapter connects concepts and research from positive psychology and leadership studies to support using a strengths-based approach to optimize the leadership development of students involved in recreation and athletics. PMID- 26895017 TI - Adventure Leadership and Experiential Education. AB - This chapter provides background in adventure education and its connection to student leadership pedagogy. An adventure program is the ideal experiential learning setting promoting students' leadership development through direct experience, reflection, and application. PMID- 26895018 TI - Leadership Assessment in Collegiate Recreation and Athletics. AB - This chapter provides the reader with literature and resources for conducting leadership assessment in collegiate recreation and athletics. Current practices and strategies are shared. PMID- 26895019 TI - In Vitro and In Vivo Assessment of Docetaxel Formulation Developed for Esophageal Stents. AB - Esophageal cancer (EC) mostly affects the elderly population and is frequently diagnosed at an advanced stage. Self-expanding metal stents (SEMS) are the most popular mode of palliation, but they are associated with reocclusion caused by tumor growth. To overcome this problem, docetaxel (DTX)-loaded polyurethane formulations were prepared for stent application. The films were evaluated against the cancer cell lines, OE-19 and OE-21, and normal esophageal cell line Het-1A. The DTX and the formulations were evaluated in vitro for the cytotoxicity and in vivo in nude mice. It was found that DTX and the formulations have a weak activity against the EC cell lines and an even weaker activity against Het-1A cell line. Preliminary in vivo studies showed skin toxicity in nude mice necessitating modification of the formulation. Reevaluation in a mouse xenograft model resulted in toxicity at high dose formulations while the low dose formulation exhibited modest advantage over commercial IV formulation; however, there was no significant difference between the commercial IV and blank formulation. DTX combination with an anti-cancer agent having complementary mode of action and non-overlapping toxicity could yield better outcome in future. PMID- 26895021 TI - Clinical Micro-Dose Studies to Explore the Human Pharmacokinetics of Four Selective Inhibitors of Human Nav1.7 Voltage-Dependent Sodium Channels. AB - BACKGROUND: The emergence of genetic data linking Nav1.7 sodium channel over- and under- expression to human pain signalling has led to an interest in the treatment of chronic pain through inhibition of Nav1.7 channels. OBJECTIVE: We describe the pharmacokinetic (PK) results of a clinical microdose study performed with four potent and selective Nav1.7 inhibitors and the subsequent modelling resulting in the selection of a single compound to explore Nav1.7 pharmacology at higher doses. METHODS: A clinical microdose study to investigate the intravenous and oral PK of four compounds (PF-05089771, PF-05150122, PF-05186462 and PF 05241328) was performed in healthy volunteers. PK parameters were derived via noncompartmental analysis. A physiologically-based PK (PBPK) model was used to predict exposure and multiples of Nav1.7 50 % inhibitory concentration (IC50) for each compound at higher doses. RESULTS: Plasma clearance, volume of distribution and bioavailability ranged from 45 to 392 mL/min/kg, 13 to 36 L/kg and 38 to 110 %, respectively. The PBPK model for PF-05089771 predicted a 1 g oral dose would be required to achieve exposures of approximately 12* Nav1.7 IC50 at maximum concentration (C max), and approximately 3* IC50 after 12 h (minimum concentration [C min] for a twice-daily regimen). Lower multiples of Nav1.7 IC50 were predicted with the same oral doses of PF-05150122, PF-05186462, and PF 05241328. In a subsequent single ascending oral dose clinical study, the predictions for PF-05089771 compared well with observed data. CONCLUSION: Based on the human PK data obtained from the microdose study and subsequent modelling, PF-05089771 provided the best opportunity to explore Nav1.7 blockade for the treatment of acute or chronic pain conditions. PMID- 26895022 TI - Drug-Drug Interactions Between the Anti-Hepatitis C Virus 3D Regimen of Ombitasvir, Paritaprevir/Ritonavir, and Dasabuvir and Eight Commonly Used Medications in Healthy Volunteers. AB - BACKGROUND AND AIMS: The three direct-acting antiviral regimen of ombitasvir/paritaprevir/ritonavir and dasabuvir (3D regimen) is approved for treatment of hepatitis C virus (HCV) genotype 1 infection. Drug-drug interaction (DDI) studies of the 3D regimen and commonly used medications were conducted in healthy volunteers to provide information on coadministering these medications with or without dose adjustments. METHODS: Three phase I studies evaluated DDIs between the 3D regimen (ombitasvir/paritaprevir/ritonavir 25/150/100 mg once daily + dasabuvir 250 mg twice daily) and hydrocodone bitartrate/acetaminophen (5/300 mg), metformin hydrochloride (500 mg), diazepam (2 mg), cyclobenzaprine hydrochloride (5 mg), carisoprodol (250 mg), or sulfamethoxazole/trimethoprim (SMZ/TMP) (800/160 mg twice daily), all administered orally. DDI magnitude was determined using geometric mean ratios and 90 % confidence intervals for the maximum plasma concentration (C max) and area under the plasma concentration-time curve (AUC). RESULTS: Changes in exposures (C max and AUC geometric mean ratios) of acetaminophen, metformin, sulfamethoxazole, trimethoprim, and diazepam were <=25 % upon coadministration with the 3D regimen. The C max and AUC of nordiazepam, an active metabolite of diazepam, increased by 10 % and decreased by 44 %, respectively. Exposures of cyclobenzaprine and carisoprodol decreased by <=40 and <=46 %, respectively, whereas exposures of hydrocodone increased up to 90 %. Ombitasvir, paritaprevir, ritonavir, and dasabuvir exposures changed by <=25 %, except for a 37 % decrease in paritaprevir C max with metformin and a 33 % increase in dasabuvir AUC with SMZ/TMP. CONCLUSIONS: Acetaminophen, metformin, sulfamethoxazole, and trimethoprim can be coadministered with the 3D regimen without dose adjustment. Higher doses may be needed for diazepam, cyclobenzaprine, and carisoprodol based on clinical monitoring. A 50 % lower dose and/or clinical monitoring should be considered for hydrocodone. No dose adjustment is necessary for the 3D regimen. PMID- 26895023 TI - Natural head position and lower incisor irregularity: Is there a relationship? AB - OBJECTIVE: The aim of this study was to assess the relationship between dynamic measurements of natural head position (NHP) and lower incisor irregularity to identify potential gender differences. MATERIALS AND METHODS: A total of 103 plaster models and dynamic NHP measurements were taken from 51 male (mean age: 14.20 +/- 2.51 years) and 52 female (mean age: 15.02 +/- 2.67 years) subjects. The dynamic NHP data were gathered by using an inclinometer device and a portable data logger. Lower incisor irregularity was measured with Little's irregularity index. The Mann-Whitney U and Kruskal-Wallis rank tests were used at a significance level of p < 0.05. To evaluate the correlation between NHP and lower incisor irregularity, Spearman correlation coefficients (r) were calculated. RESULTS: There were significant gender differences in the sagittal measurements of NHP (p = 0.031) and incisor irregularity (p = 0.023). A Kruskal-Wallis test revealed no significant difference in NHP measurements between subjects presenting different levels of irregularity. Females displayed no significant correlation between incisor irregularity and any NHP measurement. However, in the males high correlation coefficients between incisor irregularity and sagittal NHP measurements (r = 0.369; p = 0.008) were noted. CONCLUSION: Significant correlations between lower incisor irregularity and sagittal NHP measurements in males were observed. Females had a more forwardly inclined NHP than males. Moreover, male subjects displayed greater incisor irregularity than female subjects. PMID- 26895024 TI - Shear bond strength of brackets on restorative materials: Comparison on various dental restorative materials using the universal primer Monobond(r) Plus. AB - OBJECTIVE: The purpose of this work was to analyze surfaces consisting of different restorative materials for shear bond strength (SBS) and failure patterns of metal and ceramic brackets. Bonding involved the use of a universal primer (Monobond(r) Plus, Ivoclar Vivadent). MATERIALS AND METHODS: Six restorative materials were tested, including one composite resin (Clearfil MajestyTM Posterior, Kuraray Noritake Dental), one glass-ceramic material (IPS Empress(r) Esthetic, Ivoclar Vivadent), one oxide-ceramic material (CORiTEC Zr transpa Disc, imes-icore), two base-metal alloys (remanium(r) star, Dentaurum; Colado(r) CC, Ivoclar Vivadent), and one palladium-based alloy (Callisto(r) 75 Pd, Ivoclar Vivadent). Bovine incisors served as controls. Both metal and ceramic brackets (discovery(r)/discovery(r) pearl; Dentaurum) were bonded to the restorative surfaces after sandblasting and pretreatment with Monobond(r) Plus. A setup modified from DIN 13990-2 was used for SBS testing and adhesive remnant index (ARI)-based analysis of failure patterns. RESULTS: The metal brackets showed the highest mean SBS values on the glass-ceramic material (68.61 N/mm(2)) and the composite resin (67.58 N/mm(2)) and the lowest mean SBS on one of the base-metal alloys (Colado(r) CC; 14.01 N/mm(2)). The ceramic brackets showed the highest mean SBS on the glass-ceramic material (63.36 N/mm(2)) and the lowest mean SBS on the palladium-based alloy (38.48 N/mm(2)). Significant differences between the metal and ceramic brackets were observed in terms of both SBS values and ARI scores (p < 0.05). Under both bracket types, fractures of the composite resin and the glass-ceramic samples were observed upon debonding. Opaque restorative materials under metal brackets were found to involve undercuring of the adhesive. CONCLUSIONS: Monobond(r) Plus succeeded in generating high bond strengths of both bracket types on all restorative surfaces. Given our observations of cohesive fracture (including cases of surface avulsion) of the composite-resin and the glass-ceramic samples, we recommend against using these material combinations in clinical practice. PMID- 26895025 TI - Chemical Tools of Octopus maya during Crab Predation Are Also Active on Conspecifics. AB - Octopus maya is a major socio-economic resource from the Yucatan Peninsula in Mexico. In this study we report for the first time the chemical composition of the saliva of O. maya and its effect on natural prey, i.e. the blue crab (Callinectes sapidus), the crown conch snail (Melongena corona bispinosa), as well as conspecifics. Salivary posterior glands were collected from octopus caught by local fishers and extracted with water; this extract paralyzed and predigested crabs when it was injected into the third pereiopod. The water extract was fractionated by membrane ultrafiltration with a molecular weight cut off of 3 kDa leading to a metabolic phase (>3 kDa) and a neurotoxic fraction (<3 kDa). The neurotoxic fraction injected in the crabs caused paralysis and postural changes. Crabs recovered to their initial condition within two hours, which suggests that the effects of the neurotoxic fraction were reversible. The neurotoxic fraction was also active on O. maya conspecifics, partly paralyzing and sedating them; this suggests that octopus saliva might be used among conspecifics for defense and for reduction of competition. Bioguided separation of the neurotoxic fraction by chromatography led to a paralysis fraction and a relaxing fraction. The paralyzing activity of the saliva was exerted by amino acids, while the relaxing activity was due to the presence of serotonin. Prey handling studies revealed that O. maya punctures the eye or arthrodial membrane when predating blue crabs and uses the radula to bore through crown conch shells; these differing strategies may help O. maya to reduce the time needed to handle its prey. PMID- 26895026 TI - Substrate and Enzyme Specificity of the Kinetic Isotope Effects Associated with the Dioxygenation of Nitroaromatic Contaminants. AB - Compound-specific isotope analysis (CSIA) is a promising approach for tracking biotransformation of organic pollutants, but isotope fractionation associated with aromatic oxygenations is only poorly understood. We investigated the dioxygenation of a series of nitroaromatic compounds to the corresponding catechols by two enzymes, namely, nitrobenzene and 2-nitrotoluene dioxygenase (NBDO and 2NTDO) to elucidate the enzyme- and substrate-specificity of C and H isotope fractionation. While the apparent (13)C- and (2)H-kinetic isotope effects of nitrobenzene, nitrotoluene isomers, 2,6-dinitrotoluene, and naphthalene dioxygenation by NBDO varied considerably, the correlation of C and H isotope fractionation revealed a common mechanism for nitrobenzene and nitrotoluenes. Similar observations were made for the dioxygenation of these substrates by 2NTDO. Evaluation of reaction kinetics, isotope effects, and commitment-to catalysis based on experiment and theory showed that rates of dioxygenation are determined by the enzymatic O2 activation and aromatic C oxygenation. The contribution of enzymatic O2 activation to the reaction rate varies for different nitroaromatic substrates of NBDO and 2NTDO. Because aromatic dioxygenation by nonheme iron dioxygenases is frequently the initial step of biodegradation, O2 activation kinetics may also have been responsible for the minor isotope fractionation reported for the oxygenation of other aromatic contaminants. PMID- 26895020 TI - Predicting Drug Extraction in the Human Gut Wall: Assessing Contributions from Drug Metabolizing Enzymes and Transporter Proteins using Preclinical Models. AB - Intestinal metabolism can limit oral bioavailability of drugs and increase the risk of drug interactions. It is therefore important to be able to predict and quantify it in drug discovery and early development. In recent years, a plethora of models-in vivo, in situ and in vitro-have been discussed in the literature. The primary objective of this review is to summarize the current knowledge in the quantitative prediction of gut-wall metabolism. As well as discussing the successes of current models for intestinal metabolism, the challenges in the establishment of good preclinical models are highlighted, including species differences in the isoforms; regional abundances and activities of drug metabolizing enzymes; the interplay of enzyme-transporter proteins; and lack of knowledge on enzyme abundances and availability of empirical scaling factors. Due to its broad specificity and high abundance in the intestine, CYP3A is the enzyme that is frequently implicated in human gut metabolism and is therefore the major focus of this review. A strategy to assess the impact of gut wall metabolism on oral bioavailability during drug discovery and early development phases is presented. Current gaps in the mechanistic understanding and the prediction of gut metabolism are highlighted, with suggestions on how they can be overcome in the future. PMID- 26895027 TI - Endemic insular and coastal Tunisian date palm genetic diversity. AB - The breeding of crop species relies on the valorisation of ancestral or wild varieties to enrich the cultivated germplasm. The Tunisian date palm genetic patrimony is being threatened by diversity loss and global climate change. We have conducted a genetic study to evaluate the potential of spontaneous coastal resources to improve the currently exploited Tunisian date palm genetic pool. Eighteen microsatellite loci of Phoenix dactylifera L. were used to compare the genetic diversity of coastal accessions from Kerkennah, Djerba, Gabes and continental date palm accessions from Tozeur. A collection of 105 date palms from the four regions was analysed. This study has provided us with an extensive understanding of the local genetic diversity and its distribution. The coastal date palm genotypes exhibit a high and specific genetic diversity. These genotypes are certainly an untapped reservoir of agronomically important genes to improve cultivated germplasm in continental date palm. PMID- 26895028 TI - Medication Administration Errors in a University Hospital. AB - OBJECTIVE: To measure the rates of medication administration errors in medical wards at Ain Shams University Hospital and to identify significant determinants of medication administration errors. METHODS: A descriptive direct-observational study of drug administration errors was carried out at medical wards of Ain Shams University hospital for a period of 3 months. A standardized observational checklist was used to observe the nurse during giving medications, and a medical record audit form was used to assess documentation. The error rates per observation, nurse, and patient were calculated, and the association between error rates and characteristics of each category was tested using linear regression to identify potential risk factors. RESULTS: The study included 237 patients and 28 nurses. The final number of drug administration observations was 2090 after excluding 310 omissions. A total of 5531 errors were observed with an average number of 2.67 errors per observation. More than 85% of the observations had at least one error, and the overall error rate was 37.68% (per hundred error opportunities). The highest error rate was detected in injections especially the intravenous route (39.58%). The most frequent errors were wrong documentation (90.96%) and wrong technique (78.90%), and the least was wrong patient (0.05%). The significant independent determinants of medication administration errors were high number of shifts taken by nurse per month, night shifts, weekends, elderly patient, and illiteracy. CONCLUSION: Medication administration errors represent a major problem in the hospital that needs urgent intervention to optimize medication administration process. The intervention should consider the identified significant determinants of medication administration errors. PMID- 26895029 TI - Aluminum-induced pneumoconiosis confirmed by analytical scanning electron microscopy: A case report and review of the literature. AB - Aluminum-induced lung injury is an uncommon, yet recognized pneumoconiosis capable of causing severe interstitial fibrosis. Important attention to the clinical history including occupational exposure is an essential component to making the correct diagnosis, despite which careful examination of the lung specimen is necessary to exclude other more common disease entities. We present a case of aluminum-induced pneumoconiosis in the setting of a bilateral lung transplant patient. Additionally, we review the literature on aluminum-induced pneumoconiosis and demonstrate the use of ancillary techniques including backscattered electron imaging and energy-dispersive spectrometry to aid in diagnosis. PMID- 26895030 TI - A method for converting dose-to-medium to dose-to-tissue in Monte Carlo studies of gold nanoparticle-enhanced radiotherapy. AB - Gold nanoparticles (GNPs) have shown potential in recent years as a means of therapeutic dose enhancement in radiation therapy. However, a major challenge in moving towards clinical implementation is the exact characterisation of the dose enhancement they provide. Monte Carlo studies attempt to explore this property, but they often face computational limitations when examining macroscopic scenarios. In this study, a method of converting dose from macroscopic simulations, where the medium is defined as a mixture containing both gold and tissue components, to a mean dose-to-tissue on a microscopic scale was established. Monte Carlo simulations were run for both explicitly-modeled GNPs in tissue and a homogeneous mixture of tissue and gold. A dose ratio was obtained for the conversion of dose scored in a mixture medium to dose-to-tissue in each case. Dose ratios varied from 0.69 to 1.04 for photon sources and 0.97 to 1.03 for electron sources. The dose ratio is highly dependent on the source energy as well as GNP diameter and concentration, though this effect is less pronounced for electron sources. By appropriately weighting the monoenergetic dose ratios obtained, the dose ratio for any arbitrary spectrum can be determined. This allows complex scenarios to be modeled accurately without explicitly simulating each individual GNP. PMID- 26895031 TI - The burden of excluding malrotation in term neonates with bile stained vomiting. AB - PURPOSE: To determine the number of term infants with bilious vomiting (BV) referred to a neonatal surgical centre for exclusion of malrotation by upper gastrointestinal contrast (UGI) examination. METHODS: Retrospective review of term (>37/40) neonates <28 days of age undergoing UGI for exclusion of malrotation between Jan 2010 and Dec 2014 in a neonatal network with 30,000 term deliveries annually. Only infants with BV in the absence of alternative clinical/radiological diagnosis were included. RESULTS: One hundred and sixty-six infants met the inclusion criteria. Fourteen (9 %) infants had malrotation diagnosed by UGI and confirmed at laparotomy. Only 1 of 110 infants referred at 0 2 days of age had positive UGI compared to 13 of 56 infants referred after this age (p < 0.01). An increase in referrals followed the death of an infant from midgut volvulus and as a result one in 500 term infants are currently being referred. CONCLUSION: Increasing awareness of the potential consequences of bilious vomiting appears to have resulted in increased referrals with no increase in detection of malrotation. Prospective studies are required to determine whether investigation of all infants with unexplained bilious vomiting is required and if it is possible to select cases for surgical referral. PMID- 26895032 TI - Pocket ultrasound device as a complement to physical examination for ascites evaluation and guided paracentesis. AB - The pocket ultrasound device (PUD) is a new tool that may be of use in the early detection of ascites. Abdominal ultrasound-guided paracentesis has been reported to decrease the rate of complications due to the procedure, but must be performed in a healthcare setting; this new tool may be a useful on an ambulatory basis. The aim of this study was to determine the diagnostic usefulness of the PUD in the diagnosis of ascites and the safety of guided paracentesis. We conducted a retrospective study that included adult patients suspected of having ascites and in whom an evaluation was performed with the PUD to identify it. Concordance with abdominal ultrasound (AUS) was determined with the Kappa coefficient. Sensitivity (Se), specificity (Sp) and likelihood ratios (LR) were determined and compared with physical examination, AUS, computed tomography and procurement of fluid by paracentesis. Complications resulting from the guided paracentesis were analyzed. 89 participants were included and 40 underwent a paracentesis. The PUD for ascites detection had 95.8 % Se, 81.8 % Sp, 5.27 +LR and 0.05 -LR. It had a concordance with AUS of 0.781 (p < 0.001). Technical problems during the guided paracentesis were present in only two participants (5 %) and three patients (7.5 %) developed minor complications that required no further intervention. There were no severe complications or deaths. This study suggests that the PUD is a reliable tool for ascites detection as a complement to physical examination and appears to be a safe method to perform guided paracentesis. PMID- 26895033 TI - The characteristics of advanced cancer patients followed at home, but admitted to the hospital for the last days of life. AB - Information regarding advanced cancer patients followed at home who are admitted to the hospital in the last days of life are lacking. The aim of this study was to assess the characteristics of patients who were hospitalized in the last days of life after being assisted by a home palliative care team. The secondary outcome was to identify possible risk factors for hospitalization. The charts were analyzed of a consecutive sample of advanced cancer patients admitted to hospital wards in the last days of life after being followed at home by a palliative care team. Of 550 consecutive patients followed at home, 138 (25.1 %) were admitted to the hospital. Younger patients were more likely to die in the hospital. In a logistic risk analysis adjusted for age, patients with lung and head-neck cancer were more likely to die in the hospital. Patients having a female relative or a female consort as a caregiver were more likely to die at home. CAGE-positive patients (7.25 %), and patients with a shorter period of home assistance were more likely transported to hospital before dying (p = 0.00 and p < 0.024, respectively). The most frequent reason for hospital admission was dyspnea. Admission was more frequent to the oncology ward. Patients who were admitted to the hospital died after a mean of 10.2 days (SD 8.2, range 0-40). This study provides preliminary data on the risk factors of hospitalization at the end of life for advanced cancer patients followed at home. PMID- 26895035 TI - Single Electron Transfer-Promoted Photochemical Reactions of Secondary N Trimethylsilylmethyl-N-benzylamines Leading to Aminomethylation of Fullerene C60. AB - Photoreactions between C60 and secondary N-trimethylsilylmethyl-N-benzylamines were explored to evaluate the feasibility of a new method for secondary aminomethylation of electron acceptors. The results show that photoreactions of C60 with these secondary amines in 10% EtOH-toluene occur to form aminomethyl-1,2 dihydrofullerenes predominantly through a pathway involving single electron transfer (SET)-promoted formation of secondary aminium radicals followed by preferential loss of the alpha-trimethylsilyl group. The aminomethyl radicals formed in this manner then couple with C60 or C60(*-) to form radical or anion precursors of the aminomethyl-1,2-dihydrofullerenes. In contrast to thermal and photochemical strategies developed previously, the new SET photochemical approach using alpha-trimethylsilyl-substituted secondary amines is both mild and efficient, and as a result, it should be useful in broadening the library of substituted fullerenes. Moreover, the results should have an impact on the design of SET-promoted C-C bond forming reactions. Specifically, introduction of an alpha-trimethylsilyl group leads to a change in the chemoselectivity of SET promoted reactions of secondary amines with acceptors that typically favor aminium radical N-H deprotonation, leading to N-C bond formation. Finally, symmetric and unsymmetric fulleropyrrolidines are also generated in yields that are highly dependent on the electronic properties of arene ring substituents in amines, irradiation time, and solvent. PMID- 26895034 TI - Regulation of Inflammation by IL-17A and IL-17F Modulates Non-Alcoholic Fatty Liver Disease Pathogenesis. AB - Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide. While it is well-accepted that inflammation is central to NAFLD pathogenesis, the immune pathway(s) orchestrating disease progression are poorly defined. Notably, IL-17RA signaling, via IL-17A, plays an important role in obesity-driven NAFLD pathogenesis. However, the role of the IL-17F, another IL-17RA ligand, in NAFLD pathogenesis has not been examined. Further, the cell types expressing IL-17RA and producing IL-17RA ligands in the pathogenesis of NAFLD have not been defined. Here, IL-17RA-/-, IL-17A-/-, IL-17F-/- and wild type (WT) mice were fed either standard chow diet or methionine and choline deficient diet (MCDD)--a diet known to induce steatosis and hepatic inflammation through beta-oxidation dysfunction--and hepatic inflammation and NAFLD progression were subsequently quantified. MCDD feeding augmented hepatic IL-17RA expression and significantly increased hepatic infiltration of macrophages and IL 17A and IL-17F producing CD4+ and CD8+ T cells in WT mice. In contrast, IL-17RA-/ , IL-17A-/-, and IL-17F-/- mice, despite increased steatosis, exhibited significant protection from hepatocellular damage compared to WT controls. Protection from hepatocellular damage correlated with decreased levels of hepatic T-cell and macrophage infiltration and decreased expression of inflammatory mediators associated with NAFLD. In sum, our results indicate that the IL-17 axis also plays a role in a MCDD-induced model of NAFLD pathogenesis. Further, we show for the first time that IL-17F, and not only IL-17A, plays an important role in NAFLD driven inflammation. PMID- 26895036 TI - Differential proteomic expression of human placenta and fetal development following e-waste lead and cadmium exposure in utero. AB - Prenatal exposure to lead (Pb) and cadmium (Cd) has been associated with a series of physiological problems resulting in fetal growth restriction. We aimed to investigate the effects of Pb and Cd exposure on placental function and the potential mechanisms involved in fetal development. Placental specimens and questionnaires were collected from an e-waste area and a reference area in China. Two-dimensional electrophoresis combined with MALDI-TOF-MS/MS and molecular network relationship were performed to analyze differentially expressed proteins using a compositing sample pool. Compared with the reference group, the exposed group exhibited significantly higher levels of placental Pb and Cd (p<0.01), shorter body length and higher gestational age (p<0.01). After bivariate adjustment in a linear regression model, decreases of 205.05g in weight and 0.44cm in body length were associated with a 10ng/g wt increase in placental Cd. Pb showed a negative trend but lacked statistical significance. Proteomic analysis showed 32 differentially-expressed proteins and were predominantly involved in protein translocation, cytoskeletal structure, and energy metabolism. Fumarate hydratase was down-regulated in the exposed placenta tissues and validated by ELISA. Alterations in placental proteome suggest that imbalances in placental mitochondria respiration might be a vital pathway targeting fetal growth restriction induced by exposure to Cd. PMID- 26895037 TI - Monitoring and predicting the fecal indicator bacteria concentrations from agricultural, mixed land use and urban stormwater runoff. AB - While the urban runoff are increasingly being studied as a source of fecal indicator bacteria (FIB), less is known about the occurrence of FIB in watershed with mixed land use and ongoing land use and land cover (LULC) change. In this study, Escherichia coli (EC) and fecal streptococcus (FS) were monitored from 2012 to 2013 in agricultural, mixed and urban LULC and analyzed according to the most probable number (MPN). Pearson correlation was used to determine the relationship between FIB and environmental parameters (physicochemical and hydrometeorological). Multiple linear regressions (MLR) were used to identify the significant parameters that affect the FIB concentrations and to predict the response of FIB in LULC change. Overall, the FIB concentrations were higher in urban LULC (EC=3.33-7.39; FS=3.30-7.36log10MPN/100mL) possibly because of runoff from commercial market and 100% impervious cover (IC). Also, during early-summer season; this reflects a greater persistence and growth rate of FIB in a warmer environment. During intra-event, however, the FIB concentrations varied according to site condition. Anthropogenic activities and IC influenced the correlation between the FIB concentrations and environmental parameters. Stormwater temperature (TEMP), turbidity, and TSS positively correlated with the FIB concentrations (p>0.01), since IC increased, implying an accumulation of bacterial sources in urban activities. TEMP, BOD5, turbidity, TSS, and antecedent dry days (ADD) were the most significant explanatory variables for FIB as determined in MLR, possibly because they promoted the FIB growth and survival. The model confirmed the FIB concentrations: EC (R(2)=0.71-0.85; NSE=0.72-0.86) and FS (R(2)=0.65-0.83; NSE=0.66-0.84) are predicted to increase due to urbanization. Therefore, these findings will help in stormwater monitoring strategies, designing the best management practice for FIB removal and as input data for stormwater models. PMID- 26895038 TI - Brain Imaging and Cognition after Kidney Transplantation. PMID- 26895039 TI - Erratum to: A prospective study of the cumulative incidence and course of restless legs syndrome in de novo patients with Parkinson's disease during chronic dopaminergic therapy. PMID- 26895041 TI - Enhancement of solubility and antidiabetic effects of Repaglinide using spray drying technique in STZ-induced diabetic rats. AB - The purpose of the study was to enhance the solubility of the poorly water soluble drug, Repaglinide using spray drying based solid dispersion technique by different carriers including Eudragit E100, hydroxyl propyl cellulose Mw 80 000 and poly vinyl pyrollidone K30. Optimization of the best formulation was carried out according to drug solubility, release profile, particle size and angle of repose of the solid dispersions. The optimized sample was characterized using X ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR). The morphology of the dispersions was studied by SEM. The blood glucose lowering effect of spray dried solid dispersions was studied in normal and streptozocin-induced diabetic rats. The results showed that Eudragit E100 in 1:3 ratio could enhance drug solubility by 100-fold. DSC studies indicated a marked change in melting point of the drug possibly due to strong hydrogen bonds between the drug and Eudragit, while FT-IR study did not show obvious interactions between them. According to XRPD results Repaglinide converted to an amorphous state in the spray dried dispersions. Spray dried Repaglinide reduced the blood glucose level significantly during the 8 h of obtaining blood samples in comparison with untreated drug (p < 0.05). PMID- 26895040 TI - Reduced Pancreatic Exocrine Function and Organellar Disarray in a Canine Model of Acute Pancreatitis. AB - The aim of the present study was to investigate the pancreatic exocrine function in a canine model and to analyze the changes in organelles of pancreatic acinar cells during the early stage of acute pancreatitis (AP). AP was induced by retrograde injection of 5% sodium taurocholate (0.5 ml/kg) into the main pancreatic duct of dogs. The induction of AP resulted in serum hyperamylasemia and a marked reduction of amylase activity in the pancreatic fluid (PF). The pancreatic exocrine function was markedly decreased in subjects with AP compared with the control group. After the induction of AP, histological examination showed acinar cell edema, cytoplasmic vacuolization, fibroblasts infiltration, and inflammatory cell infiltration in the interstitium. Electron micrographs after the induction of AP revealed that most of the rough endoplasmic reticulum (RER) were dilated and that some of the ribosomes were no longer located on the RER. The mitochondria were swollen, with shortened and broken cristae. The present study demonstrated, in a canine model, a reduced volume of PF secretion with decreased enzyme secretion during the early stage of AP. Injury of mitochondria and dilatation and degranulation of RER may be responsible for the reduced exocrine function in AP. Furthermore, the present model and results may be useful for researching novel therapeutic measures in AP. PMID- 26895042 TI - Stabilization of DNA liquid crystals on doping with gold nanorods. AB - We report on the impact of doping with gold nanorods (NRs) on the formation and stability of DNA liquid crystals (LCs). Cetyl trimethylammonium (CTAB)-stabilized gold NRs were synthesized using the wet chemistry method. Different textures of cholesteric and columnar mesophases, as well as phase transitions, were observed using a polarized light microscope. It was found that liquid crystalline phases formed in the samples were qualitatively the same and the phase appearance sequence was preserved in the samples regardless of the doping. We show that depending on the concentration of gold NRs present in the phase, nanoparticle doped cholesteric and columnar hexagonal phases existed in wider temperature ranges compared to pure DNA LCs. The potential applications of these liquid crystal-nanoparticle hybrid systems may include the fabrication of new optoelectronic devices and sensors. PMID- 26895043 TI - Study of Transposable Elements and Their Genomic Impact. AB - Transposable elements (TEs) have been considered traditionally as junk DNA, i.e., DNA sequences that despite representing a high proportion of genomes had no evident cellular functions. However, over the last decades, it has become undeniable that not only TE-derived DNA sequences have (and had) a fundamental role during genome evolution, but also TEs have important implications in the origin and evolution of many genomic disorders. This concise review provides a brief overview of the different types of TEs that can be found in genomes, as well as a list of techniques and methods used to study their impact and mobilization. Some of these techniques will be covered in detail in this Method Book. PMID- 26895044 TI - Bacterial Group II Introns: Identification and Mobility Assay. AB - Group II introns are large catalytic RNAs and mobile retroelements that encode a reverse transcriptase. Here, we provide methods for their identification in bacterial genomes and further analysis of their splicing and mobility capacities. PMID- 26895045 TI - In Silico Methods to Identify Exapted Transposable Element Families. AB - Transposable elements (TEs) have recently been shown to have many regulatory roles within the genome. In this chapter, we will examine two in silico methods for analyzing TEs and identifying families that may have acquired such functions. The first method will look at how the overrepresentation of a repeat family in a set of genomic features can be discovered. The example situation of OCT4 binding sites originating from LTR7 TE sequences will be used to show how this method could be applied. The second method will describe how to determine if a TE family exhibits a cell type-specific expression pattern. As an example, we will look at the expression of HERV-H, an endogenous retrovirus known to act as an lncRNA in embryonic stem cells. We will use this example to demonstrate how RNA-seq data can be used to compare cell type expression of repeats. PMID- 26895046 TI - Retrotransposon Capture Sequencing (RC-Seq): A Targeted, High-Throughput Approach to Resolve Somatic L1 Retrotransposition in Humans. AB - Mobile genetic elements (MGEs) are of critical importance in genomics and developmental biology. Polymorphic and somatic MGE insertions have the potential to impact the phenotype of an individual, depending on their genomic locations and functional consequences. However, the identification of polymorphic and somatic insertions among the plethora of copies residing in the genome presents a formidable technical challenge. Whole genome sequencing has the potential to address this problem; however, its efficacy depends on the abundance of cells carrying the new insertion. Robust detection of somatic insertions present in only a subset of cells within a given sample can also be prohibitively expensive due to a requirement for high sequencing depth. Here, we describe retrotransposon capture sequencing (RC-seq), a sequence capture approach in which Illumina libraries are enriched for fragments containing the 5' and 3' termini of specific MGEs. RC-seq allows the detection of known polymorphic insertions present in an individual, as well as the identification of rare or private germline insertions not previously described. Furthermore, RC-seq can be used to detect and characterize somatic insertions, providing a valuable tool to elucidate the extent and characteristics of MGE activity in healthy tissues and in various disease states. PMID- 26895047 TI - Long Interspersed Element Sequencing (L1-Seq): A Method to Identify Somatic LINE 1 Insertions in the Human Genome. AB - L1-seq is a high-throughput sequencing technique which is utilized to identify novel L1 insertions in genomic DNA samples of interest. Using special diagnostic nucleotides unique to the youngest and most active L1 sequence, we can amplify new somatic insertions. This technique has helped to establish the number of L1 insertions present in the general population as well as the variation among individuals with regard to their complement of active L1 elements. More recently, this technique has been employed to assess the level of retrotransposition occurring in various diseases such as cancer. These efforts try to establish a connection between the process of retrotransposition and disease development and/or progression. PMID- 26895048 TI - Combining Amplification Typing of L1 Active Subfamilies (ATLAS) with High Throughput Sequencing. AB - With the advent of new generations of high-throughput sequencing technologies, the catalog of human genome variants created by retrotransposon activity is expanding rapidly. However, despite these advances in describing L1 diversity and the fact that L1 must retrotranspose in the germline or prior to germline partitioning to be evolutionarily successful, direct assessment of de novo L1 retrotransposition in the germline or early embryogenesis has not been achieved for endogenous L1 elements. A direct study of de novo L1 retrotransposition into susceptible loci within sperm DNA (Freeman et al., Hum Mutat 32(8):978-988, 2011) suggested that the rate of L1 retrotransposition in the germline is much lower than previously estimated (<1 in 400 individuals versus 1 in 9 individuals (Kazazian, Nat Genet 22(2):130, 1999). Based on these revised estimates of the L1 retrotransposition rate, we modified the ATLAS L1 display technique (Badge et al., Am J Hum Genet 72(4):823-838, 2003) to investigate de novo L1 retrotransposition in human genomes. In this chapter, we describe how we combined a high-coverage ATLAS variant with high-throughput sequencing, achieving 11-25* sequence depth per single amplicon, to study L1 retrotransposition in whole genome amplified (WGA) DNAs. PMID- 26895049 TI - RNA-Seq Analysis to Measure the Expression of SINE Retroelements. AB - The intrinsic features of retroelements, like their repetitive nature and disseminated presence in their host genomes, demand the use of advanced methodologies for their bioinformatic and functional study. The short length of SINE (short interspersed elements) retrotransposons makes such analyses even more complex. Next-generation sequencing (NGS) technologies are currently one of the most widely used tools to characterize the whole repertoire of gene expression in a specific tissue. In this chapter, we will review the molecular and computational methods needed to perform NGS analyses on SINE elements. We will also describe new methods of potential interest for researchers studying repetitive elements. We intend to outline the general ideas behind the computational analyses of NGS data obtained from SINE elements, and to stimulate other scientists to expand our current knowledge on SINE biology using RNA-seq and other NGS tools. PMID- 26895050 TI - Qualitative and Quantitative Assays of Transposition and Homologous Recombination of the Retrotransposon Tf1 in Schizosaccharomyces pombe. AB - Transposition and homologous recombination assays are valuable genetic tools to measure the production and integration of cDNA from the long terminal repeat (LTR) retrotransposon Tf1 in the fission yeast (Schizosaccharomyces pombe). Here we describe two genetic assays, one that measures the transposition activity of Tf1 by monitoring the mobility of a drug resistance marked Tf1 element expressed from a multi-copy plasmid and another assay that measures homologous recombination between Tf1 cDNA and the expression plasmid. While the transposition assay measures insertion of full-length Tf1 cDNA mediated by the transposon integrase, the homologous recombination assay measures levels of cDNA present in the nucleus and is independent of integrase activity. Combined, these assays can be used to systematically screen large collections of strains to identify mutations that specifically inhibit the integration step in the retroelement life cycle. Such mutations can be identified because they reduce transposition activity but nevertheless have wild-type frequencies of homologous recombination. Qualitative assays of yeast patches on agar plates detect large defects in integration and recombination, while the quantitative approach provides a precise method of determining integration and recombination frequencies. PMID- 26895051 TI - LINE Retrotransposition Assays in Saccharomyces cerevisiae. AB - Long interspersed nuclear element (LINE) retrotransposons make up significant parts of mammalian genomes. They alter host genomes by direct mutagenesis through integration of new transposon copies, by mobilizing non-autonomous transposons, by changes in host gene activity due to newly integrated transposons and by recombination events between different transposon copies. As a consequence, LINEs can contribute to genetic disease. Simple model systems can be useful for the study of basic molecular and cellular biology of LINE retrotransposons. Here, we describe methods for the analysis of LINE retrotransposition in the well established model organism Saccharomyces cerevisiae. The ability to follow retrotransposition in budding yeast opens up the possibility of performing systematic screens for evolutionarily conserved interactions between LINE retrotransposons and their host cells. PMID- 26895053 TI - L1 Retrotransposition in Neural Progenitor Cells. AB - Long interspersed nucleotide element 1 (LINE-1 or L1) is a family of non-LTR retrotransposons that can replicate and reintegrate into the host genome. L1s have considerably influenced mammalian genome evolution by retrotransposing during germ cell development or early embryogenesis, leading to massive genome expansion. For many years, L1 retrotransposons were viewed as a selfish DNA parasite that had no contribution in somatic cells. Historically, L1s were thought to only retrotranspose during gametogenesis and in neoplastic processes, but recent studies have shown that L1s are extremely active in the mouse, rat, and human neuronal progenitor cells (NPCs). These de novo L1 insertions can impact neuronal transcriptional expression, creating unique transcriptomes of individual neurons, possibly contributing to the uniqueness of the individual cognition and mental disorders in humans. PMID- 26895054 TI - Characterization of Engineered L1 Retrotransposition Events: The Recovery Method. AB - Long Interspersed Element class 1 retrotransposons (LINE-1 or L1) are abundant Transposable Elements in mammalian genomes and their mobility continues to impact the human genome. The development of engineered retrotransposition assays has been instrumental to understand how these elements are regulated and to identify domains involved in the process of retrotransposition. Additionally, the modification of a retrotransposition indicator cassette has allowed developing straightforward approaches to characterize the site of new L1 insertions in cultured cells. In this chapter, we describe a method termed "L1-recovery" that has been used to characterize the site of insertion on engineered L1 retrotransposition events in cultured mammalian cells. Notably, the recovery assay is based on a genetic strategy and avoids the use of PCR and thus reduces to a minimum the appearance of false positives/artifacts. PMID- 26895052 TI - LINE-1 Cultured Cell Retrotransposition Assay. AB - The Long INterspersed Element-1 (LINE-1 or L1) retrotransposition assay has facilitated the discovery and characterization of active (i.e., retrotransposition-competent) LINE-1 sequences from mammalian genomes. In this assay, an engineered LINE-1 containing a retrotransposition reporter cassette is transiently transfected into a cultured cell line. Expression of the reporter cassette, which occurs only after a successful round of retrotransposition, allows the detection and quantification of the LINE-1 retrotransposition efficiency. This assay has yielded insight into the mechanism of LINE-1 retrotransposition. It also has provided a greater understanding of how the cell regulates LINE-1 retrotransposition and how LINE-1 retrotransposition impacts the structure of mammalian genomes. Below, we provide a brief introduction to LINE-1 biology and then detail how the LINE-1 retrotransposition assay is performed in cultured mammalian cells. PMID- 26895055 TI - SINE Retrotransposition: Evaluation of Alu Activity and Recovery of De Novo Inserts. AB - Mobile element activity is of great interest due to its impact on genomes. However, the types of mobile elements that inhabit any given genome are remarkably varied. Among the different varieties of mobile elements, the Short Interspersed Elements (SINEs) populate many genomes, including many mammalian species. Although SINEs are parasites of Long Interspersed Elements (LINEs), SINEs have been highly successful in both the primate and rodent genomes. When comparing copy numbers in mammals, SINEs have been vastly more successful than other nonautonomous elements, such as the retropseudogenes and SVA. Interestingly, in the human genome the copy number of Alu (a primate SINE) outnumbers LINE-1 (L1) copies 2 to 1. Estimates suggest that the retrotransposition rate for Alu is tenfold higher than LINE-1 with about 1 insert in every twenty births. Furthermore, Alu-induced mutagenesis is responsible for the majority of the documented instances of human retroelement insertion-induced disease. However, little is known on what contributes to these observed differences between SINEs and LINEs. The development of an assay to monitor SINE retrotransposition in culture has become an important tool for the elucidation of some of these differences. In this chapter, we present details of the SINE retrotransposition assay and the recovery of de novo inserts. We also focus on the nuances that are unique to the SINE assay. PMID- 26895056 TI - The Engineered SVA Trans-mobilization Assay. AB - Mammalian genomes harbor autonomous retrotransposons coding for the proteins required for their own mobilization, and nonautonomous retrotransposons, such as the human SVA element, which are transcribed but do not have any coding capacity. Mobilization of nonautonomous retrotransposons depends on the recruitment of the protein machinery encoded by autonomous retrotransposons. Here, we summarize the experimental details of SVA trans-mobilization assays which address multiple questions regarding the biology of both nonautonomous SVA elements and autonomous LINE-1 (L1) retrotransposons. The assay evaluates if and to what extent a noncoding SVA element is mobilized in trans by the L1-encoded protein machinery, the structural organization of the resulting marked de novo insertions, if they mimic endogenous SVA insertions and what the roles of individual domains of the nonautonomous retrotransposon for SVA mobilization are. Furthermore, the highly sensitive trans-mobilization assay can be used to verify the presence of otherwise barely detectable endogenously expressed functional L1 proteins via their marked SVA trans-mobilizing activity. PMID- 26895057 TI - Detection of LINE-1 RNAs by Northern Blot. AB - Repetitive genetic elements have had an unprecedented success populating phylogenetically diverse species making them a common feature of most genomes. Hundreds of thousands of copies of active and non-functional transposable elements representing different classes and families can reside within and outside of host genes. In addition to creating structural variations in genomic DNA, some of these loci are expressed to contribute to the continuing amplification cycle. Transposable elements, specifically Long Interspersed Element-1 (LINE-1) produce a spectrum of RNAs, some of which are important for their mobilization, while others are processed forms of LINE-1 transcription that may or may not play relevant functions. Additionally, many LINE-1 sequences integrated into cellular genes are included into cellular transcripts creating substantial background when L1-related RNA expression is detected by some conventional methods. This chapter provides an in-depth description of the complexity of L1-generated mRNAs as well as sources of cellular transcripts containing L1 sequences. It also highlights the strengths and weaknesses of conventional methods used to detect LINE-1 expression. PMID- 26895058 TI - Monitoring Long Interspersed Nuclear Element 1 Expression During Mouse Embryonic Stem Cell Differentiation. AB - Long Interspersed Elements-1 (LINE-1 or L1) are a class of transposable elements which account for almost 19 % of the mouse genome. This represents around 600,000 L1 fragments, among which it is estimated that 3000 intact copies still remain capable to retrotranspose and to generate deleterious mutation by insertion into genomic coding region. In differentiated cells, full length L1 are transcriptionally repressed by DNA methylation. However at the blastocyst stage, L1 elements are subject to a demethylation wave and able to be expressed and to be inserted into new genomic locations. Mouse Embryonic Stem Cells (mESCs) are pluripotent stem cells derived from the inner cell mass of blastocysts. Mouse ESCs can be maintained undifferentiated under controlled culture conditions or induced into the three primary germ layers, therefore they represent a suitable model to follow mechanisms involved in L1 repression during the process of differentiation of mESCs. This protocol presents how to maintain culture of undifferentiated mESCs, induce their differentiation, and monitor L1 expression at the transcriptional and translational levels. L1 transcriptional levels are assessed by real-time qRT-PCR performed on total RNA extracts using specific L1 primers and translation levels are measured by Western blot analysis of L1 protein ORF1 using a specific L1 antibody. PMID- 26895059 TI - Immunodetection of Human LINE-1 Expression in Cultured Cells and Human Tissues. AB - Long interspersed element-1 (LINE-1) is the only active protein-coding retrotransposon in humans. It is not expressed in somatic tissue but is aberrantly expressed in a wide variety of human cancers. ORF1p protein is the most robust indicator of LINE-1 expression; the protein accumulates in large quantities in cellular cytoplasm. Recently, monoclonal antibodies have allowed more complete characterizations of ORF1p expression and indicated potential for developing ORF1p as a clinical biomarker. Here, we describe a mouse monoclonal antibody specific for human LINE-1 ORF1p and its application in immunofluorescence and immunohistochemistry of both cells and human tissues. We also describe detection of tagged LINE-1 ORF2p via immunofluorescence. These general methods may be readily adapted to use with many other proteins and antibodies. PMID- 26895060 TI - Cellular Localization of Engineered Human LINE-1 RNA and Proteins. AB - The human LINE-1 retrotransposon has the ability to mobilize into a new genomic location through an intracellular replication cycle. Immunofluorescence and in situ hybridization experiments have been developed to detect subcellular localization of retrotransposition intermediates (i.e., ORF1p, ORF2p, and L1 mRNA). Currently, these protocols are also used to validate the interaction between retrotransposition complex components and potential cellular partners involved in L1 replication. Here, we describe in details methods for the identification of LINE-1 proteins and/or RNA in cells transfected with vectors expressing engineered human LINE-1 elements. PMID- 26895061 TI - Purification of L1-Ribonucleoprotein Particles (L1-RNPs) from Cultured Human Cells. AB - Almost two-thirds of the human genome is repetitive DNA, mostly derived from different kinds of transposon and retrotransposon sequences. Although most of these sequences are stable in the genome, one class called long interspersed element (LINE1 or L1) is actively jumping in the human genome, particularly in brain, germ cells, and certain types of cancer. Recent estimates predict that L1 activity combined with L1-mediated activity is responsible for a new insertion in 1 out of 25 newborns. In humans, more than 100 single-gene disease cases have been reported due to L1 activity. An active L1 encodes two proteins designated as ORF1p and ORF2p. L1 jumps by a target primed reverse transcription (TPRT) mechanism where L1 RNA forms L1-RNPs after binding with L1 proteins. L1-RNPs then enter into the nucleus where L1 RNA is converted to cDNA at the site of integration which subsequently integrates into the genome with the help of the L1 proteins (ORF1p and ORF2p) and other cellular factors. Although L1 is continuously jumping in the human genome the basic mechanism and requirement of other cellular factors in L1 retrotransposition are relatively unknown due to the difficulty in purifying intact L1-RNPs. Here we describe a detailed protocol for purification of L1-RNPs by an immunoaffinity method. PMID- 26895064 TI - Biochemical Approaches to Study LINE-1 Reverse Transcriptase Activity In Vitro. AB - In vitro reverse transcriptase assays have been developed to monitor the presence and activity of ORF2p, an essential protein product of the LINE-1 retrotransposon (L1), in cellular fractions. We describe methods for expression and isolation of L1 ribonucleoprotein particles, and identification of ORF2p reverse transcriptase activity. Two independent methods are described: L1 element amplification protocol (LEAP) and direct L1 extension assay (DLEA). The first method involves cDNA synthesis by primer extension using dNTPs followed by a step of PCR amplification. The second method involves primer extension by incorporation of radiolabeled dTMPs followed by dot-blot or gel separation detection. Finally, we discuss the output and benefits of the two methods. PMID- 26895062 TI - Characterization of L1-Ribonucleoprotein Particles. AB - The LINE-1 retrotransposon (L1) encodes two proteins, ORF1p and ORF2p, which bind to the L1 RNA in cis, forming a ribonucleoprotein (RNP) complex that is critical for retrotransposition. Interactions with both permissive and repressive host factors pervade every step of the L1 life cycle. Until recently, limitations in detection and production precluded in-depth characterization of L1 RNPs. Inducible expression and recombinant engineering of epitope tags have made detection of both L1 ORFs routine. Here, we describe large-scale production of L1 expressing HEK-293T cells in suspension cell culture, cryomilling and affinity capture of L1 RNP complexes, sample preparation for analysis by mass spectrometry, and assay using the L1 element amplification protocol (LEAP) and qRT-PCR. PMID- 26895065 TI - Methylated DNA Immunoprecipitation Analysis of Mammalian Endogenous Retroviruses. AB - Endogenous retroviruses are repetitive sequences found abundantly in mammalian genomes which are capable of modulating host gene expression. Nevertheless, most endogenous retrovirus copies are under tight epigenetic control via histone repressive modifications and DNA methylation. Here we describe a common method used in our laboratory to detect, quantify, and compare mammalian endogenous retrovirus DNA methylation. More specifically we describe methylated DNA immunoprecipitation (MeDIP) followed by quantitative PCR. PMID- 26895063 TI - LEAP: L1 Element Amplification Protocol. AB - Long INterspersed Element-1 (LINE-1 or L1) retrotransposons encode two proteins (ORF1p and ORF2p) that are required for retrotransposition. The L1 element amplification protocol (LEAP) assays the ability of L1 ORF2p to reverse transcribe L1 RNA in vitro. Ultracentrifugation or immunoprecipitation is used to isolate L1 ribonucleoprotein particle (RNP) complexes from cultured human cells transfected with an engineered L1 expression construct. The isolated RNPs are incubated with an oligonucleotide that contains a unique sequence at its 5' end and a thymidine-rich sequence at its 3' end. The addition of dNTPs to the reaction allows L1 ORF2p bound to L1 RNA to generate L1 cDNA. The resultant L1 cDNAs then are amplified using polymerase chain reaction (PCR) and the products are visualized by gel electrophoresis. Sequencing the resultant PCR products then allows product verification. The LEAP assay has been instrumental in determining how mutations in L1 ORF1p and ORF2p affect L1 reverse transcriptase (RT) activity. Furthermore, the LEAP assay has revealed that the L1 ORF2p RT can extend a DNA primer with mismatched 3' terminal bases when it is annealed to an L1 RNA template. As the LINE-1 biology field gravitates toward studying cellular proteins that regulate LINE-1, molecular genetic and biochemical approaches such as LEAP, in conjunction with the LINE-1-cultured cell retrotransposition assay, are essential to dissect the molecular mechanism of L1 retrotransposition. PMID- 26895066 TI - Profiling DNA Methylation and Hydroxymethylation at Retrotransposable Elements. AB - DNA methylation is a key epigenetic modification controlling the transcriptional activity of mammalian retrotransposable elements. Its oxidation to DNA hydroxymethylation has been linked to DNA demethylation and reactivation of retrotransposons. Here we describe in detail protocols for three methods to measure DNA methylation and hydroxymethylation at specific genomic targets: glucMS-qPCR, and two sequencing approaches (pyrosequencing and high-throughput sequencing) for analyzing bisulfite- and oxidative bisulfite-modified DNA. All three techniques provide absolute measurements of methylation and hydroxymethylation levels at single-base resolution. Differences between the methods are discussed, mainly with respect to throughput and target coverage. These constitute the core techniques that are used in our laboratory for accurately surveying the epigenetics of retrotransposable elements. PMID- 26895067 TI - A Large-Scale Functional Screen to Identify Epigenetic Repressors of Retrotransposon Expression. AB - Deposition of epigenetic marks is an important layer of the transcriptional control of retrotransposons, especially during early embryogenesis. Kruppel associated box domain zinc finger proteins (KRAB-ZFPs) are one of the largest families of transcription factors, and collectively partake in this process by tethering to thousands of retroelement-containing genomic loci their cofactor KAP1, which acts as a scaffold for a heterochromatin-inducing machinery. However, while the sequence-specific DNA binding potential of the poly-zinc finger containing KRAB-ZFPs is recognized, very few members of the family have been assigned specific targets. In this chapter, we describe a large-scale functional screen to identify the retroelements bound by individual murine KRAB-ZFPs. Our method is based on the automated transfection of a library of mouse KRAB-ZFP containing vectors into 293T cells modified to express GFP from a PGK promoter harboring in its immediate vicinity a KAP1-recruiting retroelement-derived sequence. Analysis is then performed by plate reader and flow cytometry fluorescence readout. Such large-scale DNA-centered functional approach can not only help to identify the trans-acting factors responsible for silencing retrotransposons, but also serve as a model for dissecting the transcriptional networks influenced by retroelement-derived cis-acting sequences. PMID- 26895068 TI - Reprogramming of Human Fibroblasts to Induced Pluripotent Stem Cells with Sleeping Beauty Transposon-Based Stable Gene Delivery. AB - Human induced pluripotent stem (iPS) cells are a source of patient-specific pluripotent stem cells and resemble human embryonic stem (ES) cells in gene expression profiles, morphology, pluripotency, and in vitro differentiation potential. iPS cells are applied in disease modeling, drug screenings, toxicology screenings, and autologous cell therapy. In this protocol, we describe how to derive human iPS cells from fibroblasts by Sleeping Beauty (SB) transposon mediated gene transfer of reprogramming factors. First, the components of the non viral Sleeping Beauty transposon system, namely a transposon vector encoding reprogramming transcription factors and a helper plasmid expressing the SB transposase, are electroporated into human fibroblasts. The reprogramming cassette undergoes transposition from the transfected plasmids into the fibroblast genome, thereby resulting in stable delivery of the reprogramming factors. Reprogramming by using this protocol takes ~4 weeks, after which the iPS cells are isolated and clonally propagated. PMID- 26895069 TI - Anxiety and depression predict musculoskeletal disorders in health care workers. AB - Incidence of musculoskeletal disorders (MSDs) is high among health care workers (HCWs). To determine whether MSDs are associated with preexisting anxiety and/or depression, a case-control study was carried out in female HCWs (56 cases/55 controls). Cases were HCWs with a first-time clinical diagnosis of MSD within the previous 2 years. Occupation, workplace, work shift, direct patient assistance, and anxiety/depression scores (Goldberg scale) were assessed. Increased risk of incident MSDs (multivariate logistic regression) was found in workers with preexisting anxiety/depression compared to those without (OR 5.01; 95% CI 2.20 12.05; p < .01). Other significant risk factors were direct patient assistance (OR 2.59; 95% CI 1.03-6.92; p = .04) and morning work shift (OR 2.47; 95% CI 0.99 6.48; p = .05). Preexisting anxiety/depression was associated with incident MSDs in HCWs, adjusting for occupational exposure risk factors. PMID- 26895070 TI - Genomic variants in the ASS1 gene, involved in the nitric oxide biosynthesis and signaling pathway, predict hydroxyurea treatment efficacy in compound sickle cell disease/beta-thalassemia patients. AB - AIM: Hemoglobinopathies exhibit a remarkable phenotypic diversity that restricts any safe association between molecular pathology and clinical outcomes. PATIENTS & METHODS: Herein, we explored the role of genes involved in the nitric oxide biosynthesis and signaling pathway, implicated in the increase of fetal hemoglobin levels and response to hydroxyurea treatment, in 119 Hellenic patients with beta-type hemoglobinopathies. RESULTS: We show that two ASS1 genomic variants (namely, rs10901080 and rs10793902) can serve as pharmacogenomic biomarkers to predict hydroxyurea treatment efficacy in sickle cell disease/beta thalassemia compound heterozygous patients. CONCLUSION: These markers may exert their effect by inducing nitric oxide biosynthesis, either via altering splicing and/or miRNA binding, as predicted by in silico analysis, and ultimately, increase gamma-globin levels, via guanylyl cyclase targeting. PMID- 26895071 TI - Repeat Cardiovascular Risk Assessment after Four Years: Is There Improvement in Risk Prediction? AB - BACKGROUND: Framingham risk equations are widely used to predict cardiovascular disease based on health information from a single time point. Little is known regarding use of information from repeat risk assessments and temporal change in estimated cardiovascular risk for prediction of future cardiovascular events. This study was aimed to compare the discrimination and risk reclassification of approaches using estimated cardiovascular risk at single and repeat risk assessments. METHODS: Using data on 12,197 individuals enrolled in EPIC-Norfolk cohort, with 12 years of follow-up, we examined rates of cardiovascular events by levels of estimated absolute risk (Framingham risk score) at the first and second health examination four years later. We calculated the area under the receiver operating characteristic curve (aROC) and risk reclassification, comparing approaches using information from single and repeat risk assessments (i.e., estimated risk at different time points). RESULTS: The mean Framingham risk score increased from 15.5% to 17.5% over a mean of 3.7 years from the first to second health examination. Individuals with high estimated risk (>=20%) at both health examinations had considerably higher rates of cardiovascular events than those who remained in the lowest risk category (<10%) in both health examinations (34.0 [95%CI 31.7-36.6] and 2.7 [2.2-3.3] per 1,000 person-years respectively). Using information from the most up-to-date risk assessment resulted in a small non significant change in risk classification over the previous risk assessment (net reclassification improvement of -4.8%, p>0.05). Using information from both risk assessments slightly improved discrimination compared to information from a single risk assessment (aROC 0.76 and 0.75 respectively, p<0.001). CONCLUSIONS: Using information from repeat risk assessments over a period of four years modestly improved prediction, compared to using data from a single risk assessment. However, this approach did not improve risk classification. PMID- 26895073 TI - The Drug Derived Complexity Index (DDCI) Predicts Mortality, Unplanned Hospitalization and Hospital Readmissions at the Population Level. AB - OBJECTIVE: to develop and validate the Drug Derived Complexity Index (DDCI), a predictive model derived from drug prescriptions able to stratify the general population according to the risk of death, unplanned hospital admission, and readmission, and to compare the new predictive index with the Charlson Comorbidity Index (CCI). DESIGN: Population-based cohort study, using a record linkage analysis of prescription databases, hospital discharge records, and the civil registry. The predictive model was developed based on prescription patterns indicative of chronic diseases, using a random sample of 50% of the population. Multivariate Cox proportional hazards regression was used to assess weights of different prescription patterns and drug classes. The predictive properties of the DDCI were confirmed in the validation cohort, represented by the other half of the population. The performance of DDCI was compared to the CCI in terms of calibration, discrimination and reclassification. SETTING: 6 local health authorities with 2.0 million citizens aged 40 years or above. RESULTS: One year and overall mortality rates, unplanned hospitalization rates and hospital readmission rates progressively increased with increasing DDCI score. In the overall population, the model including age, gender and DDCI showed a high performance. DDCI predicted 1-year mortality, overall mortality and unplanned hospitalization with an accuracy of 0.851, 0.835, and 0.584, respectively. If compared to CCI, DDCI showed discrimination and reclassification properties very similar to the CCI, and improved prediction when used in combination with the CCI. CONCLUSIONS AND RELEVANCE: DDCI is a reliable prognostic index, able to stratify the entire population into homogeneous risk groups. DDCI can represent an useful tool for risk-adjustment, policy planning, and the identification of patients needing a focused approach in everyday practice. PMID- 26895072 TI - Percutaneous Vaccination as an Effective Method of Delivery of MVA and MVA Vectored Vaccines. AB - The robustness of immune responses to an antigen could be dictated by the route of vaccine inoculation. Traditional smallpox vaccines, essentially vaccinia virus strains, that were used in the eradication of smallpox were administered by percutaneous inoculation (skin scarification). The modified vaccinia virus Ankara is licensed as a smallpox vaccine in Europe and Canada and currently undergoing clinical development in the United States. MVA is also being investigated as a vector for the delivery of heterologous genes for prophylactic or therapeutic immunization. Since MVA is replication-deficient, MVA and MVA-vectored vaccines are often inoculated through the intramuscular, intradermal or subcutaneous routes. Vaccine inoculation via the intramuscular, intradermal or subcutaneous routes requires the use of injection needles, and an estimated 10 to 20% of the population of the United States has needle phobia. Following an observation in our laboratory that a replication-deficient recombinant vaccinia virus derived from the New York City Board of Health strain elicited protective immune responses in a mouse model upon inoculation by tail scarification, we investigated whether MVA and MVA recombinants can elicit protective responses following percutaneous administration in mouse models. Our data suggest that MVA administered by percutaneous inoculation, elicited vaccinia-specific antibody responses, and protected mice from lethal vaccinia virus challenge, at levels comparable to or better than subcutaneous or intramuscular inoculation. High titers of specific neutralizing antibodies were elicited in mice inoculated with a recombinant MVA expressing the herpes simplex type 2 glycoprotein D after scarification. Similarly, a recombinant MVA expressing the hemagglutinin of attenuated influenza virus rgA/Viet Nam/1203/2004 (H5N1) elicited protective immune responses when administered at low doses by scarification. Taken together, our data suggest that MVA and MVA-vectored vaccines inoculated by scarification can elicit protective immune responses that are comparable to subcutaneous vaccination, and may allow for antigen sparing when vaccine supply is limited. PMID- 26895074 TI - Mismatch repair deficiency testing in clinical practice. AB - Lynch syndrome, an autosomal dominant inherited disorder, is caused by inactivating mutations involving DNA mismatch repair (MMR) genes. This leads to profound genetic instability, including microsatellite instability (MSI) and increased risk for cancer development, particularly colon and endometrial malignancies. Clinical testing of tumor tissues for the presence of MMR gene deficiency is standard practice in clinical oncology, with immunohistochemistry and PCR-based microsatellite instability analysis used as screening tests to identify potential Lynch syndrome families. The ultimate diagnosis of Lynch syndrome requires documentation of mutation within one of the four MMR genes (MLH1, PMS2, MSH2 and MSH6) or EPCAM, currently achieved by comprehensive sequencing analysis of germline DNA. In this review, the genetic basis of Lynch syndrome, methodologies of MMR deficiency testing, and current diagnostic algorithms in the clinical management of Lynch syndrome, are discussed. PMID- 26895075 TI - Exchange Coupling of Spin-Crossover Molecules to Ferromagnetic Co Islands. AB - The properties of Fe(1,10-phenanthroline)2(NCS)2 (Fe-phen) molecules deposited on Co/Cu(111) are studied with scanning tunneling microscopy (STM) operated in ultrahigh vacuum at low temperature (4 K) and ab initio calculations. Both the experimental and theoretical results are used to identify the high-spin (HS) state of Fe-phen. Additionally, the calculations reveal a strong spin polarization of the density of states (DOS) and is validated experimentally using the spin sensitivity of spin-polarized STM. Finally, it is shown that the magnetic moment of the Fe-ion within HS Fe-phen is strongly magnetically coupled to the underlying magnetic Co through the NCS groups. These findings enable promising spintronic perspectives. PMID- 26895078 TI - Correlations between Structural and Electronic Properties in the Filled Skutterudite Smy(FexNi1-x)4Sb12. AB - A structural study of the filled skutterudite Smy(FexNi1-x)4Sb12 was performed by means of X-ray powder diffraction and MU-Raman spectroscopy with the aim to unveil the correlations between structural and electronic properties of this material and to favor the improvement of its thermoelectric performance. Samples were prepared by direct reaction of the elements at 1223 K, followed by quenching and subsequent sintering at 873 K; microstructure and composition of the obtained products were determined by SEM-EDS. The position of the boundary separating regions that obey hole- and electron-based conduction mechanisms was found by X ray diffraction at x ~ 0.63 and y ~ 0.30, confirmed by measurements of room temperature Seebeck coefficient, and discussed on the basis of crystallographic data. The presence of a discontinuity is observed in several structural and spectroscopic parameters at the p/n crossover; it is interpreted as associated with the change in the conduction mechanism. The role of the rare earth filling fraction in driving the structural response of the material is investigated too. The advantage of using X-ray diffraction and MU-Raman spectroscopy as aids in the study of electronic properties of this material is highlighted, as well as the complementarity of the two techniques. PMID- 26895077 TI - Valence fluctuations of europium in the boride Eu4Pd(29+x)B8. AB - We synthesized a high-quality sample of the boride Eu4Pd(29+x)B8 (x = 0.76) and studied its structural and physical properties. Its tetragonal structure was solved by direct methods and confirmed to belong to the Eu4Pd29B8 type. All studied physical properties indicate a valence fluctuating Eu state, with a valence decreasing continuously from about 2.9 at 5 K to 2.7 at 300 K. Maxima in the T dependence of the susceptibility and thermopower at around 135 K and 120 K, respectively, indicate a valence fluctuation energy scale on the order of 300 K. Analysis of the magnetic susceptibility evidences some inconsistencies when using the ionic interconfigurational fluctuation (ICF) model, thus suggesting a stronger relevance of hybridization between 4f and valence electrons compared to standard valence-fluctuating Eu systems. PMID- 26895076 TI - Fatigue in Multiple Sclerosis: Assessing Pontine Involvement Using Proton MR Spectroscopic Imaging. AB - BACKGROUND/OBJECTIVE: The underlying mechanism of fatigue in multiple sclerosis (MS) remains poorly understood. Our study investigates the involvement of the ascending reticular activating system (ARAS), originating in the pontine brainstem, in MS patients with symptoms of fatigue. METHODS: Female relapsing remitting MS patients (n = 17) and controls (n = 15) underwent a magnetic resonance spectroscopic imaging protocol at 1.5T. Fatigue was assessed in every subject using the Fatigue Severity Scale (FSS). Using an FSS cut-off of 36, patients were categorized into a low (n = 9, 22 +/- 10) or high (n = 10, 52 +/- 6) fatigue group. The brain metabolites N-acetylaspartate (NAA) and total creatine (tCr) were measured from sixteen 5x5x10 mm3 spectroscopic imaging voxels in the rostral pons. RESULTS: MS patients with high fatigue had lower NAA/tCr concentration in the tegmental pons compared to control subjects. By using NAA and Cr values in the cerebellum for comparison, these NAA/tCr changes in the pons were driven by higher tCr concentration, and that these changes were focused in the WM regions. DISCUSSION/CONCLUSION: Since there were no changes in NAA concentration, the increase in tCr may be suggestive of gliosis, or an imbalanced equilibrium of the creatine and phosphocreatine ratio in the pons of relapsing remitting MS patients with fatigue. PMID- 26895080 TI - An integrated analysis of the efficacy and safety of desvenlafaxine in the treatment of major depressive disorder. AB - The chronic course of major depressive disorder (MDD) often impedes the ability of patients to achieve full remission. Return of full functioning is a critical goal of antidepressant pharmacotherapy as the presence of residual depressive symptoms is associated with an increased risk of relapse. Treatment guidelines recommend selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, or atypical antidepressants as first-line treatment for moderate to severe MDD. Desvenlafaxine, administered as desvenlafaxine succinate, is an serotonin-norepinephrine reuptake inhibitor approved for the treatment of adults with MDD at the recommended dose of 50 mg/day. The aim of this integrated analysis was to assess the efficacy and safety of desvenlafaxine 50 and 100 mg/day compared with placebo in adult outpatients with MDD. The analysis used data from nine fixed-dose, short-term, placebo-controlled studies in adult outpatients diagnosed with MDD who had depressive symptoms for at least 30 days. Data from 4279 and 4317 patients were pooled for the efficacy and safety analyses, respectively. Statistically significant improvements were observed with desvenlafaxine 50 and 100 mg/day versus placebo for all efficacy endpoints assessed, including improvements in depressive symptoms, response and remission rates, as well as functional and cognitive outcomes. Treatment with desvenlafaxine 50 and 100 mg/day was generally safe and well tolerated. The findings of this integrated analysis of data from a large population of patients with MDD confirmed the antidepressant efficacy of both desvenlafaxine doses and add to previous evidence supporting the efficacy of desvenlafaxine. PMID- 26895081 TI - Nacre-inspired integrated strong and tough reduced graphene oxide-poly(acrylic acid) nanocomposites. AB - Inspired by the relationship between interface interactions and the high performance mechanical properties of nacre, a strong and tough nacre-inspired nanocomposite was demonstrated based on graphene oxide (GO) and polyacrylic acid (PAA) prepared via a vacuum-assisted filtration self-assembly process. The abundant hydrogen bonding between GO and PAA results in both high strength and toughness of the bioinspired nanocomposites, which are 2 and 3.3 times higher than that of pure reduced GO film, respectively. In addition, the effect of environmental relative humidity on the mechanical properties of bioinspired nanocomposites is also investigated, and is consistent with previous theoretical predictions. Moreover, this nacre-inspired nanocomposite also displays high electrical conductivity of 108.9 S cm(-1). These excellent physical properties allow this type of nacre-inspired nanocomposite to be used in many applications, such as flexible electrodes, aerospace applications, and artificial muscles etc. This nacre-inspired strategy also opens an avenue for constructing integrated high performance graphene-based nanocomposites in the near future. PMID- 26895082 TI - Reduction-Induced Highly Selective Uptake of Cesium Ions by an Ionic Crystal Based on Silicododecamolybdate. AB - Cation adsorption and exchange has been an important topic in both basic and applied chemistry relevant to materials synthesis and chemical conversion, as well as purification and separation. Selective Cs(+) uptake from aqueous solutions is especially important because Cs(+) is expensive and is contained in radioactive wastes. However, the reported adsorbents incorporate Rb(+) as well as Cs(+) , and an adsorbent with high selectivity toward Cs(+) has not yet been reported. Highly selective uptake of Cs(+) by an ionic crystal (etpyH)2 [Cr3O(OOCH)6 (etpy)3]2 [alpha-SiMo12 O40 ]?3 H2O (etpy =4-ethylpyridine) is described. The compound incorporated up to 3.8 mol(Cs(+) ) mol(s)(-1) (where s=solid) by cation-exchange with etpyH(+) and reduction of silicododecamolybdate with ascorbic acid. The amount of Cs(+) uptake was comparable to that of Prussian blue, which is widely recognized as a good Cs(+) adsorbent. Moreover, other alkali-metal and alkaline-earth-metal cations were almost completely excluded (<0.2 mol mol(s)(-1)). PMID- 26895083 TI - Retrograde Intrarenal Surgery is equally efficient and safe in patients with different American Society of Anesthesia physical status. AB - OBJECTIVE: To assess the efficacy and safety of Retrograde Intrarenal Surgery to treat renal stones in patients with different American Society of Anesthesia (ASA) physical status. MATERIAL AND METHODS: We performed a retrospective analysis of 150 patients who underwent Retrograde Intrarenal Surgery for renal stone between October 2013 and December 2014. Patients were categorized into three groups according to their ASA physical status: ASA Class 1 (Group 1, n = 23), ASA Class 2 (Group 2, n = 113) and ASA Class 3 (Group 3, n = 14). We documented and stratified the per-operative and postoperative complications according to modified Satava Classification System and Clavien-Dindo Classification. RESULTS: The mean age of the patients was 44 years. The total stone-free rate was 81.2%. According to the groups, the stone-free rate was 75% in Group 1, 82.5% in Group 2, and 83.3% in Group 3 (p = 0.340). Per-operative and postoperative complications were recorded in 12% (n = 18) and 5.3% (n = 8) of the patients. We did not find significant difference in terms of per-operative and postoperative complication rates among patients with different ASA physical status (p(per-operative) = 0.392 and p(postoperative) = 0.136). CONCLUSIONS: Retrograde Intrarenal Surgery is an effective and safe surgery with high stone free rates and low morbidity in patients with different ASA physical status. PMID- 26895084 TI - Human papillomavirus not detected in esophageal adenocarcinoma tumor specimens. AB - BACKGROUND: Human papillomavirus (HPV) has been implicated as playing a causal role in Barrett's esophagus, the metaplastic precursor to esophageal adenocarcinomas (EAC) and gastro-esophageal junction adenocarcinomas (GEJACs). We evaluated the presence of HPV DNA in EACs and GEJACs. STUDY DESIGN: We analyzed 241 histologically confirmed archived EAC and GEJAC tissue specimens from a population-based study in Australia. Samples were tested by PCR for DNA quality (beta-globin) and for the presence of HPV DNA. RESULTS: DNA yield and quality was satisfactory in 97% (233/241; 201 EAC, 32 GEJAC). Each sample was tested three times for HPV DNA, but none of the 233 tumor specimens tested positive. CONCLUSIONS: We found no evidence of HPV DNA in esophageal adenocarcinoma tumor cells. HPV is unlikely to cause EAC or GEJAC. PMID- 26895085 TI - Colorectal cancer prevention and intentions to use low-dose aspirin: A survey of 1000 U.S. adults aged 40-65. AB - OBJECTIVE: The Translating Research into Action (TRIA) study was initiated to gather dissemination information on emerging cancer control recommendations. Daily, low-dose aspirin has been identified as a promising means of preventing colorectal cancer, and stakeholders are already calling for research to facilitate dissemination. Thus, the current study sought to identify factors related to intention to use aspirin for colorectal cancer prevention. METHODS: In April 2014, U.S. adults aged 40-65 (N=1000) were recruited to participate in a survey grounded in the health belief model. RESULTS: Older, Black males were more likely to intend to use low-dose aspirin to prevent colorectal cancer. Smokers, and those with a history of polyps, were also more receptive to initiating daily, low-dose aspirin use. Five psychosocial factors were related to intention including self-efficacy, response efficacy, perceived barriers, perceived susceptibility to colorectal cancer, and cancer information overload. CONCLUSION: Initial campaigns/interventions designed to increase daily, low-dose aspirin for colorectal cancer prevention may be more effective if they target receptive populations (older, Black males) using messages informed by the health belief model. PMID- 26895086 TI - Retinoid-related orphan receptor gamma t (RORgammat) inhibitors from Vitae Pharmaceuticals (WO2015116904) and structure proposal for their Phase I candidate VTP-43742. AB - Retinoic acid receptor-related orphan nuclear receptor gamma t (RORgammat or RORC2) is a key transcription factor for the differentiation of naive proinflammatory CD4(+) T cells and the production of T helper-17 (TH17) cells. Inhibiting RORgammat activity is thought to be beneficial in targeting a variety of inflammatory and autoimmune disorders, however current candidates remain to be validated in the clinic. Recently Vitae Pharmaceuticals successfully finished its Phase 1 single ascending dose clinical study with their proprietary RORgammat inverse agonist VTP-43742. On the basis of the reported promising results, Vitae Pharmaceuticals could currently be considered as having the leading clinical candidate in the RORgammat inverse agonist category. This prompts the interest on the exact chemical structure of their clinical candidate. The first relevant patent application (WO2014179564) from Vitae Pharmaceuticals describes RORgammat inverse agonists with a 5,6-dihydro-4H-pyrrolo[3,4-d]thiazole core, while in the second and latest patent application (WO2015116904) this element has changed towards a 6,7-dihydro-5H-pyrrolo[3,4-b]pyridine core. By combining information from Vitae's patent applications and trustworthy online information, the potential elucidation of the chemical structure of clinical candidate VTP-43742 is described. PMID- 26895088 TI - A prospective study of platelet function in trauma patients. AB - BACKGROUND: Exsanguination associated with acute traumatic coagulopathy is a leading cause of death following injury. While platelets occupy a pivotal role in clot formation, clinical research has been scant because of complexities resulting from the need for rapid handling and complex testing of platelet functions. While the thrombin pathway has been proposed as a mediator of platelet dysfunction in trauma, it has not been systematically investigated. The purpose of this study was to evaluate the thrombin pathway in platelet dysfunction. METHODS: Forty trauma patients and 20 noninjured controls were enrolled in the study at a Level I trauma center. Platelet aggregation was tested by light transmission aggregometry with two agonists, adenosine diphosphate (ADP) and thrombin receptor agonist peptide (TRAP). Mean fluorescence intensity and percent positivity of CD62 on ADP-activated platelets were evaluated using flow cytometry. Enzyme-linked immunosorbent assays were performed to evaluate the concentrations of D-dimer, thrombin-antithrombin complex (TAT), and prothrombin fragment 1 + 2 (PF 1 + 2) in each sample. RESULTS: Compared with healthy controls, trauma patients had significantly decreased ADP- and TRAP-mediated platelet aggregation and ADP-mediated CD62 expression. In trauma patients, TRAP mediated aggregation was inversely proportional to head Abbreviated Injury Scale (AIS) score. Glasgow Coma Scale (GCS) score was directly proportional to TRAP- and ADP-mediated aggregation. When compared with controls, significant differences of D-dimer, TAT, and PF 1 + 2 were found. Measures of shock, including admission blood pressure, pulse, base deficit, and lactate level, did not correlate with platelet dysfunction. CONCLUSION: Trauma patients have significantly lower levels of platelet activation and aggregation compared with healthy controls. Severity of head injury was significantly correlated with platelet dysfunction in a stepwise fashion. Trauma patients also have significantly increased levels of D-dimer, TAT, and PF 1 + 2 when compared with healthy controls. Our data suggest that the thrombin receptor pathway plays an important role in platelet dysfunction in trauma. LEVEL OF EVIDENCE: Prognostic and epidemiologic study, level III. PMID- 26895089 TI - Use of CPR in hemorrhagic shock, a dog model. AB - INTRODUCTION: Cardiopulmonary resuscitation was designed for sudden cardiac events usually triggered by thrombotic phenomena. Despite this, it is routinely used in trauma resuscitations as per the American Heart guidelines. There is no data supporting the use of chest compressions in hemorrhagic shock. An evidence based cardiopulmonary resuscitation (CPR) protocol has been developed for dogs. We sought to determine the effects and outcomes of chest compressions in hemorrhagic shock in a canine model. METHODS: Eighteen dogs were randomized to three treatment groups-chest compressions only after hemorrhagic shock (CPR), CPR with fluid resuscitation after hemorrhagic shock (CPR + FLU), and fluid resuscitation alone after hemorrhagic shock (FLU). Under anesthesia, dogs were hemorrhaged until pulse was lost; they were maintained pulseless for 30 minutes and then resuscitated over 20 minutes. Vital signs and laboratory values were recorded at determined intervals. Echocardiography was performed throughout the study. Upon termination of the study, kidney, liver, heart, and brain tissue histology was evaluated for end organ damage. Statistical significance was p < 0.05 with a Bonferroni correction for multiple comparisons. RESULTS: Blood loss and mean time to loss of pulse were similar between the groups. Dogs in the CPR group had significantly lower mean arterial pressure and higher pulse at all points compared to CPR + FLU and FLU (p < 0.05). Ejection fraction was lower in the CPR group at 5 and 10 minutes compared to the other groups (p < 0.05). Vital signs and laboratory results between CPR + FLU and FLU were equivalent. Two of six dogs in the CPR group died, while no dogs died in the CPR + FLU or FLU groups. Dogs in the CPR group were found to have more episodes of end organ damage. CONCLUSION: There was no benefit to chest compressions in the hypovolemic animals. Chest compressions in addition to fluid did not reverse signs of shock better than fluid alone. Further research is needed to define if there is a role of CPR in the trauma patient with hemorrhagic shock. PMID- 26895087 TI - Stepwise nucleosome translocation by RSC remodeling complexes. AB - The SWI/SNF-family remodelers regulate chromatin structure by coupling the free energy from ATP hydrolysis to the repositioning and restructuring of nucleosomes, but how the ATPase activity of these enzymes drives the motion of DNA across the nucleosome remains unclear. Here, we used single-molecule FRET to monitor the remodeling of mononucleosomes by the yeast SWI/SNF remodeler, RSC. We observed that RSC primarily translocates DNA around the nucleosome without substantial displacement of the H2A-H2B dimer. At the sites where DNA enters and exits the nucleosome, the DNA moves largely along or near its canonical wrapping path. The translocation of DNA occurs in a stepwise manner, and at both sites where DNA enters and exits the nucleosome, the step size distributions exhibit a peak at approximately 1-2 bp. These results suggest that the movement of DNA across the nucleosome is likely coupled directly to DNA translocation by the ATPase at its binding site inside the nucleosome. PMID- 26895090 TI - Associations between eating disorder symptoms and suicidal ideation through thwarted belongingness and perceived burdensomeness among eating disorder patients. AB - BACKGROUND: Suicidal ideation is relatively common among people with eating disorders (EDs). The Interpersonal-Psychological Theory of Suicide holds that suicidal ideation has two proximal causes: thwarted belongingness and perceived burdensomeness. It is unknown which ED symptoms are positively associated with suicidal ideation, and whether thwarted belongingness and perceived burdensomeness explain those associations. METHOD: We tested two parallel mediation models to determine whether current and lifetime ED symptoms were positively related to suicidal ideation through thwarted belongingness and perceived burdensomeness among ED patients (n=98), controlling for current depression. In each model, ED symptoms and depression were predictors, thwarted belongingness and perceived burdensomeness were mediators, and suicidal ideation was the outcome. RESULTS: The first model included current symptoms; current body dissatisfaction (ab=0.04, 95% CI [0.01, 0.06]) and fasting (ab=0.12, 95% CI [0.01, 0.22]) were indirectly related to increased suicidal ideation through higher burdensomeness, controlling for depression. The second model included lifetime symptoms; lifetime fasting (ab=0.18, 95% CI [0.07, 0.29]) was indirectly related to increased suicidal ideation through higher burdensomeness, controlling for depression. LIMITATIONS: The sample size prevented the use of latent variables for thwarted belongingness and perceived burdensomeness, and the cross sectional data prevented testing for bidirectional relations among ED symptoms, thwarted belongingness, perceived burdensomeness, and suicidal ideation. CONCLUSIONS: Results underscore the importance of exploring transdiagnostic ED symptoms, including body dissatisfaction and fasting in particular, that may intensify burdensomeness and thereby contribute to suicidal ideation over and above depressive symptoms in this high-risk population. PMID- 26895091 TI - Prospective relationship of depressive symptoms, drinking, and tobacco smoking among middle-aged and elderly community-dwelling adults: Results from the China Health and Retirement Longitudinal Study (CHARLS). AB - BACKGROUND: Previous studies in Western countries have consistently documented positive associations of smoking and heavy drinking with depressive symptoms but a prospective analysis of these relationships among middle-aged and elderly community members in China have not previously been reported. METHODS: Using data from the China Health and Retirement Longitudinal Study, a two-wave nationally representative survey conducted in 15,628 adults 45 years of age and older, we estimated the prospective association between depressive symptoms and an array of smoking and drinking behaviors. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D) short form. RESULTS: Inverse associations were the dominant pattern of association. For the population as a whole, individuals with baseline depressive symptoms were less likely to start drinking (OR=0.7, 95% CI=0.5, 0.9) or smoking (OR=0.6, 95% CI=0.4, 0.8). Similarly, baseline drinkers and smokers were less likely to develop depressive symptoms (ORdrinkers=0.6, 95% CI=0.5, 0.7; ORsmokers=0.7, 95% CJ=0.6, 0.9). No evidence was found for an increased incidence or persistence of depressive symptoms among high-frequency drinkers or heavy smokers or vice versa. Males who had never smoked prior to the onset of depressive symptoms tended to have more rapid onset of tobacco dependence compared to those without such symptoms. Males and females had different association patterns. LIMITATIONS: The study is observational in nature and provides limited evidence for causality. DISCUSSION: The results are inconsistent with previous findings in Western countries, throwing into question the presumed universality of the association between alcohol drinking or tobacco use and depression among middle-aged and elderly adults. PMID- 26895092 TI - Autistic traits and empathy in chronic vs. episodic depression. AB - OBJECTIVES: Difficulties in social interaction are characteristic for depressive disorders and one of the cardinal symptoms of Autism Spectrum Disorders (ASD). It has been proposed that chronically depressed persons have profoundly impaired empathic abilities in comparison to episodically depressed persons, and that specifically they exhibit a deficit in cognitive empathy, but not in affective empathy, a pattern also reported in ASD. This study aimed to explore autistic traits and empathy deficits in chronic depression, and identify specific differences to episodic depression. METHOD: Autistic traits and multimodal empathy were assessed in chronically depressed patients (n=59), episodically depressed patients (n=40), and a healthy control group (n=55) using standardized questionnaires. RESULTS: Regardless of the disorder's chronicity, depressed patients exhibited higher levels of autistic traits and lower levels of perspective-taking than healthy controls. Chronically depressed patients reported significantly higher impairment in social skills and higher levels of personal distress in social interactions than episodic patients. DISCUSSION: Our results suggest that patients with chronic depression share two distinct characteristics, namely lower levels of social skills and higher levels of distress in tense social situations than patients with episodic depression. Future studies will need to determine whether the elevated autistic traits in chronic depression are specific to chronic depression, or represent the general tendency to withdraw from social situations. We conclude that chronically depressed patients are not specifically impaired in understanding another person's state of mind, but are unable to deal with another person's suffering or negative affective state. PMID- 26895093 TI - Adaptation of the inflammatory immune response across pregnancy and postpartum in Black and White women. AB - Pregnancy is a period of considerable physiological adaption in neuroendocrine, cardiovascular, as well as immune function. Understanding of typical changes in inflammatory immune responses during healthy pregnancy is incomplete. In addition, despite considerable racial difference in adverse pregnancy outcomes, data are lacking on potential racial differences in such adaptation. This repeated measures prospective cohort study included 37 Black and 39 White women who provided blood samples during early, mid-, and late pregnancy and 8-10 weeks postpartum. Peripheral blood mononuclear cells were incubated with lipopolysaccharide (LPS) for 24h and supernatants assayed by electrochemiluminescence to quantify interleukin(IL)-6, tumor necrosis factor(TNF)-alpha, IL-1beta, and IL-8 production. While no changes were observed in IL-8 production over time, significant increases in IL-6, TNF-alpha, and IL 1beta production were observed from early to late pregnancy, with subsequent declines approaching early pregnancy values at postpartum (ps<0.05). Overall, inflammatory response patterns were highly similar among Black versus White women. However, Black women had greater TNF-alpha production during mid-pregnancy (p=0.002) and marginally lower IL-1beta production at postpartum (p=0.054). These data show a clear trajectory of change in the inflammatory immune response across pregnancy and postpartum. In this cohort of generally healthy women, Black and White women exhibited minimal differences in LPS-stimulated cytokine production across the perinatal period. Future prospective studies in Black and White women with healthy versus adverse outcomes (e.g., preeclampsia, preterm birth) would inform our understanding of the potential role of immune dysregulation in pregnant women and in relation to racial disparities in perinatal health. PMID- 26895094 TI - Polyphenols Variation in Fruits of the Susceptible Strawberry Cultivar Alba during Ripening and upon Fungal Pathogen Interaction and Possible Involvement in Unripe Fruit Tolerance. AB - Strawberry (Fragaria * ananassa) fruit contains high concentrations of health promoting phenolic compounds, playing important roles for the fruit ontogenic tolerance to fungi. In the highly susceptible cultivar Alba, the two major strawberry fungal pathogens, Colletotrichum acutatum and Botrytis cinerea, displayed disease symptoms only at red ripe stages because immature fruits are tolerant to diseases. We analyzed and compared the variation of 47 polyphenols in the surface of unripe and ripe Alba fruits upon 24 and 48 h of C. acutatum and B. cinerea infection or mock inoculation. Significant alteration in phenolic content was detected only in white infected fruit, with differences specific for each pathogen. The expression analysis of phenylpropanoid, flavonoid, and shikimate pathway genes showed in only a few cases correlation with the relative metabolite abundance. The alteration in phenolic content and the lack of consistency with gene expression data are discussed in light of previously reported metabolome data of different susceptible and resistant strawberry genotypes. PMID- 26895096 TI - The Role of the Myocardial Microvasculature in Mental Stress-Induced Myocardial Ischemia. AB - There is increasing evidence that mental stress can manifest as physical diseases. One such condition is mental stress-induced myocardial ischemia (MSIMI); a silent, transient, myocardial ischemic response to stressful conditions. We propose that the cardiac microvasculature may be an important site for the interplay between mental stress and MSIMI. This study is a review of the literature discussing the prevalence and emerging mechanisms underlying MSIMI. We identified several aspects underlying MSIMI, including psychological, genetic, and physiological causes. Several sources suggested that dysfunctional cardiac microvasculature might be a contributing factor in the development of stress induced myocardial ischemia. The literature also suggested that although MSIMI has distinct features and pathophysiology, its occurrence might indicate an increased future risk of cardiovascular events. We found that dysfunctional cardiac microvasculature may be the key point of interaction between mental stress and transient myocardial ischemia and that the development of MSIMI might be a "silent" indicator for future cardiac events. PMID- 26895095 TI - Optical Clearing Delivers Ultrasensitive Hyperspectral Dark-Field Imaging for Single-Cell Evaluation. AB - A single-cell optical clearing methodology is developed and demonstrated in hyperspectral dark-field microscopy (HSDFM) and imaging of plasmonic nanoprobes. Our strategy relies on a combination of delipidation and refractive index (RI) matching with highly biocompatible and affordable agents. Before applying the RI matching solution, the delipidation step by using a mild solvent effectively eliminates those high-density, lipid-enriched granular structures which emit strong scattering. Upon treatment, the background scattering from cellular organelles could be repressed to a negligible level while the scattering signals from plasmonic nanomaterials increase, leading to a significant improvement of the signal-to-noise ratio (SNR). With this method established, the versatility and applicability of HSDFM are greatly enhanced. In our demonstration, quantitative mapping of the dimerization-activated receptor kinase HER2 is achieved in a single cancer cell by a nonfluorescent approach. High-resolution imaging for oncogenic mRNAs, namely ER, PR, and HER2, is performed with single labeling. More importantly, in situ multiplex detection of mRNA and protein is made possible by HSDFM since it overcomes the difficulties of complex staining and signal imbalance suffered by the conventional optical imaging. Last, we show that with optical clearing, characterization of intracellularly grown gold particulates is accomplished at an unprecedented spatiotemporal resolution. Taken together, the uniqueness of optical clearing and HSDFM is expected to open ample avenues for single-cell studies and biomedical engineering. PMID- 26895097 TI - Targeted therapy in esophageal cancer. AB - An increasing number of patients are diagnosed with esophageal cancer at an advanced stages, and only a small group of them can benefit from the traditional chemotherapy and radiotherapy. So far, multiple monoclonal antibodies and tyrosine kinase inhibitors have been developed, alone or in combination with traditional therapy, to improve the prognosis of patients with advanced esophageal cancer. This review summarizes the recent advances of targeted therapies against EGFR, HER2, VEGFR and c-MET in esophageal cancer. More clinical trials should be performed to evaluate the efficacy and safety of various targeted therapy regimens. Future basic research should focus on investigating the molecular mechanisms of therapeutic targets in esophageal cancer. PMID- 26895098 TI - Insomnia, parasomnia, and predisposing factors in Turkish school children. PMID- 26895099 TI - AB209630, a long non-coding RNA decreased expression in hypopharyngeal squamous cell carcinoma, influences proliferation, invasion, metastasis, and survival. AB - Long noncoding RNAs (lncRNAs) are associated with the development, progression, and prognosis of human cancers. However, the clinical significance and biological function of lncRNAs in hypopharyngeal squamous cell carcinoma (HSCC) remain largely unknown. We characterized the novel lncRNA AB209630 in vivo and in vitro. First, using qRT-PCR, we evaluated whether AB209630 levels differ between HSCC tissues/cell lines and adjacent normal tissues/cell lines. We then assessed whether AB209630 expression levels stimulate or inhibit proliferation, invasion, apoptosis, and metastasis in vitro. Finally, we investigated whether AB209630 levels in tumor tissues were associated with survival outcomes. Our results demonstrated that AB209630 levels were markedly lower in HSCC tissues and cells than in normal tissues and cells, and increased expression of AB209630 level significantly inhibited growth, metastasis, and invasion and stimulated apoptosis in vitro. In addition, patients with decreased expression of AB209630 had a significantly poorer prognosis than those with high AB209630 expression. These data suggest that increased expression of AB209630 might either stimulate or inhibit biological activities involved in HSCC development, indicating a potential application of AB209630 in future treatment for this disease. This study suggest that AB209630 functions as a tumor suppressor in HSCC, and its decreased expression may help predict a poor prognostic outcome of HSCC. Our future work will focus on the mechanisms of whether and how AB209630 as a tumor suppressor gene is involved in HSCC development. PMID- 26895100 TI - MPC1, a key gene in cancer metabolism, is regulated by COUPTFII in human prostate cancer. AB - Mitochondrial pyruvate carrier 1 (MPC1) and MPC 2 form a transporter complex in cells to control pyruvate transportation into mitochondria. Reduced expression of MPC1 disrupts the transporter function, induces metabolic shift to increase glycolysis, and thus plays important roles in several diseases, including cancer. However, the role of MPC1 in prostate cancer and the underlying mechanism causing the down-regulation of MPC1 in tumor cells remain to be defined. Here, we show that MPC1 serves as a critical regulator of glycolysis in prostate cancer cells, which in turn controls cancer cell growth, invasion, and the tumorigenic capability. More importantly, we identified that chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII), a steroid receptor superfamily member, transcriptionally regulates the expression of MPC1. We further demonstrate that COUP-TFII, which is upregulated in the prostate cancer patient, regulates MPC1 and glycolysis to promote tumor growth and metastasis. Our findings reveal that COUP-TFII represses MPC1 expression in prostate cancer cells to facilitate a metabolism switch to increase glycolysis and promote cancer progression. This observation raises an intriguing possibility of targeting COUP TFII to modulate cancer cell metabolism for prostate cancer intervention. PMID- 26895101 TI - Use of integrin alpha 6 transcripts in a stool mRNA assay for the detection of colorectal cancers at curable stages. AB - OBJECTIVE: An important criterion for colorectal cancer (CRC) screening is the ability to detect lesions at a curable stage. In the present study, we have assessed the integrin alpha6 subunit transcript (ITGA6) as part of a stool assay for the detection of colorectal lesions. RESULTS: In comparison with control samples, ITGA6 levels were found to be significantly increased at all stages (P < 0.01). Receiver operating characteristic analysis revealed areas under the curve of 0.89 for the prediction of CRC with 81% sensitivity and 88% specificity and of 0.90 for the prediction of advanced adenomas (Ad) with 75% sensitivity and 88% specificity. The ITGA6A variant was also found to be increased relative to ITGA6 in stage II and III CRCs. Combining ITGA6 with other selected transcripts and/or immunochemical fecal occult blood test (iFOBT) results further increased sensitivity and specificity for the detection of colorectal lesions. PATIENTS AND METHODS: ITGA6 detection used alone and under various combinations including detection of other mRNA markers and iFOBT was assessed on stool samples obtained from 175 patients (91 CRCs, 24 Ad and 60 healthy controls). CONCLUSIONS: These data confirm the usefulness and reliability of an mRNA stool assay for the detection of colorectal lesions. The validation of additional candidate genes and their analysis in multiplex qPCR represents a powerful and robust approach that can be combined with iFOBT results to improve the detection of colorectal lesions. PMID- 26895102 TI - The cancer-testis antigens SPANX-A/C/D and CTAG2 promote breast cancer invasion. AB - Genes that are normally biased towards expression in the testis are often induced in tumor cells. These gametogenic genes, known as cancer-testis antigens (CTAs), have been extenstively investigated as targets for immunotherapy. However, despite their frequent detection, the degree to which CTAs support neoplastic invasion is poorly understood. Here, we find that the CTA genes SPANX-A/C/D and CTAG2 are coordinately induced in breast cancer cells and regulate distinct features of invasive behavior. Our functional analysis revealed that CTAG2 interacts with Pericentrin at the centrosome and is necessary for directional migration. Conversely, SPANX-A/C/D interacts with Lamin A/C at the inner nuclear membrane and is required for the formation of actin-rich cellular protrusions that reorganize the extracellular matrix. Importantly, SPANX-A/C/D was required for breast cancer cells to spontaneously metastasize to the lung, demonstrating that CTA reactivation can be critical for invasion dependent phenotypes in vivo. Moreover, elevated SPANX-A/C/D expression in breast cancer patient tumors correlated with poor outcome. Together, our results suggest that distinct CTAs promote tumor progression by regulating complementary cellular functions that are integrated together to induce invasive behavior. PMID- 26895103 TI - Expression of GADS enhances FLT3-induced mitogenic signaling. AB - GADS is a member of a family of SH2 and SH3 domain-containing adaptors that functions in tyrosine kinase-mediated signaling cascades. Its expression is largely restricted to hematopoietic tissues and cell lines. Therefore, GADS is mainly involved in leukocyte-specific protein tyrosine kinase signaling. GADS is known to interact with tyrosine-phosphorylated SHC, BCR-ABL and KIT. The SH2 domain of GADS has a similar binding specificity to that of GRB2 but its SH3 domain displays a different binding specificity, and thus it is involved in other downstream signaling pathways than GRB2. In the present study, we examined the role of GADS in FLT3 signaling. FLT3 is a type III receptor tyrosine kinase, which is mutated in more than 30% of acute myeloid leukemia (AML) and the most common mutations is the internal tandem duplication (ITD) mutations. We observed that expression of GADS enhanced oncogenic FLT3-ITD-induced cell proliferation and colony formation in vitro. In a mouse xenograft model, GADS accelerated FLT3 ITD-dependent tumor formation. Furthermore, expression of GADS induced a transcriptional program leading to upregulation of MYC and mTORC1 target genes. GADS localizes to the cell membrane and strongly binds to ligand-stimulated wild type FLT3 or is constitutively associated with the oncogenic mutant FLT3-ITD. We mapped the binding sites in FLT3 to pY955 and pY969 which overlaps with the GRB2 binding sites. Expression of GADS enhanced FLT3-mediated phosphorylation of AKT, ERK1/2, p38 and STAT5. Taken together, our data suggests that GADS is an important downstream component of FLT3 signaling and expression of GADS potentiates FLT3-mediated mitogenic signaling. PMID- 26895104 TI - Quantitative proteomics reveals the novel co-expression signatures in early brain development for prognosis of glioblastoma multiforme. AB - Although several researches have explored the similarity across development and tumorigenesis in cellular behavior and underlying molecular mechanisms, not many have investigated the developmental characteristics at proteomic level and further extended to cancer clinical outcome. In this study, we used iTRAQ to quantify the protein expression changes during macaque rhesus brain development from fetuses at gestation 70 days to after born 5 years. Then, we performed weighted gene co-expression network analysis (WGCNA) on protein expression data of brain development to identify co-expressed modules that highly expressed on distinct development stages, including early stage, middle stage and late stage. Moreover, we used the univariate cox regression model to evaluate the prognostic potentials of these genes in two independent glioblastoma multiforme (GBM) datasets. The results showed that the modules highly expressed on early stage contained more reproducible prognostic genes, including ILF2, CCT7, CCT4, RPL10A, MSN, PRPS1, TFRC and APEX1. These genes were not only associated with clinical outcome, but also tended to influence chemoresponse. These signatures identified from embryonic brain development might contribute to precise prediction of GBM prognosis and identification of novel drug targets in GBM therapies. Thus, the development could become a viable reference model for researching cancers, including identifying novel prognostic markers and promoting new therapies. PMID- 26895105 TI - miR-486-5p expression pattern in esophageal squamous cell carcinoma, gastric cancer and its prognostic value. AB - Micro RNA (miR)-486-5p is often aberrantly expressed in human cancers. The aim of this study was to identify the prognostic value of miR-486-5p expression in digestive system cancers. Tissue microarrays were constructed with 680 samples including 185 esophageal squamous cell carcinomas (ESCCs), 90 gastric adenocarcinomas (GCs), and 60 digestive system cancer tissues from 10 ESCC, 10 GC, 10 colon, 10 rectum, 10 liver, 10 pancreatic cancer, and corresponding normal tissues. Twenty normal digestive system mucosa tissues from healthy volunteers were included as normal controls. In GC, miR-486-5p expression was decreased in 62.8% of cases (59/94), increased in 33.0% (31/94), and unchanged in 4.2% (4/94); in ESCC its expression was decreased in 66.2% (129/195), increased in 32.3% (63/195), and unchanged in 1.5% (3/195). Expression of miR-486-5p was decreased in 12, and increased in 8, of 20 cases of colon or rectum cancer; decreased in 6, and increased in 4, of 10 cases of liver cancer; and decreased in 8, and increased in 2, of 10 cases of pancreatic cancer. Multivariate and univariate regression analysis demonstrated that low/unchanged miR-486-5p predicted poor prognosis in ESCC (hazard ratio [HR], 4.32; 95% confidence interval [CI], 2.62 7.14; P < 0.001; HR, 3.88; 95% CI, 2.43-6.22; P < 0.001, respectively) and GC (HR, 2.46; 95% CI, 1.35-4.50; P = 0.003; HR, 2.55; 95% CI, 1.39-4.69; P = 0.002, respectively). MiR-486-5p might therefore be an independent tumor marker for evaluating prognosis in patients with ESCC or GC. PMID- 26895106 TI - Pathway of PPAR-gamma coactivators in thermogenesis: a pivotal traditional Chinese medicine-associated target for individualized treatment of rheumatoid arthritis. AB - Traditional Chinese medicine (TCM) syndromes have been regarded as the crucial clinical manifestations for individualized diagnosis and treatment of complex diseases, including rheumatoid arthritis (RA) and cancer. Especially, RA patients are classified into cold and hot syndromes with different clinical manifestations, interventions and molecular mechanisms. Better effectiveness of a classic cold syndrome-specific herbal formula Wu-tou decoction (WTD) has been achieved. To explore molecular mechanisms of syndrome-specific formulae is of great clinical significance to improve the effectiveness and pertinence of treatment for the complex diseases with personalized conditions. However, the scientific basis of WTD treatment on RA with the cold syndrome remains unclear. Here, we predicted the putative targets for composite compounds contained in WTD using drugCIPHER-CS and constructed a WTD herbs-putative targets-RA related genes network. Next, a list of major WTD targets was identified based on their topological features, including the degree, node betweenness, closeness and k coreness in the above pharmacological network. Importantly, pathway enrichment analysis revealed that these major WTD targets were significantly associated with the pathway of peroxisome proliferator-activated receptor (PPAR)-gamma (PPAR gamma) coactivators in thermogenesis. These computational findings were subsequently verified by experiments on a rat model of collagen-induced arthritis (CIA) with cold or hot syndromes, and on human fibroblast-like synoviocytes rheumatoid arthritis (HFLS-RA) cell line. In conclusion, the pathway of PPAR gamma coactivators in thermogenesis might be one of the potential pharmacological targets of WTD to alleviate RA with the TCM cold syndrome. These findings may open new avenues for designing individualized treatment regimens for RA patients. PMID- 26895107 TI - The significance of phosphorylated heat shock protein 27 on the prognosis of pancreatic cancer. AB - BACKGROUND AND AIM: The precise role of phosphorylated heat shock protein (HSP) 27 (p-HSP27) in pancreatic cancer remains to be elucidated. The aim of this study was to investigate whether the expression of p-HSP27 predicts the prognosis of patients with pancreatic cancer. METHODS: We retrospectively assessed 49 biopsied pancreatic cancer tissue samples that were obtained prior to the treatment with gemcitabine. The correlations between p-HSP27 and the clinicopathological characteristics were analyzed. RESULTS: p-HSP27 was not correlated with the response to chemotherapy or histological type. However, the median survival time was significantly longer in the patients with high p-HSP27 (275 days, n = 18) than those with low p-HSP27 (205 days, n = 31) (P = 0.0158). A multivariate Cox proportional hazards regression analysis revealed that low p-HSP27 predicted a worse prognosis. CONCLUSIONS: Higher p-HSP27 expression before chemotherapy was correlated with better survival, indicating that p-HSP27 expression could be used to predict the prognosis of pancreatic cancer. PMID- 26895109 TI - CXCL10 and blood-brain barrier modulation in rabies virus infection. PMID- 26895110 TI - Role of microRNAs in epigenetic silencing of the CHD5 tumor suppressor gene in neuroblastomas. AB - Neuroblastoma (NB), a tumor of the sympathetic nervous system, is the most common extracranial solid tumor of childhood. We and others have identified distinct patterns of genomic change that underlie diverse clinical behaviors, from spontaneous regression to relentless progression. We first identified CHD5 as a tumor suppressor gene that is frequently deleted in NBs. Mutation of the remaining CHD5 allele is rare in these tumors, yet expression is very low or absent, so expression is likely regulated by epigenetic mechanisms. In order to understand the potential role of miRNA regulation of CHD5 protein expression in NBs, we examined all miRNAs that are predicted to target the 3'-UTR using miRanda, TargetScan and other algorithms. We identified 18 miRNAs that were predicted by 2 or more programs: miR-204, -211, -216b, -17, -19ab, -20ab, -93, 106ab, -130ab, -301ab, -454, -519d, -3666. We then performed transient transfections in two NB cell lines, NLF (MYCN amplified) and SY5Y (MYCN non amplified), with the reporter plasmid and miRNA mimic, as well as appropriate controls. We found seven miRNAs that significantly downregulated CHD5 expression in NB: miR-211, 17, -93, -20b, -106b, -204, and -3666. Interestingly, MYCN upregulates several of the candidates we identified: miR-17, -93, -106b & -20b. This suggests that miRNAs driven by MYCN and other genes represent a potential epigenetic mechanism to regulate CHD5 expression. PMID- 26895112 TI - Descending aortic replacement after Nuss for pectus excavatum in a Marfan patient Case report. AB - INTRODUCTION: The Nuss procedure for pectus excavatum (PE) repair has been successfully performed in Marfan syndrome (MFS) patients however there is concern for future risk of aortic dilation/rupture and need for emergent access with support bars in place. CASE PRESENTATION: We present a 45 year-old male with MFS that required descending aortic replacement shortly after modified Nuss repair. DISCUSSION: The majority of MFS patients have severe PE and repair with the Nuss procedure is not uncommon. The risk for life threatening aortic dilation, dissection, or rupture in such patients is a concern when utilizing this technique. Our work has been reported in line with the CARE criteria. CONCLUSION: Nuss repair should be considered in MFS patients with technique modifications and careful consideration of future risk of aortic dilation and rupture. PMID- 26895113 TI - Gastrointestinal stromal tumor of the vermiform appendix mimicking Meckel's diverticulum: Case report with literature review. AB - INTRODUCTION: Gastrointestinal stromal tumors (GISTs) of the appendix are extremely rare. To date, only 15 cases have been reported in the English literature. Here, we present a new case of an appendiceal GIST with appendicitis. PRESENTATION OF CASE: A 68-year-old man who complained of right lower abdominal tenderness underwent surgery for a cystic mass mimicking Meckel's diverticulum. Laparoscopy revealed a mass protruding from the proximal appendix with distal appendicitis. Complete resection with adequate margins was performed. Histology showed a spindle cell GIST without mitotic activity as well as a strong expression of CD117 and CD34. CONCLUSION: Primary appendiceal GIST occur at a very low rate and their symptoms are nonspecific. Accordingly, rare tumors of appendix including GISTs should be considered in the differential diagnosis of atypical symptoms or image findings. PMID- 26895111 TI - pH-Activatable MnO-Based Fluorescence and Magnetic Resonance Bimodal Nanoprobe for Cancer Imaging. AB - Stimuli-responsive nanoprobes that combine both fluorescence and magnetic resonance imaging (MRI) are anticipated to be highly beneficial for tumor visualization with high imaging sensitivity. By employing an interfacial templating scheme, a pH-activatable fluorescence/MRI dual-modality imaging nanoprobe is successfully developed based on the coencapsulation of MnO nanoparticles and coumarin-545T inside a hybrid silica nanoshell. To promote cancer cell targeting with high-specificity, the nanoprobes are also conjugated with folic acid to establish a greater affinity for cancer cells that over express folate receptors on their cell membrane. In the new nanosystem, MnO nanoparticles are shown to function as an efficient fluorescence quencher of coumarin-545T prior to cellular uptake. However, fluorescence recovery is achieved upon acidic dissolution of the MnO nanoparticles following receptor mediated endocytosis into the low pH compartments of the cancer cells. Meanwhile, the Mn(2+) ions thus released are also shown to exert a strong T1 contrast enhancement in the cancer cells. Therefore, by demonstrating the dual-activatable MRI and fluorescence imaging in response to the low pH conditions, it is envisioned that these nanoprobes would have tremendous potential for emerging cancer-imaging modalities such as image-guided cancer therapy. PMID- 26895108 TI - HMGA1-pseudogenes and cancer. AB - Pseudogenes are DNA sequences with high homology to the corresponding functional gene, but, because of the accumulation of various mutations, they have lost their initial functions to code for proteins. Consequently, pseudogenes have been considered until few years ago dysfunctional relatives of the corresponding ancestral genes, and then useless in the course of genome evolution. However, several studies have recently established that pseudogenes are owners of key biological functions. Indeed, some pseudogenes control the expression of functional genes by competitively binding to the miRNAs, some of them generate small interference RNAs to negatively modulate the expression of functional genes, and some of them even encode functional mutated proteins. Here, we concentrate our attention on the pseudogenes of the HMGA1 gene, that codes for the HMGA1a and HMGA1b proteins having a critical role in development and cancer progression. In this review, we analyze the family of HMGA1 pseudogenes through three aspects: classification, characterization, and their possible function and involvement in cancer. PMID- 26895114 TI - Does situs inversus totalis preclude liver donation in living donor liver transplantation? A series of 3 cases from single institution. AB - INTRODUCTION: Liver transplantation (LT) is the gold standard for decompensated Chronic Liver Disease (CLD) in individuals satisfying the selection criteria. Organ scarcity is the rate limiting step in liver transplantation across the globe. Expanding the donor pool is practiced by transplant surgeons across the globe in view of perennial donor organ scarcity and ever increasing organ demand. PRESENTATION OF CASE: We have presented series of 3 cases of liver transplantation (LT) with modified left lobe (conventional right) graft from a situs inversus donor and implanting it as a conventional right lobe with a modified technique. The grafts had Type 1, Type 2 and Type 3 biliary anatomies. One graft had inferior hepatic veins also. All three patients had uneventful recoveries. The follow up period range is 4 years to 8 months. DISCUSSION: There are multiple case reports in the literature involving situs inversus donors in liver transplantation. Various techniques have also been described. We describe simple and effective technique which has proved successful to our patients. CONCLUSION: SIT donors can be safely accepted for living donor liver transplantation. It is a technically challenging procedure both for donor liver harvesting and implantation in recipient. This is the first case series of LT using modified left lobe graft (conventional right) from a SIT donor with 2 different techniques. Biliary anastomosis is the tricky part of the operation. PMID- 26895116 TI - Perovskite Photovoltaics with Outstanding Performance Produced by Chemical Conversion of Bilayer Mesostructured Lead Halide/TiO2 Films. AB - A new method of producing high-quality perovskite films via sequential deposition is presented, introducing a PbX2 capping layer that is endowed with a network of interconnected nanopores. The mesoporous lead halide architecture provides a powerful tool to accomplish rapid and complete transformation of lead halide into the perovskite for high-efficiency solar cells. PMID- 26895115 TI - Expanding HIV Testing in African American Communities Through Community-Based Distribution of Home-Test Vouchers. AB - We investigated the implementation feasibility and effectiveness of community based HIV home-test voucher distribution in three Indianapolis African American communities. Community-based organizations augmented traditional outreach methods to distribute vouchers for home HIV tests redeemable at three pharmacies during three distribution waves from February to April 30, 2015. Voucher redemption served as a proxy indicator of intent to test for HIV. 315 vouchers were distributed and 47 vouchers were redeemed for a 14.9% redemption rate. Distribution was 46% of plan. Vouchers were redeemed at all three pharmacies, and 21% of visits involved redemption of more than one voucher. The original team of seven distributors in three organizations reduced to a remaining five distributors in two organizations by wave 2. This study suggests that outreach organizations could implement HIV home test voucher distribution, and that people would redeem the vouchers at a pharmacy for an HIV test. Future studies should explore how voucher distribution can expand the current HIV testing system. PMID- 26895117 TI - "Gastric bypass" or "sleeve gastrectomy" for morbid obesity : a systematic review. AB - BACKGROUND: Bariatric surgery represents an efficient treatment of morbid obesity allowing not only weight loss but also the control of comorbidities related to obesity. Although the sleeve gastrectomy and gastric bypass are currently the two most common procedures, the superiority of one over another and the indications remain imprecise. AIM: The aim of this work was to provide an evidence based answer to the following questions: What is the most efficient surgical procedure: gastric bypass or sleeve gastrectomy regarding weight loss, postoperative morbidity and remission of comorbidities related to obesity? METHODS: A literature search has been conducted in the data bases of Pubmed, Cochrane Library and Scopus during the period between January 2008 to March 2015, with the keywords "Gastric Bypass" and "Sleeve Gastrectomy". RESULTS: the results of sleeve gastrectomy and gastric bypass regarding weight loss and remission of comorbidities are comparable in the short and medium terms. Gastric Bypass is associated with a longer duration of surgery, a slightly higher early morbidity and more frequent deficiencies in vitamins D and B12 but it allows a better control of a pre-operative gastroesophageal reflux disease. CONCLUSION: Sleeve gastrectomy and gastric bypass are equivalent in terms of loss of weight and control of comorbidities but longer term studies are needed to refine the indications depending on the characteristics of the patient. PMID- 26895118 TI - Drug Rash with Eosinophilia and Systemic Symptoms to antituberculosis treatment. AB - Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome reflects a serious hypersensitivity reaction to drugs. This syndrome is an uncommon adverse reaction due to antituberculosis drugs and is sometimes difficult to identify the culprit agent. We report a case of a 45-year-old woman who received combined antituberculosis drugs (RHZE) for lymph node tuberculosis. Clinical manifestations included fever, dyspnea, rash, hypereosinophilia and visceral involvement (liver involvment). After symptom resolution and biology normalization, anti-tuberculosis drugs were reintroduced successively one after another. Systemic symptoms reappeared with the four anti-tuberculosis drugs. The clinical outcome was favorable with second line antituberculosis treatment. PMID- 26895119 TI - Laparoscopic resection of gastric stromal tumors. AB - Gastro-intestinal stromal tumors (GIST) are the most common mesenchymal gastrointestinal tumors. The Gastric location represents 60% of cases [1,2]. Complete surgical excision remains the treatment of reference for the localized forms. This surgery can be made by laparoscopy when the lesion's size doesn't exceed 5 cm. Some principles must e respected: a mono-block complete surgical resection, with healthy margins and without effraction. This technique will be reserved for trained teams and for selected cases according to the size and location. We herein try to explain the surgical laparoscopic excision of gastric stromal tumors explaining . PMID- 26895120 TI - Glioblastoma in Tunisia: A retrospective study about 41 cases. AB - BACKGROUND: Glioblastoma (GB) is the most common and lethal primary brain tumor in adults representing 25% of primary brain tumors in adults. The objective of our study was to report the epidemiologic, clinical and therapeutic features of GB in Tunisia. METHODS: Our retrospective study included 41 patients with histologically confirmed GB treated between 2006 and 2012 at the medical oncology departments of Abderrahmane Mami hospital in Ariana and the military hospital in Tunis. RESULTS: Median age was 54 years (13 to 72 years) and sex-ratio was 2.3. Karnofsky performance status (KPS) was <70% in 31.7% of cases, while Recursive partitioning analysis radiation therapy oncology group (RTOG-RPA) classification was III in 11 (26.8%), IV in 19 (46.3%), V in 10 (24.3%) and VI in 1 (2.4%) cases. Complete resection (CR) was achieved in 29 patients (70.7%), partial resection (PR) or tumor debulking in 5 patients (12.2%) and biopsy alone (BA) in 7 patients (17.1%). All patients received brain radiotherapy (RT) at a dose of 60 Gy combined with concurrent temozolomide (TMZ). Nineteen patients (46.3%) received adjuvant TMZ, 8 of them completed 6 cycles. Median overall survival (OS) was 12 months (2 to 56 months). Six, 12, 18 and 24-months OS rates were 84.6%, 57.6%, 35.4% and 20.7%, OS being correlated to age, KPS, RPA and quality of resection. CONCLUSION: Our retrospective study is the first African GB series. Despite it included predominantly poor prognosis patients with impaired neurocognitive function and adjuvant treatment discontinuation, our median OS was comparable to Stupp. PMID- 26895121 TI - Microbiological study and antimicrobial susceptibility of bile in biliary therapeutic endoscopy. AB - BACKGROUND: Biliary obstruction together with bacterial colonization of the bile duct may lead to development of acute cholangitis. The reported incidence of infectious complications may reach up to 10%. Nevertheless, no antibiotic prophylaxis is administered routinely, prior to endoscopic therapeutic procedures. AIM: To investigate the presence and degree of biliary bacterial colonization during endoscopic retrograde cholangiopancreatography (ERCP) in patients with biliary obstruction. Furthermore, we evaluated antibiotic therapy regimens, which would cover the bacterial species obtained by ERCP and subsequent culture in each patient. METHODS: Forty-four patients with biliary obstruction who underwent an ERCP with biliary drainage were prospectively included. The primary indication of ERCP was choledocholithiasis (48%), followed by benign biliary strictures (32%) and malignant bile duct obstruction (18%). Bile cultures were obtained by means of bile aspiration via the cannulation catheter. Aerobic and anaerobic cultures were prepared from all obtained specimens and the isolated organisms were identified. In the case of positive cultures, an in-vitro resistance test for different antibiotics was performed. RESULTS: The overall positive rate of bile culture was 93%. The organisms cultured were Escherichia coli (26.8%), Enterococcus (17%), Klebsiella (14.6%), Enterobacter (14.6%) and Pseudomonas (9.7%) in decreasing order. In-vitro testing of different antibiotics was carried out in these 41 isolates. Imipenem showed the best antimicrobial activity (sensitivity, 100%), followed by colistin (94%), tobramycin (93%), amikacin (89.6%), gentamycin (85.2%) and ceftazidin (82%). Amoxicillin/clavulanic acid and ofloxacin were less sensitive (66% and 60% respectively). Ceftazidin was the most effective antibiotic on Escherichia coli (sensitivity 83%). Multi resistant organisms were noted in 22% of the cases. CONCLUSIONS: Escherichia coli was found to be the pathogen most frequently detected in bile following endoscopic interventions in the biliary tract. Enterococci and Klebsiella were found in bile cultures with an incidence exceeding 10%. In view of the in-vitro test results, amoxicillin/clavulanic acid or quinolons are not suitable antibiotics for the prophylaxis of biliary infections. Moreover, Gram-positive bacteria such as Enterococcus are emerging as causative microorganisms. If these organisms are isolated, antimicrobial drugs should be replaced by narrower spectrum antimicrobials. PMID- 26895122 TI - Argon plasma coagulation in the management of symptomatic gastrointestinal angiodysplasia: experience in 69 consecutive patients. AB - BACKGROUND: Gastrointestinal angiodysplasias are associated with a high bleeding risk. AIM: to evaluate the efficiency of argon plasma electrocoagulation in the treatment of gastrointestinal angiodysplasia and to identify predictive factors of success of this technique. METHODS: Retrospective study of patients with bleeding gastrointestinal angiodysplasia treated with argon plasma electrocoagulation in the digestive endoscopy unit of the military hospital in Tunis between January 2000 and December 2011. RESULTS: 69 patients with a mean age of 68.7 years were included.The endoscopic treatment resulted in a rise in hemoglobin value from 7.3 to 9.3 g/ dl (p = 0.0001) and a decrease of transfusion requirements from 2.5 to 0.1 units of packed red cells (p <0.0001). It allowed to avoid surgery for 93.6% of patients with complex medicalhistory. Recurrence of bleeding was observed in 33.3% of patients after a mean time of 12.3 months. In a multivariate analysis, no factors were independently associated with the recurrence of bleeding. The overall survival without rebleeding at 1 and 2 years were 50% and 42% respectively. CONCLUSION: Argon plasma coagulation is an easy, effective and safe treatment of bleeding angiodysplasia. This technique is particularly interesting for patients with multiple medical problems, where surgical treatment could be burdened by significant morbidity and mortality risk. PMID- 26895123 TI - Short, midterm and late results of percutaneous coronary interventions for left main coronary artery disease. AB - BACKGROUND: Left main coronary artery disease is found in 4-6% of patients undergoing diagnostic coronary angiography. Coronary artery bypass graft is the gold standard. However, percutaneous coronary intervention is a continuously evolving substitution for surgery in such patients. METHODS: We report a retrospective study of 32 patients with relevant left main coronary artery disease treated by angioplasty in our faculty, between January 2005 and March 2011. RESULTS: The mean age of the population on the study was 59.7+/-10.9 years. The sex-ratio was 3.57. The rate of angiographic success was 97%. The in-hospital stay was uneventful in 94%of our patients. Only one patient died of cardiogenic shock complicating an acute anterior myocardial infarction. After a mean follow up of 18.5 +/- 15.4 months, the in-stent restenosis rate was 16.12%. The rate of major adverse cardiac events (MACE) was 29%. Independent predictive factors of MACE were: cardiogenic shock on admission (p=0.022), emergency procedures (p=0.033), Euroscore > 6 (p=0.001), Parsonnet score > 20 (p=0.036), High C reactive protein levels on admission (p=0.007),le taux de creatinine (p=0.008), un diametre de reference du TCCG < 3.5 mm (p =0.036) et l'utilisation de stents (p=0.036) and the use of bare metal stents (p=0.036). Independent predictive factors of in-stent restenosis were: use of bare metal stents (p=0.004) and Paclitaxel drug eluting stents (p=0.037). CONCLUSION: Percutaneous coronary intervention is safe and a validated alternative to coronary artery bypass graft for left main coronary artery disease. However, it should be reserved to selected patients and limited to experienced centers. PMID- 26895124 TI - Epidemiology of open globe injuries in cap bon: about 100 cases. AB - BACKGROUND: Open globe injuries are a major cause of permanent visual impairment and blindness. OBJECTIVES: In this retrospective study, we identify clinical characteristics and outcome of a series of open globe injuries. METHODS: Operating department records were reviewed to identify all patients who had undergone repair of an open globe injury from January 2006 to November 2013 at the department of ophtalmology in the university hospital of Nabeul in Tunisia. Case notes were examined to determine demographic data, mechanisms and location of injury. The Snellen visual acuity on presentation, initial clinical signs and the final visual acuity were, also, recorded. RESULTS: In total, 100 cases of open globe injury were identified. The mean age of the patients was 31.9 years. Eighty-two per cent (82%) of patients were male. Domestic accidents, assaults and accidents in the work place were the main etiologies of open globe injuries, representing respectively 30, 29 and 12% of cases. Twenty eight (28) patients had globe ruptures and 72 patients sustained globe lacerations. The injury was corneal in 60 cases, corneoscleral in 15 cases and scleral in 25 cases. An intraocular foreign body has been identified in 4 cases. The main complications were corneal opacity (43%) and posterior synechiae (28.6%). Final visual acuity of 5/10 or better was achieved in 24% of cases. It was <=1/10 in 12 % of cases. CONCLUSION: Open globe injury is a serious accident that can cause significant functional impairment. Only the application of preventive measures can reduce the incidence of these accidents. PMID- 26895125 TI - Quality of life of working women: results of a Tunisian study using the 36 item short from health survery questionnaire (sF-3-6). AB - BACKGROUND: The need for a scientific evaluation of the work life quality has become today evident to all. AIM: This study aims to evaluate the short-term impact of the workload on the quality of life of employed Tunisian women. METHODS: A cross-sectional survey on a representative sample of 394 women working in the sectors of textile, shoe-manufacturing and administration was conducted between 2009 and 2010. The quality of life was assessed using the 36-item Short Form Health Survey questionnaire (SF-36). RESULTS: The overall quality of life score was 67.2 +/- 15.2. There was an uneven weathering of the different SF-36 scales. Vitality scale was the most affected with a score below 50. Quality of life of employed women differed significantly depending on the activity sector (p<= 0.001). The SF-36 score value was lower in the sector of textile. Social load, physical and mental workload significantly influenced the quality of life. CONCLUSION: The quality of life in employed women was correlated with the workload. The use of SF-36 to measure the quality of life is useful for the evaluation of work life quality. PMID- 26895126 TI - Monocentric study of Willebrand's disease in Tunisia: assets and difficulties. AB - BACKGROUND: Von Willebrand's disease (VWD) is the most commonly inherited bleeding disorder. It is characterized by clinical, biological and molecular heterogeneity. In certain types of the disease, diagnosis can be difficult. AIM: We report the clinico-biological characteristics of VWD's patients and analyze diagnosis difficulties. METHODS: 33 cases were diagnosed in the laboratoryfrom February to May, 2011. Screening hemostasis included the measuring of FVIII: C, VWF: Ag and VWF: RCo. Blood cell count and blood group were performed in all cases. RESULTS: Mean age at diagnosis is 13 years [10 months -43 years]. The sex ratio M/F is 0.5. The patients are classified type 3 VWD in 52% of the cases, type 2 VWD in 30 % of the cases and type 1 VWD in 18 % of the cases. The diagnosis of type 2B VWD suspected in combination of the ratio VWF:RCo / VWF: Ag <0,7 and thrombocytopenia in one case. Required tests for positive diagnosis and distinction between the primary categories of VWD are available. Specialized tests will allow a best characterization variants type 2 VWD for a better therapeutic approach. PMID- 26895127 TI - The general practitioner facing acute infant bronchiolitis: multicenter study in Tunis. AB - BACKGROUND: The acute bronchiolitis in infants (ABI) constitutes a health problem, responsible for a congestion of the care system, particularly emergencies. OBJECTIVES: This study aims to assess the knowledge, attitudes, and the frontline general practitioners' behavior, and describe the availability of the base pediatric equipment in health centers, in Tunis. METHODS: Cross sectional descriptive survey was conducted in 2013 at 50 health centers in the region with physicians, conducted by selfadministered anonymous questionnaire and a data sheet detailing the equipment at the health center. Seizure and data analysis is made by Epi Info 6. RESULTS: The responder doctors have over 20 years of seniority for 64% of them and have all received training in ABI. In knowledge 75 to 80% master the definition of the ABI and the main criteria of severity, but only 35% identified less than 3 months of age as a risk factor and less than half provide prevention tips. Regarding the physicians behavior, chest X-ray and kinesitherapy continues to be prescribed in respectively 23 and 37% of cases, the same applies for corticoid (25%). Nasopharyngeal desobstruction is only recommended in 60% of cases. In regard to the health centers equipment, they were judged satisfactory overall, except for the absence of oxygen sources in 66% of them. CONCLUSION: Acute Bronchiolitis in infants remains over-medicated at the level of frontline medical consultation in Tunis. It is necessary to revise the terms of skills updating of the general practitioners in care and prevention, conduct and disseminate easy and attractive communication tools (brochures and posters) and implement seasonal data collection of this disease in sentinel sites. PMID- 26895128 TI - Risk of mortality due to device associated infection. AB - BACKGROUND: Intensive care unit -acquired infections constitute an important worldwide health problem. AIM: Our aim was to determine the incidence and risk factors of device-associated infection and those of mortality in a Tunisia ICU. METHODS: We conducted a prospective observational cohort study over a six months period in the adult medical intensive care unit of University Hospital-Farhat Hached (Sousse-Tunisia). Patients admitted to the unit were included in the study if they stayed in the ICU for more than 48 hours. RESULTS: During the study period, 105 patients were surveyed; 16 of them (15.2%) developed 17 episodes of device associated infections (16.9 DAI/1000 days of hospitalization). The most frequently identified infections were central and peripheral venous catheter associated infection (respectively, 21.4 CVC-AI/ 1000 CVC-days and 10.2 PVCAI / 1000 PVC-days). At ICU discharge, overall mortality was 40%. Independent risk factors for acquiring infection in ICU were the use of central venous catheter (p=0.031) and length stay (0.002), those of mortality in ICU were immunosuppression (p=0.013), DAI (p=0.002) and the use of central venous catheter (p = 0.001). CONCLUSION: Even if DAI rates in Tunisian ICU were lower than those published in some reports from other North African countries, DAI data and mortality rate, dominated by the use of catheter associated infections show the need for more-effective infection control interventions in our hospital. PMID- 26895129 TI - Predictive score for positive upper endoscopies outcomes in children with upper gastrointestinal bleeding. AB - BACKGROUND: Upper gastrointestinal bleeding (UGIB) is a common pediatric emergency. Esophago-gastro-duodenoscopy (EGD) is the first line diagnostic procedure to identify the source of bleeding. However etiology of UGIB remains unknown in 20% of cases. Furthermore, emergency endoscopy is unavailable in many hospitals in our country. AIMS: Identify clinical predictors of positive upper endoscopy outcomes and develop a clinical prediction rule from these parameters. METHODS: Retrospective study of EGDs performed in children with first episode of UGIB, in the endoscopic unit of Children's Hospital of Tunis, during a period of six years. Statistical analysis used SPSS20. Univariate analysis was performed and multivariate logistic regression was then modelled to derive a clinical prediction rule. RESULTS: We collected 655 endoscopies (23.2% normal, 76.8% pathological). We found that time to EGD within 24 hours from the onset of bleeding (p=0.027; Adj OR: 3.30 [1.14 - 9.53]), rebleeding (p=0.009; Adj OR: 6.01 [1.57 - 23.02]), positive gastric lavage outcome (p=0.001; Adj OR: 4.79 [1.95 - 11.79]) and non steroidal anti-inflammatory drugs intake (p=0.035; Adj OR: 5.66 [1.13 - 28.31]) were predictors of positive upper endoscopy outcomes. By assigning each factor, the adjusted odds ratio (Adj OR), we developed a score with four items, ranging from 4 to 20. Using the receiver operating characteristic (ROC) curve the best cut off >= 9 was defined (sensitivity 88.2%, specificity 60.6%, positive predictive value 92.7% and negative predictive value 47.6%). The score discriminated well with a ROC curve area of 0.837 (95% confidence interval [0.769 - 0.905]). CONCLUSIONS: This clinical prediction rule is a simple measure that may identify children who needed emergency endoscopy. A prospective study is required to validate our results and evaluate other clinical features that were insufficient for this analysis. PMID- 26895130 TI - Primary linitis plastica of the rectum. PMID- 26895132 TI - Syphilitic uveitis revealed by bilateral retinal occlusive vasculitis. PMID- 26895131 TI - Thyroid tuberculosis: a case report. PMID- 26895134 TI - Spectral-domain optical coherence tomography in macular edema associated with latanoprost. PMID- 26895133 TI - Granulosis cell tumor of coecum: about one case. PMID- 26895135 TI - Spectral-domain optical coherence tomography in macular edema associated with latanoprost. PMID- 26895136 TI - Correlation between Molecular Mobility and Physical Stability in Pharmaceutical Glasses. AB - We investigated a possible correlation between molecular mobility and physical stability in glassy celecoxib and indomethacin and identified the specific mobility mode responsible for physical instability (crystallization). In the glassy state, because the structural relaxation times are very long, the measurement was enabled by time domain dielectric spectroscopy. However, the local motions in the glassy state were characterized by frequency domain dielectric spectroscopy. Isothermal crystallization was monitored by powder X-ray diffractometry using either a laboratory source (supercooled state) or synchrotron source (glassy state). Structural (alpha) relaxation time correlated well with characteristic crystallization time in the supercooled state. On the other hand, a stronger correlation was observed between the Johari-Goldstein (beta) relaxation time and physical instability in the glassy state but not with structural relaxation time. These results suggest that Johari-Goldstein relaxation is a potential predictor of physical instability in the glassy state of these model systems. PMID- 26895137 TI - In Situ Synthesis and Characterization of Ge Embedded Electrospun Carbon Nanostructures as High Performance Anode Material for Lithium-Ion Batteries. AB - While active materials based on germanium (Ge) are considered as a promising alternative anodic electrode due to their relatively high reversible capacity and excellent lithium-ion diffusivity, the quite unstable structural/electrochemical stability and severe volume expansion or pulverization problems of Ge electrodes remain a considerable challenge in lithium ion batteries (LIBs). Here, we present the development of Ge embedded in one-dimensional carbon nanostructures (Ge/CNs) synthesized by the modified in situ electrospinning technique using a mixed electrospun solution consisting of a Ge precursor as an active material source and polyacrylonitrile (PAN) as a carbon source. The as-prepared Ge/CNs exhibit superior lithium ion behavior properties, i.e., highly reversible specific capacity, rate performance, Li ion diffusion coefficient, and superior cyclic stability (capacity retention: 85% at 200 mA g(-1)) during Li alloying/dealloying processes. These properties are due to the high electrical conductivity and unique structures containing well-embedded Ge nanoparticles (NPs) and a one dimensional carbon nanostructure as a buffer medium, which is related to the volume expansion of Ge NPs. Thus, it is expected that the Ge/CNs can be utilized as a promising alternative anodic material in LIBs. PMID- 26895138 TI - An exploration of the feasibility, acceptability, and effectiveness of professional, multitasked community health workers in Tanzania. AB - Despite four decades of global experience with community-based primary health care, the strategic details of community health worker (CHW) recruitment, training, compensation, and deployment remain the subject of continuing discussion and debate. Responsibilities and levels of clinical expertise also vary greatly, as well as contrasting roles of public- versus private-sector organisations as organisers of CHW effort. This paper describes a programme of implementation research in Tanzania, known as the Connect Project, which aims to guide national policies with evidence on the impact and process of deploying of paid, professional CHWs. Connect is a randomised-controlled trial of community exposure to CHW integrated primary health-care services. A qualitative appraisal of reactions to CHW implementation of community stakeholders, frontline workers, supervisors, and local managers is reviewed. Results highlight the imperative to plan and implement CHW programmes as a component of a broader, integrated effort to strengthen the health system. Specifically, the introduction of a CHW programme in Tanzania should draw upon community structures and institutions and strengthen mechanisms to sustain their participation in primary health care. This should be coordinated with efforts to address poorly functioning logistics and supervisory systems and human resource and management challenges. PMID- 26895139 TI - Chromosome condensation and decondensation during mitosis. AB - During eukaryotic cell division, nuclear chromatin undergoes marked changes with respect to shape and degree of compaction. Although already significantly compacted during interphase, upon entry into mitosis chromatin further condenses and individualizes to discrete chromosomes that are captured and moved independently by the mitotic spindle apparatus. Once segregated by the spindle, chromatin decondenses to re-establish its interphase structure competent for DNA replication and transcription. Although cytologically described a long time ago, the underlying molecular mechanisms of mitotic chromatin condensation and decondensation are still ill-defined. Here we summarize our current knowledge of mitotic chromatin restructuring and recent progress in the field. PMID- 26895140 TI - Cycling in the nucleus: regulation of RNA 3' processing and nuclear organization of replication-dependent histone genes. AB - The histones which pack new DNA during the S phase of animal cells are made from mRNAs that are cleaved at their 3' end but not polyadenylated. Some of the factors used in this reaction are unique to it while others are shared with the polyadenylation process that generates all other mRNAs. Recent work has begun to shed light on how the cell manages the assignment of these common components to the two 3' processing systems, and how it achieves their cell cycle-regulation and recruitment to the histone pre-mRNA. Moreover, recent and older findings reveal multiple connections between the nuclear organization of histone genes, their transcription and 3' end processing as well as the control of cell proliferation. PMID- 26895142 TI - Why do the outer membrane proteins OmpF from E. coli and OprP from P. aeruginosa prefer trimers? Simulation studies. AB - Porins are water-filled protein channels across the outer membrane of gram negative bacteria. They facilitate the uptake of nutrients and essential ions. Solutes are filtered by a constriction loop L3 at the mid of a pore. Porins are heat-stable and resistant to toxic agents and detergents. Most porins are trimer, but no clear explanation why trimeric form is preferable. In this work, we thus studied effects of oligomerization on porin structure and function in microscopic detail. A well-studied OmpF (general porin from Escherichia coli) and well characterised OprP (phosphate-specific pore from Pseudomonas aeruginosa) are used as samples from 2 types of porins found in gram-negative bacteria. MD simulations of trimeric and monomeric pores in pure water and 1M NaCl solution were performed. With a salt solution, the external electric field was applied to mimic a transmembrane potential. Expectedly, OprP is more stable than OmpF. Interestingly, being a monomer turns OmpF into an anion-selective pore. The dislocation of D113's side chain on L3 in OmpF causes the disruption of cation pathway resulting in the reduction of cation influx. In contrast, OprP's structure and function are less dependent on oligomeric states. Both monomeric and trimeric OprP can maintain their anion selectivity. Our findings suggest that trimerization is crucial for both structure and function of general porin OmpF, whereas being trimer in substrate-specific channel OprP supports a pore function. PMID- 26895141 TI - Squish and squeeze-the nucleus as a physical barrier during migration in confined environments. AB - From embryonic development to cancer metastasis, cell migration plays a central role in health and disease. It is increasingly becoming apparent that cells migrating in three-dimensional (3-D) environments exhibit some striking differences compared with their well-established 2-D counterparts. One key finding is the significant role the nucleus plays during 3-D migration: when cells move in confined spaces, the cell body and nucleus must deform to squeeze through available spaces, and the deformability of the large and relatively rigid nucleus can become rate-limiting. In this review, we highlight recent findings regarding the role of nuclear mechanics in 3-D migration, including factors that govern nuclear deformability, and emerging mechanisms by which cells apply cytoskeletal forces to the nucleus to facilitate nuclear translocation. Intriguingly, the 'physical barrier' imposed by the nucleus also impacts cytoplasmic dynamics that affect cell migration and signaling, and changes in nuclear structure resulting from the mechanical forces acting on the nucleus during 3-D migration could further alter cellular function. These findings have broad relevance to the migration of both normal and cancerous cells inside living tissues, and motivate further research into the molecular details by which cells move their nuclei, as well as the consequences of the mechanical stress on the nucleus. PMID- 26895144 TI - A technique for large-area position-controlled growth of GaAs nanowire arrays. AB - We demonstrate a technique for fabricating position-controlled, large-area arrays of vertical semiconductor nanowires (NWs) with adjustable periods and NW diameters. In our approach, a Au-covered GaAs substrate is first coated with a thin film of photoresponsive azopolymer, which is exposed twice to a laser interference pattern forming a 2D surface relief grating. After dry etching, an array of polymer islands is formed, which is used as a mask to fabricate a matrix of gold particles. The Au particles are then used as seeds in vapour-liquid-solid growth to create arrays of vertical GaAs NWs using metalorganic vapour phase epitaxy. The presented technique enables producing NWs of uniform size distribution with high throughput and potentially on large wafer sizes without relying on expensive lithography techniques. The feasibility of the technique is demonstrated by arrays of vertical NWs with periods of 255-1000 nm and diameters of 50-80 nm on a 2 * 2 cm area. The grown NWs exhibit high long range order and good crystalline quality. Although only GaAs NWs were grown in this study, in principle, the presented technique is suitable for any material available for Au seeded NW growth. PMID- 26895143 TI - Initial Evaluation of the Pediatric PROMIS(r) Health Domains in Children and Adolescents With Sickle Cell Disease. AB - BACKGROUND: The Patient Reported Outcomes Measurement Information System (PROMIS(r)) has developed pediatric self-report scales measuring several unidimensional health attributes (domains) suitable for use in clinical research, but these measures have not yet been validated in sickle cell disease (SCD). PROCEDURE: A convenience sample of SCD children, aged 8-17 years, from two sickle cell programs was recruited at routine clinic visits, including some for hydroxyurea monitoring or monthly transfusions. Children completed PROMIS pediatric items using an online data collection platform, the PROMIS Assessment Center Web site. RESULTS: A total of 235 participants (mean age 12.5 +/- 2.8 years, 49.8% female) participated in the study. Adolescents (ages 12-17 years) reported significantly higher pain interference and depressive symptoms, and worse lower extremity physical functioning domain scores compared to younger children (ages 8-11 years). Female participants reported significantly higher pain interference, fatigue, and depressive symptoms, and worse lower extremity physical functioning domain scores compared with their male counterparts. Participants with hip or joint problems that limited usual activities reported significantly higher pain, fatigue, and depressive symptoms scores, and worse upper/lower extremity physical functioning scores as did participants who had experienced sickle pain in the previous 7 days. CONCLUSIONS: PROMIS pediatric measures are feasible in a research setting and identify expected differences in known group comparisons in a sample of SCD children. The large domain score differences between those with or without SCD-related complications suggest the potential usefulness of these measures in clinical research, but further validation studies are needed, particularly in clinical practice settings. PMID- 26895146 TI - Barriers to knowledge sharing in Chinese healthcare referral services: an emergent theoretical model. AB - BACKGROUND: This paper reports on a research study that aims to identify and explain barriers to knowledge sharing (KS) in the provision of healthcare referral services in Chinese healthcare organisations. DESIGN: An inductive case study approach was employed, in which 24 healthcare professionals and workers from four healthcare organisations in the province of Hubei, Central China, were interviewed using semi-structured scripts. RESULTS: Through data analysis, 14 KS barriers emerged in four main themes: interpersonal trust barriers, communication barriers, management and leadership barriers, and inter-institutional barriers. A cause-consequence analysis of the identified barriers revealed that three of them are at the core of the majority of problems, namely, the absence of national and local policies for inter-hospital KS, lack of a specific hospital KS requirement, and lack of mutual acquaintance. CONCLUSIONS: To resolve KS problems, it is of great importance that healthcare governance agencies, both at the national and regional levels, take leadership in the process of KS implementation by establishing specific and strong policies for inter-institutional KS in the referral process. This paper raises important issues that exceed academic interests and are important to healthcare professionals, hospital managers, and Information communication technology (ICT) managers in hospitals, as well as healthcare politicians and policy makers. PMID- 26895145 TI - Beliefs, perceptions and health-seeking behaviours in relation to cervical cancer: a qualitative study among women in Uganda following completion of an HPV vaccination campaign. AB - BACKGROUND: Cervical cancer remains a leading cause of morbidity and mortality in Uganda. Despite earlier information campaigns to introduce human papilloma virus (HPV) vaccination, which also targeted cervical cancer, misinterpretation and misunderstanding of the subject remain high. Women in Uganda present with cervical cancer at an advanced stage due to poor health-seeking behaviours, with an associated high mortality rate. This project explored beliefs, attitudes, perceptions, and health-seeking behaviours in relation to cervical cancer among women in Uganda after an HPV vaccination project had been rolled out. DESIGN: A qualitative study design was used, with six focus group discussions (FGDs) that included 36 women, aged 25-49 years, with no previous history of cervical cancer symptoms or diagnosis. The women were interviewed in February and March 2013. The transcribed data was analysed using content analysis. RESULTS: Three themes emerged: feeling unprotected and unsafe, misbelief and wondering about cervical cancer, and fear of the testing procedure. Participating women had heard of cervical cancer but preferred to wait to access cervical cancer screening until symptom debut. CONCLUSIONS: There are still barriers to cervical cancer screening among women in Uganda, where there is a need for culture-specific, sensitive information and interventions to address the issues of improving the cervical cancer screening uptake among these women. Societal context needs to be taken into account when implementing community-based health education. PMID- 26895147 TI - Risk factors associated with neonatal deaths: a matched case-control study in Indonesia. AB - BACKGROUND: Similar to global trends, neonatal mortality has fallen only slightly in Indonesia over the period 1990-2010, with a high proportion of deaths in the first week of life. OBJECTIVE: This study aimed to identify risk factors associated with neonatal deaths of low and normal birthweight infants that were amenable to health service intervention at a community level in a relatively poor province of Indonesia. DESIGN: A matched case-control study of neonatal deaths reported from selected community health centres (puskesmas) was conducted over 10 months in 2013. Cases were singleton births, born by vaginal delivery, at home or in a health facility, matched with two controls satisfying the same criteria. Potential variables related to maternal and neonatal risk factors were collected from puskesmas medical records and through home visit interviews. A conditional logistic regression was performed to calculate odds ratios using the clogit procedure in Stata 11. RESULTS: Combining all significant variables related to maternal, neonatal, and delivery factors into a single multivariate model, six factors were found to be significantly associated with a higher risk of neonatal death. The factors identified were as follows: neonatal complications during birth; mother noting a health problem during the first 28 days; maternal lack of knowledge of danger signs for neonates; low Apgar score; delivery at home; and history of complications during pregnancy. Three risk factors (neonatal complication at delivery; neonatal health problem noted by mother; and low Apgar score) were significantly associated with early neonatal death at age 0-7 days. For normal birthweight neonates, three factors (complications during delivery; lack of early initiation of breastfeeding; and lack of maternal knowledge of neonatal danger signs) were found to be associated with a higher risk of neonatal death. CONCLUSION: The study identified a number of factors amenable to health service intervention associated with neonatal deaths in normal and low birthweight infants. These factors include maternal knowledge of danger signs, response to health problems noted by parents in the first month, early initiation of breastfeeding, and delivery at home. Addressing these factors could reduce neonatal deaths in low resource settings. PMID- 26895148 TI - Measuring Progress on the Control of Porcine Reproductive and Respiratory Syndrome (PRRS) at a Regional Level: The Minnesota N212 Regional Control Project (Rcp) as a Working Example. AB - Due to the highly transmissible nature of porcine reproductive and respiratory syndrome (PRRS), implementation of regional programs to control the disease may be critical. Because PRRS is not reported in the US, numerous voluntary regional control projects (RCPs) have been established. However, the effect of RCPs on PRRS control has not been assessed yet. This study aims to quantify the extent to which RCPs contribute to PRRS control by proposing a methodological framework to evaluate the progress of RCPs. Information collected between July 2012 and June 2015 from the Minnesota Voluntary Regional PRRS Elimination Project (RCP-N212) was used. Demography of premises (e.g. composition of farms with sows = SS and without sows = NSS) was assessed by a repeated analysis of variance. By using general linear mixed-effects models, active participation of farms enrolled in the RCP-N212, defined as the decision to share (or not to share) PRRS status, was evaluated and used as a predictor, along with other variables, to assess the PRRS trend over time. Additionally, spatial and temporal patterns of farmers' participation and the disease dynamics were investigated. The number of farms enrolled in RCP-N212 and its geographical coverage increased, but the proportion of SS and NSS did not vary significantly over time. A significant increasing (p<0.001) trend in farmers' decision to share PRRS status was observed, but with NSS producers less willing to report and a large variability between counties. The incidence of PRRS significantly (p<0.001) decreased, showing a negative correlation between degree of participation and occurrence of PRRS (p<0.001) and a positive correlation with farm density at the county level (p = 0.02). Despite a noted decrease in PRRS, significant spatio-temporal patterns of incidence of the disease over 3-weeks and 3-kms during the entire study period were identified. This study established a systematic approach to quantify the effect of RCPs on PRRS control. Despite an increase in number of farms enrolled in the RCP-N212, active participation is not ensured. By evaluating the effect of participation on the occurrence of PRRS, the value of sharing information among producers may be demonstrated, in turn justifying the existence of RCPs. PMID- 26895149 TI - Translational Medicine: A Requirement for Effective Health Care in the Future. PMID- 26895150 TI - The Catalonian Expert Patient Programme for Chagas Disease: An Approach to Comprehensive Care Involving Affected Individuals. AB - The Catalonian Expert Patient Programme on Chagas disease is a initiative, which is part of the Chronic Disease Programme. It aims to boost responsibility of patients for their own health and to promote self-care. The programme is based on nine sessions conducted by an expert patient. Evaluation was focusing in: habits and lifestyle/self-care, knowledge of disease, perception of health, self-esteem, participant satisfaction, and compliance with medical follow-up visits. Eighteen participants initiated the programme and 15 completed it. The participants were Bolivians. The 66.7 % of them had been diagnosed with chagas disease in Spain. The 100 % mentioned that they would participate in this activity again and would recommend it to family and friends. The knowledge about disease improve after sessions. The method used in the programme could serve as a key strategy in the field of comprehensive care for individuals with this disease. PMID- 26895151 TI - Subjective Social Status and Self-Reported Health Among US-born and Immigrant Latinos. AB - Subjective social status is associated with a range of health outcomes. Few studies have tested the relevance of subjective social status among Latinos in the U.S.; those that have yielded mixed results. Data come from the Latino subsample of the 2003 National Latino and Asian American Study (N = 2554). Regression models adjusted for socioeconomic and demographic factors. Stratified analyses tested whether nativity status modifies the effect of subjective social status on health. Subjective social status was associated with better health. Income and education mattered more for health than subjective social status among U.S.-born Latinos. However, the picture was mixed among immigrant Latinos, with subjective social status more strongly predictive than income but less so than education. Subjective social status may tap into stressful immigrant experiences that affect one's perceived self-worth and capture psychosocial consequences and social disadvantage left out by conventional socioeconomic measures. PMID- 26895152 TI - The Role of Ethnicity and Acculturation in Preoperative Distress in Parents of Children Undergoing Surgery. AB - This study examined the effects of acculturation on anxiety and stress in Latino and non-Latino white parents of children undergoing outpatient surgery. Participants included 686 parent-child dyads from four major children's hospitals in the United States. Latino parents who grew up in the U.S. reported higher levels of anxiety (p = 0.009) and stress (p < 0.001) compared to parents who grew up in a Latin American country. Additionally, English-speaking Latino parents reported higher anxiety and stress compared to both Spanish-speaking Latino and non-Latino white parents (p's < 0.05), whereas Spanish-speaking Latino and non Latino white parents reported similar levels of stress and anxiety. Results of the current study were consistent with the immigrant health paradox in that more acculturated Latino parents reported higher levels of anxiety and stress than less acculturated Latino and non-Latino white parents, supporting the need for culturally tailored interventions in the perioperative environment. PMID- 26895153 TI - AIDS Service Organization Access Among African, Caribbean and Other Black Residents of an Average Canadian City. AB - Due to heightened vulnerability to HIV/AIDS, African, Caribbean and Black (ACB) communities are priority groups for prevention and intervention services in Canada. However, it is not clear which factors may affect ACB communities' access to these services. We evaluated access to the local AIDS service organization (ASO) in Middlesex-London by using data from the Black, African and Caribbean Canadian Health Study. Modified Poisson regression was used to obtain prevalence risk ratios for factors associated with three measures of access: familiarity with the ASO, willingness to access, and realized access. In adjusted analyses, older ACB community members were more likely to be familiar with the ASO, willing to access it, and have actually gone there. Canadian-born participants were less likely to have been to the ASO than recent immigrants. These results have implications for reaching specific segments of ACB communities for HIV/AIDS related services in Canada. PMID- 26895154 TI - Inhibition of AXUD1 attenuates compression-dependent apoptosis of cementoblasts. AB - OBJECTIVES: Root resorptions are common undesirable side effects of orthodontic treatment. In most patients, these defects are repaired by cementoblasts. However, in 1-5 % of patients, the repair fails. The repair mechanism is not well understood. Apoptosis of cementoblasts might contribute to an impaired repair of root resorptions induced by orthodontic forces. MATERIALS AND METHODS: To gain insight into putative molecular pathways leading to compression-induced apoptosis of human primary cementoblasts (HPCBs), three independent cell populations were subjected to compressive loading at 5, 20, and 30 g/cm2 for 1, 6, and 10 h. The mRNA expression of AXUD1, a novel pro-apoptotic gene, was monitored by quantitative reverse transcription PCR (qRT-PCR). To identify a possible function in compression-dependent apoptosis, AXUD1 was silenced in cementoblasts using an siRNA approach. Apoptosis of cementoblasts was measured by annexin V staining and flow cytometry. The phosphorylation of c-Jun-N-terminal kinases (JNKs) was investigated by Western blotting. RESULTS: AXUD1 was significantly induced in a time- and force-dependent manner. The rate of apoptotic HPCBs increased by 20-40 % after 10 h of compression (30 g/cm2). Phosphorylation of JNKs was detected after 10 h at 30 g/cm2. SiRNA-mediated knockdown of AXUD1 led to decreased phosphorylation of JNKs and reduced apoptosis rates in compressed HPCBs. CONCLUSIONS: Compression-induced apoptosis of HPCBs is mediated by AXUD1 via a JNK-dependent pathway. CLINICAL RELEVANCE: AXUD1-dependent apoptosis of human cementoblasts might contribute to an impaired repair of root resorptions during orthodontic tooth movement. Further studies are needed to develop treatment strategies aiming to minimize root resorption during orthodontic tooth movement. PMID- 26895156 TI - Correction: Kicking against the PRCs--A Domesticated Transposase Antagonises Silencing Mediated by Polycomb Group Proteins and Is an Accessory Component of Polycomb Repressive Complex 2. PMID- 26895155 TI - Neurons are the Primary Target Cell for the Brain-Tropic Intracellular Parasite Toxoplasma gondii. AB - Toxoplasma gondii, a common brain-tropic parasite, is capable of infecting most nucleated cells, including astrocytes and neurons, in vitro. Yet, in vivo, Toxoplasma is primarily found in neurons. In vitro data showing that interferon gamma-stimulated astrocytes, but not neurons, clear intracellular parasites suggest that neurons alone are persistently infected in vivo because they lack the ability to clear intracellular parasites. Here we test this theory by using a novel Toxoplasma-mouse model capable of marking and tracking host cells that directly interact with parasites, even if the interaction is transient. Remarkably, we find that Toxoplasma shows a strong predilection for interacting with neurons throughout CNS infection. This predilection remains in the setting of IFN-gamma depletion; infection with parasites resistant to the major mechanism by which murine astrocytes clear parasites; or when directly injecting parasites into the brain. These findings, in combination with prior work, strongly suggest that neurons are not incidentally infected, but rather they are Toxoplasma's primary in vivo target. PMID- 26895157 TI - Exposure and inequality for select urban air pollutants in the Tampa Bay area. AB - Air pollution exposure has been linked to numerous adverse health effects, with some disadvantaged subgroups disproportionately burdened. The objective of this work was to characterize distributions of emissions and concentrations of a few important urban air toxics at high spatiotemporal resolution in order to assess exposure and inequality. Benzene, 1,3-butadiene, formaldehyde, and acetaldehyde were the focus pollutants, with oxides of nitrogen (NOx) estimated for comparisons. Primary pollutant emissions were estimated for the full spectrum of source types in the Tampa area using a hybrid approach that is most detailed for major roadways and includes hourly variations in vehicle speed. Resultant pollutant concentrations were calculated using the CALPUFF dispersion model, and combined with CMAQ model output to account for secondary formation of formaldehyde and acetaldehyde. Census demographic data were applied to estimate residential pollution exposures and inequality among population subgroups. Estimated concentrations of benzene, 1,3-butadiene, and NOx were generally higher in urban areas and lower in rural areas. Exposures to these pollutants were disproportionately high for subgroups characterized as black, Hispanic and low income (annual household income less than $20,000). For formaldehyde and acetaldehyde, the patterns of concentration and exposure were largely reversed. Results suggest that disparities in exposure depend on pollutant type. PMID- 26895158 TI - Localized delivery of methylprednisolone sodium succinate with polymeric nanoparticles in experimental injured spinal cord model. AB - With important social and economic consequences, spinal cord injuries (SCIs) still exist among major health problems. Although many therapeutic agents and methods investigated for the treatment of acute SCI, only high dose methylprednisolone (MP) is being used currently in practice. Due to the serious side effects, high dose systemic MP administration after SCI is a critical issue that is mostly considered controversial. In our study, it is aimed to develop a nanoparticle-gel combined drug delivery system for localization of MP on trauma site and eliminating dose-dependent side effects by lowering the administered dose. For this purpose, methyl prednisolone sodium succinate (MPSS) loaded polycaprolactone based nanoparticles were developed and embedded in an implantable fibrin gel. The effects of MPSS delivery system are evaluated on an acute SCI rat model, by quantification the levels of three inflammatory cytokines (interleukin-1beta, interleukin-6 and caspase-3) and assessment of the damage on ultrastructural level by transmission electron microscopy. Developed NP-gel system showed very similar results with systemic high dose of MPSS. It is believed that developed system may be used as a tool for the safe and effective localized delivery of several other therapeutic molecules on injured spinal cord cases. PMID- 26895159 TI - Functional evaluation of an iridotomy in primary angle closure eyes. AB - OBJECTIVE: To evaluate the functional efficacy of an iridotomy in primary angle closure (PAC) eyes by measuring IOP responses to provocative tests before and after iridotomy. DESIGN: Prospective cohort study. SUBJECTS: 50 consecutive adult patients, 40-60 years of age, having primary angle closure. METHODS: Clinical examination, perimetry, biometry and ultrasound biomicroscopy of the angle were done. A darkroom prone provocative test (DRPPT), a mydriatic test and a Valsalva maneuver were performed before and after the iridotomy. MAIN OUTCOME MEASURES: IOP change in response to the provocative tests before and after iridotomy, and correlation with baseline parameters. RESULTS: IOP at baseline and after iridotomy was 14.4 +/- 2.7 mmHg and 14.3 +/- 2.6 mmHg, respectively (p = 0.)83. There was no significant change on diurnal phasing before and after an iridotomy (p = 0.)11. The mean IOP rise was 5.9 +/- 3.7 mmHg on the DRPPT, 4.3 +/- 3.5 mmHg on the Mydriatic test and 9.1 +/- 4.9 mmHg on the Valsalva maneuver, and was reduced significantly to 3.2 +/- 2.1 mmHg, 2.3 +/- 1.8 and 6.4 +/- 3.5, respectively(p < 0.001 for all tests). The decrease in pupillary block component for all 50 eyes was 46.5 % for the mydriatic test, 45.8 % for the DRPPT and 29.7 % for the Valsalva maneuver. PAC eyes positive on the DRPPT and mydriatic test prior to an iridotomy became negative after laser iridotomy in 75.9 and 84.6 % eyes, respectively, but on the Valsalva maneuver, only 23.8 % became negative. After iridotomy, eyes that continued to be positive on the mydriatic test had a significantly thicker lens (p = 0.02), decreased TCPD (p = 0.014) and narrower trabecular-iris angle (p = 0.048). On the DRPPT, they had a thicker lens (p = 0.03), shorter iris thickness (p = 0.025) and TCPD (p = 0.032), and on the Valsalva maneuver, they had a narrower scleral-ciliary process angle (SCPA; p = 0.019) and shorter TCPD (p = 0.015). CONCLUSIONS: This comprehensive functional evaluation of laser iridotomy in early PAC eyes showed a significant reduction in the pupillary block component of IOP response to provocative testing, possibly decreasing IOP fluctuations over time. An iridotomy does not, however, significantly change mean IOP or diurnal phasing of IOP in PAC eyes. Eyes with a very narrow angle or a thick lens may continue to have angle closure due to other pathomechanisms for angle closure. PMID- 26895160 TI - Effect of hole size on fluid dynamics of a posterior-chamber phakic intraocular lens with a central perforation by using computational fluid dynamics. AB - BACKGROUND: A modified implantable collamer lens (ICL) with a central hole with a diameter of 0.36 mm, referred to as a hole-ICL, was created to improve aqueous humour circulation. The aim of this study is to investigate the ideal hole size in a hole-ICL from the standpoint of the fluid dynamic characteristics of the aqueous humour using computational fluid dynamics. METHODS: Fluid dynamics simulation using an ICL was performed with thermal-hydraulic analysis software FloEFD V 12.2 (Mentor Graphics Corp.). In the simulation, three-dimensional eye models based on a modified Liou-Brennan model eye with a conventional ICL (Model ICM, Staar Surgical) and a hole-ICL were used. The hole-ICL was -9.0 dioptres (D) and 12.0 mm in length, with an optic zone of 5.5 mm. The vaulting was 0.50 mm. The quantity of aqueous humour produced by the ciliary body was set at 2.80 MUL/min. Flow distribution between the anterior surface of the crystalline lens and the posterior surface of the ICL was calculated, and trajectory analysis was performed. RESULTS: With an increase in the central hole size, the velocity of the aqueous humour increased, with the peak velocity occurring at a diameter of approximately 0.4 mm. Once the diameter had increased above 0.4 mm, the velocity then decreased. The velocity difference between the cases of a central hole size of 0.1 mm and 0.2 mm was significant. CONCLUSION: The desirable central hole size was 0.2 mm or larger in terms of flow dynamics. The current model, based on a central hole size of 0.36 mm, was close to ideal. The optimisation of the hole size should be performed based on results from a long-term clinical study so as to analyse the incidence rate of secondary cataract and optical performance. PMID- 26895161 TI - Averting the Legacy of Kidney Disease--Focus on Childhood. AB - World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, while only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood. PMID- 26895163 TI - [Absolute certainty cannot exist]. PMID- 26895162 TI - A Systematic Approach towards Optimizing a Cohabitation Challenge Model for Infectious Pancreatic Necrosis Virus in Atlantic Salmon (Salmo salar L.). AB - A cohabitation challenge model was developed for use in evaluating the efficacy of vaccines developed against infectious pancreatic necrosis virus (IPNV) in Atlantic salmon (Salmo salar L) using a stepwise approach. The study involved identifying a set of input variables that were optimized before inclusion in the model. Input variables identified included the highly virulent Norwegian Sp strain NVI015-TA encoding the T217A221 motif having the ability to cause >90% mortality and a hazard risk ratio of 490.18 (p<0.000) for use as challenge virus. The challenge dose was estimated at 1x10(7) TCID50/mL per fish while the proportion of virus shedders was estimated at 12.5% of the total number of fish per tank. The model was designed based on a three parallel tank system in which the Cox hazard proportional regression model was used to estimate the minimum number of fish required to show significant differences between the vaccinated and control fish in each tank. All input variables were optimized to generate mortality >75% in the unvaccinated fish in order to attain a high discriminatory capacity (DC) between the vaccinated and control fish as a measure of vaccine efficacy. The model shows the importance of using highly susceptible fish to IPNV in the optimization of challenge models by showing that highly susceptible fish had a better DC of differentiating vaccine protected fish from the unvaccinated control fish than the less susceptible fish. Once all input variables were optimized, the model was tested for its reproducibility by generating similar results from three independent cohabitation challenge trials using the same input variables. Overall, data presented here show that the cohabitation challenge model developed in this study is reproducible and that it can reliably be used to evaluate the efficacy of vaccines developed against IPNV in Atlantic salmon. We envision that the approach used here will open new avenues for developing optimal challenge models for use in evaluating the efficacy of different vaccines used in aquaculture. PMID- 26895164 TI - Editors' Notes. PMID- 26895165 TI - Beyond Individual Leader Development: Cultivating Collective Capacities. AB - This chapter addresses the overemphasis on individual-leader development in leadership education, offering insights and pragmatic approaches for advancing collective leadership focused on social and political change. PMID- 26895166 TI - Beyond Service: Equipping Change Agents Through Community Leadership Education. AB - This chapter describes one university's effort to integrate civic engagement programs and leadership education curriculum, informed by empowerment theory, servant leadership, and community organizing methodologies. PMID- 26895168 TI - Leadership in Solidarity: Notions of Leadership Through Critical Participatory Action Research With Young People and Adults. AB - The authors trace the connections between multigenerational participatory action research and relational approaches to shared leadership, illustrating how the collective production of knowledge through research builds youth leadership capacity. PMID- 26895167 TI - Radically Healing Black Lives: A Love Note to Justice. AB - This chapter describes how present conditions in Black communities have fostered the development of new modes of youth leadership that focus on hope, love, and joy, and are ultimately restorative and redemptive. PMID- 26895169 TI - Summer in the City: Cultivating Political Agents in Boston Out-of-School-Time Programs. AB - Diverse urban youth need a wide range of program opportunities and formats to develop their own sense of political agency and leadership. One size does not fit all. PMID- 26895170 TI - Educating for Global Leadership: A North-South Collaboration. AB - This chapter examines two global education programs in higher education, one in the global North and the other in the global South to explore the shift from command to community in leadership. PMID- 26895171 TI - International Perspectives on Youth Leadership Development Through Community Organizing. AB - This chapter details the ways youth community organizing strategies can inform leadership educators' approaches to engaging marginalized youth in leadership development for social change. PMID- 26895172 TI - Inverse PCR and Quantitative PCR as Alternative Methods to Southern Blotting Analysis to Assess Transgene Copy Number and Characterize the Integration Site in Transgenic Woody Plants. AB - One of the major unanswered questions with respect to the commercial use of genetic transformation in woody plants is the stability of the transgene expression over several decades within the same individual. Gene expression is strongly affected by the copy number which has been integrated into the plant genome and by the local DNA features close to the integration sites. Because woody plants cannot be subjected to selfing or backcrossing to modify the transgenic allelic structure without affecting the valuable traits of the cultivar, molecular characterization of the transformation event is therefore crucial. After assessing the transgene copy number of a set of apple transgenic clones with Southern blotting, we describe two alternative methods: the first is based on inverse PCR (i-PCR) and the second on the quantitative PCR (q-PCR). The methods produced comparable results with the exception of the data regarding a high copy number clone, but while the q-PCR-based system is rapid and easily adaptable to high throughput systems, the i-PCR-based method can provide information regarding the transformation event and the characteristics of the sequences flanking the transgenic construct. PMID- 26895173 TI - Uncertainty in the Life Cycle Greenhouse Gas Emissions from U.S. Production of Three Biobased Polymer Families. AB - Interest in biobased products has been motivated, in part, by the claim that these products have lower life cycle greenhouse gas (GHG) emissions than their fossil counterparts. This study investigates GHG emissions from U.S. production of three important biobased polymer families: polylactic acid (PLA), polyhydroxybutyrate (PHB) and bioethylene-based plastics. The model incorporates uncertainty into the life cycle emission estimates using Monte Carlo simulation. Results present a range of scenarios for feedstock choice (corn or switchgrass), treatment of coproducts, data sources, end of life assumptions, and displaced fossil polymer. Switchgrass pathways generally have lower emissions than corn pathways, and can even generate negative cradle-to-gate emissions if unfermented residues are used to coproduce energy. PHB (from either feedstock) is unlikely to have lower emissions than fossil polymers once end of life emissions are included. PLA generally has the lowest emissions when compared to high emission fossil polymers, such as polystyrene (mean GHG savings up to 1.4 kg CO2e/kg corn PLA and 2.9 kg CO2e/kg switchgrass PLA). In contrast, bioethylene is likely to achieve the greater emission reduction for ethylene intensive polymers, like polyethylene (mean GHG savings up to 0.60 kg CO2e/kg corn polyethylene and 3.4 kg CO2e/kg switchgrass polyethylene). PMID- 26895174 TI - Trimethylamine stimulated and dissolved organic matter inhibited methane production in sediment from the Poyang Lake, China. AB - Methane (CH4) emitted from wetlands contributes significantly to the greenhouse effect. The Poyang Lake, the largest freshwater lake in China, is fed by five rivers and connects to the Yangtze River. The area of the lake fluctuates dramatically between drawdown and flood periods with large areas of wetlands. In order to understand the CH4 production capacity and factors that influence CH4 production in the wetland, a static closed chamber combined with a gas chromatograph technique was used to investigate the influence of substrates and electron acceptors on methanogenesis. The results showed that CH4 production capacity of sediments from the Poyang Lake was [Formula: see text] and it was stimulated by trimethylamine (TMA) to a great extent. Incubation temperature played a vital role on CH4 production in sediments and the optimum temperature for methanogenesis was 35 degrees C. Minimum CH4 production capacity occurred with the addition of FeCl3, and the inhibitory effects of electron acceptors decreased in the sequence: FeCl3 > MnO2 > DOM > Fe2O3. In this study, DOM was demonstrated as one of the inhibitors to methanogenesis and TMA was the main substrate of methanogens in the sediments of the Poyang Lake whose pH value is 7.83. PMID- 26895176 TI - An alternative approach to intragastric balloon retrieval. PMID- 26895177 TI - Nature of Mesoscopic Organization in Protic Ionic Liquid-Alcohol Mixtures. AB - The mesoscopic morphology of mixtures of ethylammonium nitrate, a protic ionic liquid, and n-pentanol is explored for the first time using small angle X-ray scattering as a function of concentration and temperature. Both compounds are amphiphilic and characterized by an extended hydrogen bonding network; however, though macroscopically homogeneous, their mixtures are highly heterogeneous at the mesoscopic spatial scales. Previous structural studies rationalized similar features in related mixtures proposing the existence of large aggregates or micelle- and/or microemulsion-like structures. Here we show that a detailed analysis of the present concentration and temperature resolved experimental data set supports a structural scenario where the mesoscopic heterogeneities are the due to density fluctuations that are precursors of liquid-liquid phase separation. Accordingly no existence of structurally organized aggregates (such as micellar or microemulsion aggregates) is required to account for the mesoscopic heterogeneities detected in this class of binary mixtures. PMID- 26895175 TI - Genome-Wide Discovery of Long Non-Coding RNAs in Rainbow Trout. AB - The ENCODE project revealed that ~70% of the human genome is transcribed. While only 1-2% of the RNAs encode for proteins, the rest are non-coding RNAs. Long non coding RNAs (lncRNAs) form a diverse class of non-coding RNAs that are longer than 200 nt. Emerging evidence indicates that lncRNAs play critical roles in various cellular processes including regulation of gene expression. LncRNAs show low levels of gene expression and sequence conservation, which make their computational identification in genomes difficult. In this study, more than two billion Illumina sequence reads were mapped to the genome reference using the TopHat and Cufflinks software. Transcripts shorter than 200 nt, with more than 83 100 amino acids ORF, or with significant homologies to the NCBI nr-protein database were removed. In addition, a computational pipeline was used to filter the remaining transcripts based on a protein-coding-score test. Depending on the filtering stringency conditions, between 31,195 and 54,503 lncRNAs were identified, with only 421 matching known lncRNAs in other species. A digital gene expression atlas revealed 2,935 tissue-specific and 3,269 ubiquitously-expressed lncRNAs. This study annotates the lncRNA rainbow trout genome and provides a valuable resource for functional genomics research in salmonids. PMID- 26895179 TI - Pharmacological Therapy of Bronchial Asthma: The Role of Biologicals. AB - Bronchial asthma is a heterogeneous, complex, chronic inflammatory and obstructive pulmonary disease driven by various pathways to present with different phenotypes. A small proportion of asthmatics (5-10%) suffer from severe asthma with symptoms that cannot be controlled by guideline therapy with high doses of inhaled steroids plus a second controller, such as long-acting beta2 agonists (LABA) or leukotriene receptor antagonists, or even systemic steroids. The discovery and characterization of the pathways that drive different asthma phenotypes have opened up new therapeutic avenues for asthma treatment. The approval of the humanized anti-IgE antibody omalizumab for the treatment of severe allergic asthma has paved the way for other cytokine-targeting therapies, particularly those targeting interleukin (IL)-4, IL-5, IL-9, IL-13, IL-17, and IL 23 and the epithelium-derived cytokines IL-25, IL-33, and thymic stromal lymphopoietin. Knowledge of the molecular basis of asthma phenotypes has helped, and continues to help, the development of novel biologicals that target a diverse array of phenotype-specific molecular targets in patients suffering from severe asthma. This review summarizes potential therapeutic approaches that are likely to show clinical efficacy in the near future, focusing on biologicals as promising novel therapies for severe asthma. PMID- 26895180 TI - Oroxylin A Inhibits Allergic Airway Inflammation in Ovalbumin (OVA)-Induced Asthma Murine Model. AB - Oroxylin A, a natural flavonoid isolated from the medicinal herb Scutellaria baicalensis Georgi, has been reported to have anti-inflammatory property. In this study, we aimed to investigate the protective effects and mechanism of oroxylin A on allergic inflammation in OVA-induced asthma murine model. BABL/c mice were sensitized and airway-challenged with OVA to induce asthma. Oroxylin A (15, 30, and 60 mg/kg) was administered by oral gavage 1 h before the OVA treatment on day 21 to 23. The results showed that oroxylin A attenuated OVA-induced lung histopathologic changes, airway hyperresponsiveness, and the number of inflammatory cells. Oroxylin A also inhibited the levels of IL-4, IL-5, IL-13, and OVA-specific IgE in BALF. Furthermore, oroxylin A significantly inhibited OVA induced NF-kappaB activation. In conclusion, these results suggested that oroxylin A inhibited airway inflammation in OVA-induced asthma murine model by inhibiting NF-kappaB activation. These results suggested that oroxylin A was a potential therapeutic drug for treating allergic asthma. PMID- 26895181 TI - Expression of emotions related to the experience of cancer in younger and older Arab breast cancer survivors. AB - OBJECTIVES: Researchers have suggested that older adults express less negative emotions. Yet, emotional expression patterns in older and younger breast cancer survivors, have barely been examined. This study aimed to explore types and intensity of negative and positive emotional expression related to the breast cancer experience by younger and older Arab breast cancer survivors. DESIGN: Participants were 20 younger (aged 32-50) and 20 older (aged 51-75) Muslim and Christian Arab breast cancer survivors (stages I-III), currently free of disease. Data were gathered through in-depth semi-structured interviews. Mixed methods analyses were conducted, including: (1) frequency analysis of participants' emotional expressions; (2) content analysis of emotional expressions, categorized according to negative and positive emotions. RESULTS: Three emotional expression modalities were revealed: (1) Succinct versus comprehensive accounts; (2) expression of emotions versus avoidance of emotions; (3) patterns of expression of positive emotions and a sense of personal growth. Younger women provided more detailed accounts about their illness experiences than older women. Older women's accounts were succinct, action-focused, and included more emotion-avoiding expressions than younger women. CONCLUSIONS: Understanding the relationships between emotional expression, emotional experience, and cancer survivors' quality of life, specifically of those from traditional communities, is necessary for developing effective psycho-social interventions. PMID- 26895178 TI - Developmental and Post-Eruptive Defects in Molar Enamel of Free-Ranging Eastern Grey Kangaroos (Macropus giganteus) Exposed to High Environmental Levels of Fluoride. AB - Dental fluorosis has recently been diagnosed in wild marsupials inhabiting a high fluoride area in Victoria, Australia. Information on the histopathology of fluorotic marsupial enamel has thus far not been available. This study analyzed the developmental and post-eruptive defects in fluorotic molar enamel of eastern grey kangaroos (Macropus giganteus) from the same high-fluoride area using light microscopy and backscattered electron imaging in the scanning electron microscope. The fluorotic enamel exhibited a brownish to blackish discolouration due to post-eruptive infiltration of stains from the oral cavity and was less resistant to wear than normally mineralized enamel of kangaroos from low-fluoride areas. Developmental defects of enamel included enamel hypoplasia and a pronounced hypomineralization of the outer (sub-surface) enamel underneath a thin rim of well-mineralized surface enamel. While the hypoplastic defects denote a disturbance of ameloblast function during the secretory stage of amelogenesis, the hypomineralization is attributed to an impairment of enamel maturation. In addition to hypoplastic defects, the fluorotic molars also exhibited numerous post-eruptive enamel defects due to the flaking-off of portions of the outer, hypomineralized enamel layer during mastication. The macroscopic and histopathological lesions in fluorotic enamel of M. giganteus match those previously described for placental mammals. It is therefore concluded that there exist no principal differences in the pathogenic mechanisms of dental fluorosis between marsupial and placental mammals. The regular occurrence of hypomineralized, opaque outer enamel in the teeth of M. giganteus and other macropodids must be considered in the differential diagnosis of dental fluorosis in these species. PMID- 26895182 TI - HIV Drug Resistance Mutations (DRMs) Detected by Deep Sequencing in Virologic Failure Subjects on Therapy from Hunan Province, China. AB - OBJECTIVE: Determine HIV drug resistance mutations (DRMs) prevalence at low and high levels in ART-experienced patients experiencing virologic failure (VF). METHODS: 29 subjects from 18 counties in Hunan Province that experienced VF were evaluated for the prevalence of DRMs (Stanford DRMs with an algorithm value >=15, include low-, intermediate and high-level resistance) by both Sanger sequencing (SS) and deep sequencing (DS) to 1% frequency levels. RESULTS: DS was performed on samples from 29 ART-experienced subjects; the median viral load 4.95*10(4) c/ml; 82.76% subtype CRF01_AE. 58 DRMs were detected by DS. 18 DRMs were detected by SS. Of the 58 mutations detected by DS, 40 were at levels <20% frequency (26 NNRTI, 12 NRTI and 2 PI) and the majority of these 95.00% (38/40) were not detected by standard genotyping. Of these 40 low-level DRMs, 16 (40%) were detected at frequency levels of 1-4% and 24 (60%) at levels of 5-19%. SS detected 15 of 17 (88.24%) DRMs at levels >= 20% that were detected by DS. The only variable associated with the detection of DRMs by DS was ART adherence (missed doses in the prior 7 days); all patients that reported missing a dose in the last 7 days had DRMs detected by DS. CONCLUSIONS: DS of VF samples from treatment experienced subjects infected with primarily AE subtype frequently identified Stanford HIVdb NRTI and NNRTI resistance mutations with an algorithm value 15. Low frequency level resistant variants detected by DS were frequently missed by standard genotyping in VF specimens from antiretroviral-experienced subjects. PMID- 26895183 TI - Serotonin transporter gene polymorphism in eating disorders: Data from a new biobank and META-analysis of previous studies. AB - Objectives Growing interest focuses on the association between 5-HTTLPR polymorphism and eating disorders (ED), but published findings have been conflicting. Methods The Italian BIO.VE.D.A. biobank provided 976 samples (735 ED patients and 241 controls) for genotyping. We conducted a literature search of studies published up to 1 April 2015, including studies reporting on 5HTTLPR genotype and allele frequencies in obesity and/or ED. We ran a meta-analysis, including data from BIO.VE.D.A. - comparing low and high-functioning genotype and allele frequencies in ED vs. CONTROLS: Results Data from 21 studies, plus BIO.VE.D.A., were extracted providing information from 3,736 patients and 2,707 controls. Neither low- nor high-functioning genotype frequencies in ED patients, with both bi- and tri-allelic models, differed from controls. Furthermore, neither low- nor high-functioning allele frequencies in ED or in BN, in both bi- and triallelic models, differed from control groups. After sensitivity analysis, results were the same in AN vs. CONTROLS: Results remained unaltered when investigating recessive and dominant models. Conclusions 5HTTLPR does not seem to be associated with ED in general, or with AN or BN in particular. Future studies in ED should explore the role of ethnicity and psychiatric comorbidity as a possible source of bias. PMID- 26895184 TI - Length variants of the ABCB1 3'-UTR and loss of miRNA binding sites: possible consequences in regulation and pharmacotherapy resistance. AB - AIM: To identify the exact length and possible length variations of the ABCB1 3' UTR as important regulatory site for miRNA interaction of this drug transporter and its possible contribution to drug resistance. MATERIALS & METHODS: 3'-RACE and various standard PCR experiments were performed using cDNA of different human cell lines and liver tissue. The abundance of 3'-UTR fragments was analyzed using quantitative RT-PCR. RESULTS: Five different ABCB1 3'-UTR length variants were identified. miRNA binding sites were located only on the three longer fragments. Imatinib-resistant leukemia cells expressed predominantly shorter 3'-UTRs, where miRNA binding sites are absent. CONCLUSION: Shortening of the ABCB1 3'-UTR causes loss of miRNA-dependent translational control leading to elevated ABCB1 protein levels. PMID- 26895185 TI - Work-related asthma among professional cleaning women. AB - The job of cleaning has developed dynamically as a working service, and women constitute the majority of all professional cleaning workers. Cleaners are at an increased risk of work-related asthma (WRA). This study characterizes work related respiratory symptoms reported by female cleaners, evaluates any associated factors of WRA, and shows diagnostic management of medical certification. The study group comprised 50 professional cleaning women referred to our Occupational Diseases Department due to suspicion of occupational asthma (OA). A questionnaire, skin prick tests, serum specific IgE antibodies, and specific inhalant challenge were performed in all of the participants. Work related asthma was recognized in 46% of symptomatic cleaners, of whom 15 were considered as having work-exacerbated asthma (WEA) and 8 as having OA. Sensitization to latex and disinfectants played an important role as a causative agent in OA of cleaners. PMID- 26895186 TI - Responses in Micro-Mineral Metabolism in Rainbow Trout to Change in Dietary Ingredient Composition and Inclusion of a Micro-Mineral Premix. AB - Responses in micro-mineral metabolism to changes in dietary ingredient composition and inclusion of a micro-mineral premix (Fe, Cu, Mn, Zn and Se) were studied in rainbow trout. In a 2 x 2 factorial design, triplicate groups of rainbow trout (initial weight: 20 g) were fed over 12 weeks at 17 degrees C a fishmeal-based diet (M) or a plant-ingredient based diet (V), with or without inclusion of a mineral premix. Trout fed the V vs. M diet had lower feed intake, growth, hepato-somatic index, apparent availability coefficient (AAC) of Fe, Cu, Mn and Zn and also lower whole body Se and Zn concentration, whereas whole body Fe and Cu and plasma Fe concentrations were higher. Feeding the V diet increased intestinal ferric reductase activity; at transcriptional level, hepatic hepcidin expression was down-regulated and ferroportin 1 was up-regulated. Transcription of intestinal Cu-transporting ATPases and hepatic copper transporter1 were higher in V0 compared to other groups. Among the hepatic metalo-enzyme activities assayed, only Se-dependent glutathione peroxidase was affected, being lower in V fed fish. Premix inclusion reduced the AAC of Fe, Cu and Zn; increased the whole body concentration of all micro- minerals; up-regulated hepatic hepcidin and down regulated intestinal ferroportin 1 transcription; and reduced the transcription of Cu-transporting ATPases in the intestine. Overall, the regulation of micro mineral metabolism in rainbow trout, especially Fe and Cu, was affected both by a change in ingredient composition and micro-mineral premix inclusion. PMID- 26895187 TI - Time resolution of the plastic scintillator strips with matrix photomultiplier readout for J-PET tomograph. AB - Recent tests of a single module of the Jagiellonian Positron Emission Tomography system (J-PET) consisting of 30 cm long plastic scintillator strips have proven its applicability for the detection of annihilation quanta (0.511 MeV) with a coincidence resolving time (CRT) of 0.266 ns. The achieved resolution is almost by a factor of two better with respect to the current TOF-PET detectors and it can still be improved since, as it is shown in this article, the intrinsic limit of time resolution for the determination of time of the interaction of 0.511 MeV gamma quanta in plastic scintillators is much lower. As the major point of the article, a method allowing to record timestamps of several photons, at two ends of the scintillator strip, by means of matrix of silicon photomultipliers (SiPM) is introduced. As a result of simulations, conducted with the number of SiPM varying from 4 to 42, it is shown that the improvement of timing resolution saturates with the growing number of photomultipliers, and that the [Formula: see text] configuration at two ends allowing to read twenty timestamps, constitutes an optimal solution. The conducted simulations accounted for the emission time distribution, photon transport and absorption inside the scintillator, as well as quantum efficiency and transit time spread of photosensors, and were checked based on the experimental results. Application of the [Formula: see text] matrix of SiPM allows for achieving the coincidence resolving time in positron emission tomography of [Formula: see text]0.170 ns for 15 cm axial field-of-view (AFOV) and [Formula: see text]0.365 ns for 100 cm AFOV. The results open perspectives for construction of a cost-effective TOF-PET scanner with significantly better TOF resolution and larger AFOV with respect to the current TOF-PET modalities. PMID- 26895189 TI - Human Factors and Quality Improvement in the Emergency Department: Reducing Potential Errors in Blood Collection. AB - OBJECTIVES: Adverse events in blood collection procedures such as mismatched or unlabeled samples may have critical implications on patient safety (such as wrong diagnosis and treatments). The current study examined blood collection procedures in an emergency department before and after the application of a human factors approach for improving performance quality and preventing adverse events. METHODS: In the emergency department of a community care hospital, 190 blood collection events were observed in 2 phases: preintervention and postintervention. Two quality measures were tested as follows: quality measure 1, performing all 7 stages in the procedure of blood collection according to protocol, and quality measure 2, performing the stages of the procedure in the correct sequence according to the protocol. In addition, medical staff anonymously answered questionnaires about their procedure for collecting blood. RESULTS: Analyses of data collected before the intervention revealed only 2 events in which all 7 stages in the protocol of the procedure were performed and only 1 event in which the 7 stages of the procedure were performed in the correct sequence. In 91% of the events, the patient was not fully identified. Based on these findings, we developed an intervention using a human factors approach to improve the quality of performance. Analyses of data collected after the intervention revealed significant differences (t188 = -14.9, rho < 0.01) in quality measure 1 before (mean [SD], 4.8 [0.6]) and after (mean [SD], 6.4 [0.8]) the intervention was initiated, which implies improvement on efficiency subsequent to the implementation of the intervention. Improvement also appeared in quality measure 2. CONCLUSIONS: This study illustrates the nature of potential errors in blood collection performance, offering a proactive approach to improve the rate of proper performance. PMID- 26895188 TI - Recently identified drug resistance biomarkers in ovarian cancer. AB - Ovarian cancer, consisting mainly of ovarian carcinoma, is the most lethal gynecologic malignancy. Improvements in outcome for patients with advanced-stage disease are limited by intrinsic and acquired chemoresistance and by tumor heterogeneity at different anatomic sites and along disease progression. Molecules and cellular pathways mediating chemoresistance appear to be different for the different histological types of ovarian carcinoma, with most recent research focusing on serous and clear cell carcinoma. This review discusses recent data implicating various biomarkers in chemoresistance in this cancer, with focus on studies in which clinical specimens have been central. PMID- 26895190 TI - Upper critical field, pressure-dependent superconductivity and electronic anisotropy of Sm4Fe2As2Te(1-x)O(4-y)F(y). AB - We present a detailed study of the electrical transport properties of a recently discovered iron-based superconductor: Sm4Fe2As2Te0.72O2.8F1.2. We followed the temperature dependence of the upper critical field by resistivity measurement of single crystals in magnetic fields up to 16 T, oriented along the two main crystallographic directions. This material exhibits a zero-temperature upper critical field of 90 T and 65 T parallel and perpendicular to the Fe2As2 planes, respectively. An unprecedented superconducting magnetic anisotropy gammaH=H(c2)(ab)/H(c2)(c) ~ 14 is observed near Tc, and it decreases at lower temperatures as expected in multiband superconductors. Direct measurement of the electronic anisotropy was performed on microfabricated samples, showing a value of rho(c)/rho(ab)(300K) ~ 5 that rises up to 19 near Tc . Finally, we have studied the pressure and temperature dependence of the in-plane resistivity. The critical temperature decreases linearly upon application of hydrostatic pressure (up to 2 GPa) similarly to overdoped cuprate superconductors. The resistivity shows saturation at high temperatures, suggesting that the material approaches the Mott-Ioffe-Regel limit for metallic conduction. Indeed, we have successfully modelled the resistivity in the normal state with a parallel resistor model that is widely accepted for this state. All the measured quantities suggest strong pressure dependence of the density of states. PMID- 26895192 TI - Right Ventricular Imaging in 25 Seconds: Evaluating the Use of Sparse Sampling CINE With Iterative Reconstruction for Volumetric Analysis of the Right Ventricle. AB - OBJECTIVE: The aim of this study was to prospectively evaluate a 2-dimensional real-time CINE TrueFISP magnetic resonance sequence using sparse data sampling with iterative reconstruction (SSIR) for right ventricular (RV) volumetry in comparison to the criterion standard (CS) acquired at 3 T. MATERIALS AND METHODS: Ten healthy controls and 20 consecutive patients scheduled for cardiac magnetic resonance imaging on a 3-T system (Magnetom Skyra; Siemens Healthcare Sector, Germany) underwent undersampled SSIR sequences with a single breath-hold (BH) as well as with shallow free breathing (NBH) and a fully sampled multi-BH sequence as CS. Right ventricular volumetry was performed with dedicated cardiac magnetic resonance software (cvi42; Circle Cardiovascular Imaging Inc, Calgary, Alberta, Canada). Agreement of SSIR with and without BH and CS for RV functional parameters (end-systolic volume [RVESV], end-diastolic volume [RVEDV], stroke volume [RVSV], and ejection fraction [RVEF]) were assessed with Bland-Altman analysis and paired t test. RESULTS: Analysis of the 30 individuals (19 male; 48 +/- 14 years) revealed no significant differences when comparing CS and BH measurements for RVEDV (153.7 vs 153.6 mL, P = 0.96), RVESV (71.6 vs 72.1 mL, P = 0.78), RVSV (82.0 vs 81.6 mL, P = 0.65), and RVEF (54.9% vs 54.2%, P = 0.19). Similar results were shown when comparing CS and NBH measurements for RVEDV (153.7 vs 152.2 mL, P = 0.34), RVESV (71.6 vs 72.8 mL, P = 0.30), RVSV (82.0 vs 81.0 mL, P = 0.46), and RVEF (54.9 vs 54.4, P = 0.48). Time taken for acquisition was 350 seconds for the CS, 34 seconds for BH, and 25 seconds for NBH measurements. Additional time required for iterative reconstruction was 2 minutes and 30 seconds for the sparse sampled data sets. CONCLUSIONS: Our results demonstrate that accurate RV volumetry with SSIR data at 3 T is feasible in clinical routine within 25 seconds even without BH, which is of particular importance in patients with dyspnea. PMID- 26895191 TI - Immunisation With Immunodominant Linear B Cell Epitopes Vaccine of Manganese Transport Protein C Confers Protection against Staphylococcus aureus Infection. AB - Vaccination strategies for Staphylococcus aureus, particularly methicillin resistant S. aureus (MRSA) infections have attracted much research attention. Recent efforts have been made to select manganese transport protein C, or manganese binding surface lipoprotein C (MntC), which is a metal ion associated with pathogen nutrition uptake, as potential candidates for an S. aureus vaccine. Although protective humoral immune responses to MntC are well-characterised, much less is known about detailed MntC-specific B cell epitope mapping and particularly epitope vaccines, which are less-time consuming and more convenient. In this study, we generated a recombinant protein rMntC which induced strong antibody response when used for immunisation with CFA/IFA adjuvant. On the basis of the results, linear B cell epitopes within MntC were finely mapped using a series of overlapping synthetic peptides. Further studies indicate that MntC113 136, MntC209-232, and MntC263-286 might be the original linear B-cell immune dominant epitope of MntC, furthermore, three-dimensional (3-d) crystal structure results indicate that the three immunodominant epitopes were displayed on the surface of the MntC antigen. On the basis of immunodominant MntC113-136, MntC209 232, and MntC263-286 peptides, the epitope vaccine for S. aureus induces a high antibody level which is biased to TH2 and provides effective immune protection and strong opsonophagocytic killing activity in vitro against MRSA infection. In summary, the study provides strong proof of the optimisation of MRSA B cell epitope vaccine designs and their use, which was based on the MntC antigen in the development of an MRSA vaccine. PMID- 26895193 TI - Initial Results of a Single-Source Dual-Energy Computed Tomography Technique Using a Split-Filter: Assessment of Image Quality, Radiation Dose, and Accuracy of Dual-Energy Applications in an In Vitro and In Vivo Study. AB - OBJECTIVE: The aim of this study was to investigate the image quality, radiation dose, and accuracy of virtual noncontrast images and iodine quantification of split-filter dual-energy computed tomography (CT) using a single x-ray source in a phantom and patient study. MATERIALS AND METHODS: In a phantom study, objective image quality and accuracy of iodine quantification were evaluated for the split filter dual-energy mode using a tin and gold filter. In a patient study, objective image quality and radiation dose were compared in thoracoabdominal CT of 50 patients between the standard single-energy and split-filter dual-energy mode. The radiation dose was estimated by size-specific dose estimate. To evaluate the accuracy of virtual noncontrast imaging, attenuation measurements in the liver, spleen, and muscle were compared between a true noncontrast premonitoring scan and the virtual noncontrast images of the dual-energy scans. Descriptive statistics and the Mann-Whitney U test were used. RESULTS: In the phantom study, differences between the real and measured iodine concentration ranged from 2.2% to 21.4%. In the patient study, the single-energy and dual energy protocols resulted in similar image noise (7.4 vs 7.1 HU, respectively; P = 0.43) and parenchymal contrast-to-noise ratio (CNR) values for the liver (29.2 vs 28.5, respectively; P = 0.88). However, the vascular CNR value for the single energy protocol was significantly higher than for the dual-energy protocol (10.0 vs 7.1, respectively; P = 0.006). The difference in the measured attenuation between the true and the virtual noncontrast images ranged from 3.1 to 6.7 HU. The size-specific dose estimate of the dual-energy protocol was, on average, 17% lower than that of the single-energy protocol (11.7 vs 9.7 mGy, respectively; P = 0.008). CONCLUSIONS: Split-filter dual-energy compared with single-energy CT results in similar objective image noise in addition to dual-energy capabilities at 17% lower radiation dose. Because of beam hardening, split-filter dual-energy can lead to decreased CNR values of iodinated structures. PMID- 26895194 TI - Diffusion Tensor Imaging of Lumbar Nerve Roots: Comparison Between Fast Readout Segmented and Selective-Excitation Acquisitions. AB - OBJECTIVES: The aim of this study was to compare the quality of recently emerged advanced diffusion tensor imaging (DTI) techniques with conventional single-shot echo-planar imaging (EPI) in a functional assessment of lumbar nerve roots. MATERIALS AND METHODS: The institutional review board approved the study including 12 healthy volunteers. Diffusion tensor imaging was performed at 3 T (MAGNETOM Skyra; Siemens Healthcare) with b-values of 0 and 700 s/mm and an isotropic spatial resolution for subsequent multiplanar reformatting. The nerve roots L2 to S1 were imaged in coronal orientation with readout-segmented EPI (rs DTI) and selective-excitation EPI (sTX-DTI) with an acquisition time of 5 minutes each, and in axial orientation with single-shot EPI (ss-DTI) with an acquisition time of 12 minutes (scan parameters as in recent literature). Two independent readers qualitatively and quantitatively assessed image quality. RESULTS: The interobserver reliability ranged from "substantial" to "almost perfect" for all examined parameter and all 3 sequences (kappa = 0.70-0.94). Overall image quality was rated higher, and artifact levels were scored lower for rs-DTI and sTX-DTI than for ss-DTI (P = 0.007-0.027), while fractional anisotropy and signal-to noise ratio values were similar for all sequences (P >= 0.306 and P >= 0.100, respectively). Contrast-to-noise ratios were significantly higher for rs-DTI and ss-DTI than for sTX-DTI (P = 0.004-0.013). CONCLUSIONS: Despite shorter acquisition times, rs-DTI and sTX-DTI produced images of higher quality with smaller geometrical distortions than the current standard of reference, ss-DTI. Thus, DTI acquisitions in the coronal plane, requiring fewer slices for full coverage of exiting nerve roots, may allow for functional neurography in scan times suitable for routine clinical practice. PMID- 26895195 TI - Single Breath-Hold T1rho-Mapping of the Heart for Endogenous Assessment of Myocardial Fibrosis. AB - OBJECTIVES: In this study, we propose a method to acquire high spatial-resolution T1rho-maps, which allows bright and black-blood imaging, in a single breath-hold. To validate this innovative method, the reproducibility was tested in phantoms and volunteers. Lastly, the sensitivity and specificity for infarct detection was compared with the criterion standard late gadolinium enhancement (LGE). METHODS: T1rho-mapping was performed using a T1rho-prepared balanced steady-state free precession sequence at 1.5 T and 3 T. Five images with increasing spin-lock preparation times (spin-lock = 0, 10, 20, 30, 40 milliseconds, amplitude = 500 Hz) were acquired with an interval of 3 beats. Black-blood imaging was performed using a double inversion pulse sequence. The method was tested in 2 times 10 healthy volunteers at 1.5 and 3 T and in 9 myocardial infarction patients at 1.5 T. T1rho-maps, and LGE images were scored for presence and extent of myocardial scarring. RESULTS: Phantom results show that the proposed T1rho-mapping method gives accurate T1rho-values. The mean T1rho-relaxation time of the myocardium in healthy controls was 52.8 +/- 1.8 milliseconds at 1.5 T and 46.4 +/- 1.8 milliseconds at 3 T. In patients, the T1rho of infarcted myocardium was (82.4 +/- 5.2 milliseconds), and the T1rho of remote myocardium was (54.2 +/- 2.8 milliseconds; P < 0.0001). Sensitivity of infarct detection on a T1rho-map was 70%, with a specificity of 94%, compared with LGE. CONCLUSIONS: In this study, we have investigated a method to acquire high spatial-resolution T1rho-maps of the heart in a single breath-hold. This method proved to be reproducible and had high specificity compared with LGE and can thus be used for the endogenous detection of myocardial fibrosis in patients with ischemic cardiomyopathy. PMID- 26895196 TI - Perfusion Assessment Using Intravoxel Incoherent Motion-Based Analysis of Diffusion-Weighted Magnetic Resonance Imaging: Validation Through Phantom Experiments. AB - OBJECTIVES: The aims of this study were to demonstrate the theoretical meaning of intravoxel incoherent motion (IVIM) parameters and to compare the robustness of 2 biexponential fitting methods through magnetic resonance experiments using IVIM phantoms. MATERIALS AND METHODS: Intravoxel incoherent motion imaging was performed on a 3 T magnetic resonance imaging scanner using 15 b values (0-800 s/mm) for 4 phantoms with different area fractions of the flowing water compartment (FWC%), at the infusion flow rates of 0, 1, 2, and 3 mL/min. Images were quantitatively analyzed using monoexponential free biexponential, and segmented biexponential fitting models. RESULTS: There were some inconsistent variations in Dslow with changing flow rates. The perfusion fraction, f, showed a significant positive correlation with the flow rate for both the free and segmented fitting methods (rho = 0.838 to 0.969; P < 0.001). The fast diffusion coefficient, Dfast, had a significant positive correlation with the flow rate for segmented fitting (rho = 0.745 to 0.969; P < 0.001), although it showed an inverse correlation with the flow rate for free fitting (rho = -0.527 to -0.791; P <= 0.017). Significant positive correlations with the FWC% of the phantoms were noted for f (P = 0.510 for free fitting and P = 0.545 for segmented fitting, P < 0.001). CONCLUSIONS: The IVIM model allows for an approximate segmentation of molecular diffusion and perfusion, with a minor contribution of the perfusion effect on Dslow. The f and Dfast can provide a rough estimation of the flow fraction and flow velocity. Segmented fitting may be a more robust method than free fitting for calculating the IVIM parameters, especially for Dfast. PMID- 26895199 TI - Bearing Witness to the Exit: Depriving Death of Its Strangeness. PMID- 26895198 TI - The Impact of Advance Directives on End-of-Life Care for Adolescents and Young Adults Undergoing Hematopoietic Stem Cell Transplant. AB - BACKGROUND: Little is known about the role of advance directives (AD) in end-of life (EOL) care for adolescents and young adults (AYA) undergoing hematopoietic stem cell transplant (HSCT). OBJECTIVE: The study objective was to describe the frequency, type, and influence of AD on the use of life-sustaining treatment (LST) in AYA patients undergoing HSCT. METHODS: We performed a retrospective chart review of 96 patients aged 14-26 undergoing HSCT between April 2011 and January 2015 at the University of Minnesota. LST was defined as the use of positive pressure ventilation (PPV), dialysis, or CPR. RESULTS: Of the 96 patients, survival was 72.9%, and 23% had an AD. Of the 26 patients who died, 13 (50%) had an AD. Among the 19 patients who died in the ICU, there was no significant difference in PPV, dialysis, withholding or withdrawing of LST, or timing of do not resuscitate (DNR) orders between those with ADs preferring LST (n = 5), those naming proxies only (n = 4), and those without ADs (n = 10). Patients with ADs expressing preference for LST were significantly more likely to receive CPR than those with proxies or those without ADs (p = 0.02). CONCLUSION: A minority of AYA patients undergoing HSCT had ADs. Patients received care that was strongly associated with their preferences. With the exception of CPR, the use of LST did not differ between those with ADs and those without. PMID- 26895201 TI - Two Scalable Syntheses of (S)-2-Methylazetidine. AB - Two orthogonal routes for preparing (S)-2-methylazetidine as a bench stable, crystalline (R)-(-)-CSA salt are presented. One route features the in situ generation and cyclization of a 1,3-bis-triflate to form the azetidine ring, while the second route involves chemoselective reduction of N-Boc azetidine-2 carboxylic acid. Both sequences afford the desired product in good overall yields (61% and 49%) and high enantiomeric excess (>99% ee), avoid column chromatography, and are suitable for the large-scale production of this material. PMID- 26895200 TI - The role of fortified foods and nutritional supplements in increasing vitamin D intake in Irish preschool children. AB - PURPOSE: There are limited data on the contribution of fortified foods and nutritional supplements to intakes of vitamin D in young children. Our objective was to examine the intake, adequacy, risk of excessive intake and sources of dietary vitamin D. METHODS: The nationally representative cross-sectional dietary survey of young children (aged 1-4 years) (n 500) was used to evaluate vitamin D intake and quantify the contribution of the base diet, fortified foods and nutritional supplements to total intake. RESULTS: Median (IQR) intakes of vitamin D were generally low in this young population, ranging from 2.0 (1.9) to 2.5 (4.9) ug/day. Ninety-three and 78 % of children had intakes below 10 and 5 ug/day, respectively. While vitamin D supplement users (17 %) had the highest intakes [6.7 (6.4) ug/day] (P < 0.001), 74 % had intakes below 10 ug/day. Vitamin D-fortified foods, consumed by 77 % of children [2.2 (2.0) ug/day], made nutritionally significant contributions to intake [0.8 (1.6) ug/day], particularly in younger children [1.5 (4.6) ug/day]. Children who did not use nutritional supplements or fortified foods had significantly (P < 0.001) lower intakes of vitamin D than the other groups [1.0 (0.8) ug/day]. Our analyses show the importance of milk and yoghurt, meat and fortified ready-to-eat cereals as sources of vitamin D in this age group. The use of nutritional supplements or fortified foods at current levels does not represent a risk of intakes exceeding the European Food Safety Authority (EFSA) tolerable upper intake level (UL) (50 ug/day), as intakes did not exceed or even approach the UL (P95: 22 % of UL). CONCLUSION: Intakes of vitamin D in preschool children in Ireland are generally low. Nutritional supplements and fortified foods make significant contributions to intakes of vitamin D, without risk of unacceptably high intakes. Though supplements are effective in raising intakes of vitamin D in users, uptake is low (17 %). Food fortification may represent a suitable public health approach to increasing vitamin D intakes. The national food consumption data of Irish preschool children provide the ideal starting point for modelling of fortification scenarios to identify which foods and levels of addition will ensure effective and safe increases in vitamin D intake. PMID- 26895202 TI - Approach for oligometastasis in non-small cell lung cancer. AB - Non-small cell lung cancer (NSCLC) harboring a limited number of distant metastases, referred to as the oligometastatic state, has been indicated for surgery for the past several decades. However, whether the strategy of surgical treatment results in a survival benefit for such patients remains controversial. Experientially, however, thoracic surgeons often encounter long-term survivors among surgically resected oligometastatic NSCLC patients. In this article, the current situation of surgical approach and potential future perspective for oligometastatic NSCLC are reviewed. PMID- 26895205 TI - Correction: A convenient domino Ferrier rearrangement-intramolecular cyclization for the synthesis of novel benzopyran-fused pyranoquinolines. AB - Correction for 'A convenient domino Ferrier rearrangement-intramolecular cyclization for the synthesis of novel benzopyran-fused pyranoquinolines' by Paseka T. Moshapo et al., Org. Biomol. Chem., 2016, DOI: 10.1039/c5ob02536b. PMID- 26895203 TI - Confirmatory Factor Analysis and Differential Relationships of the Two Subdomains of Negative Symptoms in Chronically Ill Psychotic Patients. AB - Research suggests a two factor structure for negative symptoms in patients with psychotic disorders: social amotivation (SA) and expressive deficits (ED). Applying this two-factor structure in clinical settings may provide valuable information with regard to outcomes and to target treatments. We aimed to investigate 1) whether the factor structure is also supported in chronically ill patients with a psychotic disorder and 2) what the relationship is between these factors and functioning (overall functioning and living situation), depressive symptoms and quality of life. 1157 Patients with a psychotic disorder and a duration of illness of 5 years or more were included in the analysis (data selected from the Pharmacotherapy Monitoring Outcome Survey; PHAMOUS). A confirmatory factor analysis was performed using items of the Positive and Negative Syndrome Scale that were previously identified to reflect negative symptoms (N1-4, N6, G5, G7, G13, G16). Subsequently, regression analysis was performed on outcomes. The results confirmed the distinction between SA (N2, N4, G16) and ED (N1, N3, N6, G5, G7, G13) in chronically ill patients. Both factors were related to worse overall functioning as measured with the Health of the Nation Outcome Scales, ED was uniquely associated with residential living status. Higher scores for SA were associated with more depressive symptoms and worse quality of life. Thus, SA is most strongly related to level of social-emotional functioning, while ED are more related to living situation and thereby are indicative of level of everyday functioning. This subdivision may be useful for research purposes and be a valuable additional tool in clinical practice and treatment development. PMID- 26895204 TI - Development of rAAV2-CFTR: History of the First rAAV Vector Product to be Used in Humans. AB - The first human gene therapy trials using recombinant adeno-associated virus (rAAV) vectors were performed in cystic fibrosis (CF) patients. Over 100 CF patients were enrolled in 5 separate trials of rAAV2-CFTR administration via nasal, endobronchial, maxillary sinus, and aerosol delivery. Recombinant AAV vectors were designed to deliver the CF transmembrane regulator (CFTR) gene and correct the basic CFTR defect by restoring chloride transport and reverting the upregulation of proinflammatory cytokines. However, vector DNA expression was limited in duration because of the low incidence of integration and natural airway epithelium turnover. In addition, repeated administration of AAV-CFTR vector resulted in a humoral immune response that prevented effective gene transfer from subsequent doses of vector. AAV serotype 2 was used in human trials before the comparison with other serotypes and determination that serotypes 1 and 5 not only possess higher tropism for the airway epithelium, but also are capable of bypassing the binding and trafficking processes-both were important hindrances to the effectiveness of rAAV2. Although rAAV-CFTR gene therapy does not appear likely to supplant newer small-molecule CFTR modulators in the near future, early work with rAAV-CFTR provided an important foundation for later use of rAAV in humans. PMID- 26895206 TI - Microelectrode recording (MER) findings during sleep-awake anesthesia using dexmedetomidine in deep brain stimulation surgery for Parkinson's disease. AB - OBJECTIVE: The preferred choice of anesthesia for deep brain stimulation (DBS) has been local anesthesia due to the need of patients' cooperation during the procedure, and concern on the interference of sedatives on microelectrode recording (MER) results. However, local anesthesia during the whole procedure may be impossible in some patients due to uncontrolled anxiety, fear, delirium or exhaustion. Therefore, sedative drugs have been used for DBS, but findings of MER during the procedures have not been reported in detail, especially in the globus pallidus internus (GPi). We introduce our experience using 'asleep-awake' technique by dexmedetomidine (DEX) anesthesia with MER findings during DBS in idiopathic Parkinson's disease (IPD) patients. PATIENTS AND METHODS: Data from 14 different subcortical nuclei from 8 consecutive IPD patients whom had DBS at the GPi (6 patients) and subthalamic nucleus (STN) (2 patients) were retrospectively reviewed. We used continuous DEX and intermittent small boluses of propofol during the painful procedure ('asleep phase'), accompanied with continuous intraoperative monitorings of bispectral index (BIS) and modified observer's assessment of sedation (MOAA/S). Then sedatives were discontinued during MER recording ('awake phase'). Characteristic findings and firing rates of neurons were analyzed and compared to those from other 6 patients who underwent surgery under local anesthesia. RESULTS: All patients were satisfactorily sedated using this technique without any respiratory or hemodynamic complications. Characteristics of spike activities of each nucleus were inspected and analyzed quantitatively. We could inspect changes of spike activities according to level of patients' consciousness in some cases, but the localizing value was good to decide the target in all cases. Firing rates of group whom sedatives were given during asleep phase ('sedatives') were significantly lower than those of group under local anesthesia ('no sedative'). Intraoperative length of target nuclei, postoperative imaging and postoperative changes of UPDRS III score indicated satisfactory outcome. CONCLUSION: We concluded that though MER findings may change during DEX-based monitored 'sleep-awake' anesthesia, it did not affect the results of target localization for the clinical purpose. However, it should be considered that use of sedatives before MER could result in changes of firing rate and pattern depending on the patient's state of consciousness. PMID- 26895207 TI - Clinical outcomes after ventriculoatrial shunting for idiopathic normal pressure hydrocephalus. AB - INTRODUCTION: Idiopathic normal pressure hydrocephalus (iNPH) is a neurological disorder that classically presents with a triad of progressive gait impairment, urinary incontinence, and cognitive deterioration. Treatment predominantly involves ventriculoperitoneal (VP) shunting, but one alternative is ventriculoatrial (VA) shunting. This study sought to describe and evaluate the clinical outcomes of patients with iNPH primarily treated with VA shunting. MATERIALS AND METHODS: A retrospective review of patients with iNPH who were treated with VA shunting at a single institution, from 2003 to 2013, was performed. RESULTS: 58 patients with iNPH underwent primary VA shunting at a median age of 74 (IQR: 70-80) years. The most common comorbidities included hypertension (n=39, 67%) and diabetes mellitus (n=11, 19%). Median duration of symptoms prior to VA shunting was 24 (IQR: 12-36) months. All patients had gait impairment, 52 (90%) had cognitive decline, and 43 (74%) had urinary incontinence. Forty-three (74%) patients had all three symptoms. At a median last follow-up of 16 (IQR: 7-26) months, median iNPH score improved from 6 to 3 (p<0.0001), mini mental status exam (MMSE) tended to increase from 26 to 29 (p=0.082), timed up-and-go (TUG) improved from 18 to 13s (p<0.0001), and Tinetti score improved from 19 to 25 (p<0.0001) after VA shunting. 78% of patients had improvement in at least one of their symptoms with 66% of patients having improvement in gait, 53% having improvement in their cognition, and 52% having improved urinary incontinence. A total of 21 patients (36%) had improvement in all 3 symptoms. CONCLUSIONS: There were significant improvements in functional outcomes as evaluated via the iNPH score, TUG, and Tinetti score, while improvement in MMSE trended toward significance. Patients also had improvement of clinical symptoms related to gait, urinary function and cognition. These results suggest that VA shunting can be an effective primary treatment alternative to VP shunting for iNPH. PMID- 26895208 TI - The use of the YELLOW 560 nm surgical microscope filter for sodium fluorescein guided resection of brain tumors: Our preliminary results in a series of 28 patients. AB - OBJECTIVE: Sodium fluorescein (Na-Fl) is a fluorescent dye that accumulates in tumoral tissues via disrupted blood-brain barrier. It has been used in fluorescence-guided surgery for various brain tumors. Herein, we report our initial experience and preliminary results for the first 28 patients who were operated on under Na-Fl guidance with the use of a special filter on the surgical microscope. PATIENT AND METHODS: Between January and November 2015, 200 mg (2-4 mg/kg) of Na-Fl was administered in 28 patients (30 surgeries) after anesthesia induction. The clinical features, surgical observations, extent of resection on the postoperative magnetic resonance imaging (MRI) and histopathology of the tumors were retrospectively analyzed. The use of YELLOW 560 nm filter was found "helpful" if the discrimination of the pinkish brain tissue and bright yellow stained tumor tissue was clear. Otherwise, it was described as "not helpful. RESULTS: There were 23 high-grade and 7 metastatic tumors in our study group. Na Fl was found helpful by means of the tumor demarcation in 29 of 30 operations (97%). In 23 of these 29 operations (79%), a total resection was achieved regardless of the tumor pathology. No adverse events were encountered regarding the use of Na-Fl. CONCLUSION: Na-Fl guidance with the use of a YELLOW 560 filter is safe and effective in high-grade glioma and metastatic tumor surgery. We think it is feasible for increasing the extent of resection in these tumors. PMID- 26895209 TI - Increased apoptosis in the platelets of patients with Alzheimer's disease and amnestic mild cognitive impairment. AB - OBJECTIVES: Alzheimer's disease (AD), the most common cause of dementia, is a progressive, incurable neurodegenerative disorder. Platelet is a suitable source of human peripheral tissue to study pathological mechanisms occurring in the brain. The present study aims to investigate (1) whether abnormal apoptotic events besides involved in AD within the central neurologic system, could also occur at peripheral platelet level; (2) whether apoptosis at peripheral platelet level starts at the early stage of AD. PATIENTS AND METHODS: Amnestic mild cognitive impairment (MCI), AD, and age-matched healthy individuals were recruited, and each group had 50 person. In the present study, we investigate whether alterations of caspase family and Bcl2 family could be found in the platelets in Alzheimer's disease (AD) and amnestic mild cognitive impairment (MCI) patients. The platelet levels of caspase protein and Bcl2 family were analyzed by western blot. RESULTS: The results show that the platelet levels of caspase-3, caspase-9, Bad, and Bax significantly increased in AD and amnestic MCI. The increased apoptosis proteins levels in amnestic MCI were found between AD and normal controls. The anti-apoptosis protein Bcl2 increased in amnestic MCI, while decreased in AD. CONCLUSION: We suggest that increased apoptosis exist in the platelet and might mirror apoptosis within the brain. Abnormal apoptosis may appear in the early of AD, and the ratio between pro- and anti-apoptotic protein levels partially determines the susceptibility of platelet to a death signal. In conclusion, platelet may be a good model to study apoptotic pathways of AD. PMID- 26895210 TI - Bronchial Paraganglioma with SDHB Deficiency. AB - Though most paragangliomas arise as sporadic tumors, the recent advantages in the genetic screening revealed that about 30 % of paragangliomas are linked to hereditary mutations, such as those involving SDH genes. A 22-year-old woman carrying a left main bronchus tumor underwent surgery in our institution. Her past medical history included a GIST without KIT or PDGFRA mutation. The histological examination revealed a nested proliferation of medium-sized cells expressing neuroendocrine markers (chromogranin A and synaptophysin). The neoplastic cells failed to express SDHB gene product. These findings led us to the final diagnosis of bronchial paraganglioma in the setting of Carney-Stratakis syndrome. Bronchial paragangliomas are exceedingly rare tumors with polymorphous clinical presentation, and usually benign clinical course. Though most paragangliomas are sporadic, some tumors are associated with specific hereditary disease, especially those occurring in young patients or in combination with other neoplasms. PMID- 26895211 TI - Nanoscale Distribution of Sulfonic Acid Groups Determines Structure and Binding of Water in Nafion Membranes. AB - The connection between the nanoscale structure of two chemically equivalent, yet morphologically distinct Nafion fuel-cell membranes and their macroscopic chemical properties is demonstrated. Quantification of the chemical interactions between water and Nafion reveals that extruded membranes have smaller water channels with a reduced sulfonic acid head group density compared to dispersion cast membranes. As a result, a disproportionally large amount of non-bulk water molecules exists in extruded membranes, which also exhibit larger proton conductivity and larger water mobility compared to cast membranes. The differences in the physicochemical properties of the membranes, that is, the chemical constitution of the water channels and the local water structure, and the accompanying differences in macroscopic water and proton transport suggest that the chemistry of nanoscale channels is an important, yet largely overlooked parameter that influences the functionality of fuel-cell membranes. PMID- 26895213 TI - Thromboelastographic predictors of venous thromboembolic events in critically ill patients: are we missing something? AB - Deep venous thromboembolism and pulmonary embolism are still underdiagnosed in the ICU. Thromboelastography (TEG) has shown considerable variability in sensitivity and specificity as a predictor of venous thromboembolism (VTE). We designed a prospective double-blind observational study to predict the risk of VTE using TEG in a cohort of critically ill patients. Seventy-two hours after admission in the ICU and consequent prophylaxis with low-molecular-weight heparin, we performed compressive color-Doppler ultrasound and diagnosed deep venous thrombosis. Computed tomography scan was performed for the diagnosis of pulmonary embolism if pulmonary embolism was suspected based on physical examination and transthoracic echocardiography. Whole blood samples were obtained from central venous lines 6-8 h after subcutaneous administration of low molecular-weight heparin. Native TEG and modified heparinase TEG were performed using a Thromboelastograph Coagulation Analyzer. Fifty-seven patients were consecutively enrolled of which six (10.5%) developed deep venous thrombosis; two (3.5%) also developed pulmonary embolism. The native thrombodynamic ratio (TDR) was an independent predictor of the odds of thrombosis (odds ratio 1.016, P < 0.05, 95% confidence interval 1.008-1.047), with a 0.93 area under the ROC curve. Using 10.6 as the lower cut-off point, TDR showed 100% sensitivity and 0 negative likelihood ratio (95% confidence interval 0-0.4) in excluding the clinical diagnosis of VTE. Our results show that TDR predicts VTE in the ICU. Our findings are in agreement with those reported by other investigators, who demonstrated that a TDR less that 10 is associated with prophylactic levels of anti-Xa. PMID- 26895212 TI - Complex coordinated extracellular metabolism: Acid phosphatases activate diluted human leukocyte proteins to generate energy flow as NADPH from purine nucleotide ribose. AB - Complex metabolism is thought to occur exclusively in the crowded intracellular environment. Here we report that diluted enzymes from lysed human leukocytes produce extracellular energy. Our findings involve two pathways: the purine nucleotide catabolic pathway and the pentose phosphate pathway, which function together to generate energy as NADPH. Glucose6P fuel for NADPH production is generated from structural ribose of purine ribonucleoside monophosphates, ADP, and ADP-ribose. NADPH drives glutathione reductase to reduce an oxidized glutathione disulfide-glutathione redox couple. Acid phosphatases initiate ribose5P salvage from purine ribonucleoside monophosphates, and transaldolase controls the direction of carbon chain flow through the nonoxidative branch of the pentose phosphate pathway. These metabolic control points are regulated by pH. Biologically, this energy conserving metabolism could function in perturbed extracellular spaces. PMID- 26895214 TI - Antioxidant therapy improves non-thyroidal illness syndrome in uremic rats. AB - BACKGROUND: The roles of antioxidant therapy on non-thyroidal illness syndrome (NTIS) in uremic rats is still unclear. MATERIALS AND METHODS: Twenty-four Sprague-Dawley (SD) rats were randomly divided into blank, 5/6 nephrectomy (Nx), pyrrolidine dithiocarbamate (PDTC, 10 mg/100 g), sodium bicarbonate (SB, 0.1 g/100 g), N-acetylcysteine (NAC, 80 mg/100 g) and thyroid hormones (TH, levothyroxine 2 MUg/100 g) groups. The serum levels of malondialdehyde (MDA), superoxide dismutase (SOD), advanced oxidation protein products (AOPP), interleukin (IL)-1beta, free triiodothyronine (FT3), and thyroid stimulating hormone (TSH) were detected in the sixth week. The expressions of IL-1beta and deiodinase type 1 (DIO1) were assessed by western blotting. The nuclear factor kappa B (NF-kappaB) inflammatory signal pathway was confirmed by electrophoretic mobility shift assay (EMSA). RESULTS: Compared with 5/6 Nx group, PDTC and NAC significantly reduced the levels (p < 0.01, respectively) of serum MDA, AOPP, TSH, and elevated levels of serum SOD (p < 0.01, respectively) and FT3 (p = 0.016 and p < 0.01). Neither had significant effects on serum IL-1beta content (p = 0.612 and p = 0.582). PDTC and NAC markedly decreased the protein expression of IL-1beta (p < 0.01) and increased the protein expression of DIO1 (p < 0.01), respectively. Both had been considerably blunted NF-kappaB activity (p < 0.01). CONCLUSIONS: In uremic rat model, PDTC and NAC can effectively improve oxidative stress level and NTIS. In terms of improving oxidative stress level, NAC is probably superior to PDTC. PMID- 26895215 TI - Effect of mucosal healing (Mayo 0) on clinical relapse in patients with ulcerative colitis in clinical remission. AB - OBJECTIVE: The aim of this study was to identify the effect of mucosal healing (MH) on clinical relapse in patients with ulcerative colitis (UC) who are in clinical remission, with special reference to Mayo endoscopic subscore 0. METHODS: Between November 2005 and December 2013, medical records from a total of 215 patients with UC who underwent colonoscopic examination at the time of clinical remission were retrospectively reviewed. Endoscopic MH was defined as a '0 point' of Mayo endoscopic subscore (Mayo 0). Patients were categorized into two groups according to Mayo endoscopic subscore and then analyzed. RESULTS: The baseline characteristics of both groups (MH vs. no-MH), including age at diagnosis, gender, and initial clinical and colonoscopic findings, were not significantly different. The median follow-up duration was 80 (12-118) months. Factors predictive of longer clinical remission duration were age >=30 years at diagnosis (>=30 years vs. <30 years; hazard ratio [HR] 3.16, 95% CI 1.88-5.30, p < 0.001), shorter interval between diagnosis and clinical remission (<15 months vs. >=15 months; HR 1.93, 95% CI 1.13-3.28, p = 0.015), and presence of MH at clinical remission (HR 1.95, 95% CI 1.15-3.32, p = 0.014). With a Cox regression model, patients with MH at clinical remission were more likely to have longer duration of clinical remission than patients without MH. CONCLUSION: The achievement of MH, Mayo 0 in particular, in patients with UC who are in clinical remission is important in predicting a favorable disease course prognosis. PMID- 26895216 TI - Immune Complex-Type Deposits in the Fischer-344 to Lewis Rat Model of Renal Transplantation and a Subset of Human Transplant Glomerulopathy. AB - BACKGROUND: Antibody-mediated rejection is a leading cause for renal transplant loss. Rodent models are useful to dissect pathomechanisms and to develop treatment strategies. Although used for decades as a model, glomerular histopathological findings of Fischer-344 kidneys transplanted into Lewis rats have never been comprehensively described. METHODS: Kidneys from Fischer-344 rats were transplanted into Lewis rats as life-sustaining allografts without immunosuppression. Lewis isografts and normal Fischer-344 kidneys served as controls. Grafts were harvested at 9 days, 6 and 26 weeks. Histopathological examination included light microscopy, immunohistochemistry, and morphometry. Findings were compared with 51 human biopsies with transplant glomerulopathy. RESULTS: Most glomerular findings in rat allografts resembled human acute and chronic antibody-mediated rejection with glomerulitis, microthrombosis, microaneurysms, glomerular hypertrophy, podocyte loss, glomerular basement membrane splitting, and secondary focal and segmental glomerulosclerosis. In line with previous reports on nonendothelial antigens, glomerular immunoglobulin and C4d deposition was mostly nonendothelial. Only in 26-week allografts, we found mesangial and subendothelial immune complex-type electron-dense deposits. Similar deposits were found in 8 of 51 human biopsies with transplant glomerulopathy after rigorous exclusion of immune complexes of other cause, particularly recurrent glomerulonephritis and hepatitis C. CONCLUSIONS: Thus, our model closely reflects the glomerular changes of acute antibody-mediated rejection in humans and of a special subset of human transplant glomerulopathy. The significance of alloimmune immune complex-type deposits in human transplants deserves further investigation. PMID- 26895217 TI - The Noninvasive Urinary Polyomavirus Haufen Test Predicts BK Virus Nephropathy in Children After Hematopoietic Cell Transplantation: A Pilot Study. AB - BACKGROUND: After hematopoietic cell transplantation (HCT), polyoma-BK virus is associated with hemorrhagic cystitis and also with polyomavirus nephropathy (PVN). However, the true burden of post-HCT PVN is unknown because kidney biopsies are avoided due to their bleeding risk. The novel, noninvasive urinary PV-Haufen test detects PVN in kidney transplant recipients with greater than 95% positive/negative predictive values. We hypothesized that the detection of PV Haufen in voided urine samples-a positive PV-Haufen test-was also clinically significant after HCT. METHODS: We examined 21 suitable urine samples from 14 patients (median age, 15 years; 71.4% male) who were selected from repositories for having varying degrees of BK viremia (range, 0-1.0 * 10 copies/mL), hemorrhagic cystitis (present/absent), and data on kidney function. Urine samples were obtained at a median of 88 days post-HCT. RESULTS: The PV-Haufen were detected in 5 of 14 patients (35.7%) and 7 of 21 (33.3%) urine samples, with histologic confirmation of PVN in 1 autopsy specimen. After a median of 285 days post-HCT, patients with PV-Haufen had an increased risk of dialysis-dependent renal failure (P < 0.05). All 3 dialysis-dependent patients had PV-Haufen and died. The presence of urinary PV-Haufen was not significantly correlated with hemorrhagic cystitis. From the 16 urines collected during BK viremia, 43.8% were PV-Haufen-positive, and 56.2% were negative. The PV-Haufen were not present in the 5 urines from patients without concomitant BK-viremia. CONCLUSIONS: In this proof-of-concept study, a positive PV-Haufen test was only seen in some patients with BK viremia and was not associated with hemorrhagic cystitis. The detection of PV-Haufen suggests underlying PVN with an increased risk of kidney failure and dialysis. PMID- 26895219 TI - Recurrent IgA Nephropathy After Kidney Transplantation. AB - Large numbers of patients with end-stage kidney disease caused by IgA nephropathy are transplanted every year, and each of these patients faces the risk of recurrence in their kidney graft. We review the epidemiology, diagnosis, and outcomes of recurrent IgA nephropathy. Mechanistic insights, therapeutic options, and knowledge gaps are reviewed, and we discuss future options to better understand and manage this disorder. PMID- 26895218 TI - Ambulatory Blood Pressure, Left Ventricular Hypertrophy, and Allograft Function in Children and Young Adults After Kidney Transplantation. AB - BACKGROUND: Hypertension is a common complication and is an important risk factor for graft loss and adverse cardiovascular outcomes in pediatric kidney transplantation. Ambulatory blood pressure monitoring (ABPM) is the preferred method to characterize blood pressure status. METHODS: We conducted a retrospective review of a large cohort of children and young adults with kidney transplant to estimate the prevalence of abnormal ambulatory blood pressure (ABP), assess factors associated with abnormal ABP, and examine whether ambulatory hypertension is associated with worse allograft function and left ventricular hypertrophy (LVH). RESULTS: Two hundred twenty-one patients had ABPM, and 142 patients had echocardiographic results available for analysis. One third of the patients had masked hypertension, 32% had LVH, and 38% had estimated glomerular filtration rate less than 60 mL/min per 1.73 m. African-American race/Hispanic ethnicity and requirement for more than 1 antihypertensive medication were independently associated with having masked hypertension. In a multivariate analysis, abnormal blood pressure (masked or sustained hypertension combined) was an independent predictor for LVH among patients not receiving antihypertensive treatment (P = 0.025). In a separate analysis, the use of antihypertensive medications was independently associated with worse allograft function (P = 0.002) although abnormal blood pressure was not a significant predictor. CONCLUSIONS: In young kidney transplant recipients, elevated ABP is frequently unrecognized and undertreated. The high prevalence of abnormal ABP, including masked hypertension, and its association with LVH supports the case for routine ABPM and cardiac structure evaluation as the standard of care in these patients. PMID- 26895220 TI - Auger and Carrier Trapping Dynamics in Core/Shell Quantum Dots Having Sharp and Alloyed Interfaces. AB - The role of interface sharpness in controlling the excited state dynamics in CdSe/ZnSe core/shell particles is examined here. Particles composed of CdSe/ZnSe with 2.4-4.0 nm diameter cores and approximately 4 monolayer shells are synthesized at relatively low temperature, ensuring a sharp core-shell interface. Subsequent annealing results in cadmium and zinc interdiffusion, softening the interface. TEM imaging and absorption spectra reveal that annealing results in no change in the particle sizes. Annealing results in a 5-10 nm blue shift in the absorption spectrum, which is compared to calculated spectral shifts to characterize the extent of metal interdiffusion. The one- and two-photon dynamics are measured using time-resolved absorption spectroscopy. We find that biexcitons undergo biexponential decays, with fast and slow decay times differing by about an order of magnitude. The relative magnitudes of the fast and slow components depend on the sharpness of the core-shell interface, with larger fast component amplitudes associated with a sharp core-shell interface. The slow component is assigned to Auger recombination of band edge carriers and the fast decay component to Auger recombination of holes that are trapped in defects produced by lattice strain. Annealing of these particles softens the core-shell interface and thereby reduces the amount of lattice strain and diminishes the magnitude of the fast decay component. The time constant of the slow biexciton Auger recombination component changes only slightly upon softening of the core-shell interface. PMID- 26895221 TI - Mutagenicity and Pollutant Emission Factors of Solid-Fuel Cookstoves: Comparison with Other Combustion Sources. AB - BACKGROUND: Emissions from solid fuels used for cooking cause ~4 million premature deaths per year. Advanced solid-fuel cookstoves are a potential solution, but they should be assessed by appropriate performance indicators, including biological effects. OBJECTIVE: We evaluated two categories of solid fuel cookstoves for eight pollutant and four mutagenicity emission factors, correlated the mutagenicity emission factors, and compared them to those of other combustion emissions. METHODS: We burned red oak in a 3-stone fire (TSF), a natural-draft stove (NDS), and a forced-draft stove (FDS), and we combusted propane as a liquified petroleum gas control fuel. We determined emission factors based on useful energy (megajoules delivered, MJd) for carbon monoxide, nitrogen oxides (NOx), black carbon, methane, total hydrocarbons, 32 polycyclic aromatic hydrocarbons, PM2.5, levoglucosan (a wood-smoke marker), and mutagenicity in Salmonella. RESULTS: With the exception of NOx, the emission factors per MJd were highly correlated (r >= 0.97); the correlation for NOx with the other emission factors was 0.58-0.76. Excluding NOx, the NDS and FDS reduced the emission factors an average of 68 and 92%, respectively, relative to the TSF. Nevertheless, the mutagenicity emission factor based on fuel energy used (MJthermal) for the most efficient stove (FDS) was between those of a large diesel bus engine and a small diesel generator. CONCLUSIONS: Both mutagenicity and pollutant emission factors may be informative for characterizing cookstove performance. However, mutagenicity emission factors may be especially useful for characterizing potential health effects and should be evaluated in relation to health outcomes in future research. An FDS operated as intended by the manufacturer is safer than a TSF, but without adequate ventilation, it will still result in poor indoor air quality. CITATION: Mutlu E, Warren SH, Ebersviller SM, Kooter IM, Schmid JE, Dye JA, Linak WP, Gilmour MI, Jetter JJ, Higuchi M, DeMarini DM. 2016. Mutagenicity and pollutant emission factors of solid-fuel cookstoves: comparison with other combustion sources. Environ Health Perspect 124:974-982; http://dx.doi.org/10.1289/ehp.1509852. PMID- 26895222 TI - Sequence-Dependent Fluorescence of Cy3- and Cy5-Labeled Double-Stranded DNA. AB - The fluorescent intensity of Cy3 and Cy5 dyes is strongly dependent on the nucleobase sequence of the labeled oligonucleotides. Sequence-dependent fluorescence may significantly influence the data obtained from many common experimental methods based on fluorescence detection of nucleic acids, such as sequencing, PCR, FRET, and FISH. To quantify sequence dependent fluorescence, we have measured the fluorescence intensity of Cy3 and Cy5 bound to the 5' end of all 1024 possible double-stranded DNA 5mers. The fluorescence intensity was also determined for these dyes bound to the 5' end of fixed-sequence double-stranded DNA with a variable sequence 3' overhang adjacent to the dye. The labeled DNA oligonucleotides were made using light-directed, in situ microarray synthesis. The results indicate that the fluorescence intensity of both dyes is sensitive to all five bases or base pairs, that the sequence dependence is stronger for double (vs single-) stranded DNA, and that the dyes are sensitive to both the adjacent dsDNA sequence and the 3'-ssDNA overhang. Purine-rich sequences result in higher fluorescence. The results can be used to estimate measurement error in experiments with fluorescent-labeled DNA, as well as to optimize the fluorescent signal by considering the nucleobase environment of the labeling cyanine dye. PMID- 26895223 TI - Pregnancy outcomes after prenatal exposure to echinacea: the Norwegian Mother and Child Cohort Study. AB - INTRODUCTION: Previous studies have shown that echinacea is among the most widely used herbal medicines during pregnancy in Western countries. Despite its frequent use, we know little about the safety of this herbal medicine during pregnancy. The primary aim of this study was to study the consequences of the use of echinacea on malformations and common adverse pregnancy outcomes. Secondly, we aimed to characterize women using this herb in pregnancy. METHOD: This study is based on the Norwegian Mother and Child Cohort Study (MoBa) and included 68,522 women and their children. Information was retrieved from three self-administered questionnaires completed by the women in pregnancy weeks 17 and 30 and 6 months after birth. Information on pregnancy outcomes was retrieved from the Medical Birth Registry of Norway. Generalized estimating equations analyses were performed to assess the association between exposure to echinacea and pregnancy outcomes. Pearson's chi-square test was used to assess factors related to use of echinacea in pregnancy. RESULTS: Among 68,522 women, 363 (0.5 %) reported the use of echinacea during pregnancy. These women were characterized by high age and delivery before 2002 and were to a less extent smoking in pregnancy. The use of echinacea was not associated with an increased risk of malformations or adverse pregnancy outcomes. CONCLUSION: This study revealed no increased risk of malformations or adverse pregnancy outcomes after the use of echinacea in pregnancy. Studies on the safety of commonly used herbal medications are important to identify herbals that should be avoided in pregnancy. PMID- 26895225 TI - Maritime Transportation Risk Assessment of Tianjin Port with Bayesian Belief Networks. AB - This article develops a Bayesian belief network model for the prediction of accident consequences in the Tianjin port. The study starts with a statistical analysis of historical accident data of six years from 2008 to 2013. Then a Bayesian belief network is constructed to express the dependencies between the indicator variables and accident consequences. The statistics and expert knowledge are synthesized in the Bayesian belief network model to obtain the probability distribution of the consequences. By a sensitivity analysis, several indicator variables that have influence on the consequences are identified, including navigational area, ship type and time of the day. The results indicate that the consequences are most sensitive to the position where the accidents occurred, followed by time of day and ship length. The results also reflect that the navigational risk of the Tianjin port is at the acceptable level, despite that there is more room of improvement. These results can be used by the Maritime Safety Administration to take effective measures to enhance maritime safety in the Tianjin port. PMID- 26895224 TI - Investigating the specific core genetic-and-epigenetic networks of cellular mechanisms involved in human aging in peripheral blood mononuclear cells. AB - Aging is an inevitable part of life for humans, and slowing down the aging process has become a main focus of human endeavor. Here, we applied a systems biology approach to construct protein-protein interaction networks, gene regulatory networks, and epigenetic networks, i.e. genetic and epigenetic networks (GENs), of elderly individuals and young controls. We then compared these GENs to extract aging mechanisms using microarray data in peripheral blood mononuclear cells, microRNA (miRNA) data, and database mining. The core GENs of elderly individuals and young controls were obtained by applying principal network projection to GENs based on Principal Component Analysis. By comparing the core networks, we identified that to overcome the accumulated mutation of genes in the aging process the transcription factor JUN can be activated by stress signals, including the MAPK signaling, T-cell receptor signaling, and neurotrophin signaling pathways through DNA methylation of BTG3, G0S2, and AP2B1 and the regulations of mir-223 let-7d, and mir-130a. We also address the aging mechanisms in old men and women. Furthermore, we proposed that drugs designed to target these DNA methylated genes or miRNAs may delay aging. A multiple drug combination comprising phenylalanine, cholesterol, and palbociclib was finally designed for delaying the aging process. PMID- 26895226 TI - Early Guillain-Barre Syndrome associated with acute dengue fever. AB - Various forms of neurological manifestations are reported in dengue fever. We describe here three cases of concomitant Guillain-Barre syndrome and dengue virus (DENV) infection during the largest DENV-1 outbreak in New Caledonia. Research of viral RNA was positive in both blood and CSF samples. All patients were treated with intravenous polyvalent immunoglobulins and recovered without sequelae within one week. PMID- 26895227 TI - Management of mother-to-child transmission of hepatitis B virus: Propositions and challenges. AB - Chronic hepatitis B virus (HBV) infection due to mother-to-child transmission (MTCT) during perinatal period remains an important global health problem. Despite standard passive-active immunoprophylaxis with hepatitis B immunoglobulin (HBIG) and hepatitis B vaccine in neonates, up to 9% of newborns still acquire HBV infection, especially these from hepatitis B e antigen (HBeAg) positive mothers. Management of HBV infection in pregnancy still need to draw careful attention because of some controversial aspects, including the failure of passive active immunoprophylaxis in a fraction of newborns, the effect and necessity of periodical hepatitis B immunoglobulin (HBIG) injection to the mothers, the safety of antiviral prophylaxis with nucleoside/nucleotide analogs, the benefit of different delivery ways, and the safety of breastfeeding. In this review, we highlight these unsettled issues of preventive strategies in perinatal period, and we further aim to provide an optimal approach to the management of preventing MTCT of HBV infection. PMID- 26895229 TI - Rational Design of Si/SiO2 @Hierarchical Porous Carbon Spheres as Efficient Polysulfide Reservoirs for High-Performance Li-S Battery. AB - Integrated design of Si/SiO2 @hierar-chical porous carbon spheres is made and used as efficient polysulfide reservoir for enhancing lithium-sulfur battery (LSB) in terms of capacity, rate ability, and cycling stability via combined chemical and physical effects. PMID- 26895228 TI - Effect of artemether-lumefantrine (Coartem) on cytomegalovirus urine viral load during and following treatment for malaria in children. AB - BACKGROUND: Artemisinins, commonly used to treat malaria, have shown activity against cytomegalovirus (CMV) in vitro, in an animal model, and in case reports; however, the in vivo anti-CMV activity has not been well investigated. OBJECTIVES: To evaluate whether artemisinins affect CMV shedding among subjects co-infected with CMV and malaria. STUDY DESIGN: A prospective observational study of children in Mali (6 month-10 year) presenting with fever. Urine samples were collected at day 0, 3, and 14 from children treated with artemether-lumefantrine (Coartem((r))) for malaria and those who had other illnesses not treated with Coartem. CMV DNA was quantified using a real-time PCR. Resulting urine viral loads were compared between the groups at three time points. RESULTS: 164 malaria cases and 143 non-malaria comparisons were enrolled. Eighty-one (49%) cases and 88 (62%) comparisons shed CMV at day 0. Day 0 and day 3 viral loads were similar, but at day 14 the median viral load of cases was lower than that of comparisons (360 vs 720 copies/mL or 2.56 vs 2.86 log10), p=0.059. A stratified analysis of day 0 high viral shedders (defined as >1000 copies/mL) showed significantly lower median viral load at day 14 among cases (490 copies/mL, 2.69 log10) vs comparisons (1200 copies/mL, 3.08 log10), p=0.045. CONCLUSION: A high rate of urinary CMV shedding was found in a malaria-endemic area. Among high virus shedders artemether-lumefantrine decreased urine viral load, but the effect was not observed when analysis of both high and low shedders was performed. These results support additional studies of artemisinin dosing and duration in CMV infection. PMID- 26895231 TI - Bodies as evidence: Mapping new terrain for teen pregnancy and parenting. AB - Predominant approaches to teen pregnancy focus on decreasing numbers of teen mothers, babies born to them, and state dollars spent to support their families. This overshadows the structural violence interwoven into daily existence for these young parents. This paper argues for the increased use of participatory visual methods to compliment traditional research methods in shifting notions of what counts as evidence in response to teen pregnancy and parenting. We present the methods and results from a body mapping workshop as part of 'Hear Our Stories: Diasporic Youth for Sexual Rights and Justice', a project that examines structural barriers faced by young parenting Latinas and seeks to develop relevant messaging and programming to support and engage youth. Body mapping, as an engaging, innovative participatory visual methodology, involves young parenting women and other marginalised populations in drawing out a deeper understanding of sexual health inequities. Our findings highlight the ways body mapping elicits bodies as evidence to understand young motherhood and wellbeing. PMID- 26895230 TI - Replication of Associations of Genetic Loci Outside the HLA Region With Susceptibility to Anti-Cyclic Citrullinated Peptide-Negative Rheumatoid Arthritis. AB - OBJECTIVE: Genetic polymorphisms within the HLA region explain only a modest proportion of anti-cyclic citrullinated peptide (anti-CCP)-negative rheumatoid arthritis (RA) heritability. However, few non-HLA markers have been identified so far. This study was undertaken to replicate the associations of anti-CCP-negative RA with non-HLA genetic polymorphisms demonstrated in a previous study. METHODS: The Rheumatoid Arthritis Consortium International densely genotyped 186 autoimmune-related regions in 3,339 anti-CCP-negative RA patients and 15,870 controls across 6 different populations using the Illumina ImmunoChip array. We performed a case-control replication study of the anti-CCP-negative markers with the strongest associations in that discovery study, in an independent cohort of anti-CCP-negative UK RA patients. Individuals from the arcOGEN Consortium and Wellcome Trust Case Control Consortium were used as controls. Genotyping in cases was performed using Sequenom MassArray technology. Genome-wide data from controls were imputed using the 1000 Genomes Phase I integrated variant call set release version 3 as a reference panel. RESULTS: After genotyping and imputation quality control procedures, data were available for 15 non-HLA single-nucleotide polymorphisms in 1,024 cases and 6,348 controls. We confirmed the known markers ANKRD55 (meta-analysis odds ratio [OR] 0.80; P = 2.8 * 10(-13) ) and BLK (OR 1.13; P = 7.0 * 10(-6) ) and identified new and specific markers of anti-CCP negative RA (prolactin [PRL] [OR 1.13; P = 2.1 * 10(-6) ] and NFIA [OR 0.85; P = 2.5 * 10(-6) ]). Neither of these loci is associated with other common, complex autoimmune diseases. CONCLUSION: Anti-CCP-negative RA and anti-CCP-positive RA are genetically different disease subsets that only partially share susceptibility factors. Genetic polymorphisms located near the PRL and NFIA genes represent examples of genetic susceptibility factors specific for anti-CCP negative RA. PMID- 26895232 TI - Derrisisoflavones H-K and One Isoflavan Derivative from Derris robusta. AB - Four hitherto unknown prenylated isoflavonoids, named derrisisoflavones H-K (1-4) and one new isoflavan, namely 6-hydroxyisosativan (5), were isolated from the ethanol extract of Derris robusta. Their structures were elucidated on the basis of extensive spectroscopic studies. To our knowledge, derrisisoflavones J (3) and K (4) are the first examples of hydroxyethylated isoflavonoid. PMID- 26895233 TI - Retinofugal Projections from Melanopsin-Expressing Retinal Ganglion Cells Revealed by Intraocular Injections of Cre-Dependent Virus. AB - To understand visual functions mediated by intrinsically photosensitive melanopsin-expressing retinal ganglion cells (mRGCs), it is important to elucidate axonal projections from these cells into the brain. Initial studies reported that melanopsin is expressed only in retinal ganglion cells within the eye. However, recent studies in Opn4-Cre mice revealed Cre-mediated marker expression in multiple brain areas. These discoveries complicate the use of melanopsin-driven genetic labeling techniques to identify retinofugal projections specifically from mRGCs. To restrict labeling to mRGCs, we developed a recombinant adeno-associated virus (AAV) carrying a Cre-dependent reporter (human placental alkaline phosphatase) that was injected into the vitreous of Opn4-Cre mouse eyes. The labeling observed in the brain of these mice was necessarily restricted specifically to retinofugal projections from mRGCs in the injected eye. We found that mRGCs innervate multiple nuclei in the basal forebrain, hypothalamus, amygdala, thalamus and midbrain. Midline structures tended to be bilaterally innervated, whereas the lateral structures received mostly contralateral innervation. As validation of our approach, we found projection patterns largely corresponded with previously published results; however, we have also identified a few novel targets. Our discovery of projections to the central amygdala suggests a possible direct neural pathway for aversive responses to light in neonates. In addition, projections to the accessory optic system suggest that mRGCs play a direct role in visual tracking, responses that were previously attributed to other classes of retinal ganglion cells. Moreover, projections to the zona incerta raise the possibility that mRGCs could regulate visceral and sensory functions. However, additional studies are needed to investigate the actual photosensitivity of mRGCs that project to the different brain areas. Also, there is a concern of "overlabeling" with very sensitive reporters that uncover low levels of expression. Light-evoked signaling from these cells must be shown to be of sufficient sensitivity to elicit physiologically relevant responses. PMID- 26895234 TI - Bayesian techniques for comparison of the test performance of PCR and culture for the identification of Campylobacter in enriched comminuted chicken samples. AB - AIMS: Using Bayesian methods that do not require the definition of a gold standard, the diagnostic sensitivity and specificity of a real-time polymerase chain reaction (PCR) assay are compared to those of an enriched culture assay for detection of Campylobacter in enriched comminuted chicken samples. METHODS AND RESULTS: Food Safety and Inspection Service comminuted chicken samples were collected from production facilities across the United States. Enriched samples were examined using a commercial real-time PCR kit and plated for culture. Allowing for conditional dependence between these approaches and defining relatively uninformed prior distributions, the 'no gold standard' Bayesian methods generated estimates of the means (95% credible interval) of the posterior distributions for sensitivity and specificity of the PCR as 93% (79, 100%) and 95% (87, 100%) respectively. The estimated sensitivity implies a mean false negative frequency of 7%. The estimated means of the posterior distributions for sensitivity and specificity of the culture assay were 91% (76, 100%) and 96% (88, 100%) respectively. In this case, the mean false negative frequency is 9%. Graphical comparisons of the posterior distributions with their corresponding prior distributions suggested only subtle differences in the sensitivities of both tests, but the posterior distributions for specificities are substantially more certain than the prior distributions. CONCLUSIONS: The study suggests that the commercial real-time PCR assay is a more sensitive screening test that would provide timelier negative test results. The modest 1% reduction in specificity of this PCR assay, as compared to an enriched culture assay, is less of a concern for regulatory testing programs if a culture-based confirmatory assay is applied to all presumptive positive samples. SIGNIFICANCE AND IMPACT OF THE STUDY: The sensitivity and specificity of a PCR assay and a culture assay for Campylobacter in comminuted poultry produced in the United States were estimated. The PCR assay was shown to be an appropriate alternative screening test. PMID- 26895235 TI - Wholistic Health Care: Evolutionary Conceptual Analysis. AB - While performing a data search to define "wholistic health care", it was evident that a definite gap existed in published literature. In addition, there are different definitions and several similar terms (whole person care, wholistic health, whole person health, wholism, etc.), which may cause confusion. The purpose of this paper was to present the analysis of "wholistic health care" using Rodgers' Evolutionary Method. The method allows for the historical and social nature of "wholistic health care" and how it changes over time. Attributes, antecedents, and consequences of wholistic health care were reduced using a descriptive matrix. In addition, attributes that consistently occurred in wholistic health care were presented as essential attributes. Definitions of Wholistic Health Care Provider(s), Wholistic Health, Wholistic Illness, Wholistic Healing, and Patient were created from the analysis of the literature review of attributes, antecedents, and consequences of wholistic health care. Wholistic Health Care is defined as the assessment, diagnosis, treatment and prevention of wholistic illness in human beings to maintain wholistic health or enhance wholistic healing. Identified wholistic health needs are addressed simultaneously by one or a team of allied health professionals in the provision of primary care, secondary care, and tertiary care. Wholistic health care is patient centered and considers the totality of the person (e.g., human development at a given age, genetic endowments, disease processes, environment, culture, experiences, relationships, communication, assets, attitudes, beliefs, and lifestyle behaviors). Patient centered refers to the patient as active participant in deciding the course of care. Essential attributes of wholistic health care are faith (spiritual) integrating, health promoting, disease managing, coordinating, empowering, and accessing health care. Wholistic health care may occur in collaboration with a faith-based organization to mobilize volunteers to support and promote individual, family, and community health. A gap existed in literature regarding the definition of wholistic health care. In addition, a lack of clarity was identified due to the use of the concept, similar or related concepts. Conceptual clarity was sought through identification and definitions of attributes, Powered by Editorial Manager((r)) and ProduXion Manager((r)) from Aries Systems Corporation antecedents, and consequences. The theoretical definition of wholistic health care and conceptual model can be used to support the presence of the concept, develop model-based applications, and consistently test effectiveness. PMID- 26895236 TI - What Mediates the Relationship Between Religious Service Attendance and Aspects of Well-Being? AB - Religious service attendance predicts increased well-being across a number of studies. It is not clear, however, whether this relationship is due to religious factors such as intrinsic religiosity or due to nonreligious factors such as social support or socially desirable responding. The purpose of the present study was to examine the relationship between religious service attendance and well being while simultaneously examining intrinsic religiosity, social support, and socially desirable responding as potential mediators of the relationship. A sample of 855 participants (71 % female, average age 19.5) completed questionnaires assessing religiosity, social support, socially desirable responding, and well-being. Path models were estimated using maximum likelihood estimation to analyze the data. Intrinsic religiosity was the strongest mediator of the relationship between religious service attendance and depressive and anxiety symptoms. This suggests that the mental health benefits of religious service attendance are not simply the result of increased social support or a certain response style on questionnaires; rather, it appears that the relationship is at least partly the result of people trying to live their religion in their daily lives. PMID- 26895238 TI - From discharge to readmission: Understanding the process from the patient perspective. AB - BACKGROUND: Patient engagement is critical in delivering high-quality care. However, literature investigating patient perspectives on readmissions is lacking. OBJECTIVES: To understand patients' beliefs and attitudes about 30-day readmissions and to elucidate areas for improvement aimed at reducing readmissions. DESIGN: In person survey. SETTING: Academic medical center and affiliated community hospital. PATIENTS: Patients with 30-day readmissions to medicine and cardiology services. MEASUREMENTS: Patient readiness, attitudes toward readmissions, discharge instructions, ambulatory resources, and follow-up care. RESULTS: Of 479 eligible patients approached for interviews, 230 (48%) were interviewed. Of these, 28% reported not feeling ready for discharge, and this correlated with inadequate symptom resolution, poor pain control, and concerns about self-care. Sixty-five percent remembered reviewing discharge paperwork, but over 22% could not identify critical information on this paperwork. Eighty-five percent reported having a primary doctor; however, only 56% of patients who received a contact number on discharge called a physician before returning to the hospital. One-third of patients knew where to obtain same-day care outside of the emergency room. Lastly, patients reported feeling more relieved than burdened upon readmission (7.7 [standard deviation {SD} 2.8) vs 5.9 [SD 3.4]; P < 0.001, scale of 1-10). CONCLUSIONS: By engaging readmitted patients we have illuminated areas for future interventions, including better symptom management and self-care planning before discharge, more clarity in discharge instructions, promoting awareness of outpatient resources, and improved alignment of patient and provider attitudes about readmissions. As the United States strives to reduce readmissions, attending to the patient perspective is critical in informing appropriate avenues for quality improvement. Journal of Hospital Medicine 2016;11:407-412. (c) 2016 Society of Hospital Medicine. PMID- 26895239 TI - Guidance for Providing Informed-Choice Counseling on Sexual Health for Women Interested in Pre-Exposure Prophylaxis in Kenya and South Africa. PMID- 26895237 TI - Systems Level Analyses Reveal Multiple Regulatory Activities of CodY Controlling Metabolism, Motility and Virulence in Listeria monocytogenes. AB - Bacteria sense and respond to many environmental cues, rewiring their regulatory network to facilitate adaptation to new conditions/niches. Global transcription factors that co-regulate multiple pathways simultaneously are essential to this regulatory rewiring. CodY is one such global regulator, controlling expression of both metabolic and virulence genes in Gram-positive bacteria. Branch chained amino acids (BCAAs) serve as a ligand for CodY and modulate its activity. Classically, CodY was considered to function primarily as a repressor under rich growth conditions. However, our previous studies of the bacterial pathogen Listeria monocytogenes revealed that CodY is active also when the bacteria are starved for BCAAs. Under these conditions, CodY loses the ability to repress genes (e.g., metabolic genes) and functions as a direct activator of the master virulence regulator gene, prfA. This observation raised the possibility that CodY possesses multiple functions that allow it to coordinate gene expression across a wide spectrum of metabolic growth conditions, and thus better adapt bacteria to the mammalian niche. To gain a deeper understanding of CodY's regulatory repertoire and identify direct target genes, we performed a genome wide analysis of the CodY regulon and DNA binding under both rich and minimal growth conditions, using RNA-Seq and ChIP-Seq techniques. We demonstrate here that CodY is indeed active (i.e., binds DNA) under both conditions, serving as a repressor and activator of different genes. Further, we identified new genes and pathways that are directly regulated by CodY (e.g., sigB, arg, his, actA, glpF, gadG, gdhA, poxB, glnR and fla genes), integrating metabolism, stress responses, motility and virulence in L. monocytogenes. This study establishes CodY as a multifaceted factor regulating L. monocytogenes physiology in a highly versatile manner. PMID- 26895241 TI - Catecholamine Metabolism Induces Mitochondrial DNA Deletions and Leads to Severe Adrenal Degeneration during Aging. AB - BACKGROUND: Aging is a multifactorial process characterized by organ loss of function and degeneration, but the mechanisms involved remain elusive. We have shown recently that catecholamine metabolism drives the accumulation of mitochondrial DNA (mtDNA) deletions in dopaminergic cells, which likely contribute to their degeneration during aging. Here we investigated whether the well-documented degeneration and altered function of adrenals during aging is linked to catecholamine production in the medulla followed by accumulation of mtDNA deletions. MATERIAL AND METHODS: We analyzed adrenal medullary and cortical samples of both murine and human origin covering a wide range of ages for mtDNA deletion content, mtDNA copy number, mitochondrial and cellular integrity as well as aging-related tissue changes such as fibrosis. RESULTS: Indeed, we demonstrate in mice and humans that the adrenal medulla accumulates a strikingly high amount of mtDNA deletions with age, causing mitochondrial dysfunction in the adrenal medulla, but also in the cortex, accompanied by apoptosis and, more importantly, by severe inflammation and remarkable fibrosis. Additionally, a concomitant and dramatic loss of medullary and cortical cells is observed in old animals. CONCLUSION: Our results show that accumulation of mtDNA deletions, and the ensuing mitochondrial dysfunction, is a hallmark of adrenal aging, further strengthening the hypothesis that catecholamine metabolism is detrimental to mtDNA integrity, mitochondrial function and cell survival. Moreover, the cell loss potentially induced by mitochondrial dysfunction could explain the decline in adrenal hormonal and steroidal secretion during aging. PMID- 26895240 TI - Dengue Virus Nonstructural Protein 5 (NS5) Assembles into a Dimer with a Unique Methyltransferase and Polymerase Interface. AB - Flavivirus nonstructural protein 5 (NS5) consists of methyltransferase (MTase) and RNA-dependent RNA polymerase (RdRp) domains, which catalyze 5'-RNA capping/methylation and RNA synthesis, respectively, during viral genome replication. Although the crystal structure of flavivirus NS5 is known, no data about the quaternary organization of the functional enzyme are available. We report the crystal structure of dengue virus full-length NS5, where eight molecules of NS5 are arranged as four independent dimers in the crystallographic asymmetric unit. The relative orientation of each monomer within the dimer, as well as the orientations of the MTase and RdRp domains within each monomer, is conserved, suggesting that these structural arrangements represent the biologically relevant conformation and assembly of this multi-functional enzyme. Essential interactions between MTase and RdRp domains are maintained in the NS5 dimer via inter-molecular interactions, providing evidence that flavivirus NS5 can adopt multiple conformations while preserving necessary interactions between the MTase and RdRp domains. Furthermore, many NS5 residues that reduce viral replication are located at either the inter-domain interface within a monomer or at the inter-molecular interface within the dimer. Hence the X-ray structure of NS5 presented here suggests that MTase and RdRp activities could be coordinated as a dimer during viral genome replication. PMID- 26895242 TI - Human mesenchymal stem cell responses to hydrostatic pressure and shear stress. AB - The effects of mechanical stimuli to which cells are exposed in vivo are, at best, incompletely understood; in this respect, gene-level information regarding cell functions which are pertinent to new tissue formation is of special interest and importance in applications such as tissue engineering and tissue regeneration. Motivated by this need, the present study investigated the early responses of human mesenchymal stem cells (hMSCs) to intermittent shear stress (ISS) and to cyclic hydrostatic pressure (CHP) simulating some aspects of the biological milieu in which these cells exist in vivo. Production of nitric oxide (NO) and mRNA expression of several known mechanosensitive genes as well as ERK1/2 activation in the hMSC response to the two mechanical stimuli tested were monitored and compared. NO production depended on the type of the mechanical stimulus to which the hMSCs were exposed and was significantly higher after exposure to ISS than to CHP. At the conditions of NO peak release (i.e., at 0.7 Pa for ISS and 50,000 Pa for CHP), ISS was more effective than CHP in up regulating mechanosensitive genes. ERK1/2 was activated by ISS but not by CHP. The present study is the first to report that PGTS2, IER3, EGR1, IGF1, IGFBP1, ITGB1, VEGFA and FGF2 are involved in the response of hMSCs to ISS. These findings establish that, of the two mechanical stimuli tested, ISS is more effective than CHP in triggering expression of genes from hMSCs which are bioactive and pertinent to several cell functions (such as cell differentiation and release of specific growth factors and cytokines) and also to tissue-related processes such as wound healing. PMID- 26895243 TI - Current status and regulatory perspective of chimeric antigen receptor-modified T cell therapeutics. AB - Chimeric antigen receptor-modified T cells (CAR-T) have emerged as a new modality for cancer immunotherapy due to their potent efficacy against terminal cancers. CAR-Ts are reported to exert higher efficacy than monoclonal antibodies and antibody-drug conjugates, and act via mechanisms distinct from T cell receptor engineered T cells. These cells are constructed by transducing genes encoding fusion proteins of cancer antigen-recognizing single-chain Fv linked to intracellular signaling domains of T cell receptors. CAR-Ts are classified as first-, second- and third-generation, depending on the intracellular signaling domain number of T cell receptors. This review covers the current status of CAR-T research, including basic proof-of-concept investigations at the cell and animal levels. Currently ongoing clinical trials of CAR-T worldwide are additionally discussed. Owing to the lack of existing approved products, several unresolved concerns remain with regard to safety, efficacy and manufacturing of CAR-T, as well as quality control issues. In particular, the cytokine release syndrome is the major side-effect impeding the successful development of CAR-T in clinical trials. Here, we have addressed the challenges and regulatory perspectives of CAR T therapy. PMID- 26895244 TI - Tannic acid-mediated green synthesis of antibacterial silver nanoparticles. AB - The search for novel antibacterial agents is necessary to combat microbial resistance to current antibiotics. Silver nanoparticles (AgNPs) have been reported to be effective antibacterial agents. Tannic acid is a polyphenol compound from plants with antioxidant and antibacterial activities. In this report, AgNPs were prepared from silver ions by tannic acid-mediated green synthesis (TA-AgNPs). The reaction process was facile and involved mixing both silver ions and tannic acid. The absorbance at 423 nm in the UV-Visible spectra demonstrated that tannic acid underwent a reduction reaction to produce TA-AgNPs from silver ions. The synthetic yield of TA-AgNPs was 90.5% based on inductively coupled plasma mass spectrometry analysis. High-resolution transmission electron microscopy and atomic force microscopy images indicated that spherical-shaped TA AgNPs with a mean particle size of 27.7-46.7 nm were obtained. Powder high resolution X-ray diffraction analysis indicated that the TA-AgNP structure was face-centered cubic with a zeta potential of -27.56 mV. The hydroxyl functional groups of tannic acid contributed to the synthesis of TA-AgNPs, which was confirmed by Fourier transform infrared spectroscopy. The in vitro antibacterial activity was measured using the minimum inhibitory concentration (MIC) method. The TA-AgNPs were more effective against Gram-negative bacteria than Gram positive bacteria. The MIC for the TA-AgNPs in all of the tested strains was in a silver concentration range of 6.74-13.48 MUg/mL. The tannic acid-mediated synthesis of AgNPs afforded biocompatible nanocomposites for antibacterial applications. PMID- 26895245 TI - Effects of bisphenol-A on male reproductive success in adult Kadaknath chicken. AB - Bisphenol-A (BPA) adversely affects human and animal reproductive success in many ways, but this information is scant on birds. In the present study, we investigated the reproductive toxicity of BPA in adult Kadaknath chicken using two BPA dosages orally (1 or 5 mg/kg body weight) for seven weeks. In order to assess BPA toxicity, sperm functions, fertilizing ability, serum testosterone concentration and testis histopathology were measured in treated and control chickens. The semen volume was highest in birds exposed to 1mg/kg body weight BPA compared to other groups. 5 mg/kg body weight BPA reduced sperm concentration significantly more than other treatment and controls. However, overall fertility and testis histology were unaffected. These results indicate that BPA adversely affects sperm characteristics in adult kadaknath chicken without affecting fertilization potential. PMID- 26895246 TI - Suppression of activation of muscle sympathetic nerve during non-noxious local cooling after the end of local cooling in normal adults. AB - PURPOSE: While non-noxious local cooling is widely used in physical medicine, its effect on muscle sympathetic nerve activity (MSNA) and cardiovascular regulation are not clear. The purpose of the present study was to assess the responses of MSNA, blood pressure (BP), heart rate (HR) and local blood flow during non noxious local cooling. METHODS: The study included two protocols. Both protocols consisted of 10-min rest in supine position, followed by 15-min local cooling (15 degrees C) of the shin and anterior foot, and 20-min recovery. MSNA of the right common peroneal nerve, BP, HR, and shin skin temperature (TSK) were recorded in eight men in the first protocol, while leg blood flow (LBF) was measured in the same subjects by strain-gauge plethysmography in the second protocol. RESULTS: TSK gradually decreased from 31.5 +/- 0.02 to 16.0 +/- 1.01 degrees C (mean +/- SEM) during local cooling, and gradually increased after the end of local cooling. No subject complained of pain, and BP and HR remained constant. The MSNA burst rate increased significantly (p < 0.05) to 141.1 +/- 12.5 % during local cooling, but decreased significantly (p < 0.05) to 73.6 +/- 5.9 % during the recovery period. Total MSNA also increased to 148.0 +/- 14.2 % (p < 0.05) during local cooling, and decreased to 74.0 +/- 13.9 % (p < 0.05) at recovery. LBF remained constant through the experiment. CONCLUSIONS: The results suggest that MSNA is activated by non-noxious local cooling, and attenuated after the end of local cooling without any changes in HR and BP. PMID- 26895247 TI - Association between Metabolic Syndrome and Cancer. AB - Growing data show the association of metabolic syndrome (MetS) or its components with cancer development and cancer-related mortality. It is suggested that in MetS and cancer association, insulin resistance and insulin-like growth factor 1 system play a key role, especially adipokines secreted from visceral adipocytes, free fatty acids and aromatase activity contribute to this process. It is also reported that MetS has a link with colorectal, breast, endometrial, pancreas, primary liver and, although controversial, prostate cancer. Although every component of MetS is known to have an association with cancer development, it is still debated whether the effects of these components are additive or synergistic. On the other hand, in the association between MetS and cancer, the role of antidiabetic and antihypertensive treatments including thiazolidinedione, insulin, angiotensin receptor blockers is also suggested. The primary approach in MetS-cancer relation is to prevent risk factors. Life style changes including weight loss and a healthy diet are known to decrease cancer risk in normal population. It is postulated that an insulin-sensitizing agent, metformin, has cancer-preventing effects on diabetic patients. This review discusses the relationship between MetS and cancer from different aspects and examines this relationship in some of the cancers suggested to be linked with MetS. PMID- 26895249 TI - The non-structural protein Nsp2TF of porcine reproductive and respiratory syndrome virus down-regulates the expression of Swine Leukocyte Antigen class I. AB - Porcine reproductive and respiratory syndrome virus (PRRSV) is arguably the most economically-important global swine pathogen. Here we demonstrated that PRRSV down-regulates Swine Leukocyte Antigen class I (SLA-I) expression in porcine alveolar macrophages, PK15-CD163 cells and monocyte-derived dendritic cells. To identify the viral protein(s) involved in SLA-I down-regulation, we tested all 22 PRRSV structural and non-structural proteins and identified that Nsp1alpha and Nsp2TF, and GP3 significantly down-regulated SLA-I expression with Nsp2TF showing the greatest effect. We further generated a panel of mutant viruses in which the Nsp2TF protein synthesis was abolished, and found that the two mutants with disrupted -2 ribosomal frameshifting elements and additional stop codons in the TF domain were unable to down-regulate SLA-I expression. Additionally we demonstrated that the last 68 amino acids of TF domain in Nsp2TF are critical for this function. Collectively, the results indicate a novel function of Nsp2TF in negative modulation of SLA-I expression. PMID- 26895248 TI - Metabolic profiling during HIV-1 and HIV-2 infection of primary human monocyte derived macrophages. AB - We evaluated cellular metabolism profiles of HIV-1 and HIV-2 infected primary human monocyte-derived macrophages (MDMs). First, HIV-2 GL-AN displays faster production kinetics and greater amounts of virus as compared to HIV-1s: YU-2, 89.6 and JR-CSF. Second, quantitative LC-MS/MS metabolomics analysis demonstrates very similar metabolic profiles in glycolysis and TCA cycle metabolic intermediates between HIV-1 and HIV-2 infected macrophages, with a few notable exceptions. The most striking metabolic change in MDMs infected with HIV-2 relative to HIV-1-infected MDMs was the increased levels of quinolinate, a metabolite in the tryptophan catabolism pathway that has been linked to HIV/AIDS pathogenesis. Third, both HIV-1 and HIV-2 infected MDMs showed elevated levels of ribose-5-phosphate, a key metabolic component in nucleotide biosynthesis. Finally, HIV-2 infected MDMs display increased dNTP concentrations as predicted by Vpx-mediated SAMHD1 degradation. Collectively, these data show differential metabolic changes during HIV-1 and HIV-2 infection of macrophages. PMID- 26895251 TI - [Subtalar arthrodesis]. AB - OBJECTIVE: Realignment and stabilization of the hindfoot by subtalar joint arthrodesis. INDICATIONS: Idiopathic/posttraumatic arthritis, inflammatory arthritis of the subtalar joint with/without hindfoot malalignment. Optional flatfoot/cavovarus foot reconstruction. CONTRAINDICATIONS: Inflammation, vascular disturbances, nicotine abuse. SURGICAL TECHNIQUE: Approach dependent on assessment. Lateral approach: Supine position. Incision above the sinus tarsi. Exposure of subtalar joint. Removal of cartilage and breakage of the subchondral sclerosis. In valgus malalignment, interposition of corticocancellous bone segment; in varus malalignment resection of bone segment from the calcaneus. Reposition and temporarily stabilization with Kirschner wires. Imaging of hindfoot alignment. Stabilization with cannulated screws. Posterolateral approach: Prone position. Incision parallel to the lateral Achilles tendon border. Removal of cartilage and breakage of subchondral sclerosis. Medial approach: Supine position. Incision just above and parallel to the posterior tibial tendon. Removal of cartilage and breakage of subchondral sclerosis. Stabilization with screws. POSTOPERATIVE MANAGEMENT: Lower leg walker with partial weightbearing. Active exercises of the ankle. After a 6-week X-ray, increase of weightbearing. Full weightbearing not before 8 weeks; with interpositioning bone grafts not before 10-12 weeks. Stable walking shoes. Active mobilization of the ankle. RESULTS: Of 43 isolated subtalar arthrodesis procedures, 5 wound healing disorders and no infections developed. Significantly improved AOFAS hindfood score. Well-aligned heel observed in 34 patients; 5 varus and 2 valgus malalignments. Sensory disturbances in 8 patients; minor ankle flexion limitations. Full bone healing in 36 subtalar joints, pseudarthrosis in 4 patients. PMID- 26895250 TI - The Type III Secretion System-Related CPn0809 from Chlamydia pneumoniae. AB - Chlamydia pneumoniae is an intracellular Gram-negative bacterium that possesses a type III secretion system (T3SS), which enables the pathogen to deliver, in a single step, effector proteins for modulation of host-cell functions into the human host cell cytosol to establish a unique intracellular niche for replication. The translocon proteins located at the top of the T3SS needle filament are essential for its function, as they form pores in the host-cell membrane. Interestingly, unlike other Gram-negative bacteria, C. pneumoniae has two putative translocon operons, named LcrH_1 and LcrH_2. However, little is known about chlamydial translocon proteins. In this study, we analyzed CPn0809, one of the putative hydrophobic translocators encoded by the LcrH_1 operon, and identified an 'SseC-like family' domain characteristic of T3S translocators. Using bright-field and confocal microscopy, we found that CPn0809 is associated with EBs during early and very late phases of a C. pneumoniae infection. Furthermore, CPn0809 forms oligomers, and interacts with the T3SS chaperone LcrH_1, via its N-terminal segment. Moreover, expression of full-length CPn0809 in the heterologous host Escherichia coli causes a grave cytotoxic effect that leads to cell death. Taken together, our data indicate that CPn0809 likely represents one of the translocon proteins of the C. pneumoniae T3SS, and possibly plays a role in the translocation of effector proteins in the early stages of infection. PMID- 26895252 TI - Self-induced growth of vertical GaN nanowires on silica. AB - We study the self-induced growth of GaN nanowires on silica. Although the amorphous structure of this substrate offers no possibility of an epitaxial relationship, the nanowires are remarkably aligned with the substrate normal whereas, as expected, their in-plane orientation is random. Their structural and optical characteristics are compared to those of GaN nanowires grown on standard crystalline Si (111) substrates. The polarity inversion domains are much less frequent, if not totally absent, in the nanowires grown on silica, which we find to be N-polar. This work demonstrates that high-quality vertical GaN nanowires can be elaborated without resorting to bulk crystalline substrates. PMID- 26895253 TI - Advances in the Development of Disease-Modifying Treatments for Amyotrophic Lateral Sclerosis. AB - Amyotrophic lateral sclerosis (ALS) is a progressive adult-onset, neurodegenerative disease characterized by the degeneration of upper and lower motor neurons. Over recent years, numerous genes ha ve been identified that promote disease pathology, including SOD1, TARDBP, and the expanded hexanucleotide repeat (GGGGCC) within C9ORF72. However, despite these major advances in identifying genes contributing to ALS pathogenesis, there remains only one currently approved therapeutic: the glutamate antagonist, riluzole. Seminal breakthroughs in the pathomechanisms and genetic factors associated with ALS have heavily relied on the use of rodent models that recapitulate the ALS phenotype; however, while many therapeutics have proved to be significant in animal models by prolonging life and rescuing motor deficits, they have failed in human clinical trials. This may be due to fundamental differences between rodent models and human disease, the fact that animal models are based on overexpression of mutated genes, and confounding issues such as difficulties mimicking the dosing schedules and regimens implemented in mouse models to humans. Here, we review the major pathways associated with the pathology of ALS, the rodent models engineered to test efficacy of candidate drugs, the advancements being made in stem cell therapy for ALS, and what strategies may be important to circumvent the lack of successful translational studies in the clinic. PMID- 26895255 TI - The influence of foot and ankle injury patterns and treatment delays on outcomes in a tertiary hospital; a one-year prospective observation. AB - BACKGROUND: Ankle and foot fractures are amongst the most common injuries, and patterns may vary from primary care set up to tertiary hospitals. Severe foot injuries are projected to have significantly worse outcomes and surgical delays are thought to alter prognosis. METHODS: All patients with foot and ankle trauma were prospectively evaluated at a Tertiary trauma centre over one year. The incidence, fracture patterns, risk factors, and outcomes were evaluated, and cases were divided into simple foot injuries (FASS <= 3) and severe foot injuries (FASS>3). Injury mechanisms, associated injuries, and delays in treatment were evaluated, and outcomes were analyzed using Visual-Analogue Scale Foot and Ankle (VASFA), Maryland Foot Score (MFS) and Foot and ankle disability index (FADI). RESULTS: 294 Foot and Ankle injuries (51 females, 243 males) were encountered in 2919 trauma cases (incidence of 10%). 80 patients (27.2%) had simple foot injuries and 214 (72.8%) had severe foot injuries. 29 patients (9.9%) were below 18 years; most (65.3%) patients were between 18 and 45 years age. Road traffic accident was most commonest mode of injury, with ankle fractures (30.6%) the most common. Metatarsal fractures (27.9%) and calcaneal fractures (21.4%) were 2nd and 3rd most common injuries in the foot. Surgical delay averaged 1 day in both severe and simple injuries. Injury led to 32 (10.9%) below knee amputations. Outcome evaluation in 127 (91 severe, 36 simple injuries) patients showed mean Maryland foot score of 89.30 in simple injury group and 84.87 in severe injury group. Mean VASFA score was 82.87 (simple) and 81.87 in severe injury, and mean FADI score was 93.13 (simple) and 91.05 (severe injury). More detailed analysis revealed that more good scores (64.4%) were documented in severe injuries group, and more excellent scores (52.8%) in simple injuries group. CONCLUSION: Foot injuries constitute 10% of all orthopaedic trauma at tertiary hospitals; Majority of them are severe foot injuries, with 68.7% being open injuries. Surgical delay was similar in simple and severe foot and ankle injuries. Outcomes of severe injuries were similar to simple foot and ankle injuries, reflecting on the quality of care that could be administered to them when they present to tertiary hospitals. PMID- 26895256 TI - Removal of naphthalene and phenanthrene using aerobic membrane bioreactor. AB - The removal of polycyclic aromatic hydrocarbons by membrane bioreactor (MBR) under aerobic conditions had been studied using naphthalene (NAP) and phenanthrene (PHE) as model compounds. Three MBRs with submerged ultra-filtration hollow fiber membranes were operated applying different operational conditions during 6.5 months. Complete NAP and PHE removal was obtained applying loads of 7 gNAP kgTSS(-1) day(-1) and 0.5 gPHE kgTSS(-1) day(-1), while the organic loading rate was adjusted to 0.26 kgCOD kgTSS(-1) day(-1), with the biomass concentration being 6000 mgTSS L(-1), the hydraulic retention time (HRT) 8 h and the solids retention time (SRT) 30 days. Load increases, as well as HRT and SRT reductions, affected the NAP and PHE removals. Biodegradation was found to be the major NAP and PHE removal mechanism. There was no NAP accumulation in the biomass. Low PHE quantities remain sorbed in the biomass and the contribution of the sorption in the removal of this compound was estimated to be less than 0.01 %. The volatilization does not contribute to the PHE removal in MBRs, but the contribution of NAP volatilization can reach up to 0.6 % when HRT of 8 h is applied. PMID- 26895254 TI - Potential of Oxytocin in the Treatment of Schizophrenia. AB - Schizophrenia is a heterogeneous, debilitating disorder characterized by three distinct sets of clinical features: positive symptoms, negative symptoms, and cognitive deficits. Extant antipsychotic drugs have been most successful at treating the positive symptoms of patients with schizophrenia but have minimal therapeutic effects on negative symptoms and cognitive deficits, which are the symptoms that best predict the poor prognosis of these patients. Therefore, there has been a major effort towards identifying compounds that alleviate these symptoms. Oxytocin (OT) is a nonapeptide that regulates peripheral reproductive relevant functions, and also acts as a neurotransmitter in the brain. Converging evidence from both preclinical and clinical research suggests that OT may have therapeutic efficacy for the positive symptoms, negative symptoms, and cognitive deficits of schizophrenia. In the majority of the small, randomized, placebo controlled clinical trials conducted to date, OT has shown particular promise in its potential to treat the intractable negative symptoms and social cognitive deficits exhibited by most of the patients with this debilitating disorder. In this leading article, we summarize the clinical evidence relevant to (1) endogenous OT and schizophrenia, and (2) the putative therapeutic effects of OT on each of the three clinical domains. PMID- 26895257 TI - Topical colloidal indocyanine green-mediated photodynamic therapy for treatment of basal cell carcinoma. AB - Indocyanine green (ICG) is a near-IR fluorescent dye with a great potential for application as photosensitizer in topical photodynamic therapy (PDT) of skin diseases. Despite its merits, its use has been hampered by its high degradation rate. Therefore, in the current article, ICG was encapsulated in a vesicular colloidal nanocarrier (transfersomes), with the aim of enhancing its therapeutic efficacy. Transfersomes were characterized for their entrapment efficiency, particle size, zeta potential, morphology, in vitro release and histopathological effect on mice skin. A pilot clinical study was conducted to test its therapeutic potential for PDT of basal cell carcinoma (BCC). Transfersomal ICG displayed particle size (~125 nm) and a negative zeta potential (~-31 mV). Transfersomes were also able to sustain the release of ICG >2 h. Upon incorporation of transfersomal ICG in gel form, it was found to maintain the normal histology of mice skin post-irradiation with diode laser 820 nm. Moreover, ICG transfersomal PDT achieved 80% clearance rate for BCC patients with minimal pain reported during treatment. The previous findings suggest that transfersomal nanoencapsulated ICG is a promising treatment modality for BCC. PMID- 26895258 TI - Editors' Notes. PMID- 26895259 TI - Introduction: The Golden Triangle for Examining Leadership Developmental Readiness. AB - This introduction includes the history of the leadership field that resulted in the creation of the developmental readiness construct, which represents readiness of the leader as well as followers, peers, and the target leader's leader, and how context is to be developed through some form of leadership intervention. PMID- 26895260 TI - In Pursuit: Mastering Leadership Through Leader Developmental Readiness. AB - This chapter defines leader developmental readiness, presents a conceptual model, and discusses implications for practitioners supporting leaders before college, during college, and in early career stages. PMID- 26895261 TI - The Role of Passion and Purpose in Leader Developmental Readiness. AB - The founder of TOMS Shoes, Blake Mycoskie, and the late Apple cofounder and CEO, Steve Jobs, model the role of passion and purpose in leader developmental readiness. PMID- 26895262 TI - Exploring Leader Identity and Development. AB - Taking on a leader identity can be a motivating force for pursuing leader development. This chapter explores the reciprocal and recursive nature of identity development and leader development, emphasizing how shifting views of self influence one's motivation to develop as a leader. PMID- 26895263 TI - Motivation to Develop as a Leader. AB - This chapter explains the role of motivation in readying leaders to succeed. Suggestions are also offered for leadership developers in harnessing motivational factors to optimize their educational programs. PMID- 26895264 TI - Orienting Oneself for Leadership: The Role of Goal Orientation in Leader Developmental Readiness. AB - The ways in which individuals approach achievement situations influence their use of self-management activities such as goal setting, feedback seeking, and developmental strategies, and ultimately impact success in leader development. PMID- 26895265 TI - Leadership and Leader Developmental Self-Efficacy: Their Role in Enhancing Leader Development Efforts. AB - This chapter describes the role of two types of self-efficacy-leader self efficacy and leader developmental efficacy-for enhancing leadership development. Practical implications for designing and developing leadership programs that take into account these two types of self-efficacy are discussed. PMID- 26895266 TI - Thinking About Thinking About Leadership: Metacognitive Ability and Leader Developmental Readiness. AB - This chapter describes the role of metacognitive ability in leadership development while providing practical ideas and tools for the development of metacognitive abilities for current and future leaders. PMID- 26895267 TI - Context Matters: Support for Leader Developmental Readiness. AB - Leader developers need to consider support for leader developmental readiness by examining organizational culture, job design and rewards, social support, and availability and structure of leader development programming. PMID- 26895269 TI - A Critical Analysis of Concentration and Competition in the Indian Pharmaceutical Market. AB - OBJECTIVES: It can be argued that with several players marketing a large number of brands, the pharmaceutical market in India is competitive. However, the pharmaceutical market should not be studied as a single market but, as a sum total of a large number of individual sub-markets. This paper examines the methodological issues with respect to defining the relevant market involved in studying concentration in the pharmaceutical market in India. Further, we have examined whether the Indian pharmaceutical market is competitive. METHODS: Indian pharmaceutical market was studied using PharmaTrac, the sales audit data from AIOCD-AWACS, that organises formulations into 5 levels of therapeutic classification based on the EphMRA system. The Herfindahl-Hirschman Index (HHI) was used as the indicator of market concentration. We calculated HHI for the entire pharmaceutical market studied as a single market as well as at the five different levels of therapeutic classification. RESULTS AND DISCUSSION: Whereas the entire pharmaceutical market taken together as a single market displayed low concentration (HHI = 226.63), it was observed that if each formulation is defined as an individual sub-market, about 69 percent of the total market in terms of market value displayed at least moderate concentration. Market should be defined taking into account the ease of substitutability. Since, patients cannot themselves substitute the formulation prescribed by the doctor with another formulation with the same indication and therapeutic effect, owing to information asymmetry, it is appropriate to study market concentration at the narrower levels of therapeutic classification. PMID- 26895270 TI - The Scale of Self-Efficacy Expectations of Adherence to Antiretroviral Treatment: A Tool for Identifying Risk for Non-Adherence to Treatment for HIV. AB - BACKGROUND: Identification of risk for non-adherence to treatment is a challenge for personalized care for people living with HIV. Standardized questionnaires of patients' expectations of their capability to overcome obstacles for treatment adherence may be used as a pre-screening for risk identification. A scale of self efficacy expectations of adherence to antiretroviral treatment (SEA-ART scale) was previously developed. This study assesses the scale validity in predicting non-adherence to ART in adults living with HIV. METHODS AND FINDINGS: A prospective cohort study applied a 21-item SEA-ART scale to 275 adults in ART treatment at an outpatient public service for HIV in Southern Brazil. ART medications taken were assessed at one-month follow-up; ART adherence was devised as an intake of 95% and more of the prescribed medication. A SEA-ART score was calculated by adding up the scores of all items. Multivariable logistic regression and the Area Under the Receiver-Operating-Characteristic Curve (AUROC) were applied to examine the ability of the SEA-ART score to predict non-adherence at follow-up. The SEA-ART score varied from 21 to 105; mean 93.9; median 103.0. Non-adherence was 30.3% (n = 81/267). The odds of non-adherence was 8% lower for each unit increase of the SEA-ART score; after adjustment for age, sex, formal education and time in treatment (OR = 0.92; 95%CI 0.90-0.95; LRT for linear trend, p = 0.002). The AUROC was 0.80 (95%CI 0.73-0.87; p<0.001). The SEA-ART optimal cut-off value was 101, providing a sensitivity of 76.5%, a specificity of 73.1%, a positive predictive value of 55.4% and a negative predictive value of 87.7%. There was no evidence of difference in sensitivity, and specificity among groups organized by age, gender, formal education and time in treatment. CONCLUSIONS: The SEA-ART scale appears to have a good capacity to discriminate between adherents and non-adherents at one-month follow-up. Further studies should confirm these results in other populations. PMID- 26895271 TI - News in Cellular Allergology: A Review of the Human Mast Cell and Basophil Granulocyte Literature from January 2013 to May 2015. AB - Mast cell activation releases the mediators associated with type I allergy. As such, the study of mast cell activation is critical for understanding the allergic reaction, and for developing methods to control it. Importantly, another ligand receptor pair (compound 48/80 and MRGPRX2) that activates mast cells in addition to allergen-IgE-FcepsilonRI has been identified. As mast cells mature in tissue from hematopoietic stem cells, their physiology and pathophysiology is difficult to study. Mast cell lines and mast cells cultured from stem cells are often studied instead of tissue mast cells. There has been some progress in the description of the mechanism of the activation of mast cells, substances limiting mast cell activation and in the catalogue of proteases that mast cells express. Basophil granulocytes express FcepsilonRI, bind IgE and respond to allergen crosslinking in a very similar fashion to mast cells. In the recent literature, basophils were mistakenly described as antigen-presenting cells; this has convincingly been disputed in a number of subsequent publications. Their function in physiology and pathophysiology is not known, but they are frequently used to document allergic sensitisation in the basophil activation test. Significant progress has been made in documenting the relevance of basophil activation as a second-line test in allergy diagnosis. Basophil reactivity and sensitivity may reflect symptom severity and allergen threshold, and are used to document and monitor allergy. The physiology and pathophysiology of allergic effector cells remain an important area of research. PMID- 26895272 TI - A retrospective analysis of vision correction and safety in keratoconus patients wearing Toris K soft contact lenses. AB - The purpose of this study was to investigate the efficacy and safety of the Toris K silicone hydrogel contact lens (SwissLens; Prilly, Switzerland) in keratoconus patients. A database with information on 50 keratoconus patients (64 eyes) fitted with Toris K soft contact lenses over a 2-year period was retrospectively reviewed. Demographic data, prefitting refraction, the reason for choosing the Toris K soft contact lens, uncorrected visual acuity (UCVA), best spectacle corrected visual acuity (BSCVA), best-corrected visual acuity with a rigid gas permeable lens (BCVA RGP), best-corrected visual acuity with the Toris K lens (BCVA Toris K), and complications were evaluated. The mean age +/- standard deviation at the time of fitting was 27.92 +/- 9.86 years. The mean spherical refractive power was -4.62 +/- 6.53 dioptres, and the mean cylinder was -3.78 +/- 2.43 dioptres. The most common reason for using Toris K soft contact lenses was an inability to fit the patient with a RGP contact lens. There was a statistically significant difference between UCVA and BCVA Toris K (p = 0.0001), as well as between BSCVA and BCVA Toris K (p = 0.0001). However, there was no statistically significant difference between BCVA Toris K and BCVA RGP (p = 0.20). Superficial punctate keratitis and giant papillary conjunctivitis were the most common complications. The Toris K contact lens is a viable alternative for the optical management of all grades of keratoconus. The Toris K soft contact lens is a promising alternative for the visual rehabilitation of keratoconus patients who cannot tolerate RGP lenses or achieve a good fit. PMID- 26895273 TI - External ophthalmomyiasis: a case series and review of ophthalmomyiasis in Turkey. AB - Ophthalmomyiasis externa is the infestation of the superficial external ocular structures by fly larvae. This is a particularly rare condition, which has nevertheless been reported in several countries worldwide. It is common in sheep farming areas, especially in Mediterranean countries. The patients may present with classic conjunctivitis, pseudomembranous conjunctivitis, conjunctival hemorrhages, punctuate keratitis, keratouveitis, and eyelid edema with erythema. Herein, we present three cases of external ophthalmomyiasis caused by Oestrus ovis larvae and review ophthalmomyiasis cases reported from Turkey. PMID- 26895274 TI - Effects of different bulking agents on the maturity, enzymatic activity, and microbial community functional diversity of kitchen waste compost. AB - Aerobic composting is an effective method for the disposal and utilization of kitchen waste. However, the addition of a bulking agent is necessary during kitchen waste composting because of its high moisture content and low C/N ratio. In order to select a suitable bulking agent, we investigated the influence of leaf litter (LL), sawdust (SD), and wheat straw (WS) on the enzymatic activity, microbial community functional diversity, and maturity indices during the kitchen waste composting process. The results showed that the addition of WS yielded the highest maturity (the C/N ratio decreased from 25 to 13, T value = 0.5, and germination index (GI) = 114.7%), whereas the compost containing SD as a bulking agent had the lowest maturity (GI = 32.4%). The maximum cellulase and urease activities were observed with the WS treatment on day 8, whereas the SD treatment had the lowest cellulase activity and the LL treatment had the lowest urease activity. The compost temperature and microbial activity (as the average well color development) showed that bulking the composts with SD prolonged the composting process. The diversity index based on the community-level physiological profile showed that the composts bulked with LL and WS had greater microbial community functional diversity compared with those bulked with SD. Thus, the maturity indexes and enzymatic activities suggest that WS is a suitable bulking agent for use in kitchen waste composting systems. PMID- 26895275 TI - The Effect of Metformin on Hypothalamic-Pituitary-Thyroid Axis Activity in Women with Interferon-Induced Hypothyroidism: A Pilot Study. AB - BACKGROUND: One of the most frequent adverse effects of interferon-alpha therapy is thyroiditis. Metformin was found to improve insulin sensitivity in hepatitis C patients, as well as to reduce elevated thyrotropin levels in patients with hypothyroidism. The aim of this study was to investigate the effect of metformin on hypothalamic-pituitary-thyroid axis activity in patients with interferon induced thyroiditis. METHODS: The study included 2 matched groups of women with type 2 diabetes and untreated subclinical hypothyroidism: patients with interferon-induced thyroiditis (n=8) and patients with Hashimoto's thyroiditis (n=12). Fasting plasma glucose, the homeostatic model assessment 1 of insulin resistance ratio (HOMA1-IR), glycated hemoglobin, the estimated glomerular filtration rate, as well as serum levels of thyrotropin, thyroid hormones, prolactin and insulin-like growth factor-1 (IGF-1) were assessed at baseline and after 4 months of metformin treatment. RESULTS: Apart from reducing plasma glucose, HOMA1-IR and glycated hemoglobin, metformin decreased serum levels of thyrotropin. Circulating levels of thyroid hormones, prolactin and IGF-1 remained at a similar level throughout the study. The effect of metformin on serum thyrotropin was stronger in patients with interferon-induced thyroiditis than in patients with Hashimoto's thyroiditis, as well as correlated with its impact on insulin sensitivity. CONCLUSIONS: Our results indicate that metformin may be an effective agent in patients with interferon-induced hypothyroidism. PMID- 26895276 TI - Basic and Meal Stimulated Plasma GIP Levels are Higher in Lean PCOS Women with FAI over 5. AB - OBJECTIVE: Glucose dependent insulinotropic peptide (GIP) belongs to the incretins which are responsible for 70% of the insulin release after oral glucose intake. Its impaired secretion was noted in several conditions involving insulin resistance, including polycystic ovary syndrome (PCOS), known as the state with increased testosterone level. This paper considers a possible relationship between the free androgen index (FAI) and basal as well as meal stimulated level of GIP in lean women affected by PCOS. To our knowledge, no previous study has evaluated the matter so far. DESIGN: cross-sectional study METHODS: 50 age matched lean women (BMI=20.76+/-1.83) were enrolled to the study and divided into 2 groups. Patients with phenotype with FAI<5 were classified as group 1, PCOS patients with FAI>5 formed group 2. All subjects underwent standard meal test. Serum GIP concentration was determined both at fasting and at 60 min of the test. Calculations were carried out using Statistica 10. RESULTS: Mann-Whitney test indicated a statistically significant difference in medians values of GIP plasma levels between groups on fasting (36.4 pg/ml vs. 59.6 pg/ml; p=0.0007) and at 60 min after meal test (50.1 pg/ml vs. 72.5 pg/ml; p=0.006). Spearman test indicated significant positive correlation between FAI and GIP levels at 0' and 60' in total study population (0':R=0.37;p=0.008; 60':R=0.28; p=0.049). CONCLUSION: Excess androgen activity might be a factor contributing to alter secretion of incretins in lean PCOS women. However it could not be ruled out that it is also possible that increased GIP levels might induce hyperandrogenemia in PCOS. An increased GIP levels may induce hyperinsulinemia and play an additive to insulin resistance role in progression to diabetes mellitus type 2 (DMT2). PMID- 26895277 TI - Use and Effectiveness of Continuous Subcutaneous Insulin Infusion (CSII) and Multiple Daily Insulin Injection Therapy (MIT) in Children, Adolescents and Young Adults with Type 1 Diabetes Mellitus. AB - Today continuous subcutaneous insulin infusion (CSII) is frequently used in children and adolescents with type 1 diabetes mellitus. The present cross sectional trial aimed to document current practice, quality of diabetes control and incidence of acute complications in different age-groups under CSII vs. multiple daily insulin injection therapy (MIT). Moreover the survey analyzed socio-demographic backgrounds of the patients. PATIENTS AND METHODS: A total of 901 patients (age 11.5+/-4.0, diabetes duration 4.0+/-3.6 years) was entered in the database. Clinical data, laboratory parameters and, using a standardized questionnaire, socio-demographic data were assessed. For age-related analyses patients were allocated to 4 groups: pre-school children (< 6 years), pre adolescents (>= 6 and<11 years), adolescents (>= 11 and<16 years) and young adults (>= 16 and<22 years). RESULTS: Of the cohort n=194 had a CSII, n=707 had a MIT. Patients with CSII vs. MIT had a longer diabetes duration, they used more frequently insulin analogues, performed more frequently blood-glucose self-tests and had a lower insulin dosage per kilogram body weight. In respect of HbA1c, the mean amplitude of blood-glucose excursions, but also of lipids, creatinine, microalbuminuria and blood pressure, there were no differences in neither age group between patients with CSII and MIT. In patients with CSII and MIT, there was a tendency (p<0.05) towards an increase in HbA1c in adolescents and young adults and there was a decrease (p<0.05 for tendency) in the frequency of hypoglycaemia from the age group of young adults to pre-school children. Adolescents and young adults with CSII had a higher educational level. Pre adolescents, adolescents and young adults with CSII have also better diabetes related knowledge. Moreover, in all age-groups, the parents of patients with CSII had mostly a lower unemployment rate and higher educational levels. CONCLUSIONS: The present analyses demonstrate that in all age-groups CSII provides convenient and flexible insulin delivery during routine treatment of type 1 diabetes. There is reasonable quality of diabetes control accompanied by a low incidence of hypoglycaemia and ketoacidosis. However, under CSII and MIT there is an increase of HbA1c towards adolescence. It must also highlighted that CSII seems to be expansive and that CSII is more frequently used in patients with better educational levels and deriving from higher social classes. PMID- 26895278 TI - Regional Disparities in Diabetes Care for Pediatric Patients with Type 1 Diabetes. A Cross-sectional DPV Multicenter Analysis of 24,928 German Children and Adolescents. AB - BACKGROUND: Data on regional differences in the quality of medical care in Germany are scarce. This study aimed to compare outcome quality and medical treatment of pediatric patients with type 1 diabetes between the federal states of Germany. METHODS: 24,928 patients (< 18 years of age) with type 1 diabetes and German residence were selected from the Diabetes-Patienten-Verlaufsdokumentation database. Indicators of outcome quality were HbA1C, overweight prevalence, and rate of severe hypoglycemia. To reflect medical treatment, use of insulin pumps and use of rapid-acting or long-acting insulin analogues were analyzed. Logistic regression models were created for binary variables with federal state as independent predictor. Linear regression was applied for HbA1C and Poisson regression for rate of severe hypoglycemia. Confounders: Sex, age, diabetes duration, migratory background. RESULTS: Disparity was observed for indicators of outcome quality between the 16 federal states of Germany (all p<0.05). After adjustment, HbA1C varied between 55.8 mmol/mol and 67.3 mmol/mol, overweight prevalence between 10.0 and 15.3%, severe hypoglycemia ranged from 0.06 events/PY to 0.21 events/PY. Overall, the best outcome quality appeared to be present in Saxony. Medical treatment also differed. The percentage of pediatrics on insulin pumps varied between 26.3 and 51.8%. The use of rapid-acting analogues ranged from 56.6 to 96.2% and the use of long-acting analogues varied between 41.9 and 96.9% (all p<0.0001). CONCLUSIONS: Medical treatment and outcome quality in pediatrics with type 1 diabetes differed within Germany. Disparities in individual socioeconomic status, regional deprivation, or differences in medical reimbursement decisions might have contributed to the patterns observed. PMID- 26895279 TI - Anionic, Cationic, and Nonionic Surfactants in Atmospheric Aerosols from the Baltic Coast at Asko, Sweden: Implications for Cloud Droplet Activation. AB - Recent analyses of atmospheric aerosols from different regions have demonstrated the ubiquitous presence of strong surfactants and evidenced surface tension values, sigma, below 40 mN m(-1), suspected to enhance the cloud-forming potential of these aerosols. In this work, this approach was further improved and combined with absolute concentration measurements of aerosol surfactants by colorimetric titration. This analysis was applied to PM2.5 aerosols collected at the Baltic station of Asko, Sweden, from July to October 2010. Strong surfactants were found in all the sampled aerosols, with sigma = (32-40) +/- 1 mN m(-1) and concentrations of at least 27 +/- 6 mM or 104 +/- 21 pmol m(-3). The absolute surface tension curves and critical micelle concentrations (CMC) determined for these aerosol surfactants show that (1) surfactants are concentrated enough in atmospheric particles to strongly depress the surface tension until activation, and (2) the surface tension does not follow the Szyszkowski equation during activation but is nearly constant and minimal, which provides new insights on cloud droplet activation. In addition, both the CMCs determined and the correlation (R(2) ~ 0.7) between aerosol surfactant concentrations and chlorophyll-a seawater concentrations suggest a marine and biological origin for these compounds. PMID- 26895280 TI - C-reactive protein: A differential biomarker for major depressive disorder and bipolar II disorder. AB - Objectives We aimed to examine whether the C-reactive protein (CRP) level could be used to differentiate between major depressive disorder (MDD) and bipolar II disorder (BD II). Methods Ninety-six healthy controls, 88 BD II and 72 MDD drug naive patients in their major depressive episodes were enrolled. The fasting plasma level of high-sensitivity CRP was assessed at baseline and after treatment. Results The BD II patients presented significantly higher 17-item Hamilton Depression Rating Scale (HDRS) scores and CRP levels at baseline when adjustment for age, gender, and body mass index (P < 0.001 and P < 0.001, respectively). After treatment the CRP levels remained significantly different (P < 0.001), although the HDRS score was not significantly different between the BD II and MDD patients. A receiver-operating characteristic analysis showed that a baseline CRP level of 621.6 ng/mL could discriminate between BD II and MDD, with an area under the curve of 0.816 and a sensitivity and specificity of 0.699 and 0.882, respectively. Furthermore, the baseline CRP level greater than 621.6 ng/ml had 28.2 higher odds of a diagnosis of BD II (P < 0.001, 95% confidence interval: 10.96-72.35). Conclusions The level of CRP plays a role of biomarker to differentiate between MDD and BD II depression in both their depressed and euthymic state. PMID- 26895281 TI - 'I have only little English': language anxiety of Filipino migrants with chronic disease. AB - OBJECTIVE: This study investigates communication challenges faced by Filipino patients with chronic diseases when engaging with healthcare professionals (HCPs). DESIGN: Nine focus groups were conducted between November 2010 and June 2011. RESULTS: Two main categories of themes were identified: patient-related and HCP-related factors. Patient-related factors included three subthemes: (1) lack of confidence in their English language abilities in clinical situations; (2) cultural attitudes; and (3) strategies used to improve communication. Older Filipinos with chronic disease were anxious about their lack of ability to explain their symptoms in English and were concerned that asking questions was conveying distrust in the HCPs. Most of the elderly simply nodded their head to indicate they understood even if they did not, for fear of being thought 'stupid'. Many participants preferred Filipino GPs or have a relative interpret for them. Two subthemes were related to HCPs including (1) not being listened to and (2) assumptions of understanding. HCPs were thought to assume English language skills in Filipino patients and therefore were not careful about ensuring understanding. CONCLUSIONS: These findings highlighted the need for HCPs to be more aware of 'grey areas' in English-language proficiency and the cultural lens through which migrants understand health. PMID- 26895283 TI - A Magnetically Responsive Polydiacetylene Precursor for Latent Fingerprint Analysis. AB - A magnetically responsive diacetylene (DA) powder was developed for the visualization of latent fingerprints. A mixture of the DA and magnetite nanoparticles, applied to a surface containing latent fingermarks, becomes immobilized along the ridge patterns of the fingerprints when a magnetic field is applied. Alignment along the ridge structures is a consequence of favorable hydrophobic interactions occurring between the long alkyl chains in the DAs and the lipid-rich, sebaceous latent fingermarks. UV irradiation of the DA-magnetite composite immobilized on the latent fingerprint results in the generation of blue colored PDAs. Heat treatment of the blue-colored image promotes a blue-to-red transition as well as fluorescence turn-on. A combination of the aligned pale brown-colored monomeric state, UV irradiation generated blue-colored PDA state, as well as the heat treatment generated red-colored and fluorescent PDA state enables efficient visual imaging of a latent fingerprint, which is deposited on various colored solid surfaces. PMID- 26895282 TI - Genomic comparison of Escherichia coli serotype O103:H2 isolates with and without verotoxin genes: implications for risk assessment of strains commonly found in ruminant reservoirs. AB - INTRODUCTION: Escherichia coli O103:H2 occurs as verotoxigenic E. coli (VTEC) carrying only vtx 1 or vtx 2 or both variants, but also as vtx-negative atypical enteropathogenic E. coli (aEPEC). The majority of E. coli O103:H2 identified from cases of human disease are caused by the VTEC form. If aEPEC strains frequently acquire verotoxin genes and become VTEC, they must be considered a significant public health concern. In this study, we have characterized and compared aEPEC and VTEC isolates of E. coli O103:H2 from Swedish cattle. METHODS: Fourteen isolates of E. coli O103:H2 with and without verotoxin genes were collected from samples of cattle feces taken during a nationwide cattle prevalence study 2011 2012. Isolates were sequenced with a 2*100 bp setup on a HiSeq2500 instrument producing >100* coverage per isolate. Single-nucleotide polymorphism (SNP) typing was performed using the genome analysis tool kit (GATK). Virulence genes and other regions of interest were detected. Susceptibility to transduction by two verotoxin-encoding phages was investigated for one representative aEPEC O103:H2 isolate. RESULTS AND DISCUSSION: This study shows that aEPEC O103:H2 is more commonly found (64%) than VTEC O103:H2 (36%) in the Swedish cattle reservoir. The only verotoxin gene variant identified was vtx 1a . Phylogenetic comparison by SNP analysis indicates that while certain subgroups of aEPEC and VTEC are closely related and have otherwise near identical virulence gene repertoires, they belong to separate lineages. This indicates that the uptake or loss of verotoxin genes is a rare event in the natural cattle environment of these bacteria. However, a representative of a VTEC-like aEPEC O103:H2 subgroup could be stably lysogenized by a vtx-encoding phage in vitro. PMID- 26895284 TI - A perspective on second medical indication patents in Brazil. PMID- 26895285 TI - Factors influencing nurses' perceptions of occupational safety. AB - To determine nurses' perceptions of occupational safety and their work environment and examine the sociodemographic traits and job characteristics that influence their occupational safety, we studied a sample of 278 nurses. According to the nurses, the quality of their work environment is average, and occupational safety is insufficient. In the subdimensions of the work environment scale, it was determined that the nurses think "labor force and other resources" are insufficient. In the occupational safety subdimensions "occupational illnesses and complaints" and "administrative support and approaches," they considered occupational safety to be insufficient. "Doctor-nurse-colleague relationships," "exposure to violence," and "work unit" (eg, internal medicine, surgical, intensive care) are the main factors that affect occupational safety. This study determined that hospital administrations should develop and immediately implement plans to ameliorate communication and clinical precautions and to reduce exposure to violence. PMID- 26895286 TI - Bimanual Coordination Learning with Different Augmented Feedback Modalities and Information Types. AB - Previous studies have shown that bimanual coordination learning is more resistant to the removal of augmented feedback when acquired with auditory than with visual channel. However, it is unclear whether this differential "guidance effect" between feedback modalities is due to enhanced sensorimotor integration via the non-dominant auditory channel or strengthened linkage to kinesthetic information under rhythmic input. The current study aimed to examine how modalities (visual vs. auditory) and information types (continuous visuospatial vs. discrete rhythmic) of concurrent augmented feedback influence bimanual coordination learning. Participants either learned a 90 degrees -out-of-phase pattern for three consecutive days with Lissajous feedback indicating the integrated position of both arms, or with visual or auditory rhythmic feedback reflecting the relative timing of the movement. The results showed diverse performance change after practice when the feedback was removed between Lissajous and the other two rhythmic groups, indicating that the guidance effect may be modulated by the type of information provided during practice. Moreover, significant performance improvement in the dual-task condition where the irregular rhythm counting task was applied as a secondary task also suggested that lower involvement of conscious control may result in better performance in bimanual coordination. PMID- 26895287 TI - Collimator optimization in myocardial perfusion SPECT using the ideal observer and realistic background variability for lesion detection and joint detection and localization tasks. AB - In SPECT imaging, collimators are a major factor limiting image quality and largely determine the noise and resolution of SPECT images. In this paper, we seek the collimator with the optimal tradeoff between image noise and resolution with respect to performance on two tasks related to myocardial perfusion SPECT: perfusion defect detection and joint detection and localization. We used the Ideal Observer (IO) operating on realistic background-known-statistically (BKS) and signal-known-exactly (SKE) data. The areas under the receiver operating characteristic (ROC) and localization ROC (LROC) curves (AUCd, AUCd+l), respectively, were used as the figures of merit for both tasks. We used a previously developed population of 54 phantoms based on the eXtended Cardiac Torso Phantom (XCAT) that included variations in gender, body size, heart size and subcutaneous adipose tissue level. For each phantom, organ uptakes were varied randomly based on distributions observed in patient data. We simulated perfusion defects at six different locations with extents and severities of 10% and 25%, respectively, which represented challenging but clinically relevant defects. The extent and severity are, respectively, the perfusion defect's fraction of the myocardial volume and reduction of uptake relative to the normal myocardium. Projection data were generated using an analytical projector that modeled attenuation, scatter, and collimator-detector response effects, a 9% energy resolution at 140 keV, and a 4 mm full-width at half maximum (FWHM) intrinsic spatial resolution. We investigated a family of eight parallel-hole collimators that spanned a large range of sensitivity-resolution tradeoffs. For each collimator and defect location, the IO test statistics were computed using a Markov Chain Monte Carlo (MCMC) method for an ensemble of 540 pairs of defect present and -absent images that included the aforementioned anatomical and uptake variability. Sets of test statistics were computed for both tasks and analyzed using ROC and LROC analysis methodologies. The results of this study suggest that collimators with somewhat poorer resolution and higher sensitivity than those of a typical low-energy high-resolution (LEHR) collimator were optimal for both defect detection and joint detection and localization tasks in myocardial perfusion SPECT for the range of defect sizes investigated. This study also indicates that optimizing instrumentation for a detection task may provide near optimal performance on the more challenging detection-localization task. PMID- 26895288 TI - Diagnostic and Therapeutic Implications of Histone Epigenetic Modulators in Breast Cancer. AB - Breast cancer is the most common cancer in women and great advancements have been made for individualised patient treatment. Through understanding the underlying altered biology in the different subtypes of breast cancer, targeted therapeutics have been developed. Unfortunately, resistance to targeted therapy, intrinsic or acquired, is a recurring theme in cancer treatment. Epigenetic-mediated resistance to targeted therapy has been identified across different types of cancer. In addition, tumorigenesis has also been linked to altered expression of epigenetic modifiers. Due to the reversible nature of epigenetic modifications, epigenetic proteins are appealing as therapeutic targets in both the primary and relapsed/resistant setting. In this review, we will discuss the current state of targetable epigenetic histone modifications and their diagnostic and therapeutic implications in breast cancer. PMID- 26895289 TI - Acute traumatic posterior fracture dislocation of the elbow in pediatric patients: impact of surgery time and associated fractures on outcome. AB - This study assessed the effect of the time interval from initial injury to surgery and the presence of associated fracture on functional outcomes after acute posterior elbow fracture dislocation. Twenty-six pediatric patients were evaluated with respect to operation time point (within 24 h vs. later) and associated fracture retrospectively. The Mayo Elbow Performance Index (MEPI) score was used to assess functional results. The MEPI score was 91 (80-100) in patients with one associated fracture and 83 (75-95) (P=0.02) in patients with more than one associated fracture. The MEPI score in patients treated within 24 h was 90.3 (75-95) and in those treated later than 24 h, it was 88.6 (75-100) (P=0.6). Treatment time (within 24 h vs. later) does not affect outcomes, but increasing numbers of associated injuries affect outcomes negatively. Level of study: Level IV case series. PMID- 26895290 TI - Distal femoral aspect ratios throughout childhood: an MRI study of normative data and sex comparisons. AB - The ratio of anteroposterior (AP) to medial-lateral (ML) dimensions of the distal femur in adults differs by sex. The average AP/ML dimension ratios are 0.82 for females and 0.79 for males. How and when this difference develops is not yet understood. In this study, the distal femoral dimensions and physeal development of 345 participants younger than 21 years of age were evaluated by MRI. Regression analysis indicated a significant increase in the AP/ML ratio with increasing age for both sexes. In girls, the ratio increased from 0.63 at ages 0 5 years to 0.76 at 15-20 years. In boys, the ratio increased from 0.61 to 0.73 over the same age groups. Female distal femur dimensions are narrower than that of males from birth. Throughout childhood, both sexes show gradual increases in AP/ML ratios. After closure of the physes, the AP/ML ratio in children approaches adult values, with females continuing to have relatively narrower dimensions than males. PMID- 26895291 TI - Hip pain is more frequent in severe hip displacement: a population-based study of 77 children with cerebral palsy. AB - The aim of this study was to assess whether hip pain was associated with radiographic hip displacement (migration percentage, MP) in a population-based cohort of children with cerebral palsy. Seventy-seven children, mean age 9.5 (SD 1.6) years and Gross Motor Function Classification System level III-V, were assessed. Caregivers responded to the Child Health Questionnaire pain questions and located recurrent pain on a body map. Hip pain was reported in 22 children (29%) and 27 hips (18%). Hip pain was significantly more frequent in hips with MP more than or equal to 50%, in children with spastic quadriplegia, and in those with Gross Motor Function Classification System level V. We conclude that severe hip displacement with MP more than or equal to 50% was associated with hip pain, whereas slight or moderate subluxation did not influence the occurrence of such pain. PMID- 26895292 TI - The effects of post-growth annealing on the structural and magnetic properties of BaFe2As2. AB - We investigate the effects of post-growth annealing on the structural and magnetic properties of BaFe2As2. Magnetic susceptibility measurements, which exhibit a signal corresponding to the magnetic phase transition, and high resolution x-ray diffraction measurements, which directly probe the structural order parameter, show that annealing causes the ordering temperatures of both the phase transitions to increase, sharpen and converge. In the as grown sample, our measurements show two distinct transitions corresponding to structural and magnetic ordering, which are separated in temperature by approximately 1 K. After 46 days (d) of annealing at 700 degrees C, the two become concurrent in temperature. These measurements demonstrate that the structural phase transition is second-order like when the magnetic and structural phase transitions are separated in temperature, and first-order like when the two phase transition temperatures coincide. This observation indicates that annealing causes the system to cross a hitherto undiscovered tricritical point. In addition, x-ray diffraction measurements show that the c-axis lattice parameter increases with annealing up to 30 d, but remains constant for longer annealing times. Comparisons of BaFe2As2 to SrFe2As2 are made when possible. PMID- 26895293 TI - Coarsened Exact Matching of Phaco-Trabectome to Trabectome in Phakic Patients: Lack of Additional Pressure Reduction from Phacoemulsification. AB - PURPOSE: To compare intraocular pressure (IOP) after trabectome-mediated ab interno trabeculectomy surgery in phakic patients (T) and trabectome with same session phacoemulsification (PT) using Coarsened Exact Matching. Although phacoemulsification is associated with IOP reduction when performed on its own, it is not known how much it contributes in PT. METHODS: Subjects were divided into phakic T and PT. Exclusion criteria were follow-up for <12 months and additional glaucoma surgery. Demographics were compared by the Mann-Whitney U test and chi-squared test for continuous and categorical variables, respectively. Multiple imputation was utilized to avoid eliminating data with missing values. Groups were then matched using Coarsened Exact Matching based on age, race, type of glaucoma, baseline IOP, and number of preoperative glaucoma medications. Univariate linear regression was used to examine IOP reduction after surgery; those variables that were statistically significant were included in the final multivariate regression model. RESULTS: A total of 753 cases were included (T: 255, PT: 498). When all variables except for age were kept constant, there was an additional IOP reduction of 0.05+/-0.01 mmHg conferred for every yearly increment in age. Every 1 mmHg increase in baseline IOP correlated to an additional IOP reduction of 0.80+/-0.02 mmHg. Phacoemulsification was not found to be a statistically significant contributor to IOP when comparing T and PT (p>=0.05). T had a 21% IOP reduction to 15.9+/-3.5 mmHg (p<0.01) while PT had an 18% reduction to 15.5+/-3.6 mmHg (p<0.01). Number of medications decreased (p<0.01) in both groups from 2.4+/-1.2 to 1.9+/-1.3 and from 2.3+/-1.1 to 1.7+/-1.3, respectively. CONCLUSION: Phacoemulsification does not make a significant contribution to postoperative IOP or number of medications when combined with trabectome surgery in phakic patients. PMID- 26895295 TI - Risk Factors for Stricture Formation After Esophageal Atresia Repair. AB - PURPOSE: Esophageal stricture remains a common morbidity of esophageal atresia (EA) repair. The purpose of this study was to examine the association of multiple pre- and postoperative variables with stricture formation after EA repair. METHODS: A retrospective review of all patients who underwent EA repair was performed from June 1999 to January 2014, excluding patients who died prior to discharge. Data were collected on patient demographics, disease specifics, treatment, and outcomes. A clinically significant esophageal stricture was defined as those requiring more than three esophageal dilations. Univariate analysis and multivariate analysis was performed to determine associations with stricture formation. RESULTS: The study included 121 infants. On univariate analysis, tracheoesophageal fistula (TEF) Gross classification (P = .046), method of repair (P = .0099), surgery staging (P = .0211), and development of leak (P = .0479) had a statistically significant association with stricture formation. Most (81%) underwent open repair with a stricture rate of 16.3%, while 20 patients underwent thoracoscopic repair with a 40% stricture rate. Multivariate analysis showed that patients undergoing a staged repair had increased risk of stricture formation over primary repair (odd ratio [OR] 6.360; P = .0008). Thoracoscopic surgery also increased the risk of stricture (OR 7.409; P = .0014). Cardiovascular anomalies were found to be associated with decreased stricture formation (OR 0.251; P = .0083). CONCLUSION: Thoracoscopic repair and staged repair were both associated with increased risk of clinically significant stricture formation after TEF repair. However, the presence of cardiovascular anomalies was associated with decreased stricture formation. TEF Gross classification also affects stricture risk. PMID- 26895294 TI - When to Monitor CD4 Cell Count and HIV RNA to Reduce Mortality and AIDS-Defining Illness in Virologically Suppressed HIV-Positive Persons on Antiretroviral Therapy in High-Income Countries: A Prospective Observational Study. AB - OBJECTIVE: To illustrate an approach to compare CD4 cell count and HIV-RNA monitoring strategies in HIV-positive individuals on antiretroviral therapy (ART). DESIGN: Prospective studies of HIV-positive individuals in Europe and the USA in the HIV-CAUSAL Collaboration and The Center for AIDS Research Network of Integrated Clinical Systems. METHODS: Antiretroviral-naive individuals who initiated ART and became virologically suppressed within 12 months were followed from the date of suppression. We compared 3 CD4 cell count and HIV-RNA monitoring strategies: once every (1) 3 +/- 1 months, (2) 6 +/- 1 months, and (3) 9-12 +/- 1 months. We used inverse-probability weighted models to compare these strategies with respect to clinical, immunologic, and virologic outcomes. RESULTS: In 39,029 eligible individuals, there were 265 deaths and 690 AIDS-defining illnesses or deaths. Compared with the 3-month strategy, the mortality hazard ratios (95% CIs) were 0.86 (0.42 to 1.78) for the 6 months and 0.82 (0.46 to 1.47) for the 9-12 month strategy. The respective 18-month risk ratios (95% CIs) of virologic failure (RNA >200) were 0.74 (0.46 to 1.19) and 2.35 (1.56 to 3.54) and 18-month mean CD4 differences (95% CIs) were -5.3 (-18.6 to 7.9) and -31.7 (-52.0 to 11.3). The estimates for the 2-year risk of AIDS-defining illness or death were similar across strategies. CONCLUSIONS: Our findings suggest that monitoring frequency of virologically suppressed individuals can be decreased from every 3 months to every 6, 9, or 12 months with respect to clinical outcomes. Because effects of different monitoring strategies could take years to materialize, longer follow-up is needed to fully evaluate this question. PMID- 26895296 TI - Validation and Assessment of Three Methods to Estimate 24-h Urinary Sodium Excretion from Spot Urine Samples in Chinese Adults. AB - 24-h urinary sodium excretion is the gold standard for evaluating dietary sodium intake, but it is often not feasible in large epidemiological studies due to high participant burden and cost. Three methods--Kawasaki, INTERSALT, and Tanaka--have been proposed to estimate 24-h urinary sodium excretion from a spot urine sample, but these methods have not been validated in the general Chinese population. This aim of this study was to assess the validity of three methods for estimating 24-h urinary sodium excretion using spot urine samples against measured 24-h urinary sodium excretion in a Chinese sample population. Data are from a substudy of the Prospective Urban Rural Epidemiology (PURE) study that enrolled 120 participants aged 35 to 70 years and collected their morning fasting urine and 24-h urine specimens. Bias calculations (estimated values minus measured values) and Bland Altman plots were used to assess the validity of the three estimation methods. 116 participants were included in the final analysis. Mean bias for the Kawasaki method was -740 mg/day (95% CI: -1219, 262 mg/day), and was the lowest among the three methods. Mean bias for the Tanaka method was -2305 mg/day (95% CI: -2735, 1875 mg/day). Mean bias for the INTERSALT method was -2797 mg/day (95% CI: -3245, 2349 mg/day), and was the highest of the three methods. Bland-Altman plots indicated that all three methods underestimated 24-h urinary sodium excretion. The Kawasaki, INTERSALT and Tanaka methods for estimation of 24-h urinary sodium excretion using spot urines all underestimated true 24-h urinary sodium excretion in this sample of Chinese adults. Among the three methods, the Kawasaki method was least biased, but was still relatively inaccurate. A more accurate method is needed to estimate the 24-h urinary sodium excretion from spot urine for assessment of dietary sodium intake in China. PMID- 26895297 TI - Monomethylated and unmethylated FUS exhibit increased binding to Transportin and distinguish FTLD-FUS from ALS-FUS. AB - Deposition of the nuclear DNA/RNA-binding protein Fused in sarcoma (FUS) in cytosolic inclusions is a common hallmark of some cases of frontotemporal lobar degeneration (FTLD-FUS) and amyotrophic lateral sclerosis (ALS-FUS). Whether both diseases also share common pathological mechanisms is currently unclear. Based on our previous finding that FUS deposits are hypomethylated in FTLD-FUS but not in ALS-FUS, we have now investigated whether genetic or pharmacological inactivation of Protein arginine methyltransferase 1 (PRMT1) activity results in unmethylated FUS or in alternatively methylated forms of FUS. To do so, we generated FUS specific monoclonal antibodies that specifically recognize unmethylated arginine (UMA), monomethylated arginine (MMA) or asymmetrically dimethylated arginine (ADMA). Loss of PRMT1 indeed not only results in an increase of UMA FUS and a decrease of ADMA FUS, but also in a significant increase of MMA FUS. Compared to ADMA FUS, UMA and MMA FUS exhibit much higher binding affinities to Transportin 1, the nuclear import receptor of FUS, as measured by pull-down assays and isothermal titration calorimetry. Moreover, we show that MMA FUS occurs exclusively in FTLD-FUS, but not in ALS-FUS. Our findings therefore provide additional evidence that FTLD-FUS and ALS-FUS are caused by distinct disease mechanisms although both share FUS deposits as a common denominator. PMID- 26895298 TI - High aortic pulse-wave velocity may be responsible for elevated red blood cell distribution width in overweight and obese people: a community-based, cross sectional study. AB - BACKGROUND: Obesity and overweight are risk factors for atherosclerosis. Red blood cell distribution width (RDW) is associated with subclinical cardiac diseases. The aim of this study was to investigate the association between RDW and aortic stiffness in overweight or obese subjects. METHODS: A total of 101 overweight or obese subjects without overt cardiovascular disorders, and 48 healthy controls were enrolled. RDW, aortic pulse-wave velocity (PWV) and augmentation index 75 (Aix75) were evaluated. The case subjects were divided into two sub-groups according to PWV values; >= 10 m/s in group I, and < 10 m/s in group II. Bivariate correlation and multiple regression analyses (stepwise) were performed. RESULTS: RDW and PWV were considerably increased in the case groups compared with the controls. RDW was significantly increased in group I compared with group II and the controls [median 12.0 m/s, interquartile range (IQR): 10.5 17.5; median 11.7 m/s, IQR: 10.2-14.2, and median 11.4 m/s, IQR: 9.6-15.5, p < 0.05, respectively]. Resting heart rate and age were higher in group I than group II (81 +/- 11 vs 74 +/- 12 beats/min and 41 +/- 120 vs 36 +/- 9 years, respectively, p < 0.05). Regression analyses revealed that while log-RDW, age and resting heart rate were independent predictors for aortic PWV, log-RDW was the most important predictor in the final model. CONCLUSIONS: RDW, resting heart rate and age independently predicted arterial stiffness, and RDW may be useful to provide an early recognition of subclinical atherosclerosis in overweight and obese individuals. PMID- 26895299 TI - The impact of expectant management, systemic methotrexate and surgery on subsequent pregnancy outcomes in tubal ectopic pregnancy. AB - BACKGROUND: The most common treatment modalities of ectopic pregnancy may influence long-term subsequent fertility outcomes in women who previously treated for ectopic pregnancy. AIMS: Our objective was to compare long-term subsequent fertility outcomes after treatment with expectant management, systemic methotrexate (MTX) and surgery in tubal ectopic pregnancy. METHODS: We searched our database for all women diagnosed with tubal ectopic pregnancy between January 2007 and January 2011 who were managed expectantly, with systemic MTX and with surgery. Treatment success and spontaneous pregnancy rates were compared in patients who desire to conceive following a tubal pregnancy. RESULTS: One hundred twelve of 151 women desired to conceive following tubal ectopic pregnancy. Twenty seven of 112 (24.1 %) patients were managed expectantly. Fifty-three (47.3 %) and 32 (28.5 %) patients were managed with systemic MTX or surgery, respectively. All patients in expectant and surgery groups were managed successfully. Two (3.7 %) patients had surgery after failed treatment with systemic MTX. Spontaneous intrauterine pregnancy rates were 62.9 % in expectantly managed women, 58.4 % in women with systemic MTX and 68.7 % in women with surgery (p > 0.05). CONCLUSIONS: Treatment of ectopic pregnancy with either expectant management or systemic MTX is equally effective as compared to surgery. Spontaneous intrauterine pregnancy rates were comparable in expectant management, systemic methotrexate and surgery. PMID- 26895300 TI - Cardiac arrest secondary to acute coronary syndrome: a 4-year observational study of patient characteristics and outcomes. AB - BACKGROUND: Cardiac arrest due to ischaemia is frequently the first manifestation of cardiovascular disease. We sought to describe the characteristics and outcomes of patients admitted to the Intensive Care Unit (ICU) with a diagnosis of cardiac arrest secondary to acute coronary syndrome (ACS). METHODS: We performed a retrospective analysis of patients admitted to the intensive care unit over a 4 year period. Baseline demographic characteristics, the use of therapeutic hypothermia, rates of percutaneous coronary intervention, co-morbidities and baseline left ventricular function were all documented. Outcomes included Glasgow Coma Scale (GCS) at time of discharge from the ICU, survival to hospital discharge, 6 months survival and left ventricular function at 6 months. RESULTS: We identified 31 admissions to the ICU following cardiac arrest due to ACS during the study period. 71 % of patients survived to hospital discharge and all of these were still alive at 6 months. 65 % had good neurological function (GCS > 13) when discharged from ICU. Mean left ventricular ejection fraction remained stable at 6 months. CONCLUSIONS: A significant proportion of patients admitted to the intensive care unit with a diagnosis of cardiac arrest secondary to acute coronary syndrome survive to hospital discharge with meaningful recovery in neurological and cardiac function. PMID- 26895302 TI - Monodisperse Dual-Functional Upconversion Nanoparticles Enabled Near-Infrared Organolead Halide Perovskite Solar Cells. AB - Extending the spectral absorption of organolead halide perovskite solar cells from visible into near-infrared (NIR) range renders the minimization of non absorption loss of solar photons with improved energy alignment. Herein, we report on, for the first time, a viable strategy of capitalizing on judiciously synthesized monodisperse NaYF4 :Yb/Er upconversion nanoparticles (UCNPs) as the mesoporous electrode for CH3 NH3 PbI3 perovskite solar cells and more importantly confer perovskite solar cells to be operative under NIR light. Uniform NaYF4 :Yb/Er UCNPs are first crafted by employing rationally designed double hydrophilic star-like poly(acrylic acid)-block-poly(ethylene oxide) (PAA-b-PEO) diblock copolymer as nanoreactor, imparting the solubility of UCNPs and the tunability of film porosity during the manufacturing process. The subsequent incorporation of NaYF4 :Yb/Er UCNPs as the mesoporous electrode led to a high efficiency of 17.8 %, which was further increased to 18.1 % upon NIR irradiation. The in situ integration of upconversion materials as functional components of perovskite solar cells offers the expanded flexibility for engineering the device architecture and broadening the solar spectral use. PMID- 26895301 TI - HIV-Tat Induces the Nrf2/ARE Pathway through NMDA Receptor-Elicited Spermine Oxidase Activation in Human Neuroblastoma Cells. AB - Previously, we reported that HIV-Tat elicits spermine oxidase (SMO) activity upregulation through NMDA receptor (NMDAR) stimulation in human SH-SY5Y neuroblastoma cells, thus increasing ROS generation, which in turn leads to GSH depletion, oxidative stress, and reduced cell viability. In several cell types, ROS can trigger an antioxidant cell response through the transcriptional induction of oxidative stress-responsive genes regulated by the nuclear factor erythroid 2-related factor 2 (Nrf2). Here, we demonstrate that Tat induces both antioxidant gene expression and Nrf2 activation in SH-SY5Y cells, mediated by SMO activity. Furthermore, NMDAR is involved in Tat-induced Nrf2 activation. These findings suggest that the NMDAR/SMO/Nrf2 pathway is an important target for protection against HIV-associated neurocognitive disorders. PMID- 26895303 TI - Evaluation of day-by-day variability of home blood pressure using a home blood pressure telemonitoring system. AB - BACKGROUND: There have been no reports indicating how a home blood pressure (HBP) telemonitoring system influences day-by-day HBP variability. METHODS: We evaluated day-by-day HBP variability using an HBP telemonitoring system, randomizing 60 individuals to either a telemonitoring group or the control group. RESULTS: There were no significant changes in day-by-day HBP variability between the two groups. However, the SD, root mean sum square differences, and the average real variability values for systolic blood pressure only in the control group in the latter half of the 4-week study were significantly greater than those in the first half (P<0.05). CONCLUSION: A HBP telemonitoring system could be useful in obtaining stable HBP readings over a certain period of time. PMID- 26895304 TI - Prevalence of hypertension in a sample of schoolchildren in the Belgrade district. AB - OBJECTIVE: The aim of this study was to estimate the prevalence of hypertension in a sample of schoolchildren in the district of Vozdovac (Belgrade). METHODS: This study included 780 pupils from I, III, V and VII classes of a primary school and I and III classes of a high school in the district of Vozdovac (Belgrade). The anthropometric data were obtained from medical records of a regular health survey in 2014-2015. Blood pressure (BP) was measured three times using a mercury sphygmomanometer with a cuff of appropriate size at a 5 min interval. BP values at or above the 95th percentile for age, sex, and height were considered indicative of hypertension. Statistical analysis included descriptive statistics, chi-test, t-test, and correlation analysis. RESULTS: Of the participating students, 15.0% were overweight and 6.7% were obese. A significant negative correlation was observed between BMI categories and age (rho=-0.126; P<0.01). The average systolic blood pressure values in boys and girls were 105.0+/-14.1 (range 80.0-150.0) and 102.5+/-12.3 (range 80-155) mmHg, respectively. The average diastolic blood pressure values in boys and girls were 67.6+/-8.8 (range 50-100) and 66.2+/-7.7 (range 50-95) mmHg, respectively. The prevalence of hypertension was 10.5%. A significant positive association was found between the presence of hypertension and age (rho=0.150, P<0.01) and higher BMI level (rho=0.115, P<0.01). CONCLUSION: In our sample of schoolchildren, a high prevalence of hypertension was found. Moreover, elevated BP values correlated strongly with age and BMI. PMID- 26895305 TI - MicroRNA-939 down-regulates CD2-associated protein by targeting promoter in HEK 293T cells. AB - CD2-associated protein (CD2AP) serves as a slit diaphragm (SD) protein and plays essential roles in maintaining podocyte integrity and reducing proteinuria. MicroRNAs (miRNAs) are novel regulators of gene expression. Podocyte-specific loss of miRNAs would lead to significant proteinuria. Here, we report new evidence in which miRNAs may function to suppress CD2AP expression through a transcriptional way. By scanning human CD2AP promoter in silico for sequences complementary to known miRNAs, we chose miR-939, miR-148b*, miR-191*, miR-638 as four candidates and transfected them into HEK-293T cells. Dual-luciferase reporter assay identified that only miR-939 significantly reduced the relative luciferase activity of CD2AP promoter region. Further analysis confirmed that the mRNA and protein expressions of CD2AP were also down-regulated by miR-939. In conclusion, we have identified that miR-939 targets CD2AP promoter sequences and suppresses its gene expression. These findings suggest that miRNAs may mediate podocyte injury via reducing the expression of the SD proteins, such as CD2AP. PMID- 26895306 TI - A stochastic model of carbon nanotube deposition in the airways and alveoli of the human respiratory tract. AB - CONTEXT: In the past two decades, possible exposure of workers to nanoparticles has excited the attention of occupational medicine, resulting in the conception of related risk assessments. Although most nanoparticles have been categorized as hazardous substances in the meantime, their behavior in the human respiratory tract still bears some enigmas, which require clarification. OBJECTIVES: The study pursues the goal to provide detailed theoretical lung deposition data of carbon nanotubes (CNT) with various diameters and lengths. Besides a quantification of total and regional deposition, also airway generation-specific deposition has been subjected to the modeling process. METHODS: Theoretical approach of CNT deposition in the human lungs has been conducted by assuming a stochastic structure of the bronchial network, within which particle transport takes place along randomly selected paths. Fluid-dynamic particle characteristics have been simulated by application of a rigid fiber model, which considers diverse forces and torques acting on the particles during their translocation within the inhaled air. Particle deposition in the entire lungs has been approximated by using the aerodynamic/thermodynamic diameter concept and related empirical deposition formulae. RESULTS: Theoretical deposition data reflect a significant dependence of CNT deposition on (a) the effective size of the particles and (b) the conditions, under which they are taken up into the respiratory tract. Extremely small CNT (~1 nm) are primarily filtered in the extrathoracic airways, intermediately sized CNT (~10 nm) exhibit a preference to deposit in the alveoli, and large CNT (~100 nm) are marked by minimum deposition. CONCLUSION: Pulmonary deposition of CNT is subject to a partly remarkable variation. According to the model of this study, particles of intermediate size seem to bear highest potential to act as hazardous substances. PMID- 26895307 TI - Changes in HPBMC markers of immmune function following controlled short-term inhalation exposures of humans to hardwood smoke. AB - Previous studies have shown that complex mixtures containing particulate matter (PM) and polycyclic aromatic hydrocarbons (PAHs) produce systemic immunotoxicity in animal models following inhalation exposures. While we and others have shown that emissions associated with hardwood smoke (HWS), cigarette smoke and diesel exhaust can suppress the immune systems of animals in vitro and in vivo, there have been few immune function studies on human peripheral blood mononuclear cells (HPBMC) following exposure of humans to HWS. Our work shows that T cells are an important targets of PM and PAH immunotoxicity. These studies were conducted on HPBMC from 14 human volunteers receiving four 2 h nightly exposures to clean air or HWS at a concentration of 500 ug/m(3). We measured anti-CD3/anti-CD28 stimulated T-cell proliferation and HPBMC cytokine production in cell supernatants, including interleukin 1beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), interleukin 8 (IL-8), TH1 cytokines gammaIFN and IL-2, TH2 cytokine IL-4, Th17 cytokine interleukin 17A (IL-17A) and interleukin 10 (IL-10). We analyzed results using analysis of variance (ANOVA), t tests and Pearson correlation. Results showed that there was significant variation in the amount of T-cell proliferation observed following polyclonal activation with anti-CD3/anti-CD28 antibodies in both the air and HWS-exposed groups. There was not a significant effect of HWS on T-cell proliferation. However, we did find a strong relationship between the presence of proinflammatory cytokines (IL-1beta, TNF-alpha, IL-6, but not IL-8) and the amount of T-cell proliferation seen in individual donors, demonstrating that brief exposures of humans to HWS can produce changes in systemic immunity that is associated with proinflammatory cytokines. PMID- 26895308 TI - Development of a Zealand white rabbit deposition model to study inhalation anthrax. AB - Despite using rabbits in several inhalation exposure experiments to study diseases such as anthrax, there is a lack of understanding regarding deposition characteristics and fate of inhaled particles (bio-aerosols and viruses) in the respiratory tracts of rabbits. Such information allows dosimetric extrapolation to humans to inform human outcomes. The lung geometry of the New Zealand white rabbit (referred to simply as rabbits throughout the article) was constructed using recently acquired scanned images of the conducting airways of rabbits and available information on its acinar region. In addition, functional relationships were developed for the lung and breathing parameters of rabbits as a function of body weight. The lung geometry and breathing parameters were used to extend the existing deposition model for humans and several other species to rabbits. Evaluation of the deposition model for rabbits was made by comparing predictions with available measurements in the literature. Deposition predictions in the lungs of rabbits indicated smaller deposition fractions compared to those found in humans across various particle diameter ranges. The application of the deposition model for rabbits was demonstrated by extrapolating deposition predictions in rabbits to find equivalent human exposure concentrations assuming the same dose-response relationship between the two species. Human equivalent exposure concentration levels were found to be much smaller than those for rabbits. PMID- 26895309 TI - Sudden death following endomyocardial biopsy of cardiac metastasis from malignant melanoma. PMID- 26895310 TI - Revisiting the Valence and Conduction Band Size Dependence of PbS Quantum Dot Thin Films. AB - We use a high signal-to-noise X-ray photoelectron spectrum of bulk PbS, GW calculations, and a model assuming parabolic bands to unravel the various X-ray and ultraviolet photoelectron spectral features of bulk PbS as well as determine how to best analyze the valence band region of PbS quantum dot (QD) films. X-ray and ultraviolet photoelectron spectroscopy (XPS and UPS) are commonly used to probe the difference between the Fermi level and valence band maximum (VBM) for crystalline and thin-film semiconductors. However, we find that when the standard XPS/UPS analysis is used for PbS, the results are often unrealistic due to the low density of states at the VBM. Instead, a parabolic band model is used to determine the VBM for the PbS QD films, which is based on the bulk PbS experimental spectrum and bulk GW calculations. Our analysis highlights the breakdown of the Brillioun zone representation of the band diagram for large band gap, highly quantum confined PbS QDs. We have also determined that in 1,2 ethanedithiol-treated PbS QD films the Fermi level position is dependent on the QD size; specifically, the smallest band gap QD films have the Fermi level near the conduction band minimum and the Fermi level moves away from the conduction band for larger band gap PbS QD films. This change in the Fermi level within the QD band gap could be due to changes in the Pb:S ratio. In addition, we use inverse photoelectron spectroscopy to measure the conduction band region, which has similar challenges in the analysis of PbS QD films due to a low density of states near the conduction band minimum. PMID- 26895311 TI - Trinucleotide repeat length in the first exon of the androgen receptor gene may be associated with prostate carcinogenesis and facilitate prediction of prostate cancer aggressiveness. PMID- 26895312 TI - Functional crosstalk between membrane lipids and TLR biology. AB - Toll-like receptors (TLRs) are important transmembrane proteins of the innate immune system that detect invading pathogens and subsequently orchestrate an immune response. The ensuing inflammatory processes are connected to lipid metabolism at multiple levels. Here, we describe different aspects of how membrane lipids can shape the response of TLRs. Recent reports have uncovered the role of individual lipid species on membrane protein function and mouse models have contributed to the understanding of how changes in lipid metabolism alter TLR signaling, endocytosis, and cytokine secretion. Finally, we discuss the importance of systematic approaches to identify the function of individual lipid species or the composition of membrane lipids in TLR-related processes. PMID- 26895313 TI - Prenatal Exposure to Perfluorocarboxylic Acids (PFCAs) and Fetal and Postnatal Growth in the Taiwan Maternal and Infant Cohort Study. AB - BACKGROUND: Perfluorocarboxylic acids (PFCAs) are environmentally and biologically persistent synthetic chemicals. PFCAs include perfluorooctanoic acid (PFOA; C8) and long-chain PFCAs (C9-C20). Studies examining long-chain PFCAs and fetal and postnatal growth are limited. OBJECTIVES: We investigated the associations of prenatal exposure to long-chain PFCAs with fetal and postnatal growth. METHODS: For 223 Taiwanese mothers and their term infants, we measured PFOA and four long-chain PFCAs (ng/mL) in third-trimester maternal serum; infant weight (kg), length and head circumference (cm) at birth; and childhood weight and height at approximately 2, 5, 8, and 11 years of age. For each sex, we used multivariable linear regression to examine associations between ln-transformed prenatal PFCAs and continuous infant measures, and logistic regression to examine small for gestational age (SGA). Linear mixed models were applied to prenatal PFCAs and childhood weight and height z-scores. RESULTS: In girls, prenatal perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDeA), perfluoroundecanoic acid (PFUnDA), and perfluorododecanoic acid (PFDoDA) concentrations were inversely associated with birth weight [e.g., betabirth weight (kg) = -0.06, 95% CI: -0.11, -0.01 per 1 ln-unit PFUnDA increase]; prenatal PFDeA and PFUnDA were associated with elevated odds of SGA; and PFDeA, PFUnDA, and PFDoDA were associated with lower average childhood height z-score. In boys, prenatal PFNA, and PFDoDA were associated with reductions in height at certain ages in childhood, but not with size at birth. CONCLUSIONS: Prenatal exposure to long-chain PFCAs may interfere with fetal and childhood growth in girls, and childhood growth in boys. Citation: Wang Y, Adgent M, Su PH, Chen HY, Chen PC, Hsiung CA, Wang SL. 2016. Prenatal exposure to perfluorocarboxylic acids (PFCAs) and fetal and postnatal growth in the Taiwan Maternal and Infant Cohort Study. Environ Health Perspect 124:1794-1800; http://dx.doi.org/10.1289/ehp.1509998. PMID- 26895314 TI - Development of the World Health Organization Measles Programmatic Risk Assessment Tool Using Experience from the 2009 Measles Outbreak in Namibia. AB - In the World Health Organization (WHO) African region, reported measles cases decreased by 80% and measles mortality declined by 88% during 2000-2012. Based on current performance trends, however, focused efforts will be needed to achieve the regional measles elimination goal. To prioritize efforts to strengthen implementation of elimination strategies, the Centers for Disease Control and Prevention and WHO developed a measles programmatic risk assessment tool to identify high-risk districts and guide and strengthen program activities at the subnational level. This article provides a description of pilot testing of the tool in Namibia using comparisons of high-risk districts identified using 2006 2008 data with reported measles cases and incidence during the 2009 outbreak. Of the 34 health districts in Namibia, 11 (32%) were classified as high risk or very high risk, including the district of Engela where the outbreak began in 2009. The district of Windhoek, including the capital city of Windhoek, had the highest overall risk score-driven primarily by poor population immunity and immunization program performance-and one of the highest incidences during the outbreak. Other high-risk districts were either around the capital district or in the northern part of the country near the border with Angola. Districts categorized as high or very high risk based on the 2006-2008 data generally experienced high measles incidence during the large outbreak in 2009, as did several medium- or low-risk districts. The tool can be used to guide measles elimination strategies and to identify programmatic areas that require strengthening. PMID- 26895315 TI - Influence of Molecular Structure on O2-Binding Properties and Blood Circulation of Hemoglobin-Albumin Clusters. AB - A hemoglobin wrapped covalently by three human serum albumins, a Hb-HSA3 cluster, is an artificial O2-carrier with the potential to function as a red blood cell substitute. This paper describes the synthesis and O2-binding properties of new hemoglobin-albumin clusters (i) bearing four HSA units at the periphery (Hb-HSA4, large-size variant) and (ii) containing an intramolecularly crosslinked Hb in the center (XLHb-HSA3, high O2-affinity variant). Dynamic light scattering measurements revealed that the Hb-HSA4 diameter is greater than that of either Hb HSA3 or XLHb-HSA3. The XLHb-HSA3 showed moderately high O2-affinity compared to the others because of the chemical linkage between the Cys-93(beta) residues in Hb. Furthermore, the blood circulation behavior of 125I-labeled clusters was investigated by assay of blood retention and tissue distribution after intravenous administration into anesthetized rats. The XLHb-HSA3 was metabolized faster than Hb-HSA3 and Hb-HSA4. Results suggest that the molecular structure of the protein cluster is a factor that can influence in vivo circulation behavior. PMID- 26895316 TI - [Secondary retroperitoneal fibrosis in a 39-year-old man after rectal cancer]. AB - A 39-year-old man had been treated for rectal cancer 6 years ago by lower anterior resection of the rectum and perioperative radiochemotherapy. Since then follow-up had been unremarkable but now the patient presented with unspecific lower abdominal pain. The cause of the pain was identified as paraneoplastic retroperitoneal fibrosis secondary to metachronous pulmonary metastases of the rectal cancer. PMID- 26895317 TI - DNA-Binding, Photocleavage, and Photodynamic Anti-cancer Activities of Pyridyl Corroles. AB - The DNA-binding, photocleavage, and antitumor activity of three free base pyridyl corroles 1, 2, and 3 have been investigated. The binding affinity toward CT-DNA decreases with increasing number of pentafluorophenyl, whereas the photocleavage activity toward pBR322 DNA becomes more efficient. Singlet oxygen was demonstrated as active species responsible for DNA cleavage. These corroles exhibited high cytotoxicity against three tested cancer cells (Hela, HapG2, and A549) and the cytotoxicity could be further enhanced under irradiation. Intracellular reactive oxygen species level was also monitored using HeLa Cells upon the combined treatment of corroles and light. These corroles could be absorbed by HeLa cells at low concentration. They can induce the decrease of mitochondrial membrane potential and apoptosis of tumor cells under irradiation. PMID- 26895318 TI - Role of cardiac TBX20 in dilated cardiomyopathy. AB - Dilated cardiomyopathy (DCM) is an important cause of heart failure and sudden cardiac death worldwide. Transcription factor TBX20 has been shown to play a crucial role in cardiac development and maintenance of adult mouse heart. Recent studies suggest that TBX20 may have a role in pathophysiology of DCM. In the present study, we examined TBX20 expression in idiopathic DCM patients and in an animal model of cardiomyopathy, and studied its correlation with echocardiographic indices of LV function. Endomyocardial biopsies (EMBs) from intraventricular septal from the right ventricle region were obtained from idiopathic DCM patients (IDCM, n = 30) and from patients with ventricular septal defect (VSD, n = 14) with normal LVEF who served as controls. An animal model of DCM was developed by right renal artery ligation in Wistar rats. Cardiac TBX20 mRNA levels were measured by real-time PCR in IDCM, controls, and in rats. The role of DNA promoter methylation and copy number variation (CNVs) in regulating TBX20 gene expression was also investigated. Cardiac TBX20 mRNA levels were significantly increased (8.9 fold, p < 0.001) in IDCM patients and in RAL rats as compared to the control group. Cardiac TBX20 expression showed a negative correlation with LVEF (r = -0.71, p < 0.001) and a positive correlation with left ventricular end-systolic volume (r = 0.39, p = 0.038). No significant difference in TBX20 CNVs and promoter methylation was observed between IDCM patients and control group. Our results suggest a potential role of TBX20 in pathophysiology of DCM. PMID- 26895319 TI - Advanced glycation end products (AGEs) and its receptors in the pathogenesis of hyperthyroidism. AB - Oxidative stress has been implicated in the pathogenesis of hyperthyroidism and its complications. Interaction of advanced glycation end products (AGEs) with receptor RAGE (receptor for AGEs) generates reactive oxygen species. Soluble receptor for AGEs (sRAGE) competes with RAGE for binding with AGEs and attenuates the generation of ROS. Low levels sRAGE and high levels AGEs would generate more ROS leading to hyperthyroidism and its complications. The objectives are to determine if levels of serum sRAGE are low and the levels of AGEs and AGEs/sRAGE are high in patients with hyperthyroidism. The study subjects comprised of 33 patients with hyperthyroidism and 20 controls. Levels of serum sRAGE were lower, while that of AGEs and AGEs/sRAGE were higher in patients compared to controls, being significant only for sRAGE and AGEs/sRAGE. When the levels of sRAGE, AGEs, and AGEs/sRAGE were assessed for hyperthyroidism associated with different diseases, the levels of sRAGE were lower in Hashimoto disease, and levels of AGEs were higher in patients with Graves' disease compared to control. The levels of AGEs/sRAGE were elevated in an all except patients with Hashimoto disease. The levels of AGEs, sRAGE, or AGEs/RAGE were not correlated with age, weight, and blood pressures except systolic pressure which was inversely correlated with sRAGE. The levels of sRAGE were negatively correlated with AGEs and AGEs/sRAGE. The levels of AGEs/sRAGE were positively correlated with AGEs. In conclusion, low levels of sRAGE, and high levels of AGEs and AGEs/sRAGE are risk biomarkers in the pathogenesis hyperthyroidism and its complications. PMID- 26895320 TI - Effect of GTP-binding protein (YPT1 protein) on the enhanced yeast vacuolar activity. AB - Yeast GTP-binding protein (YPT1 protein) has been reported to function in the early stages of the secretory pathway. Particularly, YPT1 protein is observed to regulate both the endoplasmic reticulum-to-Golgi transport and the autophagy. Therefore, the YPT1 protein overexpressed in yeast vacuoles is expected to enhance antimicrobial and anticancer activity. The enhancement of yeast vacuolar activity under the overexpression of YPT1 was evaluated by the analysis of lysozyme activity, antimicrobial activity against Escherichia coli and Staphylococcus aureus, and MTT assay against HeLa cell lines. Additionally, the rise in concentration of some important proteinases inside the vacuole, such as proteinase A, proteinase B, and vacuolar carboxypeptidase Y (CPY) were also recorded using a 2DE technique. All results imply YPT1 involvement in the recruitment of some specific proteinases into vacuoles, which leads to the enhancement of vacuolar activity. Since these there proteinases belong to the CPY pathway, YPT1 is even believed to up-regulate this trafficking pathway in yeast cells. Future studies, however, should be carried out to discover the mechanisms that allow YPT1 to recruit these proteins into yeast vacuoles. PMID- 26895321 TI - Cerebral hyperperfusion syndrome after internal carotid artery dissection with persistent occlusion. PMID- 26895322 TI - Neurological injuries and extracorporeal membrane oxygenation: the challenge of the new ECMO era. AB - Extracorporeal membrane oxygenation (ECMO) is a life-saving mechanical respiratory and/or circulatory support for potentially reversible severe heart or respiratory injury untreatable with conventional therapies. Thanks to the technical and management improvements the use of ECMO has increased dramatically in the last few years. Data in the literature show a progressive increase in the overall outcome. Considering the improving survival rate of patients on ECMO, and the catastrophic effect of neurological injuries in such patients, the topic of neurological damage during the ICU stay in ECMO is gaining importance. We present a case series of six neurological injuries that occurred in 1 year during the ECMO run or after the ECMO weaning. In each case the neurological complication had a dramatic effect: ranging from brain death to prolonged ICU stay and long term disability. This case series has an informative impact for the multidisciplinary teams treating ECMO patients because of its heterogeneity in pathogenesis and clinical manifestation: cerebral hemorrhage, ischemic stroke due to cerebral fat embolism, acute disseminated encephalomyelitis due to H1N1 Influenza. In our ECMO hub we started strict neurological monitoring involving intensivists, a neurologist and our radiology service, but neurological complications are still an insidious diagnosis and treatment. Considering several possible neurological injuries may help reduce delay in diagnosis and speed rehabilitation. PMID- 26895324 TI - Erratum to: A nomogram based on mammary ductoscopic indicators for evaluating the risk of breast cancer in intraductal neoplasms with nipple discharge. PMID- 26895323 TI - Use of herbal remedies by multiple sclerosis patients: a nation-wide survey in Italy. AB - Though recent progress in multiple sclerosis (MS) treatment is remarkable, numerous unmet needs remain to be addressed often inducing patients to look for complementary and alternative medicines (CAM), especially herbal remedies (HR). HR use, scarcely investigated in MS, may cause adverse reactions (AR) and interfere with conventional treatment. We performed a survey aimed at evaluating use and attitudes towards HR and factor associated to HR use. Other CAM use and attitudes have been investigated as well. Multiple-choice questionnaires were distributed to MS out patients attending 14 Italian referral Centers. Multivariable logistic regression was used to identify HR use determinants. Present/past HR use for either MS or other diseases was reported in 35.6 % of 2419 cases (95 % CI 36.0-40.0 %). CAM use was reported in 42.5 % of cases. Independent predictors of HR use were represented by higher education, geographic area, dissatisfaction with conventional treatment of diseases other than MS and benefit perception from CAM use. Both HR and CAM use were not always disclosed to the healthcare professional. In conclusion, HR and other CAM appear to be popular among MS patients. The involvement of the healthcare professionals appears to be scarce with potential risk of AR or interference with conventional treatments. PMID- 26895325 TI - HER2 FISH classification of equivocal HER2 IHC breast cancers with use of the 2013 ASCO/CAP practice guideline. AB - The status of human epidermal growth factor receptor 2 (HER2, ERBB2) determines the eligibility of breast cancer patients to receive HER2-targeted therapy. The majority of HER2 testing in the U.S. is performed using a combination of immunohistochemistry (IHC) screening followed by fluorescence in situ hybridization (FISH) for IHC equivocal cases. In 2013, the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) updated the guideline for HER2 testing. This study evaluates the impact of the 2013 ASCO/CAP updated guideline on final HER2 FISH classification of breast cancers with an equivocal IHC result. For each case, we reported a FISH result according to the 2013 updated guideline and recorded a separated result using the 2007 guideline for investigational purpose. McNemar's test and Bowker's symmetry test were used to compare the classifications by the two guidelines. Among 172 HER2 IHC 2+ equivocal cases, use of the 2103 guideline changed classifications in 36 cases (21 %) when compared with the results expected by use of the 2007 guideline, and yielded a higher proportion of positive (28.5 vs. 23.3 %) and equivocal (16.3 vs. 4.1 %), and a lower proportion of negative (55.2 vs. 72.7 %) cases (p < 0.001). The major classification change with use of the updated guideline is from the HER2 FISH negative to equivocal in 26 cases (15 %). Our study has shown that implementation of the 2013 ASCO/CAP updated guideline has significant impact on HER2 classification for breast cancers with an equivocal HER2 IHC result and therefore increased the use of HER2-targeted therapy. Our data have also shown that reflex FISH is effective for final classification of the IHC equivocal cases and that polysomy 17 (CEP17 copy number >=3/cell) is present in a significantly higher proportion of cases with an equivocal HER2 FISH classification. PMID- 26895326 TI - A randomized control study of treating secondary stage II breast cancer-related lymphoedema with free lymph node transfer. AB - Microsurgical techniques are increasingly used for treating severe lymphoedema cases. The purpose of this study was to evaluate the effectiveness of free vascularized lymph node transfer (LNT) in stage II breast cancer-related lymphoedema patients in comparison with non-surgical management. During the last 3 years, 83 female patients were examined at our lymphoedema clinic. Finally, 36 cases were included in this study and randomly divided in two groups: group A patients (n = 18, mean age 47 years) underwent microsurgical LNT; followed by 6 months of physiotherapy and compression, while group B patients (n = 18, mean age 49 years) were managed by physiotherapy and compression alone for 6 months. Patients of both groups removed their elastic garments after 6 months and were re examined 1 year later. All the 36 patients had detailed evaluation of the affected extremity including limb volume measurement, infection episodes and scale scoring of pain, feeling of heaviness and functional status both at baseline and 18 month. Limb volume reduction was observed in both groups; mean reduction was greater in group A (57 %) than in group B (18 %). Infection episodes in group A were significantly reduced compared to those in group B patients. All group A patients reported painless and feeling of heaviness-free extremities with overall functional improvement, while the corresponding changes in group B patients were no more than marginal. Moreover, the LNT procedure was estimated as cost effective compared to conservative treatment alone. LNT represents an effective therapeutic approach for stage II lymphoedema patients; it significantly reduces limb volume, decreases recurrent infections and improves the overall function. PMID- 26895327 TI - Early Characteristics of Children with ASD Who Demonstrate Optimal Progress Between Age Two and Four. AB - Although for many children, Autism Spectrum Disorder (ASD) is a lifelong disability, a subset of children with ASD lose their diagnosis and show typical cognitive and adaptive abilities. The ages at which this transition can occur is not known, but it sometimes occurs quite early. Participants in the current study were 207 children with an ASD at age two who were reevaluated at age four. Eighty three percent retained an ASD diagnosis at reevaluation and 9 % showed "optimal progress": clear ASD at age two but not at age four, and average cognition, language, communication and social skills at age four. Early child-level factors predicted optimal progress: diagnosis of PDD-NOS, fewer repetitive behaviors, less severe symptomatology and stronger adaptive skills. PMID- 26895328 TI - NPAS2 Compensates for Loss of CLOCK in Peripheral Circadian Oscillators. AB - Heterodimers of CLOCK and BMAL1 are the major transcriptional activators of the mammalian circadian clock. Because the paralog NPAS2 can substitute for CLOCK in the suprachiasmatic nucleus (SCN), the master circadian pacemaker, CLOCK deficient mice maintain circadian rhythms in behavior and in tissues in vivo. However, when isolated from the SCN, CLOCK-deficient peripheral tissues are reportedly arrhythmic, suggesting a fundamental difference in circadian clock function between SCN and peripheral tissues. Surprisingly, however, using luminometry and single-cell bioluminescence imaging of PER2 expression, we now find that CLOCK-deficient dispersed SCN neurons and peripheral cells exhibit similarly stable, autonomous circadian rhythms in vitro. In CLOCK-deficient fibroblasts, knockdown of Npas2 leads to arrhythmicity, suggesting that NPAS2 can compensate for loss of CLOCK in peripheral cells as well as in SCN. Our data overturn the notion of an SCN-specific role for NPAS2 in the molecular circadian clock, and instead indicate that, at the cellular level, the core loops of SCN neuron and peripheral cell circadian clocks are fundamentally similar. PMID- 26895329 TI - Analysis of Saprolegnia parasitica Transcriptome following Treatment with Copper Sulfate. AB - BACKGROUND: Massive infection caused by oomycete fungus Saprolegnia parasitica is detrimental to freshwater fish. Recently, we showed that copper sulfate demonstrated good efficacy for controlling S. parasitica infection in grass carp. In this study, we investigated the mechanism of inhibition of S. parasitica growth by copper sulfate by analyzing the transcriptome of copper sulfate-treated S. parasitica. To examine the mechanism of copper sulfate inhibiting S. parasitica, we utilized RNA-seq technology to compare differential gene expression in S. parasitica treated with or without copper sulfate. RESULTS: The total mapped rates of the reads with the reference genome were 90.50% in the control group and 73.50% in the experimental group. In the control group, annotated splice junctions, partial novel splice junctions and complete novel splice junctions were about 83%, 3% and 14%, respectively. In the treatment group, the corresponding values were about 75%, 6% and 19%. Following copper sulfate treatment, a total 310 genes were markedly upregulated and 556 genes were markedly downregulated in S. parasitica. Material metabolism related GO terms including cofactor binding (33 genes), 1,3-beta-D-glucan synthase complex (4 genes), carboxylic acid metabolic process (40 genes) were the most significantly enriched. KEGG pathway analysis also determined that the metabolism-related biological pathways were significantly enriched, including the metabolic pathways (98 genes), biosynthesis of secondary metabolites pathways (42 genes), fatty acid metabolism (13 genes), phenylalanine metabolism (7 genes), starch and sucrose metabolism pathway (12 genes). The qRT-PCR results were largely consistent with the RNA-Seq results. CONCLUSION: Our results indicate that copper sulfate inhibits S. parasitica growth by affecting multiple biological functions, including protein synthesis, energy biogenesis, and metabolism. PMID- 26895331 TI - Scrotal-Septal Fasciocutaneous Flap Used as a Multifunctional Coverage for Prior Failed Hypospadias Repair. AB - OBJECTIVES: The study aims to report the method and outcome of using scrotal septal fasciocutaneous flap as a multifunctional coverage for prior failed hypospadias repair. METHODS: From January 2014 to June 2015, 18 hypospadias patients who have undergone repeated failed surgeries were enrolled. Their penile skin, urethral plate and dartos fascia are not enough to reconstruct the urethra, but have well-developed scrota. We performed urethroplasty by buccal mucosa free grafting and tubularized anastomosis 6 months after the urethroplasty. Then, scrotal-septal fasciocutaneous flap was used to be a multifunctional coverage on the surface of anastomotic urethra, which was a waterproof layer and cutaneous coverage. RESULTS: The skin flaps survived and the incisions healed in 18 patients. No fistula and stricture occurred. The scar of donor site seemed like a new scrotal raphe. The flap can slip slightly along with the preputial movement and retain the original sense of touch. All patients were followed up at 1 and 6 months by telephone or in person and gained good recoveries. CONCLUSION: Scrotal septal fasciocutaneous flap, including sufficient fascia tissue, reliable blood supply and skin coverage, is a good choice for the coverage of anastomotic urethra as both the waterproof layer and skin coverage, especially for hypospadias patients who have undergone several failed operations. PMID- 26895330 TI - Responses of hybrid aspen over-expressing a PIP2;5 aquaporin to low root temperature. AB - Aquaporins mediate the movement of water across cell membranes. Plasma membrane intrinsic protein 2;5 from Populus trichocarpa*deltoides (PtdPIP2;5) was previously demonstrated to be a functionally important water conducting aquaporin. To study the relevance of aquaporin-mediated root water transport at low temperatures, we generated transgenic Populus tremula*alba over-expressing PtdPIP2;5 under control of the maize ubiquitin promoter, and compared the physiological responses and water transport properties of the PtdPIP2;5 over expressing lines (PtdPIP2;5ox) with wild-type plants. We hypothesized that over expression of PtdPIP2;5 would reduce temperature sensitivity of root water transport and gas exchange. Decreasing root temperatures to 10 and 5 degrees C significantly decreased hydraulic conductivities (Lp) in wild-type plants, but had no significant effect on Lp in PtdPIP2;5ox plants. Recovery of Lp in the transgenic lines returned to 20 degrees C from 5 degrees C was faster than in the wild-type plants. Low root temperature did not induce major changes in transcript levels for other PIPs. When roots were exposed to 5 degrees C in solution culture and shoots were exposed to 20 degrees C, wild-type plants had significantly lower net photosynthetic and transpiration rates compared to PtdPIP2;5ox plants. Taken together, our results demonstrate that over-expression of PtdPIP2;5 in P. tremula*alba was effective in alleviating the effects of low root temperature on Lp and gas exchange. PMID- 26895333 TI - Biogeography and Photosynthetic Biomass of Arctic Marine Pico-Eukaroytes during Summer of the Record Sea Ice Minimum 2012. AB - Information on recent photosynthetic biomass distribution and biogeography of Arctic marine pico-eukaryotes (0.2-3 MUm) is needed to better understand consequences of environmental change for Arctic marine ecosystems. We analysed pico-eukaryote biomass and community composition in Fram Strait and large parts of the Central Arctic Ocean (Nansen Basin, Amundsen Basin) using chlorophyll a (Chl a) measurements, automated ribosomal intergenic spacer analysis (ARISA) and 454-pyrosequencing. Samples were collected during summer 2012, the year with the most recent record sea ice minimum. Chl a concentrations were highest in eastern Fram Strait and pico-plankton accounted for 60-90% of Chl a biomass during the observation period. ARISA-patterns and 454-pyrosequencing revealed that pico eukaryote distribution is closely related to water mass distribution in the euphotic zone of the Arctic Ocean. Phaeocystaceae, Micromonas sp., Dinophyceae and Syndiniales constitute a high proportion of sequence reads, while sequence abundance of autotrophic Phaeocystaceae and mixotrophic Micromonas sp. was inversely correlated. Highest sequence abundances of Phaeocystaceae were observed in the warm Atlantic Waters in Fram Strait, while Micromonas sp. dominated the abundant biosphere in the arctic halocline. Our results are of particular interest considering existing hypotheses that environmental conditions in Nansen Basin might become more similar to the current conditions in Fram Strait. We propose that in response, biodiversity and biomass of pico-eukaryotes in Nansen Basin could resemble those currently observed in Fram Strait in the future. This would significantly alter biogeochemical cycles in a large part of the Central Arctic Ocean. PMID- 26895332 TI - Cervical Lymph Node Metastasis in High-Grade Transformation of Head and Neck Adenoid Cystic Carcinoma: A Collective International Review. AB - Adenoid cystic carcinoma (AdCC) is among the most common malignant tumors of the salivary glands. It is characterized by a prolonged clinical course, with frequent local recurrences, late onset of metastases and fatal outcome. High grade transformation (HGT) is an uncommon phenomenon among salivary carcinomas and is associated with increased tumor aggressiveness. In AdCC with high-grade transformation (AdCC-HGT), the clinical course deviates from the natural history of AdCC. It tends to be accelerated, with a high propensity for lymph node metastasis. In order to shed light on this rare event and, in particular, on treatment implications, we undertook this review: searching for all published cases of AdCC-HGT. We conclude that it is mandatory to perform elective neck dissection in patients with AdCC-HGT, due to the high risk of lymph node metastases associated with transformation. PMID- 26895334 TI - ZmCCD7/ZpCCD7 encodes a carotenoid cleavage dioxygenase mediating shoot branching. AB - MAIN CONCLUSION: ZmCCD7/ZpCCD7 encodes a carotenoid cleavage dioxygenase that may mediate strigolactone biosynthesis highly responsive to phosphorus deficiency and undergoes negative selection over domestication from Zea ssp. parviglumis to Zea mays. Carotenoid cleavage dioxygenase 7 (CCD7) functions to suppress shoot branching by controlling strigolactone biosynthesis. However, little is known about CCD7 and its functions in maize and its ancestor (Zea ssp. parviglumis) with numerous shoot branches. We found that ZmCCD7 and ZpCCD7 had the same coding sequence, indicating negative selection of the CCD7 gene over domestication from Zea ssp. parviglumis to Zea mays. CCD7 expression was highly responsive to phosphorus deficiency in both species, especially in the meristematic zone and the pericycle of the elongation zone of maize roots. Notably, the crown root had the strongest ZmCCD7 expression in the meristematic zone under phosphorus limitation. Transient expression of GFP tagged ZmCCD7/ZpCCD7 in maize protoplasts indicated their localization in the plastid. Further, ZmCCD7/ZpCCD7 efficiently catalyzed metabolism of six different linear and cyclic carotenoids in E. coli, and generated beta-ionone by cleaving beta-carotene at the 9,10 (9',10') position. Together with suppression of shoot branching in the max3 mutant by transformation of ZmCCD7/ZpCCD7, our work suggested that ZmCCD7/ZpCCD7 encodes a carotenoid cleavage dioxygenase mediating strigolactone biosynthesis in maize and its ancestor. PMID- 26895335 TI - Transgenic apple plants overexpressing the chalcone 3-hydroxylase gene of Cosmos sulphureus show increased levels of 3-hydroxyphloridzin and reduced susceptibility to apple scab and fire blight. AB - MAIN CONCLUSION: Overexpression of chalcone-3-hydroxylase provokes increased accumulation of 3-hydroxyphloridzin in Malus . Decreased flavonoid concentrations but unchanged flavonoid class composition were observed. The increased 3 hydroxyphlorizin contents correlate well with reduced susceptibility to fire blight and scab. The involvement of dihydrochalcones in the apple defence mechanism against pathogens is discussed but unknown biosynthetic steps in their formation hamper studies on their physiological relevance. The formation of 3 hydroxyphloretin is one of the gaps in the pathway. Polyphenol oxidases and cytochrome P450 dependent enzymes could be involved. Hydroxylation of phloretin in position 3 has high similarity to the B-ring hydroxylation of flavonoids catalysed by the well-known flavonoid 3'-hydroxylase (F3'H). Using recombinant F3'H and chalcone 3-hydroxylase (CH3H) from Cosmos sulphureus we show that F3'H and CH3H accept phloretin to some extent but higher conversion rates are obtained with CH3H. To test whether CH3H catalyzes the hydroxylation of dihydrochalcones in planta and if this could be of physiological relevance, we created transgenic apple trees harbouring CH3H from C. sulphureus. The three transgenic lines obtained showed lower polyphenol concentrations but no shift between the main polyphenol classes dihydrochalcones, flavonols, hydroxycinnamic acids and flavan 3-ols. Increase of 3-hydroxyphloridzin within the dihydrochalcones and of epicatechin/catechin within soluble flavan 3-ols were observed. Decreased activity of dihydroflavonol 4-reductase and chalcone synthase/chalcone isomerase could partially explain the lower polyphenol concentrations. In comparison to the parent line, the transgenic CH3H-lines showed a lower disease susceptibility to fire blight and apple scab that correlated with the increased 3-hydroxyphlorizin contents. PMID- 26895336 TI - Agatharesinol biosynthesis-related changes of ray parenchyma in sapwood sticks of Cryptomeria japonica during cell death. AB - MAIN CONCLUSION: The work demonstrates a relationship between the biosynthesis of the secondary metabolite, agatharesinol, and cytological changes that occur in ray parenchyma during cell death in sapwood sticks of Cryptomeria japonica under humidity-regulated conditions. To characterize the death of ray parenchyma cells that accompanies the biosynthesis of secondary metabolites, we examined cell death in sapwood sticks of Cryptomeria japonica under humidity-regulated conditions. We monitored features of ray parenchyma cells, such as viability, the morphology of nuclei and vacuoles, and the amount of starch grains. In addition, we analyzed levels of agatharesinol, a heartwood norlignan, by gas chromatography mass spectrometry in the same sapwood sticks. Dramatic changes in the amount of starch grains and in the level of agatharesinol occurred simultaneously. Therefore, the biosynthesis of agatharesinol appeared to originate from the breakdown of starch. Furthermore, we observed the expansion of vacuoles in ray parenchyma cells prior to other cytological changes at the final stage of cell death. In our experimental system, we were able to follow the process of cell death and to demonstrate relationships between cytological changes and the biosynthesis of a secondary metabolite during the death of ray parenchyma cells. PMID- 26895337 TI - The Whats, the Wheres and the Hows of strigolactone action in the roots. AB - MAIN CONCLUSION: Strigolactones control various aspects of plant development, including root architecture. Here, we review how strigolactones act in the root and survey the strigolactone specificity of signaling components that affect root development. Strigolactones are a group of secondary metabolites produced in plants that have been assigned multiple roles, of which the most recent is hormonal activity. Over the last decade, these compounds have been shown to regulate various aspects of plant development, such as shoot branching and leaf senescence, but a growing body of literature suggests that these hormones play an equally important role in the root. In this review, we present all known root phenotypes linked to strigolactones. We examine the expression and presence of the main players in biosynthesis and signaling of these hormones and bring together the available information that allows us to explain how strigolactones act to modulate the root system architecture. PMID- 26895340 TI - Erratum to: Renal and Bone Adverse Effects of a Tenofovir-Based Regimen in the Treatment of HIV-Infected Children: A Systematic Review. PMID- 26895339 TI - Winners of the 2014 and 2015 American College of Rheumatology Annual Image Competition. PMID- 26895338 TI - Transcriptional profiling of epigenetic regulators in somatic embryos during temperature induced formation of an epigenetic memory in Norway spruce. AB - MAIN CONCLUSION: A significant number of epigenetic regulators were differentially expressed during embryogenesis at different epitype-inducing conditions. Our results support that methylation of DNA and histones, as well as sRNAs, are pivotal for the establishment of the epigenetic memory. As a forest tree species with long generation times, Norway spruce is remarkably well adapted to local environmental conditions despite having recently, from an evolutionary perspective, recolonized large areas following the last glaciation. In this species, there is an enigmatic epigenetic memory of the temperature conditions during embryogenesis that allows rapid adaptation to changing environment. We used a transcriptomic approach to investigate the molecular mechanisms underlying the formation of the epigenetic memory during somatic embryogenesis in Norway spruce. Nine mRNA libraries were prepared from three epitypes of the same genotype resulting from exposure to epitype-inducing temperatures of 18, 23 and 28 degrees C. RNA-Seq analysis revealed more than 10,000 differentially expressed genes (DEGs). The epitype-inducing conditions during SE were accompanied by marked transcriptomic changes for multiple gene models related to the epigenetic machinery. Out of 735 putative orthologs of epigenetic regulators, 329 were affected by the epitype-inducing temperatures and differentially expressed. The majority of DEGs among the epigenetic regulators was related to DNA and histone methylation, along with sRNA pathways and a range of putative thermosensing and signaling genes. These genes could be the main epigenetic regulators involved in formation of the epigenetic memory. We suggest considerable expansion of gene families of epigenetic regulators in Norway spruce compared to orthologous gene families in Populus and Arabidopsis. Obtained results provide a solid basis for further genome annotation and studies focusing on the importance of these candidate genes for the epigenetic memory formation. PMID- 26895341 TI - Comment on 'The Contribution of National Spontaneous Reporting Systems to Detect Signals of Torsadogenicity: Issues Emerging from the ARITMO Project'. PMID- 26895342 TI - Authors' Reply to Alain Braillon's Comment on "The Contribution of National Spontaneous Reporting Systems to Detect Signals of Torsadogenicity: Issues Emerging from the ARITMO Project". PMID- 26895343 TI - Measuring Signal Detection Performance: Can We Trust Negative Controls and Do We Need Them? PMID- 26895345 TI - Acceptability of intrauterine contraception among women living with human immunodeficiency virus: a randomised clinical trial. AB - OBJECTIVES: The aim of our study was to compare acceptability of the copper intrauterine device (Cu-IUD) and levonorgestrel-releasing intrauterine system (LNG-IUS) among women living with the human immunodeficiency virus (HIV). METHODS: We randomly assigned 703 HIV-positive women in Uganda to receive either a Cu-IUD or an LNG-IUS and followed them for at least one year. During the follow up visits, face-to-face interviews were conducted with the women and acceptability of the Cu-IUD or LNG-IUS was assessed, using a Likert scale, at one, three, six and twelve months. At the final follow-up visit, women were also assessed for satisfaction with either method. RESULTS: Between 9 September 2013 and 31 December 2014, 703 women were recruited and assigned as follows: 349 to a Cu-IUD group and 354 to an LNG-IUS group. Acceptability decreased from 94.3% at one month to 87.7% at 12 months in the Cu-IUD group and from 96.3% at one month to 86.7% at 12 months in the LNG-IUS group (p = 0.97). Satisfaction with intrauterine contraception was reported by 83.7% (283/338) in the Cu-IUD group and by 90.4% (302/334) in the LNG-IUS group (p = 0.50). CONCLUSIONS: There was no significant difference in acceptability between the LNG-IUS and Cu-IUD among HIV positive women. Satisfaction rates were high and similar in the two groups. Both the Cu-IUD and LNG-IUS are acceptable forms of contraception for HIV-positive women and should be made available to women in HIV care to increase their contraceptive method options. CLINICAL TRIAL REGISTRATION: The trial is registered at the Pan African Clinical Trials Registry (PACTR 201308000561212). PMID- 26895346 TI - Isotopic signature of selected lanthanides for nuclear activities profiling using cloud point extraction and ICP-MS/MS. AB - The presence of fission products, which include numerous isotopes of lanthanides, can impact the isotopic ratios of these elements in the environment. A cloud point extraction (CPE) method was used as a preconcentration/separation strategy prior to measurement of isotopic ratios of three lanthanides (Nd, Sm, and Eu) by inductively coupled plasma tandem mass spectrometry (ICP-MS/MS). To minimise polyatomic interference, the combination of interferents removal by CPE, reaction/collision cell conditions in He and NH3 mode and tandem quadrupole configuration was investigated and provided optimal results for the determination of isotopic ratio in environmental samples. Isotopic ratios were initially measured in San Joaquin soil (NIST-2709a), an area with little contamination of nuclear origin. Finally, samples collected from three sites with known nuclear activities (Fangataufa Lagoon in French Polynesia, Chernobyl and the Ottawa River near Chalk River Laboratory) were analysed and all exhibited altered isotopic ratios for (143/145)Nd, (147/149)Sm, and (151/153)Eu. These results demonstrate the potential of CPE and ICP-MS/MS for the detection of altered isotopic ratio in environmental samples collected in area subjected to nuclear anthropogenic contamination. The detection of variations in these isotopic ratios of fission products represents the first application of CPE in nuclear forensic investigations of environmental samples. PMID- 26895347 TI - Measurement and estimation of radiocesium discharge rate from paddy field during land preparation and mid-summer drainage. AB - In this research, we evaluated the range of (137)Cs discharge rates from paddy fields during land preparation and mid-summer drainage. First, we investigated (137)Cs discharge loads during land preparation and mid-summer drainage and their ratio to the (137)Cs inventory of paddy field soil. We found that total discharge rates were 0.003-0.028% during land preparation and 0.001-0.011% during mid summer drainage. Next, we validated the range of obtained total discharge of (137)Cs from the paddy fields using a simplified equation and literature review. As a result, we conclude that the range of total outflow loads of suspended solids for the investigated paddy field was generally representative of paddy fields in Japan. Moreover, the (137)Cs discharge ratio had a wide range, but was extremely small relative to (137)Cs present in paddy field soil before irrigation. PMID- 26895348 TI - Controlled initial surge despite high drug fraction and high solubility. AB - Potential connections between release profiles and solvent evaporation rates alongside polymer chemistry were elucidated for the release of tetracycline hydrochloride from two different poly (d, l-lactide-co-glycolide) (PLGA) film matrices containing high drug fractions (50%, 30%, and 15%), and prepared at two distinct solvent evaporation rates. At highest tetracycline concentrations (50%), (i) the early release rates were <=0.5 MUg/min in all cases; (ii) release was linear from systems fabricated with lower lactic content and slower solvent evaporation rate and bimodal from systems fabricated with higher lactic content and faster evaporation rate; (iii) surface fractions covered by the drug were similar at both evaporation rates for 85:15 PLGA but very different for 50:50 PLGA, leading to unexpectedly reduced early release from 50:50 PLGA than from 85:15 PLGA when both the matrices were fabricated using a slower evaporation rate. These features remained unaffected in case of low drug concentration. Results suggested that during the formation of the drug-polymer microstructure, the combined effect of polymer chemistry and solvent evaporation rate sets apart the surface characteristics and the initial release profiles of systems containing high drug fraction, and an appropriate combination of these parameters may be utilized to control the early stage of drug release. PMID- 26895350 TI - Mini Review of the Cost-Effectiveness of Unilateral Osseointegrated Implants in Adults: Possibly Cost-Effective for the Correct Indication. AB - An osseointegrated implant (e.g. bone-anchored hearing aid, BAHA) is a surgically implantable device for unilateral sensorineural and unilateral or bilateral conductive hearing loss in patients who otherwise cannot use or do not prefer a conventional air conduction hearing aid (ACHA). The specific indications for an osseointegrated implant are evolving and dependent upon the country or regulatory body overseeing the provision of these devices. However, there are general groups of patients who would be likely to benefit, one such group being patients with congenital aural atresia. Given the anatomical aberrancies with aural atresia, these subjects cannot wear ACHAs. Another group of patients who may benefit from an osseointegrated implant over an ACHA are patients with chronically draining otological infections. As the provision of an osseointegrated implant requires a surgical procedure, there are inherent direct and indirect costs associated with its use beyond those required for an ACHA. Consideration of outcomes and cost effectiveness for the osseointegrated implant versus the ACHA is prudent prior to making policy decisions in a setting of limited health care resources. We performed a mini review on all available cost-effectiveness analyses of osseointegrated implants published in Medline. There are only 2 contemporary cost effectiveness analyses published to date. There is limited quality of life data available for patients living with an osseointegrated implant. As a result, the cost-effectiveness of the osseointegrated implant, specifically the BAHA, compared to conventional hearing aid devices remains unclear. However, there are clear indications for the BAHA when a standard hearing aid cannot be used (e.g. chronic draining ear) or in single-sided severe-to-profound hearing loss with reasonable hearing in the contralateral ear. The BAHA should not be considered interchangeable with the ACHA with regard to cost-effectiveness, but rather considered as an effective option for the patient for the correct indication. PMID- 26895349 TI - Low Concordance between Gene Expression Signatures in ER Positive HER2 Negative Breast Carcinoma Could Impair Their Clinical Application. AB - BACKGROUND: Numerous prognostic gene expression signatures have been recently described. Among the signatures there is variation in the constituent genes that are utilized. We aim to evaluate prognostic concordance among eight gene expression signatures, on a large dataset of ER positive HER2 negative breast cancers. METHODS: We analysed the performance of eight gene expression signatures on six different datasets of ER+ HER2- breast cancers. Survival analyses were performed using the Kaplan-Meier estimate of survival function. We assessed discrimination and concordance between the 8 signatures on survival and recurrence rates The Nottingham Prognostic Index (NPI) was used to to stratify the risk of recurrence/death. RESULTS: The discrimination ability of the whole signatures, showed fair discrimination performances, with AUC ranging from 0.64 (95%CI 0.55-0.73 for the 76-genes signatures, to 0.72 (95%CI 0.64-0.8) for the Molecular Prognosis Index T17. Low concordance was found in predicting events in the intermediate and high-risk group, as defined by the NPI. Low risk group was the only subgroup with a good signatures concordance. CONCLUSION: Genomic signatures may be a good option to predict prognosis as most of them perform well at the population level. They exhibit, however, a high degree of discordance in the intermediate and high-risk groups. The major benefit that we could expect from gene expression signatures is the standardization of proliferation assessment. PMID- 26895351 TI - Exopolysaccharide fraction from Pediococcus pentosaceus KFT18 induces immunostimulatory activity in macrophages and immunosuppressed mice. AB - AIMS: Exopolysaccharide fraction from Pediococcus pentosaceus KFT18 (PE-EPS), a lactic acid bacteria isolated from Kimchi (a Korean fermented vegetable product), was preliminary characterized and its immunostimulating effects were analysed. METHODS AND RESULTS: In this study, we used interferon-gamma (IFN-gamma)-primed RAW 264.7 macrophages and CD3/CD28-stimulated splenocytes to determine the immunotimulatory activities of PE-EPS. Upon exposure to PE-EPS, IFN-gamma-primed RAW 264.7 macrophages showed significant increases in the expressions of inducible nitric oxide synthase (iNOS), tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-6 and IL-1beta. Molecular data using reporter gene assay and electrophoretic mobility shift assay (EMSA) revealed that PE-EPS upregulated transcriptional activity, DNA binding and the nuclear translocation of nuclear factor-kappaB (NF-kappaB). Furthermore, PE-EPS enhanced anti-CD3/CD28-specific proliferation and the productions of IL-2 and IFN-gamma in primary splenocytes. In cyclophosphamide-induced immunosuppressed mice, pretreatment with PE-EPS (5, 15 or 45 mg kg(-1) day(-1), p.o.) increased thymus and spleen indices, and improved lymphocyte and neutrophil counts. CONCLUSION: PE-EPS stimulated the IFN gamma-primed macrophages and primary splenocytes to induce immune responses and improved the cyclophosphamide-induced immunosuppression in mice. SIGNIFICANCE AND IMPACT OF THE STUDY: The results in this study improved our understanding of immunostimulating activity of PE-EPS and supported its potential treatment option as a natural immunostimulant. PMID- 26895352 TI - Neurodevelopmental correlates of proneness to guilt and shame in adolescence and early adulthood. AB - Investigating how brain development during adolescence and early adulthood underlies guilt- and shame-proneness may be important for understanding risk processes for mental disorders. The aim of this study was to investigate the neurodevelopmental correlates of interpersonal guilt- and shame-proneness in healthy adolescents and young adults using structural magnetic resonance imaging (sMRI). Sixty participants (age range: 15-25) completed sMRI and self-report measures of interpersonal guilt- and shame-proneness. Independent of interpersonal guilt, higher levels of shame-proneness were associated with thinner posterior cingulate cortex (PCC) thickness and smaller amygdala volume. Higher levels of shame-proneness were also associated with attenuated age-related reductions in thickness of lateral orbitofrontal cortex (lOFC). Our findings highlight the complexities in understanding brain-behavior relationships during the adolescent/young adult period. Results were consistent with growing evidence that accelerated cortical thinning during adolescence may be associated with superior socioemotional functioning. Further research is required to understand the implications of these findings for mental disorders characterized by higher levels of guilt and shame. PMID- 26895353 TI - In Situ Generation of ArCu from CuF2 Makes Coupling of Bulky Aryl Silanes Feasible and Highly Efficient. AB - A bimetallic system of Pd/CuF2, catalytic in Pd and stoichiometric in Cu, is very efficient and selective for the coupling of fairly hindered aryl silanes with aryl, anisyl, phenylaldehyde, p-cyanophenyl, p-nitrophenyl, or pyridyl iodides of conventional size. The reaction involves the activation of the silane by Cu(II), followed by disproportionation and transmetalation from the Cu(I)(aryl) to Pd(II), upon which coupling takes place. Cu(III) formed during disproportionation is reduced to Cu(I)(aryl) by excess aryl silane, so that the CuF2 system is fully converted into Cu(I)(aryl) and used in the coupling. Moreover, no extra source of fluoride is needed. Interesting size selectivity towards coupling is found in competitive reactions of hindered aryl silanes. Easily accessible [PdCl2 (IDM)(AsPh3)] (IDM = 1,3-dimethylimidazol-2-ylidene) is by far the best catalyst, and the isolated products are essentially free from As or Pd (<1 ppm). The mechanistic aspects of the process have been experimentally examined and discussed. PMID- 26895354 TI - Evaluating Iatrogenic Complications of the Total-Contact Cast: An 8-Year Retrospective Review at Cleveland Clinic. AB - BACKGROUND: Total-contact casting is an effective method to treat various pathologic abnormalities in patients with diabetic neuropathy, but its use is frequently associated with iatrogenic complications. METHODS: The largest retrospective review to date of iatrogenic complications of total-contact casts was conducted over an 8-year period at Cleveland Clinic. RESULTS: In the past 8 years, 23% of patients developed complications, and the most common complication was a new heel ulcer formation. Of these complications, 92.1% resolved, 6.4% were lost to follow-up, and 1.4% resulted in a partial foot amputation. Mean cast duration was 10.3 days for patients who developed a total-contact cast iatrogenic complication. The most common indication for the use of a total-contact cast was a neuropathic foot ulceration. CONCLUSIONS: The results of this study support the use of total-contact casting in the insensate patient with diabetes. However, adequate staff training in total-contact cast application is recommended to reduce complications. PMID- 26895356 TI - Influence of Children's Foot Type on Their Physical Motor Performance. AB - BACKGROUND: This cross-sectional study aimed to determine whether normal, flat, or high-arched feet corresponded to better performance of certain motor tests in children. METHODS: One hundred eighty-seven children (mean +/- SD age, 11.15 +/- 1.24 years) were recruited and divided into three groups: 96 with normal feet, 54 with high-arched feet, and 37 with low-arched feet. Nine motor trials were selected to assess motor performance: standing long jump, standing triple jump from each foot, standing vertical jump, shuttle run 10 * 5 m, standing-start 20-m sprint, static balance, dynamic balance on a beam of an inverted gym bench, and agility circuit. RESULTS: There were no significant differences in the trial results between groups, although in eight of the nine trials participants in the high-arched group tended to perform better. Boys performed better than girls in all of the trials except those of balance. CONCLUSIONS: These results suggest that children with a certain foot type did not achieve better motor performance in the nine trials tested. PMID- 26895357 TI - Cheilectomy as a First-Line Surgical Treatment Option Yields Good Functional Results in Grade III Hallux Rigidus. AB - BACKGROUND: This study aimed to analyze the functional results of cheilectomy in the surgical treatment of grade III hallux rigidus and to evaluate whether cheilectomy is a preferable first-line treatment over other surgical methods. METHODS: Of 29 patients with moderate daily physical activity who underwent cheilectomy between 2009 and 2012 on being diagnosed as having grade III hallux rigidus according to the Coughlin-Shurnas grading system, 21 patients (14 women and 7 men; mean age, 59.2 years; age range, 52-67 years) (22 feet) with regular follow-up and complete medical records were included in the study. The patients were evaluated in the preoperative and postoperative periods using a visual analog scale for pain and the American Orthopaedic Foot and Ankle Society metatarsophalangeal assessment forms. RESULTS: The preoperative mean American Orthopaedic Foot and Ankle Society score of 53 (range, 29-67) improved to 78 (range, 57-92) postoperatively (Wilcoxon test P = .001). The preoperative mean visual analog scale score of 89 (range, 60-100) improved to 29 (range, 0-70) in the postoperative period (Wilcoxon test P = .001). CONCLUSIONS: As a simple and repeatable procedure that allows for further joint-sacrificing surgical procedures when required, cheilectomy is a preferable method to be applied as a first-line option for the surgical treatment of grade III hallux rigidus. PMID- 26895355 TI - Foot Complications and Mortality: Results from Translating Research Into Action for Diabetes (TRIAD). AB - BACKGROUND: We sought to study the impact of foot complications on 10-year mortality independent of other demographic and biological risk factors in a racially and socioeconomically diverse managed-care population with access to high-quality medical care. METHODS: We studied 6,992 patients with diabetes in Translating Research Into Action for Diabetes (TRIAD), a prospective observational study of diabetes care in managed care. Foot complications were assessed using administrative claims data. The National Death Index was searched for deaths across 10 years of follow-up (2000-2009). RESULTS: Charcot's neuro osteoarthropathy and diabetic foot ulcer with debridement were associated with an increased risk of mortality; however, the associations were not significant in fully adjusted models. Lower-extremity amputation (LEA) was associated with an increased risk of mortality in unadjusted (hazard ratio [HR], 3.21; 95% confidence interval [CI], 2.50-4.12) and fully adjusted (HR, 1.84; 95% CI, 1.28 2.63) models. When we examined the associations between LEA and mortality stratified by sex and race, risk was increased in men (HR, 1.96; 95% CI, 1.25 3.07), Hispanic individuals (HR, 5.17; 95% CI, 1.48-18.01), and white individuals (HR, 2.18; 95% CI, 1.37-3.47). In sensitivity analyses, minor LEA tended to increase the risk of mortality (HR, 1.48; 95% CI, 0.92-2.40), and major LEA was associated with a significantly higher risk of death at 10 years (HR, 1.89; 95% CI, 1.18-3.01). CONCLUSIONS: In this managed-care population with access to high quality medical care, LEA remained a robust independent predictor of mortality. The association was strongest in men and differed by race. PMID- 26895358 TI - Assessment and Diagnosis of Posterior Tibial Tendon Dysfunction: Do We Share the Same Opinions and Beliefs? AB - BACKGROUND: Posterior tibial tendon dysfunction is a disabling pathologic flatfoot disorder. Evidence supports the notion that this condition is poorly diagnosed by health-care professionals. In addition, opinion is divided as to the most appropriate assessment and diagnostic techniques used to reflect the progression or stage of the condition. Hence, this study intended to explore the views and opinions of health-care professionals who may be involved in its assessment and diagnosis. METHODS: A two-phase sequential mixed methods design was used that combined a questionnaire survey and a focus group interview. RESULTS: The questionnaire data were analyzed using the Kendall levels of concordance and the Cohen kappa statistic, and the focus group data were analyzed using thematic analysis, which led to three main themes: resource implications, scope of practice, and awareness of the condition. CONCLUSIONS: This study highlights what may have been suspected previously but that has never been investigated in a structured manner. One approach to the assessment and diagnosis of posterior tibial tendon dysfunction is not necessarily the best, and depending on the clinical teams, different guidance may be required to ensure that patients are receiving the most appropriate and best care. PMID- 26895360 TI - Erratum. PMID- 26895359 TI - Dynamic Flexion Stiffness of Foot Joints During Walking. AB - BACKGROUND: Dynamic stiffness can be used for studying foot pathologic abnormalities and for developing prostheses and orthoses. Although previous works have studied the role of ankle joint stiffness during gait, other foot joints have not yet been analyzed. We sought to characterize the dynamic stiffness of the ankle, midtarsal, and metatarsophalangeal joints during normal walking. METHODS: Kinematics and contact data from four healthy individuals during walking were registered with a three-dimensional motion analysis system and a pressure platform. Stance phases with flexion moment-angle linear relationships were identified, and dynamic stiffnesses were calculated from the slope of their linear regressions. Intraparticipant repeatability was analyzed using analyses of variance, and interparticipant variability was checked through the SD of averaged participant stiffnesses. RESULTS: Flexion moment-angle linear relationships were identified (R(2) > 0.98) during the early and late midstance phases and the propulsion phase at the ankle (2.76, 5.23, and 3.42 N.m/kg/rad, respectively) and midtarsal (15.88, 3.90, and 4.64 N.m/kg/rad, respectively) joints. At the metatarsophalangeal joint, a linear relationship (R(2) > 0.96) occurred only during the propulsion phase (0.11 N.m/kg/rad). High dynamic stiffness variability was observed during the late and early midstance phases at the ankle and midtarsal joints, respectively. CONCLUSIONS: These results may serve as a basis for future studies aimed at investigating the role of dynamic stiffness identified herein in different foot disorders. The importance of properly controlling the samples in such studies is highlighted. Study of the dynamic stiffnesses identified might be used in the design of prostheses, orthoses, and other assistive devices. PMID- 26895361 TI - A Long-Term Study of the Effect of Subtalar Arthrodesis on the Ankle and Hindfoot Joints. AB - BACKGROUND: Subtalar arthrodesis is a common therapy for subtalar joint disorders. In this article, we evaluate the effect of subtalar arthrodesis on the ankle and hindfoot joints. METHODS: Fifty patients (33 men and 17 women) underwent subtalar arthrodesis between January 1, 1996, and August 31, 2011. The 36-item Short-Form Health Survey and American Orthopaedic Foot and Ankle Society ankle hindfoot scores were used for clinical evaluation. Radiographic analysis included assessment of degenerative changes and ankle and hindfoot joint function in the frontal and sagittal planes. RESULTS: Thirty-seven patients (27 men and 10 women; mean age, 42.6 years) were followed up for an average of 9.2 years (range, 2-17 years). The mean +/- SD 36-item Short-Form Health Survey score improved from 30.21 +/- 7.19 before surgery to 78.50 +/- 12.23, and the American Orthopaedic Foot and Ankle Society ankle hindfoot score increased from 50.32 +/- 12.39 to 73.14 +/- 15.44. Degenerative changes in the talonavicular, calcaneocuboid, metatarsocuboid, and ankle joints occurred. The talar-vertical angle was positively related to the tibial-plantar minimal angle (affected side: r = 0.56; P < .01; healthy side: r = 0.46; P < .01). The difference in hindfoot height is positively related to the difference in tibial-plantar minimal angle (r = 0.54; P < .01). CONCLUSIONS: Subtalar arthrodesis is effective treatment for subtalar joint disease but could induce joint degeneration and ankle joint motion limitation related to talar declination and hindfoot height. PMID- 26895362 TI - Pathologic Disorders of the Foot in Professional Female Flamenco Dancers. AB - BACKGROUND: The foot is the main element of artistic creation in flamenco dancing. At the professional level, the foot undergoes high musculoskeletal demands, predisposing the development of podiatric pathologic disorders in this group. The principal objective of this study was to determine the most common foot lesions in professional female flamenco dancers. METHODS: In a cross sectional observational study of 44 female professional flamenco dancers, the participants completed a short questionnaire about their demographic features, number of hours danced per week, and years of professional activity. Any foot lesions presented by the participant were also recorded. RESULTS: Some type of pathologic foot condition was noted in 75% of the women, with a particularly high prevalence of hallux abducto valgus (61.4%), hypermobility of the first ray (43.2%), claw toe (40.9%), and varus fifth toe (37.5%) compared with the general population. No significant differences in the presence of pathologic disorders of the foot were found according to the time dedicated to dance or the years of professional activity. CONCLUSIONS: Female flamenco dancers in this study had a high prevalence of podiatric medical problems: some kind of pathologic abnormality of the foot was present in 75% of the participants. Hallux abducto valgus, claw toe, and hypermobility of the first ray were the most common pathologic disorders observed. PMID- 26895363 TI - The Use of Rubrics in the Clinical Evaluation of Podiatric Medical Students: Objectification of the Subjective Experience. AB - BACKGROUND: We assessed the differences in podiatric medical students' clinical professionalism objective scores (CPOSs) by comparing a previous nonrubric evaluation tool with a more recently implemented objective-centered rubric evaluation tool. This type of study has never been performed or reported on in the podiatric medical education literature. METHODS: We conducted a retrospective analysis of 89 third-year podiatric medical students between academic years 2010 2011 and 2011-2012. A Pearson correlation coefficient analysis was performed to compare CPOSs from the students' first (CPOS1) and second (CPOS2) rotations. A correlation analysis was performed comparing students' grade point averages (GPAs) with each of the individual CPOSs to verify the validity of the rubric evaluation tool. RESULTS: The Pearson correlation coefficients for the relationship between 2012 CPOS1 and CPOS2 and GPA were r = 0.233 (P <= .093) and r = 0.290 (P < .035) and for the relationship between 2013 CPOS1 and CPOS2 and GPA were r = 0.525 (P = .001) and r = 0.730 (P < .001). CONCLUSIONS: These findings suggest that the use of a rubric in the evaluation of podiatric medical students' CPOSs is correlated with their GPAs, and CPOS2 demonstrated a higher correlation than CPOS1. We believe that implementation of the rubric evaluation tool has increased the accuracy of the evaluation of podiatric medical students with respect to CPOSs. PMID- 26895364 TI - Assessment of a Cultural Competency Program in Podiatric Medical Education. AB - BACKGROUND: Des Moines University College of Podiatric Medicine and Surgery (CPMS) is implementing a cultural competency program for third-year podiatric medical students. This study assessed the effectiveness of the new educational program on cultural competency at CPMS by comparing pretest and posttest scores of students from the CPMS graduating classes of 2013 and 2014. METHODS: Students from the class of 2013 completed a 10-week online course on cultural competency, and the class of 2014 students did not. A pretest and posttest survey was used to assess cultural competency. The questions were categorized to assess either knowledge acquisition or attitudinal change. The 2013 students completed the pretest before the course and a posttest after completing the course. Without taking the course, 2014 students completed the same pretest and posttest separated by 10 weeks. A repeated-measures analysis of variance was used to compare the knowledge acquisition scores and attitudinal change scores. RESULTS: The repeated-measures analysis of variance revealed a significant interaction effect of taking the attitudinal change course (F(1,77) = 15.2; P < .001). The course did not show a significant interaction on knowledge acquisition (F(1,77) = 0.72; P > .05). CONCLUSIONS: The analysis showed a statistically significant improvement in attitudinal change scores. The study suggests that there needs to be a greater knowledge acquisition component to the cultural competency course at CPMS. PMID- 26895365 TI - Eccrine Syringofibroadenoma of the Heel: A Case Report. AB - Eccrine syringofibroadenoma is a rare, benign tumor of eccrine ductal differentiation, typically presenting in the extremities. Herein we report a case of a 77-year-old man with pain in the lateral midfoot and the presence of an eccrine syringofibroadenoma lesion in the lateral heel. On surgical excision of the lesion, the foot pain promptly resolved, and at the most recent follow-up visit, the patient remained pain free. PMID- 26895366 TI - Azole Resistance in Dermatophytes: Prevalence and Mechanism of Action. AB - Azole antifungal agents (eg, fluconazole and itraconazole) have been widely used to treat superficial fungal infections caused by dermatophytes and, unlike the allylamines (such as terbinafine and naftifine), have been associated with resistance development. Although many published manuscripts describe resistance to azoles among yeast and molds, reports describing resistance of dermatophytes are starting to appear. In this review, I discuss the mode of action of azole antifungals and mechanisms underlying their resistance compared with the allylamine class of compounds. Data from published and original studies were compared and summarized, and their clinical implications are discussed. In contrast to the cidal allylamines, static drugs such as azoles permit the occurrence of mutations in enzymes involved in ergosterol biosynthesis, and the ergosterol precursors accumulating as a consequence of azole action are not toxic. Azole antifungals, unlike allylamines, potentiate resistance development in dermatophytes. PMID- 26895372 TI - The use of ultrasound guidance for perioperative neuraxial and peripheral nerve blocks in children. AB - BACKGROUND: The use of ultrasound guidance for regional anaesthesia has become popular over the past two decades. However, it is not recognized by all experts as an essential tool. The cost of an ultrasound machine is substantially higher than the cost of other tools such as a nerve stimulator. OBJECTIVES: To determine whether ultrasound guidance offers any clinical advantage when neuraxial and peripheral nerve blocks are performed in children in terms of increasing the success rate or decreasing the rate of complications. SEARCH METHODS: We searched the following databases to March 2015: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (OvidSP), EMBASE (OvidSP) and Scopus (from inception to 27 January 2015). SELECTION CRITERIA: We included all parallel randomized controlled trials (RCTs) that evaluated the effects of ultrasound guidance used when a regional blockade technique was performed in children, and that included any of our selected outcomes. DATA COLLECTION AND ANALYSIS: We assessed selected studies for risk of bias by using the assessment tool of The Cochrane Collaboration. Two review authors independently extracted data. We graded the level of evidence for each outcome according to the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) Working Group scale. MAIN RESULTS: We included 20 studies (1241 participants) for which the source of funding was a government organization (two studies), a charitable organization (one study), an institutional department (four studies) or an unspecified source (11 studies); two studies declared that they received help from the industry (equipment loan). In 14 studies (939 participants), ultrasound guidance increased the success rate by decreasing the occurrence of a failed block: risk difference (RD) -0.11 (95% confidence interval (CI) -0.17 to -0.05); I(2) = 64%; number needed for additional beneficial outcome for a peripheral nerve block (NNTB) 6 (95% CI 5 to 8). Blocks were performed under general anaesthesia (usual clinical practice in this population); therefore, haemodynamic changes to the surgical stimulus (rather than classic sensory/motor blockade evaluation) were used to define success. For peripheral nerve blocks, the younger the child, the greater was the benefit. In eight studies (414 participants), pain scores at one hour in the post-anaesthesia care unit were reduced when ultrasound guidance was used; however, the clinical relevance of the difference was unclear (equivalent to -0.2 on a scale from 0 to 10). In eight studies (358 participants), block duration was longer when ultrasound guidance was used: standardized mean difference (SMD) 1.21 (95% CI 0.76 to 1.65; I(2) = 73%; equivalent to 62 minutes). Here again, younger children benefited most from ultrasound guidance. Time to perform the procedure was reduced when ultrasound guidance was used for pre-scanning before a neuraxial block (SMD -1.97, 95% CI -2.41 to -1.54; I(2) = 0%; equivalent to 2.4 minutes; two studies with 122 participants) or as an out-of-plane technique (SMD -0.68, 95% CI -0.96 to -0.40; I(2) = 0%; equivalent to 94 seconds; two studies with 204 participants). In two studies (122 participants), ultrasound guidance reduced the number of needle passes required to perform the block (SMD -0.90, 95% CI -1.27 to -0.52; I(2) = 0%; equivalent to 0.6 needle pass per participant). For two studies (204 participants), we could not demonstrate a difference in the incidence of bloody puncture when ultrasound guidance was used for neuraxial blockade, but we found that the number of participants was well below the optimal information size (RD -0.07, 95% CI -0.19 to 0.04). No major complications were reported for any of the 1241 participants. We rated the quality of evidence as high for success, pain scores at one hour, block duration, time to perform the block and number of needle passes. We rated the quality of evidence as low for bloody punctures. AUTHORS' CONCLUSIONS: Ultrasound guidance seems advantageous, particularly in young children, for whom it improves the success rate and increases the block duration. Additional data are required before conclusions can be drawn on the effect of ultrasound guidance in reducing the rate of bloody puncture. PMID- 26895373 TI - BaAl4 derivative phases in the sections {La,Ce}Ni2Si2-{La,Ce}Zn2Si2: phase relations, crystal structures and physical properties. AB - Phase relations and crystal structures have been evaluated within the sections LaNi2Si2-LaZn2Si2 and CeNi2Si2-CeZn2Si2 at 800 degrees C using electron microprobe analysis and X-ray powder and single crystal structure analyses. Although the systems La-Zn-Si and Ce-Zn-Si at 800 degrees C do not reveal compounds such as "LaZn2Si2" or "CeZn2Si2", solid solutions {La,Ce}(Ni1-xZnx)2Si2 exist with the Ni/Zn substitution starting from {La,Ce}Ni2Si2 (ThCr2Si2-type; I4/mmm) up to x = 0.18 for Ce(Ni1-xZnx)2Si2 and x = 0.125 for La(Ni1-xZnx)2Si2. For higher Zn-contents 0.25 <= x <= 0.55 the solutions adopt the CaBe2Ge2-type (P4/nmm). The investigations are backed by single crystal X-ray diffraction data for Ce(Ni0.61Zn0.39)2Si2 (P4/nmm; a = 0.41022(1) nm, c = 0.98146(4) nm; RF = 0.012) and by Rietveld refinement for La(Ni0.56Zn0.44)2Si2 (P4/nmm; a = 0.41680(6) nm, c = 0.99364(4) nm; RF = 0.043). Interestingly, the Ce-Zn-Si system contains a ternary phase CeZn2(Si1-xZnx)2 of the ThCr2Si2 structure type (0.25 <= x <= 0.30 at 600 degrees C), which forms peritectically at T = 695 degrees C but does not include the composition "CeZn2Si2". The primitive high temperature tetragonal phase with the CaBe2Ge2-type has also been observed for the first time in the Ce-Ni-Si system at CeNi2+xSi2-x, x = 0.33 (single crystal data, P4/nmm; a = 0.40150(2) nm, c = 0.95210(2) nm; RF = 0.0163). Physical properties (from 400 mK to 300 K) including specific heat, electrical resistivity and magnetic susceptibility have been elucidated for Ce(Ni0.61Zn0.39)2Si2 and La(Ni0.56Zn0.44)2Si2. Ce(Ni0.61Zn0.39)2Si2 exhibits a Kondo-type ground state. Low temperature specific heat data of La(Ni0.56Zn0.44)2Si2 suggest a spin fluctuation scenario with an enhanced value of the Sommerfeld constant. PMID- 26895375 TI - The impact of thermal treatment and cooling methods on municipal solid waste incineration bottom ash with an emphasis on Cl. AB - Municipal solid waste incineration (MSWI) bottom-ash products possess qualifications to be utilized in cement production. However, the instant use of bottom ash is inhibited by a number of factors, among which the chlorine (Cl) content is always strictly restricted. In this paper, the unquenched MSWI bottom ash was used as the experimental substance, and the influences of thermal treatment and cooling methods on the content and existence of Cl in the ash residues were investigated. The characterization of the MSWI bottom-ash samples examined by utilizing X-ray diffraction, optical microscopy, scanning electron microscopy/energy dispersive X-ray spectroscopy. The experimental results show that as a function of thermal treatment, the reduction rate of Cl is slight below 15.0%, which is relatively low compared with water washing process. Different cooling methods had impacts on the existing forms of Cl. It was understood that most of Cl existed in the glass phase if the bottom ash was air cooled. Contrarily in case of water-quenched bottom ash, Cl could also be accumulated in the newly-formed quench products as chloride salts or hydrate substances such as Friedel's salt. PMID- 26895374 TI - Warm Parenting Associated with Decreasing or Stable Child BMI during Treatment. AB - BACKGROUND: While authoritative parenting, which includes high levels of warmth and behavioral control, has been associated with lower risk of obesity, little is known about how general parenting impacts child weight loss during treatment. Our goal was to examine the relationship between several general parenting dimensions and 'decreasing /stable' child BMI during a 16-week family-based behavioral weight control program. METHODS: Forty-four overweight parent-child dyads (child age 8 to 12 years) enrolled in the program. Families were videotaped at baseline eating dinner in their home. Using the General Parenting Observational Scale (GPOS), meals were coded for several general parenting dimensions. Primary outcome was percent of children whose BMI 'decreased or stayed the same.' Multivariable logistic regression was used to determine the relationship between general parenting and decreasing/stable child BMI. RESULTS: Forty families (91%) completed the program. Children had a mean BMI change of -0.40 (SD 1.57), which corresponds to a -0.15 (SD 0.20) change in BMI z-score (BMI-Z); 75% of children had decreasing/stable BMI. In the unadjusted models, lower parent BMI, higher parent education, and higher levels of parental warmth were significantly associated with decreasing/stable child BMI. In the multivariable model, only higher level of warmth was associated with increased odds of decreasing/stable child BMI (OR = 1.28; 95% CI, 1.01, 1.62). CONCLUSIONS: Baseline parental warmth may influence a child's ability to lower/maintain BMI during a standard family based behavioral weight control program. Efforts to increase parent displays of warmth and emotional support towards their overweight child may help to increase the likelihood of treatment success. PMID- 26895376 TI - The lectin-like oxidized LDL receptor-1: a new potential molecular target in colorectal cancer. AB - The identification of new biomarkers and targets for tailored therapy in human colorectal cancer (CRC) onset and progression is an interesting challenge. CRC tissue produces an excess of ox-LDL, suggesting a close correlation between lipid dysfunction and malignant transformation. Lectin-like oxidized LDL receptor-1 (LOX-1) is involved in several mechanisms closely linked to tumorigenesis. Here we report a tumor specific LOX-1 overexpression in human colon cancers: LOX-1 results strongly increased in the 72% of carcinomas (P<0.001), and strongly overexpressed in 90% of highly aggressive and metastatic tumours (P<0.001), as compared to normal mucosa. Moreover LOX-1 results modulated since the early stage of the disease (adenomas vs normal mucosa; P<0.001) suggesting an involvement in tumor insurgence and progression. The in vitro knockdown of LOX-1 in DLD-1 and HCT-8 colon cancer cells by siRNA and anti-LOX-1 antibody triggers to an impaired proliferation rate and affects the maintenance of cell growth and tumorigenicity. The wound-healing assay reveals an evident impairment in closing the scratch. Lastly knockdown of LOX-1 delineates a specific pattern of volatile compounds characterized by the presence of a butyrate derivative, suggesting a potential role of LOX-1 in tumor-specific epigenetic regulation in neoplastic cells. The role of LOX-1 as a novel biomarker and molecular target represents a concrete opportunity to improve current therapeutic strategies for CRC. In addition, the innovative application of a technology focused to the identification of LOX-1 driven volatiles specific to colorectal cancer provides a promising diagnostic tool for CRC screening and for monitoring the response to therapy. PMID- 26895378 TI - ZEB2 inhibits HBV transcription and replication by targeting its core promoter. AB - Hepatitis B virus (HBV) infection is a major cause of liver diseases, especially liver cirrhosis and hepatocellular carcinoma. However, the interaction between host and HBV has not been fully elucidated. ZEB2 is a Smad-interacting, multi zinc finger protein that acts as a transcription factor or repressor for several signaling pathways. This study found that the expression of ZEB2 was decreased in HBV-expressing cells. Overexpression of ZEB2 inhibited HBV DNA replicative intermediates, 3.5kb mRNA, core protein level, and the secretion of HBsAg and HBeAg. In contrast, ZEB2 knockdown promoted HBV replication. Furthermore, ZEB2 could bind to HBV core promoter and inhibit its promoter activity. Mutation at the ZEB2 binding site in HBV core promoter eradicated ZEB2-mediated inhibition of HBV replication. This study identifies ZEB2 as a novel host restriction factor that inhibits HBV replication in hepatocytes. These data may shed light on development of new antiviral strategies. PMID- 26895377 TI - miR-30e controls DNA damage-induced stress responses by modulating expression of the CDK inhibitor p21WAF1/CIP1 and caspase-3. AB - MicroRNAs (miRNAs), a class of small non-coding RNAs that usually cause gene silencing by translational repression or degradation of mRNAs, are implicated in DNA damage-induced stress responses. To identify senescence-associated miRNAs, we performed microarray analyses using wild-type and p53-deficient HCT116 colon carcinoma cells that following gamma-irradiation (gammaIR) are driven into senescence and apoptosis, respectively. Several miRNAs including miR-30e were found upregulated in a p53-dependent manner specifically in senescent cells, but not in apoptotic cells. Overexpression of miR-30e in HCT116 cells not only inhibited gammaIR-, etoposide- or miR-34a-induced caspase-3-like DEVDase activities and cell death, but greatly accelerated and augmented their senescent phenotype. Consistently, procaspase-3 protein, but not mRNA decreased in the presence of miR-30e, whereas expression of the cyclin-dependent kinase inhibitor p21 increased both at the mRNA and protein level. Performing luciferase reporter gene assays, we identified the 3'-UTR of the caspase-3 mRNA as a direct miR-30e target. In contrast, although miR-30e was unable to bind to the p21 mRNA, it increased expression of a luciferase construct containing the p21 promoter, suggesting that the miR-30e-mediated upregulation of p21 occurs indirectly at the transcriptional level. Interestingly, despite suppressing procaspase-3 expression, miR-30e was unable to protect RKO colon carcinoma cells from DNA damage-induced death or to induce senescence, as miR-30e completely fails to upregulate p21 in these cells. These data suggest that miR-30e functions in a cell type-dependent manner as an important molecular switch for DNA damage induced stress responses and may thus represent a target of therapeutic value. PMID- 26895379 TI - Tumoral indoleamine 2, 3-dioxygenase 1 is regulated by monocytes and T lymphocytes collaboration in hepatocellular carcinoma. AB - Indoleamine 2, 3-Dioxygenase 1 (IDO1) in cancer cells plays a critical role in tumor immunosuppression. However, the precise mechanisms regulating tumoral IDO1 expression in tumor milieus remain unclear. Here, we reported that IDO1 expression in tumor cells of hepatocelluar carcinomas (HCC), displayed a discrete rather than uniform pattern. In vitro culture, human hepatoma cell lines did not constitutively express IDO1. Interestingly, co-culture with peripheral blood mononuclear cells (PBMC) significantly induced and maintained IDO1 expression in these tumor cells, predominantly through IFN-gamma. Mechanistically, we showed that IDO1 expression in tumor cells was only induced when co-cultured with both T lymphocytes and monocytes. Moreover, the cooperation between T lymphocytes and monocytes played an indispensable role on the tumoral IDO1 expression in immunocompromised mice. Taken together, our data supported the notion that IDO1 expression in tumor cells might serve as a counter-regulatory mechanism regulated by immune system, and provided new insights into the collaborative action of different inflammatory cells in tumor immunosuppression. PMID- 26895381 TI - The scenario-based generalization of radiation therapy margins. AB - We give a scenario-based treatment plan optimization formulation that is equivalent to planning with geometric margins if the scenario doses are calculated using the static dose cloud approximation. If the scenario doses are instead calculated more accurately, then our formulation provides a novel robust planning method that overcomes many of the difficulties associated with previous scenario-based robust planning methods. In particular, our method protects only against uncertainties that can occur in practice, it gives a sharp dose fall-off outside high dose regions, and it avoids underdosage of the target in 'easy' scenarios. The method shares the benefits of the previous scenario-based robust planning methods over geometric margins for applications where the static dose cloud approximation is inaccurate, such as irradiation with few fields and irradiation with ion beams. These properties are demonstrated on a suite of phantom cases planned for treatment with scanned proton beams subject to systematic setup uncertainty. PMID- 26895380 TI - Upregulated WDR26 serves as a scaffold to coordinate PI3K/ AKT pathway-driven breast cancer cell growth, migration, and invasion. AB - The phosphatidylinositol 3-kinase (PI3K)/AKT pathway transmits signals downstream of receptor tyrosine kinases and G protein-coupled receptors (GPCRs), and is one of the most dysregulated pathways in breast cancer. PI3Ks and AKTs consist of multiple isoforms that play distinct and even opposite roles in breast cancer cell growth and metastasis. However, it remains unknown how the activities of various PI3K and AKT isoforms are coordinated during breast cancer progression. Previously, we showed WDR26 is a novel WD40 protein that binds Gbetagamma and promotes Gbetagamma signaling. Here, we demonstrate that WDR26 is overexpressed in highly malignant breast tumor cell lines and human breast cancer samples, and that WDR26 overexpression correlates with shortened survival of breast cancer patients. In highly malignant cell lines (MDA-MB231, DU4475 and BT549), downregulation of WDR26 expression selectively alleviated GPCR- but not EGF receptor-stimulated PI3K/AKT signaling and tumor cell growth, migration and invasion. In contrast, in a less malignant cell line (MCF7), WDR26 overexpression had the opposite effect. Additional studies indicate that downstream of GPCR stimulation, WDR26 serves as a scaffold that fosters assembly of a specific signaling complex consisting of Gbetagamma, PI3Kbeta and AKT2. In an orthotopic xenograft mouse model of breast cancer, disrupting formation of this complex, by overexpressing WDR26 mutants in MDA-MB231 cells, abrogated PI3K/AKT activation and tumor cell growth and metastasis. Together, our results identify a novel mechanism regulating GPCR-dependent activation of the PI3K/AKT signaling axis in breast tumor cells, and pinpoint WDR26 as a potential therapeutic target for breast cancer. PMID- 26895382 TI - MOF-Derived ZnO/Ni3ZnC0.7/C Hybrids Yolk-Shell Microspheres with Excellent Electrochemical Performances for Lithium Ion Batteries. AB - In this study, ZnO/Ni3ZnC0.7/C spheres were synthesized successfully via a simple method based on metal-organic frameworks (MOFs). The experimental results show that the reaction time has a great influence on the structure of the material. ZnO/Ni3ZnC0.7/C spheres with controlled solid and yolk-shell structures have been obtained by altering the reaction time. When applied as anode materials, both the solid and the yolk-shell ZnO/Ni3ZnC0.7/C composites present excellent electrochemical performance. In addition, it is worth mentioning that the yolk shell structure composite's property is superior to that of the solid one's in terms of lithium storage. The stable reversible capacity of yolk-shell ZnO/Ni3ZnC0.7/C can be retained at 1002 mA h g(-1) at 500 mA g(-1) after completion of 750 cycles, and it also exhibits superior rate performance. In contrast, the solid ZnO/Ni3ZnC0.7/C under the same conditions of testing shows a reversible capacity of 824 mA h g(-1). PMID- 26895383 TI - Erratum: Use of low-dose sulodexide in IgA nephropathy patients on renin angiotensin system blockades [Volume 31, Issue 3, September 2012, Pages 163-169]. AB - [This corrects the article DOI: 10.1016/j.krcp.2012.06.006.]. PMID- 26895384 TI - Bisphosphonates: Pharmacokinetics, bioavailability, mechanisms of action, clinical applications in children, and effects on tooth development. AB - Bisphosphonates (BPs) avidly bind to calcium crystals and inhibit osteoclastic bone resorption, making them useful for treatment of skeletal disorders such as osteoporosis, Paget's disease, osteogenesis imperfecta and metastatic bone diseases. BPs therapeutically act by causing toxic effects on osteoclasts or interfering with specific intracellular pathways in those cells. BPs that possess nitrogen in their composition are called nitrogen-containing BPs (NBPs) and include alendronate, pamidronate, risedronate, ibandronate, and zoledronate. Simple BPs or non-NBPs do not have nitrogen in their composition, include etiodronate and clodronate, and were the first to be tested in animals and clinically used. Because BPs may be administered to pregnant women or children during deciduous and permanent teeth development, it is expected that they might disturb tooth eruption and development. A review of current literature on pharmacokinetics, bioavailability, mechanisms of action, and clinical applications of BPs in children, and their effects on tooth eruption and development is presented. PMID- 26895385 TI - Aconitum carmichaelii protects against acetaminophen-induced hepatotoxicity via B cell lymphoma-2 protein-mediated inhibition of mitochondrial dysfunction. AB - We previously reported the clinical profile of processed Aconitum carmichaelii (AC, Aconibal((r))), which included inhibition of cytochrome P450 (CYP) 2E1 activity in healthy male adults. CYP2E1 is recognized as the enzyme that initiates the cascade of events leading to acetaminophen (APAP)-induced toxicity. However, no studies have characterized its role in APAP-induced hepatic injury. Here, we investigated the protective effects of AC on APAP-induced hepatotoxicity via mitochondrial dysfunction. AC (5-500 MUg/mL) significantly inhibited APAP induced reduction of glutathione. In addition, AC decreased mitochondrial membrane potential (Deltapsim) and B-cell lymphoma 2 (Bcl-2)-associated X protein levels (% change 46.63) in mitochondria. Moreover, it increased Bcl-2 (% change 55.39) and cytochrome C levels (% change 38.33) in mitochondria, measured using immunofluorescence or a commercial kit. Furthermore, cell membrane integrity was preserved and nuclear fragmentation inhibited by AC. These results demonstrate that AC protects hepatocytes against APAP-induced toxicity by inhibiting mitochondrial dysfunction. PMID- 26895386 TI - Spatial variations in feeding habits and trophic levels of two small pelagic fish species in the central Mediterranean Sea. AB - Trophic ecology of adults of European sardine (Sardina pilchardus) and anchovy (Engraulis encrasicolus) was examined and compared among various regions of central Mediterranean Sea. Carbon and nitrogen stable isotope analyses (delta(13)C and delta(15)N) were adopted as a tool to determine changes in feeding behaviour of adults of sardines and anchovies. In the study period (summer) a clear geographical pattern was recognized in the isotopic composition of both species, with an increasing trend northward. The highest variations in isotopic signal were linked to the geographical positions of the samples and, especially, between pairs of areas: South Sicily/South Campania and Gulf of Gaeta/South Elba. Higher isotope values were found in the anchovies and sardines caught in northern Tyrrhenian Sea, while lower values were mostly estimated in the southern region. Higher carbon and nitrogen isotopes may reflect a more coastal behaviour of both species, being (13)C-enriched source from benthic primary producers in addition to phytoplankton. Variations in the nitrogen isotope ratio may reflect not only differences in the trophic level of prey species, but also variations in the baseline level of food webs. Our results support the hypothesis that feeding behaviour of both species is directly or indirectly influenced by local factors, or by resource partitioning based on zooplankton size. Findings can supply knowledge needed for improving fish stock management and promoting plans able to take into account also local ecosystem analysis. PMID- 26895388 TI - Substrate-Dependent Mechanistic Divergence in Decarboxylative Heck Reaction at Room Temperature. AB - We report herein a Pd(II)-catalyzed Heck-type coupling between arene carboxylic acids and alkenes at room temperature. Mechanistically, the reaction proceeds in two distinct pathways where electron-rich substrates undergo a palladium(II) catalyzed decarboxylation and electron-deficient substrates proceed through silver(I)-assisted decarboxylation. Dimethyl sulfoxide (DMSO) or sulfide ligands have positive and negative roles in the reaction outcome, respectively. The present protocol is combined for the peptide modification under mild reaction conditions. PMID- 26895387 TI - Conformation-Selective Analogues of Dasatinib Reveal Insight into Kinase Inhibitor Binding and Selectivity. AB - In the kinase field, there are many widely held tenets about conformation selective inhibitors that have yet to be validated using controlled experiments. We have designed, synthesized, and characterized a series of kinase inhibitor analogues of dasatinib, an FDA-approved kinase inhibitor that binds the active conformation. This inhibitor series includes two Type II inhibitors that bind the DFG-out inactive conformation and two inhibitors that bind the alphaC-helix-out inactive conformation. Using this series of compounds, we analyze the impact that conformation-selective inhibitors have on target binding and kinome-wide selectivity. PMID- 26895389 TI - Maternal Plasma DHA Levels Increase Prior to 29 Days Post-LH Surge in Women Undergoing Frozen Embryo Transfer: A Prospective, Observational Study of Human Pregnancy. AB - CONTEXT: Docosahexaenoic acid (DHA) is an important fatty acid required for neurological development but its importance during early fetal neurological organogenesis is unknown. OBJECTIVE: This study aimed to assess plasma fatty acid changes in early pregnancy in women undergoing natural cycle-frozen embryo transfer as a means of achieving accurately timed periconceptual sampling. DESIGN: Women undergoing frozen embryo transfer were recruited and serial fasting blood samples were taken pre-luteinizing hormone (LH) surge, and at 18, 29, and 45 d post-LH surge and fatty acids were analyzed using gas chromatography. SETTING: This study took place at the Assisted Conception Unit, Glasgow Royal Infirmary, Scotland. MAIN OUTCOME MEASURES: Plasma fatty acid concentrations and influence of twin pregnancies on DHA plasma concentration were measured. RESULTS: In pregnant women, there was a rapid, early increase in the maternal rate of change of plasma DHA concentration observed by 29 d post-LH surge (mean +/- SD, from 0.1 +/- 1.3 to 1.6 +/- 2.9 nmol DHA per mL plasma per day). This early pressure to increase plasma DHA concentration was further emphasized in twin pregnancies where the increase in DHA concentration over 45 d was 2-fold higher than in singleton pregnancies (mean +/- SD increase, 74 +/- 39 nmol/mL vs 36 +/- 40 nmol/mL). An index of delta-6 desaturase activity increased 30% and positively correlated with the rate of change of DHA concentration between 18 and 29 d post LH surge (R2 adjusted = 41%; P = .0002). DHA was the only fatty acid with a continual accelerated increase in plasma concentration and a positive incremental area under the curve (mean +/- SD, 632 +/- 911 nmol/mL * d) during the first 45 d of gestation. CONCLUSIONS: An increase in maternal plasma DHA concentration is initiated in human pregnancy prior to neural tube closure which occurs at 28 d gestation. PMID- 26895390 TI - The Relationship Between Parathyroid Hormone and 25-Hydroxyvitamin D During and After Pregnancy. AB - CONTEXT: There is debate about whether women may need greater vitamin D supplementation when pregnant. However, it is unclear whether the 25 hydroxyvitamin D (25-OH-D) concentration required for suppression of PTH (ie, suggesting vitamin D sufficiency) differs between pregnancy and the nongravid state. OBJECTIVE: To systematically characterize the relationship between 25-OH-D and PTH during and after pregnancy. DESIGN/SETTING/PARTICIPANTS: In this study, 468 women underwent serial assessment of serum 25-OH-D and PTH in late pregnancy, at 3 months postpartum, and at 12 months postpartum. At each visit, segmented regression analysis was performed to: 1) determine the best model to fit the relationship between 25-OH-D and PTH; and 2) identify the 25-OH-D threshold above which PTH is maximally suppressed. RESULTS: Serum 25-OH-D and PTH were inversely correlated at each of the pregnancy (r = -0.33; P < .0001), 3 months postpartum (r = -0.37; P < .0001), and 12 months postpartum (r = -0.34; P < .0001) assessments. In pregnancy, PTH first rises when 25-OH-D falls below 82 nmol/L (95% confidence interval, 61-103) and follows a linear relationship with declining 25-OH-D thereafter. In contrast, at both postpartum visits, there was a curvilinear relationship between 25-OH-D and PTH below the 25-OH-D threshold at which PTH is suppressed (71 nmol/L [61-81] at 3 months and 81 nmol/L [61-100] at 12 months). The 25-OH-D thresholds for PTH suppression in pregnancy and at 3 and 12 months postpartum were not significantly different from one another (all pairwise P >= .26). CONCLUSION: Although the shape of the relationship between 25 OH-D and PTH differs between pregnancy and the postpartum, the 25-OH-D thresholds for PTH suppression are similar, supporting comparable targets for vitamin D supplementation. PMID- 26895391 TI - Oriented Mn-doped CuO nanowire arrays. AB - Using anodic aluminum oxide membranes as the nanoreactors and controller, oriented nanowire arrays of the diluted magnetic semiconductor Mn-doped CuO have been successfully fabricated using Mn(NO3)2 . 4H2O and Cu(NO3)2 . 3H2O as the starting materials. X-ray diffraction measurements showed that the as-prepared oriented nanowire arrays are of high purity. Scanning electron microscope and transmission electron microscope studies showed the nanowires are oriented, continuous and uniform with a diameter and length of about 170 nm and several tens of micrometers, respectively, and thus of a high aspect ratio. Low temperature magnetic measurements showed the ferromagnetic property of the oriented Mn-doped CuO nanowire arrays with the critical temperature at around 80 K, which will endow them with great potential applications in spintronics in the future. PMID- 26895392 TI - [Not Available]. PMID- 26895393 TI - A Festschrift to Dr. Albert "Mickey" Stunkard: Celebrating a Lifetime of Obesity and Eating Disorders Research (Born February 7, 1922, New York City; Died July 12, 2014, Bryn Mawr, PA). PMID- 26895395 TI - Exercise Reduces Lung Fibrosis Involving Serotonin/Akt Signaling. AB - PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial pneumonia, which involves aberrant serotonin (5-hydroxytryptamine [5-HT]) and Akt signaling. As protective effects of chronic aerobic training (AT) have been demonstrated in the context of lung injury, this study investigated whether AT attenuates bleomycin-induced lung fibrosis partly via a reduction of 5-HT and AKT signaling. METHODS: Seventy-two C57BL/6 male mice were distributed in Control (Co), Exercise (Ex), Fibrosis (Fi), and Fibrosis + Exercise (Fi + Ex) groups. Bleomycin (1.5 UI.kg) was administered on day 1 and treadmill AT began on day 15 and continued for 60 min.d, 5 d.wk for 4 wk. We evaluated total and differential cell counts in bronchoalveolar lavage (BAL), interleukin (IL)-1beta, IL-6, CXCL1/KC, IL-10, tumor necrosis factor alpha, and transforming growth factor beta levels in BAL, collagen content in lung parenchyma, 5-HT levels in BAL fluid and in serum, the expression of 5-HT2B receptor, and Akt phosphorylation in lung tissue. RESULTS: AT reduced bleomycin-increased number of total cells (P < 0.001), neutrophils (P < 0.01), macrophages (P < 0.01), and lymphocytes (P < 0.05) in BAL. It also reduced the levels of IL-1beta (P < 0.01), IL-6 (P < 0.05), CXCL1/KC (P < 0.001), tumor necrosis factor alpha (P < 0.001), and transforming growth factor beta (P < 0.001). It increased expression of ant-inflammatory cytokine IL-10 (P < 0.001). It reduced bleomycin-increased 5-HT levels in BAL (P < 0.001) and in serum (P < 0.05). Reductions in collagen fiber deposition (P < 0.01), 5-HT2B receptor expression (P < 0.01), and Akt phosphorylation in lung tissue were observed. CONCLUSIONS: AT accelerates the resolution of lung inflammation and fibrosis in a model of bleomycin-induced lung fibrosis partly via attenuation of 5-HT/Akt signaling. PMID- 26895394 TI - Food insecurity, vitamin D insufficiency and respiratory infections among Inuit children. AB - BACKGROUND: Food insecurity, vitamin D deficiency and lower respiratory tract infections are highly prevalent conditions among Inuit children. However, the relationship between these conditions has not been examined in this population. OBJECTIVE: The objective of this study was to examine the relationship between food insecurity and severe respiratory infections before age 2 years and health centre visits for a respiratory problem in the past year. We also explored the relationship between serum vitamin D status and respiratory outcomes in this population. DESIGN: We included children aged 3-5 years who participated in a cross-sectional survey of the health of preschool Inuit children in Nunavut, Canada, from 2007 to 2008 (n=388). Parental reports of severe respiratory infections in the first 2 years of life and health care visits in the past 12 months were assessed through a questionnaire. Child and adult food security were assessed separately and serum 25-hydroxyvitamin D3 levels were measured in a subgroup of participants (n=279). Multivariate logistic regression was performed to assess the association between food security, vitamin D and each of the 2 respiratory outcomes. RESULTS: Child and adult food insecurity measures were not significantly associated with adverse respiratory outcomes. Household crowding [odds ratio (OR)=1.51, 95% confidence interval (CI) 1.09-2.09, p=0.01 for the child food security model] and higher birth weight (OR=1.21, 95% CI: 1.02-1.43, p=0.03) were associated with reported severe chest infections before age 2 years while increasing age was associated with decreased odds of reported health care visits for a respiratory problem (OR=0.66, 95% CI: 0.48-0.91, p=0.02). Neither vitamin D insufficiency nor deficiency was associated with these respiratory outcomes. CONCLUSIONS: Using a large cross-sectional survey of Inuit children, we found that household crowding, but not food security or vitamin D levels, was associated with adverse respiratory outcomes. Further studies are warranted to examine the impact of decreasing household crowding on the respiratory health of these children. PMID- 26895396 TI - Environmental Endocrine Disruptor Affects Voluntary Physical Activity in Mice. AB - INTRODUCTION: Voluntary physical activity levels are regulated by sex hormones. The purpose of this study was to determine the effect of the endocrine disruptor benzyl butyl phthalate (BBP) on the regulation of physical activity in mice. METHODS: Mouse dams were treated with 500 mg.kg.d of BBP or vehicle on gestation days 9-16. Pups were weaned and analyzed for voluntary physical activity levels, puberty development, sex hormone levels, and body composition during the 20-wk period. RESULTS: Seventy-three offspring from BBP-treated dams were studied (n = 43 males and n = 30 females). Endocrine disruption was indicated by decreased anogenital distances in BBP-treated male offspring at 10 (P = 0.001) and 20 wk (P = 0.038) and delayed vaginal openings in BBP-treated female offspring (P = 0.001). Further, there was a significant decrease in serum testosterone concentration in male mice between control and BBP at 10 wk (P = 0.039) and at 20 wk (P = 0.022). In female mice, there was a significant increase in serum testosterone concentration in BBP mice at 20 wk (P = 0.002) and a significant increase in estrogen (estradiol) concentrations at 20 wk in the control female mice (P = 0.015). Overall, BBP mice ran significantly less distance (males, P = 0.008; females, P = 0.042) than controls. Other than a significant increase in BBP-treated males in fat mass at 20 wk (P = 0.040), there was no significant decrease in weight, lean mass, or fat mass in either female or male mice, regardless of treatment. CONCLUSION: Maternal endocrine disruption altered hormone response, but not body composition in either sex of offspring, with a corresponding decreased activity throughout early adulthood in all offspring. These results suggest that exposure to common environmental endocrine disruptors in utero can reduce and alter physical activity levels in offspring. PMID- 26895397 TI - Single-cell proteomics: potential implications for cancer diagnostics. AB - Single-cell proteomics in cancer is evolving and promises to provide more accurate diagnoses based on detailed molecular features of cells within tumors. This review focuses on technologies that allow for collection of complex data from single cells, but also highlights methods that are adaptable to routine cancer diagnostics. Current diagnostics rely on histopathological analysis, complemented by mutational detection and clinical imaging. Though crucial, the information gained is often not directly transferable to defined therapeutic strategies, and predicting therapy response in a patient is difficult. In cancer, cellular states revealed through perturbed intracellular signaling pathways can identify functional mutations recurrent in cancer subsets. Single-cell proteomics remains to be validated in clinical trials where serial samples before and during treatment can reveal excessive clonal evolution and therapy failure; its use in clinical trials is anticipated to ignite a diagnostic revolution that will better align diagnostics with the current biological understanding of cancer. PMID- 26895399 TI - Feasibility of a metamagnetic transition in correlated systems. AB - The long-standing issue of the competition between the magnetic field and the Kondo effect, favoring, respectively, triplet and singlet ground states, is addressed using a cluster slave-rotor mean-field theory for the Hubbard model and its spin-correlated, spin-frustrated extensions in two dimensions. The metamagnetic jump is established and compared with earlier results of dynamical mean-field theory. This approach also reproduces the emergent super-exchange energy scale in the insulating side. A scaling is found for the critical Zeeman field in terms of the intrinsic coherence scale just below the metal-insulator transition, where the critical spin fluctuations are soft. The conditions required for metamagnetism to appear at a reasonable field are also underlined. Gutzwiller analysis on the two-dimensional Hubbard model and a quantum Monte Carlo calculation on the Heisenberg spin system are performed to check the limiting cases of the cluster slave-rotor results for the Hubbard model. Low field scaling features for magnetization are discussed. PMID- 26895398 TI - The VITRO Score (Von Willebrand Factor Antigen/Thrombocyte Ratio) as a New Marker for Clinically Significant Portal Hypertension in Comparison to Other Non Invasive Parameters of Fibrosis Including ELF Test. AB - BACKGROUND: Clinically significant portal hypertension (CSPH), defined as hepatic venous pressure gradient (HVPG) >=10 mmHg, causes major complications. HVPG is not always available, so a non-invasive tool to diagnose CSPH would be useful. VWF-Ag can be used to diagnose. Using the VITRO score (the VWF-Ag/platelet ratio) instead of VWF-Ag itself improves the diagnostic accuracy of detecting cirrhosis/ fibrosis in HCV patients. AIM: This study tested the diagnostic accuracy of VITRO score detecting CSPH compared to HVPG measurement. METHODS: All patients underwent HVPG testing and were categorised as CSPH or no CSPH. The following patient data were determined: CPS, D'Amico stage, VITRO score, APRI and transient elastography (TE). RESULTS: The analysis included 236 patients; 170 (72%) were male, and the median age was 57.9 (35.2-76.3; 95% CI). Disease aetiology included ALD (39.4%), HCV (23.4%), NASH (12.3%), other (8.1%) and unknown (11.9%). The CPS showed 140 patients (59.3%) with CPS A; 56 (23.7%) with CPS B; and 18 (7.6%) with CPS C. 136 patients (57.6%) had compensated and 100 (42.4%) had decompensated cirrhosis; 83.9% had HVPG >=10 mmHg. The VWF-Ag and the VITRO score increased significantly with worsening HVPG categories (P<0.0001). ROC analysis was performed for the detection of CSPH and showed AUC values of 0.92 for TE, 0.86 for VITRO score, 0.79 for VWF-Ag, 0.68 for ELF and 0.62 for APRI. CONCLUSION: The VITRO score is an easy way to diagnose CSPH independently of CPS in routine clinical work and may improve the management of patients with cirrhosis. PMID- 26895400 TI - Prevalence of job-related distress and satisfaction in a nationwide cardiology setting: The IANUS - itAliaN cardiologists' Undetected distress Study. AB - INTRODUCTION AND OBJECTIVES: Cardiologists' work distress has been seldom studied. The ItAliaN cardiologists' Undetected distress Study survey was designed to assess prevalence of work distress and satisfaction, and to gain insight into associations among these constructs and socio-demographics and job description. METHODS: We invited members of our national cardiological society (Associazione Nazionale Medici Cardiologi Ospedalieri) to participate in an anonymous, self report, exclusively web-based survey, posted on the Associazione Nazionale Medici Cardiologi Ospedalieri website. ItAliaN cardiologists' Undetected distress Study included socio-demographics, job description and a 15-item questionnaire on job related distress and work satisfaction. RESULTS: Of 7393 invited cardiologists, 1064 completed the survey. Organizational problems and worries about medico-legal controversies were reported by 71% and 49% of participants, respectively; over one-third reported loss of enthusiasm, helplessness, work-life imbalance and lack of control over work. Conversely, 86% felt competent at work, 67% rewarded by the moral/human meaning of their work and 52% satisfied with their professional fulfilment. Factor analysis revealed a meaningful underlying structure including four factors: job strain, positive meaning, emotional fatigue and relational difficulties. Relational difficulties were more frequent in cardiologists working in primary-level than in secondary and tertiary care hospitals (P = 0.017 and P = 0.013, respectively). Interventional cardiologists reported higher positive meaning than those in the clinical inpatients area and outpatient diagnostic settings (P = 0.007 and P = 0.025, respectively) and lower emotional fatigue than subjects in the clinical inpatients area (P = 0.0005). CONCLUSION: Cardiologists' work distress should be interpreted integrating job-related negative aspects with a reappraisal of protective personal and relational resources, which should be fostered to promote physicians' wellbeing at the individual, collective and organizational levels. PMID- 26895402 TI - Atrial fibrillation, cognitive impairment, frailty and disability in older heart failure patients. AB - BACKGROUND: Aim of the study was to prospectively assess the relation between atrial fibrillation, cognitive impairment, frailty and disability in older patients with chronic heart failure . METHODS: Three hundred thirty-one ambulatory community-living patients aged 70 years and older (mean 78 +/- 6; range 70-93; 43% women) in stable conditions and optimized therapy were enrolled in seven heart failure cardiology clinics. Cognitive impairment was defined by a corrected Mini Mental State Examination score less than 24. Gait speed was used as marker of frailty and measured on a 4 m distance at usual pace. RESULTS: Ninety-eight patients (30%) were on atrial fibrillation at enrolment and 20 (6%) had a history of paroxysmal/persistent atrial fibrillation. Patients with atrial fibrillation were more frequently women with severe valvular disease, preserved left ventricular ejection fraction and less frequently on beta-blockers. At multivariable analyses, atrial fibrillation emerged as independently related to cognitive impairment [odds ratio (OR) 1.909 (1.072-3.397); P = 0.028], as well as to reduced gait speed [OR 4.366 (2.104-9.060); P < 0.001]. Furthermore, atrial fibrillation was significantly associated with disability in either basic or instrumental activities of daily living. No differences were found in mortality and morbidity. CONCLUSION: Among patients with chronic heart failure, those with atrial fibrillation present a high prevalence of frailty, cognitive impairment and disability. The hypothetical mechanisms by which atrial fibrillation and heart failure may affect these conditions are multiple and further studies are warranted. However, screening for these variables in clinical practice is simple and inexpensive and may allow better strategies for intervention in this high risk population. PMID- 26895403 TI - Preliminary Evaluation of Acoustic Radiation Force Impulse Shear Wave Imaging to Detect Hepatic Fibrosis in Morbidly Obese Patients Before Bariatric Surgery. AB - BACKGROUND AND AIMS: Acoustic Radiation Force Impulse (ARFI) shear wave imaging is a noninvasive method of assessment of the liver to detect fibrosis in patients with chronic hepatitis and nonalcoholic fatty liver disease (NAFLD). The aim of this retrospective study was to investigate whether noninvasive measurement of shear wave velocity (SWV) by ARFI shear wave imaging has a potential usefulness for detection of fibrosis secondary to NAFLD in patients with morbid obesity. METHODS: Twenty-eight morbidly obese patients were included in this study. NAFLD and fibrosis were classified according to the nonalcoholic steatohepatitis (NASH) Clinical Research Network NAFLD activity score. SWV was quantified by ARFI imaging. Component steatosis, inflammation and ballooning scores, and fibrosis staging were correlated with SWV, and diagnostic accuracy of ARFI for fibrosis was assessed. RESULTS: There was a decrease in mean SWV with increasing hepatic steatosis (P = .057). The SWV showed a significant negative correlation (r = 0.417, P = .011) with steatosis grade. The mean SWV was neither significantly different nor correlating with the obesity classes based on body mass index (BMI), steatosis grades, inflammation grades, ballooning grades, and fibrosis stages of NAFLD. Receiver operating characteristic analysis showed no significant area under curve for diagnosis of fibrosis using SWV. Valid SWV could be acquired in all subjects; however, only 21.42% fulfilled the interquartile range criterion. CONCLUSION: ARFI SWV values do not correlate with fibrosis on liver biopsy in morbidly obese patients and lack accuracy for diagnosis. Discordant values may be related to higher BMI and increasing hepatic steatosis. PMID- 26895401 TI - Improving the appropriateness of sudden arrhythmic death primary prevention by implantable cardioverter-defibrillator therapy in patients with low left ventricular ejection fraction. Point of view. AB - It is generally accepted that the current guidelines for the primary prevention of sudden arrhythmic death, which are based on ejection fraction, do not allow the optimal selection of patients with low left ventricular ejection fraction of ischemic and nonischemic etiology for implantation of a cardioverter defibrillator. Ejection fraction alone is limited in both sensitivity and specificity. An analysis of the risk of sudden arrhythmic death with a combination of multiple tests (ejection fraction associated with one or more arrhythmic risk markers) could partially compensate for these limitations. We propose a polyparametric approach for defining the risk of sudden arrhythmic death using ejection fraction in combination with other clinical and arrhythmic risk markers (i.e. late gadolinium enhancement cardiac magnetic resonance, T-wave alternans, programmed ventricular stimulation, autonomic tone, and genetic testing) that have been validated in nonrandomized trials. In this article, we examine these approaches to identify three subsets of patients who cannot be comprehensively assessed by the current guidelines: patients with ejection fraction of 35% or less and a relatively low risk of sudden arrhythmic death despite the ejection fraction value; patients with ejection fraction of 35% or less and high competitive risk of death due to evolution of heart failure or noncardiac causes; and patients with ejection fraction between 35 and 45% with relatively high risk of sudden arrhythmic death despite the ejection fraction value. PMID- 26895404 TI - Mechanogeneration of Acid from Oxime Sulfonates. AB - The generation of acid under mechanical force is potentially useful for initiating proton-catalyzed changes in polymeric materials. Here we demonstrate that oxime sulfonates-known photoacid generators-are also acid generators when activated mechanically. NMR analysis of products suggests that the ultrasound induced mechanochemical scission of the oxime sulfonate mechanophore also generates a ketone functional moiety, in addition to acid. Both acid and ketone moieties are useful for developing stress-responsive polymeric materials for autonomous self-healing applications. PMID- 26895405 TI - Next-Generation Sequencing of a Single Domain Antibody Repertoire Reveals Quality of Phage Display Selected Candidates. AB - Next-Generation Sequencing and bioinformatics are powerful tools for analyzing the large number of DNA sequences present in an immune library. In this work, we constructed a cDNA library of single domain antibodies from a llama immunized with staphylococcal enterotoxin B. The resulting library was sequenced, resulting in approximately 8.5 million sequences with 5.4 million representing intact, useful sequences. The sequenced library was interrogated using sequences of known SEB-binding single domain antibodies from the library obtained through phage display panning methods in a previous study. New antibodies were identified, produced, and characterized, and were shown to have affinities and melting temperatures comparable to those obtained by traditional panning methods. This demonstrates the utility of using NGS as a complementary tool to phage-displayed biopanning as a means for rapidly obtaining additional antibodies from an immune library. It also shows that phage display, using a library of high diversity, is able to select high quality antibodies even when they are low in frequency. PMID- 26895407 TI - Stool bacterial load in preterm infants with necrotising enterocolitis. AB - Resected gut tissue in necrotising enterocolitis (NEC) has a higher bacterial load than controls. Quantitative PCR was performed on longitudinal NEC and control stool samples (n=72). No significant difference in the total bacterial load was found between samples at diagnosis compared to controls or temporally within NEC. PMID- 26895406 TI - The importance of cardiovascular pathology contributing to maternal death: Confidential Enquiry into Maternal Deaths in South Africa, 2011-2013. AB - AIMS: Cardiac disease is emerging as an important contributor to maternal deaths in both lower-to-middle and higherincome countries. There has been a steady increase in the overall institutional maternal mortality rate in South Africa over the last decade. The objectives of this study were to determine the cardiovascular causes and contributing factors of maternal death in South Africa, and identify avoidable factors, and thus improve the quality of care provided. METHODS: Data collected via the South African National Confidential Enquiry into Maternal Deaths (NCCEMD) for the period 2011-2013 for cardiovascular disease (CVD) reported as the primary pathology was analysed. Only data for maternal deaths within 42 days post-delivery were recorded, as per statutory requirement. One hundred and sixty-nine cases were reported for this period, with 118 complete hospital case files available for assessment and data analysis. RESULTS: Peripartum cardiomyopathy (PPCM) (34%) and complications of rheumatic heart disease (RHD) (25.3%) were the most important causes of maternal death. Hypertensive disorders of pregnancy, HIV disease infection and anaemia were important contributing factors identified in women who died of peripartum cardiomyopathy. Mitral stenosis was the most important contributor to death in RHD cases. Of children born alive, 71.8% were born preterm and 64.5% had low birth weight. Seventy-eight per cent of patients received antenatal care, however only 33.7% had a specialist as an antenatal care provider. Avoidable factors contributing to death included delay in patients seeking help (41.5%), lack of expertise of medical staff managing the case (29.7%), delay in referral to the appropriate level of care (26.3%), and delay in appropriate action (36.4%). CONCLUSION: The pattern of CVD contributing to maternal death in South Africa was dominated by PPCM and complications of RHD, which could, to a large extent, have been avoided. It is likely that there were many CVD deaths that were not reported, such as late maternal mortality (up to one year postpartum). Infrastructural changes, use of appropriate referral algorithm and training of primary, secondary and tertiary staff in CVD complicating pregnancy is likely to improve the outcome. The use of simple screening equipment and point-of-care testing for early-onset heart failure should be explored via research projects. PMID- 26895408 TI - The conundrum of nucleated red blood cells in premature infants. PMID- 26895411 TI - Malcolm H. Chisholm (1945-2015). AB - Malcolm H. Chisholm, Distinguished Professor of Mathematical and Physical Sciences at The Ohio State University, passed away on November 20, 2015. He is best known for his pioneering work on the chemistry of metal-metal multiple bonds, the molecular and electronic structure and bonding of transition-metal compounds, and the exploration of excited states of complexes with metal-metal quadruple bonds. PMID- 26895409 TI - Pimaradienoic Acid Inhibits Carrageenan-Induced Inflammatory Leukocyte Recruitment and Edema in Mice: Inhibition of Oxidative Stress, Nitric Oxide and Cytokine Production. AB - Pimaradienoic acid (PA; ent-pimara-8(14),15-dien-19-oic acid) is a pimarane diterpene found in plants such as Vigueira arenaria Baker (Asteraceae) in the Brazilian savannas. Although there is evidence on the analgesic and in vitro inhibition of inflammatory signaling pathways, and paw edema by PA, its anti inflammatory effect deserves further investigation. Thus, the objective of present study was to investigate the anti-inflammatory effect of PA in carrageenan-induced peritoneal and paw inflammation in mice. Firstly, we assessed the effect of PA in carrageenan-induced leukocyte recruitment in the peritoneal cavity and paw edema and myeloperoxidase activity. Next, we investigated the mechanisms involved in the anti-inflammatory effect of PA. The effect of PA on carrageenan-induced oxidative stress in the paw skin and peritoneal cavity was assessed. We also tested the effect of PA on nitric oxide, superoxide anion, and inflammatory cytokine production in the peritoneal cavity. PA inhibited carrageenan-induced recruitment of total leukocytes and neutrophils to the peritoneal cavity in a dose-dependent manner. PA also inhibited carrageenan induced paw edema and myeloperoxidase activity in the paw skin. The anti inflammatory mechanism of PA depended on maintaining paw skin antioxidant activity as observed by the levels of reduced glutathione, ability to scavenge the ABTS cation and reduce iron as well as by the inhibition of superoxide anion and nitric oxide production in the peritoneal cavity. Furthermore, PA inhibited carrageenan-induced peritoneal production of inflammatory cytokines TNF-alpha and IL-1beta. PA presents prominent anti-inflammatory effect in carrageenan-induced inflammation by reducing oxidative stress, nitric oxide, and cytokine production. Therefore, it seems to be a promising anti-inflammatory molecule that merits further investigation. PMID- 26895412 TI - An Abundance of Selves: Young Adults' Narrative Identities While Living With Cancer. AB - BACKGROUND: Identity negotiations of people living with cancer have been shown to be significant psychosocial challenges throughout cancer trajectories but have not been adequately explored among young adults with cancer. Narrative approaches might help to reveal moments of (dis)empowerment that affect their identity negotiations. OBJECTIVE: The aim of this study is to explore how young adults speak to their identities in relation to their narratives of having cancer and receiving care. METHODS: A total of 21 young adults (18-45 years old) provided cancer narratives through semistructured life history interviews. Thematic narrative analysis was used to determine how participants represented themselves in their stories. RESULTS: Participants used a wide diversity of identities well beyond those most familiar in dominant discourses (eg, patients, survivors, and fighters), and their identities frequently changed at significant "turning points" in their narratives, especially in relation to good and bad experiences of care. CONCLUSIONS: Cancer-related identities often undergo personal and social negotiation over time, and not just among young adults still feeling the effects of treatment. Psychosocial oncology could take further steps toward incorporating this fluidity and multiplicity within the discipline's discourses of identity. IMPLICATIONS FOR PRACTICE: The identities gathered here may contribute to a more comprehensive toolkit of narrative resources for empowering young adults (and others) with cancer, serving as a starting point for negotiating identities with their care providers. Our findings raise questions about which identities should be fostered and how healthcare professionals might be (unknowingly) involved in patients' identity negotiations. PMID- 26895414 TI - Chemotherapy-Induced Nausea and Vomiting in Women With Gynecological Cancer: A Preliminary Single-Center Study Investigating Medical and Psychosocial Risk Factors. AB - BACKGROUND: Chemotherapy is the treatment of choice for many gynecological tumors, but cytotoxic drugs lead to a wide range of stressful side effects; nausea and vomiting are 2 of the most common and distressing consequences of many chemotherapy regimens. OBJECTIVE: The aim of this study is to investigate various risk factors that could influence the experience of nausea and vomiting after the first chemotherapeutic infusion. METHODS: Women treated for various gynecological cancers (n = 94) took part in the study. Pharmacological and personal risk factors in the development of chemotherapy-induced nausea and vomiting (CINV) were assessed with the use of the State-Trait Anxiety Inventory and a self-report questionnaire. Regression analyses (both univariate and multiple) were performed to establish risk factors associated with CINV. RESULTS: The study highlights the importance of working status (being involved in a working activity during treatment) as a protective factor for developing chemotherapy-induced nausea. Furthermore, younger age, levels of state anxiety, chemotherapy-induced nausea in previous treatments, and alcohol intake were found to have an effect on CINV, increasing its risk. Emetogenic potential was associated only with the presence of delayed vomiting. CONCLUSIONS: Although this is a preliminary study into the risk factors of CINV in gynecological tumors, these findings offer support that personal risk factors contribute to individual differences in the frequency and severity of CINV. IMPLICATIONS FOR PRACTICE: Personal factors should be taken into consideration by the multidisciplinary treating team in gynecology. PMID- 26895413 TI - A Review of the Literature on Multiple Co-occurring Symptoms in Patients With Colorectal Cancer Who Received Chemotherapy Alone or Chemotherapy With Targeted Therapies. AB - BACKGROUND: Patients with colorectal cancer (CRC) rarely experience a single symptom associated with their disease and its treatment. OBJECTIVE: Purpose of this literature review was to summarize the current state of knowledge of multiple co-occurring symptoms in CRC patients who received chemotherapy (CTX) alone or CTX with targeted therapies. METHODS: Comprehensive literature search was conducted from 1990 to 2014. These studies were evaluated in terms of the occurrence of multiple co-occurring symptoms in CRC patients who received CTX alone or CTX with targeted therapies; the most common symptom assessment and quality of life (QOL) instruments used; and the associations identified between select demographic and treatment characteristics, QOL, and multiple co-occurring symptoms. RESULTS: Only 5 studies met this review's inclusion criteria. Two studies compared symptoms in patients who received CTX alone or CTX with targeted therapies, and only 1 study reported on symptom occurrence. Of the 5 studies identified, only 2 used the same instrument to assess symptoms, and only 2 studies evaluated for associations between demographic and treatment characteristics and symptom burden, as well as QOL outcomes. CONCLUSIONS: Given the larger number of patients with CRC, as well as the increased number of CRC patients who will receive targeted therapies with or without CTX, future studies need to describe the occurrence, severity, and distress of multiple co-occurring symptoms and their impact on CRC patients' QOL. IMPLICATIONS FOR PRACTICE: To deliver effective symptom management interventions, the most common, severe, and distressing symptoms that CRC patients experience need to be identified. PMID- 26895415 TI - Validity and Reliability of the Taiwanese Version of the General Fatigue Scale in Cancer Patients. AB - BACKGROUND: Fatigue has been described as the most frequent and distressing problem of cancer patients undergoing chemotherapy. OBJECTIVE: The aim of this study is to evaluate the validity and reliability of the Taiwanese version of the General Fatigue Scale (GFS-T) and to evaluate the severity of the fatigue among breast cancer patients in Taiwan. METHODS: A cross-sectional research design was used, recruiting breast cancer patients from 2 medical centers in Taiwan. Patients completed the scale exploring their GFS-T, the Brief Fatigue Inventory Taiwan Form, and the Eastern Cooperative Oncology Group Performance Status. The data were collected between the day before the first chemotherapy (T1) and 1 week after the first chemotherapy (T2). RESULTS: A total of 171 patients participated in this study. Cronbach's alpha for the GFS-T at both time points both were .94. Factor analysis generated 1 factor that accounted for 73.7% of variance in participants' fatigue. The receiver operating characteristic curve analyses suggested that the GFS-T cut-point of 24 had an adequate combination of sensitivity and specificity to distinguish high and low performance status. The receiver operating characteristic curve is 0.67 (95% confidence interval, 0.59 0.75). CONCLUSIONS: The GFS-T is a reliable and valid instrument for assessing fatigue among cancer patients. Further research is needed to better understand predictors of cancer-related fatigue. IMPLICATIONS FOR PRACTICE: The GFS-T can provide clinical nurses with a useful measure to assess fatigue in cancer patients. PMID- 26895416 TI - Exploratory Factor Analysis of the Strength of the Cultural Affiliation Scale. AB - BACKGROUND: Within the United States, there are individuals who retain the traditions and beliefs of cultural groups that vary from the general majority population. Both healthcare providers and researchers have reported that many individuals who live in but are less affiliated with the dominant culture tend to have less positive health outcomes. OBJECTIVE: The purpose of this study is to use factor analysis to assess the psychometric properties of Mood's 18-item Strength of Cultural Affiliation Scale (SCAS). METHODS: The SCAS was administered to 604 participants from a randomized clinical trial of cancer patients who were treated with radiotherapy at a large central city hospital located in the Midwest. RESULTS: Confirmatory Factor Analyses using Principal Component Analysis with Oblimin Rotation indicated a 16-item, 4-factor final solution with the following subscales: factor 1, lifestyle (7 items); factor 2, language and cultural-specific holidays (3 items); factor 3, relationships (4 items); and factor 4, cultural health practices (2 items). CONCLUSION: The SCAS demonstrated high reliability and content, construct, discriminant, convergent, divergent, and predictive validity. IMPLICATIONS FOR PRACTICE: The SCAS seems to be a reliable and valid tool for practitioners to use to assess a patient's strength of cultural affiliation to provide the best culturally sensitive care possible for the patient. PMID- 26895417 TI - Assessment of Treg/Th17 axis role in immunopathogenesis of chronic injuries of mustard lung disease. AB - PURPOSE: Sulfur mustard (SM) lung is a heterogeneous disease associated with abnormal inflammatory immune responses. The Th17/Treg axis imbalance is associated with the pathogenesis of chronic inflammatory pulmonary disease. We aimed to determine the distribution of different Th17 and Treg cells in patients with SM lung and chronic obstructive pulmonary disease (COPD) and evaluate the clinical implications in this homeostasis. METHODS: In this analytical cross sectional study, CD4 (+) Foxp3(+ )Treg and CD4(+) IL-17(+ )Th17 cells were measured in peripheral blood mononuclear cells (PBMCs) and transbronchial biopsy (TBB) samples of 15 SM-exposed patients, 12 COPD and 13 healthy controls (HCs). The potential correlation between the ratio of Th17/Tregs and lung function was evaluated with multivariate logistic regression (MLR) analysis. RESULTS: The frequency of CD4 (+) FoxP3(+) Tregs and CD4 (+) IL-17(+) Th17 was increased ~1.7 fold (8.71/4.95) and ~2.7-fold (1.028/0.371) respectively, in the PBMC of SM patients compared with the health controls (p < 0.001). The results indicated that there were increases in the frequency of Th17 and Tregs cells in the patients with COPD versus the HC, that is, ~2.6-fold (0.987/0.371) and ~1.4-fold (7.12/4.95), respectively; but they did not reach to SM level (p >= 0.05). Moreover, in the TBB samples, the CD4 (+) IL-17(+ )Th17 and CD4(+) FoxP3(+ )Tregs numbers were significantly higher in SM and COPD patients than HC (p < 0.05). The Th17 and Treg cells were inversely correlated with forced expiratory volume in 1s (FEV1%) (r = -0.351, p = 0.001; r = -0.344, p = 0.021) and FEV1/FVC (r = -0.44, p = 0.001; r = -0.302, p = 0.011), respectively. Instead, positive correlations were found between Treg/Th17 ratios and forced FEV1%pred (r = 0.156, p = 0.007), as well as FEV1/FVC ratio (r = 0.334, p = 0.006). CONCLUSIONS: The imbalance of Th17/Treg has a key role in immunopathogenesis of chronic phase of mustard lung disease. PMID- 26895418 TI - Healthcare students' experiences of an interprofessional, student-led neuro rehabilitation community-based clinic. AB - Student-led clinics are becoming more prominent as educators seek alternate models of clinical education for health professionals. The purpose of this study was to evaluate healthcare students' experiences of an interprofessional student led clinic for clients with neurological conditions. Thirteen students representing occupational therapy, physiotherapy, and speech pathology were recruited for the study. A sequential mixed-methods evaluation was employed and the results from the Interprofessional Education Scale and focus group revealed that the students experienced positive perceptions of working collaboratively with other professions, forming good relationships with others, as well as an increased respect for the roles of other professions. The findings suggest that providing a capstone opportunity, where students can work as part of an interprofessional team with a real client, in a format they may come across in future clinical practice, may be beneficial in providing them with essential interprofessional skills as new graduate health professionals. PMID- 26895419 TI - Out of Pocket Expenditure for Hospitalization among Below Poverty Line Households in District Solan, Himachal Pradesh, India, 2013. AB - INTRODUCTION: Health insurance schemes, like Rashtriya Swasthya Bima Yojana (RSBY), should provide financial protection against catastrophic health costs by reducing out of pocket expenditure (OOPE) for hospitalizations. We estimated and compared the proportion and extent of OOPE among below poverty line (BPL) families beneficiaries and not beneficiaries by RSBY during hospitalizations in district Solan, H.P., India, 2013. METHODS: We conducted a cross sectional survey among hospitalized BPL families in the beneficiaries and non-beneficiaries groups. We compared proportion incurring OOPE and its extent during hospitalization, pre/post-hospitalization periods in different domains. RESULTS: Overall, proportion of non-beneficiaries who incurred OOPE was higher than the beneficiaries but it was not statistically significant (87.2% vs. 80.9%). The median overall OOPE was $39 (Rs 2567) in the non-beneficiaries group as compared to $11 (Rs 713) in the beneficiaries group (p<0.01). Median expenditure on in house and out house drugs and consumables was $23 (Rs 1500) in the non beneficiaries group as compared to nil in the beneficiaries group (p<0.01). Non beneficiary status was significantly associated [OR: 2.4 (1.3-4.3)] with OOPE above median independently and also after adjusting for various covariates. CONCLUSION: RSBY has decreased the extent of OOPE among the beneficiaries; however OOPE was incurred mainly due to purchase of drugs from outside the health facility. The treatment seeking behaviour in beneficiaries group has improved among comparatively older group with chronic conditions. RSBY has enabled beneficiaries to get more facilities such as drugs, consumables and diagnostics from the health facility. PMID- 26895420 TI - Magic Acts with the Cohesin Ring. AB - Recent studies, including two in this issue of Molecular Cell (Elbatsh et al., 2016; Beckouet et al., 2016), cast light on how cohesin regulators harness the energy of ATP hydrolysis to open the cohesin ring and enable dynamic, regulated entrapment of chromosomes. PMID- 26895422 TI - Response to Burgers et al. PMID- 26895421 TI - Who Is Leading the Replication Fork, Pol epsilon or Pol delta? PMID- 26895423 TI - RNA Processing and Genome Stability: Cause and Consequence. AB - It is emerging that the pathways that process newly transcribed RNA molecules also regulate the response to DNA damage at multiple levels. Here, we discuss recent insights into how RNA processing pathways participate in DNA damage recognition, signaling, and repair, selectively influence the expression of genome-stabilizing proteins, and resolve deleterious DNA/RNA hybrids (R-loops) formed during transcription and RNA processing. The importance of these pathways for the DNA damage response (DDR) is underscored by the growing appreciation that defects in these regulatory connections may be connected to the genome instability involved in several human diseases, including cancer. PMID- 26895424 TI - PARP1 Links CHD2-Mediated Chromatin Expansion and H3.3 Deposition to DNA Repair by Non-homologous End-Joining. AB - The response to DNA double-strand breaks (DSBs) requires alterations in chromatin structure to promote the assembly of repair complexes on broken chromosomes. Non homologous end-joining (NHEJ) is the dominant DSB repair pathway in human cells, but our understanding of how it operates in chromatin is limited. Here, we define a mechanism that plays a crucial role in regulating NHEJ in chromatin. This mechanism is initiated by DNA damage-associated poly(ADP-ribose) polymerase 1 (PARP1), which recruits the chromatin remodeler CHD2 through a poly(ADP-ribose) binding domain. CHD2 in turn triggers rapid chromatin expansion and the deposition of histone variant H3.3 at sites of DNA damage. Importantly, we find that PARP1, CHD2, and H3.3 regulate the assembly of NHEJ complexes at broken chromosomes to promote efficient DNA repair. Together, these findings reveal a PARP1-dependent process that couples ATP-dependent chromatin remodeling with histone variant deposition at DSBs to facilitate NHEJ and safeguard genomic stability. PMID- 26895425 TI - Releasing Activity Disengages Cohesin's Smc3/Scc1 Interface in a Process Blocked by Acetylation. AB - Sister chromatid cohesion conferred by entrapment of sister DNAs within a tripartite ring formed between cohesin's Scc1, Smc1, and Smc3 subunits is created during S and destroyed at anaphase through Scc1 cleavage by separase. Cohesin's association with chromosomes is controlled by opposing activities: loading by Scc2/4 complex and release by a separase-independent releasing activity as well as by cleavage. Coentrapment of sister DNAs at replication is accompanied by acetylation of Smc3 by Eco1, which blocks releasing activity and ensures that sisters remain connected. Because fusion of Smc3 to Scc1 prevents release and bypasses the requirement for Eco1, we suggested that release is mediated by disengagement of the Smc3/Scc1 interface. We show that mutations capable of bypassing Eco1 in Smc1, Smc3, Scc1, Wapl, Pds5, and Scc3 subunits reduce dissociation of N-terminal cleavage fragments of Scc1 (NScc1) from Smc3. This process involves interaction between Smc ATPase heads and is inhibited by Smc3 acetylation. PMID- 26895427 TI - Multiple Coexisting Dirac Surface States in Three-Dimensional Topological Insulator PbBi6Te10. AB - By means of angle-resolved photoemission spectroscopy (ARPES) measurements, we unveil the electronic band structure of three-dimensional PbBi6Te10 topological insulator. ARPES investigations evidence multiple coexisting Dirac surface states at the zone-center of the reciprocal space, displaying distinct electronic band dispersion, different constant energy contours, and Dirac point energies. We also provide evidence of Rashba-like split states close to the Fermi level, and deeper M- and V-shaped bands coexisting with the topological surface states. The experimental findings are in agreement with scanning tunneling microscopy measurements revealing different surface terminations according to the crystal structure of PbBi6Te10. Our experimental results are supported by density functional theory calculations predicting multiple topological surface states according to different surface cleavage planes. PMID- 26895428 TI - Implication of nitric oxide (NO) in excess element-induced morphogenic responses of the root system. AB - Extremes of metal and non-metal elements in the soils create a stressful environment and plants exposed to sub-lethal abiotic stress conditions show a broad range of morphogenic responses designated as stress-induced morphogenic response (SIMR). Being the first plant organ directly contacting with elevated doses of elements, the root system shows remarkable symptoms and deserves special attention. In the signalling of root SIMR, the involvement of phytohormones (especially auxin) and reactive oxygen species (ROS) has been earlier suggested. Emerging evidence supports that nitric oxide (NO) and related molecules (reactive nitrogen species, RNS) are integral signals of root system development, and they are active components of heavy metal-induced stress responses as well. Based on these, the main scope of this review is to demonstrate the contribution of NO/RNS to the emergence of excess element-induced root morphogenic responses. The SIMR like root system of lead-treated Arabidopsis thaliana contained elevated NO levels compared to the root not showing SIMR. In NO-deficient nia1nia2 plants, the degree of selenium-induced root SIMR was, in some characteristics altered compared to the wild-type. Moreover, among the molecular elements of SIMR several potential candidates of NO-dependent S-nitrosylation or tyrosine nitration have been found using computational prediction. The demonstrated literature data together with own experimental results strongly outline that NO/RNS are regulating signals in the development of root SIMR in case of excess metal and non-metal elements. This also reveals a new role of NO in acclimation emphasizing its importance in defence mechanisms against abiotic stresses. PMID- 26895429 TI - Aluminum induced metabolic responses in two tea cultivars. AB - Tea [Camellia sinensis (L.)], is an aluminum (Al(3+)) hyperaccumulator plant and grows well in acid soils. In the present study, roots of two tea cultivars, JHC and YS were treated with different concentrations of Al(3+). After treatments, the root length, dry matter, root activity and chlorophyll content (SPAD value) of JHC had greater increase than that of YS. We also detected metabolic changes of two varieties using GC-MS method. Comparison between two cultivars indicated that shikimic pathway was more enhanced in YS roots by Al(3+) with higher levels of catechine, quinic acid and shikimic acid. While, more active amino acid synthesis was found in JHC roots and JHC leaves remained the higher level contents of metabolites related to cysteine synthesis. The comparison also showed that a large amount of sugar alcohols were accumulated in roots of two varieties, whereas most of them were reduced in YS leaves. Other well-known ligands, such as phosphoric acid and malic acid were observed in two cultivars that showed significantly altered abundances under Al(3+) treatments. The results indicated that Al(3+) adaptation of two cultivars may be correlated with their differential metabolism of amino acids, sugars and shikimic acids. PMID- 26895426 TI - Cohesin Releases DNA through Asymmetric ATPase-Driven Ring Opening. AB - Cohesin stably holds together the sister chromatids from S phase until mitosis. To do so, cohesin must be protected against its cellular antagonist Wapl. Eco1 acetylates cohesin's Smc3 subunit, which locks together the sister DNAs. We used yeast genetics to dissect how Wapl drives cohesin from chromatin and identified mutants of cohesin that are impaired in ATPase activity but remarkably confer robust cohesion that bypasses the need for the cohesin protectors Eco1 in yeast and Sororin in human cells. We uncover a functional asymmetry within the heart of cohesin's highly conserved ABC-like ATPase machinery and find that both ATPase sites contribute to DNA loading, whereas DNA release is controlled specifically by one site. We propose that Smc3 acetylation locks cohesin rings around the sister chromatids by counteracting an activity associated with one of cohesin's two ATPase sites. PMID- 26895430 TI - Erratum to: Advancing drug delivery systems for the treatment of multiple sclerosis. PMID- 26895431 TI - Radiological Risk Assessment by Convergence Methodology Model in RDD Scenarios. AB - A radiological dispersal device (RDD) is a simple weapon capable of causing human harm, environmental contamination, disruption, area denial, and economic cost. It can affect small, large, or long areas depending on atmospheric stability. The risk of developing a radio-induced cancer depends on exposure, and an effective response depends upon available timely guidance. This article proposes and demonstrates a convergence of three different capabilities to assess risk and support rapid safe resource efficient response. The three capabilities that are integrated are Hotspot for dispersion, RERF for epidemiological risk, and RESRAD RDD for response guidance. The combined methodology supports decisions on risk reduction and resource allocation through work schedules, the designation and composition of response teams, and siting for operations. In the illustrative RDD scenario, the contamination area for sheltering, evacuation, and long-term public concern was greatest for calm atmospheric conditions, whilst close-quarter responders faced highest dose rates for neutral atmospheric conditions. Generally, the risks to women responders were found to be significantly greater than for men, and the risks to 20-year-old responders were three times that of their 60-year-old counterparts for similar exposure. PMID- 26895432 TI - Comparative study of periostin expression in different respiratory samples in patients with asthma and chronic obstructive pulmonary disease. AB - INTRODUCTION: Periostin is considered to be a marker of eosinophilic inflammation in patients with asthma. However, there are no literature data on periostin in patients with chronic obstructive pulmonary disease (COPD). OBJECTIVES The aim of the study was to evaluate periostin expression and to compare its concentrations in various materials in patients with mild-to-moderate asthma and COPD, as well as to evaluate the potential association between periostin and clinical features of both diseases. PATIENTS AND METHODS: Using an enzyme-linked immunosorbent assay, we measured periostin concentrations in serum, induced sputum (IS), exhaled breath condensate (EBC), and bronchoalveolar lavage fluid (BALF) as well as periostin expression in bronchial biopsy samples in 24 patients with asthma, 36 patients with COPD, and 12 controls. Correlations between periostin levels in different materials were also analyzed and periostin concentrations were compared between patients with asthma and those with COPD. RESULTS: Periostin levels were detectable in serum, IS, EBC, and BALF from patients with asthma, COPD, and controls. EBC periostin levels correlated with tissue periostin expression and were significantly higher in asthma than in COPD (P = 0.04). Periostin expression in bronchial mucosa was higher in asthma than in COPD (P <0.001), as well as in asthma and COPD patients compared with controls (P <0.001). No significant correlations between tissue periostin expression and BALF, IS, or serum periostin levels were found. There were no differences in serum, IS, BALF, or EBC periostin concentrations between patients with different phenotypes of both diseases. CONCLUSIONS: Periostin may be detected not only in serum, IS, and airway tissue samples, but also in EBC and BALF. EBC periostin levels and tissue periostin expression are higher in patients with asthma than in those with COPD. EBC periostin levels may serve as a potential surrogate marker for tissue periostin expression. PMID- 26895433 TI - In Vitro Effects of the Endocrine Disruptor p,p'-DDT on Human Follitropin Receptor. AB - BACKGROUND: 1-chloro-4-[2,2,2-trichloro-1-(4-chlorophenyl)ethyl]benzene (p,p' DDT) is a persistent environmental endocrine disruptor (ED). Several studies have shown an association between p,p'-DDT exposure and reproductive abnormalities. OBJECTIVES: To investigate the putative effects of p,p'-DDT on the human follitropin receptor (FSHR) function. METHODS AND RESULTS: We used Chinese hamster ovary (CHO) cells stably expressing human FSHR to investigate the impact of p,p'-DDT on FSHR activity and its interaction with the receptor. At a concentration of 5 MUM p,p'-DDT increased the maximum response of the FSHR to follitropin by 32 +/- 7.45%. However, 5 MUM p,p'-DDT decreased the basal activity and did not influence the maximal response of the closely related LH/hCG receptor to human chorionic gonadotropin (hCG). The potentiating effect of p,p'-DDT was specific for the FSHR. Moreover, in cells that did not express FSHR, p,p'-DDT had no effect on cAMP response. Thus, the potentiating effect of p,p'-DDT was dependent on the FSHR. In addition, p,p'-DDT increased the sensitivity of FSHR to hCG and to a low molecular weight agonist of the FSHR, 3-((5methyl)-2-(4 benzyloxy-phenyl)-5-{[2-[3-ethoxy-4-methoxy-phenyl)-ethylcarbamoyl]-methyl}-4-oxo thiazolidin-3-yl)-benzamide (16a). Basal activity in response to p,p'-DDT and potentiation of the FSHR response to FSH by p,p'-DDT varied among FSHR mutants with altered transmembrane domains (TMDs), consistent with an effect of p,p'-DDT via TMD binding. This finding was corroborated by the results of simultaneously docking p,p'-DDT and 16a into the FSHR transmembrane bundle. CONCLUSION: p,p'-DDT acted as a positive allosteric modulator of the FSHR in our experimental model. These findings suggest that G protein-coupled receptors are additional targets of endocrine disruptors. CITATION: Munier M, Grouleff J, Gourdin L, Fauchard M, Chantreau V, Henrion D, Coutant R, Schiott B, Chabbert M, Rodien P. 2016. In vitro effects of the endocrine disruptor p,p'-DDT on human follitropin receptor. Environ Health Perspect 124:991-999; http://dx.doi.org/10.1289/ehp.1510006. PMID- 26895434 TI - Internal Jugular Vein Cross-Sectional Area Enlargement Is Associated with Aging in Healthy Individuals. AB - BACKGROUND: Internal jugular vein (IJV) narrowing has been implicated in central nervous system pathologies, however normal physiological age- and gender-related IJV variance in healthy individuals (HIs) has not been adequately assessed. OBJECTIVES: We assessed the relationship between IJV cross-sectional area (CSA) and aging. MATERIALS AND METHODS: This study involved 193 HIs (63 males and 130 females) who received 2-dimensional magnetic resonance venography at 3T. The minimum CSA of the IJVs at cervical levels C2/C3, C4, C5/C6, and C7/T1 was obtained using a semi-automated contouring-thresholding technique. Subjects were grouped by decade. Pearson and partial correlation (controlled for cardiovascular risk factors, including hypertension, heart disease, smoking and body mass index) and analysis of variance analyses were used, with paired t-tests comparing side differences. RESULTS: Mean right IJV CSA ranges were: in males, 41.6 mm2 (C2/C3) to 82.0 mm2 (C7/T1); in females, 38.0 mm2 (C2/C3) to 62.3 mm2 (C7/T1), while the equivalent left side ranges were: in males, 28.0 mm2 (C2/C3) to 52.2 mm2 (C7/T1); in females, 27.2 mm2 (C2/C3) to 47.8 mm2 (C7/T1). The CSA of the right IJVs was significantly larger (p<0.001) than the left at all cervical levels. Controlling for cardiovascular risk factors, the correlation between age and IJV CSA was more robust in males than in the females for all cervical levels. CONCLUSIONS: In HIs age, gender, hand side and cervical location all affect IJV CSA. These findings suggest that any definition of IJV stenosis needs to account for these factors. PMID- 26895435 TI - [Localized prostate cancer: Radiotherapeutic concepts]. AB - BACKGROUND: Radiation therapy is an established cornerstone in the treatment of prostate cancer. Significant advances in the techniques and therapeutic concepts have been made in recent decades. OBJECTIVES: The objective of this article is to provide an overview of current standards of care and recent technical and conceptional developments. CONCLUSIONS: Three-dimensional conformal radiotherapy has long been the standard of care for percutaneous radiotherapy. The development of intensity-modulated radiation therapy (IMRT) and image-guided radiation therapy (IGRT) have increased the precision of treatment, thus, reducing side effects and allowing dose escalation. LDR (low dose rate) and HDR (high dose rate) brachytherapy alone or in combination are a treatment option in localized prostate cancer with a distinct side effect profile. The roles of proton therapy and stereotactic radiotherapy should be further investigated in prospective trials. PMID- 26895436 TI - Revisiting a Classic Study of the Molecular Clock. AB - A constant rate of molecular evolution among homologous proteins and across lineages is known as the molecular clock. This concept has been useful for estimating divergence times. Here, we revisit a study by Richard Dickerson (J Mol Evol 1:26-45, 1971), wherein he provided striking visual evidence for a constant rate of amino acid changes among various evolutionary branch points. Dickerson's study is commonly cited as support of the molecular clock and a figure from it is often reproduced in textbooks. Since its publication, however, there have been updates made to dates of common ancestors based on the fossil record that should be considered. Additionally, collecting the accession numbers and carefully outlining Dickerson's methods serves as a resource to students of the molecular clock hypothesis. PMID- 26895437 TI - Sustainable heterologous production of terpene hydrocarbons in cyanobacteria. AB - Cyanobacteria can be exploited as photosynthetic platforms for heterologous generation of terpene hydrocarbons with industrial application. However, the slow catalytic activity of terpene synthases (k cat = 4 s-1 or slower) makes them noncompetitive for the pool of available substrate, thereby limiting the rate and yield of product generation. Work in this paper applied transformation technologies in Synechocystis for the heterologous production of beta phellandrene (monoterpene) hydrocarbons. Conditions were defined whereby expression of the beta-phellandrene synthase (PHLS), as a CpcB.PHLS fusion protein with the beta-subunit of phycocyanin, accounted for up to 20 % of total cellular protein. Moreover, CpcB.PHLS was heterologously co-expressed with enzymes of the mevalonic acid (MVA) pathway and geranyl-diphosphate synthase, increasing carbon flux toward the terpenoid biosynthetic pathway and enhancing substrate availability. These improvements enabled yields of 10 mg of beta phellandrene per g of dry cell weight generated in the course of a 48-h incubation period, or the equivalent of 1 % beta-phellandrene:biomass (w:w) carbon-partitioning ratio. The work helped to identify prerequisites for the efficient heterologous production of terpene hydrocarbons in cyanobacteria: (i) requirement for overexpression of the heterologous terpene synthase, so as to compensate for the slow catalytic turnover of the enzyme, and (ii) enhanced endogenous carbon partitioning toward the terpenoid biosynthetic pathway, e.g., upon heterologous co-expression of the MVA pathway, thereby supplementing the native metabolic flux toward the universal isopentenyl-diphosphate and dimethylallyl-diphosphate terpenoid precursors. The two prerequisites are shown to be critical determinants of yield in the photosynthetic CO2 to terpene hydrocarbons conversion process. PMID- 26895438 TI - Oxygen produced by cyanobacteria in simulated Archaean conditions partly oxidizes ferrous iron but mostly escapes-conclusions about early evolution. AB - The Earth has had a permanently oxic atmosphere only since the great oxygenation event (GOE) 2.3-2.4 billion years ago but recent geochemical research has revealed short periods of oxygen in the atmosphere up to a billion years earlier before the permanent oxygenation. If these "whiffs" of oxygen truly occurred, then oxygen-evolving (proto)cyanobacteria must have existed throughout the Archaean aeon. Trapping of oxygen by ferrous iron and other reduced substances present in Archaean oceans has often been suggested to explain why the oxygen content of the atmosphere remained negligible before the GOE although cyanobacteria produced oxygen. We tested this hypothesis by growing cyanobacteria in anaerobic high-CO2 atmosphere in a medium with a high concentration of ferrous iron. Microcystins are known to chelate iron, which prompted us also to test the effects of microcystins and nodularins on iron tolerance. The results show that all tested cyanobacteria, especially nitrogen-fixing species grown in the absence of nitrate, and irrespective of the ability to produce cyanotoxins, were iron sensitive in aerobic conditions but tolerated high concentrations of iron in anaerobicity. This result suggests that current cyanobacteria would have tolerated the high-iron content of Archaean oceans. However, only 1 % of the oxygen produced by the cyanobacterial culture was trapped by iron, suggesting that large-scale cyanobacterial photosynthesis would have oxygenated the atmosphere even if cyanobacteria grew in a reducing ocean. Recent genomic analysis suggesting that ability to colonize seawater is a secondary trait in cyanobacteria may offer a partial explanation for the sustained inefficiency of cyanobacterial photosynthesis during the Archaean aeon, as fresh water has always covered a very small fraction of the Earth's surface. If oxygenic photosynthesis originated in fresh water, then the GOE marks the adaptation of cyanobacteria to seawater, and the late-Proterozoic increase in oxygen concentration of the atmosphere is caused by full oxidation of the oceans. PMID- 26895439 TI - A Proteomic Approach Identifies Candidate Early Biomarkers to Predict Severe Dengue in Children. AB - BACKGROUND: Severe dengue with severe plasma leakage (SD-SPL) is the most frequent of dengue severe form. Plasma biomarkers for early predictive diagnosis of SD-SPL are required in the primary clinics for the prevention of dengue death. METHODOLOGY: Among 63 confirmed dengue pediatric patients recruited, hospital based longitudinal study detected six SD-SPL and ten dengue with warning sign (DWS). To identify the specific proteins increased or decreased in the SD-SPL plasma obtained 6-48 hours before the shock compared with the DWS, the isobaric tags for relative and absolute quantification (iTRAQ) technology was performed using four patients each group. Validation was undertaken in 6 SD-SPL and 10 DWS patients. PRINCIPAL FINDINGS: Nineteen plasma proteins exhibited significantly different relative concentrations (p<0.05), with five over-expressed and fourteen under-expressed in SD-SPL compared with DWS. The individual protein was classified to either blood coagulation, vascular regulation, cellular transport related processes or immune response. The immunoblot quantification showed angiotensinogen and antithrombin III significantly increased in SD-SPL whole plasma of early stage compared with DWS subjects. Even using this small number of samples, antithrombin III predicted SD-SPL before shock occurrence with accuracy. CONCLUSION: Proteins identified here may serve as candidate predictive markers to diagnose SD-SPL for timely clinical management. Since the number of subjects are small, so further studies are needed to confirm all these biomarkers. PMID- 26895442 TI - A Valuable Option in the Management of Female Recurrent Stress Urinary Incontinence: Re-Adjustable Sling (Remeex Sling System). AB - INTRODUCTION: This study was conducted to evaluate the effectiveness and safety of adjustable slings in the treatment of recurrent stress urinary incontinence (SUI) after mid-urethral sling (MUS) failure. MATERIALS AND METHODS: A prospective study was performed among women with recurrent SUI at the Urogynecology Division of Istanbul School of Medicine between February 2010 and March 2015. All women were preoperatively evaluated with detailed urogynecologic evaluations, which included pelvic examination, Q-tip test, pad test, urodynamic studies and a compilation of the Kings Health Questionnaire (KHQ). Postoperative follow-up was performed at 1, 6 and 12 months and annually thereafter. Our primary outcome was objective cure and patient's satisfaction with treatment. Secondary outcomes included perioperative complications and adverse events. RESULTS: Nineteen women were included in the study. The patients' mean age was 55.3 +/- 6.9 years (range 43-66 years). The median follow-up time was 20.7 +/- 14.0 months (range 6-55 months). The overall cure and improvement rates were 84.2 and 10.5%, respectively. In the satisfaction questionnaire, 15 (79%) patients responded that they were very satisfied and 3 (15.7%) were moderately satisfied. Sling tension re-adjustment was needed during follow-up in 1 patient (5.3%), 13 months after the initial surgery. The preoperative mean KHQ score was 545.9 +/- 243.0 and changed to 237.0 +/- 217.5 (p < 0.05). Postoperative complications were slight and easily manageable. CONCLUSIONS: Recurrent SUI is a challenging condition in urogynecology. The Regulation Mechanical External (Remeex) system has been found to be effective in the treatment of recurrent SUI after MUS failure with acceptable adverse effects. The Remeex system has the advantage of re-adjustment as a valuable option in the long-term management of patients. PMID- 26895441 TI - Interleukin-9 Overexpression and Th9 Polarization Characterize the Inflamed Gut, the Synovial Tissue, and the Peripheral Blood of Patients With Psoriatic Arthritis. AB - OBJECTIVE: To investigate the expression and tissue distribution of Th9-related cytokines in patients with psoriatic arthritis (PsA). METHODS: Quantitative gene expression analysis of Th1, Th17, and Th9 cytokines was performed in intestinal biopsy samples obtained from patients with PsA, HLA-B27-positive patients with ankylosing spondylitis (AS), patients with Crohn's disease (CD), and healthy controls. Expression and tissue distribution of interleukin-23 (IL-23), IL-17, IL 22, IL-9, and IL-9 receptor (IL-9R) were evaluated by immunohistochemistry and confocal microscopy. Flow cytometry was used to study the frequency of Th9 cells among peripheral blood, lamina propria, and synovial fluid mononuclear cells. The functional relevance of IL-9R expression on epithelial cells was assessed in functional in vitro studies. Th9 cells in synovial tissue from patients with PsA were also studied. RESULTS: Subclinical gut inflammation in PsA patients was characterized by a clear Th17 and Th22, but not Th1, polarized immune response. Unlike AS and CD, a strong and significant up-regulation of IL-9 was observed in PsA gut, especially among infiltrating mononuclear cells, high endothelial venules, and Paneth cells. IL-9-positive mononuclear cells were demonstrated to be in large part Th9 cells. IL-9 overexpression was accompanied by significant Paneth cell hyperplasia. Paneth cells strongly overexpressed IL-9R, and stimulation of epithelial cells, isolated from PsA patients, with IL-9 resulted in overexpression of alpha-defensin 5 and IL-23p19. Peripheral and synovial expansion of alpha4beta7+ Th9 cells was also observed in patients with PsA. Increased expression of IL-9 and IL-9R was also found in synovial tissue. CONCLUSION: Strong IL-9/Th9 polarization seems to be the predominant immunologic signature in patients in PsA. PMID- 26895443 TI - Technology: Bridging the Gap from Research to Practice. PMID- 26895440 TI - Pathogenic and Genotypic Characterization of a Japanese Encephalitis Virus Isolate Associated with Reproductive Failure in an Indian Pig Herd. AB - BACKGROUND: India is endemic to Japanese encephalitis virus (JEV) and recurrent outbreaks occur mainly in rice growing areas. Pigs are considered to be the amplifying host for JEV and infection in gestating pigs results in reproductive failure. Most studies conducted on JEV infection in Indian pigs have been serological surveys and very little is known about JEV genotypes circulating in pigs. So the potential risk posed by pigs in JEV transmission and the genetic relationship between viruses circulating in pigs, mosquitoes and humans is poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: This study was conducted in pigs with a history of reproductive failure characterized by stillborn piglets with neuropathological lesions. Japanese encephalitis (JE) suspected brain specimens inoculated intracerebrally into mice and Vero cells resulted in successful isolation of JEV/SW/IVRI/395A/2014. Clinicopathological observations in infected mice, demonstration of JEV antigen in brain, and analysis of the envelope protein identified the swine isolate as being neurovirulent. Phylogenetic analysis based on prM and E gene sequences showed that it belonged to genotype III. This swine isolate was closely related to JEV associated with the 2005 outbreak in India and JaoArS982 from Japan. Phylogenetic analysis of JEV strains collected between 1956 and 2014 in India categorized the GIII viruses into different clades blurring their spatial distribution, which has been discernible in the previous century. CONCLUSIONS/SIGNIFICANCE: Isolation of JEV from stillborn piglets and its close genetic relationship with viruses detected at least three decades ago in humans and mosquitoes in Japan suggests that the virus may have been circulating among Indian pigs for several decades. The close similarity between the present swine isolate and those detected in humans affected in the 2005 outbreak in Uttar Pradesh, India, suggests the need for more intensive surveillance of pigs and implementation of suitable strategies to control JE in India. PMID- 26895444 TI - The Relationship between Traumatic Life Events and Hoarding Symptoms: A Multi Method Approach. AB - Hoarding Disorder is characterized by difficulties with discarding and frequently excessively acquiring possessions, resulting in substantial clutter. Previous research has implicated trauma in the development of hoarding, but no study to date has examined the relationship between trauma and hoarding using hypothetical hoarding paradigms. This study investigated the association between traumatic events and both self-report and hypothetical indices of hoarding symptoms. We predicted that frequency of trauma would be associated with greater hoarding symptoms (across self-report and hypothetical indices). Undergraduate students (N = 80) completed self-report measures of hoarding symptoms and trauma, and hypothetical measures of acquiring and saving tendencies. As expected, more frequent trauma, and physical/sexual trauma in particular, was associated with greater acquiring tendencies. However, frequency of trauma was not significantly correlated with saving tendencies or self-reported hoarding symptoms. Future research should replicate these findings using longitudinal designs to confirm whether trauma actually serves as a risk factor for hoarding. Replication in a clinical sample is needed to better understand the implications of these results for intervention. PMID- 26895445 TI - Clinical pharmacokinetics and pharmacodynamics of ramucirumab in the treatment of colorectal cancer. AB - INTRODUCTION: Colorectal cancer is the third most common cancer worldwide. The prognosis of colorectal cancer patients still remains dismal and half of them will develop metastatic disease. Angiogenesis plays an essential role in colorectal tumorigenesis, and the VEGF pathway is one of the targets that has been validated up to now. The use of antiangiogenics along with chemotherapy has become an accepted standard for colorectal cancer. AREAS COVERED: This review discusses the efficacy and safety profile of ramucirumab, a fully human immunoglobulin G1 monoclonal antibody against the vascular endothelial growth factor receptor-2 (VEGFR-2), for the treatment of second-line metastatic colorectal cancer upon progression to first-line chemotherapy including anti angiogenics. EXPERT OPINION: Ramucirumab in combination with chemotherapy represents a valid option in second-line treatment of advanced colorectal cancer patients, who progressed on previous bevacizumab-based combinations. This agent demonstrates a similar benefit in terms of overall survival to other angiogenesis inhibitors (bevacizumab and ziv-aflibercept) used in this setting. PMID- 26895446 TI - Medio-lateral knee fluency in anterior cruciate ligament-injured athletes during dynamic movement trials. AB - BACKGROUND: Correction of neuromuscular impairments after anterior cruciate ligament injury is vital to successful return to sport. Frontal plane knee control during landing is a common measure of lower-extremity neuromuscular control and asymmetries in neuromuscular control of the knee can predispose injured athletes to additional injury and associated morbidities. Therefore, this study investigated the effects of anterior cruciate ligament injury on knee biomechanics during landing. METHODS: Two-dimensional frontal plane video of single leg drop, cross over drop, and drop vertical jump dynamic movement trials was analyzed for twenty injured and reconstructed athletes. The position of the knee joint center was tracked in ImageJ software for 500 milliseconds after landing to calculate medio-lateral knee motion velocities and determine normal fluency, the number of times per second knee velocity changed direction. The inverse of this calculation, analytical fluency, was used to associate larger numerical values with fluent movement. FINDINGS: Analytical fluency was decreased in involved limbs for single leg drop trials (P=0.0018). Importantly, analytical fluency for single leg drop differed compared to cross over drop trials for involved (P<0.001), but not uninvolved limbs (P=0.5029). For involved limbs, analytical fluency values exhibited a stepwise trend in relative magnitudes. INTERPRETATION: Decreased analytical fluency in involved limbs is consistent with previous studies. Fluency asymmetries observed during single leg drop tasks may be indicative of abhorrent landing strategies in the involved limb. Analytical fluency differences in unilateral tasks for injured limbs may represent neuromuscular impairment as a result of injury. PMID- 26895447 TI - Differences in anatomical parameters between the affected and unaffected hip in patients with bilateral cam-type deformities. AB - BACKGROUND: It is still unclear why many individuals with bilateral cam deformities demonstrate only unilateral symptoms of femoroacetabular impingement, thus symptoms may be attributed to additional anatomical parameters. The purpose was to examine patients with bilateral cam deformities, with unilateral symptoms, and compare anatomical hip joint parameters between their affected (symptomatic) hip and their contralateral, unaffected (asymptomatic) hip. METHODS: Twenty participants (n=20) with unilateral symptoms, but bilateral cam deformities, underwent CT imaging to measure their affected and unaffected hip's: axial and radial alpha angles, femoral head-neck offset, femoral neck-shaft angle, medial proximal femoral angle, femoral torsion, acetabular version, center-edge angle; and a physical examination (hip flexion, straight-leg raise, internal rotation, external rotation) to ascertain clinical signs. FINDINGS: The affected hips demonstrated limited motions during physical examination, compared with unaffected hips (effect size=0.550 to 0.955). The affected hips had significantly lower femoral neck-shaft angles (mean 125 degrees (SD 3)) and lower medial proximal femoral angles (mean 79 degrees (SD 4)), compared with the unaffected hips (mean 127 degrees (SD 3), P=0.001, effect size=0.922; and mean 81 degrees (SD 4), P=0.011, effect size=0.632; respectively). There were no differences in cam deformity parameters (axial and radial alpha angles, femoral head-neck offset), femoral torsion, acetabular version, and center-edge angle, between affected and unaffected hips. INTERPRETATION: A decreased femoral neck-shaft angle or medial proximal femoral angle can be implemented as a diagnostic predictor, to determine which hip may be at a greater risk of developing early symptoms. PMID- 26895449 TI - Annual report 2015. PMID- 26895450 TI - Formulation factors affecting the isomerization rate of betamethasone-17-valerate in a developmental hydrophilic cream - a HPLC and microscopy based stability study. AB - The formulation of betamethasone-17-valerate (BV) into topical medicines presents a significant challenge for the formulation chemist. The substance is susceptible to acid and base catalyzed isomerization in aqueous environments, which results in valerate transesterification from carbon 17 to carbon 21 of the steroid ring system. This acyl migration process is of significant clinical importance since the 21-valerate ester possesses only a fraction of the potency of the 17-valerate parent compound. Isomerization of BV should therefore be reduced to a minimum through design of a suitable drug vehicle. In this study, the effect of varying the concentration of several excipient components on the isomerization rate of betamethasone valerate in a model hydrophilic cream has been investigated. These excipients include the emulsifier macrogolstearylether-20/21, the co-emulsifier cetylstearyl alcohol and the thickening agent hydroxyl propyl methylcellulose. Additionally, the influence of pH, the presence of the antioxidant, alpha tocopherol, as well as the chelating agent, disodium edetate, on the stability of the formulation have been investigated. Trial drug product formulations, which were designed to investigate the influence of the above-mentioned components/parameters were manufactured and their stability was tested according to current ICH Guidelines. The content, purity and crystalline structure of the active substance in these formulations was analyzed by a combination of HPLC and microscopy techniques. The study demonstrates that the rate of isomerization of betamethasone valerate depends significantly on the concentration of emulsifier used in the cream formulation. At higher concentrations of emulsifier the isomerization proceeds rapidly with significant degradation over a period of weeks, whereas at lower concentrations significant degradation may not be observed, even after several years' storage. The influence of the emulsifier has been shown to be independent of the pH value of the aqueous phase of the cream. These findings have not been reported in previous literature reports on this topic, which have tended to focus on the influence of pH. The results are likely to be of interest to pharmaceutical chemists working on the formulation of glucocorticoids as well as to local- and hospital pharmacists who carry out the practice of dilution of proprietary corticoid preparations, where the choice of diluent is likely to be critical for ensuring the stability of the diluted product. PMID- 26895451 TI - Recurrent Selection for Transgene Activity Levels in Maize Results in Proxy Selection for a Native Gene with the Same Promoter. AB - High activity levels of a transgene can be very useful, making a transgene easier to evaluate for safety and efficacy. High activity levels can also increase the economic benefit of the production of high value proteins in transgenic plants. The goal of this research is to determine if recurrent selection for activity of a transgene will result in higher activity, and if selection for activity of a transgene controlled by a native promoter will also increase protein levels of the native gene with the same promoter. To accomplish this goal we used transgenic maize containing a construct encoding green fluorescent protein controlled by the promoter for the maize endosperm-specific 27 kDa gamma zein seed storage protein. We carried out recurrent selection for fluorescence intensity in two breeding populations. After three generations of selection, both selected populations were significantly more fluorescent and had significantly higher levels of 27 kDa gamma zein than the unselected control populations. These higher levels of the 27 kDa gamma zein occurred independently of the presence of the transgene. The results show that recurrent selection can be used to increase activity of a transgene and that selection for a transgene controlled by a native promoter can increase protein levels of the native gene with the same promoter via proxy selection. Moreover, the increase in native gene protein level is maintained in the absence of the transgene, demonstrating that proxy selection can be used to produce non-transgenic plants with desired changes in gene expression. PMID- 26895452 TI - Disrupting monotony while increasing demand: benefits of rest and intervening tasks on vigilance. AB - In the experiments presented here, we examined the impact of intervening tasks on the vigilance decrement. In Experiment 1 participants either (a) continuously performed a visuospatial vigilance task, (b) received a rest break, or (c) temporarily performed a different, demanding visuospatial task in the middle of the vigil. Both taking a rest break and performing the intervening task were found to alleviate the vigilance decrement in response times. Target detection accuracy was equivalent across groups. In Experiment 2 we obtained subjective ratings of task demand, boredom, motivation, and mind wandering for both the vigilance task and intervening task administered in Experiment 1. The intervening task was rated as more demanding in terms of mental demand, physical demand, temporal demand, own performance, effort, and frustration. In addition, participants also reported being more bored, less motivated, and reported mind wandering more frequently when completing the vigil. Disruptions to task monotony (even if cognitively demanding), can alleviate the vigilance decrement. The implications of this finding with respect to current theoretical accounts of the vigilance decrement are discussed. PMID- 26895453 TI - Serum Albumin Concentrations Predict hypovolaemia Caused by Polyethylene Glycol Plus Ascorbic Acid Prior to Colonoscopy in Elderly Patients. AB - BACKGROUND: Previous studies have confirmed the safety of polyethylene glycol plus ascorbic acid for healthy middle-aged adults but not for the elderly. The osmotic pressure of polyethylene glycol plus ascorbic acid is approximately twice that of plasma osmolality and may cause dehydration. OBJECTIVE: In this study, we determined whether dehydration was induced in elderly patients by polyethylene glycol plus ascorbic acid, and we analysed the data obtained in order to identify predictors of dehydration. METHODS: This was a prospective, uncontrolled, before and-after intervention study. All patients older than 65 years who underwent colonoscopies at the Moji Medical Center were administered polyethylene glycol plus ascorbic acid prior to colonoscopy. Clinical variables before and after bowel preparation were measured and analysed statistically. A multiple linear regression analysis was performed to identify predictors of dehydration due to this procedure. RESULTS: Eighty-three patients were assessed for eligibility, and 74 clinical variables were ultimately analysed. A significant increase in the red blood cell count (4.10 versus 4.25 * 10(6)/mm(3)), haemoglobin level (12.4 versus 13.0 g/dL) and haematocrit (38.1% versus 39.4%) suggested the presence of hypovolaemia after the procedure (P < 0.001). The serum concentration of albumin before bowel preparation was identified as the only significant predictor of hypovolaemia (beta = 0.47, P = 0.0001, adjusted R (2) = 0.22). CONCLUSION: The serum concentration of albumin before bowel preparation predicted hypovolaemia caused by polyethylene glycol plus ascorbic acid in elderly patients. Therefore, care is needed in order to prevent hypovolaemia, especially in elderly patients with hypoalbuminaemia. TRIAL REGISTRATION: No. 000015724 (University Hospital Medical Information Network Center). PMID- 26895454 TI - Evolution of Clinical Pharmacy in the USA and Future Directions for Patient Care. AB - This paper describes key events in pharmaceutical education, training, practice, and research that have occurred over the past 55 years. Some of these events included the development of the doctor of pharmacy degree, residency training, and co-location of clinical pharmacists in patient care areas. These changes not only necessitated more specialized training but then led to board certification to ensure quality patient care. Specific examples of the research that have supported the involvement of clinical pharmacists in direct patient care will be discussed. PMID- 26895456 TI - Relationship between hepatic progenitor cell-mediated liver regeneration and non parenchymal cells. AB - Hepatic progenitor cells (HPCs) are thought to reside in the canals of Hering and can be activated and contribute to liver regeneration in response to liver injury by proliferating and differentiating towards both hepatocytes and biliary epithelial cells. In this setting, several cytokines, chemokines, and growth factors related to liver inflammation and other liver cells comprising the HPC niche, namely hepatic stellate cells (HSCs), play crucial roles in HPC activation and differentiation. In response to several types of liver injury, tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is secreted by several inflammatory cells, including monocytes, T lymphocytes, and macrophages, and acts as an initiator of the HPC niche and HSC activation. Following TWEAK-induced activation of the HPC niche, fibroblast growth factor 7 and hepatocyte growth factor released from activated HSC play central roles in maintaining HPC proliferation. In contrast, HGF-MET and Wnt3a-beta-catenin signals are the predominant mediators of the hepatocyte differentiation of HPC, whereas epidermal growth factor receptor-NOTCH signaling controls HPC differentiation towards biliary epithelial cells. These signals are maintained exclusively by activated HSC and inflammatory cells surrounding HPC. Together, HSC and inflammatory cells surrounding HPC are responsible for the precise control of HPC proliferation and differentiation fate. In this review, we discuss recent progress in understanding of interactions between HPC and other liver cells in HPC-mediated liver regeneration in the setting of liver inflammation. PMID- 26895457 TI - Hypermethylated Chromosome Regions in Nine Fish Species with Heteromorphic Sex Chromosomes. AB - Sites and amounts of 5-methylcytosine (5-MeC)-rich chromosome regions were detected in the karyotypes of 9 Brazilian species of Characiformes fishes by indirect immunofluorescence using a monoclonal anti-5-MeC antibody. These species, belonging to the genera Leporinus, Triportheus and Hoplias, are characterized by highly differentiated and heteromorphic ZW and XY sex chromosomes. In all species, the hypermethylated regions are confined to constitutive heterochromatin. The number and chromosome locations of hypermethylated heterochromatic regions in the karyotypes are constant and species-specific. Generally, heterochromatic regions that are darkly stained by the C-banding technique are distinctly hypermethylated, but several of the brightly fluorescing hypermethylated regions merely exhibit moderate or faint C banding. The ZW and XY sex chromosomes of all 9 analyzed species also show species-specific heterochromatin hypermethylation patterns. The analysis of 5-MeC rich chromosome regions contributes valuable data for comparative cytogenetics of closely related species and highlights the dynamic process of differentiation operating in the repetitive DNA fraction of sex chromosomes. PMID- 26895455 TI - Pseudodrusen in the Fellow Eye of Patients with Unilateral Neovascular Age Related Macular Degeneration: A Meta-Analysis. AB - IMPORTANCE: The fellow eye of patients with unilateral neovascular age-related degeneration (nAMD) is at increased risk of developing late AMD. Several cohort studies have evaluated the prevalence of pseudodrusen and the association between pseudodrusen and late AMD in the fellow eye of patients with unilateral nAMD. However, these studies have limited sample sizes and their results are inconsistent. OBJECTIVE: To evaluate the prevalence rate of pseudodrusen, and the association between pseudodrusen and incidence of late AMD (nAMD and geographic atrophy (GA)) in the fellow eye of patients with unilateral nAMD. DATA SOURCES: The PubMed, EMBASE, Web of Science, and Cochrane Library databases were searched up to July 2015, as well as other systematic reviews. STUDY SELECTION: All cohort studies for pseudodrusen with late AMD in the fellow eye of patients with unilateral nAMD. DATA EXTRACTION AND SYNTHESIS: The numbers of patients with and without pseudodrusen at baseline and the numbers of incident nAMD and GA during follow up among patients with and without pseudodrusen were independently extracted by 2 authors. The results were pooled using random-effects meta analysis. Heterogeneity was assessed using the I2 test. MAIN OUTCOME MEASURES: Prevalence rate of pseudodrusen, risk ratios (RRs) and their 95% confidence intervals (95% CIs) for associations between pseudodrusen and the incidence of nAMD and GA in the fellow eye. RESULTS: Five cohort studies (N = 677 patients) from 8 countries across 4 continents were included. The pooled prevalence rate of pseudodrusen in the fellow eye was 48.1% (95% Cl: 36.7-59.5%, I2 = 87%). Pseudodrusen were associated with an increased risk of nAMD (RR = 1.54, 95% Cl: 1.10-2.16, I2 = 42%), GA (RR = 4.70, 95% Cl: 1.22-18.1, I2 = 64%), and late AMD (RR = 2.03, 95% Cl: 1.35-3.06, I2 = 60%). CONCLUSIONS: For patients with unilateral nAMD, pseudodrusen were present in about half of the fellow eyes. The presence of pseudodrusen was associated with a 1.5 times higher risk of developing nAMD, a 4.7 times higher risk of developing GA, and a 2 times higher risk of developing late AMD. Pseudodrusen should be considered in evaluating the risk of late AMD development; however, due to considerable heterogeneity across these studies, a larger study is needed to validate these findings. PMID- 26895458 TI - Dithranol treatment of plaque-type psoriasis increases serum TNF-like weak inducer of apoptosis (TWEAK). AB - PURPOSE: TNF-like weak inducer of apoptosis (TWEAK) mediates not only apoptosis, but also inflammation, cell growth and angiogenesis. The role of TWEAK in psoriasis remains unknown. The aim of the study was to assess serum levels of TWEAK in psoriatic patients before and after topical treatment with dithranol in relation to the clinical activity of the disease. MATERIAL AND METHODS: Serum samples were collected from 40 patients with plaque type psoriasis before and after topical treatment with dithranol. The concentrations of serum TWEAK were measured by ELISA and next compared with 16 healthy controls. The data were analyzed with respect to Psoriasis Area and Severity Index (PASI). RESULTS: Baseline serum TWEAK concentrations of psoriatic patients (685+/-166pg/ml) were significantly greater compared to healthy controls (565+/-110pg/ml). Topical treatment resulted in further increase in serum TWEAK (749+/-179pg/ml; p<0.01). In case of patients with initial serum TWEAK concentrations above the median, PASI after topical treatment was lower compared to the individuals with initial TWEAK below the median. CONCLUSION: According to the study, serum Tweak was increased in psoriasis patients compared with controls. Moreover, dithranol topical treatment caused further increase in serum TWEAK. Also, a higher effectiveness of topical treatment was observed in case of patients with higher initial TWEAK concentrations. The results suggest a potential role of TWEAK in psoriasis therapy. PMID- 26895459 TI - PET/CT and MRI directed extended salvage radiotherapy in recurrent prostate cancer with lymph node metastases. AB - PURPOSE: PET/CT directed extended salvage radiotherapy (esRT) of involved lymph node (LN) regions may be a salvage strategy for patients with nodal recurrent prostate cancer (PCa) after primary therapy or after previous prostate fossa salvage RT. The aim of the study was to determine the time until prostate specific antigen (PSA) progression, pattern of failure and toxicity after esRT. MATERIAL AND METHODS: 25 patients with nodal or nodal+local recurrent PCa confirmed by Choline-PET/CT and Magnetic Resonance Imaging (MRI) were treated with esRT at the sites of recurrence. Acute and late toxicity was recorded. In case of subsequent PSA progression, imaging was performed to confirm next relapse. Mean follow-up was 2.9 years. RESULTS: According to Choline-PET/CT and MRI findings, 84% (21/25) of esRT were treatment of pelvic only, 12% (3/25) of retroperitoneal only and 4% (1/25) of both pelvic and retroperitoneal regions. 40% (10/25) received concomitant irradiation of the prostatic fossa (after primary radical prostatectomy). Median time to PSA progression of the whole cohort was 19.6 months. Median time to PSA progression for patients with 1-2 PET positive LN (n=15) was 34.9 months versus median 12.7 months for patients with PET-positive LN>=3 (n=10), p-value: 0.0476. Acute and late toxicity was mild to moderate, no grade-3 adverse events were observed. CONCLUSION: PET/CT and MRI directed esRT of nodal recurrent PCa with or without local recurrence is feasible with low acute and late toxicity. Patients with only one or two PET-positive LN treated by esRT achieved prolonged complete biochemical remission. PMID- 26895460 TI - NNP-Type Pincer Imidazolylphosphine Ruthenium Complexes: Efficient Base-Free Hydrogenation of Aromatic and Aliphatic Nitriles under Mild Conditions. AB - A series of seven novel N(Im)N(H)P-type pincer imidazolylphosphine ruthenium complexes has been synthesized and fully characterized. The use of hydrogenation of benzonitrile as a benchmark test identified [RuHCl(CO)(N(Im)N(H) P(tBu))] as the most active catalyst. With its stable Ru-BH4 analogue, in which chloride is replaced by BH4, a broad range of (hetero)aromatic and aliphatic nitriles, including industrially interesting adiponitrile, has been hydrogenated under mild and base-free conditions. PMID- 26895461 TI - EDGA: A Population Evolution Direction-Guided Genetic Algorithm for Protein Ligand Docking. AB - Protein-ligand docking can be formulated as a search algorithm associated with an accurate scoring function. However, most current search algorithms cannot show good performance in docking problems, especially for highly flexible docking. To overcome this drawback, this article presents a novel and robust optimization algorithm (EDGA) based on the Lamarckian genetic algorithm (LGA) for solving flexible protein-ligand docking problems. This method applies a population evolution direction-guided model of genetics, in which search direction evolves to the optimum solution. The method is more efficient to find the lowest energy of protein-ligand docking. We consider four search methods-a tradition genetic algorithm, LGA, SODOCK, and EDGA-and compare their performance in docking of six protein-ligand docking problems. The results show that EDGA is the most stable, reliable, and successful. PMID- 26895464 TI - Fluorescent Aromatic Tag-Functionalized MOFs for Highly Selective Sensing of Metal Ions and Small Organic Molecules. AB - By varying the fluorescent tags of resorcin[4]arene-based tetracarboxylic acids from phenyl to naphthyl, two highly luminescent metal-organic frameworks (MOFs), namely, [Zn2(TPC4A)(DMF)(H2O)4].3H2O (1) and [(CH3)2NH2]2[Zn(TNC4A)].4H2O (2), were successfully achieved (TPC4A = 2,8,14,20-tetra-phenyl-6,12,18,24-tetra methoxy-4,10,16,22-tetra-carboxy-methoxy-resorcin[4]arene and TNC4A = 2,8,14,20 tetra-1-naphthal-6,12,18,24-tetra- methoxy-4,10,16,22-tetra-carboxy-methoxy resorcin[4]arene). Compound 1 features a unique 2D network, while 2 exhibits a fascinating 3D framework. The highly selective detection of small organic molecules as well as Fe(2+) and Fe(3+) was performed for 1 and 2 as fluorescent sensors. Remarkably, luminescent 1 and 2 were used as sensory materials for the sensing of various amine vapors with high selectivity and rapid response. Most strikingly, clear fluorescence "on-off" switch-functions toward small organic molecules as well as amine vapors were also explored for luminescent 1 and 2. PMID- 26895465 TI - Hypertension on admission is associated with a lower risk of early seizures after stroke. AB - PURPOSE: Despite the common occurrence of early seizures (ES) after stroke, the relationship between risk factors and this complication of stroke is not well established. In this study we have examined the relationship between clinical measures on admission and ES after stroke. METHODS: We included 1073 patients (mean age 69 +/- 12, 51.6% females) with ischemic and haemorrhagic stroke. The frequency of seizure occurrence within 2 weeks of stroke was determined. We used a logistic regression model to analyse the effect of blood pressure on admission and other clinical factors (age, gender, diabetes, atrial fibrillation and dyslipidemia) on the occurrence of ES after stroke. RESULTS: ES occurred after 4.1% and 4.0% of ischemic and haemorrhagic strokes respectively. Compared to patients with high blood pressure on admission, those with low and normal blood pressure had a higher risk of ES after stroke (2.9% vs.7.5% vs. 7.6%, p=0.001). Also the mean age of patients with post-stroke ES was lower (62.5 vs. 69.3, p<0.001). In a logistic regression analysis, low/normal blood pressure remained independently associated with ES after stroke with OR of 2.46 (95% CI 1.38-4.63, p=0.006). CONCLUSION: ES after stroke was equally frequent in patients with ischemic and haemorrhagic stroke. Low/normal blood pressure on admission and younger patient age were risk factors for ES after stroke. PMID- 26895466 TI - Anaerobic co-digestion of agro-food waste mixtures in a fed-batch basis. AB - The agro-food industry (including livestock) generates millions of tonnes of waste products. A solution to this sector's waste disposal challenges was explored by a joint treatment model of organic waste products from several industries. An inventory of agro-food industry organic waste streams with high potential for biogas production was carried out in a logistically viable area (Cider Region, Asturias, Spain). Three industries were selected as those with the higher potential for this study: livestock, dairy and beverage. The kinetics of anaerobic degradation and methane production of four mixtures of selected waste streams were investigated. The specific methane production at five different substrate-to-inoculum ratios (0.50, 0.75, 1.00, 1.50 and 2.00) showed a slightly decreasing trend at the higher ratios. Some hints of a synergistic effect have been observed in mixtures with higher content in milled apple waste, while antagonistic symptoms were noted in mixtures mainly composed of dairy wastes. The estimation of fluxes of waste and methane potentials in the Cider Region suggests centralised anaerobic digestion as a sustainable solution for the valorisation of livestock and agro-food wastes generated in this area. Sector-specific waste streams (livestock and agro-food industry) could cover up to 12% of regional total energy demand. PMID- 26895467 TI - A comprehensive model for quantum noise characterization in digital mammography. AB - A version of cascaded systems analysis was developed specifically with the aim of studying quantum noise propagation in x-ray detectors. Signal and quantum noise propagation was then modelled in four types of x-ray detectors used for digital mammography: four flat panel systems, one computed radiography and one slot-scan silicon wafer based photon counting device. As required inputs to the model, the two dimensional (2D) modulation transfer function (MTF), noise power spectra (NPS) and detective quantum efficiency (DQE) were measured for six mammography systems that utilized these different detectors. A new method to reconstruct anisotropic 2D presampling MTF matrices from 1D radial MTFs measured along different angular directions across the detector is described; an image of a sharp, circular disc was used for this purpose. The effective pixel fill factor for the FP systems was determined from the axial 1D presampling MTFs measured with a square sharp edge along the two orthogonal directions of the pixel lattice. Expectation MTFs were then calculated by averaging the radial MTFs over all possible phases and the 2D EMTF formed with the same reconstruction technique used for the 2D presampling MTF. The quantum NPS was then established by noise decomposition from homogenous images acquired as a function of detector air kerma. This was further decomposed into the correlated and uncorrelated quantum components by fitting the radially averaged quantum NPS with the radially averaged EMTF(2). This whole procedure allowed a detailed analysis of the influence of aliasing, signal and noise decorrelation, x-ray capture efficiency and global secondary gain on NPS and detector DQE. The influence of noise statistics, pixel fill factor and additional electronic and fixed pattern noises on the DQE was also studied. The 2D cascaded model and decompositions performed on the acquired images also enlightened the observed quantum NPS and DQE anisotropy. PMID- 26895462 TI - Therapeutic time window for angiotensin-(1-7) in acute lung injury. AB - BACKGROUND AND PURPOSE: There is presently no proven pharmacological therapy for the acute respiratory distress syndrome. Recently, we and others discovered that the heptapeptide angiotensin-(1-7) [Ang-(1-7)] shows significant beneficial effects in preclinical models of acute lung injury (ALI). Here, we aimed to identify the best time window for Ang-(1-7) administration to protect rats from oleic acid (OA) induced ALI. EXPERIMENTAL APPROACH: The effects of i.v. infused Ang-(1-7) were examined over four different time windows before or after induction of ALI in male Sprague-Dawley rats. Haemodynamic effects were continuously monitored, and loss of barrier function, inflammation and lung peptidase activities were measured as experimental endpoints. KEY RESULTS: Ang-(1 7) infusion provided the best protection against experimental ALI when administered by continuous infusion starting immediately after 30 min OA infusion till the end of the experiment (30-240 min). Both pretreatment (-60 to 0 min before OA) and short-term therapy (30-90 min) also had beneficial effects although less pronounced than the effects achieved with the optimal therapy window. Starting infusion of Ang-(1-7) 60 min after the end of OA treatment (90 240 min) did not protect barrier function or haemodynamics but still reduced myeloperoxidase activity and increased ACE2/ACE activity ratio respectively. CONCLUSIONS AND IMPLICATIONS: Our findings indicate that early initiation of therapy after ALI and continuous drug delivery are most beneficial for optimal therapeutic efficiency of Ang-(1-7) treatment in experimental ALI and, presumably accordingly, in clinical acute respiratory distress syndrome. PMID- 26895468 TI - Does an NKT-cell-based immunotherapeutic approach have a future in multiple myeloma? AB - Natural killer T (NKT) cells constitute a unique subset of innate-like T lymphocytes which differ from conventional T cells by recognizing lipid antigens presented by the non-polymorphic major histocompatibility complex (MHC) I-like molecule CD1d. Despite being a relatively infrequent population of lymphocytes, NKT cells can respond rapidly upon activation with glycosphingolipids by production of cytokines which aim to polarize different axes of the immune system. Due to their dual effector capacities, NKT cells can play a vital role in cancer immunity, infection, inflammation and autoimmune diseases. It is believed that modulation of their activity towards immune activation can be a useful tool in anti-tumor immunotherapeutic strategies. Here we summarize the characteristics of NKT cells and discuss their involvement in immunosurveillance. Furthermore, an update is given about their role and the progress that has been made in the field of multiple myeloma (MM). Finally, some challenges are discussed that are currently hampering further progress. PMID- 26895469 TI - A positive feedback loop involving EGFR/Akt/mTORC1 and IKK/NF-kB regulates head and neck squamous cell carcinoma proliferation. AB - The overexpression or mutation of epidermal growth factor receptor (EGFR) has been associated with a number of cancers, including head and neck squamous cell carcinoma (HNSCC). Increasing evidence indicates that both the phosphatidylinositol-3-kinase (PI3K)-Akt-mammalian target of Rapamycin (mTOR) and the nuclear factor-kappa B (NF-kappaB) are constitutively active and contribute to aggressive HNSCC downstream of EGFR. However, whether these two oncogenic signaling pathways exhibit molecular and functional crosstalk in HNSCC is unclear. Our results now reveal that mTORC1, not mTORC2, contributes to NF-kappaB activation downstream of EGFR/PI3K/Akt signaling. Mechanistically, mTORC1 enhances the inhibitor of nuclear factor kappa-B kinase (IKK) activity to accelerate NF-kappaB signaling. Concomitantly, activated NF-kappaB/IKK up regulates EGFR expression through positive feedback regulation. Blockage of NF kappaB/IKK activity by the novel IKKbeta specific inhibitor, CmpdA, leads to significant inhibition of cell proliferation and induction of apoptosis. CmpdA also sensitizes intrinsic cisplatin-resistant HNSCC cells to cisplatin treatment. Our findings reveal a new mechanism by which EGFR/PI3K/Akt/mTOR signaling promotes head and neck cancer progression and underscores the need for developing a therapeutic strategy for targeting IKK/NF-kappaB either as a single agent or in combination with cisplatin in head and neck cancer. PMID- 26895470 TI - Distinct lncRNA transcriptional fingerprints characterize progressive stages of multiple myeloma. AB - Although many efforts have recently contributed to improve our knowledge of molecular pathogenesis of multiple myeloma (MM), the role and significance of long non-coding RNAs (lncRNAs) in plasma cells (PC) malignancies remains virtually absent. To this aim, we developed a custom annotation pipeline of microarray data investigating lncRNA expression in PCs from 20 monoclonal gammopathies of undetermined significance, 33 smoldering MM, 170 MM, and 36 extra medullary MMs/plasma cell leukemia patients, and 9 healthy donors. Our study identified 31 lncRNAs deregulated in tumor samples compared to normal controls; among these, the upregulation of MALAT1 appeared associated in MM patients with molecular pathways involving cell cycle regulation, p53-mediated DNA damage response, and mRNA maturation processes. Furthermore, we found 21 lncRNAs whose expression were progressively deregulated trough the more aggressive stages of PC dyscrasia, suggesting a possible role in the progression of the disease. Finally, in the context of molecular heterogeneity of MM, we identified a transcriptional fingerprint in hyperdiploid patients, characterized by the upregulation of lncRNAs/pseudogenes related to ribosomal protein genes, known to be upregulated in this molecular group. Overall, the data provides an important resource for future studies on the functions of lncRNAs in the pathology. PMID- 26895471 TI - A novel miR-34a target, protein kinase D1, stimulates cancer stemness and drug resistance through GSK3/beta-catenin signaling in breast cancer. AB - One of the properties of human breast cancer cells is cancer stemness, which is characterized by self-renewal capability and drug resistance. Protein kinase D1 (PRKD1) functions as a key regulator of many cellular processes and is downregulated in invasive breast cancer cells. In this study, we found that PRKD1 was upregulated in MCF-7-ADR human breast cancer cells characterized by drug resistance. Additionally, we discovered that PRKD1 expression was negatively regulated by miR-34a binding to the PRKD1 3'-UTR. PRKD1 expression increased following performance of a tumorsphere formation assay in MCF-7-ADR cells. We also found that reduction of PRKD1 by ectopic miR-34a expression or PRKD1 siRNA treatment resulted in suppressed self-renewal ability in breast cancer stem cells. Furthermore, we confirmed that the PRKD1 inhibitor CRT0066101 reduced phosphorylated PKD/PKCMU, leading to suppression of breast cancer stemness through GSK3/beta-catenin signaling. PRKD1 inhibition also influenced apoptosis initiation in MCF-7-ADR cells. Tumors from nude mice treated with miR-34a or CRT0066101 showed suppressed tumor growth, proliferation, and induced apoptosis. These results provide evidence that regulation of PRKD1, a novel miR-34a target, contributes to overcoming cancer stemness and drug resistance in human breast cancer. PMID- 26895472 TI - mTOR inhibitors, a new era for metastatic luminal HER2-negative breast cancer? A systematic review and a meta-analysis of randomized trials. AB - We evaluated if standard hormonal therapy (HT) could be improved by the addition of mammalian target of rapamycin inhibitors (mTOR-I) in metastatic luminal breast cancer. A meta-analysis on 4 phase II-III randomized clinical trials was performed. Pooled hazard ratio (HR) for progression free survival (PFS)/ time to progression (TTP) was 0.62 in favor of mTOR-I+HT arm (95% confidence interval [CI] 0.55-0.70; p<0.0001). There was significant heterogeneity for PFS/TTP (Cochran's Q 32, p<0.0001, I2 index 90.6%). Pooled HR for overall survival (OS) was 0.84 in favor of the combination arm (95% CI 0.71-0.99; p=0.04). Heterogeneity was not significant (Cochran's Q 4.47, p=0.1, I2 index 55.3%). Pooled risk ratio (RR) for objective response rate (ORR) was 0.88 in favor of experimental arm (95% CI 0.85-0.91; p<0.0001). Heterogeneity was not significant (Cochran's Q 2.11, p=0.3, I2 index 5.2%). Adverse events (AEs), in particular those of grade 3-4, mostly occurred in mTOR-I+HT arm. Combination therapy of HT plus mTOR-I improves the outcome of metastatic luminal breast cancer patients. Our results provide evidence of a class-effect of these targeting molecules. PMID- 26895474 TI - Quasi In Situ Polymerization To Fabricate Copper Nanowire-Based Stretchable Conductor and Its Applications. AB - Stretchable electronics have progressed greatly and have found their way into various applications, thus resulting in a growing demand for high-quality stretchable conductors. Poly(dimethylsiloxane) (PDMS) is the mostly frequently exploited elastomeric substrate for the construction of a stretchable and conductive platform because of its valuable features, such as superb stretch ability, high transparency, and reliable biocompatibility. However, the weak adhesion between the PDMS substrate and the conductive components has always been an intractable issue which undermines the good and stable performance of the resultant devices. We proposed a quasi in situ polymerization method to effectively build a tight and stable attachment between copper nanowire (Cu NW) and the PDMS substrate. The Cu NWs/PDMS conductors show excellent conductivity and antioxidation stability (R/R0 < 1.4 for 50 days in air), enhanced interface adhesion, and stretch ability (80% strain, R/R0 ~ 5), without any complicated preconfiguration of the PDMS substrates. For application demonstration, the Cu NWs/PDMS conductor was deployed as the stretchable electric wiring to illuminate a light-emitting diode. Furthermore, a stretchable capacitive strain sensor was fabricated using the Cu NWs/PDMS as electrodes. The sensor possessed a gauge factor of 0.82 and the minimum detection limit of 1% strain. PMID- 26895473 TI - Involvement of SULF2 in y-irradiation-induced invasion and resistance of cancer cells by inducing IL-6 expression. AB - Cancer cells that survive radiotherapy often display enhanced invasiveness and resistance to death stimuli. Previous findings have suggested that ionizing radiation (IR) induces such undesirable effects by stimulating the STAT3/Bcl-XL pathway. To identify novel cellular components that mediate these actions of IR, we irradiated lung cancer cells with sublethal doses of y-rays and screened for the induction of IR-responsive genes by microarray analysis. The genes encoding 2 extracellular proteins, SULF2 and IL-6, were found to be upregulated, and these results were confirmed by polymerase chain reactions and western blot analyses. Because the IR-mediated induction of SULF2 was a novel finding, we also confirmed the phenomenon in vivo using xenograft tumors in mice. Analyses of signaling processes revealed that IR induced SULF2 expression via p53, which then promoted IL-6 expression by stabilizing beta-catenin, followed by stimulation of the STAT3/Bcl-XL pathway. Consistently, both SULF2 and IL-6 mediated IR-induced invasion and resistance to death stimuli. To investigate whether SULF2 contributes to IR-induced tumor metastasis, we irradiated tumors in mice with sublethal doses of IR. This treatment promoted the entry of tumor cells into the blood stream (intravasation), which was abolished by downregulating SULF2 expression in tumor cells. These results demonstrated that SULF2 can mediate the detrimental effects of IR in vivo. Therefore, SULF2 may be potentially used as a therapeutic and diagnostic target to predict and overcome the malignant effects of IR, particularly in tumors expressing p53 wild-type. PMID- 26895475 TI - Hereditary angioedema in a Jordanian family with a novel missense mutation in the C1-inhibitor N-terminal domain. AB - Hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE) is an autosomal dominant disease caused by mutations in the SERPING1 gene. A Jordanian family, including 14 individuals with C1-INH-HAE clinical symptoms, was studied. In the propositus and his parents, SERPING1 had four mutations leading to amino acid substitutions. Two are known polymorphic variants (c.167T>C; p.Val34Ala and c.1438G>A; p.Val458Met), the others are newly described. One (c.203C>T; p.Thr46Ile) is located in the N-terminal domain of the C1-inhibitor protein and segregates with angioedema symptoms in the family. The other (c.800C>T; p.Ala245Val) belongs to the serpin domain, and derives from the unaffected father. DNA from additional 24 family members were screened for c.203C>T mutation in the target gene. All individuals heterozygous for the c.203C>T mutation had antigenic and functional plasma levels of C1-inhibitor below 50% of normal, confirming the diagnosis of type I C1-INH-HAE. Angioedema symptoms were present in 14 of 16 subjects carrier for the c.203T allele. Among these subjects, those carrying the c.800T variation had more severe and frequent symptoms than subjects without this mutation. This family-based study provides the first evidence that multiple amino acid substitutions in SERPING1 could influence C1-INH-HAE phenotype. PMID- 26895476 TI - Complement gene variants determine the risk of immunoglobulin-associated MPGN and C3 glomerulopathy and predict long-term renal outcome. AB - BACKGROUND: Membranoproliferative glomerulonephritis (MPGN) is an uncommon cause of chronic nephropathy recently reclassified into immunoglobulin-associated MPGN (Ig-MPGN) and C3 glomerulopathy (C3G). In this study we aimed: (1) to evaluate the complement genetic and biochemical profile in patients with Ig-MPGN/C3G; (2) to investigate whether genetic variants and different patterns of complement activation (i.e., fluid versus solid phase) correlate with disease manifestations and outcomes. METHODS: In 140 patients with idiopathic Ig-MPGN or C3G we performed complement biochemical and genetic screening and correlated genetic, biochemical and histology data with clinical features. RESULTS: Mutations in genes encoding alternative pathway complement proteins were found in both Ig-MPGN and C3G, and mutations in the two components of the C3 convertase are the most prevalent. We also report a mutation in THBD encoding thrombomodulin in a C3G patient. The presence of mutations alone does not significantly increase the risk of Ig-MPGN or C3G, but it does so when combined with common susceptibility variants (CD46 c.-366A in Ig-MPGN; CFH V62 and THBD A473 in C3G). Finally, patients without complement gene mutations or C3NeFs--autoantibodies that stabilize the alternative pathway C3 convertase--have a higher risk of progressing to end-stage renal disease than patients with identified mutations and/or C3NeFs, suggesting the existence of different pathogenetic mechanisms that lead to renal disease. CONCLUSIONS: We provide new insights into the pathogenesis of Ig-MPGN/C3G that underscore the complex nature of these diseases and suggest that the current C3G classification may miss many cases associated with abnormalities of the complement alternative pathway. PMID- 26895477 TI - Does the concept of resilience contribute to understanding good quality of life in the context of epilepsy? AB - A significant body of research highlights negative impacts of epilepsy for individual quality of life (QOL). Poor seizure control is frequently associated with reporting of poor QOL and good seizure control with good QOL; however, this is not a universal finding. Evidence suggests that some people enjoy good QOL despite ongoing seizures while others report poor QOL despite good seizure control. Understanding the factors that influence QOL for people with epilepsy and the processes via which such factors exert their influence is central to the development of interventions to support people with epilepsy to experience the best possible QOL. We present findings of a qualitative investigation exploring influences and processes on QOL for people with epilepsy. We describe the clinical, psychological, and social factors contributing to QOL. In particular, we focus on the value of the concept of resilience for understanding quality of life in epilepsy. Based on our analysis, we propose a model of resilience wherein four key component sets of factors interact to determine QOL. This model reflects the fluid nature of resilience that, we suggest, is subject to change based on shifts within the individual components and the interactions between them. The model offers a representation of the complex influences that act and interact to either mitigate or further compound the negative impacts of epilepsy on individual QOL. PMID- 26895478 TI - Erratum To: Spontaneous rupture of a renal artery pseudoaneurysm in a previously hypertensive patient. AB - [This corrects the article DOI: 10.1186/s40885-014-0011-4.]. PMID- 26895479 TI - The use of personal hair dye and its implications for human health. AB - Hair dye products now represent one of the most rapidly growing beauty and personal care industries as both men and women commonly change hair color to enhance youth and beauty and to follow fashion trends. Irrespective of economic and education status, people dye their hair to emphasize the importance given to appearance. Despite adverse reactions, many people continue dyeing mainly for cosmetic purposes. This paper provides a comprehensive review on various aspects of hair dying products, especially with respect to the hair-coloring process, classification, chemical ingredients, possible human health impacts, and regulations. Permanent hair dye, which is the most commonly used product type, is formed by an oxidative process involving arylamines to bring about concerns with long-term exposure. Hence, significant efforts have been put to understand the possible side effects of such exposure including cancer risk. However, hair dyes and their ingredients are mainly identified to have moderate to low acute toxicity such as the cause of allergic contact dermatitis. Although some hair dye components are reported to be carcinogenic in animals, such evidence is not consistent enough in the case of human studies. Consequently, further research is desirable to critically address the significance of this issue, especially with respect to the safety of hair dye ingredients. PMID- 26895480 TI - A Scalable Synthesis of alpha-L-Threose Nucleic Acid Monomers. AB - Recent advances in polymerase engineering have made it possible to copy information back and forth between DNA and artificial genetic polymers composed of TNA (alpha-L-threofuranosyl-(3',2') nucleic acid). This property, coupled with enhanced nuclease stability relative to natural DNA and RNA, warrants further investigation into the structural and functional properties of TNA as an artificial genetic polymer for synthetic biology. Here, we report a highly optimized chemical synthesis protocol for constructing multigram quantities of TNA nucleosides that can be readily converted to nucleoside 2'-phosphoramidites or 3'-triphosphates for solid-phase and polymerase-mediated synthesis, respectively. The synthetic protocol involves 10 chemical transformations with three crystallization steps and a single chromatographic purification, which results in an overall yield of 16-23% depending on the identity of the nucleoside (A, C, G, T). PMID- 26895481 TI - Preparation of core-shell Ag@CeO2 nanocomposite by LSPR photothermal induced interface reaction. AB - The core-shell structure of Ag@CeO2 was prepared by a novel and facile method, which was based on the photothermal effect of localized surface plasmon resonance (LSPR). Nanoparticles (NPs) of Ag were dispersed in a solution containing citric acid, ethylene glycol and cerium nitrate, then under irradiation, Ag NPs generated heat from LSPR and the heat-induced polymerization reaction in the interface between Ag and the sol resulted in cerium gel formation only on the surface of the Ag NPs. After calcination, Ag@CeO2 was successfully obtained, then Ag@CeO2/SiO2 was prepared by loading Ag@CeO2 on SiO2. The resultant catalyst exhibited favorable activity and stability for CO oxidation. The preparation method proposed here should be extendable to other composites with metallic cores and oxide shells in which the metallic nanoparticle possesses LSPR properties. PMID- 26895482 TI - Recent Advance in Tumor-associated Carbohydrate Antigens (TACAs)-based Antitumor Vaccines. AB - Cancer cells can be distinguished from normal cells by displaying aberrant levels and types of carbohydrate structures on their surfaces. These carbohydrate structures are known as tumor-associated carbohydrate antigens (TACAs). TACAs were considered as promising targets for the design of anticancer vaccines. Unfortunately, carbohydrates alone can only evoke poor immunogenicity because they are unable to induce T-cell-dependent immune responses, which is critical for cancer therapy. Moreover, immunotolerance and immunosuppression are easily induced by using natural occurring TACAs as antigens due to their endogenous property. This review summarizes the recent strategies to overcome these obstacles: (1) covalently coupling TACAs to proper carriers to improve immunogenicity, including clustered or multivalent conjugate vaccines, (2) coupling TACAs to T-cell peptide epitopes or the built-in adjuvant to form multicomponent glycoconjugate vaccines, and (3) developing vaccines based on chemically modified TACAs, which is combined with metabolic engineering of cancer cells. PMID- 26895483 TI - Finger gnosis predicts a unique but small part of variance in initial arithmetic performance. AB - Recent studies indicated that finger gnosis (i.e., the ability to perceive and differentiate one's own fingers) is associated reliably with basic numerical competencies. In this study, we aimed at examining whether finger gnosis is also a unique predictor for initial arithmetic competencies at the beginning of first grade-and thus before formal math instruction starts. Therefore, we controlled for influences of domain-specific numerical precursor competencies, domain general cognitive ability, and natural variables such as gender and age. Results from 321 German first-graders revealed that finger gnosis indeed predicted a unique and relevant but nevertheless only small part of the variance in initial arithmetic performance (~1%-2%) as compared with influences of general cognitive ability and numerical precursor competencies. Taken together, these results substantiated the notion of a unique association between finger gnosis and arithmetic and further corroborate the theoretical idea of finger-based representations contributing to numerical cognition. However, the only small part of variance explained by finger gnosis seems to limit its relevance for diagnostic purposes. PMID- 26895484 TI - Understanding eCBT-I - Knowing is half the battle. PMID- 26895485 TI - Feeding Ecology of Northeast Atlantic Mackerel, Norwegian Spring-Spawning Herring and Blue Whiting in the Norwegian Sea. AB - The Norwegian spring-spawning (NSS) herring (Clupea harengus), blue whiting (Micromesistius poutassou) and Northeast Atlantic (NEA) mackerel (Scomber scombrus) are extremely abundant pelagic planktivores that feed in the Norwegian Sea (NS) during spring and summer. This study investigated the feeding ecology and diet composition of these commercially important fish stocks on the basis of biological data, including an extensive set of stomach samples in combination with hydrographical data, zooplankton samples and acoustic abundance data from 12 stock monitoring surveys carried out in 2005-2010. Mackerel were absent during the spring, but had generally high feeding overlap with herring in the summer, with a diet mainly based on calanoid copepods, especially Calanus finmarchicus, as well as a similar diet width. Stomach fullness in herring diminished from spring to summer and feeding incidence was lower than that of mackerel in summer. However, stomach fullness did not differ between the two species, indicating that herring maintain an equally efficient pattern of feeding as mackerel in summer, but on a diet that is less dominated by copepods and is more reliant on larger prey. Blue whiting tended to have a low dietary overlap with mackerel and herring, with larger prey such as euphausiids and amphipods dominating, and stomach fullness and feeding incidence increasing with length. For all the species, feeding incidence increased with decreasing temperature, and for mackerel so did stomach fullness, indicating that feeding activity is highest in areas associated with colder water masses. Significant annual effects on diet composition and feeding-related variables suggested that the three species are able to adapt to different food and environmental conditions. These annual effects are likely to have an important impact on the predation pressure on different plankton groups and the carrying capacity of individual systems, and emphasise the importance of regular monitoring of pelagic fish diets. PMID- 26895487 TI - Correction: Enigmatic Fossils from the Lower Carboniferous Shrimp Bed, Granton, Scotland. PMID- 26895486 TI - Urodynamic findings in amyotrophic lateral sclerosis patients with lower urinary tract symptoms: Results from a pilot study. AB - AIMS: To determine lower urinary tract symptoms (LUTS) prevalence and urodynamic findings in amyotrophic lateral sclerosis (ALS) patients treated in our hospital. METHODS: Cross-sectional and descriptive study on a cohort of ALS patients. Validated questionnaires (ICIQ-SF, IPSS, and OAB-V8) were self-administered in order to evaluate the presence of LUTS. Symptoms were classified as clinically significant (csLUTS), if any of following scores, IPSS > 7, ICIQ-SF > 0, or OAB V8 >= 8, were present. Urodynamic study was offered to csLUTS patients. Physical examination and prostate ultrasound were also performed. RESULTS: Fifty five of seventy nine (70%) ALS patients accepted to participate in the study. Only 24/55 (43.6%) patients met criteria for csLUTS and 13 patients reported urgency urinary incontinence (26.3%). Most of csLUTS patients complained of mixed symptoms (82.6%). QoL measured by IPSS was 2.1 +/- 1.5, 20% scoring as mostly dissatisfied or unhappy. Average QoL ICIQ-SF scoring was 3.17 +/- 3, 33% complained of moderate to severe bother. Ten of twenty four (41.7%) csLUTS patients consented to UDS. The most frequent finding was detrusor overactivity with obstruction due to non-relaxing external sphincter (five patients) or bladder neck (two patients). Two patients showed normal bladder filling but non-relaxing external sphincter during voiding. UDS was normal in one patient. CONCLUSIONS: In this small pilot study we found a high prevalence of csLUTS in ALS which are mainly related to a combination of voiding and storage symptoms. In most patients, symptoms are caused by overactive detrusor combined with non-relaxing sphincter. Severity of symptoms and impact in QoL is only moderate but in a subset of patients can be considerable. Neurourol. Urodynam. 36:626-631, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 26895488 TI - The role of postoperative Tc-99m pertechnetate scintigraphy in estimation of remnant mass and prediction of successful ablation in patients with differentiated thyroid cancer. AB - OBJECTIVE: Surgery and radioactive iodine (RAI) ablation constitute the mainstay of the treatment of differentiated thyroid carcinoma (DTC). In this study, we aimed to evaluate the diagnostic value of postoperative early Tc-99m pertechnetate scanning to detect remnant thyroid tissue and predict ablation success. METHODS: DTC patients evaluated with postoperative Tc-99m pertechnetate scintigraphy and treated with RAI between January 2007 and December 2014 were recruited. The results of Tc-99m pertechnetate scanning were compared with therapeutic I-131 whole-body scanning (TxWBS) and diagnostic I-131 whole-body scanning (DxWBS) performed 6-9 months after RAI. RESULTS: There were 154 (21.5%) male and 563 (78.5%) female patients, with a mean age of 49.11+/-12.35 years. Postoperative Tc-99m pertechnetate scanning was positive in 499 patients (69.6%) and negative in 218 (30.4%) patients. There were 673 (93.9%) patients with a positive TxWBS scan and 44 (6.1%) patients with negative TxWBS scan. Considering TxWBS as the standard test, sensitivity, specificity, positive predictive value, and negative predictive value of Tc-99m pertechnetate scanning were 72.2, 70.5, 97.4, and 14.2%, respectively. DxWBS was positive in 57 (9.0%) and negative in 564 (91%) patients. Ablation dose was higher and preablation thyroglobulin was lower in patients with negative DxWBS (P=0.001 and 0.04, respectively). Overall, 171 (92.9%) of 184 patients with negative Tc-99m pertechnetate had negative DxWBS. CONCLUSION: Postoperative Tc-99m pertechnetate scintigraphy has a high positive predictive value to detect remnant tissue in patients with DTC. Although negative Tc-99m pertechnetate scanning does not indicate removal of all thyroid tissue, it is related to successful ablation in more than 90% of patients. PMID- 26895489 TI - Graphene-Supported Mesoporous Carbons Prepared with Thermally Removable Templates as Efficient Catalysts for Oxygen Electroreduction. AB - Graphene-supported mesoporous carbons with rich nitrogen self-doped active sites (N-MC/rGO) are prepared by direct pyrolysis of a graphene-oxide-supported polymer composite embedded with massive, evenly distributed amorphous FeOOH that serve as efficient thermally removable templates. The resulting N-MC/rGO catalysts exhibit high surface areas and apparent electrocatalytic activity for oxygen reduction reaction in alkaline media. Among the series, the sample prepared at 800 degrees C displays the best performance with a more positive onset potential, higher limiting currents, much higher stability, and stronger poison resistance than commercial Pt/C. This is ascribed to the synergetic functions of the highly conductive graphene support and the mesoporous N-doped carbons that effectively impede the restacking of the graphene sheets and enhance the exposure of the rich nitrogen self-doped active sites. PMID- 26895491 TI - Effect of increased protein intake on the risk of female infertility. PMID- 26895490 TI - Different EV enrichment methods suitable for clinical settings yield different subpopulations of urinary extracellular vesicles from human samples. AB - Urine sample analysis is irreplaceable as a non-invasive method for disease diagnosis and follow-up. However, in urine samples, non-degraded protein and RNA may be only found in urinary extracellular vesicles (uEVs). In recent years, various methods of uEV enrichment using low volumes of urine and unsophisticated equipment have been developed, with variable success. We compared the results of the differential ultracentrifugation procedure with 4 of these methods. The methods tested were a lectin-based purification, Exoquick (System Biosciences), Total Exosome Isolation from Invitrogen and an in-house modified procedure employing the Exosomal RNA Kit from Norgen Biotek Corp. The analysis of selected gene transcripts and protein markers of extracellular vesicles (EVs) revealed that each method isolates a different mixture of uEV protein markers. In our conditions, the extraction with Norgen's reagent achieved the best performance in terms of gene transcript and protein detection and reproducibility. By using this method, we were able to detect alterations of EVs protein markers in urine samples from prostate cancer adenoma patients. Taken together, our results show that the isolation of uEVs is feasible from small volumes of urine and avoiding ultracentrifugation, making easier the analysis in a clinical facility. However, caution should be taken in the selection of the enrichment method since they have a differential affinity for protein uEVs markers and by extension for different subpopulation of EVs. PMID- 26895492 TI - A Statewide Nested Case-Control Study of Preterm Birth and Air Pollution by Source and Composition: California, 2001-2008. AB - BACKGROUND: Preterm birth (PTB) has been associated with exposure to air pollution, but it is unclear whether effects might vary among air pollution sources and components. OBJECTIVES: We studied the relationships between PTB and exposure to different components of air pollution, including gases and particulate matter (PM) by size fraction, chemical composition, and sources. METHODS: Fine and ultrafine PM (respectively, PM2.5 and PM0.1) by source and composition were modeled across California over 2000-2008. Measured PM2.5, nitrogen dioxide, and ozone concentrations were spatially interpolated using empirical Bayesian kriging. Primary traffic emissions at fine scale were modeled using CALINE4 and traffic indices. Data on maternal characteristics, pregnancies, and birth outcomes were obtained from birth certificates. Associations between PTB (n = 442,314) and air pollution exposures defined according to the maternal residence at birth were examined using a nested matched case-control approach. Analyses were adjusted for maternal age, race/ethnicity, education and neighborhood income. RESULTS: Adjusted odds ratios for PTB in association with interquartile range (IQR) increases in average exposure during pregnancy were 1.133 (95% CI: 1.118, 1.148) for total PM2.5, 1.096 (95% CI: 1.085, 1.108) for ozone, and 1.079 (95% CI: 1.065, 1.093) for nitrogen dioxide. For primary PM, the strongest associations per IQR by source were estimated for onroad gasoline (9 11% increase), followed by onroad diesel (6-8%) and commercial meat cooking (4 7%). For PM2.5 composition, the strongest positive associations per IQR were estimated for nitrate, ammonium, and secondary organic aerosols (11-14%), followed by elemental and organic carbon (2-4%). Associations with local traffic emissions were positive only when analyses were restricted to births with residences geocoded at the tax parcel level. CONCLUSIONS: In our statewide nested case-control study population, exposures to both primary and secondary pollutants were associated with an increase in PTB. CITATION: Laurent O, Hu J, Li L, Kleeman MJ, Bartell SM, Cockburn M, Escobedo L, Wu J. 2016. A statewide nested case control study of preterm birth and air pollution by source and composition: California, 2001-2008. Environ Health Perspect 124:1479-1486; http://dx.doi.org/10.1289/ehp.1510133. PMID- 26895493 TI - NMR-based metabonomic analysis of normal rat urine and faeces in response to (+/ )-venlafaxine treatment. AB - (+/-)-Venlafaxine, a bicyclic antidepressant of the serotonin-norepinephrine reuptake inhibitor (SNRI) class, is prescribed for the treatment of depression and anxiety disorders. As is the case with other antidepressants, its precise mechanisms of action are still unknown. Pharmacometabonomic approaches allow for the detection of diverse metabolites, unlike classic methods for analysing drug interaction based on single metabolites and linear pathways. This provides a global view of the state of homeostasis during treatment and an insight into the mechanisms of action of a drug. Accordingly, the final outcome of treatment is characterised by the network of reactome pathways derived from the on-target and off-target effects of the drug. Regarding antidepressants, the drug network may be located in the gut-microbiome-brain-liver-kidney-immune-cardiovascular system axis (GMBLKICA), implying that neurotransmitters participate as signalling molecules in bidirectional communication. If their bioavailability is increased, this communication and the state of homeostasis may be disrupted. With a pharmacometabonomic approach using NMR in combination with different chemometric methods, a determination was made of subtle changes in the metabolic profile (metabotype) of urine and faeces in normal Wistar rats following a single administration of pharmacological doses of (+/-)-venlafaxine hydrochloride. Based on the drug-response metabotypes observed, (+/-)-venlafaxine had effects on gut microbial co-metabolites and osmolytes. Hence, it can be hypothesized that bidirectional communication in the multiorgan axis was perturbed by this drug, and very likely by its active metabolite, (+/-)-desvenlafaxine. This disrupted signalling could be related not only to therapeutic and adverse effects, but also to the lag period in treatment response. PMID- 26895494 TI - Hydrophilic interaction liquid chromatography in analysis of granisetron HCl and its related substances. Retention mechanisms and method development. AB - In this paper separation of granisetron and its two related substances in HILIC mode is presented. Separation was done on silica column derivatized with sulfoalkylbetaine groups (ZIC-HILIC). Firstly, retention mechanisms were assessed whereby retention factors of substances were followed in wide range of acetonitrile content (80-97%), at constant concentration of aqueous buffer (10mM) as well as at constant pH value of 3.0. Further, in order to developed optimal HILIC method, Design of Experiments (DoE) methodology was applied. For optimization full factorial design 3(2) was employed. Influence of acetonitrile content and ammonium acetate concentration were investigated while pH of the water phase was kept at 3.3. Adequacy of obtained mathematical models was confirmed by ANOVA. Optimization goals (alpha>1.15 and minimal run time) were accomplished with 94.7% of acetonitrile in mobile phase and 70 mM of ammonium acetate in water phase. Optimal point was in the middle of defined Design Space. In the next phase, robustness was experimetally tested by Rechtschaffen design. The investigated factors and their levels were: acetonitrile content (+/-1%), ammonium acetate molarity in water phase (+/-2 mM), pH value of water phase (+/ 0.2) and column temperature (+/-4 degrees C). The validation scope included selectivity, linearity, accuracy and precision as well as determination of limit of detection (LOD) and limit of quantification (LOQ) for the related substances. Additionally, the validation acceptance criteria were met in all cases. Finally, the proposed method could be successfully utilized for estimation of granisetron HCl and its related substances in tablets and parenteral dosage forms, as well as for monitoring degradation under various stress conditions. PMID- 26895495 TI - Development of a reliable method based on ultra-performance liquid chromatography coupled to tandem mass spectrometry to measure thiol-associated oxidative stress in whole blood samples. AB - The aminothiols are biological compounds with numerous vital functions. One of the most relevant is their role as antioxidant systems. The reduced to oxidized ratios are extremely useful indicators of oxidative stress and cellular redox status. We have validated an ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) method to determine the levels of glutathione, cysteine, homocysteine, and their respective oxidized compounds in whole blood samples. Results showed excellent linearity for all the analytes with correlation coefficients between 0.990 and 0.997, suitable precision with intra day coefficient of variation <=20%, and satisfactory accuracy with recoveries between 75 and 130%. The limits of detection in whole blood samples were 1.16 nmol L(-1) for glutathione, 115.8 nmol L(-1) for oxidized glutathione, 9.3 nmol L(-1) for homocystine, 92.6 nmol L(-1) for homocysteine, 347 nmol L(-1) for cystine and 0.23 nmol L(-1) for cysteine. The suitability of the method was ascertained in whole blood samples (n=80) from a consolidated experimental model of hypoxia-reoxygenation in newborn piglets. PMID- 26895496 TI - Application of a novel liquid chromatography/tandem mass spectrometry method for the determination of antazoline in human plasma: Result of ELEPHANT-I [ELEctrophysiological, pharmacokinetic and hemodynamic effects of PHenazolinum (ANTazoline mesylate)] human pharmacokinetic study. AB - Antazoline is a first-generation antihistaminic agent with antiarrhythmic quinidine-like properties. In some countries, it is widely used for termination of cardiac arrhythmias, especially atrial fibrillation (AF). However, no human pharmacokinetic studies have been conducted with intravenous antazoline. The aim of our study was to develop and validate a novel liquid chromatography/tandem mass spectrometry (LC-MS/MS) method for the determination of antazoline in human plasma: the ELEPHANT-I [ELEctrophysiological, pharmacokinetic and hemodynamic effects of PHenazolinum (ANTazoline mesylate)] human pharmacokinetic study. Antazoline was extracted from plasma using liquid-liquid extraction. The concentration of the analyte was measured by LC-MS/MS with xylometazoline as an internal standard. The method was validated for linearity, precision, accuracy, stability (freeze/thaw stability, stability in autosampler, short and long term stability), dilution integrity and matrix effect. The analyzed validation criteria were fulfilled. The method was applied to a pharmacokinetic study involving 10 healthy volunteers. Following a single intravenous dose of antazoline mesylate (100 mg), the plasma concentration profile showed a relative fast elimination with a terminal elimination half-life of 2.29 h. A relatively high volume of distribution was observed (Vss=315 L). The values of mean residence time (MRTinfinity), area under the curve (AUCinfinity) and clearance were 3.45 h, 0.91 mg h L(-1) and 80.5 L h(-1), respectively. One volunteer showed significant differences in pharmacokinetic parameters. In conclusion, the proposed new LC-MS/MS method was successfully used for the first time for the determination of antazoline in human plasma. PMID- 26895497 TI - Near infrared spectroscopic transmittance measurements for pharmaceutical powder mixtures. AB - This study describes the development of near infrared (NIR) calibration models using transmittance measurements in powder samples and compares the results obtained with those of tablet transmittance and diffuse reflectance of powders. Transmission near infrared spectroscopy is a method widely used for the analysis of tablets in the evaluation of drug concentration due to the larger sample volume analyzed, but not commonly used for the analysis of powder samples. Diffuse reflection near infrared spectroscopy is a method used in both powder and tablets for the evaluation of quality attributes. In this initial study NIR transmittance measurements were obtained using an off-line spectrometer equipped with a high intensity light source. Spectra were obtained with three different resolutions for the analysis of powder and tablet samples of 7.50-22.50% (w/w) acetaminophen. The Partial Least Squares (PLS) calibration models developed include pretreatments such as Standard Normal Variate (SNV) and first derivative in the region from 9500-7500 cm(-1). Transmittance in powder presented low Root Mean Square Error of Prediction (RMSEP) values that varied from 0.23-1.15% (w/w) APAP with resolution of 64 and 16 cm(-1). The lowest RMSEP values (0.23-0.39% (w/w) APAP) were obtained using a resolution of 64 cm(-1). The RMSEP values for powder transmittance measurements were 2.4-5.6 times lower than the diffuse reflectance measurements of the powder mixtures. PMID- 26895498 TI - Rosiglitazone Promotes Bone Marrow Adipogenesis to Impair Myelopoiesis under Stress. AB - OBJECTIVE: The therapeutic use of thiazolidinediones (TZDs) causes unwanted hematological side effects, although the underlying mechanisms of these effects are poorly understood. This study tests the hypothesis that rosiglitazone impairs the maintenance and differentiation of hematopoietic stem/progenitor cells, which ultimately leads to hematological abnormalities. METHODS: Mice were fed a rosiglitazone-supplemented diet or a normal diet for 6 weeks. To induce hematopoietic stress, all mice were injected once with 250 mg/kg 5-fluorouracil (5-Fu) intraperitoneally. Next, hematopoietic recovery, hematopoietic stem/progenitor cells (HSPCs) subsets, and myeloid differentiation after 5-Fu treatment were evaluated. The adipogenesis induced by rosiglitazone was assessed by histopathology and oil red O staining. The effect of adipocytes on HSPCs was studied with an in vitro co-culture system. RESULTS: Rosiglitazone significantly enhanced bone marrow adipogenesis and delayed hematopoietic recovery after 5-Fu treatment. Moreover, rosiglitazone inhibited proliferation of a granulocyte/monocyte progenitor (GMP) cell population and granulocyte/macrophage colony-stimulating factor (GM-CSF) colonies, although the proliferation and mobilization of Lin-c-kit+Sca-1+ cells (LSK) was maintained following hematopoietic stress. These effects could be partially reversed by the selective PPARgamma antagonist BADGE. Finally, we demonstrated in a co-culture system that differentiated adipocytes actively suppressed the myeloid differentiation of HSPCs. CONCLUSION: Taken together, our results demonstrate that rosiglitazone inhibits myeloid differentiation of HSPCs after stress partially by inducing bone marrow adipogenesis. Targeting the bone marrow microenvironment might be one mechanism by which rosiglitazone impairs stress-induced hematopoiesis. PMID- 26895499 TI - Transcatheter Closure of Atrial Septal Defects using the GORE((r)) Septal Occluder in Children Less Than 10 kg of Body Weight. AB - The GORE((r)) Septal Occluder (GSO) is a well-evaluated device for interventional ASD closure with closure rates comparable to the Amplatzer((r)) Septal Occluder (ASO), but there are no published reports of its use in small children weighing less than 10 kg. This may be due to the necessity of a large-sized introducing sheath of at least 10 Fr and therefore the assumed risk of complications in vascular access. The GSO is an alternative option for interventional ASD closure in children weighing less than 10 kg. Fourteen infants and children with a median body weight 8900 g (range 6350-9650 g) underwent successful ASD closure using the GSO. The closure was performed under fluoroscopic and transthoracic echocardiographic guidance. Postprocedure, the vessels passed by the occluder and delivery catheter were examined by duplex sonography. The median ASD diameter was 11 mm (5-17 mm), and the median GSO size was 22.5 mm (15-30 mm), whereas the median ASO left disc size that would have been recommended was 25 mm (17-31 mm). All ASDs were successfully closed. During a median follow-up of 1.57 years (range 0.5-4.2), no complications like erosion, embolization, arrhythmias, or vascular injuries occurred. Although using a 10-Fr introducer sheath, no vascular complications were detected. Our data suggest that the small usable size as well as the soft and flexible design of the device allows successful use of the GSO in young children. PMID- 26895500 TI - Lumbar discal cyst as a cause of radiculopathy: case report. AB - Lumbar discal cysts are rare entities causing radicular pain with unknown etiologies. We report a case of a 42-year-old man who developed radiculopathy secondary to a lumbar discal cyst. Our case sheds some light on anatomy, possible etiological association and clinical course which can help management. PMID- 26895501 TI - Enhancing proliferation and osteogenic differentiation of HMSCs on casein/chitosan multilayer films. AB - Creating a bioactive surface is important in tissue engineering. Inspired by the natural calcium binding property of casein (CA), multilayer films ((CA/CS)n) with chitosan (CS) as polycation were fabricated to enhance biomineralization, cell adhesion and differentiation. LBL self-assembly technique was used and the assembly process was intensively studied based on changes of UV absorbance, zeta potential and water contact angle. The increasing content of chitosan and casein with bilayers was further confirmed with XPS and TOF-SIMS analysis. To improve the biocompatibility, gelatin was surface grafted. In vitro mineralization test demonstrated that multilayer films had more hydroxyapatite crystal deposition. Human mesenchymal stem cells (HMSCs) were seeded onto these films. According to fluorescein diacetate (FDA) and cell cytoskeleton staining, MTT assay, expression of osteogenic marker genes, ALP activity, and calcium deposition quantification, it was found that these multilayer films significantly promoted HMSCs attachment, proliferation and osteogenic differentiation than TCPS control. PMID- 26895502 TI - Tea tree oil nanoemulsions for inhalation therapies of bacterial and fungal pneumonia. AB - Tea tree oil (TTO) is a natural essential oil with strong antimicrobial efficacy and little drug resistance. However, the biomedical applications of TTO are limited due to its hydrophobicity and formulation problems. Here, we prepared an inhalable TTO nanoemulsion (nanoTTO) for local therapies of bacterial and fungal pneumonia. The optimal formulation of nanoTTOs consisted of TTO/Cremophor EL/water with a mean size of 12.5nm. The nanoTTOs showed strong in vitro antimicrobial activities on Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae, Staphylococcus aureus and Candida albicans. After inhalation to the lung, the nanoTTOs had higher anti-fungal effect than fluconazole on the fungal pneumonia rat models with reduced lung injury, highly microbial clearance, blocking of leukocyte recruitment, and decrease of pro-inflammatory mediators. In the case of rat bacterial pneumonia, the nanoTTOs showed slightly lower therapeutic efficacy than penicillin though at a much lower dose. Taken together, our results show that the inhalable nanoTTOs are promising nanomedicines for local therapies of fungal and bacterial pneumonia with no obvious adverse events. PMID- 26895503 TI - Carbamate-linked cationic lipids with different hydrocarbon chains for gene delivery. AB - A series of carbamate-linked cationic lipids containing saturated or unsaturated hydrocarbon chains and quaternary ammonium head were designed and synthesized. After recrystallization, carbamate-linked cationic lipids with high purity (over 95%) were obtained. The structures of these lipids were proved by IR spectrum, HR ESI-MS, HPLC, (1)H NMR and (13)C NMR. The liposomes were prepared by using these cationic lipids and neutral lipid DOPE. Particle size and zeta-potential were studied to show that they were suitable for gene transfection. The DNA-bonding ability of C12:0, C14:0 and C18:1 cationic liposomes was much better than others. The results of transfection showed that hydrophobic chains of these lipids have great effects on their transfection activity. The lipids bearing C12:0, C14:0 saturated chains or C18:1 unsaturated chain showed relatively higher transfection efficiency and lower cytotoxicity. So these cationic lipids could be used as non viral gene carriers for further studies. PMID- 26895504 TI - On the accessibility of surface-bound drugs on magnetic nanoparticles. Encapsulation of drugs loaded on modified dextran-coated superparamagnetic iron oxide by beta-cyclodextrin. AB - We report the loading of drugs on aminoethylaminodextran-coated iron oxide nanoparticles, their superparamagnetic behavior, loading of drugs on them, and the beta-cyclodextrin-complex formation of the drugs on the surface of the nanoparticles. The magnetic behavior is studied using vibrating sample magnetometry and X-ray photoelectron spectroscopy is used to analyze the elemental composition of drug-loaded nanoparticles. Scanning electron microscopy shows ordered structures of drug-loaded nanoparticles. UV-visible absorption and fluorescence spectroscopy are used to study the binding of the surface-loaded drugs to beta-cyclodextrin. All of the drugs form 1:1 host-guest complexes. The iodide ion quenching of fluorescence of free- and iron oxide-attached drugs are compared. The binding strengths of the iron oxide surface-loaded drugs-beta cyclodextrin binding are smaller than those of the free drugs. PMID- 26895505 TI - Vitamin E TPGS conjugated carbon nanotubes improved efficacy of docetaxel with safety for lung cancer treatment. AB - The aim of this work was to develop multi-walled carbon nanotubes (MWCNT), which were coated or covalently conjugated with d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS), and loaded docetaxel as a model drug for effective treatment to lung cancer in comparison with the commercial docetaxel injection (DocelTM). The human lung cancer cells (A549 cells) were employed as an in-vitro model to access cellular uptake, cytotoxicity, cellular apoptosis, cell cycle analysis, and reactive oxygen species (ROS) study of the docetaxel/coumarin-6 loaded MWCNT. The safety of MWCNT formulations were studied by the measurements of alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and total protein levels in bronchoalveolar lavage (BAL) fluid of rats after the treatments. The IC50 values demonstrated that the TPGS conjugated MWCNT could be 80 folds more effective than DocelTM after 24h treatment with the A549 cells. Flow cytometry analysis confirmed that cancerous cells were appeared significantly (P<0.05) in the sub G1 phase for TPGS conjugated MWCNT. Results of TPGS conjugated MWCNT have showed better efficacy with safety than non-coated or TPGS coated MWCNT and DocelTM. PMID- 26895506 TI - Collisions and coalescence in droplet streams for the production of freeze-dried powders. AB - Streams of mono-disperse micro-droplets with diameters ranging from about 20 MUm to 100 MUm were produced from diluted aqueous solutions containing carbohydrates and proteins using a pinhole type piezoelectric generator with either a 20 MUm or a 50 MUm single-orifice diaphragm. Image sequences indicating droplet size, velocity, inter-droplet spacing at various distances from the nozzles as well as collision events and coalescence were recorded using a high-speed camera and analysed quantitatively. The size-dependent gradual deceleration of the droplets is superimposed by small scale random movements, which equally affect both large and small droplets and lead to early contacts and coalescence. The loss of mono dispersity can be reduced by quick cooling since both the nucleation rate and the freezing rate of micro-droplets are extremely dependent upon the temperature of their gaseous environment. PMID- 26895507 TI - Innovative hybrid vs polymeric nanocapsules: The influence of the cationic lipid coating on the "4S". AB - Polymeric and hybrid aqueous-core nanocapsules were prepared using a low energy organic-solvent free procedure as innovative nanodevices for the ophthalmic delivery of melatonin. In order to evaluate how different cationic lipids could affect the main properties of the nanodevices, we focused our attention on mean particles size, surface charge, shape and stability (the "4S"). The results of our study confirmed the hypothesis that the coating material differently affects the overall nanoparticles properties, above all in terms of morphology: in particular, the cationic lipid dimethyldioctadecylammonium bromide allows the formation of very stable well-defined nanocapsules with non-spherical shape with sustained and prolonged drug release, thus representing a great advantage in ophthalmic application. PMID- 26895508 TI - New p32/gC1qR Ligands for Targeted Tumor Drug Delivery. AB - Cell surface p32, the target of LyP-1 homing peptide, is upregulated in tumors and atherosclerotic plaques and has been widely used as a receptor for systemic delivery of payloads. Here, we identified an improved LyP-1-mimicking peptide (TT1, CKRGARSTC). We used this peptide in a fluorescence polarization-based high throughput screening of a 50,000-compound chemical library and identified a panel of compounds that bind p32 with low micromolar affinity. Among the hits identified in the screen, two compounds were shown to specifically bind to p32 in multiple assays. One of these compounds was chosen for an in vivo study. Nanoparticles surface-functionalized with this compound specifically adhered to surfaces coated with recombinant p32 and, when injected intravenously, homed to p32-expressing breast tumors in mice. This compound provides a lead for the development of p32-targeted affinity ligands that circumvent some of the limitations of peptide-based probes in guided drug delivery. PMID- 26895509 TI - Texture Descriptors Ensembles Enable Image-Based Classification of Maturation of Human Stem Cell-Derived Retinal Pigmented Epithelium. AB - AIMS: A fast, non-invasive and observer-independent method to analyze the homogeneity and maturity of human pluripotent stem cell (hPSC) derived retinal pigment epithelial (RPE) cells is warranted to assess the suitability of hPSC-RPE cells for implantation or in vitro use. The aim of this work was to develop and validate methods to create ensembles of state-of-the-art texture descriptors and to provide a robust classification tool to separate three different maturation stages of RPE cells by using phase contrast microscopy images. The same methods were also validated on a wide variety of biological image classification problems, such as histological or virus image classification. METHODS: For image classification we used different texture descriptors, descriptor ensembles and preprocessing techniques. Also, three new methods were tested. The first approach was an ensemble of preprocessing methods, to create an additional set of images. The second was the region-based approach, where saliency detection and wavelet decomposition divide each image in two different regions, from which features were extracted through different descriptors. The third method was an ensemble of Binarized Statistical Image Features, based on different sizes and thresholds. A Support Vector Machine (SVM) was trained for each descriptor histogram and the set of SVMs combined by sum rule. The accuracy of the computer vision tool was verified in classifying the hPSC-RPE cell maturation level. DATASET AND RESULTS: The RPE dataset contains 1862 subwindows from 195 phase contrast images. The final descriptor ensemble outperformed the most recent stand-alone texture descriptors, obtaining, for the RPE dataset, an area under ROC curve (AUC) of 86.49% with the 10-fold cross validation and 91.98% with the leave-one-image-out protocol. The generality of the three proposed approaches was ascertained with 10 more biological image datasets, obtaining an average AUC greater than 97%. CONCLUSIONS: Here we showed that the developed ensembles of texture descriptors are able to classify the RPE cell maturation stage. Moreover, we proved that preprocessing and region-based decomposition improves many descriptors' accuracy in biological dataset classification. Finally, we built the first public dataset of stem cell-derived RPE cells, which is publicly available to the scientific community for classification studies. The proposed tool is available at https://www.dei.unipd.it/node/2357 and the RPE dataset at http://www.biomeditech.fi/data/RPE_dataset/. Both are available at https://figshare.com/s/d6fb591f1beb4f8efa6f. PMID- 26895510 TI - Which HIV patients should be screened for osteoporosis: an international perspective. AB - PURPOSE OF REVIEW: This review provides international insights into the real world clinical approach to screening for bone mineral density (BMD) and osteoporosis in people living with HIV (PLWH) using opinions from HIV physicians from key regions around the world. RECENT FINDINGS: Although a significant proportion of PLWH are aged over 50, the relative importance of low BMD to clinical care differs significantly between countries and regions, based on factors such as the population at risk, access to adequate screening resources, and physicians' knowledge. Generally, management of osteoporosis in PLWH follows similar principals as for the general population, with risk factors for fracture combined with measurement of BMD by dual energy X-ray absorptiometry in algorithms such as Fracture Risk Assessment Tool, designed to provide an overall risk estimation. Although in most regions age is considered among the most important factors contributing to low BMD and fractures, considerable country and region-specific factors become apparent, such as malnutrition, inactivity and impact of comorbidities, substance abuse, and increasing use of tenofovir disoproxil fumarate. SUMMARY: These opinions highlight the diversity that still exists in the approach to the long-term management of PLWH and highlight challenges facing development of consensus guidelines that can be effectively implemented worldwide. PMID- 26895511 TI - CD4+ and CD8+ CD28(null) T Cells Are Cytotoxic to Autologous Muscle Cells in Patients With Polymyositis. AB - OBJECTIVE: Inflammatory T cell infiltrates in the skeletal muscle tissue of patients with polymyositis are dominated by CD28-negative effector (CD28(null) ) T cells of both the CD4 and CD8 lineage. These cells are potentially cytotoxic, and the aim of the present study was to develop a fully autologous cell culture system in which to investigate the functional contribution of such CD28(null) T cells to myotoxicity. METHODS: In vitro cocultures of autologous skeletal muscle cells and T cell subsets obtained from 5 polymyositis patients were performed. Myotoxicity of T cells was quantified by calcein release and flow cytometric analyses. T cell degranulation was blocked with concanamycin A. Specific blocking of perforin, cytokines, and HLA was performed using antibodies. RESULTS: Both CD4+CD28(null) and CD8+CD28(null) T cells induced more muscle cell death than did their CD28+ counterparts. Differentiated muscle cells (myotubes) were more sensitive to T cell-mediated cell death than were their precursors (myoblasts). Both CD8+ and CD4+ CD28(null) T cells displayed perforin polarization toward muscle cells and secreted higher levels of granzyme B and interferon-gamma (IFNgamma) in coculture than did CD28+ T cells. The myotoxic effects of CD28(null) T cells were reduced upon the blocking of perforin, cytokines, and HLA. Addition of IFNgamma or tumor necrosis factor did not induce skeletal muscle cell death in the absence of T cells; however, it did up-regulate HLA expression on muscle cells. CONCLUSION: Myotoxicity of CD4+ and CD8+ CD28(null) T cells is mediated by directed perforin-dependent killing and can be further influenced by IFNgamma-induced HLA expression on muscle cells. The data suggest that CD28(null) T cells are key effector cells that contribute to the muscle cell damage in polymyositis. PMID- 26895512 TI - [Congenital Malformations of the Hand]. PMID- 26895513 TI - [Strategies in Treatment of Congenital Hand Malformation]. AB - The aim of the treatment of congenital hand anomalies is to achieve a functional improvement in order to enable patients to lead an independent life. As parents have to decide for their children early in life, they have to be convinced of the treatment proposal. One and the same disease may present with various individual pathologies, which may require intraoperative changes of the previously planned procedure. Because of possible changes during growth, doctors have to keep in touch with the patients up to the end of adolescence. This article presents our algorithm and surgical techniques for dealing with children with hand malformations. PMID- 26895514 TI - Clinical Presentation, Surgical Treatment, and Outcome in Radial Polydactyly. AB - Radial polydactyly or 'thumb duplication' is the most common congenital upper limb anomaly ('CULA') affecting the thumb. The clinical presentation is highly diverse, ranging from an extra thumb floating on a skin bridge to complicated thumb triplications with triphalangeal, deviating, and hypoplastic components. Radial polydactyly can be classified into one of 7 osseous presentations using the Wassel classification, with type IV (45%), type II (20%), and type VII (15%) occurring most frequently. When faced with a radial polydactyly case, hand surgeons specialised in congenital anomalies must weigh the preoperative functional potential and degree of hypoplasia of both thumbs in order to decide whether to resect one thumb and reconstruct the other ('resection and reconstruction'), excise a central part of both thumbs and unite the lateral tissues into one thumb ('the Bilhaut procedure'), transfer the better-developed distal tissues of one thumb onto the better-developed proximal tissues of the other ('on-top plasty'), or discard both severely hypoplastic thumbs and pollicise the index finger. Mere excision of the hypoplastic thumb is rarely indicated since it often requires subsequent revision surgery. Even after being treated by experienced surgeons, about 15% of patients with polydactyly will need additional procedures to correct residual and/or new problems such as deviation from the longitudinal axis and joint instability. Nevertheless, radial polydactyly patients usually achieve unimpaired everyday hand function postoperatively. PMID- 26895515 TI - [Correction of the Thumb in Apert Syndrome - Modified Dome Osteotomy and Bilobed Flap]. AB - Children with Apert syndrome have extensive malformations of the extremities and the head. The thumb in Apert syndrome is always short with radial deviation and the first web space is narrowed and flattened. These thumbs can be corrected in a simple manner by modified dome osteotomy of the proximal phalanx combined with soft tissue coverage using a bilobed flap with simultaneous widening of the first web space. A preoperative multi-slice computed tomography (MSCT) angiography scan helps in planning the surgical procedures. This article describes the surgical technique and the results in 6 hands of 3 children. The aim is to illustrate the correction of the axis and length of the thumb. PMID- 26895516 TI - [Differential Diagnoses of Trigger Thumb]. AB - Trigger thumb is one of the most common hand pathologies in toddlers. Its differential diagnoses are thumb-in-palm deformity, hyperflexible thumb, thumb hypoplasia, and congenital stiffness of the distal interphalangeal joint of the thumb. This article describes typical clinical signs of these different diseases in order to enable surgeons to make the correct diagnosis leading to the right treatment. PMID- 26895517 TI - [A Simple Surgical Procedure to Correct Palmar Instability of the Metacarpophalangeal Joint of the Thumb in Children]. PMID- 26895518 TI - [Specific Characteristics of Trigger Finger in Children]. AB - BACKGROUND: Trigger finger in children is a rare condition with relevant differences to the more frequent trigger thumb in children and the very frequent trigger finger in adults. PATIENTS AND METHODS: In a retrospective analysis of children who underwent surgery for trigger fingers in 2 specialised centres, we evaluated 42 children with a total of 63 trigger fingers. Due to persistent triggering after release of the A1 pulley based on intraoperative findings in 12 children with a mean age of 3.7 years ranging from 0.6 to 10.2 years and a total of 17 trigger fingers, additional measures after the release of the A1 pulley were required, mainly the resection of one limb of the sublimis tendon. In one of these children another simultaneously operated finger required the release of the A1 pulley alone. We performed a retrospective chart review of these patients and evaluated the results after a mean follow-up time of 4.8 years ranging from 1.2 to 11.8 years by phone call. Functional impairments, persistent pain, satisfaction and complications were monitored. RESULTS: All patients treated with A1 pulley release and resection of one limb of the sublimis tendon had excellent results. One patient had a recurrence and another patient developed a contracture of the PIP joint. In both patients, the widening of the tendon sheath had been done by A2 pulley enlargement in addition to the A1 pulley release. CONCLUSIONS: Persistent triggering of a finger following the release of the A1 pulley in a child can be successfully treated by resection of one limb of the sublimis tendon. PMID- 26895519 TI - [Epiphyseal Bar Resection for Correction of Clinodactyly]. AB - BACKGROUND: Clinodactyly is a digital angulation in the radio-ulnar plane. Mostly it is seen on the little finger. The middle phalanx typically has a triangular or trapezoid shape (delta phalanx), resulting in radial deviation of the distal phalanx. Resection of the longitudinal epiphyseal bracket (physiolysis) with fat graft interposition is a possible surgical technique, which uses children's growth potential to correct the axial deviation. AIM: The purpose of our study was to review the degree of correction at least 2 years postoperatively and after an average of 5 years postoperatively, and to find out if children's age influences the results. PATIENTS AND METHODS: 23 children (43 little fingers) underwent physiolysis and were retrospectively analyzed after a median follow-up of 5 years (2.1-7.9 years). The active range of motion of the little finger's MP, PIP and DIP joints and finger-palm-distance were measured. Lateral deviation was determined by using standardized radiographs and subsequently compared with preoperative values. Patients were divided into 2 subgroups: younger than 3 years (16 fingers, group A), older than 3 years (27 fingers, group B). The achieved correction of the lateral deviation was compared between both groups. RESULTS: All patients showed full active range of motion in all joints of treated fingers. Finger-palm-distance was 0 cm. No complications occurred. The mean preoperative deviation of all patients was 37 degrees +/-11, which improved after surgery by 17 degrees +/-11 (i. e. 44.0%+/-23.1 of initial findings). Group A demonstrated a mean preoperative lateral deviation of 40 degrees +/-9, and group B a mean deviation of 36 degrees +/-12. In both groups we saw a similar improvement (group A mean: 17 degrees +/-10, group B mean: 17 degrees +/-11). In group A there was a wider dispersion of postoperative results. In the age group 7 to 10, the results of individual cases show the large variability of the corrective potential. X rays revealed the following incidental findings after surgery: a premature fusion of the proximal radial epiphyseal plates in 2 fingers and a sinuous-shaped proximal radial epiphyseal plate in 12 other fingers. CONCLUSION: Resection of the longitudinal epiphyseal bracket with fat graft interposition is a technically simple and effective treatment option for clinodactyly, particularly in children of 3 to 6 years of age. PMID- 26895520 TI - [Distraction Osteogenesis is an Effective Method to Lengthen Digits in Congenital Malformations]. AB - PURPOSE: The aim of this study was to investigate the feasible amount of lengthening by distraction osteogenesis in congenital hand deficiencies. PATIENTS AND METHODS: A total of 60 patients (1.6-17.8 years) underwent lengthening of 71 bones between 1994 and 2014. Bone lengthening was performed on 46 metacarpals and 25 phalanges. Mostly the first (n=30) and the fifth (n=21) rays were lengthened. Bone lengthening was performed to treat primarily symbrachydactyly (b=32) and amniotic band syndrome (n=10). To analyze the amount of lengthening preoperative radiographs and radiographs taken while removing the external fixator were compared. The charts were reviewed regarding age at surgery, duration of lengthening, duration of bony consolidation, complication, etc. RESULTS: The average of metacarpal distraction was 18.4 mm=73% lengthening with respect to the preoperative length; the average of phalange distraction was 14.0 mm=77% of the preoperative length. In both, metacarpals and phalanges, a lengthening of > 100% of the preoperative bone length was possible. In target length was reached in 89% of the procedures. The average time for consolidation was 6.1 (1-20) days/mm lengthening. The external fixator was in use on average for 140 (50-346) days. After removing of the external fixator an axial K-wire was used to stabilize the callus in 9 procedure, and an iliac bone craft plus axial K-wire in 11 procedures. The rate of complications was 30% (early consolidation, deviation, joint dislocation, pin infection, tendon dislocation). All complications could be treated without with acceptable results. CONCLUSION: Metacarpal and phalangeal distraction lengthening is an effective but demanding technique for ray reconstruction in congenital malformations of the hand. It is possible to lengthen a bone by more than 100%. Complications are common, but in most cases easy to handle. PMID- 26895521 TI - [Congenital Fibrosarcoma of the Left Index Finger - An Unusual Case]. AB - Congenital fibrosarcoma is a rare mesenchymal soft tissue tumour, which most commonly develops in the peripheral extremities during infancy. Diagnostic work up is a challenge for clinicians and pathologists alike, because in many cases the lesion initially resembles a haemangioma on macroscopic inspection. A 4-month old boy presented with a strongly vascularised tumour of the left index finger, which had been diagnosed as a capillary haemangioma by means of a biopsy performed in another facility. The lesion had been treated with systemic and intralesional cortisone injections. Due to ulceration and the risk of infection, the tumour mass was resected with the index finger being preserved. The histological appearance was inconclusive. PCR revealed a congenital fibrosarcoma. 2 years after surgery, the boy is free from recurrence. PMID- 26895522 TI - Biography of Norton J. Greenberger, MD. PMID- 26895523 TI - In the United States, "Opt-Out" States Show No Increase in Access to Anesthesia Services for Medicare Beneficiaries Compared with Non-"Opt-Out" States. AB - In the United States, anesthesia care can be provided by anesthesiologists or nurse anesthetists. Since 2001, 17 states have exercised their right to "opt-out" of the federal requirement that a physician supervise the administration of anesthesia by a nurse anesthetist, with the majority citing increased access to anesthesia care as the rationale for their decision. By using Medicare data, we found that most (4 of 5) cohorts of "opt-out" states likely experienced smaller growth in anesthesia utilization rates compared with non-"opt-out" states, suggesting that opt-out was not associated with an increase in access to anesthesia care. PMID- 26895524 TI - Glu106 targeted inhibitors of ORAI1 as potential Ca2+ release-activated Ca2+ (CRAC) channel blockers - molecular modeling and docking studies. AB - Calcium release-activated calcium modulator 1(ORAI1) is an integral component of the calcium release-activated calcium channel (CRAC) channel complex and plays a central role in regulating Ca2 + concentrations in T-lymphocytes. It is critical for many physiological processes, including cell-proliferation, cytokine production and activation of the immune system. Loss of ORAI1 function is linked with rheumatoid arthritis (RA) and hence pharmacological blockers of ORAI1 could be potential therapeutic agents for the treatment of RA. In this study, we have used a high-throughput screening approach to inhibit the binding of Ca2+ toward ORAI1 and the interactions are verified through induced fit docking. The results hint that these compounds act by possibly binding with, and thereby blocking Ca2+ binding with ORAI1 (E106). The molecular dynamics (MD) simulations shows strong support toward the hit compounds by showing the ligand potency throughout the simulation timescale of 30 ns. We have thus identified a novel class of highly stable, potential lead compounds that directly bind with the selectivity filter region E106 and block Ca2+ binding on ORAI1. This resulting alteration in the pore geometry of ORAI1 due to the strong blocking mechanism of lead compounds will greatly diminish its function and the downstream activities that result from the same including decreased production of cytokines in autoimmune disorders. This study may lay the foundation for finding novel lead compounds for clinical trials that could positively modulate the course of autoimmune disorders with ORAI1 as its specific target. PMID- 26895525 TI - Letter to the Editor: High-grade spinal cord glioma. PMID- 26895526 TI - Vertebral compression fractures after stereotactic body radiation therapy: a large, multi-institutional, multinational evaluation. AB - OBJECTIVE The purpose of this study was to identify factors contributing to an increased risk for vertebral compression fracture (VCF) following stereotactic body radiation therapy (SBRT) for spinal tumors. METHODS A total of 594 tumors were treated with spinal SBRT as primary treatment or re-irradiation at 8 different institutions as part of a multi-institutional research consortium. Patients underwent LINAC-based, image-guided SBRT to a median dose of 20 Gy (range 8-40 Gy) in a median of 1 fraction (range 1-5 fractions). Median patient age was 62 years. Seventy-one percent of tumors were osteolytic, and a preexisting vertebral compression fracture (VCF) was present in 24% of cases. Toxicity was assessed following treatment. Univariate and multivariate analyses were performed using a logistic regression method to determine parameters predictive for post-SBRT VCF. RESULTS At a median follow-up of 10.1 months (range 0.03-57 months), 80% of patients had local tumor control. At the time of last imaging follow-up, at a median of 8.8 months after SBRT, 3% had a new VCF, and 2.7% had a progressive VCF. For development of any (new or progressive) VCF following SBRT, the following factors were predictive for VCF on univariate analysis: short interval from primary diagnosis to SBRT (less than 36.8 days), solitary metastasis, no additional bone metastases, no prior chemotherapy, preexisting VCF, no MRI used for target delineation, tumor volume of 37.3 cm(3) or larger, equivalent 2-Gy-dose (EQD2) tumor of 41.8 Gy or more, and EQD2 spinal cord Dmax of 46.1 Gy or more. Preexisting VCF, solitary metastasis, and prescription dose of 38.4 Gy or more were predictive on multivariate analysis. The following factors were predictive of a new VCF on univariate analysis: solitary metastasis, no additional bone metastases, and no MRI used for target delineation. Presence of a solitary metastasis and lack of MRI for target delineation remained significant on multivariate analysis. CONCLUSIONS A VCF following SBRT is more likely to occur following treatment for a solitary spinal metastasis, reflecting a more aggressive treatment approach in patients with adequately controlled systemic disease. Higher prescription dose and a preexisting VCF also put patients at increased risk for post-SBRT VCF. In these patients, pre-SBRT cement augmentation could be considered to decrease the risk of subsequent VCF. PMID- 26895527 TI - Long-term clinical outcomes following 3- and 4-level anterior cervical discectomy and fusion. AB - OBJECTIVE The purpose of this study was to report the long-term clinical outcomes following 3- and 4-level anterior cervical discectomy and fusion (ACDF). METHODS A retrospective review of all adult neurosurgical patients undergoing elective ACDF for degenerative disease at a single institution between 1996 and 2013 was performed. Patients who underwent first-time 3- or 4-level ACDF were included; patients with previous cervical spine surgery, those undergoing anterior/posterior approaches, and those with corpectomy were excluded. Outcome measures included perioperative complication rates, fusion rates, need for revision surgery, Nurick Scores, Odom's criteria, symptom resolution, neck visual analog scale (VAS) pain score, and persistent narcotics usage. RESULTS Seventy one patients who underwent 3-level ACDF and 26 patients who underwent 4-level ACDF were identified and followed for an average of 7.6 +/- 4.2 years. There was 1 case (3.9%) of deep wound infection in the 4-level group and 1 case in the 3 level group (1.4%; p = 0.454). Postoperatively, 31% of patients in the 4-level group complained of dysphagia, compared with 12.7% in the 3-level group (p = 0.038). The fusion rate was 84.6% after 4-level ACDF and 94.4% after 3-level ACDF (p = 0.122). At last follow-up, a significantly higher proportion of patients in the 4-level group continued to have axial neck pain (53.8%) than in the 3-level group (31%; p = 0.039); the daily oral morphine equivalent dose was significantly higher in the 4-level group (143 +/- 97 mg/day) than in the 3-level group (25 +/- 10 mg/day; p = 0.030). Outcomes based on Odom's criteria were also different between cohorts (p = 0.044), with a significantly lower proportion of patients in the 4-level ACDF group experiencing an excellent/good outcome. CONCLUSIONS In this study, patients who underwent 4-level ACDF had significantly higher rates of dysphagia, postoperative neck pain, and postoperative narcotic usage when compared with patients who underwent 3-level ACDF. Pseudarthrosis and deep wound infection rates were also higher in the 4-level group, although this did not reach statistical significance. Additionally, a smaller proportion of patients achieved a good/excellent outcome in the 4-level group than in the 3-level group. These findings suggest a significant increase of perioperative morbidity and worsened outcomes for patients who undergo 4- versus 3-level ACDF. PMID- 26895528 TI - Lordoplasty: midterm outcome of an alternative augmentation technique for vertebral fractures. AB - OBJECTIVE Vertebroplasty and balloon kyphoplasty are effective treatment options for osteoporotic vertebral compression fractures but are limited in correction of kyphotic deformity. Lordoplasty has been reported as an alternative, cost effective, minimally invasive, percutaneous cement augmentation technique with good restoration of vertebral body height and alignment. The authors report on its clinical and radiological midterm results. METHODS A retrospective review was conducted of patients treated with lordoplasty from 2002 to 2014. Inclusion criteria were clinical and radiological follow-up evaluations longer than 24 months. Radiographs were accessed regarding initial correction and progressive loss of reduction. Complications and reoperations were recorded. Actual pain level, pain relief immediately after surgery, autonomy, and subjective impression of improvement of posture were assessed by questionnaire. RESULTS Sixty-five patients (46 women, 19 men, age range 38.9-86.2 years old) were treated with lordoplasty for 69 vertebral compression and insufficiency fractures. A significant correction of the vertebral kyphotic angle (mean 13 degrees ) and segmental kyphotic angle (mean 11 degrees ) over a mean follow-up of 33 months (range 24-108 months) was achieved (p < 0.001). On average, pain was relieved to 90% of the initial pain level. In 24% of the 65 patients a second spinal intervention was necessary: 16 distant (24.6%) and 7 adjacent (10.8%) new osteoporotic fractures, 4 instrumented stabilizations (6.2%), 1 new adjacent traumatic fracture (1.5%), and 1 distant microsurgical decompression (1.5%). Cement leakage occurred in 10.4% but was only symptomatic in 1 case. CONCLUSIONS Lordoplasty appeared safe and effective in midterm pain alleviation and restoration of kyphotic deformity in osteoporotic compression and insufficiency fractures. The outcomes of lordoplasty are consistent with other augmentation techniques. PMID- 26895530 TI - Letter to the Editor: Nonpenetrating titanium clips for dural closure during spinal surgery. PMID- 26895529 TI - Modeled cost-effectiveness of transforaminal lumbar interbody fusion compared with posterolateral fusion for spondylolisthesis using N(2)QOD data. AB - OBJECTIVE Transforaminal lumbar interbody fusion (TLIF) has become the most commonly used fusion technique for lumbar degenerative disorders. This suggests an expectation of better clinical outcomes with this technique, but this has not been validated consistently. How surgical variables and choice of health utility measures drive the cost-effectiveness of TLIF relative to posterolateral fusion (PSF) has not been established. The authors used health utility values derived from Short Form-6D (SF-6D) and EQ-5D and different cost-effectiveness thresholds to evaluate the relative cost-effectiveness of TLIF compared with PSF. METHODS From the National Neurosurgery Quality and Outcomes Database (N(2)QOD), 101 patients with spondylolisthesis who underwent PSF were propensity matched to patients who underwent TLIF. Health-related quality of life measures and perioperative parameters were compared. Because health utility values derived from the SF-6D and EQ-5D questionnaires have been shown to vary in patients with low-back pain, quality-adjusted life years (QALYs) were derived from both measures. On the basis of these matched cases, a sensitivity analysis for the relative cost per QALY of TLIF versus PSF was performed in a series of cost assumption models. RESULTS Operative time, blood loss, hospital stay, and 30-day and 90-day readmission rates were similar for the TLIF and PSF groups. Both TLIF and PSF significantly improved back and leg pain, Oswestry Disability Index (ODI) scores, and EQ-5D and SF-6D scores at 3 and 12 months postoperatively. At 12 months postoperatively, patients who had undergone TLIF had greater improvements in mean ODI scores (30.4 vs 21.1, p = 0.001) and mean SF-6D scores (0.16 vs 0.11, p = 0.001) but similar improvements in mean EQ-5D scores (0.25 vs 0.22, p = 0.415) as patients treated with PSF. At a cost per QALY threshold of $100,000 and using SF-6D-based QALYs, the authors found that TLIF would be cost-prohibitive compared with PSF at a surgical cost of $4830 above that of PSF. However, with EQ 5D-based QALYs, TLIF would become cost-prohibitive at an increased surgical cost of $2960 relative to that of PSF. With the 2014 US per capita gross domestic product of $53,042 as a more stringent cost-effectiveness threshold, TLIF would become cost-prohibitive at surgical costs $2562 above that of PSF with SF-6D based QALYs or at a surgical cost exceeding that of PSF by $1570 with EQ-5D derived QALYs. CONCLUSIONS As with all cost-effectiveness studies, cost per QALY depended on the measure of health utility selected, durability of the intervention, readmission rates, and the accuracy of the cost assumptions. PMID- 26895531 TI - Biomechanical evaluation of lumbar pedicle screws in spondylolytic vertebrae: comparison of fixation strength between the traditional trajectory and a cortical bone trajectory. AB - OBJECTIVE In the management of isthmic spondylolisthesis, the pedicle screw system is widely accepted surgical strategy; however, there are few reports on the biomechanical behavior of pedicle screws in spondylolytic vertebrae. The purpose of the present study was to compare fixation strength between pedicle screws inserted through the traditional trajectory (TT) and those inserted through a cortical bone trajectory (CBT) in spondylolytic vertebrae by computational simulation. METHODS Finite element models of spondylolytic and normal vertebrae were created from CT scans of 17 patients with adult isthmic spondylolisthesis (mean age 54.6 years, 10 men and 7 women). Each vertebral model was implanted with pedicle screws using TT and CBT techniques and compared between two groups. First, fixation strength of a single screw was evaluated by measuring axial pullout strength. Next, vertebral fixation strength of a paired screw construct was examined by applying forces simulating flexion, extension, lateral bending, and axial rotation to vertebrae. RESULTS Fixation strengths of TT screws showed a nonsignificant difference between the spondylolytic and the normal vertebrae (p = 0.31-0.81). Fixation strength of CBT screws in the spondylolytic vertebrae demonstrated a statistically significant decrease in pullout strength (21.4%, p < 0.01), flexion (44.1%, p < 0.01), extension (40.9%, p < 0.01), lateral bending (38.3%, p < 0.01), and axial rotation (28.1%, p < 0.05) compared with those in the normal vertebrae. In the spondylolytic vertebrae, no statistically significant difference was observed for pullout strength between TT and CBT (p = 0.90); however, the CBT construct showed lower vertebral fixation strength in flexion (39.0%, p < 0.01), extension (35.6%, p < 0.01), lateral bending (50.7%, p < 0.01), and axial rotation (59.3%, p < 0.01) compared with the TT construct. CONCLUSIONS CBT screws are less optimal for stabilizing the spondylolytic vertebra due to their lower fixation strength compared with TT screws. PMID- 26895532 TI - Management of subaxial cervical instability in very young or small-for-age children using a static single-screw anterior cervical plate: indications, results, and long-term follow-up. AB - OBJECTIVE Subaxial cervical instability in very young or small-for-age children is uncommon and typically arises from trauma or skeletal dysplasia. Various operative techniques have been used to achieve stabilization in pediatric patients with evidence of instability, including anterior, posterior, and combined approaches. In this study, the authors report their results with subaxial cervical instability in this patient population treated using a static single-screw anterior cervical plate (ACP) system and allograft fusion. METHODS In a retrospective chart review, the authors identified all patients 6 years of age or younger who underwent an anterior cervical fusion procedure using a static single-screw ACP system either as a stand-alone construct or as part of an anterior-posterior stabilization procedure. Reasons for fusion included trauma, tumor, and congenital anomalies. RESULTS Five patients 6 years of age or younger underwent anterior cervical fusion using a static single-screw system during the 19-year study period. Follow-up ranged from 12 to 51 months (mean 26.8 months). Two patients underwent repeat surgery, one 7 days after and the other 21 months after their initial procedure. At last follow-up, a mean vertical growth of 22.8% was seen across the fused segments, with no evidence of kyphotic or lordotic abnormalities. CONCLUSIONS In very young or small-for-age children, the use of a static single-screw ACP system appears to be a safe and effective option to manage subaxial cervical instability. Bony fusion and continued longitudinal growth occur within the fused segments, with no evidence of long-term cervical malalignment. PMID- 26895533 TI - Effect of aging on pain relief in the older cancer patients: pharmacokinetic and pharmacodynamic aspects. PMID- 26895534 TI - Evaluation of ELISA testing for BP180 and BP230 as a diagnostic modality for bullous pemphigoid: a clinical experience. AB - Bullous pemphigoid (BP) is a common autoimmune blistering disorder of the elderly. Several diagnostic modalities are available, including clinical impression, histopathology, direct and indirect immunofluorescence, and enzyme linked immunosorbent assay (ELISA) detection of pathogenic antibodies. In this study, we aim to examine the utility of the newest test, ELISA, in comparison to the constellation of other tests. We describe our clinical experience in which 170 patients diagnosed with bullous pemphigoid had multiple tests performed. BP180 alone showed a sensitivity of 54 % and specificity of 94 %. The positive predictive value (PPV) is 95 % while the negative predictive value (NPV) is 52 %. BP230 alone yielded a sensitivity of 48 % and specificity of 94 %. The PPV is 94 % and the NPV is 49 %. Using both tests in combination yielded a sensitivity of 66 % and specificity of 89 %. The PPV of at least one of two tests returning positive is 92 % while the NPV of dual negative tests is 58 %. Use of ELISAs for suspected cases of BP are an inadequate standalone test, and are only helpful in making the diagnosis should they return positive. However, they would appear to miss about one-third of cases. PMID- 26895535 TI - The use of Biochip immunofluorescence microscopy for the serological diagnosis of epidermolysis bullosa acquisita. AB - Epidermolysis bullosa acquisita is a rare autoimmune bullous disease characterized by the presence of circulating antibodies directed against the collagen type VII. Diagnosis is generally based on clinical history, clinical features, histology, direct and indirect immunofluorescence, immunoblotting and ELISA. Our study aims to determine the validity of the Biochip immunofluorescence microscopy for the serological diagnosis of epidermolysis bullosa acquisita. Six patients with epidermolysis bullosa acquisita and presence of antibodies against type VII collagen confirmed by ELISA were included in the study. Subsequently, all sera of patients were analyzed using Biochip. Antibodies anti-collagen type VII were detected in all sera by means of the Biochip technology. Thus, Biochip shows a good correlation with ELISA and seems to be an appropriate method for the diagnosis of epidermolysis bullosa acquisita. It is an easy, fast and standardized method which could facilitate the diagnosis of this autoimmune bullous disease. We suggest that it could be used as an initial screening test to identify patients with epidermolysis bullosa acquisita. PMID- 26895536 TI - Divergent responses of methanogenic archaeal communities in two rice cultivars to elevated ground-level O3. AB - Inhibitive effect of elevated ground-level ozone (O3) on paddy methane (CH4) emission varies with rice cultivars. However, little information is available on its microbial mechanism. For this purpose, the responses of methane-metabolizing microorganisms, methanogenic archaea and methanotrophic bacteria to O3 pollution were investigated in the O3-tolerant (YD6) and the O3-sensitive (IIY084) cultivars at two rice growth stages in Free Air Concentration Elevation of O3 (O3 FACE) system of China. It was found that O3 pollution didn't change the abundances of Type I and Type II methanotrophic bacteria at two rice stages. For methanogenic archaea, their abundances in both cultivars were decreased by O3 pollution at the tillering stage. Furthermore, a greater negative influence on methanogenic archaeal community was observed on IIY084 than on YD6: at tillering stage, the alpha diversity indices of methanogenic archaeal community in IIY084 was decreased to a greater extent than in YD6; IIY084 shifted methanogenic archaeal community composition and decreased the abundances and the diversities of Methanosarcinaceae and Methanosaetaceae as well as the abundance of Methanomicrobiales, while the diversity of Methanocellaceae were increased in YD6. These findings indicate that the variations in the responses of paddy CH4 emission to O3 pollution between cultivars could result from the divergent responses of their methanogenic archaea. PMID- 26895537 TI - Interactive effects of temperature, ultraviolet radiation and food quality on zooplankton alkaline phosphatase activity. AB - Ultraviolet Radiation (UVR) is a stressor for aquatic organisms affecting enzyme activities in planktonic populations because of the increase in reactive oxygen species. In addition, UVR exposure combined with other environmental factors (i.e. temperature and food quality) could have even higher detrimental effects. In this work, we aimed to determine the effect of UVR on somatic Alkaline Phosphatase Activity (APA) and Glutathione S-Transferase (GST) activity on the cladoceran Daphnia commutata under two different temperatures (10 degrees C and 20 degrees C) and under three food qualities (carbon:phosphorus ratios: 1150, 850 and 550). APA is a biomarker that is considered as a P deficiency indicator in zooplankton. Since recovery from UVR damage under dark conditions is an ATP depending reaction we also measured APA during recovery phases. We carried out a laboratory experiment combining different temperatures and food qualities with exposition to UVR followed by luminic and dark phases for recovery. In addition, we exposed organisms to H2O2, to establish if the response on APA to UVR was a consequence of the reactive oxygen species produced these short wavelengths. Our results showed that somatic APA was negatively affected by UVR exposure and this effect was enhanced under high temperature and low food quality. Consistently, GST activity was higher when exposed to UVR under both temperatures. The H2O2 experiments showed the same trend as UVR exposure, indicating that APA is affected mainly by oxidative stress than by direct effect of UVR on the enzyme. Finally, APA was affected in the dark phase of recovery confirming the P demands. These results enlighten the importance of food quality in the interacting effect of UVR and temperature, showing that C:P food ratio could determine the success or failure of zooplanktonic populations in a context of global change. PMID- 26895538 TI - Elevated lead levels and adverse effects on natural killer cells in children from an electronic waste recycling area. AB - Lead (Pb) has been proved to exert immunotoxicity to influence immune homeostasis in humans. To monitor the internal Pb level and evaluate its effect on natural killer (NK) cells and cytokine/chemokine concentrations, we recruited 285 preschool children from Guiyu, one of the largest electronic waste (e-waste) destinations and recycling areas in the world, and known to have high concentrations of Pb in the air, soil, water, sediment and plants. A total of 126 preschool children were selected from Haojiang as a reference group. Results showed that children in Guiyu, the exposed area, had higher blood Pb levels and lower percentages of NK cells than children from the reference area. A significantly negative association was found between the percentage of NK cells and increasing Pb levels. Moreover, children in Guiyu area had higher platelet counts and IL-1beta concentrations, and lower levels of IL-2, IL-27, MIP-1alpha and MIP-1beta were observed in the exposed children. These changes might not be conducive to the development and differentiation of NK cells. Taken together, the elevated Pb levels result in the lower percentages of NK cells, but also alter the levels of platelets, IL-1beta and IL-27, which might be unconducive to the activity and function of NK cells. PMID- 26895539 TI - A case study to optimise and validate the brine shrimp Artemia franciscana immobilisation assay with silver nanoparticles: The role of harmonisation. AB - Brine shrimp Artemia sp. has been recognised as an important ecotoxicity and nanotoxicity test model organism for salt-rich aquatic environments, but currently there is still no harmonised testing protocol which would ensure the comparable results for hazard identification. In this paper we aimed to design the harmonised protocol for nanomaterial toxicity testing using Artemia franciscana and present a case study to validate the protocol with silver nanoparticles (AgNPs). We (i) revised the existing nanotoxicity test protocols with Artemia sp. (ii) optimised certain methodological steps based on the experiments with AgNPs and potassium dichromate (K2Cr2O7) as a soluble reference chemical and (iii) tested the optimised protocol in an international inter laboratory exercise conducted within the EU FP7 NanoValid project. The intra- and inter-laboratory reproducibility of the proposed protocol with a soluble reference chemical K2Cr2O7 was good, which confirms the suitability of this assay for conventional chemicals. However, the variability of AgNPs toxicity results was very high showing again that nanomaterials are inherently challenging for toxicity studies, especially those which toxic effect is linked to shed metal ions. Among the identified sources for this variability were: the hatching conditions, the type of test plate incubation and the illumination regime. The latter induced variations assumingly due to the changes in bioavailable silver species concentrations. Up to our knowledge this is the first inter-laboratory comparison of the Artemia sp. toxicity study involving nanomaterials. Although the inter-laboratory exercise revealed poor repeatability of AgNPs toxicity results, this study provides valuable information regarding the importance of harmonisation of all steps in the test procedure. Also, the presented AgNPs toxicity case study may serve as a platform for further validation steps with other types of NMs. PMID- 26895540 TI - Effect of soil properties, heavy metals and emerging contaminants in the soil nematodes diversity. AB - Among soil organisms, nematodes are seen as the most promising candidates for bioindications of soil health. We hypothesized that the soil nematode community structure would differ in three land use areas (agricultural, forest and industrial soils), be modulated by soil parameters (N, P, K, pH, SOM, CaCO3, granulometric fraction, etc.), and strongly affected by high levels of heavy metals (Cd, Pb, Zn, Cr, Ni, Cu, and Hg) and emerging contaminants (pharmaceuticals and personal care products, PPCPs). Although these pollutants did not significantly affect the total number of free-living nematodes, diversity and structure community indices vastly altered. Our data showed that whereas nematodes with r-strategy were tolerant, genera with k-strategy were negatively affected by the selected pollutants. These effects diminished in soils with high levels of heavy metals given their adaptation to the historical pollution in this area, but not to emerging pollutants like PPCPs. PMID- 26895542 TI - 3D Bioprinting of Tissue/Organ Models. AB - In vitro tissue/organ models are useful platforms that can facilitate systematic, repetitive, and quantitative investigations of drugs/chemicals. The primary objective when developing tissue/organ models is to reproduce physiologically relevant functions that typically require complex culture systems. Bioprinting offers exciting prospects for constructing 3D tissue/organ models, as it enables the reproducible, automated production of complex living tissues. Bioprinted tissues/organs may prove useful for screening novel compounds or predicting toxicity, as the spatial and chemical complexity inherent to native tissues/organs can be recreated. In this Review, we highlight the importance of developing 3D in vitro tissue/organ models by 3D bioprinting techniques, characterization of these models for evaluating their resemblance to native tissue, and their application in the prioritization of lead candidates, toxicity testing, and as disease/tumor models. PMID- 26895541 TI - The Early Worm Catches the Bird? Productivity and Patterns of Trichobilharzia szidati Cercarial Emission from Lymnaea stagnalis. AB - Digenean trematodes are common and abundant in aquatic habitats and their free living larvae, the cercariae, have recently been recognized as important components of ecosystems in terms of comprising a significant proportion of biomass and in having a potentially strong influence on food web dynamics. One strategy to enhance their transmission success is to produce high numbers of cercariae which are available during the activity peak of the next host. In laboratory experiments with 13 Lymnaea stagnalis snails infected with Trichobilharzia szidati the average daily emergence rate per snail was determined as 2,621 cercariae, with a maximum of 29,560. During a snail's lifetime this summed up to a mass equivalent of or even exceeding the snail's own body mass. Extrapolated for the eutrophic pond where the snails were collected, annual T. szidati biomass may reach 4.65 tons, a value equivalent to a large Asian elephant. Emission peaks were observed after the onset of illumination, indicating emission synchronizing with the high morning activities of the definitive hosts, ducks. However, high cercarial emission is possible throughout the day under favorable lightning conditions. Therefore, although bird schistosomes, such as T. szidati constitute only a fraction of the diverse trematode communities in the studied aquatic ecosystem, their cercariae can still pose a considerable risk for humans of getting cercarial dermatitis (swimmer's itch) due to the high number of cercariae emitted from infected snails. PMID- 26895543 TI - Total synthesis and antiproliferative/cytotoxic profiling of 2-epi-jaspine B. AB - A straightforward access to 2-epi-jaspine B (4.HCl) has been developed. Key to the approach was the use of Overman rearrangement for the instalment of a stereocentre bearing a nitrogen atom. Subsequent rational execution of the stereoselective transformations furnished the functionalized scaffold 38, whose coupling with a lipophilic segment under Wittig conditions, followed by deprotection and a THF core construction, completed the convergent synthesis of 2 epimer of 1. The final anhydrophytosphingosine 4.HCl was screened for its antiproliferative/cytotoxic activity employing multiple human cancer cell lines. In vitro evaluation revealed that 2-epi-jaspine B exhibited significant antitumour growth inhibitory activity against all used cells. PMID- 26895544 TI - Variations of pH as an additional tool in the analysis of crowded NMR spectra of fucosylated chondroitin sulfates. AB - The influence of pH variation on chemical shift values in NMR spectra of fucosylated chondroitin sulfates was studied using polysaccharides isolated from three sea cucumber species Apostichopus japonicus, Actinopyga mauritiana and Cucumaria japonica. The signals of glucuronic acid residues were found to be the most sensitive to pH changes in comparison to the chemical shifts of the sulfated galactosamine and fucosyl units, most of which were altered insignificantly. It was shown that in the presence of imidazole-HCl buffer (pH 7.2) NMR spectra of the polysaccharides from A. japonicus and A. mauritiana were sufficiently resolved, whereas under acidic conditions their (1)H NMR spectra were complicated by overlapping of H-1 signals of GlcA and GalNAc. In the case of polysaccharide from C. japonica bearing 3-O-fucosylated and 3-O-sulfated glucuronic acid residues in the backbone, acidification of the medium led to separation of H-1 signals of GlcA3S and GalNAc. Therefore, the combination of data obtained at different pH values may be useful for interpretation of overcrowded spectra of fucosylated chondroitin sulfates. PMID- 26895545 TI - Alkoxyallene-ynes: Selective Preparation of Bicyclo[5.3.0] Ring Systems Including a delta-Alkoxy Cyclopentadienone. AB - The development of an intramolecular rhodium(I)-catalyzed Pauson-Khand reaction of alkoxyallene-ynes with a proximal alkoxy group is reported. This reaction, in the presence of a [Rh(cycloocta-1,5-diene)Cl]2/propane-1,3 diylbis(diphenylphosphane) system under a CO atmosphere, constitutes a powerful tool for selectively accessing carbo- and heterobicyclo[5.3.0] frameworks featuring an enol ether moiety. Through this procedure, a straightforward access to guaiane skeletons with a tertiary hydroxy group at the C10 position was achieved. PMID- 26895547 TI - Posttraumatic Stress Disorder Symptom Severity and Relationship Functioning Among Partnered Heterosexual and Lesbian Women Veterans. AB - PURPOSE: Few studies have examined associations of posttraumatic stress disorder (PTSD) and relationship satisfaction among women Veterans, and no research has explored these factors in lesbian women Veterans, a large subgroup that may have unique concerns. This study examined the link between PTSD and relationship satisfaction in partnered heterosexual and lesbian women Veterans and evaluated potential moderation by sexual orientation, partner support, and conflict. METHODS: Women Veterans (heterosexual n = 260; lesbian n = 128) were recruited nationally to complete a cross-sectional online survey. Multiple linear regression models were used to evaluate moderation, using two- and three-way interactions. RESULTS: Partner support moderated the association between PTSD symptoms and relationship satisfaction to a different degree for heterosexual and lesbian women Veterans, playing a more prominent role in this association for lesbian women. Specifically, for lesbians with low partner support, as PTSD symptoms worsened, relationship satisfaction decreased at a steeper rate than for heterosexual women with low partner support. On the other hand, for lesbians with high partner support, as PTSD symptoms worsened, relationship satisfaction decreased less sharply than for heterosexual women with high partner support. Degree of conflict was highly correlated with relationship satisfaction and also appeared to moderate these relations differently by sexual orientation. CONCLUSION: These findings suggest that women Veterans with PTSD experience impairments in their romantic relationships, which vary by sexual orientation, partner support, and conflict. Partner support and conflict may be important targets in assessment and therapy for women Veterans with PTSD, and especially so for sexual minorities. PMID- 26895546 TI - Intranasal exposure to monoclonal antibody Fab fragments to Japanese cedar pollen Cry j1 suppresses Japanese cedar pollen-induced allergic rhinitis. AB - BACKGROUND AND PURPOSE: Fab fragments (Fabs) of antibodies have the ability to bind to specific allergens but lack the Fc portion that exerts effector functions via binding to receptors including FcepsilonR1 on mast cells. In the present study, we investigated whether intranasal administration of the effector function lacking Fabs of a monoclonal antibody IgG1 (mAb, P1-8) to the major allergen Cry j1 of Japanese cedar pollen (JCP) suppressed JCP-induced allergic rhinitis in mice. EXPERIMENTAL APPROACH: Balb/c mice sensitized with JCP on days 0 and 14 were challenged intranasally with the pollen on days 28, 29, 30 and 35. Fabs prepared by the digestion of P1-8 with papain were also administered intranasally 15 min before each JCP challenge. KEY RESULTS: Intranasal administration of P1-8 Fabs was followed by marked suppression of sneezing and nasal rubbing in mice with JCP-induced allergic rhinitis. The suppression of these allergic symptoms by P1-8 Fabs was associated with decreases in mast cells and eosinophils and decreased hyperplasia of goblet cells in the nasal mucosa. CONCLUSIONS AND IMPLICATIONS: These results demonstrated that intranasal exposure to P1-8 Fabs was effective in suppressing JCP-induced allergic rhinitis in mice, suggesting that allergen-specific mAb Fabs might be used as a tool to regulate allergic pollinosis. PMID- 26895549 TI - Magnetic-field dependence of strongly anisotropic spin reorientation transition in NdFeO3: a terahertz study. AB - One of the biggest challenges in spintronics is finding how to switch the magnetization of a material. One way of the spin switching is the spin reorientation transition (SRT), a switching of macroscopic magnetization rotated by 90 degrees . The macroscopic magnetization in a NdFeO3 single crystal rotates from Gamma4 to Gamma2 via Gamma24 as the temperature is decreased from 170 to 100 K, while it can be switched back to Gamma4 again by increasing the temperature. However, the precise roles of the magnetic-field induced SRT are still unclear. By using terahertz time-domain spectroscopy (THz-TDS), here, we show that the magnetic-field induced SRT between Gamma4 and Gamma2 is strongly anisotropic, depending on the direction of the applied magnetic field. Our experimental results are well interpreted by the anisotropy of rare-earth Nd(3+) ion. Furthermore, we find that the critical magnetic-field required for SRT can be modified by changing the temperature. Our study suggests that the anisotropic SRT in NdFeO3 single crystal provides a platform to facilitate the potential applications in robust spin memory devices. PMID- 26895550 TI - Pseudotumoral lesion: pathology and follow-up. PMID- 26895548 TI - Pragmatic Language Features of Mothers With the FMR1 Premutation Are Associated With the Language Outcomes of Adolescents and Young Adults With Fragile X Syndrome. AB - PURPOSE: Pragmatic language difficulties have been documented as part of the FMR1 premutation phenotype, yet the interplay between these features in mothers and the language outcomes of their children with fragile X syndrome is unknown. This study aimed to determine whether pragmatic language difficulties in mothers with the FMR1 premutation are related to the language development of their children. METHOD: Twenty-seven mothers with the FMR1 premutation and their adolescent/young adult sons with fragile X syndrome participated. Maternal pragmatic language violations were rated from conversational samples using the Pragmatic Rating Scale (Landa et al., 1992). Children completed standardized assessments of vocabulary, syntax, and reading. RESULTS: Maternal pragmatic language difficulties were significantly associated with poorer child receptive vocabulary and expressive syntax skills, with medium effect sizes. CONCLUSIONS: This work contributes to knowledge of the FMR1 premutation phenotype and its consequences at the family level, with the goal of identifying modifiable aspects of the child's language-learning environment that may promote the selection of treatments targeting the specific needs of families affected by fragile X. Findings contribute to our understanding of the multifaceted environment in which children with fragile X syndrome learn language and highlight the importance of family-centered intervention practices for this group. PMID- 26895551 TI - Atypical enterovirus encephalitis causing behavioral changes and autism-like clinical manifestations: case report. PMID- 26895552 TI - Health checks in general practice: evidence first, not last. AB - Despite being ubiquitous in primary care, there is no accepted consensus on the definition and main components of health checks. They range from periodic health evaluations with a general physician, through the screening and diagnostic tests derived from these visits, to broader screening programs. Health checks may promote a fluid patient-provider relationship, improve the delivery of some preventive measures, and reduce the patient's anxiety. However, they can also expose patients to overdiagnosis and unnecessary interventions. Research on the benefits, harms, and cost-effectiveness of health checks is limited. As a consequence, health checks and screening programs are implemented in several countries and supported by national scientific societies based chiefly on their potential benefits on surrogate outcomes. There is also substantial variability regarding the target population (eg, initial age), tests, or intervals. We call for a rigorous assessment of the net effect of all health checks, taking into consideration common biases (eg, sticky-diagnosis and slippery-linkage biases), patient-important outcomes, potential adverse events, cost-effectiveness, as well as equity and feasibility of the proposed programs. PMID- 26895553 TI - Adequacy of Current State Setbacks for Directional High-Volume Hydraulic Fracturing in the Marcellus, Barnett, and Niobrara Shale Plays. AB - BACKGROUND: There is an increasing awareness of the multiple potential pathways leading to human health risks from hydraulic fracturing. Setback distances are a legislative method to mitigate potential risks. OBJECTIVES: We attempted to determine whether legal setback distances between well-pad sites and the public are adequate in three shale plays. METHODS: We reviewed geography, current statutes and regulations, evacuations, thermal modeling, air pollution studies, and vapor cloud modeling within the Marcellus, Barnett, and Niobrara Shale Plays. DISCUSSION: The evidence suggests that presently utilized setbacks may leave the public vulnerable to explosions, radiant heat, toxic gas clouds, and air pollution from hydraulic fracturing activities. CONCLUSIONS: Our results suggest that setbacks may not be sufficient to reduce potential threats to human health in areas where hydraulic fracturing occurs. It is more likely that a combination of reasonable setbacks with controls for other sources of pollution associated with the process will be required. CITATION: Haley M, McCawley M, Epstein AC, Arrington B, Bjerke EF. 2016. Adequacy of current state setbacks for directional high-volume hydraulic fracturing in the Marcellus, Barnett, and Niobrara Shale Plays. Environ Health Perspect 124:1323-1333; http://dx.doi.org/10.1289/ehp.1510547. PMID- 26895554 TI - External-Field-Induced Growth Effect of an a-C:H Film for Manipulating Its Medium Range Nanostructures and Properties. AB - A special catalytic growth effect (called the "external-field-induced effect") was found to exist on the poisoning target surface during the reactive sputtering process of a-C:H films. Enlightened by this effect, we demonstrate a facile approach to manipulate the medium-range-ordered nanostructure and mechanical and tribological properties of a-C:H films. By adjusting the plasma ionization degree, a graphene precursor was successfully produced at the graphite target surface through the synergistic catalytic effects of both the catalyst and plasma. Then, graphene was further sputtered into amorphous carbon films to form graphene-like nanoclusters. This special graphene-like nanostructure endows the a C:H film with outstanding hardness, high elasticity, and excellent tribological properties. The elastic recovery of the film was improved to 92.5%, and the wear life in a vacuum environment was also prolonged to 8.8 * 10(5) cycles at a contact stress of 0.9 GPa, which suggests that medium-range-ordered clusters in an amorphous carbon matrix provide an important way to improve the properties of carbon films. PMID- 26895556 TI - When the bronchoalveolar lavage makes the diagnosis of interstitial pneumonia. PMID- 26895557 TI - Destruction and recovery of a nanorod conductive network in polymer nanocomposites via molecular dynamics simulation. AB - By adopting coarse-grained molecular dynamics simulation, we investigate the effects of end-functionalization and shear flow on the destruction and recovery of a nanorod conductive network in a functionalized polymer matrix. We find that the end-functionalization of polymeric chains can enhance the electrical conductivity of nanorod filled polymer nanocomposites, indicated by the decrease of the percolation threshold. However, there exists an optimal end functionalization extent to reach the maximum electrical conductivity. In the case of steady shear flow, both homogeneous conductive probability and directional conductive probability perpendicular to the shear direction decrease with the shear rate, while the directional conductive probability parallel to the shear direction increases. Importantly, we develop a semi-empirical equation to describe the change of the homogeneous conductive probability as a function of the shear rate. Meanwhile, we obtain an empirical formula describing the relationship between the anisotropy of the conductive probability and the orientation of the nanorods. In addition, the conductivity stability increases with increasing nanorod volume fraction. During the recovery process of the nanorod conductive network, it can be fitted well by the model combining classical percolation theory and a time-dependent nanorod aggregation kinetic equation. The fitted recovery rate is similar for different nanorod volume fractions. In summary, this work provides some rational rules for fabricating polymer nanocomposites with excellent performance of electrical conductivity. PMID- 26895558 TI - Visual Speech Perception in Children With Language Learning Impairments. AB - PURPOSE: The purpose of the study was to assess the ability of children with developmental language learning impairments (LLIs) to use visual speech cues from the talking face. METHOD: In this cross-sectional study, 41 typically developing children (mean age: 8 years 0 months, range: 4 years 5 months to 11 years 10 months) and 27 children with diagnosed LLI (mean age: 8 years 10 months, range: 5 years 2 months to 11 years 6 months) completed a silent speechreading task and a speech-in-noise task with and without visual support from the talking face. The speech-in-noise task involved the identification of a target word in a carrier sentence with a single competing speaker as a masker. RESULTS: Children in the LLI group showed a deficit in speechreading when compared with their typically developing peers. Beyond the single-word level, this deficit became more apparent in older children. On the speech-in-noise task, a substantial benefit of visual cues was found regardless of age or group membership, although the LLI group showed an overall developmental delay in speech perception. CONCLUSION: Although children with LLI were less accurate than their peers on the speechreading and speech-in noise-tasks, both groups were able to make equivalent use of visual cues to boost performance accuracy when listening in noise. PMID- 26895555 TI - Redox-Annulation of Cyclic Amines and beta-Ketoaldehydes. AB - Benzo[a]quinolizine-2-one derivatives are readily assembled from 1,2,3,4 tetrahydroisoquinoline and beta-ketoaldehydes by means of a new intramolecular redox-Mannich process. These reactions are promoted by simple acetic acid and are thought to involve azomethine ylides as reactive intermediates. PMID- 26895559 TI - Microalbuminuria predicts the recurrence of cardiovascular events in patients with essential hypertension. AB - OBJECTIVES: Microalbuminuria (MAU) is associated with an enhanced risk of cardiovascular events. The prevalence of MAU and its prognostic impact has an important role in the stratification of cardiovascular risk in patients with essential hypertension. This is an observational, prospective study performed by 13 general practitioners aiming at assessing the prevalence and prognostic relevance of MAU in essential hypertension. METHODS: Patients with essential hypertension and with recent determination of MAU were enrolled into the study by general practitioners, and were followed up for 3 years. Primary end point was the occurrence of major cardiovascular events during the follow-up. RESULTS: Out of 1024 unselected patients, consecutively enrolled from January 2009 to March 2010, 804 completed the 3-year follow-up. Patients were categorized into two groups according to the absence (n = 523, 65%) or presence (n = 281, 35%) of MAU. During the follow-up, 41 cardiovascular events (1.69 events/100 patient-years) were reported. The presence of MAU was not associated with increased risk of cardiovascular events (adjusted hazard ratio = 1.32; 95% confidence interval 0.290-4.340, P = 0.097). When the analysis was restricted to the patients with previous cardiovascular event, MAU (adjusted hazard ratio = 2.18; 95% confidence interval 0.42-2.43, P = 0.031), together with age, metabolic syndrome, diabetes, and smoking, independently predicted the occurrence of cardiovascular events. CONCLUSION: Presence of MAU in patients with essential hypertension is not associated with increased risks of cardiovascular events. At the variance, in patients with previous cardiovascular events, MAU was found to predict recurrent events. Thus, the assessment of MAU could be considered a useful tool in secondary prevention. PMID- 26895560 TI - Soluble dipeptidyl peptidase-4 induces microvascular endothelial dysfunction through proteinase-activated receptor-2 and thromboxane A2 release. AB - BACKGROUND: Dipeptidyl peptidase-4 (DPP4) is a key protein in glucose homeostasis and a pharmacological target in type 2 diabetes mellitus. This study explored whether the novel adipokine soluble DPP4 (sDPP4) can cause endothelial dysfunction, an early marker of impaired vascular reactivity. METHOD: Reactivity was studied in mesenteric arteries from 3-month-old female mice, using a small vessel myograph. Thromboxane A2 (TXA2) release was explored in cultured human coronary artery endothelial cells by enzyme immunoassay. RESULTS: Neither the contractility to noradrenaline nor the endothelium-independent relaxations induced by sodium nitroprusside were modified by sDPP4. However, sDPP4 impaired in a concentration-dependent manner the endothelium-dependent relaxation elicited by acetylcholine. The DPP4 inhibitors K579 and linagliptin prevented the defective relaxation induced by sDPP4, as did the protease-activated receptor 2 (PAR2) inhibitor GB83. Downstream of PAR2, the cyclooxygenase (COX) inhibitor indomethacin, the COX2 inhibitor celecoxib or the thromboxane receptors blocker SQ29548 prevented the deleterious effects of sDPP4. Accordingly, sDPP4 triggered the release of TXA2 by endothelial cells, whereas TXA2 release was prevented by inhibiting DPP4, PAR2 or COX. CONCLUSION: In summary, these findings reveal sDPP4 as a direct mediator of endothelial dysfunction, acting through PAR2 activation and the release of vasoconstrictor prostanoids. By interfering with these actions, DPP4 inhibitors might help preserving endothelial function in the context of cardiometabolic diseases. PMID- 26895561 TI - A Comparative Analysis of Preemptive Versus Targeted Sedation on Cardiovascular Stability After High-Risk Cardiac Surgery in Infants. AB - OBJECTIVE: To compare the effect of two sedation practices on cardiovascular stability during the early postoperative period in young infants following cardiac surgery: the routine early use of midazolam infusion (preemptive sedation) and the discretionary use of sedatives tailored to the patient's clinical condition (targeted sedation). DESIGN: Retrospective cohort study with matched controls. SETTING: A 15-bedded pediatric cardiac ICU. PATIENTS: Sedation strategies were compared by matching patients before and after the introduction of a targeted sedation guideline, replacing the existing practice of preemptive sedation. Inclusion criteria were age less than 6 months and cardiopulmonary bypass time greater than 150 minutes. Matching criteria were surgical procedure, age, and duration of cardiopulmonary bypass and cross-clamp. The main outcome was cardiovascular instability, defined by the presence of one of the following criteria in the first 12 hours after PICU admission: 1) simultaneous administration of greater than or equal to two inotropic or vasopressor drugs; 2) administration of greater than 60 mL/kg fluid boluses. Secondary outcomes were: 1) markers of cardiac output adequacy (heart rate, blood pressure, vasoactive inotropic score, urine output, volume of fluid boluses, central venous oxygen saturation, lactate); 2) occurrence of adverse events (cardiac arrest, extracorporeal membrane oxygenation, death); 3) sedatives administered and depth of sedation. INTERVENTIONS: Introduction of a guideline of targeted sedation. MEASUREMENTS AND MAIN RESULTS: Thirty-three patients with preemptive sedation were matched to 33 patients with targeted sedation. Targeted sedation resulted in less frequent oversedation, without compromising cardiovascular stability, as indicated by similar occurrence of cardiovascular instability (68.8% with preemptive sedation vs 62.5% with targeted sedation; p = 0.53) and adverse events, and similar markers of cardiac output adequacy. Although all preemptively sedated patients received an infusion of midazolam in the first 12 hours after surgery, only 19.4% of patients in the targeted sedation group received a sedative infusion (p < 0.001). CONCLUSIONS: Our data suggest that after high-risk cardiac surgery in young infants, routine sedation with midazolam may not prevent low cardiac output syndrome. When accompanied by a careful assessment of level of sedation, routine sedation of infants after high-risk cardiac surgery can be avoided without compromising hemodynamic stability or patient safety. The potential benefit of this approach is reduced exposure to sedative. PMID- 26895563 TI - Scattering Dynamics, Survival, and Dispersal of Dimethyl Methylphosphonate Interacting with the Surface of Multilayer Graphene. AB - We explored the interaction of a molecular beam of dimethyl methylphosphonate with a multilayer graphene surface to better understand the fate of chemical warfare agents in the environment. The experiments were done at surface temperatures between 120 and 900 K and translational energies between 200 and 1500 meV. At the lowest temperatures, the dimethyl methylphosphonate is adsorbed, with the molecules next to the carbon surface held slightly more strongly than the bulk molecular film that grows with continued dosing. We measured the desorption energy for submonolayer coverage using modulated beam techniques and found a value of 290 meV (28 kJ/mol). At higher surface temperatures, where the residence times are very short, we measured the scattering of the dimethyl methylphosphonate as a function of angle and translational kinetic energy. For a surface temperature of 250 K, with translational kinetic energies between 200 and 1500 meV, much of the incident flux has nearly been accommodated by the surface temperature and has no memory of the incident momentum. The internal energy also seems to be at least partially accommodated. As the surface temperature increases, the scattering transitions to direct-inelastic reflection, where much of the incident translational energy is retained, and the intensity of the scattering peaks superspecularly toward glancing final angles. These results demonstrate the efficacy of using kinetic energy controlled molecular beams to probe the interactions of complex organic molecules with well-defined surfaces, extending our fundamental understanding of how the dynamics for such systems crossover from trapping-desorption to direct inelastic scattering. Moreover, these results indicate that simulations that model the dispersal of chemical warfare agents using common interfaces in the environment need to account for multiple bounce trajectories and survival of the impinging molecules. PMID- 26895564 TI - Distributions and accumulation rates of polycyclic aromatic hydrocarbons in the northern Gulf of Mexico sediments. AB - Sediment samples collected from shelf, slope and interior basin of the northern Gulf of Mexico during 2011-2013, 1-3 years after the Deepwater Horizon (DWH) oil spill, were utilized to characterize PAH pollution history, in this region. Results indicate that the concentrations of surface SigmaPAH43 and their accumulation rates vary between 44 and 160 ng g(-1) and 6-55 ng cm(-2) y(-1), respectively. SigmaPAH43 concentration profiles, accumulation rates and Delta(14)C values are significantly altered only for the sediments in the immediate vicinity of the DWH wellhead. This shows that the impact of DWH oil input on deep-sea sediments was generally limited to the area close to the spill site. Further, the PAHs source diagnostic analyses suggest a noticeable change in PAHs composition from higher to lower molecular weight dominance which reflects a change in source of PAHs in the past three years, back to the background composition. Results indicate low to moderate levels of PAH pollution in this region at present, which are unlikely to cause adverse effects on benthic communities. PMID- 26895566 TI - In vivo deep tissue imaging using wavefront shaping optical coherence tomography. AB - Multiple light scattering in tissue limits the penetration of optical coherence tomography (OCT) imaging. Here, we present in vivo OCT imaging of a live mouse using wavefront shaping (WS) to enhance the penetration depth. A digital micromirror device was used in a spectral-domain OCT system for complex WS of an incident beam which resulted in the optimal delivery of light energy into deep tissue. Ex vivo imaging of chicken breasts and mouse ear tissues showed enhancements in the strength of the image signals and the penetration depth, and in vivo imaging of the tail of a live mouse provided a multilayered structure inside the tissue. PMID- 26895565 TI - A phase I pharmacodynamic study of GTI-2040, an antisense oligonucleotide against ribonuclotide reductase, in acute leukemias: a California Cancer Consortium study. AB - We performed a phase I study of GTI-2040, an antisense oligonucleotide against ribonucleotide reductase mRNA, on a novel dosing schedule of days 1-4 and 15-18 by continuous infusion to examine efficacy and tolerability in patients with leukemia. A dose of 11 mg/kg/d was safely reached. Dose-limiting toxicities (DLTs) at the higher levels included elevated troponin I and liver function enzymes. There were no objective responses to GTI-2040 in this study; 7/24 patients were able to complete the predetermined three infusion cycles. Pharmacokinetic and pharmacodynamic studies were performed, indicating a trend towards increasing intracellular drug levels and decreasing RRM2 gene expression with increasing doses. This dose schedule may be considered if appropriate combinations are identified in preclinical studies. PMID- 26895567 TI - Treating Benign Paroxysmal Positional Vertigo in the Patient With Traumatic Brain Injury: Effectiveness of the Canalith Repositioning Procedure. AB - OBJECTIVE: The aim of this study was to determine the effectiveness of the canalith repositioning procedure (CRP) in the treatment of benign paroxysmal positional vertigo (BPPV) among patients after mild-to-moderate traumatic brain injury. METHODS: An unblinded, nonrandomized, case comparison interventional study with repeated measures (1, 5, 9, and 12 weeks postenrollment) of three groups of patients with traumatic brain injury (BPPV, n = 21; nonspecific dizziness, n = 23; no dizziness, n = 12) was conducted. Patients in the BPPV group received the CRP at baseline and repeatedly until a negative Dix-Hallpike Maneuver was observed. Participants in the other two groups did not receive the CRP. RESULTS: Symptom resolution at the 12-week follow-up was observed in 75% of patients in the BPPV group versus 8.3% in the nonspecific dizziness group (p = .0006). A significant Group * Time interaction was observed for the Dizziness Handicap Inventory (F = 4.2, p = .003) and 36-item Short Form Health Questionnaire physical component scores (F = 2.16, p = .035) with the BPPV group showing significantly improved scores by the 12-week follow-up. Although there were between-group differences on the 36-item Short Form Health Questionnaire mental health component scores (F = 4.06, p = .022), changes over time were not significant in the groups. CONCLUSIONS: Treatment with the CRP for posttraumatic BPPV resulted in significant symptom resolution and improvement in perceived physical health status. PMID- 26895562 TI - Optimizing Virus Identification in Critically Ill Children Suspected of Having an Acute Severe Viral Infection. AB - OBJECTIVES: Multiplex rapid viral tests and nasopharyngeal flocked swabs are increasingly used for viral testing in PICUs. This study aimed at evaluating how the sampling site and the type of diagnostic test influence test results in children with suspected severe viral infection. DESIGN: Prospective cohort study. SETTING: PICUs at 21 tertiary pediatric referral centers in the United States. PATIENTS: During the 2010-2011 and 2011-2012 influenza seasons, we enrolled children (6 mo to 17 yr old) who were suspected to have severe viral infection. INTERVENTIONS: We collected samples by using a standardized protocol for nasopharyngeal aspirate and nasopharyngeal flocked swabs in nonintubated patients and for endotracheal tube aspirate and nasopharyngeal flocked swabs in intubated patients. MEASUREMENTS AND MAIN RESULTS: Viral testing included a single reverse transcription-polymerase chain reaction influenza test and the GenMark Respiratory Viral Panel (20 viruses). We enrolled 90 endotracheally intubated and 133 nonintubated children. We identified influenza in 45 patients with reverse transcription-polymerase chain reaction testing; the multiplex panel was falsely negative for influenza in two patients (4.4%). Six patients (13.3%) had not been diagnosed with influenza in the PICU. Non-influenza viruses were identified in 172 of 223 children (77.1%). In nonintubated children, the same virus was identified by nasopharyngeal flocked swabs and nasopharyngeal aspirate in 133 of 183 paired samples (72.7%), with +nasopharyngeal aspirate/-nasopharyngeal flocked swabs in 32 of 183 paired samples (17.4%). In intubated children, the same virus was identified by nasopharyngeal flocked swabs and endotracheal tube aspirate in 67 of 94 paired samples (71.3%), with +nasopharyngeal flocked swabs/- endotracheal tube aspirate in 22 of 94 paired samples (23.4%). Most discrepancies were either adenovirus or rhinovirus in both groups. CONCLUSIONS: Standardized specimen collection and sensitive diagnostic testing with a reverse transcription polymerase chain reaction increased the identification of influenza in critically ill children. For most pathogenic viruses identified, results from nasopharyngeal flocked swabs agreed with those from nasopharyngeal or endotracheal aspirates. PMID- 26895568 TI - Where Does the Time Go? The Effect of Protocols for Stroke Last Known Well Documentation on Intravenous Recombinant Tissue Plasminogen Activator Delivery in the Northeast. AB - BACKGROUND: Despite significant efforts to improve thrombolytic use in the United States, only a small number of patients with ischemic stroke are currently treated. Although there are a number of contraindications to tissue plasminogen activator use, many patients are excluded because of the narrow therapeutic time window, which is determined by the "last known well" (LKW) time. However, it is unclear how the LKW is obtained and documented in the acute hospital setting. METHODS: We surveyed hospitals throughout the Northeast region to determine if they had established protocols for documenting LKW times. Treatment rates as reported to Get with The Guidelines Stroke were then compared in hospitals with and without established protocols for documenting LKW times. RESULTS: The majority of hospitals (73%) lacked established protocols for LKW documentation. Those without established protocols more often missed this variable when reporting to Get With The Guidelines-Stroke. Treatment rates were low overall (7%), although rates in patients who presented within 2 hours of symptom onset were high in hospitals whether they had an established protocol (86%) or not (87%). However, the lack of documentation of LKW is common and could influence the treatment rates if patients are erroneously excluded from treatment. CONCLUSIONS: Improved documentation of LKW times should be attempted. The addition of this variable to existing protocols could more accurately track the number of patients ineligible for treatment based on delayed presentation. PMID- 26895569 TI - Nursing Bedside Dysphagia Screen: Is it Valid? AB - Screening for dysphagia on stroke patient admissions in a timely manner, with early risk identification, and implementation of appropriate oral intake measures is a priority to reduce negative patient outcomes. Containing patient and facility costs, along with reducing length of stay, is a priority for all healthcare institutions. To ensure the provision of care at our facility was consistent with these priorities, we reviewed our processes and looked for opportunities for improvement. Assuring we had a reliable and valid nursing bedside screening tool for dysphagia was identified as a priority. We designed a study to answer the questions of validity and reliability. The findings suggest that our facility-developed Nursing Bedside Dysphagia Screen is a valid and reliable tool to help identify patients with stroke who are at risk for aspiration pneumonia. PMID- 26895571 TI - Calibrated complex impedance of CHO cells and E. coli bacteria at GHz frequencies using scanning microwave microscopy. AB - The application of scanning microwave microscopy (SMM) to extract calibrated electrical properties of cells and bacteria in air is presented. From the S 11 images, after calibration, complex impedance and admittance images of Chinese hamster ovary cells and E. coli bacteria deposited on a silicon substrate have been obtained. The broadband capabilities of SMM have been used to characterize the bio-samples between 2 GHz and 20 GHz. The resulting calibrated cell and bacteria admittance at 19 GHz were Y cell = 185 MUS + j285 MUS and Y bacteria = 3 MUS + j20 MUS, respectively. A combined circuitry-3D finite element method EMPro model has been developed and used to investigate the frequency response of the complex impedance and admittance of the SMM setup. Based on a proposed parallel resistance-capacitance model, the equivalent conductance and parallel capacitance of the cells and bacteria were obtained from the SMM images. The influence of humidity and frequency on the cell conductance was experimentally studied. To compare the cell conductance with bulk water properties, we measured the imaginary part of the bulk water loss with a dielectric probe kit in the same frequency range resulting in a high level of agreement. PMID- 26895570 TI - Causes of Secondary Radial Nerve Palsy and Results of Treatment. AB - BACKGROUND The aim of this study was to analyze the causes that lead to secondary damage of the radial nerve and to discuss the results of reconstructive treatment. MATERIAL AND METHODS The study group consisted of 33 patients treated for radial nerve palsy after humeral fractures. Patients were diagnosed based on clinical examinations, ultrasonography, electromyography, or nerve conduction velocity. During each operation, the location and type of nerve damage were analyzed. During the reconstructive treatment, neurolysis, direct neurorrhaphy, or reconstruction with a sural nerve graft was used. The outcomes were evaluated using the Medical Research Council (MRC) scales and the quick DASH score. RESULTS Secondary radial nerve palsy occurs after open reduction and internal fixation (ORIF) by plate, as well as by closed reduction and internal fixation (CRIF) by nail. In the case of ORIF, it most often occurs when the lateral approach is used, as in the case of CRIF with an insertion interlocking screws. The results of the surgical treatment were statistically significant and depended on the time between nerve injury and revision (reconstruction) surgery, type of damage to the radial nerve, surgery treatment, and type of fixation. Treatment results were not statistically significant, depending on the type of fracture or location of the nerve injury. CONCLUSIONS The potential risk of radial nerve neurotmesis justifies an operative intervention to treat neurological complications after a humeral fracture. Adequate surgical treatment in many of these cases allows for functional recovery of the radial nerve. PMID- 26895572 TI - Vancomycin toxicity in neonates: a review of the evidence. AB - PURPOSE OF REVIEW: Vancomycin is a first-line agent in the treatment of serious Gram-positive infections in the neonatal population. The published evidence on vancomycin toxicity in neonates is limited. This review summarizes preclinical studies and clinical trials describing vancomycin toxicity. We discuss proposed pathophysiology and summarize evidence supporting dose-response relationships, genetic and environmental determinants, and consider future research required to further define vancomycin toxicity. RECENT FINDINGS: Current dosing regimens for vancomycin result in subtherapeutic levels in a large proportion of patients. Higher daily doses have been proposed, which have led to concerns regarding increased toxicity. Nephrotoxicity occurs in 1-9% of neonates receiving currently recommended doses. The incidence is highest in those receiving concomitant nephrotoxic drugs. Vancomycin-associated ototoxicity is rare in patients of all ages. Exposure-toxicity relationships in relation to nephrotoxicity and ototoxicity have not been clearly defined in neonates receiving vancomycin. SUMMARY: Current evidence supports the favourable safety profile of vancomycin in neonates. Further studies that address safety concerns relating to high-dose intermittent dosing regimens are needed. Such studies must include robust and standardized definitions of renal and hearing impairment, and include follow-up of sufficient length to establish the long-term implications of experimental findings. PMID- 26895574 TI - Trends in thyroid cancer incidence and mortality in Portugal. AB - The objective was to quantify thyroid cancer incidence and mortality trends in Portugal. The number of thyroid cancer cases and incidence rates were retrieved from the Regional Cancer Registries for the period 1989-2011. The number of deaths and mortality rates were obtained from the WHO cancer mortality database (1988-2003 and 2007-2012) and Statistics Portugal (2004-2006; 1988-2012 by region). Joinpoint regression of the standardized incidence and mortality rates was performed. A significant, rapid and continued increase in incidence was observed for both sexes in each of the Regional Cancer Registries, with annual per cent changes (APCs) ranging between 2 and 9. Incidence in Portuguese women is higher than estimates for the world and Europe. Mortality decreased for women (APC: -1.5), with the greatest decrease in the North, and increased marginally for men (APC: +0.2), with a greater increase in the South. The significant increases in incidence in Portugal are predominantly because of the increase in incidence among women from the North. These trends, combined with an overall low mortality and high 5-year relative survival, raise concerns on the extent to which overdiagnosis may be taking place. Further research is needed, quantifying the importance of the most likely determinants of these trends as well as the extent and potentially deleterious effects of overdiagnosis and overtreatment in the Portuguese setting. PMID- 26895575 TI - Cervical cancer screening among homeless women in the Greater Paris Area (France): results of the ENFAMS survey. AB - Little is known about the prevalence of cervical cancer screening (CCS) and its correlates among homeless women in France. The objectives of this study were to determine the prevalence of women who had never been screened for cervical cancer and to identify the associated factors. This cross-sectional study was based on data collected in the ENFAMS survey, which was conducted in 2013 among 764 sheltered homeless mothers in the Greater Paris Area. Robust Poisson regression models were used to estimate the association between no lifetime CCS and certain sociodemographic and health-related factors (selected from the behavioral model of vulnerable populations). Analyses were carried out separately for women with and without a regular gynaecological follow-up (RGF). The proportion of never screeners was 33% among the women with an RGF versus 64% among those without an RGF (P<0.001). Among the latter, never having been screened for CCS was associated mainly with socioeconomic conditions, the length of time lived in France, a history of delivery in France and the duration of homelessness. In those with an RGF, the factors were mainly poor health service utilization and language difficulties. This first quantitative study of CCS among homeless women in the Greater Paris Area points to the need for it to be proposed and performed more systematically in primary care. Every contact between this hard-to-reach population and health services should be an opportunity to check their screening status and to ensure that those in need actually undergo a Pap test. PMID- 26895573 TI - Tissue tropisms in group A Streptococcus: what virulence factors distinguish pharyngitis from impetigo strains? AB - PURPOSE OF REVIEW: Group A streptococci (GAS) are a common cause of pharyngitis and impetigo, and distinct throat strains and skin strains have been long recognized. This review aims to describe recent advances in molecular differences between throat and skin strains, and the pathogenic mechanisms used by virulence factors that may distinguish between these two groups. RECENT FINDINGS: Recent findings include a new typing scheme for GAS strains based on sequence clusters of genes encoding the entire surface-exposed portion of M protein; correlations between emm-based typing schemes, clinical disease and surface adhesins; covalent bond formation mediated by GAS pili and other adhesins in binding to host ligands; a key role for superantigens in oropharyngeal infection via binding major histocompatibility complex class II antigen; and migration of GAS-specific Th17 cells from the upper respiratory tract to the brain, which may be relevant to autoimmune sequelae. SUMMARY: The gap between molecular markers of disease (correlation) and virulence mechanisms (causation) in the establishment of tissue tropisms for GAS infection currently remains wide, but the gap also continues to narrow. Whole genome sequencing combined with mutant construction and improvements in animal models for oropharyngeal infection by GAS may help pave the way for new discoveries. PMID- 26895576 TI - Factors Affecting the Conclusion of Association between Funding and Findings in Plastic Surgery. PMID- 26895577 TI - Mark Gorney, M.D., 1924 to 2014. PMID- 26895578 TI - Surgical Simulator Training for Plastic Surgery Residents around the World. PMID- 26895579 TI - How Do You Know When It Is Time to Retire? PMID- 26895580 TI - Effect of Cooling on Free Flap Ischemia. PMID- 26895581 TI - Reply: Financial Conflicts of Interest: An Association between Funding and Findings in Plastic Surgery. PMID- 26895582 TI - Evolving Concepts of Keystone Perforator Island Flaps (KPIF): Principles of Perforator Anatomy, Design Modifications, and Extended Clinical Applications. AB - BACKGROUND: Keystone flaps have demonstrated growing clinical applications in reconstructive surgery in the past decade. This article highlights flap modifications and their versatility for clinical applications and management of complex defects. METHODS: A retrospective chart review was conducted of consecutive patients undergoing keystone flap reconstruction at the authors' institution from January of 2012 to December of 2014. Patient demographics, indications, and operative and postoperative details were abstracted. RESULTS: Forty-two keystone flaps were performed in 36 patients. Indications included malignant melanoma (n = 14), soft-tissue sarcoma (n = 12), benign pathologic conditions (e.g., exposed hardware, enterocutaneous fistula, tissue necrosis) (n = 6), and nonmelanoma skin cancer (n = 4). Twenty-eight percent received neoadjuvant irradiation, and 70 percent of these were for sarcoma. Locoregional adjunct flaps were performed in eight patients. The deep fascia was nearly completely in a circumferential manner in 18 of 36 patients (50 percent), in 92 percent of the sarcoma reconstructions, and located mainly in the lower extremity. Average defect size was 215 cm (range, 4 to 1000 cm). Average defect size was 474 cm and 35.8 cm after sarcoma and malignant melanoma resection, respectively. Average flap size was 344 cm (range, 5 to 1350 cm). Ninety percent of cases had flap sizes exceeding the traditional 1:1 ratio. There was no flap loss or partial necrosis. Mean time to mobilization was 1.8 days, and mean hospital length of stay was 6.8 days. CONCLUSIONS: Keystone flaps offer an excellent versatile tool for reconstructive surgeons. Fundamental principles behind the vascular basis of the keystone flap and its modifications permit their greater utility in complex wounds in the settings of large oncologic resections, irradiation, and trauma. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV. PMID- 26895583 TI - Analysis of References on the Plastic Surgery In-Service Training Exam. AB - BACKGROUND: The Plastic Surgery In-Service Training Exam is a knowledge assessment tool widely used during plastic surgery training in the United States. This study analyzed literature supporting correct answer choices to determine highest yield sources, journal publication lag, and journal impact factors. METHODS: Digital syllabi of 10 consecutive Plastic Surgery In-Service Training Exam administrations (2006 to 2015) were reviewed. The most-referenced articles, journals, and textbooks were determined. Mean journal impact factor and publication lag were calculated and differences were elucidated by section. RESULTS: Two thousand questions and 5386 references were analyzed. From 2006 to 2015, the percentage of journal citations increased, whereas textbook references decreased (p < 0.001). Plastic and Reconstructive Surgery was cited with greatest frequency (38.5 percent), followed by Clinics in Plastic Surgery (5.6 percent), Journal of Hand Surgery (American volume) (5.1 percent), and Annals of Plastic Surgery (3.8 percent). There was a trend toward less publication lag over the study period (p = 0.05), with a mean publication lag of 9.1 +/- 9.0 years for all journal articles. Mean journal impact factor was 2.3 +/- 4.3 and lowest for the hand and lower extremity section (1.7 +/- 2.8; p < 0.001). The highest yield textbooks were elucidated by section. CONCLUSION: Plastic surgery faculty and residents may use these data to facilitate knowledge acquisition during residency. PMID- 26895584 TI - Management of the Formosa Color Dust Explosion: Lessons Learned from the Treatment of 49 Mass Burn Casualty Patients at Chang Gung Memorial Hospital. AB - BACKGROUND: This article reports the emergency management of a mass casualty disaster occurring on June 27, 2015, in New Taipei, Taiwan, as a fire erupted over a large crowd, injuring 499 people. Lessons learned in burn care treatment and disaster preparedness are analyzed through following the specific surgical response and patient outcomes of one hospital involved in the disaster response. METHODS: Information regarding the fire and emergency management was obtained from the Ministry of Health and Welfare of Taiwan. Patient-specific data were obtained from Chang Gung Memorial Hospital's patient records. RESULTS: A mass casualty management system was immediately initiated by the Ministry of Health and Welfare, which contacted local hospitals to prepare for the influx of patients with severe burn injuries. In response, Chang Gung Memorial Hospital called 336 medical personnel to the emergency room for the management of 49 burn patients and divided emergency management roles among chief physicians. The mean burn total body surface area of patients presenting to this hospital was 44.2 percent (range, 10 to 90 percent). No deaths occurred in the first 48 hours after the explosion. As of 3 months after the incident, only 12 deaths had resulted from this accident, all resulting from sepsis and organ failure. CONCLUSIONS: Taiwan's effective mass casualty preparation plans, highly trained medical personnel, and large centers capable of treating burn patients allowed 499 injured patients to be successfully transferred and treated in hospitals across Taiwan. Lessons learned from this disaster response can be integrated into existing disaster management plans to aid in the response to mass casualty tragedies. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV. PMID- 26895585 TI - Low Levels of Evidence on the Plastic Surgery In-Service Training Exam. AB - BACKGROUND: The Plastic Surgery In-Service Training Exam is written by the American Society of Plastic Surgeons. Examinees reasonably infer that tested material reflects the Society's vision for the core curriculum in plastic surgery. The purpose of this study was to determine the levels of evidence on which credited answers to the examination questions are based. METHODS: Two recent Plastic Surgery In-Service Training Exams (2014 and 2015) were analyzed. Questions were categorized using a taxonomy model. Recommended journal article references for Level III (decision-making) questions were assigned a level of evidence. Exam sections were analyzed for differences in question taxonomy distribution and level of evidence. To look for studies with higher levels of evidence, a PubMed search was conducted for a random sample of 10 questions from each section. RESULTS: One hundred three Level I (25.8 percent), 138 Level II (34.5 percent), and 159 Level III (39.8 percent) questions were analyzed (p < 0.001). The hand and lower extremity section had the highest percentage of Level III questions (50.0 percent; p = 0.005). Journal articles had a mean level of evidence of 3.9 +/- 0.7. The number of articles with a low level of evidence (IV and V) (p = 0.624) and the percentage of questions supported by articles with a high level of evidence (I and II) (p = 0.406) did not vary by section. The PubMed search revealed no instances of a higher level of evidence than the recommended reading list. CONCLUSIONS: A significant percentage of Plastic Surgery In-Service Training Exam questions test clinical management, but most are supported with a low level of evidence. Although that is consistent with low level of evidence of plastic surgery literature, educators should recognize the potential for biases of question writers. PMID- 26895586 TI - Platelet-Rich Plasma with Basic Fibroblast Growth Factor for Treatment of Wrinkles and Depressed Areas of the Skin. PMID- 26895587 TI - Reply: Platelet-Rich Plasma with Basic Fibroblast Growth Factor for Treatment of Wrinkles and Depressed Areas of the Skin. PMID- 26895588 TI - Limited Panniculectomy for Adult Buried Penis Repair. PMID- 26895589 TI - A Novel Technique for Seal Augmentation in Negative-Pressure Wound Therapy. PMID- 26895591 TI - Reply: Comparison of Outcomes for Normal Saline and an Antiseptic Solution for Negative-Pressure Wound Therapy with Instillation. PMID- 26895590 TI - Reply: Comparison of Outcomes for Normal Saline and an Antiseptic Solution for Negative-Pressure Wound Therapy with Instillation. PMID- 26895592 TI - Reply: Limited Panniculectomy for Adult Buried Penis Repair. PMID- 26895593 TI - Assessment of natural radioactivity and (137)Cs in some coastal areas of the Saudi Arabian gulf. AB - The levels of natural radioactivity have been investigated in some Saudi Arabian Gulf coastal areas. Sampling sites were chosen according to the presence of nearby non-nuclear industrial activities such as, the two main water desalination plants in Al Khobar and Al Jubail, and Maaden phosphate complex in Ras Al Khair, to ensure that effluents discharges into the Arabian Gulf didn't enhance radioactivity in seawater and shore sediments. Seawater samples were analyzed for radium isotopes (Ra-226 & Ra-228) and measured by gamma spectrometry using high purity germanium detector, after radiochemical separation of the isotopes by co precipitation with MnO2. Shore sediment samples were analyzed for (226)Ra, (228)Ra ((232)Th), (4) degrees K and (137)Cs using gamma sepectrometry. A small variation was observed in the activity concentrations of the investigated radioisotopes, and the activity levels were comparable to those reported in literature. Quality assurance and methods validation were established through the efficiency calibration of the detectors, the estimation of uncertainties, the use of blanks, the analysis of standard reference materials and the intercomparison and proficiency tests. Radiological hazards were assessed, and the annual effective dose had an average value of 0.02 mSv. On the basis of the current results, we may conclude that any radiological hazards to the public visiting these shores are not expected. PMID- 26895594 TI - Polychlorinated biphenyls and organochlorine pesticides as intrinsic tracer tags of foraging grounds of bluefin tuna in the northwest Atlantic Ocean. AB - Researchers have utilized chemical fingerprints in the determination of habitat utilization and movements of the aquatic animals. In the present effort, we analyzed polychlorinated biphenyl (PCB) congeners and organochlorine pesticides in the samples of juvenile bluefin tuna caught offshore of Virginia, and in larger bluefin tuna from the Gulf of Maine and near Nova Scotia. For a given specimen, or a given location, PCB concentrations were highest, followed by DDTs, and chlordanes. Average contaminant concentrations from fish captured from the three locations were not significantly different; and PCBs, DDTs, and chlordanes correlated well with each other. Trans-nonachlor/PCB 153 ratios in bluefin tuna of eastern Atlantic (i.e., Mediterranean) origin are low compared to the corresponding ratios in fish in the western Atlantic. As the former migrate to the western Atlantic, these ratios gradually turnover due to the accumulation of biomass from forage contaminated with higher trans-nonachlor/PCB 153 ratio reflecting dissimilar use of chlordane pesticides on two sides of the Atlantic Ocean. The trans-nonachlor/PCB 153 ratio indicated that one juvenile bluefin tuna from offshore of Virginia and one large bluefin tuna from Gulf of Maine in the present study originated from foraging grounds in the Mediterranean Sea, and that they have made the trans-Atlantic migrations. The remaining individuals were determined to be either spawned in the Gulf of Mexico or the trans-nonachlor/PCB 153 ratio for the putative Mediterranean bluefin tuna was completely turned over to resemble the ratio characteristic to the western Atlantic. Based on the turnover time for trans-nonachlor/PCB 153 ratio previously determined, the residence time of juvenile bluefin tuna offshore Virginia was estimated to be at least 0.8 to 1.6years. A discriminant function analysis (DFA) plot of total PCB normalized signatures of PCB congeners showed three separate clusters, which suggested that bluefin tuna from offshore Virginia, Gulf of Maine, and Nova Scotia could have had extended residences and foraging within the areas of capture to be able to sustain the stable signatures of PCB congeners. The DFA cluster results supported the concept of metapopulation theory of spatial ecology comprising discrete aggregates of local populations of bluefin tuna where the desired prey species are likely to be abundant. Despite their highly migratory trait and endothermic advantage of foraging in broader and colder habitats, the movements and mixing across the aggregation ranges related to feeding did not appear to be extensive. Advancement in the understanding of bluefin tuna population dynamics beyond the coarse concept of trans-Atlantic migrations to the metapopulation hypothesis provides a novel exploratory tool in the stock assessment and resource management. As the chemical tracer tags are fortified naturally and document the time- and space-integrated foraging history, they promise to serve as the low-cost alternatives to the high-cost electronic data recording tags employed for addressing the migratory movements of bluefin tuna. Between the different potential chemical tracer tags, a distinct advantage of PCB/pesticide analysis over the otolith micro-constituent analysis is that the muscle tissue of a given individual bluefin tuna can be sampled repeatedly for PCB/pesticide analysis over different spatial and temporal scales in a non-lethal manner. PMID- 26895595 TI - Selective responses of benthic foraminifera to thermal pollution. AB - Persistent thermohaline pollution at a site along the northern coast of Israel, due to power and desalination plants, is used as a natural laboratory to evaluate the effects of rising temperature and salinity levels on benthic foraminifera living in shallow hard-bottom habitats. Biomonitoring of the disturbed area and a control station shows that elevated temperature is a more significant stressor compared to salinity, thus causing a decrease in abundance and richness. Critical temperature thresholds were observed at 30 and 35 degrees C, the latter representing the most thermally tolerant species in the studied area Pararotalia calcariformata, which is the only symbiont-bearing species observed within the core of the heated area. Common species of the shallow hard-bottom habitats including several Lessepsian invaders are almost absent in the most exposed site indicating that excess warming will likely impede the survival of these species that currently benefit from the ongoing warming of the Eastern Mediterranean. PMID- 26895596 TI - Combined environmental stress from shrimp farm and dredging releases in a subtropical coastal lagoon (SE Gulf of California). AB - Nutrient pollution causes environmental damages on aquatic ecosystems worldwide. Eutrophication produces impacts in coastal ecosystems, affecting biota and ecosystem services. The Urias coastal lagoon (SE Gulf of California) is a sub tropical estuary under several environmental pressures such as nutrient inputs from shrimp farm effluents and dredging related to port operations, which can release substances accumulated in sediments. We assessed the water quality impacts caused by these activities and results showed that i) nitrogen was the limiting nutrient, ii) shrimp farm effluents increased particulate organic matter and chlorophyll a in the receiving stations, and iii) dredging activities increased nitrite and reduced dissolved oxygen concentrations. The co-occurrence of the shrimp farm releases and dredging activities was likely the cause of a negative synergistic effect on water quality which mainly decreases dissolved oxygen and increases nitrite concentrations. Coastal zone management should avoid the co-occurrence of these, and likely others, stressors in coastal ecosystems. PMID- 26895597 TI - Inferior angle of scapula fractures: a review of literature and evidence-based treatment guidelines. AB - BACKGROUND: Inferior angle of scapula (IAS) fractures are rare, with very few cases reported. They typically present with pain, loss of shoulder motion, and scapula winging. Operative and nonoperative treatments have been trialed with varying success. The aim of this study was to gather data relating to IAS fractures to develop evidence-based treatment guidelines as none are currently available. METHODS: A search was conducted of the PubMed and Google Scholar databases to identify cases of IAS fractures. Data collected about each case included age and gender of the patient, mechanism of injury, fracture displacement, treatment, and outcome. The authors report 2 additional IAS fracture cases. RESULTS: Ten cases were identified for inclusion in this study, 8 from the literature and 2 described by the authors. Of the 10 cases, 7 described displaced IAS fractures and 3 described undisplaced fractures. All displaced fractures treated nonoperatively resulted in a painful nonunion. All that underwent operative fixation, whether acutely or after failed nonoperative treatment, had resolution of pain and a good functional outcome. All undisplaced fractures were treated nonoperatively; 1 had persisting pain. Surgical exploration identified the fracture fragment attached to serratus anterior in 2 cases and attached to both serratus anterior and latissimus dorsi in 2 cases. DISCUSSION AND CONCLUSIONS: There are limited data available about IAS factures. From the cases reviewed, treatment recommendations include the following: (1) displaced IAS fractures should undergo operative fixation to prevent the development of a painful nonunion; (2) suture repair provides adequate fixation; and (3) undisplaced fractures have a variable outcome when treated nonoperatively. PMID- 26895598 TI - The effects of prosthetic humeral head shape on glenohumeral joint kinematics during humeral axial rotation in total shoulder arthroplasty. AB - BACKGROUND: A non-spherical humeral head has been shown to influence kinematics and stability of the glenohumeral joint; yet, most prosthetic humeral head components are designed to be a perfect sphere. The effect of humeral head shape on prosthetic joint kinematics after total shoulder arthroplasty is not well understood. We hypothesized that prosthetic joint kinematics during humeral axial rotation is dependent on humeral head shape, regardless of joint conformity. METHODS: Four prosthetic configurations were investigated using a spherical and a non-spherical prosthetic humeral head articulated with a conforming and a non conforming glenoid component. Testing was performed in the coronal, scapular, and forward flexion plane at 0 degrees , 30 degrees , and 60 degrees of abduction. Prosthetic joint kinematics was measured in 10 degrees intervals during a 100 degrees arc of humeral axial rotation. Glenohumeral translation patterns, net glenohumeral translation, and averaged glenohumeral translation were compared for each of 4 configurations. RESULTS: Non-spherical head configurations increased the net glenohumeral translation during humeral axial rotation in multiple test positions compared with spherical head configurations (P < .05). Spherical head configurations resulted in a relatively small amount of glenohumeral translation, less than 2 mm. The radius of curvature of the glenoid component alone did not affect the net glenohumeral translation within each of the 2 head groups (P > .05). CONCLUSION: During humeral axial rotation, the non-spherical humeral head shape contributes to increased glenohumeral translation during humeral axial rotation. However, the spherical head shape does not show significant glenohumeral translation during humeral axial rotation, regardless of glenoid conformity. PMID- 26895599 TI - Reverse total shoulder arthroplasty in wheelchair-dependent patients. AB - BACKGROUND: Wheelchair-dependent patients have a high incidence of shoulder pathology, often causing severe impairment. This study reports outcomes of wheelchair-dependent lower extremity-impaired patients with symptomatic shoulder arthritis or severe rotator cuff pathology treated with reverse total shoulder arthroplasty (RTSA). METHODS: Data for 19 wheelchair-dependent patients who had an RTSA for symptomatic arthritis or rotator cuff pathology, or both, were obtained from the University of Florida Shoulder Arthroplasty Database. Included were 16 of 19 shoulders with adequate follow-up averaging 40 months. Functional outcome scores included the Simple Shoulder Test, University of California Los Angeles Shoulder Rating Scale, Shoulder Pain and Disability Index, American Shoulder and Elbow Surgeons score, Constant score, and 12-item Short Form (SF-12) health survey. Objective measures were active elevation, external rotation, and internal rotation. Radiographs were evaluated for lucent lines, notching, and prosthetic loosening. RESULTS: All measured parameters, except the SF-12, significantly improved at the final follow-up. Functional outcome scores included Shoulder Pain and Disability Index, 45; Simple Shoulder Test, 7; American Shoulder and Elbow Surgeons, 73; University of California Los Angeles Shoulder Rating Scale, 30; Constant, 70; and SF-12, 33. Active elevation was 112 degrees , and active external rotation was 29 degrees . Most patients (83%) were satisfied. The complication rate was 25%; baseplate failure and dislocation occurred early, and periprosthetic humeral fracture secondary to infection occurred late. The notching rate was 42%. CONCLUSIONS: Shoulder pain and dysfunction due to arthritis and rotator cuff pathology can result in the loss of independence in wheelchair-dependent patients. We investigated whether RTSA can sustain the increased loads placed by these patients during transfers. Wheelchair-dependent patients can benefit from an RTSA for shoulder pain and dysfunction but must accept worsened impairment during the immediate postoperative period and a higher complication rate than the general population treated with an RTSA. PMID- 26895600 TI - Premorbid retroversion is significantly greater in type B2 glenoids. AB - BACKGROUND: Posterior glenoid erosion is thought to be initiated by humeral head subluxation. However, it is unknown whether subluxation is entirely caused by soft-tissue instability and unbalanced muscle activity or whether osseous morphology is a contributing factor. We hypothesized that patients with posterior erosion may exhibit premorbid glenoid morphology that is inherently retroverted and inferiorly inclined compared with age-matched normal glenoids. METHODS: This study examined 80 scapulae, evenly distributed between 2 groups: osteoarthritic with type B2 glenoids and age-matched normal glenoids. From 3-dimensional computed tomography reconstructions, version and inclination were measured from the anterior paleoglenoid region of the B2 glenoids, which is representative of the premorbid glenoid, and compared with measurements obtained from similar regions in the normal cohort. RESULTS: The anterior paleoglenoid region of B2 glenoids was significantly (P < .001) more retroverted (-14 degrees +/- 6 degrees ) compared with similar regions in nonarthritic normal glenoids (-5 degrees +/- 5 degrees ). There were no significant differences (P = .166) in the glenoid inclination angle between type B2 glenoids (0 degrees +/- 6 degrees ) and nonarthritic normal glenoids (2 degrees +/- 5 degrees ). Negative values represent retroverted and inferiorly inclined glenoids. DISCUSSION: Understanding premorbid glenoid morphologic variations may provide insight into the pathoanatomy of humeral head subluxation, osteoarthritis, and posterior glenoid erosion. The results of this study indicate that patients with type B2 osteoarthritic glenoids have significantly greater premorbid glenoid retroversion compared with nonarthritic normal glenoids, suggesting that this premorbid morphologic variation may be one contributing factor to posterior erosion. PMID- 26895601 TI - Intramedullary nailing of the proximal humerus: evolution, technique, and results. AB - Proximal humerus fractures are the third most common fracture in the elderly. Although most fractures can be treated conservatively with acceptable outcomes, certain fracture patterns are at high risk for progression to humeral malunions, nonunions, stiffness, and post-traumatic arthrosis. The goal of antegrade humeral nailing of proximal humerus fractures is to provide stability to a reduced fracture that allows early motion to optimize patient outcomes. Certain technical pearls are pivotal in managing these difficult fractures with nails; these include rotator cuff management, respect of the soft tissues, anatomic tuberosity position, blood supply maintenance, knowledge of the deforming forces on the proximal humerus, fracture reduction, and rehabilitation strategies. Modern proximal humeral nail designs and techniques assist the surgeon in adhering to these principles and have demonstrated promising outcomes. Humeral nail designs have undergone significant innovation during the past 40 years and now can provide stable fixation in the humeral shaft distally as well as improved stability in the head and tuberosity fragments, which were the common site of fixation failure with earlier generation implants. Compared with other fixation strategies, such as locking plate fixation, no compelling evidence exists to suggest one technique over another. The purpose of this review is to describe the history, results, new designs, and techniques that make modern intramedullary nailing of proximal humerus fractures a viable treatment option. PMID- 26895602 TI - Dropless Cataract Surgery: What Are the Potential Downsides? PMID- 26895604 TI - Optimal dosing regimen of biapenem in Chinese patients with lower respiratory tract infections based on population pharmacokinetic/pharmacodynamic modelling and Monte Carlo simulation. AB - In this study, a population pharmacokinetic (PPK) model of biapenem in Chinese patients with lower respiratory tract infections (LRTIs) was developed and optimal dosage regimens based on Monte Carlo simulation were proposed. A total of 297 plasma samples from 124 Chinese patients were assayed chromatographically in a prospective, single-centre, open-label study, and pharmacokinetic parameters were analysed using NONMEN. Creatinine clearance (CLCr) was found to be the most significant covariate affecting drug clearance. The final PPK model was: CL (L/h)=9.89+(CLCr-66.56)*0.049; Vc (L)=13; Q (L/h)=8.74; and Vp (L)=4.09. Monte Carlo simulation indicated that for a target of >=40% T>MIC (duration that the plasma level exceeds the causative pathogen's MIC), the biapenem pharmacokinetic/pharmacodynamic (PK/PD) breakpoint was 4MUg/mL for doses of 0.3g every 6h (3-h infusion) and 1.2g (24-h continuous infusion). For a target of >=80% T>MIC, the PK/PD breakpoint was 4MUg/mL for a dose of 1.2g (24-h continuous infusion). The probability of target attainment (PTA) could not achieve >=90% at the usual biapenem dosage regimen (0.3g every 12h, 0.5-h infusion) when the MIC of the pathogenic bacteria was 4MUg/mL, which most likely resulted in unsatisfactory clinical outcomes in Chinese patients with LRTIs. Higher doses and longer infusion time would be appropriate for empirical therapy. When the patient's symptoms indicated a strong suspicion of Pseudomonas aeruginosa or Acinetobacter baumannii infection, it may be more appropriate for combination therapy with other antibacterial agents. PMID- 26895603 TI - Drinking Behavior and Mental Illness Among Evacuees in Fukushima Following the Great East Japan Earthquake: The Fukushima Health Management Survey. AB - BACKGROUND: Recent evidence from alcohol and trauma studies suggests that disasters are associated with increases in the consumption of alcohol. The Great East Japan Earthquake and the associated nuclear disaster have continued to affect the mental health of evacuees from Fukushima. This study aimed to extend these findings by examining the relationship between drinking behaviors and the risk of mental illness after the compound disaster. METHODS: We conducted the Mental Health and Lifestyle Survey with 56,543 evacuees. Kessler's K6 was used to assess the risk of mental illness, and logistic regression models were applied to analyze how drinking behavior patterns influence the risk of serious mental illness after adjustment for confounding variables. RESULTS: Logistic regression analysis evidenced that beginning heavy and light drinkers had the highest and a higher risk of serious mental illness, respectively. Individuals who were nondrinkers pre- and postdisaster had the lowest proportional risk of mental illness. Abstainers also had some risk to their mental health after the compound disaster. CONCLUSIONS: The results of this study highlight that beginning drinkers have a high risk of serious mental illness. Thus, mental health professionals should pay attention to the drinking behaviors of evacuees, which might predict increased risk of serious mental illness and consequently indicate a need for psychological intervention. PMID- 26895606 TI - Antibiotic administration and the development of obesity in children. AB - Antibiotics are the most common prescription drugs administered at the paediatric age, however their administration can cause unwanted problems. Among these issues, antibiotic-induced gut microbiota dysbiosis has appeared as an emerging issue and has been associated with obesity. This problem is particularly relevant in children because they are frequently treated with antibiotics. Early development of obesity increases the risk of adult obesity, which is associated with the emergence of very severe clinical problems. Dysbiosis induced in the first periods of life can have the most relevant practical consequences because a decrease in the number of microbes and their substitution with other microbes dramatically modifies the development of the immune system as well as glucose and lipid metabolism. Unfortunately, not all of the mechanisms that could explain the relationship between gut microbiota modification and the development of obesity have been defined. Consequently, no definitive therapeutic approach has been elucidated. Probiotics and prebiotics could play a role in treating microbial dysbiosis because the addition of specific bacterial strains has been associated with normal weight and has been demonstrated to be useful in clinical conditions other than obesity that are caused by microbiota disruption. Considering that antibiotics are commonly prescribed and that obesity is increasing in paediatric patients, further studies specifically designed to evaluate how to disrupt the relationship between antibiotics and dysbiosis are urgently needed. Presently, paediatricians have to consider dysbiosis to be a new and serious reason for the judicious use of antibiotics in clinical practice. PMID- 26895605 TI - Repurposing auranofin for the treatment of cutaneous staphylococcal infections. AB - The scourge of multidrug-resistant bacterial infections necessitates the urgent development of novel antimicrobials to address this public health challenge. Drug repurposing is a proven strategy to discover new antimicrobial agents; given that these agents have undergone extensive toxicological and pharmacological analysis, repurposing is an effective method to reduce the time, cost and risk associated with traditional antibiotic innovation. In this study, the in vitro and in vivo antibacterial activities of an antirheumatic drug, auranofin, was investigated against multidrug-resistant Staphylococcus aureus. The results indicated that auranofin possesses potent antibacterial activity against all tested strains of S. aureus, including meticillin-resistant S. aureus (MRSA), vancomycin intermediate S. aureus (VISA) and vancomycin-resistant S. aureus (VRSA), with minimum inhibitory concentrations (MICs) ranging from 0.0625MUg/mL to 0.125MUg/mL. In vivo, topical auranofin proved superior to conventional antimicrobials, including fusidic acid and mupirocin, in reducing the mean bacterial load in infected wounds in a murine model of MRSA skin infection. In addition to reducing the bacterial load, topical treatment of auranofin greatly reduced the production of inflammatory cytokines, including tumour necrosis factor-alpha (TNFalpha), interleukin-6 (IL-6), interleukin-1 beta (IL-1beta) and monocyte chemoattractant protein-1 (MCP-1), in infected skin lesions. Moreover, auranofin significantly disrupted established in vitro biofilms of S. aureus and Staphylococcus epidermidis, more so than the traditional antimicrobials linezolid and vancomycin. Taken together, these results support that auranofin has potential to be repurposed as a topical antimicrobial agent for the treatment of staphylococcal skin and wound infections. PMID- 26895607 TI - Reply to: Re: The challenge of Clostridium difficile infection: overview of clinical manifestations, diagnostic tools and therapeutic options. PMID- 26895608 TI - I play doh: The art of plasticine in the process of adolescent subjectivation. AB - Pre-adolescents' difficulty in portraying and communicating the internal turmoil to which puberty subjects them, both through the immaturity of their psychic functions and through the conflict between display and secrecy, presents a constant challenge to the analyst. A technical solution for making the process of subjectivation more pleasant may be found in modelling with Play Doh, a game/non game which is not age-specific, an expressive form capable of evoking in the analytic field fantasies and representations that are otherwise only accessible with difficulty. This paper aims to present some reflections on the characteristic features of the Play Doh game in the session, with particular regard to work with patients between 10 and 14 years old who are in the midst of the process of adolescent subjectivation. The paper examines the clinical history of a young adopted boy who was able to develop the ability to dream his own experience and to portray internal experiences which had previously been unrepresentable. PMID- 26895609 TI - Continence and quality of life with the modified Heitz-Boyer-Hovelacque rectal bladder for children with urinary incontinence following bladder exstrophy. AB - BACKGROUND: Bladder exstrophy and epispadias are severe congenital anomalies associated with an open bladder and urinary sphincter. Despite modern reconstruction, there is a significant incidence of residual or recurrent urinary incontinence that impacts on quality of life (QoL) and self-esteem, which in turn limits social interaction (Figure). The present study involved 14 patients, mainly from a Middle Eastern country, and reported the early findings with a modification of the Heitz-Boyer-Hovelacque rectal bladder technique for both urinary and faecal control. STUDY DESIGN: Fourteen children, with a median age of 8.1 years, with poor quality of life and low self-esteem because of urinary incontinence and small polypoidal open bladders of 5-15 ml volume, mostly after bladder exstrophy surgery, were managed with a modification of the Heitz-Boyer Hovelacque rectal bladder technique keeping an intact anal sphincter. The retrorectal pulled-through colon was anastomosed to the posterior wall of the rectum just above the external sphincter complex, thereby avoiding any possible injury to the anal sphincter. All patients had a normal colon and a competent anal sphincter without lumbosacral spinal or nerve anomalies. RESULTS: Ten children had a 5- to 10-year follow-up, one child had a 15-year follow-up, and three others, that were also continent, were excluded because of a <5-year follow up. There were no postoperative complications, and all were dry and odour-free by day within 2-4 weeks of surgery. Two children still had minor urinary loss at night. There were no UTIs and renal function remained unimpaired. Eleven years after surgery, one child underwent excision of a pedunculated benign inflammatory polyp from the tip of the left ureter because of recurrent torsion and bleeding, there was no recurrence at the 2-year follow-up. None of the rectal or ureteric biopsies from any of the children showed metaplasia or neoplasia; however, in view of the potential long-term risks, all children were placed on a lifelong 'proctoscopy and biopsy' protocol. DISCUSSION: The ability to be dry and odour free, and to wear normal clothing had a striking impact on QoL and psychological well-being of the children and their families. This was reflected in their positive overall approach, voluntary school attendance, and enthusiastic participation in communal events. All agreed that their improved genital appearance markedly contributed to their better body image and increased self esteem. CONCLUSION: These significant benefits, at a crucial time in the child's life, outweigh the potential risk of long-term neoplasia. Therefore, the Heitz Boyer-Hovelacque rectal bladder technique is recommended with long-term proctoscopic follow-up. PMID- 26895610 TI - Ocular blood flow in glaucoma - the Leuven Eye Study. AB - PURPOSE: Elevated intra-ocular pressure (IOP) has been identified as a major risk factor for glaucoma. Additionally, extensive literature depicts a vascular dysfunction to exist in these patients. However, a large ocular blood flow oriented trial to integrate these findings in the clinical setting is lacking. This study would likely help to identify which of these vascular data can be used as a clinical tool for screening and disease stratification. METHOD: Prospective, cross-sectional, case-control hospital-based study. Patients with primary open angle glaucoma (POAG), normal-tension glaucoma (NTG), ocular hypertension (OHT), glaucoma suspects and healthy volunteers were recruited. In addition to a comprehensive ophthalmological examination, a vascular-oriented questionnaire was completed and ocular blood flow assessment (colour Doppler imaging of retrobulbar vessels, retinal oximetry, dynamic contour tonometry, optical coherent tomography enhanced-depth imaging of the choroid) were performed. Statistical analysis was based on multiple imputation to account for missingness. RESULTS: A total of 614 subjects (291 males) were recruited between March and December 2013 (POAG: 214, NTG: 192; OHT: 27; glaucoma suspect: 41; healthy controls: 140). Glaucoma groups (NTG and POAG) were age and gender matched with the control group (p > 0.05). Glaucoma groups were paired in terms of functional and structural parameters (p > 0.08). Mean ocular perfusion pressure was higher in the glaucoma groups than in controls (p < 0.001). Glaucoma groups had lower retrobulbar velocities, higher retinal venous saturation and choroidal thickness asymmetries when compared to the healthy group, in line with the current literature. CONCLUSIONS: The Leuven Eye Study stands as one of the largest clinical trials on ocular blood flow in glaucoma. The creation of this vast database may help integrate the vascular aspects of glaucoma into the clinical practice of glaucoma. PMID- 26895611 TI - [Contribution of Anales de Pediatria to the international visibility of Spanish paediatric research in the Web of Science (2010-2014)]. AB - OBJECTIVE: To describe the role of Anales de Pediatria in highlighting Spanish paediatric research, and to identify the journals with which it competes internationally. MATERIAL AND METHOD: Spanish paediatric articles, including those from Anales de Pediatria were identified using the Paediatrics category of the Science Citation Index (2010-2014), and their volume and document type was analysed. For original articles and review articles, the year, the citation and journal of publication was studied. The journals were classified as general and specialised. The productivity of general journals was analysed according to their language, JCR quartile, and article access. RESULTS: A total of 2,701 Spanish paediatric papers were identified, accounting for 2.8% of the paediatrics world output. More than two-thirds (68%) of papers were articles that received an average number of 4.97 citations per article. The 965 papers published in Anales de Pediatria accounted for 38.7% of the Spanish paediatric output, and for 1% of the paediatric world publications. A mean of 1.03 citations per article were received for 439 (45.4%) articles and reviews. Of the 106 journals identified, 82 were classified as specialised (1,196 articles) and 24 as general (741 articles). Anales de Pediatria published 60% of the articles in general journals. The rest of articles (309) were published in general journals published in English (82.8%), with a best position in the JCR ranking (83.4%) and mainly by subscription (73.8%). CONCLUSIONS: Anales de Pediatria plays an important role in providing international visibility to a large volume of Spanish scientific production in paediatrics. The results presented are a still only a snapshot of this role that could be used in the near future for assessing its evolution and the changes that could be made in order to improve its quality, positioning and competitiveness. PMID- 26895612 TI - Macroscopic techniques for ophthalmic tumor specimens. AB - This article explores the range of tumor specimens that may be submitted to ophthalmic pathology. The handling of complex enucleation and exenteration is described along with smaller eyelid, conjunctival and corneal specimens. The importance of a good understanding of the unique anatomy of the ocular region and detailed clinical information is emphasized as this results in the taking of appropriate blocks for histology and consequently clinically helpful reports. Recommendations for handling specimens where further tissue is required for molecular studies is discussed. PMID- 26895613 TI - Fine and ultrafine particle exposures on 73 trips by car to 65 non-smoking restaurants in the San Francisco Bay Area. AB - A number of studies indicate cooking is a major source of exposure to particulate matter, but few studies have measured indoor air pollution in restaurants, where cooking predominates. We made 73 visits by car to 65 different non-smoking restaurants in 10 Northern California towns while carrying portable continuous monitors that unobtrusively measured ultrafine (down to 10 nm) and fine (PM2.5 ) particles to characterize indoor restaurant exposures, comparing them with exposures in the car. The mean ultrafine number concentrations in the restaurants on dinner visits averaging 1.4 h was 71 600 particles/cm3 , or 4.3 times the mean concentration on car trips, and 12.3 times the mean background concentration in the residence. Restaurants that cooked dinner in the same room as the patrons had higher ultrafine concentrations than restaurants with separate kitchens. Restaurant PM2.5 mass concentrations averaged 36.3 MUg/m3 , ranging from 1.5 to 454 MUg/m3 , but were relatively low on most visits: 43% of the indoor means were below 10 MUg/m3 and 66% were below 20 MUg/m3 , with 5.5% above 100 MUg/m3 . Exposure to fine and ultrafine particles when visiting a restaurant exceeded the exposure a person received while traveling by car to and from the restaurant. PMID- 26895614 TI - Obstructive sleep apnoea and the need for its introduction into dental curricula. AB - Obstructive sleep apnoea (OSA) is a major health problem which causes blood oxygen desaturation that may initiate a cascade of events via inflammatory cytokines and adrenocorticotrophic hormone that may have impact upon quality of life and lead to potential life-threatening events. Even though OSA affects an increasing number of individuals, the role of dental practitioners in recognition, screening and management has not developed accordingly. The goal of this article was to provide updated information to dental practitioners on pathophysiology, consequences and treatment options of OSA with a focused discussion on oral appliance (OA) therapy, as this topic is not routinely included in current dental curricula of many dental schools. Additionally, we present a template dental curriculum for predoctoral and/or postdoctoral students in education regarding sleep disordered breathing. PMID- 26895615 TI - Surgical Therapies and Tissue Engineering: At the Intersection Between Innovation and Regulation. PMID- 26895616 TI - Preventing ventriculostomy-related infections with antibiotic-impregnated drains in hospitals: a two-centre Dutch study. AB - This observational cohort study assessed the effect of the introduction of antibiotic-impregnated external ventricular drains (AI-EVDs), as opposed to plain silicone EVDs, on the occurrence of ventriculostomy-related infections (VRIs) in two Dutch hospitals, with no other changes to their clinical practice. VRI was defined using the criteria of the Centers for Disease Control and Prevention, and with a culture-based definition. A propensity-score-adjusted competing risks survival analysis showed that introduction of AI-EVDs did not significantly decrease the risk of VRIs in routine care, nor affect the bacterial aetiology, even after adjustment for confounding and competing events. PMID- 26895617 TI - Environmental decontamination following occupancy of a burns patient with multiple carbapenemase-producing organisms. AB - Over the last decade, carbapenemase-producing organisms (CPOs) have spread worldwide, becoming a major public health concern. This article reports the authors' experience in dealing with a burns patient infected with CPOs, and the decontamination methods employed to render a burns shock room safe for re-use. The shock room was cleaned after being vacated, but environmental sampling cultured multiple CPOs. A second decontamination was undertaken comprising a detergent, steam and hypochlorite clean followed by hydrogen peroxide misting, and no CPOs were cultured after subsequent environmental sampling. A burns patient harbouring CPOs contaminates the surroundings heavily, so standard cleaning is insufficient to reduce the environmental bioburden. PMID- 26895618 TI - Changes in intrafollicular concentrations of free IGF-1, activin A, inhibin A, VEGF, estradiol, and prolactin before ovulation in mares. AB - Changes in intrafollicular growth factors and hormones were evaluated in vivo in postdeviation and impending ovulation follicles. Mares (n = 30) were randomly assigned to five experimental groups based on target diameters of 25, 30, 35, 40 mm, and impending signs of ovulation. Furthermore, data belonging to two or more proximal diameter groups that were not different were combined and regrouped for each factor separately. Follicular fluid-free insulin-like growth factor 1 was highest (P < 0.003) in 35-mm follicles, followed by the 40-mm and impending ovulation follicle group, and the 25- to 30-mm follicle group. However, concentrations of insulin-like growth factor binding protein 2 in follicular fluid did not differ (P > 0.05) among groups. Additionally, follicular fluid activin A tended (P < 0.06) to be higher in impending ovulation follicles when compared with the 25- to 40-mm follicle group. Concentrations of intrafollicular estradiol were higher (P < 0.0001) in 40-mm and impending ovulation follicles than in the other follicle groups. Follicular fluid concentrations of inhibin A and vascular endothelial growth factor were lower (P < 0.05) in the 40-mm and the impending ovulation follicle group when compared with the 25- to 35-mm follicle group. Systemic and intrafollicular prolactin levels were lower (P < 0.05) in the impending ovulation group when compared with the 25- to 40-mm follicle group. Prolactin concentrations were higher (P < 0.05) in the follicular fluid than in the plasma. The novel findings of this study, a decrease in intrafollicular-free insulin-like growth factor 1, inhibin A, vascular endothelial growth factor, and prolactin during the final stages of follicular growth, document for the first time the occurrence of dynamic changes among intrafollicular factors and hormones during the stages of follicle dominance and as ovulation approaches. PMID- 26895619 TI - Kartogenin treatment prevented joint degeneration in a rodent model of osteoarthritis: A pilot study. AB - Osteoarthritis (OA) is a major degenerative joint disease characterized by progressive loss of articular cartilage, synovitis, subchondral bone changes, and osteophyte formation. Currently there is no treatment for OA except temporary pain relief and end-stage joint replacement surgery. We performed a pilot study to determine the effect of kartogenin (KGN, a small molecule) on both cartilage and subchondral bone in a rat model of OA using multimodal imaging techniques. OA was induced in rats (OA and KGN treatment group) by anterior cruciate ligament transection (ACLT) surgery in the right knee joint. Sham surgery was performed on the right knee joint of control group rats. KGN group rats received weekly intra articular injection of 125 MUM KGN 1 week after surgery until week 12. All rats underwent in vivo magnetic resonance imaging (MRI) at 3, 6, and 12 weeks after surgery. Quantitative MR relaxation measures (T1rho and T2 ) were determined to evaluate changes in articular cartilage. Cartilage and bone turnover markers (COMP and CTX-I) were determined at baseline, 3, 6, and 12 weeks. Animals were sacrificed at week 12 and the knee joints were removed for micro-computed tomography (micro-CT) and histology. KGN treatment significantly lowered the T1rho and T2 relaxation times indicating decreased cartilage degradation. KGN treatment significantly decreased COMP and CTX-I levels indicating decreased cartilage and bone turnover rate. KGN treatment also prevented subchondral bone changes in the ACLT rat model of OA. Thus, kartogenin is a potential drug to prevent joint deterioration in post-traumatic OA. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1780-1789, 2016. PMID- 26895620 TI - Current status of percutaneous right ventricular assist devices: First-in-man use of a novel dual lumen cannula. AB - Ventricular assist devices have become an accepted therapeutic solution for patients with severe left ventricular dysfunction when pharmacology fails to maintain sufficient cardiac output. Despite various technologies that have allowed left ventricular assist devices to become more reliable and versatile in the past decade, comparatively little attention has been applied to right heart assistance which is still in the early stage of its development. The extracorporeal devices developed thus far have been associated with mobility issues and complications common to ventricular assist devices in general, such as infection, bleeding, and thromboembolism. Designed to obviate the problems previously experienced by other right ventricle (RV)-focused devices, the Protek Duo (CardiacAssist, Pittsburgh, PA) is a novel, fully percutaneous, dual lumen cannula for RV support used in conjunction with the paracorporeal TandemHeart((r)) (CardiacAssist, Pittsburgh, PA) pump. We describe our initial experience with the Protek Duo cannula in two different clinical scenarios. In addition, we summarize the current percutaneous mechanical support technology for RV assistance and propose modification of current technology to facilitate its application. (c) 2016 Wiley Periodicals, Inc. PMID- 26895621 TI - Safety, Costs, and Efficacy of Rapid Drug Desensitizations to Chemotherapy and Monoclonal Antibodies. AB - BACKGROUND: Rapid drug desensitization (RDD) is used to address hypersensitivity reactions to chemotherapeutics and monoclonal antibodies, allowing patients to be treated with optimal pharmacological agents. RDD protocols are tailored to each individual patient's reaction and needs, and protect against anaphylaxis, but overall risks, costs, and benefits have not been determined. OBJECTIVE: We investigated the safety, efficacy, costs, and life expectancy of patients in a large population undergoing RDD. METHODS: We analyzed 2177 RDD procedures performed in 370 patients with cancer, vasculitis, and hematological and connective tissue diseases who presented 402 reactions. A subgroup of carboplatin allergic patients with ovarian cancer treated with RDD was analyzed for costs and life expectancy and compared with a nonallergic control group. RESULTS: RDD allowed all patients to receive safely the full dose of the medication to which they were reactive. A gradual increase in the fraction of outpatient desensitizations from 81% to 98% was achieved through risk stratification. Of the 2177 desensitizations, 93% had no or mild reactions whereas 7% had moderate to severe reactions, which did not preclude the completion of the treatment, and there were no deaths. Overall health costs in the carboplatin allergic group were not higher than those in the nonallergic group treated with standard of care. Administration of carboplatin through RDD was as effective as standard administration with a nonsignificant increase in life expectancy in desensitized patients as compared with nonallergic, nondesensitized controls. CONCLUSIONS: RDD is cost effective and safe for allergic patients with cancer and chronic disease to remain on first line therapy. PMID- 26895622 TI - Bioaugmentation Mitigates the Impact of Estrogen on Coliform-Grazing Protozoa in Slow Sand Filters. AB - Exposure to endocrine-disrupting chemicals (EDCs), such as estrogens, is a growing issue for human and animal health as they have been shown to cause reproductive and developmental abnormalities in wildlife and plants and have been linked to male infertility disorders in humans. Intensive farming and weather events, such as storms, flash flooding, and landslides, contribute estrogen to waterways used to supply drinking water. This paper explores the impact of estrogen exposure on the performance of slow sand filters (SSFs) used for water treatment. The feasibility and efficacy of SSF bioaugmentation with estrogen degrading bacteria was also investigated, to determine whether removal of natural estrogens (estrone, estradiol, and estriol) and overall SSF performance for drinking water treatment could be improved. Strains for SSF augmentation were isolated from full-scale, municipal SSFs so as to optimize survival in the laboratory-scale SSFs used. Concentrations of the natural estrogens, determined by gas chromatography coupled with mass spectrometry (GC-MS), revealed augmented SSFs reduced the overall estrogenic potency of the supplied water by 25% on average and removed significantly more estrone and estradiol than nonaugmented filters. A negative correlation was found between coliform removal and estrogen concentration in nonaugmented filters. This was due to the toxic inhibition of protozoa, indicating that high estrogen concentrations can have functional implications for SSFs (such as impairing coliform removal). Consequently, we suggest that high estrogen concentrations could impact significantly on water quality production and, in particular, on pathogen removal in biological water filters. PMID- 26895624 TI - Restless legs syndrome in Belgian repeat blood donors, no correlation with ferritin level. PMID- 26895623 TI - Surveillance of effects of HPV vaccination in Belgium. AB - BACKGROUND: Early effects of HPV (human papillomavirus) vaccination are reflected by changes observable in young women attending cervical cancer screening. SUBJECT AND METHODS: The SEHIB study included HPV geno-typing of ~6000 continuous and 650 pathological cervical cell specimen as well as biopsies, collected from women in Belgium in 2010-2014. Data were linked to vaccination status. RESULTS: HPV vaccination offered protection among women aged <30years against infection with HPV16 (vaccine effectiveness [VE]=67%, 95% CI: 48-79%), HPV18 (VE=93%, 95% CI: 52 99%), and high-risk HPV (VE=16%, 95% CI: 2-29%). Vaccination protected also against cytological lesions. Vaccination protected against histologically confirmed lesions: significantly lower absolute risks of CIN1+ (risk difference [RD]=-1.6%, 95% CI: -2.6% to -0.7%) and CIN3+ associated with HPV16/18 (RD=-0.3%, 95% CI -0.6% to -0.1%). Vaccine effectiveness decreased with age. Protection against HPV16 and 18 infection was significant in all age groups, however no protection was observed against cytological lesions associated with these types in age-group 25-29. CONCLUSION: The SEHIB study demonstrates the effectiveness of HPV vaccination in Belgian young women in particular in age group 18-19. Declining effectiveness with increasing age may be explained by higher tendency of women already exposed to infection to get the vaccine. PMID- 26895625 TI - Screening and characterization of amylase and cellulase activities in psychrotolerant yeasts. AB - BACKGROUND: Amylases and cellulases have great potential for application in industries such as food, detergent, laundry, textile, baking and biofuels. A common requirement in these fields is to reduce the temperatures of the processes, leading to a continuous search for microorganisms that secrete cold active amylases and cellulases. Psychrotolerant yeasts are good candidates because they inhabit cold-environments. In this work, we analyzed the ability of yeasts isolated from the Antarctic region to grow on starch or carboxymethylcellulose, and their potential extracellular amylases and cellulases. RESULT: All tested yeasts were able to grow with soluble starch or carboxymethylcellulose as the sole carbon source; however, not all of them produced ethanol by fermentation of these carbon sources. For the majority of the yeast species, the extracellular amylase or cellulase activity was higher when cultured in medium supplemented with glucose rather than with soluble starch or carboxymethylcellulose. Additionally, higher amylase activities were observed when tested at pH 5.4 and 6.2, and at 30-37 degrees C, except for Rhodotorula glacialis that showed elevated activity at 10-22 degrees C. In general, cellulase activity was high until pH 6.2 and between 22-37 degrees C, while the sample from Mrakia blollopis showed high activity at 4-22 degrees C. Peptide mass fingerprinting analysis of a potential amylase from Tetracladium sp. of about 70 kDa, showed several peptides with positive matches with glucoamylases from other fungi. CONCLUSIONS: Almost all yeast species showed extracellular amylase or cellulase activity, and an inducing effect by the respective substrate was observed in a minor number of yeasts. These enzymatic activities were higher at 30 degrees C in most yeast, with highest amylase and cellulase activity in Tetracladium sp. and M. gelida, respectively. However, Rh. glacialis and M. blollopis displayed high amylase or cellulase activity, respectively, under 22 degrees C. In this sense, these yeasts are interesting candidates for industrial processes that require lower temperatures. PMID- 26895628 TI - Ghost busting--taking the sheet off the ghost. PMID- 26895627 TI - Feline panleukopenia virus in cerebral neurons of young and adult cats. AB - BACKGROUND: Perinatal infections with feline panleukopenia virus (FPV) have long been known to be associated with cerebellar hypoplasia in kittens due to productive infection of dividing neuroblasts. FPV, like other parvoviruses, requires dividing cells to replicate which explains the usual tropism of the virus for the digestive tract, lymphoid tissues and bone marrow in older animals. RESULTS: In this study, the necropsy and histopathological analyses of a series of 28 cats which died from parvovirus infection in 2013 were performed. Infections were confirmed by real time PCR and immunohistochemistry in several organs. Strikingly, while none of these cats showed cerebellar atrophy or cerebellar positive immunostaining, some of them, including one adult, showed a bright positive immunostaining for viral antigens in cerebral neurons (diencephalon). Furthermore, infected neurons were negative by immunostaining for p27(Kip1), a cell cycle regulatory protein, while neighboring, uninfected, neurons were positive, suggesting a possible re-entry of infected neurons into the mitotic cycle. Next-Generation Sequencing and PCR analyses showed that the virus infecting cat brains was FPV and presented a unique substitution in NS1 protein sequence. Given the role played by this protein in the control of cell cycle and apoptosis in other parvoviral species, it is tempting to hypothesize that a cause-to-effect between this NS1 mutation and the capacity of this FPV strain to infect neurons in adult cats might exist. CONCLUSIONS: This study provides the first evidence of infection of cerebral neurons by feline panleukopenia virus in cats, including an adult. A possible re-entry into the cell cycle by infected neurons has been observed. A mutation in the NS1 protein sequence of the FPV strain involved could be related to its unusual cellular tropism. Further research is needed to clarify this point. PMID- 26895626 TI - Generation of aggregation prone N-terminally truncated amyloid beta peptides by meprin beta depends on the sequence specificity at the cleavage site. AB - BACKGROUND: The metalloprotease meprin beta cleaves the Alzheimer's Disease (AD) relevant amyloid precursor protein (APP) as a beta-secretase reminiscent of BACE 1, however, predominantly generating N-terminally truncated Abeta2-x variants. RESULTS: Herein, we observed increased endogenous sAPPalpha levels in the brains of meprin beta knock-out (ko) mice compared to wild-type controls. We further analyzed the cellular interaction of APP and meprin beta and found that cleavage of APP by meprin beta occurs prior to endocytosis. The N-terminally truncated Abeta2-40 variant shows increased aggregation propensity compared to Abeta1-40 and acts even as a seed for Abeta1-40 aggregation. Additionally, we observed that different APP mutants affect the catalytic properties of meprin beta and that, interestingly, meprin beta is unable to generate N-terminally truncated Abeta peptides from Swedish mutant APP (APPswe). CONCLUSION: Concluding, we propose that meprin beta may be involved in the generation of N-terminally truncated Abeta2-x peptides of APP, but acts independently from BACE-1. PMID- 26895629 TI - Prevalence of musculoskeletal disorders and rheumatic disease in the Warao, Kari'na, and Chaima indigenous populations of Monagas State, Venezuela. AB - This study aimed to estimate the prevalence of musculoskeletal disorders and rheumatic diseases in the Warao, Kari'na, and Chaima indigenous populations of Monagas State, Venezuela. A cross-sectional, analytical, community-based study was conducted in 1537 indigenous subjects >=18 years old (38.6 % male, mean age 41.4 +/- 17.5 years). The cross-culturally validated Community Oriented Program for the Control of Rheumatic Diseases (COPCORD) diagnostic questionnaire was applied. Subjects with a positive COPCORD diagnosis (either historic or current pain) were evaluated by primary care physicians and rheumatologists. A descriptive analysis was performed and comparisons made using analysis of variance and the chi-square test. Pain in the last 7 days was reported by 32.9 %, with pain intensity, according to a Likert-type scale [no pain, 195 (38.5 %); minimal pain, 231 (45.6 %); strong pain, 68 (13.4 %); intense pain, 5 (0.9 %)], 38.0 % reported historical pain, and 641 (41.7 %) had either historic or current pain. Of the COPCORD-positive subjects, pain most frequently occurred in the knee, back, and hands. Musculoskeletal and rheumatic diseases included osteoarthritis (14.1 %), back pain (12.4 %), rheumatic regional pain syndromes (RRPS) (9.7 %), undifferentiated arthritis (1.5 %), rheumatoid arthritis (1.1 %), and fibromyalgia (0.5 %). Chaima (18.3 %) and Kari'na (15.6 %) subjects had a high prevalence of osteoarthritis, and Warao subjects had a high prevalence of low back pain (13.8 %). The prevalence of RRPS was high in all three ethnic groups. The Chaima group had the highest prevalence of rheumatic diseases, with 2.0 % having rheumatoid arthritis. This study provides useful information for health care policy-making in indigenous communities. PMID- 26895630 TI - PME58 plays a role in pectin distribution during seed coat mucilage extrusion through homogalacturonan modification. AB - Pectins are major components of plant primary cell walls. They include homogalacturonans (HGs), which are the most abundant pectin and can be the target of apoplastic enzymes like pectin methylesterases (PMEs) that control their methylesterification level. Several PMEs are expressed in the seed coat of Arabidopsis thaliana, particularly in mucilage secretory cells (MSCs). On the basis of public transcriptomic data, seven PME genes were selected and checked for their seed-specific expression by quantitative reverse transcription PCR. Of these, PME58 presented the highest level of expression and was specifically expressed in MSCs at the early stages of seed development. pme58 mutants presented two discrete phenotypes: (i) their adherent mucilage was less stained by ruthenium red when compared to wild-type seeds, but only in the presence of EDTA, a Ca(2+)chelator; and (ii) the MSC surface area was decreased. These phenotypes are the consequence of an increase in the degree of HG methylesterification connected to a decrease in PME activity. Analysis of the sugar composition of soluble and adherent mucilage showed that, in the presence of EDTA, sugars of adherent mucilage were more readily extracted in pme58 mutants. Immunolabelling with LM19, an antibody that preferentially recognizes unesterified HGs, also showed that molecular interactions with HGs were modified in the adherent mucilage of pme58 mutants, suggesting a role of PME58 in mucilage structure and organization. In conclusion, PME58 is the first PME identified to play a direct role in seed mucilage structure. PMID- 26895631 TI - Rat-atouille: A Mixed Method Study to Characterize Rodent Hunting and Consumption in the Context of Lassa Fever. AB - Lassa fever is a zoonotic hemorrhagic illness predominant in areas across Nigeria, Sierra Leone, Guinea, Liberia, and southern Mali. The reservoir of Lassa virus is the multimammate mouse (Mastomys natalensis), a highly commensal species in West Africa. Primary transmission to humans occurs through direct or indirect contact with rodent body fluids such as urine, feces, saliva, or blood. Our research draws together qualitative and quantitative methods to provide a fuller and more nuanced perspective on these varied points of human-animal contact. In this article, we focus on the hunting, preparation, and consumption of rodents as possible routes of exposure in Bo, Sierra Leone. We found that the consumption of rodents, including the reservoir species, is widespread and does not neatly tally against generational or gender lines. Further, we found that the reasons for rodent consumption are multifactorial, including taste preferences, food security, and opportunistic behavior. We argue that on certain topics, such as rodent consumption, establishing trust with communities, and using qualitative research methods, is key to investigate sensitive issues and situate them in their wider context. To conclude, we recommend ways to refine sensitization campaigns to account for these socio-cultural contexts. PMID- 26895634 TI - Fifty years of longitudinal continuity in general practice: a retrospective observational study. AB - BACKGROUND: Continuity of care has been defined as relational continuity between patient and doctor and longitudinal continuity describing the duration of the relationship. Measurement of longitudinal continuity alone is associated with outcomes including patient satisfaction, medical costs, hospital admissions and mortality. METHODS: In one UK general practice, records were searched for patients with continuous registration for 50 or more years. Characteristics of these patients were analysed for age, gender, social deprivation, partner registration and length of registration. Trends in numbers and proportions of this group over the previous 14 years were determined. A comparison group of patients, aged 50 or more, and registered in the same practice within the last 2 4 years, was identified. RESULTS: Patients registered for 50 years or more with a median registration of 56.2 years numbered 190 out of a population of 8420 (2.3%). These patients increased in number by 35.3% (1.7-2.3%) over 14 consecutive years. There were no differences between groups for GP consultation rate, number of repeat medications and hospital use, despite the significantly higher prevalence of multi-morbidity, depression and diabetes in patients with high continuity. CONCLUSIONS: This is the first report of 50-year continuity in general practice. Numbers of such patients and proportions are increasing. Longitudinal continuity is easily measured in general practice and associated with important clinical outcomes. PMID- 26895632 TI - Pancreatic panniculitis in a patient with pancreatic-type acinar cell carcinoma of the liver--case report and review of literature. AB - BACKGROUND: Pancreatic panniculitis is a rare condition, which has only been described in relation with pancreatic diseases up to now. It is characterized by necrotizing subcutaneous inflammation and is thought to be triggered by adipocyte necrosis due to systemic release of pancreatic enzymes with consecutive infiltration of neutrophils. We present the first case of a patient with pancreatic panniculitis caused by pancreatic-type primary acinar cell carcinoma (ACC) of the liver and without underlying pancreatic disease. CASE PRESENTATION: A 73-year old Caucasian female patient was referred to our department with painful cutaneous nodules persisting for eight weeks and with marked lipasemia (~15000 U/l; normal range <60 U/l). Four weeks prior, several liver lesions had been detected. Empiric treatment with steroids did not show any effect. A biopsy of the skin nodules revealed "pancreatic" panniculitis, while abdominal imaging with ultrasound, computed tomography and magnetic resonance imaging detected no abnormal pancreatic findings. Ultrasound-guided biopsy of the liver lesions showed infiltrates of an ACC. The patient died soon thereafter. Autopsy failed to reveal any other primary for the ACC, so that a pancreatic-type ACC of the liver was diagnosed by exclusion. One hundred thirty cases of pancreatic panniculitis published within the last 20 years are reviewed. ACC of the pancreas is the most common underlying neoplastic condition. Patients with associated neoplasm are significantly older, take longer to be diagnosed and have higher lipase levels than patients with underlying pancreatitis. Extrapancreatic pancreatic-type ACC is very rare, but shows the same biological features as ACC of the pancreas. It is believed to develop from metaplastic or ectopic pancreatic tissue. Up to now, no pancreatic panniculitis in extrapancreatic ACC has been described. CONCLUSION: Pancreatic panniculitis should always be included in the differential diagnosis of lipolytic panniculitic lesions. It can be regarded as a facultative paraneoplastic phenomenon. When suspected, a thorough work-up for identification of the underlying disease is mandatory and extrapancreatic lesions (e.g. liver) should also be considered. While administration of octreotide or steroids can sometimes alleviate symptoms, immediate treatment of the associated condition is the only effective management option. PMID- 26895635 TI - The cytokine profile of human NKT cells and PBMCs is dependent on donor sex and stimulus. AB - Sex-related variations in natural killer T (NKT) cells may influence immunoregulation and outcome of infectious and autoimmune diseases. We analyzed sex-specific differences in peripheral blood NKTs and peripheral blood mononuclear cells (PBMCs) from men and women and determined the frequencies of NKT cells and their subpopulations [CD4(+); CD8(+); double negative (DN)] and the levels of cytokine production following stimulation with the NKT cell ligands alpha-Galactosylceramide (alphaGalCer) and Entamoeba histolytica lipopeptidephosphoglycan (Lotter et al. in PLoS Pathog 5(5):e1000434, 2009). Total and DN NKT cells were more abundant in women than in men. In women, alphaGalCer induced higher production of intracellular IFNgamma, IL-4, IL-17 and TNF by CD4(+) and DN(+)NKT cells. Both ligands induced expression of multiple cytokines in PBMCs and influenced the ratio of NKT cell subpopulations during long-term culture. Although the sex-specific differences in frequencies of NKT cells and their subpopulations were marginal, the significant sex-specific differences in cytokine production might influence disease outcomes. PMID- 26895636 TI - Could body mass index be an indicator for endometrial biopsy in premenopausal women with heavy menstrual bleeding? AB - PURPOSE: To evaluate the role of body mass index (BMI) in women with premenopausal heavy menstrual bleeding (HMB) to identify patients who should undergo endometrial biopsy. METHODS: This prospective cohort study included 1120 premenopausal women who presented to the Gynecology Clinic, Bakirkoy Dr. Sadi Konuk Training and Research Hospital in Istanbul, Turkey, due to HMB and who underwent endometrial sampling. The abnormal endometrial histopathological results were analyzed by separating patients into groups of all abnormal findings (hyperplasia without atypia + hyperplasia with atypia + carcinoma) and hyperplasia with atypia + carcinoma. Sensitivity and specificity of the abnormal histopathological results were calculated in both groups using BMI cut-off values as 25, 30 and 35 and age cut-offs as 40 and 45 years. RESULTS: The rate of hyperplasia with atypia and carcinoma was sevenfold higher in women with a BMI >=30 compared to those with a BMI <=30 (95 % CI 2.4-17.9). In the analyses, BMI was a stronger risk factor in women younger than 45 years of age. The risk of endometrial carcinoma and atypical hyperplasia was twofold higher in patients older than 45 years when compared with patients younger than 45 years (95 % CI 1.1-5.1). CONCLUSIONS: All women with a BMI >=30 and presenting premenopausal HMB should undergo endometrial biopsy regardless of age. PMID- 26895633 TI - Treatment of periodontal intrabony defects using autologous periodontal ligament stem cells: a randomized clinical trial. AB - BACKGROUND: Periodontitis, which progressively destroys tooth-supporting structures, is one of the most widespread infectious diseases and the leading cause of tooth loss in adults. Evidence from preclinical trials and small-scale pilot clinical studies indicates that stem cells derived from periodontal ligament tissues are a promising therapy for the regeneration of lost/damaged periodontal tissue. This study assessed the safety and feasibility of using autologous periodontal ligament stem cells (PDLSCs) as an adjuvant to grafting materials in guided tissue regeneration (GTR) to treat periodontal intrabony defects. Our data provide primary clinical evidence for the efficacy of cell transplantation in regenerative dentistry. METHODS: We conducted a single-center, randomized trial that used autologous PDLSCs in combination with bovine-derived bone mineral materials to treat periodontal intrabony defects. Enrolled patients were randomly assigned to either the Cell group (treatment with GTR and PDLSC sheets in combination with Bio-oss((r))) or the Control group (treatment with GTR and Bio-oss((r)) without stem cells). During a 12-month follow-up study, we evaluated the frequency and extent of adverse events. For the assessment of treatment efficacy, the primary outcome was based on the magnitude of alveolar bone regeneration following the surgical procedure. RESULTS: A total of 30 periodontitis patients aged 18 to 65 years (48 testing teeth with periodontal intrabony defects) who satisfied our inclusion and exclusion criteria were enrolled in the study and randomly assigned to the Cell group or the Control group. A total of 21 teeth were treated in the Control group and 20 teeth were treated in the Cell group. All patients received surgery and a clinical evaluation. No clinical safety problems that could be attributed to the investigational PDLSCs were identified. Each group showed a significant increase in the alveolar bone height (decrease in the bone-defect depth) over time (p < 0.001). However, no statistically significant differences were detected between the Cell group and the Control group (p > 0.05). CONCLUSIONS: This study demonstrates that using autologous PDLSCs to treat periodontal intrabony defects is safe and does not produce significant adverse effects. The efficacy of cell based periodontal therapy requires further validation by multicenter, randomized controlled studies with an increased sample size. TRIAL REGISTRATION: NCT01357785 Date registered: 18 May 2011. PMID- 26895638 TI - Developing Sound Skills for Reading: Teaching Phonological Awareness to Preschoolers With Hearing Loss. AB - This study evaluated the effectiveness of intervention for developing deaf and hard-of-hearing (DHH) preschoolers' phonological awareness (PA) skills. Thirty children (mean age 57 months) with aided, bilateral hearing loss (and who primarily communicated using spoken English) were recruited in the year prior to commencing formal schooling. The study used an experimental design with participants assigned to one of two intervention conditions-vocabulary instruction, or explicit PA instruction. Both intervention programs were based around items drawn from a common word set and presented over six short weekly sessions by a researcher using a computer tablet. Overall, participants showed greater knowledge of word items used in interventions and improved performance on rhyme-based PA skills following intervention. However, the PA group showed significantly greater improvement than the vocabulary group for both overall PA performance and for consonant-vowel-consonant blending. DHH children's order of PA skill development was also examined, with comparison to that shown for children without hearing loss. The results provide early encouraging evidence about the potential benefit of explicit PA instruction for this population. PMID- 26895639 TI - Major changes proposed for NHS in Scotland. PMID- 26895637 TI - Mammary-tumor-educated B cells acquire LAP/TGF-beta and PD-L1 expression and suppress anti-tumor immune responses. AB - B lymphocytes play a role in inhibiting the immune response against certain tumors, but the underlying mechanisms are poorly understood. EMT-6 mammary tumors grow well in wild-type (WT) mice but show reduced growth in B-cell-deficient MU( /-) BALB/c mice (BCDM). WT mice demonstrate extensive B-cell infiltration into the tumor bed, reduced CD8(+) T cell and CD49(+) NK cell infiltration, and markedly reduced cytolytic T-cell response relative to BCDM. Expression of LAP/TGF-beta1, CD80, CD86 and PD-L1 is significantly increased in tumor infiltrating B cells (TIL-B) relative to splenic B cells. LAP/TGF-beta1 expression on TIL-B progressively increased from 5.4+/-1.7% on day 8 to 43.1+/ 6.1% by day 21 post tumor implantation. Co-culture of EMT-6 tumor cells with Naive-B cells ex vivo generated B cells (EMT6-B) with a similar immunophenotype to TIL-B. Purified TIL-B, or in-vitro-generated EMT6-B suppressed CD4(+), CD8(+) and CD4(+)CD25(-) T-cell proliferation, and Th1 cytokine secretion, and also suppressed purified NK-cell proliferation in response to IL-15, compared to naive splenic B cells. Acquired B regulatory function required direct tumor cell: B cell contact, and was partially reversed by antibody to TGF-beta or PD-L1, leading to tumor rejection in vivo B-cell acquisition of a suppressive phenotype following tumor infiltration may result in profound inhibition of T-cell anti tumor responses. PMID- 26895642 TI - Revisiting the panculture. PMID- 26895641 TI - Integrating Publicly Available Data to Generate Computationally Predicted Adverse Outcome Pathways for Fatty Liver. AB - Newin vitrotesting strategies make it possible to design testing batteries for large numbers of environmental chemicals. Full utilization of the results requires knowledge of the underlying biological networks and the adverse outcome pathways (AOPs) that describe the route from early molecular perturbations to an adverse outcome. Curation of a formal AOP is a time-intensive process and a rate limiting step to designing these test batteries. Here, we describe a method for integrating publicly available data in order to generate computationally predicted AOP (cpAOP) scaffolds, which can be leveraged by domain experts to shorten the time for formal AOP development. A network-based workflow was used to facilitate the integration of multiple data types to generate cpAOPs. Edges between graph entities were identified through direct experimental or literature information, or computationally inferred using frequent itemset mining. Data from the TG-GATEs and ToxCast programs were used to channel large-scale toxicogenomics information into a cpAOP network (cpAOPnet) of over 20 000 relationships describing connections between chemical treatments, phenotypes, and perturbed pathways as measured by differential gene expression and high-throughput screening targets. The resulting fatty liver cpAOPnet is available as a resource to the community. Subnetworks of cpAOPs for a reference chemical (carbon tetrachloride, CCl4) and outcome (fatty liver) were compared with published mechanistic descriptions. In both cases, the computational approaches approximated the manually curated AOPs. The cpAOPnet can be used for accelerating expert-curated AOP development and to identify pathway targets that lack genomic markers or high-throughput screening tests. It can also facilitate identification of key events for designing test batteries and for classification and grouping of chemicals for follow up testing. PMID- 26895640 TI - Behaviours and attitudes influencing treatment decisions for menopausal symptoms in five European countries. AB - OBJECTIVE: To assess women's behaviours and attitudes regarding the treatment of menopausal symptoms in five European countries. STUDY DESIGN: Women aged >=45 years in France, Germany, Italy, Spain, and the United Kingdom participated in an internet survey. Completers were those who reported menopausal symptoms and had treated their symptoms. Women were equally stratified by age (45-54 years, 55-64 years, >=65 years). MAIN OUTCOME MEASURES: Behaviours, attitudes, and experiences regarding treatment of menopausal symptoms. RESULTS: Of 3890 peri- to postmenopausal women screened, 67% experienced symptoms and 54% sought either medical input or some treatment concerning their symptoms. Hot flushes, the most common symptom, decreased with age but remained prevalent after age 64. Roughly 75% of women who sought relief consulted a physician, mostly a gynaecologist or a general practitioner (GP) as in the United Kingdom. The decision to seek treatment was influenced by age, number, and severity of symptoms. Approximately 79% visiting a physician received prescription therapy. Of the women who received non-hormone therapy (HT) treatment instead of HT: patients refused HT (20-44%), physicians did not discuss HT (32-46%), or advised against HT (24-43%). Women in the United Kingdom were most familiar with and favorable to HT. Interest in a new HT (34-50%) was higher than use (19-28%). CONCLUSIONS: Menopausal symptoms are common, persistent, and bothersome, but many fail to seek treatment. Sources and types of treatment vary among age groups and countries. Education regarding women's attitudes toward treatment should be provided to those physicians who treat menopausal symptoms in each country. PMID- 26895643 TI - Involvement of gap junctions between smooth muscle cells in sustained hypoxic pulmonary vasoconstriction development: a potential role for 15-HETE and 20-HETE. AB - In response to hypoxia, the pulmonary artery normally constricts to maintain optimal ventilation-perfusion matching in the lung, but chronic hypoxia leads to the development of pulmonary hypertension. The mechanisms of sustained hypoxic pulmonary vasoconstriction (HPV) remain unclear. The aim of this study was to determine the role of gap junctions (GJs) between smooth muscle cells (SMCs) in the sustained HPV development and involvement of arachidonic acid (AA) metabolites in GJ-mediated signaling. Vascular tone was measured in bovine intrapulmonary arteries (BIPAs) using isometric force measurement technique. Expression of contractile proteins was determined by Western blot. AA metabolites in the bath fluid were analyzed by mass spectrometry. Prolonged hypoxia elicited endothelium-independent sustained HPV in BIPAs. Inhibition of GJs by 18beta glycyrrhetinic acid (18beta-GA) and heptanol, nonspecific blockers, and Gap-27, a specific blocker, decreased HPV in deendothelized BIPAs. The sustained HPV was not dependent on Ca(2+) entry but decreased by removal of Ca(2+) and by Rho kinase inhibition with Y-27632. Furthermore, inhibition of GJs decreased smooth muscle myosin heavy chain (SM-MHC) expression and myosin light chain phosphorylation in BIPAs. Interestingly, inhibition of 15- and 20 hydroxyeicosatetraenoic acid (HETE) synthesis decreased HPV in deendothelized BIPAs. 15-HETE- and 20-HETE-stimulated constriction of BIPAs was inhibited by 18beta-GA and Gap-27. Application of 15-HETE and 20-HETE to BIPAs increased SM MHC expression, which was also suppressed by 18beta-GA and by inhibitors of lipoxygenase and cytochrome P450 monooxygenases. More interestingly, 15,20 dihydroxyeicosatetraenoic acid and 20-OH-prostaglandin E2, novel derivatives of 20-HETE, were detected in tissue bath fluid and synthesis of these derivatives was almost completely abolished by 18beta-GA. Taken together, our novel findings show that GJs between SMCs are involved in the sustained HPV in BIPAs, and 15 HETE and 20-HETE, through GJs, appear to mediate SM-MHC expression and contribute to the sustained HPV development. PMID- 26895645 TI - [Spanish consensus statement for diagnosis and treatment of paroxysmal nocturnal haemoglobinuria]. AB - Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired clonal disorder of the haematopoietic progenitor cells due to a somatic mutation in theX-linked phosphatidylinositol glycan class A gene. The disease is characterized by intravascular haemolytic anaemia, propensity to thromboembolic events and bone marrow failure. Other direct complications of haemolysis include dysphagia, erectile dysfunction, abdominal pain, asthenia and chronic renal failure (65% of patients). The disease appears more often in the third decade of life and there is no sex or age preference. Detection of markers associated with glucosyl phosphatidyl inositol deficit by flow cytometry is currently used in the diagnosis of PNH. For years, transfusions have been the mainstay of therapy for PNH. A breakthrough in treatment has been the approval of the humanized monoclonal antibody eculizumab, which works by blocking the C5 complement protein, preventing its activation and therefore haemolysis. Several studies have confirmed that treatment with eculizumab avoids or decreases the need for transfusions, decreases the probability of thrombosis, improves the associated symptomatology and the quality of life in patients with PNH, showing an increase in survival. Because of rapid advances in the knowledge of the disease and its treatment, it may become necessary to adapt and standardize clinical guidelines for the management of patients with PNH. PMID- 26895644 TI - Enhanced resolution of experimental ARDS through IL-4-mediated lung macrophage reprogramming. AB - Despite intense investigation, acute respiratory distress syndrome (ARDS) remains an enormous clinical problem for which no specific therapies currently exist. In this study, we used intratracheal lipopolysaccharide or Pseudomonas bacteria administration to model experimental acute lung injury (ALI) and to further understand mediators of the resolution phase of ARDS. Recent work demonstrates macrophages transition from a predominant proinflammatory M1 phenotype during acute inflammation to an anti-inflammatory M2 phenotype with ALI resolution. We tested the hypothesis that IL-4, a potent inducer of M2-specific protein expression, would accelerate ALI resolution and lung repair through reprogramming of endogenous inflammatory macrophages. In fact, IL-4 treatment was found to offer dramatic benefits following delayed administration to mice subjected to experimental ALI, including increased survival, accelerated resolution of lung injury, and improved lung function. Expression of the M2 proteins Arg1, FIZZ1, and Ym1 was increased in lung tissues following IL-4 treatment, and among macrophages, FIZZ1 was most prominently upregulated in the interstitial subpopulation. A similar trend was observed for the expression of macrophage mannose receptor (MMR) and Dectin-1 on the surface of alveolar macrophages following IL-4 administration. Macrophage depletion or STAT6 deficiency abrogated the therapeutic effect of IL-4. Collectively, these data demonstrate that IL-4 mediated therapeutic macrophage reprogramming can accelerate resolution and lung repair despite delayed use following experimental ALI. IL-4 or other therapies that target late-phase, proresolution pathways may hold promise for the treatment of human ARDS. PMID- 26895647 TI - Risk factors for cattle presenting with a confirmed bTB lesion at slaughter, from herds with no evidence of within-herd transmission. AB - There has been a national bovine tuberculosis (bTB) eradication programme (BTBEP) in Ireland for many years. All cattle herds are tested at least annually using the Single Intradermal Comparative Tuberculin Test (SICTT). Further, abattoir surveillance is conducted on all animals at the time of slaughter. In the Irish BTBEP, a substantial number of confirmed bTB lesions are detected in non-reactor animals, to SICTT, from Officially Tuberculosis Free (OTF) herds at slaughter. In this study we investigate risk factors for non-reactor animals from OTF herds presenting with a confirmed bTB lesion at slaughter, but with no evidence of within-herd transmission. A case-control study was conducted, with animal as the unit of interest. The case animals were all SICTT non-reactor animals slaughtered in 2012, with a confirmed bTB lesion identified during routine abattoir surveillance and with no evidence of within-herd transmission. Control animals were selected from all SICTT non-reactor animals slaughtered in 2012 from OTF herds where no bTB lesion was found. Four controls matched by age (+/-1 year) and location (county) were randomly selected for each case. A conditional logistic regression model was developed for univariable and multivariable analysis. The final multivariable model included: number of movements, herd type, herd-size, inconclusive reactor status at any previous test, abattoir and time spent in a herd restricted for bTB. The odds of being a case increased with the number of times an animal had moved herds. Animals from suckler herds were significantly more likely to be a case compared to those from beef herds. The odds of being a case decreased with herd-size and increased as the time spent in a restricted herd increased. There were three key conclusions from this study. Firstly, the main risk factors for animals presenting with a confirmed bTB lesion at slaughter were: previous bTB exposure history, previous inconclusive reactor result at the SICTT, the number of herd movements and herd type/size. Secondly, there was very limited evidence that these animals could have been detected any earlier. Finally, there is a need to reconsider the importance of abattoir surveillance during the latter stages of an eradication campaign. As herd prevalence declines, an increasing proportion of herd restrictions will be triggered by a single bTB lesioned animal, with no evidence of within-herd transmission. PMID- 26895646 TI - Hospital-acquired functional decline in older patients cared for in acute medical wards and predictors: Findings from a multicentre longitudinal study. AB - Describing the trajectories of hospital-associated functional decline in older patients admitted to acute medical units and identifying predictors at the individual, nursing, and hospital levels, were the aims of the study. A longitudinal survey among 12 acute medical units in which 1464 patients were consecutively enrolled and evaluated using the Barthel Index (BI), was performed. Functional decline was defined as a decrease in the BI of at least 5 points from admission to discharge. In all, 17.1% participants (n = 251) demonstrated functional decline. In accordance with multiple logistic regression analysis, 28.8% (R(2)) of the variance in the functional decline was explained by: confusion/disorientation (RR = 4.684; 95% CI = 3.144-6.978), admission from nursing homes (RR = 2.464; 95% CI = 1.642-3.697), daily care expressed in minutes offered by nursing aides (RR = 1.535; 95% CI = 1.275-1.849), higher workforce skill-mix (RR = 2.221; 95% CI = 1.763-2.797), bladder catheter insertion (RR = 1.599; 95% CI = 1.128-2.268), and higher BI score at admission (RR = 1.019; 95% CI = 1.014-1.024). Increasing the amount of care delivered by competent nurses having a bachelors degree-providing and supervising direct-care activities, may reduce the occurrence of functional decline in older patients admitted to medical units. PMID- 26895648 TI - Combined effect of individual and neighborhood socioeconomic status on mortality in patients with newly diagnosed dyslipidemia: A nationwide Korean cohort study from 2002 to 2013. AB - BACKGROUND AND AIM: The study aims to determine whether dyslipidemia patients living in less affluent neighborhood are at a higher risk of mortality compared to those living in more affluent neighborhoods. METHODS AND RESULTS: A population based cohort study was conducted using a stratified representative sampling from the National Health Insurance claim data from 2002 to 2013. The target subjects comprise patients newly diagnosed with dyslipidemia receiving medication. We performed a survival analysis using the Cox proportional hazard model. Of 11,946 patients with dyslipidemia, 1053 (8.8%) subjects died during the follow-up period. Of the dyslipidemia patients earning a middle-class income, the adjusted HR in less affluent neighborhoods was higher than that in the more affluent neighborhoods compared to the reference category of high individual SES in more affluent neighborhoods (less affluent; hazard ratio (HR) = 1.64, 95% confidence interval (CI): 1.35-1.99 vs. more affluent; HR = 1.48, 95% CI: 1.20-1.81, respectively). We obtained consistent results in patients with lower income, wherein the adjusted HR in less affluent neighborhoods was higher than that in more affluent neighborhoods (less affluent; HR = 1.52, 95% CI: 1.16-1.97 vs. more affluent; HR = 1.41, 95% CI: 1.04-1.92, respectively). CONCLUSION: Living in a less affluent neighborhood contributes to higher mortality among dyslipidemia patients. The individual- and neighborhood-level variables cumulatively affect individuals such that the most at-risk individuals include those having both individual- and neighborhood-level risk factors. These findings raise important clinical and public health concerns and indicate that neighborhood SES approaches should be essentially considered in health-care policies similar to individual SES. PMID- 26895649 TI - Scientists forge ahead with human-animal chimaeras. PMID- 26895650 TI - Hypoxic pulmonary hypertension in chronic lung diseases: novel vasoconstrictor pathways. AB - Pulmonary hypertension is a well recognised complication of chronic hypoxic lung diseases, which are among the most common causes of death and disability worldwide. Development of pulmonary hypertension independently predicts reduced life expectancy. In chronic obstructive pulmonary disease, long-term oxygen therapy ameliorates pulmonary hypertension and greatly improves survival, although the correction of alveolar hypoxia and pulmonary hypertension is only partial. Advances in understanding of the regulation of vascular smooth muscle tone show that chronic vasoconstriction plays a more important part in the pathogenesis of hypoxic pulmonary hypertension than previously thought, and that structural vascular changes contribute less. Trials of existing vasodilators show that pulmonary hypertension can be ameliorated and systemic oxygen delivery improved in carefully selected patients, although systemic hypotensive effects limit the doses used. Vasoconstrictor pathways that are selective for the pulmonary circulation can be blocked to reduce hypoxic pulmonary hypertension without causing systemic hypotension, and thus provide potential targets for novel therapeutic strategies. PMID- 26895651 TI - Steroids reduce respiratory problems in late preterm infants. PMID- 26895653 TI - Light therapy and chronobiology in critical illness. PMID- 26895652 TI - Dynamic light application therapy to reduce the incidence and duration of delirium in intensive-care patients: a randomised controlled trial. AB - BACKGROUND: Disturbed circadian rhythm is a potentially modifiable cause of delirium among patients in intensive-care units (ICUs). Bright-light therapy in the daytime can realign circadian rhythm and reduce the incidence of delirium. We investigated whether a high-intensity dynamic light application (DLA) would reduce ICU-acquired delirium. METHODS: This was a randomised, controlled, single centre trial of medical and surgical patients admitted to the ICU of a teaching hospital in the Netherlands. Patients older than 18 years, expected to stay in the ICU longer than 24 h and who could be assessed for delirium were randomised to DLA or normal lighting (control), according to a computer-generated schedule. The DLA was administered through ceiling-mounted fluorescent tubes that delivered bluish-white light up to 1700 lux between 0900 h and 1600 h, except for 1130-1330 h, when the light was dimmed to 300 lux. The light could only be turned off centrally by investigators. Control light levels were 300 lux and lights could be turned on and off from inside the room. The primary endpoint was the cumulative incidence of ICU-acquired delirium. Analyses were by intention to treat and per protocol. The study was terminated prematurely after an interim analysis for futility. This study is registered with Clinicaltrials.gov, number NCT01274819. FINDINGS: Between July 1, 2011, and Sept 9, 2013, 734 patients were enrolled, 361 in the DLA group and 373 in the control group. Delirium occurred in 137 (38%) of 361 DLA patients and 123 (33%) of 373 control patients (odds ratio 1.24, 95% CI 0.92-1.68, p=0.16). No adverse events were noted in patients or staff. INTERPRETATION: DLA as a single intervention does not reduce the cumulative incidence of delirium. Bright-light therapy should be assessed as part of a multicomponent strategy. FUNDING: None. PMID- 26895654 TI - Resisting the use of antibiotics for viral infections. PMID- 26895655 TI - Australian law could silence critics of refugee health. PMID- 26895657 TI - A new GLP-1 analogue with prolonged glucose-lowering activity in vivo via backbone-based modification at the N-terminus. AB - Glucagon-like peptide-1 (GLP-1) is an endogenous insulinotropic hormone with wonderful glucose-lowering activity. However, its clinical use in type II diabetes is limited due to its rapid degradation at the N-terminus by dipeptidyl peptidase IV (DPP-IV). Among the N-terminal modifications of GLP-1, backbone based modification was rarely reported. Herein, we employed two backbone-based strategies to modify the N-terminus of tGLP-1. Firstly, the amide N-methylated analogues 2-6 were designed and synthesized to make a full screening of the N terminal amide bonds, and the loss of GLP-1 receptor (GLP-1R) activation indicated the importance of amide H-bonds. Secondly, with retaining the N terminal amide H-bonds, the beta-peptide replacement strategy was used and analogues 7-13 were synthesized. By two rounds of screening, analogue 10 was identified. Analogue 10 greatly improved the DPP-IV resistance with maintaining good GLP-1R activation in vitro, and showed approximately a 4-fold prolonged blood glucose-lowering activity in vivo in comparison with tGLP-1. This modification strategy will benefit the development of GLP-1-based anti-diabetic drugs. PMID- 26895656 TI - Local anaesthesia versus spinal anaesthesia in inguinal hernia repair: A systematic review and meta-analysis. AB - BACKGROUND: Inguinal hernias are a significant cause of morbidity. The purpose of this systematic review and meta-analysis is to determine the totality of evidence regarding the effectiveness of local anaesthesia when compared to spinal anaesthesia in individuals undergoing open inguinal hernia repair. METHODS: A systematic literature search was conducted. Inclusion criteria were randomised controlled trials (RCTs) comparing spinal and local anaesthesia on clinical and self-reported outcomes, in patients undergoing open inguinal hernia repairs. The methodological quality was assessed using the Cochrane risk of bias tool. The mode of analysis used was the difference in outcomes between the groups post surgery and at follow-up time points. Statistical heterogeneity was assessed using the I2 statistic. RESULTS: Ten original RCTs were included, with a total of 1379 patients. There was no significant difference in operative time between the groups [Random Effects Model, MD -0.70 min (95% CI, -5.80 to 4.40 min), p = 0.79, I2 = 84%]. Patients in the local anaesthetic group experienced significantly less pain than those in the spinal group [Fixed Effects Model, SMD -0.63 (95% CI, 0.81 to -0.46), p < 0.01, I2 = 49%], lower rates of urinary retention [FEM, RR 0.03 (95% CI 0.01-0.08), p < 0.01, I2 = 0%], decreased rates of anaesthetic failure [FEM, OR 0.17 (95% CI 0.06-0.45), p < 0.01, I2 = 0%], and increased satisfaction with the anaesthetic [FEM, OR 3.40 (95% CI 2.09-5.52), p < 0.01, I2 = 0%]. The methodological quality of studies was variable. CONCLUSION: Our findings support the use of local anaesthetic in adult patients undergoing open repair for a primary inguinal hernia. PMID- 26895658 TI - Candida albicans beta-1,2 mannosyl transferase Bmt3: Preparation and evaluation of a beta (1,2), alpha (1,2)-tetramannosyl fluorescent substrate. AB - We describe for the first time the chemical synthesis of a tetramannoside, containing both alpha (1->2) and beta (1->2) linkages. Dodecylthio (lauryl) glycosides were prepared from odorless dodecyl thiol and used as donors for the glycosylation steps. This tetramannoside, was coupled to a mantyl group, and revealed to be a perfect substrate of beta-mannosyltransferase Bmt3, confirming the proposed specificity and allowing the preparation of a pentamannoside sequence (beta Man (1,2) beta Man (1,2) alpha Man (1,2) alpha Man (1,2) alpha Man) usable as a novel substrate for further elongation studies. PMID- 26895659 TI - Nutritional therapy for nonalcoholic fatty liver disease. AB - Following the epidemics of obesity, nonalcoholic fatty liver disease (NAFLD) has become the leading cause of liver disease in western countries. NAFLD is the hepatic manifestation of metabolic syndrome and may progress to cirrhosis and hepatocellular carcinoma. To date, there are no approved drugs for the treatment of NAFLD, and the main clinical recommendation is lifestyle modification, including increase of physical activity and the adoption of a healthy eating behavior. In this regard, studies aimed to elucidate the effect of dietary interventions and the mechanisms of action of specific food bioactives are urgently needed. The present review tries to summarize the most recent data evidencing the effects of nutrients and dietary bioactive compounds intake (i.e., long-chain PUFA, Vitamin E, Vitamin D, minerals and polyphenols) on the modulation of molecular mechanisms leading to fat accumulation, oxidative stress, inflammation and liver fibrosis in NAFLD patients. PMID- 26895661 TI - Astaxanthin prevents and reverses the activation of mouse primary hepatic stellate cells. AB - Activation of hepatic stellate cells (HSCs) is a critical step that leads to the development of liver fibrosis. We showed that astaxanthin (ASTX), a xanthophyll carotenoid, displays antifibrogenic effects in LX-2 cells, a human HSC cell line. In this study, we further determined the effect of ASTX on HSC activation and inactivation using primary HSCs from C57BL/6J mice. Quiescent and activated HSCs were incubated with ASTX (25MUM) at different stages of activation. ASTX prevented the activation of quiescent HSCs, as evidenced by the presence of intracellular lipid droplets and reduction of alpha-smooth muscle actin, an HSC activation marker. Also, ASTX reverted activated HSCs to a quiescent phenotype with the reappearance of lipid droplets with a concomitant increase in lecithin retinol acyltransferase mRNA. Cellular accumulation of reactive oxygen species was significantly reduced by ASTX, which was attributable to a decrease in NADPH oxidase 2 expression. The antifibrogenic effect of ASTX was independent of nuclear erythroid 2-related factor 2 as it was observed in HSCs from wild-type and Nrf2(-/-) mice. In conclusion, ASTX inhibits HSC activation and reverts activated HSCs to a quiescent state. Further investigation is warranted to determine if ASTX effectively prevents the development of liver fibrosis. PMID- 26895660 TI - Isocaloric manipulation of macronutrients within a high-carbohydrate/moderate-fat diet induces unique effects on hepatic lipogenesis, steatosis and liver injury. AB - Diets containing excess carbohydrate and fat promote hepatic steatosis and steatohepatitis in mice. Little is known, however, about the impact of specific carbohydrate/fat combinations on liver outcome. This study was designed to determine whether high-energy diets with identical caloric density but different carbohydrate and fat composition have unique effects on the liver. Four experimental diets were formulated with 60%kcal carbohydrate and 20%kcal fat, each in nearly pure form from a single source: starch-oleate, starch-palmitate, sucrose-oleate and sucrose-palmitate. The diets were fed to mice for 3 or 12 weeks for analysis of lipid metabolism and liver injury. All mice developed hepatic steatosis over 12 weeks, but mice fed the sucrose-palmitate diet accumulated more hepatic lipid than those in the other three experimental groups. The exaggerated lipid accumulation in sucrose-palmitate-fed mice was attributable to a disproportionate rise in hepatic de novo lipogenesis. These mice accrued more hepatic palmitate and exhibited more evidence of liver injury than any of the other experimental groups. Interestingly, lipogenic gene expression in mice fed the custom diets did not correlate with actual de novo lipogenesis. In addition, de novo lipogenesis rose in all mice between 3 and 12 weeks, without feedback inhibition from hepatic steatosis. The pairing of simple sugar (sucrose) and saturated fat (palmitate) in a high-carbohydrate/moderate-fat diet induces more de novo lipogenesis and liver injury than other carbohydrate/fat combinations. Diet-induced liver injury correlates positively with hepatic de novo lipogenesis and is not predictable by isolated analysis of lipogenic gene expression. PMID- 26895662 TI - Effects of folylpolyglutamate synthase modulation on global and gene-specific DNA methylation and gene expression in human colon and breast cancer cells. AB - Folylpolyglutamate synthase (FPGS) plays a critical role in intracellular folate homeostasis. FPGS-induced polyglutamylated folates are better substrates for several enzymes involved in the generation of S-adenosylmethionine, the primary methyl group donor, and hence FPGS modulation may affect DNA methylation. DNA methylation is an important epigenetic determinant in gene expression and aberrant DNA methylation is mechanistically linked cancer development. We investigated whether FPGS modulation would affect global and gene-specific promoter DNA methylation with consequent functional effects on gene expression profiles in HCT116 colon and MDA-MB-435 breast cancer cells. Although FPGS modulation altered global DNA methylation and DNA methyltransferases (DNMT) activity, the effects of FPGS modulation on global DNA methylation and DNMT activity could not be solely explained by intracellular folate concentrations and content of long-chain folylpolyglutamates, and it may be cell-specific. FPGS modulation influenced differential gene expression and promoter cytosine-guanine dinucleotide sequences (CpG) DNA methylation involved in cellular development, cell cycle, cell death and molecular transport. Some of the altered gene expression was associated with promoter CpG DNA methylation changes. In both the FPGS-overexpressed HCT116 and MDA-MB-435 cell lines, we identified several differentially expressed genes involved in folate biosynthesis and one-carbon metabolism, which might in part have contributed to the observed increased efficacy of 5-fluorouracil in response to FPGS overexpression. Our data suggest that FPGS modulation affects global and promoter CpG DNA methylation and expression of several genes involved in important biological pathways. The potential role of FPGS modulation in DNA methylation and its associated downstream functional effects warrants further studies. PMID- 26895663 TI - Daily sesame oil supplement attenuates joint pain by inhibiting muscular oxidative stress in osteoarthritis rat model. AB - Osteoarthritis (OA) is the most common form of arthritis, affecting approximately 15% of the population. The aim of this study was to evaluate the efficacy of sesame oil in controlling OA pain in rats. Rat joint pain was induced by medial meniscal transection in Sprague-Dawley rats and assessed by using hindlimb weight distribution method. Muscular oxidative stress was assessed by determining lipid peroxidation, reactive oxygen species and circulating antioxidants. Sesame oil significantly decreased joint pain compared with positive control group in a dose dependent manner. Sesame oil decreased lipid peroxidation in muscle but not in serum. Further, sesame oil significantly decreased muscular superoxide anion and peroxynitrite generations but increased muscular glutathione and glutathione peroxidase levels. Further, sesame oil significantly increased nuclear factor erythroid-2-related factor (Nrf2) expression compared with positive control group. We concluded that daily sesame oil supplement may attenuate early joint pain by inhibiting Nrf2-associated muscular oxidative stress in OA rat model. PMID- 26895664 TI - Early postnatal feed restriction reduces liver connective tissue levels and affects H3K9 acetylation state of regulated genes associated with protein metabolism in low birth weight pigs. AB - Intrauterine growth retardation is associated with metabolic consequences in adulthood. Since our previous data indicate birth weight-dependent effects of feed restriction (R) on protein degradation processes in the liver, it should be investigated whether effects on connective tissue turnover are obvious and could be explained by global changes of histone H3K9me3 and H3K9ac states in regulated genes. For this purpose, female littermate pigs with low (U) or normal (N) birth weight were subjected to 3-week R (60% of ad libitum fed controls) with subsequent refeeding (REF) for further 5 weeks. The 3-week R-period induced a significant reduction of connective tissue area by 43% in the liver of U animals at 98 d of age, which was not found in age-matched N animals. Of note, after REF at 131 d of age, in previously feed-restricted U animals (UR), the percentage of mean connective tissue was only 53% of ad libitum fed controls (UK), indicating a persistent effect. In U animals, R induced H3K9 acetylation of regulated genes (e.g. XBP1, ERLEC1, GALNT2, PTRH2), which were inter alia associated with protein metabolism. In contrast, REF was mostly accompanied by deacetylation in U and N animals. Thus, our epigenetic data may give a first explanation for the observed birth weight-dependent differences in this connective tissue phenotype. PMID- 26895665 TI - Liver-specific deletion of the signal transducer and activator of transcription 5 gene aggravates fatty liver in response to a high-fat diet in mice. AB - Growth hormone (GH) signal is mediated by signal transducer and activator of transcription 5 (STAT5), which controls hepatic lipid metabolism. Nonalcoholic fatty liver disease (NAFLD) is clinically associated with a deficiency in GH. This study was performed to understand the role of local STAT5 signaling on hepatic lipid and glucose metabolism utilizing liver-specific STAT5 gene deletion (STAT5 LKO) mice under both normal diet and high-fat diet (HFD) feeding conditions. STAT5 LKO induced hepatic steatosis under HFD feeding, while this change was not observed in mice on normal diet. STAT5 LKO caused hyperglycemia, hyperinsulinemia, hyperleptinemia and elevated free fatty acid and cholesterol concentrations under HFD feeding but induced only hyperglycemia on normal diet. At the molecular level, STAT5 LKO up-regulated the expression of genes involved in lipid uptake (CD36), very low-density lipoprotein receptor (VLDLR), lipogenic stearoyl-CoA desaturase and adipogenic peroxisome proliferator-activated receptor gamma, in both diet groups. In response to HFD feeding, further increases in CD36 and VLDLR expression were found in STAT5 LKO mice. In conclusion, our study suggests that low STAT5 signaling on normal diet predisposes STAT5 LKO mice to early development of fatty liver by hyperglycemia and activation of lipid uptake and adipogenesis. A deficiency in STAT5 signaling under HFD feeding deregulates hepatic and body glucose and lipid metabolism, leading to the development of hepatic steatosis. Our study indicates that low STAT5 signaling, due to low GH secretion, may increase a chance for NAFLD development in elderly people. PMID- 26895666 TI - Dysregulated expression of arginine metabolic enzymes in human intestinal tissues of necrotizing enterocolitis and response of CaCO2 cells to bacterial components. AB - The small intestine is the exclusive site of arginine synthesis in neonates. Low levels of circulating arginine have been associated with the occurrence of necrotizing enterocolitis (NEC) but the mechanism of arginine dysregulation has not been fully elucidated. We aimed to investigate (i) expressional changes of arginine synthesizing and catabolic enzymes in human intestinal tissues of NEC, spontaneous intestinal perforation (SIP) and noninflammatory surgical conditions (Surg-CTL) and to investigate the (ii) mechanisms of arginine dysregulation and enterocyte proliferation upon stimulation by bacterial components, arginine depletion, ARG1 overexpression and nitric oxide (NO) supplementation. Our results showed that expressions of arginine synthesizing enzymes ALDH18A1, ASL, ASS1, CPS1, GLS, OAT and PRODH were significantly decreased in NEC compared with Surg CTL or SIP tissues. Catabolic enzyme ARG1 was increased (>100-fold) in NEC tissues and histologically demonstrated to be expressed by infiltrating neutrophils. No change in arginine metabolic enzymes was observed between SIP and Surg-CTL tissues. In CaCO2 cells, arginine metabolic enzymes were differentially dysregulated by lipopolysaccharide or lipoteichoic acid. Depletion of arginine reduced cell proliferation and this phenomenon could be partially rescued by NO. Overexpression of ARG1 also reduced enterocyte proliferation. We provided the first expressional profile of arginine metabolic enzymes at the tissue level of NEC. Our findings suggested that arginine homeostasis was severely disturbed and could be triggered by inflammatory responses of enterocytes and infiltrating neutrophils as well as bacterial components. Such reactions could reduce arginine and NO, resulting in mucosal damage. The benefit of arginine supplementation for NEC prophylaxis merits further clinical evaluation. PMID- 26895669 TI - Age related differences in the plasma kinetics of flavanols in rats. AB - Dietary flavanols produce beneficial health effects; once absorbed, they are recognized as xenobiotics and undergo Phase-II enzymatic detoxification. However, flavanols with a degree of polymerization greater than 2 reach the colon, where they are subjected to microbial metabolism and can be further absorbed and undergo Phase-II reactions. In this sense, flavanols' health-promoting properties are mainly attributed to their metabolic products. Several age-related physiological changes have been evidenced, and it is known that flavanols' bioavailability is affected by internal factors. Therefore, this study aimed to elucidate whether animals of different ages, specifically young and adult rats, exhibit differences in their flavanol metabolism and plasma bioavailability. To accomplish this, an acute dose of a grape seed polyphenol extract was administered to male rats; after 2, 4, 7, 24 and 48 h, flavanols and their Phase II and microbial metabolites were quantified by HPLC-ESI-MS/MS in plasma. The results indicated important age-related quantitative differences in plasma flavanol metabolites. Interestingly, adult rats presented a remarkable reduction in flavanol absorption and Phase-II flavanol metabolism. Consequently, microbial derived flavanol metabolism is triggered by higher flavanol affluence in the colonic tract. Furthermore, young rats presented a faster metabolic profile than adult rats. Hence, our results indicate that the physiological bioactivities of flavanols may depend on age. PMID- 26895668 TI - Allicin inhibits lymphangiogenesis through suppressing activation of vascular endothelial growth factor (VEGF) receptor. AB - Allicin, the most abundant organosulfur compound in freshly crushed garlic tissues, has been shown to have various health-promoting effects, including anticancer actions. A better understanding of the effects and mechanisms of allicin on tumorigenesis could facilitate development of allicin or garlic products for cancer prevention. Here we found that allicin inhibited lymphangiogenesis, which is a critical cellular process implicated in tumor metastasis. In primary human lymphatic endothelial cells, allicin at 10 MUM inhibited capillary-like tube formation and cell migration, and it suppressed phosphorylation of vascular endothelial growth factor receptor 2 and focal adhesion kinase. Using a Matrigel plug assay in mice, addition of 10 MUg allicin in Matrigel plug inhibited 40-50% of vascular endothelial growth factor-C-induced infiltration of lymphatic endothelial cells and leukocytes. S Allylmercaptoglutathione, a major cellular metabolite of allicin, had no effect on lymphangiogenic responses in lymphatic endothelial cells. Together, these results demonstrate the antilymphangiogenic effect of allicin in vitro and in vivo, suggesting a novel mechanism for the health-promoting effects of garlic compounds. PMID- 26895667 TI - In utero exposure of rats to high-fat diets perturbs gene expression profiles and cancer susceptibility of prepubertal mammary glands. AB - Human studies suggest that high-fat diets (HFDs) increase the risk of breast cancer. The 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis rat model is commonly used to evaluate the effects of lifestyle factors such as HFD on mammary tumor risk. Past studies focused primarily on the effects of continuous maternal exposure on the risk of offspring at the end of puberty (PND50). We assessed the effects of prenatal HFD exposure on cancer susceptibility in prepubertal mammary glands and identified key gene networks associated with such disruption. During pregnancy, dams were fed AIN-93G-based diets with isocaloric high olive oil, butterfat or safflower oil. The control group received AIN-93G. Female offspring were treated with DMBA on PND21. However, a significant increase in tumor volume and a trend of shortened tumor latency were observed in rats with HFD exposure against the controls (P=.048 and P=.067, respectively). Large-volume tumors harbored carcinoma in situ. Transcriptome profiling identified 43 differentially expressed genes in the mammary glands of the HFBUTTER group as compared with control. Rapid hormone signaling was the most dysregulated pathway. The diet also induced aberrant expression of Dnmt3a, Mbd1 and Mbd3, consistent with potential epigenetic disruption. Collectively, these findings provide the first evidence supporting susceptibility of prepubertal mammary glands to DMBA-induced tumorigenesis that can be modulated by dietary fat that involves aberrant gene expression and likely epigenetic dysregulation. PMID- 26895670 TI - Docosahexaenoic acid confers analgesic effects after median nerve injury via inhibition of c-Jun N-terminal kinase activation in microglia. AB - The c-Jun N-terminal kinase (JNK) in the central nervous system plays a critical role in the processing of neuropathic pain. Docosahexaenoic acid (DHA), a predominant omega-3 polyunsaturated fatty acid in the central nervous system, has a neuroprotective efficacy. In this study, we examined the relationships between JNK activation in the cuneate nucleus (CN) and behavioral hypersensitivity after chronic constriction injury (CCI) of the median nerve. We further investigated the effects of DHA administration on JNK activation and development of hypersensitivity. Using immunohistochemistry and immunoblotting, low levels of phosphorylated JNK (p-JNK) were detected in the CN of sham-operated rats. As early as 1 day after CCI, p-JNK levels in the ipsilateral CN were significantly increased and peaked at 7 days. Double-immunofluorescence labeling with cell specific markers showed that p-JNK immunoreactive cells coexpressed OX-42, a microglia activation marker, suggesting the expression of p-JNK in the microglia. Microinjection of SP600125, a JNK inhibitor, into the CN 1 day after CCI attenuated injury-induced behavioral hypersensitivity in a dose-dependent manner. Furthermore, animals received intravenous injection of DHA at doses of 100, 250 or 500 nmol/kg 30 min after median nerve CCI. DHA treatment decreased p-JNK and OX-42 levels, diminished the release of proinflammatory cytokines and improved behavioral hypersensitivity following CCI. In conclusion, median nerve injury induced microglial JNK activation in the CN modulated development of behavioral hypersensitivity. DHA has analgesic effects on neuropathic pain, at least in part, by means of suppressing a microglia-mediated inflammatory response through the inhibition of JNK signaling pathway. PMID- 26895671 TI - Beneficial effects of quercetin-iron complexes on serum and tissue lipids and redox status in obese rats. AB - Obesity is characterized by iron deficiency, carbohydrate and fat alterations as well as oxidative stress. Iron status monitoring is recommended because of the conventional oral iron preparations that frequently exacerbate the already present oxidative stress. Iron complexation by natural antioxidants can be exploited. We herein investigated the metabolic effects of quercetin (25 mg/kg/day), iron (2.5 mg Fe/kg/day) or quercetin-iron complexes (molar ratio 5:1; 25 mg/2.5 mg/kg/day) in animal models of obesity. Our results emphasized that obese rats displayed metabolic alterations that were worsened by iron supplementation. In contrast, quercetin used alone or as iron complex clearly prevented adipose fat accumulation and alleviated the hyperglycemia, hyperlipidemia, liver steatosis and oxidative stress. In addition, it induced a modulation of lipase activities in obese rats. Interestingly, quercetin-iron complexes showed enhanced beneficial effects such as a corrected iron deficiency in obese rats when compared to quercetin alone. In conclusion, antianemic, hypoglycemic, hypolipidemic and antioxidative effects of the quercetin-iron complexes shed a light on their beneficial use against obesity-related metabolic alterations. PMID- 26895672 TI - Induction of regulatory T cells in Th1-/Th17-driven experimental autoimmune encephalomyelitis by zinc administration. AB - The essential trace element zinc is indispensable for proper immune function as zinc deficiency accompanies immune defects and dysregulations like allergies, autoimmunity and an increased presence of transplant rejection. This point to the importance of the physiological and dietary control of zinc levels for a functioning immune system. This study investigates the capacity of zinc to induce immune tolerance. The beneficial impact of physiological zinc supplementation of 6 MUg/day (0.3mg/kg body weight) or 30 MUg/day (1.5mg/kg body weight) on murine experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis with a Th1/Th17 (Th, T helper) cell-dominated immunopathogenesis, was analyzed. Zinc administration diminished EAE scores in C57BL/6 mice in vivo (P<.05), reduced Th17 RORgammaT(+) cells (P<.05) and significantly increased inducible iTreg cells (P<.05). While Th17 cells decreased systemically, iTreg cells accumulated in the central nervous system. Cumulatively, zinc supplementation seems to be capable to induce tolerance in unwanted immune reactions by increasing iTreg cells. This makes zinc a promising future tool for treating autoimmune diseases without suppressing the immune system. PMID- 26895673 TI - Meningococcal carriage rates in healthy individuals in Japan determined using Loop-Mediated Isothermal Amplification and oral throat wash specimens. AB - The detailed epidemiology of meningococcal diseases in Japan has yet to be determined and, moreover, the healthy carriage rate is also unknown. In this study, to obtain insight into the carriage rate of Neisseria meningitidis in healthy individuals in Japan, we developed a new method to detect the N. meningitidis-specific ctrB gene, one of the genes encoding enzymes for capsule synthesis, by Loop-Mediated Isothermal Amplification (LAMP) and examined the meningococcal carriage rate by using self-collected oral throat wash specimens from 836 students at a university. Examination by LAMP showed that 7 out of 836 samples were positive for N. meningitidis DNA, and the results were also verified by the nested PCR method for the meningococcus specific ggt gene. The N. meningitidis carriage rate in healthy individuals was estimated to be 0.84%. Moreover, we further confirmed by the nested-PCR-based serogroup typing method that 5 of the positive samples belonged to serogroup Y, 1 belonged to group B and 1 was unidentifiable. Considering the epidemiology for meningococcal diseases in Japan, the carriage rate and the serogroup profile seem to be consistent with low incidence of meningococcal diseases and serogroup distribution of clinical meningococcal isolates in Japan, respectively. PMID- 26895674 TI - Comparative evaluation of Amblyomma ovale ticks infected and noninfected by Rickettsia sp. strain Atlantic rainforest, the agent of an emerging rickettsiosis in Brazil. AB - In 2010, a novel spotted fever group rickettsiosis was reported in the Atlantic rainforest coast of Brazil. The etiological agent was identified as Rickettsia sp. strain Atlantic rainforest, and the tick Amblyomma ovale was incriminated as the presumed vector. The present study evaluated under laboratory conditions four colonies of A. ovale: two started from engorged females that were naturally infected by Rickettsia sp. strain Atlantic rainforest (designated as infected groups); the two others started from noninfected females (designated as control groups). All colonies were reared in parallel from F0 engorged female to F2 unfed nymphs. Tick-naive vesper mice (Calomys callosus) or domestic rabbits were used for feeding of each tick stage. Rickettsia sp. strain Atlantic rainforest was preserved by transstadial maintenance and transovarial transmission in A. ovale ticks for at least 2 generations (from F0 females to F2 nymphs), because nearly 100% of the tested larvae, nymphs, and adults from the infected groups were shown by PCR to contain rickettsial DNA. All vesper mice and rabbits infested by larvae and nymphs, and 50% of the rabbits infested by adults from the infected groups seroconverted, indicating that these tick stages were vector competent for Rickettsia sp. strain Atlantic rainforest. Expressive differences in mortality rates and reproductive performance were observed between engorged females from the infected and control groups, as indicated by 75.0% and 97.1% oviposition success, respectively, and significantly lower egg mass weight, conversion efficiency index, and percentage of egg hatching for the infected groups. Our results indicate that A. ovale can act as a natural reservoir for Rickettsia sp. strain Atlantic rainforest. However, due to deleterious effect caused by this rickettsial agent on engorged females, amplifier vertebrate hosts might be necessary for persistent perpetuation of Rickettsia sp. strain Atlantic rainforest in A. ovale under natural conditions. PMID- 26895676 TI - Is this laparoscopic technique study the perfect surgical trial? PMID- 26895675 TI - Closure of mesenteric defects in laparoscopic gastric bypass: a multicentre, randomised, parallel, open-label trial. AB - BACKGROUND: Small bowel obstruction due to internal hernia is a common and potentially serious complication after laparoscopic gastric bypass surgery. Whether closure of surgically created mesenteric defects might reduce the incidence is unknown, so we did a large randomised trial to investigate. METHOD: This study was a multicentre, randomised trial with a two-arm, parallel design done at 12 centres for bariatric surgery in Sweden. Patients planned for laparoscopic gastric bypass surgery at any of the participating centres were offered inclusion. During the operation, a concealed envelope was opened and the patient was randomly assigned to either closure of mesenteric defects beneath the jejunojejunostomy and at Petersen's space or non-closure. After surgery, assignment was open label. The main outcomes were reoperation for small bowel obstruction and severe postoperative complications. Outcome data and safety were analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01137201. FINDINGS: Between May 1, 2010, and Nov 14, 2011, 2507 patients were recruited to the study and randomly assigned to closure of the mesenteric defects (n=1259) or non-closure (n=1248). 2503 (99.8%) patients had follow-up for severe postoperative complications at day 30 and 2482 (99.0%) patients had follow-up for reoperation due to small bowel obstruction at 25 months. At 3 years after surgery, the cumulative incidence of reoperation because of small bowel obstruction was significantly reduced in the closure group (cumulative probability 0.055 for closure vs 0.102 for non-closure, hazard ratio 0.56, 95% CI 0.41-0.76, p=0.0002). Closure of mesenteric defects increased the risk for severe postoperative complications (54 [4.3%] for closure vs 35 [2.8%] for non-closure, odds ratio 1.55, 95% CI 1.01-2.39, p=0.044), mainly because of kinking of the jejunojejunostomy. INTERPRETATION: The results of our study support the routine closure of the mesenteric defects in laparoscopic gastric bypass surgery. However, closure of the mesenteric defects might be associated with increased risk of early small bowel obstruction caused by kinking of the jejunojejunostomy. FUNDING: Orebro County Council, Stockholm City Council, and the Erling-Persson Family Foundation. PMID- 26895678 TI - Pancreatic Pseudocysts: Advances in Endoscopic Management. AB - Endoscopic drainage is the first-line therapy in the management of pancreatic pseudocysts. Before endoscopic drainage, clinicians should exclude the presence of pancreatic cystic neoplasms and avoid drainage of immature peripancreatic fluid collections or pseudoaneurysms. The indication for endoscopic drainage is not dependent on absolute cyst size alone, but on the presence of attributable signs or symptoms. Endoscopic management should be performed as part of a multidisciplinary approach in close cooperation with surgeons and interventional radiologists. Drainage may be performed either via a transpapillary approach or a transmural approach; additionally, endoscopic necrosectomy may be performed for patients with walled-off necrosis. PMID- 26895677 TI - Advances in Management of Acute Pancreatitis. AB - This article reviews advances in the management of acute pancreatitis. Medical treatment has been primarily supportive for this diagnosis, and despite extensive research efforts, there are no pharmacologic therapies that improve prognosis. The current mainstay of management, notwithstanding the ongoing debate regarding the volume, fluid type, and rate of administration, is aggressive intravenous fluid resuscitation. Although antibiotics were used consistently for prophylaxis in severe acute pancreatitis to prevent infection, they are no longer used unless infection is documented. Enteral nutrition, especially in patients with severe acute pancreatitis, is considered a cornerstone in management of this disease. PMID- 26895679 TI - Autoimmune Pancreatitis: An Update on Diagnosis and Management. AB - There is an evolving understanding that autoimmune pancreatitis (AIP) is an immunoglobulin (Ig) G4 systemic disease. It can manifest as primarily a pancreatic disorder or in association with other disorders of presumed autoimmune cause. Classic clinical characteristics include obstructive jaundice, abdominal pain, and acute pancreatitis. Thus, AIP can be difficult to distinguish from pancreatic malignancy. However, AIP may respond to therapy with corticosteroids, and has a strong association with other immune mediated diseases. Although primarily a pathologic diagnosis, attempts have been made to reliably diagnose AIP clinically. AIP can be classified as either type 1 or type 2. PMID- 26895680 TI - The Role of Endoscopic Retrograde Cholangiopancreatography in Management of Pancreatic Diseases. AB - Endoscopic retrograde cholangiopancreatography is an effective platform for a variety of therapies in the management of benign and malignant disease of the pancreas. Over the last 50 years, endotherapy has evolved into the first-line therapy in the majority of acute and chronic inflammatory diseases of the pancreas. As this field advances, it is important that gastroenterologists maintain an adequate knowledge of procedure indication, maintain sufficient procedure volume to handle complex pancreatic endotherapy, and understand alternate approaches to pancreatic diseases including medical management, therapy guided by endoscopic ultrasonography, and surgical options. PMID- 26895681 TI - Pancreatic Cystic Neoplasms: An Update. AB - The incidence of pancreatic cystic neoplasms is rising, in part from detection through the increasing use of high-resolution cross-sectional imaging techniques. Initial diagnosis is generally based on imaging characteristics identified on computed tomography and/or MRI. Endoscopic ultrasound provides further imaging characterization and also enables fluid aspiration and analysis to additionally aid differentiation. The general approach to these lesions includes surgical intervention and/or surveillance imaging. Taking into account diverse presentations, varying malignant potential, and the uncertain natural history of some of these lesions, an evidence-based approach is limited. This article discusses recent updates in the diagnosis and management of cystic neoplasms of the pancreas. PMID- 26895682 TI - Islet Cell Tumors of the Pancreas. AB - Islet cell tumors of the pancreas, also known as pancreatic neuroendocrine tumors, constitute less than 5% of pancreatic tumors, and 7% of all neuroendocrine tumors. Most are non-functional, and patients often present with metastatic disease. Functional tumors present with distinct clinical syndromes. Accurate staging is critical as surgery is both the cornerstone of treatment, and the only hope for cure. Medical management involves treating the manifestations of hormonal excess, and using somatastatin analogues when appropriate. Systemic chemotherapy, targeted molecular therapy, and peptide receptor radiotherapy may be used for refractory disease in lieu of or as an adjunct to surgery. PMID- 26895683 TI - Imaging of the Pancreas. AB - The evaluation of pancreatic lesions, from solid pancreatic masses to pancreatic cysts, remains a clinical challenge. Although cross-sectional imaging remains the cornerstone of the initial evaluation of an indeterminate pancreatic lesion, advances in imaging with the advent of endoscopic ultrasound scan, elastography, contrast-enhanced endoscopic ultrasound scan, and probe-based confocal laser endomicroscopy have allowed us to visualize the pancreas in even higher resolution and diagnose premalignant and malignant lesions of the pancreas with improved accuracy. This report reviews the range of imaging tools currently available to evaluate pancreatic lesions, from solid tumors to pancreatic cysts. PMID- 26895684 TI - Screening for Pancreatic Cancer in High-risk Populations. AB - Pancreatic adenocarcinoma is a leading cause of cancer death. Few patients are candidates for curative resection due to the late stage at diagnosis. While most pancreatic adenocarcinomas are sporadic, approximately 10% have an underlying hereditary basis. Known genetic syndromes account for only 20% of the familial clustering of pancreatic cancer cases. The majority are due to non-syndromic aggregation of pancreatic cancer cases or familial pancreatic cancer. Screening aims to identify high-risk lesions amenable to surgical resection. However, the optimal interval for screening and the management of pancreatic cancer precursor lesions detected on imaging are controversial. PMID- 26895685 TI - Advances in Surgical Management of Pancreatic Diseases. AB - The surgical management of pancreatic diseases is rapidly evolving, encompassing advances in evidence-driven selection of patients amenable for surgical therapy, preoperative risk stratification, refinements in the technical conduct of pancreatic operations, and quantification of postoperative morbidity. These advances have resulted in dramatic reductions in mortality following pancreatic surgery, particularly at high-volume pancreatic centers. Surgical decision making is complex, and requires an intimate understanding of disease pathobiology, host physiology, technical considerations, and evolving trends. This article highlights key developments in the contemporary surgical management of pancreatic diseases. PMID- 26895686 TI - Pancreas Transplantation in the Modern Era. AB - The field of pancreas transplantation has evolved from an experimental procedure in the 1980s to become a routine transplant in the modern era. With short- and long-term outcomes continuing to improve and the significant mortality, quality of-life, and end-organ disease benefits, pancreas transplantation should be offered to more patients. In this article, we review current indications, patient selection, surgical considerations, complications, and outcomes in the modern era of pancreas transplantation. PMID- 26895687 TI - Advances in Management of Pancreatic Diseases. PMID- 26895688 TI - Pathologic fracture a poor prognostic factor in osteosarcoma: Misleading conclusions from meta-analyses? AB - AIM: Recently published meta-analyses have concluded that pathologic fracture is a negative prognostic factor in osteosarcoma. But several confounding variables were not accounted for in the index studies, thereby compromising internal validity. METHODS: A multivariable survival analysis of a retrospective cohort of 131 patients with conventional, high-grade osteosarcoma of the extremity long bones treated with neoadjuvant chemotherapy and surgical resection was performed. RESULTS: There were no significant differences in clinicopathologic variables between the 21 patients who suffered pathologic fracture and the 110 patients who did not in standard bivariable statistical tests. Hazard ratios for decreased overall and disease-free survival of patients with pathologic fracture failed to reach statistical significance in univariable Cox proportional hazard regression. Furthermore, pathologic fracture did not significantly affect patient outcome (hazard ratio for overall survival, 1.15 [95% CI 0.56-2.38], P = 0.71 or disease free survival, 1.01 [95% CI 0.53-1.91], P = 0.98) after controlling for confounding factors not accounted for in prior meta-analyses, such as tumor size, chemotherapy response, and proximal tumor location. CONCLUSIONS: Pathologic fracture is not a significant prognostic factor for extremity osteosarcoma after controlling for other established prognostic factors. Although a useful statistical method, meta-analysis can generate false conclusions if important confounding factors are ignored. Analysis of individual patient data, which would require collaboration among different groups, would circumvent this limitation of meta-analysis. PMID- 26895689 TI - Validated spectrophotometric and chromatographic methods for simultaneous determination of ketorolac tromethamine and phenylephrine hydrochloride. AB - This work describes five simple and reliable spectrophotometric and chromatographic methods for analysis of the binary mixture of ketorolac tromethamine (KTR) and phenylephrine hydrochloride (PHE). Method I is based on the use of conventional Amax and derivative spectrophotometry with the zero crossing technique where KTR was determined using its Amax and (1)D amplitudes at 323 and 341nm respectively, while PHE was determined by measuring the (1)D amplitudes at 248.5nm. Method II involves the application of the ratio spectra derivative spectrophotometry. For KTR, 12MUg/mL PHE was used as a divisor and the (1)DD amplitudes at 265nm were plotted against KTR concentrations; while - by using 4MUg/mL KTR as divisor - the (1)DD amplitudes at 243.5nm were found proportional to PHE concentrations. Method III depends on ratio-difference measurement where the peak to trough amplitudes between 260 and 284nm were measured and correlated to KTR concentration. Similarly, the peak to trough amplitudes between 235 and 260nm in the PHE ratio spectra were recorded. For method IV, the two compounds were separated using Merck HPTLC sheets of silica gel 60 F254 and a mobile phase composed of chloroform/methanol/ammonia (70:30:2, by volume) followed by densitometric measurement of KTR and PHE spots at 320 and 278nm respectively. Method V depends on HPLC-DAD. Effective chromatographic separation was achieved using Zorbax eclipse plus C8 column (4.6*250mm, 5MUm) with a mobile phase consisting of 0.05M o-phosphoric acid and acetonitrile (50:50, by volume) at a flow rate 1mL/min and detection at 313 and 274nm for KTR and PHE respectively. Analytical performance of the developed methods was statistically validated according to the ICH guidelines with respect to linearity, ranges, precision, accuracy, detection and quantification limits. The validated spectrophotometric and chromatographic methods were successfully applied to the simultaneous analysis of KTR and PHE in synthetic mixtures of different proportions and laboratory-made ophthalmic solution. PMID- 26895690 TI - Weight Loss and Variation of Levothyroxine Requirements in Hypothyroid Obese Patients After Bariatric Surgery. AB - BACKGROUND: Obesity and hypothyroidism are both common disorders within the general population. Obese hypothyroid subjects require higher doses of levothyroxine (LT4) compared with normal weight individuals. Previous studies on the effects of bariatric surgery on LT4 dose requirements in hypothyroid subjects have provided conflicting results. The aim of this study was to evaluate the LT4 requirements in a group of obese subjects with acquired hypothyroidism, before and after weight loss achieved by bariatric surgery. METHODS: Ninety-three obese hypothyroid subjects (mean age = 48 +/- 9 years; mean body mass index = 45.9 +/- 5.6 kg/m(2)), were evaluated before and 28 +/- 8 months after bariatric surgery. Changes in the LT4 dose, anthropometric measures, and hormone values were evaluated. In 20 patients, data of body composition, assessed by dual energy X ray absorptiometry, were also analyzed. RESULTS: On average, after weight loss, a significant reduction of the total dose of LT4 was documented (from 130.6 +/- 48.5 to 116.2 +/- 38.6 MUg/day; p < 0.001). The LT4 dose had to be reduced in 47 patients, was unchanged in 34, and had to be increased in 12 patients affected by autoimmune thyroiditis. Reduction of the LT4 dose was proportional to reduction of the lean body mass. CONCLUSIONS: The weight loss achieved with modern surgical bariatric procedures is associated with a reduction of LT4 requirements in most hypothyroid subjects, which appears to be related to a decrease of the lean body mass. Occasionally, a concurrent decline of residual thyroid function, as it occurs in autoimmune thyroiditis, can counteract this phenomenon and eventually produce an increase of LT4 needs. It is believed that during the weight loss phase that follows bariatric surgery, there is no need for preventive adjustments of the LT4 dose, but serum thyroid hormones and thyrotropin should be periodically monitored in order to detect possible variations of LT4 requirements and to allow proper corrections of the therapy. PMID- 26895691 TI - Co-infection assessment in HBV, HCV, and HIV patients in Western Saudi Arabia. AB - To estimate the prevalence of diagnosed and undiagnosed coinfections among HIV, HBV, and HCV infected patients. Retrospective analysis of laboratory records for HIV, HBV, and HCV patients presenting at the HIV outpatient clinic. Serological data including hepatitis B surface antigen (HBsAg), hepatitis B e-antigen (HBeAg), hepatitis B e-antibody (anti-HBe), antibodies to HIV and HCV, anti toxoplasmosis IgG and IgM antibodies, and anti-syphilis antibodies (VDRL) were collected. We obtained data for 628 (218 HCV, 268 HBV, and 142 HIV) patients. Male-to-female ratios were 1:1 for HCV, 3:4 for HBV, and 5:3 for HIV. Age means (SD) were 54.24 (16.40), 44.53 (18.83), and 40.39 (15.92) years for HCV, HBV, and HIV, respectively. In HIV group, the prevalence of HBV and HCV coinfections was 8.5% and 2.8%, respectively. In HBV group, the prevalence of HCV and HIV coinfections was 1.1% and 1.5%, respectively. In HCV group, HIV or HBV coinfections occurred at the same frequency (1.4%). An absence of screening for coinfections was detected in 7.0-48.5% patients as per the group and the infectious agent; which represents an estimated proportion of 20 out of 1,000 patients with an undiagnosed coinfection. Despite a relatively low prevalence of coinfections, a significant proportion of cases remain undiagnosed because of a lack of systematic screening. J. Med. Virol. 88:1545-1551, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26895692 TI - Ganglion cell layer measurements correlate with disease severity in patients with Alzheimer's disease. AB - PURPOSE: To evaluate the thickness of the 10 retinal layers of patients with Alzheimer's disease (AD) using a new segmentation technology of the Spectralis optical coherence tomography (OCT) and to determine whether the thickness of specific layers predicts neurodegeneration or AD severity. METHODS: Patients with AD (n = 150) and age-matched healthy controls (n = 75) were analysed using the segmentation application prototype to automatically segment all retinal layers in a macular scan. Thicknesses of each layer were compared between patients with AD and controls, and between patients with disease durations of less than or at least 3 years. Associations between retinal layer thicknesses, disease duration and AD severity were evaluated. RESULTS: Patients with AD had reduced thickness in the retinal nerve fibre, ganglion cell, inner plexiform and outer nuclear layers (p < 0.05). The inner retinal layers were more affected in patients with long disease duration. Ganglion cell and retinal nerve fibre layer thicknesses were inversely correlated with AD duration and severity. Ganglion cell and inner plexiform layers thicknesses were predictive of axonal damage. CONCLUSIONS: The segmentation application revealed ganglion cell and retinal layer atrophy in patients with AD compared with controls, especially in the inner layers of patients with long disease duration. Ganglion cell layer reduction was associated with increased axonal damage and may predict greater disease severity. PMID- 26895693 TI - Levels of polybrominated diphenyl ethers in house dust in Central Poland. AB - Polybrominated diphenyl ethers (PBDEs) are used as flame retardants in numerous products, from which they are emitted to the environment, including house dust. House dust is a source of human exposure to these compounds by ingestion. The aim of this article was to determine the levels of selected PBDEs in the house dust and indicate their potential sources of origin. PBDE congeners: BDE-47, BDE-99, BDE-153 and BDE-209, were analyzed in 129 samples. The geometric mean levels (and 95% CIs) of the aforementioned congeners amounted to 3.8 (3.1-4.7) ng/g, 4.5 (3.5 5.6) ng/g, 2.2 (2.1-2.4) ng/g and 345 (269-442) ng/g respectively. BDE-209 was the dominant congener in the majority of tested samples. We found a statistically significant correlation between the concentrations of BDE-47 and the computer operating time per day (rs - 0.18) and the living area (rs - 0.20). Statistically significant higher levels of BDE-99 were found in homes where the floor was not replaced during the last 2 years. PMID- 26895694 TI - Passive hip movement measurements related to dynamic motion during gait in hip osteoarthritis. AB - Reduced sagittal plane range of motion (ROM) has been reported in individuals with hip osteoarthritis (OA) both during walking and passive testing. The purpose of this study was to determine if a relationship exists between hip extension ROM recorded during gait and passive hip extension ROM in individuals with moderate and severe hip OA, in comparison to an asymptomatic group. Sagittal plane hip ROM was calculated using skin surface marker trajectories captured during treadmill walking at self-selected speed. Passive hip ROM was measured using standardized position and recording procedures with a goniometer. Sagittal plane extension, flexion, and overall ROM were measured dynamically and passively. A two-way mixed model analysis of variance determined significant differences between groups and between passive and dynamic ROM (alpha = 0.05). Pearson correlations determined relationships between passive and dynamic ROM. Significant group by ROM interactions were found for flexion and extension ROM (p < 0.05). For extension, the severe OA group had less dynamic and passive ROM compared to the other groups and greater passive than dynamic ROM (p < 0.05). For flexion, significant differences in passive ROM existed between all three groups (p < 0.05) whereas no differences were found for dynamic flexion (p < 0.05). Significant correlations between dynamic and passive hip extension were found in the moderate (r = 0.596) and severe OA (r = 0.586) groups, and no correlation was found in the asymptomatic group (r = 0.139). Passive ROM explains variance in dynamic ROM measurements obtained during gait in individuals with moderate and severe hip OA which have implications for the design of treatment strategies targeting walking pathomechanics. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1790-1797, 2016. PMID- 26895695 TI - Sexuality and its object in Freud's 1905 edition of Three Essays on the Theory of Sexuality. AB - Freud's Three Essays on the Theory of Sexuality is one of the grounding texts of 20th century European thinking. In it Freud develops a highly original theory of sexuality for which hysteria (and pathology in general) serves a model to understand human existence. Freud published this text five times during his lifetime. This article wants to reconstruct the first edition with regard to the status and nature of (infantile) sexuality in relation to its object. It investigates how and why this relation changes in the different versions of the text. The reconstruction of the first edition is a crucial, but often forgotten task to understand the genesis of Freudian thinking. PMID- 26895696 TI - The Role of Health Locus of Control in Evaluating Depression and Other Comorbidities in Patients with Chronic Pain Conditions, A Cross-Sectional Study. AB - OBJECTIVE: Chronic pain is significantly influenced by behavioral, cognitive, and emotional factors. Few studies have investigated the health locus of control (HLC)-one's belief regarding where control over one's health lies-as it relates to patients with chronic pain. The purpose of this prospective, cross-sectional study was to examine the relationship between depression and health/pain locus of control (HLC) in adult patients with persistent pain. MATERIAL AND METHODS: A series of questionnaires was administered to chronic pain patients, and these questionnaires were scored and analyzed. Patients were categorized into 3 groups based on health locus of control (internal, chance, powerful-others), which were examined with respect to their depression scores using analysis of variance. RESULTS: A total of 131 patients completed the study: 33% belonged to the internal group, 39% in the chance group, and 28% in the powerful-others group. The 3 groups had depression scores of 40 (SD = 8), 47 (SD = 10), and 42 (SD = 8), respectively. We found significant difference in depressions scores between the chance group and the internal group (P < 0.005) with the chance group having higher depression scores compared to the internal group. CONCLUSIONS: The study shows that patients with an internal locus of control are less depressed compared to patients with fatalistic views on their health/pain in the chance group. The chance dimension of the Multidimensional Health Locus of Control scale was found to be a potential predictor of psychiatric comorbidities such as depression in the chronic pain patient population. PMID- 26895697 TI - Visceral leishmaniasis after orthotopic liver transplantation: a rare cause of infection. AB - Visceral leishmaniasis (VL) was known as an opportunistic infection associated with immunosuppression, particularly related to human immunodeficiency virus infection and rarely to solid organ transplant recipients. We report a case of VL, 6 months after liver transplantation, in a patient who presented with febrile pancytopenia. The diagnosis was made by demonstration of amastigotes in smears from bone marrow. VL is a very rare infection in patients who undergo liver transplantation and, to our knowledge, this is the first case diagnosed in Portugal. PMID- 26895698 TI - Parotidectomy for Parotid Cancer. AB - Parotidectomy for parotid cancer includes management of primary salivary cancer, metastatic cancer to lymph nodes, and direct extension from surrounding structures or cutaneous malignancies. Preoperative evaluation should provide surgeons with enough information to plan a sound operation and adequately counsel patients. Facial nerve sacrifice is sometimes required; but in preoperative functioning nerves, function should be preserved. Although nerve involvement predicts poor outcome, survival of around 50% has been reported for primary parotid malignancy. Metastatic cutaneous squamous cell carcinoma is a high-grade aggressive histology whereby local control for palliation with extended parotidectomy can be achieved; however, overall survival remains poor. PMID- 26895699 TI - [Do proton pump inhibitors increase the risk of myocardial infarction?]. PMID- 26895700 TI - Characteristics of follicular fluid in ovaries with endometriomas. AB - The study of follicular fluid (FF) content nearby endometriomas may assist in elucidating pathophysiology, possible biomarkers related to this disease and the effect of endometriomas on ovarian physiology. As the question "how endometrioma may intrude the physiology of ovarian tissue?" is still open, we aimed to summarize the molecular evidence supporting the idea that endometriomas can negatively influence the content of the surrounding ovarian follicles. An alteration of the iron metabolism and an increased ROS (reactive oxygen species) generation characterize the intrafollicular environment adjacent to endometriomas. Other potentially negative effects include decreased testosterone and anti-Mullerian hormone FF levels although these have been only partially clarified. Alterations in lipid and proteomic patterns have been also observed in FF samples nearby endometriomas. The possibility that endometriomas per se may influence IVF clinical results as a consequence of the detrimental impact on the local intrafollicular environment is also discussed. PMID- 26895703 TI - Small-area spatio-temporal analyses of bladder and kidney cancer risk in Nova Scotia, Canada. AB - BACKGROUND: Bladder and kidney cancers are the ninth and twelfth most common type of cancer worldwide, respectively. Internationally, rates vary ten-fold, with several countries showing rising incidence. This study describes the spatial and spatio-temporal variations in the incidence risk of these diseases for Nova Scotia, a province located in Atlantic Canada, where rates for bladder and kidney cancer exceed those of the national average by about 25% and 35%, respectively. METHODS: Cancer incidence in the 311 Communities of Nova-Scotia was analyzed with a spatial autoregressive model for the case counts of bladder and kidney cancers (3,232 and 2,143 total cases, respectively), accounting for each Community's population and including variables known to influence risk. A spatially continuous analysis, using a geostatistical Local Expectation-Maximization smoothing algorithm, modeled finer-scale spatial variation in risk for south western Nova Scotia (1,810 bladder and 957 kidney cases) and Cape Breton (1,101 bladder, 703 kidney). RESULTS: Evidence of spatial variations in the risk of bladder and kidney cancer was demonstrated using both aggregated Community-level mapping and continuous-grid based localized mapping; and these were generally stable over time. The Community-level analysis suggested that much of this heterogeneity was not accounted for by known explanatory variables. There appears to be a north-east to south-west increasing gradient with a number of south western Communities have risk of bladder or kidney cancer more than 10% above the provincial average. Kidney cancer risk was also elevated in various northeastern communities. Over a 12 year period this exceedance translated in an excess of 200 cases. Patterns of variations in risk obtained from the spatially continuous smoothing analysis generally mirrored those from the Community-level autoregressive model, although these more localized risk estimates resulted in a larger spatial extent for which risk is likely to be elevated. CONCLUSIONS: Modelling the spatio-temporal distribution of disease risk enabled the quantification of risk relative to expected background levels and the identification of high risk areas. It also permitted the determination of the relative stability of the observed patterns over time and in this study, pointed to excess risk potentially driven by exposure to risk factors that act in a sustained manner over time. PMID- 26895702 TI - C-type natriuretic peptide ameliorates pulmonary fibrosis by acting on lung fibroblasts in mice. AB - BACKGROUND: Pulmonary fibrosis has high rates of mortality and morbidity; however, no effective pharmacological therapy has been established. C-type natriuretic peptide (CNP), a member of the natriuretic peptide family, selectively binds to the transmembrane guanylyl cyclase (GC)-B receptor and exerts anti-inflammatory and anti-fibrotic effects in various organs through vascular endothelial cells and fibroblasts that have a cell-surface GC-B receptor. Given the pathophysiological importance of fibroblast activation in pulmonary fibrosis, we hypothesized that the anti-fibrotic and anti-inflammatory effects of exogenous CNP against bleomycin (BLM)-induced pulmonary fibrosis were exerted in part by the effect of CNP on pulmonary fibroblasts. METHODS: C57BL/6 mice were divided into two groups, CNP-treated (2.5 MUg/kg/min) and vehicle, to evaluate BLM-induced (1 mg/kg) pulmonary fibrosis and inflammation. A periostin CNP transgenic mouse model exhibiting CNP overexpression in fibroblasts was generated and examined for the anti-inflammatory and anti-fibrotic effects of CNP via fibroblasts in vivo. Additionally, we assessed CNP attenuation of TGF-beta induced differentiation into myofibroblasts by using immortalized human lung fibroblasts stably expressing GC-B receptors. Furthermore, to investigate whether CNP acts on human lung fibroblasts in a clinical setting, we obtained primary cultured fibroblasts from surgically resected lungs of patients with lung cancer and analyzed levels of GC-B mRNA transcription. RESULTS: CNP reduced mRNA levels of the profibrotic cytokines interleukin (IL)-1beta and IL-6, as well as collagen deposition and the fibrotic area in lungs of mice with bleomycin-induced pulmonary fibrosis. Furthermore, similar CNP effects were observed in transgenic mice exhibiting fibroblast-specific CNP overexpression. In cultured-lung fibroblasts, CNP treatment attenuated TGF-beta-induced phosphorylation of Smad2 and increased mRNA and protein expression of alpha-smooth muscle actin and SM22alpha, indicating that CNP suppresses fibroblast differentiation into myofibroblasts. Furthermore, human lung fibroblasts from patients with or without interstitial lung disease substantially expressed GC-B receptor mRNA. CONCLUSIONS: These data suggest that CNP ameliorates bleomycin-induced pulmonary fibrosis by suppressing TGF-beta signaling and myofibroblastic differentiation in lung fibroblasts. Therefore, we propose consideration of CNP for clinical application to pulmonary fibrosis treatment. PMID- 26895705 TI - Time for the 70 degrees C water precautionary option in the home dilution of powdered infant formula. AB - Powdered infant formulas (PIF) are usually not sterile and may frequently be contaminated by several bacteria strains. Among them, Cronobacter species, previously known as Enterobacter sakazakii, is one of the most harmful, since it might be the causative agent of sepsis and meningitis in newborns and preterm infants during the first weeks of life. The mortality rate of these infections is up to 80 %. Therefore, some precautions are required in the home handling and dilution of PIF. Whereas there is wide consensus about the need that a PIF should be used immediately after being diluted or, if not, stored at < "5 degrees C", still recently the optimal temperature of the water used to dilute PIF is controversial among scientific societies and health agencies. The current knowledge is reviewed in this paper and provides sufficient evidence to cautiously advise the use of hot water at a temperature of "70 degrees C" in the dilution of PIF in order to prevent the Cronobacter sp. contamination and growth. PMID- 26895704 TI - Virus replicon particles expressing porcine reproductive and respiratory syndrome virus proteins elicit immune priming but do not confer protection from viremia in pigs. AB - Porcine reproductive and respiratory syndrome virus (PRRSV) is the causative agent of one of the most devastating and economically significant viral disease of pigs worldwide. The vaccines currently available on the market elicit only limited protection. Recombinant vesicular stomatitis virus (VSV) replicon particles (VRP) have been used successfully to induce protection against influenza A virus (IAV) in chickens and bluetongue virus in sheep. In this study, VSV VRP expressing the PRRSV envelope proteins GP5, M, GP4, GP3, GP2 and the nucleocapsid protein N, individually or in combination, were generated and evaluated as a potential vector vaccine against PRRSV infection. High level expression of the recombinant PRRSV proteins was demonstrated in cell culture. However, none of the PRRSV antigens expressed from VRP, with the exception of the N protein, did induce any detectable antibody response in pigs before challenge infection with PRRSV. After challenge however, the antibody responses against GP5, GP4 and GP3 appeared in average 2 weeks earlier than in pigs vaccinated with the empty control VRP. No reduction of viremia was observed in the vaccinated group compared with the control group. When pigs were co-vaccinated with VRP expressing IAV antigens and VRP expressing PRRSV glycoproteins, only antibody responses to the IAV antigens were detectable. These data show that the VSV replicon vector can induce immune responses to heterologous proteins in pigs, but that the PRRSV envelope proteins expressed from VSV VRP are poorly immunogenic. Nevertheless, they prime the immune system for significantly earlier B-cell responses following PRRSV challenge infection. PMID- 26895706 TI - High-throughput sequencing of cerebrospinal fluid for diagnosis of chronic Propionibacterium acnes meningitis in an allogeneic stem cell transplant recipient. AB - BACKGROUND: A 40-year-old man with chronic myelogenous leukemia presented multiple times over a period of 3 years with episodes of confusion, wide-based gait and falls because of recurrent hydrocephalus despite repeated therapeutic lumbar punctures. These problems occurred in the context of persistent cerebrospinal fluid (CSF) pleocytosis and leptomeningeal enhancement. Extensive diagnostic workups and therapeutic trials had failed to identify a clinically plausible cause or produce any significant improvement in the CSF and neuroimaging abnormalities. METHODS: We used high-throughput metagenomic shotgun sequencing to identify microbes in 2 CSF samples collected from the patient during his illness. These results were compared to sequence data from 1 CSF sample collected during treatment and 5 control CSF samples from other patients. RESULTS: We found sequences representing 53% and 67% of the Propionibacterium acnes genome in 2 CSF samples collected from the patient during his illness. Directed antimicrobial therapy was administered for 6 weeks with resolution of CSF and neuroimaging abnormalities. Sequencing of a sample obtained during treatment demonstrated that the P. acnes levels were decreased to background levels. After insertion of a ventriculo-peritoneal shunt, the patient returned to baseline status. CONCLUSIONS: High-throughput metagenomic shotgun sequencing revealed P. acnes as the cause of chronic meningitis that had eluded conventional attempts at diagnosis. Treatment directed at this organism resulted in cure of the infection and clinical improvement. PMID- 26895707 TI - Exploring occurrence and molecular diversity of betaine lipids across taxonomy of marine microalgae. AB - Betaine lipids (BL) from ten microalgae species of the kingdoms Plantae and Chromista were identified and quantified by HPLC/ESI-TOF-MS. Diacylgyceryl-N trimethylhomoserine (DGTS) was detected in Trebouxiophyceae and Eustigmatophyceae species, whereas Tetraselmis suecica was described as the first green algae containing diacylglyceryl-hydroxymethyl-N,N,N-trimethyl-beta-alanine (DGTA). DGTA molecular species where also characterized in Cryptophyceae species as well as in the Bacillariophyceae diatom Phaeodactylum tricornutum. The Mediophyceae diatom Chaetoceros gracilis had no DGTA, but contained diacylglyceryl carboxyhydroxymethylcholine (DGCC). A principal coordinate (PCO) analysis of microalgae species revealed the existence of three main clusters around each BL type. The first PCO axis (43.9% of total variation) grouped Chlorophyceae, Trebouxiophyceae and Eustigmatophyceae species and positively correlated with DGTS. The second PCO axis (27.8% of total variation) segregated DGTA from DGCC containing species. Cryptophyceae, Bacillariophyceae and Chlorodendrophyceae were the more closely associated species to DGTA. Mediophyceae and Dinophyceae species contained DGCC as the only BL. Molecular diversity varied from the simplest DGCC composition in Gyrodinium dorsum to the highest spectrum of ten different molecular species detected for DGTA (Rhodomonas baltica) and DGCC (C. gracilis). The fatty acid profile of DGTS was very dissimilar to that of the whole lipid cell content. DGTS from Nannochloropsis gaditana was highly unsaturated respecting to total lipids, whereas in Picochlorum atomus DGTS unsaturation was nearly one half to that of total lipids. Dissimilarity between DGTA and total lipid fatty acid profile was minimum among all BL and DGTA fatty acid unsaturation was the maximum observed in the study. New DGCC molecular species enriched in 20:5 were described in Mediophyceae diatoms. Multivariate microalgae ordination using BL as descriptors revealed a higher chemotaxonomic potential than that based on their respective BL fatty acid profile. Nevertheless, taxonomic resolution was improved when fatty acids from the whole cell lipid pool were used. PMID- 26895708 TI - Tremor pattern differentiates drug-induced resting tremor from Parkinson disease. AB - OBJECTIVE: DAT-SPECT, is a well-established procedure for distinguishing drug induced parkinsonism from Parkinson's disease (PD). We investigated the usefulness of blink reflex recovery cycle (BRrc) and of electromyographic parameters of resting tremor for the differentiation of patients with drug induced parkinsonism with resting tremor (rDIP) from those with resting tremor due to PD. METHODS: This was a cross-sectional study. In 16 patients with rDIP and 18 patients with PD we analysed electrophysiological parameters (amplitude, duration, burst and pattern) of resting tremor. BRrc at interstimulus intervals (ISI) of 100, 150, 200, 300, 400, 500 and 750 msec was also analysed in patients with rDIP, patients with PD and healthy controls. All patients and controls underwent DAT-SPECT. RESULTS: Rest tremor amplitude was higher in PD patients than in rDIP patients (p < 0.001), while frequency and burst duration were higher in rDIP than in PD (p < 0.001, p < 0.003, respectively). Resting tremor showed a synchronous pattern in all patients with rDIP, whereas it had an alternating pattern in all PD patients (p < 0.001). DAT-SPECT was normal in rDIP patients while it was markedly abnormal in patients with PD. CONCLUSIONS: In the absence of DAT-SPECT, the pattern of resting tremor can be considered a useful investigation for differentiating rDIP from PD. PMID- 26895709 TI - Autonomous space systems control incorporating automated maneuvers strategies in the presence of parameters uncertainties. AB - The research attempts to deal with the autonomous space systems incorporating new automated maneuvers strategies in the presence of parameters uncertainties. The main subject behind the investigation is to realize the high-resolution small amplitude orbital maneuvers via the first control strategy. And subsequently to realize the large amplitude orbital maneuvers via the second control strategy, as well. There is a trajectory optimization to provide the three-axis referenced commends for the aforementioned overactuated autonomous space system to be able to transfer from the initial orbit to its final ones, in finite burn, as long as the uncertainties of key parameters of the system such as the thrust vector, the center of the gravity, the moments of the inertia and so on are taken into real consideration. The strategies performances are finally considered through a series of experiments and a number of benchmarks to be tangibly verified. PMID- 26895710 TI - Temporal Trends in Hospitalization for Acute Decompensated Heart Failure in the United States, 1998-2011. AB - Estimates of the numbers and rates of acute decompensated heart failure (ADHF) hospitalization are central to understanding health-care utilization and efforts to improve patient care. We comprehensively estimated the frequency, rate, and trends of ADHF hospitalization in the United States. Based on Atherosclerosis Risk in Communities (ARIC) Study surveillance adjudicating 12,450 eligible hospitalizations during 2005-2010, we developed prediction models for ADHF separately for 3 International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 428 discharge diagnosis groups: 428 primary, 428 nonprimary, or 428 absent. We applied the models to data from the National Inpatient Sample (11.5 million hospitalizations of persons aged >=55 years with eligible ICD-9-CM codes), an all-payer, 20% probability sample of US community hospitals. The average estimated number of ADHF hospitalizations per year was 1.76 million (428 primary, 0.80 million; 428 nonprimary, 0.83 million; 428 absent, 0.13 million). During 1998-2004, the rate of ADHF hospitalization increased by 2.0%/year (95% confidence interval (CI): 1.8, 2.5) versus a 1.4%/year (95% CI: 0.8, 2.1) increase in code 428 primary hospitalizations (P < 0.001). In contrast, during 2005-2011, numbers of ADHF hospitalizations were stable (-0.5%/year; 95% CI: -1.4, 0.3), while the numbers of 428-primary hospitalizations decreased by -1.5%/year (95% CI: -2.2, -0.8) (P for contrast = 0.03). In conclusion, the estimated number of hospitalizations with ADHF is approximately 2 times higher than the number of hospitalizations with ICD-9-CM code 428 in the primary position. The trend increased more steeply prior to 2005 and was relatively flat after 2005. PMID- 26895711 TI - Prospective study of proton beam radiation therapy for adjuvant and definitive treatment of thymoma and thymic carcinoma: Early response and toxicity assessment. AB - BACKGROUND AND PURPOSE: Radiation is an important modality in treatment of thymic tumors. However, toxicity may reduce its overall benefit. We hypothesized that double-scattering proton beam therapy (DS-PT) can achieve excellent local control with limited toxicity in patients with thymic malignancies. METHODS AND MATERIALS: Patients with thymoma or thymic carcinoma treated with DS-PT between 2011 and 2015 were prospectively analyzed for toxicity and patterns of failure on an IRB-approved study. RESULTS: Twenty-seven consecutive patients were evaluated. Patients were a median of 56 years and had thymoma (85%). They were treated with definitive (22%), salvage (15%) or adjuvant (63%) DS-PT to a median of 61.2/1.8 Gy [CGE]. No patient experienced grade ?3 toxicity. Acute grade 2 toxicities included dermatitis (37%), fatigue (11%), esophagitis (7%), and pneumonitis (4%). Late grade 2 toxicity was limited to a single patient with chronic dyspnea. At a median follow-up of 2 years, 100% local control was achieved. Three-year regional control, distant control, and overall survival rates were 96% (95% CI 76-99%), 74% (95% CI 41-90%), and 94% (95% CI 63-99%), respectively. CONCLUSIONS: This is the first cohort and prospective series of proton therapy to treat thymic tumors, demonstrating low rates of early toxicity and excellent initial outcomes. PMID- 26895712 TI - Quality of life and functional outcome of male patients with bladder-prostate rhabdomyosarcoma treated with conservative surgery and brachytherapy during childhood. AB - PURPOSE: The aim of this study was to report the long-term results of a conservative local treatment of male patients with bladder-prostate rhabdomyosarcoma (BPRMS) focusing on their outcome and quality of life (QoL). METHODS AND MATERIALS: From 1991 to 2007, 27 male patients were treated by a single team, according to the ongoing European protocols. Surgical procedure was partial cystectomy or partial prostatectomy or both, followed by low-dose-rate interstitial brachytherapy. Three patients died of metastases and two were excluded; 22 patients, who were long-term survivors with their bladder, received a QoL questionnaire derived from the International Workshop on BPRMS. Urodynamic studies were performed when patients had abnormal continence. RESULTS: Median age at surgery was 24 months (14 months-11 years). Median followup after surgery was 10 years (5-21 years); 18 male patients (77%) completed the questionnaire at a median age of 13 years (7-25 years); 13 considered themselves as having a normal QoL, with normal urinary continence (9 of 13) or very rare diurnal dribbling (4 of 13). Four male patients had frequent diurnal dribbling requiring protection for three of them and one was submitted to intermittent catheterism for a postoperative neurogenic bladder. Urodynamic studies were performed in 11 patients with urinary disturbance, often revealing detrusor sphincter dyssynergia. All pubertal patients considered themselves as having normal erections. Three sexually active patients reported having satisfying sex and orgasms. Two patients had normal ejaculations. CONCLUSIONS: The majority of long term male survivors (76%) within this cohort considered themselves as having a normal QoL after the combined conservative local treatment of their BPRMS. PMID- 26895714 TI - Infection risk in elderly people with reduced glycaemic control. PMID- 26895715 TI - Prehospital fast track care for patients with hip fracture: Impact on time to surgery, hospital stay, post-operative complications and mortality a randomised, controlled trial. AB - INTRODUCTION: Ambulance organisations in Sweden have introduced prehospital fast track care (PFTC) for patients with suspected hip fracture. This means that the ambulance nurse starts the pre-operative procedure otherwise implemented at the accident & emergency ward (A&E) and transports the patient directly to the radiology department instead of A&E. If the diagnosis is confirmed, the patient is transported directly to the orthopaedic ward. No previous randomised, controlled studies have analysed PFTC to describe its possible advantages. The aim of this study is to examine whether PFTC has any impact on outcomes such as time to surgery, length of stay, post-operative complications and mortality. METHODS: The design of this study is a prehospital randomised, controlled study, powered to include 400 patients. The patients were randomised into PFTC or the traditional care pathway (A&E group). RESULTS: Time from arrival to start for X ray was faster for PFTC (mean, 28 vs. 145 min; p<0.001), but the groups did not differ with regard to time from start of X-ray to start of surgery (mean 18.40 h in both groups). No significant differences between the groups were observed with regard to: time from arrival to start of surgery (p=0.07); proportion operated within 24h (79% PFTC, 75% A&E; p=0.34); length of stay (p=0.34); post-operative complications (p=0.75); and 4 month mortality (18% PFTC, 15% A&E p=0.58). CONCLUSION: PFTC improved time to X-ray and admission to a ward, as expected, but did not significantly affect time to start of surgery, length of stay, post operative complications or mortality. These outcomes were probably affected by other factors at the hospital. Patients with either possible life-threatening conditions or life-threatening conditions prehospital were excluded. PMID- 26895716 TI - Ribophorin II is involved in the tissue factor expression mediated by phosphatidylserine-dependent antiprothrombin antibody on monocytes. AB - OBJECTIVE: Phosphatidylserine-dependent, also called aPS-PT, recognizes the phosphatidylserine-prothrombin complex, which is associated with APS. We have previously reported that aPS-PT induces tissue factor (TF) expression on monocytes through the p38 mitogen-activated protein kinase pathway. However, the cell surface interaction between prothrombin and aPS-PT, which is involved in the activation of cell-signalling pathways, has remained unknown. The objective of this study was to identify membrane proteins involved in the binding of prothrombin and aPS-PT to monocyte surfaces as well as the induction of TF expression. METHODS: RAW264.7 cells with FLAG-tagged prothrombin were incubated and separated using affinity chromatography with anti-FLAG antibody-conjugated Sepharose beads. Immunopurified proteins were then analysed by an online nano liquid chromatography-tandem mass spectrometry. The binding between prothrombin and the identified protein, ribophorin II (RPN2), was analysed by ELISA and surface plasmon resonance. To elucidate the role of RPN2 in TF expression, the TF mRNA level in RAW264.7 cells treated with RPN2 small interfering RNA was determined by quantitative real-time PCR (qPCR). RESULTS: RPN2 was identified as a candidate molecule involved in the binding of prothrombin to the cell surface. The binding between prothrombin and RPN2 was confirmed by ELISA and surface plasmon resonance. RAW264.7 cells treated with RPN2 small interfering RNA showed significant reduction of the TF expression mediated by prothrombin and a mouse monoclonal aPS-PT. CONCLUSION: We identified that RPN2 is one of the prothrombin binding proteins on monocyte surfaces, suggesting that RPN2 is involved in the pathophysiology of thrombosis in patients with APS. PMID- 26895717 TI - Groups call for "dangerous" trial of doctors' working hours to stop. PMID- 26895713 TI - Experimental evolution in biofilm populations. AB - Biofilms are a major form of microbial life in which cells form dense surface associated communities that can persist for many generations. The long-life of biofilm communities means that they can be strongly shaped by evolutionary processes. Here, we review the experimental study of evolution in biofilm communities. We first provide an overview of the different experimental models used to study biofilm evolution and their associated advantages and disadvantages. We then illustrate the vast amount of diversification observed during biofilm evolution, and we discuss (i) potential ecological and evolutionary processes behind the observed diversification, (ii) recent insights into the genetics of adaptive diversification, (iii) the striking degree of parallelism between evolution experiments and real-life biofilms and (iv) potential consequences of diversification. In the second part, we discuss the insights provided by evolution experiments in how biofilm growth and structure can promote cooperative phenotypes. Overall, our analysis points to an important role of biofilm diversification and cooperation in bacterial survival and productivity. Deeper understanding of both processes is of key importance to design improved antimicrobial strategies and diagnostic techniques. PMID- 26895718 TI - Aging and multiple sclerosis. AB - The life expectancy and average age of persons with multiple sclerosis (MS) have increased significantly during the last two decades. The introduction of disease modifying therapies and a better delineation and understanding of the superimposed comorbidities often diagnosed in MS patients are probably the most important factors accountable for the increase in aging MS population worldwide. Healthcare teams must therefore address the problems arising due to advancing age superimposed on this chronic neurologic disease. In this review, we focus on the physiology of aging, its effects on MS disease course, and the pathological and immunological changes associated with aging and disease progression. Additionally, we discuss the common comorbidities that occur in aging persons with MS that may arise either as a result of the aging process or from relentless chronic MS disease progression as well as the challenges on differentiating the two processes for a more appropriate therapeutic approach. PMID- 26895719 TI - Development of oil-spill sorbent from straw biomass waste: Experiments and modeling studies. AB - The recovery of oil spilled on land or water has become an important issue due to environmental regulations. Canadian biomasses as fibrous materials are naturally renewable and have the potential to absorb oil-spills at different ranges. In this work, four Canadian biomasses were examined in order to evaluate their oil affinities and study parameters that could affect oil affinity when used as sorbent, such as average particle size, surface coating and reusability. Moreover, one oil sorption model was adopted and coupled with another developed model to approximate and verify the experimental findings of the oil sorbent biomasses. At an average particle size of 150-1000 MUm, results showed that barley straw biomass had the highest absorbency value at 6.07 g/g, while flax straw had the lowest value at 3.69 g/g. Wheat and oat straws had oil absorbency values of 5.49 and 5.00 g/g, respectively. An average particle size of 425-600 MUm indicated better absorbency values for oat and wheat straws. Furthermore, the thermal stability study revealed major weight recovery for two flame retardant coatings at hemicellulose and lignocellulose degradation temperature ranges. It was also found that oat straw biomass could be regenerated and used for many sorption/desorption cycles, as the reusability experiment showed only a 18.45% reduction in the oil absorbency value after six consecutive cycles. The developed penetration absorbency (PA) model showed oat straw adsorbed oil at the inter particle level; and, the results of the sorption capacity model coupled with the PA model excellently predicted the oil sorption of raw and coated oat straws. PMID- 26895720 TI - Derivation of risk indices and analysis of variablility for the management of incidents involving the transport of nuclear materials in the Northern Seas. AB - The transport of nuclear or radioactive materials and the presence of nuclear powered vessels pose risks to the Northern Seas in terms of potential impacts to man and environment as well socio-economic impacts. Management of incidents involving actual or potential releases to the marine environment are potentially difficult due to the complexity of the environment into which the release may occur and difficulties in quantifying risk to both man and environment. In order to address this, a state of the art oceanographic model was used to characterize the underlying variability for a specific radionuclide release scenario. The resultant probabilistic data were used as inputs to transfer and dose models providing an indication of potential impacts for man and environment This characterization was then employed to facilitate a rapid means of quantifying risk to man and the environment that included and addressed this variability. The radionuclide specific risk indices derived can be applied by simply multiplying the reported values by the magnitude of the source term and thereafter summing over all radionuclides to provide an indication of total risk. PMID- 26895721 TI - A dynamic simulation/optimization model for scheduling restoration of degraded military training lands. AB - Intensive use of military vehicles on Department of Defense training installations causes deterioration in ground surface quality. Degraded lands restrict the scheduled training activities and jeopardize personnel and equipment safety. We present a simulation-optimization approach and develop a discrete dynamic optimization model to determine an optimum land restoration for a given training schedule and availability of financial resources to minimize the adverse effects of training on military lands. The model considers weather forecasts, scheduled maneuver exercises, and unique qualities and importance of the maneuver areas. An application of this approach to Fort Riley, Kansas, shows that: i) starting with natural conditions, the total amount of training damages would increase almost linearly and exceed a quarter of the training area and 228 gullies would be formed (mostly in the intensive training areas) if no restoration is carried out over 10 years; ii) assuming an initial state that resembles the present conditions, sustaining the landscape requires an annual restoration budget of $957 thousand; iii) targeting a uniform distribution of maneuver damages would increase the total damages and adversely affect the overall landscape quality, therefore a selective restoration strategy may be preferred; and iv) a proactive restoration strategy would be optimal where land degradations are repaired before they turn into more severe damages that are more expensive to repair and may pose a higher training risk. The last finding can be used as a rule-of-thumb for land restoration efforts in other installations with similar characteristics. PMID- 26895722 TI - Recovery of valuable materials from spent NIMH batteries using spouted bed elutriation. AB - In recent years, a great increase in the generation of spent batteries occurred. Then, efficient recycling ways and correct disposal of hazardous wastes are necessary. An alternative to recover the valuable materials from spent NiMH batteries is the spouted bed elutriation. The aim of this study was to apply the mechanical processing (grinding and sieving) followed by spouted bed elutriation to separate the valuable materials present in spent NiMH batteries. The results of the manual characterization showed that about 62 wt.% of the batteries are composed by positive and negative electrodes. After the mechanical separation processes (grinding, sieving and spouted bed elutriation), three different fractions were obtained: 24.21 wt.% of metals, 28.20 wt.% of polymers and 42.00 wt.% of powder (the positive and negative electrodes). It was demonstrated that the different materials present in the spent NiMH batteries can be efficiently separated using a simple and inexpensive mechanical processing. PMID- 26895723 TI - Effectiveness of a Web-Based Simulation in Improving Nurses' Workplace Practice With Deteriorating Ward Patients: A Pre- and Postintervention Study. AB - BACKGROUND: Nurses play an important role in detecting patients with clinical deterioration. However, the problem of nurses failing to trigger deteriorating ward patients still persists despite the implementation of a patient safety initiative, the Rapid Response System. A Web-based simulation was developed to enhance nurses' role in recognizing and responding to deteriorating patients. While studies have evaluated the effectiveness of the Web-based simulation on nurses' clinical performance in a simulated environment, no study has examined its impact on nurses' actual practice in the clinical setting. OBJECTIVE: The objective of this study was to evaluate the impact of Web-based simulation on nurses' recognition of and response to deteriorating patients in clinical settings. The outcomes were measured across all levels of Kirkpatrick's 4-level evaluation model with clinical outcome on triggering rates of deteriorating patients as the primary outcome measure. METHODS: A before-and-after study was conducted on two general wards at an acute care tertiary hospital over a 14-month period. All nurses from the two study wards who undertook the Web-based simulation as part of their continuing nursing education were invited to complete questionnaires at various time points to measure their motivational reaction, knowledge, and perceived transfer of learning. Clinical records on cases triggered by ward nurses from the two study wards were evaluated for frequency and types of triggers over a period of 6 months pre- and 6 months postintervention. RESULTS: The number of deteriorating patients triggered by ward nurses in a medical general ward increased significantly (P<.001) from pre- (84/937, 8.96%) to postintervention (91/624, 14.58%). The nurses reported positively on the transfer of learning (mean 3.89, SD 0.49) from the Web-based simulation to clinical practice. A significant increase (P<.001) on knowledge posttest score from pretest score was also reported. The nurses also perceived positively their motivation (mean 3.78, SD 0.56) to engage in the Web-based simulation. CONCLUSIONS: This study provides evidence on the effectiveness of Web based simulation in improving nursing practice when recognizing and responding to deteriorating patients. This educational tool could be implemented by nurse educators worldwide to address the educational needs of a large group of hospital nurses responsible for patients in clinical deterioration. PMID- 26895724 TI - Evidence based policy making in the European Union: the role of the scientific community. AB - In the times when the acquis of the European Union (EU) has developed so far as to reach a high level of technical complexity, in particular in certain policy fields such as environmental legislation, it is important to look at what kind of information and data policy decisions are based on. This position paper looks at the extent to which evidence-based decision-making process is being considered in the EU institutions when it comes to adopting legislation in the field of environment at the EU level. The paper calls for closer collaboration between scientists and decision-makers in view of ensuring that correct data is understood and taken into consideration when drafting, amending, negotiating and adopting new legal texts at all levels of the EU decision-making process. It concludes that better awareness of the need for such collaboration among the decision-makers as well as the scientific community would benefit the process and quality of the final outcomes (legislation). PMID- 26895725 TI - Selected Fe and Mn (nano)oxides as perspective amendments for the stabilization of As in contaminated soils. AB - An amorphous Mn oxide (AMO), nanomaghemite, and nanomagnetite were used as potential amendments reducing the mobility of As in three contrasting contaminated soils differing in origin of As contamination. Adsorption experiments and XPS analyses combined with incubation batch experiments and pH static leaching tests were used. The AMO showed excellent adsorption capacity for As(V) reaching a maximum of 1.79 mmol g(-1) at pH 7 and 8. Interestingly, the adsorption capacity in this case decreases with decreasing pH, probably as a result of AMO dissolution at lower pH values. Chemical sorption of As(V) onto AMO was further confirmed with XPS. Both Fe nano-oxides proved the highest adsorption capacity at pH 4 reaching 11 mg g(-1) of adsorbed As(V). The AMO was also the most efficient amendment for decreasing As concentrations in soil solutions during 8 weeks of incubation. Additionally, pH-static leaching tests were performed at pH 4, 5, 6, 7, and natural pH (not adjusted) and AMO again proved the highest ability to decrease As content in leachate. On the other hand, strong dissolution of this amendment at lower pH values (especially pH 4) was observed. For that reason, AMO appears as a promising stabilizing agent for As, especially in neutral, alkaline, or slightly acidic soils, where As(V) species are expected to be more mobile. PMID- 26895726 TI - Developmental toxicity of PFOS and PFOA in great cormorant (Phalacrocorax carbo sinensis), herring gull (Larus argentatus) and chicken (Gallus gallus domesticus). AB - Perfluoroalkyl acids (PFAAs) are found globally in environmental samples and have been studied in various species. In this study, we compare the sensitivity of three avian species to the toxic effects of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA). Eggs of great cormorant (Phalacrocorax carbo sinensis), herring gull (Larus argentatus) and the domestic White Leghorn chicken (Gallus gallus domesticus) were exposed in ovo by injection into the air sac. Effects on embryo survival were observed following exposure to PFOS and PFOA in chicken and herring gull. Chicken was found to be the most sensitive species with 50 % reduced embryo survival at 8.5 MUg/g egg for PFOS and 2.5 MUg/g egg for PFOA. Cormorant was shown to be the least sensitive species. The difference in sensitivity between chicken and herring gull was a factor of 2.7 for PFOS and 3.5 for PFOA. Between chicken and great cormorant, the sensitivity difference was 2.6 for PFOS and 8.2 for PFOA. Effects on embryo survival were seen at egg injection doses of PFOS close to levels found in environmental samples from wild birds, indicating that PFOS could be having effects in highly exposed populations of birds. This study also shows that there are differences in species sensitivity to PFOS and PFOA that should be taken into consideration in avian wildlife risk assessment. PMID- 26895727 TI - Idiopathic Hypersomnia and Hypersomnolence Disorder: A Systematic Review of the Literature. AB - BACKGROUND: Hypersomnia is a common complaint in medical offices. Often patients are given psychiatric diagnoses, but a primary sleep disorder may be present. The new diagnosis of "hypersomnolence disorder" (HD) in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition is a primary sleep disorder most similar to the diagnosis "idiopathic hypersomnia" (IH) in sleep literature and can be missed in psychiatric settings. METHODS: A systematic review of the computerized databases PubMed, EMBASE, Web of Science, and Psychinfo using the search criteria "idiopathic AND (hypersomnolence OR hypersomnia)," as well as "hypersomnolence disorder was conducted." Articles were included if they were in English and included information regarding the epidemiology, diagnosis, pathophysiology, or treatment of IH or HD. Where relevant, weighted means and 95% CI were calculated based on the number of subjects in each study. RESULTS: A total of 143 articles discussed IH, whereas no articles were found regarding HD. Most articles were review articles, prospective studies, or studies of pathophysiology. IH is found in approximately 0.02%-0.010% of the general population, has a mean age of onset of 21.8 years, and is associated with several somatic symptoms. Alterations in histaminergic or dopaminergic signaling may be involved in IH. Treatment with modafinil or other stimulants appears moderately effective. IH can be differentiated from psychiatric hypersomnolence by formal polysomnography. CONCLUSIONS: IH and HD are relatively uncommon disorders and little is known about them. However, they are distinct from psychiatric disorders and respond well to treatment once properly identified. PMID- 26895729 TI - GERD: An Alternative Perspective. AB - BACKGROUND: Gastroesophageal reflux disease (GERD) is a prevalent disease caused by multiple facets of factors. Current Western Medicine treatment of GERD focuses mainly on symptom alleviation. Although proton-pump inhibitors are known to alleviate symptoms in most patients, a significant portion of patients continue to present GERD. OBJECTIVE: Given multiple factors, including the involvement of psychosocial influences, that contribute to the pathogenesis of GERD, we sought to look beyond the current available treatments for a multitargeting therapy to combat this disease. Traditional Chinese Medicine, with a history of more than 2000 years, is known for its holistic approach in the treatment of human body. METHODS: In this article, we aim to review the ancient Traditional Chinese Medicine literature and current Traditional Chinese Medicine studies related to GERD, thereby presenting the understanding of GERD from a TCM perspective. PMID- 26895728 TI - Toronto Bariatric Interprofessional Psychosocial Assessment Suitability Scale: Evaluating A New Clinical Assessment Tool for Bariatric Surgery Candidates. AB - BACKGROUND: Patients who are referred for possible bariatric surgery (BS) intervention undergo a series of assessments conducted by an interdisciplinary health care team to determine suitability for surgery. Herein, we report the initial validation and reliability studies of the Bariatric Interprofessional Psychosocial Assessment Suitability Scale (BIPASS) and its relationship to interdisciplinary psychosocial assessment practices for BS. METHODS: This study was conducted at the Toronto Western Hospital, a Level 1A BS center of excellence accredited by the American College of Surgeons. Phase I: a total of 4 blinded raters applied the BIPASS to 31 randomly selected BS cases referred to our program to establish interrater reliability. Phase II: in all, 3 raters with clinical experience in bariatric psychosocial care applied the BIPASS to 54 randomly selected BS cases. RESULTS: In total, 46 of 54 (85.1%) patients were women. The median age of all patient cases was 49 years (range: 21-74). Raters' BIPASS scores ranged from 4-52 (median = 19.24, standard deviation =10.38). BIPASS scores were highly predictive of the BS psychosocial outcome (area under curve = 0.915; 95% CI: 0.844-0.985; p < 0.001). A BIPASS score of >=16 was chosen as the cutoff score for further clinical assessment before proceeding with surgical evaluation based on a receiver operating characteristic curve analysis (sensitivity = 0.839; specificity = 0.783). The instrument has very good interrater reliability (Pearson correlation coefficient = 0.847) even among novice raters. CONCLUSION: The findings show that the BIPASS is a comprehensive screening tool in the psychosocial assessment of BS candidates, which standardizes the evaluation process and systematically identify at-risk patients for negative outcomes after BS. PMID- 26895730 TI - Investigation of receptor binding and functional characteristics of hemopressin(1 7). AB - The orally active, alpha-hemoglobin derived hemopressin (PVNFKFLSH, Hp(1-9)) and its truncated (PVNFKFL, Hp(1-7) and PVNFKF, Hp(1-6)) and extended ((R)VDPVNFKFLSH, VD-Hp(1-9) and RVD-Hp(1-9)) derivatives have been postulated to be the endogenous peptide ligands of the cannabinoid receptor type 1 (CB1). In an attempt to create a versatile peptidic research tool for the direct study of the CB1 receptor-peptide ligand interactions, Hp(1-7) was radiolabeled and in vitro characterized in rat and CB1 knockout mouse brain membrane homogenates. In saturation and competition radioligand binding studies, [(3)H]Hp(1-7) labeled membrane receptors with high densities and displayed specific binding to a receptor protein, but seemingly not to the cannabinoid type 1, in comparison the results with the prototypic JWH-018, AM251, rimonabant, Hp(1-9) and RVD-Hp(1-9) (pepcan 12) ligands in both rat brain and CB1 knockout mouse brain homogenates. Furthermore, functional [(35)S]GTP gammaS binding studies revealed that Hp(1-7) and Hp(1-9) only weakly activated G-proteins in both brain membrane homogenates. Based on our findings and the latest literature data, we assume that the Hp(1-7) peptide fragment may be an allosteric ligand or indirect regulator of the endocannabinoid system rather than an endogenous ligand of the CB1 receptor. PMID- 26895731 TI - Streptophyte Terrestrialization in Light of Plastid Evolution. AB - Key steps in evolution are often singularities. The emergence of land plants is one such case and it is not immediately apparent why. A recent analysis found that the zygnematophycean algae represent the closest relative to embryophytes. Intriguingly, many exaptations thought essential to conquer land are common among various streptophytes, but zygnematophycean algae share with land plants the transfer of a few plastid genes to the nucleus. Considering the contribution of the chloroplast to terrestrialization highlights potentially novel exaptations that currently remain unexplored. We discuss how the streptophyte chloroplast evolved into what we refer to as the embryoplast, and argue this was as important for terrestrialization by freshwater algae as the host cell-associated exaptations that are usually focused upon. PMID- 26895732 TI - Force-Driven Polymerization and Turgor-Induced Wall Expansion. AB - While many molecular players involved in growth control have been identified in the past decades, it is often unknown how they mechanistically act to induce specific shape changes during development. Plant morphogenesis results from the turgor-induced yielding of the extracellular and load-bearing cell wall. Its mechanochemical equilibrium appears as a fundamental link between molecular growth regulation and the effective shape evolution of the tissue. We focus here on force-driven polymerization of the cell wall as a central process in growth control. We propose that mechanical forces facilitate the insertion of wall components, in particular pectins, a process that can be modulated through genetic regulation. We formalize this idea in a mathematical model, which we subsequently test with published experimental results. PMID- 26895734 TI - Editorial. PMID- 26895733 TI - A good preoperative response to transcutaneous electrical nerve stimulation predicts a better therapeutic effect of implanted occipital nerve stimulation in pharmacologically intractable headaches. AB - Occipital nerve stimulation (ONS) is a surgical approach to treat patients with medically intractable chronic headache disorders. However, no preoperative test has been yet validated to allow candidates to be selected for implantation. In this study, the analgesic efficacy of transcutaneous electrical nerve stimulation (TENS) was tested for 1 to 3 months in 41 patients with pharmacologically intractable headache disorders of various origins, using a new technique of electrode placement over the occipital nerve. ONS electrodes were subsequently implanted in 33 patients (occipital neuralgia [n=15], cervicogenic headache [n=7], cluster headache [n=6], chronic migraine [n=5]) who had responded at least moderately to TENS. Assessment was performed up to five years after implantation (three years on average), based on the mean and maximum daily pain intensity scored on a 0-10 visual analogue scale and the number of headache days per month. Both TENS and chronic ONS therapy were found to be efficacious (57-76% improvement compared to baseline on the various clinical variables). The efficacy of ONS was better in cases of good or very good preoperative response to TENS than in cases of moderate response to TENS. Implanted ONS may be a valuable therapeutic option in the long term for patients with pharmacologically intractable chronic headache. Although we cannot conclude in patients with poor or no response to TENS, a good or very good response to TENS can support the indication of ONS therapy. This preoperative test could particularly be useful in patients with chronic migraine, in whom it may be difficult to indicate an invasive technique of cranial neurostimulation. PMID- 26895735 TI - Adjuvant Therapy in Pancreas Cancer: Does It Influence Patterns of Recurrence? AB - BACKGROUND: Level 1 data demonstrate that adjuvant chemotherapy (ACT) improves survival after surgical resection of pancreatic ductal adenocarcinoma (PDAC), (adjuvant gemcitabine, CONKO-001 study; adjuvant 5-FU, ESPAC3 study). The role of adjuvant chemoradiation therapy (ACRT) remains controversial. What is less clear is whether adjuvant therapy influences patterns of recurrence. The purpose of this study was to perform the first multicenter study analyzing patterns of recurrence after adjuvant therapy for PDAC. STUDY DESIGN: Patients undergoing resection for PDAC from 8 medical centers over a 10-year period were analyzed. Demographics, tumor characteristics, operative treatment, type of adjuvant therapy, recurrence pattern, and survival were reviewed. Using Cox-proportional hazards multivariate (MV) regression, the impact of ACT and ACRT on overall survival (OS), local recurrence (LR), and distant recurrence (DR) was investigated. RESULTS: There were 1,130 patients who were divided into those having surgery alone (n = 392), ACT (n = 291), or ACRT (n = 447). Median follow up was 18 months. Compared with patients undergoing surgery alone, ACT, but not ACRT, demonstrated a significant OS advantage on MV analysis. Patients receiving ACT had significantly fewer recurrences (LR and DR); those receiving ACRT had significantly less LR but not DR. On subset MV analysis, ACT and ACRT resulted in less LR in patients with lymph node (LN) positive and margin negative disease. No improvements in LR, DR, or OS were seen in margin positive patients with either ACT or ACRT. CONCLUSIONS: This is the first analysis demonstrating differences in recurrence patterns in PDAC patients based on type of adjuvant therapy. Adjuvant chemotherapy provided an OS advantage likely related to its effect on reducing both LR and DR. Adjuvant chemoradiation therapy appears to decrease LR, but not DR, and therefore has less impact on OS. Future investigations and treatment protocols should consider additional ACT rather than ACRT in the treatment of PDAC. PMID- 26895737 TI - Hepatitis C virus infection induces elevation of CXCL10 in human brain microvascular endothelial cells. AB - Hepatitis C virus (HCV) primarily infects liver tissues, while pathogenesis of extrahepatic tissues has been reported. About 50% of patients with HCV infection suffer from neurological disease. The underlying molecular mechanisms remain unclear. In the present study, we aimed to investigate the induction of CXC chemokine ligand 10 (CXCL10) in human brain microvascular endothelial cells (HBMECs) by HCV infection. CXCL10 and its receptor CXCR3 were constitutively expressed in HBMECs. HCV infection induced CXCL10 elevation in HBMECs. The elevation of CXCL10 in HBMECs was eliminated when HCV infection was blocked by neutralizing antibodies. NF-kappaB is a positive regulator for CXCL10 transcription. HCV infection led to an increased phosphorylation of NF-kappaB (ser536) in HBMECs, and CXCL10 induced by HCV was slightly decreased when an inhibitor of NF-kappaB was added. IL1 beta and IFN gama were also upregulated in HCV infected HBMECs, and could be depressed by inhibitor of NF-kappaB. Thus, HCV infection leads to upregulated expression of CXCL10 in HBMECs, which is probably via the phosphorylation of NF-kappaB. The findings of this study provide potential mechanisms and novel targets for HCV induced neuroinflammation. J. Med. Virol. 88:1596-1603, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26895738 TI - Influence of Sae-regulated and Agr-regulated factors on the escape of Staphylococcus aureus from human macrophages. AB - Although Staphylococcus aureus is not a classical intracellular pathogen, it can survive within phagocytes and many other cell types. However, the pathogen is also able to escape from cells by mechanisms that are only partially understood. We analysed a series of isogenic S. aureus mutants of the USA300 derivative JE2 for their capacity to destroy human macrophages from within. Intracellular S. aureus JE2 caused severe cell damage in human macrophages and could efficiently escape from within the cells. To obtain this full escape phenotype including an intermittent residency in the cytoplasm, the combined action of the regulatory systems Sae and Agr is required. Mutants in Sae or mutants deficient in the Sae target genes lukAB and pvl remained in high numbers within the macrophages causing reduced cell damage. Mutants in the regulatory system Agr or in the Agr target gene psmalpha were largely similar to wild-type bacteria concerning cell damage and escape efficiency. However, these strains were rarely detectable in the cytoplasm, emphasizing the role of phenol-soluble modulins (PSMs) for phagosomal escape. Thus, Sae-regulated toxins largely determine damage and escape from within macrophages, whereas PSMs are mainly responsible for the escape from the phagosome into the cytoplasm. Damage of macrophages induced by intracellular bacteria was linked neither to activation of apoptosis-related caspase 3, 7 or 8 nor to NLRP3-dependent inflammasome activation. PMID- 26895736 TI - The Locus Coeruleus: Essential for Maintaining Cognitive Function and the Aging Brain. AB - Research on cognitive aging has focused on how decline in various cortical and hippocampal regions influence cognition. However, brainstem regions play essential modulatory roles, and new evidence suggests that, among these, the integrity of the locus coeruleus (LC)-norepinephrine (NE) system plays a key role in determining late-life cognitive abilities. The LC is especially vulnerable to toxins and infection and is often the first place Alzheimer's-related pathology appears, with most people showing at least some tau pathology by their mid-20s. On the other hand, NE released from the LC during arousing, mentally challenging, or novel situations helps to protect neurons from damage, which may help to explain how education and engaging careers prevent cognitive decline in later years. PMID- 26895740 TI - Contraception usage and timing of pregnancy among pregnant teenagers in Cape Town, South Africa. AB - OBJECTIVE: To evaluate knowledge and use of contraception among pregnant teenagers in the Cape Town metropolitan area. METHODS: A cross-sectional study enrolled women aged 16 to 19 years who were pregnant and attending prenatal clinics, and prenatal and labor wards at regional hospitals and midwife-run obstetric clinics in the Cape Town area between March 1, 2011 and September 30, 2011. Data were collected using an administered questionnaire. RESULTS: The study enrolled 314 participants. Of the participants, 240 (76.4%) felt their pregnancies had occurred at the "wrong time" but only 38 (12.1%) were using contraception at the time of conception. The form of contraception that participants most commonly had knowledge of was injectable hormonal contraception (274 [87.3%]). Contraception use was low, with 126 (40.1%) participants having never used contraception. The forms of contraception used most commonly were the male condom (106 [33.8%]) and injectable contraception (98 [31.2%]). The majority of participants found it easy to get contraception (192 [61.1%]) and felt that information regarding contraception was readily available (233 [74.2%]). CONCLUSION: Contraception use is suboptimal but this may not simply be a reflection of ineffective family-planning services. Further research is needed to fully explain the lack of contraceptive use in this population. PMID- 26895739 TI - Substrain-specific differences in bone parameters, alpha-2-macroglobulin circulating levels, and osteonecrosis incidence in a rat model. AB - Osteonecrosis of the femoral head (ONFH) is a potentially devastating complication that occurs in up to 40% of young adults receiving chronic glucocorticoid (GC) therapy. Through a validated GC therapy rat model, we have previously shown that Wistar Kyoto (WK) rats exhibit a genetic susceptibility to GC-induced ONFH compared to Sasco Fischer (F344) rats. We have undertaken this study in order to investigate differences between these two strains for their bone parameters, alpha-2-macroglobulin (A2M) circulating levels and incidence of GC-induced osteonecrosis of the femoral head. WK and F344 rats were treated either with 1.5 mg/kg/day of prednisone or placebo for 6 months. Blood was taken every month. The femoral heads were harvested for histological examination to detect ONFH and analyzed with micro-computed tomography. After 3 months of GC therapy, plasma A2M was elevated in treated rats only. GC-treated WK rats exhibited histological evidence of early ONFH through higher rates of cellular apoptosis and empty osteocyte lacunae in the subchondral bone compared to placebos and to F344 rats. Furthermore, micro-CT analysis exhibited femoral head collapse only in GC-treated WK rats. Interestingly, GC-treated F344 rats exhibited significant micro-CT changes, but such changes were less concentrated in the articular region and were accompanied histologically with increased marrow fat. These uCT and histological findings suggest that elevated A2M serum level is not predictive and suitable as an indicative biomarker for early GC-induced ONFH in rodents. Elevated A2M levels observed during GC treatment suggests that it plays role in the host reparative response to GC-associated effects. (c) 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1183-1194, 2017. PMID- 26895741 TI - Passenger thermal comfort and behavior: a field investigation in commercial aircraft cabins. AB - Passengers' behavioral adjustments warrant greater attention in thermal comfort research in aircraft cabins. Thus, a field investigation on 10 commercial aircrafts was conducted. Environment measurements were made and a questionnaire survey was performed. In the questionnaire, passengers were asked to evaluate their thermal comfort and record their adjustments regarding the usage of blankets and ventilation nozzles. The results indicate that behavioral adjustments in the cabin and the use of blankets or nozzle adjustments were employed by 2/3 of the passengers. However, the thermal comfort evaluations by these passengers were not as good as the evaluations by passengers who did not perform any adjustments. Possible causes such as differences in metabolic rate, clothing insulation and radiation asymmetry are discussed. The individual difference seems to be the most probable contributor, suggesting possibly that passengers who made adjustments had a narrower acceptance threshold or a higher expectancy regarding the cabin environment. Local thermal comfort was closely related to the adjustments and significantly influenced overall thermal comfort. Frequent flying was associated with lower ratings for the cabin environment. PMID- 26895743 TI - Effects of Flexibility in Coping with Menstrual Pain on Depressive Symptoms. AB - Coping flexibility refers to the ability to discontinue an ineffective coping strategy and replace it with a more effective alternative. The coping flexibility hypothesis (CFH) predicts that more flexible coping will produce more adaptive outcomes. This study tested CFH validity among young Japanese women with menstrual pain. A total of 186 college students, who reported menstrual pain as being the most frequent pain they suffered over the past year, completed questionnaires related to coping flexibility and strategies for dealing with menstrual pain. Additionally, they reported on later depressive symptoms experienced during menstruation. A hierarchical multiple regression analysis showed that menstrual pain coping flexibility was significantly associated with reduced depressive symptoms during menstruation, even after controlling for the effects of menstrual pain intensity and coping strategies. Thus, the CFH was supported by the data obtained from menstrual pain sufferers in college. PMID- 26895742 TI - Under-5-Years Child Mortality Due to Congenital Anomalies: A Retrospective Study in Urban and Rural China in 1996-2013. AB - INTRODUCTION: Congenital anomalies (CAs) contribute significantly to under-5 years child mortality (U5M) throughout the world. This study analyzed trends in the CA-specific U5M rate in urban and rural China. METHODS: This population-based epidemiologic study used data obtained by China's National U5M Surveillance System from 1996 to 2013. Data from national surveillance sites were used to examine CA-specific U5M rates by year, urban and rural habitation, and sex. Mixed effect negative binomial regression models were used to assess the trends in CA specific U5M rates and differences in those trends between urban and rural areas. RESULTS: The CA-specific U5M rate decreased from 407.7 per 100,000 live births in 1996 to 217.4 per 100,000 live births in 2013, with average annual decline rates of 6.4% (95% CI=5.6%, 7.1%) and 3.8% (95% CI=3.3%, 4.3%) in urban and rural areas, respectively. The CA-specific U5M rate was the same in both rural and urban areas in 1996, but the U5M rate of the rural areas was 1.621-fold of that of urban areas in 2013. In urban and rural China, cardiovascular anomalies were the most frequent CAs, accounting for 50.3% and 58.2% of U5M due to CA, respectively. CONCLUSIONS: CAs have become one of the leading causes of U5M in both urban and rural China and the difference between the CA-specific U5M rates in two areas is gradually increasing. Reduction of child mortality due to CAs and elimination of the geographic disparity in child mortality rates should be major public health concerns in China. PMID- 26895744 TI - THYROSIM App for Education and Research Predicts Potential Health Risks of Over the-Counter Thyroid Supplements. AB - BACKGROUND: Computer simulation tools for education and research are making increasingly effective use of the Internet and personal devices. To facilitate these activities in endocrinology and metabolism, a mechanistically based simulator of human thyroid hormone and thyrotropin (TSH) regulation dynamics was developed and further validated, and it was implemented as a facile and freely accessible web-based and personal device application: the THYROSIM app. This study elucidates and demonstrates its utility in a research context by exploring key physiological effects of over-the-counter thyroid supplements. METHODS: THYROSIM has a simple and intuitive user interface for teaching and conducting simulated "what-if" experiments. User-selectable "experimental" test-input dosages (oral, intravenous pulses, intravenous infusions) are represented by animated graphical icons integrated with a cartoon of the hypothalamic-pituitary thyroid axis. Simulations of familiar triiodothyronine (T3), thyroxine (T4), and TSH temporal dynamic responses to these exogenous stimuli are reported graphically, along with normal ranges on the same single interface page; and multiple sets of simulated experimental results are superimposable to facilitate comparative analyses. RESULTS AND CONCLUSIONS: This study shows that THYROSIM accurately reproduces a wide range of published clinical study data reporting hormonal kinetic responses to large and small oral hormone challenges. Simulation examples of partial thyroidectomies and malabsorption illustrate typical usage by optionally changing thyroid gland secretion and/or gut absorption rates- expressed as percentages of normal--as well as additions of oral hormone dosing, all directly on the interface, and visualizing the kinetic responses to these challenges. Classroom and patient education usage--with public health implications--is illustrated by predictive simulated responses to nonprescription thyroid health supplements analyzed previously for T3 and T4 content. Notably, it was found that T3 in supplements has potentially more serious pathophysiological effects than does T4--concomitant with low-normal TSH levels. Some preparations contain enough T3 to generate thyrotoxic conditions, with supernormal serum T3 spiking and subnormal serum T4 and TSH levels and, in some cases, with normal or low-normal range TSH levels due to thyroidal axis negative feedback. These results suggest that appropriate regulation of these products is needed. PMID- 26895745 TI - Knowledge of Rabies Prevention in Vietnamese Public Health and Animal Health Workers. AB - Rabies is an invariably fatal, but preventable zoonotic disease. Despite a national programme for its prevention and control, the number of rabies associated deaths in Vietnam has increased in recent years. A cross-sectional survey was undertaken in 2012 to assess and compare the knowledge, awareness and practices of 189 public health workers (PHW) and animal health workers (AHW) attending a joint training course for professionals from provinces in northern Vietnam with the highest number of deaths from rabies. Questionnaires facilitating self-evaluation were provided, and total knowledge scores were calculated (maximum 38 points) and categorized into: 'high' (>30 points), 'moderate' (21-30) and 'low' (<21). The response rate was 100%, and among the 189 participants, 56% were PHW compared to 44% who were AHW. Although most respondents knew rabies could be transmitted through the bite of an animal, most commonly a dog, and that rabies is a preventable disease, significant differences between groups were identified. Major areas included poor knowledge of common rabies reservoirs, wound management and guidance on post-exposure prophylaxis. Overall, the total mean knowledge scores for PHW was significantly higher (P = 0.011) compared to those for AHW, but both scores fell within the 'moderate' knowledge range. However, proportionately more PHW than AHW achieved 'high' knowledge scores (P = 0.0098). To our knowledge this is the first published study to simultaneously assess the knowledge and awareness of animal health and public health professionals attending joint training activities aimed at strengthening rabies prevention and control. To ensure effective prevention and control of rabies requires that AHW and PHW not only coordinate and collaborate, but have a common knowledge and understanding of rabies prevention and control measures. This study provides important baseline data in a relatively unexplored area of research that can focus future interventions and research. PMID- 26895746 TI - Do high numbers of salivary gland-infiltrating B cells predict better or worse outcomes after rituximab in patients with primary Sjogren's syndrome? PMID- 26895747 TI - Subjective visual vertical with the bucket method in Brazilian healthy individuals. AB - INTRODUCTION: The capacity of a healthy individual to estimate the true vertical in relation to the Earth when a fluorescent line is aligned in a completely dark room is called the subjective visual vertical. OBJECTIVE: To evaluate subjective visual vertical using the bucket method in healthy Brazilian individuals. METHODS: Binocular subjective visual vertical was measured in 100 healthy volunteers, 50 females and 50 males. The volunteers indicated the estimated position in which a fluorescent line inside a bucket reached the vertical position. A total of ten repetitions were performed, five clockwise and five counterclockwise. Data were tabulated and analyzed statistically. RESULTS: It was observed that the highest concentration of absolute values of vertical deviation was present up to 3 degrees , regardless of gender, and the vertical deviation did not increase with age. The analysis of the mean of the absolute values of deviations from the vertical of 90% of the sample showed a maximum value of 2.6 degrees , and at the analysis of 95%, the maximum value was 3.4 degrees deviation from the vertical. CONCLUSION: The bucket method is easy to perform and interpret when assessing the deviation of the subjective visual vertical in relation to the true vertical in healthy Brazilian individuals. PMID- 26895748 TI - The Cholinergic Signaling Responsible for the Expression of a Memory-Related Protein in Primary Rat Cortical Neurons. AB - Cholinergic dysfunction in the brain is closely related to cognitive impairment including memory loss. In addition to the degeneration of basal forebrain cholinergic neurons, deficits in the cholinergic receptor signaling may also play an important role. In the present study, to examine the cholinergic signaling pathways responsible for the induction of a memory-related postsynaptic protein, a cholinergic agonist carbachol was used to induce the expression of activity regulated cytoskeleton associated protein (Arc) in primary rat cortical neurons. After pretreating neurons with various antagonists or inhibitors, the levels of carbachol-induced Arc protein expression were detected by Western blot analysis. The results show that carbachol induces Arc protein expression mainly through activating M1 acetylcholine receptors and the downstream phospholipase C pathway, which may lead to the activation of the MAPK/ERK signaling pathway. Importantly, carbachol-mediated M2 receptor activation exerts negative effects on Arc protein expression and thus counteracts the enhanced effects of M1 activation. Furthermore, it is suggested for the first time that M1-mediated enhancement of N methyl-D-aspartate receptor (NMDAR) responses, leading to Ca(2+) entry through NMDARs, contributes to carbachol-induced Arc protein expression. These findings reveal a more complete cholinergic signaling that is responsible for carbachol induced Arc protein expression, and thus provide more information for developing treatments that can modulate cholinergic signaling and consequently alleviate cognitive impairment. J. Cell. Physiol. 231: 2428-2438, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26895749 TI - The Spanish Renal Registry: 2013 report and evolution from 2007-2013. AB - The purpose of the study is to show the evolution of renal replacement therapy (RRT) in Spain from 2007 to 2013. Aggregated data and individual patient records were used from participating regional renal disease registries and that National Transplant Organisation registry. The reference population was the official population on January 1st of each year studied. Data on incidence and prevalence were based on aggregated data, while the survival analysis was calculated from individual patient records. The study period was 2007 to 2013 for prevalence, incidence and transplantation, and survival was analysed for 2004-2012. The population covered by the registry was a minimum of 95.3% to 100% of the Spanish population for aggregated data. The EU27 age and gender distributions of the European population for 2005 were used to adjust incidence and prevalence for age and gender. Survival probabilities were calculated for incident patients between the years 2004 and 2013 using the Kaplan-Meier method to calculate unadjusted patient survival probability. The log rank test was applied to compare survival curves according to some risk factors. Cox proportional hazards model was created to study the potential predictors of survival. In 2013, the total number of patients in Spain that started RRT was 5,705 for 95.3% of the total Spanish population, with an unadjusted rate of 127.1pmp. The evolution from 2007 to 2013 showed a gradual decline from 127.4pmp in 2007 to 120.4pmp in 2012, with a small upturn to 127.1 in 2013. The adjusted incidence rate for the year 2013 was 121.5pmp for the total population, 158.7pmp for males and 83.1pmp for females. The most frequent cause of primary renal disease in incident was diabetes mellitus: 20.4% in 2007, which increased to 24.6% in 2013. The percentage of transplant as first RRT increased from 1.7% in 2007 to 4.2% in 2013. The total number of patients in RRT for 95.3% of the population in 2013 was 50,567, with an unadjusted prevalent rate of 1,125.7pmp. The adjusted prevalence rate for 2013 was 1,087.5 pmp (1,360.7 pmp for males and 809.8pmp for females). The percentage of diabetes mellitus in prevalent patients evolved from 13.9% in 2007 to 14.9% (168 pmp) in 2013. The percentage of transplanted prevalent patients with functioning grafts evolved from 49.3% in 2007 to 51.5% in 2013. The number of transplantations performed each year increased from 2,211 (48.9 pmp) in 2007 (6.2% living donor transplants) to 2,552 (54.2pmp) in 2013 (15.0% living donor transplants). 40,394 patients from 12 regions of Spain who began RRT between 2004 and 2012 were included in the survival analysis (87% Spanish population coverage). Unadjusted patient survival probabilities after one, 2 and 5 years were 91, 81 and 57%, respectively. In the univariate analysis, better survival was found for non-diabetic patients, women, age below 45, peritoneal dialysis as first RRT and patients who had received at least one transplant. PMID- 26895750 TI - Interaction of the Hydrophobic Tip of an Atomic Force Microscope with Oligopeptides Immobilized Using Short and Long Tethers. AB - We report an investigation of the adhesive force generated between the hydrophobic tip of an atomic force microscope (AFM) and surfaces presenting oligopeptides immobilized using either short (~1 nm) or long (~60 nm) tethers. Specifically, we used either sulfosuccinimidyl-4-(N-maleimidomethyl)cyclohexane-1 carboxylate (SSMCC) or 10 kDa polyethylene glycol (PEG) end-functionalized with maleimide and N-hydroxysuccinimide groups to immobilize helical oligomers of beta amino acids (beta-peptides) to mixed monolayers presenting tetraethylene glycol (EG4) and amine-terminated EG4 (EG4N) groups. When SSMCC was used to immobilize the beta-peptides, we measured the adhesive interaction between the AFM tip and surface to rupture through a single event with magnitude consistent with the interaction of a single beta-peptide with the AFM tip. Surprisingly, this occurred even when, on average, multiple beta-peptides were located within the interaction area between the AFM tip and surface. In contrast, when using the long 10 kDa PEG tether, we observed the magnitude of the adhesive interaction as well as the dynamics of the rupture events to unmask the presence of the multiple beta-peptides within the interaction area. To provide insight into these observations, we formulated a simple mechanical model of the interaction of the AFM tip with the immobilized beta-peptides and used the model to demonstrate that adhesion measurements performed using short tethers (but not long tethers) are dominated by the interaction of single beta-peptides because (i) the mechanical properties of the short tether are highly nonlinear, thus causing one beta peptide to dominate the adhesion force at the point of rupture, and (ii) the AFM cantilever is mechanically unstable following the rupture of the adhesive interaction with a single beta-peptide. Overall, our study reveals that short tethers offer the basis of an approach that facilitates measurement of adhesive interactions with single molecules presented at surfaces. PMID- 26895751 TI - Magnetic Technique for Sentinel Lymph Node Biopsy in Melanoma: The MELAMAG Trial. AB - BACKGROUND: Sentinel lymph node biopsy (SLNB) in melanoma is currently performed using the standard dual technique (radioisotope and blue dye). The magnetic technique is non-radioactive and provides a brown color change in the sentinel lymph node (SLN) through an intradermal injection of a magnetic tracer, and utilizes a handheld magnetometer. The MELAMAG Trial compared the magnetic technique with the standard technique for SLNB in melanoma. METHODS: Clinically node-negative patients with primary cutaneous melanoma were recruited from four centers. SLNB was undertaken after intradermal administration of both the standard (blue dye and radioisotope) and magnetic tracers. The SLN identification rate per patient, with the two techniques, was compared. RESULTS: A total of 133 patients were recruited, 129 of which were available for final analysis. The sentinel node identification rate was 97.7 % (126/129) with the standard technique and 95.3 % (123/129) with the magnetic technique [2.3 % difference; 95 % upper confidence limit (CL) 6.4; 5.4 % discordance]. With radioisotope alone, the SLN identification rate was 95.3 % (123/129), as with the magnetic technique (0 % difference; 95 % upper CL 4.5; 7.8 % discordance). The lymph node retrieval rate was 1.99 nodes per patient overall, 1.78 with the standard technique and 1.87 with the magnetic technique. CONCLUSIONS: The magnetic technique is feasible for SLNB in melanoma with a high SLN identification rate, but is associated with skin staining. When compared with the standard dual technique, it did not reach our predefined non-inferiority margin. PMID- 26895752 TI - Voluntary Running Suppresses Tumor Growth through Epinephrine- and IL-6-Dependent NK Cell Mobilization and Redistribution. AB - Regular exercise reduces the risk of cancer and disease recurrence. Yet the mechanisms behind this protection remain to be elucidated. In this study, tumor bearing mice randomized to voluntary wheel running showed over 60% reduction in tumor incidence and growth across five different tumor models. Microarray analysis revealed training-induced upregulation of pathways associated with immune function. NK cell infiltration was significantly increased in tumors from running mice, whereas depletion of NK cells enhanced tumor growth and blunted the beneficial effects of exercise. Mechanistic analyses showed that NK cells were mobilized by epinephrine, and blockade of beta-adrenergic signaling blunted training-dependent tumor inhibition. Moreover, epinephrine induced a selective mobilization of IL-6-sensitive NK cells, and IL-6-blocking antibodies blunted training-induced tumor suppression, intratumoral NK cell infiltration, and NK cell activation. Together, these results link exercise, epinephrine, and IL-6 to NK cell mobilization and redistribution, and ultimately to control of tumor growth. PMID- 26895753 TI - A Body Shape Index and Body Roundness Index: Two new body indices for detecting association between obesity and hyperuricemia in rural area of China. AB - OBJECTIVE: The first objective was to examine whether A Body Shape Index (ABSI) and Body Roundness Index (BRI) can identify hyperuricemia in rural China. The second aim was to compare the relative strength of association between anthropometric indices and hyperuricemia. METHODS: A total of 11,345 participants were involved in this cross-sectional study. Obesity measurements included BMI, WC, WHtR, ABSI and BRI. According to the statistical distribution of serum uric acid (SUA), we split our study population in sex-specific tertiles of SUA. RESULTS: After adjusting for confounding variables, BRI (linear regression: 0.170; AUC: 0.641; OR: 1.459) showed more powerful predictive ability for hyperuricemia than BMI (linear regression: 0.151; AUC: 0.630; OR: 1.108), while having a similar predictive power for hyperuricemia as WHtR (linear regression: 0.191; AUC: 0.656; OR: 1.067) and WC (linear regression: 0.209; AUC: 0.658; OR: 1.047) in the female group, but not in the male group. However, ABSI (A) (linear regression: 0.089 for women, 0.121 for men; AUC: 0.589 for women, 0.578 for men; OR: 1.027 for women, 1.034 for men) and ABSI (B) (linear regression: 0.118 for women, 0.121 for men; AUC: 0.607 for women, 0.578 for men; OR: 1.049 for women, 1.034 for men) had the lowest predictive power for hyperuricemia in both sex categories. CONCLUSIONS: ABSI, BRI, BMI, WC and WHtR were all significantly associated with hyperuricemia in both sexes. In addition, BRI rather than ABSI showed a superior predictive ability for identifying hyperuricemia than BMI in female and similar capabilities as those of WC and WHtR in the female, but not in the male gender. PMID- 26895755 TI - Evaluation of Malignancy Grade of Breast Cancer Using Perflubutane-Enhanced Ultrasonography. AB - Whether the contrast effects of perflubutane on contrast-enhanced ultrasonography can predict the malignancy grade of breast cancer is unknown. We analyzed associations between perfusion parameters created from time-intensity curves based on enhancement intensity and temporal changes in contrast-enhanced ultrasonography and clinicopathologic factors in 100 consecutive patients with invasive breast cancer. Values of perfusion parameters were significantly greater in estrogen receptor-negative than -positive tumors (peak intensity, p = 0.0002; ascending slope, p = 0.006; area under the curve, p = 0.0006). Variations in the peak intensity of Ki-67 were significantly correlated in all tumors (r = 0.54, p < 0.0001) and in luminal (r = 0.43, p = 0.0002), human epidermal growth factor receptor type 2-positive (r = 0.47, p = 0.047) and triple-negative (r = 0.55, p = 0.043) tumors. Perfusion parameters on contrast-enhanced ultrasonography can provide excellent predictive value for high-grade malignancy and might help to determine appropriate therapeutic strategies. PMID- 26895754 TI - Development and Validation of a Method to Measure Lumbosacral Motion Using Ultrasound Imaging. AB - The study aim was to validate an ultrasound imaging technique to measure sagittal plane lumbosacral motion. Direct and indirect measures of lumbosacral angle change were developed and validated. Lumbosacral angle was estimated by the angle between lines through two landmarks on the sacrum and lowest lumbar vertebrae. Distance measure was made between the sacrum and lumbar vertebrae, and angle was estimated after distance was calibrated to angle. This method was tested in an in vitro spine and an in vivo porcine spine and validated to video and fluoroscopy measures, respectively. R(2), regression coefficients and mean absolute differences between ultrasound measures and validation measures were, respectively: 0.77, 0.982, 0.67 degrees (in vitro, angle); 0.97, 0.992, 0.82 degrees (in vitro, distance); 0.94, 0.995, 2.1 degrees (in vivo, angle); and 0.95, 0.997, 1.7 degrees (in vivo, distance). Lumbosacral motion can be accurately measured with ultrasound. This provides a basis to develop measurements for use in humans. PMID- 26895756 TI - Association between Bethesda Categories and Ultrasound Features of Conventional Papillary Thyroid Carcinoma. AB - The association between categories 3, 5 and 6 of the Bethesda System for Reporting Thyroid Cytopathology and the clinical and ultrasonography (US) features of conventional papillary thyroid carcinoma (PTC) was evaluated. We included 2005 patients diagnosed with conventional PTC at surgery and Bethesda categories 3, 5 and 6 at pre-operative US-guided fine-needle aspiration. Multinomial regression analysis was performed to determine the odds ratio (ORs) of each US feature associated with category 3 or 5, with category 6 as reference. Category 3 and 5 PTCs were smaller (ORs = 0.925 and 0.937) and did not exhibit marked hypo-echogenicity (ORs = 0.341 and 0.268) compared with category 6 PTCs. Category 3 and 5 PTCs exhibited significant macrocalcification (ORs = 2.372 and 1.594) and heterogeneous parenchyma (OR = 1.265 in category 5). In conclusion, conventional PTCs pre-operatively aspirated as Bethesda category 3, 5 or 6 significantly differ in size, macrocalcification, underlying thyroid parenchymal echogenicity and final assessment of US features. PMID- 26895757 TI - In vitro analysis of the microbiological sealing of tapered implants after mechanical cycling. AB - OBJECTIVE: The aim of this in vitro study was to evaluate the mechanical behavior and bacterial microleakage at the implant/abutment-tapered interface following mechanical cycling. MATERIALS AND METHODS: Two groups of screwless (Morse taper) implants (G1 and G2) and two groups of prosthetic screwed implants (G3 and G4) were tested. One group from each model (G2 and G4) were submitted to mechanical cycling, 500,000 cycles per sample, at a load of 120 N at 2 Hz prior to analysis. Microbiological analysis was performed via immersion of all samples in an Escherichia coli-containing suspension, incubated at 37 degrees C. After 14 days, the abutments were removed from their respective implants, registering the removal force (G1 and G2) or reverse torque (G3 and G4), and the presence of bacterial leakage was evaluated. Scanning electron microscopy (SEM) was performed to analyze the tapered surfaces of the selected samples. The Student t, binomial, and G tests were used for statistical analysis at a 5 % significance level. RESULTS: The results showed no significant difference between removal force, reverse torque, and contamination values when comparing implants of the same type. However, when the four groups were compared, contamination differed significantly (p = 0.044), with G1 having the least number of contaminated samples (8.3 %). SEM analysis showed superficial defects and damage. CONCLUSIONS: The abutment removal force or torque was not affected by mechanical cycling. Bacterial sealing of the implant/abutment tapered interface was not effective for any condition analyzed. Imprecise machining of implant parts does not allow a sufficient contact area between surfaces to provide effective sealing and prevent bacterial leakage. CLINICAL RELEVANCE: The microscopic gap caused by unsatisfactory implant/abutment adaptation, surface irregularities, and plastic deformation of all parts enabled bacterial contamination of the oral implants. PMID- 26895759 TI - Association between malaria and malnutrition among children aged under-five years in Adami Tulu District, south-central Ethiopia: a case-control study. AB - BACKGROUND: Malaria and malnutrition are the major causes of morbidity and mortality in under-five children in developing countries such as Ethiopia. Malnutrition is the associated cause for about half of the deaths that occur among under-five children in developing countries. However, the relationship between malnutrition and malaria is controversial still, and it has also not been well documented in Ethiopia. The aim of this study was to assess whether malnutrition is associated with malaria among under-five children. METHODS: A case-control study was conducted in Adami Tulu District of East Shewa Zone in Oromia Regional State, Ethiopia. Cases were all under-five children who are diagnosed with malaria at health posts and health centres. The diagnosis was made using either rapid diagnostic tests or microscopy. Controls were apparently healthy under-five children recruited from the community where cases resided. The selection of the controls was based on World Health Organization (WHO) cluster sampling method. A total of 428 children were included. Mothers/caretakers of under-five children were interviewed using pre-tested structured questionnaire prepared for this purpose. The nutritional status of the children was assessed using an anthropometric method and analyzed using WHO Anthro software. A multivariate logistic analysis model was used to determine predictors of malaria. RESULTS: Four hundred twenty eight under-five children comprising 107 cases and 321 controls were included in this study. Prevalence of wasting was higher among cases (17.8%) than the controls (9.3%). Similarly, the prevalence of stunting was 50.5% and 45.2% among cases and controls, respectively. Severe wasting [Adjusted Odds Ratio (AOR) =2.9, 95% CI (1.14, 7.61)] and caretakers who had no education [AOR = 3, 95% CI (1.27, 7.10)] were independently associated with malarial attack among under-five children. CONCLUSION: Children who were severely wasted and had uneducated caretakers had higher odds of malarial attack. Therefore, special attention should be given for severely wasted children in the prevention and control of malaria. PMID- 26895758 TI - The landscape epidemiology of echinococcoses. AB - Echinococcoses are parasitic diseases of major public health importance globally. Human infection results in chronic disease with poor prognosis and serious medical, social and economic consequences for vulnerable populations. According to recent estimates, the geographical distribution of Echinococcus spp. infections is expanding and becoming an emerging and re-emerging problem in several regions of the world. Echinococcosis endemicity is geographically heterogeneous and over time it may be affected by global environmental change. Therefore, landscape epidemiology offers a unique opportunity to quantify and predict the ecological risk of infection at multiple spatial and temporal scales. Here, we review the most relevant environmental sources of spatial variation in human echinococcosis risk, and describe the potential applications of landscape epidemiological studies to characterise the current patterns of parasite transmission across natural and human-altered landscapes. We advocate future work promoting the use of this approach as a support tool for decision-making that facilitates the design, implementation and monitoring of spatially targeted interventions to reduce the burden of human echinococcoses in disease-endemic areas. PMID- 26895760 TI - Daily urinary urea excretion to guide intermittent hemodialysis weaning in critically ill patients. AB - BACKGROUND: There are no easily available markers of renal recovery to guide intermittent hemodialysis (IHD) weaning. The aim of this study was to identify markers for IHD weaning in critically ill patients with acute kidney injury (AKI). METHODS: We performed a retrospective single-center cohort study of patients treated with IHD for at least 7 days and four dialysis sessions for AKI between 2006 and 2011 in an intensive care unit (ICU) of a French university hospital. Blood and urinary markers were recorded on the day of the last IHD in the ICU for unweaned patients and 2 days after the last IHD for weaned patients. Factors associated with IHD weaning were identified by multiple logistic regression. The areas under the receiver operating characteristic curve (AUROC) and the characteristics of the best diagnostic thresholds were compared. RESULTS: Sixty-seven patients were analyzed, including thirty-seven IHD-weaned patients. Urine output [odds ratio (OR) 1.59, 95% confidence interval (CI) 1.20-2.10 (per ml/kg/24 h increase); P = 0.01] and urinary urea concentration [OR 1.29, 95% CI 1.01-1.64 (per 10 mmol/L increase); P = 0.04] were both associated with IHD weaning. The optimal diagnostic thresholds for IHD weaning were urine output greater than 8.5 ml/kg/24 h, urinary urea concentration greater than 148 mmol/L, and daily urea excretion greater than 1.35 mmol/kg/24 h, with accuracy of 82.1%, 76.1%, and 92.5% (P = 0.03), respectively. The AUROC of daily urinary urea excretion (0.96) was greater than the AUROC of urine output (0.86) or the AUROC of urinary urea concentration (0.83) (P < 0.001). CONCLUSIONS: A daily urinary urea excretion greater than 1.35 mmol/kg/24 h was found to be the best marker for weaning ICU patients with AKI from IHD. PMID- 26895762 TI - Osteoblastoma of the maxillary sinus in a child presenting with exophthalmos. AB - INTRODUCTION: Benign osteoblastoma is a rare fibrous bone tumour observed in children. Very few cases involving the paranasal sinuses have been reported. SUMMARY: A 10-year-old child presented with a 1-month history of right exophthalmos. Clinical and radiological assessment demonstrated a heterogeneous tumour with bone components occupying all of the maxillary sinus. Initial histology was in favour of fibrous dysplasia. Surgery was performed via a combined approach. After review of the histology slides, the final diagnosis was that of osteoblastoma. In view of the procedure performed and after consultation, no complementary treatment was proposed. A recurrence was observed 8months later. Right maxillectomy associated with total ethmoidectomy via a combined approach was performed to ensure complete resection of the tumour. A favourable course without recurrence was observed with a follow-up of 5 years. DISCUSSION: Osteoblastoma of the maxillary sinus is rare. CT assessment must be as precise as possible to avoid confusion with another tumour. The diagnosis can only be confirmed by histological examination. This case report is completed by a review of the literature with description of the main differential diagnoses. PMID- 26895761 TI - Associations between proximity to livestock farms, primary health care visits and self-reported symptoms. AB - BACKGROUND: Living in a neighbourhood with a high density of livestock farms has been associated with adverse respiratory health effects, but less is known about healthcare utilisation. This study aimed at investigating the associations between livestock exposure and primary health care visits and self-reported symptoms. In addition, we examined the potentially confounding effect of distance from home to general practice. METHODS: Contact data between 2006 and 2009 were obtained from electronic medical records of 54,777 persons registered within 16 general practices in an area with a high density of livestock farms in the Netherlands. Data on self-reported symptoms were used from a cross-sectional sample of 531 patients in 2010. Livestock presence in a 500 m radius from home was computed using Geographic Information System data. RESULTS: In general, livestock exposure was associated with fewer contacts and self-reported symptoms for respiratory and other conditions. The number of poultry within 500 m was positively associated with the number of contacts. A longer distance to general practice was associated with fewer contacts, but did not confound associations. CONCLUSIONS: People living close to livestock farms less often see their general practitioner and report symptoms. PMID- 26895763 TI - Pulsatile tinnitus and a temporal bone mass. PMID- 26895764 TI - Parathyroid carcinoma presenting as mandibular ulceration. PMID- 26895765 TI - A rare cause of exophthalmos in children. PMID- 26895768 TI - RGB Measurements From Endoscopic Photography as a New and Objective Diagnostic Method for Chronic Tonsillitis. AB - PURPOSE: This study assessed the diagnostic role of a digital photographic assessment of chronic tonsillitis. This study was performed at a tertiary referral center. METHODS: Three cohorts of children were studied based on their diagnoses: current chronic tonsillitis (before tonsillectomy), previous chronic tonsillitis (3 months after tonsillectomy), and healthy children (control group). Oropharyngeal regions of all subjects were examined and photographed endoscopically. Red/green/blue (RGB) values of particular oropharyngeal points were then measured. FINDINGS: The current chronic tonsillitis group differed significantly from the other 2 groups. The RGB values of the current chronic tonsillitis group were significantly higher than those of the previous chronic tonsillitis group (3 months after tonsillectomy) and the control group (P = 0.018 (red), P = 0.024 (green), and P = 0.004 (blue)). The RGB values did not differ significantly between the previous chronic tonsillitis group and the control group (P = 0.684 [red], P = 0.890 [green], and P = 0.672 [blue]). The RGB values of the previous chronic tonsillitis group decreased significantly 3 months after tonsillectomy (P = 0.015 [red], P = 0.033 [green], and P = 0.001 [blue]). Sensitivity was 80%, specificity was 90%, the positive predictive value was 59%, the negative predictive value was 96%, and the general power of the test was 88.6% regarding the power and competence of the RGB test in the diagnosis of chronic tonsillitis. IMPLICATIONS: Measuring RGB values may be an inexpensive and simple way to quickly provide objective and corroborative information on hyperemia of the anterior pillars in diagnosing chronic tonsillitis in conjunction with subjective methods. PMID- 26895769 TI - RELATIONSHIP BETWEEN RADIATION DOSE AND IMAGE QUALITY IN DIGITAL BREAST TOMOSYNTHESIS. AB - This phantom-based study aimed to examine radiation dose from digital breast tomosynthesis (DBT) and digital mammography (DM) and to assess the potential for dose reductions for each modality. Images were acquired at 10-60 mm thicknesses and four dose levels and mean glandular dose was determined using a solid-state dosemeter. Eleven readers assessed image quality and compared simulated lesions with those on a reference image, and the data produced was analysed with the Friedman and Wilcoxon signed-rank tests. For a phantom thickness of 50 mm (typical breast thickness), DBT dose was 13 % higher than DM, but this differential is highly dependent on thickness. Visibility of masses was equal to a reference image (produced at 100 % dose) when dose was reduced by 75 and 50 % for DBT and DM. For microcalcifications, visibility was comparable with the reference image for both modalities at 50 % dose. This study highlighted the potential for reducing dose with DBT. PMID- 26895767 TI - Cardiovascular effects of dapagliflozin in patients with type 2 diabetes and different risk categories: a meta-analysis. AB - BACKGROUND: A pre-specified meta-analysis of cardiovascular (CV) events from 21 phase 2b/3 dapagliflozin clinical trials was undertaken to characterise the CV profile of dapagliflozin. This showed no increase in CV risk with dapagliflozin compared with control (placebo or comparator treatment) with or without background glucose-lowering therapies. The analysis reported here aimed to characterise the CV profile of dapagliflozin in subgroups of patients in these 21 studies grouped by degree of CV risk, based on both baseline and in-study risk factors (including hypoglycaemic events), with a focus on major adverse CV events (MACE). METHODS: Patients with type 2 diabetes, both overall and with different levels of CV risk, including CV disease (CVD) history, age and other CV risk factors, were analysed. A further analysis compared CV risk in patients who experienced a hypoglycaemic event prior to MACE and those who did not. Analyses were based on time to first event using a Cox proportional hazards model stratified by study comparing dapagliflozin versus control. RESULTS: In total, 9339 patients were included in this meta-analysis; 5936 patients received dapagliflozin 2.5-10 mg (6668 patient-years) and 3403 received control (3882 patient-years). Dapagliflozin is not associated with increased CV risk and results further suggest the potential for a beneficial effect both in the overall population [Hazard Ratio (HR) 0.77; 95 % CI (0.54, 1.10) for MACE] and in those with a history of CVD [HR 0.80 (0.53, 1.22)]. These findings were consistent in patients with varying degrees of CV risk, including age, number and type of CVD events in medical history and number of CV risk factors present. Furthermore, there was no increased risk of MACE in patients who experienced a hypoglycaemic event compared with those who did not. CONCLUSIONS: There was no suggestion of increased risk for MACE with dapagliflozin compared with control in any of the populations investigated. In addition, the results suggest the potential for a beneficial CV effect which is consistent with the multifactorial benefits on CV risk factors associated with sodium-glucose cotransporter-2 (SGLT2) inhibitors. PMID- 26895771 TI - Antimicrobial allergy 'labels' drive inappropriate antimicrobial prescribing: lessons for stewardship. AB - BACKGROUND: The presence of antimicrobial allergy designations ('labels') often substantially reduces prescribing options for affected patients, but the frequency, accuracy and impacts of such labels are unknown. METHODS: The National Antimicrobial Prescribing Survey (NAPS) is an annual de-identified point prevalence audit of Australian inpatient antimicrobial prescribing using standardized definitions of guideline compliance, appropriateness and indications. Data were extracted for 2 years (2013-14) and compared for patients with an antimicrobial allergy label (AAL) and with no AAL (NAAL). RESULTS: Among 21 031 patients receiving antimicrobials (33 421 prescriptions), an AAL was recorded in 18%, with inappropriate antimicrobial use significantly higher in the AAL group versus the NAAL group (OR 1.12, 95% CI 1.05-1.22, P < 0.002). Patterns of antimicrobial use were significantly influenced by AAL, with lower beta-lactam use (AAL versus NAAL; OR 0.47, 95% CI 0.43-0.50, P < 0.001) and higher quinolone (OR 2.07, 95% CI 1.83-2.34, P < 0.0001), glycopeptide (OR 1.59, 95% CI 1.38-1.83, P < 0.0001) and carbapenem (OR 1.74, 95% CI 1.43-2.13, P < 0.0001) use. In particular, among immunocompromised patients, AAL was associated with increased rates of inappropriate antimicrobial use (OR 1.68, 95% CI 1.21-2.30, P = 0.003), as well as increased use of quinolones (OR 1.88, 95% CI 1.16-3.03, P = 0.02) and glycopeptides (OR 1.82, 95% CI 1.17-2.84, P = 0.01). CONCLUSIONS: AALs are common and appear to be associated with higher rates of inappropriate prescribing and increased use of broad-spectrum antimicrobials. Improved accuracy in defining AALs is likely to be important for effective antimicrobial stewardship (AMS), with efforts to 'de-label' inappropriate AAL patients a worthwhile feature of future AMS initiatives. PMID- 26895770 TI - Electroacupuncture improves memory and protects neurons by regulation of the autophagy pathway in a rat model of Alzheimer's disease. AB - BACKGROUND: Acupuncture is a potential therapy for Alzheimer's disease (AD), but its clinical effects and underlying mechanisms are not fully understood. Emerging evidence suggests autophagy is involved in beta-amyloid (Abeta) clearance. We hypothesised that electroacupuncture (EA) treatment of AD involves the autophagy pathway in rats. METHODS: We injected 2MUl Abeta1-40 bilaterally into the hippocampi of 42 rats to establish AD. Rats remained untreated (AD group, n=14) or received 24 EA treatments at GV20+BL23 over 28 days from day 7 post-injection with/without co-treatment with 3-methyladenine (3-MA), an autophagy inhibitor (AD+EA+3-MA and AD+EA groups, respectively, n=14 each). Cognitive function was evaluated by Morris water maze (MWM) testing. Hippocampi were examined by transmission electron microscopy (TEM) and stained with haematoxylin and eosin/transferase dUTP nick end labelling (TUNEL) to assess neuronal morphology/apoptosis, respectively. Protein expression of Beclin-1, LC3 and Abeta1-40 was examined. RESULTS: In the MWM test, the AD+EA group showed an improvement in parameters consistent with improved learning/memory compared to untreated AD rats, and 3-MA attenuated these effects. EA mitigated cellular apoptosis resulting from Abeta infusion in the CA1 region and enhanced LC3II/LC3I ratios and Beclin-1 expression. Numerous autophagosome precursors and enlarged autophagosomes were observed by TEM in the hippocampi of EA-treated rats. Reduced Abeta levels, and co-localisation of Abeta and LC3II, were observed following EA treatment by immunofluorescence staining. EA+3-MA treated rats had much higher TUNEL-positive neurons, lower LC3II/LC3I ratios and Beclin-1 expression, and elevated Abeta levels compared with EA alone. CONCLUSIONS: EA reduces neuronal apoptosis, enhances degradation of Abeta, and improves learning/memory in AD rats by upregulating the autophagy pathway. PMID- 26895766 TI - Targeting the Metastasis Suppressor, N-Myc Downstream Regulated Gene-1, with Novel Di-2-Pyridylketone Thiosemicarbazones: Suppression of Tumor Cell Migration and Cell-Collagen Adhesion by Inhibiting Focal Adhesion Kinase/Paxillin Signaling. AB - Metastasis is a complex process that is regulated by multiple signaling pathways, with the focal adhesion kinase (FAK)/paxillin pathway playing a major role in the formation of focal adhesions and cell motility. N-myc downstream regulated gene-1 (NDRG1) is a potent metastasis suppressor in many solid tumor types, including prostate and colon cancer. Considering the antimetastatic effect of NDRG1 and the crucial involvement of the FAK/paxillin pathway in cellular migration and cell matrix adhesion, we assessed the effects of NDRG1 on this important oncogenic pathway. In the present study, NDRG1 overexpression and silencing models of HT29 colon cancer and DU145 prostate cancer cells were used to examine the activation of FAK/paxillin signaling and the formation of focal adhesions. The expression of NDRG1 resulted in a marked and significant decrease in the activating phosphorylation of FAK and paxillin, whereas silencing of NDRG1 resulted in an opposite effect. The expression of NDRG1 also inhibited the formation of focal adhesions as well as cell migration and cell-collagen adhesion. Incubation of cells with novel thiosemicarbazones, namely di-2-pyridylketone 4,4-dimethyl-3 thiosemicarbazone and di-2-pyridylketone 4-cyclohexyl-4-methyl-3 thiosemicarbazone, that upregulate NDRG1 also resulted in decreased phosphorylation of FAK and paxillin. The ability of these thiosemicarbazones to inhibit cell migration and metastasis could be mediated, at least in part, through the FAK/paxillin pathway. PMID- 26895773 TI - The heterogeneity of attention-deficit/hyperactivity disorder symptoms and conduct problems: Cognitive inhibition, emotion regulation, emotionality, and disorganized attachment. AB - This study examined the contributions of several important domains of functioning to attention-deficit/hyperactivity disorder (ADHD) symptoms and conduct problems. Specifically, we investigated whether cognitive inhibition, emotion regulation, emotionality, and disorganized attachment made independent and specific contributions to these externalizing behaviour problems from a multiple pathways perspective. The study included laboratory measures of cognitive inhibition and disorganized attachment in 184 typically developing children (M age = 6 years, 10 months, SD = 1.7). Parental ratings provided measures of emotion regulation, emotionality, and externalizing behaviour problems. Results revealed that cognitive inhibition, regulation of positive emotion, and positive emotionality were independently and specifically related to ADHD symptoms. Disorganized attachment and negative emotionality formed independent and specific relations to conduct problems. Our findings support the multiple pathways perspective on ADHD, with poor regulation of positive emotion and high positive emotionality making distinct contributions to ADHD symptoms. More specifically, our results support the proposal of a temperamentally based pathway to ADHD symptoms. The findings also indicate that disorganized attachment and negative emotionality constitute pathways specific to conduct problems rather than to ADHD symptoms. PMID- 26895772 TI - Impact on toxin production and cell morphology in Clostridium difficile by ridinilazole (SMT19969), a novel treatment for C. difficile infection. AB - OBJECTIVES: Ridinilazole (SMT19969) is a narrow-spectrum, non-absorbable antimicrobial with activity against Clostridium difficile undergoing clinical trials. The purpose of this study was to assess the pharmacological activity of ridinilazole and assess the effects on cell morphology. METHODS: Antibiotic killing curves were performed using the epidemic C. difficile ribotype 027 strain, R20291, using supra-MIC (4* and 40*) and sub-MIC (0.125*, 0.25* and 0.5*) concentrations of ridinilazole. Following exposure, C. difficile cells were collected for cfu counts, toxin A and B production, and morphological changes using scanning electron and fluorescence microscopy. Human intestinal cells (Caco 2) were co-incubated with ridinilazole-treated C. difficile growth medium to determine the effects on host inflammatory response (IL-8). RESULTS: Treatment at supra-MIC concentrations (4* and 40* MIC) of ridinilazole resulted in a significant reduction in vegetative cells over 72 h (4 log difference, P < 0.01) compared with controls without inducing spore formation. These results correlated with a 75% decrease in toxin A production (P < 0.05) and a 96% decrease in toxin B production (P < 0.05). At sub-MIC levels (0.5* MIC), toxin A production was reduced by 91% (P < 0.01) and toxin B production was reduced by 100% (P < 0.001), which resulted in a 74% reduction in IL-8 release compared with controls (P < 0.05). Sub-MIC (0.5*)-treated cells formed filamentous structures ~10-fold longer than control cells. Following fluorescence labelling, the cell septum was not forming in sub-MIC-treated cells, yet the DNA was dividing. CONCLUSIONS: Ridinilazole had robust killing effects on C. difficile that significantly reduced toxin production and attenuated the inflammatory response. Ridinilazole also elicited significant cell division effects suggesting a potential mechanism of action. PMID- 26895774 TI - The final twist: the use of a wound protector in reducing an extracorporeal anastomosis - a video vignette. PMID- 26895775 TI - How Long Did You Look At Me? The Influence of Gaze Direction on Perceived Duration and Temporal Sensitivity. AB - Faces that exhibit emotionally negative expressions in mutual gaze have been shown to induce a dilation of perceived duration. The influence of gaze by itself on duration judgments, however, has rarely been investigated. We argue for a social interaction hypothesis, according to which humans should be highly accurate and precise (sensitive) when processing the temporal dynamics of mutual gaze. In three experiments, we investigated whether the direction of observed gaze affects perceived duration and temporal sensitivity. In Experiment 1, subjects did indeed estimate the duration of direct gaze more accurately as compared to the duration of averted gaze. In Experiments 2 and 3, subjects had to categorize direct and averted gaze stimuli as being short or long in duration (temporal bisection). Experiment 2 found temporal sensitivity (but not mean duration judgments) to be improved in cases of mutual gaze. In Experiment 3, the effect of mutual gaze on prolonged subjective duration did replicate, however, it was rather small. Moreover, temporal precision was not improved in the case of naturalistic stimuli. In sum, effects of mutual gaze on duration judgments are rather weak, and cannot be attributed to arousal, as such ratings did not differ between direct and averted gaze stimuli. PMID- 26895776 TI - A Novel Electronic Medical Record-Based Workflow to Measure and Report Colonoscopy Quality Measures. PMID- 26895777 TI - Effects of cisplatin chemotherapy on the osseointegration of titanium implants. AB - PURPOSE: The effect of chemotherapy on the osseointegration of dental implants has received less interest compared with radiotherapy. Thus, the aim of the current study was to investigate the effect of cisplatin chemotherapy on the osseointegration of dental implants in a rabbit model. MATERIALS AND METHODS: Sixteen New Zealand White rabbits were randomly assigned to two groups of treatment of either cisplatin at 2.5 mg/kg/week for 4 weeks (n = 8) or placebo (n = 8), in which the first dose was administered 2 days prior to the surgical procedure. Each rabbit received one titanium dental implant inserted in the right distal femoral condyle. Four rabbits from each group were sacrificed 4 and 8 weeks after implant insertion. Osseointegration of the dental implants was analysed using micro-computed tomography and histomorphometric evaluation. RESULTS: Analysis of micro-computed tomography data and histomorphometric data showed that the osseointegration parameters, including the ratio of bone volume to total volume (BV/TV) and bone-implant contact (BIC%) for the cisplatin group, were significantly lower compared to the control group at 4 and 8 weeks. (P <= 0.05). CONCLUSION: Cisplatin chemotherapy had a negative effect on the osseointegration of dental implants when inserted throughout the chemotherapeutic regimens in a rabbit model. PMID- 26895778 TI - Global trends in myopia management attitudes and strategies in clinical practice. AB - PURPOSE: Myopia is a global public health issue; however, no information exists as to how potential myopia retardation strategies are being adopted globally. METHODS: A self-administrated, internet-based questionnaire was distributed in six languages, through professional bodies to eye care practitioners globally. The questions examined: awareness of increasing myopia prevalence, perceived efficacy and adoption of available strategies, and reasons for not adopting specific strategies. RESULTS: Of the 971 respondents, concern was higher (median 9/10) in Asia than in any other continent (7/10, p<0.001) and they considered themselves more active in implementing myopia control strategies (8/10) than Australasia and Europe (7/10), with North (4/10) and South America (5/10) being least proactive (p<0.001). Orthokeratology was perceived to be the most effective method of myopia control, followed by increased time outdoors and pharmaceutical approaches, with under-correction and single vision spectacles felt to be the least effective (p<0.05). Although significant intra-regional differences existed, overall most practitioners 67.5 (+/-37.8)% prescribed single vision spectacles or contact lenses as the primary mode of correction for myopic patients. The main justifications for their reluctance to prescribe alternatives to single vision refractive corrections were increased cost (35.6%), inadequate information (33.3%) and the unpredictability of outcomes (28.2%). CONCLUSIONS: Regardless of practitioners' awareness of the efficacy of myopia control techniques, the vast majority still prescribe single vision interventions to young myopes. In view of the increasing prevalence of myopia and existing evidence for interventions to slow myopia progression, clear guidelines for myopia management need to be established. PMID- 26895779 TI - Numerical simulation of the damage evolution in the pelvic floor muscles during childbirth. AB - Several studies have shown that pelvic floor injuries during a vaginal delivery can be considered a significant factor in the development of pelvic floor dysfunction. Such disorders include a group of conditions affecting women like urinary incontinence, pelvic organ prolapse and fecal incontinence. Numerical simulations are valuable tools that are contributing to the clarification of the mechanisms behind pelvic floor disorders. The aim of this work is to propose a mechanical model implemented in the finite element method context to estimate the damage in the pelvic floor muscles by mechanical effects during a vaginal delivery of a fetus in vertex presentation and occipitoanterior position. The constitutive model adopted has already been successfully used in the simulation of childbirth and the structural damage model added has previously been applied to characterize the damage process in biological soft tissues undergoing finite deformations. The constitutive parameters were fit to experimental data available in the literature and the final proposed material model is suitable to estimate the mechanical damage in the pelvic floor muscle during a vaginal delivery. The computational model predicts that even an apparently uneventful vaginal delivery inflicts injuries to the pelvic floor muscles, particularly during the extension of the fetus head, having been obtained more than 10% of damaged fibers. As a clinical evidence, the present work allows to conclude that the puborectalis component of the levator ani muscle is the most prone to damage. PMID- 26895781 TI - Atrial systole enhances intraventricular filling flow propagation during increasing heart rate. AB - Diastolic fluid dynamics in the left ventricle (LV) has been examined in multiple clinical studies for understanding cardiac function in healthy humans and developing diagnostic measures in disease conditions. The question of how intraventricular filling vortex flow pattern is affected by increasing heart rate (HR) is still unanswered. Previous studies on healthy subjects have shown a correlation between increasing HR and diminished E/A ratio of transmitral peak velocities during early filling (E-wave) to atrial systole (A-wave). We hypothesize that with increasing HR under constant E/A ratio, E-wave contribution to intraventricular vortex propagation is diminished. A physiologic in vitro flow phantom consisting of a LV physical model was used for this study. HR was varied across 70, 100 and 120 beats per minute (bpm) with E/A of 1.1-1.2. Intraventricular flow patterns were characterized using 2D particle image velocimetry measured across three parallel longitudinal (apical-basal) planes in the LV. A pair of counter-rotating vortices was observed during E-wave across all HRs. With increasing HR, diminished vortex propagation occurred during E-wave and atrial systole was found to amplify secondary vorticity production. The diastolic time point where peak vortex circulation occurred was delayed with increasing HR, with peak circulation for 120bpm occurring as late as 90% into diastole near the end of A-wave. The role of atrial systole is elevated for higher HR due to the limited time available for filling. Our baseline findings and analysis approach can be applied to studies of clinical conditions where impaired exercise tolerance is observed. PMID- 26895782 TI - Optimal management of distal ureteric strictures following renal transplantation: a systematic review. AB - Our objective was to define optimal management of distal ureteric strictures following renal transplantation. A systematic review on PubMed identified 34 articles (385 patients). Primary endpoints were success rates and complications of specific primary and secondary treatments (following failure of primary treatment). Among primary treatments (n = 303), the open approach had 85.4% success (95% CI 72.5-93.1) and the endourological approach had 64.3% success (95% CI 58.3-69.9). Among secondary treatments (n = 82), the open approach had 93.1% success (95% CI 77.0-99.2) and the endourological approach had 75.5% success (95% CI 62.3-85.2). The most common primary open treatment was ureteric reimplantation (n = 33, 81.8% success, 95% CI 65.2-91.8). The most common primary endourological treatment was dilation (n = 133, 58.6% success, 95% CI 50.1-66.7). Fourteen complications, including death (4 weeks post-op) and graft loss (12 days post op), followed endourological treatment. One complication followed open treatment. This is the first systematic review to examine the success rates and complications of specific treatments for distal ureteric strictures following renal transplantation. Our review indicates that open management has higher success rates and fewer complications than endourological management as a primary and secondary treatment for post-transplant distal ureteric strictures. We also outline a post-transplant ureteric stricture evaluation and treatment algorithm. PMID- 26895780 TI - A puzzle assembly strategy for fabrication of large engineered cartilage tissue constructs. AB - Engineering of large articular cartilage tissue constructs remains a challenge as tissue growth is limited by nutrient diffusion. Here, a novel strategy is investigated, generating large constructs through the assembly of individually cultured, interlocking, smaller puzzle-shaped subunits. These constructs can be engineered consistently with more desirable mechanical and biochemical properties than larger constructs (~4-fold greater Young's modulus). A failure testing technique was developed to evaluate the physiologic functionality of constructs, which were cultured as individual subunits for 28 days, then assembled and cultured for an additional 21-35 days. Assembled puzzle constructs withstood large deformations (40-50% compressive strain) prior to failure. Their ability to withstand physiologic loads may be enhanced by increases in subunit strength and assembled culture time. A nude mouse model was utilized to show biocompatibility and fusion of assembled puzzle pieces in vivo. Overall, the technique offers a novel, effective approach to scaling up engineered tissues and may be combined with other techniques and/or applied to the engineering of other tissues. Future studies will aim to optimize this system in an effort to engineer and integrate robust subunits to fill large defects. PMID- 26895783 TI - Evaluation of Factors Affecting Acute Postoperative Pain Levels After Arthroscopic Rotator Cuff Repair. AB - PURPOSE: To evaluate multiple preoperative and operative factors that may be predictive of and correlate with acute postoperative pain levels after arthroscopic rotator cuff repair. METHODS: One hundred eighty-one patients underwent arthroscopic rotator cuff surgery along with subacromial decompression and met the inclusion criteria for this study. Postoperative visual analog scale (VAS) scores were obtained on postoperative days 1, 7, and 90. Multivariate linear regression analysis was used to correlate postoperative VAS scores with multiple independent factors, including preoperative subjective pain tolerance, preoperative VAS score, preoperative narcotic use, sex, smoking status, number of suture anchors used, tear size, single- or double-row repair, and patient age. RESULTS: Preoperative subjective pain tolerance, notably those patients rating themselves as having an extremely high pain tolerance, was the most significant predictor of high VAS pain scores on both postoperative day 1 (P = .0001) and postoperative day 7 (P < .0001). Preoperative narcotic use was also significantly predictive (P = .010) of high pain scores on postoperative day 1 and day 7 (P = .019), along with nonsmokers (P = .008) and younger patients (P = .006) being predictive on day 7. There were no patient factors that were predictive of VAS scores 3 months postoperatively (P = .567). CONCLUSIONS: Preoperative subjective pain tolerance, notably those patients rating themselves as having an extremely high pain tolerance, was the strongest factor predicting high acute pain levels after arthroscopic rotator cuff surgery. Preoperative narcotic use, smokers, and younger patients were also predictive of higher pain levels during the first postoperative week. LEVEL OF EVIDENCE: Level IV, prognostic case series. PMID- 26895784 TI - The Effects of Arthroscopic Lateral Acromioplasty on the Critical Shoulder Angle and the Anterolateral Deltoid Origin: An Anatomic Cadaveric Study. AB - PURPOSE: To investigate if (1) an anterolateral acromioplasty and (2) a lateral acromion resection alter the critical shoulder angle (CSA) without affecting the deltoid origin. METHODS: First, the native CSAs of 10 human cadaveric shoulders (6 male and 4 female specimens; mean age, 54.2 years) were determined with the use of fluoroscopy. Setup allowed for consistent repetitive measurements. Next, a standard arthroscopic anterolateral acromioplasty was performed to create a type 1 acromion, and the CSA was reassessed fluoroscopically. Afterward, a lateral acromioplasty was performed with a 5-mm lateral acromion resection using a 5-mm burr, and the CSA was measured again. The native CSA was compared with (1) the CSA after acromioplasty and (2) the CSA after acromioplasty and lateral acromion resection using a paired t test. Finally, the acromial deltoid attachment was evaluated anatomically for damage to the anterolateral origin. RESULTS: The mean native CSA (34.3 degrees +/- 2.1 degrees ) was reduced significantly by acromioplasty (33.1 degrees +/- 2.0 degrees , P < .001) and further reduced by lateral acromion resection (31.5 degrees +/- 1.7 degrees , P < .001). Anterolateral acromioplasty reduced the CSA by a mean of 1.4 degrees (95% confidence interval boundaries, 0.8 degrees and 1.9 degrees ), and in combination with lateral acromion resection, the CSA was reduced by a mean of 2.8 degrees (95% confidence interval boundaries, 2.1 degrees and 3.5 degrees ). In all specimens (5 of 5) with a presurgery CSA of 35 degrees or greater, the CSA was reduced to the range of 30 degrees to 35 degrees by the combination of both techniques. However, in 2 specimens with a CSA of approximately 32 degrees , the CSA was reduced to less than 30 degrees . The acromial deltoid attachment was found to be well preserved in all specimens. CONCLUSIONS: Arthroscopic anterolateral acromioplasty and a 5-mm lateral acromion resection each reduced the CSA significantly and did not damage the deltoid origin. CLINICAL RELEVANCE: The combination of both techniques could potentially be used in clinical practice to reduce a CSA greater than 35 degrees to the desired range of 30 degrees to 35 degrees . PMID- 26895785 TI - Biomechanical Evaluation of Suture Anchor Versus Transosseous Tunnel Quadriceps Tendon Repair Techniques. AB - PURPOSE: To evaluate the biomechanical fixation strength of suture anchor and transosseous tunnel repair of the quadriceps tendon in a standardized cadaveric repair model. METHODS: Twelve "patella-only" specimens were used. Dual-energy X ray absorptiometry measurement was performed to ensure equal bone quality amongst groups. Specimens were randomly assigned to either a suture anchor repair of quadriceps tendon group (n = 6) or a transosseous tunnel repair group (n = 6). Suture type and repair configuration were equivalent. After the respective procedures were performed, each patella was mounted into a gripping jig. Tensile load was applied at a rate of 0.1 mm/s up to 100 N after which cyclic loading was applied at a rate of 1 Hz between magnitudes of 50 to 150 N, 50 to 200 N, 50 to 250 N, and tensile load at a rate of 0.1 mm/s until failure. Outcome measures included load to failure, displacement at 1st 100 N load, and displacement after each 10th cycle of loading. RESULTS: The measured cyclic displacement to the first 100 N, 50 to 150 N, 50 to 200 N, and 50 to 250 N was significantly less for suture anchors than transosseous tunnels. There was no statistically significant difference in ultimate load to failure between the 2 groups (P = .40). Failure mode for all suture anchors except one was through the soft tissue. Failure mode for all transosseous specimens but one was pulling the repair through the transosseous tunnel. CONCLUSIONS: Suture anchor quadriceps tendon repairs had significantly decreased gapping during cyclic loading, but no statistically significant difference in ultimate load to failure when compared with transosseous tunnel repairs. Although suture anchor quadriceps tendon repair appears to be a biomechanically superior construct, a clinical study is needed to confirm this technique as a viable alternative to gold standard transosseous techniques. CLINICAL RELEVANCE: Although in vivo studies are needed, these results support the suture anchor technique as a viable alternative to transosseous repair of the quadriceps tendon. PMID- 26895786 TI - Novel customized template designing for patellar resurfacing in total knee arthroplasty. AB - : Due to the irregular shape of patella and difficulty in identifying its bony landmarks, it can be a challenge for surgeons to accurately and symmetrically perform patellar resurfacing. Three-dimensional (3D) models of 20 patellae were generated from computed tomographic images. Using a computer-assisted preoperative planning technique, customized template designs were developed to guide patellar resurfacing. The patellar models and corresponding templates were produced through rapid prototyping. The accuracy of this technique was assessed after applying the templates on patellar models and cadaver specimens, respectively. Using preoperative planning and predesigned templates, a significant improvement in symmetric patellar resurfacing, with a mean angle of 1.21 degrees mediolateral (ML) obliquity and 1.95 degrees superoinferior (SI) obliquity, was observed compared with the conventional sawguide technique (mean angle of ML and SI was 4.13 degrees , 4.95 degrees , respectively). Additionally, the use of customized templates reproduced the desired preplanned patellar resection. Preoperative planning with 3D imaging and customized templates improved the accuracy of patellar resurfacing in terms of the obliquity and thickness. CLINICAL RELEVANCE: A novel customized template designed for patellar resectioning will benefit surgeons in performing patellar resurfacing. This technique will provide accurate patellar resurfacing in clinical practice. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1798-1803, 2016. PMID- 26895787 TI - Involvement of Aif1 in apoptosis triggered by lack of Hxk2 in the yeast Saccharomyces cerevisiae. AB - We recently showed that in hxk2Delta cells, showing constitutive localization of active Ras at the mitochondria, addition of acetic acid caused an increase of both apoptotic and necrotic cells compared with the wild-type strain, providing a new role for hexokinase 2 (EC 2.7.1.1) as an anti-apoptotic factor, besides its known role as a glycolytic enzyme and as a regulator of gene transcription of several Mig1-regulated genes. We also demonstrated that apoptosis induced by lack of Hxk2 may not require the activation of Yca1. Here, we show that deletion of HXK2 causes hypersensitivity to H2O2 and that addition of this well-known apoptotic stimulus to hxk2Delta cells causes an increase in the level ROS, apoptosis and mitochondrial membrane potential. We also show that deletion of AIF1 in hxk2Delta cells enhances survival after induction of apoptosis with both H2O2 and acetic acid, rescues the reduction of both growth rate and cell size, abrogates both H2O2 and acetic acid-induced ROS accumulation and decreases cell death, suggesting that Aif1 might be involved in both H2O2 and acetic acid induced cell death in hxk2Delta cells. Moreover, we show that active Ras proteins relocalize to the plasma membrane and to the nucleus in hxk2Delta aif1Delta cells. PMID- 26895789 TI - A Comparison of Maternal versus Paternal Nonverbal Behavior During Child Pain. AB - Parental behavior plays a significant role in children's pain response. Prior research has found generally no differences between mothers' and fathers' verbal behavior during child pain. This study compared mothers' and fathers' nonverbal behavior during child pain. Nonverbal behavior of mothers (n = 39) and fathers (n = 39) of 39 children (20 boys) aged 8 to 12 years who participated in the cold pressor task (counterbalanced once with each parent) was coded. A range of nonverbal behaviors were coded, including distraction, physical proximity, physical comfort/reassurance, procedure-related attending behavior, and fidgeting. The most common behaviors parents engaged in were fidgeting, procedure related attending behaviors, and physical proximity. Results indicated that the types of nonverbal behavior parents engage in did not differ between mothers and fathers. However, children of mothers who engaged in more physical comfort/reassurance reported higher levels of pain intensity, and children of mothers who engaged in more procedure-related attending behaviors had lower pain tolerance. Further, both mothers and fathers who engaged in higher levels of verbal nonattending behaviors also engaged in lower levels of nonverbal procedure related attending behaviors. These findings further support the importance of considering the influence of mothers and fathers in children's pain, and provide novel insights into the role of nonverbal behavior. PMID- 26895790 TI - Sugar tax could stop 3.7 million UK people becoming obese, claims report. PMID- 26895788 TI - Alternative reactions at the interface of glycolysis and citric acid cycle in Saccharomyces cerevisiae. AB - Pyruvate and acetyl-coenzyme A, located at the interface between glycolysis and TCA cycle, are important intermediates in yeast metabolism and key precursors for industrially relevant products. Rational engineering of their supply requires knowledge of compensatory reactions that replace predominant pathways when these are inactivated. This study investigates effects of individual and combined mutations that inactivate the mitochondrial pyruvate-dehydrogenase (PDH) complex, extramitochondrial citrate synthase (Cit2) and mitochondrial CoA-transferase (Ach1) in Saccharomyces cerevisiae. Additionally, strains with a constitutively expressed carnitine shuttle were constructed and analyzed. A predominant role of the PDH complex in linking glycolysis and TCA cycle in glucose-grown batch cultures could be functionally replaced by the combined activity of the cytosolic PDH bypass and Cit2. Strongly impaired growth and a high incidence of respiratory deficiency in pda1Delta ach1Delta strains showed that synthesis of intramitochondrial acetyl-CoA as a metabolic precursor requires activity of either the PDH complex or Ach1. Constitutive overexpression of AGP2, HNM1, YAT2, YAT1, CRC1 and CAT2 enabled the carnitine shuttle to efficiently link glycolysis and TCA cycle in l-carnitine-supplemented, glucose-grown batch cultures. Strains in which all known reactions at the glycolysis-TCA cycle interface were inactivated still grew slowly on glucose, indicating additional flexibility at this key metabolic junction. PMID- 26895791 TI - Brain Insulin Signaling Is Increased in Insulin-Resistant States and Decreases in FOXOs and PGC-1alpha and Increases in Abeta1-40/42 and Phospho-Tau May Abet Alzheimer Development. AB - Increased coexistence of Alzheimer disease (AD) and type 2 diabetes mellitus (T2DM) suggests that insulin resistance abets neurodegenerative processes, but linkage mechanisms are obscure. Here, we examined insulin signaling factors in brains of insulin-resistant high-fat-fed mice, ob/ob mice, mice with genetically impaired muscle glucose transport, and monkeys with diet-dependent long-standing obesity/T2DM. In each model, the resting/basal activities of insulin-regulated brain protein kinases, Akt and atypical protein kinase C (aPKC), were maximally increased. Moreover, Akt hyperactivation was accompanied by hyperphosphorylation of substrates glycogen synthase kinase-3beta and mammalian target of rapamycin and FOXO proteins FOXO1, FOXO3A, and FOXO4 and decreased peroxisome proliferator activated receptor gamma coactivator-1alpha (PGC-1alpha) expression. Akt hyperactivation was confirmed in individual neurons of anterocortical and hippocampal regions that house cognition/memory centers. Remarkably, beta-amyloid (Abeta1-40/42) peptide levels were as follows: increased in the short term by insulin in normal mice, increased basally in insulin-resistant mice and monkeys, and accompanied by diminished amyloid precursor protein in monkeys. Phosphorylated tau levels were increased in ob/ob mice and T2DM monkeys. Importantly, with correction of hyperinsulinemia by inhibition of hepatic aPKC and improvement in systemic insulin resistance, brain insulin signaling normalized. As FOXOs and PGC-1alpha are essential for memory and long-term neuronal function and regeneration and as Abeta1-40/42 and phospho-tau may increase interneuronal plaques and intraneuronal tangles, presently observed aberrations in hyperinsulinemic states may participate in linking insulin resistance to AD. PMID- 26895792 TI - Risk Factors for Cardiovascular Disease in Type 1 Diabetes. AB - Risk factors for cardiovascular disease (CVD) are well-established in type 2 but not type 1 diabetes (T1DM). We assessed risk factors in the long-term (mean 27 years) follow-up of the Diabetes Control and Complications Trial (DCCT) cohort with T1DM. Cox proportional hazards multivariate models assessed the association of traditional and novel risk factors, including HbA1c, with major atherosclerotic cardiovascular events (MACE) (fatal or nonfatal myocardial infarction [MI] or stroke) and any-CVD (MACE plus confirmed angina, silent MI, revascularization, or congestive heart failure). Age and mean HbA1c were strongly associated with any-CVD and with MACE. For each percentage point increase in mean HbA1c, the risk for any-CVD and for MACE increased by 31 and 42%, respectively. CVD and MACE were associated with seven other conventional factors, such as blood pressure, lipids, and lack of ACE inhibitor use, but not with sex. The areas under the receiver operating characteristics curves for the association of age and HbA1c, taken together with any-CVD and for MACE, were 0.70 and 0.77, respectively, and for the final models, including all significant risk factors, were 0.75 and 0.82. Although many conventional CVD risk factors apply in T1DM, hyperglycemia is an important risk factor second only to age. PMID- 26895794 TI - Epidemiology of Toxocariasis in England and Wales. AB - Toxocara infection occurs through ingestion of parasite eggs excreted by dogs and cats, and can cause severe morbidity. The burden of disease in England and Wales is not well described, and the impact of public health campaigns conducted in the mid-1990s is uncertain. This paper uses data from two extensive databases to explore the trends in this disease in England and Wales from the 1970s to 2009. PMID- 26895793 TI - MitoNEET-Parkin Effects in Pancreatic alpha- and beta-Cells, Cellular Survival, and Intrainsular Cross Talk. AB - Mitochondrial metabolism plays an integral role in glucose-stimulated insulin secretion (GSIS) in beta-cells. In addition, the diabetogenic role of glucagon released from alpha-cells plays a major role in the etiology of both type 1 and type 2 diabetes because unopposed hyperglucagonemia is a pertinent contributor to diabetic hyperglycemia. Titrating expression levels of the mitochondrial protein mitoNEET is a powerful approach to fine-tune mitochondrial capacity of cells. Mechanistically, beta-cell-specific mitoNEET induction causes hyperglycemia and glucose intolerance due to activation of a Parkin-dependent mitophagic pathway, leading to the formation of vacuoles and uniquely structured mitophagosomes. Induction of mitoNEET in alpha-cells leads to fasting-induced hypoglycemia and hypersecretion of insulin during GSIS. MitoNEET-challenged alpha-cells exert potent antiapoptotic effects on beta-cells and prevent cellular dysfunction associated with mitoNEET overexpression in beta-cells. These observations identify that reduced mitochondrial function in alpha-cells exerts potently protective effects on beta-cells, preserving beta-cell viability and mass. PMID- 26895795 TI - Body weight status and telomere length in U.S. middle-aged and older adults. AB - OBJECTIVE: Telomere length has been proposed as a biomarker of biological aging. This study examined the relationship between body weight status and telomere length in U.S. middle-aged and older adults. METHODS: Nationally representative data (N=2749) came from the Health and Retirement Study. Linear regressions were performed to examine the relationship between baseline body weight status reported in 1992 and telomere length measured in 2008 in the overall sample and by sex and racial/ethnic groups, adjusted for individual characteristics. RESULTS: Baseline overweight (25kg/m2<=body mass index [BMI]<30kg/m2) and obesity (BMI>=30kg/m2) status positively predicted telomere length 17 years later. Compared with their normal weight counterparts, telomere length ratio was on average 0.062 (95% confidence interval=0.016, 0.109) and 0.125 (0.048, 0.202) larger among overweight and obese adults, respectively. In comparison to women and racial/ethnic minorities, the estimated positive associations between overweight and obesity status and telomere length were more salient among men and non-Hispanic whites, respectively. CONCLUSIONS: The positive association between body weight status and telomere length found in this study was opposite to what existing biological model predicts, and could partially relate to the nonlinear relationship between body weight status and telomere length across age cohorts, and/or the lack of reliability of BMI as an indicator for adiposity in the older population. Large-scale longitudinal studies with baseline telomere length measures are warranted to replicate this study finding and explore the potential heterogeneous relationship between body weight status and telomere length. PMID- 26895797 TI - Identification and antimicrobial susceptibility testing of positive blood culture isolates from briefly incubated solid medium cultures. AB - INTRODUCTION: Mass spectrometry Matrix-Assisted Laser Desorption-Ionization Time of-Flight (MALDI-TOF) helps in the rapid identification of microorganisms causing blood stream infection. Rapid and reliable methods are required to decrease the turnaround time for reporting antimicrobial susceptibility results from blood culture isolates. METHODS: An evaluation was performed on the reliability of a method for antimicrobial susceptibility testing of positive blood culture isolates from briefly incubated solid medium cultures. RESULTS: The agreement between the evaluated and standard methods was 99.3%. The major and minor error rates were 0.4% and 0.3%, respectively, and no very major errors were observed. CONCLUSION: The inoculation of briefly incubated solid medium cultures into antimicrobial susceptibility testing panels is an easy and reliable technique, and helps to decrease the turnaround time for reporting antimicrobial susceptibility results of positive blood cultures. PMID- 26895796 TI - A Novel Biological Role of alpha-Mangostin in Modulating Inflammatory Response Through the Activation of SIRT-1 Signaling Pathway. AB - Several studies have shown that xanthones obtained from Garcinia Mangostana (GM) have remarkable biological activities. alpha-mangostin (alpha-MG) is the main constituent of the fruit hull of the GM. Several findings have suggested that SIRT-1, a nuclear histone deacetylase, could influence cellular function by the inhibition of NF-kB signaling. ROS can inhibit SIRT-1 activity by initiating oxidative modifications on its cysteine residues, and suppression of SIRT-1 enhances the NF-kappaB signaling resulting in inflammatory responses. The goals of the present study were to evaluate the quantity of alpha-MG in the methanolic extract of GM (Vithagroup Spa) and to investigate the activity of this xanthone in U937 cell line and in human monocytes from responsive to inflammatory insult analyzing the possible changes on the activation of SIRT-1 protein via NF-Kb. Cells were treated with the methanolic extract of GM and/or LPS. The chromatographic separation of alpha-MG was performed by an HPLC analysis. EX 527, a specific SIRT-1 inhibitor, was used to determine if SIRT-1/NfkB signaling pathway might be involved in alpha-MG action on cells. Our results show that alpha-MG inhibits p65 acetylation and down-regulates the pro-inflammatory gene products as COX-2, iNOS via SIRT-1 activation. Cells treated with EX 527 showed an up-regulation of NFkB acetylation and an over expression of inducible enzymes and their product of catalysis (NO and PGE2). These results suggest that alpha-MG may be useful for the development of alternative pharmacological strategies aimed at reducing the inflammatory process. J. Cell. Physiol. 231: 2439-2451, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26895798 TI - Lessons from the Italian NHS retrenchment policy. AB - In policymaking, implementation is often more critical than design. A variety of policy implementation frameworks can be used to explain implementation gaps and shifts. Each research stream suggests some solutions to prevent shortfalls. We have assessed two of these implementation strategies in the recent INHS (Italian National Health Service) retrenchment policies: (1) centralizing to rapidly cut expenditures, (2) effective management as an output- and not input-based system. The implementation of the INHS retrenchment policy has been very difficult though effective in a short period of time. A multi-level governance structure was put in place that assigned different but clear roles, powers and responsibilities to central and regional governments and public health care organizations. The entire policy was based on an exclusive input-based approach to introduce opacity in the system's prioritization processes. We most likely need to reconsider the identification of crucial implementation drivers in the public realm. PMID- 26895799 TI - [Preventive and curative value of yoga in cardiometabolic diseases]. AB - Yoga and other body-mind techniques enjoy an increasing popularity in many fields of health maintaining practices, in prevention of some illnesses and in curative medicine in spite of our incomplete knowledge about its applicability and effects. There are large differences among the various yoga-schools and the heterogeneity of indications etc. In this article a bucket of recent information is offered for the inquirers on the potential advantages of yoga (diet, mind exercises, asanas, pranayamas) for decreasing cardio-metabolic risk factors, stabilizing mental health, and its addictive use in curative medicine. Few adverse side-effects may occur only in the case of misapplication. Its advantages are low costs, availability for broad population, and very few contraindications. Disadvantages include differences in the ability of yoga instructors and in yoga practices. PMID- 26895800 TI - [Evaluation of the quality of performance of general practitioners. What is the problem with primary care quality indicators in Hungary?]. AB - The Hungarian primary care quality indicator system has been introduced in 2009, and has been continuously developed since then. The system offers extra financing for family physicians who are achieving the expected levels of indicators. There are currently 16 indicators for adult and mixed practices and 8 indicators are used in paediatric care. Authors analysed the influencing factors of the indicators other than those related to the performance of family physicians. Expectations and compliance of patients, quality of outpatient (ambulatory) care services, insufficient flow of information, inadequate primary care softwares which need to be updated could be considered as the most important factors. The level of financial motivations should also be significantly increased besides changes in the reporting system. It is recommended, that decision makers in health policy and financing have to declare clearly their expectations, and professional bodies should find the proper solution. These indicators could contribute properly to the improvement of the quality of primary care services in Hungary. PMID- 26895801 TI - [Treatment outcome of patients with essential thrombocythemia at our department in Hungary]. AB - INTRODUCTION: Essential thrombocythemia is a Philadelphia chromosome-negative chronic myeloproliferative neoplasia with a risk of bleeding and thromboembolic complications during the course of illness. Cytoreductive drugs, such as non selective hydroxyurea or interferon as first-line and specific, megakaryocyte thrombocyte reductive anagrelide chosen as second-line treatment in cases of adverse, intolerable effects of hydroxyurea can lower the incidence of bleeding/thrombotic episodes in patients with essential thrombocythemia. AIM: In this observational survey the effect of anagrelide was investigated in patients with essential thrombocythemia, who were first treated with hydroxyurea but failed to have clinicopathologic reponse (resistant) or were intolerant (adverse effects). METHOD: Between 2000 and 2014, 104 patients were diagnosed with essential thrombocythemia and treated first-line with hydroxyurea (weekly median dose of 7500 mg) in the haematologic outpatient department of the authors. Because of intolerance and/or resistance, hydroxyurea was changed to anagrelide (7.5 mg weekly median dose), the doses of hydroxyurea and anagrelide were adjusted to achieve clinicopathological response according to the updated criteria of the European LeukemiaNET. Effect of anagrelide as monotherapy (first- or second-line after hydroxyurea) or in combination with hydroxyurea was followed. Statistical analysis was performed using the Windows Statistical Package Program. RESULTS: Of the 104 patients with essential thrombocythemia (according to the updated WHO-ET classifications 58 patients JAK2V617F mutation positive, 46 patients negative, 15 patients calreticulin mutation negative, 6 patients MPL-1 mutation negative) 87 patients received hydroxyurea in first line, 4 patients interferon, and 13 patients acetylsalycilic acid only. Seven patients who proved to be intolerant and 22 patients who were resistant to hydroxyurea received anagrelide in second line (in 18 patients monotherapy and in 11 patients in combination with hydroxyurea), while other 5 rather young patients in first line therapy (34/104, 32.6%). In the anagrelide first line group 5 patients (100%), in the second line anagrelide monotherapy group 16 patients (88,8%), and in the combined hydroxyurea plus anagrelide group 9 patients (82.1%) achieved complete remission. The 10-year overall survival was 82.1%. In 2 patients treated with anagrelide major bleeding and in one patient myocardial infarction occurred, other serious adverse events due to anagrelide treatment were not detected. Three elder patients died from non-hematologic diseases, but leukaemic transformation was not observed. CONCLUSIONS: First or second line anagrelide therapy, combined with hydroxyurea if necessary, was able to reduce the platelet-count and the rate of complications, and to control the course of essential thrombocythemia with tolerable adverse effects. PMID- 26895802 TI - [Motivations for foreign employment and carrier change among Hungarian physiotherapists]. AB - INTRODUCTION: An increasing motivation can be experienced among professional workers within the Hungarian healthcare system towards foreign employment or career change. AIM: The aim of the authors was to assess Hungarian physiotherapists' migration and career changing behaviour and to understand the underlying factors. METHOD: A national survey in Hungary from April to August, 2014 was performed. Only physiotherapists who practice in Hungary were included (n = 215). RESULTS: The results suggest that age (p<0.05) and the rate of financial appreciation experienced in the workplace (p<0.01) significantly affect the appearance of migratory thoughts. Those physiotherapists who do not feel themselves financially appreciated, are 55 times more likely to search for employment outside the country's borders [OR = 55.28 CI (95%) = 18.85 to 161.12]. The most common causes for that are unfavourable financial (p<0.01) and moral recognition (p<0.01). CONCLUSIONS: In order to prevent our already highly qualified colleagues from leaving the country or from considering to leave the profession we should concentrate on increasing the financial and moral appreciation of the profession within the Hungarian healthcare system. PMID- 26895804 TI - [Mirroring Semmelweis'es observations in the Hungarian medical literature]. PMID- 26895803 TI - [The Great Imitator. Case report]. AB - Authors present two patients suffering from renal tuberculosis, which caused differential diagnostic problems. The first patient was examined because of fever and left flank pain. Computed tomography revealed renal shrinkage on the left side. Retrograde pyelography demonstrated ureteric stricture and dilated calices. Urine culture showed Mycobacterium tuberculosis. Two months after initiation of the antituberculotic therapy nephrectomy was performed. The second patient was referred to the department because of fever after unsuccessful antibiotic treatment. Ultrasound examination showed a staghorn stone, dilated renal pelvis and perirenal abscess on the left side. Double J catheter insertion and percutaneous puncture of the abscess were performed. Culture of the pus aspirated proved Proteus morganii. Fever and complaints of the patient relieved after antibiotic treatment. Two months later double J catheter was changed because of persistent pyelonephritis. One week later the patient returned to the hospital with fever, which could not be reduced with intravenous antibiotics. Computed tomography showed purulent fluid in the left kidney, and nephrectomy was performed. Histology revealed renal tuberculosis. The authors summarize the diagnosis and treatment of renal tuberculosis on the basis of these two cases. PMID- 26895805 TI - Child and adolescent sports participant issues. PMID- 26895806 TI - Visceral leishmaniasis: a forgotten epidemic. AB - Visceral leishmaniasis (VL or kala-azar) is most endemic in Asia and Africa and commonly affects young children. It is usually caused by Leishmania donovani or Leishmania infantum that are transmitted by Phlebotomine sand flies. Transmission may be anthroponotic or zoonotic or both, depending on the endemic area. Clinical features include fever, hepatosplenomegaly, weight loss and pancytopenia. Younger age, malnutrition and immunosuppression (HIV infection, use of immunosuppressive drugs) are risk factors. Many infections remain asymptomatic. Diagnosis is made by demonstration of the Leishmania parasite in aspirates of lymph node, bone marrow or spleen. Serological tests such as rK39 strip test are widely used but the sensitivity varies. qPCR is useful to detect low numbers of parasites and to monitor treatment. Treatment is with AmBisome monotherapy in most areas but with drug combinations elsewhere. HIV co-infected patients are most difficult to treat and often relapse. Control efforts focus on case finding, availability of diagnostic tools, reservoir control and protection from sand flies (insecticides, bed nets). There is no human vaccine. PMID- 26895807 TI - Utilization of free medication samples in the United States in a nationally representative sample: 2009-2013. AB - BACKGROUND: Manufacturers provide free sample medications as a means to increase use of branded medications. Sample use varies year-to-year as branded product patents expire and new products come to market. OBJECTIVE: This study sought to describe the use of sample medications during 2009-2013 and assess individual characteristics associated with sample use. METHODS: Data from the 2009-2013 U.S. Medical Expenditure Panel Survey (MEPS) were used. MEPS asks participants whether they received each medication they are taking as a sample. The top 10 medications and medication classes used each year by volume were identified as well as the proportion of people who used at least one sample medication. The proportion of new initiators of medications were also classified as the percent who received a sample for the specific medication. Logistic regression was used to assess individual demographics, insurance, and medication characteristics associated with use. RESULTS: Prevalence of sample use ranged from 9.3% in 2009 to 6.2% in 2013. The most widely used sample medications included statins during 2009-2011, which changed to inhaled beta-agonists in 2012-2013, as atorvastatin became available as a generic. The overall volume of the top 10 free sample medications decreased by one-third over this study period. In 2013, 12.6% of new insulin analog users and 11.0% of new oral contraceptive users receive these medications through samples. Regression analysis showed that U.S. Medicaid- and Medicare insured persons were less likely to use samples compared to those with private insurance. CONCLUSIONS: Sample medication use has decreased as generic medications are becoming more used in the U.S. PMID- 26895808 TI - Fat embolism syndrome: State-of-the-art review focused on pulmonary imaging findings. AB - BACKGROUND: Fat embolism syndrome (FES) is a rare but potentially fatal complication of trauma or orthopedic surgery, which presents predominantly with pulmonary symptoms. Modern intensive care has improved the mortality rates, however diagnosis remains difficult, relying predominantly on a combination of a classic triad of symptoms and non-specific, but characteristic radiological features. The aim of this review is to describe the main clinical and imaging aspects of FES, ranging from pathophysiology to treatment with emphasis on pulmonary involvement. METHODS: We reviewed the currently published literature on the main characteristics of FES. RESULTS: In a hypoxic patient with recent trauma or orthopedic surgery, the presence of diffuse, well-demarcated ground glass opacities or ill-defined centrilobular nodules on computed tomography (CT) of the chest are suggestive of FES. CONCLUSIONS: Combination of the classic clinical syndrome in the appropriate clinical setting, together with the characteristic imaging findings on chest CT, can help to achieve the correct diagnosis. Management remains predominantly supportive care, and the benefit of medical therapies such as corticosteroids and heparin remains unclear. PMID- 26895809 TI - Current thinking and new paradigm for COPD. AB - During the 2015 European Respiratory Society Congress, a symposium was held on 'Current thinking and new paradigm for COPD'. Through a combination of plenary lectures and interactive panel discussions, experts discussed the recent evidence for chronic obstructive pulmonary disease (COPD) treatment and how this evidence can be applied in clinical practice. PMID- 26895810 TI - Genomic Characterization of Renal Cell Carcinoma with Sarcomatoid Dedifferentiation Pinpoints Recurrent Genomic Alterations. AB - BACKGROUND: The genomic features underpinning renal cell carcinoma with sarcomatoid dedifferentiation (sRCC) are not well understood, and at present, there are no specific or effective therapies for sRCC. OBJECTIVE: To identify genomic alterations in patients with sRCC. DESIGN, SETTING, AND PARTICIPANTS: We conducted genomic profiling on paired epithelial and sarcomatoid areas of three sRCC cases. Genomic profiling was performed on another 23 sRCC patients harboring diverse epithelial components (total of 26 cases). Genomic profiling was conducted using a hybrid capture DNA next-generation sequencing assay of 236 cancer-related genes plus 19 genes frequently rearranged in cancer. Results were compared with 56 similarly sequenced cases of clear cell RCC (ccRCC) devoid of a sarcomatoid component, and with clear cell, papillary, and chromophobe renal cell carcinoma datasets from The Cancer Genome Atlas. Four additional ccRCC cases underwent whole exome sequencing. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Genomic alterations in patients with sRCC and ccRCC were described, and their frequencies were compared using the Fisher exact test. RESULTS AND LIMITATIONS: Two of three patients with sRCC who underwent genomic profiling of both their epithelial and sarcomatoid components demonstrated identical mutational profiles, and a third case demonstrated commonly disrupted genes. Of the 26 sRCCs, TP53 (42.3%), VHL (34.6%), CDKN2A (26.9%), and NF2 (19.2%) were the most frequently altered genes. NF2 mutations were mutually exclusive with TP53 but not with VHL mutations. Limitations include the small sample size. CONCLUSIONS: We found that sRCC contains different driver mutations than ccRCC. The epithelial and sarcomatoid components of sRCC largely contain the same genomic features. On the basis of harboring either TP53 or NF2 mutations, sRCC can be divided into two groups. These findings may have implications for understanding the oncogenesis of sarcomatoid renal tumors and for defining systemic treatment options. PATIENT SUMMARY: Next-generation sequencing of tumors from patients with sarcomatoid kidney cancer reveals mutations that differ from those in nonsarcomatoid patients. These findings have implications in understanding the pathobiology of sarcomatoid kidney cancer and indicate the need for a different treatment approach in these patients. PMID- 26895812 TI - Erratum to: Detection of bacteria in middle ear effusions based on the presence of allergy: does allergy augment bacterial infection in the middle ear? PMID- 26895811 TI - Factors associated with psychiatric symptoms and psychiatric disorders in ethnic minority youth. AB - While ethnic diversity is increasing in many countries, ethnic minority youth is less likely to be reached, effectively treated and retained by youth mental health care compared to majority youth. Improving understanding of factors associated with mental health problems within socially disadvantaged ethnic minority youth is important to tailor current preventive and treatment interventions to the needs of these youth. The aim of this study was to explore factors at child, family, school, peer, neighbourhood and ethnic minority group level associated with mental health problems in Moroccan-Dutch youth (n = 152, mean age 13.6 +/- 1.9 years). Self-reported and teacher-reported questionnaire data on psychiatric symptoms and self-report interview data on psychiatric disorders were used to divide children into three levels of mental health problems: no symptoms, only psychiatric symptoms and psychiatric disorders. Psychiatric symptoms and/or disorders were associated with more psychopathic traits, a higher number of experienced trauma and children in the family, and more conflicts with parents, affiliation with delinquent peers, perceived discrimination and cultural mistrust. Psychiatric symptoms and/or disorders were also associated with less self-esteem, parental monitoring, affiliation with religion and orientation to Dutch or Moroccan culture, and a weaker ethnic identity. For youth growing up in a disadvantaged ethnic minority position, the most important factors were found at family (parent-child relationship and parenting practices) and ethnic minority group level (marginalization, discrimination and cultural mistrust). Preventive and treatment interventions for socially disadvantaged ethnic minority youth should be aimed at dealing with social disadvantage and discrimination, improving the parent-child relationship and parenting practices, and developing a positive (cultural) identity. PMID- 26895813 TI - Nutritional follow-up of patients after obesity surgery: best practice. AB - Obesity surgery is an appropriate treatment option for patients with severe and complex obesity and helps in the improvement of comorbidities. In the first 2 years following surgery, follow-up is provided by the obesity surgery centre. Ongoing care is then usually returned to the general practitioner. Patients need access to ongoing support and monitoring otherwise may be at risk of developing nutritional deficiencies such as anaemia or protein malnutrition. The British Obesity and Metabolic Surgery Society have developed guidelines on nutritional monitoring and nutritional supplements to support both bariatric centres and general practitioners. The Royal College of General Practitioners and BOMSS have worked collaboratively to develop Ten Top Tips for the management of obesity surgery patients to aid with the long-term management in primary care. Women, planning to get pregnant, need access to preconception advice and additional monitoring during pregnancy. It is essential that long-term data are collected and inputted into the National Bariatric Surgery Register. Obesity surgery improves comorbidities; however, patients must have access to long-term nutritional monitoring. PMID- 26895814 TI - Response to Demetter et al.: review of the quality of total mesorectal excision does not improve the prediction of outcome. PMID- 26895815 TI - PD-L1 expression in cancer patients receiving anti PD-1/PD-L1 antibodies: A systematic review and meta-analysis. AB - BACKGROUND: Despite the success of immunotherapy directed at inhibiting of programmed death-1 (PD-1)/PD-ligand (L)1 signaling, it is not established whether PD-L1 expression correlates with the clinical response and outcome in different tumors. The present meta-analysis investigates whether the PD-L1 status, detected by immunohistochemistry, is associated with clinical response and mortality in patients treated with anti-PD-1/PD-L1 therapy. METHODS: A systematic literature search and quantitative analysis were planned, conducted and reported following CONSORT and QUORUM checklists, up to December 2015, to identify clinical trials with information on cancer outcome by PD-L1 immunohistochemical expression in tumor tissues. We used random effects models to estimate Summary Objective Response Rates (SORRs) and Summary Odd Ratio (SOR) for the comparison of PD-L1 positive and negative patients. RESULTS: We summarized 20 trials carried out in metastatic melanoma (MM), non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC) patients receiving anti-PD-1/PD-L1 antibodies (4230 MM, 1417 NSCLC and 312 RCC patients). Positive PD-L1 MM patients showed a significant decrease (53%) in the risk of mortality vs. negative cases with no heterogeneity. Furthermore, SORRs were 45% and 27% in PD-L1 positive and negative patients, respectively, and SOR indicates a significant difference in term of responses: 2.14 (95% CI: 1.65, 2.77), with low between-study heterogeneity (I(2)=35%). Furthermore, results from randomized clinical trials on MM showed that PD-L1 expression is significantly associated with greater clinical response rates to anti-PD1 treatments (SOR 1.89; 95%CI: 1.35, 2.64) but not to other treatments (SOR 0.96; 95%CI: 0.5, 1.87). In non-squamous NSCLC SORRs were 29% and 11% in PD L1 positive and negative patients, respectively, and SOR indicates a significant difference between responses: 3.78 (1.54, 9.24), with no between-study heterogeneity. Squamous NSCLC and RCC did not show any significant difference in response according to the PD-L1 status. CONCLUSION: PD-L1 expression is significantly associated with mortality and clinical response to anti-PD-1/PD-L1 antibodies in MM patients and with clinical response in patients with non squamous NSCLC. PMID- 26895816 TI - Interceed and Estrogen Reduce Uterine Adhesions and Fibrosis and Improve Endometrial Receptivity in a Rabbit Model of Intrauterine Adhesions. AB - Intrauterine adhesions (IUA) remain a major cause of infertility. Interceed, a regenerated cellulose adhesion barrier, is used to prevent adhesions in abdominal cavity. This study aimed to determine whether Interceed could reduce adhesions and tissue fibrosis and improve endometrial receptivity (ER) in rabbit. Rabbits were randomized into 6 groups: sham operation, Interceed control, IUA model, Interceed therapy, estrogen therapy, and combination therapy. Four rabbits per group were euthanized to evaluate adhesion severity on the day before intervention and day 7, 14, and 28 after intervention. Number of endometrial glands and degree of endometrial fibrosis acted as markers for adhesion severity. Pseudopregnancy was induced in the remainder, and 8 rabbits per group were killed for assessing ER on days 6, 7, and 8 of pseudopregnancy by alphanubeta3 integrin and pinopode. We found that Interceed or estrogen therapy led to significant improvement in the adhesion severity on day 28 after intervention, respectively, compared to IUA model group (all P < .05). However, after combination therapy, such improvement achieved comparable to sham operation group as early as day 14 after intervention (glands, P = .711, fibrosis, P = .154). Among the IUA models treated, ER was highest after combination therapy on day 7 of pseudopregnancy, similar to sham operation group (integrin, P = .352, pinopode, P = .154). In conclusion, Interceed and estrogen reduce adhesions and tissue fibrosis and improve ER in a rabbit model and may be novel therapeutic approaches for infertility resulting from IUA. PMID- 26895817 TI - The Hidden History of a Famous Drug: Tracing the Medical and Public Acculturation of Peruvian Bark in Early Modern Western Europe (c. 1650-1720). AB - The history of the introduction of exotic therapeutic drugs in early modern Europe is usually rife with legend and obscurity and Peruvian bark is a case in point. The famous antimalarial drug entered the European medical market around 1640, yet it took decades before the bark was firmly established in pharmaceutical practice. This article argues that the history of Peruvian bark can only be understood as the interplay of its trajectories in science, commerce, and society. Modern research has mostly focused on the first of these, largely due to the abundance of medico-historical data. While appreciating these findings, this article proposes to integrate the medical trajectory in a richer narrative, by drawing particular attention to the acculturation of the bark in commerce and society. Although the evidence we have for these two trajectories is still sketchy and disproportionate, it can nevertheless help us to make sense of sources that have not yet been an obvious focus of research. Starting from an apparently isolated occurrence of the drug in a letter, this article focuses on Paris as the location where medical and public appreciation of the bark took shape, by exploring several contexts of knowledge circulation and medical practice there. These contexts provide a new window on the early circulation of knowledge of the bark, at a time when its eventual acceptance was by no means certain. PMID- 26895818 TI - Early Postoperative Outcomes After Total Joint Arthroplasty in Patients With Multiple Myeloma. AB - BACKGROUND: Multiple myeloma is the most common primary bone malignancy and is increasingly becoming a chronic condition, but little is known about its impact in the perioperative arthroplasty setting. We sought to determine whether patients with multiple myeloma undergoing elective total joint arthroplasty would be at increased risk for in-hospital complications and death, prolonged length of stay, and nonroutine discharge. METHODS: Using discharge records from the Nationwide Inpatient Sample (2002-2011), we identified 6,054,344 patients undergoing elective primary total joint arthroplasty, of whom 2381 (0.039%) with multiple myeloma. Comparisons of perioperative outcomes were performed by multivariable logistic regression modeling. RESULTS: Patients with multiple myeloma were more likely to suffer several postoperative complications, including thromboembolic events (odds ratio [OR]: 2.97, 95% CI: 2.32-3.81), surgical site infection (OR: 2.82, 95% CI: 1.59-5.01), acute renal failure (OR: 1.93, 95% CI: 1.59-2.37), and induced mental disorder (OR: 1.57, 95% CI: 1.21-2.04). A diagnosis of multiple myeloma was also associated with higher risk for blood transfusion (OR: 2.14, 95% CI: 1.97-2.33), prolonged hospital stay (OR: 2.04, 95% CI: 1.86-2.23), and nonroutine discharge (OR: 1.33, 95% CI: 1.21-1.45) but was not associated with greater in-hospital mortality. CONCLUSION: Patients with multiple myeloma are at increased risk for early postoperative complications (especially surgical site infection and thromboembolic events) and resource utilization after elective joint arthroplasty. Greater awareness of multiple myeloma and its health consequences may contribute to improvements in the perioperative management of total joint arthroplasty patients. PMID- 26895819 TI - Medicare's Hospital-Acquired Conditions Policy: A Problem of Nonpayment After Total Joint Arthroplasty. AB - BACKGROUND: Total joint arthroplasty (TJA) utilization continues to increase, and optimizing efficiency while reducing complications is critical to provide a sustainable product. Recent policy has defined several hospital-acquired conditions (HACs) that are the target of reducing complications with significant financial implications. The present study defines the incidence of HACs after TJA as well as patient and hospital factors associated with HACs. METHODS: The National Inpatient Sample (NIS) was used to identify all patients from 2009 to 2011 undergoing elective total hip or knee arthroplasty. Patient demographics, comorbidities, and hospital characteristics were obtained from the database, and HACs defined according to established International Classification of Diseases, Ninth Revision, Clinical Modification criteria. The incidence of HACs after TJA was calculated, as were demographic factors and preadmission comorbidities associated with HACs using bivariate and multivariable analysis. RESULTS: The overall incidence of HACs after TJA was 1.3%. Several patient and hospital factors, including increased age, female gender, black race, medium hospital bed size, year of surgery, and Charlson Comorbidity Index >=1, independently predicted development of a HAC. When evaluating the financial impact of the development of a HAC after TJA, more than 200 million dollars in hospital costs would be lost during the inclusive years of this study, equating to nearly 70 million dollars annually. CONCLUSION: The incidence of HACs after TJA is 1.3%. Many of the patient factors associated with HACs are nonmodifiable, and risk adjustment should be considered to provide a sustainable product to a diverse patient population. PMID- 26895820 TI - Hyaluronic Acid Injections in Medicare Knee Osteoarthritis Patients Are Associated With Longer Time to Knee Arthroplasty. AB - BACKGROUND: Few nonoperative treatment options for knee osteoarthritis (OA) are available, but there is ongoing debate about the effectiveness of intra-articular (IA) hyaluronic acid (HA) injections. We investigated whether the formulation of IA HA, or its combined use with IA corticosteroid (CS), may be contributing to some of the reported variation in clinical outcomes. METHODS: The 5% Part B Medicare data (2005-2012) were used to identify knee OA patients who underwent knee arthroplasty (KA). The time from diagnosis of OA to KA was compared between patients with (HA) and without (no HA) IA HA use, using quantile regression with propensity score adjustment. These were further stratified by type of IA HA. Patient factors associated with time to KA were also assessed using Cox regression. RESULTS: The "HA" cohort was associated with a longer time to KA of 8.7 months (95% confidence interval: 8.3-9.1 months; P < .001) compared with the "no HA" cohort, with extended time to KA in the bioengineered Euflexxa IA HA cohort. Patient factors associated with longer time to KA included women, younger patients, minority patients, patients with fewer comorbidities, and IA CS injection use. Patients with both IA HA and IA CS had an additional 6.3 months (95% confidence interval: 5.5-7.0 months; P < .001) to KA over those with only IA HA. CONCLUSION: In a large cohort of elderly patients undergoing KA, there was a significant longer time from diagnosis of OA to KA in those receiving IA HA. It is unclear if the extended time may lead to less KA utilization. PMID- 26895821 TI - Is Ultrasound As Useful As Metal Artifact Reduction Sequence Magnetic Resonance Imaging in Longitudinal Surveillance of Metal-on-Metal Hip Arthroplasty Patients? AB - BACKGROUND: Current guidelines recommend longitudinal monitoring of at-risk metal on-metal (MoM) arthroplasty patients with cross-sectional imaging such as metal artifact reduction sequence (MARS) magnetic resonance imaging (MRI) or ultrasound. During follow-up evaluations, the clinical focus is on the relative interval changes in symptoms, radiographs, laboratory tests, and cross-sectional imaging modalities. Although MRI has the capacity for the detection of adverse local soft tissue reactions (ALTRs), the potential disadvantages of MARS MRI include the obscuration of periprosthetic tissues by metal artifacts and the cost. The aim of this study was to evaluate the diagnostic accuracy of ultrasound in comparison with MARS MRI in detecting ALTR in MoM patients during consecutive follow-up. METHODS: Thirty-five MoM patients (42 hips) were recruited prospectively to evaluate the sensitivity and specificity of the ultrasound for detecting ALTR in relation to MARS MRI during 2 longitudinal follow-up scans. The agreement between ultrasound and MARS MRI in ALTR grade, size, and size change was calculated. RESULTS: At the initial evaluation and at the subsequent follow up, ultrasound had a sensitivity of 81% and 86% and a specificity of 92% and 88%, respectively. At the follow-up evaluations, ultrasound was able to detect the "change" in the lesions size with -0.3 cm(2) average bias from the MARS MRI with higher agreement (k = 0.85) with MARS MRI compared to the initial evaluation in detecting any "change" in ALTR size or grade. CONCLUSION: Ultrasound detected the interval change in the ALTR size and grade with higher accuracy and higher agreement with MARS MRI compared with the initial evaluation, suggesting ultrasound is a valid and useful. PMID- 26895822 TI - Early Outcomes of Revision Surgery for Taper Corrosion of Dual Taper Total Hip Arthroplasty in 187 Patients. AB - BACKGROUND: Modular dual taper femoral neck designs have been associated with taper corrosion requiring revision surgery. However, outcomes after revision dual taper total hip arthroplasty in patients with symptomatic adverse local tissue reaction due to taper corrosion remain largely unknown. METHODS: A total of 198 revision surgeries in 187 patients with dual taper femoral stem total hip arthroplasty with minimum 12-month follow-up were evaluated. RESULTS: At mean follow-up of 18 months, at least 1 complication had occurred in 39 patients (20%) of 198 revisions. Single episode of dislocation, treated with close reduction, occurred in 16, whereas 2 patients required rerevision due to multiple dislocations. Infection requiring rerevision occurred in 3 patients. Adverse local tissue reaction recurrence requiring reoperation occurred in 6 patients. Implant survivorship for revision for any cause was 86% at 30 months. The reoperation rate of revised dual taper was 8% (16 out of 198 hips). The median serum levels of cobalt, chromium, and cobalt/chromium ratio decreased (P < .01) from 5.3 MUg/L (range: 2.3-48.5 MUg/L), 2.6 MUg/L (range: 0.2-64 MUg/L), and 4.7 (range: 2.1-35) prerevision to 1.4 MUg/L (range: 0.2-8.8 MUg/L), 0.7 MUg/L (range: 0.1-3.9 MUg/L), and 2.2 (range: 0.4-8.8) postrevision, respectively. CONCLUSION: This pilot study demonstrates that intraoperative tissue necrosis was associated with a high rate of early complications (20%) and revisions (8%), suggesting the importance of a systematic evaluation of these patients including metal ion levels and metal artifact reduction sequence magnetic resonance imaging in optimizing revision outcome, as early diagnosis will facilitate the initiation of appropriate treatment before significant adverse tissue necrosis. PMID- 26895823 TI - Cemented vs Cementless Total Knee Arthroplasty in Morbidly Obese Patients. AB - BACKGROUND: Primary total knee arthroplasty (TKA) in morbidly obese patients has been associated with greater postoperative complications. Cementless TKA has the potential for biologic fixation which may provide more durable long-term stability. METHODS: This was a multicenter review of 298 TKAs in 292 morbidly obese patients (body mass index, >40) undergoing TKA, with 154 TKAs (149 patients) in the cemented and 144 TKAs (143 patients) in the cementless group. RESULTS: There were significantly more revisions in the cemented group (n = 20) than in the cementless group (n = 1; 13.0% vs 0.7%). There was a significantly higher incidence of aseptic loosening in the cemented cohort vs the cementless cohort (9 vs 0 TKAs). All revisions in the cementless cohort were due to infection (0.7%). CONCLUSION: Cementless fixation may be an alternative in the morbidly obese patient undergoing primary TKA. PMID- 26895824 TI - Alcohol consumption among university students in Ireland and the United Kingdom from 2002 to 2014: a systematic review. AB - BACKGROUND: Alcohol is a leading cause of global suffering. Europe reports the uppermost volume of alcohol consumption in the world, with Ireland and the United Kingdom reporting the highest levels of binge drinking and drunkenness. Levels of consumption are elevated among university students. Thus, this literature review aims to summarise the current research on alcohol consumption among university students in the Republic of Ireland and the United Kingdom. METHODS: MEDLINE, CINAHL, EMBASE and PsychInfo were systematically searched for literature from January 2002 until December 2014. Each database was searched using the following search pillars: alcohol, university student, Ireland or the United Kingdom and prevalence studies. RESULTS: Two thousand one hundred twenty eight articles were retrieved from electronic database searching. These were title searched for relevance. 113 full texts were retrieved and assessed for eligibility. Of these, 29 articles were deemed to meet inclusion criteria for the review. Almost two thirds of students reported a hazardous alcohol consumption score on the AUDIT scale. Over 20% reported alcohol problems over their lifetime using CAGE while over 20% exceed sensible limits each week. Noteworthy is the narrowing of the gender gap throughout the past decade. CONCLUSION: This is the first review to investigate consumption patterns of university students in Ireland and the United Kingdom. A range of sampling strategies and screening tools are employed in alcohol research which preclude comparability. The current review provides an overview of consumption patterns to guide policy development. PMID- 26895826 TI - From protocol to published report: a study of consistency in the reporting of academic drug trials. AB - BACKGROUND: Unacknowledged inconsistencies in the reporting of clinical trials undermine the validity of the results of the trials. Little is known about inconsistency in the reporting of academic clinical drug trials. Therefore, we investigated the prevalence of consistency between protocols and published reports of academic clinical drug trials. METHODS: A comparison was made between study protocols and their corresponding published reports. We assessed the overall consistency, which was defined as the absence of discrepancy regarding study type (categorized as either exploratory or confirmatory), primary objective, primary endpoint, and--for confirmatory trials only--hypothesis and sample size calculation. We used logistic regression, chi(2), and Fisher's exact test. RESULTS: A total of 282 applications of academic clinical drug trials were submitted to the Danish Health and Medicines Authority in 1999, 2001, and 2003, 95 of which fulfilled the eligibility criteria and had at least one corresponding published report reporting data on trial subjects. Overall consistency was observed in 39% of the trials (95% CI: 29 to 49%). Randomized controlled trials (RCTs) constituted 72% (95% CI: 63 to 81%) of the sample, and 87% (95% CI: 80 to 94%) of the trials were hospital based. CONCLUSIONS: Overall consistency between protocols and their corresponding published reports was low. Motivators for the inconsistencies are unknown but do not seem restricted to economic incentives. PMID- 26895829 TI - Evaluation of innovative stationary phase ligand chemistries and analytical conditions for the analysis of basic drugs by supercritical fluid chromatography. AB - Similar to reversed phase liquid chromatography, basic compounds can be highly challenging to analyze by supercritical fluid chromatography (SFC), as they tend to exhibit poor peak shape, especially those with high pKa values. In this study, three new stationary phase ligand chemistries available in sub -2 MUm particle sizes, namely 2-picolylamine (2-PIC), 1-aminoanthracene (1-AA) and diethylamine (DEA), were tested in SFC conditions for the analysis of basic drugs. Due to the basic properties of these ligands, it is expected that the repulsive forces may improve peak shape of basic substances, similarly to the widely used 2 ethypyridine (2-EP) phase. However, among the 38 tested basic drugs, less of 10% displayed Gaussian peaks (asymmetry between 0.8 and 1.4) using pure CO2/methanol on these phases. The addition of 10mM ammonium formate as mobile phase additive, drastically improved peak shapes and increased this proportion to 67% on 2-PIC. Introducing the additive in the injection solvent rather than in the organic modifier, gave acceptable results for 2-PIC only, with 31% of Gaussian peaks with an average asymmetry of 1.89 for the 38 selected basic drugs. These columns were also compared to hybrid silica (BEH), DIOL and 2-EP stationary phases, commonly employed in SFC. These phases commonly exhibit alternative retention and selectivity. In the end, the two most interesting ligands used as complementary columns were 2-PIC and BEH, as they provided suitable peak shapes for the basic drugs and almost orthogonal selectivities. PMID- 26895825 TI - Characterization of acetic acid-detoxifying Escherichia coli evolved under phosphate starvation conditions. AB - BACKGROUND: During prolonged incubation of Escherichia coli K-12 in batch culture under aerobic, phosphate (Pi) starvation conditions, excess glucose is converted into acetic acid, which may trigger cell death. Following serial cultures, we isolated five evolved strains in two populations that survived prolonged incubation. METHODS: We sequenced the genomes of the ancestral and evolved strains, and determined the effects of the genetic changes, tested alone and in combination, on characteristic phenotypes in pure and in mixed cultures. RESULTS: Evolved strains used two main strategies: (1) the constitutive expression of the Trk- and Kdp-dependent K(+) transport systems, and (2) the inactivation of the ArcA global regulator. Both processes helped to maintain a residual activity of the tricarboxylic acid cycle, which decreased the production of acetic acid and eventually allowed its re-consumption. Evolved strains acquired a few additional genetic changes besides the trkH, kdpD and arcA mutations, which might increase the scavenging of organophosphates (phnE (+), lapB, and rseP) and the resistance to oxidative (rsxC) and acetic acid stresses (e14(-)/icd (+)). CONCLUSIONS: Evolved strains rapidly acquired mutations (phnE (+) lapB rpoS trkH and phnE (+) rseP kdpD) that were globally beneficial to growth on glucose and organophosphates, but detrimental to long-term viability. The spread of these mutant strains might give the ancestral strain time to accumulate up to five genetic changes (phnE (+) arcA rsxC crfC e14(-)/icd (+)), which allowed growth on glucose and organophosphates, and provided a long-term survival. The latter strain, which expressed several mechanisms of protection against endogenous and exogenous stresses, might provide a platform for producing toxic recombinant proteins and chemicals during prolonged incubation under aerobic, Pi starvation conditions. PMID- 26895827 TI - Clinical implications of human papilloma virus and other biologic markers in nasopharyngeal cancer. PMID- 26895830 TI - Separation and isolation of saturated and unsaturated 5-n-alk(en)ylresorcinols from rye bran. AB - Alkylresorcinols (AR) are a class of phenolic lipids which are found in a number of plants and microorganisms and which are associated with various biological activities. In view of the very limited availability of reference compounds, we developed a process for the isolation of AR from rye bran. For this purpose, a crude extract was subjected to deep bed filtration at -80 degrees C, whereby the crystallized saturated AR were separated from the unsaturated homologues. Highly purified, individual compounds were subsequently isolated by semi-preparative HPLC. In contrast to previously published approaches, the method reported here is relatively easy to perform and allows the recovery of saturated and unsaturated AR of high purity. Furthermore, it is superior to argentation chromatography because it does not necessitate the removal of silver ions for subsequent bioassays. PMID- 26895831 TI - Revascularization of the femoral head by anastomosis of superior retinacular vessels for the treatment of femoral neck fracture: A case report. AB - The purpose of this report is to present a method of revascularization of the femoral head for the treatment of femoral neck fracture in a young adult. The patient is a 22-year-old male with the femoral neck fracture of Garden type III. We performed an open reduction with internal fixation of the fracture and repaired the superior retinacular vessels using microsurgical techniques to achieve revascularization to the femoral head. A desensitized-digital subtraction angiography examination showed that the blood supply from the superior retinacular artery to the femoral head was re-established three months after surgery. The X-ray showed that the femoral head had a normal shape without any necrotic lesions or sclerotic changes at four months follow-up and the bone achieved good union without redisplacement of the fracture site. This case showed that revascularization of the femoral head by microsurgery could be feasible in treatment of certain type of femoral neck fracture. (c) 2016 Wiley Periodicals, Inc. Microsurgery 36:426-429, 2016. PMID- 26895832 TI - Clinical Isolates of Pseudomonas aeruginosa from Chronically Infected Cystic Fibrosis Patients Fail To Activate the Inflammasome during Both Stable Infection and Pulmonary Exacerbation. AB - Immune recognition of pathogen-associated ligands leads to assembly and activation of inflammasomes, resulting in the secretion of inflammatory cytokines IL-1beta and IL-18 and an inflammatory cell death called pyroptosis. Inflammasomes are important for protection against many pathogens, but their role during chronic infectious disease is poorly understood. Pseudomonas aeruginosa is an opportunistic pathogen that persists in the lungs of cystic fibrosis (CF) patients and may be responsible for the repeated episodes of pulmonary exacerbation characteristic of CF. P. aeruginosa is capable of inducing potent inflammasome activation during acute infection. We hypothesized that to persist within the host during chronic infection, P. aeruginosa must evade inflammasome activation, and pulmonary exacerbations may be the result of restoration of inflammasome activation. We therefore isolated P. aeruginosa from chronically infected CF patients during stable infection and exacerbation and evaluated the impact of these isolates on inflammasome activation in macrophages and neutrophils. P. aeruginosa isolates from CF patients failed to induce inflammasome activation, as measured by the secretion of IL-1beta and IL-18 and by pyroptotic cell death, during both stable infection and exacerbation. Inflammasome evasion likely was due to reduced expression of inflammasome ligands and reduced motility and was not observed in environmental isolates or isolates from acute, non-CF infection. These results reveal a novel mechanism of pathogen adaptation by P. aeruginosa to avoid detection by inflammasomes in CF patients and indicate that P. aeruginosa-activated inflammasomes are not involved in CF pulmonary exacerbations. PMID- 26895833 TI - MLN4924, a First-in-Class NEDD8-Activating Enzyme Inhibitor, Attenuates IFN-beta Production. AB - Neddylation is a posttranslational protein modification that conjugates ubiquitin like protein neural precursor cell-expressed developmentally downregulated protein 8 (NEDD8) to target proteins and regulates diverse cellular processes. MLN4924, a novel NEDD8 activating enzyme inhibitor, which has emerged as a promising anticancer drug, has a multifaceted function by inhibiting the process of neddylation. However, the potential roles of MLN4924 and neddylation in IFN beta production remain unknown. In this study, we show that MLN4924 inhibits TLR3/4- and retinoic acid-inducible gene-I-induced IFN-beta expression in different cells, whereas NEDD8 knockdown had no effects on IFN-beta expression. The ability of the MLN4924 to inhibit IFN-beta production was confirmed in vivo, as mice treated with MLN4924 exhibited decreased levels of IFN-beta upon LPS or polyinosinic-polycytidylic acid stimulation. Furthermore, we show that MLN4924 inhibits IFN regulatory factor 3 (IRF3) transcriptional activation and prevents IRF3 binding to IFN-beta promoter. Our findings suggest that MLN4924 inhibits TLR3/4- and retinoic acid-inducible gene-I-induced IFN-beta expression by preventing IRF3 binding to the IFN-beta promoter, with a neddylation-independent manner. Therefore, our results provide new insight into the mechanism of MLN4924 and may have significant implications for the treatment of MLN4924. PMID- 26895834 TI - Healthy HLA-DQ2.5+ Subjects Lack Regulatory and Memory T Cells Specific for Immunodominant Gluten Epitopes of Celiac Disease. AB - Celiac disease (CD) is an HLA-associated disorder characterized by a harmful T cell response to dietary gluten. It is not understood why most individuals who carry CD-associated HLA molecules, such as HLA-DQ2.5, do not develop CD despite continuous gluten exposure. In this study, we have used tetramers of HLA-DQ2.5 bound with immunodominant gluten epitopes to explore whether HLA-DQ2.5(+) healthy individuals mount a specific CD4(+) T cell response to gluten. We found that gluten tetramer-binding memory cells were rare in blood of healthy individuals. These cells showed lower tetramer-binding intensity and no signs of biased TCR usage compared with gluten tetramer-binding memory T cells from patients. After sorting and in vitro expansion, only 18% of the tetramer-binding memory cells from healthy subjects versus 79% in CD patients were gluten-reactive upon tetramer restaining. Further, T cell clones of tetramer-sorted memory cells of healthy individuals showed lower gluten-specific proliferative responses compared with those of CD patients, indicating that tetramer-binding memory cells in healthy control subjects may be cross-reactive T cells. In duodenal biopsy specimens of healthy control subjects, CD4(+) T cells were determined not to be gluten reactive. Finally, gluten tetramer-binding cells of healthy individuals did not coexpress regulatory T cell markers (Foxp3(+) CD25(+)) and cultured T cell clones did not express a cytokine profile that indicated immune-dampening properties. The results demonstrate that healthy HLA-DQ2.5(+) individuals do not mount a T cell response to immunodominant gluten epitopes of CD. PMID- 26895835 TI - Loss of Fancc Impairs Antibody-Secreting Cell Differentiation in Mice through Deregulating the Wnt Signaling Pathway. AB - Fanconi anemia (FA) is characterized by a progressive bone marrow failure and an increased incidence of cancer. FA patients have high susceptibility to immune related complications such as infection and posttransplant graft-versus-host disease. In this study, we investigated the effect of FA deficiency in B cell function using the Fancc mouse model. Fancc(-/-) B cells show a specific defect in IgG2a switch and impaired Ab-secreting cell (ASC) differentiation. Global transcriptome analysis of naive B cells by mRNA sequencing demonstrates that FA deficiency deregulates a network of genes involved in immune function. Significantly, many genes implicated in Wnt signaling were aberrantly expressed in Fancc(-/-) B cells. Consistently, Fancc(-/-) B cells accumulate high levels of beta-catenin under both resting and stimulated conditions, suggesting hyperactive Wnt signaling. Using an in vivo Wnt GFP reporter assay, we verified the upregulation of Wnt signaling as a potential mechanism responsible for the impaired Fancc(-/-) B cell differentiation. Furthermore, we showed that Wnt signaling inhibits ASC differentiation possibly through repression of Blimp1 and that Fancc(-/-) B cells are hypersensitive to Wnt activation during ASC differentiation. Our findings identify Wnt signaling as a physiological regulator of ASC differentiation and establish a role for the Wnt pathway in normal B cell function and FA immune deficiency. PMID- 26895836 TI - Vitamin D [1,25(OH)2D3] Differentially Regulates Human Innate Cytokine Responses to Bacterial versus Viral Pattern Recognition Receptor Stimuli. AB - Vitamin D plays multiple roles in regulation of protective and maladaptive immunity. Although epidemiologic studies link poor in vivo 25(OH)D status to increased viral respiratory infections, we poorly understand how vitamin D affects viral pattern recognition receptor (PRR)-driven cytokine production. In this study, we hypothesized that the biologically active metabolite of vitamin D, 1,25(OH)2D3, inhibits human proinflammatory and anti-inflammatory innate cytokine responses stimulated by representative bacterial or viral PRR ligands. Fresh PBMCs or CD14(+) monocytes were stimulated with TLR4, TLR7/8-selective ligands, or respiratory syncytial virus (RSV) +/- 1,25(OH)2D3. Proinflammatory and anti inflammatory responses resulting from TLR4 stimulation were inhibited ~50% in the presence of 1,25(OH)2D3. Conversely, its usage at physiologic through pharmacologic concentrations inhibited neither proinflammatory nor anti inflammatory responses evoked by viral PRR ligands or infectious RSV. This differential responsiveness was attributed to the finding that TLR7/8, but not TLR4, stimulation markedly inhibited vitamin D receptor mRNA and protein expression, selectively reducing the sensitivity of viral PRR responses to modulation. 1,25(OH)2D3 also enhanced expression of IkBa, a potent negative regulator of NF-kappaB and cytokine production, in TLR4-stimulated monocytes while not doing so upon TLR7/8 stimulation. Thus, 1,25(OH)2D3 inhibits both proinflammatory and a broad panel of anti-inflammatory responses elicited by TLR4 stimulation, arguing that the common view of it as an anti-inflammatory immune response modifier is an oversimplification. In viral responses, it consistently fails to modify TLR7/8- or RSV-stimulated innate cytokine production, even at supraphysiologic concentrations. Collectively, the data call into question the rationale for increasingly widespread self-medication with vitamin D supplements. PMID- 26895839 TI - Differences in Physical and Psychosocial Characteristics Between CFS and Fatigued Non-CFS Patients, a Case-Control Study. AB - PURPOSE: The main research question is: "Do CFS patients differ from fatigued non CFS patients with respect to physical, cognitive, behavioral, social, and emotional determinants?" In addition, group differences in relevant outcomes were explored. METHOD: Patients who met the Centers for Disease Control (CDC) criteria for CFS were categorized as CFS; these patients were mainly recruited via a large Dutch patient organization. Primary care patients who were fatigued for at least 1 month and up to 2 years but did not meet the CDC criteria were classified as fatigued non-CFS patients. Both groups were matched by age and gender (N = 192 for each group). RESULTS: CFS patients attributed their fatigue more frequently to external causes, reported a worse physical functioning, more medical visits, and a lower employment rate. The results of a multiple logistic regression analysis showed that patients who believe that their fatigue is associated with more severe consequences, that their fatigue will last longer and is responsible for more additional symptoms are more likely to be classified as CFS, while patients who are more physically active and have higher levels of "all or nothing behavior" are less likely to be classified as having CFS. CONCLUSION: A longitudinal study should explore the predictive value of the above factors for the transition from medically unexplained fatigue to CFS in order to develop targeted interventions for primary care patients with short-term fatigue complaints. PMID- 26895840 TI - The Relationships Between Victim Age, Gender, and Relationship Polymorphism and Sexual Recidivism. AB - Victim choice polymorphism refers to victim inconsistency in a series of offenses by the same perpetrator, such as in the domains of victim age, victim gender, and victim-offender relationship. Past studies have found that victim age polymorphic offenders have higher rates of sexual recidivism than offenders against adults only and offenders against children only. Few studies, however, have examined gender and relationship polymorphism, or accounted for the impact of the number of past victims. The present study analyzed the relationship between polymorphism and sexual recidivism, while controlling for the number of victims. The sample consisted of 751 male adult sexual offenders followed for an average of 10 years, 311 of whom were polymorphic (41% of the total sample). The main finding suggested that there was an association between sexual recidivism and age and relationship polymorphism; however, these associations were no longer significant after controlling for the number of victims. PMID- 26895837 TI - Type I IFN Does Not Promote Susceptibility to Foodborne Listeria monocytogenes. AB - Type I IFN (IFN-alpha/beta) is thought to enhance growth of the foodborne intracellular pathogen Listeria monocytogenes by promoting mechanisms that dampen innate immunity to infection. However, the type I IFN response has been studied primarily using methods that bypass the stomach and, therefore, fail to replicate the natural course of L. monocytogenes infection. In this study, we compared i.v. and foodborne transmission of L. monocytogenes in mice lacking the common type I IFN receptor (IFNAR1(-/-)). Contrary to what was observed using i.v. infection, IFNAR1(-/-) and wild-type mice had similar bacterial burdens in the liver and spleen following foodborne infection. Splenocytes from wild-type mice infected i.v. produced significantly more IFN-beta than did those infected by the foodborne route. Consequently, the immunosuppressive effects of type I IFN signaling, which included T cell death, increased IL-10 secretion, and repression of neutrophil recruitment to the spleen, were all observed following i.v. but not foodborne transmission of L. monocytogenes. Type I IFN was also previously shown to cause a loss of responsiveness to IFN-gamma through downregulation of the IFN gamma receptor alpha-chain on macrophages and dendritic cells. However, we detected a decrease in surface expression of IFN-gamma receptor alpha-chain even in the absence of IFN-alpha/beta signaling, suggesting that in vivo, this infection-induced phenotype is not type I IFN-dependent. These results highlight the importance of using the natural route of infection for studies of host pathogen interactions and suggest that the detrimental effects of IFN-alpha/beta signaling on the innate immune response to L. monocytogenes may be an artifact of the i.v. infection model. PMID- 26895838 TI - Factors influencing completion of multi-dose vaccine schedules in adolescents: a systematic review. AB - BACKGROUND: Completion of multiple dose vaccine schedules is crucial to ensure a protective immune response, and maximise vaccine cost-effectiveness. While barriers and facilitators to vaccine uptake have recently been reviewed, there is no comprehensive review of factors influencing subsequent adherence or completion, which is key to achieving vaccine effectiveness. This study identifies and summarises the literature on factors affecting completion of multi dose vaccine schedules by adolescents. METHODS: Ten online databases and four websites were searched (February 2014). Studies with analysis of factors predicting completion of multi-dose vaccines were included. Study participants within 9-19 years of age were included in the review. The defined outcome was completion of the vaccine series within 1 year among those who received the first dose. RESULTS: Overall, 6159 abstracts were screened, and 502 full texts were reviewed. Sixty one studies were eligible for this review. All except two were set in high-income countries. Included studies evaluated human papillomavirus vaccine, hepatitis A, hepatitis B, and varicella vaccines. Reported vaccine completion rates, among those who initiated vaccination, ranged from 27% to over 90%. Minority racial or ethnic groups and inadequate health insurance coverage were risk factors for low completion, irrespective of initiation rates. Parental healthcare seeking behaviour was positively associated with completion. Vaccine delivery in schools was associated with higher completion than delivery in the community or health facilities. Gender, prior healthcare use and socio-economic status rarely remained significant risks or protective factors in multivariate analysis. CONCLUSIONS: Almost all studies investigating factors affecting completion have been carried out in developed countries and investigate a limited range of variables. Increased understanding of barriers to completion in adolescents will be invaluable to future new vaccine introductions and the further development of an adolescent health platform. PROSPERO reg# CRD42014006765. PMID- 26895841 TI - The impact of the donors' and recipients' medical complications on living kidney donors' mental health. AB - A minority of living kidney donors (between 5-25%) have poor psychological outcomes after donation. There is mixed evidence on the influence of medical complications on these outcomes. We examined whether medical complications among donors and recipients predicted changes in donors' mental health (psychological symptoms and well-being) between predonation and 1 year postdonation. One-hundred and forty-five donors completed questionnaires on mental health predonation and 3 and 12 months postdonation. Number of recipient rehospitalizations and donor complications (none; minor; or severe) were obtained from medical records at 3 and 12 months after surgery. Multilevel regression analyses were used to examine the association between medical complications and changes in donors' mental health over time after controlling for sociodemographic characteristics. We found that donor complications (P = 0.003) and recipient rehospitalizations (P = 0.001) predicted an increase in donors' psychological symptoms over time. Recipient rehospitalizations also predicted a decrease in well-being (P = 0.005) over time; however, this relationship became weaker over time. We conclude that medical complications experienced by either the donor or recipient is a risk factor for deterioration in donors' mental health after living kidney donation. Professionals should monitor donors who experience medical complications and offer additional psychological support when needed. PMID- 26895842 TI - The use of clinical practice guidelines in primary care: professional mindlines and control mechanisms. AB - OBJECTIVE: To identify the relevant barriers and enablers perceived by primary care professionals in implementing the recommendations of clinical practice guidelines (CPG). METHODS: Two focus groups were conducted with primary care physicians and nurses in Catalonia (Spain) between October and December 2012. Thirty-nine health professionals were selected based on their knowledge and daily use of CPG. Finally, eight general practitioners and eight nurses were included in the discussion groups. Participants were asked to share their views and beliefs on the accessibility of CPG, their knowledge and use of these documents, the content and format of CPG, dissemination strategy, training, professional patient relationship, and the use of CPG by the management structure. We recorded and transcribed the content verbatim and analysed the data using qualitative analysis techniques. RESULTS: Physicians believed that, overall, CPG were of little practical use and frequently referred to them as a largely bureaucratic management control instrument that threatened their professional autonomy. In contrast, nurses believed that CPG were rather helpful tools in their day-to-day practice, although they would like them to be more sensitive to the current role of nurses. Both groups believed that CPG did not provide a response to most of the decisions they faced in the primary care setting. CONCLUSIONS: Compliance with CPG recommendations would be improved if these documents were brief, non compulsory, not cost-containment oriented, more based on nursing care models, sensitive to the specific needs of primary care patients, and integrated into the computer workstation. PMID- 26895843 TI - Within- and across-breed genomic prediction using whole-genome sequence and single nucleotide polymorphism panels. AB - BACKGROUND: Currently, genomic prediction in cattle is largely based on panels of about 54k single nucleotide polymorphisms (SNPs). However with the decreasing costs of and current advances in next-generation sequencing technologies, whole genome sequence (WGS) data on large numbers of individuals is within reach. Availability of such data provides new opportunities for genomic selection, which need to be explored. METHODS: This simulation study investigated how much predictive ability is gained by using WGS data under scenarios with QTL (quantitative trait loci) densities ranging from 45 to 132 QTL/Morgan and heritabilities ranging from 0.07 to 0.30, compared to different SNP densities, with emphasis on divergent dairy cattle breeds with small populations. The relative performances of best linear unbiased prediction (SNP-BLUP) and of a variable selection method with a mixture of two normal distributions (MixP) were also evaluated. Genomic predictions were based on within-population, across population, and multi-breed reference populations. RESULTS: The use of WGS data for within-population predictions resulted in small to large increases in accuracy for low to moderately heritable traits. Depending on heritability of the trait, and on SNP and QTL densities, accuracy increased by up to 31 %. The advantage of WGS data was more pronounced (7 to 92 % increase in accuracy depending on trait heritability, SNP and QTL densities, and time of divergence between populations) with a combined reference population and when using MixP. While MixP outperformed SNP-BLUP at 45 QTL/Morgan, SNP-BLUP was as good as MixP when QTL density increased to 132 QTL/Morgan. CONCLUSIONS: Our results show that, genomic predictions in numerically small cattle populations would benefit from a combination of WGS data, a multi-breed reference population, and a variable selection method. PMID- 26895844 TI - Comparative investigation of the mutagenicity of propenylic and allylic asarone isomers in the Ames fluctuation assay. AB - alpha-, beta- and gamma-asarone are naturally occurring phenylpropenes that occur in different plant families, mainly in Aristolochiaceae, Acoraceae and Lauraceae. Plants containing asarones are used as flavouring ingredients in alcoholic beverages (bitters), traditional phytomedicines and the rhizome of e.g. Acorus calamus is used to prepare tea. Although alpha- and beta-asarone show a potential in the treatment of several diseases, previous studies have shown carcinogenicity in rodents (duodenum, liver). However, the mechanism of action remained unclear. Studies on the mutagenicity of propenylic alpha- and beta-asarone are inconsistent and data on carcinogenicity and genotoxicity of allylic gamma asarone are lacking completely. Thus, the present study determined the mutagenicity of the three asarone isomers using the Ames fluctuation assay with and without exogenous metabolic activation (S9 mix) in the standard Salmonella typhimurium strains TA98 and TA100. A concentration dependent increase in mutagenicity could be verified for alpha- and beta-asarone in strain TA100 in the presence of rat liver homogenate. The side-chain epoxides of alpha- and beta asarone, major metabolites formed in liver microsomes, caused mutations in TA100, supporting the hypothesis that epoxidation of the side chain plays a key role in mutagenicity of the propenylic alkenylbenzenes. The allylic gamma-asarone, not undergoing detectable side-chain epoxidation in liver microsomes, was supposed to be activated via side-chain hydroxylation and further sulphonation, a typical pathway for other allylic alkenylbenzenes like estragole or methyleugenol. However, neither y-asarone nor 1'-OH-gamma-asarone showed any mutagenic effect even in the human SULT-expressing Salmonella strains (TA100-hSULT1A1 and TA100 hSULT1C2), while 1'-OH-methyleugenol used as a positive control was mutagenic under these conditions. These results indicate that the propenylic asarones are genotoxic via metabolic formation of side-chain epoxides while the side-chain hydroxylation/sulphonation pathway is either not operative or does not lead to mutagenicity with the allylic gamma-asarone. PMID- 26895845 TI - Disturbances in Response Inhibition and Emotional Processing as Potential Pathways to Violence in Schizophrenia: A High-Density Event-Related Potential Study. AB - OBJECTIVE: Increased susceptibility to emotional triggers and poor response inhibition are important in the etiology of violence in schizophrenia. Our goal was to evaluate abnormalities in neurophysiological mechanisms underlying response inhibition and emotional processing in violent patients with schizophrenia (VS) and 3 different comparison groups: nonviolent patients (NV), healthy controls (HC) and nonpsychotic violent subjects (NPV). METHODS: We recorded high-density Event-Related Potentials (ERPs) and behavioral responses during an Emotional Go/NoGo Task in 35 VS, 24 NV, 28 HC and 31 NPV subjects. We also evaluated psychiatric symptoms and impulsivity. RESULTS: The neural and behavioral deficits in violent patients were most pronounced when they were presented with negative emotional stimuli: They responded more quickly than NV when they made commission errors (ie, failure of inhibition), and evidenced N2 increases and P3 decreases. In contrast, NVs showed little change in reaction time or ERP amplitude with emotional stimuli. These N2 and P3 amplitude changes in VSs showed a strong association with greater impulsivity. Besides these group specific changes, VSs shared deficits with NV, mostly N2 reduction, and with violent nonpsychotic subjects, particularly P3 reduction. CONCLUSION: Negative affective triggers have a strong impact on violent patients with schizophrenia which may have both behavioral and neural manifestations. The resulting activation could interfere with response inhibition. The affective disruption of response inhibition, identified in this study, may index an important pathway to violence in schizophrenia and suggest new modes of treatment. PMID- 26895847 TI - Effect of Adding Online Social Support Tools to an Adult Walking Program: A Pilot Randomized Controlled Trial. AB - This pilot study examined the efficacy of providing access to online social support tools on adults' step counts during a technology-mediated walking intervention. Sixty-three insufficiently active adults were randomized to a 12 week walking intervention with (SUPPORT) or without (NO SUPPORT) access to online social support tools. Both groups received a pedometer, step goals, and access to relevant websites. The SUPPORT group also received access to online social support tools. A mixed-factor analysis of variance was conducted to examine within- and between-group differences in measures of daily steps, psychosocial indicators, and health. Both groups significantly (p < .05) increased their daily steps over time from baseline by 1,401 (SUPPORT) and 2,461 (NO SUPPORT), with no significant differences between groups. Psychosocial and health improvements were no greater for SUPPORT versus NO SUPPORT. The SUPPORT group's use of the online social support tools was low. Results suggest that giving adults access to online social support tools during a technology-mediated walking program did not lead to an enhanced increase in daily steps versus an identical program without these tools; however, the low use of these tools may have weakened their effect. Future studies should examine SUPPORT versus NO SUPPORT among groups with preexisting social ties. PMID- 26895846 TI - Who benefits from orthogeriatric treatment? Results from the Trondheim hip fracture trial. AB - BACKGROUND: Hip fracture patients are heterogenous. Certain patient characteristics are associated with poorer prognosis, but less is known about differences in response to treatment among subgroups. The Trondheim Hip Fracture trial found beneficial effects on mobility and function from comprehensive geriatric care (CGC) compared to traditional orthopaedic care (OC). The aim of this study was to explore differences in response to CGC among subgroups in this trial. METHODS: Secondary analysis of the complete dataset from Trondheim Hip Fracture Trial, a randomised controlled trial including 397 home-dwelling older adults (>=70 years) with a hip fracture. Subgroups were age (over/under 80 years), gender, fracture type (intra-/extracapsular), and pre-fracture instrumental ADL (i-ADL) (defined as over/under 45 on the Nottingham Extended ADL scale). Dependent variables were mobility (Short Physical Performance Battery), personal ADL (p-ADL) (Barthel Index), i-ADL (Nottingham Extended ADL scale), cognition (Mini-Mental Status Examination), four and 12 months after hip fracture. Data were analysed by linear mixed models with interactions (treatment, time, and subgroup), reporting treatment effects being clinically and statistically significant within and between subgroups. RESULTS: Analyses within subgroups showed beneficial effects of CGC on mobility and i-ADL either at four or twelve months in all subgroups except for males, extra-capsular fractures and patients with impaired pre-fracture i-ADL. Beneficial effect on p- ADL was found in patients < 80 years, intra-capsular fractures and patients with impaired pre fracture i-ADL. Effects on cognition were found in patients < 80 years and men. The interaction analyses showed that CGC had statistically significant better treatment effect on i-ADL for younger participants at four months (p = 0.004), on p-ADL both at four (p = 0.037) and twelve months (p = 0.045) and mobility at twelve months (p = 0.021), for participants with intracapsular as compared to extracapsular fractures, and on i-ADL at twelve months for participants with higher pre-fracture function (p = 0.012). CONCLUSION: Contrary to our hypothesis that the most vulnerable patients would benefit the most from CGC, we found the intervention effect was most pronounced in younger, female participants with higher pre-fracture i-ADL function. TRIAL RIGISTRATION: ClinicalTrials.gov registration number: NCT00667914. PMID- 26895848 TI - !Miranos! (Look at Us! We Are Healthy!): Home-Based and Parent Peer-Led Childhood Obesity Prevention. AB - Parent interventions for childhood obesity prevention have traditionally experienced low participation rates or used passive methods such as newsletters. In contrast, the !Miranos! intervention home-based activities included parent-led face-to-face meetings delivered after school, take-home bags with educational materials, and scavenger hunt games to deliver health information to Head Start families regarding nutrition, physical activity, and healthy growth promotion for their preschooler. This study employed a quasi-experimental design with three intervention centers (two that received only center-based activities and one that received center- and home-based activities) and one comparison center. Data were collected on participating Head Start children and their parents/guardians and included parent attendance, parent health message recall through intercept interviews, parent knowledge through pre- and posttests, and family supportive behaviors and child health behaviors through a parent questionnaire. Parents/guardians that received both center- and home-based activities significantly increased knowledge scores (t = 2.50, degrees of freedom = 123, p < .05) and family supportive behaviors from baseline to follow-up (t = 2.12, degrees of freedom = 122, p < .05). This study demonstrates the effects home based interventions can have when coupled with center-based activities and implemented in the center at the end of the school day. PMID- 26895850 TI - Zika Virus. PMID- 26895849 TI - Prevalence and patterns of traditional bullying victimization and cyber-teasing among college population in Spain. AB - BACKGROUND: Traditional bullying victimization and the growing number of cyber teasing victims during the last decade is a major public health concern. The objective of this study was to examine the relationship between students' experiences of traditional bullying victimization and cyber-teasing and the sociodemographic characteristics of a sample composed of college students in Spain. METHODS: In the fall of 2014, 543 sixth-grade students from southeast Spain completed an anonymous survey on their experience of both kinds of to ascertain any relationship with sociodemographic characteristics, including gender, nationality, economic problems, family conflicts and alcohol and cannabis use. RESULTS: A total of 62.2% of the students reported to having suffered traditional bullying victimization and 52.7% reported that they had been subject to cyber-teasing. 40.7% of participants had been victims of traditional bullying victimization and cyber-teasing in the past 12 months. Most (65.7%) of the victims were at the same time cyber-teasing victims; 77.6% of cyber-teasing victims were also victimized in a different manner. Traditional bullying victimization was higher among boys than among girls, while female students were more likely to have been subjected to cyber-teasing than male students. The characteristics that most heavily influenced suffering traditional bullying victimization were economic problems, family conflicts and cannabis use. CONCLUSIONS: Our findings confirm overlapping results in the risk factors that influence suffering both traditional bullying victimization and cyber-teasing: there was a strong influence of certain sociodemographic and individual characteristics of the college population, suggesting that specific policies are necessary to improve college students' environment in Spain. PMID- 26895851 TI - Expression and prognostic significance of ELL-associated factor 2 in human prostate cancer. AB - PURPOSE: ELL-associated factor 2 (EAF2) is an androgen-regulated tumor suppressor in the prostate. The purpose of this study was to investigate the expression of EAF2 protein in human prostate cancer specimens along with BPH specimens as a control, and to evaluate potential association of EAF2 expression with clinical characteristics and overall survival of the prostate cancer patients. METHODS: The expression of EAF2 was evaluated in 44 prostate cancer and 23 BPH tissue specimens using immunohistochemistry. The relationships of EAF2 expression with clinical characteristics and overall survival rates were analyzed by Chi-square test and Kaplan-Meier method. RESULTS: The immunostaining intensity of EAF2 in BPH specimens was significantly higher than that in prostate cancer (p < 0.05). EAF2 expression decreased significantly in high-grade and advanced-stage human prostate tumors and inversely correlated with PSA level, Gleason scores, bone metastasis and tumor stage. Importantly, loss of EAF2 expression was associated with a significant decrease in patient survival. CONCLUSION: Expression of EAF2 is decreased in prostate carcinogenesis, and EAF2 loss is associated with high risk patients and poor survival. PMID- 26895852 TI - Comparison of renal functional outcomes in exactly matched pairs between robot assisted partial nephrectomy using warm ischemia and open partial nephrectomy using cold ischemia using diethylene triamine penta-acetic acid renal scintigraphy. AB - PURPOSE: To compare renal functional outcomes in patients with a small renal mass undergoing robot-assisted partial nephrectomy using warm ischemia (wRAPN) or open partial nephrectomy using cold ischemia (cOPN). METHODS: This study included 185 patients who underwent partial nephrectomy and were assessed by preoperative and postoperative diethylene triamine penta-acetic acid renal scintigraphy. Variables associated with postoperative operated-side glomerular filtration rate decrement (DeltaGFR) were assessed using multivariate analysis. Exact 1:1 propensity score matching was performed using variables related to DeltaGFR. Furthermore, 30 patients who underwent wRAPN were matched with 30 patients who underwent cOPN, and their differences in DeltaGFR were calculated. RESULTS: Patients who underwent cOPN were older (p = 0.025) and had shorter ischemia time (p < 0.001) than patients who underwent wRAPN. Multivariate analysis showed that surgical method, preoperative operated-side GFR and RENAL nephrometry score were significantly associated with operated-side DeltaGFR. After propensity score matching, postoperative 3-month (14.8 vs. 7.3 mL/min/1.73 m(2), p = 0.057) and 1 year operated-side DeltaGFR (11.4 vs. 2.8 mL/min/1.73 m(2), p = 0.031) was higher after wRAPN than after cOPN in patients with ischemia time >=25 min, but did not differ in patients with ischemia time <25 min. Within the matched pairs, cOPN resulted in lower operated-side DeltaGFR than wRAPN in patients with ischemia time >=25 min (-6.9 mL/min/1.73 m(2), p = 0.047). Moreover, total GFR decrement was slightly lower with cOPN than with wRAPN (-7.2 mL/min/1.73 m(2), p = 0.086). CONCLUSIONS: cOPN was superior to wRAPN in patients with a small renal mass and ischemia time >=25 min. However, wRAPN yielded renal functional outcomes comparable to those of cOPN when ischemia time was <25 min. PMID- 26895853 TI - Test-Retest Reliability of Isokinetic Knee Strength Measurements in Children Aged 8 to 10 Years. AB - BACKGROUND: Isokinetic dynamometry is a useful tool to objectively assess muscle strength of children and adults in athletic and rehabilitative settings. This study examined test-retest reliability of isokinetic knee strength measurements in children aged 8 to 10 years and defined limits for the minimum difference (MD) in strength that indicates a clinically important change. HYPOTHESIS: Isokinetic knee strength measurements (using the Biodex System 4) in children will provide reliable results. STUDY DESIGN: Descriptive laboratory study. METHODS: In 22 healthy children, 5 maximal concentric (CON) knee extensor (KE) and knee flexor (KF) contractions at 2 angular velocities (60 deg/s and 180 deg/s) and 5 maximal eccentric (ECC) KE/KF contractions at 60 deg/s were assessed 7 days apart. The intraclass correlation coefficient (ICC2.1) was used to examine relative reliability, and the MD was calculated on the basis of standard error of measurement. RESULTS: ICCs for CON KE/KF peak torque measurements were fair to excellent (range, 0.49-0.81). The MD% values for CON KE and KF ranged from 31% to 37% at 60 deg/s and from 34% to 39% at 180 deg/s. ICCs in the ECC mode were good (range, 0.60-0.70), but associated MD% values were high (>50%). There was no systematic error for CON KE/KF and ECC KE strength measurements at 60 deg/s, but systematic error was found for all other measurements. CONCLUSION: The dynamometer provides a reliable analysis of isokinetic CON knee strength measurements at 60 deg/s in children aged 8 to 10 years. Measurements at 180 deg/s and in the ECC mode were not reliable, indicating a need for more familiarization prior to testing. CLINICAL RELEVANCE: The MD values may help clinicians to determine whether a change in knee strength is due to error or intervention. PMID- 26895854 TI - Erratum to: Purification and characterization of a cytochrome c with novel caspase-3 activation activity from the pathogenic fungus Rhizopus arrhizus. PMID- 26895856 TI - Culture, role conflict and caregiver stress: The lived experiences of family cancer caregivers in Nairobi. AB - This article explores the experiences of a small group of Nairobi women caring for a family cancer patient at home. On the basis of literature on women as caregivers in Africa, and on other literature more broadly, it was anticipated that issues around generational roles, gender and women's cultural role would be relevant. Seven women participated in semi-structured in-depth interviews, while thirteen women participated in four mini focus groups. Data were analysed using interpretative phenomenological analysis. Findings underscore the socio-cultural complexities of caregiving as a basis for evidence-based culturally appropriate structures to support family caregivers. PMID- 26895855 TI - Functional performance, nutritional status, and body composition in ambulant community-dwelling individuals 1-3 years after suffering from a cerebral infarction or intracerebral bleeding. AB - BACKGROUND: Muscle wasting and obesity may complicate the post-stroke trajectory. We investigated the relationships between nutritional status, body composition, and mobility one to 3 years after stroke. METHODS: Among 279 eligible home dwelling individuals who had suffered a stroke (except for subarachnoid bleeding) 1-3 years earlier, 134 (74 +/- 5 years, 69% men) were examined according to the Mini Nutritional Assessment-Short Form (MNA-SF, 0-14 points), including body mass index (BMI, kg/m(2)), body composition by bio-impedance analyses (Tanita BC-545), the Short Physical Performance Battery (SPPB, 0-12 points) combining walking speed, balance, and chair stand capacity, and the self-reported Physical Activity Scale for the Elderly (PASE). RESULTS: BMI >= 30 kg/m(2) was observed in 22% of cases, and 14% were at risk for malnutrition according to the MNA-SF. SPPB scores <= 8 in 28% of cases indicated high risk for disability. Mobility based on the SPPB was not associated with the fat-free mass index (FFMI) or fat mass index (FMI). Multivariate logistic regression indicated that low mobility, i.e., SPPB <= 8 points, was independently related to risk for malnutrition (OR 4.3, CI 1.7 10.5, P = 0.02), low physical activity (PASE) (OR 6.5, CI 2.0-21.2, P = 0.02), and high age (OR 0.36, CI 0.15-0.85, P = 0.02). Sarcopenia, defined as a reduced FFMI combined with SPPB scores <= 8 or reduced gait speed (<1 m/s), was observed in 7% of cases. None of the individuals displayed sarcopenic obesity (SO), defined as sarcopenia with BMI > 30 kg/m(2). CONCLUSIONS: Nutritional disorders, i.e., obesity, sarcopenia, or risk for malnutrition, were observed in about one third of individuals 1 year after stroke. Risk for malnutrition, self-reported physical activity, and age were related to mobility (SPPB), whereas fat-free mass (FFM) and fat mass (FM) were not. Nutrition and exercise treatment could be further evaluated as rehabilitation opportunities after stroke. PMID- 26895857 TI - Enhancement of D-lactic acid production from a mixed glucose and xylose substrate by the Escherichia coli strain JH15 devoid of the glucose effect. AB - BACKGROUND: A thermal tolerant stereo-complex poly-lactic acid (SC-PLA) can be made by mixing Poly-D-lactic acid (PDLA) and poly-L-lactic acid (PLLA) at a defined ratio. This environmentally friendly biodegradable polymer could replace traditional recalcitrant petroleum-based plastics. To achieve this goal, however, it is imperative to produce optically pure lactic acid isomers using a cost effective substrate such as cellulosic biomass. The roadblock of this process is that: 1) xylose derived from cellulosic biomass is un-fermentable by most lactic acid bacteria; 2) the glucose effect results in delayed and incomplete xylose fermentation. An alternative strain devoid of the glucose effect is needed to co utilize both glucose and xylose for improved D-lactic acid production using a cellulosic biomass substrate. RESULTS: A previously engineered L-lactic acid Escherichia coli strain, WL204 (DeltafrdBC DeltaldhA DeltaackA DeltapflB DeltapdhR ::pflBp6-acEF-lpd DeltamgsA DeltaadhE, DeltaldhA::ldhL), was reengineered for production of D-lactic acid, by replacing the recombinant L lactate dehydrogenase gene (ldhL) with a D-lactate dehydrogenase gene (ldhA). The glucose effect (catabolite repression) of the resulting strain, JH13, was eliminated by deletion of the ptsG gene which encodes for IIBC(glc) (a PTS enzyme for glucose transport). The derived strain, JH14, was metabolically evolved through serial transfers in screw-cap tubes containing glucose. The evolved strain, JH15, regained improved anaerobic cell growth using glucose. In fermentations using a mixture of glucose (50 g L(-1)) and xylose (50 g L(-1)), JH15 co-utilized both glucose and xylose, achieving an average sugar consumption rate of 1.04 g L(-1)h(-1), a D-lactic acid titer of 83 g L(-1), and a productivity of 0.86 g L(-1) h(-1). This result represents a 46 % improved sugar consumption rate, a 26 % increased D-lactic acid titer, and a 48 % enhanced productivity, compared to that achieved by JH13. CONCLUSIONS: These results demonstrated that JH15 has the potential for fermentative production of D-lactic acid using cellulosic biomass derived substrates, which contain a mixture of C6 and C5 sugars. PMID- 26895858 TI - Inactivation of the global regulator LaeA in Monascus ruber results in a species dependent response in sporulation and secondary metabolism. AB - The nuclear regulator LaeA has been proven to globally govern fungal development and secondary metabolism, but its function may be species-dependent, even though its amino acid sequences are well conserved in numerous fungi. Herein we identified the LaeA in Monascus ruber M7 (MrLaeA), and verified its role to mediate growth, sporulation and secondary metabolism. Results showed that the radial growth rate of the selected MrlaeA knock-out mutant (MrDeltalaeA-22) was significantly faster than that of the parental strain M. ruber M7, and growth was accompanied by the formation of an abnormal colony phenotype with more abundant aerial hyphae. Interestingly, conidia production of the MrDeltalaeA-22 strain was about thrice that of M. ruber M7, but ascospores were not observed in the MrDeltalaeA-22 strain. Additionally, compared to M. ruber M7, MrDeltalaeA-22 exhibited drastically reduced production of multiple secondary metabolites, especially those of the six well-known Monascus pigments and citrinin. Simultaneously, the selected MrlaeA complementation strain (MrDeltalaeA::laeA-45) nearly recovered the capacity for sporulation and secondary metabolism observed in the parental strain. These results demonstrate that MrLaeA regulates not only secondary metabolism, but also asexual and sexual differentiation in M. ruber, but some of its regulation appears to differ from other fungi. PMID- 26895859 TI - Putative identification of the usnic acid biosynthetic gene cluster by de novo whole-genome sequencing of a lichen-forming fungus. AB - To identify the biosynthetic gene cluster responsible for the biosynthesis of the polyketide usnic acid we carried out the de novo genome sequencing of the fungal partner of Cladonia uncialis. This was followed by comprehensive in silico annotation of polyketide synthase (PKS) genes. The biosynthesis of usnic acid requires a non-reducing PKS possessing a carbon methylation (CMeT) domain, a terminal Claisen cyclase (CLC) domain, and an accompanying oxidative enzyme that dimerizes methylphloracetophenone to usnic acid. Of the 32 candidate PKS genes identified in the mycobiont genome, only one was identified as consistent with these biosynthetic requirements. This gene cluster contains two genes encoding a non-reducing PKS and a cytochrome p450, which have been respectively named methylphloracetophenone synthase (MPAS) and methylphloracetophenone oxidase (MPAO). Both mpas and mpao were demonstrated to be transcriptionally active by reverse transcriptase-PCR of the mRNA in a lichen sample that was observed by HPLC to produce usnic acid. Phylogenetic analysis of the bioinformatically identified ketosynthase (KS) and CLC domains of MPAS demonstrated that mpas grouped within a unique clade and that mpas could be used as a phylogenetic probe to identify other MPAS genes. PMID- 26895860 TI - Disruption of ku70 involved in non-homologous end-joining facilitates homologous recombination but increases temperature sensitivity in the phytopathogenic fungus Penicillium digitatum. AB - The dominant mechanism to repair double-stranded DNA breaks in filamentous fungi is the non-homologous end joining (NHEJ) pathway, and not the homologous recombination (HR) pathway that operates in the mutation of genes by replacement of target DNA for selection cassettes. The key to improve HR frequency is the inactivation of the NHEJ pathway by eliminating components of its Ku70/80 heterodimeric complex. We have obtained ku70 mutants of Penicillium digitatum, the main citrus postharvest pathogen. The increased efficiency of HR in Deltaku70 strains was demonstrated by the generation of mutants in two different chitin synthase genes (PdchsII and PdchsV). P. digitatum Deltaku70 strains showed no differences from the parental strain in vegetative growth, asexual development or virulence to citrus fruit, when experiments were conducted at the optimal temperature of 24 degrees C. However, growth of Deltaku70 strains at temperatures higher than 24 degrees C demonstrated a detrimental effect in axenic growth and conidia production. These observations are in agreement with previous studies describing differences between ku70 mutants and their parental strains in some fungal species, and must be taken into account for future applications of the Deltaku approach to increase HR efficiency in fungi. PMID- 26895861 TI - An ultrastructural study of Paraphysoderma sedebokerense (Blastocladiomycota), an epibiotic parasite of microalgae. AB - Successful algal cultivation for biofuel production is one path in the transition to a renewable energy economy. The green alga Scenedesmus dimorphus is a candidate for biofuel production, but is subject to parasitism and subsequent population crash when cultivated in open ponds. From an open pond cultivating S. dimorphus for biofuel production in New Mexico, USA, an amoeboid parasite was isolated, designated as isolate FD61, and its rDNA operon sequenced. A BLAST search for nuc 18S rDNA (18S) sequence similarity identified the parasite as Paraphysoderma sedebokerense (Blastocladiomycota). Here, we examine the ultrastructure of P. sedebokerense and compare it with that of a sister taxon, Physoderma maydis. The parasite has thin-walled vegetative sporangia and thick walled resting sporangia. Our observations indicate that amoeboid swarmers are produced in the vegetative phase, while either amoeboid swarmers or zoospores are the product of meiosis in resting sporangia. Meiosis is confirmed by the presence of synaptonemal complexes in resting sporangia nuclei. Notably, P. sedebokerense has a Golgi apparatus with stacked cisternae, a feature reported for P. maydis, but which is absent in all other examined taxa in Blastocladiomycota. This report furthers our knowledge of the life cycle of P. sedebokerense. PMID- 26895862 TI - Novel mitoviruses in Rhizoctonia solani AG-3PT infecting potato. AB - Double-stranded RNA (dsRNA) elements are ubiquitous in Rhizoctonia solani. Total dsRNA was randomly amplified from a R. solani isolate (RS002) belonging to anastomosis group-3PT (AG-3PT), associated with black scurf in potato. Assembly of resulting cDNA sequences identified a nearly complete genome of a novel virus related to the genus Mitovirus (family Narnaviridae), herein named Rhizoctonia mitovirus 1 RS002 (RMV-1-RS002). The 2797 nucleotide partial genome of RMV-1 RS002 is A-U rich (59.06 %), and can be folded into stable stem-loop structures at 5' and 3' ends. Universal and mold mitochondrial codon usages revealed a large open reading frame in the genome, putatively encoding an 826 amino acid polypeptide, which has conserved motifs for mitoviral RNA-dependent RNA polymerase. The full length putative polypeptide shared 25.6 % sequence identity with the corresponding region of Tuber excavatum mitovirus (TeMV). The partial genome of a second mitovirus (proposed name Rhizoctonia mitovirus 2 RS002 (RMV-2 RS002)) was also amplified from RS002. A nearly identical copy of RMV-1-RS002 was detected in two additional AG-3PT isolates. These data indicate that multiple mitoviruses can exist in a single isolate of R. solani AG-3PT, and that mitoviruses such as RMV-1-RS002 are probably widespread in this pathogen. The roles of mitoviruses in the biology of R. solani AG-3PT remain unknown. PMID- 26895863 TI - Occurrence and transmission of mycovirus Cryphonectria hypovirus 1 from dejecta of Thyreophagus corticalis (Acari, Acaridae). AB - The natural spread of virus-induced hypovirulence is highly involved in the recovery of blighted chestnut stands and orchards in Italy and in Europe. The potential role of corticolous mites as vectors of hypovirulence in blighted chestnut Castanea sativa (Mill.) stands was pointed out in previous reports. Here, by using RT-PCR, mycovirus Cryphonectria hypovirus (CHV1) was detected in Thyreophagus corticalis mites reared on a hypovirulent strain in monoxenic cultures and in their faecal pellets. Cryphonectria parasitica mycelium derived from mites' dejecta was able to transmit CHV1 to the virulent strain determining its conversion to hypovirulent one. This converted strain induced healing cankers on excised stems, differently from the un-converted virulent strain. Our findings prove the spread of CHV1 by corticolous mites that feed on virus-infected fungus and emphasize their potential role as vectors. PMID- 26895864 TI - Characterization of three distinct metallothionein genes of the Ag hyperaccumulating ectomycorrhizal fungus Amanita strobiliformis. AB - Mechanisms evolved in eukaryotes to handle heavy metals involve cytosolic, metal binding metallothioneins (MTs). We have previously documented that the sequestration of silver (Ag) in the Ag-hyperaccumulating Amanita strobiliformis is dominated by 34-amino-acid (AA) AsMT1a, 1b, and 1c isoforms. Here we show that in addition to AsMT1a, 1b, and 1c isogenes, the fungus has two other MT genes: AsMT2 encoding a 34-AA AsMT2 similar to MTs known from other species, but unrelated to AsMT1s; AsMT3 coding for a 62-AA AsMT3 that shares substantial identity with as-yet-uncharacterized conserved peptides predicted in agaricomycetes. Transcription of AsMT1s and AsMT3 in the A. strobiliformis mycelium was specifically inducible by treatments with Ag or copper (Cu) and zinc (Zn) or cadmium (Cd), respectively; AsMT2 showed a moderate upregulation in the presence of Cd. Expression of AsMTs in the metal-sensitive Saccharomyces cerevisiae revealed that all AsMTs confer increased Cd tolerance (AsMT3 proved the most effective) and that, unlike AsMT1 and AsMT2, AsMT3 can protect the yeasts against Zn toxicity. The highest level of Cu tolerance was observed with yeasts expressing AsMT1a. Our data indicate that A. strobiliformis can specifically employ different MT genes for functions in the cellular handling of Ag and Cu (AsMT1s) and Zn (AsMT3). PMID- 26895865 TI - Assimilation of organic and inorganic nutrients by Erica root fungi from the fynbos ecosystem. AB - Erica dominate the fynbos ecosystem, which is characterized by acidic soils that are rich in organic matter. The ericaceae associate with ericoid mycorrhizal (ERM) fungi for survival. In this study fungal biomass accumulation in vitro was used to determine nutrient utilisation of various inorganic and organic substrates. This is an initial step towards establishment of the ecological roles of typical ERM fungi and other root fungi associated with Erica plants, with regard to host nutrition. Meliniomyces sp., Acremonium implicatum, Leohumicola sp., Cryptosporiopsis erica, Oidiodendron maius and an unidentified Helotiales fungus were selected from fungi previously isolated and identified from Erica roots. Sole nitrogen sources ammonium, nitrate, arginine and Bovine Serum Albumin (BSA) were tested. Meliniomyces and Leohumicola species were able to utilise BSA effectively. Phosphorus nutrition was tested using orthophosphate, sodium inositol hexaphosphate and DNA. Most isolates preferred orthophosphate. Meliniomyces sp. and A. implicatum were able to accumulate significant biomass using DNA. Carbon utilisation was tested using glucose, cellobiose, carboxymethylcellulose, pectin and tannic acid substrates. All fungal isolates produced high biomass on glucose and cellobiose. The ability to utilize organic nutrient sources in culture, illustrates their potential role of these fungi in host nutrition in the fynbos ecosystem. PMID- 26895866 TI - Genome organisation and expression profiling of ABC protein-encoding genes in Heterobasidion annosum s.l. complex. AB - Members of Heterobasidion annosum species complex are widely regarded as the most destructive fungal pathogens of conifer trees in the boreal and temperate zones of Northern hemisphere. To invade and colonise their host trees, Heterobasidion fungi must overcome components of host chemical defence, including terpenoid oleoresin and phenolic compounds. ABC transporters may play an important role in this process participating in the export of toxic host metabolites and maintaining their intracellular concentration below the critical level. We have identified and phylogenetically classified Heterobasidion genes encoding ABC transporters and closely related ABC proteins. The number of ABC proteins in the Heterobasidion genome is one of the lowest among analysed species of Agaricomycotina. Using quantitative RT-PCR, we have analysed transcriptional response of Heterobasidion ABC transporter-encoding genes to monoterpenes as well as their expression profile during growth on pine wood in comparison to the growth on defined media. Several ABC transporters were up-regulated during growth on pine wood. The ABC-transporter encoding gene ABCG1.1 was induced both during growth of H. annosum on pine wood and upon exposure to monoterpenes. Our experimental data demonstrate the differential responses of Heterobasidion ABC genes to growth conditions and chemical stressors. The presented results suggest a potential role of Heterobasidion ABC-G transporters in the resistance to the components of conifer chemical defence. PMID- 26895867 TI - High genotypic diversity found among population of Phytophthora infestans collected in Estonia. AB - Potato late blight, caused by the oomycete pathogen Phytophthora infestans, is one of the most important diseases of potato worldwide. This is the first study characterising Estonian P. infestans population using the SSR marker genotyping method. 70 P. infestans isolates collected during the growing season in 2004 from eight potato fields in three different regions of Estonia were characterised with nine polymorphic SSR markers. A1 and A2 mating type isolates were detected from every studied field indicating the high potential for sexual reproduction, which raises the genotypic diversity in P. infestans population. Results revealed highly diverse P. infestans population in Estonia resembling the Northern European populations. Most of the multilocus genotypes were detected only once among the collected isolates. Subpopulations collected from different geographical regions of Estonia showed no differentiation from each other but instead formed one highly diverse group. PMID- 26895868 TI - Food preparation with mucoralean fungi: A potential biosafety issue? AB - Mucorales have been used for production of fermented food in Asia and Africa since time immemorial. Particularly Rhizopus species are rapidly growing, active producers of lipases and proteases and occur naturally during the first stages of soybean fermentation. Two biosafety issues have been raised in recent literature: (1) pathogenicity, Rhizopus species being prevalent opportunists causing erosive infections in severely compromised patients, and (2) toxicity, strains harbouring endosymbiotic Burkholderia producing toxic secondary metabolites. At the molecular level, based on different gene markers, species identity was found between strains used for food processing and clinical strains. In this study, we screened for bacterial symbionts in 64 Rhizopus strains by light microscopy, 16S rRNA sequencing, and HPLC. Seven strains (11 %) carried bacteria identified as Burkholderia rhizoxinica and Burkholderia endofungorum, and an unknown Burkholderia species. The Burkholderia isolates proved to be able to produce toxic rhizoxins. Strains with endosymbionts originated from food, soil, and a clinical source, and thus their presence could not be linked to particular habitats. The presence of Burkholderia in Rhizopus producing toxins could not be excluded as a potential risk for human health. In contrast, given the type of diseases caused by Rhizopus species, we regard the practical risk of infection via the food industry as negligible. PMID- 26895869 TI - Potential of endophytic fungus Phomopsis liquidambari for transformation and degradation of recalcitrant pollutant sinapic acid. AB - The biodegradation potential of sinapic acid, one of the most representative methoxy phenolic pollutants presented in industrial wastewater, was first studied using an endophytic fungus called Phomopsis liquidambari. This strain can effectively degrade sinapic acid in flasks and in soil and the possible biodegradation pathway was first systematically proposed on the basis of the metabolite production patterns and the identification of the metabolites by GC-MS and HPLC-MS. Sinapic acid was first transformed to 2,6-dimethoxy-4-vinylphenol that was further degraded via 4-hydroxy-3,5-dimethoxybenzaldehyde, syringic acid, gallic acid, and citric acid which involved in the continuous catalysis by phenolic acid decarboxylase, laccase, and gallic acid dioxygenase. Moreover, their activities and gene expression levels exhibited a 'cascade induction' response with the changes in metabolic product concentrations and the generation of fungal laccase significantly improved the degradation process. This study is the first report of an endophytic fungus that has great potential to degrade xenobiotic sinapic acid, and also provide a basis for practical application of endophytic fungus in the bioremediation of sinapic acid-contaminated industrial wastewater and soils. PMID- 26895870 TI - Species clarification of Isaria isolates used as biocontrol agents against Diaphorina citri (Hemiptera: Liviidae) in Mexico. AB - Entomopathogenic fungi belonging to the genus Isaria (Hypocreales: Cordycipitaceae) are promising candidates for microbial control of insect pests. Currently, the Mexican government is developing a biological control program based on extensive application of Isaria isolates against Diaphorina citri (Hemiptera: Liviidae), a vector of citrus huanglongbing disease. Previous research identified three promising Isaria isolates (CHE-CNRCB 303, 305, and 307; tentatively identified as Isaria fumosorosea) from Mexico. The goal of this work was to obtain a complete morphological and molecular characterization of these isolates. Comparative analysis of morphology established that the isolates showed similar characteristics to Isaria javanica. Multi-gene analysis confirmed the morphological identification by including the three isolates within the I. javanica clade. Additionally, this work demonstrated the misidentifications of three other Isaria isolates (CHE-CNRCB 310 and 324: I. javanica, formerly I. fumosorosea; CHE-CNRCB 393: I. fumosorosea, formerly Isaria farinosa), underlying the need for a full and correct characterization of an isolate before developing a biological control program. Finally, the inter-simple sequence repeat (ISSR) genotyping method revealed that the CHE-CNRCB 303, 305, and 307 isolates belong to three different genotypes. This result indicates that ISSR markers could be used as a tool to monitor their presence in field conditions. PMID- 26895871 TI - Ascochyta blight: isolation, characterization, and development of a rapid method to detect inhibitors of the chickpea fungal pathogen Ascochyta rabiei. AB - Ascochyta blight is the major disease attacking chickpea (Cicer arietinum) around the world. Since its first time report of isolation in Argentina in 2012, the pathogen has caused severe economic losses and has acquired a great importance. We report here the isolation of Ascochyta rabiei from infected chickpea beans cultivated in Santa Fe, Argentina; its identification by morphological analysis and molecular biology techniques based on internal transcribed spacer (ITS) sequence alignment, its biochemical characterization regarding the capacity to produce proteinase and phospholipase enzymes, and its antifungal susceptibility to common used antifungal agents. In order to detect new inhibitors for A. rabiei from natural sources, a bioautographic method was developed. From the screening method developed, we found that extracts from cultures of Aspergillus parasiticus are active against A. rabiei. PMID- 26895872 TI - Plant growth-promoting traits of yeasts isolated from the phyllosphere and rhizosphere of Drosera spatulata Lab. AB - Microorganisms can promote plant growth through direct and indirect mechanisms. Compared with the use of bacteria and mycorrhizal fungi, the use of yeasts as plant growth-promoting (PGP) agents has not been extensively investigated. In this study, yeast isolates from the phyllosphere and rhizosphere of the medicinally important plant Drosera spatulata Lab. were assessed for their PGP traits. All isolates were tested for indole-3-acetic acid-, ammonia-, and polyamine-producing abilities, calcium phosphate and zinc oxide solubilizing ability, and catalase activity. Furthermore, the activities of siderophore, 1 aminocyclopropane-1-carboxylate deaminase, and fungal cell wall-degrading enzymes were assessed. The antagonistic action of yeasts against pathogenic Glomerella cingulata was evaluated. The cocultivation of Nicotiana benthamiana with yeast isolates enhanced plant growth, indicating a potential yeast-plant interaction. Our study results highlight the potential use of yeasts as plant biofertilizers under controlled and field conditions. PMID- 26895873 TI - Further Defining the Role of the Laboratory Genetic Counselor. AB - Laboratory genetic counseling is becoming increasingly common as a result of increased laboratory services and genetic testing menus, as well as growing job responsibilities. Christian et al. (2012) provided the first quantitative data regarding the roles of the laboratory-based genetic counselor (LBGC) finding that two of the most prevalent roles are as customer liaisons and communicators of test results. The goal of the present study was to further delineate the role of the LBGC by addressing specific tasks that LBGCs are involved with on a day-to day basis. A survey was designed to expand upon themes identified in the Christian et al. (2012) study by querying specific tasks performed in several categories of potential LBGC job duties. An invitation for LBGCs to participate was distributed via email to the membership of the National Society of Genetic Counselors (NSGC) and the Canadian Association of Genetic Counsellors (CAGC). We identified 121 genetic counselors who primarily work in the laboratory setting or whose job role includes a laboratory component. Almost all respondents performed customer liaison/case coordination (95 %), and interpretation and result reporting (88 %). The most frequently performed tasks within these categories involved addressing questions from clients, making phone calls with genetic testing results, obtaining clinical or family history information for results interpretation, and composing case-specific interpretations for unique results and/or obtaining literature references to support interpretations. The study results also point to trends of expanding roles in sales and marketing, variant interpretation and management responsibilities. Results of this study may be useful to further define the full scope of practice of LBGCs, aid in the development of new LBGC positions and expand current positions to include roles related to test development, research, and student supervision. It may also aid in curriculum updates for training programs to increase exposure to LBGC roles. PMID- 26895875 TI - [Genodermatoses associated with increased risk of cutaneous carcinoma: New entities]. PMID- 26895874 TI - [Extensive vulvar pigmentation]. PMID- 26895876 TI - Gestational age and birthweight for risk assessment of neurodevelopmental impairment or death in extremely preterm infants. AB - BACKGROUND: The risk of poor outcomes in preterm infants is primarily determined by birthweight (BW) and gestational age (GA). It is not known whether BW is a better outcome predictor than GA. OBJECTIVE: To test whether BW is better than GA (measured in days, rather than completed weeks) for prediction of neurodevelopmental impairment (NDI) and death. DESIGN/METHODS: Extremely preterm infants born at the National Institute of Child Health and Human Development (NICHD) Neonatal Research Network centres between 1998 and 2009 were studied. For the unadjusted analysis, the associations of GA (in days based on best obstetrical estimate) and BW (in grams) with NDI or death were compared using area under the curve (AUC). Adjusted analyses were performed using birth year, sex, race, antenatal steroids, singleton birth, pre-eclampsia, Apgar score at 5 min and small for GA as covariates. RESULTS: 10 652 preterm infants (89%) had outcome data at 18-22 months' corrected age. The mean BW was 678 g (SD: 155) and the mean GA was 173 days (SD: 10) or 245/7 weeks (SD: 13/7). The AUC for NDI or death was 80% with BW and 79% with GA (p=0.82). Unadjusted and adjusted analyses did not differ. NDI or death rates decreased with increasing GA through 26 weeks (estimated risk reduction with each additional day of gestation: 2.2%). CONCLUSION: Both BW in grams and GA in days are good predictors of NDI and death in a preterm population selected on the basis of reliable GA. TRIAL REGISTRATION NUMBER: NCT00009633. PMID- 26895879 TI - Point-of-care tests using enzyme detection to diagnose Chlamydia trachomatis infection do not work. But when they fail in clinical trials, they reappear under different names. PMID- 26895878 TI - Are adolescents with high self-esteem protected from psychosomatic symptomatology? AB - This study investigated the role of self-esteem, social (need to belong, loneliness, competitiveness, and shyness), and health (smoking, drinking) behaviors in Hungarian adolescents' psychosomatic symptoms. Our sample of 490 students (ages 14-19 years) from Debrecen (Hungary) completed the questionnaires. Besides descriptive statistics, correlation and multiple regression analyses were applied to test interrelationships. Frequency analysis revealed that fatigue was the most commonly experienced psychosomatic symptom in this sample, followed by sleeping problems and (lower) back pain. Girls reported experiencing more symptoms. Multiple regression analyses suggested that (1) need to belong, shyness, and competitiveness may serve as social behavioral risk factors for adolescents' psychosomatic symptomatology, whereas (2) self-esteem may play a protective role. The role of social and health behaviors was modified when analyzed by gender: the psychosomatic index score was positively related to smoking and shyness among girls, and need to belong among boys. Self-esteem provided protection for both sexes. CONCLUSION: We conclude that problems with social relationships (namely, unmet need to belong, competitiveness, and shyness) may lead to psychosomatic health complaints, whereas self-esteem may serve as a protection. Findings suggest that social skills training and strengthening self esteem should be an important part of children's health promotion programs in schools to improve their psychosomatic health and well-being. WHAT IS KNOWN: * Despite being free of serious physical illness, many adolescents often report subjective health complaints, such as psychosomatic symptoms * As children in this life stage develop independence and autonomy, new types of social relationships, and identity, their social needs and skills also change What is new: * Need to belong, shyness, and competitiveness may serve as social behavioral risk factors for adolescents' psychosomatic symptomatology, whereas self-esteem may play a protective role * The role of social and health behaviors may vary by gender. PMID- 26895877 TI - "Nihilism" of chronic heart failure therapy in children and why effective therapy is withheld. AB - Major advances in chronic heart failure (cHF) therapy have been achieved and documented in adult patients, while research regarding the mechanisms and therapy of cHF in children has lagged behind. Based on receptor physiological studies and pharmacological knowledge, treatment with specific beta1-adrenergic receptor blocker (ARB), tissue angiotensin-converting enzyme inhibitor (ACE-I), and mineralocorticoid antagonists have to be recommended in children despite lack of sufficient data derived from prospective randomized studies. At our institution, bisoprolol, lisinopril, and spironolactone have been firmly established to treat systolic cHF, hypoplastic left heart syndrome (HLHS) following hybrid approach and congenital left-right shunt diseases, latest in patients where surgery has to be delayed. Chronic therapy with long-acting diuretics and fluid restriction are not advocated because short-term effects are achieved at the expense of further neuro-humoral stimulation. It remains unclear why diuretics are recommended although evidence-based studies, documenting long-term benefit, are missing. However, that is true for all currently used drugs for pediatric cHF. CONCLUSION: This review focuses on the prevailing "nihilism" of cHF therapy in children with the goal to encourage physicians to treat pediatric cHF with a rationally designed therapy, which combines available agents that have been shown to improve survival in adult patients with cHF. Because of the lack of clinical trials, which generate the needed evidence, surrogate variables like heart and respiratory rate, weight gain, image-derived data, and biomarkers should be monitored and used instead. The recommended pharmacological therapy for systolic heart failure is also provided as the basis for utilizing reversible pulmonary arterial banding (PAB) as a novel strategy in young children with dilative cardiomyopathy (DCM) with preserved right ventricular function. WHAT IS KNOWN: * Heart failure (HF) in children is a serious public health concern. * HF has numerous etiologies, but unspecific symptoms. * HF interplays among neuro humoral, and molecular abnormalities. * Pediatric cHF-therapy is currently based on loop-diuretics, fluid restriction and digoxin. What is New: * Cardiac function analysis has to include cardiac synchrony and VVI. * Considering enormous potential of cardiac regeneration, therapy has to extend with selective beta1 ARB, tissue ACE-I and mineralocorticoid blockers, loop-diuretics avoided as ever possible. * Inhibition of the endogenous neuro-humoral stimulation is monitored by surrogate parameters as heart and breath rate and systolic and diastolic blood pressure. * Advocated HF therapy serves for regenerative strategies as reversible Pulmonary Artery Banding in DCM. PMID- 26895881 TI - Does Rapid and Sustained Economic Growth Lead to Convergence in Health Resources: The Case of China From 1980 to 2010. AB - China's rapid and sustained economic growth offers an opportunity to ask whether the advantages of growth diffuse throughout an economy, or remain localized in areas where the growth has been the greatest. A critical policy area in China has been the health system, and health inequality has become an issue that has led the government to broaden national health insurance programs. This study investigates whether health system resources and performance have converged over the past 30 years across China's 31 provinces. To examine geographic variation of health system resources and performance at the provincial level, we measure the degree of sigma convergence and beta convergence in indicators of health system resources (structure), health services utilization (process), and outcome. All data are from officially published sources: the China Health Statistics Year Book and the China Statistics Year Book. Sigma convergence is found for resource indicators, whereas it is not observed for either process or outcome indicators, indicating that disparities only narrowed in health system resources. Beta convergence is found in most indicators, except for 2 procedure indicators, reflecting that provinces with poorer resources were catching up. Convergence found in this study probably reflects the mixed outcome of government input, and market forces. Thus, left alone, the equitable distribution of health care resources may not occur naturally during a period of economic growth. Governmental and societal efforts are needed to reduce geographic health variation and promote health equity. PMID- 26895880 TI - Plague in China 2014-All sporadic case report of pneumonic plague. AB - BACKGROUND: Yersinia pestis is the pathogen of the plague and caused three pandemics worldwide. Pneumonic plague is rarer than bubonic and septicemic plague. We report detailed clinical and pathogenic data for all the three sporadic cases of pneumonic plagues in China in 2014. CASE PRESENTATION: All the three patients are herders in Gansu province of China. They were all infected by Yersinia pestis and displayed in the form of pneumonic plague respectively without related. We tested patient specimens from the upper (nasopharyngeal swabs) or the lower (sputum) respiratory tract and whole blood, plasma, and serum specimens for Yersinia pestis. All patients had fever, cough and dyspnea, and for patient 2 and 3, unconscious. Respiratory symptoms were predominant with acute respiratory failure. The chest X-ray showed signs consistent with necrotizing inflammation with multiple lobar involvements. Despite emergency treatment, all patients died of refractory multiple organ failure within 24 h after admission to hospital. All the contacts were quarantined immediately and there were no secondary cases. CONCLUSIONS: Nowadays, the plague is epidemic in animals and can infect people who contact with the infected animals which may cause an epidemic in human. We think dogs maybe an intermediate vector for plague and as a source of risk for humans who are exposed to pet animals or who work professionally with canines. If a patient has been exposed to a risk factor and has fever and dyspnea, plague should be considered. People who had contact with a confirmed case should be isolated and investigated for F1 antigen analysis and receive post exposure preventive treatment. A vaccination strategy might be useful for individuals who are occupationally exposed in areas where endemically infected reservoirs of plague-infected small mammals co-exist. PMID- 26895882 TI - Strengthening pharmaceutical systems for palliative care services in resource limited settings: piloting a mHealth application across a rural and urban setting in Uganda. AB - BACKGROUND: Medicine availability is improving in sub-Saharan Africa for palliative care services. There is a need to develop strong and sustainable pharmaceutical systems to enhance the proper management of palliative care medicines, some of which are controlled. One approach to addressing these needs is the use of mobile technology to support data capture, storage and retrieval. Utilizing mobile technology in healthcare (mHealth) has recently been highlighted as an approach to enhancing palliative care services but development is at an early stage. METHODS: An electronic application was implemented as part of palliative care services at two settings in Uganda; a rural hospital and an urban hospice. Measures of the completeness of data capture, time efficiency of activities and medicines stock and waste management were taken pre- and post implementation to identify changes to practice arising from the introduction of the application. RESULTS: Improvements in all measures were identified at both sites. The application supported the registration and management of 455 patients and a total of 565 consultations. Improvements in both time efficiency and medicines management were noted. Time taken to collect and report pharmaceuticals data was reduced from 7 days to 30 min and 10 days to 1 h at the urban hospice and rural hospital respectively. Stock expiration reduced from 3 to 0.5% at the urban hospice and from 58 to 0% at the rural hospital. Additional observations relating to the use of the application across the two sites are reported. CONCLUSIONS: A mHealth approach adopted in this study was shown to improve existing processes for patient record management, pharmacy forecasting and supply planning, procurement, and distribution of essential health commodities for palliative care services. An important next step will be to identify where and how such mHealth approaches can be implemented more widely to improve pharmaceutical systems for palliative care services in resource limited settings. PMID- 26895883 TI - Association Between Plasma Uric Acid Levels and Cardiorenal Function in Adolescents With Type 1 Diabetes. AB - OBJECTIVE: The relationship between plasma uric acid (PUA) and renal and cardiovascular parameters in adolescents with type 1 diabetes (T1D) is not well understood. Our aims in this exploratory analysis were to study the association between PUA and estimated glomerular filtration rate (eGFR), urinary albumin-to creatinine ratio (ACR), blood pressure, endothelial function, and arterial stiffness in T1D adolescents. These associations were also studied in healthy control (HC) subjects. RESEARCH DESIGN AND METHODS: We studied 188 T1D subjects recruited to the Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT) and 65 HC subjects. Baseline PUA, eGFRcystatin C, ACR, blood pressure, flow-mediated dilation (FMD), and carotid-femoral pulse wave velocity (PWV) were measured. RESULTS: PUA was lower in T1D vs. HC subjects (242 +/- 55 vs. 306 +/- 74 MUmol/L, respectively; P < 0.0001). Higher PUA was inversely associated with eGFR in T1D subjects (r = -0.48, P < 0.0001) even after correction for baseline clinical demographic characteristics. PUA was not associated with ACR in T1D after adjustment for potential confounders such as eGFR. For cardiovascular parameters, PUA levels did not associate with systolic blood pressure, FMD, or PWV in T1D or HC subjects. CONCLUSIONS: Even within the physiological range, PUA levels were significantly lower in T1D adolescent patients compared with HC subjects. There was an inverse relationship between PUA and eGFR in T1D, likely reflecting an increase in clearance. There were no associations observed with ACR, blood pressure, arterial stiffness, or endothelial function. Thus, in contrast with adults, PUA may not yet be associated with cardiorenal abnormalities in adolescents with T1D. PMID- 26895884 TI - Branched-Chain Amino Acids and Insulin Metabolism: The Insulin Resistance Atherosclerosis Study (IRAS). AB - OBJECTIVE: Recent studies using untargeted metabolomics approaches have suggested that plasma branched-chain amino acids (BCAAs) are associated with incident diabetes. However, little is known about the role of plasma BCAAs in metabolic abnormalities underlying diabetes and whether these relationships are consistent across ethnic populations at high risk for diabetes. We investigated the associations of BCAAs with insulin sensitivity (SI), acute insulin response (AIR), and metabolic clearance of insulin (MCRI) in a multiethnic cohort. RESEARCH DESIGN AND METHODS: In 685 participants without diabetes of the Insulin Resistance Atherosclerosis Study (IRAS) (290 Caucasians, 165 African Americans, and 230 Hispanics), we measured plasma BCAAs (sum of valine, leucine, and isoleucine) by mass spectrometry and SI, AIR, and MCRI by frequently sampled intravenous glucose tolerance tests. RESULTS: Elevated plasma BCAAs were inversely associated with SI and MCRI and positively associated with fasting insulin in regression models adjusted for potential confounders (beta = -0.0012 [95% CI -0.0018, -0.00059], P < 0.001 for SI; beta = -0.0013 [95% CI -0.0018, 0.00082], P < 0.001 for MCRI; and beta = 0.0015 [95% CI 0.0008, 0.0023], P < 0.001 for fasting insulin). The association of BCAA with SI was significantly modified by ethnicity, with the association only being significant in Caucasians and Hispanics. Elevated plasma BCAAs were associated with incident diabetes in Caucasians and Hispanics (multivariable-adjusted odds ratio per 1-SD increase in plasma BCAAs: 1.67 [95% CI 1.21, 2.29], P = 0.002) but not in African Americans. Plasma BCAAs were not associated with SI-adjusted AIR. CONCLUSIONS: Plasma BCAAs are associated with incident diabetes and underlying metabolic abnormalities, although the associations were generally stronger in Caucasians and Hispanics. PMID- 26895885 TI - Effects of Frequency of Sensor-Augmented Pump Use on HbA1c and C-Peptide Levels in the First Year of Type 1 Diabetes. PMID- 26895886 TI - Immunohistochemical Labelling for Cyclo-oxygenase-2: Does the Positive Control Guarantee Standardized Results? AB - Since the identification of cyclo-oxygenase-2 as a potentially important therapeutic target in veterinary oncology, numerous studies on its expression have been conducted. Unfortunately, results have been heterogeneous and conclusions are difficult to draw. We tested the ability of a defined positive control to guarantee reproducibility of results among different laboratories. Valid positive controls were defined by positivity of the renal macula densa without background labelling. Fifteen colorectal tumours and 15 oral squamous cell carcinomas were labelled immunohistochemically by six European laboratories. Slides were evaluated in blinded fashion for percentage of positive cells and labelling intensity by three pathologists, and results were analyzed statistically for reproducibility and inter-reader variability. Macula densa positivity was an insufficiently sensitive control to guarantee reproducible results for percentage of positive cells and labelling intensity. Inter-reader variability was proven statistically, making the case for image analysis or other automated quantitative evaluation techniques. PMID- 26895887 TI - Cerebral Candidal Abscess and Bovine Viral Diarrhoea Virus Infection in an Aborted Bovine Fetus. AB - Candida species are opportunistic fungi associated with immunosuppression and are the most commonly isolated fungal pathogens from the human central nervous system. Invasive candidiasis is reported uncommonly in animals and there have only been two reports of candidal infection of the brain. This report presents a case of a cerebral candidal abscess in an aborted late-term calf co-infected with bovine viral diarrhoea virus. Candida etchellsii, a species not previously identified as pathogenic, was identified as the causative agent by polymerase chain reaction. PMID- 26895888 TI - Overexpression of Ephrin A3 Receptor in Canine Prostatic Carcinoma. AB - Ephrin A3 (EphA3), a member of the ephrin receptor tyrosine kinase family, is involved in a variety of functions in normal cells, especially during embryonic development, and alterations in its expression profile have been observed in several human cancers. However, there are no reports of the expression of EphA3 in normal, hyperplastic or neoplastic canine prostate tissue or in other types of canine tumours. Six normal, 15 hyperplastic and 21 neoplastic canine prostates were examined immunohistochemically with a polyclonal antibody specific for human EphA3. The percentage of positive cells in all prostatic carcinomas was increased, with a mean of 89.28 +/- 5.18% compared with normal (9.17 +/- 6.72%) and hyperplastic prostates (20.00 +/- 8.28%). EphA3 expression was not correlated with the histological subtypes of prostate cancer or with the Gleason score. The increase in EphA3 expression in canine prostatic carcinomas suggests the involvement of this receptor in prostatic carcinogenesis and its potential use as a target for new therapeutic strategies. PMID- 26895890 TI - DynaMIT: the dynamic motif integration toolkit. PMID- 26895889 TI - Delineation of metabolic gene clusters in plant genomes by chromatin signatures. AB - Plants are a tremendous source of diverse chemicals, including many natural product-derived drugs. It has recently become apparent that the genes for the biosynthesis of numerous different types of plant natural products are organized as metabolic gene clusters, thereby unveiling a highly unusual form of plant genome architecture and offering novel avenues for discovery and exploitation of plant specialized metabolism. Here we show that these clustered pathways are characterized by distinct chromatin signatures of histone 3 lysine trimethylation (H3K27me3) and histone 2 variant H2A.Z, associated with cluster repression and activation, respectively, and represent discrete windows of co-regulation in the genome. We further demonstrate that knowledge of these chromatin signatures along with chromatin mutants can be used to mine genomes for cluster discovery. The roles of H3K27me3 and H2A.Z in repression and activation of single genes in plants are well known. However, our discovery of highly localized operon-like co regulated regions of chromatin modification is unprecedented in plants. Our findings raise intriguing parallels with groups of physically linked multi-gene complexes in animals and with clustered pathways for specialized metabolism in filamentous fungi. PMID- 26895891 TI - Is laparoscopic surgery really effective for the treatment of colon and rectal cancer in very elderly over 80 years old? A prospective multicentric case-control assessment. AB - BACKGROUND: To evaluate the effectiveness of laparoscopic surgery (LCS) for colon and rectal cancer in the very elderly over 80 years old. METHODS: We performed a prospective multicentric analysis comparing patients over 80 years (Group A) and patients between 60 and 69 years (Group B) undergoing LCS for cancer from January 2008 to December 2013. Colon and rectal cancers were analyzed separately. Comorbidity and complications were classified using the Charlson comorbidity index (CCI) and the Clavien-Dindo system, respectively. Oncological parameters included tumor-free margins, number of lymph nodes harvested and circumferential resection margin. RESULTS: Group A included 96 and 33 patients, and Group B 220 and 82 for colon and rectal cancers, respectively. Groups were similar except for ASA score and CCI, as expected. There was no significant difference in operative time [colon; rectum] (180[IQR 150-200] vs 180[150-210] min; NS-180[160-210] vs 180[165-240] min; NS), estimated blood loss (50[25-75] vs 50[25-120] mL; NS-50[0 150] vs 50[25-108.7] mL; NS) and conversion rate (2.1 vs 2.7 %; NS-3.0 vs 2.4 %; NS). Timing of first stool (3[2-3.25] vs 3[2-5] dd; NS-3[2-4] vs 3[2-5] dd; NS), length of stay (7[6-8] vs 7[6-8] dd; NS-8[8-9] vs 8[7-9] dd; NS) and readmission rate (1.0 vs 0.45 %; NS-6.1 vs 1.2 %; NS) were similar. Tumor-free margins were appropriate, and positivity of CRM is poor (6.1 vs 4.9; NS). We did not record significant differences in complications rate (47.9 vs 43.6 %; NS-63.6 vs 52.4 %; NS). CONCLUSIONS: Laparoscopic surgery is effective for the treatment of colorectal cancer even in the very elderly. Age is not a risk factor or a limitation for LCS. PMID- 26895892 TI - Predictors for regional lymph node metastasis in T1 rectal cancer: a population based SEER analysis. AB - BACKGROUND: Local resection of early-stage rectal cancer significantly reduces perioperative morbidity compared with radical resection. Identifying patients at risk of regional lymph node metastasis (LNM) is crucial for long-term survival after local resection. METHODS: Patients after oncological resection of T1 rectal cancer were identified in the Surveillance, Epidemiology, and End Results register 2004-2012. Potential predictors of LNM and its impact on cancer-specific survival were assessed in logistic and Cox regression with and without multivariable adjustment. RESULTS: In total, 1593 patients with radical resection of T1 rectal cancer and a minimum of 12 retrieved regional lymph nodes were identified. The overall LNM rate was 16.3 % (N = 260). A low risk of LNM was observed for small tumor size (P = 0.002), low tumor grade (P = 0.002) and higher age (P = 0.012) in multivariable analysis. The odds ratio for a tumor size exceeding 1.5 cm was 1.49 [95 % confidence interval (CI) 1.06-2.13], for G2 and G3/G4 carcinomas 1.69 (95 % CI 1.07-2.82) and 2.72 (95 % CI 1.50-5.03), and for 65- to 79-year-old and over 80-year-old patients 0.65 (95 % CI 0.43-0.96) and 0.39 (95 % CI 0.18-0.77), respectively. Five-year cancer-specific survival for patients with LNM was 90.0 % (95 % CI 85.3-95.0 %) and for patients without LNM 97.1 % (95 % CI 95.9-98.2 %, hazard ratio = 3.21, 95 % CI 1.82-5.69, P < 0.001). CONCLUSIONS: In this population-based analysis, favorable cancer-specific survival rates were observed in nodal-negative and nodal-positive T1 rectal cancer patients after primary radical resection. The predictive value of tumor size, grading and age for LNM should be considered in medical decision making about local resection. PMID- 26895893 TI - The usefulness of 3-dimensional endoscope systems in endoscopic surgery. AB - BACKGROUND: The image quality and performance of 3-dimensional video image systems has improved along with improvements in technology. However, objective evaluation on the usefulness of 3-dimensional video image systems is insufficient. Therefore, we decided to investigate the usefulness of 3 dimensional video image systems using the objective endoscopic surgery technology evaluating apparatus that we have developed, the Hiroshima University Endoscopic Surgical Assessment Device (HUESAD). METHODS: The participants were 28 student volunteers enrolled in Hiroshima University (17 men and 11 women, age: median 22.5, range 20-25), with no one having experienced endoscopic surgery training. Testing was carried out by dividing the subjects into two groups to initially carry out HUESAD with 2-dimensional video imaging (N = 14) and with 3-dimensional video imaging (N = 14). Questionnaires were carried out along with the investigation regarding both 2-dimensional and 3-dimensional video imaging. The task was carried out for approximately 15 min regarding both 2-dimensional and 3 dimensional video imaging. Lastly, the Mental Rotation Test, which is a standard space perception ability test, was used to evaluate the space perception ability. RESULTS: No difference was observed in the nauseous and uncomfortable feeling of practitioners between the two groups. Regarding smoothness, no difference was observed between 2-dimensional and 3-dimensional video imaging (p = 0.8665). Deviation (space perception ability) and approaching time (accuracy) were significantly lower with 3-dimensional video imaging compared to 2-dimensional video imaging. Moreover, the approaching time (accuracy) significantly improved in 3-dimensional video imaging compared to 2-dimensional video imaging in the group with low space perception ability (p = 0.0085). CONCLUSION: Objective evaluation using HUESAD and subjective evaluation by questionnaire revealed that endoscopic surgery techniques significantly improved in 3-dimensional video imaging compared to 2-dimensional video imaging. Moreover, it is believed that this effect is more effective in people with low space perception ability and beginner students. PMID- 26895894 TI - Effect of bowel resection on TLR signaling during intestinal adaptation in a rat model. AB - BACKGROUND: Bacterial overgrowth is common complication of short bowel syndrome (SBS) and is a result of an impaired gut barrier function. Toll-like receptor 4 (TLR4) is crucial in maintaining intestinal epithelial homeostasis, participates in a vigorous signaling process and heightens inflammatory cytokine output. The objective of this study was to determine the effects of bowel resection on TLR4 signaling in intestinal mucosa in a rat model. METHODS: Male Sprague-Dawley rats were randomly assigned to one of the two experimental groups of eight rats each: Sham rats underwent bowel transection and re-anastomosis and SBS rats underwent 75 % small bowel resection. Rats were killed on day 14. Bacterial translocation (BT) to mesenteric lymph nodes, liver, portal blood and peripheral blood was determined at the kill. The expression of TLR4, MyD88 and TRAF6 in the intestinal mucosa was determined using real-time PCR, Western blot and immunohistochemistry. RESULTS: SBS rats demonstrated a 100 % BT to lymph nodes and to liver (Level I), 80 % translocation to portal blood (Level II) and 60 % translocation to peripheral blood (Level III) at day 7 as well as a 100 % BT to lymph nodes and liver, and 40 % translocation to peripheral blood at day 14. Microarray expression profiling demonstrated that most of the TLR signaling-related genes were up-regulated in resected rats compared to control animals. SBS rats showed a significant increase in TLR4 and TRAF6 mRNA in jejunum and ileum, TLR4 and MyD88 protein expression in jejunum and ileum, and a significant increase in the number of TLR4 and TRAF6 positive cells (immunohistochemistry) compared to sham animals. CONCLUSIONS: In a rat model of SBS, elevated intestinal BT is associated with a stimulated TLR4 signaling. PMID- 26895897 TI - Factors affecting dilation force in balloon dilation of severe esophageal strictures: an experiment using an artificial stricture model. AB - BACKGROUND: The multidiameter balloon catheter is used widely for severe esophageal stricture dilation. However, the relationships between inflation pressure, balloon size, and radial dilation force at the stricture site have not been examined fully. METHODS: We performed an experiment using phantom models to investigate the relationships between inflation pressure, balloon size, and radial dilation force. The balloon dilation procedure was performed for each stricture model using three sizes of balloon: 10-11-12, 12-13.5-15, and 15-16.5 18 mm. RESULTS: A positive association between inflation pressure and dilation force was observed for each balloon size. In balloons inflated by targeting the same diameter, the dilation force was higher for smaller balloons than for larger balloons. An inverse association between stricture size and dilation force was observed in the 12-13.5-15 mm balloon (3 vs 5 mm, P = .002; 5 vs 7 mm, P < .001). CONCLUSIONS: We found relationships between inflation pressure, balloon size, severity of strictures, and dilation force. To perform safe and effective esophageal balloon dilation, the inflation pressure and balloon size should be selected after considering the stricture size and target diameter. PMID- 26895895 TI - Closure with clips to accelerate healing of mucosal defects caused by colorectal endoscopic submucosal dissection. AB - BACKGROUND: Most mucosal defects that occur with endoscopic submucosal dissection (ESD) can be closed completely using endoscopic clips. However, benefits of such closure in wound healing are unknown. A randomized controlled study evaluated the efficacy of closure with clips compared with no closure. METHOD: Twenty-eight patients who had undergone ESD were randomly divided into two groups: closure (n = 14) and non-closure groups (n = 14). In the closure group, the mucosal defect resulting from ESD was closed using endoscopic clips. Four weeks after ESD, defects in both groups were observed by colonoscopy. Efficacy was based on change in the area of the defect, percentage of complete healing in each group, and complications. RESULT: Data were analyzed for 26 of the 28 patients (13, closure group; 13, non-closure group). All tumors were resected en bloc by ESD without bleeding or perforation. In the closure group, the area of the defect just after ESD was 677 +/- 306 mm(2) (mean +/- SD) as determined by the size of the removed lesion and had decreased to 2.17 +/- 4.51 mm(2) at 4 weeks after ESD (reduction, 99.7 %), but in the non-closure group that area was 790 +/- 221 mm(2) and had decreased to 27.42 +/- 25.72 mm(2) at 4 weeks post-ESD (reduction, 96.2 %). The reduction rate was significantly higher in the closure than in the non-closure group (99.7 vs. 96.2 %, p = 0.010). Complete healing was 69.2 % in the closure group vs. 7.7 % in the non-closure group (p = 0.005). Multivariate analysis showed that closure of the mucosal defect (OR 24.029, 95 % CI 2.09-276.15, p = 0.011) was an independent factor associated with complete healing at 4 weeks after ESD. Delayed perforation or post-ESD bleeding was not observed in any participant. CONCLUSION: Use of endoscopic clips for closure of defects after ESD is safe and efficacious in accelerating wound healing. TRIAL REGISTRATION: UMIN CTR UMIN000009112. PMID- 26895898 TI - Vessel sealing comparison: old school is still hip. AB - BACKGROUND: Ligation with either absorbable or non-absorbable sutures has been the traditional state of the art, but a proliferation of technology now offers a host of methods to close and divide vessels. Only limited data are available that objectively compare different vessel sealing methods. The objective of this study was to compare a broad variety of methods of surgical vessel closure in a reproducible, independent, standardized test-to-failure ex vivo pressure challenge. METHODS: Ten of the most common surgical sealing devices were represented in this study, including both mechanical and energy devices. Unfixed porcine carotid arteries were selected for testing. They were connected to a pump, and automated controlled infusion was initiated. Upon identification of a leak at the source of sealing, the maximum pressure in mmHg was logged. RESULTS: There were a total of 184 trials conducted using the 10 vessel sealing methods. The average burst pressure across all trials was 1100 mmHg with a range of 51.3 5171 mmHg. Suture-based methods displayed the highest average pressure until failure. Stapling methods showed the lowest burst pressures. All methods showed mean burst pressures above the "physiologically relevant" level of 250 mmHg. CONCLUSIONS: This study presents an independent, reproducible, ex vivo comparison of multiple methods of surgical arterial closure. In these laboratory conditions, tests to failure demonstrated widely varying sealing strength, highly dependent on method. All hemostatic modalities tested are capable of securing vessels safely and well above physiologic blood pressures, while suture-based methods were significantly stronger than other mechanical methods or modern energy devices. PMID- 26895896 TI - Robotic surgery: disruptive innovation or unfulfilled promise? A systematic review and meta-analysis of the first 30 years. AB - BACKGROUND: Robotic surgery has been in existence for 30 years. This study aimed to evaluate the overall perioperative outcomes of robotic surgery compared with open surgery (OS) and conventional minimally invasive surgery (MIS) across various surgical procedures. METHODS: MEDLINE, EMBASE, PsycINFO, and ClinicalTrials.gov were searched from 1990 up to October 2013 with no language restriction. Relevant review articles were hand-searched for remaining studies. Randomised controlled trials (RCTs) and prospective comparative studies (PROs) on perioperative outcomes, regardless of patient age and sex, were included. Primary outcomes were blood loss, blood transfusion rate, operative time, length of hospital stay, and 30-day overall complication rate. RESULTS: We identified 99 relevant articles (108 studies, 14,448 patients). For robotic versus OS, 50 studies (11 RCTs, 39 PROs) demonstrated reduction in blood loss [ratio of means (RoM) 0.505, 95 % confidence interval (CI) 0.408-0.602], transfusion rate [risk ratio (RR) 0.272, 95 % CI 0.165-0.449], length of hospital stay (RoM 0.695, 0.615 0.774), and 30-day overall complication rate (RR 0.637, 0.483-0.838) in favour of robotic surgery. For robotic versus MIS, 58 studies (21 RCTs, 37 PROs) demonstrated reduced blood loss (RoM 0.853, 0.736-0.969) and transfusion rate (RR 0.621, 0.390-0.988) in favour of robotic surgery but similar length of hospital stay (RoM 0.982, 0.936-1.027) and 30-day overall complication rate (RR 0.988, 0.822-1.188). In both comparisons, robotic surgery prolonged operative time (OS: RoM 1.073, 1.022-1.124; MIS: RoM 1.135, 1.096-1.173). The benefits of robotic surgery lacked robustness on RCT-sensitivity analyses. However, many studies, including the relatively few available RCTs, suffered from high risk of bias and inadequate statistical power. CONCLUSIONS: Our results showed that robotic surgery contributed positively to some perioperative outcomes but longer operative times remained a shortcoming. Better quality evidence is needed to guide surgical decision making regarding the precise clinical targets of this innovation in the next generation of its use. PMID- 26895900 TI - A novel endoscopic fluorescent band ligation method for tumor localization. AB - BACKGROUND: Accurate tumor localization is essential for minimally invasive surgery. This study describes the development of a novel endoscopic fluorescent band ligation method for the rapid and accurate identification of tumor sites during surgery. METHODS AND MATERIALS: The method utilized a fluorescent rubber band, made of indocyanine green (ICG) and a liquid rubber solution mixture, as well as a near-infrared fluorescence laparoscopic system with a dual light source using a high-powered light-emitting diode (LED) and a 785-nm laser diode. The fluorescent rubber bands were endoscopically placed on the mucosae of porcine stomachs and colons. During subsequent conventional laparoscopic stomach and colon surgery, the fluorescent bands were assayed using the near-infrared fluorescence laparoscopy system. RESULTS: The locations of the fluorescent clips were clearly identified on the fluorescence images in real time. The system was able to distinguish the two or three bands marked on the mucosal surfaces of the stomach and colon. Resection margins around the fluorescent bands were sufficient in the resected specimens obtained during stomach and colon surgery. CONCLUSION: These novel endoscopic fluorescent bands could be rapidly and accurately localized during stomach and colon surgery. Use of these bands may make possible the excision of exact target sites during minimally invasive gastrointestinal surgery. PMID- 26895899 TI - Endoscopic submucosal dissection for anorectal tumor with hemorrhoids close to the dentate line: a multicenter study of Hiroshima GI Endoscopy Study Group. AB - BACKGROUND: The lower rectum close to the dentate line has distinct characteristics, making endoscopic submucosal dissection (ESD) of tumors challenging. We assessed clinical outcomes of ESD for such patients with hemorrhoids. METHODS: Sixty-four patients (mean age, 68 years) underwent ESD for anorectal tumors close to the dentate line. We divided patients into those with (Group A, 45 patients) and without hemorrhoids (Group B, 19 patients). We examined en bloc and histological en bloc resection rates, procedure time, complication rates, and postoperative prognosis after ESD. RESULTS: The mean tumor size was 43 mm. Histologic diagnoses were adenoma (42 %, 27/64), carcinoma in situ (44 %, 28/64), and T1 carcinoma (14 %, 9/64). There was no significant difference in en bloc resection (93 %, 42/45 vs. 95 %, 18/19) or postoperative bleeding rates (16 %, 7/45 vs. 11 %, 2/19) between Groups A and B, respectively. The mean procedural durations were 120 and 124 min, respectively, in Groups A and B. No perforations occurred. There was no significant difference in postoperative anal pain rate between Groups A (18 %, 8/45) and B (16 %, 3/19), and it resolved within a few days in all cases. There was one case of stricture in Group B. Two patients with T1 carcinoma underwent additional surgery, one underwent chemotherapy, and five had no additional treatment. No recurrence occurred during the follow-up period of 38 months. CONCLUSIONS: ESD is safe and effective for anorectal tumors close to the dentate line in patients with hemorrhoids. PMID- 26895901 TI - Single-incision laparoscopic cholecystectomy: does it work? A systematic review. AB - BACKGROUND: Single-incision laparoscopic cholecystectomy (SILC) has been widely introduced into the clinical practice, but the real clinical benefits for patients still remain a matter of debate. We conducted a systematic review, according to the PRISMA guidelines comparing clinical and peri-operative outcomes of SILC and conventional laparoscopic cholecystectomy (CLC). METHOD: A literature search, including only randomised controlled trials (RCTs), was performed via PubMed, Google Scholar, Cochrane Library and Embase database. The reviewers extracted data from the manuscripts of selected articles including patient demographics, operative time, morbidity rate, post-operative length of stay, conversion rate, cost data, pain and satisfaction with cosmetic results. RESULT: Seventeen RCTs matching the inclusion criteria were finally selected for the analysis. A total of 1293 patients were involved in the review, including 663 (51.3 %) patients who have undergone SILC and 630 (48.7 %) patients who have undergone CLC. Post-operative pain was significantly worse in SILC patients in four studies, in CLC patients in four studies, while in the remnants seven studies, no differences in pain scores were found. Data on satisfaction for post operative cosmetics were significantly better for SILC patients in all studies but two. Operating time was significantly longer in SILC group while there is no statistically significant difference in conversion rate. Morbidity rate was similar in both groups, as was the incidence of bile duct injuries. Costs were significantly higher in SILC group. SILC was considered a more challenging procedure in all studies. CONCLUSION: The role of SILC is still controversial. Until now, no real significant benefit has been proven: overall satisfaction is the only clear advantage of SILC, and this is mainly related to cosmetic results. Indications to SILC are mainly limited to patients with uncomplicated disease, with BMI <= 30 kg/m(2), whose surgery is unlikely to be converted to an open or multiport approach. PMID- 26895902 TI - Incisional hernia after single-incision laparoscopic cholecystectomy: incidence and predictive factors. AB - AIM: To access the incidence and predictive factors of incisional hernia after single-incision laparoscopic cholecystectomy (SILC). METHODS: Eighty-two consecutive patients operated on for uncomplicated cholelithiasis between 2009 and 2013 were eligible for the study. Clinical outcome was assessed by a combination of case notes review, office consultation and telephone interview. Long-term incisional hernia rate was the major outcome of the study. Secondary outcome was the evaluation of predictive factors. Univariate and multivariate statistical analyses were performed using the following variables: age, gender, ASA score, BMI, risk, or comorbidity factors and surgical site infection. RESULTS: Six patients (7 %) were lost to follow-up after the 1-month office visit and excluded. The study group consisted of 16 men and 60 women with a median age of 42 years (range 18-69) and a BMI of 25 (range 19-34). Eight patients had risk or comorbidity factors, 46 were classified ASA I, and 30 ASA II. Early postoperative course was uneventful in all cases but two patients developed a superficial wound abscess after hospital discharge. With a median follow-up of 44 months (range 12-72), incisional hernia was noted in six patients (7.9 %). Multivariate logistic analysis revealed that age (OR 1.08, 95 % CI 1.00-1.16, p < 0.038) and BMI (OR 1.37, 95 % CI 1.03-1.82, p < 0.029) were independent predictive factors of developing an incisional hernia. The incidence of hernia was, respectively, 15 % in patients with an age >= 50 and 33 % in patients with a BMI >= 30. CONCLUSION: After SILC, we noted an incisional hernia rate of 8 %. To decrease the risk of developing that specific complication, SILC should only be proposed to young and non-obese patients. PMID- 26895903 TI - Review of 1000 fibrin glue mesh fixation during endoscopic totally extraperitoneal (TEP) inguinal hernia repair. AB - BACKGROUND: Chronic pain is a common complication arising after conventional open herniorrhaphy and to a lesser extent postlaparoscopic inguinal hernia repairs as groin incision is avoided. Although published studies support elimination of mesh fixation during endoscopic procedures, the vast majority of surgeons will still recommend it by fear of encountering increased recurrence rates, if omitted. Regrettably, penetrating staple or tack fixation devices are the preferred methods to secure the mesh and cannot be applied at the level of the triangles of 'doom' and 'pain' where hernia tends to reoccur the most. This ongoing prospective cohort study aimed to confirm the safety and advantages of fibrin glue, as a substitute to staple mesh fixation during totally extraperitoneal (TEP) inguinal hernia repair. METHODS: Over a 10-year period, 703 patients underwent 1000 elective TEP inguinal hernia repairs. Mesh fixation was achieved using exclusively fibrin sealant. Patients were reviewed at 2, 6 weeks and thereafter on an ad hoc basis if judged necessary until complete resolution of their symptoms. Quality of life (QoL) was assessed in a subgroup of 320 patients using the Carolina Comfort Scale (CCS). RESULTS: No conversion to open surgery was observed. There were three cases of major morbidities and no mortality. Three months after surgery, only seven patients (1 %) experienced chronic groin or testicular discomfort and none of them required prescription painkillers. When using the CCS, at 2 weeks 93.1 % of the patients were either satisfied or very satisfied with their outcome. This satisfaction index increased up to 99.2 % at 6 weeks post surgery. Finally, only eight hernia recurrences (1.1 %) were reported, of which five occurred during the first month of the study. CONCLUSION: Fibrin glue mesh fixation of inguinal hernia during TEP repair is extremely safe and reliable, with a very high satisfaction index for the patients and limited risk of developing chronic pain. PMID- 26895904 TI - Cell-coating affects tissue integration of synthetic and biologic meshes: comparative analysis of the onlay and underlay mesh positioning in rats. AB - BACKGROUND: While mesh reinforcement is recognized as the optimal strategy for many hernia repairs, there remains debate on the optimal position for deployment and characteristics that lead to improved biocompatibility. Coatings are an avenue by which integration may be improved. Our aim was to evaluate tissue integration between uncoated, fibroblast- and mesenchymal stem cell-coated meshes placed as subcutaneous onlay (ON) or intraperitoneal underlay (UN). METHODS: Three commonly used biologic and synthetic hernia meshes were tested including Parietex, TIGR and Strattice. Each mesh was coated with rat kidney fibroblasts (NRKs) or rat mesenchymal stem cells (MSCs) along with an uncoated group. In the ON group, mesh was fixated on top of the external oblique fascia. In the UN group, mesh was placed against the intact peritoneum. Animals were survived for 30 days and killed for biomechanical and histologic analysis. A "T"-peel test was performed on a mesh-tissue explant from each sample to analyze the strength of integration at the mesh-tissue interface. Tissue integration was evaluated histologically using an established scoring system. RESULTS: All uncoated meshes demonstrated significantly higher tissue ingrowth in the UN compared to ON position. Cell-coating of synthetic meshes decreased tissue ingrowth as UN, but increased it as ON, with a net effect of minimizing biomechanical difference between the two positions. In the biologic group however, NRK-coating decreased tissue ingrowth regardless of position, while MSC-coating increased it in both ON and UN positions. CONCLUSIONS: Both cell-coating and positioning affect mesh tissue integration. Integration is superior in the underlay position compared to onlay when uncoated. Cell-coating of selected synthetic meshes can improve integration, particularly in the onlay position. Furthermore, MSCs appear to be a viable choice for biologic mesh coating, especially when implanted as an onlay. Overall, cell-coating of surgical meshes appears to a have a potential to improve mesh-tissue integration. PMID- 26895905 TI - Laparoscopic left pancreatectomy: early results after 115 consecutive patients. AB - INTRODUCTION: Despite its proven feasibility and good results, the use of laparoscopy in left-sided pancreatic lesions is considered a challenging procedure, and therefore, its utilization is still low. In this paper, we aim to describe the early outcomes obtained after laparoscopic left pancreatectomies performed over 15 years. PATIENTS AND METHODS: From 1997 until 2014, 115 consecutive patients underwent laparoscopic left pancreatectomy at CHU Bordeaux and Centre Hepato-Biliaire, which were prospectively recorded in a database. An analysis of this database was performed in order to evaluate preoperative, intraoperative and immediate postoperative outcomes. RESULTS: Laparoscopic left pancreatectomy with spleen conservation was performed in 64 patients (55.7 %). The median operative time was 220 min, and median blood loss was 200 ml. Conversion to open surgery was made in 15 (13 %) patients. Median postoperative hospital stay was 11 days, and overall postoperative complications occurred in 59 patients (51.3 %). Of these, 25.4 % were Clavien-Dindo grade III and above. The rate of clinical PF was 11.3 %. Three of the 64 patients with splenic preservation (4.7 %) developed a splenic infarction, and one of them needed splenectomy. CONCLUSIONS: Results obtained after a long series of laparoscopic left pancreatectomy confirm its favorable outcomes and its association with a low postoperative morbidity rate. PMID- 26895906 TI - Laparoscopic hepatectomy in cirrhotics: safe if you adjust technique. AB - BACKGROUND: Minimally invasive liver surgery is a growing field, and a small number of recent reports have suggested that laparoscopic liver resection (LLR) is feasible even in patients with cirrhosis. However, parenchymal transection of the cirrhotic liver is challenging due to fibrosis and portal hypertension. There is a paucity of data regarding the technical modifications necessary to safely transect the diseased parenchyma. METHODS: Patients undergoing LLR by a single surgeon between 2008 and 2015 were reviewed. Patients with cirrhosis were compared to those without cirrhosis to examine differences in surgical technique, intraoperative characteristics, and outcomes (including liver-related morbidity and general postoperative complication rates). RESULTS: A total of 167 patients underwent LLR during the study period. Forty-eight (29 %) had cirrhosis, of which 43 (90 %) had hepatitis C. Most had Child-Pugh class A disease (85 %). Compared to noncirrhotics, patients with cirrhosis were older, had more comorbidities, and were more likely to have hepatocellular carcinoma. Precoagulation before parenchymal transection was used more frequently in cirrhotics (65 vs. 15 %, P < 0.001), and mean portal triad clamping time was longer (32 vs. 22 min, P = 0.002). There were few conversions to open surgery, though hand-assisted laparoscopy was used as an alternative to converting to open in three patients with cirrhosis. Blood loss was relatively low for both groups. Although there were more postoperative complications among cirrhotics (38 vs. 13 %, P = 0.001), this was almost entirely due to a higher rate of minor (Clavien-Dindo I or II) complications. Liver-related morbidity, major complications, and mortality rates were similar. CONCLUSIONS: LLR is safe for selected patients with cirrhosis. The added complexity associated with the division of diseased liver parenchyma may be overcome with some form of technique modification, including more liberal use of precoagulation, portal triad clamping, or a hand-assist port. PMID- 26895908 TI - Incisional hernias after open versus laparoscopic surgery for colonic cancer: a nationwide cohort study. AB - BACKGROUND: Laparoscopic surgery for colonic cancer decreases the incidence of postoperative complications and length of hospital stay as compared with open surgery, while the oncologic outcome remains equivalent. It is unknown whether the surgical approach impacts on the long-term rate of incisional hernia. Furthermore, risk factors for incisional hernia formation are not fully elucidated. The aim of this study was to evaluate the long-term effect of elective open versus laparoscopic surgery for colonic cancer on development of incisional hernia. METHODS: This nationwide cohort study included patients operated on electively for colonic cancer with primary anastomosis in Denmark from 2001 to 2008. Patient data were obtained from the database of the Danish Colorectal Cancer Group and merged with data from the National Patient Registry. Multivariable Cox regression and competing risks analysis were performed. RESULTS: A total of 8489 patients were included, with a median follow-up of 8.8 (interquartile range 7.0-10.7) years. The incidence of incisional hernia was increased among patients operated on with open techniques compared with patients undergoing laparoscopic surgery (7.3 vs. 5.2 %, p < 0.001). After adjustment for confounders, laparoscopic approach was associated with a decreased risk of incisional hernia formation (hazard ratio [HR] 0.62, 95 % confidence interval [CI] 0.44-0.89; p = 0.009). Other factors associated with increased risk of incisional hernia were wound infection, fascial dehiscence, anastomotic leak, and body mass index >25 kg/m(2). CONCLUSIONS: This nationwide analysis demonstrated that laparoscopic as compared with open access for curative resection of colonic cancer was associated with a decreased risk of incisional hernia formation. PMID- 26895909 TI - Diagnostic accuracy of staging laparoscopy for detecting metastasized or locally advanced perihilar cholangiocarcinoma: a systematic review and meta-analysis. AB - BACKGROUND: Despite extensive preoperative staging, still almost half of patients with potentially resectable perihilar cholangiocarcinoma (PHC) have locally advanced or metastasized disease upon exploratory laparotomy. The value of routine staging laparoscopy (SL) in these patients remains unclear with varying results reported in the literature. The aim of the present systematic review was to provide an overview of studies on SL in PHC and to define its current role in preoperative staging. METHODS: A systematic review and meta-analysis were performed in PubMed and EMBASE regarding studies providing data on the diagnostic accuracy of SL in PHC. Primary outcome measures were the overall yield and sensitivity to detect unresectable disease. Secondary outcomes were the yield and sensitivity for recent studies (after 2010) and large study cohorts (>=100 patients) and specific (metastatic) lesions. Methodological quality of studies was assessed with the Quality Assessment of Diagnostic Accuracy Studies tool. RESULTS: From 173 records, 12 studies including 832 patients met the inclusion criteria. The yield of SL in PHC varied from 6.4 to 45.0 % with a pooled yield of 24.4 % [95 % confidence interval (CI) 16.4-33.4]. Sensitivity to detect unresectable disease ranged from 31.6 to 75 % with a pooled sensitivity of 52.2 % (95 % CI 47.1-57.2). Sensitivity was highest for peritoneal metastases (80.7 %, 95 % CI 70.9-88.3). Subgroup analysis revealed that the yield and sensitivity tended to be lower for studies after 2010. Considerable heterogeneity was detected among the studies. CONCLUSIONS: The results of the pooled analyses suggest that one in four patients with potentially resectable PHC benefits from SL. Given considerable heterogeneity, a trend to lower yield in more recent studies and further improvement of preoperative imaging over time, the routine use of SL seems discouraging. Studies that identify predictors of unresectability, that enable selection of patients who will benefit the most from this procedure, are needed. PMID- 26895910 TI - Total laparoscopic living donor right hemihepatectomy: first case in China mainland and literature review. AB - BACKGROUND: Total laparoscopic living donor right hemihepatectomy (LDRH) has been performed in several experienced transplant center [1-4]. We here report the first case of LDRH in China mainland and literature review. METHODS: A 47-year old man volunteered for living donation to his wife who suffered sclerosing cholangitis-related liver cirrhosis and hepatocellular carcinoma. RESULTS: Donor height is 165 cm and weight is 65 kg, while the BMI is 23.9. Preoperative liver function tests were normal. The CT volume evaluation showed that the graft to body weight ratio (GBWR) was 1.42 % and the remnant liver volume was 36.3 % for right graft without middle hepatic vein. Biopsy result showed minimal steatosis. The anatomy of hepatic vein, artery, portal vein and bile duct was normal. A transection was performed along the cut line which was to the right side of middle hepatic vein. Two branches of the middle hepatic vein (Segment V and Segment VIII) were <5 mm in diameter, with no need of reconstruction. Hilar dissection was meticulously performed. Right portal vein, hepatic artery and bile duct were transected above the bifurcation. The right liver graft was placed in a retrieval bag and removed from suprapubic incision. The real graft volume was 660 ml with a revised GBWR of 1.14 %. Warm ischemia time was about 4 min. The postoperative course was uneventful for the donor. Literature review is shown in Table 1. CONCLUSION: Total LDRH has been demonstrated technically feasible in selected adult donors. It may be a safe and minimally invasive option for adult donors in experienced transplant center. PMID- 26895907 TI - Comparison of minilaparoscopy and single-incision intragastric surgery for gastric submucosal tumor resection in a porcine model. AB - BACKGROUND: The aim of this study was to develop an easy-to-induce and reproducible model of gastric submucosal tumor in swine to compare minilaparoscopy (ML) with single-incision (SI) intragastric surgery. METHODS: Twelve healthy female pigs (weight 30.94 +/- 2.49 kg) underwent a transparietal injection of sterile alginate at the level of Z-line (n = 6) and at the pre pyloric area (n = 6) creating a model of gastric submucosal pseudotumor. The operative procedures included intragastric resection with ML and SI approaches of cardiac and pre-pyloric lesions, with gastroscopic assistance. After resection, the gastric mucosal layer was closed using intracorporeal sutures. The operative time, complication rate and clinical evolution after 1 month were compared in the four groups that the pigs were arranged. RESULTS: The pseudotumors ranged in size from 3 to 6 cm in diameter. The access of the gastric cavity and resection of the experimental SMP and suturing of the mucosa were performed successfully in 12 animals using both approaches. Mean time to perform the exeresis of gastric cardia tumors was significantly higher in single-incision approach. No significant differences were observed in the surgical time during pyloric surgery. Minilaparoscopic approach reduced significantly the mucosa closure time in esophagogastric and pyloric pseudotumors. One month after, no alterations were shown in the abdominal cavity using exploratory laparotomy. CONCLUSIONS: The technical feasibility of performing safe and efficient intragastric approach of submucosal pseudotumors in swine model was verified in this study. Intragastric ML has advantages over SI, namely regarding the reduction in total surgical times and the fewer technical difficulties. PMID- 26895911 TI - Minimally invasive entero-enteral dual-path bypass using self-assembling magnets. AB - BACKGROUND: A minimally invasive method of entero-enteral bypass may be desirable for treatment of obstruction, obesity, or metabolic syndrome. We have developed a technology based on miniature self-assembling magnets which create large-caliber anastomoses (incisionless anastomosis system or IAS). The aim of this study was to assess (a) procedural characteristics of IAS deployment and (b) long-term integrity and patency of the resulting jejuno-ileal dual-path bypass. METHODS: Endoscopic jejuno-ileal bypass creation using IAS magnets was performed in 8 Yorkshire pigs survived 3 months. PROCEDURE: The jejunal magnet was endoscopically deployed. However, the ileal magnet required surgical delivery given restraints of porcine anatomy. A 5-mm enterotomy was created through which the ileal magnet was inserted using a modified laparoscopic delivery tool. Magnets were manually coupled. Pigs underwent serial endoscopies for anastomosis assessment. Three-month necropsies were performed, followed by pressure testing of anastomoses and histological analysis. RESULTS: Jejuno-ileal bypass creation using self-assembling IAS magnets was successful in all 8 pigs (100 %). Patent, leak-free bypasses formed in all animals by day 10. All IAS magnets were expelled by day 12. Anastomoses were widely patent at 3 months, with mean maximal diameter of 30 mm. At necropsy, adhesions were minimal. Pressure testing confirmed superior integrity of anastomotic tissue. Histology showed full epithelialization across the anastomosis with no evidence of submucosal fibrosis or inflammation. CONCLUSIONS: Entero-enteral bypass using self-assembling IAS magnets is safe and technically feasible in the porcine model. IAS magnets can be rapidly delivered endoscopically or through a modified laparoscopic device. Expulsion of fused magnets avoids retention of prosthetic material. Anastomoses are widely patent and fully re-epithelialized. Three-month pressure testing reveals anastomotic tissue to be as robust as native tissue, while necropsy and histology suggests minimal/absent tissue inflammation. In human anatomy, a fully endoscopic jejuno ileal bypass using IAS magnets may be feasible. PMID- 26895912 TI - Long-term results of endoscopic balloon dilation for treatment of colorectal anastomotic stenosis. AB - BACKGROUND: Despite standardized techniques, anastomotic complications after colorectal resection remain a challenging problem. Among those, anastomotic stricture is a debilitating outcome which often requires multiple interventions and which is prone to recur. The present series investigates the long-term results of endoscopic balloon dilation for stenotic colorectal anastomosis. METHODS: Consecutive patients from a single institution who presented with an anastomotic stenosis after a colorectal resection were identified using a prospective clinical database. Medical records were systematically reviewed to detail patients' outcomes. RESULTS: Over 17 years (1988-2015), 2361 consecutive patients underwent a colorectal anastomosis. Of those, 76 patients (3.2 %) suffered a symptomatic anastomotic stenosis within a median of 5 months (interquartile range (IQR) 2-13) of the index procedure. All stenoses were primarily treated by endoscopic balloon dilation. Median follow-up was 11 years (IQR 7-14). In half the patients, one to two attempts at endoscopic balloon dilation definitively relieved the stenosis. Overall, the median number of endoscopic balloon dilation required was 3 (IQR 2-3). Recurrence rates at 1 year, 3 year, and 5 year were 11, 22, and 25 %, respectively. Median time to recurrence was 12 months (IQR 3-24). Ultimately, two patients (2.6 %) underwent an operation due to failure of endoscopic treatment. All other patients (97.4 %) were treated successfully with endoscopic balloon dilation. A total of 12 patients (15.7 %) suffered a complication from endoscopic dilation. Of those, 11 were minor bleeding and one was a perforation at the level of the anastomosis. All complications were managed conservatively, and no emergency procedure was required as a consequence of attempted endoscopic balloon dilation. CONCLUSION: Endoscopic balloon dilation is a safe approach to effectively relieve an anastomotic stenosis following a colorectal resection. PMID- 26895913 TI - Collaborative performance in laparoscopic teams: behavioral evidences from simulation. AB - OBJECTIVES: To examine the frequency of movement de-synchronization between a surgeon and assistant in a laparoscopic simulation task, and test whether it can be a valid behavior marker for team performance. METHODS: Fourteen subjects formed a total of 22 dyad teams. Each team performed a laparoscopic task where the camera driver navigated a laparoscope for the operator to transport a plastic cylinder between targets. Key movement landmarks were annotated from recorded surgical videos and were used to identify team behaviors and performance. Task completion time, number of movement de-synchronization, and errors (cylinder drops) were compared over 3 performance groups (elite, intermediate, poor) and 2 types of movements (on-site manipulation vs. position-shifting. RESULTS: Task completion time of elite teams was shorter than intermediate and poor teams (33.3 vs. 66.8 vs. 141.2 s, P < 0.001). Elite teams made fewer errors (0.1 vs. 0.5 vs. 0.9, P = 0.063) and recorded fewer numbers of de-synchronization than poor teams (2.9 vs. 3.0 vs. 4.9, P = 0.009). We also found that the on-site manipulation took longer task time (113.5 vs. 51.2 s, P < 0.001) and recorded fewer de synchronization (0.6 vs. 5.3, P < 0.001) than position-shifting tasks. However, there is no significance in the measure of errors (P = 0.029). Interaction effects were revealed between performance groups and two movement types in task time (P = 0.010) and movement de-synchronization (P = 0.003). CONCLUSIONS: Video analysis is a useful tool for identifying team behaviors during surgery. Movement de-synchronization between surgeons and assistant reveals team cooperation in laparoscopic procedure. The evidence where de-synchronization occurred frequently during the position-shifting tasks rather than during the on-site manipulation suggests team collaborative behaviors can be affected by different task requirements. PMID- 26895914 TI - Laparoscopic splenectomy is a better surgical approach for spleen-relevant disorders: a comprehensive meta-analysis based on 15-year literatures. AB - BACKGROUND: Currently, whether laparoscopic or open splenectomy is a gold standard option for spleen abnormalities remains in controversy. There is in deficiency of academic evidence concerning the surgical efficacy and safety of both comparative managements. In order to surgically appraise the applied potentials of both approaches, we hence performed this comprehensive meta analysis on the basis of 15-year literatures. METHODS: Via searching of PubMed, EMBASE, Web of Science, and Cochrane Library databases, overall 37 original articles were eligibly incorporated into our meta-analysis and subdivided into six sections. In accordance with the Cochrane Collaboration protocol, all statistical procedures were mathematically conducted in a standard manner. Publication bias was additionally evaluated by funnel plot and Egger's test. RESULTS: Irrespective of the diversified splenic disorders, laparoscopic splenectomy was superior to open technique owing to its fewer estimated blood loss, shorter postoperative hospital stay as well as lower complication rate (P < 0.05). As for operative duration and perioperative mortality, a statistical similarity was observed amid both surgical measures (P > 0.05). CONCLUSION: Technically, laparoscopic splenectomy should be recommended as a prior remedy with its advantage of rapid recovery and minimally physical damage, in addition to its comparably surgical efficacy against that of open manipulation. PMID- 26895915 TI - An assessment of existing risk stratification guidelines for the evaluation of patients with suspected choledocholithiasis. AB - BACKGROUND: Prior studies have demonstrated that existing risk stratification guidelines for the evaluation of suspected choledocholithiasis lack accuracy, leading to the overutilization of endoscopic retrograde cholangiopancreatography (ERCP). The aim of our study was to evaluate the performance characteristics of published guidelines in predicting choledocholithiasis and to determine the impact of laboratory trends on diagnostic accuracy. METHODS: We identified patients with suspected choledocholithiasis hospitalized over a 5-year period (2009-2014) at a tertiary care academic medical center. Among eligible patients, we assessed the performance characteristics of the American Society for Gastrointestinal Endoscopy (ASGE) guidelines predicting the presence of choledocholithiasis, confirmed by endoscopic ultrasound, magnetic resonance cholangiography, ERCP, or intra-operative cholangiography. We also evaluated whether a second set of liver function tests improved the accuracy of the guidelines. RESULTS: On presentation, 71 of the 173 eligible patients (41.4 %) met ASGE high-probability criteria for choledocholithiasis. Of these, only 39 (54.9 %) were found to have a choledocholithiasis on confirmatory testing. Conversely, of the 102 patients (58.6 %) who were classified as low or intermediate probability, 32 (31.4 %) had choledocholithiasis. Overall, the accuracy of the guidelines was 63 % (sensitivity 54.9 %; specificity 68.6 %). Incorporating a second set of laboratory tests did not improve accuracy (62.7 %), and a significant decline in liver function tests did not reliably predict spontaneous stone passage. CONCLUSIONS: Existing guidelines performed suboptimally for predicting choledocholithiasis in our patient population, similar to other validation studies. These findings further underscore the importance of developing alternate risk stratification tools for choledocholithiasis, aiming to minimize unnecessary diagnostic ERCP. PMID- 26895916 TI - Electrophysiology-based quality assurance of nerve-sparing in laparoscopic rectal cancer surgery: Is it worth the effort? AB - BACKGROUND: After low anterior resection for rectal cancer, visual assessment of pelvic autonomic nerve preservation can be difficult due to the complexity of neuroanatomy, as well as surgery- and patient-related factors. The present study aimed to evaluate nerve-sparing quality assurance using the laparoscopic neuromapping (LNM) technique. METHODS: We prospectively investigated a series of 30 patients undergoing laparoscopic low anterior resection. Nerve-sparing was evaluated both visually and electrophysiologically. LNM was performed using stimulation of pelvic autonomic nerves under simultaneous cystomanometry and processed electromyography of the internal anal sphincter. Urogenital and anorectal functions were evaluated using validated and standardized questionnaires preoperatively, at short-term follow-up, and at mid-term follow-up at a median of 9 months (range 6-12 months) after surgery. RESULTS: One patient reported new onset of urinary dysfunction, and another patient reported new onset of anorectal dysfunction. Of the 20 sexually active patients, five reported sexual dysfunction. Visual assessment by laparoscopy confirmed complete nerve preservation in 28 of 30 cases. For prediction of urinary and anorectal function, LNM sensitivity, specificity, positive and negative predictive value, and overall accuracy were each 100 %. LNM with combined assessment for prediction of sexual function yielded a sensitivity of 80 %, specificity of 93 %, positive predictive value of 80 %, negative predictive value of 93 %, and overall accuracy of 90 %. CONCLUSIONS: LNM is an appropriate method for reliable quality assurance of laparoscopic nerve-sparing. PMID- 26895917 TI - Vaginal morcellation through the posterior cul-de-sac using an electromechanical morcellator after laparoscopic myomectomy or subtotal hysterectomy: a retrospective, case-control study. AB - BACKGROUND: This study aimed to evaluate the feasibility and safety of vaginal morcellation (VM) through the posterior cul-de-sac (PCDS) using an electromechanical morcellator and to compare the perioperative outcomes of VM with those of abdominal morcellation (AM) to remove a single myoma. METHODS: The characteristics of 245 consecutive patients who had undergone VM after laparoscopic myomectomy or subtotal hysterectomy were summarized. A retrospective, matched, case-control study was performed; 64 patients had a myoma weighting 100 g or more. Cases were matched with controls (ratio 1:2), who had undergone AM, by age, body mass index, specimen weight, surgical type, and surgeon. Body image questionnaires were used to assess the cosmetic outcome. Medians were analyzed using the Mann-Whitney U test. Differences between means were assessed using Student's t test. Dichotomous groupings were analyzed using either the Chi-squared test or Fisher's exact test, as appropriate. RESULTS: All 245 patients underwent VM without complications. The mean weight of the specimens was 197.2 g (range 78.5-1477 g), and the mean duration of morcellation was 13.0 min (range 2.0-45.0 min). Two hours after surgery, the visual analog scale (VAS) score was significantly lower in the VM group than in the AM group (P = 0.03). Moreover, the morcellator used was significantly larger in the VM group (P < 0.001), and morcellation duration was significantly shorter in the VM group (P < 0.001). Finally, cosmetic outcome was significantly better in the VM group (P < 0.02). The two groups did not differ significantly in terms of hospitalization duration, surgery duration or VAS score 24 and 47 h postoperatively. CONCLUSION: VM through the PCDS using an electromechanical morcellator is a safe and feasible technique for surgical excision. The benefits of the procedure over AM are reduced immediate postoperative pain, shorter morcellation time, and better cosmesis. PMID- 26895918 TI - Linear-shaped gastroduodenostomy (LSGD): safe and feasible technique of intracorporeal Billroth I anastomosis. AB - BACKGROUND: Although delta-shaped gastroduodenostomy (DSGD) is used increasingly as an intracorporeal Billroth I anastomosis after distal gastrectomy, worries about anatomical distortion always exist in twisting stomach and making an oblique incision on duodenum. We developed a new method of intracorporeal gastroduodenostomy, the linear-shaped gastroduodenostomy (LSGD), in which anastomosis is done using endoscopic linear staplers only without any complicated rotation. In this report, we introduced LSGD and compared its short-term and long term outcomes with DSGD. METHODS: We analyzed 261 consecutive gastric cancer patients who underwent the intracorporeal gastroduodenostomy between January 2009 and May 2014 (LSGD: 190, DSGD: 71), retrospectively. All of them underwent a laparoscopic or robotic distal gastrectomy with regional lymph node dissection. Early surgical outcomes such as operation time, postoperative complications, days until soft diet began, length of hospital stay, and endoscopic findings in postoperative 6 and 12 months were evaluated. RESULTS: Although the proportion of robotic approach and D2 lymphadenectomy were significantly higher in LSGD group, the rates for overall complications (13.2 % [LSGD] vs. 9.9 % [DSGD], p = 0.470) and major complications (5.8 vs. 5.6 %, p = 1.0) were similar between two groups. There were no differences in anastomotic bleeding (1.1 vs. 1.4 %, p = 1.0), stenosis (3.2 vs. 2.8 %, p = 1.0), and leakage (0.5 vs. 0.0 %, p = 1.0). Endoscopy performed 6 months postoperatively showed that residual food (p = 0.022), gastritis (p = 0.018), and bile reflux (42.0 vs. 63.2 %, p = 0.003) were significantly decreased in LSGD and there were no significant differences in postoperative 12 months. CONCLUSION: LSGD is an innovative reconstruction technique with comparable short-term outcomes to DSGD. In addition, reduced residual food, gastritis, and bile reflux were seen in LSGD. PMID- 26895919 TI - Evaluating the effect of distractions in the operating room on clinical decision making and patient safety. AB - BACKGROUND: Answering telephone calls and pagers is common distraction in the operating room. We sought to evaluate the impact of distractions on patient care by (1) assessing the accuracy and safety of responses to clinical questions posed to a surgeon while operating and (2) determining whether pager distractions affect simulation-based surgical performance. METHODS: We conducted a randomized crossover study of obstetrics and gynecology residents. After studying a patient sign-out list, subjects performed a virtual salpingectomy. They were randomized to a distraction phase followed by quiet phase or vice versa. In the distraction phase, a pager beeped and subjects were asked questions based on the sign-out list. Accuracy of responses and the number of unsafe responses were recorded. In the quiet phase, trainees performed the task uninterrupted. Measures of surgical performance were successful task completion, time to task completion and operative blood loss. RESULTS: The mean score for correct responses to clinical questions during the distracted phase was 80 % (SD +/-14 %). Nineteen residents (63 %) made at least 1 unsafe clinical decision while operating on the simulator (range 0-3). Subjects were more likely to successfully complete the surgical task in the allotted time under the quiet compared to distraction condition (OR 11.3, p = 0.03). There was no difference between the conditions in paired analysis for mean time (seconds) to task completion [426 (SD 133) vs. 440 (SD 186), p = 0.61] and mean operative blood loss (mL) [73.14 (SD 106) vs. 112.70 (SD 358), p = 0.47]. CONCLUSIONS: Distractions in the operating room may have a profound impact on patient safety on the wards. While multitasking in a simulated setting, the majority of residents made at least one unsafe clinical decision. Pager distractions also hindered surgical residents' ability to complete a simulated laparoscopic task in the allotted time without affecting other variables of surgical performance. PMID- 26895920 TI - Effects of intraoperative protective lung ventilation on postoperative pulmonary complications in patients with laparoscopic surgery: prospective, randomized and controlled trial. AB - BACKGROUND: Respiratory functions are usually impaired during pneumoperitoneum for laparoscopic surgery. This randomized, controlled and single-blinded study was performed to evaluate whether intraoperative protective lung ventilation influences postoperative pulmonary complications after laparoscopic hepatobiliary surgery. METHODS: Sixty-two patients were randomized to receive either conventional ventilation with alveolar recruitment maneuver (tidal volume of 10 ml/kg with inspiratory pressure of 40 cmH2O for 30 s after the end of pneumoperitoneum, group R), or protective lung ventilation (low tidal volume of 6 ml/kg with positive end-expiratory pressure [PEEP] of 5 cmH2O, group P). Induction and maintenance of anesthesia were done with balanced anesthesia. Respiratory complications such as atelectasis, pneumonia or desaturation were observed postoperatively. The length of hospital stay, arterial blood gas analysis, peak inspiratory pressure and hemodynamic variables were also recorded. Results are presented as mean +/- SD or number of patients (%). RESULTS: Postoperative pulmonary complications (P = 0.023) and desaturation below 90 % (P = 0.016) occurred less frequently in group P than in group R. Eight patients of group R and 3 patients of group P showed atelectasis. Pneumonia was diagnosed in 1 patient of group R. No differences were observed in the length of hospital stay, arterial blood gas analysis (pH, PaO2, PaCO2 and PAO2) and hemodynamic variables except PAO2, AaDO2 and peak inspiratory pressure between the two groups. CONCLUSION: Protective lung ventilation (low tidal volume with PEEP) during pneumoperitoneum was associated with less incidences of pulmonary complications than conventional ventilation with alveolar recruitment maneuver after laparoscopic hepatobiliary surgery. PMID- 26895921 TI - Oncologic outcomes of robotic thyroidectomy: 5-year experience with propensity score matching. AB - BACKGROUND: The oncologic outcome of robotic thyroidectomy is not yet well established. The aim of this study was to evaluate the recurrence rate after robotic thyroidectomy in comparison with conventional thyroidectomy for papillary thyroid carcinoma (PTC). METHODS: We analyzed 896 patients with PTC who either underwent robotic (212 patients using a gasless unilateral axillary or an axillo breast approach) or conventional cervical thyroidectomy (684 patients) with/without central neck dissection between October 2008 and February 2014. We excluded patients who underwent concomitant lateral neck dissection or completion thyroidectomy, and cases with T4 tumor, tumor lager than 4 cm, other types of thyroid cancer, recurrent cancer, and distant metastasis. A propensity score matching analysis was done with ten covariates including age, gender, body mass index, tumor size, multifocality, bilaterality, extrathyroidal extension, type of thyroidectomy, extent of central neck dissection, and RAI ablation to reduce selection bias. RESULTS: In baseline data, the male ratio and the mean age were lower in the robotic group. Stage, multifocality, and bilaterality were higher in the conventional group. The rate of total thyroidectomy was higher in the conventional group. The two matched groups of each 185 patients were produced and well balanced by propensity score matching. In the comparison of propensity score matched groups, operative time was longer in the robotic group (P < 0.001), and postoperative complications did not differ between the two groups, except for transient hypoparathyroidism and formation of seroma. The recurrence rate did not differ between the two groups after a mean follow-up of 43.6 months (0.5 and 1.1 % in the robotic and conventional groups, respectively, P = 0.375). CONCLUSION: The oncologic outcome of robotic thyroidectomy in 5-year experience is comparable to that of conventional thyroidectomy in selected patients with PTC. PMID- 26895923 TI - Economic impact of clinical variability in preoperative testing for major outpatient surgery. AB - BACKGROUND: With the purpose of decreasing the existing variability in the criteria of preoperative evaluation and facilitating the clinical decision-making process, our hospital has a protocol of preoperative tests to use with ASA I and ASA II patients. The aim of the study was to calculate the economic impact caused by clinicians' non-adherence to the protocol for the anaesthesiological evaluation of ASA 1 and ASA II patients. METHODS: A retrospective study of costs with a random sample of 353 patients that were seen in the consultation for Anesthesiology over a period of one year. Aspects related to the costs, patient's profiles and specialties were analysed, according to the degree of fulfillment of the protocol. RESULTS: The lack of adherence to the the protocol was 70%. 130 chest X-rays and 218 ECG were performed without indication. This generated an excess costs of 34 ? per patient. Taking into account the expenses of both tests and the attended population undergoing ambulatory surgery during the one-year period, an excess spending for the hospital of between 69.164 ? and 83.312 ? was estimated. CONCLUSIONS: Clinical variability should be reduced and the creation of synergies between the different departments should be enhanced in order to adjust the request for unnecessary complementary tests to decrease health care and to improve the quality of patient care. PMID- 26895922 TI - Long-term outcomes of palliation for unresectable colorectal cancer obstruction in patients with good performance status: endoscopic stent versus surgery. AB - BACKGROUND: In patients with unresectable colorectal cancer (CRC) obstruction, choosing whether to perform self-expandable metal stent (SEMS) or palliative surgery is challenging, especially in those with good performance status. We aimed to compare the long-term outcomes of SEMS with those of palliative surgery in patients with unresectable CRC obstruction. METHODS: This retrospective study comprised 114 patients with unresectable CRC obstruction who underwent SEMS placement (n = 73) or palliative surgery (n = 41). The main outcome measurements were success rate, adverse events, patency, and survival duration. RESULTS: Early clinical success rates did not differ between SEMS and surgery. However, the rate of late adverse events was significantly higher in the SEMS group (27.4 vs. 9.8 %; P = .005). Patency duration was shorter after SEMS than after surgery (163 vs. 349 days; P < .001), even after additional intervention (202 vs. 349 days; P < .001). The median survival was significantly shorter after SEMS than after surgery (209 vs. 349 days; P = .005). Survival differed between treatments in patients with Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (P = .016) but not in those with ECOG 2 or 3 (P = .487), and this was confirmed by multivariate analysis, which showed that surgery was a significant favorable predictor of survival for patients with ECOG 0 or 1 (hazard ratio .442; 95 % confidence interval .234-.835; P = .016). CONCLUSIONS: Surgery may be preferable to SEMS for the palliation of unresectable CRC obstruction in patients with good performance status, especially ECOG 0 or 1. PMID- 26895924 TI - Treatment of complex perineal trauma. A review of the literature. AB - Perineal injuries are uncommon, but not rare. They may present a wide variety of injury patterns which demand an accurate diagnostic assessment and treatment. Perineal injuries may occur as isolated injuries to the soft tissues or may be associated with pelvic organ, abdominal or even lower extremity injury. Hence the importance to know in depth not only the anatomy of the perineum and its organs, but also the implications of the patient's hemodynamic stability on the decision making process when treating these injuries using established trauma guidelines. The purpose of this review is to describe the current epidemiology and clinical presentation of perineal injuries in order to provide specific guidelines for the diagnosis and treatment of both stable and unstable patients. PMID- 26895925 TI - An unusual presentation of a mucinous cystadenoma of the appendix. PMID- 26895926 TI - Response to the Letter to the Editor "Hemodynamics in the Microcirculation" by A. G. Koutsiaris. PMID- 26895927 TI - Hemodynamics in the Microcirculation. PMID- 26895928 TI - My First Restraint. PMID- 26895929 TI - Technology in Psychiatric Education: The Technology Innovation Column. PMID- 26895930 TI - Required and Elective Experiences During the 4th Year: An Analysis of ACGME Accredited Psychiatry Residency Program Websites. AB - OBJECTIVE: The objective of this study was to assess and describe required and elective components of the 4th post-graduate year (PGY4) in psychiatry residency programs. METHODS: We reviewed the websites of all 193 2014-2015 ACGME accredited psychiatry residency programs for content describing the specific components of the PGY4 year. RESULTS: Nearly all residency programs (99 %) had some form of required experiences during the PGY4 year. Ninety-four percent had clinical requirements for PGY4 residents, with longitudinal outpatient clinic being the most common (77 %). All programs offered some elective time during PGY4, but the amount of time ranged from 2 months to 100 %. CONCLUSION: Virtually all residency programs include some requirements in the 4th year (most commonly didactics and outpatient clinic) in addition to a broad array of elective experiences. Although 3 years may suffice for residents to complete ACGME requirements, a variety of factors may motivate programs to include required 4th year curricula. Future studies should explore the rationales for and possible benefits of programmatic requirements throughout 4 versus only 3 years of psychiatric training. PMID- 26895932 TI - Prevalence and Barriers to Management of Hypertension in Asia: Challenges and Opportunities in the Asian Century. PMID- 26895933 TI - [Ultrasound in dermatology: a new approximation to knowledge of the skin]. PMID- 26895931 TI - Building Research Capacity Across and Within Low- and Middle-Income Countries: The Collaborative Hubs for International Research on Mental Health. PMID- 26895934 TI - [Physical principles and general considerations]. AB - Cutaneous ultrasound is based on the application of the physical properties of ultrasound to the skin and cutaneous adnexae. Knowledge of ultrasound semiology, artifacts and the application of Doppler examination allows deeper study of the biology and diseases of the skin and its adnexae. PMID- 26895935 TI - [Ultrasound applied to the management of malignant melanoma]. AB - In the last few decades, the role of cutaneous ultrasound has increased in dermatology. This technique currently has multiple applications, both in inflammatory and tumoural disease. Indeed, melanoma is one of the tumours benefitting most from technological advances in ultrasound, both for initial diagnosis and for follow-up. Today, cutaneous ultrasound is a noninvasive diagnostic technique, whose main applications in melanoma are to determine tumoural thickness and analyse intratumoural vascularisation. This allows prognostic factors to be determined in real time and contributes to the diagnosis of subcutaneous and nodal metastases during initial staging and follow-up with a view to reducing morbidity and mortality. PMID- 26895936 TI - [Ultrasound in the management of non-melanoma skin cancer]. AB - Cutaneous ultrasound plays an important role in the study and management of non melanoma skin cancer. Among other factors, this technique contributes to the diagnosis and differential diagnosis of these tumours, the establishment of their size and relation to neighbouring structures, the delimitation of surgical margins, and the detection of subclinical and recurrent lesions. The present article analyses the role of cutaneous ultrasound in the field of non-melanoma skin cancer (basal and squamous cell carcinomas, lymphomas and dermatofibrosarcoma) through a literature review. PMID- 26895937 TI - [Ultrasound in the management of benign cutaneous tumours]. AB - Cutaneous ultrasound carried out by dermatologists is an emerging diagnostic technique that complements the clinical diagnosis of benign cutaneous tumours by providing important information on their structure, their relation to neighbouring structures, and the degree of vascularisation. One of the main key points in the development of this technique for use in cutaneous tumours, which will be discussed in detail, is adequate surgical planning and monitoring of some minor ambulatory surgery techniques, such as drainage or infiltrations. Likewise, cutaneous ultrasound is also useful in the diagnosis of subcutaneous nodules, without clinical/dermoscopic manifestations, and in their differential diagnosis with malignant tumours. PMID- 26895938 TI - [Ultrasound in the management of inflammatory dermatosis]. AB - Cutaneous ultrasound is a dermatological diagnostic imaging technique based on the interaction of high-frequency ultrasounds with the skin. Because it is non invasive, rapid and accessible, it has increasingly wide clinical applications. This article reviews its use in the management of inflammatory dermatological diseases. PMID- 26895939 TI - [Ultrasound examination of hidradenitis suppurativa]. AB - Hidradenitis suppurativa is a debilitating chronic, recurrent, inflammatory cutaneous disease of the hair follicle that usually presents with painful, deep and inflamed lesions in the areas of the body with apocrine glands, most frequently the axillary, groin and anogenital regions. This entity is difficult to manage since it can be difficult to determine the true nature and extension of the lesions. Cutaneous ultrasound allows real-time visualization of the cutaneous structures under examination, defining the type of lesion, its anatomical extension, and the degree of inflammatory activity, which affects adequate patient management. The present review analyses the importance of ultrasound in the assessment of patients with hidradenitis suppurativa. PMID- 26895940 TI - [Ultrasound in the management of nail disease]. AB - Nail diseases are a diagnostic challenge and high-frequency ultrasound with colour Doppler is a simple and painless diagnostic test that can often be useful. Ultrasound allows real-time evaluation of the anatomical structures of the nail and its vascularisation. The present study reviews the literature on ultrasound findings in the normal nail and in inflammatory and tumoural disease. PMID- 26895941 TI - [Color Doppler ultrasound of the scalp and hair]. AB - Color Doppler ultrasound is an imaging technique that allows the study of frequent diseases of the scalp and hair. This examination provides anatomical and functional information in real time that can reveal the extent, activity or severity of common diseases in a non-invasive way, and allows monitoring of their treatment. PMID- 26895943 TI - [Cutaneous ultrasound and dermal fillers]. AB - Requests for fillers or dermatological implants have dramatically increased in dermatology consultations in the last few years, either for the correction of superficial age-related wrinkles and cutaneous creases or to increase the volume of specific areas (cheeks, lips...). Dermatologists are often the first professionals to provide these treatments. Nevertheless, in other situations, the patients have already been treated, and many of them do not know the type of material that has been implanted or may even deny previous treatment, even when evident on clinical examination. In these occasions, cutaneous ultrasound is an effective and reliable tool for the real-time diagnosis of the kind of implant that has been used, its location, and the study of its possible complications. PMID- 26895942 TI - [Ultrasound in pediatric dermatology]. AB - Cutaneous ultrasound is particularly useful in pediatric dermatology to diagnose numerous diseases without the need to use invasive tests. The present articles reviews some frequent dermatological entities in children whose study can be simplified through cutaneous ultrasound. This article also provides practical recommendations reported in the literature that may facilitate ultrasound examination, with special mention of benign tumoural disease, both congenital and acquired, and vascular anomalies. PMID- 26895944 TI - [Interventional ultrasound]. AB - High-frequency ultrasound has become increasingly used in dermatology. This technique is accessible, non-invasive, and rapid and provides information in real time. Consequently, it has become of great diagnostic value in dermatology. However, high-frequency ultrasound also has a promising future as a complementary technique in interventional diagnostic procedures, even though its application in this field has been little studied by dermatologists. PMID- 26895945 TI - Commentary on 'The Clinical Relevance of Cardiac Troponin Assessment in Patients Undergoing Carotid Endarterectomy'. PMID- 26895947 TI - MetaCRAM: an integrated pipeline for metagenomic taxonomy identification and compression. AB - BACKGROUND: Metagenomics is a genomics research discipline devoted to the study of microbial communities in environmental samples and human and animal organs and tissues. Sequenced metagenomic samples usually comprise reads from a large number of different bacterial communities and hence tend to result in large file sizes, typically ranging between 1-10 GB. This leads to challenges in analyzing, transferring and storing metagenomic data. In order to overcome these data processing issues, we introduce MetaCRAM, the first de novo, parallelized software suite specialized for FASTA and FASTQ format metagenomic read processing and lossless compression. RESULTS: MetaCRAM integrates algorithms for taxonomy identification and assembly, and introduces parallel execution methods; furthermore, it enables genome reference selection and CRAM based compression. MetaCRAM also uses novel reference-based compression methods designed through extensive studies of integer compression techniques and through fitting of empirical distributions of metagenomic read-reference positions. MetaCRAM is a lossless method compatible with standard CRAM formats, and it allows for fast selection of relevant files in the compressed domain via maintenance of taxonomy information. The performance of MetaCRAM as a stand-alone compression platform was evaluated on various metagenomic samples from the NCBI Sequence Read Archive, suggesting 2- to 4-fold compression ratio improvements compared to gzip. On average, the compressed file sizes were 2-13 percent of the original raw metagenomic file sizes. CONCLUSIONS: We described the first architecture for reference-based, lossless compression of metagenomic data. The compression scheme proposed offers significantly improved compression ratios as compared to off-the shelf methods such as zip programs. Furthermore, it enables running different components in parallel and it provides the user with taxonomic and assembly information generated during execution of the compression pipeline. AVAILABILITY: The MetaCRAM software is freely available at http://web.engr.illinois.edu/~mkim158/metacram.html. The website also contains a README file and other relevant instructions for running the code. Note that to run the code one needs a minimum of 16 GB of RAM. In addition, virtual box is set up on a 4GB RAM machine for users to run a simple demonstration. PMID- 26895948 TI - Analysis of silver and gold nanoparticles in environmental water using single particle-inductively coupled plasma-mass spectrometry. AB - The production and use of engineering nanomaterials (ENMs) leads to the release of manufactured or engineered nanoparticles into environment. The quantification and characterization of ENMs are crucial for the assessment of their environmental fate, transport behavior and health risks to humans. To analyze the size distribution and particle number concentration of AgNPs and AuNPs in environmental water and track their stability at low number concentration, a systematic study on SP-ICPMS was presented. The Poisson statistics was used to discuss the effect of dwell time and particle number concentration theoretically on the detection of NPs in solution by SP-ICPMS. The dynamic range of SP-ICPMS is approximately two orders of magnitude. The size detection limits for silver and gold nanoparticle in ultrapure water are 20 and 19nm respectively. The detection limit of nanoparticle number concentration is 8*10(4)particlesL(-1). Size distribution of commercial silver and gold nanoparticle dispersions is determined by SP-ICP-MS, which was in accordance with the TEM results. High particle concentration recoveries of spiked AgNPs and AuNPs are obtained (80-108% and 85 107% for AgNPs and AuNPs respectively in ultrapure and filtered natural water). It indicates that SP-ICPMS can be used to detect AgNPs and AuNPs. The filtration study with different membranes showed that filtration might be a problematic pre treatment method for the detection of AgNPs and AuNPs in environmental water. Furthermore, the stability of citrate-coated AgNPs and tannic acid-coated AuNPs spiked into filtrated natural and waste water matrix was also studied at low concentration using SP-ICP-MS measurements. Dissolution of AgNPs was observed while AuNPs was stable during a ten day incubation period. Finally SP-ICPMS was used to analyze NPs in natural water and waste water. The results indicate that SP-ICPMS can be used to size metallic nanoparticles sensitively of low concentration under realistic environmental conditions. PMID- 26895946 TI - Wnt-5a-regulated miR-101b controls COX2 expression in hippocampal neurons. AB - BACKGROUND: Wnt-5a is a member of the WNT family of secreted lipoglycoproteins, whose expression increases during development; moreover, Wnt-5a plays a key role in synaptic structure and function in the adult nervous system. However, the mechanism underlying these effects is still elusive. MicroRNAs (miRNAs) are a family of small non-coding RNAs that control the gene expression of their targets through hybridization with complementary sequences in the 3' UTR, thereby inhibiting the translation of the target proteins. Several evidences indicate that the miRNAs are actively involved in the regulation of neuronal function. RESULTS: In the present study, we examined whether Wnt-5a modulates the levels of miRNAs in hippocampal neurons. Using PCR arrays, we identified a set of miRNAs that respond to Wnt-5a treatment. One of the most affected miRNAs was miR-101b, which targets cyclooxygenase-2 (COX2), an inducible enzyme that converts arachidonic acid to prostanoids, and has been involved in the injury/inflammatory response, and more recently in neuronal plasticity. Consistent with the Wnt-5a regulation of miR-101b, this Wnt ligand regulates COX2 expression in a time dependent manner in cultured hippocampal neurons. CONCLUSION: The biological processes induced by Wnt-5a in hippocampal neurons, involve the regulation of several miRNAs including miR-101b, which has the capacity to regulate several targets, including COX-2 in the central nervous system. PMID- 26895949 TI - Liver fat in adults with GH deficiency: comparison to matched controls and the effect of GH replacement. AB - CONTEXT: Existing data regarding the association between growth hormone deficiency (GHD) and liver fat content are conflicting. OBJECTIVE: We aimed (i) to assess intrahepatocellular lipid (IHCL) content in hypopituitary adults with GHD compared to matched controls and (ii) to evaluate the effect of growth hormone (GH) replacement on IHCL content. DESIGN: Cross-sectional comparison and controlled intervention study. PATIENTS, PARTICIPANTS: Cross-sectional comparison: Twenty-two hypopituitary adults with GHD and 44 healthy controls matched for age, BMI, gender and ethnicity. Intervention study: nine GHD patients starting GH replacement (GH Rx group) and nine GHD patients not starting replacement therapy (non-GH Rx group). INTERVENTION: Intervention study: GH replacement for 6 months in the GH Rx group, dosage was titrated to achieve normal IGF-1 levels. MAIN OUTCOME MEASURES: HCL content determined by proton magnetic resonance spectroscopy ((1) H MRS). RESULTS: Cross-sectional Comparison: There was no difference in IHCL content between GHD patients and healthy controls (1.89% (0.30, 4.03) vs 1.14% (0.22, 2.32); P = 0.2), and the prevalence of patients with hepatic steatosis (IHCL of >= 5.56%) was similar in the two groups (22.7% vs 15.9%; chi-square probability = 0.4). Intervention study: The change in IHCL content over 6 months did not differ between the GH Rx group and the non-GH Rx group (-0.63 +/- 4.53% vs + 0.11 +/- 1.46%; P = 0.6). CONCLUSIONS: In our study, liver fat content and the prevalence of hepatic steatosis did not differ between hypopituitary adults with GHD and matched controls. In GHD patients, GH replacement had no effect on liver fat content. PMID- 26895950 TI - Prevalence of marijuana use does not differentially increase among youth after states pass medical marijuana laws: Commentary on and reanalysis of US National Survey on Drug Use in Households data 2002-2011. AB - There is considerable interest in the effects of medical marijuana laws (MML) on marijuana use in the USA, particularly among youth. The article by Stolzenberg et al. (2015) "The effect of medical cannabis laws on juvenile cannabis use" concludes that "implementation of medical cannabis laws increase juvenile cannabis use". This result is opposite to the findings of other studies that analysed the same US National Survey on Drug Use in Households data as well as opposite to studies analysing other national data which show no increase or even a decrease in youth marijuana use after the passage of MML. We provide a replication of the Stolzenberg et al. results and demonstrate how the comparison they are making is actually driven by differences between states with and without MML rather than being driven by pre and post-MML changes within states. We show that Stolzenberg et al. do not properly control for the fact that states that pass MML during 2002-2011 tend to already have higher past-month marijuana use before passing the MML in the first place. We further show that when within-state changes are properly considered and pre-MML prevalence is properly controlled, there is no evidence of a differential increase in past-month marijuana use in youth that can be attributed to state MML. PMID- 26895951 TI - The Oncological Value of Omentectomy in Gastrectomy for Cancer. AB - AIM: The aim of this study was to determine the oncologic value of omentectomy in patients undergoing gastrectomy for gastric cancer. METHODS: All consecutive patients with gastric cancer that underwent gastrectomy with curative intent between April 2012 and August 2015 were prospectively analyzed. The greater omentum was separately marked during operation and pathologically evaluated for the presence of omental lymph nodes and tumor deposits. RESULTS: In total, 50 patients were included. The greater omentum harbored lymph nodes in nine (18 %) patients. The omental lymph nodes contained metastases in one (2 %) patient, still free of disease after 20 months. Omental tumor deposits were found in four (8 %) patients; one died <30 days postoperative and three developed peritoneal carcinomatosa after 4, 4, and 8 months. Patients with omental tumor deposits had a significantly reduced 1-year disease-free survival compared to patients without tumor deposits (0 vs. 58.7 %, p = 0.003). No predictive factors for omental tumor involvement could be identified. CONCLUSION: Omental lymph node metastases or tumor deposits are present in 10 % of Western European patients undergoing gastrectomy for gastric cancer. Omentectomy has a prognostic and oncologic value in the curative treatment of patients with gastric cancer. As no predictive factors for omental tumor involvement could be identified, omentectomy should be the standard in gastrectomy for gastric cancer patients. PMID- 26895952 TI - Clinical Burden of Laparoscopic Feeding Jejunostomy Tubes. AB - INTRODUCTION: Feeding jejunostomies (J tubes) provide enteral nutrition when oral and gastric routes are not options. Despite their prevalence, there is a paucity of literature regarding their efficacy and clinical burden. METHODS: All laparoscopic J tubes placed over a 5-year period were retrospectively reviewed. Clinical burden was measured by number of clinical contact events (tube-related clinic visits, phone calls, ED visits) and morbidity (dislodgement, clogging, tube fracture, infection, other). Tube replacements were also recorded. RESULTS: One hundred fifty-one patients were included. Fifty-nine percent had associated malignancy, and 35 % were placed for nutritional prophylaxis. Mean time to J tube removal was 146 days. J tubes were expected to be temporary in >90 % but only 50 % had sufficient oral intake for removal. Tubes were removed prematurely due to patient intolerance in 8 %. Mortality was 0 %. Morbidity was 51 % and included clogging (12 %), tube fracture (16 %), dislodgement (25 %), infection (18 %) and "other" (leaking, erosion, etc.) in 17 %. The median number of adverse events per J tube was 2(0-8). Mean number of clinic phone calls was 2.5(0-22), ED visits 0.5(0-7), and clinic visits 1.4(0-13), with 82 % requiring more than one J tube related clinic visit. Unplanned replacements occurred in 40 %. CONCLUSION: While necessary for some patients, J tubes are associated with high clinical burden. PMID- 26895953 TI - Biomarker evaluation as a potential cause of gender differences in obesity paradox among patients with STEMI. AB - BACKGROUND: Obesity with its worldwide growing prevalence is an established cardiovascular risk factor with increased morbidity and mortality. However, the phenomenon, that mild to moderate obesity seems to represent a protective effect on diseases has been termed the "obesity paradox". METHODS: We retrospectively assessed 529 patients (72.6% male, mean age 59.7+/-12.7years) admitted with ST elevation myocardial infarction (STEMI). The female and male study populations were separated into four body mass index (BMI) groups: <=24.9kg/m(2), 25.0 29.9kg/m(2), 30.0-34.9kg/m(2) and >=35.0kg/m(2). Blood samples of high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c) were analyzed. RESULTS: With increasing BMI group the rate of major adverse cardiac events (MACE) decreased in all patients (test for trend p=0.041). No gender difference between MACE and BMI could be noticed (p=0.16). A higher risk for MACE was indicated in group BMI <=18.5kg/m(2) in comparison to group BMI 25.0 29.9kg/m(2) (OR: 7.93; 95% CI: 1.75-35.89; p=0.0091), whereas group BMI 30.0 34.9kg/m(2) was significant associated with a lower risk in comparison to group BMI 25.0-29.9kg/m(2) (OR: 0.65; 95% CI: 0.21-1.96; p=0.044). An association between HDL-c (p=0.55) or LDL-c (p=0.10) and MACE could not be detected. CONCLUSION: The study demonstrates that patients with STEMI and a BMI of 30.0 34.9kg/m(2) have a decreased risk for MACE compared to patients with normal BMI. No gender related differences were indicated. An association between MACE and lipoproteins could not be detected. PMID- 26895955 TI - Effects of Abdominoplasty on Intra-Abdominal Pressure and Pulmonary Function. AB - BACKGROUND: Abdominal wall weakness is a consequence of rectus abdominis diastasis and flaccidity of the myofascial component. A degree of plicature of the rectus abdominis generates an increase of intra-abdominal pressure (IAP), which may result in an increase of intrathoracic pressure, thus affecting thoracic hemodynamics and leading to inadequate ventilation. OBJECTIVES: To assess changes generated by plicature of the rectus abdominis on IAP and pulmonary function in patients undergoing abdominoplasty. METHODS: A total of 10 female patients with abdominal ptosis were included. Chronic smokers and patients with respiratory co-morbidities were excluded. The IAP was measured using a modified Kron's trans-bladder technique. Pulmonary function was assessed by pulmonary compliance (P-Comp) and was calculated with parameters provided by the mechanical ventilator. Both were calculated before and after plicature. RESULTS: The mean values for IAP before and after plicature were 6.6 and 9.3 mmHg respectively. Before plicature, the mean P-Comp value was 38.97 mL/cm of water, and after it was 36.54 mL/cm. Both differences were statistically significant. CONCLUSIONS: Based on the results obtained, it is possible to conclude that plicature of the rectus abdominis generates significant physiological changes, such as an increase in IAP and a decrease of P-Comp, which do not have a clinically relevant impact on healthy individuals. Measuring IAP with the modified technique and the assessment of pulmonary function using P-Comp are both reliable and provide a more accurate correlation with such physiologic changes. LEVEL OF EVIDENCE 3: Therapeutic. PMID- 26895954 TI - Prolonged pemetrexed pretreatment augments persistence of cisplatin-induced DNA damage and eliminates resistant lung cancer stem-like cells associated with EMT. AB - BACKGROUND: Lung cancer is the leading cause of cancer-related mortality, and new therapeutic options are urgently needed. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers, with the current standard regimen of care for NSCLC including chemotherapy with pemetrexed as a single agent or in combination with platinum-based agents, e.g. cisplatin. Pemetrexed is a folic acid antagonist that inhibits the synthesis of precursor nucleotides, whereas cisplatin directly induces DNA adducts, the repair of which is dependent on sufficiently high nucleotide levels. In the clinical setting, the pemetrexed cisplatin combination therapy is administered concomitantly. We hypothesized that prolonged pretreatment with pemetrexed could be beneficial, as prior depletion of nucleotide pools could sensitize cancer cells to subsequent treatment with cisplatin. METHODS: NSCLC A549 and H460 cells were treated with pemetrexed for 72 h. In addition, 24 h of cisplatin treatment was initiated at day 1, 2 or 3 resulting in either simultaneous pemetrexed application or pemetrexed pretreatment for 24 or 48 h, respectively. Cell growth and colony formation as well as senescence induction were quantified after treatment. Cell cycle distribution and phosphorylation of histone variant H2AX as a surrogate marker for DNA damage was quantified by flow cytometry. Relative changes in gene expression were determined by quantitative real time PCR. RESULTS: Prolonged pemetrexed pretreatment for 48 h prior to cisplatin treatment maximally delayed long-term cell growth and significantly reduced the number of recovering clones. Moreover, apoptosis and senescence were augmented and recovery from treatment induced DNA damage was delayed. Interestingly, a cell population was identified that displayed an epithelial-to-mesenchymal transition (EMT) and which had a stem cell phenotype. This population was highly resistant to concomitant pemetrexed cisplatin treatment but was sensitized by pemetrexed pretreatment. CONCLUSIONS: Adaptation of the standard treatment schedule to include pretreatment with pemetrexed optimizes the anticancer efficiency of pemetrexed-cisplatin combination therapy, which correlates with a persistence of treatment-induced DNA damage. Therefore, this study warrants further investigations to elucidate whether such an adaptation could enhance the effectiveness of the standard clinical treatment regimen. In addition, a subpopulation of therapy resistant cells with EMT and cancer stem cell features was identified that was resistant to the standard treatment regimen but sensitive to pemetrexed pretreatment combined with cisplatin. PMID- 26895956 TI - Lessons Learned from a National Cosmetic Surgery Insurance Database. PMID- 26895957 TI - Response to "Lessons Learned from a National Cosmetic Surgery Insurance Database". PMID- 26895958 TI - Safety of Aesthetic Surgery in the Overweight Patient: Analysis of 127,961 Patients. AB - BACKGROUND: Nearly 70% of US adults are overweight or obese (body mass index, BMI >= 25 kg/m(2)), and more such patients are seeking aesthetic surgery. Previous studies have evaluated surgical risk in obese (BMI >= 30) or morbidly obese (BMI >= 40) patients, with mixed results. OBJECTIVES: This study evaluates BMI 25 to 29.9 and BMI >= 30 as independent risk factors of major complications following aesthetic surgery in a large, prospective, multi-center database. METHODS: A prospective cohort of patients undergoing aesthetic surgery between 2008 and 2013 was identified from the CosmetAssure database (Birmingham, AL). BMI was evaluated as a risk factor for major complications, defined as complications requiring an emergency room visit, hospital admission, or reoperation within 30 days of the procedure. Multivariate analysis controlled for variables including age, gender, smoking, diabetes, combined procedures, and type of surgical facility. RESULTS: Of the 127,961 patients, 36.2% had BMI >= 25. Overweight patients were more likely to be male (12.5%), diabetic (3.3%), nonsmokers (92.8%), or have multiple procedures (41%). Complication rate steadily increased with BMI: 1.4% (BMI < 18.5); 1.6% (18.5-24.9); 2.3% (25-29.9); 3.1% (30-39.9); 4.2% (>=40). Infection (0.8%), venous thromboembolism (VTE, 0.4%), and pulmonary dysfunction (0.2%) were twice as common among overweight patients. Incidence of hematoma was similar in the two groups (0.9%). Complications following abdominoplasty (3.5%), liposuction (0.9%), lower body lift (8.8%), or combined breast and body procedures (4.2%) were significantly higher in overweight patients. On multivariate analysis, being overweight (BMI 25-29.9) or obese (BMI >= 30) were independent predictors of any complication (Relative Risk, RR 1.17 and 1.51), especially infection (RR 1.63 and 2.73), and VTE (RR 1.67 and 2.56). CONCLUSIONS: Overweight (BMI 25-29.9) and obesity (BMI >= 30) are both independent risk factors for post-operative infection and VTE in aesthetic surgery. LEVEL OF EVIDENCE 2: Risk. PMID- 26895959 TI - Association Between MIF-AS rs755622 and Nephrolithiasis Risk in a Chinese Population. AB - BACKGROUND Single-nucleotide polymorphisms (SNPs) located at lncRNA may affect the stability and splicing processes of mRNA formation, which result in the alteration of its interacting partners. The SNP rs755622 within exon of antisense lncRNA MIF- AS and promoter of MIF was implicated in renal disease risk. MATERIAL AND METHODS In this case-control study, we genotyped the SNP rs755622 in 230 patients diagnosed with nephrolithiasis and 250 controls in a Chinese population. RESULTS We found that the rs755622 CG and CC genotypes had a significantly increased nephrolithiasis risk (adjusted OR=1.52, 95% CI=1.03-2.25; OR=2.63, 95% CI=1.21-5.72, P=0.015), compared with GG genotype in the additive model. The rs755622 C carriers (GC/CC) had an adjusted OR (95% CI) of 1.65 (1.14-2.39, P=0.016), compared with the GG genotype in the dominant model. This hazardous effect was more pronounced in subgroup age >46, BMI >24, hypertension, ever smoking, and ever drinking subjects. Moreover, we found that rs755622 could modulate the function of MIF-AS by influencing its folding. CONCLUSIONS These results indicate that the MIF-AS rs755622 polymorphism may have a crucial role in the development of nephrolithiasis. PMID- 26895960 TI - Cancer Cell-derived Exosomes Induce Mitogen-activated Protein Kinase-dependent Monocyte Survival by Transport of Functional Receptor Tyrosine Kinases. AB - Tumor-associated macrophages (TAM) play pivotal roles in cancer initiation and progression. Monocytes, the precursors of TAMs, normally undergo spontaneous apoptosis within 2 days, but can subsist in the inflammatory tumor microenvironment for continuous survival and generation of sufficient TAMs. The mechanisms underlying tumor-driving monocyte survival remain obscure. Here we report that cancer cell-derived exosomes were crucial mediators for monocyte survival in the inflammatory niche. Analysis of the survival-promoting molecules in monocytes revealed that cancer cell-derived exosomes activated Ras and extracellular signal-regulated kinases in the mitogen-activated protein kinase (MAPK) pathway, resulting in the prevention of caspase cleavage. Phosphorylated receptor tyrosine kinases (RTKs), such as phosphorylated epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER-2), were abundantly expressed in cancer cell-derived exosomes. Knock-out of EGFR or/and HER-2, or alternatively, inhibitors against their phosphorylation significantly disturbed the exosome-mediated activation of the MAPK pathway, inhibition of caspase cleavage, and increase in survival rate in monocytes. Moreover, the deprived survival-stimulating activity of exosomes due to null expression of EGFR and HER-2 could be restored by activation of another RTK, insulin receptor. Overall, our study uncovered a mechanism of tumor-associated monocyte survival and demonstrated that cancer cell-derived exosomes can stimulate the MAPK pathway in monocytes through transport of functional RTKs, leading to inactivation of apoptosis-related caspases. This work provides insights into the long sought question on monocyte survival prior to formation of plentiful TAMs in the tumor microenvironment. PMID- 26895961 TI - Regulator of G Protein Signaling 7 (RGS7) Can Exist in a Homo-oligomeric Form That Is Regulated by Galphao and R7-binding Protein. AB - RGS (regulator of G protein signaling) proteins of the R7 subfamily (RGS6, -7, 9, and -11) are highly expressed in neurons where they regulate many physiological processes. R7 RGS proteins contain several distinct domains and form obligatory dimers with the atypical Gbeta subunit, Gbeta5 They also interact with other proteins such as R7-binding protein, R9-anchoring protein, and the orphan receptors GPR158 and GPR179. These interactions facilitate plasma membrane targeting and stability of R7 proteins and modulate their activity. Here, we investigated RGS7 complexes using in situ chemical cross-linking. We found that in mouse brain and transfected cells cross-linking causes formation of distinct RGS7 complexes. One of the products had the apparent molecular mass of ~150 kDa on SDS-PAGE and did not contain Gbeta5 Mass spectrometry analysis showed no other proteins to be present within the 150-kDa complex in the amount close to stoichiometric with RGS7. This finding suggested that RGS7 could form a homo oligomer. Indeed, co-immunoprecipitation of differentially tagged RGS7 constructs, with or without chemical cross-linking, demonstrated RGS7 self association. RGS7-RGS7 interaction required the DEP domain but not the RGS and DHEX domains or the Gbeta5 subunit. Using transfected cells and knock-out mice, we demonstrated that R7-binding protein had a strong inhibitory effect on homo oligomerization of RGS7. In contrast, our data indicated that GPR158 could bind to the RGS7 homo-oligomer without causing its dissociation. Co-expression of constitutively active Galphao prevented the RGS7-RGS7 interaction. These results reveal the existence of RGS protein homo-oligomers and show regulation of their assembly by R7 RGS-binding partners. PMID- 26895963 TI - The One-carbon Carrier Methylofuran from Methylobacterium extorquens AM1 Contains a Large Number of alpha- and gamma-Linked Glutamic Acid Residues. AB - Methylobacterium extorquens AM1 uses dedicated cofactors for one-carbon unit conversion. Based on the sequence identities of enzymes and activity determinations, a methanofuran analog was proposed to be involved in formaldehyde oxidation in Alphaproteobacteria. Here, we report the structure of the cofactor, which we termed methylofuran. Using an in vitro enzyme assay and LC-MS, methylofuran was identified in cell extracts and further purified. From the exact mass and MS-MS fragmentation pattern, the structure of the cofactor was determined to consist of a polyglutamic acid side chain linked to a core structure similar to the one present in archaeal methanofuran variants. NMR analyses showed that the core structure contains a furan ring. However, instead of the tyramine moiety that is present in methanofuran cofactors, a tyrosine residue is present in methylofuran, which was further confirmed by MS through the incorporation of a (13)C-labeled precursor. Methylofuran was present as a mixture of different species with varying numbers of glutamic acid residues in the side chain ranging from 12 to 24. Notably, the glutamic acid residues were not solely gamma-linked, as is the case for all known methanofurans, but were identified by NMR as a mixture of alpha- and gamma-linked amino acids. Considering the unusual peptide chain, the elucidation of the structure presented here sets the basis for further research on this cofactor, which is probably the largest cofactor known so far. PMID- 26895962 TI - Calcitonin and Amylin Receptor Peptide Interaction Mechanisms: INSIGHTS INTO PEPTIDE-BINDING MODES AND ALLOSTERIC MODULATION OF THE CALCITONIN RECEPTOR BY RECEPTOR ACTIVITY-MODIFYING PROTEINS. AB - Receptor activity-modifying proteins (RAMP1-3) determine the selectivity of the class B G protein-coupled calcitonin receptor (CTR) and the CTR-like receptor (CLR) for calcitonin (CT), amylin (Amy), calcitonin gene-related peptide (CGRP), and adrenomedullin (AM) peptides. RAMP1/2 alter CLR selectivity for CGRP/AM in part by RAMP1 Trp-84 or RAMP2 Glu-101 contacting the distinct CGRP/AM C-terminal residues. It is unclear whether RAMPs use a similar mechanism to modulate CTR affinity for CT and Amy, analogs of which are therapeutics for bone disorders and diabetes, respectively. Here, we reproduced the peptide selectivity of intact CTR, AMY1 (CTR.RAMP1), and AMY2 (CTR.RAMP2) receptors using purified CTR extracellular domain (ECD) and tethered RAMP1- and RAMP2-CTR ECD fusion proteins and antagonist peptides. All three proteins bound salmon calcitonin (sCT). Tethering RAMPs to CTR enhanced binding of rAmy, CGRP, and the AMY antagonist AC413. Peptide alanine-scanning mutagenesis and modeling of receptor-bound sCT and AC413 supported a shared non-helical CGRP-like conformation for their TN(T/V)G motif prior to the C terminus. After this motif, the peptides diverged; the sCT C-terminal Pro was crucial for receptor binding, whereas the AC413/rAmy C terminal Tyr had little or no influence on binding. Accordingly, mutant RAMP1 W84A- and RAMP2 E101A-CTR ECD retained AC413/rAmy binding. ECD binding and cell based signaling assays with antagonist sCT/AC413/rAmy variants with C-terminal residue swaps indicated that the C-terminal sCT/rAmy residue identity affects affinity more than selectivity. rAmy(8-37) Y37P exhibited enhanced antagonism of AMY1 while retaining selectivity. These results reveal unexpected differences in how RAMPs determine CTR and CLR peptide selectivity and support the hypothesis that RAMPs allosterically modulate CTR peptide affinity. PMID- 26895964 TI - Glia Maturation Factor-gamma Regulates Monocyte Migration through Modulation of beta1-Integrin. AB - Monocyte migration requires the dynamic redistribution of integrins through a regulated endo-exocytosis cycle, but the complex molecular mechanisms underlying this process have not been fully elucidated. Glia maturation factor-gamma (GMFG), a novel regulator of the Arp2/3 complex, has been shown to regulate directional migration of neutrophils and T-lymphocytes. In this study, we explored the important role of GMFG in monocyte chemotaxis, adhesion, and beta1-integrin turnover. We found that knockdown of GMFG in monocytes resulted in impaired chemotactic migration toward formyl-Met-Leu-Phe (fMLP) and stromal cell-derived factor 1alpha (SDF-1alpha) as well as decreased alpha5beta1-integrin-mediated chemoattractant-stimulated adhesion. These GMFG knockdown impaired effects could be reversed by cotransfection of GFP-tagged full-length GMFG. GMFG knockdown cells reduced the cell surface and total protein levels of alpha5beta1-integrin and increased its degradation. Importantly, we demonstrate that GMFG mediates the ubiquitination of beta1-integrin through knockdown or overexpression of GMFG. Moreover, GMFG knockdown retarded the efficient recycling of beta1-integrin back to the plasma membrane following normal endocytosis of alpha5beta1-integrin, suggesting that the involvement of GMFG in maintaining alpha5beta1-integrin stability may occur in part by preventing ubiquitin-mediated degradation and promoting beta1-integrin recycling. Furthermore, we observed that GMFG interacted with syntaxin 4 (STX4) and syntaxin-binding protein 4 (STXBP4); however, only knockdown of STXBP4, but not STX4, reduced monocyte migration and decreased beta1 integrin cell surface expression. Knockdown of STXBP4 also substantially inhibited beta1-integrin recycling in human monocytes. These results indicate that the effects of GMFG on monocyte migration and adhesion probably occur through preventing ubiquitin-mediated proteasome degradation of alpha5beta1 integrin and facilitating effective beta1-integrin recycling back to the plasma membrane. PMID- 26895966 TI - Potential predictors of nipple trauma from an in-home breastfeeding programme: A cross-sectional study. AB - BACKGROUND: Australian breastfeeding rates fall significantly in the months following birth, often as a result of breastfeeding complications. AIM: To explore the potential risk factors for nipple trauma and breast engorgement in a group of women who were referred to the in home breastfeeding service in Melbourne, Australia. METHOD: A retrospective, cross-sectional analyses of the maternal-infant records (n=653) from 2003 to 2007 including demographic characteristics; pregnancy, labour and birth data; the presenting complications and observational and diagnostic results. Bivariate and logistic regression analyses were conducted to explore the predictors of nipple trauma and engorgement. RESULTS: Nipple trauma was the most common presenting complication (62.9%). Logistic regression analyses identified four statistically significant predictors: facio-mandibular asymmetry (AOR 4.21, 95% CI [1.25-14.20]), inflammatory mastitis (AOR 2.99, 95% CI [1.57-5.68], nipple malignment (AOR 2.51, 95% CI [1.13-5.55]) and the cross-cradle technique (AOR 1.90, 95% CI [1.03 3.50]). Engorgement was associated with the first postpartum breastfeed being less than one-hour duration (AOR 2.01, 95% CI [1.07-3.79]). CONCLUSION: Nipple trauma was associated with commonly taught techniques that involved the cross cradle hold and manoeuvres of the breast, nipple and baby that resulted in nipple malalignment and facio-mandibular asymmetry. This practice, appeared to interfere with the baby's intra-oral function by restricting movement of the cranio cervical spine and nuchal ligament. The combination appeared to limit the baby's instinctive ability to activate neuro-sensory mammalian behaviours to freely locate and effectively draw the nipple and breast tissue without causing trauma. Changes to the first and early breastfeeding techniques are recommended. PMID- 26895967 TI - Assessing the efficacy of lateral rectus abdominis positioned stoma (LRAPS) formation in the PATRASTOM trial. PMID- 26895965 TI - Dynamin Binding Protein (Tuba) Deficiency Inhibits Ciliogenesis and Nephrogenesis in Vitro and in Vivo. AB - Dysfunction of renal primary cilia leads to polycystic kidney disease. We previously showed that the exocyst, a protein trafficking complex, is essential for ciliogenesis and regulated by multiple Rho and Rab family GTPases, such as Cdc42. Cdc42 deficiency resulted in a disruption of renal ciliogenesis and a polycystic kidney disease phenotype in zebrafish and mice. Here we investigate the role of Dynamin binding protein (also known as Tuba), a Cdc42-specific guanine nucleotide exchange factor, in ciliogenesis and nephrogenesis using Tuba knockdown Madin-Darby canine kidney cells and tuba knockdown in zebrafish. Tuba depletion resulted in an absence of cilia, with impaired apical polarization and inhibition of hepatocyte growth factor-induced tubulogenesis in Tuba knockdown Madin-Darby canine kidney cell cysts cultured in a collagen gel. In zebrafish, tuba was expressed in multiple ciliated organs, and, accordingly, tuba start and splice site morphants showed various ciliary mutant phenotypes in these organs. Co-injection of tuba and cdc42 morpholinos at low doses, which alone had no effect, resulted in genetic synergy and led to abnormal kidney development with highly disorganized pronephric duct cilia. Morpholinos targeting two other guanine nucleotide exchange factors not known to be in the Cdc42/ciliogenesis pathway and a scrambled control morpholino showed no phenotypic effect. Given the molecular nature of Cdc42 and Tuba, our data strongly suggest that tuba and cdc42 act in the same ciliogenesis pathway. Our study demonstrates that Tuba deficiency causes an abnormal renal ciliary and morphogenetic phenotype. Tuba most likely plays a critical role in ciliogenesis and nephrogenesis by regulating Cdc42 activity. PMID- 26895968 TI - Medication review in hospitalised patients to reduce morbidity and mortality. AB - BACKGROUND: Pharmacotherapy in the elderly population is complicated by several factors that increase the risk of drug-related harms and less favourable effectiveness. The concept of medication review is a key element in improving the quality of prescribing and in preventing adverse drug events. Although there is no generally accepted definition of medication review, it can be broadly defined as a systematic assessment of pharmacotherapy for an individual patient that aims to optimise patient medication by providing a recommendation or by making a direct change. Medication review performed in adult hospitalised patients may lead to better patient outcomes. OBJECTIVES: We examined whether delivery of a medication review by a physician, pharmacist or other healthcare professional leads to improvement in health outcomes of hospitalised adult patients compared with standard care. SEARCH METHODS: We searched the Specialised Register of the Cochrane Effective Practice and Organisation of Care (EPOC) Group; the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) to November 2014, as well as International Pharmaceutical Abstracts and Web of Science to May 2015. In addition, we searched reference lists of included trials and relevant reviews. We searched trials registries and contacted experts to identify additional published and unpublished trials. We applied no language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of medication review in hospitalised adult patients. We excluded trials of outclinic and paediatric patients. Our primary outcome was all-cause mortality, and secondary outcomes included hospital readmissions, emergency department contacts and adverse drug events. DATA COLLECTION AND ANALYSIS: Two review authors independently included trials, extracted data and assessed trials for risk of bias. We contacted trial authors for clarification of data and for additional unpublished data. We calculated risk ratios for dichotomous data and mean differences for continuous data (with 95% confidence intervals (CIs)). The GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach was used to assess the overall certainty of evidence for the most important outcomes. MAIN RESULTS: We identified 6600 references (4647 references in our initial review) and included 10 trials (3575 participants). Follow-up ranged from 30 days to one year. Nine trials provided mortality data (3218 participants, 466 events), with a risk ratio of 1.02 (95% CI 0.87 to 1.19) (low-certainty evidence). Seven trials provided hospital readmission data (2843 participants, 1043 events) with a risk ratio of 0.95 (95% CI 0.87 to 1.04) (high-certainty evidence). Four trials provided emergency department contact data (1442 participants, 244 events) with a risk ratio of 0.73 (95% CI 0.52 to 1.03) (low-certainty evidence). The estimated reduction in emergency department contacts of 27% (with a CI ranging from 48% reduction to 3% increase in contacts) corresponds to a number needed to treat for an additional beneficial outcome of 37 for a low-risk population and 12 for a high-risk population over one year. Subgroup and sensitivity analyses did not significantly alter our results. AUTHORS' CONCLUSIONS: We found no evidence that medication review reduces mortality or hospital readmissions, although we did find evidence that medication review may reduce emergency department contacts. However, because of short follow-up ranging from 30 days to one year, important treatment effects may have been overlooked. High-quality trials with long-term follow-up (i.e. at least up to a year) are needed to provide more definitive evidence for the effect of medication review on clinically important outcomes such as mortality, readmissions and emergency department contacts, and on outcomes such as adverse events. Therefore, if used in clinical practice, medication reviews should be undertaken as part of a clinical trial with long term follow-up. PMID- 26895969 TI - Effectiveness and safety of ShenXiong glucose injection for acute ischemic stroke: a systematic review and GRADE approach. AB - BACKGROUND: To appraise critically whether published trials of ShenXiong glucose injection for patients with acute ischemic stroke (AIS) are of sufficient quality, and in addition to rate the quality of evidence by using the GRADE approach (grading of recommendations, assessment, development, and evaluation, GRADE). METHODS: A literature search was performed in the Cochrane Library, MEDLINE, EMBASE, CBM, Chinese TCM (traditional Chinese medicine) Database, CNKI, VIP, WanFang Databases until January 2015. The limits were patients with AIS and randomized controlled trials (RCTs) or quasi-RCTs. Studies by which patients suffering intracerebral haemorrhage were excluded. RESULTS: Twelve studies fulfilled the inclusion criteria. We found significant benefits of ShenXiong glucose injection compared with conventional treatment in improving activities of daily living function at 4 weeks (MD = 34.12, 95 % CI: 29.07, 39.17), neurological function deficit at 2 weeks (MD = -5.39, 95% CI: -6.90, -3.87), 4 weeks (MD = -5.16, 95 % CI: -6.49, -3.83), and clinical effects at 4 weeks (RR = 1.17, 95% CI: 1.10, 1.24). No trials reported the effects of ShenXiong glucose injection on the risk of early, deterioration, or quality of life. No adverse events were reported within the whole follow-up period. CONCLUSIONS: The use of ShenXiong glucose injection may improve rehabilitation for patients with acute ischemic stroke, however, as the GRADE approach indicated low to moderate quality of available evidence as well as insufficient information about harm and patients preference, the recommendations were not provided for ShenXiong glucose injection taking as a therapeutic intervention to patients with acute ischemic stroke. PMID- 26895970 TI - Validation of a New Arabic Version of the Neuropathic Pain Diagnostic Questionnaire (DN4). AB - The "Douleur Neuropathique 4 (DN4) questionnaire" was developed for screening neuropathic pain. The purpose of this work was to validate the DN4 questionnaire in the standard Arabic language. First, the questionnaire was translated and semantically adapted to Arabic according to the international guidelines for cross-cultural adaptation. Second, a prospective observational study was performed to validate this questionnaire. A total of 195 patients with chronic pain (n = 99 with neuropathic pain and n = 96 without neuropathic pain) were enrolled in the study. The internal consistency Kuder-Richardson's Formula 20 for the whole DN4 questionnaire was 0.86 (P < 0.001) and the intraclass correlation coefficient 0.99 (95% CI: 0.99 to 1.00). The test-retest reliability kappa coefficient for each item ranged from 0.92 to 1.00. Using a receiver-operating characteristic (ROC) curve analysis, the areas under the curve were 0.94 and 0.97 for the 7-item DN4 and 10-item DN4, respectively. A cut-off score of 3 resulted in a sensitivity of 97.0% and a specificity of 82.3% for the 7-item DN4, while a cut-off score of 5 for the 10-item DN4 resulted in a sensitivity of 93.0% and a specificity of 95.8%. Tingling, numbness, and hypoesthesia to touch and to pricking were the most discriminating pain items. The sensitivity and specificity of the 7-item DN4 and 10-item DN4 were not influenced by either pain severity or educational level. In conclusion, this new Arabic version DN4 questionnaire is a simple, reliable, and valid tool for discriminating between neuropathic and non neuropathic pain. It represents a useful tool in clinical setting and population based studies. PMID- 26895971 TI - Computer assisted mandibular reconstruction using a custom-made titan mesh tray and removable denture based on the top-down treatment technique. AB - PURPOSE: The purpose of this report is to propose a computer assisted mandibular reconstruction procedure, utilizing a custom-made Ti-mesh tray with particulate cancellous bone and marrow, and a removable denture. This procedure was based on the top-down treatment technique, and reviews the case of a representative patient with mandibular continuity defect. METHODS: The patient was a 74-year old female with a chief complaint of facial asymmetry and masticatory dysfunction. Due to gingival carcinoma, she underwent a segmental mandibulectomy on the left mandibule. On the VR space, using 3-D reconstructed computer tomography data, the residual right-side mandibular fragment was repositioned based on the condylar position and the occlusal relation. The mandibular fragment was then mirrored for a central sagittal plane. The position of the mirrored object was slightly arranged with the occlusal relation. Through the above operations, the landmark configuration, for the custom-made Ti-mesh tray as a virtual simulation model, was fabricated. On the physical model, we produced a custom-made Ti-mesh tray with a commercial Ti-mesh sheet. Surgical treatment was carried out using the tray. The denture pattern was designed by a dental technician on the VR space, fabricated using a 3D printer, and modified to create an impression tray with resin. Using the impression, the temporary removable denture was fabricated. CONCLUSIONS: We propose a computer assisted design for a custom-made Ti-mesh tray and a removable denture, based on the Top-down treatment concept. We feel this technique is advantageous in reconstructing functional occlusion, and in accurately regaining dental and facial esthetics. PMID- 26895972 TI - Load distribution on abutment tooth, implant and residual ridge with distal extension implant-supported removable partial denture. AB - PURPOSE: The aim of this study was to evaluate the effect of implant location on load distribution in the abutment tooth, implant and residual ridge with a distal extension implant-supported removable partial denture (ISRPD). METHODS: A mandibular unilateral distal-extension edentulous simulation model was used. Implants were inserted at the second premolar (mesial implant) and second molar (distal implant) positions in the edentulous area. An experimental ISRPD was fabricated of acrylic resin with a cobalt-chromium alloy framework. Loads on the implants and abutment tooth were measured with piezoelectric force transducers. The load on the residual ridge was measured with pressure-sensitive film. A vertical load of 100N was applied at the first molar region. Measurements were made under the following three conditions: with conventional removable partial denture (CRPD), with mesial-implant-supported removable partial denture (MISRPD), and with distal-implant-supported removable partial denture (DISRPD). In each condition, the unused implants were made inactive by eliminating contact with the inner surface of the denture. RESULTS: The load on the abutment tooth was greatest with DISRPD, followed by CRPD and MISRPD (P<0.01). The load on the implant was greater with DISRPD than with MISRPD (P<0.01). The load on the residual ridge was lowest with DISRPD, followed by MISRPD and CRPD (P<0.01). CONCLUSIONS: This experimental study provided quantitative data regarding the effect of implant location on load distribution with ISRPDs. Further investigation regarding the effect of denture design on the load distribution is needed for determining the proper implant location of ISRPD. PMID- 26895973 TI - Use of thienopyridine prior to presentation with non-ST-segment elevation acute coronary syndrome and association with safety and efficacy of vorapaxar: insights from the TRACER trial. AB - BACKGROUND: Vorapaxar is effective in the prevention of secondary atherothrombotic events, although the efficacy/safety balance appears less favorable in the treatment of patients with non-ST-segment elevation (NSTE) acute coronary syndrome (ACS). We hypothesized that patients with NSTE ACS already receiving thienopyridine prior to the ACS event may show differential efficacy/safety effects with vorapaxar vs. placebo added to their standard care. METHODS: We studied 12,944 patients from the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) trial with respect to thienopyridine use before admission for the index NSTE ACS event. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, rehospitalization for ischemia, and urgent revascularization. The key secondary endpoint was a composite of cardiovascular death, myocardial infarction, and stroke. Safety endpoints were bleeding complications. RESULTS: Only 1513 patients (11.7%) were receiving thienopyridine before admission for the index NSTE ACS event. In these patients, Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) moderate/severe bleeding occurred in 5.7% treated with vorapaxar and 5.3% treated with a placebo (hazards ratio (HR) 1.10, 95% confidence interval (CI) 0.70-1.71); in thienopyridine-naive patients, the rates were 5.7% and 4.1%, respectively (HR 1.32, 95% CI 1.11-1.57; Pint=0.45). GUSTO severe bleeding in the prior thienopyridine group occurred in 0.5% of patients treated with vorapaxar and 1.3% of patients treated with placebo (HR 0.34, 95% CI 0.09-1.30); in thienopyridine-naive patients, the rates were 2.0% and 1.0%, respectively (HR 1.89, 95% CI 1.36-2.62; Pint=0.01). No interaction was observed between vorapaxar efficacy and prior thienopyridine use on the primary (adjusted Pint=0.53) or key secondary endpoints ( Pint=0.61). CONCLUSIONS: TRACER was largely conducted in thienopyridine-naive patients with unknown tolerance to multiple antiplatelet treatments. Patients receiving thienopyridine before the index event may have had an attenuated increase in bleeding when adding vorapaxar, whereas concomitantly adding vorapaxar and thienopyridine in naive patients may have uncovered a latent susceptibility to bleeding. PMID- 26895974 TI - Intramyocardial Dissecting Hematoma after Acute Myocardial Infarction Echocardiographic Features and Clinical Outcome. AB - OBJECTIVES: Intramyocardial dissecting hematoma (IDH) after acute myocardial infarction (MI) is a rare form of subacute cardiac rupture and hence management uncertainties. The objective of this study was to describe the clinical course of a small series of IDH patients and to review the available evidence for managing similar cases. METHODS: Eight IDH patients from our center had echocardiographic, coronary angiographic and clinical outcome data reviewed. PubMed was also searched for IDH following MI. Cases were divided into three groups and compared according to the dissection location. RESULTS: In our 8 patients, 3 had septal, 1 right ventricular (RV), and 4 left ventricular (LV) dissection. Five were medically treated and 3 surgically repaired. Reviewing the literature revealed 68 IDH patients, of mean age 66 +/- 10 years, 43 males. The percentage of IDH involving the LV free wall, septal, and RV free wall were 47%, 26.5%, and 26.5%, respectively. In the cohort as a whole, mortality was not different between surgically and medically treated patients (33.3% vs. 54.3%, P = 0.08), neither based on the IDH location (P = 0.49). While surgical and medical treatment of the LV free wall (20.0% vs. 40.9%, P = 0.25) and septal (46.2% vs. 60.0%, P = 0.60) were not different, surgical repair of RV free wall had significantly better survival (30.0% vs. 87.5%, P = 0.015). The LVEF (P = 0.82), mitral regurgitation (P = 0.49) failed to predict mortality. CONCLUSION: While survival following medical and surgical treatment of LV IDH is not different, patients with RV free wall dissection benefit significantly from surgical repair. PMID- 26895975 TI - Editorial. PMID- 26895976 TI - Extinction in multiple contexts: Effects on the rate of extinction and the strength of response recovery. AB - In two human predictive-learning experiments, we investigated the effects of extinction in multiple contexts on the rate of extinction and the strength of response recovery. In each experiment, participants initially received acquisition training with a target cue in one context, followed by extinction either in a different context (extinction in a single context) or in three different contexts (extinction in multiple contexts). The results of both experiments showed that conducting extinction in multiple contexts led to higher levels of responding during extinction than did extinction in a single context. Additionally, Experiment 2 showed that extinction in multiple contexts prevented ABC renewal but had no detectable impact on ABA renewal. Our results are discussed within the framework of contemporary learning theories of contextual control and extinction. PMID- 26895977 TI - Apes have eyes to the future. AB - Kano and Hirata (Current Biology, 25, 2513-2517, 2015) recently showed that apes process object and location information and anticipate the repeated presentation of such events in short film clips. Their methodology, using eyetracking, can provide a foundation for further explications of long-term prospective and episodic memory in nonverbal species. PMID- 26895978 TI - Single-trial evaluative conditioning can be moderated by instructed forgetting. AB - Evaluative conditioning (EC) is a change in the valence of a conditioned stimulus (CS) due to previous pairing with an affective unconditioned stimulus (US). Several previous studies indicate that EC is related to memory of the CS-US pairs. Previous studies, however, typically cannot distinguish between the influence of CS-US knowledge during measurement and during encoding. In addition, by measuring rather than manipulating memory, they do not test the causal effect of memory on EC. The present study employed a "directed forgetting" procedure to the EC paradigm instructing participants to either forget or remember certain CS US pairs. We found that EC effects after single learning trials were stronger for to-be-remembered than for to-be-forgotten pairs. Manipulation checks showed that the forgetting manipulation also successfully modulated memory for the target pairs and reduced both retroactive and proactive interference on memory for other pairs. Item-based analyses further demonstrated that the size of EC depended on CS-US memory. The results suggest that EC relies on available memory during measurement of the EC effect. PMID- 26895979 TI - Midsession shifts in reward probability and the control of behavioral variability. AB - Extensive research has shown that the variability of organismal behavior is great when contingent reinforcement is delayed, small, or improbable. This research has generally employed stable response-reinforcer relationships, and therefore is limited in its explanatory scope with respect to a dynamic environment. We conducted two experiments to investigate whether pigeons' conditioned pecking behavior shows anticipatory or perseverative patterns of behavioral variability when the reinforcement probability reliably changes within experimental sessions. In Experiment 1, three pigeons received alternating sessions in which the reinforcement probability (35% or 4.2%) was shifted at the midpoint of each session in the presence of the same discrete cue. Experiment 2 featured a similar design, but with the inclusion of a discrete visual cue that changed at the session midpoint, and thus unambiguously indicated reinforcement probability. Local reinforcement rates only reliably controlled response variability when a discrete visual cue was available. Without this, pigeons did not discriminate between trial types in the first halves of sessions, and showed evidence of perseveration of response variability following a within-session shift. Critically, this is the first experimental demonstration that the relationship between reinforcement probability and behavioral variability is moderated by another factor (i.e., trial position within a session). This study thus expands our understanding of the control of behavioral variability as a function of experiential factors. PMID- 26895980 TI - The contribution of agricultural insecticide use to increasing insecticide resistance in African malaria vectors. AB - The fight against malaria is increasingly threatened by failures in vector control due to growing insecticide resistance. This review examines the recent primary research that addresses the putative relationship between agricultural insecticide use and trends in insecticide resistance. To do so, descriptive evidence offered by the new research was categorized, and additional factors that impact the relationship between agricultural insecticide use and observed insecticide resistance in malaria vectors were identified. In 23 of the 25 relevant recent publications from across Africa, higher resistance in mosquito populations was associated with agricultural insecticide use. This association appears to be affected by crop type, farm pest management strategy and urban development. PMID- 26895982 TI - Drug Transport by the Blood-Aqueous Humor Barrier of the Eye. AB - The ocular barriers (cornea, blood-retinal barrier, and blood-aqueous humor barrier) make treating eye diseases with therapeutic drugs challenging. The tight capillary endothelium of the iris and the ciliary body epithelium form the blood aqueous humor barrier. The iris and ciliary body (iris-ciliary body) express a variety of drug transporters in the ATP-binding cassette and solute carrier (SLC) families. ATP-binding cassette family drug transporters that are present in the iris-ciliary body include P-glycoprotein, breast cancer resistance protein, and several multidrug resistance-associated proteins. SLC family drug transporters that are present in the iris-ciliary body include organic anion transporters, organic anion transporting polypeptides, bile acid transporters (apical sodium dependent bile salt transporter and sodium taurocholate cotransporter), organic cation transporters (novel organic cation transporter and multidrug and toxin extrusion transporter) and peptide transporters. Freshly dissected iris-ciliary body preparations actively accumulate a variety of substrates of SLC drug transporters that are expressed in the tissue. The ciliary body in vitro supports active transport in the aqueous humor-to-blood direction of several substrates of organic anion transporters and multidrug resistance-associated proteins, consistent with the subcellular localization of these transporters in the ciliary body epithelium. In vivo data suggest that drug transporters in the iris-ciliary body reduce the permeation of drugs in the direction of blood-to-aqueous humor, thereby reducing ocular drug bioavailability, and are also involved in active drug elimination from the aqueous humor. An understanding of the influence on pharmacokinetics of drug transporters in the blood-aqueous humor barrier should help improve drug delivery and efficacy in the eye. PMID- 26895981 TI - Nonclinical Pharmacokinetics, Disposition, and Drug-Drug Interaction Potential of a Novel d-Amino Acid Peptide Agonist of the Calcium-Sensing Receptor AMG 416 (Etelcalcetide). AB - AMG 416 (etelcalcetide) is a novel synthetic peptide agonist of the calcium sensing receptor composed of a linear chain of seven d-amino acids (referred to as the d-amino acid backbone) with a d-cysteine linked to an l-cysteine via a disulfide bond. AMG 416 contains four basic d-arginine residues and is a +4 charged peptide at physiologic pH with a mol. wt. of 1048.3 Da. The pharmacokinetics (PK), disposition, and potential of AMG 416 to cause drug-drug interaction were investigated in nonclinical studies with two single (14)C-labels placed either at a potentially metabolically labile acetyl position or on the d alanine next to d-cysteine in the interior of the d-amino acid backbone. After i.v. dosing, the PK and disposition of AMG 416 were similar in male and female rats. Radioactivity rapidly distributed to most tissues in rats with intact kidneys, and renal elimination was the predominant clearance pathway. No strain dependent differences were observed. In bilaterally nephrectomized rats, minimal radioactivity (1.2%) was excreted via nonrenal pathways. Biotransformation occurred primarily via disulfide exchange with endogenous thiol-containing molecules in whole blood rather than metabolism by enzymes, such as proteases or cytochrome P450s; the d-amino acid backbone remained unaltered. A substantial proportion of the plasma radioactivity was covalently conjugated to albumin. AMG 416 presents a low risk for P450 or transporter-mediated drug-drug interactions because it showed no interactions in vitro. These studies demonstrated a (14)C label on either the acetyl or the d-alanine in the d-amino acid backbone would be appropriate for clinical studies. PMID- 26895983 TI - Impact of contact on adolescents' mental health literacy and stigma: the SchoolSpace cluster randomised controlled trial. AB - OBJECTIVES: To investigate whether intergroup contact in addition to education is more effective than education alone in reducing stigma of mental illness in adolescents. DESIGN: A pragmatic cluster randomised controlled trial compared education alone with education plus contact. Blocking was used to randomly stratify classes within schools to condition. Random allocation was concealed, generated by a computer algorithm, and undertaken after pretest. Data was collected at pretest and 2-week follow-up. Analyses use an intention-to-treat basis. SETTING: Secondary schools in Birmingham, UK. PARTICIPANTS: The parents and guardians of all students in year 8 (age 12-13 years) were approached to take part. INTERVENTIONS: A 1-day educational programme in each school led by mental health professional staff. Students in the 'contact' condition received an interactive session with a young person with lived experience of mental illness. OUTCOMES: The primary outcome was students' attitudinal stigma of mental illness. Secondary outcomes included knowledge-based stigma, mental health literacy, emotional well-being and resilience, and help-seeking attitudes. RESULTS: Participants were recruited between 1 May 2011 and 30 April 2012. 769 participants completed the pretest and were randomised to condition. 657 (85%) provided follow-up data. At 2-week follow-up, attitudinal stigma improved in both conditions with no significant effect of condition (95% CI -0.40 to 0.22, p=0.5, d=0.01). Significant improvements were found in the education-alone condition compared with the contact and education condition for the secondary outcomes of knowledge-based stigma, mental health literacy, emotional well-being and resilience, and help-seeking attitudes. CONCLUSIONS: Contact was found to reduce the impact of the intervention for a number of outcomes. Caution is advised before employing intergroup contact with younger student age groups. The education intervention appeared to be successful in reducing stigma, promoting mental health knowledge, and increasing mental health literacy, as well as improving emotional well-being and resilience. A larger trial is needed to confirm these results. TRIAL REGISTRATION NUMBER: ISRCTN07406026; Results. PMID- 26895984 TI - Text messaging reminders for influenza vaccine in primary care: a cluster randomised controlled trial (TXT4FLUJAB). AB - OBJECTIVES: (1) To develop methods for conducting cluster randomised trials of text messaging interventions utilising routine electronic health records at low cost; (2) to assess the effectiveness of text messaging influenza vaccine reminders in increasing vaccine uptake in patients with chronic conditions. DESIGN: Cluster randomised trial with general practices as clusters. SETTING: English primary care. PARTICIPANTS: 156 general practices, who used text messaging software, who had not previously used text message influenza vaccination reminders. Eligible patients were aged 18-64 in 'at-risk' groups. INTERVENTIONS: Practices were randomly allocated to either an intervention or standard care arm in the 2013 influenza season (September to December). Practices in the intervention arm were asked to send a text message influenza vaccination reminder to their at-risk patients under 65. Practices in the standard care arm were asked to continue their influenza campaign as planned. BLINDING: Practices were not blinded. Analysis was performed blinded to practice allocation. MAIN OUTCOME MEASURES: Practice-level influenza vaccine uptake among at-risk patients aged 18-64 years. RESULTS: 77 practices were randomised to the intervention group (76 analysed, n at-risk patients=51,121), 79 to the standard care group (79 analysed, n at-risk patients=51,136). The text message increased absolute vaccine uptake by 2.62% (95% CI -0.09% to 5.33%), p=0.058, though this could have been due to chance. Within intervention clusters, a median 21.0% (IQR 10.2% to 47.0%) of eligible patients were sent a text message. The number needed to treat was 7.0 (95% CI -0.29 to 14.3). CONCLUSIONS: Patient follow-up using routine electronic health records is a low cost method of conducting cluster randomised trials. Text messaging reminders are likely to result in modest improvements in influenza vaccine uptake, but levels of patients being texted need to markedly increase if text messaging reminders are to have much effect. TRIAL REGISTRATION NUMBER: ISRCTN48840025. PMID- 26895985 TI - STROBE-AMS: recommendations to optimise reporting of epidemiological studies on antimicrobial resistance and informing improvement in antimicrobial stewardship. AB - OBJECTIVES: To explore the accuracy of application of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) tool in epidemiological studies focused on the evaluation of the role of antibiotics in selecting resistance, and to derive and test an extension of STROBE to improve the suitability of the tool in evaluating the quality of reporting in these area. METHODS: A three-step study was performed. First, a systematic review of the literature analysing the association between antimicrobial exposure and acquisition of methicillin-resistant Staphylococcus aureus and/or multidrug resistant Acinetobacter baumannii was performed. Second, articles were reviewed according to the STROBE checklist for epidemiological studies. Third, a set of potential new items focused on antimicrobial-resistance quality indicators was derived through an expert two-round RAND-modified Delphi procedure and tested on the articles selected through the literature review. RESULTS: The literature search identified 78 studies. Overall, the quality of reporting appeared to be poor in most areas. Five STROBE items, comprising statistical analysis and study objectives, were satisfactory in <25% of the studies. Informative abstract, reporting of bias, control of confounding, generalisability and description of study size were missing in more than half the articles. A set of 21 new items was developed and tested. The new items focused particularly on the study setting, antimicrobial usage indicators, and patients epidemiological and clinical characteristics. The performance of the new items in included studies was very low (<25%). CONCLUSIONS: Our paper reveals that reporting in epidemiological papers analysing the association between antimicrobial usage and development of resistance is poor. The implementation of the newly developed STROBE for antimicrobial stewardship (AMS) tool should enhance appropriate study design and reporting, and therefore contribute to the improvement of evidence to be used for AMS programme development and assessment. PMID- 26895987 TI - Performance and quality indicators for the management of non-cancer chronic pain: a scoping review protocol. AB - INTRODUCTION: Chronic pain is a public health problem of epidemic proportion in most countries with important physical, psychological, social and economic consequences. The management of chronic pain is complex and requires an integrated network approach between all levels of the healthcare system and the involvement of several health professionals from different disciplines. Measuring the performance of organisations that provide care to individuals with chronic pain is essential to improve quality of care and requires the use of relevant performance and quality indicators. A scoping review methodology will be used to synthesise the evidence on performance and quality indicators developed for non cancer chronic pain management across the continuum of care. METHODS AND ANALYSIS: The following electronic databases will be searched from 2000 onwards: Cochrane Effective Practice and Organisation of Care (EPOC) Review Group Specialised Register; Cochrane Library; EMBASE; PubMed; CINAHL; PsycINFO; ProQuest Dissertations and Theses. All types of studies will be included if these are concerned with performance or quality indicators in adults with chronic non cancer pain. In addition, searches will be conducted on provincial, national and international health organisations as well as health professional and scientific associations' websites. A qualitative descriptive approach will be used to describe characteristics of each indicator. All identified indicators will be classified according to dimensions covered by Donabedian and the Triple Aim frameworks. ETHICS AND DISSEMINATION: The scoping review findings will inform the development of a performance measurement system comprising a list of performance indicators with their level of evidence which can be used by stakeholders to evaluate the quality of care for individuals with chronic non-cancer pain at the patient, institutional and system level. The results will be disseminated via several knowledge translation strategies, including 2 stakeholder meetings, publication and presentation at conferences. PMID- 26895986 TI - Germline mutations in PMS2 and MLH1 in individuals with solitary loss of PMS2 expression in colorectal carcinomas from the Colon Cancer Family Registry Cohort. AB - OBJECTIVES: Immunohistochemistry for DNA mismatch repair proteins is used to screen for Lynch syndrome in individuals with colorectal carcinoma (CRC). Although solitary loss of PMS2 expression is indicative of carrying a germline mutation in PMS2, previous studies reported MLH1 mutation in some cases. We determined the prevalence of MLH1 germline mutations in a large cohort of individuals with a CRC demonstrating solitary loss of PMS2 expression. DESIGN: This cohort study included 88 individuals affected with a PMS2-deficient CRC from the Colon Cancer Family Registry Cohort. Germline PMS2 mutation analysis (long range PCR and multiplex ligation-dependent probe amplification) was followed by MLH1 mutation testing (Sanger sequencing and multiplex ligation-dependent probe amplification). RESULTS: Of the 66 individuals with complete mutation screening, we identified a pathogenic PMS2 mutation in 49 (74%), a pathogenic MLH1 mutation in 8 (12%) and a MLH1 variant of uncertain clinical significance predicted to be damaging by in silico analysis in 3 (4%); 6 (9%) carried variants likely to have no clinical significance. Missense point mutations accounted for most alterations (83%; 9/11) in MLH1. The MLH1 c.113A> G p.Asn38Ser mutation was found in 2 related individuals. One individual who carried the MLH1 intronic mutation c.677+3A>G p.Gln197Argfs*8 leading to the skipping of exon 8, developed 2 tumours, both of which retained MLH1 expression. CONCLUSIONS: A substantial proportion of CRCs with solitary loss of PMS2 expression are associated with a deleterious MLH1 germline mutation supporting the screening for MLH1 in individuals with tumours of this immunophenotype, when no PMS2 mutation has been identified. PMID- 26895988 TI - Efficacy and safety of gelatine tannate for the treatment of acute gastroenteritis in children: protocol of a randomised controlled trial. AB - INTRODUCTION: Worldwide, acute gastroenteritis in children, usually caused by viruses, leads to considerable morbidity and mortality. The treatment is aimed at preventing and treating dehydration, promoting weight gain after rehydration, and reducing the duration and severity of diarrhoea. Effective and inexpensive interventions that could add to the effect of oral rehydration therapy are of interest. Recently, in many European countries, gelatine tannate is being widely marketed for treating acute gastroenteritis. Gelatine tannate is a complex of tannic acid, which possesses astringent and anti-inflammatory properties, and a protective gelatine. Currently, there is no evidence to support the use of gelatine tannate for treating acute gastroenteritis in children and only scant evidence to support the use of gelatine tannate in adults. We aim to assess the efficacy of gelatine tannate for the treatment of acute gastroenteritis in children. METHODS AND ANALYSIS: This will be a blind, placebo-controlled, randomised trial. Children younger than 5 years of age with acute gastroenteritis defined as a change in stool consistency to loose or liquid form (according to the Bristol Stool Form scale or Amsterdam Stool Form scale) and/or an increase in the frequency of evacuations (typically >= 3 in 24 h), lasting for no longer than 5 days, will be recruited. A total of 72 children will be randomised to receive either gelatine tannate (children younger than 3 years of age will receive 250 mg, 4 times/day, and those older than 3 years of age will receive 500 mg, 4 times/day) or matching placebo for 5 days. The primary outcome measure is the duration of diarrhoea. ETHICS AND DISSEMINATION: The Bioethics Committee approved the study protocol. The findings of this trial will be submitted to a peer reviewed paediatric journal. Abstracts will be submitted to relevant national and international conferences. TRIAL REGISTRATION NUMBER: NCT02280759; Pre-results. PMID- 26895989 TI - Understanding quit decisions in primary care: a qualitative study of older GPs. AB - OBJECTIVE: To investigate the reasons behind intentions to quit direct patient care among experienced general practitioners (GPs) aged 50-60 years. DESIGN AND SETTING: Qualitative study based on semistructured interviews with GPs in the South West region of England. Transcribed interviews were analysed thematically. PARTICIPANTS: 23 GPs aged 50-60 years: 3 who had retired from direct patient care before age 60, and 20 who intended to quit direct patient care within the next 5 years. RESULTS: The analysis identified four key themes: early retirement is a viable option for many GPs; GPs have employment options other than undertaking direct patient care; GPs report feeling they are doing an (almost) undoable job; and GPs may have other aspirations that pull them away from practice. Findings from this study confirmed those from earlier research, with high workload, ageing and health, family and domestic life, and organisational change all influencing GPs' decisions about when to retire/quit direct patient care. However, in addition, GPs expressed feelings of insecurity and uncertainty regarding the future of general practice, low morale, and issues regarding accountability (appraisal and revalidation) and governance. Suggestions about how to help retain GPs within the active clinical workforce were offered, covering individual, practice and organisational levels. CONCLUSIONS: This research highlights aspects of the current professional climate for GPs that are having an impact on retirement decisions. Any future changes to policy or practice to help retain experienced GPs will benefit from this informed understanding of GPs' views. Key factors to take into account include: making the GP workload more manageable; managing change sympathetically; paying attention to GPs' own health; improving confidence in the future of general practice; and improving GP morale. PMID- 26895990 TI - Survey of pyrrolizidine alkaloids in seven varieties of Lappula squarrosa: An alternative source of heart-healthy vegetable oil. AB - INTRODUCTION: Growing demand for heart-healthy omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), is putting stress on wild fish stocks. There is now a compelling need for new and novel sources of non-traditional seed oils containing high stearidonic acid (SDA), a precursor of EPA and DHA, to reduce this demand. The seed oil of Lappula squarrosa is one of the richest sources of SDA, however, the plant has been found to contain toxic pyrrolizidine alkaloids (PAs). OBJECTIVE: In this study, the PA concentrations of seven varieties (A-G) of Lappula squarrosa were analysed to determine the most suitable varieties for commercial seed oil production. METHODS: Whilst the clean-up procedure for the PAs in the roots, flowers and leaves was on diatomaceous earth columns and finally analysed with GC EI-MS, that of the seeds was through SCX-SPE and a more sensitive HPLC-ESI-MS/MS sum parameter method was used in the analysis. RESULTS: Altogether six PAs (supinine, amabiline, intermedine, lycopsamine and 3'-acetylintermedine) including one unknown retronecine-type PA were identified with variety C recording the lowest total PA concentration (4.64 mg seneciphylline equivalents (SE)/g dry weight (d.w.)). Besides, the total PA concentrations in the seeds of Lappula squarrosa varieties ranged between 2.88 MUg PA/g and 10.36 MUg PA/g d.w. CONCLUSION: Based solely on overall PA concentrations and PA distribution, variety D (5.95 mg SE/g d.w.) was found to be a potential candidate for commercial seed oil cultivation. PMID- 26895991 TI - The establishment of efficient bioconversion, extraction, and isolation processes for the production of phyllodulcin, a potential high intensity sweetener, from sweet hydrangea leaves (Hydrangea macrophylla Thunbergii). AB - INTRODUCTION: Hydrangea leaf tea has been traditionally consumed in the far-east Asian countries and is favoured for its distinct minty-sweet taste. Phyllodulcin is identified as a key sweet-tasting compound; it is 400-800 times sweeter than sucrose. However, its extraction has not been well-documented. In an effort to optimise phyllodulcin production, pretreatment processes to accumulate phyllodulcin as a final metabolite in leaf tissue were studied, and an efficient process was established for the extraction and purification of phyllodulcin. METHODS: Phyllodulcin was structurally identified using an LC/MS system. Hydrangea leaves were processed by either hand rolling or mechanical blending, by exposing them at different drying temperatures (25 and 70 degrees C), and even by inducing bioconversion in leaf tissue. The leaf powder was extracted with various solvents (methanol, ethanol, and water) by soaking at 25 degrees C for 12 h, ultrasonication at 35 degrees C for 1 h or accelerated solvent extraction (ASE). Extracts were purified with ion exchange resins and purified using preparative HPLC. RESULTS: Traditional hand rolling and drying at 70 degrees C significantly increased phyllodulcin accumulation in the leaves. Meanwhile, more phyllodulcin was obtained from the leaves blended mechanically or converted enzymatically compared to traditionally processed ones (P < 0.05). Methanol and ethanol were superior to water as extraction media, and the greatest phyllodulcin yields obtained by ASE, soaking and ultrasonication were 21.28, 21.20 and 19.33 mg/g, respectively, when methanol was used. Highly pure phyllodulcin powder was obtained with a yield of 2.12%. CONCLUSIONS: This promising result would be beneficial to the industrial utilisation of phyllodulcin as a potential high intensity sweetener. PMID- 26895992 TI - Spathaspora allomyrinae sp. nov., a d-xylose-fermenting yeast species isolated from a scarabeid beetle Allomyrina dichotoma. AB - During an investigation of yeasts associated with insects, three strains of a d xylose-fermenting yeast species were isolated from the gut of the host beetles Allomyrina dichotoma (Coleoptera: Scarabeidae) collected on the Baotianman National Nature Reserve, Nanyan, Henan Province, China. These strains formed two elongated ascospores, which were tapered and curved at the ends in persistent asci. Sequence analyses of the D1/D2 domains of the large subunit (LSU) and small subunit (SSU) rRNA genes showed that these new strains represent a phylogenetically distinct species in the Spathaspora clade. This novel species differed from the closest species, Candida lyxosophila NRRL Y-17539T, by a 6.7 % sequence divergence (31 substitutions and 7 gaps) in the D1/D2 LSU rRNA gene and a 1.2 % divergence (17 substitutions, 4 gaps) in the SSU rRNA gene. The novel species can also be distinguished from C. lyxosophila NRRL Y-17539T in terms of the ability to assimilate myo-inositol and to grow in the presence of 0.1 % cycloheximide, as well as the inability to assimilate citrate. The name Spathaspora allomyrinae sp. nov. is proposed for this species. The type strain is NYNU 1495T ( = CICC 33057T = CBS 13924T). The MycoBank number is MB 815071. PMID- 26895993 TI - Adventurous Physical Activity Environments: A Mainstream Intervention for Mental Health. AB - Adventurous physical activity has traditionally been considered the pastime of a small minority of people with deviant personalities or characteristics that compel them to voluntarily take great risks purely for the sake of thrills and excitement. An unintended consequence of these traditional narratives is the relative absence of adventure activities in mainstream health and well-being discourses and in large-scale governmental health initiatives. However, recent research has demonstrated that even the most extreme adventurous physical activities are linked to enhanced psychological health and well-being outcomes. These benefits go beyond traditional 'character building' concepts and emphasize more positive frameworks that rely on the development of effective environmental design. Based on emerging research, this paper demonstrates why adventurous physical activity should be considered a mainstream intervention for positive mental health. Furthermore, the authors argue that understanding how to design environments that effectively encourage appropriate adventure should be considered a serious addition to mainstream health and well-being discourse. PMID- 26895995 TI - Mitochondria and Mitochondrial ROS in Cancer: Novel Targets for Anticancer Therapy. AB - Mitochondria are indispensable for energy metabolism, apoptosis regulation, and cell signaling. Mitochondria in malignant cells differ structurally and functionally from those in normal cells and participate actively in metabolic reprogramming. Mitochondria in cancer cells are characterized by reactive oxygen species (ROS) overproduction, which promotes cancer development by inducing genomic instability, modifying gene expression, and participating in signaling pathways. Mitochondrial and nuclear DNA mutations caused by oxidative damage that impair the oxidative phosphorylation process will result in further mitochondrial ROS production, completing the "vicious cycle" between mitochondria, ROS, genomic instability, and cancer development. The multiple essential roles of mitochondria have been utilized for designing novel mitochondria-targeted anticancer agents. Selective drug delivery to mitochondria helps to increase specificity and reduce toxicity of these agents. In order to reduce mitochondrial ROS production, mitochondria-targeted antioxidants can specifically accumulate in mitochondria by affiliating to a lipophilic penetrating cation and prevent mitochondria from oxidative damage. In consistence with the oncogenic role of ROS, mitochondria targeted antioxidants are found to be effective in cancer prevention and anticancer therapy. A better understanding of the role played by mitochondria in cancer development will help to reveal more therapeutic targets, and will help to increase the activity and selectivity of mitochondria-targeted anticancer drugs. In this review we summarized the impact of mitochondria on cancer and gave summary about the possibilities to target mitochondria for anticancer therapies. J. Cell. Physiol. 231: 2570-2581, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26895994 TI - Ecological divergence and conservatism: spatiotemporal patterns of niche evolution in a genus of livebearing fishes (Poeciliidae: Xiphophorus). AB - BACKGROUND: Ecological factors often have a strong impact on spatiotemporal patterns of biodiversity. The integration of spatial ecology and phylogenetics allows for rigorous tests of whether speciation is associated with niche conservatism (constraints on ecological divergence) or niche divergence. We address this question in a genus of livebearing fishes for which the role of sexual selection in speciation has long been studied, but in which the potential role of ecological divergence during speciation has not been tested. RESULTS: By combining reconstruction of ancestral climate tolerances and disparity indices, we show that the earliest evolutionary split in Xiphophorus was associated with significant divergence for temperature variables. Niche evolution and present day niches were most closely associated with each species' geographic distribution relative to a biogeographic barrier, the Trans-Mexican Volcanic Belt. Tests for similarity of the environmental backgrounds of closely related species suggested that the relative importance of niche conservatism and divergence during speciation varied among the primary clades of Xiphophorus. Closely related species in the two swordtail clades exhibited higher levels of niche overlap than expected given environmental background similarity indicative of niche conservatism. In contrast, almost all species of platyfish had significantly divergent niches compared to environmental backgrounds, which is indicative of niche divergence. CONCLUSION: The results suggest that the relative importance of niche conservatism and divergence differed among the clades of Xiphophorus and that traits associated with niche evolution may be more evolutionarily labile in the platyfishes. Our results ultimately suggest that the taxonomic scale of tests for conservatism and divergence could greatly influence inferences of their relative importance in the speciation process. PMID- 26895997 TI - Hospitalization-Associated Disability in Adults Admitted to a Safety-Net Hospital. PMID- 26895996 TI - [Cystic Fibrosis Cloud database: An information system for storage and management of clinical and microbiological data of cystic fibrosis patients]. AB - The epidemiological and clinical management of cystic fibrosis (CF) patients suffering from acute pulmonary exacerbations or chronic lung infections demands continuous updating of medical and microbiological processes associated with the constant evolution of pathogens during host colonization. In order to monitor the dynamics of these processes, it is essential to have expert systems capable of storing and subsequently extracting the information generated from different studies of the patients and microorganisms isolated from them. In this work we have designed and developed an on-line database based on an information system that allows to store, manage and visualize data from clinical studies and microbiological analysis of bacteria obtained from the respiratory tract of patients suffering from cystic fibrosis. The information system, named Cystic Fibrosis Cloud database is available on the http://servoy.infocomsa.com/cfc_database site and is composed of a main database and a web-based interface, which uses Servoy's product architecture based on Java technology. Although the CFC database system can be implemented as a local program for private use in CF centers, it can also be used, updated and shared by different users who can access the stored information in a systematic, practical and safe manner. The implementation of the CFC database could have a significant impact on the monitoring of respiratory infections, the prevention of exacerbations, the detection of emerging organisms, and the adequacy of control strategies for lung infections in CF patients. PMID- 26895998 TI - Effects of Long-Term Low-Molecular-Weight Heparin on Fractures and Bone Density in Non-Pregnant Adults: A Systematic Review With Meta-Analysis. AB - BACKGROUND: Adults who require long-term anticoagulation with low-molecular weight heparin (LMWH) such as cancer patients or the elderly may be at increased risk of fractures. OBJECTIVE: To determine the effects of LMWH therapy of at least 3 months' duration on fractures and bone mineral density (BMD) in non pregnant adult populations. METHODS: We systematically reviewed electronic databases (e.g., MEDLINE, EMBASE), conferences and bibliographies until June 2015 and included comparative studies in non-pregnant adult populations that examined the effects of LMWH (>=3 months) on fractures and BMD. We synthesized evidence qualitatively and used random-effects meta-analysis to quantify the effect of LMWH on fractures. RESULTS: Sixteen articles reporting 14 studies were included: 10 clinical trials (n = 4865 participants) and four observational cohort studies (3 prospective, n = 221; 1 retrospective, n = 30). BMD and fractures were secondary outcomes in the majority of trials, while they were primary outcomes in the majority of observational studies. In participants with venous thromboembolism and underlying cardiovascular disease or cancer (5 RCTs, n = 2280), LMWH for 3-6 months did not increase the relative risk of all fractures at 6-12 months compared to unfractionated heparin, oral vitamin K antagonists or placebo [pooled risk ratio (RR) = 0.58, 95 % CI: 0.23-1.43; I(2) = 12.5 %]. No statistically significant increase in the risk of fractures at 6-12 months was found for cancer patients (RR = 1.08, 95 % CI: 0.31-3.75; I(2) = 4.4 %). Based on the data from two prospective cohort studies (n = 166), LMWH for 3-24 months decreased mean BMD by 2.8-4.8 % (depending on the BMD site) compared to mean BMD decreases of 1.2-2.5 % with oral vitamin K antagonists. CONCLUSIONS: LMWH for 3-6 months may not increase the risk of fractures, but longer exposure for up to 24 months may adversely affect BMD. Clinicians should consider monitoring BMD in adults on long-term LMWH who are at increased risk of bone loss or fracture. PMID- 26895999 TI - Age and Socioeconomic Gradients of Health of Indian Adults: An Assessment of Self Reported and Biological Measures of Health. AB - This paper describes overall socioeconomic gradients and the age patterns of socioeconomic gradients of health of Indian adults for multiple health indicators encompassing the multiple aspects of health. Cross-sectional data on 11,230 Indians aged 18 years and older from the WHO-SAGE India Wave 1, 2007 were analyzed. Multivariate logit models were estimated to examine effects of socioeconomic status (education and household wealth) and age on four health domains: self-rated health, self-reported functioning, chronic diseases, and biological health measures. Results show that socioeconomic status (SES) was negatively associated with prevalence of each health measure but with considerable heterogeneity across age groups. Results for hypertension and COPD were inconclusive. SES effects are significant while adjusting for background characteristics and health risk factors. The age patterns of SES gradient of health depict divergence with age, however, no conclusive age pattern emerged for biological markers. Overall, results in this paper dispelled the conclusion of negative SES-health association found in some previous Indian studies and reinforced the hypothesis of positive association of SES with health for Indian adults. Higher prevalence of negative health outcomes and SES disparities of health outcomes among older age-groups highlight need for inclusive and focused health care interventions for older adults across socioeconomic spectrum. PMID- 26896001 TI - Improving transparency of scientific reporting to increase value and reduce waste in mental health research. PMID- 26896000 TI - CXCR4-SDF-1 interaction potentially mediates trafficking of circulating tumor cells in primary breast cancer. AB - BACKGROUND: Cytokines are involved in cancer invasion and metastasis. Circulating tumor cells (CTCs) play key role in tumor dissemination and are an independent survival predictor in breast cancer patients. The aim of this study was to assess correlation between CTCs and plasma cytokines in primary breast cancer (PBC) patients. METHODS: This study included 147 chemotherapy naive PBC patients. Peripheral blood mononuclear cells (PBMC) were depleted of hematopoetic cells using RossetteSepTM negative selection kit. RNA extracted from CD45-depleted PBMC was interrogated for expression of EMT (Twist1, Snail1, Slug, Zeb1) and epithelial (Ck19) gene transcripts by qRT-PCR. The concentrations of 51 plasma cytokines were measured using multiplex bead arrays. RESULTS: CTCs were detected in 25.2% patients. CTCs exhibiting only epithelial markers (CTC_EP) and only EMT markers (CTC_EMT) were present evenly in 11.6% patients, while CTCs co-expressing both markers were detected in 2.0% patients. Patients with presence of CTC_EP in peripheral blood had significantly elevated levels of plasma IFN-alpha2, IL-3, MCP-3, beta-NGF, SCF, SCGF-beta, TNF-beta and SDF-1 compared to patients without CTC_EP. CTC_EP exhibited overexpression of SDF-1 receptor and CXCR4, but not other corresponding cytokine receptor, and in multivariate analysis SDF-1 was independently associated with CTC_EP. There was an inverse correlation between CTC_EMT and plasma cytokines CTACK, beta-NGF and TRAIL, while presence of either subtype of CTCs was associated with increased level of TGF-beta2. CONCLUSION: Using cytokine profiling, we identified cytokines associated with CTCs subpopulations in peripheral blood of PBC. Our data suggest that CXCR4-SDF-1 axis is involved in mobilization and trafficking of epithelial CTCs. PMID- 26896003 TI - Short-term landfill methane emissions dependency on wind. AB - Short-term (2-10h) variations of whole-landfill methane emissions have been observed in recent field studies using the tracer dilution method for emissions measurement. To investigate the cause of these variations, the tracer dilution method is applied using 1-min emissions measurements at Sandtown Landfill (Delaware, USA) for a 2-h measurement period. An atmospheric dispersion model is developed for this field test site, which is the first application of such modeling to evaluate atmospheric effects on gas plume transport from landfills. The model is used to examine three possible causes of observed temporal emissions variability: temporal variability of surface wind speed affecting whole landfill emissions, spatial variability of emissions due to local wind speed variations, and misaligned tracer gas release and methane emissions locations. At this site, atmospheric modeling indicates that variation in tracer dilution method emissions measurements may be caused by whole-landfill emissions variation with wind speed. Field data collected over the time period of the atmospheric model simulations corroborate this result: methane emissions are correlated with wind speed on the landfill surface with R(2)=0.51 for data 2.5m above ground, or R(2)=0.55 using data 85m above ground, with emissions increasing by up to a factor of 2 for an approximately 30% increase in wind speed. Although the atmospheric modeling and field test are conducted at a single landfill, the results suggest that wind induced emissions may affect tracer dilution method emissions measurements at other landfills. PMID- 26896004 TI - Fluidized bed gasification of industrial solid recovered fuels. AB - The study evaluates the technical feasibility of the fluidized bed gasification of three solid recovered fuels (SRFs), obtained as co-products of a recycling process. The SRFs were pelletized and fed to a pilot scale bubbling fluidized bed reactor, operated in gasification and co-gasification mode. The tests were carried out under conditions of thermal and chemical steady state, with a bed of olivine particles and at different values of equivalence ratio. The results provide a complete syngas characterization, in terms of its heating value and composition (including tars, particulates, and acid/basic pollutants) and of the chemical and physical characterization of bed material and entrained fines collected at the cyclone outlet. The feasibility of the fluidized bed gasification process of the different SRFs was evaluated with the support of a material and substance flow analysis, and a feedstock energy analysis. The results confirm the flexibility of fluidized bed reactor, which makes it one of the preferable technologies for the gasification of different kind of wastes, even in co-gasification mode. The fluidized bed gasification process of the tested SRFs appears technically feasible, yielding a syngas of valuable quality for energy applications in an appropriate plant configuration. PMID- 26896006 TI - Humanism, compassion and the call to caring. PMID- 26896002 TI - Synchrotron Infrared and Deep UV Fluorescent Microspectroscopy Study of PB1-F2 beta-Aggregated Structures in Influenza A Virus-infected Cells. AB - PB1-F2 is a virulence factor of influenza A virus (IAV) whose functions remain misunderstood. The different roles of PB1-F2 may be linked to its structural polymorphism and to its propensity to assemble into oligomers and amyloid fibers in the vicinity of the membrane of IAV-infected cells. Here, we monitored the impact of PB1-F2 on the biochemical composition and protein structures of human epithelial pulmonary cells (A549) and monocytic cells (U937) upon IAV infection using synchrotron Fourier-transform infrared (FTIR) and deep UV (DUV) microscopies at the single-cell level. Cells were infected with a wild-type IAV and its PB1-F2 knock-out mutant for analyses at different times post-infection. IR spectra were recorded in each condition and processed to evaluate the change in the component band of the spectra corresponding to the amide I (secondary structure) and the CH stretching region (membrane). The IR spectra analysis revealed that expression of PB1-F2 in U937 cells, but not in A549 cells, results in the presence of a specific beta-aggregate signature. Furthermore, the lipid membrane composition of U937 cells expressing PB1-F2 was also altered in a cell type-dependent manner. Using DUV microscopy and taking advantage of the high content of tryptophan residues in the sequence of PB1-F2 (5/90 aa), we showed that the increase of the autofluorescent signal recorded in monocytic cells could be correlated with the IR detection of beta-aggregates. Altogether, our results constitute an important step forward in the understanding of the cell type dependent function of PB1-F2. PMID- 26896007 TI - Revisiting 'Performance rating scale for peer and self assessment'. PMID- 26896008 TI - Humanism and other acts of faith. PMID- 26896009 TI - Mapping the landscape or exploring the terrain? Progressing humanism in medical education. PMID- 26896010 TI - Bench to bedside: medical humanities education and assessment as a translational challenge. PMID- 26896011 TI - Exploring the interstitial space between the ideal and the practised: humanism and the hidden curriculum of system reform. PMID- 26896012 TI - Nurturing empathy and compassion: what might the neurosciences have to offer? PMID- 26896013 TI - When I say... equity. PMID- 26896014 TI - Rethinking research in the medical humanities: a scoping review and narrative synthesis of quantitative outcome studies. AB - OBJECTIVES: The rise of medical humanities teaching in medical education has introduced pressure to prove efficacy and utility. Review articles on the available evidence have been criticised for poor methodology and unwarranted conclusions. To support a more nuanced discussion of how the medical humanities work, we conducted a scoping review of quantitative studies of medical humanities teaching. METHODS: Using a search strategy involving MEDLINE, EMBASE and ERIC, and hand searching, our scoping review located 11 045 articles that referred to the use of medical humanities teaching in medical education. Of these, 62 studies using quantitative evaluation methods were selected for review. Three iterations of analysis were performed: descriptive, conceptual, and discursive. RESULTS: Descriptive analysis revealed that the medical humanities as a whole cannot be easily systematised based on simple descriptive categories. Conceptual analysis supported the development of a conceptual framework in which the foci of the arts and humanities in medical education can be mapped alongside their related epistemic functions for teaching and learning. Within the framework, art functioned as expertise, as dialogue or as a means of expression and transformation. In the discursive analysis, we found three main ways in which the relationship between the arts and humanities and medicine was constructed as, respectively, intrinsic, additive and curative. CONCLUSIONS: This review offers a nuanced framework of how different types of medical humanities work. The epistemological assumptions and discursive positioning of medical humanities teaching frame the forms of outcomes research that are considered relevant to curriculum decision making, and shed light on why dominant review methodologies make some functions of medical humanities teaching visible and render others invisible. We recommend the use of this framework to improve the rigor and relevance of future explorations of the efficacy and utility of medical humanities teaching. PMID- 26896016 TI - A review of creative and expressive writing as a pedagogical tool in medical education. AB - CONTEXT: The act of writing offers an opportunity to foster self-expression and organisational abilities, along with observation and descriptive skills. These soft skills are relevant to clinical thinking and medical practice. Medical school curricula employ pedagogical approaches suitable for assessing medical and clinical knowledge, but teaching methods for soft skills in critical thinking, listening and verbal expression, which are important in patient communication and engagement, may be less formal. Creative and expressive writing that is incorporated into medical school courses or clerkships offers a vehicle for medical students to develop soft skills. The aim of this review was to explore creative and expressive writing as a pedagogical tool in medical schools in relation to outcomes of medical education. METHODS: This project employed a scoping review approach to gather, evaluate and synthesise reports on the use of creative and expressive writing in US medical education. Ten databases were searched for scholarly articles reporting on creative or expressive writing during medical school. Limitation of the results to activities associated with US medical schools, produced 91 articles. A thematic analysis of the articles was conducted to identify how writing was incorporated into the curriculum. RESULTS: Enthusiasm for writing as a pedagogical tool was identified in 28 editorials and overviews. Quasi-experimental, mixed methods and qualitative studies, primarily writing activities, were aimed at helping students cognitively or emotionally process difficult challenges in medical education, develop a personal identity or reflect on interpersonal skills. The programmes and interventions using creative or expressive writing were largely associated with elective courses or clerkships, and not required courses. CONCLUSIONS: Writing was identified as a potentially relevant pedagogical tool, but not included as an essential component of medical school curricula. PMID- 26896017 TI - A guiding framework to maximise the power of the arts in medical education: a systematic review and metasynthesis. AB - CONTEXT: A rich literature describes many innovative uses of the arts in professional education. However, arts-based teaching tends to be idiosyncratic, depending on the interests and enthusiasm of individual teachers, rather than on strategic design decisions. An overarching framework is needed to guide implementation of arts-based teaching in medical education. The objective of this study was to review and synthesise the literature on arts-based education and provide a conceptual model to guide design, evaluation and research of the use of the arts in medical education. METHODS: A systematic literature review using the PubMed and ERIC databases. Search terms included humanism, art, music, literature, teaching, education, learning processes, pedagogy and curriculum. We selected empirical studies and conceptual articles about the use of creative arts, imagery and symbolism in the context of professional education. Data synthesis involved a qualitative content analysis of 49 included articles, identifying themes related to educational characteristics, processes and outcomes in arts-based education. RESULTS: Four common themes were identified describing (i) unique qualities of the arts that promote learning, (ii) particular ways learners engage with art, (iii) documented short- and long-term learning outcomes arising from arts-based teaching and (iv) specific pedagogical considerations for using the arts to teach in professional education contexts. CONCLUSIONS: The arts have unique qualities that can help create novel ways to engage learners. These novel ways of engagement can foster learners' ability to discover and create new meanings about a variety of topics, which in turn can lead to better medical practice. At each of these steps, specific actions by the teacher can enhance the potential for learners to move to the next step. The process can be enhanced when learners participate in the context of a group, and the group itself can undergo transformative change. Future work should focus on using this model to guide process design and outcome measurement in arts-based education. PMID- 26896018 TI - A social neuroscience-informed model for teaching and practising compassion in health care. AB - CONTEXT: Empathy and compassion are important catalysts for the healing process, but some research suggests their decline during training and practice. Compassion involves recognition, understanding, emotional resonance and empathic concern for another's concerns, distress, pain and suffering, coupled with their acknowledgement, and motivation and relational action to ameliorate these conditions. COMPASSION, ALTRUISM AND REWARD: Neuroscientists have identified neural networks that generate shared representations of directly experienced and observed feelings, sensations and actions. When shared representations evoke empathic concern or compassion for another's painful situation, humans experience altruistic motivation to help. The resulting behaviours are associated with activation of areas in the brain associated with affiliation and reward. COMPASSION MODULATORS: Activation of these neural networks is sensitive to multiple inter- and intrapersonal influences. These include the ability to focus one's attention, the ability to receive and accurately interpret input about distress, the perspective one adopts in order to understand another's experience, self-other boundary awareness, the degree to which one values another's welfare, the ability to recognise and regulate one's own emotions, the ability to attend to one's own wellbeing through self-care and self-compassion, effective communication skills, reflection and meta-cognition. CONCLUSIONS: Current research suggests that compassion can be modulated through education and training and is associated with positive emotions, a sense of affiliation, reward and prosocial behaviours. A compassion process model and framework with examples of educational goals, interventions and resources for curriculum development are described. However, education must be aligned with changes in clinical practice to sustain compassionate care. PMID- 26896015 TI - Assessing empathy development in medical education: a systematic review. AB - CONTEXT: Empathy in doctor-patient relationships is a familiar topic for medical scholars and a crucial goal for medical educators. Nonetheless, there are persistent disagreements in the research literature concerning how best to evaluate empathy among physicians, and whether empathy declines or increases across medical education. Some researchers have argued that the instruments used to study 'empathy' may not measure anything meaningful to clinical practice or patient satisfaction. METHODS: We performed a systematic review to learn how empathy is conceptualised in medical education research. We examined how researchers define the central construct of empathy and what they choose to measure, and investigated how well definitions and operationalisations match. RESULTS: Among the 109 studies that met our search criteria, 20% failed to define the central construct of empathy at all and only 13% used an operationalisation that was well matched to the definition provided. The majority of studies were characterised by internal inconsistencies and vagueness in both the conceptualisation and operationalisation of empathy, constraining the validity and usefulness of the research. The methods most commonly used to measure empathy relied heavily on self-report and cognition divorced from action, and may therefore have limited power to predict the presence or absence of empathy in clinical settings. Finally, the large majority of studies treated empathy itself as a 'black box', using global construct measurements that are unable to shed light on the underlying processes that produce an empathic response. CONCLUSIONS: We suggest that future research should follow the lead of basic scientific research that conceptualises empathy as relational - an engagement between a subject and an object - rather than as a personal quality that may be modified wholesale through appropriate training. PMID- 26896019 TI - The effects of power, leadership and psychological safety on resident event reporting. AB - CONTEXT: Although the reporting of adverse events is a necessary first step in identifying and addressing lapses in patient safety, such events are under reported, especially by frontline providers such as resident physicians. OBJECTIVES: This study describes and tests relationships between power distance and leader inclusiveness on psychological safety and the willingness of residents to report adverse events. METHODS: A total of 106 resident physicians from the departments of neurosurgery, orthopaedic surgery, emergency medicine, otolaryngology, neurology, obstetrics and gynaecology, paediatrics and general surgery in a mid-Atlantic teaching hospital were asked to complete a survey on psychological safety, perceived power distance, leader inclusiveness and intention to report adverse events. RESULTS: Perceived power distance (beta = 0.26, standard error [SE] 0.06, 95% confidence interval [CI] -0.37 to 0.15; p < 0.001) and leader inclusiveness (beta = 0.51; SE 0.07, 95% CI 0.38-0.65; p < 0.001) both significantly predicted psychological safety, which, in turn, significantly predicted intention to report adverse events (beta = 0.34; SE 0.08, 95% CI 0.18-0.49; p < 0.001). Psychological safety significantly mediated the direct relationship between power distance and intention to report adverse events (indirect effect: -0.09; SE 0.02, 95% CI -0.13 to 0.04; p < 0.001). Psychological safety also significantly mediated the direct relationship between leader inclusiveness and intention to report adverse events (indirect effect: 0.17; SE 0.02, 95% CI 0.08-0.27; p = 0.001). CONCLUSIONS: Psychological safety was found to be a predictor of intention to report adverse events. Perceived power distance and leader inclusiveness both influenced the reporting of adverse events through the concept of psychological safety. Because adverse event reporting is shaped by relationships and culture external to the individual, it should be viewed as an organisational as much as a personal function. Supervisors and other leaders in health care should ensure that policies, procedures and leadership practices build psychological safety and minimise power distance between low- and high status members in order to support greater reporting of adverse events. PMID- 26896020 TI - Do OSCE progress test scores predict performance in a national high-stakes examination? AB - CONTEXT: Progress tests, in which learners are repeatedly assessed on equivalent content at different times in their training and provided with feedback, would seem to lend themselves well to a competency-based framework, which requires more frequent formative assessments. The objective structured clinical examination (OSCE) progress test is a relatively new form of assessment that is used to assess the progression of clinical skills. The purpose of this study was to establish further evidence for the use of an OSCE progress test by demonstrating an association between scores from this assessment method and those from a national high-stakes examination. METHODS: The results of 8 years' of data from an Internal Medicine Residency OSCE (IM-OSCE) progress test were compared with scores on the Royal College of Physicians and Surgeons of Canada Comprehensive Objective Examination in Internal Medicine (RCPSC IM examination), which is comprised of both a written and performance-based component (n = 180). Correlations between scores in the two examinations were calculated. Logistic regression analyses were performed comparing IM-OSCE progress test scores with an 'elevated risk of failure' on either component of the RCPSC IM examination. RESULTS: Correlations between scores from the IM-OSCE (for PGY-1 residents to PGY 4 residents) and those from the RCPSC IM examination ranged from 0.316 (p = 0.001) to 0.554 (<.001) for the performance-based component and 0.305 (p = 0.002) to 0.516 (p < 0.001) for the written component. Logistic regression models demonstrated that PGY-2 and PGY-4 scores from the IM-OSCE were predictive of an 'elevated risk of failure' on both components of the RCPSC IM examination. CONCLUSIONS: This study provides further evidence for the use of OSCE progress testing by demonstrating a correlation between scores from an OSCE progress test and a national high-stakes examination. Furthermore, there is evidence that OSCE progress test scores are predictive of future performance on a national high stakes examination. PMID- 26896021 TI - Limits of 'patient-centredness': valuing contextually specific communication patterns. AB - CONTEXT: Globally, doctor-patient communication is becoming synonymous with high quality health care in the 21st century. However, what is meant by 'good communication' and whether there is consensus internationally remain unclear. OBJECTIVES: Here, we characterise understandings of 'good communication' in future doctors from medical schools in three contextually contrasting continents. Given locally specific socio-cultural influences, we hypothesised that there would be a lack of global consensus on what constitutes 'good communication'. METHODS: A standardised two-phase methodology was applied in turn to each of three medical schools in the UK, Egypt and India (n = 107 subjects), respectively, in which students were asked: 'What is good communication?' Phase I involved exploratory focus groups to define preliminary themes (mean number of participants per site: 17). Phase II involved thematic confirmation and expansion in one-to-one semi-structured interviews (mean number of participants per site: 18; mean hours of dialogue captured per site: 55). Findings were triangulated and analysed using grounded theory. RESULTS: The overarching theme that emerged from medical students was that 'good communication' requires adherence to certain 'rules of communication'. A shared rule that doctors must communicate effectively despite perceived disempowerment emerged across all sites. However, contradictory culturally specific rules about communication were identified in relation to three major domains: family; gender, and emotional expression. Egyptian students perceived emotional aspects of Western doctors' communication strikingly negatively, viewing these doctors as problematically cold and unresponsive. CONCLUSIONS: Contradictory perceptions of 'good communication' in future doctors are found cross-continentally and may contribute to prevalent cultural misunderstandings in medicine. The lack of global consensus on what defines good communication challenges prescriptively taught Western 'patient-centredness' and questions assumptions about international transferability. Health care professionals must be educated openly about flexible, context-specific communication patterns so that they can avoid cultural incompetence and tailor behaviours in ways that optimise therapeutic outcomes wherever they work around the globe. PMID- 26896023 TI - Corrigendum. PMID- 26896022 TI - Barriers to hospitalist fellow interactions. PMID- 26896026 TI - Mental illness in Saudi Arabia: Stigma and acceptability. PMID- 26896024 TI - Project ACHIEVE - using implementation research to guide the evaluation of transitional care effectiveness. AB - BACKGROUND: Poorly managed hospital discharges and care transitions between health care facilities can cause poor outcomes for both patients and their caregivers. Unfortunately, the usual approach to health care delivery does not support continuity and coordination across the settings of hospital, doctors' offices, home or nursing homes. Though complex efforts with multiple components can improve patient outcomes and reduce 30-day readmissions, research has not identified which components are necessary. Also we do not know how delivery of core components may need to be adjusted based on patient, caregiver, setting or characteristics of the community, or how system redesign can be accelerated. METHODS/DESIGN: Project ACHIEVE focuses on diverse Medicare populations such as individuals with multiple chronic diseases, patients with low health literacy/numeracy and limited English proficiency, racial and ethnic minority groups, low-income groups, residents of rural areas, and individuals with disabilities. During the first phase, we will use focus groups to identify the transitional care outcomes and components that matter most to patients and caregivers to inform development and validation of assessment instruments. During the second phase, we will evaluate the comparative effectiveness of multi component care transitions programs occurring across the U.S. Using a mixed methods approach for this evaluation, we will study historical (retrospective) and current and future (prospective) groups of patients, caregivers and providers using site visits, surveys, and clinical and claims data. In this natural experiment observational study, we use a fractional factorial study design to specify comparators and estimate the individual and combined effects of key transitional care components. DISCUSSION: Our study will determine which evidence based transitional care components and/or clusters most effectively produce patient and caregiver desired outcomes overall and among diverse patient and caregiver populations in different healthcare settings. Using the results, we will develop concrete, actionable recommendations regarding how best to implement these strategies. Finally, this work will provide tools for hospitals, community based organizations, patients, caregivers, clinicians and other stakeholders to help them make informed decisions about which strategies are most effective and how best to implement them in their communities. TRIAL REGISTRATION: Registered as NCT02354482 on clinicaltrials.gov on 1/29/2015. PMID- 26896025 TI - Preoperative prediction of cerebral hyperperfusion after carotid endarterectomy using middle cerebral artery signal intensity in 1.5-tesla magnetic resonance angiography followed by cerebrovascular reactivity to acetazolamide using brain perfusion single-photon emission computed tomography. AB - OBJECTIVE: The purpose of the present study was to determine whether the signal intensity of the middle cerebral artery (MCA) on preoperative 1.5-T magnetic resonance angiography (MRA) could identify patients at risk for hyperperfusion following carotid endarterectomy (CEA) as a clinical screening test and whether an additional measurement of preoperative cerebrovascular reactivity (CVR) to acetazolamide on brain perfusion single-photon emission computed tomography (SPECT) could increase the predictive accuracy for the development of hyperperfusion. METHODS: In 301 patients, the signal intensity of the MCA ipsilateral to CEA on MRA was preoperatively graded according to the ability to visualize the MCA. For patients with reduced MCA signal intensity on the MRA study, CVR to acetazolamide was subsequently assessed using brain perfusion SPECT. Cerebral hyperperfusion was determined intraoperatively using transcranial regional cerebral oxygen saturation monitoring with near-infrared spectroscopy. RESULTS: Preoperative reduced MCA signal intensity was significantly associated with the development of cerebral hyperperfusion (95% CI, 1.188-3.965; p = 0.0352). While the sensitivity and negative predictive value were 100% both for the preoperative MCA signal intensity alone and in combination with subsequent preoperative CVR to acetazolamide, the specificity and positive predictive value were significantly greater for the latter than for the former (p < 0.05). CONCLUSIONS: Signal intensity of the MCA on preoperative 1.5-T MRA identifies patients at risk for hyperperfusion following CEA as a clinical screening test. An additional measurement of preoperative CVR to acetazolamide increases the predictive accuracy for the development of hyperperfusion. PMID- 26896028 TI - Do people with bipolar disorders have access to psychosocial treatments? A survey in Italy. AB - BACKGROUND: Several guidelines consider psychosocial treatments an essential component of clinical management of bipolar disorders in addition to drug therapy. However, to what extent such interventions are available in everyday practice to the average patient attending mental health services is not known. AIMS: This study aims to investigate access of people with bipolar disorders to psychosocial treatments in a community-based care system. METHOD: Information on care delivery and service utilization were retrieved from the psychiatric database of Lombardy, Italy, covering a population of 9,743,000, for all adults who had at least one contact in 2009 with psychiatric services. Rates of patients with a diagnosis of bipolar disorder who had access to individual psychotherapy, couple/family therapy, group psychotherapy and family interventions were calculated and compared to patients with schizophrenia and depression. RESULTS: A total of 8,899 subjects with bipolar disorder had been in contact with psychiatric services, corresponding to a treated annual prevalence rate of 1.10/00. More than 80% of patients were treated in community settings. Rates of patients receiving structured psychosocial treatments ranged from 0.7% for couple/family therapy to 6.1% for individual psychotherapy. No differences with patients with schizophrenia and depression were found. Patients with schizophrenia received more interventions labeled as rehabilitation. CONCLUSION: Few people with bipolar disorders had access to psychosocial treatments. Even in a well-developed system of community care, offer of psychosocial interventions for bipolar disorders is inadequate. This issue should be a target for future research on dissemination and implementation strategies. PMID- 26896027 TI - Perceived insecurity, mental health and urbanization: Results from a multicentric study. AB - AIMS: This article aims to (1) explore the levels of perceived insecurity in a sample of patients with mood or anxiety disorders and (2) assess whether living in 'big cities' can influence the levels of patients' perceived insecurity and social contacts compared to living in a non-urbanized context. METHODS: A total of 24 Italian mental health centers (MHCs) have been invited to participate. Twenty patients consecutively accessing the MHC have been recruited. All patients have been assessed using validated assessment tools. RESULTS: The sample consisted of 426 patients, mostly female, with a mean age of 45 years. Globally, 52.2% of patients had a diagnosis of mood disorders, and 37.8% had anxiety disorders. Half of the sample declared that the main feeling toward life is uncertainty; higher levels of pessimistic views toward life have been detected in patients living in urban areas. A positive association between negative attitudes toward life and higher levels of depressive and anxiety symptoms, poor social functioning and higher levels of perceived psychological distress has been found. CONCLUSION: Our findings confirm the presence of a common sense of perceived uncertainty among our sample. Such attitude toward life can have a detrimental impact on patients' psychological and physical well-being, contributing to high levels of distress. PMID- 26896029 TI - Characteristics of suicidal outpatients with mood, anxiety and somatoform disorders: The role of childhood abuse and neglect. AB - BACKGROUND: The most prevalent psychiatric disorders are mood, anxiety and somatoform (MAS) disorders which show high mutual comorbidity, childhood trauma and elevated risk of suicidality. So far, no studies have compared suicide risk in a secondary care population with comorbid MAS disorders. This gap was taken as starting point for the study. AIMS: In comparing suicidal and non-suicidal MAS patients, the following was examined: suicide risk in the three disorder groups, socio-demographic and clinical characteristics, occurrence of childhood trauma types and contribution of childhood trauma to suicidality. METHODS: This cross sectional study compared suicidal (n = 316) versus non-suicidal comorbid MAS outpatients (n = 929) by means of the Mini-International Neuropsychiatric Interview Plus (MINI-Plus), Brief Symptom Inventory (BSI), Short Form Health Survey 36 (SF-36), Dimensional Assessment of Personality Pathology-Short Form (DAPP-SF) and Childhood Trauma Questionnaire (CTQ). RESULTS: Compared to non suicidal MAS patients, suicidal MAS patients mostly had mood disorders (single/comorbid), multiple diagnoses, worse functioning, more personality pathology (self-harm) and more childhood neglect and abuse. CONCLUSION: Especially (comorbid) depressed patients are at risk for suicide, and routine screening and monitoring of childhood trauma and suicidality in them are recommended, along with the timely deployment of appropriate trauma-focused psychotherapy. PMID- 26896030 TI - Exploring communication of traumatic experiences from Khmer Rouge genocide survivors to their offspring: In-depth interviews with both generations. AB - BACKGROUND: Traumatic events experienced by parents who have survived genocide influence mental health among their offspring. This study aims at exploring how the communication of traumatic events between Khmer Rouge survivors and their offspring was perceived by both generations. METHODS: Qualitative interviews were performed with six Khmer Rouge survivors and with six young people representing the second generation and were analysed using a content analysis approach. DISCUSSION: Parents felt that informing their children was important to instill gratitude for living a better life and to empower them. Among children, this was met with empathy but sometimes also disbelief and at times they blamed their parents for being too submissive. CONCLUSION: The study discloses the complexity, pros and cons of intergenerational sharing of trauma. PMID- 26896031 TI - [Criterion and Construct Validity in Nursing Diagnosis "Sedentary Lifestyle" in People over 50 Years Old]. AB - OBJECTIVE: The aim of the study is to identify the construct and criterion validity of the nursing diagnosis label Sedentary Lifestyle. METHODS: A cross sectional study in a nursing consultation in primary health care was conducted. Participants were all people that was attended for one year over 50 who voluntarily wish to participate (n=85) in the study. Objective weekly physical activity was measured in METs with an Accelerometer, objective measure of performance was measured by gait speed EPESE Battery (both measures that were used as the gold standard), and physical activity questionnaires (RAPA), the COOP WONCA physical fitness chart. Spearman correlation coefficients, mean comparison tests and analysis of sensitivity and specificity were used as statistical analysis. RESULTS: The diagnosis "Sedentary Lifestyle" showed a positive correlation between its manifestations and physical activity measured in METs (r=0.39) and EPESE gait speed (r=0.35). The diagnosis showed a sensitivity of 85.1% and a specificity of 65.2% and showed ability to discriminate active people from those that are not using METs as a measure of physical activity (t=-4.4). CONCLUSIONS: The diagnosis "Sedentary Lifestyle" shows criterion and construct validity. PMID- 26896032 TI - Comparative Study of Autoantibody Responses between Lung Adenocarcinoma and Benign Pulmonary Nodules. AB - INTRODUCTION: The reduction in lung cancer mortality associated with computed tomography (CT) screening has led to its increased use and a concomitant increase in the detection of benign pulmonary nodules. Many individuals found to have benign nodules undergo unnecessary, costly, and invasive procedures. Therefore, there is a need for companion diagnostics that stratify individuals with pulmonary nodules into high-risk or low-risk groups. Lung cancers can trigger host immune responses and elicit antibodies against tumor antigens. The identification of these autoantibodies (AAbs) and their corresponding antigens may expand our knowledge of cancer immunity, leading to early diagnosis or even benefiting immunotherapy. Previous studies were performed mostly in the context of comparing cancers and healthy (smoker) controls. We have performed one of the first studies to understand humoral immune response in patients with cancer, patients with benign nodules, and healthy smokers. METHODS: We first profiled seroreactivity to 10,000 full-length human proteins in 40 patients with early stage lung cancer and 40 smoker controls by using nucleic acid programmable protein arrays to identify candidate cancer-specific AAbs. Enzyme-linked immunosorbent assays of promising candidates were performed on 137 patients with lung cancer and 127 smoker controls, as well as on 170 subjects with benign pulmonary nodules. RESULTS: From protein microarray screening experiments using a discovery set of 40 patients and 40 smoker controls, 17 antigens showing higher reactivity in lung cancer cases relative to the controls were subsequently selected for evaluation in a large sample set (n = 264) by using enzyme-linked immunosorbent assay. A five-AAb classifier (tetratricopeptide repeat domain 14 [TTC14], B-Raf proto-oncogene, serine/threonine kinase [BRAF], actin like 6B [ACTL6B], MORC family CW-type zinc finger 2 [MORC2], and cancer/testis antigen 1B [CTAG1B]) that can differentiate lung cancers from smoker controls with a sensitivity of 30% at 89% specificity was developed. We further tested AAb responses in subjects with CT-positive benign nodules (n = 170), and developed a five-AAb panel (keratin 8, type II, TTC14, Kruppel-like factor 8, BRAF, and tousled like kinase 1) with a sensitivity of 30% at 88% specificity. Interestingly, messenger RNA levels of six AAb targets (TTC14, BRAF, MORC family CW-type zinc finger 2, cancer/testis antigen 1B, keratin 8, type II, and tousled like kinase 1) were also found to increase in lung adenocarcinoma tissues based on The Cancer Genome Atlas data set. CONCLUSION: We discovered AAbs associated with lung adenocaricnoma that have the potential to differentiate cancer from CT positive benign diseases. We believe that these antibodies warrant future validation using a larger sample set and/or longitudinal samples individually or as a panel. They could potentially be part of companion molecular diagnostic modalities that will benefit subjects undergoing CT screening for lung cancer. PMID- 26896035 TI - Validity of Commonly Used Clinical Tests to Diagnose and Screen for Spinal Pain in Adolescents: A School-Based Cohort Study in 1300 Danes Aged 11-15 Years. AB - OBJECTIVE: The overall aim of this study was to determine the ability of 2 selected clinical tests to detect or predict neck pain, mid back pain, and low back pain in a school-based cohort of Danish 11- to 15-year-olds. METHODS: A school-based 2-year prospective cohort study was conducted. Data were collected at the age of 11 to 13 (n = 1224) and 2 years later (n = 963). Spinal pain (neck pain, mid back pain, and low back pain) was assessed by an electronic survey completed during school time, and reference standard was defined as both lifetime prevalence and frequent pain as a proxy of severity. The tests included assessments of scoliosis, hypermobility, global mobility, intersegmental mobility, end range pain, and isometric endurance of back extensors. Sensitivity, specificity, negative and positive predictive values, and odds ratios were calculated for each test individually, and area under the receiver operating characteristic curve was calculated for evaluation of all tests combined. RESULTS: The sensitivity was low, and specificity was high for all tests at both baseline (age, 11-13 years) and follow-up (age, 13-15 years). When all tests were evaluated collectively in 1 model, the area under the receiver operating characteristic curve ranged from 0.60 to 0.65. None of the selected tests could predict incidence cases of neck pain, mid back pain, or low back pain. CONCLUSION: Clinical tests commonly used in spinal screening in adolescents could not detect present spinal pain or predict future spinal pain. However, some statistically significant associations between spinal pain and tests involving a pain response from the participant were found. PMID- 26896037 TI - Race/Sex Interactions and HIV Testing Among College Students. AB - OBJECTIVES: The primary aim of the study was to examine race/sex interactions and other behavioral and demographic covariates of past-year HIV testing among college students attending a racially diverse historically black university. The relationship between race/sex interactions and engaging with multiple sex partners during the past year was also examined. PARTICIPANTS: The sample included 566 students who identified as Black or White and engaged in vaginal, oral, or anal sex during the past 12 months. METHODS: A total of 113 undergraduate classes were randomly selected, stratified by time of day. Surveys were administered by project team members who were assisted by peer health educators to increase the cultural competency of the study. The response rate was 94 %. RESULTS: The sample of 566 participants included Black women (54 %), Black men (26 %), White women (13 %), and White men (7 %). The mean age was 25 (median = 22 years), and 42 % resided on campus. Nearly half (46 %) reported two or more sex partners in the past year, and 9 % of participants were diagnosed with STD in the past year. Sixty-nine percent reported being tested for HIV, 58 % had been tested in the past year, and 18 % had been tested for HIV on two or more occasions during the past year. In multivariable analysis, Black men (AOR = 0.43; 95 % CI = 0.27, 0.69), White women (AOR = 0.25; 95 % CI = 0.14, 0.47), and White men (AOR = 0.22; 95 % CI = 0.10, 0.49) were significantly less likely than Black women to be tested for HIV in the past year. Residing off campus (AOR = 1.88; 95 % CI = 1.18, 2.99) and engaging with two or more sex partners in the past year (AOR = 2.59; 95 % CI = 1.70, 3.95) significantly increased the likelihood of HIV testing in the past year. Students who engaged only with heterosexual partners (AOR = .25; 95 % CI = 0.09, 0.76) or were female and bisexual (AOR = 0.17; 95 % CI = 0.04, 0.69) were less likely to be tested for HIV in the past year compared to men who have sex with men/men and women. In a separate model, Black men (AOR = 1.87; 95 % CI = 1.18, 2.97) were significantly more likely than Black women to engage with two or more sex partners during the previous year. Compared to Black women, White women (AOR = 0.51; 95 % CI = 0.26, 0.98) were less likely to report two or more sex partners in the past year. Students involved in a relationship during the past 30 days (AOR = 0.33; 95 % CI = 0.22, 0.49) were less likely than other students to engage with two or more sex partners in the past year. CONCLUSIONS: Over half (58 %) of the students had been tested for HIV in the past year-a promising outcome. However, 42 % of sexually active students had not been tested. Campus prevention initiatives need to reinforce the importance of frequent HIV testing. In particular, targeted prevention efforts need to be focused on heterosexual Black male college students. PMID- 26896036 TI - Psychological Outcomes After a False Positive Mammogram: Preliminary Evidence for Ethnic Differences Across Time. AB - Adverse psychological consequences of screening mammography are well-documented for women who receive a false positive result. However, little is known about ethnic differences. To address this gap, we examine distress associated with an abnormal mammogram (results-related distress) and perceived lifetime risk of breast cancer (perceived risk) among Latinas and non-Latina White (NLW) women 3 months after receipt of a false positive result. A sample of 28 Latina and 27 NLW women who received an initial abnormal mammogram result and later, a definitive non-cancer diagnosis were recruited for this descriptive, longitudinal study. Women were interviewed twice: within 30 days and 3 months after a false positive result. Questionnaires included standard sociodemographic questions, the Impact of Events Scale-Revised, and two perceived breast cancer risk items. All participants experienced decreased distress 3 months after the initial results. Latinas experienced higher levels of distress, F(1,45) = 4.58, p = 0.04, and had a significant increase in perceived breast cancer risk over time, F(1,45) = 3.99, p = 0.05. Larger population-based studies are necessary to confirm ethnic differences in mental health consequences of false positive results. Given cultural emphases concerning respect for authority figures, healthcare professionals may be particularly helpful in working with Latinas to mitigate distress and clarify accurate perceptions of breast cancer risk through evidence based practice. PMID- 26896038 TI - Left ventricular wall thickness in patients with hypertrophic cardiomyopathy: a comparison between cardiac magnetic resonance imaging and echocardiography. AB - We assessed whether cardiac MRI (CMR) and echocardiography (echo) have significant differences measuring left ventricular (LV) wall thickness (WT) in hypertrophic cardiomyopathy (HCM) as performed in the clinical routine. Retrospectively identified, clinically diagnosed HCM patients with interventricular-septal (IVS) pattern hypertrophy who underwent CMR and echo within the same day were included. Left Ventricular WT was measured by CMR in two planes and compared to both echo and contrast echo (cecho). 72 subjects, mean age 50.7 +/- 16.2 years, 68 % males. Interventricular septal WT by echo and CMR planes showed good to excellent correlation. However, measurements of the postero lateral wall showed poor correlation. Bland-Altman plots showed greater maximal IVS WT by echo compared to CMR measurement [SAX = 1.7 mm (-5.8, 9.3); LVOT = 1.1 mm (-5.6, 7.8)]. Differences were smaller between cecho and CMR [SAX = 0.8 mm ( 9.2, 10.8); LVOT = -0.2 mm (-10.0, 9.6)]. Severity of WT by quartiles showed greater differences between echo and SAX CMR WT compared to cecho. Echocardiography typically measures greater WT than CMR, with the largest differences in moderate to severe hypertrophy. Contrast echocardiography more closely approximates CMR measurements of WT. These findings have potential clinical implications for risk stratification of subjects with HCM. PMID- 26896039 TI - Admission Glucose Level Predicts In-hospital Mortality in Patients with Acute Pulmonary Embolism Who Were Treated with Thrombolytic Therapy. AB - BACKGROUND: Elevated admission serum glucose level is associated with unfavourable clinical outcomes in various clinical conditions. The aim of this study was to investigate the relationship between admission glucose levels and in hospital and long-term adverse clinical outcomes in patients with pulmonary embolism (PE) treated with thrombolytic therapy. METHODS: A total of 183 consecutive confirmed acute PE patients (98 female and 85 male; mean age 61.9 +/- 15.7 years) who were treated with thrombolytic therapy enrolled in this study. The study population was categorised into four quartiles according to admission serum glucose levels (group I: glucose <=115 mg/dl; group II: glucose >115-141 mg/dl; group III: glucose >141-195 mg/dl; and group IV: glucose >=196 mg/dl). RESULTS: In-hospital mortality was significantly higher in group IV (28.8 %) compared to group III (15.2 %), group II (6.6 %), and group I (2.1 %) (p < 0.001). In multivariate analysis, admission glucose level (OR 1.013, 95 % CI 1.004-1.021, p = 0.004) and admission anaemia (OR 0.602, 95 % CI 0.380-0.955, p = 0.03) were independent predictors of in-hospital mortality. The mean follow-up period was 34 months. During long-term follow-up, all-cause mortality, recurrent PE, major and minor bleeding were similar among the four groups. CONCLUSION: Admission glucose level is a simple, inexpensive, easily available, and effective laboratory parameter for predicting in-hospital mortality in patients with PE. PMID- 26896041 TI - Determinants of macroscopic anal cancer and precancerous lesions in 1206 HIV infected screened patients. AB - AIM: Anal screening is recommended in HIV-positive patients, especially men who have sex with men (MSM), due to an increased incidence of anal cancer. The optimal screening methods are not generally agreed. METHOD: Screening for anal lesions by anorectal examination, including anoscopy, was offered to HIV-positive outpatients in a tertiary care university hospital regardless of gender or sexual orientation. RESULTS: Among the 1206 screened patients (701 MSM, 247 heterosexual men, 258 women), 311 (26%) had histologically proven lesions related to human papilloma virus (HPV) (34% MSM, 14% heterosexual men, 14% women); 123 (10%) had low-grade dysplasia and 70 (6%) high-grade dysplasia. Seven anal cancers were also diagnosed. Determinants of any lesion were age < 45 years [OR = 1.56 (95% CI, 1.16-2.11)], a CD4 count of < 200/mm3 [OR = 2.54 (1.71-3.78)], receptive anal intercourse [OR =3.03 (2.06-4.47)], sub-Saharan African origin [OR = 0.53 (0.33 0.85)], and history of HPV-related lesion [OR = 1.84 (1.35-2.51)]. These determinants were similar for all different grades of dysplasia. In patient subgroup analysis, receptive anal intercourse, the CD4 cell count and a history of HPV lesions were determinants of HPV-positivity in all patients, whereas age was only a determinant in men. CONCLUSION: Anoscopy is an alternative method for anal screening in an HIV-positive population. This screening has to be compared with other tools in populations at high risk of anal cancer. PMID- 26896043 TI - Heat waves and the mentally ill. PMID- 26896040 TI - Optimizing Prophylactic CPAP in Patients Without Obstructive Sleep Apnoea for High-Risk Abdominal Surgeries: A Meta-regression Analysis. AB - INTRODUCTION: Prophylactic continuous positive airway pressure (CPAP) can prevent pulmonary adverse events following upper abdominal surgeries. The present meta regression evaluates and quantifies the effect of degree/duration of (CPAP) on the incidence of postoperative pulmonary events. METHODS: Medical databases were searched for randomized controlled trials involving adult patients, comparing the outcome in those receiving prophylactic postoperative CPAP versus no CPAP, undergoing high-risk abdominal surgeries. Our meta-analysis evaluated the relationship between the postoperative pulmonary complications and the use of CPAP. Furthermore, meta-regression was used to quantify the effect of cumulative duration and degree of CPAP on the measured outcomes. RESULTS: Seventy-three potentially relevant studies were identified, of which 11 had appropriate data, allowing us to compare a total of 362 and 363 patients in CPAP and control groups, respectively. Qualitatively, Odds ratio for CPAP showed protective effect for pneumonia [0.39 (0.19-0.78)], atelectasis [0.51 (0.32-0.80)] and pulmonary complications [0.37 (0.24-0.56)] with zero heterogeneity. For prevention of pulmonary complications, odds ratio was better for continuous than intermittent CPAP. Meta-regression demonstrated a positive correlation between the degree of CPAP and the incidence of pneumonia with a regression coefficient of +0.61 (95 % CI 0.02-1.21, P = 0.048, tau (2) = 0.078, r (2) = 7.87 %). Overall, adverse effects were similar with or without the use of CPAP. CONCLUSIONS: Prophylactic postoperative use of continuous CPAP significantly reduces the incidence of postoperative pneumonia, atelectasis and pulmonary complications in patients undergoing high-risk abdominal surgeries. Quantitatively, increasing the CPAP levels does not necessarily enhance the protective effect against pneumonia. Instead, protective effect diminishes with increasing degree of CPAP. PMID- 26896042 TI - Bayesian Models of Development. AB - Until recently, biology lacked a framework for studying how information from genes, parental effects, and different personal experiences is combined across the lifetime to affect phenotypic development. Over the past few years, researchers have begun to build such a framework, using models that incorporate Bayesian updating to study the evolution of developmental plasticity and developmental trajectories. Here, we describe the merits of a Bayesian approach to development, review the main findings and implications of the current set of models, and describe predictions that can be tested using protocols already used by empiricists. We suggest that a Bayesian perspective affords a simple and tractable way to conceptualize, explain, and predict how information combines across the lifetime to affect development. PMID- 26896044 TI - The treatment of suicidality in adolescents by psychosocial interventions for depression: A systematic literature review. AB - OBJECTIVE: Given depression is a significant risk factor for suicidal behaviour, it is possible that interventions for depression may also reduce the risk of suicide in adolescents. The purpose of this literature review is to determine whether psychological interventions aimed to prevent and/or treat depression in adolescents can also reduce suicidality. METHODS: We conducted a systematic review of psychological interventions aimed to prevent and/or treat depression in adolescents in which outcomes for suicidality were reported, using five databases: PsycINFO, Embase, Medline, CINAHL and Scopus. Study quality was assessed using the Cochrane Collaboration's tool for assessing risk of bias. RESULTS: A total of 35 articles pertaining to 12 treatment trials, two selective prevention trials and two universal prevention trials met inclusion criteria. No studies were identified that used a no-treatment control. In both intervention and active control groups, suicidality decreased over time; however, most structured psychological depression treatment interventions did not outperform pharmaceutical or treatment as usual control groups. Depression prevention studies demonstrated small but statistically significant reductions in suicidality. LIMITATIONS: Analysis of study quality suggested that at least 10 of the 16 studies have a high risk of bias. Conclusive comparisons across studies are problematic due to differences in measures, interventions, population differences and control groups used. CONCLUSIONS: It is unclear whether psychological treatments are more effective than no treatment since no study has used a no-treatment control group. There is evidence to suggest that Cognitive Behavioural Therapy interventions produce pre-post reductions in suicidality with moderate effect sizes and are at least as efficacious as pharmacotherapy in reducing suicidality; however, it is unclear whether these effects are sustained. There are several trials showing promising evidence for family-based and interpersonal therapies, with large pre-post effect sizes, and further evaluation with improved methodology is required. Depression prevention interventions show promising short-term effects. PMID- 26896045 TI - Experimental approaches in mechanotransduction: From molecules to pathology. PMID- 26896047 TI - Zika virus: What the neurologist wants to know. PMID- 26896046 TI - Cerebral hemodynamic changes during limb-shaking TIA: A near-infrared spectroscopy study. PMID- 26896048 TI - Huntington disease among the Navajo: A population-based study in the Navajo Nation. PMID- 26896049 TI - Impact of the Interval between Transarterial Chemoembolization Sessions on Survival in Patients with Unresectable Hepatocellular Carcinoma. AB - PURPOSE: To evaluate clinical impact of different intervals between multiple transarterial chemoembolization sessions in patients with unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A retrospective cohort study of 305 consecutive patients with HCC who underwent multiple sessions of on demand transarterial chemoembolization by two independent physicians with different management policies in terms of transarterial chemoembolization interval was performed; 180 patients had intervals between the first and second transarterial chemoembolization session of < 60 days (short-interval group), and 125 patients had transarterial chemoembolization intervals of >= 60 days (conventional-interval group). RESULTS: The short-interval group had more cases of advanced-stage HCC, less favorable response to transarterial chemoembolization, and higher likelihood of having Child-Pugh class A. The short interval group underwent more transarterial chemoembolization sessions (6.6 vs 5.5, P = .011), although the total number of admissions and total hospital stay were similar to the conventional-interval group. Overall survival was similar in the two groups in the full and the propensity score-matched cohorts. Although the overall survival of patients with Child-Pugh class A was comparable between the two groups in the full and propensity score-matched cohorts, the short-interval group showed inferior survival (P = .005) and a nonsignificant trend toward inferior survival (P = .117) in the full and propensity score-matched cohorts, respectively, for patients with Child-Pugh class B. CONCLUSIONS: Transarterial chemoembolization interval did not affect survival outcomes of patients with Child-Pugh class A. A shorter transarterial chemoembolization interval showed a nonsignificant trend of adversely affecting survival for patients with Child-Pugh class B. PMID- 26896050 TI - Inadvertent Intradiscal Injection with TFESI Utilizing Kambin's Retrodiscal Approach in the Treatment of Acute Lumbar Radiculopathy. AB - INTRODUCTION: There is very strong evidence for the efficacy of transforaminal epidural steroid injection (TFESI) in relieving lumbar radicular pain due to a herniated disk. However, case studies have documented paralysis as a potential complication from this approach as the artery of Adamkiewicz may traverse within the subpedicular "safe triangle." Kambin's retrodiscal approach has been postulated as a safe means to the transforaminal approach to avoid the artery of Adamkiewicz. CASE PRESENTATION: A 51-year-old woman presented with right-sided lumbar radicular pain at the L3-L4 and L4-L5 level secondary to a herniated disk. As conservative therapies failed to improve her radicular back pain, the patient opted to proceed with an epidural steroid injection. She subsequently underwent a right L3-L4 and L4-L5 transforaminal epidural steroid injection via Kambin's retrodiscal approach. Although anteroposterior and lateral views revealed optimal needle placement, live and postcontrast fluoroscopy revealed an unavoidable and inadvertent intradiscal spread. CONCLUSION: Kambin's approach is at the level of the intervertebral disk and may increase the incidence of intradiscal needle entry and injection. PMID- 26896051 TI - Should we add visual acuity ratios to referral criteria for potential cerebral visual impairment? AB - PURPOSE: To determine whether the assessment of visual acuity ratios might improve the referral of children with (sub)normal visual acuity but at risk of cerebral visual impairment. METHODS: In an exploratory study, we assessed visual acuity, crowding ratio and the ratios between grating acuity (Teller Acuity Cards II) and optotype acuity (Cambridge Crowding Cards) in 60 typically developing school children (mean age 5y8m+/-1y1m), 21 children with ocular abnormalities only (5y7m+/-1y9m) and 26 children with (suspected) brain damage (5y7m+/-1y11m). Sensitivities and specificities were calculated for targets and controls from the perspective of different groups of diagnosticians: youth health care professionals (target: children with any visual abnormalities), ophthalmologists and low vision experts (target: children at risk of cerebral visual impairment). RESULTS: For youth health care professionals subnormal visual acuity had the best sensitivity (76%) and specificity (70%). For ophthalmologists and low vision experts the crowding ratio had the best sensitivity (67%) and specificity (79 and 86%). CONCLUSION: Youth health care professionals best continue applying subnormal visual acuity for screening, whereas ophthalmologists and low vision experts best add the crowding ratio to their routine diagnostics, to distinguish children at risk of visual impairment in the context of brain damage from children with ocular pathology only. PMID- 26896052 TI - Genetic polymorphisms of 17 Y chromosomal STRs in She and Manchu ethnic populations from China. AB - To evaluate the utility of Yfiler haplotype for DNA testing in two ethnic populations of China, a sample of 413 unrelated individuals (152 Shes and 261 Manchus) was determined. In the She and Manchu populations, the haplotype diversity was 0.9990 and 0.9988, respectively, and the discrimination capacity was 0.9474 and 0.9080, respectively. Research results will be valuable for human identification and paternity tests in the two minority regions and for Chinese population genetic study in the future. PMID- 26896053 TI - Laparoscopic treatment of nonpalpable testicle. Factors predictive for diminished size. AB - PURPOSE: The purposes of this study were to demonstrate the usefulness of laparoscopy in intraabdominal testicle (IAT) and to determine factors associated with diminished size during the final outcome after laparoscopic orchidopexy. METHODS: This is a retrospective analysis of consecutive patients from 1999 to 2013 with a minimum follow-up of 1year. Patient and testicular factors were related to diminished size. RESULTS: Sixty one patients, and 92 testicles were included. Median age at operation was 42months. Initially we found 66 normal sized testes (71.7%), 22 hypotrophic (23.9%) and four atrophic (4.3%). Eighty seven testes were brought down laparoscopically, 50 in one surgical stage and 37 in two stages. Mean follow-up was 40.2months and the final outcome was success: 73.5% and diminished size: 26.5%. Variables associated with diminished size were hypotrophy during initial evaluation, short spermatic vessels, section of spermatic vessels, two-stage surgery and tension to reach contralateral inguinal ring. Multivariate analysis showed that initial hypotrophy (odds ratio [OR] 4.96, confidence interval 95% [CI] 1.36-18.10) and tension to reach contralateral ring (OR 4.11, 95% CI 1.18-14.34) were associated with diminished size. CONCLUSIONS: Laparoscopy is useful in treating IAT. Initial size and tension to reach contralateral ring are factors associated with diminished size. PMID- 26896054 TI - Evolutionary conservation of candidate osmoregulation genes in plant phloem sap feeding insects. AB - The high osmotic pressure generated by sugars in plant phloem sap is reduced in phloem-feeding aphids by sugar transformations and facilitated water flux in the gut. The genes mediating these osmoregulatory functions have been identified and validated empirically in the pea aphid Acyrthosiphon pisum: sucrase 1 (SUC1), a sucrase in glycoside hydrolase family 13 (GH13), and aquaporin 1 (AQP1), a member of the Drosophila integral protein (DRIP) family of aquaporins. Here, we describe molecular analysis of GH13 and AQP genes in phloem-feeding representatives of the four phloem-feeding groups: aphids (Myzus persicae), coccids (Planococcus citri), psyllids (Diaphorina citri, Bactericera cockerelli) and whiteflies (Bemisia tabaci MEAM1 and MED). A single candidate GH13-SUC gene and DRIP-AQP gene were identified in the genome/transcriptome of most insects tested by the criteria of sequence motif and gene expression in the gut. Exceptionally, the psyllid Ba. cockerelli transcriptome included a gut-expressed Pyrocoelia rufa integral protein (PRIP)-AQP, but has no DRIP-AQP transcripts, suggesting that PRIP-AQP is recruited for osmoregulatory function in this insect. This study indicates that phylogenetically related SUC and AQP genes may generally mediate osmoregulatory functions in these diverse phloem-feeding insects, and provides candidate genes for empirical validation and development as targets for osmotic disruption of pest species. PMID- 26896055 TI - Balancing Two Cultures: American Indian/Alaska Native Medical Students' Perceptions of Academic Medicine Careers. AB - American Indians and Alaska Natives (AI/AN) remain underrepresented in the academic medicine workforce and little is known about cultivating AI/AN medical students' interest in academic medicine careers. Five structured focus groups were conducted including 20 medical students and 18 physicians. The discussion guide explored factors influencing AI/AN trainees' academic medicine career interest and recommended approaches to increase their pursuit of academia. Consensual qualitative research was employed to analyze transcripts. Our research revealed six facilitating factors, nine dissuading factors, and five recommendations towards cultivating AI/AN pursuit of academia. Facilitators included the opportunity to teach, serving as a role model/mentor, enhancing the AI/AN medical education pipeline, opportunities to influence institution, collegiality, and financial stability. Dissuading factors included limited information on academic career paths, politics, lack of credit for teaching and community service, isolation, self-doubt, lower salary, lack of positions in rural areas, lack of focus on clinical care for AI/AN communities, and research obligations. Recommendations included heighten career awareness, recognize the challenges in balancing AI/AN and academic cultures, collaborate with IHS on faculty recruitment strategies, identify concordant role models/mentors, and identify loan forgiveness programs. Similar to other diverse medical students', raising awareness of academic career opportunities especially regarding teaching and community scholarship, access to concordant role models/mentors, and supportive institutional climates can also foster AI/AN medical students' pursuit of academia. Unique strategies for AI/AN trainees include learning how to balance AI/AN and academic cultures, collaborating with IHS on faculty recruitment strategies, and increasing faculty opportunities in rural areas. PMID- 26896056 TI - Prolonged Exclusive Breastfeeding Through Peer Support: A Cohort Study From a Community Outreach Project in Swaziland. AB - Swaziland faces great public health challenges, including suboptimal breastfeeding practices and the world's highest prevalence of HIV. The objective of this study was to estimate neonatal and infant mortality rate and rate of exclusive breastfeeding for clients enrolled in a community-based peer support project in peri-urban areas of Swaziland. The intervention builds on the so called "Philani-model" with Mentor Mothers in the community under high level of supervision. Cohort data was collected from journals kept by the Mentor Mothers. Kaplan-Meier and Cox regression were used to analyse data. Neonatal and infant mortality were estimated to 15 respectively 57 per 1000 live births. High level of social vulnerability was associated with risk of neonatal mortality (HR 1.12, CI 95 % 1.01-1.24) while the mother's positive HIV status was associated with infant mortality (HR 2.05, CI 95 % 1.15-3.65). More visits by a Mentor Mother could not be shown to result in lower mortality. The chance to practice exclusive breastfeeding for 6 months was estimated to 50 %. The risk of discontinuing exclusive breastfeeding before 6 months was lower for mothers being unemployed (HR 0.55, CI 95 % 0.44-0.69) or socially vulnerable (HR 0.95, CI 95 % 0.92-0.99) and higher for mothers being HIV positive (HR 1.22, CI 95 % 1.01-1.48). Receiving at least four visits by a Mentor Mother during pregnancy decreased the risk of discontinuing exclusive breastfeeding prematurely (HR 0.82, CI 95 % 0.67-0.99). Peer support with Mentor Mothers thus had a positive impact on exclusive breastfeeding rates in this disadvantaged population. PMID- 26896058 TI - Stress Tolerance of the Endemic Antarctic Brown Alga Desmarestia anceps to UV Radiation and Temperature is Mediated by High Concentrations of Phlorotannins. AB - The endemic Antarctic brown macroalga Desmarestia anceps is strongly shade adapted, but shows also a high capacity to cope with different environmental stressors, e.g. UV radiation and temperature. Therefore, this species colonizes wide depth gradients, which are characterized by changing environmental conditions. In this study, we examine whether the different physiological abilities allowing D. anceps to grow across a wide depth range is determined by high levels of phlorotannins. Photosynthesis, measured by PAM-fluorometry, the contents of soluble phlorotannins, antioxidant capacities of field grown were analyzed in response to different conditions of radiation (PAR and PAR + UV) and temperature (2, 7 and 12 degrees C). The results show that maximal quantum of fluorescence (Fv /Fm ) decreased with increasing doses of UV radiation, but remained unaffected by temperature. High levels of soluble phlorotannins were detected and confirmed by microscopic observation revealing the abundance of large physodes. Exposure to UV radiation and elevated temperature showed that phlorotannins were not inducible by UV but increased at 12 degrees C. ROS scavenging capacity was positively correlated with the contents of phlorotannins. In general, highest contents of phlorotannins were correlated with the lowest inhibition of Fv /Fm in all experimental treatments, highlighting the UV protective role of these compounds in D. anceps. PMID- 26896057 TI - The Eurasian invasion: phylogenomic data reveal multiple Southeast Asian origins for Indian Dragon Lizards. AB - BACKGROUND: The Indian Tectonic Plate split from Gondwanaland approximately 120 MYA and set the Indian subcontinent on a ~ 100 million year collision course with Eurasia. Many phylogenetic studies have demonstrated the Indian subcontinent brought with it an array of endemic faunas that evolved in situ during its journey, suggesting this isolated subcontinent served as a source of biodiversity subsequent to its collision with Eurasia. However, recent molecular studies suggest that Eurasia may have served as the faunal source for some of India's biodiversity, colonizing the subcontinent through land bridges between India and Eurasia during the early to middle Eocene (~35-40 MYA). In this study we investigate whether the Draconinae subfamily of the lizard family Agamidae is of Eurasian or Indian origin, using a multi locus Sanger dataset and a novel dataset of 4536 ultraconserved nuclear element loci. RESULTS: Results from our phylogenetic and biogeographic analyses revealed support for two independent colonizations of India from Eurasian ancestors during the early to late Eocene prior to the subcontinent's hard collision with Eurasia. CONCLUSION: These results are consistent with other faunal groups and new geologic models that suggest ephemeral Eocene land bridges may have allowed for dispersal and exchange of floras and faunas between India and Eurasia during the Eocene. PMID- 26896059 TI - Relationship between vitamin D deficiency and visually evoked potentials in multiple sclerosis. AB - OBJECTIVE: To evaluate the possible relationship between serum 25-OH vitamin D levels and visually evoked potentials (VEP) in patients with multiple sclerosis (MS), residents in the south zone of Gran Canaria. MATERIAL AND METHODS: The study included 49 patients with MS, on whom 25-OH-vitamin D was determined, along with VEP, and a neurological examination to determine incapacity. Clinical variables, such as a history of optic neuritis were recorded. RESULTS: The mean value of 25-OH-vitamin D of the patients was 28.1+/-9.5ng/ml. The VEP latency was 119.1+/-23.2ms and the amplitude, 8.5+/-4.4 MUV. Patients with a higher 25-OH vitamin D had a greater number of outbreaks in the year prior to the study (P=.049), and those with vitamin D deficiency and previous optic neuritis showed no reduction in the amplitude of the VEP (P=.006). CONCLUSION: Patients with vitamin D deficiency have lower clinical activity of the MS and show no axonal involvement in VEP after having suffered optic neuritis. These relationships, although statistically significant, do not seem clinically plausible, thus new studies are needed to try and confirm this possible relationship. PMID- 26896060 TI - Comparison of the characteristics in hen and quail corneas as experimental models of refractive surgery. AB - AIM: To compare the histological, morphological and the biophysical measurements between hen and quail corneas, in order to determine which of them were better suited for use as an animal model for research into corneal refractive surgery. MATERIAL AND METHODS: A study was performed using the biophysical measurements of the cornea (curvature, thickness, refraction, and axial length) of 20 animals (10 hens and 10 quails). The corneas were then prepared for histological analysis under microscopy light. RESULTS: The analysis showed that both groups have the same number of corneal layers as the human cornea and with an evident Bowman's layer. The thickness of the hen cornea and axial length of the eye, 225.3+/ 18.4MUm and 12.8+/-0.25mm, respectively, were larger than that of the quail (P<.01 and P<.001, respectively). The radius of curvature for the hen central cornea, 3.65+/-0.08mm, was greater than that for the quail (P<.001), but the refractive power of each cornea was similar. The proportion of total corneal thickness of the hen stroma, 82.6%, was more similar to that of the human than was the quail stroma, 72.5%. Within the hen stroma, the density of keratocytes, 8.57+/-1.49 per 5,000MUm(2), was about half that in the quail stroma (P<.005). CONCLUSIONS: Because of the large size of the hen cornea, the stromal thickness and proportional similarity of the corneal layers with human cornea, the hen maybe better than the quail as an alternative species suitable for use in studies of corneal refractive surgery. PMID- 26896061 TI - Vladimir Petrovich Filatov, one of the fathers of corneal transplant. PMID- 26896062 TI - A curious fact: Photic sneeze reflex. Autosomical dominant compelling helio ophthalmic outburst syndrome. AB - OBJECTIVE: To assess ocular involvement in the pathophysiology of autosomal dominant compelling helio-ophthalmic outburst syndrome (ACHOOs). METHODS: An interview was conducted with a Caucasian family that showed clinical features of ACHOOs. Twelve of them had photic reflex and were recruited. A complete eye evaluation was made. RESULTS: A dominant autosomal inheritance with mild penetrance was demonstrated, with 67% of the studied subjects showing some degree of prominent corneal nerves. No other eye changes were found. CONCLUSIONS: Prominent corneal nerves may be associated with ACHOOs. The other eye structures studied do not seem to play a role in ACHOOs. Further studies are needed to understand the physiology of the ACHOOs. PMID- 26896063 TI - Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: A case report. AB - CLINICAL CASE: A five-year-old patient, with a diagnosis of long-chain 3 hydroxyacyl-CoA dehydrogenase deficiency, was referred for an ophthalmological examination. He had a history of acute metabolic crises precipitated by intercurrent infections,as well as rhabdomyolysis. The fundoscopic examination revealed a peripapillary chorioretinal atrophy and a diffuse granular appearance of the macular retinal pigment epithelium. Best corrected visual acuity was 6/6 in both eyes, and he had a normal electroretinography test. DISCUSSION: We perform a review of the literature and recent findings in relation to this disease through the description of a clinical case in order to improve the knowledge of this uncommon disorder. PMID- 26896064 TI - Louis Braille: Light for blind. PMID- 26896065 TI - Branch retinal artery occlusion in a patient with one eye. Laser Nd:YAG approach. AB - CLINICAL CASE: An 82-year-old man was admitted to the emergency department complaining of a sudden painless visual loss in his left eye (OS). He was diagnosed with branch retinal artery occlusion (BRAO) with a visible embolus. In 2012, he had a central artery occlusion (CRAO) in his right eye (OD). An embolysis with Nd:YAG laser was attempted, the retinal arterial blood flow was restored completely and the visual field was improved, with no secondary complications. CONCLUSIONS: Nd:YAG laser embolysis is a treatment to be considered in patients with BRAO with a visible embolus. The risks and benefits of the procedure should be evaluated, comparing it with possible permanent loss of visual acuity and other vascular complications caused by BRAO. PMID- 26896066 TI - Increased level of reactive oxygen species persuades postovulatory aging-mediated spontaneous egg activation in rat eggs cultured in vitro. AB - The present study was aimed to find out whether increased level of reactive oxygen species (ROS) particularity hydrogen peroxide (H2O2) could persuade postovulatory aging-mediated abortive spontaneous egg activation (SEA) in rat eggs cultured in vitro. For this purpose, ROS and H2O2 levels, mitochondria distribution and its membrane potential, p286-CaMK-II, Emi2, Thr-161 phophorylated cyclin-dependent protein kinase1 (Cdk1) as well as cyclin B1 levels, in vitro effects of 3-tert-butyl-4 hydroxy anisole (BHA), pentoxifylline and dibutyryl-adenosine 3',5'-cyclic monophosphate (db-cAMP) were analyzed during postovulatory aging-induced abortive SEA in vitro. Data of the present study suggest that postovulatory aging increased H2O2 levels, disturbed mitochondrial distribution pattern and mitochondrial membrane potential (MMP) in eggs. There was an significant increase of p286-CaMK-II level, while Emi2 level reduced significantly during egg aging in vitro. The reduced Emi2 level was associated with decreased Thr-161 phosphorylated cyclin-dependent kinase-1 (Cdk1) as well as cyclin B1 level in aged eggs that underwent abortive SEA. Further, supplementation of pentoxifylline, db-cAMP, and BHA protected postovulatory aging mediated abortive SEA in concentration-dependent manner. These data suggest that postovulatory aging increased H2O2 levels, reduced MMP, and increased p286-CaMK II. The increased p286-CaMK-II was associated with reduced Emi2 level and maturation-promoting factor levels during postovulatory aging-mediated abortive SEA. Drugs that elevate cAMP directly or indirectly and BHA protected postovulatory aging-mediated abortive SEA possibly by reducing ROS level in rat eggs cultured in vitro. PMID- 26896067 TI - The Effect of Nitric Oxide on Ammonia Decomposition in Co-cultures of Hepatocytes and Hepatic Stellate Cells. AB - Hepatic functions, such as albumin secretion and ammonia metabolism, are upregulated in response to hepatocyte growth factor (HGF) produced by hepatic stellate cells (HSC), as well as nitric oxide (NO) produced by endothelial cells under shear stress. However, the simultaneous effect of HSC and NO has not been previously investigated in a tri-co-culture model containing hepatocytes with HSC and endothelial cells under shear stress. We hypothesized that NO inhibits HGF production from HSC. To test this idea, we constructed a mono-culture model of hepatocytes and a co-culture model of hepatocytes and HSC and measured ammonia decomposition and HGF production in each model under NO load. Ammonia decomposition was significantly higher in the co-culture model under 0 ppm NO load, but no significant increase was observed under NO load. In the co-culture model, HGF was produced at 1.0 ng/mL under 0 ppm NO load and 0.3 ng/mL under NO load. Ammonia decomposition was increased by 1.0 ng/mL HGF, but not by 0.3 ng/mL HGF. These results indicated that NO inhibits HGF production from HSC; consequently, the effects of NO and co-culture with HSC cannot improve hepatic function simultaneously. Instead, the simultaneous effect of 1.0 ng/mL HGF and NO may further enhance hepatic function in vitro. PMID- 26896069 TI - Importance of a Proper Design for Sham Acupuncture Treatment. PMID- 26896068 TI - Combination of metformin and 5-aminosalicylic acid cooperates to decrease proliferation and induce apoptosis in colorectal cancer cell lines. AB - BACKGROUND: The link between inflammation and cancer has been confirmed by the use of anti-inflammatory therapies in cancer prevention and treatment. 5 aminosalicylic acid (5-ASA) was shown to decrease the growth and survival of colorectal cancer (CRC) cells. Studies also revealed that metformin induced apoptosis in several cancer cell lines. METHODS: We investigated the combinatory effect of 5-ASA and metformin on HCT-116 and Caco-2 CRC cell lines. Apoptotic markers were determined using western blotting. Expression of pro-inflammatory cytokines was determined by RT-PCR. Inflammatory transcription factors and metastatic markers were measured by ELISA. RESULTS: Metformin enhanced CRC cell death induced by 5-ASA through significant increase in oxidative stress and activation of apoptotic machinery. Moreover, metformin enhanced the anti inflammatory effect of 5-ASA by decreasing the gene expression of IL-1beta, IL-6, COX-2 and TNF-alpha and its receptors; TNF-R1 and TNF-R2. Significant inhibition of activation of NF-kappaB and STAT3 transcription factors, and their downstream targets was also observed. Metformin also enhanced the inhibitory effect of 5-ASA on MMP-2 and MMP-9 enzyme activity, indicating a decrease in metastasis. CONCLUSION: The current data demonstrate that metformin potentiates the antitumor effect of 5-ASA on CRC cells suggesting their potential use as an adjuvant treatment in CRC. PMID- 26896071 TI - Acupressure on Self-Reported Sleep Quality During Pregnancy. AB - The aim of this study was to investigate the short-term effect of acupression at the H7 point on sleep quality during pregnancy. After oral consent had been obtained, the midwife invited the women claiming to have poor sleep quality and anxiety symptoms to complete the Pittsburgh Sleep Quality Index questionnaire and the State-Trait Anxiety Inventory-1. Then, the same midwife, previously trained by an expert acupuncturist (I.N.), advised the women to put on the wrist overnight compression H7 Insomnia Control half an hour before going to bed and to take it off upon awakening, for 10 consecutive days and thereafter every odd day (active group). Women refusing to wear the device for low compliance toward acupression were considered as the control group. After 2 weeks, a second questionnaire evaluation was completed. In the active, but not in the control, group, a significant improvement of sleep quality was observed after H7 device application. The study suggests that H7 acupression applied for 2 weeks improves sleep quality in pregnant women. This preliminary result should serve to stimulate further studies on the long-term effects of acupression. PMID- 26896070 TI - Hypothalamic Norepinephrine Mediates Acupunctural Effects on Hypothalamic Pituitary-Adrenal Axis During Ethanol Withdrawal. AB - A previous study demonstrated that acupuncture at ST36 (Zu-San-Li) attenuates ethanol withdrawal (EW)-induced hyperactivation of the hypothalamic-pituitary adrenal axis in rats. The current study investigated the involvement of hypothalamic norepinephrine (NE) in that process. Rats were intraperitoneally treated with 3 g/kg/d of ethanol or saline for 28 days. After 24 hours of EW, acupuncture was applied to rats at bilateral ST36 points or at nonacupoints (tail) for 1 minute. A high-performance liquid chromatography analysis showed that EW significantly increased both the NE and the 3-methoxy-4-hydroxy phenylglycol (MHPG) levels in the hypothalamic paraventricular nucleus (PVN). Western blot analysis also revealed that EW markedly elevated the phosphorylation rates of tyrosine hydroxylase (TH), but spared TH protein expression in the PVN. However, acupuncture at ST36, but not at nonacupoints, greatly inhibited the increase in the hypothalamic NE, MHPG, and phosphorylation rates of TH. Additionally, postacupuncture infusion of NE into the PVN significantly attenuated the inhibitory effects of acupuncture at ST36 on the oversecretion of plasma corticosterone during EW. These results suggest that acupuncture at ST36 inhibits EW-induced hyperactivation of the hypothalamic NEergic system to produce therapeutic effects on the hypothalamic-pituitary-adrenal axis. PMID- 26896072 TI - Preemptive Analgesia with Acupuncture Monitored by c-Fos Expression in Rats. AB - Pain behavior and awareness are characterized by heightened alertness and anxiety, which begin to disappear as soon as the curative process starts. The present study aimed to quantify c-fos expression in rat spinal cords and brains after a surgical stimulus and with preoperative or postoperative acupuncture. Animals were randomly divided into preoperative and postoperative groups and were then further divided into control, manual acupuncture (MA), or electroacupuncture (EA) groups. Expression of c-fos was quantified using immunohistochemistry. The collected data were analyzed using the t test at a 5% probability level. Presurgery and postsurgery spinal cord c-fos expressions were similar in all of the treatment groups. In the control rats, c-fos expression was higher before surgery than after surgery, contradicting the expected outcome of acupuncture and preemptive analgesia. After treatment, the expression of c-fos in the brains of the rats in the MA and the EA groups was reduced compared with that of the rats in the control group. These findings suggest that acupuncture used as preemptive analgesia in rats is a useful model for studying its application in human treatment. PMID- 26896073 TI - Waiguan Stimulation May Kindle Anticorrelated Brain Networks: Functional Magnetic Resonance Imaging Data Revisited. AB - Subtraction of functional magnetic resonance imaging activity data results in a loss of information regarding possible general patterns of brain activation under experimental conditions. We, hence, reanalyzed previous Waiguan acupuncture data to qualitatively elucidate patterns of cerebral correlations to acupuncture and placebo conditions. Healthy individuals (n=24) were randomly allocated to true and sham Waiguan acupuncture and to true and sham needling of a nonacupuncture point (nonacupoint), and functional magnetic resonance imaging scans were performed during stimulation. Statistical parametric mapping group comparisons revealed clearly different patterns of activation between Waiguan stimulation and the corresponding stimulation of a nonacupoint. The former condition produced less neocortical activation than the nonacupoint stimulation. Cerebellar activation was typically seen only during true Waiguan acupuncture. The reduced neocortical activity during both true and sham Waiguan acupuncture may indicate that this point activates anticorrelated networks, with possible intrinsic healing properties. Cerebellar activation during true Waiguan acupuncture implies the region's influence on healing networks. PMID- 26896074 TI - Effects of Acupuncture at the Yintang and the Chengjiang Acupoints on Cardiac Arrhythmias and Neurocardiogenic Syncope in Emergency First Aid. AB - This study evaluated the effectiveness of YinTang and ChengJiang acupoints on patients with cardiac arrhythmia and neurocardiogenic syncope in emergency first aid. A 45 year old woman underwent acupuncture. She had a previous history of a valvuloplasty for rheumatic disease and two acute myocardial infarctions, followed by four catheterizations and an angioplasty. Needling of the YinTang acupoint and stimulation of the ChengJiang acupoint through acupressure were performed for 20 minutes soon after syncope and during tachycardia, hypertension, tachypnea, and precordial pain, without any effect on peripheral oxygen saturation (SpO2) or the glycemic index. Data were analyzed comparatively by using the following parameters at rest, during syncope, and at 1 minute and 10 minutes after an emergency acupuncture procedure: blood pressure; heart rate; SpO2; and respiratory rate. We found that acupuncture at YinTang and ChenJiang acupoints induced cardiovascular responses, increased the limits of the body's homeostasis, and normalized the patient's condition in the case of syncope. Acupuncture using a combination of ChengJiang and YinTang acupoints had an immediate effect on the autonomic nervous system and on maintaining homeostasis and energy balance in the body. Although this technique was effective, the patient was still referred to the Emergency Room. PMID- 26896076 TI - Erratum to: Bacteria-induced hatching of Trichuris muris eggs occurs without direct contact between eggs and bacteria. PMID- 26896075 TI - Clinical Effect of Acupotomy Combined with Korean Medicine: A Case Series of a Herniated Intervertebral Disc. AB - The aim of this study is to evaluate the effect of acupotomy for treating patients with a herniated intervertebral disc (HIVD). This case series includes five HIVD patients who were treated at the Department of Acupuncture and Moxibustion, Daejeon University Dunsan Korean Hospital, Daejeon, Korea, from January 2015 to April 2015. Acupotomy was performed three times over a 2-week period, along with Korean medical treatment. The outcomes were evaluated by using a numeric rating scale (NRS), physical examination, the Oswestry Low Back Pain Disability Index (ODI), the Short-Form 36-Item Health Survey (SF-36), and the Surgical Safety Checklist. The NRS and physical examination results, as well as the ODI scores, were improved in all cases. No significant differences were noted on the SF-36. No patients had any adverse effects. This study, with its findings of encouraging responses in reducing low back pain and radiating pain and in recovering the kinetic state of soft tissue, supports the potential use of acupotomy for the treatment of patients suffering from HIVD. PMID- 26896078 TI - Letter to the editor in response to: Tay BD, Prabhu IS, Cousin CH, et al. Occupational exposure to noise in maxillofacial operating theatres: an initial prospective study. Br J Oral Maxillofac Surg. 2016;54:94-6. PMID- 26896077 TI - Identification of piroplasm infection in questing ticks by RLB: a broad range extension of tick-borne piroplasm in China? AB - Sensitive and specific diagnostic method for rapid and simultaneous detection and discrimination of the different species is needed for an effective control of piroplasmosis. Here, a reverse line blot (RLB) assay was developed for piroplasm detection. A general pair of primer based on 18S ribosomal RNA (rRNA) gene was used to amplify V4 region of 18S rRNA gene. General and specific probes for 13 piroplasm species were cited from previous publications or designed according to the alignment of 18S rRNA gene sequences. For sensitivity test of RLB assay, serially diluted plasmids of the different species were used to access the sensitivity of the RLB. Four hundred and fifty tick samples collected from grass from different provinces of China were then detected. The result indicated that the RLB assay is highly specific and sensitive, detecting up to 10(2) copies/MUl of recombinant plasmid DNA. Multiple piroplasms were detected as single or mixed infection from tick species. Eight piroplasm species, most of which were Theileria annulata (33/450, 7.3 %) or Babesia sp. Xinjiang (30/450, 6.7 %), were found to infect with 89 tick samples in four tick species; no infections with Babesia major, Babesia ovata, Babesia bigemina, Theileria sergenti, or Theileria equi were detected. The piroplasms species-specific RLB assay may have potential clinical application in the simultaneous detection and differentiation of Babesia and Theileria species. PMID- 26896079 TI - Natural position of the head: review of two-dimensional and three-dimensional methods of recording. AB - Both the correct position of the patient's head and a standard system for the acquisition of images are essential for objective evaluation of the facial profile and the skull, and for longitudinal superimposition. The natural position of the head was introduced into orthodontics in the late 1950s, and is used as a postural basis for craniocervical and craniofacial morphological analysis. It can also have a role in the planning of the surgical correction of craniomaxillofacial deformities. The relatively recent transition in orthodontics from 2-dimensional to 3-dimensional imaging, and from analogue to digital technology, has renewed attention in finding a versatile method for the establishment of an accurate and reliable head position during the acquisition of serial records. In this review we discuss definition, clinical applications, and procedures to establish the natural head position and their reproducibility. We also consider methods to reproduce and record the position in two and three planes. PMID- 26896080 TI - Infraorbital necrotising fasciitis: importance of rehabilitation in vulnerable patients. PMID- 26896081 TI - Re: Tumour progression or pseudoprogression? A review of post-treatment radiological appearances of glioblastoma. PMID- 26896082 TI - Undergraduate radiology teaching in a UK medical school: a systematic evaluation of current practice. AB - AIM: To use the Royal College of Radiologists' Undergraduate Radiology Curriculum (RCR URC) as an innovative tool to review undergraduate radiology teaching and ensure it is comprehensive and balanced. MATERIALS AND METHODS: Quantitative and qualitative methods were used to audit and review radiology teaching for students in years 1-3. All radiological teaching on the course was mapped against the RCR URC learning outcomes. An online survey of students in year 3 (n=138) was conducted using Likert (1-5), multiple choice, and free-text questions. RESULTS: There were 954 instances of radiology teaching, with 70% occurring during lectures. Radiology teaching was mapped to 81 of the 96 RCR URC learning outcomes (84.4%). Forty-seven of 138 students responded to the survey. They expressed confidence in understanding what basic imaging entails (x=4.23) and the risks associated with various imaging techniques (x=4.34). They were also confident in chest radiograph interpretation (x=3.62), but were less confident understanding abdominal radiographs (x=2.87). In free-text comments, students requested more tutorial-type teaching and ultrasound instruction. CONCLUSION: The RCR URC is an effective tool for auditing undergraduate radiology teaching, and other medical schools may, therefore, benefit from using this method. This evaluation process incorporating audit and feedback has identified areas for curriculum development. These include incorporating ultrasound into teaching sessions, delivering more small-group teaching, and introducing clinical placements in radiology departments. PMID- 26896083 TI - Sclerostin expression in bone tumours and tumour-like lesions. AB - AIMS: To assess the immunophenotypic and mRNA expression of sclerostin in human skeletal tissues and in a wide range of benign and malignant bone tumours and tumour-like lesions. METHODS AND RESULTS: Sclerostin expression was evaluated by immunohistochemistry and quantitative polymerase chain reaction (PCR). In lamellar and woven bone, there was strong sclerostin expression by osteocytes. Osteoblasts and other cell types in bone were negative. Hypertrophic chondrocytes in the growth plate and mineralized cartilage cells in zone 4 of hyaline articular cartilage strongly expressed sclerostin, but most chondrocytes in hyaline cartilage were negative. In primary bone-forming tumours, including osteosarcomas, there was patchy expression of sclerostin in mineralized osteoid and bone. Sclerostin staining was seen in woven bone in fibrous dysplasia, in osteofibrous dysplasia, and in reactive bone formed in fracture callus, in myositis ossificans, and in the wall of solitary bone cysts and aneurysmal bone cysts. Sclerostin was expressed by hypertrophic chondrocytes in osteochondroma and chondroblasts in chondroblastoma, but not by tumour cells in other bone tumours, including myeloma and metastatic carcinoma. mRNA expression of sclerostin was identified by quantitative PCR in osteosarcoma specimens and cell lines. CONCLUSIONS: Sclerostin is an osteocyte marker that is strongly expressed in human woven and lamellar bone and mineralizing chondrocytes. This makes it a useful marker with which to identify benign and malignant osteogenic tumours and mineralizing cartilage tumours, such as chondroblastomas and other lesions in which there is bone formation. PMID- 26896084 TI - Intraluminal Injection of Mesenchymal Stromal Cells in Spheroids Attenuates Experimental Colitis. AB - BACKGROUND AND AIMS: In recent years, mesenchymal stromal cells [MSCs] emerged as a promising therapeutic option for various diseases, due to their immunomodulatory properties. We previously observed that intraperitoneally injected MSCs in experimental colitis form spherical shaped aggregates. Therefore, we aggregated MSCs in vitro into spheroids and injected them intraluminally in mice with established colitis, to investigate whether these MSC spheroids could alleviate the colitis. METHODS: We injected 0.5 x 10(6) MSCs in spheroids, 2.0 x 10(6) MSCs in spheroids, or phosphate-buffered saline [PBS] as a treatment control, via an enema in mice with established dextran sulphate sodium [DSS]-induced colitis. Body weight was measured daily and disease activity score was determined at sacrifice. Endoscopy was performed to evaluate mucosal healing. After sacrifice, both systemic and local inflammatory responses were evaluated. RESULTS: Intraluminally injected MSC spheroids alleviated DSS-induced colitis, resulting in significantly less body weight loss and lower disease activity score at sacrifice when a high dose of MSC spheroids was administered. However, the percentage of mucosal lesions in the distal colon and endoscopy scores were not significantly lower after treatment with 2.0 x 10(6) MSCs in spheroids compared with PBS-treated mice. Systemic inflammation marker serum amyloid A [SAA] was significantly reduced after treatment with 2.0 x 10(6) MSCs in spheroids. In addition, local cytokine levels of IFN-gamma, TNF-alpha, IL-6, and IL-17a, as well as numbers of macrophages and neutrophils, showed a clear decrease-though not always significant-after intraluminal injection of the MSC spheroids. CONCLUSION: Intraluminally injected MSC spheroids at least partially attenuate experimental colitis, with fewer phagocytes and proinflammmatory cytokines, when a high dose of MSCs in spheroids was administered. PMID- 26896085 TI - Anti-TNF Therapy Response in Patients with Ulcerative Colitis Is Associated with Colonic Antimicrobial Peptide Expression and Microbiota Composition. AB - BACKGROUND AND AIMS: Anti-tumour necrosis factor [TNF] therapy is used in patients with ulcerative colitis [UC], but not all patients respond to treatment. Antimicrobial peptides [AMPs] and the gut microbiota are essential for gut homeostasis and may be important for treatment outcome. The aim of this study was to determine AMP and microbiota profiles in patients with UC before anti-TNF therapy start and correlate these data to treatment outcome. METHODS: Serum and biopsies were obtained from UC patients naive to biological therapy [n = 56] before anti-TNF therapy start [baseline]. Fecal samples were taken at baseline and Weeks 2 and 6. Quantitative proteomic analysis was performed in mucosal biopsies. Expression of AMPs and cytokines was determined in biopsies and serum. Microbiota analysis of fecal samples was performed using GA-mapTM Dysbiosis Test and real-time quantitative polymerase chain reaction [rtPCR]. Treatment response was evaluated 12-14 weeks after baseline. RESULTS: At baseline, proteomic analysis of biopsies showed that treatment responders and non-responders had differential expression of AMPs. Eleven AMP and AMP-related genes were analysed by rtPCR in mucosal biopsies and could together discriminate responders from non responders at baseline. The most important nominators for response were increased expression of defensin 5 and eosinophilic cationic protein. Microbiota analysis revealed lower dysbiosis indexes and higher abundance of Faecalibacterium prausnitzii in responders compared with non-responders at baseline. Also, abundance of F. prausnitzii increased during induction therapy in responders. CONCLUSIONS: Anti-TNF therapy responders and non-responders display distinctly separate patterns of mucosal AMP expression and gut microbiota before treatment start. This indicates that intestinal antimicrobial/microbial composition can influence treatment outcome. PMID- 26896086 TI - Mechanism of Action of Anti-TNF Therapy in Inflammatory Bowel Disease. AB - Several anti-tumour necrosis factor [TNF] blocking strategies have been evaluated in patients with Crohn's disease. Compounds that have been tested included the full monoclonal IgG1 antibodies infliximab and adalimumab, the pegylated anti-TNF F[ab']2 fragment certolizumab, an IgG4 anti-TNF CDP571 with reduced affinity for the Fc receptor, the soluble TNF receptor I onercept, and the TNF receptor II-Fc fusion protein etanercept. The endpoints of these studies suggest that not all methods of blocking TNF are equal. Here we will review the differences in the clinical, biochemical, and endoscopic endpoints of the major clinical studies. Collectively the data suggest that only IgG1 monoclonal antibodies have the ability to induce complete clinical, biochemical, and endoscopic remission. We discuss the potential multiple modes of action that may contribute to the response to full IgG1 anti-TNFs, focusing on the rapid induction of lamina propria T cell apoptosis and Fc receptor-dependent induction of M2-type wound healing macrophages. We discuss how novel insights into the mechanism of action of anti-TNFs in Crohn's disease may contribute to the development of novel anti TNFs with improved efficacy. PMID- 26896087 TI - Perceptions and Attitudes Towards Medication Adherence during Pregnancy in Inflammatory Bowel Disease. AB - BACKGROUND AND AIMS: Women with inflammatory bowel disease [IBD] report concerns about medication safety during pregnancy. Adherence to IBD medications may be lower in pregnant patients as a result. The aim of this study was to assess medication adherence during pregnancy in women with inflammatory bowel disease. METHODS: Female patients of childbearing age completed a self-administered, structured survey. We collected demographic data, medication history, and self reported adherence to IBD medications during pregnancy. We also assessed knowledge and perceptions of IBD medication safety in pregnancy. A time trade-off [TTO] analysis was done to assess health utilities for continuing or discontinuing IBD medications during pregnancy. RESULTS: A total of 204 women completed the survey [mean age was 32.8 years]. Current or previous pregnancy was reported by 101 patients [median parity 2, median gravity 1]. While pregnant or attempting to conceive, 47 [46.5%] participants reported stopping a prescribed IBD medication. Of those, 20 participants reported stopping medications without the advice of a physician. TTO analysis was completed by 31 patients. When presented with the option of continuing a potentially teratogenic medication, switching to less effective medication that is non-teratogenic, or stopping medication all together, participants consistently preferred to not remain on the most effective IBD therapy. CONCLUSIONS: Women with IBD report preference to not remain on IBD medications during pregnancy. This is driven by concerns about safety and uncertainty about teratogenic effects. Women with IBD may benefit from increased education about medication safety in pregnancy. PMID- 26896088 TI - Integrated decoys and effector traps: how to catch a plant pathogen. AB - Plant immune receptors involved in disease resistance and crop protection are related to the animal Nod-like receptor (NLR) class, and recognise the virulence effectors of plant pathogens, whereby they arm the plant's defensive response. Although plant NLRs mainly contain three protein domains, about 10% of these receptors identified by extensive cross-plant species data base searches have now been shown to include novel and highly variable integrated domains, some of which have been shown to detect pathogen effectors by direct interaction. Sarris et al. have identified a large number of integrated domains that can be used to detect effector targets in host plant proteomes and identify unknown pathogen effectors.Please see related Research article: Comparative analysis of plant immune receptor architectures uncovers host proteins likely targeted by pathogens, http://dx.doi.org/10.1186/s12915-016-0228-7 Since the time of writing, a closely related paper has been released: Kroj T, Chanclud E, Michel-Romiti C, Grand X, Morel J-B. Integration of decoy domains derived from protein targets of pathogen effectors into plant immune receptors is widespread. New Phytol. 2016 (ahead of print). PMID- 26896089 TI - Outbreak of plasmid-mediated NDM-1-producing Klebsiella pneumoniae ST105 among neonatal patients in Yunnan, China. AB - BACKGROUND: In the past decade, the carbapenemase-producing Enterobacteriaceae (CPE) have been reported worldwide. Emergence of carbapenemase-producing strains among Enterobacteriaceae has been a challenge for treatment of clinical infection. The present study was undertaken to investigate the characteristics of carbapenem-resistant Klebsiella pneumoniae recovered from an outbreak that affected 17 neonatal patients in neonatal intensive care unit (NICU) of Kunming City Maternal and Child health Hospital, which is located in the Kunming city in far southwest of China. METHODS: Minimum inhibitory concentrations (MICs) for antimicrobial agents were determined according to the guidelines of the Clinical and Laboratory Standards Institute (CLSI); Modified Hodge test and Carba-NP test were preformed to identified the phenotypes of carbapenemases producing; To determine whether carbapenem resistance was transferable, a conjugation experiment was carried out in mixed broth cultures; Resistant genes were detected by using PCR and sequencing; Plasmids were typed by PCR-based replicon typing method; Clone relationships were analyzed by using multilocus-sequence typing (MLST) and pulsed field gel electrophoresis (PFGE). RESULTS: Eighteen highly carbapenem-resistant Klebsiella pneumoniae were isolated from patients in NICU and one carbapenem-resistant K. pneumoniae isolate was detected in incubator water. All these isolates harbored bla NDM-1. Moreover, other resistance genes, viz., bla IMP-4 , bla SHV-1 , bla TEM-1 , bla CTX-M-15 , qnrS1, qnrB4, and aacA4 were detected. The bla NDM-1 gene was located on a ca. 50 kb IncFI type plasmid. PFGE analysis showed that NDM-1-producing K. pneumoniae were clonally related and MLST assigned them to sequence type 105. CONCLUSIONS: NDM-1 producing strains present in the hospital environment pose a potential risk and the incubator water may act as a diffusion reservoir of NDM-1- producing bacteria. Nosocomial surveillance system should play a more important role in the infection control to limit the spread of these pathogens. PMID- 26896090 TI - A longitudinal study of a family with adult-onset autosomal dominant leukodystrophy: Clinical, autonomic and neuropsychological findings. AB - BACKGROUND AND PURPOSE: Adult-onset autosomal dominant leukodystrophy (ADLD) is a rare progressive neurological disorder caused by Lamin B1 duplication (LMNB1). Our aim was to investigate longitudinally the pattern of the autonomic dysfunction and the degree of neuropsychological involvement. METHODS: Three related ADLD patients and one asymptomatic carrier of LMNB1 duplication underwent a standardized evaluation of autonomic nervous system, including cardiovascular reflexes, pharmacological testing, microneurography, skin biopsy, Metaiodobenzylguanidine scintigraphy and a complete neuropsychological battery. RESULTS: An early neurogenic orthostatic hypotension was detected in all patients and confirmed by a low rise in noradrenaline levels on Tilt Test. However infusion of noradrenaline resulted in normal blood pressure rise as well as the infusion of clonidine. At the insulin tolerance test the increase in adrenaline resulted pathological in two out three patients. Microneurography failed to detect muscle sympathetic nerve activity bursts. Skin biopsy revealed a poor adrenergic innervation, while cardiac sympathetic nerves were normal. None of ADLD patients showed a global cognitive deficit but a selective impairment in the executive functions. CONCLUSION: Autonomic disorder in ADLD involves selectively the postganglionic sympathetic system including the sympatho-adrenal response. Cognitive involvement consisting in an early impairment of executive tasks that might precede brain MR abnormalities. PMID- 26896091 TI - Delayed Fever and Neurological Outcome after Cardiac Arrest: A Retrospective Clinical Study. AB - BACKGROUND: The aim of this study was to evaluate the association between fever after the first days of ICU stay and neurological outcome after cardiac arrest (CA). METHODS: We retrospectively analyzed CA patients admitted to intensive care unit (ICU). INCLUSION CRITERIA: age >=18 years, Glasgow Coma Scale score <=8 at ICU admission and assessment of body core temperature (BCT) using bladder or intravascular probes. EXCLUSION CRITERIA: ICU length of stay (LOS) <3 days and pregnancy. The primary endpoint was neurological outcome assessed with Cerebral Performance Category (CPC) scale 6 months after CA. RESULTS: One hundred thirty two patients were analyzed. Fever was present in 105 (79.6%) patients. Variables associated with unfavorable outcome were (1) older age (p < 0.0025); (2) non shockable cardiac rhythms (p < 0.0001); (3) higher Simplified Acute Physiology Score (SAPS) II (p < 0.0001); (4) pupillary abnormalities at ICU admission (p < 0.018); and (5) elevated degree of maximal BCT (Tmax) during ICU stay (p < 0.046). After multivariate analysis, Tmax maintained a significant relationship with neurological outcome. An increase of 1 degrees C in Tmax during ICU stay decreased the odds ratio for a favorable outcome by a factor of 31% (p < 0.001). Moreover, we discovered a significant interaction between the day of Tmax (t Tmax) and Tmax (p = 0.004); the later Tmax occurs, the more deleterious effects are observed on outcome. CONCLUSIONS: Fever is frequent after CA, and Tmax in ICU is associated with worsened neurological outcome. This association becomes stronger as the timing of Tmax extends further from the CA. PMID- 26896092 TI - Risk of Venous Thromboembolism in Patients with Large Hemispheric Infarction Undergoing Decompressive Hemicraniectomy. AB - BACKGROUND: Deep-venous thrombosis (DVT) and pulmonary embolism (PE) are major causes of morbidity and mortality in patients with acute ischemic stroke. This study is the first to examine the risk of venous thromboembolism in patients with large hemispheric infarction undergoing decompressive hemicraniectomy. METHODS: The study population included 95 consecutive patients with a large hemispheric infarction who underwent decompressive hemicraniectomy between 2006 and 2014 at our institution. All patients received prophylactic unfractionated heparin and intermittent compression devices (SCD). Patients were systematically screened for DVT at 5-day interval using Duplex ultrasound. PE was diagnosed on chest CT angiography. RESULTS: Mean age was 57 +/- 12 years; mean BMI was 28.3 +/- 7.4 kg/m(2). 30.5 % of patients had infarction in the dominant hemisphere and 69.5 % in the non-dominant hemisphere. The mean NIHSS score was 16.0 +/- 5 at admission. The mean length of stay was 22 +/- 17 days. 35 % of patients developed a DVT including 27 % who developed above-knee DVT and required placement of an inferior vena cava filter. In multivariable analysis, predictors of DVT were an NIHSS >= 17 (p = 0.007), seizures (p = 0.003), hypertension (p = 0.03), and increasing length of stay (p = 0.01). The proportion of patients who developed PE was 13 %. In multivariate analysis, BMI >= 30 predicted PE (p = 0.05). CONCLUSIONS: The rate of DVT and PE is remarkably high in patients with large hemispheric infarction undergoing decompressive hemicraniectomy despite prophylactic measures. We recommend routine screening for DVT in this population. Interventions beyond the standard prophylactic measures may be necessary in this high-risk group. PMID- 26896094 TI - Correction: Response to MET Inhibitors in Patients with Stage IV Lung Adenocarcinomas Harboring MET Mutations Causing Exon 14 Skipping. PMID- 26896093 TI - Long-Term Cognitive Deficits After Subarachnoid Hemorrhage in Rats. AB - BACKGROUND: Cognitive dysfunction can be a long-term complication following subarachnoid hemorrhage (SAH). Preclinical models have been variously characterized to emulate this disorder. This study was designed to directly compare long-term cognitive deficits in the context of similar levels of insult severity in the cisterna magna double-blood (DB) injection versus prechiasmatic blood (PB) injection SAH models. METHODS: Pilot work identified blood injectate volumes necessary to provide similar mortality rates (20-25 %). Rats were then randomly assigned to DB or PB insults. Saline injection and naive rats were used as controls. Functional and cognitive outcome was assessed over 35 days. RESULTS: DB and PB caused similar transient rotarod deficits. PB rats exhibited decreased anxiety behavior on the elevated plus maze, while anxiety was increased in DB. DB and PB caused differential deficits in the novel object recognition and novel object location tasks. Morris water maze performance was similarly altered in both models (decreased escape latency and increased swimming speed). SAH caused histologic damage in the medial prefrontal cortex, perirhinal cortex, and hippocampal CA1, although severity of injury in the respective regions differed between DB and PB. CONCLUSION: Both SAH models caused long-term cognitive deficits in the context of similar insult severity. Cognitive deficits differed between the two models, as did distribution of histologic injury. Each model offers unique properties and both models may be useful for study of SAH-induced cognitive deficits. PMID- 26896095 TI - NCI-MATCH Trial Draws Strong Interest. AB - After 800 cancer patients enrolled during the first 3 months of the NCI-MATCH trial, organizers have extended a temporary halt in enrollment to gear up for the next phase. The basket study, which matches patients to approved or experimental drugs based on specific genetic mutations in their tumors, is expected to resume in April or May. PMID- 26896097 TI - Locomotor Recovery in Spinal Cord Injury: Insights Beyond Walking Speed and Distance. AB - Recovery of locomotor function after incomplete spinal cord injury (iSCI) is clinically assessed through walking speed and distance, while improvements in these measures might not be in line with a normalization of gait quality and are, on their own, insensitive at revealing potential mechanisms underlying recovery. The objective of this study was to relate changes of gait parameters to the recovery of walking speed while distinguishing between parameters that rather reflect speed improvements from factors contributing to overall recovery. Kinematic data of 16 iSCI subjects were repeatedly recorded during in-patient rehabilitation. The responsiveness of gait parameters to walking speed was assessed by linear regression. Principal component analysis (PCA) was applied on the multivariate data across time to identify factors that contribute to recovery after iSCI. Parameters of gait cycle and movement dynamics were both responsive and closely related to the recovery of walking speed, which increased by 96%. Multivariate analysis revealed specific gait parameters (intralimb shape normality and consistency) that, although less related to speed increments, loaded highly on principal component one (PC1) (58.6%) explaining the highest proportion of variance (i.e., recovery of outcome over time). Interestingly, measures of hip, knee, and ankle range of motion showed varying degrees of responsiveness (from very high to very low) while not contributing to gait recovery as revealed by PCA. The conjunct application of two analysis methods distinguishes gait parameters that simply reflect increased walking speed from parameters that actually contribute to gait recovery in iSCI. This distinction may be of value for the evaluation of interventions for locomotor recovery. PMID- 26896098 TI - Molecular trophic markers in marine food webs and their potential use for coral ecology. AB - Notable advances in ecological genomics have been driven by high-throughput sequencing technology and taxonomically broad sequence repositories that allow us to accurately assess species interactions with great taxonomic resolution. The use of DNA as a marker for ingested food is particularly relevant to address predator-prey interactions and disentangle complex marine food webs. DNA-based methods benefit from reductionist molecular approaches to address ecosystem scale processes, such as community structure and energy flow across trophic levels, among others. Here we review how molecular trophic markers have been used to better understand trophic interactions in the marine environment and their advantages and limitations. We focus on animal groups where research has been focused, such as marine mammals, seabirds, fishes, pelagic invertebrates and benthic invertebrates, and use case studies to illustrate how DNA-based methods unraveled food-web interactions. The potential of molecular trophic markers for disentangling the complex trophic ecology of corals is also discussed. PMID- 26896096 TI - IFNgamma and CCL2 Cooperate to Redirect Tumor-Infiltrating Monocytes to Degrade Fibrosis and Enhance Chemotherapy Efficacy in Pancreatic Carcinoma. AB - Dense fibrosis and a robust macrophage infiltrate are key therapeutic barriers in pancreatic ductal adenocarcinoma (PDAC). CD40 activation can circumvent these barriers by inducing macrophages, originating from peripheral blood monocytes, to deplete fibrosis. The precise mechanism and therapeutic implications of this antifibrotic activity, though, remain unclear. Here, we report that IFNgamma and CCL2 released systemically in response to a CD40 agonist cooperate to redirect a subset of Ly6C(+)CCR2(+)monocytes/macrophages to infiltrate tumors and deplete fibrosis. Whereas CCL2 is required for Ly6C(+)monocyte/macrophage infiltration, IFNgamma is necessary for tumor-infiltrating monocytes/macrophages to shift the profile of matrix metalloproteinases (MMP) in tumors, leading to MMP-dependent fibrosis degradation. In addition, MMP13-dependent loss of extracellular matrix components induced by a CD40 agonist increased PDAC sensitivity to chemotherapy. Our findings demonstrate that fibrosis in PDAC is a bidirectional process that can be rapidly altered by manipulating a subset of tumor-infiltrating monocytes, leading to enhanced chemotherapy efficacy. SIGNIFICANCE: We report that CD40 agonists improve chemotherapy efficacy in pancreatic carcinoma by redirecting tumor-infiltrating monocytes/macrophages to induce fibrosis degradation that is dependent on MMPs. These findings provide novel insight into the plasticity of monocytes/macrophages in cancer and their capacity to regulate fibrosis and modulate chemotherapy efficacy in pancreatic carcinoma. PMID- 26896099 TI - Embryonic transcriptome of the brackishwater amphipod Gammarus chevreuxi. AB - Environmental change can dramatically alter the development of aquatic organisms. While the effect of such change on physiological and morphological ontogenies is becoming clearer, the molecular mechanisms underpinning them are largely unexplored. Characterizing these mechanisms is often limited by the lack of molecular resources. We have applied Illumina HiSeq sequencing to RNA isolated from different developmental stages of the brackishwater amphipod Gammarus chevreuxi. Over 52.6M paired-end reads were assembled de novo into 172,081 contigs, representing 118,812 potential genes. The assembly generated constitutes a reference embryonic transcriptome for an ecologically-important aquatic shredder species. This resource will contribute to our understanding of the mechanisms underpinning the development of physiological function through functional, comparative and quantitative expression studies. It will also allow the identification of candidate biomarkers for assessing the impact of environmental stressors in estuarine systems. PMID- 26896100 TI - Liver and Other Gastrointestinal Cancers Are Frequent in Mexican Americans. AB - BACKGROUND: Disease patterns in Mexican American health-disparity populations differ from larger US populations. AIMS: This study is aimed to determine frequency of gastrointestinal cancers in Mexican Americans. METHODS: We analyzed self-reported data from the Cameron County Hispanic Cohort where we find high rates of risk factors for cancer: obesity (48.5 %) and diabetes (30.7 %). Participants provided cancer histories about themselves and first- and second degree relatives. Logistic regression models assessed risk factors. Frequencies of cancer sites were ranked and validated using concurrent age local cancer registry data. RESULTS: Among 9,249 individuals (participants and their relatives), there were 1,184 individuals with reports of cancer. Among cohort participants under 70 years of age, the most significant risk factor for all cause cancers was diabetes (OR 3.57, 95 % CI 1.32, 9.62). Participants with metabolic syndrome were significantly more likely to report cancer in relatives [1.73 (95 % CI 1.26, 2.37]. Among cancers in fathers, liver cancer was ranked third, stomach fourth, colorectal sixth, and pancreas tenth. In mothers, stomach was third, liver fourth, colorectal seventh, and pancreas eleventh. The unusual prominence of these cancers in Mexican Americans, including liver cancer, was supported by age-adjusted incidence in local registry data. CONCLUSIONS: Gastrointestinal system cancers, particularly, liver cancer, in a Mexican American health disparity cohort and their relatives rank higher than in other ethnicities and are associated with high rates of diabetes and metabolic syndrome. Effective prevention of diabetes and low-tech, high-quality screening strategies for gastrointestinal cancers are needed in health disparity communities. PMID- 26896101 TI - Racial Differences in Chronic Pain and Quality of Life among Adolescents and Young Adults with Moderate or Severe Hemophilia. AB - BACKGROUND AND OBJECTIVE: We explored racial differences in adherence to recommended clotting factor treatment regimens, chronic pain, and quality of life (QoL) among adolescents and young adults (AYAs) diagnosed with moderate or severe hemophilia. METHODS: A convenience sample of hemophilia patients aged 13-25 years completed an online cross-sectional survey in 2012. Chronic pain was measured using the revised Faces Pain Scale (FPS-R) and dichotomized as high (FPS-R >= 4) or low (FPS-R < 4). QoL was measured with the SF-36. RESULTS: Of 80 AYA participants (79 male), most had severe disease (91 %) and hemophilia A (91 %). Most were white (76 %) and non-Hispanic (88 %). At the univariate level, compared to whites, non-whites were more likely to have produced an inhibitor against clotting factor treatment (74 vs 38 %, p < .01), less likely to have commercial health insurance (16 vs 63 %, p < .001), more likely to report high levels of chronic pain (FPS-R >= 4) (63 vs 26 %, p < .01), and had lower SF-36 physical composite summary (PCS) scores. Adjusted logistic and quantile regression modeling, respectively, revealed that non-whites were 5.31 (95 % CI 1.62, 17.4; p < .01) times more likely to report high chronic pain and had median PCS scores that were 26.0 (95 % CI 11.0, 40.9; p < .01) points lower than whites. CONCLUSIONS: Targeted efforts to prevent and manage chronic pain among non-white AYAs with moderate or severe hemophilia are necessary. After accounting for demographic and clinical differences, there were no racial differences in adherence to recommended clotting factor treatment regimens; however, non-whites were more than five times more likely to report high levels of chronic pain, which predicted worse overall physical QoL, bodily pain, physical and social functioning, and greater role limitations due to physical health. PMID- 26896102 TI - Does Social Context Matter? Income Inequality, Racialized Identity, and Health Among Canada's Aboriginal Peoples Using a Multilevel Approach. AB - OBJECTIVES: Debates surrounding the importance of social context versus individual level processes have a long history in public health. Aboriginal peoples in Canada are very diverse, and the reserve communities in which they reside are complex mixes of various cultural and socioeconomic circumstances. The social forces of these communities are believed to affect health, in addition to individual level determinants, but no large scale work has ever probed their relative effects. One aspect of social context, relative deprivation, as indicated by income inequality, has greatly influenced the social determinants of health landscape. An investigation of relative deprivation in Canada's Aboriginal population has never been conducted. This paper proposes a new model of Aboriginal health, using a multidisciplinary theoretical approach that is multilevel. METHODS: This study explored the self-rated health of respondents using two levels of determinants, contextual and individual. Data were from the 2001 Aboriginal Peoples Survey. There were 18,890 Registered First Nations (subgroup of Aboriginal peoples) on reserve nested within 134 communities. The model was assessed using a hierarchical generalized linear model. RESULTS: There was no significant variation at the contextual level. Subsequently, a sequential logistic regression analysis was run. With the sole exception culture, demographics, lifestyle factors, formal health services, and social support were significant in explaining self-rated health. CONCLUSIONS: The non-significant effect of social context, and by extension relative deprivation, as indicated by income inequality, is noteworthy, and the primary role of individual level processes, including the material conditions, social support, and lifestyle behaviors, on health outcomes is illustrated. It is proposed that social structure is best conceptualized as a dynamic determinant of health inequality and more multilevel theoretical models of Aboriginal health should be developed and tested. PMID- 26896103 TI - Racial Differences in Treatment Decision-Making for Men with Clinically Localized Prostate Cancer: a Population-Based Study. AB - PURPOSE: Racial differences in prostate cancer treatment patterns have motivated concerns about over- and undertreatment. We surveyed black and white patients with localized prostate cancer (LPC) regarding their treatment decision-making processes to gain a better perspective on factors associated with LPC treatment choice. METHODS: We conducted a population-based, cross-sectional survey of 260 men (132 black, 128 white) aged <=75 years, with newly diagnosed LPC. Our primary outcome was treatment choice (either surgery, radiation, or watchful waiting/active surveillance (WW/AS)), and our primary predictors were race and tumor risk level. RESULTS: Overall, treatment choice did not differ by race. As cancer risk increased, both black and white patients were more likely to undergo surgery and less likely to receive radiation. However, the pattern of WW/AS was different between white and black men. White men were less likely to select WW/AS as cancer risk increased, while risk level was unrelated to black men undergoing WW/AS. Urologist's recommendation had the greatest impact on men's treatment choice, followed by tumor risk level, age, and personal preferences. CONCLUSIONS: Although there were no overall racial differences in treatment choice, when stratified by tumor risk level, the pattern of WW/AS was different between white and black patients, suggesting that over- and undertreatment is a larger concern for black than white men. A risk-stratified approach to understand racial disparities in LPC treatment and better strategies to aid black men in their treatment decision-making are needed to reduce racial disparities in prostate cancer outcomes. PMID- 26896104 TI - Racial and Ethnic Disparities in Health and Health Care: an Assessment and Analysis of the Awareness and Perceptions of Public Health Workers Implementing a Statewide Community Transformation Grant in Texas. AB - INTRODUCTION: Little is known about the awareness of public health professionals regarding racial and ethnic disparities in health in the United States of America (USA). Our study objective was to assess the awareness and perceptions of a group of public health workers in Texas regarding racial health disparities and their chief contributing causes. METHODS: We surveyed public health professionals working on a statewide grant in Texas, who were participants at health disparities' training workshops. Multivariable logistic regression was employed in examining the association between the participants' characteristics and their perceptions of the social determinants of health as principal causes of health disparities. RESULTS: There were 106 respondents, of whom 38 and 35 % worked in health departments and non-profit organizations, respectively. The racial/ethnic groups with the highest incidence of HIV/AIDS and hypertension were correctly identified by 63 and 50 % of respondents, respectively, but only 17, and 32 % were knowledgeable regarding diabetes and cancer, respectively. Seventy-one percent of respondents perceived that health disparities are driven by the major axes of the social determinants of health. Exposure to information about racial/ethnic health disparities within the prior year was associated with a higher odds of perceiving that social determinants of health were causes of health disparities (OR 9.62; 95 % CI 2.77, 33.41). CONCLUSION: Among public health workers, recent exposure to information regarding health disparities may be associated with their perceptions of health disparities. Further research is needed to investigate the impact of such exposure on their long-term perception of disparities, as well as the equity of services and programs they administer. PMID- 26896105 TI - Human Papilloma Virus Awareness Among Hispanic Females with Inflammatory Bowel Disease. AB - Women with inflammatory bowel disease (IBD) may be at increased risk of human papilloma virus (HPV) infection and HPV-related malignancies, as many are immunocompromised secondary to the use of immunosuppressant agents. Several studies have addressed the knowledge about cervical cancer risk factors in different populations, particularly HPV infection and its association with cervical malignancies; most of these studies show poor patient knowledge. The purpose of this study is to describe the knowledge of females with IBD about HPV infection and the HPV vaccine. We performed a cross-sectional study in 147 consecutive patients attending the clinics of the University of Puerto Rico Center for IBD from 2009 to 2010. An interviewer-administered questionnaire was used to collect information on demographics, lifestyles, and HPV-related knowledge of participants. Bivariate analysis using the chi-square statistics and Fisher's exact test was used to examine factors associated with HPV awareness. The mean age of participants was 36.6 years (SD = 13.91 years). Three fourth (77 %) of women had awareness of the existence of HPV, and 58 % did know about the existence of HPV vaccines. Among those who had heard about HPV, 79.6 % knew that HPV can cause cervical cancer, and 57.5 % knew that the virus is sexually transmitted. Among those who knew of the vaccine, 75.3 % learned about its existence through the media, while only 15.3 %, through their health-care provider. Only three women within recommended ages (2 %) had been vaccinated against HPV, although 50 % of participants indicated that they would definitely/probably vaccinate against HPV in the future. A significant trend was observed, where more educated women were more likely to have heard of HPV (p for trend = 0.0017). Women who were high school graduates/some college (OR = 6.63, 95 % CI = 1.71-25.66) and those with at least an associate degree (OR = 11.69, 95 % CI = 3.05-45.89) were more likely to be aware of the HPV vaccine than women without a high school degree. Our study documents poor knowledge of HPV and HPV vaccine in this population of IBD patients in Puerto Rico. Although vaccination coverage is low in this population, women are receptive to the possibility of vaccination in the future. Given that this population may be at an increased risk of HPV infection and related morbidities, education and vaccination programs should be promoted among them. PMID- 26896106 TI - Testing of a Model with Latino Patients That Explains the Links Among Patient Perceived Provider Cultural Sensitivity, Language Preference, and Patient Treatment Adherence. AB - INTRODUCTION: Disparities in treatment adherence based on race and ethnicity are well documented but poorly understood. Specifically, the causes of treatment nonadherence among Latino patients living in the USA are complex and include cultural and language barriers. PURPOSE: The purpose of this study was to examine whether patients' perceptions in patient-provider interactions (i.e., trust in provider, patient satisfaction, and patient sense of interpersonal control in patient-provider interactions) mediate any found association between patient perceived provider cultural sensitivity (PCS) and treatment adherence among English-preferred Latino (EPL) and Spanish-preferred Latino (SPL) patients. METHODS: Data from 194 EPL patients and 361 SPL patients were obtained using questionnaires. A series of language-specific structural equation models were conducted to test the relationship between patient-perceived PCS and patient treatment adherence and the examined mediators of this relationship among the Latino patients. RESULTS: No significant direct effects of patient-perceived PCS on general treatment adherence were found. However, as hypothesized, several significant indirect effects emerged. Preferred language appeared to have moderating effects on the relationships between patient-perceived PCS and general treatment adherence. CONCLUSION: These results suggest that interventions to promote treatment adherence among Latino patients should likely include provider training to foster patient-defined PCS, trust in provider, and patient satisfaction with care. Furthermore, this training needs to be customized to be suitable for providing care to Latino patients who prefer speaking Spanish and Latino patients who prefer speaking English. PMID- 26896107 TI - Beliefs and Preferences for Medical Research Among African-Americans. AB - BACKGROUND AND OBJECTIVES: Numerous factors contribute to underrepresentation of African-Americans in medical research, including beliefs, historical events, structural, and health access obstacles. This study examined beliefs about medical research and the types of study methods preferred among potential African American research participants. METHODS: A sample of 304 African-American participants from the Washington, DC Metropolitan area, completed a survey evaluating beliefs about medical research and preferred research study methods. Multiple Regression analyses were performed to examine how age, gender, and education may influence these beliefs and preferences for research study methods. RESULTS: The beliefs and preferences surveyed did not differ by age, gender, or educational attainment. There was an overwhelmingly favorable belief (90 %) that medical research was necessary and assists in finding a cure for a disease. Most respondents preferred participating in research related to issues with which they were familiar (e.g., diabetes, hypertension) or working with researchers of a similar ethnic background to themselves. Interestingly, though nonsignificant, those with higher levels of educational trended toward the belief that participation in research was risky. CONCLUSION: The findings of this study indicate that certain beliefs about medical research participation and preferred study methodologies reported by African-Americans did not differ by age, gender, or level of education. This information about African-American's beliefs and preferences regarding medical research should lead to an awareness of potential gains in African-American participation through the development of culturally sensitive medical research studies and methodologies. PMID- 26896109 TI - Vivir Con Un Corazon Saludable: a Community-Based Educational Program Aimed at Increasing Cardiovascular Health Knowledge in High-Risk Hispanic Women. AB - BACKGROUND: Hispanic women suffer from high rates of cardiometabolic risk factors and an increasingly disproportionate burden of cardiovascular disease (CVD). Particularly, Hispanic women with limited English proficiency suffer from low levels of CVD knowledge associated with adverse CVD health outcomes. METHODS: Thirty-two predominantly Spanish-speaking Hispanic women completed, Vivir Con un Corazon Saludable (VCUCS), a culturally tailored Spanish language-based 6-week intensive community program targeting CVD health knowledge through weekly interactive health sessions. A 30-question CVD knowledge questionnaire was used to assess mean changes in CVD knowledge at baseline and postintervention across five major knowledge domains including CVD epidemiology, dietary knowledge, medical information, risk factors, and heart attack symptoms. RESULTS: Completion of the program was associated with a statistically significant (p < 0.001) increase in total mean CVD knowledge scores from 39 % (mean 11.7/30.0) to 66 % (mean 19.8/30.0) postintervention consistent with a 68 % increase in overall mean CVD scores. There was a statistically significant (p < 0.001) increase in mean knowledge scores across all five CVD domains. CONCLUSION: A culturally tailored Spanish language-based health program is effective in increasing CVD awareness among high CVD risk Hispanic women with low English proficiency and low baseline CVD knowledge. PMID- 26896108 TI - Perceived Safety, Quality and Cultural Competency of Maternity Care for Culturally and Linguistically Diverse Women in Queensland. AB - Various policies, plans and initiatives have been implemented to provide safe, quality and culturally competent care to patients within Queensland's health care system. A series of models of maternity care are available in Queensland that range from standard public care to private midwifery care. The current study aimed to determine whether identifying as culturally or linguistically diverse (CALD) was associated with the perceived safety, quality and cultural competency of maternity care from a consumer perspective, and to identify specific needs and preferences of CALD maternity care consumers. Secondary analysis of data collected in the Having a Baby in Queensland Survey 2012 was used to compare the experiences of 655 CALD women to those of 4049 non-CALD women in Queensland, Australia, across three stages of maternity care: pregnancy, labour and birth, and after birth. After adjustment for model of maternity care received and socio demographic characteristics, CALD women were significantly more likely than non CALD women to experience suboptimal staff technical competence in pregnancy, overall perceived safety in pregnancy and labour/birth, and interpersonal sensitivity in pregnancy and labour/birth. Approximately 50 % of CALD women did not have the choice to use a translator or interpreter, or the gender of their care provider, during labour and birth. Thirteen themes of preferences and needs of CALD maternity care consumers based on ethnicity, cultural beliefs, or traditions were identified; however, these were rarely met. Findings imply that CALD women in Queensland experience disadvantageous maternity care with regards to perceived staff technical competence, safety, and interpersonal sensitivity, and receive care that lacks cultural competence. Improved access to support persons, continuity and choice of carer, and staff availability and training is recommended. PMID- 26896110 TI - Neighborhood Racial and Socioeconomic Disparities in the Food and Alcohol Environment: Are There Differences by Commercial Data Sources? AB - OBJECTIVES: This study examined neighborhood racial and socioeconomic disparities and the density of food and alcohol establishments. We also examined whether these disparities differed by data source. METHODS: This study included commercial data for 2003 and 2009 from InfoUSA and Dun and Bradstreet (D&B) in 416 census tracts in Allegheny County, PA. Food and alcohol establishment densities were calculated by using area and population data from the 2000 US census. Differences between InfoUSA and D&B of food and alcohol densities across neighborhood racial and socioeconomic characteristics were tested using correlations and two-way mixed analysis of variance (ANOVA). RESULTS: There were differences by data source in the association between neighborhood racial and socioeconomic characteristics and food/alcohol establishment density. There was a positive correlation between grocery store/supermarket density and percentage black, poverty, and percentage without a car among D&B data but not in InfoUSA. Alcohol outlet density (AOD) increased as neighborhood poverty increased for both data sources, but the mean difference in AOD between InfoUSA and D&B was highest among neighborhoods with 25-50 % poverty (Cohen's d -0.49, p < 0.001) compared to neighborhoods with lower or higher poverty (2003 data). Mean grocery store density increased as percentage poverty increased, but only among D&B (2009 data). CONCLUSIONS: Differences in commercial data in the location and numeration of food and alcohol establishments are associated with neighborhood racial and socioeconomic characteristics and may introduce biases concerning neighborhood food and alcohol environments, racial and socioeconomic disparities, and health. PMID- 26896111 TI - Racial Disparities in the Pathogenesis of Type 2 Diabetes and its Subtypes in the African Diaspora: A New Paradigm. AB - The global epidemic of diabetes has extended to the developing countries including Sub-Sahara Africa. In this context, blacks with type 2 diabetes in the African Diaspora continue to manifest 1.5-2 times higher prevalent rates than in their white counterparts. Previous studies have demonstrated that blacks with and without type 2 diabetes have alterations in hepatic and peripheral insulin sensitivity, beta-cell function, and hepatic insulin clearance as well as hepatic glucose dysregulation when compared to whites. In addition, non-diabetic blacks in the African Diaspora manifest multiple metabolic mediators that predict type 2 diabetes and its subtypes. These pathogenic modifiers include differences in subclinical inflammation, oxidative stress burden, and adipocytokines in blacks in the African Diaspora prior to clinical diagnosis. Consequently, blacks in the African Diaspora manifest subtypes of type 2 diabetes, including ketosis-prone diabetes and J type diabetes. Given the diversity of type 2 diabetes in blacks in the African Diaspora, we hypothesize that blacks manifest multiple early pathogenic defects prior to the diagnosis of type 2 diabetes and its subtypes. These metabolic alterations have strong genetic component, which appears to play pivotal and primary role in the pathogenesis of type 2 diabetes and its subtypes in blacks in the African Diaspora. However, environmental factors must also be considered as major contributors to the higher prevalence of type 2 diabetes and its subtypes in blacks in the African Diaspora. These multiple alterations should be targets for early prevention of type 2 diabetes in blacks in the African Diaspora. PMID- 26896112 TI - Racial and Ethnic Disparities in Early Childhood Obesity: Growth Trajectories in Body Mass Index. AB - OBJECTIVE: The aims of this study are to describe growth trajectories in the body mass index (BMI) among the major racial and ethnic groups of US children and to identify predictors of children's BMI trajectories. METHODS: The Early Childhood Longitudinal Study-Birth Cohort (ECLS-B) was used to identify predictors of BMI growth trajectories, including child characteristics, maternal attributes, home practices related to diet and social behaviors, and family sociodemographic factors. Growth models, spanning 48 to 72 months of age, were estimated with hierarchical linear modeling via STATA/Xtmixed methods. RESULTS: Approximately one-third of 4-year-old females and males were overweight and/or obese. African American and Latino children displayed higher predicted mean BMI scores and differing mean BMI trajectories, compared with White children, adjusting for time independent and time-dependent predictors. Several factors were significantly associated with lower mean BMI trajectories, including very low birth weight, higher maternal education level, residing in a two-parent household, and breastfeeding during infancy. Greater consumption of soda and fast food was associated with higher mean BMI growth. Soda consumption was a particularly strong predictor of mean BMI growth trajectory for young Black children. Neither the child's inactivity linked to television viewing nor fruit nor vegetable consumption was predictive of BMI growth for any racial/ethnic group. CONCLUSION: Significant racial and ethnic differences are discernible in BMI trajectories among young children. Raising parents' and health practitioners' awareness of how fast food and sweetened-beverage consumption contributes to early obesity and growth in BMI-especially for Blacks and Latinos-could improve the health status of young children. PMID- 26896113 TI - Developing Research and Community Literacies to Recruit Latino Researchers and Practitioners to Address Health Disparities. AB - Engaging community residents and undergraduate Latino students in developing research and community literacies can expose both groups to resources needed to address health disparities. The bidirectional learning process described in this article developed these literacies through an ethnographic mapping fieldwork activity that used a learning-by-doing method in combination with reflection on the research experience. The active efforts of research team members to promote reflection on the research activities were integral for developing research and community literacies. Our findings suggest that, through participating in this field research activity, undergraduate students and community residents developed a better understanding of resources for addressing health disparities. Our research approach assisted community residents and undergraduate students by demystifying research, translating scientific and community knowledge, providing exposure to multiple literacies, and generating increased awareness of research as a tool for change among community residents and their organizations. The commitment of the community and university leadership to this pedagogical method can bring out the full potential of mentoring, both to contribute to the development of the next generation of Latino researchers and to assist community members in their efforts to address health disparities. PMID- 26896114 TI - Racial/Ethnic Differences in Childhood Blood Lead Levels Among Children <72 Months of Age in the United States: a Systematic Review of the Literature. AB - Childhood lead poisoning is a serious public health problem with long-term adverse effects. Healthy People 2020's environmental health objective aims to reduce childhood blood lead levels; however, efforts may be hindered by potential racial/ethnic differences. Recent recommendations have lowered the blood lead reference level. This review examined racial/ethnic differences in blood lead levels among children under 6 years of age. We completed a search of PubMed, CINAHL, and PsycINFO databases for published works from 2002 to 2012. We identified studies that reported blood lead levels and the race/ethnicity of at least two groups. Ten studies met inclusion criteria for the review. Blood lead levels were most frequently reported for black, white, and Hispanic children. Six studies examined levels between blacks, whites, and Hispanics and two between blacks and whites. Studies reporting mean lead levels among black, whites, and Hispanics found that blacks had the highest mean blood lead level. Additionally, studies reporting blood lead ranges found that black children were more likely to have elevated levels. Studies suggest that black children have higher blood lead levels compared to other racial/ethnic groups. Future studies are warranted to obtain ample sample sizes for several racial/ethnic groups to further examine differences in lead levels. PMID- 26896115 TI - Racial Disparities in Sexual Dysfunction Outcomes After Prostate Cancer Treatment: Myth or Reality? AB - Among diverse subject areas in the field of prostate cancer management, treatment related sexual dysfunction complications persist today as a significant potential problem for all men receiving treatment for this disease. The conjecture that African-American men are disproportionately affected by this problem among ethnic groups is not trivial and warrants attention in view of the possibility that its risk profile, whether real or perceived, may influence clinical management decisions impacting survival outcomes in this high-prostate cancer-risk population. A literature review was performed to define the occurrence and significance of sexual dysfunction after prostate cancer treatment in African American men, with an emphasis on clinically localized treatment. Data retrieved from population-based as well as single-center investigations are conflicting with regard to the extent and quality of life relevance of sexual dysfunction following prostate cancer treatments in African-American men, relative to that of ethnically different counterparts. Some reports suggest a relatively greater trend in African-American men than other ethnic groups toward obtaining clinical management for sexual dysfunction and experiencing psychosocial effects from it, lending additional support for the possibly greater effect of this problem in African-American men. Although further studies are needed to define sexual dysfunction after prostate cancer treatment and ascertain its bother and impact on quality of life in African-American men, survivorship care that encompasses sexual dysfunction management should proceed with appropriate attention given to cultural, educational, and psychosocial variables. PMID- 26896116 TI - Perception of Obesity in African-American and Arab-American Minority Groups. AB - BACKGROUND: Effectiveness of health education programs and interventions, designed to improve obesity rates, may vary according to perceptions of health within cultural groups. METHOD: A qualitative approach was used. Two minority cultural groups (Arab-American and African-American) living in the same county were studied to compare perceptions of health, nutrition, and obesity and subsequent health behaviors. RESULTS: Control, expectations, bias, acceptance, and access were the five themes identified. Arab-Americans that had lower weights, lower prevalence of chronic diseases, expected healthy weights, reported age and gender bias related to being overweight were not as accepting of being overweight and did not report difficulties in accessing healthy food choices compared to their African-American counterparts. CONCLUSIONS: Health interventions aimed at reducing obesity rates and related chronic diseases should be culturally specific and aimed at changing expected and accepted cultural norms. Cultural group's void of certain disease states should be studied and used as models to ameliorate the problem in other cultures. Changing health behaviors within a certain cultural group may produce better outcomes when initiated from a member of that same group. The impact of economic and environmental factors on health behaviors must also be considered. PMID- 26896118 TI - Development of a New Adult Sickle Cell Disease Center Within an Academic Cancer Center: Impact on Hospital Utilization Patterns and Care Quality. AB - BACKGROUND: A national shortage of specialized centers with expertise in the management of adults with sickle cell disease (SCD) remains a concerning public health disparity. Yet, there is an abundance of cancer centers whose operational infrastructure is not only suited to the treatment of the oncology patient, but also can provide medical and procedural care essential to the management of the patient with SCD. Our adult SCD center was formally embedded within an academic hospital-based cancer center in 2009. An evaluation of the impact of this new center has been performed. METHODS: A retrospective chart review was conducted of all SCD encounters occurring 5 years pre- and post-SCD center establishment. Demographic, clinical, as well as hospital utilization and care quality data were compared. RESULTS: The SCD population grew from 22 to 165 patients. Following establishment of the SCD center, patients experienced greater average annual outpatient preventative visits for chronic disease management (1 vs. 4.1) and fewer average hospitalizations yearly (2.4 vs. 1). There was a decrease in hospitalization rates for management of acute pain (50 vs. 23 %), average hospitalization length of stay (12 vs. 6 days), and the proportion of hospital discharges resulting in readmission within 30 days (60 vs. 40 %). Hydroxyurea use among eligible patients increased from 30 to 90 %. CONCLUSION: Findings suggest that embedding adult SCD centers within existing cancer centers can positively impact patterns of health care utilization and improve the quality of care. PMID- 26896117 TI - Black:White Disparities in HIV Mortality in the United States: 1990-2009. AB - OBJECTIVES: The aim of this study was to assess whether racial disparities in human immunodeficiency virus (HIV) mortality in the USA have changed over time. METHODS: Using vital records from the National Center for Health Statistics and census data from the US Census Bureau, we calculated the race- and gender specific HIV mortality rates and corresponding racial rate ratios for non Hispanic Blacks and non-Hispanic Whites in the USA for four 5-year increments from 1990-2009. Rates were age-adjusted using the 2000 USA standard population. Additionally, we calculated excess Black deaths for 2005-2009. RESULTS: For the total, male, and female populations, we observed a statistically significant increase in the Black:White HIV mortality disparity between T1 (1990-1994) and T4 (2005-2009). The increasing disparity was due to the fact that the decrease in mortality rates from T1 to T4 was greater among Whites than Blacks. This disparity led to 5603 excess Black deaths in the USA at T4. CONCLUSIONS: Previous research suggests that as HIV becomes more treatable, racial disparities widen, as observed in this study for both men and women. Existing disparities could be ameliorated if access to care were equal among these groups. Equal access would enable more individuals to achieve viral suppression, the final step of the HIV Care Continuum. PMID- 26896119 TI - The Challenge and Benefit of the Inclusion of Race in Medical School Education. PMID- 26896121 TI - The Positive Outlook Study: A Randomised Controlled Trial Evaluating Online Self Management for HIV Positive Gay Men. AB - The aim of this paper was to evaluate the effectiveness of an online self management program in improving health outcomes and well-being for gay men living with HIV in Australia. The online Positive Outlook Program was based on self efficacy theory and used a self-management approach to enhance HIV-positive gay men's skills, confidence and abilities to manage the psychosocial issues associated with HIV in daily life. The 7-week program was delivered in closed groups and comprised information modules, action-planning activities, moderated discussion boards, and weekly peer-facilitated 'live chats'. A randomised controlled trial was conducted to establish the effectiveness of the Positive Outlook program compared to a 'usual care' control. Participants were HIV positive gay men 18 years or older living in Australia. Primary outcomes were evaluated at three time-points (baseline, post-intervention and 12-week's post intervention follow-up) and included HIV-related quality of life (PROQOL-HIV), outcomes of health education (HeiQ) and HIV specific self-efficacy (Positive Outlook Self-Efficacy Scale). A total of 132 gay men with HIV in Australia were randomly allocated to the intervention (n = 68) or usual care control (n = 64) groups. Maximum likelihood marginal-linear modelling indicated significant improvement in the intervention group on the PROQOL-HIV subscales of body change (p = 0.036), social relationships (p = 0.035) and emotional distress (p = 0.031); the HeiQ subscales of health-directed activity (p = 0.048); constructive attitudes and approaches (p = 0.015); skill and technique acquisition (p = 0.046) and health service navigation (p = 0.008); and the Positive Outlook Self-Efficacy Scale on the subscales of relationships (p = 0.019); social participation (p = 0.006); and emotions (p = 0.041). Online delivery of self-management programs is feasible and has the potential to improve quality of life, self-management skills and domain specific self-efficacy for gay men with HIV. PMID- 26896120 TI - Roles of Self-Stigma, Social Support, and Positive and Negative Affects as Determinants of Depressive Symptoms Among HIV Infected Men who have Sex with Men in China. AB - Poor mental health was prevalent among HIV positive men who have sex with men (HIVMSM), and a tremendous burden extents on their families and society. The present study investigated the prevalence of depression and its relationship with social support, HIV self-stigma, positive affect and negative affect among 321 HIVMSM in Chengdu, China. The study was conducted during July 2013 through October 2013. Findings showed that 55.8 % of the participants had mild to severe depression. The results of structural equation modeling showed that social support and positive affect were negatively associated with depression, while HIV self-stigma and negative affect were positively associated with depression. Social support, positive affect, and negative affect mediated the association between HIV self-stigma and depression. The hypothesized model had a satisfactory fit. Interventions improving mental health among this population are warranted. PMID- 26896122 TI - Long-Term Comparison of Simultaneous Topography-Guided Photorefractive Keratectomy Followed by Corneal Cross-linking versus Corneal Cross-linking Alone. AB - PURPOSE: To compare the results of corneal collagen cross-linking (CXL) alone with combined simultaneous topography-guided photorefractive keratectomy plus CXL (tPRK-CXL) for progressive keratoconus for a 3-year interval. DESIGN: Prospective, comparative interventional case series. PARTICIPANTS: Forty-eight patients (60 eyes) with progressive keratoconus. METHODS: Thirty eyes underwent combined tPRK with a solid-state laser (maximum ablation depth, 50 MUm) followed by CXL, and 30 eyes underwent CXL alone. Groups were matched in terms of age and keratoconus stage. MAIN OUTCOME MEASURES: Corrected distance visual acuity (CDVA), uncorrected distance visual acuity (UDVA), keratometry, and corneal confocal microscopy. RESULTS: Mean follow up was 39+/-11 months. Mean age at operation was 28+/-5.82 years. Before surgery, average CDVA in the tPRK-CXL group was 0.26+/-0.17 logarithm of the minimum angle of resolution (logMAR), and in the CXL group was 0.24+/-0.18 logMAR (P = 0.58). At last follow-up, CDVA was 0.09+/ 0.10 logMAR in the tPRK-CXL group and 0.15+/-0.12 logMAR in the CXL group (P < 0.05). In both groups, no patient lost more than 2 lines of Snellen visual acuity, whereas 19 eyes and 8 eyes in the tPRK-CXL group and in the CXL group, respectively, gained 2 or more lines of CDVA. Before surgery, average UDVA was 0.83+/-0.54 logMAR in the tPRK-CXL group and 0.86+/-0.62 logMAR in the CXL group (P = 0.79). At last follow-up, UDVA was 0.27+/-0.25 logMAR in the tPRK-CXL group and 0.69+/-0.58 logMAR in the CXL group (P < 0.001). Before surgery, steep and flat keratometry had no significant differences between groups, and at last follow-up, both steep and flat keratometry readings were significantly flatter in the tPRK-CXL group compared with the CXL group. Depth of CXL treatment, as evaluated by confocal microscopy, was 269.8+/-31.8 MUm in the CXL group and 299.7+/-29.8 MUm in the tPRK-CXL group (P < 0.001). No differences were found in endothelial cell density. CONCLUSIONS: Simultaneous tPRK followed by CXL in this series of keratoconus patients offered significantly improved vision to treated patients in comparison with CXL alone, and similar results regarding postoperative stability. Safety concerns regarding corneal thickness were taken into account in treatment planning. PMID- 26896123 TI - Incidence of Age-Related Macular Degeneration in a Multi-Ethnic United States Population: The Multi-Ethnic Study of Atherosclerosis. AB - PURPOSE: To describe the incidence of age-related macular degeneration (AMD) and associated risk factors in 4 racial/ethnic groups (white, black, Hispanic, and Chinese) residing in the United States. DESIGN: Prospective cohort study. PARTICIPANTS: A total of 3811 participants, aged 46 to 86 years, from the Multi Ethnic Study of Atherosclerosis (MESA) cohort, with retinal data collected twice, on average, 8 years apart. METHODS: Fundus images, taken using a digital camera through dark-adapted pupils using a standard protocol and the same equipment at both study visits, were graded centrally for early and late AMD on the basis of drusen size, type and area, increased retinal pigment, retinal pigment epithelial depigmentation, neovascular lesions, and geographic atrophy using the modified Wisconsin Age-Related Maculopathy Grading System. Demographic, clinical, and laboratory measures were included in multivariable regression models to determine their impact on the variation in AMD incidence among racial/ethnic groups. MAIN OUTCOME MEASURES: Incident early and late AMD. RESULTS: The overall 8-year age- and sex-standardized incidence of early and late AMD were 4.1% and 2.3%, respectively, with incidence of early and late AMD highest in whites (5.3% and 4.1%, respectively), intermediate in Chinese (4.5% and 2.2%, respectively) and Hispanics (3.3% and 0.8%, respectively), and lowest in blacks (1.6% and 0.4%, respectively). By adjusting for age and sex, blacks had a 70% lower risk of developing early AMD than whites, and this decreased only slightly to a 67% lower risk after multivariable adjustment. By adjusting for age, sex, and race/ethnicity, hyperopia was associated with early AMD (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.04-2.20), as was astigmatism (OR, 1.47; 95% CI, 1.00-2.16), but not myopia (P = 0.29). Age, race/ethnicity, current smoking, hyperopia, and AMD-susceptibility genotypes Complement Factor H (CFH) RS1061170 and Age Related Maculopathy Susceptibility 2 (ARMS2) RS3793917 were independently associated with incident early AMD in multivariable models for the combined sample. However, the only statistically significant factor consistently associated with incident early AMD across the 4 racial/ethnic groups was increasing age. Risk factors for late AMD were not assessed because of its low incidence, particularly across racial/ethnic groups. CONCLUSIONS: Variation in the incidence of early AMD exists among racial/ethnic groups in the United States and is not explained by the clinical, genetic, and environmental factors included in this study. PMID- 26896126 TI - Ultra-widefield Imaging of the Peripheral Retinal Vasculature in Normal Subjects. AB - PURPOSE: To establish the extent of the peripheral retinal vasculature in normal eyes using ultra-widefield (UWF) fluorescein angiography. DESIGN: Prospective, observational study. PARTICIPANTS: Fifty-nine eyes of 31 normal subjects, stratified by age, with no evidence of ocular disease in either eye by history and ophthalmoscopic examination. METHODS: Ultra-widefield fluorescein angiographic images were captured centrally and with peripheral steering using the Optos 200Tx (Optos, Dunfermline, United Kingdom). Images obtained at different gaze angles were montaged and corrected for peripheral distortion using a stereographic projection method to provide a single image for grading of the peripheral edge of the visible vasculature. The border of the vascularized retina was expressed as a radial surface distance from the center of the optic disc. The vascularized area was calculated based on this mean peripheral border position for each quadrant. MAIN OUTCOME MEASURES: Mean distance (mm) from the center of optic disc to the peripheral vascular border. RESULTS: In normal eyes, the mean radial surface distance from the center of the optic disc to the peripheral edge of the visible vasculature was 20.3+/-1.4 mm and the mean area of normal perfused retina was 977.0 mm(2). There was no significant difference between right and left eyes or between male and female participants. However, the distance to the periphery differed depending on the quadrant, with temporal (22.5+/-0.9 mm) being larger than inferior (20.4+/-1.7 mm) being larger than superior (19.2+/-1.5 mm) being larger than nasal (17.4+/-0.9 mm; P < 0.001) for all interquadrant comparisons. Interestingly, the distances to the perfused vascular border were significantly shorter in older individuals (>=60 years) than in younger subjects. CONCLUSIONS: Ultra-widefield fluorescein angiography is an important tool for studying the extent of peripheral retinal vasculature. With the increasing use of UWF imaging to evaluate and manage patients with retinal vascular disease, the normative data from this study may provide a useful reference when assessing the pathologic significance of findings in the setting of disease. PMID- 26896124 TI - Individualized Ranibizumab Regimen Driven by Stabilization Criteria for Central Retinal Vein Occlusion: Twelve-Month Results of the CRYSTAL Study. AB - PURPOSE: To assess the 12-month efficacy and safety profile of an individualized regimen of ranibizumab 0.5 mg driven by stabilization criteria in patients with macular edema secondary to central retinal vein occlusion (CRVO). DESIGN: A 24 month, prospective, open-label, single-arm, multicenter study. PARTICIPANTS: Three hundred fifty-seven patients. METHODS: Patients were treated with monthly ranibizumab 0.5-mg injections (minimum of 3 injections) until stable visual acuity (VA) was maintained for 3 consecutive months. Thereafter, ranibizumab 0.5 mg was dosed as needed if monthly monitoring indicated a loss of VA resulting from disease activity. MAIN OUTCOME MEASURES: Mean change from baseline at month 12 in best-corrected VA (BCVA; primary end point) and safety over 12 months. The efficacy of this regimen in subgroups categorized by baseline BCVA score, CRVO duration, or presence of macular ischemia (exploratory analysis). RESULTS: At baseline, the mean BCVA was 53.0 letters and mean CRVO duration was 8.9 months (median, 2.4 months). Ranibizumab 0.5-mg treatment resulted in a statistically significant mean gain in BCVA from baseline at month 12 of 12.3 letters (standard deviation [SD], 16.72 letters; P < 0.0001). The mean number of ranibizumab injections up to month 12 was 8.1 (SD, 2.77). At month 12, mean BCVA gains were similar with or without macular ischemia at baseline (11.6 vs. 12.1 letters); the mean BCVA gain was higher with baseline CRVO duration of less than 3 months (13.4 letters) than with a longer duration (>=3-<9 months, 11.1 letters; >=9 months, 10.9 letters). Patients with lower baseline BCVA had larger mean BCVA gains at month 12 than those with higher baseline BCVA (<=39/40-59/>=60 and 18.0/12.7/8.9 letters, respectively), although the absolute BCVA at month 12 was higher with higher baseline BCVA. No new ocular or nonocular safety events were observed. CONCLUSIONS: An individualized dosing regimen of ranibizumab 0.5 mg driven by stabilization criteria for up to 12 months resulted in significant BCVA gain in a broad population of patients with macular edema secondary to CRVO, including those with macular ischemia at baseline. The safety findings were consistent with those reported in previous ranibizumab studies in patients with CRVO. PMID- 26896125 TI - Simple Limbal Epithelial Transplantation: Long-Term Clinical Outcomes in 125 Cases of Unilateral Chronic Ocular Surface Burns. AB - PURPOSE: This study describes the long-term clinical outcomes of autologous simple limbal epithelial transplantation (SLET), a relatively new technique of limbal stem cell transplantation. DESIGN: This was a single-center prospective interventional cases series. PARTICIPANTS: This study included 125 patients, 65 adults and 60 children who developed unilateral limbal stem cell deficiency (LSCD) after suffering with ocular surface burns and underwent SLET between 2010 and 2014. METHODS: A 1-clock hour limbal biopsy sample was obtained from the unaffected eye. At the same sitting, the recipient eye was surgically prepared and the donor tissue was divided into small pieces and transplanted using an amniotic membrane scaffold with fibrin glue. MAIN OUTCOME MEASURES: The diagnosis and outcome in every case was validated by 5 independent masked assessors. The primary outcome measure was restoration of a completely epithelized, stable, and avascular corneal surface. The secondary outcome measure was improvement in visual acuity. Complications, risk factors for failure, and immunohistochemistry analysis of corneas that underwent SLET also were described. RESULTS: At a median postoperative follow-up of 1.5 years (range, 1-4 years), 95 of 125 eyes (76%; 95% confidence interval, 68.5%-83.5%) maintained a successful outcome. Kaplan-Meier analysis revealed a comparable survival probability at 1 year of 80% in adults and 72% in children (P = 0.304). Two-line improvement in visual acuity was seen in 75.2%, and 67% of successful cases attained 20/60 or better vision (P < 0.0001). Progressive conjunctivalization occurred in 18.4% of eyes. The clinical factors associated with failure were identified as acid injury, severe symblepharon, SLET combined with keratoplasty, and postoperative loss of transplants (P <= 0.0075). Success rates were comparable among faculty and trainees (P = 0.71). Immunohistochemistry revealed successful regeneration of normal corneal epithelium (CK3(+)/12(+)) without admixture of conjunctiva cells (Muc5AC(-)/CK19(-)) and replenishment of limbal stem cell (DeltaNp63alpha(+)/ABCG2(+)) reserve. CONCLUSIONS: Autologous SLET is an effective, reliable and replicable technique for long-lasting corneal regeneration and vision restoration in unilateral chronic ocular surface burns. Simple limbal epithelial transplantation is probably preferable to other techniques of limbal stem cell transplantation, particularly where cell cultivation facilities are unavailable. PMID- 26896127 TI - Illuminating Anaerobic Microbial Community and Cooccurrence Patterns across a Quality Gradient in Chinese Liquor Fermentation Pit Muds. AB - Fermentation pit mud, an important reservoir of diverse anaerobic microorganisms, is essential for Chinese strong-aroma liquor production. Pit mud quality, according to its sensory characteristics, can be divided into three grades: degraded, normal, and high quality. However, the relationship between pit mud microbial community and pit mud quality is poorly understood, as are microbial associations within the pit mud ecosystem. Here, microbial communities at these grades were compared using Illumina MiSeq sequencing of the variable region V4 of the 16S rRNA gene. Our results revealed that the pit mud microbial community was correlated with its quality and environmental factors. Species richness, biodiversity, and relative and/or absolute abundances of Clostridia,Clostridium kluyveri, Bacteroidia, and Methanobacteria significantly increased, with corresponding increases in levels of pH, NH4 (+), and available phosphorus, from degraded to high-quality pit muds, while levels of Lactobacillus, dissolved organic carbon, and lactate significantly decreased, with normal samples in between. Furthermore, 271 pairs of significant and robust correlations (cooccurrence and negative) were identified from 76 genera using network analysis. Thirteen hubs of cooccurrence patterns, mainly under the Clostridia,Bacteroidia,Methanobacteria, and Methanomicrobia, may play important roles in pit mud ecosystem stability, which may be destroyed with rapidly increased levels of lactic acid bacteria (Lactobacillus,Pediococcus, and Streptococcus). This study may help clarify the relationships among microbial community, environmental conditions, and pit mud quality, allow the improvement of pit mud quality by using bioaugmentation and controlling environmental factors, and shed more light on the ecological rules guiding community assembly in pit mud. PMID- 26896128 TI - Cell Culture Isolation of Piscine Nodavirus (Betanodavirus) in Fish-Rearing Seawater. AB - Piscine nodavirus (betanodavirus) is the causative agent of viral nervous necrosis (VNN) in a variety of cultured fish species, particularly marine fish. In the present study, we developed a sensitive method for cell culture isolation of the virus from seawater and applied the method to a spontaneous fish-rearing environment. The virus in seawater was concentrated by an iron-based flocculation method and subjected to isolation with E-11 cells. A real-time reverse transcriptase PCR (RT-PCR) assay was used to quantify the virus in water. After spiking into seawater was performed, a betanodavirus strain (red spotted grouper nervous necrosis virus [RGNNV] genotype) was effectively recovered in the E-11 cells at a detection limit of approximately 10(5)copies (equivalent to 10(2)50% tissue culture infective doses [TCID50])/liter seawater. In an experimental infection of juvenile sevenband grouper (Epinephelus septemfasciatus) with the virus, the virus was isolated from the drainage of a fish-rearing tank when the virus level in water was at least approximately 10(5)copies/liter. The application of this method to seven band grouper-rearing floating net pens, where VNN prevailed, resulted in the successful isolation of the virus from seawater. No differences were found in the partial sequences of the coat protein gene (RNA2) between the clinical virus isolates of dead fish and the cell-cultured virus isolates from seawater, and the viruses were identified as RGNNV. The infection experiment showed that the virus isolates from seawater were virulent to seven band grouper. These results showed direct evidence of the horizontal transmission of betanodavirus via rearing water in marine aquaculture. PMID- 26896129 TI - Chemical Synthesis and In Vitro Evaluation of a Phage Display-Derived Peptide Active against Infectious Salmon Anemia Virus. AB - Infectious salmon anemia virus (ISAV) is the etiological agent of the disease by the same name and causes major losses in the salmon industry worldwide. Epizootic ISAV outbreaks have occurred in Norway and, to a lesser degree, in Canada. In 2007, an ISAV outbreak in Chile destroyed most of the seasonal production and endangered the entire Chilean salmon industry. None of the existing prophylactic approaches have demonstrated efficacy in providing absolute protection from or even a palliative effect on ISAV proliferation. Sanitary control measures for ISAV, based on molecular epidemiology data, have proven insufficient, mainly due to high salmon culture densities and a constant presence of a nonpathogenic strain of the virus. This report describes an alternative treatment approach based on interfering peptides selected from a phage display library. The screening of a phage display heptapeptide library resulted in the selection of a novel peptide with significant in vitro antiviral activity against ISAV. This peptide specifically interacted with the viral hemagglutinin-esterase protein, thereby impairing virus binding, with plaque reduction assays showing a significant reduction in viral yields. The identified peptide acts at micromolar concentrations against at least two different pathogenic strains of the virus, without detectable cytotoxic effects on the tested fish cells. Therefore, antiviral peptides represent a novel alternative for controlling ISAV and, potentially, other fish pathogens. IMPORTANCE: Identifying novel methods for the efficient control of infectious diseases is imperative for the future of global aquaculture. The present study used a phage display heptapeptide library to identify a peptide with interfering activity against a key protein of the infectious salmon anemia virus (ISAV). A piscine orthomyxovirus, ISAV is a continuous threat to the commercial sustainability of cultured salmon production worldwide. The complex epidemiological strategy of this pathogen has made prophylactic control extremely difficult. The identified antiviral peptide efficiently impairs ISAV infection in vitro by specifically blocking hemagglutinin-esterase, a pivotal surface protein of this virus. Peptide synthesis could further modify the primary structure of the identified peptide to improve specific activity and stability. The present results form the foundation for developing a new pharmacological treatment against ISAV. PMID- 26896131 TI - Oxidation of Molecular Hydrogen by a Chemolithoautotrophic Beggiatoa Strain. AB - A chemolithoautotrophic strain of the family Beggiatoaceae, Beggiatoa sp. strain 35Flor, was found to oxidize molecular hydrogen when grown in a medium with diffusional gradients of oxygen, sulfide, and hydrogen. Microsensor profiles and rate measurements suggested that the strain oxidized hydrogen aerobically when oxygen was available, while hydrogen consumption under anoxic conditions was presumably driven by sulfur respiration.Beggiatoa sp. 35Flor reached significantly higher biomass in hydrogen-supplemented oxygen-sulfide gradient media, but hydrogen did not support growth of the strain in the absence of reduced sulfur compounds. Nevertheless, hydrogen oxidation can provide Beggiatoa sp. 35Flor with energy for maintenance and assimilatory purposes and may support the disposal of internally stored sulfur to prevent physical damage resulting from excessive sulfur accumulation. Our knowledge about the exposure of natural populations of Beggiatoa ceae to hydrogen is very limited, but significant amounts of hydrogen could be provided by nitrogen fixation, fermentation, and geochemical processes in several of their typical habitats such as photosynthetic microbial mats and submarine sites of hydrothermal fluid flow. IMPORTANCE: Reduced sulfur compounds are certainly the main electron donors for chemolithoautotrophic Beggiatoa ceae, but the traditional focus on this topic has left other possible inorganic electron donors largely unexplored. In this paper, we provide evidence that hydrogen oxidation has the potential to strengthen the ecophysiological plasticity of Beggiatoa ceaein several ways. Moreover, we show that hydrogen oxidation by members of this family can significantly influence biogeochemical gradients and therefore should be considered in environmental studies. PMID- 26896130 TI - Functional Metagenomics of a Biostimulated Petroleum-Contaminated Soil Reveals an Extraordinary Diversity of Extradiol Dioxygenases. AB - A metagenomic library of a petroleum-contaminated soil was constructed in a fosmid vector that allowed heterologous expression of metagenomic DNA. The library, consisting of 6.5 Gb of metagenomic DNA, was screened for extradiol dioxygenase (Edo) activity using catechol and 2,3-dihydroxybiphenyl as the substrates. Fifty-eight independent clones encoding extradiol dioxygenase activity were identified. Forty-one different Edo-encoding genes were identified. The population of Edo genes was not dominated by a particular gene or by highly similar genes; rather, the genes had an even distribution and high diversity. Phylogenetic analyses revealed that most of the genes could not be ascribed to previously defined subfamilies of Edos. Rather, the Edo genes led to the definition of 10 new subfamilies of type I Edos. Phylogenetic analysis of type II enzymes defined 7 families, 2 of which harbored the type II Edos that were found in this work. Particularly striking was the diversity found in family I.3 Edos; 15 out of the 17 sequences assigned to this family belonged to 7 newly defined subfamilies. A strong bias was found that depended on the substrate used for the screening: catechol mainly led to the detection of Edos belonging to the I.2 family, while 2,3-dihydroxybiphenyl led to the detection of most other Edos. Members of the I.2 family showed a clear substrate preference for monocyclic substrates, while those from the I.3 family showed a broader substrate range and high activity toward 2,3-dihydroxybiphenyl. This metagenomic analysis has substantially increased our knowledge of the existing biodiversity of Edos. PMID- 26896133 TI - Evaluation of a Parchment Document, the 13th Century Incorporation Charter for the City of Krakow, Poland, for Microbial Hazards. AB - The literature of environmental microbiology broadly discusses issues associated with microbial hazards in archives, but these publications are mainly devoted to paper documents. There are few articles on historical parchment documents, which used to be very important for the development of literature and the art of writing. These studies present a broad spectrum of methods for the assessment of biodeterioration hazards of the parchment document in question. They are based on both conventional microbiological methods and advanced techniques of molecular biology. Here, a qualitative analysis was conducted, based on genetic identification of bacteria and fungi present on the document as well as denaturing gradient gel electrophoresis profiling and examining the destructive potential of isolated microbes. Moreover, the study involved a quantitative and qualitative microbiological assessment of the indoor air in the room where the parchment was kept. The microbes with the highest destructive potential that were isolated from the investigated item were Bacillus cereus and Acinetobacter lwoffii bacteria and Penicillium chrysogenum,Chaetomium globosum, and Trichoderma longibrachiatum fungi. The presence of the B. cereuss train was particularly interesting since, under appropriate conditions, it leads to complete parchment degradation within several days. PMID- 26896132 TI - Engineering Escherichia coli for Microbial Production of Butanone. AB - To expand the chemical and molecular diversity of biotransformation using whole cell biocatalysts, we genetically engineered a pathway in Escherichia coli for heterologous production of butanone, an important commodity ketone. First, a 1 propanol-producing E. coli host strain with its sleeping beauty mutase (Sbm) operon being activated was used to increase the pool of propionyl-coenzyme A (propionyl-CoA). Subsequently, molecular heterofusion of propionyl-CoA and acetyl CoA was conducted to yield 3-ketovaleryl-CoA via a CoA-dependent elongation pathway. Lastly, 3-ketovaleryl-CoA was channeled into the clostridial acetone formation pathway for thioester hydrolysis and subsequent decarboxylation to form butanone. Biochemical, genetic, and metabolic factors affecting relative levels of ketogenesis, acidogenesis, and alcohol genesis under selected fermentative culture conditions were investigated. Using the engineered E. coli strain for batch cultivation with 30 g liter(-1)glycerol as the carbon source, we achieved coproduction of 1.3 g liter(-1)butanone and 2.9 g liter(-1)acetone. The results suggest that approximately 42% of spent glycerol was utilized for ketone biosynthesis, and thus they demonstrate potential industrial applicability of this microbial platform. PMID- 26896134 TI - Identifying Potential Mechanisms Enabling Acidophily in the Ammonia-Oxidizing Archaeon "Candidatus Nitrosotalea devanaterra". AB - Ammonia oxidation is the first and rate-limiting step in nitrification and is dominated by two distinct groups of microorganisms in soil: ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB). AOA are often more abundant than AOB and dominate activity in acid soils. The mechanism of ammonia oxidation under acidic conditions has been a long-standing paradox. While high rates of ammonia oxidation are frequently measured in acid soils, cultivated ammonia oxidizers grew only at near-neutral pH when grown in standard laboratory culture. Although a number of mechanisms have been demonstrated to enable neutrophilic AOB growth at low pH in the laboratory, these have not been demonstrated in soil, and the recent cultivation of the obligately acidophilic ammonia oxidizer "Candidatus Nitrosotalea devanaterra" provides a more parsimonious explanation for the observed high rates of activity. Analysis of the sequenced genome, transcriptional activity, and lipid content of "Ca Nitrosotalea devanaterra" reveals that previously proposed mechanisms used by AOB for growth at low pH are not essential for archaeal ammonia oxidation in acidic environments. Instead, the genome indicates that "Ca Nitrosotalea devanaterra" contains genes encoding both a predicted high-affinity substrate acquisition system and potential pH homeostasis mechanisms absent in neutrophilic AOA. Analysis of mRNA revealed that candidate genes encoding the proposed homeostasis mechanisms were all expressed during acidophilic growth, and lipid profiling by high-performance liquid chromatography-mass spectrometry (HPLC-MS) demonstrated that the membrane lipids of "Ca Nitrosotalea devanaterra" were not dominated by crenarchaeol, as found in neutrophilic AOA. This study for the first time describes a genome of an obligately acidophilic ammonia oxidizer and identifies potential mechanisms enabling this unique phenotype for future biochemical characterization. PMID- 26896136 TI - A Tale of Transmission: Aeromonas veronii Activity within Leech-Exuded Mucus. AB - Transmission, critical to the establishment and persistence of host-associated microbiotas, also exposes symbionts to new environmental conditions. With horizontal transmission, these different conditions represent major lifestyle shifts. Yet genome-wide analyses of how microbes adjust their transcriptomes toward these dramatic shifts remain understudied. Here, we provide a comprehensive and comparative analysis of the global transcriptional profiles of a symbiont as it shifts between lifestyles during transmission. The gammaproteobacterium Aeromonas veronii is transmitted from the gut of the medicinal leech to other hosts via host mucosal castings, yet A. veronii can also transition from mucosal habitancy to a free-living lifestyle. These three lifestyles are characterized by distinct physiological constraints and consequently lifestyle-specific changes in the expression of stress-response genes. Mucus-bound A. veronii had the greatest expression in terms of both the number of loci and levels of transcription of stress-response mechanisms. However, these bacteria are still capable of proliferating within the mucus, suggesting the availability of nutrients within this environment. We found that A. veronii alters transcription of loci in a synthetic pathway that obtains and incorporates N-acetylglucosamine (NAG; a major component of mucus) into the bacterial cell wall, enabling proliferation. Our results demonstrate that symbionts undergo dramatic local adaptation, demonstrated by widespread transcriptional changes, throughout the process of transmission that allows them to thrive while they encounter new environments which further shape their ecology and evolution. PMID- 26896135 TI - Metagenomic Analyses of the Autotrophic Fe(II)-Oxidizing, Nitrate-Reducing Enrichment Culture KS. AB - Nitrate-dependent ferrous iron [Fe(II)] oxidation (NDFO) is a well-recognized chemolithotrophic pathway in anoxic sediments. The neutrophilic chemolithoautotrophic enrichment culture KS originally obtained from a freshwater sediment (K. L. Straub, M. Benz, B. Schink, and F. Widdel, Appl Environ Microbiol 62:1458-1460, 1996) has been used as a model system to study NDFO. However, the primary Fe(II) oxidizer in this culture has not been isolated, despite extensive efforts to do so. Here, we present a metagenomic analysis of this enrichment culture in order to gain insight into electron transfer pathways and the roles of different bacteria in the culture. We obtained a near-complete genome of the primary Fe(II) oxidizer, a species in the family Gallionellaceae, and draft genomes from its flanking community members. A search of the putative extracellular electron transfer pathways in these genomes led to the identification of a homolog of the MtoAB complex [a porin-multiheme cytochromec system identified in neutrophilic microaerobic Fe(II)-oxidizing Sideroxydans lithotrophicus ES-1] in a Gallionellaceae sp., and findings of other putative genes involving cytochromecand multicopper oxidases, such as Cyc2 and OmpB. Genome-enabled metabolic reconstruction revealed that this Gallionellaceae sp. lacks nitric oxide and nitrous oxide reductase genes and may partner with flanking populations capable of complete denitrification to avoid toxic metabolite accumulation, which may explain its resistance to growth in pure culture. This and other revealed interspecies interactions and metabolic interdependencies in nitrogen and carbon metabolisms may allow these organisms to cooperate effectively to achieve robust chemolithoautotrophic NDFO. Overall, the results significantly expand our knowledge of NDFO and suggest a range of genetic targets for further exploration. PMID- 26896138 TI - Effect of Dietary Oxalate on the Gut Microbiota of the Mammalian Herbivore Neotoma albigula. AB - Diet is one of the primary drivers that sculpts the form and function of the mammalian gut microbiota. However, the enormous taxonomic and metabolic diversity held within the gut microbiota makes it difficult to isolate specific diet microbe interactions. The objective of the current study was to elucidate interactions between the gut microbiota of the mammalian herbivore Neotoma albigula and dietary oxalate, a plant secondary compound (PSC) degraded exclusively by the gut microbiota. We quantified oxalate degradation in N. albigula fed increasing amounts of oxalate over time and tracked the response of the fecal microbiota using high-throughput sequencing. The amount of oxalate degraded in vivo was linearly correlated with the amount of oxalate consumed. The addition of dietary oxalate was found to impact microbial species diversity by increasing the representation of certain taxa, some of which are known to be capable of degrading oxalate (e.g., Oxalobacter spp.). Furthermore, the relative abundances of 117 operational taxonomic units (OTU) exhibited a significant correlation with oxalate consumption. The results of this study indicate that dietary oxalate induces complex interactions within the gut microbiota that include an increase in the relative abundance of a community of bacteria that may contribute either directly or indirectly to oxalate degradation in mammalian herbivores. PMID- 26896137 TI - Estimates of Soil Bacterial Ribosome Content and Diversity Are Significantly Affected by the Nucleic Acid Extraction Method Employed. AB - Modern sequencing technologies allow high-resolution analyses of total and potentially active soil microbial communities based on their DNA and RNA, respectively. In the present study, quantitative PCR and 454 pyrosequencing were used to evaluate the effects of different extraction methods on the abundance and diversity of 16S rRNA genes and transcripts recovered from three different types of soils (leptosol, stagnosol, and gleysol). The quality and yield of nucleic acids varied considerably with respect to both the applied extraction method and the analyzed type of soil. The bacterial ribosome content (calculated as the ratio of 16S rRNA transcripts to 16S rRNA genes) can serve as an indicator of the potential activity of bacterial cells and differed by 2 orders of magnitude between nucleic acid extracts obtained by the various extraction methods. Depending on the extraction method, the relative abundances of dominant soil taxa, in particular Actino bacteria and Proteobacteria, varied by a factor of up to 10. Through this systematic approach, the present study allows guidelines to be deduced for the selection of the appropriate extraction protocol according to the specific soil properties, the nucleic acid of interest, and the target organisms. PMID- 26896139 TI - Dominant Tree Species and Soil Type Affect the Fungal Community Structure in a Boreal Peatland Forest. AB - Boreal peatlands play a crucial role in global carbon cycling, acting as an important carbon reservoir. However, little information is available on how peatland microbial communities are influenced by natural variability or human induced disturbances. In this study, we have investigated the fungal diversity and community structure of both the organic soil layer and buried wood in boreal forest soils using high-throughput sequencing of the internal transcribed spacer (ITS) region. We have also compared the fungal communities during the primary colonization of wood with those of the surrounding soils. A permutational multivariate analysis of variance (PERMANOVA) confirmed that the community composition significantly differed between soil types (P< 0.001) and tree species (P< 0.001). The distance-based linear models analysis showed that environmental variables were significantly correlated with community structure (P< 0.04). The availability of soil nutrients (Ca [P= 0.002], Fe [P= 0.003], and P [P= 0.003]) within the site was an important factor in the fungal community composition. The species richness in wood was significantly lower than in the corresponding soil (P< 0.004). The results of the molecular identification were supplemented by fruiting body surveys. Seven of the genera of Agaricomycotina identified in our surveys were among the top 20 genera observed in pyrosequencing data. Our study is the first, to our knowledge, fungal high-throughput next-generation sequencing study performed on peatlands; it further provides a baseline for the investigation of the dynamics of the fungal community in the boreal peatlands. PMID- 26896140 TI - Mechanisms of Bacterial (Serratia marcescens) Attachment to, Migration along, and Killing of Fungal Hyphae. AB - We have found a remarkable capacity for the ubiquitous Gram-negative rod bacterium Serratia marcescens to migrate along and kill the mycelia of zygomycete molds. This migration was restricted to zygomycete molds and several basidiomycete species. No migration was seen on any molds of the phylum Ascomycota. S. marcescens migration did not require fungal viability or surrounding growth medium, as bacteria migrated along aerial hyphae as well.S. marcescens did not exhibit growth tropism toward zygomycete mycelium. Bacterial migration along hyphae proceeded only when the hyphae grew into the bacterial colony. S. marcescens cells initially migrated along the hyphae, forming attached microcolonies that grew and coalesced to generate a biofilm that covered and killed the mycelium. Flagellum-defective strains of S. marcescens were able to migrate along zygomycete hyphae, although they were significantly slower than the wild-type strain and were delayed in fungal killing. Bacterial attachment to the mycelium does not necessitate type 1 fimbrial adhesion, since mutants defective in this adhesin migrated equally well as or faster than the wild-type strain. Killing does not depend on the secretion of S. marcescens chitinases, as mutants in which all three chitinase genes were deleted retained wild-type killing abilities. A better understanding of the mechanisms by which S. marcescens binds to, spreads on, and kills fungal hyphae might serve as an excellent model system for such interactions in general; fungal killing could be employed in agricultural fungal biocontrol. PMID- 26896142 TI - Lactococcus lactis LMG2081 Produces Two Bacteriocins, a Nonlantibiotic and a Novel Lantibiotic. AB - Bacteriocin producers normally possess dedicated immunity systems to protect themselves from their own bacteriocins.Lactococcus lactis strains LMG2081 and BGBM50 are known as lactococcin G producers. However, BGBM50 was sensitive to LMG2081, which indicated that LMG2081 might produce additional bacteriocins that are not present in BGBM50. Therefore, whole-genome sequencing of the two strains was performed, and a lantibiotic operon (called lctLMG) was identified in LMG2081 but not in BGBM50. The lctLMG operon contains six open reading frames; the first three genes,lmgA ,lmgM, and lmgT, are involved in the biosynthesis and export of bacteriocin, while the other three genes,lmgF,lmgE, and lmgG, are involved in lantibiotic immunity. Mutational analysis confirmed that the lctLMG operon is responsible for the additional antimicrobial activity. Specifically, site directed mutation within this operon rendered LMG2081 inactive toward BGBM50. Subsequent purification and electrospray ionization-time of flight mass spectrometric analysis confirmed that the lantibiotic bacteriocin called lacticin LMG is exported as a 25-amino-acid peptide. Lacticin LMG is highly similar to the lacticin 481 group. It is interesting that a bacteriocin producer produces two different classes of bacteriocins, whose operons are located in the chromosome and a plasmid. PMID- 26896144 TI - Invited Commentary for "0 + 5 Vascular Surgery Residents' Operative Experience in General Surgery: An Analysis of Operative Logs From 12 Integrated Programs". PMID- 26896141 TI - Diversity, Productivity, and Stability of an Industrial Microbial Ecosystem. AB - Managing ecosystems to maintain biodiversity may be one approach to ensuring their dynamic stability, productivity, and delivery of vital services. The applicability of this approach to industrial ecosystems that harness the metabolic activities of microbes has been proposed but has never been tested at relevant scales. We used a tag-sequencing approach with bacterial small subunit rRNA (16S) genes and eukaryotic internal transcribed spacer 2 (ITS2) to measuring the taxonomic composition and diversity of bacteria and eukaryotes in an open pond managed for bioenergy production by microalgae over a year. Periods of high eukaryotic diversity were associated with high and more-stable biomass productivity. In addition, bacterial diversity and eukaryotic diversity were inversely correlated over time, possibly due to their opposite responses to temperature. The results indicate that maintaining diverse communities may be essential to engineering stable and productive bioenergy ecosystems using microorganisms. PMID- 26896143 TI - Complementary Microorganisms in Highly Corrosive Biofilms from an Offshore Oil Production Facility. AB - Offshore oil production facilities are frequently victims of internal piping corrosion, potentially leading to human and environmental risks and significant economic losses. Microbially influenced corrosion (MIC) is believed to be an important factor in this major problem for the petroleum industry. However, knowledge of the microbial communities and metabolic processes leading to corrosion is still limited. Therefore, the microbial communities from three anaerobic biofilms recovered from the inside of a steel pipe exhibiting high corrosion rates, iron oxide deposits, and substantial amounts of sulfur, which are characteristic of MIC, were analyzed in detail. Bacterial and archaeal community structures were investigated by automated ribosomal intergenic spacer analysis, multigenic (16S rRNA and functional genes) high-throughput Illumina MiSeq sequencing, and quantitative PCR analysis. The microbial community analysis indicated that bacteria, particularly Desulfovibrio species, dominated the biofilm microbial communities. However, other bacteria, such as Pelobacter, Pseudomonas, and Geotoga, as well as various methanogenic archaea, previously detected in oil facilities were also detected. The microbial taxa and functional genes identified suggested that the biofilm communities harbored the potential for a number of different but complementary metabolic processes and that MIC in oil facilities likely involves a range of microbial metabolisms such as sulfate, iron, and elemental sulfur reduction. Furthermore, extreme corrosion leading to leakage and exposure of the biofilms to the external environment modify the microbial community structure by promoting the growth of aerobic hydrocarbon degrading organisms. PMID- 26896145 TI - Development and Early Piloting of a CanMEDS Competency-Based Feedback Tool for Surgical Grand Rounds. AB - OBJECTIVE: Grand rounds offer an excellent opportunity for the evaluation of medical expertise, and other competencies, such as communication and professionalism. The purpose of this study was to develop a tool that would facilitate the provision of formative feedback for grand rounds to improve learning. The resulting CanMEDS-based evaluation tool was piloted in an academic surgical department. DESIGN: This study employed the use of a 3-phase, qualitatively-focused, embedded mixed methods approach. In Phase 1, an intrinsic case study was conducted to identify preliminary themes. These findings were crystallized using a quantitative survey. Following interpretation of these data, a grand rounds evaluation tool was developed in Phase 2. The tool was piloted in the Phase 3 focus group. SETTING: This study was piloted at an academic surgical center among members of the Department of Surgery, McMaster University, Ontario, Canada. PARTICIPANTS: Purposive sampling was used for this study. A total of n = 7 individuals participated in the Phase 1 interviews, and n = 24 participants completed the Phase 1 survey. Participants included a representative sample of medical students, residents, fellows, and staff. The tool was piloted among n = 19 participants. RESULTS: The proposed evaluation tool contains 13 Likert-scale questions and 2 open-ended questions. The tool outlines specific questions to assess grand rounds presenters within the structure of the 7 CanMEDS competency domains. "Evaluation fatigue" was identified as a major barrier in the willingness to provide effective feedback. Further, a number of factors regarding the preferred content, structure, and format of surgical grand rounds were identified. CONCLUSIONS: This pilot study presents a CanMEDS-specific evaluation tool that can be applied to surgical grand rounds. With the increasing adoption of competency-based medical education, comprehensive evaluation of surgical activities is required. This form provides a template for the development of competency-based evaluation tools for medical and surgical learning activities. PMID- 26896146 TI - The First 100 Years of American College of Surgeons Presidential Addresses. AB - INTRODUCTION: We reviewed the first 100 years of presidential addresses delivered at the fall congress of the American College of Surgeons (ACS). Our hypothesis was that these addresses would be an excellent indicator of the College's position on surgical policy, ethics, methods, and education. METHODS: All ACS presidential addresses from 1913 to 2013 were identified through the ACS archives website. This included the presenter, title, year, and citation if published in a peer reviewed journal. The text of each address was obtained from the ACS archives, or from the listed citations. Addresses were then classified into 1 of 6 subgroups based on content-surgical credo, medical innovation, medical education, surgical history, business and legal, and personal tribute. The 100 year period was divided into 5 interval each of 20-year and the frequency of each category was graphed over time. RESULTS: There were 111 ACS presidential addresses delivered in the study period. Distribution by category was surgical credo (57%), surgical history (14%), medical innovation (10%), medical education (8%), business and legal (6%), and personal tributes (5%). The frequency of surgical credo has remained stable over time. Business and legal emerged as a new category in 1975. The other topics had low, but stable frequency. CONCLUSION: ACS presidential addresses do reflect the College's position on surgical policy and practice. The college has remained consistent in serving its members, maintaining, and defining the role of its organization, the qualifications for membership, and the expectations for the professional conduct of its members. PMID- 26896148 TI - Efficacy of a Continuous Performance Test Based on Virtual Reality in the Diagnosis of ADHD and Its Clinical Presentations. AB - OBJECTIVE: To analyze the diagnostic effectiveness of the AULA Nesplora test to discriminate the different ADHD presentations: impulsive/hyperactive (I/H), inattentive, and combined. METHOD: A total of 117 students (76.9% male and 23.1% female) between 5 and 16 years of age ( M = 11.18 years, SD = 3.10 years) participated, and were divided into three groups with ADHD according to their presentation, and a control group. RESULTS: Each of the test conditions allowed the discrimination between the I/H and combined presentations with respect to the control group, and between the I/H and inattentive presentations. However, differences among ADHD presentations were only evident when the results were separately analyzed for the visual and auditory modalities. CONCLUSION: This study showed that the indicators offered by the AULA Nesplora test (omissions, commissions, response times, and motor activity) make it possible to establish a differential diagnosis of ADHD presentations when analyzed under different contextual conditions. PMID- 26896147 TI - Task-Level vs. Segment-Level Quantitative Metrics for Surgical Skill Assessment. AB - OBJECTIVE: Task-level metrics of time and motion efficiency are valid measures of surgical technical skill. Metrics may be computed for segments (maneuvers and gestures) within a task after hierarchical task decomposition. Our objective was to compare task-level and segment (maneuver and gesture)-level metrics for surgical technical skill assessment. DESIGN: Our analyses include predictive modeling using data from a prospective cohort study. We used a hierarchical semantic vocabulary to segment a simple surgical task of passing a needle across an incision and tying a surgeon's knot into maneuvers and gestures. We computed time, path length, and movements for the task, maneuvers, and gestures using tool motion data. We fit logistic regression models to predict experience-based skill using the quantitative metrics. We compared the area under a receiver operating characteristic curve (AUC) for task-level, maneuver-level, and gesture-level models. SETTING: Robotic surgical skills training laboratory. PARTICIPANTS: In total, 4 faculty surgeons with experience in robotic surgery and 14 trainee surgeons with no or minimal experience in robotic surgery. RESULTS: Experts performed the task in shorter time (49.74s; 95% CI = 43.27-56.21 vs. 81.97; 95% CI = 69.71-94.22), with shorter path length (1.63m; 95% CI = 1.49-1.76 vs. 2.23; 95% CI = 1.91-2.56), and with fewer movements (429.25; 95% CI = 383.80-474.70 vs. 728.69; 95% CI = 631.84-825.54) than novices. Experts differed from novices on metrics for individual maneuvers and gestures. The AUCs were 0.79; 95% CI = 0.62 0.97 for task-level models, 0.78; 95% CI = 0.6-0.96 for maneuver-level models, and 0.7; 95% CI = 0.44-0.97 for gesture-level models. There was no statistically significant difference in AUC between task-level and maneuver-level (p = 0.7) or gesture-level models (p = 0.17). CONCLUSIONS: Maneuver-level and gesture-level metrics are discriminative of surgical skill and can be used to provide targeted feedback to surgical trainees. PMID- 26896149 TI - Sensory Gating Capacity and Attentional Function in Adults With ADHD: A Preliminary Neurophysiological and Neuropsychological Study. AB - OBJECTIVE: The inability to filter sensory input correctly may impair higher cognitive function in ADHD. However, this relationship remains largely elusive. The objectives of the present study is to investigate the relationship between sensory input processing and cognitive function in adult patients with ADHD. METHOD: This study investigated the relationship between deficit in sensory gating capacity (P50 amplitude changes in a double-click conditioning-testing paradigm and perceptual abnormalities related to sensory gating deficit with the Sensory Gating Inventory [SGI]) and attentional and executive function (P300 amplitude in an oddball paradigm and attentional and executive performances with a neuropsychological test) in 24 adult patients with ADHD. RESULTS: The lower the sensory gating capacity of the brain and the higher the distractibility related to sensory gating inability that the patients reported, the lower the P300 amplitude. CONCLUSION: The capacity of the brain to gate the response to irrelevant incoming sensory input may be a fundamental protective mechanism that prevents the flooding of higher brain structures with irrelevant information in adult patients with ADHD. PMID- 26896150 TI - Differentiation of Body Fluid Stains on Fabrics Using External Reflection Fourier Transform Infrared Spectroscopy (FT-IR) and Chemometrics. AB - Body fluids are evidence of great forensic interest due to the DNA extracted from them, which allows genetic identification of people. This study focuses on the discrimination among semen, vaginal fluid, and urine stains (main fluids in sexual crimes) placed on different colored cotton fabrics by external reflection Fourier transform infrared spectroscopy (FT-IR) combined with chemometrics. Semen vaginal fluid mixtures and potential false positive substances commonly found in daily life such as soaps, milk, juices, and lotions were also studied. Results demonstrated that the IR spectral signature obtained for each body fluid allowed its identification and the correct classification of unknown stains by means of principal component analysis (PCA) and soft independent modeling of class analogy (SIMCA). Interestingly, results proved that these IR spectra did not show any bands due to the color of the fabric and no substance of those present in daily life which were analyzed, provided a false positive. PMID- 26896151 TI - No benefit of extended mesenteric resection with central vascular ligation in right-sided colon cancer. AB - AIM: The optimal extent of mesenteric resection in colon cancer surgery is not known. We have previously shown an increased mortality associated with wider mesenteric resection in right hemicolectomy. This study compares the short- and long-term outcome in three variations of right hemicolectomy based on the position of the vascular ligature in the mesentery. METHOD: In all, 2084 cases of cancer in the caecum or ascending colon were identified in the Swedish Colorectal Cancer Registry and categorized according to the position of the vascular ligature: central ligation of ileocolic vessels (ICVs) +/- right colic vessels (n = 390), central ligation of ICVs + right branch of middle colic vessels (MCVs) (n = 1360) and central ligation of ICVs + central ligation of MCVs (n = 334). RESULTS: Neither 3-year overall survival, 3-year disease-free survival nor local recurrence rate differed between the groups (P = 0.604; P = 0.247; P = 0.237). There was still no difference after multivariate analysis adjusted for age, sex, American Society of Anesthesiologists classification, TNM stage and adjuvant therapy. An increased peri-operative mortality, however, was observed in extended mesenteric resections, increasing from 0.8% in non-extended to 3.6% in more extended resection, P = 0.025. CONCLUSION: The study showed no survival benefit by more extended mesenteric resection, indicating that there is no need to extend the mesenteric resection to involve the MCVs in cancer of the caecum or ascending colon. On the contrary, increased peri-operative mortality by more extensive mesenteric resection was noted suggesting that a more conservative approach may be favourable. PMID- 26896152 TI - Critical incidents, including cardiac arrest, associated with pediatric anesthesia at a tertiary teaching children's hospital. AB - BACKGROUND: Analysis of critical incidents provides valuable information to improve the quality and safety of patient care. This study identified and analyzed pediatric anesthesia-related critical incidents including cardiac arrests in a tertiary teaching children's hospital. METHODS: All pediatric anesthesia-related critical incidents reported in a voluntary departmental reporting system between January 2008 and August 2013 were included in the analysis. A critical incident was defined as (i) any incident that altered patients' vital signs and affected the management of patients while they were under the care of an anesthesiologist, and (ii) human factor: where patient injury or accidents were as a result of human error. Changes in vital signs that recovered spontaneously were excluded. RESULTS: During the 6-year study period, a total of 229 critical incidents were reported from 49,373 anesthetic procedures. The most frequently reported incidents were associated with the respiratory system (55%), with tracheal tube-related events accounting for 40.9% of respiratory incidents followed by laryngospasm (17.3% of respiratory incidents). Cardiac arrest occurred in 42 cases in this study (8.5 cases per 10,000 anesthetics). Cardiovascular problems were the major causes of cardiac arrest (66.7%), and incidents of cardiogenic shock and hemorrhage/hypotension contributed equally to the cardiac arrest induced by cardiovascular problems (each 16.7%). Human factor-related events accounted for 58.5% of all critical incidents of which 53.7% were respiratory events. CONCLUSION: Despite recent improvements in safety of pediatric anesthesia, many preventable factors still remain that can lead to critical incidents. PMID- 26896153 TI - The validity and reliability of the EValuation of INtervention Scale: preliminary report. AB - AIM: Pain management is a priority for infants receiving neonatal care as they undergo many necessary painful and stressful interventions, which are associated with negative short- or long-term consequences. This study aims to validate the content, and test the reliability, of the EValuation of INtervention Scale (EVIN), which is designed to evaluate the use of widely recommended nonpharmacological strategies to reduce neonatal pain and stress during procedures. METHODS: The content of the EVIN was validated with multidisciplinary participation (N = 80), and consistency was established via observations on preterm infants (N = 12, at 31-34 weeks' gestation) during interventions in a neonatal unit. A revised scale was tested for inter-rater reliability with observations of invasive (blood sampling, N = 16) and noninvasive (nappy change, N = 18) interventions. The intraclass correlation coefficient (ICC) was used to determine inter-rater reliability. SPSS (PASW Statistics) version 18 was used for analysis. RESULTS: Very good intraclass correlation coefficients (>0.8) for both invasive (0.962) and noninvasive procedures (0.970) were achieved. CONCLUSION: These results indicate that the EVIN is suitable for the evaluation of nonpharmacological support during painful or stressful interventions. PMID- 26896156 TI - Gianotti-Crosti Syndrome and Erythema Nodosum: Two Distinct Entities or Two Manifestations of the Same Infection? PMID- 26896155 TI - Complement C5 controls liver lipid profile, promotes liver homeostasis and inflammation in C57BL/6 genetic background. AB - Innate immunity contributes effectively to the development of alcoholic liver disease (ALD). In special, the activation of the complement system is involved in the pathogenesis of this disease. Here we investigated the contribution of complement C5 protein to the establishment and maintenance of ALD. Eight- to ten week-old B6C5(+) and B6C5(-) male mice were fed with high fat diet (HFD) only or the same diet containing equicaloric supplements of ethanol (HFDE) or maltodextrin (HFDM) for 10 weeks. Serum parameters of liver function as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AP), albumin, glucose, triglycerides (TG) and cholesterol were evaluated. Liver tissue samples were collected for histopathological analysis, lipid extraction (TG and cholesterol), cytokines (TNF-alpha, IL-6, IL-1beta, IL-10, IL-12, IL-17, IFN-gamma, TGF-beta) measurement and NO production. We observed that B6C5(-) mice HFDE-fed accumulated more liver cholesterol and TG, increased liver IL-17 and IL 10 levels and reduced liver TGF-beta levels when compared to HFD-fed mice. We also observed that serum AST, AP and albumin were increased in B6C5(-) mice. Liver IL-1beta, IL-6, IL-12 and IFN-gamma were decreased in B6C5(-) mice independently of diet. We conclude that C5 acts in the control of serum TG and cholesterol, liver cholesterol deposition, liver homeostasis and C5 promotes a pro-inflammatory liver environment in our mouse model of ALD. PMID- 26896154 TI - Genetic analysis of intestinal polyp development in Collaborative Cross mice carrying the Apc (Min/+) mutation. AB - BACKGROUND: Colorectal cancer is an abnormal tissue development in the colon or rectum. Most of CRCs develop due to somatic mutations, while only a small proportion is caused by inherited mutations. Familial adenomatous polyposis is an inherited genetic disease, which is characterized by colorectal polyps. It is caused by inactivating mutations in the Adenomatous polyposis coli gene. Mice carrying and non-sense mutation in Adenomatous polyposis coli gene at site R850, which designated Apc (R850X/+) (Min), develop intestinal adenomas, while the bulk of the disease is in the small intestine. A number of genetic modifier loci of Min have been mapped, but so far most of the underlying genes have not been identified. In our previous studies, we have shown that Collaborative Cross mice are a powerful tool for mapping loci responsible for phenotypic variation. As a first step towards identification of novel modifiers of Min, we assessed the phenotypic variation between 27 F1 crosses between different Collaborative cross mice and C57BL/6-Min lines. RESULTS: Here, C57BL/6-Min male mice were mated with females from 27 Collaborative cross lines. F1 offspring were terminated at 23 weeks old and multiple phenotypes were collected: polyp counts, intestine length, intestine weight, packed cell volume and spleen weight. Additionally, in eight selected F1 Collaborative cross-C57BL/6-Min lines, body weight was monitored and compared to control mice carry wildtype Adenomatous polyposis coli gene. We found significant (p < 0.05) phenotypic variation between the 27 F1 Collaborative cross C57BL/6-Min lines for all the tested phenotypes, and sex differences with traits; Colon, body weight and intestine length phenotypes, only. Heritability calculation showed that these phenotypes are mainly controlled by genetic factors. CONCLUSIONS: Variation in polyp development is controlled, an appreciable extent, by genetic factors segregating in the Collaborative cross population and suggests that it is suited for identifying modifier genes associated with Apc (Min/+) mutation, after assessing sufficient number of lines for quantitative trait loci analysis. PMID- 26896157 TI - A Diagnostic Algorithm for Children with Low Alkaline Phosphatase Activities: Lessons Learned from Laboratory Screening for Hypophosphatasia. AB - OBJECTIVES: To explore the role of laboratory screening for hypophosphatasia and propose a diagnostic pathway for children with low serum alkaline phosphatase (ALP) activities. STUDY DESIGN: A retrospective hospital-based study over an 8 year period was conducted to identify children younger than 16 years of age with low ALP activity (<100 U/L). Study-positive patients were contacted for repeat sampling, and those with persistently low ALP had plasma pyridoxal-5'-phosphate and urinary phosphoethanolamine measured. RESULTS: Of 323 064 analyzed samples, 1526 had ALP activities <100 U/L. Most patients had transient hypophosphatasemia. Of 50 patients with last-recorded ALP <100 U/L, 32 were excluded given previous ALP >100 U/L. Eighteen were identified as study-positive. Of the 15 surviving children, 13 were traceable. Four had persistently low ALP activity on retesting, of whom 2 had raised pyridoxal-5'-phosphate and phosphoethanolamine concentrations and were subsequently tested for ALPL gene mutations; a 4-year-old asymptomatic girl with a novel homozygous ALPL missense mutation and a 23-year old female with a heterozygous mutation. There was significant overlap in ALP activities between study-positive and 11 current patients with hypophosphatasia. We propose a diagnostic algorithm for children with low ALP activities based on clinical and biochemical variables. CONCLUSIONS: Patients with persistently low ALP activity require further clinical, biochemical, and radiological assessment for hypophosphatasia, even in the absence of clinical symptoms. The proposed diagnostic algorithm for children with low ALP will facilitate early detection of cases of hypophosphatasia, which, with the availability of enzyme replacement for hypophosphatasia, can be life-saving or avoid years of undiagnosed morbidity. PMID- 26896158 TI - Impaired Neurodevelopmental Outcomes in Very Preterm Infants: Much Too Easy to Blame It Just on Morphine! PMID- 26896159 TI - Application of microorganisms in concrete: a promising sustainable strategy to improve concrete durability. AB - The beneficial effect of microbially induced carbonate precipitation on building materials has been gradually disclosed in the last decade. After the first applications of on historical stones, promising results were obtained with the respect of improved durability. An extensive study then followed on the application of this environmentally friendly and compatible material on a currently widely used construction material, concrete. This review is focused on the discussion of the impact of the two main applications, bacterial surface treatment and bacteria based crack repair, on concrete durability. Special attention was paid to the choice of suitable bacteria and the metabolic pathway aiming at their functionality in concrete environment. Interactions between bacterial cells and cementitious matrix were also elaborated. Furthermore, recommendations to improve the effectiveness of bacterial treatment are provided. Limitations of current studies, updated applications and future application perspectives are shortly outlined. PMID- 26896160 TI - Prognostic value of the bone scan index using a computer-aided diagnosis system for bone scans in hormone-naive prostate cancer patients with bone metastases. AB - BACKGROUND: The bone scan index (BSI) using a computer-aided diagnosis system for bone scans is expected to be an objective and quantitative clinical tool for evaluating bone metastatic prostate cancer. This study aimed to evaluate the pretreatment BSI as a prognostic factor in hormone-naive prostate cancer patients with bone metastases. METHODS: The study included 60 patients with hormone-naive, bone metastatic prostate cancer that was initially treated with combined androgen blockade therapy. The BONENAVI system was used for calculating the BSI. We evaluated the correlation between overall survival (OS) and pretreatment clinicopathological characteristics, including patients' age, initial prostate specific antigen (PSA) value, Gleason scores, clinical TNM stage, and the BSI. Cox proportional hazards regression models were used for statistical analysis. RESULTS: The median follow-up duration was 21.4 months. Clinical or PSA progression occurred in 37 (61.7%) patients and 18 (30.0%) received docetaxel. Death occurred in 16 (26.7%) patients. Of these deaths, 15 (25.0%) were due to prostate cancer. The median OS was not reached. In multivariate analysis, age and the BSI were independent prognostic factors for OS. We evaluated the discriminatory ability of our models, including or excluding BSI by quantifying the C-index. The BSI improved the C-index from 0.751 to 0.801 for OS. Median OS was not reached in patients with a BSI <= 1.9 and median OS was 34.8 months in patients with a BSI >1.9 (p = 0.039). CONCLUSIONS: The pretreatment BSI and patients' age are independent prognostic factors for patients with hormone-naive, bone metastatic prostate cancer. PMID- 26896161 TI - Recent decline of DDTs among several organochlorine pesticides in background air in East Asia. AB - Hexachlorocyclohexanes (HCHs), chlordanes (CHLs), and dichlorodiphenyltrichloroethanes (DDTs) in air-mass outflows from East Asia were recorded monthly from April 2009 to March 2014 at Cape Hedo in Japan. These organochlorine pesticides (OCPs) were collected by a high volume air sampler equipped with a quartz fiber filter, a polyurethane foam plug, and activated carbon fiber and analyzed by using a gas chromatograph-high resolution mass spectrometer. The overall (and geometric mean +/- SD) concentration over the period was 4.9-43 pg m(-3) (15 +/- 7.8 pg m(-3)) in HCHs (sum of alpha-/beta /gamma-/delta-HCH), 1.5-83 pg m(-3) (8.8 +/- 11 pg m(-3)) in CHLs (sum of cis /trans-chlordane, cis-/trans-nonachlor, and oxychlordane), and 0.71-16 pg m(-3) (2.5 +/- 2.0 pg m(-3)) in DDTs (sum of o,p'-/p,p'-DDD, o,p'-/p,p'-DDE, and o,p' /p,p'-DDT). Clear seasonal changes, i.e. higher in summer and lower in winter, were observed in HCHs and CHLs, suggesting the dominant effect of temperature dependence, secondary sources in these OCPs. DDT concentration as well as the ratio of (o,p'-DDT + p,p'-DDT) to total DDTs, on the other hand, showed clear a declining trend during the five year sampling period, suggesting the decrease of input of newly produced DDTs in the regional environment by reflecting recent activities in the East Asian region to eliminate production and use of DDTs under the Stockholm Convention. PMID- 26896164 TI - Outstanding JASMS Manuscript Reviewers, 2014-2015. PMID- 26896163 TI - Nicotine Enhances High-Fat Diet-Induced Oxidative Stress in the Kidney. AB - INTRODUCTION: Life expectancy of an obese smoker is 13 years less than a normal weight smoker, which could be linked to the increased renal risk imposed by smoking. Both smoking-through nicotine (NIC)-and obesity-by free fatty acid overload-provoke oxidative stress in the kidney, which ultimately results in development of chronic kidney injury. Their combined renal risk, however, is virtually unknown. We tested the hypothesis that chronic NIC exposure worsens renal oxidative stress in mice on high-fat diet (HFD) by altering the balance between expression of pro-oxidant and antioxidant genes. METHODS: Nine-week-old male C57Bl/6J mice consumed normal diet (ND) or HFD and received either NIC (200 MUg/ml) or vehicle (2% saccharine) in their drinking water. Body weight, plasma clinical parameters, renal lipid deposition, markers of renal oxidative stress and injury, as well as renal expression of the pro-oxidant p66shc and the antioxidant MnSOD were determined after 12 weeks. RESULTS: NIC significantly augmented levels of circulating free fatty acid, as well as lipid deposition, oxidative stress and sublethal injury in the kidneys of mice on HFD. In addition, NIC exposure suppressed HFD-mediated induction of MnSOD while increased expression of p66shc in the kidney. CONCLUSIONS: Tobacco smoking or the increasingly popular E-cigarettes-via NIC exposure-could worsen obesity associated lipotoxicity in the kidney. Hence, our findings could help to develop strategies that mitigate adverse effects of NIC on the obese kidney. IMPLICATIONS: Life expectancy of an obese smoker is 13 years less than a normal weight smoker, which could be linked to the increased renal risk imposed by smoking. NIC-the main component of tobacco smoke, E-cigarettes and replacement therapies-links smoking to renal injury via oxidative stress, which could superimpose renal oxidative stress caused by obesity. Our results substantiate this scenario using a mouse model of diet induced obesity and NIC exposure and imply the augmented long-term renal risk in obese smokers. Also, our study may help to develop strategies that mitigate adverse effects of NIC on the obese kidney. PMID- 26896162 TI - Risk Profiles of Youth Single, Dual, and Poly Tobacco Users. AB - INTRODUCTION: Given widespread availability and uptake of myriad tobacco products among youth, a comprehensive tobacco control agenda necessitates an in-depth exploration of the phenomenon of concurrent tobacco use. METHODS: Multinomial logistic regression generated distinct concurrent tobacco use risk profiles of single, dual, and poly use, defined as use of only one, only two, and any three or more tobacco products in the last 30 days, from the 2012 National Youth Tobacco Survey (n = 24 658). RESULTS: Among youth using tobacco in the past 30 days (n = 5030), the majority were poly tobacco product users (55.9%, n = 2813), followed by single (28.4%, n = 1406), and dual users (16.1%, n = 811). Multivariable models showed higher levels of nicotine dependence among poly users compared to single (relative risk ratio [RRR] = 3.14, P < .001) and dual users (RRR = 2.48, P < .001). Poly users were less likely to express quit intent compared to single (RRR = 0.68, P < .01) or dual users (RRR = 0.77, P < .05). Tobacco harm perceptions were more likely among dual users relative to single product users (RRR = 1.54, P < .05); poly users were less likely to perceive harm (RRR = 0.56, P < .001). Racial and gender differences also emerged. CONCLUSION: As the number of tobacco products increased, nicotine dependence and perceived tobacco use among peers increased, whereas quit intentions decreased. Dual users had greater tobacco harm perceptions than poly and single users and higher prevalence of electronic cigarette use. Results suggest that poly use may be driven by addiction whereas dual use may be motivated by intentions to quit. Focused risk assessments may inform tailored interventions for distinct types of tobacco users. IMPLICATIONS: This study provides an in-depth look at the risks for concurrent tobacco use among youth by creating unique risk profiles for single, dual and poly use. Results from this study can inform tailored interventions for distinct types of tobacco users. PMID- 26896165 TI - Spatial distribution and cluster analysis of retail drug shop characteristics and antimalarial behaviors as reported by private medicine retailers in western Kenya: informing future interventions. AB - BACKGROUND: Efforts to improve malaria case management in sub-Saharan Africa have shifted focus to private antimalarial retailers to increase access to appropriate treatment. Demands to decrease intervention cost while increasing efficacy requires interventions tailored to geographic regions with demonstrated need. Cluster analysis presents an opportunity to meet this demand, but has not been applied to the retail sector or antimalarial retailer behaviors. This research conducted cluster analysis on medicine retailer behaviors in Kenya, to improve malaria case management and inform future interventions. METHODS: Ninety-seven surveys were collected from medicine retailers working in the Webuye Health and Demographic Surveillance Site. Survey items included retailer training, education, antimalarial drug knowledge, recommending behavior, sales, and shop characteristics, and were analyzed using Kulldorff's spatial scan statistic. The Bernoulli purely spatial model for binomial data was used, comparing cases to controls. Statistical significance of found clusters was tested with a likelihood ratio test, using the null hypothesis of no clustering, and a p value based on 999 Monte Carlo simulations. The null hypothesis was rejected with p values of 0.05 or less. RESULTS: A statistically significant cluster of fewer than expected pharmacy-trained retailers was found (RR = .09, p = .001) when compared to the expected random distribution. Drug recommending behavior also yielded a statistically significant cluster, with fewer than expected retailers recommending the correct antimalarial medication to adults (RR = .018, p = .01), and fewer than expected shops selling that medication more often than outdated antimalarials when compared to random distribution (RR = 0.23, p = .007). All three of these clusters were co-located, overlapping in the northwest of the study area. CONCLUSION: Spatial clustering was found in the data. A concerning amount of correlation was found in one specific region in the study area where multiple behaviors converged in space, highlighting a prime target for interventions. These results also demonstrate the utility of applying geospatial methods in the study of medicine retailer behaviors, making the case for expanding this approach to other regions. PMID- 26896166 TI - Metagenomic analysis of rumen microbial population in dairy heifers fed a high grain diet supplemented with dicarboxylic acids or polyphenols. AB - BACKGROUND: The aim of this study was to investigate the effects of two feed supplements on rumen bacterial communities of heifers fed a high grain diet. Six Holstein-Friesian heifers received one of the following dietary treatments according to a Latin square design: no supplement (control, C), 60 g/day of fumarate-malate (organic acid, O) and 100 g/day of polyphenol-essential oil (P). Rumen fluid was analyzed to assess the microbial population using Illumina sequencing and quantitative real time PCR. RESULTS: The P treatment had the highest number of observed species (P < 0.10), Chao1 index (P < 0.05), abundance based coverage estimated (ACE) (P < 0.05), and Fisher's alpha diversity (P < 0.10). The O treatment had intermediate values between C and P treatments with the exception of the Chao1 index. The PCoA with unweighted Unifrac distance showed a separation among dietary treatments (P = 0.09), above all between the C and P (P = 0.05). The O and P treatments showed a significant increase of the family Christenenellaceae and a decline of Prevotella brevis compared to C. Additionally, the P treatment enhanced the abundance of many taxa belonging to Bacteroidetes, Firmicutes and Tenericutes phyla due to a potential antimicrobial activity of flavonoids that increased competition among bacteria. CONCLUSIONS: Organic acid and polyphenols significantly modified rumen bacterial populations during high-grain feeding in dairy heifers. In particular the polyphenol treatment increased the richness and diversity of rumen microbiota, which are usually high in conditions of physiological rumen pH and rumen function. PMID- 26896167 TI - Clinical characteristics of alcohol combined with other substance use disorders in an American Indian community sample. AB - BACKGROUND: Alcohol and other substance use disorders (SUD) pose major problems of morbidity and mortality in some American Indian communities, but little is known about the clinical characteristics, risk factors, and consequences of combined alcohol and other substance use disorders (multi-substance use disorder, MSUD) in those communities. METHODS: Using the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA), in a community sample of 876 American Indians, the clinical characteristics of lifetime DSM-5 moderate or severe alcohol use disorder alone (AUD alone) (n=146) and MSUD (defined as alcohol and >=1 other SUD) (n=284) were evaluated and compared to 347 participants with no lifetime SUD (no SUD). RESULTS: The majority (57%) of participants with a SUD had multi substance use disorder and 94% of those were with AUD. Stimulants (cocaine and/or amphetamine) and/or cannabis were the most common other SUDs. Participants with AUD alone were more likely to be male and have an earlier age of first alcohol intoxication than those with no SUD. Those with MSUD were more likely to have dropped out of high school, have antisocial personality disorder (ASPD) or conduct disorder (CD), have earlier ages of first alcohol intoxication and first use of cannabis and stimulants, an earlier age of onset of AUD, and more of several AUD symptoms than those with AUD alone, but the same temporal course and time to remission of AUD. CONCLUSIONS: MSUD is prevalent in this sample, is associated with multiple comorbidities and denotes a more severe alcohol syndrome than AUD alone. PMID- 26896168 TI - Assessing geographical differences in illicit drug consumption--A comparison of results from epidemiological and wastewater data in Germany and Switzerland. AB - BACKGROUND: Wastewater analysis is an innovative approach that allows monitoring illicit drug use at the community level. This study focused on investigating geographical differences in drug consumption by comparing epidemiological, crime and wastewater data. METHODS: Wastewater samples were collected in 19 cities across Germany and Switzerland during one week, covering a population of approximately 8.1 million people. Self-report data and consumption offences for the investigated areas were used for comparison and to investigate differences between the indicators. RESULTS: Good agreement between data sources was observed for cannabis and amphetamine-type stimulants, whereas substantial discrepancies were observed for cocaine. In Germany, an important distinction could be made between Berlin, Dortmund and Munich, where cocaine and particularly amphetamine were more prevalent, and Dresden, where methamphetamine consumption was clearly predominant. Cocaine consumption was relatively homogenous in the larger urban areas of Switzerland, although prevalence and offences data suggested a more heterogeneous picture. Conversely, marked regional differences in amphetamine and methamphetamine consumption could be highlighted. CONCLUSIONS: Combining the available data allowed for a better understanding of the geographical differences regarding prevalence, typology and amounts of substances consumed. For cannabis and amphetamine-type stimulants, the complementarity of survey, police and wastewater data could be highlighted, although notable differences could be identified when considering more stigmatised drugs (i.e. cocaine and heroin). Understanding illicit drug consumption at the national scale remains a difficult task, yet this research illustrates the added value of combining complementary data sources to obtain a more comprehensive and accurate picture of the situation. PMID- 26896170 TI - Bismuth(III) deferiprone effectively inhibits growth of Desulfovibrio desulfuricans ATCC 27774. AB - Sulfate-reducing bacteria have been implicated in inflammatory bowel diseases and ulcerative colitis in humans and there is an interest in inhibiting the growth of these sulfide-producing bacteria. This research explores the use of several chelators of bismuth to determine the most effective chelator to inhibit the growth of sulfate-reducing bacteria. For our studies, Desulfovibrio desulfuricans ATCC 27774 was grown with nitrate as the electron acceptor and chelated bismuth compounds were added to test for inhibition of growth. Varying levels of inhibition were attributed to bismuth chelated with subsalicylate or citrate but the most effective inhibition of growth by D. desulfuricans was with bismuth chelated by deferiprone, 3-hydroxy-1,2-dimethyl-4(1H)-pyridone. Growth of D. desulfuricans was inhibited by 10 MUM bismuth as deferiprone:bismuth with either nitrate or sulfate respiration. Our studies indicate deferiprone:bismuth has bacteriostatic activity on D. desulfuricans because the inhibition can be reversed following exposure to 1 mM bismuth for 1 h at 32 degrees C. We suggest that deferiprone is an appropriate chelator for bismuth to control growth of sulfate-reducing bacteria because deferiprone is relatively nontoxic to animals, including humans, and has been used for many years to bind Fe(III) in the treatment of beta-thalassemia. PMID- 26896169 TI - Impact of alcohol use on sexual behavior among men who have sex with men and transgender women in Lima, Peru. AB - BACKGROUND: Alcohol use disorders (AUDs) may enhance the likelihood of risky sexual behaviors and the acquisition of sexually transmitted infections (STIs). Associations between AUDs with condomless anal intercourse (CAI) and STI/HIV prevalence were assessed among men who have sex with men (MSM) and transgender women (TW) in Lima, Peru. METHODS: MSM and TW were eligible to participate based on a set of inclusion criteria which characterized them as high-risk. Participants completed a bio-behavioral survey. An AUDIT score >=8 determined AUD presence. Recent STI diagnosis included rectal gonorrhea/chlamydia, syphilis, and/or new HIV infection within 6 months. Prevalence ratios (PR) were calculated using Poisson regression. RESULTS: Among 312 MSM and 89 TW, 45% (181/401) had an AUD. Among those with an AUD, 164 (91%) were hazardous/harmful drinkers, and 17 (9%) had alcohol dependence. Higher CAI was reported by participants with an AUD vs. without, (82% vs. 72% albeit not significant). Reporting anal sex in two or more risky venues was associated with screening AUD positive vs. not (24% vs. 15%, p=0.001). There was no difference in recent STI/HIV prevalence by AUD status (32% overall). In multivariable analysis, screening AUD positive was not associated with CAI or recent STI/HIV infection. CONCLUSIONS: In our sample AUDs were not associated with CAI or new HIV infection/recent STI. However higher prevalence of CAI, alcohol use at last sex, and anal sex in risky venues among those with AUDs suggests that interventions to reduce the harms of alcohol should be aimed toward specific contexts. PMID- 26896173 TI - Shaving a Shell: Effect of Manipulated Sculpture and Feeding on Shell Growth and Sculpture Development in Nucella lamellosa (Muricidae: Ocenebrinae). AB - Gastropod shell sculpture offers a novel tool for studying morphological patterning. Existing shell features may be manipulated experimentally to test how alteration affects subsequent shell growth and form. Axial sculpture occurs in many gastropod groups, and spacing of sculpture may be regular or irregular. But how gastropods control sculpture placement during shell growth is unknown. We studied the growth and positioning of axial lamellae in the muricid Nucella lamellosa, and compared these to the superficially similar axial varices seen in other muricids. First, we tested whether the feeding rate had any effect on the rate of addition or positioning of new lamellae. Second, we tested what effect previous shell sculpture had on lamellar placement, and shell growth in general, by removing all shell sculpture and allowing snails to grow over the "shaved" shell surface. Lamellar growth appeared to be relatively plastic; spacing was highly variable both within and among individual snails, and 1-2 weeks were required to complete the addition of a new lamella. Body growth rate was the primary determinant of lamellar growth; past lamellae had no effect on placement of new lamellae or rate of shell length increase. Feeding rate and body size affected only growth in shell length, and had no direct effect on spacing or on the rate of addition of new lamellae. The growth of axial lamellae in N. lamellosa differed from that of varices by exhibiting neither a) regular spacing nor b) a growth hiatus after completion of a lamella. Significantly, despite the obvious impediment of previous sculpture to future shell growth, removal of this sculpture had no observable effect on the rate of body growth or on any aspect of subsequent lamellar growth. PMID- 26896172 TI - Relationships between adult asthma and oxidative stress markers and pH in exhaled breath condensate: a systematic review. AB - Oxidative stress has a recognized role in the pathophysiology of asthma. Recently, interest has increased in the assessment of pH and airway oxidative stress markers. Collection of exhaled breath condensate (EBC) and quantification of biomarkers in breath samples can potentially indicate lung disease activity and help in the study of airway inflammation, and asthma severity. Levels of oxidative stress markers in the EBC have been systematically evaluated in children with asthma; however, there is no such systematic review conducted for adult asthma. A systematic review of oxidative stress markers measured in EBC of adult asthma was conducted, and studies were identified by searching MEDLINE and SCOPUS databases. Sixteen papers met the inclusion criteria. Concentrations of exhaled hydrogen ions, nitric oxide products, hydrogen peroxide and 8 isoprostanes were generally elevated and related to lower lung function tests in adults with asthma compared to healthy subjects. Assessment of EBC markers may be a noninvasive approach to evaluate airway inflammation, exacerbations, and disease severity of asthma, and to monitor the effectiveness of anti-inflammatory treatment regimens. Longitudinal studies, using standardized analytical techniques for EBC collection, are required to establish reference values for the interpretation of EBC markers in the context of asthma. PMID- 26896171 TI - Inhibition of Soluble Tumor Necrosis Factor Prevents Chemically Induced Carcinogenesis in Mice. AB - TNF is a potent promoter of carcinogenesis and potentially important target for cancer prevention. TNF is produced as functionally distinct transmembrane and soluble molecules (tmTNF and sTNF, respectively), but their individual roles in carcinogenesis are unexplored. We investigated the participation of tmTNF and sTNF in chemically induced carcinogenesis in mice. We found that injection of XPro1595, a dominant-negative TNF biologic (DN-TNF) and specific antagonist of sTNF, decreased tumor incidence and growth, and prolonged survival of 3 methylcholanthrene (MCA)-injected mice. Similar results were obtained following the exclusion of both TNF forms by either TNF-receptor 2-Fc fusion protein (TNFR2 Fc) treatment or TNF gene deletion. In addition, gene deletion of TNFR1, which is preferentially triggered by sTNF, was temporarily blocked, whereas gene deletion of TNFR2, which is preferentially triggered by tmTNF, enhanced MCA-induced carcinogenesis. Concomitantly with carcinogenesis induction, MCA increased circulating IL1alpha, accumulation of myeloid-derived suppressor cells (MDSC), STAT3 phosphorylation, and immunosuppression in the spleen. In sharp contrast, DN TNF treatment dramatically decreased IL1alpha and increased the essential immunoregulatory cytokines IL1beta, IL12p70, and IL17 in the peripheral blood of MCA-injected mice. In addition, MDSC accumulation, STAT3 phosphorylation, and immunosuppression in MCA-injected mice were prevented by DN-TNF treatment, TNFR2 Fc treatment, and/or gene deletion of TNF or TNFR1, but not deletion of TNFR2. These findings reveal that sTNF is both an essential promoter of carcinogenesis and a pivotal regulator of MDSCs, and indicate that sTNF could be a significant target for cancer prevention and therapy. Cancer Immunol Res; 4(5); 441-51. (c)2016 AACR. PMID- 26896174 TI - Entrainment of the Circadian Rhythm in Egg Hatching of the Crab Dyspanopeus sayi by Chemical Cues from Ovigerous Females. AB - The subtidal crab Dyspanopeus sayi has a circadian rhythm in larval release with a free-running period of 24.1 h. Under constant conditions, eggs hatch primarily in the 4-h interval after the time of sunset. The study tested the new model for entrainment in subtidal crabs, which proposes that the female perceives the environmental cycles and entrains the endogenous rhythm in the embryos. Results verified the model for D. sayi. Hatching by embryos collected from the field when they had not yet developed eye pigments, and were kept in constant conditions attached to their mother, exhibited the circadian hatching rhythm. Attached embryos could also be entrained to a new photoperiod in the laboratory before they developed eye pigments. Further, mature embryos removed from the female hatched rhythmically, indicating that a circadian rhythm resides in the embryos. However, if mature embryos with eye pigments were removed from the female and exposed to a new light-dark cycle, they could not be entrained to the new cycle; rather, they hatched according to the timing of the original light-dark cycle. Nevertheless, detached, mature embryos would entrain to a new light-dark cycle if they were in chemical, but not physical, contact with the female. Thus, the female perceives the light-dark cycle, and uses chemical cues to entrain the circadian rhythm of hatching by the embryos. PMID- 26896175 TI - Development of the Sea Star Echinaster (Othilia) brasiliensis, with Inference on the Evolution of Development and Skeletal Plates in Asteroidea. AB - We describe the development and juvenile morphology of the sea star Echinaster (Othilia) brasiliensis in order to explore evolutionary developmental modes and skeletal homologies. This species produces large, buoyant eggs (0.6 +/- 0.03 mm diameter), and has a typical lecithotrophic brachiolaria larva. The planktonic brachiolaria larva is formed 2-4 days after fertilization, when cilia cover the surface. Early juveniles are completely formed by 18 days of age. Initial growth is supported by maternal nutrients while the stomach continues to develop until 60 days after fertilization, when juveniles reach about 0.5 mm of radius length. The madreporite was observed 88 days after fertilization. In the youngest juvenile skeleton of E. (O.) brasiliensis, the madreporite and odontophore are homologous to those of other recent, non-paxillosid asteroids, and follow the Late Madreporic Mode. The emergence of plates related to the ambulacral system follows the Ocular Plate Rule. The development and juvenile skeletal morphology of this species are similar to those of the few other studied species in the genus Echinaster. This study corroborates the notion that the mode of development -including a short-lived lecithotrophic brachiolaria larva--in all Echinaster species shares a similar pattern that may be conserved throughout the evolutionary history of the group. PMID- 26896176 TI - Behavioral Thermoregulation and Trade-Offs in Juvenile Lobster Homarus americanus. AB - Water temperature influences the behavior and distribution patterns of both larval and adult American lobster Homarus americanus. However, very little is known about the responses of juvenile lobsters. The juvenile life stage is a critical period; high levels of mortality, combined with specific behavioral responses, can disconnect larval settlement from patterns of abundance of adults. We assessed behavioral thermoregulation in juvenile lobsters, and determined how thermal preferences can be altered by the presence of shelter and food. Juvenile lobsters avoided temperatures higher than 20 degrees C and lower than 8 degrees C, and had a mean temperature preference of 16.2 +/- 1 degrees C. This preference was unaffected by prior acclimation, origin (laboratory-raised or wild), or size. When the animals were subjected to a temperature change (5-20 degrees C), activity rates peaked at 15 degrees C, and remained stable thereafter. Activity rates did not change when a shelter was added. The addition of food resulted in an increase in activity associated with food handling. When juvenile lobsters were offered a choice between temperature, shelter, and food, they always chose the environment with a shelter, even when it was in a thermally unfavorable temperature. Juveniles also spent more time in a thermally unfavorable environment when food was present; however, acquisition of a shelter was prioritized over food. Although juveniles had a similar thermal preference to adults, they are more vulnerable to predation; the innate shelter-seeking behavior of juveniles overrode their thermal preference. While temperature is an important environmental factor affecting the physiology, distribution, and growth of aquatic ectotherms, our findings suggest that trade-off behaviors occur in order to maintain optimal fitness and survival of the individual. PMID- 26896177 TI - Plastic Sexual Expression in the Androdioecious Barnacle Octolasmis warwickii (Cirripedia: Pedunculata). AB - Most barnacles are simultaneous hermaphrodites, but dwarf males are also found attached to hermaphrodites in several species. This biologically rare phenomenon of the coexistence of males and hermaphrodites is termed androdioecy. To test whether the hermaphrodite and male sexes are fixed or plastic in the androdioecious pedunculate barnacle Octolasmis warwickii, we conducted a series of 22-day-long transplanting experiments to evaluate the effects of a) the original site (attached to the conspecific vs. attached directly to the substrate) and b) the transplanting site (conspecific-attached vs. substrate attached). Penis length (as an index of male function), the presence or absence of egg mass (female function), and growth rate were investigated. As with natural dwarf males, individuals that were transplanted onto conspecifics developed longer penises than did those that were transplanted onto the substrate. The original site of attachment also affected penis length. However, no significant effects of the original site or the transplanting were detected in egg-laying activities, as only one experimental individual laid eggs. Individuals that were transplanted onto conspecifics grew less than those that were attached to the substrate. These results indicate that individual sexual expression is affected by the environment in O. warwickii. PMID- 26896178 TI - Two Activin Type 2B Receptors from Sea Bream Function Similarly in vitro. AB - Myostatin (MSTN) and activin are members of the transforming growth factor-beta superfamily. Both signal through the activin type II receptors (ActRII and ActRIIB). In a previous report, we demonstrated that fish possess at least 2 genes for ActRIIB: ActRIIB-1 and ActRIIB-2, which differ in their amino acid sequence. We also showed that affinity-purified, fish-soluble ActRIIB-1 (extracellular domain; ECD), produced in the yeast Pichia pastoris, inhibited recombinant mouse/rat/human mature MSTN activity in vitro using a reporter gene assay in the mammalian A204 cell line. In the present study, we produced soluble ActRIIB-2a in P. pastoris, and showed that it is N-glycosylated, similar to soluble ActRIIB-1. Inhibition of MSTN and activin A activities by affinity purified ActRIIB-2a was compared with that of soluble ActRIIB-1 using the CAGA luciferase assay in A204 cells. The findings of this study provide evidence that both paralogs, which probably resulted from gene duplication, did not diversify in their functionality (neofunctionalization), but rather retained a similar function. Both ActRIIB isoforms are equally potent in the mammalian system, and both exhibited an inhibitory effect on mammalian MSTN and activin A. Moreover--in spite of the amino acid differences in ECD between the two paralogs--it appears that the residues important for ligand binding are conserved, and that they recognize the mammalian ligands activin A and MSTN to the same extent. PMID- 26896179 TI - Octocoral Sarcophyton auritum Verseveldt & Benayahu, 1978: Microanatomy and Presence of Collagen Fibers. AB - The study presents the microanatomy of the polyps of the reef-dwelling octocoral Sarcophyton auritum. We demonstrate the presence of its unique collagen fibers in the colony by means of Masson Trichrome histological staining. Based on peptide profiling, mass spectroscopy analysis confirmed that the fiber proteins were homologous with those of mammalian collagen. Histological and electron microscopy results showed that six of the eight mesenterial filaments of the polyps possess an internal, coiled, spring-like collagen fiber. High-resolution electron microscopy revealed for the first time in cnidarian collagen the interwoven, three-dimensional arrangement of the fibrils that comprise the fibers. Some fibrils feature free ends, while others are bifurcated, the latter being attributed to collagen undergoing fibrogenesis. Along with the mass spectroscopy finding, the coiled nature of the fibers and the fibril microanatomy show a resemblance to those of vertebrates, demonstrating the conserved nature of collagen fibers at both the biochemical and ultrastructural levels. The location, arrangement, and small diameter of the fibers and fibrils of S. auritum may provide a highly protective factor against occasional rupture and injury during the bending of the octocoral's extended polyps under strong current conditions; that is, providing the octocoral with a hydromechanical support. The findings from the microanatomical features of these unique fibers in S. auritum, as well as their suggested function, raise the potential for translation to biomedical applications. PMID- 26896180 TI - Intraspecific Scaling Relationships Between Crawling Speed and Body Size in a Gastropod. AB - Across various modes of locomotion, body size and speed are often correlated both between and within species. Among the gastropods, however, current data are minimal for interspecific and intraspecific scaling relationships. In this study, we tested the relationships between various measurements of body size and crawling speed in the terrestrial snail Cornu aspersum. We also investigated the relationships between crawling speed, muscular wave frequency, and muscular wavelength, because--while these relationships within individuals are well studied--the relationships among individuals are unknown. We recorded snails crawling on both a horizontal and a vertical surface. We found that when they crawled on a horizontal surface, foot length was positively correlated with pedal wavelength and crawling speed, but was not correlated with wave frequency. In comparison, when they crawled on a vertical surface, foot length was positively correlated with wavelength, negatively correlated with wave frequency, and not correlated with crawling speed. Body mass had no correlation with crawling speed when snails were crawling on a horizontal surface, but was negatively correlated with speed when snails crawled on a vertical surface. PMID- 26896181 TI - Cutaneous Strongyloides Infection Postchemotherapy. AB - BACKGROUND AND OBJECTIVE: While clinical symptoms of strongyloidiasis are often nonspecific, larva currens (with erythematous, serpiginous, and pruritic papules and plaques) should prompt investigation including stool microscopy, serology, and skin biopsy of the lesion. Appropriate diagnosis and treatment with ivermectin is necessary, especially in the immunocompromised patient who is at increased risk for hyperinfection syndrome and disseminated disease. CONCLUSION: We present a 61-year-old immunocompromised man with presentation of larva currens of cutaneous strongyloides infection without symptoms of hyperinfection or disseminated disease. PMID- 26896182 TI - Regional forecast model for the Olea pollen season in Extremadura (SW Spain). AB - The olive tree (Olea europaea) is a predominantly Mediterranean anemophilous species. The pollen allergens from this tree are an important cause of allergic problems. Olea pollen may be relevant in relation to climate change, due to the fact that its flowering phenology is related to meteorological parameters. This study aims to investigate airborne Olea pollen data from a city on the SW Iberian Peninsula, to analyse the trends in these data and their relationships with meteorological parameters using time series analysis. Aerobiological sampling was conducted from 1994 to 2013 in Badajoz (SW Spain) using a 7-day Hirst-type volumetric sampler. The main Olea pollen season lasted an average of 34 days, from May 4th to June 7th. The model proposed to forecast airborne pollen concentrations, described by one equation. This expression is composed of two terms: the first term represents the resilience of the pollen concentration trend in the air according to the average concentration of the previous 10 days; the second term was obtained from considering the actual pollen concentration value, which is calculated based on the most representative meteorological variables multiplied by a fitting coefficient. Due to the allergenic characteristics of this pollen type, it should be necessary to forecast its short-term prevalence using a long record of data in a city with a Mediterranean climate. The model obtained provides a suitable level of confidence to forecast Olea airborne pollen concentration. PMID- 26896183 TI - Longitudinal analysis of the neurological features of ataxia-telangiectasia. AB - AIM: To assess the relationship between genotype and neurological progression in ataxia-telangiectasia (A-T). METHODS: Clinical and laboratory data were extracted retrospectively from the records of patients attending the UK National Ataxia Telangiectasia Clinic. Neurological assessments were performed using the A-T Index (Crawford Score) and the A-T Neurological Examination Scale Toolkit (A-T NEST). Variables influencing phenotype were identified by using an information theoretic approach starting from a maximal model to generate estimates of coefficients for each variable. Per-individual progression was assessed for patients with three or more clinic attendances. RESULTS: The genotype could be determined for 125/135 patients. Crawford and A-T NEST scores were well correlated. For both scoring systems the estimated coefficients were significantly positive for Age x kinase activity but not Age x protein expression. Unlike the per-genotype analysis, the individual progression of neurological scores in the 34 patients that attended on three or more occasions was not smooth and linear (and in some cases improved over time). INTERPRETATION: Residual kinase activity confers a milder phenotype but there is no difference between kinase-dead and protein-null genotypes. The non-linear progression of individual patients' neurological scores may reflect biological complexity, day to-day variability, limitations of the assessment methods or a combination of all three. PMID- 26896184 TI - Identifying new Risk Markers and Potential Targets for Coronary Artery Disease: The Value of the Lipidome and Metabolome. AB - PURPOSE: This systematic review was performed to summarize published data on lipidomic and metabolomic risk markers of coronary artery disease. METHODS: Studies were identified from a literature search of PubMed. RESULTS: Published data shows that analysis of metabolites and lipids offers an opportunity to increase our knowledge of the biological processes related to development and progression of atherosclerotic coronary disease. It is evident that advanced analytical technologies are able to detect and identify a large number of molecules that may have important structural and functional roles over and above currently used biomarkers in the cardiovascular field. It is suggested in a number of reports that the novel biomarkers can be used to improve risk stratification and patient selection for different treatments. Also, monitoring treatment efficacy and safety as well as lifestyle changes should be facilitated by such novel markers. CONCLUSION: Until now a plethora of biomarker candidates associated with cardiovascular event risk have been identified, but very few have passed through clinical and analytical validation and found their way into clinical use. Consequently, the appetite of physicians to use these novel tests in daily clinical routine has not yet been truly tested. PMID- 26896186 TI - Effective enzymatic caffeoylation of natural glucopyranosides. AB - Reaction system was developed for enzymatic caffeoylation of model saccharidic acceptor methyl beta-d-glucopyranoside to obtain exclusively methyl 6-O-caffeoyl beta-D-glucopyranoside. Reaction with starting concentration of acceptor 0.2 M provided 73% yield of purified product within 17 days. Reactions with low acceptor concentrations (0.04 and 0.08 M) run to the completion within 7 days. Such highly effective and regioselective reaction was promoted by Lipozyme TL IM in tert-butanol, using vinyl caffeate as acylation donor. The optimized reaction conditions were used in preparative caffeoylation of natural substances-arbutin and salidroside, giving 75% of 6-O-caffeoylated arbutin (robustaside B) and 74% of 6-O-caffeoylated salidroside as the only products after 12 and 16 days, respectively. PMID- 26896185 TI - Human Genetics and the Causal Role of Lipoprotein(a) for Various Diseases. AB - Lipoprotein(a) [Lp(a)] is a highly atherogenic lipoprotein that is under strong genetic control by the LPA gene locus. Genetic variants including a highly polymorphic copy number variation of the so called kringle IV repeats at this locus have a pronounced influence on Lp(a) concentrations. High concentrations of Lp(a) as well as genetic variants which are associated with high Lp(a) concentrations are both associated with cardiovascular disease which very strongly supports causality between Lp(a) concetrations and cardiovascular disease. This method of using a genetic variant that has a pronounced influence on a biomarker to support causality with an outcome is called Mendelian randomization approach and was applied for the first time two decades ago with data from Lp(a) and cardiovascular disease. This approach was also used to demonstrate a causal association between high Lp(a) concentrations and aortic valve stenosis, between low concentrations and type-2 diabetes mellitus and to exclude a causal association between Lp(a) concentrations and venous thrombosis. Considering the high frequency of these genetic variants in the population makes Lp(a) the strongest genetic risk factor for cardiovascular disease identified so far. Promising drugs that lower Lp(a) are on the horizon but their efficacy in terms of reducing clinical outcomes still has to be shown. PMID- 26896189 TI - Potential effects of pleasant and cold stimuli on nausea and vomiting induced by disgusting tastes. AB - Several pharmacological agents have disgusting tastes that are perceived strongly in the back of the mouth and may trigger nausea and vomiting (NV), resulting in poor adherence to medication schedules and negative impacts on clinical outcomes. Pleasant stimuli and cold temperature lessen the disgusting stimuli, lowering NV through different mechanisms. A pleasant stimulus can mask an unpleasant one, presumably through lateral inhibitory connections in the local neuronal circuit. Similarly, temperature deeply influences taste perception because the response to bitter as well as to salty and sour has been found to assume a reversed U-shaped form, being reduced by cooling to 18 degrees C and enhanced by warming to 30-37 degrees C. This Review describes the mechanisms by which pleasant and cold stimuli may mask emetogenic disgusting stimuli and identifies the potential clinical applications of cooling for inhibiting objectionable drug-related gustatory reactions. (c) 2015 Wiley Periodicals, Inc. PMID- 26896187 TI - The high frequency of GJB2 gene mutation c.313_326del14 suggests its possible origin in ancestors of Lithuanian population. AB - BACKGROUND: Congenital hearing loss (CHL) is diagnosed in 1 - 2 newborns in 1000, genetic factors contribute to two thirds of CHL cases in industrialised countries. Mutations of the GJB2 gene located in the DFNB1 locus (13q11-12) are a major cause of CHL worldwide. The aim of this cross-sectional study was to assess the contribution of the DFNB1 locus containing the GJB2 and GJB6 genes in the development of early onset hearing loss in the affected group of participants, to determine the population-specific mutational profile and DFNB1-related HL burden in Lithuanian population. METHODS: Clinical data were obtained from a collection of 158 affected participants (146 unrelated probands) with early onset non syndromic HL. GJB2 and GJB6 gene sequencing and GJB6 gene deletion testing were performed. The data of GJB2 and GJB6 gene sequencing in 98 participants in group of self-reported healthy Lithuanian inhabitants were analysed. Statistic summary, homogeneity tests, and logistic regression analysis were used for the assessment of genotype-phenotype correlation. RESULTS: Our findings show 57.5% of affected participants with two pathogenic GJB2 gene mutations identified. The most prevalent GJB2 mutations were c.35delG, p. (Gly12Valfs*2) (rs80338939) and c.313_326del14, p. (Lys105Glyfs*5) (rs111033253) with allele frequencies 64.7% and 28.3% respectively. GJB6 gene mutations were not identified in the affected group of participants. The statistical analysis revealed significant differences between GJB2(-) and GJB2(+) groups in disease severity (p = 0.001), and family history (p = 0.01). The probability of identification of GJB2 mutations in patients with various HL characteristics was estimated. The carrier rate of GJB2 gene mutations - 7.1% (~1 in 14) was identified in the group of healthy participants and a high frequency of GJB2-related hearing loss was estimated in our population. DISCUSSION: The results show a very high proportion of GJB2 positive individuals in the research group affected with sensorineural HL. The allele frequency of c.35delG mutation (64.7 %) is consistent with many previously published studies in groups of affected individuals of Caucasian populations. The high frequency of the c.313_326del14 (28.3 % of pathogenic alleles) mutation in affected group of participants was an unexpected finding in our study suggesting not only a high frequency of carriers of this mutation in our population but also its possible origin in Lithuanian ancestors. The high frequency of carriers of the c.313_326del14 mutation in the entire Lithuanian population is supported by it being identified twice in the ethnic Lithuanian group of healthy participants (a frequency 2.0 % of carriers in the study group). CONCLUSION: Analysis of the allele frequency of GJB2 gene mutations revealed a high proportion of c. 313_326del14 (rs111033253) mutations in the GJB2-positive group suggesting its possible origin in Lithuanian forebears. The high frequency of carriers of GJB2 gene mutations in the group of healthy participants corresponds to the substantial frequency of GJB2-associated HL in Lithuania. The observations of the study indicate the significant contribution of GJB2 gene mutations to the pathogenesis of the disorder in the Lithuanian population and will contribute to introducing principles to predict the characteristics of the disease in patients. PMID- 26896190 TI - Answer to the letter of John E. Madias. PMID- 26896192 TI - Outcome of renal proximal tubular dysfunction with Fanconi syndrome caused by sodium valproate. AB - BACKGROUND: Although Fanconi syndrome is rare in patients with epilepsy treated with sodium valproate (VPA), the prevalence might be higher in children with severe motor and intellectual disabilities (SMID). VPA-induced Fanconi syndrome usually has a favorable outcome, but the long-term outcome of renal tubular dysfunction in SMID patients remains unknown. The aim of this study was therefore to investigate the long-term outcome of renal proximal dysfunction in SMID children with Fanconi syndrome caused by VPA. METHODS: The records of six children with SMID and Fanconi syndrome caused by VPA were retrospectively reviewed to assess long-term proximal renal tubular function after discontinuation of VPA. All six patients had intractable epilepsy and required tube feeding. RESULTS: Proximal tubular dysfunction improved in almost all patients after VPA discontinuation, although abnormal uric acid reabsorption persisted in three patients. Five patients had hypocarnitinemia. After carnitine supplementation, one of these three patients with decreased ability to reabsorb uric acid had a normal serum level and improved fractional excretion of uric acid. CONCLUSIONS: Secondary carnitine deficiency may cause prolonged tubular dysfunction in some SMID patients with VPA-induced Fanconi syndrome. Fanconi syndrome caused by VPA is a usually reversible dysfunction of the proximal tubules, but can be permanent. Although not effective for all patients, carnitine is recommended for patients with VPA-induced Fanconi syndrome, especially children with SMID. PMID- 26896193 TI - Higher burnout scores in paediatric residents are associated with increased brain activity during attentional functional magnetic resonance imaging task. AB - AIM: Burnout syndrome is common in healthcare workers. We evaluated its prevalence in paediatric residents and investigated its influence on cerebral function correlations, using functional magnetic resonance imaging (MRI), when they carried out an attentional paradigm. METHODS: This cross-sectional descriptive study involved 28 residents from the Department of Paediatrics at the University of Sao Paulo. The functional MRI was carried out while the residents completed the Stroop colour word task paradigm to investigate their attentional task performance. The Maslach Burnout Inventory (MBI) was applied, and stress was assessed using the Lipp Inventory of Stress Symptoms for Adults and by a visual analogue mood scale. RESULTS: The MBI subscales of depersonalisation and emotional exhaustion indicated that 53.1% of the residents had moderate or high burnout syndrome. The whole-brain multivariate analysis showed positive correlations between the blood oxygenation level dependent effect and the MBI depersonalisation and emotional exhaustion indices in the dorsolateral prefrontal cortex, which controls for anxiety. CONCLUSION: Increased brain activation during an attention task, measured using functional MRI, was associated with higher burnout scores in paediatric residents. This study provides a biological basis for the implementation of measures to reduce burnout syndrome at the start of residency training programmes. PMID- 26896194 TI - Donor-Specific HLA Antibodies in Living Versus Deceased Donor Liver Transplant Recipients. AB - With less ischemia, improved donor selection and controlled procedures, living donor liver transplantation (LDLT) might lead to less HLA donor-specific antibody (DSA) formation or fewer adverse outcomes than deceased donor liver transplantation (DDLT). Using the multicenter A2ALL (Adult-to-Adult Living Donor Liver Transplantation Cohort Study) biorepository, we compared the incidence and outcomes of preformed and de novo DSAs between LDLT and DDLT. In total, 129 LDLT and 66 DDLT recipients were identified as having serial samples. The prevalence of preformed and de novo DSAs was not different between DDLT and LDLT recipients (p = 0.93). There was no association between patient survival and the timing (preformed vs. de novo), class (I vs. II) and relative levels of DSA between the groups; however, preformed DSA was associated with higher graft failure only in DDLT recipients (p = 0.01). De novo DSA was associated with graft failure regardless of liver transplant type (p = 0.005) but with rejection only in DDLT (p = 0.0001). On multivariate analysis, DSA was an independent risk factor for graft failure regardless of liver transplant type (p = 0.017, preformed; p = 0.002, de novo). In conclusion, although similar in prevalence, DSA may have more impact in DDLT than LDLT recipients. Although our findings need further validation, future research should more robustly test the effect of donor type and strategies to mitigate the impact of DSA. PMID- 26896195 TI - [A new classification for meibomian gland diseases with in vivo confocal microscopy]. AB - INTRODUCTION: Meibomian gland dysfunction (MGD) is a frequent disorder often associated with dry eye disease. Slit-lamp examination with digital expression of the tarsal Meibomian glands allows examination of the contents of the distal Meibomian gland and the meatus. However, the Meibomian epithelium, interglandular space and proximal secretions cannot be clinically assessed. In vivo confocal microscopy (IVCM) is a rapid and non-invasive imaging technique that provides high-resolution images of the ocular surface and eyelids. The primary objective of the present study was to establish a classification of MGD with IVCM. Secondary objectives were to evaluate this scoring system by analyzing the correlation with OSDI, infrared (IR) meibography and Demodex infestation. MATERIAL AND METHODS: Forty-six dry eye patients (Ocular Surface Disease Index [OSDI] >13) associated with MGD were enrolled. Ten healthy subjects without dry eye disease or blepharitis were also included as controls. An OSDI questionnaire, clinical examination, IVCM and infrared meibography of the lower lid were performed in all subjects by the same examiner. RESULTS: A new MGD score was established based on IVCM findings: the first stage was Meibomian obstruction with a clear epithelium, the second stage was an inflammatory state with Meibomian gland obstruction, epithelial and interglandular inflammation, and the last stage was glandular fibrosis. This score was significantly correlated with the meiboscore obtained with infrared meibography (correlation coefficient 0.47, CI95% [0.22-0.66]). CONCLUSION: IVCM of the Meibomian gland complex complements the clinical examination by determining the stage of dysfunction and may help clinicians evaluate and treat MGD. PMID- 26896196 TI - The Future of Pediatric Obesity. AB - The National Health and Nutrition Examination Survey from the Centers for Disease Control and Prevention reports a steady increase in obesity over the last 30 years. The greatest increase was seen in 15 to 19 year olds, whose obesity prevalence almost doubled from 10.5% to 19.4%. The solution to pediatric obesity requires a multidisciplinary approach addressing cultural norms, technologic advances, and family engagement. Future treatment strategies to combat the obesity epidemic will have to extend beyond the health care provider's office. Behavior modification remains the key component to pediatric obesity prevention and treatment. PMID- 26896197 TI - Health Care Systems and National Policy: Role of Leadership in the Obesity Crisis. AB - Obesity, defined as a body mass index (BMI) of 30 or higher in adults and BMI in the 95th percentile or higher for children, is epidemic in the United States. The predominant culture of caloric excess and sedentary behaviors contributes to this problem. Obesity increases the risk of many chronic diseases and premature death. The broad response to this costly disease includes efforts from medical providers, local and federal governments, and nongovernmental agencies. Although obesity can be addressed on an individual basis, it is largely recognized as a public health issue. PMID- 26896199 TI - Multidisciplinary Teams and Obesity: Role of the Modern Patient-Centered Medical Home. AB - With the growing obesity epidemic, it is difficult for individual primary care providers to devote the time and effort necessary to achieve meaningful weight loss for significant numbers of patients. A variety of health care professionals provide value and evidence-based care that is effective in treating obesity and other preventable diseases. Multidisciplinary collaboration between primary care physicians and other trained health professionals within patient-centered medical homes offers an effective approach to sustainable behavioral treatment options for individuals who are obese or overweight. PMID- 26896198 TI - Obesity Prevention and Screening. AB - Obesity is widespread, associated with several physical and psychosocial comorbidities, and is difficult to treat. Prevention of obesity across the lifespan is critical to improving the health of individuals and society. Screening and prevention efforts in primary care are an important step in addressing the obesity epidemic. Each period of human development is associated with unique risks, challenges, and opportunities for prevention and intervention. Screening tools for overweight/obesity, although imperfect, are quick and easy to administer. Screening should be conducted at every primary care visit and tracked longitudinally. Screening tools and cutoffs for overweight and obesity vary by age group. PMID- 26896200 TI - Past, Present, and Future of Pharmacologic Therapy in Obesity. AB - Medications for obesity management can be divided into 4 groups: antidepressants (naltrexone/bupropion), stimulants (phentermine, phendimetrazine, diethylpropion, phentermine/topiramate), fat blockers (orlistat), and diabetes medications (liraglutide). Each group has specific therapeutic effects, adverse effects, and costs. Two medications are indicated for long-term use in obesity: lorcaserin and orlistat. Other available medications are for short-term use. High cost makes many of these medications inaccessible for underserved and poor patients. Because of misuse potential, many obesity medications are also classified as controlled substances. There are no medications currently approved for use in pregnant or lactating women. PMID- 26896201 TI - Nutritional Therapy. AB - This article provides the reader with steps needed to accurately assess patient nutrition behaviors that contribute to weight gain, inability to lose weight, or inability to sustain weight loss. Evidence-based approaches in nutrition therapy that can create the daily energy deficit needed to produce 1/2 to 2 pounds of weight loss per week, and the strategies to create the energy deficit, are presented. To optimize health, long-term weight loss maintenance is needed. The benefits of using a multidisciplinary team approach in treating obesity are highlighted. PMID- 26896202 TI - Economic Impact of Obesity. AB - Parallel to rising obesity rates is an increase in costs associated with excess weight. Estimates of future direct (medical) and indirect (nonmedical) costs related to obesity suggest rising expenditures that will impose a significant economic burden to individuals and society as a whole. This article reviews research on direct and indirect medical costs and future economic trends associated with obesity and associated comorbidities. Cost disparities associated with subsets of the population experiencing higher than average rates of obesity are explored. Finally, potential solutions with the highest estimated impact are offered, and future directions are proposed. PMID- 26896203 TI - Impacts of Physical Activity on the Obese. AB - Approximately two-thirds of the US population is overweight or obese. Physical activity is recommended for preventing obesity, aiding in weight loss, and decreasing rates of chronic diseases. This article reviews current statistics for obesity, physical activity, and physician counseling patterns. Principles of exercise physiology relating to cardiopulmonary fitness and chronic disease are also reviewed and methods for increasing physical activity in adults and children are suggested. PMID- 26896204 TI - Obesity in Special Populations: Pregnancy. AB - Perinatal overweight and obesity is a major public health and clinical care issue that requires deliberate and immediate attention. Preconception and prenatal assessment and counseling should address the risks associated with obesity, recommendations for weight gain, proper nutrition and dietary intake, and physical activity. Nutrition and exercise guidance should be offered to all perinatal overweight and obese women with an emphasis on effective strategies to overcome barriers. All women should be encouraged to adopt a healthy lifestyle and achieve a healthy weight before becoming pregnant. PMID- 26896206 TI - Obesity in Older Adults. AB - The percentage of older obese adults is on the rise. Many clinicians underestimate the health consequences of obesity in the elderly, citing scarce evidence and concerns that weight loss might be detrimental to the health of older adults. Although overweight and obese elders are not at the same risk for morbidity and mortality as younger individuals, quality of life and function are adversely impacted. Weight loss plans in the elderly should include aerobic activities as well as balance and resistance activities to maintain optimal physical function. PMID- 26896205 TI - Obesity Statistics. AB - Obesity is a chronic disease that is strongly associated with an increase in mortality and morbidity including, certain types of cancer, cardiovascular disease, disability, diabetes mellitus, hypertension, osteoarthritis, and stroke. In adults, overweight is defined as a body mass index (BMI) of 25 kg/m(2) to 29 kg/m(2) and obesity as a BMI of greater than 30 kg/m(2). If current trends continue, it is estimated that, by the year 2030, 38% of the world's adult population will be overweight and another 20% obese. Significant global health strategies must reduce the morbidity and mortality associated with the obesity epidemic. PMID- 26896207 TI - Surgical Management of Metabolic Syndrome Related to Morbid Obesity. AB - Current treatment approaches in morbid obesity are multimodal in nature. Combination therapies include increases in moderate-intensity aerobic and resistance exercise; behavioral lifestyle changes to increase compliance with diet and activity recommendations; medical nutrition therapy; intensive medical therapy; and metabolic surgical procedures, such as gastric bypass and vertical sleeve gastrectomy. This article focuses on the preoperative evaluation and proper patient selection for metabolic surgery. The procedures are discussed relative to their anatomy, metabolic mechanism of action, and common adverse effects. PMID- 26896209 TI - Just Eat Less and Exercise More? PMID- 26896208 TI - Behavioral Modification for the Management of Obesity. AB - This article provides behavioral strategies for working with obese patients and families within a primary care context. A multifactorial model for the etiology of obesity from which to adopt treatment strategies is provided. Optimal views to set up effective patient encounters and specific recommendations to motivate and support patients are discussed. Multicomponent programs include a combination of nutritional, physical activity, and cognitive behavioral approaches to target overweight/obesity. The focus is on behavioral approaches and practical applications, such as motivational interviewing techniques. PMID- 26896210 TI - Obesity: A Plague Upon Our Houses. PMID- 26896211 TI - Adolescent Reproductive Knowledge, Attitudes, and Beliefs and Future Fatherhood. AB - PURPOSE: With a growing focus on the importance of men's reproductive health, including preconception health, the ways in which young men's knowledge, attitudes, and beliefs (KAB) predict their reproductive paths are understudied. To determine if reproductive KAB predicts fatherhood status, timing and residency (living with child or not). METHODS: Reproductive KAB and fatherhood outcomes were analyzed from the National Longitudinal Study of Adolescent Health, a 20 year, nationally representative study of individuals from adolescence into adulthood. Four measures of reproductive KAB were assessed during adolescence in waves I and II. A generalized linear latent and mixed model predicted future fatherhood status (nonfather, resident/nonresident father, adolescent father) and timing while controlling for other socio-demographic variables. RESULTS: Of the 10,253 men, 3,425 were fathers (686 nonresident/2,739 resident) by wave IV. Higher risky sexual behavior scores significantly increased the odds of becoming nonresident father (odds ratio [OR], 1.30; p < .0001), resident father (OR, 1.07; p = .007), and adolescent father (OR, 1.71; p < .0001); higher pregnancy attitudes scores significantly increased the odds of becoming a nonresident father (OR, 1.20; p < .0001) and resident father (OR, 1.11; p < .0001); higher birth control self-efficacy scores significantly decreased the odds of becoming a nonresident father (OR, .72; p < .0001) and adolescent father (OR, .56; p = .01). CONCLUSIONS: Young men's KAB in adolescence predicts their future fatherhood and residency status. Strategies that address adolescent males' reproductive KAB are needed in the prevention of unintended reproductive consequences such as early and nonresident fatherhood. PMID- 26896214 TI - Saving 2 lives with 1 operation! PMID- 26896213 TI - Perioperative outcomes with sutureless versus stented biological aortic valves in elderly persons. AB - OBJECTIVES: Sutureless aortic valves are deemed suitable for patients considered at high risk for surgery. The objective of this study is to evaluate the perioperative results of implanting a sutureless valve in elderly persons, compared with a stented biological valve in the aortic position. METHODS: Between 2011 and 2015, 76 patients underwent aortic valve replacement with the Perceval prosthesis (Sorin Group, Saluggia, Italy). The group was compared with 319 consecutive patients who received aortic valve replacement with the stented valve in that same period. RESULTS: The mean age of patients was 83 +/- 2 years in the Perceval group and 83 +/- 3 years in the stented valve group (P = .3). Preoperative demographics were similar in both groups. Median cardiopulmonary bypass and crossclamp times were lower in the Perceval group than in the stented valve group (P < .001). Mortality was 5% in the Perceval group and 6% in the stented valve group (P = .8). There were more pacemaker implantations in the Perceval group than in the stented valve group (17% vs 8%; P = .02). A subgroup analysis of patients who underwent aortic valve replacement and concomitant procedures showed the same results as the entire cohort. CONCLUSIONS: Aortic valve replacement with a sutureless prosthesis resulted in shorter aortic crossclamp and bypass times compared with a stented biological prosthesis. The reduced cardiopulmonary bypass and aortic crossclamp times obtained using the Perceval prosthesis did not translate into perioperative gains in our population of elderly patients. PMID- 26896215 TI - Pushing the Envelope. PMID- 26896212 TI - Tamoxifen Administration Immediately or 24 Hours after Spinal Cord Injury Improves Locomotor Recovery and Reduces Secondary Damage in Female Rats. AB - Spinal cord injury (SCI) is a condition with no available cure. The initial physical impact triggers a cascade of molecular and cellular events that generate a nonpermissive environment for cell survival and axonal regeneration. Spinal cord injured patients often arrive at the clinic hours after the initial insult. This indicates the need to study and develop treatments with a long therapeutic window of action and multiactive properties, which target the complex set of events that arise after the initial trauma. We provide evidence that tamoxifen (TAM), a drug approved by the Food and Drug Administration, exerts neuroprotective effects in an animal model when applied up-to 24 h after SCI. We hypothesized that continuous TAM administration will improve functional locomotor recovery by favoring myelin preservation and reducing secondary damage after SCI. Adult female Sprague-Dawley rats (~230 g) received a moderate contusion to the thoracic (T9-T10) spinal cord, using the MASCIS impactor device. To determine the therapeutic window available for TAM treatment, rats were implanted with TAM pellets (15 mg) immediately or 24 h after SCI. Locomotor function (Basso, Beattie, Bresnahan open field test, grid walk, and beam crossing tests) was assessed weekly for 35 days post-injury. TAM-treated rats showed significant functional locomotor recovery and improved fine movements when treated immediately or 24 h after SCI. Further, TAM increased white matter preservation and reduced secondary damage caused by astrogliosis, axonal degeneration, and cell death after trauma. These results provide evidence for TAM as a potential therapeutic agent to treat SCI up to 24 h after the trauma. PMID- 26896216 TI - Challenging Return to Play Decisions: Heat Stroke, Exertional Rhabdomyolysis, and Exertional Collapse Associated With Sickle Cell Trait. AB - CONTEXT: Sports medicine providers frequently return athletes to play after sports-related injuries and conditions. Many of these conditions have guidelines or medical evidence to guide the decision-making process. Occasionally, however, sports medicine providers are challenged with complex medical conditions for which there is little evidence-based guidance and physicians are instructed to individualize treatment; included in this group of conditions are exertional heat stroke (EHS), exertional rhabdomyolysis (ER), and exertional collapse associated with sickle cell trait (ECAST). EVIDENCE ACQUISITION: The MEDLINE (2000-2015) database was searched using the following search terms: exertional heat stroke, exertional rhabdomyolysis, and exertional collapse associated with sickle cell trait. References from consensus statements, review articles, and book chapters were also utilized. STUDY DESIGN: Clinical review. LEVEL OF EVIDENCE: Level 4. RESULTS: These entities are unique in that they may cause organ system damage capable of leading to short- or long-term detriments to physical activity and may not lend to complete recovery, potentially putting the athlete at risk with premature return to play. CONCLUSION: With a better understanding of the pathophysiology of EHS, ER, and ECAST and the factors associated with recovery, better decisions regarding return to play may be made. PMID- 26896219 TI - Pretransplantation Imaging Workup of the Liver Donor and Recipient. AB - Liver transplantation requires thorough preoperative imaging. Contrast enhanced computed tomography (CT) and MR imaging are the main modalities utilized for this purpose. Radiation-reducing protocols, advanced imaging techniques for evaluation of parenchymal fat and iron content, and 3-dimenionsal and volumetric reformations are routinely used. The helpful diagnostic radiologist has a complete understanding of indications for transplant, the indications for bridging and/or down-staging therapies for hepatocellular carcinoma, and the components of the transplant operation. With this information at hand, the radiologist can craft a thorough, yet succinct report that will help the surgeon plan and execute successful donor and recipient transplant operations. PMID- 26896217 TI - Is the Marx Activity Scale Reliable in Patients Younger Than 18 Years? AB - BACKGROUND: There is no baseline activity scale yet validated in pediatric patients. The Marx and Tegner scales have been validated in adult patients only. The Tegner scale involves questions not pertinent to children, such as their work activity. The Marx scale is simple, and all its questions can be related to athletic activities. HYPOTHESIS: The Marx scale is reliable for use in a pediatric population. STUDY DESIGN: Cohort study. LEVEL OF EVIDENCE: Level 2. METHODS: Patients younger than 18 years were given the Marx activity scale in clinic and again 3 weeks later. The patients were divided into 3 groups, of at least 50 patients each, based on presenting diagnosis: knee injury, lower extremity (non-knee) injury, and upper extremity injury. Test-retest reliability was determined for the overall scores and the individual questions. Differences in scores were also compared based on age (<14 vs >=14 years). RESULTS: A total of 162 patients (mean age, 14.4 years; range, 8-17 years) were included. The Marx scale had a high intraclass correlation coefficient (ICC) overall as well as for each of its 4 questions. Both older and younger patients had ICCs >0.80, though the older group generally had higher scores. The mean score was 13.55 (out of 16), and 50.6% scored the maximum; only 1.9% scored the minimum. Mean scores for the knee, lower extremity, and upper extremity groups were 13.71 (SD, 3.70), 13.22 (SD, 4.18), and 13.68 (SD, 3.33), respectively (P > 0.05). There also was no difference in total score based on age (P = 0.88). CONCLUSION: The Marx activity scale is reliable in patients younger than 18 years with injuries to the knee and lower extremities, though the scale was less reliable in patients younger than 14 years. There is a significant ceiling effect present, which limits its overall usefulness. CLINICAL RELEVANCE: Although there is no other current substitute, the Marx activity scale is not an ideal measurement of younger patients' baseline activity levels. PMID- 26896220 TI - Surgical Techniques and Imaging Complications of Liver Transplant. AB - Liver transplant is the treatment of choice for end-stage liver disease. Management of transplant patients requires a multidisciplinary approach, with radiologists playing a key role in identifying complications in both symptomatic and asymptomatic patients. Ultrasonography remains the investigation of choice for the initial evaluation of symptomatic patients. Depending on the clinical situation, further evaluation with CT, MRI, or biopsy may be performed or clinical and imaging surveillance may be continued. This article discusses the various normal and abnormal imaging presentations of liver transplant patients, including various acute and chronic complications, and their management. PMID- 26896221 TI - Renal Pretransplantation Work-up, Donor, Recipient, Surgical Techniques. AB - Renal transplant is the single best treatment of end-stage renal disease. Computed tomography (CT) is an excellent method for the evaluation of potential renal donors and recipients. Multiphase CT is particularly useful because of detailed evaluation of the kidneys, including the vascular anatomy and the collecting system. MR imaging has no ionizing radiation, but is limited for stone detection, making it a less preferred method of evaluating donors. Preoperative knowledge of the renal vascular anatomy is essential to minimize risks for donors. Imaging evaluation of recipients is also necessary for vascular assessment and detection of incidental findings. PMID- 26896222 TI - Imaging Complications of Renal Transplantation. AB - Renal transplant complications are categorized as those related to the transplant vasculature, collecting system, perinephric space, renal parenchyma, and miscellaneous complications including posttransplant lymphoproliferative disorder. Many of these renal transplant complications are diagnosed with imaging. Medical complications including rejection, acute tubular necrosis, and drug toxicity also can impair renal function. These medical complications are typically indistinguishable at imaging, and biopsy may be performed to establish a diagnosis. Normal transplant anatomy, imaging techniques, and the appearances of renal transplant complications at ultrasound, computed tomography, and MR imaging are reviewed. PMID- 26896223 TI - Imaging of Pancreas Transplantation and Its Complications. AB - Whole pancreas transplantation is an effective treatment for obtaining euglycemic status in patients with insulin-dependent diabetes mellitus, and is usually performed concurrent with renal transplantation in the affected patient. This article discusses complex surgical anatomical details of pancreas transplantation including surgical options for endocrine and exocrine drainage pathways. It then describes several possible complications related to surgical factors in the immediate post operative period followed by other complications related to systemic issues, vasculature, and the pancreatic parenchyma. PMID- 26896224 TI - Interventional and Surgical Techniques in Solid Organ Transplantation. AB - Liver, kidney, and pancreas transplants are complex procedures that have evolved over the past several decades from pioneering, experimental procedures into well developed, refined procedures that have saved countless lives. Previously encountered technical, immunologic, and perioperative obstacles have now been overcome and improved upon, allowing for the success of these procedures today. This article reviews the basic surgical techniques used for solid organ transplantation that are relevant to, and are currently encountered by radiologists. This article also reviews commonly encountered postoperative complications, and the techniques and strategies that have evolved in interventional radiology to overcome these complications. PMID- 26896225 TI - Pediatric Abdominal Organ Transplantation: Current Indications, Techniques, and Imaging Findings. AB - The anatomy, normal postoperative radiological appearance, and imaging features of common postoperative complications of pediatric abdominal transplants are reviewed, including renal, liver, and intestinal transplants. Doppler ultrasound is the mainstay of imaging after transplantation. Computed tomography (CT) and CT angiography, MR imaging and magnetic resonance (MR) angiography, MR cholangiopancreatography, conventional angiography, and nuclear medicine imaging may be used for problem-solving in pediatric transplant patients. Accurate and timely radiological diagnosis of transplant complications facilitates appropriate treatment and minimizes morbidity and mortality. PMID- 26896226 TI - Complications of Immunosuppressive Therapy in Solid Organ Transplantation. AB - Availability of novel immunosuppressive drugs is the most important factor responsible for significant improvement in long-term graft survival rates after solid organ transplantation. However, chronic immunosuppression predisposes patients to a myriad of potentially life-threatening complications. In addition to drug-related adverse effects, transplant recipients are at increased risk of developing opportunistic microbial infections and a spectrum of unique cancers, many of which are caused by oncogenic viruses. Cross-sectional imaging studies play a crucial role in the timely diagnosis and management of post-transplant infections and malignancies. PMID- 26896227 TI - Pediatric Thoracic Organ Transplantation: Current Indications, Techniques, and Imaging Findings. AB - In the past decade, with improved surgical technique and knowledge of immunosuppression, pediatric lung and heart transplantation have been established as viable therapeutic interventions for pediatric patients with end-stage cardiopulmonary disease from various underlying congenital and acquired disorders. Although outcomes for pediatric patients are similar to those for adult patients, thoracic organ transplantation in this special age group carries unique challenges for preoperative and postoperative imaging evaluation. The article provides an up-to-date review of the postoperative transplant anatomy, imaging techniques, and complications of pediatric lung and heart transplantation. PMID- 26896228 TI - Imaging in Lung Transplantation: Surgical Considerations of Donor and Recipient. AB - Modifications in recipient and donor criteria and innovations in donor management hold promise for increasing rates of lung transplantation, yet availability of donors remains a limiting resource. Imaging is critical in the work-up of donor and recipient including identification of conditions that may portend to poor posttransplant outcomes or necessitate modifications in surgical technique. This article describes the radiologic principles that guide selection of patients and surgical procedures in lung transplantation. PMID- 26896229 TI - Imaging the Complications of Lung Transplantation. AB - Imaging plays a key role in the diagnosis and management of complications following lung transplantation. This article outlines the imaging modalities available for evaluation of posttransplant complications with a focus on major indications and key strengths and weaknesses of each modality. A brief description of surgical technique and relevant anatomy is included. Descriptions of some of the more commonly encountered complications are outlined with a focus on imaging findings. Complications are grouped by anatomic or imaging-based findings and subcategorized chronologically to help order the differential diagnosis. PMID- 26896230 TI - Current Indications, Techniques, and Imaging Findings of Stem Cell Treatment and Bone Marrow Transplant. AB - The role of stem cell therapy in the treatment of hematologic and nonhematologic conditions is ever increasing. A thorough knowledge of the applications of stem cells and transplant physiology is essential for understanding the imaging manifestations. Stem cell imaging includes molecular imaging, and diagnostic and interventional radiology. It is possible to make a diagnosis of various complications and diseases associated with stem cell transplant. This article presents a simplified overview of stem cell applications and techniques with focus on hematopoietic stem cell transplant imaging. PMID- 26896231 TI - Transplant Imaging--Focusing on a Systematic Approach. PMID- 26896233 TI - Effects of different amounts and types of dietary fatty acids on the body weight, fat accumulation, and lipid metabolism in hamsters. AB - OBJECTIVES: The aim of this study was to explore the effects of different amounts of dietary fatty acids on body weight, fat accumulation, and lipid metabolism of hamsters. METHODS: Sixty male golden Syrian hamsters were randomly divided into six groups. Three of the groups (the S groups) were fed experimental diets containing 5%, 15%, and 20% (w/w) fat of soybean oil (S5, S15, and S20, respectively), and the other three groups (the M groups) were fed the same proportions of an experimental oil mixture (M5, M15, and M20, respectively). The experimental oil mixture consisted of 60% monounsaturated fatty acids (MUFAs) and a polyunsaturated-to-saturated fatty acid ratio of 5 with a mixture of soybean and canola oils. Food consumption was measured daily, and body weights were measured weekly. Serum insulin and leptin concentrations were measured and hepatic fatty acid metabolic enzymes and adipose differentiation markers were determined using an enzyme activity analysis and quantitative polymerase chain reaction. RESULTS: Results showed that the weight and weight gain of the S20 group were significantly greater than those of the other five groups. When the total fat consumption increased, the body weight, weight gain, and adipose tissue weight of the S groups significantly increased, but there were no significant differences in these parameters among the M groups. Serum low-density lipoprotein cholesterol concentrations were significantly lower in the M15 and S15 groups. The S20 group had significantly higher leptin and insulin concentrations and lipoprotein lipase was promoted, but the acetyl-coenzyme A oxidase and carnitine palmitoyltransferase-1, were significantly lower. CONCLUSIONS: The study demonstrated that a special experimental oil mixture (with 60% MUFAs and a ratio of 5) with high fat can prevent body weight gain and body fat accumulation by lowering insulin concentrations and increasing hepatic lipolytic enzyme activities. PMID- 26896234 TI - Biodegradable scaffolds designed to mimic fascia-like properties for the treatment of pelvic organ prolapse and stress urinary incontinence. AB - There is an urgent clinical need for better synthetic materials to be used in surgical support of the pelvic floor. The aim of the current study was to construct biodegradable synthetic scaffolds that mimic the three-dimensional architecture of human fascia, which can integrate better into host tissues both mechanically and biologically. Therefore, four different polylactic acid (PLA) scaffolds with various degrees of fibre alignment were electrospun by modifying the electrospinning parameters. Physical and mechanical properties were assessed using a BOSE electroforce tensiometer. The attachment, viability and extracellular matrix production of adipose-derived stem cells cultured on the polylactic acid scaffolds were evaluated. The bulk density of the scaffolds decreased as the proportion of aligned fibres increased. Scaffolds became stronger and stiffer with increasing amounts of aligned fibres as measured along the axis parallel to the fibre alignment. In addition, more total collagen was produced on scaffolds with aligned fibres and was organised in the direction of the aligned fibres. In conclusion, the electrospinning technique can be easily modified to develop biodegradable scaffolds with a spectrum of mechanical properties allowing extracellular matrix organisation towards human-like fascia. PMID- 26896232 TI - Enquiring About Tolerance (EAT) study: Feasibility of an early allergenic food introduction regimen. AB - BACKGROUND: The influence of early exposure to allergenic foods on the subsequent development of food allergy remains uncertain. OBJECTIVE: We sought to determine the feasibility of the early introduction of multiple allergenic foods to exclusively breast-fed infants from 3 months of age and the effect on breastfeeding performance. METHODS: We performed a randomized controlled trial. The early introduction group (EIG) continued breastfeeding with sequential introduction of 6 allergenic foods: cow's milk, peanut, hard-boiled hen's egg, sesame, whitefish (cod), and wheat; the standard introduction group followed the UK infant feeding recommendations of exclusive breastfeeding for around 6 months with no introduction of allergenic foods before 6 months of age. RESULTS: One thousand three hundred three infants were enrolled. By 5 months of age, the median frequency of consumption of all 6 foods was 2 to 3 times per week for every food in the EIG and no consumption for every food in the standard introduction group (P < .001 for every comparison). By 6 months of age, nonintroduction of the allergenic foods in the EIG was less than 5% for each of the 6 foods. Achievement of the stringent per-protocol consumption target for the EIG proved more difficult (42% of evaluable EIG participants). Breastfeeding rates in both groups significantly exceeded UK government data for equivalent mothers (P < .001 at 6 and at 9 months of age). CONCLUSION: Early introduction, before 6 months of age, of at least some amount of multiple allergenic foods appears achievable and did not affect breastfeeding. This has important implications for the evaluation of food allergy prevention strategies. PMID- 26896235 TI - Investigation of the in vitro photocatalytic antibacterial activity of nanocrystalline TiO2 and coupled TiO2/Ag containing copolymer on the surface of medical grade titanium. AB - Antibacterial surfaces have been in the focus of research for years, driven by an unmet clinical need to manage an increasing incidence of implant-associated infections. The use of silver has become a topic of interest because of its proven broad-spectrum antibacterial activity and track record as a coating agent of soft tissue implants and catheters. However, for the time being, the translation of these technological achievements for the improvement of the antibacterial property of hard tissue titanium (Ti) implants remains unsolved. In our study, we focused on the investigation of the photocatalysis mediated antibacterial activity of silver (Ag), and Ti nanoparticles instead of their pharmacological effects. We found that the photosensitisation of commercially pure titanium discs by coating them with an acrylate-based copolymer that embeds coupled Ag/Ti nanoparticles can initiate the photocatalytic decomposition of adsorbed S. salivarius after the irradiation with an ordinary visible light source. The clinical isolate of S. salivarius was characterised with MALDI-TOF mass spectrometer, while the multiplication of the bacteria on the surface of the discs was followed-up by MTT assay. Concerning practical relevance, the infected implant surfaces can be made accessible and irradiated by dental curing units with LED and plasma arc light sources, our research suggests that photocatalytic copolymer coating films may offer a promising solution for the improvement of the antibacterial properties of dental implants. PMID- 26896236 TI - Subcutaneous meloxicam suspension pharmacokinetics in mice and dose considerations for postoperative analgesia. AB - Meloxicam is a cyclooxygenase (COX) inhibitor with a higher selectivity for cyclooxygenase-2 (COX-2) than for cyclooxygenase-1 (COX-1). In the laboratory setting, this nonsteroidal anti-inflammatory drug (NSAID) is commonly selected for analgesia in mice and administered every 24 h. This study characterizes the plasma concentration achieved from a dose of 1.6 mg/kg of meloxicam administered once every 24 h subcutaneously for 72 h in male and female C57BL/6 mice. These values were compared, over time, to reference COX-2 inhibition constants for meloxicam. No significant differences in trough plasma concentrations were noted between genders. The plasma concentrations were below the COX-2 IC50 after 12 h. To maintain a plasma concentration at or above the COX-2 whole blood IC50, the study results suggest an administration frequency of every 12 h when using a dose of 1.6 mg/kg in C57BL/6 mice. PMID- 26896237 TI - Stage of breast cancer at diagnosis in New Zealand: impacts of socio-demographic factors, breast cancer screening and biology. AB - BACKGROUND: Examination of factors associated with late stage diagnosis of breast cancer is useful to identify areas which are amenable to intervention. This study analyses trends in cancer stage at diagnosis and impact of socio-demographic, cancer biological and screening characteristics on cancer stage in a population based series of women with invasive breast cancer in New Zealand. METHODS: All women diagnosed with invasive breast cancer between 2000 and 2013 were identified from two regional breast cancer registries. Factors associated with advanced (stages III and IV) and metastatic (stage IV) cancer at diagnosis were analysed in univariate and multivariate models adjusting for covariates. RESULTS: Of the 12390 women included in this study 2448 (19.7%) were advanced and 575 (4.6%) were metastatic at diagnosis. Maori (OR = 1.86, 1.39-2.49) and Pacific (OR = 2.81, 2.03-3.87) compared with NZ European ethnicity, other urban (OR = 2.00, 1.37 2.92) compared with main urban residency and non-screen (OR = 6.03, 4.41-8.24) compared with screen detection were significantly associated with metastatic cancer at diagnosis in multivariate analysis. A steady increase in the rate of metastatic cancer was seen which has increased from 3.8% during 2000-2003 to 5.0% during 2010-2013 period (p = 0.042). CONCLUSIONS: Providing equitable high quality primary care and increasing mammographic screening coverage needs to be looked at as possible avenues to reduce late-stage cancer at diagnosis and to reduce ethnic, socioeconomic and geographical disparities in stage of breast cancer at diagnosis in New Zealand. PMID- 26896238 TI - beta2-Adrenoceptor is involved in connective tissue remodeling in regenerating muscles by decreasing the activity of MMP-9. AB - We investigated the role of beta2-adrenoceptors in the connective tissue remodeling of regenerating muscles from beta2-adrenoceptor knockout (beta2KO) mice. Tibialis anterior muscles from beta2KO mice were cryolesioned and analyzed after 3, 10, and 21 days. Regenerating muscles from beta2KO mice showed a significant increase in the area density of the connective tissue and in the amount of collagen at 10 days compared with wild-type (WT) mice. A greater increase occurred in the expression levels of collagen I, III, and IV in regenerating muscles from beta2KO mice evaluated at 10 days compared with WT mice; this increase continued at 21 days, except for collagen III. Matrix metalloproteinase (MMP-2) activity increased to a similar extent in regenerating muscles from both beta2KO and WT mice at 3 and 10 days. This was also the case for MMP-9 activity in regenerating muscles from both beta2KO and WT mice at 3 days; however, at 10 days post-cryolesion, this activity returned to baseline levels only in WT mice. MMP-3 activity was unaltered in regenerating muscles at 10 days. mRNA levels of tumor necrosis factor-alpha increased in regenerating muscles from WT and beta2KO mice at 3 days and, at 10 days post-cryolesion, returned to baseline only in WT mice. mRNA levels of interleukin-6 increased in muscles from WT mice at 3 days post-cryolesion and returned to baseline at 10 days post-cryolesion but were unchanged in beta2KO mice. Our results suggest that the beta2-adrenoceptor contributes to collagen remodeling during muscle regeneration by decreasing MMP-9 activity. PMID- 26896240 TI - Does this patient have hypertensive encephalopathy? AB - A 63-year-old man was admitted to our hospital for further investigation and management of brain metastases. The patient was initially presented with a 4-day history of confusion. On the day of admission, the patient was confused, agitated, disorientated in place and time, and had visual disturbances. His blood pressure was repeatedly recorded high, with levels of systolic blood pressure between 170-210 mm Hg. A brain magnetic resonance imaging showed areas of high signal on T2 and fluid-attenuated inversion recovery images, located bilaterally in the white matter of the occipital regions and unilateral in the left frontal lobe, suggestive of posterior reversible encephalopathy syndrome. Aggressive treatment of hypertension resulted in complete resolution of the clinical and radiologic features of the syndrome. PMID- 26896239 TI - Roseomonas chloroacetimidivorans sp. nov., a chloroacetamide herbicide-degrading bacterium isolated from activated sludge. AB - A Gram-negative, aerobic, short rod-shaped, pink-pigmented, non-motile bacterium, designated BUT-13(T), was isolated from activated sludge of an herbicide manufacturing wastewater treatment facility in Jiangsu province, China. Growth was observed at 0-5.5 % NaCl, pH 6.0-9.0 and 12-37 degrees C. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain BUT-13(T) is a member of the genus Roseomonas, and shows high sequence similarities to R. pecuniae N75(T) (98.0 %) and R. rosea 173-96(T) (97.5 %), and lower (<97 %) sequence similarities to all other Roseomonas species. Chemotaxonomic analysis revealed that strain BUT-13(T) possesses Q-10 as the predominant ubiquinone; summed feature 8 (C18:1 w7c and/or C18:1 w6c; 38.8 %), C18:0 (16.6 %), C16:0 (15.2 %), summed feature 3 (C16:1 omega6c and/or C16:1 omega7; 7.9 %) and C18:1 w9c (4.7 %) as the major fatty acids. The polar lipids were found to consist of two aminolipids, a glycolipid, a phospholipid, a phosphoglycolipid, phosphatidylcholine, phosphatidylethanolamine and diphosphatidylglycerol. Strain BUT-13(T) showed low DNA-DNA relatedness with R. pecuniae N75(T) (45.2 %) and R. rosea 173-96(T) (51.2 %). The DNA G+C content was determined to be 67.6 mol%. Based on the phylogenetic analysis, DNA-DNA hybridization and chemotaxonomic analysis, as well as biochemical characteristics, strain BUT-13(T) can be clearly distinguished from all currently recognised Roseomonas species and should be classified as a novel species of the genus Roseomonas, for which the name Roseomonas chloroacetimidivorans sp. nov. is proposed. The type strain is BUT 13(T) (CCTCC AB 2015299(T) = JCM 31050(T)). PMID- 26896241 TI - Improved low-cost, MR-compatible olfactometer to deliver tobacco smoke odor. AB - We describe a low-cost, MRI-compatible olfactometer that delivers fresh cigarette smoke odor, a challenging odorant to present, as well as other odorants. This new olfactometer retains all of the advantages of an earlier design that was capable of only delivering volatile odors (Lowen & Lukas, Behavior Research Methods, 38, 307-313, 2006). The new system incorporates a novel switching mechanism that allows it to deliver fresh smoke generated from a burning cigarette during a stimulus presentation paradigm that might be employed in a cue-reactivity experiment. An evaluation study established that the olfactometer reliably delivered smoke to the participants and that tobacco smoke was discriminated from other odorants; there were no adverse reactions to the device. PMID- 26896242 TI - A cage-based training, cognitive testing and enrichment system optimized for rhesus macaques in neuroscience research. AB - In neurophysiological studies with awake non-human primates (NHP), it is typically necessary to train the animals over a prolonged period of time on a behavioral paradigm before the actual data collection takes place. Rhesus monkeys (Macaca mulatta) are the most widely used primate animal models in system neuroscience. Inspired by existing joystick- or touch-screen-based systems designed for a variety of monkey species, we built and successfully employed a stand-alone cage-based training and testing system for rhesus monkeys (eXperimental Behavioral Intrument, XBI). The XBI is mobile and easy to handle by both experts and non-experts; animals can work with only minimal physical restraints, yet the ergonomic design successfully encourages stereotypical postures with a consistent positioning of the head relative to the screen. The XBI allows computer-controlled training of the monkeys with a large variety of behavioral tasks and reward protocols typically used in systems and cognitive neuroscience research. PMID- 26896243 TI - Statokinesigram normalization method. AB - Stabilometry is a technique that aims to study the body sway of human subjects, employing a force platform. The signal obtained from this technique refers to the position of the foot base ground-reaction vector, known as the center of pressure (CoP). The parameters calculated from the signal are used to quantify the displacement of the CoP over time; there is a large variability, both between and within subjects, which prevents the definition of normative values. The intersubject variability is related to differences between subjects in terms of their anthropometry, in conjunction with their muscle activation patterns (biomechanics); and the intrasubject variability can be caused by a learning effect or fatigue. Age and foot placement on the platform are also known to influence variability. Normalization is the main method used to decrease this variability and to bring distributions of adjusted values into alignment. In 1996, O'Malley proposed three normalization techniques to eliminate the effect of age and anthropometric factors from temporal-distance parameters of gait. These techniques were adopted to normalize the stabilometric signal by some authors. This paper proposes a new method of normalization of stabilometric signals to be applied in balance studies. The method was applied to a data set collected in a previous study, and the results of normalized and nonnormalized signals were compared. The results showed that the new method, if used in a well-designed experiment, can eliminate undesirable correlations between the analyzed parameters and the subjects' characteristics and show only the experimental conditions' effects. PMID- 26896244 TI - Somatosensory cortex excitability: a child is not a small adult. PMID- 26896245 TI - Health-Related Quality of Life Among Jordanian Adolescents. AB - Adolescence is an unpredictable stage of life with varied and rapid changes. In Jordan, health-related quality of life (HRQoL) has been examined among diabetic and obese children and adolescents. The purpose of this study was to assess the HRQoL of Jordanian healthy adolescents. Three hundred fifty-four male and female adolescents whose ages ranged from 12 to 19 participated in the study. A descriptive comparative design was employed to investigate adolescents' HRQoL. The results revealed statistically significant differences in physical well being, psychosocial well-being, and autonomy in favor of male adolescents. In addition, statistically significant differences were observed in favor of nonsmoker adolescents in psychosocial well-being, self-perception, parent relations and home life, financial resources, social relations and peers and school environment. In conclusion, the creation of a school health nurse role in Jordanian schools is crucial for helping adolescents improve their health. PMID- 26896247 TI - Treatment of microvascular angina: the need for precision medicine. PMID- 26896248 TI - Hastened aortic valve surgery due to calcific retinal embolus in an asymptomatic patient with bicuspid aortic valvular disease. PMID- 26896249 TI - Detection of pulmonary arteriovenous fistula with three-dimensional computed tomographic angiography. PMID- 26896250 TI - Monoclonal antibodies targeting PCSK9 and the search for prolonged duration of effect. PMID- 26896246 TI - Probing the Complexities of Astrocyte Calcium Signaling. AB - Astrocytes are abundant glial cells that tile the entire central nervous system and mediate well-established functions for neurons, blood vessels, and other glia. These ubiquitous cells display intracellular Ca(2+) signals, which have been intensely studied for 25 years. Recently, the use of improved methods has unearthed the panoply of astrocyte Ca(2+) signals and a variable landscape of basal Ca(2+) levels. In vivo studies have started to reveal the settings under which astrocytes display behaviorally relevant Ca(2+) signaling. Studies in mice have emphasized how astrocyte Ca(2+) signaling is altered in distinct neurodegenerative diseases. Progress in the past few years, fueled by methodological advances, has thus reignited interest in astrocyte Ca(2+) signaling for brain function and dysfunction. PMID- 26896251 TI - The incarcerated heart: porcelain cage. PMID- 26896252 TI - Blood cadmium level in the elderly population: perspective for the cause of inconsistent results. PMID- 26896254 TI - What next for the junior doctor contract? PMID- 26896253 TI - Heavy manual work throughout the working lifetime and muscle strength among men at retirement age. AB - INTRODUCTION: Reductions in heavy manual work as a consequence of mechanisation might adversely impact muscle strength at older ages. We investigated the association between grip strength at retirement age and lifetime occupational exposure to physically demanding activities. Grip strength is an important predictor of long-term health and physical function in older people. METHODS: Grip strength (maximum of three readings in each hand) was measured in men from the Hertfordshire Cohort Study at a single examination when their mean age was 65.8 (SD 2.9) years. Associations with lifetime occupational exposure (ascertained by questionnaire) to three activities (standing/walking >= 4 h/day; lifting >= 25 kg; and energetic work sufficient to induce sweating) were assessed by multivariable linear regression with adjustment for various potential confounders. RESULTS: Complete data were available from 1418 men who had worked for at least 20 years. After adjustment for age, height and weight, those with longer exposures to walking/standing and heavy lifting had lower grip strength, but the relationship disappeared after further adjustment for confounders. Working at physical intensity sufficient to induce sweating was not significantly associated with grip strength. CONCLUSIONS: We found no evidence that physically demanding occupational activities increase hand grip strength at normal retirement age. Any advantages of regular physical occupational activity may have been obscured by unmeasured socioeconomic confounders. PMID- 26896255 TI - When doctors start civil disobedience it's time to take notice. PMID- 26896256 TI - Evaluating In Vivo-In Vitro Correlation Using a Bayesian Approach. AB - A Bayesian approach with frequentist validity has been developed to support inferences derived from a "Level A" in vivo-in vitro correlation (IVIVC). Irrespective of whether the in vivo data reflect in vivo dissolution or absorption, the IVIVC is typically assessed using a linear regression model. Confidence intervals are generally used to describe the uncertainty around the model. While the confidence intervals can describe population-level variability, it does not address the individual-level variability. Thus, there remains an inability to define a range of individual-level drug concentration-time profiles across a population based upon the "Level A" predictions. This individual-level prediction is distinct from what can be accomplished by a traditional linear regression approach where the focus of the statistical assessment is at a marginal rather than an individual level. The objective of this study is to develop a hierarchical Bayesian method for evaluation of IVIVC, incorporating both the individual- and population-level variability, and to use this method to derive Bayesian tolerance intervals with matching priors that have frequentist validity in evaluating an IVIVC. In so doing, we can now generate population profiles that incorporate not only variability in subject pharmacokinetics but also the variability in the in vivo product performance. PMID- 26896258 TI - Inadequate investment in school health education: A missed opportunity. PMID- 26896257 TI - Balancing idealism with realism to safeguard the welfare of patients: The importance of Heart Team led decision-making in patients with complex coronary artery disease. PMID- 26896259 TI - Relationship of high altitude and congenital heart disease. PMID- 26896260 TI - Emergence of cardiometabolic risk in Bangladesh. PMID- 26896261 TI - Heart-type fatty acid-binding protein (H-FABP) and coronary heart disease. PMID- 26896262 TI - Does modern medicine increase life-expectancy: Quest for the Moon Rabbit? AB - The search for elixir of immortality has yielded mixed results. While some of the interventions like percutaneous coronary interventions and coronary artery bypass grafting have been a huge disappointment at least as far as prolongation of life is concerned, their absolute benefit is meager and that too in very sick patients. Cardiac specific drugs like statins and aspirin have fared slightly better, being useful in patients with manifest coronary artery disease, particularly in sicker populations although even their usefulness in primary prevention is rather low. The only strategies of proven benefit in primary/primordial prevention are pursuing a healthy life-style and its modification when appropriate, like cessation of smoking, weight reduction, increasing physical activity, eating a healthy diet and bringing blood pressure, serum cholesterol, and blood glucose under control. PMID- 26896264 TI - Left main PCI: An observational analysis from large single-centre experience. AB - BACKGROUND: Although trials have shown efficacy of unprotected left main percutaneous coronary intervention (uLMPCI), data from Indian subcontinent are lacking. Hence, we planned this observational analysis of single-center uLMPCI data. OBJECTIVES: To study long-term outcome after uLMPCI and identify predictors of adverse outcome. METHODS: Case details of 62 consecutive patients of uLMPCI between 2006 and 2013 were retrieved from a computerized database wherein detailed records were maintained. RESULTS: Mean follow-up duration was 669.8+/ 404.2 days. Procedural success rate was 98.4%. Primary endpoint was composite of major adverse cardiovascular and cerebrovascular events (MACCE), which included cardiac death (CD), cerebrovascular accident (CVA), myocardial infarction (MI), and need for repeat intervention (RI) at three years. MACCE occurred in 13 (20.9%) patients. Cardiac death (CD), (including possible stent thrombosis), RI, and CVA occurred in 6 (9.7%), 5 (8%), and 2 (3.2%) patients, respectively. Overall three-year MACCE-free survival rate was 76.7%. Event-free survival rate was similar among patients who underwent uLMPCI alone and patients who underwent uLMPCI along with additional one-vessel PCI [(88.9% vs 81.8%), p=0.492], while survival rate was lower in patients who underwent uLMPCI along with PCI of additional two or more vessels (40%, p=0.036). Patients with syntax score <=32 had higher event-free survival rate than those with syntax score >32 [(87.1% vs 33.3%), p=0.001]. Syntax score >32 was the only independent predictor of adverse outcome. CONCLUSION: uLMPCI is safe and effective alternative to CABG for LM alone and LM plus single-vessel disease with syntax score <=32. PMID- 26896263 TI - Angioplasty of unprotected left main coronary stenosis: Real world experience of a single-operator group from eastern India. AB - BACKGROUND: Coronary artery bypass graft surgery is the standard treatment of unprotected left main coronary stenosis (ULMCA). However, in the real world scenario, many of these patients are unfit for CABG or prefer angioplasty as an alternative when offered the choice. METHODS: A total of 86 clinically stable patients with ULMCA stenosis who were unfit or unwilling for CABG underwent PCI with DES at two tertiary care centers in Kolkata. Patients were followed up prospectively for a median of 34.6 months for major adverse cardiovascular events. Angiographic follow-up was done after 1 year of index procedure or earlier, if indicated. RESULTS: Fifty-five patients (64%) had distal left main stenosis. Two-stent technique was used in 19 patients (22%) and single-stent technique in 36 patients (42%) with distal left main lesion. Thirteen patients (15.1%) had left ventricular ejection fraction (LVEF) of <=45%. There was no in hospital death, MI, or stent thrombosis. During follow-up, major adverse cardiac event (MACE) occurred in 9 patients (10.5%). Our study revealed significantly greater MACE in patients with distal left main lesion with LVEF <=45% (50% vs 6.38%, p=0.0002), high SYNTAX score (36.36% vs 6.82%, p=0.008), and diabetes (17.95% vs 0.00%, p=0.07). Overall, also patients with Diabetes, LVEF <= 45%, and SYNTAX score >32 had significantly higher MACE. Use of IC Stent, IVUS, or procedural strategy in distal lesion did not affect MACE. CONCLUSION: In selective patients with low-intermediate SYNTAX score and without diabetes and LV dysfunction, ULMCA PCI with DES is feasible. PMID- 26896265 TI - Cardiovascular health awareness and the effect of an educational intervention on school-aged children in a rural district of India. AB - BACKGROUND AND OBJECTIVES: India is the second most populous country in the world and two-thirds of its population is less than 35 years old. This survey was conducted to assess the level of health awareness of cardiovascular disease in adolescent school-aged children 14-16 years old, with the goal of establishing school-based health education and development of heart-healthy lifestyle practices. METHODS: A school-based survey was conducted in the rural district of West Midnapore, India between June and July of 2014. This involved a pre evaluation of cardiovascular disease (CVD) health awareness, a short presentation on CVD, and a post-evaluation of CVD health awareness. RESULTS: A total of 2995 students (48% response rate) from 20 schools participated in the survey. The mean age of the students in the study sample was 14.7 years, 46% were male, 53% were in the 9th grade, and the rest were in the 10th grade. After assessing students' awareness in six domains with 20 multiple-choice questions with a maximum score of 100, the mean pre-test score was 41.1 (SD+/-10.5) and the mean post-test score was 48.1 (SD+/-16.9) (p<0.001). CONCLUSIONS: Awareness of CVD and its risk factors was far from optimal among the adolescent school-aged children in this study. A school-based educational program may help improve awareness of CVD and reduce the future disease burden in the community. The results of this study may be useful in formulating a nationwide school health program to deal with the emerging epidemic of CVD in countries such as India. PMID- 26896266 TI - Prevalence of congenital heart disease in rural population of Himachal - A population-based study. AB - AIM: There is no community-based study about the prevalence of congenital heart disease (CHD) in Himachal; hence, we undertook this study. METHODS AND RESULTS: A population-based survey was done in four villages of different districts of Himachal Pradesh. In total, 1882 persons were examined. 909 were male and 973 were female. There were 12 cases of CHD in the population (6.3/1000): four of these were male (33.3%) and 8 were female (66.6%). Mean age of these patients was 19.5+/-11.07 years. Atrial septal defect (ASD) was the commonest lesion followed by ventricular septal defect (VSD). CONCLUSION: Prevalence of CHD in general population was 6.3/1000. ASD was the commonest lesion. CHD was more common in female. PMID- 26896267 TI - Blood glucose and cholesterol levels in adult population of Bangladesh: Results from STEPS 2006 survey. AB - BACKGROUND: A nationally representative survey was carried out to determine the distribution of blood glucose and cholesterol in adult population of Bangladesh in the absence of existing data. METHODS: The study adopted a multistage and geographically clustered sampling technique of households. A total of 2610 individuals (1444 men and 1166 women) aged 25-64 years were selected from rural and urban areas. Capillary blood glucose and total cholesterol levels were measured using an overnight fasting state. RESULTS: The mean age of the participants was 41 years [standard deviation (SD), 11 years]. Half of them (49%) were from urban areas. Half of them (51%) had primary or higher education. Mean glucose was 74mg/dL (SD 23mg/dL). Men had higher mean glucose levels (79mg/dL) than women (67mg/dL). Age-standardized prevalence of diabetes (blood glucose level >=126mg/dL and/or use of anti-diabetic medication) was 5.5%. In men, it was almost two-and-half times (7.6%) compared with women (2.8%). It was also double in urban areas (7.8%) compared with rural areas (3.4%). Mean cholesterol level among all participants was 167mg/dL (SD 26mg/dL). Men and women had almost similar levels (169mg/dL versus 166mg/dL, respectively). Prevalence of high cholesterol level (>=240mg/dL) was very low (1.3%) in both men (2.2%) and women (0.5%). However, the prevalence of borderline high cholesterol was substantial (5.8%) in this sample. CONCLUSION: The prevalence of high hypercholesterolemia is low, whereas there is a high prevalence of borderline high cholesterol and diabetes in the adult population of Bangladesh. This warrants population-based interventions to tackle this problem. PMID- 26896269 TI - Pacemaker pocket infection due to environmental mycobacteria: Successful management of an outbreak and steps for prevention in future. AB - BACKGROUND: An outbreak of surgical site infection (SSI) due to environmental mycobacteria (EMB) occurred in a hospital in Eastern India. METHOD: A quality improvement project (QIP) was undertaken to analyze the causes and prevent further outbreak. Step (1) Proof of the need: Four patients who had undergone pacemaker implantation consecutively during a 10-day period developed SSI. Step (2) Diagnostic journey: Since all patients developed SSI within 2 months of implantation, a common source of infection was likely. Atypical mycobacteria (AMB) were grown from surgical sites as well as from the surface of operation table, image intensifier, and lead aprons. It was a rapid growing variety that lacked pigment, a characteristic of EMB with pathogenic potential. The EMB was finally traced to its source, the overhead water tank. Step (3) Remedial journey: By thorough cleaning of the water tank and enriching its chlorine content, the EMB was eliminated from its source. Step (4) Holding the gains: Protocol for cleaning the water tank once in 3 months was made. A checklist was prepared to ensure compliance to asepsis protocol in the operation theater. In the ensuing 5 years, the infection did not recur. RESULT: The bacteria that caused SSI were identified as EMB that grew in the water tank and contaminated the operation room. It could be eliminated by appropriate measures. INTERPRETATION: Water is a potential reservoir for EMB. Use of the term 'environmental mycobacteria' instead of 'atypical mycobacteria' will generate awareness about contamination as the cause of SSI. PMID- 26896271 TI - Mid-term outcomes of patients undergoing adjustable pulmonary artery banding. AB - OBJECTIVE: The adjustable pulmonary artery band (APAB) has been demonstrated by us earlier to be superior to the conventional pulmonary artery banding (CPAB), in terms of reduced early morbidity and mortality. In this study, we assessed the adequacy of the band and its complications over the mid-term. METHODS: Between 2002 and 2012, 73 patients underwent adjustable PAB, and their operative and follow-up data were collected and analyzed. RESULTS: There was one early death following the APAB. Follow-up data were available for 57 patients of which 44 patients (61.7%) underwent definitive repair, 10 were awaiting definitive repair, and 3 patients were kept on medical follow-up because of inadequate fall in pulmonary artery (PA) pressures. 14 patients (19%) were lost to follow-up. Major PA distortion or stenosis was absent in the majority. 1 patient had pseudoaneurysm of the main pulmonary artery (MPA) with sternal sinus infection and required surgical reconstruction. 1 patient had infective endocarditis of the pulmonary valve managed medically. Band migration was not encountered. There were two deaths after definitive repair and one after APAB. CONCLUSIONS: Patients undergoing APAB fulfilled the desired objectives of the pulmonary artery banding (PAB) with minimum PA complications in the mid-term. This added to the early postoperative benefits, makes the APAB an attractive alternative to the CPAB. PMID- 26896268 TI - Multimarker risk stratification approach and cardiovascular outcomes in patients with stable coronary artery disease undergoing elective percutaneous coronary intervention. AB - AIMS: We studied the utility of multimarker risk stratification approach to predict cardiovascular outcomes in patients with stable coronary artery disease, undergoing elective percutaneous coronary intervention (PCI). METHODS: We prospectively evaluated 302 consecutive patients with stable coronary artery disease and normal CPK-MB and cardiac troponin T levels, and who underwent elective PCI at our institution. The following cardiac biomarkers were measured before and between 12 and 24h post-procedure: CK-MB, cardiac troponin T, hs-CRP, and NT-ProBNP. Patients were followed up for a minimum of 6 months. RESULTS: Post PCI, CPK-MB levels were elevated but below myocardial infarction (MI) range in 70 patients (23%), and in the MI range in 6 patients (2%). Troponin T levels were detectable but below the 99th percentile (microleak) in 32 patients (10.6%) and elevated above the 99th percentile (periprocedural MI) in 104 patients (34.4%). At 9 months' follow-up, 1% died, 2% had stable angina, 10.3% had non-fatal MI, and 87.7% remained asymptomatic. There was no significant difference in clinical events among groups stratified by elevation of one biomarker or multiple biomarkers. CONCLUSION: Single or multiple biomarker strategy in patients with normal baseline biomarkers failed to predict major cardiac events after PCI over medium-term follow-up. PMID- 26896270 TI - A survey of cardiac implantable electronic device implantation in India: By Indian Society of Electrocardiology and Indian Heart Rhythm Society. AB - BACKGROUND: There is limited data regarding the demographics and type of cardiac implantable electronic device (CIED) in India. AIM: The aim of this survey was to define trends in CIED implants, which included permanent pacemakers (PM), intracardiac defibrillators (ICD), and cardiac resynchronization therapy pacemakers and defibrillators (CRT-P/D) devices in India. METHODS: The survey was the initiative of the Indian Society of Electrocardiology and the Indian Heart Rhythm Society. The type of CIED used, their indications, demographic characteristics, clinical status and co-morbidities were collected using a survey form over a period of 1 year. RESULTS: 2117 forms were analysed from 136 centers. PM for bradyarrhythmic indication constituted 80% of the devices implanted with ICD's and CRT-P/D forming approximately 10% each. The most common indication for PM implantation was complete atrio-ventricular block (76%). Single chamber (VVI) pacemakers formed 54% of implants, majority in males (64%). The indication for ICD implantation was almost equal for primary and secondary prevention. A single chamber ICD was most commonly implanted (65%). Coronary artery disease was the etiology in 58.5% of patients with ICD implants. CRT pacemakers were implanted mostly in patients with NYHA III/IV (82%), left ventricular ejection fraction <0.35 (88%) with CRT-P being most commonly used (57%). CONCLUSION: A large proportion of CIED implants in India are PM for bradyarrhythmic indications, predominantly AV block. ICD's are implanted almost equally for primary and secondary prophylaxis. Most CRT devices are implanted for NYHA Class III. There is a male predominance for implantation of CIED. PMID- 26896273 TI - Myocardial Performance Index (Tei Index): A simple tool to identify cardiac dysfunction in patients with diabetes mellitus. AB - BACKGROUND: Cardiac dysfunction is the major cause of morbidity and mortality in diabetes. Myocardial Performance Index (MPI/Tei Index) includes both systolic and diastolic time intervals to assess the global cardiac dysfunction. Our aim was to assess the MPI in patients with type 2 diabetes. MATERIAL AND METHODS: This hospital-based analytic observational study was performed in the tertiary care center. The conventional Doppler parameters, tissue Doppler-derived E/E' and MPI, were measured in all patients. RESULTS: 100 patients with type 2 diabetes were included in the study. 65 patients showed diastolic dysfunction, 33 with Grade I diastolic dysfunction, 23 with Grade II diastolic dysfunction, and 14 patients with Grade III diastolic dysfunction. The conventional Doppler showed abnormality in 44% of patients (33 patients with Grade I and 14 patient with Grade III). 23 patients were in Grade II diastolic dysfunction (12 patients showed reversal E/A on valsalva maneuver and 11 patients showed abnormality in tissue Doppler-derived E/E', E/E'>15). MPI with cut-off 0.36 was found to have 94% sensitivity, 100 specificity, and 94% PPV for the detection of cardiac dysfunction. MPI negatively correlated with systolic dysfunction (rho=0.455, p<0.001) and positively correlated with grade of diastolic dysfunction (rho=0.832, p<0.001) and NYHA grading of dyspnea (rho=0.872, p<0.001) CONCLUSIONS: MPI as a single parameter can be used for assessment in diabetic cardiac dysfunction. PMID- 26896272 TI - Endovascular reconstruction of popliteal and infrapopliteal arteries for limb salvage and wound healing in patients with critical limb ischemia - A retrospective analysis. AB - BACKGROUND: Advancement in endovascular techniques has led to rapid growth in endovascular revascularization, and it has emerged as a treatment for critical limb ischemia (CLI). Clinical effectiveness of revascularization has been frequently judged by vessel patency and limb salvage, but there is paucity of reports on outcomes of the wound. We present a retrospective analysis of immediate angiographic and 3-month clinical outcome of patients who underwent endovascular reconstruction of popliteal and infrapopliteal arteries for CLI. METHODS: All patients who underwent endovascular reconstruction of popliteal and/or infrapopliteal arteries for CLI and >70% stenosis on digital subtraction angiography between March 2010 and November 2014 and had a clinical follow-up of at least 3 months were selected for analysis. RESULTS: 34 patients underwent endovascular reconstruction. 9 patients (26%) underwent only POBA and remaining 25 (74%) underwent additional stenting. 13 patients (38%) had multiple segmental revascularization. 24 patients (71%) had successful vessel recanalization. Linear flow to foot in at least one artery could be achieved in 20 patients (59%) post revascularization. Successful wound healing occurred in 11 (35%) patients with an additional 7 (21%) patients showing clinical improvement in their wounds. Limb salvage was achieved in 33 patients (97%) at 3-month follow-up. CONCLUSION: Endovascular revascularization of popliteal and infrapopliteal arteries is a feasible, safe, and effective procedure for the treatment of CLI. Normal inflow and outflow with at least one of the three infrapopliteal vessels being patent is essential for adequate healing of chronic ulcers and prevention of major amputation. PMID- 26896274 TI - Rheumatic fever and rheumatic heart disease in Bangladesh: A review. AB - Rheumatic fever (RF) and rheumatic heart disease (RHD) are the most-common cardiovascular disease in young people aged <25 years, globally. They are important contributors to cardiovascular morbidity and mortality in Bangladesh. Classical risk factors, i.e. poverty, overcrowding, ignorance, and insufficient health care services were responsible for the high incidence and prevalence of these diseases over the last century. In concert with the progresses in socioeconomic indicators, advances in health sectors, improved public awareness, and antibiotic prophylaxis, acute RF came into control. However, chronic RHD continues to be prevalent, and the actual disease burden may be much higher. RHD predominantly affects the young adults, seriously incapacitates them, follows a protracted course, gets complicated because of delayed diagnosis and is sometimes maltreated. The treatment is often palliative and expensive. Large-scale epidemiological and clinical researches are needed to formulate evidence-based national policy to tackle this important public health issue in future. PMID- 26896275 TI - Transcatheter closure of post-myocardial infarction ventricular defect: Where are we? AB - Since 1988, TCC of PMIVSD became an alternative treatment for anatomically suitable patients with high risk of surgical closure. TCC is less invasive but the optimal timing and technique have not developed much in the last four decades. The dismal prognosis at the contemporary sight should not be discouraged. The rapid innovation in TAVI is an example. The learning curve slopes down to the line of inertia in inaction. Some innovations have slept for centuries but their potential needs to be celebrated. The published experience of TCC of PMIVSD across the globe is limited as they are based on consensus. The experience related to clinical practice has heterogeneous topography around the globe because of the morbid pathology. The increasing number of onsite cardiothoracic wings, better imaging tools, LVADS, and ECMO, along with improvement in well matching hardware to the pathology of PMIVSD, build incremental confidence. The improved outcomes believes in the enthusiasm of closing the PMIVSD using either surgical or TCC approach and is recommended. PMID- 26896276 TI - Abnormal origin of right coronary artery and use of Tiger catheter through femoral route. AB - BACKGROUND: Abnormal origin of right coronary artery (RCA) is not uncommon. The incidence is .25-.92%. Right Judkin catheter is used universally for engaging right coronary ostium from femoral route. We have tried Tiger catheter from femoral route in abnormal origin of RCA patients. We were successful in cannulating RCA ostium in most of the cases. MATERIALS AND METHODS: We have studied about 5120 patients over 4 years. We have selected patients from November 2010 to November 2014. Our patients are from two institutions-I.P.G.M.E.R., Kolkata and Burdwan Medical College, West Bengal. Right Judkin 3.5 and 4 were used universally. We have used AL-1,2,3, AR1,2, multipurpose, different guide catheters for cannulating RCA ostium in those cases where we failed to engage by right Judkin catheter. We have used Tiger catheter as a last resort when all endeavor failed. RESULTS AND ANALYSIS: Among 40 cases of left sinus origin Type A 9, Type B-14, Type C-6, Type D-3, and Type E-8 patients were observed. But 668 cases abnormal origin of RCA were from right coronary sinus only. High take-off origin were 422 cases (8%), low take-off were 132 cases (2.5%), and posterior origin were 114 cases (2%). We could engage right coronary ostium by Tiger catheter in 690 cases (97%). We failed in 23 cases (3%). CONCLUSION: Tiger catheter can be used successfully in abnormal RCA origin cases. It is more effective but less risky in comparison to other catheters. PMID- 26896277 TI - Life support training - Need of the hour in India. PMID- 26896278 TI - Application of 3D printing in medicine. PMID- 26896279 TI - A Three-Dimensional Organoid Culture System Derived from Human Glioblastomas Recapitulates the Hypoxic Gradients and Cancer Stem Cell Heterogeneity of Tumors Found In Vivo. AB - Many cancers feature cellular hierarchies that are driven by tumor-initiating cancer stem cells (CSC) and rely on complex interactions with the tumor microenvironment. Standard cell culture conditions fail to recapitulate the original tumor architecture or microenvironmental gradients and are not designed to retain the cellular heterogeneity of parental tumors. Here, we describe a three-dimensional culture system that supports the long-term growth and expansion of tumor organoids derived directly from glioblastoma specimens, including patient-derived primary cultures, xenografts, genetically engineered glioma models, or patient samples. Organoids derived from multiple regions of patient tumors retain selective tumorigenic potential. Furthermore, organoids could be established directly from brain metastases not typically amenable to in vitro culture. Once formed, tumor organoids grew for months and displayed regional heterogeneity with a rapidly dividing outer region of SOX2(+), OLIG2(+), and TLX(+) cells surrounding a hypoxic core of primarily non-stem senescent cells and diffuse, quiescent CSCs. Notably, non-stem cells within organoids were sensitive to radiotherapy, whereas adjacent CSCs were radioresistant. Orthotopic transplantation of patient-derived organoids resulted in tumors displaying histologic features, including single-cell invasiveness, that were more representative of the parental tumor compared with those formed from patient derived sphere cultures. In conclusion, we present a new ex vivo model in which phenotypically diverse stem and non-stem glioblastoma cell populations can be simultaneously cultured to explore new facets of microenvironmental influences and CSC biology. Cancer Res; 76(8); 2465-77. (c)2016 AACR. PMID- 26896280 TI - FGFR1 Induces Glioblastoma Radioresistance through the PLCgamma/Hif1alpha Pathway. AB - FGF2 signaling in glioblastoma induces resistance to radiotherapy, so targeting FGF2/FGFR pathways might offer a rational strategy for tumor radiosensitization. To investigate this possibility, we evaluated a specific role for FGFR1 in glioblastoma radioresistance as modeled by U87 and LN18 glioblastomas in mouse xenograft models. Silencing FGFR1 decreased radioresistance in a manner associated with radiation-induced centrosome overduplication and mitotic cell death. Inhibiting PLCgamma (PLCG1), a downstream effector signaling molecule for FGFR1, was sufficient to produce similar effects, arguing that PLCgamma is an essential mediator of FGFR1-induced radioresistance. FGFR1 silencing also reduced expression of HIF1alpha, which in addition to its roles in hypoxic responses exerts an independent effect on radioresistance. Finally, FGFR1 silencing delayed the growth of irradiated tumor xenografts, in a manner that was associated with reduced HIF1alpha levels but not blood vessel alterations. Taken together, our results offer a preclinical proof of concept that FGFR1 targeting can degrade radioresistance in glioblastoma, a widespread problem in this tumor, prompting clinical investigations of the use of FGFR1 inhibitors for radiosensitization. Cancer Res; 76(10); 3036-44. (c)2016 AACR. PMID- 26896282 TI - Is sciatic nerve block advantageous when combined with femoral nerve block for postoperative analgesia following total knee arthroplasty? a meta-analysis. AB - BACKGROUND: Total knee arthroplasty (TKA) is associated with moderate-to-severe postoperative pain despite the use of femoral nerve block (FNB). The analgesic benefits of adding sciatic nerve block (SNB) to FNB following TKA are unclear. The aim of this meta-analysis was to quantify the analgesic effects of adding SNB to FNB following TKA. METHODS: We searched the US National Library of Medicine (MEDLINE), Excerpta Medica (Embase), and Cochrane Central Controlled Trials Register databases in March 2015 for randomized and quasi-randomized controlled trials (RCTs) that evaluated the analgesic advantages of adding SNB to FNB compared to FNB alone after TKA. The designated primary outcome was intravenous morphine consumption during the 24-hr postoperative interval. The severity of pain was evaluated at rest and with movement two, four, eight, 12, 24, 36, and 48 hr postoperatively. Morphine consumption during the postoperative 24-48 hr interval, time to first analgesic request, opioid-related side effects, block related complications, patient satisfaction, functional recovery, and time to hospital discharge were also evaluated. Trials were stratified based on whether a single-shot SNB (SSNB) or continuous SNB (CSNB) was used. Data were combined using random effects modelling. RESULTS: Eight RCTs, including 379 patients, were analyzed. Five trials examined SSNB, and three assessed CSNB. Together, SSNB and CSNB reduced the 0-24 hr weighted mean difference [95% confidence interval] of morphine consumption by 10.6 [-20.9 to -0.3] mg (P = 0.042; I(2) = 97%) and 20.5 [-28.6 to -12.4] mg (P < 0.001, I(2) = 86%), respectively. SSNB reduced pain at rest and during movement up to 8 hr postoperatively (P = 0.023 and P < 0.001, respectively), whereas CSNB reduced pain at rest up to 36 hr (P = 0.004) and pain with movement up to 48 hr (P = 0.031). CSNB also decreased the odds of postoperative nausea and vomiting by 91% (P = 0.011). CONCLUSION: The available evidence supporting the analgesic benefits of adding SNB to FNB following TKA is marked by significant heterogeneity. With this challenge in mind, our meta analysis suggests that SNB can significantly reduce postoperative opioid consumption and diminish knee pain following TKA compared to no SNB in the setting of FNB. PMID- 26896281 TI - Bap1 Is a Bona Fide Tumor Suppressor: Genetic Evidence from Mouse Models Carrying Heterozygous Germline Bap1 Mutations. AB - Individuals harboring inherited heterozygous germline mutations in BAP1 are predisposed to a range of benign and malignant tumor types, including malignant mesothelioma, melanoma, and kidney carcinoma. However, evidence to support a tumor-suppressive role for BAP1 in cancer remains contradictory. To test experimentally whether BAP1 behaves as a tumor suppressor, we monitored spontaneous tumor development in three different mouse models with germline heterozygous mutations in Bap1, including two models in which the knock-in mutations are identical to those reported in human BAP1 cancer syndrome families. We observed spontaneous malignant tumors in 54 of 93 Bap1-mutant mice (58%) versus 4 of 43 (9%) wild-type littermates. All three Bap1-mutant models exhibited a high incidence and similar spectrum of neoplasms, including ovarian sex cord stromal tumors, lung and mammary carcinomas, and spindle cell tumors. Notably, we also observed malignant mesotheliomas in two Bap1-mutant mice, but not in any wild-type animals. We further confirmed that the remaining wild-type Bap1 allele was lost in both spontaneous ovarian tumors and mesotheliomas, resulting in the loss of Bap1 expression. Additional studies revealed that asbestos exposure induced a highly significant increase in the incidence of aggressive mesotheliomas in the two mouse models carrying clinically relevant Bap1 mutations compared with asbestos-exposed wild-type littermates. Collectively, these findings provide genetic evidence that Bap1 is a bona fide tumor suppressor gene and offer key insights into the contribution of carcinogen exposure to enhanced cancer susceptibility. Cancer Res; 76(9); 2836-44. (c)2016 AACR. PMID- 26896283 TI - CCM3/PDCD10 gene mutation in cerebral cavernous malformations associated with hyperkeratotic cutaneous capillary venous malformations. PMID- 26896284 TI - Interpreting change from patient reported outcome (PRO) endpoints: patient global ratings of concept versus patient global ratings of change, a case study among osteoporosis patients. AB - BACKGROUND: Regulatory guidance recommends anchor-based methods for interpretation of treatment effects measured by PRO endpoints. Methodological pros and cons of patient global ratings of change vs. patient global ratings of concept have been discussed but empirical evidence in support of either approach is lacking. This study evaluated the performance of patient global ratings of change and patient global ratings of concept for interpreting patient stability and patient improvement. METHODS: Patient global ratings of change and patient global ratings of concept were included in a psychometric validation study of an osteoporosis-targeted PRO instrument (the OPAQ-PF) to assess its ability to detect change and to derive responder definitions. 144 female osteoporosis patients with (n = 37) or without (n = 107) a recent (within 6 weeks) fragility fracture completed the OPAQ-PF and global items at baseline, 2 weeks (no recent fracture), and 12 weeks (recent fracture) post-baseline. RESULTS: Results differed between the two methods. Recent fracture patients reported more improvement while patients without recent fracture reported more stability on ratings of change than ratings of concept. However, correlations with OPAQ-PF score change were stronger for ratings of concept than ratings of change (both groups). Effect sizes for OPAQ-PF score change increased consistently with level of change in ratings of concept but inconsistently with ratings of change, with the mean AUC for prediction of a one-point change being 0.72 vs. 0.56. CONCLUSIONS: This study provides initial empirical support for methodological and regulatory recommendations to use patient global ratings of concept rather than ratings of change when interpreting change captured by PRO instruments in studies evaluating treatment effects. These findings warrant being confirmed in a purpose designed larger scale analysis. PMID- 26896285 TI - Nasopharyngeal carriage of Streptococcus pneumoniae in adults infected with human immunodeficiency virus in Jakarta, Indonesia. AB - This study investigated the distribution of serotype and antimicrobial susceptibility of Streptococcus pneumoniae carried by adults infected with human immunodeficiency virus (HIV) in Jakarta, Indonesia. Specimens of nasopharyngeal swab were collected from 200 HIV infected adults aged 21 to 63 years. Identification of S. pneumoniae was done by optochin susceptibility test and PCR for the presence of psaA and lytA genes. Serotyping was performed with sequential multiplex PCR and antibiotic susceptibility with the disk diffusion method. S. pneumoniae strains were carried by 10% adults with serotype 6A/B 20% was common serotype among cultured strains in 20 adults. Most of isolates were susceptible to chloramphenicol (80%) followed by clindamycin (75%), erythromycin (75%), penicillin (55%), and tetracycline (50%). This study found resistance to sulphamethoxazole/trimethoprim was most common with only 15% of strains being susceptible. High non-susceptibility to sulphamethoxazole/trimethoprim was observed in S. pneumoniae strains carried by HIV infected adults in Jakarta, Indonesia. PMID- 26896287 TI - Identification and Treatment of Human Trafficking Victims in the Emergency Department: A Case Report. AB - BACKGROUND: Human trafficking victims experience extreme exploitation and have unique health needs, yet too often go undetected by physicians and providers in the Emergency Department (ED). We report a clinical case of human trafficking of a white, English-speaking United States citizen and discuss the features of presentation and treatment options for human trafficking victims upon presentation to the ED. CASE REPORT: A 29-year-old woman with a past medical history significant for intravenous drug abuse and recent relapse presented to the ED after a reported sexual assault. The patient was discharged that evening and returned to the ED the following day acutely suicidal. The patient divulged that she had been kidnapped and raped at gunpoint by numerous individuals as a result of a debt owed to her drug dealers. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Many human trafficking victims present to an ED during the course of their exploitation. To that end, EDs provide one of a limited set of opportunities to intervene in the human trafficking cycle of exploitation, and physicians as well as other ED staff should be equipped to respond. PMID- 26896286 TI - Bio-absorbable antibiotic impregnated beads for the treatment of prosthetic vascular graft infections. AB - OBJECTIVE: There is limited investigation into the use of bio-absorbable antibiotic beads for the treatment of prosthetic vascular graft infections. Our goal was to investigate the rates of infection eradication, graft preservation, and limb salvage in patients who are not candidates for graft explant or extensive reconstruction. METHODS: A retrospective review of patients implanted with antibiotic impregnated bio-absorbable calcium sulfate beads at a major university center was conducted. RESULTS: Six patients with prosthetic graft infections were treated with bio-absorbable antibiotics beads from 2012-2014. Grafts included an aortobifemoral, an aorto-hepatic/superior mesenteric artery, and four extra-anatomic bypasses. Pathogens included Gram-positive and Gram negative bacteria. Half of the patients underwent graft explant with reconstruction and half debridement of the original graft, all with antibiotic bead placement around the graft. Mean follow-up was 7.3 +/- 8.3 months; all patients had infection resolution, healed wounds, and 100% graft patency, limb salvage, and survival. CONCLUSION: This report details the successful use of bio absorbable antibiotic beads for the treatment prosthetic vascular graft infections in patients at high risk for graft explant or major vascular reconstruction. At early follow-up, we demonstrate successful infection suppression, graft preservation, and limb salvage with the use of these beads in a subset of vascular patients. PMID- 26896288 TI - Hypercortisolism Manifesting as Severe Weight Loss, Hypokalemia, and Hyperglycemia in the Emergency Department. AB - BACKGROUND: The concurrence of ectopic adrenocorticotropic hormone (ACTH) syndrome (ectopic Cushing syndrome) and cancer is uncommon in the emergency department (ED) setting, but a constellation of nonspecific signs and symptoms can suggest the presence of Cushing syndrome. CASE REPORT: A 65-year-old woman with diabetes visited the ED complaining of severe weight loss, generalized weakness, and hypokalemia. She was treated for hypokalemia and thrush. She was found to have a lung mass with a large pleural effusion. Upon discovery of the suspected malignancy, the patient was referred to the ED of a comprehensive cancer center, where she was diagnosed with ectopic Cushing syndrome and admitted to the hospital for further evaluation and treatment. WHY SHOULD THE EMERGENCY PHYSICIAN BE AWARE OF THIS?: The emergency physician should be able to recognize Cushing syndrome in cancer patients so that the paraneoplastic syndrome can be managed to avoid complications during cancer treatment. PMID- 26896289 TI - Using the Physical Examination to Diagnose Patients with Acute Dizziness and Vertigo. AB - BACKGROUND: Emergency department (ED) patients who present with acute dizziness or vertigo can be challenging to diagnose. Roughly half have general medical disorders that are usually apparent from the context, associated symptoms, or initial laboratory tests. The rest include a mix of common inner ear disorders and uncommon neurologic ones, particularly vertebrobasilar strokes or posterior fossa mass lesions. In these latter cases, misdiagnosis can lead to serious adverse consequences for patients. OBJECTIVE: Our aim was to assist emergency physicians to use the physical examination effectively to make a specific diagnosis in patients with acute dizziness or vertigo. DISCUSSION: Recent evidence indicates that the physical examination can help physicians accurately discriminate between benign inner ear conditions and dangerous central ones, enabling correct management of peripheral vestibular disease and avoiding dangerous misdiagnoses of central ones. Patients with the acute vestibular syndrome mostly have vestibular neuritis, but some have stroke. Data suggest that focused eye movement examinations, at least when performed by specialists, are more sensitive for detecting early stroke than brain imaging, including diffusion weighted magnetic resonance imaging. Patients with the triggered episodic vestibular syndrome mostly have benign paroxysmal positional vertigo (BPPV), but some have posterior fossa mass lesions. Specific positional tests to provoke nystagmus can confirm a BPPV diagnosis at the bedside, enabling immediate curative therapy, or indicate the need for imaging. CONCLUSIONS: Emergency physicians can effectively use the physical examination to make a specific diagnosis in patients with acute dizziness or vertigo. They must understand the limitations of brain imaging. This may reduce misdiagnosis of serious central causes of dizziness, including posterior circulation stroke and posterior fossa mass lesions, and improve resource utilization. PMID- 26896290 TI - Use of CDC Vaccine Schedules Smartphone Application to Prescribe Vaccines for HIV Infected Adults. PMID- 26896291 TI - Probiotic Lactobacillus casei strain Shirota relieves stress-associated symptoms by modulating the gut-brain interaction in human and animal models. AB - BACKGROUND: This study aimed to examine the effects of Lactobacillus casei strain Shirota (LcS) on gut-brain interactions under stressful conditions. METHODS: Three double-blind, placebo-controlled trials were conducted to examine the effects of LcS on psychological and physiological stress responses in healthy medical students under academic examination stress. Subjects received LcS fermented milk or placebo daily for 8 weeks prior to taking a national standardized examination. Subjective anxiety scores, salivary cortisol levels, and the presence of physical symptoms during the intervention were pooled and analyzed. In the animal study, rats were given feed with or without LcS for 2 weeks, then submitted to water avoidance stress (WAS). Plasma corticosterone concentration and the expression of cFos and corticotropin releasing factor (CRF) in the paraventricular nucleus (PVN) were measured immediately after WAS. In an electrophysiological study, gastric vagal afferent nerve activity was monitored after intragastric administration of LcS to urethane-anesthetized rats. KEY RESULTS: Academic stress-induced increases in salivary cortisol levels and the incidence rate of physical symptoms were significantly suppressed in the LcS group compared with the placebo group. In rats pretreated with LcS, WAS-induced increases in plasma corticosterone were significantly suppressed, and the number of CRF-expressing cells in the PVN was reduced. Intragastric administration of LcS stimulated gastric vagal afferent activity in a dose-dependent manner. CONCLUSIONS & INFERENCES: These findings suggest that LcS may prevent hypersecretion of cortisol and physical symptoms under stressful conditions, possibly through vagal afferent signaling to the brain and reduced stress reactivity in the PVN. PMID- 26896292 TI - Effects of beta-hydroxy-beta-methyl butyrate on working memory and cognitive flexibility in an animal model of aging. AB - OBJECTIVES: Normal aging results in cognitive decline and nutritional interventions have been suggested as potential approaches for mitigating these deficits. Here, we used rats to investigate the effects of short- and long-term dietary supplementation with the leucine metabolite beta-hydroxy-beta-methyl butyrate (HMB) on working memory and cognitive flexibility. METHODS: Beginning ~12 months of age, male and female Long-Evans rats were given twice daily access to sipper tubes containing calcium HMB (450 mg/kg) or vehicle (285 mg/kg calcium lactate) in a sucrose solution (20% w/v). Supplementation continued for 1 or 7 months (middle- and old-age (OA) groups, respectively) before testing began. Working memory was assessed by requiring rats to respond on a previously sampled lever following various delays. Cognitive flexibility was assessed by training rats to earn food according to a visual strategy and then, once acquired, shifting to an egocentric response strategy. RESULTS: Treatment with HMB improved working memory performance in middle-age (MA) males and OA rats of both sexes. In the cognitive flexibility task, there was a significant age-dependent deficit in acquisition of the visual strategy that was not apparent in OA males treated with HMB. Furthermore, HMB ameliorated an apparent deficit in visual strategy acquisition in MA females. DISCUSSION: Together, these findings suggest that daily nutritional supplementation with HMB facilitates learning and improves working memory performance. As such, HMB supplementation may mitigate age-related cognitive deficits and may therefore be an effective tool to combat this undesirable feature of the aging process. PMID- 26896293 TI - Immunologic prediction of relapse in patients with pemphigus vulgaris (PV) in clinical remission. AB - BACKGROUND: Pemphigus vulgaris (PV) is characterized by multiple relapses, occurring especially in patients on minimal therapy or off therapy. OBJECTIVE: To identify immunologic predictors (anti-desmoglein [Dsg] 1 and 3 antibodies; direct immunofluorescence [DIF]) for relapse in PV patients. METHODS: Eighty-nine patients in complete clinical remission for at least 6 months and receiving less than or equal to 10 mg prednisolone daily and no immunosuppressive drugs were evaluated using DIF (n=89) and Dsg ELISA (n=46). They were followed until relapse or for at least 18 months. RESULTS: DIF was positive in 44 of 89 patients (49.5%); anti-Dsg 3 antibodies were detected in 18 of 46 patients (39.1%) and anti-Dsg 1 antibodies were detected in 4 of 46 patients (8.7%). Relapse occurred in 38 patients (42.7%). Mean relapse-free time was significantly shorter in anti Dsg 3-positive patients compared to anti-Dsg 3- negative patients (P = .015) and in DIF-positive patients compared to DIF-negative patients (P = .047), but not in anti-Dsg 1- positive patients compared to anti-Dsg 1-negative patients (P = .501). Sensitivity and predictive values of neither of these tests were high. LIMITATIONS: Small number of anti-Dsg 1-positive patients and use of conventional ELISA. CONCLUSION: Positive anti-Dsg 3 ELISA and, to a lesser degree, positive DIF are predictors of relapse in PV patients in clinical remission. Decision on discontinuing treatment should be based on the results of these tests as well as on clinical findings. PMID- 26896295 TI - Emergency department utilization of pediatric dermatology (PD) consultations. AB - BACKGROUND: There are few published data about pediatric dermatology (PD) consultations in the pediatric emergency department (PED). OBJECTIVE: We profiled PD consultations to determine patterns of dermatology utilization by the PED. METHODS: We reviewed electronic medical records of 347 PD consultations from the PED over a 36-month period from January 2011 to December 2013. We recorded patient age and gender; PED diagnosis; PD diagnosis; skin biopsy, if needed, with histopathology report; and outpatient PD follow-up. RESULTS: Patient age ranged from 3 days to 18 years with the majority (54.8%) of consultations for patients aged 0 days to 5 years. The most common diagnostic categories were infections and inflammatory skin disorders. Atopic dermatitis was the most common individual diagnosis. In all, 48.1% of patients had PD outpatient clinic follow-up. The rate of diagnostic agreement between the pediatric emergency medicine and PD provider was 58%. LIMITATIONS: Use of electronic medical records, retrospective study design, and population based at a tertiary-care children's hospital represent potential limitations. CONCLUSIONS: PD providers contribute to patient care in the PED. Dermatology education in the PED should include the more commonly encountered disorders identified in this study, including infectious diseases and atopic dermatitis. PMID- 26896296 TI - Receptor tyrosine kinase KIT: Prognostic and therapeutic involvement in canine mast cell tumours. PMID- 26896297 TI - Enoxaparin has no significant anticoagulation activity in healthy Beagles at a dose of 0.8 mg/kg four times daily. AB - Enoxaparin at 0.8 mg/kg every 6 h is used in dogs to prevent prothrombotic events, but has only been validated in healthy Greyhounds, a breed with documented hypocoagulable haemostatic profiles in vitro and bleeding tendencies in vivo. This study investigated the effects of enoxaparin at this dose rate on the coagulation parameters of eight healthy adult Beagles over a 48 h period. Anti-Xa activity was significantly increased 3 h after the second and third of nine injections, and target anti-Xa activity was only reached transiently in 3/8 dogs. Paradoxically, a transient increase in endogenous thrombin potential was observed 6 h after the third injection. Other haematologic, biochemical and coagulation parameters were not significantly altered from the baseline values during enoxaparin treatment (P > 0.05). This study suggests that assumptions regarding the pharmacodynamic effects of enoxaparin are not generalisable across breeds. PMID- 26896294 TI - Standardization of terminology in dermoscopy/dermatoscopy: Results of the third consensus conference of the International Society of Dermoscopy. AB - BACKGROUND: Evolving dermoscopic terminology motivated us to initiate a new consensus. OBJECTIVE: We sought to establish a dictionary of standardized terms. METHODS: We reviewed the medical literature, conducted a survey, and convened a discussion among experts. RESULTS: Two competitive terminologies exist, a more metaphoric terminology that includes numerous terms and a descriptive terminology based on 5 basic terms. In a survey among members of the International Society of Dermoscopy (IDS) 23.5% (n = 201) participants preferentially use descriptive terminology, 20.1% (n = 172) use metaphoric terminology, and 484 (56.5%) use both. More participants who had been initially trained by metaphoric terminology prefer using descriptive terminology than vice versa (9.7% vs 2.6%, P < .001). Most new terms that were published since the last consensus conference in 2003 were unknown to the majority of the participants. There was uniform consensus that both terminologies are suitable, that metaphoric terms need definitions, that synonyms should be avoided, and that the creation of new metaphoric terms should be discouraged. The expert panel proposed a dictionary of standardized terms taking account of metaphoric and descriptive terms. LIMITATIONS: A consensus seeks a workable compromise but does not guarantee its implementation. CONCLUSION: The new consensus provides a revised framework of standardized terms to enhance the consistent use of dermoscopic terminology. PMID- 26896298 TI - Development of a nomogram combining clinical staging with (18)F-FDG PET/CT image features in non-small-cell lung cancer stage I-III. AB - PURPOSE: Our goal was to develop a nomogram by exploiting intratumour heterogeneity on CT and PET images from routine (18)F-FDG PET/CT acquisitions to identify patients with the poorest prognosis. METHODS: This retrospective study included 116 patients with NSCLC stage I, II or III and with staging (18)F-FDG PET/CT imaging. Primary tumour volumes were delineated using the FLAB algorithm and 3D SlicerTM on PET and CT images, respectively. PET and CT heterogeneities were quantified using texture analysis. The reproducibility of the CT features was assessed on a separate test-retest dataset. The stratification power of the PET/CT features was evaluated using the Kaplan-Meier method and the log-rank test. The best standard metric (functional volume) was combined with the least redundant and most prognostic PET/CT heterogeneity features to build the nomogram. RESULTS: PET entropy and CT zone percentage had the highest complementary values with clinical stage and functional volume. The nomogram improved stratification amongst patients with stage II and III disease, allowing identification of patients with the poorest prognosis (clinical stage III, large tumour volume, high PET heterogeneity and low CT heterogeneity). CONCLUSION: Intratumour heterogeneity quantified using textural features on both CT and PET images from routine staging (18)F-FDG PET/CT acquisitions can be used to create a nomogram with higher stratification power than staging alone. PMID- 26896299 TI - Structural studies reveal an important role for the pleiotrophin C-terminus in mediating interactions with chondroitin sulfate. AB - Pleiotrophin (PTN) is a potent glycosaminoglycan-binding cytokine that is important in neural development, angiogenesis and tissue regeneration. Much of its activity is attributed to its interactions with the chondroitin sulfate (CS) proteoglycan, receptor type protein tyrosine phosphatase zeta (PTPRZ). However, there is little high resolution structural information on the interactions between PTN and CS, nor is it clear why the C-terminal tail of PTN is necessary for signaling through PTPRZ, even though it does not contribute to heparin binding. We determined the first structure of PTN and analyzed its interactions with CS. Our structure shows that PTN possesses large basic surfaces on both of its structured domains and also that residues in the hinge segment connecting the domains have significant contacts with the C-terminal domain. Our analysis of PTN CS interactions showed that the C-terminal tail of PTN is essential for maintaining stable interactions with chondroitin sulfate A, the type of CS commonly found on PTPRZ. These results offer the first possible explanation of why truncated PTN missing the C-terminal tail is unable to signal through PTPRZ. NMR analysis of the interactions of PTN with CS revealed that the C-terminal domain and hinge of PTN make up the major CS-binding site in PTN, and that removal of the C-terminal tail weakened the affinity of the site for CSA but not for other high sulfation density CS. DATABASE: Coordinates of the ensemble of ten PTN structures have been deposited in RCSB under accession number 2n6f. Chemical shifts assignments and structural constraints have been deposited in BMRB under accession number 25762. PMID- 26896300 TI - Exploring stop-go decision zones at rural high-speed intersections with flashing green signal and insufficient yellow time in China. AB - The objective of this study is to empirically analyze and model the stop-go decision behavior of drivers at rural high-speed intersections in China, where a flashing green signal of 3s followed by a yellow signal of 3s is commonly applied to end a green phase. 1, 186 high-resolution vehicle trajectories were collected at four typical high-speed intersection approaches in Shanghai and used for the identification of actual stop-go decision zones and the modeling of stop-go decision behavior. Results indicate that the presence of flashing green significantly changed the theoretical decision zones based on the conventional Dilemma Zone theory. The actual stop-go decision zones at the study intersections were thus formulated and identified based on the empirical data. Binary Logistic model and Fuzzy Logic model were then developed to further explore the impacts of flashing green on the stop-go behavior of drivers. It was found that the Fuzzy Logic model could produce comparably good estimation results as compared to the traditional Binary Logistic models. The findings of this study could contribute the development of effective dilemma zone protection strategies, the improvement of stop-go decision model embedded in the microscopic traffic simulation software and the proper design of signal change and clearance intervals at high-speed intersections in China. PMID- 26896302 TI - Pharmacokinetics and pharmacodynamics of oral acetaminophen in combination with codeine in healthy Greyhound dogs. AB - The purpose of this study was to determine the pharmacokinetic and antinociceptive effects of an acetaminophen/codeine combination administered orally to six healthy greyhounds. Antinociception was assessed using an electronic von Frey (vF) device as a mechanical/pressure model. Acetaminophen was administered at a dose of 600 mg (14.4-23.1 mg/kg) and codeine phosphate at 90 mg (2.1-3.3 mg/kg) equivalent to 67.5 mg codeine base (1.6-2.5 mg/kg). The geometric mean maximum plasma concentrations of acetaminophen, codeine, and codeine-6 glucuronide were 7.95 MUg/mL, 11.0 ng/mL, and 3819 ng/mL, respectively. Morphine concentrations were <1 ng/mL. The terminal half-lives of acetaminophen, codeine, and codeine-6-glucuronide were 0.94, 1.71, and 3.12 h. There were no significant changes in vF thresholds, except at 12 h which decreased on average by 17% compared to baseline. The decrease in vF thresholds at 12 h could be due to aversion, hyperalgesia, or random variability. The lack of antinociception in this study could be due to a true lack of antinociception, lack of model sensitivity, or specificity. Further studies using different models (including clinical trials), different dog breeds, multiple dose regimens, and a range of dosages are needed prior to recommended use or concluding lack of efficacy for oral acetaminophen/codeine in dogs. PMID- 26896301 TI - Bean pod mottle virus: a new powerful tool for functional genomics studies in Pisum sativum. AB - Pea (Pisum sativum L.) is an important legume worldwide. The importance of pea in arable rotations and nutritional value for both human and animal consumption have fostered sustained production and different studies to improve agronomic traits of interest. Moreover, complete sequencing of the pea genome is currently underway and will lead to the identification of a large number of genes potentially associated with important agronomic traits. Because stable genetic transformation is laborious for pea, virus-induced gene silencing (VIGS) appears as a powerful alternative technology for determining the function of unknown genes. In this work, we present a rapid and efficient viral inoculation method using DNA infectious plasmids of Bean pod mottle virus (BPMV)-derived VIGS vector. Six pea genotypes with important genes controlling biotic and/or abiotic stresses were found susceptible to BPMV carrying a GFP reporter gene and showed fluorescence in both shoots and roots. In a second step, we investigated 37 additional pea genotypes and found that 30 were susceptible to BPMV and only 7 were resistant. The capacity of BPMV to induce silencing of endogenes was investigated in the most susceptible genotype using two visual reporter genes: PsPDS and PsKORRIGAN1 (PsKOR1) encoding PHYTOENE DESATURASE and a 1,4-beta-D glucanase, respectively. The features of the 'one-step' BPMV-derived VIGS vector include (i) the ease of rub-inoculation, without any need for biolistic or agro inoculation procedures, (ii) simple cost-effective procedure and (iii) noninterference of viral symptoms with silencing. These features make BPMV the most adapted VIGS vector in pea to make low- to high-throughput VIGS studies. PMID- 26896304 TI - Is bilateral thoracocentesis necessary in bilateral pleural effusion? PMID- 26896303 TI - Propensity score-matched study of laparoscopic and open surgery for colorectal cancer in rural hospitals. AB - BACKGROUND AND AIM: Various randomized clinical studies have suggested that short and long-term outcomes of laparoscopic surgery (LAP) for colorectal cancer are comparable with those of open surgery (OP). However, these studies were performed in high-volume hospitals. The aim of the present study was to compare the outcomes of LAP versus OP for colorectal cancer in rural hospitals. METHODS: This was a multicenter retrospective propensity score-matched case-control study of patients who underwent colorectal surgery from January 2004 to April 2009 in 10 hospitals in Japan. All patients underwent curative surgery for pathologically diagnosed stage II or III colorectal cancer. The primary end point was 5-year overall survival (OS). The secondary end points were disease-free survival (DFS) and postoperative complications. RESULTS: In total, 319 patients who underwent LAP and 1020 patients who underwent OP were balanced to 261 pairs. There was no significant difference in the OS and DFS between two groups. The operation time was significantly shorter for OP than for LAP. Blood loss was significantly lower in LAP than in OP. There was no difference in intraoperative morbidity between the two groups. The postoperative morbidity was significantly lower in LAP than in OP. The hospital stay was significantly shorter in LAP than in OP. There was no significant difference in 90-day postoperative mortality. CONCLUSIONS: Laparoscopic surgery may be a feasible option for colorectal cancer in rural hospitals. PMID- 26896306 TI - Paradoxical nocturnal elevation of sympathetic tone and spontaneous ventricular fibrillation in Brugada syndrome. AB - BACKGROUND: Nocturnal dominance of the incidence of spontaneous ventricular tachyarrhythmias has been reported in patients with Brugada syndrome (BrS). The purpose of the present study is to analyze the QT dynamics and autonomic balance as well as their diurnal variations in BrS patients. METHODS: Of the 33 consecutive patients with BrS included in the study, 14 had a history of cardiopulmonary arrest due to spontaneous ventricular fibrillation (VF) episodes (VF-BrS) and 19 had asymptomatic BrS (A-BrS). QT dynamics and heart rate variability were analyzed using 24-h Holter electrocardiogram recordings. RESULTS: Of the total 14 first cardiopulmonary arrest episodes due to spontaneous VF, 11 (79%) occurred in VF-BrS patients during the nighttime or at rest. The QT/RR slope during daytime was significantly steeper than that during nighttime in the A-BrS patients (p=0.031), but not in the VF-BrS patients (p=1.0). There were significant diurnal differences pertaining to the high-frequency (HF) and low-frequency (LF)/HF ratios in the A-BrS patients (p=0.019 and p=0.019, respectively), but not in the VF-BrS patients (p=1.0 and p=1.0, respectively). The VF-BrS patients were characterized by relatively high LF/HF ratios, whereas the A-BrS patients were characterized by relatively low LF/HF ratios throughout the daytime and nighttime. Furthermore, the LF/HF ratios during the nighttime in the VF-BrS patients were significantly higher than those in the A-BrS patients (p=0.021). CONCLUSIONS: Most first episodes of spontaneous VF in the VF-BrS patients occurred during the nighttime or at rest. The autonomic imbalance of paradoxical nocturnal elevation of the sympathetic tone along with an underlying persistent sympathetic tone throughout the day may play a key role for spontaneous VF initiation in BrS patients. PMID- 26896305 TI - Motivation for Different Types and Doses of Exercise During Breast Cancer Chemotherapy: a Randomized Controlled Trial. AB - BACKGROUND: Exercise is beneficial for breast cancer patients during chemotherapy, but their motivation to perform different types and doses of exercise is unknown. PURPOSE: The purpose of this study was to examine the anticipated and experienced motivation of breast cancer patients before and after three different exercise programs during chemotherapy. METHODS: Breast cancer patients initiating chemotherapy (N = 301) were randomized to a standard dose of 25-30 min of aerobic exercise, a higher dose of 50-60 min of aerobic exercise, or a combined dose of 50-60 min of aerobic and resistance exercise. Patient preference and motivational outcomes from the theory of planned behavior (i.e., perceived benefit, enjoyment, support, difficulty, and motivation) were assessed before and after the interventions. RESULTS: At pre-randomization, breast cancer patients were significantly (p < 0.001) more likely to prefer the combined program (80.1 %); however, after the interventions there was a significant (p < 0.001) increase in the number of patients preferring the high volume program and having no preference. At pre-randomization, breast cancer patients anticipated more favorable motivational outcomes for the combined program and less favorable motivational outcomes for the high volume program (all p < 0.001). After the interventions, the motivational outcomes experienced exceeded the anticipated motivational outcomes significantly more in the high volume group than the standard or combined groups. CONCLUSIONS: Anticipated motivational outcomes for different types and doses of exercise during chemotherapy varied considerably at pre-randomization, but the motivational outcomes experienced after the three interventions were similar. Clinicians can recommend any of the three exercise interventions to breast cancer patients knowing that positive motivational outcomes will result. Clinicaltrials.gov identifier: NCT00249015 . PMID- 26896307 TI - Aortic annulus displacement assessed by contrast left ventriculography during invasive coronary angiography as a predictor of adverse events. AB - BACKGROUND: We propose the use of aortic annulus displacement (AAD) detected on contrast left ventriculography (LVG) during invasive coronary angiography as a marker of left ventricular (LV) long-axis shortening. In the present study, we aimed to investigate whether AAD is associated with adverse events in patients who underwent coronary angiography because of suspected coronary artery disease. METHODS: In this retrospective study, we evaluated the medical records of 998 consecutive patients who underwent invasive coronary angiography and LVG. LV lengths were measured from the apex to the aortic valve insertion by using LVG images. AAD (%) was calculated as [(LV end-diastolic length-LV end-systolic length)/LV end-diastolic length]*100. RESULTS: The participants' median age was 67 years. Ninety-six adverse events (composite events; all-cause death, 39; congestive heart failure, 21; late revascularization, 34; and myocardial infarction, 2) were observed during a median follow-up period of 3.1 years. In multivariate Cox regression analysis, adverse events were associated with lower AAD (hazard ratio, 0.703; p=0.002), after adjusting for traditional risk factors and coronary artery stenosis. The area under the curve of AAD for predicting adverse events was greater than that of LV ejection fraction (0.656 vs. 0.541, p<0.05). CONCLUSIONS: AAD was superior to LV ejection fraction as a predictor of adverse events in patients with and without coronary arterial stenosis. AAD may be the optimal method for assessing longitudinal LV systolic function in the catheter laboratory. PMID- 26896309 TI - The prevalence of pressure ulcers in the paediatric population. AB - BACKGROUND: A paucity of research related to the problem of pressure ulcers in paediatrics is found, with a variety of reported prevalence rates. OBJECTIVE: To record the prevalence, location and categories of PU in the inpatient paediatric wards, and to identify the characteristics of pressure ulcer patients. DESIGN: A descriptive point prevalence study. SETTING: All paediatric inpatient wards in two hospitals in Jordan. One of which is a university-affiliated hospital and the other a paediatric public hospital. Isolation, burn and emergency units, outpatients' clinics and psychiatric wards were excluded. SAMPLE: One sixty six paediatric patients aged from one day up to 18 years from both hospitals. METHODS: Patients who met the inclusion criteria were included and examined for the existence of pressure ulcers on one day in each hospital by the primary investigator. The European Pressure Ulcer Advisory Panel classification system was used to categorise each identified ulcer. The characteristics of ulcers were collected as well. RESULTS: Sixteen ulcers were identified in 11 patients, giving a prevalence rate of 6.6%.When Category I ulcers were excluded, the prevalence rate dropped to 2.4%. All except one of the PU patients were being treated in critical care units (n = 10, 90.9%), and most of the ulcers were category one (n = 7, 63.6%) and caused by devices (n = 7, 63.6). The face was the most frequently reported location of PUs (n = 6, 54.5%), followed by the occiput (n = 2, 18.2%). Most PU patients were male (n = 6, 54.5%), and less than 12 months old (n = 8, 72.7%). PU patients had experienced longer hospital stays than patients free from PU (U = 499.0, p = 0.02). CONCLUSION: Jordanian paediatric patients do have pressure ulcers, with a prevalence rate congruent with previously reported international rates. Most of the ulcers found were caused by devices used in critical care units. This should encourage nurses to pay extra attention to their paediatric patients when they are connected to medical devices. PMID- 26896308 TI - MicroRNA-9 regulates cardiac fibrosis by targeting PDGFR-beta in rats. AB - The proliferation of cardiac fibroblasts (CFs) and excessive deposition of extracellular matrix (ECM) are the main pathological characteristics of cardiac fibrosis. In recent years, microRNAs (miRNAs) have been found to be a new kind of regulator in cardiac fibrosis. The purpose of this study was to investigate the role of microRNA-9 (miR-9) in the process of cardiac fibrosis and its mechanism. Treatment of cultured neonatal rat CFs with PDGF-BB or serum suppressed the expression of miR-9. Overexpression of miR-9 obviously inhibited neonatal rat CFs proliferation and collagen production as detected by MTT assays, qRT-PCR, and western blotting. The effects of miR-9 in CFs were abrogated by co-transfection with miR-9 inhibitors. Overexpression of miR-9 reduced the mRNA and protein levels of PDGFR-betaand its downstream protein, extracellular signal-regulated kinase (ERK) 1/2. Silencing PDGFR-betaby small interfering RNA mimicked the anti fibrotic action of miR-9, whereas overexpression of PGDFR-beta canceled the effect of miR-9 in cultured CFs. Dual-luciferase reporter assays showed that PDGFR-betawas a direct target of miR-9. Overexpression of miR-9 inhibited cardiac fibrosis by targeting PDGFR-beta, indicating that miR-9 might play a role in the treatment of cardiac fibrosis. PMID- 26896311 TI - Discovery of active components in herbs using chromatographic separation coupled with online bioassay. AB - Discovery of bioactive compounds from complex mixtures is a challenge. In past decades, several strategies were developed and implemented for rapid and effective screening and characterization of bioactive components in complex matrices. This review mainly focused on the online strategies, which integrated the separation science, mass spectrometry, and bioactivity screening in a single platform, allowing simultaneous screening and characterization of active compounds from complex matrices, especially from the herbs. The online screening methodologies, including pre-column affinity-based screening and post-column bioassay, were discussed and their applied examples were also presented to illustrate the strengths and limitations of these approaches. PMID- 26896310 TI - Immediate stabilization of human blood for delayed quantification of endogenous thiols and disulfides. AB - Endogenous thiols undergo rapid and reversible oxidation to disulfides when exposed to oxidants and are, therefore, suitable biomarkers of oxidative stress. However, accurate analysis of thiols in blood is frequently compromised by their artifactual oxidation during sample manipulation, which spuriously elevates the disulfide levels. Here, we describe a validated pre-analytical procedure that prevents both artifactual oxidation of thiols during sample manipulation and their oxidative decay for months in biosamples that are stored at -80 degrees C. Addition of N-ethylmaleimide to blood samples from healthy donors was used to stabilize whole blood, red blood cells, platelets and plasma disulfides, whereas addition of citrate buffer followed by dilution of plasma with H2O was used to stabilize plasma thiols. The concentrations of thiols and disulfides were stable in all biosamples for at least 6 months when analyzed by UV/Vis HPLC at regular intervals. Only 3 ml of blood were needed to perform the analyses of thiols and disulfides in the different blood fractions. This pre-analytical procedure is reliable for use in both animal and human prospective studies. Its ease of implementation makes the method suitable for application to multicenter studies where blood samples are collected by different sites and personnel and are shipped to specific specialized laboratories. PMID- 26896312 TI - An ultra-high pressure liquid chromatography-tandem mass spectrometry method for the quantification of teicoplanin in plasma of neonates. AB - The development and validation of an ultra-high pressure liquid chromatography (UHPLC) tandem mass spectrometry (MS/MS) method was performed with the aim to be applied for the quantification of plasma teicoplanin concentrations in neonates. Pharmacokinetic data of teicoplanin in the neonatal population is very limited, therefore, a sensitive and reliable method for the determination of all isoforms of teicoplanin applied in a low volume of sample is of real importance. Teicoplanin main components were extracted by a simple acetonitrile precipitation step and analysed on a C18 chromatographic column by a triple quadrupole MS with electrospray ionization. The method provides quantitative data over a linear range of 25-6400ng/mL with LOD 8.5ng/mL and LOQ 25ng/mL for total teicoplanin. The method was applied in plasma samples from neonates to support pharmacokinetic data and proved to be a reliable and fast method for the quantification of teicoplanin concentration levels in plasma of infants during therapy in Intensive Care Unit. PMID- 26896313 TI - Nitrification resilience and community dynamics of ammonia-oxidizing bacteria with respect to ammonia loading shock in a nitrification reactor treating steel wastewater. AB - The aim of this study was to investigate the nitrification resilience pattern and examine the key ammonia-oxidizing bacteria (AOB) with respect to ammonia loading shocks (ALSs) in a nitrification bioreactor treating steel wastewater. The perturbation experiments were conducted in a 4-L bioreactor operated in continuous mode with a hydraulic retention time of 10 d. Three sequential ALSs were given to the bioreactor (120, 180 and 180 mg total ammonia nitrogen (TAN)/L. When the first shock was given, the nitrification process completely recovered after 14 d of further operation. However, the resilience duration was significantly reduced to ~1 d after the second and third ALSs. In the bioreactor, Nitrosomonas aestuarii dominated the other AOB species, Nitrosomonas europaea and N. nitrosa, throughout the process. In addition, the population of N. aestuarii increased with ammonia utilization following each ALS; i.e., this species responded to acute ammonia overloadings by contributing to ammonia oxidation. This finding suggests that N. aestuarii could be exploited to achieve stable nitrification in industrial wastewaters that contain high concentrations of ammonia. PMID- 26896314 TI - Antibody-based fluorescent and fluorescent ratiometric indicators for detection of phosphotyrosine. AB - Fluorescent indicators for protein phosphorylation are very important in not only fundamental biology but also biomedical applications. In this study, we developed novel fluorescent and fluorescent ratiometric indicators for detection of phosphotyrosine (pTyr) derivatives. A single-chain antibody variable fragment (scFv) against phosphotyrosine was fluorescent-labeled by incorporation of tetramethylrhodamine (TAMRA)-linked nonnatural amino acid at the N- or C terminus. The TAMRA-labeled scFv showed fluorescence enhancement upon addition of pTyr-containing peptides based on antigen-dependent fluorescence quenching effect on TAMRA. The TAMRA-labeled scFv was further fused with enhanced green fluorescent protein (EGFP) to generate a double-labeled scFv for pTyr. In the absence of antigen, fluorescence resonance energy transfer (FRET) occurred from EGFP to TAMRA but TAMRA was quenched. The antigen-binding removed the quenching of TAMRA while FRET occurred without altering its efficiency. As a result of the FRET and antigen-dependent fluorescence quenching effect, the double-labeled scFv exhibited fluorescence ratio enhancement upon the antigen-binding. The fluorescent and fluorescent ratiometric indicators obtained in this study will become a novel tool for analysis of protein phosphorylation. Moreover, this strategy utilizes antibody derivatives, and therefore, can be easily applied to other antigen-antibody pairs to generate fluorescent ratiometric indicators for various target molecules. PMID- 26896315 TI - Cooperative hydration effect causes thermal unfolding of proteins and water activity plays a key role in protein stability in solutions. AB - The protein unfolding process observed in a narrow temperature range was clearly explained by evaluating the small difference in the enthalpy of hydrogen-bonding between amino acid residues and the hydration of amino acid residue separately. In aqueous solutions, the effect of cosolute on the protein stability is primarily dependent on water activity, aw, the role of which has been long neglected in the literature. The effect of aw on protein stability works as a power law so that a small change in aw is amplified substantially through the cooperative hydration effect. In the present approach, the role of hydrophobic interaction stands behind. This affects protein stability indirectly through the change in solution structure caused by the existence of cosolute. PMID- 26896316 TI - Characterization of Fe (III)-reducing enrichment culture and isolation of Fe (III)-reducing bacterium Enterobacter sp. L6 from marine sediment. AB - To enrich the Fe (III)-reducing bacteria, sludge from marine sediment was inoculated into the medium using Fe (OH)3 as the sole electron acceptor. Efficiency of Fe (III) reduction and composition of Fe (III)-reducing enrichment culture were analyzed. The results indicated that the Fe (III)-reducing enrichment culture with the dominant bacteria relating to Clostridium and Enterobacter sp. had high Fe (III) reduction of (2.73 +/- 0.13) mmol/L-Fe (II). A new Fe (III)-reducing bacterium was isolated from the Fe (III)-reducing enrichment culture and identified as Enterobacter sp. L6 by 16S rRNA gene sequence analysis. The Fe (III)-reducing ability of strain L6 under different culture conditions was investigated. The results indicated that strain L6 had high Fe (III)-reducing activity using glucose and pyruvate as carbon sources. Strain L6 could reduce Fe (III) at the range of NaCl concentrations tested and had the highest Fe (III) reduction of (4.63 +/- 0.27) mmol/L Fe (II) at the NaCl concentration of 4 g/L. This strain L6 could reduce Fe (III) with unique properties in adaptability to salt variation, which indicated that it can be used as a model organism to study Fe (III)-reducing activity isolated from marine environment. PMID- 26896317 TI - Preparation, Characterization, and Optimization of Folic Acid-Chitosan Methotrexate Core-Shell Nanoparticles by Box-Behnken Design for Tumor-Targeted Drug Delivery. AB - The objective of this study was to investigate the combined influence of independent variables in the preparation of folic acid-chitosan-methotrexate nanoparticles (FA-Chi-MTX NPs). These NPs were designed and prepared for targeted drug delivery in tumor. The NPs of each batch were prepared by coaxial electrospray atomization method and evaluated for particle size (PS) and particle size distribution (PSD). The independent variables were selected to be concentration of FA-chitosan, ratio of shell solution flow rate to core solution flow rate, and applied voltage. The process design of experiments (DOE) was obtained with three factors in three levels by Design expert software. Box Behnken design was used to select 15 batches of experiments randomly. The chemical structure of FA-chitosan was examined by FTIR. The NPs of each batch were collected separately, and morphologies of NPs were investigated by field emission scanning electron microscope (FE-SEM). The captured pictures of all batches were analyzed by ImageJ software. Mean PS and PSD were calculated for each batch. Polynomial equation was produced for each response. The FE-SEM results showed the mean diameter of the core-shell NPs was around 304 nm, and nearly 30% of the produced NPs are in the desirable range. Optimum formulations were selected. The validation of DOE optimization results showed errors around 2.5 and 2.3% for PS and PSD, respectively. Moreover, the feasibility of using prepared NPs to target tumor extracellular pH was shown, as drug release was greater in the pH of endosome (acidic medium). Finally, our results proved that FA-Chi-MTX NPs were active against the human epithelial cervical cancer (HeLa) cells. PMID- 26896319 TI - The Incidence of Peripheral Nerve Injury After Multimodal Perineural Anesthesia/Analgesia Does Not Appear to Differ from That Following Single-Drug Nerve Blocks (2011-2014). PMID- 26896318 TI - Intravenous magnesium sulfate for the management of severe hand, foot, and mouth disease with autonomic nervous system dysregulation in Vietnamese children: study protocol for a randomized controlled trial. AB - BACKGROUND: Over the last 15 years, hand, foot, and mouth disease (HFMD) has emerged as a major public health burden across the Asia-Pacific region. A small proportion of HFMD patients, typically those infected with enterovirus 71 (EV71), develop brainstem encephalitis with autonomic nervous system (ANS) dysregulation and may progress rapidly to cardiopulmonary failure and death. Although milrinone has been reported to control hypertension and support myocardial function in two small studies, in practice, a number of children still deteriorate despite this treatment. Magnesium sulfate (MgSO4) is a cheap, safe, and readily available medication that is effective in managing tetanus-associated ANS dysregulation and has shown promise when used empirically in EV71-confirmed severe HFMD cases. METHODS/DESIGN: We describe the protocol for a randomized, placebo-controlled, double-blind trial of intravenous MgSO4 in Vietnamese children diagnosed clinically with HFMD plus ANS dysregulation with systemic hypertension. A loading dose of MgSO4 or identical placebo is given over 20 min followed by a maintenance infusion for 72 h according to response, aiming for Mg levels two to three times the normal level in the treatment arm. The primary endpoint is a composite of disease progression within 72 h defined as follows: development of pre-specified blood pressure criteria necessitating the addition of milrinone, the need for ventilation, shock, or death. Secondary endpoints comprise these parameters singly, plus other clinical endpoints including the following: requirement for other inotropic agents; duration of hospitalization; presence of neurological sequelae at discharge in survivors; and neurodevelopmental status assessed 6 months after discharge. The number and severity of adverse events observed in the two treatment arms will also be compared. Based on preliminary data from a case series, and allowing for some losses, 190 patients (95 in each arm) will allow detection of a 50 % reduction in disease progression with 90 % power at a two sided 5 % significance level. DISCUSSION: Given the large numbers of HFMD cases currently being seen in hospitals in Asia, if MgSO4 is shown to be effective in controlling ANS dysregulation and preventing severe HFMD complications, this finding would be important to pediatric care throughout the region. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01940250 (Registered 22 August 2013). PMID- 26896321 TI - Pioglitazone may reduce cardiovascular events in high risk patients with prediabetes. PMID- 26896320 TI - Decellularized aortic homografts for aortic valve and aorta ascendens replacement. AB - OBJECTIVES: The choice of valve prosthesis for aortic valve replacement (AVR) in young patients is challenging. Decellularized pulmonary homografts (DPHs) have shown excellent results in pulmonary position. Here, we report our early clinical results using decellularized aortic valve homografts (DAHs) for AVR in children and mainly young adults. METHODS: This prospective observational study included all 69 patients (44 males) operated from February 2008 to September 2015, with a mean age of 19.7 +/- 14.6 years (range 0.2-65.3 years). In 18 patients, a long DAH was used for simultaneous replacement of a dilated ascending aorta as an extended aortic root replacement (EARR). Four patients received simultaneous pulmonary valve replacement with DPH. RESULTS: Thirty-nine patients (57%) had a total of 62 previous operations. The mean aortic cross-clamp time in isolated cases was 129 +/- 41 min. There was 1 conduit-unrelated death. The mean DAH diameter was 22.4 +/- 3.7 mm (range, 10-29 mm), the average peak gradient was 14 +/- 15 mmHg and the mean aortic regurgitation grade (0.5 = trace, 1 = mild) was 0.6 +/- 0.5. The mean effective orifice area (EOA) of 25 mm diameter DAH was 3.07 +/- 0.7 cm(2). DAH annulus z-values were 1.1 +/- 1.1 at implantation and 0.7 +/- 1.3 at the last follow-up. The last mean left ventricle ejection fraction and left ventricle end diastolic volume index was 63 +/- 7% and 78 +/- 16 ml/m(2) body surface area, respectively. To date, no dilatation has been observed at any level of the graft during follow-up; however, the observational time is short (140.4 years in total, mean 2.0 +/- 1.8 years, maximum 7.6 years). One small DAH (10 mm at implantation) had to be explanted due to subvalvular stenosis and developing regurgitation after 4.5 years and was replaced with a 17 mm DAH without complication. No calcification of the explanted graft was noticed intraoperatively and after histological analysis, which revealed extensive recellularization without inflammation. CONCLUSIONS: DAHs withstand systemic circulation, provide outstanding EOA and appear as an alternative to conventional grafts for AVR in young patients. EARR using DAH is a further option in aortic valve disease associated with aorta ascendens dilatation as it avoids the use of any prosthetic material. PMID- 26896322 TI - An in vitro method for determining the bioaccessibility of pharmaceuticals in wildlife. AB - Wildlife can be exposed to human pharmaceuticals via prey that have accumulated the compounds from wastewater, surface water, sediment, and soil. One factor affecting internal absorption of pharmaceuticals is bioaccessibility, the proportion of the compound that enters solution in the gastrointestinal tract. Currently, the bioaccessibility of most pharmaceuticals in prey remains unknown for most wildlife species. The authors evaluated the potential of a 2-compartment in vitro gastrointestinal tract model to compare the bioaccessibility of the antidepressant fluoxetine from invertebrate prey for birds and mammals. Samples of gizzard (or stomach) and intestinal-phase digestive juices were obtained from the in vitro models along with the residual solid material. High-performance liquid chromatographic analysis revealed that the bioaccessibility of fluoxetine in the avian in vitro models was statistically significantly lower than that in the mammalian models as a percentage of what was recovered; however, there were no statistically or biologically significant interspecies difference in terms of the amount recovered per gram of "food" inserted at the start of the simulation. This in vitro model provides a useful method of comparing the bioaccessibility of pharmaceuticals in different prey for species with different gastrointestinal conditions. There is merit for ecological risk assessments in further developing this in vitro approach to improve estimates of internal exposure for organics. Environ Toxicol Chem 2016;35:2349-2357. (c) 2016 SETAC. PMID- 26896323 TI - Bioaccessibility and bioavailability of methylmercury from seafood commonly consumed in North America: In vitro and epidemiological studies. AB - Methylmercury (MeHg) is a global contaminant of concern and human exposures are largely realized via seafood consumption. While it is assumed that 95-100% of the ingested MeHg from seafood reaches systemic circulation, recent in vitro studies have yielded results to suggest otherwise. Of the published studies to have characterized the bioaccessibility or bioavailability of MeHg from seafood, only a handful of seafood species have been characterized, there exists tremendous variability in data within and across species, few species of relevance to North America have been studied, and none of the in vitro studies have adapted results to an epidemiology study. The objective of the current study was two-fold: (a) to characterize in vitro MeHg bioaccessibility and bioavailability from ten commonly consumed types of seafood in North America; and (b) to apply the bioaccessibility and bioavailability data from the in vitro study to an existing human MeHg exposure assessment study. Raw seafood samples (cod, crab, halibut, salmon, scallop, shrimp, tilapia, and three tuna types: canned light, canned white, fresh) were purchased in Montreal and their MeHg concentrations generally overlapped with values reported elsewhere. The bioaccessibility of MeHg from these samples ranged from 50.1+/-19.2 (canned white tuna) to 100% (shrimp and scallop) of the amount measured in the raw undigested sample. The bioavailability of MeHg from these samples ranged from 29.3+/-10.4 (crab) to 67.4+/-9.7% (salmon) of the value measured in the raw undigested sample. There were significant correlations between the initial MeHg concentration in seafood with the percent of that Hg that was bioaccessible (r=-0.476) and bioavailable (r=-0.294). When the in vitro data were applied to an existing MeHg exposure assessment study, the estimated amount of MeHg absorbed into systemic circulation decreased by 25% and 42% when considering bioaccessibility and bioavailability, respectively. When the in vitro data were integrated into a regression model relating dietary MeHg intake from seafood with hair and blood Hg biomarkers, there were no differences in key model parameters when comparing the default model (that assumes 100% bioavailability) with models adjusted for the in vitro bioaccessibility and bioavailability data. In conclusion this work adds to a growing number of studies that together suggest that MeHg bioavailability from seafood may be less than 100%, but also documents the challenges when integrating such in vitro data into human exposure and risk assessments. PMID- 26896324 TI - Endogenous Action Selection Processes in Dorsolateral Prefrontal Cortex Contribute to Sense of Agency: A Meta-Analysis of tDCS Studies of 'Intentional Binding'. AB - BACKGROUND: Sense of agency is the experience of being in control of one's own actions and their consequences. The role of frontal cortex in this aspect of action control and awareness remains unclear. OBJECTIVE/HYPOTHESIS: Given the role of dorsolateral prefrontal cortex (DLPFC) in action selection, we predicted that DLPFC may contribute to sense of agency when participants select between multiple actions. METHODS: We performed a series of experiments by manipulating a range of task parameters related to action selection and action outcomes while participants were exposed to tDCS stimulation of the left DLPFC. We measured the temporal association between a voluntary action and its outcome using the intentional binding effect, as an implicit measure of sense of agency. RESULTS: Fixed-effect meta-analysis of our primary data showed a trend towards a frontal tDCS, together with considerable heterogeneity between our experiments. Classifying the experiments into subsets of studies, according to whether participants endogenously selected between alternative actions or not, explained 71% of this heterogeneity. Anodal stimulation of DLPFC increased the temporal binding of actions towards tones in the subset of studies involving endogenous action selection, but not in the other studies. CONCLUSIONS: DLPFC may contribute to sense of agency when participants selected between multiple actions. This enhanced feeling of control over voluntary actions could be related to the observed therapeutic effects of frontal tDCS in depression. PMID- 26896326 TI - Narrative Solutions: Using Preferred View of Self to Motivate Individual and Family Change. AB - This article describes refinements of the Narrative Solutions approach to individual and family therapy we first presented in Family Process 22 years ago. The centerpiece of this integrative (narrative-strategic) model is "preferred view of self," or the constellation of qualities people would like to see in themselves and have others see in them. We assume that problems generally involve one or more people mismanaging discrepancies or "gaps" between preferred views of self and either their actual behavior or how they see others seeing them and their behavior. Because clients are motivated to resolve such discrepancies, we use specifiable conversational strategies to help people (a) be clear about their preferred view of self, (b) notice gaps or discrepancies, and (c) summon resources to manage these gaps more effectively. Positive clinical effects of these strategic conversations can be rapid and dramatic. Case examples highlight applications to child and family problems, and we discuss some challenges and future directions for the Narrative Solutions approach. PMID- 26896325 TI - Age and gender related neuromuscular pattern during trunk flexion-extension in chronic low back pain patients. AB - BACKGROUND: The root mean square surface electromyographic activity of lumbar extensor muscles during dynamic trunk flexion and extension from standing has repeatedly been recommended to objectively assess muscle function in chronic low back pain patients. However, literature addressing older patients is sparse. This cross sectional study sought to examine differences in neuromuscular activation between age groups (>60 versus 40-60 versus <40 years) and sexes during a standardized trunk flexion-extension task. METHODS: A total of 216 patients (62 older, 84 middle-aged, 70 younger) performed maximum trunk extensions followed by trunk flexion extension testing thereby holding static positions at standing, half, and full trunk flexion. The lumbar extensor muscle activity and 3d accelerometric signals intended to monitor hip and trunk position angles were recorded from the L5 (multifidus) and T4 (semispinalis thoracis) levels. Permutation ANOVA with bootstrapped confidence intervals were performed to examine for age and gender related differences. Ridge-regressions investigated the impact of physical-functional and psychological variables to the half flexion relaxation ratio (i.e. muscle activity at the half divided by that in maximum flexion position). RESULTS: Maximum back extension torque was slightly but significantly higher in youngest compared to oldest patients if male and females were pooled. Normalized RMS-SEMG revealed highest lumbar extensor muscle activity at standing in the oldest and the female groups. Patients over 60 years showed lowest activity changes from standing to half (increments) and from half to the maximum flexion position (decrements) leading to a significantly lower half flexion relaxation ratio compared to the youngest patients. These oldest patients demonstrated the highest hip and lowest lumbothoracic changes of position angles. Females had higher regional hip and gross trunk ranges of movement compared to males. Lumbothoracic flexion and the muscle activity at standing had a significant impact on the half flexion relaxation ratio. CONCLUSIONS: The neuromuscular activation pattern and the kinematics in this trunk flexion extension task involving static half flexion position changed according to age and sex. The test has a good potential to discriminate between impaired and unimpaired neuromuscular regulation of back extensors in cLBP patients, thereby allowing the design of more individualized exercise programs. PMID- 26896327 TI - Quantitative Single-Embryo Profile of Drosophila Genome Activation and the Dorsal Ventral Patterning Network. AB - During embryonic development of Drosophila melanogaster, the maternal-to-zygotic transition (MZT) marks a significant and rapid turning point when zygotic transcription begins and control of development is transferred from maternally deposited transcripts. Characterizing the sequential activation of the genome during the MZT requires precise timing and a sensitive assay to measure changes in expression. We utilized the NanoString nCounter instrument, which directly counts messenger RNA transcripts without reverse transcription or amplification, to study >70 genes expressed along the dorsal-ventral (DV) axis of early Drosophila embryos, dividing the MZT into 10 time points. Transcripts were quantified for every gene studied at all time points, providing the first dataset of absolute numbers of transcripts during Drosophila development. We found that gene expression changes quickly during the MZT, with early nuclear cycle 14 (NC14) the most dynamic time for the embryo. twist is one of the most abundant genes in the entire embryo and we use mutants to quantitatively demonstrate how it cooperates with Dorsal to activate transcription and is responsible for some of the rapid changes in transcription observed during early NC14. We also uncovered elements within the gene regulatory network that maintain precise transcript levels for sets of genes that are spatiotemporally cotranscribed within the presumptive mesoderm or dorsal ectoderm. Using these new data, we show that a fine-scale, quantitative analysis of temporal gene expression can provide new insights into developmental biology by uncovering trends in gene networks, including coregulation of target genes and specific temporal input by transcription factors. PMID- 26896328 TI - Multivariate Analysis of Genotype-Phenotype Association. AB - With the advent of modern imaging and measurement technology, complex phenotypes are increasingly represented by large numbers of measurements, which may not bear biological meaning one by one. For such multivariate phenotypes, studying the pairwise associations between all measurements and all alleles is highly inefficient and prevents insight into the genetic pattern underlying the observed phenotypes. We present a new method for identifying patterns of allelic variation (genetic latent variables) that are maximally associated-in terms of effect size with patterns of phenotypic variation (phenotypic latent variables). This multivariate genotype-phenotype mapping (MGP) separates phenotypic features under strong genetic control from less genetically determined features and thus permits an analysis of the multivariate structure of genotype-phenotype association, including its dimensionality and the clustering of genetic and phenotypic variables within this association. Different variants of MGP maximize different measures of genotype-phenotype association: genetic effect, genetic variance, or heritability. In an application to a mouse sample, scored for 353 SNPs and 11 phenotypic traits, the first dimension of genetic and phenotypic latent variables accounted for >70% of genetic variation present in all 11 measurements; 43% of variation in this phenotypic pattern was explained by the corresponding genetic latent variable. The first three dimensions together sufficed to account for almost 90% of genetic variation in the measurements and for all the interpretable genotype-phenotype association. Each dimension can be tested as a whole against the hypothesis of no association, thereby reducing the number of statistical tests from 7766 to 3-the maximal number of meaningful independent tests. Important alleles can be selected based on their effect size (additive or nonadditive effect on the phenotypic latent variable). This low dimensionality of the genotype-phenotype map has important consequences for gene identification and may shed light on the evolvability of organisms. PMID- 26896329 TI - A General and Robust Framework for Secondary Traits Analysis. AB - Case-control designs are commonly employed in genetic association studies. In addition to the case-control status, data on secondary traits are often collected. Directly regressing secondary traits on genetic variants from a case control sample often leads to biased estimation. Several statistical methods have been proposed to address this issue. The inverse probability weighting (IPW) approach and the semiparametric maximum-likelihood (SPML) approach are the most commonly used. A new weighted estimating equation (WEE) approach is proposed to provide unbiased estimation of genetic associations with secondary traits, by combining observed and counterfactual outcomes. Compared to the existing approaches, WEE is more robust against biased sampling and disease model misspecification. We conducted simulations to evaluate the performance of the WEE under various models and sampling schemes. The WEE demonstrated robustness in all scenarios investigated, had appropriate type I error, and was as powerful or more powerful than the IPW and SPML approaches. We applied the WEE to an asthma case control study to estimate the associations between the thymic stromal lymphopoietin gene and two secondary traits: overweight status and serum IgE level. The WEE identified two SNPs associated with overweight in logistic regression, three SNPs associated with serum IgE levels in linear regression, and an additional four SNPs that were missed in linear regression to be associated with the 75th quantile of IgE in quantile regression. The WEE approach provides a general and robust secondary analysis framework, which complements the existing approaches and should serve as a valuable tool for identifying new associations with secondary traits. PMID- 26896330 TI - The Genetic Basis of Haploid Induction in Maize Identified with a Novel Genome Wide Association Method. AB - In vivo haploid induction (HI) triggered by pollination with special intraspecific genotypes, called inducers, is unique to Zea maysL. within the plant kingdom and has revolutionized maize breeding during the last decade. However, the molecular mechanisms underlying HI in maize are still unclear. To investigate the genetic basis of HI, we developed a new approach for genome-wide association studies (GWAS), termed conditional haplotype extension (CHE) test that allows detection of selective sweeps even under almost perfect confounding of population structure and trait expression. Here, we applied this test to identify genomic regions required for HI expression and dissected the combined support interval (50.34 Mb) of the QTL qhir1, detected in a previous study, into two closely linked genomic segments relevant for HI expression. The first, termed qhir11(0.54 Mb), comprises an already fine-mapped region but was not diagnostic for differentiating inducers and noninducers. The second segment, termed qhir12(3.97 Mb), had a haplotype allele common to all 53 inducer lines but not found in any of the 1482 noninducers. By comparing resequencing data of one inducer with 14 noninducers, we detected in the qhir12 region three candidate genes involved in DNA or amino acid binding, however, none for qhir11 We propose that the CHE test can be utilized in introgression breeding and different fields of genetics to detect selective sweeps in heterogeneous genetic backgrounds. PMID- 26896332 TI - A Note on the Dependence of Health on Age and Education. AB - When investigating relationships between education and health, one has to take age into account. Conditioning on age entails conditioning on surviving, which has been argued to lead to a potential selection bias. In this note, I argue that surviving should be considered as a necessary precondition for the relationships of interest and, therefore, not as a possible source of bias. I criticize models of health trajectories that do not condition on surviving. PMID- 26896331 TI - Conserved and Diverged Functions of the Calcineurin-Activated Prz1 Transcription Factor in Fission Yeast. AB - Gene regulation in response to intracellular calcium is mediated by the calcineurin-activated transcription factor Prz1 in the fission yeast Schizosaccharomyces pombe Genome-wide studies of the Crz1 and CrzA fungal orthologs have uncovered numerous target genes involved in conserved and species specific cellular processes. In contrast, very few target genes of Prz1 have been published. This article identifies an extensive list of genes using transcriptome and ChIP-chip analyses under inducing conditions of Prz1, including CaCl2 and tunicamycin treatment, as well as a ?pmr1 genetic background. We identified 165 upregulated putative target genes of Prz1 in which the majority contained a calcium-dependent response element in their promoters, similar to that of the Saccharomyces cerevisiae ortholog Crz1 These genes were functionally enriched for Crz1-conserved processes such as cell-wall biosynthesis. Overexpression of prz1(+)increased resistance to the cell-wall degradation enzyme zymolyase, likely from upregulation of theO-mannosyltransferase encoding gene omh1(+) Loss of omh1(+)abrogates this phenotype. We uncovered a novel inhibitory role in flocculation for Prz1. Loss of prz1(+)resulted in constitutive flocculation and upregulation of genes encoding the flocculins Gsf2 and Pfl3, as well as the transcription factor Cbf12. The constitutive flocculation of the ?prz1 strain was abrogated by the loss of gsf2(+) or cbf12(+) This study reveals that Prz1 functions as a positive and negative transcriptional regulator of genes involved in cell-wall biosynthesis and flocculation, respectively. Moreover, comparison of target genes between Crz1/CrzA and Prz1 indicate some conservation in DNA-binding specificity, but also substantial rewiring of the calcineurin-mediated transcriptional regulatory network. PMID- 26896333 TI - Strong inhibition of the polyol pathway diverts glucose flux to protein glycation leading to rapid establishment of secondary complications in diabetes mellitus. AB - BACKGROUND: Polyol pathway and protein glycation are implicated in establishing secondary complications in diabetes. Their relative contribution to the process needs to be evaluated. It is essential to understand why some aldose reductase inhibitors (ARIs) trials are successful while some have failed and to study their effect on protein glycation. METHODS: Aldose reductase (AR) was assayed using xylose as substrate; protein glycation was evaluated using total and specific fluorescence, fructoseamine and protein bound carbonyl content (PCO) measurements. Long term studies were carried out on streptozotocin induced diabetic rats for evaluation of urine parameters, tissue fluorescence. Anti cataract action was studied by lens culture studies. RESULTS: Epalrestat, a commercial ARI was also found to possess potent glycation inhibitory action. Long term experiments revealed strong protein glycation with higher concentration of citronellol (ARI) demonstrating shift in glucose flux. Treatment with epalrestat and limonene revealed improved urine parameters and tissue fluorescence. Lens culture studies revealed cataract formation at higher inhibition of AR while no lens opacity was observed at lower citronellol concentration and with limonene and epalrestat. CONCLUSION: Strong inhibition of AR shifts the glucose flux to protein glycation causing damage. ARIs possessing protein glycation inhibition are more useful in amelioration of secondary complications. PMID- 26896335 TI - Volumetry and biomechanical parameters detected by 3D and 2D ultrasound in patients with and without an abdominal aortic aneurysm. AB - The objective was to demonstrate the ability of ultrasound (US) with 3D properties to evaluate volumetry and biomechanical parameters of the aorta in patients with and without abdominal aortic aneurysm (AAA). Thirty-one patients with normal aortas (group 1), 46 patients with AAA measuring 3.0-5.5 cm (group 2) and 31 patients with AAA ? 5.5 cm (group 3) underwent a 2D/3D-US examination of the infra-renal aorta, and the images were post-processed prior to being analyzed. In the maximum diameter, the global circumferential strain and the global maximum rotation assessed by 2D speckle-tracking algorithms were compared among the three groups. The volumetry data obtained using 3D-US from 40 AAA patients were compared with the volumetry data obtained by a contemporary computed tomography (CT) scan. The median global circumferential strain was 2.0% (interquartile range (IR): 1.0-3.0), 1.0% (IR: 1.0-2.0) and 1.0% (IR: 1.0-1.75) in groups 1, 2 and 3, respectively (p < 0.001). The median global maximum rotation decreased progressively from group 1 to group 3 (1.38o (IR: 0.77-2.13), 0.80o (IR: 0.57-1.0) and 0.50o (IR: 0.31-0.75), p < 0.001). AAA volume estimations by 3D-US correlated well with CT (R(2) = 0.76). In conclusion, US with 3D properties is non-invasive and has the potential to evaluate volumetry and biomechanical characteristics of AAA. PMID- 26896334 TI - Accelerated decline of renal function in type 2 diabetes following severe hypoglycemia. AB - AIMS: This study aimed to evaluate whether the pronounced elevation in blood pressure during severe hypoglycemia is associated with subsequent renal insufficiency. METHODS: We conducted a 3-year cohort study to assess the clinical course of renal function in type 2 diabetes patients with or without blood pressure surge during severe hypoglycemia. RESULTS: Of 111 type 2 diabetes patients with severe hypoglycemia, 76 exhibited an extremely high systolic blood pressure before treatment, whereas 35 demonstrated no such increase (179.1 +/- 27.7 mmHg vs. 131.1 +/- 20.2 mmHg, P<0.001). At 12h after treatment, systolic blood pressure did not differ significantly (131.5 +/- 30.7 mmHg vs. 123.5 +/- 20.7 mmHg; P=0.39). The estimated glomerular filtration rate (GFR) before and at the time of severe hypoglycemia did not significantly differ between both groups. A multivariate Cox proportional hazards regression analysis revealed that blood pressure surge during severe hypoglycemia was independently associated with a composite outcome of a more than 15 mL/min/1.73 m(2) decrease in the estimated GFR and initiation of chronic dialysis (hazard ratio, 2.68; 95% confidence interval, 1.12-6.38; P=0.02). CONCLUSIONS: Renal function after severe hypoglycemia was significantly worse in type 2 diabetes patients with blood pressure surge during severe hypoglycemia than those without blood pressure surge. PMID- 26896336 TI - Interactive effects of global change factors on soil respiration and its components: a meta-analysis. AB - As the second largest carbon (C) flux between the atmosphere and terrestrial ecosystems, soil respiration (Rs) plays vital roles in regulating atmospheric CO2 concentration ([CO2 ]) and climatic dynamics in the earth system. Although numerous manipulative studies and a few meta-analyses have been conducted to determine the responses of Rs and its two components [i.e., autotrophic (Ra) and heterotrophic (Rh) respiration] to single global change factors, the interactive effects of the multiple factors are still unclear. In this study, we performed a meta-analysis of 150 multiple-factor (>=2) studies to examine the main and interactive effects of global change factors on Rs and its two components. Our results showed that elevated [CO2 ] (E), nitrogen addition (N), irrigation (I), and warming (W) induced significant increases in Rs by 28.6%, 8.8%, 9.7%, and 7.1%, respectively. The combined effects of the multiple factors, EN, EW, DE, IE, IN, IW, IEW, and DEW, were also significantly positive on Rs to a greater extent than those of the single-factor ones. For all the individual studies, the additive interactions were predominant on Rs (90.6%) and its components (~70.0%) relative to synergistic and antagonistic ones. However, the different combinations of global change factors (e.g., EN, NW, EW, IW) indicated that the three types of interactions were all important, with two combinations for synergistic effects, two for antagonistic, and five for additive when at least eight independent experiments were considered. In addition, the interactions of elevated [CO2 ] and warming had opposite effects on Ra and Rh, suggesting that different processes may influence their responses to the multifactor interactions. Our study highlights the crucial importance of the interactive effects among the multiple factors on Rs and its components, which could inform regional and global models to assess the climate-biosphere feedbacks and improve predictions of the future states of the ecological and climate systems. PMID- 26896337 TI - The Effect of Changing Scan Mode on Trabecular Bone Score Using Lunar Prodigy. AB - Trabecular bone score (TBS) is a measure of gray scale homogeneity that correlates with trabecular microarchitecture and is an independent predictor of fracture risk. TBS is being increasingly used in the assessment of patients at risk of osteoporosis and has recently been incorporated into FRAX(r). GE Lunar machines acquire spine scans using 1 of 3 acquisition modes depending on abdominal tissue thickness (thin, standard, and thick). From a database review, 30 patients (mean body mass index: 30.8, range 26.2-34.1) were identified who had undergone lumbar spine DXA scans (GE Lunar Prodigy, software 14.10; Lunar Radiation Corporation, Madison, WI) in both standard mode and thick mode, on the same day with no repositioning. Lumbar spine bone mineral density (L1-L4) and TBS were derived from the 30 paired spine scans. There was no significant difference in lumbar spine bone mineral density between the 2 scanning modes. There were, however, significant higher TBS values from the spine scans acquired in thick mode compared to the TBS values derived from spine acquisitions in standard mode (mean TBS difference: 0.24 [20%], standard deviation +/-0.10). In conclusion, these preliminary data suggest that TBS values acquired in the GE Lunar Prodigy are dependent on the scanning mode used. Further evaluation is required to confirm the cause and develop appropriate protocols. PMID- 26896339 TI - Discovery of New Substrates for LuxAB Bacterial Bioluminescence. AB - In this article, four novel substrates with long halftime have been designed and synthesized successfully for luxAB bacterial bioluminescence. After in vitro and in vivo biological evaluation, these molecules can emit obvious bioluminescence emission with known bacterial luciferase, thus indicating a new promising approach to developing the bacterial bioluminescent system. PMID- 26896338 TI - Nucleosome dynamics: Sequence matters. AB - About three quarter of all eukaryotic DNA is wrapped around protein cylinders, forming nucleosomes. Even though the histone proteins that make up the core of nucleosomes are highly conserved in evolution, nucleosomes can be very different from each other due to posttranslational modifications of the histones. Another crucial factor in making nucleosomes unique has so far been underappreciated: the sequence of their DNA. This review provides an overview of the experimental and theoretical progress that increasingly points to the importance of the nucleosomal base pair sequence. Specifically, we discuss the role of the underlying base pair sequence in nucleosome positioning, sliding, breathing, force-induced unwrapping, dissociation and partial assembly and also how the sequence can influence higher-order structures. A new view emerges: the physical properties of nucleosomes, especially their dynamical properties, are determined to a large extent by the mechanical properties of their DNA, which in turn depends on DNA sequence. PMID- 26896342 TI - Patient End-of-Life Experiences for Pediatric Trainees: Spanning the Educational Continuum. AB - Background End-of-life care for a child is an emotionally charged experience for pediatric trainees. Objectives Describe the progression of medical trainee experiences with end-of-life care and determine personal/professional experiences that facilitated integration of experiences. Methods Medical students (MS4) and pediatric residents (PL-1-3) completed a 30-question survey about experiences with patient deaths and integration of these experiences. Results A total of 307 of 404 residents (76%) participated. Mean number of deaths ranged from 3.0 to 6.5 in the prior 12 months, and the most common location was neonatal intensive care unit or pediatric intensive care unit. In total, 18% to 27% experienced a death in their personal life. Between 26% and 41% of the residents made contact with a family after death, and 15% to 35% attended a funeral. Characteristics of good deaths included good communication and discussion of end-of-life issues. Conclusions Trainees experienced patient deaths along the educational continuum. These findings have implications for the optimal timing and method of end-of-life care education. PMID- 26896341 TI - The "Battle" of Managing Language Barriers in Health Care. AB - Providing safe and high-quality health care for children whose parents have limited English proficiency (LEP) remains challenging. Reports of parent perspectives on navigating language discordance in health care are limited. We analyzed portions of 48 interviews focused on language barriers from 2 qualitative interview studies of the pediatric health care experiences of LEP Latina mothers in 2 urban US cities. We found mothers experienced frustration with health care and reported suboptimal accommodation for language barriers. Six themes emerged relevant to health care across settings: the "battle" of managing language barriers, preference for bilingual providers, negative bias toward interpreted encounters, "getting by" with limited language skills, fear of being a burden, and stigma and discrimination experienced by LEP families. Parents' insights highlight reasons why effective language accommodation in health care remains challenging. Partnering with families to address the management of language barriers is needed to improve health care quality and safety for LEP patients and families. PMID- 26896344 TI - Mechanisms of vertebrate embryo segmentation. PMID- 26896343 TI - Introduction to the Special Issue on Bone. PMID- 26896340 TI - Metabolic syndrome and pre-diabetes contribute to racial disparities in breast cancer outcomes: hypothesis and proposed pathways. AB - BACKGROUND: Women with obesity and type 2 diabetes (T2D) are at greater risk of dying from breast cancer than women without these conditions. Obesity and T2D are associated with insulin resistance and endogenous hyperinsulinemia and are more common in Black women. There is increasing disparity in breast cancer mortality between Black and White women in the USA. We hypothesize that insulin resistance and endogenous hyperinsulinemia in Black women with breast cancer contribute to their greater breast cancer mortality and are associated with increased insulin receptor signalling in tumours. METHODS: We will recruit 350 Black women and 936 White women with newly diagnosed breast cancer. We will determine the presence or absence of the metabolic syndrome/pre-diabetes and insulin resistance by measuring body mass index, waist circumference, lipids, blood pressure, glucose, insulin-like growth factor binding protein 1 and insulin. Breast cancer prognosis will be determined by a Nottingham Prognostic Index (NPI), with poor prognosis being defined as NPI >4.4. Tumour insulin receptor signalling will be determined by immunohistochemistry. Insulin receptor subtype expression will be measured using Nanostring. Analysis of these factors will determine whether endogenous hyperinsulinemia is associated with a worse prognosis in Black women than White women and increased tumour insulin receptor signalling. CONCLUSIONS: The results of this study will determine if the metabolic syndrome and pre-diabetes contribute to racial disparities in breast cancer mortality. It may provide the basis for targeting systemic insulin resistance and/or tumour insulin receptor signalling to reduce racial disparities in breast cancer mortality. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26896345 TI - Pharmacokinetics of dexmedetomidine, MK-467, and their combination following intravenous administration in male cats. AB - This study characterized the pharmacokinetics of dexmedetomidine, MK-467, and their combination following intravenous bolus administration to cats. Seven 6- to year-old male neutered cats, weighting 5.1 +/- 0.7 kg, were used in a randomized, crossover design. Dexmedetomidine [12.5 (D12.5) and 25 (D25) MUg/kg], MK-467 [300 MUg/kg (M300)] or dexmedetomidine (25 MUg/kg) and MK-467 [75, 150, 300 or 600 MUg/kg-only the plasma concentrations in the 600 MUg/kg group (D25M600) were analyzed] were administered intravenously, and blood was collected until 8 hours thereafter. Plasma drug concentrations were analyzed using liquid chromatography/mass spectrometry. A two-compartment model best fitted the data. Median (range) volume of the central compartment (mL/kg), volume of distribution at steady state (mL/kg), clearance (mL min/kg) and terminal half-life (min) were 342 (131-660), 829 (496-1243), 14.6 (9.6-22.7) and 48 (40-69) for D12.5; 296 (179 982), 1111 (908-2175), 18.2 (12.4-22.9) and 52 (40-76) for D25; 653 (392-927), 1595 (1094-1887), 22.7 (18.5-36.4) and 48 (35-60) for dexmedetomidine in D25M600; 117 (112-163), 491 (379-604), 3.0 (2.0-4.5) and 122 (99-139) for M300; and 147 (112-173), 462 (403-714), 2.8 (2.1-4.8) and 118 (97-172) for MK-467 in D25M600. MK-467 moderately but statistically significantly affected the disposition of dexmedetomidine, whereas dexmedetomidine minimally affected the disposition of MK 467. PMID- 26896346 TI - Resolution of Enantiomers of (RS)-Baclofen by Ligand-Exchange Thin-Layer Chromatography. AB - A new chromatographic method has been developed for direct enantioresolution of (RS)-baclofen by ligand-exchange thin-layer chromatography (TLC) adopting two different approaches; (A) TLC plates were prepared by mixing the ligand exchange reagents (LER) with silica gel slurry and the chromatograms were developed with different achiral solvents or solvents having no chiral additive, and (B) the LER consisting of Cu(II)-L-amino acid complex was used as chiral mobile phase additive and the plain plates of silica gel having no chiral selector were used. Cu(II) acetate and four L-amino acids (namely, L-tryptophan, L-histidine, L proline and L-phenylalanine) were used for the preparation of LERs. Spots were located by the use of iodine vapor. Effect of temperature and the mole ratio of Cu(II)-to-amino acid on enantioresolution were also studied. The results for the two methods have been compared, and the issue of involvement of the Cu(II) cation for the best performance of the two methods has been discussed with respect to the same mobile phase. L-Trp proved to be a good ligand using a common mobile phase in each case. PMID- 26896347 TI - Rapid Identification of Flavonoid Constituents Directly from PTP1B Inhibitive Extract of Raspberry (Rubus idaeus L.) Leaves by HPLC-ESI-QTOF-MS-MS. AB - Many potential health benefits of raspberry (Rubus idaeus L.) leaves were attributed to polyphenolic compounds, especially flavonoids. In this study, the methanol extract of R. idaeus leaves showed significant protein tyrosine phosphatase-1B (PTP1B) inhibitory activity with IC50 value of 3.41 +/- 0.01 ug mL(-1) Meanwhile, a rapid and reliable method, employed high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry, was established for structure identification of flavonoids from PTP1B inhibitive extract of R. idaeus leaves using accurate mass measurement and characteristic fragmentation patterns. A total of 16 flavonoids, including 4 quercetin derivatives, 2 luteolin derivatives, 8 kaempferol derivatives and 2 isorhamnetin derivatives, were identified. Compounds 3: and 4: , Compounds 6: and 7: and Compounds 15: and 16: were isomers with different aglycones and different saccharides. Compounds 8: , 9: and 10: were isomers with the same aglycone and the same saccharide but different substituent positions. Compounds 11: and 12: were isomers with the same aglycone but different saccharides. Compounds 2: , 8: , 9: and 10: possessed the same substituent saccharide of glycuronic acid. Most of them were reported inR. idaeus for the first time. PMID- 26896349 TI - Excretion of Morroniside in Rat Urine After Single Oral and Intravenous Administration. AB - This study was designed to develop a sensitive, simple and rapid method for the quantitation of morroniside in rat urine using high-performance liquid chromatography-tandem mass spectrometry (LC-MS-MS) and to investigate the excretion of morroniside in rat urine. The mobile phase consisted of water acetonitrile (gradient elution) at a flow rate of 0.4 mL/min. Detection was performed using positive-ion electrospray ionization in multiple reaction monitoring (MRM) modes. And the detection of morroniside in rat urine by the LC MS-MS was accurate and precise from 1.0 to 2,500 ng/mL (a correlation coefficient of 0.9953). The recoveries and matrix effects were all in line with the biological sample measurement requirements. The intraday accuracy was 88.68 105.78% with precision of 6.50-11.19% and the interday accuracy was 95.77-102.43% with precision of 7.08-10.40%. Excretion data of morroniside in rat urine indicated that 21.430/00 (i.g.) and 100.35% (i.v.) of the dose administered was excreted as unconverted form, respectively. And the maximal excretion rate was 27.57 and 482.42 MUg/h after oral and intravenous administration, respectively. These results indicated that the developed method has satisfactory sensitivity, accuracy and precision for the quantification of morroniside in rat urine. PMID- 26896348 TI - Validation and Application of an LC-MS-MS Method for the Determination of Ceftizoxime in Human Serum and Urine. AB - Ceftizoxime sodium is a third-generation cephalosporin available for parenteral administration, which is mainly excreted through urine. A rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) method was developed and validated for the determination of ceftizoxime in human serum and urine. The samples were purified by protein precipitation and separated on an XTerra Phenyl column (4.6 * 50 mm, 5 um). Electrospray ionization in the positive ion mode and multiple reaction monitoring were used to monitor the ion transitions at m/z 383.9/227.0. The results revealed that the method had excellent selectivity. The linear range covered from 2.50 to 10,000 ng/mL in serum and from 0.500 to 50.0 ug/mL in urine, respectively. Intra-batch and inter batch precisions (in terms of relative standard deviation) were all <15% and the accuracies (in terms of relative error) were within the range of +/- 15%. The lower limit of quantification, stability and extraction recovery were also validated and satisfied the criteria of validation. Finally, the method was successfully applied to a pharmacokinetic study of Chinese elderly healthy subjects after intravenous administration. The Cmax values in serum were 34,721.3 +/- 5,697.3 ng/mL. Serum concentrations declined with t1/2 of 2.57 +/- 0.22 h. PMID- 26896350 TI - Study on the Alkaloids in Tibetan Medicine Aconitum pendulum Busch by HPLC-MSn Combined with Column Chromatography. AB - A rapid, convenient and effective identification method of alkaloids was established and an attempt on isolating and analyzing the alkaloids in Aconitum pendulum Busch was conducted successfully. In this article, four high-content components including deoxyaconitine, benzoylaconine, aconine and neoline were isolated by using column chromatography. HPLC-MS(n)was employed to deduce the regulations of fragmentation of diterpenoid alkaloids which displayed a characteristic behavior of loss of CO(28u), CH3COOH(60u), CH3OH(32u), H2O(18u) and C6H5COOH(122u). Then, according to fragmentation regulation of mass spectrometry, 42 alkaloids were found inA. pendulum Among them, 38 compounds were identified and 29 alkaloids were reported for the first time for this herb. Therefore, this means that HPLC-MS(n)combined with column chromatography could work as an effective and reliable tool for rapid identification of the chemical components of herbal medicine. PMID- 26896351 TI - Age- and Sex-Related Changes in Bone Microarchitecture and Estimated Strength: A Three-Year Prospective Study Using HRpQCT. AB - Although projections from cross-sectional studies have shown that bone loss leading to osteoporosis begins around menopause in women and later in life in men, this has not been examined longitudinally in population-based studies using high-resolution technology capable of distinguishing cortical (Ct) and trabecular (Tb) bone microarchitecture. The aim of this 3-year prospective study was to investigate age- and sex-related changes in bone compartment-specific geometry, volumetric bone mineral density (vBMD), microarchitecture, and estimated strength. The distal radius and tibia were imaged at baseline and after 3 years (median 3.0; range, 2.7 to 3.9 years) using high-resolution peripheral computed tomography (HRpCT) in an age- and sex-stratified, population-based, random sample of white men and women (n = 260) aged 21 to 82 years. In general, at the radius and tibia there was a moderate annual increase in cortical thickness (Ct.Th) that seemed to offset the increase in cortical porosity (Ct.Po), resulting in net annual increase in cortical vBMD (Ct.vBMD) in premenopausal women and young men. With advancing age, postmenopausal women displayed significant bone loss with decreased trabecular vBMD (Tb.vBMD) (due to loss of entire trabeculae) and Ct.vBMD (manifested as increase in Ct.Po and decrease in Ct.Th) at the radius, and a decline in Ct.vBMD (with increasing Ct.Po) at the tibia, resulting in loss of estimated bone strength. In contrast, men had a lower rate of bone loss with advancing age with smaller increases in Ct.Po at both the skeletal sites. In summary, the pattern of bone loss in men and women was discrepant, with women losing more bone than men with aging, although with a dominance of cortical over trabecular bone loss at the peripheral sites in both sexes. This conforms to epidemiological evidence that most fractures occurring in old age are predominantly at cortical peripheral sites, with women having a higher incidence of fractures than men at any given age. (c) 2016 American Society for Bone and Mineral Research. PMID- 26896353 TI - Feedback to GPs reduces antibiotic prescribing, study finds. PMID- 26896352 TI - Efficacy and safety of Qi-Wei-Qing-Yan aerosol in treatment of acute pharyngitis (lung-stomach excess-heat syndrome): study protocol for a randomized controlled trial. AB - BACKGROUND: Acute pharyngitis accounts for an estimated 15 million patient visits in the United States. However, there is no proven effective and safe treatment. Although Chinese herbal medicine is widely used in the treatment of acute pharyngitis, there is a lack of evidence-based data. Despite several clinical trials conducted in this setting, no randomized placebo-controlled trial has been performed to date. This trial aims to investigate the efficacy and safety of Qi Wei-Qing-Yan aerosol (QWQYA), a Chinese herbal prescription, compared with a placebo aerosol in the treatment of acute pharyngitis with lung-stomach excess heat syndrome. METHODS/DESIGN: This is a prospective, multicenter, randomized, double-blinded, parallel-group, placebo-controlled trial. A total of 420 adult patients, of either sex, with acute pharyngitis will be enrolled from seven study sites across China. All patients will be randomly allocated to one of three parallel treatment groups: (1) QWQYA with the current propellant, (2) QWQYA with a previous propellant, and (3) the placebo aerosol with the current propellant. The study medication will be administered into the pharyngeal region in three sprays thrice daily for 5 consecutive days. The primary outcome measures are time to complete resolution of sore throat and relief rate of sore throat. Secondary outcome measures include resolution rate of sore throat, time to relief of sore throat, intensity of sore throat, and change of traditional Chinese medicine syndrome score and clinical signs score from baseline to post-treatment, as well as the occurrence of any adverse events. DISCUSSION: This will be the first clinical trial to investigate the efficacy and safety of QWQYA in the treatment of acute pharyngitis in an adult population in a multicenter, randomized, double blinded, parallel-group, placebo-controlled manner. Not only might it establish the basis for the efficacy and safety of QWQYA in treating acute pharyngitis, but it might also provide evidence to support the use of Chinese herbal medicine in treating acute pharyngitis and thus support an alternative treatment option for management of acute pharyngitis. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-IPR-15005991. PMID- 26896354 TI - Pulmonary vein stenosis--novel strategies for a challenging and resistant condition? PMID- 26896355 TI - Fontan at 40: Midlife crisis? PMID- 26896356 TI - Risk calculators are useful but.... PMID- 26896358 TI - Discussion. PMID- 26896357 TI - Psoas muscle size as a frailty measure for open and transcatheter aortic valve replacement. AB - OBJECTIVE: To evaluate the use of sarcopenia as a frailty assessment tool for patients with aortic stenosis undergoing surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR). METHODS: The study cohort comprised 295 patients who underwent either SAVR (n = 156) or TAVR (n = 139). The mean preoperative Society of Thoracic Surgeons mortality risk score was 4.7%. Preoperative computed tomography (CT) scans were used to calculate gender standardized total psoas area (TPA), as a validated measure of sarcopenia. RESULTS: For the entire cohort, independent predictors of a composite measure of 30-day death, stroke, renal failure, prolonged ventilation, and deep wound infection included preoperative STS major morbidity and mortality risk score (odds ratio [OR], 91.1; P = .02) and TPA (OR, 0.5; P = .024). Two-year survival was 85.7% in patients with sarcopenia, compared with 93.8% in patients without sarcopenia (P = .02). Independent predictors of late survival included TPA (hazard ratio, 0.47; P = .02). Male sex (OR, 0.52; P = .04) and TPA (OR, 0.6; P = .001) were predictive of high resource utilization. A separate analysis by treatment group found that TPA predicted high resource utilization after SAVR (OR, 0.4; P < .001), but not after TAVR (P = .66). CONCLUSIONS: CT scan-derived measurement of TPA as an objective frailty assessment tool predicts early morbidity and mortality, high resource utilization, and late survival after treatment for aortic stenosis. The correlation observed between sarcopenia and resource utilization after SAVR versus TAVR suggests that this simple and reproducible risk assessment tool also may help identify those patients who will derive optimal benefit from catheter-based therapy. PMID- 26896359 TI - Postoperative medication management after surgical ablation: Clarifying the role of amiodarone therapy. PMID- 26896361 TI - Discussion. PMID- 26896360 TI - Pretreatment with bone marrow-derived mesenchymal stromal cell-conditioned media confers pulmonary ischemic tolerance. AB - OBJECTIVE: Mesenchymal stromal cell-based therapies have demonstrated efficacy in treating a variety of diseases. Despite the potential benefits, there are still significant hurdles that need to be overcome for clinical use. We describe a cell free-based immunotherapy approach for inducing pulmonary ischemic tolerance by using mesenchymal stromal cell-conditioned media. METHODS: In our well established lung ischemia-reperfusion model, we pretreated with mesenchymal stromal cell-conditioned media 30 minutes before injury. To determine the degree of lung injury, we assessed for changes in lung vascular permeability, proinflammatory cytokines and cellular infiltrates in bronchoalveolar lavage, and histopathology. Macrophage and T-cell subsets were assessed by immunohistochemistry. RESULTS: Pretreatment with mesenchymal stromal cell conditioned media conferred protection against lung ischemia-reperfusion injury. This protection is characterized by a significant reduction in proinflammatory cytokines, a decrease in infiltrating inflammatory cells, and increases in M2 like macrophages and regulatory T cells. CONCLUSIONS: Cell-free mesenchymal stromal cell-conditioned media therapy confers pulmonary ischemic tolerance. This therapy uses paracrine factors that provide beneficial protective effects by immunomodulating the inflammatory response in resident and infiltrating cell subsets. PMID- 26896362 TI - Prolonged continuous-flow left ventricular assist device support and posttransplantation outcomes: A new challenge. AB - OBJECTIVE: To assess outcomes after cardiac transplantation in patients receiving long-term continuous-flow left ventricular assist device (CF-LVAD) support. METHODS: The United Network of Organ Sharing Database was used to identify 7808 heart transplant recipients between January 2011 and March 2014, 2456 (31.5%) of whom were bridged with CF-LVAD. Recipients were stratified by CF-LVAD duration: group 1, <1 year (n = 1590; 64.7%); group 2, 1 to 2 years (n = 599; 24.4%); and group 3, >2 years (n = 267; 10.9%). RESULTS: Compared with patients in groups 1 and 2, patients in group 3 spent more time as status 1A, had a greater body mass index and higher serum creatinine level, more often received blood transfusions and antibiotics, and more often developed device-related infection and life threatening arrhythmia before transplantation. Kaplan-Meier analysis revealed statistically significant lower survival rates in group 3 compared with groups 1 and 2, at both 30 days (92.9% vs 96.4% vs 95.5%; group 1 vs group 3, P = .009) and 2 years (78.9% vs 88.2% vs 86.3%; group 1 vs group 3, P = .001) posttransplantation. Multivariable analyses identified duration of CF-LVAD support as a significant factor for 2-year posttransplantation mortality (hazard ratio, 1.16; 95% confidence interval, 1.01-1.34; P = .040). CONCLUSIONS: A bridge to-transplant (BTT) strategy with a CF-LVAD has become standard care for patients with advanced heart failure. Duration of CF-LVAD support is associated with increased midterm mortality, warranting early transplantation in the modern BTT era. PMID- 26896363 TI - Use of transthoracic cryoanalgesia during the Nuss procedure. PMID- 26896364 TI - Cardioprotective effect of propofol cannot be extrapolated from the placebo controlled, randomized controlled trial. PMID- 26896365 TI - Prophylactic amiodarone: Use it or not? PMID- 26896366 TI - Prophylactic amiodarone reduced the recurrence of atrial arrhythmias. PMID- 26896367 TI - Off-pump coronary artery bypass grafting versus conventional coronary artery bypass grafting: What we don't know. PMID- 26896368 TI - Missing the forest for the trees. PMID- 26896369 TI - OPCAB versus conventional CABG: What we learn today will help addressing the future. PMID- 26896370 TI - Management of augmentation of restless legs syndrome with rotigotine: a 1-year observational study. AB - AIM: The aim of this study is to assess the effect of switching to rotigotine transdermal patch on severity of restless legs syndrome (RLS) in patients who experienced acute augmentation with previous oral dopaminergics. METHODS: In this 13-month observational study, adults with moderate-to-severe RLS and augmentation were switched to rotigotine per the physician's independent decision. Assessments included Clinical Global Impression severity score (CGI-1); (primary), treatment regimen for switching (secondary), RLS-6, International RLS Study Group Rating Scale (IRLS), and augmentation severity rating scale (ASRS). RESULTS: A total of 99 patients received rotigotine, of whom 46 completed observational period, and 43 were assessed for effectiveness. A total of 5 patients switched to rotigotine after a >1-day drug holiday, 23 switched overnight, 9 had an overlapping switch, and 6 received ongoing oral dopaminergics with rotigotine for >=28 days. Of the 99 patients, 57 took concomitant RLS medications (excluding switching medications) on at least 1 day. At the final visit, median change in CGI-1 (Hodges-Lehman estimate [95% CI]) was -2.0 (-2.5, -1.50); 37 of the 43 patients improved by >=1 CGI-1 category, and 16 of 43 were responders (>=50% improvement). RLS-6 and IRLS scores also improved. Patients had median ASRS of 0 at the final visit indicating "no worsening/occurrence of augmentation." ASRS item 1 showed a shift in mean time of symptom onset (24-h clock) from 12:38 (baseline) to 18:25 (final visit). Most common reasons for withdrawal of rotigotine were adverse events (26 patients) and lack of efficacy (14 patients). CONCLUSIONS: Switching from oral therapies to rotigotine was effective in improving RLS symptoms in 37 of the 43 patients (from the original population of 99 patients) who remained in the study over 13 months. CLINICAL TRIAL REGISTRATION: ClinicalTrials.govNCT01386944. PMID- 26896372 TI - Leptomeningeal transthyretin-type amyloidosis presenting as acute hydrocephalus and subarachnoid hemorrhage. AB - We present a report of a 47-year-old woman with developmental delay who presented with subarachnoid hemorrhage and acute hydrocephalus. She did not have an aneurysm, but there was symmetric calcification and gadolinium-enhancement of the meninges within the Sylvian fissure. Biopsy and genetic testing confirmed transthyretin-type amyloidosis. It is important to consider such rare causes in atypical presentations of non-aneurysmal subarachnoid hemorrhage. PMID- 26896373 TI - Electrophysiological Evidence of Atypical Spatial Attention in Those with a High Level of Self-reported Autistic Traits. AB - Selective attention is atypical in individuals with autism spectrum conditions. Evidence suggests this is also the case for those with high levels of autistic traits. Here we investigated the neural basis of spatial attention in those with high and low levels of self-reported autistic traits via analysis of ERP deflections associated with covert attention, target selection and distractor suppression (the N2pc, NT and PD). Larger N2pc and smaller PD amplitude was observed in those with high levels of autistic traits. These data provide neural evidence for differences in spatial attention, specifically, reduced distractor suppression in those with high levels of autistic traits, and may provide insight into the experience of perceptual overload often reported by individuals on the autism spectrum. PMID- 26896374 TI - Feasibility of high-pitch dual-source low-dose chest CT: Reduction of radiation and cardiac artifacts. AB - PURPOSE: To compare the radiation dose and image quality, focused mainly on cardiac pulsation artifact, between high-pitch low-dose chest computed tomography (HP-LDCT) and standard low-dose chest CT (LDCT). PATIENTS AND METHODS: One hundred patients underwent HP-LDCT (50 patients) or LDCT (50 patients). Scan parameters were the same except for the pitch and gantry rotation time: 3.0 vs. 1.2 and 0.28s vs. 0.5s, respectively. Objective image noise at five regions and subjective image quality, such as noise, artifacts, cardiac pulsation artifacts, and overall diagnostic acceptability, were evaluated using a five-point scale. The significance level for all tests was set at P<0.05. RESULTS: The dose-length products (DLPs) with HP-LDCT and LDCT were 90.2+/-4.3mGycm and 103.1+/-6.4mGycm, respectively (P<0.01). DLP of HP-LDCT showed a 13% reduction versus LDCT. Objective image noise was not significantly different. Cardiac pulsation artifacts showed a significant reduction on HP-LDCT (P<0.01). Other subjective image quality parameters of HP-LDCT were similar to those of LDCT. The overall diagnostic acceptability of HP-LDCT was better than that of LDCT (P<0.01). CONCLUSIONS: HP-LDCT showed a 13% mean radiation dose reduction with no deterioration in image quality due to cardiac pulsation artifacts. PMID- 26896371 TI - Benefits of stereotactic ablative radiotherapy combined with incomplete transcatheter arterial chemoembolization in hepatocellular carcinoma. AB - BACKGROUND: This study aimed to evaluate the effect of stereotactic ablative radiotherapy (SABR) after incomplete transcatheter arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) patients. METHODS: The study enrolled 178 HCC patients initially treated with TACE between 2006 and 2011. Patients were included if they had Barcelona Clinic Liver Cancer stage 0 or A, <=3 nodules with a total sum of longest diameter <=10 cm, Child-Turcotte-Pugh score of <=7, no major vessel invasion, and no extra-hepatic metastases. RESULTS: Twenty-four patients achieved a complete response to TACE (group 1). Among those with incomplete response, 47 patients received other curative treatments (group 2), 37 received SABR (group 3), and 70 received non-curative treatments (group 4). The 2 year overall survival (OS) rates for groups 1, 2, 3, and 4 were 88 %, 81 %, 73 %, and 54 %, respectively. The corresponding 5-year OS rates were 50 %, 58 %, 53 %, and 28 %, respectively. CONCLUSIONS: Patients treated with SABR after incomplete TACE had similar survival outcomes to those achieving complete response to TACE or receiving curative treatments. However, patients receiving non-curative treatments had significantly lower survival rates than the other groups. Therefore, if SABR was indicated at the initial diagnosis, it might be recommended after TACE failure. PMID- 26896375 TI - Black carbon aerosol from biochar threats its negative emission potential. PMID- 26896376 TI - Evaluation of a di-O-methylated glycan as a potential antigenic target for the serodiagnosis of human toxocariasis. AB - Serodiagnosis of human toxocariasis is based on the detection of specific IgG antibodies by the enzyme-linked immunosorbent assay (ELISA) using Toxocara larvae excretory-secretory (TES) antigens, but its production is a laborious and time consuming process being also limited by the availability of adult females of T. canis as source for ova to obtain larvae. Chemical synthesis of the di-O methylated (DiM) glycan structure found in the TES antigens has provided material for studying the antibody reactivity in a range of mammalian hosts, showing reactivity with human IgM and IgG. In this study, we have evaluated the performance of the DiM glycan against a panel of sera including patients with toxocariasis (n = 60), patients with other helminth infections (n = 75) and healthy individuals (n = 94), showing that DiM is able to detect IgG antibodies with a sensitivity and specificity of 91.7% and 94.7%, respectively, with a very good agreement with the TES antigens (kappa = 0.825). However, cross-reactivity was observed in some sera from patients with ascariasis, hymenolepiasis and fascioliasis. These results show that the DiM glycan could be a promising antigenic tool for the serodiagnosis of human toxocariasis. PMID- 26896377 TI - beta-lactoglobulin-pectin Nanoparticle-based Oral Drug Delivery System for Potential Treatment of Colon Cancer. AB - Colon cancer is one of the most common internal malignancies, and conventional chemotherapy is not effective in its treatment. Nanoparticles hold tremendous potential as an effective drug delivery system. The physicochemical properties of beta-lactoglobulin, the main whey protein of cow's milk, such as its stability at low pH, its resistance to gastric protease, and its ability to bind hydrophobic ligands, give it potential for transporting drugs specifically for colon cancer. In the present research, beta-lactoglobulin-pectin nanoparticles were designed to transfer a newly synthesized, anticancer platinum complex (bipyridine ethyl dithiocarbamate Pt(II) nitrate), to the colon. The effects of multiple factors on the size and the colloidal stability of the nanoparticles were studied using dynamic light scattering and scanning electron microscopy techniques. Results showed that the best particle size and highest colloidal stability were obtained in phosphate buffer, pH 4.5, with 0.5 mg/mL beta-lactoglobulin and 0.025-0.05wt% pectin. The drug release profile in simulated gastrointestinal conditions demonstrated that beta-lactoglobulin with a secondary coating is stable in acidic conditions but is able to release its cargo at pH 7. Hence, these nanoparticles have potential to serve as novel and effective vehicles for oral drug delivery preparations. PMID- 26896378 TI - Revisiting "The One-Minute Preceptor". PMID- 26896379 TI - Postexposure Management of Vaccine-Preventable Diseases. AB - Because some parents are choosing to not vaccinate or only partially vaccinate their children, vaccine-preventable diseases that once were rarely seen in pediatric practice must now be considered part of the differential diagnosis when caring for these children. Measles, mumps, varicella, meningococcal disease, pertussis, and influenza are reviewed. Recommendations for prevention and treatment of these vaccine-preventable diseases are discussed. PMID- 26896380 TI - [RECALMIN. Patient care in the internal medicine units of the Spanish national health system]. AB - OBJECTIVES: To perform a situation analysis of the care provided by internal medicine units (IMUs) in Spain and to develop, based on this analysis, proposals for improving the quality of care in these units. MATERIAL AND METHODS: A descriptive, cross-sectional study of the IMUs of general acute care hospitals of the Spanish National Health System (SNHS), with data referring to 2013. The study variables were collected via an ad hoc questionnaire. RESULTS: Of the total 260hospitals identified in the SNHS, 142responses were obtained from 139hospitals throughout Spain, which represents 53.5% of the IMUs in the SNHS. The mean number of internists per IMU was 14+/-8, with a mean rate of 7.2+/-3.3 internists per 100,000 inhabitants. In 2013, the average number of hospital discharges from the IMU was 2,987+/-2,066, and those discharged by internists was 232+/-107. Sixty one percent of the IMUs had implemented an interconsultation unit, and 41% had implemented a systematic care program for complex chronic patients. Thirty-three percent of the IMUs conducted multidisciplinary rounds, and 60% of these IMUs planned the discharge. CONCLUSIONS: The 2013 RECALMIN survey revealed a number of important aspects of the organisation, structure and management of IMUs. The remarkable variability in the indicators of structure, activity and management probably reflect significant differences in efficiency and productivity, which therefore provide significant room for improvement. PMID- 26896381 TI - Organ protection possibilities in acute heart failure. AB - Unlike chronic heart failure (HF), the treatment for acute HF has not changed over the last decade. The drugs employed have shown their ability to control symptoms but have not achieved organ protection or managed to reduce medium to long-term morbidity and mortality. Advances in our understanding of the pathophysiology of acute HF suggest that treatment should be directed not only towards correcting the haemodynamic disorders and achieving symptomatic relief but also towards preventing organ damage, thereby counteracting myocardial remodelling and cardiac and extracardiac disorders. Compounds that exert vasodilatory and anti-inflammatory action in the acute phase of HF and can stop cell death, thereby boosting repair mechanisms, could have an essential role in organ protection. PMID- 26896382 TI - Systematic Characterization of Long Noncoding RNAs Reveals the Contrasting Coordination of Cis- and Trans-Molecular Regulation in Human Fetal and Adult Hearts. AB - BACKGROUND: The molecular regulation of heart development is regulated by cis- and trans-factors acting on the genome and epigenome. As a class of important regulatory RNAs, the role of long noncoding RNAs (lncRNAs) in human heart development is still poorly understood. Furthermore, factors that interact with lncRNAs in this process are not well characterized. METHODS AND RESULTS: Using RNA sequencing, we systematically define the contrasting lncRNA expression patterns between fetal and adult hearts. We report that lncRNAs upregulated in adult versus fetal heart have different sequence features and distributions. For example, the adult heart expresses more sense lncRNAs compared with fetal heart. We also report the coexpression of lncRNAs and neighboring coding genes that have important functions in heart development. Importantly, the regulation of lncRNA expression during fetal to adult heart development seems to be due, in part, to the coordination of specific developmental epigenetic modifications, such as H3K4me1 and H3k4me3. The expression of promoter-associated lncRNAs in adult and fetal hearts also seems to be related to these epigenetic states. Finally, transcription factor-binding analysis suggests that lncRNAs are directly regulating cardiac gene expression during development. CONCLUSIONS: We provide a systematic analysis of lncRNA control of heart development that gives clues to the roles that specific lncRNAs play in fetal and adult hearts. PMID- 26896383 TI - Gene Expression Differences Between Offspring of Long-Lived Individuals and Controls in Candidate Longevity Regions: Evidence for PAPSS2 as a Longevity Gene. AB - Although there is compelling evidence for a genetic contribution to longevity, identification of specific genes that robustly associate with longevity has been a challenge. In order to identify longevity-enhancing genes, we measured differential gene expression between offspring of long-lived Amish (older than 90 years; cases, n = 128) and spouses of these offspring (controls, n = 121) and correlated differentially expressed transcripts with locations of longevity associated variants detected in a prior genome-wide association study (GWAS) of survival to age 90. Expression of one of these transcripts, 3'-phosphoadenosine 5'-phosphosulfate synthase 2 (PAPSS2), was significantly higher in offspring versus controls (4*10(-4)) and this association was replicated using quantitative real-time polymerase chain reaction. PAPSS2, a sulfation enzyme located on chromosome 10, is ~80kb upstream of the PAPSS2 transcription start site. We found evidence of cis-expression for the originally reported GWAS SNP and PAPSS2 Monogenic conditions linked to PAPSS2 include andrenocortical androgen excess resulting in premature pubarche and skeletal dysplasias, both of which have premature aging features. In summary, these findings provide novel evidence for PAPSS2 as a longevity locus and illustrate the value of harnessing multiple " omic" approaches to identify longevity candidates. PMID- 26896384 TI - Incidence of Atypical Femur Fractures in Cancer Patients: The MD Anderson Cancer Center Experience. AB - Atypical femoral fractures (AFFs) are rare adverse events attributed to bisphosphonate (BP) use. Few cases of AFF in cancer have been described; the aim of this study is to identify the incidence and risk factors for AFF in a large cancer center. This retrospective study was conducted at the MD Anderson Cancer Center. The incidence rate of AFF among BP users was calculated from January 1, 2004 through December 31, 2013. The control group (n = 51) included 2 or 3 patients on BPs matched for age (<=1 year) and gender. Logistic regression analysis was used to assess the relationship between clinical characteristics and AFF. Twenty-three AFF cases were identified radiographically among 10,587 BP users, the total BP exposure was 53,789 months (4482 years), and the incidence of AFF in BP users was 0.05 cases per 100,000 person-years. Meanwhile, among 300,553 patients who did not receive BPs there were 2 cases of AFF as compared with the 23 cases noted above. The odds ratio (OR) of having AFF in BP users was 355.58 times higher (95% CI, 84.1 to 1501.4, p < 0.0001) than the risk in non-BP users. The OR of having AFF in alendronate users was 5.54 times greater (OR 5.54 [95% CI, 1.60 to 19.112, p = 0.007]) than the odds of having AFF among other BP users. Patients who were on zoledronic acid (ZOL) had smaller odds of developing AFF compared with other BP users in this matched case control sample. AFFs are rare, serious adverse events that occur in patients with cancer who receive BP therapy. Patients with cancer who receive BPs for prior osteoporosis therapy or for metastatic cancer are at higher risk of AFF. (c) 2016 American Society for Bone and Mineral Research. PMID- 26896385 TI - Bi-ocularity, the functioning mind of the psychoanalyst. AB - With the use of clinical material the author discusses the importance of a 'bi ocular' mode of attentiveness, one pole of which rests on the psychic process of reverie and the other on 'analysing'. This is necessary to foster the development of a psychic space in which experiences which were 'in the shadow' or unrepresented, can come to the fore and be given shape first pictorially and later ideationally. This requires staying with and fostering the ambiguity of the different times and spaces without collapsing them into the clear, logical and explanatory. It requires the psychoanalyst to make space for that which is 'other', other than just apparently here and now, and other than just 'you and me', while maintaining the analytic 'fire' in a situation in which there is 'no model in real life', a place maximally geared to that which is not apparent. PMID- 26896386 TI - A possible venous connection between the cranial and nasal cavity. AB - PURPOSE: The foramen cecum (FC) is a fine bony canal with the aperture located immediately anterior to the crista galli (CG). The venous structures in the regions of the FC and CG have been inconsistently described and are not well understood. Here we explore these veins using magnetic resonance imaging. MATERIALS AND METHODS: We enrolled 101 patients who underwent contrast examinations and exhibited intact skin, skull, dura mater, and intracranial dural sinuses. Imaging data were obtained as thin-sliced, seamless sagittal sections and were transferred to a workstation for analysis. RESULTS: In 84 % of the patients, tubular-shaped venous extensions arose from the rostral end of the falx cerebri and were confirmed to lie in the FC. These extensions were supplied by the superior sagittal sinus or the frontal cortical vein, and were classified into four types: rudimental slight projections, short and straight extensions, long and straight channels, and long and tortuous channels. Furthermore, 27.7 % of the patients exhibited a distinct venous channel between the venous extension in the FC and the median vestibular submucosa of the nasal cavity. Among these channels, 81.5 % were connected to the vein lying in the FC via a short channel that vertically pierced the CG. CONCLUSIONS: The FC contains tubular-shaped venous extensions that are supplied by the rostral end of the superior sagittal sinus or the frontal cortical vein. The cranial cavity, FC, and nasal cavity may be connected by a venous channel. PMID- 26896387 TI - Determination of biodegradation rates for surfactants and a fatty alcohol in aerobic sediment using a simplified test system. AB - The development of specific regulatory persistence criteria and a growing need to conduct risk assessments in sediment have increased the need to better understand fate in this compartment. A simplified test approach was developed to assess the fate of chemicals in aerobic sediments and used to evaluate the biodegradation of (14) C-labeled representative analogs of alcohol sulfate, alcohol ethoxylate, alcohol ethoxy sulfate, linear alkylbenzene sulfonate, and tetradecanol in 2 different sediments. The method provides kinetic data on primary and ultimate biodegradation in sediments as well as information on biodegradation pathways and metabolites. All test materials exhibited extensive biodegradation in both sediments; disappearance of parent exhibited biphasic kinetics, described by a 2 compartment model, and mineralization was coupled to parent disappearance with little accumulation of metabolites. The first-compartment decay rates ranged from 10.8 d(-1) to 17.1 d(-1) for tetradecanol, 2.54 d(-1) to 24.8 d(-1) for alcohol sulfate, 0.17 d(-1) to 0.75 d(-1) for alcohol ethoxylate, 0.41 d(-1) to 0.71 d( 1) for alcohol ethoxy sulfate, and 0.26 d(-1) to 1.25 d(-1) for linear alkylbenzene sulfonate. These rates corresponded to half-lives ranging from 0.041 d to 4.08 d. This method's simplicity and focus on only sediment-associated processes offer potential benefits over the current Organisation for Economic Co operation and Development 308 aerobic sediment-water test. Environ Toxicol Chem 2016;35:2199-2208. (c) 2016 SETAC. PMID- 26896389 TI - Comparison of Survival and Osteogenic Ability of Human Mesenchymal Stem Cells in Orthotopic and Ectopic Sites in Mice. AB - Tissue constructs containing mesenchymal stem cells (MSCs) are appealing strategies for repairing large segmental bone defects, but they do not allow consistent bone healing and early cell death was identified as a cause of failure. However, little is known about cell survival in the clinical microenvironment encountered during bone healing process. Osteoconductive coral scaffold with or without luciferase-labeled human MSCs were implanted either in a critical segmental femoral bone defect stabilized by plate or subcutaneously in 44 mice. Cell survival was evaluated by serial bioluminescence imaging (BLI) and osteogenic capabilities by histology and microcomputed tomography. Comparisons between groups were performed with two-way analysis of variance test. Twenty mice were sacrificed 2 weeks after surgery for short-term evaluation and 24 mice at 10 weeks for long-term evaluation. BLI provided evidence of fast and continuous cell death: 85% decrease of the BLI signal over the first 2 weeks in both locations; in fact, less than 2% of the initial cell number was present in all constructs analyzed 4 weeks postimplantation and less than 1% of the initial cell number by 8 weeks postimplantation. By 2 weeks postimplantation, the amount of newly formed bone was self-limited and was similar to ectopic and orthotopic groups. By 10 weeks postimplantation, bone formation was significantly enhanced in the presence of MSCs in orthotopic site and the amount of newly formed bone in cell-containing constructs implanted in orthotopic locations was significantly higher than that observed in the ectopic group. Our results indicated that hMSCs promote bone formation despite early and massive cell death when loaded on coral scaffolds. Interestingly, bone formation was higher in orthotopic than ectopic site despite the same survival pattern. Ectopic implantation of cell-containing constructs is suitable to evaluate cell survival, but assessment of bone formation ability requires orthotopic implantation. PMID- 26896390 TI - Setup uncertainties in linear accelerator based stereotactic radiosurgery and a derivation of the corresponding setup margin for treatment planning. AB - PURPOSE: In the present study, clinical stereotactic radiosurgery (SRS) setup uncertainties from image-guidance data are analyzed, and the corresponding setup margin is estimated for treatment planning purposes. METHODS: Patients undergoing single-fraction SRS at our institution were localized using invasive head ring or non-invasive thermoplastic masks. Setup discrepancies were obtained from an in room x-ray patient position monitoring system. Post treatment re-planning using the measured setup errors was performed in order to estimate the individual target margins sufficient to compensate for the actual setup errors. The formula of setup margin for a general SRS patient population was derived by proposing a correlation between the three-dimensional setup error and the required minimal margin. RESULTS: Setup errors of 104 brain lesions were analyzed, in which 81 lesions were treated using an invasive head ring, and 23 were treated using non invasive masks. In the mask cases with image guidance, the translational setup uncertainties achieved the same level as those in the head ring cases. Re planning results showed that the margins for individual patients could be smaller than the clinical three-dimensional setup errors. The derivation of setup margin adequate to address the patient setup errors was demonstrated by using the arbitrary planning goal of treating 95% of the lesions with sufficient doses. CONCLUSIONS: With image guidance, the patient setup accuracy of mask cases can be comparable to that of invasive head rings. The SRS setup margin can be derived for a patient population with the proposed margin formula to compensate for the institution-specific setup errors. PMID- 26896388 TI - Healthy adolescent performance on the MATRICS Consensus Cognitive Battery (MCCB): Developmental data from two samples of volunteers. AB - The MATRICS Consensus Cognitive Battery (MCCB) fills a significant need for a standardized battery of cognitive tests to use in clinical trials for schizophrenia in adults aged 20-59. A need remains, however, to develop norms for younger individuals, who also show elevated risks for schizophrenia. Toward this end, we assessed performance in healthy adolescents. Baseline MCCB, reading and IQ data were obtained from healthy controls (ages 12-19) participating in two concurrent NIMH-funded studies: North American Prodromal Longitudinal Study phase 2 (NAPLS-2; n=126) and Boston Center for Intervention Development and Applied Research (CIDAR; n=13). All MCCB tests were administered except the Managing Emotions subtest from the Mayer-Salovey-Caruso Emotional Intelligence Test. Data were collected from 8 sites across North America. MCCB scores were presented in four 2-year age cohorts as T-scores for each test and cognitive domain, and analyzed for effects of age and sex. Due to IQ differences between age-grouped subsamples, IQ served as a covariate in analyses. Overall and sex-based raw scores for individual MCCB tests are presented for each age-based cohort. Adolescents generally showed improvement with age in most MCCB cognitive domains, with the clearest linear trends in Attention/Vigilance and Working Memory. These control data show that healthy adolescence is a dynamic period for cognitive development that is marked by substantial improvement in MCCB performance through the 12-19 age range. They also provide healthy comparison raw scores to facilitate clinical evaluations of adolescents, including those at risk for developing psychiatric disorders such as schizophrenia-related conditions. PMID- 26896391 TI - Floating on Air: Fulfillment and Self-in-Context for Distressed Japanese Women. AB - This research was part of a larger mixed-methods study examining culture, distress, and help seeking. We surveyed 209 Japanese women living in the United States recruited from clinic and community-based sites, and carried out semi structured ethnographic interviews with a highly distressed subsample of 25 Japanese. Analytic Ethnography revealed that women described themselves as a "self-in-context," negotiating situations using protective resources or experiencing risk exposure. Women experienced quality of life (QOL) when they were successful. However, a related goal of achievingIkigai(or purpose in life) was differentiated from QOL, and was defined as an ongoing process of searching for balance between achieving social and individual fulfillment. Our resulting hypothetical model suggested that symptom level would be related to risk and protective factors (tested for the full sample) and to specific risk and protective phenomenon (tested in the distressed subsample). Thettests in the full sample found that women who were above threshold for depressive symptoms (n= 26) had higher social stressor and lower social support means. Women who were above the threshold for physical symptoms (n= 99) had higher social stressor means. Analysis of the interviewed subsample found that low self-validation and excessive responsibilities were related to high physical symptoms. We conclude that perceived lack of balance between culturally defined, and potentially opposing, markers of success can create a stressful dilemma for first-generation immigrant Japanese women, requiring new skills to achieve balance. Perceptions of health, as well as illness, are part of complex culturally based interpretations that have implications for intervention for immigrant Japanese women living in the United States. PMID- 26896393 TI - Integration of Experiments across Diverse Environments Identifies the Genetic Determinants of Variation in Sorghum bicolor Seed Element Composition. AB - Seedling establishment and seed nutritional quality require the sequestration of sufficient element nutrients. The identification of genes and alleles that modify element content in the grains of cereals, including sorghum (Sorghum bicolor), is fundamental to developing breeding and selection methods aimed at increasing bioavailable element content and improving crop growth. We have developed a high throughput work flow for the simultaneous measurement of multiple elements in sorghum seeds. We measured seed element levels in the genotyped Sorghum Association Panel, representing all major cultivated sorghum races from diverse geographic and climatic regions, and mapped alleles contributing to seed element variation across three environments by genome-wide association. We observed significant phenotypic and genetic correlation between several elements across multiple years and diverse environments. The power of combining high-precision measurements with genome-wide association was demonstrated by implementing rank transformation and a multilocus mixed model to map alleles controlling 20 element traits, identifying 255 loci affecting the sorghum seed ionome. Sequence similarity to genes characterized in previous studies identified likely causative genes for the accumulation of zinc, manganese, nickel, calcium, and cadmium in sorghum seeds. In addition to strong candidates for these five elements, we provide a list of candidate loci for several other elements. Our approach enabled the identification of single-nucleotide polymorphisms in strong linkage disequilibrium with causative polymorphisms that can be evaluated in targeted selection strategies for plant breeding and improvement. PMID- 26896392 TI - Evx1 and Evx2 specify excitatory neurotransmitter fates and suppress inhibitory fates through a Pax2-independent mechanism. AB - BACKGROUND: For neurons to function correctly in neuronal circuitry they must utilize appropriate neurotransmitters. However, even though neurotransmitter specificity is one of the most important and defining properties of a neuron we still do not fully understand how neurotransmitter fates are specified during development. Most neuronal properties are determined by the transcription factors that neurons express as they start to differentiate. While we know a few transcription factors that specify the neurotransmitter fates of particular neurons, there are still many spinal neurons for which the transcription factors specifying this critical phenotype are unknown. Strikingly, all of the transcription factors that have been identified so far as specifying inhibitory fates in the spinal cord act through Pax2. Even Tlx1 and Tlx3, which specify the excitatory fates of dI3 and dI5 spinal neurons work at least in part by down regulating Pax2. METHODS: In this paper we use single and double mutant zebrafish embryos to identify the spinal cord functions of Evx1 and Evx2. RESULTS: We demonstrate that Evx1 and Evx2 are expressed by spinal cord V0v cells and we show that these cells develop into excitatory (glutamatergic) Commissural Ascending (CoSA) interneurons. In the absence of both Evx1 and Evx2, V0v cells still form and develop a CoSA morphology. However, they lose their excitatory fate and instead express markers of a glycinergic fate. Interestingly, they do not express Pax2, suggesting that they are acquiring their inhibitory fate through a novel Pax2-independent mechanism. CONCLUSIONS: Evx1 and Evx2 are required, partially redundantly, for spinal cord V0v cells to become excitatory (glutamatergic) interneurons. These results significantly increase our understanding of the mechanisms of neuronal specification and the genetic networks involved in these processes. PMID- 26896394 TI - Environmental Regulation of Heterosis in the Allopolyploid Arabidopsis suecica. AB - Allopolyploids are organisms possessing more than two complete sets of chromosomes from two or more species and are frequently more vigorous than their progenitors. To address the question why allopolyploids display hybrid vigor, we compared the natural allopolyploid Arabidopsis suecica to its progenitor species Arabidopsis thaliana and Arabidopsis arenosa. We measured chlorophyll content, CO2 assimilation, and carbohydrate production under varying light conditions and found that the allopolyploid assimilates more CO2 per unit chlorophyll than either of the two progenitor species in high intensity light. The increased carbon assimilation corresponds with greater starch accumulation, but only in strong light, suggesting that the strength of hybrid vigor is dependent on environmental conditions. In weaker light A. suecica tends to produce as much primary metabolites as the better progenitor. We found that gene expression of LIMIT DEXTRINASE1, a debranching enzyme that cleaves branch points within starch molecules, is at the same level in the allopolyploid as in the maternal progenitor A. thaliana and significantly more expressed than in the paternal progenitor A. arenosa. However, expression differences of beta-amylases and GLUCAN-WATER DIKINASE1 were not statistically significantly elevated in the allopolyploid over progenitor expression levels. In contrast to allopolyploids, autopolyploid A. thaliana showed the same photosynthetic rate as diploids, indicating that polyploidization alone is likely not the reason for enhanced vigor in the allopolyploid. Taken together, our data suggest that the magnitude of heterosis in A. suecica is environmentally regulated, arises from more efficient photosynthesis, and, under specific conditions, leads to greater starch accumulation than in its progenitor species. PMID- 26896395 TI - Herb Hydraulics: Inter- and Intraspecific Variation in Three Ranunculus Species. AB - The requirements of the water transport system of small herbaceous species differ considerably from those of woody species. Despite their ecological importance for many biomes, knowledge regarding herb hydraulics remains very limited. We compared key hydraulic features (vulnerability to drought-induced hydraulic decline, pressure-volume relations, onset of cellular damage, in situ variation of water potential, and stomatal conductance) of three Ranunculus species differing in their soil humidity preferences and ecological amplitude. All species were very vulnerable to water stress (50% reduction in whole-leaf hydraulic conductance [kleaf] at -0.2 to -0.8 MPa). In species with narrow ecological amplitude, the drought-exposed Ranunculus bulbosus was less vulnerable to desiccation (analyzed via loss of kleaf and turgor loss point) than the humid habitat Ranunculus lanuginosus Accordingly, water stress-exposed plants from the broad-amplitude Ranunculus acris revealed tendencies toward lower vulnerability to water stress (e.g. osmotic potential at full turgor, cell damage, and stomatal closure) than conspecific plants from the humid site. We show that small herbs can adjust to their habitat conditions on interspecific and intraspecific levels in various hydraulic parameters. The coordination of hydraulic thresholds (50% and 88% loss of kleaf, turgor loss point, and minimum in situ water potential) enabled the study species to avoid hydraulic failure and damage to living cells. Reversible recovery of hydraulic conductance, desiccation-tolerant seeds, or rhizomes may allow them to prioritize toward a more efficient but vulnerable water transport system while avoiding the severe effects that water stress poses on woody species. PMID- 26896397 TI - [Colombian Psychiatry: a Commitment for Everyone]. PMID- 26896398 TI - [Factors Related With Psychoactive Substance Use in an Educational Institution in Jamundi Valle, Colombia]. AB - OBJECTIVE: To estimate the prevalence of psychoactive substances (SPA) use in young people in an educational institution in Jamundi and possible related factors. METHODS: Cross-sectional study, analytical approach that simulates cases and controls, was conducted in an educational institution in Jamundi-Valley. The sample was composed of 146 students selected through simple random probability sampling without replacement. Participants individually and anonymously completed a questionnaire to identify SPA consumption and associated factors, including APGAR scale to measure family functioning. The data extracted from the questionnaires were entered into a matrix in Microsoft Excel and processed in EpiInfo version 5.0 and Stata. Descriptive analysis was performed, and a multivariate analysis was performed using unconditional logistic regression. RESULTS: Current consumption of SPA, 35%; age of first use was 10 to 13 years; the prevalence of drug misuse by gender was 34% for girls and 37% in boys. The most consumed legal substance was alcohol 34%, and illegal 3%. The most significant associations with the use of psychoactive substances was; having severe family dysfunction (OR=7.32; 95%CI, 1.74-30.76), being enrolled in the 11th grade (OR=14.6; 95%CI, 2.37-89.74), and having friends who use (OR=3.12; 95%CI, 2.49-10.38). CONCLUSIONS: The results obtained in this study show a high percentage of SPA consumption, with a higher prevalence in males. In this population, the most commonly used legal substance is alcohol. Family dysfunction and school grade were significantly associated with drug misuse. PMID- 26896396 TI - Lipid Droplet-Associated Proteins (LDAPs) Are Required for the Dynamic Regulation of Neutral Lipid Compartmentation in Plant Cells. AB - Eukaryotic cells compartmentalize neutral lipids into organelles called lipid droplets (LDs), and while much is known about the role of LDs in storing triacylglycerols in seeds, their biogenesis and function in nonseed tissues are poorly understood. Recently, we identified a class of plant-specific, lipid droplet-associated proteins (LDAPs) that are abundant components of LDs in nonseed cell types. Here, we characterized the three LDAPs in Arabidopsis (Arabidopsis thaliana) to gain insight to their targeting, assembly, and influence on LD function and dynamics. While all three LDAPs targeted specifically to the LD surface, truncation analysis of LDAP3 revealed that essentially the entire protein was required for LD localization. The association of LDAP3 with LDs was detergent sensitive, but the protein bound with similar affinity to synthetic liposomes of various phospholipid compositions, suggesting that other factors contributed to targeting specificity. Investigation of LD dynamics in leaves revealed that LD abundance was modulated during the diurnal cycle, and characterization of LDAP misexpression mutants indicated that all three LDAPs were important for this process. LD abundance was increased significantly during abiotic stress, and characterization of mutant lines revealed that LDAP1 and LDAP3 were required for the proper induction of LDs during heat and cold temperature stress, respectively. Furthermore, LDAP1 was required for proper neutral lipid compartmentalization and triacylglycerol degradation during postgerminative growth. Taken together, these studies reveal that LDAPs are required for the maintenance and regulation of LDs in plant cells and perform nonredundant functions in various physiological contexts, including stress response and postgerminative growth. PMID- 26896399 TI - [Comparison of Inflammatory Biomarkers Between Bipolar Disorder I Patients and Control Subjects]. AB - INTRODUCTION: Inflammatory changes have been described in different affective episodes, as well as in the euthymic phase of Bipolar I Disease. These changes have been proposed as possible peripheral markers of the disease. For this reason well-designed studies are needed to explore this hypothesis. OBJECTIVE: Quantify and compare the serum levels of interleukins (IL) and tumour necrosis factor (TNF) in bipolar I patients and healthy subjects, including the comparison between the affective episodes of the disease. METHODS: Cross-sectional study including 41 bipolar I patients and 11 healthy control subjects. Serum levels of IL-1B, IL-RA, IL-2, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12, and TNF were measured during the euthymic, depressive, and manic phases and were compared with the serum levels of the healthy subjects. CONCLUSIONS: Manic phase patients had low education and high number of hospitalisations. Depressive phase patients showed high number of depressive episodes throughout life. No statistically significant differences were found in IL and TNF levels between bipolar I patients and healthy controls, or between the bipolar I subgroups (euthymic, manic and depressive states). An increase in the size of the sample is necessary in future studies, in order to enhance the statistical value of the results, and explore the inflammatory hypothesis of the bipolar disease. PMID- 26896400 TI - [Not Available]. AB - OBJECTIVE: To analyse sociodemographic characteristics, descriptive psychopathology and therapy in the first decade of service of the Hospital Psiquiatrico San Isidro del Valle del Cauca, 1958-1968. METHODOLOGY: Retrospective descriptive study of a series of case histories of the studied period, and by qualitative analysis and conceptual networks. RESULTS: Sociodemographic variables were analysed, and it was observed that, although the patient population increased, hospitalisation was reduced due to the implementation of a "Day Hospital" and outpatient services. The majority of patients were young adults, women engaged in housework, and several lower-middle income patients, primarily referred by their families. Hospital stay was short, with a high frequency of readmissions. The main reason for discharge was improvement, and the predominant diagnosis and symptomatology was schizophrenia, with the treatment being antipsychotic neuroleptics. CONCLUSIONS: The correlation of the short time of hospitalisation, more outpatient clinics, the large number of readmissions, and improvement as the reason for discharge, is consistent with the results of the International Pilot Study of Schizophrenia 1968, which included a sample of 100 patients from Hospital psychiatric San Isidro del Valle del Cauca, in which it was concluded that the disorder did not cause a progressive deterioration in patients and that, on the contrary, showed a significant percentage recovery. PMID- 26896401 TI - [Sensitivity and specificity between the Composite International Diagnostic Interview Version 3.0 (World Mental Health, CIDI) and the Standardised Clinical Evaluation version I (SCID-I) in a mental health survey of the city of Medellin, 2012]. AB - INTRODUCTION: In order to address the mental health problems of the Colombian population it is necessary to have diagnostic tools (local and international) that are valid, easy to apply, and comparable. OBJECTIVE: To compare the sensitivity and specificity between the CIDI 3.0 and the SCID-I for major depressive disorder, bipolar I and II disorder, and substance dependence disorder. METHODOLOGY: Cross-sectional study comparing the life prevalence of three mental disorders in 100 subjects using the CIDI 3.0 and the SCID-I. The study was approved by the Institutional Ethics Committee. The two diagnostic interviews were performed that measured by sensitivity, specificity, positive predictive value and negative predictive value with confidence intervals of 95%. The SPSS version 21.0 software was used for data analysis. RESULTS: The median age was 43.5 years, with an interquartile interval of 30 years. The highest sensitivity (Se) and specificity (Sp) was observed for drug dependence diagnosis with 80%, (95%CI, 34.94-100), and 98.46 (95%CI, 94.7-100), respectively. CONCLUSIONS: SCID-I and CIDI 3.0 showed different levels of sensitivity and specificity for the three disorders studied with: high for substance dependence disorder, moderate for bipolar disorder I and II, and low for major depressive disorder. PMID- 26896402 TI - [Psychiatric, Cognitive and Emotional Profile in Ex-combatants of Illegal Armed Groups in Colombia]. AB - INTRODUCTION: Exposure to armed conflict produces biological adaptations oriented to handle the highly stressful conditions in war environments. The special features of The Colombian armed create a special scenario to evaluate the human behavior. OBJECTIVE: In this study, psychiatric, cognitive and emotional processing characteristics of a group of Colombian armed illegal forces of ex combatants are described. METHODS: Sixty-three ex combatants and 22 controls were assessed with WAIS (IQ), INECO frontal screening (executive functions), Interpersonal Reactivity Index (empathy), emotional features recognition and MINI (psychiatric profile). RESULTS: When compared to the control group, ex-combatants showed higher frequency of antisocial personality disorder (P=.031) and behavioral dissocial disorder (P=.017). In cognitive profile, the ex-combatants showed a lower score in the executive function test (Me=18.50; RQ=4.00), control (Me=23.00; RQ=5.25), with a poor personal distress in emphatic profile (Me=10.00; RQ=5.00) compared to control group (Me=37.00; RQ=7.25). CONCLUSIONS: We found differences in cognitive and psychiatric profile in ex-combatants in comparison with controls. PMID- 26896403 TI - [Delirium Prevention]. AB - INTRODUCTION: Delirium is the most prevalent neuropsychiatric syndrome in the general hospital. Its presence is a marker of poor prognosis for patients. Its prevention could be the most effective strategy for reducing its frequency and its complications. OBJECTIVE: To review recent findings and strategies for the prevention of delirium. METHODOLOGY: A non-systematic review of scientific articles published in the last ten years in Spanish and English. A search was made in databases such as MEDLINE, Cochrane, EMBASE, Ovid, and ScienceDirect, for articles that included the terms, delirium and prevention. RESULTS: Identification of predisposing and precipitating factors for delirium and a better understanding of the pathophysiological mechanisms underlying the onset of delirium have enabled the implementation of various pharmacological and non pharmacological strategies in patients at high risk to develop hospital delirium. The studies to prevent delirium have focused on surgical patients. The current evidence supports the daily implementation of non-pharmacological measures to prevent delirium, as they are easy and cost effective. The available evidence is still limited to recommend the daily use of pharmacological strategies in delirium prophylaxis, and there is a consensus against the modest use of antipsychotic drugs in surgical patients and dexmedetomidine in patients in intensive care. CONCLUSIONS: New high-quality clinical trials and studies involving non-surgical patients are needed to provide more evidence about this subject. PMID- 26896404 TI - [Intervention of Schizophrenia From the Community Model]. AB - INTRODUCTION: Schizophrenia is a complex disease for which pharmacological management is an insufficient therapeutic measure to ensure adaptation to the community and restoring the quality of life of the patient, with a multidimensional management and community interventions being necessary. METHODOLOGY: Case report. RESULTS: This case report illustrates a multidisciplinary treatment response, based on a community care model for mental health from Envigado, Colombia. DISCUSSION: The management of schizophrenia requires multimodal interventions that include community screening, psychoeducation of individuals, their families and society, addressing different areas of operation that allow adaptation of the subject to his social environment. CONCLUSIONS: A integrated intervention that can be provided on a Community scale, with the implementation of policies that allow it to be applied. PMID- 26896405 TI - [Child sexual abuse: clinical perspectives and ethico-legal dilemmas]. AB - OBJECTIVES: In the review of the current literature, the main causing factors of the related conditions with child sexual abuse are the ethical dilemmas and legal implications. METHODS: A review was conducted on the classic literature on this topic. In this articlesome difficult paradigmatic cases are presented in which the hypothetical dilemmas were solved. RESULTS: The main characteristics of child sexual abuse enable us to have a better argument to address these situations. CONCLUSIONS: Taking into account the literature reviewed and predictable courses of action, it is concluded that it is important to take into account each individual each case and its circumstances, and that prudence and clinical objectivity, as well as knowledge of the law, become essential requirements for proper action. PMID- 26896408 TI - Influence of experience on intra- and inter-observer reproducibility of the Crowe, Hartofilakidis and modified Cochin classifications. AB - INTRODUCTION: A previous study demonstrated that the reproducibility of the Crowe (Cr), the Hartofilakidis (Ha) and the modified Cochin (Co) classifications were comparable. However, there were differences with a trend that suggested the influence of experience. Therefore, we performed a prospective study to investigate whether experience influenced the reproducibility of the commonly used developmental dysplasia of the hip (DDH) classifications. HYPOTHESIS: The hypothesis was that the intra- and inter-observer reproducibility scores would be higher in the senior group than the junior group, and particularly for the modified Co classification. METHODS: Four seniors and four residents classified 104 A/P pelvic radiographs (200 hips) two times using the Cr, Ha and Co classification systems. RESULTS: For intra-observer reproducibility, the average weighted concordance coefficients [95% confidence intervals] were for the senior and the junior groups: 92.2 [88.6-95.7] and 92.6 [87.9-97.2] for Cr, 92.1 [88.7 94.6] and 92.0 [87.7-96.3] for Ha, 94.2 [91.8-96.6] and 94.1 [91.5-96.6] for Co. The average weighted Kappa (95% confidence intervals) were 0.8 [0.71-0.88] and 0.79 [0.68-0.89] for Cr, 0.77 [0.74-0.81] and 0.75 [0.62-0.88] for Ha, 0.82 [0.76 0.89] and 0.80 [0.74-0.87] for Co. The junior inter-observer reproducibility multi-rater Kappa (list A:list B) were 0.57:0.50 (Cr), 0.47:0.53 (Ha), 0.42:0.42 (Co). Senior multi-rater Kappa were 0.53:0.49 (Cr), 0.40:0.34 (Ha), 0.40:0.43 (Co). CONCLUSIONS: Contrary to our hypothesis, the experience of the observer did not affect the intra- and inter-observer reproducibility of the three classification systems. PMID- 26896406 TI - The Cumulative Lifting Index (CULI) for the Revised NIOSH Lifting Equation: Quantifying Risk for Workers With Job Rotation. AB - OBJECTIVE: The objectives were to: (a) develop a continuous frequency multiplier (FM) for the Revised NIOSH Lifting Equation (RNLE) as a function of lifting frequency and duration of a lifting task, and (b) describe the Cumulative Lifting Index (CULI), a methodology for estimating physical exposure to workers with job rotation. BACKGROUND: The existing FM for the RNLE (FME) does not differentiate between task duration >2 hr and <8 hr, which makes quantifying physical exposure to workers with job rotation difficult and presents challenges to job designers. METHOD: Using the existing FMs for 1, 2, and 8 hr of task durations, we developed a continuous FM (FMP) that extends to 12 hr per day. We simulated 157,500 jobs consisting of two tasks each and, using different combinations of Frequency Independent Lifting Index, lifting frequency and duration of lifting. Biomechanical stresses were estimated using the CULI, time-weighted average (TWA), and peak exposure. RESULTS: The median difference between FME and FMP was +/-1% (range: 0%-15%). Compared to CULI, TWA underestimated risk of low-back pain (LBP) for 18% to 30% of jobs, and peak exposure for an assumed 8-hr work shift overestimated risk of LBP for 20% to 25% of jobs. Peak task exposure showed 90% agreement with CULI but ignored one of two tasks. CONCLUSION: The CULI partially addressed the underestimation of physical exposure using the TWA approach and overestimation of exposure using the peak-exposure approach. APPLICATION: The proposed FM and CULI may provide more accurate physical exposure estimates, and therefore estimated risk of LBP, for workers with job rotation. PMID- 26896409 TI - Mosaicplasty for femoral osteochondritis dissecans. AB - The authors describe a surgical mosaicplasty technique, with an anterior surgical dislocation approach without trochanterotomy, for osteochondritis dissecans of the hip. A graft was taken from the lateral condyle of the knee. Two adolescents underwent this procedure with good results. No osteonecrosis was observed at the longest follow-up. Mosaicplasty is a useful treatment method for small osteochondritis dissecans (<2cm(2)). PMID- 26896410 TI - Short medial approach harvesting of hamstring tendons. AB - Harvesting the hamstring tendons for anterior cruciate ligament reconstruction is not straightforward to perform or to teach: the incision is small, the work-space is narrow and the surgeon's tactile feedback using the stripper is difficult to explain to juniors. The purpose of this short note is to describe a reliable means of harvesting the semitendinosus, gracilis or both. Patient and tourniquet positioning, instrumentation and landmarks are detailed; then the 6 steps (speed bump 1, speed-bump 2, bubble, hook, expansions, stripper) are explained. PMID- 26896411 TI - Results with all-inside meniscal suture in pediatrics. AB - INTRODUCTION: Incidence of meniscal lesions is increasing in the pediatric population. Given the harmful impact of meniscectomy, meniscal repair is attempted whenever possible. The present study sought to assess the efficacy of FasT-Fix (Smith and Nephew) all-inside arthroscopic meniscal repair devices in childhood meniscal lesions. The study hypothesis was that functional results would be equivalent to those of other suture techniques. MATERIAL AND METHODS: Nineteen patients were assessed following arthroscopic meniscal repair, at a mean 6 years (range: 3-9 years). Mean age was 14.8 years. There was associated ACL tear in 31% of cases. Functional assessment used Lysholm, subjective IKDC, Tegner activity level and KOOS scores. Anatomic assessment of healing used MRI, arthroscopy or CT-arthrography. RESULTS: At last follow-up, the meniscal survival rate was 89.5% (n=17/19). Functional results were good: Lysholm: 95.7/100; subjective IKDC: 90.7/100; Tegner: 7.64. Imaging found systematic healing. DISCUSSION: All-inside arthroscopic meniscal suture is increasingly used in adults, and can also be implemented in children or adolescents in pediatrics. FasT-Fix (Smith and Nephew) implants, although not always easy to use, ensure a perfectly functional knee and conserve long-term meniscal chondroprotection with a low risk of complications. LEVEL OF EVIDENCE: IV, retrospective study. PMID- 26896412 TI - Shoulder arthroscopy and ATAK (adrenaline, Takotsubo, anaphylaxis, and Kounis hypersensitivty-associated syndrome). PMID- 26896415 TI - Pancoronary instability: the vulnerable patient revisited? PMID- 26896413 TI - Systolic hypertension and progression of aortic valve calcification in patients with aortic stenosis: results from the PROGRESSA study. AB - AIMS: Hypertension is highly prevalent in patients with aortic stenosis (AS) and is associated with worse outcomes. The current prospective study assessed the impact of systolic hypertension (SHPT) on the progression of aortic valve calcification (AVC) measured by multidetector computed tomography (MDCT) in patients with AS. METHODS AND RESULTS: The present analysis includes the first series of 101 patients with AS prospectively recruited in the PROGRESSA study. Patients underwent comprehensive Doppler echocardiography and MDCT exams at baseline and after 2-year follow-up. AVC and coronary artery calcification (CAC) were measured using the Agatston method. Patients with SHPT at baseline (i.e. systolic blood pressure >=140 mmHg; n = 37, 37%) had faster 2-year AVC progression compared with those without SHPT (i.e. systolic blood pressure <140 mmHg) (AVC median [25th percentile-75th percentile]: +370 [126-824] vs. +157 [58 303] AU; P = 0.007, respectively). Similar results were obtained with the analysis of AVC progression divided by the cross-sectional area of the aortic annulus (AVCdensity: +96 [34-218] vs. +45 [14-82] AU/cm2, P = 0.01, respectively). In multivariable analysis, SHPT remained significantly associated with faster progression of AVC or AVCdensity (all P = 0.001). There was no significant difference between groups with respect to progression of CAC (+39 [3 199] vs. +41 [0-156] AU, P = 0.88). CONCLUSION: This prospective study shows for the first time that SHPT is associated with faster AVC progression but not with CAC progression in AS patients. These findings provide further support for the elaboration of randomized clinical trials to assess the efficacy of antihypertensive medication to slow the stenosis progression in patients with AS. PMID- 26896414 TI - Ratio of transmitral early filling velocity to early diastolic strain rate predicts outcomes in patients with systolic heart failure. AB - AIMS: The ratio of transmitral early filling velocity (E) to early diastolic tissue velocity (E') is a key diastolic function parameter. The early diastolic strain rate (E'sr) has been proposed as a substitute for E' in the E/E' ratio for better estimation of left ventricular (LV) filling pressure. This study aims to assess the predictive value of combined E/E'sr ratio and global longitudinal strain (GLS) for prognosis in systolic heart failure (SHF). METHODS AND RESULTS: We retrospectively analysed 330 SHF patients with an LV ejection fraction (LVEF) <= 40%. Study end points were defined as all-cause mortality or heart transplantation. The incremental value of GLS and the E/E'sr ratio over LVEF and E/E' for outcome prediction was assessed using nested Cox models. Ninety-nine (30%) patients reached the end point over a median follow-up of 46 months. Baseline variables associated with outcomes were age, glomerular filtration rate, pulmonary artery systolic pressure, and LV end-systolic volume index. After multivariate adjustment, GLS (hazard ratio: 1.48, P = 0.025) and the E/E'sr ratio (hazard ratio: 1.41, P = 0.002) were both independent predictors. LVEF or E/E' was not an independent predictor when GLS and E/E'sr were included in the model. Patients with impaired GLS (absolute value <7.5%) and elevated E/E'sr ratios (E/E'sr >= 195 cm) showed poor outcomes. CONCLUSION: The E/E'sr ratio is stronger than E/E' ratio in predicting prognosis of patients with systolic HF. Combined assessments of GLS and E/E'sr by speckle-tracking longitudinal strain facilitate risk stratification of these patients. PMID- 26896416 TI - The Nanophysiology of Fast Transmitter Release. AB - Action potentials invading the presynaptic terminal trigger discharge of docked synaptic vesicles (SVs) by opening voltage-dependent calcium channels (CaVs) and admitting calcium ions (Ca(2+)), which diffuse to, and activate, SV sensors. At most synapses, SV sensors and CaVs are sufficiently close that release is gated by individual CaV Ca(2+) nanodomains centered on the channel mouth. Other synapses gate SV release with extensive Ca(2+) microdomains summed from many, more distant CaVs. We review the experimental preparations, theories, and methods that provided principles of release nanophysiology and highlight expansion of the field into synaptic diversity and modifications of release gating for specific synaptic demands. Specializations in domain gating may adapt the terminal for roles in development, transmission of rapid impulse frequencies, and modulation of synaptic strength. PMID- 26896417 TI - Carbon Dioxide Flushing Technique to Prevent Cerebral Arterial Air Embolism and Stroke During TEVAR. AB - PURPOSE: To describe the technique of carbon dioxide (CO2) flushing of thoracic stent-grafts to reduce the risk of cerebral air embolism. TECHNIQUE: To remove room air, thoracic stent-grafts were preoperatively flushed 2 minutes with carbon dioxide from a cylinder connected to the flushing chamber of the captor valves of Zenith custom-made endografts; this was followed by the standard saline flush. Thirty-six patients undergoing thoracic endovascular aortic repairs (TEVAR) involving the ascending aorta and the aortic arch received CO2-flushed Zenith endografts. One patient with a highly calcified arch experienced a minor stroke. CONCLUSION: Arterial air embolism is a potentially underappreciated problem of aortic endografting, especially in the proximal segments of the aorta. CO2 flushing may have the potential to reduce air embolization during TEVAR. PMID- 26896418 TI - Sense of Competence Impedes Uptake of New Academy Evidence-Based Practice Guidelines: Results of a Survey. PMID- 26896419 TI - Disordered eating and the contradictions of neoliberal governance. AB - The last decade has seen the development of an important literature on the contradictions between neoliberal norms of corporal citizenship and the forms of consumption that market-based food systems promote. This paper seeks to contribute to the literature by exploring the relationship between these contradictions and the increased prevalence of particular eating disorders (binge eating disorder (BED) and bulimia nervosa). Within contemporary neoliberal food systems bingeing is increasingly normalised and consumption temporally disorganised. At the same time, neoliberal public health policy, and the wider 'health' entertainment media it legitimates, focuses on the promotion of 'correct' forms of consumer agency. Individuals who fail to manage consumption 'appropriately' are stigmatised. The growth of bulimia and BED can be related to the contradictory pressures that the food system and regime of corporal governance place on individuals. The paper also seeks to explore how the increased medicalisation and biomedicalisation of eating since the 1980s fits within a broader neoliberal governance strategy. By medicalising key social problems the neoliberal state depoliticises these issues. Medicalisation and biomedicalisation obscure the role of capitalism in generating these problems and encourage a focus on individual dysfunction. PMID- 26896421 TI - Commentary on 'Metapsychological and clinical issues in psychosomatics research' by Jacques Press. PMID- 26896420 TI - Glycolipid-based TLR4 Modulators and Fluorescent Probes: Rational Design, Synthesis, and Biological Properties. AB - The cationic glycolipid IAXO-102, a potent TLR4 antagonist targeting both MD-2 and CD14 co-receptors, has been used as scaffold to design new potential TLR4 modulators and fluorescent labels for the TLR4 receptor complex (membrane TLR4.MD 2 dimer and CD14). The primary amino group of IAXO-102, not involved in direct interaction with MD-2 and CD14 receptors, has been exploited to covalently attach a fluorescein (molecules 1 and 2) or to link two molecules of IAXO-102 through diamine and diammonium spacers, obtaining 'dimeric' molecules 3 and 4. The structure-based rational design of compounds 1-4 was guided by the optimization of MD-2 and CD14 binding. Compounds 1 and 2 inhibited TLR4 activation, in a concentration-dependent manner, and signaling in HEK-Blue TLR4 cells. The fluorescent labeling of murine macrophages by molecule 1 was inhibited by LPS and was also abrogated when cell surface proteins were digested by trypsin, thus suggesting an interaction of fluorescent probe 1 with membrane proteins of the TLR4 receptor system. PMID- 26896422 TI - Addition of lafutidine can improve disease activity and lead to better quality of life in refractory cholinergic urticaria unresponsive to histamine H1 antagonists. PMID- 26896423 TI - Evidence for Different Trajectories of Delay Discounting in Older Adults With Mild Cognitive Impairment and Mild Alzheimer's Disease. AB - Objectives: To examine whether delay discounting (DD) develops differently within individuals diagnosed with mild cognitive impairment (MCI) or mild Alzheimer's disease (AD). Method: We set out to study trajectories of DD in N = 111 older adults (Mage = 75.2 years, range: 55-94, 53% female) with MCI (n = 64) or mild AD (n = 47). Data were repeatedly assessed on three measurement times over a period of 2 years. Results: Results indicated a meaningful difference in the trajectories of DD between MCI and mild AD (t = 2.99, p = .004), with AD patients displaying higher DD rates compared with MCI. Lower intelligence (t = -2.50, p = .013) was related to higher DD. We also found reward-dependent group differences in DD (small: p = .079; medium: p = .258; large: p = .007). Age, functional ability, general cognitive ability, living situation, and marital status were not meaningfully linked to DD (all non significant). Further explorative analyses revealed an increase in DD in patients whose cognitive symptoms had progressed at time 2, compared with more stable courses of mild AD or MCI (diagnosed at time 2). Discussion: Our results point toward an increase in DD as a function of advanced cognitive decline. PMID- 26896424 TI - An Endochondral Ossification-Based Approach to Bone Repair: Chondrogenically Primed Mesenchymal Stem Cell-Laden Scaffolds Support Greater Repair of Critical Sized Cranial Defects Than Osteogenically Stimulated Constructs In Vivo. AB - The lack of success associated with the use of bone grafts has motivated the development of tissue engineering approaches for bone defect repair. However, the traditional tissue engineering approach of direct osteogenesis, mimicking the process of intramembranous ossification (IMO), leads to poor vascularization. In this study, we speculate that mimicking an endochondral ossification (ECO) approach may offer a solution by harnessing the potential of hypertrophic chondrocytes to secrete angiogenic signals that support vasculogenesis and enhance bone repair. We hypothesized that stimulation of mesenchymal stem cell (MSC) chondrogenesis and subsequent hypertrophy within collagen-based scaffolds would lead to improved vascularization and bone formation when implanted within a critical-sized bone defect in vivo. To produce ECO-based constructs, two distinct scaffolds, collagen-hyaluronic acid (CHyA) and collagen-hydroxyapatite (CHA), with proven potential for cartilage and bone repair, respectively, were cultured with MSCs initially in the presence of chondrogenic factors and subsequently supplemented with hypertrophic factors. To produce IMO-based constructs, CHA scaffolds were cultured with MSCs in the presence of osteogenic factors. These constructs were subsequently implanted into 7 mm calvarial defects on Fischer male rats for up to 8 weeks in vivo. The results demonstrated that IMO- and ECO based constructs were capable of supporting enhanced bone repair compared to empty defects. However, it was clear that the scaffolds, which were previously shown to support the greatest cartilage formation in vitro (CHyA), led to the highest new bone formation (p < 0.05) within critical-sized bone defects 8 weeks postimplantation. We speculate this to be associated with the secretion of angiogenic signals as demonstrated by the higher VEGF protein production in the ECO-based constructs before implantation leading to the greater blood vessel ingrowth. This study thus demonstrates the ability of recapitulating a developmental process of bone formation to develop tissue-engineered constructs that manifest appreciable promise for bone defect repair. PMID- 26896425 TI - Letter by Chugh and Chugh Regarding Article, "Comparison of Right and Left Upper Limb Arterial Variants in Patients Undergoing Bilateral Transradial Procedures". PMID- 26896426 TI - [Obstetrical vesico-vaginal fistula in Guinea: Data analysis of three sites of treatment at Engender Health ONG]. AB - OBJECTIVE: To analyze the management of obstetric vesico-vaginal fistula in the three sites of Engender Health in Guinea. PATIENTS AND METHODS: It was a retrospective study of descriptive type having helped collect 450 cases of vesico vaginal fistulas in three support sites engender health between January 2008 and December 2011. The variables studied were epidemiological, clinical and therapeutic reasons and treatment outcomes were evaluated after a decline of at least six months. RESULTS: The mean age of onset of the fistula was 25years, ranging from 12 to 55years and 58.8% (n=265) of patients were aged between 18 and 30years. The mean duration of fistula was 11years, ranging from 1 to 38years. Eighty-two percent (n=416) of patients were housewives and 66.4% (n=299) off school. The complex fistula with 66% (n=297) was the most frequent. The treatment consisted of a fistulorraphie after splitting vesico-vaginal in 93.3% (n=420) of cases. Therapeutic results considered after a mean of 8months have resulted in a cure in 79.3% (n=357) of cases, improvement in 4.2% (n=19) of cases and failure in 16 4% (n=74) of cases. CONCLUSION: Vesico-vaginal fistula is a major cause of maternal morbidity in Guinea. The establishment of a real health policy based on sound medical and social structures contributes to its eradication. LEVEL OF EVIDENCE: 5. PMID- 26896427 TI - [Mechanisms of castration resistance: Intratumoral hypoxia stimulates the androgen receptor expression]. AB - PURPOSE: Tumor hypoxia and its biological consequence lead to microenvironment adaptation of tumor initiation, promotion and progression. The aim of the study was to observe the influence of hypoxia on the expression of the androgen receptor (AR), using an original model of multicellular spheroids obtained from castration-resistant prostate tumor cells. MATERIAL: Two human castration resistant prostate cancer cell lines have been used to generate multicellular tumor spheroids (MTS). The conditions and duration of incubation modulated the final size of the MTS and the intrinsic hypoxia gradient. The expression of AR was studied by immunohistochemistry (IHC) and secretion of PSA measured in the culture medium. RESULTS: The IHC expression of AR was characterized by a decreasing gradient from the periphery to the center of MTS (less intense in central hypoxic zone), corresponding to a nuclear translocation of activated AR. This result was proportionally correlated with the duration of hypoxic incubation period. Hypoxia caused significant increase in AR expression at 6h of oxygen deprivation. This activation of AR was correlated with transcriptional activity increase of target genes, including increased secretion of PSA. CONCLUSION: This demonstration of activation, increased expression and increased transcriptional activity of AR by hypoxia is the first to have been made with an original model of hypoxia, closer to reality than previous models, i.e. close to tissue hypoxia observed in primary prostate cancer. LEVEL OF EVIDENCE: 4. PMID- 26896428 TI - Comparative speed of kill of sarolaner (Simparica) and afoxolaner (NexGard) against induced infestations of Ctenocephalides felis on dogs. AB - BACKGROUND: Fleas are the most common ectoparasite infesting dogs globally. The many possible sequellae of infestation include: direct discomfort; allergic reactions; and the transmission of pathogens. Rapid speed of kill is an important characteristic for a parasiticide in order to alleviate the direct deleterious effects of fleas, reduce the impact of allergic responses, and break the flea infestation cycle. In this study, the speed of kill of a novel orally administered isoxazoline parasiticide, sarolaner (Simparica) against fleas on dogs was evaluated and compared with afoxolaner (NexGard) for 5 weeks after a single oral dose. METHODS: Twenty-four dogs were randomly allocated to treatment with a single oral dose at label rate of either sarolaner (2 to 4 mg/kg) or afoxolaner (2.5 to 6.8 mg/kg) or placebo, based on pretreatment flea counts. Dogs were combed and live fleas counted at 8, 12 and 24 h after treatment and subsequent re-infestations on Days 7, 14, 21, 28 and 35. Efficacy was determined at each time point relative to counts for placebo dogs. RESULTS: There were no adverse reactions to treatment. A single oral dose of sarolaner provided >=98.8% efficacy (based on geometric means) within 8 h of treatment or subsequent weekly re-infestations of fleas to Day 35. By 12 h, fleas were virtually eradicated from all dogs, with only two fleas recovered from a single sarolaner-treated dog on Day 7; efficacy was 100% at all other time points. Significantly greater numbers of live fleas were recovered from afoxolaner-treated dogs at 8 h on all days and at 12 h on Days 28 and 35 (P < 0.05). CONCLUSIONS: In this controlled laboratory evaluation, sarolaner had a significantly faster speed of kill against fleas than afoxolaner. This was noticeably more evident towards the end of the treatment period. The rapid and consistent kill of fleas within 8 to 12 h after a single oral dose of sarolaner over 35 days indicates that this treatment will provide highly effective control of flea infestations, relief for dogs afflicted with flea allergy dermatitis, and should reduce the risk of flea-borne pathogen transmission. PMID- 26896429 TI - HOXA10, EMX2 and TENM1 expression in the mid-secretory endometrium of infertile women with a Mullerian duct anomaly. AB - Homeobox A10 (HOXA10) and empty spiracles homeobox 2 (EMX2) are two transcription factors necessary for female Mullerian duct differentiation and development. They are thought to play important roles in embryo implantation in mice and humans. The EMX2 gene is a known direct target of HOXA10 in the reproductive tract. Human TENM1 is directly regulated by EMX2 and is expressed during embryonic pattern formation and morphogenesis. This study aimed to investigate expression patterns of HOXA10, EMX2 and TENM1 in the mid-secretory endometrium of infertile patients with a Mullerian duct anomaly causing a partially septate uterus. Thirteen mid secretory endometrial tissue samples were collected from women with partially septate uteri and 12 from women with normal uteri as controls. Expression levels of HOXA10, EMX2 and TENM1 mRNA and protein in the mid-secretory endometrium of infertile patients and controls were measured by quantitative reverse transcription polymerase chain reaction and western blotting. Compared with controls, mRNA and protein expression levels of HOXA10 decreased significantly (P < 0.01), whereas EMX2 and TENM1 increased dramatically in patients with Mullerian duct anomaly (P < 0.001). Changes in HOXA10, EMX2, and TENM1 expression levels might act in infertile women with Mullerian duct anomaly to cause a partially septate uterus. PMID- 26896430 TI - The role of in-vivo and in-vitro maturation time on ooplasmic dysmaturity. AB - This study investigates whether the timing of in-vivo and in-vitro maturation influences ooplasmic dysmaturity. This is a retrospective comparison of intracytoplasmic sperm injection (ICSI) cycles (index cycles) complicated by complete fertilization failure (CFF) to cycles with successful fertilization in the same patient. The cycle following the index cycle was modified intentionally to increase fertilization. The times between human chorionic gonadotrophin (HCG) trigger and oocyte retrieval, HCG trigger and removal of cumulus cells, and HCG trigger and sperm injection were recorded. Fifteen patients were included. Compared with successful fertilization cycles, index (CFF) cycles showed a shorter time interval between HCG trigger and oocyte retrieval (2029.0 +/- 16 versus 2195.0 +/- 10 min; P < 0.001), HCG trigger and removal of cumulus cells (2201.4 +/- 15 versus 2309.0 +/- 23 min; P < 0.001) and oocyte retrieval and removal of cumulus cells (114.0 +/- 13 versus 171.8 +/- 15 min; P < 0.001). The interval between HCG trigger and ICSI was comparable between groups. Findings reveal novel patterns in time intervals between HCG trigger, oocyte retrieval, removal of cumulus cells and ICSI. Thus, modulating time intervals between HCG trigger, oocyte retrieval, removal of cumulus cells and ICSI to grant fertilization seems feasible. PMID- 26896431 TI - Calcium gets myosin VI ready for work. PMID- 26896432 TI - Abnormality on a plain film chest radiograph. PMID- 26896433 TI - Suspected Large Vessel Occlusion: Should Emergency Medical Services Transport to the Nearest Primary Stroke Center or Bypass to a Comprehensive Stroke Center With Endovascular Capabilities? PMID- 26896434 TI - Early Versus Late Assessment of Stroke Outcome. PMID- 26896435 TI - Embolic Stroke, Atrial Fibrillation, and Microbleeds: Is There a Role for Anticoagulation? PMID- 26896436 TI - Comparative speed of kill of sarolaner (Simparica and fluralaner (Bravecto) against induced infestations of Ctenocephalides felis on dogs. AB - BACKGROUND: Fleas are the most common ectoparasite infesting dogs globally and cause direct discomfort, induce allergic reactions, and transmit pathogenic agents. Rapid speed of kill is an important characteristic for a parasiticide in order to alleviate the direct deleterious effects of fleas, reduce the impact of allergic responses, and break the flea life cycle. In this study, the speed of kill of a novel, orally administered isoxazoline parasiticide, sarolaner (Simparica), against fleas on dogs was evaluated and compared with fluralaner (Bravecto) over a 3-month period. METHODS: Based on pretreatment flea counts, 24 dogs were randomly allocated to treatment with oral sarolaner at the label rate (2 to 4 mg/kg), once a month for 3 months, or oral fluralaner (25 to 50 mg/kg), once per label directions, or placebo. Dogs were combed and live fleas counted at 8, 12, and 24 h after treatment and subsequent re-infestations on Days 14, 29, 44, 59, 74 and 90. Efficacy was determined at each time point relative to counts for placebo dogs. RESULTS: There were no adverse reactions to treatment. Three monthly doses of sarolaner provided >=97.6 % efficacy (based on arithmetic means) within 8 h of treatment or subsequent weekly re-infestations of fleas for 3 months. By 12 h, fleas were eradicated from all dogs (100 % efficacy). Significantly greater numbers of live fleas were recovered from fluralaner treated dogs at 8 h on Days 74 and 90 (P <= 0.0043) when efficacy (based on arithmetic means) was only 80.7 and 72.6 %, respectively. CONCLUSIONS: In this controlled laboratory evaluation, sarolaner had a significantly faster speed of kill against fleas than fluralaner at the end of its claimed treatment period. The rapid and consistent kill of fleas within 8 to 12 h after monthly oral doses of sarolaner indicates that this treatment will provide rapid and highly effective control of flea infestations, and suggests that it will provide relief for dogs suffering from flea allergy dermatitis, and should reduce the risk of flea-borne pathogen transmission. PMID- 26896437 TI - Circulating Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Predicts Future Risk of Cardiovascular Events Independently of Established Risk Factors. AB - BACKGROUND: The secreted protein proprotein convertase subtilisin/kexin type 9 (PCSK9) is a promising new target for lowering plasma low-density lipoprotein cholesterol and preventing cardiovascular disease (CVD). The relationship between circulating PCSK9 and incident CVD in the general population is unknown. We investigated whether serum PCSK9 concentration is associated with incident CVD in a prospective cohort study of 4232 men and women 60 years of age at the time of recruitment. METHODS AND RESULTS: Incident CVD was recorded by matching to national registries. After 15 years of follow-up, a total of 491 incident events (fatal and nonfatal myocardial infarctions, unstable angina, deaths from coronary heart disease, fatal and nonfatal ischemic strokes) were recorded. Cox proportional hazards model was used to calculate hazard ratios with 95% confidence intervals. Baseline serum PCSK9 concentration predicted incident CVD; concentration in quartile 4 compared with quartile 1 was associated with a hazard ratio of 1.69 (95% confidence interval, 1.30-2.19) after adjustment for sex. Further adjustment for low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, lipoprotein(a), triglycerides, hypertension, diabetes mellitus, smoking, overweight, obesity, physical inactivity, and statin use resulted in a decrease in the hazard ratio to 1.48 (95% confidence interval, 1.12 1.95). CONCLUSIONS: Serum PCSK9 concentration is associated with future risk of CVD even after adjustments for established CVD risk factors. Further studies are needed to confirm this observation. PMID- 26896438 TI - Tufted angioma of the maxilla: a rare case with unique clinical presentation. AB - Tufted angioma is an uncommon benign vascular tumor usually presenting in early childhood and affecting mainly the skin. It has been associated with Kasabach Merritt syndrome, a severe coagulopathy of poor prognosis. There have been very few published cases of oral tufted angiomas, and maxillary bone involvement has not been hitherto reported. We present a case of a 10-year-old Caucasian boy with an erythematous left maxillary gingival mass accompanied by subjacent hard tissue swelling. Radiologic evaluation revealed an irregular mixed radiolucent and radiopaque area in the left maxilla, accompanied by alveolar ridge erosion, cortical plate expansion, and displacement and divergence of the premolars. The histopathologic examination showed scattered irregular tufted lobules of variably sized vascular spaces inside the subepithelial connective tissue and among the underlying bone trabeculae, exhibiting a "cannonball" appearance. Immunohistochemical evaluation found positivity for CD31, CD34, and smooth muscle actin, and a final diagnosis of tufted angioma with osseous involvement was rendered. A thorough review of the pertinent literature revealed only 9 previously published intraoral tufted angioma cases, the salient demographic and clinicopathologic features of which are summarized. PMID- 26896439 TI - Embryonal Control of Yellow Seed Coat Locus ECY1 Is Related to Alanine and Phenylalanine Metabolism in the Seed Embryo of Brassica napus. AB - Seed coat color is determined by the type of pigment deposited in the seed coat cells. It is related to important agronomic traits of seeds such as seed dormancy, longevity, oil content, protein content and fiber content. In Brassica napus, inheritance of seed coat color is related to maternal effects and pollen effects (xenia effects). In this research we isolated a mutation of yellow seeded B. napus controlled by a single Mendelian locus, which is named Embryonal Control of Yellow seed coat 1 (Ecy1). Microscopy of transverse sections of the mature seed show that pigment is deposited only in the outer layer of the seed coat. Using Illumina Hisequation 2000 sequencing technology, a total of 12 GB clean data, 116* coverage of coding sequences of B. napus, was achieved from seeds 26 d after pollination (DAP). It was assembled into 172,238 independent transcripts, and 55,637 unigenes. A total of 139 orthologous genes of Arabidopsis transparent testa (TT) genes were mapped in silico to 19 chromosomes of B. napus Only 49 of the TT orthologous genes are transcribed in seeds. However transcription of all orthologs was independent of embryonal control of seed coat color. Only 55 genes were found to be differentially expressed between brown seeds and the yellow mutant. Of these 55, 50 were upregulated and five were downregulated in yellow seeds as compared to their brown counterparts. By KEGG classification, 14 metabolic pathways were significantly enriched. Of these, five pathways: phenylpropanoid biosynthesis, cyanoamino acid metabolism, plant hormone signal transduction, metabolic pathways, and biosynthesis of secondary metabolites, were related with seed coat pigmentation. Free amino acid quantification showed that Ala and Phe were present at higher levels in the embryos of yellow seeds as compared to those of brown seeds. This increase was not observed in the seed coat. Moreover, the excess amount of free Ala was exactly twice that of Phe in the embryo. The pigment substrate chalcone is synthesized from two molecules of Ala and one molecule of Phe. The correlation between accumulation of Ala and Phe, and disappearance of pigment in the yellow seeded mutant, suggests that embryonal control of seed coat color is related with Phe and Ala metabolism in the embryo of B. napus. PMID- 26896441 TI - Registry report of structural and functional cardiac abnormalities diagnosed by echocardiography in an asymptomatic population. AB - BACKGROUND: The epidemiology of heart disease is changing, with rheumatic heart disease becoming less common but degenerative valve disorders, heart failure and atrial fibrillation (AF) increasing. OBJECTIVE: We sought to determine the prevalence of structural cardiac abnormalities in the apparently symptom-free adult population within our prospective echocardiography (echo) registry. METHODS: Our echo registry comprised echo studies and associated demographic and clinical data obtained prospectively from 362 consecutive asymptomatic subjects aged 50-74 years and without known heart disease referred between 2011 and 2012 from general practices in the South East of England. RESULTS: 221 echo abnormalities were detected in 178 (49%) subjects (46% men; mean (+/-SD) age 63.9+/-9.2 years; 98% Caucasian). A major abnormality was detected in seven subjects: four had a large secundum atrial septal defect, one had critical aortic stenosis, one severe mitral regurgitation and one features of hypertrophic cardiomyopathy. Twelve subjects had left ventricular systolic dysfunction with an ejection fraction (EF) <50% (of whom 10 had EF <40%). Four subjects had AF. Minor echo abnormalities were evident in the remaining 171 (47%) subjects. Abnormalities were commoner in patients with cardiovascular risk factors or a history of cardiac disease than in those without (53% vs 38%). In multivariate analyses stratified by gender, for women, increased age (F=33.3, p<0.001) and systolic blood pressure (F=9.2, p=0.003) were associated with abnormal echo findings; for men, increased age (F=12.0, p<0.001) and lower cholesterol (F=4.2, p=0.042) predicted an increase in abnormal findings on echo. CONCLUSIONS: Unrecognised cardiac abnormalities are very common in middle-aged men and women with no overt symptoms. Echo offers the potential to identify the need for early intervention and treatment to improve cardiovascular outcomes. PMID- 26896442 TI - The dangers of widespread nitric oxide screening for primary ciliary dyskinesia. AB - Primary ciliary dyskinesia (PCD) is underdiagnosed and requires complex testing at specialist diagnostic centres. Measurement of nasal nitric oxide (nNO) has good sensitivity and specificity screening for PCD, but is currently usually measured at PCD centres rather than prior to referral. Proposals to include NO testing for asthma diagnoses could widen access to PCD screening if nasal mode analysers are available. Data from 282 consecutive referrals to our PCD diagnostic centre (31 PCD positive) were used to model predictive values for nNO testing with varying pretest probability and showed that predictive values were good in the referral population, but extending screening to more general populations would result in excessive false positives that may overwhelm diagnostic services. Although nNO remains a useful test, a 'normal' result with classical clinical history should still be considered for further testing. PMID- 26896443 TI - Starting too soon: upstream reading frames repress downstream translation. AB - Upstream open reading frames (uORFs) are known to regulate a few specific transcripts, and recent computational and experimental studies have suggested candidate uORF regulation across the genome. In this issue, Johnstone et al (2016) use ribosome profiling to identify translated uORFs and measure their effects on downstream translation. Furthermore, they show that regulatory uORFs are conserved across species and subject to selective constraint. Recognizing the potential of uORFs in regulating translation expands our understanding of the dynamic regulation of gene expression. PMID- 26896440 TI - Neurofibromin Loss of Function Drives Excessive Grooming in Drosophila. AB - Neurofibromatosis I is a common genetic disorder that results in tumor formation, and predisposes individuals to a range of cognitive/behavioral symptoms, including deficits in attention, visuospatial skills, learning, language development, and sleep, and autism spectrum disorder-like traits. The nf1-encoded neurofibromin protein (Nf1) exhibits high conservation, from the common fruit fly, Drosophila melanogaster, to humans. Drosophila provides a powerful platform to investigate the signaling cascades upstream and downstream of Nf1, and the fly model exhibits similar behavioral phenotypes to mammalian models. In order to understand how loss of Nf1 affects motor behavior in flies, we combined traditional activity monitoring with video analysis of grooming behavior. In nf1 mutants, spontaneous grooming was increased up to 7x. This increase in activity was distinct from previously described dopamine-dependent hyperactivity, as dopamine transporter mutants exhibited slightly decreased grooming. Finally, we found that relative grooming frequencies can be compared in standard activity monitors that measure infrared beam breaks, enabling the use of activity monitors as an automated method to screen for grooming phenotypes. Overall, these data suggest that loss of nf1 produces excessive activity that is manifested as increased grooming, providing a platform to dissect the molecular genetics of neurofibromin signaling across neuronal circuits. PMID- 26896446 TI - Circulating Tumor Cells: A Review of Non-EpCAM-Based Approaches for Cell Enrichment and Isolation. AB - BACKGROUND: Circulating tumor cells (CTCs) are biomarkers for noninvasively measuring the evolution of tumor genotypes during treatment and disease progression. Recent technical progress has made it possible to detect and characterize CTCs at the single-cell level in blood. CONTENT: Most current methods are based on epithelial cell adhesion molecule (EpCAM) detection, but numerous studies have demonstrated that EpCAM is not a universal marker for CTC detection because it fails to detect both carcinoma cells that undergo epithelial mesenchymal transition (EMT) and CTCs of mesenchymal origin. Moreover, EpCAM expression has been found in patients with benign diseases. A large proportion of the current studies and reviews about CTCs describe EpCAM-based methods, but there is evidence that not all tumor cells can be detected using this marker. Here we describe the most recent EpCAM-independent methods for enriching, isolating, and characterizing CTCs on the basis of physical and biological characteristics and point out the main advantages and disadvantages of these methods. SUMMARY: CTCs offer an opportunity to obtain key biological information required for the development of personalized medicine. However, there is no universal marker of these cells. To strengthen the clinical utility of CTCs, it is important to improve existing technologies and develop new, non-EpCAM-based systems to enrich and isolate CTCs. PMID- 26896447 TI - Tissue Factor: A Conventional or Alternative Target in Cancer Therapy. AB - BACKGROUND: Tissue factor (TF) is an evolutionary conserved glycoprotein that plays an important role in the pathogenesis of cancer. TF is expressed in 2 naturally occurring protein isoforms, membrane-bound full-length (fl)TF and soluble alternatively spliced (as)TF. Both isoforms have been shown to affect a variety of pathophysiologically relevant functions, such as tumor-associated angiogenesis, thrombogenicity, tumor growth, and metastasis. Therefore, targeting TF either by direct inhibition or indirectly, i.e., on a posttranscriptional level, offers a novel therapeutic option for cancer treatment. CONTENT: In this review we summarize the latest findings regarding the role of TF and its isoforms in cancer biology. Moreover, we briefly depict and discuss the therapeutic potential of direct and/or indirect inhibition of TF activity and expression for the treatment of cancer. SUMMARY: asTF and flTF play important and often distinct roles in cancer biology, i.e., in thrombogenicity and angiogenesis, which is mediated by isoform-specific signal transduction pathways. Therefore, both TF isoforms and downstream signaling are promising novel therapeutic targets in malignant diseases. PMID- 26896445 TI - Upstream ORFs are prevalent translational repressors in vertebrates. AB - Regulation of gene expression is fundamental in establishing cellular diversity and a target of natural selection. Untranslated mRNA regions (UTRs) are key mediators of post-transcriptional regulation. Previous studies have predicted thousands of ORFs in 5'UTRs, the vast majority of which have unknown function. Here, we present a systematic analysis of the translation and function of upstream open reading frames (uORFs) across vertebrates. Using high-resolution ribosome footprinting, we find that (i)uORFs are prevalent within vertebrate transcriptomes, (ii) the majority show signatures of active translation, and (iii)uORFs act as potent regulators of translation and RNA levels, with a similar magnitude to miRNAs. Reporter experiments reveal clear repression of downstream translation by uORFs/oORFs. uORF number, intercistronic distance, overlap with the CDS, and initiation context most strongly influence translation. Evolution has targeted these features to favor uORFs amenable to regulation over constitutively repressive uORFs/oORFs. Finally, we observe that the regulatory potential of uORFs on individual genes is conserved across species. These results provide insight into the regulatory code within mRNA leader sequences and their capacity to modulate translation across vertebrates. PMID- 26896444 TI - Structural mechanism of ATP-dependent DNA binding and DNA end bridging by eukaryotic Rad50. AB - The Mre11-Rad50-Nbs1 (MRN) complex is a central factor in the repair of DNA double-strand breaks (DSBs). The ATP-dependent mechanisms of how MRN detects and endonucleolytically processes DNA ends for the repair by microhomology-mediated end-joining or further resection in homologous recombination are still unclear. Here, we report the crystal structures of the ATPgammaS-bound dimer of the Rad50(NBD)(nucleotide-binding domain) from the thermophilic eukaryote Chaetomium thermophilum(Ct) in complex with either DNA or CtMre11(RBD)(Rad50-binding domain) along with small-angle X-ray scattering and cross-linking studies. The structure and DNA binding motifs were validated by DNA binding experiments in vitro and mutational analyses in Saccharomyces cerevisiae in vivo Our analyses provide a structural framework for the architecture of the eukaryotic Mre11-Rad50 complex. They show that a Rad50 dimer binds approximately 18 base pairs of DNA along the dimer interface in anATP-dependent fashion or bridges two DNA ends with a preference for 3' overhangs. Finally, our results may provide a general framework for the interaction of ABC ATPase domains of the Rad50/SMC/RecN protein family with DNA. PMID- 26896448 TI - Comparative speed of kill of sarolaner (Simparica) and spinosad plus milbemycin oxime (Trifexis) against induced infestations of Ctenocephalides felis on dogs. AB - BACKGROUND: Fleas are a ubiquitous ectoparasite infesting dogs and cause direct discomfort, allergic reactions and are responsible for the transmission of several pathogens. The rapid speed of kill of a parasiticide is important to alleviate the direct deleterious effects of fleas, reduce the impact of allergic responses, and break the flea life cycle. In this study, the speed of kill of a novel orally administered isoxazoline parasiticide, sarolaner (Simparica) against fleas on dogs was evaluated and compared with spinosad in combination with milbemycin oxime (Trifexis) for 5 weeks after a single oral dose. METHODS: Twenty four dogs were randomly allocated to treatment with a single oral dose per product label of sarolaner (2 to 4 mg/kg), spinosad/milbemycin oxime (30 to 60 mg/kg / 0.2 to 0.4 mg/kg), or placebo based on pretreatment flea counts. Dogs were combed and live fleas counted at 8, 12, and 24 h after treatment and subsequent re-infestations on Days 7, 14, 21, 28, and 35. Efficacy (reduction in live flea counts) of each treatment was determined at each time point relative to counts for placebo dogs. RESULTS: There were no adverse reactions to treatment. A single oral dose of sarolaner provided >=94.0 % efficacy (based on geometric means) within 8 h of treatment or subsequent weekly re-infestations of fleas to Day 35. By 12 h, fleas were eradicated from all dogs and they remained flea free at 24 h. Significantly greater numbers of live fleas were recovered from spinosad/milbemycin oxime-treated dogs at 8 h from Day 21 to Day 35 (P <= 0.0085), and at 12 and 24 h on Day 35 (P <= 0.0002). CONCLUSIONS: In this controlled laboratory evaluation, dogs treated with sarolaner had significantly fewer live fleas than spinosad/milbemycin oxime- treated dogs at 8 h after re infestation from Day 21 after a single oral dose. The rapid and consistent kill of fleas after a single oral dose of sarolaner over 35 days indicates that this treatment should provide highly effective control of flea infestations, relief for dogs afflicted with flea allergy dermatitis, and also reduce the risk of transmission of flea-borne pathogens. PMID- 26896450 TI - Management of fractures of the distal radius 4 years after the introduction of national guidelines. PMID- 26896452 TI - Traumatic midcarpal dislocation in an 8-year-old girl. PMID- 26896451 TI - Results of measurement of inter-crease distances in the hand. PMID- 26896449 TI - Reduction in mitochondrial iron alleviates cardiac damage during injury. AB - Excess cellular iron increases reactive oxygen species (ROS) production and causes cellular damage. Mitochondria are the major site of iron metabolism and ROS production; however, few studies have investigated the role of mitochondrial iron in the development of cardiac disorders, such as ischemic heart disease or cardiomyopathy (CM). We observe increased mitochondrial iron in mice after ischemia/reperfusion (I/R) and in human hearts with ischemic CM, and hypothesize that decreasing mitochondrial iron protects against I/R damage and the development of CM. Reducing mitochondrial iron genetically through cardiac specific overexpression of a mitochondrial iron export protein or pharmacologically using a mitochondria-permeable iron chelator protects mice against I/R injury. Furthermore, decreasing mitochondrial iron protects the murine hearts in a model of spontaneous CM with mitochondrial iron accumulation. Reduced mitochondrial ROS that is independent of alterations in the electron transport chain's ROS producing capacity contributes to the protective effects. Overall, our findings suggest that mitochondrial iron contributes to cardiac ischemic damage, and may be a novel therapeutic target against ischemic heart disease. PMID- 26896453 TI - Trapezium anatomy as a radiographic reference for optimal cup orientation in total trapeziometacarpal joint arthroplasty. AB - In trapeziometacarpal arthroplasty, correct implant position may be necessary to prevent complications such as dislocation, component loosening and premature wear. The metacarpal stem more easily fits anatomically. However, the cup in the trapezium is not anatomical and guidelines for its orientation are not uniformly defined. We determined the centre of the range of motion of the trapeziometacarpal joint in 30 healthy patients on postero-anterior and lateral radiographs and its relationship to the proximal articular surface of the trapezium. Our study suggests that in thumb carpo-metacarpal total joint arthroplasty, the prosthetic cup in the trapezium should be placed parallel to the proximal articular surface of the trapezium and combined with a metacarpal neck with 7 degrees palmar offset. This should optimize arthroplasty ranges of motion and may minimize the risk of postoperative complications. Our study provides a reference for the surgeon to check correct cup alignment intra operatively with fluoroscopy. PMID- 26896454 TI - Asymmetric six-strand core sutures enhance tendon fatigue strength and the optimal asymmetry. AB - Under cyclic loading, we recorded the fatigue strength of a six-strand tendon repair with different symmetry in the lengths of suture purchase in two stumps of 120 dental rolls and in 30 porcine tendons. First, the strengths of the repairs with 1, 2, 3, 4 and 5 mm asymmetry were screened using the dental rolls. The asymmetric core suture repairs were then made with a Kessler repair of equal suture purchase (10 mm) in two tendon stumps, and shifting two other Kessler repairs by 1, 3 or 5 mm, respectively, along the longitudinal axis of the tendon in relation to the first (symmetric) Kessler repair. The core repairs with 3 mm or more asymmetry in suture purchases in two tendon ends showed significantly greater fatigue strength and significantly smaller gaps compared with 1 mm asymmetry in core suture repair. Our results support that asymmetric placement of core sutures in two tendon ends favour resisting gapping at the repair site and 3 mm or more asymmetry is needed to produce such beneficial effects. PMID- 26896455 TI - Natural history and factors associated with ulnar-sided wrist pain in distal radial fractures treated by plate fixation. AB - We documented longitudinal changes in the incidence of ulnar-sided wrist pain after distal radial fractures treated by plate fixation and identified factors associated with ulnar-sided wrist pain. A total of 140 patients were enrolled in this study. Radiographs were taken 3 months after operation, and were used to measure radial inclination, anterior angulation and ulnar variance, and to identify the presence of an ulnar styloid fracture. Clinical assessments at the same time included grip strengths, ranges of wrist motion and the patient-rated wrist evaluation questionnaire. The presence of ulnar-sided wrist pain was noted at each follow-up visit. The incidence of ulnar-sided wrist pain decreased significantly with time after surgery (22 patients at 3 months, 11 patients at 6 months and three patients at 12 months). The mean age, sex, the presence of an ulnar styloid fracture and the classification of the distal radial fracture were not factors that were associated with a higher incidence of ulnar-sided wrist pain, but there was an association between higher patient-rated wrist evaluation scores and the presence of ulnar-sided wrist pain. LEVEL OF EVIDENCE: Prognosis, Level IV. PMID- 26896456 TI - Comparative speed of kill of sarolaner (Simparica) and afoxolaner (NexGard) against induced infestations of Rhipicephalus sanguineus s.l. on dogs. AB - BACKGROUND: The brown dog tick, Rhipicephalus sanguineus sensu lato, commonly infests dogs globally, is the major vector of the pathogen that causes canine monocytic ehrlichiosis and also transmits Babesia vogeli. A rapid speed of kill of a parasiticide is essential to reduce the direct deleterious effects of tick infestation and the risk of tick-borne pathogen transmission. The speed of kill of a novel orally administered isoxazoline parasiticide, sarolaner (Simparica), against R. sanguineus sensu lato on dogs was evaluated and compared with afoxolaner (NexGard) for 5 weeks after a single oral dose. METHODS: Based on pretreatment tick counts, 24 dogs were randomly allocated to oral treatment with either placebo, or label doses of sarolaner (2-4 mg/kg) or afoxolaner (2.5-6.8 mg/kg). Dogs were examined and live ticks counted at 8, 12, and 24 h after treatment and subsequent re-infestations on Days 7, 14, 21, 28, and 35. Efficacy was determined at each time point relative to counts for placebo dogs. RESULTS: There were no adverse reactions to treatment. Based on geometric means, sarolaner provided >94 % efficacy within 8 h of treatment, and >99 % after 12 and 24 h. Against subsequent weekly re-infestations of ticks, sarolaner achieved >=91.7 % efficacy (based on geometric means) to Day 35 at 24 h. Sarolaner significantly reduced tick counts versus placebo on Days 0 and 28 at 8 h (P <= 0.0390), on Days 0 to 14 and 28 at 12 h (P <= 0.0142), and on all days at 24 h (P < 0.0001). By comparison, tick counts for afoxolaner were significantly lower than placebo at 8 h on Days 0 and 28 (P <= 0.0117), at 12 h on Day 0 only (P < 0.0001), and on all days at 24 h (P <= 0.0078). Significantly more live ticks were recovered from afoxolaner-treated dogs than from sarolaner-treated dogs at 8 and 12 h after treatment (P <= 0.0286), at 12 h after re-infestation on Days 7 and 28 (P <= 0.04630), and at 24 h after re-infestations from Day 7 to Day 35 (P <= 0.0119). At 24 h, efficacy (based on geometric mean counts) of afoxolaner was less than 90 % from Day 7 onwards, and declined to less than 45 % by Day 35, while efficacy for sarolaner was >90 % for 35 days. CONCLUSIONS: In this controlled laboratory evaluation, sarolaner had a faster speed of kill against R. sanguineus sensu lato than afoxolaner. The rapid and consistent kill of ticks within 24 h after a single oral dose of sarolaner over 35 days indicates that this treatment will provide highly effective and reliable control of ticks over the entire treatment interval and should reduce the risk of tick-borne pathogen transmission. PMID- 26896457 TI - Increasing detection rates for diminutive adenomas: are we on the right track? PMID- 26896458 TI - Algorithm to rule out clinically significant portal hypertension combining Shear wave elastography of liver and spleen: a prospective multicentre study. PMID- 26896460 TI - The impact of three-dimensional imaging on polyp detection during colonoscopy: a proof of concept study. PMID- 26896459 TI - Detection rate and predictive factors of sessile serrated polyps in an organised colorectal cancer screening programme with immunochemical faecal occult blood test: the EQuIPE study (Evaluating Quality Indicators of the Performance of Endoscopy). AB - OBJECTIVES: To assess detection rate and predictive factors of sessile serrated polyps (SSPs) in organised colorectal cancer (CRC) screening programmes based on the faecal immunochemical test (FIT). DESIGN: Data from a case series of colonoscopies of FIT-positive subjects were provided by 44 Italian CRC screening programmes. Data on screening history, endoscopic procedure and histology results, and additional information on the endoscopy centre and the endoscopists were collected, including the age-standardised and sex-standardised adenoma detection rate (ADR) of the individual endoscopists. The SSP detection rate (SSP DR) was assessed for the study population. To identify SSP-predictive factors, multilevel analyses were performed according to patient/centre/endoscopist characteristics. RESULTS: We analysed 72 021 colonoscopies, of which 1295 presented with at least one SSP (SSP-DR 1.8%; 95% CI 1.7% to 1.9%). At the per patient level, SSP-DR was associated with males (OR 1.35; 95% CI 1.17 to 1.54) and caecal intubation (OR 3.75; 95% CI 2.22 to 6.34), but not with the FIT round. The presence of at least one advanced adenoma was more frequent among subjects with SSPs than those without (OR 2.08; 95% CI 1.86 to 2.33). At the per endoscopist level, SSP-DR was associated with ADR (third vs first ADR quartile: OR 1.55; 95% CI 1.03 to 2.35; fourth vs first quartile: OR 1.89; 95% CI 1.24 to 2.90). CONCLUSION: The low prevalence of SSPs and the lack of association with the FIT round argue against SSP as a suitable target for FIT-based organised programmes. Strict association of SSP-DR with the key colonoscopy quality indicators, namely caecal intubation rate and high ADR further marginalises the need for SSP-specific quality indicators in FIT-based programmes. PMID- 26896464 TI - "Walking Between the Raindrops": Intimate Partner Violence in the Ultra-Orthodox Society in Israel From Social Workers' Perspective. AB - Intimate partner violence (IPV) in faith-based communities has unique characteristics that social workers should consider. This qualitative study examines how social workers describe their encounter with abused Jewish ultra Orthodox women. In-depth interviews were conducted among 24 social workers (one man, 23 women: four were ultra-Orthodox, 19 were modern Orthodox, and one was secular); all respondents worked in the public sector, welfare offices, and non profit organizations in ultra-Orthodox communities. Three major themes emerged: (a) "There is no guardian against unchastity": Is there no safe haven when it comes to domestic violence?; (b) "I'm not religious enough, not disciplined enough": describing the experience of violence in the therapeutic encounter; and (c) "walking between the raindrops": culturally sensitive social work in the context of IPV. Findings and implications are discussed in the context of cultural sensitivity. PMID- 26896463 TI - Knockdown of TMEM14A expression by RNAi inhibits the proliferation and invasion of human ovarian cancer cells. AB - Transmembrane protein 14A (TMEM14A) is a member of TMEMs. Alterations in TMEMs expression have been identified in several types of cancer, but the expression and function of TMEM14A in ovarian cancer is still unclear. Here, analysis on the expression data of the Cancer Genome Atlas (TCGA) ovarian serous cystadenocarcinoma (OV) dataset demonstrated the overexpression of TMEM14A in ovarian cancer tissues compared with normal tissues, which was consistent with our real-time PCR analysis on ovarian cancer and normal tissues collected from 30 patients. In addition, TMEM14A knockdown in two ovarian cancer cell lines, A2780 and HO-8910, reduced cell proliferation, causes cell cycle arrest and suppressed cell invasion. Moreover, silencing of TMEM14A notably repressed G1/S cell cycle transition and cell invasion via down-regulating the expression of cell cycle related proteins (Cyclin D1, Cyclin E and PCNA) and metastasis-related proteins (MMP-2 and MMP-9), respectively. TMEM14A knockdown significantly reduced the phosphorylation status of Smad2 and Smad3, downstream effectors of TGF-beta signalling. In summary, these results indicate that TMEM14A has a pro-tumorigenic effect in ovarian cancer cells, suggesting an important role of this protein in ovarian cancer oncogenesis and metastasis. PMID- 26896465 TI - Comparison of intra-individual coefficients of variation on the paired sampling data when inter-individual variations are different between measures. AB - BACKGROUND: Pain intensities of patients are repeatedly measured by Visual Analog Scale (VAS) and Pain Vision (PV) in a clinical research. Two measurements by VAS and PV are performed at the same time. In order to evaluate within patient consistency, intra-individual coefficient of variations (CVs) are compared between measures assuming that the pain status of each patient is stable during the research period. The correlated samples and different inter-individual variation due to different scales of the measures should be taken into account in statistical analysis. The adjustment of covariates will improve the estimation of population mean values of the measures. METHODS: In this paper, statistical approach to compare the intra-individual CVs is proposed. The approach consists of two steps: (1) estimating population mean values and intra-individual variances of the pain intensities by measure in a mixed effect model framework, (2) computing intra-individual CVs and comparing them between measures. The mixed effect model includes measure and some variables as fixed effects and subject by measure as a random effect. The different inter-individual variations between measures and their covariance reflect the paired sampling in the variance component. The confidence interval of the difference of intra-individual CVs is constructed using the asymptotic normality and the delta method. Bootstrap method is available if sample size is small. RESULTS: The proposed approach is illustrated using pain research data. Measure (VAS and PV), age and sex are included in the model as fixed effects. The confidence intervals of the difference of intra-individual CVs between measures are estimated by the asymptotic theory and by bootstrap using a subgroup resampling, respectively. Both confidence intervals are similar. CONCLUSION: The proposed approach is useful to compare two intra-individual CVs taking it into account to reflect the paired sampling, different inter-individual variations between measures and some covariates. Although the inclusion of covariates did not improve the goodness-of fit in the illustration, the proposed model with covariates will improve the accuracy and/or precision if covariates truly influence response variable. This approach can be applicable with small modification to various situations. PMID- 26896468 TI - Leadless cardiac pacemaker as alternative in case of congenital vascular abnormality and pocket infection. PMID- 26896466 TI - Determinants and prognostic value of Galectin-3 in patients with aortic valve stenosis. AB - OBJECTIVE: Myocardial fibrosis has been proposed as an outcome predictor in asymptomatic patients with severe aortic stenosis (AS) that may lead to consider prophylactic surgery. It can be detected using MRI but its widespread use is limited and development of substitute biomarkers is highly desirable. We analysed the determinants and prognostic value of galectin-3, one promising biomarker linked to myocardial fibrosis. METHODS: Patients with at least mild degenerative AS enrolled between 2006 and 2013 in two ongoing studies, COFRASA/GENERAC (COhorte Francaise de Retrecissement Aortique du Sujet Age/GENEtique du Retrecissement Aortique), aiming at assessing the determinants of AS occurrence and progression, constituted our population. RESULTS: We prospectively enrolled 583 patients. The mean galectin-3 value was 14.3+/-5.6 ng/mL. There was no association between galectin-3 and functional status (p=0.55) or AS severity (p=0.58). Independent determinants of galectin-3 were age (p=0.0008), female gender (p=0.04), hypertension (p=0.002), diabetes (p=0.02), reduced left ventricular ejection fraction (p=0.01), diastolic dysfunction (E/e', p=0.02) and creatinine clearance (p<0.0001). Among 330 asymptomatic patients at baseline, galectin-3 was neither predictive of outcome in univariate analysis (p=0.73), nor after adjustment for age, gender, rhythm, creatinine clearance and AS severity (p=0.66). CONCLUSIONS: In a prospective cohort of patients with a wide range of AS severity, galectin-3 was not associated with AS severity or functional status. Main determinants of galectin-3 were age, hypertension and renal function. Galectin-3 did not provide prognostic information on the occurrence of AS-related events. Our results do not support the use of galectin-3 in the decision-making process of asymptomatic patients with AS. TRIAL REGISTRATION NUMBER: COFRASA NCT00338676 and GENERAC CT00647088. PMID- 26896467 TI - Magnetic resonance imaging-compatible circular mapping catheter: an in vivo feasibility and safety study. AB - Aims: Interventional cardiac catheter mapping is routinely guided by X-ray fluoroscopy, although radiation exposure remains a significant concern. Feasibility of catheter ablation for common flutter has recently been demonstrated under magnetic resonance imaging (MRI) guidance. The benefit of catheter ablation under MRI could be significant for complex arrhythmias such as atrial fibrillation (AF), but MRI-compatible multi-electrode catheters such as Lasso have not yet been developed. This study aimed at demonstrating the feasibility and safety of using a multi-electrode catheter [magnetic resonance (MR)-compatible Lasso] during MRI for cardiac mapping. We also aimed at measuring the level of interference between MR and electrophysiological (EP) systems. Methods and results: Experiments were performed in vivo in sheep (N = 5) using a multi-electrode, circular, steerable, MR-compatible diagnostic catheter. The most common MRI sequences (1.5T) relevant for cardiac examination were run with the catheter positioned in the right atrium. High-quality electrograms were recorded while imaging with a maximal signal-to-noise ratio (peak-to-peak signal amplitude/peak-to-peak noise amplitude) ranging from 5.8 to 165. Importantly, MRI image quality was unchanged. Artefacts induced by MRI sequences during mapping were demonstrated to be compatible with clinical use. Phantom data demonstrated that this 10-pole circular catheter can be used safely with a maximum of 4 degrees C increase in temperature. Conclusions: This new MR-compatible 10-pole catheter appears to be safe and effective. Combining MR and multipolar EP in a single session offers the possibility to correlate substrate information (scar, fibrosis) and EP mapping as well as online monitoring of lesion formation and electrical endpoint. PMID- 26896470 TI - Episode-Based Approaches to Measuring Health Care Quality. AB - Most currently available quality measures reflect point-in-time provider tasks, providing a limited and fragmented assessment of care. The concept of episodes of care could be used to develop quality measurement approaches that reflect longer periods of care. With input from clinical experts, we constructed episode-of-care frameworks for six illustrative conditions and identified potential gaps and measure development priority areas. Episode-based measures could assess changes in health outcomes ("delta measures"), the amount of time during an episode in which a patient has suboptimal health status ("integral measures"), quality contingent upon events occurring previously ("contingent measures"), and composites of measures throughout the episode. This article identifies a number of challenges that will need to be addressed to advance operationalization of episode-based quality measurement. PMID- 26896471 TI - Media researchers must understand the audience too. PMID- 26896472 TI - Barriers and opportunities for hepatitis B testing and contact tracing in a UK Somali population: a qualitative study. AB - BACKGROUND: Chronic hepatitis B virus (HBV) infection frequently causes liver disease, and early identification can improve outcome. The burden of chronic HBV infection in many economically developed nations lies in migrant populations. Targeted HBV testing of migrants, and contact tracing for those diagnosed, are public health objectives but uptake has been fragmentary. This qualitative study aimed to investigate understanding of hepatitis B and response to testing and contact tracing amongst people of Somali ethnicity living in Bristol, UK. METHODS: The views of 30 people of Somali ethnicity living in Bristol were explored through focus groups and semi-structured interviews. Transcripts of audio-recorded interviews and focus groups were imported into NVivo10 and inductive thematic analysis undertaken. RESULTS: Most participants lacked awareness of hepatitis B, and often co-identified hepatitis B with 'jaundice'. There were frequent misconceptions regarding transmission, natural history and diagnosis, with hepatitis B commonly viewed as a relatively trivial, short lived, symptomatic disease. Hepatitis B was generally not stigmatised. Lack of understanding of the disease was cited as the major barrier to targeted testing and contact tracing. CONCLUSION: These findings suggest public health initiatives to promote hepatitis B testing and contact tracing within migrant Somali populations should focus on improving hepatitis B understanding, particularly its natural history and diagnosis, and avoid translation of 'hepatitis B' into terms meaning 'jaundice' to address misperception of low susceptibility and low severity. PMID- 26896473 TI - Tetrahydrobiopterin Supplementation Improves Endothelial Function But Does Not Alter Aortic Stiffness in Patients With Rheumatoid Arthritis. AB - BACKGROUND: Rheumatoid arthritis is a systemic inflammatory condition associated with increased cardiovascular risk that may be due to underlying endothelial dysfunction and subsequent aortic stiffening. We hypothesized that supplementation with tetrahydrobiopterin (BH4) would recouple endothelial nitric oxide synthase and thus improve endothelial function and consequently reduce aortic stiffness. METHODS AND RESULTS: We conducted 2 randomized, double-blinded, placebo-controlled crossover studies examining 2 separate regimens: an acute regimen, with a single dose of BH4 400 mg versus placebo (n=18), and a short-term regimen, composed of a 1-week treatment with BH4 400 mg once daily versus placebo (n=15). Flow-mediated dilatation and aortic pulse wave velocity were studied 4 times, before and after each treatment phase. Acute BH4 supplementation led to an improvement of flow-mediated dilatation, whereas placebo had no effect (mean+/-SD of effect difference 2.56+/-4.79%; P=0.03). Similarly, 1-week treatment with BH4 improved endothelial function, but there was no change with placebo (mean+/-SD of effect difference 3.50+/-5.05%; P=0.02). There was no change in aortic pulse wave velocity following acute or short-term BH4 supplementation or placebo (mean+/-SD of effect difference: acute 0.09+/-0.67 m/s, P=0.6; short-term 0.03+/-1.46 m/s, P=0.9). CONCLUSION: Both acute and short-term supplementation with oral BH4 improved endothelial function but not aortic stiffness. This result suggests that BH4 supplementation may be beneficial for patients with rheumatoid arthritis by improving endothelial dysfunction and potentially reducing risk of cardiovascular disease. There appears to be no causal relationship between endothelial function and aortic stiffness, suggesting that they occur in parallel, although they may share common risk factors such as inflammation. PMID- 26896474 TI - Post-Procedural Troponin Elevation and Clinical Outcomes Following Transcatheter Aortic Valve Implantation. AB - BACKGROUND: Biomarkers of myocardial injury increase frequently during transcatheter aortic valve implantation (TAVI). The impact of postprocedural cardiac troponin (cTn) elevation on short-term outcomes remains controversial, and the association with long-term prognosis is unknown. METHODS AND RESULTS: We evaluated 577 consecutive patients with severe aortic stenosis treated with TAVI between 2007 and 2012. Myocardial injury, defined according to the Valve Academic Research Consortium (VARC)-2 as post-TAVI cardiac troponin T (cTnT) >15* the upper limit of normal, occurred in 338 patients (58.1%). In multivariate analyses, myocardial injury was associated with higher risk of all-cause mortality at 30 days (adjusted hazard ratio [HR], 8.77; 95% CI, 2.07-37.12; P=0.003) and remained a significant predictor at 2 years (adjusted HR, 1.98; 95% CI, 1.36-2.88; P<0.001). Higher cTnT cutoffs did not add incremental predictive value compared with the VARC-2-defined cutoff. Whereas myocardial injury occurred more frequently in patients with versus without coronary artery disease (CAD), the relative impact of cTnT elevation on 2-year mortality did not differ between patients without CAD (adjusted HR, 2.59; 95% CI, 1.27-5.26; P=0.009) and those with CAD (adjusted HR, 1.71; 95% CI, 1.10-2.65; P=0.018; P for interaction=0.24). Mortality rates at 2 years were lowest in patients without CAD and no myocardial injury (11.6%) and highest in patients with complex CAD (SYNTAX score >22) and myocardial injury (41.1%). CONCLUSIONS: VARC-2-defined cTnT elevation emerged as a strong, independent predictor of 30-day mortality and remained a modest, but significant, predictor throughout 2 years post-TAVI. The prognostic value of cTnT elevation was modified by the presence and complexity of underlying CAD with highest mortality risk observed in patients combining SYNTAX score >22 and evidence of myocardial injury. PMID- 26896475 TI - Misinterpretation of the Determinants of Elevated Forward Wave Amplitude Inflates the Role of the Proximal Aorta. AB - BACKGROUND: The hemodynamic basis for increased pulse pressure (PP) with aging remains controversial. The classic paradigm attributes a predominant role to increased pulse wave velocity (PWV) and premature wave reflections (WRs). A controversial new paradigm proposes increased forward pressure wave amplitude (FWA), attributed to proximal aortic characteristic impedance (Zc), as the predominant factor, with minor contributions from WRs. Based on theoretical considerations, we hypothesized that (rectified) WRs drive the increase in FWA, and that the forward pressure wave does not depend solely on the interaction between flow and Zc (QZc product). METHODS AND RESULTS: We performed 3 substudies: (1) open-chest anesthetized dog experiments (n=5); (2) asymmetric T tube model-based study; and (3) human study in a diverse clinical population (n=193). Animal experiments demonstrated that FWA corresponds to peak QZc only when WRs are minimal. As WRs increased, FWA was systematically greater than QZc and peaked well after peak flow, analogous to late-systolic peaking of pressure attributable to WRs. T-tube modeling confirmed that increased/premature WRs resulted in increased FWA. Magnitude and timing of WRs explained 80.8% and 74.3% of the variability in the difference between FWA and peak QZc in dog and human substudies, respectively. CONCLUSIONS: Only in cases of minimal reflections does FWA primarily reveal the interaction between peak aortic flow and proximal aortic diameter/stiffness. FWA is strongly dependent on rectified reflections. If interpreted out of context with the hemodynamic principles of its derivation, the FWA paradigm inappropriately amplifies the role of the proximal aorta in elevation of FWA and PP. PMID- 26896476 TI - Reduction in Kv Current Enhances the Temporal Dispersion of the Action Potential in Diabetic Myocytes: Insights From a Novel Repolarization Algorithm. AB - BACKGROUND: Diabetes is associated with prolongation of the QT interval of the electrocardiogram and enhanced dispersion of ventricular repolarization, factors that, together with atherosclerosis and myocardial ischemia, may promote the occurrence of electrical disorders. Thus, we tested the possibility that alterations in transmembrane ionic currents reduce the repolarization reserve of myocytes, leading to action potential (AP) prolongation and enhanced beat-to-beat variability of repolarization. METHODS AND RESULTS: Diabetes was induced in mice with streptozotocin (STZ), and effects of hyperglycemia on electrical properties of whole heart and myocytes were studied with respect to an untreated control group (Ctrl) using electrocardiographic recordings in vivo, ex vivo perfused hearts, and single-cell patch-clamp analysis. Additionally, a newly developed algorithm was introduced to obtain detailed information of the impact of high glucose on AP profile. Compared to Ctrl, hyperglycemia in STZ-treated animals was coupled with prolongation of the QT interval, enhanced temporal dispersion of electrical recovery, and susceptibility to ventricular arrhythmias, defects observed, in part, in the Akita mutant mouse model of type I diabetes. AP was prolonged and beat-to-beat variability of repolarization was enhanced in diabetic myocytes, with respect to Ctrl cells. Density of Kv K(+) and L-type Ca(2+) currents were decreased in STZ myocytes, in comparison to cells from normoglycemic mice. Pharmacological reduction of Kv currents in Ctrl cells lengthened AP duration and increased temporal dispersion of repolarization, reiterating features identified in diabetic myocytes. CONCLUSIONS: Reductions in the repolarizing K(+) currents may contribute to electrical disturbances of the diabetic heart. PMID- 26896477 TI - Sex Differences in Cardiovascular Disease Risk of Ghanaian- and Nigerian-Born West African Immigrants in the United States: The Afro-Cardiac Study. AB - BACKGROUND: The number of African immigrants in the United States grew 40-fold between 1960 and 2007, from 35 355 to 1.4 million, with a large majority from West Africa. This study sought to examine the prevalence of cardiovascular disease (CVD) risk factors and global CVD risk and to identify independent predictors of increased CVD risk among West African immigrants in the United States. METHODS AND RESULTS: This cross-sectional study assessed West African (Ghanaian and Nigerian) immigrants aged 35-74 years in the Baltimore-Washington metropolitan area. The mean age of participants was 49.5+/-9.2 years, and 58% were female. The majority (95%) had >=1 of the 6 CVD risk factors. Smoking was least prevalent, and overweight or obesity was most prevalent, with 88% having a body mass index (in kg/m(2)) >=25; 16% had a prior diagnosis of diabetes or had fasting blood glucose levels >=126 mg/dL. In addition, 44% were physically inactive. Among women, employment and health insurance were associated with odds of 0.09 (95% CI 0.033-0.29) and 0.25 (95% CI 0.09-0.67), respectively, of having a Pooled Cohort Equations estimate >=7.5% in the multivariable logistic regression analysis. Among men, higher social support was associated with 0.90 (95% CI 0.83-0.98) lower odds of having >=3 CVD risk factors but not with having a Pooled Cohort Equations estimate >=7.5%. CONCLUSIONS: The prevalence of CVD risk factors among West African immigrants was particularly high. Being employed and having health insurance were associated with lower CVD risk in women, but only higher social support was associated with lower CVD risk in men. PMID- 26896481 TI - How Thymocytes Achieve Their Fate. PMID- 26896478 TI - Allogeneic Mesenchymal Stromal Cells Transplanted Onto the Heart Surface Achieve Therapeutic Myocardial Repair Despite Immunologic Responses in Rats. AB - BACKGROUND: Transplantation of allogeneic mesenchymal stromal cells (MSCs) is a promising treatment for heart failure. We have shown that epicardial placement of cell sheets markedly increases donor cell survival and augments therapeutic effects compared with the current methods. Although immune rejection of intramyocardially injected allogeneic MSCs have been suggested, allogeneic MSCs transplanted on the heart surface (virtual space) may undergo different courses. This study aimed to elucidate immunologic response against epicardially placed allogeneic MSCs, rejection or acceptance of these cells, and their therapeutic effects for heart failure. METHODS AND RESULTS: At 4 weeks after coronary artery ligation, Lewis rats underwent epicardial placement of MSC sheets from syngeneic Lewis or allogeneic Fischer 344 rats or sham treatment. At days 3 and 10 after treatment, similar ratios (~50% and 30%, respectively) of grafted MSCs survived on the heart surface in both MSC sheet groups. By day 28, survival of syngeneic MSCs was substantially reduced (8.9%); survival of allogeneic MSCs was more extensively reduced (0.2%), suggesting allorejection. Correspondingly, allogeneic MSCs were found to have evoked an immunologic response, albeit low level, as characterized by accumulation of CD4(+) T cells and upregulation of interleukin 6. Despite this alloimmune response, the allogeneic MSC sheet achieved myocardial upregulation of reparative factors, enhanced repair of the failing myocardium, and improved cardiac function to the equivalent degree observed for the syngeneic MSC sheet. CONCLUSIONS: Allogeneic MSCs placed on the heart surface evoked an immunologic response; however, this allowed sufficient early phase donor cell survival to induce equivalent therapeutic benefits to syngeneic MSCs. Further development of this approach toward clinical application is warranted. PMID- 26896479 TI - beta3 Adrenergic Stimulation Restores Nitric Oxide/Redox Balance and Enhances Endothelial Function in Hyperglycemia. AB - BACKGROUND: Perturbed balance between NO and O2 (*-). (ie, NO/redox imbalance) is central in the pathobiology of diabetes-induced vascular dysfunction. We examined whether stimulation of beta3 adrenergic receptors (beta3 ARs), coupled to endothelial nitric oxide synthase (eNOS) activation, would re-establish NO/redox balance, relieve oxidative inhibition of the membrane proteins eNOS and Na(+) K(+) (NK) pump, and improve vascular function in a new animal model of hyperglycemia. METHODS AND RESULTS: We established hyperglycemia in male White New Zealand rabbits by infusion of S961, a competitive high-affinity peptide inhibitor of the insulin receptor. Hyperglycemia impaired endothelium-dependent vasorelaxation by "uncoupling" of eNOS via glutathionylation (eNOS-GSS) that was dependent on NADPH oxidase activity. Accordingly, NO levels were lower while O2 (*-) levels were higher in hyperglycemic rabbits. Infusion of the beta3 AR agonist CL316243 (CL) decreased eNOS-GSS, reduced O2 (*-), restored NO levels, and improved endothelium-dependent relaxation. CL decreased hyperglycemia-induced NADPH oxidase activation as suggested by co-immunoprecipitation experiments, and it increased eNOS co-immunoprecipitation with glutaredoxin-1, which may reflect promotion of eNOS de-glutathionylation by CL. Moreover, CL reversed hyperglycemia induced glutathionylation of the beta1 NK pump subunit that causes NK pump inhibition, and improved K(+)-induced vasorelaxation that reflects enhancement in NK pump activity. Lastly, eNOS-GSS was higher in vessels of diabetic patients and was reduced by CL, suggesting potential significance of the experimental findings in human diabetes. CONCLUSIONS: beta3 AR activation restored NO/redox balance and improved endothelial function in hyperglycemia. beta3 AR agonists may confer protection against diabetes-induced vascular dysfunction. PMID- 26896482 TI - Pillars Article: Coreceptor Reversal in the Thymus: Signaled CD4+8+ Thymocytes Initially Terminate CD8 Transcription Even When Differentiating into CD8+ T Cells. Immunity. 2000. 13: 59-71. PMID- 26896480 TI - Regional Implementation of a Pediatric Cardiology Syncope Algorithm Using Standardized Clinical Assessment and Management Plans (SCAMPS) Methodology. AB - BACKGROUND: Pediatric syncope is common. Cardiac causes are rarely found. We describe and assess a pragmatic approach to these patients first seen by a pediatric cardiologist in the New England region, using Standardized Clinical Assessment and Management Plans (SCAMPs). METHODS AND RESULTS: Ambulatory patients aged 7 to 21 years initially seen for syncope at participating New England Congenital Cardiology Association practices over a 2.5-year period were evaluated using a SCAMP. Findings were iteratively analyzed and the care pathway was revised. The vast majority (85%) of the 1254 patients had typical syncope. A minority had exercise-related or more problematic symptoms. Guideline-defined testing identified one patient with cardiac syncope. Syncope Severity Scores correlated well between physician and patient perceived symptoms. Orthostatic vital signs were of limited use. Largely incidental findings were seen in 10% of ECGs and 11% of echocardiograms. The 10% returning for follow-up, by design, reported more significant symptoms, but did not have newly recognized cardiac disease. Iterative analysis helped refine the approach. CONCLUSIONS: SCAMP methodology confirmed that the vast majority of children referred to the outpatient pediatric cardiology setting had typical low-severity neurally mediated syncope that could be effectively evaluated in a single visit using minimal resources. A simple scoring system can help triage patients into treatment categories. Prespecified criteria permitted the effective diagnosis of the single patient with a clear cardiac etiology. Patients with higher syncope scores still have a very low risk of cardiac disease, but may warrant attention. PMID- 26896483 TI - Correction: Ozone Inhalation Promotes CX3CR1-Dependent Maturation of Resident Lung Macrophages That Limit Oxidative Stress and Inflammation. PMID- 26896484 TI - Correction: Hyaluronan Fragments Contribute to the Ozone-Primed Immune Response to Lipopolysaccharide. PMID- 26896485 TI - Zinc Modulation of Cardiac Ryanodine Receptor Gating: Alternate Interpretation of the Interplay between Zinc and Calcium. PMID- 26896486 TI - Response to Qian and Colvin: Zinc-mediated Regulation of the Cardiac Ryanodine Receptor Occurs via Multiple Binding Sites. PMID- 26896487 TI - ThPOK represses CXXC5, which induces methylation of histone H3 lysine 9 in Cd40lg promoter by association with SUV39H1: implications in repression of CD40L expression in CD8+ cytotoxic T cells. AB - CD40 ligand is induced in CD4(+) Th cells upon TCR stimulation and provides an activating signal to B cells, making CD40 ligand an important molecule for Th cell function. However, the detailed molecular mechanisms, whereby CD40 ligand becomes expressed on the cell surface in T cells remain unclear. Here, we showed that CD40 ligand expression in CD8(+) cytotoxic T cells was suppressed by combined epigenetic regulations in the promoter region of the Cd40lg gene, such as the methylation of CpG dinucleotides, histone H3 lysine 9, histone H3 lysine 27, and histone H4 lysine 20. As the transcription factor Th-inducing pox virus and zinc finger/Kruppel-like factor (encoded by the Zbtb7b gene) is critical in Th cell development, we focused on the role of Th-inducing pox virus and zinc finger/Kruppel-like factor in CD40 ligand expression. We found that CD40 ligand expression is moderately induced by retroviral Thpok transduction into CD8(+) cytotoxic T cells, which was accompanied by a reduction of histone H3 lysine 9 methylation and histone H3 lysine 27 methylation in the promoter region of the Cd40lg gene. Th-inducing pox virus and zinc finger/Kruppel-like factor directly inhibited the expression of murine CXXC5, a CXXC-type zinc finger protein that induced histone H3 lysine 9 methylation, in part, through an interaction with the histone-lysine N-methyltransferase SUV39H1. In addition, to inhibit CD40 ligand induction in activated CD4(+) T cells by the CXXC5 transgene, our findings indicate that CXXC5 was one of the key molecules contributing to repressing CD40 ligand expression in CD8(+) cytotoxic T cells. PMID- 26896488 TI - Expression and characterization of EF-hand I loop mutants of aequorin replaced with other loop sequences of Ca2+-binding proteins: an approach to studying the EF-hand motif of proteins. AB - The binding properties of Ca(2+) to EF-hand I of aequorin (AQ) were characterized by replacing the loop sequence of EF-hand I (AQ[I]) with other known loop sequences of Ca(2+)-binding proteins, including photoproteins (aequorin, clytin I, clytin-II and mitrocomin), Renilla luciferin-binding protein (RLBP) and calmodulin (CaM). For evaluation of the binding affinity of Ca(2+) to AQ[I] mutants, the half-decay time of the maximum intensity in the luminescence reaction triggered by Ca(2+) was used as an indicator and 22 kinds of AQ[I] mutants were expressed in Escherichia coli cells. AQ[I] mutants replaced with the EF-hand I and EF-hand III from photoproteins showed sufficient luminescence activity, but it was not shown by other EF-hands from RLBP and CaM. An AQ[I] mutant with a lysine or arginine residue at the second position of the non conserved amino acid residue showed a slow-decay pattern of luminescence, indicating that the Ca(2+)-binding affinity to aequorin was reduced by a positive charge at the second position of the loop sequence. The specific loop sequence of the EF-hand I motif in aequorin caused the specific Ca(2+)-triggered luminescence pattern. PMID- 26896489 TI - The repair capacity of lung cancer cell lines A549 and H1299 depends on HMGB1 expression level and the p53 status. AB - Elucidation of the cellular components responsive to chemotherapeutic agents as cisplatin rationalizes the strategy for anticancer chemotherapy. The removal of the cisplatin/DNA lesions gives the chance to the cancer cells to survive and compromises the chemotherapeutical treatment. Therefore, the cell repair efficiency is substantial for the clinical outcome. High mobility group box 1 (HMGB1) protein is considered to be involved in the removal of the lesions as it binds with high affinity to cisplatin/DNA adducts. We demonstrated that overexpression of HMGB1 protein inhibited cis-platinated DNA repair in vivo and the effect strongly depended on its C-terminus. We registered increased levels of DNA repair after HMGB1 silencing only in p53 defective H1299 lung cancer cells. Next, introduction of functional p53 resulted in DNA repair inhibition. H1299 cells overexpressing HMGB1 were significantly sensitized to treatment with cisplatin demonstrating the close relation between the role of HMGB1 in repair of cis-platinated DNA and the efficiency of the anticancer drug, the process being modulated by the C-terminus. In A549 cells with functional p53, the repair of cisplatin/DNA adducts is determined by a complex action of HMGB1 and p53 as an increase of DNA repair capacity was registered only after silencing of both proteins. PMID- 26896490 TI - Coverage analysis in a targeted amplicon-based next-generation sequencing panel for myeloid neoplasms. AB - AIMS: PCR amplicon-based next-generation sequencing (NGS) panels are increasingly used for clinical diagnostic assays. Amplification bias is a well-known limitation of PCR amplicon-based approaches. We sought to characterise lower performance amplicons in an off-the-shelf NGS panel (TruSight Myeloid Sequencing Panel) for myeloid neoplasms and attempted to patch the low read depth for one of the affected genes, CEBPA. METHODS: We performed targeted NGS of 158 acute myeloid leukaemia samples and analysed the amplicon read depths across 568 amplicons to identify lower-performance amplicons. We also correlated the amplicon read depths with the template GC content. Finally, we attempted to patch the low read depth for CEBPA using a parallel library preparation (Nextera XT) workflow. RESULTS: We identified 16 lower-performance amplicons affecting nine genes, including CEBPA. There was a slight negative correlation between the amplicon read depths and template GC content. Addition of the separate CEBPA library generated a minimum read depth per base across the CEBPA gene ranging from 268x to 758x across eight samples. CONCLUSIONS: The identification of lower performance amplicons will be informative to laboratories intending to use this panel. We have also demonstrated proof-of-concept that different libraries (TruSight Myeloid and Nextera XT) can be combined and sequenced on the same flow cell to generate additional reads for CEBPA. PMID- 26896492 TI - VTE guideline weighs in on newer oral anticoagulants. PMID- 26896491 TI - The diagnosis of adult-onset haemophagocytic lymphohistiocytosis: lessons learned from a review of 29 cases of bone marrow haemophagocytosis in two large academic institutions. AB - AIMS: Haemophagocytic lymphohistiocytosis (HLH) is divided into paediatric (primary) and adult (secondary) types. While paediatric-HLH has been extensively characterised, similar studies in adults are limited. This study aims to evaluate the significance of the HLH diagnostic criteria as well as other clinical parameters in adults with bone marrow evidence of haemophagocytosis. METHODS: We conducted a 10-year retrospective search of the pathology archives of two institutions for cases with bone marrow haemophagocytosis. We included those cases that fulfilled the currently established HLH diagnostic criteria. For the 29 cases that met inclusion criteria, we assessed clinical features, co morbidities, therapy and clinical outcome. The effect of 19 clinical variables on mortality outcomes was assessed using logistic and hazard regression analyses. RESULTS: Of cases for which an aetiology could be identified, infectious diseases were the most common association (14 of 19, 74%). Fever and elevated ferritin were the most frequently available criteria used to establish HLH. The overall mortality rate was 61% despite HLH-specific therapy, which had been initiated in 48% of the cases. The remaining cases were treated with supportive therapy and antibiotics. The most statistically significant marker of mortality was an elevated absolute neutrophil count (ANC), a feature not typical of HLH. CONCLUSIONS: Since elevated ANC correlates with poor outcomes in sepsis, and not HLH, we postulate that many of the patients fulfilling HLH diagnostic criteria in this study likely had sepsis/systemic inflammatory response syndrome rather than HLH. Our results highlight the need to define HLH diagnostic criteria specific to the adult population. PMID- 26896493 TI - Ingestible sensor helps healthcare providers adjust antihypertensive regimens. PMID- 26896494 TI - Correction. PMID- 26896495 TI - Summaries of safety labeling changes approved by FDA-Boxed warnings highlights October-December 2015. PMID- 26896496 TI - Pharmacy leadership development through national resident collaboration. PMID- 26896497 TI - Implementation of active surveillance in electronic health records at pediatric institutions. PMID- 26896498 TI - Proctoring strategies for computer-based and paper-based tests. PMID- 26896499 TI - I.V. minocycline revisited for infections caused by multidrug-resistant organisms. AB - PURPOSE: The evidence supporting the potential use of i.v. minocycline for serious infections caused by multidrug-resistant organisms (MDROs) is summarized. SUMMARY: Minocycline achieves good tissue penetration and excellent oral absorption. Minocycline achieves serum concentrations comparable to other tetracyclines, with peak serum concentrations ranging from 3 to 8.75 mg/L following i.v. administration of 200 mg. Minocycline retains antimicrobial activity against methicillin-sensitive and methicillin-resistant Staphylococcus aureus as well as many gram-negative pathogens, such as Acinetobacter species, Citrobacter species, Enterobacter species, Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, and Stenotrophomonas maltophilia. Minocycline has been used to treat respiratory infections caused by Acinetobacter baumannii and bloodstream infections. The majority of these gram-negative infections were treated with combination therapy, with results similar to those seen with first line agents. The ability to switch from parenteral to oral therapy and its favorable tissue penetration make minocycline an attractive option for severe respiratory or skin and skin structure infections. For A. baumannii infections, minocycline is the second most active agent in vitro and may be the only therapeutic option in certain cases. The overall clinical experience with minocycline supports its use to treat A. baumannii infections alone or in combination with other agents. Minocycline could be used to treat other MDRO gram negative infections but only as an agent of last resort due to the limited data available. CONCLUSION: The available pharmacokinetic and clinical data support the use of i.v. minocycline for the treatment of MDRO infections, including infections due to S. aureus coagulase-negative and gram-negative pathogens. PMID- 26896500 TI - Probable doxycycline-induced acute pancreatitis. AB - PURPOSE: A probable case of doxycycline-induced pancreatitis is reported. SUMMARY: A 51-year-old man was admitted to the emergency department with a one week history of extreme fatigue, malaise, and confusion. Three days earlier he had been started on empirical doxycycline therapy for presumed Lyme disease; he was taking no other medications at the time of admission. A physical examination was remarkable for abdominal tenderness. Relevant laboratory data included a lipase concentration of 5410 units/L (normal range, 13-60 units/L), an amylase concentration of 1304 (normal range, 28-100 units/L), and a glycosylated hemoglobin concentration of 15.2% (normal, <5.7%). Tests for immunoglobulin G4, Lyme disease antibodies, influenza strains, human immunodeficiency virus, and hepatitis A, B, and C were all negative. Blood, urine, cerebrospinal fluid, and respiratory cultures showed no growth. Abdominal computed tomography findings were consistent with acute pancreatitis (AP). The patient was admitted to the intensive care unit and intubated, and doxycycline was discontinued. With vasopressor support, aggressive fluid resuscitation, hemodialysis, and an insulin infusion, the patient's clinical course rapidly improved over five days. Scoring of the case via the method of Naranjo et al. yielded a score of 6, indicating a probable adverse reaction to doxycycline. CONCLUSION: A man developed AP three days after starting therapy with oral doxycycline, and the association between drug and reaction was determined to be probable. His case appears to be the third of doxycycline-associated AP, although tigecycline, tetracycline, and minocycline have also been implicated as causes of AP. PMID- 26896501 TI - Converting U-500 regular insulin to insulin detemir and insulin lispro in a patient undergoing dietary changes in preparation for bariatric surgery. AB - PURPOSE: The safe and effective conversion of human regular U-500 insulin (U 500R) to basal and bolus U-100 (insulin detemir and insulin lispro, respectively) in a patient undergoing a significant dietary change in preparation for bariatric surgery is described. SUMMARY: Conversion from U-100 to U-500R insulin has been described in the literature. There is, however, a paucity of information describing the reverse conversion (i.e., from U-500R to U-100 insulin). Whether converting to or from U-500R, patient safety is a primary concern. A 51-year-old Caucasian woman with a 10-year history of type 2 diabetes mellitus, hypertension, and gastroparesis who was scheduled to undergo bariatric surgery was converted from U-500R to insulin detemir and insulin lispro preoperatively while undergoing significant diet changes. The patient's blood glucose values, diet, and activity levels were closely monitored daily by the interprofessional team over a 10-day preoperative period during which her regular diet was changed to a very low calorie, high-protein diet; insulin doses were adjusted accordingly. Throughout this process, the patient did not experience any major hypoglycemic episodes. Close collaboration among interprofessional team members and a strong partnership with the patient were considered key factors in the successful conversion of insulin therapy. CONCLUSION: Subcutaneous insulin therapy in a woman preparing for bariatric surgery was safely converted from U-500R to basal therapy with U 100 insulin detemir and with as-needed boluses of U-100 insulin lispro. This occurred as the patient switched from a regular diet to a low-calorie, high protein diet. PMID- 26896502 TI - Implementation of a penicillin allergy screening tool to optimize aztreonam use. AB - PURPOSE: The implementation of a penicillin allergy screening tool to optimize the use of aztreonam is described. METHODS: This study was conducted at a 528-bed tertiary referral community teaching facility and compared the use of aztreonam in patients before and after the implementation of a multipronged intervention consisting of a penicillin allergy screening tool (PAST), education, order set decision support, and prospective review of aztreonam orders by the antimicrobial stewardship team and clinical pharmacists. Patients for whom aztreonam was prescribed at any time during their presentation to the hospital January 1-June 30, 2013 (preintervention period), and September 1, 2013-February 28, 2014 (postintervention period) were eligible for inclusion. Primary outcomes included total and inappropriate aztreonam usage. Secondary outcomes included cost avoidance and safety. RESULTS: A total of 496 aztreonam orders were reviewed. The total number of days of therapy (DOT) with aztreonam significantly decreased from 9.5 per 1,000 patient-days in the preintervention group to 4.4 per 1,000 patient days in the postintervention group (p < 0.0001). The number of inappropriate aztreonam DOT decreased from 4.0 per 1,000 patient days to 0.8 per 1,000 patient days (p < 0.0001). The median number of inappropriate aztreonam doses decreased significantly in the postintervention period, as did inappropriate aztreonam DOT (p < 0.0001 for both comparisons). An estimated cost avoidance of $60,000 $100,000 was realized, depending on the alternative antibiotic selected. CONCLUSION: Implementation of the PAST and provider and pharmacist education reduced the use of aztreonam by promoting the first-line use of beta-lactam alternatives. PMID- 26896503 TI - A qualitative evaluation of medication management services in six Minnesota health systems. AB - PURPOSE: The initiation, establishment, and sustainability of medication management programs in six Minnesota health systems are described. METHODS: Six Minnesota health systems with well-established medication management programs were invited to participate in this study: Essentia Health, Fairview Health Services, HealthPartners, Hennepin County Medical Center, Mayo Clinic, and Park Nicollet Health Services. Qualitative methods were employed by conducting group interviews with key staff from each institution who were influential in the development of medication management services within their organization. Kotter's theory of eight steps for leading organizational change served as the framework for the question guide. The interviews were audio recorded, transcribed, and analyzed for recurring and emergent themes. RESULTS: A total of 13 distinct themes were associated with the successful integration of medication management services across the six healthcare systems. Identified themes clustered within three stages of Kotter's model for leading organizational change: creating a climate for change, engaging and enabling the whole organization, and implementing and sustaining change. The 13 themes included (1) external influences, (2) pharmacists as an untapped resource, (3) principles and professionalism, (4) organizational culture, (5) momentum champions, (6) collaborative relationships, (7) service promotion, (8) team-based care, (9) implementation strategies, (10) overcoming challenges, (11) supportive care model process, (12) measuring and reporting results, and (13) sustainability strategies. CONCLUSION: A qualitative survey of six health systems that successfully implemented medication management services in ambulatory care clinics revealed that a supportive culture and team-based collaborative care are among the themes identified as necessary for service sustainability. PMID- 26896504 TI - Comparison of telavancin and vancomycin lock solutions in eradication of biofilm producing staphylococci and enterococci from central venous catheters. AB - PURPOSE: Results of a study of the activity of antibiotic lock solutions of vancomycin and telavancin against biofilm-forming strains of Staphylococcus epidermidis, Enterococcus faecalis, and Staphylococcus aureus are reported. METHODS: An established in vitro central venous catheter model was used to evaluate lock solutions containing vancomycin (5 mg/mL) or telavancin (5 mg/mL), with and without preservative-containing heparin sodium (with 0.45% benzyl alcohol) 2500 units/mL, heparin, and 0.9% sodium chloride solution. Lock solutions were introduced after 24-hour bacterial growth in catheters incubated at 35 degrees C. After 72 hours of exposure to the lock solutions, catheters were drained, flushed, and cut into segments for quantification of colony-forming units. RESULTS: Against S. epidermidis, vancomycin and telavancin (with or without heparin) had similar activity. Against E. faecalis, vancomycin alone was more active than telavancin alone (p < 0.01). Against S. aureus, vancomycin plus heparin had activity similar to that of vancomycin alone; both lock agents had greater activity than telavancin (p < 0.02). The addition of heparin was associated with reduced activity of the vancomycin lock solution against S. epidermidis and E. faecalis (p < 0.01). Telavancin activity was not significantly changed with the addition of heparin. CONCLUSION: In a central venous catheter model, vancomycin and telavancin activity was similar in reducing biofilm producing S. epidermidis. However, vancomycin was more active than telavancin against E. faecalis and S. aureus. None of the tested agents eradicated biofilm forming strains. The addition of preservative-containing heparin sodium 2500 units/mL to vancomycin was associated with reduced activity against S. epidermidis and E. faecalis. PMID- 26896505 TI - Proportion of work appropriate for pharmacy technicians in anticoagulation clinics. AB - PURPOSE: Results of a two-part study to determine the proportion of anticoagulation clinic (AC) work that could potentially be shifted from a pharmacist to a clinical pharmacy technician (CPT) are presented. METHODS: In part 1 of the study, a group of eight clinical pharmacists and four CPTs from Veterans Affairs (VA) ACs used a modified Delphi process to categorize AC tasks as appropriate or inappropriate for a fully trained, licensed CPT. In part 2, a three-day time study was conducted at an AC staffed by one clinical pharmacist to determine the amounts of pharmacist time spent performing the tasks delineated through the Delphi process. Based on the time study data and task appropriateness categorizations, the proportion of AC work that might be appropriate for a CPT was estimated. RESULTS: Two levels of CPT-appropriate tasks were identified: those appropriate for any CPT and those appropriate only for an "advanced practice CPT"; the latter category of tasks included conducting follow-up phone interviews with patients found to have in-range International Normalized Ratio values. The results of the time study indicated that 21% of the AC workload could be handled by a CPT and 41% could be handled by an advanced-practice CPT. CONCLUSION: Investigation of AC roles within the VA system suggested that well trained pharmacy technicians can perform a substantial proportion of work in an AC, including some tasks performed by pharmacists. PMID- 26896506 TI - ASHP Statement on the Roles and Responsibilities of the Pharmacy Executive. PMID- 26896509 TI - The Impact of Leadership and Research on Decision Making: The Power of Knowledge. PMID- 26896507 TI - Parent Perceptions of Illness Uncertainty and Child Depressive Symptoms in Juvenile Rheumatic Diseases: Examining Caregiver Demand and Parent Distress as Mediators. AB - OBJECTIVE: Examine caregiver demand and general parent distress as mediators in the parent illness uncertainty-child depressive symptom association in youth with juvenile rheumatic diseases. METHODS: Children and adolescents completed the Child Depression Inventory; caregivers completed the Parent Perceptions of Uncertainty Scale, the Care for My Child with Rheumatic Disease Scale, and the Brief Symptom Inventory. The pediatric rheumatologist provided ratings of clinical disease status. RESULTS: Analyses revealed significant direct associations between illness uncertainty and caregiver demand, and between caregiver demand and both parent distress and child depressive symptoms. Results also revealed significant parent uncertainty -> caregiver demand -> parent distress and parent uncertainty -> caregiver demand -> child depressive symptom indirect paths. CONCLUSIONS: Results highlight the role of illness appraisals in adjustment to juvenile rheumatic diseases, and provide preliminary evidence that parent appraisals of illness uncertainty impact parent distress and child depressive symptoms indirectly through increased perceptions of caregiver demand. PMID- 26896508 TI - Factors associated with access to care and healthcare utilization in the homeless population of England. AB - Background: People experiencing homelessness are known to have complex health needs, which are often compounded by poor access to healthcare. This study investigates the individual-level factors associated with access to care and healthcare utilization among homeless people in England. Methods: A cross sectional sample of 2505 homeless people from 19 areas of England was used to investigate associations with access to care and healthcare utilization. Results: Rough sleepers were much less likely to be registered with a general practitioner (GP) (odds ratio (OR) 0.45, 95% confidence interval (CI) 0.30-0.66) than single homeless in accommodation (reference group) or the hidden homeless (OR 1.48, 95% CI 0.88-2.50). Those who had recently been refused registration by a GP or dentist also had lower odds of being admitted to hospital (OR 0.67, 95% CI 0.49 0.91) or using an ambulance (OR 0.73, 95% CI 0.54-0.99). Conclusions: The most vulnerable homeless people face the greatest barriers to utilizing healthcare. Rough sleepers have particularly low rates of GP registration and this appears to have a knock-on effect on admission to hospital. Improving primary care access for the homeless population could ensure that some of the most vulnerable people in society are able to access vital hospital services which they are currently missing out on. PMID- 26896510 TI - Interprofessional Collaboration between Dental Hygienists and Registered Nurses: The Time is Overdue. PMID- 26896511 TI - Parallels between the Development of the Nurse Practitioner and the Advancement of the Dental Hygienist. AB - PURPOSE: Dental hygienists have often been described as the registered nurses of the dental field. Similar parallels also exist between the development of the nurse practitioner from the nursing profession and the evolution of the dental hygiene practice and profession. This article explores 3 major similarities between the professions of nurse practitioner and dental hygienist. Public health issues, educational constructs, and the social and political environments shaping each profession are discussed to inform dental hygienists of their potential career options for future expanded therapeutic care roles. PMID- 26896512 TI - The Frequency of Dietary Advice Provision in a Dental Hygiene Clinic: A Retrospective Cross-Sectional Study. AB - PURPOSE: The aim of this retrospective, cross-sectional study was to assess the frequency of dietary advice provision by dental hygiene students. METHODS: Data was obtained from clinical records of third-year Bachelor of Oral Health students at the University of Newcastle. Frequency of dietary advice was recorded by students over a 12-month period. The study investigated associations between demographics, treatment provided and frequency of dietary advice. RESULTS: The results indicated dietary advice was provided infrequently by dental hygiene students, with only 6.48% of all patients seen during the 12-month period receiving dietary advice. A statistically significant correlation was observed between dietary advice and age, with children under the age of 18 being 2.5 times more likely than adults to receive dietary advice. Additionally, patients who received oral hygiene instruction were 2.5 times as likely to receive dietary advice. Strong correlations were also observed between topical and concentrated fluoride application and dietary advice. CONCLUSION: The findings indicate dietary advice is provided infrequently by dental hygiene students. Further research is required to strengthen the findings and to investigate barriers to dietary advice provision, as well as perceptions of dental practitioners regarding dietary advice. PMID- 26896513 TI - Association between Early Childhood Caries, Feeding Practices and an Established Dental Home. AB - PURPOSE: Early Childhood Caries (ECC) is a significant public health concern disproportionately affecting low-income children. The purpose of this study was to assess the association between the establishment of a dental home and ECC prevalence in a group of Medicaid-enrolled preschool children, and to explore feeding practices associated with an increased prevalence of ECC in Medicaid enrolled preschool children with an established dental home was evaluated. METHODS: A cross-sectional survey was conducted among Medicaid-enrolled children (n=132) between 2 and 5 years of age with an established dental home and no dental home to compare feeding practices, parental knowledge of caries risk factors and oral health status. RESULTS: Children with an established dental home had lower rates of biofilm (p<0.05), gingivitis (p<0.05) and mean decayed, missing and filled teeth (DMFT) scores (p<0.05). Children with no dental home consumed more soda and juice (p<0.05) daily, and ate more sticky fruit snacks (p<0.05) than children with an established dental home. Establishment of a dental home had a strong protective effect on caries and DMFT index (odds ratio=0.22) in both univariate and confounding adjusted analyses. CONCLUSION: The results suggest establishment of a dental home, especially among high-risk, low-income populations, decreases the prevalence of ECC and reduces the practice of cariogenic feeding behaviors. PMID- 26896514 TI - Readability Levels of Dental Patient Education Brochures. AB - PURPOSE: The objective of this study was to evaluate dental patient education brochures produced since 2000 to determine if there is any change in the Flesch Kincaid grade level readability. METHODS: A convenience sample of 36 brochures was obtained for analysis of the readability of the patient education material on multiple dental topics. Readability was measured using the Flesch-Kincaid Grade Level through Microsoft Word. Pearson's correlation was used to describe the relationship among the factors of interest. Backward model selection of multiple linear regression model was used to investigate the relationship between Flesch Kincaid Grade level and a set of predictors included in this study. RESULTS: A convenience sample (n=36) of dental education brochures produced from 2000 to 2014 showed a mean Flesch-Kincaid reading grade level of 9.15. Weak to moderate correlations existed between word count and grade level (r=0.40) and characters count and grade level (r=0.46); strong correlations were found between grade level and average words per sentence (r=0.70), average characters per word (r=0.85) and Flesch Reading Ease (r=-0.98). Only 1 brochure out of the sample met the recommended sixth grade reading level (Flesch-Kincaid Grade Level 5.7). Overall, the Flesch-Kincaid Grade Level of all brochures was significantly higher than the recommended sixth grade reading level (p<0.0001). CONCLUSION: The findings from this study demonstrated that there has generally been an improvement in the Flesch-Kincaid grade level readability of the brochures. However, the majority of the brochures analyzed are still testing above the recommended sixth grade reading level. PMID- 26896515 TI - Analysis of Phone Calls Regarding Fluoride Exposure made to New Jersey Poison Control Center from 2010 to 2012. AB - PURPOSE: The American Association of Poison Control Center's annual reports demonstrate that acute fluoride exposure is not an uncommon occurrence. Despite its prevalence, there has been little published research on the topic in the last 10 years. The purpose of this study was to calculate the incidence of acute fluoride toxicity and lethality as it occurs in New Jersey and provide a descriptive epidemiology of acute fluoride exposures. METHODS: The study design was retrospective in nature. Records of phone calls made by individuals reporting excessive fluoride exposure (in an amount greater than directed/prescribed) to New Jersey's poison control center, known as Poison Information and Education System from the years 2010 through 2012, were extracted from Toxicall(r) (Computer Automatic Systems, Inc.) database. A total of 2,476 human-only exposure records met the inclusion criteria and were analyzed. Incidence rates were calculated, and population characteristics, circumstances and medical outcomes of acute fluoride exposure cases were assessed and categorized. RESULTS: A total of 2,476 phone call records met the inclusion criteria. The fluoride exposures reported were from toothpaste with fluoride (49%, n=1,214), mouth rinse with fluoride (21.6%, n=536), multivitamin with fluoride (21.4%, n=530) and pure fluoride (0.08%, n=199). Medically speaking, 94.75% of calls were asymptomatic cases (n=2,346), 4.24% were symptomatic (n=105) and 1.01% were informational inquiries (n=25). Adverse symptoms reported were mostly minor (83.9% of symptomatic cases, n=88) and moderate (16.1% of symptomatic cases, n=17). The age group 18 months to 3 years of age showed the highest incidence of acute fluoride exposure (53.2%, n=1,317). There was a slightly higher incidence of acute fluoride exposures among males (n=1,317) vs. females (n=1,159). Most incidences occurred in the home (93.1% of records, n=2,305) and occurred unintentionally (96.7%, n=2,394). Calls were mainly made by the subject's mother (67.5%, n=1,671). CONCLUSION: Based on the data, there were no reports of lethality or toxicity due to acute fluoride exposure in New Jersey from 2010 through 2012. Symptomatic reports and informational inquiries were few. All adverse outcomes due to excessive fluoride intake were remedied with calcium as the antidote. Dental hygienists should educate patients on safety measures of fluoride containing products and evaluate overall fluoride exposure prior to making recommendations. However, findings in this study suggest that levels of fluoride in available commercial products will not produce life-threatening events, even if taken in doses higher than recommended. PMID- 26896517 TI - Assessing Faculty Development Needs among Florida's Allied Dental Faculty. AB - PURPOSE: Professional schools rarely prepare prospective academic faculty for the responsibilities of college and university teaching. Without this training, faculty are often left to discover on their own and to varying degrees of success what is expected of them once they enter the academy. At the same time, universities and colleges recognize that retention of faculty depends on the successful transition of academics into the related roles and responsibilities of the professoriate. The purpose of this study was to assess the faculty development needs among allied dental faculty, specifically the state of Florida's dental hygiene and dental assisting faculty, by measuring the following: the relationship between their knowledge and priorities for further training, their level of satisfaction with current faculty development opportunities and mentoring, and their perceptions of what additional training and resources might advance their careers. METHODS: Two hundred and four full time and part-time faculty were invited to participate in this survey research study. McNemar's test for paired binary data was used to analyze the level of agreement between knowledge and indicated priority. Responses to open ended questions were coded and categorized thematically. RESULTS: There were 115 responses (n=204, 74%). There were statistically significant differences between participants' ratings of knowledge and priorities for further training on many items related to teaching, scholarship and leadership skills. Participants also identified 5 categories of unmet needs. CONCLUSION: The findings suggest that universities and colleges need to offer learning experiences aimed at strengthening the teaching, scholarship and leadership skill needs of their allied dental faculty. Additionally, professional schools might consider offering a program track that provides prospective allied dental faculty with the types of opportunities that develops teaching, scholarship and mentoring skills prior to graduation. PMID- 26896516 TI - Effect of a Simulation Exercise on Restorative Identification Skills of First Year Dental Hygiene Students. AB - PURPOSE: This study explored the effectiveness of simulated mouth models to improve identification and recording of dental restorations when compared to using traditional didactic instruction combined with 2-dimensional images. Simulation has been adopted into medical and dental education curriculum to improve both student learning and patient safety outcomes. METHODS: A 2-sample, independent t-test analysis of data was conducted to compare graded dental recordings of dental hygiene students using simulated mouth models and dental hygiene students using 2-dimensional photographs. Evaluations from graded dental charts were analyzed and compared between groups of students using the simulated mouth models containing random placement of custom preventive and restorative materials and traditional 2-dimensional representations of didactically described conditions. RESULTS: Results demonstrated a statistically significant (p<=0.0001) difference: for experimental group, students using the simulated mouth models to identify and record dental conditions had a mean of 86.73 and variance of 33.84. The control group students using traditional 2-dimensional images mean graded dental chart scores were 74.43 and variance was 14.25. CONCLUSION: Using modified simulation technology for dental charting identification may increase level of dental charting skill competency in first year dental hygiene students. PMID- 26896518 TI - Clinical Practice Guidelines for Recall and Maintenance of Patients with Tooth Borne and Implant-Borne Dental Restorations. AB - PURPOSE: To provide guidelines for patient recall regimen, professional maintenance regimen, and at-home maintenance regimen for patients with tooth- and implant-borne removable and fixed restorations. METHODS: The American College of Prosthodontists (ACP) convened a scientific panel of experts appointed by the ACP, American Dental Association (ADA), Academy of General Dentistry (AGD), and American Dental Hygienists Association (ADHA) who critically evaluated and debated recently published findings from 2 systematic reviews on this topic. The major outcomes and consequences considered during formulation of the clinical practice guidelines (CPGs) were risk for failure of tooth- and implant-borne restorations. The panel conducted a round table discussion of the proposed guidelines, which were debated in detail. Feedback was used to supplement and refine the proposed guidelines, and consensus was attained. RESULTS: A set of CPGs was developed for tooth-borne restorations and implant-borne restorations. Each CPG comprised of 1) patient recall; 2) professional maintenance, and 3) at home maintenance. For tooth-borne restorations, the professional maintenance and at-home maintenance CPGs were subdivided for removable and fixed restorations. For implant-borne restorations, the professional maintenance CPGs were subdivided for removable and fixed restorations and further divided into biological maintenance and mechanical maintenance for each type of restoration. The at-home maintenance CPGs were subdivided for removable and fixed restorations. CONCLUSION: The clinical practice guidelines presented in this document were initially developed using the 2 systematic reviews. Additional guidelines were developed using expert opinion and consensus, which included discussion of the best clinical practices, clinical feasibility and risk-benefit ratio to the patient. To the authors' knowledge, these are the first CPGs addressing patient recall regimen, professional maintenance regimen, and at-home maintenance regimen for patients with tooth-borne and implant-borne restorations. This document serves as a baseline with the expectation of future modifications when additional evidence becomes available. PMID- 26896519 TI - The determinants of transitions into sheltered accommodation in later life in England and Wales. AB - BACKGROUND: Population ageing is a global challenge and understanding the dynamics of living arrangements in later life and their implications for the design of appropriate housing and long-term care is a critical policy issue. Existing research has focused on the study of transitions into residential care in the UK. This paper investigates transitions into sheltered accommodation among older people in England and Wales between 1993 and 2008. METHODS: The study uses longitudinal data constructed from pooled observations across waves 2-18 of the British Household Panel Survey (BHPS) data, focusing on individuals aged 65 and over who lived in private housing at baseline and who were observed for two consecutive time points. A discrete-time logistic regression model was used to examine the association of transitioning into sheltered accommodation with a range of demographic, health and socioeconomic predictors. RESULTS: Demographic (age, region), socioeconomic factors (housing tenure, having a washing machine) and contact with health professionals (number of visits to the general practitioner, start in use of health visitor) were significant determinants of an older person's move into sheltered accommodation. CONCLUSIONS: Transitions into sheltered accommodation are associated with a range of demographic and socioeconomic characteristics as well as service use but not with health. Such results indicate that this type of housing option may be accessible by individuals with relatively good health, but may be limited to those who are referred by gatekeepers. Policymakers could consider making such housing option available to everyone, as well as providing incentives for building lifecourse sensitive housing in the future. PMID- 26896520 TI - Pharmacists' role in a hospital's initiative to become a certified primary stroke center. AB - PURPOSE: Significant pharmacy department contributions to a medical center's efforts to attain certification as a primary stroke center (PSC) are described. SUMMARY: As part of an initiative to improve outcomes in patients with stroke and earn the PSC designation, the pharmacy department of an 855-bed community teaching hospital participated in developing a multifaceted "Code Stroke" program. Pharmacists deployed in the emergency department (ED), intensive care units, and medical units are involved in all aspects of stroke care from admission to discharge. Pharmacists attend ED responses to Code Stroke alerts, assisting in patient evaluation and helping to ensure timely tissue plasminogen activator (t-PA) administration and prompt computed tomography scanning. Throughout the hospital stay of a patient with stroke, pharmacists are involved in verifying that applicable Joint Commission core measures are met. Once a patient with stroke is deemed ready for discharge, a transitions-of-care pharmacist ensures that the patient receives the assistance necessary to obtain newly prescribed medications and counseling to promote postdischarge compliance. Implementation of the Code Stroke program was associated with improvements in stroke care quality measures, including a reduction in the median time from hospital arrival to t-PA administration and improved core measure compliance. CONCLUSION: By participating in the implementation of a number of transformative initiatives, the pharmacy department played an important role in enabling the medical center to provide consistent, excellent care for all patients with stroke as it prepared for certification as a PSC. PMID- 26896521 TI - Voriconazole concentration monitoring at an academic medical center. AB - PURPOSE: Results of a study of the relationship among voriconazole dosages, serum concentrations, adverse effects, and clinical outcomes are presented. METHODS: A retrospective chart review was conducted that included all patients who had at least one voriconazole concentration drawn between July 1, 2009, and August 15, 2014, at a single academic medical center. The primary outcome was the proportion of patients with initial voriconazole concentrations in the target range. RESULTS: Forty-seven of 88 patients (53%) had an initial voriconazole concentration within the target range, 27% (24 of 88) of patients had a concentration above the range, and 19% (17 of 88) had a concentration below the range. Sixty-seven percent of patients with above-target concentrations had adverse effects. Voriconazole was discontinued in 9% of patients, and dosages were reduced in 11% of patients because of adverse effects. Voriconazole for treatment versus prophylaxis was analyzed in a subgroup, as was obesity and nonobesity. Twenty-four percent of patients died during their hospital admission, and 14% were not discharged on voriconazole therapy. The within-target group had the highest proportion of patients discharged on voriconazole and the lowest proportion of deaths. CONCLUSION: A retrospective study in one institution revealed that the first measured voriconazole concentration was within the target range in 53% of patients and that dosage was modified in only 51% of patients whose concentration was outside of that range. The majority of patients with above-target concentrations had an adverse effect, and this result was particularly common in patients with a body mass index of >=35 kg/m(2). PMID- 26896522 TI - Assessment of low-dose i.v. ketamine infusions for adjunctive analgesia. AB - PURPOSE: The results of a study evaluating all patients treated with adjunctive low-dose ketamine for analgesia over a three-year period are presented. METHODS: A retrospective single-center analysis evaluated all adult patients who received adjunctive low-dose i.v. ketamine infusions from September 2010 to September 2013. Patients were excluded if they received concomitant oral ketamine, if ketamine was used to treat seizures, or if the patients received ketamine boluses without infusion. The primary endpoint was to identify the patient populations receiving low-dose intravenous ketamine. Secondary endpoints included an assessment of clinical variables and adverse events. Demographic information, level of care, clinical variables, adverse events, and patient outcomes were recorded. RESULTS: A total of 460 patients were evaluated. Of these, 396 were included in this analysis. Ketamine was administered to 69.9% of the patients in association with a surgical procedure, as opposed to 30.1% who received ketamine for medical management of pain. The percentage of patients receiving intensive care unit level care was 24%. Before initiation of ketamine, patient-reported pain scores averaged 7.1 +/- 2.63 S.D.; during the ketamine infusion, patient reported pain scores averaged 6.42 +/- 2.01 S.D.; (p < 0.001). In the safety analysis, hypertension occurred in 21.4% of patients, hypotension occurred in 15.1% of patients, and respiratory depression occurred in 6.3% of patients. CONCLUSION: A retrospective review found that patients receiving continuous ketamine infusions in addition to opioid therapy saw a reduction in pain scores and experienced cardiovascular adverse effects in greater than 20% of cases. PMID- 26896523 TI - Treatment of dyslipidemia with statins by primary care providers in Veterans with and without chronic Hepatitis C. AB - OBJECTIVE: The purpose of this study was to describe the current use of statins in United States (US) veterans at W. G. Hefner Veterans Affairs Medical Center (VA Salisbury) with chronic hepatitis C virus (HCV) compared to those without chronic HCV and to examine why statin use may be avoided in this population. METHODS: In this retrospective chart review, eligible participants were veterans enrolled in VA Salisbury primary care services who were at least 18 years of age with a diagnosis of dyslipidemia. Veterans must have had a lipid panel drawn between April 25, 2011 and October 25, 2011. The primary outcome of this study was to determine the prevalence of statin use among US veterans with HCV. A secondary outcome was to determine the proportion of subjects reaching goal LDL levels. RESULTS: A total of 157 subjects were included in this study. A significant difference in statin use was seen between subjects with and without HCV (54% vs. 83%, p <0.001). Although there were a greater number of subjects on statins in the non-HCV group, there was not a significant difference in the proportion of subjects reaching their LDL goal between the two groups. CONCLUSION: Among veterans, statins are used less frequently in patients with HCV compared to those without HCV. Both groups had similar achievement of LDL goals, though. PMID- 26896524 TI - Medication utilization evaluation of dabigatran and rivaroxaban within a large, multi-center health system. AB - OBJECTIVE: The objective of this medication utilization evaluation (MUE) was to determine the appropriateness of dabigatran and rivaroxaban while also reviewing outcomes for safety and effectiveness within a large, multi-center health system. METHODS: A retrospective chart review was performed using the system's electronic medical record. A data inquiry was requested and generated for dabigatran usage from July 28, 2011 through July 28, 2012 and for rivaroxaban from March 1, 2012 to July 31, 2012 at eight health system hospitals. All patients receiving at least one dose were eligible for inclusion in the MUE. RESULTS: For dabigatran, 78 of 390 unique patient encounters were analyzed (20%). All 62 rivaroxaban encounters were included in the analysis. Dabigatran was used for appropriate indications in 94% of encounters and 82% for rivaroxaban. Based on indication and renal function, 87% of dabigatran patients and 92% of rivaroxaban patients received correct dosing. For patients transitioning to or from another anticoagulant, appropriate transitions occurred in 44% of dabigatran transitions and 48% of rivaroxaban transitions. At discharge, 83% of dabigatran and 86% of rivaroxaban therapy was continued. There were no reported strokes or systemic embolism with dabigatran, but one reported deep vein thrombosis occurred during hospitalization with rivaroxaban therapy. Documented bleeds in 5% of dabigatran and 3% of rivaroxaban patients. Patient education was documented for 37% of dabigatran and 26% of rivaroxaban patients receiving therapeutic anticoagulation. CONCLUSION: This MUE revealed the appropriate use of dabigatran and rivaroxaban therapy with few safety outcomes within a large, multi-center health system. PMID- 26896525 TI - Observations of resistance through minimum inhibitory concentrations trends for respiratory specimens of commonly isolated organisms. AB - OBJECTIVE: The objective of this study was to determine minimum inhibitory concentration (MIC) trends among common bacterial organisms found in respiratory isolates in the trauma intensive care unit setting. METHODS: In this retrospective observational study, MIC data was reviewed over a three year period from January 2009 to December 2011 for the three most frequently identified organisms isolated from respiratory specimens in a trauma intensive care unit along with corresponding hospital data. RESULTS: The most frequently isolated bacterial species identified were Staphylococcus aureus (229 isolates), Pseudomonas aeruginosa (129 isolates), and Acinetobacter species (87 isolates) in the analysis within our institution from 2009-2011. There was considerable variability among the MIC trends for the analyzed organisms. For Pseudomonas isolates, observed sensitivities were as high as 100% for antibiotics ciprofloxacin and imipenem in 2009, but decreased over the next two years in 2010 and 2011. There was considerable variability among the MIC trends for Acinetobacter over the three year period for the antibiotics tested. The MIC data for most Staphylococcus aureus isolates over the three years were sensitive to vancomycin with little change in the observed MIC data. CONCLUSION: The data reported is observational and indicates the need for future studies to establish a valid relationship of the MIC data over time in our institution particularly among our gram negative organisms, to monitor patterns of antimicrobial resistance. PMID- 26896526 TI - Pharmacist-driven antimicrobial optimization in the emergency department. AB - PURPOSE: A pharmacist-driven antimicrobial optimization service in the non-trauma emergency department (ED) of an 864-bed non-profit tertiary care teaching hospital was reviewed to assess its value. Local antimicrobial resistance patterns of urine, wound, stool, and blood cultures were also studied to determine whether or not empiric prescribing practices should be modified. METHODS: A retrospective electronic chart review was performed for ED patients with positive cultures during two different three-month periods. During Period 1, ED nursing management performed positive culture follow-up. During Period 2, ED clinical pharmacists performed this role. The primary objective was to determine the value of the pharmacist-driven antimicrobial optimization service as measured by the number of clinical interventions made when indicated. The secondary objective was to examine resistance patterns of urine and wound isolates in order to determine if empiric prescribing patterns in the ED should be modified. RESULTS: During Period 1, there were 499 patient visits with subsequent positive cultures. Of those, 76 patients (15%) were discharged home. Nursing management intervened on 21 of 42 (50%) positive cultures that required an intervention; in Period 2, there were 473 patient visits with subsequent positive cultures, and 64 (14%) were discharged home. Pharmacists intervened on 24 of 30 (80%) cultures where an intervention was indicated resulting in a 30% increase in interventions for inappropriate therapy (p = 0.01). A review of the secondary objective revealed a 38% fluoroquinolone resistance rate of E. coli, the most frequently isolated urinary organism. CONCLUSION: Pharmacist-driven antimicrobial stewardship program resulted in a 30% absolute increase in interventions for inappropriate therapy as compared to the nursing-driven model. This stewardship program has further demonstrated the value of ED pharmacists. Pharmacist interventions should help to ensure that infections are resolved through modification of antimicrobial therapies for patients with bug-drug mismatches. The fluoroquinolone resistance rate indicates a need to consider alternative therapies for uncomplicated urinary tract infections. Nitrofurantoin remains with good coverage against E. coli and Enterococcus species but should be used in uncomplicated patients with normal renal function. PMID- 26896527 TI - Evaluation of an inpatient psychiatric hospital physician education program and adherence to American Diabetes Association practice recommendations. AB - OBJECTIVE: This study evaluated adherence to American Diabetes Association (ADA) recommendations for diabetes monitoring following an educational intervention for physicians in an inpatient psychiatric hospital. METHODS: This retrospective chart review was conducted in an inpatient psychiatric institution from July 1, 2010-January 15, 2011. A total of 120 subjects (60 subjects each in the pre- and post-intervention groups) meeting the inclusion criteria served as the study sample. Included subjects were admitted and discharged from an inpatient psychiatric institution within 90 days prior to (pre-intervention) and following (post-intervention) the physician education program. The medical staff was presented an educational program intervention, consisting of a 30 minute overview of the ADA 2010 Standards of Care recommendations and distribution of laminated treatment reminders. Electronic grouped order sets for patients with diabetes were also created and implemented. RESULTS: The primary outcome was change (pre intervention to post-intervention) in frequency of hemoglobin A1c documentation on admission following the intervention. Secondary outcomes included the change in frequency of documentation of fasting plasma glucose, serum creatinine, urine creatinine/microalbumin ratio (UMA), fasting lipid profile (FLP), and change in days on sliding scale insulin. Regarding change in frequency of documentation of A1c values on admission, chi-square analysis revealed a significant increase from pre-intervention to post-intervention period of 30% (n = 18) to 61.7% (n = 37), respectively (p = 0.0005). Documentation of FLP also significantly increased [73.3% vs. 91.7% (p = 0.0082)]. There were no significant differences in the documentation of fasting plasma glucose, serum creatinine, and UMA or days treated with sliding scale insulin. CONCLUSION: The physician education program was successful in increasing the assessment of A1c values and lipid profiles for patients with diabetes mellitus in a psychiatric institution. PMID- 26896528 TI - Achieving cholesterol goals with low-cost 3-hydroxy-3-methylglutaryl coenzyme-A (HMG Co-A) reductase inhibitors. AB - OBJECTIVE: The objective of this study was to determine the efficacy of widely available low-cost generic statins in achieving NCEP/ATP III cholesterol goals in diabetic patients seen in an indigent clinic. METHODS: Retrospective chart review of patients seen in the pharmacist managed diabetes clinic between January 1, 2005 and February 10, 2010. 154 patient charts were reviewed, with 12 included for analysis. Patients were age >40, diagnosed with diabetes mellitus, referred to the pharmacy clinic for diabetes management, and treated with a study statin for 6 weeks. Patients were excluded for baseline triglycerides >400 mg/dL, treatment with a non-study lipid lowering therapy <=6 weeks prior to baseline, or pregnancy. The primary endpoint was the proportion of patients with an LDL <100 mg/dL at 6 weeks. Secondary endpoints included an LDL <70 mg/dL, other cholesterol goals, and a 30% reduction in LDL at 6 weeks. RESULTS: At the first follow-up, 33% (n = 4) of patients achieved an LDL <100 mg/dL, and 66.7% (n = 8) a 30% LDL reduction. Race was a significant predictor, with Caucasians having greater LDL reductions than non-Caucasians at 6 weeks (Pearson Correlation 0.595, p = 0.041). Higher doses were significant predictors of greater change in LDL (Pearson Correlation -0.708, p = 0.01). CONCLUSION: Due to the small sample size, statistical power was not met. Both race and dose were significant predictors of LDL reduction. When controlled for race, dose remained a significant predictor of LDL reduction. Further studies with low-cost statins in a larger patient population are needed. PMID- 26896529 TI - Impact of a pharmacist-driven warfarin management protocol on achieving therapeutic International Normalized Ratios. AB - OBJECTIVE: Warfarin is a high alert medication and a challenge to dose and monitor. Pharmacist-driven warfarin management has been shown to decrease the time international normalized ratio (INR) is out of range, which may reduce undesired outcomes. The purpose of this study is to assess the effect of the implementation of a pharmacist-driven warfarin management protocol on the achievement of therapeutic INRs. METHODS: A warfarin management protocol was developed using evidence based literature and similar protocols from other institutions. Pharmacists utilized the protocol to provide patient specific warfarin dosing upon provider referral. To evaluate the protocol's impact, a retrospective chart review pre- and post-implementation was completed for admitted patients receiving warfarin. RESULTS: Three hundred twenty-seven charts were reviewed for pre- and post-implementation data. INRs within therapeutic range increased from 27.8% before protocol implementation to 38.5% after implementation. There was also a reduction in subtherapeutic INRs (55.3% pre to 39% post) and supratherapeutic INRs 5 or above (3.7% pre to 2.6% post). Supratherapeutic INRs between 3 and 5 did increase from 13.2% before protocol implementation to 19.9% in the pharmacist managed group. In addition to reducing the time to achievement of therapeutic INRs by 0.5 days, implementation of the protocol resulted in an increased the number of patients with at least one therapeutic INR during admission (35% pre to 40% post). CONCLUSION: The implementation of a pharmacist-driven warfarin dosing protocol increased therapeutic INRs, and decreased the time to therapeutic range, as well as the proportion of subtherapeutic INRs and supratherapeutic INRs 5 or greater. Additional benefits of the protocol include documentation of Joint Commission National Patient Safety Goal compliance, promotion of interdisciplinary collaboration and increased continuity of care. PMID- 26896530 TI - Impact of an antimicrobial stewardship initiative to evaluate beta-lactam allergy in patients ordered aztreonam. AB - PURPOSE: An evaluation of the clinical and economic impact of an antimicrobial stewardship quality initiative (ASQI) focusing on allergy assessment in patients with a documented beta-lactam allergy prescribed aztreonam was conducted. METHODS: This retrospective study was executed at a hospital with an interdisciplinary antimicrobial stewardship program (ASP). A total of 186 patients with self-reported beta-lactam allergies who were prescribed aztreonam while admitted during a 36-month time period surrounding the ASQI implementation were included. The primary study outcome was median time in hours to aztreonam discontinuation among nonanaphylactic patients. RESULTS: After implementation of the ASQI, the percentage of patients continued on aztreonam for the duration of therapy was nearly cut in half, and a greater percentage of patients were switched to beta-lactam antibiotics. No adverse effects associated with beta lactam therapy were observed in any study patient. Antimicrobial cost savings was not associated with any difference in clinical outcomes. Overall, hospitalwide aztreonam prescribing and aztreonam use declined. Institutional aztreonam orders per 1000 patient-days decreased from 1.5 to 1 after implementation of the ASQI. Additionally, hospitalwide aztreonam days of therapy per 1000 patient-days was reduced from 3.6 in the pre-ASQI period to 1.8 in the post-ASQI period. CONCLUSION: An ASQI that included critical evaluation of patient-reported beta lactam allergies led to decreased aztreonam use, reduced antimicrobial expenditure, and similar clinical outcomes to those observed before implementation. PMID- 26896531 TI - Dynamic filling parameters in patients with atrial fibrillation: differentiating rhythm induced from ventilation-induced variations in pulse pressure. AB - In patients with sinus rhythm, the magnitude of mechanical ventilation (MV) induced changes in pulse pressure (PP) is known to predict the effect of fluid loading on cardiac output. This approach, however, is not applicable in patients with atrial fibrillation (AF). We propose a method to isolate this effect of MV from the rhythm-induced chaotic changes in PP in patients with AF. In 10 patients undergoing pulmonary vein ablation for treatment of AF under general anesthesia, ECG and PP waveforms were analyzed during apnea (T1) and during MV at tidal volumes of 8 ml/kg (T2) and 12 ml/kg (T3), respectively. In a first step, three mathematical models were compared in their ability to predict individual PP at T1. The best-fitting model was then selected as the reference to quantify the effects of MV on PP in these patients. A local polynomial regression model based on two preceding RR intervals (LOC2) was found to be superior over the quadratic models to predict PP. LOC2 was therefore selected to quantify variations in PP induced by MV. During T2 and T3, magnitude of PP deviations was related with the amplitude of tidal volume [mean bias error (SD) of -5 (6) and -8 (7) mmHg for T2 and T3, respectively; P = 0.003 repeated-measures ANOVA]. We conclude that LOC2 most accurately predicted rhythm-induced variations in PP. MV-induced deviations in PP can be quantified and may therefore provide a method to study cardiopulmonary interactions in the presence of arrhythmia. PMID- 26896532 TI - The Effect of Western Corn Rootworm (Coleoptera: Chrysomelidae) and Water Deficit on Maize Performance Under Controlled Conditions. AB - The western corn rootworm, Diabrotica virgifera virgifera LeConte, is the most important insect of maize, Zea mays L., but knowledge of its interaction with water deficit on maize production is lacking. A series of greenhouse experiments using three infestation levels of the western corn rootworm, D. virgifera virgifera, under well-watered, moderately dry, and very dry soil moisture levels were conducted to quantify the interaction of western corn rootworm and soil water deficit on B73*Mo17 maize growth and physiology. Three separate experiments were conducted. Soil moisture regimes were initiated 30 d postplanting for experiments using neonate and second-instar larvae and 30 d postinfestation in the experiment using eggs. In the neonate and second-instar experiments, there were no significant differences among western corn rootworm levels in their effects on leaf water potential, shoot dry weight, and root dry weight. The interaction of western corn rootworm and soil moisture significantly impacted the larval recovery in the neonate experiment, but no other significant interactions were documented between soil moisture levels and rootworm infestation levels. Overall, the results indicate that under the conditions of these experiments, the effect of water deficit was much greater on plants than the effect of western corn rootworm and that the interactions between water deficit and western corn rootworm levels minimally affected the measured parameters of plant performance. PMID- 26896533 TI - Megacopta cribraria (Hemiptera: Plataspidae) Population Dynamics in Soybeans as Influenced by Planting Date, Maturity Group, and Insecticide Use. AB - Since its unintentional introduction during 2009, Megacopta cribraria (F.) has spread rapidly throughout the southeastern United States, mainly feeding and reproducing on kudzu, Pueraria montana Loureiro (Merr.) variety lobata (Willdenow), and soybeans, Glycine max (L.) Merr. Megacopta cribraria has become a serious economic pest in soybeans, forcing growers to rely solely on insecticide applications to control this insect. The main objective of this study was to investigate if variation in planting date and maturity group of soybeans had an impact on management of M. cribraria populations. Three experimental fields were located in North Carolina (2) and South Carolina (1), and the tests replicated during 2012 and 2013. Treatments consisted of three planting dates, four maturity groups, and insecticide treated versus untreated, at each location. More M. cribraria were found in untreated early planted soybeans than late planted soybeans. Generally, maturity group did not influence population densities of M. cribraria. Yield was significantly influenced by the interaction between planting date and maturity group. There was a negative linear relationship between M. cribraria populations and soybean yield. Although early planted soybeans may avoid drought conditions and potentially large populations of defoliators, these fields may be at greater risk for infestation by M. cribraria. PMID- 26896534 TI - Digestion of Termiticide Bait Matrices by the Pest Termite Reticulitermes flavipes (Isoptera: Rhinotermitidae). AB - Termites are highly effective digesters of wood lignocellulose, which is a central factor contributing to their global status as pests of wooden structures. For the same reason, termite baits that combine cellulosic matrices with slow acting insecticides are both effective and popular as a reduced-risk approach for termite control. This study took a novel approach for assessing digestibility of termite bait matrices and matrix components to gain potentially new insights into bait attractiveness and efficacy. The rationale behind this study is that termite baits that are more digestible should have more nutritional value to termites and thus encourage maximal feeding and trophallactic transfer of active ingredients through termite colonies. Studies were done using in vitro digestion assays with termite gut protein extracts followed by colorimetric detection of released glucose and pentose monosaccharides from test substrates. The substrates tested included two commercial bait matrices (Recruit IV and Recruit II HD), two matrix components (compressed and toasted compressed cellulose), and two natural pine woods as positive controls (southern yellow and northern pine). Overall results show equal or greater monosaccharide availability for some commercial matrices than standard pine lignocelluloses, suggesting sufficient nutritional value for the proprietary matrices. Another more prominent trend was significant intercolony variation in digestibility across substrates, possibly resulting from differences in microbiota composition, long-term diet adaptation, or both. These findings thus illuminate new nutrition-based factors that can potentially impact bait feeding, trophallactic exchange, and efficacy. PMID- 26896535 TI - Reinvasion Dynamics of Subterranean Termites (Isoptera: Rhinotermitidae) Following the Elimination of All Detectable Colonies in a Large Area. AB - Following the elimination of all detectable termite colonies in the 32-acre Louis Armstrong Park in New Orleans, LA, in 2002-2003, termite activity was monitored by using 808 Sentricon stations. Between January 2004 and July 2005, termites were found in 8-11 stations. In August 2005, the Park was flooded by Hurricane Katrina, but termites remained active. Post-Katrina termite activity levels of 16 21 stations were recorded throughout 2006, and in October 2007, the activity drastically increased to 43 stations. This rapid increase of termite activity continued into 2008, and a total of 94 stations harbored termite activities by July 2008. Termite activity peaked at 109 stations in September 2008 and then leveled down to 64 stations in March 2009. Termite activity in the Park between 2004 and 2009 was described by a Sigmoid model with a carrying capacity of 76 stations, and a Sigmoid mid-point of 1,202 d. In April 2009, a total of 14 colonies of Coptotermes formosanus Shiraki and one colony of Reticulitermes flavipes (Kollar) were delineated by using microsatellite genotyping and mark recapture protocol. Of the 15 colonies, eight near the Park border probably originated from existing colonies from outside, and seven C. formosanus colonies found inside the Park were probably initiated by alate pairs. Our results showed that, if surrounded by high population pressure of termites and no control measures are applied, an area cleared of termite populations by baits can be completely re-populated by termites from outside in 53 mo. PMID- 26896536 TI - Degradation of Insecticides in Poultry Manure: Determining the Insecticidal Treatment Interval for Managing House Fly (Diptera: Muscidae) Populations in Poultry Farms. AB - It is crucial to understand the degradation pattern of insecticides when designing a sustainable control program for the house fly, Musca domestica (L.), on poultry farms. The aim of this study was to determine the half-life and degradation rates of cyromazine, chlorpyrifos, and cypermethrin by spiking these insecticides into poultry manure, and then quantitatively analyzing the insecticide residue using ultra-performance liquid chromatography. The insecticides were later tested in the field in order to study the appropriate insecticidal treatment intervals. Bio-assays on manure samples were later tested at 3, 7, 10, and 15 d for bio-efficacy on susceptible house fly larvae. Degradation analysis demonstrated that cyromazine has the shortest half-life (3.01 d) compared with chlorpyrifos (4.36 d) and cypermethrin (3.75 d). Cyromazine also had a significantly greater degradation rate compared with chlorpyrifos and cypermethrin. For the field insecticidal treatment interval study, 10 d was the interval that had been determined for cyromazine due to its significantly lower residue; for ChCy (a mixture of chlorpyrifos and cypermethrin), the suggested interval was 7 d. Future work should focus on the effects of insecticide metabolites on targeted pests and the poultry manure environment. PMID- 26896537 TI - Differences in the timing of cardio-respiratory development determine whether marine gastropod embryos survive or die in hypoxia. AB - Physiological plasticity of early developmental stages is a key way by which organisms can survive and adapt to environmental change. We investigated developmental plasticity of aspects of the cardio-respiratory physiology of encapsulated embryos of a marine gastropod, Littorina obtusata, surviving exposure to moderate hypoxia (PO2 =8 kPa) and compared the development of these survivors with that of individuals that died before hatching. Individuals surviving hypoxia exhibited a slower rate of development and altered ontogeny of cardio-respiratory structure and function compared with normoxic controls (PO2 >20 kPa). The onset and development of the larval and adult hearts were delayed in chronological time in hypoxia, but both organs appeared earlier in developmental time and cardiac activity rates were greater. The velum, a transient, 'larval' organ thought to play a role in gas exchange, was larger in hypoxia but developed more slowly (in chronological time), and velar cilia driven, rotational activity was lower. Despite these effects of hypoxia, 38% of individuals survived to hatching. Compared with those embryos that died during development, these surviving embryos had advanced expression of adult structures, i.e. a significantly earlier occurrence and greater activity of their adult heart and larger shells. In contrast, embryos that died retained larval cardio respiratory features (the velum and larval heart) for longer in chronological time. Surviving embryos came from eggs with significantly higher albumen provisioning than those that died, suggesting an energetic component for advanced development of adult traits. PMID- 26896538 TI - Low cost of pulmonary ventilation in American alligators (Alligator mississippiensis) stimulated with doxapram. AB - To determine the costs of pulmonary ventilation without imposing severe oxygen limitations or acidosis that normally accompany exposures to hypoxia or hypercapnia, we opted to pharmacologically stimulate ventilation with doxapram (5 and 10 mg kg(-1)) in alligators. Doxapram is used clinically to alleviate ventilatory depression in response to anaesthesia and acts primarily on the peripheral oxygen-sensitive chemoreceptors. Using this approach, we investigated the hypothesis that pulmonary ventilation is relatively modest in comparison to resting metabolic rate in crocodilians and equipped seven juvenile alligators with masks for concurrent determination of ventilation and oxygen uptake. Doxapram elicited a dose-dependent and up to fourfold rise in ventilation, primarily by increasing ventilatory frequency. The accompanying rise in oxygen uptake was very small; ventilation in resting animals constitutes no more than 5% of resting metabolic rate. The conclusion that pulmonary ventilation is energetically cheap is consistent with earlier studies on alligators where ventilation was stimulated by hypoxia or hypercapnia. PMID- 26896539 TI - CHHBP: a newly identified receptor of crustacean hyperglycemic hormone. AB - Crustacean hyperglycemic hormone (CHH) is a neurohormone found only in arthropods that plays a pivotal role in the regulation of hemolymph glucose levels, molting and stress responses. Although it was determined that a membrane guanylyl cyclase (GC) acts as the CHH receptor in the Y-organ during ecdysteroidogenesis, the identity of the CHH receptor in the hepatopancreas has not been established. In this study, we identified CHH binding protein (CHHBP), as a potential receptor by screening the annotated unigenes from the transcriptome of ITALIC! Eriocheir sinensis, after removal of the eyestalk. Analysis of the binding affinity between CHH and CHHBP provided direct evidence that CHH interacts with CHHBP in a specific binding mode. Subsequent analysis showed that CHHBP is expressed primarily in the hepatopancreas where it localizes to the cell membrane. In addition, real-time PCR analysis showed that ITALIC! CHHBPtranscript levels gradually increase in the hepatopancreas following eyestalk ablation. RNAi mediated suppression of ITALIC! CHHBPexpression resulted in decreased glucose levels. Furthermore, the reduction of blood glucose induced by ITALIC! CHHBPRNAi reached the same level as that observed in the eyestalk ablation group, suggesting that CHHBP is involved in glucose metabolism regulated by CHH. In addition, compared with the control group, injection of CHH was unable to rescue the decreased glucose levels in ITALIC! CHHBPRNAi crabs. CHH induced transport of 2-NBDG to the outside of cells, with indispensable assistance from CHHBP. Taken together, these findings suggest that CHHBP acts as one type of the primary signal processor of CHH-mediated regulation of cellular glucose metabolism. PMID- 26896541 TI - Sea urchins in a high-CO2 world: partitioned effects of body size, ocean warming and acidification on metabolic rate. AB - Body size and temperature are the major factors explaining metabolic rate, and the additional factor of pH is a major driver at the biochemical level. These three factors have frequently been found to interact, complicating the formulation of broad models predicting metabolic rates and hence ecological functioning. In this first study of the effects of warming and ocean acidification, and their potential interaction, on metabolic rate across a broad range in body size (two to three orders of magnitude difference in body mass), we addressed the impact of climate change on the sea urchin ITALIC! Heliocidaris erythrogrammain context with climate projections for southeast Australia, an ocean warming hotspot. Urchins were gradually introduced to two temperatures (18 and 23 degrees C) and two pH levels (7.5 and 8.0), at which they were maintained for 2 months. Identical experimental trials separated by several weeks validated the fact that a new physiological steady state had been reached, otherwise known as acclimation. The relationship between body size, temperature and acidification on the metabolic rate of ITALIC! H. erythrogrammawas strikingly stable. Both stressors caused increases in metabolic rate: 20% for temperature and 19% for pH. Combined effects were additive: a 44% increase in metabolism. Body size had a highly stable relationship with metabolic rate regardless of temperature or pH. None of these diverse drivers of metabolism interacted or modulated the effects of the others, highlighting the partitioned nature of how each influences metabolic rate, and the importance of achieving a full acclimation state. Despite these increases in energetic demand there was very limited capacity for compensatory modulating of feeding rate; food consumption increased only in the very smallest specimens, and only in response to temperature, and not pH. Our data show that warming, acidification and body size all substantially affect metabolism and are highly consistent and partitioned in their effects, and for ITALIC! H. erythrogramma, near-future climate change will incur a substantial energetic cost. PMID- 26896542 TI - Musculoskeletal modelling of the dragonfly mandible system as an aid to understanding the role of single muscles in an evolutionary context. AB - Insects show a great variety of mouthpart and muscle configurations; however, knowledge of their mouthpart kinematics and muscle activation patterns is fragmentary. Understanding the role of muscle groups during movement and comparing them between insect groups could yield insights into evolutionary patterns and functional constraints. Here, we developed a mathematical inverse dynamic model including distinct muscles for an insect head-mandible-muscle complex based on micro-computed tomography (uCT) data and bite force measurements. With the advent of uCT, it is now possible to obtain precise spatial information about muscle attachment areas and head capsule construction in insects. Our model shows a distinct activation pattern for certain fibre groups potentially related to a geometry-dependent optimization. Muscle activation patterns suggest that intramandibular muscles play a minor role in bite force generation, which is a potential reason for their loss in several lineages of higher insects. Our model is in agreement with previous studies investigating fast and slow muscle fibres and is able to resolve the spatio temporal activation patterns of these different muscle types in insects. The model used here has a high potential for large-scale comparative analyses on the role of different muscle setups and head capsule designs in the megadiverse insects in order to aid our understanding of insect head capsule and mouthpart evolution under mechanical constraints. PMID- 26896540 TI - Forces generated during stretch in the heart of the lobster Homarus americanus are anisotropic and are altered by neuromodulators. AB - Mechanical and neurophysiological anisotropies mediate three-dimensional responses of the heart of ITALIC! Homarus americanus Although hearts ITALIC! in vivoare loaded multi-axially by pressure, studies of invertebrate cardiac function typically use uniaxial tests. To generate whole-heart length-tension curves, stretch pyramids at constant lengthening and shortening rates were imposed uniaxially and biaxially along longitudinal and transverse axes of the beating whole heart. To determine whether neuropeptides that are known to modulate cardiac activity in ITALIC! H. americanusaffect the active or passive components of these length-tension curves, we also performed these tests in the presence of SGRNFLRFamide (SGRN) and GYSNRNYLRFamide (GYS). In uniaxial and biaxial tests, both passive and active forces increased with stretch along both measurement axes. The increase in passive forces was anisotropic, with greater increases along the longitudinal axis. Passive forces showed hysteresis and active forces were higher during lengthening than shortening phases of the stretch pyramid. Active forces at a given length were increased by both neuropeptides. To exert these effects, neuropeptides might have acted indirectly on the muscle via their effects on the cardiac ganglion, directly on the neuromuscular junction, or directly on the muscles. Because increases in response to stretch were also seen in stimulated motor nerve-muscle preparations, at least some of the effects of the peptides are likely peripheral. Taken together, these findings suggest that flexibility in rhythmic cardiac contractions results from the amplified effects of neuropeptides interacting with the length-tension characteristics of the heart. PMID- 26896543 TI - Seasonal and sex differences in responsiveness to adrenocorticotropic hormone contribute to stress response plasticity in red-sided garter snakes (Thamnophis sirtalis parietalis). AB - As in many vertebrates, hormonal responses to stress vary seasonally in red-sided garter snakes (Thamnophis sirtalis parietalis). For example, males generally exhibit reduced glucocorticoid responses to a standard stressor during the spring mating season. We asked whether variation in adrenal sensitivity to adrenocorticotropic hormone (ACTH) explains why glucocorticoid responses to capture stress vary with sex, season and body condition in red-sided garter snakes. We measured glucocorticoids at 0, 1 and 4 h after injection with ACTH (0.1 IU g(-1)body mass) or vehicle in males and females during the spring mating season and autumn pre-hibernation period. Because elevated glucocorticoids can influence sex steroids, we also examined androgen and estradiol responses to ACTH. ACTH treatment increased glucocorticoids in both sexes and seasons. Spring collected males had a smaller integrated glucocorticoid response to ACTH than autumn-collected males. The integrated glucocorticoid response to ACTH differed with sex during the spring, with males having a smaller glucocorticoid response than females. Although integrated glucocorticoid responses to ACTH did not vary with body condition, we observed an interaction among season, sex and body condition. In males, ACTH treatment did not alter androgen levels in either season, but androgen levels decreased during the sampling period. Similar to previous studies, plasma estradiol was low or undetectable during the spring and autumn, and therefore any effect of ACTH treatment on estradiol could not be determined. These data provide support for a mechanism that partly explains how the hypothalamus-pituitary-adrenal (HPA) axis integrates information about season, sex and body condition: namely, variation in adrenal responsiveness to ACTH. PMID- 26896544 TI - High variability in stable isotope diet-tissue discrimination factors of two omnivorous freshwater fishes in controlled ex situ conditions. AB - Diet-tissue discrimination factors (Delta(13)C and Delta(15)N) are influenced by variables including the tissues being analysed and the taxon of the consumer and its prey. Whilst differences in Delta(13)C and Delta(15)N are apparent between herbivorous and piscivorous fishes, there is less known for omnivorous fishes that consume plant and animal material. Here, the omnivorous cyprinid fishes Barbus barbus and Squalius cephalus were held in tank aquaria and exposed to three diets that varied in their constituents (plant based to fishmeal based) and protein content (13% to 45%). After 100 days and isotopic replacement in fish tissues to 98%, samples of the food items, and dorsal muscle, fin tissue and scales were analysed for delta(13)C and delta(15)N. For both species and all diets, muscle was always enriched in delta(15)N and depleted in delta(13)C compared with fin tissue and scales. Across the different diets, Delta(13)C ranged between 2.00/00 and 5.60/00 and Delta(15)N ranged between 2.00/00 and 6.90/00. The diet based on plant material (20% protein) always resulted in the highest discrimination factors for each tissue, whilst the diet based on fishmeal (45% protein) consistently resulted in the lowest. The discrimination factors produced by non-fish diets were comparatively high compared with values in the literature, but were consistent with general patterns for some herbivorous fishes. These outputs suggest that the diet-tissue discrimination factors of omnivorous fishes will vary considerably between animal and plant prey, and these specific differences need consideration in predictions of their diet composition and trophic position. PMID- 26896545 TI - Mitochondrial physiology and reactive oxygen species production are altered by hypoxia acclimation in killifish (Fundulus heteroclitus). AB - Many fish encounter hypoxia in their native environment, but the role of mitochondrial physiology in hypoxia acclimation and hypoxia tolerance is poorly understood. We investigated the effects of hypoxia acclimation on mitochondrial respiration, O2kinetics, emission of reactive oxygen species (ROS), and antioxidant capacity in the estuarine killifish ( ITALIC! Fundulus heteroclitus). Killifish were acclimated to normoxia, constant hypoxia (5 kPa O2) or intermittent diel cycles of nocturnal hypoxia (12 h:12 h normoxia:hypoxia) for 28 33 days and mitochondria were isolated from liver. Neither pattern of hypoxia acclimation affected the respiratory capacities for oxidative phosphorylation or electron transport, leak respiration, coupling control or phosphorylation efficiency. Hypoxia acclimation also had no effect on mitochondrial O2kinetics, but ITALIC! P50(the O2tension at which hypoxia inhibits respiration by 50%) was lower in the leak state than during maximal respiration, and killifish mitochondria endured anoxia-reoxygenation without any impact on mitochondrial respiration. However, both patterns of hypoxia acclimation reduced the rate of ROS emission from mitochondria when compared at a common O2tension. Hypoxia acclimation also increased the levels of protein carbonyls and the activities of superoxide dismutase and catalase in liver tissue (the latter only occurred in constant hypoxia). Our results suggest that hypoxia acclimation is associated with changes in mitochondrial physiology that decrease ROS production and may help improve hypoxia tolerance. PMID- 26896546 TI - Comparison of the validity of Hill and Huxley muscle-tendon complex models using experimental data obtained from rat m. soleus in situ. AB - The relationship between mechanical and metabolic behaviour in the widely used Hill muscle-tendon complex (MTC) model is not straightforward, whereas this is an integral part of the Huxley model. In this study, we assessed to what extent Huxley- and Hill-type MTC models yield adequate predictions of mechanical muscle behaviour during stretch-shortening cycles (SSCs). In fully anaesthetized male Wistar rats (N=3), m. soleus was dissected completely free, except for the insertion. Cuff electrodes were placed over the n. ischiadicus. The distal end of the tendon was connected to a servo motor, via a force transducer. The setup allowed for full control over muscle stimulation and length, while force was measured. Quick-release and isovelocity contractions (part 1), and SSCs (part 2) were imposed. Simulations of part 2 were made with both a Hill and a Huxley MTC model, using parameter values determined from part 1. Modifications to the classic two-state Huxley model were made to incorporate series elasticity, activation dynamics, and active and passive force-length relationships. Results were similar for all rats. Fitting of the free parameters to the data of part 1 was near perfect (R(2)>0.97). During SSCs, predicted peak force and force during relaxation deviated from the experimental data for both models. Overall, both models yielded similarly adequate predictions of the experimental data. We conclude that Huxley and Hill MTC models are equally valid with respect to mechanical behaviour. PMID- 26896547 TI - Assessing acoustic communication active space in the Lusitanian toadfish. AB - The active space of a signal is an important concept in acoustic communication as it has implications for the function and evolution of acoustic signals. However, it remains mostly unknown for fish as it has been measured in only a restricted number of species. We combined physiological and sound propagation approaches to estimate the communication range of the Lusitanian toadfish's ( ITALIC! Halobatrachus didactylus) advertisement sound, the boatwhistle (BW). We recorded BWs at different distances from vocalizing fish in a natural nesting site at ca. 2-3 m depth. We measured the representation of these increasingly attenuated BWs in the auditory pathway through the auditory evoked potential (AEP) technique. These measurements point to a communication range of between 6 and 13 m, depending on the spectral characteristics of the BW. A similar communication range (ca. 8 m) was derived from comparing sound attenuation at selected frequencies with auditory sensitivity. This is one of the few studies to combine auditory measurements with sound propagation to estimate the active space of acoustic signals in fish. We emphasize the need in future studies for estimates of active space to take informational masking into account. PMID- 26896548 TI - Dynamic changes in scope for heart rate and cardiac autonomic control during warm acclimation in rainbow trout. AB - Time course studies are critical for understanding regulatory mechanisms and temporal constraints in ectothermic animals acclimating to warmer temperatures. Therefore, we investigated the dynamics of heart rate and its neuro-humoral control in rainbow trout ( ITALIC! Onchorhynchus mykissL.) acclimating to 16 degrees C for 39 days after being acutely warmed from 9 degrees C. Resting heart rate was 39 beats min(-1)at 9 degrees C, and increased significantly when fish were acutely warmed to 16 degrees C ( ITALIC! Q10=1.9), but then declined during acclimation ( ITALIC! Q10=1.2 at day 39), mainly due to increased cholinergic inhibition while the intrinsic heart rate and adrenergic tone were little affected. Maximum heart rate also increased with warming, although a partial modest decrease occurred during the acclimation period. Consequently, heart rate scope exhibited a complex pattern with an initial increase with acute warming, followed by a steep decline and then a subsequent increase, which was primarily explained by cholinergic inhibition of resting heart rate. PMID- 26896550 TI - Effect of body mass and melanism on heat balance in Liolaemus lizards of the goetschi clade. AB - The body temperature of ectotherms depends on the environmental temperatures and behavioral adjustments, but morphology may also have an effect. For example, in colder environments, animals tend to be larger and to show higher thermal inertia, as proposed by Bergmann's rule and the heat balance hypothesis (HBH). Additionally, dark coloration increases solar radiation absorption and should accelerate heat gain (thermal melanism hypothesis, TMH). We tested Bergmann's rule, the HBH and the TMH within the ITALIC! Liolaemus goetschilizard clade, which shows variability in body size and melanic coloration. We measured heating and cooling rates of live and euthanized animals, and tested how morphology and color affect these rates. Live organisms show less variable and faster heating rates compared with cooling rates, suggesting behavioral and/or physiological adjustments. Our results support Bergmann's rule and the HBH, as larger species show slower heating and cooling rates. However, we did not find a clear pattern to support the TMH. The influence of dorsal melanism on heating by radiation was masked by the body size effect in live animals, and results from euthanized individuals also showed no clear effects of melanism on heating rates. Comparison among three groups of live individuals with different degrees of melanism did not clarify the influence of melanism on heating rates. However, when euthanized animals from the same three groups were compared, we observed that darker euthanized animals actually heat faster than lighter ones, favoring the TMH. Although unresolved aspects remain, body size and coloration influenced heat exchange, suggesting complex thermoregulatory strategies in these lizards, probably regulated through physiology and behavior, which may allow these small lizards to inhabit harsh weather environments. PMID- 26896549 TI - Development of endothermy and concomitant increases in cardiac and skeletal muscle mitochondrial respiration in the precocial Pekin duck (Anas platyrhynchos domestica). AB - Attaining endothermic homeothermy occurs at different times post-hatching in birds and is associated with maturation of metabolic and aerobic capacity. Simultaneous measurements at the organism, organ and cellular levels during the transition to endothermy reveal means by which this change in phenotype occurs. We examined development of endothermy in precocial Pekin ducks ( ITALIC! Anas platyrhynchos domestica) by measuring whole-animal O2consumption ( ITALIC! VO2 ) as animals cooled from 35 to 15 degrees C. We measured heart ventricle mass, an indicator of O2delivery capacity, and mitochondrial respiration in permeabilized skeletal and cardiac muscle to elucidate associated changes in mitochondrial capacities at the cellular level. We examined animals on day 24 of incubation through 7 days post-hatching. ITALIC! VO2 of embryos decreased when cooling from 35 to 15 degrees C; ITALIC! VO2 of hatchlings, beginning on day 0 post-hatching, increased during cooling with a lower critical temperature of 32 degrees C. Yolk free body mass did not change between internal pipping and hatching, but the heart and thigh skeletal muscle grew at faster rates than the rest of the body as the animals transitioned from an externally pipped paranate to a hatchling. Large changes in oxidative phosphorylation capacity occurred during ontogeny in both thigh muscles, the primary site of shivering, and cardiac ventricles. Thus, increased metabolic capacity necessary to attain endothermy was associated with augmented metabolic capacity of the tissue and augmented increasing O2delivery capacity, both of which were attained rapidly at hatching. PMID- 26896551 TI - Stress, nutrition and parental care in a teleost fish: exploring mechanisms with supplemental feeding and cortisol manipulation. AB - Parental care is an essential life-history component of reproduction for many animal species, and it entails a suite of behavioural and physiological investments to enhance offspring survival. These investments can incur costs to the parent, reducing their energetic and physiological condition, future reproductive capabilities and survival. In fishes, relatively few studies have focused on how these physiological costs are mediated. Male smallmouth bass provide parental care for developing offspring until the brood reaches independence. During this energetically demanding life stage, males cease active foraging as they vigorously defend their offspring. Experimental manipulation of cortisol levels (via implantation) and food (via supplemental feeding) in parental males was used to investigate the fitness consequences of parental care. Improving the nutritional condition of nest-guarding males increased their reproductive success by reducing premature nest abandonment. However, supplemental feeding and cortisol treatment had no effect on parental care behaviours. Cortisol treatment reduced plasma lymphocyte numbers, but increased neutrophil and monocyte concentrations, indicating a shift in immune function. Supplemental feeding improved the physiological condition of parental fish by reducing the accumulation of oxidative injury. Specifically, supplemental feeding reduced the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) on DNA nucleotides. Increasing the nutritional condition of parental fish can reduce the physiological cost associated with intensive parental activity and improve overall reproductive success, illustrating the importance of nutritional condition as a key modulator of parental fitness. PMID- 26896556 TI - Reciprocal Negative Regulation between EGFR and DEPTOR Plays an Important Role in the Progression of Lung Adenocarcinoma. AB - The epidermal growth factor receptor (EGFR) activates downstream mTOR phosphorylation to promote the progression of many different tumor types, thus making it a prime therapeutic target. However, the role of DEP domain-containing mTOR-interacting protein (DEPTOR), a natural mTOR inhibitor, remains unclear in this process. Here, it is reported that EGFR expression is significantly increased in tumors of lung adenocarcinoma patients and is negatively correlated with the expression of DEPTOR. Activation of EGFR signaling, by EGF, in A549 lung adenocarcinoma cells (overexpressing EGFR) significantly enhanced the function of the mTOR autoamplification loop, consisting of S6K, mTOR, CK1alpha, and betaTrCP1, which resulted in downregulation of DEPTOR expression. Gefitinib, a specific EGFR inhibitor, stimulated DEPTOR accumulation by downregulating the function of the mTOR autoamplification loop. Furthermore, a series of assays conducted in DEPTOR knockout or ectopic expression in A549 cells confirmed that DEPTOR inhibited proliferation, migration, and invasion as well as the in vivo tumor growth of lung adenocarcinoma. Importantly, tumor progression mediated by EGFR ectopic expression was diminished by transfection with DEPTOR. This study uncovers the important inhibitory role of DEPTOR in lung adenocarcinoma progression and reveals a novel mechanism that EGFR downregulates DEPTOR expression to facilitate tumor growth. IMPLICATIONS: DEPTOR acts as a tumor suppressor by limiting EGFR-driven lung adenocarcinoma progression. Mol Cancer Res; 14(5); 448-57. (c)2016 AACR. PMID- 26896557 TI - Dexamethasone Intravitreal Implant for Diabetic Macular Edema During Pregnancy. AB - PURPOSE: To describe the management of diabetic macular edema during pregnancy with the use of a dexamethasone slow-release intravitreal implant. DESIGN: Retrospective, observational, consecutive case series. METHODS: The study included 5 pregnant women who presented with diabetic macular edema during pregnancy in the period from 2011 to 2014. Review of charts and photographs comprised best-corrected visual acuity (BCVA), foveal center field thickness assessed by optical coherence tomography, blood pressure, glycated hemoglobin, medications, and changes in such parameters after implant injection. RESULTS: Diabetic macular edema involving the foveal center was observed between gestational weeks 9 and 23 in 10 eyes of 5 patients. Dexamethasone intravitreal implant injection was given 10 times in 9 eyes with a mean preinjection center field retinal thickness of 535 MUm (range, 239-727 MUm) and a mean preinjection best-corrected visual acuity (BCVA) of 63 approximated Early Treatment Diabetic Retinopathy Study (approxETDRS) letters (range, 50-77 letters). One eye was unavailable for follow-up. In 7 of 8 eyes injection was followed, within 3 weeks, by a greater than 145 MUm reduction in foveal center field thickness and in 6 of 8 eyes by an increase in BCVA of 5 or more approxETDRS letters. A mild transient rise in intraocular pressure occurred in 3 out of 8 eyes. CONCLUSION: Diabetic macular edema involving the foveal center that presented during pregnancy responded promptly to intravitreal dexamethasone therapy by foveal thickness reduction and visual acuity improvement without clinically significant intraocular pressure increases. PMID- 26896559 TI - Quadrupedal movement training improves markers of cognition and joint repositioning. AB - INTRODUCTION: Exercise, and in particular balance and coordination related activities such as dance, appear to have positive effects on cognitive function, as well as neurodegenerative conditions such as dementia and Parkinson's disease. Quadrupedal gait training is a movement system requiring coordination of all four limbs that has previously been associated with cognitive development in children. There is currently little research into the effect of complex QDP movements on cognitive function in adults. PURPOSE: To determine the effects of a novel four week quadrupedal gait training programme on markers of cognitive function and joint reposition sense in healthy adults. METHODS: Twenty-two physically active sports science students (15 male and 7 female) were divided into two groups: a training group (TG) and a control group (CG). All participants completed the Wisconsin Card Sorting Task (WCST) and were tested for joint reposition sense before and after a four-week intervention, during which time the TG completed a series of progressive and challenging quadrupedal movement training sessions. RESULTS: Participants in the TG showed significant improvements in the WCST, with improvements in perseverative errors, non-perseverative errors, and conceptual level response. This improvement was not found in the CG. Joint reposition sense also improved for the TG, but only at 20degrees of shoulder flexion. CONCLUSIONS: Performance of a novel, progressive, and challenging task, requiring the coordination of all 4 limbs, has a beneficial impact on cognitive flexibility, and in joint reposition sense, although only at the specific joint angle directly targeted by the training. The findings are consistent with other studies showing improvements in executive function and joint reposition sense following physical activity. PMID- 26896558 TI - Regulators of mitochondrial dynamics in cancer. AB - Mitochondrial dynamics encompasses processes associated with mitochondrial fission and fusion, affecting their number, degree of biogenesis, and the induction of mitophagy. These activities determine the balance between mitochondrial energy production and cell death programs. Processes governing mitochondrial dynamics are tightly controlled in physiological conditions and are often deregulated in cancer. Mitochondrial protein homeostasis, transcriptional regulation, and post-translational modification are among processes that govern the control of mitochondrial dynamics. Cancer cells alter mitochondrial dynamics to resist apoptosis and adjust their bioenergetic and biosynthetic needs to support tumor initiating and transformation properties including proliferation, migration, and therapeutic resistance. This review focuses on key regulators of mitochondrial dynamics and their role in cancer. PMID- 26896561 TI - Normative perceptions of alcohol-related consequences among college students. AB - College students in the U.S. continue to drink in hazardous ways and experience a range of alcohol-related consequences. Personalized feedback interventions (PFIs), which often include normative components comparing personal drinking to that of similar peers, have been effective in reducing alcohol outcomes among college students. Though normative perceptions of the quantity and frequency of alcohol use have been examined in many studies, norms for alcohol-related consequences have received less attention. The current study examined self-other discrepancies (SODs) for alcohol-related consequences among college students. Participants overestimated how often alcohol-related consequences are experienced by other same-sex students on campus and rated consequences as more acceptable for others to experience than themselves. No differences in SODs were found between those who did and did not report alcohol use. Future studies should examine the efficacy of PFIs that incorporate normative feedback on alcohol related consequences. PMID- 26896560 TI - Anxiety sensitivity in relation to quit day dropout among adult daily smokers recruited to participate in a self-guided cessation attempt. AB - Anxiety sensitivity (AS; fear of anxiety and internal sensations) has been implicated in a variety of aspects of smoking, including difficulties achieving and maintaining abstinence during tobacco cessation. However, research has yet to evaluate whether AS impacts premature termination of initiating a quit attempt. Therefore, the aim of the present investigation was to explore the extent to which AS was associated with tobacco cessation dropout, as indexed by attendance on the scheduled quit day visit. Participants included 84 adult daily cigarette smokers (61.7% male; Mage=34.6years, SD=13.9), who were recruited to participate in a self-guided quit attempt (an attempt to quit smoking without professional or pharmacological aid). Results indicated that after controlling for the effects of participant sex, race, current (past month) psychological disorder, cigarettes smoked per day, number of years as a regular smoker, and pre-quit levels of motivation to quit, AS significantly predicted increased odds of study dropout prior to attending the scheduled quit day. These findings suggest that AS may be a mechanism involved with challenges in the initiation of quitting. PMID- 26896562 TI - New frontiers for anti-biofilm drug development. AB - Pathogenic microbial biofilm, a consortium of microbial cells protected by a self produced polymer matrix, is considered a worldwide challenge due to the inherent antibiotic resistance conferred by its lifestyle. Living, as it does, in a community of microbial organisms in a clinical situation, makes it responsible for severe and dangerous cases of infection. Combating this organisation of cells usually requires high antibiotic doses for a prolonged time, and these approaches often fail, contributing to infection persistence. In addition to therapeutic limitations, biofilms can be a source of infections when they grow in medical devices. The challenge imposed by biofilms has mobilised researchers in the entire world to prospect or develop alternatives to control biofilms. In this context, this review summarises the new frontiers that could be used in clinical circumstances in order to prevent or eliminate pathogenic biofilms. PMID- 26896563 TI - The diverse biological properties of the chemically inert noble gases. AB - The noble gases represent an intriguing scientific paradox. They are extremely inert chemically but display a remarkable spectrum of clinically useful biological properties. Despite a relative paucity of knowledge of their mechanisms of action, some of the noble gases have been used successfully in the clinic. Studies with xenon have suggested that the noble gases as a class may exhibit valuable biological properties such as anaesthesia; amelioration of ischemic damage; tissue protection prior to transplantation; analgesic properties; and a potentially wide range of other clinically useful effects. Xenon has been shown to be safe in humans, and has useful pharmacokinetic properties such as rapid onset, fast wash out etc. The main limitations in wider use are that: many of the fundamental biochemical studies are still lacking; the lighter noble gases are likely to manifest their properties only under hyperbaric conditions, impractical in surgery; and administration of xenon using convectional gaseous anaesthesia equipment is inefficient, making its use very expensive. There is nonetheless a significant body of published literature on the biochemical, pharmacological, and clinical properties of noble gases but no comprehensive reviews exist that summarize their properties and the existing knowledge of their models of action at the molecular (atomic) level. This review provides such an up-to-date summary of the extensive, useful biological properties of noble gases as drugs and prospects for wider application of these atoms. PMID- 26896564 TI - RF-amide neuropeptides and their receptors in Mammals: Pharmacological properties, drug development and main physiological functions. AB - RF-amide neuropeptides, with their typical Arg-Phe-NH2 signature at their carboxyl C-termini, belong to a lineage of peptides that spans almost the entire life tree. Throughout evolution, RF-amide peptides and their receptors preserved fundamental roles in reproduction and feeding, both in Vertebrates and Invertebrates. The scope of this review is to summarize the current knowledge on the RF-amide systems in Mammals from historical aspects to therapeutic opportunities. Taking advantage of the most recent findings in the field, special focus will be given on molecular and pharmacological properties of RF-amide peptides and their receptors as well as on their implication in the control of different physiological functions including feeding, reproduction and pain. Recent progress on the development of drugs that target RF-amide receptors will also be addressed. PMID- 26896566 TI - Recent advances in therapeutic strategies that focus on the regulation of ion channel expression. AB - A number of different ion channel types are involved in cell signaling networks, and homeostatic regulatory mechanisms contribute to the control of ion channel expression. Profiling of global gene expression using microarray technology has recently provided novel insights into the molecular mechanisms underlying the homeostatic and pathological control of ion channel expression. It has demonstrated that the dysregulation of ion channel expression is associated with the pathogenesis of neural, cardiovascular, and immune diseases as well as cancers. In addition to the transcriptional, translational, and post translational regulation of ion channels, potentially important evidence on the mechanisms controlling ion channel expression has recently been accumulated. The regulation of alternative pre-mRNA splicing is therefore a novel therapeutic strategy for the treatment of dominant-negative splicing disorders. Epigenetic modification plays a key role in various pathological conditions through the regulation of pluripotency genes. Inhibitors of pre-mRNA splicing and histone deacetyalase/methyltransferase have potential as potent therapeutic drugs for cancers and autoimmune and inflammatory diseases. Moreover, membrane-anchoring proteins, lysosomal and proteasomal degradation-related molecules, auxiliary subunits, and pharmacological agents alter the protein folding, membrane trafficking, and post-translational modifications of ion channels, and are linked to expression-defect channelopathies. In this review, we focused on recent insights into the transcriptional, spliceosomal, epigenetic, and proteasomal regulation of ion channel expression: Ca(2+) channels (TRPC/TRPV/TRPM/TRPA/Orai), K(+) channels (voltage-gated, KV/Ca(2+)-activated, KCa/two-pore domain, K2P/inward-rectifier, Kir), and Ca(2+)-activated Cl(-) channels (TMEM16A/TMEM16B). Furthermore, this review highlights expression of these ion channels in expression-defect channelopathies. PMID- 26896567 TI - Effect of Liuwei Dihuang decoction, a traditional Chinese medicinal prescription, on the neuroendocrine immunomodulation network. AB - Liuwei Dihuang decoction (LW) has been used in traditional Chinese medicine (TCM) for more than 900years to prevent and treat various diseases with characteristic features of kidney yin deficiency. To date, LW has been commonly prescribed in TCM as therapy or adjuvant therapy against various diseases. To elucidate the pharmacological characteristics and mechanism of action of this formula, studies have been conducted on the pharmacological effects and chemical profiles (including bioactive ingredients) to investigate the role of LW in the neuroendocrine immunomodulation (NIM) network. In this review, we provide an overview of the pharmacological effects of LW on the NIM network, particularly on learning and memory, immunomodulation, and neuroendocrine-immune interactions, including the effects of LW on the central nervous system, endocrine system, and immune system. We also discuss advances in related chemical studies, especially those identifying the bioactive components of LW and their unique combinational effects on the immune system. Our experimental results indicate that LW exerts a broad spectrum of pharmacological effects, by modulating and restoring the balance of the NIM network disturbed by several pathological factors. PMID- 26896568 TI - Expression of RYamide in the nervous and endocrine system of Bombyx mori. AB - RYamides are neuropeptides encoded by a gene whose precise expression and function have not yet been determined. We identified the RYamide gene transcript (fmgV1g15f, SilkBase database) and predicted two candidates for G-protein coupled RYamide receptors (A19-BAG68418 and A22-BAG68421) in the silkworm Bombyx mori. We cloned the RYamide transcript and described its spatial expression using in situ hybridisation. In the larval central nervous system (CNS) expression of RYamide was restricted to 12-14 small neurons in the brain and two posterior neurons in the terminal abdominal ganglion. During metamorphosis their number decreased to eight protocerebral neurons in the adults. Multiple staining, using various insect neuropeptide antibodies, revealed that neurons expressing RYamide are different from other peptidergic cells in the CNS. We also found RYamide expression in the enteroendocrine cells (EC) of the anterior midgut of larvae, pupae and adults. Two minor subpopulations of these EC were also immunoreactive to antibodies against tachykinin and myosupressin. This expression pattern suggests RYamides may play a role in the regulation of feeding and digestion. PMID- 26896565 TI - DNA repair targeted therapy: The past or future of cancer treatment? AB - The repair of DNA damage is a complex process that relies on particular pathways to remedy specific types of damage to DNA. The range of insults to DNA includes small, modest changes in structure including mismatched bases and simple methylation events to oxidized bases, intra- and interstrand DNA crosslinks, DNA double strand breaks and protein-DNA adducts. Pathways required for the repair of these lesions include mismatch repair, base excision repair, nucleotide excision repair, and the homology directed repair/Fanconi anemia pathway. Each of these pathways contributes to genetic stability, and mutations in genes encoding proteins involved in these pathways have been demonstrated to promote genetic instability and cancer. In fact, it has been suggested that all cancers display defects in DNA repair. It has also been demonstrated that the ability of cancer cells to repair therapeutically induced DNA damage impacts therapeutic efficacy. This has led to targeting DNA repair pathways and proteins to develop anti-cancer agents that will increase sensitivity to traditional chemotherapeutics. While initial studies languished and were plagued by a lack of specificity and a defined mechanism of action, more recent approaches to exploit synthetic lethal interaction and develop high affinity chemical inhibitors have proven considerably more effective. In this review we will highlight recent advances and discuss previous failures in targeting DNA repair to pave the way for future DNA repair targeted agents and their use in cancer therapy. PMID- 26896570 TI - Integrated Loss of miR-1/miR-101/miR-204 Discriminates Metastatic from Nonmetastatic Penile Carcinomas and Can Predict Patient Outcome. AB - PURPOSE: Penile squamous cell carcinoma is a rare but aggressive cancer. Little is known about pivotal events in tumor pathogenesis and metastasis. Lymph node metastasis is the prevailing prognostic factor while clinical detection in patients remains difficult. Our aim was to identify distinct miRNAs that are differentially expressed in metastatic vs nonmetastatic penile carcinoma, which may serve as diagnostic biomarkers for disease progression. MATERIALS AND METHODS: TaqMan(r) arrays and quantitative polymerase chain reaction were applied to analyze miRNA profiles in penile squamous cell carcinoma specimens and glans tissue from 24 patients. The prognostic value of deregulated miRNAs was analyzed using the Kaplan-Meier method. The Spearman test was applied to determine a potential linkage between distinctive miRNAs in individual patients. RESULTS: Loss of miR-1 (p = 0.0048), miR-101 (p = 0.0001) and miR-204 (p = 0.0004) in metastasizing tumors and associated metastases (p = 0.0151, 0.0019 and 0.0003, respectively) distinguished patients with metastatic and nonmetastatic penile squamous cell carcinoma. These 3 miRNAs showed a coherent expression pattern. Consistently, patients with low levels of all 3 miRNAs had worse survival (p = 0.03). We identified a coordinately regulated miRNA target hub that is over expressed in penile squamous cell carcinoma and associated with lymphovascular invasion. CONCLUSIONS: Our results provide evidence of a novel multiple miRNA based signature associated with lymph node metastasis and unfavorable prognosis of penile squamous cell carcinoma. The integrated loss of miR-1, miR-101 and miR 204 may predict the formation of metastases in penile cancer at an early stage. PMID- 26896571 TI - A validated simultaneous quantification method for vonoprazan (TAK-438F) and its 4 metabolites in human plasma by the liquid chromatography-tandem mass spectrometry. AB - Vonoprazan fumarate (TAK-438) is a potassium-competitive acid blocker which was approved in Japan for a treatment of acid-related diseases. In this study a simple and validated bioanalytical method, which can simultaneously determine vonoprazan (TAK-438F) and its four metabolites (M-I, M-II, M-III and M-IV-Sul) in human plasma, was developed. The method is based on protein precipitation and subsequent ultra-high performance liquid chromatography separation followed by tandem mass spectrometry detection. The mass spectrometric parameters for detection of TAK-438F, M-I, M-III and M-IV-Sul were modified from their optimum values in order to achieve a simultaneous quantification while retaining enough sensitivity and wide dynamic ranges for all the target analytes. The validity and robustness of the method was verified through a validation study as per the regulatory guidance on bioanalytical method validation. The calibration ranges are 0.1-100 ng/mL for TAK-438F and M-III, and 1-1000 ng/mL for M-I, M-II and M-IV Sul using the 100 MUL of human plasma. The total run time per sample is 5 min. The working solution for M-III was recommended to be prepared separately, especially for the long-term use, in order to avoid the instability of M-III in the mixed working solutions, which could cause the high consumption of reference standards. The established method was applied to clinical pharmacokinetic studies and concentrations of all the analytes in human plasma were successfully determined with high reproducibility ensured by incurred sample reanalysis, indicating the suitableness of the established method. PMID- 26896569 TI - The corticotropin-releasing factor-like diuretic hormone 44 (DH44) and kinin neuropeptides modulate desiccation and starvation tolerance in Drosophila melanogaster. AB - Malpighian tubules are critical organs for epithelial fluid transport and stress tolerance in insects, and are under neuroendocrine control by multiple neuropeptides secreted by identified neurons. Here, we demonstrate roles for CRF like diuretic hormone 44 (DH44) and Drosophila melanogaster kinin (Drome-kinin, DK) in desiccation and starvation tolerance. Gene expression and labelled DH44 ligand binding data, as well as highly selective knockdowns and/or neuronal ablations of DH44 in neurons of the pars intercerebralis and DH44 receptor (DH44 R2) in Malpighian tubule principal cells, indicate that suppression of DH44 signalling improves desiccation tolerance of the intact fly. Drome-kinin receptor, encoded by the leucokinin receptor gene, LKR, is expressed in DH44 neurons as well as in stellate cells of the Malpighian tubules. LKR knockdown in DH44-expressing neurons reduces Malpighian tubule-specific LKR, suggesting interactions between DH44 and LK signalling pathways. Finally, although a role for DK in desiccation tolerance was not defined, we demonstrate a novel role for Malpighian tubule cell-specific LKR in starvation tolerance. Starvation increases gene expression of epithelial LKR. Also, Malpighian tubule stellate cell-specific knockdown of LKR significantly reduced starvation tolerance, demonstrating a role for neuropeptide signalling during starvation stress. PMID- 26896572 TI - Metabolomics approach to explore the effects of Kai-Xin-San on Alzheimer's disease using UPLC/ESI-Q-TOF mass spectrometry. AB - Alzheimer's disease (AD) is a multifactorial neurodegenerative disease that influences elderly populations, with no effective method for its treatment so far. To improve its diagnosis and treatment, changes of small molecule metabolite during AD should be elucidated. Kai-Xin-San (KXS) is an herbal formulae that has been widely used to treat mental disorders, especially amnesia and depression in China. Experimental AD was induced in rats by an intraperitoneal injection of d galactose (d-gal) and administered intragastrically with aluminum chloride (AlCl3) simultaneously for 105 days. Morris water maze task as a behavior test was used for testing the effects of KXS on AD model and pathological changes to the brain were assessed by hematoxylin-eosin staining and immunohistochemistry. The levels of Bcl-2 and ChAT in hippocampus were evaluated by western-blot. Furthermore, metabolite profiling of AD was performed through ultra-performance liquid chromatography/electrospray ionization quadruple time-of- flight-high definition mass spectrometry (UPLC/ESI-Q-TOF/HDMS) combined with pattern recognition approaches and pathway analysis. d-gal and AlCl3-treated caused a decline in spatial learning and memory, hippocampal histopathological abnormalities and increased Abeta1-40 levels in the brain cortex and hippocampus along with decreased Bcl-2 and ChAT expression in the hippocampus. KXS significantly improved the cognitive impairment induced by d-gal and AlCl3, attenuated hippocampal histopathological abnormalities, reduced Abeta1-40 levels and increased Bcl-2 and ChAT expression in the hippocampus. A total of 48 metabolites were considered as potential biomarkers of AD, and 36 metabolites may correlate with the regulation of KXS treatment on AD. Changes in AD metabolic profiling were close to normal states through regulating multiple perturbed pathways after KXS treatment. This study has revealed the potential biomarkers and metabolic networks of AD, illuminated the biochemistry mechanism of AD and the metabolic pathways influenced by KXS. PMID- 26896574 TI - Understanding the neurobiology of MMN and its reduction in schizophrenia. PMID- 26896573 TI - Determination of American ginseng saponins and their metabolites in human plasma, urine and feces samples by liquid chromatography coupled with quadrupole time-of flight mass spectrometry. AB - American ginseng is a commonly consumed herbal medicine in the United States and other countries. Ginseng saponins are considered to be its active constituents. We have previously demonstrated in an in vitro experiment that human enteric microbiota metabolize ginseng parent compounds into their metabolites. In this study, we analyzed American ginseng saponins and their metabolites in human plasma, urine and feces samples by liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS). Six healthy male volunteers ingested 1 g of American ginseng twice a day for 7 days. On day 7, biological samples were obtained and pretreated with solid phase extraction. The ginseng constituents and their metabolites were characterized, including 5 ginseng metabolites in plasma, 10 in urine, and 26 in feces. For the plasma, urine and feces samples, the levels of ginsenoside Rb1 (a major parent compound) were 8.6, 56.8 and 57.7 ng/mL, respectively, and the levels of compound K (a major metabolite) were 58.4 ng/mL, 109.8 ng/mL and 10.06 MUg/mL, respectively. It suggested that compound K had a remarkably high level in all three samples. Moreover, in human feces, ginsenoside Rk1 and Rg5, Rk3 and Rh4, Rg6 and F4 were detected as the products of dehydration. Further studies are needed to evaluate the pharmacological activities of the identified ginseng metabolites. PMID- 26896575 TI - Walk or ride? Phoretic behaviour of amblyceran and ischnoceran lice. AB - Phoresy is a behaviour where one organism hitches a ride on another more mobile organism. This is a common dispersal mechanism amongst relatively immobile species that specialise on patchy resources. Parasites specialise on patchily distributed resources: their hosts. Although host individuals are isolated in space and time, parasites must transmit between hosts or they will die with their hosts. Lice are permanent obligate ectoparasites that complete their entire life cycle on their host. They typically transmit when hosts come into direct contact; however, lice are also capable of transmitting phoretically. Yet, phoresy is rare amongst some groups of lice. Fundamental morphological differences have traditionally been used to explain the phoretic differences amongst different suborders of lice; however, these hypotheses do not fully explain observed patterns. We propose that a more fundamental natural history trait may better explain variation in phoresy. Species able to disperse under their own power should be less likely to engage in phoresy than more immobile species. Here we experimentally tested the relationship between independent louse mobility and phoresy using a system with four species of lice (Phthiraptera: Ischnocera and Amblycera) that all parasitize a single host species, the Rock Pigeon (Columba livia). We quantified the relative ability of all four species of lice to move independently off the host, and we quantified their ability to attach to, and remain attached to, hippoboscid flies (Pseudolynchia canariensis). Our results show that the most mobile louse species is the least phoretic, and the most phoretic species is quite immobile off the host. Our findings were consistent with the hypothesis that phoretic dispersal should be rare amongst species of lice that are capable of independent dispersal; however other factors such as interspecific competition may also play a role. PMID- 26896577 TI - Occurrence and profiling of multiple nitrosamines in source water and drinking water of China. AB - The occurrence of multiple nitrosamines was investigated in 54 drinking water treatment plants (DWTPs) from 30 cities across major watersheds of China, and the formation potential (FP) and cancer risk of the dominant nitrosamines were studied for profiling purposes. The results showed that N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA) and N-nitrosodi-n-butylamine (NDBA) were the most abundant in DWTPs, and the concentrations in source water and finished water samples were not detected (ND) -53.6ng/L (NDMA), ND -68.5ng/L (NDEA), ND 48.2ng/L (NDBA). The frequencies of detection in source waters were 64.8%, 61.1% and 51.8%, and 57.4%, 53.7%, and 37% for finished waters, respectively. Further study indicated that the FPs of the three main nitrosamines during chloramination were higher than those during chlorination and in drinking water. The results of Principal Components Analysis (PCA) showed that ammonia was the most closely associated factor in nitrosamine formation in the investigated source water; however, there was no significant correlation between nitrosamine-FPs and the values of dominant water-quality parameters. The advanced treatment units (i.e., ozonation and biological activated carbon) used in DWTPs were able to control the nitrosamine-FPs effectively after disinfection. The target pollutants posed median and maximum cancer risks of 2.99*10(-5) and 35.5*10(-5) to the local populations due to their occurrence in drinking water. PMID- 26896576 TI - Phenotypic and molecular analysis of the effect of 20-hydroxyecdysone on the human filarial parasite Brugia malayi. AB - A homologue of the ecdysone receptor has been identified and shown to be responsive to 20-hydroxyecdysone in Brugia malayi. However, the role of this master regulator of insect development has not been delineated in filarial nematodes. Gravid adult female B. malayi cultured in the presence of 20 hydroxyecdysone produced significantly more microfilariae and abortive immature progeny than control worms, implicating the ecdysone receptor in regulation of embryogenesis and microfilarial development. Transcriptome analyses identified 30 genes whose expression was significantly up-regulated in 20-hydroxyecdysone treated parasites compared with untreated controls. Of these, 18% were identified to be regulating transcription. A comparative proteomic analysis revealed 932 proteins to be present in greater amounts in extracts of 20-hydroxyecdysone treated adult females than in extracts prepared from worms cultured in the absence of the hormone. Of the proteins exhibiting a greater than two-fold difference in the 20-hydroxyecdysone-treated versus untreated parasite extracts, 16% were involved in transcriptional regulation. RNA interference (RNAi) phenotype analysis of Caenorhabditis elegans orthologs revealed that phenotypes involved in developmental processes associated with embryogenesis were significantly over-represented in the transcripts and proteins that were up regulated by exposure to 20-hydroxyecdysone. Taken together, the transcriptomic, proteomic and phenotypic data suggest that the filarial ecdysone receptor may play a role analogous to that in insects, where it serves as a regulator of egg development. PMID- 26896579 TI - Direct and indirect causes of sex differences in mercury concentrations and parasitic infections in a marine bird. AB - In many animal species, males and females differ in their levels of contaminants and/or parasitic infections. Most contaminants and gastro-intestinal parasites are obtained through prey ingestion, and thus the causes of sex differences in the distribution of these factors might follow similar pathways. We studied the northern common eider duck (Somateria molissima borealis) as an avian model, and used directed separation path analysis to explore the causes of sex differences in mercury (Hg) and gastro-intestinal helminths. Two trophically transmitted helminths were examined: a cestode (Lateriporus sp.) and an acanthocephalan (Polymorphus sp). We found that the number of Lateriporus sp. varied positively with stable isotope signature (as indicated by delta(15)N in eider breast muscle tissue), and negatively with crustaceans being present in the short term diet. We also found that Polymorphus sp. varied positively with eider tissue stable isotope signature. However, Polymorphus sp. varied negatively with sex indirectly through condition and liver mass. Similarly, Hg concentrations also varied negatively with sex indirectly through condition and liver mass, with both Polymorphus sp. intensity and Hg concentrations significantly higher in males. We found that model fit increased when a negative relationship between the two helminth species was included, suggesting a yet unknown causal mechanism linking these parasites. Our findings suggest that although Hg and gastro-intestinal parasites are both trophically transmitted through the eider's prey items, the factors that contribute towards bioaccumulation of these two burdens differ in source, likely caused by several different factors and may potentially influence each other. PMID- 26896578 TI - Small lakes in big landscape: Multi-scale drivers of littoral ecosystem in alpine lakes. AB - In low nutrient alpine lakes, the littoral zone is the most productive part of the ecosystem, and it is a biodiversity hotspot. It is not entirely clear how the scale and physical heterogeneity of surrounding catchment, its ecological composition, and larger landscape gradients work together to sustain littoral communities. A total of 113 alpine lakes from the central Pyrenees were surveyed to evaluate the functional connectivity between littoral zoobenthos and landscape physical and ecological elements at geographical, catchment and local scales, and to ascertain how they affect the formation of littoral communities. At each lake, the zoobenthic composition was assessed together with geolocation, catchment hydrodynamics, geomorphology and topography, riparian vegetation composition, the presence of trout and frogs, water pH and conductivity. Multidimensional fuzzy set models integrating benthic biota and environmental variables revealed that at geographical scale, longitude unexpectedly surpassed altitude and latitude in its effect on littoral ecosystem. This reflects a sharp transition between Atlantic and Mediterranean climates and suggests a potentially high horizontal vulnerability to climate change. Topography (controlling catchment type, snow coverage and lakes connectivity) was the most influential catchment-scale driver, followed by hydrodynamics (waterbody size, type and volume of inflow/outflow). Locally, riparian plant composition significantly related to littoral community structure, richness and diversity. These variables, directly and indirectly, create habitats for aquatic and terrestrial stages of invertebrates, and control nutrient and water cycles. Three benthic associations characterised distinct lakes. Vertebrate predation, water conductivity and pH had no major influence on littoral taxa. This work provides exhaustive information from relatively pristine sites, and unveils a strong connection between littoral ecosystem and catchment heterogeneity at scales beyond the local environment. This underpins the role of alpine lakes as sensors of local and large-scale environmental changes, which can be used in monitoring networks to evaluate further impacts. PMID- 26896580 TI - Effects of invasive fish and quality of water and sediment on macrophytes biomass, and their consequences for the waterbird community of a Mediterranean floodplain. AB - Floodplains are among the most threatened ecosystems world-wide because of multiple stressors, i.e., invasive species, pollution and aquifer overexploitation; the Tablas de Daimiel National Park (Spain) is a clear example of these kinds of impact. This work aims to test whether invasive fish and/or the water and sediment quality are significant drivers of the decline of stonewort (Chara spp.) meadows in the Tablas de Daimiel, investigating how this could explain changes observed in the waterbird community. Bird surveys performed monthly between June 2010 and April 2014 have shown that herbivorous species like the red-crested pochard (Netta rufina) reached historical records between September 2010 and June 2011, but have decreased since then. Piscivorous waterbirds like the great cormorant (Phalacrocorax carbo) and herons increased in population after 2011, however. These changes may be due to the decline of Chara spp. meadows, connected to overexploitation by herbivores, or to changes in water and sediment quality. To test this hypothesis, we studied the growth of Chara spp. biomass in ten sites of the Tablas de Daimiel, where experimental exclosures were set up to exclude herbivory by birds, and bioturbation and herbivory by fish. Our results have shown that the absence of Chara spp. in the Tablas de Daimiel is mostly explained by presence of invasive fish (i.e. common carp). Moreover, the physicochemical characteristics of the water (lower values of conductivity and higher values of inorganic carbon and organic nitrogen), as well as of the sediment (lower values of inorganic and organic phosphorus), favour the increase of Chara spp., in the absence of the fish effect. These results led the National Park managers to begin the control of invasive fish as an urgent measure to assure the ecological conservation of this Mediterranean wetland. PMID- 26896581 TI - Impact of tillage erosion on water erosion in a hilly landscape. AB - Little has been known of the interaction between tillage erosion and water erosion, while the two erosion processes was independently studied. Can tillage induced soil redistribution lead to exaggerated (or retarded) runoff flow and sediment concentrations in steeply sloping fields? A series of simulated tillage and artificial rainfall events were applied to rectangular runoff plots (2m*8m) with a slope of 15 degrees to examine the impacts of tillage erosion intensities on water erosion in the Yangtze Three Gorges Reservoir Area, China. Mean flow velocity, effective/critical shear stress, and soil erodibility factor K were calculated to analyze the differences in hydrodynamic characteristics induced by tillage. Our experimental results suggest that mean runoff rates were 2.26, 1.19, and 0.65Lmin(-1) and that mean soil detachment rates were 1.53, 1.01, and 0.61gm( 2)min(-1) during the 70-min simulated rainfall events for 52-, 31-, and 10-year tillage, respectively. A significant difference (P<0.05) in cumulative detachment amounts was found among different tillage intensities. Compared with the soil flux of 0kgm(-1), cumulative detachment amounts for the soil fluxes of 9.86 and 24.72kgm(-1) increased by 40.02% and 100.94%, respectively, during the 30-min rainfall event. The results imply that soil and water losses tended to increase with increasing tillage intensity. A significant difference in mean flow velocity occurred near the upper and lower slope boundaries of the field, while significant differences (P<0.05) in runoff depth and effective shear stress were observed among different slope positions. Soil erodibility factor K for the soil fluxes of 9.86 and 24.72kgm(-1) were 2.40 and 5.11 times higher, respectively, than that for the soil flux of 0kgm(-1). As tillage intensity increased, critical shear stress trended to gradually decrease for all soil fluxes. Our results indicate that tillage erosion increases soil erodibility and delivers the soil for water erosion in sloping fields, accelerating water erosion. PMID- 26896583 TI - A new approach to the assessment of flooding and dampness hazards in cultural heritage, applied to the historic centre of Seville (Spain). AB - Flooding and dampness have caused considerable damage to historic towns and cities and have become more frequent in recent years. The aim of this paper is to analyse the hazards of flooding and dampness in historic cities to establish a methodology that prioritises preventive conservation actions and restorations. The case study concerns the historic centre of Seville (Spain) and parish churches built between the 13th and 18th centuries. Geographic information system (GIS) software has been used to assess hazards caused by flooding and dampness along with a Delphi consultation process surveying a multidisciplinary group of seven experts-archaeologists, geologists, chemists, architects, engineers and environmentalists-to gain a general overview of the hazards affecting each area of the city. Currently, the historic centre of Seville is at a very low risk of flooding due to the engineering works being undertaken to divert the river course. For flooding to occur, water levels would need to rise over 6 to 12m along the different sections of the defensive walls; as a result, the historic centre has not been flooded since 1961, when these defences broke. However, there is a continual presence of dampness due to the proximity of the river, the presence of underground water and the permeability of the subsoil, resulting in continual damage to the lower sections of the monuments studied. Hence, hazard maps of flooding and dampness need to be dovetailed. This new approach provides tools for decision-makers in the current crisis, allowing them to prioritise strategies that will minimise damage in a town, as the urban unit where territorial policies could be applied. PMID- 26896582 TI - Temporal characterization and regional contribution to O3 and NOx at an urban and a suburban site in Nanjing, China. AB - To improve our understanding of the interplay among local and regional photochemical pollutants in the typical city of the Yangtze River Delta (YRD) region, the concurrent observation of O3 and NOx concentrations at an urban and a suburban site in Nanjing during 2008 is presented. In general, the annual mean O3 concentration is 2.35ppbv lower in the downtown than at suburban due to higher NOx pollution levels correlated with heavy traffic. At both sites, O3 shows a distinct seasonality with the spring maximum and the winter minimum, while the minimum concentration of NOx appears in summertime. Besides the chemical processes of O3 sensitivity in the daytime and the NOx titration at night, meteorological conditions also play an essential role in these monthly and diurnal variations. The ozone weekend effect that can be attributed to the weekly routine of human activities is observed in the urban atmosphere of Nanjing as well, with O3 concentrations 2.09ppbv higher and NOx concentrations 6.20ppbv lower on weekends than on weekdays. The chemical coupling of NO, NO2 and O3 is investigated to show that the OX-component (O3 and NO2) partitioning point occurs at about 35ppbv for NOx, with O3 being the dominant form at lower levels and NO2 dominating at higher levels. And it is also discovered that the level of OX is made up of two contributions, including the regional contribution affected by regional background O3 level and the local contribution correlated with the level of primary pollution. The diurnal peak of regional contribution appears 2-5h after the peak of local contribution, implying that OX in Nanjing might prominently affected by the pollutants from a short distance. The highest regional contribution and the second highest local contribution lead to the spring peak of O3 observed in Nanjing, whereas the highest local contribution and the moderate regional contribution make the O3 concentrations in summer higher than those in autumn and winter. Our results reveal the important environment impacts from meteorological conditions and human activities in the YRD region, and can help to understand O3 pollution in these polluted areas by just using the conventional observations. PMID- 26896584 TI - Negative effects of excessive soil phosphorus on floristic quality in Ohio wetlands. AB - Excessive soil nutrients, often from agricultural runoff, have been shown to negatively impact some aspects of wetland plant communities. We measured plant available phosphorus (Mehlich-3: MeP) in soil samples, and assessed the vascular plant community and habitat degradation at 27 emergent and 13 forested wetlands in Ohio, USA. We tested two hypotheses: (1) that an index of vegetation biological integrity based on floristic quality was lower in wetlands with higher concentrations of MeP in the soil, and (2) that higher concentrations of MeP occurred in wetlands with more habitat degradation (i.e., lower quality), as estimated by a rapid assessment method. Hypothesis (1) was supported for emergent, but not for forested wetlands. Hypothesis (2) was marginally supported (P=0.09) for emergent, but not supported for forested wetlands. The results indicate that the effect of concentration of phosphorus in wetland soils and the quality of plant species assemblages in wetlands is more complex than shown in site-specific studies and may depend in part on degree of disturbance in the surrounding watershed and dominant wetland vegetation type. Woody plants in forested wetlands are typically longer lived than herbaceous species in the understory and emergent wetlands, and may persist despite high inputs of phosphorus. Further, the forested wetlands were typically surrounded by a wide band of forest vegetation, which may provide a barrier against sedimentation and the associated phosphorus inputs to the wetland interior. Our results indicate that inferences about soil nutrient conditions made from rapid assessment methods for assessing wetland habitat condition may not be reliable. PMID- 26896585 TI - Integration of transport concepts for risk assessment of pesticide erosion. AB - Environmental contamination by agrochemicals has been a large problem for decades. Pesticides are transported in runoff and remain attached to eroded soil particles, posing a risk to water and soil quality and human health. We have developed a parsimonious integrative model of pesticide displacement by runoff and erosion that explicitly accounts for water infiltration, erosion, runoff, and pesticide transport and degradation in soil. The conceptual framework was based on broadly accepted assumptions such as the convection-dispersion equation and lognormal distributions of soil properties associated with transport, sorption, degradation, and erosion. To illustrate the concept, a few assumptions are made with regard to runoff in relatively flat agricultural fields: dispersion is ignored and erosion is modelled by a functional relationship. A sensitivity analysis indicated that the total mass of pesticide associated with soil eroded by water scouring increased with slope, rain intensity, and water field capacity of the soil. The mass of transported pesticide decreased as the micro-topography of the soil surface became more distinct. The timing of pesticide spraying and rate of degradation before erosion negatively affected the total amount of transported pesticide. The mechanisms involved in pesticide displacement, such as runoff, infiltration, soil erosion, and pesticide transport and decay in the topsoil, were all explicitly accounted for, so the mathematical complexity of their description can be high, depending on the situation. PMID- 26896586 TI - Removal and co-transport of Zn, As(V), and Cd during leachate seepage through downgradient mine soils: A batch sorption and column study. AB - The removal of Zn, As(V), and Cd during the leachate seepage process was measured in single, binary, and ternary solute systems by batch sorption and 1-D column flow experiments, followed by a sequential extraction procedure (SEP). In single solute systems, sorption (Kd(*)) occurred in the order of As(V)>Zn?Cd, and this sequence did not change in the presence of other solutes. In multi-solute systems, the sorption of Zn (~20%) and Cd (~27%) was enhanced by As(V), while Zn and Cd suppressed the sorption of each other. In all cases, As(V) sorption was not affected by the cations, indicating that As(V) is prioritized by sorption sites to a much greater degree than Zn and Cd. Element retention by column soils was strongly correlated (r(2)=0.77) with Kd(*). Across column segments, mass retention was in the order of inlet (36-54%)>middle (26-35%)>outlet (20-31%), except for Cd in the Zn-Cd binary system. The result of SEP revealed that most of the retained Cd (98-99%) and Zn (56-71%) was in the labile fraction (e.g., the sum of F1 and F2) while only 9-12% of As(V) was labile and most (>55%) was specifically adsorbed to Fe/Al oxides. Plots of the labile fraction (f(labile)) and the fast sorption fraction (f(fast)) suggested that the kinetics of specific As(V) sorption occur rapidly (f(fast)>f(labile)), whereas labile Zn and Cd sorption occurs slowly (f(labile)>f(fast)), indicating the occurrence of kinetically limited labile sorption sites, probably due to Zn-Cd competition. In conclusion, the element leaching potential of mine leachate can be greatly attenuated during downgradient soil seepage. However, when assessing the soil attenuation process, the impact of sorption competitors and the lability of adsorbed elements should first be considered. PMID- 26896588 TI - Advances and perspectives on the use of CRISPR/Cas9 systems in plant genomics research. AB - Genome editing with site-specific nucleases has become a powerful tool for functional characterization of plant genes and genetic improvement of agricultural crops. Among the various site-specific nuclease-based technologies available for genome editing, the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) systems have shown the greatest potential for rapid and efficient editing of genomes in plant species. This article reviews the current status of application of CRISPR/Cas9 to plant genomics research, with a focus on loss-of-function and gain-of-function analysis of individual genes in the context of perennial plants and the potential application of CRISPR/Cas9 to perturbation of gene expression, and identification and analysis of gene modules as part of an accelerated domestication and synthetic biology effort. PMID- 26896589 TI - Towards clarifying what distinguishes cyanobacteria able to resurrect after desiccation from those that cannot: The photosynthetic aspect. AB - Organisms inhabiting biological soil crusts (BSCs) are able to cope with extreme environmental conditions including daily hydration/dehydration cycles, high irradiance and extreme temperatures. The photosynthetic machinery, potentially the main source of damaging reactive oxygen species during cessation of CO(2) fixation in desiccating cells, must be protected to avoid sustained photodamage. We compared certain photosynthetic parameters and the response to excess light of BCS-inhabiting, desiccation-tolerant cyanobacteria Leptolyngbya ohadii and Nostoc reinholdii with those observed in the "model" organisms Nostoc sp. PCC 7120, able to resurrect after mild desiccation, and Synechococcus elongatus PCC 7942 and Synechocystis sp. PCC 6803 that are unable to recover from dehydration. Desiccation-tolerant strains exhibited a transient decline in the photosynthetic rate at light intensities corresponding to the inflection point in the PI curve relating the O(2) evolution rate to light intensity. They also exhibited a faster and larger loss of variable fluorescence and profoundly faster Q(A)(-) re oxidation rates after exposure to high illumination. Finally, a smaller difference was found in the temperature of maximal thermoluminescence signal in the absence or presence of 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) than observed in "model" cyanobacteria. These parameters indicate specific functional differences of photosystem II (PSII) between desiccation tolerant and sensitive cyanobacteria. We propose that exposure to excess irradiation activates a non radiative electron recombination route inside PSII that minimizes formation of damaging singlet oxygen in the desiccation-tolerant cyanobacteria and thereby reduces photodamage. PMID- 26896591 TI - Mucin-type core 1 glycans regulate the localization of neuromuscular junctions and establishment of muscle cell architecture in Drosophila. AB - T antigen (Galbeta1-3GalNAcalpha1-Ser/Thr), a core 1 mucin-type O-glycan structure, is synthesized by Drosophila core 1 beta1,3-galactosyltrasferase 1 (dC1GalT1) and is expressed in various tissues. We previously reported that dC1GalT1 synthesizes T antigen expressed in hemocytes, lymph glands, and the central nervous system (CNS) and that dC1GalT1 mutant larvae display decreased numbers of circulating hemocytes and excessive differentiation of hematopoietic stem cells in lymph glands. dC1GalT1 mutant larvae have also been shown to have morphological defects in the CNS. However, the functions of T antigen in other tissues remain largely unknown. In this study, we found that glycans contributed to the localization of neuromuscular junction (NMJ) boutons. In dC1GalT1 mutant larvae, NMJs were ectopically formed in the cleft between muscles 6 and 7 and connected with these two muscles. dC1GalT1 synthesized T antigen, which was expressed at NMJs. In addition, we determined the function of mucin-type O glycans in muscle cells. In dC1GalT1 mutant muscles, myofibers and basement membranes were disorganized. Moreover, ultrastructural defects in NMJs and accumulation of large endosome-like structures within both NMJ boutons and muscle cells were observed in dC1GalT1 mutants. Taken together, these results demonstrated that mucin-type O-glycans synthesized by dC1GalT1 were involved in the localization of NMJ boutons, synaptogenesis of NMJs, establishment of muscle cell architecture, and endocytosis. PMID- 26896590 TI - Generation and analysis of an improved Foxg1-IRES-Cre driver mouse line. AB - Foxg1 expression is highly restricted to the telencephalon and other head structures in the early embryo. This expression pattern has been exploited to generate conditional knockout mice, based on a widely used Foxg1-Cre knock-in line (Foxg1(tm1(cre)Skm)), in which the Foxg1 coding region was replaced by the Cre gene. The utility of this line, however, is severely hampered for two reasons: (1) Foxg1-Cre mice display ectopic and unpredictable Cre activity, and (2) Foxg1 haploinsufficiency can produce neurodevelopmental phenotypes. To overcome these issues, we have generated a new Foxg1-IRES-Cre knock-in mouse line, in which an IRES-Cre cassette was inserted in the 3'UTR of Foxg1 locus, thus preserving the endogenous Foxg1 coding region and un-translated gene regulatory sequences in the 3'UTR, including recently discovered microRNA target sites. We further demonstrate that the new Foxg1-IRES-Cre line displays consistent Cre activity patterns that recapitulated the endogenous Foxg1 expression at embryonic and postnatal stages without causing defects in cortical development. We conclude that the new Foxg1-IRES-Cre mouse line is a unique and advanced tool for studying genes involved in the development of the telencephalon and other Foxg1-expressing regions starting from early embryonic stages. PMID- 26896587 TI - Adrenaline: insights into its metabolic roles in hypoglycaemia and diabetes. AB - Adrenaline is a hormone that has profound actions on the cardiovascular system and is also a mediator of the fight-or-flight response. Adrenaline is now increasingly recognized as an important metabolic hormone that helps mobilize energy stores in the form of glucose and free fatty acids in preparation for physical activity or for recovery from hypoglycaemia. Recovery from hypoglycaemia is termed counter-regulation and involves the suppression of endogenous insulin secretion, activation of glucagon secretion from pancreatic alpha-cells and activation of adrenaline secretion. Secretion of adrenaline is controlled by presympathetic neurons in the rostroventrolateral medulla, which are, in turn, under the control of central and/or peripheral glucose-sensing neurons. Adrenaline is particularly important for counter-regulation in individuals with type 1 (insulin-dependent) diabetes because these patients do not produce endogenous insulin and also lose their ability to secrete glucagon soon after diagnosis. Type 1 diabetic patients are therefore critically dependent on adrenaline for restoration of normoglycaemia and attenuation or loss of this response in the hypoglycaemia unawareness condition can have serious, sometimes fatal, consequences. Understanding the neural control of hypoglycaemia-induced adrenaline secretion is likely to identify new therapeutic targets for treating this potentially life-threatening condition. PMID- 26896593 TI - Transabdominal cerclage: preconceptual versus first trimester insertion. AB - OBJECTIVE: Transabdominal cerclage (TAC) is an effective intervention to prevent spontaneous mid-trimester loss and preterm delivery when a transvaginal cerclage has failed. A TAC may be inserted during the first trimester of pregnancy or preconceptually. The objective of this study was to determine whether or not preconceptual transabdominal cerclage (TAC) confers any benefit over first trimester TAC insertion in terms of associated surgical and pregnancy-related morbidity and subsequent pregnancy outcome. STUDY DESIGN: This was a retrospective and prospective cohort study of 161 consecutive women who underwent preconceptual (PC) TAC versus first trimester (T1) TAC over a 22-year period from January 1993 to January 2015 at a tertiary referral miscarriage clinic. Data was obtained from case note review retrospectively from 1993 to 2006 and prospectively between 2006 and 2015. Inclusion criteria comprised a history of at least one previous spontaneous mid-trimester loss coupled with at least one failed transvaginal cerclage and screening for antiphospholipid syndrome and bacterial vaginosis. Of 144 patients who conceived, 121 had complete pregnancy outcomes; 62 in the preconceptual group and 59 in the first trimester group. Both groups had similar previous pregnancy losses and previous transvaginal cerclage history. RESULTS: Successful pregnancies >24 weeks occurred in 97% of PC TACs compared to 93% in the T1 group. Furthermore, a successful pregnancy >34 weeks occurred in 90% (56/62) in the PC group compared to 74% (44/59) in the T1 group (OR 3.18; CI 1.14-8.8). Significantly fewer patients needed emergency caesarean section for preterm delivery in the PC group (7/62 (12%) versus 21/59 (36%); OR 4.34; CI 1.68-11.32). All 6 failures before 24 weeks gestation (T1=4, PC=2) were associated with antiphospholipid syndrome or bacterial vaginosis. In the T1 group 3/65 (5%) of patients suffered serious surgical complications and haemorrhage >500mls occurred in 32/65(50%) of cases whereas no surgical complications occurred in the PC group. CONCLUSIONS: Preconceptual TAC is more successful in preventing repeat spontaneous mid-trimester loss and preterm labour, and is associated with less surgical and pregnancy-related morbidity compared to first trimester TAC insertion. PMID- 26896592 TI - Mutagenesis of GATA motifs controlling the endoderm regulator elt-2 reveals distinct dominant and secondary cis-regulatory elements. AB - Cis-regulatory elements (CREs) are crucial links in developmental gene regulatory networks, but in many cases, it can be difficult to discern whether similar CREs are functionally equivalent. We found that despite similar conservation and binding capability to upstream activators, different GATA cis-regulatory motifs within the promoter of the C. elegans endoderm regulator elt-2 play distinctive roles in activating and modulating gene expression throughout development. We fused wild-type and mutant versions of the elt-2 promoter to a gfp reporter and inserted these constructs as single copies into the C. elegans genome. We then counted early embryonic gfp transcripts using single-molecule RNA FISH (smFISH) and quantified gut GFP fluorescence. We determined that a single primary dominant GATA motif located 527bp upstream of the elt-2 start codon was necessary for both embryonic activation and later maintenance of transcription, while nearby secondary GATA motifs played largely subtle roles in modulating postembryonic levels of elt-2. Mutation of the primary activating site increased low-level spatiotemporally ectopic stochastic transcription, indicating that this site acts repressively in non-endoderm cells. Our results reveal that CREs with similar GATA factor binding affinities in close proximity can play very divergent context dependent roles in regulating the expression of a developmentally critical gene in vivo. PMID- 26896594 TI - Aberrantly expressed long noncoding RNAs in the eutopic endometria of patients with uterine adenomyosis. AB - OBJECTIVE: Adenomyosis is a common gynecologic disease. Alterations in the eutopic endometria might play an important role in the pathogenesis of adenomyosis. Long non-coding RNA (lncRNA) represents key regulators of gene expression. Our goal was to identify differentially expressed long noncoding RNA and messenger RNA (mRNA) in the eutopic endometria of subjects with adenomyosis on a genome-wide scale. STUDY DESIGN: The expression level of lncRNAs and mRNAs in the eutopic endometria from women with adenomyosis and from that of normal control subjects were detected by Affymetrix Human Transcriptome Array 2.0. Bioinformatics analysis was done for further investigation. Three up-regulated and three down-regulated lncRNAs were randomly chosen for validation by quantitative real-time polymerase chain reaction. RESULTS: A total of 165 lncRNAs and 612 mRNAs were aberrantly expressed in the eutopic endometria of subjects with adenomyosis. Pathway analysis indicated that 40 pathways corresponded to up regulated transcripts and 39 pathways corresponded to downregulated transcripts. A list of genes that might play roles in the pathogenesis of adenomyosis were produced by comparing the difference between co-expression networks. Expression of six chosen lncRNAs was validated by quantitative real-time polymerase chain reaction. CONCLUSION: This study show for the first time that the lncRNA expression profile is altered in women with adenomyosis and provides new biological foundations for further mechanistic studies in this enigmatic disorder. PMID- 26896595 TI - 50% dextrose versus normal saline as distension media during cystoscopy for assessment of ureteric patency. AB - OBJECTIVE: To compare the visualization of ureteric jets when using 50% dextrose (D50) as opposed to normal saline (NS) as distension media during cystoscopy. STUDY DESIGN: Cross sectional study. METHODS: Two patients each had two cystoscopy videos recorded at the time of a ureteric jet; one using NS and the other using D50 resulting in two sets of paired videos (four videos). A fifth cystoscopy video was recorded, as a control, at a time when there was no ureteric jet. Fifty participants including attending physicians, residents and medical students were recruited at an academic-affiliated community hospital. Participants were blinded to the medium used and viewed each of the five videos. Participants assessed each video for presence of a ureteric-jet, ease of interpretation, and compared the paired D50 and NS videos for clarity of ureteric jets. MAIN OUTCOME MEASURES: Participant's assessment of clarity of the ureteric jets when D50 was used as compared to when NS was used in the paired videos. RESULTS: All 100 observations of the two D50 videos with jets identified the presence of a jet; for the NS videos, 96/100 observations identified a jet, 2/100 did not identify a jet and 2/100 were unsure. 48/50 observations of the video with no jet were correct, while 2/50 were unsure. Participants rated the ureteric jets to be clearer in videos with D50 (86% vs 14%, P<0.001); and had difficulty interpreting cystoscopy videos with NS (62% vs 2%, OR: 80, 95% CI: 10.2-627.6). CONCLUSION: Participants preferred the clarity of the ureteric-jet when 50% dextrose was used as the distension medium during cystoscopy as compared to normal saline. PMID- 26896597 TI - Elevated serum gamma-glutamyltransferase predicts advanced histological liver damage in chronic hepatitis B. AB - Recently, several studies have demonstrated that serum gamma-glutamyltransferase (GGT) is associated with some diseases, such as chronic hepatitis B (CHB). This study investigates the association between GGT levels and liver pathological grading in patients with CHB. 300 patients with CHB who underwent liver biopsy were enrolled. Histological assessment was based on the Scheuer scoring system. Univariate and multivariate analyses were performed to evaluate the independent predicting factors for the presence of liver pathological grade in patients with CHB. In patients with CHB, the mean GGT level was 44.14+/-3.69 (U/L) in low activity group and 114.87+/-15.75 (U/L) in the high activity group (p<0.001). Also, there was significant difference between the low and high fibrosis group with regard to GGT levels [45.32+/-4.64 (U/L) vs. 90.41+/-11.06 (U/L), p<0.001, respectively]. The variables that were significant in the univariate analysis were evaluated in multivariate logistic regression analysis, and GGT was an independent predicting factor of necroinflammation and fibrosis (OR=1.007, 95%CI: 1.001-1.014, p=0.030; OR=1.009, 95%CI: 1.003-1.014, p=0.003, respectively). Results of this study suggest that GGT is a new non-invasive marker that can be used to predict advanced histological liver damage. PMID- 26896598 TI - ELISA index of serum fucosylated haptoglobin for diagnosis of HCC using the normal and reverse AAL ELISA. AB - Aberrant glycosylation of target glycoprotein is a frequent and significant event involved in many cancers, for example, increased fucosylated haptoglobin (Hp) in hepatocellular carcinoma (HCC). The normal and reverse Aleuria aurantia lectin (AAL) ELISA were used to measure fucosylated Hp in 98 HCC patients and 98 healthy controls. Simultaneously, protein ELISA was used to measure its protein expression. ELISA Index (OD value of fucosylated Hp/OD value of protein Hp) was developed to reflect Hp fucosylation level on its protein level (Fuc-Hp). Normal ELISA Index exhibited an area under the ROC curve (AUC) of 0.727 with sensitivity of 61.22%, specificity of 81.63%, and accuracy of 71.43% in distinguishing HCC from healthy controls. AUC of reverse ELISA Index was 0.836 with 68.36% of sensitivity, 95.92% of specificity, and 82.14% of accuracy. Thus, AAL ELISA, especially the reverse AAL ELISA, is a promising technology to evaluate diagnostic potential of serum glycoprotein. Fuc-Hp could serve as a useful glycobiomarker for the diagnosis and prediction of HCC. PMID- 26896596 TI - Biomaterials for enhancing anti-cancer immunity. AB - Cancer immunotherapy is becoming a standard approach to treat many cancers. However, shortcomings of current methods limit therapeutic benefit in many patients. Rationally designed biomaterial strategies to deliver immune modulatory drugs can potentially show improved safety profiles, while providing multifunctional and spatiotemporally controlled signals to immune cells to improve their anti-cancer activity. This brief review describes biomaterials based strategies that enhance immune cell function at various tissue sites to improve anti-cancer immunity. Continued collaboration between bioengineers, immunologists, industry, and clinicians is required for biomaterial-based immunotherapy strategies to continue moving to the clinic. PMID- 26896599 TI - Increase of infiltrating monocytes in the livers of patients with chronic liver diseases. AB - Infiltrating monocytes have been demonstrated to contribute to tissue damage in experimental models of liver injury and fibrosis. However, less is known about monocyte infiltration in the livers of patients with chronic liver diseases (CLD). In the present study, we demonstrated that CD68+ hepatic macrophages and MAC387+ infiltrating monocytes were significantly increased in the livers of CLD patients with different etiologies as compared with normal liver tissue. In addition, CLD patients with higher inflammatory grading scores had more CD68+ macrophages and MAC387+ monocytes infiltration in their livers compared to those with lower scores. Significantly more MAC387+ infiltrating monocytes were found in the liver tissue of CLD patients with higher fibrotic staging scores compared to those with lower scores. Monocyte chemoattractant protein-1 (MCP-1) expression was significantly increased in the livers of CLD patients with different etiologies. MCP-1 staining scores were significantly positively associated with the numbers of MAC387+ infiltrating monocytes in CLD patients. Taken together, our results demonstrate that infiltrating monocytes may play a pathological role in exacerbating chronic liver inflammation and fibrosis in CLD. MCP-1 may be involved in the monocyte infiltration and progression of liver inflammation and fibrosis in CLD. PMID- 26896600 TI - The oral and craniofacial relevance of chemically modified RNA therapeutics. AB - Several tissue engineering strategies in the form of protein therapy, gene therapy, cell therapy, and their combinations are currently being explored for oral and craniofacial regeneration and repair. Though each of these approaches has advantages, they all have common inherent drawbacks of being expensive and raising safety concerns. Using RNA (encoding therapeutic protein) has several advantages that have the potential to overcome these limitations. Chemically modifying the RNA improves its stability and mitigates immunogenicity allowing for the potential of RNA to become an alternative to protein and gene based therapies. This brief review article focuses on the potential of RNA therapeutics in the treatment of disorders in the oral and craniofacial regions. PMID- 26896602 TI - Assessment and management of advanced adrenocortical carcinoma using a precision oncology care model. AB - Within the category of orphan diseases and rare malignancies, adrenocortical carcinoma (ACC) represents an aggressive entity with high mortality and morbidity. While localized tumors which are diagnosed early can be cured with surgical intervention, there are prognostic factors which predict for micrometastases and consequent recurrent and advanced disease. In such cases, cytotoxic chemotherapy and mitotane have been utilized with a very modest degree of benefit. The poor prognosis of recurrent and advanced ACC has underscored the interest in nuanced characterization of ACC cases using next-generation sequencing (NGS)-based genomic and other '-omic' profiling to guide the precision medicine approach and personalized use of targeted and novel therapies. PMID- 26896601 TI - The potential for tumor suppressor gene therapy in head and neck cancer. AB - Head and neck squamous cell carcinoma remains a highly morbid and fatal disease. Importantly, genomic sequencing of head and neck cancers has identified frequent mutations in tumor suppressor genes. While targeted therapeutics increasingly are being investigated in head and neck cancer, the majority of these agents are against overactive/overexpressed oncogenes. Therapy to restore lost tumor suppressor gene function remains a key and under-addressed niche in trials for head and neck cancer. Recent advances in gene editing have captured the interest of both the scientific community and the public. As our technology for gene editing and gene expression modulation improves, addressing lost tumor suppressor gene function in head and neck cancers is becoming a reality. This review will summarize new techniques, challenges to implementation, future directions, and ethical ramifications of gene therapy in head and neck cancer. PMID- 26896603 TI - Genome editing systems in novel therapies. AB - Genome editing is the process in which DNA sequences at precise genomic locations are modified. In the past three decades, genome editing by homologous recombination has been successfully performed in mouse for generating genetic models. The low efficiency of this process in human cells, however, had prevented its clinical application until the recent advancements in designer endonuclease technologies. The significantly improved genome editing efficiencies aided by ZFN, TALEN, and CRISPR systems provide unprecedented opportunities not only for biomedical research, but also for developing novel therapies. Applications based on these genome editing tools to disrupt deleterious genes, correct genetic mutations, deliver functional transgenes more effectively or even modify the epigenetic landscape are being actively investigated for gene and cell therapy purposes. Encouraging results have been obtained in limited clinical trials in the past two years. While most of the applications are still in proof-of principle or preclinical development stages, it is anticipated that the coming years will see increasing clinical success in novel therapies based on the modern genome editing technologies. It should be noted that critical issues still remain before the technologies can be translated into more reliable therapies. These key issues include off-target evaluation, establishing appropriate preclinical models and improving the currently low efficiency of homology-based precise gene replacement. In this review we discuss the preclinical and clinical studies aiming at translating the genome editing technologies as well as the issues that are important for more successful translation. PMID- 26896604 TI - Targeting the cyclin D-cyclin-dependent kinase (CDK) 4/6-retinoblastoma pathway with selective CDK 4/6 inhibitors in hormone receptor-positive breast cancer: rationale, current status, and future directions. AB - Dysregulation of the cyclin D-cyclin-dependent kinase (CDK) 4/6-INK4 retinoblastoma (Rb) pathway is an important contributor to endocrine therapy resistance. Recent clinical development of selective inhibitors of CDK4 and CDK6 kinases has led to renewed interest in cell cycle regulators, following experience with relatively non-selective pan-CDK inhibitors that often resulted in limited activity and poor safety profiles in the clinic. The highly selective oral CDK 4/6 inhibitors palbociclib (PD0332991), ribociclib (LEE011), and abemaciclib (LY2835219) are able to inhibit the proliferation of Rb-positive tumor cells and have demonstrated dose-dependent growth inhibition in ER+ breast cancer models. In metastatic breast cancer, all three agents are being explored in combination with endocrine therapy in Phase III studies. Results so far indicated promising efficacy and manageable safety profiles, and led to the FDA approval of palbociclib. Phase II-III studies of these agents, in combination with endocrine therapy, are also underway in early breast cancer in the neoadjuvant and adjuvant settings. Selective CDK 4/6 inhibitors are also being investigated with other targeted agents or chemotherapy in the advanced setting. This article reviews the rationale for targeting cyclin D-CDK 4/6 in hormone receptor-positive (HR+) breast cancer, provides an overview of the available preclinical and clinical data with CDK 4/6 inhibitors in breast cancer to date, and summarizes the main features of ongoing clinical trials of these new agents in breast cancer. Future trials evaluating further combination strategies with CDK 4/6 backbone and translational studies refining predictive biomarkers are needed to help personalize the optimal treatment regimen for individual patients with ER+ breast cancer. PMID- 26896605 TI - The class-dimensional structure of PTSD before and after deployment to Iraq: Evidence from direct comparison of dimensional, categorical, and hybrid models. AB - The assumption of specific etiology in posttraumatic stress disorder (PTSD) differentiates the disorder from most other psychiatric conditions. A 'risky test' of the assumption of specific etiology and resultant trauma-related symptom dimensions was conducted through structural modeling of PTSD symptoms in soldiers before (N=522) and after (n=423) a combat deployment to Iraq. If PTSD represents a discrete diagnostic entity that emerges after trauma exposure, we hypothesized either the number of latent classes should increase from pre- to post-deployment or symptom dimensions should qualitatively distinguish affected from unaffected classes following trauma exposure. Comparison of latent structural models revealed best fitting hybrid models for PTSD and depression with strong invariance of symptom dimensions across classes both before and after deployment and only quantitative (i.e., severity) differences between classes. These findings suggest PTSD is generally well-conceptualized as a dimensional syndrome worsened but not necessarily elicited by trauma exposure. PMID- 26896606 TI - Red cell distribution width is a predictor of ST resolution and clinical outcome following thrombolysis in acute ST elevation myocardial infarction. AB - INTRODUCTION: Red cell distribution width (RDW) has been shown to associate with adverse outcomes in various cardiovascular diseases. We aimed to explore the predictive value of RDW for resolution of the ST segment (STR) after thrombolytic therapy in patients with ST elevation myocardial infarction (STEMI). METHODS: Patients with STEMI with indication for thrombolytic therapy were recruited from a university center between 2013 and 2015. A comprehensive laboratory investigation at the time of admission included measurement of RDW. Following thrombolysis ST segment resolution was assessed after 90 min. A positive response (STR >= 50%) was the primary endpoint. Secondary endpoints were major adverse cardiac events (MACE) defined as occurrence of acute heart failure, ventricular dysrhythmia beyond the first 24h, cardiac arrest or death during hospitalization. RESULTS: A total of 312 patients (271 male) with the mean age of 57.9 +/- 12.3 were enrolled. RDW on admission was 14.1 +/- 1.0% (range: 11.6-17.7%). STR was seen in 191 cases (61.2%). MACE occurred in 36 (11.5%) patients. The long-term mortality rate was 7.1% during the follow-up period of 7.7 +/- 3.2 months. Even after adjusting for co-morbid conditions, in multivariate model, baseline RDW, independently predicts STR (RR=2.46, 95% CI 1.32-4.57, P=0.005) and in hospital occurrence of MACE (RR=3.17, 95% CI 1.23-8.46, p=0.017). The cut-off values for RDW in predicting STR and MACE were 14.2% and 14.4%, respectively. CONCLUSION: An elevated baseline RDW could predict adverse outcomes and response to thrombolytic therapy in patients with STEMI. This extends our knowledge about RDW value in prognostication. PMID- 26896608 TI - A sustained decrease in plasma fibrinolytic potential following partial liver resection or pancreas resection. AB - BACKGROUND: Patients undergoing partial hepatectomy have a substantial risk for postoperative venous thrombosis even in the presence of optimal thromboprophylaxis. Recently we demonstrated a hypercoagulable state following a partial hepatectomy which was related to decreased plasma levels of natural anticoagulants and elevated levels of FVIII. The fibrinolytic status following partial hepatectomy has not been studied, but may display unique features as a result of temporarily decreased synthesis of fibrinolytic proteins. METHODS: We included 17 patients undergoing a partial hepatectomy and determined plasma fibrinolytic potential and measured plasma levels of individual fibrinolytic proteins in serial samples taken perioperatively. Results were compared to ten patients undergoing pancreas resection and twenty-four healthy volunteers. RESULTS AND CONCLUSION: Following both partial hepatectomy and pancreas resection plasma fibrinolytic potential decreased at the end of surgery, normalized on post operative day 1, and decreased again on post-operative day 3 after which the hypofibrinolytic state gradually resolved. The hypofibrinolytic state on day 1 associated with increased plasma levels of PAI-1 in both groups. Plasma levels of plasminogen, alpha2-antiplasmin and TAFI all decreased following partial hepatectomy and pancreas resection and levels recovered over time. The kinetics of recovery were different for the different proteins and were slower in the liver resection group, resulting in a unique ratio of pro-to-anti-fibrinolytic proteins at each time point. This may explain the hypofibrinolytic status from day 3 onwards. A sustained plasma hypofibrinolytic state in combination with the hypercoagulable state we previously identified may contribute to the increased risk of thrombotic complications after partial liver resection. PMID- 26896607 TI - Plasminogen activator inhibitor and the risk of cardiovascular disease: The Framingham Heart Study. AB - INTRODUCTION: Although plasminogen activator inhibitor (PAI-1) plays a key regulatory role in fibrinolysis, it has not been clearly shown to independently predict cardiovascular disease (CVD) among individuals without prior CVD. We investigated, in the Framingham Heart Study offspring cohort, whether PAI-1 predicted CVD risk among individuals without prior CVD. METHODS: Plasma PAI-1 antigen and tissue plasminogen activator (TPA) antigen were measured in 3203 subjects without prior CVD between 1991 and 1995; average follow-up of 10 years. PAI-1 was remeasured 4 years after baseline, to determine the effect of serial change on risk. RESULTS: PAI-1 levels (mean +/- SD) were 29.1 ng/ml (19.2) versus 22.1 (16.5) for those and without incident CVD; p<0.001, and TPA levels were 12.0 ng/ml (5.7) versus 9.0 (4.7); p<0.001. PAI-1 and TPA antigen levels had a strong unadjusted linear relation with incident CVD (p<0.001). After adjustment for conventional risk factors, the hazard ratios (HRs) for higher quartiles of PAI-1, compared with the lowest, were 1.9, 1.9, 2.6 (linear trend p=0.006), and 1.6, 1.6, 2.9 (p<0.001) for TPA antigen. The adjusted HRs for increasing quartiles of serial change in PAI-1 at 4 years, compared with the lowest, were 0.9, 0.8, 1.3 (p=0.050). C statistic assessment showed that adding PAI-1 or TPA to conventional risk factors resulted in small increases in discrimination and modest reclassification of risk, which was statistically significant for TPA (net reclassification 6.8%, p=0.037) but not PAI-1 (4.8%, p=0.113). CONCLUSION: PAI-1 and TPA antigen levels are predictive of CVD events after accounting for established risk factors. A serial increase in PAI-1 is associated with a further increase in risk. These findings support the importance of fibrinolytic potential in CVD. PMID- 26896609 TI - Radiosynovectomy in haemophilic synovitis of elbows and ankles: Is the effectiveness of yttrium-90 and rhenium-186 different? AB - BACKGROUND: Radiosynovectomy (RS) reduces the number of haemarthroses and the synovial size in chronic haemophilic synovitis. The purpose of this study was to quantitatively compare the effectiveness of two types of RS (yttrium-90 vs. rhenium-186) in terms of the objective improvement of haemarthroses and synovial size. METHODS: Seventy RSs were performed in 70 joints (44 elbows, 26 ankles) of 70 haemophiliacs diagnosed with chronic synovitis. Yttrium-90 was used in 21 joints and rhenium-186 was used in 49 joints. The mean patient age was 20.61 years. RESULTS: RS resulted in significant improvement in the three variables studied (six months before RS vs. six months after RS), namely in the number of episodes of haemarthrosis (67.8% improvement); the size of the synovium as measured by means of a clinical scale (43.8% improvement) and imaging techniques in millimetres (26.7% improvement). We did not find significant statistical differences between yttrium-90 and rhenium-186 regarding their efficacy. No correlation was found between the results and other variables: age, joint (ankle or elbow), presence or absence of radiological involvement, type of haemophilia (A or B), grade of haemophilia (mild, moderate or severe), previous haematological treatment (on demand or prophylaxis), and the presence or absence of inhibitor CONCLUSIONS: Yttrium-90 RS and rhenium-186 RS were equally effective in reducing the number of haemarthroses and the size of the synovium in ankles and elbows in the short-term (6 months). No correlation was found between the results and other patients' characteristics. PMID- 26896610 TI - A theranostic micelleplex co-delivering SN-38 and VEGF siRNA for colorectal cancer therapy. AB - The development of an efficient colorectal cancer therapy is currently a public health priority. In the present work, we proposed a multifunctional theranostic micellar drug delivery system utilizing cationic PDMA-block-poly(epsilon caprolactone) (PDMA-b-PCL) micelles as nanocarriers of SN-38 (7-ethyl-10 hydroxycamptothecin), ultra-small superparamagnetic iron oxide nanoparticles (USPIO), and small interfering RNA (siRNA) that targets human vascular endothelial growth factor (VEGF). The VEGF siRNA was conjugated to polyethylene glycol (PEG) (siRNA-PEG) before complexation with the micelles in order to improve the siRNA's stability and to prolong its retention time in the blood circulation. To further improve the in vivo biosafety, we prepared mixed micelles using mPEG-PCL together with PDMA-b-PCL copolymer. The SN-38/USPIO-loaded siRNA PEG mixed micelleplexes passively targeted to tumor regions and synergistically facilitated VEGF silencing and chemotherapy, thus efficiently suppressing tumor growth via a multi-dose therapy regimen. Additionally, the SN-38/USPIO-loaded siRNA-PEG mixed micelleplexes acted as a negative magnetic resonance imaging (MRI) contrast agent in T2-weighted imaging, resulting in a powerful tool for the diagnosis and for tracking of the therapeutic outcomes. In summary, we established a theranostic micellar drug and gene delivery system that not only synergistically combined gene silencing and chemotherapy but also served as a negative MRI contrast agent, which reveal its potential as a novel colorectal cancer therapy. PMID- 26896612 TI - High glucose regulates LN expression in human liver sinusoidal endothelial cells through ROS/integrin alphavbeta3 pathway. AB - Diabetes mellitus can cause a wide variety of vascular complications and is one of the major risk factors for Non Alcoholic Fatty Liver Disease (NAFLD). The present study was designed investigate the expression of laminin (LN) in human liver sinusoidal endothelial cells (HLSECs) induced by high glucose and the role of reactive oxygen species (ROS) and integrin alphavbeta3 in the regulation of LN expression. HLSECs were cultured and treated with media containing 25 mM glucose in the presence or absence of N-acetylcysteine (NAC) or clone LM609. The level of intracellular ROS of HLSECs was measured with 2',7' dichloro-fluorescein diacetate (DCFH-DA) probe. Expression of integrin alphavbeta3 was measured using RT-PCR and Western blot. Expression of LN was testified by immunofluorescence assay. Compared with that in control group, ROS level and the expression of integrin alphavbeta3 and LN increased in high glucose group. Compared with that in high glucose group, antioxidant NAC inhibited the expression of integrin alphavbeta3, NAC and the anti-body for blocking integrin alphavbeta3 (clone LM609) down-regulated the expression of LN. However, the above parameters did not differ between control and mannitol groups. High glucose up-regulates expression of LN in HLSECs through ROS/integrin alphavbeta3 pathway. PMID- 26896613 TI - Endocarditis due to Acinetobacter baumannii. PMID- 26896611 TI - Levetiracetam attenuates rotenone-induced toxicity: A rat model of Parkinson's disease. AB - Levetiracetam (LEV), a second-generation anti-epileptic drug, is used for treatment of both focal and generalized epilepsy. Growing body of evidence suggests that LEV may have neuroprotective effects. The present study was undertaken to investigate the neuroprotective effects of LEV on rotenone-induced Parkinson's disease (PD) in rats. Twenty-four adult Sprague-Dawley rats were infused with rotenone (3 MUg/MUl in DMSO) or vehicle (1 MUl DMSO) into the left substantia nigra pars compacta (SNc) under stereotaxic surgery. PD model was assessed by rotational test ten days after drug infusion. The valid PD rats were randomly distributed into two groups; Group 1 (n=8) and Group 2 (n=8) were administered saline (1 ml/kg/day, i.p.) and LEV (600 mg/kg/day, i.p.) through 21 days, respectively. The effects of LEV treatment were evaluated by behavioral (rotation score), biochemical (brain homovalinic acid level and oxidant/antioxidant status) and immunohistochemical (tyrosine hydroxylase) parameters. Apomorphine-induced rotations in PD rats were significantly suppressed by LEV treatment. While unilateral rotenone lesion induced a dramatic loss of dopaminergic neurons both in the striatum and SNc, LEV treatment significantly attenuated the degenerative changes in dopaminergic neurons. Furthermore, LEV significantly decreased lipid peroxide levels, a marker of lipid peroxidation, and induced glutathione levels, catalase and superoxide dismutase activity in PD rats compared with saline group. We conclude that LEV may have beneficial effects on dopaminergic neurons against rotenone-induced injury. The underlying mechanism may be associated with the attenuation of oxidative stress. PMID- 26896614 TI - Electrocardiogram in a patient with "acute intermittent porphyria"-triggered Takotsubo syndrome. PMID- 26896615 TI - Healthy aging and myocardium: A complicated process with various effects in cardiac structure and physiology. AB - It is known that there is an ongoing increase in life expectancy worldwide, especially in the population older than 65years of age. Cardiac aging is characterized by a series of complex pathophysiological changes affecting myocardium at structural, cellular, molecular and functional levels. These changes make the aged myocardium more susceptible to stress, leading to a high prevalence of cardiovascular diseases (heart failure, atrial fibrillation, left ventricular hypertrophy, coronary artery disease) in the elderly population. The aging process is genetically programmed but modified by environmental influences, so that the rate of aging can vary widely among people. We summarized the entire data concerning all the multifactorial changes in aged myocardium and highlighting the recent evidence for the pathophysiological basis of cardiac aging. Keeping an eye on the clinical side, this review will explore the potential implications of the age-related changes in the clinical management and on novel therapeutic strategies potentially deriving from the scientific knowledge currently acquired on cardiac aging process. PMID- 26896616 TI - Progression of calcification after implantation of a fully bioresorbable scaffold: A serial and combined IVUS-OCT follow-up of 5years. PMID- 26896617 TI - Kounis syndrome: Identifying the trigger. PMID- 26896618 TI - Comparative effectiveness and safety of non-vitamin K antagonist oral anticoagulants versus warfarin in patients with atrial fibrillation and valvular heart disease. PMID- 26896619 TI - Novel composite score to predict atrial Fibrillation in acute stroke patients: AF predicting score in acute stroke. AB - BACKGROUND AND PURPOSE: Identification of high risk population for atrial fibrillation among acute stroke patients is a center of attention. The objective of the present study was to construct a model that can predict the presence of atrial fibrillation in ischemic stroke patients and to validate the model. METHODS: From a prospectively collected hospital-based stroke registry participated by two hospital, we selected data of patients who were admitted within 24 h after the onset of symptoms. Using a dataset of 1355 acute ischemic stroke patients, a model to predict the presence of atrial fibrillation was constructed and the probability of the presence of atrial fibrillation (AF probability) was calculated. The patients were classified into low-risk, moderate risk, and high-risk groups according to AF-probability. The performance of the model to predict atrial fibrillation among acute stroke patients was investigated and validated. RESULTS: Seven factors were selected as constituents of the model including age, left atrial size, free fatty acid level, triglyceride level, susceptibility vessel sign, hemorrhagic transformation, and cortical involvement. The performance of the model was excellent, with a C-statistic of 0.908 (95% confidence interval 0.887-0.930). According to risk group, true positivity for atrial fibrillation was 4.3%, 36.5%, 91.2% in the low-risk, moderate-risk, and high-risk groups, respectively. The internal and external validation test showed stable consistency of the model. CONCLUSION: The model constructed in this study could stratify stroke patients according to their risk of AF and may be helpful for selecting candidates who need extensive cardiac monitoring. PMID- 26896620 TI - Acute myocardial infarction due to paradoxical embolism. PMID- 26896621 TI - Response to the letter "No evidence to support high-intensity statin in Chinese patients with coronary heart disease". PMID- 26896622 TI - Low procedure-related mortality achieved with alcohol septal ablation in European patients. PMID- 26896623 TI - Takotsubo cardiomyopathy systematic review: Pathophysiologic process, clinical presentation and diagnostic approach to Takotsubo cardiomyopathy. AB - Takotsubo cardiomyopathy (TTC) is characterized by transient left ventricular apical ballooning with the absence of coronary occlusion, which typically occurs in older women after emotional or physical stress. The pathophysiology of TTC is not well established, though several possible causes such as catecholamine cardiotoxicity, metabolic disturbance, coronary microvascular impairment and multivessel epicardial coronary artery spasm have been proposed. A number of diagnostic criteria have been suggested in the world and not unified as single, but the most common accepted one is Mayo Clinic proposed criteria. Since the clinical presentation of TTC is usually similar to acute coronary syndrome, differential diagnosis is essential to exclude other diseases and also for its treatment. Imaging modality including echocardiogram, angio CT and cardiac MRI, and lab tests for catecholamine, troponin T, creatine kinase MB and B-type natriuretic peptide can be useful to differentiate TTC from other diseases. Prognosis is generally favorable and in-hospital mortality is from 0% to within 10%. PMID- 26896624 TI - Scaffold thrombosis: Exaggerated illusion, or when statistics rules. PMID- 26896625 TI - Intracardiac ectopic liver mimicking atrial myxoma--An unusual cause for a right atrial mass. PMID- 26896626 TI - A new policy by attending specialist standardization training for medical personnel. PMID- 26896628 TI - Retromer and Rab2-dependent trafficking mediate PS1 degradation by proteasomes in endocytic disturbance. AB - Accumulating evidence suggests that endocytic pathway deficits are involved in Alzheimer's disease pathogenesis. Several reports show that endocytic disturbance affects beta-amyloid peptide (Abeta) cleavage from beta-amyloid precursor protein (APP). Presenilin-1 (PS1) is the catalytic core of the gamma-secretase complex required for Abeta generation. Previously, we showed that aging induces endocytic disturbance, resulting in the accumulation of Abeta and APP in enlarged endosomes. It remains unclear, however, whether PS1 localization and function are affected with endocytic disturbance. Here, we report that in endocytic disturbance, PS1 is transported from endosomes to ER/Golgi compartments via retromer trafficking, and that PS1 interacts with vacuolar protein sorting associated protein 35 both in vitro and in vivo. Moreover, PS1 is degraded by proteasomes via a Rab2-dependent trafficking pathway, only during endocytic disturbance. These findings suggest that PS1 levels and localization in endosomes are regulated by retromer trafficking and ER-associated degradation system, even if endocytic disturbance significantly induces the endosomal accumulation of APP and beta-site APP-cleaving enzyme 1. Results of this study also suggest that retromer deficiency can affect PS1 localization in endosomes, where Abeta cleavage mainly occurs, possibly leading to enhanced Abeta pathology. We proposed the following mechanism for intracellular transport of presenilin-1 (PS1). When endosome/lysosome trafficking is disturbed, PS1 is transported from endosome to endoplasmic reticulum (ER)/Golgi compartments via retromer and Rab2-mediated trafficking, and then degraded by endoplasmic reticulum-associated degradation (ERAD). Perturbations in this trafficking can cause abnormal endosomal accumulation of PS1, and then may lead to exacerbated Abeta pathology. Cover Image for this issue: doi: 10.1111/jnc.13318. PMID- 26896629 TI - Lesion correlates of impairments in actual tool use following unilateral brain damage. AB - To understand how the brain controls actions involving tools, tests have been developed employing different paradigms such as pantomime, imitation and real tool use. The relevant areas have been localized in the premotor cortex, the middle temporal gyrus and the superior and inferior parietal lobe. This study employs Voxel Lesion Symptom Mapping to relate the functional impairment in actual tool use with extent and localization of the structural damage in the left (LBD, N=31) and right (RBD, N=19) hemisphere in chronic stroke patients. A series of 12 tools was presented to participants in a carousel. In addition, a non-tool condition tested the prescribed manipulation of a bar. The execution was scored according to an apraxic error scale based on the dimensions grasp, movement, direction and space. Results in the LBD group show that the ventro-dorsal stream constitutes the core of the defective network responsible for impaired tool use; it is composed of the inferior parietal lobe, the supramarginal and angular gyrus and the dorsal premotor cortex. In addition, involvement of regions in the temporal lobe, the rolandic operculum, the ventral premotor cortex and the middle occipital gyrus provide evidence of the role of the ventral stream in this task. Brain areas related to the use of the bar largely overlapped with this network. For patients with RBD data were less conclusive; however, a trend for the involvement of the temporal lobe in apraxic errors was manifested. Skilled bar manipulation depended on the same temporal area in these patients. Therefore, actual tool use depends on a well described left fronto-parietal-temporal network. RBD affects actual tool use, however the underlying neural processes may be more widely distributed and more heterogeneous. Goal directed manipulation of non-tool objects seems to involve very similar brain areas as tool use, suggesting that both types of manipulation share identical processes and neural representations. PMID- 26896627 TI - Inhibition of the NLRP3 inflammasome limits the inflammatory injury following myocardial ischemia-reperfusion in the mouse. AB - BACKGROUND: Successful reperfusion is the most effective strategy to reduce ischemic injury in acute myocardial infarction (AMI). Ischemic injury, however, also triggers a secondary ischemia-independent injury, known as reperfusion injury, contributing to the overall infarct size. We hypothesize that inhibition of the Nod-like Receptor Protein-3 (NLRP3) inflammasome limits infarct size following myocardial ischemia/reperfusion (I/R), by inhibiting the inflammatory component of the reperfusion injury. METHODS: CD-1 male mice underwent transient ligation of the left anterior descending coronary artery for 30 or 75min followed by reperfusion. Infarct size was measured at 1, 3 and 24h. A NLRP3 inflammasome inhibitor (NLRP3inh) or vehicle was administrated immediately at time of reperfusion or with a delay of 1 or 3h of reperfusion. RESULTS: A time-dependent increase in infarct size was measured at 1, 3, and 24h after reperfusion (11+/ 2%, 30+/-5% and 43+/-4% of the area at risk respectively; P<0.001 for trend). NLRP3 myocardial expression was significantly increased at 24h and 6h vs 3h (P<0.01). Administration of the NLRP3inh at reperfusion did not reduce infarct size at 3h, while it significantly reduced infarct size at 24h (-56% vs vehicle, P<0.01). The NLRP3inh given 1h after reperfusion also significantly decreased caspase-1 activity and infarct size measured at 24h, whereas the NLRP3inh did not when given with a delay of 3h. CONCLUSIONS: Pharmacological inhibition of the NLRP3 inflammasome within 1h of reperfusion limits the secondary inflammatory injury and infarct size following myocardial ischemia-reperfusion in the mouse. PMID- 26896630 TI - Shedding new light on representational neglect: The importance of dissociating visual and spatial components. AB - Over the last decade, many studies have demonstrated that visuospatial working memory (VSWM) can be divided into two subsystems, dealing respectively with spatial and visual information. A similar dissociation has been observed in brain damaged patients without neglect for mental imagery skills. The first aim of the present study was to examine whether performance dissociations between spatial and visual mental imagery can be observed in unilateral neglect. The second objective was to further investigate the role of spatial and visual working memory subsystems in the mental representation abilities of neglect patients and healthy controls, and their dependence on the nature of the mental imagery tasks performed. The results showed that spatial and visual imagery processes can be selectively impaired in unilateral neglect. Spatial working memory skills were also found to strongly predict spatial imagery score in the two experimental groups. However, contrary to what was observed in healthy controls, visual working memory did not appear to predict performance on visual imagery tasks in neglect patients. Overall, these findings highlight the importance of investigating both visual and spatial components of working memory and mental imagery in neglect patients. PMID- 26896631 TI - A direct droplet digital PCR method for quantification of residual DNA in protein drugs produced in yeast cells. AB - Yeast cells, in particular Pichia pastoris, are the host cell of choice for manufacturing several protein therapeutic agents in the biopharmaceutical industry. Host cell DNA is an impurity of such manufacturing process and the residual DNA after the purification process of the drug must be monitored to ensure drug purity and safety. Currently, real-time PCR (qPCR) based methods are widely employed for quantification of host residual DNA. At the same time the digital PCR technology is coming into prominence with promise of higher sensitivity. Here we report a method where the protein drug is directly added to the droplet digital PCR (ddPCR) reaction including yeast-specific primers and fluorescent-tagged probe and nanoliter-sized droplets are generated. The droplets are then subjected to PCR followed by analysis for fluorescence. This Pichia residual DNA direct ddPCR method for yeast can be used to test higher amount of drug compared to the corresponding qPCR method thereby increasing sensitivity, retaining high precision and accuracy and has a wide linear range of determination. The method has been successfully tested with three batches of a recombinant human IgG1-Fc-based drug (RP-1) and with commercially available human insulin, both manufactured in yeast cells. This method simplifies the residual DNA quantification protocol by eliminating DNA extraction or protease digestion and eliminates use of DNA standards in day-to-day running of the method. PMID- 26896633 TI - The influence of multiple sensory impairments on functional balance and difficulty with falls among U.S. adults. AB - OBJECTIVE: Studies have looked at the individual associations of sensory impairment on balance, but no population-based studies have examined their combined association on balance and difficulty with falls. Thus, the purpose of this study was to examine both the independent associations and combined associations of visual impairment, peripheral neuropathy, and self-reported hearing loss with the odds of reporting difficulty with falls and functional balance. METHODS: Data from the 2003-2004 National Health and Nutrition Examination Survey were used. Vision and peripheral neuropathy were objectively measured, and hearing was self-reported. Balance testing consisted of a modified Romberg test. After exclusions, 1662 (40-85years of age) participants provided complete data on the study variables. RESULTS: Sensory impairment was associated with perceived difficulty of falls and functional balance. Participants who presented a single sensory impairment had 29% reduced odds of having functional balance (95% CI=0.54-0.93, p=0.01) and increased odds of reporting difficulty with falls by 61% (95% CI=0.99-2.60, p=0.05). Moreover, our multisensory models showed some evidence of a dose-response relationship, in that sensory impairment of multiple sensory systems was associated with worse balance (OR =0.59, CI=0.35 1.00, p=0.05) and perceived difficulty of falls (OR =5.02, 95% CI=1.99-12.66, p=0.002) when compared to those with less sensory impairment. CONCLUSION: Multiple sensory impairment is associated with significantly higher odds of both reporting difficulty with falls and balance dysfunction, which may lead to a subsequent fall, ultimately compromising the individual's health. PMID- 26896632 TI - Fully automated determination of nicotine and its major metabolites in whole blood by means of a DBS online-SPE LC-HR-MS/MS approach for sports drug testing. AB - Dried blood spots (DBS) represent a sample matrix collected under minimal invasive, straightforward and robust conditions. DBS specimens have been shown to provide appropriate test material for different analytical disciplines, e.g., preclinical drug development, therapeutic drug monitoring, forensic toxicology and diagnostic analysis of metabolic disorders in newborns. However, the sample preparation has occasionally been reported as laborious and time consuming. In order to minimize the manual workload and to substantiate the suitability of DBS for high sample-throughput, the automation of sample preparation processes is of paramount interest. In the current study, the development and validation of a fully automated DBS extraction method coupled to online solid-phase extraction using the example of nicotine, its major metabolites nornicotine, cotinine and trans-3'-hydroxycotinine and the tobacco alkaloids anabasine and anatabine is presented, based on the rationale that the use of nicotine-containing products for performance-enhancing purposes has been monitored by the World Anti-Doping Agency (WADA) for several years. Automation-derived DBS sample extracts were directed online to liquid chromatography high resolution/high mass accuracy tandem mass spectrometry, and target analytes were determined with support of four deuterated internal standards. Validation of the method yielded precise (CV <7.5% for intraday and <12.3% for interday measurements) and linear (r(2)>0.998) results. The limit of detection was established at 5 ng mL(-1) for all studied compounds, the extraction recovery ranged from 25 to 44%, and no matrix effects were observed. To exemplify the applicability of the DBS online-SPE LC-MS/MS approach for sports drug testing purposes, the method was applied to authentic DBS samples obtained from smokers, snus users, and e-cigarette users. Statistical evaluation of the obtained results indicated differences in metabolic behavior depending on the route of administration (inhalative versus buccal absorption) in terms of the ratio of nicotine and nornicotine. PMID- 26896634 TI - Mapping interventions that promote mental health in the general population: A scoping review of reviews. AB - Health policies and programs promoting mental health or preventing mental illness in the general public are under-recognized facets of primary prevention. Increasing awareness and adoption of such strategies could reduce the burden of mental illness in individuals, families, communities, and society as whole. We conducted a scoping review of reviews of interventions to promote mental health or prevent mental illness. We searched PubMed, PsycINFO, Scopus, Cochrane CENTRAL, CINAHL and ERIC from 2004 to 2014. Reviews were included if the authors indicated a systematic approach in their literature searches, and if they comprised interventions in Westernized countries targeting the general population. We identified 39 reviews that met the inclusion criteria. Mental health intervention approaches and outcomes varied across age groups and settings, and included functional, social, and cognitive measures. Most interventions aimed to prevent a specific mental illness or symptoms (depression, anxiety, burnout, or stress). Cognitive-behavioral therapy and educational components were common. School-based programs focused on outcomes involving social and academic development. Interventions for families, especially for young or disadvantaged parents, taught parenting skills to help improve the well-being of children and their care-givers. In the workplace, the focus was on managing stress, while programs for the elderly emphasized quality of life determinants. This review summarizes a wide variety of interventions to promote mental health or prevent mental illness, but the literature is primarily focused on the individual or family unit. More information is required about interventions at the community and societal levels. PMID- 26896635 TI - Algal toxin profiles in Nigerian coastal waters (Gulf of Guinea) using passive sampling and liquid chromatography coupled to mass spectrometry. AB - Algal toxins may accumulate in fish and shellfish and thus cause poisoning in consumers of seafood. Such toxins and the algae producing them are regularly surveyed in many countries, including Europe, North America, Japan and others. However, very little is known regards the occurrence of such algae and their toxins in most African countries. This paper reports on a survey of phytoplankton and algal toxins in Nigerian coastal waters. Seawater samples were obtained from four sites for phytoplankton identification, on three occasions between the middle of October 2014 and the end of February 2015 (Bar Beach and Lekki in Lagos State, Port Harcourt in Rivers State and Uyo in Akwa Ibom State). The phytoplankton community was generally dominated by diatoms and cyanobacteria; however several species of dinoflagellates were also identified: Dinophysis caudata, Lingulodinium polyedrum and two benthic species of Prorocentrum. Passive samplers (containing Diaion((r)) HP-20 resin) were deployed for several 1-week periods on the same four sites to obtain profiles of algal toxins present in the seawater. Quantifiable amounts of okadaic acid (OA) and pectenotoxin 2 (PTX2), as well as traces of dinophysistoxin 1 (DTX1) were detected at several sites. Highest concentrations (60 ng OA g(-1) HP-20 resin) were found at Lekki and Bar Beach stations, which also had the highest salinities. Non-targeted analysis using full-scan high resolution mass spectrometry showed that algal metabolites differed from site to site and for different sampling occasions. Screening against a marine natural products database indicated the potential presence of cyanobacterial compounds in the water column, which was also consistent with phytoplankton analysis. During this study, the occurrence of the marine dinoflagellate toxins OA and PTX2 has been demonstrated in coastal waters of Nigeria, despite unfavourable environmental conditions, with regards to the low salinities measured. Hence shellfish samples should be monitored in future to assess the risk for public health through accumulation of such toxins in seafood. PMID- 26896637 TI - Prognostic role of 25-hydroxyvitamin D in patients with liver metastases from colorectal cancer treated with radiofrequency ablation. AB - BACKGROUND AND AIM: Vitamin D is implicated in the etiology of several neoplastic diseases, but its relationship with colorectal cancer survival is still unclear. Aim of this study was to determine whether vitamin D levels influence survival outcomes in colorectal cancer liver metastases patients treated with percutaneous radiofrequency ablation. METHODS: We measured 25-hydroxyvitamin D levels in 143 patients with 215 colorectal liver metastases who underwent radiofrequency ablation between 1999 and 2011 at our institution. The influence of 25 hydroxyvitamin D levels on overall survival and time to recurrence was evaluated in univariate and multivariate Cox analyses. RESULTS: Median age was 68 years (range 41-85), and median number of nodules was 2 (1-3) with a median maximum diameter of 26 mm (10-48). Median survival was 44 months (36-62), and survival rate was 91.4%, 46.5%, and 42.2% at 1, 4, and 5 years in the whole cohort. Median survival was 65 months (52-74) if 25-hydroxyvitamin D >20 ng/mL and 34 months (24 41) if <=20 ng/mL (P < 0.001). In the whole cohort, median time to recurrence was 34 months (26-47), 50 months (36-62) in the case of 25-hydroxyvitamin D >20 ng/mL and 24 months (20-32) if <=20 ng/mL (P < 0.001). Nodule size and 25 hydroxyvitamin D resulted as significant predictors of both overall survival and time to recurrence in multivariate analysis. CONCLUSIONS: Our study provides support for the use of 25-hydroxyvitamin D as a new predictor of outcome for colorectal liver metastases patients. PMID- 26896638 TI - Psychological factors influence the overlap syndrome in functional gastrointestinal disorders and their effect on quality of life among firefighters in South Korea. AB - OBJECTIVE: The aim of this study was to investigate the predictor variables that could influence overlap syndrome in functional gastrointestinal disorders (FGID) among firefighters in Korea. METHODS: Data collected from 1217 firefighters in Korea were reviewed. FGID were diagnosed according to the Rome III diagnostic criteria. Psychological factors were measured by self-reported questionnaires. The scores for depression, anxiety, quality of life (QOL) and occupational job stress were analyzed. The correlation between psychological factors and QOL was analyzed and a stepwise multiple regression analysis was performed. RESULTS: FGID were observed in 461 (37.9%) participants. In those with FGID, functional heartburn (FH) was most common (32.2%), followed by functional dyspepsia (12.2%). Patients with overlap syndrome had the highest depression, anxiety and occupational stress score than those having non-overlap syndrome and healthy controls, respectively (depression: F = 142.29, eta(2) = 0.190; anxiety: F = 88.33, eta(2) = 0.127; occupational stress: F = 43.68, eta(2) = 0.067; all P < 0.001). Healthy controls had the highest QOL score (F = 73.39, P < 0.001, eta(2) = 0.108). Pychological factors were significantly correlated with QOL in the overlap syndrome of FGID. After the stepwise selection, the final model explained 45.6% of predictable variance and contained four significant variables: depression, self-esteem, occupational stress and anxiety. CONCLUSIONS: Psychological factors are associated with the overlap syndrome of FGID. Acknowledging this common comorbidity may facilitate the recognition and treatment of patients with FGID. PMID- 26896640 TI - Addison's disease with polyglandular autoimmunity carries a more than 2.5-fold risk for adrenal crises: German Health insurance data 2010-2013. AB - OBJECTIVE: Adrenal crises are potentially life-threatening complications in patients with adrenal insufficiency (AI). Our objective was to investigate the frequency of adrenal crises in different forms of AI. DESIGN/PATIENTS: The Statutory Health Insurance (SHI) database of the Techniker Krankenkasse - covering more than 12% of the German population - was analysed for diagnostic codes from 1 January 2010 to 31 December 2013. MEASUREMENTS: By analysis of routine data from a large healthcare provider. Diagnoses of AI were recorded and classified in primary AI, secondary AI and autoimmune polyglandular syndrome (APS). The ICD-code E27.2 (AC) was retrieved in all cohorts. RESULTS: We found a prevalence of 222/million for secondary and 126/million for primary AI. AC was documented with a frequency of 4.8/100 patient years. Crises were significantly more frequent in patients with primary (7.6/100 patient years) compared to those with secondary AI (3.2/100 patient years; P < 0.0001). Prevalence of crises was higher in individuals with APS (10.9/100 patient years) and highest in patients with primary AI and type 1 diabetes (12.5/100 patient years). CONCLUSIONS: Applying a SHI database comprising more than 9 million individuals, we identified robust data about the risk of AC in different groups of patients with AI. Our data confirm and extend the clinical observation that patients with APS are at highest risk for AC. Approximately 1 of 8 patients with primary AI and type 1 diabetes suffers from an AC each year. Specific targeting of efforts aiming at the prevention of AC is necessary. PMID- 26896639 TI - Validation of alternative capillary electrophoresis detection of STRs using POP-6 polymer and a 22cm array on a 3130xl genetic analyzer. AB - The goal of this project was to reduce capillary electrophoresis detection time on a 3130xl Genetic Analyzer for amplification product obtained from 4-dye and 5 dye STR amplification kits while still generating high quality STR profiles. This was accomplished by utilizing a more viscous polymer (POP-6TM) and a shorter array (22 cm) than that which are typically used (POP-4((r)) polymer and a 36 cm array) for human identification purposes. Spatial calibration and detection run modules were modified in response to the use of this polymer/array combination and to reduce detection time. Alternative detection resulted in 24-28 min run times, as compared to ~45 min using traditional POP-4((r))/36 cm detection methods. POP-6TM/22 cm detection run modules were validated for use with 4-dye Promega STR kits (e.g., PowerPlex((r)) 16 and PowerPlex((r)) 16HS) and 5-dye Life Technologies kits (e.g., Identifiler((r)) and Identifiler((r)) Plus). Three hundred ninety-five samples, controls and allelic ladders were used for the validation studies, which consisted of a comparison of alternative POP-6TM/22 cm detection to traditional POP-4((r))/36 cm (including reproducibility/concordance of allele calls, resolution, ILS sizing quality, peak height and pass rates), a sizing study (precision and accuracy) and a sensitivity study to obtain a usable range of injection times. Compared to traditional POP-4((r))/36 cm detection, alternative detection resulted in 100% reproducible and concordant alleles, the ability to achieve one base resolution, slightly reduced ILS sizing quality, slightly reduced peak height and statistically similar pass rates (alpha=0.05). It should be noted that alternative detection offered improved resolution over that of traditional for amplicons less than ~200 b, but had reduced resolution for products greater than ~200 b. Additionally, alternative detection yielded acceptable precision and accuracy of sizing using Life Technologies criteria (<0.15 standard deviation of allele sizing and +/-0.5b sizing differences for the same allele) and usable injection parameters of 2 kV 4-15s (compared to 3 kV 10s for traditional). The run modules developed and validated for 4-dye and 5-dye STR kits using POP-6TM polymer on a 22 cm array offer a tremendous reduction in detection time (~40%) while still generating high quality STR profiles. PMID- 26896641 TI - A comparative analysis of different molecular targets using PCR for diagnosis of old world leishmaniasis. AB - The different sensitivity values were obtained in each study conducted for the diagnosis of leishmaniasis with the polymerase chain reaction (PCR). However, a standardized PCR target for the diagnosis of leishmaniasis does not exist. The aim of the current study, the most ideal PCR target was determined for diagnosis of leishmaniasis. A total of 72 smear and 48 bone marrow samples were analyzed with six different molecular targets to determine their potential as a tool for the specific molecular diagnosis of leishmaniasis using PCR. The positivity negativity value and the sensitivity-specificity of each PCR targets were calculated. The positivity value of PCR targets were sequenced in different levels in the diagnosis of leishmaniasis from highest to lowest in the order of kDNA-PCR > SSU rRNA-PCR > ITS2-PCR > ITS1-PCR > ME-PCR > HSP70-PCR. The sensitivities of PCR targets except ITS1-PCR, ME-PCR and HSP70-PCR were found to be 100% in cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL) cases as compared to microscopic examination accepted as a gold standard. The sensitivities of ITS1-PCR, ME-PCR and HSP70-PCR were found 96.6%, 90.0% and 86.6%, respectively, in CL-cases. In addition, the sensitivities of ITS1-PCR, ME PCR and HSP70-PCR were found 90.0%, 70.0% and 60.0%, respectively, in VL-cases. The kDNA genomic region was the most sensitive for routine diagnosis of leishmaniasis. ITS1-PCR restriction fragment length polymorphism, the alternative method for the identification of Old World Leishmania species, did not require culturing of the parasites. PMID- 26896642 TI - Role of the 52 KDa thioredoxin protein disulfide isomerase of Toxoplasma gondii during infection to human cells. AB - Toxoplasma protein disulfide isomerase (PDI) is a 52 KDa thioredoxin of interest because have a great immunogenicity for humans. We cloned and produced a recombinant protein (recTgPDI) used to test its effect during infection to different human cell lines (epithelial and retinal). We also determine if there were differences in gen expression during in vitro infection. Expression of the gen was lower after entry into the host cells. PDI's inhibitors bacitracin and nitroblue tetrazolium reduced the percent of infected cells and small amounts of recTgPDI proteins interfered with the invasion step. All these results support a role of Toxoplasma PDI during the first steps of infection (adhesion and invasion). Toxoplasma PDI is a protein linked to early steps of invasion, it would be of importance to identify the host proteins substrates during invasion steps. PMID- 26896644 TI - How Can the Complications of Central Vein Catheters Be Reduced?: Preventing Common Complications of Central Vein Catheters. PMID- 26896643 TI - Tuberculosis verrucosa cutis lesions exhibit a greater microvessel count than lupus vulgaris lesions. PMID- 26896645 TI - Submicron-surface structured tricalcium phosphate ceramic enhances the bone regeneration in canine spine environment. AB - Calcium phosphate ceramics with submicron-scaled surface structure can trigger bone formation in non-osseous sites and are expected to enhance bone formation in spine environment. In this study, two tricalcium phosphate ceramics having either a submicron-scaled surface structure (TCP-S) or a micron-scaled one (TCP-B) were prepared and characterized regarding their physicochemical properties. Granules (size 1-2 mm) of both materials were implanted on either left or right side of spinous process, between the two lumbar vertebrae (L3-L4), and in paraspinal muscle of eight beagles. After 12 weeks of implantation, ectopic bone was observed in muscle in TCP-S explants (7.7 +/- 3.7%), confirming their ability to inductively form bone in non-osseous sites. In contrast, TCP-B implants did not lead to bone formation in muscle. Abundant bone (34.1 +/- 6.6%) was formed within TCP-S implants beside the two spinous processes, while limited bone (5.1 +/- 4.5%) was seen in TCP-B. Furthermore, the material resorption of TCP-S was more pronounced than that of TCP-B in both the muscle and spine environments. The results herein indicate that the submicron-scaled surface structured tricalcium phosphate ceramic could enhance bone regeneration as compared to the micron scaled one in spine environment. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1865-1873, 2016. PMID- 26896646 TI - Bioavailable inhibitors of HIV-1 RNA biogenesis identified through a Rev-based screen. AB - New antiretroviral agents with alternative mechanisms are needed to complement the combination therapies used to treat HIV-1 infections. Here we report the identification of bioavailable molecules that interfere with the gene expression processes of HIV-1. The compounds were detected by screening a small library of FDA-approved drugs with an assay based on measuring the displacement of Rev, and essential virus-encoded protein, from its high-affinity RNA binding site. The antiretroviral activity of two hits was based on interference with post integration steps of the HIV-1 cycle. Both hits inhibited RRE-Rev complex formation in vitro, and blocked LTR-dependent gene expression and viral transcription in cellular assays. The best compound altered the splicing pattern of HIV-1 transcripts in a manner consistent with Rev inhibition. This mechanism of action is different from those used by current antiretroviral agents. The screening hits recognized the Rev binding site in the viral RNA, and the best compound did so with substantial selectivity, allowing the identification of a new RNA-binding scaffold. These results may be used for developing novel antiretroviral drugs. PMID- 26896647 TI - Hypoxia-driven glycolytic and fructolytic metabolic programs: Pivotal to hypertrophic heart disease. AB - Pathologic cardiac growth is an adaptive response of the myocardium to various forms of systemic (e.g. pressure overload) or genetically-based (e. g. mutations in genes encoding sarcomeric proteins) stress. It represents a key aspect of different types of heart disease including aortic stenosis (AS) and hypertrophic cardiomyopathy (HCM). While many of the pathophysiological and hemodynamical aspects of pathologic cardiac hypertrophy have been uncovered during the last decades, its underlying metabolic determinants are only beginning to come into focus. Here, we review the epidemiological evidence and pathological features of hypertrophic heart disease in AS and HCM and consider in this context the development of microenvironmental tissue hypoxia as a key component of the heart's growth response to pathologic stress. We particularly reflect on recent evidence illustrating how activation of hypoxia-inducible factor (HIF) drives glycolytic and fructolytic metabolic programs to maintain ATP generation and support anabolic growth of the pathologically-stressed heart. Finally we discuss how this metabolic programs, when protracted, deprive the heart of energy leading ultimately to heart failure. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel. PMID- 26896648 TI - Chronic alcohol binging injures the liver and other organs by reducing NAD+ levels required for sirtuin's deacetylase activity. AB - NAD(+) levels are markedly reduced when blood alcohol levels are high during binge drinking. This causes liver injury to occur because the enzymes that require NAD(+) as a cofactor such as the sirtuin de-acetylases cannot de acetylate acetylated proteins such as acetylated histones. This prevents the epigenetic changes that regulate metabolic processes and which prevent organ injury such as fatty liver in response to alcohol abuse. Hyper acetylation of numerous regulatory proteins develops. Systemic multi-organ injury occurs when NAD(+) is reduced. For instance the Circadian clock is altered if NAD(+) is not available. Cell cycle arrest occurs due to up regulation of cell cycle inhibitors leading to DNA damage, mutations, apoptosis and tumorigenesis. NAD(+) is linked to aging in the regulation of telomere stability. NAD(+) is required for mitochondrial renewal. Alcohol dehydrogenase is present in every visceral organ in the body so that there is a systemic reduction of NAD(+) levels in all of these organs during binge drinking. PMID- 26896650 TI - Increased expression of Toll-like receptors 3, 7, 8 and 9 in peripheral blood mononuclear cells in patients with psoriasis. PMID- 26896649 TI - Over-expression of survivin is a factor responsible for differential responses of ovarian cancer cells to S-allylmercaptocysteine (SAMC). AB - While investigating the inhibitory effect of S-allylmercaptocysteine (SAMC), a garlic derivative, on ovarian cancer, we subjected three ovarian cancer cell lines, HO8910, HO8910PM, and SKOV3, to SAMC treatment. In vivo and in vitro experiments showed that only HO8910 and SKOV3 cells were highly sensitive to SAMC, whereas HO8910PM cells were resistant to SAMC. Subsequently, we examined the apoptosis-related genes in the three cell lines. We found that survivin gene was highly expressed in HO8910PM cells. Down regulation of survivin gene in HO8910PM cells with small interference RNA (siRNA), resulted in increased sensitivity to SAMC together with a decrease in invasiveness of tumor cells. We therefore concluded that the S-allylmercaptocysteine suppresses both the proliferation and distant metastasis of epithelial ovarian cancer cells, insensitivity of HO8910PM cells to SAMC was closely related to the high level of survivin expression and that combination of SAMC treatment together with survivin knockdown might be a potential strategy for treatment of certain variants of ovarian cancers. PMID- 26896651 TI - Harnessing steric hindrance to control interfacial adsorption of patchy nanoparticles onto hairy vesicles. AB - Via the Dissipative Particle Dynamics simulation technique we investigate the interfacial adsorption of nanoparticles with a binding site onto a hairy vesicle encompassing phospholipids and lipids functionalized with oligo ethylene glycol (OEG) chain. The functionalized nanoparticles are modeled as patchy spherical particles. We examine the relation between the relative concentration and size of the OEG chains, the adsorption kinetics, life-time and post-adsorption dynamics of the nanoparticles. We also draw correspondence with experimental studies on the adsorption of proteins onto the surface of colloidal particles. Results from our investigations can elucidate the fundamental factors and mechanisms controlling the adsorption of functionalized nanoparticles onto colloidal particles. PMID- 26896652 TI - Magnetite nanocluster@poly(dopamine)-PEG@ indocyanine green nanobead with magnetic field-targeting enhanced MR imaging and photothermal therapy in vivo. AB - Multifunctional nanomaterials with the magnetic resonance imaging (MRI) guided tumor photothermal ablation ability have been extensively applied in biomedical research as one of the most exciting and challenging strategies for cancer treatment. Nevertheless, most of these nanomaterials still suffer from low accumulation in tumor tissues and insufficient photothermal ablation of tumors so far. Here, we report a novel approach to overcome these limitations using a core shell magnetite nanocluster@poly(dopamine)-PEG@ICG nanobead compositing of magnetite nanocluster core with coating of poly(dopamine), then further conjugating with polyethylene glycol (PEG) and adsorbing indocyanine green (ICG) on the surface. The adsorbed ICG in the nanobead displays a higher photostability and photothermal conversion ability than free ICG, as well as additional photothermal effect rather than magnetite nanocluster and poly(dopamine), which endow the nanobead with enhanced photothermal killing efficiency against cancer cells under near-infrared (NIR) laser irritation. Furthermore, it is proved that these nanobeads have excellent biocompatibility, T2-weighted MR imaging and magnetic field targeting ability. By applying an external magnetic field (MF) focused on the targeted tumor, a magnetic targeting mediated enhanced accumulation is observed at tumor site as proved by a darker T2-weighted MR image. Utilizing the magnetic targeting strategy, enhanced photothermal tumor ablation was achieved under laser irradiation in vivo, which is reflected by the degree of tumor tissue damage and tumor growth delay. Therefore, this nanobead integrates the abilities of magnetic field-targeting, MR imaging and photothermal cancer therapy, and might be a promising theranostic platform for tumor treatment. PMID- 26896653 TI - Enhancing in vitro dissolution and in vivo bioavailability of fenofibrate by solid self-emulsifying matrix combined with SBA-15 mesoporous silica. AB - Mesoporous silica Santa Barbara amorphous-15 (SBA-15), derived from supermolecular assemblies of surfactant Pluronic((r)) P123 with well-ordered 2-D hexagonal pores, was investigated as a reservoir to construct a novel solid self emulsifying matrix for enhancing the oral bioavailability of fenofibrate (FNB). The emulsification rate and droplet size of a liquid self-emulsifying delivery system (SEDDS) were analyzed for optimization. SBA-15 was then added to the ethanol solution containing liquid SEDDS, and the obtained suspension changed into solid SEDDS matrix via solvent evaporation. The characterizations by SEM and XRD revealed that the solid matrix consisted of particles with smooth surface and FNB was completely transformed into molecular or amorphous state in the formulation. When introduced to aqueous media under gentle agitation, the solid matrix exhibited excellent self-emulsification properties and formed a uniform microemulsion with mean diameter of 117.35 +/- 2.33 nm. The solid SEDDS matrix showed faster in vitro release rate than the raw powder and commercial capsule. The absorption of FNB delivered by solid SEDDS matrix was significantly improved in beagle dogs, and its Cmax and AUC values were about 8- and 4-fold greater than those of commercial products, respectively. In conclusion, SBA-15 emerged as a promising reservoir for SEDDS to enhance the bioavailability of poorly water soluble drugs, which may provide a new strategy for advanced therapies. PMID- 26896654 TI - Development of antibacterial and high light transmittance bulk materials: Incorporation and sustained release of hydrophobic or hydrophilic antibiotics. AB - Infection associated with medical devices is one of the most frequent complications of modern medical biomaterials. Bacteria have a strong ability to attach on solid surfaces, forming colonies and subsequently biofilms. In this work, a novel antibacterial bulk material was prepared through combining poly(dimethyl siloxane) (PDMS) with either hydrophobic or hydrophilic antibiotics (0.1-0.2 wt%). Scanning electron microscopy, water contact angle and UV-vis spectrophotometer were used to measure the changes of surface topography, wettability and optical transmission. For both gentamicin sulfate (GS) and triclosan (TCA), the optical transmission of the PDMS-GS and PDMS-TCA blend films was higher than 90%. Drug release studies showed initial rapid release and later sustained release of GS or TCA under aqueous physiological conditions. The blend films demonstrated excellent bactericidal and sufficient biofilm inhibition functions against Gram-positive bacteria (Staphylococcus aureus, S. aureus) measured by LIVE/DEAD bacterial viability kit staining method. Kirby-Bauer method showed that there was obvious zone of inhibition (7.5-12.5mm). Cytocompatibility assessment against human lens epithelial cells (HLECs) revealed that the PDMS-GS blend films had good cytocompatibility. However, the PDMS-TCA blend films showed certain cytotoxicity against HLECs. The PDMS-0.2 wt% GS blend films were compared to native PDMS in the rabbit subcutaneous S. aureus infection model. The blend films yielded a significantly lower degree of infection than native PDMS at day 7. The achievement of the PDMS-drug bulk materials with high light transmittance, excellent bactericidal function and good cytocompatibility can potentially be widely used as bio-optical materials. PMID- 26896655 TI - Osteogenic effect of controlled released rhBMP-2 in 3D printed porous hydroxyapatite scaffold. AB - Recently, 3D printing as effective technology has been highlighted in the biomedical field. Previously, a porous hydroxyapatite (HA) scaffold with the biocompatibility and osteoconductivity has been developed by this method. However, its osteoinductivity is limited. The main purpose of this study was to improve it by the introduction of recombinant human bone morphogenetic protein-2 (rhBMP-2). This scaffold was developed by coating rhBMP-2-delivery microspheres with collagen. These synthesized scaffolds were characterized by Scanning Electron Microscopy (SEM), a delivery test in vitro, cell culture, and the experiments in vivo by a Micro-computed tomography (MUCT) scan and histological evaluation of VanGieson staining. SEM results indicated the surface of scaffolds were more fit for the adhesion of hMSCs to coat collagen/rhBMP-2 microspheres. Biphasic release of rhBMP-2 could continue for more than 21 days, and keep its osteoinductivity to induce osteogenic differentiation of hMSCs in vitro. In addition, the experiments in vivo showed that the scaffold had a good bone regeneration capacity. These findings demonstrate that the HA/Collagen/Chitosan Microspheres system can simultaneously achieve localized long-term controlled release of rhBMP-2 and bone regeneration, which provides a promising route for improving the treatment of bone defects. PMID- 26896656 TI - Hyaluronan/chitosan nanofilms assembled layer-by-layer and their antibacterial effect: A study using Staphylococcus aureus and Pseudomonas aeruginosa. AB - In the last few years, chitosan-based coatings have been proposed as antibacterial surfaces for biomedical devices in order to prevent nosocomial infections. In that sense, this work reports the optimized synthesis of hyaluronan/chitosan (HA/CHI) nanofilms assembled layer-by-layer in order to maximize the antibacterial effect for two important human pathogenic bacteria, Staphylococcus aureus and Pseudomonas aeruginosa. In this assembly, HA forms a soft, highly hydrated, and nontoxic film, whereas CHI shows the antimicrobial characteristics. Our HA/CHI nanofilm synthesis optimization was based on changing pH values of the biopolymer stem-solutions and the consequent variation of their ionization degree. Furthermore, the surface density of primary amino groups, which are related to the antibacterial effect, was also enhanced by increasing the number of HA/CHI bilayers. The antibacterial effect of HA/CHI nanofilms was evaluated by the spread plate counting method for both bacteria. These results were correlated with the morphology of nanofilms (characterized using SEM and AFM), as well as with their chemical properties studied by UV-vis, Kelvin Probe Force microscopy and XPS spectroscopy. PMID- 26896657 TI - Preparation of a thick polymer brush layer composed of poly(2 methacryloyloxyethyl phosphorylcholine) by surface-initiated atom transfer radical polymerization and analysis of protein adsorption resistance. AB - The purpose of this study was to prepare a thick polymer brush layer composed of poly(2-methacryloyloxyethyl phosphorylcholine (MPC)) and assess its resistance to protein adsorption from the dissolved state of poly(MPC) chains in an aqueous condition. The thick poly(MPC) brush layer was prepared through the surface initiated atom transfer radical polymerization (SI-ATRP) of MPC with a free initiator from an initiator-immobilized substrate at given [Monomer]/[Free initiator] ratios. The ellipsometric thickness of the poly(MPC) brush layers could be controlled by the polymerization degree of the poly(MPC) chains. The thickness of the poly(MPC) brush layer in an aqueous medium was larger than that in air, and this tendency became clearer when the polymerization degree of the poly(MPC) increased. The maximum thickness of the poly(MPC) brush layer in an aqueous medium was around 110 nm. The static air contact angle of the poly(MPC) brush layer in water indicated a reasonably hydrophilic nature, which was independent of the thickness of the poly(MPC) brush layer at the surface. This result occurred because the hydrated state of the poly(MPC) chains is not influenced by the environment surrounding them. Finally, as measured with a quartz crystal microbalance, the amount of protein adsorbed from a fetal bovine serum solution (10% in phosphate-buffered saline) on the original substrate was 420 ng/cm(2). However, the poly(MPC) brush layer reduced this value dramatically to less than 50 ng/cm(2). This effect was independent of the thickness of the poly(MPC) brush layer for thicknesses between 20 nm and about 110 nm. These results indicated that the surface covered with a poly(MPC) brush layer is a promising platform to avoid biofouling and could also be applied to analyze the reactions of biological molecules with a high signal/noise ratio. PMID- 26896658 TI - Study of the conformational change of adsorbed proteins on biomaterial surfaces using hydrogen-deuterium exchange with mass spectroscopy. AB - There is no doubt that protein adsorption plays a crucial role in determining biocompatibility of biomaterials. Despite the information of the identity and composition of blood plasma/serum proteins adsorbed on surfaces of biomaterials to understand which proteins are involved in blood/biomaterial interactions, it still does not provide information about the conformations and orientations of adsorbed protein, which are very important in determining biological responses to biomaterials. Therefore, our laboratory has developed an experimental technology to probe protein conformations on materials that is applicable to mixtures of proteins. Herein, the new application of hydrogen/deuterium (H/D) exchange combined with mass spectrometry was applied to determine conformational changes of adsorbed proteins at biomaterial surfaces. The results suggest that there may be a significant conformational change in adsorbed proteins at 'low' bulk concentrations that leads to a large change in the kinetics of H/D exchange as compared to 'high' bulk concentrations. This technique may eventually be useful for the study of the kinetics of protein conformational changes. PMID- 26896659 TI - Controlled superficial assembly of DNA-amorphous calcium phosphate nanocomposite spheres for surface-mediated gene delivery. AB - Surface-mediated gene delivery systems have many potential applications in tissue engineering. We recently fabricated an assembly consisting of DNA-amorphous calcium phosphate (DNA-ACP) nanocomposite spheres on a polymer substrate via coprecipitation in a labile supersaturated calcium phosphate (CaP) solution and demonstrated the assembly's high gene delivery efficacy. In this study, we conducted a detailed investigation of the coprecipitation process in solution and revealed that the negatively charged DNA molecules were immobilized in the ACP spheres during the initial stage of coprecipitation and functioned as both sphere dispersing and size-regulating agents. As a result, the DNA-ACP nanocomposites grew into size-regulated submicrospheres in solution and assembled onto the substrate via gravity sedimentation. The assembled nanocomposite spheres were chemically anchored to the substrate surface through an intermediate layer of CaP based nanoparticles that was formed heterogeneously at the substrate surface. The coprecipitation conditions, i.e., coprecipitation time and Ca and P concentrations in solution, greatly affected the state of assembly of the nanocomposite spheres, thereby influencing the gene expression level of the cells cultured on the substrate. Increasing the number density and decreasing the size of the nanocomposite spheres did not always increase the assembly's gene delivery efficacy (per surface area of the substrate) due to adverse effects on cellular viability. As demonstrated herein, controlling the coprecipitation conditions is important for designing a cell-stimulating and biocompatible scaffold surface consisting of an assembly of DNA-ACP nanocomposite spheres. PMID- 26896660 TI - Role of amphipathicity and hydrophobicity in the balance between hemolysis and peptide-membrane interactions of three related antimicrobial peptides. AB - Cationic antimicrobial peptides (CAMPs) represent important self defense molecules in many organisms, including humans. These peptides have a broad spectrum of activities, killing or neutralizing many Gram-negative and Gram positive bacteria. The emergence of multidrug resistant microbes has stimulated research on the development of alternative antibiotics. In the search for new antibiotics, cationic antimicrobial peptides (CAMPs) offer a viable alternative to conventional antibiotics, as they physically disrupt the bacterial membranes, leading to lysis of microbial membranes and eventually cell death. In particular, the group of linear alpha-helical cationic peptides has attracted increasing interest from clinical as well as basic research during the last decade. In this work, we studied the biophysical and microbiological characteristics of three new designed CAMPs. We modified a previously studied CAMP sequence, in order to increase or diminish the hydrophobic face, changing the position of two lysines or replacing three leucines, respectively. These mutations modified the hydrophobic moment of the resulting peptides and allowed us to study the importance of this parameter in the membrane interactions of the peptides. The structural properties of the peptides were also correlated with their membrane disruptive abilities, antimicrobial activities and hemolysis of human red blood cells. PMID- 26896661 TI - Biopanning and characterization of peptides with Fe3O4 nanoparticles-binding capability via phage display random peptide library technique. AB - Functionalization of inorganic nanoparticles (NPs) play an important role in biomedical applications. A proper functionalization of NPs can improve biocompatibility, avoid a loss of bioactivity, and further endow NPs with unique performances. Modification with vairous specific binding biomolecules from random biological libraries has been explored. In this work, two 7-mer peptides with sequences of HYIDFRW and TVNFKLY were selected from a phage display random peptide library by using ferromagnetic NPs as targets, and were verified to display strong binding affinity to Fe3O4 NPs. Fourier transform infrared spectrometry, fluorescence microscopy, thermal analysis and X-ray photoelectron spectroscopy confirmed the presence of peptides on the surface of Fe3O4 NPs. Sequence analyses revealed that the probable binding mechanism between the peptide and Fe3O4 NPs might be driven by Pearson hard acid-hard base specific interaction and hydrogen bonds, accompanied with hydrophilic interactions and non specific electrostatic attractions. The cell viability assay indicated a good cytocompatibility of peptide-bound Fe3O4 NPs. Furthermore, TVNFKLY peptide and an ovarian tumor cell A2780 specific binding peptide (QQTNWSL) were conjugated to afford a liner 14-mer peptide (QQTNWSLTVNFKLY). The binding and targeting studies showed that 14-mer peptide was able to retain both the strong binding ability to Fe3O4 NPs and the specific binding ability to A2780 cells. The results suggested that the Fe3O4-binding peptides would be of great potential in the functionalization of Fe3O4 NPs for the tumor-targeted drug delivery and magnetic hyperthermia. PMID- 26896662 TI - Nanosized Fe3O4 an efficient PCR yield enhancer-Comparative study with Au, Ag nanoparticles. AB - Nanomaterials-assisted PCR is a promising field of nanobiotechnology that amalgamates nanomaterials into the conventional PCR system to achieve better amplification of desired product. With literature documenting the variable effects of these nanomaterials on the PCR yield and amplification; it was thought worthwhile to compare the PCR enhancing efficiency of three transition metal nanoparticles in form of stable colloidal suspensions at varying concentrations.The nanoparticles(NPs) of silver, gold and magnetite were chemically synthesized by reducing their respective salts and characterized using UV-vis spectroscopy. Their morphology was assessed using nanoparticle tracking system and AFM. The effect of these nanofluids on amplification of 800 bp prokaryotic DNA template with 30% GC content was studied using conventional thermal cycler. The reaction kinetics for all the three nanofluids yielded a Gaussian curve of amplification with varying concentrations. The ammonium salt of oleic acid coated magnetite (Fe3O4) nanoparticles at a concentration of 0.72 * 10(-2)nM and average size of 33 nm demonstrated highest amplification efficiency of 190% as compared to the citrate stabilized AgNP-25 nm (45%) and AuNP-15.19 nm (134%) using a conventional PCR system. The major reasons that allow Fe3O4 NPs outperform the other 2 transition metal NP's seem to be attributed to its heat conduction property as well as effective adsorption of PCR components onto the ammonium salt of oleic acid coated magnetite nanofluids. The data from our study offers valuable information for the application of ferrofluids as economically, efficient and effective alternative for nanomaterial-assisted PCR yield enhancers. PMID- 26896663 TI - Ionisation effects on the permeation of pharmaceutical compounds through silicone membrane. AB - Silicone membrane is frequently used as an in vitro skin mimic whereby experiments incorporate a range of buffered media which may vary in pH. As a consequence of such variability in pH there is a corresponding variability in the degree of ionisation which in turn, could influence permeation through the mainly hydrophobic-rich membrane structure. This study reports the effect of pH on the permeation of five model compounds (benzoic acid, benzotriazole, ibuprofen, ketoprofen and lidocaine). For the five compounds analysed, each at three distinct percentages of ionisation, it was found that the greater extent of permeation was always for the more 'neutral', i.e. more greatly unionised, species rather than the anionic or cationic species. These findings fit with the theory that the hydrophobic membrane encourages permeation of 'lipid-like' structures, i.e. the more unionised form of compounds. However, results obtained with an Inverse Gas Chromatography Surface Energy Analyser (iGC SEA) indicate the membrane surface to be an electron dense environment. In the knowledge that unionised forms of compounds permeate (rather than the charged species) this negatively charged surface was not anticipated, i.e. the basic membrane surface did not appear to affect permeation. PMID- 26896664 TI - Hepatobiliary and pancreatic: Comparison between Chinese herbal medicine and Western medicine-induced liver injury of 1985 patients. AB - BACKGROUND AND AIM: Chinese herbal medicine (CHM), as well as Western medicine (WM), is an important cause of drug-induced liver injury (DILI). However, the differences between CHM and WM as agents implicated in liver injury have rarely been reported. METHODS: Overall, 1985 (2.05%) DILI cases were retrospectively collected from the 96 857 patients hospitalized because of liver dysfunction in the 302 Military Hospital between January 2009 and January 2014. RESULTS: In all the enrolled patients with DILI, CHM was implicated in 563 cases (28.4%), while 870 cases (43.8%) were caused by WM and the remaining patients (27.8%) by the combination of WM and CHM. Polygonum multiflorum was the major implicated CHM. Compared with WM, the cases caused by CHM showed more female (51 vs 71%, P < 0.001) and positive rechallenge (6.1 vs 8.9%, P = 0.046), a much greater proportion of hepatocellular injury (62.2 vs 88.5%, P < 0.001), and a higher mortality (2.8 vs 4.8%, P = 0.042); however, no differences in the rates of chronic DILI and ALF were found (12.9 vs 12.4%, P = 0.807; 7.6 vs 7.6%, P = 0.971). Based on Roussel Uclaf Causality Assessment Method, 75.6% of cases caused by CHM were classified as probable and only 16.6% as highly probable, significantly different from WM (38.4 and 60.3%, all P < 0.001). CONCLUSIONS: The causal relationship between CHM and liver injury is much complex, and the clinical characteristics of DILI caused by CHM differ from those caused by WM. PMID- 26896665 TI - Parricide cases of adult offenders from Turkey: A descriptive study. AB - The aim of this study was to examine and compare similarities and differences among types of parricide committed by adult offenders. The forensic psychiatric evaluation reports of the 4th Specialization Board of the Council of Forensic Medicine from 2009 to 2011 in Turkey were screened retrospectively. One hundred thirty-five adult perpetrators of parricide (125 male, 10 female) were detected, 51.9% of whom committed patricide, 40% of whom matricide and 8.1% of the perpetrators committed double parricide. Most of the perpetrators used sharp instruments as the killing method. No mental disorders were detected in 58.5% of the perpetrators, while psychotic disorders were identified in 30.4% of the cases. This study supported the predominance of sharp instruments as the killing method and a preponderance of matricide among the offenders with psychotic disorders. Although psychotic disorders were the most commonly detected mental disorders in the parricide offenders, most of them did not suffer from mental disorders. PMID- 26896666 TI - Inheritance pattern of lip prints among Malay population: A pilot study. AB - We assessed the resemblance of lip print patterns between parents and biological offspring in families of 31 Malay students as well as the distribution of different types of lip print in the study group. Only a few studies have successfully established the inheritance pattern of lip prints. Such studies can be population specific and need to be conducted in various populations. No such study have been conducted in Malay population in Malaysia, according to our knowledge. Present study was carried out to ascertain whether there is any inherence pattern in lip prints and thereby to investigate the potential role of lip prints in personal identification. We found 58.06% resemblance of lip print patterns between the parents and their biological offspring in our study. The influence of heredity in lip print pattern is still a new concept and there is lack of concrete evidence. The data from our study shows that there is potential influence of inheritance in the lip print patterns among the family members. Further researches involving larger samples size are suggested to derive more reliable and accurate results. The most common lip print pattern among the study group is type I (29.84%) followed by type II (23.12%), type III (22.45%), type I' (13.44%), type IV (9.54%) and type V (1.61%). Racial variations in lip print patterns and their prevalence may serve as an aid in forensic identification and crime scene investigation. The results of this pilot study will help in establishing guidelines for future researches on lip print analysis in Malaysia. CONTEXT: Lip print patterns are unique and individualistic. However, there are some similarities in basic patterns of lip prints between family members which may be attributed to influence of inheritance. AIMS: 1. To determine the inheritance pattern of lip prints among Malay family members of the student. 2. To identify the distribution of different types of lip prints among Malay population. SETTINGS: and DESIGN: Observational pilot study. METHODS AND MATERIAL: Lip prints of 124 individuals from 31 families consisting of father, mother and two children were recorded and classified based on Tsuchihashi Classification (1974). STATISTICAL ANALYSIS USED: Statistical analysis was performed for resemblance pattern among family members (Karl-Pearson Correlation Coefficient) and inter-observer variability (Kappa test). RESULTS: 58.06% positive resemblance was found between parents and biological offspring. The highest lip print pattern in the study group was type I (29.84%) and the least was type V (1.61%). CONCLUSIONS: There is positive resemblance in lip print patterns among family members which may be attributed to influence of inheritance. However, further studies with larger sample sizes need to be conducted to confirm the results. Type I lip print was the most prevalent pattern among the study subjects. PMID- 26896667 TI - A novel role for RGMa in modulation of bone marrow-derived dendritic cells maturation induced by lipopolysaccharide. AB - Repulsive guidance molecule a (RGMa) is known to mediate immune responses and has been indicated to modulates T cell activation and autoimmune diseases by dendritic cells (DCs), which hints its significant function in the latter cells. The aim of our study, therefore, was to evaluate the function of RGMa in DC maturation. We found that small interfering RNA (siRNA) successfully silenced the expression of RGMa in DCs. Even after LPS stimulation, RGMa-silenced DCs displayed an immature morphology, characterized by small, round cells with a few cell processes and organelles, and many pinocytotic vesicles. In the presence of LPS, RGMa siRNA transfection markedly reduced levels of CD80, CD86, CD40, and MHC II expression, as well as the secretion of IL-12p70 and TNF-alpha. With LPS treatment, RGMa siRNA-transfected DCs also showed increased levels of IL-10 and endocytosis. Moreover, in the presence of LPS, RGMa siRNA-transfected DCs displayed a low ability to induce T cell proliferation and differentiation, compared with negative control (NTi)-transfected or control DCs (p<0.05 for both). We conclude that after LPS stimulation, RGMa siRNA-transfected DCs show immunoregulatory and tolerogenic characteristics, which provides new insights into the immune system. PMID- 26896668 TI - Pre-clinical toxicity and immunogenicity evaluation of a MUC1-MBP/BCG anti-tumor vaccine. AB - Mucin 1 (MUC1), as an oncogene, plays a key role in the progression and tumorigenesis of many human adenocarcinomas and is an attractive target in tumor immunotherapy. Our previous study showed that the MUC1-MBP/BCG anti-tumor vaccine induced a MUC1-specific Th1-dominant immune response, simulated MUC1-specific cytotoxic T lymphocyte killing activity, and could significantly inhibit MUC1 expression B16 cells' growth in mice. To help move the vaccine into a Phase I clinical trial, in the current study, a pre-clinical toxicity and immunogenicity evaluation of the vaccine was conducted. The evaluation was comprised of a single dose acute toxicity study in mice, repeat-dose chronic toxicity and immunogenicity studies in rats, and pilot toxicity and immunogenicity studies in cynomolgus monkeys. The results showed that treatment with the MUC1-MBP/BCG anti tumor vaccine did not cause any organ toxicity, except for arthritis or local nodules induced by BCG in several rats. Furthermore, the vaccine significantly increased the levels of IFN-gamma in rats, indicating that Th1 cells were activated. In addition, the results showed that the MUC1-MBP/BCG anti-tumor vaccine induced a MUC1-specific IgG antibody response both in rats and cynomolgus monkeys. Collectively, these data are beneficial to move the MUC1-MBP/BCG anti tumor vaccine into a Phase I clinical trial. PMID- 26896669 TI - Penguins as bioindicators of mercury contamination in the southern Indian Ocean: geographical and temporal trends. AB - Penguins have been recently identified as useful bioindicators of mercury (Hg) transfer to food webs in the Southern Ocean over different spatial and temporal scales. Here, feather Hg concentrations were measured in adults and chicks of all the seven penguin species breeding in the southern Indian Ocean, over a large latitudinal gradient spanning Antarctic, subantarctic and subtropical sites. Hg was also measured in feathers of museum specimens of penguins collected at the same sites in the 1950s and 1970s. Our aim was to evaluate geographical and historical variations in Hg transfer to penguins, while accounting for feeding habits by using the stable isotope technique (delta(13)C, habitat; delta(15)N, diet/trophic level). Adult feather Hg concentrations in contemporary individuals ranged from 0.7 +/- 0.2 to 5.9 +/- 1.9 MUg g(-1) dw in Adelie and gentoo penguins, respectively. Inter-specific differences in Hg accumulation were strong among both adults and chicks, and mainly linked to feeding habits. Overall, penguin species that feed in Antarctic waters had lower feather Hg concentrations than those that feed in subantarctic and subtropical waters, irrespective of age class and dietary group, suggesting different Hg incorporation into food webs depending on the water mass. While accounting for feeding habits, we detected different temporal variations in feather Hg concentrations depending on species. Notably, the subantarctic gentoo and macaroni penguins had higher Hg burdens in the contemporary rather than in the historical sample, despite similar or lower trophic levels, respectively. Whereas increases in Hg deposition have been recently documented in the Southern Hemisphere, future monitoring is highly needed to confirm or not this temporal trend in penguins, especially in the context of actual changing Hg emission patterns and global warming. PMID- 26896671 TI - Sagittal cut injury of the foot at workplace - A rare injury pattern and its management. AB - Extremity injuries to employees in an industrial setting are not an uncommon event in today's mechanised workspace. Cut injuries of the foot during handling of machines are common in the workplace and the management of such injuries depends upon various factors at the time of presentation. This case report describes a rare foot injury which has not previously been reported in the literature and describes its subsequent successful management. PMID- 26896670 TI - Histories of abuse predict stronger within-person covariation of ovarian steroids and mood symptoms in women with menstrually related mood disorder. AB - OBJECTIVE: Individual differences in sensitivity to cyclical changes in ovarian steroids estradiol (E2) and progesterone (P4) have been implicated in the pathophysiology of menstrually related mood disorder (MRMD). However, no prospective studies have investigated psychosocial risk factors for sensitivity to hormone effects on mood in MRMD. Using a repeated measures approach and multilevel models, we tested the hypothesis that a history of abuse provides a context in which within-person elevations of E2 and P4 prospectively predict daily symptoms. METHOD: 66 women with prospectively-confirmed MRMD recruited for a trial of oral contraceptives provided 1 month of baseline hormone and mood data prior to randomization. Lifetime physical and sexual abuse experiences were assessed. Across one cycle, women completed daily measures of symptoms and provided blood samples on 5 days across the menstrual cycle. Current E2 and P4 were centered within person (CWP) such that higher values represented cyclical elevations in hormones. RESULTS: Rates of physical (27%) and sexual (29%) abuse were high, consistent with previous work documenting a link between trauma and MRMD. In women with a history of physical abuse, cyclical increases in P4 predicted greater mood and interpersonal symptoms on the three days following that sample. In women with a history of sexual abuse, cyclical increases in E2 predicted greater anxiety symptoms on the three days following that sample. CONCLUSIONS: Results inform further inquiry into the role of severe life stressors and stress response systems in MRMD. We discuss areas for future research on the psychosocial and physiological pathways through which abuse may influence the link between hormones and symptoms. PMID- 26896673 TI - Interactions between Metopolophium festucae cerealium (Hemiptera: Aphididae) and Barley yellow dwarf virus (BYDV-PAV). AB - Interactions between an invasive aphid, Metopolophium festucae (Theobald) subsp. cerealium, and Barley yellow dwarf virus (BYDV-PAV) were studied under laboratory conditions. M. festucae cerealium is an economic pest of wheat and barley that has recently been found in high population densities in wheat in the Pacific Northwest of the United States. BYDV-PAV is the most prevalent and injurious species of BYDV worldwide and in the Pacific Northwest. Although M. festucae sensu stricto (Theobald 1917) has been reported previously as a vector of some BYDV isolates, there is no confirmed transmission of BYDV by M. festucae cerealium. Two experiments examined the ability of M. festucae cerealium to transmit BYDV-PAV. The first used single aphids caged to indicator plants of a BYDV-susceptible winter wheat cultivar and the second used multiple aphids on each test plant. M. festucae cerealium did not transmit BYDV-PAV in either experiment, whereas transmission by a known BYDV vector, Rhopalosiphum padi L., was consistently high (>= 93%). A third experiment compared the intrinsic growth rate, days until first reproduction and daily reproduction by M. festucae cerealium on sham-inoculated and BYDV-PAV-infected wheat, but detected no differences. The findings are reviewed in light published data on M. festucae species, BYDV transmission, and the potential pest status of this new invading aphid. PMID- 26896672 TI - Translocated in liposarcoma regulates the distribution and function of mammalian enabled, a modulator of actin dynamics. AB - Translocated in liposarcoma/fused in sarcoma (TLS/FUS) is an RNA-binding protein that regulates the splicing pattern of mRNA transcripts and is known to cause a type of familial amyotrophic lateral sclerosis (ALS). In the absence of TLS, Mammalian enabled (Mena), an actin-regulatory protein and a target of TLS, undergoes preferential alternative splicing. In the present study, we show that the ablation of TLS dysregulates the subcellular location and functions of Mena. When TLS knockout (KO) mouse embryonic fibroblasts (MEFs) were transfected with wild-type Mena, it no longer accumulated at focal adhesions and peripheral structures, whereas the localization of the alternatively spliced form was maintained. Additionally, the ability of Mena to suppress the motility of cells was lost in TLS KO MEFs. Moreover, Mena failed to promote neurite outgrowth in TLS KO primary neurons. Taken together, TLS is intimately involved in the local cytoskeletal dynamics surrounding Mena in both fibroblasts and neurons. The robust change in cytoskeletal dynamics, as indicated by the dysregulation of Mena in TLS KO cells, provides a new insight into the pathogenesis of certain types of ALS. PMID- 26896674 TI - Taiwanese Trichogramma of Asian Corn Borer: Morphology, ITS-2 rDNA Characterization, and Natural Wolbachia Infection. AB - Egg parasitoids of the genus Trichogramma are natural enemies of many lepidopteran borers in agricultural areas around the world. It is important to identify the correct species and ideally focus on endemic Trichogramma for pest control in particular crops. In this study, Trichogramma wasps were collected from parasitized eggs of Asian corn borer in Southwestern Taiwan. Three Trichogramma species, Trichogramma ostriniae Pang and Chen, Trichogramma chilonis Ishii, and T. sp. y, were identified based on morphology and the nucleotide sequence of the internal transcribed spacer 2 (ITS-2) region of rDNA. Although T. ostriniae and T. sp. y appear to be morphologically similar, ITS-2 identity between these two taxa is only 89%. Surprisingly, a commercially released Trichogramma colony thought to be T. chilonis possessed 99% identity (ITS-2) with the field T. sp. y individuals. This suggests past contamination leading to subsitution of the laboratory-reared T. chilonis colony by T. sp. y. Natural populations of all three Trichogramma species were found to be infected by a single Wolbachia strain which was identified using a wsp gene sequence. PMID- 26896676 TI - A continuum model of transcriptional bursting. AB - Transcription occurs in stochastic bursts. Early models based upon RNA hybridisation studies suggest bursting dynamics arise from alternating inactive and permissive states. Here we investigate bursting mechanism in live cells by quantitative imaging of actin gene transcription, combined with molecular genetics, stochastic simulation and probabilistic modelling. In contrast to early models, our data indicate a continuum of transcriptional states, with a slowly fluctuating initiation rate converting the gene between different levels of activity, interspersed with extended periods of inactivity. We place an upper limit of 40 s on the lifetime of fluctuations in elongation rate, with initiation rate variations persisting an order of magnitude longer. TATA mutations reduce the accessibility of high activity states, leaving the lifetime of on- and off states unchanged. A continuum or spectrum of gene states potentially enables a wide dynamic range for cell responses to stimuli. PMID- 26896677 TI - A multidisciplinary approach to the management of traumatic intrusion in immature permanent teeth. AB - Intrusion in a developing permanent tooth is an extremely complicated traumatic injury and is rarely seen in the permanent dentition. The damage caused by the trauma to the surrounding tooth structures results in a multitude of complications during the healing process. Careful repositioning of the intruded tooth by orthodontic means, revascularisation of the immature tooth to regain vitality, and periodontal treatment to provide the most acceptable aesthetic outcome are described in this case report. It outlines the treatment options to overcome the complications and variable outcomes. The present report emphasises the importance of a multidisciplinary approach to provide complete rehabilitation of a traumatically intruded developing tooth. PMID- 26896678 TI - Pericarditis with anaemia as a herald syndrome in a fatal presentation of cardiac lymphoma. AB - Primary cardiac lymphoma (PCL) is rare, accounting for 2% of all primary cardiac malignancies. Diagnosis is sometimes slow due to the non-specific nature of symptoms, causing a delay to treatment with potentially curative anthracycline chemotherapy. We report an unusual presentation of primary cardiac lymphoma in an immunocompetent man presenting with subacute isolated right-sided heart failure with pericarditis on a background of chronic anaemia and constitutional upset. Echocardiography demonstrated a pericardial mass invading the right atrium and compressing the tricuspid annulus. Diffuse large B-cell lymphoma was diagnosed after biopsy. This case highlights the importance of early imaging and hospitalisation in pericarditis with high-risk features such as high inflammatory markers, myocardial involvement (with troponin elevation), fever, immunosuppression or evidence of heart failure. The differential and diagnostic pathway of an intracardiac mass, and the treatment and prognosis of PCL, are discussed. PMID- 26896679 TI - Kaposi sarcoma: an unusual cause of gastrointestinal bleeding. PMID- 26896680 TI - A note on "an erroneous formula in use for estimating radon exhalation rates from samples using sealed can technique". AB - In this note, we point out a serious fallacy in a formula that has appeared in literature for calculating the (222)Rn exhalation rates using the Solid-State Nuclear Track Detector (SSNTD) based sealed can technique. It is shown that this formula underestimates true exhalation rates by a factor of more than 10(6). Several publications have used this formula instead of the well-known Abu-Jarad formula and have reported unrealistically low (uBq/m(2)/d) surface exhalation rates for normal materials. PMID- 26896681 TI - Measurement of residence time distribution of liquid phase in an industrial-scale continuous pulp digester using radiotracer technique. AB - A series of radiotracer experiments was carried out to measure residence time distribution (RTD) of liquid phase (alkali) in an industrial-scale continuous pulp digester in a paper industry in India. Bromine-82 as ammonium bromide was used as a radiotracer. Experiments were carried out at different biomass and white liquor flow rates. The measured RTD data were treated and mean residence times in individual digester tubes as well in the whole digester were determined. The RTD was also analyzed to identify flow abnormalities and investigate flow dynamics of the liquid phase in the pulp digester. Flow channeling was observed in the first section (tube 1) of the digester. Both axial dispersion and tanks-in series with backmixing models preceded with a plug flow component were used to simulate the measured RTD and quantify the degree of axial mixing. Based on the study, optimum conditions for operating the digester were proposed. PMID- 26896683 TI - Extraction of high-quality RNA from pancreatic tissues for gene expression studies. AB - Extracting RNA from pancreatic tissue is notoriously challenging because of the organ's high RNase content. Standard methods using TriPure or TRIzol classically yield RNA of sufficient quality for routine gene expression analysis but not for microarray or deep sequencing analysis. Here we developed a simple method to extract high-quality RNA from mouse pancreas. Our method uses an RNase inhibitor and combines different protocols using guanidium thiocyanate-phenol extraction. It enables reproducible isolation of RNA with an RNA integrity number around 9. PMID- 26896682 TI - Recent applications of light scattering measurement in the biological and biopharmaceutical sciences. PMID- 26896684 TI - The oral cholera vaccine ShancholTM when stored at elevated temperatures maintains the safety and immunogenicity profile in Bangladeshi participants. AB - BACKGROUND: The oral cholera vaccine (OCV), ShancholTM has shown protective efficacy lasting up to 5 years, however, requirement for a cold chain limits its use in resource poor settings. The study was conducted to determine the safety and immunogenicity of Shanchol in adult participants in Bangladesh when stored at elevated temperatures. METHODS: The study was conducted in Mirpur, Dhaka. Four groups of healthy adult participants received two doses of ShancholTM, kept under standard storage temperature (Group A; 2-8 degrees C) or at elevated temperatures (Group B, 25 degrees C; Group C, 37 degrees C; Group D, 42 degrees C) for 14 days, respectively. Vaccine specific antibody responses were determined. FINDINGS: 145 participants were assigned to each group. Adverse events were mild not differing among groups. Vaccine stored at elevated temperatures remained stable with cumulative LPS content within admissible limits. Vibriocidal antibody responses were observed in all groups after each dose of vaccine at day 7 and 21 compared to pre-immune levels (P<0.001). Four-fold increases to Vibrio cholerae O1 Ogawa were observed at day 7 and/or day 21 after vaccination in the standard temperature and the three elevated temperature groups, with responder rates of; 76% (95% CI LB; 70%), 80% (95% CI LB; 74%), 69% (95% CI LB; 63%), and 74% (95% CI LB; 68%) in Groups A-D, respectively (P=0.240). Responses were also seen in all groups to V. cholerae O1 Inaba and V. cholerae O139 and in LPS specific IgA response to V. cholerae O1 antigens. INTERPRETATION: This is the first report to show that the OCV is stable at elevated temperatures, and the safety and immunogenicity profiles are not altered. This information will help formulate global policies for use of the vaccine at higher temperatures, resulting in easier distribution and vaccination costs and decrease logistical challenges to vaccine delivery. FUNDING: Bill & Melinda Gates Foundation. TRIAL REGISTRATION: Clinical Trials.gov number NCT01762930. PMID- 26896675 TI - A genome-wide resource for the analysis of protein localisation in Drosophila. AB - The Drosophila genome contains >13000 protein-coding genes, the majority of which remain poorly investigated. Important reasons include the lack of antibodies or reporter constructs to visualise these proteins. Here, we present a genome-wide fosmid library of 10000 GFP-tagged clones, comprising tagged genes and most of their regulatory information. For 880 tagged proteins, we created transgenic lines, and for a total of 207 lines, we assessed protein expression and localisation in ovaries, embryos, pupae or adults by stainings and live imaging approaches. Importantly, we visualised many proteins at endogenous expression levels and found a large fraction of them localising to subcellular compartments. By applying genetic complementation tests, we estimate that about two-thirds of the tagged proteins are functional. Moreover, these tagged proteins enable interaction proteomics from developing pupae and adult flies. Taken together, this resource will boost systematic analysis of protein expression and localisation in various cellular and developmental contexts. PMID- 26896685 TI - Influenza B vaccine lineage selection--an optimized trivalent vaccine. AB - Epidemics of seasonal influenza viruses cause considerable morbidity and mortality each year. Various types and subtypes of influenza circulate in humans and evolve continuously such that individuals at risk of serious complications need to be vaccinated annually to keep protection up to date with circulating viruses. The influenza vaccine in most parts of the world is a trivalent vaccine, including an antigenically representative virus of recently circulating influenza A/H3N2, A/H1N1, and influenza B viruses. However, since the 1970s influenza B has split into two antigenically distinct lineages, only one of which is represented in the annual trivalent vaccine at any time. We describe a lineage selection strategy that optimizes protection against influenza B using the standard trivalent vaccine as a potentially cost effective alternative to quadrivalent vaccines. PMID- 26896686 TI - Human Papillomavirus neutralizing and cross-reactive antibodies induced in HIV positive subjects after vaccination with quadrivalent and bivalent HPV vaccines. AB - Ninety-one HIV-infected individuals (61 men and 30 women) were randomized to vaccination either with quadrivalent (GardasilTM) or bivalent (CervarixTM) HPV vaccine. Neutralizing and specific HPV-binding serum antibodies were measured at baseline and 12 months after the first vaccine dose. Presence of neutralizing and binding antibodies had good agreement (average Kappa for HPV types 6, 11, 16, 18, 31, 33 and 45 was 0.65). At baseline, 88% of subjects had antibodies against at least one genital HPV. Following vaccination with CervarixTM, all subjects became seropositive for HPV16 and 18. After GardasilTM vaccination, 96% of subjects seroconverted for HPV16 and 73% for HPV18. Levels of HPV16-specific antibodies were <1 international unit (IU) in 87% of study subjects before vaccination but >10IU in 85% of study subjects after vaccination. Antibodies against non-vaccine HPV types appeared after GardasilTM vaccination for >50% of vaccinated females for HPV 31, 35 and 73 and for >50% of CervarixTM-vaccinated females for HPV 31, 33, 35, 45, 56 and 58. Cross-reactivity with non-genital HPV types was also detected. In conclusion, HIV-infected subjects responded to HPV vaccination with induction of neutralizing antibodies against both vaccine and non-vaccine types. PMID- 26896687 TI - Tip110: Physical properties, primary structure, and biological functions. AB - HIV-1 Tat-interacting protein of 110kDa (Tip110), also referred to as squamous cell carcinoma antigen recognized by T cells 3 (Sart3), p110 or p110(nrb), was initially identified as a cDNA clone (KIAA0156) without annotated functions. Over the past twenty years, several functions have been attributed to this protein. The proposed biological functions include roles for Tip110 in pre-mRNA splicing, gene transcription, stem cell biology, and development. Dysregulation of Tip110 is also a contributing factor in the development of cancer and other human diseases. It is clear that our understanding of this protein is rapidly evolving. In this review, we aimed to provide a summary of all the existing literature on this gene/protein and its proposed biological functions. PMID- 26896689 TI - Phase angle is associated with advanced fibrosis in patients chronically infected with hepatitis C virus. AB - AIMS: The objective of this study was to evaluate the association of phase angle (PhA) with advanced liver fibrosis in patients chronically infected with hepatitis C virus (HCV). MAIN METHODS: One hundred sixty consecutive patients chronically infected with HCV were treated at the Hepatitis C outpatient care setting of our hospital from April 2010 to May 2011 and prospectively evaluated. Bioelectrical impedance analysis measurements were performed during the first hospital visit. Biochemical measurements and liver biopsy data were collected from the patients' medical records and included in the analysis only if they were performed within three months of the inclusion of the patient in the study. KEY FINDINGS: One hundred sixty consecutive patients were evaluated and 25 patients were excluded. A total of 135 patients with 49.8+/-11.4years old were studied. Among these patients, 60% were male and the PhA was 6.5+/-0.8 degrees . Regarding the stage of fibrosis, patients with advanced fibrosis were older and had more insulin resistance and more inflammation compared with patients that had mild fibrosis. Logistic regression analysis revealed that PhA was a predictor of advanced fibrosis even when adjusted for gender, age, HOMA-IR, HDL-cholesterol and AST (OR: 0.227; CI 95%: 0.090-0.569; p: 0.013). The best PhA cut-off points associated with advanced fibrosis for the combined data, for females and for males were 6.43 degrees , 5.94 degrees and 6.72 degrees , respectively. SIGNIFICANCE: PhA was predictor of advanced liver fibrosis in patients chronically infected with HCV. In the sample evaluated, for each one-degree decrease in PhA, the risk of advanced fibrosis increased more than four-fold. PMID- 26896688 TI - Over-expression of miR-451a can enhance the sensitivity of breast cancer cells to tamoxifen by regulating 14-3-3zeta, estrogen receptor alpha, and autophagy. AB - AIM: To investigate the effects and mechanisms of miR-451a in the tamoxifen (TAM) resistance of breast cancer cells. MATERIALS AND METHODS: TAM sensitive cells (MCF-7) and resistant cells (LCC2) were employed in the study. The lentivirus vectors of Lv-miR-451a, Lv-miR-451a sponge, and Lv-miR-451a NC were employed to increase or decrease the expression of miR-451a, respectively. SiRNA to 14-3 3zeta was used to inhibit expression of 14-3-3zeta. MTT assay was utilized to detect breast cancer cell proliferation. AnnexinV-FITC binding assay was used to detect apoptosis. Expression of ERalpha, 14-3-3zeta and miR-451a were measured by qRT-PCR and Western blot analysis. Interactions between 14-3-3zeta and ERalpha were investigated by co-immunoprecipitation. LC3-II surface expression and intracellular autophagosomes were observed by Western blot and electron microscopy. KEY FINDINGS: Over-expression of miR-451a can enhance MCF-7 and LCC2 cell sensitivity to TAM. Opposite effects were elicited by knocking down miR 451a. TAM treatment can up-regulate 14-3-3zeta expression, and down-regulate ERalpha expression. 14-3-3zeta and ERalpha were shown to interact. Over expression of miR-451a decreased 14-3-3zeta expression and increased ERalpha expression, suppressing cell proliferation, increasing apoptosis, and reducing activation of p-AKT and p-mTOR. R18 can significantly decrease cell proliferation and increase apoptosis. R18 and 14-3-3zeta siRNA can rescue the effects of down regulation of ERalpha by knocking down miR-451a. Over-expression of miR-451a inhibits autophagy, knocking-down miR-451a stimulates autophagy. SIGNIFICANCE: MiR-451a functions as a suppressor of resistance to TAM through regulating autophagy, the expression of 14-3-3zeta and ERalpha. This suggests miR-451a to be a potential target for reversing resistance to TAM. PMID- 26896690 TI - Epidemiology of moderate-to-severe injury patterns observed in rollover crashes. AB - BACKGROUND: Previous epidemiological studies have highlighted the high risk of injury to the head, thorax, and cervical spine in rollover crashes. However, such results provide limited information on whole-body injury distribution and multiple region injury patterns necessary for the improvement and prioritization of rollover-focused injury countermeasures. METHODS: Sampled cases representing approximately 133,000 U.S. adult occupants involved in rollover crashes (between 1995 and 2013) sustaining moderate-to-severe injuries were selected from the National Automotive Sampling System Crashworthiness Data System database. A retrospective cohort study, based on a survey of population-based data, was used to identify relevant whole body injury patterns. RESULTS: Among belted occupants injured in rollover crashes, 79.2% sustained injuries to only one body region. The three most frequently injured (AIS2+) body regions were head (42.1%), upper extremity (28.0%), and thorax (27.1%). The most frequent multi-region injury pattern involved the head and upper extremity, but this pattern only accounted for 2.3% of all of occupants with moderate or worse injuries. CONCLUSIONS: The results indicated that for rollover-dominated crashes, the frequently observed injury patterns involved isolated body regions. In contrast, multi-region injury patterns are more frequently observed in rollovers with significant planar impacts. Identification of region-specific injury patterns in pure rollover crashes is essential for clarifying injury mitigation targets and developing whole-body injury metrics specifically applicable to rollovers. PMID- 26896691 TI - Biomechanical evaluation of a novel dynamic posterior cruciate ligament brace. AB - BACKGROUND: Use of a rigid brace or cast immobilization is recommended in conservative treatment or postoperative rehabilitation after a posterior cruciate ligament injury. To prevent the loss of knee joint function and muscle activity often associated with this, a flexible knee brace has been developed that allows an adjustable anteriorly directed force to be applied to the calf in order to prevent posterior tibial translation. The purpose of this biomechanical study was to evaluate the impact of this novel dynamic brace on posterior tibial translation after posterior cruciate ligament injury and reconstruction. METHODS: A Telos stress device was used to provoke posterior tibial translation in seven human lower limb specimens, and stress radiographs were taken at 90 degrees of knee flexion. Posterior tibial translation was measured in the native knees with an intact posterior cruciate ligament; after arthroscopic posterior cruciate ligament dissection with and without a brace; and after posterior cruciate ligament reconstruction with and without a brace. The force applied with the brace was measured using a pressure sensor. FINDINGS: Posterior tibial translation was significantly reduced (P=0.032) after application of the brace with an anteriorly directed force of 50N to the knees with the dissected posterior cruciate ligament. The brace also significantly reduced posterior tibial translation after posterior cruciate ligament reconstruction in comparison with reconstructed knees without a brace (P=0.005). INTERPRETATION: Posterior tibial translation was reduced to physiological values using this dynamic brace system that allows an anteriorly directed force to be applied to the calf. PMID- 26896692 TI - Cellular Mechanism for Impaired Hepatitis C Virus Clearance by Interferon Associated with IFNL3 Gene Polymorphisms Relates to Intrahepatic Interferon lambda Expression. AB - The single nucleotide polymorphism located within the IFNL3 (also known as IL28B) promoter is one of the host factors associated with hepatitis C virus (HCV) clearance by interferon (IFN)-alpha therapy; however the mechanism remains unknown. We investigated how IL28B gene polymorphism influences HCV clearance with infected primary human hepatocytes, liver biopsies, and hepatoma cell lines. Our study confirms that the rs12979860-T/T genotype has a strong correlation with ss469415590-DeltaG/DeltaG single nucleotide polymorphism that produces IFN lambda4 protein. We found that IFN-alpha and IFN-lambda1 antiviral activity against HCV was impaired in IL28B T/T infected hepatocytes compared with C/C genotype. Western blot analysis showed that IL28B TT genotype hepatocytes expressed higher levels of IFN-lambda proteins (IL28B, IL-29), preactivated IFN stimulated gene (ISG) expression, and impaired Stat phosphorylation when stimulated with either IFN-alpha or IFN-lambda1. Furthermore, we showed that silencing IFN-lambda1 in T/T cell line reduced basal ISG expression and improved antiviral activity. Likewise, overexpression of IFN-lambda (1 to 4) in C/C cells induced basal ISG expression and prevented IFN-alpha antiviral activity. We showed that IFN-lambda4, produced at low level only in T/T cells induced expression of IL28B and IL-29 and prevented IFN-alpha antiviral activity in HCV cell culture. Our results suggest that IFN-lambda4 protein expression associated with the IL28B-T/T variant preactivates the Janus kinase-Stat signaling, leading to impaired HCV clearance by both IFN-alpha and IFN-lambda. PMID- 26896695 TI - The plant defensin NaD1 introduces membrane disorder through a specific interaction with the lipid, phosphatidylinositol 4,5 bisphosphate. AB - Plant defensins interact with phospholipids in bilayers as part of their cytotoxic activity. Solanaceous class II defensins with the loop 5 sequence pattern "S-[KR]-[ILVQ]-[ILVQ]-[KR]-[KR]" interact with PI(4,5)P2. Here, the prototypical defensin of this class, NaD1, is used to characterise the biophysical interactions between these defensins and phospholipid bilayers. Binding of NaD1 to bilayers containing PI(4,5)P2 occurs rapidly and the interaction is very strong. Dual polarisation interferometry revealed that NaD1 does not dissociate from bilayers containing PI(4,5)P2. Binding of NaD1 to bilayers with or without PI(4,5)P2 induced disorder in the bilayer. However, permeabilisation assays revealed that NaD1 only permeabilised liposomes with PI(4,5)P2 in the bilayer, suggesting a role for this protein-lipid interaction in the plasma membrane permeabilising activity of this defensin. No defensins in the available databases have the PI(4,5)P2 binding sequence outside the solanaceous class II defensins, leading to the hypothesis that PI(4,5)P2 binding co-evolved with the C-terminal propeptide to protect the host cell against the effects of the tight binding of these defensins to their cognate lipid as they travel along the secretory pathway. This data has allowed us to develop a new model to explain how this class of defensins permeabilises plasma membranes to kill target cells. PMID- 26896694 TI - Decrypting protein insertion through the translocon with free-energy calculations. AB - Protein insertion into a membrane is a complex process involving numerous players. The most prominent of these players is the Sec translocon complex, a conserved protein-conducting channel present in the cytoplasmic membrane of bacteria and the membrane of the endoplasmic reticulum in eukaryotes. The last decade has seen tremendous leaps forward in our understanding of how insertion is managed by the translocon and its partners, coming from atomic-detailed structures, innovative experiments, and well-designed simulations. In this review, we discuss how experiments and simulations, hand-in-hand, teased out the secrets of the translocon-facilitated membrane insertion process. In particular, we focus on the role of free-energy calculations in elucidating membrane insertion. Amazingly, despite all its apparent complexity, protein insertion into membranes is primarily driven by simple thermodynamic and kinetic principles. This article is part of a Special Issue entitled: Membrane proteins edited by J.C. Gumbart and Sergei Noskov. PMID- 26896693 TI - Multi-ion free energy landscapes underscore the microscopic mechanism of ion selectivity in the KcsA channel. AB - Potassium (K(+)) channels are transmembrane proteins that passively and selectively allow K(+) ions to flow through them, after opening in response to an external stimulus. One of the most critical functional aspects of their function is their ability to remain very selective for K(+) over Na(+) while allowing high throughput ion conduction at a rate close to the diffusion limit. Classically, it is assumed that the free energy difference between K(+) and Na(+) in the pore relative to the bulk solution is the critical quantity at the origin of selectivity. This is the thermodynamic view of ion selectivity. An alternative view assumes that kinetic factors play the dominant role. Recent results from a number of studies have also highlighted the great importance of the multi-ion single file on the selectivity of K(+) channels. The data indicate that having multiple K(+) ions bound simultaneously is required for selective K(+) conduction, and that a reduction in the number of bound K(+) ions destroys the multi-ion selectivity mechanism utilized by K(+) channels. In the present study, multi-ion potential of mean force molecular dynamics computations are carried out to clarify the mechanism of ion selectivity in the KcsA channel. The computations show that the multi-ion character of the permeation process is a critical element for establishing the selective ion conductivity through K(+)-channels. This article is part of a Special Issue entitled: Membrane Proteins edited by J.C. Gumbart and Sergei Noskov. PMID- 26896696 TI - Specific characteristics of abnormal general movements are associated with functional outcome at school age. AB - BACKGROUND: Assessing the quality of general movements (GMs) is a non-invasive tool to identify at early age infants at risk for developmental disorders. AIM: To investigate whether specific characteristics of definitely abnormal GMs are associated with developmental outcome at school age. STUDY DESIGN: Observational cohort study (long-term follow-up). SUBJECTS: Parents of 40 children (median age 8.3 years, 20 girls) participated in this follow-up study. In infancy (median corrected age 10 weeks), the children (median gestational age 30.3 weeks; birth weight 1243 g) had shown definitely abnormal GMs according to Hadders-Algra (2004). Information on specific GM characteristics such as the presence of fidgety movements, degree of complexity and variation, and stiff movements, was available (see Hamer et al. 2011). OUTCOME MEASURES: A standardised parental interview (presence of CP, attendance of school for special education, Vineland Adaptive Behavior Scale to determine functional performance) and questionnaires (Developmental Coordination Disorder Questionnaire [DCD-Q] to evaluate mobility and Child Behavior Checklist to assess behaviour) were used as outcome measures. RESULTS: Six children had cerebral palsy (CP), ten children attended a school for special education, and eight children had behavioural problems. Both the absence of fidgety movements and the presence of stiff movements were associated with CP (p=0.001; p=0.003, respectively). Stiff movements were also related to the need of special education (p=0.009). A lack of movement complexity and variation was associated with behavioural problems (p=0.007). None of the GM characteristics were related to DCD-Q scores. CONCLUSIONS: The evaluation of fidgety movements and movement stiffness may increase the predictive power of definitely abnormal GMs for motor outcome--in particular CP. This study endorses the notion that the quality of GMs reflects the integrity of the infant's brain, assisting prediction of long-term outcome. PMID- 26896697 TI - Abnormal visual experience during development alters the early stages of visual tactile integration. AB - Visual experience during the critical periods in early postnatal life is necessary for the normal development of the visual system. Disruption of visual input during this period results in amblyopia, which is associated with reduced activation of the striate and extrastriate cortices. It is well known that visual input converges with other sensory signals and exerts a significant influence on cortical processing in multiple association areas. Recent work in healthy adults has also shown that task-relevant visual input can modulate neural excitability at very early stages of information processing in the primary somatosensory cortex. Here we used electroencephalography to investigate visual-tactile interactions in adults with abnormal binocular vision due to amblyopia and strabismus. Results showed three main findings. First, in comparison to a visually normal control group, participants with abnormal vision had a significantly lower amplitude of the P50 somatosensory event related potential (ERP) when visual and tactile stimuli were presented concurrently. Second, the amplitude of the P100 somatosensory ERP was significantly greater in participants with abnormal vision. These results indicate that task relevant visual input does not significantly influence the excitability of the primary somatosensory cortex, instead, the excitability of the secondary somatosensory cortex is increased. Third, participants with abnormal vision had a higher amplitude of the P1 visual ERP when a tactile stimulus was presented concurrently. Importantly, these results were not modulated by viewing condition, which indicates that the impact of amblyopia on crossmodal interactions is not simply related to the reduced visual acuity as it was evident when viewing with the unaffected eye and binocularly. These results indicate that the consequences of abnormal visual experience on neurophysiological processing extend beyond the primary and secondary visual areas to other modality-specific areas. PMID- 26896698 TI - Multifaceted effects of host plants on entomopathogenic nematodes. AB - The success of parasites can be impacted by multi-trophic interactions. Tritrophic interactions have been observed in parasite-herbivore-host plant systems. Here we investigate aspects of multi-trophic interactions in a system involving an entomopathogenic nematode (EPN), its insect host, and host plant. Novel issues investigated include the impact of tritrophic interactions on nematode foraging behavior, the ability of EPNs to overcome negative tritrophic effects through genetic selection, and interactions with a fourth trophic level (nematode predators). We tested infectivity of the nematode, Steinernema riobrave, to corn earworm larvae (Helicoverpa zea) in three host plants, tobacco, eggplant and tomato. Tobacco reduced nematode virulence and reproduction relative to tomato and eggplant. However, successive selection (5 passages) overcame the deficiency; selected nematodes no longer exhibited reductions in phenotypic traits. Despite the loss in virulence and reproduction nematodes, first passage S. riobrave was more attracted to frass from insects fed tobacco than insects fed on other host plants. Therefore, we hypothesized the reduced virulence and reproduction in S. riobrave infecting tobacco fed insects would be based on a self-medicating tradeoff, such as deterring predation. We tested this hypothesis by assessing predatory success of the mite Sancassania polyphyllae and the springtail Sinella curviseta on nematodes reared on tobacco-fed larvae versus those fed on greater wax moth, Galleria mellonella, tomato fed larvae, or eggplant fed larvae. No advantage was observed in nematodes derived from tobacco fed larvae. In conclusion, our results indicated that insect-host plant diet has an important effect on nematode foraging, infectivity and reproduction. However, negative host plant effects, might be overcome through directed selection. We propose that host plant species should be considered when designing biocontrol programs using EPNs. PMID- 26896699 TI - Computational modeling of acrylodan-labeled cAMP dependent protein kinase catalytic subunit unfolding. AB - Structure of the cAMP-dependent protein kinase catalytic subunit, where the asparagine residue 326 was replaced with acrylodan-cystein conjugate to implement this fluorescence reporter group into the enzyme, was modeled by molecular dynamics (MD) method and the positioning of the dye molecule in protein structure was characterized at temperatures 300K, 500K and 700K. It was found that the acrylodan moiety, which fluorescence is very sensitive to solvating properties of its microenvironment, was located on the surface of the native protein at 300K that enabled its partial solvation with water. At high temperatures the protein structure significantly changed, as the secondary and tertiary structure elements were unfolded and these changes were sensitively reflected in positioning of the dye molecule. At 700K complete unfolding of the protein occurred and the reporter group was entirely expelled into water. However, at 500K an intermediate of the protein unfolding process was formed, where the fluorescence reporter group was directed towards the protein interior and buried in the core of the formed molten globule state. This different positioning of the reporter group was in agreement with the two different shifts of emission spectrum of the covalently bound acrylodan, observed in the unfolding process of the protein. PMID- 26896700 TI - What Extrapolation Could Mean for Your Practice: A Legal Overview of Statistical Sampling in Overpayment and False Claims Act Cases. AB - Auditors in Medicare overpayment or False Claims Act (FCA) cases often use statistical extrapolation to estimate a health-care provider's total liability from a small sample of audited claims. Courts treat statistical extrapolation differently depending on the context. They generally afford the government substantial discretion in using statistical extrapolation in overpayment cases. By contrast, courts typically more closely scrutinize the use of extrapolation in FCA cases involving multiple damages and civil penalties to ensure that the sample truly reflects the entire universe of claims and that the extrapolation rests on a sound methodological foundation. In recent cases, however, multiple courts have allowed the use of extrapolation in FCA cases. When auditors attempt to use statistical extrapolation, providers should closely inspect the sample and challenge the extrapolation when any reasonable argument exists that the sample does not constitute a reliable or accurate representation of all the provider's claims. PMID- 26896701 TI - The Presence of Diffuse Alveolar Damage on Open Lung Biopsy Is Associated With Mortality in Patients With Acute Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis. AB - OBJECTIVE: Diffuse alveolar damage (DAD) is considered the histologic hallmark of ARDS although DAD is absent in approximately half of patients with ARDS. The clinical implications of having the syndrome of ARDS with DAD vs other histologic patterns is unknown. To address this question, we conducted a meta-analysis of lung biopsy series for patients with ARDS. METHODS: Studies were identified using MEDLINE, EMBASE, Cochrane Register of Controlled Trials, LILACS, and citation review from January 1, 1967, to September 1, 2015. Studies were included if they included all of the following: open lung biopsies (OLB) performed after ARDS diagnosis; a clear definition of ARDS and DAD; histologic results of the OLB indicated the presence or absence of DAD; and mortality reported for the DAD and non-DAD groups. We excluded studies conducted solely on a specific histology subgroup (eg, DAD) and studies with fewer than 5 patients. Two authors independently selected studies for inclusion, and there were no language restrictions. RESULTS: Of 8 included studies, 4 were high-quality (n = 228) and 4 were middle-quality trials (n = 122). The meta proportion of DAD between all the groups was 0.45 (95% CI, 0.35-0.56; Q test, 21.1; I(2), 66.8%; P <= .01). The pooled OR for mortality in ARDS with DAD compared with ARDS without DAD was 1.81 (95% CI, 1.14-2.80; Q test, 8.8; I(2), 20.2%; P = .269). Age, sex, and days elapsed between ARDS diagnosis and OLB as well as sequential organ failure assessment score and Pao2/Fio2 ratio on the day of OLB did not differ between DAD and non-DAD groups. CONCLUSIONS: This meta-analysis demonstrated that ARDS with DAD is associated with higher mortality than ARDS without DAD. PMID- 26896702 TI - Clinical Utility of a Bronchial Genomic Classifier in Patients With Suspected Lung Cancer. AB - BACKGROUND: Bronchoscopy is often the initial diagnostic procedure performed in patients with pulmonary lesions suggestive of lung cancer. A bronchial genomic classifier was previously validated to identify patients at low risk for lung cancer after an inconclusive bronchoscopy. In this study, we evaluated the potential of the classifier to reduce invasive procedure utilization in patients with suspected lung cancer. METHODS: In two multicenter trials of patients undergoing bronchoscopy for suspected lung cancer, the classifier was measured in normal-appearing bronchial epithelial cells from a mainstem bronchus. Among patients with low and intermediate pretest probability of cancer (n = 222), subsequent invasive procedures after an inconclusive bronchoscopy were identified. Estimates of the ability of the classifier to reduce unnecessary procedures were calculated. RESULTS: Of the 222 patients, 188 (85%) had an inconclusive bronchoscopy and follow-up procedure data available for analysis. Seventy-seven (41%) patients underwent an additional 99 invasive procedures, which included surgical lung biopsy in 40 (52%) patients. Benign and malignant diseases were ultimately diagnosed in 62 (81%) and 15 (19%) patients, respectively. Among those undergoing surgical biopsy, 20 (50%) were performed in patients with benign disease. If the classifier had been used to guide decision making, procedures could have been avoided in 50% (21 of 42) of patients undergoing further invasive testing. Further, among 35 patients with an inconclusive index bronchoscopy who were diagnosed with lung cancer, the sensitivity of the classifier was 89%, with 4 (11%) patients having a false negative classifier result. CONCLUSIONS: Invasive procedures after an inconclusive bronchoscopy occur frequently, and most are performed in patients ultimately diagnosed with benign disease. Using the genomic classifier as an adjunct to bronchoscopy may reduce the frequency and associated morbidity of these invasive procedures. TRIAL REGISTRY: ClinicalTrials.gov; Nos. NCT01309087 and NCT00746759; URL: www.clinicaltrials.gov. PMID- 26896704 TI - Antimicrobial resistance and the growing threat of drug-resistant tuberculosis. PMID- 26896703 TI - Foot orthotics for low back pain: The state of our understanding and recommendations for future research. AB - PURPOSE: The purpose of the article is to evaluate the literature on the use of foot orthotics for low back pain and to make specific recommendations for future research. METHODS: Database searches were conducted using PubMed, EBSCO, GALE, Google Scholar, and clinicaltrials.gov. The biomedical literature was reviewed to determine the current state of knowledge on the benefits of foot orthotics for low back pain related to biomechanical mechanisms and clinical outcomes. RESULTS: It may be argued that foot orthotics are experimental, investigational, or unproven for low back pain due to lack of sufficient evidence for their clinical effectiveness. This conclusion is based upon lack of high quality randomized controlled trials (RCTs). However, there is extensive research on biomechanical mechanisms underlying the benefits of orthotics that may be used to address this gap. Additionally, promising pilot studies are beginning to emerge in the literature and ongoing large-scale RCTs are addressing effects of foot orthotics on chronic low back pain. CONCLUSIONS: Based upon the critical evaluation of the current research on foot orthotics related to biomechanical mechanisms and clinical outcomes, recommendations for future research to address the evidence practice gaps on the use of foot orthotics for low back pain are presented. PMID- 26896706 TI - Design and synthesis of novel tamoxifen analogues that avoid CYP2D6 metabolism. AB - Tamoxifen (TAM) is a widely used drug in the prophylaxis and treatment of breast cancer. TAM is metabolized to the more active 4-hydroxytamoxifen (4-OH-TAM) and endoxifen by cytochrome P450 (CYP) mainly CYP2D6 and CYP3A4 enzymes. Due to the genetic polymorphisms in CYP2D6 genes, high variation in the clinical outcomes of TAM treatment is observed among women of different populations. To address this issue, novel TAM analogues with possible altered activation pathways were synthesized. These analogues were tested for their antiproliferative action on MCF-7 breast cancer cell lines as well as their binding affinity for estrogen receptor (ER) ER-alpha and ER-beta receptors. These entire novel compounds showed better antiproliferative activity than did TAM on the MCF-7 cells. Moreover, compound 10 exhibited a half maximal growth inhibition (GI50) that was 1000 times more potent than that of TAM (GI50 < 0.005 MUM vs 1.58 MUM, respectively). Along with a broad spectrum activity on various cancer cell lines, all the TAM analogues showed considerable activity on the ER-negative breast cancer cell line. For further study, compound 10 was incubated in human liver microsomes (HLM), human hepatocytes (hHEP) and CYP2D6 supersomes. The active hydroxyl metabolite was detected after incubation in HLM and hHEP, implicating the involvement of other enzymes in its metabolism. These results prove that this novel series of TAM analogues might provide improved clinical outcomes for poor 2D6 metabolizers. PMID- 26896705 TI - The natural diterpene tonantzitlolone A and its synthetic enantiomer inhibit cell proliferation and kinesin-5 function. AB - Tonantzitlolone A, a diterpene isolated from the Mexican plant Stillingia sanguinolenta, shows cytostatic activity. Both the natural product tonantzitlolone A and its synthetic enantiomer induce monoastral spindle formation in cell experiments which indicates inhibitory activity on kinesin-5 mitotic motor molecules. These inhibitory effects on kinesin-5 could be verified in in vitro single-molecule motility assays, where both tonantzitlolones interfered with kinesin-5 binding to its cellular interaction partner microtubules in a concentration-dependent manner, yet with a larger effect of the synthetic enantiomer. In contrast to kinesin-5 inhibition, both tonantzitlolone A enantiomers did not affect conventional kinesin-1 function; hence tonantzitlolones are not unspecific kinesin inhibitors. The observed stronger inhibitory effect of the synthetic enantiomer demonstrates the possibility to enhance the overall moderate anti-proliferative effect of the lead compound tonantzitlolon A by chemical modification. PMID- 26896707 TI - Antifibrotic and anticancer action of 5-ene amino/iminothiazolidinones. AB - Here we describe the synthesis and the antifibrotic and anticancer activity determination of amino(imino)thiazolidinone derivatives. An efficient one-pot three-component reaction which involved [2 + 3]-cyclocondensation and Knoevenagel condensation was used for the synthesis of 5-ene-2-amino(imino)-4 thiazolidinones. Following amino-imino tautomerism, the compound structures were confirmed by X-ray analysis. Comparison of SRB assays on fibroblasts and cancer cells revealed that compounds which significantly reduced the viability of fibroblasts did not possess an anticancer effect. A series of thiazolidinone derivatives as interesting candidates for further testing has been identified. Among the tested compounds 2-{3-furan-2-ylmethyl-2-[(2-methyl-3 phenylallylidene)hydrazono]-thiazolidin-4-one-5-yl}-N-(3-trifluoromethylphenyl) acetamide (5), N-(2-methoxyphenyl)-2-[5-(4-oxothiazolidin-2-ylideneamino) [1,3,4]thiadiazol-2-ylsulfanyl]-acetamide (12), 3-[3-allyl-4-oxo-2-(thiazol-2 ylimino)thiazolidin-5-ylidene]-1,3-dihydroindol-2-one (33), and 5(Z)-(thiophen-2 ylmethylene)-4-(4-chlorophenylamino)thiazol-2(5H)-one (34) possessed high antifibrotic activity levels, had a similar effect as Pirfenidone, and did not scavenge superoxide radicals. Their antifibrotic potential was confirmed using the xCelligence system. PMID- 26896708 TI - Phosphoramidate protides of five flavones and their antiproliferative activity against HepG2 and L-O2 cell lines. AB - A series of flavone-7-phosphoramidate derivatives were synthesized and tested for their antiproliferative activity in vitro against human hepatoma cell line HepG2 and human normal hepatic cell line L-O2. Compound 8d, 16d and 17d, incorporating the amino acid alanine, exhibited high inhibitory activity on HepG2 cell line with IC50 values of 9.0 MUmol/L, 5.5 MUmol/L and 6.6 MUmol/L. The introduction of acyl groups played a pivotal role in the selective inhibition toward human hepatoma HepG2 cells, except for compound 8a, 9a and 16b. Compound 8d, 16d and 17d could significantly induce G2/M arrest in HepG2 cells. Specially, Compound 16d could lead early apoptosis in HepG2 cells. PMID- 26896709 TI - Systematic diversification of benzylidene heterocycles yields novel inhibitor scaffolds selective for Dyrk1A, Clk1 and CK2. AB - The dual-specificity tyrosine-regulated kinase 1A (Dyrk1A) has gathered much interest as a pharmacological target in Alzheimer's disease (AD), but it plays a role in malignant brain tumors as well. As both diseases are multi-factorial, further protein kinases, such as Clk1 and CK2, were proposed to contribute to the pathogenesis. We designed a new class of alpha-benzylidene-gamma-butyrolactone inhibitors that showed low micromolar potencies against Dyrk1A and/or Clk1 and a good selectivity profile among the most frequently reported off-target kinases. A systematic replacement of the heterocyclic moiety gave access to further inhibitor classes with interesting selectivity profiles, demonstrating that the benzylidene heterocycles provide a versatile tool box for developing inhibitors of the CMGC kinase family members Dyr1A/1B, Clk1/4 and CK2. Efficacy for the inhibition of Dyrk1A-mediated tau phosphorylation was demonstrated in a cell based assay. Multi-targeted but not non-specific kinase inhibitors were also obtained, that co-inhibited the lipid kinases PI3Kalpha/gamma. These compounds were shown to inhibit the proliferation of U87MG cells in the low micromolar range. Based on the molecular properties, the inhibitors described here hold promise for CNS activity. PMID- 26896710 TI - Aptima HIV-1 Quant Dx--A fully automated assay for both diagnosis and quantification of HIV-1. AB - BACKGROUND: Separate assays are available for diagnosis and viral load (VL) monitoring of HIV-1. Studies have shown that using a single test for both confirmatory diagnosis and VL increases linkage to care. OBJECTIVE: To validate a single assay for both diagnosis and VL monitoring of HIV-1 on the fully automated Panther platform. STUDY DESIGN: Validate the assay by assessing specificity, sensitivity, subtype detection, seroconversion, reproducibility and linearity. Also assess diagnostic agreement with the Procleix((r)) Ultrio EliteTM discriminatory assay (Procleix), and agreement of VL results (method comparison) with Ampliprep/COBAS TaqMan HIV-1 version 2.0 (CAP/CTM), using clinical samples. RESULTS: The assay was specific (100%) and sensitive with a 95% limit of detection of 12 copies/mL with the 3rd WHO standards. Aptima detected HIV in seroconversion panels 6 and 11 days before p24 antigen and antibody tests, respectively. Diagnostic agreement with Procleix, was 100%. Regression analysis showed good agreement of VL results between Aptima and CAP/CTM with a slope of 1.02, intercept of 0.07, and correlation coefficient (R(2)) of 0.97. Aptima was more sensitive than CAP/CTM. Equivalent quantification was seen on testing clinical samples and isolates belonging to HIV group M, N, O and P and commercially available subtype panels. Assay results were linear (R(2) 0.9994) with standard deviation of <0.17 log copies across assay range. CONCLUSIONS: The good specificity, sensitivity, precision, subtype performance and clinical agreement with other assays demonstrated by Aptima combined with the complete automation provided by the Panther platform makes Aptima a good candidate for both VL monitoring and diagnosis of HIV-1. PMID- 26896711 TI - Does physical exercise improve obstacle negotiation in the elderly? A systematic review. AB - BACKGROUND: Physical exercise improves walking in the elderly but much less is known about its effect on more challenged gait, such as obstacle negotiation. We conducted a systematic review to discuss the effects of regular physical exercise on kinematics and kinetics of obstacle negotiation in the elderly. METHODS: A comprehensive literature search revealed 859 citations for review, whereof 206 studies entered the full-text analysis. After application of inclusion and exclusion criteria, 13 studies were included in this systematic review. FINDINGS: Most of them presented a reasonable quality (average 0.68) but none of them reached the level of a randomized control trial. Interventions were heterogeneous, with training periods lasting from 5 days to 10 months. Studies assessed obstacle negotiation basically considering 3 types of testing paradigm, namely a walkway with either a single obstacle crossing, or with multiple obstacles, or else a treadmill with an obstacle avoidance task under time pressure. INTERPRETATION: In general, longer training programs had better results and very short ones were not effective. A weekly frequency of 2-3 times was the most common among the studies showing positive effects. Regardless of exercises types performed, most of them were effective and so far, there is no consensus about the best exercise for improving obstacle negotiation. A lack of studies on this topic still is evident. Including a record of fall score can further help in deciding which programs are to be preferred. PMID- 26896712 TI - Uses of miscanthus press juice within a green biorefinery platform. AB - This study assesses some uses of nutrient-rich juice mechanically extracted from freshly harvested Miscanthus x giganteus (MxG) as part of a green biorefinery system. The juice was used for culturing Saccharomyces cerevisiae and lactic acid bacteria. MxG juice was further used as substrate for fermentation to produce lactic acid using Lactobacillus brevis and Lactobacillus plantarum. The results show that MxG juice was a highly nutritious source for the cultivation of bacteria. Higher concentrations of MxG juice used as culture media, resulted in higher cell growth both aerobically and anaerobically. The highest ethanol yield of 70% theoretical and concentration of 0.75g/100ml were obtained from S. cerevisiae cultivated with 90% (v/v) MxG juice media and used for miscanthus solid fraction fermentation. 11.91g/L of lactic acid was also successfully produced from MxG juice through SSF. PMID- 26896713 TI - Enhancing anaerobic digestion of cotton stalk by pretreatment with a microbial consortium (MC1). AB - Microbial pretreatment is beneficial in some anaerobic digestion systems, but the consortia used to date have not been able to effectively increase methane production from cotton stalk. In this study, a thermophilic microbial consortium (MC1) was used for pretreatment in order to enhance biogas and methane production yields. The results indicated that the concentrations of soluble chemical oxygen demand and volatile organic products increased significantly in the early stages of pretreatment. Ethanol, acetic acid, propionic acid, and butyric acid were the predominant volatile organic products in the MC1 hydrolysate. Biogas and methane production yields from cotton stalk were significantly increased following MC1 pretreatment. In addition, the methane production rate from the treated cotton stalk was greater than that from the untreated sample. PMID- 26896714 TI - Low energy emulsion-based fermentation enabling accelerated methane mass transfer and growth of poly(3-hydroxybutyrate)-accumulating methanotrophs. AB - Methane is a low-cost feedstock for the production of polyhydroxyalkanoate biopolymers, but methanotroph fermentations are limited by the low solubility of methane in water. To enhance mass transfer of methane to water, vigorous mixing or agitation is typically used, which inevitably increases power demand and operational costs. This work presents a method for accelerating methane mass transfer without agitation by growing methanotrophs in water-in-oil emulsions, where the oil has a higher solubility for methane than water does. In systems without agitation, the growth rate of methanotrophs in emulsions is five to six times that of methanotrophs in the medium-alone incubations. Within seven days, cells within the emulsions accumulate up to 67 times more P3HB than cells in the medium-alone incubations. This is achieved due to the increased interfacial area of the aqueous phase, and accelerated methane diffusion through the oil phase. PMID- 26896715 TI - Simultaneous removal of chromate and nitrate in a packed-bed bioreactor using biodegradable meal box as carbon source and biofilm carriers. AB - An up-flow packed-bed bioreactor was constructed to investigate the simultaneous removal of chromate and nitrate using biodegradable meal box as carbon source and biofilm carriers. The bioreactor was operated for 164days with varying influent Cr(VI) concentrations (2.0-50.0mg/L) and hydraulic retention times (HRT, 10-24h). It was shown that complete denitrification and Cr(VI) reduction could be achieved when influent Cr(VI) concentrations were lower than 20mg/L with a HRT of 17h. Shortening the HRT could significantly reduce the effluent CODcr. It was also observed that Cr(III) was mainly immobilized on the biofilm. Further investigation on Cr distribution in the biofilm compartments indicated that Cr(VI) reduction occurred in all compartments and the intercellular Cr was dominant. High-throughput sequencing analysis showed that Proteobacteria, Bacteroidetes and Firmicutes were the dominant phyla in the biofilm and Cr(VI) stress had a negative effect on the abundance of most bacteria. PMID- 26896717 TI - Denitrifying phosphorus removal from municipal wastewater and dynamics of "Candidatus Accumulibacter" and denitrifying bacteria based on genes of ppk1, narG, nirS and nirK. AB - Relevance of clade-level population dynamics of "Candidatus Accumulibacter" to performance of denitrifying phosphorus (P) removal from municipal wastewater was investigated. Stable denitrifying P removal in anoxic zone of continuous-flow reactor was achieved, accounting for 90% of total P removal. Clades IIC and IIF affiliated with Accumulibacter lineage were the dominant clades during denitrifying P removal, reaching 90% of ppk1 clone library. NarG gene library indicated Gamma and Beta-proteobacteria played an important role in nitrate reduction. Diversity and abundance of nirS library was much more than nirK, and thus became the main functional gene to execute nitrite reduction. Based on abundance of nirS, nirK and ppk1, the ratio of Accumulibacter capable of denitrifying P removal to total Accumulibacter was 22%. No matter whether Accumulibacter had narG gene or not, high abundance of narG at a level of 10(9)cells/(g dried-sludge) promoted nitrate reduced to nitrite, ensuring performance of denitrifying P removal. PMID- 26896716 TI - Hydrolyzed polyacrylamide biodegradation and mechanism in sequencing batch biofilm reactor. AB - An investigation was performed to study the performance of a sequencing batch biofilm reactor (SBBR) to treat hydrolyzed polyacrylamides (HPAMs) and to determine the mechanisms of HPAM biodegradation. The mechanisms for the optimized parameters that significantly improved the degradation efficiency of the HPAMs were investigated by a synergistic effect of the co-metabolism in the sludge and the enzyme activities. The HPAM and TOC removal ratio reached 54.69% and 70.14%. A significant decrease in the total nitrogen concentration was measured. The carbon backbone of the HPAMs could be degraded after the separation of the amide group according to the data analysis. The HPLC results indicated that the HPAMs could be converted to polymer fragments without the generation of the acrylamide monomer intermediate. The results from high-throughput sequencing analysis revealed proteobacterias, bacteroidetes and planctomycetes were the key microorganisms involved in the degradation. PMID- 26896719 TI - Effect of biochar amendment on the control of soil sulfonamides, antibiotic resistant bacteria, and gene enrichment in lettuce tissues. AB - Considering the potential threat of vegetables growing in antibiotic-polluted soil with high abundance of antibiotic-resistant genes (ARGs) against human health through the food chain, it is thus urgent to develop novel control technology to ensure vegetable safety. In the present work, pot experiments were conducted in lettuce cultivation to assess the impedance effect of biochar amendment on soil sulfonamides (SAs), antibiotic-resistant bacteria (ARB), and ARG enrichment in lettuce tissues. After 100 days of cultivation, lettuce cultivation with biochar amendment exhibited the greatest soil SA dissipation as well as the significant improvement of lettuce growth indices, with residual soil SAs mainly existing as the tightly bound fraction. Moreover, the SA contents in roots and new/old leaves were reduced by one to two orders of magnitude compared to those without biochar amendment. In addition, isolate counts for SA-resistant bacterial endophytes in old leaves and sul gene abundances in roots and old leaves also decreased significantly after biochar application. However, neither SA resistant bacteria nor sul genes were detected in new leaves. It was the first study to demonstrate that biochar amendment can be a practical strategy to protect lettuce safety growing in SA-polluted soil with rich ARB and ARGs. PMID- 26896718 TI - Crystal structure of equine serum albumin in complex with cetirizine reveals a novel drug binding site. AB - Serum albumin (SA) is the main transporter of drugs in mammalian blood plasma. Here, we report the first crystal structure of equine serum albumin (ESA) in complex with antihistamine drug cetirizine at a resolution of 2.1A. Cetirizine is bound in two sites--a novel drug binding site (CBS1) and the fatty acid binding site 6 (CBS2). Both sites differ from those that have been proposed in multiple reports based on equilibrium dialysis and fluorescence studies for mammalian albumins as cetirizine binding sites. We show that the residues forming the binding pockets in ESA are highly conserved in human serum albumin (HSA), and suggest that binding of cetirizine to HSA will be similar. In support of that hypothesis, we show that the dissociation constants for cetirizine binding to CBS2 in ESA and HSA are identical using tryptophan fluorescence quenching. Presence of lysine and arginine residues that have been previously reported to undergo nonenzymatic glycosylation in CBS1 and CBS2 suggests that cetirizine transport in patients with diabetes could be altered. A review of all available SA structures from the PDB shows that in addition to the novel drug binding site we present here (CBS1), there are two pockets on SA capable of binding drugs that do not overlap with fatty acid binding sites and have not been discussed in published reviews. PMID- 26896720 TI - Temporal dynamics of urbanization-driven environmental changes explored by metal contamination in surface sediments in a restoring urban wetland park. AB - Spatial patterns of metal distribution along urban-rural or multi-city gradients indicate that the urbanization process directly lead to metal enrichment and contamination in the environments. However, it has not yet looked at homogenization dynamics of an urban-rural gradient pattern over time with urbanization process in an area. This study monitored anthropogenic metals (Cr, Cu, Pb, and Zn) in surface sediments from channels of a newly-opened National Wetland Park to elucidate the urbanization-driven dissolution of urban-rural gradient pattern between 2008 and 2011. Sixty-eight surface sediment samples were taken from these channels in July of both 2008 and 2011. Results showed that a spatial distribution pattern of total metal contents along the gradient of urbanization influence, evident in 2008, was homogenized in 2011 with the area development. The lead stable isotope ratio analysis identified anthropogenic Pb origins from vehicular exhausts, cements, and coal flying ashes, which elevated metal contents in the inner channels via atmospheric deposition. Specific hazard quotients of the metal contamination in surface sediment were also assessed and enhanced over time in the study wetland park. These findings suggest that emissions from traffic, construction, and energy generation contribute metal loadings in the urbanizing environment. PMID- 26896721 TI - Conformational changes of Abeta (1-42) monomers in different solvents. AB - Amyloid proteins are known to be the main cause of numerous degenerative and neurodegenerative diseases. In general, amyloids are misfolded from monomers and they tend to have beta-strand formations. These misfolded monomers are then transformed into oligomers, fibrils, and plaques. It is important to understand the forming mechanism of amyloids in order to prevent degenerative diseases to occur. Abeta protein is a highly noticeable protein which causes Alzheimer's disease. It is reported that solvents affect the forming mechanism of Abeta amyloids. In this research, Abeta1-42 was analyzed using an all-atom MD simulation with the consideration of effects induced by two disparate solvents: water and DMSO. As a result, two different conformation changes of Abeta1-42 were exhibited in each solvent. It was found that salt-bridge of Asp23 and Lys28 in Abeta1-42 was the key for amyloid folding based on the various analysis including hydrogen bond, electrostatic interaction energy and salt-bridge distance. Since this salt-bridge region plays a crucial role in initiating the misfolding of Abeta1-42, this research may shed a light for studies related in amyloid folding and misfolding. PMID- 26896723 TI - Educational attainment, time preference, and health-related behaviors: A mediation analysis from the J-SHINE survey. AB - Evidence consistently shows that low education is associated with unhealthy behaviors. A recent study in behavioral economics argued that high time preferences - the tendency to prefer immediate gain to later reward - explain the limited self-control of individuals in making preventive health-related choices. The aim of this study was to examine the mediating effect of time preference on the associations between education and smoking, binge drinking and overweight in young and middle-aged adults living in a Japanese metropolitan area, using a quantitatively measured time discount rate. A population-based probabilistic sample of residents of 25-50 years of age living in four municipalities within Japanese metropolitan areas where economic disparity is relatively large was obtained from the Japanese Study on Stratification, Health, Income, and Neighborhood (J-SHINE). Respondents answered the questionnaire items using a computer-aided personal instrument (CAPI). Data from 3457 respondents were used in this study. Time preferences measured as categorical responses were converted into a continuous number of time discount rates by using the maximum likelihood method. Smoking habit, binge drinking, and body mass index were regressed on educational attainment with demographics and other confounders. The mediating effects of the time discount rate were examined with the bootstrapping method. Results showed that the time discount rate did not mediate the association between education and binge drinking and BMI. Even for smoking, the mediating effect of time discount rate was quite limited, indicating that the proportion of total effect of education mediated was only 4.3% for men and 3.0% for women. The results suggest that modifying time preferences through educational intervention has only limited efficacy in closing disparities in health-related behaviors, and that other mediators fostered by schooling, such as knowledge/skills, group norms and supportive peers/networks, may be more important as modifiable mediators in the link between education and smoking. PMID- 26896722 TI - Gender difference in long-term clinical outcomes following percutaneous coronary intervention during 1984-2008. AB - BACKGROUND AND AIMS: Female has been demonstrated to be at higher risk following percutaneous coronary intervention (PCI) compared with male in unadjusted analyses. However, conflicting results were observed after adjustment of confounding factors. Particularly, more recent studies reported that gender differences have diminished possibly by evolution of PCI-related devices and evidence-based medical therapy. We aimed to examine gender differences in long term clinical outcomes following PCI during time period of 25 years. METHODS: This was a single center retrospective study in which consecutive patients who received the first PCI in our institution between January 1984 and December 2008 were analyzed. A composite of all-cause death and acute coronary syndrome (ACS) at 5-year after the index PCI was compared between genders. The endpoint was also examined in plain-old balloon angioplasty (POBA)-, bare metal stent (BMS)- and drug-eluting stent (DES)-eras separately. RESULTS: A total of 3531 patients (female; 605, male; 2926) were analyzed. The female patients had higher risk profiles than the male in terms of age, comorbid diseases, a prevalence of ACS, while male patients had a higher percentage of smoking, lower left ventricular ejection fraction (LVEF) and lower percentages of secondary prevention drugs. Gender difference was not observed in 5-year all-cause death and ACS in multivariable Cox regression analysis. After controlling variables, age, body mass index, hemoglobin value and LVEF were associated with the clinical outcomes in both genders. CONCLUSION: Gender difference was not observed in the long-term all-cause death and ACS in patients following PCI. PMID- 26896724 TI - The time course of conflict on the Cognitive Reflection Test. AB - Reasoning that is deliberative and reflective often requires the inhibition of intuitive responses. The Cognitive Reflection Test (CRT) is designed to assess people's ability to suppress incorrect heuristic responses in favour of deliberation. Correct responding on the CRT predicts performance on a range of tasks in which intuitive processes lead to incorrect responses, suggesting indirectly that CRT performance is related to cognitive control. Yet little is known about the cognitive processes underlying performance on the CRT. In the current research, we employed a novel mouse tracking methodology to capture the time-course of reasoning on the CRT. Analysis of mouse cursor trajectories revealed that participants were initially drawn towards the incorrect (i.e., intuitive) option even when the correct (deliberative) option was ultimately chosen. Conversely, participants were not attracted to the correct option when they ultimately chose the incorrect intuitive one. We conclude that intuitive processes are activated automatically on the CRT and must be inhibited in order to respond correctly. When participants responded intuitively, there was no evidence that deliberative reasoning had become engaged. PMID- 26896725 TI - A bilingual disadvantage in metacognitive processing. AB - Recent research indicating that bilingualism is associated with enhanced executive function suggests that this enhancement may operate within a broader spectrum of cognitive abilities than previously thought (e.g., Stocco & Prat, 2014). In this study, we focus on metacognition or the ability to evaluate one's own cognitive performance (Flavell, 1979). Over the course of two experiments, we presented young healthy adult monolinguals and bilinguals with a perceptual two alternative-forced-choice task followed by confidence judgements. Results from both experiments indicated that bilingual participants showed a disadvantage in metacognitive efficiency, determined through the calculation of Mratio (Maniscalco & Lau, 2014). Our findings provide novel insight into the potential differences in bilingual and monolingual cognition, which may indicate a bilingual disadvantage. Results are discussed with reference to the balance of advantages versus disadvantages associated with multilanguage learning. PMID- 26896726 TI - Interference effects of categorization on decision making. AB - Many decision making tasks in life involve a categorization process, but the effects of categorization on subsequent decision making has rarely been studied. This issue was explored in three experiments (N=721), in which participants were shown a face stimulus on each trial and performed variations of categorization decision tasks. On C-D trials, they categorized the stimulus and then made an action decision; on X-D trials, they were told the category and then made an action decision; on D-alone trials, they only made an action decision. An interference effect emerged in some of the conditions, such that the probability of an action on the D-alone trials (i.e., when there was no explicit categorization before the decision) differed from the total probability of the same action on the C-D or X-D trials (i.e., when there was explicit categorization before the decision). Interference effects are important because they indicate a violation of the classical law of total probability, which is assumed by many cognitive models. Across all three experiments, a complex pattern of interference effects systematically occurred for different types of stimuli and for different types of categorization-decision tasks. These interference effects present a challenge for traditional cognitive models, such as Markov and signal detection models, but a quantum cognition model, called the belief-action entanglement (BAE) model, predicted that these results could occur. The BAE model employs the quantum principles of superposition and entanglement to explain the psychological mechanisms underlying the puzzling interference effects. The model can be applied to many important and practical categorization-decision situations in life. PMID- 26896727 TI - Evaluation of structure, chaperone-like activity and protective ability of peroxynitrite modified human alpha-Crystallin subunits against copper-mediated ascorbic acid oxidation. AB - The copper-catalyzed oxidation of ascorbic acid (ASA) to dehydroascorbate (DHA) and hydrogen peroxide plays a central role in pathology of cataract diseases during ageing and in diabetic patients. In the current study, the structural feature, chaperone-like activity and protective ability of peroxynitrite (PON) modified alphaA- and alphaB-Crystallin (Cry) against copper-mediated ASA oxidation were studied using different spectroscopic measurements and gel mobility shift assay. Upon PON modification, additional to protein structural alteration, the contents of nitrotyrosine, nitrotryptophan, dityrosine and carbonyl groups were significantly increased. Moreover, alphaB-Cry demonstrates significantly larger capacity for PON modification than alphaA-Cry. Also, based on the extent of PON modification, these proteins may display an improved chaperone-like activity and enhanced protective ability against copper-mediated ASA oxidation. In the presence of copper ions, chaperone-like activity of both native and PON-modified alpha-Cry subunits were appreciably improved. Additionally, binding of copper ions to native and PON-modified proteins results in the significant reduction of their solvent exposed hydrophobic patches. Overall, the increase in chaperone-like activity/ASA protective ability of PON modified alpha-Cry and additional enhancement of its chaperoning action with copper ions appear to be an important defense mechanism offered by this protein. PMID- 26896728 TI - Temperature, pH and redox responsive cellulose based hydrogels for protein delivery. AB - Cellulose based hydrogels are important due to their biocompatibility, non toxicity and natural origin. In this work, a new set of pH, temperature and redox responsive hydrogels were prepared from carboxymethylcellulose (CMC) and poly(N isopropylacrylamide). Copolymeric (CP) hydrogels were synthesized by copolymerizing N-isopropylacrylamide (NIPA) and methacrylated carboxymethylcellulose, semi-interpenetrating network (SIPN) hydrogels were prepared by polymerizing NIPA in presence of CMC. Two types of cross-linkers were used viz. N,N'-methylenebisacrylamide (BIS) and N,N'-bis(acryloyl)cystamine (CBA), a redox sensitive cross-linker. The structures of the hydrogels were characterized by FTIR and SEM studies. The CP hydrogels were found to be more porous than corresponding SIPNs which resulted in higher swelling for the CP hydrogels. Swelling for both the hydrogels were found to increase with CMC content. While the swelling of SIPN hydrogels showed discontinuous temperature dependency, CP hydrogels showed gradual decrease in water retention values with increase in temperature. CBA cross-linked hydrogels showed higher swelling in comparison to BIS cross-linked hydrogels. Additionally, lysozyme was loaded in the hydrogels and its in vitro release was studied in various pH, temperature and in presence of a reducing agent, glutathione (GSH). The release rate was found to be maximum at lower temperature, lower pH and in presence of GSH. PMID- 26896729 TI - Phosphatidic acid induces EHD3-containing membrane tubulation and is required for receptor recycling. AB - EHD3 is localized on the tubular structures of early endosomes, and it regulates their trafficking pathway. However, the regulatory mechanism of EHD3-containing tubular structures remains poorly understood. An in vitro liposome co sedimentation assay revealed that EHD3 interacted with phosphatidic acid through its helical domain and this interaction induced liposomal tubulations. Additionally, inhibiting phosphatidic acid synthesis with diacylglycerol kinase inhibitor or lysophosphatidic acid acyltransferase inhibitor significantly reduced the number of EHD3-containing tubules and impaired their trafficking from early endosomes. These results suggest that EHD3 and phosphatidic acid cooperatively regulate membrane deformation and trafficking from early endosomes. PMID- 26896730 TI - Are there perceptual differences to varying levels of blood flow restriction? AB - The application of blood flow restriction (BFR) with low load exercise has been shown to produce favorable muscle and vascular adaptations. Given the potential clinical utility of BFR, it is important to characterize the ratings of perceived exertion (RPE) and discomfort across a variety of relative pressures as the individual's perceptual response may ultimately dictate whether a participant continues with this modality of exercise. Fourteen participants completed 3 days of exercise. Conditions included unilateral elbow flexion with six pressures ranging from 40% to 90% arterial occlusion at 30% of their one repetition maximum (1RM). Differences in RPE (6: no exertion at all, 20: maximal exertion) were found across conditions for set 2 (range of 13-15), 3 (range of 15-16), and 4 (range of 15-17). Following Bonferroni adjustments, none were significant. Differences in discomfort (0: no discomfort at all; 10: maximum discomfort) were found across conditions for set 1 (range of 2-3), 2 (range of 3.2-5), 3 (range of 4-6.5), and 4 (range of 5-7). Post-hoc analyses only found differences within set 3. Although it is presently unknown if higher pressures are required for optimal adaption of tissues other than skeletal muscle, our results suggest that the perceptual rating during exercise is unlikely to be a limiting factor in the application of higher pressures. PMID- 26896731 TI - The behavior of an opponent alters pacing decisions in 4-km cycling time trials. AB - INTRODUCTION: The present study aimed to explore how athletes respond to different behaviors of their opponents. METHODS: Twelve moderately to highly physically active participants with at least two years of cycling experience completed four 4-km time trials on a Velotron cycle ergometer. After a familiarization time trial (FAM), participants performed three experimental time trials in randomized order with no opponent (NO), a virtual opponent who started slower and finished faster compared to FAM (OP-SLOWFAST), or a virtual opponent who started faster and finished slower compared to FAM (OP-FASTSLOW). Repeated measures ANOVAs (P<0.05) were used to examine differences in pacing and performance related to power output, velocity and RPE. RESULTS: OP-SLOWFAST and OP-FASTSLOW were completed faster compared to NO (385.5+/-27.5, 385.0+/-28.6, and 390.6+/-29.3s, respectively). An interaction effect for condition*distance (F=3.944, P<0.001) indicated differences in pacing profiles between conditions. Post-hoc analysis revealed that a less aggressive starting strategy was adopted in NO compared to OP-FASTSLOW and OP-SLOWFAST during the initial 1000m. Finally, a faster starting opponent evokes higher power outputs by the participants in the initial 750m compared to a slower starting opponent. CONCLUSION: The present study is the first to show that the behavior of an opponent affects pacing related decisions in laboratory-controlled conditions. Our findings support the recently proposed interdependence of perception and action, and emphasize the interaction with the environment as an important determinant for an athlete's pacing decisions, especially during the initial stages of a race. PMID- 26896732 TI - Probucol Improves Erectile Function by Restoring Endothelial Function and Preventing Cavernous Fibrosis in Streptozotocin-induced Diabetic Rats. AB - OBJECTIVE: To investigate the effects of probucol on erectile function in streptozotocin-induced diabetic rats and explore the underlying mechanisms. METHODS: A total of thirty 12-week-old Sprague-Dawley male rats received a 1-time intraperitoneal streptozotocin (60 mg/kg) or vehicle injection after a 12-hour fast. Three days later, the streptozotocin-induced diabetic rats were randomly divided into 2 groups and were treated with daily gavage feedings of probucol at doses of 0 and 500 mg/kg for 12 weeks. A positive control group underwent intraperitoneal injection of saline followed by daily gavage of saline solution. Erectile function was assessed by electrical stimulation of the cavernous nerves with real-time intracavernous pressure measurement. After euthanasia, penile tissue was investigated using immunohistochemistry, Western blot, and ELISA to assess the protein arginine-N-methyltransferase 1/dimethylarginine dimethylaminohydrolase/asymmetric dimethylarginine/nitric oxide synthase metabolism pathway. Superoxide dismutase activity and malondialdehyde levels were detected by colorimetry. We also evaluated penile histological changes such as smooth muscle contents and Masson's trichrome stain. RESULTS: Significant recovery of erectile function was observed in the probucol-treated rats than the untreated diabetic rats. The protein expression of dimethylarginine dimethylaminohydrolase and nitric oxide synthase, cyclic guanosine monophosphate concentrations, and superoxide dismutase activity in cavernous tissue of probucol treated rats were significantly higher than the untreated diabetic rats. The protein expression of protein arginine-N-methyltransferase 1, asymmetric dimethylarginine concentrations, and malondialdehyde levels in cavernous tissue of probucol-treated rats were significantly lower than the untreated diabetic rats. In addition, probucol treatment markedly augments the cavernous smooth muscle content. CONCLUSION: Probucol treatment improves erectile function by restoring endothelial function and preventing cavernous fibrosis in streptozotocin-induced diabetic rats. PMID- 26896733 TI - Predictive Factors for Reclassification and Relapse in Prostate Cancer Eligible for Active Surveillance: A Systematic Review and Meta-analysis. AB - OBJECTIVE: To systematically evaluate the evidence on the predictors of the upgrading and biochemical recurrence of prostate cancer (PC) in those patients with low-risk disease assigned to active surveillance (AS). MATERIALS AND METHODS: An electronic search of the PubMed, SCOPUS, Web of Science, CINAHL, Cochrane Library, Google Scholar, and Embase databases was performed for all reports that included detailed results of multivariate analyses of the predictors of PC reclassification and biochemical relapse during AS. Cumulative analyses of available hazard ratios (HRs) and their corresponding 95% confidence intervals were conducted using the RevMan 5.3 software to assess the potential predictors of PC upgrading and recurrence. Both random-effect model meta-analysis and Hartung-Knapp-Sidik-Jonkman meta-analysis method were applied to obtain the pooled HR for each covariate. RESULTS: In the 32 articles analyzed, encompassing about 24,236 patients with early-stage PC, the 3 clinicopathological variables significantly associated with histological progression during AS were: prostate specific antigen-density (HR 2.46; P = .0001); 2 positive cores (HR 1.54; P = .006); and race (HR 2; P = .04). Age, prostate-specific antigen levels, and suspicion on magnetic resonance imaging were not significantly associated with increased risk of progression of PC. CONCLUSION: We identified 3 strong predictors for the upgrading of PC during AS. These should be systematically evaluated to enable patients with low-risk disease to be treated with AS. PMID- 26896736 TI - Salinomycin suppresses TGF-beta1-induced epithelial-to-mesenchymal transition in MCF-7 human breast cancer cells. AB - Epithelial-to-mesenchymal transition (EMT) is the major cause of breast cancer to initiate invasion and metastasis. Salinomycin (Sal) has been found as an effective chemical compound to kill breast cancer stem cells. However, the effect of Sal on invasion and metastasis of breast cancer is unclear. In the present study, we showed that Sal reversed transforming growth factor-beta1 (TGF-beta1) induced invasion and metastasis accompanied with down-regulation of MMP-2 by experiments on human breast cancer cell line MCF-7. Sal was able to inhibit TGF beta1-induced EMT phenotypic transition and the activation of key signaling molecules involved in Smad (p-Smad2/3,Snail1) and non-Smad (beta-catenin, p-p38 MAPK) signals which cooperatively regulate the induction of EMT. Importantly, in a series of breast cancer specimens, we found strong correlation among E-cadherin expression, beta-catenin expression, and the lymph node metastatic potential of breast cancer. Our research suggests that Sal is promised to be a chemotherapeutic drug by suppressing the metastasis of breast cancer. PMID- 26896735 TI - Esophageal Expression of Active IkappaB Kinase-beta in Mice Up-Regulates Tumor Necrosis Factor and Granulocyte-Macrophage Colony-Stimulating Factor, Promoting Inflammation and Angiogenesis. AB - BACKGROUND & AIMS: IkappaB kinase-beta (IKKbeta) mediates activation of the nuclear factor-kappaB, which regulates immune and inflammatory responses. Although nuclear factor-kappaB is activated in cells from patients with inflammatory diseases or cancer, little is known about its roles in the development and progression of esophageal diseases. We investigated whether mice that express an activated form of IKKbeta in the esophageal epithelia develop esophageal disorders. METHODS: We generated ED-L2-Cre/Rosa26-IKK2caSFL mice, in which the ED-L2 promoter activates expression of Cre in the esophageal epithelia, leading to expression of a constitutively active form of IKKbeta (IKKbetaca) in epithelial cells but not in inflammatory cells or the surrounding stroma (IKKbetaca mice). Mice lacking the Cre transgene served as controls. Some mice were given intraperitoneal injections of neutralizing antibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF) or tumor necrosis factor (TNF), or immunoglobulin G1 (control), starting at 1 month of age. Epithelial tissues were collected and analyzed by immunofluorescence, immunohistochemical, and quantitative real-time polymerase chain reaction assays. Transgenes were overexpressed from retroviral vectors in primary human keratinocytes. RESULTS: IKKbetaca mice developed esophagitis and had increased numbers of blood vessels in the esophageal stroma, compared with controls. Esophageal tissues from IKKbetaca mice had increased levels of GM-CSF. Expression of IKKbetaca in primary human esophageal keratinocytes led to 11-fold overexpression of GM-CSF and 200-fold overexpression of TNF. Incubation of human umbilical vein endothelial cells with conditioned media from these keratinocytes increased endothelial cell migration by 42% and promoted formation of capillary tubes; these effects were blocked by a neutralizing antibody against GM-CSF. Injections of anti-GM-CSF reduced angiogenesis and numbers of CD31+ blood vessels in esophageal tissues of IKKbetaca mice, but did not alter the esophageal vasculature of control mice and did not alter recruitment of intraepithelial leukocytes to esophageal tissues of IKKbetaca mice. Injections of anti-TNF prevented the development of esophagitis in IKKbetaca mice. CONCLUSIONS: Constitutive activation of IKKbeta in the esophageal epithelia of mice leads to inflammation and angiogenesis, mediated by TNF and GM-CSF, respectively. PMID- 26896734 TI - Terlipressin Plus Albumin Is More Effective Than Albumin Alone in Improving Renal Function in Patients With Cirrhosis and Hepatorenal Syndrome Type 1. AB - BACKGROUND & AIMS: Hepatorenal syndrome type 1 (HRS-1) in patients with cirrhosis and ascites is a functional, potentially reversible, form of acute kidney injury characterized by rapid (<2 wk) and progressive deterioration of renal function. Terlipressin is a synthetic vasopressin analogue that acts, via vascular vasopressin V1 receptors, as a systemic vasoconstrictor. We performed a phase 3 study to evaluate the efficacy and safety of intravenous terlipressin plus albumin vs placebo plus albumin in patients with HRS-1. METHODS: Adult patients with cirrhosis, ascites, and HRS-1 (based on the 2007 International Club of Ascites criteria of rapidly deteriorating renal function) were assigned randomly to groups given intravenous terlipressin (1 mg, n = 97) or placebo (n = 99) every 6 hours with concomitant albumin. Treatment continued through day 14 unless the following occurred: confirmed HRS reversal (CHRSR, defined as 2 serum creatinine [SCr] values <=1.5 mg/dL, at least 40 hours apart, on treatment without renal replacement therapy or liver transplantation) or SCr at or above baseline on day 4. The primary end point was the percentage of patients with confirmed CHRSR. Secondary end points included the incidence of HRS reversal (defined as at least 1 SCr value <=1.5 mg/dL while on treatment), transplant-free survival, and overall survival. The study was performed at 50 investigational sites in the United States and 2 in Canada, from October 2010 through February 2013. RESULTS: Baseline demographic/clinical characteristics were similar between groups. CHRSR was observed in 19 of 97 patients (19.6%) receiving terlipressin vs 13 of 99 patients (13.1%) receiving placebo (P = .22). HRS reversal was achieved in 23 of 97 (23.7%) patients receiving terlipressin vs 15 of 99 (15.2%) receiving placebo (P = .13). SCr decreased by 1.1 mg/dL in patients receiving terlipressin and by only 0.6 mg/dL in patients receiving placebo (P < .001). Decreases in SCr and survival were correlated (r(2) = .882; P < .001). Transplant-free and overall survival were similar between groups. A significantly greater proportion of patients with CHRSR who received terlipressin survived until day 90 than patients who did not have CHRSR after receiving terlipressin (P < .001); this difference was not observed in patients who did vs did not have CHRSR after receiving placebo (P = .28). There were similar numbers of adverse events in each group, but patients in the terlipressin group had more ischemic events. CONCLUSIONS: Terlipressin plus albumin was associated with greater improvement in renal function vs albumin alone in patients with cirrhosis and HRS-1. Patients had similar rates of HRS reversal with terlipressin as they did with albumin. ClinicalTrials.gov no: NCT01143246. PMID- 26896737 TI - Stepwise pH-responsive nanoparticles containing charge-reversible pullulan-based shells and poly(beta-amino ester)/poly(lactic-co-glycolic acid) cores as carriers of anticancer drugs for combination therapy on hepatocellular carcinoma. AB - Stepwise pH-responsive nanoparticle system containing charge reversible pullulan based (CAPL) shell and poly(beta-amino ester) (PBAE)/poly(lactic-co-glycolic acid) (PLAG) core is designed to be used as carriers of paclitaxel (PTX) and combretastatin A4 (CA4) for combining antiangiogenesis and chemotherapy to treat hepatocellular carcinoma (HCC). CAPL-coated PBAE/PLGA (CAPL/PBAE/PLGA) nanoparticles displayed step-by-step responses to weakly acidic tumor microenvironment (pH ~6.5) and endo/lysosome (pH ~5.5) respectively through the cleavage of beta-carboxylic amide bond in CAPL and the "proton-sponge" effect of PBAE, thus realized the efficient and orderly releases of CA4 and PTX. In human HCC HepG2 cells and human umbilical vein endothelial cells, CAPL/PBAE/PLGA nanoparticles significantly enhanced synergistic effects of PTX and CA4 on cell proliferation and cell migration. In HepG2 tumor-bearing mice, CAPL/PBAE/PLGA nanoparticles showed excellent tumor-targeting capability and remarkably increased inhibitory effects of PTX and CA4 on tumor growth and angiogenesis. In conclusion, this novel nanoparticle system is a promising candidate as carrier for drugs against HCC. PMID- 26896739 TI - Synchrotron X-ray diffraction and scanning electron microscopy to understand enamel affected by metabolic disorder mucopolysaccharidosis. AB - Mucopolysaccharidosis (MPS) is an inherited metabolic disorder that can affect the tooth structure leading to defects. Synchrotron X-ray diffraction being a state of the art technique has been used to determine the enamel crystallite orientation in deciduous enamel affected by Mucopolysaccharidosis Type I and Mucopolysaccharidosis Type IVA and comparing these with that of healthy deciduous enamel. Using this technique it was observed that there is a loss of texture in deciduous enamel affected by Mucopolysaccharidosis Type I and Mucopolysaccharidosis Type IVA when compared to the healthy deciduous enamel. Generally it was observed that the incisal surface of the deciduous teeth possessed a higher texture or preferred orientation of enamel crystallites and on progression towards the cervical region there was a decrease in the texture or preferred orientation of enamel crystallites. Scanning electron microscopy showed that the presence of a poorly calcified layer between the enamel and dentine at the enamel-dentine junction (EDJ) in MPS affected samples was likely to be responsible for rendering the tooth structure weak and prone to fracture as is often the case in MPS affected deciduous enamel. PMID- 26896738 TI - Probing the role of chemical enhancers in facilitating drug release from patches: Mechanistic insights based on FT-IR spectroscopy, molecular modeling and thermal analysis. AB - In patches, a drug must release from patches prior to its percutaneous absorption. Chemical enhancers have been used for several decades, but their roles in drug release from patches are poorly understood. In this work, the roles of chemical enhancers in bisoprolol tartrate (BSP-T) release from patches were probed in vitro and in vivo. More importantly, an innovative mechanism insight of chemical enhancers in drug release process was provided at molecular level. FT-IR spectroscopy and molecular modeling were employed to investigate the influence of chemical enhancers on drug-adhesive interaction. The results showed chemical enhancers like Span 80, which had a strong ability forming hydrogen bonds, could decrease drug-adhesive interaction leading to the release of drug from adhesive of patches. Thermal analysis was conducted to research the influence of chemical enhancers on the thermodynamic properties of patch system. It showed that chemical enhancers promoted the formation of free volume of adhesive, which facilitated drug release process. By contrast, the influence on the thermodynamic properties of BSP-T was less effective in influencing BSP-T release process. In conclusion, chemical enhancers played an important role in facilitating BSP-T release from the adhesive DURO-TAK(r) 87-2287 of patches by decreasing drug adhesive interaction and promoting the formation of free volume of adhesive. This work may be an important step in understanding the important roles of chemical enhancers in drug release process. PMID- 26896740 TI - The fatality and morbidity components of the value of statistical life. AB - The fatality risk-money tradeoff that is the value of a statistical life (VSL) may vary with the nature of the fatality event. While all fatalities involve loss of future life expectancy, the morbidity effects and their duration may differ. This article analyzes fatality risks accompanied by morbidity effects of different duration to disentangle the mortality and morbidity components of VSL using data from the Census of Fatal Occupational Injuries (CFOI). The VSL is comprised of the sum of the value of the fatality risk and the value of the morbidity risk. Labor market valuations of morbidity risks are positive, even for fatalities that are caused by traumatic injuries. The value of the fatality risk is the dominant component of VSL, rather than the value of the morbidity risk. PMID- 26896741 TI - p11 mediates the BDNF-protective effects in dendritic outgrowth and spine formation in B27-deprived primary hippocampal cells. AB - BACKGROUND: p11 (S100A10) is a key regulator of depression-like behaviors and antidepressant drug response in rodent models. Recent studies suggest that p11 mediates the behavioral antidepressant action of brain-derived neurotrophic factor (BDNF) in rodents. BDNF improves neural plasticity, which is linked to the cellular actions of antidepressant drugs. In the present study, we investigated whether p11 regulated BDNF action on neural plasticity in vitro. METHODS: We generated primary hippocampal cultures. p11 expression, total dendritic length, and spine density were investigated under toxic conditions induced by B27 deprivation, which causes hippocampal cell death. RESULTS: B27 deprivation significantly decreased p11 expression. Treatment with BDNF significantly prevented the B27 deprivation-induced decrease in p11 levels in a concentration dependent manner, whereas these concentrations had no effect on control cultures. B27 deprivation significantly reduced the total length of hippocampal dendrites and spine density. BDNF increased the total dendritic length and spine density in conditions with or without B27. Furthermore, p11 knockdown through small interfering RNA (siRNA) transfection blocked these effects. The overexpression of p11 in B27-deprived cells increased the total dendritic length and spine density, and treatment with BDNF potentiated these effects. LIMITATION: This study should be confirmed in animal models of depression. CONCLUSION: Taken together, our data suggest that BDNF-induced improvement in neural plasticity may depend on the regulation of p11 in hippocampal cells with B27 deprivation. These results provide evidence to strengthen the theoretical basis of a role for p11 in BDNF induced antidepressant action. PMID- 26896743 TI - Successful resection of oesophageal adenocarcinoma 16 years after heart transplantation-a case report. AB - INTRODUCTION: With improving results of heart transplantation and subsequently increasing survival, long-term complications such as neoplastic malignancies are more often being discovered. PRESENTATION OF CASE: In this report, we present a unique case of successful oesophagus resection with gastric pull-up, on a heart transplanted patient diagnosed with oesophageal adenocarcinoma. DISCUSSION: With the growing number of long-term surviving heart transplanted patients, the number of neoplasia in this patient-group will subsequently grow. Since physical condition and quality of life in long-term surviving heart transplanted patients is comparable to the general population, and since surgical treatment remains the mainstay of treatment for localised oesophageal carcinoma in non-heart transplanted patients, a larger subgroup of heart transplanted patients will most likely be considered for cancer surgery. CONCLUSION: Our case demonstrates the possibility of operating on the heart transplanted patient-group, and supports the option, that well-managed heart transplantation not should be a limiting factor, when deciding whether a patient is a candidate for surgical intervention or not. PMID- 26896742 TI - Impact of 5-HTTLPR on SSRI serotonin transporter blockade during emotion regulation: A preliminary fMRI study. AB - BACKGROUND: The short ('S') allele of the serotonin transporter (5-HTT)-linked polymorphic region (5-HTTLPR) is associated with increased negative emotion processing bias, and this polymorphism moderates acute effects of selective serotonin reuptake inhibitor (SSRI) treatment. In this preliminary study, we explore the moderating effect of 5-HTTLPR on the impact of the SSRI, escitalopram during emotion regulation of negative emotional stimuli. METHOD: Thirty-six healthy Caucasian, female participants underwent two fMRI scanning sessions following single dose escitalopram and placebo administration separated by a seven-day washout period according to a double-blind, randomized, placebo controlled crossover design. Functional connectivity analysis was employed with a left (L) amygdala seed and a right interior frontal gyrus (R IFG) target. RESULTS: Changes in functional connectivity with emotion regulation and treatment were linearly related to 5-HTTLPR 'L' allele load such that negative R IFG-L amygdala connectivity was increased with an increasing number of 'L' alleles. Therefore, escitalopram may facilitate the effects of reappraisal by enhancing negative functional connectivity, a finding that is greatest in participants homozygous for the 'L' allele and least in those homozygous for the 'S' allele. LIMITATIONS: Sub-samples of the homozygote 'S/S' and 'L/L' 5-HTTLPR groupings were small. However, the within-subjects nature of the experiment and observing changes at the individual subject level increases our confidence in the findings of the present study. CONCLUSIONS: The present study elucidates a potential neural mechanism by which antidepressant treatment produces differential treatment outcomes dependent on the 5-HTTLPR polymorphism, providing new and important leads for models of antidepressant action. PMID- 26896744 TI - Genotypic and antimicrobial characterization of pathogenic bacteria at different stages of cattle slaughtering in southern Brazil. AB - Meat can be contaminated in different stages of the slaughtering process and the identification of these stages is the starting point to implement adequate control measures. The objectives of this study were to assess the presence of pathogenic microorganisms in cattle carcasses, to identify the most important contamination points of the slaughtering process, and to evaluate the possible risk factors related to them in a cattle slaughterhouse. To this aim, 108 cattle carcasses were sampled at three stages of the slaughtering process: Point 1 (hides after bleeding); Point 2 (carcasses after hide removal); and Point 3 (carcasses immediately after division). Escherichia coli O157:H7, Listeria monocytogenes and Salmonella Livingstone were isolated from the carcasses. Phenotypic and genotypic characterization indicated that there was cross contamination among animals, since bacteria with identical genotypic and phenotypic profiles were isolated from different animals at the same sampling day. Furthermore, this is the first report about the isolation of E. coli O157:H7 in a bovine slaughterhouse from southern Brazil. PMID- 26896745 TI - Osteoprotegerin: A novel biomarker for inflammatory bowel disease and gastrointestinal carcinoma. AB - Osteoprotegerin (OPG) is a member of the tumor necrosis factor receptor superfamily of proteins. Although initial data illustrated the key role that OPG plays in bone turnover, numerous recent reports indicate that OPG is also an important factor in inflammatory pathways and tumor cell survival. OPG contributes directly to inflammatory processes and has been evaluated as a novel non-invasive biomarker of gut inflammation. Furthermore, OPG affects cell turn over, differentiation, death, and survival via extracellular pathways, correlating with worse prognosis in inflammatory bowel diseases and several gastrointestinal carcinomas. It is now clear that OPG has multiple functions and characteristics. This review gives an overview of OPG, highlights its roles in different extracellular pathways, and outlines how OPG could be used as a novel non-invasive biological marker in inflammatory bowel diseases and gastrointestinal carcinomas. PMID- 26896746 TI - Transcriptional repressor DREAM regulates trigeminal noxious perception. AB - Expression of the downstream regulatory element antagonist modulator (DREAM) protein in dorsal root ganglia and spinal cord is related to endogenous control mechanisms of acute and chronic pain. In primary sensory trigeminal neurons, high levels of endogenous DREAM protein are preferentially localized in the nucleus, suggesting a major transcriptional role. Here, we show that transgenic mice expressing a dominant active mutant of DREAM in trigeminal neurons show increased responses following orofacial sensory stimulation, which correlates with a decreased expression of prodynorphin and brain-derived neurotrophic factor in trigeminal ganglia. Genome-wide analysis of trigeminal neurons in daDREAM transgenic mice identified cathepsin L and the monoglyceride lipase as two new DREAM transcriptional targets related to pain. Our results suggest a role for DREAM in the regulation of trigeminal nociception. This article is part of the special article series "Pain". PMID- 26896747 TI - It is rocket science - why dietary nitrate is hard to 'beet'! Part I: twists and turns in the realization of the nitrate-nitrite-NO pathway. AB - Dietary nitrate (found in green leafy vegetables, such as rocket, and in beetroot) is now recognized to be an important source of nitric oxide (NO), via the nitrate-nitrite-NO pathway. Dietary nitrate confers several cardiovascular beneficial effects on blood pressure, platelets, endothelial function, mitochondrial efficiency and exercise. While this pathway may now seem obvious, its realization followed a rather tortuous course over two decades. Early steps included the discovery that nitrite was a source of NO in the ischaemic heart but this appeared to have deleterious effects. In addition, nitrate-derived nitrite provided a gastric source of NO. However, residual nitrite was not thought to be absorbed systemically. Nitrite was also considered to be physiologically inert but potentially carcinogenic, through N-nitrosamine formation. In Part 1 of a two part Review on the nitrate-nitrite-NO pathway we describe key twists and turns in the elucidation of the pathway and the underlying mechanisms. This provides the critical foundation for the more recent developments in the nitrate-nitrite-NO pathway which are covered in Part 2. PMID- 26896750 TI - Effect of Exercise Training on Fitness in Multiple Sclerosis: A Meta-Analysis. AB - OBJECTIVE: To provide a quantitative synthesis of randomized controlled trials (RCTs) examining the effect of exercise training on muscular and cardiorespiratory fitness in persons with multiple sclerosis (MS). DATA SOURCES: Three electronic databases, PubMed, Google Scholar, and Web of Science, were searched for all relevant articles published up until October 2014. STUDY SELECTION: Keywords included exercise or aerobic or strength or resistance training or cardiorespiratory and multiple sclerosis. Trials examining the effect of exercise training on muscular and/or cardiorespiratory fitness parameters were included. DATA EXTRACTION: The initial search yielded 1501 articles; of these, 62 were reviewed in detail, and 20 RCTs met the inclusion criteria and provided enough data to compute effect sizes (ESs) (Cohen d). The meta-analyses was conducted using a random effects model to compute the overall or mean ES per fitness parameter. DATA SYNTHESIS: The mean ES was .27 (SE=.05; 95% confidence interval [CI], .17-.38; z=5.05; P<.001) for muscular fitness outcomes and .47 (SE=.09; 95% CI, .30-.65; z=5.4; P<.001) for cardiorespiratory fitness outcomes. The weighted mean ES was not heterogeneous for muscular (Q13=11.09, P=.60, I(2)=.00) or cardiorespiratory (Q9=7.83, P=.55, I(2)=.00) fitness outcomes. CONCLUSIONS: The cumulative evidence supports that exercise training is associated with changes in muscular (small in magnitude) and cardiorespiratory (moderate in magnitude) fitness outcomes in persons with MS. Such an indication of magnitude is important for clinical research and practice by providing an evidence-based estimate of the actual benefit that exercise training confers on physiological fitness. PMID- 26896748 TI - High glucose-induced oxidative stress represses sirtuin deacetylase expression and increases histone acetylation leading to neural tube defects. AB - Aberrant epigenetic modifications are implicated in maternal diabetes-induced neural tube defects (NTDs). Because cellular stress plays a causal role in diabetic embryopathy, we investigated the possible role of the stress-resistant sirtuin (SIRT) family histone deacetylases. Among the seven sirtuins (SIRT1-7), pre-gestational maternal diabetes in vivo or high glucose in vitro significantly reduced the expression of SIRT 2 and SIRT6 in the embryo or neural stem cells, respectively. The down-regulation of SIRT2 and SIRT6 was reversed by superoxide dismutase 1 (SOD1) over-expression in the in vivo mouse model of diabetic embryopathy and the SOD mimetic, tempol and cell permeable SOD, PEGSOD in neural stem cell cultures. 2,3-dimethoxy-1,4-naphthoquinone (DMNQ), a superoxide generating agent, mimicked high glucose-suppressed SIRT2 and SIRT6 expression. The acetylation of histone 3 at lysine residues 56 (H3K56), H3K14, H3K9, and H3K27, putative substrates of SIRT2 and SIRT6, was increased by maternal diabetes in vivo or high glucose in vitro, and these increases were blocked by SOD1 over expression or tempol treatment. SIRT2 or SIRT6 over-expression abrogated high glucose-suppressed SIRT2 or SIRT6 expression, and prevented the increase in acetylation of their histone substrates. The potent sirtuin activator (SRT1720) blocked high glucose-increased histone acetylation and NTD formation, whereas the combination of a pharmacological SIRT2 inhibitor and a pan SIRT inhibitor mimicked the effect of high glucose on increased histone acetylation and NTD induction. Thus, diabetes in vivo or high glucose in vitro suppresses SIRT2 and SIRT6 expression through oxidative stress, and sirtuin down-regulation-induced histone acetylation may be involved in diabetes-induced NTDs. The mechanism underlying pre-gestational diabetes-induced neural tube defects (NTDs) is still elusive. Our study unravels a new epigenetic mechanism in which maternal diabetes induced oxidative stress represses sirtuin deacetylase 2 (SIRT2) and 6 (SIRT6) expression leading to histone acetylation and gene expression. SIRT down regulation mediates the teratogenicity of diabetes leading to (NTD) formation. The study provides a mechanistic basis for the development of natural antioxidants and SIRT activators as therapeutics for diabetic embryopathy. PMID- 26896749 TI - Oral treatment with zinc sulfate increases the expression of Th1 cytokines mRNA in BALB/c mice infected with Leishmania major. AB - Leishmaniases consist of a group of diseases caused by protozoan parasites of Leishmania genus. The outcome of the disease depends on the immune responses of the host as well as the pathogenicity of the strain of the parasite. In murine models, the inoculation of Leishmania major into resistant mice results in Th1 responses and recovery from the infection. However in the susceptible mice, the same inoculation leads to a profile of Th2 responses. Zinc (Zn) is an essential trace element which is required for the growth and development of the immune responses. In this study, the influence of Zn sulfate on mRNA expression of main cytokines of the immune response was studied in susceptible BALB/c mice infected with L. major. The inoculated mice were divided into 3 groups, namely the untreated (control), the zinc sulfate treated (weeks 2, 4 and 8), and the Glucantime-treated (weeks 4 and 8) mice. During different time points post infection, the lesion sizes and the parasite burden were measured in all the groups. Moreover, the expression of Ifng, Il4, Il10 and Il12 mRNA levels in the draining lymph nodes of the treated mice were compared to the control mice using real-time PCR. Our data demonstrated significant decreases in lesion sizes and parasite loads in Zn sulfate treated group compared to the untreated group. Moreover, significant fold increases in expression of Ifng transcript were observed in mice treated with Zn sulfate compared to the control. The ratio of Ifng/Il4 mRNA was also higher in Zn sulfate-treated mice compared to Glucantime treated animals. These results indicate that Zn Sulfate has the ability to induce strong Th1 responses in susceptible BALB/c mice inoculated with L. major. PMID- 26896751 TI - Mechanisms of BRAFi-induced hyperproliferative cutaneous conditions. PMID- 26896752 TI - Novel measurement method on plain radiographs to predict postoperative stem anteversion in cementless THA. AB - Preoperative knowledge of femoral stem anteversion can reduce instability and impingement especially using the standard "cup first" technique in cementless total hip arthroplasty (THA). In this study, we asked whether stems at risk of retroversion or high anteversion (>20 degrees ) can be detected preoperatively using hip radiographs in two planes (anteroposterior and Lauenstein). In 123 patients undergoing cementless THA using a non-anatomic, non-modular, straight stem, low centered hip radiographs in two planes were obtained preoperatively and three-dimensional computed tomography (3D-CT) 6 week postoperatively. The novel developed Isthmus Ratio (iRatio) as the relation between canal isthmus and calcar isthmus in the anteroposterior and Lauenstein view was calculated by two observers twice in a 6-week interval. iRatio was compared to postoperative 3D-CT stem version measured by an independent and blinded, external institute. We found a correlation between mean radiographic iRatio and 3D-CT stem torsion of r = 0.578 (p < 0.0001). The observers had excellent agreements within (ICC >=0.918) and between (mean CCC = 0.967) radiographic iRatio measurements. Eighty-one percent (21/26) of the retroverted cementless stems had a preoperative iRatio below 0.35 and 91% (10/11) of stems with an anteversion exceeding 20 degrees an iRatio above 0.55, respectively. The novel iRatio represents a feasible and reliable method for analyzing anteversion of the final stem on plain radiographs before cementless THA with a straight, tapered stem. iRatios below 0.35 and above 0.55 represent a warning of retroversion and anteversion more than 20 degrees of the final stem, respectively. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2025-2030, 2016. PMID- 26896753 TI - Class I PI-3-Kinase Signaling Is Critical for Bone Formation Through Regulation of SMAD1 Activity in Osteoblasts. AB - Bone formation and homeostasis is carried out by osteoblasts, whose differentiation and activity are regulated by osteogenic signaling networks. A central mediator of these inputs is the lipid kinase phosphatidylinositol 3 kinase (PI3K). However, at present, there are no data on the specific role of distinct class IA PI3K isoforms in bone biology. Here, we performed osteoblast specific deletion in mice to show that both p110alpha and p110beta isoforms are required for survival and differentiation and function of osteoblasts and thereby control bone formation and postnatal homeostasis. Impaired osteogenesis arises from increased GSK3 activity and a depletion of SMAD1 protein levels in PI3K deficient osteoblasts. Accordingly, pharmacological inhibition of GSK3 activity or ectopic expression of SMAD1 or SMAD5 normalizes bone morphogenetic protein (BMP) transduction and osteoblast differentiation. Together, these results identify the PI3K-GSK3-SMAD1 axis as a central node integrating multiple signaling networks that govern bone formation and homeostasis. (c) 2016 American Society for Bone and Mineral Research. PMID- 26896754 TI - Methamphetamine abstinence induces changes in MU-opioid receptor, oxytocin and CRF systems: Association with an anxiogenic phenotype. AB - The major challenge in treating methamphetamine addicts is the maintenance of a drug free-state since they experience negative emotional symptoms during abstinence, which may trigger relapse. The neuronal mechanisms underlying long term withdrawal and relapse are currently not well-understood. There is evidence suggesting a role of the oxytocin (OTR), MU-opioid receptor (MOPr), dopamine D2 receptor (D2R), corticotropin-releasing factor (CRF) systems and the hypothalamic pituitary-adrenal (HPA)-axis in the different stages of methamphetamine addiction. In this study, we aimed to characterize the behavioral effects of methamphetamine withdrawal in mice and to assess the modulation of the OTR, MOPr, D2R, CRF and HPA-axis following chronic methamphetamine administration and withdrawal. Ten-day methamphetamine administration (2 mg/kg) increased OTR binding in the amygdala, whilst 7 days of withdrawal induced an upregulation of this receptor in the lateral septum. Chronic methamphetamine treatment increased plasma OT levels that returned to control levels following withdrawal. In addition, methamphetamine administration and withdrawal increased striatal MOPr binding, as well as c-Fos(+)/CRF(+) neuronal expression in the amygdala, whereas an increase in plasma corticosterone levels was observed following METH administration, but not withdrawal. No differences were observed in the D2R binding following METH administration and withdrawal. The alterations in the OTR, MOPr and CRF systems occurred concomitantly with the emergence of anxiety-related symptoms and the development of psychomotor sensitization during withdrawal. Collectively, our findings indicate that chronic methamphetamine use and abstinence can induce brain-region specific neuroadaptations of the OTR, MOPr and CRF systems, which may, at least, partly explain the withdrawal-related anxiogenic effects. PMID- 26896756 TI - Prevalence and characteristics of naturally occurring sofosbuvir resistance associated variants in patients with hepatitis C virus genotype 1b infection. AB - AIM: Sofosbuvir (SOF), a nucleotide analog pro-drug, targets hepatitis C virus (HCV) NS5B polymerase and shows potential for treating HCV infection, given its high efficacy and good barrier to resistance. However, in addition to the rare resistant-associated variant (RAV) of non-structural protein NS5B S282T, several new potential RAVs of SOF have been reported, especially related to HCV genotype 1b. However, the prevalence and characteristics of these RAVs have not been clarified. METHODS: We analyzed the prevalence of variants in the NS3/NS5A/NS5B regions in 96 patients treated with simeprevir (SMV) combination therapy, and the prevalence of RAVs in patients showing treatment failure was determined by direct or deep-sequencing methods. Associations between these potential RAVs and clinical factors were also analyzed. RESULTS: Prevalence of NS5B RAV C316N was high (46.9%, 45/96), whereas that of NS5B L159F was relatively low (1.04%, 1/96); however, deep sequencing showed that 30.0% of patients with C316N also had NS5B RAV L159F. Additionally, there was no significant relationship between the existence of potential NS5B and NS5A or NS3 RAVs. However, the presence of NS5B C316N was significantly associated with an HCV core amino acid 91 substitution. No significant difference was detected between each RAV and sustained virological response in simeprevir combination therapy. CONCLUSION: We provide clear evidence of the high prevalence of two potential naturally occurring NS5B RAVs (C316N and L159F) in Japan. It may be important to pay particular attention to these new potential RAVs, especially when using SOF-based therapy in patients with RAVs due to previous direct-acting antiviral therapy failure. PMID- 26896757 TI - Arthroscopy of the Temporomandibular Joint in Patients With Juvenile Idiopathic Arthritis. AB - PURPOSE: The early diagnosis of temporomandibular joint (TMJ) involvement in patients with juvenile idiopathic arthritis (JIA) before joint destruction and growth disturbances could allow for interceptive treatment. The purpose of this article is to report early TMJ arthroscopic findings in patients with JIA. PATIENTS AND METHODS: This was a case series of 3 patients with JIA treated at the Emory University Division of Oral and Maxillofacial Surgery from July 2011 through December 2012. Patients were included if they had a confirmed diagnosis of JIA, did not respond to anti-rheumatologic medication, and had TMJ pain or limited mouth opening. All patients underwent TMJ arthroscopy with an injection of triamcinolone hexacetonide. Demographics, medical history, magnetic resonance imaging findings, arthroscopic findings, and postoperative course were reported. RESULTS: Three female patients (mean age, 12.5 yr; 5 joints) underwent arthroscopy. Arthroscopic findings consisted of mild to moderate synovitis and grade 2 to 4 chondromalacia with or without fibrosis. Postoperatively, all patients had improvement in pain and mouth opening. CONCLUSIONS: There was a positive correlation between duration of JIA activity in the TMJ and severity of arthroscopic findings. Arthroscopic lysis and lavage combined with triamcinolone hexacetonide injection resulted in improvement in pain and range of motion. PMID- 26896758 TI - High-Volume Surgeons Deliver Larger Surgical Margins in Oral Cavity Cancer. AB - PURPOSE: In oral cavity cancer surgery there are many factors that contribute to the surgical margin; thus, the factors determining patient outcomes are still not completely understood. The aim of this study was to determine which variable or variables had the greatest influence on increasing the size of the surgical margin. MATERIALS AND METHODS: A retrospective cohort study was conducted at the Royal Brisbane and Women's Hospital of patients who underwent resective surgery for a primary oral cavity cancer from January 1, 2008 through December 31, 2012. The primary outcome variable was the surgical margin, defined as the closest distance between the surgical edge and invasive cancer. A heterogeneous set of predictor variables was identified as potentially affecting the primary outcome variable: demographic, 5 surgical, and 7 histologic variables. The data then underwent statistical analysis using univariable linear regression, and variables that were found to have a statistical association were retained in a non interaction multivariable model. RESULTS: This study included 250 patients. The results showed that high-volume surgeons delivered larger surgical margins than low-volume surgeons. The single most important variable associated with larger surgical margins was who performed the resective operation. The following variables also were associated with smaller surgical margins: retromolar trigone location, non-squamous cell carcinomas, perineural invasion, and a lip-split mandibulectomy surgical approach. CONCLUSION: There was a strong association between high-volume surgeons and larger surgical margins, supporting the rationalization of oral cavity cancer management in high-volume centers and by high-volume surgeons. PMID- 26896759 TI - How Can the Complications of Central Vein Catheters Be Reduced?: From Barrier Protection to Showering: Extraluminal Prophylaxis and Management of Catheter Infections. PMID- 26896760 TI - Magnifying endoscopy simple diagnostic algorithm for early gastric cancer (MESDA G). AB - Gastric cancer is the third leading cause of cancer death worldwide. Early detection and accurate diagnosis of mucosal cancer is desirable in order to achieve decreased mortality; cause-specific survival of patients with early gastric cancer is reported to exceed 95%. Endoscopy is the functional modality to detect early cancer; however, the procedure is not definitive when using conventional white-light imaging. In contrast, magnifying narrow-band imaging (M NBI), a novel endoscopic technology, is a powerful tool for characterizing gastric mucosal lesions because it can visualize the microvascular architecture and microsurface structure. To date, many reports on the diagnosis of early gastric cancer by M-NBI, including multicenter prospective randomized studies conducted in Japan, have been published in peer-reviewed international journals. Based on these published data, we devised a proposal for a diagnostic strategy for gastric mucosal cancer using M-NBI to simplify the process of diagnosis and improve accuracy. Herein, we recommend a diagnostic algorithm for early gastric cancer using magnifying endoscopy. PMID- 26896761 TI - Long-term efficacy of endoscopic ligation plus cyanoacrylate injection with or without sclerotherapy for variceal bleeding. AB - OBJECTIVE: This study aimed to evaluate the long-term outcomes and efficacy of continued ligation plus cyanoacrylate injection compared with those of combined ligation and sclerotherapy plus cyanoacrylate injection for secondary prophylaxis of variceal bleeding in cirrhotic patients with concomitant esophageal and gastric varices. METHODS: Medical records of the patients who were admitted for variceal bleeding due to liver cirrhosis were retrospectively reviewed and their related data was collected. The patients were divided into two groups, including the continued ligation plus cyanoacrylate injection group [the sclerotherapy (-) group] and the combined ligation and sclerotherapy plus cyanoacrylate injection group [the sclerotherapy (+) group]. The Kaplan-Meier survival analysis was conducted and log-rank test was used to compare the differences between the two groups. RESULTS: Altogether 125 patients were enrolled between 1 April 2004 and 31 December 2012. After a median follow-up of 23.4 months, no significant difference was observed between the two groups in regard to variceal rebleeding (29.7% vs 47.5%, P = 0.097) and mortality (12.5% vs 14.8%, P = 0.879). Among patients with ascites the cumulative rebleeding rate was significantly lower in the sclerotherapy (-) group (26.3% vs 59.4%, P = 0.020). A relapse of bleeding after the initial endoscopic therapy was an independent prognostic factor of rebleeding (P = 0.004). Portal thrombosis was an independent prognostic factor for mortality (P = 0.044). CONCLUSION: No superiority of combined ligation and sclerotherapy compared with continued ligation and cyanoacrylate injection for secondary prophylaxis of variceal bleeding is observed. PMID- 26896755 TI - Metabotropic glutamate receptors in cancer. AB - Metabotropic glutamate receptors (mGluRs) are widely known for their roles in synaptic signaling. However, accumulating evidence suggests roles of mGluRs in human malignancies in addition to synaptic transmission. Somatic cell homeostasis presents intriguing possibilities of mGluRs and glutamate signaling as novel targets for human cancers. More recently, aberrant glutamate signaling has been shown to participate in the transformation and maintenance of various cancer types, including glioma, melanoma skin cancer, breast cancer, and prostate cancer, indicating that genes encoding mGluRs, GRMs, can function as oncogenes. Here, we provide a review on the interactions of mGluRs and their ligand, glutamate, in processes that promote the growth of tumors of neuronal and non neuronal origins. Further, we discuss the evolution of riluzole, a glutamate release inhibitor approved for amyotrophic lateral sclerosis (ALS), but now fashioned as an mGluR1 inhibitor for melanoma therapy and as a radio-sensitizer for tumors that have metastasized to the brain. With the success of riluzole, it is not far-fetched to believe that other drugs that may act directly or indirectly on other mGluRs can be beneficial for multiple applications. This article is part of the Special Issue entitled 'Metabotropic Glutamate Receptors, 5 years on'. PMID- 26896762 TI - A novel approach for biomechanical spine analysis: Mechanical response of vertebral bone augmentation by kyphoplasty to stabilise thoracolumbar burst fractures. AB - Kyphoplasty has been shown as a well-established technique for spinal injuries. This technique allows a vertebral bone augmentation with a reduction of morbidity and does not involve any adjacent segment immobilisation. There is a lack of biomechanical information resulting in major gaps of knowledge such as: the evaluation of the "quality" of stabilisation provided by kyphoplasty as a standalone procedure in case of unstable fracture. Our objective is to analyse biomechanical response of spine segments stabilised by Kyphoplasty and PMMA cement after experiencing burst fractures. Six fresh-frozen cadaveric spine specimens constituted by five vertebra (T11-L3) and four disks were tested. A specific loading setup has been developed to impose pure moments corresponding to loadings of flexion-extension, lateral bending and axial rotation. Tests were performed on each specimen in an intact state and post kyphoplasty following a burst fracture. Strain measurements and motion variations of spinal unit are measured by a 3D optical method. Strain measurements on vertebral bodies after kyphoplasty shows a great primary stabilisation. Comparisons of mobility and angles variations between the intact and post kyphoplasty states do not highlight significant difference. Percutaneous kyphoplasty offers a good primary stability in case of burst fracture. Kinematics analysis during physiological movements shows that this stabilisation solution preserve disk mobility in each adjacent spinal unit. PMID- 26896763 TI - Static and fatigue mechanical behavior of three dental CAD/CAM ceramics. AB - PURPOSE: The aim of this study was to measure the mechanical properties and fatigue behavior of three contemporary used dental ceramics, zirconia Cercon((r)) (ZC), lithium disilicate e.max((r)) CAD (LD), and polymer-infiltrated ceramic Enamic((r)) (PIC). METHODS: Flexural strength of each CAD/CAM ceramic was measured by three point bending (n=15) followed by Weibull analysis. Elastic modulus was calculated from the load-displacement curve. For cyclic fatigue loading, sinusoidal loading with a frequency of 8Hz with minimum load 3N were applied to these ceramics (n=24) using three point bending from 10(3) to 10(6) cycles. Fatigue limits of these ceramics were predicted with S-N fatigue diagram. Fracture toughness and Vickers hardness of the ceramics were measured respectively by single edge V-notch beam (SEVNB) and microindentation (Hv 0.2) methods. Chemical compositions of the materials' surfaces were analyzed by EDS, and microstructural analysis was conducted on the fracture surfaces by SEM. One way ANOVA was performed and the level of significance was set at 0.05 to analyze the numerical results. RESULTS: The mean flexural strength of ZC, LD, and PIC was respectively 886.9, 356.7, and 135.8MPa. However, the highest Weibull modulus belonged to PIC with 19.7 and the lowest was found in LD with 7.0. The fatigue limit of maximum load for one million cycles of ZC, LD, and PIC was estimated to be 500.1, 168.4, and 73.8GPa. The mean fracture toughness of ZC, LD, and PIC was found to be respectively 6.6, 2.8, and 1.4MPam(1/2), while the mean Vickers hardness was 1641.7, 676.7, and 261.7Hv. Fracture surfaces followed fatigue loading appeared to be smoother than that after monotonic loading. CONCLUSIONS: Mechanical properties of ZC were substantially superior to the two other tested ceramics, but the scattering of data was the least in PIC. The fatigue limit was found to be approximately half of the mean flexural strength for all tested ceramics. PMID- 26896764 TI - Intermediate activity of midge antifreeze protein is due to a tyrosine-rich ice binding site and atypical ice plane affinity. AB - An antifreeze protein (AFP) from a midge (Chironomidae) was recently discovered and modelled as a tightly wound disulfide-braced solenoid with a surface-exposed rank of stacked tyrosines. New isoforms of the midge AFP have been identified from RT-PCR and are fully consistent with the model. Although they differ in the number of 10-residue coils, the row of tyrosines that form the putative ice binding site is conserved. Recombinant midge AFP has been produced, and the properly folded form purified by ice affinity. This monomeric AFP has a distinct circular dichroism spectrum, a melting temperature between 35 and 50 degrees C and is fully renaturable on cooling. Mutagenesis of the middle tyrosine in the rank of seven eliminates antifreeze activity, whereas mutation of a tyrosine off this predicted ice-binding face had no such effect. This AFP has unusual properties compared to other known AFPs. First, its freezing-point depression activity is intermediate between that of the hyperactive and moderately active AFPs. As with hyperactive AFPs, when midge AFP-bound ice crystals exceed their freezing-point depression, ice grows explosively perpendicular to the c-axis. However, midge AFP does not bind to the basal plane of ice as do hyperactive AFPs, but rather to a pyramidal plane that is at a shallower angle relative to the basal plane than binding planes of moderate AFPs. These properties distinguish midge AFP from all other ice-binding proteins and the intermediate activity level fits well to the modest challenge of protecting newly emerged adult insects from late spring frosts. DATABASE: Nucleotide sequences of new midge AFP isoforms are available in the GenBank database under accession numbers KU094814-8. Sequences will be released after publication. PMID- 26896765 TI - Involvement of aquaporin-3 in epidermal growth factor receptor signaling via hydrogen peroxide transport in cancer cells. AB - Aquaporin 3 (AQP3), a water/glycerol channel protein, is capable of transporting hydrogen peroxide (H2O2). Here, we show that AQP3-mediated intracellular H2O2 is involved in epidermal growth factor (EGF)-induced cell signaling and its dependent cell function in the EGF receptor (EGFR)-positive cancer cell lines A431 and H1666. AQP3 knockdown suppressed the transport into the cells of extracellular H2O2 produced in response to EGF in A431 and H1666 cells. EGF induced Erk and Akt activation, which occurred through SHP2 and/or PTEN modulation, was impaired by AQP3 knockdown. Cell growth and migration induced by EGF stimulation were attenuated in AQP3 knockdown cells compared with those in control cells. Coincidentally, tumor growth of A431 cell xenografts in immunodeficient mice was decreased by AQP3 knockdown. Accordingly, a xenograft with AQP3 knockdown A431 cells significantly enhanced the survival of recipient mice compared with the transplantation with control cells. In addition, AQP3 associated with EGFR and NADPH oxidase 2, which we propose is linked to AQP3 producing a localized increase in intracellular H2O2 to function as a second messenger during EGFR cell signaling. Therefore, our findings suggest that AQP3 is required for EGF-EGFR cell signaling in cancer cells and is a therapeutic target for cancer progression. PMID- 26896766 TI - C2C12 myotubes inhibit the proliferation and differentiation of 3T3-L1 preadipocytes by reducing the expression of glucocorticoid receptor gene. AB - Obesity is a well-established risk factor to health for its relationship with insulin resistance, diabetes and metabolic syndrome. Myocyte-adipocyte crosstalk model plays a significant role in studying the interaction of muscle and adipose development. Previous related studies mainly focus on the effects of adipocytes on the myocytes activity, however, the influence of myotubes on the preadipocytes development remains unclear. The present study was carried out to settle this issue. Firstly, the co-culture experiment showed that the proliferation, cell cycle, and differentiation of 3T3-L1 preadipocytes were arrested, and the apoptosis was induced, by differentiated C2C12 myotubes. Next, the sensitivity of 3T3-L1 preadipocytes to glucocorticoids (GCs), which was well known as cell proliferation, differentiation, apoptosis factor, was decreased after co-cultured with C2C12 myotubes. What's more, our results showed that C2C12 myotubes suppressed the mRNA and protein expression of glucocorticoid receptor (GR) in 3T3 L1 preadipocytes, indicating the potential mechanism of GCs sensitivity reduction. Taken together, we conclude that C2C12 myotubes inhibited 3T3-L1 preadipocytes proliferation and differentiation by reducing the expression of GR. These data suggest that decreasing GR by administration of myokines may be a promising therapy for treating patients with obesity or diabetes. PMID- 26896767 TI - Qualitative and quantitative estimation of comprehensive synaptic connectivity in short- and long-term cultured rat hippocampal neurons with new analytical methods inspired by Scatchard and Hill plots. AB - To investigate comprehensive synaptic connectivity, we examined Ca(2+) responses with quantitative electric current stimulation by indium-tin-oxide (ITO) glass electrode with transparent and high electro-conductivity. The number of neurons with Ca(2+) responses was low during the application of stepwise increase of electric current in short-term cultured neurons (less than 17 days in-vitro (DIV)). The neurons cultured over 17 DIV showed two-type responses: S-shaped (sigmoid) and monotonous saturated responses, and Scatchard plots well illustrated the difference of these two responses. Furthermore, sigmoid like neural network responses over 17 DIV were altered to the monotonous saturated ones by the application of the mixture of AP5 and CNQX, specific blockers of NMDA and AMPA receptors, respectively. This alternation was also characterized by the change of Hill coefficients. These findings indicate that the neural network with sigmoid-like responses has strong synergetic or cooperative synaptic connectivity via excitatory glutamate synapses. PMID- 26896768 TI - Aldehyde dehydrogenase 1A1 stabilizes transcription factor Gli2 and enhances the activity of Hedgehog signaling in hepatocellular cancer. AB - The Gli transcription factors are primary transcriptional regulators that mediate the activation of Hedgehog (Hh) signaling. Recent studies have revealed that Gli proteins are also regulated transcriptionally and post-translationally through noncanonical mechanisms, independent of Hh signaling. However, the precise mechanisms involved in the regulation of Gli proteins remain unclear. Using a differential mass-spectrometry approach, we found that aldehyde dehydrogenase 1A1 (ALDH1A1) is associated with transcription factor Gli2. Overexpression of ALDH1A1 increased Gli2 protein levels; in contrast, ALDH1A1 depletion facilitated Gli2 degradation. In addition, Gli2 mRNA expression was not affected by ectopic expression of ALDH1A1, indicating the role of ALDH1A1 in the stabilization of Gli2. Further investigation showed that ALDH1A1 prolonged the stability of Gli2 protein in a catalytic-independent manner. Finally, we showed that overexpression of ALDH1A1 activated the Hh signaling pathway and promoted cell growth, migration and invasion in hepatocellular cancer cells. Together, these results illustrate regulatory roles of ALDH1A1 in the activation of the Hh signaling pathway and highlight a novel mechanism for the aberrant activation of the Hh signaling pathway in hepatocellular cancer cells. PMID- 26896769 TI - NME2 associates with PTPsigma to transduce signals from chondroitin sulfate proteoglycans. AB - Chondroitin sulfate proteoglycans (CSPGs) are a major component of glial scars, inhibiting axonal growth in the central nervous system. Protein tyrosine phosphatase, receptor type S (PTPsigma) has been identified as a receptor for CSPGs, whereas its downstream signaling pathway remains to be fully understood. Here, we report that nucleoside diphosphate kinase 2 (NME2) interacts with PTPsigma. We screened proteins associated with PTPsigma by mass spectrometry, and obtained NME2. Immunoprecipitation analysis revealed that NME2 associated with the PTPsigma intracellular domain in HEK-293T cells. NME2 was expressed in the cytoplasm and nucleus of cortical neurons, and knockdown of NME2 in the cortical neurons completely rescued neurite outgrowth inhibition induced by CSPGs. These results demonstrate that NME2 associates with PTPsigma to elicit neurite outgrowth inhibition in response to CSPGs. PMID- 26896770 TI - Peroxisomes in parasitic protists. AB - Representatives of all major lineages of eukaryotes contain peroxisomes with similar morphology and mode of biogenesis, indicating a monophyletic origin of the organelles within the common ancestor of all eukaryotes. Peroxisomes originated from the endoplasmic reticulum, but despite a common origin and shared morphological features, peroxisomes from different organisms show a remarkable diversity of enzyme content and the metabolic processes present can vary dependent on nutritional or developmental conditions. A common characteristic and probable evolutionary driver for the origin of the organelle is an involvement in lipid metabolism, notably H2O2-dependent fatty-acid oxidation. Subsequent evolution of the organelle in different lineages involved multiple acquisitions of metabolic processes-often involving retargeting enzymes from other cell compartments-and losses. Information about peroxisomes in protists is still scarce, but available evidence, including new bioinformatics data reported here, indicate striking diversity amongst free-living and parasitic protists from different phylogenetic supergroups. Peroxisomes in only some protists show major involvement in H2O2-dependent metabolism, as in peroxisomes of mammalian, plant and fungal cells. Compartmentalization of glycolytic and gluconeogenic enzymes inside peroxisomes is characteristic of kinetoplastids and diplonemids, where the organelles are hence called glycosomes, whereas several other excavate parasites (Giardia, Trichomonas) have lost peroxisomes. Amongst alveolates and amoebozoans patterns of peroxisome loss are more complicated. Often, a link is apparent between the niches occupied by the parasitic protists, nutrient availability, and the absence of the organelles or their presence with a specific enzymatic content. In trypanosomatids, essentiality of peroxisomes may be considered for use in anti-parasite drug discovery. PMID- 26896771 TI - A theory of interactions between polarizable dielectric spheres. AB - Surface charging or polarization can strongly affect the nature of interactions between charged dielectric objects, particularly when sharp dielectric discontinuities are involved. By relying on a generalized image method, we derive an analytical, perturbative theory of the polarization and the interactions between charged particles in many-body systems. The validity and accuracy of the theory are established by comparing its predictions to full-blown numerical solutions. The importance of polarizability is then demonstrated for clusters of dielectric spheres, as well as a periodic crystal of charged dielectric spheres arranged into a NaCl-type lattice. The analytical framework for understanding the consequences of polarization will enable molecular simulations of large systems of polarizable particles. PMID- 26896773 TI - Electrochemical behavior of chemically synthesized selenium thin film. AB - The facile and low cost simple chemical bath deposition (CBD) method is employed to synthesize red colored selenium thin films. These selenium films are characterized for structural, morphological, topographical and wettability studies. The X-ray diffraction (XRD) pattern showed the crystalline nature of selenium thin film with hexagonal crystal structure. The scanning electron microscopy (SEM) study displays selenium nanoparticles ranging from 20 to 475 nm. A specific surface area of 30.5 m(2) g(-1) is observed for selenium nanoparticles. The selenium nanoparticles hold mesopores in the range of 1.39 nm, taking benefits of the good physicochemical stability and excellent porosity. Subsequently, the electrochemical properties of selenium thin films are deliberated by cyclic voltammetry (CV), galvanostatic charge-discharge and electrochemical impedance spectroscopy (EIS) techniques. The selenium thin film shows specific capacitance (Cs) of 21.98 F g(-1) with 91% electrochemical stability. PMID- 26896772 TI - Porous titania/carbon hybrid microspheres templated by in situ formed polystyrene colloids. AB - A new strategy to synthesize hierarchical, porous titania/carbon (TiO2/C) hybrid microspheres via solvothermal reaction in N,N'-dimethyl formamide (DMF) has been developed. In situ formed polystyrene (PS) colloids have been used as templating agent and carbon source, through which TiO2/PS microspheres with a diameter of ca. 1 MUm are built by packed TiO2 nanoparticles of tens of nanometers. The TiO2/PS microspheres are converted to TiO2/C microspheres with different amounts of carbon under controlled calcination condition. The mechanism investigation unveils that the introduction of concentrated HCl creates surface tension between PS and DMF, leading to the formation of PS colloids in solution. The solvothermal treatment further promotes the formation of PS colloids and integration of the titania nanoparticles within the PS colloids. The morphology, crystallinity, nature and content of carbon, UV-Vis absorption, carbon doping, pore size distribution, pore volume, and BET surface area of the TiO2 microspheres with different amounts of carbon have been measured. The applications of the TiO2/C hybrid microspheres as photo catalyst for water splitting and lithium-ion battery anode have been demonstrated. Superior photo catalytic activity for hydrogen conversion under both full spectrum and visible light illumination compared to commercial P25 has been observed for the TiO2/C microspheres with 2 wt% of carbon. Besides, the TiO2/C microspheres with 8 wt% of carbon as lithium-ion battery anode showed a much higher capacity than the bare TiO2 microsphere anode. The origin for the enhanced performance as photo catalyst and lithium-ion battery anode is discussed. PMID- 26896774 TI - In-situ study of substrate--catalyst interactions in a Julia-Colonna epoxidation using quartz crystal microbalance with dissipation. AB - Quartz crystal microbalance with dissipation (QCM-D) analysis of the hexa-l Leucine (PLL)-catalyzed epoxidation of chalcone gives in-situ experimental evidences which demonstrate that the reaction proceeds mainly via the formation of a PLL-bound hydroperoxide complex followed by the reversible addition of chalcone. The observations offer an alternative rationalization for the viability of the preferred catalytic pathway. PMID- 26896776 TI - IL-13 Signals Independent of IL-4 Receptor-Alpha Chain to Drive Ovalbumin-Induced Dermatitis. PMID- 26896775 TI - Polypropylene Sulfide Nanoparticle p24 Vaccine Promotes Dendritic Cell-Mediated Specific Immune Responses against HIV-1. AB - Delivery of vaccine formulations into the dermis using antigen-coated microneedle patches is a promising and safe approach because of efficient antigen delivery and safety. We evaluated an intradermal vaccine using HIV-1 p24 Gag peptide conjugated polypropylene sulfide nanoparticles to induce immunity against HIV-1. This peptide-conjugated polypropylene sulfide nanoparticle formulation did not accelerate the maturation of blood- or skin-derived subsets of dendritic cells, either generated in vitro or purified ex vivo, despite efficient uptake in the absence of adjuvant. Moreover, dendritic cell-mediated capture of particulate antigen in this form induced potent HIV-1-specific CD4(+) T-cell responses, as well as B-cell-mediated antibody production. Nanoparticle-based intradermal antigen delivery may therefore provide a new option in the global effort to develop an effective vaccine against HIV-1. PMID- 26896777 TI - Stimulation of cannabinoid CB1 receptors prevents nerve-mediated airway hyperreactivity in NGF-induced inflammation in mouse airways. AB - Cannabinoids are known to inhibit neuronal activity and have significant immunomodulatory effects which suggest a role in inflammatory airway diseases. In the present study, we tested the hypothesis that cannabinoids have both acute and chronic modulatory effects on nerve-mediated contractions in NGF-induced airway inflammation. Contractions induced by electrical field stimulation (EFS) were examined in tracheal segments isolated from male BALB/c mice. Tissues were both used fresh or after four days of culture with NGF to induce airway inflammation, and further exposed to cannabinoid receptor agonists. In order to evaluate nerve density, tracheal segments were also examined by immunohistochemistry after in vitro treatments. The CB1 receptor agonists ACEA and ACPA inhibited the constant train EFS-induced contractions in both fresh and NGF-exposed tracheas, an effect that could be blocked by the CB1 receptor antagonist AM251. Culturing the tissues with NGF up-regulated the frequency-dependent EFS-contractions in isolated tracheas. This up-regulation could be inhibited by concomitant treatment with ACEA or ACPA. The treatment with NGF and/or ACEA did not affect the potency or the maximum response to carbachol. In histological sections, it was recognized that the enhanced effect induced by NGF was associated with an increase in nerve density, which, similarly, could be prevented by ACEA treatment. This study shows that stimulation of cannabinoid CB1 receptors modifies the increase of neuronal activity and density in NGF-induced airway inflammation and directly inhibits cholinergic contractions in the airways by a presynaptic mechanism. These findings indicate a protective role of CB1 receptors in airway inflammation. PMID- 26896778 TI - Pyrrolidin-2-one derivatives may reduce body weight in rats with diet-induced obesity. AB - Obesity affects an increasing number of individuals in the human population and significant importance is attached to research leading to the discovery of drug which would effectively reduce weight. The search for new drugs with anorectic activity and acting within the adrenergic system has attracted the interest of researchers. This study concerns the experimental effects on body weight of alpha2-adrenoceptor antagonists from the group of pyrrolidin-2-one derivatives in rats with diet-induced obesity. METHODS: The intrinsic activity of the test compounds at the alpha-adrenoreceptors was tested. Obesity in rats was obtained by the use of fatty diet and then the influence of the test compounds on body weight, food and water intakes, lipid and glucose profiles and glycerol and cortisol levels were determinated. The effects of the compounds on locomotor activity, body temperature, blood pressure and heart rate were tested. RESULTS: One of the test compounds (1-(3-(4-phenylpiperazin-1-yl)propyl)pyrrolidin-2-one) reduces the animal's body weight and the amount of peritoneal adipose tissue during chronic administration, at the same time it does not cause significant adverse effects on the cardiovascular system. This compound decreases temperature and elevates glycerol levels and does not change the locomotor activity and cortisol level at anti-obese dose. CONCLUSIONS: Some derivatives of pyrrolidin-2 one that act as antagonists of the alpha2-adrenoreceptor may reduce body weight. Reducing body weight for 1-(3-(4-phenylpiperazin-1-yl)propyl)pyrrolidin-2-one can be associated with decrease in food intake, body fat reduction, reduction of blood glucose, and increased thermogenesis and lipolysis. This effect cannot be the result of changes in spontaneous activity or stress. PMID- 26896779 TI - Effect of dexmedetomidine and cold stress in a rat model of neuropathic pain: Role of interleukin-6 and tumor necrosis factor-alpha. AB - Dexmedetomidine (Dex) is a novel Alpha 2-adrenoceptor agonist. It decreases sympathetic tone and attenuates the stress responses to anesthesia and surgery. People exposed to cold suffer unpleasant thermal pain, which is experienced as stress and causes the release of noradrenaline from the sympathetic terminals. The present study investigated the effects of cold stress and dexmedetomidine on chronic constriction injury (CCI) model of the sciatic nerve in rats. Sixty four male Wistar rats were divided into seven groups of eight rats each: repeated cold stress (RCS) group, sham RCS group, CCI group, sham CCI group, Dex-treated group received a single dose of Dex (5 MUg/kg), CCI+Dex group, CCI+RCS group. Interleukin-6 (IL-6) and tumor necrosis factor- alpha (TNF-alpha) levels in the serum were measured by enzyme-linked immunosorbent assay. The mean body weight of CCI, RCS, CCI+RCS, CCI+Dex and RCS+Dex groups decreased significantly compared with pre-values. Dexmedetomidine and CCI caused significant changes of the systolic, diastolic and mean blood pressure. Both RCS and CCI groups showed significant decreased of reaction time in the hot plate test. The RCS and CCI groups demonstrated a significant mechanical hyperalgesia, while pain threshold was increased in the RCS+Dex group. A significant decrease of serum IL-6 and TNF alpha was demonstrated in CCI+RCS and CCI+Dex groups. The therapeutic effectiveness of dexmedetomidine in neuropathic pain may be through inhibition of proinflammatory cytokines, primarily IL-6 and TNF-alpha. Moreover, cold stress may result in increased resistance to neuropathic pain. PMID- 26896780 TI - FMS-like tyrosine kinase 3 (FLT3) inhibitors: Molecular docking and experimental studies. AB - Activating mutations in FMS-like tyrosine kinase 3 (FLT3) occur in 25% of acute lymphoid and 30% of acute myeloid leukaemia cases. Therefore, FLT3 is a potential therapeutic target for small molecule kinase inhibitors. In this study, protein ligand interactions between FLT3 and kinase inhibitors (CEP701, PKC412, sunitinib, imatinib and dasatinib) were obtained through homology modelling and molecular docking. A cellular system for experimental testing of the inhibitors was also established by expressing wildtype and internal tandem duplication mutant FLT3 (FLT3-WT and FLT3-ITD) in FDC-P1 cells. Imatinib and dasatinib could not be docked into any of the FLT3 models, consistent with their lack of activity in the experimental assays. CEP701, PKC412 and sunitinib interacted with the ATP binding pocket of FLT3, forming H-bonds with Cys694 and Glu692. Based on the EC50 values in the cell proliferation assay, CEP701 was the most potent inhibitor; sunitinib and PKC412 were ranked second and third, respectively. Sunitinib was the most selective inhibitor, followed by PKC421 and CEP701. The potency of sunitinib and to a lesser extent CEP701 in inhibition of FLT3 autophosphorylation was lower than the cell proliferation inhibition, indicating that inhibition of FLT3 downstream proteins may contribute to the cellular effects. It was shown in this study that the docking procedure was able to differentiate FLT3 inhibitors from ineffective compounds. Additionally, interaction with the phosphate binding region in the ATP-binding pocket increased potency at the cost of selectivity. These findings can be applied in designing highly effective and selective inhibitors for FLT3 and other related kinases. PMID- 26896781 TI - The relationship between different types of dissociation and psychosis-like experiences in a non-clinical sample. AB - This study investigated whether detachment-type dissociation, compartmentalisation-type dissociation or absorption was most strongly associated with psychosis-like experiences in the general population. Healthy participants (N=215) were tested with the Dissociative Experiences Scale (DES, for detachment related dissociative experiences); the Harvard Group Scale of Hypnotic Susceptibility (HGSHS: A, for dissociative compartmentalisation); the Tellegen Absorption Scale (TAS, for non-clinical 'functional' dissociative experience); and two measures of psychotic-like experiences, the 21-item Peters et al. Delusions Inventory (PDI-21) and the Cardiff Anomalous Perceptions Scale (CAPS). In multiple regression analyses, DES and TAS but not HGSHS: A scores were found to be significantly associated with PDI-21 and CAPS overall scores. A post hoc hierarchical cluster analysis checking for cluster overlap between DES and CAPS items, and the TAS and CAPS items showed no overlap between items on the DES and CAPS and minimal overlap between TAS and CAPS items, suggesting the scales measure statistically distinct phenomena. These results show that detachment-type dissociation and absorption, but not compartmentalisation-type dissociation are significantly associated with psychosis-like experiences in a non-clinical population. PMID- 26896783 TI - Consensus recommendations for the diagnosis and treatment of multiple sclerosis in Kuwait. AB - OBJECTIVES: We aim to develop consensus recommendations to guide neurologists in the community for the diagnosis and treatment of Multiple Sclerosis (MS). METHODS: After reviewing the available literature, a group of neurologists with expertise in MS met to discuss the evidence and develop consensus recommendations for the diagnosis and treatment of MS. RESULTS: The revised 2010 McDonald criteria is the established diagnostic criteria for MS and has wide international acceptance among international MS experts. Several red flags in the history and examination, along with certain laboratory tests were pointed out to exclude MS mimickers in the diagnostic phase. The available approved disease modifying therapies (DMTs) were listed in an algorithmic fashion based on initial assessment of disease severity and subsequent disease breakthrough while on DMTs. Risk stratification based on the benefit versus risk ratio was used to help choosing the appropriate therapy to MS patients using an "individualized therapy" approach. The requirements for initiation and monitoring of treated MS patients were highlighted with emphasis on early identification of disease breakthrough, adverse events, and safety concerns. The role of multi-disciplinary MS clinics was discussed and a guide for referral to specialized MS clinics was developed. CONCLUSIONS: Consensus recommendations have been developed to guide local neurologists on the diagnosis and treatment of patients with MS. Implementation of the revised 2010 McDonald diagnostic criteria was advised while a personalized treatment approach was recommended using a treatment algorithm based on risk stratification and patient-centered outcomes. PMID- 26896782 TI - Evolution of rational vaccine designs for genital herpes immunotherapy. AB - Immunotherapeutic vaccines have emerged as a novel treatment modality for genital herpes, a sexually transmitted disease mainly caused by herpes simplex virus type 2. The approaches to identify potential vaccine antigens have evolved from classic virus attenuation and characterization of antibody and T cell responses in exposed, but seronegative individuals, to systematic screens for novel T cell antigens. Combined with implementation of novel vaccine concepts revolving around immune evasion and local recruitment of immune effectors, the development of a safe and effective therapeutic vaccine is within reach. Here, we describe the vaccine approaches that currently show promise at clinical and pre-clinical stages and link them to the evolving scientific strategies that led to their identification. PMID- 26896784 TI - The neglected need for psychological intervention in patients suffering from incidentally discovered intracranial aneurysms. AB - OBJECTIVES: Previous studies demonstrated a conspicuously elevated rate of psychiatric disorders in patients with incidental intracranial aneurysms. This study was designed to analyze the impact of this observation on the post interventional rates of PTSD, depressions and anxiety disorders in this collective. METHODS: Physically unaffected iA patients with an unremarkable medical history were included in this two center study. Pre-interventional psychiatric histories, rates of post-interventional depressions, subjective trauma, PTSD, and pre-interventional fears were determined by questionnaires (Beck Depression Inventory (BDI), Impact of Event Scale (IES), civilian Post traumatic-Stress-Disorder (PTSD) Check List (PCL-C)). Benign meningioma (M) patients served as controls. RESULTS: 58 M and 45 iA patients were enrolled. Significantly higher rates of PTSD, elevated trauma scores, and moderate/severe depressions (PTSD: p=0.0017; IES: p=0.0038; BDI: p=0.0301) were demonstrated in the iA collective. After excluding patients with a positive pre-interventional psychiatric history those differences were not reproducible. 70% of the iA patients reported an improvement of their unspecific pre-interventional symptoms, while 30% would have rated a psychological consultation as helpful. CONCLUSION: The data identifies the early psychological consultation as a relevant and by affected patients accepted treatment modification when trying to improve the outcome after treatment of incidental aneurysms. PMID- 26896785 TI - Headaches in multiple sclerosis: Cross-sectional study of a multiethnic population. AB - OBJECTIVES: Headaches in MS are common, but there is little data on the influence of race, comorbidities, MS disability and socioeconomic issues on headaches, especially migraine. We aimed at looking at prevalence and type of headache across a multiethnic MS population, and relationship between MS related clinical factors and migraine. PATIENTS AND METHODS: This is a cross-sectional study of 233 MS patients at two clinical sites, one at a county hospital, and the other a private academic center clinic. We collected demographic data, MS characteristics, and headache histories using validated survey instruments including Headache Impact Test (HIT-6) and Patient Health Questionnaire-9 (PHQ 9). The relationship between MS and migraine was examined using logistic regression. RESULTS: Majority of our patients were female (N=156, 67%), average age 44 years, with relapsing remitting MS (N=214, 92%). Our cohort was multi ethnic predominantly Whites (N=106, 46%) and Hispanics (N=87, 37%). Public sector patients were significantly disadvantaged in socioeconomic measures (p<0.0001) and younger (40 vs 47 yrs, p<0.0001), compared to the private sector patients who had a higher MS burden. Headaches were common, regardless of sector (N=115, 49.4%), the most common type being migraine (N=83, 36%). Chronic migraine was more common among Hispanics (82%) than Whites (18.2%) (p=0.012). Headache impact on daily life, measured by HIT-6 score (p=0.006) and PHQ-9 score (p=0.004) were significantly higher in the public sector. After controlling for income and education, female gender (OR 2.59, 95% CIs 1.312-5.127) and ambulatory disability were found to be more likely to suffer from migraines. CONCLUSION: Headache, especially migraine is common among MS patients regardless of socio-economic status and treatment setting. Female MS patients with walking disability and longer disease duration tend to get migraines. Hispanic MS patients have a higher likelihood of suffering from chronic migraines. Thorough headache evaluation and headache treatment are essential to comprehensive MS care. PMID- 26896786 TI - The conversion of 16beta hydroxyldehydroepiandrosterone in human serum. AB - The circulating levels of 16beta hydroxydehydroepiandrosterone (16beta OH-DHEA) are at the limit of detection (less than 10 pg/mL), unlike the serum concentrations of 16alpha-hydroxydehydroepiandrosterone (16alpha OH-DHEA, 10-300 pg/mL) in premenopausal, postmenopausal and male serum. A major reason could be the rapid conversion of 16beta OH-DHEA to 5-androstene-3beta, 17beta-diol 16 one (3beta, 17beta-diol 16-oxo) in serum due to the stereospecific structure of 16beta OH-DHEA. In ultrapure H2O, there is no apparent conversion observed while 16beta OH-DHEA (10 ng/mL) spiked in stripped or unstripped serum is quickly converted to 3beta, 17beta-diol 16-oxo at room temperature. During this conversion, a further converted product was observed with a difference in molecular weight of 16 Da from that of 16beta OH-DHEA and 3beta, 17beta-diol 16 oxo, which could be their hydroxylation product, i.e. triol-ketone. Under basic conditions, further conversion occurs. The present data can explain the practically undetectable concentration of serum 16beta OH-DHEA while 3beta, 17beta-diol 16-oxo is at the level of less than 50 pg/mL. Serum concentrations of (0.0-9.9 pg/mL for 16beta OH-DHEA, 8.9-50.7 pg/mL for 3beta, 17beta-diol 16-oxo and 10.0-285.0 pg/mL for 16alpha OH-DHEA are measured in sera of premenopausal, postmenopausal women and men over 50 years of age. PMID- 26896787 TI - Challenges in the pharmacological management of epilepsy and its causes in the elderly. AB - Epilepsy represents the third most common neurological disorders in the elderly after cerebrovascular disorders and dementias. The incidence of new-onset epilepsy peaks in this age group. The most peculiar aetiologies of late-onset epilepsy are stroke, dementia, and brain tumours. However, aetiology remains unknown in about half of the patients. Diagnosis of epilepsy may be challenging due to the frequent absence of ocular witnesses and the high prevalence of seizure-mimics (i.e. transient ischemic attacks, syncope, transient global amnesia or vertigo) in the elderly. The diagnostic difficulties are even greater when patients have cognitive impairment or cardiac diseases. The management of late-onset epilepsy deserves special considerations. The elderly can reach seizure control with low antiepileptic drugs (AEDs) doses, and seizure-freedom is possible in the vast majority of patients. Pharmacological management should take into account pharmacokinetics and pharmacodynamics of AEDs and the frequent occurrence of comorbidities and polytherapy in this age group. Evidences from double-blind and open-label studies indicate lamotrigine, levetiracetam and controlled-release carbamazepine as first line treatment in late-onset epilepsy. PMID- 26896788 TI - Clinically significant pharmacokinetic drug interactions of antiepileptic drugs with new antidepressants and new antipsychotics. AB - Antiepileptic drugs (AEDs) are frequently co-prescribed with new antidepressants (ADs) or new antipsychotics (APs). A PubMed search with no time limit was used to update the review of the clinically significant pharmacokinetic (PK) drug interactions DIs (DIs) between AEDs with new ADs and APs. Our best interpretation of what to expect regarding dosing changes in the average patient after combining AEDs with new ADs or new APs is summarized on updated tables that integrate the information on in vitro metabolism studies, therapeutic drug monitoring (TDM) studies, case report/series and prospective studies. There will be a need to periodically update these dose correction factors as new knowledge becomes available. These tables will provide some orientation to clinicians with no TDM access and may also encourage clinicians to further study TDM. The clinical relevance of the inductive properties of carbamazepine, phenytoin, phenobarbital and primidone on new ADs and new APs and the inhibitory properties of valproic acid and some new ADs, are relatively well understood. On the other hand, PK DI studies combining new AEDs with weak inductive properties (particularly oxcarbazepine doses>=1200mg/day), topiramate doses>=400mg/day, clobazam, eslicarbazepine, and rufinamide), with new ADs and new APs are needed. Valproic acid may be 1) an inhibitor and/or inducer of clozapine and olanzapine with potential for clinically relevant DIs, 2) an inhibitor of paliperidone, and 3) a weak inducer of aripiprazole. Fluoxetine and fluvoxamine are relevant inhibitors of phenytoin and valproic acid and possibly of clobazam, lacosamide, phenobarbital, or primidone. PMID- 26896789 TI - The ancient small mobilizable plasmid pALWED1.8 harboring a new variant of the non-cassette streptomycin/spectinomycin resistance gene aadA27. AB - The small mobilizable plasmid pALWED1.8 containing a novel variant of the streptomycin/spectinomycin resistance gene aadA27 was isolated from the permafrost strains of Acinetobacter lwoffii. The 4135bp plasmid carries mobA and mobC genes that mediate its mobilization by conjugative plasmids. The nucleotide sequences of mobA and mobC are similar to those of mobilization genes of the modern plasmid pRAY* and its variants, which contain aadB gene, and are widespread among the pathogenic strains of Acinetobacter baumannii. Almost identical pALWED1.8 variants were detected in modern environmental Acinetobacter strains. A highly similar plasmid was revealed in a strain of Acinetobacter parvus isolated from mouse intestine. Furthermore, we discovered six previously unidentified variants of plasmids related to pALWED1.8 and pRAY* in public databases. In contrast to most known variants of aadA which are cassette genes associated with integrons, the aadA27 variant harbored by pALWED1.8 is a non cassette, autonomously transcribed gene. Non-cassette aadA genes with 96% sequence identity to aadA27 were detected in the chromosomes of Acinetobacter gyllenbergii and several uncharacterized strains of Acinetobacter sp. Moreover, we revealed that the autonomous aadA-like genes are present in the chromosomes of many gram-positive and gram-negative bacteria. The phylogenetic analysis of amino acid sequences of all identified AadA proteins showed the following: (i) cassette aadA genes form a separate monophyletic group and mainly reside on plasmids and (ii) chromosomal non-cassette aadA genes are extremely diverse and can be inherited both vertical and via horizontal gene transfer. PMID- 26896790 TI - Prism adaptation contrasts perceptual habituation for repetitive somatosensory stimuli. AB - Prism adaptation (PA) is a non-invasive procedure that requires performing a visuo-motor pointing task while wearing prism goggles inducing a visual displacement of the pointed target. This procedure involves a reorganization of sensorimotor coordination, and induces long-lasting effects on numerous higher order cognitive functions in healthy volunteers and neglect patients. Prismatic displacement (PD) of the visual field can be induced when prisms are worn but no sensorimotor task is required. In this case, it is unlikely that any subsequent reorganization takes place. The effects of PD are short-lived in the sense that they last as long as prisms are worn. In this study we aimed, to the best of our knowledge for the first time, at investigating whether PA and PD induce changes in the perception of intensity of nociceptive and non- nociceptive somatosensory stimuli. We induced, in healthy volunteers, PD (experiment 1), or PA (experiment 2) and asked participants to rate the intensity of the stimuli applied to the hand undergoing the visuo-proprioceptive conflict (experiment 1) or adaptation (experiment 2). Our results indicate that: 1) the visuo-proprioceptive conflict induced by PD does not reduce the perceived intensity of the stimuli, 2) PA prevents perceptual habituation for both nociceptive and non-nociceptive somatosensory stimuli. Moreover, to investigate the possible underlying mechanisms of the effects of PA we conducted a third experiment in which stimuli were applied both at the adapted and the non-adapted hand. In line with the results of experiment 2, we found that perceptual habituation was prevented for stimuli applied onto the adapted hand. Moreover, we observed the same finding for stimuli applied onto the non-adapted hand. This result suggests that the detention of habituation is not merely driven by changes in spatial attention allocation. Taken together, these data indicate that prisms can affect the perceived intensity of somatosensory stimuli, but only when PA is induced. PMID- 26896791 TI - Effects of imputation on correlation: implications for analysis of mass spectrometry data from multiple biological matrices. AB - With expanded access to, and decreased costs of, mass spectrometry, investigators are collecting and analyzing multiple biological matrices from the same subject such as serum, plasma, tissue and urine to enhance biomarker discoveries, understanding of disease processes and identification of therapeutic targets. Commonly, each biological matrix is analyzed separately, but multivariate methods such as MANOVAs that combine information from multiple biological matrices are potentially more powerful. However, mass spectrometric data typically contain large amounts of missing values, and imputation is often used to create complete data sets for analysis. The effects of imputation on multiple biological matrix analyses have not been studied. We investigated the effects of seven imputation methods (half minimum substitution, mean substitution, k-nearest neighbors, local least squares regression, Bayesian principal components analysis, singular value decomposition and random forest), on the within-subject correlation of compounds between biological matrices and its consequences on MANOVA results. Through analysis of three real omics data sets and simulation studies, we found the amount of missing data and imputation method to substantially change the between matrix correlation structure. The magnitude of the correlations was generally reduced in imputed data sets, and this effect increased with the amount of missing data. Significant results from MANOVA testing also were substantially affected. In particular, the number of false positives increased with the level of missing data for all imputation methods. No one imputation method was universally the best, but the simple substitution methods (Half Minimum and Mean) consistently performed poorly. PMID- 26896792 TI - Hetero-enzyme-based two-round signal amplification strategy for trace detection of aflatoxin B1 using an electrochemical aptasensor. AB - An electrochemical aptasensor for trace detection of aflatoxin B1 (AFB1) was developed by using an aptamer as the recognition unit while adopting the telomerase and EXO III based two-round signal amplification strategy as the signal enhancement units. The telomerase amplification was used to elongate the ssDNA probes on the surface of gold nanoparticles, by which the signal response range of the signal-off model electrochemical aptasensor could be correspondingly enlarged. Then, the EXO III amplification was used to hydrolyze the 3'-end of the dsDNA after the recognition of target AFB1, which caused the release of bounded AFB1 into the sensing system, where it participated in the next recognition sensing cycle. With this two-round signal amplified electrochemical aptasensor, target AFB1 was successfully measured at trace concentrations with excellent detection limit of 0.6*10(-4)ppt and satisfied specificity due to the excellent affinity of the aptamer against AFB1. Based on this designed two-round signal amplification strategy, both the sensing range and detection limit were greatly improved. This proposed ultrasensitive electrochemical aptasensor method was also validated by comparison with the classic instrumental methods. Importantly, this hetero-enzyme based two-round signal amplified electrochemical aptasensor offers a great promising protocol for ultrasensitive detection of AFB1 and other mycotoxins by replacing the core recognition sequence of the aptamer. PMID- 26896793 TI - Fabrication of an electrochemical DNA-based biosensor for Bacillus cereus detection in milk and infant formula. AB - This paper describes fabrication of a DNA-based Au-nanoparticle modified pencil graphite electrode (PGE) biosensor for detection of Bacillus cereus, causative agent of two types of food-borne disease, i.e., emetic and diarrheal syndrome. The sensing element of the biosensor was comprised of gold nanoparticles (GNPs) self-assembled with single-stranded DNA (ssDNA) of nheA gene immobilized with thiol linker on the GNPs modified PGE. The size, shape and dispersion of the GNPs were characterized by field emission scanning electron microscope (FESEM). Detection of B. cereus was carried out based on an increase in the charge transfer resistance (Rct) of the biosensor due to hybridization of the ss-DNA with target DNA. An Atomic force microscope (AFM) was used to confirm the hybridization. The biosensor sensitivity in pure cultures of B. cereus was found to be 10(0) colony forming units per milliliter (CFU/mL) with a detection limit of 9.4 * 10(-12) mol L(-1). The biosensor could distinguish complementary from mismatch DNA sequence. The proposed biosensor exhibited a rapid detection, low cost, high sensitivity to bacterial contamination and could exclusively and specifically detect the target DNA sequence of B. cereus from other bacteria that can be found in dairy products. Moreover, the DNA biosensor exhibited high reproducibility and stability, thus it may be used as a suitable biosensor to detect B. cereus and to become a portable system for food quality control. PMID- 26896794 TI - Long period fiber grating nano-optrode for cancer biomarker detection. AB - We report an innovative fiber optic nano-optrode based on Long Period Gratings (LPGs) working in reflection mode for the detection of human Thyroglobulin (TG), a protein marker of differentiated thyroid cancer. The reflection-type LPG (RT LPG) biosensor, coated with a single layer of atactic polystyrene (aPS) onto which a specific, high affinity anti-Tg antibody was adsorbed, allowed the label free detection of Tg in the needle washouts of fine-needle aspiration biopsies, at concentrations useful for pre- and post-operative assessment of the biomarker levels. Analyte recognition and capture were confirmed with a parallel on fiber ELISA-like assay using, in pilot tests, the biotinylated protein and HRP-labeled streptavidin for its detection. Dose-dependent experiments showed that the detection is linearly dependent on concentration within the range between 0 and 4 ng/mL, while antibody saturation occurs for higher protein levels. The system is characterized by a very high sensitivity and specificity allowing the ex-vivo detection of sub ng/ml concentrations of human Tg from needle washouts of fine needle aspiration biopsies of thyroid nodule from different patients. PMID- 26896795 TI - Activation of Short and Long Chain Fatty Acid Sensing Machinery in the Ileum Lowers Glucose Production in Vivo. AB - Evidence continues to emerge detailing the myriad of ways the gut microbiota influences host energy homeostasis. Among the potential mechanisms, short chain fatty acids (SCFAs), the byproducts of microbial fermentation of dietary fibers, exhibit correlative beneficial metabolic effects in humans and rodents, including improvements in glucose homeostasis. The underlying mechanisms, however, remain elusive. We here report that one of the main bacterially produced SCFAs, propionate, activates ileal mucosal free fatty acid receptor 2 to trigger a negative feedback pathway to lower hepatic glucose production in healthy rats in vivo We further demonstrate that an ileal glucagon-like peptide-1 receptor dependent neuronal network is necessary for ileal propionate and long chain fatty acid sensing to regulate glucose homeostasis. These findings highlight the potential to manipulate fatty acid sensing machinery in the ileum to regulate glucose homeostasis. PMID- 26896796 TI - Proteomic Analysis Reveals Branch-specific Regulation of the Unfolded Protein Response by Nonsense-mediated mRNA Decay. AB - Nonsense-mediated mRNA decay (NMD) has originally been described as a surveillance mechanism to inhibit the expression of mRNAs with truncated open reading frames (ORFs) and to contribute to the fidelity of gene expression. It is now recognized that NMD also controls the expression of physiological genes with "intact" mRNA. Stress can decrease NMD efficiency and thus increase the mRNA levels of physiological NMD targets. As stress can also inhibit translation, the net outcome for shaping the proteome is difficult to predict. We have thus analyzed de novo protein synthesis in response to NMD inhibition or the induction of mild endoplasmic reticulum (ER) stress by treatment of cells with the reducing agent dithiotreitol (DTT). For this purpose, we combined pulsed azidohomoalanine (AHA) and stable isotope labeling by amino acids in cell culture (SILAC). Labeled proteins were purified by click chemistry-based covalent coupling to agarose beads, trypsinized, fractionated, and analyzed by mass spectrometry (MS). We find that mild ER stress up-regulates the de novo synthesis of components of all three branches of the unfolded protein response (PERK, IRE1 and ATF6) without increasing eIF2alpha phosphorylation or impairing of protein translation. In contrast, inhibition of NMD induces de novo protein synthesis of downstream targets of the PERK and IRE1 pathways, whereas we could not detect regulation of ATF6-responsive genes. These data thus support a model that implicates a positive feedback loop of ER stress inhibiting NMD efficiency which further promotes the ER stress response in a branch-specific manner. PMID- 26896797 TI - A high definition look at the NF-Y regulome reveals genome-wide associations with selected transcription factors. AB - NF-Y is a trimeric transcription factor (TF), binding the CCAAT box element, for which several results suggest a pioneering role in activation of transcription. In this work, we integrated 380 ENCODE ChIP-Seq experiments for 154 TFs and cofactors with sequence analysis, protein-protein interactions and RNA profiling data, in order to identify genome-wide regulatory modules resulting from the co association of NF-Y with other TFs. We identified three main degrees of co association with NF-Y for sequence-specific TFs. In the most relevant one, we found TFs having a significant overlap with NF-Y in their DNA binding loci, some with a precise spacing of binding sites with respect to the CCAAT box, others (FOS, Sp1/2, RFX5, IRF3, PBX3) mostly lacking their canonical binding site and bound to arrays of well spaced CCAAT boxes. As expected, NF-Y binding also correlates with RNA Pol II General TFs and with subunits of complexes involved in the control of H3K4 methylations. Co-association patterns are confirmed by protein-protein interactions, and correspond to specific functional categorizations and expression level changes of target genes following NF-Y inactivation. These data define genome-wide rules for the organization of NF-Y centered regulatory modules, supporting a model of distinct categorization and synergy with well defined sets of TFs. PMID- 26896799 TI - SRAMP: prediction of mammalian N6-methyladenosine (m6A) sites based on sequence derived features. AB - N(6)-methyladenosine (m(6)A) is a prevalent RNA methylation modification involved in the regulation of degradation, subcellular localization, splicing and local conformation changes of RNA transcripts. High-throughput experiments have demonstrated that only a small fraction of the m(6)A consensus motifs in mammalian transcriptomes are modified. Therefore, accurate identification of RNA m(6)A sites becomes emergently important. For the above purpose, here a computational predictor of mammalian m(6)A site named SRAMP is established. To depict the sequence context around m(6)A sites, SRAMP combines three random forest classifiers that exploit the positional nucleotide sequence pattern, the K nearest neighbor information and the position-independent nucleotide pair spectrum features, respectively. SRAMP uses either genomic sequences or cDNA sequences as its input. With either kind of input sequence, SRAMP achieves competitive performance in both cross-validation tests and rigorous independent benchmarking tests. Analyses of the informative features and overrepresented rules extracted from the random forest classifiers demonstrate that nucleotide usage preferences at the distal positions, in addition to those at the proximal positions, contribute to the classification. As a public prediction server, SRAMP is freely available at http://www.cuilab.cn/sramp/. PMID- 26896798 TI - alphaCP binding to a cytosine-rich subset of polypyrimidine tracts drives a novel pathway of cassette exon splicing in the mammalian transcriptome. AB - Alternative splicing (AS) is a robust generator of mammalian transcriptome complexity. Splice site specification is controlled by interactions of cis-acting determinants on a transcript with specific RNA binding proteins. These interactions are frequently localized to the intronic U-rich polypyrimidine tracts (PPT) located 5' to the majority of splice acceptor junctions. alphaCPs (also referred to as polyC-binding proteins (PCBPs) and hnRNPEs) comprise a subset of KH-domain proteins with high affinity and specificity for C-rich polypyrimidine motifs. Here, we demonstrate that alphaCPs promote the splicing of a defined subset of cassette exons via binding to a C-rich subset of polypyrimidine tracts located 5' to the alphaCP-enhanced exonic segments. This enhancement of splice acceptor activity is linked to interactions of alphaCPs with the U2 snRNP complex and may be mediated by cooperative interactions with the canonical polypyrimidine tract binding protein, U2AF65. Analysis of alphaCP targeted exons predicts a substantial impact on fundamental cell functions. These findings lead us to conclude that the alphaCPs play a direct and global role in modulating the splicing activity and inclusion of an array of cassette exons, thus driving a novel pathway of splice site regulation within the mammalian transcriptome. PMID- 26896800 TI - Quantitative sampling of conformational heterogeneity of a DNA hairpin using molecular dynamics simulations and ultrafast fluorescence spectroscopy. AB - Molecular dynamics (MD) simulations and time resolved fluorescence (TRF) spectroscopy were combined to quantitatively describe the conformational landscape of the DNA primary binding sequence (PBS) of the HIV-1 genome, a short hairpin targeted by retroviral nucleocapsid proteins implicated in the viral reverse transcription. Three 2-aminopurine (2AP) labeled PBS constructs were studied. For each variant, the complete distribution of fluorescence lifetimes covering 5 orders of magnitude in timescale was measured and the populations of conformers experimentally observed to undergo static quenching were quantified. A binary quantification permitted the comparison of populations from experimental lifetime amplitudes to populations of aromatically stacked 2AP conformers obtained from simulation. Both populations agreed well, supporting the general assumption that quenching of 2AP fluorescence results from pi-stacking interactions with neighboring nucleobases and demonstrating the success of the proposed methodology for the combined analysis of TRF and MD data. Cluster analysis of the latter further identified predominant conformations that were consistent with the fluorescence decay times and amplitudes, providing a structure-based rationalization for the wide range of fluorescence lifetimes. Finally, the simulations provided evidence of local structural perturbations induced by 2AP. The approach presented is a general tool to investigate fine structural heterogeneity in nucleic acid and nucleoprotein assemblies. PMID- 26896801 TI - Substrate recognition and cleavage-site selection by a single-subunit protein only RNase P. AB - RNase P is the enzyme that removes 5' extensions from tRNA precursors. With its diversity of enzyme forms-either protein- or RNA-based, ranging from single polypeptides to multi-subunit ribonucleoproteins-the RNase P enzyme family represents a unique model system to compare the evolution of enzymatic mechanisms. Here we present a comprehensive study of substrate recognition and cleavage-site selection by the nuclear single-subunit proteinaceous RNase P PRORP3 from Arabidopsis thaliana. Compared to bacterial RNase P, the best characterized RNA-based enzyme form, PRORP3 requires a larger part of intact tRNA structure, but little to no determinants at the cleavage site or interactions with the 5' or 3' extensions of the tRNA. The cleavage site depends on the combined dimensions of acceptor stem and T domain, but also requires the leader to be single-stranded. Overall, the single-subunit PRORP appears mechanistically more similar to the complex nuclear ribonucleoprotein enzymes than to the simpler bacterial RNase P. Mechanistic similarity or dissimilarity among different forms of RNase P thus apparently do not necessarily reflect molecular composition or evolutionary relationship. PMID- 26896802 TI - Mechanism of DNA loading by the DNA repair helicase XPD. AB - The xeroderma pigmentosum group D (XPD) helicase is a component of the transcription factor IIH complex in eukaryotes and plays an essential role in DNA repair in the nucleotide excision repair pathway. XPD is a 5' to 3' helicase with an essential iron-sulfur cluster. Structural and biochemical studies of the monomeric archaeal XPD homologues have aided a mechanistic understanding of this important class of helicase, but several important questions remain open. In particular, the mechanism for DNA loading, which is assumed to require large protein conformational change, is not fully understood. Here, DNA binding by the archaeal XPD helicase from Thermoplasma acidophilum has been investigated using a combination of crystallography, cross-linking, modified substrates and biochemical assays. The data are consistent with an initial tight binding of ssDNA to helicase domain 2, followed by transient opening of the interface between the Arch and 4FeS domains, allowing access to a second binding site on helicase domain 1 that directs DNA through the pore. A crystal structure of XPD from Sulfolobus acidocaldiarius that lacks helicase domain 2 has an otherwise unperturbed structure, emphasizing the stability of the interface between the Arch and 4FeS domains in XPD. PMID- 26896804 TI - Studying Z-DNA and B- to Z-DNA transitions using a cytosine analogue FRET-pair. AB - Herein, we report on the use of a tricyclic cytosine FRET pair, incorporated into DNA with different base pair separations, to study Z-DNA and B-Z DNA junctions. With its position inside the DNA structure, the FRET pair responds to a B- to Z DNA transition with a distinct change in FRET efficiency for each donor/acceptor configuration allowing reliable structural probing. Moreover, we show how fluorescence spectroscopy and our cytosine analogues can be used to determine rate constants for the B- to Z-DNA transition mechanism. The modified cytosines have little influence on the transition and the FRET pair is thus an easily implemented and virtually non-perturbing fluorescence tool to study Z-DNA. This nucleobase analogue FRET pair represents a valuable addition to the limited number of fluorescence methods available to study Z-DNA and we suggest it will facilitate, for example, deciphering the B- to Z-DNA transition mechanism and investigating the interaction of DNA with Z-DNA binding proteins. PMID- 26896803 TI - Reversal of epigenetic promoter silencing in Friedreich ataxia by a class I histone deacetylase inhibitor. AB - Friedreich ataxia, the most prevalent inherited ataxia, is caused by an expanded GAA triplet-repeat sequence in intron 1 of the FXN gene. Repressive chromatin spreads from the expanded GAA triplet-repeat sequence to cause epigenetic silencing of the FXN promoter via altered nucleosomal positioning and reduced chromatin accessibility. Indeed, deficient transcriptional initiation is the predominant cause of transcriptional deficiency in Friedreich ataxia. Treatment with 109, a class I histone deacetylase (HDAC) inhibitor, resulted in increased level of FXN transcript both upstream and downstream of the expanded GAA triplet repeat sequence, without any change in transcript stability, suggesting that it acts via improvement of transcriptional initiation. Quantitative analysis of transcriptional initiation via metabolic labeling of nascent transcripts in patient-derived cells revealed a >3-fold increase (P < 0.05) in FXN promoter function. A concomitant 3-fold improvement (P < 0.001) in FXN promoter structure and chromatin accessibility was observed via Nucleosome Occupancy and Methylome Sequencing, a high-resolution in vivo footprint assay for detecting nucleosome occupancy in individual chromatin fibers. No such improvement in FXN promoter function or structure was observed upon treatment with a chemically-related inactive compound (966). Thus epigenetic promoter silencing in Friedreich ataxia is reversible, and the results implicate class I HDACs in repeat-mediated promoter silencing. PMID- 26896805 TI - Structural basis for PHDVC5HCHNSD1-C2HRNizp1 interaction: implications for Sotos syndrome. AB - Sotos syndrome is an overgrowth syndrome caused by mutations within the functional domains ofNSD1 gene coding for NSD1, a multidomain protein regulating chromatin structure and gene expression. In particular, PHDVC5HCHNSD1 tandem domain, composed by a classical (PHDV) and an atypical (C5HCH) plant homeo-domain (PHD) finger, is target of several pathological missense-mutations. PHDVC5HCHNSD1 is also crucial for NSD1-dependent transcriptional regulation and interacts with the C2HR domain of transcriptional repressor Nizp1 (C2HRNizp1)in vitro To get molecular insights into the mechanisms dictating the patho-physiological relevance of the PHD finger tandem domain, we solved its solution structure and provided a structural rationale for the effects of seven Sotos syndrome point mutations. To investigate PHDVC5HCHNSD1 role as structural platform for multiple interactions, we characterized its binding to histone H3 peptides and to C2HRNizp1 by ITC and NMR. We observed only very weak electrostatic interactions with histone H3 N-terminal tails, conversely we proved specific binding to C2HRNizp1 We solved C2HRNizp1 solution structure and generated a 3D model of the complex, corroborated by site-directed mutagenesis. We suggest a mechanistic scenario where NSD1 interactions with cofactors such as Nizp1 are impaired by PHDVC5HCHNSD1 pathological mutations, thus impacting on the repression of growth promoting genes, leading to overgrowth conditions. PMID- 26896807 TI - Trajectory and predictors of quality of life in first episode psychotic mania. AB - BACKGROUND: Little is known about the trajectory of quality of life (QoL) following a first episode of psychotic mania in bipolar disorder (BD). This 18 month longitudinal study investigated the trajectory of QoL, and the influence of premorbid adjustment and symptoms on 18-month QoL in a cohort of young people experiencing a first episode of psychotic mania. METHODS: As part of an overarching clinical trial, at baseline, sixty participants presenting with a first episode of psychotic mania (BD Type 1 - DSM-IV) completed symptomatic and functional assessments in addition to the Premorbid Adjustment Scale - General Subscale. Symptom measures were repeated at 18-month follow up. QoL was rated using the Quality of Life Scale (QLS) at designated time points. RESULTS: Mean QLS scores at initial measurement (8 weeks) were 61% of the maximum possible score, increasing significantly to 70% at 12 months, and 71.2% at 18-month follow up. Premorbid adjustment and 18-month depressive symptoms were significantly associated with QoL at 18-month follow-up. LIMITATIONS: Study limitations include the small sample size, inclusion of participants with psychotic mania only, use of measures originally designed for use with schizophrenia spectrum disorders, and lack of premorbid or baseline measurement of QoL. CONCLUSIONS: Results suggest that QoL can be maintained early in BD, and reinforce the importance of assertively treating depressive symptoms throughout the course of this disorder. The emergence of a link between premorbid adjustment and poorer QoL in this cohort highlights the importance of assessing facets of adjustment when planning psychological interventions. PMID- 26896806 TI - Structural and mutational analysis of archaeal ATP-dependent RNA ligase identifies amino acids required for RNA binding and catalysis. AB - An ATP-dependent RNA ligase from Methanobacterium thermoautotrophicum (MthRnl) catalyzes intramolecular ligation of single-stranded RNA to form a closed circular RNA via covalent ligase-AMP and RNA-adenylylate intermediate. Here, we report the X-ray crystal structures of an MthRnl*ATP complex as well as the covalent MthRnl-AMP intermediate. We also performed structure-guided mutational analysis to survey the functions of 36 residues in three component steps of the ligation pathway including ligase-adenylylation (step 1), RNA adenylylation (step 2) and phosphodiester bond synthesis (step 3). Kinetic analysis underscored the importance of motif 1a loop structure in promoting phosphodiester bond synthesis. Alanine substitutions of Thr117 or Arg118 favor the reverse step 2 reaction to deadenylate the 5'-AMP from the RNA-adenylate, thereby inhibiting step 3 reaction. Tyr159, Phe281 and Glu285, which are conserved among archaeal ATP dependent RNA ligases and are situated on the surface of the enzyme, are required for RNA binding. We propose an RNA binding interface of the MthRnl based on the mutational studies and two sulfate ions that co-crystallized at the active site cleft in the MthRnl-AMP complex. PMID- 26896808 TI - Telomere length and telomere repeating factors: Cellular markers for post traumatic stress disorder-like model. AB - OBJECTIVE: The aim of the present study was to explore the telomere length of peripheral blood leukocytes from a rat model of post-traumatic stress disorder (PTSD), as well as the expression level of telomere-binding protein in the hippocampal CA1 region. METHODS: The PTSD model was established with 42 adult male Wistar rats. The relative telomere length of the leukocytes was measured by real-time fluorescence quantitative polymerase chain reaction, and the expression levels of telomere repeating factor 1 (TRF1) and telomere repeating factor 2 (TRF2) in the hippocampal CA1 region of the PTSD rat model were determined by immunofluorescence technology. The covariance analysis of repeated measurements by the mixed model approach was used for the telomere length analysis. The comparison of averaged data among groups was performed using least significant difference and analysis of variance. The Student's t test or the Mann-Whitney U test was used for intragroup comparison. The association study among groups was conducted using the Spearman test. RESULTS: The shortening speed of telomere length significantly accelerated in rats after Single Prolonged Stress (SPS) stimulation (P<0.05). The expression levels of TRF1 and TRF2 increased with the progress of PTSD, and the expression peak was shown in day 14, which was significantly different from the control group (P<0.05). CONCLUSION: The shortening speed of the telomere length of peripheral blood leukocytes accelerated in PTSD rats, and the expression levels of TRF1 and TRF2 increased in hippocampus, both of which were closely associated with the pathological progress of the PTSD-like model and unfavorable prognosis. PMID- 26896809 TI - Adult attachment representation moderates psychotherapy treatment efficacy in clinically depressed inpatients. AB - BACKGROUND: We explored in a sample of clinically depressed patients the influence of attachment security and unresolved trauma on psychotherapeutic outcome as well as changes in attachment representation through psychotherapeutic intervention. METHODS: The sample consisted of 85 women (aged 19-52), 43 clinically depressed patients from a psychosomatic inpatient unit, and 42 healthy control subjects matched for age and education. Average length of hospitalization in the patient group was eight weeks. Attachment representations were assessed with the Adult Attachment Interview at the time of admission (baseline) and at discharge. Depressive symptoms were measured using the PHQ-9 at T1 and T2. RESULTS: Insecure attachment representations were overrepresented in depressed patients. Treatment effects were moderated by baseline attachment representation: patients with higher attachment security scores at admission benefited more from the inpatient treatment and were less depressed at time of discharge than less secure patients (eta(2)=.07). Generally, attachment security increased (eta(2)=.19) and depressive symptoms decreased (eta(2)=.23) after inpatient psychotherapy treatment in the patient group. No significant effects for unresolved symptoms were found. LIMITATIONS: The study is not a randomized controlled study, but used a quasi-experimental matched control group design with female subjects only. CONCLUSIONS: Our results suggest that attachment representations play a major role in both the development and treatment of clinical depression. Baseline attachment security may influence psychotherapeutic outcome, perhaps through relational factors such as therapeutic working alliance. Inpatient psychotherapy may also need to address psychological issues associated with depression such as attachment insecurity. PMID- 26896811 TI - What happens to the course of bipolar disorder after electroconvulsive therapy? AB - BACKGROUND: Bipolar disorder (BD) encompasses manic and depressive episodes and an illness-free interval. Treatments used in BD patients may influence the ill phases with different actions on the illness-free interval. METHODS: We performed a naturalistic mirror-image retrospective study analyzing the number of episodes and admissions in 41 BD patients for the same period of time of 5 years before and after electroconvulsive therapy (ECT). Furthermore, we assessed the duration of free intervals before and after ECT as a sign of prolonged well-being. Univariate analysis with t-test was used to compare differences before and after ECT, while analysis of variance was used to compare factors possibly associated with the efficacy on free-interval of ECT. RESULTS: Comparing the 5-year periods before and after ECT, we found significantly longer [13.2 +/- 9.0 months before ECT to 25.1 +/- 19.1 after treatment (t=3.8; p<0.0001)] free intervals, as well as significant reductions in the number of episodes [5.9 +/- 3.0 before ECT to 1.0 +/- 1.7 after treatment (t=9.3; p<0.0001)], and in the number of admissions [2.2 +/- 1.3 before ECT to 0.2 +/- 0.5 after treatment (t=9.4; p<0.0001)]. LIMITATIONS: The main limitations of this study consisted in the relatively small sample size, the mirror-image retrospective naturalistic study design and possibly patient selection bias. CONCLUSIONS: Electroconvulsive therapy seemed to increase free-intervals and reduced number of BD episodes and admissions. It is plausible that ECT, along with suspending antidepressant treatment, might carry intrinsic stabilizing effect on the course of BD. PMID- 26896812 TI - Diagnostic instability of recurrence and the impact on recurrence rates in depressive and anxiety disorders. AB - BACKGROUND: Despite increasing evidence for the diagnostic instability between and within depressive and anxiety disorders, most studies report solely on the recurrence rates of the specific index disorders. Neglecting this evidence has an inherent risk of underestimating recurrence rates of depressive and anxiety disorders. This study investigates the impact of diagnostic instability of recurrence rates in depression and anxiety. METHODS: Data were derived from the Netherlands Study of Depression and Anxiety (NESDA). The sample of 656 participants had a panic disorder with or without agoraphobia, agoraphobia, social phobia, generalized anxiety disorder, major depressive disorder or dysthymia, and a subsequent remission. Recurrence rates of index disorders (diagnostically stable recurrence) and newly arisen anxiety or depressive disorders (diagnostically unstable recurrence), were calculated over a 4-year follow-up period. RESULTS: In anxiety disorders (n=281), the recurrence rate is more than doubled, from 23.8% with a stable recurrence, to 54.8%, when diagnostically unstable recurrences are included. In depressive disorders (N=173) the recurrence rate increases from 37.6% to 49.7%, and in comorbid anxiety and depressive disorders (N=202) the diagnostically unstable recurrences increase from 54.0% to 66.3%. LIMITATIONS: Attrition during follow up may have biased the results; remission was defined as absence of symptoms for 1 month; very short term remission and recurrence patterns were not assessed. CONCLUSIONS: Diagnostically unstable recurrences have a significant impact on recurrence rates, with the greatest instability for anxiety disorders. When only diagnostically stable recurrences are assessed, recurrence rates are highly underrated and provide biased estimates of the true course of these disorders. PMID- 26896810 TI - Effect of transcutaneous auricular vagus nerve stimulation on major depressive disorder: A nonrandomized controlled pilot study. AB - BACKGROUND: Depression presents a significant burden to both patients and society. One treatment that has emerged is vagus nerve stimulation (VNS), an FDA approved physical treatment for depressive disorders. However, the application of this intervention has been limited by the involvement of surgery and potential side effects. The aim of this study is to explore the effectiveness of stimulating the superficial branches of the vagus nerve as a solo treatment for MDD. METHODS: This is a nonrandomized, controlled study. The first cohort of patients (n=91) only received transcutaneous auricular VNS (taVNS) for 12 weeks. In the second cohort (n=69), patients first received 4 weeks of sham taVNS followed by 8 weeks of taVNS. All treatments were self-administered by the patients at home after they received training from the hospitals. The primary outcome measurement was the 24-item Hamilton Depression Rating Scale measured at weeks 0, 4, 8, and 12. Data analysis included a timelag analysis comparing (1) real and sham taVNS groups at week 4; (2) the real taVNS group at week 4 vs the sham taVNS group at week 8 (fourth week of real taVNS following 4 weeks of sham); and (3) the real taVNS group at week 8 vs the sham taVNS group at week 12 (eighth week of real taVNS following sham). RESULTS: After four weeks of treatment, MDD patients in the taVNS group showed greater improvement than patients in the sham taVNS group as indicated by Hamilton score changes as well as response and remission rates at week four. In addition, we also found that the clinical improvements continued until week 12 during taVNS. LIMITATIONS: Patients were not randomized in this study. CONCLUSIONS: Our results suggest that taVNS is a promising, safe, and cost-effective therapeutic method for mild and moderate MDD. PMID- 26896813 TI - The German version of the Interpersonal Needs Questionnaire (INQ)- Dimensionality, psychometric properties and population-based norms. AB - PURPOSE: The Interpersonal Needs Questionnaire (INQ) assesses the two interpersonal constructs perceived burdensomeness (PB) and thwarted belongingness (TB) that lead to suicidal ideation, according to the interpersonal theory of suicide (IPTS). The present study investigates dimensionality and psychometric properties of the German version of the INQ in a population-based representative sample and delivers norm values. METHODS: The German INQ as well as measures of depression and past suicidality were administered to a population-based representative sample of the German general population (n=2513) to analyze its dimensionality and construct validity by confirmatory factor analysis and correlational analysis. RESULTS: Results of the confirmatory factor analysis were in line with the assumption of two-dimensionality of the INQ. The two subscales showed very good internal consistencies (alpha >= 0.89) as well as correlations with depression and suicidality that indicate convergent validity. There were no gender effects but slight age effects in the scores of both subscales. Population based norms are provided. LIMITATIONS: Convergent validity was solely examined with measures of depression and suicidal thoughts instead of further suitable constructs like loneliness and social support. Divergent validity was not investigated in the study. CONCLUSION: The German version of the INQ shows good psychometric properties making it a promising tool for assessing PB and TB. The provided norms enable researchers to compare INQ scores of their samples with reference values of a population-based representative sample. PMID- 26896814 TI - Can neuroimaging disentangle bipolar disorder? AB - BACKGROUND: Bipolar disorder heterogeneity is large, leading to difficulties in identifying neuropathophysiological and etiological mechanisms and hindering the formation of clinically homogeneous patient groups in clinical trials. Identifying markers of clinically more homogeneous groups would help disentangle BD heterogeneity. Neuroimaging may aid in identifying such groups by highlighting specific biomarkers of BD subtypes or clinical dimensions. METHODS: We performed a systematic literature search of the neuroimaging literature assessing biomarkers of relevant BD phenotypes (type-I vs. II, presence vs. absence of psychotic features, suicidal behavior and impulsivity, rapid cycling, good vs. poor medication response, age at onset, cognitive performance and circadian abnormalities). RESULTS: Consistent biomarkers were associated with suicidal behavior, i.e. frontal/anterior alterations (prefrontal and cingulate grey matter, prefrontal white matter) in patients with a history of suicide attempts; and with cognitive performance, i.e. involvement of frontal and temporal regions, superior and inferior longitudinal fasciculus, right thalamic radiation, and corpus callosum in executive dysfunctions. For the other dimensions and sub-types studied, no consistent biomarkers were identified. LIMITATIONS: Studies were heterogeneous both in methodology and outcome. CONCLUSIONS: Though theoretically promising, neuroimaging has not yet proven capable of disentangling subtypes and dimensions of bipolar disorder, due to high between-study heterogeneity. We issue recommendations for future studies. PMID- 26896815 TI - Prescribing trends for sodium valproate in Ireland. AB - PURPOSE: This study was undertaken to describe prescribing practice for the anti convulsant drug (AED) Sodium Valproate (VPA) in an Irish population of woman of childbearing age during the period of the emergence of new data showing a high rate of developmental abnormalities in offspring of women who took VPA during pregnancy. METHODS: All prescriptions dispensed from community pharmacies in Ireland between 2008 and 2013 inclusive were examined for women aged 16-44 years from all three drug reimbursement schemes in Ireland. Numbers of prescriptions and women on AEDs were identified, as was the rural/urban distribution of the drug along with co-prescribing of folic acid and the oral contraceptive pill. All data analysis was conducted using SAS v9.3. RESULTS: The rate of prescribing of VPA in Ireland declined slightly from 3.5/1000 per eligible population in 2008 to 3.14/1000 in 2013. While rates of prescribing fell for epilepsy, there appeared to be a rise in prescription for other indications of VPA. In 2013, co prescription of folic acid or oral contraceptives was relatively low across all community schemes. Finally, an address distant from academic specialist centers predicted a higher exposure to VPA. CONCLUSION: Recently the European Medicine's Agency suggested that alternatives to VPA be considered before prescribing to women of childbearing age. Despite this, the rate of VPA prescribing in Ireland appears to be increasing for indications other than epilepsy. It may be necessary to improve the dissemination of information about the potential negative effects of VPA in this population. PMID- 26896816 TI - Statins: An undesirable class of aquatic contaminants? AB - Emerging pollutants, such as pharmaceuticals, may pose a considerable environment risk. Hypocholesterolaemic drugs such as statins are among the most prescribed human pharmaceuticals in western European countries. In vertebrates, this therapeutic class disrupts the cholesterol synthesis by inhibiting the enzyme 3 hydroxy-3-methyl-glutaryl-CoA reductase (HMGR), responsible for the limiting step in the mevalonate pathway. Recently, functional studies have shown that statins competitively inhibit HMGR in vertebrates and arthropods, two taxa that have diverged over 450 million years ago. Importantly, chronic simvastatin exposure disrupts crustacean reproduction and development at environmentally relevant concentrations. Hence, a fundamental question emerges: what is the taxonomic scope of statins-induced HMGR inhibition across metazoans? Here, we address this central question in a large sampling of metazoans using comparative genomics, homology modelling and molecular docking. Sequence alignment of metazoan HMGRs allowed the annotation of highly conserved catalytic, co-factor and substrate binding sites, including residues highjacked for statin binding. Furthermore, molecular docking shows that the catalytic domains of metazoan HMGRs are highly conserved regarding interactions, not only with HMG-CoA, but also with both simvastatin and atorvastatin, the top prescribed statins in Europe and USA. Hence, the data indicates that both statins are expected to competitively inhibit metazoan's HMGRs, and therefore all metazoan taxa might be at risk. The environmental relevance of these findings are discussed and research priorities established. We believe that the conceptual framework used in this study can be applied to other emerging pollutants and assist in the design of toxicity testing and risk assessment. PMID- 26896817 TI - Hepatobiliary and Pancreatic: Degenerative hepatic hemangioma mimicking biliary cystadenocarcinoma. PMID- 26896818 TI - Fibroblast growth factor 23 signaling in hippocampal cells: impact on neuronal morphology and synaptic density. AB - Endocrine fibroblast growth factor 23 (FGF23) is predominantly secreted by osteocytes and facilitates renal phosphate excretion. However, FGF23 is also present in cerebrospinal fluid. In chronic kidney disease, FGF23 serum levels are excessively elevated and associated with learning and memory deficits. Structural plasticity of the hippocampus such as formation of new synapses or an altered dendritic arborization comprises a cellular and morphological correlate of memory formation. Therefore, we hypothesize that FGF23 alters hippocampal neuron morphology and synapses. To address this, we prepared primary murine hippocampal cultures and incubated them with recombinant FGF23 alone or together with a soluble isoform of its co-receptor alpha-Klotho. Neuronal expression of a fluorescent reporter allowed for a detailed evaluation of the neuronal morphology by Sholl analysis. Additionally, we evaluated synaptic density, identified by stainings, for synaptic markers. We show an enhanced number of primary neurites combined with a reduced arborization, resulting in a less complex morphology of neurons treated with FGF23. Moreover, FGF23 enhances the synaptic density in a FGF-receptor (FGF-R) dependent manner. Finally, we addressed the corresponding signaling events downstream of FGF-R employing a combination of western blots and quantitative immunofluorescence. Interestingly, FGF23 induces phospholipase Cgamma activity in primary hippocampal neurons. Co-application of soluble alpha Klotho leads to activation of the Akt-pathway and modifies FGF23-impact on neuronal morphology and synaptic density. Compared with other FGFs, this alternative signaling pattern is a possible reason for differential effects of FGF23 on hippocampal neurons and may thereby contribute to learning and memory deficits in chronic kidney disease patients. In this study, we show that fibroblast growth factor 23 inhibits neuronal ramification and enhances the synaptic density in primary hippocampal cultures accompanied by phospholipase Cgamma-activation. Co-application of the co-receptor alpha-Klotho leads to an Akt activation and further modifies neuronal morphology and number of synapses. Those effects provide a mechanistic basis for memory deficits in patients suffering from chronic kidney disease (CKD) characterized by excessively elevated FGF23 levels as well as memory deficits. PMID- 26896821 TI - Social and ethical implications of fertility preservation. PMID- 26896820 TI - Clinical characterization of autoimmune LGI1 antibody limbic encephalitis. AB - OBJECTIVE: Autoimmune encephalitis associated with antibodies to leucine-rich glioma inactivated 1 (LGI1) has recently been identified and is characterized by an acute to subacute onset of cognitive impairment and convulsion, faciobrachial dystonic seizures (FBDSs), and psychiatric disturbances. This study analyzed the clinical characteristics and outcomes of 10 patients with LGI1 antibody encephalitis in order to further understand this disease and to improve its therapeutic strategies. METHODS: Between January 2013 and March 2015, we identified 10 patients with LGI1 antibody encephalitis. We retrospectively analyzed the clinical details, laboratory results, electrophysiological and imaging findings, and the treatment outcomes. RESULTS: All patients tested had LGI1 antibodies. Immunotherapy was effective in all patients. Seizures in patients with FBDS showed a poor response to antiepileptic drugs. Two patients examined by magnetoencephalogram (MEG) during the acute disease phase showed a small quantity of spike-wave dipoles in the temporal lobe close to the lateral fissure and insular lobe. CONCLUSION: Patients with LGI1 antibody encephalitis responded well to immunotherapy. We speculate that FBDS is likely a form of insular epilepsy. PMID- 26896819 TI - Palovarotene Inhibits Heterotopic Ossification and Maintains Limb Mobility and Growth in Mice With the Human ACVR1(R206H) Fibrodysplasia Ossificans Progressiva (FOP) Mutation. AB - Fibrodysplasia ossificans progressiva (FOP), a rare and as yet untreatable genetic disorder of progressive extraskeletal ossification, is the most disabling form of heterotopic ossification (HO) in humans and causes skeletal deformities, movement impairment, and premature death. Most FOP patients carry an activating mutation in a bone morphogenetic protein (BMP) type I receptor gene, ACVR1(R206H) , that promotes ectopic chondrogenesis and osteogenesis and, in turn, HO. We showed previously that the retinoic acid receptor gamma (RARgamma) agonist palovarotene effectively inhibited HO in injury-induced and genetic mouse models of the disease. Here we report that the drug additionally prevents spontaneous HO, using a novel conditional-on knock-in mouse line carrying the human ACVR1(R206H) mutation for classic FOP. In addition, palovarotene restored long bone growth, maintained growth plate function, and protected growing mutant neonates when given to lactating mothers. Importantly, palovarotene maintained joint, limb, and body motion, providing clear evidence for its encompassing therapeutic potential as a treatment for FOP. (c) 2016 American Society for Bone and Mineral Research. PMID- 26896822 TI - The leukotriene B4 receptor BLT2 protects barrier function via actin polymerization with phosphorylation of myosin phosphatase target subunit 1 in human keratinocytes. AB - Leukotriene B4 (LTB4 ) receptor type 2 (BLT2) is a novel G-protein-coupled receptor, which selectively binds to 12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT) with stronger affinity than to LTB4 . Recently, 12-HHT has been shown to have a protective effect on the epidermal barrier in human keratinocytes or transfectant cells overexpressing BLT2. Because the protective activity of BLT2 in high-calcium conditions, which occurs in well-differentiated cells, is exerted through increasing the integrity of tight junctions, we investigated the effects of 12-HHT on the barrier function of human keratinocytes in low-calcium conditions that mimic the basal layer; to our knowledge, this has not been reported previously. After stimulation with or without 12-HHT, barrier function was measured using transepithelial electrical resistance (TER) and dextran permeability assay. Expression levels of adhesion molecules and actin polymerization were also evaluated. Treatment with 12-HHT increased TER, along with decreased epidermal permeability of dextran in human keratinocytes. Furthermore, 12-HHT induced actin polymerization with phosphorylation of myosin phosphatase target subunit 1. These results suggest that the ligation of BLT2 protects permeability barrier function by enhancing cell-cell contact, even under low-calcium conditions, and indicate that a BLT2 agonist could be a novel therapeutic target for barrier-disrupted skin diseases. PMID- 26896823 TI - Ultrasonic waste activated sludge disintegration for recovering multiple nutrients for biofuel production. AB - Waste activated sludge is a valuable resource containing multiple nutrients, but is currently treated and disposed of as an important source of pollution. In this work, waste activated sludge after ultrasound pretreatment was reused as multiple nutrients for biofuel production. The nutrients trapped in sludge floc were transferred into liquid medium by ultrasonic disintegration during first 30 min, while further increase of pretreatment time only resulted in slight increase of nutrients release. Hydrogen production by Ethanoligenens harbinense B49 from glucose significantly increased with the concentration of ultrasonic sludge, and reached maximum yield of 1.97 mol H2/mol glucose at sludge concentration of 7.75 g volatile suspended solids/l. Without addition of any other chemicals, waste molasses rich in carbohydrate was efficiently turned into hydrogen with yield of 189.34 ml H2/g total sugar by E. harbinense B49 using ultrasonic sludge as nutrients. The results also showed that hydrogen production using pretreated sludge as multiple nutrients was higher than those using standard nutrients. Acetic acid produced by E. harbinense B49 together with the residual nutrients in the liquid medium were further converted into hydrogen (271.36 ml H2/g total sugar) by Rhodopseudomonas faecalis RLD-53 through photo fermentation, while ethanol was the sole end product with yield of 220.26 mg/g total sugar. Thus, pretreated sludge was an efficient nutrients source for biofuel production, which could replace the standard nutrients. This research provided a novel strategy to achieve environmental friendly sludge disposal and simultaneous efficient biofuel recovery from organic waste. PMID- 26896824 TI - Organic chloramines in drinking water: An assessment of formation, stability, reactivity and risk. AB - Although organic chloramines are known to form during the disinfection of drinking water with chlorine, little information is currently available on their occurrence or toxicity. In a recent in vitro study, some organic chloramines (e.g. N-chloroglycine) were found to be cytotoxic and genotoxic even at micromolar concentrations. In this paper, the formation and stability of 21 different organic chloramines, from chlorination of simple amines and amino acids, were studied, and the competition between 20 amino acids during chlorination was also investigated. For comparison, chlorination of two amides was also conducted. The formation and degradation of selected organic chloramines were measured using either direct UV spectroscopic or colorimetric detection. Although cysteine, methionine and tryptophan were the most reactive amino acids towards chlorination, they did not form organic chloramines at the chlorine to precursor molar ratios that were tested. Only 6 out of the 21 organic chloramines formed had a half-life of more than 3 h, although this group included all organic chloramines formed from amines. A health risk assessment relating stability and reactivity data from this study to toxicity and precursor abundance data from the literature indicated that only N-chloroglycine is likely to be of concern due to its stability, toxicity and abundance in water. However, given the stability of organic chloramines formed from amines, more information about the toxicity and precursor abundance for these chloramines is desirable. PMID- 26896825 TI - Postmolar choriocarcinoma: An independent risk factor for chemotherapy resistance in low-risk gestational trophoblastic neoplasia. AB - OBJECTIVE: To evaluate the effect of a clinicopathologic diagnosis of choriocarcinoma (CCA) on clinical characteristics, extent of disease, and response to chemotherapy in low-risk gestational trophoblastic neoplasia (GTN). METHODS: We reviewed the records of 678 patients with low-risk GTN (FIGO stage I and stages IIIII, score<7) treated from 1962 to 2009. Patient and disease characteristics, treatment course, as well as clinical response and survival were analyzed retrospectively. Patients with a clinicopathologic diagnosis of CCA were compared to those with a clinical diagnosis of postmolar GTN. RESULTS: Of 678 women with low-risk GTN, 129 (19.0%) had a clinicopathologic diagnosis of CCA. Patients with CCA had higher parity (median 1 vs. 0, p=0.003), more pretreatment human chorionic gonadotropin (hCG) levels at >100,000mIU/mL (12.7% vs. 5.9%, p=0.009), longer duration of disease (19.6 vs. 9.9weeks, p<0.001), and higher FIGO scores (median 2 vs. 1, p<0.001) compared with those with other histology; however, patients with CCA and postmolar GTN presented with similar stage of disease (stage I, 83.1% vs 88.2%, p=0.126). Although there was no difference in survival between groups, increased resistance to first-line methotrexate chemotherapy was significantly associated with a diagnosis of postmolar CCA (OR 2.67, p=0.007)), pretreatment hCG level at >10,000mIU/mL (OR 2.62, p=0.002), and higher FIGO score (3-4: OR 2.02, p=0.027; 5-6: OR 5.56, p<0.001) on multivariate analysis. CONCLUSIONS: Clinicopathologic diagnosis of postmolar CCA in patients with low-risk GTN is associated with higher pretreatment hCG levels, higher FIGO scores, and increased resistance to first-line single-agent methotrexate chemotherapy. PMID- 26896826 TI - Incorporating robotic-assisted surgery for endometrial cancer staging: Analysis of morbidity and costs. AB - OBJECTIVE: To evaluate how the introduction of robotic-assisted surgery affects treatment-related morbidity and cost of endometrial cancer (EC) staging. METHODS: We retrospectively reviewed the records of consecutive patients with stage I-III EC undergoing surgical staging between 2007 and 2012 at our institution. Costs (from surgery to 30days after surgery) were set based on the Medicare cost-to charge ratio for each year and inflated to 2014 values. Inverse probability weighting (IPW) was used to decrease the allocation bias when comparing outcomes between surgical groups. RESULTS: We focused our analysis on the 251 EC patients who had robotic-assisted surgery and the 384 who had open staging. During the study period, the use of robotic-assisted surgery increased and open staging decreased (P<0.001). Correcting group imbalances by using IPW methodology, we observed that patients undergoing robotic-assisted staging had a significantly lower postoperative complication rate, lower blood transfusion rate, longer median operating time, shorter median length of stay, and lower readmission rate than patients undergoing open staging (all P<0.001). Overall 30-day costs were similar between the 2 groups, with robotic-assisted surgery having significantly higher median operating room costs ($2820 difference; P<0.001) but lower median room and board costs ($2929 difference; P<0.001) than open surgery. Increasing experience with robotic-assisted staging was significantly associated with a decrease in median operating time (P=0.002) and length of stay (P=0.003). CONCLUSIONS: The implementation of robotic-assisted surgery for EC staging improves patient outcomes. It provides women the benefits of minimally invasive surgery without increasing costs and potentially improves patient turnover. PMID- 26896827 TI - Adjuvant radiation therapy in uterine carcinosarcoma: A population-based analysis of patient demographic and clinical characteristics, patterns of care and outcomes. AB - OBJECTIVE: To examine clinical and demographic characteristics of a population based cohort of patients with uterine carcinosarcoma (UCS), to assess access to treatment and survival patterns. METHODS: Surveillance, Epidemiology and End Results database was queried for patients diagnosed in 1999-2010 and treated with surgery with or without adjuvant radiation therapy (aRT). The Kaplan-Meier method was used to estimate survival functions, and Cox proportional hazards regression to analyze the effect of covariates on survival. RESULTS: 2342 patients were eligible. African Americans presented with more advanced AJCC stages than other races (35.4% vs. 29.1%; p<0.01). African Americans vs. others, and women diagnosed in 1999-2004 vs. in 2005-2010, received aRT at a similar rate: 36.5% vs. 39.9% (p=NS), and 39.5% vs. 38.9% (p=NS), respectively. There was a trend towards higher aRT utilization among patients younger than 65 vs. older (41.4% vs. 37.5%; p<0.06). We observed better overall and cause-specific survival in the aRT group: 42 vs. 22 (p<0.0001) and 57 vs. 28months (p<0.0001), respectively. Black race, diagnosis in 1999-2004, advanced stage and age>=65years carried a higher risk of UCS death. CONCLUSIONS: We observed greater survival rate in the aRT group. African Americans were more likely to present with later stage disease and die of UCS than non-African Americans. Age and stage, but not race, influenced receipt of aRT. Patients treated more recently survived longer. PMID- 26896829 TI - Energy cost and optimisation in breath-hold diving. AB - We present a new model for calculating locomotion costs in breath-hold divers. Starting from basic mechanics principles, we calculate the work that the diver must provide through propulsion to counterbalance the action of drag, the buoyant force and weight during immersion. Compared to those in previous studies, the model presented here accurately analyses breath-hold divers which alternate active swimming with prolonged glides during the dive (as is the case in mammals). The energy cost of the dive is strongly dependent on these prolonged gliding phases. Here we investigate the length and impacts on energy cost of these glides with respect to the diver characteristics, and compare them with those observed in different breath-hold diving species. Taking into account the basal metabolic rate and chemical energy to propulsion transformation efficiency, we calculate optimal swim velocity and the corresponding total energy cost (including metabolic rate) and compare them with observations. Energy cost is minimised when the diver passes through neutral buoyancy conditions during the dive. This generally implies the presence of prolonged gliding phases in both ascent and descent, where the buoyancy (varying with depth) is best used against the drag, reducing energy cost. This is in agreement with past results (Miller et al., 2012; Sato et al., 2013) where, when the buoyant force is considered constant during the dive, the energy cost was minimised for neutral buoyancy. In particular, our model confirms the good physical adaption of dolphins for diving, compared to other breath-hold diving species which are mostly positively buoyant (penguins for example). The presence of prolonged glides implies a non-trivial dependency of optimal speed on maximal depth of the dive. This extends previous findings (Sato et al., 2010; Watanabe et al., 2011) which found no dependency of optimal speed on dive depth for particular conditions. The energy cost of the dive can be further diminished by reducing the volume of gas-filled body parts in divers close to neutral buoyancy. This provides a possible additional explanation for the observed exhalation of air before diving in phocid seals to minimise dive energy cost. Until now the only explanation for this phenomenon has been a reduction in the risk of decompression sickness. PMID- 26896830 TI - Respiratory infections associated with enterovirus D68 from 2011 to 2015 in Beijing, China. AB - Enterovirus D68 (EV-D68) is an emergent viral pathogen associated with mild to severe respiratory infections. In this study, we describe respiratory infections associated with EV-D68 in Beijing over a 4 year period. Total nucleic acid was extracted from 7,945 clinical specimens collected between January 5, 2011 and July 30, 2015 in Beijing and used for detecting EV-D68 and other enteroviruses by real-time PCR. Overall, 555/7,945 (6.99%) specimens were enterovirus positive: 12/7,945 (0.2%) specimens were EV-D68 positive. Of these patients, 11 were pediatric patients and 1 was a 76-year-old man. The main symptoms for the 12 EV D68 positive patients were fever (10/12, 83.3%) and cough (6/12, 50%). Ten EV-D68 infection cases were identified in autumn or winter season. The phylogenetic relationships of the 12 EV-D68 viral strains with other strains were analyzed based on the sequences of viral protein 1(VP1). The EV-D68 strains from 2011 to 2013 belonged to groups 1 or 3, while all strains in 2014 were clustered into group 1 together with the strains circulating in the USA. In conclusion, EV-D68 played a role in respiratory infections in Beijing during this period. In addition, the most common EV-D68 strain detected was similar to that circulating in the USA in 2014. J. Med. Virol. 88:1529-1534, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26896831 TI - The correlation between miR-146a C/G polymorphism and UHRF1 gene expression level in gastric tumor. AB - OBJECTIVE: To investigate the association between the polymorphism of miR-146a and The ubiquitin-like with PHD and ring-finger domains 1 (UHRF1) expression in patients with gastric cancer. METHODS: MiR-146a rs2910164 was genotyped in 130 patients with gastric cancer and 130 cancer-free individuals using polymerase chain reaction (PCR)-restriction fragment length polymorphism. UHRF1 expression was analyzed in 22 gastric cancer tissues and their adjacent normal tissues using quantitative real-time PCR. RESULTS: No significant differences in genotype distributions of miR-146a rs2910164 were found between cases and controls, but we observed that grade II tumors were more frequently detected in patients with CG/CC genotype compared to those with CC genotype. UHRF1 expressions in cancerous tissues were significantly higher than in noncancerous tissues (1.89-fold). Patients with CC genotype showed a significant increase in UHRF1 expression in comparison to the carriers of GG/CG genotype. A higher UHRF1 expression was associated with cancer stage IV and grade III (P<0.05). CONCLUSION: The overexpression of UHRF1 was correlated with the stage and grade of gastric cancer and is associated with the genotype distribution of rs2910164. PMID- 26896828 TI - Population pharmacokinetic and pharmacodynamic analysis of BIIB023, an anti-TNF like weak inducer of apoptosis (anti-TWEAK) monoclonal antibody. AB - AIMS: Tumour necrosis factor-like weak inducer of apoptosis (TWEAK) is implicated in the pathogenesis of lupus nephritis. This study evaluated the pharmacokinetics, using the population approach, and pharmacodynamics of BIIB023, an anti-TWEAK monoclonal antibody, in healthy Chinese, Japanese and Caucasian volunteers. METHODS: In this single-dose, randomized, double-blind, phase 1 study of BIIB023 in healthy volunteers, BIIB023 was administered by intravenous infusion (3 or 20 mg kg(-1) ) on Day 1; follow-up occurred through Day 71. BIIB023 serum concentration was measured using a validated enzyme-linked immunosorbent assay; BIIB023 concentration-time data were subjected to noncompartmental analysis. Population pharmacokinetic analysis was performed using data from this study and a prior phase 1 study of BIIB023 in subjects with rheumatoid arthritis. Soluble TWEAK and TWEAK: BIIB023 complex were evaluated. RESULTS: There were no differences in BIIB023 pharmacokinetics requiring dose adjustment among the three ethnic groups or between healthy volunteers and arthritis patients. BIIB023 central compartment volume (3050 ml) and clearance (7.42 ml h(-1) ) were comparable to those observed for other monoclonal antibody drugs. BIIB023 serum exposure increased in a dose-dependent manner in all groups, but not in direct proportion to dose level; at concentrations below ~10 MUg ml( 1) , nonlinear clearance was observed. Soluble TWEAK levels decreased to below the level of quantitation after BIIB023 treatment, with concomitant changes in TWEAK: BIIB023 complex levels. CONCLUSIONS: No clinically meaningful differences were observed in BIIB023 pharmacokinetic and pharmacodynamic properties in healthy Chinese, Japanese and Caucasian volunteers; pharmacodynamic measures suggested target engagement. TWEAK may be an attractive therapeutic target for lupus nephritis treatment. PMID- 26896832 TI - Rho kinase inhibition following traumatic brain injury in mice promotes functional improvement and acute neuron survival but has little effect on neurogenesis, glial responses or neuroinflammation. AB - Inhibition of the Rho/Rho kinase pathway has been shown to be beneficial in a variety of neural injuries and diseases. In this manuscript we investigate the role of Rho kinase inhibition in recovery from traumatic brain injury using a controlled cortical impact model in mice. Mice subjected to a moderately severe TBI were treated for 1 or 4 weeks with the Rho kinase inhibitor Y27632, and functional outcomes and neuronal and glial cell responses were analysed at 1, 7 and 35 days post-injury. We hypothesised that Y27632-treated mice would show functional improvement, with augmented recruitment of neuroblasts from the SVZ and enhanced survival of newborn neurons in the pericontusional cortex, with protection against neuronal degeneration, neuroinflammation and modulation of astrocyte reactivity and blood-brain-barrier permeability. While Rho kinase inhibition enhanced recovery of motor function after trauma, there were no substantial increases in the recruitment of DCX(+) neuroblasts or the number of BrdU(+) or EdU(+) labelled newborn neurons in the pericontusional cortex of Y27632-treated mice. Inhibition of Rho kinase significantly reduced the number of degenerating cortical neurons at 1day post-injury compared to saline controls but had no longer term effect on neuronal degeneration, with only modest effects on astrocytic reactivity and macrophage/microglial responses. Overall, this study showed that Rho kinase contributes to acute neurodegenerative processes in the injured cortex but does not play a significant role in SVZ neural precursor cell derived adult neurogenesis, glial responses or blood-brain barrier permeability following a moderately severe brain injury. PMID- 26896833 TI - Long-term consequences of conditional genetic deletion of PTEN in the sensorimotor cortex of neonatal mice. AB - Targeted deletion of the phosphatase and tensin homolog on chromosome ten (PTEN) gene in the sensorimotor cortex of neonatal mice enables robust regeneration of corticospinal tract (CST) axons following spinal cord injury as adults. Here, we assess the consequences of long-term conditional genetic PTEN deletion on cortical structure and neuronal morphology and screen for neuropathology. Mice with a LoxP-flanked exon 5 of the PTEN gene (PTENf/f mice) received AAV-Cre injections into the sensorimotor cortex at postnatal day 1 (P1) and were allowed to survive for up to 18months. As adults, mice were assessed for exploratory activity (open field), and motor coordination using the Rotarod(r). Some mice received injections of Fluorogold into the spinal cord to retrogradely label the cells of origin of the CST. Brains were prepared for neurohistology and immunostained for PTEN and phospho-S6, which is a downstream marker of mammalian target of rapamycin (mTOR) activation. Immunostaining revealed a focal area of PTEN deletion affecting neurons in all cortical layers, although in some cases PTEN expression was maintained in many small-medium sized neurons in layers III IV. Neurons lacking PTEN were robustly stained for pS6. Cortical thickness was significantly increased and cortical lamination was disrupted in the area of PTEN deletion. PTEN-negative layer V neurons that give rise to the CST, identified by retrograde labeling, were larger than neurons with maintained PTEN expression, and the relative area occupied by neuropil vs. cell bodies was increased. There was no evidence of tumor formation or other neuropathology. Mice with PTEN deletion exhibited open field activity comparable to controls and there was a trend for impaired Rotarod performance (not statistically significant). Our findings indicate that early postnatal genetic deletion of PTEN that is sufficient to enable axon regeneration by adult neurons causes neuronal hypertrophy but no other detectable neuropathology. PMID- 26896835 TI - Responses to sodium dodecyl sulphate as an in vivo human model to study the pathomechanisms underlying sensitive skin. PMID- 26896836 TI - Validating the plate mapping method: Comparing drawn foods and actual foods of university students in a cafeteria. AB - To examine effects of plate size on meals, I developed a method I label plate mapping. To validate plate mapping, a quasi-experimental between participants study was conducted that asked university students to accurately draw their lunch meal. Participants were randomized into groups where they were asked either pre consumption or post-consumption to draw their lunch on either a 9" or 11" paper plate. Coding plate drawings for total meal size revealed that students drew bigger meals on larger plates and participant meal size drawings were more accurate when the plate provided was the same size as the meal plate used. Gender moderated meal size drawings, with women generally drawing meals that were more highly correlated and similarly sized to actual meals when compared to the drawings of men. Overall, the size of plate drawings was highly correlated with the size of actual foods, which provides support for the validity of the method of plate mapping. These findings suggest that plate mapping can be applied to estimate meal size and assess sensitivity to plate size. Gaining a better understanding of the mechanisms and processes that influence food consumption habits can help increase awareness of these cues for both academics as well as for consumers of food and benefit short- and long-term health goals. PMID- 26896837 TI - Eating behaviours in preadolescence are associated with body dissatisfaction and mental disorders - Results of the CCC2000 study. AB - Preadolescence is a key period in the early stages of eating disorder development. The aim of the present study was, firstly, to investigate restrained, emotional and external eating in a general population-based sample of 11-12 year olds. Secondly, we sought to explore how these eating behaviours are associated with possible predictors of eating disorders, such as body dissatisfaction, weight status and mental disorders. A subsample of 1567 children (47.7% boys; 52.3% girls) from the Copenhagen Child Cohort (CCC2000) completed web-based questionnaires on eating behaviours and body dissatisfaction using The Eating Pattern Inventory for Children (EPI-C) and The Children's Figure Rating Scale. Mental disorders were assessed using the online version of the Development and Well-Being Assessment (DAWBA) based on parental replies with final DSM-IV diagnoses determined by experienced child- and adolescent psychiatrists. Height and weight were measured at a face-to-face assessment. The results showed that restrained eating was significantly associated with overweight, body dissatisfaction and emotional disorders in both genders. Emotional eating showed similar associations with overweight and body dissatisfaction in both genders, but was only associated with mental disorders in girls. External eating was significantly associated with body dissatisfaction and neurodevelopmental disorders in both genders, but was only associated with overweight in girls. Our findings show that problematic eating behaviours can be identified in preadolescence, and co-exist with weight problems and mental disorders. Thus restrained, emotional and external eating was, in different ways, associated with overweight, body dissatisfaction and mental disorders. Our findings point to significant eating behaviours in preadolescence, which could constitute potential predictors of later eating disorder risk. PMID- 26896838 TI - Follicle cell trypsin-like protease HrOvochymase: Its cDNA cloning, localization, and involvement in the late stage of oogenesis in the ascidian Halocynthia roretzi. AB - We previously reported that the sperm trypsin-like protease HrAcrosin and its precursor HrProacrosin participate in fertilization of the ascidian Halocynthia roretzi. The HrProacrosin gene is annotated in the H. roretzi genome database as Harore.CG.MTP2014.S89.g15383; our previously reported sequence of HrProacrosin gene appeared to include four nucleotides inserted near the 3'-end of HrProacrosin, resulting in a frame-shift mutation and a premature termination codon. The gene architecture of HrProacrosin and Harore.CG.MTP2014.S89.g15383 resembles that of Xenopus laevis ovochymase-1/OVCH1 and ovochymase-2/OVCH2, which encode egg extracellular polyproteases. Considering these new observations, we evaluated the cDNA cloning, expression, localization, and function of Harore.CG.MTP2014.S89.g15383, herein designated as HrOvochymase/HrOVCH. We found that HrOVCH cDNA consists of a single open reading frame of 1,575 amino acids, containing a signal peptide, three trypsin-like protease domains, and six CUB domains. HrOVCH was transcribed by the testis and ovary, but the majority of protein exists in ovarian follicle cells surrounding eggs. An anti-HrOVCH antibody inhibited elevation of the vitelline coat at a late stage of oogenesis, during the period when self-sterility is acquired. As trypsin inhibitors are reported to block the acquisition of self-sterility during oogenesis, whereas trypsin induces the acquisition of self-sterility and elevation of the vitelline coat in defolliculated ovarian eggs, we propose that HrOVCH may play a role in the acquisition of self-sterility by late-stage H. roretzi oocytes. PMID- 26896834 TI - Repeated low-dose kainate administration in C57BL/6J mice produces temporal lobe epilepsy pathology but infrequent spontaneous seizures. AB - More efficient or translationally relevant approaches are needed to model acquired temporal lobe epilepsy (TLE) in genetically tractable mice. The high costs associated with breeding and maintaining transgenic, knock-in, or knock-out lines place a high value on the efficiency of induction and animal survivability. Herein, we describe our approaches to model acquired epilepsy in C57BL/6J mice using repeated, low-dose kainate (KA) administration paradigms. Four paradigms (i.p.) were tested for their ability to induce status epilepticus (SE), temporal lobe pathology, and the development of epilepsy. All four paradigms reliably induce behavioral and/or electrographic SE without mortality over a 7d period. Two of the four paradigms investigated produce features indicative of TLE pathology, including hippocampal cell death, widespread astrogliosis, and astrocyte expression of mGluR5, a feature commonly reported in TLE models. Three of the investigated paradigms were able to produce aberrant electrographic features, such as interictal spiking in cortex. However, only one paradigm, previously published by others, produces spontaneous recurrent seizures over an eight week period. Presentation of spontaneous seizures is rare (N=2/14), with epilepsy preferentially developing in animals having a high number of seizures during SE. Overall, repeated, low-dose KA administration improves the efficiency and pathological relevance of a systemic KA insult, but does not produce a robust epilepsy phenotype under the experimental paradigms described herein. PMID- 26896840 TI - Revealing the potential of Didodecyldimethylammonium bromide as efficient scaffold for fabrication of nano liquid crystalline structures. AB - To exploit the potential of Didodecyldimethylammonium bromide (D12DAB) as a core lipidic constituent, an attempt was made to fabricate and optimize cationic nanostructured lipid carriers (cNLCs) using a cost-effective microemulsification methodology. Designed composition was optimized by studying the effect of different microemulsion components on D12DAB cNLCs characteristics. Spherical shaped D12DAB cNLCs were obtained with an average size of ~160 nm and zeta potential of +30.2 mV. Differential Scanning Calorimetry (DSC) depicted the presence of thermotropic character, whereas polarized optical microscopy confirmed the mesophase like behavior of D12DAB based cNLCs. In addition, hemolysis analysis revealed that the toxicity was concentration dependent as LC50 was reached at a concentration of 50 MUg/mL of cNLCs. This class of cNLCs is expected to become a potent candidate for a broad spectrum of medicaments as carriers, targeting for pharmaceutical and medicinal purposes, due to the combination of a hard lipid with a soft lipid, where the liquid crystalline structure of the lipid co-exists. PMID- 26896839 TI - Stimuli responsive charge-switchable lipids: Capture and release of nucleic acids. AB - Stimuli responsive lipids, which enable control over the formation, transformation, and disruption of supramolecular assemblies, are of interest for biosensing, diagnostics, drug delivery, and basic transmembrane protein studies. In particular, spatiotemporal control over a supramolecular structure can be achieved using light activated compounds to induce significant supramolecular rearrangements. As such, a family of cationic lipids are described which undergo a permanent switch in charge upon exposure to 365 nm ultraviolet (UV) light to enable the capture of negatively charged nucleic acids within the self-assembled supramolecular structure of the lipids and subsequent release of these macromolecules upon exposure to UV light and disruption of the assemblies. The lipids are composed of either two different tripeptide head groups, Lysine Glycine-Glycine (KGG) and Glycine-Glycine-Glycine (GGG) and three different hydrocarbon chain lengths (C6, C10, or C14) terminated by a UV light responsive 1 (2-nitrophenyl)ethanol (NPE) protected carboxylic acid. The photolysis of the NPE protected lipid is measured as a function of time, and the resulting changes in net molecular charge are observed using zeta potential analysis for each head group and chain length combination. A proof of concept study for the capture and release of both linear DNA (calf thymus) and siRNA is presented using an ethidium bromide quenching assay where a balance between binding affinity and supramolecular stability are found to be the key to optimal nucleic acid capture and release. PMID- 26896842 TI - Takotsubo syndrome caused by subconjunctival injection of a mydricaine analogue. PMID- 26896841 TI - Progressive cell-mediated changes in articular cartilage and bone in mice are initiated by a single session of controlled cyclic compressive loading. AB - We previously showed that repetitive cyclic loading of the mouse knee joint causes changes that recapitulate the features of osteoarthritis (OA) in humans. By applying a single loading session, we characterized the temporal progression of the structural and compositional changes in subchondral bone and articular cartilage. We applied loading during a single 5-minute session to the left tibia of adult (26-week-old) C57Bl/6 male mice at a peak load of 9.0N for 1,200 cycles. Knee joints were collected at times 0, 1, and 2 weeks after loading. The changes in articular cartilage and subchondral bone were analyzed by histology, immunohistochemistry (caspase-3 and cathepsin K), and microcomputed tomography. At time 0, no change was evident in chondrocyte viability or cartilage or subchondral bone integrity. However, cartilage pathology demonstrated by localized thinning and proteoglycan loss occurred at 1 and 2 weeks after the single session of loading. Transient cancellous bone loss was evident at 1 week, associated with increased osteoclast number. Bone loss was reversed to control levels at 2 weeks. We observed formation of fibrous and cartilaginous tissues at the joint margins at 1 and 2 weeks. Our findings demonstrate that a single session of noninvasive loading leads to the development of OA-like morphological and cellular alterations in articular cartilage and subchondral bone. The loss in subchondral trabecular bone mass and thickness returns to control levels at 2 weeks, whereas the cartilage thinning and proteoglycan loss persist. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1941-1949, 2016. PMID- 26896843 TI - Molecular cloning and pharmacological characterization of giant panda (Ailuropoda melanoleuca) melanocortin-4 receptor. AB - The melanocortin-4 receptor (MC4R) is critical in regulating mammalian food intake and energy expenditure. Giant panda (Ailuropoda melanoleuca), famous as the living fossil, is an endangered species endemic to China. We are interested in exploring the functions of the giant panda MC4R (amMC4R) in regulating energy homeostasis and report herein the molecular cloning and pharmacology of the amMC4R. Sequence analysis revealed that amMC4R was highly homologous (>88%) at nucleotide and amino acid sequences to several mammalian MC4Rs. Western blot revealed that the expression construct myc-amMC4R in pcDNA3.1 was successfully constructed and expressed in HEK293T cells. With human MC4R (hMC4R) as a control, pharmacological characteristics of amMC4R were analyzed with binding and signaling assays. Four agonists, including [Nle(4), D-Phe(7)]-alpha-melanocyte stimulating hormone (NDP-MSH), alpha- and beta-MSH, and a small molecule agonist, THIQ, were used in binding and signaling assays. We showed that amMC4R bound NDP MSH with the highest affinity followed by THIQ, alpha-MSH, and beta-MSH, with the same ranking order as hMC4R. Treatment of HEK293T cells expressing amMC4R with different concentrations of agonists resulted in dose-dependent increase of intracellular cAMP levels, with similar EC50s for the four agonists. The results suggested that the cloned amMC4R encoded a functional MC4R. The availability of amMC4R and its binding and signaling properties will facilitate the investigation of amMC4R in regulating food intake and energy homeostasis. PMID- 26896844 TI - EXTRACT: interactive extraction of environment metadata and term suggestion for metagenomic sample annotation. AB - The microbial and molecular ecology research communities have made substantial progress on developing standards for annotating samples with environment metadata. However, sample manual annotation is a highly labor intensive process and requires familiarity with the terminologies used. We have therefore developed an interactive annotation tool, EXTRACT, which helps curators identify and extract standard-compliant terms for annotation of metagenomic records and other samples. Behind its web-based user interface, the system combines published methods for named entity recognition of environment, organism, tissue and disease terms. The evaluators in the BioCreative V Interactive Annotation Task found the system to be intuitive, useful, well documented and sufficiently accurate to be helpful in spotting relevant text passages and extracting organism and environment terms. Comparison of fully manual and text-mining-assisted curation revealed that EXTRACT speeds up annotation by 15-25% and helps curators to detect terms that would otherwise have been missed. Database URL: https://extract.hcmr.gr/. PMID- 26896845 TI - The UniProtKB guide to the human proteome. AB - Advances in high-throughput and advanced technologies allow researchers to routinely perform whole genome and proteome analysis. For this purpose, they need high-quality resources providing comprehensive gene and protein sets for their organisms of interest. Using the example of the human proteome, we will describe the content of a complete proteome in the UniProt Knowledgebase (UniProtKB). We will show how manual expert curation of UniProtKB/Swiss-Prot is complemented by expert-driven automatic annotation to build a comprehensive, high-quality and traceable resource. We will also illustrate how the complexity of the human proteome is captured and structured in UniProtKB. Database URL: www.uniprot.org. PMID- 26896846 TI - NALDB: nucleic acid ligand database for small molecules targeting nucleic acid. AB - Nucleic acid ligand database (NALDB) is a unique database that provides detailed information about the experimental data of small molecules that were reported to target several types of nucleic acid structures. NALDB is the first ligand database that contains ligand information for all type of nucleic acid. NALDB contains more than 3500 ligand entries with detailed pharmacokinetic and pharmacodynamic information such as target name, target sequence, ligand 2D/3D structure, SMILES, molecular formula, molecular weight, net-formal charge, AlogP, number of rings, number of hydrogen bond donor and acceptor, potential energy along with their Ki, Kd, IC50 values. All these details at single platform would be helpful for the development and betterment of novel ligands targeting nucleic acids that could serve as a potential target in different diseases including cancers and neurological disorders. With maximum 255 conformers for each ligand entry, our database is a multi-conformer database and can facilitate the virtual screening process. NALDB provides powerful web-based search tools that make database searching efficient and simplified using option for text as well as for structure query. NALDB also provides multi-dimensional advanced search tool which can screen the database molecules on the basis of molecular properties of ligand provided by database users. A 3D structure visualization tool has also been included for 3D structure representation of ligands. NALDB offers an inclusive pharmacological information and the structurally flexible set of small molecules with their three-dimensional conformers that can accelerate the virtual screening and other modeling processes and eventually complement the nucleic acid-based drug discovery research. NALDB can be routinely updated and freely available on bsbe.iiti.ac.in/bsbe/naldb/HOME.php. Database URL: http://bsbe.iiti.ac.in/bsbe/naldb/HOME.php. PMID- 26896848 TI - MGFD: the maize gene families database. AB - Most gene families are transcription factor (TF) families, which have fundamental roles in almost all biological processes (development, growth and response to environmental factors) and have been employed to manipulate various types of metabolic, developmental and stress response pathways in plants. Maize (Zea mays) is one of the most important cereal crops in the world due its importance to human nutrition and health. Thus, identifying and annotating all the gene families in maize is an important primary step in defining their functions and understanding their roles in the regulation of diverse biological processes. In this study, we identified 96 predicted maize gene families and systematically characterized all 5826 of the genes in those families. We have also developed a comprehensive database of maize gene families (the MGFD). To further explore the functions of these gene families, we extensively annotated the genes, including such basic information as protein sequence features, gene structure, Gene Ontology classifications, phylogenetic relationships and expression profiles. The MGFD has a user-friendly web interface with multiple browse and search functions, as well as data downloading. The MGFD is freely available to users at http://mgfd.ahau.edu.cn/. Database URL: http://mgfd.ahau.edu.cn/. PMID- 26896850 TI - Decreased glycolate oxidase activity leads to altered carbon allocation and leaf senescence after a transfer from high CO2 to ambient air in Arabidopsis thaliana. AB - Metabolic and physiological analyses of Arabidopsis thaliana glycolate oxidase (GOX) mutant leaves were performed to understand the development of the photorespiratory phenotype after transfer from high CO2 to air. We show that two Arabidopsis genes, GOX1 and GOX2, share a redundant photorespiratory role. Air grown single gox1 and gox2 mutants grew normally and no significant differences in leaf metabolic levels and photosynthetic activities were found when compared with wild-type plants. To study the impact of a highly reduced GOX activity on plant metabolism, both GOX1 and GOX2 expression was knocked-down using an artificial miRNA strategy. Air-grown amiRgox1/2 plants with a residual 5% GOX activity exhibited a severe growth phenotype. When high-CO2-grown adult plants were transferred to air, the photosynthetic activity of amiRgox1/2 was rapidly reduced to 50% of control levels, and a high non-photochemical chlorophyll fluorescence quenching was maintained. (13)C-labeling revealed that daily assimilated carbon accumulated in glycolate, leading to reduced carbon allocation to sugars, organic acids, and amino acids. Such changes were not always mirrored in leaf total metabolite levels, since many soluble amino acids increased after transfer, while total soluble protein, RuBisCO (ribulose-1,5-bisphosphate carboxylase/oxygenase), and chlorophyll amounts decreased in amiRgox1/2 plants. The senescence marker, SAG12, was induced only in amiRgox1/2 rosettes after transfer to air. The expression of maize photorespiratory GOX in amiRgox1/2 abolished all observed phenotypes. The results indicate that the inhibition of the photorespiratory cycle negatively impacts photosynthesis, alters carbon allocation, and leads to early senescence in old rosette leaves. PMID- 26896849 TI - Characterization of a JAZ7 activation-tagged Arabidopsis mutant with increased susceptibility to the fungal pathogen Fusarium oxysporum. AB - In Arabidopsis, jasmonate (JA)-signaling plays a key role in mediating Fusarium oxysporum disease outcome. However, the roles of JASMONATE ZIM-domain (JAZ) proteins that repress JA-signaling have not been characterized in host resistance or susceptibility to this pathogen. Here, we found most JAZ genes are induced following F. oxysporum challenge, and screening T-DNA insertion lines in Arabidopsis JAZ family members identified a highly disease-susceptible JAZ7 mutant (jaz7-1D). This mutant exhibited constitutive JAZ7 expression and conferred increased JA-sensitivity, suggesting activation of JA-signaling. Unlike jaz7 loss-of-function alleles, jaz7-1D also had enhanced JA-responsive gene expression, altered development and increased susceptibility to the bacterial pathogen PstDC3000 that also disrupts host JA-responses. We also demonstrate that JAZ7 interacts with transcription factors functioning as activators (MYC3, MYC4) or repressors (JAM1) of JA-signaling and contains a functional EAR repressor motif mediating transcriptional repression via the co-repressor TOPLESS (TPL). We propose through direct TPL recruitment, in wild-type plants JAZ7 functions as a repressor within the JA-response network and that in jaz7-1D plants, misregulated ectopic JAZ7 expression hyper-activates JA-signaling in part by disturbing finely tuned COI1-JAZ-TPL-TF complexes. PMID- 26896847 TI - Ensembl comparative genomics resources. AB - Evolution provides the unifying framework with which to understand biology. The coherent investigation of genic and genomic data often requires comparative genomics analyses based on whole-genome alignments, sets of homologous genes and other relevant datasets in order to evaluate and answer evolutionary-related questions. However, the complexity and computational requirements of producing such data are substantial: this has led to only a small number of reference resources that are used for most comparative analyses. The Ensembl comparative genomics resources are one such reference set that facilitates comprehensive and reproducible analysis of chordate genome data. Ensembl computes pairwise and multiple whole-genome alignments from which large-scale synteny, per-base conservation scores and constrained elements are obtained. Gene alignments are used to define Ensembl Protein Families, GeneTrees and homologies for both protein-coding and non-coding RNA genes. These resources are updated frequently and have a consistent informatics infrastructure and data presentation across all supported species. Specialized web-based visualizations are also available including synteny displays, collapsible gene tree plots, a gene family locator and different alignment views. The Ensembl comparative genomics infrastructure is extensively reused for the analysis of non-vertebrate species by other projects including Ensembl Genomes and Gramene and much of the information here is relevant to these projects. The consistency of the annotation across species and the focus on vertebrates makes Ensembl an ideal system to perform and support vertebrate comparative genomic analyses. We use robust software and pipelines to produce reference comparative data and make it freely available. Database URL: http://www.ensembl.org. PMID- 26896852 TI - Developmental patterning and segregation of alkaloids in areca nut (seed of Areca catechu) revealed by magnetic resonance and mass spectrometry imaging. AB - Areca nut (seed of Areca catechu) is consumed by people from different parts of Asia, including India. The four major alkaloids present in areca nut are arecoline, arecaidine, guvacoline and guvacine. Upon cutting, the nut reveals two kinds of regions; white and brown. In our present study, we have monitored the formation of these two regions within the nut during maturation, using the non invasive techniques of magnetic resonance imaging (MRI) and volume localized magnetic resonance spectroscopy (MRS). Electrospray ionization mass spectrometry (ESI MS) and desorption electrospray ionization mass spectrometry (DESI MS) imaging have been used to study the associated change in the alkaloid contents of these two regions during the growth of the nut. Our study reveals that white and brown regions start forming within the nut when the liquid within starts solidifying. At the final stage of maturity, arecoline, arecaidine and guvacoline get segregated in the brown region whereas guvacine gets to the white region of the nut. The transport of molecules with maturity and corresponding pattern formation are expected to be associated with a multitude of physiochemical changes. PMID- 26896851 TI - Comparative cell-specific transcriptomics reveals differentiation of C4 photosynthesis pathways in switchgrass and other C4 lineages. AB - Almost all C4 plants require the co-ordination of the adjacent and fully differentiated cell types, mesophyll (M) and bundle sheath (BS). The C4 photosynthetic pathway operates through two distinct subtypes based on how malate is decarboxylated in BS cells; through NAD-malic enzyme (NAD-ME) or NADP-malic enzyme (NADP-ME). The diverse or unique cell-specific molecular features of M and BS cells from separate C4 subtypes of independent lineages remain to be determined. We here provide an M/BS cell type-specific transcriptome data set from the monocot NAD-ME subtype switchgrass (Panicum virgatum). A comparative transcriptomics approach was then applied to compare the M/BS mRNA profiles of switchgrass, monocot NADP-ME subtype C4 plants maize and Setaria viridis, and dicot NAD-ME subtype Cleome gynandra. We evaluated the convergence in the transcript abundance of core components in C4 photosynthesis and transcription factors to establish Kranz anatomy, as well as gene distribution of biological functions, in these four independent C4 lineages. We also estimated the divergence between NAD-ME and NADP-ME subtypes of C4 photosynthesis in the two cell types within C4 species, including differences in genes encoding decarboxylating enzymes, aminotransferases, and metabolite transporters, and differences in the cell-specific functional enrichment of RNA regulation and protein biogenesis/homeostasis. We suggest that C4 plants of independent lineages in both monocots and dicots underwent convergent evolution to establish C4 photosynthesis, while distinct C4 subtypes also underwent divergent processes for the optimization of M and BS cell co-ordination. The comprehensive data sets in our study provide a basis for further research on evolution of C4 species. PMID- 26896853 TI - Systematic review of differential inorganic arsenic exposure in minority, low income, and indigenous populations in the United States. AB - Inorganic arsenic (iAs) is a human carcinogen and associated with cardiovascular, respiratory, and skin diseases. Natural and anthropogenic sources contribute to low concentrations of iAs in water, food, soil, and air. Differential exposure to environmental hazards in minority, indigenous, and low income populations is considered an environmental justice (EJ) concern, yet it is unclear if higher iAs exposure occurs in these populations. A systematic review was conducted to evaluate evidence for differential iAs exposure in the United States (US). The peer-reviewed literature was searched for studies that (1) estimated iAs exposure based on environmental concentrations of iAs in water, food, soil, or iAs biomarkers and (2) examined iAs exposure in minority, indigenous, and low income US populations. Five studies were identified that estimated exposures and provided demographic information about EJ populations. These studies reported arsenic concentrations in water, soil, or food to estimate exposure, with varied evidence of differential exposure. Additionally, six studies were identified that suggested potential arsenic exposure from environmental sources including soil, rice, private well-water, and fish, but did not report data stratified by demographic information. Evidence across these 11 studies was qualitatively integrated to draw conclusions about differential iAs exposure. The total body of evidence is limited by lack of individual exposure measures, lack of iAs concentration data, and insufficient comparative demographic data. Based upon these data gaps, there is inadequate evidence to conclude whether differential exposure to iAs is an EJ concern in the US. PMID- 26896854 TI - Systematic reviews on neurodevelopmental and neurodegenerative disorders linked to pesticide exposure: Methodological features and impact on risk assessment. AB - BACKGROUND: Epidemiological data are not currently used in the risk assessment of chemical substances in a systematic and consistent manner. However, systematic reviews (SRs) could be useful for risk assessment as they appraise and synthesize the best epidemiological knowledge available. OBJECTIVES: To conduct a comprehensive literature search of SRs pertaining to pesticide exposure and various neurological outcomes, namely neurodevelopmental abnormalities, Parkinson's disease (PD) and Alzheimer's disease (AD), and to assess the potential contribution of SRs to the risk assessment process. SEARCH METHODS AND SELECTION CRITERIA: Search was conducted in PubMed and Web of Science databases and articles were selected if the following inclusion criteria were met: being a SR, published until April 2015 and without language restrictions. DATA COLLECTION AND ANALYSIS: For each neurological outcome, two review authors independently screened the search results for included studies. Data were extracted and summarized in two tables according to 16 criteria. Disagreements were resolved by discussion. MAIN RESULTS: The total number of studies identified in the first search was 65, 304 and 108 for neurodevelopment, PD and AD, respectively. From them, 8, 10 and 2 met the defined inclusion criteria for those outcomes, respectively. Overall, results suggest that prenatal exposure to organophosphates is associated with neurodevelopmental disturbances in preschool and school children. In contrast, postnatal exposures failed to show a clear effect across cohort studies. Regarding PD, 6 SRs reported statistically significant combined effect size estimates, with OR/RR ranging between 1.28 and 1.94. As for AD, 2 out of the 8 original articles included in the SRs found significant associations, with OR of 2.39 and 4.35, although the quality of the data was rather low. CONCLUSIONS: The critical appraisal of the SRs identified allowed for discussing the implications of SRs for risk assessment, along with the identification of gaps and limitations of current epidemiological studies that hinder their use for risk assessment. Recommendations are proposed to improve studies for this purpose. In particular, harmonized quantitative data (expressed in standardized units) would allow a better interpretation of results and would facilitate direct comparison of data across studies. Outcomes should be also harmonized for an accurate and reproducible measurement of adverse effects. Appropriate SRs and quantitative synthesis of the evidence should be performed regularly for a continuous update of the risk factors on health outcomes and to determine, if possible, dose-response curves for risk assessment. PMID- 26896855 TI - The role of pluripotency factors to drive stemness in gastrointestinal cancer. AB - A better molecular understanding of gastrointestinal cancers arising either from the stomach, the pancreas, the intestine, or the liver has led to the identification of a variety of potential new molecular therapeutic targets. However, in most cases surgery remains the only curative option. The intratumoral cellular heterogeneity of cancer stem cells, bulk tumor cells, and stromal cells further limits straightforward targeting approaches. Accumulating evidence reveals an intimate link between embryonic development, stem cells, and cancer formation. In line, a growing number of oncofetal proteins are found to play common roles within these processes. Cancer stem cells share features with true stem cells by having the capacity to self-renew in a de-differentiated state, to generate heterogeneous types of differentiated progeny, and to give rise to the bulk tumor. Further, various studies identified genes in cancer stem cells, which were previously shown to regulate the pluripotency circuitry, particularly the so called "Yamanaka-Factors" (OCT4, KLF4, SOX2, and c-MYC). However, the true stemness potential of cancer stem cells and the role and expression pattern of such pluripotency genes in various tumor cell types remain to be explored. Here, we summarize recent findings and discuss the potential mechanisms involved, and link them to clinical significance with a particular focus on gastrointestinal cancers. PMID- 26896856 TI - A 3D culture system enhances the ability of human bone marrow stromal cells to support the growth of limbal stem/progenitor cells. AB - The standard method of cultivating limbal epithelial progenitor/stem cells (LSCs) on a monolayer of mouse 3T3 feeder cells possesses the risk of cross contamination in clinical applications. Human feeder cells have been used to eliminate this risk; however, efficiency from xenobiotic-free cultures on a monolayer appears to be lower than in the standard method using 3T3 cells. We investigated whether bone marrow stromal cells (BMSCs), also known as bone marrow derived mesenchymal stem cells, could serve as feeder cells for the expansion of LSCs in the 3-dimensional (3D) system. Primary single human LSCs on a monolayer of 3T3s served as the control. Very poor growth was observed when single LSCs were cultured on BMSCs. When LSC clusters were cultured on a BMSC monolayer (CC BM), 3D culture system (3D CC-BM) and fibrin 3D system (fibrin 3D CC-BM), the 3D CC-BM method supported a greater LSC expansion. The 3D CC-BM system produced a 2.5-fold higher cell growth rate than the control (p<0.05). The proportion of K14(+) and p63alpha(bright) cells was comparable to those in the control (p>0.05), whereas the proportion of K12(+) cells was lower (p<0.05). These results indicate that BMSCs can efficiently support the expansion of the LSC population in the 3D culture. PMID- 26896858 TI - Sexually dimorphic proteinuria in Wistar rats: Relevance to clinical models. AB - The study investigated the relationship between physiological proteinuria and the histomorphometry of the renal corpuscles in apparently healthy Wistar rats of both sexes, belonging to the same age group. This was with a view to appraise any possible connection between potential expression of sexual dimorphism and the histomorphometry of some integral parts of the glomerular filtration barrier. Twenty Wistar rats of both sexes between ages 9 and 10 weeks were used for this study. This comprised 10 male and 10 female rats weighing 110-200g which were housed in separate metabolic cages for the collection of urine samples.They were sacrificed 24h and 7 days after 2 weeks of acclimatization, respectively. The rats were fasted for 24h during the collection of urine samples. The results showed 74.75% significantly higher urine total protein (p<0.0001), 187.29% significantly higher mg protein/100g body weight (p<0.0001), 32.34% significantly higher Bowman's capsular thickness (p<0.0001), 30.64% significantly higher glomerular thickness (p=0.0002), 59.47% significantly higher Bowman's capsular space (p=0.003), 5.30% insignificantly lower creatinine clearance (p=0.24) and 28.05% significantly higher level of urine protein to creatinine ratio (p<0.0001) in the male when compared with their female counterpart. In conclusion, Wistar rats express sexually dimorphic proteinuria which is structural in origin. PMID- 26896857 TI - Development of a cell-defined siRNA microarray for analysis of gene function in human bone marrow stromal cells. AB - Small interfering RNA (siRNA) screening approaches have provided useful tools for the validation of genetic functions; however, image-based siRNA screening using multiwell plates requires large numbers of cells and time, which could be the barrier in application for gene mechanisms study using human adult cells. Therefore, we developed the advanced method with the cell-defined siRNA microarray (CDSM), for functional analysis of genes in small scale within slide glass using human bone marrow stromal cells (hBMSCs). We designed cell spot system with biomaterials (sucrose, gelatin, poly-L-lysine and matrigel) to control the attachment of hBMSCs inside spot area on three-dimensional (3D) hydrogel-coated slides. The p65 expression was used as a validation standard which described our previous report. For the optimization of siRNA mixture, first, we detected five kinds of commercialized reagent (Lipofectamine 2000, RNAi Max, Metafectine, Metafectine Pro, TurboFectin 8.0) via validation. Then, according to quantification of p65 expression, we selected 2 MUl of RNAi-Max as the most effective reagent condition on our system. Using same validation standard, we optimized sucrose and gelatin concentration (80 mM and 0.13%), respectively. Next, we performed titration of siRNA quantity (2.66-5.55 MUM) by reverse transfection time (24 h, 48 h, 72 h) and confirmed 3.75 MUM siRNA concentration and 48 h as the best condition. To sum up the process for optimized CDSM, 3 MUl of 20 MUM siRNA (3.75 MUM) was transferred to the 384-well V-bottom plate containing 2 MUl of dH2O and 2 MUl of 0.6M sucrose (80 mM). Then, 2 MUl of RNAi-Max was added and incubated for 20 min at room temperature after mixing gently and centrifugation shortly. Five microliters of gelatin (0.26%) and 2 MUl of growth factor reduced phenol red-free matrigel (12.5%) were added and mixed by pipetting gently. Finally, optimized siRNA mixture was printed on 3D hydrogel coated slides and cell-defined attachment and siRNA reverse transfection were induced. The efficiency of this CDSM was verified using three siRNAs (targeting p65, Slug, and N-cadherin), with persistent gene silencing for 5 days. We obtained the significant and reliable data with effective knock-down in our condition, and suggested our method as the qualitatively improved siRNA microarray screening method for hBMSCs. PMID- 26896860 TI - Enhancement of 5-keto-d-gluconate production by a recombinant Gluconobacter oxydans using a dissolved oxygen control strategy. AB - The rapid and incomplete oxidation of sugars, alcohols, and polyols by the gram negative bacterium Gluconobacter oxydans facilitates a wide variety of biological applications. For the conversion of glucose to 5-keto-d-gluconate (5-KGA), a promising precursor of the industrial substance L-(+)-tartaric acid, G. oxydans DSM2343 was genetically engineered to strain ZJU2, in which the GOX1231 and GOX1081 genes were knocked out in a markerless fashion. Then, a secondary alcohol dehydrogenase (GCD) from Xanthomonas campestris DSM3586 was heterologously expressed in G. oxydans ZJU2. The 5-KGA production and cell yield were increased by 10% and 24.5%, respectively. The specific activity of GCD towards gluconate was 1.75+/-0.02 U/mg protein, which was 7-fold higher than that of the sldAB in G. oxydans. Based on the analysis of kinetic parameters including specific cell growth rate (MU), specific glucose consumption rate (qs) and specific 5-KGA production rate (qp), a dissolved oxygen (DO) control strategy was proposed. Finally, batch fermentation was carried out in a 15-L bioreactor using an initial agitation speed of 600 rpm to obtain a high MU for cell growth. Subsequently, DO was continuously maintained above 20% to achieve a high qp to ensure a high accumulation of 5-KGA. Under these conditions, the maximum concentration of 5-KGA reached 117.75 g/L with a productivity of 2.10 g/(L.h). PMID- 26896859 TI - Long-range orbitofrontal and amygdala axons show divergent patterns of maturation in the frontal cortex across adolescence. AB - The adolescent transition from juvenile to adult is marked by anatomical and functional remodeling of brain networks. Currently, the cellular and synaptic level changes underlying the adolescent transition are only coarsely understood. Here, we use two-photon imaging to make time-lapse observations of long-range axons that innervate the frontal cortex in the living brain. We labeled cells in the orbitofrontal cortex (OFC) and basolateral amygdala (BLA) and imaged their axonal afferents to the dorsomedial prefrontal cortex (dmPFC). We also imaged the apical dendrites of dmPFC pyramidal neurons. Images were taken daily in separate cohorts of juvenile (P24-P28) and young adult mice (P64-P68), ages where we have previously discovered differences in dmPFC dependent decision-making. Dendritic spines were pruned across this peri-adolescent period, while BLA and OFC afferents followed alternate developmental trajectories. OFC boutons showed no decrease in density, but did show a decrease in daily bouton gain and loss with age. BLA axons showed an increase in both bouton density and daily bouton gain at the later age, suggesting a delayed window of enhanced plasticity. Our findings reveal projection specific maturation of synaptic structures within a single frontal region and suggest that stabilization is a more general characteristic of maturation than pruning. PMID- 26896861 TI - Production, characterization, gene cloning, and nematocidal activity of the extracellular protease from Stenotrophomonas maltophilia N4. AB - A rhizosphere strain of the bacterium Stenotrophomonas maltophilia N4 secretes the serine protease PN4, whose molecular mass is approximately 42 kDa. The optimal temperature for the enzyme activity of the 11-fold purified protein was 50 degrees C and the optimal pH was 10.5. The activity of the enzyme was strongly inhibited by specific serine protease inhibitors, which allowed for its classification as an alkaline serine protease family. Ca(2+) ions stimulated the activity of the protease PN4, while Mg(2+) ions stabilized its activity, and Zn(2+) and Cd(2+) ions strongly inhibited its activity. The enzyme has broad substrate specificity. For example, it is able to hydrolyse casein, keratin, albumin, haemoglobin, and gelatin, as well as the insoluble modified substrates azure keratin and azocoll. The gene that encodes the 1740 bp precursor form of the enzyme (accession number: LC031815) was cloned. We then deduced that its amino acid sequence includes the region of the conserved domain of the S8 family of peptidases as well as the catalytic triad Asp/His/Ser. The bacterial culture fluid as well as the purified protease PN4 demonstrated biocidal activity with regard to the nematodes Caenorhabditis elegans and Panagrellus spp. PMID- 26896862 TI - Maximum-biomass prediction of homofermentative Lactobacillus. AB - Fed-batch and pH-controlled cultures have been widely used for industrial production of probiotics. The aim of this study was to systematically investigate the relationship between the maximum biomass of different homofermentative Lactobacillus and lactate accumulation, and to develop a prediction equation for the maximum biomass concentration in such cultures. The accumulation of the end products and the depletion of nutrients by various strains were evaluated. In addition, the minimum inhibitory concentrations (MICs) of acid anions for various strains at pH 7.0 were examined. The lactate concentration at the point of complete inhibition was not significantly different from the MIC of lactate for all of the strains, although the inhibition mechanism of lactate and acetate on Lactobacillus rhamnosus was different from the other strains which were inhibited by the osmotic pressure caused by acid anions at pH 7.0. When the lactate concentration accumulated to the MIC, the strains stopped growing. The maximum biomass was closely related to the biomass yield per unit of lactate produced (YX/P) and the MIC (C) of lactate for different homofermentative Lactobacillus. Based on the experimental data obtained using different homofermentative Lactobacillus, a prediction equation was established as follows: Xmax - X0 = (0.59 +/- 0.02).YX/P.C. PMID- 26896863 TI - Thermophile-fermented compost extract as a possible feed additive to enhance fecundity in the laying hen and pig: Modulation of gut metabolism. AB - Recently, we reported that the oral administration of an extract of compost fermented with marine animal resources and thermophilic Bacillus species should confer health benefits in fish, pigs and rodents. Herein, the relations between fecundity and gut metabolites in laying hens and pigs on farms after oral exposure to compost were investigated. On the hen farms, the egg production of hens continuously administered the extract was maintained at significantly higher levels compared with the hens not administered the extract. On the swine farms, after the compost treatment, the shipping dates of fattening pigs were shortened, with an improvement in the death rate of the pigs. When the levels of fecal organic acids, such as short-chain fatty acids, lactate, and ammonium, as indicators of gut metabolism and energy sources for peripheral tissues, were examined, the levels of the acetate, propionate, and butyrate in the feces of the hens and pigs in the compost-treated group were not always different from those in the untreated control group. However, the levels of lactate were consistently low in the feces of both animals after the compost treatment. The fecal ammonium concentrations in old hens (age 597-672 days) and 2-month-old piglets from the compost-fed mother sows were low when compared with the untreated groups. The concentrations of free organic acids and their related compounds in the animal products (eggs and pig loins) were nearly equal to those in the untreated control products. Thus, the oral administration of the thermophile-fermented compost should improve the fecundity of hens and pigs by modifying their gut metabolism. PMID- 26896864 TI - Conversion pattern and predictive factor of mild cognitive impairment in elderly Koreans. AB - OBJECTIVE: We aimed to understand conversion characteristics of mild cognitive impairment (MCI) in elderly Koreans. METHODS: We analyzed clinical data of 760 individuals who participated in a two-year follow-up study. Neuropsychological assessments and clinical examination were conducted in the follow-ups. Logistic regression model was used to estimate predictive risk factors of MCI conversion. RESULT: The participants at baseline (n=760) represented 462 cognitively normal individuals (60.8%), 286 individuals with MCI (37.6%), and 12 individuals with dementia (1.6%). Among the cognitively normal individuals (n=462), 108 (23.4%) progressed to MCI during the two-year follow-up period, including 92 with amnestic mild cognitive impairment (aMCI; 19.9%) and 16 with non-amnestic mild cognitive impairment (non-aMCI; 3.5%). Interestingly, 3.7% of participants with aMCI converted to non-aMCI, while 45.5% of participants with non-aMCI converted to aMCI. Moreover, a higher proportion of non-aMCI (27.3%) reverted to a cognitively normal state, compared to aMCI participants (18.6%), indicating that non-amnestic cognitive impairment is more unstable than amnestic cognitive impairment, and probably converges toward aMCI. Additionally, we found that weight loss was associated with incident MCI and future MCI. Weight loss was negatively correlated with Clinical Dementia Rating (p=0.005), and significantly associated with a higher risk of MCI conversion from a cognitively normal state (OR=1.10, 95% CI: 1.00-1.21, p=0.042). CONCLUSION: This study supports that non amnestic MCI is prone to converge toward amnestic MCI, and the elderly people with weight loss are at risk for developing cognitive decline. PMID- 26896865 TI - Self-weighing in weight management interventions: A systematic review of literature. AB - BACKGROUND: Self-weighing increases a person's self-awareness of current weight and weight patterns. Increased self-weighing frequency can help an individual prevent weight gain. Literature, however, is limited in describing variability in self-weighing strategies and how the variability is associated with weight management outcomes. AIM: This review analyzed self-weighing in weight management interventions and the effects of self-weighing on weight and other outcomes. METHODS: Twenty-two articles from PubMed, CINAHL, Medline, PsychInfo, and Academic Search Premier were extracted for review. RESULTS: These 22 articles reported findings from 19 intervention trials, mostly on weight loss or weight gain prevention. The majority of the reviewed articles reported interventions that combined self-weighing with other self-monitoring strategies (64%), adopted daily self-weighing frequency (84%), and implemented interventions up to six months (59%). One-half of the articles mentioned that technology-enhanced or regular weight scales were given to study participants. Of the articles that provided efficacy data, 75% of self-weighing-only interventions and 67% of combined interventions demonstrated improved weight outcomes. No negative psychological effects were found. CONCLUSIONS: Self-weighing is likely to improve weight outcomes, particularly when performed daily or weekly, without causing untoward adverse effects. Weight management interventions could consider including this strategy. PMID- 26896866 TI - Artifacts in time-resolved NUS: A case study of NOE build-up curves from 2D NOESY. AB - Multidimensional NMR spectroscopy requires time-consuming sampling of indirect dimensions and so is usually used to study stable samples. However, dynamically changing compounds or their mixtures commonly occur in problems of natural science. Monitoring them requires the use multidimensional NMR in a time-resolved manner - in other words, a series of quick spectra must be acquired at different points in time. Among the many solutions that have been proposed to achieve this goal, time-resolved non-uniform sampling (TR-NUS) is one of the simplest. In a TR NUS experiment, the signal is sampled using a shuffled random schedule and then divided into overlapping subsets. These subsets are then processed using one of the NUS reconstruction methods, for example compressed sensing (CS). The resulting stack of spectra forms a temporal "pseudo-dimension" that shows the changes caused by the process occurring in the sample. CS enables the use of small subsets of data, which minimizes the averaging of the effects studied. Yet, even within these limited timeframes, the sample undergoes certain changes. In this paper we discuss the effect of varying signal amplitude in a TR-NUS experiment. Our theoretical calculations show that the variations within the subsets lead to t1-noise, which is dependent on the rate of change of the signal amplitude. We verify these predictions experimentally. As a model case we choose a novel 2D TR-NOESY experiment in which mixing time is varied in parallel with shuffled NUS in the indirect dimension. The experiment, performed on a sample of strychnine, provides a near-continuous NOE build-up curve, whose shape closely reflects the t1-noise level. 2D TR-NOESY reduces the measurement time compared to the conventional approach and makes it possible to verify the theoretical predictions about signal variations during TR-NUS. PMID- 26896867 TI - Ultra broadband NMR spectroscopy using multiple rotating frame technique. AB - The paper describes the design of broadband excitation and inversion pulses by method of multiple rotating frame technique. The ideal situation for perfect excitation and inversion is to have no chemical shift offset and thereby everything on resonance. However, when chemical shifts span a wide range, this condition is not realized. We achieve this condition using a multiply modulated rf-field, whose effect can be understood by progressing into multiple frames. As we progress through the frames, the ratio of chemical shift dispersion to strength of static rf-field decreases, resulting in a final frame, where there is negligible chemical shift as compared to the effective rf-field and we get good excitation and inversion. Increasing the number of frames, increases excitation bandwidth and the ratio of bandwidth to rms excitation amplitude. We show, in principle, it is possible to excite arbitrary large bandwidth for a given rms rf amplitude by increasing the number of frames. The time of excitation increases linearly with the bandwidth when we keep the rms rf-amplitude constant. Experimental demonstration of proposed method is presented on (1)H excitation over a bandwidth of 52 kHz with a rms amplitude of 10 kHz. Increasing the frames increases excitation bandwidth for same rms amplitude of 10 kHz. Experimental spectra obtained from 100%(13)C labeled arginine shows uniform excitation over the entire carbon spectra, obtained with a 8-frame pulse sequence. PMID- 26896868 TI - Development of an outdoor MRI system for measuring flow in a living tree. AB - An outdoor MRI system for noninvasive, long-term measurements of sap flow in a living tree in its natural environment has been developed. An open-access, 0.2 T permanent magnet with a 160 mm gap was combined with a radiofrequency probe, planar gradient coils, electromagnetic shielding, several electrical units, and a waterproofing box. Two-dimensional cross-sectional images were acquired for a ring-porous tree, and the anatomical structures, including xylem and phloem, were identified. The MRI flow measurements demonstrated the diurnal changes in flow velocity in the stem on a per-pixel basis. These results demonstrate that our outdoor MRI system is a powerful tool for studies of water transport in outdoor trees. PMID- 26896869 TI - Design and comparison of exchange spectroscopy approaches to cryptophane-xenon host-guest kinetics. AB - Exchange spectroscopy is used in combination with a variation of xenon concentration to disentangle the kinetics of the reversible binding of xenon to cryptophane-A. The signal intensity of either free or crytophane-bound xenon decays in a manner characteristic of the underlying exchange reactions when the spins in the other pool are perturbed. Three experimental approaches, including the well-known Hyper-CEST method, are shown to effectively entail a simple linear dependence of the signal depletion rate, or of a related quantity, on free xenon concentration. This occurs when using spin pool saturation or inversion followed by free exchange. The identification and quantification of contributions to the binding kinetics is then straightforward: in the depletion rate plot, the intercept at the vanishing free xenon concentration represents the kinetic rate coefficient for xenon detachment from the host by dissociative processes while the slope is indicative of the kinetic rate coefficient for degenerate exchange reactions. Comparing quantified kinetic rates for hyperpolarized xenon in aqueous solution reveals the high accuracy of each approach but also shows differences in the precision of the numerical results and in the requirements for prior knowledge. Because of their broad range of applicability the proposed exchange spectroscopy experiments can be readily used to unravel the kinetics of complex formation of xenon with host molecules in the various situations appearing in practice. PMID- 26896870 TI - An inversion method of 2D NMR relaxation spectra in low fields based on LSQR and L-curve. AB - The low-field nuclear magnetic resonance (NMR) inversion method based on traditional least-squares QR decomposition (LSQR) always produces some oscillating spectra. Moreover, the solution obtained by traditional LSQR algorithm often cannot reflect the true distribution of all the components. Hence, a good solution requires some manual intervention, for especially low signal-to-noise ratio (SNR) data. An approach based on the LSQR algorithm and L curve is presented to solve this problem. The L-curve method is applied to obtain an improved initial optimal solution by balancing the residual and the complexity of the solutions instead of manually adjusting the smoothing parameters. First, the traditional LSQR algorithm is used on 2D NMR T1-T2 data to obtain its resultant spectra and corresponding residuals, whose norms are utilized to plot the L-curve. Second, the corner of the L-curve as the initial optimal solution for the non-negative constraint is located. Finally, a 2D map is corrected and calculated iteratively based on the initial optimal solution. The proposed approach is tested on both simulated and measured data. The results show that this algorithm is robust, accurate and promising for the NMR analysis. PMID- 26896871 TI - Myopia among school students in rural China (Yunnan). AB - PURPOSE: We described the prevalence and associated factors of myopia and high myopia in school children of different ethnicities in a rural community in Yunnan province, China. METHODS: A total of 7681 (93.4%) primary and secondary school students aged 5-16 years in Mangshi participated in this study. Cycloplegic refraction was performed using an auto-refractor. Information regarding demographic factors, socioeconomic status and lifestyle-related exposures were collected using a questionnaire. Multivariate logistic regression models were fitted to estimate the risk factors for myopia and high myopia. RESULTS: The overall prevalence of myopia and high myopia was 39.1% (95% confidence interval [CI]: 38.0, 40.2) and 0.6% (95% CI: 0.4, 0.8) in this study. Myopia prevalence increased significantly with increasing age (p for trend <0.001). Girls were more likely to have myopia compared with boys (p < 0.001). In multivariate analysis, the presence of myopia was associated with increasing height (odds ratio [OR] = 1.02; 95% CI: 1.01, 1.03), computer use (OR = 1.17; 95% CI: 1.03, 1.32), having myopic father (OR = 1.56; 95% CI: 1.24, 1.94), having myopic mother (OR = 1.33; 95% CI: 1.08, 1.63), and increasing time on reading (OR = 1.18; 95% CI: 1.09, 1.28) after adjusting for age, sex and ethnicity. CONCLUSIONS: Nowadays myopia but not high myopia is prevalent among school children in rural China. Significant ethnic differences in myopia prevalence were not observed. A significant 'cohort effect' of myopia previously observed in urban cities had occurred in rural communities in China. PMID- 26896872 TI - Enhancing the ecological validity of the Beads Task as a behavioral measure of intolerance of uncertainty. AB - To broaden the measurement of intolerance of uncertainty (IU) beyond self-report methods, recent research has examined the Beads Task as a behavioral measure of IU. In the present study, we enhanced this task to increase its ecological validity by maximizing decisional uncertainty and the importance of a correct response. Undergraduate participants (n=102) completed the Beads Task with instructions that they would complete the Cold Pressor Task (CPT) if they answered incorrectly. As hypothesized, baseline CPT endurance time and self reported pain level were weakly associated with later Beads Task distress during the decision-making process. Furthermore, in vivo Beads Task distress was associated with self-report inhibitory IU, which measures avoidance and paralysis in the face of uncertainty, but not with prospective IU, perfectionism, or general psychological distress after making statistical adjustments for multiple comparisons. Comparisons to previous work using the Beads Task, clinical implications, and avenues for future research are discussed. PMID- 26896873 TI - A qualitative study of infectious diseases fellowships in Japan. AB - OBJECTIVE: The purpose of this research is to elucidate the actual status of Infectious Diseases (ID) Fellowship programs in Japan to improve them further. METHODS: We conducted qualitative interviews with infectious diseases fellows and his/her faculty consultants from 10 institutions providing ID Fellowships in Japan. We qualitatively analysed the data to delineate the actual status of each program and the fellowship program policies overall, and to identify measures for further improvement. RESULTS: The interviews revealed that there are largely two kinds of ID fellowships; ID programs entirely devoting full time to infectious diseases, and programs that are subordinate concepts of other subspecialties, where only a portion of hours were devoted to ID. Some institutions did not even have an ID department. Time spent by the faculty consultants on fellows also varied among programs. The desire for improvement also varied among interviewees; some being happy with the current system while others demanded radical reform. CONCLUSIONS: Even though there are many ID fellowship programs in Japan, the content, quality, and concepts apparently vary among programs. The perceptions by interviewees on the educational system differed, depending on the standpoints they have on ID physicians. There probably needs to be a coherency in the provision of ID fellowship programs so that fellows acquire competency in the subspecialty with sufficient expertise to act as independent ID specialists. Further studies are necessary for the improvement of ID subspecialty training in Japan. PMID- 26896874 TI - Formalin fixed paraffin embedded (FFPE) material is amenable to HPV detection by the Xpert((r)) HPV assay. AB - BACKGROUND: The Xpert((r)) HPV Assay (Cepheid((r)), Sunnyvale, USA) is a rapid, cartridge-based HPV test validated for use on cervical cytology samples. However, there is an increasing demand for HPV annotation of formalin fixed paraffin embedded (FFPE) material. OBJECTIVES: The aim of this study was to determine the suitability of the Xpert HPV assay for the detection of nucleic acid (NA) derived from FFPE samples. STUDY DESIGN: A total of 88, 10 MUm sections derived from FFPE tissue blocks were assessed, 74 originated from oropharyngeal squamous cell carcinomas (OPSCC) and 14 from a range of other sites. All had previously been tested with a sensitive Luminex((r)) based assay with a component also tested with p16 immunohistochemistry (IHC). NA was extracted from samples using the easyMag((r)) platform and after dilution was added directly to the Xpert cartridge. Agreement between assays was assessed. RESULTS: Overall agreement between the assays was 92%; with a Kappa for HR-HPV detection of 0.833 (95% CI 0.725-0.953). In the 50 samples that had been annotated for p16 status overall agreement between the Xpert assay and the p16 IHC was 90%. CONCLUSIONS: These data indicate that FFPE material is amenable to HPV detection by the Xpert assay. To our knowledge, this is the first study to interrogate the use of the Xpert((r)) HPV assay for this application. PMID- 26896875 TI - Prevalence of positive HIV, HBV, HCV and treponemal tests in blood donors in a rural hospital in southern Ethiopia. PMID- 26896876 TI - Intimate partner violence and HIV-positive women's non-adherence to antiretroviral medication for the purpose of prevention of mother-to-child transmission in Lusaka, Zambia. AB - BACKGROUND: Prevention of mother-to-child transmission (PMTCT) depends critically on HIV-positive women's adherence to antiretroviral drugs during and after pregnancy. Adherence among pregnant and breastfeeding women remains a challenge across sub-Saharan Africa. Power dynamics within couples, such as intimate partner violence, has largely been neglected in research regarding PMTCT adherence. OBJECTIVE: This study aims to determine if there is a relationship between intimate partner violence and non-adherence to PMTCT. METHODS: In 2014, using a verbally administered cross-sectional survey at a large public health clinic in Lusaka, Zambia, 320 HIV-positive postpartum women, who were currently married or living with a man, provided information on their drug adherence during and after pregnancy, as well as relationship dynamics. Adherence was defined as the woman reporting she took or gave to the infant at least 80% of prescribed medication doses. RESULTS: Experiencing intimate partner violence was associated with decreased odds of adherence to PMTCT during and after pregnancy. Different forms of violence affected PMTCT adherence differentially. Physical violence had a less pronounced effect on non-adherence than emotional and sexual violence. A dose-response relationship between intimate partner violence and non-adherence was also observed. CONCLUSIONS: Intimate partner violence is associated with non adherence to PMTCT during and after pregnancy, which deserves increased attention in the effort to eliminate mother-to-child transmission of HIV. PMID- 26896877 TI - Residential patterns in older homeless adults: Results of a cluster analysis. AB - Adults aged 50 and older make up half of individuals experiencing homelessness and have high rates of morbidity and mortality. They may have different life trajectories and reside in different environments than do younger homeless adults. Although the environmental risks associated with homelessness are substantial, the environments in which older homeless individuals live have not been well characterized. We classified living environments and identified associated factors in a sample of older homeless adults. From July 2013 to June 2014, we recruited a community-based sample of 350 homeless men and women aged fifty and older in Oakland, California. We administered structured interviews including assessments of health, history of homelessness, social support, and life course. Participants used a recall procedure to describe where they stayed in the prior six months. We performed cluster analysis to classify residential venues and used multinomial logistic regression to identify individual factors prior to the onset of homelessness as well as the duration of unstable housing associated with living in them. We generated four residential groups describing those who were unsheltered (n = 162), cohabited unstably with friends and family (n = 57), resided in multiple institutional settings (shelters, jails, transitional housing) (n = 88), or lived primarily in rental housing (recently homeless) (n = 43). Compared to those who were unsheltered, having social support when last stably housed was significantly associated with cohabiting and institution use. Cohabiters and renters were significantly more likely to be women and have experienced a shorter duration of homelessness. Cohabiters were significantly more likely than unsheltered participants to have experienced abuse prior to losing stable housing. Pre-homeless social support appears to protect against street homelessness while low levels of social support may increase the risk for becoming homeless immediately after losing rental housing. Our findings may enable targeted interventions for those with different manifestations of homelessness. PMID- 26896879 TI - Causal competition based on generic priors. AB - Although we live in a complex and multi-causal world, learners often lack sufficient data and/or cognitive resources to acquire a fully veridical causal model. The general goal of making precise predictions with energy-efficient representations suggests a generic prior favoring causal models that include a relatively small number of strong causes. Such "sparse and strong" priors make it possible to quickly identify the most potent individual causes, relegating weaker causes to secondary status or eliminating them from consideration altogether. Sparse-and-strong priors predict that competition will be observed between candidate causes of the same polarity (i.e., generative or else preventive) even if they occur independently. For instance, the strength of a moderately strong cause should be underestimated when an uncorrelated strong cause also occurs in the general learning environment, relative to when a weaker cause also occurs. We report three experiments investigating whether independently-occurring causes (either generative or preventive) compete when people make judgments of causal strength. Cue competition was indeed observed for both generative and preventive causes. The data were used to assess alternative computational models of human learning in complex multi-causal situations. PMID- 26896880 TI - Allergy and immunology inpatient and emergency department consultations at a pediatric academic medical center. PMID- 26896881 TI - Vascular ring "mimickring" asthma in a preschool girl with combined immunodeficiency: the benefits of lung function measurements at diagnosis and postoperative follow-up. PMID- 26896878 TI - Socioeconomic status discrimination is associated with poor sleep in African Americans, but not Whites. AB - RATIONALE: Research on self-reported experiences of discrimination and health has grown in recent decades, but has largely focused on racial discrimination or overall mistreatment. Less is known about reports of discrimination on the basis of socioeconomic status (SES), despite the fact that SES is one of the most powerful social determinants of health. OBJECTIVE: We sought to examine the cross sectional association between self-reported SES discrimination and subjective sleep quality, an emerging risk factor for disease. We further examined whether associations differed by race or SES. METHODS: We used logistic and linear regression to analyze data from a population-based cohort of 425 African-American and White middle-aged adults (67.5% female) in the Southeastern United States. SES discrimination was assessed with a modified Experiences of Discrimination Scale and poor subjective sleep quality was assessed with the Pittsburgh Sleep Quality Index. RESULTS: In logistic regression models adjusted for age, gender, and education, reports of SES discrimination were associated with poor sleep quality among African-Americans (OR = 2.39 95%, CI = 1.35, 4.24), but not Whites (OR = 1.03, 95% CI = 0.57, 1.87), and the race * SES discrimination interaction was significant at p = 0.04. After additional adjustments for reports of racial and gender discrimination, other psychosocial stressors, body mass index and depressive symptoms, SES discrimination remained a significant predictor of poor sleep among African-Americans, but not Whites. In contrast to findings by race, SES discrimination and sleep associations did not significantly differ by SES. CONCLUSION: Findings suggest that reports of SES discrimination may be an important risk factor for subjective sleep quality among African-Americans and support the need to consider the health impact of SES-related stressors in the context of race. PMID- 26896882 TI - Growth velocity in prepubertal children using both inhaled and intranasal corticosteroids. PMID- 26896883 TI - Smokeless tobacco use and fractional exhaled nitric oxide in men in a national survey. AB - BACKGROUND: Tobacco use is an important risk for asthma and increases asthma severity. Fractional exhaled nitric oxide (FeNO) is used as a noninvasive biomarker of eosinophilic airway inflammation. Substantial numbers of men use smokeless tobacco. The effect of use of smokeless tobacco on FeNO is not known. OBJECTIVE: To estimate the association between use of smokeless tobacco and FeNO among US men. METHODS: The National Health and Nutrition Examination Survey 2007 2012 was analyzed to assess association of use of smokeless tobacco and FeNO levels in parts per billion in US men. Participants were categorized by smoking status and use of snuff or chewing tobacco in the previous 5 days. FeNO was measured using a device that relies on an electrochemical sensor. RESULTS: In 3,791 male nonsmokers without asthma, weighted mean natural logarithm FeNO by exposure to smokeless tobacco was 2.81 (geometric mean FeNO, 16.59 ppb; 95% CI, 2.77-2.85) in unexposed and 2.66 (geometric mean, 14.30 ppb; 95% CI, 2.55-2.77) in the exposed. In weighted linear regression analyses, use of smokeless tobacco was associated with significantly lower natural logarithm FeNO after controlling for age and race (black vs nonblack) (coefficient, -0.124; SE, 0.056; P = .03; 95% CI, -0.237 to -0.011). Results were unchanged after additionally controlling for recent nitric oxide-rich vegetable consumption and upper respiratory tract infection (coefficient, -0.118; SE, 0.055; P = .04; 95% CI, -0.228 to -0.007). CONCLUSIONS: Use of smokeless tobacco was associated with lower mean natural logarithm FeNO levels in nonsmokers with no history of asthma. Interpretation of FeNO should consider all forms of tobacco use. PMID- 26896885 TI - Response of the water-water cycle to the change in photorespiration in tobacco. AB - Photosynthetic electron transport produces ATP and NADPH, which are used by the primary metabolism. The production and consumption of ATP and NADPH must be balanced to maintain steady-state rates of CO2 assimilation and photorespiration. It has been indicated that the water-water cycle (WWC) is indispensable for driving photosynthesis via increasing ATP/NADPH production. However, the relationship between the WWC and photorespiration is little known. We tested the hypothesis that the WWC responds to change in photorespiration by balancing ATP/NADPH ratio. Measurements of gas exchange and chlorophyll fluorescence were conducted in tobacco plants supplied with high (HN-plants) or low nitrogen concentration (LN-plants). The WWC was activated under high light but not low light in both HN-plants and LN-plants. HN-plants had significantly higher capacities of the WWC and photorespiration than LN-plants. Under high light, the relative high WWC activation in HN-plants was accompanied with relative low levels of NPQ compared LN-plants, suggesting that the main role of the WWC under high light was to favor ATP synthesis but not to activate NPQ. Interestingly, the activation of WWC was positively correlated to the electron flow devoted to RuBP oxygenation, indicating that the WWC plays an important role in energy balancing when photorespiration is high. We conclude that the WWC is an important flexible mechanism to optimize the stoichiometry of the ATP/NADPH ratio responding to change in photorespiration. Furthermore, HN-plants enhance the WWC activity to maintain higher rates of CO2 assimilation and photorespiration. PMID- 26896884 TI - Multiple opportunistic fungal infections in an individual with severe HIV disease: A case report. AB - BACKGROUND: Fungal infections have been commonly diagnosed in individuals with advanced HIV disease. Cryptococcosis, pneumocystosis, and histoplasmosis are the most frequent systemic mycoses in people suffering from HIV/AIDS. CASE REPORT: We report a case of multiple fungal infections in an advanced AIDS-patient. A 33 year-old HIV-positive man from Brazil was hospitalized due to diarrhea, dyspnea, emaciation, hypoxemia, extensive oral thrush, and a CD4+ T lymphocyte count of 20cells/mm(3). Honeycombed-structures consistent with Pneumocystis jirovecii were observed by direct immunofluorescence in induced sputum. Cryptococcus neoformans was recovered from respiratory secretion and cerebrospinal fluid cultures. Histopathology of the bone marrow also revealed the presence of Histoplasma capsulatum. Molecular assays were performed in a sputum sample. Nested-PCR confirmed the presence of P. jirovecii and H. capsulatum; qPCR multiplex was positive for C. neoformans and H. capsulatum. With the treatment of antifungal drugs the patient progressed satisfactorily. CONCLUSIONS: The diagnosis of several systemic mycoses demonstrates the vulnerability of advanced AIDS patients. Thus, the detection of AIDS cases in the early stages of infection is necessary for a prompt and adequate introduction of HAART therapy, and the use of prophylaxis to control opportunistic infections. PMID- 26896886 TI - GuideLiner-Facilitated Rotational Atherectomy in Calcified Right Coronary Artery: The "Child" Makes the Difference. PMID- 26896887 TI - A Unique Case of May-Thurner Syndrome: Extrinsic Compression of the Common Iliac Vein After Iliac Artery Stenting. PMID- 26896888 TI - Impact of Right Atrial Pressure on Fractional Flow Reserve Measurements: Comparison of Fractional Flow Reserve and Myocardial Fractional Flow Reserve in 1,600 Coronary Stenoses. AB - OBJECTIVES: This study sought to assess the impact of a wide range of mean right atrial pressure (Pra) on fractional flow reserve (FFR) measurements. BACKGROUND: FFR invasively assesses the ischemic potential of coronary stenoses. FFR is calculated as the ratio of mean distal coronary pressure (Pd) to mean aortic pressure (Pa) during maximal hyperemia. The Pra is considered to have little impact if it is within normal range, so it is neglected in the formula. METHODS: In 1,676 stenoses of 1,235 patients undergoing left-right heart catheterization for ischemic (642 [52%]) or valvular heart disease (593 [48%]), the authors compared the FFR values calculated without accounting for Pra (FFR= Pd/Pa) to the corresponding myocardial fractional flow reserve (FFRmyo) values accounting for Pra (FFRmyo = Pd - Pra/Pa - Pra). RESULTS: The median Pra was 7 (interquartile range [IQR]: 5 to 10) mm Hg with a maximum of 27 mm Hg. The correlation and agreement between FFR and FFRmyo was excellent (R(2) = 0.987; slope 1.096 +/- 0.003). The median FFR (0.85; IQR: 0.78 to 0.91) was slightly but statistically significantly higher than the median FFRmyo (0.83; IQR: 0.76 to 0.90; p < 0.001) with a median difference of 0.01 (IQR: 0.01 to 0.02). Values of FFR above the cutoff of 0.80 provided an FFRmyo <=0.80 in 110 (9%) stenoses. No FFR value above 0.80 provided an FFRmyo <=0.75. CONCLUSIONS: The difference between FFR and FFRmyo was minimal even in patients with markedly increased Pra. FFR values above the gray zone (i.e., >0.80) did not yield values below the gray zone (i.e., <=0.75) in any case, which suggests that the impact of right atrial pressure on FFR measurement is indeed negligible. PMID- 26896889 TI - Multimodality Imaging of Bioprosthetic Percutaneous Balloon Valvuloplasty Followed by Valve-in-Valve Implantation for Mitral Stenosis Due to Commissural Leaflet Fusion. PMID- 26896891 TI - COAST-ing Toward Covered Stents for Aortic Coarctation: Not All Plain Sailing! PMID- 26896890 TI - Immediate Outcomes of Covered Stent Placement for Treatment or Prevention of Aortic Wall Injury Associated With Coarctation of the Aorta (COAST II). AB - OBJECTIVES: This study aimed to describe the safety and short-term efficacy of the Covered Cheatham-Platinum stent (CCPS) in treating or preventing aortic wall injury (AWI) in patients with coarctation of the aorta (CoA). BACKGROUND: The COAST II trial (Covered Cheatham-Platinum Stents for Prevention or Treatment of Aortic Wall Injury Associated with Coarctation of the Aorta Trial) is a multicenter, single-arm trial using the CCPS for the treatment and/or prevention of AWI in patients with CoA and pre-existing AWI or increased risk of AWI. METHODS: Patients were enrolled if they had a history of CoA with pre-existing AWI (Treatment group) or with increased risk of AWI (Prevention group). Pre/post implant hemodynamics and angiography were reported. A core laboratory performed standardized review of all angiograms. One-month follow-up was reported. RESULTS: A total of 158 patients (male = 65%; median age 19 years) underwent placement of CCPS. Eighty-three patients had pre-existing AWI. The average ascending-to descending aorta systolic gradient improved from 27 +/- 20 mm Hg to 4 +/- 6 mm Hg. Complete coverage of pre-existing AWI was achieved in 66 of 71 patients (93%) with AWI who received a single CCPS. Ultimately, complete coverage of AWI was achieved in 76 of 83 patients (92%); 7 patients had minor endoleaks that did not require repeat intervention. Four patients experienced important access site vascular injury. There were no acute AWI, repeat interventions, or deaths. CONCLUSIONS: The CCPS can effectively treat and potentially prevent AWI associated with CoA. Access site arterial injury is the most common important complication. Longer-term follow-up is necessary to define mid- and late-term outcomes. PMID- 26896892 TI - Validating Practicality: Impact of Right Atrial Pressure on Fractional Flow Reserve. PMID- 26896893 TI - The health effects of ambient PM2.5 and potential mechanisms. AB - The impacts of ambient PM2.5 on public health have become great concerns worldwide, especially in the developing countries. Epidemiological and toxicological studies have shown that PM2.5 does not only induce cardiopulmonary disorders and/or impairments, but also contributes to a variety of other adverse health effects, such as driving the initiation and progression of diabetes mellitus and eliciting adverse birth outcomes. Of note, recent findings have demonstrated that PM2.5 may still pose a hazard to public health even at very low levels (far below national standards) of exposure. The proposed underlying mechanisms whereby PM2.5 causes adverse effects to public health include inducing intracellular oxidative stress, mutagenicity/genotoxicity and inflammatory responses. The present review aims to provide an brief overview of new insights into the molecular mechanisms linking ambient PM2.5 exposure and health effects, which were explored with new technologies in recent years. PMID- 26896894 TI - Octylphenol induced gene expression in testes of Frog, Rana chensinensis. AB - Octylphenol (OP) is an endocrine-disrupting chemical (EDC), which can disrupt the reproductive system. To understand the effect of OP, a subtractive cDNA library was constructed using suppression subtractive hybridization (SSH) to identify alterations of gene transcription in the testes of the frog Rana chensinensis after OP exposure. Two hundred positive clones were selected and 134 sequences of gene fragments were produced from the subtractive library randomly. These genes were identified to be involved in metabolic process, cellular process, biological regulation, stimulus, immune system and female pregnancy process. In order to verify the efficiency of the subtractive cDNA library, PSG9 and PAPP-A were analyzed further as two representatives of differentially expressed transcription genes using semi-quantitative RT-PCR. Our result was the first successful construction of the subtractive cDNA library in frog testes after OP treatment. Based on this cDNA library, OP was shown to affect multiple physiological processes including inducing immune response, disrupting the steroid hormone synthesis and influencing spermatogenesis in the testis by up-regulation of specific genes. PMID- 26896895 TI - Lettuce irrigated with contaminated water: Photosynthetic effects, antioxidative response and bioaccumulation of microcystin congeners. AB - The use of microcystins (MCs) contaminated water to irrigate crop plants represents a human health risk due to their bioaccumulation potential. In addition, MCs cause oxidative stress and negatively influence photosynthetic activities in plants. The present study was aimed at investigating the effect of MCs on photosynthetic parameters and antioxidative response of lettuce. Furthermore, the bioaccumulation factor (BAF) of total MCs, MC-LR and MC-RR in the vegetable after irrigation with contaminated water was determined. Lettuce crops were irrigated for 15 days with water containing cyanobacterial crude extracts (Microcystis aeruginosa) with MC-LR (0.0, 0.5, 2.0, 5.0 and 10.0 ug L( 1)), MC-RR (0.0, 0.15, 0.5, 1.5 and 3.0 ug L(-1)) and total MCs (0.0, 0.65, 2.5, 6.5 and 13.0 ug L(-1)). Increased net photosynthetic rate, stomatal conductance, leaf tissue transpiration and intercellular CO2 concentration were recorded in lettuce exposed to different MCs concentrations. Antioxidant response showed that glutathione S-transferase activity was down-regulated in the presence of MCs. On the other hand, superoxide dismutase, catalase and peroxidase activities were upregulated with increasing MCs concentrations. The bioaccumulation factor (BAF) of total MCs and MC-LR was highest at 6.50 and 5.00 ug L(-1), respectively, while for MC-RR, the highest BAF was recorded at 1.50 ug L(-1) concentration. The amount of total MCs, MC-LR and MC-RR bioacumulated in lettuce was highest at the highest exposure concentrations. However, at the lowest exposure concentration, there were no detectable levels of MC-LR, MC-RR and total MCs in lettuce. Thus, the bioaccumulation of MCs in lettuce varies according to the exposure concentration. In addition, the extent of physiological response of lettuce to the toxins relies on exposure concentrations. PMID- 26896897 TI - Formation of an Exercise in CKD Working Group. PMID- 26896896 TI - Imazapyr+imazapic herbicide determines acute toxicity in silver catfish Rhamdia quelen. AB - Imazapyr (IMY) and imazapic (IMI) are imidazolinone herbicides which have been associated in a commercial formulation (Kifix((r))). To date, there are no studies on the toxicity of an IMY+IMI herbicide in fish. This work aimed to assess the acute toxicity (24 and 96 h) of IMY+IMI (0, 0.488 and 4.88 ug/L) towards Rhamdia quelen through hematological, biochemical, immunological, ionoregulatory and enzymatic indexes. Red blood cell count was lower at 4.88 than at 0.488 ug/L (24 and 96 h); mean corpuscular volume was lower than control at both concentrations (24 h) and at 0.488 ug/L (96 h); lymphocytes declined at 4.88 ug/L comparing to control (96 h); and monocytes increased at 4.88 ug/L (96 h) in comparison with the respective control and with 4.88 ug/L at 24h. Aspartate aminotransferase was higher at 0.488 ug/L (96 h) than the respective control and the respective concentration at 24 h; uric acid reduced at 4.88 ug/L comparing with 0.488 ug/L (96 h); and cortisol was lower at 4.88 ug/L compared to 0.488 ug/L and control (96 h). Herbicide exposure lowered plasma bactericidal activity at both concentrations (24 h) and at 0.488 ug/L (96 h); and plasma complement activity declined at 4.88 ug/L comparing with 0.488 ug/L and control (96 h), and was lower at all concentrations at 96 h than at 24 h. Plasma K(+) levels were higher at 4.88ug/L than in the remaining groups (24 and 96h); and Na(+) levels decreased at 4.88 ug/L compared to control (96 h). Na(+)/K(+)-ATPase and H(+) ATPase activities in gills were lower at 4.88 ug/L comparing with control (24 h) and with the respective concentration at 96 h; and AChE activity in brain was higher at 0.488 and 4.88 ug/L than control (24 h) and the respective concentrations at 96 h, while in muscle it was higher at 0.488 and 4.88 ug/L than control (96 h) and the respective concentrations at 24 h. The present findings demonstrate that, despite IMY+IMI targets the animal-absent AHAS enzyme, such formulation displayed an acute toxic effect upon R. quelen homeostasis by impacting on vital functions such as immune defense, metabolism, ionoregulation and neurotransmission. PMID- 26896898 TI - C4 Glomerulopathy: A Disease Entity Associated With C4d Deposition. AB - Complement-mediated glomerulonephritis, which includes C3 glomerulopathy, is characterized by dominant staining of C3 with minimal or no immunoglobulin deposits on immunofluorescence studies. We describe a new entity of complement mediated glomerulonephritis that is characterized by bright C4d staining but with no or minimal C3 or immunoglobulin deposits on immunofluorescence studies. We label this entity as C4 glomerulopathy. C4 glomerulopathy includes C4 dense deposit disease and C4 glomerulonephritis. C4 dense deposit disease is characterized by bright C4d staining and dense deposits along glomerular basement membranes. C4 glomerulonephritis is characterized by bright C4d staining and many mesangial electron-dense deposits, with or without rare intramembranous electron dense deposits. We describe clinical features and kidney biopsy results in a short series of 3 patients to highlight these findings. All 3 patients presented with proteinuria, and 2 patients also had hematuria. Kidney function was preserved in 2 patients, whereas 1 patient presented with declining kidney function. Evaluation for autoimmune disease, infection, and paraprotein yielded negative results in all patients. Complement levels were normal, although 1 patient had borderline low C4 levels. Kidney biopsy showed mesangial proliferative or membranoproliferative glomerulonephritis with bright C4d staining and absent or minimal C1q, C3, and immunoglobulin. Laser microdissection and mass spectrometry of glomeruli in all 3 patients showed large to moderate numbers of spectra matching C4. Furthermore, analysis of amino acid sequences showed that they were localized to the C4d portion of C4, consistent with immunofluorescence findings. Further studies are required to determine the underlying cause. In summary, we describe a novel complement-mediated glomerulonephritis that is characterized by bright glomerular C4d staining with minimal or absent staining for C1q, C3, and immunoglobulin. PMID- 26896899 TI - 0.9% Saline or Balanced Crystalloid Fluids for Critically Ill Patients: SPLIT Decision? PMID- 26896900 TI - Inhibition drives configural superiority of illusory Gestalt: Combined behavioral and drift-diffusion model evidence. AB - Illusory Kanizsa figures demonstrate that a perceptually completed whole is more than the sum of its composite parts. In the current study, we explored part/whole relationships in object completion using the configural superiority effect (CSE) with illusory figures (Pomerantz & Portillo, 2011). In particular, we investigated to which extent the CSE is modulated by closure in target and distractor configurations. Our results demonstrated a typical CSE, with detection of a configural whole being more efficient than the detection of a corresponding part-level target. Moreover, the CSE was more pronounced when grouped objects were presented in distractors rather than in the target. A follow-up experiment systematically manipulated closure in whole target or, respectively, distractor configurations. The results revealed the effect of closure to be again stronger in distractor, rather than in target configurations, suggesting that closure primarily affects the inhibition of distractors, and to a lesser extent the selection of the target. In addition, a drift-diffusion model analysis of our data revealed that efficient distractor inhibition expedites the rate of evidence accumulation, with closure in distractors particularly speeding the drift toward the decision boundary. In sum, our findings demonstrate that the CSE in Kanizsa figures derives primarily from the inhibition of closed distractor objects, rather than being driven by a conspicuous target configuration. Altogether, these results support a fundamental role of inhibition in driving configural superiority effects in visual search. PMID- 26896901 TI - Pupillary responses reveal infants' discrimination of facial emotions independent of conscious perception. AB - Sensitive responding to others' emotions is essential during social interactions among humans. There is evidence for the existence of subcortically mediated emotion discrimination processes that occur independent of conscious perception in adults. However, only recently work has begun to examine the development of automatic emotion processing systems during infancy. In particular, it is unclear whether emotional expressions impact infants' autonomic nervous system regardless of conscious perception. We examined this question by measuring pupillary responses while subliminally and supraliminally presenting 7-month-old infants with happy and fearful faces. Our results show greater pupil dilation, indexing enhanced autonomic arousal, in response to happy compared to fearful faces regardless of conscious perception. Our findings suggest that, early in ontogeny, emotion discrimination occurs independent of conscious perception and is associated with differential autonomic responses. This provides evidence for the view that automatic emotion processing systems are an early-developing building block of human social functioning. PMID- 26896902 TI - Language supports young children's use of spatial relations to remember locations. AB - Two experiments investigated the role of language in children's spatial recall performance. In particular, we assessed whether selecting an intrinsic reference frame could be improved through verbal encoding. Selecting an intrinsic reference frame requires remembering locations relative to nearby objects independent of one's body (egocentric) or distal environmental (allocentric) cues, and does not reliably occur in children under 5 years of age (Nardini, Burgess, Breckenridge, & Atkinson, 2006). The current studies tested the relation between spatial language and 4-year-olds' selection of an intrinsic reference frame in spatial recall. Experiment 1 showed that providing 4-year-olds with location-descriptive cues during (Exp. 1a) or before (Exp. 1b) the recall task improved performance both overall and specifically on trials relying most on an intrinsic reference frame. Additionally, children's recall performance was predicted by their verbal descriptions of the task space (Exp. 1a control condition). Non-verbally highlighting relations among objects during the recall task (Exp. 2) supported children's performance relative to the control condition, but significantly less than the location-descriptive cues. These results suggest that the ability to verbally represent relations is a potential mechanism that could account for developmental changes in the selection of an intrinsic reference frame during spatial recall. PMID- 26896903 TI - Imagination in human social cognition, autism, and psychotic-affective conditions. AB - Complex human social cognition has evolved in concert with risks for psychiatric disorders. Recently, autism and psychotic-affective conditions (mainly schizophrenia, bipolar disorder, and depression) have been posited as psychological 'opposites' with regard to social-cognitive phenotypes. Imagination, considered as 'forming new ideas, mental images, or concepts', represents a central facet of human social evolution and cognition. Previous studies have documented reduced imagination in autism, and increased imagination in association with psychotic-affective conditions, yet these sets of findings have yet to be considered together, or evaluated in the context of the diametric model. We first review studies of the components, manifestations, and neural correlates of imagination in autism and psychotic-affective conditions. Next, we use data on dimensional autism in healthy populations to test the hypotheses that: (1) imagination represents the facet of autism that best accounts for its strongly male-biased sex ratio, and (2) higher genetic risk of schizophrenia is associated with higher imagination, in accordance with the predictions of the diametric model. The first hypothesis was supported by a systematic review and meta-analysis showing that Imagination exhibits the strongest male bias of all Autism Quotient (AQ) subscales, in non-clinical populations. The second hypothesis was supported, for males, by associations between schizophrenia genetic risk scores, derived from a set of single-nucleotide polymorphisms, and the AQ Imagination subscale. Considered together, these findings indicate that imagination, especially social imagination as embodied in the default mode human brain network, mediates risk and diametric dimensional phenotypes of autism and psychotic-affective conditions. PMID- 26896904 TI - Survivorship and clinical outcomes after multi-level anterior lumbar reconstruction with stand-alone anterior lumbar interbody fusion or hybrid construct. AB - In multilevel disc disease, there is still uncertainty regarding whether multiple total disc replacement is more effective and safer than fusion. Our objective was to measure and compare the clinical outcome of multilevel hybrid constructs with stand-alone anterior lumbar interbody fusion (ALIF) using a retrospective analysis. Sixty-four patients with chronic low back pain determined to be from two or three-level degenerative disc disease were included. Thirty-three patients were treated with hybrid fusion and 31 with ALIF. Several parameters were retrospectively reviewed, including blood loss, operation time, hospital stay, Visual Analog Scale (VAS) score, Oswestry Disability Index (ODI), and survivorship without the need for revision surgery. Telephone follow-ups were conducted to ascertain survivorship, clinical outcomes (VAS, ODI) and patient satisfaction. Operation time was longer in the hybrid group (p=0.021). The hybrid group showed a significant improvement in VAS and ODI with 52.2% and 50.0% improvement versus 28.3% and 25.5% in the ALIF group (p<0.05). At the telephone follow-up for patient satisfaction, 95.7% (n=22) of the hybrid group were satisfied and 95.2% (n=21) of the ALIF group were satisfied. Seventy-four percent (n=17) in the hybrid group and 85.7% (n=18) in the ALIF group would choose to do the initial surgery again. Kaplan-Meier analysis showed 80.5% survivorship for hybrids and 75.9% for ALIF at 5years. With our clinical outcomes in VAS and ODI scores, these results, when taken together, indicate that hybrid fusion is a valid and viable alternative to ALIF fusion, with at least equal if not better clinical outcomes in terms of survivorship, back pain, and disability scores. PMID- 26896905 TI - iPad colour vision apps for dyschromatopsia screening. AB - Optic neuritis (ON) is a common and important cause of vision loss or vision disturbances in the community, particularly amongst the young, and it is often associated with a persistent dyschromatopsia. Traditionally screening for dyschromatopsia has been carried out using pseudo-isochromatic Ishihara plates. These colour plates were originally developed for testing of colour blindness, and indeed have only more recently been applied to ON. As the Ishihara plate books used for testing are expensive, unwieldy, and are not commonly available in many clinics or wards, many neurologists and ophthalmologists have taken to using untested and unstudied downloadable software packages on portable electronic devices for testing. This study compared the efficacy of printed and iPad (Apple, Cupertino, CA, USA) versions of the Ishihara plates in screening for dyschromatopsia in patients who were suspected of having ON. The main finding was that dyschromatopsia testing using a commercially available application on an iPad was comparable to using the current pragmatic clinical benchmark, the pseudo isochromatic plates of Ishihara. These findings provide support for the increasingly common practice of screening for dyschromatopsia using the iPad. PMID- 26896906 TI - Breadth versus volume: Neurology outpatient clinic cases in medical education. AB - This study examined how volume in certain patient case types and breadth across patient case types in the outpatient clinic setting are related to Neurology Clerkship student performance. Case logs from the outpatient clinic experience of 486 students from The University of Chicago Pritzker School of Medicine, USA, participating in the 4week Neurology Clerkship from July 2008 to June 2013 were reviewed. A total of 12,381 patient encounters were logged and then classified into 13 diagnostic categories. How volume of cases within categories and the breadth of cases across categories relate to the National Board of Medical Examiners Clinical Subject Examination for Neurology and a Neurology Clerkship Objective Structured Clinical Examination was analyzed. Volume of cases was significantly correlated with the National Board of Medical Examiners Clinical Subject Examination for Neurology (r=.290, p<.001), the Objective Structured Clinical Examination physical examination (r=.236, p=.011), and the Objective Structured Clinical Examination patient note (r=.238, p=.010). Breadth of cases was significantly correlated with the National Board of Medical Examiners Clinical Subject Examination for Neurology (r=.231, p=.017), however was not significantly correlated with any component of the Objective Structured Clinical Examination. Volume of cases correlated with higher performance on measures of specialty knowledge and clinical skill. Fewer relationships emerged correlating breadth of cases and performance on the same measures. This study provides guidance to educators who must decide how much emphasis to place on volume versus breadth of cases in outpatient clinic learning experiences. PMID- 26896907 TI - Pituitary aspergillus infection. AB - Fungal infection should be considered in the differential diagnosis of a pituitary or sellar mass, albeit fungal infections involving the pituitary gland and sella are a rare occurrence. We report a case of Aspergillus infection involving the pituitary gland and sellar region discovered in a 74-year-old man. The patient had a history of hypertension, chronic renal disease, autoimmune hemolytic anemia and presented with right eye pain, headaches and worsening hemiparesis. Imaging studies revealed a right internal carotid artery occlusion and an acute right pontine stroke along with smaller infarcts in the right middle cerebral artery distribution. Clinically, the patient was thought to have vasculitis. An infectious etiology was not identified. He developed respiratory distress and died. At autopsy, necrotizing meningitis was discovered. A predominantly chronic inflammatory cell infiltrate consisting of benign-appearing lymphocytes, plasma cells and macrophages was accompanied by acute angle branching, angioinvasive hyphae which were highlighted on Gomori methenamine silver staining and were morphologically consistent with Aspergillus species. In previously reported cases of Aspergillus infection involving the pituitary or sella, most presented with headaches or impaired vision and were not immunocompromised. A transsphenoidal surgical approach is recommended in suspected cases in order to minimize the risk of dissemination of the infection. Some patients have responded well to antifungal medications once diagnosed. PMID- 26896908 TI - Isolated asymptomatic pulmonary arteriovenous malformation presenting with ischaemic stroke. AB - Young onset stroke is uncommon, and may be due to conditions other than traditional vascular risk factors. A 42-year-old woman with an ischaemic stroke was found to have left atrial bubble study positivity on transthoracic echocardiogram (TTE) suggestive of patent foramen ovale, however she also had low peripheral oxygen saturation. Investigation revealed an isolated pulmonary arteriovenous malformation (PAVM), visible on admission chest radiograph. This can cause embolic stroke and is an alternate cause of the TTE findings. The PAVM was able to be closed via endovascular intervention, removing the shunt and therefore removing her risk of recurrent stroke events. This is a rare cause of embolic stroke in young people which can be easily missed on investigation yet is amenable to treatment. PMID- 26896909 TI - Asymptomatic diffuse "encephalitic" cerebral toxoplasmosis in a woman with systemic lupus erythematosus. AB - Classic cerebral toxoplasmosis typically presents with neurologic symptoms such as seizures and mental status changes and histological examination shows focal lesions with necrosis. However, in the diffuse "encephalitic" form, patients are asymptomatic with diffuse, inflammatory, non-necrotic lesions. Asymptomatic diffuse "encephalitic" toxoplasmosis has been reported only in four acquired immunodeficiency syndrome patients and one human immunodeficiency virus (HIV) negative patient with chronic lymphocytic leukemia. We present a 36-year-old HIV negative woman with systemic lupus erythematosus and lupus nephritis who was on immunosuppression for 9years after cadaveric renal transplant and died from pulmonary hemorrhage and cytomegalovirus pneumonia. Brain autopsy findings revealed multifocal microglial nodules containing Toxoplasma bradyzoites and associated astrogliosis. These nodules were prominent in the cerebellum, midbrain and medulla and also present in the cortex and thalamus. No coagulative necrosis, necrotizing abscesses, or other opportunistic infections were present. The patient had previously exhibited no neurologic symptoms and there was no clinical suspicion for toxoplasmosis. To the best of our knowledge, this is the first case of diffuse, non-necrotizing, "encephalitic" cerebral toxoplasmosis reported in a lupus patient and also the first reported female case. PMID- 26896910 TI - Persistent anosmia and olfactory bulb atrophy after mulga (Pseudechis australis) snakebite. AB - Loss of sense of smell is an intriguing yet under-recognised complication of snakebite. We report olfactory function testing and neuroimaging of the olfactory bulbs in a 30-year-old man with anosmia persisting for more than 1year after mulga (Pseudechis australis) snakebite. This problem was first noted by the patient 1week after being definitely bitten in Queensland, Australia. He had then presented to a regional hospital where his envenomation was considered mild enough to not warrant antivenom administration. A week later the patient noted a reduction of sense of smell, which progressed to complete inability to smell over the ensuing weeks. On clinical review the patient's neurologic and rhinologic examination did not reveal any structural cause for anosmia. Formal olfactory testing was performed using ''sniffin' sticks" and the patient scored 17 on this test, indicating severe hyposmia (functional anosmia <16.5, normal score >30.3 for men aged 16-35years). MRI of the brain showed no abnormalities. The olfactory bulb volumes were then measured on a volumetric T2-weighted MRI that demonstrated significantly reduced volume of both bulbs, with the right 34.86mm(3) and left 36.25mm(3) (normal volume ?58mm(3), 10th centile). The current patient represents a rare instance of a definite, untreated, elapid (mulga snake) envenomation with an intriguing disjunction between the mildness of the systemic features and the severity of the olfactory lesion. It is also unclear if early antivenom use attenuates this condition, and due to the delayed manifestation of the symptoms, awareness of this phenomenon may be lacking amongst physicians. PMID- 26896911 TI - Intravenous thrombolysis, mechanical embolectomy, and intracranial stenting for hyperacute ischemic stroke in a patient with moyamoya disease. AB - The Japanese translation of moyamoya means "puff of smoke" and refers to the angiographic appearance of dilated collateral vessels seen during chronic progressive narrowing of the intracranial supraclinoid portions of the internal carotid arteries. Despite cerebral ischemia being the most common presenting symptom, 20% to 40% of adults suffer a hemorrhagic stroke. Due to the lack of evidence and histopathologic findings, intravenous and endovascular reperfusion therapy is typically avoided. This case study presents a patient with moyamoya disease in the hyperacute phase of ischemic stroke. The patient received full dose (0.9mg/kg) tissue plasminogen activator and subsequently underwent a mechanical clot extraction and Wingspan stent (Stryker, Kalamazoo, MI, USA) placement. The use of these options in the setting of moyamoya disease is novel. This demonstrates that moyamoya disease may not be an absolute contraindication to revascularization in hyperacute ischemic stroke and underscores that many perceived contraindications to thrombolytic and mechanical revascularization therapies are relative. PMID- 26896912 TI - [Corrected QT interval during therapeutic hypothermia in hypoxic ischaemic encephalopathy]. AB - INTRODUCTION: Therapeutic hypothermia is the standard treatment for hypoxic ischaemic encephalopathy (HIE), despite not knowing all its effects and complications. Sinus bradycardia is one of the consequences of cooling that has been previously documented in the literature, but little is known about the cardiac electrical activity in these patients. OBJECTIVE: To determine the corrected QT (QTc) interval in newborns treated with therapeutic hypothermia for HIE. MATERIAL AND METHODS: A prospective observational study was conducted in all patients treated with hypothermia for HIE that were admitted to our Unit between November 2012 and October 2013. ECGs were performed during hypothermia (every 24h), during the re-warming period (at 34.5 degrees C, 35.5 degrees C, 36.5 degrees C), and on the 7th day of life. RESULTS: A total of 19 patients were included. A prolonged QTc was observed in all patients during hypothermia, and 84% (n=16) had prolonged QTc in all the ECGs during treatment. In 3 patients, one of the ECGs did not have a prolonged QTc. After re-warming, the QTc interval returned to normal in all patients. No statistically significant differences were seen when the degree of HIE (P=.192) or the use of inotropic support (P=.669) were considered. CONCLUSIONS: Therapeutic hypothermia applied to asphyxiated newborns with HIE seems to induce a QTc prolongation that resolves when the patient regains physiological temperature. PMID- 26896913 TI - Music therapy and Alzheimer's disease: Cognitive, psychological, and behavioural effects. AB - INTRODUCTION: Music therapy is one of the types of active ageing programmes which are offered to elderly people. The usefulness of this programme in the field of dementia is beginning to be recognised by the scientific community, since studies have reported physical, cognitive, and psychological benefits. Further studies detailing the changes resulting from the use of music therapy with Alzheimer patients are needed. OBJECTIVES: Determine the clinical improvement profile of Alzheimer patients who have undergone music therapy. PATIENTS AND METHODS: Forty two patients with mild to moderate Alzheimer disease underwent music therapy for 6 weeks. The changes in results on the Mini-mental State Examination, Neuropsychiatric Inventory, Hospital Anxiety and Depression Scale and Barthel Index scores were studied. We also analysed whether or not these changes were influenced by the degree of dementia severity. RESULTS: Significant improvement was observed in memory, orientation, depression and anxiety (HAD scale) in both mild and moderate cases; in anxiety (NPI scale) in mild cases; and in delirium, hallucinations, agitation, irritability, and language disorders in the group with moderate Alzheimer disease. The effect on cognitive measures was appreciable after only 4 music therapy sessions. CONCLUSIONS: In the sample studied, music therapy improved some cognitive, psychological, and behavioural alterations in patients with Alzheimer disease. Combining music therapy with dance therapy to improve motor and functional impairment would be an interesting line of research. PMID- 26896914 TI - Preparation of phenylboronate affinity rigid monolith with macromolecular porogen. AB - Boronate-affinity monolithic column was first prepared via polystyrene (PS) as porogen in this work. The monolithic polymer was synthetized using 4 vinylphenylboronic acid (4-VPBA) as functional monomer, ethylene glycol dimethacrylate (EDMA) as crosslinker monomer, and a mixture of PS solution in tetrahydrofuran, the linear macromolecular porogen, and toluene as porogen. Isoquercitrin (ISO) and hyperoside (HYP), isomer diol flavonoid glycosides, can be baseline separated on the poly(VPBA-co-EDMA) monolith. The effect of polymerization variables on the selectivity factor, e.g., the ratio of monomer to crosslinker (M/C), the amount of PS and the molecular weight of macromolecular porogen was investigated. The surface properties of the monolithic polymer were characterized by scanning electron microscopy and nitrogen adsorption. The best polymerization condition was the M/C ratio of 7:3, and the PS concentration of 40 mg/ml. The poly(VPBA-co-EDMA) polymer was also applied to extract cis-diol flavonoid glycosides from the crude extraction of cotton flower. After treated by poly(VPBA-co-EDMA) for solid phase extraction, high purity ISO and HYP (>99.96%) can be obtained with recovery of 83.7% and 78.6%, respectively. PMID- 26896915 TI - Home-made online hyphenation of pressurized liquid extraction, turbulent flow chromatography, and high performance liquid chromatography, Cistanche deserticola as a case study. AB - Incompatibility between the conventional pressurized liquid extraction (PLE) devices and high performance liquid chromatography (HPLC) extensively hinders direct and green chemical analysis of herbal materials. Herein, a facile PLE module was configured, and then it was online hyphenated with HPLC via a turbulent flow chromatography (TFC) column. Regarding PLE module, a long PEEK tube (0.13 * 1000 mm) was employed to generate desired pressure (approximately 13.0 MPa) when warm acidic water (70 degrees C) was delivered as extraction solvent at a high flow rate (2.5 mL/min), and a hollow guard column (3.0 * 4.0 mm) was implemented to hold crude materials. Effluent was collected from the outlet of PEEK tube, concentrated, and subjected onto HPLC coupled with hybrid ion trap-time of flight mass spectrometer to assess the extraction efficiency and also to profile the chemical composition of Cistanche deserticola (CD) that is honored as "Ginseng of the desert". Afterwards, a TFC column was introduced to accomplish online transmission of low molecule weight components from PLE module to HPLC coupled with diode array detection, and two electronic 6-port/2-channel valves were in charge of alternating the whole system between extraction (0-3.0 min) and elution (3.0-35.0 min) phases. Quantitative method was developed and validated for simultaneous determination of eight primary phenylethanoid glycosides in CD using online PLE-TFC-HPLC. All findings demonstrated that the home-made platform is advantageous at direct chemical analysis, as well as time-, solvent-, and material-savings, suggesting a robust tool for chemical fingerprinting of herbs. PMID- 26896916 TI - Crosslinked polymeric ionic liquids as solid-phase microextraction sorbent coatings for high performance liquid chromatography. AB - Neat crosslinked polymeric ionic liquid (PIL) sorbent coatings for solid-phase microextraction (SPME) compatible with high-performance liquid chromatography (HPLC) are reported for the first time. Six structurally different PILs were crosslinked to nitinol supports and applied for the determination of select pharmaceutical drugs, phenolics, and insecticides. Sampling conditions including sample solution pH, extraction time, desorption solvent, desorption time, and desorption solvent volume were optimized using design of experiment (DOE). The developed PIL sorbent coatings were stable when performing extractions under acidic pH and remained intact in various organic desorption solvents (i.e., methanol, acetonitrile, acetone). The PIL-based sorbent coating polymerized from the IL monomer 1-vinyl-3-(10-hydroxydecyl) imidazolium chloride [VC10OHIM][Cl] and IL crosslinker 1,12-di(3-vinylbenzylimidazolium) dodecane dichloride [(VBIM)2C12] 2[Cl] exhibited superior extraction performance compared to the other studied PILs. The extraction efficiency of pharmaceutical drugs and phenolics increased when the film thickness of the PIL-based sorbent coating was increased while many insecticides were largely unaffected. Satisfactory analytical performance was obtained with limits of detection (LODs) ranging from 0.2 to 2 MUg L(-1) for the target analytes. The accuracy of the analytical method was examined by studying the relative recovery of analytes in real water samples, including tap water and lake water, with recoveries varying from 50.2% to 115.9% and from 48.8% to 116.6%, respectively. PMID- 26896917 TI - Microscopic insight into role of protein flexibility during ion exchange chromatography by nuclear magnetic resonance and quartz crystal microbalance approaches. AB - Driven by the prevalent use of ion exchange chromatography (IEC) for polishing therapeutic proteins, many rules have been formulated to summarize the different dependencies between chromatographic data and various operational parameters of interest based on statically determined interactions. However, the effects of the unfolding of protein structures and conformational stability are not as well understood. This study focuses on how the flexibility of proteins perturbs retention behavior at the molecular scale using microscopic characterization approaches, including hydrogen-deuterium (H/D) exchange detected by NMR and a quartz crystal microbalance (QCM). The results showed that a series of chromatographic retention parameters depended significantly on the adiabatic compressibility and structural flexibility of the protein. That is, softer proteins with higher flexibility tended to have longer retention times and stronger affinities on SP Sepharose adsorbents. Tracing the underlying molecular mechanism using NMR and QCM indicated that an easily unfolded flexible protein with a more compact adsorption layer might contribute to the longer retention time on adsorbents. The use of NMR and QCM provided a previously unreported approach for elucidating the effect of protein structural flexibility on binding in IEC systems. PMID- 26896919 TI - Micellar and sub-micellar ultra-high performance liquid chromatography of hydroxybenzoic acid and phthalic acid positional isomers. AB - Micellar liquid chromatography (MLC) has been used primarily for the separation of neutral analytes of varying polarities, most commonly phenols and polyaromatic hydrocarbons, but does not seem to have been used to study aromatic hydroxy acids in detail. We have studied the separation of hydroxybenzoic acid mixtures, including monohydroxybenzoic and dihydroxybenzoic acid positional isomers by MLC. Sodium dodecylsulfate (SDS) is investigated as the modifying surfactant on a C18 ultra-high performance liquid chromatography (UHPLC) column (100 * 2.1mm, 1.8 MUm). The addition of only SDS (no organic solvent) to the mobile phase reduced the influence of hydrophobic interactions while improving the retention times, resolution, and peak shapes, even at concentrations below the critical micellization concentration (CMC). The UHPLC separation of 7 hydroxybenzoic acids, including 6 dihydroxybenzoic acid positional isomers and one trihydroxybenzoic acid, is achieved with high efficiency using 0.1% SDS in 1.84 mM sulfuric acid (pH 2.43) mobile phase, in less than 6 min with a flow rate of 0.3 mL min(-1), and in less than four min with a flow rate of 0.7 mL min(-1). Six monohydroxybenzoic acid isomers are also effectively separated by MLC, using a 0.5% SDS mobile phase modifier, in less than 20 min with a flow rate of 0.3 mL min(-1), and in less than 14 min with a flow rate of 0.7 mL min(-1). The 3 phthalic acid isomers could be separated using a similar mobile phase and flow rates in less than 6 and 4 min. Solute-micelle equilibrium constants and partition coefficients are calculated for 6 monohydroxybenzoic acids based on a plot of MLC retention factor vs. mobile phase micelle concentration. All aromatic acid isomers studied can be classified as binding solutes in the MLC retention mechanism. Less effective separations are observed with shorter chain surfactants, leading to higher retention times and poor peak shapes. It is concluded that increasing chain length led to more efficient MLC separations, and SDS is the preferred modifying surfactant for the examined separation. PMID- 26896918 TI - Enantiomeric profiling of chiral drug biomarkers in wastewater with the usage of chiral liquid chromatography coupled with tandem mass spectrometry. AB - This paper proposes a novel multi-residue enantioselective method utilising a CBH (cellobiohydrolase) column, for the analysis of 56 drug biomarkers in wastewater. These are: opioid analgesics, amphetamines, cocaine, heroin, stimulants, anaesthetics, sedatives, anxiolytics, designer drugs, phosphodiesterase-5 (PDE5) inhibitors, amphetamine and methamphetamine drug precursors. Satisfactory enantiomeric separation was obtained for 18 pairs of enantiomers including amphetamine, methamphetamine, MDMA (3,4-methylenedioxy-methamphetamine) and its metabolites HMA (4-hydroxy-3-methoxyamphetamine) and HMMA (4-hydroxy-3-methoxy methamphetamine), PMA (para-methoxyamphetamine), MDA ((+/-)- 3,4 methylenedioxyamphetamine) and mephedrone. The method was applied in a one week monitoring study of a large wastewater treatment plant in the UK. Most target drugs were found at quantifiable concentrations in analysed samples. Enantiomeric profiling revealed that amphetamine, methamphetamine and MDMA were found enriched with R-(-)-enantiomers, probably due to their stereoselective metabolism favouring S-(+)-enantiomers. MDA was either enriched with R-(-)- or S-(+) enantiomer indicating that its presence might be due to either abuse of racemic MDA or abuse of racemic MDMA respectively. Non-racemic enantiomeric fractions were also observed in the case of HMMA and mephedrone suggesting enantioselective metabolism. To the authors' knowledge, this is the first time chiral separation and wastewater profiling of mephedrone, PMA, MDMA and its metabolites HMA and HMMA have been reported. PMID- 26896920 TI - Investigating interactions between phospholipase B-Like 2 and antibodies during Protein A chromatography. AB - Purification processes for therapeutic antibodies typically exploit multiple and orthogonal chromatography steps in order to remove impurities, such as host-cell proteins. While the majority of host-cell proteins are cleared through purification processes, individual host-cell proteins such as Phospholipase B like 2 (PLBL2) are more challenging to remove and can persist into the final purification pool even after multiple chromatography steps. With packed-bed chromatography runs using host-cell protein ELISAs and mass spectrometry analysis, we demonstrated that different therapeutic antibodies interact to varying degrees with host-cell proteins in general, and PLBL2 specifically. We then used a high-throughput Protein A chromatography method to further examine the interaction between our antibodies and PLBL2. Our results showed that the co elution of PLBL2 during Protein A chromatography is highly dependent on the individual antibody and PLBL2 concentration in the chromatographic load. Process parameters such as antibody resin load density and pre-elution wash conditions also influence the levels of PLBL2 in the Protein A eluate. Furthermore, using surface plasmon resonance, we demonstrated that there is a preference for PLBL2 to interact with IgG4 subclass antibodies compared to IgG1 antibodies. PMID- 26896921 TI - Combined cation-exchange and solid phase extraction for the selective separation and preconcentration of zinc, copper, cadmium, mercury and cobalt among others using azo-dye functionalized resin. AB - A facile synthesis of an ion exchange material (FSG-PAN) has been achieved by functionalizing silica gel with an azo-dye. Its composition and structure are well assessed by systematic analysis. Extractor possesses high BET surface area (617.794m(2)g(-1)), exchange capacity and break-through capacity (BTC) (Q0 Zn(II): 225; Cd(II): 918; Hg(II): 384, Cu(II): 269 and Co(II): 388MUMg(-1)). The sorption process was endothermic (+DeltaH), entropy-gaining (+DeltaS) and spontaneous (-DeltaG) in nature. Preconcentration factor has been optimized at 172(Zn(II)); 157.2(Cd(II)); 193.6(Hg(II)); 176(Cu(II)); 172.4(Co(II)). Density functional theory calculation has been performed to analyze the sorption pathway. BTC (MUMg(-1)) of FSG-PAN was found to be the product of its frontier orbitals and state of sorbed metal ion species, x (at x=1, mononuclear and x>1, a polynuclear species; i.e., BTC=[amount of HOMO]*x). FSG-PAN is used for the selective separation and preconcentration of Zn(II), Cd(II), Hg(II), Cu(II),Co(II) from large volume sample (800mL) of low concentration (0.017 0.40mML(-1)) in presence of foreign ions (50-300mML(-1)) at optimum conditions (pH: 7.0+/-1.5, flow rate: 2.5mLmin(-1), temperature: 27 degrees C, equilibration time: 5min). The method was found to be effective for real samples also. PMID- 26896922 TI - Adverse events among COPD patients treated with long-acting anticholinergics and beta2-agonists in an outpatient respiratory clinic. AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in Canada. Most patients with COPD receive long-term treatment with long-acting anticholinergics (LAAC) and/or long-acting beta2-agonists (LABA). Adverse events (AEs) are also likely during long-term treatment with these medications. OBJECTIVE: To evaluate the prevalence of AEs in COPD patients on LAAC and LABA in a real-world setting. METHODS: We conducted a cross-sectional study of patients enrolled in the Registre de Donnees en Sante Pulmonaire (RESP) database, which records information on Canadian patients with asthma or COPD. COPD Patients completed a questionnaire about AEs that may be associated with LAAC and/or LABA. The prevalence of AEs and the corresponding 95% CI were calculated for three groups of patients (LAAC + LABA, LAAC alone, and LABA alone). RESULTS: Most patients with COPD (n = 154) were current or ex-smokers. Over 50% of patients were overweight or obese, and had an annual family income of less or equal to $42,000. Dry mouth (55.2%, 40%, and 43.5%) and dry throat (33.6%, 26.7%, and 34.8%) occurred most of the time or always in the LAAC + LABA, LAAC, and LABA groups, respectively. Headache was reported by 17.4% of patients in the LABA group, but less than 11.2% in the other groups. CONCLUSION: AEs reported in this study deserve clinical attention because they may negatively affect quality of life and treatment adherence of COPD patients. PMID- 26896923 TI - Successful tandem transplant in a young aplastic anemia patient from a small weight 11-month-old sibling donor. AB - Five years five month old male child diagnosed with aplastic anemia required blood and platelet support regularly. He was advised bone marrow transplant (BMT) and had 6/6 match with a younger sibling (11 months old). He was admitted for planned BMT and was put on preparatory regimen five days prior to BMT. GCSF primed bone marrow (BM) harvest was done from the donor, but the harvest was insufficient (1.05 * 10^6 /kg) and target dose of 4 million stem cells per kg could not be achieved. The BM harvest was infused into the patient and a repeat BM harvest was contemplated on next day. After careful evaluation of risks and benefits to the patient and the young donor, a decision to do a peripheral blood stem cell (PBSC) harvest was taken. The apheresis kit was blood primed to preclude possible hemodynamic imbalance in the donor considering low weight and young age. The entire harvest procedure (321 minutes) was uneventful with the donor remaining stable throughout. A dose of 2.40 million per kg of CD34+ cells was harvested and infused. Thus, a total dose of 3.45 million (1.05 BM and 2.4 PBSC) per kg was infused into the patient. Neutrophil and platelet engraftments and donor chimerism were achieved successfully with tandem BM-PBSC infusion and the patient continues to be disease free till 180 days follow up. This is possibly first published Indian report on BM-PBSC tandem transplant suggesting safety of PBSC harvests in small-weight young-age donor. PMID- 26896924 TI - Royal jelly supplementation in semen extender enhances post-thaw quality and fertility of Nili-Ravi buffalo bull sperm. AB - Two experiments were conducted to evaluate the effect of royal jelly (RJ) on post thaw sperm quality, in vitro and in vivo fertility rate of cryopreserved buffalo bull sperm. The semen was collected from three mature regular donor buffalo bulls, ejaculates were pooled and semen evaluated initially. In Experiment 1, the ejaculates were extended in tris-citric acid diluter supplemented with different RJ concentrations (0, 0.05, 0.1, 0.2, 0.3 or 0.4%). The diluted semen was cooled to 4 degrees C, packaged into 0.5 mL straws and frozen using standard procedure. The straws were thawed and assessed for sperm progressive motility, viability, plasma membrane, acrosome, and chromatin integrity. The results indicated that sperm progressive motility was significantly greater (P<0.05) in 0.05, 0.1, 0.2 and 0.3% RJ than 0.4% RJ supplemented and control groups. The sperm viability, plasma membrane and acrosome integrity were significantly improved (P<0.05) in 0.1% RJ supplemented group the compared to other treatment groups. In Experiment 2, cryopreserved sperm with 0.1% RJ supplementation and control (without RJ supplementation) were used to observe the in vitro fertilizing potential and in vivo fertility. In vitro fertilization method was applied to assess the cleavage rate; whereas, AI was performed in buffalo during in vivo fertility trial. The buffaloes were inseminated 12h after standing estrus and pregnancy diagnosis was performed through ultrasonography. The results revealed that the cleavage rate was higher (P<0.05) in 0.1% RJ as compared to control group. However, the pregnancy rate was similar (P>0.05) between 0.1% RJ supplemented and control groups. It is concluded that supplementation of RJ in freezing extender can improve the cryosurvival rate and in vitro fertilizing capacity of buffalo bull sperm. PMID- 26896925 TI - Swimming training attenuates the morphological reorganization of the myocardium and local inflammation in the left ventricle of growing rats with untreated experimental diabetes. AB - Diabetic cardiomyopathy is associated with cardiac remodeling, myocardial dysfunction, low-grade inflammation, and reduced cardiac adiponectin in patients with type 1 diabetes mellitus (T1DM). Alternatively, physical exercise is an important strategy for the management of diabetes. This study aimed to investigate the influence of low-intensity swimming training in cardiac cytokines, structural remodeling, and cardiomyocyte contractile dysfunction in growing rats with untreated experimental DM. Thirty-day-old male Wistar rats were divided into four groups (n=14, per group): sedentary control (SC), exercised control (EC), sedentary diabetic (SD), and exercised diabetic (ED). Diabetes was induced by streptozotocin (60 mg kg(-1), i.p.). Animals from exercised groups swam (5 days/week, 90 min/day, loading up to 5% body weight around the animal's chest) for 8 weeks. The left ventricle (LV) was removed for molecular, morphological, and cardiomyocyte mechanical analysis. Diabetic animals presented cardiac remodeling with myocardial histoarchitectural disorganization, fibrosis, and necrosis. The capillary density was lower in diabetic animals. LV cardiomyocytes from diabetic animals exhibited more prolonged time to the peak of contraction and time to half relaxation than those from control animals. The cardiac levels of interleukin 10, nitric oxide, and total and high molecular weight (HMW) adiponectin were significantly decreased in diabetic animals. Exercise training reduced the level of TNF-alpha, increased capillary density, and attenuated the histopathological parameters assessed in diabetic rats. In conclusion, the cardiac structural remodeling coexists with reduced levels of total and HMW adiponectin, inflammation, and cardiomyocyte contractility dysfunction in experimental DM. More important, low-intensity swimming training attenuates part of these pathological changes, indicating the beneficial role for exercise in untreated T1DM. PMID- 26896928 TI - Redefining radiology through clinical imaging. PMID- 26896927 TI - Are HLA-E*0103 alleles predictive markers for nasopharyngeal cancer risk? AB - BACKGROUND: Nasopharyngeal carcinoma (NPC) is a particular entity of head neck cancer, tightly related to Epstein-Barr virus infection and thus to HLA genes. In this study, we aimed to analyze HLA-E polymorphism in NPC advent and prognosis. 130 unrelated patients with CNP and 180 unrelated and healthy controls were included in our study. HLA-E genotyping was performed by PCR/RFLP method; SPSS (13.0) was used for statistical analysis, and survival curbs were established with the "Kaplan-Meier" method (Log Rank<0.05). RESULTS: We found a significant difference within HLA-E*103 variants between patients and controls: E*1031 and E*1032 were associated with CNP (OR=1.613, p=0.013 and OR=1.0809, p=0.055), and E*1033 with controls (OR=0.254, p<10(-4)). CONCLUSION: Our study reveals that HLA E polymorphism is associated with nasopharyngeal cancer. HLA-E expression studies could be used to understand the implication of E*103 variants. PMID- 26896926 TI - CCAAT/enhancer binding protein beta (C/EBPbeta) regulates the transcription of growth arrest and DNA damage-inducible protein 45 beta (GADD45beta) in articular chondrocytes. AB - Osteoarthritis (OA) is a whole joint disease characterized by cartilage degradation, which causes pain and disability in older adults. Our previous work showed that growth arrest and DNA damage-inducible protein 45 beta (GADD45beta) is upregulated in chondrocyte clusters in OA cartilage, especially in the early stage of this disease. CCAAT/enhancer binding protein beta (C/EBPbeta) is expressed in the hypertrophic growth plate chondrocytes and functions in synergy with GADD45beta. Here, the presence and localization of these proteins was assessed by immunohistochemistry using articular cartilage from OA patients, revealing colocalization of C/EBPbeta and GADD45beta in OA chondrocytes. GADD45beta promoter analysis was performed to determine whether C/EBPbeta directly regulates GADD45beta transcription. Furthermore, we analyzed the effect of C/EBPbeta on Gadd45beta gene regulation in articular chondrocytes in vivo and in vitro. Immunohistochemical analysis of C/ebpbeta-haploinsufficient mice (C/ebpbeta(+/-)) cartilage showed that C/ebpbeta haploinsufficiency led to reduced Gadd45beta gene expression in these cells. In vitro, we evaluated the effects of conditional C/EBPbeta overexpression driven by the cartilage oligomeric matrix protein (Comp) promoter in mComp-tTA;pTRE-Tight-BI-DsRed mC/ebpbeta transgenic mice. C/EBPbeta overexpression significantly stimulated Gadd45beta gene expression in articular chondrocytes. Taken together, our data demonstrate that C/EBPbeta plays a central role in controlling Gadd45beta gene expression in these cells. PMID- 26896929 TI - High fidelity simian immunodeficiency virus reverse transcriptase mutants have impaired replication in vitro and in vivo. AB - The low fidelity of HIV replication facilitates immune and drug escape. Some reverse transcriptase (RT) inhibitor drug-resistance mutations increase RT fidelity in biochemical assays but their effect during viral replication is unclear. We investigated the effect of RT mutations K65R, Q151N and V148I on SIV replication and fidelity in vitro, along with SIV replication in pigtailed macaques. SIVmac239-K65R and SIVmac239-V148I viruses had reduced replication capacity compared to wild-type SIVmac239. Direct virus competition assays demonstrated a rank order of wild-type>K65R>V148I mutants in terms of viral fitness. In single round in vitro-replication assays, SIVmac239-K65R demonstrated significantly higher fidelity than wild-type, and rapidly reverted to wild-type following infection of macaques. In contrast, SIVmac239-Q151N was replication incompetent in vitro and in pigtailed macaques. Thus, we showed that RT mutants, and specifically the common K65R drug-resistance mutation, had impaired replication capacity and higher fidelity. These results have implications for the pathogenesis of drug-resistant HIV. PMID- 26896930 TI - Characterization of Enterococcus faecium bacteriophage IME-EFm5 and its endolysin LysEFm5. AB - Due to the worldwide prevalence of antibiotic resistant strains, phages therapy has been revitalized recently. In this study, an Enterococcus faecium phage named IME-EFm5 was isolated from hospital sewage. Whole genomic sequence analysis demonstrated that IME-EFm5 belong to the Siphoviridae family, and has a double stranded genome of 42,265bp (with a 35.51% G+C content) which contains 70 putative coding sequences. LysEFm5, the endolysin of IME-EFm5, contains an amidase domain in its N-terminal and has a wider bactericidal spectrum than its parental phage IME-EFm5, including 7 strains of vancomycin-resistant E. faecium. The mutagenesis analysis revealed that the zinc ion binding residues (H27, H132, and C140), E90, and T138 are required for the catalysis of LysEFm5. However, the antibacterial activity of LysEFm5 is zinc ion independent, which is inconsistent with most of other amidase members. The phage lysin LysEFm5 might be an alternative treatment strategy for infections caused by multidrug-resistant E. faecium. PMID- 26896931 TI - Local persistence and global dissemination play a significant role in the circulation of influenza B viruses in Leyte Island, Philippines. AB - The local and global transmission dynamics of influenza B virus is not completely understood mainly because of limited epidemiological and sequence data for influenza B virus. Here we report epidemiological and molecular characteristics of influenza B viruses from 2010 to 2013 in Leyte Island, Philippines. Phylogenetic analyses showed global dissemination of the virus among both neighboring and distant areas. The analyses also suggest that southeast Asia is not a distributor of influenza B virus and can introduce the virus from other areas. Furthermore, we found evidence on the local persistence of the virus over years in the Philippines. Taken together, both local persistence and global dissemination play a significant role in the circulation of influenza B virus. PMID- 26896932 TI - Analysis of HCV-6 isolates among Asian-born immigrants in North America reveals their high genetic diversity and a new subtype. AB - We characterized full-length genomes for 15 HCV-6 isolates, all from Asian immigrants living in North America. Among these isolates, nine were novel variants showing >15% nucleotide differences from their nearest relatives, representing lineages distinct from known subtypes. The other six were classified into subtypes 6c, 6h, 6q, 6r, and 6s. The partial sequences were also determined for five additional HCV-6 isolates, three from the US and two from Canada. The latter two were assigned to new subtype 6xf as they were found to classify with two other isolates for which we recently reported their full-length genomes. We further analyzed partial Core-E1 sequences of 100 HCV-6 isolates sampled in North America, seven from the US and 93 from Canada and all from Asian immigrants except for four from Caucasians. These 100 isolates belonged to 20 assigned subtypes and 16 unclassified lineages showing great genetic diversity and enhanced significance to public health. PMID- 26896933 TI - A microRNA from infectious spleen and kidney necrosis virus modulates expression of the virus-mock basement membrane component VP08R. AB - Infectious spleen and kidney necrosis virus (ISKNV) is the type species of the genus Megalocytivirus, family Iridoviridae. Infection of ISKNV is characterized by a unique pathological phenomenon in that the infected cells are attached by lymphatic endothelial cells (LECs). ISKNV mediates the formation of a virus-mock basement membrane (VMBM) structure on the surface of infected cells to provide attaching sites for LECs. The viral protein VP08R is an important component of VMBM. In this study, a novel ISKNV-encoded microRNA, temporarily named ISKNV-miR 1, was identified. ISKNV-miR-1 is complementary to the VP08R-coding sequence and can modulate VP08R expression through reducing its mRNA level. This suggests that formation of VMBM may be under fine regulation by ISKNV. PMID- 26896934 TI - Role of Jumonji C-domain containing protein 6 (JMJD6) in infectivity of foot-and mouth disease virus. AB - Foot-and-mouth disease virus (FMDV) utilizes four integrins (alphavbeta1, alphavbeta3, alphavbeta6, and alphavbeta8) as its primary cell receptor. During cell culture propagation, FMDV frequently adapts to use heparan sulfate (HS), and rarely utilizes an unidentified third receptor. Capsid mutations acquired by a soluble integrin resistant FMDV cause (i) adaptation to CHO-677 cells (ii) increased affinity to membrane-bound Jumonji C-domain containing protein 6 (JMJD6) (iii) induced JMJD6 re-localization from the cell surface and cytoplasm to the nucleus. Interestingly, pre-treatment of cells with N- and C-terminal JMJD6 antibodies or by simultaneous incubation of mutant virus with soluble JMJD6 (but not by treatment with HS or alphavbeta6) impaired virus infectivity in cultured cells. JMJD6 and mutant virus co-purified by reciprocal co immunoprecipitation. Molecular docking predictions suggested JMJD6 C-terminus interacts with mutated VP1 capsid protein. We conclude when specific VP1 mutations are displayed, JMJD6 contributes to FMDV infectivity and may be a previously unidentified FMDV receptor. PMID- 26896936 TI - Building a Culture of Continuous Quality Improvement in an Academic Radiology Department. AB - As we enter a new era of health care in the United States, radiologists must be adequately prepared to prove, and continually improve, our value to our customers. This goal can be achieved in large part by providing high-quality services. Although quality efforts on the national and international levels provide a framework for improving radiologic quality, some of the greatest opportunities for quality improvement can be found at the departmental level, through the implementation of total quality management programs. Establishing such a program requires not only strong leadership and employee engagement, but also a firm understanding of the multiple total quality management tools and continuous quality improvement strategies available. In this article, we discuss key tools and strategies required to build a culture of continuous quality improvement in an academic department, based on our experience. PMID- 26896935 TI - The E glycoprotein plays an essential role in the high pathogenicity of European Mediterranean IS98 strain of West Nile virus. AB - West Nile virus (WNV) is the most widespread arbovirus in the world. Several recent outbreaks and epizootics have been reported in Europe and the Mediterranean basin with increased virulence. In contrast to the well characterized American and Australian strains, little is known about the virulence determinants of the WNV European-Mediterranean strains. To investigate the viral factors involved in the virulence of these strains, we generated chimeras between the highly neuropathogenic Israel 1998 (IS-98-ST1, IS98) strain and the non-pathogenic Malaysian Kunjin virus (KJMP-502). In vivo analyses in a mouse model of WNV pathogenesis shows that chimeric virus where KJMP-502 E glycoprotein was replaced by that of IS98 is neuropathogenic, demonstrating that this protein is a major virulence determinant. Presence of the N-glycosylation site had limited impact on virus virulence and the 5'UTR does not seem to influence pathogenesis. Finally, mice inoculated with KJMP-502 virus were protected against lethal IS98 infection. PMID- 26896937 TI - Sometimes It Takes a Village-Reducing Retained Surgical Items Through Multidisciplinary Collaboration. PMID- 26896938 TI - Skeletal muscle transcriptional profiles in two Italian beef breeds, Chianina and Maremmana, reveal breed specific variation. AB - Chianina and Maremmana breeds play an important role in the Italian cattle meat market. The Chianina breed is an ancient breed principally raised for draught. Now this breed is the worldwide recognized producer of top quality beef, tasteful and tender, specifically the famous "Florentine steak". The Maremmana characterized by a massive skeletal structure, is a rustic cattle breed selected for adaptability to the marshy land of the Maremma region. We used a high throughput mRNA sequencing to analyze gene expression in muscle tissues of two Italian cattle breeds, Maremmana (MM) and Chianina (CN) with different selection history. We aim to examine the specific genetic contribution of each breed to meat production and quality, comparing the skeletal muscle tissue from Maremmana and Chianina. Most of the differentially expressed genes were grouped in the Glycolysis/Gluconeogenesis pathways. The rate and the extent of post-mortem energy metabolism have a critical effect on the conversion of muscle to meat. Furthermore, we aim at discovering the differences in nucleotide variation between the two breeds which might be attributable to the different history of selection/divergence. In this work we could emphasize the involvement of pathways of post-mortem energy metabolism. Moreover, we detected a collection of coding SNPs which could offer new genomic resources to improve phenotypic selection in livestock breeding program. PMID- 26896939 TI - The five glucose-6-phosphatase paralogous genes are differentially regulated by insulin alone or combined with high level of amino acids and/or glucose in trout hepatocytes. AB - A recent analysis of the newly sequenced rainbow trout (Oncorhynchus mykiss) genome suggested that duplicated gluconeogenic g6pc paralogues, fixed in this genome after the salmonid-specific 4th whole genome duplication, may have a role in the setting up of the glucose-intolerant phenotype in this carnivorous species. This should be due to the sub- or neo-functionalization of their regulation. In the present short communication we thus addressed the question of the regulation of these genes by insulin, hormone involved in the glucose homeostasis, and its interaction with glucose and amino acids in vitro. The stimulation of trout hepatocytes with insulin revealed an atypical up-regulation of g6pcb2 ohnologues and confirmed the sub- or neo-functionalization of the five g6pc genes at least at the regulatory level. Intriguingly, when hepatocytes were cultured with high levels of glucose and/or AAs in presence of insulin, most of the g6pc paralogues were up-regulated. It strongly suggested a cross-talk between insulin and nutrients for the regulation of these genes. Moreover these results strengthened the idea that g6pc duplicated genes may significantly contribute to the setting up of the glucose-intolerant phenotype in trout via their atypical regulation by insulin alone or in interaction with nutrients. These findings open new perspectives to better understand in vivo glucose-intolerant phenotype in trout fed a high carbohydrate diet. PMID- 26896940 TI - Larvae of Ixodes ricinus transmit Borrelia afzelii and B. miyamotoi to vertebrate hosts. AB - BACKGROUND: Lyme borreliosis is the most common tick-borne human disease and is caused by Borrelia burgdorferi sensu lato (s.l.). Borrelia miyamotoi, a relapsing fever spirochaete, is transmitted transovarially, whereas this has not been shown for B. burgdorferi (s.l). Therefore, B. burgdorferi (s.l) is considered to cycle from nymphs to larvae through vertebrates. Larvae of Ixodes ricinus are occasionally B. burgdorferi (s.l) infected, but their vector competence has never been studied. METHODS: We challenged 20 laboratory mice with field-collected larvae of I. ricinus. A subset of these larvae was analysed for infections with B. burgdorferi (s.l) and B. miyamotoi. After three to four challenges, mice were sacrificed and skin and spleen samples were analysed for infection by PCR and culture. RESULTS: Field-collected larvae were naturally infected with B. burgdorferi (s.l) (0.62%) and B. miyamotoi (2.0%). Two mice acquired a B. afzelii infection and four mice acquired a B. miyamotoi infection during the larval challenges. CONCLUSION: We showed that larvae of I. ricinus transmit B. afzelii and B. miyamotoi to rodents and calculated that rodents have a considerable chance of acquiring infections from larvae compared to nymphs. As a result, B. afzelii can cycle between larvae through rodents. Our findings further imply that larval bites on humans, which easily go unnoticed, can cause Lyme borreliosis and Borrelia miyamotoi disease. PMID- 26896941 TI - Drug-related mortality among inpatients: a retrospective observational study. AB - PURPOSE: Hospital mortality related to adverse drug reactions (ADRs) is a relevant clinical problem with major health and economic consequences. We conducted a study to assess hospital mortality related to ADRs, the drugs most frequently involved, and the possible risk factors associated with fatal ADRs. METHODS: A retrospective observational study was conducted, reviewing the clinical records of 1388 consecutive adult patients (18-101 years) who died during a 22-month period in a tertiary hospital in Southern Europe (Granada, Spain). The main outcome was the prevalence of hospital death suspected to be related to administered drugs. RESULTS: Out of the 1388 adult deaths studied, 256 (18.4 %) were suspected of being related to drugs. Drugs were suspected of causing death in 146 inpatients (10.5 %) and contributing to death in 110 (7.9 %). Drugs related to death were administered during the hospital stay in 161 cases (11.5 %) and before hospital admission in 95 (6.84 %). The most frequent fatal ADRs were cardiac arrhythmia, gastrointestinal bleeding, and respiratory failure. The drugs most frequently involved in fatal ADRs were antithrombotics (anticoagulants or antiplatelets) (23 %), psychotropic drugs (21.2 %), and digoxin (11.3 %). Independent risk factors for ADR-related death were the presence of >=4 diseases (OR = 1.43) and the receipt of >=10 drugs (OR = 3.24), but no significant association with gender or age was found. CONCLUSIONS: A high percentage of hospital deaths were suspected of being associated with ADRs, especially in patients with comorbidity and/or polypharmacy. Antithrombotics, psychotropics, and digoxin were the drugs most frequently associated with in hospital drug-related deaths. PMID- 26896942 TI - Journal of Artificial Organs 2015: the year in review : Journal of Artificial Organs Editorial Committee. PMID- 26896943 TI - The effect of surgery (Ovariohysterectomy) on the plasma disposition of meloxicam following intravenous administration in dogs. AB - BACKGROUND: Meloxicam (MLX) is a nonsteroidal anti-inflammatory drug used in the relief of postoperative pain for human and veterinary medicine. This study was designed to investigate the effect of surgery on the plasma disposition of MLX in dogs undergoing ovariohysterectomy following a single intravenous injection at a dose of 0.2 mg/kg bodyweight. Eight crossbred bitches were used in the study. A two-phase experimental design with a 10-day washout period was used. Pre operative MLX was administered intravenously to 8 bitches about 10 days before surgery (Phase I, control) at a dose of 0.2 mg/kg bodyweight and peri-operative MLX was administered intravenously after anaesthesia and 15 min before the start of surgery (Phase II). Blood samples were collected from all animals at various times between 1 and 96 h after the drug administrations in both phases. The drug concentrations were analysed using high performance liquid chromatography. RESULTS: The volume of plasma MLX distribution at steady-state (Vdss) of the control group (Vdss: 263.0 ml/kg) was significantly greater (P < 0.05) compared to that of the surgery group (Vdss: 149.3 ml/kg). The AUC values were higher (29.5 vs. 23.0 MUg.h(2)/ml) and the CL values were lower (7.7 vs. 10.5 ml.h/kg) in the surgery group compared to the control group, respectively, but differences were not significant. CONCLUSIONS: The results of the present study indicated that surgery could alter the plasma disposition of MLX and thus the drug efficacy and side effects such as gastrointestinal ulceration, unusual bleeding and loss of kidney function/failure when repeated doses are used. PMID- 26896944 TI - Pulsed radiofrequency on radial nerve under ultrasound guidance for treatment of intractable lateral epicondylitis. AB - Lateral epicondylitis is a painful and functionally limiting disorder. Although lateral elbow pain is generally self-limiting, in a minority of people symptoms persist for a long time. When various conservative treatments fail, surgical approach is recommended. Surgical denervation of several nerves that innervate the lateral humeral epicondyle could be considered in patients with refractory pain because it denervates the region of pain. Pulsed radiofrequency is a minimally invasive procedure that improves chronic pain when applied to various neural tissues without causing any significant destruction and painful complication. This procedure is safe, minimally invasive, and has less risk of complications relatively compared to the surgical approach. The radial nerve can be identified as a target for pulsed radiofrequency lesioning in lateral epicondylitis. This innovative method of pulsed radiofrequency applied to the radial nerve has not been reported before. We reported on two patients with intractable lateral epicondylitis suffering from elbow pain who did not respond to nonoperative treatments, but in whom the ultrasound-guided pulsed radiofrequency neuromodulation of the radial nerve induced symptom improvement. After a successful diagnostic nerve block, radiofrequency probe adjustment around the radial nerve was performed on the lateral aspect of the distal upper arm under ultrasound guidance and multiple pulsed treatments were applied. A significant reduction in pain was reported over the follow-up period of 12 weeks. PMID- 26896945 TI - Fluoroscopically guided tunneled trans-caudal epidural catheter technique for opioid-free neonatal epidural analgesia. AB - Epidural analgesia confers significant perioperative advantages to neonates undergoing surgical procedures but may be very technically challenging to place using a standard interlaminar loss-of-resistance to saline technique given the shallow depth of the epidural space. Thoracic epidural catheters placed via the caudal route may reduce the risk of direct neural injury from needle placement, but often pose higher risks of infection and/or improper positioning if placed without radiographic guidance. We present a detailed method of placing a fluoroscopically guided, tunneled transcaudal epidural catheter, which may reduce both of these risks. The accuracy and precision of this technique often provides adequate analgesia to allow for opioid-free epidural infusions as well as significant reductions in systemic opioids through the perioperative period. Opioid-free analgesia using a regional anesthetic technique allows for earlier extubation and reduced perioperative sedation, which may have a less deleterious neurocognitive effect on the developing brain of the neonate. PMID- 26896946 TI - The Role of Acupuncture in Pain Management. AB - Acupuncture is a traditional Chinese practice of medicine that has gained popularity in Western culture and around the world. It involves the insertion of thin needles into the skin to stimulate nerves, muscles, and connective tissues throughout the body with the goal of alleviating pain, tension, and stress. More broadly, acupuncture is actually a family of different procedures. Conceptually, it is believed to stimulate the body's meridians, or energy-carrying channels, in an attempt to correct imbalances and to restore health. These benefits are thought to be derived from the proximity of acupoints with nerves through intracellular calcium ions. This lesson outlines a brief history of acupuncture and how it may be used to treat various types of physical and emotional pain and specific conditions, including overactive bladder and psoriasis. Acupuncture has been demonstrated to enhance endogenous opiates, such as dynorphin, endorphin, encephalin, and release corticosteroids, relieving pain and enhancing the healing process. There are associated risks; however, serious side effects are rare. When compared to traditional methods of pain management, more studies are warranted in order to establish the efficacy of acupuncture and its place in pain management. PMID- 26896948 TI - Facial Pain Update: Advances in Neurostimulation for the Treatment of Facial Pain. AB - Craniofacial pain, including trigeminal neuralgia, trigeminal neuropathic pain, and persistent idiopathic facial pain, is difficult to treat and can have severe implications for suffering in patients afflicted with these conditions. In recent years, clinicians have moved beyond treating solely with pharmacological therapies, which are generally not very effective, and focused on new interventional pain procedures. These procedures have evolved as technology has advanced, and thus far, early results have demonstrated efficacy in small patient cohorts with a variety of craniofacial pain states. Some of the most promising interventional pain procedures include peripheral nerve field stimulation, high frequency spinal cord stimulation, sphenopalatine ganglion stimulation, and deep brain stimulation. This review focuses on a better understanding of craniofacial pain and emerging interventional pain therapies. With the advent of newer miniature wireless devices and less invasive implantation techniques, this should allow for more widespread use of neurostimulation as a therapeutic modality for treating craniofacial pain. Larger studies should assist in best practice strategies vis-a-vis traditional pharmacological therapies and emerging interventional pain techniques. PMID- 26896947 TI - Pain in the Elderly. AB - Pain management in the elderly has increasingly become problematic in the USA as the aged population grows. The proportion of the population over 65 continues to climb and may eclipse 20 % in the next decade. In order to effectively diagnosis and treat these patients, a proper history and physical exam remain essential; pain assessment scales such as the Verbal Descriptor Scales (VDS), the Numerical Rating Scales (NRS), and the Visual Analogue Scales (VAS) often but not always prove beneficial. The conditions most frequently afflicting this population include osteoarthritis, diabetic neuropathy, post-herpetic neuralgia, and lower back pain which include spondylosis and radiculopathies. While the normal aging process does not necessarily guarantee symptoms of chronic pain, elderly individuals are far more likely to develop these painful conditions than their younger counterparts. There are many effective treatment modalities available as potential therapeutic interventions for elderly patients, including but not limited to analgesics such as NSAIDs and opioids, as well as multiple interventional pain techniques. This review will discuss chronic pain in the elderly population, including epidemiology, diagnostic tools, the multitude of co morbidities, and common treatment modalities currently available to physicians. PMID- 26896949 TI - Impact of element pitch on synthetic aperture ultrasound imaging. AB - PURPOSE: Synthetic aperture imaging was introduced in medical ultrasound to obtain high-quality images. In synthetic aperture ultrasound imaging, spherical transmit waves illuminate a target region from different positions, resulting in low-resolution images for each transmission. By coherent compounding of the resulting low-resolution images, a high-resolution image is obtained. Multiple steered receiving beams need to be created to obtain each low-resolution image and, thus, grating lobes should influence the image quality. In the present study, an array ultrasonic probe with a small element pitch was introduced to reduce the influences of grating lobes, and the effect of element pitch on image quality was examined in detail. METHOD: A linear array ultrasonic probe at a nominal center frequency of 7.5 MHz with an element pitch of 0.1 mm has been introduced. This probe does not produce grating lobes within the imaging region in theory because the element pitch of this probe is half of the ultrasonic wavelength. The contrast of an ultrasonic image was evaluated using a cyst phantom. RESULTS: The contrasts obtained by synthetic aperture imaging with element pitches of 0.1 and 0.2 mm were 4.88 and 4.69 dB, respectively, which were similar to the 4.67 dB obtained by conventional beamforming with focused transmit beams, when the number of transmissions was 121. The contrast obtained with an element pitch of 0.1 mm was similar (4.34 dB) even when the number of transmissions was decreased to 61. However, the contrast obtained with an element pitch of 0.2 mm showed a larger degradation (3.77 dB) at 31 transmissions. DISCUSSION AND CONCLUSION: Even with larger element pitches, good image contrast could be obtained when the number of transmissions was large. This is because echoes from grating lobes are incoherent among transmissions, and they are suppressed by compounding low-resolution images obtained by individual transmissions. On the other hand, an array probe with smaller element pitches achieves good image contrast even with a smaller number of transmissions and, thus, it would be preferable to realize a higher frame rate. PMID- 26896950 TI - Cis regulatory motifs and antisense transcriptional control in the apicomplexan Theileria parva. AB - BACKGROUND: Theileria parva is an intracellular parasite that causes a lymphoproliferative disease in cattle. It does so by inducing cancer-like phenotypes in the host cells it infects, although the molecular and regulatory mechanisms involved remain poorly understood. RNAseq data, and the resulting updated genome annotation now available for this parasite, offer an unprecedented opportunity to characterize the genomic features associated with gene regulation in this species. Our previous analyses revealed a T. parva genome even more gene dense than previously thought, with many adjacent loci overlapping each other, not only at the level of untranslated sequences (UTRs) but even in coding sequences. RESULTS: Despite this compactness, Theileria intergenic regions show a pattern of size distribution indicative of monocistronic gene transcription. Three previously described motifs are conserved among Theileria species and highly prevalent in promoter regions near or at the transcription start sites. We found novel motifs at many transcription termination sites, as well as upstream of parasite genes thought to be critical for host transformation. Adjacent genes that could be regulated by antisense transcription from an overlapping transcriptional unit are syntenic between T. parva and P. falciparum at a frequency higher than expected by chance, suggesting the presence of common, and evolutionary old, regulatory mechanisms in the phylum Apicomplexa. CONCLUSIONS: We propose a model of transcription with conserved sense and antisense transcription from a few taxonomically ubiquitous and several species-specific promoter motifs. Interestingly, the gene networks regulated by conserved promoters are themselves, in most cases, not conserved between species or genera. PMID- 26896952 TI - Evaluation of anticancer properties of a decoction containing Adenanthera pavonina L. and Thespesia populnea L. AB - BACKGROUND: A decoction composed of Adenanthera pavonina L. and Thespesia populnea L. is currently being used in the treatment of cancer patients. METHODS: Lactate Dehydrogenase (LDH) release, (3-(4, 5-Dimethylthiazol-2-yl)-2, 5 diphenyltetrazolium bromide) MTT, and Sulforhodamine B (SRB) assays were carried out to study cytotoxicity and anti-proliferative activity against the HEp-2 cells, 24 h post-treatment with the decoction. RESULTS: The mean (+/- SD) values of EC50 were 195.50 (+/-40.68), 120.02 (+/-29.82) and 77.06 (+/-8.80) MUg/ml for LDH, MTT, and SRB assays respectively. These results strongly correlate the morphological changes observed in cells treated with the decoction. Induction of apoptosis was visualized by fluorescence microscopy stained with ethidium bromide/acridine orange dye mix. In addition, brine shrimp lethality assay showed an EC50 value at a higher concentration (1.96 mg/mL). CONCLUSIONS: These results suggest that the decoction prepared with Adenanthera pavonina L. and Thespesia populnea L. exhibits anti-proliferative activity and induces apoptosis on the HEp 2 cancer cells but no toxicity against Artemia salina. PMID- 26896954 TI - Upper gastrointestinal hemorrhage caused by a giant polyp of the esophagus. PMID- 26896953 TI - Reciprocal interaction between dental alloy biocorrosion and Streptococcus mutans virulent gene expression. AB - Corrosion of dental alloys is a major concern in dental restorations. Streptococcus mutans reduces the pH in oral cavity and induces demineralization of the enamel as well as corrosion of restorative dental materials. The rough surfaces of dental alloys induced by corrosion enhance the subsequent accumulation of plaque. In this study, the corrosion process of nickel-chromium (Ni-Cr) and cobalt-chromium (Co-Cr) alloys in a nutrient-rich medium containing S. mutans was studied using inductively coupled plasma atomic emission spectrometry (ICP-AES), X-ray photoelectron spectroscopy (XPS) and electrochemical corrosion test. Our results showed that the release of Ni and Co ions increased, particularly after incubation for 3 days. The electrochemical corrosion results showed a significant decrease in the corrosion resistance (Rp) value after the alloys were immersed in the media containing S. mutans for 3 days. Correspondingly, XPS revealed a reduction in the relative dominance of Ni, Co, and Cr in the surface oxides after the alloys were immersed in the S. mutans culture. After removal of the biofilm, the pre-corroded alloys were re-incubated in S. mutans medium, and the expressions of genes associated with the adhesion and acidogenesis of S. mutans, including gtfBCD, gbpB, fif and ldh, were evaluated by detecting the mRNA levels using real-time reverse transcription polymerase chain reaction (RT-PCR). We found that the gtfBCD, gbpB, ftf and Idh expression of S. mutans were noticeably increased after incubation with pre corroded alloys for 24 h. This study demonstrated that S. mutans enhanced the corrosion behavior of the dental alloys, on the other hand, the presence of corroded alloy surfaces up-regulated the virulent gene expression in S. mutans. Compared with smooth surfaces, the rough corroded surfaces of dental alloys accelerated the bacteria-adhesion and corrosion process by changing the virulence gene expression of S. mutans. PMID- 26896951 TI - The Mental Health of Elite Athletes: A Narrative Systematic Review. AB - BACKGROUND: The physical impacts of elite sport participation have been well documented; however, there is comparatively less research on the mental health and psychological wellbeing of elite athletes. OBJECTIVE: This review appraises the evidence base regarding the mental health and wellbeing of elite-level athletes, including the incidence and/or nature of mental ill-health and substance use. METHODS: A systematic search of the PubMed, EMBASE, SPORTDiscus, PsycINFO, Cochrane and Google Scholar databases, up to and including May 2015, was conducted. RESULTS: The search yielded a total of 2279 records. Following double screening, 60 studies were included. The findings suggested that elite athletes experience a broadly comparable risk of high-prevalence mental disorders (i.e. anxiety, depression) relative to the general population. Evidence regarding other mental health domains (i.e. eating disorders, substance use, stress and coping) is less consistent. These results are prefaced, however, by the outcome of the quality assessment of the included studies, which demonstrated that relatively few studies (25 %) were well reported or methodologically rigorous. Furthermore, there is a lack of intervention-based research on this topic. CONCLUSION: The evidence base regarding the mental health and wellbeing of elite athletes is limited by a paucity of high-quality, systematic studies. Nonetheless, the research demonstrates that this population is vulnerable to a range of mental health problems (including substance misuse), which may be related to both sporting factors (e.g. injury, overtraining and burnout) and non sporting factors. More high-quality epidemiological and intervention studies are needed to inform optimal strategies to identify and respond to player mental health needs. PMID- 26896956 TI - The mind-muscle connection in resistance training: friend or foe? AB - The results of Calatayud et al. (Eur J Appl Physiol, 2015. doi: 10.1007/s00421 015-3305-7 ) indicate that focusing on the pectoralis major and triceps brachii muscles during bench press exercise selectively enhanced their activation, and thus suggest a training strategy. However, the authors did not discuss the well established negative effects that focusing on specific muscle groups has on exercise performance. For proper perspective of the results and their practical utility, it is helpful to note the interplay between negative and positive effects of different focus conditions. PMID- 26896955 TI - Targeted next-generation sequencing of locally advanced squamous cell carcinomas of the head and neck reveals druggable targets for improving adjuvant chemoradiation. AB - BACKGROUND: Despite clear differences in clinical presentation and outcome, squamous cell carcinomas of the head and neck (SCCHN) arising from human papilloma virus (HPV) infection or heavy tobacco/alcohol consumption are treated equally. Next-generation sequencing is expected to reveal novel targets for more individualised treatment. PATIENTS AND METHODS: Tumour specimens from 208 patients with locally advanced squamous cell carcinoma of the hypopharynx, oropharynx or oral cavity, all uniformly treated with adjuvant cisplatin-based chemoradiation, were included. A customised panel covering 211 exons from 45 genes frequently altered in SCCHN was used for detection of non-synonymous point and frameshift mutations. Mutations were correlated with HPV status and treatment outcome. RESULTS: Mutational profiles and HPV status were successfully established for 179 cases. HPV- tumours showed an increased frequency of alterations in tumour suppressor genes compared to HPV+ cases (TP53 67% versus 4%, CDKN2A 18% versus 0%). Conversely, HPV+ carcinomas were enriched for activating mutations in driver genes compared to HPV- cases (PIK3CA 30% versus 12%, KRAS 6% versus 1%, and NRAS 4% versus 0%). Hotspot TP53 missense mutations in HPV- carcinomas correlated with an increased risk of locoregional recurrence (hazard ratio [HR] 4.3, 95% confidence interval [CI] 1.5-12.1, P=0.006) and death (HR 2.2, 95% CI 1.1-4.4, P=0.021). In HPV+ SCCHN, driver gene mutations were associated per trend with a higher risk of death (HR 3.9, 95% CI 0.7-21.1, P=0.11). CONCLUSIONS: Distinct mutation profiles in HPV- and HPV+ SCCHN identify subgroups with poor outcome after adjuvant chemoradiation. Mutant p53 and the phosphoinositide 3-kinase pathway were identified as potential druggable targets for subgroup-specific treatment optimisation. PMID- 26896957 TI - Mind-muscle connection revisited: do 100 studies about beanbag tossing, stick balancing, and dart throwing have any relevance for strength training? PMID- 26896958 TI - The effects and determinants of exercise participation in first-episode psychosis: a qualitative study. AB - BACKGROUND: Previous qualitative studies have found that exercise may facilitate symptomatic and functional recovery in people with long-term schizophrenia. This study examined the perceived effects of exercise as experienced by people in the early stages of psychosis, and explored which aspects of an exercise intervention facilitated or hindered their engagement. METHODS: Nineteen semi-structured interviews were conducted with early intervention service users who had participated in a 10-week exercise intervention. Interviews discussed people's incentives and barriers to exercise, short- and long-term effects, and opinions on optimal interventions. A thematic analysis was applied to determine the prevailing themes. RESULTS: The intervention was perceived as beneficial and engaging for participants. The main themes were (a) exercise alleviating psychiatric symptoms, (b) improved self-perceptions following exercise, and (c) factors determining exercise participation, with three respective sub-themes for each. CONCLUSIONS: Participants explained how exercise had improved their mental health, improved their confidence and given them a sense of achievement. Autonomy and social support were identified as critical factors for effectively engaging people with first-episode psychosis in moderate-to-vigorous exercise. Implementing such programs in early intervention services may lead to better physical health, symptom management and social functioning among service users. TRIAL REGISTRATION: Current Controlled Trials ISRCTN09150095. Registered 10 December 2013. PMID- 26896959 TI - Over-expression of cathepsin B in hepatocellular carcinomas predicts poor prognosis of HCC patients. AB - BACKGROUND: Several studies have found that Cathepsin B (CTSB) is up-regulated in many tumor types and facilitates tumor progression. However, the role of CTSB in hepatocellular carcinoma (HCC) progression remains unclear. This study was aimed at investigating the expression and role of CTSB in HCC in a large set of samples and cell lines (MHCC-97H and MHCC-97 L), and evaluating the clinical and prognostic significance of CTSB protein in patients with HCC. METHODS: The expression of CTSB was examined in HCC tissue and cell lines by Western-blotting, Real-time PCR, and immunohistochemical staining. Wound healing assay and invasion assay were used to verify the effect of CTSB on the migration and invasion ability of HCC cell lines. Tumor formation assay in nude mice was used to analyze the effect of CTSB on the tumorigenicity of HCC cell lines. RESULTS: The status of CTSB protein in carcinoma tissues is much higher than that in paracarcinoma tissues. The overall survival of the patients with high CTSB expression was significantly shorter than the low CTSB expression group. High CTSB expression was significantly correlated with advanced clinical staging, histological grade, and tumor recurrence. In vitro and in vivo experiments demonstrated that over expression of CTSB in MHCC-97 L cells promoted cell invasion and tumor progression ability. Down-regulation of CTSB in MHCC-97H showed the opposite effects. These phenotypic changes caused by CTSB knockdown or over-expression correlated with expression of the matrix metallopeptidase MMP-9. Moreover, multivariate analysis suggested that CTSB expression might be an independent prognostic indicator for the survival of HCC patients after curative surgery. CONCLUSIONS: CTSB might be involved in the development and progression of HCC as an oncogene, and thereby may be a valuable prognostic marker for HCC patients. PMID- 26896961 TI - Long-term health-related quality of life in eating disorders. AB - OBJECTIVE: There is limited evidence on the long-term development of health related quality of life (HRQoL) in eating disorders and its relation to eating disorder symptoms. Our objective was to measure long-term change in the HRQoL of eating disorder patients and compare it to normal population. METHODS: Fifty-four bulimia nervosa (BN) and forty-seven anorexia nervosa (AN) patients (ICD-10 diagnosis) entering treatment completed the 15D HRQoL questionnaire and the Eating Disorder Inventory (EDI) before and approximately 8 years after the start of treatment. RESULTS: Baseline HRQoL was severely impaired in the patients. During follow-up, mean HRQoL, body mass index (BMI) and EDI improved statistically significantly in both groups. BMI of AN patients reached normal values, but HRQoL was still severely impaired in both AN and BN compared to general population. CONCLUSIONS: The long-term HRQoL after treatment continues to improve, but is still after 8 years poor. Eating disorders are very serious conditions with long-lasting impact on quality of life even after symptom remission. PMID- 26896960 TI - Impact of a community-based lifestyle intervention program on health-related quality of life. AB - BACKGROUND: The presence of risk factors for type 2 diabetes and cardiovascular disease, or the conditions themselves, contributes to lower health-related quality of life (HRQoL) among adults. Although community-based lifestyle intervention programs have been shown to be effective for improving risk factors for these diseases, the impact of these interventions on HRQoL has rarely been described. PURPOSE: To examine changes in HRQoL following participation in the Group Lifestyle Balance program, a community translation of the Diabetes Prevention Program lifestyle intervention for adults with prediabetes and/or the metabolic syndrome. METHODS: Participants enrolled in the 12-month, 22-session intervention program (N = 223) completed the EuroQol Health Questionnaire (EQ-5D 3L) at baseline, 6, and 12 months. Linear mixed-effects regression models determined change in EQ-5D-visual analog scale (VAS) and Index scores post intervention. RESULTS: Mean EQ-5D-VAS was improved by +7.38 (SE = 1.03) at 6 months and by +6.73 (SE = 1.06) at 12 months post-intervention (both; p < 0.0001). Mean changes in EQ-5D index values were +0.00 (SE = 0.01; NS) and +0.01 (SE = 0.01; p < 0.05), respectively. Adjusted for age, baseline score, and achieving intervention goals, mean change in EQ-5D-VAS was +11.83 (SE = 1.61) at 6 months and +11.23 (SE = 1.54) at 12 months (both; p < 0.0001). Adjusted mean change in EQ-5D index value was +0.04 (SE = 0.01) at 6 months and +0.05 (SE = 0.01) at 12 months (both; p < 0.01). CONCLUSION: Participation in a community lifestyle intervention program resulted in improved HRQoL among adults with prediabetes and/or the metabolic syndrome. These benefits to HRQoL, together with improved clinical and behavioral outcomes, should increase the appeal of such programs for improving health. PMID- 26896962 TI - Seeking treatment for uncomplicated malaria: experiences from the Kintampo districts of Ghana. AB - BACKGROUND: Malaria accounts for many deaths and illnesses, mostly among young children and pregnant women in sub-Saharan Africa. An integrated approach is recommended to ensure effective malaria control. Socio-cultural factors continue to serve as determinants of malaria health-seeking behaviour. An INDEPTH effectiveness and safety study platform was established to unearth issues around the use of licensed and nationally recommended anti-malarials in real life settings. This study reports on treatment-seeking behaviour for uncomplicated malaria among community members. METHODS: A qualitative study was conducted in the dry and rainy seasons in purposively selected communities in Kintampo north and south districts. This was based on distances to a health facility, ethnicity and availability of medicines at the sale outlets. Twenty-four focus group discussions were conducted among adult men, women care-takers of children less than 5 years and pregnant women. Ten INDEPTH interviews were also conducted among operators of medicine sale outlets and managers of health facilities. Fifty-one illnesses narrative interviews were conducted among adult men, women, women caretakers of children less than 5 years and pregnant women. Transcripts were transferred into Nvivo 8 software for data management and analysis. RESULTS: The artemisinin-based combinations that were commonly known and used were artesunate amodiaquine and artemether-lumefantrine. Use of herbal preparation to treat diseases including uncomplicated malaria is rife in the communities. Drug stores were not the main source of artemisinin-based combination sales at time of the study. Monotherapies, pain killers and other medicines were purchased from these shops for malaria treatment. Dizziness, general body weakness and sleepiness were noted among respondents who used artemisinin-based combination therapy (ACT) in the past. CONCLUSION: There is no clear cut trajectory for management of uncomplicated malaria in the study area. Different approaches are adopted when treating malaria. There is need for community education to influence behaviour on the management of malaria to achieve real gains from ACT use. PMID- 26896964 TI - Understanding parental refusal of permission for child participation in surgical prospective trials. AB - PURPOSE: The success of prospective randomized trials relies on voluntary participation, which has been perceived as a barrier for successful trials in children who rely on parental permission. We sought to identify the reasons parents decline child participation to understand potential limitations in the consent process. METHODS: A prospective observational study was conducted in 92 patients asked to participate in prospective randomized trials between 2012 and 2015. Parental reasons for refusal were documented. RESULTS: The 92 refusals were distributed between studies investigating the management of circumcision, gastroschisis, pectus excavatum, appendicitis, pyloric stenosis, undescended testicles, abdominal abscess and gastroesophageal reflux. Reasons for refusal included preference of treatment path (37 %), inability to follow up (21 %), unspecified resistance to participate in research (18 %), preference to maintain independent surgeon decision (16 %), and desire for historically standard treatment (8 %). Of the families who opted to pursue a specific treatment arm rather than randomization, 35 % had prior experience with that treatment, 32 % had researched the procedure, 18 % wished to pursue the minimal intervention and 15 % did not specify. CONCLUSIONS: Parental preference of therapy is the most common reason for refusal of study participation. This variable could be influenced with more effective explanation of study rationale and existing equipoise. PMID- 26896963 TI - Phase II trial of biweekly docetaxel, cisplatin, and 5-fluorouracil chemotherapy for advanced esophageal squamous cell carcinoma. AB - The prognosis of esophageal cancer patients is still unsatisfactory. Although a docetaxel, cisplatin, and 5-Fu (DCF) regimen has been reported, it is often difficult to accomplish because of severe toxicity. Therefore, we developed a new biweekly DCF (Bi-DCF) regimen and previously reported the recommended dose in a phase I dose-escalation study. We then performed a phase II study of Bi-DCF for advanced esophageal squamous cell carcinoma (SCC). Patients with clinical stage II/III were eligible. Patients received 2 courses of chemotherapy: docetaxel 35 mg/m(2) with cisplatin 40 mg/m(2) on days 1 and 15 and 400 mg/m(2) 5-fluorouracil on days 1-5 and 15-19 every 4 weeks. After completion of the chemotherapy, patients received esophagectomy. The primary endpoint was the completion rate of protocol treatment. Thirty-two patients were enrolled. The completion rate of protocol treatment (completion of two courses of preoperative chemotherapy and R0 surgery) was 100 %. During chemotherapy, the most common grade 3 or 4 toxicities were neutropenia (31.3 %). No treatment-related death was observed, and the incidence of operative morbidity was tolerable. The overall response rate after the chemotherapy was 90.3 %. This Bi-DCF regimen was well tolerated and highly active. This trial was registered with the University Hospital Medical Information Network (No. UMIN 000014625). PMID- 26896965 TI - Inherent variability in lead and copper collected during standardized sampling. AB - Variability in the concentration of lead and copper sampled at consumers' taps poses challenges to assessing consumer health threats and the effectiveness of corrosion control. To examine the minimum variability that is practically achievable, standardized rigs with three lead and copper containing plumbing materials (leaded brass, copper tube with lead solder, and a lead copper connection) were deployed at five utilities and sampled with regimented protocols. Variability represented by relative standard deviation (RSD) in lead release was high in all cases. The brass had the lowest variability in lead release (RSD = 31 %) followed by copper-solder (RSD = 49%) and lead-copper (RSD = 80%). This high inherent variability is due to semi-random detachment of particulate lead to water, and represents a modern reality of water lead problems that should be explicitly acknowledged and considered in all aspects of exposure, public education, and monitoring. PMID- 26896967 TI - Sand dredging and environmental efficiency of artisanal fishermen in Lagos state, Nigeria. AB - Environmentally detrimental input (water turbidity) and conventional production inputs were considered within the framework of stochastic frontier analysis to estimate technical and environmental efficiencies of fishermen in sand dredging and non-dredging areas. Environmental efficiency was low among fishermen in the sand dredging areas. Educational status and experience in fishing and sand dredging were the factors influencing environmental efficiency in the sand dredging areas. Average quantity of fish caught per labour- hour was higher among fishermen in the non-dredging areas. Fishermen in the fishing community around the dredging areas travelled long distance in order to reduce the negative effect of sand dredging on their fishing activity. The study affirmed large household size among fishermen. The need to regulate the activities of sand dredgers by restricting license for sand dredging to non-fishing communities as well as intensifying family planning campaign in fishing communities to reduce the negative effect of high household size on fishing is imperative for the sustainability of artisanal fishing. PMID- 26896966 TI - The effects of wildfire on mercury and stable isotopes (delta(15)N, delta(13)C) in water and biota of small boreal, acidic lakes in southern Norway. AB - Effects of wildfire on main water chemistry and mercury (Hg) in water and biota were studied during the first 4 post-fire years. After severe water chemical conditions during hydrological events a few months following the wildfire, the major water chemical parameters were close to pre-fire conditions 4 years after the fire. Concentrations of total Hg and methyl Hg in the surface water 4 years after the fire ranged between 1.17-2.63 ng L(-1) and 0.053-0.188 ng L(-1), respectively. Both variables were positive and strongly correlated with total organic carbon (TOC), TOC-related variables (color, UV absorbance), total phosphorous, and total iron. In addition, MeHg was positively correlated with total nitrogen and chlorophyll-a. The concurrence of increased concentrations of nutrients and chlorophyll-a in the lakes, the more enriched delta(15)N-signatures and higher Hg levels in fish 2 years after the fire, might be a result of the wildfire. However, natural factors as year-to-year variations in thermocline depth and suboxic status in the lakes make it difficult to draw any strong conclusions about wildfire effects on Hg in the biota from our investigated lakes. PMID- 26896969 TI - Communication: Determination of relativistic effects from X-ray structure factors. AB - In this communication, a procedure is presented which allows for the determination of the scalar-relativistic contraction of individual electronic shells of transition metal atoms from X-ray structure factor data. The procedure is verified and benchmarked employing theoretical and experimental F(hkl) data, revealing an overall good agreement between the experimentally determined results and the theoretical reference values. From the experimental data, the relativistic contraction of the n = 2 shell of a cerium atom is, for example, determined as 0.097 pm, compared to a theoretical reference value of 0.116 pm. It is further demonstrated that the reproducibility of the results is excellent when comparing different experimental data sets. Finally, the dependency of the according results on the data resolution of the structure factor data is investigated. PMID- 26896970 TI - Excitation energy-transfer in functionalized nanoparticles: Going beyond the Forster approach. AB - We develop a novel approach to treat excitation energy transfer in hybrid nanosystems composed by an organic molecule attached to a semiconductor nanoparticle. Our approach extends the customary Forster theory by considering interaction between transition multipole moments of the nanoparticle at all orders and a point-like transition dipole moment representing the molecule. Optical excitations of the nanoparticle are described through an envelope function configuration interaction method for a single electron-hole pair. We applied the method to the prototypical case of a core/shell CdSe/ZnS semiconductor quantum dot which shows a complete suppression of the energy transfer for specific transitions which could not be captured by Forster theory. PMID- 26896968 TI - Sustained virological response after a 17-day treatment with daclatasvir plus asunaprevir in a cirrhotic patient with hepatitis C virus genotype 1b and null response for peginterferon ribavirin therapy. AB - Daclatasvir (DCV) plus asunaprevir (ASV) treatment, an oral therapy for chronic hepatitis C virus (HCV) genotype 1b infection, can achieve a high sustained viral response (SVR) rate within a 24-week treatment period. A 55-year-old Japanese female with cirrhosis and null response for peginterferon plus ribavirin therapy received DCV plus ASV therapy, but she reported a slight fever beginning on treatment day 4. The fever increased to >38.0 degrees C beginning on treatment day 15 and could not be controlled with antipyretics; thus, the treatment was discontinued on day 17. Although the patient was still positive for HCV RNA 6 days after treatment discontinuation, she achieved an SVR at week 24 after treatment cessation. In some patients with HCV genotype 1b infection, an SVR can be achieved with short-term DCV plus ASV treatment, and HCV RNA positivity at the end of treatment does not always indicate virological failure. PMID- 26896971 TI - Reconciling perturbative approaches in phonon-assisted transport junctions. AB - We present consistent results for molecular conduction using two central complementary approaches: the non-equilibrium Green's function technique and the quantum master equation method. Our model describes electronic conduction in a donor-acceptor junction in which electron transfer is coupled to nuclear motion, modeled by a harmonic vibrational mode. This primary mode is further coupled to secondary phonon modes, a thermal bath. Assuming weak electron-phonon coupling but an arbitrary large molecule-metal hybridization, we compute several non equilibrium transport quantities: the mean phonon number of the primary mode, charge current statistics. We further present scaling relations for the cumulants valid in the large voltage regime. Our analysis illustrates that the non equilibrium Green's function technique and the quantum master equation method can be worked out consistently, when taking into account corresponding scattering processes. PMID- 26896972 TI - Internally contracted multireference coupled-cluster theory in a multistate framework. AB - The internally contracted multireference coupled cluster (icMRCC) theory is reexamined in a multistate framework. The new derivation starts from the Bloch equations employing a wave operator similar to the one originally employed by Jeziorski and Monkhorst [Phys. Rev. A 24, 1668 (1981)], but allows for a multideterminantal model-space basis. The resulting working equations are a generalization of state-universal multireference coupled-cluster (SU-MRCC) theory. In the case of truncated cluster operators, energies and wave functions depend on the choice of the model-space basis. It is shown that the state specific solutions of the original icMRCC theory exactly diagonalize the effective Hamiltonian of the multistate theory and thus decouple the multistate equations. While this in principle means that icMRCC is a multistate theory, we find that truncated icMRCC theory still shows minor artifacts close to avoided crossings, which can be removed by considering a true multistate ansatz. The results also shed new light on the orbital variance of the original SU-MRCC theory. PMID- 26896973 TI - Stochastic averaging and sensitivity analysis for two scale reaction networks. AB - In the presence of multiscale dynamics in a reaction network, direct simulation methods become inefficient as they can only advance the system on the smallest scale. This work presents stochastic averaging techniques to accelerate computations for obtaining estimates of expected values and sensitivities with respect to the steady state distribution. A two-time-scale formulation is used to establish bounds on the bias induced by the averaging method. Further, this formulation provides a framework to create an accelerated "averaged" version of most single-scale sensitivity estimation methods. In particular, we propose the use of a centered ergodic likelihood ratio method for steady state estimation and show how one can adapt it to accelerated simulations of multiscale systems. Finally, we develop an adaptive "batch-means" stopping rule for determining when to terminate the micro-equilibration process. PMID- 26896974 TI - A numerical efficient way to minimize classical density functional theory. AB - The minimization of the functional of the grand potential within the framework of classical density functional theory in three spatial dimensions can be numerically very demanding. The Picard iteration, that is often employed, is very simple and robust but can be rather slow. While a number of different algorithms for optimization problems have been suggested, there is still great need for additional strategies. Here, we present an approach based on the limited memory Broyden algorithm that is efficient and relatively simple to implement. We demonstrate the performance of this algorithm with the minimization of an inhomogeneous bulk structure of a fluid with competing interactions. For the problems we studied, we find that the presented algorithm improves performance by roughly a factor of three. PMID- 26896976 TI - Dissipation in monotonic and non-monotonic relaxation to equilibrium. AB - Using molecular dynamics simulations, we study field free relaxation from a non uniform initial density, monitored using both density distributions and the dissipation function. When this density gradient is applied to colour labelled particles, the density distribution decays to a sine curve of fundamental wavelength, which then decays conformally towards a uniform distribution. For conformal relaxation, the dissipation function is found to decay towards equilibrium monotonically, consistent with the predictions of the relaxation theorem. When the system is initiated with a more dramatic density gradient, applied to all particles, non-conformal relaxation is seen in both the dissipation function and the Fourier components of the density distribution. At times, the system appears to be moving away from a uniform density distribution. In both cases, the dissipation function satisfies the modified second law inequality, and the dissipation theorem is demonstrated. PMID- 26896975 TI - Validation of local hybrid functionals for TDDFT calculations of electronic excitation energies. AB - The first systematic evaluation of local hybrid functionals for the calculation of electronic excitation energies within linear-response time-dependent density functional theory (TDDFT) is reported. Using our recent efficient semi-numerical TDDFT implementation [T. M. Maier et al., J. Chem. Theory Comput. 11, 4226 (2015)], four simple, thermochemically optimized one-parameter local hybrid functionals based on local spin-density exchange are evaluated against a database of singlet and triplet valence excitations of organic molecules, and against a mixed database including also Rydberg, intramolecular charge-transfer (CT) and core excitations. The four local hybrids exhibit comparable performance to standard global or range-separated hybrid functionals for common singlet valence excitations, but several local hybrids outperform all other functionals tested for the triplet excitations of the first test set, as well as for relative energies of excited states. Evaluation for the combined second test set shows that local hybrids can also provide excellent Rydberg and core excitations, in the latter case rivaling specialized functionals optimized specifically for such excitations. This good performance of local hybrids for different excitation types could be traced to relatively large exact-exchange (EXX) admixtures in a spatial region intermediate between valence and asymptotics, as well as close to the nucleus, and lower EXX admixtures in the valence region. In contrast, the tested local hybrids cannot compete with the best range-separated hybrids for intra- and intermolecular CT excitation energies. Possible directions for improvement in the latter category are discussed. As the used efficient TDDFT implementation requires essentially the same computational effort for global and local hybrids, applications of local hybrid functionals to excited-state problems appear promising in a wide range of fields. Influences of current-density dependence of local kinetic-energy dependent local hybrids, differences between spin-resolved and "common" local mixing functions in local hybrids, and the effects of the Tamm-Dancoff approximation on the excitation energies are also discussed. PMID- 26896977 TI - FALCON: A method for flexible adaptation of local coordinates of nuclei. AB - We present a flexible scheme for calculating vibrational rectilinear coordinates with well-defined strict locality on a certain set of atoms. Introducing a method for Flexible Adaption of Local COordinates of Nuclei (FALCON) we show how vibrational subspaces can be "grown" in an adaptive manner. Subspace Hessian matrices are set up and used to calculate and analyze vibrational modes and frequencies. FALCON coordinates can more generally be used to construct vibrational coordinates for describing local and (semi-local) interacting modes with desired features. For instance, spatially local vibrations can be approximately described as internal motion within only a group of atoms and delocalized modes can be approximately expressed as relative motions of rigid groups of atoms. The FALCON method can support efficiency in the calculation and analysis of vibrational coordinates and energies in the context of harmonic and anharmonic calculations. The features of this method are demonstrated on a few small molecules, i.e., formylglycine, coumarin, and dimethylether as well as for the amide-I band and low-frequency modes of alanine oligomers and alpha conotoxin. PMID- 26896978 TI - Molecular electronic states near metal surfaces at equilibrium using potential of mean force and numerical renormalization group methods: Hysteresis revisited. AB - We investigate equilibrium observables for molecules near metals by employing a potential of mean force (PMF) that takes level broadening into account. Through comparison with exact data, we demonstrate that this PMF approach performs quite well, even for cases where molecule-electrode couplings depend on nuclear position. As an application, we reexamine the possibility of hysteresis effects within the Anderson-Holstein model (i.e., an impurity coupled both to a metal surface and a nuclear oscillator). As compared against the standard mean field approach by Galperin et al. [Nano Lett. 5, 125 (2005)], our PMF approach agrees much better with exact results for average electronic populations both at zero and finite temperature; we find, however, that mean field theory can be very useful for predicting the onset of dynamical instabilities, metastable states, and hysteresis. PMID- 26896979 TI - Simulating two-dimensional infrared-Raman and Raman spectroscopies for intermolecular and intramolecular modes of liquid water. AB - Full classical molecular dynamics (MD) simulations of two-dimensional (2D) infrared-Raman and 2D Raman spectroscopies of liquid water were carried out to elucidate a mode-mode coupling mechanism using a polarizable water model for intermolecular and intramolecular vibrational spectroscopy (POLI2VS). This model is capable of describing both infrared and Raman spectra. Second-order response functions, which consist of one molecular polarizability and two molecular dipole moments for 2D IR-Raman and three molecular polarizabilities for 2D Raman spectroscopies, were calculated using an equilibrium-non-equilibrium hybrid MD approach. The obtained signals were analyzed using a multi-mode Brownian oscillator (BO) model with nonlinear system-bath interactions representing the intramolecular OH stretching, intramolecular HOH bending, hydrogen bonded (HB) intermolecular librational motion and HB-intermolecular vibrational (translational) motion of liquid water. This model was applied through use of hierarchal Fokker-Planck equations. The qualitative features of the peak profiles in the 2D spectra obtained from the MD simulations are accurately reproduced with the BO model. This indicates that this model captures the essential features of the intermolecular and intramolecular motion. We elucidate the mechanisms governing the 2D signal profiles involving anharmonic mode-mode coupling, the nonlinearities of the polarizability and dipole moment, and the vibrational dephasing processes of liquid water even in the case that the 2D spectral peaks obtained from the MD simulation overlap or are unclear. The mode coupling peaks caused by electrical anharmonic coupling (EAHC) and mechanical anharmonic coupling (MAHC) are observed in all of the 2D spectra. We find that the strength of the MAHC between the OH-stretching and HB-intermolecular vibrational modes is comparable to that between the OH-stretching and HOH bending modes. Moreover, we find that this OH-stretching and HB-intermolecular vibrational coupling should be observed as off-diagonal cross peaks in the 2D spectra. PMID- 26896980 TI - Sub-Doppler infrared spectroscopy and formation dynamics of triacetylene in a slit supersonic expansion. AB - Infrared spectroscopy and formation dynamics of triacetylene are investigated in a slit jet supersonic discharge and probed with sub-Doppler resolution (~60 MHz) on the fundamental antisymmetric CH stretch mode (nu5). The triacetylene is generated in the throat of the discharge by sequential attack of ethynyl radical with acetyelene and diacetylene: (i) HCCH -> HCC + H, (ii) HCC + HCCH -> HCCCCH + H, (iii) HCC + HCCCCH -> HCCCCCCH + H, cooled rapidly in the slit expansion to 15 K, and probed by near shot-noise-limited absorption sensitivity with a tunable difference-frequency infrared laser. The combination of jet cooled temperatures (Trot = 15 K) and low spectral congestion permits (i) analysis of rotationally avoided crossings in the nu5 band ascribed to Coriolis interactions, as well as (ii) first detection of nu5 Pi-Pi hot band progressions built on the nu12 sym CC bend and definitively assigned via state-of-the-art ab initio vibration-rotation interaction parameters (alphai), which make for interesting comparison with recent spectroscopic studies of Doney et al. [J. Mol. Spectrosc. 316, 54 (2015)]. The combined data provide direct evidence for significantly non-equilibrium populations in the CC bending manifold, dynamically consistent with a strongly bent radical intermediate and transition states for forming triacetylene product. The presence of intense triacetylene signals under cold, low density slit jet conditions provides support for (i) barrierless addition of HCC with HCCCCH and (ii) a high quantum yield for HCCCCCCH formation. Complete basis set calculations for energetics [CCSD(T)-f12/VnZ-f12, n = 2,3] and frequencies [CCSD(T)-f12/VdZ f12] are presented for both radical intermediate and transition state species, predicting collision stabilization in the slit jet expansion to be competitive with unimolecular decomposition with increasing polyyne chain length. PMID- 26896981 TI - Calculated vibrational states of ozone up to dissociation. AB - A new accurate global potential energy surface for the ground electronic state of ozone [R. Dawes et al., J. Chem. Phys. 139, 201103 (2013)] was published fairly recently. The topography near dissociation differs significantly from previous surfaces, without spurious submerged reefs and corresponding van der Waals wells. This has enabled significantly improved descriptions of scattering processes, capturing the negative temperature dependence and large kinetic isotope effects in exchange reaction rates. The exchange reactivity was found to depend on the character of near-threshold resonances and their overlap with reactant and product wavefunctions, which in turn are sensitive to the potential. Here we present global "three-well" calculations of all bound vibrational states of three isotopic combinations of ozone ((48)O3, (16)O2 (18)O, (16)O2 (17)O) for J = 0 and J = 1 with a focus on the character and density of highly excited states and discuss their impact on the ozone isotopic anomaly. The calculations were done using a parallel symmetry-adapted Lanczos method with the RV3 code. Some comparisons were made with results obtained with the improved relaxation method implemented in the Heidelberg multi-configuration time-dependent Hartree code. PMID- 26896982 TI - Photoelectron spectra of 2-thiouracil, 4-thiouracil, and 2,4-dithiouracil. AB - Ground- and excited-state UV photoelectron spectra of thiouracils (2-thiouracil, 4-thiouracil, and 2,4-dithiouracil) have been simulated using multireference configuration interaction calculations and Dyson norms as a measure for the photoionization intensity. Except for a constant shift, the calculated spectrum of 2-thiouracil agrees very well with experiment, while no experimental spectra are available for the two other compounds. For all three molecules, the photoelectron spectra show distinct bands due to ionization of the sulphur and oxygen lone pairs and the pyrimidine pi system. The excited-state photoelectron spectra of 2-thiouracil show bands at much lower energies than in the ground state spectrum, allowing to monitor the excited-state population in time-resolved UV photoelectron spectroscopy experiments. However, the results also reveal that single-photon ionization probe schemes alone will not allow monitoring all photodynamic processes existing in 2-thiouracil. Especially, due to overlapping bands of singlet and triplet states the clear observation of intersystem crossing will be hampered. PMID- 26896983 TI - Characterizing the local solvation environment of OH(-) in water clusters with AIMD. AB - In this work, we use ab initio molecular dynamics coupled with metadynamics to explore and characterize the glassy potential energy landscape of the OH(-) in a 20 and 48 water cluster. The structural, energetic, and topological properties of OH(-) are characterized for both clusters and the molecular origins of the IR signatures are examined. We find that in both the small and large clusters, the OH(-) can donate or accept a varying number of hydrogen bonds confirming that the amphiphilic character does not depend on cluster size. However, we highlight some important differences found between the energetic and topological properties of both families of clusters which may have implications on understanding the changes in the solvation structure of OH(-) between bulk and interfacial environments. By studying the IR spectra of smaller subsets of molecules within the 20 water molecule cluster, we find that the IR spectrum of the bare OH(-) as well as the water molecule donating a strong hydrogen bond to it exhibits characteristic absorption along the amphiphilic band between 1500 and 3000 cm(-1) at positions very similar to those found for the entire hydroxide cluster. The results presented here will be useful in the calibration and improvement of both ab initio and semi-empirical methods to model this complex anion. PMID- 26896984 TI - Isotopomer-selective spectra of a single intact H2O molecule in the Cs(+)(D2O)5H2O isotopologue: Going beyond pattern recognition to harvest the structural information encoded in vibrational spectra. AB - We report the vibrational signatures of a single H2O molecule occupying distinct sites of the hydration network in the Cs(+)(H2O)6 cluster. This is accomplished using isotopomer-selective IR-IR hole-burning on the Cs(+)(D2O)5(H2O) clusters formed by gas-phase exchange of a single, intact H2O molecule for D2O in the Cs(+)(D2O)6 ion. The OH stretching pattern of the Cs(+)(H2O)6 isotopologue is accurately recovered by superposition of the isotopomer spectra, thus establishing that the H2O incorporation is random and that the OH stretching manifold is largely due to contributions from decoupled water molecules. This behavior enables a powerful new way to extract structural information from vibrational spectra of size-selected clusters by explicitly identifying the local environments responsible for specific infrared features. The Cs(+)(H2O)6 structure was unambiguously assigned to the 4.1.1 isomer (a homodromic water tetramer with two additional flanking water molecules) from the fact that its computed IR spectrum matches the observed overall pattern and recovers the embedded correlations in the two OH stretching bands of the water molecule in the Cs(+)(D2O)5(H2O) isotopomers. The 4.1.1 isomer is the lowest in energy among other candidate networks at advanced (e.g., CCSD(T)) levels of theoretical treatment after corrections for (anharmonic) zero-point energy. With the structure in hand, we then explore the mechanical origin of the various band locations using a local electric field formalism. This approach promises to provide a transferrable scheme for the prediction of the OH stretching fundamentals displayed by water networks in close proximity to solute ions. PMID- 26896985 TI - Transport coefficients of He(+) ions in helium. AB - This paper demonstrates that the transport coefficients of (4)He(+) in (4)He can be calculated over wide ranges of E/N, the ratio of the electrostatic field strength to the gas number density, with the same level of precision as can be obtained experimentally if sufficiently accurate potential energy curves are available for the X(2)Sigmau (+) and A(2)Sigmag (+) states and one takes into account resonant charge transfer. We start by computing new potential energy curves for these states and testing their accuracy by calculating spectroscopic values for the separate states. It is established that the potentials obtained by extrapolation of results from d-aug-cc-pVXZ (X = 6, 7) basis sets using the CASSCF+MRCISD approach are each in exceptionally close agreement with the best potentials available and with experiment. The potentials are then used in a new computer program to determine the semi-classical phase shifts and the transport cross sections, and from these the gaseous ion transport coefficients are determined. In addition, new experimental values are reported for the mobilities of (4)He(+) in (4)He at 298.7 K, as a function of E/N, where careful consideration is given to minimizing various sources of uncertainty. Comparison with previously measured values establishes that only one set of previous data is reliable. Finally, the experimental and theoretical ion transport coefficients are shown to be in very good to excellent agreement, once corrections are applied to account for quantum-mechanical effects. PMID- 26896987 TI - A two force-constant model for complexes B?M-X (B is a Lewis base and MX is any diatomic molecule): Intermolecular stretching force constants from centrifugal distortion constants D(J) or Delta(J). AB - A two force-constant model is proposed for complexes of the type B?MX, in which B is a simple Lewis base of at least C2v symmetry and MX is any diatomic molecule lying along a Cn axis (n >= 2) of B. The model assumes a rigid subunit B and that force constants beyond quadratic are negligible. It leads to expressions that allow, in principle, the determination of three quadratic force constants F11, F12, and F22 associated with the r(B?M) = r2 and r(M-X) = r1 internal coordinates from the equilibrium centrifugal distortion constants DJ (e) or DeltaJ (e), the equilibrium principal axis coordinates a1 and a2, and equilibrium principal moments of inertia. The model can be applied generally to complexes containing different types of intermolecular bond. For example, the intermolecular bond of B?MX can be a hydrogen bond if MX is a hydrogen halide, a halogen-bond if MX is a dihalogen molecule, or a stronger, coinage-metal bond if MX is a coinage metal halide. The equations were tested for BrCN, for which accurate equilibrium spectroscopic constants and a complete force field are available. In practice, equilibrium values of DJ (e) or DeltaJ (e) for B?MX are not available and zero point quantities must be used instead. The effect of doing so has been tested for BrCN. The zero-point centrifugal distortion constants DJ (0) or DeltaJ (0) for all B?MX investigated so far are of insufficient accuracy to allow F11 and F22 to be determined simultaneously, even under the assumption F12 = 0 which is shown to be reasonable for BrCN. The calculation of F22 at a series of fixed values of F11 reveals, however, that in cases for which F11 is sufficiently larger than F22, a good approximation to F22 is obtained. Plots of F22 versus F11 have been provided for Kr?CuCl, Xe?CuCl, OC?CuCl, and C2H2?AgCl as examples. Even in cases where F22 ~ F11 (e.g., OC?CuCl), such plots will yield either F22 or F11 if the other becomes available. PMID- 26896986 TI - Role of weakly bound complexes in temperature-dependence and relative rates of M(x)O(y)(-) + H2O (M = Mo, W) reactions. AB - Results of a systematic comparison of the MoxOy (-) + H2O and WxOy (-) + H2O reaction rate coefficients are reported and compared to previous experimental and computational studies on these reactions. WxOy (-) clusters undergo more direct oxidation by water to yield WxOy+1 (-) + H2, while for MoxOy (-) clusters, production of MoxOyH2 (-) (trapped intermediates in the oxidation reaction) is comparatively more prevalent. However, MoxOy (-) clusters generally have higher rate coefficients than analogous WxOy (-) clusters if MoxOy+1H2 (-) formation is included. Results of calculations on the M2Oy (-) + H2O (M = Mo, W; y = 4, 5) reaction entrance channel are reported. They include charge-dipole complexes formed from long-range interactions, and the requisite conversion to a Lewis acid base complex that leads to MxOy+1H2 (-) formation. The results predict that the Lewis acid-base complex is more strongly bound for MoxOy (-) clusters than for WxOy (-) clusters. The calculated free energies along this portion of the reaction path are also consistent with the modest anti-Arrhenius temperature dependence measured for most MoxOy (-) + H2O reactions, and the WxOy (-) + H2O reaction rate coefficients generally being constant over the temperature range sampled in this study. For clusters that exhibit evidence of both water addition and oxidation reactions, increasing the temperature increases the branching ratio toward oxidation for both species. A more direct reaction path to H2 production may therefore become accessible at modest temperatures for certain cluster stoichiometries and structures. PMID- 26896988 TI - Tracking the photodissociation probability of D(2)(+) induced by linearly chirped laser pulses. AB - In the presence of linearly varying frequency chirped laser pulses, the photodissociation dynamics of D2(+) is studied theoretically after ionization of D2. As a completion of our recent work [A. Csehi et al., J. Chem. Phys. 143, 014305 (2015)], a comprehensive dependence on the pulse duration and delay time is presented in terms of total dissociation probabilities. Our numerical analysis carried out in the recently introduced light-induced conical intersection (LICI) framework clearly shows the effects of the changing position of the LICI which is induced by the frequency modulation of the chirped laser pulses. This impact is presented for positively, negatively, and zero chirped short pulses. PMID- 26896989 TI - Density measurements of subcooled water in the temperature range of (243 and 283) K and for pressures up to 400 MPa. AB - In this work, accurate density measurements of subcooled water (freshly double distilled water) were performed along eight constant-mass curves in the temperature range of (243 to 283) K and in the pressure range of (140 to 400) MPa, by a pseudo-isochoric method. The experimental apparatus mainly consisted of a high pressure vessel, especially designed for this experiment, of known volume as a function of temperature and pressure, used to perform measurements in the T p range under study. The density of subcooled water was obtained by measuring the equilibrium pressure at different temperatures, keeping the mass constant. All terms contributing to the uncertainty of subcooled water density measurements were considered; the estimated relative uncertainty, in the investigated temperature and pressure range, is about 0.07%. The experimental results were compared with the literature densities. In particular, the trend of density versus temperature for a constant mass of sample observed experimentally differs from the trend calculated by the equation provided by the International Association for Properties of Water and Steam (IAPWS-95) outside the range of validity, i.e., in the metastable region. PMID- 26896990 TI - Spontaneous cavitation in a Lennard-Jones liquid: Molecular dynamics simulation and the van der Waals-Cahn-Hilliard gradient theory. AB - The process of bubble nucleation in a Lennard-Jones (LJ) liquid is studied by molecular dynamics (MD) simulation. The bubble nucleation rate J is determined by the mean life-time method at temperatures above that of the triple point in the region of negative pressures. The results of simulation are compared with classical nucleation theory (CNT) and modified classical nucleation theory (MCNT), in which the work of formation of a critical bubble is determined in the framework of the van der Waals-Cahn-Hilliard gradient theory (GT). It has been found that the values of J obtained in MD simulation systematically exceed the data of CNT, and this excess in the nucleation rate reaches 8-10 orders of magnitude close to the triple point temperature. The results of MCNT are in satisfactory agreement with the data of MD simulation. To describe the properties of vapor-phase nuclei in the framework of GT, an equation of state has been built up which describes stable, metastable and labile regions of LJ fluids. The surface tension of critical bubbles gamma has been found from CNT and data of MD simulation as a function of the radius of curvature of the surface of tension R*. The dependence gamma(R*) has also been calculated from GT. The Tolman length has been determined, which is negative and in modulus equal to ~(0.1 - 0.2) sigma. The paper discusses the applicability of the Tolman formula to the description of the properties of critical nuclei in nucleation. PMID- 26896991 TI - Mode coupling theory and fragile to strong transition in supercooled TIP4P/2005 water. AB - We study by molecular dynamics simulations supercooled water with the TIP4P/2005 potential. This model is able to predict many properties of water in a large range of the thermodynamic space in agreement with experiments. We explore the dynamical behavior and, in particular, the self intermediate scattering function of the oxygen atoms. We find that the structural relaxation in the range of mild supercooling is in agreement with the Mode Coupling Theory (MCT). The ideal MCT crossover takes place at decreasing temperature with increasing density. Deviations from the MCT behavior are found upon further supercooling. A crossover from the MCT, fragile, regime to a strong, Arrhenius, regime is found and it is connected to the presence of a liquid-liquid phase transition and the Widom line emanating from the liquid-liquid critical point. PMID- 26896992 TI - Equilibrium structures of anisometric, quadrupolar particles confined to a monolayer. AB - We investigate the structural properties of a two-dimensional system of ellipsoidal particles carrying a linear quadrupole moment in their center. These particles represent a simple model for a variety of uncharged, non-polar conjugated organic molecules. Using optimization tools based on ideas of evolutionary algorithms, we first examine the ground state structures as we vary the aspect ratio of the particles and the pressure. Interestingly, we find, besides the intuitively expected T-like configurations, a variety of complex structures, characterized with up to three different particle orientations. In an effort to explore the impact of thermal fluctuations, we perform constant pressure molecular dynamics simulations within a range of rather low temperatures. We observe that ground state structures formed by particles with a large aspect ratio are in particular suited to withstand fluctuations up to rather high temperatures. Our comprehensive investigations allow for a deeper understanding of molecular or colloidal monolayer arrangements under the influence of a typical electrostatic interaction on a coarse-grained level. PMID- 26896994 TI - The electronic structure formation of Cu(x)TiSe2 in a wide range (0.04 < x < 0.8) of copper concentration. AB - An experimental study of the electronic structure of copper intercalated titanium dichalcogenides in a wide range of copper concentrations (x = 0.04-0.8) using x ray photoelectron spectroscopy, resonant photoelectron spectroscopy, and x-ray absorption spectroscopy has been performed. Shift towards low energies of the Ti 2p and Se 3d core level spectra and a corresponding decrease in the photon energy of Ti 2p absorption spectra with the increase in copper concentration have been found. These sign-anomalous shifts may be explained by the shielding effect of the corresponding atomic shells as a result of the dynamic charge transfer during the formation of a covalent chemical bond between the copper atoms and the TiSe2 matrix. PMID- 26896993 TI - Absolute vibrational cross sections for 1-19 eV electron scattering from condensed tetrahydrofuran (THF). AB - Absolute cross sections (CSs) for vibrational excitation by 1-19 eV electrons impacting on condensed tetrahydrofuran (THF) were measured with a high-resolution electron energy loss spectrometer. Experiments were performed under ultra-high vacuum (3 * 10(-11) Torr) at a temperature of about 20 K. The magnitudes of the vibrational CSs lie within the 10(-17) cm(2) range. Features observed near 4.5, 9.5, and 12.5 eV in the incident energy dependence of the CSs were compared to the results of theoretical calculations and other experiments on gas and solid phase THF. These three resonances are attributed to the formation of shape or core-excited shape resonances. Another maximum observed around 2.5 eV is not found in the calculations but has been observed in gas-phase studies; it is attributed to the formation of a shape resonance. PMID- 26896995 TI - A monolayer of hierarchical silver hemi-mesoparticles with tunable surface topographies for highly sensitive surface-enhanced Raman spectroscopy. AB - We proposed a facile green synthesis system to synthesize large-scale Ag hemi mesoparticles monolayer on Cu foil. Ag hemi-mesoparticles have different surface morphologies on their surfaces, including ridge-like, meatball-like, and fluffy like shapes. In the reaction, silver nitrate was reduced by copper at room temperature in dimethyl sulfoxide via the galvanic displacement reaction. The different surface morphologies of the Ag hemi-mesoparticles were adjusted by changing the reaction time, and the hemi-mesoparticle surface formed fluffy spherical nanoprotrusions at longer reaction time. At the same time, we explored the growth mechanism of silver hemi-mesoparticles with different surface morphologies. With 4-mercaptobenzoic acid as Raman probe molecules, the fluffy like silver hemi-mesoparticles monolayer with the best activity of surface enhanced Raman scattering (SERS), the enhancement factor is up to 7.33 * 10(7) and the detection limit can reach 10(-10)M. SERS measurements demonstrate that these Ag hemi-mesoparticles can serve as sensitive SERS substrates. At the same time, using finite element method, the distribution of the localized electromagnetic field near the particle surface was simulated to verify the enhanced mechanism. This study helps us to understand the relationship between morphology Ag hemi-mesoparicles and the properties of SERS. PMID- 26896997 TI - Tracking three-phase coexistences in binary mixtures of hard plates and spheres. AB - The stability of demixing phase transition in binary mixtures of hard plates (with thickness L and diameter D) and hard spheres (with diameter sigma) is studied by means of Parsons-Lee theory. The isotropic-isotropic demixing, which is found in mixtures of large spheres and small plates, is very likely to be pre empted by crystallization. In contrast, the nematic-nematic demixing, which is obtained in mixtures of large plates and small spheres, can be stabilized at low diameter ratios (sigma/D) and aspect ratios (L/D). At intermediate values of sigma/D, where the sizes of the components are similar, neither the isotropic isotropic nor the nematic-nematic demixing can be stabilized, but a very strong fractionation takes place between a plate rich nematic and a sphere rich isotropic phases. Our results show that the excluded volume interactions are capable alone to explain the experimental observation of the nematic-nematic demixing, but they fail in the description of isotropic-isotropic one [M. Chen et al., Soft Matter 11, 5775 (2015)]. PMID- 26896998 TI - Coarse-grained simulations of poly(propylene imine) dendrimers in solution. AB - The behavior of poly(propylene imine) (PPI) dendrimers in concentrated solutions has been investigated using molecular dynamics simulations containing up to a thousand PPI dendrimers of generation 4 or 5 in explicit water. To deal with large system sizes and time scales required to study the solutions over a wide range of dendrimer concentrations, a previously published coarse-grained model was applied. Simulation results on the radius of gyration, structure factor, intermolecular spacing, dendrimer interpenetration, and water penetration are compared with available experimental data, providing a clear concentration dependent molecular picture of PPI dendrimers. It is shown that with increasing concentration the dendrimer volume diminishes accompanied by a reduction of internalized water, ultimately resulting in solvent filled cavities between stacked dendrimers. Concurrently dendrimer interpenetration increases only slightly, leaving each dendrimer a separate entity also at high concentrations. Moreover, we compare apparent structure factors, as calculated in experimental studies relying on the decoupling approximation and the constant atomic form factor assumption, with directly computed structure factors. We demonstrate that these already diverge at rather low concentrations, not because of small changes in form factor, but rather because the decoupling approximation fails as monomer positions of separate dendrimers become correlated at concentrations well below the overlap concentration. PMID- 26896996 TI - Coupling of isotropic and directional interactions and its effect on phase separation and self-assembly. AB - The interactions of molecules and particles in solution often involve an interplay between isotropic and highly directional interactions that lead to a mutual coupling of phase separation and self-assembly. This situation arises, for example, in proteins interacting through hydrophobic and charged patch regions on their surface and in nanoparticles with grafted polymer chains, such as DNA. As a minimal model of complex fluids exhibiting this interaction coupling, we investigate spherical particles having an isotropic interaction and a constellation of five attractive patches on the particle's surface. Monte Carlo simulations and mean-field calculations of the phase boundaries of this model depend strongly on the relative strength of the isotropic and patch potentials, where we surprisingly find that analytic mean-field predictions become increasingly accurate as the directional interactions become increasingly predominant. We quantitatively account for this effect by noting that the effective interaction range increases with increasing relative directional to isotropic interaction strength. We also identify thermodynamic transition lines associated with self-assembly, extract the entropy and energy of association, and characterize the resulting cluster properties obtained from simulations using percolation scaling theory and Flory-Stockmayer mean-field theory. We find that the fractal dimension and cluster size distribution are consistent with those of lattice animals, i.e., randomly branched polymers swollen by excluded volume interactions. We also identify a universal functional form for the average molecular weight and a nearly universal functional form for a scaling parameter characterizing the cluster size distribution. Since the formation of branched clusters at equilibrium is a common phenomenon in nature, we detail how our analysis can be used in experimental characterization of such associating fluids. PMID- 26896999 TI - The effect of intermolecular interaction on excited states in p-DTS(FBTTH2)2. AB - Using optical spectroscopy in solution and thin film, and supported by quantum chemical calculations, we investigated the aggregation process of the donor acceptor type molecule p-DTS(FBTTH2)2. We demonstrate that cooling a solution induces a disorder-order phase transition that proceeds in three stages analogous to the steps observed in semi-rigid conjugated polymers. By analyzing the spectra, we are able to identify the spectral signature of monomer and aggregate in absorption and emission. From this we find that in films, the fraction of aggregates is near 100% which is in contrast to films made from semi-rigid conjugated polymers. PMID- 26897001 TI - Note: Brownian motion of colloidal particles of arbitrary shape. PMID- 26897000 TI - Markov state models of protein misfolding. AB - Markov state models (MSMs) are an extremely useful tool for understanding the conformational dynamics of macromolecules and for analyzing MD simulations in a quantitative fashion. They have been extensively used for peptide and protein folding, for small molecule binding, and for the study of native ensemble dynamics. Here, we adapt the MSM methodology to gain insight into the dynamics of misfolded states. To overcome possible flaws in root-mean-square deviation (RMSD) based metrics, we introduce a novel discretization approach, based on coarse grained contact maps. In addition, we extend the MSM methodology to include "sink" states in order to account for the irreversibility (on simulation time scales) of processes like protein misfolding. We apply this method to analyze the mechanism of misfolding of tandem repeats of titin domains, and how it is influenced by confinement in a chaperonin-like cavity. PMID- 26897002 TI - Gradient Distribution of Martensite Phase in Melt-Spun Ribbons of a Fe-Ni-Ti-Al Alloy. AB - Metallographic, X-ray diffraction and magnetometric analysis were used to study the regularities of martensitic transformation in melt-spun ribbons of a Fe - 28 wt. % Ni - 2.1 wt. % Ti - 2 wt. % Al - 0.05 wt. % C alloy. The substantial differences in volume fractions of the martensite phase in local regions of thin melt-spun ribbons of the alloy are related to the size effect of the transformation and structural inhomogeneity of the ribbons. The distribution of austenitic grain size in different local areas of melt-spun ribbons is significantly different. The principal factor for changing the completeness of the martensitic transformation is the size effect of transformation. Difference in the martensite volume fraction in local regions of a ribbon is mainly determined by the different volume fractions of ultrafine-grained (500-1000 nm) and nanosized (80-100 nm and less) initial austenite grains, in which the transformation was slowed down or completely suppressed. Other factors almost do not affect the completeness of the martensitic transformation. The strong stabilizing effect of the reverse alpha-gamma transformation with respect to the subsequent direct gamma-alpha transformation in the melt-spun ribbons is also related to the grain size effect. PMID- 26897003 TI - Developing a system that can automatically detect health changes using transfer times of older adults. AB - BACKGROUND: As gait speed and transfer times are considered to be an important measure of functional ability in older adults, several systems are currently being researched to measure this parameter in the home environment of older adults. The data resulting from these systems, however, still needs to be reviewed by healthcare workers which is a time-consuming process. METHODS: This paper presents a system that employs statistical process control techniques (SPC) to automatically detect both positive and negative trends in transfer times. Several SPC techniques, Tabular cumulative sum (CUSUM) chart, Standardized CUSUM and Exponentially Weighted Moving Average (EWMA) chart were evaluated. The best performing method was further optimized for the desired application. After this, it was validated on both simulated data and real-life data. RESULTS: The best performing method was the Exponentially Weighted Moving Average control chart with the use of rational subgroups and a reinitialization after three alarm days. The results from the simulated data showed that positive and negative trends are detected within 14 days after the start of the trend when a trend is 28 days long. When the transition period is shorter, the number of days before an alert is triggered also diminishes. If for instance an abrupt change is present in the transfer time an alert is triggered within two days after this change. On average, only one false alarm is triggered every five weeks. The results from the real-life dataset confirm those of the simulated dataset. CONCLUSIONS: The system presented in this paper is able to detect both positive and negative trends in the transfer times of older adults, therefore automatically triggering an alarm when changes in transfer times occur. These changes can be gradual as well as abrupt. PMID- 26897004 TI - Triple-barrelled aortic dissection with Stanford type A morphology. PMID- 26897005 TI - Diagnostic accuracy of sub-mSv prospective ECG-triggering cardiac CT in young infant with complex congenital heart disease. AB - To explore the clinical value and evaluate the diagnostic accuracy of sub-mSv low dose prospective ECG-triggering cardiac CT (CCT) in young infants with complex congenital heart disease (CHD). A total of 102 consecutive infant patients (53 boys and 49 girls with mean age of 2.9 +/- 2.4 m and weight less than 5 kg) with complex CHD were prospectively enrolled. Scans were performed on a 64-slice high definition CT scanner with low dose prospective ECG-triggering mode and reconstructed with 80 % adaptive statistical iterative reconstruction algorithm. All studies were performed during free breathing with sedation. The subjective image quality was evaluated by 5-point grading scale and interobserver variability was calculated. The objective image noise (standard deviation, SD) and contrast to noise ratio (CNR) was calculated. The effective radiation dose from the prospective ECG-triggering mode was recorded and compared with the virtual conventional retrospective ECG-gating mode. The detection rate for the origin of coronary artery was calculated. All patients also underwent echocardiography before CCT examination. 81 patients had surgery and their preoperative CCT and echocardiography findings were compared with the surgical results and sensitivity, specificity, positive and negative predictive values and accuracy were calculated for separate cardiovascular anomalies. Heart rates were 70-161 beats per minute (bpm) with mean value of 129.19 +/- 14.52 bpm. The effective dose of 0.53 +/- 0.15 mSv in the prospective ECG-triggering cardiac CT was lower than the calculated value in a conventional retrospective ECG-gating mode (2.00 +/- 0.35 mSv) (p < 0.001). The mean CNR and SD were 28.19 +/- 13.00 and 15.75 +/- 3.61HU, respectively. The image quality scores were 4.31 +/- 0.36 and 4.29 +/- 0.41 from reviewer 1 and 2 respectively with an excellent agreement between them (Kappa = 0.85). The detection rate for the origins of the left and right coronary arteries was 96 and 90 %, respectively. The detection rates of the origins of left coronary artery and right coronary artery in all cases were 96 % (78/81) and 90 % (73/81), respectively. Twenty cases of conotruncal anomalies and ALCAPA were validated surgically and the accuracy of cardiac CT diagnosis was 95 % (19/20). The overall deformity based sensitivity, specificity, positive predictive value and negative predictive value were 94.0.1, 99.9, 98.6, 99.5 % respectively, by CCT, and 88.2, 99.9, 97.8, 99.0 %, respectively, by echocardiography. Prospective ECG-triggering CCT with sub-mSv effective dose provides excellent imaging quality and high diagnostic accuracy for young infants with complex CHD. PMID- 26897006 TI - An urban approach to planetary boundaries. AB - The achievement of global sustainable development goals subject to planetary boundaries will mostly be determined by cities as they drive cultures, economies, material use, and waste generation. Locally relevant, applied and quantitative methodologies are critical to capture the complexity of urban infrastructure systems, global inter-connections, and to monitor local and global progress toward sustainability. An urban monitoring (and communications) tool is presented here illustrating that a city-based approach to sustainable development is possible. Following efforts to define and quantify safe planetary boundaries in areas such as climate change, biosphere integrity, and freshwater use, this paper modifies the methodology to propose boundaries from a city's perspective. Socio economic boundaries, or targets, largely derived from the Sustainable Development Goals are added to bio-physical boundaries. Issues such as data availability, city priorities, and ease of implementation are considered. The framework is trialed for Toronto, Shanghai, Sao Paulo, Mumbai, and Dakar, as well as aggregated for the world's larger cities. The methodology provides an important tool for cities to play a more fulsome and active role in global sustainable development. PMID- 26897007 TI - Getting past the blame game: Convergence and divergence in perceived threats to salmon resources among anglers and indigenous fishers in Canada's lower Fraser River. AB - This article examines threat perception as a potential dimension of inter-group conflict over salmon fisheries in Canada's Fraser River watershed. Environmental changes and the entry of new user groups are putting pressure on both the resource and regulators, as well as threatening to exacerbate conflicts, notably between First Nation (indigenous) fishers and non-indigenous recreational anglers. While resource conflicts are often superficially conceptualized as cases of competing interests, we build on recent studies suggesting that conflicts are associated with deeper cognitive and perceptual differences among user groups. We report findings from 422 riverbank interviews with First Nation fishers and recreational anglers focusing on perceptions of threat to the fisheries. Responses reveal both substantial agreement and disagreement in threat perceptions between the two groups. These patterns provide a potential roadmap for consensus building, and suggest possible avenues for policy-makers to defuse the "blame game" that often dominates this type of conflict. PMID- 26897009 TI - Evaluation of cytotoxic and tumor targeting capability of (177)Lu-DOTATATE nanoparticles: a trailblazing strategy in peptide receptor radionuclide therapy. AB - OBJECTIVE: We propose an innovative strategy of nanoparticle-mediated-peptide receptor radionuclide therapy (PRRT) employing PLGA-nanoparticles together with anti-beta-hCG antibodies that can protect kidneys from radiation damage while simultaneously enhancing its tumor targeting and cytotoxic ability for somatostatin receptor (SSR) positive tumors. METHODS: PEG-coated-(177)Lu-DOTATATE PLGA-nanoparticles (PEG-LuD-NP) were formulated and characterized. In vitro toxicity of these particles was tested on human glioblastoma cell line U87MG over a radiation dose range of 19-78 Gy, using MTT assay and flow cytometry. To further enhance cytotoxicity and test the feasibility of active tumor targeting, apoptosis-inducing anti-beta-hCG monoclonal antibodies were employed in vitro, after confirming expression of beta-hCG on U87MG. In vivo tumor targeting ability of these particles, in comparison to uncoated particles and un-encapsulated (177)Lu-DOTATATE, was assessed by intravenous administration in tumor-induced wistar rats. Rats were first imaged in a gamma camera followed by euthanasia for organ extraction and counting in gamma counter. RESULTS: The particles were spherical in shape with mean diameter of 300 nm. Highest cytotoxicity that could be achieved with PEG-LuD-NP, on radio-resistant U87MG cells, was 35.8 % due to complex cellular response triggered by ionizing radiation. Interestingly, synergistic action of antibodies and PEG-LuD-NP doubled the cytotoxicity (80 %). PEG-LuD-NP showed the highest tumor uptake (4.3 +/- 0.46 % ID/g) as compared to (177)Lu-DOTATATE (3.5 +/- 0.31 %) and uncoated-(177)Lu-DOTATATE-nanoparticles (3.4 +/- 0.35 %) in tumor-inoculated wistar rats (p < 0.001). Renal uptake/retention was decreased 3-4 folds with these particles, resulting in the highest tumor-to-kidney ratio (8.58; p < 0.01) while tumor-to-liver and tumor-to bone ratios were comparable to un-encapsulated-drug. CONCLUSION: Nanocarrier mediated-PRRT is an effective way of targeting SSR positive tumors for enhanced cytoxicity and reduced renal radiation dose associated with conventional PRRT. To our knowledge of literature, this is the first study to establish in vitro and in vivo efficacy profile of nanoparticles in PRRT providing a stepping-stone for undergoing and future research endeavors in the direction of abating associated radiation concerns of radionuclide therapy and may offer a paradigm shift in PRRT strategy. PMID- 26897008 TI - Normal values and standardization of parameters in nuclear cardiology: Japanese Society of Nuclear Medicine working group database. AB - As a 2-year project of the Japanese Society of Nuclear Medicine working group activity, normal myocardial imaging databases were accumulated and summarized. Stress-rest with gated and non-gated image sets were accumulated for myocardial perfusion imaging and could be used for perfusion defect scoring and normal left ventricular (LV) function analysis. For single-photon emission computed tomography (SPECT) with multi-focal collimator design, databases of supine and prone positions and computed tomography (CT)-based attenuation correction were created. The CT-based correction provided similar perfusion patterns between genders. In phase analysis of gated myocardial perfusion SPECT, a new approach for analyzing dyssynchrony, normal ranges of parameters for phase bandwidth, standard deviation and entropy were determined in four software programs. Although the results were not interchangeable, dependency on gender, ejection fraction and volumes were common characteristics of these parameters. Standardization of (123)I-MIBG sympathetic imaging was performed regarding heart to-mediastinum ratio (HMR) using a calibration phantom method. The HMRs from any collimator types could be converted to the value with medium-energy comparable collimators. Appropriate quantification based on common normal databases and standard technology could play a pivotal role for clinical practice and researches. PMID- 26897010 TI - Diagnostic value of metabolic heterogeneity as a reliable parameter for differentiating malignant parotid gland tumors. AB - OBJECTIVE: Exact classifying between malignant and benign tumors in the parotid gland is important because the cancer has relatively poor prognosis. There have been several studies that F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) can differentiate between malignant and benign parotid gland tumors. However, the role of FDG PET is still controversial because many benign parotid gland tumors, such as Warthin's tumor and pleomorphic adenoma, show high FDG uptake. We hypothesized that metabolic heterogeneity would differentiate malignant parotid tumors because tumoral heterogeneity is an important characteristic in the malignancies. METHODS: From January 2010 to April 2015, we retrospectively reviewed the 46 patients who showed FDG uptake at the parotid gland. To differentiate malignant parotid gland tumors, we obtained maximum SUV and mean SUV. Metabolic tumor volume and total lesion glycolysis were measured as metabolic volumetric parameters. We also included heterogeneity parameters of FDG PET such as heterogeneity factor (HF) and the coefficient of variation for all patients. RESULTS: There was significant difference of HF between malignant ( 0.30 +/- 0.25; range -0.937 to -0.084) and benign parotid gland tumors (-0.06 +/- 0.05; range -0.291 to -0.012; p < 0.0001). In receiver operating characteristic analysis, when <=-0.084 was used as the cut-off value for HF, the sensitivity and specificity were 100 % (95 % CI 81.5-100) and 89.2 % (95 % CI 71.8-97.7), respectively. HF showed the highest area under the curve of 0.947 among the parameters. In logistic regression analysis, the HF was the most powerful factor for differentiation of the parotid gland tumors (p = 0.002). CONCLUSIONS: Our results suggest that HF can be utilized as a reliable and non-invasive method for differentiation of malignant and benign parotid gland tumors. PMID- 26897011 TI - Erratum to: A flow cytometry-based reporter assay identifies macrolide antibiotics as nonsense mutation read-through agents. PMID- 26897012 TI - Combining traditional anatomy lectures with e-learning activities: how do students perceive their learning experience? AB - OBJECTIVE: The purpose of this study was to investigate how students perceived their learning experience when combining traditional anatomy lectures with preparatory e-learning activities that consisted of fill-in-the-blank assignments, videos, and multiple-choice quizzes. METHODS: A qualitative study was conducted to explore changes in study behaviour and perception of learning. Three group interviews with students were conducted and thematically analysed. RESULTS: Data was categorized into four themes: 1. Approaching the course material, 2. Understanding the material, 3. Consolidating the material, and 4. Perceived learning outcome. Students appreciated the clear structure of the course, and reported that online activities encouraged them towards a first engagement with the material. They felt that they were more active during in class sessions, described self-study before the end-of-term exam as easier, and believed that contents would remain in their memories for a longer time. CONCLUSIONS: By adjusting already existing resources, lectures can be combined fairly easily and cost-effectively with preparatory e-learning activities. The creation of online components promote well-structured courses, can help minimize 'student passivity' as a characteristic element of lectures, and can support students in distributing their studies throughout the term, thus suggesting enhanced learning. Further research work should be designed to confirm the afore mentioned findings through objective measurements of student learning outcomes. PMID- 26897013 TI - Positron emission tomography of high-grade gliomas. AB - High-grade gliomas [HGG (WHO grades III-IV)] are almost invariably fatal. Imaging of HGG is important for orientating diagnosis, prognosis and treatment planning and is crucial for development of novel, more effective therapies. Given the potentially unlimited number of usable tracing molecules and the elevated number of available radionuclides, PET allows gathering multiple informations on HGG including data on tissue metabolism and drug pharmacokinetics. PET studies on the diagnosis, prognosis and treatment of HGG carried out by most frequently used tracers and radionuclides ((11)C and (18)F) and published in 2014 have been reviewed. These studies demonstrate that a thorough choice of tracers may confer elevated diagnostic and prognostic power to PET imaging of HGG. They also suggest that a combination of PET and MRI may give the most complete and reliable imaging information on HGG and that research on hybrid PET/MRI may be paying back in terms of improved diagnosis, prognosis and treatment planning of these deadly tumours. PMID- 26897014 TI - Neuro-oncology biotech industry progress report. AB - The Brain Tumor Biotech Center at the Feinstein Institute for Medical Research, in collaboration with Voices Against Brain Cancer hosted The Brain Tumor Biotech Summit at in New York City in June 2015. The focus was once again on fostering collaboration between neuro-oncologist, neurosurgeons, scientists, leaders from biotechnology and pharmaceutical industries, and members of the financial community. The summit highlighted the recent advances in the treatment of brain tumor, and specifically focused on targeting of stem cells and EGFR, use of prophage and immunostimulatory vaccines, retroviral vectors for drug delivery, biologic prodrug, Cesium brachytherapy, and use of electric field to disrupt tumor cell proliferation. This article summarizes the current progress in brain tumor research as presented at 2015 The Brain Tumor Biotech Summit. PMID- 26897015 TI - Clinical features of subarachnoid hemorrhage in patients with positive cancer history. AB - Advances in cancer treatment have dramatically increased long-term survivors. Prolonged survival increases comorbidity risk, but there is a paucity of studies on how cancer history alters clinical outcomes from subsequent diseases. This study aims to investigate whether positive cancer history influences clinical outcome following subarachnoid hemorrhage (SAH). We retrospectively reviewed consecutive SAH patients admitted between January 2008 and March 2014. Medical histories, known SAH risk factors, and outcome were compared between SAH patients with and without cancer history. Out of the 498 SAH patients, 55 cases had cancer history, 438 cases had no cancer history and 5 cases had an unknown cancer history. Compared with SAH patients without cancer history, those with cancer history had poorer Hunt & Hess grade at SAH presentation (P = 0.021), and poorer modified Rankin Scale (mRS) score at discharge (P < 0.001). After adjustment for age, sex, modified Fisher, previous SAH, history of hypertension, current smoking status, and current alcohol consumption, positive cancer history remained an independent risk factor for poorer mRS0-6 [odds ratio (OR) = 2.25, 95 % confidence interval (CI) 1.28-3.94] and mRS6 (OR = 2.74, 95 % CI 1.40-5.37). Furthermore, stratified analysis by Hunt & Hess grade adjusted by age, sex, and modified Fisher scale, OR of poorer mRS0-6 was 2.12 (95 % CI 0.89-5.05) and OR of mRS6 was 3.68 (95 % CI 1.35-10.04). After adjustment of patients for demographic factors, classical risk factors for SAH and Hunt & Hess grade, previous cancer history is a risk factor for the poor functional outcome of SAH. PMID- 26897017 TI - Dose effects of lacosamide as add-on therapy for partial-onset seizure in adult. AB - The objective of the study was to evaluate the dose effects of lacosamide on the efficacy and safety as adjunctive therapy for partial-onset seizure in adults. We searched online databases such as Pubmed, Embase, Cochrane Online Library, and Clinicaltrial.gov for randomized control trials. A meta-analysis was performed on RevMan 5.3 software. Four randomized control trials with 1855 patients out of 310 citations and 30 registered trials were identified. 400 mg/d was more effective than 200 mg/d [RR 1.23 (95 % CI 1.05-1.45), P = 0.01], but the 600 mg/d didn't show more benefit than 400 mg/d [RR 1.01 (95 % CI 0.81-1.27), P = 0.90]. Increasing the dosage led to higher incidence of quitting the medication because of adverse events [400 vs. 200 mg/d RR 2.17 (95 % CI 1.15-4.11), P = 0.02; 600 vs. 400 mg/d RR 1.55 (95 % CI 1.12-2.15), P = 0.009]. Incidence of serious adverse events did not occur with the increase of dose [400 vs. 200 mg/d RR 1.26 (95 % CI 0.50-3.20), P = 0.62], [600 vs. 400 mg/d RR 0.52 (95 % CI 0.21-1.30), P = 0.16]. A dose of 400 mg/d resulted in a higher chance of dizziness [RR 1.50 (95 % CI 1.02-2.20), P = 0.04], vomiting [RR 1.73 (95 % CI 1.03-2.90), P = 0.04], and diplopia [RR 1.98 (95 % CI 1.19-3.30), P = 0.008] than that of 200 mg/d. 400 mg/d is the optimal dose for efficacy. The dose of 200 mg/d has the best safety for less occurrence of adverse events and less quitting. Current evidence suggests that a dose of 600 mg/d is unnecessary, except for particular reasons. PMID- 26897016 TI - Auditory functional magnetic resonance imaging in dogs--normalization and group analysis and the processing of pitch in the canine auditory pathways. AB - BACKGROUND: Functional magnetic resonance imaging (fMRI) is an advanced and frequently used technique for studying brain functions in humans and increasingly so in animals. A key element of analyzing fMRI data is group analysis, for which valid spatial normalization is a prerequisite. In the current study we applied normalization and group analysis to a dataset from an auditory functional MRI experiment in anesthetized beagles. The stimulation paradigm used in the experiment was composed of simple Gaussian noise and regular interval sounds (RIS), which included a periodicity pitch as an additional sound feature. The results from the performed group analysis were compared with those from single animal analysis. In addition to this, the data were examined for brain regions showing an increased activation associated with the perception of pitch. RESULTS: With the group analysis, significant activations matching the position of the right superior olivary nucleus, lateral lemniscus and internal capsule were identified, which could not be detected in the single animal analysis. In addition, a large cluster of activated voxels in the auditory cortex was found. The contrast of the RIS condition (including pitch) with Gaussian noise (no pitch) showed a significant effect in a region matching the location of the left medial geniculate nucleus. CONCLUSION: By using group analysis additional activated areas along the canine auditory pathways could be identified in comparison to single animal analysis. It was possible to demonstrate a pitch specific effect, indicating that group analysis is a suitable method for improving the results of auditory fMRI studies in dogs and extending our knowledge of canine neuroanatomy. PMID- 26897020 TI - Erratum to: Prescribing pattern and resource utilization of monoamine oxidase-B inhibitors in Parkinson treatment: comparison between rasagiline and selegiline. PMID- 26897019 TI - The Italian stroke-app: ICTUS3R. AB - Any strategy to reduce stroke burden involves crucial inputs from individuals (risk reduction, rapid recognition and response to symptoms onset) which imply a certain level of stroke knowledge. Health-related applications (apps) have been identified as a novel platform for dissemination of health information to the public. Only few apps about stroke are currently available with scientifically valid information, none of them are available in Italian. We developed the first and only Italian stroke app, ICTUS3R. We also pilot tested ICTUS3R in terms of its usage during the first 12 months following release (October 30, 2014). ICTUS3R was developed in collaboration with communication experts, stroke leaders and web producers. ICTUS3R was pilot tested in terms of number and distribution of downloads. Data about 1 year usage were anonymously collected from ICTUS 3R release on October 30, 2014. ICTUS3R includes a stroke screening tool, information how to react in case of suspected stroke, and information about risk factors including personal stroke risk calculator. ICTUS 3R web site was visited 36,242 times. Mean session duration was over 2 min. The 48 % of downloads were by individuals aged 25-44 years, 12 % by individuals >=55 years. ICTUS3R downloads were distributed across all the Italian provinces, in varying proportions. The 4.3 % of downloads were done outside Italy. ICTUS3R can be an important contribution to stroke management and prevention, it proved to be well received for dissemination of stroke information among Italians. Its use could contribute to reduce stroke burden in Italy. PMID- 26897018 TI - Interleukin-18 -137 G/C and -607 C/A polymorphisms and Alzheimer's disease risk: a meta-analysis. AB - The -137 G/C and -607 C/A polymorphisms in interleukin-18 (IL-18) gene have been reported to be associated with Alzheimer's disease (AD) risk, but the results are inconclusive. Considering a single study may lack the power to provide reliable conclusion, we performed a meta-analysis to investigate the association between the IL-18 -137 G/C and -607 C/A polymorphisms and AD susceptibility. A comprehensive literature search of PubMed, Embase, China National Knowledge Infrastructure (CNKI) and Wanfang databases were conducted before September 1, 2015. The pooled odds ratio (OR) with 95 % confidence intervals (CIs) were calculated. Five eligible studies with a total of 1536 subjects were finally included in this meta-analysis. For the IL-18 -137 G/C polymorphism, a significantly decreased risk was detected in patients carrying the C allele of 137 G/C in all study subjects in allele model (C vs. G: OR = 0.816, 95 % CI = 0.680-0.980, p = 0.029). Moreover, stratification by ethnicity indicated markedly association between the -137 G/C C allele and AD risk in Asians. For the IL-18 607 C/A polymorphism, a significantly decreased risk was found in patients carrying the A allele of -607 C/A in all study subjects in dominant model (AA + CA vs. CC: OR = 0.696, 95 % CI = 0.529-0.915, p = 0.010). However, the results suggested no significant association between the -607 C/A polymorphism and AD susceptibility when stratified by ethnicity. Our present meta-analysis suggests that the C allele carrier of IL-18 -137 G/C was associated with decreased risk for AD in Asians. Further well-designed case-control studies with larger sample size and more ethnic groups are needed to confirm these conclusions. PMID- 26897021 TI - Epidemiology of toxoplasmosis: role of the tick Haemaphysalis longicornis. AB - BACKGROUND: Toxoplasma gondii infection is mainly caused by ingestion of water or food that is contaminated with oocysts excreted by cats, or by eating raw meat containing T. gondii tissue cysts. However, oral transmission does not explain the common occurrence of toxoplasmosis in a variety of hosts, such as herbivorous animals, birds, and wild rodents. Little information exists on the maintenance of T. gondii parasites in nature and routes of transmission to domestic and wild animal hosts. Therefore, this study evaluated the role of Haemaphysalis longicornis ticks in the epidemiology of toxoplasmosis. METHODS: The real-time polymerase chain reaction (qPCR) technique was used to detect the presence of T. gondii DNA in ticks collected from the field. To observe the amount of dynamic changes of T. gondii in the tick's body and its infectivity, microinjection of green fluorescence parasites was performed. Under laboratory conditions, we evaluated if H. longicornis ticks were infected with T. gondii and their potential to transmit the infection to other hosts using traditional parasitological methods coupled with molecular detection techniques. RESULTS: The infection rates of T. gondii parasites among field-collected adult and nymph H. longicornis ticks were 11.26 % and 5.95 %, respectively. T. gondii can survive and remain infective in a tick's body for at least 15 days. We found that blood feeding of infected ticks did not transmit T. gondii to hosts, however, ingestion of infected ticks may be a transmission route between ticks and other common hosts. CONCLUSION: The T. gondii infection in ticks could serve as a reservoir for toxoplasmosis transmission. PMID- 26897023 TI - Bariatric surgery implementation trends in the USA from 2002 to 2012. AB - BACKGROUND: Many beneficial health care interventions are either not put into practice or fail to diffuse over time due to complex contextual factors that affect implementation and diffusion. Bariatric surgery is an example of an effective intervention that recently experienced a plateau and decrease in rates, with minimal documented justification for this trend. While there are conceptual models that provide frameworks of general innovation implementation and diffusion, few studies have tested these models with data to measure the relative effects of factors that affect diffusion of specific health care interventions. METHODS: A literature review identified factors associated with implementation and diffusion of health care innovations. These factors were utilized to construct a conceptual model of diffusion to explain changes in bariatric surgery over time. Six data sources were used to construct measures of the study population and factors in the model that may affect diffusion of surgery. The population included obese and morbidly obese patients from 2002 to 2012 who had bariatric surgery in 15 states. Multivariable models were used to identify environmental, population, and medical practice factors that facilitated or impeded diffusion of bariatric surgery over time. RESULTS: It was found that while bariatric surgery rates increased over time, the speed of growth in surgeries, or diffusion, slowed. Higher cumulative number of surgeries and higher proportion of the state population in age group 50-59 slowed surgery growth, but presence of Medicare centers of excellence increased the speed of surgery diffusion. Over time, the factors affecting the diffusion of bariatric surgery fluctuated, indicating that diffusion is affected by temporal and cumulative effects. CONCLUSIONS: The primary driver of diffusion of bariatric surgery was the extent of centers of excellence presence in a state. Higher cumulative surgery rates and higher proportions of older populations in a state slowed diffusion. Surprisingly, measures of the presence of champions were not significant, perhaps because these are difficult to measure in the aggregate. Our results generally support the conceptual model of diffusion developed from the literature, which may be useful for examining other innovations, as well as for designing interventions to support rapid diffusion of innovations to improve health outcomes and quality of care. PMID- 26897022 TI - Ligation of RNA Oligomers by the Schistosoma mansoni Hammerhead Ribozyme in Frozen Solution. AB - The interstitial liquid phase within frozen aqueous solutions is an environment that minimizes RNA degradation and facilitates reactions that may have relevance to the RNA World hypothesis. Previous work has shown that frozen solutions support condensation of activated nucleotides into RNA oligomers, RNA ligation by the hairpin ribozyme, and RNA synthesis by a RNA polymerase ribozyme. In the current study, we examined the activity of a hammerhead ribozyme (HHR) in frozen solution. The Schistosoma mansoni hammerhead ribozyme, which predominantly cleaves RNA, can ligate its cleaved products (P1 and P2) with yields up to ~23 % in single turnover experiments at 25 degrees C in the presence of Mg(2+). Our studies show that this HHR ligates RNA oligomers in frozen solution in the absence of divalent cations. Citrate and other anions that exhibit strong ion water affinity enhanced ligation. Yields up to 43 % were observed in one freeze thaw cycle and a maximum of 60 % was obtained after several freeze-thaw cycles using wild-type P1 and P2. Truncated and mutated P1 substrates were ligated to P2 with yields of 14-24 % in one freeze-thaw cycle. A pool of P2 substrates with mixtures of all four bases at five positions were ligated with P1 in frozen solution. High-throughput sequencing indicated that 70 of the 1024 possible P2 sequences were represented in ligated products at 1000 or more read counts per million reads. The results indicate that the HHR can ligate a range of short RNA oligomers into an ensemble of diverse sequences in ice. PMID- 26897024 TI - Clinical management of pineal cysts: a worldwide online survey. AB - BACKGROUND: A pineal cyst is a benign affection of a pineal gland on the borderline between a pathological lesion and a variant of normality. Clinical management of patients with a pineal cyst remains controversial, especially when patients present with non-specific symptoms. METHODS: An online questionnaire consisting of 13 questions was completed by 110 neurosurgeons worldwide. Responses were entered into a database and subsequently analysed. RESULTS: Based on data from the questionnaire, the main indication criteria for pineal cyst resection are hydrocephalus (90 % of the respondents), Parinaud's syndrome (80 %) and growth of the cyst (68 %). Only 15 % of the respondents occasionally operate on patients with non-specific symptoms. If surgery is indicated, improvement is expected in 88 % of the patients. The vast majority of the respondents favour a supracerebellar infratentorial approach to the pineal region. Most (78 %) of the respondents regarded the patient registry as a potentially useful instrument. CONCLUSIONS: This survey sheds light on the current practice of pineal cyst management across the world. Most of the respondents perform surgery on pineal cysts only if patients are presenting with symptoms attributable to a mass effect. Surgery for patients with non-specific complaints (headache, vertigo) is not widely accepted, although it may prove effective. A prospective patient registry might be useful in the decision-making process in the clinical management of pineal cysts. PMID- 26897025 TI - Rasip1 is essential to blood vessel stability and angiogenic blood vessel growth. AB - Cardiovascular function depends on patent, continuous and stable blood vessel formation by endothelial cells (ECs). Blood vessel development initiates by vasculogenesis, as ECs coalesce into linear aggregates and organize to form central lumens that allow blood flow. Molecular mechanisms underlying in vivo vascular 'tubulogenesis' are only beginning to be unraveled. We previously showed that the GTPase-interacting protein called Rasip1 is required for the formation of continuous vascular lumens in the early embryo. Rasip1(-/-) ECs exhibit loss of proper cell polarity and cell shape, disrupted localization of EC-EC junctions and defects in adhesion of ECs to extracellular matrix. In vitro studies showed that Rasip1 depletion in cultured ECs blocked tubulogenesis. Whether Rasip1 is required in blood vessels after their initial formation remained unclear. Here, we show that Rasip1 is essential for vessel formation and maintenance in the embryo, but not in quiescent adult vessels. Rasip1 is also required for angiogenesis in three models of blood vessel growth: in vitro matrix invasion, retinal blood vessel growth and directed in vivo angiogenesis assays. Rasip1 is thus necessary in growing embryonic blood vessels, postnatal angiogenic sprouting and remodeling, but is dispensable for maintenance of established blood vessels, making it a potential anti-angiogenic therapeutic target. PMID- 26897026 TI - Current Treatments of Bruxism. AB - OPINION STATEMENT: Despite numerous case reports, the evidence for treatment of bruxism is still low. Different treatment modalities (behavioral techniques, intraoral devices, medications, and contingent electrical stimulation) have been applied. A clinical evaluation is needed to differentiate between awake bruxism and sleep bruxism and rule out any medical disorder or medication that could be behind its appearance (secondary bruxism). A polysomnography is required only in a few cases of sleep bruxism, mostly when sleep comorbidities are present. Counselling with regard to sleep hygiene, sleep habit modification, and relaxation techniques has been suggested as the first step in the therapeutic intervention, and is generally considered not harmful, despite low evidence of any efficacy. Occlusal splints are successful in the prevention of dental damage and grinding sounds associated with sleep bruxism, but their effects on reducing bruxism electromyographic (EMG) events are transient. In patients with psychiatric and sleep comorbidities, the acute use of clonazepam at night has been reported to improve sleep bruxism, but in the absence of double-blind randomized trials, its use in general clinical practice cannot be recommended. Severe secondary bruxism interfering with speaking, chewing, or swallowing has been reported in patients with neurological disorders such as in cranial dystonia; in these patients, injections of botulinum toxin in the masticatory muscles may decrease bruxism for up to 1-5 months and improve pain and mandibular functions. Long-term studies in larger and better specified samples of patients with bruxism, comparing the effects of different therapeutic modalities on bruxism EMG activity, progression of dental wear, and orofacial pain are current gaps of knowledge and preclude the development of severity-based treatment guidelines. PMID- 26897027 TI - Molecular foundations of chilling-tolerance of modern maize. AB - BACKGROUND: Recent progress in selective breeding of maize (Zea mays L.) towards adaptation to temperate climate has allowed the production of inbred lines withstanding cold springs with temperatures below 8 degrees C or even close to 0 degrees C, indicating that despite its tropical origins maize is not inherently cold-sensitive. RESULTS: Here we studied the acclimatory response of three maize inbred lines of contrasting cold-sensitivity selected basing on multi-year routine field data. The field observations were confirmed in the growth chamber. Under controlled conditions the damage to the photosynthetic apparatus due to severe cold treatment was the least in the cold-tolerant line provided that it had been subjected to prior moderate chilling, i.e., acclimation. The cold sensitive lines performed equally poorly with or without acclimation. To uncover the molecular basis of the attained cold-acclimatability we performed comparative transcriptome profiling of the response of the lines to the cold during acclimation phase by means of microarrays with a statistical and bioinformatic data analysis. CONCLUSIONS: The analyses indicated three mechanisms likely responsible for the cold-tolerance: acclimation-dependent modification of the photosynthetic apparatus, cell wall properties, and developmental processes. Those conclusions supported the observed acclimation of photosynthesis to severe cold at moderate chilling and were further confirmed by experimentally showing specific modification of cell wall properties and repression of selected miRNA species, general regulators of development, in the cold-tolerant line subjected to cold stress. PMID- 26897028 TI - Structural and Functional Insights on an Uncharacterized Agamma-Globin-Gene Polymorphism Present in Four beta0-Thalassemia Families with High Fetal Hemoglobin Levels. AB - INTRODUCTION: Several DNA polymorphisms have been associated with high production of fetal hemoglobin (HbF), although the molecular basis is not completely understood. In order to identify and characterize novel HbF-associated elements, we focused on five probands and their four families (from Egypt, Iraq and Iran) with thalassemia major (either beta(0)-IVSII-1 or beta(0)-IVSI-1) and unusual HbF elevation (>98 %), congenital or acquired after rejection of bone marrow transplantation, suggesting an anticipated favorable genetic background to high HbF expression. METHODS: Patient recruitment, genomic DNA sequencing, western blotting, electrophoretic mobility shift assays, surface plasmon resonance (SPR) biospecific interaction analysis, bioinformatics analyses based on docking experiments. RESULTS: A polymorphism of the Agamma-globin gene is here studied in four families with beta(0)-thalassemia (beta(0)-IVSII-1 and beta(0)-IVSI-1) and expressing unusual high HbF levels, congenital or acquired after rejection of bone marrow transplantation. This (G->A) polymorphism is present at position +25 of the Agamma-globin genes, corresponding to a 5'-UTR region of the Agamma-globin mRNA and, when present, is physically linked in chromosomes 11 of all the familiar members studied to the XmnI polymorphism and to the beta(0)-thalassemia mutations. The region corresponding to the +25(G->A) polymorphism of the Agamma globin gene belongs to a sequence recognized by DNA-binding protein complexes, including LYAR (Ly-1 antibody reactive clone), a zinc-finger transcription factor previously proposed to be involved in down-regulation of the expression of gamma globin genes in erythroid cells. CONCLUSION: We found a novel polymorphism of the Agamma-globin gene in four families with beta(0)-thalassemia and high levels of HbF expression. Additionally, we report evidence suggesting that the Agamma globin gene +25(G->A) polymorphism decreases the efficiency of the interaction between this sequence and specific DNA binding protein complexes. PMID- 26897029 TI - The BBaRTS Healthy Teeth Behaviour Change Programme for preventing dental caries in primary school children: study protocol for a cluster randomised controlled trial. AB - BACKGROUND: Oral health behaviours such as establishing twice-daily toothbrushing and sugar control intake need parental self-efficacy (PSE) to prevent the development of childhood dental caries. A previous study has shown that behaviour change techniques (BCTs) delivered via a storybook can improve parental self efficacy to undertake twice-daily toothbrushing. OBJECTIVE: to determine whether an intervention (BBaRTS, Bedtime Brush and Read Together to Sleep), designed to increase PSE; delivered through storybooks with embedded BCTs, parenting skills and oral health messages, can improve child oral health compared to (1) an exactly similar intervention containing no behaviour change techniques, and (2) the BBaRTS intervention supplemented with home supply of fluoride toothpaste and supervised toothbrushing on schooldays. METHODS/DESIGN: A 2-year, three-arm, multicentre, cluster randomised controlled trial. PARTICIPANTS: children (estimated 2000-2600) aged 5-7 years and their families from 60 UK primary schools. INTERVENTION: Test group 1: a series of eight children's storybooks developed by a psychologist, public health dentist, science educator, children's author and illustrators, with guidance from the Department for Education (England). The books feature animal characters and contain embedded dental health messages, parenting skills and BCTs to promote good oral health routines focused on controlling sugar intake and toothbrushing, as well as reading at bedtime. Books are given out over 2 years. Test group 2: as Test group 1 plus home supplies of fluoride toothpaste (1000 ppmF), and daily supervised toothbrushing in school on schooldays. Active Control group: series of eight books with exactly the same stories, characters and illustrations, but without BCTs, dental health messages or parenting skills. Annual child dental examinations and parental questionnaires will be undertaken. A sub-set of participants will be invited to join an embedded study of the child's diet and salivary microbiota composition. PRIMARY OUTCOME MEASURE: dental caries experience in permanent teeth at age 7-8 years. DISCUSSION: A multi-disciplinary team was established to develop the BBaRTS Children's Healthy Teeth Programme. The books were developed in partnership with the Department for Education (England), informed by a series of focus groups with children, teachers and parents. TRIAL REGISTRATION: ISRCTN21461006 (date of registration 23 September 2015). PMID- 26897030 TI - Wenyang Huazhuo Tongluo formula, a Chinese herbal decoction, improves skin fibrosis by promoting apoptosis and inhibiting proliferation through down regulation of survivin and cyclin D1 in systemic sclerosis. AB - BACKGROUND: Fibrosis is a major contributor to systemic sclerosis (SSc)-related morbidity, and rapid, progressive skin involvement predicts later mortality. Western medicine therapies for SSc cannot produce satisfactory effects currently, while Traditional Chinese Medicine (TCM), such as the Wenyang Huazhuo Tongluo (WYHZTL) formula, a Chinese herbal decoction, has shown amazing anti-fibrosis efficacy on SSc in clinical applications. This study is aiming to investigate the anti-fibrotic mechanism of WYHZTL formula for the treatment of SSc. METHODS: Fibroblasts from primary culture of skin lesions of SSc patients were exposed to rat medicated sera containing WYHZTL or XAV939, a small-molecule inhibitor of both tankyrase 1/2 and Wnt/beta-catenin pathway. Cell counting kit-8 assay and Annexin V FITC/PI apoptosis kit were used to analyze cell proliferation and apoptosis in fibroblasts, respectively. Reverse transcription-polymerase chain reaction (RT-PCR) and western blotting were used to detect the mRNA and protein levels of cyclin D1 and survivin. RESULTS: After 28, 48 and 72 h of incubation, the proliferative ability of the fibroblasts cells was obviously reduced by the sera containing WYHZTL compared with that in the control group; the percentage of apoptotic cell population in the sera containing WYHZTL treated fibroblasts cells was significantly higher than that in those treated with the control sera, and was about similar to that in those treated with XAV939. The sera containing WYHZTL could down-regulate both mRNA and protein levels of cyclin D1 and survivin, compared with the control group. CONCLUSIONS: The present study demonstrates the antiproliferative and pro-apoptotic actions of WYHZTL formula against fibroblasts and the effect may be related to the down-regulation of mRNA and protein levels of cyclin D1 and survivin in SSc. PMID- 26897032 TI - Journal of Clinical Monitoring and Computing 2015 end of year summary: tissue oxygenation and microcirculation. AB - Last year we started this series of end of year summaries of papers published in the 2014 issues of the Journal Of Clinical Monitoring And Computing with a review on near infrared spectroscopy (Scheeren et al. in J Clin Monit Comput 29(2):217 220, 2015). This year we will broaden the scope and include papers published in the field of tissue oxygenation and microcirculation, or a combination of both entities. We present some promising new technologies that might enable a deeper insight into the (patho)physiology of certain diseases such as sepsis, but also in healthy volunteers. These may help researchers and clinicians to evaluate both tissue oxygenation and microcirculation beyond macro-hemodynamic measurements usually available at the bedside. PMID- 26897031 TI - Effectiveness of Tachosil((r)) in the prevention of postoperative pancreatic fistula after distal pancreatectomy: a systematic review and meta-analysis. AB - PURPOSE: Postoperative pancreatic fistula (POPF) is a frequent and clinically relevant problem after distal pancreatectomy. A variety of methods have been tested in the attempt to prevent POPF, most of them without convincing results. METHODS: A systematic literature search was conducted in PubMed, Embase and the Cochrane Library to identify clinical studies comparing pancreatic stump closure with the addition of Tachosil((r)) to conventional stump closure. The identified studies were critically appraised, and meta-analyses were performed using a random-effects model. Dichotomous data were pooled using odds ratios, and weighted mean differences were calculated for continuous outcomes, together with the corresponding 95 % confidence intervals. RESULTS: Four studies (two randomised controlled trials and two retrospective clinical studies) reporting data from 738 patients were included in the meta-analysis. Overall POPF, clinically-relevant POPF, mortality, reoperations, intraoperative blood loss and length of hospital stay did not differ significantly between conventional closure and additional covering of the pancreatic stump with Tachosil((r)). A sensitivity analysis of only randomised controlled trials confirmed the results. CONCLUSIONS: The application of Tachosil((r)) to the pancreatic stump after distal pancreatectomy is a safe procedure but provides no relevant benefit in terms of POPF, mortality, reoperation rate, blood loss or length of hospital stay. Future research should concentrate on novel methods of pancreatic stump closure to prevent POPF after distal pancreatectomy. PMID- 26897033 TI - Hypoxic events and concomitant factors in preterm infants on non-invasive ventilation. AB - Automated control of inspired oxygen for newborn infants is an emerging technology, currently limited by reliance on a single input signal (oxygen saturation, SpO2). This is while other signals that may herald the onset of hypoxic events or identify spurious hypoxia are not usually utilised. We wished to assess the frequency of apnoea, loss of circuit pressure and/or motion artefact in proximity to hypoxic events in preterm infants on non-invasive ventilation. Hypoxic events (SpO2 < 80 %) were identified using a previously acquired dataset obtained from preterm infants receiving non-invasive ventilation. Events with concomitant apnoea, loss of circuit pressure or oximetry motion artefact were annotated, and the frequency of each of these factors was determined. The effect of duration and timing of apnoea on the characteristics of the associated hypoxic events was studied. Among 1224 hypoxic events, 555 (45 %) were accompanied by apnoea, 31 (2.5 %) by loss of circuit pressure and 696 (57 %) by motion artefact, while for 224 (18 %) there were no concomitant factors identified. Respiratory pauses of longer duration (>15 s) preceding hypoxic events, were associated with a relatively slow decline in SpO2 and more prolonged hypoxia compared to shorter pauses. Hypoxic events are frequently accompanied by respiratory pauses and/or motion artefact. Real-time monitoring and input of respiratory waveform may thus improve the function of automated oxygen controllers, allowing pre-emptive responses to respiratory pauses. Furthermore, use of motion-resistant oximeters and plethysmographic waveform assessment procedures will help to optimise feedback control of inspired oxygen delivery. PMID- 26897034 TI - Practice patterns in the intraoperative use of bispectral index monitoring. AB - Assessing the depth of anesthesia and reducing intraoperative awareness has become a focus of much technology development and research in the field of anesthesia. Bispectral index (BIS) is the most widely utilized technology that uses electroencephalogram to provide a measurement of anesthetic depth. There are no definitive guidelines on when BIS should be used. Our aim was to assess actual patterns of intraoperative use of BIS by anesthesia professionals. We retrospectively collected intraoperative data on 55,210 surgical cases at a tertiary care hospital. Variables collected included: age, sex, body mass index (BMI), American Society of Anesthesiologists (ASA) physical status, anesthesia provider type and level of training, use of inhalational anesthetics versus total intravenous anesthesia (TIVA), utilization of nitrous oxide, utilization of non depolarizing neuromuscular blockade, emergency status of surgery, airway type, case duration, and surgical subspecialty. A univariate logistic regression model was fitted. Subsequently, a multivariate logistic regression model was applied. Covariates utilized for the model included age, anesthesia provider level, and length of case. Factors associated with BIS use included increased age, greater ASA physical status, extremes of BMI, use of TIVA, use of a long-acting paralytic agent, use of an endotracheal tube (ETT), emergency surgery, increasing length of case, and certain surgical services. BIS use was associated with previously documented risk factors for intraoperative awareness. These factors are also indicators of case complexity, which may be a major factor among providers deciding when to apply BIS monitoring in the operating room. PMID- 26897035 TI - Validity and reliability of arm abduction angle measured on smartphone: a cross sectional study. AB - BACKGROUND: Measuring range of movement is important in clinical shoulder assessment. Over the years, different techniques have been used to analyze upper limbs mobility. Smartphone image-based goniometer offers a noninvasive easy-to use method of measuring arm abduction angle. However, the validity of this method has not been previously established. The purpose of this study was to investigate the validity and reliability of an Internet and image-based app (mROM) regarding arm abduction angle in both healthy subjects and patients suffering from shoulder damage. METHODS: Twenty three subjects with shoulder pathology (14 female, 9 male) and 14 healthy subjects (8 female, 6 male) were examined (37 shoulders). mROM app was used to measure arm abduction angle. Two examiners measured 37 shoulders on 3 separate occasions over 2 days: 2 measurements on the first day and a third one the following day. Descriptive statistics were calculated for descriptive and anthropometric variables, as well as for the first measure of arm abduction angle by photographs and inertial sensors. Reliability was investigated by intraclass correlation coefficients and p values, and validity by Pearson correlation and P. RESULTS: Intra-rater and inter-rater reliability were high (intraclass correlation coefficients 0.998 and 0.984 respectively) for the total sample, although, for the healthy group, intrareliability was lower and interreliability was no reliable. Measurements from photographs and intertial sensors were highly correlated (Pearson r = 0.964) for the total sample. However, it was no significant for the healthy group. CONCLUSION: Smartphone photographs are a reliable and valid method to measure arm abduction angle, supporting the use of photography obtained through app for measuring joint ROM. This method provides a convenient and precise tool in assessment of arm motion. PMID- 26897036 TI - Prognostic role of HER2 amplification based on fluorescence in situ hybridization (FISH) in pancreatic ductal adenocarcinoma (PDAC): a meta-analysis. AB - BACKGROUND: Previous studies have shown that human epidermal growth factor receptor 2 (HER2) may play an important role in the invasion and metastasis of pancreatic cancer, but the relationship between HER2 amplification level and prognosis of pancreatic cancer patients is still controversial. Therefore, we performed a meta-analysis to determine the prognostic significance of HER2 amplification based on fluorescence in situ hybridization (FISH) in patients with pancreatic cancer. METHODS: PubMed, EMBASE, and Web of Science (Jan 2001 to Jun 2015) were searched. Only articles that detect the HER2 amplification by FISH method were included. RevMan 5.3 and STATA version 12 were used to perform this meta-analysis. Pooled calculations were carried out on hazard ratio (HR) and 95% confidence interval (CI) to assess the risk of disease. RESULTS: A total of six eligible studies were enrolled in meta-analysis. The univariate analysis results showed that HER2 amplification was not significantly associated with patients' overall survival (pooled HR, 1.87, 95% CI, 0.64-5.46, P=0.25), which are maintained in one study of multivariate analysis (HR 0.51, 95% CI, 0.12-2.14, P=0.358). HER2 amplification also had no correlation with clinicopathological factors such as age, gender, lymph node metastasis, and tumor stage. CONCLUSIONS: Our results showed that HER2 amplification based on FISH may not be a good prognostic factor for survival in patients with pancreatic cancer. PMID- 26897037 TI - Metabonomic biomarkers for risk factors of chronic kidney disease. AB - PURPOSE: Chronic kidney disease, characterized by gradual loss of renal function and irreversible progression, is becoming a major public health problem worldwide. Chronic kidney disease may lead to end-stage renal disease, as well as increase the morbidity and mortality associated with cardiovascular disease. METHODS: This review focuses on identifying risk factors indicating the need for intervention in early stages of chronic kidney disease, as well as determining factors that may improve patient prognosis. However, all the risk factors giving rise to the progression of chronic kidney disease have not yet been identified. RESULTS: Metabonomics is a new type of omics that reflects the real-time pathophysiology of disease and focuses on endogenous metabolites of low molecular weight. This new and powerful tool has recently been used to explore metabonomic biomarkers of chronic kidney disease, enabling early diagnosis and timely intervention and treatment to slow the progression of chronic kidney disease. CONCLUSIONS: This review summarizes recent findings on the identification, using a metabonomic approach, of biomarkers associated with risk factors for the development and progression of chronic kidney disease. PMID- 26897039 TI - Ophthalmic immunoglobulin G4-related disease IgG4-RD Current concepts. AB - IgG4-related disease (IgG4-RD) is a distinct entity that frequently occurs in an ophthalmic location. As such, IgG4-RD is not limited to the orbit but may also involve other anatomical structures in and around the eye. Hence, the term 'ophthalmic IgG4-RD' is preferred over 'orbital IgG4-RD.' A high level of suspicion for the diagnosis can be derived from careful clinicoradiologic examination; the use of immunohistochemical staining for IgG4 in the context of characteristic histopathologic features is needed to reach a correct diagnosis. Recently described diagnostic criteria for ophthalmic IgG4-RD address subtle, yet significant, differences from IgG4-RD as seen in other systemic sites. Serum IgG4 titers are neither sensitive nor specific for the diagnosis of IgG4-RD and should not relied upon solely. Although most cases respond well to therapy with glucocorticoids, refractoriness to treatment and relapses are common. They necessitate the use of additional immunotherapy in such patients. PMID- 26897038 TI - Peritoneal dialysis can be an option for unplanned chronic dialysis: initial results from a developing country. AB - AIM: Starting dialysis in an unplanned manner is frequent situation in dialysis center even for patients with regular nephrology follow-up. Peritoneal dialysis (PD) appears as an option for unplanned initiation of chronic dialysis, offering the advantage of not using central venous catheters and preserving of residual renal function. Since July 2014, we have offered PD as urgent start for chronic kidney disease (CKD) patients. METHODS: It was a prospective study that aimed to evaluate the mortality rate in hospitalized patients who started unplanned urgent PD in the first 90 days. It was used high-volume PD right after (<48 h) PD catheter placement, and it was kept until metabolic and fluid controls were achieved. After hospital discharge, patients were treated with intermittent PD on alternate days at the dialysis unit until family training. RESULTS: Thirty-five patients were included from July 2014 to January 2015. Age was 57.7 +/- 19.2 years, diabetes was the main etiology of CKD (40.6 %), and uremia was the main dialysis indication (54.3 %). Metabolic and fluid controls were achieved after five sessions of high-volume PD, and patients remained in intermittent PD for 23.2 +/- 7.2 days receiving 11.5 +/- .3.1 intermittent PD sessions. Peritonitis and mechanical complications occurred in 14.2 and 25.7 %, respectively. Mortality rate was 20 %, and technique survival was 85.7 %. The chronic PD program presented a growth of 41.1 %. CONCLUSION: The concept of unplanned start on chronic PD may be feasible, safe, complementary alternative to hemodialysis and a tool to increase the PD penetration rate among incident patients starting dialysis therapy. PMID- 26897041 TI - Collective invasion of cancer: Perspectives from pathology and development. AB - Clinical pathologists have long been aware that in many types of human malignant tumors, the cells are often connected and form groups of various sizes or "nests". In this way, they achieve "collective invasion" into the surrounding stroma, rather than spreading out individually. Such collective behavior is also a common feature of migration during embryonic and postnatal developmental stages, suggesting there are advantages gained by collective cell migration in the organisms. Recent studies have revealed the mechanisms underlying the collective invasion of cancer cells. These mechanisms differ from those observed in the migration of single cells in culture, including reliance on the epithelial mesenchymal transition program. Whereas intercellular adhesion appears to be coordinated, cancer cell groups can be heterogenous, including cells that are leaders and those that are followers. There is also interaction with the tumor microenvironment that is a prerequisite for collective invasion of cancer. In this review, we describe recently emerging mechanisms underlying the collective migration of cells, with a particular focus in our studies on the actin-binding protein Girdin/GIV and the transcriptional regulator tripartite motif containing 27. These studies provide new perspectives on the mechanistic analogy between cancer and development. PMID- 26897043 TI - ? PMID- 26897042 TI - Tertiary nitrogen removal for municipal wastewater using a solid-phase denitrifying biofilter with polycaprolactone as the carbon source and filtration medium. AB - Tertiary nitrogen removal technologies are needed to reduce the excess nitrogen that is discharged into sensitive aquatic ecosystems. An integrated solid-phase denitrification biofilter (SDNF) was developed with dual media to remove nitrate and suspended solids (SS) from the secondary effluent of municipal wastewater treatment plants. Biodegradable polymer pellets of polycaprolactone (PCL) served as the biofiltration medium and carbon source for denitrification. Long-term continuous operation of the SDNF was conducted with real secondary effluent to evaluate the denitrification performance and effects of influent nitrate loading rates (NLR) and operating temperatures. The results indicated that both nitrate and SS were effectively removed. The SDNF had a strong tolerance for fluctuations in influent NLR, and a maximum denitrification rate of 3.80 g N/(L.d) was achieved. The low temperature had a significant impact on nitrogen removal, yet the denitrification rate was still maintained at a relative high level to as much as 1.23 g N/(L.d) even at approximately 8.0 degrees C in winter. Nitrite accumulation and excessive organics residue in the effluent were avoided throughout the whole experiment, except on occasional days in the lag phase. The observed biomass yield was calculated to be 0.44 kgVSS/kgPCL. The microbial diversity and community structure of the biofilm in the SDNF were revealed by Illumina high-throughput sequencing. The special carbon source led to an obvious succession of microbial community from the initial inoculum (activated sludge from aerobic tanks), and included a decrease in microbial diversity and a shift in the dominant groups, which were identified to be members of the family Comamonadaceae in the SDNF. The SDNF developed in this study was verified to be an efficient technology for tertiary nitrogen removal from secondary effluent. PMID- 26897040 TI - Financial and Social Hardships in Families of Children with Medical Complexity. AB - OBJECTIVE: To describe hardships experienced by families of children with medical complexity (CMC) and compare them with those experienced by families of children with asthma. STUDY DESIGN: We assessed hardships in a cohort of 167 families of CMC. Surveys assessed sociodemographics and hardships (eg, financial: inability to pay bills; social: limited help from family/friends). CMC cohort hardships were compared with those of an established cohort of children hospitalized with asthma using multivariable logistic regression. RESULTS: CMC had diagnoses in a median of 5 different complex chronic condition categories (most common neurologic/neuromuscular), and the majority (74%) were dependent on technology. Over 80% of families of CMC reported experiencing >=1 hardship; 68% with financial and 46% with social hardship. Despite higher socioeconomic status than families with asthma, families of CMC often experienced more hardships. For example, families of CMC were significantly more likely to report failure to pay rent/mortgage (aOR 2.6, 95% CI 1.6, 4.3) and the expectation of little to no help from family/friends (aOR 2.9, 95% CI 1.9, 4.7). CONCLUSIONS: Families of CMC frequently report financial and social hardships, often at rates higher than families with asthma who were generally of lower socioeconomic status. Identifying and acting upon hardships may be an important addition to the care of CMC. PMID- 26897045 TI - Reaching a milestone in continuous assessment of quality colonoscopy skills: adding an ace to our assessment toolbox. PMID- 26897044 TI - A review and assessment of currently available data of the EGFR antibodies in elderly patients with metastatic colorectal cancer. AB - Although the number of elderly patients is increasing each year, this population has been under-represented in clinical trials. At the same time, the survival of patients with metastatic colorectal cancer has been improving, not only because of improvements in chemotherapy, but especially because of the addition of monoclonal antibodies (bevacizumab, cetuximab and panitumumab). Therefore, it is necessary to define the role of these new drugs in the elderly population, a group that is heterogeneous and consists of those who are fit and able to tolerate all therapies equally as well as younger patients and unfit individuals who should only given best supportive care or therapies specifically modulated for them. Today, although data from phase II-III studies have helped to establish the role of bevacizumab in the elderly, few trials have studied anti-epidermal growth factor receptor (EGFR) antibodies in the same population. This review presents the results of studies carried out with anti-EGFR agents, with a hope that more trials will be carried out with these drugs in the elderly in the future. PMID- 26897046 TI - It's all about the loop: quality indicators in pediatric colonoscopy. PMID- 26897047 TI - Colorectal cancer screening: 80% by 2018. Colonoscopists simply cannot do it alone. PMID- 26897048 TI - Whither the hyperplastic and serrated polyp? PMID- 26897049 TI - It's time to take the split-standard out of the split-prep. PMID- 26897050 TI - Hybrid endoscopic submucosal dissection in the colon: Cutting corners or trimming fat? PMID- 26897051 TI - Teaching endoscopic imaging should be more active. PMID- 26897052 TI - Against duodenobiliary reflux: implications from a randomized controlled trial. PMID- 26897053 TI - Response. PMID- 26897054 TI - Response. PMID- 26897055 TI - Resect and discard. PMID- 26897056 TI - Discrepancy in the classification of water immersion from water exchange colonoscopy. PMID- 26897057 TI - Response. PMID- 26897058 TI - HSV antivirals - current and future treatment options. AB - Herpes simplex virus (HSV) types 1 and 2 can cause infections with clinical manifestations ranging from benign and generally self-limiting blisters or sores as seen in labial and genital herpes through to severe and in rare cases even life-threatening infections. At present, approved treatments for herpes simplex virus are almost all nucleoside analogs. Novel antiviral approaches include therapeutic vaccines, with the most advanced having successfully completed Phase 2 clinical development. Moreover, several small molecules approaches are being developed for the treatment of genital or labial HSV infections. Of particular interest are two novel compounds (amenamevir and pritelivir) belonging to the new class of helicase-primase inhibitors with promising Phase 2 data. PMID- 26897059 TI - Ebola preparedness in Oman: An experience from the Middle East. PMID- 26897060 TI - The cauliflower-like black crusts on sandstones: A natural passive sampler to evaluate the surrounding environmental pollution. AB - Black crust in buildings can be formed as a result of different kind of chemical and physical reactions between the stone surface and environmental factors (e.g. acid aerosols emitted to the atmosphere, airborne particulate matter, etc.). Moreover, biological colonizations can also be present on them. This kind of pathology is widely present in limestones, but fewer are the case study dealing with the characterization of black crusts on sandstones. In this work we present an innovative methodology based on the use of cauliflower-like black crusts formed on sandstone material as natural passive sampler to evaluate the environmental pollution related with the emission of natural (crustal particles and marine aerosol particles) and metallic elements in the airborne particulate matter from the surrounding atmosphere. To illustrate its usefulness, different cauliflower-like black crusts growing in areas protected from the rain growing in an historical construction, La Galea Fortress, made up of sandstone and placed in the Abra Bay (Getxo, Basque Country, Spain) were characterized. This area suffers the anthropogenic emissions coming from the surrounding industry, traffic, sea port, and the natural ones coming from the surrounding marine atmosphere. The applied analytical methodology began with a previous elemental in situ screening in order to evaluate and compare the presence of the metals trapped in black crusts from different orientations using a hand-held energy dispersive X-Ray Fluorescence spectrometer. After this preliminary study, samples of black crusts were taken in order to characterize them in the laboratory using molecular techniques (Raman spectroscopy and XRD) and elemental techniques (ICP-MS, SEM-EDS and micro energy dispersive X-Ray Fluorescence). With the last two elemental techniques, imaging analyses were performed at different lateral resolutions in order to observe the distribution of the metals and other kind of particles trapped in the black crust samples. Additionally, a biological colonization found beneath the black crusts was also characterized using Phase Contrast microscopy. PMID- 26897061 TI - Health risks of polycyclic aromatic hydrocarbons via fish consumption in Haimen bay (China), downstream of an e-waste recycling site (Guiyu). AB - Guiyu, China has been one of the largest e-waste recycling sites of the world for more than 20 years. Abundant data show that local dwellers there suffered from severe health risks from e-waste contaminants. In this study, polycyclic aromatic hydrocarbons (PAHs) were used as candidates to test the contamination levels and their possible adverse effects on residents in Haimen Bay, the estuary of Lian River (less than 30km from Guiyu), which has been totally neglected. The concentrations of 16PAHs were determined in collected marine fish with a median SigmaPAH concentration of 1478ng/g (wet weight), and the contamination may be mainly influenced by Lian River runoff, specifically from Guiyu. The lifetime excess cancer risk for local dwellers was much higher than the serious risk level (10(-4)). More seriously, outflows of PAHs from the e-waste recycling site (Guiyu) seemed to exert health risks of a much larger scale of population downstream. PMID- 26897062 TI - Nonculture Diagnostics in Fungal Disease. AB - Fungal diagnostics that utilize antibody, antigen or nucleic acid detection offer several advantages that supplement traditional culture-based methods. As a group, nonculture assays can help identify patients with invasive fungal infection (IFI) sooner than is possible with culture, are often more sensitive, and can be used to guide early interventions. Challenges associated with these techniques include the possibility for contamination or cross-reactivity as well as the potential for false negative tests. This review summarized the test characteristics and clinical utility of nonculture-based laboratory methods. PMID- 26897063 TI - Basic Genetics and Immunology of Candida Infections. AB - Candida infections can cause superficial and invasive disease. Several essential mechanisms underlying the pathogenesis of these infections were known for some time, such as neutropenia predisposing to invasive disease, and CD4 lymphopenia causing increased susceptibility to mucosal candidiasis. However, the development of novel genetic screening techniques has led to several new insights in the genetics and immunology of candida infections. This article highlights novel insights in the pathogenesis of mucocutaneous and invasive candidiasis that have been identified in recent years. PMID- 26897064 TI - Invasive Aspergillosis: Current Strategies for Diagnosis and Management. AB - Aspergillosis remains a significant cause of morbidity and mortality in the immunocompromised population. The spectrum of disease is broad, ranging from severe and rapidly fatal infection to noninvasive disease. The diversity of patients and risk factors complicates diagnostic and therapeutic decision-making. Invasive procedures are often precluded by host status; noninvasive diagnostic tests vary in their sensitivity and specificity. Advancements in understanding the pathophysiology of invasive aspergillosis and host genetics in differential risk have also occurred. Future work may assist in therapeutic decision-making and patient prognosis. Voriconazole remains the preferred agent for treatment. Additional alternatives have emerged. PMID- 26897065 TI - Mucormycoses. AB - Life-threatening infections from virulent, angioinvasive molds of the order Mucorales are being recognized with increasing frequency in immunosuppressed hosts. Advances in the understanding of pathogenesis, early diagnosis, and the recent availability of active, nontoxic drugs have improved the prospects for effective control and even cure of this devastating infection. However, rates of delayed diagnosis and mortality are still high, partially because of the low yield and complexity of culture-based and molecular diagnostic methods. Therefore, there is an urgent need for novel diagnostic modalities and effective therapeutic approaches. PMID- 26897066 TI - Dematiaceous Molds. AB - Dematiaceous fungi are the cause of phaeohyphomycosis, a term that encompasses many clinical syndromes, from local infections due to trauma to widely disseminated infection in immunocompromised patients. These fungi are unique owing to the presence of melanin in their cell walls, which imparts the characteristic dark color to their spores and hyphae. Melanin may also be a virulence factor. Local infection may be cured with excision alone, whereas systemic disease is often refractory to therapy. Azoles have the most consistent in vitro activity. Further studies are needed to better understand the pathogenesis and treatment of these uncommon infections. PMID- 26897068 TI - Histoplasmosis. AB - Although histoplasmosis is highly endemic in certain regions of the Americas, disease may be seen globally and should not be overlooked in patients with unexplained pulmonary or systemic illnesses. Most patients exhibit pulmonary signs and symptoms, accompanied by radiographic abnormalities, which often are mistaken for community-acquired pneumonia caused by bacterial or viral agents. Once a diagnosis is considered, a panel of mycologic and non-culture-based assays is adequate to establish a diagnosis in a few days to a week in most patients. Once diagnosed, the treatment is highly effective even in immunocompromised patients. PMID- 26897069 TI - Fungal Infections. PMID- 26897070 TI - Detection of bladder metabolic artifacts in (18)F-FDG PET imaging. AB - Positron emission tomography using (18)F-fluorodeoxyglucose ((18)F-FDG-PET) is a widely used imaging modality in oncology. It enables significant functional information to be included in analyses of anatomical data provided by other image modalities. Although PET offers high sensitivity in detecting suspected malignant metabolism, (18)F-FDG uptake is not tumor-specific and can also be fixed in surrounding healthy tissue, which may consequently be mistaken as cancerous. PET analyses may be particularly hampered in pelvic-located cancers by the bladder's physiological uptake potentially obliterating the tumor uptake. In this paper, we propose a novel method for detecting (18)F-FDG bladder artifacts based on a multi feature double-step classification approach. Using two manually defined seeds (tumor and bladder), the method consists of a semi-automated double-step clustering strategy that simultaneously takes into consideration standard uptake values (SUV) on PET, Hounsfield values on computed tomography (CT), and the distance to the seeds. This method was performed on 52 PET/CT images from patients treated for locally advanced cervical cancer. Manual delineations of the bladder on CT images were used in order to evaluate bladder uptake detection capability. Tumor preservation was evaluated using a manual segmentation of the tumor, with a threshold of 42% of the maximal uptake within the tumor. Robustness was assessed by randomly selecting different initial seeds. The classification averages were 0.94+/-0.09 for sensitivity, 0.98+/-0.01 specificity, and 0.98+/ 0.01 accuracy. These results suggest that this method is able to detect most (18)F-FDG bladder metabolism artifacts while preserving tumor uptake, and could thus be used as a pre-processing step for further non-parasitized PET analyses. PMID- 26897071 TI - Advising patients on selecting trustful apps for diabetes self-care. AB - BACKGROUND: There has been a dramatic increase in mobile apps for diabetes self care. However, their quality is not guaranteed and patients do not have the appropriate tools for careful evaluation. OBJECTIVE: This work aims to propose a tool to help patients with diabetes select an appropriate app for self-care. METHODS: After identifying the conceptual framework of diabetes self-care, we searched Apple US app store and reviewed diabetes self-care apps, considering both generic and diabetes-specific features. Based on an existing tool for representing the benefits and weaknesses of medical apps, we created the pictorial identification schema/Diabetes Self-care tool, which specifically identified medical apps in the diabetes domain. RESULTS: Of the 952 apps retrieved, 67 were for diabetes self-care, while 26 were excluded because they were not updated in the last 12 months. Of the remaining 41, none cost more than 15 USD, and 36 implemented manual data entry. Basic features (data logging, data representation, and data delivery) were implemented in almost all apps, whereas advanced features (e.g., insulin calculator) were implemented in a small percentage of apps. The pictorial identification schema for diabetes was completed by one patient and one software developer for 13 apps. Both users highlighted weaknesses related to the functionalities offered and to their interface, but the patient focused on usability, whereas the software developer focused on technical implementation. CONCLUSIONS: The Pictorial Identification Schema/Diabetes Self-care is a promising graphical tool for perceiving the weaknesses and benefits of a diabetes self-care app that includes multiple user profile perspectives. PMID- 26897072 TI - Neil Armstrong syndrome. PMID- 26897073 TI - Paradoxical coronary artery embolism due to patent foramen ovale. PMID- 26897067 TI - Cryptococcosis. AB - Cryptococcosis is an invasive mycosis caused by pathogenic encapsulated yeasts in the genus Cryptococcus. Cryptococcus gained prominence as a pathogen capable of widespread disease outbreaks in vulnerable populations. We have gained insight into the pathobiology of Cryptococcus, including the yeast' s capacity to adapt to environmental pressures, exploit new geographic environments, and cause disease in both immunocompromised and apparently immunocompetent hosts. Inexpensive, point-of-care testing makes diagnosis more feasible than ever. The associated worldwide burden and mortality remains unacceptably high. Novel screening strategies and preemptive therapy offer promise at making a sustained and much needed impact on this sugar-coated opportunistic mycosis. PMID- 26897074 TI - Could ten questions asked by the dispatch center predict the outcome for patients with chest discomfort? AB - BACKGROUND AND AIMS: From 2009 to 2010, approximately 14,000 consecutive persons who called for the EMS due to chest discomfort were registered. From the seventh month, dispatchers ask 2285 patient ten pre-specified questions. We evaluate which of these questions was independently able to predict an acute coronary syndrome (ACS), life-threatening condition (LTC) and death. METHODS: The questions asked mainly dealt with previous history and type of symptoms, each with yes/no answers. The dispatcher took a decision on priority; 1) immediately with sirens/blue light; 2) EMS on the scene within 30min; 3) normal waiting time.We examined the relationship between the answers to these questions and subsequent dispatch priority, as well as outcome, in terms of ACS, LTC and all cause mortality. RESULTS: 2285 patients (mean age 67years, 49% women) took part, of which 12% had a final diagnosis of ACS and 15% had a LTC. There was a significant relationship between all the ten questions and the priority given by dispatchers. Localisation of the discomfort to the center of the chest, more intensive pain, history of angina or myocardial infarction as well as experience of cold sweat were the most important predictors when evaluating the probability of ACS and LTC. Not breathing normally and having diabetes were related to 30-day mortality. CONCLUSIONS: Among individuals, who call for the EMS due to chest discomfort, the intensity and the localisation of the pain, as well as a history of ischemic heart disease, appeared to be the most strongly associated with outcome. PMID- 26897075 TI - The role of anti-myosin antibodies in perpetuating cardiac damage following myocardial infarction. AB - Recent improvements in the medical and surgical management of myocardial infarction mean that many patients are now surviving with greater impairment of cardiac function. Despite appropriate management, some of these patients subsequently develop pathological ventricular remodelling, which compounds their contractile dysfunction and can lead to congestive cardiac failure (CCF). The pathophysiological mechanism underpinning this process remains incompletely understood. One hypothesis suggests that a post-infarction autoimmune response, directed against constituents of cardiac myocytes, including cardiac myosin, may make an important contribution. Our review summarises the current literature related to the formation and clinical relevance of anti-myosin antibodies (AMAs) in patients with myocardial infarction. This discussion is supplemented with reference to a number of important animal studies, which provide evidence of the potential mechanisms underlying AMA formation and autoantibody mediated cardiac dysfunction. PMID- 26897076 TI - Exercise restrictions for patients with inherited cardiac conditions: Current guidelines, challenges and limitations. AB - Inherited primary arrhythmia syndromes are a clinically heterogeneous group of relatively uncommon but important inherited cardiac conditions that are associated with an increased risk of sudden cardiac death (SCD) in the setting of a structurally normal heart. These include long-QT syndrome (LQTS), Short-QT syndrome (SQTS), Brugada syndrome (BrS) and Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT). The cardiomyopathies represent the other major group of inherited cardiac conditions associated with SCD, of which hypertrophic cardiomyopathy (HCM) is the most common. Exercise is a known trigger of ventricular arrhythmias in many of these conditions, however marked genetic and clinical heterogeneity within individual diseases means that certain patients are at a much greater risk of lethal ventricular arrhythmias during exercise than others. For instance, LQTS type 1 (LQT1) and CPVT patients are at particular risk during exertion, whilst in patients with other genetic variants of LQTS, BrS and SQTS, alternative triggers are more significant precipitants. Many channelopathy (principally Brugada, CPVT) & cardiomyopathy (mainly HCM) patients receive primary or secondary prevention therapy with an implantable cardiac defibrillator (ICD). Exercising with an ICD in situ carries a range of additional risks including inappropriate shocks and lead complications. This review will focus on the risk of exercise-induced SCD in patients with inherited cardiac conditions, the current clinical guidelines in this area and the special consideration of patients with an ICD. PMID- 26897079 TI - Are women delaying in attending to both their own health care and making decisions on the acute phase of myocardial infarction? PMID- 26897077 TI - The role of cystatin C as a biomarker for prognosis in pulmonary arterial hypertension due to congenital heart disease. AB - BACKGROUND: Adults with pulmonary arterial hypertension due to congenital heart disease (PAH-CHD) have a poor prognosis. Identifying patients with a high risk for clinical events and death is important because their prognosis can be improved by intensifying their treatment. Cystatin C, a novel cardiac biomarker, correlates with right ventricular dimensions in patients with idiopathic PAH, giving it potential to determine prognosis in PAH-CHD patients. We investigated the predictive value of cystatin C for long-term mortality and clinical events. METHODS: Fifty-nine PAH-CHD patients (mean age 42 SD 13 years, 42% male) were included in this prospective observational study, with cystatin C measurements between 2005 and 2015 on the outpatient clinic. Patients were evaluated with a standardized evaluation protocol including laboratory, functional and echocardiographic variables. Clinical events comprised worsening functional classification, worsening heart failure, symptomatic hyperviscosity, haemoptysis and arrhythmia. We used Cox regression to determine predictors for mortality and clinical events. RESULTS: Mean follow-up was 4.4years, during which 12 (20%) patients died. Cystatin C (HR 1.3, p<0.001), creatinine (HR 1.2, p<0.001), NT-pro BNP (HR 2.0, p=0.012), hs-troponin T (HR 1.9, p=0.005), 6-MWD (HR 0.8, p=0.044) and TAPSE (HR 0.8, p<0.001) predicted mortality. Similar results were found for the prediction of clinical events. When adjusted for NT-pro-BNP or glomerular filtration rate in multivariate analysis, cystatin C remained predictive for mortality. CONCLUSIONS: Cystatin C, a novel cardiac biomarker, predicts long-term mortality and clinical events in patients with PAH-CHD. Consequently, cystatin C may attribute to clinical decision making regarding treatment intensity. PMID- 26897080 TI - Differential diagnosis of arrhythmogenic right ventricular cardiomyopathy and granulomatous myocarditis by advanced ECG analysis. PMID- 26897078 TI - Familial lamin A/C mutation cardiomyopathy with arrhythmia substrate detected by cardiac magnetic resonance imaging and electroanatomical mapping. PMID- 26897081 TI - Is there still a role for additional linear ablation in addition to pulmonary vein isolation in patients with paroxysmal atrial fibrillation? An Updated Meta analysis of randomized controlled trials. AB - BACKGROUND: The benefits and risks of additional left atrium (LA) linear ablation in patients with paroxysmal atrial fibrillation (AF) remain unclear. METHODS: Randomized controlled trials were identified in the PubMed, Web of Science, Embase and Cochrane databases, and the relevant papers were examined. Pooled relative risks (RR) and 95% confidence interval (95% CI) were estimated using random effects models. The primary endpoint was the maintenance of sinus rhythm after a single ablation. RESULTS: Nine randomized controlled trials involving 1138 patients were included in this analysis. Additional LA linear ablation did not improve the maintenance of the sinus rhythm following a single procedure (RR, 1.03; 95% CI, 0.93-1.13; P=0.60). A subgroup analysis demonstrated that all methods of additional linear ablation failed to improve the outcome. Additional linear ablation significantly increased the mean procedural time (166.53+/-67.7 vs. 139.57+/-62.44min, P<0.001), the mean fluoroscopy time (54.56+/-38.7 vs. 44.32+/-31.6min, P<0.001) and the mean radiofrequency (RF) energy application time (78.94+/-28.39 vs. 59.74+/-22.38min, P<0.001). No statistically significant differences in the rates of complications were noted (RR, 0.57; 95% CI, 0.27 1.19; P=0.13). CONCLUSIONS: Additional LA linear ablation did not exhibit any benefits in terms of sinus rhythm maintenance for paroxysmal AF patients following a single procedure. Additional linear ablation significantly increased the mean procedural, fluoroscopy and RF application times. This additional ablation was not associated with a statistically significant increase in complication rates. This finding must be confirmed by further large, high-quality clinical trials. PMID- 26897082 TI - Ecological proteomics: is the field ripe for integrating proteomics into evolutionary ecology research? PMID- 26897083 TI - Behaviour of butyltin compounds in the sediment pore waters of a contaminated marina (Port Camargue, South of France). AB - Despite the ban on tributyltin (TBT) in marine paints, harbour sediments are still highly contaminated by this antifouling agent. Concentrations of TBT and its dealkylated products dibutyltin (DBT) and monobutyltin (MBT) were determined in the pore waters of Port Camargue, a large marina located on the French Mediterranean coast. Pore waters were sampled in the field using peepers deployed in summer 2012 and 2013 and in winter 2012-2013. The winter surveys were characterized by the presence of sulphides in pore waters from a depth of 5 cm, which was not the case in winter. In summer 2013, TBT was shown to be released into pore waters below the sediment-water interface (SWI) at concentrations of up to 70 ngSn L(-1). This release was also observed in sediment anaerobic incubations and was attributed to the mineralization of the sedimentary organic matter, possible stabilization of TBT by complexation with sulphides, and lower debutylation rates in anoxic than in oxic conditions. In summer 2012, a comparatively lower concentration of TBT (around 20 ngSn L(-1) below the SWI) was measured and the presence of methyltin species was detected. We hypothesize that the differences between the two surveys reflect different microbial activity. In winter 2012-2013, marked by Fe-reducing conditions in the sediments, TBT was released into solution at the SWI at concentrations of up to 40 ngSn L(-1). Sediments are thus a continuing source of TBT for the overlying waters despite the ban on its use for boats in France. PMID- 26897084 TI - Computational studies on receptor-ligand interactions between novel buffalo (Bubalus bubalis) nucleotide-binding oligomerization domain-containing protein 2 (NOD2) variants and muramyl dipeptide (MDP). AB - Nucleotide binding and oligomerization domain 2 (NOD2), a member of intracellular NOD-like receptors (NLRs) family, recognizes the bacterial peptidoglycan, muramyl dipeptide (MDP) and initiates host immune response. The precise ligand recognition mechanism of NOD2 has remained elusive, although studies have suggested leucine rich repeat (LRR) region of NOD2 as the possible binding site of MDP. In this study, we identified multiple transcripts of NOD2 gene in buffalo (buNOD2) and at least five LRR variants (buNOD2-LRRW (wild type), buNOD2-LRRV1 V4) were found to be expressed in buffalo peripheral blood mononuclear cells. The newly identified buNOD2 transcripts were shorter in lengths as a result of exon skipping and frame-shift mutations. Among the variants, buNOD2-LRRW, V1, and V3 were expressed more frequently in the animals studied. A comparative receptor ligand interaction study through modeling of variants, docking, and molecular dynamics simulation revealed that the binding affinity of buNOD2-LRRW towards MDP was greater than that of the shorter variants. The absence of a LRR segment in the buNOD2 variants had probably affected their affinity toward MDP. Notwithstanding a high homology among the variants, the amino acid residues that interact with MDP were located on different LRR motifs. The binding free energy calculation revealed that the amino acids Arg850(LRR4) and Glu932(LRR7) of buNOD2 LRRW, Lys810(LRR3) of buNOD2-LRRV1, and Lys830(LRR3) of buNOD2-LRRV3 largely contributed towards MDP recognition. The knowledge of MDP recognition and binding modes on buNOD2 variants could be useful to understand the regulation of NOD mediated immune response as well as to develop next generation anti-inflammatory compounds. PMID- 26897085 TI - MicroRNA-23a reduces slow myosin heavy chain isoforms composition through myocyte enhancer factor 2C (MEF2C) and potentially influences meat quality. AB - MicroRNAs (miRNAs) are non-coding small RNAs that participate in the regulation of a variety of biological processes. Muscle fiber types were very important to meat quality traits, however, the molecular mechanism by which miRNAs regulate the muscle fiber type composition is not fully understood. The aim of this study was to investigate whether miRNA-23a can affect muscle fiber type composition. Luciferase reporter assays proved that miRNA-23a directly targets the 3' untranslated region (UTRs) of MEF2c. Overexpression of miRNA-23a significantly suppressed the expression of MEF2c both in mRNA and protein levels, thus caused down-regulation of the expression of some key downstream genes of MEF2c (PGC1 alpha, NRF1 and mtTFA). More interestingly, overexpression of miRNA-23a significantly restrained the myogenic differentiation and decreased the ratio of slow myosin heavy chain in myoblasts (p<0.05). Our findings hinted a novel role of miRNA-23a in the epigenetic regulation of meat quality via decreasing the ratio of slow myosin heavy chain isoforms. PMID- 26897086 TI - Influence of cutting and deboning operations on the microbiological quality and shelf life of buffalo meat. AB - Considering the specific biochemical composition of buffalo (Bubalus bubalis) meat (high iron content, high biological value proteins and essential fatty acids, low amounts of fat and cholesterol), we evaluated the influence of cutting and deboning operations on the microbiological quality and shelf-life of vacuum packed buffalo meat stored under refrigeration. On the processing day, samples were collected from carcass, deboning room surfaces and meat cuts. Samples from meat cuts were evaluated weekly for two months. On the processing day, higher counts of Pseudomonas spp. were observed in samples from meat cuts compared with the hindquarters and the processing surfaces. For thermotolerant coliform scores, the averages were -0.5 log MPN.cm(-2), -0.4 log MPN.cm(-2) and 0.9 log MPN.g(-1), respectively. Higher counts of Pseudomonas spp. and LAB in meat cuts were observed on the processing day and after the first week of storage, respectively, remaining constant during shelf life. Listeria grayi was identified in two samples of hindquarters and meat cuts during storage. Listeria innocua was identified in one meat cut. In conclusion, cutting and deboning operations influence the microbiological quality and shelf life of vacuum-packed buffalo meat stored under refrigeration. PMID- 26897087 TI - Endocrine-disruptor molecular responses, occurrence of intersex and gonado histopathological changes in tilapia species from a tropical freshwater dam (Awba Dam) in Ibadan, Nigeria. AB - In the present study, the occurrence of endocrine disruptive responses in Tilapia species from Awba Dam has been investigated, and compared to a reference site (Modete Dam). The Awba Dam is a recipient of effluents from University of Ibadan (Nigeria) and several other anthropogenic sources. A total of 132 Tilapia species (Sarotherodon malenotheron (n=57 and 32, males and females, respectively) and Tilapia guineensis (n=23 and 20, males and females, respectively)) were collected from June to September 2014. At the reference site, samples of adult male and female S. melanotheron (48 males and 47 females) and T. guineensis (84 males and 27 females) were collected. Gonads were morphologically and histologically examined and gonadosomatic index (GSI) was calculated. Hepatic mRNA transcriptions of vitellogenin (Vtg) and zona radiata protein (Zrp) genes were analyzed using validated RT-qPCR. Significant increase in Vtg and Zrp transcripts were observed in male tilapias from Awba Dam, compared to males from the reference site. In addition, male tilapias from Awba Dam produced significantly higher Vtg and Zrp mRNA, compared to females in June and July. However, at the natural peak spawning period in August and September, females produced, significantly higher Vtg and Zrp mRNA, compared to males. Fish gonads revealed varying incidence of intersex with a striking presence of two (2) pairs of testes and a pair of ovary in S. melanotheron from Awba Dam. The entire fish population examined at Awba Dam showed a high prevalence of intersex (34.8%), involving phenotypic males and females of both species. Analysis of sediment contaminant levels revealed that As, Cd, Pb, Hg and Ni (heavy metals), monobutyltin cation, 4 iso-nonyphenol and PCB congeners (138, 153 and 180) were significantly higher in Awba Dam, compared to the reference site. Principal component analysis (PCA) showed that fish variables were positively correlated with sediment contaminant burden at Awba Dam, indicating that the observed endocrine disruptive responses are associated with contaminant concentrations. Overall, the occurrence of intersex and elevated expressions of Vtg and Zrp in male fish, suggest that the measured contaminants were eliciting severe endocrine disruptive effects in Awba Dam biota, which is an important source of domestic water supply and fisheries for the University of Ibadan community. PMID- 26897088 TI - Effects of 17alpha-ethinylestradiol at different water temperatures on zebrafish sex differentiation and gonad development. AB - In the current climate change scenario, studies combining effects of water contaminants with environmental parameters, such as temperature, are essential to predict potentially harmful impacts on aquatic organisms. In zebrafish (Danio rerio), sex determination seems to have a polygenic genetic basis, which can be secondarily influenced by environmental factors, such as temperature and endocrine disrupting chemicals (EDCs). The present study aimed to evaluate the effects of the EDC 17alpha-ethinylestradiol (EE2), a potent synthetic estrogen, on zebrafish sex differentiation and gonad development at different water temperatures. Therefore, zebrafish raised at three distinct water temperatures (23, 28 or 33+/-0.5 degrees C), were exposed to 4ng/L of EE2, from 2hours to 60days post-fertilization (dpf). Subsequently, a quantitative (stereological) assessment of zebrafish gonads was performed, at 35 and 60dpf, to identify alterations on gonadal development and differentiation. The results show that low temperature delayed general growth of zebrafish, as well as gonad differentiation and maturation, while high temperature induced an opposite effect. Moreover, sex ratio was skewed toward males when zebrafish were exposed to the high temperature. In general, EE2 exposure promoted gonad maturation in both genders, independently of the temperature. However, at the high temperature condition, exposure to EE2 induced a delay in the male gonad development, with some individuals still showing differentiating gonads at 60dpf. The findings of this study support the notion that zebrafish has a genetic sex determination mechanism highly sensitive to environmental factors and show that it is essential to study the effects of water contaminants at different climate scenarios in order to understand potential future impacts on organisms. PMID- 26897089 TI - Identification of spirooxindole and dibenzoxazepine motifs as potent mineralocorticoid receptor antagonists. AB - Mineralocorticoid receptor (MR) antagonists continue to be a prevalent area of research in the pharmaceutical industry. Herein we report the discovery of various spirooxindole and dibenzoxazepine constructs as potent MR antagonists. SAR analysis of our spirooxindole hit led to highly potent compounds containing polar solubilizing groups, which interact with the helix-11 region of the MR ligand binding domain (LBD). Various dibenzoxazepine moieties were also prepared in an effort to replace a known dibenzoxepane system which interacts with the hydrophobic region of the MR LBD. In addition, an X-ray crystal structure was obtained from a highly potent compound which was shown to exhibit both partial agonist and antagonist modes of action against MR. PMID- 26897090 TI - Design, synthesis and biological evaluation of novel 4-phenoxy-6,7-disubstituted quinolines possessing (thio)semicarbazones as c-Met kinase inhibitors. AB - In continuing our efforts to identify small molecules able to inhibit c-Met kinase, three series of novel 6,7-disubstituted-4-phenoxyquinoline derivatives (23a-w, 26a-d and 30a-d) bearing (thio)semicarbazone scaffold were designed, synthesized and evaluated for their cytotoxicity. The biological data revealed that most compounds exhibited moderate-to-excellent activity against HT-29, MKN 45, A549 cancer cell lines and relative poor potency toward MDA-MB-231 cell as well as hardly any cytotoxicity in normal PBL cell. Eleven compounds were further examined for their inhibitory activity against c-Met kinase and three compounds (23h, 23n and 26a) demonstrated good inhibitory activity. This work resulted in the discovery of a potent c-Met inhibitor 23n, bearing 2-hydroxy-3-allylphenyl group at R(2) moiety, as a valuable lead molecule, which possessed remarkable cytotoxicity and high selectivity against A549 and HT-29 cell lines with IC50 values of 11 nM and 27 nM. Besides, it displayed excellent c-Met kinase inhibition on a single-digital nanomolar level (IC50=1.54 nM). Meanwhile, the results from preliminarily in vivo study reflected that compound 23n showed promising overall PK profiles, consistent with the efficacy in both MKN-45 and HT 29 tumor xenograft mice model. These results clearly indicated that compound 23n is a potent and highly selective c-Met inhibitor and its favorable in vitro and in vivo profiles warrant further investigation. PMID- 26897091 TI - New derivative of 2-(2,4-dihydroxyphenyl)thieno-1,3-thiazin-4-one (BChTT) elicits antiproliferative effect via p38-mediated cell cycle arrest in cancer cells. AB - 2-(2,4-Dihydroxyphenyl)thieno-1,3-thiazin-4-ones are a group of new compounds with potential anticancer activity. This type of derivatives was poorly investigated in the area of synthesis and biological activities. In the present study the antiproliferative action of the most active derivative BChTT was described. The aim of biological evaluation was to investigate the ability of the compound to inhibit cancer cell proliferation and identify mechanism involved in its action on the molecular level. BChTT inhibited the proliferation of lung cancer A549, colon cancer HT-29 and glioma C6 cells in the concentration dependent manner. It was not toxic to normal cells including skin fibroblasts, hepatocytes and oligodendrocytes in the antiproliferative concentrations. BChTT decreased the DNA synthesis in the treated cancer cells and induced cell cycle arrest in the G0/G1 phase. Moreover, the ability of the compound to activate p38 kinase and decrease cyclin D1 expression was estimated. Participation of p38 kinase in the antiproliferative action of the compound was confirmed by the analysis of BChTT activity in the cells with the p38 silenced gene. The obtained results may suggest the ability of the tested derivative to inhibit cancer cells proliferation by induction of p38-mediated cyclin D1 downregulation. PMID- 26897092 TI - Statin-associated cerebellar ataxia. A Brazilian case series. AB - BACKGROUND: Drug-induced cerebellar ataxias (DICA) represent an important group of secondary cerebellar ataxias. Herein, we reported a case series of progressive cerebellar ataxia induced by HMG-CoA reductase inhibitors (statins). METHODS: Observational study with a Brazilian case series of patients with cerebellar ataxia due to statins use. RESULTS: We described four patients with cerebellar ataxia, predominantly gait ataxia, due to statins use. Mean age was 67.5 years old, predominantly male, with several comorbidities, such as dyslipidemia, diabetes mellitus, hypertension, and myocardial revascularization. After statin withdrawal, and treatment with coenzyme Q10 in some patients, progressive improvement of gait ataxia was observed. DISCUSSION: We presented a case series of four patients with cerebellar ataxia due to statins use, which represents a new rare side-effect of statins, probably related to coenzyme Q10 deficiency. PMID- 26897093 TI - Mechanical properties and failure analysis of visible light crosslinked alginate based tissue sealants. AB - Moderate to weak mechanical properties limit the use of naturally-derived tissue sealants for dynamic medical applications, e.g., sealing a lung leak. To overcome these limitations, we developed visible-light crosslinked alginate-based hydrogels, as either non-adhesive methacrylated alginate (Alg-MA) hydrogel controls, or oxidized Alg-MA (Alg-MA-Ox) tissue adhesive tissue sealants, which form covalent bonds with extracellular matrix (ECM) proteins. Our study investigated the potential for visible-light crosslinked Alg-MA-Ox hydrogels to serve as effective surgical tissue sealants for dynamic in vivo systems. The Alg MA-Ox hydrogels were designed to be an injectable system, curable in situ. Burst pressure experiments were conducted on a custom-fabricated burst pressure device using constant air flow; burst pressure properties and adhesion characteristics correlated with the degrees of methacrylation and oxidation. In summary, visible light crosslinked Alg-MA-Ox hydrogel tissue sealants form effective seals over critically-sized defects, and maintain pressures up to 50mm Hg. PMID- 26897094 TI - Numerical modeling of experimental human fibrous cap delamination. AB - Fibrous cap delamination is a critical process during the rupture of atherosclerotic plaque, which often leads to severe life-threatening clinical consequences such as myocardial infarction or stroke. In this study a finite element modeling and simulation approach is presented that enables the study of fibrous cap delamination experiments for the purpose of understanding the fibrous cap delamination process. A cohesive zone model (CZM) approach is applied to simulate delamination of the fibrous cap from the underlying plaque tissue. A viscoelastic anisotropic (VA) model for the bulk arterial material behavior is extended from existing studies so that the hysteresis phenomenon observed in the fibrous cap delamination experiments can be captured. A finite element model is developed for the fibrous cap delamination experiments, in which arterial layers (including the fibrous cap and the underlying plaque tissue) are represented by solid elements based on the VA model and the fibrous cap-underlying plaque tissue interface is characterized by interfacial CZM elements. In the CZM, the delamination process is governed by an exponential traction-separation law which utilizes critical energy release rates obtained directly from the fibrous cap delamination experiments. A set of VA model parameter values and CZM parameter values is determined based on values suggested in the literature and through matching simulation predictions of the load vs. load-point displacement curve with one set of experimental measurements. Using this set of parameter values, simulation predictions for other sets of experimental measurements are obtained and good agreement between simulation predictions and experimental measurements is observed. Results of this study demonstrate the applicability of the viscoelastic anisotropic model and the CZM approach for the simulation of diseased arterial tissue failure processes. PMID- 26897095 TI - Characterization of mechanical properties of hydroxyapatite-silicon-multi walled carbon nano tubes composite coatings synthesized by EPD on NiTi alloys for biomedical application. AB - Release of Ni(1+) ions from NiTi alloy into tissue environment, biological response on the surface of NiTi and the allergic reaction of atopic people towards Ni are challengeable issues for biomedical application. In this study, composite coatings of hydroxyapatite-silicon multi walled carbon nano-tubes with 20wt% Silicon and 1wt% multi walled carbon nano-tubes of HA were deposited on a NiTi substrate using electrophoretic methods. The SEM images of coated samples exhibit a continuous and compact morphology for hydroxyapatite-silicon and hydroxyapatite-silicon-multi walled carbon nano-tubes coatings. Nano-indentation analysis on different locations of coatings represents the highest elastic modulus (45.8GPa) for HA-Si-MWCNTs which is between the elastic modulus of NiTi substrate (66.5GPa) and bone tissue (~30GPa). This results in decrease of stress gradient on coating-substrate-bone interfaces during performance. The results of nano-scratch analysis show the highest critical distance of delamination (2.5mm) and normal load before failure (837mN) as well as highest critical contact pressure for hydroxyapatite-silicon-multi walled carbon nano-tubes coating. The cell culture results show that human mesenchymal stem cells are able to adhere and proliferate on the pure hydroxyapatite and composite coatings. The presence of both silicon and multi walled carbon nano-tubes (CS3) in the hydroxyapatite coating induce more adherence of viable human mesenchymal stem cells in contrast to the HA coated samples with only silicon (CS2). These results make hydroxyapatite-silicon-multi walled carbon nano-tubes a promising composite coating for future bone implant application. PMID- 26897096 TI - Portuguese Pulmonology footprint in Europe: From abstracts to papers and grants. PMID- 26897097 TI - Holoprosencephaly and Pure Red Cell Aplasia in a Feline Leukaemia Virus-Positive Kitten. AB - A 9-month-old, female, domestic longhair cat with severe anaemia tested positive for feline leukaemia virus (FeLV) and was humanely destroyed and submitted for necropsy examination. Gross findings included a non-divided rostral telencephalon, consistent with semilobar holoprosencephaly. Histological examination of the bone marrow revealed an almost complete absence of erythroid precursor cells, consistent with pure red cell aplasia, and mild to moderate myelofibrosis. This case demonstrates a very unusual central nervous system defect, as well as an atypical presentation of pure red cell aplasia, in a FeLV positive kitten. PMID- 26897098 TI - Association of polymorphisms of adiponectin gene promoter-11377C/G, glutathione peroxidase-1 gene C594T, and cigarette smoking in nonalcoholic fatty liver disease. AB - BACKGROUND: The number of studies on adiponectin, GPx-1 gene polymorphisms, and nonalcoholic fatty liver disease (NAFLD) susceptibility is increasing, but none have investigated the effect of cigarette smoking in combination with the gene polymorphisms on the susceptibility to NAFLD. In order to understand the distribution of adiponectin and GPx-1 in the local population, to explore the possible association of cigarette smoking with adiponectin and GPx-1 gene polymorphisms in the pathogenesis of NAFLD, we conducted this research, examining the distribution of polymorphisms of adiponectin and GPx-1 in NAFLD patients and healthy controls, analyzing the association between these polymorphisms and cigarette smoking. METHODS: Two hundred nonalcoholic simple fatty liver (NAFL), 200 nonalcoholic steatohepatitis (NASH), and 200 nonalcoholic fatty hepatic cirrhosis (NAFHC) cases from the First Affiliated Hospital of Xinxiang Medical College in China from February 2011 to November 2014 were selected for this study, and 200 healthy individuals as a control group. No significant difference among the four groups in age, sex, ethnicity, and birthplace was observed. The genetic polymorphisms of adiponectin gene promoter-11377C/G and GPx-1 gene C594T were analyzed using polymerase chain reaction-restriction fragment length polymorphisms in peripheral blood leukocytes of the above-mentioned cases. The interaction between the two mutants and the gene-environment association of the genotypes with cigarette smoking were analyzed. RESULTS: The frequencies of adiponectin gene promoter-11377C/G(CG), -11377C/G (GG), GPx-1 gene C594T (CT) and C594T (TT) were 24.50%, 26.00%, 24.00%, and 25.50% in the NAFL group, 34.50%, 37.00%, 35.00%, and 36.00% in the NASH group, 42.00%, 46.00%, 43.50%, and 45.50% in the NAFHC group, and 14.00%, 14.50%, 13.00%, and 14.00% in the control group, respectively. Statistical tests showed a significant difference in the frequencies among each group (p < 0.01). The risk of NAFLD significantly increased in patients with adiponectin gene promoter-11377C/G (CG) genotype [odds ratio (OR)NAFL = 2.5278; ORNASH = 6.1823; ORNAFHC = 17.8570), in those with 11377C/G (GG) genotype (ORNAFL = 2.5900; ORNASH = 6.4017; ORNAFHC = 18.9023), in those with GPx-1 gene C594T (CT) genotype (ORNAFL = 2.6687; ORNASH = 6.7772; ORNAFHC = 22.2063), and in those with C594T (TT) genotype (ORNAFL = 2.6330; ORNASH = 6.4729; ORNAFHC = 21.5682). Combined analysis of the polymorphisms showed that percentages of adiponectin gene promoter -11377C/G (GG)/GPx-1 gene C594T (TT) in the NAFL, the NASH, NAFHC, and control groups was 7.00%, 13.50%, 21.00%, and 2.00%, respectively (p < 0.01). The people who carried the adiponectin gene promoter -11377C/G (GG)/GPx-1 gene C594T (TT) had a high risk of NAFLD (ORNAFL = 7.2800; ORNASH = 41.2941; ORNAFHC = 363.9724), and statistical analysis suggested a positive association between -11377C/G (GG) and C594T (TT) in increasing the risk of NAFLD (gamma2NAFL = 2.2071, gamma4 NAFL = 2.0773; gamma2 NASH = 2.1084; gamma4NASH = 2.0543; gamma2 NAFHC = 2.1387; gamma4NAFHC = 2.0004). Likewise, there were also positive association in the pathogenesis of NAFLD between -11377C/G (CG) and C594T (TT), -11377C/G (CG) and C594T (CT), 11377C/G (GG), and C594T (TT) (CT).The frequencies of smoking index (SI) <= 400 and SI > 400 were 22.50% and 26.50% in the NAFL group, 29.00% and 40.50% in the NASH group, 34.00% and 51.50% in the NAFHC group, and 15.50% and 12.00% in the control group, respectively. Statistical tests showed a significant difference in the frequencies among each group (all p < 0.01). The risk of NAFLD significantly increased in patients with SI <= 400 (ORNAFL = 2.0636; ORNASH = 4.4474; ORNAFH C = 10.9677) and in those with SI > 400 (ORNAFL = 3.1393; ORNASH = 8.0225; ORNAFHC = 21.4583), and statistical analysis suggested a positive association between cigarette smoking and -11377C/G (CG), -11377C/G (GG), C594T (CT), and C594T (TT) in increasing the risk of NAFLD (all gamma > 1). CONCLUSION: Adiponectin gene promoter -11377C/G (CG), -11377C/G (GG), GPx-1 gene C594T (CT), C594T (TT), and cigarette smoking are risk factors in NAFLD, and the significant association between genetic polymorphisms of -11377C/G, C594T, and cigarette smoking amplify the risk of NAFLD. PMID- 26897100 TI - Image and geometry processing with Oriented and Scalable Map. AB - We turn the Self-organizing Map (SOM) into an Oriented and Scalable Map (OS-Map) by generalizing the neighborhood function and the winner selection. The homogeneous Gaussian neighborhood function is replaced with the matrix exponential. Thus we can specify the orientation either in the map space or in the data space. Moreover, we associate the map's global scale with the locality of winner selection. Our model is suited for a number of graphical applications such as texture/image synthesis, surface parameterization, and solid texture synthesis. OS-Map is more generic and versatile than the task-specific algorithms for these applications. Our work reveals the overlooked strength of SOMs in processing images and geometries. PMID- 26897099 TI - 17q21.31 microdeletion syndrome: Description of a case further contributing to the delineation of Koolen-de Vries syndrome. AB - The widespread use of Array Comparative Genomic Hybridization (aCGH) technology has enabled the identification of several syndromes associated with copy number variants (CNVs) including the 17q21.31 microdeletion. The 17q21.31 microdeletion syndrome, also known as Koolen-de Vries syndrome, was first described in 2006 in individuals with intellectual disabilities and organ abnormalities. We report the clinical, instrumental, cytogenetic and molecular investigations of a boy admitted for epilepsy and intellectual disabilities. We carried out detailed analysis of the clinical phenotype of this patient and investigated the genetic basis by using aCGH. We identified a de novo microdeletion on chromosome 17q21.31, compatible with Koolen-de Vries syndrome. Our case shares some of the typical characteristics of the syndrome already described by other authors: delayed psychomotor development, primarily affecting the expressive language, dysmorphic facial features, and epilepsy. However the clinical outcome was not severe as the intellectual disabilities were moderate with good adaptive and functional behaviour. Epilepsy was easily controlled by a single drug, and he never needed surgery for organ abnormalities. PMID- 26897101 TI - Generalized Safety and Efficacy of Simplified Intravenous Thrombolysis Treatment (SMART) Criteria in Acute Ischemic Stroke: The MULTI SMART Study. AB - BACKGROUND: Common intravenous recombinant tissue plasminogen activator (IV rt PA) exclusion criteria may substantially limit the use of thrombolysis. Preliminary data have shown that the SMART (Simplified Management of Acute stroke using Revised Treatment) criteria greatly expand patient eligibility by reducing thrombolysis exclusions, but they have not been assessed on a large scale. We evaluated the safety and efficacy of general adoption of SMART thrombolysis criteria to a large regional stroke network. METHODS: Retrospective analysis of consecutive patients who received IV thrombolysis within a regional stroke network was performed. Patients were divided into those receiving thrombolysis locally versus at an outside hospital. The primary outcome was modified Rankin Scale score (<=1) at discharge and the main safety outcome was symptomatic intracranial hemorrhage (sICH) rate. RESULTS: There were 539 consecutive patients, and 50.5% received thrombolysis at an outside facility. Ninety percent of the patients possessed common conventional IV rt-PA contraindications. There were no significant differences between local and network treated patients in favorable outcome (45.4% versus 37.4%; odds ratio [OR], .72; P > .09), mortality (9% versus 14%; OR, 1.6; P > .07), or sICH rate (2.6% versus 5.1%; OR, 2.0; P = .13). Multivariate analysis showed no association between receiving IV rt-PA at an outlying spoke hospital and higher rate of sICH or worse outcome at discharge. CONCLUSIONS: Generalized application of SMART criteria is safe and effective. Widespread application of these criteria could substantially increase the proportion of patients who might qualify for treatment. PMID- 26897102 TI - Glycated hemoglobin detection with electrochemical sensing amplified by gold nanoparticles embedded N-doped graphene nanosheet. AB - In the diabetic patients the level of glucose must be determined without any short term fluctuations. The level of Glycated hemoglobin (HbA1c) is accordingly examined for checking diabetes mellitus. HbA1c is considered one of the primarily factor to discern the concentration of average plasma glucose over a long-drawn out period. In our work, we describe a construction of biosensor which is based on fructosyl amino-acid oxidase (FAO) immobilized nitrogen-doped graphene/gold nanoparticles (AuNPs)/fluorine doped tin oxide (FTO) glass electrode. This constructed biosensor exhibits a wide linear range of 0.3 to 2000MUM in response to HbA1c at +0.2V. Consequently, the detection limit of 0.2MUM and good stability (4 months) were achieved. The electrocatalytic activity of this sensor was good as a result of synergistic effect of graphene and AuNPs (2D and 0D nanomaterials). The charge transfer resistance was decreased which was observed by electrochemical impedance spectroscopy (EIS) study. The graphene/AuNPs composites film reveals a distinguished electrochemical response to fructosyl valine (FV) which demonstrates a promising application for electrochemical detection of HbA1c in human blood samples. PMID- 26897103 TI - Paediatric neurological melioidosis: a rehabilitation case report. AB - CONTEXT: Melioidosis is a rare condition, endemic to northern Australia and south east Asia, caused by an infection from the bacteria Burkholderia pseudomallei. The largest epidemiological review to date describes 540 cases of melioidosis seen at Darwin Hospital, in northern Australia, over a 20-year period. Of these, 14 (less than 3%) presented with neurological manifestation, with three deaths. Reports of paediatric cases of melioidosis are rarer. In a review of paediatric cases in northern Australia only eight cases were identified in 10 years. Three of these patients presented with neurological melioidosis, of whom two died in hospital. ISSUES: Whilst the literature refers to prolonged periods of hospitalisation for survivors, the trajectory of functional recovery and process of rehabilitation has not been described. This is a case report describing a 14-year-old boy who presented to a remote medical post with acute neurological symptoms (vomiting, severe headache, ataxia, cranial nerve VI and VII palsy) and was referred to the tertiary paediatric hospital in Perth, Western Australia. Cranial magnetic resonance imaging showed an extensive infiltrative lesion in the posterior fossa and hydrocephalus. Diagnosis of neurological melioidosis required isolation of the pathogen by brain biopsy through sub occipital craniotomy. Medical treatment included surgical management of hydrocephalus, parenteral antibiotic treatment with meropenem and then a prolonged course of oral co-trimoxazole, enteral feeding and tonal management with levodopa-carbidopa and botulinum toxin A injections. Associated neurological signs and symptoms (bradykinesia, tremor, dysphagia, aphasia, hypertonia, exotropia) required intensive rehabilitation to address functional deficits and to promote independence. The purpose of this case report is to document the functional recovery and rehabilitation process of a paediatric case of neurological melioidosis. Knowledge of the recovery pathway is important to add to the understanding of natural history and treatment of this rare disease. LESSONS LEARNED: Occasions of service and functional assessments were recorded prospectively. Inpatient therapy (932 hours, with 934 occasions of service) was delivered across physiotherapy, occupational therapy and speech pathology over 9 months of an inpatient admission. Initial paediatric functional independence measure (WeeFIM) was 18/126, indicating complete dependence in all physical and cognitive domains. Following 9 months of intensive rehabilitation the WeeFIM was 53/126, indicating significant residual disability. This proved to be a challenge for discharge planning back to a remote region of Western Australia. Paediatric neurological melioidosis can lead to significant disability and long-term dependence, despite the provision of lengthy intensive rehabilitation. This case report highlights the challenges and complexity of the rehabilitation services required to optimise outcomes for this patient and achieve a safe discharge to a remote community where limited support services are available. PMID- 26897104 TI - Reply. PMID- 26897106 TI - Zika virus: time to move from case reports to case control. PMID- 26897105 TI - Effect of the introduction of pneumococcal conjugate vaccination on invasive pneumococcal disease in The Gambia: a population-based surveillance study. AB - BACKGROUND: Little information is available about the effect of pneumococcal conjugate vaccines (PCVs) in low-income countries. We measured the effect of these vaccines on invasive pneumococcal disease in The Gambia where the 7-valent vaccine (PCV7) was introduced in August, 2009, followed by the 13-valent vaccine (PCV13) in May, 2011. METHODS: We conducted population-based surveillance for invasive pneumococcal disease in individuals aged 2 months and older who were residents of the Basse Health and Demographic Surveillance System (BHDSS) in the Upper River Region, The Gambia, using standardised criteria to identify and investigate patients. Surveillance was done between May, 2008, and December, 2014. We compared the incidence of invasive pneumococcal disease between baseline (May 12, 2008-May 11, 2010) and after the introduction of PCV13 (Jan 1, 2013-Dec 31, 2014), adjusting for changes in case ascertainment over time. FINDINGS: We investigated 14 650 patients, in whom we identified 320 cases of invasive pneumococcal disease. Compared with baseline, after the introduction of the PCV programme, the incidence of invasive pneumococcal disease decreased by 55% (95% CI 30-71) in the 2-23 months age group, from 253 to 113 per 100 000 population. This decrease was due to an 82% (95% CI 64-91) reduction in serotypes covered by the PCV13 vaccine. In the 2-4 years age group, the incidence of invasive pneumococcal disease decreased by 56% (95% CI 25-75), from 113 to 49 cases per 100 000, with a 68% (95% CI 39-83) reduction in PCV13 serotypes. The incidence of non-PCV13 serotypes in children aged 2-59 months increased by 47% (-21 to 275) from 28 to 41 per 100 000, with a broad range of serotypes. The incidence of non pneumococcal bacteraemia varied little over time. INTERPRETATION: The Gambian PCV programme reduced the incidence of invasive pneumococcal disease in children aged 2-59 months by around 55%. Further surveillance is needed to ascertain the maximum effect of the vaccine in the 2-4 years and older age groups, and to monitor serotype replacement. Low-income and middle-income countries that introduce PCV13 can expect substantial reductions in invasive pneumococcal disease. FUNDING: GAVI's Pneumococcal vaccines Accelerated Development and Introduction Plan (PneumoADIP), Bill & Melinda Gates Foundation, and the UK Medical Research Council. PMID- 26897107 TI - Long-term surveillance of the effect of PCV13: the future challenge in Africa. PMID- 26897108 TI - Detection and sequencing of Zika virus from amniotic fluid of fetuses with microcephaly in Brazil: a case study. AB - BACKGROUND: The incidence of microcephaly in Brazil in 2015 was 20 times higher than in previous years. Congenital microcephaly is associated with genetic factors and several causative agents. Epidemiological data suggest that microcephaly cases in Brazil might be associated with the introduction of Zika virus. We aimed to detect and sequence the Zika virus genome in amniotic fluid samples of two pregnant women in Brazil whose fetuses were diagnosed with microcephaly. METHODS: In this case study, amniotic fluid samples from two pregnant women from the state of Paraiba in Brazil whose fetuses had been diagnosed with microcephaly were obtained, on the recommendation of the Brazilian health authorities, by ultrasound-guided transabdominal amniocentesis at 28 weeks' gestation. The women had presented at 18 weeks' and 10 weeks' gestation, respectively, with clinical manifestations that could have been symptoms of Zika virus infection, including fever, myalgia, and rash. After the amniotic fluid samples were centrifuged, DNA and RNA were extracted from the purified virus particles before the viral genome was identified by quantitative reverse transcription PCR and viral metagenomic next-generation sequencing. Phylogenetic reconstruction and investigation of recombination events were done by comparing the Brazilian Zika virus genome with sequences from other Zika strains and from flaviviruses that occur in similar regions in Brazil. FINDINGS: We detected the Zika virus genome in the amniotic fluid of both pregnant women. The virus was not detected in their urine or serum. Tests for dengue virus, chikungunya virus, Toxoplasma gondii, rubella virus, cytomegalovirus, herpes simplex virus, HIV, Treponema pallidum, and parvovirus B19 were all negative. After sequencing of the complete genome of the Brazilian Zika virus isolated from patient 1, phylogenetic analyses showed that the virus shares 97-100% of its genomic identity with lineages isolated during an outbreak in French Polynesia in 2013, and that in both envelope and NS5 genomic regions, it clustered with sequences from North and South America, southeast Asia, and the Pacific. After assessing the possibility of recombination events between the Zika virus and other flaviviruses, we ruled out the hypothesis that the Brazilian Zika virus genome is a recombinant strain with other mosquito-borne flaviviruses. INTERPRETATION: These findings strengthen the putative association between Zika virus and cases of microcephaly in neonates in Brazil. Moreover, our results suggest that the virus can cross the placental barrier. As a result, Zika virus should be considered as a potential infectious agent for human fetuses. Pathogenesis studies that confirm the tropism of Zika virus for neuronal cells are warranted. FUNDING: Consellho Nacional de Desenvolvimento e Pesquisa (CNPq), Fundacao de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ). PMID- 26897109 TI - Cost-effectiveness of scaling up mass drug administration for the control of soil transmitted helminths: a comparison of cost function and constant costs analyses. AB - BACKGROUND: The coverage of mass drug administration (MDA) for neglected tropical diseases, such as the soil-transmitted helminths (STHs), needs to rapidly expand to meet WHO's 2020 targets. We aimed to compare use of a cost function to take into account economies of scale to the standard method of assuming a constant cost per treatment when investigating the cost and cost-effectiveness of scaling up a STH MDA programme targeting Ascaris lumbricoides. METHODS: We fitted a cost function describing how the costs of MDA change with scale to empirical cost data and incorporated it into a STH transmission model. Using this cost function, we investigated the consequences of taking into account economies of scale on the projected cost-effectiveness of STH control, by comparison with the standard method of assuming a constant cost per treatment. The cost function was fitted to economic cost data collected as part of a school-based deworming programme in Uganda using maximum likelihood methods. We used the model to investigate the total reduction in the overall worm burden, the total number of prevalent infection case-years averted, and the total number of heavy infection case-years averted. For each year, we calculated the effectiveness as the difference between the worm burden or number of cases and the number in absence of treatment. FINDINGS: When using the cost function, the cost-effectiveness of STH control markedly increased as the programme was scaled up. By contrast, the standard method (constant cost per treatment) undervalued this and generated misleading conclusions. For example, when scaling up control in the projected district from 10% to 75% coverage of at-risk school-age children, the cost-effectiveness in terms of prevention of heavy burden infections was projected to increase by over 70% when using the cost function, but decrease by 18% when assuming a constant cost per treatment. INTERPRETATION: The current exclusion of economies of scale in most economic analyses must be addressed if the most cost-effective policies for the control of neglected tropical diseases are to be formulated. These findings are also relevant to other large-scale disease interventions. FUNDING: GlaxoSmithKline, Bill & Melinda Gates Foundation, Partnership for Child Development, and Wellcome Trust. PMID- 26897111 TI - [Death certificate data in France: Production process and main types of analyses]. AB - Mortality data, by the unambiguity of their definition and understanding by all stakeholders, and completeness of registration, are a cornerstone of public health statistics in France and in most industrialized countries. This article describes the data production process, and the main types of possible analyses. Data production is composed of different stages: death certification by a medical doctor on paper or electronic (using a web application) format, data transmission to Inserm, capture and coding of information. The encoding of the information follows the WHO recommendations of the International Classification of Diseases ([ICD], 10th revision used since 2000). It is carried out using an automatic coding software, called Iris, developed in an international consortium. The coding aims, first, at assigning an ICD code to all nosologic entities encountered on the certificate, and then at selecting the underlying cause of death. The latter is the main information used for statistical analyses. Three main types of analysis emerge in the literature: the exploitation of data on the death certificate only, ecological analyses (studies of associations between variables measured across groups) and analysis from data individually linked to other databases. Many public health issues can be addressed with these various analyses. Several developments in the production process are being implemented: the deployment of electronic certification, increased automation of the death certificate information processing and durable and complete record linkage with health insurance and hospitalisation data. They could soon be deeply expanding the scope of possible uses of causes of death data. PMID- 26897110 TI - Consumption of iodized salt may not represent a reliable indicator of iodine adequacy: Evidence from a cross-sectional study on schoolchildren living in an urban area of central Italy. AB - OBJECTIVE: It has been established that iodine prophylaxis prevents endemic goiter. In this study we reported the amount of iodized salt sold by the retailers of Cassino, a city of central Italy. The aim of the study was to evaluate the effects of an iodine prophylaxis program started in 2005 on urinary iodine concentration (UIC) and thyroid volume (TV), and their correlation with anthropometric parameters in a population of schoolchildren. METHODS: The study included 234 schoolchildren (119 girls and 115 boys) ages 13 to 14 y. Each student provided a morning urine sample for UIC determination, and TV was evaluated by ultrasonography. Body weight and height also were measured. Each participant completed a questionnaire reporting the presence of thyroid disease and the consumption of iodized salt and iodine-rich food. RESULTS: The percentage of iodized salt sold by local markets was 42.4%. Median UIC in schoolchildren was 133.9 MUg/L (range 33.2-819.5 MUg/L), with 71 children having mild (range 50.1 99.9 MUg/L) and 10 moderate (range 33.2-48.8 MUg/L) iodine deficiency. Eleven children showed excessive iodine intake (range 300.4-819.5 MUg/L). Median UIC was higher in children using iodized salt or consuming milk. Goiter prevalence was 3.8%. A positive correlation between TV and body weight, height, and surface was observed. CONCLUSIONS: The data reported may suggest the presence of an adequate iodine intake in the population of Cassino despite the low percentage of iodized salt sold by local retailers. This indicates that silent iodine prophylaxis through the consumption of iodine-rich or iodine-enriched food is of importance in the prevention of iodine deficiency disorders. PMID- 26897112 TI - [Lung sarcoidosis: Clinical features and therapeutic issues]. AB - Sarcoidosis is a granulomatous disease of unknown cause. This proteiform disease is characterized by an almost constant and often predominant lung involvement. The natural history of disease is difficult to predict at presentation. Diagnosis is based on a compatible clinical and radiological presentation and evidence of non-caseating granulomas. Exclusion of alternative diseases is also required according to clinical presentation. Biopsy samples of superficial lesions should be considered before other sites like per-endoscopic bronchial biopsies or endobronchial ultrasound-guided transbronchial needle aspiration. Therapeutic strategy for lung disease has to take into account the possible spontaneous resolution observed in newly diagnosed patients. Corticosteroids are the first choice when a treatment is decided, which concerns half of patients. Second and third line therapy are based respectively on immunosuppressive drugs and anti TNFalpha drugs. Sarcoidosis mortality and morbidity are mainly linked to advanced pulmonary sarcoidosis - lung fibrosis, pulmonary hypertension, bronchial stenosis and chronic pulmonary aspergillosis. "Non anti-inflammatory" treatments have to be considered as well. Clinicians have an essential role in treatment indication, end-point targets and evaluation of response to treatment during follow-up and in finding the best benefice to risk balance. Progress made on pharmacogenetics may offer more personalized treatments for the patients. PMID- 26897113 TI - [Digestive neuroendocrine tumors]. AB - Digestive neuroendocrine tumors (NETs) are a group of rare tumors with increasing incidence. Pathological analysis is critical to establish the diagnosis and evaluate tumor grade that relies on differentiation and proliferation index. NETs are mostly diagnosed at an advanced stage because of late occurrence of nonspecific symptoms, and can be associated with hormone hypersecretion. Chromogranin A is the main biochemical marker of NETs. Extension workup relies on conventional imaging (CT-scan, MRI) and isotopic imaging including somatostatin receptor scintigraphy, which should be soon replaced by positron-emitting scintigraphy. The main prognostic factors include tumor stage, metastatic volume, histological differentiation and grade. Hormonal syndromes and poorly differentiated tumors are the two therapeutic emergencies. The treatment of localized well-differentiated tumors relies on endoscopic or surgical resection depending on the location and aggressiveness. Surgical removal is the only potentially curative treatment of metastatic NETs but is rarely feasible and is associated with almost constant relapse. Other antitumor therapies include somatostatin analogs, systemic chemotherapy, liver trans-arterial chemo embolization, targeted therapies and peptide-receptor radionuclide therapy. Management strategy relies on primary tumor location, tumor aggressiveness, metastatic volume and the presence of extra-hepatic metastases. It must take into account the risk of cumulated toxicity in patients whose survival is often prolonged. PMID- 26897114 TI - Effects of zinc on Scots pine (Pinus sylvestris L.) seedlings grown in hydroculture. AB - The 6-week-old seedlings of Scots pine (Pinus sylvestris L.) showed high sensitivity to chronic exposure to zinc in hydroculture, which manifested in a significant inhibition of growth. Changes in the architecture of the root system and the suppression of its growth were shown to be the most striking effects of the toxic effect of zinc. Based on the data relating to the accumulation of zinc predominantly in the root system (by up to 35 times at 300 MUM ZnSO4) and to the reduction in its translocation into the aerial organs, we concluded that P. sylvestris is related to a group of plants that exclude zinc. The seedlings developed a manganese deficiency (revealed by a reduction in Mn content in the roots and needles of up to 3.5 times at 300 MUM ZnSO4) but not an iron deficiency (revealed by an increase in iron content of up to 23.7% in the roots and up to 42.3% in the needles at average). The absence of signs of oxidative stress under the effect of the zinc was detected as evidenced by the reduction in the content of malondialdehyde and 4-hydroxyalkenals in the seedling organs. The leading role of low molecular weight antioxidants in the prevention of oxidative stress in the seedling organs was suggested. Under the influence of zinc, a significant increase in the Trolox Equivalent Antioxidant Capacity of ethanol extracts of the seedling organs was found, which was caused by an increase in the total content of (+)-catechin and proanthocyanidins. PMID- 26897115 TI - Transcriptome-wide identification and expression analysis of chrysanthemum SBP like transcription factors. AB - SQUAMOSA promoter-binding protein (SBP) transcription factors are known to function in a number of processes in plants. Here, we have characterized twelve SBP-like (SPL) genes in the important ornamental species chrysanthemum (Chrysanthemum morifolium). A total of twelve distinct sequences were isolated and amplified based on transcriptomic sequences. Phylogenetic analysis identified two pairs of orthologous proteins for Arabidopsis and chrysanthemum and two pairs of paralogous proteins in chrysanthemum. Conserved motifs in the SPL proteins shared by Arabidopsis and chrysanthemum were scanned using MEME. A bioinformatics analysis revealed that six of these genes contained a miR156 target site, while five CmSPLs were targeted by miR157. Moreover, we used 5' RLM-RACE to map the cleavage sites in CmSPL2 and CmSPL3. The expression of these twelve genes in response to a variety of phytohormone treatments and abiotic stresses was characterized. This work improves our understanding of the various functions of SPL gene family members in the stress response. PMID- 26897116 TI - Organ-specific metabolic responses to drought in Pinus pinaster Ait. AB - Drought is an important driver of plant survival, growth, and distribution. Water deficit affects different pathways of metabolism, depending on plant organ. While previous studies have mainly focused on the metabolic drought response of a single organ, analysis of metabolic differences between organs is essential to achieve an integrated understanding of the whole plant response. In this work, untargeted metabolic profiling was used to examine the response of roots, stems, adult and juvenile needles from Pinus pinaster Ait. full-sib individuals, subjected to a moderate and long lasting drought period. Cyclitols content showed a significant alteration, in response to drought in all organs examined, but other metabolites increased or decreased differentially depending on the analyzed organ. While a high number of flavonoids were only detected in aerial organs, an induction of the glutathione pathway was mainly detected in roots. This result may reflect different antioxidant mechanisms activated in aerial organs and roots. Metabolic changes were more remarkable in roots than in the other organs, highlighting its prominent role in the response to water stress. Significant changes in flavonoids and ascorbate metabolism were also observed between adult and juvenile needles, consistent with previously proven differential functional responses between the two developmental stages. Genetic polymorphisms in candidate genes coding for a Myb1 transcription factor and a malate dehydrogenase (EC 1.1.1.37) were associated with different concentration of phenylalanine, phenylpropanoids and malate, respectively. The results obtained will support further research on metabolites and genes potentially involved in functional mechanisms related to drought tolerance in trees. PMID- 26897117 TI - Identification and validation of reference genes for accurate normalization of real-time quantitative PCR data in kiwifruit. AB - Identification and validation of reference genes are required for the normalization of qPCR data. We studied the expression stability produced by eight primer pairs amplifying four common genes used as references for normalization. Samples representing different tissues, organs and developmental stages in kiwifruit (Actinidia chinensis var. deliciosa (A. Chev.) A. Chev.) were used. A total of 117 kiwifruit samples were divided into five sample sets (mature leaves, axillary buds, stigmatic arms, fruit flesh and seeds). All samples were also analysed as a single set. The expression stability of the candidate primer pairs was tested using three algorithms (geNorm, NormFinder and BestKeeper). The minimum number of reference genes necessary for normalization was also determined. A unique primer pair was selected for amplifying the 18S rRNA gene. The primer pair selected for amplifying the ACTIN gene was different depending on the sample set. 18S 2 and ACT 2 were the candidate primer pairs selected for normalization in the three sample sets (mature leaves, fruit flesh and stigmatic arms). 18S 2 and ACT 3 were the primer pairs selected for normalization in axillary buds. No primer pair could be selected for use as the reference for the seed sample set. The analysis of all samples in a single set did not produce the selection of any stably expressing primer pair. Considering data previously reported in the literature, we validated the selected primer pairs amplifying the FLOWERING LOCUS T gene for use in the normalization of gene expression in kiwifruit. PMID- 26897122 TI - Does atopic dermatitis cause food allergy? A systematic review. AB - BACKGROUND: The association between atopic dermatitis (AD) and food allergy (FA) is not fully understood, although a causal relationship has been suggested. This has important implications for prevention and treatment. OBJECTIVE: We aimed to review the association between AD and FA, the effect of FA on AD severity, chronicity, and age of onset, and the temporal relationship between the two. METHODS: Medline and Embase were systematically searched from inception to November 2014 for studies investigating both AD and FA. RESULTS: Sixty-six studies were identified. Eighteen were population-based, 8 used high-risk cohorts, and the rest comprised patients with either established AD or FA. In population-based studies, the likelihood of food sensitization was up to 6 times higher in patients with AD versus healthy control subjects at 3 months of age (odds ratio, 6.18; 95% CI, 2.94-12.98; P < .001). Other population-based studies reported that up to 53% of subjects with AD were food sensitized, and up to 15% demonstrated signs of FA on challenge. Meanwhile, studies including only patients with established AD have reported food sensitization prevalences up to 66%, with challenge-proven FA prevalences reaching up to 81%. Sixteen studies suggested that FA is associated with a more severe AD phenotype. Six studies indicated that AD of earlier onset or increased persistence is particularly associated with FA. Finally, one study found that AD preceded the development of FA. CONCLUSIONS: This systematic review confirms a strong and dose-dependent association between AD, food sensitization, and FA. AD of increased severity and chronicity is particularly associated with FA. There is also evidence that AD precedes the development of food sensitization and allergy, in keeping with a causal relationship. PMID- 26897123 TI - Mechanical response of cardiovascular stents under vascular dynamic bending. AB - BACKROUND: Currently, the effect of vascular dynamic bending (VDB) has not been fully considered when studying cardiovascular stents' long-term mechanical properties, as the previous studies about stent's mechanical properties mostly focus on the effect of vascular pulsation (VP). More and more clinical reports suggested that the effect of VDB have a significant impact on stent. METHODS: In this paper, an explicit-implicit coupling simulation method was applied to analyze the mechanical responses of cardiovascular stents considering the effect of VDB. The effect of VP on stent mechanical properties was also studied and compared to the effect of VDB. RESULTS: The results showed that the dynamic bending deformation occurred in stents due to the effect of VDB. The effects of VDB and VP resulted in alternating stress states of the stent, while the VDB alternate stresses effective on the stent were almost three times larger than that of the VP. The stress concentration under VDB mainly occurred in bridge struts and the maximal stress was located in the middle loops of the stent. However, the stress distributed uniformly in the stents under the effect of VP. Stent fracture occurred more frequently as a result of VDB with the predicted fracture position located in the bridging struts of the stent. These results are consistent with the reported data in clinical literatures. The stress of the vessel under VDB was higher, than that caused by VP. CONCLUSIONS: The results showed that the effect of VDB has a significant impact on the stent's stress distribution, fatigue performance and overall stress on the vessel, thus it is necessary to be considered when analyzing stent's long-term mechanical properties. Meanwhile, the results showed that the explicit-implicit coupling simulation can be applied to analyze stent mechanical properties. PMID- 26897124 TI - Serum betaine but not choline is inversely associated with breast cancer risk: a case-control study in China. AB - PURPOSE: Choline and betaine are important for DNA methylation and synthesis, and may affect tumor carcinogenesis. To our knowledge, no previous study has examined the association between serum choline and betaine and breast cancer risk. This study aimed to examine whether serum choline and betaine were inversely associated with breast cancer risk among Chinese women. METHODS: This hospital based case-control study consecutively recruited 510 breast cancer cases and 518 frequency-matched (age and residence) controls, and blood samples were available for 500 cases and 500 controls. Serum choline and betaine were assayed by high performance liquid chromatography-tandem mass spectrometry. Multiple unconditional logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs). RESULTS: An inverse association with breast cancer risk was observed for serum betaine (fourth vs first quartile adjusted OR 0.68, 95 % CI 0.47-0.97) and for the ratio of serum betaine to choline (fourth vs first quartile adjusted OR 0.70, 95 % CI 0.48-1.00), but not for serum choline (fourth vs first quartile adjusted OR 0.80, 95 % CI 0.56-1.15). Serum betaine was inversely associated with breast cancer risk in subjects with below-median dietary folate intake (fourth vs first quartile adjusted OR 0.48, 95 % CI 0.30 0.77). CONCLUSIONS: This study suggested that serum betaine but not choline was inversely associated with breast cancer risk. This result needed to be further confirmed by the prospective studies. PMID- 26897126 TI - Induction of nodD Gene in a Betarhizobium Isolate, Cupriavidus sp. of Mimosa pudica, by Root Nodule Phenolic Acids. AB - A range of phenolic acids, viz., p-coumaric acid, 4-hydroxybenzaldehyde, 4 hydroxybenzoic acid, protocatechuic acid, caffeic acid, ferulic acid, and cinnamic acid have been isolated and identified by LC-MS analysis in the roots and root nodules of Mimosa pudica. The effects of identified phenolic acids on the regulation of nodulation (nod) genes have been evaluated in a betarhizobium isolate of M. pudica root nodule. Protocatechuic acid and p-hydroxybenzoic acid were most effective in inducing nod gene, whereas caffeic acid had no significant effect. Phenylalanine ammonia lyase, peroxidase, and polyphenol oxidase activities were estimated, indicating regulation and metabolism of phenolic acids in root nodules. These results showed that nodD gene expression of betarhizobium is regulated by simple phenolic acids such as protocatechuic acid and p hydroxybenzoic acid present in host root nodule and sustains nodule organogenesis. PMID- 26897125 TI - Energy compensation and nutrient displacement following regular consumption of hazelnuts and other energy-dense snack foods in non-obese individuals. AB - PURPOSE: Regular nut consumption reduces cardiovascular disease risk, partly from improvements to dietary quality. Examining how individuals make dietary changes when consuming nuts may reveal key behavioural eating patterns beneficial for the development of dietary interventions. We examined the effects of nuts in comparison with other energy-dense snacks on energy compensation, nutrient displacement, and food group patterns. METHODS: This was a 12-week randomised, controlled, parallel study with four arms: ~1100 kJ/day for each of hazelnuts (42 g), chocolate (50 g), potato crisps (50 g), or no added snack food. Diet records, body composition, and physical activity were measured at baseline and week 12, in 102 non-obese participants. RESULTS: Significant improvements in diet quality were observed in the hazelnut group, particularly when consumed as snacks. Intakes of monounsaturated fat (MUFA) and vitamin E were significantly higher (all P < 0.05), whereas saturated fat and carbohydrate were significantly lower (both P <= 0.022) in the hazelnut group compared to the other groups. Partial energy compensation did not differ significantly between groups, but nutrient displacement values for MUFA and fibre differed significantly. Within the hazelnut group, there was nearly complete displacement for fibre, partial displacement for energy, protein, total fat, MUFA, PUFA, potassium, folate, and vitamin E, and overcompensation for carbohydrate and sugar. CONCLUSIONS: Our results demonstrate that energy compensation occurs for all three intervention snacks in this non-obese population. Regular nut consumption significantly improves nutrient profiles compared to other snacks with changes occurring at the snack level. PMID- 26897127 TI - Pantoea hericii sp. nov., Isolated from the Fruiting Bodies of Hericium erinaceus. AB - Three Gram-negative, facultatively anaerobic bacterial isolates were obtained from the fruiting bodies of the edible mushroom Hericium erinaceus showing symptoms of soft rot disease in Beijing, China. Sequences of partial 16S rRNA gene placed these isolates in the genus Pantoea. Multilocus sequence analysis based on the partial sequences of atpD, gyrB, infB and rpoB revealed P. eucalypti and P. anthophila as their closest phylogenetic relatives and indicated that these isolates constituted a possible novel species. DNA-DNA hybridization studies confirmed the classification of these isolates as a novel species and phenotypic tests allowed for differentiation from the closest phylogenetic neighbours. The name Pantoea hericii sp. nov. [Type strain LMG 28847(T) = CGMCC 1.15224(T) = JZB 2120024(T)] is proposed. PMID- 26897130 TI - Communicating genetic test results within the family: Is it lost in translation? A survey of relatives in the randomized six-step study. AB - Genetic testing for cancer susceptibility genes is increasingly being integrated into medical care. Test results help inform risks of the individual being tested as well as family members who could benefit from knowing the results. The responsibility for informing relatives of genetic test results falls on the proband, the first family member being tested. However, there are several challenges associated with sharing genetic test results within families including incomplete understanding of test results, emotional distance among family members, and poor communication skills. In this paper we describe the communication process between probands randomized to receive BRCA1/2 genetic test results in an enhanced versus a standard of care counseling session, and their first degree relatives with whom they shared results. We contacted 561 first degree relatives of probands who had undergone BRCA1/2 genetic testing to measure their level of understanding of the test results, their difficulty and distress upon hearing the results, the impact of the test results on their risk perception, and their intention to pursue genetic counseling/testing. 82.1 % of relatives correctly reported the test results of their proband. Distress upon hearing the test result was highest for those relatives whose proband received informative test results. Relatives reported a decrease in cancer risk perception after hearing the test results, regardless of the type of result. Intention to pursue counseling/testing was low, even among those relatives whose proband received informative test results. Male relatives were less likely to be informed of test results and more likely to forget hearing them. These results suggest ways to improve the communication process within families. PMID- 26897129 TI - Association of NTproBNP and cTnI with outpatient sudden cardiac death in hemodialysis patients: the Choices for Healthy Outcomes in Caring for ESRD (CHOICE) study. AB - BACKGROUND: Sudden cardiac death (SCD) is the most common etiology of death in hemodialysis patients but not much is known about its risk factors. The goal of our study was to determine the association and risk prediction of SCD by serum N terminal prohormone of brain natriuretic peptide (NTproBNP) troponin I (cTnI) in hemodialysis patients. METHODS: We measured NTproBNP and cTnI in 503 hemodialysis patients of a national prospective cohort study. We determined their association with SCD using Cox regression, adjusting for demographics, co-morbidities, and clinical factors and risk prediction using C-statistic and Net Reclassification Improvement (NRI). RESULTS: Patients' mean age was 58 years and 54 % were male. During follow-up (median 3.5 years), there were 75 outpatient SCD events. In unadjusted and fully-adjusted models, NTproBNP had a significant association with the risk of SCD. Analyzed as a continuous variable, the risk of SCD increased 27 % with each 2-fold increase in NTproBNP (HR, 1.27 per doubling; 95 % CI, 1.13 1.43; p < 0.001). In categorical models, the risk of SCD was 3-fold higher in the highest tertile of NTproBNP (>7,350 pg/mL) compared with the lowest tertile (<1,710 pg/mL; HR for the highest tertile, 3.03; 95 % CI, 1.56-5.89; p = 0.001). Higher cTnI showed a trend towards increased risk of SCD in fully adjusted models, but was not statistically significant (HR, 1.17 per doubling; 95 % CI, 0.98-1.40; p = 0.08). Sensitivity analyses using competing risk models showed similar results. Improvement in risk prediction by adding cardiac biomarkers to conventional risk factors was greater with NTproBNP (C-statistic for 3-year risk: 0.810; 95 % CI, 0.757 to 0.864; and continuous NRI: 0.270; 95 % CI, 0.046 to 0.495) than with cTnI. CONCLUSIONS: NTproBNP is associated with the risk of SCD in hemodialysis patients. Further research is needed to determine if biomarkers measurement can guide SCD risk prevention strategies in dialysis patients. PMID- 26897131 TI - Microbiological profiles of fungal keratitis: a 10-year study at a tertiary referral center. AB - BACKGROUND: Given the rise in cases of fungal keratitis in recent years, this study was performed to better elucidate the microbiological profile, risk factors, and surgical intervention rates of fungal keratitis at a tertiary referral center in the Southeastern USA. FINDINGS: This is a retrospective case series of fungal keratitis infections treated at Duke University Eye Center from January 1, 1998, to October 6, 2008. Of the 4651 culture-proven corneal ulcers identified, 63 (1.4 %) were positive for fungal keratitis with a total of 69 fungal organisms isolated. The majority of isolates were filamentous species (44 of 69, 64 %), and the most commonly isolated organism was Curvularia (11 of 69, 16 %). Bacterial coinfections were found in 24 of the 63 cases (38 %). The most commonly associated risk factors were contact lens wear (n = 15, 24 %) and prior penetrating keratoplasty (PKP) (n = 15, 24 %). Twenty-three cases (37 %) required surgical intervention. The rate of surgical intervention was highest in patients with prior PKP (7/15, 47 %). CONCLUSIONS: In this study, the leading risk factors for fungal keratitis were contact lens wear and prior PKP. Filamentous species were the most common causative pathogens. A relatively high rate of mixed bacterial-fungal infections was found. Patients with prior PKP were more likely to require surgery than patients without history of keratoplasties. PMID- 26897128 TI - Antibiotics Resistance in Rhizobium: Type, Process, Mechanism and Benefit for Agriculture. AB - The use of high-quality rhizobial inoculants on agricultural legumes has contributed substantially to the N economy of farming systems through inputs from biological nitrogen fixation (BNF). Large populations of symbiotically effective rhizobia should be available in the rhizosphere for symbiotic BNF with host plants. The rhizobial populations should also be able to compete and infect host plants. However, the rhizosphere comprises large populations of different microorganisms. Some of these microorganisms naturally produce antibiotics which are lethal to susceptible rhizobial populations in the soil. Therefore, intrinsic resistance to antibiotics is a desirable trait for the rhizobial population. It increases the rhizobia's chances of growth, multiplication and persistence in the soil. With a large population of rhizobia in the soil, infectivity of host plants and the subsequent BNF efficiency can be guaranteed. This review, therefore, puts together findings by various researchers on antibiotic resistance in bacteria with the main emphasis on rhizobia. It describes the different modes of action of different antibiotics, the types of antibiotic resistance exhibited by rhizobia, the mechanisms of acquisition of antibiotic resistance in rhizobia and the levels of tolerance of different rhizobial species to different antibiotics. PMID- 26897132 TI - Response to the Comment on: Common Limb Length Does Not Influence Weight Loss After Standard Laparoscopic Roux-en-Y Gastric Bypass. PMID- 26897133 TI - Pre-clinical evaluation of eight DOTA coupled gastrin-releasing peptide receptor (GRP-R) ligands for in vivo targeting of receptor-expressing tumors. AB - BACKGROUND: Overexpression of the gastrin-releasing peptide receptor (GRP-R) has been documented in several human neoplasms such as breast, prostate, and ovarian cancer. There is growing interest in developing radiolabeled peptide-based ligands toward these receptors for the purpose of in vivo imaging and radionuclide therapy of GRP-R-overexpressing tumors. A number of different peptide sequences, isotopes, and labeling methods have been proposed for this purpose. The aim of this work is to perform a direct side-by-side comparison of different GRP-R binding peptides utilizing a single labeling strategy to identify the most suitable peptide sequence. METHODS: Solid-phase synthesis of eight derivatives (BN1-8) designed based on literature analysis was carried out. Peptides were coupled to the DOTA chelator through a PEG4 spacer at the N terminus. Derivatives were characterized for serum stability, binding affinity on PC-3 human prostate cancer cells, biodistribution in tumor-bearing mice, and gamma camera imaging at 1, 6, and 24 h after injection. RESULTS: Serum stability was quite variable among the different compounds with half-lives ranging from 16 to 400 min at 37 degrees C. All compounds tested showed K d values in the nanomolar range with the exception of BN3 that showed no binding. Biodistribution and imaging studies carried out for compounds BN1, BN4, BN7, and BN8 showed targeting of the GRP-R-positive tumors and the pancreas. The BN8 compound (DOTA PEG-DPhe-Gln-Trp-Ala-Val-NMeGly-His-Sta-Leu-NH2) showed high affinity, the longest serum stability, and the highest target-to-background ratios in biodistribution and imaging experiments among the compounds tested. CONCLUSIONS: Our results indicate that the NMeGly for Gly substitution and the Sta-Leu substitution at the C-terminus confer high serum stability while maintaining high receptor affinity, resulting in biodistribution properties that outperform those of the other peptides. PMID- 26897134 TI - Effect of chronic pesticide exposure on murine cornea: a histopathological, cytological and flow cytometric approach to study ocular damage by xenobiotics. AB - Pesticide exposure can occur directly or indirectly in an occupational setting or otherwise. The health hazards of pesticides have long been studied; however, little is known about the ocular insult of these potent chemicals. In this study, we examined the consequences of long-term pesticide exposure on the ocular tissue in animal model with special focus on the cornea. Swiss Albino mice were sacrificed to obtain the eye globes and various cytological, cytotoxic and histological evaluations, in vitro growth kinetic studies and flow cytometric analyses of select cytokeratins were performed to determine the structural and functional damage due to pesticide exposure. Our study revealed the detrimental impact of this xenobiotic insult by cataloguing the damage to each layer of the cornea wherein it was discovered that all the functional layers as well as the membranes were compromised. We hope that our investigation will pave the way for future studies in this oft overlooked area of affront caused by pesticide exposure to the ocular surface. PMID- 26897138 TI - 53rd National Conference of Indian Academy of Pediatrics 21-24 January 2016, Hyderabad. PMID- 26897136 TI - Comparison of monoplanar versus biplanar medial opening-wedge high tibial osteotomy techniques for preventing lateral cortex fracture. AB - PURPOSE: The purpose of this study was to investigate the mechanical strength of both monoplanar and biplanar medial opening-wedge high tibial osteotomy (MOWHTO) procedures and assess the risk of lateral cortex disruption for both techniques. METHODS: Twelve synthetic tibia models with cortical shells were used as test models. Saw cuts for monoplanar MOWHTO and biplanar MOWHTO were generated on the test models in equal numbers (n = 6 for both groups). Wedge opening load and wedge gap distance were evaluated via compressive tests. RESULTS: The mean gap distance just before the lateral cortex fracture in the monoplanar group was 14.7 +/- 2.9 mm, which was significantly narrower than that in the biplanar group of 19.1 +/- 2.0 mm (p = 0.015). The mean load just before the occurrence of lateral cortex fracture of 32.4 +/- 3.2 N in the monoplanar osteotomy group was significantly lower than that in the biplanar osteotomy group of 111.8 +/- 9.3 N (p = 0.009). CONCLUSION: Performing a MOWHTO via the biplanar rather than the monoplanar technique allows larger-sized wedges to be opened with less risk of lateral cortical fracture. Thus, larger gaps can be opened and higher angle corrections can be achieved using the biplanar osteotomy procedure. From a clinical viewpoint, the biplanar osteotomy technique reduced the risk of lateral cortical hinge fracture during MOWHTO. PMID- 26897137 TI - Similar outcomes of locking compression plating and retrograde intramedullary nailing for periprosthetic supracondylar femoral fractures following total knee arthroplasty: a meta-analysis. AB - PURPOSE: This meta-analysis was designed to compare clinical outcomes, including knee scale score and nonunion rate, of patients with periprosthetic supracondylar fractures of the distal femur after total knee arthroplasty (TKA) who were treated using locking compression plates and retrograde intramedullary nails. METHODS: Studies were included in this meta-analysis if they compared clinical outcomes, including operation time, Knee Society Score (KSS), time to union, nonunion rate, and revision rate due to nonunion, in patients who underwent locking compression plate or retrograde intramedullary nail for periprosthetic distal femur fractures following TKA. RESULTS: Eight studies were included in this meta-analysis. Mean operation time was 11 min shorter (95 % CI -9.56 to 31.33 min; n.s.) and KSS one point higher (95 % CI -8.88 to 11.10; n.s.) with retrograde intramedullary nail than with locking compression plate, but these differences were not statistically significant. The two groups were also similar in mean time to union (0.46 weeks 95 % CI -1.17 to 2.08 weeks; n.s.), the proportion of subjects with nonunion (OR 0.83, 95 % CI 0.26-2.60; n.s.) and the proportion that underwent revision surgery (OR 0.88, 95 % CI 0.32-2.40; n.s.). CONCLUSIONS: Clinical outcomes, including nonunion and revision rates, were similar in patients who underwent locking compression plate and retrograde intramedullary nail fixation for periprosthetic supracondylar femoral fracture following TKA. Orthopaedic surgeons must train to master both the retrograde intramedullary nail and locking compression plate techniques because both approaches can be considered for periprosthetic distal femur fracture after TKA as they have similar clinicoradiologic outcomes. LEVEL OF EVIDENCE: II. PMID- 26897140 TI - Breaking the One Disease One Organism Myth. PMID- 26897135 TI - Cell intrinsic and extrinsic regulation of leukemia cell metabolism. AB - Metabolic homeostasis is a fundamental property of cells that becomes dysregulated in cancer to meet the altered, often heightened, demand for metabolism for increased growth and proliferation. Oncogenic mutations can directly change cellular metabolism in a cell-intrinsic manner, priming cells for malignancy. Additionally, cell-extrinsic cues from the microenvironment, such as hypoxia, nutrient availability, oxidative stress, and crosstalk from surrounding cells can also affect cancer cell metabolism, and produce metabolic heterogeneity within the tumor. Here, we highlight recent findings revealing the complexity and adaptability of leukemia cells to coordinate metabolism. PMID- 26897139 TI - Noise as a Health Hazard for Children, Time to Make a Noise about it. AB - Noise, a modern day curse of advancing infrastructure and technology, has emerged as an important public health problem. Exposure to noise during pregnancy may result in high-frequency hearing loss in newborns, growth retardation, cochlear damage, prematurity and birth defects. Newborns exposed to sound above 45 decibels may experience increase in blood pressure, heart rate, respiratory rate; decreased oxygen saturation; and increased caloric consumption. Noise exposure in older children may result in learning disabilities, attention difficulties, insulin resistance, hypertension, stress ulcers and cardiovascular diseases. Sudden exposure to loud noise can lead to rupture of eardrum. The damaging effects of noise pollution are more noticeable in large metropolitan cities, the hubs of urban settlements and industrial growth. Another concern is noise pollution inside the hospitals (particularly intensive care areas) that can lead to serious health consequences both for caregivers and for children. The issue needs to be addressed by both researchers and policy makers on an urgent basis. PMID- 26897141 TI - Hunting for Mutations in Indian Patients with Hunter Syndrome. PMID- 26897142 TI - Kawasaki Disease in India, Lessons Learnt Over the Last 20 Years. AB - Over the last 20 years, Kawasaki disease is being increasingly recognized in India and it may soon replace acute rheumatic fever to become the commonest cause of acquired heart disease amongst children. However, the vast majority of children with Kawasaki disease in India are still not being diagnosed. Diagnosis of Kawasaki disease is based on a constellation of clinical findings which have a typical temporal sequence. All pediatricians must we familiar with the nuances involved in arriving at a diagnosis of Kawasaki disease. With early diagnosis and prompt treatment, the risk of coronary artery abnormalities can be significantly reduced. PMID- 26897143 TI - Naso-pharyngeal Carriage of Organisms in Children Aged 3-59 months Diagnosed with Severe Community-acquired Pneumonia. AB - OBJECTIVE: To study the naso-pharyngeal carriage of organisms in children diagnosed with severe pneumonia. METHODS: Nasopharyngeal aspirate and swabs for microbiological analyses were collected from 377 children aged 3-59 months with severe pneumonia. RESULTS: 28.6% of the samples were positive for S. pneumoniae, 9.6% were positive for H. influenzae, and 8.5% were positive for both the organisms. Respiratory syncytial virus was detected in 27% of samples. The rate of isolation of S. pneumonia and H. influenzae was significantly more in the age group of 12-59 months. CONCLUSION: In children with severe pneumonia, most common organisms isolated/detected from naso-pharyngeal aspirates were S.pneumoniae and Respiratory Syncytial Virus. PMID- 26897144 TI - Heated Humidified High Flow Nasal Cannula versus Nasal Continuous Positive Airway Pressure as Primary Mode of Respiratory Support for Respiratory Distress in Preterm Infants. AB - OBJECTIVE: To compare the outcomes of preterm infants with respiratory distress initiated on either Heated Humidified High Flow Nasal Cannula or Nasal Continuous Positive Airway Pressure as a primary mode of respiratory support. STUDY DESIGN: Prospective observational cohort study. SETTING: Tertiary care level III neonatal intensive care unit. PARTICIPANTS: 88 preterm infants between 28 to 34 weeks of gestation with mild to moderate respiratory distress within 6 hours of birth. INTERVENTION: Eligible infants were treated either with Heated Humidified High Flow Nasal Cannula (n=46) or Nasal Continuous Positive Airway Pressure (n=42). PRIMARY OUTCOME: Need for mechanical ventilation within 72 hrs of initiating support. RESULTS: Baseline demographic characteristics were comparable between the two groups. There was no difference in the requirement of mechanical ventilation between Heated Humidified High Flow Nasal Cannula (19.5%) and Nasal Continuous Positive Airway Pressure (26.2%) groups [RD-0.74 (95% CI 0.34-1.62; P =0.46)]. Moderate or severe nasal trauma occurred less frequently with Heated Humidified High Flow Nasal Cannula (10.9%) in comparison to Nasal Continuous Positive Airway Pressure (40.5%) (P= 0.004). CONCLUSIONS: Heated Humidified High Flow Nasal Cannula was comparable to Nasal Continuous Positive Airway Pressure as a primary respiratory support for preterm infants with respiratory distress, with lesser incidence of nasal trauma. PMID- 26897145 TI - Hunter Syndrome in Northern India: Clinical features and Mutation Spectrum. AB - OBJECTIVE: To study the clinical profile and mutation spectrum of Hunter syndrome. METHODS: Evaluation of 18 cases of Hunter syndrome from 17 families was done. Mutation analysis of Iduronate sulfatase (IDS) gene was done in 9 families, and mothers of four affected children with no family history. RESULTS: Joint contracture, hepatomegaly and radiological changes were present in all children. 6 (33%) children had normal cognitive function at presentation. Point mutations were identified in all the 9 families for whom mutation analysis was done. Among 4 mothers tested from families without any family history, 2 (50%) were found to be carriers. CONCLUSION: Accurate etiological diagnosis by mutation analysis of IDS gene is important in Hunter syndrome. PMID- 26897146 TI - Blood Pressure-to-Height Ratio as a Screening Tool for Hypertension in Children. AB - OBJECTIVE: To test whether blood pressure-to-height ratio (BPHR) can be used to screen for hypertension in children. METHODS: Data regarding blood pressure and other variables was recorded for 2702 school children between the ages of 10-16 years as a part of a nutritional survey. RESULTS: The optimal thresholds for defining hypertension in boys were 0.76 for systolic BPHR and 0.50 for diastolic BPHR; the respective threshold in girls were 0.80 and 0.52. CONCLUSION: BPHR can be used as an effective screening test for diagnosing both hypertension and prehypertension in children aged 10-16 years. PMID- 26897147 TI - A Writers Dilemma: Where to Publish and Where not to? PMID- 26897149 TI - Placebo-controlled Randomized Trial Evaluating Efficacy of Ondansetron in Children with Diarrhea and Vomiting: Critical Appraisal and Updated Meta analysis: Evidence-based Medicine Viewpoint. PMID- 26897148 TI - Mycoplasma pneumoniae, A Tale of 50 Years. PMID- 26897150 TI - Placebo-controlled Randomized Trial Evaluating Efficacy of Ondansetron in Children with Diarrhea and Vomiting: Critical Appraisal and Updated Meta analysis: Pediatric Gastroenterologists Viewpoint. PMID- 26897151 TI - Placebo-controlled Randomized Trial Evaluating Efficacy of Ondansetron in Children with Diarrhea and Vomiting: Critical Appraisal and Updated Meta analysis: Pediatricians Viewpoint. PMID- 26897152 TI - Airway Diseases Education and Expertise (ADEX ) in Pediatrics: Adaptation for Clinical Practice in India. AB - JUSTIFICATION: Asthma and allergic rhinitis together are part of the concept of one airway, one disease or united airway disease. The management of allergic airway diseases should address this united concept and manage the issue by educating the patients and their parents and health care providers, along with environmental control measures, pharmacotherapy and immunotherapy. Here, we present recommendations from the module of Airway Diseases Education and Expertise (ADEX) that focused on allergic rhinitis, asthma and sleep disorder breathing as a single entity or Allergic Airway Disease. PROCESS: A working committee was formed by the collaboration of Pediatric Allergy Association of India (PAAI) and Indian Academy of Pediatrics (IAP) Allergy and Applied Immunology chapter to develop a training module on united airway disease. OBJECTIVE: To increase awareness, understanding and acceptance of the concept of United Airway disease and to educate the primary health care providers for children and public health officials, in the management of united airway diseases. RECOMMENDATIONS: Recommendations for diagnosis, management and follow up of Allergic airway disease are presented in this document. A better compliance by linking education of child, parent, grandparents and other health care providers, and scientific progress by collaboration between practitioners, academicians, researchers and pharmaceutical companies is suggested. PMID- 26897153 TI - Acquired Toxoplasmosis Presenting with a Brainstem Granuloma in an Immunocompetent Adolescent. AB - BACKGROUND: Toxoplasmosis is an uncommon disease in immunocompetent people. CASE CHARACTERISTICS: We report an adolescent boy with central nervous system toxoplasmosis who presented with progressive lower cranial nerve palsies and a ring-enhancing lesion on neuroimaging. INTERVENTION: Diagnosis of toxoplasmosis was confirmed on histopathology of the excised lesion. MESSAGE: Toxoplasmosis should be considered in the differential diagnosis of focal brain lesions irrespective of immune status. PMID- 26897154 TI - Persistent Atrial Standstill in Acute Myocarditis. AB - BACKGROUND: Atrial standstill manifests as absence of any atrial electrical activity in the surface ECG leads. Persistent atrial standstill secondary to acute myocarditis is extremely rare. CASE REPORT: 10-year-old girl had atrial standstill and heart failure due to acute myocarditis. After recovery from myocarditis, heart failure resolved, but the atrial standstill persisted. OUTCOME: Persistent atrial standstill was treated with permanent pacemaker and anticoagulation. MESSAGE: Acute myocarditis may rarely cause atrial standstill that can last even after recovery from myocarditis. PMID- 26897155 TI - Prevalence of Hypertension Among School Children in a Rural Area of Tamil Nadu. AB - A cross-sectional study was conducted to measure the prevalence of hypertension among 310 rural school children in Tamil Nadu. The prevalence of hypertension and pre-hypertension was 10% and 14.2%, respectively. Prevalence was significantly higher among and private school students. We recommend that children should be screened for hypertension for early diagnosis and prevention of complications. PMID- 26897156 TI - Is Mid-upper Arm Circumference Alone Sufficient to Identify Severe Acute Malnutrition Correctly? AB - Anthropometric data of 2466 children in Haryana revealed low sensitivity (6.9%) and positive predictive value (14.3%) of Mid-upper Arm Circumference (MUAC) at 115 mm cut-off for identifying Severe acute malnutrition (SAM). This raises concerns regarding the reliability of MUAC as a screening tool to identify SAM at the community-level. PMID- 26897157 TI - Effect of Fortification and Additives on Breast Milk Osmolality. AB - This study evaluated the effect of fortification and commonly used additives on the osmolality of human milk. Osmolality after fortification with milk powder and human milk fortifier increased from 303 mOsmol/kg to 397 and 373 mOsmol/kg, respectively. The maximal increase in osmolality was seen with the addition of calcium gluconate. PMID- 26897158 TI - Papaverine for Ischemia Following Peripheral Arterial Catheterization in Neonates. AB - 11 Extremely low birth weight neonates who developed skin discoloration after peripheral arterial catheterization were given intra-arterial papaverine before the removal of arterial line. The skin color turned normal in all these neonates and none developed residual damage. In 3 neonates who could not receive papaverine, one developed gangrene of fingers. PMID- 26897159 TI - Inappropriate Postural Habits of High School Students from the Municipality of Ceres, Brazil. AB - This study aims to evaluate the prevalence of inappropriate postural habits in students. 827 Brazilian students aged 14 to 19 were evaluated with a self administered questionnaire. A high prevalence of (>90%) inappropriate habits in sitting postures (on a chair, to write, and at a computer) and picking up an object off the floor was observed, suggesting the need to develop preventive programs. PMID- 26897160 TI - Oral Paracetamol for Closure of Patent Ductus Arteriosus in Selected Preterm Neonates. AB - We prospectively studied the effect of oral paracetamol in closing hemodynamically significant Patent ductus arteriosus in preterm infants (gestational age <32 weeks) where Ibuprofen was contraindicated. 29 of 40 neonates (72.5%) showed successful response while 11 (29.5%) failed to show any response. No major complications were seen. PMID- 26897161 TI - Immature Platelet Fraction, A Simple and Useful Novel Marker in Dengue Hemorrhagic Fever. PMID- 26897162 TI - Infantile Tremor Syndrome: A Syndrome in Search of its Etiology. PMID- 26897163 TI - Hypervitaminosis D with Dyslipidemia: An Unusual Scenario. PMID- 26897164 TI - Teaching and Assessing Clinical Reasoning Skills. PMID- 26897168 TI - Neuroethics: the pursuit of transforming medical ethics in scientific ethics. AB - Ethical problems resulting from brain research have given rise to a new discipline termed neuroethics, representing a new kind of knowledge capable of discovering the neural basis for universal ethics. The article (1) tries to evaluate the contributions of neuroethics to medical ethics and its suitability to outline the foundations of universal ethics, (2) critically analyses the process of founding this universal ethic. The potential benefits of applying neuroimaging, psychopharmacology and neurotechnology have to be carefully weighed against their potential harm. In view of these questions, an intensive dialogue between neuroscience and the humanities is more necessary than ever. PMID- 26897166 TI - Proposal of a new stage grouping of gastric cancer for TNM classification: International Gastric Cancer Association staging project. AB - BACKGROUND: The current AJCC staging system for gastric cancer (AJCC7) incorporated several major revisions to the previous edition. The T and N categories and the stage groups were newly defined, and adenocarcinoma of the esophagogastric junction (EGJ) was reclassified and staged according to the esophageal system. Studies to validate these changes showed inconsistent results. The International Gastric Cancer Association (IGCA) launched a project to support evidence-based revisions to the next edition of the AJCC staging system. METHODS: Clinical and pathological data on patients who underwent curative gastrectomy at 59 institutions in 15 countries between 2000 and 2004 were retrospectively collected. Patients lost to follow-up within 5 years of surgery were excluded. Patients treated with neoadjuvant therapy were excluded. The data were analyzed in total, and separately by region of treatment. RESULTS: Of 25,411 eligible cases, 84.8 % were submitted from 24 institutions of Japan and Korea, 6.4 % from other Asian countries, and 8.8 % from 29 Western institutions. The T and N categories of AJCC7 clearly stratified the patient survival. Patients with pN3a and pN3b showed distinct prognosis in all regions, and by introducing pN3a and pN3b into a cluster analysis, we established a new stage grouping with better stratification than AJCC7, especially among stage III subgroups. Survival of Siewert type 2 and 3 EGJ tumors was better stratified by this IGCA stage grouping than by either esophageal or gastric scheme of AJCC7. CONCLUSIONS: For the next revision of AJCC classification, we propose a new stage grouping based on a large, worldwide data collection. PMID- 26897169 TI - Collaborative research and the co-production of knowledge for practice: an illustrative case study. AB - BACKGROUND: In 2008, the National Institute for Health Research (NIHR) began funding a major 5-year pilot research programme of translational research in England, establishing nine 'Collaborations for Leadership in Applied Health Research and Care' (CLAHRCs). A number of evaluations were carried out to examine whether or not the various collaborations worked as intended and why. In this paper, we examine what the theory of co-production adds to understanding of processes of knowledge creation and translation we observed in one of the CLAHRCs. METHODS: A case study of a successful knowledge translation project was identified from our wider realist evaluation of the mechanisms of closer collaboration at play in the CLAHRC. In the project, a computer simulation model of an emergency pathway for acute ischaemic stroke was built to explore if and how the time between the onset and treatment of the condition could be minimised by redesigning the pathway. The aim of the case study was to improve our understanding of the nature and workings of the mechanisms of closer collaboration that were associated with the more successful projects by examining the relevance of the theory of co-production. Qualitative methods of analysis were used to explore the fit between the mechanisms of closer collaboration we observed in the realist evaluation and the principles of co-production we identified from the literature. RESULTS: We found a close fit between the nine mechanisms of closer collaboration at work in the project and the principles of co-production (active agents; equality of partners; reciprocity and mutuality; transformative; and facilitated). The successful style of collaborative working exemplified by the project was consistent with a strong form of co-production. CONCLUSIONS: In our view, the theory of co-production provides useful insights into what it is about the qualities of collaborative working that inspire the requisite mechanisms for generating knowledge that is translated into practice. The theory provides a potentially useful basis for future knowledge translation programmes and projects in applied health research in a range of contexts. PMID- 26897165 TI - Constructing an integrated genetic and epigenetic cellular network for whole cellular mechanism using high-throughput next-generation sequencing data. AB - BACKGROUND: Epigenetics has been investigated in cancer initiation, and development, especially, since the appearance of epigenomics. Epigenetics may be defined as the mechanisms that lead to heritable changes in gene function and without affecting the sequence of genome. These mechanisms explain how individuals with the same genotype produce phenotypic differences in response to environmental stimuli. Recently, with the accumulation of high-throughput next generation sequencing (NGS) data, a key goal of systems biology is to construct networks for different cellular levels to explore whole cellular mechanisms. At present, there is no satisfactory method to construct an integrated genetic and epigenetic cellular network (IGECN), which combines NGS omics data with gene regulatory networks (GRNs), microRNAs (miRNAs) regulatory networks, protein protein interaction networks (PPINs), and epigenetic regulatory networks of methylation using high-throughput NGS data. RESULTS: We investigated different kinds of NGS omics data to develop a systems biology method to construct an integrated cellular network based on three coupling models that describe genetic regulatory networks, protein-protein interaction networks, microRNA (miRNA) regulatory networks, and methylation regulation. The proposed method was applied to construct IGECNs of gastric cancer and the human immune response to human immunodeficiency virus (HIV) infection, to elucidate human defense response mechanisms. We successfully constructed an IGECN and validated it by using evidence from literature search. The integration of NGS omics data related to transcription regulation, protein-protein interactions, and miRNA and methylation regulation has more predictive power than independent datasets. We found that dysregulation of MIR7 contributes to the initiation and progression of inflammation-induced gastric cancer; dysregulation of MIR9 contributes to HIV-1 infection to hijack CD4+ T cells through dysfunction of the immune and hormone pathways; dysregulation of MIR139-5p, MIRLET7i, and MIR10a contributes to the HIV 1 integration/replication stage; dysregulation of MIR101, MIR141, and MIR152 contributes to the HIV-1 virus assembly and budding mechanisms; dysregulation of MIR302a contributes to not only microvesicle-mediated transfer of miRNAs but also dysfunction of NF-kappaB signaling pathway in hepatocarcinogenesis. CONCLUSION: The coupling dynamic systems of the whole IGECN can allow us to investigate genetic and epigenetic cellular mechanisms via omics data and big database mining, and are useful for further experiments in the field of systems and synthetic biology. PMID- 26897170 TI - PAR-1 mediated apoptosis of breast cancer cells by V. cholerae hemagglutinin protease. AB - Bacterial toxins have emerged as promising agents in cancer treatment strategy. Hemagglutinin (HAP) protease secreted by Vibrio cholerae induced apoptosis in breast cancer cells and regresses tumor growth in mice model. The success of novel cancer therapies depends on their selectivity for cancer cells with limited toxicity for normal tissues. Increased expression of Protease Activated Receptor 1 (PAR-1) has been reported in different malignant cells. In this study we report that HAP induced activation and over expression of PAR-1 in breast cancer cells (EAC). Immunoprecipitation studies have shown that HAP specifically binds with PAR-1. HAP mediated activation of PAR-1 caused nuclear translocation of p50-p65 and the phosphorylation of p38 which triggered the activation of NFkappaB and MAP kinase signaling pathways. These signaling pathways enhanced the cellular ROS level in malignant cells that induced the intrinsic pathway of cell apoptosis. PAR-1 mediated apoptosis by HAP of malignant breast cells without effecting normal healthy cells in the same environment makes it a good therapeutic agent for treatment of cancer. PMID- 26897171 TI - Injection of Abeta1-40 into hippocampus induced cognitive lesion associated with neuronal apoptosis and multiple gene expressions in the tree shrew. AB - Alzheimer's disease (AD) can incur significant health care costs to the patient, their families, and society; furthermore, effective treatments are limited, as the mechanisms of AD are not fully understood. This study utilized twelve adult male tree shrews (TS), which were randomly divided into PBS and amyloidbetapeptide1-40 (Abeta1-40) groups. AD model was established via an intracerebroventricular (icv) injection of Abeta1-40 after being incubated for 4 days at 37 degrees C. Behavioral, pathophysiological and molecular changes were evaluated by hippocampal-dependent tasks, magnetic resonance imaging (MRI), silver staining, hematoxylin-eosin (HE) staining, TUNEL assay and gene sequencing, respectively. At 4 weeks post-injection, as compared with the PBS group, in Abeta1-40 injected animals: cognitive impairments happened, and the hippocampus had atrophied indicated by MRI findings; meanwhile, HE staining showed the cells of the CA3 and DG were significantly thinner and smaller. The average number of cells in the DG, but not the CA3, was also significantly reduced; furthermore, silver staining revealed neurotic plaques and neurofibrillary tangles (NFTs) in the hippocampi; TUNEL assay showed many cells exhibited apoptosis, which was associated with downregulated BCL-2/BCL-XL associated death promoter (Bad), inhibitor of apoptosis protein (IAP), Cytochrome c (CytC) and upregulated tumor necrosis factor receptor 1 (TNF-R1); lastly, gene sequencing reported a total of 924 mobilized genes, among which 13 of the downregulated and 19 of the upregulated genes were common to the AD pathway. The present study not only established AD models in TS, but also reported on the underlying mechanism involved in neuronal apoptosis associated with multiple gene expression. PMID- 26897172 TI - Transcriptome wide analyses reveal a sustained cellular stress response in the gill tissue of Trematomus bernacchii after acclimation to multiple stressors. AB - BACKGROUND: As global climate change progresses, the Southern Ocean surrounding Antarctica is poised to undergo potentially rapid and substantial changes in temperature and pCO2. To survive in this challenging environment, the highly cold adapted endemic fauna of these waters must demonstrate sufficient plasticity to accommodate these changing conditions or face inexorable decline. Previous studies of notothenioids have focused upon the short-term response to heat stress; and more recently the longer-term physiological response to the combined stress of increasing temperatures and pCO2. This inquiry explores the transcriptomic response of Trematomus bernacchii to increased temperatures and pCO2 at 7, 28 and 56 days, in an attempt to discern the innate plasticity of T. bernacchii available to cope with a changing Southern Ocean. RESULTS: Differential gene expression analysis supported previous research in that T. bernacchii exhibits no inducible heat shock response to stress conditions. However, T. bernacchii did demonstrate a strong stress response to the multi stressor condition in the form of metabolic shifts, DNA damage repair, immune system processes, and activation of apoptotic pathways combined with negative regulation of cell proliferation. This response declined in magnitude over time, but aspects of this response remained detectable throughout the acclimation period. CONCLUSIONS: When exposed to the multi-stressor condition, T. bernacchii demonstrates a cellular stress response that persists for a minimum of 7 days before returning to near basal levels of expression at longer acclimation times. However, subtle changes in expression persist in fish acclimated for 56 days that may significantly affect the fitness T. bernacchii over time. PMID- 26897173 TI - Focal segmental glomerular sclerosis: do not overlook the role of immune response. AB - Focal and segmental glomerular sclerosis (FSGS) is a histological pattern characterized by the partial sclerosis of some, but not all, glomeruli. It may be secondary to diverse etiologies such as mutations of podocyte key genes, loss of nephrons, drugs, and virus infection. However, in most cases of FSGS, the etiology is unknown and these forms are called idiopathic (primary) FSGS. A number of different pathogenic hypotheses have been proposed. The frequent recurrence of nephrotic proteinuria after renal transplantation has attracted the attention to search for plasma factors eventually implicated in the pathogenesis. However a decisive and unifying hypothesis is still lacking. On the other hand, recent findings indicate the involvement of cellular immunity and possibly autoantibodies in the pathogenesis of some forms of FSGS. In this paper we report on the recent advances in the pathophysiology of idiopathic FSGS and suggest the possibility that at least some forms of idiopathic FSGS may be caused by autoimmune reactivity. PMID- 26897175 TI - Comparative speed of kill of sarolaner (Simparica) and afoxolaner (NexGard) against induced infestations of Amblyomma americanum on dogs. AB - BACKGROUND: The lone star tick, Amblyomma americanum, infests dogs and cats in North America and is the vector of the pathogens that cause monocytic and granulocytic ehrlichiosis in dogs and humans. A parasiticide's speed of kill is important to minimize the direct and deleterious effects of tick infestation and especially to reduce the risk of transmission of tick-borne pathogens. In this study, speed of kill of a novel orally administered isoxazoline parasiticide, sarolaner (Simparica chewable tablets), against A. americanum on dogs was evaluated and compared with afoxolaner (NexGard) for 5 weeks following a single oral dose. METHODS: Based on pretreatment tick counts, 24 dogs were randomly allocated to treatment with sarolaner (2 to 4 mg/kg), afoxolaner (2.5 to 6.8 mg/kg) or a placebo. Dogs were examined and live ticks counted at 8, 12, and 24 h after treatment and subsequent re-infestations on Days 7, 14, 21, 28, and 35. Efficacy was determined at each time point relative to counts for placebo dogs. RESULTS: A single oral dose of sarolaner provided 100 % efficacy within 24 h of treatment, and consistently provided >90% efficacy against subsequent weekly re infestations with ticks to Day 28. Significantly more live ticks were recovered from afoxolaner-treated dogs than from sarolaner-treated dogs at 24 h after infestation from Day 7 through Day 35 (P <= 0.0247). At 24 h, efficacy of afoxolaner declined to less than 90% from Day 14 to the end of the study. There were no adverse reactions to treatment. CONCLUSIONS: In this controlled laboratory evaluation, sarolaner had a faster speed of kill against A. americanum ticks than afoxolaner. The rapid and consistent kill of ticks by sarolaner within 24 h after a single oral dose over 28 days, suggests this treatment will provide highly effective and reliable control of ticks over the entire treatment interval, and could help reduce the risk of transmission of tick-borne pathogens by A. americanum. PMID- 26897174 TI - Analysis of tumor-derived DNA in plasma and bone marrow fluid in lung cancer patients. AB - Liquid biopsies such as circulating tumor DNA in plasma and disseminated tumor cells in the bone marrow are currently available. However, it is unclear which types of samples are appropriate for detecting tumor DNA in these biopsies. Here, we collected primary tumors, pulmonary venous blood, peripheral blood, and rib bone marrow fluid from 10 lung cancer patients. Targeted deep sequencing was performed to identify mutations across 70 specimens. As a result, a total of 43 mutations were identified in the primary tumors. The mutation in the tumors was also identified in circulating tumor DNA in the pulmonary venous and peripheral blood in two patients. These patients showed poor prognosis, as compared to the other patients. However, no mutation was identified in the bone marrow in any of the patients. These results demonstrated that circulating tumor DNA in plasma is more sensitive and clinically useful as a biomarker as compared to DNA in bone marrow fluid. PMID- 26897176 TI - Optimal use of external demands in hospitals - a Delphi study from the Netherlands. AB - BACKGROUND: Regulatory authorities focus on promoting compliance of hospitals with a variety of external demands. Due to the amount of these external demands, hospitals might prioritise to cope with the external demands. In this study, we explore to what extent a risk-based prioritisation system developed by one Dutch hospital, is applicable in other hospitals as well. The specific research question was: can a risk-based prioritisation system help hospitals cope with the pressures of external demands? METHODS: We conducted a Delphi study, containing three rounds with seven quality and safety managers. All participants were experienced in coping with external demands in Dutch hospitals in general and their own hospital specifically. These experts were granted access to a sample selection of a database containing about 1500 external demands (January 2014). Prior to the Delphi study, a baseline measurement was carried out, where all participants answered open-ended questions aimed at identifying existing practices, possible challenges concerning external demands and to prepare the survey for the group Delphi study. RESULTS: We identified a high level of consensus during our Delphi research. The experts agreed that at present, Dutch hospitals do not cope with external demands systematically. The participants agreed that the database and the risk-based prioritisation system are useful tools to cope with the amount of external demands and indicated that they would also like to use these tools themselves in the future. CONCLUSIONS: In this study, the participants agreed that the database and the risk-based prioritisation system are both applicable and useful tools to cope with the amount of external demands. Further research addressing the use of the risk-based priority system for specific subsets of external demand is also needed. PMID- 26897177 TI - The anterior midcingulate cortex as a neural node underlying hostility in young adults. AB - Anger typically manifests for only a short period of time, whereas hostility is present for a longer duration. However, both of these emotions are associated with an increased likelihood of psychological problems. The nodes within the neural networks that underlie hostility remain unclear. We presumed that specific nodes might include the anterior midcingulate cortex (aMCC), which seems to be essential for the cognitive aspects of hostility. Thus, the present study first evaluated the associations between regional gray matter density (rGMD) and hostility in 777 healthy young students (433 men and 344 women; 20.7 +/- 1.8 years of age) using magnetic resonance imaging and the hostile behaviors subscale (HBS) of the Coronary-prone Type Scale (CTS) for Japanese populations. The HBS scores were positively correlated with rGMD in the aMCC and in widespread frontal regions from the dorsomedial/dorsolateral prefrontal cortices to the lateral premotor cortex at the whole-brain level. No significant correlation was observed between rGMD and the conjunction of HBS and Trait Anger/Anger-Out scores. Furthermore, no significant interaction effects of sex and HBS scores on rGMD were revealed, although the HBS scores of males were significantly higher than those of females. The present findings indicate that the neural correlates of hostility appear to be more distinct in rGMD than those of anger due to differences and duration. PMID- 26897179 TI - Psychosocial Factors Associated with Subclinical Atherosclerosis in South Asians: The MASALA Study. AB - South Asians have the highest rates of premature atherosclerotic cardiovascular disease amongst all ethnic groups in the world; however this risk cannot be fully explained by traditional risk factors. Participants from the Mediators of Atherosclerosis in South Asians Living in America Study were included in this cross-sectional analysis. The purpose of this study was to investigate the association of psychosocial factors (including anger, anxiety, depressive symptoms, current and chronic stress, and everyday hassles) with carotid intima media thickness (CIMT). Three multivariate models were examined to evaluate the association between the psychosocial factors and CIMT. Findings suggest that the impact of psychosocial factors on subclinical atherosclerosis is differential for South Asian men and women. For men, anxiety and depression were associated; while for women, stress was associated with common carotid intima media thickness, independent of traditional CVD risk factors, diet and physical activity. PMID- 26897181 TI - Adverse Effects of beta-Blocker Therapy on Weight Loss in Response to a Controlled Dietary Regimen. AB - BACKGROUND: The effects of beta-blockers on metabolic parameters including weight loss are poorly understood. METHODS: From a database of 3582 patients who completed The Ottawa Hospital Weight Management Program between 1992 and 2011, a total of 173 patients were receiving beta-blockers and were eligible for the study. We determined differences in rate of weight loss in the first 6 weeks of this 900 kcal/d Optifast (Nestle Health Science, Vevey, Switzerland) meal replacement program for patients treated with beta-blockers compared with (1) matched controls and (2) all participants in the program not being treated with beta-blockers. Secondary outcomes included changes in waist circumference. RESULTS: Mean percent weight loss in the beta-blocker group was reduced compared with the rest of the group (9.7% vs 10.0%; P = 0.0001) as well as with matched controls (9.7% vs 10.3%; P = 0.004). Results were the same after adjusting for prevalent cardiovascular disease (9.7% vs 10.0%; P = 0.006). Similarly, a smaller decrease in waist circumference at 6 weeks was observed in the beta-blocker treated group compared with the rest of the group (-24.2 vs -26.3 cm; P = 0.002) and with matched controls (-24.2 vs -25.2 cm; P = 0.04) and was not altered by adjustment for cardiovascular disease (-24.2 vs 26.3 cm; P = 0.004). CONCLUSIONS: In the absence of a clear medical indication, alternatives to beta-blockers should be considered for the treatment of hypertension in obese individuals. PMID- 26897182 TI - Practical Approaches to Prescribing Physical Activity and Monitoring Exercise Intensity. AB - Regular physical activity helps to prevent heart disease, and reduces the risk of first or subsequent cardiovascular events. It is recommended that Canadian adults accumulate at least 150 minutes of moderate- to vigorous-intensity aerobic exercise per week, in bouts of 10 minutes or more, and perform muscle- and bone strengthening activities at least 2 days per week. Individual exercise prescriptions can be developed using the frequency, intensity, time, and type principles. Increasing evidence suggests that high-intensity interval training is efficacious for a broad spectrum of heart health outcomes. Several practical approaches to prescribing and monitoring exercise intensity exist including: heart rate monitoring, the Borg rating of perceived exertion scale, the Talk Test, and, motion sensors. The Borg rating of perceived exertion scale matches a numerical value to an individual's perception of effort, and can also be used to estimate heart rate. The Talk Test, the level at which simple conversation is possible, can be used to monitor desired levels of moderate- to vigorous intensity exercise. Motion sensors can provide users with practical and useful exercise training information to aid in meeting current exercise recommendations. These approaches can be used by the public, exercise scientists, and clinicians to easily and effectively guide physical activity in a variety of settings. PMID- 26897184 TI - The Society of Thoracic Surgeons National Database: "What's Past Is Prologue". PMID- 26897183 TI - In Your Own Words: Toward a More Perfect Union of Patient Care and Education. AB - Communication with patients and their families is a challenge for busy trainees. It is essential, however, that these trainees learn effective communication skills to create rapport with their patients, to add to their own satisfaction in caring for these patients and to use these conversations to constantly reassess their plans for treating their patients. Reflecting on the plans for and the outcomes of the care of their patients will also significantly enhance the educational value of the participation of trainees in this patient care, while simultaneously improving the care of both their current and their future patients. Finally, gaining facility in elaborating on their plans for and the delivery of patient care will help trainees become more articulate and thoughtful practitioners. PMID- 26897180 TI - The trade-off of availability and growth inhibition through copper for the production of copper-dependent enzymes by Pichia pastoris. AB - BACKGROUND: Copper is an essential chemical element for life as it is a part of prosthetic groups of enzymes including super oxide dismutase and cytochrome c oxidase; however, it is also toxic at high concentrations. Here, we present the trade-off of copper availability and growth inhibition of a common host used for copper-dependent protein production, Pichia pastoris. RESULTS: At copper concentrations ranging from 0.1 mM (6.35 mg/L) to 2 mM (127 mg/L), growth rates of 0.25 h(-1) to 0.16 h(-1) were observed with copper uptake of as high as 20 mgcopper/gCDW. The intracellular copper content was estimated by subtracting the copper adsorbed on the cell wall from the total copper concentration in the biomass. Higher copper concentrations led to stronger cell growth retardation and, at 10 mM (635 mg/L) and above, to growth inhibition. To test the determined copper concentration range for optimal recombinant protein production, a laccase gene from Aspergillus clavatus [EMBL: EAW07265.1] was cloned under the control of the constitutive glyceraldehyde-3-phosphate (GAP) dehydrogenase promoter for expression in P. pastoris. Notably, in the presence of copper, laccase expression improved the specific growth rate of P. pastoris. Although copper concentrations of 0.1 mM and 0.2 mM augmented laccase expression 4 times up to 3 U/mL compared to the control (0.75 U/mL), while higher copper concentrations resulted in reduced laccase production. An intracellular copper content between 1 and 2 mgcopper/gCDW was sufficient for increased laccase activity. The physiology of the yeast could be excluded as a reason for the stop of laccase production at moderate copper concentrations as no flux redistribution could be observed by (13)C-metabolic flux analysis. CONCLUSION: Copper and its pivotal role to sustain cellular functions is noteworthy. However, knowledge on its cellular accumulation, availability and distribution for recombinant protein production is limited. This study attempts to address one such challenge, which revealed the fact that intracellular copper accumulation influenced laccase production and should be considered for high protein expression of copper-dependent enzymes when using P. pastoris. The results are discussed in the context of P. pastoris as a general host for copper -dependent enzyme production. PMID- 26897178 TI - Estrogen- and progesterone-mediated structural neuroplasticity in women: evidence from neuroimaging. AB - There is substantial evidence that the ovarian sex hormones, estrogen and progesterone, which vary considerably over the course of the human female lifetime, contribute to changes in brain structure and function. This structured, quantitative literature reviews aims to summarize neuroimaging literature addressing physiological variation in brain macro- and microstructure across an array of hormonal transitions including the menstrual cycle, use of hormonal contraceptives, pregnancy, and menopause. Twenty-five studies reporting structural neuroimaging of women, addressing variation across hormonal states, were identified from a structured search of PUBMED and were systematically reviewed. Although the studies are heterogenous with regard to methodology, overall the results point to overlapping areas of hormone related effects on brain structure particularly affecting the structures of the limbic system. These findings are in keeping with functional data that point to a role for estrogen and progesterone in mediating emotional processing. PMID- 26897185 TI - How I Teach a Thoracoscopic Lobectomy. PMID- 26897186 TI - The Society of Thoracic Surgeons Congenital Heart Surgery Database: 2016 Update on Outcomes and Quality. AB - The Society of Thoracic Surgeons Congenital Heart Surgery Database is the largest congenital and pediatric cardiac surgical clinical data registry in the world. It is the platform for all activities of The Society of Thoracic Surgeons related to the analysis of outcomes and the improvement of quality in this subspecialty. This article summarizes current aggregate national outcomes in congenital and pediatric cardiac surgery and reviews related activities in the areas of quality measurement, performance improvement, and transparency. The reported data about aggregate national outcomes are exemplified by an analysis of 10 benchmark operations performed from January 2011 to December 2014 and documenting overall discharge mortality (interquartile range among programs with more than 9 cases): off-bypass coarctation, 1.0% (0.0% to 0.9%); ventricular septal defect repair, 0.7% (0.0% to 1.1%); tetralogy of Fallot repair, 1.0% (0.0% to 1.7%); complete atrioventricular canal repair, 3.2% (0.0% to 6.5%); arterial switch operation, 2.7% (0.0% to 5.6%); arterial switch operation plus ventricular septal defect, 5.3% (0.0% to 6.7%); Glenn/hemiFontan, 2.1% (0.0% to 3.8%); Fontan operation, 1.4% (0.0% to 2.4%); truncus arteriosus repair, 9.6% (0.0 % to 11.8%); and Norwood procedure, 15.6% (10.0% to 21.4%). PMID- 26897187 TI - Invited Commentary. PMID- 26897188 TI - Invited Commentary. PMID- 26897190 TI - Invited Commentary. PMID- 26897189 TI - Invited Commentary. PMID- 26897191 TI - Statistical Commentary. PMID- 26897192 TI - Invited Commentary. PMID- 26897193 TI - Invited Commentary. PMID- 26897194 TI - Decreased Hemolysis and Improved Hemodynamic Performance of Synchronized Bileaflet Mechanical Valve. AB - PURPOSE: This study compared the performance of a newly patented synchronized valve (SV) with that of a commercially available (CAV) bileaflet mechanical heart valve. DESCRIPTION: A high-speed camera was used to record the leaflet kinematics of the SV vs the CAV along the flow channel. Transvalvular energy loss, effective orifice area, and hemolysis ratios were obtained using a mock circulatory system at two fixed pulse rates and at various cardiac outputs with a fixed aortic pressure. EVALUATION: The rotational radius and inertia of the SV was lower than that of the CAV during valve closure. For heart rates and at cardiac outputs of 7, 5, and 4 L/min, the ratio of total energy loss to effective energy of the SV was significantly less than the CAV, whereas the effective orifice area of the SV was significantly larger than that of CAV. The hemolysis ratio after 4 hours was significantly higher in the CAV than in the SV for both pulse rates. CONCLUSIONS: The synchronized leaflet motion mitigated leaflet rebound and regurgitation during valve closure, which could decrease energy loss, increase the effective orifice area, and reduce hemolysis. PMID- 26897195 TI - Tamponade Relief by Active Clearance of Chest Tubes. AB - PURPOSE: Chest tubes are used in every case of cardiac surgery to evacuate shed blood from around the heart and lungs. Chest tubes can become partially or totally occluded, leading to tamponade. The purpose of this article is to discuss a novel method of maintaining chest tube patency in the early recovery after cardiothoracic surgery. DESCRIPTION: The PleuraFlow Active Clearance Technology is a system to prevent chest tube clogging that can be used to help routinely maintain chest tube patency at the bedside in the intensive care unit. EVALUATION: A patient exhibited physiologic tamponade that was confirmed by transthoracic echocardiography. The chest tube was successfully reopened by actively clearing the chest tube using Active Clearance Technology, resulting in resolution of the tamponade. CONCLUSIONS: The present study reports the case of a patient with massive postoperative pericardial effusion with tamponade, successfully managed by active clearance chest tube. Further studies will help define the role for this technology in routine cardiac surgery. PMID- 26897196 TI - Invited Commentary. PMID- 26897197 TI - Ventricular Septal Perforation Caused by the Strut of a Mitral Valve Bioprosthesis. AB - Ventricular rupture is a well-known complication of mitral valve replacement. We report a rare complication in which the strut of a recently implanted mitral bioprosthesis eroded through the ventricular septum. We present the strategy of the reoperation in which the sutures holding the repair patch were also used to support the new prosthesis. In addition to ventricular rupture and obstruction of the left ventricular outflow tract by a mitral bioprosthesis, the risk of iatrogenic ventricular septal defect (VSD) should be considered when choosing, sizing, and implanting a mitral bioprosthesis. PMID- 26897198 TI - Venovenous Extracorporeal Membrane Oxygenation With Atrial Septostomy as a Bridge to Lung Transplantation. AB - We report the first successful bridge to lung transplantation using venovenous extracorporeal membrane oxygenation (ECMO) with an atrial septostomy for both pulmonary and right ventricular support. This strategy may provide an alternative to other forms of ECMO support as a bridge to lung transplantation, and potentially allow for ambulation and rehabilitation. PMID- 26897199 TI - Severe Acute Traumatic Mitral Regurgitation, Cardiogenic Shock Secondary to Embolized Polymethylmethracrylate Cement Foreign Body After a Percutaneous Vertebroplasty. AB - We report the case of a 61-year-old woman with acute decompensated heart failure secondary to acute traumatic mitral regurgitation, resulting from polymethylmethacrylate cement found in the left ventricle less than 24 hours after fluoroscopic percutaneous vertebroplasty. The patient had a history of ovarian cancer and had undergone treatment for symptomatic osteoporotic compression fractures of the vertebrae (T11, L1, and L3). The patient underwent a successful emergency open-heart operation, mitral valve replacement, closure of an atrial septal defect, and video-assisted removal of the cement foreign body from the left ventricle. The patient was later discharged with a good outcome. PMID- 26897200 TI - Sapien XT Transcatheter Mitral Valve Replacement Under Direct Vision in the Setting of Significant Mitral Annular Calcification. AB - Mitral valve replacement carries a high risk in patients with extensive mitral annular calcification. We report the case of a 71-year-old woman with severely calcified mitral valve stenosis and extensive annular calcification. We approached the mitral valve through a left atriotomy using cardiopulmonary bypass and cardiac arrest. We successfully deployed a 29-mm Sapien XT valve under direct visualization with satisfactory positioning. We further balloon-expanded the device to diminish the likelihood of periprosthetic regurgitation. Open mitral valve replacement with a transcatheter valve can be performed without the need for decalcification of the mitral annulus and is a good alternative to conventional mitral valve replacement. PMID- 26897201 TI - A Cranial-Sided Approach for Repeated Mitral Periprosthetic Leak After Right Pneumonectomy. AB - A 72-year-old man presented with worsening dyspnea on effort. He underwent right pneumonectomy 40 years ago, then mitral valve replacement through a right thoracotomy 8 years ago with repeat surgery to repair a periprosthetic valve leak; the mediastinum was displaced to the right, and the heart was rotated counterclockwise. Transthoracic echocardiography showed periprosthetic valve leak recurrence near the left atrial appendage. We repaired the periprosthetic valve leak through a median sternotomy. Transecting the main pulmonary artery allowed us to widely open the cranial-sided left atrium. We obtained good exposure of the mitral valve, and repaired the periprosthetic valve leak using pledgeted sutures and a pericardial patch. PMID- 26897202 TI - A Rare Case of Plastic Bronchitis in an Adult Patient After Cardiopulmonary Bypass. AB - Plastic bronchitis is a rare life-threatening complication observed after cardiopulmonary bypass (CPB). We describe a case of a 54-year-old man in whom a fulminant case of plastic bronchitis developed after coronary artery bypass grafting (CABG) and mitral valve repair. A brief review of the literature is also presented. PMID- 26897203 TI - Normally Functioning Cooley-Cutter Mechanical Prosthesis Associated With Ascending Aorta Aneurysm 39 Years After Implantation. AB - The Cooley-Cutter prosthesis is a caged-disc mechanical heart valve introduced by Dr Cooley in the 1960s. Although the valve has been implanted worldwide in more than 3,000 patients, there is a lack of detailed data on its long-term performance, only anecdotal reports. We report the case of a patient who had undergone aortic valve replacement with a Cooley-Cutter prosthesis 39 years earlier for rheumatic disease on a tricuspid aortic valve and in whom a proximal aortic aneurysm had subsequently developed. PMID- 26897204 TI - Aortic Valve Leaflet Perforation After Minimally Invasive Mitral Valve Repair. AB - We report on 3 consecutive patients who suffered significant aortic leaflet injury during minimally invasive mitral valve reconstruction procedures and who subsequently underwent reoperation in our institution. In all cases, aortic valves were preserved, and the perforated leaflets were repaired using autologous pericardial patches. PMID- 26897205 TI - Postoperative Migration of an Edwards-SAPIEN XT Mitral Valve-in-Valve Treated With Direct Vision Implantation During Beating-Heart Bypass. AB - Transcatheter valve-in-valve mitral valve replacement provides treatment options to high-risk patients but is subject to its own complications. We present the migration of a transcatheter balloon-expandable Edwards-SAPIEN XT valve (Edwards Lifesciences, Irvine, CA) within a previously implanted surgical Carpentier Edwards valve (Edwards Lifesciences) and our novel approach to its treatment. PMID- 26897206 TI - Total Aortic Replacement for a 9-Year-Old Boy With Loeys-Dietz Syndrome. AB - Loeys-Dietz syndrome (LDS) is a recently identified rare connective tissue disorder caused by mutations of the transforming growth factor-beta receptors and first described in 2005. It is an autosomal dominant syndrome with 2 different phenotypic expressions-LDS I and II. LDS is characterized by the triad of arterial tortuosity and aneurysm, hypertelorism, and a bifid uvula or cleft palate. We present a case of a 9-year-old boy diagnosed with LDS who underwent urgent thoracoabdominal aortic aneurysm repair followed by total arch replacement and aortic valve-sparing root replacement (AVSRR). PMID- 26897207 TI - Tricuspid Atresia IIc With a Vascular Ring: Novel Approach for Fontan Completion. AB - We report a successful Fontan completion in a 22-month-old boy with tricuspid atresia (TA) IIc with a vascular ring. The patient was referred at 1 month of age and was diagnosed with TA IIc using echocardiography. Subsequent 3-dimensional computed tomography revealed a vascular ring. We describe a reconstructive approach for such a heart defect, involving a Damus-Kaye-Stansel (DKS) anastomosis reduction plasty combined with a bidirectional cavopulmonary shunt (BCPS) created by end-to-end suturing of the right superior vena cava (SVC) to the left central pulmonary artery (PA), called the SVC translocation technique. PMID- 26897208 TI - Two Cases of Ventriculocoronary Connection From the Left Ventricle in Hypoplastic Left Heart Syndrome. AB - Advanced surgical technique and comprehensive postoperative management have improved remarkably early and late outcomes of hypoplastic left heart syndrome. However, recent reports have focused on the poor outcome in a series of cases with mitral stenosis and aortic atresia subtype, and ventriculocoronary connections. We consider treatment strategies by reviewing 2 cases of ventriculocoronary connection, both of which had poor outcomes. PMID- 26897209 TI - Aortic and Pulmonary Root Aneurysms in a Child With Loeys-Dietz Syndrome. AB - We report the case of an 11-year-old boy with Loeys-Dietz syndrome, with both aortic and pulmonary aneurysms requiring cardiac operation because of progressive valve incompetence resulting from loss of coaptation of the cusps. Arterial medial changes, consisting of disarray of elastic fibers and increased collagen deposition, were observed in surgical specimens from both the aorta and the pulmonary artery of our patient, and the strong pSmad2 nuclear staining of smooth muscle cells of both aortic and pulmonary tunica media are the best evidence of transforming growth factor-beta pathway activation in Loeys-Dietz syndrome. PMID- 26897210 TI - Surgical Treatment of Hepatic Hydrothorax: A "Four-Step Approach". AB - Recently, various video-assisted thoracoscopic surgical techniques have been reported with occasional success in treating hepatic hydrothorax (HH). In 2 patients with refractory HH, we applied a combination of four therapeutic modalities as a single procedure named as a "four-step approach": (1) pneumoperitoneum for localization of diaphragmatic defects, (2) thoracoscopic pleurodesis, (3) postoperative continuous positive airway pressure, and (4) drainage of ascites for abdominal decompression. The treatment was successful in both patients, without recurrence during the follow-up period of 24 and 3 months, respectively. PMID- 26897211 TI - Pulmonary Vein Pseudoaneurysm Secondary to Blunt Trauma: A Novel Management Strategy. AB - Traumatic pulmonary vein pseudoaneurysm is an extremely rare condition that is challenging to manage. We present a unique case of a pulmonary vein pseudoaneurysm from blunt trauma in a patient with previous ipsilateral decortication. The patient was treated with percutaneous transparenchymal access to the pulmonary vein pseudoaneurysm. PMID- 26897212 TI - Multiple-Modality Imaging of Giant Coronary Artery Aneurysms in Kawasaki Disease. PMID- 26897213 TI - Single-Incision Thoracoabdominal Approach With Normothermic Cardiopulmonary Bypass for the Management of Urologic Tumors Invading the Inferior Vena Cava. AB - Urologic tumors invading the inferior vena cava can be a difficult management problem. They are traditionally dealt with utilizing hypothermic circulatory arrest through central cannulation for cardiopulmonary bypass performed through a median sternotomy in addition to the large abdominal incision for the kidney tumor. We describe a single incision approach utilizing normothermic cardiopulmonary bypass to address this technical challenge. PMID- 26897214 TI - Secondary Reverse Slide Tracheoplasty for Airway Rescue. AB - Slide tracheoplasty is used in cases of tracheal stenosis or injury. With expanding indications for its use at tertiary centers, salvage techniques for dehiscence or restenosis after slide tracheoplasty are increasingly relevant. We present a case in which slide tracheoplasty was augmented with an anterior costochondral graft that stenosed again and ultimately failed. We salvaged this airway emergency by performing a secondary reverse slide tracheoplasty. Using this technique, we were able to establish a safe and durable airway using only native airway tissue. PMID- 26897215 TI - Double-Switch Repair of Corrected Transposition in Association With Criss-Cross Atrial Morphology. AB - Corrected transposition is a relatively uncommon congenital heart defect characterized by discordance at both the atrioventricular and ventriculoarterial levels. A rare subset of patients with corrected transposition also have criss cross atrial morphology. We report the surgical treatment of 2 patients with corrected transposition in association with criss-cross atrial morphology, emphasizing the novel atrial baffle required for this operation. PMID- 26897216 TI - Simplified Method for Treating Osteomyelitis of the Sternoclavicular Joint. AB - Osteomyelitis of the sternoclavicular joint is a rare yet challenging problem. It is commonly treated by resection and a muscle flap. We report a case that was treated with single-stage resection of both the sternoclavicular joint and part of the sternum followed by implantation of calcium sulfate beads impregnated with antibiotics and primary closure without a muscle flap. A single-stage debridement with resection for osteomyelitis of the sternoclavicular joint and primary closure with calcium sulfate beads impregnated with antibiotics may be an option when dealing with this difficult clinical problem. PMID- 26897217 TI - Reply. PMID- 26897218 TI - Limitations of Direct Regional Spinal Cord Monitoring Using Near-Infrared Spectroscopy: Indirect Paraspinal Collateral Network Surveillance Is the Answer! PMID- 26897219 TI - Azygous Vein Flap Is a Good Alternative for Bronchial Stump Reinforcement. PMID- 26897220 TI - Reply. PMID- 26897221 TI - Tailoring the Surgical Procedure Is a Delicate Process to Have Optimal Gain From the Surgery. PMID- 26897222 TI - Reply. PMID- 26897223 TI - Tumor Size, Margin Distance Rate, and Margin Cytologic Results Influence Recurrence and Survival After Wedge Resection for Lung Cancer. PMID- 26897224 TI - Videothoracoscopy for Pulmonary Hydatidosis. PMID- 26897225 TI - Reply. PMID- 26897226 TI - What Is a True Risk Factor for Mortality After Coronary Artery Bypass Grafting? PMID- 26897227 TI - Reply. PMID- 26897228 TI - Reply. PMID- 26897229 TI - Pulmonary Artery Band as Bridge to Ventricular Assist Device by Preconditioning of the Right Ventricle. PMID- 26897230 TI - Impact of Legislation, Guidelines and Practice on BIMA. PMID- 26897231 TI - Giant Left Ventricular Myxoma With Obstruction of the Left Ventricular Outflow Tract. AB - A rare case of giant left ventricular (LV) myxoma with obstruction of the left ventricular outflow tract (LVOT) was found incidentally on echocardiography in an asymptomatic 21-year-old woman. The tumor was successfully resected through transatrial septal access. PMID- 26897232 TI - Complex Surgical Repair of a Flail Tricuspid Valve After Chest Wall Trauma in a Pediatric Patient. AB - Traumatic injury to the tricuspid valve can result from severe nonpenetrating chest wall trauma. We present the case of an initially asymptomatic 11-year-old girl who was kicked in the chest by a horse. The trauma resulted in avulsed papillary muscles, ruptured chordae, and right heart failure. She underwent early tricuspid valve reconstruction and annuloplasty. We advocate for routine use of echocardiography to assess for traumatic injury to intracardiac structures. In addition, we believe that early surgical intervention may prevent right-sided heart dysfunction, atrial arrhythmias, and the need for valve replacement. PMID- 26897233 TI - Bentall Operation in a Patient With Severe Hemophilia A and Marfan Syndrome by Use of a Biologic Composite Graft. AB - We describe a patient with severe hemophilia A and Marfan syndrome who underwent an elective Bentall operation. Because of the severe hemophilia, anticoagulation could not be given postoperatively; thus, a biologic Valsalva conduit graft was used. During the procedure, factor VIII was given as a bolus dose just before incision, then by continous infusion intraoperatively to maintain the factor VIII activity level between 200% and 300%. Minimal postoperative bleeding occurred. The infusion was continued postoperatively at a lower dose until all chest tubes, pacing wires, and invasive catheters were removed. The patient was discharged on postoperative day 7 without adverse events. PMID- 26897234 TI - Perioperative Extracorporeal Membrane Oxygenation to Facilitate Lung Resection After Contralateral Pneumonectomy. AB - A 75-year-old man previously underwent pneumonectomy for lung cancer. He subsequently had colorectal adenocarcinoma, and resection of metastases from his remaining lung was performed. Venovenous extracorporeal membrane oxygenation was used for perioperative respiratory support to facilitate intraoperative deflation of the remaining lung and optimization of the surgical field. Venovenous extracorporeal membrane oxygenation was continued postoperatively, allowing immediate extubation, thus avoiding strain on suture lines. Advantages, and potential risks, of venovenous extracorporeal membrane oxygenation for thoracic surgery are discussed. PMID- 26897235 TI - Native Mitral Stenosis Treated With Transcatheter Mitral Valve Replacement. AB - Surgical treatment of mitral stenosis with extreme calcification remains a challenge. Recently, the balloon-expandable valve prosthesis, anchored by radial force, offers a new option for these patients. We present 2 cases of transcatheter mitral valve replacement in patients with severe native mitral valve stenosis and annular calcification deemed too extensive for conventional surgical techniques. PMID- 26897236 TI - A Thoracotomy Approach for the Surgical Repair of a Left Ventricular Free Wall Rupture. AB - In the current era of rapid culprit vessel revascularization in acute myocardial infarction, ventricular free wall rupture is becoming increasingly uncommon. In rare cases adherent pericardium may contain this rupture, creating a temporary stable pseudoaneurysm. With the aid of intraoperative pictures, we describe herein a left thoracotomy approach for the surgical correction of a left ventricular pseudoaneurysm secondary to free wall rupture. PMID- 26897237 TI - High-Intensity Transient Signals in the Outflow Graft and Thrombosis of a HeartWare Left Ventricular Assist Device. AB - We report the echocardiographic detection of microbubbles in the outflow prosthesis of a HeartWare HVAD left ventricular assist device using transthoracic echocardiography. In this case it was a specific sign associated with device thrombosis that resolved after successful treatment with systemic thrombolysis. PMID- 26897238 TI - Atypical Sign of Contained Rupture of Valsalva Sinus After Repair of Aortic Dissection: Submammary Hematoma. PMID- 26897240 TI - Bilateral Thoracoscopic Splanchnotomy to Alleviate Pain in Chronic Pancreatic Disease. AB - Chronic intractable pain is a common problem in severe pancreatic disease. Bilateral thoracoscopic splanchnotomy, a thoracoscopic neurotomy of the splanchnic nerves, is rarely performed but may provide significant pain relief in these patients. We present a safe strategy that uses prone positioning and two thoracoscopic ports for either hemithorax, permitting easy exposure and simple dissection of the greater and lesser splanchnic nerves. In our experience, this technique provides excellent pain relief with a minimal postoperative stay and few postoperative adverse events. This intervention has the potential to reduce dependency on opioid agents and improve quality of life in carefully selected patients. PMID- 26897239 TI - Congenital Bronchial Artery to Pulmonary Artery Fistula in a Patient With Lung Cancer Involving the Carina. PMID- 26897241 TI - Spotlight on esophageal perforation: A multinational study using the Pittsburgh esophageal perforation severity scoring system. AB - OBJECTIVE: The Pittsburgh group has suggested a perforation severity score (PSS) for better decision making in the management of esophageal perforation. Our study aim was to determine whether the PSS can be used to stratify patients with esophageal perforation into distinct subgroups with differential outcomes in an independent study population. METHODS: In a retrospective study cases of esophageal perforation were collected (study-period, 1990-2014). The PSS was analyzed using logistic regression as a continuous variable and stratified into low, intermediate, and high score groups. RESULTS: Data for 288 patients (mean age, 59.9 years) presenting with esophageal perforation (during the period 1990 2014) were abstracted. Etiology was spontaneous (Boerhaave; n = 119), iatrogenic (instrumentation; n = 85), and traumatic perforation (n = 84). Forty-three patients had coexisting esophageal cancer. The mean PSS was 5.82, and was significantly higher in patients with fatal outcome (n = 57; 19.8%; mean PSS, 9.79 vs 4.84; P < .001). Mean PSS was also significantly higher in patients receiving operative management (n = 200; 69%; mean PSS, 6.44 vs 4.40; P < .001). Using the Pittsburgh strata, patients were assigned to low PSS (<=2; n = 63), intermediate PSS (3-5; n = 86), and high PSS (>5; n = 120) groups. Perforation related morbidity, length of stay, frequency of operative treatment, and mortality increased with increasing PSS strata. Patients with high PSS were 3.37 times more likely to have operative management compared with low PSS. CONCLUSIONS: The Pittsburgh PSS reliably reflects the seriousness of esophageal perforation and stratifies patients into low-, intermediate-, and high-risk groups with differential morbidity and mortality outcomes. PMID- 26897243 TI - Discussion. PMID- 26897242 TI - Comparison of outcomes for patients with lepidic pulmonary adenocarcinoma defined by 2 staging systems: A North American experience. AB - OBJECTIVE: Application of the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification of lepidic adenocarcinomas in conjunction with American Joint Committee on Cancer (AJCC) staging has been challenging. We aimed to compare IASLC/ATS/ERS and AJCC classifications, to determine if they could be integrated as a single staging system. METHODS: We reviewed patients from 2001-2013 who had AJCC stage I lepidic adenocarcinomas, and categorized them according to IASLC/ATS/ERS guidelines: adenocarcinoma in situ (AIS); minimally invasive adenocarcinoma (MIA); or invasive adenocarcinoma (IA). We integrated the 2 classification systems by separating AIS and MIA as being stage 0, and routinely classifying IA as stage I. RESULTS: Median follow-up was 52 months in 138 patients. The IASLC/ATS/ERS classification demonstrated a higher disease-free survival (DFS) in AIS (100%) and MIA (96%) versus IA (80%) (P = .022), and higher overall survival (OS): 100% for AIS and MIA, versus 90% for IA (P = .049). The AJCC classification identified a DFS of 87% and an OS of 94% for stage I patients. Integration of the 2 systems demonstrated higher DFS in stage 0 (98%) versus I (80%) (P = .006), and higher OS: 100% for stage 0 versus 90% for stage I (P = .014). CONCLUSIONS: The IASLC/ATS/ERS classification better discriminates AIS and MIA compared with current AJCC staging; however, integration suggests that these categories may be collectively classified in AJCC staging, based on similarly favorable outcomes and distinctive survival rates. PMID- 26897244 TI - The total artificial heart in pediatrics: Expanding the repertoire. PMID- 26897245 TI - Antimicrobial drug use and risk factors associated with treatment incidence and mortality in Swiss veal calves reared under improved welfare conditions. AB - Ninety-one Swiss veal farms producing under a label with improved welfare standards were visited between August and December 2014 to investigate risk factors related to antimicrobial drug use and mortality. All herds consisted of own and purchased calves, with a median of 77.4% of purchased calves. The calves' mean age was 29+/-15days at purchasing and the fattening period lasted at average 120+/-28 days. The mean carcass weight was 125+/-12kg. A mean of 58+/-33 calves were fattened per farm and year, and purchased calves were bought from a mean of 20+/-17 farms of origin. Antimicrobial drug treatment incidence was calculated with the defined daily dose methodology. The mean treatment incidence (TIADD) was 21+/-15 daily doses per calf and year. The mean mortality risk was 4.1%, calves died at a mean age of 94+/-50 days, and the main causes of death were bovine respiratory disease (BRD, 50%) and gastro-intestinal disease (33%). Two multivariable models were constructed, for antimicrobial drug treatment incidence (53 farms) and mortality (91 farms). No quarantine, shared air space for several groups of calves, and no clinical examination upon arrival at the farm were associated with increased antimicrobial treatment incidence. Maximum group size and weight differences >100kg within a group were associated with increased mortality risk, while vaccination and beef breed were associated with decreased mortality risk. The majority of antimicrobial treatments (84.6%) were given as group treatments with oral powder fed through an automatic milk feeding system. Combination products containing chlortetracycline with tylosin and sulfadimidine or with spiramycin were used for 54.9%, and amoxicillin for 43.7% of the oral group treatments. The main indication for individual treatment was BRD (73%). The mean age at the time of treatment was 51 days, corresponding to an estimated weight of 80-100kg. Individual treatments were mainly applied through injections (88.5%), and included administration of fluoroquinolones in 38.3%, penicillines (amoxicillin or benzylpenicillin) in 25.6%, macrolides in 13.1%, tetracyclines in 12.0%, 3th and 4th generation cephalosporines in 4.7%, and florfenicol in 3.9% of the cases. The present study allowed for identifying risk factors for increased antimicrobial drug treatment and mortality. This is an important basis for future studies aiming at reducing treatment incidence and mortality in veal farms. Our results indicate that improvement is needed in the selection of drugs for the treatment of veal calves according to the principles of prudent use of antibiotics. PMID- 26897246 TI - A cross sectional study evaluating the prevalence of Coxiella burnetii, potential risk factors for infection, and agreement between diagnostic methods in goats in Indiana. AB - Coxiella burnetii is the etiologic agent of the zoonotic disease Q fever and is considered to be endemic in domestic ruminants. Small ruminants in particular are important reservoirs for human infection. Serologic and molecular methods are both available for diagnosis of infection with C. burnetii, but there has been little research evaluating the prevalence of this organism in small ruminants outside of the context of clinical disease outbreaks. The objectives of this study were to estimate seroprevalence of C. burnetii and the prevalence of shedding of C. burnetii DNA in milk by goats in Indiana, USA, to evaluate potential risk factors for association with C. burnetii exposure and shedding, and to assess the level of agreement between the enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (PCR) tests used to estimate prevalence. A total of 649 does over 1 year of age and not pregnant at the time of sampling were included in the study. Serum samples were collected from 608 does representing 89 farms. Milk samples were collected from 387 does representing 85 farms. Both milk and serum samples were collected from 356 does representing 80 farms. The estimated individual seroprevalence and shedding prevalence in milk adjusted for clustering were 3.1% (n=23/608, 95% CI: 1.2-7.0%) and 2.5% (n=9/387, 9.5% CI: 1.0-5.6%) respectively. Estimated adjusted herd level C. burnetii seroprevalence and herd level shedding prevalence were 11.5% (n=10/89, 95% CI: 6.4-20.1%) and 7.0% (n=6/85, 95% CI: 3.3-14.6%) respectively. Based on a generalized estimating equation model (GEE), meat breeds of goat had 7.0 times increased odds of shedding C. burnetii DNA in milk samples as compared to dairy breeds. Agreement between tests as determined by Cohen's kappa was poor at both the individual (kappa=0.04, 95% CI: -0.1 to 0.2) and herd (kappa=0.2, 95% CI: -0.1 to 0.5) levels. This indicates that serologic screening alone is unlikely to prevent the introduction of does shedding C. burnetii into herds. PMID- 26897247 TI - The performance measurement-management divide in public health. AB - What happens when performance measurement and management (PMM) is applied to public health systems? This review of the experiences of high-income jurisdictions reveals considerable challenges, some familiar from the general public management literature and some more unique to public health. To aid understanding, the PMM ladder, a framework for evaluating PMM systems is developed and applied to 55 public health measurement systems from Australia, Canada, EU, New Zealand, UK and US. Results indicate that: considerable measurement is occurring for informational purposes; measurement focuses more on clinical than on population health measures; and there is relatively little use of measurement results for improving management. Results demonstrate that much public health performance measurement is restricted to population health outcomes and fails to include more proximate activity and output measures that would be more useful for managing public health organizations. There are early signs of the emergence of a new breed of public health performance measurement that attempts to do just this. The PMM ladder proved useful for assessing efforts across a range of jurisdictions. It allows policymakers and managers to easily compare their PMM efforts with others and assists researchers in assessing what happens when PMM is applied to public health. PMID- 26897249 TI - Centralization of pancreatoduodenectomy a decade later: Impact of the volume outcome relationship. AB - BACKGROUND: The hospital volume-outcome relationship for complex procedures has led to the suggestion that care should be centralized. This study was performed to investigate whether centralization is occurring for pancreatoduodenectomy (PD) and to examine its effect on short-term postoperative outcomes. METHODS: We queried the New York State Statewide Planning and Research Cooperative System database (n = 6,185, 2002-2011) and the California and Florida State Inpatient Databases (n = 6,766 and 4,810, respectively, 2002-2011) for PD. Hospitals were divided into low (<=10), medium (11-25), high (25-60), and very high (>=61) groups depending on annual volume. Hierarchical logistic modeling accounted for patient clustering within hospitals. RESULTS: A migration of cases from low volume to medium, high, and very high-volume (MHVH) hospitals occurred in these 3 states (P < .01). There was an increase in the number of MHVH hospitals and a decrease in the number of low-volume hospitals performing PD across all states over time, with a large number of hospitals ceasing to perform PD cases entirely. Comorbidities such as congestive heart failure and diabetes were more prevalent in low-volume hospitals. After we adjusted for all predictors, MHVH hospitals had less rates of mortality and morbidity and shorter durations of stay than low volume hospitals (P < .05); 30-day readmission rates were similar across all volume groups. CONCLUSION: Centralization of PD is occurring in these 3 states and probably across the nation. After PD, MHVH hospitals had statistically better outcomes (mortality, morbidity, and duration of stay) than low-volume hospitals. Readmission rates were not affected by volume. PMID- 26897248 TI - Detection of circulating tumor cells by p75NTR expression in patients with esophageal cancer. AB - BACKGROUND: The p75 neurotrophin receptor (p75NTR) is a cancer stem cell (CSC) marker in esophageal squamous cell carcinoma (ESCC). This study aimed to assess the use of p75NTR in detecting circulating tumor cells (CTCs) in ESCC. METHODS: Peripheral blood mononuclear cell expression of epithelial cell adhesion molecule (EpCAM) and p75NTR was detected in 23 ESCC patients (13 received chemo- or chemoradiotherapy and 10 received curative surgery) and 10 healthy controls by flow cytometry. RESULTS: EpCAM+p75NTR+ cell counts (average+/-SD) were significantly higher in patients (n=23, 16.0+/-18.3) compared to controls (n=10, 0.4+/-0.9, p=0.013). The sensitivity and specificity to differentiate ESCC patients from controls were 78.3 and 100% (cut-off value 4.0), respectively. EpCAM+p75NTR+, but not EpCAM+p75NTR- cell counts, correlated with clinically diagnosed distant metastasis (n=13, p=0.006) and pathological venous invasion in resected primary tumors (n=10, p=0.016). Malignant cytology was microscopically confirmed in isolated EpCAM+p75NTR+ cells with immunocytochemical double staining. CONCLUSIONS: p75NTR is suggested to be a useful marker for clinically significant CTCs, which exhibit highly metastatic features in ESCC. PMID- 26897250 TI - Diversity of the microbiota involved in wine and organic apple cider submerged vinegar production as revealed by DHPLC analysis and next-generation sequencing. AB - Unfiltered vinegar samples collected from three oxidation cycles of the submerged industrial production of each, red wine and organic apple cider vinegars, were sampled in a Slovene vinegar producing company. The samples were systematically collected from the beginning to the end of an oxidation cycle and used for culture-independent microbial analyses carried out by denaturing high pressure liquid chromatography (DHPLC) and Illumina MiSeq sequencing of 16S rRNA gene variable regions. Both approaches showed a very homogeneous bacterial structure during wine vinegar production but more heterogeneous during organic apple cider vinegar production. In all wine vinegar samples Komagataeibacter oboediens (formerly Gluconacetobacter oboediens) was a predominating species. In apple cider vinegar the acetic acid and lactic acid bacteria were two major groups of bacteria. The acetic acid bacterial consortium was composed of Acetobacter and Komagataeibacter with the Komagataeibacter genus outcompeting the Acetobacter in all apple cider vinegar samples at the end of oxidation cycle. Among the lactic acid bacterial consortium two dominating genera were identified, Lactobacillus and Oenococcus, with Oenococcus prevailing with increasing concentration of acetic acid in vinegars. Unexpectedly, a minor genus of the acetic acid bacterial consortium in organic apple cider vinegar was Gluconobacter, suggesting a possible development of the Gluconobacter population with a tolerance against ethanol and acetic acid. Among the accompanying bacteria of the wine vinegar, the genus Rhodococcus was detected, but it decreased substantially by the end of oxidation cycles. PMID- 26897252 TI - Knowledge-light adaptation approaches in case-based reasoning for radiotherapy treatment planning. AB - OBJECTIVE: Radiotherapy treatment planning aims at delivering a sufficient radiation dose to cancerous tumour cells while sparing healthy organs in the tumour-surrounding area. It is a time-consuming trial-and-error process that requires the expertise of a group of medical experts including oncologists and medical physicists and can take from 2 to 3h to a few days. Our objective is to improve the performance of our previously built case-based reasoning (CBR) system for brain tumour radiotherapy treatment planning. In this system, a treatment plan for a new patient is retrieved from a case base containing patient cases treated in the past and their treatment plans. However, this system does not perform any adaptation, which is needed to account for any difference between the new and retrieved cases. Generally, the adaptation phase is considered to be intrinsically knowledge-intensive and domain-dependent. Therefore, an adaptation often requires a large amount of domain-specific knowledge, which can be difficult to acquire and often is not readily available. In this study, we investigate approaches to adaptation that do not require much domain knowledge, referred to as knowledge-light adaptation. METHODOLOGY: We developed two adaptation approaches: adaptation based on machine-learning tools and adaptation guided retrieval. They were used to adapt the beam number and beam angles suggested in the retrieved case. Two machine-learning tools, neural networks and naive Bayes classifier, were used in the adaptation to learn how the difference in attribute values between the retrieved and new cases affects the output of these two cases. The adaptation-guided retrieval takes into consideration not only the similarity between the new and retrieved cases, but also how to adapt the retrieved case. RESULTS: The research was carried out in collaboration with medical physicists at the Nottingham University Hospitals NHS Trust, City Hospital Campus, UK. All experiments were performed using real-world brain cancer patient cases treated with three-dimensional (3D)-conformal radiotherapy. Neural networks-based adaptation improved the success rate of the CBR system with no adaptation by 12%. However, naive Bayes classifier did not improve the current retrieval results as it did not consider the interplay among attributes. The adaptation-guided retrieval of the case for beam number improved the success rate of the CBR system by 29%. However, it did not demonstrate good performance for the beam angle adaptation. Its success rate was 29% versus 39% when no adaptation was performed. CONCLUSIONS: The obtained empirical results demonstrate that the proposed adaptation methods improve the performance of the existing CBR system in recommending the number of beams to use. However, we also conclude that to be effective, the proposed adaptation of beam angles requires a large number of relevant cases in the case base. PMID- 26897251 TI - Malignant peripheral nerve sheath tumor coexisting with congenital melanocytic nevus in an elderly man. PMID- 26897253 TI - Should the laryngeal mask airway play a role in electroconvulsive therapy? PMID- 26897255 TI - Altered functional neuronal activity in neuropsychiatric lupus: A systematic review of the fMRI investigations. AB - OBJECTIVE: Recent years have seen a rapid increase in the investigation of neuropsychiatric lupus (NPSLE) through the use of functional magnetic resonance imaging (fMRI). Measuring specific neuronal activity in regional brain structures during a cognitive task may identify possible biomarker for NPSLE. METHODS: A systematic review of fMRI studies of systemic lupus erythematosus (SLE) is carried out to address common findings that characterize NPSLE. RESULTS: A disturbance to the working memory and executive function brain regions is among the most well-replicated finding. Differences in brain activation may relate to an early primary dysfunction of these regions. Increased functional connectivity strength in the fronto-parietal cortex in the resting state is correlated with SLE disease activity in one study. Decrease functional connectivity is observed in lupus patients with long-term disease. However, there is strong evidence that points toward a lack of effective integration of distributed functional brain regions and disruptions in the subtle modulation of brain function in relation to task demands in SLE. Limitations of the literature to date include the use of small sample size and the lack of addressing the effect of confounding variables, including immunosuppressive treatment. CONCLUSION: Careful definitions of the fMRI technique used both in the design, analyses, and interpretation of high dimensional data is needed, when dealing with a limited number of SLE subjects with heterogeneous manifestations and unknown pathophysiology. PMID- 26897254 TI - Specific increase in serum core-fucosylated haptoglobin in patients with chronic pancreatitis. AB - BACKGROUND/OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) has the worst prognosis of all malignancies, and its diagnosis in early stages is the most important prognostic factor. Chronic pancreatitis (CP), a common background of PDAC occurrence, is morphologically defined as progressive pancreatic fibrosis and inflammation accompanied by pancreatic exocrine cell atrophy. We recently found that inflammation and fibrosis are independent characteristic histological changes in noncancerous lesions in PDAC patients despite the absence of a past history of clinical CP. Subclinical CP is an important background for PDAC occurrence. Therefore, there is an urgent need to develop a noninvasive and reliable biomarker for CP diagnosis. METHODS: Fifty-nine healthy volunteers (HV), 159 patients with CP, and 83 patients with PDAC were enrolled in this study. We measured serum total fucosylated haptoglobin (Fuc-Hpt) and core-Fuc-Hpt levels using lectin-antibody enzyme-linked immunosorbent assay kits that we developed. In these kits, total Fuc-Hpt and core-Fuc-Hpt were measured using Aleuria aurantia lectin and Pholiota squarrosa lectin, respectively. RESULTS: Serum Fuc Hpt levels were significantly increased in CP patients compared to HV (P < 0.0001) and were further increased in PDAC patients (P < 0.0001). Interestingly, serum core-Fuc-Hpt levels were significantly higher in CP patients compared to HV (P < 0.0001) and PDAC patients (P < 0.0001). Multivariate analyses demonstrated that total serum core-Fuc-Hpt was an independent determinant for CP diagnosis, but Fuc-Hpt was not. CONCLUSIONS: A dramatic change in oligosaccharides was observed in serum haptoglobin between CP and PDAC. Serum core-Fuc-Hpt may be a novel and useful biomarker for CP diagnosis. PMID- 26897256 TI - Growth factors and beta-tricalcium phosphate in the treatment of periodontal intraosseous defects: A systematic review and meta-analysis of randomised controlled trials. AB - OBJECTIVE: To evaluate the effectiveness at different points in time, of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) coated onto a beta-tricalcium phosphate (beta-TCP) carrier compared to beta-TCP alone, or to recombinant human growth/differentiation factor-5 (rhGDF-5) adsorbed onto a beta TCP scaffold in intraosseous periodontal defects. DESIGN: A digital search for randomised controlled trials (RCTs) was conducted on MEDLINE/PubMed. The quality of reporting and the risk of bias of the included RCTs were assessed using the CONSORT guidelines and the Cochrane risk of bias tool. The difference between the means of the outcomes at baseline and at follow-up for each group was tested using the Student's t-test for paired samples. The difference between the means of the outcome changes at follow-up between groups was analysed using the Student's t-test for two independent samples. Prior to each analysis a test of homogeneity of variances (Ansari-Bradley) was performed. RESULTS: From 11 articles assessed for eligibility, 5 RCTs were included in this review. The risk of bias was considered to be low in 2 articles, medium in 1 study and high in 2 studies. CONCLUSIONS: In the treatment of periodontal intraosseous defects the application of rhPDGF-BB/beta-TCP improved all outcomes when compared to beta-TCP at 6 months follow-up. Either rhPDGF-BB/beta-TCP or rhGDF-5/beta-TCP seemed to provide similar results in terms of probing pocket depth (PPD) reduction and clinical attachment level (CAL) gain. The application of rhGDF-5/beta-TCP resulted in a more pronounced reduction in gingival recession (GR) depth at 6 months follow-up compared to rhPDGF-BB/beta-TCP. PMID- 26897257 TI - Peri-lunate dislocation and fracture-dislocation of the wrist: Retrospective evaluation of 65 cases. AB - INTRODUCTION: Peri-lunate wrist dislocations and fracture-dislocations are related to high-energy trauma. Prognosis is often compromised because of the complexity of the lesions. The purpose of this study was to assess outcomes of acute peri-lunate injuries and correlate them with the type of lesion and management. MATERIEL AND METHODS: A monocenter retrospective study has been conducted. Sixty-five patients (65 wrists) were reviewed. According to Herzberg's classification, there were 18 isolated peri-lunate dislocations and 47 peri lunate fracture-dislocations - 27 with a scaphoid fracture and 20 with an intact scaphoid. The displacement was dorsal in 62 cases. All patients were treated surgically. RESULTS: At an average follow-up of 8 years (2-16) the average Cooney score was 66 points, quick-DASH score 21 points, and PRWE score 28 points. Pain score was 1.3 out of 10 points at rest and 4.3 out of 10 with effort. The flexion extension arc was 96 degrees with an average strength of 38kg (70+/-23% of opposite side). Radiographic analysis has shown decrease in carpal height, increase in ulnar translation, and DISI. Sign of wrist arthritis was found in 58.5% of the cases. The rate of osteonecrosis was 7.7%. Regional sympathetic painful syndrome was observed in 12%. In 26% of the cases a secondary surgery was needed. No influence has been found with the final results between fracture dislocation and isolated dislocation, and delay of treatment. Osteochondral lesions observed at surgery (P=0.035), osteonecrosis at follow-up (P=0.017), and modification of the scapho-lunate angle (P=0.029) were correlated with the occurrence of osteoarthritis. DISCUSSION: Peri-lunate dislocation and fracture dislocation represent severe wrist trauma with often numerous sequelae with follow-up: pain, stiffness, loss of strength, carpal instability and arthritis. Early diagnosis and anatomic reduction are prerequisite to a satisfactory functional result. Capsulo-ligamentous lesions must be repaired and fractures must be fixed. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV. PMID- 26897258 TI - Dyslipidemia-associated alterations in B cell subpopulation frequency and phenotype during experimental atherosclerosis. AB - Lymphocytes, the cellular effectors of adaptive immunity, are involved in the chronic inflammatory process known as atherosclerosis. Proatherogenic and atheroprotective properties have been ascribed to B cells. However, information regarding the role of B cells during atherosclerosis is scarce. Both the frequency and the phenotype of B cell subpopulations were studied by flow cytometry in wild type and apolipoprotein-E-deficient (apoE(-/-)) mice fed a high fat (HFD) or control diet. Whereas the proportion of follicular cells was decreased, transitional 1-like cells were increased in mice with advanced atherosclerotic lesions (apoE(-/-) HFD). B cells in atherosclerotic mice were more activated, indicated by their higher surface expression of CD80, CD86, CD40 and CD95 and increased serum IgG1 levels. In the aorta, a decreased frequency of B cells was observed in mice with advanced atherosclerosis. Low expression of CD19 was observed on B cells from the spleen, aorta and lymph nodes of apoE(-/-) HFD mice. This alteration correlated with serum levels of IgG1 and cholesterol. A reduction in CD19 expression was induced in splenic cells from young apoE(-/-) mice cultured with lipemic serum. These results show that mice with advanced atherosclerosis display a variety of alterations in the frequency and phenotype of B lymphocytes, most of which are associated with dyslipidemia. PMID- 26897259 TI - Association between cholesterol crystals and culprit lesion vulnerability in patients with acute coronary syndrome: An optical coherence tomography study. AB - BACKGROUND: Cholesterol Crystals (ChCs) are recognized as a hallmark of advanced atherosclerotic lesions. Previous animal and histopathology studies have revealed that Cholesterol crystallization trigger a local inflammatory response and plaque rupture. We sought to investigate the in vivo relationship between ChCs and culprit lesion vulnerability in patients with acute coronary syndrome (ACS). METHODS: 206 culprit lesions from 206 patients with ACS who underwent optical coherence tomography (OCT) imaging were divided into 2 groups based on the presence or absence of ChCs. Culprit lesions characteristics were compared between ChCs and Non-ChCs groups. RESULTS: For overall ACS patients, culprit lesions with ChCs had higher incidence of macrophages accumulation (77.8% vs. 40.0%, p < 0.001), microchannel (67.9% vs. 24.8%, p < 0.001), plaque rupture (58.0% vs. 36.0%, p = 0.001), thrombosis (66.7% vs. 49.6%, p = 0.016) and spotty calcification (35.8% vs. 10.4%, p < 0.001). In addition, the mean lipid arc (274.2 +/- 57.6 degrees vs. 228.1 +/- 66.3 degrees , p < 0.001) was larger and the lipid index (3826.1 +/- 2111.4 vs. 2855.0 +/- 1753.0, p = 0.001) was greater. The frequency of ChCs was significantly higher in patients with STEMI, as compared with NSTEACS (50.8% vs. 34.7%, p = 0.032). Larger lipid arc, higher incidence of macrophages accumulation and that of microchannel were observed in culprit lesions with ChCs in both STEMI (p = 0.028, p < 0.001, and p = 0.002 respectively) and NSTEACS (p < 0.001, p < 0.001, and p < 0.001 respectively) subgroups. CONCLUSION: ChCs were frequently associated with characteristics of vulnerable plaques in ACS culprit lesions as well as in STEMI and NSTEACS subgroups. ChCs and vulnerable plaque features were more often observed in culprit lesions of STEMI patients compared to NSTEACS patients. PMID- 26897260 TI - Topologic distributions of vasa vasorum and lymphatic vasa vasorum in the aortic adventitia--Implications for the prevalence of aortic diseases. AB - BACKGROUND AND AIMS: Vasa vasorum (VV) and lymphatic vasa vasorum (LVV) form their own networks in the adventitia. VV supply the aorta with nutrition and oxygen; however, the distribution and role of LVV remains to be determined. The purpose of this study was to investigate differences in the distribution of VV and LVV along the aorta. METHODS: Aortic samples were obtained from 22 autopsy cases without medical history of aortic diseases. Aortic segments were classified as arch (Ar), descending thoracic (De), suprarenal abdominal (S-Ab), and infrarenal abdominal (I-Ab). Adventitial VV and LVV were identified immunohistochemically. RESULTS: VV were most dense in the arch aorta, becoming less dense along the aorta in more distal segments, with the lowest density occurring in the infrarenal abdominal aorta. There was a significant correlation between the numbers of VV and medial thickness in the total aortic segments (r = 0.518, p < 0.01). In contrast, there was no significant correlation between the number of LVV and medial thickness in any aortic segments. However, there was a significant correlation between the number of LVV and intimal thickness in I-Ab (r = 0.425, p < 0.05). CONCLUSIONS: The distributions of adventitial VV and LVV were characteristic along the aortic segments. Differences in the distributions may imply the prevalence of aortic diseases such as dissection, abdominal aortic aneurysm, and atherosclerotic occlusive disease in each aortic segment. PMID- 26897261 TI - Complimentary lower-level and higher-order systems underpin imitation learning. AB - We examined whether the temporal representation developed during motor training with reduced-frequency knowledge of results (KR; feedback available on every other trial) was transferred to an imitation learning task. To this end, four groups first practised a three-segment motor sequence task with different KR protocols. Two experimental groups received reduced-frequency KR, one group received high-frequency KR (feedback available on every trial), and one received no-KR. Compared to the no-KR group, the groups that received KR learned the temporal goal of the movement sequence, as evidenced by increased accuracy and consistency across training. Next, all groups learned a single-segment movement that had the same temporal goal as the motor sequence task but required the imitation of biological and nonbiological motion kinematics. Kinematic data showed that whilst all groups imitated biological motion kinematics, the two experimental reduced-frequency KR groups were on average ~ 800 ms more accurate at imitating movement time than the high-frequency KR and no-KR groups. The interplay between learning biological motion kinematics and the transfer of temporal representation indicates imitation involves distinct, but complementary lower-level sensorimotor and higher-level cognitive processing systems. PMID- 26897262 TI - PtW/MoS2 hybrid nanocomposite for electrochemical sensing of H2O2 released from living cells. AB - Hydrogen peroxide (H2O2) as an important reactive oxygen species (ROS) is reactive and potentially harmful to cells, causing oxidation of lipids, proteins and DNA. Herein, we report a PtW/MoS2 hybrid nanocomposite with ultrasensitive and highly specific response for the detection of H2O2 released from breast cancer 4T1 cells. Upon exposure to 5 nM of H2O2, the electrochemical response is still visible. This PtW/MoS2 hybrid nanocomposite could be facilely synthesized through in-situ growth of PtW nanocrystals on the surface of MoS2 nanosheets. The incorporation of PtW nanocrystals and MoS2 nanosheets in conjunction with each other to form hybrid nanocomposite improves the selective interaction of H2O2 with sensing material surface, and further increases the sensitivity and selectivity of sensor. PMID- 26897264 TI - The development of the perception of audiovisual simultaneity. AB - We measured the typical developmental trajectory of the window of audiovisual simultaneity by testing four age groups of children (5, 7, 9, and 11 years) and adults. We presented a visual flash and an auditory noise burst at various stimulus onset asynchronies (SOAs) and asked participants to report whether the two stimuli were presented at the same time. Compared with adults, children aged 5 and 7 years made more simultaneous responses when the SOAs were beyond +/- 200 ms but made fewer simultaneous responses at the 0 ms SOA. The point of subjective simultaneity was located at the visual-leading side, as in adults, by 5 years of age, the youngest age tested. However, the window of audiovisual simultaneity became narrower and response errors decreased with age, reaching adult levels by 9 years of age. Experiment 2 ruled out the possibility that the adult-like performance of 9-year-old children was caused by the testing of a wide range of SOAs. Together, the results demonstrate that the adult-like precision of perceiving audiovisual simultaneity is developed by 9 years of age, the youngest age that has been reported to date. PMID- 26897265 TI - Charles M. Mansbach, MD, 1937-2015. PMID- 26897263 TI - Label-free electrochemical impedance biosensor to detect human interleukin-8 in serum with sub-pg/ml sensitivity. AB - Biosensors with high sensitivity and short time-to-result that are capable of detecting biomarkers in body fluids such as serum are an important prerequisite for early diagnostics in modern healthcare provision. Here, we report the development of an electrochemical impedance-based sensor for the detection in serum of human interleukin-8 (IL-8), a pro-angiogenic chemokine implicated in a wide range of inflammatory diseases. The sensor employs a small and robust synthetic non-antibody capture protein based on a cystatin scaffold that displays high affinity for human IL-8 with a KD of 35 +/- 10 nM and excellent ligand specificity. The change in the phase of the electrochemical impedance from the serum baseline, ?theta(f), measured at 0.1 Hz, was used as the measure for quantifying IL-8 concentration in the fluid. Optimal sensor signal was observed after 15 min incubation, and the sensor exhibited a linear response versus logarithm of IL-8 concentration from 900 fg/ml to 900 ng/ml. A detection limit of around 90 fg/ml, which is significantly lower than the basal clinical levels of 5 10 pg/ml, was observed. Our results are significant for the development of point of-care and early diagnostics where high sensitivity and short time-to-results are essential. PMID- 26897266 TI - Does the Presence of Endometrial Polyp Predict Colorectal Polyp? AB - INTRODUCTION: Endometrial polyps (EPs) and colorectal polyps (CPs) are common disorders and the incidence of both increase rapidly with aging. CPs are focal lesions and incidence increases with age. AIM: In this study, we aimed to analyze retrospectively the relationship between the EPs and CPs sharing similar clinical and genetic factors in their etiopathogenesis. MATERIALS AND METHODS: This study was retrospectively performed between 2010 and 2013 and it included patients diagnosed to have eEPs. The study group and the control group consisted of patients who were diagnosed with or without EPs and who underwent colonoscopy at the same period. RESULTS: The study group was formed by 57 patients with diagnosis of EP who underwent colonoscopy during the same period. The control group consisted of 71 patients without EP examined with colonoscopy. Among 128 patients assessed in this study, 24 were diagnosed with CPs, all of which were adenomatous polyps smaller than 1cm. No hyperplastic or inflammatory polyps were diagnosed. While 18 of 57 patients with EPs had CPs, 6 of 71 control subjects had CPs. Hence, the risk of having CP was 5 times greater in patients with EP compared to those without (P < 0.05). CONCLUSION: The present study demonstrated that the prevalence of CPs increased significantly in postmenopausal patients with EPs. Recommending colonoscopy to these patients irrespective of age may be beneficial for detecting more CPs and preventing colorectal cancer. PMID- 26897267 TI - Newer QT Correction Formulae to Correct QT for Heart Rate Changes During Exercise. AB - BACKGROUND: The QT interval is a marker for drug-induced cardiac toxicity, electrolyte abnormalities and genetic mutations with a high risk of sudden death. AIM: The objective was to determine the optimal QT-heart rate correction when heart rate is increased. MATERIALS AND METHODS: A total of 40 persons had QT interval measured before at the end of each stage of a Bruce protocol. Currently used heart rate correction formulae (QTc) were compared to recently proposed QTc formulae derived from large population studies. RESULTS: Comparing the data at each stage of exercise found that QTc using the Bazett formula (QTcBZT) increased with exercise while the QTc proposed by Fridericia (QTcFRD) and by Framingham (QTcFRM) decreased with exercise. In contrast QTc proposed by Dmitrienko (QTcDMT) and Rautaharju (QTcRTHa) were relatively constant despite the increase in heart rate during exercise, whereas QTc proposed by Hodges (QTcHDG) was more variable. With exercise, the differences between QTcBZT or QTcFRD and the other correction formulae became greater and highly significant. Next, the slope of QTc or RR regression was calculated for each individual during the exercise test. The rank order of the slopes (from the smallest to largest absolute value) was QTcRTHa, QTcDMT, QTcBZT, QTcHDG, QTcFRD and QTcFRM. Furthermore the slope of the QT/heart rate relationship was significantly (P < 0.0001) different between the older formulae proposed by Bazett or Fridericia compared to the newer formulae QTcDMT or QTcRTHa. CONCLUSION: The 2 newer QT-heart rate correction formula should be used when evaluating QT interval at faster heart rates especially those associated with exercise. PMID- 26897268 TI - Nucleated Red Blood Cell Count in Maternal Peripheral Blood and Hypertensive Disorders in Pregnant Women. AB - OBJECTIVE: We investigated the correlations of nucleated red blood cell (NRBC) counts with hypertensive disorders in pregnancy (HDP) and fetal umbilical blood flow velocity. MATERIALS AND METHODS: We recruited 282 patients with HDP as experimental group including 107 with mild pre-eclampsia (A1 group), 100 with severe pre-eclampsia (A2 group) and 75 with eclampsia (A3 group), and 215 normal pregnant women as control group. Maternal peripheral venous blood was collected and isolated cells were stained with Wright-Giemsa. We estimated NRBC counts according to laboratory routine and Doppler ultrasound examinations were employed to measure the systolic/diastolic (S/D) ratios of fetal ductus venosus, umbilical artery and middle cerebral artery. RESULTS: The NRBC counts in A1, A2 and A3 groups were higher than control group (all P < 0.01). The S/D ratios in control, A1, A2 and A3 groups increased orderly (P < 0.05). Receiver operating characteristic curve analysis demonstrated that the sensitivity and specificity of NRBC count and S/D ratios in diagnosing HDP were 96.50% and 96.28%; 93.60% and 98.14%; 94.30% and 94.88% 99.30% and 100%, respectively. Pearson and Spearman correlation analysis revealed that the NRBC and S/D ratios were correlated with gestational age at birth, amniotic fluid volume, premature birth, mechanical ventilation, neonatal intensive care unit admission, neonatal asphyxia, birth weight, fetal distress, APGAR score, pH value, arterial oxygenation tension, bicarbonate and base excess (all P < 0.05). The NRBC count was positively associated with the S/D ratios (all P < 0.05). CONCLUSIONS: Our results provide evidence that NRBC count in patients with HDP increased significantly, showing positive correlations with umbilical S/D ratios. PMID- 26897269 TI - Circulating Progenitor Cells is Linked to Cognitive Decline in Healthy Adults. AB - OBJECTIVE: Cognitive and cardiovascular disorders share many risk factors. Higher bone-marrow derived progenitor cells (PC) in blood are associated with lower rates of cardiovascular events but the association of PC with cognitive function is unclear. The objective of this study was to assess the association between PC and cognition in a sample of healthy adults enrolled in a cohort study. MATERIALS AND METHODS: A random sample of employees at Emory University and Georgia Institute of Technology were followed for 4 years and underwent yearly vascular and cognitive assessment (N = 430, mean age = 49.2 years, 70% women, and 27% African-American). Cognition was assessed using computerized versions of 15 cognitive tests and principal component analysis was used for deriving cognitive scores: executive function, memory and working memory. PC were defined as mononuclear cells with specific surface markers (7 phenotypes). Decreased cognition in a domain was defined as performing below the lowest quartile for the corresponding domain at baseline. Generalized estimating equations were used to investigate associations between PC and cognition. RESULTS: Higher PC levels at baseline were associated with lower risk of cognitive decline in the executive and working memory domains during the follow-up period (P < 0.002 for all PC phenotypes). Further, the degree of decline in PC over the follow-up period was correlated with a corresponding decline in performances in all 3 cognitive domains over the same period (All P < 0.002). CONCLUSION: Lower PC and greater yearly declines in PC are associated with greater cognitive decline. These findings suggest the role for PC in neurocognitive aging. PMID- 26897270 TI - Neutrophilic Loculated Tuberculous Pleural Effusion: Incidence, Characteristics and Differentiation From Complicated Parapneumonic Effusion. AB - OBJECTIVES: Tuberculous pleural effusion (TPE) is generally characterized by lymphocytic exudative effusion, either free-flowing or loculated. However, patients can also have neutrophilic loculated TPE, although little data are available concerning the incidence and characteristics of this form of TPE. It is important to differentiate between neutrophilic loculated TPE and complicated parapneumonic effusion (PPE), which also shows neutrophilic loculated effusion but needs a different management approach. The present study evaluated the incidence and characteristics of neutrophilic loculated TPE and differentiated it from complicated PPE. MATERIALS AND METHODS: Between 2009 and 2014, a cohort of patients with TPE was retrospectively reviewed in a South Korean referral hospital. Clinical, laboratory, computed tomography and pleural fluid findings of patients with neutrophilic loculated TPE were compared to those of patients with neutrophilic free-flowing TPE and complicated PPE, respectively. RESULTS: Neutrophilic TPE was observed in 33 (10%) out of 344 patients with TPE. Of these, 10 (30%) patients exhibited loculation of the pleural fluid. These patients showed distinct pleural fluid characteristics. The classical pleural fluid biomarker levels were more intense than those observed in 23 patients with neutrophilic free-flowing TPE, but similar to those of 54 patients with complicated PPE. A high mycobacterial burden was observed in the pleural fluid, and favorable outcomes were achieved with antituberculosis drug administration alone. Nodular parenchymal lesions and pleural fluid adenosine deaminase levels were independent discriminators of neutrophilic loculated TPE and PPE. CONCLUSIONS: These results may be helpful to understand and manage patients with neutrophilic loculated TPE and differentiate them from patients with complicated PPE. PMID- 26897271 TI - Nocturnal Hypoxemia Causes Hyperglycemia in Patients With Obstructive Sleep Apnea and Type 2 Diabetes Mellitus. AB - BACKGROUND: Our purpose was to investigate the relationship between oxygen saturation (SpO2) and dynamic interstitial glucose level (IGL) in patients with obstructive sleep apnea (OSA) along with type 2 diabetes mellitus (T2DM), and to investigate the potential mechanisms thereof. MATERIALS AND METHODS: A total of 130 patients with OSA and T2DM underwent polysomnography and oral glucose tolerance tests at the Sleep Medicine Center. Using the lowest (L) SpO2% tested, patients were divided into mild, moderate and severe LSpO2 groups. Polysomnography and continuous glucose monitoring systems were used to analyze the altered pattern of SpO2 and dynamic IGL in the 3 groups. RESULTS: LSpO2 during sleep in patients with OSA and T2DM stimulated an increase in IGL. The moderate and severe levels were represented by IGL45 and IGL30, respectively. The average nocturnal and peak IGL after LSpO2 in the severe group were significantly higher than in the mild and moderate groups. Stepwise multiple regression analysis showed that the body mass index (beta = 0.301, P < 0.001), homeostatic model assessment of insulin resistance (beta = 0.260, P < 0.001), apnea-hypopnea index (beta = 0.309, P < 0.001), average SpO2 (beta = -0.423, P = 0.008), LSpO2 (beta = -0.369, P < 0.001) and microarousal index (beta = 0.335, P = 0.044) were probably related to nocturnal IGL in patients with OSA along with T2DM. CONCLUSIONS: Severe and moderate OSA with T2DM is marked by a delayed IGL peak following LSpO2. Nocturnal hypoxemia causes hyperglycemia in patients with OSA along with T2DM. PMID- 26897272 TI - The Beneficial Effect of Beta-Blockers in Patients With Cirrhosis, Portal Hypertension and Ascites. AB - BACKGROUND: Patients with cirrhosis and portal hypertensive complications have reduced survival. As such, it has been suggested that nonselective beta-blocker therapy in patients with advanced ascites is harmful. The aim of this study was, therefore, to determine the risk of mortality in patients with cirrhosis and ascites taking nonselective beta-blocker therapy for the prevention of variceal hemorrhage. MATERIALS AND METHODS: This study was a retrospective analysis of 2,419 patients with cirrhosis and portal hypertension admitted to Parkland Memorial Hospital (a university-affiliated county teaching hospital) from 2003 2010. Patients were subdivided into those with varices only, ascites only and those with both varices and ascites. The primary outcome measure for this study was all-cause in-hospital mortality. RESULTS: Overall, 68 of 1,039 (6.5%) patients taking beta-blockers died during their hospitalization, while 223 of 1,380 (16.2%) patients not taking beta-blockers died (P < 0.001). Beta-blocker use was also assessed in specific cohorts; mortality was 21.1% in patients with severe ascites with varices who were not taking beta-blockers compared with 8.9% in patients who were taking beta-blockers (P = 0.05). Overall, fewer patients taking beta-blockers died compared with those not taking beta-blockers in patients with varices only (6.4% versus 12.1%) and those with ascites with or without varices (6.6% versus 18.1%) (P < 0.001). CONCLUSIONS: Mortality was lower in patients with cirrhosis and portal hypertension taking nonselective beta blockers than in those not taking beta-blockers. The use of nonselective beta blockers provided a significant survival benefit in patients with all grades of ascites, including those with severe ascites. PMID- 26897273 TI - Central Nervous System Histoplasmosis in Acquired Immunodeficiency Syndrome. AB - BACKGROUND: Involvement of the central nervous system (CNS) by Histoplasma capsulatum in AIDS is uncommon and not easily recognized. MATERIALS AND METHODS: CNS histoplasmosis cases from our institution were identified by a retrospective chart review from 2004-2014. A thorough literature search was performed for additional cases and their characteristics were compared. Clinical findings, treatment and outcomes are discussed. RESULTS: A total of 5 cases from our institution were identified. They had a clinical presentation that included classic signs of meningitis, often with evidence of disseminated involvement, and was typically severe with important neurological impairment. These cases were treated with antifungal agents, including a lipid amphotericin B formulation and azole drugs, but eventually 3 experienced nonresolution of their disease likely because of lack of adherence to therapy and died from their infection. The clinical presentation, treatment and outcome of these cases did not significantly differ from cases found in the review of the literature. CONCLUSIONS: Clinicians practicing in endemic areas should be aware of this rare but serious form of histoplasmosis. The recognition of 5 cases of CNS histoplasmosis in AIDS patients from a single institution suggests that histoplasmosis should be included in the differential diagnosis of the CNS complications of AIDS. PMID- 26897274 TI - Unequal Arterial Stiffness With Overall and Cardiovascular Mortality in Patients Receiving Hemodialysis. AB - BACKGROUND: Pulse wave velocity is a marker of arterial stiffness. Unequal arterial stiffness has been associated with increased risk of cardiovascular events. This study calculated bilateral brachial-ankle pulse wave velocity (baPWV) differences and investigated the associations of unequal bilateral baPWV with overall and cardiovascular mortality in patients receiving hemodialysis (HD). MATERIALS AND METHODS: A total of 205 patients receiving HD were enrolled in this study. The mean follow-up period was 4.4 +/- 1.5 years. The baPWV was measured using an ankle-brachial index-form device, and bilateral baPWV difference was calculated and defined as DeltabaPWV. RESULTS: The median value of DeltabaPWV was 88cm/second. ankle-brachial index < 0.95 and high baPWV were independently associated with a DeltabaPWV >= 88cm/s. Furthermore, patients with a DeltabaPWV >= 88cm/s demonstrated poorer overall (log-rank P = 0.035) and cardiovascular (log-rank P = 0.036) survival than did those with a DeltabaPWV < 88cm/s. After multivariate analysis, this difference was independently associated with overall (hazard ratio = 1.006; 95% CI: 1.001-1.011; P = 0.024) and cardiovascular (hazard ratio = 1.006; 95% CI: 1.000-1.013; P = 0.049) mortality. CONCLUSIONS: DeltabaPWV was associated with an increased risk of cardiovascular and overall mortality in patients receiving HD. Earlier evaluation of DeltabaPWV may facilitate the identification of patients receiving HD who have an increased risk of cardiovascular and overall mortality. PMID- 26897275 TI - Cardiomyopathy Associated With Targeted Therapy for Breast Cancer. AB - BACKGROUND: Chemotherapeutic agents directed against human epidermal growth factor receptor 2 (HER-2) have significantly improved the prognosis of patients who are positive for this receptor. However, cardiomyopathy remains as a common adverse effect of using these agents. MATERIALS AND METHODS: Literature search was conducted via PubMed using the keywords of "Trastuzumab Cardiomyopathy," "Lapatinib Cardiomyopathy" and "Pertuzumab Cardiomyopathy," which provided 104 results. These articles were then screened for relevance to the targeted subject based on their title and abstracts. Case reports and articles that were not discussing any aspect of cardiomyopathy secondary to targeted therapy for breast cancer and articles not in English were eliminated. After elimination, a bibliography search among selected articles was done and a total of 46 articles were identified. The collected articles were then meticulously analyzed and summarized. RESULTS: The use of human epidermal growth factor receptor 2 (HER-2) receptor targeted chemotherapy in breast cancer is limited because of a higher incidence (19-22%) of cardiomyopathy. The incidence of cardiomyopathy is not dose dependent and in most cases it is reversible after discontinuation of the drug and treatment with heart failure medications. Severe adverse outcomes including death or permanent disability are rare. CONCLUSION: HER-2 targeted chemotherapy for breast cancer has a higher incidence of associated reversible cardiomyopathy. Patients should be monitored by serial echocardiography starting at the beginning of the treatment and followed by every 3 months until the completion of chemotherapy. Co-ordination between oncologists and cardiologists is needed to develop evidence-based protocols to prevent, identify, monitor and treat trastuzumab-induced cardiomyopathy. PMID- 26897276 TI - Acute Anterior ST-Segment Elevation Myocardial Infarction Caused by Occlusion of Right Coronary Artery. PMID- 26897277 TI - The Effect of Short-Term Hyperglycemia on the Innate Immune System. AB - BACKGROUND: Diabetes mellitus increases the susceptibility to infection by altering both the innate and the adaptive immune systems. Hyperglycemia has been associated with adverse outcomes in hospitalized patients, especially critically ill patients; these poor outcomes are explained in part by hospital-associated infections. MATERIALS AND METHODS: PubMed, EMBASE and Google Scholar were searched to identify studies published between 1970 and 2014 reporting short-term effects of hyperglycemia on the innate immune system. MeSH database search terms included hyperglycemia, immune system, inflammation, inflammation mediators, neutrophils, endothelial dysfunction, complement system proteins and diabetes. Pertinent articles reported studies in healthy volunteers and diabetic patients, using in vitro laboratory experiments, and with animal models. RESULTS: Hyperglycemia activates protein kinase C, and this inhibits neutrophil migration, phagocytosis, superoxide production and microbial killing. High glucose concentrations decrease the formation of neutrophil extracellular traps. Hyperglycemia can also induce Toll-like receptor expression and inhibit neutrophil function and apoptosis. High glucose concentrations decrease vascular dilation and increase permeability during the initial inflammatory responses, possibly through protein kinase C activation. Hyperglycemia can cause direct glycosylation of proteins and alter the tertiary structure of complement; these changes inhibit immunoglobulin-mediated opsonization of bacteria and complement fixation to bacteria and decreases phagocytosis. Hyperglycemia also stimulates the production and release of cytokines. Several trials have demonstrated that better glycemic control reduces nosocomial infections in critically ill patients and surgical site infections. CONCLUSIONS: In summary, acute hyperglycemia can significantly alter innate immune responses to infection, and this potentially explains some of the poor outcomes in hospitalized patients who develop hyperglycemia. PMID- 26897278 TI - Autoimmune Hyperthyroidism, Vitiligo, Halo Nevus and Lupus. PMID- 26897279 TI - Efavirenz-Associated Urinary Matrix Stone-A Rare Presentation. PMID- 26897280 TI - Reversible Godot Syndrome in an Elderly Patient With Frontal Lobe Meningioma. PMID- 26897281 TI - Calciphylaxis: Controversies in Pathogenesis, Diagnosis and Treatment. AB - Calcific uremic arteriolopathy, otherwise known as calciphylaxis, is a rare disease characterized by skin ulceration and tissue necrosis, likely the result of vascular calcification with accompanying intimal hypertrophy and small vessel thrombosis. Although most often associated with end-stage renal disease, it has also been seen in a number of other disorders (collectively referred to as nonuremic calciphylaxis). The purpose of this review is to summarize and analyze the currently available literature regarding the pathophysiology, risk factors, clinical presentation, diagnostic features and treatment modalities for this exceptionally uncommon illness. A series of recommended treatments is proposed for optimal treatment of calciphylaxis lesions. PMID- 26897282 TI - Central Venous Catheter-Associated Right Atrial Thrombus. PMID- 26897283 TI - Oral and inhaled corticosteroid use and risk of recurrent pulmonary embolism. AB - INTRODUCTION: Chronic inflammatory diseases predispose for development of a first pulmonary embolism (PE). Previous studies showed that corticosteroids, which are the mainstay of treatment for inflammatory diseases, enhance the risk of a first venous thromboembolism. Yet, it is unknown whether corticosteroids also predispose for recurrent events. Therefore, we investigated the association between oral and/or inhaled corticosteroid use and the risk of recurrent PE. METHODS: We performed a nested case-control study using the PHARMO Database. Adult patients who had suffered from a first PE for which vitamin K antagonists were prescribed, were eligible. Of these, 384 patients with recurrent PE were matched to 1030 patients without recurrent PE. RESULTS: We showed that oral or inhaled corticosteroids was ever used by 22.7% and 20.6% of patients with recurrent PE, and 23.5% and 21.5% of the patients without recurrent PE. There was an overall association between oral corticosteroid use and the risk of recurrent PE (p=0.02). Current use of oral corticosteroids increased the risk of recurrent PE (OR 3.74; 95% CI 2.04-6.87), whereas past use reduced the risk (OR 0.46; 95% CI 0.28-0.74). A similar pattern was observed for inhaled corticosteroids, although less strong (p=0.10). CONCLUSIONS: Current use of oral corticosteroids is associated with increased risk of recurrent PE. Whether this increased risk is caused by oral corticosteroids themselves, or by the underlying disease, or both, needs further investigation. Nevertheless, given the frequent use of corticosteroids in clinical practice, clinicians should be aware of this risk. PMID- 26897285 TI - Calling a "cat a cat": has the time come to return to "valvular disease" from "structural heart"? PMID- 26897284 TI - Probucol inhibits MMP-9 expression through regulating miR-497 in HUVECs and apoE knockout mice. AB - OBJECTIVE: This study investigated the molecular mechanisms underlying the inhibition of MMP-9 expression by probucol, which is widely used for atherosclerotic prevention, in cultured human umbilical vein endothelial cells (HUVECs) and apoE knockout mice. MATERIALS AND METHODS: We used three target scan algorithms and observed that microRNA (miR)-497 targeted MEK1, a member of the MAPK/ERK signaling involved in regulating MMP-9 expression. HUVECs were treated with TNFalpha, and apoE knockout mice were fed a high-fat/high-cholesterol diet with or without probucol pretreatment. We focused on the association between miR 497 and MAPK/ERK signaling and MMP-9 expression. RESULTS: First, miR-497 expression was significantly higher in the probucol-treated HUVECs and apoE knockout mice compared with non-probucol-treated HUVECs and apoE knockout mice (both p<0.05). Second, MAPK/ERK signaling and MMP-9 levels were downregulated in probucol-treated HUVECs that were treated with TNFalpha (p<0.01), while MAPK/ERK signaling and MMP-9 levels were upregulated after suppression of miR-497 (p<0.01). Third, probucol increased miR-497 expression levels in the aortas of apoE knockout mice (p<0.05) while decreasing the levels of serum lipids and plaque areas (p<0.05), which decreased the MAPK/ERK signaling and MMP-9 levels (p<0.05). CONCLUSIONS: Probucol inhibits MMP-9 expression through regulating miR 497 in HUVECs and apoE knockout mice. PMID- 26897286 TI - Accurate procedural assessment of AR - critical for successful TAVI. PMID- 26897287 TI - Mitral valve-in-ring: the good, the bad, and the ugly. PMID- 26897288 TI - Percutaneous paravalvular leak closure? Perhaps a glimmer of hope after a long course of marginal success. PMID- 26897289 TI - Outcome with invasive versus medical treatment of stable coronary artery disease: influence of perfusion defect size, ischaemia, and ejection fraction. AB - AIMS: Our aim was to address the combined influence of myocardial perfusion defects and left ventricular ejection fraction (LVEF) on outcome with coronary revascularisation in stable CAD patients. METHODS AND RESULTS: Of 527 patients with ischaemia by myocardial perfusion scintigraphy, 343 had medical therapy (Med) and 184 revascularisation (Revasc). During 5.3 years of follow-up, there was no intergroup difference in rates of death/myocardial infarction. Propensity score adjustment demonstrated a benefit of Revasc over Med with large defects (>14% of the myocardium), marked ischaemia (>10% of the myocardium), or LVEF <50%. However, defect size, ischaemia, and LVEF were correlated. In multivariate models, the Med versus Revasc hazard ratio (HR) was 4.06 times larger for LVEF <50% than for LVEF >=50% (p=0.04) and 3.01 times larger for marked compared to mild/moderate ischaemia (p=0.11), whereas the effect of large compared to small/moderate defects vanished when adjusted for LVEF and ischaemia (HR=1.01, p=0.99). Considering the outcome difference as a function of both LVEF and ischaemia, we found no advantage or even a disadvantage of revascularisation in patients with mild/moderate ischaemia and preserved LVEF. CONCLUSIONS: A benefit of revascularisation was found only in case of marked ischaemia or LVEF <50%. For treatment triage, both perfusion parameters and LVEF should be considered. PMID- 26897290 TI - Acute LAD occlusion by calcified plaque embolisation from the ascending aorta after contralateral LCA angiography. PMID- 26897291 TI - Feasibility and safety of balloon-expandable transcatheter aortic valve implantation with moderate or without predilatation. AB - AIMS: Aortic valve preparation by performing balloon aortic valvuloplasty (BAV) has always been considered mandatory during transcatheter aortic valve implantation (TAVI) procedures. We aimed to investigate the feasibility and safety of performing balloon-expandable TAVI with moderate or with no predilatation (PD). METHODS AND RESULTS: Overall, 121 patients underwent TAVI with no PD and 392 with moderate PD. TAVI endpoints and adverse events were considered according to the Valve Academic Research Consortium (VARC)-2 definitions. Device success for the entire cohort was 95.1%. Post-dilatation was performed in nine patients in the no PD group (7.4%) and in 40 patients in the moderate PD group (10.2%) (p=0.06). Total fluoroscopy time and the amount of contrast used were lower in the no PD group. All-cause mortality up to 30 days was 3.3% in the no PD group vs. 3.6% in the moderate PD group (p=0.89). VARC-2 defined complication rates at 30 days including cerebrovascular accident (CVA)/transient ischaemic attack (TIA) were similar between groups. Overall, there was no significant difference in survival rates between the two groups (HR 1.33, 95% CI: 0.75-2.35; p=0.34). CONCLUSIONS: Balloon-expandable TAVI with moderate or without balloon PD is feasible and safe. The omission of PD in appropriate cases was associated with reduced fluoroscopy time without affecting procedural success. PMID- 26897292 TI - Early experience of percutaneous paravalvular leak closure using a novel Occlutech occluder. AB - AIMS: Paravalvular regurgitation is an important complication of mitral valve replacement. Although surgical repair is mostly recommended, it is associated with significant morbidity. On the other hand, percutaneous closure is a less invasive alternative approach. Percutaneous approaches to treatment of paravalvular prosthetic regurgitation have emerged recently. One of them is the Occlutech Paravalvular Leak Device. The aim of this study was to evaluate early and midterm outcomes of percutaneous paravalvular leak closure utilising a novel occluder. METHODS AND RESULTS: Twenty-one consecutive symptomatic patients who had moderate or severe paravalvular prosthetic regurgitation on transoesophageal echocardiography were included in the study. All the patients were clinically evaluated and found inoperable for surgery. They underwent transapical repair with the Occlutech Paravalvular Leak Device. The patients were followed for 17+/ 5 months. Attempts were made to rectify 41 defects in 21 patients with 100% success. Mean procedure time was 76+/-40 min and fluoro-scopy time was 44+/-37 min. Early post-procedural outcome was uneventful in all cases, with >=1 grade reduction in regurgitation in all of the patients. There was no mortality during hospital stay. There was one case of haemothorax in one patient and one case of pneumothorax in another. Post-implantation 90-day follow-up data were obtained for 19 patients, and 12-month data were obtained for 12 patients. No deaths due to any cause, stroke or surgery for prosthetic impingement, worsening or relapse of paravalvular leak during follow-up were recorded. One patient underwent reintervention and was treated successfully with the same occluder 11 months after the index procedure. CONCLUSIONS: The novel Occlutech Paravalvular Leak Device, which was designed specifically for mitral and aortic paravalvular regurgitation, is an additional, useful tool in the device armamentarium for the treatment of PVL. PMID- 26897293 TI - How should I treat refractory cardiogenic shock in a patient with chronic biventricular heart failure and mitral regurgitation with difficult valve characteristics? PMID- 26897294 TI - Low compliance to pharmacological treatment is linked to cognitive impairment in euthymic phase of bipolar disorder. AB - BACKGROUND: Cognitive impairment and low compliance to pharmacological treatment are frequent complications in bipolar disorder. Moreover, low compliance in patients with bipolar disorder is one of the main reasons for relapse. This in turn, is associated with an increase in neurocognitive symptoms. The current study aimed to determine whether attention, memory, and executive function are related to the level of compliance to pharmacological treatment in individuals with bipolar disorder in euthymic phase. METHOD: We examined 34 patients with bipolar disorder (12 with low compliance to the treatment and 22 with high compliance to the treatment) according to the DSM-IV criteria, in the range of 18 55 years. All patients were assessed through a neuropsychological battery in one single session. Analysis of covariance (ANCOVA) was used to compare neuropsychological test scores between low and high compliance patients. Clinical and sociodemographic characteristics were included as covariates in the study. RESULTS: Patients with low level of compliance performed significantly worse than high treatment compliance on verbal memory immediate free recall (F (1)=12.14, p=.002), verbal memory immediate cued recall (F (1)=10.45, p=.003), verbal memory delayed free recall (F (1)=5.52, p=.027), and verbal memory delayed cued recall (F (1)=6.11, p=.021). Covariates such as number of manic episodes, history of psychosis and years of education were found significant for executive functions and processing speed. CONCLUSION: We found that low compliance to pharmacological treatment is consistently linked to immediate and delayed verbal memory. In addition, executive function and processing speed were associated with clinical and demographic characteristics. Limitations of this study include the small sample size, a cross-sectional design that cannot address causality, and inability to account for pharmacologic effects. PMID- 26897295 TI - Carbopol(r)-crospovidone interpolymer complex for pH-dependent desloratadine release. AB - Hydrogen-bonded interpolymer complexes are prepared using special polymers interactions between relatively weak hydrogen bonds and other components when they are numerous with consecutive configurations. Drug molecules possessing hydrogen donor or acceptor groups or both intercalate into the complex and show different release patterns. While numerous studies have investigated polymer component behaviours in different media and the resulting drug release profiles, few have focused on the specific drug molecule state. Desloratadine was incorporated into a Carbopol((r))-polyvinylpyrrolidone (PVP) complex using a novel method and the dissolution and release profiles as well as the mediating interactions were investigated at different pH values. Our results indicate that the drug showed an immediate release pattern at an acidic pH, and therefore, the polymer complex likely had no dissolution retarding effect on the developed system. Furthermore, the protonated state of the drug enhanced its detachment from the polymer and subsequent dissolution in the medium. Contrastingly, higher pH values around the pKa of pyridine nitrogen strongly suppressed the dissolution in an exponential-like manner. This suggests that in addition to dissociating both linked polymers or dissolving one polymer group, active groups that facilitate hydrogen bonding can also play an important role in the release mechanism. PMID- 26897296 TI - Organohalogenated contaminants in type 2 diabetic serum from Jeddah, Saudi Arabia. AB - Most of the organohalogenated contaminants (OHCs) have high environmental stability and are lipophilic in nature, thus bioaccumulate through the various routes e.g., inhalation, dermal contact and food intake. Human exposure to these OHCs can induce adverse health effects. Studies on the occurrence of OHCs in human samples from Saudi Arabia are scarce. Therefore, this study aimed at providing preliminary insight on the occurrence of polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs) and polybrominated biphenyl ethers (PBDEs) in diabetic and non-diabetic donors from KSA. Serum samples were collected from type 2 diabetic patients (n = 40) and control donors (n = 20) to study the impact of OHCs on their health. For the first time we studied the difference of ?OHCs in type 2 diabetic and control participants. The order of obtained results was ?OCPs (35-650 ng/g lw)> ?PCBs (15-90 ng/g lw)> ?PBDEs (1.5 68 ng/g lw). The major contributors were p,p'-DDE (median 44 ng/g lw), PCB 153 (2.3 ng/g lw), PCB 138 (2.1 ng/g lw), BDE 153 (1.2 ng/g lw) and BDE 47 (0.85 ng/g lw). Exposure to different OHCs between male and female donors was not significantly different (p > 0.05). However, ?PCBs and ?OHCs were significantly higher (p < 0.05) in diabetic donors than those of control group. We computed significantly positive correlations (p < 0.05) among different OHCs and between OHCs and age factor. The current study highlights the presence of different OHCs in humans from Jeddah, KSA. This is a preliminary study based on small sample size but our results suggested that detailed studies are required to understand the sources of these pollutants and their impact on human health. PMID- 26897297 TI - Evidence for spontaneous level-2 perspective taking in adults. AB - Social interactions are fostered by humans' propensity to compute their partner's perspective online. However, due to the mindreading system's limited capacity perspective taking (PT) was argued to occur spontaneously only for level-1, but not level-2 perspectives. We propose that level-2 perspectives (containing aspectual information) can also be computed spontaneously if participants have reason to assume that the partner is indeed aware of the objects' aspectual properties. Pairs of adult participants took part in the modified version of Surtees, Butterfill, and Apperly's (2012) number verification paradigm. Participants had prior information on their partner's task, which either called for processing aspectual properties or did not. The partner's inconsistent perspective was found to interfere with RT-s providing evidence for spontaneous level-2 PT. However, such interference only occurred when the partner's task involved processing the perspective dependent object feature, suggesting that PT was sensitive to the other's awareness of the to be represented information. PMID- 26897298 TI - Temporal focus, temporal distance, and mind-wandering valence: Results from an experience sampling and an experimental study. AB - When mind-wandering, people may think about events that happened in the past, or events that may happen in the future. Using experience sampling, we first aimed to replicate the finding that future-oriented thoughts show a greater positivity bias than past-oriented thoughts. Furthermore, we investigated whether there is a relation between the temporal distance of past- and future-oriented thoughts and the frequency of positive thoughts, a factor that has received little attention in previous work. Second, we experimentally investigated the relation between temporal focus, temporal distance, and thought valence. Both studies showed that future-oriented thoughts were more positive compared to past-oriented thoughts. Regarding temporal distance, thoughts about the distant past and future were more positive than thoughts about the near past and future in the experiment. However, the experience sampling study did not provide clear insight into this relation. Potential theoretical and methodological explanations for these findings are discussed. PMID- 26897299 TI - An anatomical study of the pathophysiology of carotid cavernous sinus fistula associated with Le Fort III osteotomy. AB - Carotid-cavernous sinus fistula (CCF) is a rare complication occurring after the Le Fort osteotomy. We aimed to elucidate the cause of CCF in the Le Fort osteotomy. METHODS: Eleven fresh cadavers were used. After craniotomy, a Le Fort III bipartition osteotomy was then performed. On the left side, both the lateral wall of the maxilla and the pterygomaxillary junction (PMJ) were divided, in addition to the conventional osteotomy line. On the right side, those parts were kept intact. After the osteotomy, a tensiometer was fixed to the skull base. The sensor was linked with the wall of the carotid artery in the cavernous portion. A down-fracture was then performed initially from the left, followed by the right. Tensile force data of both sides were recorded. RESULTS: In all cases, a higher tensile load was observed on the right side compared to the left side. In right side, two skull base fractures complexed with high pterygoid process fractures, and nine pure high fractures of the pterygoid process were identified. CONCLUSIONS: During down-fracture, the wall of the carotid artery experiences significant tensile load. The tensile load on the arterial wall may collapse the fine branches of the carotid artery in the cavernous portion. PMID- 26897300 TI - One stage treatment of temporomandibular joint complete bony ankylosis using total joint replacement. AB - INTRODUCTION: Temporomandibular joint ankylosis is a joint disorder due to bone or fibrous adhesion of the joint components that cause loss of function. There are many causes, such as trauma, infections and systemic diseases. To date, no uniform treatment protocol has been established. MATERIALS AND METHODS: We enrolled in the study patients that underwent single stage alloplastic total joint replacement for complete bony ankylosis. The subjective and objective variables were as follow: TMJ pain, diet, jaw function, quality of life, maximum interincisal opening (MIO) and occlusion. The minimum follow-up was 12 months. RESULTS: 12 patients met the inclusion criteria. Six patients underwent bilateral or monolateral total joint reconstruction with stock prosthesis, six patients underwent bilateral total joint reconstruction with custom made prosthesis. The mean preoperative MIO was 7.9 mm. The mean MIO reordered at 12-month follow-up was 26.5 mm (P < 0,0001). The occlusion was unchanged in 9 patients out of 12. In two patients the occlusion was changed by means of custom prosthesis design. In one patient occlusion worsened with less stable functional contact. Quality of life and diet relevantly improved in all cases. CONCLUSIONS: Single stage resection and reconstruction with total alloplastic TMJ reconstruction is an effective and reliable method to reestablish stable long-term mandibular function in ankylotic patients. PMID- 26897301 TI - Major factors contributing to anterior and posterior relapse after intraoral vertical ramus osteotomy. AB - The aim of this retrospective cohort study was to investigate the factors contributing to mandibular relapse after intraoral vertical ramus osteotomy (IVRO) while controlling for possible confounders. Forty-seven patients who underwent bimaxillary surgery were divided into three groups according to the direction of horizontal mandibular relapse: a stable group (group S), a posterior relapse group (group P), and an anterior relapse group (group A). Lateral cephalograms were analysed 1 month before and at 7 days and 12 months after surgery. One month before surgery, the pogonion in group A was positioned about 13 mm more anteriorly than in group P (P < 0.05). Immediately after surgery, the mandibles in groups A and S had moved about 6 mm more posteriorly than in group P. At 12 months, both the mandibles (point B) and the maxillae (point A) had moved posteriorly in group P (P < 0.05). A multivariate linear regression analysis showed that the amount of setback was the one key factor predicting postoperative mandibular changes 12 months after IVRO. As the amount of setback decreased, mandibular posterior horizontal relapse increased after IVRO. These findings suggest that the amount of setback can be a key factor predicting postoperative mandibular relapse. PMID- 26897302 TI - Lacerations and embedded needles due to EpiPen use in children. PMID- 26897303 TI - Risk Factors and Clinical Significance of Lymphopenia in Survivors of the Fontan Procedure for Single-Ventricle Congenital Cardiac Disease. AB - BACKGROUND: Congenital cardiac anomalies are associated with immunologic perturbations. Surgical thymectomy, thoracic duct manipulation, and protein- losing enteropathy (PLE), a condition related to stressed Fontan hemodynamics, presumably contribute to low peripheral absolute lymphocyte counts (ALCs) and quantitative immunoglobulins. Clinical significance of lymphopenia and hypogammaglobulinemia in single-ventricle survivors requires additional study. OBJECTIVE: Although immunologic laboratory anomalies are common in this population, we hypothesize that clinically significant immunodeficiency requiring intervention is rarely required. METHODS: A retrospective chart review of the immunologic parameters of patients enrolled in the Single Ventricle Survivorship Program (SVSP) at the Children's Hospital of Philadelphia was performed. RESULTS: The age range of the 178 SVSP patients was 3 to 26 years, with a median of 10.8 years. Most of the SVSP patients had some degree of lymphopenia. In the non-PLE group, the range of ALCs varied from 530 to 5322 cells/MUL, with 17 patients without PLE maintaining an ALC of less than 1000 cells/MUL. Among those with PLE, the median ALC and the IgG level were lower (672 cells/MUL and 200 mg/dL, respectively) than in those without (1610 cells/MUL and 868 mg/dL, respectively). Despite lymphopenia in the majority, few were severely clinically affected: 24% had delayed clearance of cutaneous viral infections, 63% had atopy, and 1 died of EBV-associated Hodgkin lymphoma. Immunoglobulin replacement was clinically indicated for 3 patients, 1 of whom had common variable immunodeficiency. Four patients with normal splenic function were treated with daily antibiotic prophylaxis. CONCLUSIONS: Patients with repaired single-ventricle physiology often demonstrate T-cell lymphopenia and hypogammaglobulinemia. A significant portion of patients without PLE also have lymphopenia. The most common clinical manifestation was delayed clearance of cutaneous viral infections, but significant systemic opportunistic infections were not seen despite laboratory abnormalities and lack of antimicrobial prophylaxis. PMID- 26897305 TI - Young children's referent selection is guided by novelty for both words and actions. AB - Young children are biased to select novel, name-unknown objects as referents of novel labels and to similarly favor novel, action-unknown objects as referents of novel actions. What process underlies these common behaviors? In the case of word learning, children may be driven by a novelty bias favoring novel objects as referents. Our study investigated this bias further by investigating whether novelty also affects children's selection of novel objects when a new action is given. In a pre-exposure session, 40 3- and 4-year-olds were shown eight novel objects for 1 min. In subsequent referent selection trials, children were shown two pre-exposed objects and one super-novel object and either heard a novel name or saw a novel action. The super-novel object was selected significantly more than the pre-exposed objects on both word and action trials. Our data add to the growing literature suggesting that an endogenous attentional bias to novelty plays a role in children's referent selection and demonstrates further parallels between word and action learning. PMID- 26897304 TI - Clinical Application of Nasal Filters: An Observational Study on the Usability of Nasal Filters in Managing Seasonal Allergic Rhinitis. AB - BACKGROUND: A recent park study found a substantial preventive effect of a new nasal filter for seasonal allergic rhinitis. However, the nasal filter still needs to prove that it is sufficiently convenient and comfortable for everyday use during a regular pollen season. OBJECTIVE: The objective of this study was to evaluate the usability of the nasal filter (Rhinix, Rhinix ApS, Aarhus, Denmark) in a large population. METHODS: An observational, open-label study (NCT02108379) conducted during the main grass pollen season in 2014 in Denmark included 1073 participants with seasonal allergic rhinitis, with or without asthma. Participants received the filters for a 2-week use period. Identical online questionnaires were answered after each week of use. End points included ratings on satisfaction, usage, and interest in continued use, stratified by allergy and asthma severity. RESULTS: There were 834 filter users in week 1; 634 of these continued use in week 2. After week 1, 630 (76%) expressed interest in continued use of the filters. Participants who continued use in week 2 had higher screening scores for nasal symptoms (P = .01), had more severe asthma for those with asthma (P = .04), and were more dissatisfied with their usual treatment compared with the participants who discontinued use (P = .03). CONCLUSIONS: Of 834 new users, 630 stated interest in continued use of the filters. On the basis of the findings of this large observational usability study, the nasal filters appear sufficiently convenient and comfortable to use and thus clinically relevant for symptom management for many allergy sufferers. PMID- 26897306 TI - Synchronous Pneumatocele and Organizing Pneumonia in the Course of a Staphylococcus aureus Infection. PMID- 26897307 TI - Pauci-immune crescentic glomerulonephritis without ANCA in a patient presenting with Candida parapsilosis endocarditis. PMID- 26897308 TI - Healthcare-associated infections due to carbapenemase-producing Enterobacteriaceae: Bacteriological profile and risk factors. PMID- 26897309 TI - Epidemiological and clinical characteristics of neurobrucellosis case patients in Tunisia. AB - OBJECTIVE: We aimed to identify epidemiological, clinical, therapeutic, diagnostic, and outcome characteristics of neurobrucellosis case patients in Tunisia. PATIENTS AND METHODS: We conducted a retrospective and descriptive study over a 17-year period (January 1997-December 2013). We included all neurobrucellosis patients hospitalized in the infectious disease department of La Rabta Hospital of Tunis during the study period. RESULTS: A total of 13 patients were included in the study: 9 men and 4 women. Mean age was 31.6 years. Six patients presented with meningitis, three with encephalitis, two with meningoencephalitis, and two with meningo-myeloradiculitis. All patients had a lumbar puncture performed. Eleven patients had an abnormal cerebrospinal fluid (CSF) (84.6%): lymphocytic pleocytosis in seven patients, high level of CSF proteins in 11, and low level of CSF glucose in seven. All patients had a positive Brucella serological test in blood. A Brucella serological test was also performed in CSF and was positive for 10 patients (77%). A total of nine patients had a cerebral CT scan and/or MRI performed and abnormalities were observed in six patients. Antibiotic therapy was prescribed to all patients: a combination of rifampicin and co-trimoxazole (n=9) or doxycycline (n=4) for an average duration of eight months. Two patients also received steroids. A positive outcome was observed in 10 patients. Three patients were lost to follow up. CONCLUSION: Brucellosis may be severe when neurological involvement occurs. Brucellosis should be considered in the event of any neurological involvement associated with suggestive epidemiological features. PMID- 26897310 TI - Outcomes and radiographic findings of anatomic press-fit radial head arthroplasty. AB - BACKGROUND: Radial head arthroplasty (RHA) is a popular method of treatment for complex fractures of the radial head. The purpose of this study was to investigate patient outcomes and radiographic findings associated with a single anatomic monopolar press-fit radial head system commonly used for the treatment of radial head fractures. METHODS: A retrospective review of prospectively collected data was performed for a consecutive series of patients treated with a press-fit anatomically designed RHA between November 2007 and April 2014. The most recent radiographs were evaluated for loosening, stress shielding, and instability. Postoperative motion and outcomes were reported at most recent follow-up. RESULTS: At an average follow-up of 30 months, 6 of the 15 patients (40%) demonstrated radiographic loosening. Six of the 9 patients (67%) without loosening demonstrated stress shielding (average, 6 mm). Functional outcome scores included a mean American Shoulder and Elbow Surgeons score of 70, Mayo Elbow Performance Score of 85, visual analog scale score for pain of 2, visual analog scale score for function of 7, and Single Assessment Numeric Evaluation score of 75. Average flexion-extension arc was 14 degrees to 138 degrees , and average pronation-supination was 75 degrees to 74 degrees . All 6 of the patients with radiographic loosening had undergone RHA with an associated ligamentous injury repair. Satisfaction among patients was high as no patient reported an unsatisfactory outcome. CONCLUSIONS: The use of an anatomic, press fit monopolar RHA in the management of acute complex radial head fractures has yielded excellent clinical outcomes despite high rates of radiographic loosening and stress shielding. Press-fit RHA in the setting of ligamentous injury warrants further investigation because of a high rate of implant loosening observed. PMID- 26897311 TI - Radiographic evaluation of short-stem press-fit total shoulder arthroplasty: short-term follow-up. AB - BACKGROUND: Humeral loosening is an uncommon etiology for revision shoulder arthroplasty. We aimed to evaluate the radiographic and clinical outcomes of a short-stem press-fit humeral component after primary total shoulder arthroplasty. METHODS: We reviewed our patient database, from January 2008 to December 2011, for primary total shoulder arthroplasties performed with a short-stem press-fit humeral component. Radiographs and clinical outcomes were evaluated in the immediate postoperative period and at the most recent follow-up, with at least 24 months of data for all patients. RESULTS: There were 73 shoulders that met our inclusion criteria, but 4 underwent revision before 2 years' follow-up. Only 1 of these 4 was revised for aseptic humeral loosening. Sixty-nine shoulders had at least 24 months of radiographic follow-up, and 62 had radiographic and clinical follow-up. Of the 69 shoulders, 5 underwent revision for humeral loosening: 1 for aseptic loosening and 4 for infection. Two other shoulders with humeral loosening were asymptomatic, and the patients refused revision surgery. The overall revision rate for humeral loosening was 8.2% (6 of 73 shoulders). Radiolucent zones of any size were seen in 71.0%, with 8.7% of these shoulders identified as having humeral stems at risk of future loosening. Significant improvements were made in most of the measured clinical outcomes. CONCLUSIONS: A high percentage of radiolucency was seen around the short-stem press-fit humeral components evaluated in this study at short-term follow-up. The overall rates of loosening and revision for the humeral implant examined in this study are higher than those noted in other recent studies evaluating press-fit stems. The cause of radiolucency and humeral loosening for this implant is not fully understood. PMID- 26897312 TI - Outcomes of reverse total shoulder arthroplasty as primary versus revision procedure for proximal humerus fractures. AB - BACKGROUND: Reverse total shoulder arthroplasty (RTSA) has been shown to be an effective treatment for proximal humerus fracture (PHF). This study evaluates outcomes of all patients with PHF treated with RTSA as a primary procedure for acute PHF, a delayed primary procedure for symptomatic PHF malunion or nonunion, a revision procedure for failed PHF hemiarthroplasty (HA), or a revision procedure for failed open reduction and internal fixation (ORIF). METHODS: Patients who underwent RTSA for PHF were evaluated for active range of motion and Shoulder Pain and Disability Index (SPADI), Simple Shoulder Test-12, American Shoulder and Elbow Surgeons (ASES), University of California-Los Angeles (UCLA) shoulder rating scale, Constant, and 12-Item Short Form Health Survey scores. Scaption and external rotation (ER) strength were also assessed. RESULTS: RTSA was performed in 49 patients with PHF; 13 patients underwent RTSA for acute PHF, 13 for malunion or nonunion, 12 for failed PHF HA, and 11 for failed PHF ORIF. ER range of motion, SPADI, ASES, UCLA, and Constant scores achieved significance. The acute fracture group significantly outperformed the failed HA group in SPADI, ASES, and UCLA scores. The malunion/nonunion group significantly outperformed the failed HA group in ASES and UCLA scores. The acute fracture and malunion/nonunion groups each had significantly greater ER than the failed HA group. CONCLUSION: RTSA is an effective treatment option for PHF as both a primary and a revision procedure. Primary RTSA outperformed RTSA done as a revision procedure. RTSA for acute PHF is comparable to RTSA for malunions and nonunions. Our outcomes of revision RTSA for failed HA and ORIF are more promising than previously published. PMID- 26897313 TI - Does immediate elbow mobilization after distal biceps tendon repair carry the risk of wound breakdown, failure of repair, or patient dissatisfaction? AB - BACKGROUND: Rehabilitation protocols after distal biceps repair are highly variable, with many surgeons favoring at least 2 weeks of immobilization. Is this conservative approach necessary to protect the repair? METHODS: This was a consecutive series of 22 distal biceps tendon repairs in which a cortical button system was used. Patients were encouraged to mobilize their elbow actively from the day of surgery. Physiotherapy commenced at 3 weeks, with strengthening exercises when full range of movement (ROM) was achieved. The primary outcome measured was the clinical integrity of the repaired tendon. Secondary outcomes comprised wound or nerve complication, elbow ROM, and patient-reported outcome measures (the 11-item version of the Disabilities of Arm, Shoulder and Hand, Mayo Elbow Performance Index, and Oxford Elbow Score). RESULTS: All patients were male, and the dominant arm was repaired in 60%. Mean age was 40.6 years (range, 27-62 years), and mean time to surgery was 17 days (range, 5-99 days). Mean follow-up was 16.6 months (range, 3.8-29 months). All tendons were clinically intact at time of review. No wound breakdown occurred. Mean extension was -6 degrees (range, -10 degrees to 10 degrees ), and flexion was 144 degrees (range, 135 degrees -150 degrees ). All patients achieved full pronosupination. ROM was equivalent to the uninjured arm (P = .7). The mean 11-item version of the Disabilities of Arm, Shoulder and Hand score was 2.7 (range, 0-15.9), the Mayo Elbow Performance Index was 97.8 (range, 70-100), and the Oxford Elbow Score was 46.9 (range, 43-48) at the latest follow-up. One-third of patients experienced a transient sensory neurapraxia. CONCLUSION: Immediate mobilization after biceps tendon repair with a cortical button is possible, and in this series was not associated with failure of the repair, wound breakdown, or patient dissatisfaction. However, this series emphasizes the high incidence of nerve complication that can be associated with the single transverse incision technique. PMID- 26897314 TI - Biologic resurfacing arthroplasty with acellular human dermal allograft and platelet-rich plasma (PRP) in young patients with glenohumeral arthritis-average of 60 months of at mid-term follow-up. AB - BACKGROUND: The treatment of young patients with glenohumeral arthritis has been challenging. Alternative treatment options include activity modification, arthroscopic debridement, and arthroplasty. Addressing the glenoid during arthroplasty in this population of patients continues to be a significant challenge. In this study, we evaluated the midterm outcomes of hemiarthroplasty with biologic resurfacing of the glenoid with human dermal matrix allograft. METHODS: Between 2004 and 2011, 55 patients underwent hemiarthroplasty and biologic resurfacing of the glenoid with human dermal matrix allograft. The average age was 50 +/- 9 years. Subjective evaluation was performed with the Western Ontario Osteoarthritis of the Shoulder Index, American Shoulder and Elbow Surgeons score, visual analog scale, and Single Assessment Numeric Evaluation. Patients returned to the clinic for clinical examination and radiographic evaluation. The average follow-up was 60 months. RESULTS: The average postoperative American Shoulder and Elbow Surgeons score was 76 +/- 22, and the Western Ontario Osteoarthritis of the Shoulder Index score was 76% +/- 22%. The visual analog scale score was 2.4 +/- 2.6. The average preoperative Single Assessment Numeric Evaluation score was 33% +/- 22%, which significantly improved to 72% +/- 22% postoperatively. Eighty-one percent of the patients were satisfied (10/47) or highly satisfied (28/47) with their result. With radiographic evaluation, the average joint space was 1 +/- 1 mm preoperatively and 2 +/- 1 mm postoperatively. A total of 5 cases (9.1%) were revised to anatomic total shoulder arthroplasty with implantation of a glenoid component. DISCUSSION: Hemiarthroplasty with biologic resurfacing of the glenoid using human dermal matrix allograft can lead to successful midterm outcomes with satisfactory complication and revision rates. Both patient satisfaction and clinical outcome remain high regardless of radiographic outcome. PMID- 26897315 TI - Bennett lesions in baseball players detected by magnetic resonance imaging: assessment of association factors. AB - BACKGROUND: The purpose of this study was to evaluate the characteristics of Bennett lesions in baseball players compared with those without a Bennett lesion and to identify other possible factors associated with Bennett lesions on magnetic resonance imaging (MRI). METHODS: We investigated 388 male baseball players with a career >1 year. Demographic factors and a routine physical examination, including glenohumeral internal rotation difference, scapular dyskinesis, and various pathologic changes, were reviewed on MRI to identify relative factors for Bennett lesions. RESULTS: Of the 388 patients evaluated, 125 (32.2%) were diagnosed with Bennett lesions of the shoulder. No significant differences were observed between the groups in demographic factors, physical examination results, visual analog scale score, American Shoulder and Elbow Surgeons score, or prevalence of concomitant diseases. However, players with Bennett lesions had played baseball longer than those without the lesions (P < .001). CONCLUSION: An association was found between Bennett lesions and the length of time that a patient with a Bennett lesion had played baseball. The prevalence of pathologic lesions detected on MRI and the physical examination results were not different between players with and without Bennett lesions. PMID- 26897316 TI - Biomechanical effects of rotator interval closure in shoulder arthroplasty. AB - BACKGROUND: Subscapularis dysfunction remains a significant problem after shoulder arthroplasty. Published techniques have variable recommendations for placing a rotator interval closing suture in attempts to off-load the subscapularis repair site, the implications of which have yet to be examined in the literature. The goals of this study were to investigate the biomechanical benefit of the rotator interval closing suture on the subscapularis repair strength and to analyze the effect on shoulder range of motion. METHODS: Sixteen matched cadaveric shoulders underwent a subscapularis tenotomy and shoulder arthroplasty. The subscapularis tenotomy was repaired, and motion at physiologic torsional force was recorded. One of each matched pair was randomly assigned to receive an additional rotator interval closure suture. Each specimen then underwent a standardized cyclic loading with measurement of gap formation and load to failure. RESULTS: The rotator interval closing suture significantly increased the ultimate load to failure of the subscapularis repair (452 N vs. 219 N; P = .002) and decreased gap formation at the subscapularis repair site. Measurement of the shoulder motion showed no significant difference between shoulders with and without the rotator interval closing suture. DISCUSSION: We report the additional biomechanical benefit that the rotator interval closing suture provides to the subscapularis repair site after shoulder arthroplasty. This suture acts to improve the load to failure of the subscapularis repair and to decrease gap formation under cyclic load. Furthermore, it does not detrimentally affect shoulder external rotation or overall arc of rotation. Our findings support the application of this off-loading technique after subscapularis repair during shoulder arthroplasty. PMID- 26897317 TI - Comparison of satisfied and dissatisfied patients 2 to 5 years after anatomic total shoulder arthroplasty. AB - BACKGROUND: With an increasingly large number of patients undergoing total shoulder arthroplasty (TSA) combined with increased requirements for public reporting of patient outcomes, there is a greater need to better understand the underlying factors related to patient satisfaction. The purpose of this study was to compare patient demographics, nonorthopedic comorbidities, patient-reported outcome scores, and range of motion of patients who reported being either satisfied or dissatisfied with their procedure at midterm follow-up. METHODS: We identified 234 primary TSAs performed by a single surgeon for glenohumeral osteoarthritis with a minimum 2-year follow-up in a prospective shoulder arthroplasty registry. American Shoulder and Elbow Surgeons (ASES) score, patient satisfaction, and active forward flexion, abduction, and external rotation at 0 degrees of flexion-abduction were assessed before and after TSA. RESULTS: Of the 234 patients, 207 (88.5%) were satisfied with their procedure. Dissatisfied patients had significantly lower ASES scores both before and after surgery (P < .001) as well as a significantly lower preoperative to postoperative change in ASES score (P < .001). Similarly, dissatisfied patients demonstrated significantly lower changes in active forward flexion (P = .004), abduction (P = .02), and external rotation (P = .03). Patients with ASES score changes <12 points were 19 times more likely to be dissatisfied after TSA (95% confidence interval, 4.4-81.4; P = .0001). CONCLUSION: Dissatisfied patients had significantly lower improvements in pain, function, and range of motion. Furthermore, a change in ASES score <12 points was associated with a 19-fold increase in the risk of being dissatisfied after TSA. PMID- 26897318 TI - An academic-VA partnership: Student interprofessional teams integrated with VA PACT teams. AB - Veterans are challenged with multiple unique healthcare issues related to their military service environment. Likewise, health care providers must understand the special concerns associated with military conflict and recognize how the veteran's care can be optimized by interprofessional care delivery. Little is taught didactically or clinically that supports nursing students in addressing the unique issues of the veteran or the student's need to work collaboratively with allied health team members to enhance the veteran's care. Because of limited exposure to the veteran's special conditions, nursing students who may seek a career with the veteran population often face challenges in rendering appropriate care. The VA offers an invaluable opportunity for health profession students to collaborate with VA interprofessional Patient Aligned Care Teams (PACT) ultimately optimizing veteran health outcomes. This academic partnership, that implements an interprofessional model, will prepare students to better embrace the veteran population. This article describes the immersion of health profession students in interprofessional collaborative practice (IPCP) using PACT team principles which ultimately promotes the students' ability to link theory content to patient care delivery. PMID- 26897319 TI - Outcome of the Joint Council of Thoracic Surgery Education's Early Review Course Project. AB - BACKGROUND: The Joint Council on Thoracic Surgical Education was formed in 2008 to improve cardiothoracic education. Resident learning has been a concern as reflected in declining passing rates on the American Board of Thoracic Surgery examinations. The Joint Council on Thoracic Surgical Education piloted a program to determine whether early exposure to a cardiothoracic curriculum through participation in a board review course would improve learning. The purpose of this paper is to report the results of this project. METHODS: Residents from the incoming classes of traditional 5-2 or 5-3 cardiothoracic training programs were randomly selected to attend a 3-day board review course (University of Utah) in September of their first year. For the 2012 and 2013 classes of cardiothoracic residents, we asked all incoming residents to take the prior spring in-training examination in July of their first year and then take the in-training examination in the spring of their first year. We combined the results of the incoming class of 2012 and 2013 and analyzed the results. RESULTS: There were 171 residents who participated in either 2012 or 2013. There were 38 residents (78.9% were men) who attended the board review course and 133 (79.7% men) who did not. Questionnaires completed by the program directors and the residents who took the review course showed a favorable opinion of the program. The number of correct answers on the in-training examination, the percentage correct, and the percentile rank score increased more for the residents who took the review course, but was not statistically significant. When only the general thoracic surgery questions were analyzed, there was a statistically significant increase in the rank change between residents who attended the review course and residents who did not (8.4% increase versus 2.0% decrease, respectively; p = 0.042, Student t test). CONCLUSIONS: This pilot study established for the first time the baseline level of knowledge of incoming residents assessed by the in-training examination. Participation in a board review type course early in the residency training program may increase learning by cardiothoracic residents, but there was not a clear statistical difference between the two groups. The program was viewed as favorable by both the participating residents and the program directors. PMID- 26897320 TI - Surgical Intervention for Anomalous Origin of Left Coronary Artery From the Pulmonary Artery in Children: A Long-Term Follow-Up. AB - BACKGROUND: Anomalous left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital heart defect with limited data on long-term outcomes after surgical intervention. METHODS: We conducted a retrospective review of all children (N = 42) who underwent surgical repair of ALCAPA between 1980 and 2014 at the Royal Children's Hospital, Melbourne. RESULTS: Twenty-nine (69% [29 of 42]) patients underwent coronary reimplantation, 12 (29% [12 of 42]) had intrapulmonary baffle (Takeuchi) repair, and 1 (2% [1 of 42]) patient had ligation of the anomalous coronary artery. Nine (21%, 9 of 42) patients had concomitant mitral valve (MV) repair at the time of ALCAPA repair. A left ventricular assist device (LVAD) was used in 36% (15 of 42) of patients. Early mortality was 2.4% (1 of 42 patients). Median follow-up was 14 years (mean, 13 years; range, 4 months-31 years). There were no late deaths. Survival was 98% at 20 years. Freedom from reoperation was 81%, 81%, and 76% at 5, 10, and 20 years after operation, respectively. Eight patients underwent late MV repair or replacement at a median of 3 years (mean, 8 years; range, 2 months-25 years) after operation. Freedom from late MV repair or replacement was 86% at 5 and 10 years and 81% at 20 years after operation. Eleven (26% [11 of 42]) patients had severe mitral regurgitation (MR) preoperatively. Of those 11 patients, 5 (45% [5 of 11]) had concomitant MV repair at the time of ALCAPA repair, 3 (27% [3 of 11]) had late MV repair or replacement, and the remaining 3 (27% [3 of 11]) patients had mild MR at last follow-up. Thirty-six (90% [36 of 41]) patients had normal left ventricular function and 4 (10% [4 of 41]) patients had mildly reduced left ventricular (LV) function at last follow-up. CONCLUSIONS: ALCAPA can be operated on with good outcomes. Persistent MR and a moderate rate of late MV repair warrants close follow-up. PMID- 26897321 TI - A Single-Institution Analysis of the Surgical Management of Pulmonary Large Cell Neuroendocrine Carcinomas. AB - BACKGROUND: Large cell neuroendocrine carcinoma (LCNEC) is an uncommon tumor of the lung and represents approximately 3% of all lung cancers. LCNEC displays biological behaviors resembling those of small cell lung carcinomas and features of high-grade neuroendocrine tumors. LCNEC of the lung are considered aggressive. Reported prognoses are heterogeneous, and the optimum treatment remains undefined. METHODS: We conducted a retrospective study of all patients who were treated for LCNEC in our Department of Thoracic Surgery between May 2005 and December 2013. Primary outcomes of interest were patient survival and prognostic factors. Kaplan-Meier analysis was performed to determine the significant predictors of overall survival. RESULTS: Within the prescribed period, 127 patients were treated for LCNEC, and 125 underwent surgical resection with curative intent. Induction chemotherapy or radiochemotherapy was given to 9 patients, and 63 patients received postoperative chemotherapy. Complete resection was achieved in 99.2%. The overall 1-, 3- and 5-year survival rates were 83.7%, 63.2%, and 53.8% of all patients, and the 5-year survival in patients at stages I, II, and III was 64.5%, 40%, and 29.7%. There was a significant survival difference at 5 years between pT1/2 (58.5%) and pT3 tumors (22.4%; p = 0.043) and for patients with lymphatic involvement (L0 vs L1, p = 0.001; pN1 or pN2 vs pN0, p = 0.04). CONCLUSIONS: Surgical treatment can achieve satisfactory results in early tumor stages, which are comparable with other non-small cell lung cancers, with a low perioperative mortality rate. PMID- 26897322 TI - Transvenous Implantation of a Stent Valve in Patients With Degenerated Mitral Prostheses and Native Mitral Stenosis. AB - BACKGROUND: The purpose of this study was to report the use of a transvenous transseptal approach using a stent valve in patients with degenerated biological mitral valve prostheses, regurgitation after mitral repair, and native mitral stenosis. METHODS: Ten patients (median age, 74 years; range, 20-89 years; 5 men and 5 women) with degenerated mitral bioprosthetic valves (n = 7), failed mitral repair (n = 1), or calcified native stenotic valves (n = 2) underwent transvenous implantation of a stent valve. RESULTS: The procedure was initially successful in all patients. Predilation was performed for balloon sizing only in the 2 patients with native mitral stenosis. The stent valve was deployed during 1 period of rapid pacing. A guidewire, as a loop from the right femoral vein and through the left ventricular apex, facilitated a good angle and secure positioning of the stent valve. An ultrasonographically guided puncture of the apex was carried out in 6 patients, and in the other 4 we performed a minithoracotomy before apical puncture. All valves were implanted in a good position with improved function and without significant paravalvular leakage (PVL). There were no periprocedural deaths. The 30-day survival was 80% (8 of 10 patients), and 60% (6 of 10) of patients were still alive a median time of 290 days after the procedure. CONCLUSIONS: Transvenous transseptal implantation of a stent valve was performed in 10 patients with mitral valve disease, with good early functional results. These high-risk patients must be carefully selected by a multidisciplinary team because the procedure carries a high mortality. PMID- 26897323 TI - Thoracoscopic Mesh Repair of Diaphragmatic Defects in Hepatic Hydrothorax: A 10 Year Experience. AB - BACKGROUND: The objective was to analyze the outcomes of thoracoscopic mesh repair for hepatic hydrothorax (HH) at our institution during the past 10 years. METHODS: A total of 63 patients with refractory HH who underwent thoracoscopic mesh onlay reinforcement to repair diaphragmatic defects from January 2005 to December 2014 were included in the study. Mesh covering alone was used in 47 patients and mesh with suturing was used in 16 patients. Patient demographics, Child-Pugh class, and model for end-stage liver disease (MELD) score were evaluated to predict morbidity and mortality. RESULTS: Of the patients (mean age, 60.4 +/- 15 years; 31 men and 32 women), 14.3% had concomitant underlying diseases of renal insufficiency, 34.9% had diabetes mellitus, and 4.8% had pneumonia. Diaphragmatic blebs were the most common diaphragmatic defects (29 of 63 [46%]). After a median 20.5 months of follow-up examinations, 4 patients experienced recurrence. The 1-month mortality rate was 9.5% (6 of 63 patients). On multivariable analysis, underlying impaired renal function (p = 0.039) and MELD scores (p = 0.048) were associated with increased 3-month mortality in 16 patients. Contrary to the rising Child-Pugh score (p = 0.058), rising MELD scores represented an increase in kidney or liver failure and mortality. The main causes of 3-month mortality were septic shock (n = 6), acute renal insufficiency (n = 4), gastrointestinal bleeding (n = 4), hepatic encephalopathy (n = 1), and ischemic bowel (n = 1). CONCLUSIONS: Thoracoscopic mesh repair for refractory HH improves symptoms and lowers the recurrence rate. PMID- 26897324 TI - Ninety-day perioperative complications of pediatric robotic urological surgery: A multi-institutional study. AB - BACKGROUND: Robotic technology is the newest tool in the armamentarium for minimally invasive surgery. Individual centers have reported on both the outcomes and complications associated with this technology, but the numbers in these studies remain small, and it has been difficult to extrapolate meaningful information. OBJECTIVES: The intention was to evaluate a large cohort of pediatric robotic patients through a multi-center database in order to determine the frequency and types of complications associated with robotic surgery for pediatric reconstructive and ablative procedures in the United States. STUDY DESIGN: After institutional review board approvals at the participating centers, data were retrospectively collected (2007-2011) by each institute and entered into a RedCap((r)) database. Available demographic and complication data that were assigned Clavien grading scores were analyzed. RESULTS: From a cohort of 858 patients (880 RAL procedures), Grade IIIa and Grade IIIb complications were seen in 41 (4.8%); and one patient (0.1%) had a grade IVa complication. Intraoperative visceral injuries secondary to robotic instrument exchange and traction injury were seen in four (0.5%) patients, with subsequent conversion to an open procedure. Grade I and II complications were seen in 59 (6.9%) and 70 (8.2%) patients, respectively; they were all managed conservatively. A total of 14 (1.6%) were converted to an open or pure laparoscopic procedure, of which, 12 (86%) were secondary to mechanical challenges. DISCUSSION: It is believed that this study represents the largest and most comprehensive description of pediatric RAL urological complications to date. The results demonstrate a 4.7% rate of Clavien Grade IIIa and Grade IIIb complications in a total of 880 cases. While small numbers make it difficult to draw conclusions regarding the most complex reconstructive cases (bladder diverticulectomy, bladder neck revision, etc.), the data on the more commonly performed procedures, such as the RAL pyeloplasty and ureteral reimplantation, are robust and more likely represent the true complication rate for these procedures when performed by highly experienced robotic surgeons. CONCLUSION: Pediatric robotic urologic procedures are technically feasible and safe. The overall 90-day complication rate is similar to reports of laparoscopic and open surgical procedures. COMPLICATIONS: n (%) Life threatening (IVa): 1 (0.1%) Requiring radiologic and or surgical intervention (IIIa and IIIb): 41 (4.8%) Secondary to robotic system: 4 (0.5%) Mechanical failure leading to conversion: 14 (1.6%). PMID- 26897326 TI - Young rats exhibit an age- and sex-dependent bladder response to alpha antagonists but not beta-agonists. AB - INTRODUCTION: Previous studies have suggested that the onset of alpha- (alpha) and beta- (beta) adrenergic receptor activity is delayed in young animals. The use of alpha1- (alpha1-) antagonists for dysfunctional voiding, and beta3- (beta3 ) agonists for overactive bladder in younger children may not be indicated if maturation is required before bladder and urethral adrenergic receptors are active. OBJECTIVE: To determine the sex- and age-dependent responses of the bladder and external urethral sphincter (EUS) to alpha- and beta-adrenergic agents in neonatal and young adult rats. MATERIALS AND METHODS: A total of 72 naive Sprague-Dawley rats (36 female, 36 male) and 15 bladder-reduced (BR) female Sprague-Dawley rats underwent cystometry and EUS electromyography at 3, 6, and 9 weeks of life. Following administration of WAY 100,635 (0.3 mg/kg, serotonergic receptor antagonist), the non-selective alpha-agonist phenylephrine (0.3 mg/kg), alpha-antagonist phentolamine (1-3 mg/kg), beta-agonist isoprenaline (3 mg/kg) and beta-antagonist propranolol (3 mg/kg) were delivered intravenously. The maximum intravesical pressure (IVP), pressure threshold (PT), intermicturition interval (IMI), contraction duration (CD), burst amplitude and burst frequency were compared after each drug. RESULTS: The alpha-antagonist phentolamine lowered the IVP in 9-week-old males without lowering the PT. In contrast, the beta agonist isoprenaline lowered the IVP in both males and females of all ages, also without affecting the PT. Isoprenaline was also effective at shortening the CD in females, suggesting more effective bladder emptying. The alpha-agonist phenylephrine increased the IVP in 3-week-old and 6-week-old females and 3-week old males, but this effect was blocked by pretreatment with phentolamine. The beta-antagonist propranolol increased the PT in both males and females, and shortened the IMI in females, which was consistent with retention. Phenylephrine increased the burst duration in 9-week-old naive females, while isoprenaline increased the burst amplitude and duration in 9-week-old BR females. CONCLUSIONS: In the neonatal rat, both alpha- and beta-adrenergic receptors actively regulate bladder function by 3 weeks of life, but the desired effect of decreasing IVP by alpha-antagonists was delayed until 9 weeks in male rats. In contrast, beta agonists were effective at decreasing IVP in both male and female rats of all ages, which suggests that they are better agents for enhancing bladder emptying in female and young male rats. PMID- 26897327 TI - The use of intermittent trunk flexion to alleviate low back pain during prolonged standing. AB - The current study examined of the effect of intermittent, short-term periods of full trunk flexion on the development of low back pain (LBP) during two hours of standing. Sixteen participants completed two 2-h standing protocols, separated by one week. On one day, participants stood statically for 2h (control day); on the other day participants bent forward to full spine flexion (termed flexion trials) to elicit the flexion relaxation (FR) phenomenon for 5s every 15min (experimental day). The order of the control and experimental day was randomized. During both protocols, participants reported LBP using a 100mm visual analogue scale every 15min. During the flexion trials, lumbar spine posture, erector spinae and gluteus medius muscle activation was monitored. Ultimately, intermittent trunk flexion reduced LBP by 36% (10mm) at the end of a 2-h period of standing. Further, erector spinae and gluteus medius muscle quietening during FR was observed in 91% and 65% of the flexion trials respectively, indicating that periods of rest did occurred possibly contributing to the reduction in LBP observed. Since flexion periods do not require any aids, they can be performed in most workplaces thereby increasing applicability. PMID- 26897325 TI - Sacral agenesis and neurogenic bladder: Long-term outcomes of bladder and kidney function. AB - BACKGROUND: Sacral agenesis (SA) is a rare congenital condition that refers to the absence of part or all of two or more lower sacral vertebral bodies. It can be associated with neurogenic bladder dysfunction that does not necessarily correlate with the level of spinal or skeletal defect. Patients with SA should undergo urodynamic studies (UDS) to guide lower urinary tract (LUT) management. OBJECTIVE: This review aimed to update the present institutional experience since 1981 of this rare patient population with detailed, long-term follow-up of bladder and kidney function. STUDY DESIGN: A single institution, retrospective, IRB-approved review was performed on patients born after January 1, 1981 with an isolated diagnosis of sacral agenesis without spina bifida, and followed with urologic involvement at Boston Children's Hospital. Records were reviewed for demographics, radiologic imaging, UDS including cystometrogram (CMG) and electromyography (EMG), surgery, and blood chemistries. Comparisons were made between groups of patients based on age at diagnosis, with specific focus on renal function and stability of neurogenic bladder lesion. RESULTS: Forty-three patients were identified: 23 female and 20 male. Thirty-seven children (86%) had a known age of diagnosis. Nineteen were diagnosed before 2 months old, including five who were diagnosed prenatally, 11 were diagnosed between 2 and 18 months, and seven were diagnosed after 18 months. All 43 had UDS, with 24 (55.8%) studied at the time of diagnosis (Summary Table). Twenty had serial full UDS, with 30% demonstrating neurourologic instability. None developed end-stage renal disease (ESRD) or required spinal cord detethering. DISCUSSION: Many children with SA appeared to be diagnosed prenatally or early in life; SA was mostly identified during evaluation of associated anomalies. Though UDS aid in urologic management, testing was not routinely utilized at the time of diagnosis. CONCLUSIONS: This review of long-term follow-up in SA patients showed stable LUT and renal function, with minimal risk of progression to ESRD. PMID- 26897328 TI - The use of piezoelectric surgery to lateralize the inferior alveolar nerve with simultaneous implant placement and immediate buccal cortical bone repositioning: a prospective clinical study. AB - A prospective study was conducted to assess a variation of inferior alveolar nerve (IAN) lateralization. This study included 13 patients. An osteotomy was made with a piezoelectric device, and the IAN bundle was moved buccally. Dental implants were then inserted medial to the nerve bundle, and the inner surface of the buccal cortical bone plate was shaped to reduce its thickness. Finally, the bone plate was repositioned to restore the original shape and contour of the mandible. Neurosensory examinations of the lower lip and chin were performed using three tests: light touch, pain, and two-point discrimination. Three months after surgery, the function of the IAN was judged to be completely restored at 11 of the 13 surgical sites. Differences in the tests comparing the operated and non operated sides were not significant. No implants were lost, and all patients were satisfied with the result. Although IAN lateralization in conjunction with dental implant placement is rarely indicated, the use of a piezoelectric device to perform a buccal osteotomy with final repositioning of the buccal cortical plate over the bony defect contributes to the recovery of the contour and shape of the mandible, without impairment of IAN function. PMID- 26897329 TI - Two sisters with macular dystrophy caused by the 3243A>G mitochondrial DNA mutation. AB - CASE REPORT: Two sisters of 54 and 60years old, with a history of diabetes and deafness, consulted for decreased visual acuity (VA). Funduscopic examination revealed patchy areas of chorioretinal atrophy with annular arrangement around the fovea. Genetic study identified the heteroplasmic mutation 3243A>G in mitochondrial DNA, which supports syndrome maternally inherited diabetes and deafness (MIDD) or Ballinger-Wallace disease. DISCUSSION: The finding of such macular disorders, especially in the presence of diabetes mellitus and deafness, should suggest the performing of a mitochondrial genome screening to identify this unusual syndrome. PMID- 26897330 TI - Contributions of "big data". PMID- 26897331 TI - Swept-Source optical coherence tomography... beyond the sclera. PMID- 26897332 TI - Usefulness of surgical complexity classification index in cataract surgery process. AB - OBJECTIVE: To evaluate the usefulness of surgical complexity classification index (SCCI) to predict the degree of surgical difficulty in cataract surgery. MATERIAL AND METHODS: This retrospective study includes data collected between January 2013 and December 2014 from patients who underwent cataract extraction by phacoemulsification at our hospital. A sample size of 159 patients was obtained by simple random sampling (P=.5, 10% accuracy, 95% confidence). The main variables were: recording and value of SCCI in electronic medical record (EMR), presence of exfoliation syndrome (XFS), criteria for inclusion in surgical waiting list (SWL), and functional results. SCCI was classified into 7 categories (range: 1-4) according to predictors of technical difficulty, which was indirectly estimated in terms of surgical time (ST). All statistical analyses were performed using SPSS v15.0 statistical software. RESULTS: Prevalence of XFS was 18.2% (95%CI: 11.9-24.5). In terms of quality indicators in the cataract surgery process, 96.8% of patients met at least one of the criteria to be included in SWL, and 98.1% gained >=2 Snellen lines. The SCCI was recorded in EMR of 98.1% patients, and it was grouped for study into 2 categories: High and low surgical complexity. Statistically significant differences in the distribution of ST were found depending on the assigned SCCI (P<.005) and the presence of XFS (P<.005). CONCLUSIONS: The SCCI enables to estimate the degree of surgical complexity in terms of ST in cataract surgery, which is especially useful in those areas with high prevalence of XFS, because of the higher theoretical risk of surgical complications. PMID- 26897333 TI - Mooren's ulcer: 30 years of follow-up. AB - CASE REPORT: A 33-year-old Caucasian female presented with epiphora, ocular pain, and foreign body sensation in both eyes for one month. Examination revealed bilateral peripheral corneal ulcers. The patient had been treated with immunomodulators, and she was treated in the left eye with peripheral semi circular keratoplasty, penetrating keratoplasty, conjunctival-corneal scleroplasty, buccal mucosal graft, tibial osteo-keratoprosthesis and finally, retinal detachment. DISCUSSION: Mooren's ulcer is an immunological corneal disease. This lesion must be treated initially with immunomodulators. Surgical treatment should be considered when a risk of corneal perforation is present, when the perforation appears, or under acute necrosis. PMID- 26897334 TI - Does change in microcalcifications with neoadjuvant treatment correlate with pathological tumour response? AB - AIM: To determine whether change in microcalcification density and extent after neoadjuvant treatment (NAT) can predict tumour response. MATERIALS AND METHODS: This single-institution, retrospective study included all women with breast cancer who underwent NAT between 1 January 2008 and 31 December 2014, and fulfilled the following criteria: mammography before NAT with pathological microcalcifications, mammography performed after NAT, and tumour resection at Tel Aviv Sourasky Medical Center. Correlation was made between mammography features and clinicopathological information. RESULTS: Fifty-four patients met the inclusion criteria. Post-NAT, the number of calcifications remained stable in 30 (55.5%) patients, decreased in 23 (42.6%) patients, and increased in one (1.9%) patient. Patients with a decreased number of malignant calcifications post-NAT had higher rates of pathological complete response compared to patients with no change (59% versus 20%, p=0.009). Patients with triple negative and human epidermal growth factor receptor 2 (HER2) receptor subtypes had higher rates of decreased number of calcifications post-NAT (50% versus 35%) and pathological complete response (57% versus 11%, p=0.007) compared to patients with luminal receptor subtype. In addition, patients who received a combination of chemotherapy and biological treatment had more cases of decreased number of calcifications compared to patients who received chemotherapy alone (56% versus 39%). No significant correlation was observed between calcification change post NAT and calcification morphology or distribution pattern. CONCLUSIONS: Patients with breast carcinoma and decreased number of pathological calcifications post NAT had higher rates of pathological complete response compared to patients with no change in calcifications; however, a substantial number of patients with complete pathological response had no change in microcalcification distribution with treatment, questioning the need to completely excise all calcifications post NAT. PMID- 26897335 TI - Challenges in contrast-enhanced spectral mammography interpretation: artefacts lexicon. AB - AIM: To review and describe commonly encountered artefacts in contrast-enhanced spectral mammography (CESM). MATERIALS & METHODS: This retrospective study included 200 women who underwent CESM examinations for screening and diagnostic purposes. Analysis was performed on the image data sets of these women, comprising of a total of 774 subtracted images. Images were reviewed with focus on the presence of four artefacts: rim ("breast within breast"), ripple (black and white lines), axillary line, and skin-line enhancement (skin-line highlighting). Statistical cross-correlation and association with acquisition parameters (tube current, tube voltage, compression force, breast thickness, paddle size) was compared using Fisher's exact test and t-test. RESULTS: The rim artefact was highly common (97-99%) in every projection. The ripple artefact was increasingly more common on the oblique projections (80-82%) and found to be associated with higher breast thickness values. The axillary line artefact was detected only on oblique projections (63%) and associated with the use of a small compression paddle. The skin-line enhancement artefact was seen in 19-46% of projections. None of the artefacts interfered with image interpretation. CONCLUSIONS: Two main artefacts commonly seen on CESM are rim and ripple artefacts. They do not hamper with image interpretation. It is important to be aware of them and prevent misinterpretation of these artefacts as real breast pathology. PMID- 26897336 TI - Nuclear medicine imaging of bone infections. AB - Osteomyelitis is a broad group of infectious diseases that involve the bone and/or bone marrow. It can arise haematogenously, via extension from a contiguous infection, or by direct inoculation during surgery or trauma. The diagnosis is not always obvious and imaging tests are frequently performed as part of the diagnostic work-up. Commonly performed radionuclide tests include technetium-99m ((99m)Tc)-diphosphonate bone scintigraphy (bone), and gallium-67 ((67)Ga) and in vitro labelled leukocyte (white blood cell; WBC) imaging. Although they are useful, each of these tests has limitations. Bone scintigraphy is sensitive but not specific, especially when underlying osseous abnormalities are present. (67)Ga accumulates in tumour, trauma, and in aseptic inflammation; furthermore, there is typically an interval of 1-3 days between radiopharmaceutical injection of and imaging. Currently, this agent is used primarily for spinal infections. Except for the spine, WBC imaging is the nuclear medicine test of choice for diagnosing complicating osteomyelitis. The in vitro leukocyte labelling process requires skilled personnel, is laborious, and is not always available. Complementary marrow imaging is usually required to maximise accuracy. Not surprisingly, alternative radiopharmaceuticals are continuously being investigated. Radiolabelled anti-granulocyte antibodies and antibody fragments, investigated as in vivo leukocyte labelling agents, have their own limitations and are not widely available. (111)In-biotin is useful for diagnosing spinal infections. Radiolabelled synthetic fragments of ubiquicidin, a naturally occurring human antimicrobial peptide that targets bacteria, have shown promise as infection specific radiopharmaceuticals. 2-[(18)F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET) with or without computed tomography (CT) is very useful in musculoskeletal infection. Sensitivities of more than 95% and specificities ranging from 75-99% have been reported in acute and subacute bone and soft-tissue infection. FDG is the radionuclide test of choice for spinal infection. It is sensitive, has a high negative predictive value, and can differentiate degenerative from infectious vertebral body end-plate abnormalities. Data on the accuracy of FDG for diagnosing diabetic pedal osteomyelitis and prosthetic joint infection are inconclusive and its role for these indications remains to be determined. Other PET radiopharmaceuticals that are under investigation as infection imaging agents include gallium-68 citrate ((68)Ga) and iodine-124 fialuridine ((124)I -FIAU). PMID- 26897337 TI - CT findings of adrenal schwannoma. AB - AIM: To analyse the computed tomography (CT) imaging features of patients with adrenal schwannoma. MATERIALS AND METHODS: Eight cases of adrenal schwannoma confirmed by histopathology were included in this study. All eight patients had undergone multiphase CT examinations. The features of the adrenal schwannoma in the CT images were analysed retrospectively in detail, including size, shape, margin, radiodensity, calcification, and enhancement pattern. RESULTS: There were six male and two female patients, with a median age of 44.5 years (range, 25-52 years). Two patients complained of right flank pain, and two with left upper abdominal discomfort, while the remaining patients were diagnosed by routine ultrasound examinations. On unenhanced CT images, all cases of adrenal schwannoma were well circumscribed, rounded or oval, heterogeneous masses with cystic components, with two cases exhibiting calcification, and three cases with septa. On enhanced CT images, all cases displayed mild heterogeneous enhancement of the tumour during the arterial phase, and progressive enhancement during the portal venous phase and equilibrium phase. CONCLUSION: Adrenal schwannoma commonly presents as a well-defined unilateral mass with cystic degeneration, septa, and a characteristic progressive contrast-enhancement pattern on multiphase enhanced scans. PMID- 26897338 TI - Molecular and immunological analysis of hen's egg yolk allergens with a focus on YGP42 (Gal d 6). AB - Allergy to hen's (Gallus domesticus) egg white is one of the most common forms of food allergy. Allergy to hen's yolk also exists however, to a lesser extent when compared to egg white allergy. Two minor allergens from the hen's egg yolk known as alpha-livetin (Gal d 5) and YGP42 (Gal d 6) were discovered recently. In this study, we investigated whether sensitization to egg white is associated with reactivity to egg yolk as well. Sera obtained from 25 patients with allergy to egg white were tested for specific IgE binding for egg yolk proteins through western immunoblotting. 36% of patients were found with true IgE-sensitization against egg yolk proteins. It was found that most of the IgE reactive yolk proteins were fragments of major precursor proteins of hen; vitellogenin-1 (VTG 1), vitellogenin-2 (VTG-2) and apolipoprotein B (Apo B). The egg yolk allergen Gal d 6 is the C-terminal part of VTG-1 and was found to be allergenic in significant percentage of egg white allergy patients. These results highlight the significance of Gal d 6 as an important allergen of egg yolk. Therefore, the secondary aim of this study involved developing a recombinant version of YGP42 in an Escherichia coli expression system. Recombinant Gal d 6 (rGal d6) was expressed as a fusion peptide with a 6 * His tag and purified using metal chelating resin. The inhibition ELISA results showed that rYGP42 was IgE reactive and was able to inhibit IgE binding to crude egg yolk (CEY) by up to 30%. Traditionally, it was thought that allergy to egg yolk occurred independently from sensitization to egg white. This study underlies the importance of concomitant sensitization to egg yolk proteins in patients allergic to egg white. Evidence reported in this study strongly suggests that egg yolk has potentially undiscovered allergens and therefore warrants further investigation. Furthermore, IgE reactive Gal d 6 presented in this study has the potential to be used in diagnosis and immunotherapy to treat egg allergy. PMID- 26897339 TI - C1 Inhibitor as a glycoprotein: The influence of polysaccharides on its function and autoantibody target. AB - C1 Inhibitor (C1Inh), a member of the Serine proteinase inhibitor family, is the most heavily glycosylated plasma protein. This work investigated the impact of C1Inh glycosylation on its function regarding protease targets and autoantibody binding. C1Inh deglycosylation was found to affect its function with O-linked polysaccharides, but not with N-linked polysaccharides, in controlling the contact phase but not C1s target, thus indicating the N-terminal domain's involvement in C1Inh function. Instructive samples demonstrated that O deglycosylation strongly suppressed autoantibody binding, suggesting the polysaccharide motif is an antibody target. The autoantibodies did not directly affect C1Inh function. PMID- 26897340 TI - Signaling via the CytoR/JAK/STAT/SOCS pathway: Emergence during evolution. AB - Cell-cell signaling represents an essential hallmark of multicellular organisms, which necessarily require a means of communicating between different cell populations, particularly immune cells. Cytokine receptor signaling through the Janus kinase/Signal Transducer and Activator of Transcription/Suppressor of Cytokine Signaling (CytoR/JAK/STAT/SOCS) pathway embodies one important paradigm by which this is achieved. This pathway has been extensively studied in vertebrates and protostomes and shown to play fundamental roles in development and function of immune and other cells. However, our understanding of the origins of the individual pathway components and their assembly into a functional pathway has remained limited. This study examined the origins of each component of this pathway through bioinformatics analysis of key extant species. This has revealed step-wise accretion of individual components over a large evolutionary time frame, but only in bilateria did a series of innovations allow their final coalescence to form a complete pathway. Assembly of the CytoR/JAK/STAT pathway has followed the retrograde model of pathway evolution, whereas addition of the SOCS component has adhered to the patchwork model. PMID- 26897341 TI - Models for gene duplication when dosage balance works as a transition state to subsequent neo-or sub-functionalization. AB - BACKGROUND: Dosage balance has been described as an important process for the retention of duplicate genes after whole genome duplication events. However, dosage balance is only a temporary mechanism for duplicate gene retention, as it ceases to function following the stochastic loss of interacting partners, as dosage balance itself is lost with this event. With the prolonged period of retention, on the other hand, there is the potential for the accumulation of substitutions which upon release from dosage balance constraints, can lead to either subsequent neo-functionalization or sub-functionalization. Mechanistic models developed to date for duplicate gene retention treat these processes independently, but do not describe dosage balance as a transition state to eventual functional change. RESULTS: Here a model for these processes (dosage plus neofunctionalization and dosage plus subfunctionalization) has been built within an existing framework. Because of the computational complexity of these models, a simpler modeling framework that captures the same information is also proposed. This model is integrated into a phylogenetic birth-death model, expanding the range of available models. CONCLUSIONS: Including further levels of biological reality in methods for gene tree/species tree reconciliation should not only increase the accuracy of estimates of the timing and evolutionary history of genes but can also offer insight into how genes and genomes evolve. These new models add to the tool box for characterizing mechanisms of duplicate gene retention probabilistically. PMID- 26897342 TI - Reducing Recreational Sedentary Screen Time: A Community Guide Systematic Review. AB - CONTEXT: Sedentary time spent with screen media is associated with obesity among children and adults. Obesity has potentially serious health consequences, such as heart disease and diabetes. This Community Guide systematic review examined the effectiveness and economic efficiency of behavioral interventions aimed at reducing recreational (i.e., neither school- nor work-related) sedentary screen time, as measured by screen time, physical activity, diet, and weight-related outcomes. EVIDENCE ACQUISITION: For this review, an earlier ("original") review (search period, 1966 through July 2007) was combined with updated evidence (search period, April 2007 through June 2013) to assess effectiveness of behavioral interventions aimed at reducing recreational sedentary screen time. Existing Community Guide systematic review methods were used. Analyses were conducted in 2013-2014. EVIDENCE SYNTHESIS: The review included 49 studies. Two types of behavioral interventions were evaluated that either (1) focus on reducing recreational sedentary screen time only (12 studies); or (2) focus equally on reducing recreational sedentary screen time and improving physical activity or diet (37 studies). Most studies targeted children aged <=13 years. Children's composite screen time (TV viewing plus other forms of recreational sedentary screen time) decreased 26.4 (interquartile interval= -74.4, -12.0) minutes/day and obesity prevalence decreased 2.3 (interquartile interval= -4.5, 1.2) percentage points versus a comparison group. Improvements in physical activity and diet were reported. Three study arms among adults found composite screen time decreased by 130.2 minutes/day. CONCLUSIONS: Among children, these interventions demonstrated reduced screen time, increased physical activity, and improved diet- and weight-related outcomes. More research is needed among adolescents and adults. PMID- 26897343 TI - Reducing Children's Recreational Sedentary Screen Time: Recommendation of the Community Preventive Services Task Force. PMID- 26897345 TI - From the Editor's Perspective.... PMID- 26897344 TI - The American College of Preventive Medicine Position Statement on Hepatitis C Virus Infection. AB - The American College of Preventive Medicine Prevention Practice Committee contributes to policy guidelines and recommendations on preventive health topics for clinicians and public health decision makers. After review of the currently available evidence, the College is providing a consensus-based set of recommendations designed to increase screening for and prevention of hepatitis C virus infection, increase linkage to care, improve access to treatment, and encourage development of hepatitis C virus-related quality measures. PMID- 26897346 TI - Global specialized stroke care delivery models. AB - Stroke services still vary enormously from country to country, with many countries providing no special services at all. The aim of this article is to provide a concise overview of the various types of acute stroke delivery systems at present available and critically describe merits and shortcomings. A systematic literature review was undertaken from 1990 to July 2014. Several models for stroke services have been developed mostly in the past 3 decades, mainly in the Western world. These include state-of-the-art stroke services ranging from highly specialized stroke centers to mobile stroke units for the community. In this light, the recommendations of the structure and organization of stroke units and stroke centers by the European Stroke Organization were recently published. What differentiates the various models of stroke care delivery across the globe is the diversity of services ranging from low key conventional care to highly sophisticated facilities with life saving interventional features via integrated stroke care infrastructure. Effective in hospital care for stroke should start in the emergency department where a swift and appropriate diagnosis should be made. The role of all brain neuroimaging procedures should have a defined a priori and proper demarcation between actions according to updated stroke care pathways and clinical protocols, which should be followed closely. These essential actions initiated by well-trained staff in the emergency department, should then be carried on in dedicated stroke facilities that is, a stroke unit. PMID- 26897348 TI - Use of noninvasive procedures in the cardiovascular risk assessment of hypertensive and normotensive individuals. AB - BACKGROUND: Arterial hypertension is associated with a high prevalence of vascular alterations. The use of noninvasive procedures to assess peripheral arterial diseases in the ranking of cardiovascular risks has been increasingly valued in clinical practice and should be adopted in nursing. OBJECTIVE: To identify the cardiovascular risk of hypertensive and normotensive individuals through the use of different noninvasive procedures to assess the vascular function and integrity: ankle-brachial index, pulse pressure, and delta brachial brachial and delta ankle-brachial indexes. METHODS: Quantitative, descriptive, and cross-sectional study undertaken at a health service in a Brazilian city. The research variables were age, sex, blood pressure, abdominal circumference, body mass index, ankle-brachial index, pulse pressure, and delta brachial-brachial and delta ankle-brachial indexes. RESULTS: Fifty-four (43.1%) normotensive and 69 (56.9%) hypertensive individuals participated in the study. Alterations were identified in ankle-brachial index, corresponding to mild and moderate arterial obstruction, among hypertensive individuals only (7.2%), with higher pulse pressure indices (P < 0.0001). The assessment of the correlation between the ankle-brachial index and pulse pressure showed no correlation in the normotensive group and a statistically significant correlation among hypertensive patients (Pearson's coefficient = -0.45, P < 0.0001, r(2) = 0.21). A statistically significant difference (P < 0.05) was found in the analysis of the mean delta brachial-brachial (6.2 +/- 0.71 mm Hg for normotensive and 10.16 +/- 1.45 mm Hg for hypertensive individuals) and delta ankle-brachial index (0.06 +/- 0.01 for normotensive and 0.11 +/- 0.01 for hypertensive individuals). CONCLUSIONS: The use of the proposed cardiovascular risk predictors shows more frequent alterations among hypertensive than normotensive individuals. PMID- 26897347 TI - Case report: Inadvertent intra-arterial injection during sclerotherapy may not be the disaster you think. AB - OBJECTIVES: Inadvertent intra-arterial injection is a rare and serious complication of sclerotherapy. Multiple treatments have been used in reported cases, with varying levels of success. We report a rare case of intra-arterial injection being treated with steroids and pulsed dye laser therapy and present a plan for future incidences. METHOD/CASE: A 52-year-old woman presented to the clinic looking for aesthetic improvement to telangiectatic veins on the anterior aspect of the right leg. She developed cutaneous necrosis after sclerotherapy injection with 4 mL of 0.5% liquid polidocanol. RESULTS: After 23 months of pulsed dye laser therapy and a course of oral prednisolone, the patient made a good recovery and is left with minimal lasting tissue damage. CONCLUSIONS: More research is needed into the area of treating cutaneous necrosis with a pulsed dye laser, but this case report indicates a possible future therapeutic use after a successful outcome. PMID- 26897350 TI - Acute Charcot foot and diabetes: A primer for the vascular nurse. AB - The clinical findings of the acute Charcot process includes a swollen, warm, and erythematous foot; although pain may be present, it is often mild and out of proportion to the clinical examination. The diagnosis is confirmed by radiologic imaging, and the diagnosis must be considered in any patient with diabetic neuropathy and unilateral foot swelling. Initial treatment calls for immediate immobilization of the foot. Failure to do so can lead to further foot damage, destruction, and possibly amputation. The patient with acute CN requires referral to a multidisciplinary team experienced in the care of the diabetic patient with this devastating condition. Patient education is a crucial component of the treatment plan when caring for a client with CN. PMID- 26897349 TI - Onychodystrophy: A possible marker for peripheral artery disease. AB - BACKGROUND: Peripheral artery disease (PAD) is quite common, particularly among the elderly. In advanced phases, it has an important impact in the quality of life, so it is recommended to identify this disease on early stages. Onychodystrophy is a deformity of the nail plate of any origin. Up to 50% are caused by fungal infection, the rest is mainly secondary to inflammatory processes. Nail inspection is a very accessible task, and valuation of PAD with the ankle-brachial index (ABI) is a noninvasive affordable technique. PATIENTS AND METHODS: One hundred two self-reported healthy participants were recruited, and the ABI was obtained, as well as inspection of the toenails in search of onychodystrophy. RESULTS AND CONCLUSIONS: Sixty-seven patients had abnormal ABI measurements. Of these, 39 were diagnosed as having onychodystrophy. These results are statistically significant to support the fact that onychodystrophy may be an early marker of asymptomatic PAD, allowing prompt intervention to ameliorate or stop disease progression. PMID- 26897351 TI - Review of article: Systematic review of compression following treatment for varicose veins by J. El-Sheikha, D. Carradice, S. Nandhra, et al (BJS 2015; 102: 719-725). PMID- 26897352 TI - Current status of ACL reconstruction in Germany. AB - INTRODUCTION: Reconstruction of the anterior cruciate ligament (ACL) is characterized by a variety of possibilities concerning its implementation. Different choices for grafts, fixation methods and tunnel positioning, as well as diverse technical tools are available and have clinical significance. Besides specific pre- and post-operative procedures, different indications for surgery and further surgeon-/clinic-related factors add variability to the treatment. In response to the lack of descriptive statistics about the implementation of these factors and the increasing numbers of ACL reconstructions this study has been conducted to display the current state of the treatment for ACL tears throughout Germany. MATERIALS AND METHODS: 709 clinics with surgical and orthopedic departments were provided an online-questionnaire that surveyed their statistical records (e.g. annually implemented operations, number of surgeons, duration of operations), implemented techniques (e.g. choice of grafts, construction of drilling tunnel, tibial/femoral fixation) and personal assessment (e.g. frequency/cause of graft failure, frequency/handling of infection). The response rate was 22 % (n = 155). Based on the statistical records a specialized group within the respondents was identified, enabling a cross-comparison between high- and low-volume surgeons. RESULTS: On average, the German orthopedic surgeons in the clinics surveyed annually performs 35 ACL reconstructions, with each operation lasting an average of 67 min. After subdividing the data with references to annually performed surgeries into high- and low-volume-surgeons, differences and common features between the subgroups become apparent. Differences between high- and low-volume-surgeons, respectively, show shorter duration of both ACL reconstructions (55 vs. 71 min) and revision ACL reconstructions (75 vs. 90 min), higher membership rates in professional associations (83 vs. 38 % have at least one membership), more frequent implementation of stability examinations (47 vs. 21 %) and different frequencies of femoral drilling techniques (using the anterolateral portal in 71 vs. 54 %). With reference to evaluating operation dates, choosing grafts and assessing reasons for graft failure both groups share commonalities, as well as regarding the predominant use of monofixation for femoral fixation (88 % of the participants-mainly with endobutton in 38 % and transfixation pin in 27 %) and for tibial fixation (81 % of the participants-mainly with bioabsorbable screw in 60 %). CONCLUSIONS: The treatment of ACL tears in the group of German clinics studied is characterized by a variety of surgical possibilities. This condition might reflect the entirety of clinics reconstructing ACL in Germany. For the first time, a descriptive statistical survey was implemented to display this variety and to provide insight into the current status quo. Within the entirety of surgeons implementing ACL reconstruction a specialized subgroup with a particular expertise seems to exist. PMID- 26897353 TI - Le modele stochastique SIS pour une epidemie dans un environnement aleatoire. AB - The stochastic SIS epidemic model in a random environment. In a random environment that is a two-state continuous-time Markov chain, the mean time to extinction of the stochastic SIS epidemic model grows in the supercritical case exponentially with respect to the population size if the two states are favorable, and like a power law if one state is favorable while the other is unfavorable. PMID- 26897354 TI - Asymptotic dynamics of some t-periodic one-dimensional model with application to prostate cancer immunotherapy. AB - In the case of some specific cancers, immunotherapy is one of the possible treatments that can be considered. Our study is based on a mathematical model of patient-specific immunotherapy proposed in Kronik et al. (PLoS One 5(12):e15,482, 2010). This model was validated for clinical trials presented in Michael et al. (Clin Cancer Res 11(12):4469-4478, 2005). It consists of seven ordinary differential equations and its asymptotic dynamics can be described by some t periodic one-dimensional dynamical system. In this paper we propose a generalised version of this t-periodic system and study the dynamics of the proposed model. We show that there are three possible types of the model behaviour: the solution either converges to zero, or diverges to infinity, or it is periodic. Moreover, the periodic solution is unique, and it divides the phase space into two sub regions. The general results are applied to the PC specific case, which allow to derive conditions guaranteeing successful as well as unsuccessful treatment. The results indicate that a single vaccination is not sufficient to cure the cancer. PMID- 26897355 TI - Nonlinear estimation of BOLD signals with the aid of cerebral blood volume imaging. AB - BACKGROUND: The hemodynamic balloon model describes the change in coupling from underlying neural activity to observed blood oxygen level dependent (BOLD) response. It plays an increasing important role in brain research using magnetic resonance imaging (MRI) techniques. However, changes in the BOLD signal are sensitive to the resting blood volume fraction (i.e., [Formula: see text]) associated with the regional vasculature. In previous studies the value was arbitrarily set to a physiologically plausible value to circumvent the ill posedness of the inverse problem. These approaches fail to explore actual [Formula: see text] value and could yield inaccurate model estimation. METHODS: The present study represents the first empiric attempt to derive the actual [Formula: see text] from data obtained using cerebral blood volume imaging, with the aim of augmenting the existing estimation schemes. Bimanual finger tapping experiments were performed to determine how [Formula: see text] influences the model estimation of BOLD signals within a single-region and multiple-regions (i.e., dynamic causal modeling). In order to show the significance of applying the true [Formula: see text], we have presented the different results obtained when using the real [Formula: see text] and assumed [Formula: see text] in terms of single-region model estimation and dynamic causal modeling. RESULTS: The results show that [Formula: see text] significantly influences the estimation results within a single-region and multiple-regions. Using the actual [Formula: see text] might yield more realistic and physiologically meaningful model estimation results. CONCLUSION: Incorporating regional venous information in the analysis of the hemodynamic model can provide more reliable and accurate parameter estimations and model predictions, and improve the inference about brain connectivity based on fMRI data. PMID- 26897356 TI - Multiplexed Engineering in Biology. AB - Biotechnology is the manufacturing technology of the future. However, engineering biology is complex, and many possible genetic designs must be evaluated to find cells that produce high levels of a desired drug or chemical. Recent advances have enabled the design and construction of billions of genetic variants per day, but evaluation capacity remains limited to thousands of variants per day. Here we evaluate biological engineering through the lens of the design-build-test cycle framework and highlight the role that multiplexing has had in transforming the design and build steps. We describe a multiplexed solution to the 'test' step that is enabled by new research. Achieving a multiplexed test step will permit a fully multiplexed engineering cycle and boost the throughput of biobased product development by up to a millionfold. PMID- 26897357 TI - Tumor Suppressor Candidate 1 Suppresses Cell Growth and Predicts Better Survival in Glioblastoma. AB - Glioblastoma (GBM) is the most common malignant brain tumor with poor prognosis and limited treatment options. Tumor suppressor candidate 1 (TUSC1) was recently identified as a potential tumor suppressor in human cancers. However, the expression and potential function of TUSC1 in GBM remain unclear. Herein, we report that TUSC1 is significantly decreased in GBM tissues and cell lines. Patients with high levels of TUSC1 displayed a significant better survival compared with those with low levels of TUSC1. Functional experiments demonstrated that exogenous expression of TUSC1 inhibited GBM cell proliferation and induced G1 phase arrest by down-regulating CDK4. Moreover, overexpression of TUSC1 retarded tumor growth in vivo. Together, our findings revealed that TUSC1 might be a crucial tumor suppressor gene and a novel therapeutic target for GBM. PMID- 26897358 TI - A novel anti-p21Ras scFv antibody reacting specifically with human tumour cell lines and primary tumour tissues. AB - BACKGROUND: The ras genes play an important role in the development and progression of human tumours. Neutralizing Ras proteins in the cytoplasm could be an effective approach to blocking ras signalling. In this study, we prepared anti p21Ras single chain fragment variable antibody (scFv) and investigated its immunoreactivity with human tumours. METHODS: The coding sequences of H-ras, K ras, and N-ras were separately ligated into the vector pET-28a(+). Then, recombinant expressing plasmids were induced by IPTG for p21Ras expression in E. coli. Hybridoma cell lines producing anti-p21Ras monoclonal antibodies were isolated using wildtype p21Ras proteins as immunogens. Anti-p21Ras scFv antibody was prepared from the hybridoma by the phage scFv display method. The immunoreactivity of the anti-p21Ras monoclonal antibody and the scFv antibody was identified by ELISA and immunocytochemistry. RESULTS: We prokaryotically expressed wildtype H-p21Ras, K-p21Ras and N-p21Ras and generated the hybridoma cell line KGH-R1, producing anti-p21Ras monoclonal antibodies. It was demonstrated that KGH-R1 monoclonal antibody could recognize wildtype and mutated H-p21Ras, K-p21Ras and N-p21Ras in human tumour cell lines. In all 14 types of primary human cancer tissues tested, the monoclonal antibody presented strong immunoreactivity but showed weak or negative immunoreactivity in the corresponding normal tissues. Subsequently, we prepared anti-p21Ras scFv from hybridoma KGH-R1, which showed the same immunoreactivity as the original monoclonal antibody. Sequence analysis demonstrated that the nucleotides and amino acids of the scFv exhibited an approximately 50 % difference from the anti p21Ras scFv reported previously. CONCLUSIONS: This study presents a novel anti p21Ras scFv antibody. Our data suggest that the scFv may be useful for ras signalling blockage and may be a potential therapeutic antibody for ras-derived tumours. PMID- 26897359 TI - Epigenetic regulation of the DRD4 gene and dimensions of attention deficit/hyperactivity disorder in children. AB - Recent evidence suggests that epigenetic regulation of the DRD4 gene may characterise specific aspects of ADHD symptomology. We tested associations between ADHD symptoms and epigenetic changes to the DRD4 gene in DNA extracted from blood and saliva in N = 330 children referred for a variety of behavioural and emotional problems. ADHD was indexed using DSM diagnoses as well as mother, father, and teacher reports. Methylation levels were assayed for the island of 18 CpG sites in the DRD4 receptor gene. A nearby SNP, rs3758653, was also genotyped as it has previously been shown to influence methylation levels. There was high consistency of methylation levels across CpG sites and tissue sources, and higher methylation levels were associated with the major allele of SNP rs3758653. Higher methylation levels were associated with more severe ADHD independent of SNP status, tissue source, ethnicity, environmental adversity, and comorbid conduct problems. The association applied specifically to the cognitive/attentional, rather than hyperactivity problems that characterise ADHD. The results indicate that epigenetic regulation of the DRD4 gene in the form of increased methylation is associated with the cognitive/attentional deficits in ADHD. PMID- 26897360 TI - A Boy with Relentless Pruritus: Job's Syndrome. AB - BACKGROUND: Job's syndrome (hyper IgE syndrome) is a very rare primary immunodeficiency disease that has an annual approximate incidence of less than 1/1,000,000. This manuscript aims to provide education regarding diagnosis and management strategies of this syndrome worldwide. CASE REPORT: A 6-year-old boy was seen at the clinic secondary to persistent pruritus interfering with sleep. At the age of 2 months, the patient developed diffuse eczematous and desquamating skin lesions. He was subsequently diagnosed with atopic dermatitis and managed conservatively. From 2 months to 7 years of age, intermittent exacerbations of dermatitis persisted despite an aggressive treatment regimen. The serum IgE level increased exponentially over a period of 7 years, with a peak value of 57,400 IU/ml. Molecular genetic testing revealed a dominant negative mutation within the SH2 domain of the Signal Transducer and Activator of Transcription (STAT3) gene. The patient was subsequently diagnosed with Job's syndrome. Management included proper skin care, prophylactic antibiotics, immunomodulating agents, and psychotherapy. CONCLUSIONS: Job's syndrome can often go unrecognized and masquerade as atopic dermatitis. Therefore, genetic testing for this condition should be obtained in all patients with treatment-refractory AD. Additionally, psychotherapy can be a successful management strategy for the grating psychological impact that can be imposed on children with excessive pruritus. PMID- 26897361 TI - Tolerance to stress differs between Asian green mussels Perna viridis from the impacted Jakarta Bay and from natural habitats along the coast of West Java. AB - It is an open question whether adverse habitat conditions, characteristic for many anthropogenically impacted coastal habitats, can determine resistance to abiotic stress in populations of residing invertebrates. We tested experimentally for differences in stress tolerance between individuals of the Asian green mussel Perna viridis stemming from the heavily impacted Jakarta Bay and from two natural sites, Lada Bay and Pelabuhan Ratu, West Java. Mussel performance under hyposalinity and hypoxia was assessed in laboratory assays by measuring fitness related response variables, e.g. body condition index, relative shell weight, byssus production, respiration rates and survival. We found stress-specific and population-specific differences in mussel resistance to adverse conditions: Individuals from the impacted Jakarta Bay performed better under hypoxia than their conspecifics from the natural sites, whereas the latter were more resistant to hyposalinity. We explain these differences by differential acclimation to environmental conditions in the respective habitats and by diverging degrees of food supply. PMID- 26897362 TI - Metals and pesticides in commercial bivalve mollusc production areas in the North and South Bays, Santa Catarina (Brazil). AB - Concentrations of heavy metals were quantified in mussels Perna perna and Pacific oysters Crassostrea gigas in 28 cultivation sites in the North and South Bays, SC (Brazil). Concentrations of pesticides were also quantified in these bivalve, water and sediment samples collected in 14 cultivation sites on four occasions in the period October 2012-October 2013. Pesticides were not detected in any of the mussel, oyster, water or sediment samples. The South Bay was found to be generally more contaminated with As while the North Bay showed higher concentrations of Ni. Concentrations of Pb and Cd were below the limit of detection of the method (0.5mg/kg) in all samples. Mussels accumulated more As and Ni than oysters, while the opposite was observed for Cu. Metal concentrations were below the maximum levels for foodstuffs specified in the Brazilian legislation. PMID- 26897363 TI - The TLR2/6 ligand PAM2CSK4 is a Th2 polarizing adjuvant in Leishmania major and Brugia malayi murine vaccine models. AB - BACKGROUND: Toll-like receptors (TLRs) play an important role in the innate and adaptive immune responses to pathogens, and are the target of new vaccine adjuvants. TLR2 plays a role in parasite recognition and activation of immune responses during cutaneous leishmaniasis infection, suggesting that TLR2 could be targeted by adjuvants for use in Leishmania vaccines. We therefore explored using Pam2CSK4 (Pam2) and Pam3CSK4 (Pam3) lipopeptide adjuvants, which activate TLR2/6 and TLR2/1 heterodimers respectively, in vaccine models for parasitic infections. METHODS: The use of lipopeptide adjuvants was explored using two vaccine models. For cutaneous leishmaniasis, the lipopeptide adjuvants Pam2 and Pam3 were compared to that of the Th1-driving double-stranded DNA TLR9 agonist CpG for their ability to improve the efficacy of the autoclaved Leishmania major (ALM) vaccine to protect against L. major infection. The ability of Pam2 to enhance the efficacy of a soluble Brugia malayi microfilariae extract (BmMfE) vaccine to protect against filarial infection was also assessed in a peritoneal infection model of B. malayi filariasis. Parasite antigen-specific cellular and humoral immune responses were assessed post-challenge. RESULTS: The use of lipopeptides in ALM-containing vaccines did not provide any protection upon infection with L. major, and Pam2 exacerbated the disease severity in vaccinated mice post challenge. Pam2, and to a lesser extent Pam3, were able to elevate antigen specific immune responses post-challenge in this model, but these responses displayed a skewed Th2 phenotype as characterised by elevated levels of IgG1. In the B. malayi vaccine model, the use of Pam2 as an adjuvant with BmMfE induced significant protective immunity to the same level as inclusion of an Alum adjuvant. Here, both Pam2 and Alum were found to enhance antigen-specific antibody production post-challenge, and Pam2 significantly elevated levels of antigen-specific IL-4, IL-5 and IL-13 produced by splenocytes. CONCLUSIONS: These data indicate that TLR2/6-targeting ligands could be considered as adjuvants for vaccines that require robust Th2 and/or antibody-dependent immunity. PMID- 26897364 TI - The preventive services use self-efficacy (PRESS) scale in older women: development and psychometric properties. AB - BACKGROUND: Preventive services offered to older Americans are currently under utilized despite considerable evidence regarding their health and economic benefits. Individuals with low self-efficacy in accessing these services need to be identified and provided self-efficacy enhancing interventions. Scales measuring self-efficacy in the management of chronic diseases exist, but do not cover the broad spectrum of preventive services and behaviors that can improve the health of older adults, particularly older women who are vulnerable to poorer health and lesser utilization of preventive services. This study aimed to evaluate the psychometric properties of a new preventive services use self efficacy scale, by measuring its internal consistency reliability, assessing internal construct validity by exploring factor structure, and examining differences in self-efficacy scores according to participant characteristics. METHODS: The Preventive Services Use Self-Efficacy (PRESS) Scale was developed by an expert panel at the University of Pittsburgh Center for Aging and Population Health - Prevention Research Center. It was administered to 242 women participating in an ongoing trial and the data were analyzed to assess its psychometric properties. An exploratory factor analysis with a principal axis factoring approach and orthogonal varimax rotation was used to explore the underlying structure of the items in the scale. The internal consistency of the subscales was assessed using Cronbach's alpha coefficient. RESULTS: The exploratory factor analysis defined five self-efficacy factors (self-efficacy for exercise, communication with physicians, self-management of chronic disease, obtaining screening tests, and getting vaccinations regularly) formed by 16 items from the scale. The internal consistency of the subscales ranged from .81 to .94. Participants who accessed a preventive service had higher self-efficacy scores in the corresponding sub-scale than those who did not. CONCLUSIONS: The 16-item PRESS scale demonstrates preliminary validity and reliability in measuring self efficacy in the use of preventive services among older women. It can potentially be used to evaluate the impact of interventions designed to improve self-efficacy in the use of preventive services in community-dwelling older women. PMID- 26897368 TI - Development and future directions of antiangiogenic therapy in hepatocellular carcinoma. PMID- 26897367 TI - Systematic reviews in paediatric multiple sclerosis and Creutzfeldt-Jakob disease exemplify shortcomings in methods used to evaluate therapies in rare conditions. AB - BACKGROUND: Randomized controlled trials (RCTs) are the gold standard design of clinical research to assess interventions. However, RCTs cannot always be applied for practical or ethical reasons. To investigate the current practices in rare diseases, we review evaluations of therapeutic interventions in paediatric multiple sclerosis (MS) and Creutzfeldt-Jakob disease (CJD). In particular, we shed light on the endpoints used, the study designs implemented and the statistical methodologies applied. METHODS: We conducted literature searches to identify relevant primary studies. Data on study design, objectives, endpoints, patient characteristics, randomization and masking, type of intervention, control, withdrawals and statistical methodology were extracted from the selected studies. The risk of bias and the quality of the studies were assessed. RESULTS: Twelve (seven) primary studies on paediatric MS (CJD) were included in the qualitative synthesis. No double-blind, randomized placebo-controlled trial for evaluating interventions in paediatric MS has been published yet. Evidence from one open-label RCT is available. The observational studies are before-after studies or controlled studies. Three of the seven selected studies on CJD are RCTs, of which two received the maximum mark on the Oxford Quality Scale. Four trials are controlled observational studies. CONCLUSIONS: Evidence from double blind RCTs on the efficacy of treatments appears to be variable between rare diseases. With regard to paediatric conditions it remains to be seen what impact regulators will have through e.g., paediatric investigation plans. Overall, there is space for improvement by using innovative trial designs and data analysis techniques. PMID- 26897366 TI - Low potency toxins reveal dense interaction networks in metabolism. AB - BACKGROUND: The chemicals of metabolism are constructed of a small set of atoms and bonds. This may be because chemical structures outside the chemical space in which life operates are incompatible with biochemistry, or because mechanisms to make or utilize such excluded structures has not evolved. In this paper I address the extent to which biochemistry is restricted to a small fraction of the chemical space of possible chemicals, a restricted subset that I call Biochemical Space. I explore evidence that this restriction is at least in part due to selection again specific structures, and suggest a mechanism by which this occurs. RESULTS: Chemicals that contain structures that our outside Biochemical Space (UnBiological groups) are more likely to be toxic to a wide range of organisms, even though they have no specifically toxic groups and no obvious mechanism of toxicity. This correlation of UnBiological with toxicity is stronger for low potency (millimolar) toxins. I relate this to the observation that most chemicals interact with many biological structures at low millimolar toxicity. I hypothesise that life has to select its components not only to have a specific set of functions but also to avoid interactions with all the other components of life that might degrade their function. CONCLUSIONS: The chemistry of life has to form a dense, self-consistent network of chemical structures, and cannot easily be arbitrarily extended. The toxicity of arbitrary chemicals is a reflection of the disruption to that network occasioned by trying to insert a chemical into it without also selecting all the other components to tolerate that chemical. This suggests new ways to test for the toxicity of chemicals, and that engineering organisms to make high concentrations of materials such as chemical precursors or fuels may require more substantial engineering than just of the synthetic pathways involved. PMID- 26897365 TI - On cognitive ecology and the environmental factors that promote Alzheimer disease: lessons from Octodon degus (Rodentia: Octodontidae). AB - Cognitive ecologist posits that the more efficiently an animal uses information from the biotic and abiotic environment, the more adaptive are its cognitive abilities. Nevertheless, this approach does not test for natural neurodegenerative processes under field or experimental conditions, which may recover animals information processing and decision making and may explain, mechanistically, maladaptive behaviors. Here, we call for integrative approaches to explain the relationship between ultimate and proximate mechanisms behind social behavior. We highlight the importance of using the endemic caviomorph rodent Octodon degus as a valuable natural model for mechanistic studies of social behavior and to explain how physical environments can shape social experiences that might influence impaired cognitive abilities and the onset and progression of neurodegenerative disorders such as Alzheimer disease. We consequently suggest neuroecological approaches to examine how key elements of the environment may affect neural and cognitive mechanisms associated with learning, memory processes and brain structures involved in social behavior. We propose the following three core objectives of a program comprising interdisciplinary research in O. degus, namely: (1) to determine whether diet types provided after weaning can lead to cognitive impairment associated with spatial memory, learning and predisposing to develop Alzheimer disease in younger ages; (2) to examine if early life social experience has long term effects on behavior and cognitive responses and risk for development Alzheimer disease in later life and (3) To determine if an increase of social interactions in adult degu reared in different degree of social stressful conditions alter their behavior and cognitive responses. PMID- 26897369 TI - Nobiletin: A Citrus Isolate to Make Sepsis Less Sour. PMID- 26897370 TI - Organization of DNA in a bacterial nucleoid. AB - BACKGROUND: It is unclear how DNA is packaged in a bacterial cell in the absence of nucleosomes. To investigate the initial level of DNA condensation in bacterial nucleoid we used in vivo DNA digestion coupled with high-throughput sequencing of the digestion-resistant fragments. To this end, we transformed E. coli cells with a plasmid expressing micrococcal nuclease. The nuclease expression was under the control of AraC repressor, which enabled us to perform an inducible digestion of bacterial nucleoid inside a living cell. RESULTS: Analysis of the genomic localization of the digestion-resistant fragments revealed their non-random distribution. The patterns observed in the distribution of the sequenced fragments indicate the presence of short DNA segments protected from the enzyme digestion, possibly because of interaction with DNA-binding proteins. The average length of such digestion-resistant segments is about 50 bp and the characteristic repeat in their distribution is about 90 bp. The gene starts are depleted of the digestion-resistant fragments, suggesting that these genomic regions are more exposed than genomic sequences on average. Sequence analysis of the digestion resistant segments showed that while the GC-content of such sequences is close to the genome-wide value, they are depleted of A-tracts as compared to the bulk genomic DNA or to the randomized sequence of the same nucleotide composition. CONCLUSIONS: Our results suggest that DNA is packaged in the bacterial nucleoid in a non-random way that facilitates interaction of the DNA binding factors with regulatory regions of the genome. PMID- 26897371 TI - Variability in Treatment of Post-coarctectomy Hypertension: A Multicenter Study. AB - Many pharmacologic therapies are available for treatment of post-coarctectomy hypertension in pediatric patients, which may lead to variability in care. Evaluation of trends in pharmacotherapy is necessary to evaluate quality of care. The Pediatric Health Information System database was queried from 2004 to 2013 for patients >30 days of age who had an ICD-9 code for coarctation of the aorta repair of coarctation by end-to-end anastomosis and had a RACHS-1 score of 2. Patients were excluded if they were admitted for >30 days, underwent mechanical circulatory support, or expired during the admission. Patient demographic and hospital data were collected along with antihypertensive pharmacotherapy. Trends in antihypertensive, analgesic, and sedative pharmacotherapy were evaluated, and multivariable statistical analysis was used to determine variables that significantly influenced cost. A total of 1636 patients [66.6 % male, median age 1.5 years (IQR 0.31-5.3)] met study criteria. Patients received a median of 3 (IQR 2-4) antihypertensive medications for a median of 8 days (IQR 5-11). Intravenous antihypertensive therapy was prescribed for a median 3 days (IQR 2-5) and oral therapy for a median of 1 day (IQR 1-2). Antihypertensive therapy was continued at discharge in 79.8 % of patients. Hospital cost increased by 36 % over the study period (p < 0.01), and nicardipine, dexmedetomidine, and intravenous acetaminophen were most strongly associated with increased cost (p < 0.001). Variability in the pharmacotherapy of post-coarctectomy hypertension in pediatric patients exists, and the use of newer agents may be influencing the cost of care. PMID- 26897373 TI - Mapping of enkephalins and adrenocorticotropic hormone in the squirrel monkey brainstem. AB - An immunocytochemical technique has been used to study for the first time the distribution of fibers and cell bodies containing leucine-enkephalin (leu-enk), methionine-enkephalin (met-enk) or adrenocorticotropic hormone (ACTH) in the whole brainstem of the squirrel monkey Saimiri sciureus. Cell bodies containing leu-enk or met-enk were found in the superior colliculus and the formatio reticularis tegmenti mesencephali, respectively. No immunoreactive cell bodies containing ACTH were observed. Leu-enk-immunoreactive fibers were observed in 40 brainstem nuclei/tracts/regions, fibers containing met-enk were found in 38 brainstem nuclei/tracts/regions and fibers containing ACTH were found in 26 nuclei/tracts/regions. In the latter case, the density of immunoreactive fibers was always low. A high/moderate density of leu-enk- or met-enk-immunoreactive fibers were found in 18 and 16 brainstem nuclei/tracts/regions, respectively. The distribution of immunoreactive fibers containing leu-enk or met-enk was quite similar, with both leu-enk and met-enk observed in 82.5 % of the squirrel monkey brainstem nuclei/tracts/regions. This relationship is less marked for met-enk and ACTH (60.5 %) and even lower for leu-enk and ACTH (52.5 %). In 42.5 % of the nuclei/tracts/regions of the squirrel monkey brainstem (colliculus superior, substantia grisea centralis, nucleus interpeduncularis, nucleus tractus spinalis nervi trigemini, nucleus tractus solitarii, nucleus parabrachialis, formatio reticularis, substantia nigra), we observed fibers containing all three neuropeptides. The widespread distribution reported here suggests that enkephalins and ACTH can be involved in several physiological functions. The distribution of the immunoreactive fibers reported here is quite similar to that previously reported for enkephalins and ACTH in Macaca species and humans. PMID- 26897372 TI - Neuroprotective Effect of Nanodiamond in Alzheimer's Disease Rat Model: a Pivotal Role for Modulating NF-kappaB and STAT3 Signaling. AB - Current therapeutic approaches of Alzheimer's disease (AD) are symptomatic and of modest efficacy, and there is no available effective cure or prevention of AD; hence, the need arise to search for neuroprotective agents to combat AD. The current study aimed at investigating the neuroprotective effect of nanodiamond (ND), adamantine-based nanoparticles, in aluminum-induced cognitive impairment in rats, an experimental model of AD. AD was induced by aluminum chloride (17 mg/kg, p.o. for 6 weeks) and confirmed by Morris water maze and Y-maze behavioral tests. Biochemical and histological analyses of the hippocampus were also performed. Aluminum-treated rats showed behavioral, biochemical, and histological changes similar to those associated with AD. ND improved learning and memory and reversed histological alterations. At the molecular levels, ND mitigated the increase of hippocampal beta-amyloid (Abeta42) and beta-site amyloid precursor protein cleaving enzyme-1 (BACE1) together with down-regulation of phosphorylated tau protein. It also modulated the excitatory glutamate neurotransmitter level. Furthermore, ND boosted the brain-derived neurotrophic factor (BDNF) and mitochondrial transcription factor-A (TFAM), suppressed the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), and curbed oxidative stress by hampering of inducible nitric oxide synthase (iNOS). Moreover, ND augmented the hippocampal levels of phosphorylated signal transducer and activator of transcription-3 (p-STAT3) and B cell leukemia/lymphoma-2 (Bcl-2) anti-apoptotic protein while diminished nuclear factor-kappaB (NF-kappaB) and caspase-3 (casp-3) expression. These findings indicate the protective effect of ND against memory deficits and AD-like pathological aberrations probably via modulating NF-kB and STAT3 signaling, effects mediated likely by modulating N methyl-D-aspartate (NMDA) receptors. PMID- 26897374 TI - Effects of Pulsed Electric Field (PEF) Treatment on Enhancing Activity and Conformation of alpha-Amylase. AB - To explore an efficient, safe, and speedy application of pulsed electric field (PEF) technology for enzymatic modification, effects of PEF treatment on the enzymatic activity, property and kinetic parameters of alpha-amylase were investigated. Conformational transitions were also studied with the aid of circular dichroism (CD) and fluorescence spectra. The maximum enzymatic activity of alpha-amylase was obtained under 15 kV/cm electric field intensity and 100 mL/min flow velocity PEF treatment, in which the enzymatic activity increased by 22.13 +/- 1.14% compared with control. The activation effect could last for 18 h at 4 degrees C. PEF treatment could widen the range of optimum temperature for alpha-amylase, however, it barely exerted any effect on the optimum pH. On the other hand, alpha-amylase treated by PEF showed an increase of Vmax, t1/2 and DeltaG, whereas a decrease of Km and k were observed. Furthermore, it can be observed from fluorescence and CD spectra that PEF treatment had increased the number of amino acid residues, especially that of tryptophan, on alpha-amylase surface with enhanced alpha-helices by 34.76% and decreased random coil by 12.04% on alpha-amylase when compared with that of untreated. These changes in structure had positive effect on enhancing alpha-amylase activity and property. PMID- 26897375 TI - t-Flavanone Improves the Male Pattern of Hair Loss by Enhancing Hair-Anchoring Strength: A Randomized, Double-Blind, Placebo-Controlled Study. AB - INTRODUCTION: trans-3,4'-Dimethyl-3-hydroxyflavanone (t-flavanone) is a derivative of astilbin that actively stimulates hair growth. The aim of the present study was to identify the mechanisms of action of t-flavanone on hair growth. METHODS: A double-blind usage test was performed with healthy volunteers who had androgenic alopecia (AGA). The subjects were divided into three groups with equal average baldness. The members in each group applied a vasodilator containing hair lotion supplemented with either 0, 0.1, or 0.3% (wt) t-flavanone twice a day for 30 weeks. The efficacy of t-flavanone was evaluated based on the parietal global and microscopic images. At week 30, the anchoring strength of hair was measured by the average peak force required for plucking out a single hair in a non-bald area using a digital force gauge. Desmoglein expression in the cultured human hair follicle was analyzed by Western blotting. RESULTS: After 30 weeks, t-flavanone significantly improved AGA and enhanced the hair-anchoring strength in a hair diameter-independent manner. Culture of human hair follicles in vitro with t-flavanone resulted in the upregulation of desmoglein protein expression. CONCLUSIONS: The results of our in vivo and in vitro studies demonstrated that t-flavanone enhanced the cell-cell adhesions in hair follicles; thus, reinforcement of hair rooting may be a mechanism by which t-flavanone promotes hair growth. FUNDING: Kao Corp. PMID- 26897376 TI - Comparative analysis of housekeeping and tissue-selective genes in human based on network topologies and biological properties. AB - Housekeeping genes are genes that are turned on most of the time in almost every tissue to maintain cellular functions. Tissue-selective genes are predominantly expressed in one or a few biologically relevant tissue types. Benefitting from the massive gene expression microarray data obtained over the past decades, the properties of housekeeping and tissue-selective genes can now be investigated on a large-scale manner. In this study, we analyzed the topological properties of housekeeping and tissue-selective genes in the protein-protein interaction (PPI) network. Furthermore, we compared the biological properties and amino acid usage between these two gene groups. The results indicated that there were significant differences in topological properties between housekeeping and tissue-selective genes in the PPI network, and housekeeping genes had higher centrality properties and may play important roles in the complex biological network environment. We also found that there were significant differences in multiple biological properties and many amino acid compositions. The functional genes enrichment and subcellular localizations analysis was also performed to investigate the characterization of housekeeping and tissue-selective genes. The results indicated that the two gene groups showed significant different enrichment in drug targets, disease genes and toxin targets, and located in different subcellular localizations. At last, the discriminations between the properties of two gene groups were measured by the F-score, and expression stage had the most discriminative index in all properties. These findings may elucidate the biological mechanisms for understanding housekeeping and tissue-selective genes and may contribute to better annotate housekeeping and tissue-selective genes in other organisms. PMID- 26897377 TI - ACC oxidase and miRNA 159a, and their involvement in fresh fruit bunch yield (FFB) via sex ratio determination in oil palm. AB - Oil palm (Elaeis guineesis Jacq.) is the most productive oil-bearing crop, yielding more oil per area than any other oil-bearing crops. However, there are still efforts to improve oil palm yield, in order to serve consumer and manufacturer demand. Oil palm produces female and male inflorescences in an alternating cycle. So, high sex ratio (SR), the ratio of female inflorescences to the total inflorescences, is a favorable trait in term of increasing yields in oil palm. This study aims to understand the genetic control for SR related traits, such as fresh fruit bunch yield (FFB), by characterizing genes at FFB quantitative trait loci (QTLs) on linkage 10 (chromosome 6) and linkage 15 (chromosome 10). Published oil palm sequences at the FFB QTLs were used to develop gene-based and simple sequence repeat (SSR) markers. We used the multiple QTL analysis model (MQM) to characterize the relationship of new markers with the SR traits in the oil palm population. The RNA expression of the most linked QTL genes was also evaluated in various tissues of oil palm. We identified EgACCO1 (encoding aminocyclopropane carboxylate (ACC) oxidase) at chromosome 10 and EgmiR159a (microRNA 159a) at chromosome 6 to be the most linked QTL genes or determinants for FFB yield and/or female inflorescence number with a phenotype variance explained (PVE) from 10.4 to 15 % and suggest that these play the important roles in sex determination and differentiation in oil palm. The strongest expression of EgACCO1 and the predicted precursor of EgmiR159a was found in ovaries and, to a lesser extent, fruit development. In addition, highly normalized expression of EgmiR159a was found in female flowers. In summary, the QTL analysis and the RNA expression reveal that EgACCO1 and EgmiR159a are the potential genetic factors involved in female flower determination and hence would affect yield in oil palm. However, to clarify how these genetic factors regulate female flower determination, more investigation of their down regulation or target may be essential. Additionally, if more sex determination genes controlled by plant hormones are identified, it may possible to reveal a crosstalk of sex determination genes with hormones and environment factors. PMID- 26897378 TI - Successful expression of the Bordetella petrii nitrile hydratase activator P14K and the unnecessary role of Ser115. AB - BACKGROUND: The activator P14K is necessary for the activation of nitrile hydratase (NHase). However, it is hard to be expressed heterogeneously. Although an N-terminal strep tagged P14K could be successfully expressed from Pseudomonas putida, various strategies for the over-expression of P14K are needed to facilitate further application of NHase. RESULTS: P14K was successfully expressed through fusing a his tag (his-P14K), and was over-expressed through fusing a gst tag (gst-P14K) at its N-terminus in the NHase of Bordetella petrii DSM 12804. The stability of gst-P14K was demonstrated to be higher than that of the his-P14K. In addition, the Ser115 in the characteristic motif CXLC-Ser115-C of the active center of NHase was found to be unnecessary for NHase maturation. CONCLUSIONS: Our results are not only useful for the NHase activator expression and the understanding of the role of Ser115 during NHase activation, but also helpful for other proteins with difficulty in heterologous expression. PMID- 26897379 TI - Adaptive leadership curriculum for Indian paramedic trainees. AB - BACKGROUND: Paramedic trainees in developing countries face complex and chaotic clinical environments that demand effective leadership, communication, and teamwork. Providers must rely on non-technical skills (NTS) to manage bystanders and attendees, collaborate with other emergency professionals, and safely and appropriately treat patients. The authors designed a NTS curriculum for paramedic trainees focused on adaptive leadership, teamwork, and communication skills critical to the Indian prehospital environment. METHODS: Forty paramedic trainees in the first academic year of the 2-year Advanced Post-Graduate Degree in Emergency Care (EMT-paramedic equivalent) program at the GVK-Emergency Management and Research Institute campus in Hyderabad, India, participated in the 6-day leadership course. Trainees completed self-assessments and delivered two brief video-recorded presentations before and after completion of the curriculum. RESULTS: Independent blinded observers scored the pre- and post-intervention presentations delivered by 10 randomly selected paramedic trainees. The third party judges reported significant improvement in both confidence (25 %, p < 0.01) and body language of paramedic trainees (13 %, p < 0.04). Self-reported competency surveys indicated significant increases in leadership (2.6 vs. 4.6, p < 0.001, d = 1.8), public speaking (2.9 vs. 4.6, p < 0.001, d = 1.4), self reflection (2.7 vs. 4.6, p < 0.001, d = 1.6), and self-confidence (3.0 vs. 4.8, p < 0.001, d = 1.5). CONCLUSIONS: Participants in a 1-week leadership curriculum for prehospital providers demonstrated significant improvement in self-reported NTS commonly required of paramedics in the field. The authors recommend integrating focused NTS development curriculum into Indian paramedic education and further evaluation of the long term impacts of this adaptive leadership training. PMID- 26897380 TI - Fully automated on-line solid phase extraction coupled to liquid chromatography tandem mass spectrometry for the simultaneous analysis of alkylphenol polyethoxylates and their carboxylic and phenolic metabolites in wastewater samples. AB - Three different sorbents (i.e. endcapped octadecylsilane, octasilane and styrene N-vinylpiperidinone co-polymer) were investigated in order to develop an on-line solid phase extraction-liquid chromatographic tandem mass spectrometric method (on-line SPE-LC-MS/MS) for the simultaneous analysis of alkylphenols polyethoxylate (AP(n)EOs, n = 1-8) and corresponding monocarboxylate (AP1ECs) and phenolic (APs) metabolites. The endcapped octadecylsilane was selected due to its full compatibility with a chromatographic approach, which allowed the elution of positively and negatively ionisable compounds in two distinct retention time windows, using a water-acetonitrile-tetrahydrofuran ternary gradient and a pellicular pentafluorophenyl column. On this SPE sorbent, the composition of the loading/clean-up solution was then optimized in order to achieve the best recoveries of target analytes. Under the best experimental conditions, the total analysis time per sample was 25 min and method detection limits (MDLs) were in the sub-nanograms per litre to nanograms per litre range (0.0081-1.0 ng L(-1)) for AP(n)EOs with n = 2-8, AP1ECs and APs, whereas for AP1EOs, an MDL of about 50 ng L(-1) was found. Using the mass-labelled compound spiking technique, the method performance was tested on inlet and outlet wastewater samples from three activated sludge treatment plants managing domestic and industrial sewages of the urban areas and the textile district of Prato and Bisenzio valley (Tuscany, Italy); in most cases, apparent recovery percentages approximately in the ranges of 50-110% and 80-120% were found for inlet and outlet samples, respectively. The on-line SPE-LC-MS/MS analysis of wastewater samples highlighted the presence of target analytes at concentrations ranging from few nanograms per litre to thousands nanograms per litre, depending on the compound and matrix analysed. AP2ECs were also tentatively identified in outlet samples. PMID- 26897382 TI - Functional outcome of knee arthrodesis with a monorail external fixator. AB - Several methods for obtaining knee arthrodesis have been described in the literature and world; over, the commonest cause for arthrodesis is a failed arthroplasty. Less commonly, as in this series, post-infective or traumatic causes may also require a knee fusion wherein arthroplasty may not be indicated. We present salient advantages along with the radiological and functional outcome of twenty four patients treated with a single monorail external fixator. All patients went on develop fusion at an average of 5.4 months with an average limb length discrepancy of 3 cm (1.5-6 cm). Improvements in functional outcome as assessed by the lower extremity functional score (LEFS), and the SF-36 was significant (p = 0.000). Knee arthrodesis with a single monorail external fixator is a reasonable single-staged salvage option in patients wherein arthroplasty may not be the ideal choice. The outcome, though far from ideal, is definitely positive and predictable. PMID- 26897381 TI - Enantiodifferentiation of 1,2-propanediol in various wines as phenylboronate ester with multidimensional gas chromatography-mass spectrometry. AB - Native concentrations and enantiomeric distribution of 1,2-propanediol in various wines were studied in order to evaluate its merits as a potential marker for aroma adulteration in wine. Heart-cut multidimensional gas chromatography coupled to mass spectrometry was applied to analyze 1,2-propanediol after salting-out of the polar phase, derivatization with phenyl boronic acid, and extraction with cyclohexane. The enantiomeric separation of the derivative was achieved with heptakis-(6-O-tert. butyl dimethylsilyl-2,3-di-O-acetyl)-beta-cyclodextrin as the chiral selector. In all authentic wines studied, 1,2-propanediol showed a high enantiomeric ratio in favor of the (R)-enantiomer, proving its potential as a marker for the adulteration with flavor extracts based on industrial 1,2 propandiol as solvent. Usually, concentrations varied between 15 and 100 mg/L. Higher values (up to 170 mg/L) were found in wines made with high amounts of dry berries. However, despite the higher concentrations of 1,2-propanediol in such wines, no apparent influence on the enantiomeric distribution could be detected. Graphical Abstract Detection of fraudulent aromatization of wines by enantiodifferentiation of 1,2-propanediol as its phenylboronate ester. PMID- 26897384 TI - Efficacy of axillary exclusion on seroma formation after modified radical mastectomy. AB - BACKGROUND: Breast cancer represented 35.1% of total female cancer cases in Egypt. Seroma is one of the most serious and common complications of mastectomy and axillary dissection with incidence between 15 and 81%. Seroma formation delays wound healing and increases susceptibility to infection, skin flap necrosis, and persistent pain as well as prolonging convalescence. Therefore, several techniques have been investigated to minimize seroma formation with no consistent success. Axillary exclusion is a technique aimed to obliterate dead space after axillary clearance and minimize collection. METHODS: Sixty-four patients were prepared for modified radical mastectomy. Of those, the study group contains 32 patients and the control group contains 32 patients. Study group had axillary exclusion while the other had the conventional procedure; total drain outputs were recorded daily for all patients prior to drain removal. The drains were removed when the daily drainage was less than 30 ml. RESULTS: This study contains 64 patients, the study group contains 32 patients, and the control group contains 32 patients. Age, BMI (mean control=31.7 and study=30.2), and tumor size were of no significant differences to be more concise on the effect of axillary exclusion. The mean of day of drain removal in the control group was 17.8 day (15 19) with a mean of total drain output of 4525.6 ml (4430-3660 ml) while the mean in the study group of day of drain removal was 11.3 (10-13) with a mean of total drain output of 1476.2 ml (620-2200 ml), p<0.00. CONCLUSIONS: Axillary exclusion technique is a valuable procedure that significantly decreases seroma postmastectomy and axillary dissection. PMID- 26897383 TI - Revised GH and cortisol cut-points for the glucagon stimulation test in the evaluation of GH and hypothalamic-pituitary-adrenal axes in adults: results from a prospective randomized multicenter study. AB - CONTEXT: Recent studies suggest using lower GH cut-points for the glucagon stimulation test (GST) in diagnosing adult GH deficiency (GHD), especially in obese patients. There are limited data on evaluating GH and hypothalamic pituitary-adrenal (HPA) axes using weight-based dosing for the GST. OBJECTIVE: To define GH and cortisol cut-points to diagnose adult GHD and secondary adrenal insufficiency (SAI) using the GST, and to compare fixed-dose (FD: 1 or 1.5 mg in patients >90 kg) with weight-based dosing (WB: 0.03 mg/kg). Response to the insulin tolerance test (ITT) was considered the gold standard, using GH and cortisol cut-points of >=3 ng/ml and >=18 ug/dL, respectively. DESIGN: 28 Patients with hypothalamic-pituitary disease and 1-2 (n = 14) or >=3 (n = 14) pituitary hormone deficiencies, and 14 control subjects matched for age, sex, estrogen status and body mass index (BMI) underwent the ITT, FD- and WB-GST in random order. RESULTS: Age, sex ratio and BMI were comparable between the three groups. The best GH cut-point for diagnosis of GHD was 1.0 (92 % sensitivity, 100 % specificity) and 2.0 ng/mL (96 % sensitivity and 100 % specificity) for FD- and WB-GST, respectively. Age negatively correlated with peak GH during FD-GST (r = 0.32, P = 0.04), but not WB-GST. The best cortisol cut-point for diagnosis of SAI was 8.8 ug/dL (92 % sensitivity, 100 % specificity) and 11.2 ug/dL (92 % sensitivity and 100 % specificity) for FD-GST and WB-GST, respectively. Nausea was the most common side effect, and one patient had a seizure during the FD-GST. CONCLUSION: The GST correctly classified GHD using GH cut-points of 1 ng/ml for FD-GST and 2 ng/ml for WB-GST, hence using 3 ng/ml as the GH cut-point will misclassify some GH-sufficient adults. The GST may also be an acceptable alternative to the ITT for evaluating the HPA axis utilizing cortisol cut-points of 9 ug/dL for FD-GST and 11 ug/dL for WB-GST. PMID- 26897385 TI - Cutaneous anaplastic large-cell lymphoma (ALCL): A comparative clinical feature and survival outcome analysis of 52 cases according to primary tumor site. AB - BACKGROUND: Cutaneous anaplastic large-cell lymphoma (ALCL) is primary extranodal or secondary to nodal disease. OBJECTIVE: We sought to analyze clinical features and survival outcomes by primary tumor site in patients with cutaneous ALCL. METHODS: Clinical features, survival outcomes, and prognostic factors of 52 patients with primary or secondary cutaneous ALCL to primary nodal disease were retrospectively evaluated using medical records. RESULTS: Although skin lesion characteristics did not significantly differ between groups, the head and neck location was more common in primary cutaneous ALCL, whereas cutaneous lesion extent was greater in secondary cutaneous ALCL. Skin lesion extent in primary cutaneous ALCL was indicative of extracutaneous dissemination development and skin lesion relapse. Neither anaplastic lymphoma kinase expression nor clinical stage affected skin lesion characteristics in secondary cutaneous ALCL. Patients with primary rather than secondary cutaneous ALCL demonstrated better survival outcomes. The skin lesion extent and location on the leg were associated with the tendency toward a poorer prognosis in primary cutaneous ALCL. The secondary cutaneous ALCL prognosis was not influenced by skin lesion characteristics. LIMITATIONS: This was a retrospective study in a single institution. CONCLUSION: Survival outcomes and prognostic factors in cutaneous ALCL differed by primary tumor site. PMID- 26897386 TI - Guidelines of care for the management of acne vulgaris. AB - Acne is one of the most common disorders treated by dermatologists and other health care providers. While it most often affects adolescents, it is not uncommon in adults and can also be seen in children. This evidence-based guideline addresses important clinical questions that arise in its management. Issues from grading of acne to the topical and systemic management of the disease are reviewed. Suggestions on use are provided based on available evidence. PMID- 26897387 TI - Histopathologic characteristics of scleromyxedema: A study of a series of 34 cases. AB - BACKGROUND: Few histologic studies describe the histopathologic aspects of scleromyxedema. OBJECTIVE: We sought to describe the histopathologic and immunohistochemical features of scleromyxedema in a large series of patients. METHODS: We studied all the cases with scleromyxedema diagnosed between 2000 and 2014 at participating centers. Sections with hematoxylin-eosin and special stains were examined. Immunohistochemistry for CD3, CD4, CD8, CD20, CD68, and factor XIIIa was performed in 10 cases. RESULTS: A total of 44 skin biopsy specimens from 34 patients were reviewed. Two different histopathologic patterns were observed: the classic microscopic triad (dermal mucin deposition, fibroblast proliferation, fibrosis) was identified in 34 specimens, whereas an interstitial granuloma annulare-like pattern was found in 10 specimens. A superficial perivascular infiltrate with T lymphocytes was found in all specimens whereas an interstitial proliferation of CD68(+) epithelioid cells was identified in the 10 specimens with an interstitial granuloma annulare-like pattern. Elastic fibers were largely lost, explaining the redundant folds of the disease. LIMITATIONS: This was a retrospective study. CONCLUSIONS: Scleromyxedema shows 2 histopathologic patterns, including the classic type with the microscopic triad of mucin, fibroblast proliferation and fibrosis, and an interstitial granuloma annulare-like pattern. Recognition of these histologic presentations expands the spectrum of scleromyxedema and highlights the difficulty in diagnosing this disabling condition in the absence of a clinicopathological correlation. PMID- 26897388 TI - Using the American College of Rheumatology (ACR) and Systemic Lupus International Collaborating Clinics (SLICC) criteria to determine the diagnosis of systemic lupus erythematosus (SLE) in patients with subacute cutaneous lupus erythematosus (SCLE). AB - BACKGROUND: Approximately 50% of patients with subacute cutaneous lupus erythematosus (SCLE) meet criteria for systemic lupus erythematosus (SLE). The Systemic Lupus International Collaborating Clinics (SLICC) developed new SLE criteria to improve the American College of Rheumatology (ACR) criteria but the SLICC criteria have not been evaluated in patients with SCLE. OBJECTIVE: We sought to determine how patients with SCLE/SLE meet the ACR and SLICC criteria to compare the 2 sets of criteria. METHODS: This was a retrospective analysis of 107 patients with SCLE enrolled in a database at the University of Pennsylvania. RESULTS: Patients with SCLE/SLE were more likely than those with only SCLE to have oral ulcers, positive anti-double-stranded DNA antibodies, and positive antinuclear antibody test findings using both sets of criteria. Patients with SCLE/SLE were also more likely to have low complement using the SLICC criteria. There was a statistically insignificant increase in individuals meeting the SLICC criteria. LIMITATIONS: Not all patients received comprehensive laboratory testing. CONCLUSIONS: Most patients with SCLE who formally meet criteria for SLE do so based on the laboratory and mucocutaneous criteria. Neither the ACR nor SLICC criteria distinguish patients with SCLE and major internal disease from patients with SCLE without major internal disease. PMID- 26897389 TI - Effect of smoking status on the efficacy of the SMART regimen in high risk asthma. AB - BACKGROUND AND OBJECTIVE: The optimal management of people with asthma with a significant smoking history is uncertain. The aim of this study was to determine whether the efficacy/safety profile of single combination inhaled corticosteroid (ICS)/long acting beta-agonist (LABA) inhaler maintenance and reliever therapy is influenced by smoking status. METHODS: We undertook secondary analyses from an open-label 24-week randomized study of 303 high risk adult asthma patients randomized to budesonide/formoterol 200/6-ug-metred dose inhaler for maintenance (two actuations twice daily) and either budesonide/formoterol 200/6-ug-metred dose inhaler one actuation ('single ICS/LABA maintenance and reliever therapy (SMART)' regimen) or salbutamol 100 ug 1-2 actuations for symptom relief ('Standard' regimen). Smoking status was classified in to three groups, as 'current', 'ex' or 'never', and a smoking/treatment interaction term tested for each outcome variable. The primary outcome variable was number of participants with at least one severe exacerbation. RESULTS: There were 59 current, 97 ex and 147 never smokers included in the analyses. The smoking status/treatment interaction term was not statistically significant for any of the outcome measures. With adjustment for smoking status, the number of participants with severe exacerbations was lower with the SMART regimen (OR 0.45, 95% CI: 0.26 0.77, P = 0.004; P value for interaction between smoking status and treatment 0.29). CONCLUSION: We conclude that the favourable safety/efficacy profile of the SMART regimen applies to patients with high risk asthma, irrespective of smoking status. PMID- 26897390 TI - Costs associated with emergency care and hospitalization for severe hypoglycemia. AB - BACKGROUND AND AIMS: We aimed to determine the direct economic cost of the management of severe hypoglycemia among people with diabetes in Italy. METHODS AND RESULTS: Data of cases with an acceptance diagnosis of hypoglycemia between January 2011 and June 2012 were collected in 46 Emergency Departments (EDs). Emergency care costs were computed by estimating the average cost per ambulance service, ED visit and short-term (<24 h) observation period. Hospitalization expenditure was estimated using the average cost reimbursed by the Italian healthcare system for hospital admission per patient with diabetes in a specific hospital ward. We retrieved 3516 hypoglycemic episodes occurring in subjects with diabetes. Half the cases (51.8%) required referral to EDs by means of the emergency ambulance services. A total of 1751 cases (49.8%) received an ED visit followed by discharge; 604 cases (17.2%) received a short-term observation period; 1161 (33.1%) were hospitalized. Unit costs for emergency care management were estimated at ?205 for an ambulance call, ?23 for an ED visit, and ?220 for a short-term observation. The mean hospitalization cost was estimated at ?5317; the average cost per each severe hypoglycemic event totaled ?1911. From a base case assumption, the total direct cost of severe hypoglycemia in patients with diabetes in Italy was estimated to be approximately ?23 million per year. CONCLUSION: Severe hypoglycemia in patients with diabetes constitutes a remarkable economic burden for national healthcare systems. Measures for preventing hypoglycemia are mandatory in diabetes management programs considering the impact on patients and on health spending. PMID- 26897391 TI - Where does the time go? Patterns of physical activity in adolescent youth. AB - OBJECTIVES: To explore daily patterns of physical activity in early adolescent youth, and identify whether patterns differed across varying activity levels. DESIGN: Cross-sectional observational study. METHODS: Adolescent youth (n=715, 11.8-14.4 years) were asked to wear an Actigraph accelerometer for a 9-day period. Average daily and hourly minutes spent in moderate-vigorous physical activity (MVPA) were calculated for each participant. Participants were grouped into sex-specific quartiles (Q) based on average daily MVPA accumulation (Q4 most active, Q1 least active). Principal components analysis was used to identify, from hourly MVPA data, distinct time blocks for Weekday and Weekend days. Mixed between-within ANOVA's were conducted separately by gender to assess the impact of Quartile grouping on minutes of MVPA across the distinct time blocks. RESULTS: Males accumulated significantly more minutes of MVPA daily than females (55.3+/ 21.6min, versus 47.4+/-18.1min). Principal Components Analysis revealed three distinct time components for MVPA during weekdays, and weekend days. The total difference between Q4 and Q1 was greatest 'Weekend Afternoons' for Males (22min), and 'Weekend Midday' for females (12.8min); with Q4 accumulating significantly more MVPA in these time periods than the other three Quartiles (p<0.05). CONCLUSIONS: This study points to the weekend midday and afternoon periods as particular time blocks to target for intervening with inactive youth. Future research should examine the reasons why some youth choose to be active during these particular periods while others do not, with a view to developing appropriate strategies for intervention. PMID- 26897392 TI - 95% prevalence of abnormality on hip MRI in elite academy level rugby union: A clinical and imaging study of hip disorders. AB - OBJECTIVES: To identify the prevalence of hip disorders in elite level academy rugby union players using clinical and radiological investigation comparing findings to active controls. DESIGN: Cross-sectional, controlled study. METHODS: Participants were assessed clinically using validated questionnaire (HAGOS) and physical testing procedures. Active ROM of all hip movements were measured using a goniometer and hip-specific clinical tests including the FABER and the Thomas test examined functional hip motion. Physical tests were compared to age, gender and activity matched controls. The rugby-playing participants underwent dedicated non-arthrographic 3T MRI imaging of the hip in axial oblique, sagittal and coronal planes to assess anatomical abnormality. RESULTS: The rugby cohort had significantly reduced ROM of internal/external rotation, extension and FABER scores compared to the controls. Symptoms were reported by 65% of rugby players (HAGOS symptom score <89.3) versus 15% in controls. There was a 95% prevalence of abnormality on MRI (19 of 20 players); 80% of the elite rugby players had labral pathology, 55% had a cam deformity (45% left sided 30% right-sided) and 25% had either unilateral or bilateral chondral wear. CONCLUSIONS: The prevalence of abnormality on MRI of the hip is high in rugby players at 95% of study participants. The percentage reporting symptoms was lower at 65% of the cohort although this was significantly higher than (non-rugby) matched controls at 15% of participants. Rugby players demonstrated significantly reduced ROM of the hip compared to controls. Further prospective research is required to investigate the long term sequelae of these findings. PMID- 26897394 TI - Genome-wide association study of tick resistance in South African Nguni cattle. AB - Ticks and tick-borne diseases are among the main causes of economic loss in the South African cattle industry through high morbidity and mortality rates. Concerns of the general public regarding chemical residues may tarnish their perceptions of food safety and environmental health when the husbandry of cattle includes frequent use of acaricides to manage ticks. The primary objective of this study was to identify single nucleotide polymorphism (SNP) markers associated with host resistance to ticks in South African Nguni cattle. Tick count data were collected monthly from 586 Nguni cattle reared in four herds under natural grazing conditions over a period of two years. The counts were recorded for six species of ticks attached in eight anatomical locations on the animals and were summed by species and anatomical location. This gave rise to 63 measured phenotypes or traits, with results for 12 of these traits being reported here. Tick count (x) data were transformed using log10(x+1) and the resulting values were examined for normality. DNA was extracted from hair and blood samples and was genotyped using the Illumina BovineSNP50 assay. After quality control (call rate >90%, minor allele frequency >0.02), 40,436 SNPs were retained for analysis. Genetic parameters were estimated and association analysis for tick resistance was carried out using two approaches: a genome-wide association (GWA) analysis using the GenABEL package and a regional heritability mapping (RHM) analysis. The Bonferroni genome-wide (P<0.05) corrected significance threshold was 1.24*10(-6), with 2.47*10(-5) as the suggestive significance threshold (P<0.10) (i.e., one false positive per genome scan) in the GWA analysis. Likelihood ratio test (LRT) thresholds for genome-wide and suggestive significance were 13.5 and 9.15 for the RHM analysis. Six ixodid tick species were identified, with Amblyomma hebraeum (the vector for Heartwater disease) being the dominant species. Heritability estimates (h(2)) from the fitted animal and sire models ranged from 0.02+/-0.00 to 0.17+/-0.04 for the transformed tick count data. Several genomic regions harbouring quantitative trait loci (QTL) were identified for different tick count traits by both the GWA and RHM approaches. Three genome-wide significant regions on chromosomes 7, 10 and 19 were identified for total tick count on the head, total body A. hebraeum tick count and total A. hebraeum on the perineum region, respectively. Additional regions significant at the suggestive level were identified on chromosomes 1, 3, 6, 7, 8, 10, 11, 12, 14, 15, 17, 19 and 26 for several of the traits. The GWA approach identified more genomic regions than did the RHM approach. The chromosomal regions identified here as harbouring QTL underlying variation in tick burden form the basis for further analyses to identify specific candidate genes and polymorphisms related to cattle tick resistance and provide the potential for marker-assisted selection in Nguni cattle. PMID- 26897393 TI - BDNF-induced presynaptic facilitation of GABAergic transmission in the hippocampus of young adults is dependent of TrkB and adenosine A2A receptors. AB - Brain-derived neurotrophic factor (BDNF) and adenosine are widely recognized as neuromodulators of glutamatergic transmission in the adult brain. Most BDNF actions upon excitatory plasticity phenomena are under control of adenosine A2A receptors (A2ARs). Concerning gamma-aminobutyric acid (GABA)-mediated transmission, the available information refers to the control of GABA transporters. We now focused on the influence of BDNF and the interplay with adenosine on phasic GABAergic transmission. To assess this, we evaluated evoked and spontaneous synaptic currents recorded from CA1 pyramidal cells in acute hippocampal slices from adult rat brains (6 to 10 weeks old). BDNF (10-100 ng/mL) increased miniature inhibitory postsynaptic current (mIPSC) frequency, but not amplitude, as well as increased the amplitude of inhibitory postsynaptic currents (IPSCs) evoked by afferent stimulation. The facilitatory action of BDNF upon GABAergic transmission was lost in the presence of a Trk inhibitor (K252a, 200 nM), but not upon p75(NTR) blockade (anti-p75(NTR) IgG, 50 MUg/mL). Moreover, the facilitatory action of BDNF onto GABAergic transmission was also prevented upon A2AR antagonism (SCH 58261, 50 nM). We conclude that BDNF facilitates GABAergic signaling at the adult hippocampus via a presynaptic mechanism that depends on TrkB and adenosine A2AR activation. PMID- 26897395 TI - Molecular diagnosis of Rickettsia infection in patients from Tunisia. AB - Diagnosis of rickettsioses had largely benefited from the development of molecular techniques. Unfortunately, in Tunisia, despite the large number of rickettsial cases registered every year, the Rickettsia species remain unidentified. In this study, we aimed to detect the Rickettsia species in clinical samples using molecular tests. A study was established to analyze skin biopsies, cutaneous swabs, and cerebrospinal fluid samples taken from clinically suspected patients to have rickettsial infection. Two molecular techniques were used to detect Rickettsia DNA: quantitative real time PCR (qPCR) and reverse line blot test (RLB). An analysis of the RLB hybridization assay results revealed the presence of Rickettsia DNA in skin biopsies (40.6%) and swabs (46.7%). Rickettsia conorii was the most prevalent identified species among tested samples. Other species of interest include Rickettsia typhi and Rickettsia massiliae. Using qPCR positivity rates in skin biopsies was 63.7% against 80% in swabs. R. conorii was the most frequently detected species, followed by R. typhi. The agreement between the two techniques was 68.6% (kappa=0.33). Molecular tests, especially using specific probes qPCR, allow for a rapid, better and confident diagnosis in clinical practice. They improve the survey of Mediterranean spotted fever which is considered to be the most important rickettsial infection in humans in Tunisia. PMID- 26897396 TI - Mapping human risk of infection with Borrelia burgdorferi sensu lato, the agent of Lyme borreliosis, in a periurban forest in France. AB - Lyme borreliosis is a major zoonosis in Europe, with estimates of over 26,000 cases per year in France alone. The etiological agents are spirochete bacteria that belong to the Borrelia burgdorferi sensu lato (s. l.) complex and are transmitted by hard ticks among a large range of vertebrate hosts. In Europe, the tick Ixodes ricinus is the main vector. In the absence of a vaccine and given the current difficulties to diagnose and treat chronic Lyme syndromes, there is urgent need for prevention. In this context, accurate information on the spatial patterns of risk of exposure to ticks is of prime importance for public health. The objective of our study was to provide a snapshot map of the risk of human infection with B. burgdorferi s. l. pathogens in a periurban forest at a high resolution, and to analyze the factors that contribute to variation in this risk. Field monitoring took place over three weeks in May 2011 in the suburban Senart forest (3,200ha; southeast of Paris), which receives over 3 million people annually. We sampled ticks over the entire forest area (from 220 forest stands with a total area of 35,200m(2)) and quantified the density of questing nymphs (DON), the prevalence of infection among nymphs (NIP), and the density of infected nymphs (DIN), which is the most important predictor of the human risk of Lyme borreliosis. For each of these response variables, we explored the relative roles of weather (saturation deficit), hosts (abundance indices of ungulates and Tamias sibiricus, an introduced rodent species), vegetation and forest cover, superficial soil composition, and the distance to forest roads. In total, 19,546 questing nymphs were collected and the presence of B. burgdorferi s. l. was tested in 3,903 nymphs by qPCR. The mean DON was 5.6 nymphs per 10m(2) (standard deviation=10.4) with an average NIP of 10.1% (standard deviation=0.11). The highest DIN was 8.9 infected nymphs per 10m(2), with a mean of 0.59 (standard deviation=0.6). Our mapping and modeling revealed a strong heterogeneity of risk within the forest. The highest risk was found in the eastern part of the forest and localized patches in the northwestern part. Lyme borreliosis risk was positively associated with stands of deciduous trees (mainly oaks) and roe deer abundance. Contrary to expectations, DIN actually increased with distance from the point of introduction of T. sibiricus (i.e., DIN was higher in areas with potentially lower abundances of T. sibiricus). Thus, despite the fact that T. sibiricus is an important reservoir host for B. burgdorferi s. l., our study found that other explanatory factors played a more important role in determining the density of infected ticks. Precise mapping of the risk of exposure to Lyme borreliosis in a highly visited forest represents an important tool for targeting prevention and control measures, as well as making the general public and local health officials aware of the risks. PMID- 26897397 TI - The association between CYP19 polymorphism and endometriosis risk: a system review and meta-analysis. AB - OBJECTIVE: Endometriosis is a chronic, inflammatory, estrogen dependent disease. Genetic variation of estrogen biosynthesis and metabolic genes is associated with the risk of endometriosis. The CYP19 gene, encoding aromatase, plays an important role in the conversion of androgens to estrogens. Polymorphisms in the CYP19 gene are associated with circulating estrogen levels and estrogen/testosterone ratio. The aim of present study is to evaluate the impact of the CYP19 rs10046 polymorphism on endometriosis risk. METHODS: Embase, PubMed and other databases were searched for eligible case-control studies. A fixed-effects or random effects model was appropriately selected to calculate the pooled odds ratios (ORs). RESULTS: A total of 8 case-control studies including 993 cases and 1956 controls were available. Overall, the pooled results indicated that CYP19 rs10046 polymorphism was not associated with endometriosis risk (for heterozygous CC vs. CT carriers OR=1.00, 95% CI: 0.82-1.21; for homozygous CC vs. TT carriers OR=1.06, 95% CI: 0.83-1.35; allele contrast C vs. T OR=1.01, 95% CI: 0.90-1.14; dominant model CC vs. CT+TT OR=1.02, 95% CI: 0.85-1.23; recessive model CC+CT vs. TT OR=1.05, 95% CI: 0.85-1.30). Heterogeneity among studies was founded in dominant model and allele contrast. Galbraith plot analyses were performed to assess the source of heterogeneity and one study was found to be contributor of heterogeneity. The heterogeneity decreased significantly after excluding that study. CONCLUSION: Present meta-analysis reveals that CYP19 rs10046 polymorphism may be not correlated to endometriosis risk. PMID- 26897398 TI - The art of performing a safe forceps delivery: a skill to revitalise. AB - The number of forceps deliveries is globally falling possibly due to Obstetricians gaining more experience and competence in the use of Ventouse deliveries. The declining use of traction forceps can increase the rate of second stage caesarean sections, which may have a long-term impact on the overall rate of vaginal births, despite the efforts of improving uptake of vaginal births after caesarean sections. The failures in forceps deliveries are commonly related to inaccurate assessment of the foetal position and station, which can be addressed by gaining sound clinical experience and applying intra-partum scanning to determine the fetal head position in the second stage, and should be part of the core curriculum in obstetric training. The alternate techniques of rotation, like digital and manual rotation, should be taught and encouraged in cases where rotation is required, which will significantly increase the success rate of instrumental deliveries. PMID- 26897399 TI - Effect of hydrosalpinx on uterine and ovarian hemodynamics in women with tubal factor infertility. AB - OBJECTIVE: To evaluate the effect of hydrosalpinx on uterine and ovarian blood flows in women with tubal factor infertility. STUDY DESIGN: In a cross-sectional study at a university teaching hospital, 60 women with hydrosalpinx-related tubal infertility (hydrosalpinx group) were compared with 60 women with male or unexplained infertility (non-hydrosalpinx group). In the mid-luteal (peri implantation) phase of the cycle, endometrial thickness, uterine and ovarian artery pulsatility index (PI) and resistance index (RI), and endometrial and ovarian volume and 3D power Doppler vascularization index (VI), flow index (FI), and vascularization flow index (VFI) were measured in both groups. RESULTS: The endometrial VI (p=0.002), FI (p=0.041), and VFI (p=0.018), and ovarian VI (p=0.011), and VFI (p=0.015) were significantly lower in the hydrosalpinx group than in the non-hydrosalpinx group. However, the endometrial thickness, uterine artery PI and RI, ovarian artery PI and RI, endometrial volume, and ovarian volume and FI were not significantly different between the two groups. CONCLUSION: Hydrosalpinx is associated with impaired endometrial and ovarian blood flows which may adversely affect endometrial receptivity and oocyte quality. PMID- 26897400 TI - Rapid screening of flonicamid residues in environmental and agricultural samples by a sensitive enzyme immunoassay. AB - A fast and sensitive polyclonal antibody-based enzyme-linked immunosorbent assay (ELISA) was developed for the analysis of flonicamid in environmental and agricultural samples. Two haptens of flonicamid differing in spacer arm length were synthesized and conjugated to proteins to be used as immunogens for the production of polyclonal antibodies. To obtain most sensitive combination of antibody/coating antigen, two antibodies were separately screened by homologous and heterologous assays. After optimization, the flonicamid ELISA showed that the 50% inhibitory concentration (IC50 value) was 3.86mgL(-1), and the limit of detection (IC20 value) was 0.032mgL(-1). There was no cross-reactivity to similar tested compounds. The recoveries obtained after the addition of standard flonicamid to the samples, including water, soil, carrot, apple and tomato, ranged from 79.3% to 116.4%. Moreover, the results of the ELISA for the spiked samples were largely consistent with the gas chromatography (R(2)=0.9891). The data showed that the proposed ELISA is an alternative tool for rapid, sensitive and accurate monitoring of flonicamid in environmental and agricultural samples. PMID- 26897402 TI - Modeling dynamics of (137)Cs in forest surface environments: Application to a contaminated forest site near Fukushima and assessment of potential impacts of soil organic matter interactions. AB - A process-based model for (137)Cs transfer in forest surface environments was developed to assess the dynamic behavior of Fukushima-derived (137)Cs in a Japanese forest. The model simulation successfully reproduced the observed data from 3year migration of (137)Cs in the organic and mineral soil layers at a contaminated forest near Fukushima. The migration of (137)Cs from the organic layer to the mineral soil was explained by the direct deposition pattern on the forest floor and the turnover of litter materials in the organic layer under certain ecological conditions. Long-term predictions indicated that more than 90% of the deposited (137)Cs would remain within the top 5cm of the soil for up to 30years after the accident, suggesting that the forest acts as an effective long term reservoir of (137)Cs with limited transfer via the groundwater pathway. The model was also used to explore the potential impacts of soil organic matter (SOM) interactions on the mobility and bioavailability of (137)Cs in the soil-plant system. The simulation results for hypothetical organic soils with modified parameters of (137)Cs turnover revealed that the SOM-induced reduction of (137)Cs adsorption elevates the fraction of dissolved (137)Cs in the soil solution, thereby increasing the soil-to-plant transfer of (137)Cs without substantially altering the fractional distribution of (137)Cs in the soil. Slower fixation of (137)Cs on the flayed edge site of clay minerals and enhanced mobilization of the clay-fixed (137)Cs in organic-rich soils also appeared to elevate the soil-to plant transfer of (137)Cs by increasing the fraction of the soil-adsorbed (exchangeable) (137)Cs. A substantial proportion (approximate 30%-60%) of (137)Cs in these organic-rich soils was transferred to layers deeper than 5cm decades later. These results suggested that SOM influences the behavior of (137)Cs in forests over a prolonged period through alterations of adsorption and fixation in the soil. PMID- 26897401 TI - Characterization of the chemical composition of PM2.5 emitted from on-road China III and China IV diesel trucks in Beijing, China. AB - The composition of diesel exhaust fine particulate matter (PM2.5) is of growing interest because of its impacts on health and climatic factors and its application in source apportionment and aerosol modeling. We characterized the detailed chemical composition of the PM2.5, including the organic carbon (OC), elemental carbon (EC), water-soluble ions (WSIs), and elemental contents, emitted from China III and China IV diesel trucks (nine each) based on real-world measurements in Beijing using a portable emissions measurement system (PEMS). Carbonaceous compounds were the dominant components (totaling approximately 87%) of the PM2.5, similar to the results (greater than 80% of the PM2.5) of our previous study of on-road China III diesel trucks. In general, the amounts of individual component groups (carbonaceous compounds, WSIs, and elements) and PM2.5 emissions for China IV diesel trucks were lower than those of China III diesel trucks of the same size, except for the WSIs and elements for the light- and medium-duty diesel trucks. The EC/OC mass ratios were strongly dependent on the emission standards, and the ratios of China IV diesel trucks were higher than those of China III diesel trucks of the same size. The chemical species in the PM2.5 were significantly affected by the driving conditions. Overall, the emission factors (EFs) of the PM2.5 and OC under non-highway (NHW) driving conditions were higher than those under highway (HW) driving conditions, and the EC/OC mass ratios presented an increasing trend, with decreasing OC/PM2.5 and increasing EC/PM2.5 from NHW to HW driving conditions; similar trends were reported in our previous study. In addition, Pearson's correlation coefficients among the PM2.5 species were analyzed to determine the relationships among the various chemical components. PMID- 26897403 TI - Sources and transport of contaminants of emerging concern: A two-year study of occurrence and spatiotemporal variation in a mixed land use watershed. AB - The occurrence and spatiotemporal variation of 26 contaminants of emerging concern (CECs) were evaluated in 68 water samples in 2011-2012 in the Zumbro River watershed, Minnesota, U.S.A. Samples were collected across a range of seasonal/hydrological conditions from four stream sites that varied in associated land use and presence of an upstream wastewater treatment plant (WWTP). Selected CECs included human/veterinary pharmaceuticals, personal care products, pesticides, phytoestrogens, and commercial/industrial compounds. Detection frequencies and concentrations varied, with atrazine, metolachlor, acetaminophen, caffeine, DEET, and trimethoprim detected in more than 70% of samples, acetochlor, mecoprop, carbamazepine, and daidzein detected in 30%-50% of samples, and 4-nonylphenol, cotinine, sulfamethoxazole, erythromycin, tylosin, and carbaryl detected in 10%-30% of samples. The remaining target CECs were not detected in water samples. Three land use-associated trends were observed for the detected CECs. Carbamazepine, 4-nonylphenol, erythromycin, sulfamethoxazole, tylosin, and carbaryl profiles were WWTP-dominated, as demonstrated by more consistent loading and significantly greater concentrations downstream of the WWTP and during low-flow seasons. In contrast, acetaminophen, trimethoprim, DEET, caffeine, cotinine, and mecoprop patterns demonstrated both seasonally-variable non-WWTP-associated and continual WWTP-associated influences. Surface water studies of CECs often target areas near WWTPs. This study suggests that several CECs often characterized as effluent-associated have additional important sources such as septic systems or land-applied biosolids. Finally, agricultural herbicide (atrazine, acetochlor, and metolachlor) profiles were strongly influenced by agricultural land use and seasonal application-runoff, evident by significantly greater concentrations and loadings at upstream sites and in early summer when application and precipitation rates are greatest. Our results indicate that CEC monitoring studies should consider a range of land uses, seasonality, and transport pathways in relation to concentrations and loadings. This knowledge can augment CEC monitoring programs to result in more accurate source, occurrence, and ecological risk characterizations, more precisely targeted mitigation initiatives, and ultimately, enhanced environmental decision-making. PMID- 26897404 TI - Potential arsenic exposures in 25 species of zoo animals living in CCA-wood enclosures. AB - Animal enclosures are often constructed from wood treated with the pesticide chromated copper arsenate (CCA), which leaches arsenic (As) into adjacent soil during normal weathering. This study evaluated potential pathways of As exposure in 25 species of zoo animals living in CCA-wood enclosures. We analyzed As speciation in complete animal foods, dislodgeable As from CCA-wood, and As levels in enclosure soils, as well as As levels in biomarkers of 9 species of crocodilians (eggs), 4 species of birds (feathers), 1 primate species (hair), and 1 porcupine species (quills). Elevated soil As in samples from 17 enclosures was observed at 1.0-110mg/kg, and enclosures housing threatened and endangered species had As levels higher than USEPA's risk-based Eco-SSL for birds and mammals of 43 and 46mg/kg. Wipe samples of CCA-wood on which primates sit had dislodgeable As residues of 4.6-111MUg/100cm(2), typical of unsealed CCA-wood. Inorganic As doses from animal foods were estimated at 0.22-7.8MUg/kg bw/d. Some As levels in bird feathers and crocodilian eggs were higher than prior studies on wild species. However, hair from marmosets had 6.37mg/kg As, 30-fold greater than the reference value, possibly due to their inability to methylate inorganic As. Our data suggested that elevated As in soils and dislodgeable As from CCA-wood could be important sources of As exposure for zoo animals. PMID- 26897406 TI - Short-time phosphorus losses by overland flow in burnt pine and eucalypt plantations in north-central Portugal: A study at micro-plot scale. AB - Over the past decades, wildfires have affected vast areas of Mediterranean ecosystems leading to a variety of negative on- and off-site environmental impacts. Research on fire-affected areas has given more attention to sediment losses by fire-enhanced overland flow than to nutrient exports, especially in the Mediterranean region. To address this knowledge gap for post-fire losses of phosphorus (P) by overland flow, a recently burnt forest area in north-central Portugal was selected and instrumented immediately after a wildfire. Three slopes were selected for their contrasting forest types (eucalypt vs. pine) and parent materials (granite vs. schist). The selected study sites were a eucalypt site on granite (BEG), a eucalypt site on schist (BES) and a maritime pine site on schist (BPS). Micro-plots were monitored over a period of six months, i.e. till the construction of terraces for reforestation obliged to the removal of the plots. During this 6-month period, overland flow samples were collected at 1- to 2 weekly intervals, depending on rainfall. Total P and PO4-P losses differed markedly between the two types of forests on schist, being lower at the pine site than at the eucalypt site, probably due to the presence of a protective layer of pine needle cast. Parent material did not play an important role in PO4-P losses by overland flow but it did in TP losses, with significantly lower values at the eucalypt site on granite than that on schist. These differences in TP losses can be attributed to the coarser texture of granite soils, typically promoting infiltration and decreasing runoff. The present findings provided further insights into the spatial and temporal patterns of post-fire soil nutrient losses in fire-prone forest types during the initial stages of the window-of disturbance, which can be useful for defining post-fire emergency measures to reduce the risk of soil fertility losses. PMID- 26897407 TI - Understanding the fate of organic micropollutants in sand and granular activated carbon biofiltration systems. AB - In this study, sand and granular activated carbon (GAC) biofilters were comparatively assessed as post-treatment technologies of secondary effluents, including the fate of 18 organic micropollutants (OMPs). To determine the contribution of adsorption and biotransformation in OMP removal, four reactors were operated (two biofilters (with biological activity) and two filters (without biological activity)). In addition, the influence of empty bed contact time (EBCT), ranging from 0.012 to 3.2d, and type of secondary effluent (anaerobic and aerobic) were evaluated. Organic matter, ammonium and nitrate were removed in both biofilters, being their adsorption higher on GAC than on sand. According to the behaviour exhibited, OMPs were classified in three different categories: I) biotransformation and high adsorption on GAC and sand (galaxolide, tonalide, celestolide and triclosan), II) biotransformation, high adsorption on GAC but low or null adsorption on sand (ibuprofen, naproxen, fluoxetine, erythromycin, roxythromycim, sulfamethoxazole, trimethoprim, bisphenol A, estrone, 17beta estradiol and 17alpha-ethinylestradiol), and, III) only adsorption on GAC (carbamazepine, diazepam and diclofenac). No influence of EBCT (in the range tested) and type of secondary effluent was observed in GAC reactors, whereas saturation and kinetic limitation of biotransformation were observed in sand reactors. Taking into account that most of the organic micropollutants studied (around 60%) fell into category II, biotransformation is crucial for the elimination of OMPs in sand biofilters. PMID- 26897405 TI - Potential sources and racial disparities in the residential distribution of soil arsenic and lead among pregnant women. AB - Exposure to arsenic (As) or lead (Pb) has been associated with adverse health outcomes, and high-risk populations can be disproportionately exposed to these metals in soils. The objectives of this study were: to examine if predicted soil As and Pb concentrations at maternal residences of South Carolina (SC) low-income mothers differed based on maternal race (non-Hispanic black versus white), to examine whether differences in predicted residential soil As and Pb concentrations among black and white mothers differed by socioeconomic status (SES), and to examine whether such disparities persisted after controlling for anthropogenic sources of these metals, including direction from, and distance to industrial facilities. Kriged soil As and Pb concentrations were estimated at maternal residences in 11 locations in SC, and models with maternal race and individual and US Census block group level SES measures were examined. US Environmental Protection Agency Toxics Release Inventory (TRI) facility As and Pb releases categorized by distance and direction to block groups in which mothers resided were also identified, as were proxy measures for historic use of leaded gasoline (road density) and Pb-based paint (categories of median year home built by US Census block group). Consistent racial disparities were observed for predicted residential soil As and Pb concentrations, and the disparity was stronger for Pb than As (betas from adjusted models for black mothers were 0.12 and 2.2 for As and Pb, respectively, all p<0.006). Higher road density and older homes in block groups were more closely associated with higher predicted soil As and Pb concentrations than on-site releases of As and Pb categorized by facility location. These findings suggest that non-Hispanic black mothers in this study population had elevated residential As and Pb soil concentrations, after adjusting for SES, and that soil As and Pb concentrations were not associated with recent industrial releases. PMID- 26897408 TI - Evaluation of toxicity and genotoxicity of 2-chlorophenol on bacteria, fish and human cells. AB - Due to the extensive use of chlorophenols (CPs) in anthropogenic activities, 2 Chlorophenol (2-CP), among other CPs, can enter aquatic ecosystems and can be harmful to a variety of organisms, including bacteria, fish and humans, that are exposed directly and/or indirectly to such contaminated environments. Based on the existing knowledge and in order to move a step forward, the purpose of this study is to investigate the toxic and mainly the genotoxic effects of 2-CP using a combination of bioassays. The tests include the marine bacterium Vibrio fischeri and micronuclei induction in the erythrocytes of Carassius auratus as well as in cultured human lymphocytes. The results obtained reveal that 2-CP is able to induce dose-dependent toxic and genotoxic effects on the selected tested concentrations under the specific experimental conditions. PMID- 26897410 TI - Coupling a continuous watershed-scale microbial fate and transport model with a stochastic dose-response model to estimate risk of illness in an urban watershed. AB - Within the United States, elevated levels of fecal indicator bacteria (FIB) remain the leading cause of surface water-quality impairments requiring formal remediation plans under the federal Clean Water Act's Total Maximum Daily Load (TMDL) program. The sufficiency of compliance with numerical FIB criteria as the targeted endpoint of TMDL remediation plans may be questionable given poor correlations between FIB and pathogenic microorganisms and varying degrees of risk associated with exposure to different fecal pollution sources (e.g. human vs animal). The present study linked a watershed-scale FIB fate and transport model with a dose-response model to continuously predict human health risks via quantitative microbial risk assessment (QMRA), for comparison to regulatory benchmarks. This process permitted comparison of risks associated with different fecal pollution sources in an impaired urban watershed in order to identify remediation priorities. Results indicate that total human illness risks were consistently higher than the regulatory benchmark of 36 illnesses/1000 people for the study watershed, even when the predicted FIB levels were in compliance with the Escherichia coli geometric mean standard of 126CFU/100mL. Sanitary sewer overflows were associated with the greatest risk of illness. This is of particular concern, given increasing indications that sewer leakage is ubiquitous in urban areas, yet not typically fully accounted for during TMDL development. Uncertainty analysis suggested the accuracy of risk estimates would be improved by more detailed knowledge of site-specific pathogen presence and densities. While previous applications of the QMRA process to impaired waterways have mostly focused on single storm events or hypothetical situations, the continuous modeling framework presented in this study could be integrated into long-term water quality management planning, especially the United States' TMDL program, providing greater clarity to watershed stakeholders and decision-makers. PMID- 26897409 TI - Dioxins, PCBs, chlorinated pesticides and brominated flame retardants in free range chicken eggs from peri-urban areas in Arusha, Tanzania: Levels and implications for human health. AB - The environment in the northern part of Tanzania is influenced by rapid population growth, and increased urbanization. Urban agriculture is common and of economic value for low income families. In Arusha, many households sell eggs from free-ranging backyard chicken. In 2011, 159 eggs from different households in five different locations in Arusha were collected, homogenized, pooled into 28 composite samples and analyzed for a wide selection of POPs. Levels of POPs varied widely within and between the locations. The levels of dieldrin and SigmaDDT ranged between 2 and 98,791 and 2 and 324ng/g lipid weight (lw), respectively. EU MRLs of 0.02mg/kg dieldrin for eggs were exceeded in 4/28 samples. PCBs, HCHs, chlordanes, toxaphenes and endosulfanes were found at lower frequency and levels. Brominated flame retardants (BFRs), e.g polybrominated diphenylethers (PBDEs), hexabromocyclododecane (HBCD) and 1,2-bis(2,4,6 tribromphenoxy)ethane (BTBPE) were present in 100%, 60% and 46% of the composite samples, respectively. Octa-and deca-BDEs were the dominating PBDEs and BDE 209 levels ranged between 0.81 or >2.64 could identify dogs in the M/T or T groups, respectively. Therefore, GGT/UC might be useful for the management of leishmaniotic dogs. PMID- 26897436 TI - Difficult airway management using the Pentax-AWS Airwayscope with a thin Intlock and bronchofiberscope in a patient with Coffin-Lowry syndrome. PMID- 26897437 TI - A rare case of accidental arterial local anesthetic injection under ultrasound guided stellate ganglion block. PMID- 26897438 TI - An approach to using central pupils as a clinical sign to assess depth of anesthesia in infants undergoing fundus examination with inhalation of sevoflurane. AB - STUDY OBJECTIVE: To determine whether depth of anesthesia correlates with central pupils in outpatient infants undergoing fundus examination during general anesthesia. DESIGN: Prospective, clinical comparison study. SETTING: Outpatient operating room of a university-affiliated hospital. PATIENTS: Premature infants with corrected gestational ages of 44 - 64weeks, who met the criteria for screening for eye examination for retinopathy. INTERVENTIONS: Body movement and central pupils were used as clinical signs. Patients were assigned to one of two groups: the body movement group (Group M) and the central pupils group (Group C). Anesthesia was induced with inhalation of 6% sevoflurane, and time to loss of movement was recorded as the induction time. Following induction, the inspired concentration of sevoflurane was adjusted to the maintenance concentration. The up-and-down method was used to determine the subsequent concentration. The initial maintenance concentration was 3% in both groups. In Group M, no movement response was recorded as (+) while movement response was recorded as (-). The gradient of increase or decrease was 0.5%. If the preceding subject did not move, the sevoflurane maintenance concentration was decreased by 0.5%. In Group C, the central pupils were recorded as (+) and non-central pupils were recorded as (-). The method used to determine the sevoflurane concentration given to premature infants in Group C was the same as in Group M. MEASUREMENT: Induction time, anesthesia duration, and time to recovery after anesthesia were recorded. The presence of purposeful movement and central pupils were recorded in both groups. MAIN RESULT: 27 pediatric outpatients completed the investigation in Group M, and the effective inhalation concentrations in 5650% of patients (EIC50) value of sevoflurane was 3.0%. Thirty-one patients completed the investigation in Group C, and the EIC50 value of sevoflurane was 3.4%. The pediatric outpatients with central fixation of the pupils did not move during the examination. CONCLUSION: Central pupils are a reliable clinical indicator to assess adequate anesthetic depth in preterm infants during sevoflurane anesthesia. PMID- 26897440 TI - Detection of large perforating artery by ultrasound prescan before obturator nerve block. PMID- 26897439 TI - Effect of laryngotracheal topical anesthesia on recurrent laryngeal nerve monitoring during thyroid Surgery. AB - STUDY OBJECTIVE: Intraoperative neuromonitoring of the recurrent laryngeal nerve (RLN) is often used as an adjunct for RLN identification and preservation during thyroidectomies. Laryngotracheal anesthesia (LTA) with topical lidocaine reduces coughing upon emergence from anesthesia and in the immediate postoperative period; however, its use is prohibited with concerns that it could decrease the sensitivity of the intraoperative neuromonitoring. We hypothesize that there is no difference in measurements of nerve conduction made before and after LTA administration. DESIGN: An observational study in which all patients were subjected to LTA administration was conducted. Recurrent laryngeal nerve threshold currents were measured before and after the intervention. SETTING: Tertiary medical center operating room. PATIENTS: Eighteen patients (total of 25 nerves at risk) with American Society of Anesthesiologists classes 1 to 3 undergoing thyroid surgery. INTERVENTIONS: After the thyroid was removed and threshold currents at the RLN were obtained, LTA with endotracheal lidocaine was applied on the left and right side of the in situ endotracheal tube (2 cc of 4% lidocaine per side). Threshold currents were reassessed at 5 and 10 minutes after LTA administration. MEASUREMENTS: Threshold currents (minimum stimulus current applied to the RLN required to generate a discernible electromyographic response at the vocal cords) were recorded along the RLN for a baseline at 5 and 10 mm from the insertion point of the RLN into the larynx. Threshold currents were reassessed at the same 2 positions on the RLN at 5 and 10 minutes after LTA administration. Differences in mean values, between threshold currents recorded at the 3 different times, at 2 positions on the RLN, were used to compare effects of LTA on nerve conduction. MAIN RESULTS: There were no statistically significant differences when comparing threshold currents before and after LTA administration. CONCLUSIONS: Laryngotracheal anesthesia had no significant effect on RLN nerve conduction in the period assessed. PMID- 26897442 TI - Congenital lobar emphysema and tension emphysema. PMID- 26897441 TI - Assessing change trends over time in preoperative comorbidities and postoperative complications after total knee arthroplasty. PMID- 26897444 TI - Intravenous labetolol in treating hypertensive crisis following dexmedetomidine infusion for procedural sedation. AB - Dexmedetomidine is widely used for procedural sedation because of its unique combination of sedation, analgesia, and anxiolysis with minimal respiratory depression. Transient hypertension has been reported during the use of dexmedetomidine which is usually benign and is taken over by the hypotensive response on continuing the infusion. We report a case of hypertensive crisis following dexmedetomidine infusion used for procedural sedation, necessitating discontinuation of the infusion and treatment of hypertension. The dilemmas involved in treating hypertension caused by dexmedetomidine are discussed. PMID- 26897443 TI - The intraoperative glycemic response to intravenous insulin during noncardiac surgery: a subanalysis of the DeLiT randomized trial. AB - Patient characteristics may affect patients' response to insulin. We examined the impact of body weight and presence of diabetes on the response to insulin during noncardiac surgery. We studied 202 patients who were enrolled in the DeLiT Trial and received intraoperative intravenous insulin. Univariable and multivariable analyses (Bonferroni corrected) assessed the relationship between patient's response to the initial intraoperative I.V. bolus of regular insulin and the factors of interest. Blood glucose concentrations decreased 8.3 +/- 10mg/dL (0.46 +/- 0.56mmol/L) per unit of I.V. insulin in 30minutes. The response to insulin was similar in patients with or without diabetes (adjusted mean difference [97.5% confidence interval], 0.2 [-3.9, 4.2] mg/dL, 0.01 [-0.22, 0.24] mmol/L; P = .93). No relationship was found between insulin response and body weight (P=0.38). Our results suggest that adjustment for body weight and the presence of diabetes may not improve intraoperative insulin treatment algorithms. PMID- 26897446 TI - Evaluation of double-lumen endotracheal tube extubation force by extraction angle: a prospective randomized clinical trial. AB - STUDY OBJECTIVE: Gentle and noninvasive double-lumen tracheal tube (DLT) extubation is important for both airway and circulatory management, especially after lung resection. We performed a prospective randomized clinical trial comparing DLT extubation force based on 2 different extraction angles. DESIGN: Randomized clinical trial. SETTING: Operating room. PATIENTS: Sixty adult patients scheduled for elective surgery under general anesthesia using DLT with ASA physical status 1 to 3. INTERVENTIONS: Sixty patients who underwent lung resection with a DLT were randomly assigned to extraction angles of 60 degrees (30 patients) and 90 degrees (30 patients) relative to the ground. MEASUREMENTS: Extubation forces and changes in vital signs were compared between groups. Results were analysed with the Mann-Whitney U test, non-paired t test, and chi(2) test. P<.05 was considered significant. MAIN RESULTS: Less extraction force was needed at 60 degrees compared to 90 degrees (90 degrees , 13.9+/-2.3 N; 60 degrees ; 7.1+/-2.1 N; P<.001). The rate of increase in systolic and diastolic blood pressure (post-extubation/pre-extubation) was significantly smaller at 60 degrees than at 90 degrees (systolic blood pressure, P<.001; diastolic blood pressure, P=.002). CONCLUSIONS: Our findings suggest that DLT extubation at 60 degrees requires less force than at 90 degrees and was accompanied by a smaller increase in blood pressure. Thus, extraction at 60 degrees may be less invasive and beneficial for patients undergoing DLT extubation. PMID- 26897447 TI - Use of a bite block to manage the airway of a patient with masticatory muscle tendon-aponeurosis hyperplasia. PMID- 26897445 TI - Peripheral nerve blocks with sedation using propofol and alfentanil target controlled infusion for hip fracture surgery: a review of 6 years in use. AB - BACKGROUND AND OBJECTIVES: Over the last 6 years, our center has introduced a novel technique combining peripheral nerve blocks (femoral and lateral femoral cutaneous nerves) with sedation using propofol with alfentanil target-controlled infusion for hip fracture surgery. The purpose of this review was to identify if adverse outcomes (of mortality and length of stay) were associated with its introduction compared to spinal or general anesthesia. METHODS: Retrospective data collection from hospital fracture database. Data were analyzed using Cox regression (adjusted for age, sex, and American Society of Anesthesiologists grade) to compare survival and length of stay data across the different anesthetic techniques used for hip fracture surgery. RESULTS: This technique was used in 472 (20%) of 2360 hip fractures. There was no significant difference between peripheral nerve blocks with propofol/alfentanil sedation/analgesia for mortality up to 120days (hazard ratio, 0.76; 95% confidence interval, 0.54-1.06; P=.11) and length of stay (hazard ratio, 1.03; 95% confidence interval, 0.91 1.17; P=.63) when compared to the other anesthetic techniques of spinal and general anesthesia. CONCLUSION: This novel technique does not appear to be associated with adverse mortality or length of stay after hip fracture surgery. PMID- 26897448 TI - One-lung ventilation after rapid-sequence intubation: a novel approach using an ETView tracheoscopic ventilation tube for placement of an EZ-Blocker without bronchoscopy. PMID- 26897449 TI - Peripheral nerve blocks in patients with Ehlers-Danlos syndrome, hypermobility type: a report of 2 cases. AB - Ehlers-Danlos syndrome is an inherited disorder of collagen production that results in multiorgan dysfunction. Patients with hypermobility type display skin hyperextensibility and joint laxity, which can result in chronic joint instability, dislocation, peripheral neuropathy, and severe musculoskeletal pain. A bleeding diathesis can be found in all subtypes of varying severity despite a normal coagulation profile. There have also been reports of resistance to local anesthetics in these patients. Several sources advise against the use of regional anesthesia in these patients citing the 2 previous features. There have been reports of successful neuraxial anesthesia, but few concerning peripheral nerve blocks, none of which describe nerves of the lower extremity. This report describes 2 cases of successful peripheral regional anesthesia in the lower extremity. In case 1, a 16-year-old adolescent girl with hypermobility type presented for osteochondral grafting of tibiotalar joint lesions. She underwent a popliteal sciatic (with continuous catheter) and femoral nerve block under ultrasound guidance. She proceeded to surgery and tolerated the procedure under regional block and intravenous sedation. She did not require any analgesics for the following 15 hours. In case 2, an 18-year-old woman with hypermobility type presented for medial patellofemoral ligament reconstruction for chronic patella instability. She underwent a saphenous nerve block above the knee with analgesia in the distribution of the saphenous nerve lasting for approximately 18 hours. There were no complications in either case. Prohibitions against peripheral nerve blocks in patients with Ehlers-Danlos syndrome, hypermobility type, appear unwarranted. PMID- 26897450 TI - Effectiveness of integrating individualized and generic complementary medicine treatments with standard care versus standard care alone for reducing preoperative anxiety. AB - STUDY OBJECTIVE: Preoperative anxiety is commonly reported by people undergoing surgery. A significant number of studies have found a correlation between preoperative anxiety and post-operative morbidity. Various methods of complementary and alternative medicine (CAM) were found to be effective in alleviating preoperative anxiety. This study examined the relative effectiveness of various individual and generic CAM methods combined with standard treatment (ST) in relieving preoperative anxiety, in comparison with ST alone. DESIGN: Randomized controlled trial. SETTING: Holding room area PATIENTS: Three hundred sixty patients. INTERVENTIONS: Patients were randomly divided into 6 equal-sized groups. Group 1 received the standard treatment (ST) for anxiety alleviation with anxiolytics. The five other groups received the following, together with ST (anxiolytics): Compact Disk Recording of Guided Imagery (CDRGI); acupuncture; individual guided imagery; reflexology; and individual guided imagery combined with reflexology, based on medical staff availability. MEASUREMENTS: Assessment of anxiety was taken upon entering the holding room area (surgery preparation room) ('pre-treatment assessment'), and following the treatment, shortly before transfer to the operating room ('post-treatment assessment'), based on the Visual Analogue Scale (VAS) questionnaire. Data processing included comparison of VAS averages in the 'pre' and 'post' stages among the various groups. MAIN RESULTS: Preoperatively, CAM treatments were associated with significant reduction of anxiety level (5.54-2.32, p<0.0001). In contrast, no significant change was noted in the standard treatment group (4.92-5.44, p=0.15). Individualized CAM treatments did not differ significantly in outcomes. However, CDRGI was less effective than individualized CAM (P<0.001), but better than ST (p=0.005). CONCLUSIONS: Individual CAM treatments integrated within ST reduce preoperative anxiety significantly, compared to standard treatment alone, and are more effective than generic CDRGI. In light of the scope of preoperative anxiety and its implications for public health, integration of CAM therapies with ST should be considered for reducing preoperative anxiety. PMID- 26897451 TI - Comparison of recovery parameters for xenon versus other inhalation anesthetics: systematic review and meta-analysis. AB - STUDY OBJECTIVE: To summarize and evaluate the available data describing the recovery parameters of xenon anesthesia. DESIGN: Systematic review and meta analysis. SETTING: Anesthesia for elective surgeries. PATIENTS: Systematic review of randomized controlled trials (RCTs) from databases including Medline (1964 2013), the Cochrane Central Register of Controlled Trials (CENTRAL, 1990-2012), and Google Scholar (1966-2013). INTERVENTIONS: Inhalation of xenon or other anesthetics was administered in elective surgery. MEASUREMENTS: Recovery parameters (time to recovery, alertness/sedation scale scores at "eye opening," bispectral index at "reaction on demand," time to extubation, and time to orientation). MAIN RESULTS: Eleven RCTs (N = 661 patients) met the inclusion criteria. Recovery from xenon anesthesia was significantly faster in terms of the time to eye opening (mean difference [MD], -4.18 minutes; 95% confidence interval [CI], -5.03 to -3.32 minutes; P < .00001), the time to reaction on demand (MD, 5.35 minutes; 95% CI, -6.59 to -4.11 minutes; P < .00001), the time to extubation (MD, -4.49 minutes; 95% CI, -5.40 to -3.58 minutes; P < .00001), and the time to orientation (MD, -4.99 minutes; 95% CI, -6.45 to -3.52 minutes; P < .00001). CONCLUSIONS: This meta-analysis confirmed that recovery from xenon anesthesia is faster than other inhalation anesthesia. PMID- 26897452 TI - A pilot study of upper airway management using a remote-controlled artificial muscle device during propofol anesthesia. AB - STUDY OBJECTIVE: To test the hypothesis that the jaw closure using a pneumatic actuator device affect airway collapsibility and resistance during propofol anesthesia. DESIGN: Prospective, randomized study. SETTING: University-affiliated hospital. PATIENTS: Six male subjects were included in the present study. INTERVENTION: We used pressure-flow relationships to evaluate critical closing pressure (PCRIT) and upper airway resistance in different conditions of body and head position. Anesthesia was induced and maintained with a propofol infusion, targeting a constant blood concentration of 1.5 to 2.0MUg/mL to establish an adequate depth of anesthesia, with patients breathing spontaneously through a nasal mask. An air-inflatable pneumatic actuator was used to achieve jaw closure. Nasal mask pressure was intermittently reduced to evaluate upper airway collapsibility (passive PCRIT) and upstream resistance under 4 different conditions: (1) neutral occlusion at 0-cm head elevation (baseline), (2) jaw closure at 0-cm head elevation, (3) neutral occlusion at 6-cm head elevation, and (4) jaw closure at 6-cm head elevation. PCRIT and upstream resistance under each condition were compared using 1-way analysis of variance. P<.05 was considered significant. MEASUREMENTS: The pressure and inspiratory flow at the subjects' nose mask were recorded. Polysomonographic parameters (electroencephalograms, electrooculograms, submental electromyograms, and plethysmogram) were also recorded. MAIN RESULTS: The combination of 6-cm head elevation with jaw closure using the pneumatic actuator decreased upper airway collapsibility (PCRIT~-3.0 cm H2O) compared to the baseline position (PCRIT~-1.2 cm H2O; P=.0003). CONCLUSION: We demonstrated that jaw closure using an air-inflatable pneumatic actuator device can produce substantial decreases in upper airway collapsibility and maintain upper airway patency during propofol anesthesia. PMID- 26897453 TI - The ultrasound-guided transversus thoracic muscle plane block is effective for the median sternotomy. PMID- 26897454 TI - Development, acceptability and efficacy of a standardized healthy lifestyle intervention in recurrent depression. AB - BACKGROUND: Research evidence on the effects of integrated multifaceted lifestyle interventions for depression is scanty. The aim of the present study is to report on the development, acceptability and efficacy of a standardized healthy lifestyle intervention, including exercise, eating habits, sleep hygiene and smoking cessation in preventing relapses. METHODS: One hundred-sixty outpatients with recurrent unipolar depression or bipolar disorder were recruited after achieving full remission or recovery from the most recent depressive episode. Patients were randomized to 3-months of usual care or to an intervention aimed at promoting a healthy lifestyle (HLI), as an augmentation of pharmacological maintenance treatment. Usual care consisted of clinical management visits. At the end of the intervention, follow-up visits were scheduled at 3,6,9 and 12 months. RESULTS: During the intervention phase, 1 relapse occurred in the HLI group and 4 in the control group. Over the 12 months of follow-up, relapses were 5 in the HLI group and 16 in control group. Using an intent-to-treat approach, the overall percentage of relapses was 6/81 (7.4%) in the HLI group vs. 20/79 (25.3%) in the control group.. In a Kaplan-Meier survival analysis the risk of relapse was significantly lower in patients receiving the HLI intervention (log-rank test, p=0.003) over the 60 weeks of observation. The majority of patients assigned to HLI adhered to the program, and were highly motivated throughout the intervention. LIMITATIONS: The retention rate was low because patients were recruited during the maintenance phase and the 1-year follow-up was relatively short to detect a long-term effect of HLI. CONCLUSIONS: The HLI program proved to be efficacious in preventing relapses. Given the absence of contraindications and its cost-effectiveness in routine practice, the use of HLI should be encouraged to promote the well-being of patients with recurrent depression. PMID- 26897455 TI - A comparative meta-analysis of TEMPS scores across mood disorder patients, their first-degree relatives, healthy controls, and other psychiatric disorders. AB - BACKGROUND: The Temperament Evaluation Memphis, Pisa, Paris and San Diego Auto questionnaire (TEMPS) is validated to assess temperament in clinical and non clinical samples. Scores vary across bipolar disorder (BD), major depressive disorder (MDD), attention-deficit/hyperactivity disorder (ADHD), borderline personality disorder (BPD) and healthy controls (HCs), but a meta-analysis is missing. METHODS: Meta-analysis of studies comparing TEMPS scores in patients with mood disorders or their first-degree relatives to each other, or to a psychiatric control group or HCs. RESULTS: Twenty-six studies were meta-analyzed with patients with BD (n= 2025), MDD (n=1283), ADHD (n=56) and BPD (n=43), relatives of BD (n=436), and HCs (n=1757). Cyclothymic (p<0.001) and irritable TEMPS scores (p<0.001) were higher in BD than MDD (studies=12), and in MDD vs HCs (studies=8). Cyclothymic (p<0.001), irritable (p<0.001) and anxious (p=0.03) scores were higher in BD than their relatives, who, had higher scores than HCs. No significant differences emerged between ADHD and BD (studies=3); CONCLUSION: Affective temperaments are on a continuum, with increasing scores ranging from HCs through MDD to BD regarding cyclothymic and irritable temperament, from MDD through BD to HC regarding hyperthymic temperament, and from HC through BD relatives to BD regarding cyclothymic, irritable and anxious temperament. Depressive and anxious temperaments did not differ between BD and MDD, being nonetheless the lowest in HCs. BD did not differ from ADHD in any investigated TEMPS domain. LIMITATIONS: Different TEMPS versions, few studies comparing BD with ADHD or BPD, no correlation with other questionnaires. PMID- 26897456 TI - Morningness-eveningness and depressive symptoms: Test on the components level with CES-D in Polish students. AB - BACKGROUND: The study aimed to elucidate previously observed associations between morningness-eveningness and depressive symptomatology in university students. Relations between components of depressive symptomatology and morningness eveningness were analysed. METHODS: Nine hundred and seventy-four university students completed Polish versions of the Centre for Epidemiological Studies - Depression scale (CES-D; Polish translation appended to this paper) and the Composite Scale of Morningness. Principal component analysis (PCA) was used to test the structure of depressive symptoms. Pearson and partial correlations (with age and sex controlled), along with regression analyses with morning affect (MA) and circadian preference as predictors, were used. RESULTS: PCA revealed three components of depressive symptoms: depressed/somatic affect, positive affect, interpersonal relations. Greater MA was related to less depressive symptoms in three components. Morning circadian preference was related to less depressive symptoms in depressed/somatic and positive affects and unrelated to interpersonal relations. Both morningness-eveningness components exhibited stronger links with depressed/somatic and positive affects than with interpersonal relations. Three CES-D components exhibited stronger links with MA than with circadian preference. In regression analyses only MA was statistically significant for positive affect and better interpersonal relations, whereas more depressed/somatic affect was predicted by lower MA and morning circadian preference (relationship reversed compared to correlations). LIMITATIONS: Self-report assessment. CONCLUSIONS: There are three groups of depressive symptoms in Polish university students. Associations of MA with depressed/somatic and positive affects are primarily responsible for the observed links between morningness-eveningness and depressive symptoms in university students. People with evening circadian preference whose MA is not lowered have less depressed/somatic affect. PMID- 26897457 TI - EU Regulations Impede Market Introduction of GM Forest Trees. AB - Biotechnology can greatly improve the efficiency of forest tree breeding for the production of biomass, energy, and materials. However, EU regulations impede the market introduction of genetically modified (GM) trees so their socioeconomic and environmental benefits are not realized. European policy makers should concentrate on a science-based regulatory process. PMID- 26897458 TI - Rapid and simple method for in vivo ex utero development of mouse embryo explants. AB - The in utero development of mammals drastically reduces the accessibility of the mammalian embryo and therefore limits the range of experimental manipulation that can be done to study functions of genes or signaling pathways during embryo development. Over the past decades, tissue and organ-like culture methods have been developed with the intention of reproducing in vivo situations. Developing accessible and simple techniques to study and manipulate embryos is an everlasting challenge. Herein, we describe a reliable and quick technique to culture mid-gestation explanted mouse embryos on top of a floating membrane filter in a defined medium. Viability of the cultured tissues was assessed by apoptosis and proliferation analysis showing that cell proliferation is normal and there is only a slight increase in apoptosis after 12h of culture compared to embryos developing in utero. Moreover, differentiation and morphogenesis proceed normally as assessed by 3D imaging of the transformation of the myotome into deep back muscles. Not only does muscle cell differentiation occur as expected, but so do extracellular matrix organization and the characteristic splitting of the myotome into the three epaxial muscle groups. Our culture method allows for the culture and manipulation of mammalian embryo explants in a very efficient way, and it permits the manipulation of in vivo developmental events in a controlled environment. Explants grown under these ex utero conditions simulate real developmental events that occur in utero. PMID- 26897460 TI - Multimodal imaging in an unusual case of radionecrosis of the pubic symphysis. PMID- 26897459 TI - A novel conditional mouse model for Nkx2-5 reveals transcriptional regulation of cardiac ion channels. AB - Nkx2-5 is one of the master regulators of cardiac development, homeostasis and disease. This transcription factor has been previously associated with a suite of cardiac congenital malformations and impairment of electrical activity. When disease causative mutations in transcription factors are considered, NKX2-5 gene dysfunction is the most common abnormality found in patients. Here we describe a novel mouse model and subsequent implications of Nkx2-5 loss for aspects of myocardial electrical activity. In this work we have engineered a new Nkx2-5 conditional knockout mouse in which flox sites flank the entire Nkx2-5 locus, and validated this line for the study of heart development, differentiation and disease using a full deletion strategy. While our homozygous knockout mice show typical embryonic malformations previously described for the lack of the Nkx2-5 gene, hearts of heterozygous adult mice show moderate morphological and functional abnormalities that are sufficient to sustain blood supply demands under homeostatic conditions. This study further reveals intriguing aspects of Nkx2-5 function in the control of cardiac electrical activity. Using a combination of mouse genetics, biochemistry, molecular and cell biology, we demonstrate that Nkx2-5 regulates the gene encoding Kcnh2 channel and others, shedding light on potential mechanisms generating electrical abnormalities observed in patients bearing NKX2-5 dysfunction and opening opportunities to the study of novel therapeutic targets for anti-arrhythmogenic therapies. PMID- 26897461 TI - Solitary fibrous breast tumour: Contribution of 18F-FDG PET/CT. PMID- 26897462 TI - Sociodemographic Variables, Clinical Features, and the Role of Preassessment Cross-Sex Hormones in Older Trans People. AB - INTRODUCTION: As referrals to gender identity clinics have increased dramatically over the last few years, no studies focusing on older trans people seeking treatment are available. AIMS: The aim of this study was to investigate the sociodemographic and clinical characteristics of older trans people attending a national service and to investigate the influence of cross-sex hormones (CHT) on psychopathology. METHODS: Individuals over the age of 50 years old referred to a national gender identity clinic during a 30-month period were invited to complete a battery of questionnaires to measure psychopathology and clinical characteristics. Individuals on cross-sex hormones prior to the assessment were compared with those not on treatment for different variables measuring psychopathology. MAIN OUTCOME MEASURES: Sociodemographic and clinical variables and measures of depression and anxiety (Hospital Anxiety and Depression Scale), self-esteem (Rosenberg Self-Esteem Scale), victimization (Experiences of Transphobia Scale), social support (Multidimensional Scale of Perceived Social Support), interpersonal functioning (Inventory of Interpersonal Problems), and nonsuicidal self-injury (Self-Injury Questionnaire). RESULTS: The sex ratio of trans females aged 50 years and older compared to trans males was 23.7:1. Trans males were removed for the analysis due to their small number (n = 3). Participants included 71 trans females over the age of 50, of whom the vast majority were white, employed or retired, and divorced and had children. Trans females on CHT who came out as trans and transitioned at an earlier age were significantly less anxious, reported higher levels of self-esteem, and presented with fewer socialization problems. When controlling for socialization problems, differences in levels of anxiety but not self-esteem remained. CONCLUSION: The use of cross-sex hormones prior to seeking treatment is widespread among older trans females and appears to be associated with psychological benefits. Existing barriers to access CHT for older trans people may need to be re-examined. PMID- 26897463 TI - Use of claims data to estimate annual cervical cancer screening percentages in Portland metropolitan area, Oregon. AB - BACKGROUND: Human papillomavirus (HPV) vaccine should reduce cervical dysplasia before cervical cancer. However, dysplasia diagnosis is screening-dependent. Accurate screening estimates are needed. PURPOSE: To estimate the percentage of women in a geographic population that has had cervical cancer screening. METHODS: We analyzed claims data for (Papanicolau) Pap tests from 2008-2012 to estimate the percentage of insured women aged 18-39 years screened. We estimated screening in uninsured women by dividing the percentage of insured Behavioral Risk Factor Surveillance Survey respondents reporting previous-year testing by the percentage of uninsured respondents reporting previous-year testing, and multiplying this ratio by claims-based estimates of insured women with previous-year screening. We calculated a simple weighted average of the two estimates to estimate overall screening percentage. We estimated credible intervals using Monte-Carlo simulations. RESULTS: During 2008-2012, an annual average of 29.6% of women aged 18-39 years were screened. Screening increased from 2008 to 2009 in all age groups. During 2009-2012, the screening percentages decreased for all groups, but declined most in women aged 18-20 years, from 21.5% to 5.4%. Within age groups, compared to 2009, credible intervals did not overlap during 2011 (except age group 21-29 years) and 2012, and credible intervals in the 18-20 year group did not overlap with older groups in any year. CONCLUSIONS: This introduces a novel method to estimate population-level cervical cancer screening. Overall, percentage of women screened in Portland, Oregon fell following changes in screening recommendations released in 2009 and later modified in 2012. PMID- 26897464 TI - Physicochemical characterization by AFM, FT-IR and DSC and biological assays of a promising antileishmania delivery system loaded with a natural Brazilian product. AB - The control and treatment of Leishmaniasis, a neglected and infectious disease affecting approximately 12 million people worldwide, are challenging. Leishmania parasites multiply intracellularly within macrophages located in deep skin and in visceral tissues, and the currently employed treatments for this disease are subject to significant drawbacks, such as resistance and toxicity. Thus, the search for new Leishmaniasis treatments is compulsory, and Ocotea duckei Vattimo, a plant-derived product from the biodiverse Brazilian flora, may be a promising new treatment for this disease. In this regard, the aim of this work was to develop and characterize a delivery system based on solid lipid nanoparticles (SLN) that contain the liposoluble lignan fraction (LF) of Ocotea duckei Vattimo, which targets the Leishmania phagolysosome of infected macrophages. LF-loaded SLNs were obtained via the hot microemulsion method, and their physical and chemical properties were comprehensively assessed using PCS, AFM, SEM, FT-IR, DSC, HPLC, kinetic drug release studies, and biological assays. The size of the developed delivery system was 218.85+/-14.2 nm, its zeta potential was -30 mV and its entrapment efficiency (EE%) was high (the EEs% of YAN [yangambin] and EPI-YAN [epi-yangambin] markers were 94.21+/-0.40% and 94.20+/-0.00%, respectively). Microscopy, FT-IR and DSC assays confirmed that the delivery system was nanosized and indicated a core-shell encapsulation model, which corroborated the measured kinetics of drug release. The total in vitro release rates of YAN and EPI-YAN in buffer (with sink conditions attained) were 29.6+/-8.3% and 34.3+/-8.9%, respectively, via diffusion through the cellulose acetate membrane of the SLN over a period of 4 h. After 24 h, the release rates of both markers reached approximately 45%, suggesting a sustained pattern of release. Mathematical modeling indicated that both markers, YAN and EPI-YAN, followed matrix diffusion based release kinetics (Higuchi's model) with an estimated diffusion coefficient (D) of 1.3.10(-6) cm(2)/s. The LF-loaded SLNs were non-toxic to murine macrophages (20-80 MUg mL(-1) range) and exerted a prominent anti-leishmanial effect (20 MUg mL(-1)). These data suggest this new and well-characterized lipid nanoparticle delivery system safely and effectively kills Leishmania and warrants further clinical investigation. PMID- 26897465 TI - Synthesis, characterization and application of Au-198 nanoparticles as radiotracer for industrial applications. AB - This paper describes synthesis and characterization of radioactive gold nanoparticles ((198)Au-NPs), and explores their utility as a radiotracer for tracing an aqueous phase in a continuous laboratory-scale bubble column at ambient conditions. The performance of the (198)Au-NPs as a radiotracer was compared with the results obtained with a conventional radiotracer i.e. bromine 82 ((82)Br) as ammonium bromide and found to be identical. A tank-in-series with backmixing model (TISBM) was used to simulate the RTDs of the aqueous phase and characterize flow in the bubble column. PMID- 26897466 TI - F8 gene mutation profile in Indian hemophilia A patients: Identification of 23 novel mutations and factor VIII inhibitor risk association. AB - 'FVIII inhibitors', especially in severe hemophilia A (HA) patients, is a serious adverse effect that complicates their clinical management. Many genetic and non genetic risk factors have been proposed for FVIII inhibitor development, diverse in different population groups. This is the first study in Indian hemophiliacs that analyzes inhibitor risk in relation to the complete F8 mutation profile, in a case-control study that included 145 Indian severe HA patients, i.e. 69 inhibitor positive (with 18 inhibitor concordant/discordant family members), and 58 inhibitor negative patients, after informed consent. While 53.54% (68/127) index cases were positive for intron 22 or intron 1 inversions, 55 causative F8 mutations were detected in the 59 inversion negative patients, of which 23 were novel mutations (in 24 patients) and 32 were reported earlier (in 35 patients). A higher incidence of mutations, in the C1 and C2 domains in inhibitor positive patients, and in the A1 domain in inhibitor negative patients was observed, though not significantly different. The study suggests that large F8 rearrangements (significantly higher in the inhibitor positive patients) pose the highest risk, while missense mutations (significantly higher in the inhibitor negative patients) pose the lowest risk of inhibitor development in Indian hemophilia A patients. PMID- 26897468 TI - Practical Aspects of Monogenic Diabetes: A Clinical Point of View. PMID- 26897467 TI - [3D modeling of the female pelvis by Computer-Assisted Anatomical Dissection: Applications and perspectives]. AB - OBJECTIVES: To achieve a 3D vectorial model of a female pelvis by Computer Assisted Anatomical Dissection and to assess educationnal and surgical applications. MATERIALS AND METHOD: From the database of "visible female" of Visible Human Project((r)) (VHP) of the "national library of medicine" NLM (United States), we used 739 transverse anatomical slices of 0.33mm thickness going from L4 to the trochanters. The manual segmentation of each anatomical structures was done with Winsurf((r)) software version 4.3. Each anatomical element was built as a separate vectorial object. The whole colored-rendered vectorial model with realistic textures was exported in 3Dpdf format to allow a real time interactive manipulation with Acrobat((r)) pro version 11 software. RESULTS: Each element can be handled separately at any transparency, which allows an anatomical learning by systems: skeleton, pelvic organs, urogenital system, arterial and venous vascularization. This 3D anatomical model can be used as data bank to teach of the fundamental anatomy. CONCLUSION: This 3D vectorial model, realistic and interactive constitutes an efficient educational tool for the teaching of the anatomy of the pelvis. 3D printing of the pelvis is possible with the new printers. PMID- 26897469 TI - Effects of total solids content on waste activated sludge thermophilic anaerobic digestion and its sludge dewaterability. AB - The role of total solids content on sludge thermophilic anaerobic digestion was investigated in batch reactors. A range of total solids content from 2% to 10% was evaluated with two replicates. The lowest inhibitory concentration for free ammonia and total ammonia of sludge thermophilic anaerobic digestion was 110.9 171.4mg/L and 1313.1-1806.7mg/L, respectively. The volumetric biogas production rate increased with increasing of total solids content, but the corresponding biogas yield per gram volatile solid decreased. The result of normalized capillary suction time indicated that the dewaterability of digested sludge at high total solids content was poor, while solid content of sediment obtained by centrifuging sludge at 2000g for 10min increased with increasing of total solids content of sludge. The results suggest that thickened sludge mixed with dewatered sludge at an appropriate ratio could get high organic loading rate, high biogas yield and adequate dewatering effort. PMID- 26897470 TI - Removal of metal and organic pollutants from wastewater by a sequential selective technique. AB - In this study the application of a sequential selective system that combined biosorption with biodegradation was evaluated as a feasible process for the removal of Cr(VI) and m-cresol from effluents. Cr(VI) biosorption on pretreated chestnut shells showed 100% metal removal and modelling efforts demonstrated that the pseudo-second order kinetic model and Langmuir isotherm fit well the process behaviour. Thus, the treated stream was an appropriate environment for the biodegradation of m-cresol using a laccase-producer fungus, Phlebia radiata. Two bioreactor configurations, rotating drum and modified-airlift, were studied using the fungus grown on chestnut shells, which act as support-substrate as well as oxidative enzyme inductor increasing the laccase activity up to 1000UL(-1). The best bioreactor, rotating drum, reached 100% removal in 7days. Finally, the best configuration for the sequential selective system was modelled operating in continuous mode by the breakthrough curves generated using FASTv2.0 and the design bioreactor flow model. PMID- 26897471 TI - Modulation of fatty acid metabolism and tricarboxylic acid cycle to enhance the lipstatin production through medium engineering in Streptomyces toxytricini. AB - This work investigated the potential of medium engineering to obtain maximum biomass, non-conventional carbon sources for lipstatin production and modulation of tricarboxylic acid (TCA) cycle to promote lipstatin synthesis. It was found that 2:3 carbon and nitrogen ratio, produced maximum biomass of 7.9g/L in growth medium and 6.6g/L in pre-seed medium. Among the studied non-conventional carbon sources i.e., soya flour 40g/L and sesame oil 30mL/L were found producing 1109.37mg/L (1.24-fold of control) and 1196.75mg/L (1.34-fold of control) lipstatin respectively. Supplementation of TCA cycle intermediates revealed that NADH and succinic acid showed lipstatin production to 1132.99mg/L and 1171.10mg/L respectively. Experimental outcome was validated in 7L bioreactor and produced 2242.63mg/L lipstatin which was ~14% higher than shake flask. PMID- 26897472 TI - Improving the biogas production performance of municipal waste activated sludge via disperser induced microwave disintegration. AB - In this study, the influence of disperser induced microwave pretreatment was investigated to analyze the proficiency of floc disruption on subsequent disintegration and biodegradability process. Initially, the flocs in the sludge was disrupted through disperser at a specific energy input of 25.3kJ/kgTS. The upshot of the microwave disintegration presents that the solids reduction and solubilization of floc disrupted (disperser induced microwave pretreated) sludge was found to be 17.33% and 22% relatively greater than that achieved in microwave pretreated (9.3% and 16%) sludge alone. The biodegradability analysis, affords an evaluation of parameter confidence and correlation determination. The eventual biodegradability of microwave pretreated, and floc disrupted sludges were computed to be 0.15(gCOD/gCOD) and 0.28(gCOD/gCOD), respectively. An economic assessment of this study offers a positive net profit of about 104.8USD/ton of sludge in floc disrupted sample. PMID- 26897473 TI - Using a high biomass plant Pennisetum hydridum to phyto-treat fresh municipal sewage sludge. AB - The study was carried out to investigate the use of a high biomass plant, Pennisetum hydridum, to treat municipal sewage sludge (MSS). An experiment composed of plots with four treatments, soil, fresh sludge, soil-sludge mixture and phyto-treated sludge, was conducted. It showed that the plant could not survive directly in fresh MSS when cultivated from stem cuttings. The experiment transplanting the incubated cutting with nurse medium of P. hydridum in soil and fresh MSS, showed that the plants grew normally in fresh MSS. The pilot experiment of P. hydridum and Alocasia macrorrhiza showed that the total yield and nutrient amount of P. hydridum were 9.2 times and 3.6 times more than that of A. macrorrhiza. After plant treatment, MSS was dried, stabilized and suitable to be landfilled or incinerated, with a calorific value of about 5.6MJ/kg (compared to the initial value of 1.9MJ/kg fresh sludge). PMID- 26897474 TI - Co-composting of gelatin industry sludge combined with organic fraction of municipal solid waste and poultry waste employing zeolite mixed with enriched nitrifying bacterial consortium. AB - This work illustrates the co-composting of gelatin industry sludge (GIS) combined with organic fraction of municipal solid waste (OFMSW) and poultry waste (PW) employing 10% zeolite mixed with enriched nitrifying bacteria consortium (ENBC). Five piles of GIS were prepared mixed with OFMSW and PW at 2:1:0.5, 4:1:0.5, 6:1:0.5 and 8:1:0.5 and without GIS 0:1:0.5 (dry weight basis) served as control, while 10% zeolite mixed with ENBC was inoculated in all piles and composted for 42days. The Pile-4 with GIS, OFMSW and PW ratio 6:1:0.5 and 10% zeolite+ENBC were drastically reduced the nitrogen loss and enhance the mineralization rate as compare to other piles. The co-amendment of 6% GIS effectively buffered the pH between ~7.5 to 8.0 and shortened the compost maturity period, while lower concentration of GIS was comparatively delayed the early decomposition. Therefore, our results suggested that suitability of 10% zeolite+ENBC with initial feedstock ratio 6:1:0.5 as the best formulation for the composting of GIS into value-added stable product. PMID- 26897475 TI - A simple, repeated rTMS protocol effectively removes auditory verbal hallucinations in a single patient study. PMID- 26897476 TI - Elevated maternal cytokine levels at birth and risk for psychosis in adult offspring. AB - BACKGROUND: Pregnancy and birth complications, particularly those associated with maternal inflammation and fetal hypoxia, are associated with increased risk for schizophrenia later in life. However, the molecular mechanisms underlying these associations are not fully delineated. This study sought to examine the effect of exposure to maternal inflammation on risk of developing psychosis in adulthood. Maternal serum levels of pro-inflammatory Th1 cytokines (IL-2, interferon gamma [IFN-gamma], IL-12) and Th17 cytokines (IL-1b, IL-6, IL-8, tumor necrosis factor alpha [TNF-alpha], granulocyte macrophage colony stimulating factor [gm-csf]) and anti-inflammatory Th2 cytokines (IL-4, IL-5, and IL-13) and Treg cytokines (IL 10) were evaluated for association with later psychosis in the offspring. METHODS: Subjects were 43 adults with psychoses and 43 matched controls followed from gestation as part of the Philadelphia cohort of the National Collaborative Perinatal Project. Adult symptoms of psychosis were assessed via medical records review and confirmed with a validation study. Archived maternal serum samples collected at the time of birth were analyzed for cytokine levels using a multiplex bead assay. RESULTS: Individuals exposed to elevated maternal levels of anti-inflammatory Th2 cytokines (>=75th percentile) were significantly less likely to develop psychosis in adulthood. CONCLUSIONS: These results may suggest that increased maternal levels of anti-inflammatory cytokines during the perinatal period could protect against the development of psychosis. PMID- 26897477 TI - Ecological interface design and system safety: One facet of Rasmussen's legacy. AB - The focus of this manuscript is on cognitive systems engineering/ecological interface design (CSE/EID) and the role that this framework may play in improving system safety. First, the decision making and problem solving literatures are reviewed with an eye towards informational needs that are required to support these activities. The utility of two of Rasmussen's analytical tools (i.e., the abstraction and aggregation hierarchies) in conducting work domain analyses to identify associated information (i.e., categories and relationships) is discussed. The importance of designing ecological displays and interfaces that span the informational categories in the abstraction hierarchy is described and concrete examples are provided. The potential role that ecological interfaces can play in providing effective decision making (i.e., preventing accidents) and problem solving (i.e., dealing with accidents) support, thereby improving the safety of our socio-technical systems, is explored. PMID- 26897478 TI - Rasmussen's legacy in the great outdoors: A new incident reporting and learning system for led outdoor activities. AB - Jens Rasmussen's seminal risk management framework and accompanying Accimap method have become highly popular in safety science circles. Despite this, widespread adoption of the model and method in practice has not yet been achieved. This paper describes a project involving the development and implementation of an incident reporting and learning system underpinned by Rasmussen's risk management framework and Accimap method. The system was developed for the led outdoor activity sector in Australia to enable reporting and analysis of injuries and near miss incidents, with the aim of supporting the development of more effective countermeasures. An analysis of the data derived from the first 3 months use of the system by 43 organisations is presented. The outputs provide an in-depth Accimap-based analysis of all incidents reported by participating organisations over the 3 month period. In closing, the importance of developing usable domain specific tools to support translation of Ergonomics theory and methods in practice is discussed. PMID- 26897479 TI - Reliability and failure behavior of CAD-on fixed partial dentures. AB - OBJECTIVES: To estimate the reliability and failure behavior of fixed partial dentures (FPDs) fabricated using the CAD-on technique. METHODS: FPDs (n=25) were fabricated using a CAD/CAM system: IPS e.max ZirCAD - Crystall./Connect and IPS e.max CAD (Ivoclar). The restoration type ("three-unit bridge") and design method ("multilayer") based on Biogenerics were used. Framework and porcelain structures were united using a fusion ceramic (Crystall./Connect, Ivoclar). Mechanical fatigue was tested in a servohydraulic load frame machine at a cyclic loading (frequency: 2Hz; load ratio: 0.1). Based on previous data from specimens tested in fast fracture, three different stress profiles were used. The lifetime data were analyzed using an inverse power law-Weibull cumulative damage model (ALTA PRO, Reliasoft). All failed specimens were examined under a field emission scanning electron microscope. RESULTS: Porcelain chipping was the predominant (60%) mode of failure for FPDs tested in fast fracture and connector failure was predominant (67%) under fatigue. For fast fracture data, the Weibull modulus (beta) of FPDs was 7.8 combining the two failure modes. When chipping and connector fracture data were analyzed separately, beta values were 7.9 and 2.9. For the step stress fatigue test, beta values were lower than estimated using fast fracture, being 1.6 for connector fracture and 1.3 for porcelain chipping. SIGNIFICANCE: The test method (fast fracture or fatigue) significantly influenced the reliability of FPDs fabricated using the CAD-on technique, but it did not influence their failure behavior. PMID- 26897480 TI - Optimal Timing to Surgery after Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer. AB - BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) has demonstrated proven benefit in tumor regression and improved long-term local control for patients with locally advanced rectal cancer. However, precise analysis of the optimal waiting time that maximizes oncologic benefits of nCRT has not been established. STUDY DESIGN: The 2006-2012 National Cancer Data Base was queried for patients with stage II and III rectal adenocarcinoma who underwent nCRT followed by surgical resection. Time to surgery was defined as the difference between last date of radiotherapy and date of surgery. Primary study endpoints included resection margin positivity and pathologic downstaging. Multivariable regression modeling with restricted cubic splines was used to evaluate the adjusted association between time to surgery and our study endpoints, and to establish an optimal time threshold for surgery. RESULTS: A total of 11,760 patients were included. Median time to surgery was 53 days (interquartile range [IQR] 43 to 63 days). After adjusting for patient demographic, clinical, tumor, and treatment characteristics, our model determined an inflection point at 56 days after end of radiotherapy associated with the highest likelihood of complete resection and pathologic downstaging. With adjustment, the risk of margin positivity was increased in those who underwent surgery after 56 days from end of radiotherapy (odds ratio [OR] 1.40, 95% CI 1.21 to 1.61, p < 0.001). The likelihood of downstaging was increasing up to 56 days after radiotherapy (>=56 days vs <56 days, OR 1.2, 95% CI 1.02 to 1.23, p = 0.01). CONCLUSIONS: This study objectively determined the optimal time for surgery after completion of nCRT for rectal cancer based on completeness of resection and tumor downstaging. Eight weeks appears to be the critical threshold for optimal tumor response. PMID- 26897481 TI - Data mining framework for identification of myocardial infarction stages in ultrasound: A hybrid feature extraction paradigm (PART 2). AB - Early expansion of infarcted zone after Acute Myocardial Infarction (AMI) has serious short and long-term consequences and contributes to increased mortality. Thus, identification of moderate and severe phases of AMI before leading to other catastrophic post-MI medical condition is most important for aggressive treatment and management. Advanced image processing techniques together with robust classifier using two-dimensional (2D) echocardiograms may aid for automated classification of the extent of infarcted myocardium. Therefore, this paper proposes novel algorithms namely Curvelet Transform (CT) and Local Configuration Pattern (LCP) for an automated detection of normal, moderately infarcted and severely infarcted myocardium using 2D echocardiograms. The methodology extracts the LCP features from CT coefficients of echocardiograms. The obtained features are subjected to Marginal Fisher Analysis (MFA) dimensionality reduction technique followed by fuzzy entropy based ranking method. Different classifiers are used to differentiate ranked features into three classes normal, moderate and severely infarcted based on the extent of damage to myocardium. The developed algorithm has achieved an accuracy of 98.99%, sensitivity of 98.48% and specificity of 100% for Support Vector Machine (SVM) classifier using only six features. Furthermore, we have developed an integrated index called Myocardial Infarction Risk Index (MIRI) to detect the normal, moderately and severely infarcted myocardium using a single number. The proposed system may aid the clinicians in faster identification and quantification of the extent of infarcted myocardium using 2D echocardiogram. This system may also aid in identifying the person at risk of developing heart failure based on the extent of infarcted myocardium. PMID- 26897482 TI - Fight-or-flight Response in the ancient Egyptian novel "Sinuhe" (c. 1800 BCE). PMID- 26897483 TI - Reply - Letter to the Editor - Associations between tongue strength and swallowing difficulty in older adults receiving long-term care. PMID- 26897484 TI - Early administration of Enalapril prevents diastolic dysfunction and ventricular remodeling in rabbits with myocardial infarction. AB - We aimed to investigate the role of early administration of Enalapril (Enal) on post-myocardial infarction (MI) ventricular remodeling and diastolic dysfunction in rabbits. White New Zealand rabbits that underwent coronary artery ligature or Sham were divided in three experimental groups: (1) Sham, (2) MI, and (3) MI+Enal. Enal was given by gavage at a dose of 10mg/kg/day starting at 3h after surgery for 35days. At the end of the protocol, we measured (1) mean arterial pressure, (2) left ventricular (LV)+dP/dtmax, (3) LV end-diastolic pressure (LVEDP) and isovolumic relaxation (Tau), (4) LV dimensions, (5) LV ejection and shortening fraction, (6) infarct size (Masson's trichrome-stained slices), (7) fibrosis in the infarct and remote zone (Picrosirius red-stained slices), and (8) myocyte cross-sectional area (MCSA) in WGA-stained section. Enal reduced the mean arterial pressure by 30% as compared with untreated animals and Sham (P<.05). MI reduced LV+dP/dtmax and LV-dP/dtmax (mmHg/s), increased LVEDP (mmHg), Tau (ms), and t50 (ms) values, suggesting a decrease in the relaxation rate. LV end diastolic dimension and LV end-systolic dimension (LVESD, mm) increased in untreated MI (P<.05 vs. Sham). In contrast, Enal markedly prevented post-MI diastolic dysfunction by significantly decrease LVEDP from 8.2+/-0.2 to 5.1+/ 0.3mmHg, Tau from 19.8+/-0.8 to 15.3+/-0.9ms, and t50 from 12.4+/-0.5 to 9.6+/ 0.8ms as well as reduced LVESD from 15+/-1.1 to 12+/-0.8mm (P<.05 MI vs. MI+Enal). Collagen concentration in the scar was unaffected, but chronic treatment with Enal prevented myocardial fibrosis and MCSA in the remote zone. In summary, chronic early administration of Enal to rabbits with experimental MI has a favorable effect on ventricular remodeling and diastolic function by reducing MCSA and fibrosis, without affecting the wound healing. PMID- 26897485 TI - Pathobiology of Ischemic Heart Disease: Past, Present and Future. AB - This review provides a perspective on knowledge of ischemic heart disease (IHD) obtained from the contemporary era of research which began in the 1960s and has continued to the present day. Important discoveries have been made by basic and translational scientists and clinicians. Pathologists have contributed significantly to insights obtained from experimental studies and clinicopathological studies in humans. The review also provides a perspective for future directions in research in IHD aimed at increasing basic knowledge and developing additional therapeutic options for patients with IHD. PMID- 26897487 TI - Is the Anterior Approach Safe? Early Complication Rate Associated With 5090 Consecutive Primary Total Hip Arthroplasty Procedures Performed Using the Anterior Approach. AB - BACKGROUND: Few publications have raised concern with the safety of the anterior approach (AA) to total hip arthroplasty (THA). The purpose of this study is to report the early complications with AA THA in a combined, multicenter patient population from three different institutions. METHODS: The study cohort consisted of 5090 consecutive primary procedures in 4473 patients who had undergone THA utilizing the anterior approach between August 2006 and July 2013. Surgeries were performed by five surgeons at three sites that maintain prospective databases. Preoperative, intraoperative, and postoperative data were recorded on all patients. Demographic data including age, gender, and BMI were queried, as well as all intraoperative and postoperative complications in the first 90 days. RESULTS: The 5090 patients had a mean body mass index of 27.5, and mean age of 63.6 years. The overall 90-day complication rate was 1.9%. There were 41 intraoperative femur fractures including 29 calcar fractures, 9 greater trochanter fractures and 3 femoral shaft fractures. There were 7 postoperative femur fractures including 3 greater trochanter fractures, 2 calcar fractures, and 2 femur fractures. Other complications included 15 superficial infections, 5 deep infections, 12 dislocations, 8 hematomas, 3 cases of cellulitis, 2 sciatic nerve palsies, 1 peroneal nerve palsy, and intrapelvic bleed. The nonsurgical complication rate was 1.4%. Deep vein thrombosis occurred in 0.3% of cases. CONCLUSION: This large multicenter study of consecutive AA THAs demonstrates an acceptable risk profile within the first 90 days after surgery. PMID- 26897488 TI - Assessment of Damage on a Dual Mobility Acetabular System. AB - BACKGROUND: Dual mobility designs were introduced to increase stability and reduce the risk of dislocation, both being common reasons for surgical revision after total hip arthroplasty. The in vivo behavior of dual mobility constructs remains unclear, and to our knowledge, no data have been published describing in vivo surface damage to the polyethylene bearing surfaces. METHODS: We used surface damage assessed on the inner and outer polyethylene bearing surfaces in 33 short-term retrieved dual mobility liners as evidence of relative motion at the 2 bearings. A lever out test was performed to determine the force required for dislocation of the cobalt-chromium femoral head from the polyethylene liner. RESULTS: Both bearings showed damage; however, the inner polyethylene bearings had higher damage scores, lower prevalence of remaining machining marks, and higher incidence of concentric wear, all consistent with more motion at the inner polyethylene bearing. The inner polyethylene bearings also had a higher occurrence of embedded titanium debris. The damage sustained in vivo was insufficient to lead to intraprosthetic dislocation in any of the retrieved components. Lever out tests of 12 retrievals had a mean dislocation load of 261 +/- 52 N, which was unrelated to the length of implantation. CONCLUSION: Our short-term retrieval data of 33 highly cross-linked polyethylene dual mobility components suggest that although motion occurs at both bearing articulations, the motion of the femoral head against the inner polyethylene bearing dominates. Although damage was not severe enough to lead to intraprosthetic dislocation, failure may occur long term and should be assessed in future studies. PMID- 26897486 TI - Genome-wide association mapping of partial resistance to Aphanomyces euteiches in pea. AB - BACKGROUND: Genome-wide association (GWA) mapping has recently emerged as a valuable approach for refining the genetic basis of polygenic resistance to plant diseases, which are increasingly used in integrated strategies for durable crop protection. Aphanomyces euteiches is a soil-borne pathogen of pea and other legumes worldwide, which causes yield-damaging root rot. Linkage mapping studies reported quantitative trait loci (QTL) controlling resistance to A. euteiches in pea. However the confidence intervals (CIs) of these QTL remained large and were often linked to undesirable alleles, which limited their application in breeding. The aim of this study was to use a GWA approach to validate and refine CIs of the previously reported Aphanomyces resistance QTL, as well as identify new resistance loci. METHODS: A pea-Aphanomyces collection of 175 pea lines, enriched in germplasm derived from previously studied resistant sources, was evaluated for resistance to A. euteiches in field infested nurseries in nine environments and with two strains in climatic chambers. The collection was genotyped using 13,204 SNPs from the recently developed GenoPea Infinium(r) BeadChip. RESULTS: GWA analysis detected a total of 52 QTL of small size-intervals associated with resistance to A. euteiches, using the recently developed Multi-Locus Mixed Model. The analysis validated six of the seven previously reported main Aphanomyces resistance QTL and detected novel resistance loci. It also provided marker haplotypes at 14 consistent QTL regions associated with increased resistance and highlighted accumulation of favourable haplotypes in the most resistant lines. Previous linkages between resistance alleles and undesired late-flowering alleles for dry pea breeding were mostly confirmed, but the linkage between loci controlling resistance and coloured flowers was broken due to the high resolution of the analysis. A high proportion of the putative candidate genes underlying resistance loci encoded stress-related proteins and others suggested that the QTL are involved in diverse functions. CONCLUSION: This study provides valuable markers, marker haplotypes and germplasm lines to increase levels of partial resistance to A. euteiches in pea breeding. PMID- 26897489 TI - An Algorithmic, Pie-Crusting Medial Soft Tissue Release Reduces the Need for Constrained Inserts Patients With Severe Varus Deformity Undergoing Total Knee Arthroplasty. AB - BACKGROUND: We studied the need to use a constrained insert for residual intraoperative instability and the 1-year result of patients undergoing total knee arthroplasty (TKA) for a varus deformity. In a control group, a "classic" subperiosteal release of the medial soft tissue sleeve was performed as popularized by pioneers of TKA. In the study group, an algorithmic approach that selectively releases and pie-crusts posteromedial structures in extension and anteromedial structures in flexion was used. METHODS: All surgeries were performed by a single surgeon using measured resection technique, and posterior stabilized, cemented implants. There were 228 TKAs in the control group and 188 in the study group. Outcome variables included the use of a constrained insert, and the Knee Society Score at 6 weeks, 4 months, and 1 year postoperatively. The effect of the release technique on use of constrained inserts and clinical outcomes were analyzed in a multivariate model controlling for age, sex, body mass index, and severity of deformity. RESULTS: The use of constrained inserts was significantly lower in study than in control patients (8% vs 18%; P = .002). There was no difference in the Knee Society Score and range of motion between the groups at last follow-up. No patient developed postoperative medial instability. CONCLUSION: This algorithmic, pie-crusting release technique resulted in a significant reduction in the use of constrained inserts with no detrimental effects in clinical results, joint function, and stability. As constrained TKA implants are more costly than nonconstrained ones, if the adopted technique proves to be safe in the long term, it may cause a positive shift in value for hospitals and cost savings in the health care system. PMID- 26897490 TI - Is There a Benefit for Liposomal Bupivacaine Compared to a Traditional Periarticular Injection in Total Knee Arthroplasty Patients With a History of Chronic Opioid Use? AB - BACKGROUND: Postoperative pain after total knee arthroplasty (TKA) poses a major challenge. It delays mobilization, increases opioid consumption and side effects, and lengthens hospitalization. This challenge multiplies when treating an opioid dependent population. We examined whether a novel suspended release local anesthetic, liposomal bupivacaine (LB) would improve pain control and decrease opioid consumption after TKA compared to a standard periarticular injection in opioid-dependent patients. METHODS: Thirty-eight patients undergoing TKA were randomly assigned to receive either a periarticular injection (PAI) with LB (n = 20) or with a standard PAI (including a combination of ropivacaine, clonidine, Toradol, Epinepherine, and saline; n = 18) as part of a multimodal pain management approach. All periarticular injections were done by a single surgeon. Perioperative treatment was similar between groups. Postoperative information regarding pain level was evaluated by a pain visual analog scale score. Postoperative opioid consumption was recorded. RESULTS: After controlling baseline narcotic usage before surgery, no differences were found between groups in daily postoperative narcotic usage (P = .113), average daily pain score (P = .332), or maximum daily pain score (P = .881). However, when examining pain levels separately for each day, pain visual analog scale scores were reported higher in post operative day 1 in the LB group (P = .033). CONCLUSIONS: LB was not found to be superior to standard PAI in opioid-dependent patients undergoing TKA. This patient population continues to present a challenge even with modern multimodal pain protocols. PMID- 26897491 TI - Trends and Outcomes in the Treatment of Failed Septic Total Knee Arthroplasty: Comparing Arthrodesis and Above-Knee Amputation. AB - BACKGROUND: Options for treatment of a failed septic total knee arthroplasty (TKA) include arthrodesis and above-knee amputation (AKA). Little comparative data exist to help clinicians when considering these alternatives. METHODS: A national database was queried for patients who underwent either knee arthrodesis or AKA for an infected TKA between 2005 and 2012. Procedure volumes, postoperative complications, hospital charges, length of stay, and 90-day readmission rates were evaluated. RESULTS: A total of 2634 patients underwent arthrodesis and 5001 patients underwent AKA for septic TKA. The percentage of total patients who underwent AKA increased significantly throughout the study period compared to knee arthrodesis. Patients who underwent AKA tended to be older and have more medical comorbidities. Arthrodesis patients had a significantly higher rate of postoperative infection (14.5% vs 8.3%, P < .0001) and transfusion (55.1% vs 46.8%, P < .0001), whereas AKA patients had a higher rate of systemic complications (31.5% vs 25.9%, P < .0001) and in-hospital mortality (3.7% vs 2.1%, P < .0001). The AKA cohort had lower hospital charges ($79,686 vs $84,747, P = .004), longer length of stay (11 vs 7 days, P < .0001), and higher 90-day readmission rate (19.4% vs 16.9%). CONCLUSION: Our data suggest that there is an increasing trend toward AKA for the treatment of a failed infected TKA when compared to arthrodesis. Comparative analysis of the outcomes of these procedures should help the clinician when weighing these alternatives. PMID- 26897492 TI - The Transverse Acetabular Ligament as an Intraoperative Guide to Cup Abduction. AB - BACKGROUND: The success of a total hip arthroplasty relies on optimal acetabular cup placement to ensure mating of the femoral head and acetabular cup throughout all positions of the hip joint. Poor cup placement is associated with dislocation, impingement, microseparation, component loosening, and accelerated wear due to rim loading. This study examined a novel method of using the transverse acetabular ligament (TAL) to guide cup inclination during primary total hip arthroplasty. METHODS: A descriptive study using 16 hips from 9 cadavers. A computer navigation system measured inclination and version of the acetabular component in 3 positions with the lower edge of cup: (1) flush with, (2) 5 mm proximal to, and (3) 5 mm distal to free border of the TAL. RESULTS: The median inclination angles were 44 degrees in position (1), 30 degrees in position (2), and 64 degrees in position (3). The median anteversion angle for all positions was 19 degrees . CONCLUSION: Cup inclination was acceptable when the lower edge of the cup was flush or within 5 mm proximal to the TAL. PMID- 26897493 TI - Patient Attitudes Toward Orthopedic Surgeon Ownership of Related Ancillary Businesses. AB - BACKGROUND: Physician ownership of businesses related to orthopedic surgery, such as surgery centers, has been criticized as potentially leading to misuse of health care resources. The purpose of this study was to determine patients' attitudes toward surgeon ownership of orthopedic-related businesses. METHODS: We surveyed 280 consecutive patients at 2 centers regarding their attitudes toward surgeon ownership of orthopedic-related businesses using an anonymous questionnaire. Three surgeon ownership scenarios were presented: (1) owning a surgery center, (2) physical therapy (PT), and (3) imaging facilities (eg, Magnetic Resonance Imaging scanner). RESULTS: Two hundred fourteen patients (76%) completed the questionnaire. The majority agreed that it is ethical for a surgeon to own a surgery center (73%), PT practice (77%), or imaging facility (77%). Most (>67%) indicated that their surgeon owning such a business would have no effect on the trust they have in their surgeon. Although >70% agreed that a surgeon in all 3 scenarios would make the same treatment decisions, many agreed that such surgeons might perform more surgery (47%), refer more patients to PT (61%), or order more imaging (58%). Patients favored surgeon autonomy, however, believing that surgeons should be allowed to own such businesses (78%). Eighty-five percent agreed that patients should be informed if their surgeon owns an orthopedic related business. CONCLUSION: Although patients express concern over and desire disclosure of surgeon ownership of orthopedic-related businesses, the majority believes that it is an ethical practice and feel comfortable receiving care at such a facility. PMID- 26897494 TI - Qualitative analysis of bibliotherapy as a tool for adults who stutter and graduate students. AB - PURPOSE: The purpose of this study was to investigate the use of bibliotherapy as a therapeutic tool for adults who stutter (AWS) and as an educational tool for graduate students in speech-language pathology. Bibliotherapy refers to the process of reading, reflecting upon, and discussing literature, often first person illness or disability narratives, to promote cognitive shifts in the way clients and clinicians conceptualize the experience of disability. METHOD: Five AWS and six graduate students participated in supervised bibliotherapy using a stuttering memoir during therapy sessions. An inductive, qualitative analysis was utilized to analyze data collected from questionnaires and interviews. An additional deductive qualitative approach was utilized to explore how client data fit into an existing five-outcome model of bibliotherapy from the psychology literature. RESULTS: Graduate students reported developing essential clinical skills for working with clients who stutter, including an improved understanding of the experience of people who stutter and an increased ability to form and strengthen the therapeutic alliance. Clients reported experiencing shifts in the cognitive and affective components of the disorder. Imposing the five-outcome model on client data indicates that at least two clients in the current study experienced all five outcomes of bibliotherapy. These include client experiences of involvement, identification, catharsis, insight and universalism. CONCLUSION: Both graduate students and clients reported benefits from reading and discussing a memoir about stuttering. Bibliotherapy can be an effective tool in therapy and clinical education when used appropriately. PMID- 26897495 TI - Parent verbal contingencies during the Lidcombe Program: Observations and statistical modeling of the treatment process. AB - PURPOSE: The purpose of this study was to document parent presentation of the Lidcombe Program verbal contingencies and model potential relationships between contingency provision and treatment duration. METHODS: Forty parent-child pairs undertaking the Lidcombe Program participated, 26 of whom completed Stage 1. All participants were included in the analyses. Parents completed weekly audio recordings of treatment during practice sessions and a diary of treatment during natural conversations. The number and types of contingencies provided during practice sessions were counted for 520 recordings. Accelerated failure time modeling was used to investigate associations between contingency provision during the first 4 weeks of treatment and duration of time to complete Stage 1. RESULTS: During practice sessions 91% of contingencies were for stutter-free speech, 6.8% were for stuttering and 2.7% were incorrectly applied. Parents often combined several verbal contingencies into one. During natural conversations, the number of verbal contingencies reportedly provided across the day was low, an average of 8.5 (SD=7.82) contingencies for stutter-free speech and 1.7 (SD=2.43) for unambiguous stuttering. There was a positive, significant relationship between the number of verbal contingencies for stuttering provided during the first 4 weeks of treatment and time taken to complete Stage 1. CONCLUSION: Parents mostly provided the expected types of contingencies but the number was lower than expected. An unexpected association was found between number of verbal contingencies for stuttering and treatment duration. Further research is required to explore the relation between rates of parent verbal contingencies, treatment process duration, and treatment outcome. PMID- 26897496 TI - Associations between beliefs about and reactions toward people who stutter. AB - PURPOSE: This study sought to assess whether beliefs about people who stutter (PWS) predict intended behavioral and affective reactions toward them in a large and varied sample of respondents while taking into account familiarity with PWS and the demographic variables of age, education, and gender. METHODS: Analyses were based on 2206 residents of the United States of America. The seemingly unrelated regression (SUR) technique was used to test the relationship between beliefs about PWS and behavioral and affective reactions toward PWS. Variables such as familiarity with PWS and demographic data were also controlled in the statistical model. RESULTS: Findings indicated that, when demographic variables and familiarity were taken into account, the accuracy of participants' beliefs about PWS significantly predicted their intended behavioral and affective reactions toward PWS. The participants' gender and familiarity with PWS were also associated with these reactions toward PWS. CONCLUSION: The finding of an association between beliefs and intended reactions validates attempts to improve public treatment of PWS through improving the accuracy of beliefs about PWS. Additionally, because familiarity with PWS is a significant predictor of helpful and positive reactions toward PWS, interventions involving PWS educating others through direct interpersonal interactions may be one effective way to improve public reactions toward individuals who stutter. PMID- 26897497 TI - Speech pathology student clinician attitudes and beliefs towards people who stutter: A mixed-method pilot study. AB - PURPOSE: Stuttering is a disorder of fluency that extends beyond its physical nature and has social, emotional and vocational impacts. Research shows that individuals often exhibit negative attitudes towards people who stutter; however, there is limited research on the attitudes and beliefs of speech pathology students towards people who stutter in Australia. Existing research is predominantly quantitative; whereas this mixed-method study placed an emphasis on the qualitative component. The purpose of this study was to explore the attitudes and beliefs of final year Australian speech pathology students towards people who stutter. METHODS: This mixed-method study applied the Public Opinion Survey of Human Attributes - Stuttering (POSHA-S) and semi-structured interviews to gather data from final year speech pathology students from a major university in Australia. PRINCIPAL RESULTS: The overall qualitative findings identified that final year Australian speech pathology students exhibit positive attitudes towards people who stutter. The results also illustrated the role of education in influencing attitudes of students as well as increasing their confidence to work with people who stutter. MAJOR CONCLUSION: This research revealed that Australian final year speech pathology students exhibit positive attitudes towards people who stutter. They displayed an understanding that people who stutter may have acquired traits such as shyness as a response to their personal situation and environment, rather than those traits being endemic to them. Results also suggested that education can play a role in creating confident student clinicians in their transition to practice, and positively influence their attitudes and beliefs. PMID- 26897498 TI - Feto-maternal outcomes of pregnancy complicated by Krukenberg tumor: a systematic review of literature. AB - PURPOSE: Krukenberg tumor is a rare type of ovarian cancer with a poor prognosis, and little is known about its behavior during pregnancy. METHODS: A systematic review was conducted to identify pregnancies complicated by Krukenberg tumor, correlated to oncologic and neonatal outcomes (n = 35). RESULTS: Mean age of cases was 30.4 years, and the most common origin of primary cancer was the stomach (68.6 %) followed by the colon (14.3 %). The two most common presenting symptoms were abdominal/pelvic pain (51.4 %) and nausea/vomiting (48.6 %). Two thirds of tumors were bilateral (65.7 %) and the average size was 16.7 cm. Ascites (45.7 %), carcinomatosis (25.7 %) and non-ovarian distant metastases (14.3 %) were found at the time of surgery. Chemotherapy was administered in 20 cases, with fetal exposure in two of these. The ovarian tumor was identified prior to the primary cancer diagnosis in all 28 cases. The overall number of live births was 27 (81.8 %). The median survival was 6 months after Krukenberg tumor diagnosis. In univariate analysis, decreased overall survival was associated with dyspnea, ascites, carcinomatosis, non-radical surgery for the primary cancer, and residual disease at surgery (all, p < 0.05). On multivariate analysis, dyspnea and carcinomatosis remained independent prognostic factors for decreased overall survival after Krukenberg tumor diagnosis (2-year overall survival rates, dyspnea 0 vs. 56.6 %, adjusted-hazard ratio [HR] 9.74, 95 % confidence interval [CI] 2.04 46.2, p < 0.01; and carcinomatosis, 0 vs. 58.1 %, adjusted-HR 7.95, 95 % CI 1.76 36.0, p < 0.01). CONCLUSIONS: Our results showed that prognosis of Krukenberg tumor complicated pregnancies is extremely poor, however it may be improved if radical surgery is achievable. PMID- 26897500 TI - Reviewing the connection between speech and obstructive sleep apnea. AB - BACKGROUND: Sleep apnea (OSA) is a common sleep disorder characterized by recurring breathing pauses during sleep caused by a blockage of the upper airway (UA). The altered UA structure or function in OSA speakers has led to hypothesize the automatic analysis of speech for OSA assessment. In this paper we critically review several approaches using speech analysis and machine learning techniques for OSA detection, and discuss the limitations that can arise when using machine learning techniques for diagnostic applications. METHODS: A large speech database including 426 male Spanish speakers suspected to suffer OSA and derived to a sleep disorders unit was used to study the clinical validity of several proposals using machine learning techniques to predict the apnea-hypopnea index (AHI) or classify individuals according to their OSA severity. AHI describes the severity of patients' condition. We first evaluate AHI prediction using state-of-the-art speaker recognition technologies: speech spectral information is modelled using supervectors or i-vectors techniques, and AHI is predicted through support vector regression (SVR). Using the same database we then critically review several OSA classification approaches previously proposed. The influence and possible interference of other clinical variables or characteristics available for our OSA population: age, height, weight, body mass index, and cervical perimeter, are also studied. RESULTS: The poor results obtained when estimating AHI using supervectors or i-vectors followed by SVR contrast with the positive results reported by previous research. This fact prompted us to a careful review of these approaches, also testing some reported results over our database. Several methodological limitations and deficiencies were detected that may have led to overoptimistic results. CONCLUSION: The methodological deficiencies observed after critically reviewing previous research can be relevant examples of potential pitfalls when using machine learning techniques for diagnostic applications. We have found two common limitations that can explain the likelihood of false discovery in previous research: (1) the use of prediction models derived from sources, such as speech, which are also correlated with other patient characteristics (age, height, sex,...) that act as confounding factors; and (2) overfitting of feature selection and validation methods when working with a high number of variables compared to the number of cases. We hope this study could not only be a useful example of relevant issues when using machine learning for medical diagnosis, but it will also help in guiding further research on the connection between speech and OSA. PMID- 26897499 TI - Older patients with low Charlson score and high-risk prostate cancer benefit from radical prostatectomy. AB - INTRODUCTION: The aim of the study was to identify the appropriate level of Charlson comorbidity index (CCI) in older patients (>70 years) with high-risk prostate cancer (PCa) to achieve survival benefit following radical prostatectomy (RP). METHODS: We retrospectively analyzed 1008 older patients (>70 years) who underwent RP with pelvic lymph node dissection for high-risk prostate cancer (preoperative prostate-specific antigen >20 ng/mL or clinical stage >=T2c or Gleason >=8) from 14 tertiary institutions between 1988 and 2014. The study population was further grouped into CCI < 2 and >=2 for analysis. Survival rate for each group was estimated with Kaplan-Meier method and competitive risk Fine Gray regression to estimate the best explanatory multivariable model. Area under the curve (AUC) and Akaike information criterion were used to identify ideal 'Cut off' for CCI. RESULTS: The clinical and cancer characteristics were similar between the two groups. Comparison of the survival analysis using the Kaplan Meier curve between two groups for non-cancer death and survival estimations for 5 and 10 years shows significant worst outcomes for patients with CCI >= 2. In multivariate model to decide the appropriate CCI cut-off point, we found CCI 2 has better AUC and p value in log rank test. CONCLUSION: Older patients with fewer comorbidities harboring high-risk PCa appears to benefit from RP. Sicker patients are more likely to die due to non-prostate cancer-related causes and are less likely to benefit from RP. PMID- 26897501 TI - [Glycemic changes during menstrual cycles in women with type 1 diabetes]. AB - BACKGROUND AND OBJECTIVE: To determine frequency of women with type 1 diabetes showing menstrual cyclic changes in glycemia, analyze their clinical characteristics, and assess the pattern of glycemic changes. PATIENTS AND METHODS: We analyzed glucose meter readings along 168 menstrual cycles of 26 women with type 1 diabetes. We evaluated mean glucose, mean glucose standard deviation, mean fasting glucose, percentage of glucose readings>7.8 mmol/L and<3.1 mmol/L, and mean insulin dose in 4 periods for each cycle. A woman was identified as having cyclic changes when mean glucose rose from early follicular to late luteal in two-thirds of her menstrual cycles. RESULTS: A percentage of 65.4 of the women had cyclic changes. Characteristics of women with and without cyclic changes, including self-perception of glycemic changes, were similar with exception of age at diabetes diagnosis (22.5 [7.5] vs. 14.4 [9.5] years; P=.039). In women with cyclic changes mean percentage of glucose readings>7.8 mmol/L rose from early follicular (52.2 [16.3] %) to early and late luteal (58.4 [16.0] %, P=.0269; 61.0 [16.9] %, P=.000). CONCLUSION: Almost two-thirds of women with type 1 diabetes experience a menstrual cycle phenomenon, attributable to an increase in hyperglycemic excursions during the luteal phase. Enabling women to evaluate their weekly mean glucose from their meter and exploring the causes of hyperglycemic excursions during luteal phase should ensure more accuracy when giving instructions for diabetes management in women with premenstrual hyperglycemia. PMID- 26897502 TI - [Practical use of pneumococcal antigen assessment in urine]. PMID- 26897503 TI - [Intraabdominal fat redistribution in long-term continuous positive airway pressure treatment in obstructive sleep apnea patients]. AB - BACKGROUND AND OBJECTIVE: Obesity is the main risk factor for obstructive sleep apnoea (OSA). The aim was to evaluate the long-term effect of continuous positive airway pressure (CPAP) on intraabdominal fat distribution in OSA patients. PATIENTS AND METHODS: Fifty OSA patients with and 35 without CPAP treatment criteria were followed-up for 2 years. Visceral and subcutaneous adipose tissue (VAT and SAT) and preaortic intraabdominal fat (PIF) were assessed by sonography. RESULTS: In the non CPAP treated group, SAT and VAT mean values didn't change, while a significantly PIF growth was observed (55.19 [23.44] vs. 63.45 [23.94] mm, P=.021). In the CPAP treated group, VAT and PIF mean were not changed, while SAT decreased significantly (11.29 [5.69] vs. 10.47 [5.71] mm, P=.012). CONCLUSIONS: Long-term CPAP treatment produces intraabdominal fat redistribution and is associated with an anthropometric profile of lower cardiovascular risk in OSA patients. PMID- 26897505 TI - [Rhino-orbital mucormycosis]. PMID- 26897504 TI - [Benefits of an educational intervention on diet and anthropometric profile of women with one cardiovascular risk factor]. AB - BACKGROUND AND OBJECTIVE: To assess whether an educational intervention in perimenopausal women with hypertension, diabetes mellitus and/or dyslipidaemia would improve adherence to a Mediterranean diet pattern and achieve changes in anthropometric parameters. PATIENTS: Randomized clinical trial of parallel groups: 320 women (45-60 years) in 2 urban primary care services. VARIABLES STUDIED: hip and waist circumference, body mass index (BMI), total, visceral and trunk fat (bioimpedance measures) and adherence to Mediterranean diet (MEDAS-14 questionnaire). Intervention group: 3 interactive workshops on prevention of cardiovascular disease, and control group: information by post. RESULTS: Two hundred and thirty women completed the study (113 control group and 117 intervention group). The differences between groups were significant in all parameters one year later. In the intragroup comparison, the intervention group maintained their BMI and improved adherence to the Mediterranean diet. The control group increased their BMI, abdominal and hip circumference and fat parameters (total, visceral and trunk fat). CONCLUSIONS: A simple educational intervention in perimenopausal women with cardiovascular risk can improve their healthy habits. PMID- 26897506 TI - [Janeway lesions, Osler nodes and splinter hemorrhages]. PMID- 26897507 TI - [Pulmonary complications of malaria: An update]. AB - Malaria is the most important parasitic disease worldwide, being a public health challenge in more than 90 countries. The incidence of pulmonary manifestations has increased in recent years. Acute respiratory distress syndrome is the most severe form within the pulmonary complications of malaria, with high mortality despite proper management. This syndrome manifests with sudden dyspnoea, cough and refractory hypoxaemia. Patients should be admitted to intensive care units and treated with parenteral antimalarial drug treatment and ventilatory and haemodynamic support without delay. Therefore, dyspnoea in patients with malaria should alert clinicians, as the development of respiratory distress is a poor prognostic factor. PMID- 26897508 TI - [Pulmonary arterial hypertension associated with human immunodeficiency virus infection: study of 4 cases]. AB - BACKGROUND AND OBJECTIVE: Pulmonary arterial hypertension (PAH) is a rare and progressive disease that can be inherited as autosomal dominant form. The BMPR2, ACVRL1 and ENG genes are main genes involved in the pathology. PAH associated to human immunodeficiency virus (HIV) is another rare disease with a low incidence, prevalence and survival. The main objective of this analysis was to study the clinical and molecular characteristics of PAH associated to HIV patients. PATIENTS: We present 4 cases of HIV patients who developed PAH and have been treated with ambrisentan. RESULTS: Pathogenic mutations have been identify in analyzed genes in 3 of the four analyzed patients. In addition, these patients present other changes classified as benign after a thorough in silico analysis. We identified some changes in genetic modifiers that predispose to these patients to more severe phenotype. CONCLUSIONS: The clinical analysis can help to define monitoring for these patients and the administration of appropriate treatment. These patients also have shown several pathogenic mutations. PMID- 26897509 TI - [A patient with waxy plaques on the nose]. PMID- 26897510 TI - Emergency Contraception for Adolescents: A Political Battle. AB - The political debate for adolescents to have access to emergency contraception that is available over the counter has been going on for years. Since 1999, Levonorgestrel, Plan B One Step(r), has been used in the United States as an emergency contraception but with a prescription at the time. The FDA has done years of research and testing with Barr Laboratories, the manufacture of Plan B One Step(r), to make it safe for females of all ages. In 2003, the FDA recommended the over the counter use of Plan B One Step(r) for all ages, yet this did not occur. In pharmacies across our nation young women find it impossible to purchase this product whether they be of age or not. Politics is making the choices for our young females, not medical evidence. How long are we going to let this continue? PMID- 26897511 TI - Association of Polymorphisms in Intercellular Adhesion Molecule 1 (ICAM-1) Gene with Cancer Susceptibility: A Meta-Analysis of 14 Case-Control Studies. AB - BACKGROUND Many epidemiology studies have indicated that polymorphisms in ICAM-1 are associated with a variety of cancers, but published data are contradictory and inconclusive. Therefore, we conducted the current meta-analysis to elaborate the effects of ICAM-1 polymorphisms (rs5491, rs3093030, rs281432, and rs1799969) on cancer susceptibility. MATERIAL AND METHODS We conducted a comprehensive literature search in PubMed, Web of Science, and Google Scholar. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association between ICAM-1 polymorphisms and cancer susceptibility. RESULTS We enrolled 14 published case-control studies including 4608 cancer cases and 4913 controls. We found an increased susceptibility of cancer in polymorphism rs1799969 (C vs. T: OR=1.662, 95%CI=1.288-2.143, p=0141; CT vs. TT: OR=1.860, 95%CI=1.398-2.474, p=0.507; CC+CT vs. TT: OR=1.812, 95%CI=1.373-2.391, p=0.284) of ICAM-1 among the overall population. However, no association between polymorphisms rs5491, rs3093030, or rs281432 of ICAM-1 and cancer susceptibility was identified. In the stratification analysis by ethnicity, we identified an increased susceptibility for Asians in rs3093030 polymorphism (CC vs. TC+TT: OR=1.728, 95% CI=1.234-2.421, p=0.787). CONCLUSIONS Our results suggest that the ICAM-1 polymorphism rs1799969 is significantly associated with increased susceptibility to overall cancer. Further studies (preferably prospective) are warranted to validate these relationships. PMID- 26897512 TI - Multivariable model development and internal validation for prostate cancer specific survival and overall survival after whole-gland salvage Iodine-125 prostate brachytherapy. AB - BACKGROUND: Whole-gland salvage Iodine-125-brachytherapy is a potentially curative treatment strategy for localised prostate cancer (PCa) recurrences after radiotherapy. Prognostic factors influencing PCa-specific and overall survival (PCaSS & OS) are not known. The objective of this study was to develop a multivariable, internally validated prognostic model for survival after whole gland salvage I-125-brachytherapy. MATERIALS AND METHODS: Whole-gland salvage I 125-brachytherapy patients treated in the Netherlands from 1993-2010 were included. Eligible patients had a transrectal ultrasound-guided biopsy-confirmed localised recurrence after biochemical failure (clinical judgement, ASTRO or Phoenix-definition). Recurrences were assessed clinically and with CT and/or MRI. Metastases were excluded using CT/MRI and technetium-99m scintigraphy. Multivariable Cox-regression was used to assess the predictive value of clinical characteristics in relation to PCa-specific and overall mortality. PCa-specific mortality was defined as patients dying with distant metastases present. Missing data were handled using multiple imputation (20 imputed sets). Internal validation was performed and the C-statistic calculated. Calibration plots were created to visually assess the goodness-of-fit of the final model. Optimism corrected survival proportions were calculated. All analyses were performed according to the TRIPOD statement. RESULTS: Median total follow-up was 78months (range 5-139). A total of 62 patients were treated, of which 28 (45%) died from PCa after mean (+/-SD) 82 (+/-36) months. Overall, 36 patients (58%) patients died after mean 84 (+/-40) months. PSA doubling time (PSADT) remained a predictive factor for both types of mortality (PCa-specific and overall): corrected hazard ratio's (HR's) 0.92 (95% CI: 0.86-0.98, p=0.02) and 0.94 (95% CI: 0.90-0.99, p=0.01), respectively (C-statistics 0.71 and 0.69, respectively). Calibration was accurate up to 96month follow-up. Over 80% of patients can survive 8years if PSADT>24months (PCaSS) and >33months (OS). Only approximately 50% survival is achieved with a PSADT of 12months. CONCLUSION: A PSADT of respectively >24months and >33months can result in >80% probability of PCa- specific and overall survival 8years after whole-gland salvage I-125 brachytherapy. Survival should be weighed against toxicity from a salvage procedure. Larger series and external validation are necessary. PMID- 26897513 TI - Radiation therapy combined with hyperthermia versus cisplatin for locally advanced cervical cancer: Results of the randomized RADCHOC trial. AB - BACKGROUND: Chemoradiation (RT-CT) is standard treatment for locally advanced cervical cancer (LACC). This study tried to establish if radiotherapy combined with hyperthermia (RT-HT) should be preferred in bulky and/or FIGO-stage ?III. METHODS: In this open-label, multicenter randomized trial, patients with LACC were randomly assigned by a computer-generated, biased coin minimization technique to RT-CT or RT-HT. Central randomization was done with stratification by FIGO-stage, tumour diameter and nodal status. Primary endpoint was event free survival (EFS). Secondary endpoints were pelvic recurrence free survival (PRFS), overall survival (OS) and treatment related toxicity. Analysis was done by intention to treat. RESULTS: The trial was closed prematurely (87 of 376 planned patients enrolled: 43 RT-CT; 44 RT-HT). Median follow-up time was 7.1 years. The cumulative incidence of an event was 33% in the RT-CT group and 35% in the RT-HT group. The corresponding hazard rate (HR) for EFS was 1.15 (CI: 0.56-2.36, p=0.7). Also the hazards for PRFS (0.94; CI 0.36-2.44) and OS (1.04; CI 0.48 2.23) at 5 years were comparable between both treatment arms as was grade ?3 radiation related late toxicity (6 RT-CT and 5 RT-HT patients). CONCLUSION: After 25% of intended accrual, data suggest comparable outcome for RT-CT and RT-HT. PMID- 26897514 TI - Pattern of failure in 5001 patients treated for glottic squamous cell carcinoma with curative intent - A population based study from the DAHANCA group. AB - PURPOSE: To describe the pattern of failure in a national consecutive cohort of patients with glottic squamous cell carcinomas (SCC) treated with primary radiotherapy (RT) with curative intent over a 41-year period. MATERIALS AND METHODS: All patients undergoing curative treatment for a glottic SCC diagnosed in Denmark between 1971 and 2011 were included and followed from the first contact with the oncology center to death or February 15, 2015. RESULTS: 5001 patients were identified of whom 98% had primary RT. The median follow-up was 9.1 years/5.7 years (patients alive/patients who died). Ten patients were lost to follow-up. In total 1511 failures were observed; of these 93%, 11% and 5% included T site, N site, and M site, respectively. For patients diagnosed in the 70s and the 00s, respectively, the five-year incidences were: local failure (32% vs 19%), loco-regional failure (34% vs 21%), laryngectomy (26% vs 10%), laryngectomy-free survival (48% vs 62%), disease-free survival (62% vs 68%), and overall survival (62% vs 68%). The five-year incidence of ultimate failure (13 16%) remained statistically unchanged. CONCLUSION: From the 70s to the 00s a continually improving primary disease-control was observed with a concurrent decrease in the incidence of laryngectomy. The survival rate was significantly higher in the 00s compared to the previous three decades. PMID- 26897516 TI - Bridging the valley of death: The new Radiotherapy & Oncology section "First in man - Translational innovations in radiation oncology". PMID- 26897517 TI - Histopathology-derived modeling of prostate cancer tumor control probability: Implications for the dose to the tumor and the gland. AB - PURPOSE: To evaluate the impact of GTV-CTV dose differentiation by simulating response of prostate patients to radiotherapy, considering histopathology of prostatectomy specimens. MATERIAL AND METHODS: Tumors' cell numbers (N0) and Gleason Scores (GS) were derived from histopathology of 25 specimens. Index lesions and tumors ?0.5cm(3) were considered GTV. Satellites <0.5cm(3) constituted the tumor load in the CTV. Each patient's tumor control probability (TCP) was simulated using the linear quadratic model and considering the N0 while assuming either a constant or GS-dependent alpha and beta. RESULTS: 19/25 patients had multi-focal disease. In 11 patients the CTV contained GS 4+3 or 4+4 tumors. Compared to the GTV, the CTV pathology was more favorable. For an alpha=0.140Gy(-1), a GTV dose of 79Gy with a CTV dose of 72Gy achieved an 80% TCP in the population. Varying alpha between 0.160-0.118Gy(-1) with GS, a GTV and CTV dose of 80Gy and 70Gy also gave an 80% TCP. CONCLUSIONS: Considering only N0, our simulations suggest that a GTV-CTV dose differentiation of 7Gy would not compromise TCP of the patient population. When assuming an increased radiosensitivity with lower GS, a further dose differentiation of 10Gy might be feasible. PMID- 26897519 TI - Molecular dynamics simulations of a lithium/sodium carbonate mixture. AB - The diffusion and ionic conductivity of Li x Na1-x CO3 salt mixtures were studied by means of Molecular Dynamics (MD) simulations, using the Janssen and Tissen model (Janssen and Tissen, Mol Simul 5:83-98; 1990). These salts have received particular attention due to their central role in fuel cells technology, and reliable numerical methods that could perform as important interpretative tool of experimental data are thus required but still lacking. The chosen computational model nicely reproduces the main structural behaviour of the pure Li2CO3, Na2CO3 and K2CO3 carbonates, but also of their Li/K and Li/Na mixtures. However, it fails to accurately describe dynamic properties such as activation energies of diffusion and conduction processes, outlining the need to develop more accurate models for the simulation of molten salt carbonates. PMID- 26897515 TI - Beyond mean pharyngeal constrictor dose for beam path toxicity in non-target swallowing muscles: Dose-volume correlates of chronic radiation-associated dysphagia (RAD) after oropharyngeal intensity modulated radiotherapy. AB - PURPOSE/OBJECTIVE(S): We sought to identify swallowing muscle dose-response thresholds associated with chronic radiation-associated dysphagia (RAD) after IMRT for oropharyngeal cancer. MATERIALS/METHODS: T1-4 N0-3 M0 oropharyngeal cancer patients who received definitive IMRT and systemic therapy were examined. Chronic RAD was coded as any of the following ?12months post-IMRT: videofluoroscopy/endoscopy detected aspiration or stricture, gastrostomy tube and/or aspiration pneumonia. DICOM-RT plan data were autosegmented using a custom region-of-interest (ROI) library and included inferior, middle and superior constrictors (IPC, MPC, and SPC), medial and lateral pterygoids (MPM, LPM), anterior and posterior digastrics (ADM, PDM), intrinsic tongue muscles (ITM), mylo/geniohyoid complex (MHM), genioglossus (GGM), masseter (MM), buccinator (BM), palatoglossus (PGM), and cricopharyngeus (CPM), with ROI dose-volume histograms (DVHs) calculated. Recursive partitioning analysis (RPA) was used to identify dose-volume effects associated with chronic-RAD, for use in a multivariate (MV) model. RESULTS: Of 300 patients, 34 (11%) had chronic-RAD. RPA showed DVH-derived MHM V69 (i.e. the volume receiving?69Gy), GGM V35, ADM V60, MPC V49, and SPC V70 were associated with chronic-RAD. A model including age in addition to MHM V69 as continuous variables was optimal among tested MV models (AUC 0.835). CONCLUSION: In addition to SPCs, dose to MHM should be monitored and constrained, especially in older patients (>62-years), when feasible. PMID- 26897518 TI - TOPical Imiquimod treatment of high-grade Cervical intraepithelial neoplasia (TOPIC trial): study protocol for a randomized controlled trial. AB - BACKGROUND: Cervical intraepithelial neoplasia (CIN) is the premalignant condition of cervical cancer. Whereas not all high grade CIN lesions progress to cervical cancer, the natural history and risk of progression of individual lesions remain unpredictable. Therefore, high-grade CIN is currently treated by surgical excision: large loop excision of the transformation zone (LLETZ). This procedure has potential complications, such as acute haemorrhage, prolonged bleeding, infection and preterm birth in subsequent pregnancies. These complications could be prevented by development of a non-invasive treatment modality, such as topical imiquimod treatment. The primary study objective is to investigate the efficacy of topical imiquimod 5% cream for the treatment of high grade CIN and to develop a biomarker profile to predict clinical response to imiquimod treatment. Secondary study objectives are to assess treatment side effects, disease recurrence and quality of life during and after different treatment modalities. METHODS/DESIGN: The study design is a randomized controlled trial. One hundred forty women with a histological diagnosis of high-grade CIN (CIN 2-3) will be randomized into two arms: imiquimod treatment during 16 weeks (experimental arm) or immediate LLETZ (standard care arm). Treatment efficacy will be evaluated by colposcopy with diagnostic biopsies at 20 weeks for the experimental arm. Successful imiquimod treatment is defined as regression to CIN 1 or less, successful LLETZ treatment is defined as PAP 1 after 6 months. Disease recurrence will be evaluated by cytology at 6, 12 and 24 months after treatment. Side-effects will be evaluated using a standardized report form. Quality of life will be evaluated using validated questionnaires at baseline, 20 weeks and 1 year after treatment. Biomarkers, reflecting both host and viral factors in the pathophysiology of CIN, will be tested at baseline with the aim of developing a predictive biomarker profile for the clinical response to imiquimod treatment. DISCUSSION: Treatment of high-grade CIN lesions with imiquimod in a selected patient population may diminish complications as a result of surgical intervention. More knowledge on treatment efficacy, side effects and long-term recurrence rates after treatment is necessary. TRIAL REGISTRATION: EU Clinical Trials Register EU-CTR2013-001260-34 . Registered 18 March 2013. Medical Ethical Committee approval number: NL44336.068.13 (Medical Ethical Committee Maastricht University Hospital, University of Maastricht). Affiliation: Maastricht University Hospital. Registration number ClinicalTrials.gov: NCT02329171. PMID- 26897520 TI - Enhanced arsenite removal through surface-catalyzed oxidative coagulation treatment. AB - Arsenic being a naturally-occurring groundwater contaminant is subject to stringent water quality regulations. Coagulation and adsorption are widely used methods to treat arsenic-contaminated water, however, these treatments have been reported to be less efficient for the removal of arsenite (As(III)) than arsenate (As(V)). In this study, the feasibility of in situ oxidation of As(III) during coagulation was investigated in two systems: Fe(II) or H2O2-assisted oxidative coagulation treatment using ferric chloride as the coagulant. This setup exploits the catalytic property of the fresh formed Fe(III) hydroxide colloids in coagulation suspension to mediate the production of reactive oxidants capable of As(III) oxidation. Fe(II)-assisted coagulation brought about small improvements in As(III) removal compared to treatment with Fe(III) coagulant alone, however, its arsenic removal efficiency is strongly dependent on pH (observed optimal pH = 7-9). Addition of H2O2 together with ferric chloride led to a significant enhancement in arsenic retention at pH 6-8, with final arsenic concentrations well below the U.S.EPA regulatory limit (10 MUg/L). H2O2-assisted oxidative coagulation can attain reliable As(III) removal over a broad pH range of 4-9. Radical quenching experiments reveal the participation of superoxide radical in As(III) removal in the oxidative coagulation systems. Phosphate (at > 0.1 mM) strongly suppresses As(III) removal efficiency, whereas carbonate and humic acid pose a minor impact. Overall, the results suggest that a low dose addition of H2O2 along with ferric coagulant is a feasible method for the existing water treatment facilities to achieve improved As(III) removal efficiency. PMID- 26897522 TI - What does quality of care mean for maternal health providers from two vulnerable states of India? Case study of Bihar and Jharkhand. AB - BACKGROUND: Quality instillation has its own challenges, facilitators and barriers in various settings. This paper focuses on exploration of quality components related to practices, health system challenges and quality enablers from providers' perspectives with a focus on maternal health studied through a pilot research conducted in 2012-2013 in two states of India-Bihar and Jharkhand with relatively poor indicators for maternal health. METHODS: Qualitative data through in-depth interviews of 49 health providers purposively selected from various cadres of public health system in two districts each from Bihar and Jharkhand states was thematically analysed using MAXQDA Version 10. RESULTS: Maternity management guidelines developed by the National Health Mission, India, were considered as a tool to learn instillation of quality in provision of health services in various selected health facilities. Infrastructure, human resources, equipments and materials, drugs, training capacity and health information systems were described as health system challenges by medical and paramedical health providers. On a positive note, the study findings simultaneously identified quality enablers such as appreciation of public-private partnerships, availability of clinical guidelines in the form of wall posters in health facilities, efforts to translate knowledge and evidence through practice and enthusiasm towards value of guidelines. CONCLUSIONS: Against the backdrop of quality initiatives in the country to foster United Health Care (UHC), frontline health providers' perspectives about quality and safety need to be considered and utilized. The provision of adequate health infrastructure, strong health management information system, introduction of evidence-based education and training with supportive supervision must constitute parallel efforts. PMID- 26897521 TI - Vector competence of Aedes vexans (Meigen), Culex poicilipes (Theobald) and Cx. quinquefasciatus Say from Senegal for West and East African lineages of Rift Valley fever virus. AB - BACKGROUND: Rift Valley fever virus (RVFV; Phlebovirus, Bunyaviridae) is a mosquito-borne, zoonotic pathogen. In Senegal, RVFV was first isolated in 1974 from Aedes dalzieli (Theobald) and thereafter from Ae. fowleri (de Charmoy), Ae. ochraceus Theobald, Ae. vexans (Meigen), Culex poicilipes (Theobald), Mansonia africana (Theobald) and Ma. uniformis (Theobald). However, the vector competence of these local species has never been demonstrated making hypothetical the transmission cycle proposed for West Africa based on serological data and mosquito isolates. METHODS: Aedes vexans and Cx. poicilipes, two common mosquito species most frequently associated with RVFV in Senegal, and Cx. quinquefasciatus, the most common domestic species, were assessed after oral feeding with three RVFV strains of the West and East/central African lineages. Fully engorged mosquitoes (420 Ae. vexans, 563 Cx. quinquefasciatus and 380 Cx. poicilipes) were maintained at 27 +/- 1 degrees C and 70-80% relative humidity. The saliva, legs/wings and bodies were tested individually for the RVFV genome using real-time RT-PCR at 5, 10, 15 and 20 days post exposure (dpe) to estimate the infection, dissemination, and transmission rates. Genotypic characterisation of the 3 strains used were performed to identify factors underlying the different patterns of transmission. RESULTS: The infection rates varied between 30.0-85.0% for Ae. vexans, 3.3-27% for Cx. quinquefasciatus and 8.3-46.7% for Cx. poicilipes, and the dissemination rates varied between 10.5-37% for Ae. vexans, 9.5-28.6% for Cx. quinquefasciatus and 3.0-40.9% for Cx. poicilipes. However only the East African lineage was transmitted, with transmission rates varying between 13.3-33.3% in Ae. vexans, 50% in Cx. quinquefasciatus and 11.1% in Cx. poicilipes. Culex mosquitoes were less susceptible to infection than Ae. vexans. Compared to other strains, amino acid variation in the NSs M segment proteins of the East African RVFV lineage human-derived strain SH172805, might explain the differences in transmission potential. CONCLUSION: Our findings revealed that all the species tested were competent for RVFV with a significant more important role of Ae. vexans compared to Culex species and a highest potential of the East African lineage to be transmitted. PMID- 26897524 TI - Molecular detection of Mycobacterium bovis in cattle herds of the state of Pernambuco, Brazil. AB - BACKGROUND: The present study aimed to direct detect Mycobacterium bovis in milk (n = 401) and blood (n = 401) samples collected from 401 dairy cows of 20 properties located in the state of Pernambuco, Brazil, by real-time quantitative PCR (qPCR) targeting the region of difference 4 (RD4). Risk factors possibly associated with bovine tuberculosis (BTB) were also evaluated. RESULTS: Of the 802 samples analyzed, one milk (0.25%) and eight blood (2%) samples were positive for M. bovis in the qPCR and their identities were confirmed by sequencing. Animals positive for M. bovis were found in six (30%) of the 20 properties visited. None of the risk factors evaluated were statistically associated with BTB. CONCLUSIONS: M. bovis DNA was detected in one milk sample what may pose a risk to public health because raw milk is commonly consumed in Brazil. PMID- 26897525 TI - Fulminant proliferative diabetic retinopathy in the non-photocoagulated eye following acute renal failure. AB - Management of diabetic retinopathy should follow more strict and aggressive rules in patients at risk for severe acute renal impairment. Such patients should be identified and possibly prophylactically laser treated to avoid the severe consequences demonstrated in this case report. A 34-year-old type 2 diabetes patient with a stabilized diabetic retinopathy developed acute and severe retinal decompensation within weeks after acute renal failure complicated his chronic stable renal impairment. Fluorescein angiographic and optical coherence tomographic illustrations of the rapid evolution of the retinal condition are presented. The patient had previously been treated with panretinal photocoagulation in his left eye. After 8 years of regular 6-monthly checked stability, he developed rapid-onset proliferative diabetic retinopathy and macular edema in his right eye within 3 months of his last ocular check-up. Fluorescein angiography showed neovessels and major ischemic areas. Emergency panretinal photocoagulation and a sub-Tenon's injection were necessary to achieve control of the situation with regression of neovessels and complete regression of macular edema. This case shows that it is imperative for nephrologists to be well informed about a patient's ocular situation in order to give timely information to the ophthalmologist who can intervene to protect the retina in case of renal failure. On the other hand, the ophthalmologist should be familiar with the renal function of his patient with renal impairment so that he can decide to perform prophylactic retinal panphotocoagulation that should be imperatively considered even without strict indications in patients with renal impairment at risk for further deterioration of renal function, in order to prevent such explosive ischemic and proliferative retinopathy putting vision at risk. PMID- 26897523 TI - CD44-mediated monocyte transmigration across Cryptococcus neoformans-infected brain microvascular endothelial cells is enhanced by HIV-1 gp41-I90 ectodomain. AB - BACKGROUND: Cryptococcus neoformans (Cn) is an important opportunistic pathogen in the immunocompromised people, including AIDS patients, which leads to fatal cryptococcal meningitis with high mortality rate. Previous researches have shown that HIV-1 gp41-I90 ectodomain can enhance Cn adhesion to and invasion of brain microvascular endothelial cell (BMEC), which constitutes the blood brain barrier (BBB). However, little is known about the role of HIV-1 gp41-I90 in the monocyte transmigration across Cn-infected BBB. In the present study, we provide evidence that HIV-1 gp41-I90 and Cn synergistically enhance monocytes transmigration across the BBB in vitro and in vivo. The underlying mechanisms for this phenomenon require further study. METHODS: In this study, the enhancing role of HIV-1 gp41-I90 in monocyte transmigration across Cn-infected BBB was demonstrated by performed transmigration assays in vitro and in vivo. RESULTS: Our results showed that the transmigration rate of monocytes are positively associated with Cn and/or HIV-1 gp41-I90, the co-exposure (HIV-1 gp41-I90 + Cn) group showed a higher THP-1 transmigration rate (P < 0.01). Using CD44 knock-down HBMEC or CD44 inhibitor Bikunin in the assay, the facilitation of transmigration rates of monocyte enhanced by HIV-1 gp41-I90 was significantly suppressed. Western blotting analysis and biotin/avidin enzyme-linked immunosorbent assays (BA ELISAs) showed that Cn and HIV-1 gp41-I90 could increase the expression of CD44 and ICAM-1 on the HBMEC. Moreover, Cn and/or HIV-1 gp41-I90 could also induce CD44 redistribution to the membrane lipid rafts. By establishing the mouse cryptococcal meningitis model, we found that HIV-1 gp41-I90 and Cn could synergistically enhance the monocytes transmigration, increase the BBB permeability and injury in vivo. CONCLUSIONS: Collectively, our findings suggested that HIV-1 gp41-I90 ectodomain can enhance the transmigration of THP-1 through Cn-infected BBB, which may be mediated by CD44. This novel study enlightens the future prospects to elaborate the inflammatory responses induced by HIV-1 gp41-I90 ectodomain and to effectively eliminate the opportunistic infections in AIDS patients. PMID- 26897526 TI - Interferon-induced transmembrane protein 1 (IFITM1) overexpression enhances the aggressive phenotype of SUM149 inflammatory breast cancer cells in a signal transducer and activator of transcription 2 (STAT2)-dependent manner. AB - BACKGROUND: Inflammatory breast cancer (IBC) is a very aggressive and lethal subtype of breast cancer that accounts for about 4 % of all breast cancers diagnosed in the United States. Despite the efforts of several investigators to identify the molecular factors driving the aggressive phenotype of IBC, a great deal is still unknown about the molecular underpinnings of the disease. In the present study, we investigated the role of interferon-induced transmembrane protein 1 (IFITM1), a well-known interferon-stimulated gene (ISG), in promoting the aggressiveness of SUM149 IBC cells. METHODS: Western blot and real-time polymerase chain reaction analyses were performed to assess the protein and messenger RNA (mRNA) levels of IFITM1 and other ISGs in three IBC cell lines: SUM149, MDA-IBC-3, and SUM190. IFITM1 expression and cellular localization were assessed by using immunofluorescence, while the tumorigenic potential was assessed by performing cell migration, invasion, and colony formation assays. Small interfering RNA and short hairpin RNA knockdowns, enzyme-linked immunosorbent assays, and luciferase assays were performed to determine the functional significance of IFITM1 and signal transducers and activators of transcription 1 and 2 (STAT1/2) in SUM149 cells. RESULTS: We found that IFITM1 was constitutively overexpressed at the mRNA and protein levels in triple negative SUM149 IBC cells, but that it was not expressed in SUM190 and MDA-IBC-3 IBC cells, and that suppression of IFITM1 or blockade of the IFNalpha signaling pathway significantly reduced the aggressive phenotype of SUM149 cells. Additionally, we found that knockdown of STAT2 abolished IFITM1 expression and IFITM1 promoter activity in SUM149 cells and that loss of STAT2 significantly inhibited the ability of SUM149 cells to proliferate, migrate, invade, and form 2 D colonies. Notably, we found that STAT2-mediated activation of IFITM1 was particularly dependent on the chromatin remodeler brahma-related gene 1 (BRG1), which was significantly elevated in SUM149 cells compared with SUM190 and MDA-IBC 3 cells. CONCLUSIONS: These findings indicate that overexpression of IFITM1 enhances the aggressive phenotype of triple-negative SUM149 IBC cells and that this effect is dependent on STAT2/BRG1 interaction. Further studies are necessary to explore the potential of IFITM1 as a novel therapeutic target and prognostic marker for some subtypes of IBCs. PMID- 26897528 TI - Three-dimensional volumetric MRI with isotropic resolution: improved speed of acquisition, spatial resolution and assessment of lesion conspicuity in patients with recurrent soft tissue sarcoma. AB - BACKGROUND: To assess the acquisition speed, lesion conspicuity, and inter observer agreement associated with volumetric T(1)-weighted MR sequences with isotropic resolution for detecting recurrent soft-tissue sarcoma (STS). METHODS: Fifteen subjects with histologically proven recurrent STS underwent MRI, including axial and coronal T(1)-weighted spin echo (T(1)-WSE) (5-mm slice thickness) and coronal 3D volumetric T(1)-weighted (fat-suppressed, volume interpolated, breath-hold examination; repetition time/echo time, 3.7/1.4 ms; flip angle, 9.5 degrees ; 1-mm slice thickness) sequences before and after intravenous contrast administration. Subtraction imaging and multiplanar reformations (MPRs) were performed. Acquisition times for T(1)-WSE in two planes and 3D sequences were reported. Two radiologists reviewed images for quality (>50 % artifacts, 25-50 % artifacts, <25 % artifacts, and no substantial artifacts), lesion conspicuity, contrast-to-noise ratio (CNR(muscle)), recurrence size, and recurrence-to-joint distance. Descriptive and intraclass correlation (ICC) statistics are given. RESULTS: Mean acquisition times were significantly less for 3D imaging compared with 2-plane T(1)-WSE (183.6 vs 342.6 s; P = 0.012). Image quality was rated as having no substantial artifacts in 13/15 and <25 % artifacts in 2/15. Lesion conspicuity was significantly improved for subtracted versus unsubtracted images (CNR(muscle), 100 +/- 138 vs 181 +/- 199; P = 0.05). Mean recurrent lesion size was 2.5 cm (range, 0.7-5.7 cm), and measurements on 3D sequences offered excellent interobserver agreement (ICC, 0.98 for lesion size and 0.96 for recurrence-to-joint distance with MPR views). CONCLUSION: Three dimensional volumetric sequences offer faster acquisition times, higher spatial resolution, and MPR capability compared with 2D T(1)-WSE for postcontrast imaging. Subtraction imaging provides higher lesion conspicuity for detecting recurrent STS in skeletal muscle, with excellent interobserver agreement between readers. PMID- 26897527 TI - Phytohormone balance and stress-related cellular responses are involved in the transition from bud to shoot growth in leafy spurge. AB - BACKGROUND: Leafy spurge (Euphorbia esula L.) is an herbaceous weed that maintains a perennial growth pattern through seasonal production of abundant underground adventitious buds (UABs) on the crown and lateral roots. During the normal growing season, differentiation of bud to shoot growth is inhibited by physiological factors external to the affected structure; a phenomenon referred to as paradormancy. Initiation of shoot growth from paradormant UABs can be accomplished through removal of the aerial shoots (hereafter referred to as paradormancy release). RESULTS: In this study, phytohormone abundance and the transcriptomes of paradormant UABs vs. shoot-induced growth at 6, 24, and 72 h after paradormancy release were compared based on hormone profiling and RNA-seq analyses. Results indicated that auxin, abscisic acid (ABA), and flavonoid signaling were involved in maintaining paradormancy in UABs of leafy spurge. However, auxin, ABA, and flavonoid levels/signals decreased by 6 h after paradormancy release, in conjunction with increase in gibberellic acid (GA), cytokinin, jasmonic acid (JA), ethylene, and brassinosteroid (BR) levels/signals. Twenty four h after paradormancy release, auxin and ABA levels/signals increased, in conjunction with increase in GA levels/signals. Major cellular changes were also identified in UABs at 24 h, since both principal component and Venn diagram analysis of transcriptomes clearly set the 24 h shoot-induced growth apart from other time groups. In addition, increase in auxin and ABA levels/signals and the down-regulation of 40 over-represented AraCyc pathways indicated that stress derived cellular responses may be involved in the activation of stress-induced re orientation required for initiation of shoot growth. Seventy two h after paradormancy release, auxin, cytokinin, and GA levels/signals were increased, whereas ABA, JA, and ethylene levels/signals were decreased. CONCLUSION: Combined results were consistent with different phytohormone signals acting in concert to direct cellular changes involved in bud differentiation and shoot growth. In addition, shifts in balance of these phytohormones at different time points and stress-related cellular responses after paradormancy release appear to be critical factors driving transition of bud to shoot growth. PMID- 26897529 TI - NMR assignments of mitochondrial cyclophilin Cpr3 from Saccharomyces cerevisiae. AB - Cyclophilins regulate protein folding, transport and signalling through catalysis of proline isomerization, and are ubiquitously expressed in both prokaryotes and eukaryotes. Cpr3 is the yeast mitochondrial cyclophilin and it is structurally and biophysically uncharacterized so far. Yeast cyclophilin gene cpr3 is essential for the lactate metabolism. Here, we report (1)H, (13)C, and (15)N chemical shift assignments of Cpr3 protein determined by various 2D and 3D heteronuclear NMR experiments at pH 6.5, and temperature 298 K. PMID- 26897530 TI - Cake-like material within the pericardium: an unusual picture of pyopericardium. PMID- 26897531 TI - The Influence of Training, Reluctance, Efficacy, and Stigma on Suicide Intervention Behavior Among NCOs in the Army and Marine Corps. AB - The Army and Marine Corps have consistently experienced the highest rates of suicide relative to the other services. In both the Army and Marine Corps, the service members responsible for identifying and referring individuals at risk for suicide are called "gatekeepers" and are typically noncommissioned officers (NCOs). We used structural equation modeling on survey responses from 1184 Army soldiers and 796 marines to estimate the relationships between training, intervention efficacy, reluctance, and mental health stigma on NCO intervention behaviors. Efficacy and reluctance were independently associated with intervention behaviors, and stigma was only associated with intervention behaviors among Army NCOs. Study results suggest that while quantity of training may help NCOs feel more confident about their ability to intervene, other efforts such as changing training content and delivery mode (e.g., interactive vs. didactic training) may be necessary in order to reduce reluctance and stigma to intervene with service members at risk for suicide. PMID- 26897532 TI - Innovative biomarkers for predicting type 2 diabetes mellitus: relevance to dietary management of frailty in older adults. AB - Type 2 diabetes mellitus (T2DM) increases in prevalence in the elderly. There is evidence for significant muscle loss and accelerated cognitive impairment in older adults with T2DM; these comorbidities are critical features of frailty. In the early stages of T2DM, insulin sensitivity can be improved by a "healthy" diet. Management of insulin resistance by diet in people over 65 years of age should be carefully re-evaluated because of the risk for falling due to hypoglycaemia. To date, an optimal dietary programme for older adults with insulin resistance and T2DM has not been described. The use of biomarkers to identify those at risk for T2DM will enable clinicians to offer early dietary advice that will delay onset of disease and of frailty. Here we have used an in silico literature search for putative novel biomarkers of T2DM risk and frailty. We suggest that plasma bilirubin, plasma, urinary DPP4-positive microparticles and plasma pigment epithelium-derived factor merit further investigation as predictive biomarkers for T2DM and frailty risk in older adults. Bilirubin is screened routinely in clinical practice. Measurement of specific microparticle frequency in urine is less invasive than a blood sample so is a good choice for biomonitoring. Future studies should investigate whether early dietary changes, such as increased intake of whey protein and micronutrients that improve muscle function and insulin sensitivity, affect biomarkers and can reduce the longer term complication of frailty in people at risk for T2DM. PMID- 26897533 TI - Cyclic three-dimensional wall motion of the human ascending and abdominal aorta characterized by time-resolved three-dimensional ultrasound speckle tracking. AB - The aim of this study was to measure, characterize, and compare the time-resolved three-dimensional wall kinematics of the ascending and the abdominal aorta. Comprehensive description of aortic wall kinematics is an important issue for understanding its physiological functioning and early detection of adverse changes. Data on the three-dimensional, dynamic cyclic deformation of the aorta in vivo are scarce. Either most imaging techniques available are too slow to capture aortic wall motion (CT, MRI) or they do not provide three-dimensional geometry data. Three-dimensional volume data sets of ascending and abdominal aortae of male healthy subjects (25.5 [24.5, 27.5] years) were acquired by use of a commercial echocardiography system with a temporal resolution of 11-25 Hz. Longitudinal and circumferential strain, twist, and relative volume change were determined by use of a commercial speckle tracking algorithm and in-house software. The kinematics of the abdominal aorta is characterized by diameter change, almost constant length and unidirectional, either clockwise or counter clockwise twist. In contrast, the ascending aorta undergoes a complex deformation with alternating clockwise and counterclockwise twist. Length and diameter changes were in the same order of magnitude with a phase shift between both. Longitudinal strain and its phase shift to circumferential strain contribute to the proximal aorta's Windkessel function. Complex cyclic deformations are known to be highly fatiguing. This may account for increased degradation of components of the aortic wall and therefore promote aortic dissection or aneurysm formation. PMID- 26897534 TI - Chlorella vulgaris production enhancement with supplementation of synthetic medium in dairy manure wastewater. AB - To identify innovative ways for better utilizing flushed dairy manure wastewater, we have assessed the effect of dairy manure and supplementation with synthetic medium on the growth of Chlorella vulgaris. A series of experiments were carried out to study the impacts of pretreatment of dairy wastewater and the benefits of supplementing dairy manure wastewater with synthetic medium on C. vulgaris growth increment and the ultrastructure (chloroplast, starch, lipid, and cell wall) of C. vulgaris cells. Results showed that the biomass production of C. vulgaris in dairy wastewater can be enhanced by pretreatment and using supplementation with synthetic media. A recipe combining pretreated dairy wastewater (40 %) and synthetic medium (60 %) exhibited an improved growth of C. vulgaris. The effects of dairy wastewater on the ultrastructure of C. vulgaris cells were distinct compared to that of cells grown in synthetic medium. The C. vulgaris growth in both synthetic medium and manure wastewater without supplementing synthetic medium was lower than the growth in dairy manure supplemented with synthetic medium. We anticipate that the results of this study will help in deriving an enhanced method of coupling nutrient-rich dairy manure wastewater for biofuel production. PMID- 26897535 TI - Is thyroid status associated with cognitive impairment in elderly patients in China? AB - BACKGROUND: The relationship between alterations in thyroid function and cognitive deficits has been investigated in several previous studies. Hypo-or hyperthyroidism and, to a lesser extent, subclinical thyroid dysfunction can negatively affect cognitive performance. However, limited data are available on the potential association of thyroid function with mild cognitive impairment (MCI) and Alzheimer's disease (AD) in the elderly Chinese population. METHODS: In the present study focusing on a population of elderly Chinese individuals >= 50 years of age, 77 cognitively normal controls, 64 patients with MCI, and 154 patients diagnosed with AD underwent assessment of thyroid status using thyroid stimulating hormone (TSH), free triiodothyronine (fT3) and free thyroxine (fT4) levels as variables. Cognitive function was evaluated with the aid of comprehensive neuropsychological tests, such as the Mini-Mental State Examination (MMSE) and Memory and Executive Screening (MES). RESULTS: Overall, 88.1 % of the subjects displayed normal thyroid function, 4.7 % were diagnosed with clinical hypothyroidism, 3.1 % with subclinical hypothyroidism, and 4.1 % with subclinical hyperthyroidism. After adjusting for covariates (age, sex, education years and body mass index), no association was evident between mild cognitive impairment or AD and thyroid dysfunction. However, lower serum TSH was correlated with risk of AD (odds ratio [OR]: 2.78, 95 % confidence interval [95% CI]: 1.11-6.99). CONCLUSION: Neither hypothyroidism nor subclinical hyperthyroidism was associated with AD and MCI in this population-based elderly Chinese cohort. Our findings need to be confirmed in a longitudinal study. PMID- 26897536 TI - Simple and versatile synthetic polydopamine-based surface supports reprogramming of human somatic cells and long-term self-renewal of human pluripotent stem cells under defined conditions. AB - Human pluripotent stem cells (hPSCs) possess great value in the aspect of cellular therapies due to its self-renewal and potential to differentiate into all somatic cell types. A few defined synthetic surfaces such as polymers and adhesive biological materials conjugated substrata were established for the self renewal of hPSCs. However, none of them was effective in the generation of human induced pluripotent stem cells (hiPSCs) and long-term maintenance of multiple hPSCs, and most of them required complicated manufacturing processes. Polydopamine has good biocompatibility, is able to form a stable film on nearly all solid substrates surface, and can immobilize adhesive biomolecules. In this manuscript, a polydopamine-mediated surface was developed, which not only supported the reprogramming of human somatic cells into hiPSCs under defined conditions, but also sustained the growth of hiPSCs on diverse substrates. Moreover, the proliferation and pluripotency of hPSCs cultured on the surface were comparable to Matrigel for more than 20 passages. Besides, hPSCs were able to differentiate to cardiomyocytes and neural cells on the surface. This polydopamine-based synthetic surface represents a chemically-defined surface extensively applicable both for fundamental research and cell therapies of hPSCs. PMID- 26897537 TI - Electroactive biodegradable polyurethane significantly enhanced Schwann cells myelin gene expression and neurotrophin secretion for peripheral nerve tissue engineering. AB - Myelination of Schwann cells (SCs) is critical for the success of peripheral nerve regeneration, and biomaterials that can promote SCs' neurotrophin secretion as scaffolds are beneficial for nerve repair. Here we present a biomaterials approach, specifically, a highly tunable conductive biodegradable flexible polyurethane by polycondensation of poly(glycerol sebacate) and aniline pentamer, to significantly enhance SCs' myelin gene expression and neurotrophin secretion for peripheral nerve tissue engineering. SCs are cultured on these conductive polymer films, and the biocompatibility of these films and their ability to enhance myelin gene expressions and sustained neurotrophin secretion are successfully demonstrated. The mechanism of SCs' neurotrophin secretion on conductive films is demonstrated by investigating the relationship between intracellular Ca(2+) level and SCs' myelination. Furthermore, the neurite growth and elongation of PC12 cells are induced by adding the neurotrophin medium suspension produced from SCs-laden conductive films. These data suggest that these conductive degradable polyurethanes that enhance SCs' myelin gene expressions and sustained neurotrophin secretion perform great potential for nerve regeneration applications. PMID- 26897538 TI - Effective antimicrobial activity of Cbf-14, derived from a cathelin-like domain, against penicillin-resistant bacteria. AB - Cbf-14, a cationic peptide derived from a cathelin-like domain, was designed by inserting the highly alpha-helical sequence RLLR into an antibacterial sequence and deleting the inactive amino acids in Cbf-K16. Clinical penicillin-resistant isolates as well as NDM-1-carrying Escherichia coli and a correspondingly infected mice model were employed to evaluate Cbf-14 antibacterial activity. The results showed that Cbf-14 possessed potent antimicrobial effects with an MIC of 8-64 MUg/ml, and killed almost all bacteria within 240 min. Cbf-14-treated mice achieved an 80% survival rate and approximate 2.5 log unit reduction in CFU in tissues; additionally, this peptide significantly suppressed the production of pro-inflammatory cytokines by the disaggregation of lipopolysaccharide (LPS), suggesting its anti-inflammatory effects. Furthermore, Cbf-14, concentration higher than 2 * MIC value, increased membrane uptake to NPN and PI dye by 96.2% and 63.7%, respectively, neutralised the negative zeta potential of LPS and bacteria surface, and induced 100% leakage of liposome-entrapped calcein and cytoplasmic membrane disruption of E. coli, indicating obvious membrane permeation. Finally, it bound to DNA and respectively evoked 85.0% and 63.3% inhibition of gene replication and protein expression of NDM-1 at sub-MIC concentration in E. coli BL21 (DE3)-NDM-1. These data indicated that Cbf-14 possessed effective antimicrobial activity against penicillin-resistant bacteria in vitro/vivo through membrane disruption, DNA binding, down-regulating NDM-1 expression by plasmid replication inhibition, and anti-inflammatory activity by LPS disaggregation, suggesting a potential anti-infective clinical agent. PMID- 26897539 TI - Enhanced immunotherapy of SM5-1 in hepatocellular carcinoma by conjugating with gold nanoparticles and its in vivo bioluminescence tomographic evaluation. AB - SM5-1 is a humanized mouse monoclonal antibody, targeting an over-expressed membrane protein of approximately 230 kDa in hepatocellular carcinoma (HCC). SM5 1 can be used for target therapy in hepatocellular carinoma due to its ability of inhibiting cell growth and inducing apoptosis. However, the tumor inhibition efficacy of SM5-1 in HCC cancer treatment remains low. In this study, we synthesized SM5-1-conjugated gold nanoparticles (Au-SM5-1 NPs) and investigated their anticancer efficacy in HCC both in vitro and in vivo. The tumor inhibition rates of Au-SM5-1 NPs for subcutaneous tumor mice were 40.10% +/- 4.34%, 31.37% +/- 5.12%, and 30.63% +/- 4.87% on day 12, 18, and 24 post-treatment as determined by bioluminescent intensity. In addition, we investigated the antitumor efficacy of Au-SM5-1 NPs in orthotopic HCC tumor models. The results showed that the inhibition rates of Au-SM5-1 NPs can reach up to 39.64% +/- 4.87% on day 31 post-treatment determined by the bioluminescent intensity of the abdomen in tumor-bearing mice. Furthermore, three-dimensional reconstruction results of the orthotopic tumor revealed that Au-SM5-1 NPs significantly inhibited tumor growth compared with SM5-1 alone. Our results suggested that the developed Au-SM5-1 NPs has great potential as an antibody-based nano-drug for HCC therapy. PMID- 26897541 TI - A regular narrow QRS tachycardia in a young man. PMID- 26897540 TI - New approaches to qualitative interviewing: Development of a card sort technique to understand subjective patterns of symptoms and responses. AB - BACKGROUND: Ability to elicit individuals' perceptions of complex behavioral processes can be challenging, as it hinges not only upon the skill of the researcher, but also upon assumptions of a shared language and individuals' ability to recall, analyze, and effectively communicate events. In a case-based qualitative-descriptive study about teens' experiences of asthma self-management, we found that variations in terminology and descriptions of events, symptoms, and responses made it difficult to understand teens' experiences of asthma. In particular, teens' conceptualization of their asthma symptoms and self-management responses differed from situation to situation, from other teens in the study, from the interviewer, and from prior reports in the literature. These differences across many levels made it difficult to identify patterns in individual processes of self-management, and among teens in general.. OBJECTIVES: To address these challenges, we developed a card sorting activity to facilitate in-depth exploration of teens' experiences of asthma. DESIGN: Case-based qualitative description. SETTING: Teen-parent dyads (N=28) were recruited from the community, Emergency Department, Pediatric Pulmonary Department, and prior study subjects of a major medical center. METHODS: Teens first identified and then sequenced their own unique sets of asthma symptoms and self-management responses. Teens then developed contextually grounded narratives using the card sort they had created as a visual aid. RESULTS: This technique not only allowed us to bridge teen interviewer communication barriers and develop shared terminology, but also resulted in a visible sequence of asthma symptoms and self-management responses. CONCLUSIONS: The card sort technique facilitated researcher-teen discussion and enabled comparison of self-management patterns across teens in our study. This technique is potentially useful for other areas of research exploring behavioral processes with complex and individual-specific experiences, in particular those involving sequences of events and self-management responses. This paper delineates the development, utility, and potential applications of the symptom response card sorting technique for research and clinical practice. PMID- 26897542 TI - The spectrum of long-term cognitive and functional outcome after hemispherectomy in childhood. AB - PURPOSE: To evaluate cognition, behavior, daily functioning and health-related quality of life (HrQoL) five years to more than a decade after hemispherectomy (HE) in childhood. METHODS: This countrywide Dutch cohort study of 31 patients, who underwent HE between 1994 and 2009, included a semi-structured interview with parents, an assessment of cognition, and screening of behavioral problems and HrQoL. RESULTS: Twenty-two school-age children and young adults [median age 13.8 years (0.5 at epilepsy onset, 5.3 at HE)] were assessed with age-appropriate cognitive tests. IQ ranged from 45 to 82 (median 61). Despite performing below mean norm scores, these participants could learn and remember, sustain attention, inhibit irrelevant responses, read and write. Nine more children [median age 9.7 years (0.25 at epilepsy onset, 1.4 at HE)] were so mentally retarded that age appropriate testing was impossible. This group was almost totally dependent on others in daily activities, had the highest proportion of pre-existing contralateral MRI-abnormalities and after HE the highest rates of seizure recurrence and behavioral problems. Parents in both groups rated HrQoL surprisingly positively (mean VAS-score 72.5), with a scarce low rating (40). All parents reported problems with respect to their children's self-care, daily activities and mobility. CONCLUSION: At least five years after HE, cognitive, behavioral and daily functioning encompasses a broad spectrum that varies from profound retardation and almost total dependence to low normal cognition and a reasonably independent existence. Pre-existing contralateral MRI abnormalities reflect a more generally affected brain with a limited ability to mediate development after HE. PMID- 26897544 TI - Reduction of Risk Factors in Patients with Behavioral Dysphonia After Vocal Group Therapy. AB - OBJECTIVES: The origin and development of dysphonia, particularly behavioral dysphonia, is associated with several risk factors. Here, we verified the effectiveness of group therapy in reducing the risk factors, and established the association between risk factors and sex, age, profession, and diagnosis of laryngeal disorders in patients with behavioral dysphonia. STUDY DESIGN: This is a descriptive, quantitative, field intervention study. METHODS: Participants (n = 26, adult patients of both sexes), with a diagnosis of behavioral dysphonia, received group therapy intervention. Data for risk factors were collected pre- and posttherapy using the Vocal Screening Protocol. The data were analyzed using descriptive and inferential statistics (Student t test, chi-squared test or Spearman correlation test). RESULTS: The majority (80.8%, n = 21) of patients were female, 65.4% (n = 17) were not in a vocal profession, and 42.3% (n = 11) presented with a lesion in the membranous portion of the vocal fold. The number of personal risk factors decreased after group therapy (P = 0.04). In addition, age was correlated with total (P = 0.001), environmental (P = 0.002), and personal (P = 0.003) vocal risk factors posttherapy. CONCLUSIONS: This study revealed an association between the reduction of personal risk factors and vocal group therapy, and a correlation between age and total, environmental, and personal vocal risk factors posttherapy. Thus, maintenance and origins of the behaviors that modify the behavioral aspects of the participants directly influence the production of individual vocal habits. PMID- 26897545 TI - Assessments of Voice Use and Voice Quality Among College/University Singing Students Ages 18-24 Through Ambulatory Monitoring With a Full Accelerometer Signal. AB - The multiple social and performance demands placed on college/university singers could put their still-developing voices at risk. Previous ambulatory monitoring studies have analyzed the duration, intensity, and frequency (in Hertz) of voice use among such students. Nevertheless, no studies to date have incorporated the simultaneous acoustic voice quality measures into the acquisition of these measures to allow for direct comparison during the same voicing period. Such data could provide greater insight into how young singers use their voices, as well as identify potential correlations between vocal dose and acoustic changes in voice quality. The purpose of this study was to assess the voice use and the estimated voice quality of college/university singing students (18-24 years old, N = 19). Ambulatory monitoring was conducted over three full, consecutive weekdays measuring voice from an unprocessed accelerometer signal measured at the neck. From this signal, traditional vocal dose metrics such as phonation percentage, dose time, cycle dose, and distance dose were analyzed. Additional acoustic measures included perceived pitch, pitch strength, long-term average spectrum slope, alpha ratio, dB sound pressure level 1-3 kHz, and harmonic-to-noise ratio. Major findings from more than 800 hours of recording indicated that among these students (a) higher vocal doses correlated significantly with greater voice intensity, more vocal clarity and less perturbation; and (b) there were significant differences in some acoustic voice quality metrics between nonsinging, solo singing, and choral singing. PMID- 26897547 TI - Treatment non-adherence in pseudo-refractory epilepsy. AB - Non-adherence to antiepileptic drug treatment strongly affects the outcome of epilepsy and is frequently clinically unrecognized. This review addresses current knowledge on medication-taking behavior in people with epilepsy, as well as the importance of tailoring interventions to the individual patterns of non adherence. Non-adherence can be categorized as non-initiation, poor execution (accidental or intentional) or non-persistence and are related to clinical characteristics and health care barriers. All available methods to assess adherence are hampered by shortcomings. Self-reports are indirect and subjective. Pill-counts, electronic bottle-tops and pharmacy records are objective, but indirect measures of drug ingestion. Therapeutic drug monitoring is both direct and objective, but pharmacokinetic and diurnal variability must be taken into account. Young adults with generalized epilepsy may be particularly vulnerable to non-adherence. The drug burden in the form of polytherapy, multiple dosing and side effects are obvious obstacles. Poor understanding of the principles of prophylactic treatment as well as drug costs may be important in people with low socioeconomic status. Depression is also associated with low adherence. In people with multihandicaps, failed oral intake may be due to behavioral or physical problems, as well as insufficient education of the caregivers. Non-adherence often results in seizure breakthrough and hospital admissions, but the consequences may be more dramatic. It is the leading cause of status epilepticus in people with epilepsy, and the association with sudden death (SUDEP) is clear. The management of poor drug-taking behavior should be based on the identification of the specific causes in each individual and corresponding multiprofessional interventions. Non-adherence to antiepileptic drugs needs more clinical and scientific attention. PMID- 26897548 TI - Insights into the Functions of M-T Hook Structure in HIV Fusion Inhibitor Using Molecular Modeling. AB - HIV-1 membrane fusion plays an important role in the process that HIV-1 entries host cells. As a treatment strategy targeting HIV-1 entry process, fusion inhibitors have been proposed. Nevertheless, development of a short peptide possessing high anti-HIV potency is considered a daunting challenge. He et al. found that two residues, Met626 and Thr627, located the upstream of the C terminal heptad repeat of the gp41, formed a unique hook-like structure (M-T hook) that can dramatically improve the binding stability and anti-HIV activity of the inhibitors. In this work, we explored the molecular mechanism why M-T hook structure could improve the anti-HIV activity of inhibitors. Firstly, molecular dynamic simulation was used to obtain information on the time evolution between gp41 and ligands. Secondly, based on the simulations, molecular mechanics Poisson Boltzmann surface area (MM-PBSA) and molecular mechanics Generalized Born surface area (MM-GBSA) methods were used to calculate the binding free energies. The binding free energy of the ligand with M-T hook was considerably higher than the other without M-T. Further studies showed that the hydrophobic interactions made the dominant contribution to the binding free energy. The numbers of Hydrogen bonds between gp41 and the ligand with M-T hook structure were more than the other. These findings should provide insights into the inhibition mechanism of the short peptide fusion inhibitors and be useful for the rational design of novel fusion inhibitors in the future. PMID- 26897546 TI - Bilateral neuroinflammatory processes in visual pathways induced by unilateral ocular hypertension in the rat. AB - BACKGROUND: Glaucoma is one of the leading causes of irreversible blindness in the world. The major risk factor is elevated intraocular pressure (IOP) leading to progressive retinal ganglion cell (RGC) death from the optic nerve (ON) to visual pathways in the brain. Glaucoma has been reported to share mechanisms with neurodegenerative disorders. We therefore hypothesize that neuroinflammatory mechanisms in central visual pathways may contribute to the spread of glaucoma disease. The aim of the present study was to analyze the neuroinflammation processes that occur from the pathological retina to the superior colliculi (SCs) in a rat model of unilateral ocular hypertension induced by episcleral vein cauterization (EVC). RESULTS: Six weeks after unilateral (right eye) EVC in male Long-Evans rats, we evaluated both the neurodegenerative process and the neuroinflammatory state in visual pathway tissues. RGCs immunolabeled (Brn3a(+)) in ipsilateral whole flat-mounted retina demonstrated peripheral RGC loss associated with tissue macrophage/microglia activation (CD68(+)). Gene expression analysis of hypertensive and normotensive retinas revealed a significant increase of pro-inflammatory genes such as CCL2, IL-1beta, and Nox2 mRNA expression compared to naive eyes. Importantly, we found an upregulation of pro-inflammatory markers such as IL-1beta and TNFalpha and astrocyte and tissue macrophage/microglia activation in hypertensive and normotensive RGC projection sites in the SCs compared to a naive SC. To understand how neuroinflammation in the hypertensive retina is sufficient to damage both right and left SCs and the normotensive retina, we used an inflammatory model consisting in an unilateral stereotaxic injection of TNFalpha (25 ng/MUl) in the right SC of naive rats. Two weeks after TNFalpha injection, using an optomotor test, we observed that rats had visual deficiency in both eyes. Furthermore, both SCs showed an upregulation of genes and proteins for astrocytes, microglia, and pro-inflammatory cytokines, notably IL-1beta. In addition, both retinas exhibited a significant increase of inflammatory markers compared to a naive retina. CONCLUSIONS: All these data evidence the complex role played by the SCs in the propagation of neuroinflammatory events induced by unilateral ocular hypertension and provide a new insight into the spread of neurodegenerative diseases such as glaucoma. PMID- 26897550 TI - Self-organization of gliadin in aqueous media under physiological digestive pHs. AB - Here we showed that gliadin, a complex protein system related to celiac disease and other human diseases, is spontaneously self-organized in a very dilute solution at pH 3.0 and 7.0 in water under low ionic strength (10mM NaCl). The spontaneous self-organization at pH 3.0 increases the apparent solubility due to the formation of finite sized aggregates, such as those formed in the micellization of amphiphilic molecules. Switching the pH from 3.0 to 7.0 lead to a phase separation, however part of the nano-particles are stable remaining disperse in water after centrifugation. Also, beside the pH change led to changes in protein composition and concentration, we determined that the secondary structure of both system is the same. Moreover, Tyrs are slightly more buried and Trps are slightly more exposed to water at pH 7.0 than those at pH 3.0. Electron microscopy techniques showed that both gliadin systems are composed of nanostructures and in the case of pH 7.0 amorphous microaggregates were found, too. Only nanostructures at pH 3.0 showed a micromolar binding affinity to Nile red probe, suggesting the presence of accessible hydrophobic patches which are not more accessible at pH 7.0. All our results suggest that gliadin is able to self-organized at pH 3.0 forming protein micelles type nanostructures (zeta=+13, 42 +/- 1.55 mV), meanwhile at 7.0 the decrease of superficial charge to zeta of +4, 78 +/- 0.48 mV led to the formation of stable colloidal nanoparticles, unable to interact with Nile red probe. Our findings may open new perspectives for the understanding of gliadin ability to avoid proteolysis, to reach and cross the intestinal lumen and to trigger different immunological disorders. PMID- 26897549 TI - Towards efficient photosynthesis: overexpression of Zea mays phosphoenolpyruvate carboxylase in Arabidopsis thaliana. AB - Plants with C4 photosynthesis are efficient in carbon assimilation and have an advantage over C3 photosynthesis. In C4 photosynthesis, the primary CO2 fixation is catalyzed by phosphoenolpyruvate carboxylase (PEPC). Here, we show that overexpression of Zea mays PEPC cDNA, under the control of 35S promoter, in Arabidopsis thaliana resulted in ~7-10 fold higher protein abundance and ~7-10 fold increase in PEPC activity in the transgenic lines than that in the vector control. We suggest that overexpression of PEPC played an anaplerotic role to increase the supply of 4-carbon carboxylic acids, which provided carbon skeletons for increased amino acid and protein synthesis. Higher protein content must have been responsible for increased metabolic processes including chlorophyll biosynthesis, photosynthesis, and respiration. Consequently, the PEPC overexpressed transgenic plants had higher chlorophyll content, enhanced electron transport rate (ETR), lower non-photochemical quenching (NPQ) of chlorophyll a fluorescence, and a higher performance index (PI) than the vector control. Consistent with these observations, the rate of CO2 assimilation, the starch content, and the dry weight of PEPC-overexpressed plants increased by 14-18 %, 10 18 %, and 6.5-16 %, respectively. Significantly, transgenics were tolerant to salt stress as they had increased ability to synthesize amino acids, including the osmolyte proline. NaCl (150 mM)-treated transgenic plants had higher variable to maximum Chl a fluorescence (F v/F m) ratio, higher PI, higher ETR, and lower NPQ than the salt-treated vector controls. These results suggest that expression of C4 photosynthesis enzyme(s) in a C3 plant can improve its photosynthetic capacity with enhanced tolerance to salinity stress. PMID- 26897551 TI - Development and characterization of an innovative heparin coating to stabilize and protect liposomes against adverse immune reactions. AB - Liposomes have been recognized as excellent drug delivery systems, but when they come in direct contact with different blood components they may trigger an immediate activation of the innate immune system. The aim of the present study was to produce long-circulating, blood-compatible liposomes by developing a construct of liposomes covered by a novel unique heparin complex (CHC; 70 heparin molecules per complex) to avoid recognition by the innate immune system. Unilamellar, cationic liposomes were produced by hand extrusion through a 100-nm polycarbonate membrane. Coating of liposomes with the macromolecular CHC was accomplished by electrostatic interactions. Dynamic light scattering as well as QCM-D measurements were used to verify the electrostatic deposition of the negatively charged CHC to cationic liposomes. The CHC-coated liposomes did not aggregate when in contact with lepirudin anti-coagulated plasma. Unlike previous attempts to coat liposomes with heparin, this technique produced freely moveable heparin strands sticking out from the liposome surface, which exposed AT binding sites reflecting the anticoagulant potentials of the liposomes. In experiments using lepirudin-anticoagulated plasma, CHC-coated liposomes, in contrast to non coated control liposomes, did not activate the complement system, as evidenced by low C3a and sC5b-9 generation and reduced leakage from the liposomes. In conclusion, we show that liposomes can be successfully coated with the biopolymer CHC, resulting in biocompatible and stable liposomes that have significant application potential. PMID- 26897553 TI - Nervous system immunohistochemistry of the parasitic cnidarian Polypodium hydriforme at its free-living stage. AB - Polypodium hydriforme, the only species in Polypodiozoa, which is currently considered a class of Cnidaria, and likely a sister group to Medusozoa (together with Myxozoa), is a cnidarian adapted to intracellular parasitism inside sturgeon oocytes. Free-living P. hydriforme lives on river bottoms; it walks on supporting tentacles and uses sensory tentacles to capture food and bring it to the mouth. The nervous system of free-living P. hydriforme was studied by confocal microscopy and immunohistochemistry using antibodies to FMRF-amide and alpha tubulin combined with phalloidin-staining of F-actin fibres. A sensory FMRF-amide immunoreactive (IR) nerve net and an alpha-tubulin IR nerve net have been identified. The FMRF-amide IR nerve net underlies the epidermis along the tentacles and around the mouth; it consists of neurites emanating from epidermal sensory cells and basiepidermal ganglion cells, and it connects with cnidocytes. A deeper-lying alpha-tubulin IR nerve net occurs only in tentacles and looks like chains of different-sized beads crossing the mesoglea and entwining muscles. Anti alpha-tubulin staining also reveals microtubules in muscle cells following the longitudinal muscle fibres or the thin circular F-actin fibres of the tentacles. Cnidocytes in the tentacles are embedded in a regular hexagonal non-neural network formed by the tubulin IR cytoskeleton of epidermal cells. Cnidocils of the cnidocytes around the mouth and in walking tentacles are identical, but those in sensory tentacles differ in length and width. The possible homology of the tubulin IR nerve net with motor nerve nets of cnidarians is discussed. The absence of a classic nerve ring around the mouth and the lack of specialised sense organs are considered to be plesiomorphic characters for Cnidaria. PMID- 26897552 TI - Does familiarity affect the enjoyment of touchscreen games for people with dementia? AB - INTRODUCTION: Previous research has indicated that people living with dementia are able to use touchscreen technology, which presents an opportunity to deliver meaningful and engaging activities for people to pass the time independently. The challenge is to identify suitable applications from the thousands that are currently available, and familiarity, where an app is a digital version of an existing real world game, may be one solution. OBJECTIVES: To evaluate the concept of familiarity in gameplay with people living with dementia by comparing a known game with a novel game and measuring whether users are able to play these games independently and whether they enjoy doing so. METHODS: Thirty older adults living with dementia were recruited from local care services. Each participant was assigned to one of two groups. Group 1 played a familiar game (Solitaire) and Group 2 played a novel game (Bubble Xplode). Each participant played the same game on three separate occasions within one week. Number of gameplay attempts, whether a checkpoint was reached and how much time to reach the checkpoint were measured. A brief post-session interview was conducted to assess the participants' enjoyment. RESULTS: Ninety percent of participants attempted gameplay independently with 17% of participants in the familiar group reaching the checkpoint compared with 93% playing the novel game. Regardless of which game was played or whether the checkpoint was reached, 88% of all participants reported enjoyment of the gaming sessions. DISCUSSION: People living with dementia can play touchscreen games independently, but familiarity does not ensure successful gameplay. Enjoyment appears to be independent of progression through a game. The potential of novel and unfamiliar games as meaningful activities that people with dementia can engage with independently should be further explored. PMID- 26897554 TI - Sustainability of an in situ aided phytostabilisation on highly contaminated soils using fly ashes: Effects on the vertical distribution of physicochemical parameters and trace elements. AB - Aided phytostabilisation using trees and fly ashes is a promising technique which has shown its effectiveness in the management of highly metal-contaminated soils. However, this success is generally established based on topsoil physicochemical analysis and short-term experiments. This paper focuses on the long-term effects of the afforestation and two fly ashes (silico-aluminous and sulfo-calcic called FA1 and FA2, respectively) by assessing the integrity of fly ashes 10 years after their incorporation into the soil as well as the vertical distribution of the physicochemical parameters and trace elements (TEs) in the amended soils (F1 and F2) in comparison with a non-amended soil (R). Ten years after the soil treatment, the particle size distribution analysis between fly ashes and their corresponding masses (fly ash + soil particles) showed a loss or an agglomeration of finer particles. This evolution matches with the appearance of gypsum (CaSO4 2H2O) in FA2m instead of anhydrite (CaSO4), which is the major compound of FA2. This finding corresponds well with the dissolution and the lixiviation of Ca, S and P included in FA2 along the F2 soil profile, generating an accumulation of these elements at 30 cm depth. However, no variation of TE contamination was found between 0 and 25 cm depth in F2 soil except for Cd. Conversely, Cd, Pb, Zn and Hg enrichment was observed at 25 cm depth in the F1 soil, whereas no enrichment was observed for As. The fly ashes studied, and notably FA2, were able to reduce Cd, Pb and Zn availability in soil and this capacity persists over the time despite their structural and chemical changes. PMID- 26897555 TI - Early establishment response of different Pinus nigra ssp. salzmanii seed sources on contrasting environments: Implications for future reforestation programs and assisted population migration. AB - Forest restoration constitutes an important issue within adaptive environmental management for climate change at global scale. However, effective implementation of these programs can only be achieved by revising current seed transfer guidelines, as they lack inherent spatial and temporal dynamics associated with climate change. In this sense, provenance trials may provide key information on the relative performance of different populations and/or genotypes under changing ecological conditions. This study addresses a methodological approach to evaluate early plantation performance and the consequent phenotypic plasticity and the pattern of the adaptation of different seed sources in contrasting environments. To this end, six seed sources of Salzmann pine were tested at three contrasting trial sites testing a hypothetical assisted population migration. Adaptation at each site was assessed through Joint Regression and Additive Main effect and Multiplication Interaction (AMMI) models. Most of the observed variation was attributed to the environment (above 90% for all traits), even so genotype and genotype by environment interaction (GxE) were significant. Seedlings out-planted under better site conditions did not differ in survival but in height growth. However, on sites with higher constraints, survival differed among seed sources and diameter growth was high. The adaptation analyses (AMMI) indicated that the cold-continental seed source 'Soria' performed as a generalist seed source, whereas 'Cordilleras Beticas', the southernmost seed source, was more adapted to harsh environments (frost and drought) in terms of survival. The results supported partially the hypothesis that assisted migration of seed sources makes sense within limited transfer distances, and this was reinforced by the GxE results. The present study could be valuable to address adaptive transfer of seedings in ecological restoration and to determine the suitable seed sources for reforestation programs and assisted population migration under climatic changes. The reported results are based on 3 years' data and need to be considered in this context. PMID- 26897556 TI - Is undernutrition prognostic of infection complications in children undergoing surgery? A systematic review. AB - BACKGROUND: Healthcare-associated infections are costly and are increasingly viewed as an indicator of the quality of care. Although strategies to reduce infections have become widespread, few studies have formally investigated the role of undernutrition on the development of infection-related complications in children after surgery. AIM: To perform a systematic review of the literature to determine if undernutrition is prognostic of postoperative infection complications in children. METHODS: Electronic bibliographic and research databases were searched from 1950 to 2014. Inclusion criteria were studies in children (age <18 years) evaluating pre-operative nutritional status and reporting postoperative infection complications. Quality assessment was performed independently by two reviewers, with disagreements resolved by a third reviewer. The quality of the evidence was judged to be low in the majority of studies. FINDINGS: Ten cohort and two case-control studies met the inclusion criteria. Five studies reported an outcome combining infection-related complications, with the remainder reporting individual infection complications. Six studies reported surgical site infection (SSI) alone or in combination with other infection complications. Direct comparison between studies was difficult due to clinical and diagnostic heterogeneity. Unadjusted analyses (for patient or clinical variables) were suggestive of a relationship between undernutrition and infection complications. In studies controlling for other variables, the analyses did not remain significant for SSI. CONCLUSION: There was low-quality evidence that undernutrition may be predictive of postoperative infection complications in children, with the exception of SSI. However, inconsistencies in nutritional and outcome assessments made it difficult to draw conclusions. Larger, high-quality studies are warranted to further investigate a potential prognostic relationship. PMID- 26897557 TI - Successful control of an outbreak of GES-5 extended-spectrum beta-lactamase producing Pseudomonas aeruginosa in a long-term care facility in Japan. AB - BACKGROUND: Little is known about multidrug-resistant Pseudomonas aeruginosa (MDRP) outbreaks in long-term care facilities (LTCFs). AIM: To describe an MDRP outbreak in an LTCF and to clarify risk factors for MDRP acquisition. METHODS: Patients who were positive for MDRP at an LTCF from January 2013 to January 2014 were analysed. A descriptive analysis, a case-control study, and a microbiological analysis were performed. FINDINGS: A total of 23 MDRP cases were identified, 16 of which were confirmed in sputum samples. Healthcare workers were observed violating hand hygiene procedures when performing oral, wound, and genital care. Nasogastric tube and oxygen mask use was associated with MDRP acquisition in the respiratory tract, which might have been confounded by poor hand hygiene. Sharing unhygienic devices, such as portable oral suction devices for oral care, and washing bottles and ointments for wound and genital care with inadequate disinfection could explain the transmission of MDRP in some cases. Isolates from 11 patients were found to be indistinguishable or closely related by pulsed-field gel electrophoresis and harbouring the blaGES-5 gene. Subsequent enhanced infection control measures were supported by nearby hospitals and a local public health centre. No additional cases were identified for a year after the last case occurred in January 2014. CONCLUSION: An outbreak of MDRP with an antimicrobial resistance gene, blaGES-5, occurred in a Japanese LTCF. It was successfully controlled by enhanced infection control measures, which neighbouring hospitals and a local public health centre supported. PMID- 26897558 TI - Risk factors associated with domestic abuse directed at adults with disabilities in South Korea. AB - BACKGROUND: Most research on domestic abuse and disability has focused on women with disabilities, while research on abuse against men with disabilities and their risk factors is virtually non-existent. OBJECTIVE: The purpose of this research is to understand domestic abuse experienced by people with disabilities by investigating its prevalence and risk factors. METHOD: This research used the National Survey on Persons with Disabilities (2011). Using a stratified sampling method, 5259 respondents were identified to make up the final sample. Ordered logistic regression was used to verify risk factors for abuse. RESULTS: Risk factors for women with disabilities are age, educational attainment level, ADL, experiences of discrimination, awareness of disability discrimination, external support, and satisfaction with number of friends. Risk factors for men with disabilities are region, experiences of discrimination, awareness of disability discrimination, external support, and satisfaction with number of friends. For both women and men with disabilities, more experience of discrimination, greater awareness of disability discrimination, less external support, and less satisfaction with number of friends are associated with a higher likelihood of having experiences of abuse. Men with disabilities living in rural areas have a higher risk of abuse than those living in cities. Younger women, women with lower educational attainment, and those with lower physical functioning are more likely to have experienced abuse. CONCLUSIONS: Based on these findings, the authors make recommendations designed to protect people with disabilities from domestic abuse. PMID- 26897559 TI - Mesenchymal stromal cell-mediated neuroprotection and functional preservation of retinal ganglion cells in a rodent model of glaucoma. AB - BACKGROUND AIMS: Glaucoma is a leading cause of irreversible blindness involving loss of retinal ganglion cells (RGC). Mesenchymal stromal cells (MSC) have shown promise as a paracrine-mediated therapy for compromised neurons. It is, however, unknown whether dental pulp stem cells (DPSC) are effective as a cellular therapy in glaucoma and how their hypothesized influence compares with other more widely researched MSC sources. The present study aimed to compare the efficacy of adipose-derived stem cells, bone marrow-derived MSC (BMSC) and DPSC in preventing the loss of RGC and visual function when transplanted into the vitreous of glaucomatous rodent eyes. METHODS: Thirty-five days after raised intraocular pressure (IOP) and intravitreal stem cell transplantation, Brn3a(+) RGC numbers, retinal nerve fibre layer thickness (RNFL) and RGC function were evaluated by immunohistochemistry, optical coherence tomography and electroretinography, respectively. RESULTS: Control glaucomatous eyes that were sham-treated with heat killed DPSC had a significant loss of RGC numbers, RNFL thickness and function compared with intact eyes. BMSC and, to a greater extent, DPSC provided significant protection from RGC loss and RNFL thinning and preserved RGC function. DISCUSSION: The study supports the use of DPSC as a neuroprotective cellular therapy in retinal degenerative disease such as glaucoma. PMID- 26897561 TI - Preexcitation Syndromes. AB - The classic electrocardiogram in Wolff-Parkinson-White (WPW) syndrome is characterized by a short PR interval and prolonged QRS duration in the presence of sinus rhythm with initial slurring. The clinical syndrome associated with above electrocardiogram finding and the history of paroxysmal supraventricular tachycardia is referred to as Wolff-Parkinson-White syndrome. Various eponyms describing accessory or anomalous conduction pathways in addition to the normal pathway are collectively referred to as preexcitation syndromes. The latter form and associated eponyms are frequently used in literature despite controversy and disagreements over their actual anatomical existence and electrophysiological significance. This communication highlights inherent deficiencies in the knowledge that has existed since the use of such eponyms began. With the advent of curative ablation, initially surgical, and then catheter based, the knowledge gaps have been mostly filled with better delineation of the anatomic and electrophysiological properties of anomalous atrioventricular pathways. It seems reasonable, therefore, to revisit the clinical and electrophysiologic role of preexcitation syndromes in current practice. PMID- 26897562 TI - Conservative endoscopic management for pancreatic trauma. AB - Traumatic pancreatic injuries are rare: their severity correlates with main pancreatic duct involvement. We report the case of a 5-year-old child who presented with complete disruption of the main pancreatic duct, treated successfully with an endoscopically inserted double pigtail stent. PMID- 26897563 TI - Finely tunable fabrication and catalytic activity of gold multipod nanoparticles. AB - Gold multipod nanoparticles (Au Multipod NPs) containing multi-branches with sharp edges and tips were synthesized in high yield through a facile seed mediated method using cetyltrimethylammonium bromide (CTAB), Brij35, Au seed nanoparticles, Ag(+) ions, ascorbic acid, and sodium salicylate. The branch lengths of Au Multipod NPs were finely controlled by adjusting the molar ratio of mixed surfactants, and in particular by changing the amount of sodium salicylate. A formation mechanism for the star-shaped topologies was proposed and experimentally proved. The catalytic activity of the synthesized Au Multipod NPs was evaluated in ethanol electrooxidation reaction. The dependence of the catalytic performances on the nanostructural morphology was investigated. PMID- 26897564 TI - Oxidation of 2,4-dichlorophenol by non-radical mechanism using persulfate activated by Fe/S modified carbon nanotubes. AB - The aim of this study was to develop a new approach for the activation of persulfate (PS) based on carbon nanotubes (CNTs). Fe/S modified carbon nanotubes (Fe/S-CNTs) were synthesized via impregnation-precipitation in the aqueous-phase synthesis method. The morphologies and chemical states of the catalysts were characterized and 2,4-dichlorophenol (2,4-DCP) was selected to investigate the degradation performance using Fe/S-CNTs with PS. The results reveal that the Fe/S CNTs catalysts can significantly accelerate the removal of 2,4-DCP compared to single PS or PS/CNTs. The catalytic capacity is also enhanced by S modification and is affected by the solution pH. The iron loading content, PS concentration and catalyst dosage could play important roles in the degradation. A non-radical process of 2,4-DCP degradation is demonstrated for the first time in the results of the radical scavengers and chloride ionic, as well as persulfate decomposition. It is suggested that PS is first bonded with the sp(2)-hybridized system and activated by iron oxide particles and iron-sulfur complexes, then it reacts rapidly with the adsorbed 2,4-DCP. PMID- 26897565 TI - Nanoelectrical investigation and electrochemical performance of nickel oxide/carbon sphere hybrids through interface manipulation. AB - Advanced hetero-nanostructured materials for electrochemical devices, such as Li ion batteries (LiBs), dramatically depend on each functional component and their interfaces to transport and storage charges, where the bottleneck is the sluggish one in series. In this work, we prepare Ni(OH)2@C hybrids through a continuous feeding in reflux and followed by a hydrothermal treatment. The as-prepared Ni(OH)2@C can be further converted into NiO@C hybrids after thermal annealing. As a control, Ni(OH)2&C and NiO&C nanocomposites have also been prepared. Peakforce Tuna measurement shows the conductivity of the NiO@C hybrids is higher than that of NiO&C composites in nanoscale. To further investigate the quality of the interface, 100 charge/discharge cycles of the hybrids are performed in LiBs. The capacity retention of hybrid materials has significantly improved than the simple carbon composites. The enhancement of the electrochemical performance is attributed to the better electric conductivity and smaller charge transfer impedance and strong covalent interface between nickel species and carbon spheres obtained through the controlled seeded deposition. PMID- 26897566 TI - Metalloporphyrins immobilized in Fe3O4@SiO2 mesoporous submicrospheres: Reusable biomimetic catalysts for hydrocarbon oxidation. AB - We successfully immobilized metalloporphyrins (MeP) in mesoporous silica coating magnetite spheres. In this sense, we prepared two different classes of core@shell supports, which comprise aligned (Fe3O4-AM-MeP, MeP=FeP or MnP) and non-aligned (Fe3O4-NM-MeP, MeP=FeP or MnP) mesoporous magnetic structures. X-ray diffractometry and energy dispersive X-ray spectroscopy confirmed the mesoporous nature of the silica shell of the materials. Magnetization measurements, scanning and transmission electron microscopies (SEM/TEM), electrophoretic mobility (zeta potential), and infrared spectroscopy (FTIR) also confirm the composition and structure of the materials. The catalysts maintained their catalytic activity during nine reaction cycles toward hydrocarbon oxidation processes without detectable catalyst leaching. The catalysis results revealed a biomimetic pattern of cytochrome P450-type enzymes, thus confirming that the prepared materials are can effectively mimic the activity of such groups. PMID- 26897567 TI - Pd-grafted open metal site copper-benzene-1,4-dicarboxylate metal organic frameworks (Cu-BDC MOF's) as promising interfacial catalysts for sustainable Suzuki coupling. AB - In this work, open metal site metal-organic framework of Cu-BDC was selected as a support for the multi-step grafting of palladium. The palladium ions was coordinated onto the Schiff base-decorated Cu-BDC pore cage, that this bifunctional Pd@Cu-BDC/Py-SI catalyst was successfully applied for Suzuki cross coupling reaction. Recyclability test for the Pd@Cu-BDC/Py-SI catalyst showed a successful reusability for 7 runs. PMID- 26897568 TI - Fractional hereditariness of lipid membranes: Instabilities and linearized evolution. AB - In this work lipid ordering phase changes arising in planar membrane bilayers is investigated both accounting for elasticity alone and for effective viscoelastic response of such assemblies. The mechanical response of such membranes is studied by minimizing the Gibbs free energy which penalizes perturbations of the changes of areal stretch and their gradients only (Deseri and Zurlo, 2013). As material instabilities arise whenever areal stretches characterizing homogeneous configurations lie inside the spinoidal zone of the free energy density, bifurcations from such configurations are shown to occur as oscillatory perturbations of the in-plane displacement. Experimental observations (Espinosa et al., 2011) show a power-law in-plane viscous behavior of lipid structures allowing for an effective viscoelastic behavior of lipid membranes, which falls in the framework of Fractional Hereditariness. A suitable generalization of the variational principle invoked for the elasticity is applied in this case, and the corresponding Euler-Lagrange equation is found together with a set of boundary and initial conditions. Separation of variables allows for showing how Fractional Hereditariness owes bifurcated modes with a larger number of spatial oscillations than the corresponding elastic analog. Indeed, the available range of areal stresses for material instabilities is found to increase with respect to the purely elastic case. Nevertheless, the time evolution of the perturbations solving the Euler-Lagrange equation above exhibits time-decay and the large number of spatial oscillation slowly relaxes, thereby keeping the features of a long-tail type time-response. PMID- 26897569 TI - Comparative characterization of sewage sludge compost and soil: Heavy metal leaching characteristics. AB - The leaching and accumulation of heavy metals are major concerns following the land application of sewage sludge compost (SSC). We comparatively characterized SSC, the reference soil, and the SSC amended soil to investigate their similarities and differences regarding heavy metal leaching behavior and then to evaluate the effect of SSC land application on the leaching behavior of soil. Results showed that organic matter, including both of particulate organic matter (POM) and dissolved organic matter (DOM), were critical factors influencing heavy metal leaching from both of SSC and the soil. When SSC was applied to soil at the application rate of 48t/ha, the increase of DOM content slightly enhanced heavy metal leaching from the amended soil over the applicable pH domain (6 cinder gel-beads > reeds > control, which was different from cinder gel-beads/reeds > reeds > cinder gel-beads > control of indeno(1,2,3-cd)pyrene. This result indicated that the functional mechanism to remove indeno(1,2,3-cd)pyrene with six benzene rings was different from that of pyrene. The synergistic effect of reeds and cinder gel-beads for indeno(1,2,3 cd)pyrene removal was weaker than that of pyrene. But the absorption and transformation of reeds with high efficiency were beneficial to indeno(1,2,3 cd)pyrene removal from wetlands. Additionally, microbial analysis with high throughput sequencing presented that Gammaproteobacteria were dominant PAH degrading groups in bioremediation with immobilized bacteria. This strategy can serve as a model system for the removal of more complex or structurally related organic compounds from contaminated sites. PMID- 26897586 TI - Occupational and demographic factors associated with drug use among female sex workers at the China-Myanmar border. AB - BACKGROUND: Within the last decade, the use of amphetamine type stimulants (ATS) has swelled in Myanmar. Regionally, female sex workers have reported turning to ATS for occupational reasons. In doing so, drug-using female sex workers (FSW) face compounded risks for HIV and other sexually transmitted infections (STI). Here, we examine the factors that impact FSW drug use in Muse, a town along the China-Myanmar border. METHODS: In 2012, 101 FSW were recruited from entertainment venues and brothels along the Myanmar-Chinese border. Participants participated in a self-administered behavioral survey covering demographics, drug use, sex work, and risk behaviors. Bivariate and regression analyses were conducted in SPSS. RESULTS: Thirty four percent of respondents indicated current drug use. ATS derivatives were the most commonly used drugs (87.5%) with injection drug use being nearly non-existent in the sample. Drug using FSWs were older, had engaged in sex work longer, had more Chinese clients, and were more likely to have a previous boyfriend who had used drugs. They were also 3.5 times more likely to report a STI. Client condom use, HIV testing rates, and familiarity with public health resources did not statistically differ by drug use status. CONCLUSION: More research is needed to examine how romantic and professional sexual relationships push-and-pull FSW into using drugs. Our results suggest that diverse safer sex strategies, beyond client condom use, should be promoted with drug using FSWs, including strategies that acknowledge the impact of ATS use. PMID- 26897587 TI - The influence of structure depth on image blurring of micrometres-thick specimens in MeV transmission electron imaging. AB - This study investigates the influence of structure depth on image blurring of micrometres-thick films by experiment and simulation with a conventional transmission electron microscope (TEM). First, ultra-high-voltage electron microscope (ultra-HVEM) images of nanometer gold particles embedded in thick epoxy-resin films were acquired in the experiment and compared with simulated images. Then, variations of image blurring of gold particles at different depths were evaluated by calculating the particle diameter. The results showed that with a decrease in depth, image blurring increased. This depth-related property was more apparent for thicker specimens. Fortunately, larger particle depth involves less image blurring, even for a 10-MUm-thick epoxy-resin film. The quality dependence on depth of a 3D reconstruction of particle structures in thick specimens was revealed by electron tomography. The evolution of image blurring with structure depth is determined mainly by multiple elastic scattering effects. Thick specimens of heavier materials produced more blurring due to a larger lateral spread of electrons after scattering from the structure. Nevertheless, increasing electron energy to 2MeV can reduce blurring and produce an acceptable image quality for thick specimens in the TEM. PMID- 26897589 TI - Rock porosity quantification by dual-energy X-ray computed microtomography. AB - Porous media investigation by X-ray microtomography allows obtaining valuable quantitative and qualitative information, while preserving sample integrity. Modern X-ray nanotomography or Synchrotron radiation systems may distinguish structures sized only hundreds of nanometers. However, pores sized less than a few microns (microporosity) may be undetectable due to the system's spatial resolution and noise in microfocus sources, compromising the quality of the measurement. In this study a dual-energy methodology was developed to generate density-based images from two scans made at two different voltages (80kV and 130KV) with a microfocus bench-top microtomography system. The images obtained were quantized in 256 gray levels, where the lowest value (zero) corresponded to voids and the highest value (255) corresponded to the densest regions mapped. From density images and single energy images, porosity was evaluated and compared. Results indicate that density images present better results than single energy images when both are compared with porosity obtained by the helium injection method. In addition, images acquired in dual-energy show good agreement with the sample's real density values. PMID- 26897588 TI - Trichobilharzia regenti (Schistosomatidae): 3D imaging techniques in characterization of larval migration through the CNS of vertebrates. AB - Migration of parasitic worms through the host tissues, which may occasionally result in fatal damage to the internal organs, represents one of the major risks associated with helminthoses. In order to track the parasites, traditionally used 2D imaging techniques such as histology or squash preparation do not always provide sufficient data to describe worm location/behavior in the host. On the other hand, 3D imaging methods are widely used in cell biology, medical radiology, osteology or cancer research, but their use in parasitological research is currently occasional. Thus, we aimed at the evaluation of suitability of selected 3D methods to monitor migration of the neuropathogenic avian schistosome Trichobilharzia regenti in extracted spinal cord of experimental vertebrate hosts. All investigated methods, two of them based on tracking of fluorescently stained larvae with or without previous chemical clearing of tissue and one based on X-ray micro-CT, exhibit certain limits for in vivo observation. Nevertheless, our study shows that the tested methods as ultramicroscopy (used for the first time in parasitology) and micro-CT represent promising tool for precise analyzing of parasite larvae in the CNS. Synthesis of these 3D imaging techniques can provide more comprehensive look at the course of infection, host immune response and pathology caused by migrating parasites within entire tissue samples, which would not be possible with traditional approaches. PMID- 26897590 TI - Seafloor massive sulfide deposits support unique megafaunal assemblages: Implications for seabed mining and conservation. AB - Mining of seafloor massive sulfides (SMS) is imminent, but the ecology of assemblages at SMS deposits is poorly known. Proposed conservation strategies include protected areas to preserve biodiversity at risk from mining impacts. Determining site suitability requires biological characterisation of the mine site and protected area(s). Video survey of a proposed mine site and protected area off New Zealand revealed unique megafaunal assemblages at the mine site. Significant relationships were identified between assemblage structure and environmental conditions, including hydrothermal features. Unique assemblages occurred at both active and inactive chimneys and are particularly at risk from mining-related impacts. The occurrence of unique assemblages at the mine site suggests that the proposed protected area is insufficient alone and should instead form part of a network. These results provide support for including hydrothermally active and inactive features within networks of protected areas and emphasise the need for quantitative survey data of proposed sites. PMID- 26897591 TI - Sarcopenia as a Risk Factor for Cognitive Deterioration in Community-Dwelling Older Adults: A 1-Year Prospective Study. AB - OBJECTIVE: The purpose of this 1-year prospective study was to determine whether sarcopenia is an independent risk factor of cognitive deterioration in community dwelling older adults. STUDY DESIGN: One-year prospective study. SETTING: Japanese community. PARTICIPANTS: A total of 131 community-dwelling older adults aged 65 years and older participated in this study. MEASUREMENTS: We defined sarcopenia using the diagnostic algorithm recommended by the Asian Working Group for Sarcopenia, and the participants were classified into the sarcopenia and normal groups according to this definition. The participants' cognitive functions were assessed using the Mini-Mental State Examination (MMSE) during pre- and postdata collection (after 1 year). RESULTS: The rate of change in pre- and post MMSE scores during the follow-up term was significantly different between the 2 groups (normal group, -0.32 +/- 8.39%; sarcopenia group, -5.86 +/- 5.16%; P = .002). The analysis of covariance, adjusted for demographic data and the pre-MMSE scores, showed a significant change in the MMSE scores between the normal and sarcopenia group (F = 9.30, P = .003). Furthermore, in the multivariate logistic regression analysis, the cognitive function was significantly more likely to deteriorate (defined as a loss of at least 2 points of MMSE) in the sarcopenia group during the follow-up term (odds ratio: 7.86, 95% confidence interval: 1.53 40.5). CONCLUSIONS: Sarcopenia was identified as an independent risk factor of cognitive deterioration in community-dwelling older adults during the 1-year study period. PMID- 26897585 TI - The impact of ADHD persistence, recent cannabis use, and age of regular cannabis use onset on subcortical volume and cortical thickness in young adults. AB - BACKGROUND: Both Attention Deficit Hyperactivity Disorder (ADHD) and chronic cannabis (CAN) use have been associated with brain structural abnormalities, although little is known about the effects of both in young adults. METHODS: Participants included: those with a childhood diagnosis of ADHD who were CAN users (ADHD_CAN; n=37) and non-users (NU) (ADHD_NU; n=44) and a local normative comparison group (LNCG) who did (LNCG_CAN; n=18) and did not (LNCG_NU; n=21) use CAN regularly. Multiple regressions and MANCOVAs were used to examine the independent and interactive effects of a childhood ADHD diagnosis and CAN group status and age of onset (CUO) on subcortical volumes and cortical thickness. RESULTS: After controlling for age, gender, total brain volume, nicotine use, and past-year binge drinking, childhood ADHD diagnosis did not predict brain structure; however, persistence of ADHD was associated with smaller left precentral/postcentral cortical thickness. Compared to all non-users, CAN users had decreased cortical thickness in right hemisphere superior frontal sulcus, anterior cingulate, and isthmus of cingulate gyrus regions and left hemisphere superior frontal sulcus and precentral gyrus regions. Early cannabis use age of onset (CUO) in those with ADHD predicted greater right hemisphere superior frontal and postcentral cortical thickness. DISCUSSION: Young adults with persistent ADHD demonstrated brain structure abnormalities in regions underlying motor control, working memory and inhibitory control. Further, CAN use was linked with abnormal brain structure in regions with high concentrations of cannabinoid receptors. Additional large-scale longitudinal studies are needed to clarify how substance use impacts neurodevelopment in youth with and without ADHD. PMID- 26897593 TI - Stimulation of cortical bone formation with thienopyrimidine based inhibitors of Notum Pectinacetylesterase. AB - A group of small molecule thienopyrimidine inhibitors of Notum Pectinacetylesterase are described. We explored both 2-((5,6-thieno[2,3 d]pyrimidin-4-yl)thio)acetic acids and 2-((6,7-thieno[3,2-d]pyrimidin-4 yl)thio)acetic acids. In both series, highly potent, orally active Notum Pectinacetylesterase inhibitors were identified. PMID- 26897592 TI - Pain Management Algorithms for Implementing Best Practices in Nursing Homes: Results of a Randomized Controlled Trial. AB - OBJECTIVE: To enhance pain practices in nursing homes (NHs) using pain assessment and management algorithms and intense diffusion strategies. DESIGN: A cluster, randomized controlled trial. The intervention consisted of intensive training and support for the use of recommended pain assessment and management practices using algorithms (ALGs). Control facilities received pain education (EDU) only. SETTING: Twenty-seven NHs in the greater Puget Sound area participated. Facilities were diverse in terms of size, quality, and ownership. PARTICIPANTS: Data were collected from 485 NH residents; 259 for the intervention and 226 for the control group. MEASUREMENTS: Resident outcomes were nursing assistant (proxy) report and self-reported resident pain intensity. Process outcomes were adherence to recommended pain practices. Outcomes were measured at baseline, completion of the intervention (ALG) or training (EDU), and again 6 months later. RESULTS: Among 8 comparisons of outcome measures between ALG and EDU (changes in 4 primary pain measures compared at 2 postintervention time points) there was only 1 statistically significant but small treatment difference in proxy- or self reported pain intensity. Resident-reported worst pain decreased by an average of 0.8 points from baseline to 6 months among the EDU group and increased by 0.2 points among the ALG (P = .005), a clinically nonsignificant difference. There were no statistically significant differences in adherence to clinical guideline practice recommendations between ALG and EDU following the intervention. CONCLUSIONS: Future research needs to identify and test effective implementation methods for changing complex clinical practices in NHs, including those to reduce pain. PMID- 26897594 TI - A second-generation ferrocene-iminosugar hybrid with improved fucosidase binding properties. AB - The synthesis and the biological evaluation of a new ferrocenyl-iminosugar conjugate designed for fucosidase inhibitory and anticancer activity is described. The compound showed strong affinity for fucosidase from bovine kidney (Ki=23 nM) and from Bacteroides thetaiotaomicron (Ki=150 nM), displaying a 10 fold tighter binding affinity for these enzymes than the previous analogs. The interaction pattern that improves binding has been evaluated through structural analysis of the inhibitor-enzyme complex. The ferrocenyl-iminosugar exhibits significant anticancer activity on MDA-MB-231 and SK-MEL28 cell lines at 100 MUM. PMID- 26897595 TI - Meganuclease-Mediated COL7A1 Gene Correction for Recessive Dystrophic Epidermolysis Bullosa. PMID- 26897596 TI - The solid state of rebamipide: preparation, characterization, and dissolution. AB - Rebamipide is marketed as a peptic ulcer agent under the trade name Mucosta(R). The objective of this work was to investigate the existence of polymorphs and pseudopolymorphs of rebamipide. Two crystal forms of rebamipide were isolated by recrystallization and characterized by differential thermal analysis (DTA), thermogravimetric analysis (TG), powder X-ray diffractometry, infrared spectrometry, and nuclear magnetic resonance. The DTA curve of Form 1 showed one endothermic peak at 305.2 degrees C, and that of Form 2 showed one endothermic peak at 307.3 degrees C. The TG curve of Form 1 showed a single weight loss at 305.2 degrees C, which corresponded to melting. The TG curve of Form 2 also showed a single weight loss at 307.3 degrees C, which corresponded to melting. The melting point of Form 2 was higher than that of Form 1. In the dissolution studies in pH 6.8 buffer at 37 +/- 0.5 degrees C, the two crystal forms showed no significant differences in dissolution. After 3 months of storage at 0, 52, and 95% RH, the two crystal forms were not transformed. After milling with a Specamill for 2 h, the two crystal forms were not transformed. PMID- 26897599 TI - Dermal sheath cells contribute to postnatal hair follicle growth and cycling. PMID- 26897598 TI - The past and future of haemophilia: diagnosis, treatments, and its complications. AB - Haemophilia A and B are hereditary haemorrhagic disorders characterised by deficiency or dysfunction of coagulation protein factors VIII and IX, respectively. Recurrent joint and muscle bleeds lead to severe and progressive musculoskeletal damage. Existing treatment relies on replacement therapy with clotting factors, either at the time of bleeding (ie, on demand) or as part of a prophylactic schedule. The major complication of such therapy is the development of neutralising antibodies (ie, inhibitors), which is most frequent in haemophilia A. Treatment might improve considerably with the availability of new modified drugs, which might overcome existing prophylaxis limitations by reducing dosing frequency and thereby rendering therapy less distressing for the patient. Subcutaneous administration of some new therapies would also simplify prophylaxis in children with poor venous access. Gene therapy has the potential for a definitive cure, and important results have been obtained in haemophilia B. Despite improvements in haemophilia care, the availability of clotting factor concentrates for all affected individuals worldwide remains the biggest challenge. PMID- 26897600 TI - I'm gonna have to science the shit out of this: Comment on "Towards a Computational Comparative Neuroprimatology: Framing the language-ready brain" by Michael A. Arbib. PMID- 26897597 TI - Is There a Need for Early Seizure Prophylaxis After Traumatic Brain Injury? PMID- 26897601 TI - Using 3D Modeling Techniques to Enhance Teaching of Difficult Anatomical Concepts. AB - RATIONALE AND OBJECTIVES: Anatomy is an essential component of medical education as it is critical for the accurate diagnosis in organs and human systems. The mental representation of the shape and organization of different anatomical structures is a crucial step in the learning process. The purpose of this pilot study is to demonstrate the feasibility and benefits of developing innovative teaching modules for anatomy education of first-year medical students based on three-dimensional (3D) reconstructions from actual patient data. MATERIALS AND METHODS: A total of 196 models of anatomical structures from 16 anonymized computed tomography datasets were generated using the 3D Slicer open-source software platform. The models focused on three anatomical areas: the mediastinum, the upper abdomen, and the pelvis. Online optional quizzes were offered to first year medical students to assess their comprehension in the areas of interest. Specific tasks were designed for students to complete using the 3D models. RESULTS: Scores of the quizzes confirmed a lack of understanding of 3D spatial relationships of anatomical structures despite standard instruction including dissection. Written task material and qualitative review by students suggested that interaction with 3D models led to a better understanding of the shape and spatial relationships among structures, and helped illustrate anatomical variations from one body to another. CONCLUSIONS: The study demonstrates the feasibility of one possible approach to the generation of 3D models of the anatomy from actual patient data. The educational materials developed have the potential to supplement the teaching of complex anatomical regions and help demonstrate the anatomical variation among patients. PMID- 26897602 TI - Dual-energy CT Aortography with 50% Reduced Iodine Dose Versus Single-energy CT Aortography with Standard Iodine Dose. AB - RATIONALE AND OBJECTIVES: Because many patients with aortic pathology also have compromised renal function, we wished to investigate dual-energy computed tomography (DECT) aortography with 50% reduced iodine dose compared to single energy computed tomography (SECT) aortography with standard iodine dose. MATERIALS AND METHODS: Fifty patients had DECT aortography with 50% reduced iodine dose. Thirty-four of these patients had prior SECT aortography with standard iodine dose. DECT images were reconstructed at both 50 and 77 keV and were compared to SECT 120 kVp images. Reviewers measured aortic attenuation, image noise, and scored vascular enhancement. Signal-to-noise ratios (SNR) and contrast-to-noise ratios (CNR) were calculated. Volume CT dose index was recorded. RESULTS: Mean iodine dose was 47 g for SECT and 24 g for DECT. Aortic attenuation was highest at reduced iodine dose DECT 50 keV (570 +/- 105 Hounsfield units [HU]) compared to 77 keV (239 +/- 40 HU) or to standard iodine dose SECT 120 kVp (356 +/- 69 HU) (P < 0.05). Image noise was greatest at 50 keV compared to 77 keV and 120 kVp (P < 0.05) but was similar between 77 keV and 120 kVp (P > 0.05). SNR and CNR were the same at 50 keV and 120 kVp (P > 0.05). Mean vascular enhancement scores were all above 3.0 (good, typical enhancement). Volume CT dose index was 11.7 mGy for DECT and 11.8 mGy for SECT (P = 0.37). CONCLUSIONS: DECT aortography with 50% reduced iodine reconstructed at 50 keV resulted in significantly greater aortic attenuation, good subjective vascular enhancement, and comparable SNR and CNR compared to standard iodine dose SECT. DECT image noise at 77 keV was similar to SECT at 120 kVp. PMID- 26897603 TI - Locoregional Parotid Reconstruction. AB - Parotidectomy for benign and malignant tumors often results in conspicuous contour abnormalities and soft tissue defects. Immediate reconstruction leads to improved patient satisfaction and local or regional flaps can be used for reconstruction in most cases. This article provides a systematic approach to parotid reconstruction. PMID- 26897605 TI - An exotic invasive plant selects for increased competitive tolerance, but not competitive suppression, in a native grass. AB - Exotic invasive plants can exert strong selective pressure for increased competitive ability in native plants. There are two fundamental components of competitive ability: suppression and tolerance, and the current paradigm that these components have equal influences on a species' overall competitive ability has been recently questioned. If these components do not have equal influences on overall ability, then selection on competitive tolerance and suppression may be disproportionate. We used naturally invaded communities to study the effects of selection caused by an invasive forb, Centaurea stoebe, on a native grass, Pseudoroegneria spicata. P. spicata plants were harvested from within dense C. stoebe patches and from nearby uninvaded areas, divided clonally into replicates, then transplanted into a common garden where they grew alone or competed with C. stoebe. We found that P. spicata plants collected from within C. stoebe patches were significantly more tolerant of competition with C. stoebe than P. spicata plants collected from uninvaded areas, but plants from inside invaded patches were not superior at suppressing C. stoebe. These results are consistent with the hypothesis that strong competitors may select for tolerance to competition more than for the ability to suppress neighbors. This has important implications for how native plant communities may respond to invasion over time, and how invasive and native species may ultimately coexist. PMID- 26897604 TI - Trait-based plant ecology: moving towards a unifying species coexistence theory : Features of the Special Section. AB - Functional traits are the center of recent attempts to unify key ecological theories on species coexistence and assembling in populations and communities. While the plethora of studies on the role of functional traits to explain patterns and dynamics of communities has rendered a complex picture due to the idiosyncrasies of each study system and approach, there is increasing evidence on their actual relevance when aspects such as different spatial scales, intraspecific variability and demography are considered. PMID- 26897606 TI - Microdissection of lampbrush chromosomes as an approach for generation of locus specific FISH-probes and samples for high-throughput sequencing. AB - BACKGROUND: Over the past two decades, chromosome microdissection has been widely used in diagnostics and research enabling analysis of chromosomes and their regions through probe generation and establishing of chromosome- and chromosome region-specific DNA libraries. However, relatively small physical size of mitotic chromosomes limited the use of the conventional chromosome microdissection for investigation of tiny chromosomal regions. RESULTS: In the present study, we developed a workflow for mechanical microdissection of giant transcriptionally active lampbrush chromosomes followed by the preparation of whole-chromosome and locus-specific fluorescent in situ hybridization (FISH)-probes and high throughput sequencing. In particular, chicken (Gallus g. domesticus) lampbrush chromosome regions as small as single chromomeres, individual lateral loops and marker structures were successfully microdissected. The dissected fragments were mapped with high resolution to target regions of the corresponding lampbrush chromosomes. For investigation of RNA-content of lampbrush chromosome structures, samples retrieved by microdissection were subjected to reverse transcription. Using high-throughput sequencing, the isolated regions were successfully assigned to chicken genome coordinates. As a result, we defined precisely the loci for marker structures formation on chicken lampbrush chromosomes 2 and 3. Additionally, our data suggest that large DAPI-positive chromomeres of chicken lampbrush chromosome arms are characterized by low gene density and high repeat content. CONCLUSIONS: The developed technical approach allows to obtain DNA and RNA samples from particular lampbrush chromosome loci, to define precisely the genomic position, extent and sequence content of the dissected regions. The data obtained demonstrate that lampbrush chromosome microdissection provides a unique opportunity to correlate a particular transcriptional domain or a cytological structure with a known DNA sequence. This approach offers great prospects for detailed exploration of functionally significant chromosomal regions. PMID- 26897607 TI - Narrow band imaging endoscopy of the nasopharynx is not more useful than white light endoscopy for suspected nasopharyngeal carcinoma. AB - Endoscopy is often used to screen for nasopharyngeal carcinoma. A normal nasopharynx on white light endoscopy may yet harbor subclinical or occult malignancy. This study assessed whether the vascular pattern seen on narrow band imaging endoscopy could indicate this and thus be useful for detecting suspected nasopharyngeal carcinoma. The nasopharynx of 156 patients who failed serological screening for or presented with symptoms of nasopharyngeal carcinoma was graded under white light and narrow band imaging endoscopy and a biopsy taken. The accuracy of assessing the nasopharynx as being probably or definitely malignant on white light endoscopy was high (area under the curve = 0.924), as it was of being normal on narrow band imaging endoscopy (=0.799). The sensitivity and specificity of white light and narrow band imaging endoscopy for nasopharyngeal carcinoma was 93 and 22 %, and 92 and 98 %, respectively. Significantly associated with nasopharyngeal carcinoma was a high index of suspicion or definitely malignant grade on white light endoscopy (p < 0.0005, odds 58.978) and vascular tufts on narrow band imaging endoscopy (p = 0.020, odds 41.210). Narrow band imaging endoscopy of vasculature alone for suspected nasopharyngeal carcinoma is not more useful than white light endoscopy of nasopharyngeal morphology, nor does it add to or surpass the diagnostic accuracy of white light endoscopy in this regard. PMID- 26897608 TI - Detection of light and vibration modulates bioluminescence intensity in the glowworm, Arachnocampa flava. AB - Glowworms are larval fungus gnats that emit light from a specialised abdominal light organ. The light attracts small arthropod prey to their web-like silk snares. Larvae glow throughout the night and can modulate their bioluminescence in response to sensory input. To better understand light output regulation and its ecological significance, we examined the larvae's reaction to light exposure, vibration and sound. Exposure to a 5-min light pulse in the laboratory causes larvae to exponentially decrease their light output over 5-10 min until they completely switch off. They gradually return to pre-exposure levels but do not show a rebound. Larvae are most sensitive to ultraviolet light, then blue, green and red. Vibration of the larval snares results in a several-fold increase in bioluminescence over 20-30 s, followed by an exponential return to pre-exposure levels over 15-30 min. Under some conditions, larvae can respond to vibration by initiating bioluminescence when they are not glowing; however, the response is reduced compared to when they are glowing. We propose that inhibitory and excitatory mechanisms combine to modulate bioluminescence intensity by regulating biochemical reactions or gating the access of air to the light organ. PMID- 26897609 TI - Adolescents' smoking experiences, family structure, parental smoking and socio economic status in Ciudad Juarez, Mexico. AB - BACKGROUND: Cigarette smoking is the leading cause of preventable death worldwide. Tobacco use and secondhand-tobacco smoke (SHS) exposure are classified as a pediatric disease. In Mexico, the prevalence of smoking has decreased among adults but paradoxically increased among adolescents, particularly among young females. This study was designed to determine the association between adolescents' smoking experiences (smoking behaviors and second hand smoke [SHS] exposure), family structure, parental smoking and socio-economic status (SES) in Ciudad Juarez, Mexico. METHODS: This is a cross-sectional, population-based study. Data was collected from sixth-grade students (N = 506) attending school in Ciudad Juarez, Mexico. Descriptive analyses were conducted. The relationship between key outcome variables (adolescents smoking and SHS exposure) and independent variables (family structure, parental smoking, and SES level) were examined. Adjusted odds ratios were calculated. Multiple logistic regression analysis was performed while controlling for possible confounders (i.e. gender and age). RESULTS: The overall prevalence of ever/lifetime smoking and SHS exposure at home was 29.6 and 41.1 %, respectively. Results of the logistic regression analysis show that being a member of a non-intact family [(OR = 2.20; 95 % CI = 1.21-3.90) and (OR = 2.45; 95 % CI = 1.19-4.10) respectively], having parents who smoke [(OR = 4.41; 95 % CI = 2.15-5.46) and (OR = 4.95; 95 % CI = 2.25-7.12) respectively], and living in low SES setting [(OR = 1.73; 95 % CI = 1.43-3.30) and (OR = 1.99; 95 % CI = 1.16-4.00) respectively] are significantly associated with ever smoking and SHS exposure at home among sixth grade students. CONCLUSIONS: The findings of our study show that tobacco use and SHS exposure are strongly associated with adolescents living in low SES, non-intact households that have parents that smoke. To be effective, tobacco strategies specifically tailored for this particularly vulnerable group of adolescents would require a comprehensive, multi-faceted approach centered on prevention, cessation and protection. PMID- 26897612 TI - Estimating mercury emissions resulting from wildfire in forests of the Western United States. AB - Understanding the emissions of mercury (Hg) from wildfires is important for quantifying the global atmospheric Hg sources. Emissions of Hg from soils resulting from wildfires in the Western United States was estimated for the 2000 to 2013 period, and the potential emission of Hg from forest soils was assessed as a function of forest type and soil-heating. Wildfire released an annual average of 3100+/-1900kg-Hgy(-1) for the years spanning 2000-2013 in the 11 states within the study area. This estimate is nearly 5-fold lower than previous estimates for the study region. Lower emission estimates are attributed to an inclusion of fire severity within burn perimeters. Within reported wildfire perimeters, the average distribution of low, moderate, and high severity burns was 52, 29, and 19% of the total area, respectively. Review of literature data suggests that that low severity burning does not result in soil heating, moderate severity fire results in shallow soil heating, and high severity fire results in relatively deep soil heating (<5cm). Using this approach, emission factors for high severity burns ranged from 58 to 640MUg-Hgkg-fuel(-1). In contrast, low severity burns have emission factors that are estimated to be only 18-34MUg-Hgkg fuel(-1). In this estimate, wildfire is predicted to release 1-30gHgha(-1) from Western United States forest soils while above ground fuels are projected to contribute an additional 0.9 to 7.8gHgha(-1). Land cover types with low biomass (desert scrub) are projected to release less than 1gHgha(-1). Following soil sources, fuel source contributions to total Hg emissions generally followed the order of duff>wood>foliage>litter>branches. PMID- 26897611 TI - Unravelling organic matter and nutrient biogeochemistry in groundwater-fed rivers under baseflow conditions: Uncertainty in in situ high-frequency analysis. AB - In agricultural catchments, diffuse nutrient fluxes (mainly nitrogen N and phosphorus P), are observed to pollute receiving waters and cause eutrophication. Organic matter (OM) is important in mediating biogeochemical processes in freshwaters. Time series of the variation in nutrient and OM loads give insights into flux processes and their impact on biogeochemistry but are costly to maintain and challenging to analyse for elements that are highly reactive in the environment. We evaluated the capacity of the automated monitoring to capture typically low baseflow concentrations of the reactive forms of nutrients and OM: total reactive phosphorus (TRP), nitrate nitrogen (NO3-N) and tryptophan-like fluorescence (TLF). We compared the performance of in situ monitoring (wet chemistry analyser, UV-vis and fluorescence sensors) and automated grab sampling without instantaneous analysis using autosamplers. We found that automatic grab sampling shows storage transformations for TRP and TLF and do not reproduce the diurnal concentration pattern captured by the in situ analysers. The in situ TRP and fluorescence analysers respond to temperature variation and the relationship is concentration-dependent. Accurate detection of low P concentrations is particularly challenging due to large errors associated with both the in situ and autosampler measurements. Aquatic systems can be very sensitive to even low concentrations of P typical of baseflow conditions. Understanding transformations and measurement variability in reactive forms of nutrients and OM associated with in situ analysis is of great importance for understanding in-stream biogeochemical functioning and establishing robust monitoring protocols. PMID- 26897610 TI - A review of the environmental implications of in situ remediation by nanoscale zero valent iron (nZVI): Behavior, transport and impacts on microbial communities. AB - The increasing use of strategies incorporating nanoscale zero valent iron (nZVI) for soil and groundwater in situ remediation is raising some concerns regarding the potential adverse effects nZVI could have on indigenous microbial communities and ecosystem functioning. This review provides an overview of the current literature pertaining to the impacts of nZVI applications on microbial communities. Toxicity studies suggest that cell membrane disruption and oxidative stress through the generation of Fe(2+) and reactive oxygen species by nZVI are the main mechanisms contributing to nZVI cytotoxicity. In addition, nZVI has been shown to substantially alter the taxonomic and functional composition of indigenous microbial communities. However, because the physico-chemical conditions encountered in situ highly modulate nZVI toxicity, a better understanding of the environmental factors affecting nZVI toxicity and transport in the environment is of primary importance in evaluating the ecological consequences that could result from a more extensive use of nZVI. PMID- 26897613 TI - The unmet emotional, care/support, and informational needs of adult survivors of pediatric malignancies. AB - PURPOSE: This study describes the prevalence and predisposing factors for potentially modifiable unmet emotional, care/support, and information needs among adult survivors of childhood malignancies. METHODS: A randomly selected/stratified sample of participants in the Childhood Cancer Survivor Study (CCSS) responded to the CCSS-Needs Assessment Questionnaire (CCSS-NAQ) (n = 1189; mean [SD] current age, 39.7 [7.7], range = 26-61 years; 60.9 % women; mean [SD] years since diagnosis, 31.6 [4.7]). Survivors self-reported demographic information, health concerns, and needs; diagnosis/treatment data were obtained from medical records. Adjusted proportional risk ratios (prevalence ratios, PRs) were used to evaluate 77 separate needs. RESULTS: Fifty-four percent of survivors reported unmet psycho-emotional, 41 % coping, and 35 % care/support needs; 51, 35, and 33 %, respectively, reported unmet information needs related to cancer/treatment, the health care system, and surveillance. Female sex and annual income <$60K were associated with multiple needs; fewer needs were linked to diagnosis/years since/or age at diagnosis. Having moderate/extreme cancer-related anxiety/fear was associated with all needs, including a >6-fold increased prevalence for help dealing with "worry" (PR = 6.06; 95 % confidence interval [CI], 3.79-9.69) and anxiety (PR = 6.10; 95 % CI, 3.82-9.72) and a >5-fold increased prevalence for "needing to move on with life" (PR = 5.56; 95 % CI, 3.34 9.25) and dealing with "uncertainty about the future" (PR = 5.50; 95 % CI, 3.44 8.77). Radiation exposure and perceived health status were related to 42 and 29 needs, respectively. CONCLUSIONS: Demographic factors, disease/treatment characteristics, and intrapersonal factors can be used to profile survivors' unmet emotional, care/support, and information needs. IMPLICATIONS FOR CANCER SURVIVORS: These data can be used to enhance provider-survivor communication, identify at-risk subsamples, and appraise core intervention content. PMID- 26897616 TI - Editorial. PMID- 26897617 TI - Implementing business continuity management systems and sharing best practices at a European bank. AB - This paper provides an overview of the methodology applied by the Alpha Bank Group in order to implement a business continuity management (BCM) programme to its parent company (Alpha Bank SA), as well as to its subsidiaries in Albania, Bulgaria, Cyprus, Former Yugoslav Republic of Macedonia, Greece, Romania, Serbia, UK and Ukraine. It also reviews the problems faced, how they were overcome and the lessons learned. When implementing a BCM programme in a large organisation, it is very important to follow the methodology described by BCM standard ISO 22301, otherwise the business continuity plan is unlikely to work efficiently or comply with the business recovery requirements, as well as with the requirements of other interested parties, such as customers, regulatory authorities, vendors, service providers, critical associates, etc. PMID- 26897618 TI - Building public confidence in emergency management. AB - Over the years the State of Victoria has suffered many disasters, some of them resulting in extensive community, economic and environmental loss. A number of significant events, including the 2009 Victorian bushfires, major flood events in 2010-11 and their subsequent inquiries have resulted in the biggest overhaul of Victoria's emergency management arrangements since 1983. One significant element of the new arrangements is the inclusion of an entity whose role it is to assure the emergency management arrangements at the system level--the first time such a role has existed. This paper will describe the reform programme currently underway in Victoria, as well as the governance and structural arrangements that have been put in place, before detailing the assurance processes that are being implemented. PMID- 26897614 TI - Readiness to change is a predictor of reduced substance use involvement: findings from a randomized controlled trial of patients attending South African emergency departments. AB - BACKGROUND: This study examines whether readiness to change is a predictor of substance use outcomes and explores factors associated with RTC substance use among patients at South African emergency departments. METHODS: We use data from participants enrolled into a randomized controlled trial of a brief substance use intervention conducted in three emergency departments in Cape Town, South Africa. RESULTS: In adjusted analyses, the SOCRATES "Recognition" (B = 11.6; 95 % CI = 6.2-17.0) and "Taking Steps" score (B = -9.5; 95 % CI = -15.5- -3.5) as well as alcohol problems (B = 4.4; 95 % CI = 0.9-7.9) predicted change in substance use involvement at 3 month follow-up. Severity of depression (B = 0.2; 95 % CI = 0.1 0.3), methamphetamine use (B = 3.4; 95 % CI = 0.5- 6.3) and substance-related injury (B = 1.9; 95 % CI = 0.6-3.2) were associated with greater recognition of the need for change. Depression (B = 0.1; 95 % CI = 0.04 -0.1) and methamphetamine use (B = 2.3; 95 % CI = 0.1 -4.2) were also associated with more ambivalence about whether to change. Participants who presented with an injury that was preceded by substance use were less likely to be taking steps to reduce their substance use compared to individuals who did not (B = -1.7; 95 % CI = -5.0 -0.6). CONCLUSION: Findings suggest that brief interventions for this population should include a strong focus on building readiness to change substance use through motivational enhancement strategies. Findings also suggest that providing additional support to individuals with depression may enhance intervention outcomes. TRIAL REGISTRATION: This trial registered with the Pan African Clinical Trial Registry (PACTR201308000591418) on 14/07/2013. PMID- 26897619 TI - Airline business continuity and IT disaster recovery sites. AB - Business continuity is defined as the capability of the organisation to continue delivery of products or services at acceptable predefined levels following a disruptive incident. Business continuity is fast evolving to become a critical and strategic decision for any organisation. Transportation in general, and airlines in particular, is a unique sector with a specialised set of requirements, challenges and opportunities. Business continuity in the airline sector is a concept that is generally overlooked by the airline managements. This paper reviews different risks related to airline processes and will also propose solutions to these risks based on experiences and good industry practices. PMID- 26897615 TI - Phase II study of amrubicin (SM-5887), a synthetic 9-aminoanthracycline, as first line treatment in patients with metastatic or unresectable soft tissue sarcoma: durable response in myxoid liposarcoma with TLS-CHOP translocation. AB - PURPOSE: Amrubicin is a third generation synthetic 9-aminoanthracycline that specifically inhibits topoisomerase II. Amrubicin preferentially concentrates in tumor cells leading to tumor cell death without causing cardiac toxicity. This phase II multicenter study was done to evaluate the efficacy and tolerability of amrubicin in advanced soft tissue sarcoma (STS). PATIENTS AND METHODS: 24 eligible patients with chemotherapy-naive metastatic or unresectable STS were treated with amrubicin 40 mg/m(2) intravenously daily for three consecutive days in 21 days cycles with growth factor support. Patients continued to receive treatment, as long as it was tolerated, in the absence of significant disease progression. The disease was followed on imaging scans every 6 weeks. The primary endpoint of the study was the best overall response rate. RESULTS: The best overall response rate was 13% in 23 evaluable patients. Median progression-free survival was 5.8 months, and median overall survival was 26 months. Grade 3 to 4 toxicities of febrile neutropenia and anemia occurred in 21% of treated patients. One patient with metastatic myxoid liposarcoma with TLS-CHOP translocation had a durable response and received 40 cycles of amrubicin. There was no significant cardiac toxicity. CONCLUSIONS: Amrubicin has efficacy comparable to doxorubicin in adult STS, is well tolerated and has no significant cardiac toxicity up to a cumulative dose of 4800 mg /m(2). Topoisomerase II inhibition with amrubicin warrants further study as a potential 'targeted therapy' for TLS-CHOP translocated myxoid liposarcoma. Results from this trial favor the use of amrubicin for the treatment of STS. PMID- 26897620 TI - Mission possible: Building an effective business continuity team in seven steps. AB - Several books and studies exist on the creation, development and benefits of high performing teams; many others offer insights into the business continuity management (BCM) discipline, crisis response and planning. Very rarely, however, do they cover both. This paper will explore the seven main development areas that helped build the foundation for a successful and high-performing BCM team in the Australian Taxation Office. Practical, actionable advice will be provided, recognising that the task for those starting out can be quite daunting and complex. PMID- 26897621 TI - Operation Windshield and the simplification of emergency management. AB - Large, complex, multi-stakeholder exercises are the culmination of years of gradual progression through a comprehensive training and exercise programme. Exercises intended to validate training, refine procedures and test processes initially tested in isolation are combined to ensure seamless response and coordination during actual crises. The challenges of integrating timely and accurate situational awareness from an array of sources, including response agencies, municipal departments, partner agencies and the public, on an ever growing range of media platforms, increase information management complexity in emergencies. Considering that many municipal emergency operations centre roles are filled by staff whose day jobs have little to do with crisis management, there is a need to simplify emergency management and make it more intuitive. North Shore Emergency Management has accepted the challenge of making emergency management less onerous to occasional practitioners through a series of initiatives aimed to build competence and confidence by making processes easier to use as well as by introducing technical tools that can simplify processes and enhance efficiencies. These efforts culminated in the full-scale earthquake exercise, Operation Windshield, which preceded the 2015 Emergency Preparedness and Business Continuity Conference in Vancouver, British Columbia. PMID- 26897622 TI - The critical need for animal disaster response plans. AB - In the tragic aftermath of disasters over the past 30+ years, people have learned that disaster planning for individuals, for communities and for many businesses must include animals. This paper discusses why emergency planning for animals is a necessity for individuals and animal-focused businesses, as well as being a critical element in community disaster response strategies. Communication between affected groups and integration of disaster plans provide for a better response, which allows for a quicker recovery. Ensuring that animals are included in disaster mitigation/preparedness/response/ recovery plans increases resilience. It will provide a framework to manage personal and business preparedness and to launch animal disaster preparedness initiatives in communities. PMID- 26897623 TI - Considerations and benefits of implementing an online database tool for business continuity. AB - In today's challenging climate of ongoing fiscal restraints, limited resources and complex organisational structures there is an acute need to investigate opportunities to facilitate enhanced delivery of business continuity programmes while maintaining or increasing acceptable levels of service delivery. In 2013, Health Emergency Management British Columbia (HEMBC), responsible for emergency management and business continuity activities across British Columbia's health sector, transitioned its business continuity programme from a manual to automated process with the development of a customised online database, known as the Health Emergency Management Assessment Tool (HEMAT). Key benefits to date include a more efficient business continuity input process, immediate situational awareness for use in emergency response and/or advanced planning and streamlined analyses for generation of reports. PMID- 26897624 TI - Promoting a culture of disaster preparedness. AB - Disasters from all hazards, ranging from natural disasters, human-induced disasters, effects of climate change to social conflicts can significantly affect the healthcare system and community. This requires a paradigm shift from a reactive approach to a disaster risk management 'all-hazards' approach. Disaster management is a joint effort of the city, state, regional, national, multi agencies and international organisations that requires effective communication, collaboration and coordination. This paper offers lessons learned and best practices, which, when taken into consideration, can strengthen the phases of disaster risk management. PMID- 26897625 TI - Erratum to: A tribute to Dr. Raymond Read. PMID- 26897626 TI - Phenology of deer ked (Lipoptena cervi) host-seeking flight activity and its relationship with prevailing autumn weather. AB - BACKGROUND: The deer ked (Lipoptena cervi) is an ectoparasite on cervids that has invaded large parts of Norway, Sweden and Finland during recent decades. During their host-seeking flight activity, the adult deer keds constitute a considerable nuisance to people and limit human outdoor recreation. The bites of the deer ked can cause long-lasting dermatitis in humans. Determining the pattern of flight activity during autumn is hence important. METHODS: Data on flight phenology was gathered by walking along transects in the forest in two counties of Norway during 2009-2013, counting the number of host-seeking keds. We analysed how the flight activity of deer keds varied depending on date and prevailing weather during autumn. RESULTS: The best model of flight activity included both date and temperature, both as nonlinear terms. Host-seeking deer keds were observed from early August to mid-November with a marked peak in late September. Number of host seeking keds declined with temperatures falling below the mean, but did not increase much at above mean temperatures. The pattern of flight phenology was similar across the two counties and five years. CONCLUSIONS: Parasitic arthropods may be strongly affected by prevailing weather during off-host periods. Our study shows an estimated positive effect of temperature on deer ked flight activity mainly for below mean temperatures in late autumn, while the effect of temperature on flight activity in early autumn was weak. The pattern of host seeking flight activity during late, rather than early autumn, is hence more likely to change with ongoing climate change, with a predicted increase in duration of the host-seeking period. PMID- 26897627 TI - Validating and reliability testing the descriptive data and three different disease diagnoses of the internet-based DOGRISK questionnaire. AB - BACKGROUND: The DOGRISK questionnaire is an internet-based ongoing study of canine nutrition, living environment, and disease. Here we aim to assess the performance of the questionnaire using data from the first three years in relation to some descriptive and disease variables. We used associated questions, official register records, test-retest repeatability, and email/mail contact with questionnaire respondents. RESULTS: Reliability against an official register of gender, season of birth, breed, and results of hip radiography was tested and Cohen's Kappa was between 0.95-0.99. Internal consistencies of hypothyroidism status and dog's age were calculated using Cronbach's Alpha (alpha = 0.95 and alpha = 0.99, respectively). Test-retest repeatability of ten variables among 224 participants was analyzed. Gender, season of birth, and born in owner family had Cohen's Kappa > 0.86, color of coat, vaccination status as an adult, other dogs in household, and vaccination status as a puppy had Cohen's Kappa between 0.67 0.80, and body condition score under two months of age and tidiness of household, had Cohen's kappa of 0.45 and 0.42, respectively. In addition, time spent outside had Cohen's kappa of 0.37. Of the owners contacted by email/mail to confirm their dog's atopy/allergy (skin symptoms), 8.9% reported that they had given an incorrect answer (positive predicted value 91%), but only 69% of all reaffirmed positive answers had a diagnosis set by a veterinarian. CONCLUSIONS: Our study showed that owners were diligent with basic information and with the status of three diseases. Cohen's Kappa in the reliability of the test-retest was in most variables at least 0.67. We propose that the descriptive variables and the disease variables be used as such when we generate hypotheses from the DOGRISK data. PMID- 26897628 TI - Using synthetic biology to increase nitrogenase activity. AB - BACKGROUND: Nitrogen fixation has been established in protokaryotic model Escherichia coli by transferring a minimal nif gene cluster composed of 9 genes (nifB, nifH, nifD, nifK, nifE, nifN, nifX, hesA and nifV) from Paenibacillus sp. WLY78. However, the nitrogenase activity in the recombinant E. coli 78-7 is only 10 % of that observed in wild-type Paenibacillus. Thus, it is necessary to increase nitrogenase activity through synthetic biology. RESULTS: In order to increase nitrogenase activity in heterologous host, a total of 28 selected genes from Paenibacillus sp. WLY78 and Klebsiella oxytoca were placed under the control of Paenibacillus nif promoter in two different vectors and then they are separately or combinationally transferred to the recombinant E. coli 78-7. Our results demonstrate that Paenibacillus suf operon (Fe-S cluster assembly) and the potential electron transport genes pfoAB, fldA and fer can increase nitrogenase activity. Also, K. oxytoca nifSU (Fe-S cluster assembly) and nifFJ (electron transport specific for nitrogenase) can increase nitrogenase activity. Especially, the combined assembly of the potential Paenibacillus electron transporter genes (pfoABfldA) with K. oxytoca nifSU recovers 50.1 % of wild-type (Paenibacillus) activity. However, K. oxytoca nifWZM and nifQ can not increase activity. CONCLUSION: The combined assembly of the potential Paenibacillus electron transporter genes (pfoABfldA) with K. oxytoca nifSU recovers 50.1 % of wild-type (Paenibacillus) activity in the recombinant E. coli 78-7. Our results will provide valuable insights for the enhancement of nitrogenase activity in heterogeneous host and will provide guidance for engineering cereal plants with minimal nif genes. PMID- 26897629 TI - Early Adolescent Friendship Selection Based on Externalizing Behavior: the Moderating Role of Pubertal Development. The SNARE Study. AB - This study examined friendship (de-)selection processes in early adolescence. Pubertal development was examined as a potential moderator. It was expected that pubertal development would be associated with an increased tendency for adolescents to select their friends based on their similarities in externalizing behavior engagement (i.e., delinquency, alcohol use, and tobacco use). Data were used from the first three waves of the SNARE (Social Network Analysis of Risk behavior in Early adolescence) study (N = 1144; 50 % boys; M age = 12.7; SD = 0.47), including students who entered the first year of secondary school. The hypothesis was tested using Stochastic Actor-Based Modeling in SIENA. While taking the network structure into account, and controlling for peer influence effects, the results supported this hypothesis. Early adolescents with higher pubertal development were as likely as their peers to select friends based on similarity in externalizing behavior and especially likely to remain friends with peers who had a similar level of externalizing behavior, and thus break friendship ties with dissimilar friends in this respect. As early adolescents are actively engaged in reorganizing their social context, adolescents with a higher pubertal development are especially likely to lose friendships with peers who do not engage in externalizing behavior, thus losing an important source of adaptive social control (i.e., friends who do not engage in externalizing behavior). PMID- 26897630 TI - Impact of the condolence letter on the experience of bereaved families after a death in intensive care: study protocol for a randomized controlled trial. AB - BACKGROUND: As intensive care mortality is high, end of life is a subject of major concern for intensivists. In this context, relatives are particularly vulnerable and prone to post-ICU syndrome, in the form of high levels of anxiety, depression, post-traumatic stress, and complicated grief. Grieving families suffer from a feeling of abandonment and evoke the need to get back in touch with the team to ask questions and remove doubts, but very few actually do. Aiding families during the grieving process is an important aspect of palliative care. A condolence letter represents an opportunity to recognize the pain of the family member and the strong tie that linked the family member to the ICU team, and to offer additional information if necessary. The goal of the study is to measure the impact of the condolence letter on the experience of bereaved families after a death in the ICU. Our hypothesis is that a post-death follow-up in the form of a condolence letter sent by the ICU physician who was in charge of the patient may help to reduce the risks of presenting symptoms of anxiety/depression, post traumatic stress, and complicated grief. METHODS/DESIGN: This is a randomized, controlled, multicenter study. Research will compare two groups of bereaved family members: one group that does not receive a condolence letter (control) and one group that receives a condolence letter 15 days after the death (intervention). Each of the 22 participating centers will include 12 relatives. Participating relatives will be followed up by phone with a call at 1 month and one at 6 months to complete questionnaires, permitting evaluation of post-ICU burden. The main outcome is anxiety and depression measured at 1 month. Other outcomes include evaluation of quality of dying and death, post-traumatic stress, and complicated grief. DISCUSSION: This study will allow us to assess if sending a condolence letter can reduce the risks of presenting symptoms of anxiety and depression, complicated grief, and symptoms of post-traumatic stress disorder after the death of a loved one in the ICU. TRIAL REGISTRATION: CLINICAL TRIALS REGISTRATION NUMBER: Clinicaltrials.gov NCT02325297 (23 December 2014). PMID- 26897633 TI - Dental Stigmata of Congenital Syphilis: A Historic Review With Present Day Relevance. AB - Syphilis was the first sexually transmitted disease to be diagnosed in childhood. Most developed countries controlled syphilis effectively after the 1950s and congenital syphilis became rare. Since the late 1990s there has been a resurgence of syphilis in developed and developing countries and the WHO estimates that at least half a million infants die of congenital syphilis every year. The earliest reference to the dental manifestations of congenital syphilis was by Sir Jonathan Hutchinson, Assistant Surgeon at The London Hospital in 1861. Three main dental defects are described in congenital syphilis; Hutchinson's incisors, Moon's molars or bud molars, and Fournier's molars or mulberry molars. Although many physicians, dentists, and pathologists in developed countries will be aware of the dental features of syphilis, most will never have seen a case or made the diagnosis. The purpose of this article is to review some of the history of congenital syphilis, remind healthcare professionals of the features, and bring to their attention that the changes are still prevalent and that milder cases can be mistaken for other causes of hypoplasia. PMID- 26897631 TI - Identification of bovine sperm acrosomal proteins that interact with a 32-kDa acrosomal matrix protein. AB - Mammalian fertilization is accomplished by the interaction between sperm and egg. Previous studies from this laboratory have identified a stable acrosomal matrix assembly from the bovine sperm acrosome termed the outer acrosomal membrane matrix complex (OMC). This stable matrix assembly exhibits precise binding activity for acrosin and N-acetylglucosaminidase. A highly purified OMC fraction comprises three major (54, 50, and 45 kDa) and several minor (38-19 kDa) polypeptides. The set of minor polypeptides (38-19 kDa) termed "OMCrpf polypeptides" is selectively solubilized by high-pH extraction (pH 10.5), while the three major polypeptides (55, 50, and 45 kDa) remain insoluble. Proteomic identification of the OMC32 polypeptide (32 kDa polypeptide isolated from high-pH soluble fraction of OMC) yielded two peptides that matched the NCBI database sequence of acrosin-binding protein. Anti-OMC32 recognized an antigenically related family of polypeptides (OMCrpf polypeptides) in the 38-19-kDa range with isoelectric points ranging between 4.0 and 5.1. Other than glycohydrolases, OMC32 may also be complexed to other acrosomal proteins. The present study was undertaken to identify and localize the OMC32 binding polypeptides and to elucidate the potential role of the acrosomal protein complex in sperm function. OMC32 affinity chromatography of a detergent-soluble fraction of bovine cauda sperm acrosome followed by mass spectrometry-based identification of bound proteins identified acrosin, lactadherin, SPACA3, and IZUMO1. Co immunoprecipitation analysis also demonstrated the interaction of OMC32 with acrosin, lactadherin, SPACA3, and IZUMO1. Our immunofluorescence studies revealed the presence of SPACA3 and lactadherin over the apical segment, whereas IZUMO1 is localized over the equatorial segment of Triton X-100 permeabilized cauda sperm. Immunoblot analysis showed that a significant portion of SPACA3 was released after the lysophosphatidylcholine (LPC)-induced acrosome reaction, whereas the IZUMO1 and lactadherin polypeptides remain associated to the particulate fraction. Almost entire population of bovine sperm IZUMO1 relocates to the equatorial segment during the LPC-induced acrosome reaction. We propose that the interaction of OMC32 matrix polypeptide with detergent-soluble acrosomal proteins regulates the release of hydrolases/other acrosomal protein(s) during the acrosome reaction. PMID- 26897632 TI - L-Cysteine supplementation increases adiponectin synthesis and secretion, and GLUT4 and glucose utilization by upregulating disulfide bond A-like protein expression mediated by MCP-1 inhibition in 3T3-L1 adipocytes exposed to high glucose. AB - Adiponectin is an anti-diabetic and anti-atherogenic adipokine; its plasma levels are decreased in obesity, insulin resistance, and type 2 diabetes. An adiponectin interacting protein named disulfide bond A-like protein (DsbA-L) plays an important role in the assembly of adiponectin. This study examined the hypothesis that L-cysteine (LC) regulates glucose homeostasis through the DsbA-L upregulation and synthesis and secretion of adiponectin in diabetes. 3T3L1 adipocytes were treated with LC (250 and 500 uM, 2 h) and high glucose (HG, 25 mM, 20 h). Results showed that LC supplementation significantly (p < 0.05) upregulated the DsbA-L, adiponectin, and GLUT-4 protein expression and glucose utilization in HG-treated adipocytes. LC supplementation significantly (p < 0.05) promoted the secretion of total and HMW adiponectin secretion in HG-treated adipocytes. In addition, LC significantly (p < 0.05) decreased ROS production and MCP-1 secretion in HG-treated cells. We further investigated whether MCP-1 has any role of LC on DsbA-L expression and adiponectin levels in 3T3-L1 cells. Treatment with LC prevented the decrease in DsbA-L, adiponectin, and GLUT-4 expression in 3T3L1 adipocyte cells exposed to MCP-1. Thus, this study demonstrates that DsbA-L and adiponectin upregulation mediates the beneficial effects of LC on glucose utilization by inhibiting MCP-1 secretion in adipocytes and provides a novel mechanism by which LC supplementation can improve insulin sensitivity in diabetes. PMID- 26897634 TI - Medical Knowledge Assessment by Hematology and Medical Oncology In-Training Examinations Are Better Than Program Director Assessments at Predicting Subspecialty Certification Examination Performance. AB - The Accreditation Council for Graduate Medical Education's Next Accreditation System requires training programs to demonstrate that fellows are achieving competence in medical knowledge (MK), as part of a global assessment of clinical competency. Passing American Board of Internal Medicine (ABIM) certification examinations is recognized as a metric of MK competency. This study examines several in-training MK assessment approaches and their ability to predict performance on the ABIM Hematology or Medical Oncology Certification Examinations. Results of a Hematology In-Service Examination (ISE) and an Oncology In-Training Examination (ITE), program director (PD) ratings, demographic variables, United States Medical Licensing Examination (USMLE), and ABIM Internal Medicine (IM) Certification Examination were compared. Stepwise multiple regression and logistic regression analyses evaluated these assessment approaches as predictors of performance on the Hematology or Medical Oncology Certification Examinations. Hematology ISE scores were the strongest predictor of Hematology Certification Examination scores (beta = 0.41) (passing odds ratio [OR], 1.012; 95 % confidence interval [CI], 1.008-1.015), and the Oncology ITE scores were the strongest predictor of Medical Oncology Certification Examination scores (beta = 0.45) (passing OR, 1.013; 95 % CI, 1.011-1.016). PD rating of MK was the weakest predictor of Medical Oncology Certification Examination scores (beta = 0.07) and was not significantly predictive of Hematology Certification Examination scores. Hematology and Oncology ITEs are better predictors of certification examination performance than PD ratings of MK, reinforcing the effectiveness of ITEs for competency-based assessment of MK. PMID- 26897635 TI - Transcriptomic analyses identify association between mitotic kinases, PDZ-binding kinase and BUB1, and clinical outcome in breast cancer. AB - Protein kinases are important components in oncogenic transformation of breast cancer. Evaluation of upregulated genes that codify for protein kinases could be used as biomarkers to predict clinical outcome. Gene expression and functional analyses using public datasets were performed to identify differential gene expression and functions in basal-like tumors compared with normal breast tissue. Overall survival (OS) associated with upregulated genes was explored using the KM Plotter online tool. The prognostic influence of these genes in luminal tumors and systemically untreated patients was also assessed. Of the 426 transcripts identified in basal-like tumors, 11 genes that coded for components of protein kinases were upregulated with more than a fourfold change. Regulation of cell cycle was an enriched function containing 10 of these 11 identified genes. Among them, expression of four genes, BUB1beta, CDC28, NIMA, and PDZ binding kinase, were all associated with improved OS when using at least one probe in the basal like subtype. Two genes, BUB1beta and PDZ binding kinase, showed consistent association with improved OS irrespective of the gene probe used for the analysis. No association was observed for these genes with relapse-free survival. In contrast, both BUB1beta and PDZ binding kinase showed worse OS in luminal tumors and in a cohort of systemically untreated patients. BUB1beta and PDZ binding kinase are associated with improved OS in basal-like tumors and worse OS in luminal and untreated patients. The association with a better outcome in basal like tumors could be due to a more favorable response to chemotherapy. PMID- 26897636 TI - The involvement of protein kinase C-epsilon in isoflurane induced preconditioning of human embryonic stem cell--derived Nkx2.5(+) cardiac progenitor cells. AB - BACKGROUND: Anesthetic preconditioning can improve survival of cardiac progenitor cells exposed to oxidative stress. We investigated the role of protein kinase C and isoform protein kinase C-epsilon in isoflurane-induced preconditioning of cardiac progenitor cells exposed to oxidative stress. METHODS: Cardiac progenitor cells were obtained from undifferentiated human embryonic stem cells. Immunostaining with anti-Nkx2.5 was used to confirm the differentiated cardiac progenitor cells. Oxidative stress was induced by H2O2 and FeSO4. For anesthetic preconditioning, cardiac progenitor cells were exposed to 0.25, 0.5, and 1.0 mM of isoflurane. PMA and chelerythrine were used for protein kinase C activation and inhibition, while epsilonpsiRACK and epsilonV1-2 were used for protein kinase C -epsilon activation and inhibition, respectively. RESULTS: Isoflurane preconditioning decreased the death rate of Cardiac progenitor cells exposed to oxidative stress (death rates isoflurane 0.5 mM 12.7 +/- 9.3%, 1.0 mM 12.0 +/- 7.7% vs. control 31.4 +/- 10.2%). Inhibitors of both protein kinase C and protein kinase C -epsilon abolished the preconditioning effect of isoflurane 0.5 mM (death rates 27.6 +/- 13.5% and 25.9 +/- 8.7% respectively), and activators of both protein kinase C and protein kinase C - epsilon had protective effects from oxidative stress (death rates 16.0 +/- 3.2% and 10.6 +/- 3.8% respectively). CONCLUSIONS: Both PKC and PKC-epsilon are involved in isoflurane-induced preconditioning of human embryonic stem cells -derived Nkx2.5(+) Cardiac progenitor cells under oxidative stress. PMID- 26897637 TI - Meaningful traits for grouping plant species across arid ecosystems. AB - Grouping species may provide some degree of simplification to understand the ecological function of plants on key ecosystem processes. We asked whether groups of plant species based on morpho-chemical traits associated with plant persistence and stress/disturbance resistance reflect dominant plant growth forms in arid ecosystems. We selected twelve sites across an aridity gradient in northern Patagonia. At each site, we identified modal size plants of each dominant species and assessed specific leaf area (SLA), plant height, seed mass, N and soluble phenol concentration in green and senesced leaves at each plant. Plant species were grouped according with plant growth forms (perennial grasses, evergreen shrubs and deciduous shrubs) and plant morphological and/or chemical traits using cluster analysis. We calculated mean values of each plant trait for each species group and plant growth form. Plant growth forms significantly differed among them in most of the morpho-chemical traits. Evergreen shrubs were tall plants with the highest seed mass and soluble phenols in leaves, deciduous shrubs were also tall plants with high SLA and the highest N in leaves, and perennial grasses were short plants with high SLA and low concentration of N and soluble phenols in leaves. Grouping species by the combination of morpho-chemical traits yielded 4 groups in which species from one growth form prevailed. These species groups differed in soluble phenol concentration in senesced leaves and plant height. These traits were highly correlated. We concluded that (1) plant height is a relevant synthetic variable, (2) growth forms adequately summarize ecological strategies of species in arid ecosystems, and (3) the inclusion of plant morphological and chemical traits related to defenses against environmental stresses and herbivory enhanced the potential of species grouping, particularly within shrubby growth forms. PMID- 26897640 TI - Relationship Between Exercise Workload During Cardiac Rehabilitation and Outcomes in Patients With Coronary Heart Disease. AB - The purpose of this retrospective, observational study was to describe the relation between exercise workload during cardiac rehabilitation (CR), expressed as metabolic equivalents of task (METs), and prognosis among patients with coronary heart disease. We included patients with coronary heart disease who participated in CR between January 1998 and June 2007. METs were calculated from treadmill workload. Cox regression analysis was used to describe the relationship between METs and time to a composite outcome of all-cause mortality, nonfatal myocardial infarction, or heart failure hospitalization. Among 1,726 patients (36% women; median age 59 years [interquartile range, 52 to 66]), there were 467 events (27%) during a median follow-up of 5.8 years (interquartile range, 2.6 to 8.7). In analyses adjusted for age, sex, Charlson co-morbidity index, hypertension, diabetes, and CR referral diagnosis, METs were independently related to the composite outcome at CR start (Wald chi-square 43, hazard ratio 0.59 [95% confidence interval 0.51 to 0.70]) and CR end (Wald chi-square 47, hazard ratio 0.68 [95% confidence interval 0.61 to 0.76]). Patients exercising below 3.5 METs on exit from CR represent a high-risk group with 1- and 3-year event rates >=7% and >=18%, respectively. In conclusion, METs during CR is available at no additional cost and can be used to identify patients at increased risk for an event who may benefit from closer follow-up, extended length of stay in CR, and/or participation in other strategies aimed at maximizing adherence to secondary preventive behaviors and improving exercise capacity. PMID- 26897638 TI - Usefulness of Relative Hypochromia in Risk Stratification for Nonanemic Patients With Chronic Heart Failure. AB - The purpose of this study is to investigate the impact of a reduction of hemoglobin (Hb) content in the erythrocytes as estimated by mean corpuscular hemoglobin concentration (MCHC) on long-term clinical outcomes in nonanemic patients with heart failure (HF). We prospectively enrolled 1,579 subjects with HF who underwent coronary angiography enrolled in the GeneBank study with 5-year follow-up of all-cause mortality. Levels of Hb and MCHC were assessed at enrollment and after 6 months of follow-up. Anemia was defined as Hb levels <13 g/dl in men and <12 g/dl in women. In our nonanemic cohort (n = 785, 49.7%), mean Hb and median MCHC were 13.8 +/- 1.1 g/dl and 34.3 g/dL (interquartile range 33.6 to 35), respectively. Nonanemic patients with heart failure with lower MCHC had higher mortality risk (quartiles 1 vs 4, hazard ratio = 2.1, 95% confidence interval 1.4 to 3.3, p = 0.001). In a subset of nonanemic patients with persistent normal Hb on follow-up (n = 206), the mean time between baseline and follow-up MCHC levels was 169.3 +/- 41.6 days. In comparison with patients with levels of MCHC more than the first quartile (>=33.6 g/dl) on baseline and follow up, patients with persistently low MCHC (<33.6 g/dl) had a significantly increased mortality risk (log rank <0.001). All models remained significant even after adjusting for traditional cardiac risk factors, left ventricular ejection fraction, baseline Hb levels, and mean corpuscular volume. In conclusion, relative hypochromia is an independent predictor of increased mortality risk in patients with HF, even in the setting of normal Hb levels. PMID- 26897639 TI - Clinical Profile, Acute Care, and Middle-Term Outcomes of Cocaine-Associated ST Segment Elevation Myocardial Infarction in an Inner-City Community. AB - Although cocaine is a well-recognized risk factor for coronary disease, detailed information is lacking regarding related behavioral and clinical features of cocaine-associated ST-segment elevation myocardial infarction (STEMI), particularly in socioeconomically disadvantaged urban settings. Nor are systematic or extended follow-up data available on outcomes for cocaine associated STEMI in the contemporary era of percutaneous coronary intervention. We leveraged a prospective STEMI registry from a large health system serving an inner-city community to characterize the clinical features, acute management, and middle-term outcomes of cocaine-related versus cocaine-unrelated STEMI. Of the 1,003 patients included, 60% were black or Hispanic. Compared with cocaine unrelated STEMI, cocaine-related STEMI (n = 58) was associated with younger age, male gender, lower socioeconomic score, current smoking, high alcohol consumption, and human immunodeficiency virus seropositivity but less commonly with diabetes or hypertension. Cocaine users less often received drug-eluting stents or beta blockers at discharge. During median follow-up of 2.7 years, rates of death, death or any rehospitalization, and death or cardiovascular rehospitalization did not differ significantly between cocaine users and nonusers but were especially high for death or any hospitalization in the 2 groups (31.4 vs 32.4 per 100 person-years, p = 0.887). Adjusted hazard ratios for outcomes were likewise not significantly different. In conclusion, in this low-income community, cocaine use occurred in a substantial fraction of STEMI cases, who were younger than their nonuser counterparts but had more prevalent high-risk habits and exhibited similarly high rates of adverse outcomes. These data suggest that programs targeting cocaine abuse and related behaviors could contribute importantly to disease prevention in disadvantaged communities. PMID- 26897641 TI - Clear cell papillary renal cell carcinoma, renal angiomyoadenomatous tumor, and renal cell carcinoma with leiomyomatous stroma relationship of 3 types of renal tumors: a review. AB - Renal angiomyoadenomatous tumor has been described in 2000, followed by description of clear cell papillary renal cell carcinoma in 2006. Discussions about possible relationship of both tumors were published since their description. The main differential diagnostic feature was considered presence/absence of fibroleiomyomatous stroma-relationship of renal angiomyoadenomatous tumor in stroma-rich tumors. However, it was shown that stroma is reactive and nonneoplastic by its nature and that all other histologic, immunohistochemical, and molecular-genetic features of both entities are identical. In upcoming World Health Organization classification of renal tumors (2016), both lesions are considered as a single entity (clear cell papillary renal cell carcinoma [CCPRCC]). Most published cases followed the benign/indolent clinical course. In addition, most tumors has normal status of VHL gene (methylation, LOH 3p, mutations); however, CCPRCC was referred in patients with VHL syndrome. Another issue covered by this review is possible relationship of CCPRCC and "renal cell carcinoma with leiomyomatous stroma" (RCCLS). Renal cell carcinoma with leiomyomatous stroma shows clear cell cytology and abundant leiomyomatous stroma. Some of RCCLS are positive for cytokeratin 7; some are negative. Similar situation exists for relation of RCCLS and VHL gene abnormalities. It is so far unclear whether any relation between CCPRCC and RCCLS exists. From all published studies, it seems that these tumors are less likely related to each other. PMID- 26897642 TI - Paravertebral block versus thoracic epidural for patients undergoing thoracotomy. AB - BACKGROUND: Operations on structures in the chest (usually the lungs) involve cutting between the ribs (thoracotomy). Severe post-thoracotomy pain can result from pleural (lung lining) and muscular damage, costovertebral joint (ribcage) disruption and intercostal nerve (nerves that run along the ribs) damage during surgery. Poor pain relief after surgery can impede recovery and increase the risks of developing complications such as lung collapse, chest infections and blood clots due to ineffective breathing and clearing of secretions. Effective management of acute pain following thoracotomy may prevent these complications and reduce the likelihood of developing chronic pain. A multi-modal approach to analgesia is widely employed by thoracic anaesthetists using a combination of regional anaesthetic blockade and systemic analgesia, with both non-opioid and opioid medications and local anaesthesia blockade.There is some evidence that blocking the nerves as they emerge from the spinal column (paravertebral block, PVB) may be associated with a lower risk of major complications in thoracic surgery but the majority of thoracic anaesthetists still prefer to use a thoracic epidural blockade (TEB) as analgesia for their patients undergoing thoracotomy. In order to bring about a change in practice, anaesthetists need a review that evaluates the risk of all major complications associated with thoracic epidural and paravertebral block in thoracotomy. OBJECTIVES: To compare the two regional techniques of TEB and PVB in adults undergoing elective thoracotomy with respect to:1. analgesic efficacy;2. the incidence of major complications (including mortality);3. the incidence of minor complications;4. length of hospital stay;5. cost effectiveness. SEARCH METHODS: We searched for studies in the Cochrane Central Register of Controlled Trials (CENTRAL 2013, Issue 9); MEDLINE via Ovid (1966 to 16 October 2013); EMBASE via Ovid (1980 to 16 October 2013); CINAHL via EBSCO host (1982 to 16 October 2013); and reference lists of retrieved studies. We handsearched the Journal of Cardiothoracic Surgery and Journal of Cardiothoracic and Vascular Anesthesia (16 October 2013). We reran the search on 31st January 2015. We found one additional study which is awaiting classification and will be addressed when we update the review. SELECTION CRITERIA: We included all randomized controlled trials (RCTs) comparing PVB with TEB in thoracotomy, including upper gastrointestinal surgery. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Two review authors (JY and SG) independently assessed the studies for inclusion and then extracted data as eligible for inclusion in qualitative and quantitative synthesis (meta analysis). MAIN RESULTS: We included 14 studies with a total of 698 participants undergoing thoracotomy. There are two studies awaiting classification. The studies demonstrated high heterogeneity in insertion and use of both regional techniques, reflecting real-world differences in the anaesthesia techniques. Overall, the included studies have a moderate to high potential for bias, lacking details of randomization, group allocation concealment or arrangements to blind participants or outcome assessors. There was low to very low-quality evidence that showed no significant difference in 30-day mortality (2 studies, 125 participants. risk ratio (RR) 1.28, 95% confidence interval (CI) 0.39 to 4.23, P value = 0.68) and major complications (cardiovascular: 2 studies, 114 participants. Hypotension RR 0.30, 95% CI 0.01 to 6.62, P value = 0.45; arrhythmias RR 0.36, 95% CI 0.04 to 3.29, P value = 0.36, myocardial infarction RR 3.19, 95% CI 0.13, 76.42, P value = 0.47); respiratory: 5 studies, 280 participants. RR 0.62, 95% CI 0.26 to 1.52, P value = 0.30). There was moderate quality evidence that showed comparable analgesic efficacy across all time points both at rest and after coughing or physiotherapy (14 studies, 698 participants). There was moderate-quality evidence that showed PVB had a better minor complication profile than TEB including hypotension (8 studies, 445 participants. RR 0.16, 95% CI 0.07 to 0.38, P value < 0.0001), nausea and vomiting (6 studies, 345 participants. RR 0.48, 95% CI 0.30 to 0.75, P value = 0.001), pruritis (5 studies, 249 participants. RR 0.29, 95% CI 0.14 to 0.59, P value = 0.0005) and urinary retention (5 studies, 258 participants. RR 0.22, 95% CI 0.11 to 0.46, P value < 0.0001). There was insufficient data in chronic pain (six or 12 months). There was no difference found in and length of hospital stay (3 studies, 124 participants). We found no studies that reported costs. AUTHORS' CONCLUSIONS: Paravertebral blockade reduced the risks of developing minor complications compared to thoracic epidural blockade. Paravertebral blockade was as effective as thoracic epidural blockade in controlling acute pain. There was a lack of evidence in other outcomes. There was no difference in 30-day mortality, major complications, or length of hospital stay. There was insufficient data on chronic pain and costs. Results from this review should be interpreted with caution due to the heterogeneity of the included studies and the lack of reliable evidence. Future studies in this area need well-conducted, adequately-powered RCTs that focus not only on acute pain but also on major complications, chronic pain, length of stay and costs. PMID- 26897644 TI - Renewed Allegiance March 2016. PMID- 26897643 TI - Clinical Monitoring of Protein-Energy Wasting in Chronic Kidney Disease: Moving From Body Size to Body Composition. PMID- 26897645 TI - Low-intensity vibrations accelerate proliferation and alter macrophage phenotype in vitro. AB - Macrophages are essential for the efficient healing of various tissues. Although many biochemical signaling pathways have been well characterized in macrophages, their sensitivity to mechanical signals is largely unexplored. Here, we applied low-intensity vibrations (LIV) to macrophages to determine whether macrophages could directly transduce LIV signals into changes in the expression of genes and proteins involved in tissue repair. Two different LIV signal frequencies (30Hz or 100Hz) were combined with two acceleration magnitudes (0.15g or 1g) to generate four distinct LIV signals that were applied to cultured murine macrophages. All four LIV signals significantly increased macrophage number after 3 days of stimulation with the combination of the smallest acceleration and the highest frequency (0.15g at 100Hz) generating the largest response. Compared to non-LIV controls, gene expression of the pro-healing growth factors VEGF and TGF-beta increased with all four LIV signals (Day 1). LIV also decreased protein levels of the pro-inflammatory cytokines IL-6, IFN-gamma, and TNF-alpha (Days 1 and 3). These data demonstrate the sensitivity of macrophages to high-frequency oscillations applied at low intensities and may suggest that the benefit of LIV for tissue repair may be based on reducing inflammation and promoting a pro healing macrophage phenotype. PMID- 26897646 TI - In vivo simultaneous evaluations of sarcomere imaging and muscle fiber tension. AB - Muscle fiber tension and sarcomere length play critical roles in regulating muscle functions and adaptations under pathological conditions. However, methods are lacking to quantify these two variables simultaneously in vivo. A novel force microscope was developed with the unique capabilities of estimating muscle fiber tension and acquiring sarcomere images simultaneously in vivo. The force microscope consisting of a custom microscopic imaging system and a force sensor was used to quantify in vivo sarcomere length, muscle fiber tension and stress of the tibialis cranialis muscle at plantar-flexed and dorsi-flexed positions from 11 rat hind limbs. Results showed that sarcomere images and fiber tension could be measured together in vivo with significantly higher muscle fiber tension and stress and longer sarcomere length at the plantar-flexed position when compared to their counterparts at the dorsi-flexed position. The fiber tension estimated using the force microscope had close agreement with the direct measurements of the fiber tension. The present force microscope with simultaneous characterizations of fiber tension and sarcomere imaging provides us a useful in vivo tool to investigate the roles of muscle tension in regulating sarcomere and muscle fiber functions under physiological and pathological conditions. PMID- 26897647 TI - Active-passive biodynamics of the human trunk when seated on a wobble chair. AB - Unstable sitting on a wobble chair with different balance difficulty levels can be used as an effective tool in exercises as well as evaluation and therapeutic stages of rehabilitation. No data on muscle activity levels and spinal loads are however available to assess its safety compared to other regular daily activities. The goal of this study was to estimate muscle forces and spinal loads in a seated unstable wobble chair task. In vivo 3D kinematics of the trunk and seat collected in an earlier study were used here to drive computational trunk musculoskeletal models of 6 normal and 6 low-back pain subject groups sitting on a wobble chair for a duration of 10s. Results revealed no significant differences between kinematics, muscle forces, spinal loads and force plate reaction forces when comparing these two groups. The estimated muscle forces and spinal loads were moderate though larger than those in a stationary sitting posture. Local spinal forces at the L5-S1 disc varied with time and reached their peaks (1473 N and 1720 N in compression, 691 N and 687 N in posterior-anterior shear and 153 N and 208 N in right-left shear, respectively for healthy and CLBP groups) being much greater relative to those in the stationary sitting posture (means of 12 subjects: 768 N, 284 N and 0 N, respectively). The wobble chair with characteristics considered in this study is found hence safe enough as a therapeutic exercise for both healthy and low-back pain subjects. PMID- 26897648 TI - Relation between wall shear stress and carotid artery wall thickening MRI versus CFD. AB - Wall shear stress (WSS), a parameter associated with endothelial function, is calculated by computational fluid dynamics (CFD) or phase-contrast (PC) MRI measurements. Although CFD is common in WSS (WSSCFD) calculations, PC-MRI-based WSS (WSSMRI) is more favorable in population studies; since it is straightforward and less time consuming. However, it is not clear if WSSMRI and WSSCFD show similar associations with vascular pathology. Our aim was to test the associations between wall thickness (WT) of the carotid arteries and WSSMRI and WSSCFD. The subjects (n=14) with an asymptomatic carotid plaque who underwent MRI scans two times within 4 years of time were selected from the Rotterdam Study. We compared WSSCFD and WSSMRI at baseline and follow-up. Baseline WSSMRI and WSSCFD values were divided into 3 categories representing low, medium and high WSS tertiles. WT of each tertile was compared by a one-way ANOVA test. The WSSMRI and WSSCFD were 0.50+/-0.13Pa and 0.73+/-0.25Pa at baseline. Although WSSMRI was underestimated, a significant regression was found between WSSMRI and WSSCFD (r(2)=0.71). No significant difference was found between baseline and follow-up WSS by CFD and MRI-based calculations. The WT at baseline was 1.36+/-0.16mm and did not change over time. The WT was 1.55+/-0.21mm in low, 1.33+/-0.20mm in medium and 1.21+/-0.21mm in the high WSSMRI tertiles. Similarly, the WT was 1.49+/-0.21mm in low, 1.33+/-0.20mm in medium and 1.26+/-0.21mm in high WSSCFD tertiles. We found that WSSMRI and WSSCFD were inversely related with WT. WSSMRI and WSSCFD patterns were similar although MRI-based calculations underestimated WSS. PMID- 26897649 TI - Emulating constant acceleration locomotion mechanics on a treadmill. AB - Locomotion on an accelerating treadmill belt is not dynamically similar to overground acceleration. The purpose of this study was to test if providing an external force to compensate for inertial forces during locomotion on an accelerating treadmill belt could induce locomotor dynamics similar to real accelerations. Nine males (mean+/-sd age=26+/-4 years, mass=81+/-9kg, height=1.8+/-0.05m) began walking and transitioned to running on an accelerating instrumented treadmill belt at three accelerations (0.27ms(-2), 0.42ms(-2), 0.76ms(-2)). Half the trials were typical treadmill locomotion (TT) and half were emulated acceleration (EA), where elastic tubing harnessed to the participant provided a horizontal force equal to mass multiplied by acceleration. Net mechanical work (WCOM) and ground reaction force impulses (IGRF) were calculated for individual steps and a linear regression was performed with these experimental measures as independent variables and theoretically derived values of work and impulse as predictor variables. For EA, linear fits were significant for WCOM (y=1.19x+10.5, P<0.001, R(2)=0.41) and IGRF (y=0.95x+8.1, P<0.001, R(2)=0.3). For TT, linear fits were not significant and explained virtually no variance for WCOM (y=0.06x+1.6, P=0.29, R(2)<0.01) and IGRF (y=0.10x+0.4, P=0.06, R(2)=0.01). This suggested that the EA condition was a better representation of real acceleration dynamics than TT. Running steps from EA where work and impulse closely matched theoretical values showed similar adaptations to increasing acceleration as have been previously observed overground (forward reorientation of GRF vector without an increase in magnitude or change in spatio-temporal metrics). PMID- 26897650 TI - Falls resulting from a laboratory-induced slip occur at a higher rate among individuals who are obese. AB - Falls due to slipping are a serious concern, with slipping estimated to cause 40 50% of all fall-related injuries. Epidemiological data indicates that older and obese adults experience more falls than young, non-obese individuals. An increasingly heavier and older U.S. population and workforce may be exacerbating the problem of slip-induced falls. The purpose of this study was to investigate the effects of obesity and age on slip severity and rate of falling resulting from laboratory-induced slips. Four groups of participants (young obese, young non-obese, older obese, older non-obese) were slipped while walking at a self selected, slightly hurried pace. Slip severity (slip distance, slip duration, mean slip speed and peak slip speed) and slip outcome (fall or recovery) were compared between groups. Obese individuals experienced 22% faster slips than non obese individuals in terms of mean slip speed (p=0.022). Obesity did not affect slip distance, slip duration or peak slip speed. Obese individuals also exhibited a higher rate of falls; 32% of obese individuals fell compared to 10% of non obese (p=0.005). Obese individuals were more than eight times more likely to experience a fall than non-obese individuals when adjusting for age, gender and gait speed. No age effects were found for slip severity or slip outcome. These results, along with epidemiological data reporting higher fall rates among the obese, indicate that obesity may be a significant risk factor for experiencing slip-induced falls. Slip severity thresholds were also reported that may have value in developing controls for fall prevention. PMID- 26897651 TI - Physical properties and hydration behavior of a fast-setting bioceramic endodontic material. AB - BACKGROUND: To investigate the physical properties and the hydration behaviour of the fast-setting bioceramic iRoot FS Fast Set Root Repair Material (iRoot FS) and three other endodontic cements. METHODS: iRoot FS, Endosequence Root Repair Material Putty (ERRM Putty), gray and white mineral trioxide aggregate (G-MTA & W MTA), and intermediate restorative material (IRM) were evaluated. The setting time was measured using ANSI/ADA standards. Microhardness was evaluated using the Vickers indentation test. Compressive strength and porosity were investigated at 7 and 28 days. Differential scanning calorimetry (DSC) was employed for the hydration test. RESULTS: iRoot FS had the shortest setting time of the four bioceramic cements (p < .001). The microhardness values of iRoot FS, ERRM Putty and MTA increased at different rates over the 28 days period. At day one, ERRM Putty had the lowest microhardness of the bioceramic cements (p < .001), but reached the same level as MTA at 4, 7 and 28 days. The microhardness of iRoot FS was lower than that of W-MTA at 7 and 28 days (p < .05). The porosity of the materials did not change after 7 days (p < .05). The compressive strength values at 28 days were significantly greater for all bioceramic groups compared to those at 7 days (p < .01). ERRM Putty had the highest compressive strength and the lowest porosity of the evaluated bioceramic cements (p < .05), followed by iRoot FS, W-MTA, and G-MTA, respectively. DSC showed that iRoot FS hydrated fastest, inducing an intense exothermic reaction. The ERRM Putty did not demonstrate a clear exothermic peak during the isothermal calorimetry test. CONCLUSIONS: iRoot FS had a faster setting time and hydrating process than the other bioceramic cements tested. The mechanical properties of iRoot FS, G-MTA and W-MTA were relatively similar. PMID- 26897652 TI - In situ mobility of uranium in the presence of nitrate following sulfate-reducing conditions. AB - Reoxidation and mobilization of previously reduced and immobilized uranium by dissolved-phase oxidants poses a significant challenge for remediating uranium contaminated groundwater. Preferential oxidation of reduced sulfur-bearing species, as opposed to reduced uranium-bearing species, has been demonstrated to limit the mobility of uranium at the laboratory scale yet field-scale investigations are lacking. In this study, the mobility of uranium in the presence of nitrate oxidant was investigated in a shallow groundwater system after establishing conditions conducive to uranium reduction and the formation of reduced sulfur-bearing species. A series of three injections of groundwater (200 L) containing U(VI) (5 MUM) and amended with ethanol (40 mM) and sulfate (20 mM) were conducted in ten test wells in order to stimulate microbial-mediated reduction of uranium and the formation of reduced sulfur-bearing species. Simultaneous push-pull tests were then conducted in triplicate well clusters to investigate the mobility of U(VI) under three conditions: 1) high nitrate (120 mM), 2) high nitrate (120 mM) with ethanol (30 mM), and 3) low nitrate (2 mM) with ethanol (30 mM). Dilution-adjusted breakthrough curves of ethanol, nitrate, nitrite, sulfate, and U(VI) suggested that nitrate reduction was predominantly coupled to the oxidation of reduced-sulfur bearing species, as opposed to the reoxidation of U(IV), under all three conditions for the duration of the 36-day tests. The amount of sulfate, but not U(VI), recovered during the push-pull tests was substantially more than injected, relative to bromide tracer, under all three conditions and further suggested that reduced sulfur-bearing species were preferentially oxidized under nitrate-reducing conditions. However, some reoxidation of U(IV) was observed under nitrate-reducing conditions and in the absence of detectable nitrate and/or nitrite. This suggested that reduced sulfur bearing species may not be fully effective at limiting the mobility of uranium in the presence of dissolved and/or solid-phase oxidants. The results of this field study confirmed those of previous laboratory studies which suggested that reoxidation of uranium under nitrate-reducing conditions can be substantially limited by preferential oxidation of reduced sulfur-bearing species. PMID- 26897653 TI - Soil memory as a potential mechanism for encouraging sustainable plant health and productivity. AB - The unspecified components of plant-microbe and plant-microbiome associations in the rhizosphere are complex, but recent research is simplifying our understanding of these relationships. We propose that the strong association between hosts, symbionts, and pathogens could be simplified by the concept of soil memory, which explains how a plant could promote their fecundity and protect their offspring through tightly associated relationships with the soil. Although there are many questions surrounding the mechanisms of this phenomenon, recent research has exposed evidence of its existence. Along with evidence from observations and mechanisms related to soil memory, we report means to utilize our understanding as sustainable protection for agricultural crops and propose future research questions. PMID- 26897654 TI - Pathogenesis by subviral agents: viroids and hepatitis delta virus. AB - The viroids of plants are the simplest known infectious genetic elements. They have RNA genomes of up to 400 nucleotides in length and no protein encoding capacity. Hepatitis delta virus (HDV), an infectious agent found only in humans co-infected with hepatitis B virus (HBV), is just slightly more complex, with an RNA genome of about 1700 nucleotides, and the ability to express just one small protein. Viroid and HDV RNAs share several features that include circular structure, compact folding, and replication via a rolling-circle mechanism. Both agents were detected because of their obvious pathogenic effects. Their simplicity demands a greater need than conventional RNA or DNA viruses to redirect host components for facilitating their infectious cycle, a need that directly and indirectly incites pathogenic effects. The mechanisms by which these pathogenic effects are produced are the topic of this review. In this context, RNA silencing mediates certain aspects of viroid pathogenesis. PMID- 26897655 TI - Experiences Accessing Abortion Care in Alabama among Women Traveling for Services. AB - BACKGROUND: In Alabama, more than one-half of reproductive-aged women live in counties without an abortion provider. State regulations require in-person counseling (or confirmed receipt of materials sent by certified mail) followed by a 48-hour waiting period. We explored the impact of this service and policy environment on experiences accessing abortion care for women traveling long distances to clinics. METHODS: We conducted in-depth interviews with 25 women who traveled more than 30 miles to an Alabama clinic providing abortion care between July and September 2014. Women were interviewed by telephone at least 1 day after their consultation, procedure, or follow-up visit. We used content analysis methods to code and analyze interview transcripts. FINDINGS: Almost all women found a clinic by searching online or talking to others in their social networks who had abortions. These strategies did not always direct women to the closest clinic, and some described searches that yielded inaccurate information. The majority of women did not believe an in-person consultation visit was necessary and found it to be burdensome because of the extra travel required and long waits at the clinic. Two-thirds of the women were unable to schedule their abortion 48 hours later owing to work schedules or because appointments were offered only once a week, and four women were delayed until their second trimester even though they sought services earlier in pregnancy. CONCLUSIONS: It is often difficult for women in communities without an abortion provider to find and access timely abortion care. Efforts are needed to make abortion more accessible and prevent further restrictions on services. PMID- 26897658 TI - Clinical studies stemming from the Taiwan National Health Insurance Database. PMID- 26897656 TI - CHARM, a gender equity and family planning intervention for men and couples in rural India: protocol for the cluster randomized controlled trial evaluation. AB - BACKGROUND: Globally, 41% of all pregnancies are unintended, increasing risk for unsafe abortion, miscarriage and maternal and child morbidities and mortality. One in four pregnancies in India (3.3 million pregnancies, annually) are unintended; 2/3 of these occur in the context of no modern contraceptive use. In addition, no contraceptive use until desired number and sex composition of children is achieved remains a norm in India. Research shows that globally and in India, the youngest and most newly married wives are least likely to use contraception and most likely to report husband's exclusive family planning decision-making control, suggesting that male engagement and family planning support is important for this group. Thus, the Counseling Husbands to Achieve Reproductive Health and Marital Equity (CHARM) intervention was developed in recognition of the need for more male engagement family planning models that include gender equity counseling and focus on spacing contraception use in rural India. METHODS/DESIGN: For this study, a multi-session intervention delivered to men but inclusive of their wives was developed and evaluated as a two-armed cluster randomized controlled design study conducted across 50 mapped clusters in rural Maharashtra, India. Eligible rural young husbands and their wives (N = 1081) participated in a three session gender-equity focused family planning program delivered to the men (Sessions 1 and 2) and their wives (Session 3) by village health providers in rural India. Survey assessments were conducted at baseline and 9&18 month follow-ups with eligible men and their wives, and pregnancy tests were obtained from wives at baseline and 18-month follow-up. Additional in-depth understanding of how intervention impact occurred was assessed via in-depth interviews at 18 month follow-up with VHPs and a subsample of couples (n = 50, 2 couples per intervention cluster). Process evaluation was conducted to collect feedback from husbands, wives, and VHPs on program quality and to ascertain whether program elements were implemented according to curriculum protocols. Fidelity to intervention protocol was assessed via review of clinical records. DISCUSSION: All study procedures were completed in February 2015. Findings from this work offer important contributions to the growing field of male engagement in family planning, globally. TRIAL REGISTRATION: ClinicalTrial.gov, NCT01593943. PMID- 26897659 TI - Thoughts On Life. PMID- 26897657 TI - Reduction of Seclusion and Restraint in an Inpatient Psychiatric Setting: A Pilot Study. AB - The authors describe a quality and safety initiative designed to decrease seclusion/restraint (S/R) and present the results of a pilot study that evaluated the effectiveness of this program. The study sample consisted of consecutive admissions to a 120-bed psychiatric service after the intervention was implemented (October 2010-September 2012, n = 8029). Analyses compared S/R incidence and duration in the study sample to baseline (consecutive admissions during the year prior to introduction of the intervention, October 2008-September 2009, n = 3884). The study intervention, which used evidence-based therapeutic practices for reducing violence/aggression, included routine use of the Broset Violence Checklist, mandated staff education in crisis intervention and trauma informed care, increased frequency of physician reassessment of need for S/R, formal administrative review of S/R events and environmental enhancements (e.g., comfort rooms to support sensory modulation). Statistically significant associations were found between the intervention and a decrease in both the number of seclusions (p < 0.01) and the duration of seclusion per admission (p < 0.001). These preliminary results support the conclusion that this intervention was effective in reducing use of seclusion. Further study is needed to determine if these prevention strategies are generalizable, the degree to which each component of the intervention contributes to improve outcome, and if continuation of the intervention will further reduce restraint use. PMID- 26897661 TI - Does Uncontrolled Platelet Activation Promote Coronary Artery Disease? PMID- 26897662 TI - Echocardiographic Findings and Clinical Correlation With Cardiac Myxoma. PMID- 26897660 TI - Control of Mosquito-Borne Infectious Diseases: Sex and Gene Drive. AB - Sterile male releases have successfully reduced local populations of the dengue vector, Aedes aegypti, but challenges remain in scale and in separating sexes before release. The recent discovery of the first mosquito male determining factor (M factor) will facilitate our understanding of the genetic programs that initiate sexual development in mosquitoes. Manipulation of the M factor and possible intermediary factors may result in female-to-male conversion or female killing, enabling efficient sex separation and effective reduction of target mosquito populations. Given recent breakthroughs in the development of CRISPR Cas9 reagents as a source of gene drive, more advanced technologies at driving maleness, the ultimate disease refractory phenotype, become possible and may represent efficient and self-limiting methods to control mosquito populations. PMID- 26897663 TI - Sickle Cardiomyopathy: The Missing Forest in the Trees. PMID- 26897664 TI - Chemotherapy-Induced Valvular Heart Disease. PMID- 26897665 TI - The Relation of Ejection Fraction and Global Longitudinal Strain in Amyloidosis: Implications for Differential Diagnosis. PMID- 26897666 TI - Valvular Dysfunction in Lymphoma Survivors Treated With Autologous Stem Cell Transplantation: A National Cross-Sectional Study. AB - OBJECTIVES: This study assessed the prevalence and associated risk factors for valvular dysfunction (VD) observed in adult lymphoma survivors (LS) after autologous hematopoietic stem cell transplantation (auto-HCT), and to determine whether anthracycline-containing chemotherapy (ACCT) alone in these patients is associated with VD. BACKGROUND: The prevalence of and risk factors for VD in LS after auto-HCT is unknown. Anthracyclines may induce heart failure, but any association with VD is not well-defined. METHODS: This national cross-sectional study included all adult LS receiving auto-HCT from 1987 to 2008 in Norway. VD was defined by echocardiography as either more than mild regurgitation or any stenosis. Observations in LS were compared with a healthy age- and gender-matched (1:1) control group. RESULTS: In total, 274 LS (69% of all eligible) participated. Mean age was 56 +/- 12 years, mean follow-up time after lymphoma diagnosis was 13 +/- 6 years, and 62% of participants were males. Mean cumulative anthracycline dosage was 316 +/- 111 mg/m(2), and 35% had received radiation therapy involving the heart (cardiac-RT). VD was observed in 22.3% of the LS. Severe VD was rare (n = 9; 3.3% of all LS) and mainly aortic stenosis (n = 7). We observed VD in 16.7% of LS treated with ACCT alone (n = 177), corresponding with a 3-fold increased VD risk (odds ratio: 2.9; 95% confidence interval: 1.5 to 5.8; p = 0.002) compared with controls. Furthermore, the presence of aortic valve degeneration was increased in the LS after ACCT alone compared with controls (13.0% vs. 2.9%; p < 0.001). Female sex, age >50 years at lymphoma diagnosis, >=3 lines of chemotherapy before auto-HCT, and cardiac-RT >30 Gy were identified as independent risk factors for VD in the LS. CONCLUSIONS: In LS, ACCT alone was significantly associated with VD and related to valvular degeneration. Overall, predominantly moderate VD was prevalent in LS, and longer observation time is needed to clarify the clinical significance of this finding. PMID- 26897667 TI - Workstation-Based Calculation of CTA-Based FFR for Intermediate Stenosis. AB - OBJECTIVES: This study sought to evaluate the proportion of patients with intermediate coronary stenosis diagnosed on computed tomography angiography (CTA), which may be saved from any further testing due to use of CTA-based fractional flow reserve (FFR). BACKGROUND: Coronary CTA often results in diagnosis of intermediate stenosis, triggering further physiological testing. CTA based FFR (CTA-FFR) is a promising diagnostic tool, which may obviate the need for further testing. However, the specific thresholds for CTA-FFR values predicting ischemic versus nonischemic FFR with acceptable confidence are unknown, obscuring clinical utility of the diagnostic strategy using CTA-FFR. METHODS: We analyzed 96 lesions (mean CTA stenosis: 69.7 +/- 11.7%) in 90 patients (63.4 +/- 8.2 years, 32% were men) who underwent CTA for suspected CAD and were diagnosed with at least 1 intermediate coronary stenosis (50% to 90%) scheduled for further physiological testing. All patients underwent routine invasive FFR and CTA-FFR evaluation. The objective was to determine the proportion of patients falling between the lower and upper CTA-FFR thresholds that predict ischemic and nonischemic stenosis, respectively (on the basis of an invasive FFR cutpoint of <=0.80), with >=90% accuracy. RESULTS: The invasive FFR <=0.8 was observed in 41 of 96 lesions (42.7%). According to Bland-Altman analysis, the CTA-FFR underestimated FFR by 0.01 and the 95% limits of agreement were +/-0.19. Receiver-operating characteristic area under the curve was significantly higher for CTA-FFR than that for CTA (per lesion 0.835 vs. 0.660, respectively; p = 0.007). The CTA-FFR thresholds for which the positive and negative predictive values were each >=90% (corresponding to an FFR of <=0.80) were >0.87 or <0.74, respectively, encompassing 49 lesions (51%) and 45 of 90 patients. CONCLUSIONS: In around one-half of the patients diagnosed with intermediate stenosis, coronary CTA-based FFR may confidently discriminate between ischemic versus nonischemic stenoses. Our findings require validation in an independent cohort. PMID- 26897668 TI - Role of PET Imaging in Management of Implantable Electronic Device Infection. PMID- 26897669 TI - CT Angiography for the Prediction of Hemodynamic Significance in Intermediate and Severe Lesions: Head-to-Head Comparison With Quantitative Coronary Angiography Using Fractional Flow Reserve as the Reference Standard. AB - OBJECTIVES: The goal of this study was to compare the diagnostic performance of coronary computed tomography angiography (CTA) versus quantitative coronary angiography (QCA) for the detection of lesion-specific ischemia using fractional flow reserve (FFR) as the gold standard. BACKGROUND: Coronary CTA has emerged as a noninvasive method for accurate detection and exclusion of high-grade coronary stenoses. FFR is the gold standard for determining lesion-specific ischemia and has been shown to improve clinical outcomes when guiding revascularization. METHODS: A total of 252 patients from 5 countries were prospectively enrolled (mean age 63 years; 71% male). Patients underwent coronary CTA and invasive coronary angiography (ICA) with FFR in 407 lesions. Coronary CTA, QCA, and FFR were interpreted by independent core laboratories. Stenosis severity according to coronary CTA and QCA were graded as 0% to 29%, 30% to 49%, 50% to 69%, and 70% to 100%; stenosis >=50% was considered anatomically obstructive. Lesion-specific ischemia was defined according to FFR <=0.8, whereas QCA and coronary CTA stenosis >=50% were considered obstructive. Diagnostic accuracy and areas under the receiver-operating characteristics curve (AUC) for lesion-specific ischemia was assessed. RESULTS: According to FFR, ischemia was present in 151 (37%) of 407 lesions. Diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 69%, 79%, 63%, 55%, and 83% for coronary CTA; and 71%, 74%, 70%, 59%, and 82% for QCA. AUC for identification of ischemia-causing lesions was similar: 0.75 for coronary CTA and 0.77 for QCA (p = 0.6). No differences between CTA and QCA existed for discrimination of ischemia within the left anterior descending artery (AUC 0.71 vs. 0.73; p = 0.6), left circumflex artery (AUC 0.78 vs. 0.85; p = 0.4), and right coronary artery (AUC 0.80 vs. 0.83; p = 0.6). CONCLUSIONS: CTA and ICA exhibited similar diagnostic performance for the detection and exclusion of lesion-specific ischemia. Using a true reference standard to determine appropriate revascularization targets, 3 dimensional coronary CTA performed as well as 2-dimensional ICA. PMID- 26897670 TI - Vasospastic Angina and Hemodynamic Injury. PMID- 26897671 TI - The Authors Reply. PMID- 26897672 TI - The Authors Reply. PMID- 26897673 TI - Heart Rate Is an Important Consideration for Cardiac Imaging of Diastolic Function. PMID- 26897674 TI - Prospective Evaluation of Cardiac CT in Reoperative Cardiac Surgery. PMID- 26897675 TI - Relationship Between Platelet Reactivity and Culprit Lesion Morphology: An Assessment From the ADAPT-DES Intravascular Ultrasound Substudy. AB - OBJECTIVES: This study evaluated the relationship between platelet reactivity and plaque morphology using grayscale and radiofrequency intravascular ultrasound (IVUS) virtual histology (VH). BACKGROUND: Recent studies have reported that high on-treatment platelet reactivity (HPR) is associated with higher plaque volume and the presence of multivessel disease; however, the association between HPR and plaque morphology has not been evaluated. METHODS: The ADAPT-DES (Dual AntiPlatelet Therapy With Drug Eluting Stents) intravascular ultrasound substudy was a prospective, multicenter, observational study of 8,582 patients undergoing percutaneous coronary intervention with drug-eluting stents in whom platelet reactivity on clopidogrel was assessed routinely. The current analysis included 909 culprit lesions from 773 patients with pre-intervention grayscale IVUS and IVUS-VH. HPR was defined as platelet reactivity >208 P2Y12 reaction unit in point of-care P2Y12 testing by the VerifyNow assay, measured during steady-state platelet inhibition in patients receiving an antiplatelet agent. RESULTS: HPR was associated with 3-vessel coronary artery disease (31.0% vs. 24.4%; p = 0.04). The incidence of fibroatheroma was higher in patients with HPR than those without HPR (77.1% vs. 68.9%; p = 0.01). The HPR group had larger percent plaque and media volume (plaque and media/external elastic membrane volume: 58.1% [95% confidence interval (CI): 57.1% to 59.0%] vs. 56.6% [95% CI: 55.8% to 57.5%]; p = 0.03) and plaque burden at the minimum lumen site (76.7% [95% CI: 75.7% to 77.8%] vs. 75.0% [95% CI: 74.0% to 76.0%]; p = 0.02). Despite a similar prevalence of attenuated plaque, patients with HPR had longer culprit lesion attenuated plaque length (8.0 [95% CI: 7.0 to 9.1] mm vs. 6.5 [95% CI: 5.9 to 7.1] mm; p = 0.01). On multivariate analysis, the presence of angiographic calcium (odds ratio [OR]: 1.85: 95% CI: 1.33 to 2.56; p = 0.0002) and HPR (OR: 1.45; 95% CI: 1.05 to 2.01; p = 0.02) were independent predictors for a culprit lesion fibroatheroma. CONCLUSIONS: HPR was associated with increased culprit lesion atherosclerotic burden and adverse plaque morphology among patients undergoing percutaneous coronary intervention. Platelet reactivity might be associated with not only blood clot formation, but also severity of atherosclerosis. (Assessment of Dual AntiPlatelet Therapy With Drug Eluting Stents [ADAPT-DES]; NCT00638794). PMID- 26897676 TI - Mitral Annular Dimensions and Geometry in Patients With Functional Mitral Regurgitation and Mitral Valve Prolapse: Implications for Transcatheter Mitral Valve Implantation. AB - OBJECTIVES: The aims of this study were to determine D-shaped mitral annulus (MA) dimensions in control subjects without significant cardiac disease and in patients with moderate to severe mitral regurgitation (MR) being considered for transcatheter mitral therapy and to determine predictors of annular size, using cardiac computed tomography. BACKGROUND: The recently introduced D-shaped method of MA segmentation represents a biomechanically appropriate approach for annular sizing prior to transcatheter mitral valve implantation. METHODS: Patients who had retrospectively gated cardiac computed tomography performed at our institution (2012 to 2014) and were free of significant cardiac disease were included as controls (n = 88; 56 +/- 11 years of age; 47% female) and were compared with patients with moderate or severe MR due to functional mitral regurgitation (FMR) (n = 27) or mitral valve prolapse (MVP) (n = 32). MA dimensions (projected area, perimeter, intercommissural, and septal-to-lateral distance), maximal left atrial (LA) volumes, and phasic left ventricular volumes were measured. RESULTS: MA dimensions were larger in patients with FMR or MVP compared with controls (area index 4.7 +/- 0.6 cm(2)/m(2), 6.0 +/- 1.3 cm(2)/m(2), and 7.3 +/- 1.7 cm(2)/m(2); perimeter index 59 +/- 5 mm/m(2), 67 +/- 9 mm/m(2), and 75 +/- 10 mm/m(2); intercommissural distance index 20.2 +/- 1.9 mm/m(2), 21.2 +/- 3.1 mm/m(2), and 24.7 +/- 3.2 mm/m(2); septal-to-lateral distance index 14.8 +/- 1.6, 18.1 +/- 3.3, and 19.5 +/- 3.4 mm/m(2) in controls and patients with FMR and MVP, respectively; p < 0.05 between controls and MR subgroups). Absolute MA area was 18% larger in patients with MVP than patients with FMR (13.0 +/- 2.9 cm(2) vs. 11.0 +/- 2.3 cm(2); p = 0.006). Although LA and left ventricular volumes were both independently associated with MA area index in controls and patients with MVP, only LA volume was associated with annular size in patients with FMR. CONCLUSIONS: Moderate to severe MR was associated with increased MA dimensions, especially among patients with MVP compared with control subjects without cardiac disease. Moreover, unlike in controls and patients with MVP, annular enlargement in FMR was more closely associated with LA dilation. PMID- 26897677 TI - The Authors Reply. PMID- 26897678 TI - Right Ventricle Involvement in Tako-Tsubo Cardiomyopathy. PMID- 26897679 TI - The Authors Reply. PMID- 26897680 TI - From Newton to the Coronaries: Computational Fluid Dynamics Has Entered the Clinical Scene. PMID- 26897681 TI - Is the Heart Really Stressed Out of Energy? PMID- 26897682 TI - The Authors Reply. PMID- 26897683 TI - Contribution of PET Imaging to the Diagnosis of Septic Embolism in Patients With Pacing Lead Endocarditis. AB - OBJECTIVES: The aim of this study was to investigate the role of 18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) scanning in identifying septic embolism in patients with lead endocarditis. BACKGROUND: Lead endocarditis may be associated with septic embolism, in which case the administration mode, type, and duration of antibiotic therapy must be adapted. However, diagnosis can be challenging: magnetic resonance imaging (MRI) cannot be performed in the vast majority of patients with cardiac implantable electronic devices (CIEDs). FDG PET/CT scanning has been proposed as a diagnostic tool for suspected CIED infection. METHODS: Thirty-five consecutive patients with lead endocarditis were prospectively studied. FDG PET/CT scanning was performed and analyzed blindly by experienced nuclear medicine physicians to assess for the presence of septic embolism 2 days before lead extraction. RESULTS: FDG PET/CT scanning identified septic emboli in 10 patients (29%): 7 with spondylodiscitis, 2 with septic pulmonary emboli, and 1 with an infected vascular prosthesis. Among the 7 patients with occult spondylodiscitis, 4 were asymptomatic, and 3 had back pain with negative CT imaging, MRI being contraindicated due to non MRI compatible CIEDs. Antimicrobial therapy was adapted (double antibiotic therapy with good bone penetration) and prolonged. Among other important ancillary findings, 3 patients presented focal FDG uptake in the colon (1 adenocarcinoma, and 2 resected polyps) and 2 in the esophagus (both cases confirmed as neoplasia). CONCLUSIONS: This study emphasizes the potential utility of FDG PET/CT scanning as a diagnostic tool for septic emboli in patients with pacing lead endocarditis. This promising diagnostic tool may be integrated in the diagnostic algorithm of patients with lead endocarditis because diagnosis of septic embolisms has a direct and significant impact on the therapeutic care pathway. PMID- 26897685 TI - Sizing the Mitral Annulus: Is CT the Future? PMID- 26897686 TI - LA Size in Former Elite Athletes. PMID- 26897684 TI - The Need for Standardized Methods for Measuring the Aorta: Multimodality Core Lab Experience From the GenTAC Registry. AB - OBJECTIVES: This study sought to evaluate variability in aortic measurements with multiple imaging modalities in clinical centers by comparing with a standardized measuring protocol implemented in a core laboratory. BACKGROUND: In patients with aortic disease, imaging of thoracic aorta plays a major role in risk stratifying individuals for life-threatening complications and in determining timing of surgical intervention. However, standardization of the procedures for performance of aortic measurements is lacking. METHODS: To characterize the diversity of methods used in clinical practice, we compared aortic measurements performed by echocardiography, computed tomography (CT), and magnetic resonance imaging (MRI) at the 6 GenTAC (National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions) clinical centers to those performed at the imaging core laboratory in 965 studies. Each center acquired and analyzed their images according to local protocols. The same images were subsequently analyzed blindly by the core laboratory, on the basis of a standardized protocol for all imaging modalities. Paired measurements from clinical centers and core laboratory were compared by mean of differences and intraclass correlation coefficient (ICC). RESULTS: For all segments of the ascending aorta, echocardiography showed a higher ICC (0.84 to 0.93) than CT (0.84) and MRI (0.82 to 0.90), with smaller mean of differences. MRI showed higher ICC for the arch and descending aorta (0.91 and 0.93). In a mixed adjusted model, the different imaging modalities and clinical centers were identified as sources of variability between clinical and core laboratory measurements, whereas age groups or diagnosis at enrollment were not. CONCLUSIONS: By comparing core laboratory with measurements from clinical centers, our study identified important sources of variability in aortic measurements. Furthermore, our findings with regard to CT and MRI suggest a need for imaging societies to work toward the development of unifying acquisition protocols and common measuring methods. PMID- 26897688 TI - Right Heart Score for Predicting Outcome in PAH: Is It All Inclusive? PMID- 26897689 TI - Association Between Nonstenosing Carotid Artery Plaque on MR Angiography and Acute Ischemic Stroke. PMID- 26897690 TI - What Will it Take to Retire Invasive Coronary Angiography? PMID- 26897687 TI - Cardiomyopathy With Restrictive Physiology in Sickle Cell Disease. AB - OBJECTIVES: The aim of this study was to identify a unifying cardiac pathophysiology that explains the cardiac pathological features in sickle cell disease (SCD). BACKGROUND: Cardiopulmonary complications, the leading cause of adult death in SCD, are associated with heart chamber dilation, diastolic dysfunction, elevated tricuspid regurgitant jet velocity (TRV), and pulmonary hypertension. However, no unifying cardiac pathophysiology has been identified to explain these findings. METHODS: In a 2-part study, we first examined patients with SCD who underwent screening echocardiography during steady state at our institution. We then conducted a meta-analysis of cardiac studies in SCD. RESULTS: In the 134 patients with SCD studied (median age 11 years), significant enlargement of the left atrial volume was present (z-score 3.1, p = 0.002), shortening fraction was normal (37.6 +/- 4.7%), and lateral and septal ratios of mitral velocity to early diastolic velocity of the mitral annulus (E/e') were severely abnormal in 8% and 14% of patients, respectively, indicating impaired diastolic function. Both TRV and lateral E/e' correlated with enlarged left atrial volume in SCD (p = 0.003 and p = 0.006, respectively). Meta-analysis of 68 studies confirmed significant left atrial diameter enlargement in patients with SCD compared with controls, evidence of diastolic dysfunction and enlarged left ventricular end-diastolic dimension with normal shortening fraction. The majority of patients with catheter-confirmed pulmonary hypertension had mild pulmonary venous hypertension consistent with restrictive cardiac physiology. CONCLUSIONS: Patients with SCD have a unique form of cardiomyopathy with restrictive physiology that is superimposed on hyperdynamic physiology and is characterized by diastolic dysfunction, left atrial dilation, and normal systolic function. This combination results in mild, secondary, pulmonary venous hypertension and elevated TRV. Sudden death is common in other forms of restrictive cardiomyopathy. Our finding of this unique restrictive cardiomyopathy may explain the increased mortality rates and sudden death seen in patients with SCD with mildly elevated TRV. PMID- 26897691 TI - The Author Replies. PMID- 26897693 TI - How Exactly Do You Measure That Aorta?: Lessons From Multimodality Imaging. PMID- 26897692 TI - Cardiac CT With Delayed Enhancement in the Characterization of Ventricular Tachycardia Structural Substrate: Relationship Between CT-Segmented Scar and Electro-Anatomic Mapping. AB - OBJECTIVES: This study sought to compare myocardial scars depicted by computed tomography (CT) with electrical features from electro-anatomic mapping (EAM), assessing the potential role of CT integration in ventricular tachycardia (VT) and radiofrequency catheter ablation (RFCA) procedures. BACKGROUND: Imaging-based characterization of VT myocardial substrate is required to plan EAM and, potentially, to guide RFCA. METHODS: Forty-two consecutive patients, 35 of whom had implantable cardioverter-defibrillator, all referred for VT RFCA, underwent pre-procedural CT including an angiographic and a 10-min delayed-enhancement scan. Segmental comparison between scars segmented from CT and low voltages (bipolar voltages <1.5 mV; unipolar voltages <8 mV), late potentials, and RF ablation points on EAM, was carried out. In a subset of 16 consecutive patients, a further point-by-point analysis was performed: a CT-derived 3-dimensional structure including heart anatomy and myocardial scars was integrated with EAM for quantitative comparison. RESULTS: CT scans identified scars in 39 patients and defined left ventricular wall involvement and mural distribution. Overall segmental concordance between CT and EAM was good (kappa = 0.536) despite the presence of implantable cardioverter-defibrillator, scar etiologies, and mural distribution. CT identified segments characterized by low voltages with good sensitivity (76%), good specificity (86%), and very high negative predictive value (95%). Late potentials and RF ablation points fell on scarred segments identified from CT in 79% and 81% of cases, respectively. Point-by-point quantitative comparison revealed good correlation between the average area of scar detected at CT and at bipolar mapping (CT = 4,901 mm(2), bipolar voltages EAM = 4,070 mm(2); R = 0.78; p < 0.0001). In this study, 70% and 84% of low amplitude bipolar points were mapped at a maximum distance of 5 mm and 10 mm from CT-segmented scar, respectively. CONCLUSIONS: CT with delayed-enhancement provides a 3-dimensional characterization of VT scar substrate together with a detailed anatomic model of the heart. This information may offer assistance to plan EAM and RFCA procedures and is potentially suitable for EAM-imaging integration. PMID- 26897694 TI - A highly precautionary doffing sequence for health care workers after caring for wet Ebola patients to further reduce occupational acquisition of Ebola. PMID- 26897695 TI - The influence of using antibiotic-coated peripherally inserted central catheters on decreasing the risk of central line-associated bloodstream infections. AB - The use of peripherally inserted central catheters (PICCs) has increased over the past few years due to their less serious insertion complications. The purpose of the present study was to determine whether patients receiving PICCs impregnated with minocycline and rifampin had a lower rate of CLABSI compared with a concurrent control group of patients receiving uncoated PICCs. PMID- 26897696 TI - A pseudo-outbreak of foodborne illness in a hospital cafeteria caused by consumption of sorbitol. PMID- 26897697 TI - Hand hygiene compliance in Penang, Malaysia: Human audits versus product usage. AB - Hand hygiene auditing is mandatory for all Malaysian public hospitals; nonetheless, the burden of auditing is impacting the support and sustainability of the program. We report an alternative method to routinely measure hand hygiene compliance with the aim to test whether alcohol-based handrub purchase data could be used as a proxy for usage because human auditing has decreased validity and reliability inherent in the methodology. PMID- 26897698 TI - Assessing patient and caregiver understanding of and satisfaction with the use of contact isolation. AB - BACKGROUND: Contact isolation is a method used for limiting the spread of antimicrobial-resistant organisms when caring for patients. This policy has been linked to several adverse outcomes and less patient satisfaction. We assessed patient and caregiver understanding and satisfaction with the use of contact isolation. METHODS: A prospective survey of >500 patients in contact isolation at our institution was performed during 2014. Participants responded to a series of statements relating to contact isolation, using a 5-point Likert scale. Responses were assessed for overall positivity or negativity and further compared according to floor type or designation. RESULTS: Of the patients, 48.7% responded to the survey; 70 caregivers also responded. Patient and caregiver responses were similar and were positive overall. Most respondents felt safer because of the use of contact isolation and because it prevented infections. A smaller majority of respondents also thought the policy was adequately explained to them and adhered to by staff. CONCLUSIONS: In the largest collection of respondents surveyed to date about contact isolation and its impact on them, the policy was viewed positively, both by patients and caregivers. There is still room for improvement in the area of patient education regarding the use of contact isolation. PMID- 26897699 TI - Evaluation of the effectiveness of manual and automated dialyzers reprocessing after multiple reuses. AB - A cross-sectional study was conducted to evaluate the effectiveness of manual and automated dialyzer reprocessing. Dialyzers were filled with fluid thioglycollate medium from blood and dialysate chambers after being reprocessed and chemically sterilized with 0.2% peracetic acid. They were incubated for 14 days at 35 degrees C +/- 2 degrees C, and microbiologic analysis was performed. Microorganisms were identified in 3 of the 11 samples (27.3%) from the blood chambers: Sphingomonas paucimobilis (2/3) and Penicillium spp (1/3) and in 11 of the 11 samples (100%) from the dialysate chambers: S paucimobilis (7/11), Stenotrophomonas maltophilia (4/11), Pseudomonas aeruginosa (3/11), Candida spp (1/11), and Acinetobacter baumannii (1/11). Of the 4 manually reprocessed dialyzers, gram-positive bacillus were identified in 1 sample (25%) from the blood chamber, and Bacillus spp and Burkholderia spp were identified in 1 sample (25%) from the dialysate chamber. The dialyzers reprocessing can pose risks safety because of exposure patient to microorganisms. PMID- 26897700 TI - Attitudes and perceptions of health care workers in Northeastern Germany about multidrug-resistant organisms. AB - There were 256 health care workers in 39 facilities who were interviewed about their perceptions of the quality of care of patients with and without multidrug resistant organisms based on a standardized questionnaire. There are remarkable differences in the responses between facility types (acute care hospitals, long term care hospitals, rehabilitation hospitals, and home care services). Hygiene management must be specifically tailored to the requirements of each facility. PMID- 26897701 TI - Visual-spatial ability is more important than motivation for novices in surgical simulator training: a preliminary study. AB - OBJECTIVE: To investigate whether surgical simulation performance and previous video gaming experience would correlate with higher motivation to further train a specific simulator task and whether visual-spatial ability would rank higher in importance to surgical performance than the above. It was also examined whether or not motivation would correlate with a preference to choose a surgical specialty in the future and if simulator training would increase the interest in choosing that same work field. METHODS: Motivation and general interest in surgery was measured pre- and post-training in 30 medical students at Karolinska Institutet who were tested in a laparoscopic surgical simulator in parallel with measurement of visual-spatial ability and self-estimated video gaming experience. Correlations between simulator performance metrics, visual-spatial ability and motivation were statistically analyzed using regression analysis. RESULTS: A good result in the first simulator trial correlated with higher self-determination index (r =-0.46, p=0.05) in male students. Visual-spatial ability was the most important underlying factor followed by intrinsic motivation score and finally video gaming experience (p=0.02, p=0.05, p=0.11) regarding simulator performance in male students. Simulator training increased interest in surgery when studying all subjects (p=0.01), male subjects (p=0.02) as well as subjects with low video gaming experience (p=0.02). CONCLUSIONS: This preliminary study highlights individual differences regarding the effect of simulator training on motivation that can be taken into account when designing simulator training curricula, although the sample size is quite small and findings should be interpreted carefully. PMID- 26897702 TI - Anomalous Origin of the Right Vertebral Artery: Incidence and Significance. AB - OBJECTIVE: Detailed knowledge about anatomic variations of the aortic arch and its multiple branches is extremely important to endovascular and diagnostic radiologists. It is often hypothesized that anomalous origin and distribution of large aortic vessels may alter the cerebral hemodynamics and potentially lead to a vascular pathology. METHODS: In this article, we describe a case of anomalous origin of the right vertebral artery, which was detected during an intervention. We further reviewed the available literature of anomalous origin of the right vertebral artery. The probable embryologic development and clinical significance are discussed. RESULTS: The incidence of anomalous origin of a vertebral artery seems to be underestimated in recent literature. A careful review of the literature shows more than 100 such cases. The right vertebral artery can arise from the aortic arch or one of its branches. Dual origin of the vertebral artery is not uncommon. The embryologic developmental hypotheses are contradictory and complex. CONCLUSIONS: Anomalous origin of the right vertebral artery may not be the sole reason behind a disease process. However, it can certainly lead to a misdiagnosis during diagnostic vascular studies. Detailed information is essential for any surgery or endovascular intervention in this location. PMID- 26897703 TI - Natural selenium particles from Staphylococcus carnosus: Hazards or particles with particular promise? AB - Various bacteria, including diverse Staphylococci, reduce selenite to yield red selenium particles with diameters in the high nanometer to low micrometer range. Formation and accumulation of such particles in bacteria often results in cell death, triggered by a loss of thiols and formation of disruptive deposits inside the cell. Hence certain pathogenic bacteria are rather sensitive to the presence of selenite, whilst other organisms, such as small nematodes, do not employ this kind of nanotechnology, yet become affected by micromolar concentrations of such naturally generated materials. Selenium particles extracted from cultures of Staphylococcus carnosus and apparently stabilized by their natural protein coating, for instance, show considerable activity against the nematode Steinernema feltiae, Escherichia coli and Saccaromyces cerevisiae. Such natural nano- and micro-particles are also more active than mechanically generated selenium particles and may be applied as antimicrobial materials in Medicine and Agriculture. PMID- 26897704 TI - Baseline biopsychosocial determinants of telomere length and 6-year attrition rate. AB - BACKGROUND: Short leukocyte telomere length (TL) and accelerated telomere attrition have been associated with various deleterious health outcomes, although their determinants have not been explored collectively in a large-scale study. MATERIAL AND METHODS: Leukocyte TL was measured (baseline N=2936; 6-year follow up N=1860) in participants (18-65 years) from the NESDA study. Baseline determinants of TL included sociodemographics, lifestyle, chronic diseases, psychosocial stressors, and metabolic and physiological stress markers. Multivariate linear regression models were used to examine the associations between these determinants and (1) baseline TL, and (2) 6-year TL change. Multinomial logistic regression analyses were used to examine the predictors of telomere attrition and lengthening, as compared to stable TL. RESULTS: Short baseline TL was associated with older age, male sex, non-European ethnicity, cigarette smoking, recent life events, and higher triglycerides, glucose and pre ejection period (R(2)=11.3%). The 6-year telomere attrition was inversely associated with baseline TL (R(2)=51.6%); also older age, long sleep, not having a partner, high childhood trauma index, and gastrointestinal disease were associated with 6-year TL attrition (additional R(2)=3.7%). Telomere attrition seemed to have slightly more predictors than lengthening. CONCLUSIONS: Sociodemographic, lifestyle, psychosocial stress and metabolic and physiological stress factors are cross-sectionally linked with TL. Telomere attrition over six years was strongly associated with baseline TL, suggesting an internal homeostatic influence. Modulation of the identified determinants may become target of future studies to promote telomere maintenance and healthy aging. PMID- 26897708 TI - Are we consistent in using 14 different units for brain natriuretic peptide instead of ng/L? PMID- 26897706 TI - Prevalence and intensity of bacteraemia following orthodontic procedures. AB - BACKGROUND: There is a possibility that bacteria may enter the blood stream during some non-surgical manipulation procedures, which include orthodontic treatment procedures (alginate impression taking, separator placement, band cementation, and archwire change). OBJECTIVES: The aim of this study was to determine the prevalence and intensity of bacteraemia associated with orthodontic procedures in patients seen at the Lagos University Teaching Hospital, Nigeria. METHODOLOGY: A total of 100 subjects who presented at the Orthodontic Clinic of the Lagos University Teaching Hospital and who met the inclusion criteria were recruited for the study. Four orthodontic procedures were investigated: alginate impression taking, separator placement, band cementation and archwire placement. Subjects were randomly placed in one of the four procedure groups. Peripheral blood was collected for microbiologic analysis before the orthodontic procedures and within 2 min of completion of the procedures. The BACTEC automated blood culture system and the lysis filtration method of blood culturing were used for microbiological analysis of the blood samples. The Wilcoxon signed rank test, the McNemar chi(2) test, the Mann-Whitney U-test, and Spearman and point bi-serial correlations were used for statistical evaluation at the P<0.05 level. RESULTS: A significant increase in the prevalence and intensity of bacteraemia was observed following separator placement. The predominant bacteria isolated from the blood cultures were Streptococcus viridans and Staphylococcus species. CONCLUSION: Separator placement induced the highest levels of bacteraemia. Use of a 0.2% chlorhexidine mouth rinse is recommended prior to separator placement in orthodontic patients. PMID- 26897707 TI - Fiberoptic intubation or video tube for trauma patient intubation--which method to choose? Randomized crossover manikin trial. PMID- 26897709 TI - Identification of steroleosin in oil bodies of pine megagametophytes. AB - Three classes of integral proteins termed oleosin, caleosin and steroleosin have been identified in seed oil bodies of diverse angiosperm species. Recently, two oleosin isoforms and one caleosin were identified in megagametophyte oil bodies of pine (Pinus massoniana), a representative gymnosperm species. In this study, a putative steroleosin of approximately 41 kDa was observed in isolated oil bodies of pine megagametophytes, and its corresponding cDNA fragment was obtained by PCR cloning and further confirmed by mass spectrometric analysis. Phylogenetic tree analysis showed that pine steroleosin was evolutionarily more closely-related to steroleosin-B than steroleosin-A found in angiosperm seed oil bodies. As expected, artificial oil bodies constituted with recombinant steroleosin over expressed in Escherichia coli were less stable and larger than native pine oil bodies. Filipin staining of artificial oil bodies sheltered by recombinant steroleosin with or without its sterol binding domain showed that the sterol binding domain was responsible for the sterol binding capability of steroleosin. Sterol-coupling dehydrogenase activity was demonstrated in artificial oil bodies constituted with recombinant steroleosin as well as in purified pine oil bodies. PMID- 26897711 TI - Letter From the Editors. PMID- 26897710 TI - Involvement of Bacteria Other Than Clostridium difficile in Antibiotic-Associated Diarrhoea. AB - Antibiotic-associated diarrhoea (AAD) is a common and unintended consequence of antibiotic use. Clostridium difficile is the most common infectious aetiology of AAD; however, only approximately 25% of all AAD cases are associated with C. difficile infection, with the aetiology in the majority of cases remaining undetermined. Numerous other bacterial infectious agents have been implicated in AAD, including Clostridium perfringens, Staphylococcus aureus, and Klebsiella oxytoca. AAD is a complex disease that is influenced by the host, the infectious agent involved, and numerous clinical factors, including antibiotic treatment regimes. This review re-examines AAD and presents current perspectives on this disease, with a particular focus on the current understanding of bacterial causes other than C. difficile and the virulence factors involved in pathogenesis. VIDEO ABSTRACT. PMID- 26897712 TI - Letter From the Guest Editor. PMID- 26897713 TI - Treatment of Metastatic Bone Disease and the Emerging Role of Radium-223. AB - Bone metastases are common in advanced malignancy and, despite the developments in both anticancer and bone-targeted therapies in recent years, new therapeutic strategies are still needed. Traditionally, radioisotopes have been rarely used in part owing to concerns about bone marrow toxicity that limits retreatment and may prevent safe administration of subsequent chemotherapy. Radium-223 dichloride (Ra-223) is a calcium mimetic that binds preferentially to newly formed bone in areas of bone metastases, is the first alpha-emitting radionuclide to be developed for clinical use, and is approved for treatment of castration-resistant prostate cancer and symptomatic bone metastases. In this setting, it improves overall survival and delays symptomatic skeletal complications. The high linear energy transfer of the emitted alpha particles causes predominantly nonrepairable double-stranded deoxyribonucleic acid breaks in tumor cells, and the large size of the alpha particle, compared with other forms of radiation, results in a short path length and highly localized tissue destruction. As a result, Ra-223 has a highly favorable safety profile with a low level of myelosuppression. The role of Ra-223 in malignancy is discussed and the prospects for future development outlined. PMID- 26897714 TI - Yttrium-90 Radioembolization for Hepatocellular Carcinoma. AB - (90)Y radioembolization refers to the selective, transcatheter, and intra arterial injection of micrometer-sized particles loaded with the radioisotope yttrium-90 for the treatment of primary and metastatic hepatic malignancies. In the treatment of intermediate- and advanced-stage hepatocellular carcinoma, (90)Y radioembolization provides favorable outcomes with minimal side effects, offering an alternative treatment option to other transarterial therapies, such as bland embolization and chemoembolization. This review provides an overview of the use of (90)Y radioembolization in the treatment of hepatocellular carcinoma, including patient selection criteria, dosimetry, and clinical outcomes. PMID- 26897716 TI - Radioimmunotherapy and Autologous Stem-Cell Transplantation in the Treatment of B Cell Non-Hodgkin Lymphoma. AB - High-dose chemotherapy and autologous stem-cell transplantation (ASCT) is the standard therapy for patients with chemosensitive-relapsed or chemosensitive refractory aggressive lymphoma. The use of rituximab, an anti-CD20 monoclonal antibody, has dramatically changed the outcome of patients with aggressive lymphoma, increasing both response and survival rates. However, despite this progress a significant proportion of patients are still refractory or relapse after frontline rituximab-containing therapy. Moreover, it is increasingly more difficult to rescue these patients with current salvage chemotherapy and ASCT approaches. Novel approaches are needed for these high-risk patients, especially in the rituximab era. Radioimmunotherapy (RIT) is a form of targeted therapy using the parent monoclonal antibody to deliver radiation emitted by a conjugated radioisotope, to the vicinity of antigen-positive tissues. Two radioimmunoconjugates--yttrium-90 ibritumomab tiuxetan (Zevalin) and iodine-131 tositumomab (Bexxar) have been in clinical use. There are multiple studies demonstrating the safety and efficacy of both agents in both indolent and aggressive lymphoma. Radiolabeled antibodies are ideal candidates to combine with high-dose chemotherapy and ASCT. RIT targets radiation to disease sites while limiting exposure of uninvolved critical organs, thus it can safely replace total body irradiation during conditioning for ASCT. The major toxicity and limiting factor in RIT is myelotoxicity that is easily reversed by stem-cell rescue. RIT can be combined at standard doses with high-dose chemotherapy or can be given in escalated doses either alone or with high-dose chemotherapy before ASCT. Several phase II studies have shown the safety and potential efficacy of both agents using these approaches. A small randomized study comparing standard-dose Zevalin with combination of carmustine, etoposide, cytarabine, and melphalan (BEAM) high dose chemotherapy and BEAM alone suggested a survival advantage of Zevalin-BEAM. However, a large randomized study comparing Bexxar-BEAM and rituximab-BEAM did not show any advantage. More studies are needed to establish the role and the dose of RIT given for ASCT. PMID- 26897717 TI - Y-90 Radiomicrosphere Therapy for Colorectal Cancer Liver Metastases. AB - At present, the systemic treatment of unresectable colorectal cancer liver metastases involves oxaliplatin and irinotecan-based chemotherapy regimens combined with targeted therapies such as bevacizumab (Avastin) and cetuximab (Erbitux). Radiation therapy, traditionally, is not considered a viable treatment modality owing to its unacceptably high hepatic toxicity, and still steering traditional wisdom or dogma that chemoradiation cannot be an oncological strategy for a stage IV disease. Selective internal radiation treatment with yttrium-90 (Y 90) radiomicrospheres has emerged as an effective liver-directed therapy with a favorable therapeutic ratio. Since its early clinical trials, it has demonstrated improved response rates when used in conjunction with systemic or regional chemotherapy. This article reviews the clinical role for Y-90 radiomicrosphere therapy in the contemporary management of colorectal cancer liver metastases. All the structured clinical trials, to date, are summarized, including those that studied the value of combined Y-90 radiomicrosphere therapy and current chemotherapy protocols. PMID- 26897715 TI - Novel Approaches to Thyroid Cancer Treatment and Response Assessment. AB - The incidence of thyroid cancer has been increasing. After total thyroidectomy of well-differentiated thyroid tumors with intermediate- or high-risk features on pathology, radioiodine remains one of the mainstays of therapy for both thyroid remnant ablation as well as for treatment of metastatic disease. SPECT/CT, a relatively new modality, has been shown to play a pivotal role predominantly in the post-therapy setting by changing the risk stratification of patients with thyroid cancer. In the case of radioiodine treatment failure, FDG-PET/CT may provide prognostic information based on extent and intensity of metabolically active metastatic sites as well as serve as an important imaging test for response assessment in patients treated with chemotherapy, targeted therapies, or radiotherapy, thereby affecting patient management in multiple ways. The role of newer redifferentiation drugs has been evaluated with the use of I-124 PET/CT. PMID- 26897718 TI - Radioimmunotherapy for Treatment of Acute Leukemia. AB - Acute leukemias are characterized by accumulation of immature cells (blasts) and reduced production of healthy hematopoietic elements. According to the lineage origin, two major leukemias can be distinguished: acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL). Although the survival rate for pediatric ALL is close to 90%, half of the young adults with AML or ALL and approximately 90% of older patients with AML or ALL still die of their disease, raising the need for innovative therapeutic approaches. As almost all leukemic blasts express specific surface antigens, targeted immunotherapy appears to be particularly promising. However, published results of immunotherapy alone are generally modest. Radioimmunotherapy (RIT) brings additional therapeutic mechanisms using radiolabeled monoclonal antibodies (mAbs) directed to tumor antigens, thus adding radiobiological cytotoxicity to immunologic cytotoxicity. Because of the high radiosensitivity of tumor cells and the diffuse widespread nature of the disease, making it rapidly accessible to circulating radiolabeled mAbs, acute leukemias represent relevant indications for RIT. With the development of recombinant and humanized mAbs, innovative radionuclides, and more efficient radiolabeling and pretargeting techniques, RIT has significantly improved over the last 10 years. Different approaches of alpha and beta RIT targeting CD22, CD33, CD45, or CD66 antigens have already been evaluated or are currently being developed in the treatment of acute leukemia. This review summarizes the preclinical and clinical studies demonstrating the potential of RIT in treatment of AML and ALL. PMID- 26897719 TI - Management of Differentiated Thyroid Cancer in Children: Focus on the American Thyroid Association Pediatric Guidelines. AB - First introduced in 1946, radioactive iodine (I-131) produces short-range beta radiation with a half-life of 8 days. The physical properties of I-131 combined with the high degree of uptake in the differentiated thyroid cancers (DTCs) led to the use of I-131 as a therapeutic agent for DTC in adults. There are two indications for the potential use of I-131 therapy in pediatric thyroid disorders: nonsurgical treatment of hyperthyroidism owing to Graves' disease and the treatment of children with intermediate- and high-risk DTC. However, children are not just miniature adults. Not only are children and the pediatric thyroid gland more sensitive to radiation than adults but also the biologic behavior of DTC differs between children and adults as well. As opposed to adults, children with DTC typically present with advanced disease at diagnosis; yet, they respond rapidly to therapy and have an excellent prognosis that is significantly better than that in adult counterparts with advanced disease. Unfortunately, there are also higher rates of local and distant disease recurrence in children with DTC compared with adults, mandating lifelong surveillance. Further, children have a longer life expectancy during which the adverse effects of I-131 therapy may become manifest. Recognizing the differences between adults and children with DTC, the American Thyroid Association commissioned a task force of experts who developed and recently published a guideline to address the unique issues related to the management of thyroid nodules and DTC in children. This article reviews the epidemiology, diagnosis, staging, treatment, therapy-related effects, and suggestions for surveillance in children with DTC, focusing not only on the differences between adults and children with this disease but also on the latest recommendations from the inaugural pediatric management guidelines of the American Thyroid Association. PMID- 26897720 TI - Radioimmunotherapy for Prostate Cancer--Current Status and Future Possibilities. AB - Prostate cancer (PCa) is one of the most common cancers in men and is the second leading cause of cancer-related deaths in the USA. In the United States, it is the second most frequently diagnosed cancer after skin cancer, and in Europe it is number one. According to the American Cancer Society, approximately 221,000 men in the United States would be diagnosed with PCa during 2015, and approximately 28,000 would die of the disease. According to the International Agency for Research on Cancer, approximately 345,000 men were diagnosed with PCa in Europe during 2012, and despite more emphasis placed on early detection through routine screening, 72,000 men died of the disease. Hence, the need for improved therapy modalities is of utmost importance. And targeted therapies based on radiolabeled specific antibodies or peptides are a very interesting and promising alternative to increase the therapeutic efficacy and overall chance of survival of these patients. There are currently several preclinical and some clinical studies that have been conducted, or are ongoing, to investigate the therapeutic efficacy and toxicity of radioimmunotherapy (RIT) against PCa. One thing that is lacking in a lot of these published studies is the dosimetry data, which are needed to compare results between the studies and the study locations. Given the complicated tumor microenvironment and overall complexity of RIT to PCa, old and new targets and targeting strategies like combination RIT and pretargeting RIT are being improved and assessed along with various therapeutic radionuclides candidates. Given alone or in combination with other therapies, these new and improved strategies and RIT tools further enhance the clinical response to RIT drugs in PCa, making RIT for PCa an increasingly practical clinical tool. PMID- 26897722 TI - Grief and loss for patients before and after heart transplant. AB - OBJECTIVES: The purpose of the study was to examine the loss and grief experiences of patients waiting for and living with new hearts. BACKGROUND: There is much scholarship on loss and grief. Less attention has been paid to these issues in clinical transplantation, and even less on the patient experience. METHODS: Part of a qualitative inquiry oriented to the work of Merleau-Ponty, a secondary analysis was carried out on audiovisual data from interviews with thirty participants. RESULTS: Patients experience loss and three forms of grief. Pre-transplant patients waiting for transplant experience loss and anticipatory grief related to their own death and the future death of their donor. Transplanted patients experience long-lasting complicated grief with respect to the donor and disenfranchised grief which may not be sanctioned. CONCLUSIONS: Loss as well as anticipatory, complicated and disenfranchised grief may have been inadvertently disregarded or downplayed. More research and attention is needed. PMID- 26897723 TI - Several metabolic risk factors in subjects with increased plasma adiponectin levels: Causality of positive associations. PMID- 26897721 TI - MicroRNAs in Rice Innate Immunity. AB - MicroRNAs (miRNAs) are short regulatory non-coding RNAs that guide gene silencing in most eukaryotes. They regulate gene expression by triggering sequence-specific cleavage or translational repression of target transcripts. Plant miRNAs are known to play important roles in a wide range of developmental processes. Increasing evidence also supports that the modulation of miRNA levels plays an important role in reprogramming plant responses to abiotic stress (drought, cold, salinity and nutrient deficiency) and biotic stress (antibacterial resistance). Most of these studies were carried out in the model plant Arabidopsis thaliana. During the last years, the adoption of high-throughput sequencing technologies has significantly contributed to uncover multiple miRNAs while allowing miRNA profiling in plants. However, although a plethora of rice miRNAs have been shown to be regulated by pathogen infection, the biological function remains largely unknown for most of them. In this review, we summarize our current understanding on the contribution of miRNAs to rice immunity and discuss their potential applications in rice biotechnology. A better understanding of the miRNA species controlling rice immunity may lead to practical biotechnological applications leading to the development of appropriate strategies for rice protection. PMID- 26897724 TI - Reducing pain by moving? A commentary on Ferre et al. 2013. PMID- 26897725 TI - Singly-qualified medical senior house officer in oral and maxillofacial surgery: perspectives from a unit. AB - Despite constituting a minority of senior house officers (SHO) in oral and maxillofacial surgery (OMFS), the number of singly-qualified medical trainees is growing. We describe the experience of a singly qualified medical trainee in OMFS and the unique benefits and opportunities for potential trainees and the department. Overall, the advantages of synergistic training outweigh any deficiencies in knowledge, and in our experience, having both medical and dental trainees in our unit has maximised training opportunities and provided a more holistic approach to patient care. Increased exposure to conditions in the head and neck also benefits trainees who wish to pursue careers in other specialties such as ear, nose, and throat (ENT), neurosurgery, ophthalmology, and plastic surgery. PMID- 26897733 TI - What We Can Learn from Experts and Expertise with Fenestrated and Branched Stent Grafts: The "Croissant-Doughnut" Concept for Post-dissection Aneurysm Repair. PMID- 26897734 TI - Commentary on 'Rupture of Abdominal Aortic Aneurysms in Patients under Screening Age and Elective Repair Threshold'. PMID- 26897735 TI - Profile of refractive errors in European Caucasian children with Autistic Spectrum Disorder; increased prevalence and magnitude of astigmatism. AB - PURPOSE: Autistic Spectrum Disorder (ASD) is a common neurodevelopmental disorder characterised by impairment of communication, social interaction and repetitive behaviours. Only a small number of studies have investigated fundamental clinical measures of vision including refractive error. The aim of this study was to describe the refractive profile of a population of children with ASD compared to typically developing (TD) children. METHODS: Refractive error was assessed using the Shin-Nippon NVision-K 5001 open-field autorefractor following the instillation of cyclopentolate hydrochloride 1% eye drops. RESULTS: A total of 128 participants with ASD (mean age 10.9 +/- 3.3 years) and 206 typically developing participants (11.5 +/- 3.1 years) were recruited. There was no significant difference in median refractive error, either by spherical equivalent or most ametropic meridian between the ASD and TD groups (Spherical equivalent, Mann-Whitney U307 = 1.15, p = 0.25; Most Ametropic Meridian, U305 = 0.52, p = 0.60). Median refractive astigmatism was -0.50DC (range 0.00 to -3.50DC) for the ASD group and -0.50DC (Range 0.00 to -2.25DC) for the TD group. Magnitude and prevalence of refractive astigmatism (defined as astigmatism >=1.00DC) was significantly greater in the ASD group compared to the typically developing group (ASD 26%, TD 8%, magnitude U305 = 3.86, p = 0.0001; prevalence (chi12=17.71 , p < 0.0001). CONCLUSIONS: This is the first study to describe the refractive profile of a population of European Caucasian children with ASD compared to a TD population of children. Unlike other neurodevelopmental conditions, there was no increased prevalence of spherical refractive errors in ASD but astigmatic errors were significantly greater in magnitude and prevalence. This highlights the need to examine refractive errors in this population. PMID- 26897736 TI - Kinematic analysis of ankle stiffness in subjects with and without flat foot. AB - BACKGROUND: Although the magnitude of ankle motion is influenced by joint congruence and ligament elasticity, there is a lack of understanding on ankle stiffness between subjects with and without flat foot. OBJECTIVE: This study investigated a quantified ankle stiffness difference between subjects with and without flat foot. METHODS: There were forty-five age- and gender-matched subjects who participated in the study. Each subject was seated upright with the tested foot held firmly onto a footplate that was attached to a torque sensor by the joint-driving device. RESULTS: The flat foot group (mean +/- standard deviation) demonstrated increased stiffness during ankle dorsiflexion (0.37 +/- 0.16 for flat foot group, 0.28 +/- 0.10 for control group; t=-2.11, p=0.04). However, there was no significant group difference during plantar flexion (0.35 +/- 0.15 for flat foot group, 0.33 +/- 0.07 for control group; t=0.64, p=0.06). CONCLUSION: The results of this study indicated that the flat foot group demonstrated increased ankle stiffness during dorsiflexion regardless of demographic factors. This study highlights the need for kinematic analyses and joint stiffness measures during ankle dorsiflexion in subjects with flat foot. PMID- 26897737 TI - Can Clinical Guidelines Afford to Ignore Cost Effectiveness? An Ethical Perspective. PMID- 26897738 TI - Reply to the letter by Takeshi Yamada et al. concerning "Is serum HER2 ECD a predictive biomarker for response to trastuzumab in advanced gastric cancer?". PMID- 26897739 TI - No weekend effect on outcomes of severe acute pancreatitis in Japan: data from the diagnosis procedure combination database. AB - BACKGROUND: In the early phase of severe acute pancreatitis, timely multidisciplinary management is required to reduce mortality. The aim of this observational study was to evaluate the impact of weekend hospital admission on outcomes using population-based data in Japan. METHODS: Data on adult patients (>=20 years) with severe acute pancreatitis were extracted from a nationwide Japanese administrative database covering over 1000 hospitals. In-hospital mortality, length of stay, and total costs were compared between weekend and weekday admissions, with adjustment for disease severity according to the current Japanese severity scoring system for acute pancreatitis, and other potential risk factors. RESULTS: In total, 8328 patients hospitalized during the study period 2010-2013 were analyzed (2242 admitted at weekends and 6086 on weekdays). In hospital mortality rates were not significantly different: 5.9 vs. 5.4 % for weekend and weekday admissions, respectively (multivariate-adjusted odds ratio, 1.06; 95 % confidence interval, 0.83-1.35). The impact of weekend admission was not significant either for length of hospitalization (median, 18 vs. 19 days) and total costs (median, 6161 vs. 6233 US dollars) (both p > 0.19 in multivariate adjusted linear regression). The rates of, and time to, specific treatments were also similar between patients with weekend and weekday admissions. CONCLUSIONS: A weekend effect in severe acute pancreatitis admissions was not evident. Adjustments to weekend staffing and selective hospital referral of patients admitted at weekends are not indicated for severe acute pancreatitis in current clinical practice in Japan. PMID- 26897741 TI - Macrophages or retinal pigment epithelium expressing macrophage markers in age related macular degeneration? Comment on Lad et al. 2015. PMID- 26897740 TI - Fecal calprotectin: its scope and utility in the management of inflammatory bowel disease. AB - Gastrointestinal symptoms such as abdominal pain, dyspepsia, and diarrhea are relatively nonspecific and a common cause for seeking medical attention. To date, it is challenging for physicians to differentiate between functional and organic gastrointestinal conditions and it involves the use of serological and endoscopic techniques. Therefore, a simple, noninvasive, inexpensive, and effective test would be of utmost importance in clinical practice. Fecal calprotectin (FC) is considered to be a reliable biomarker that fulfills these criteria. FC can detect intestinal inflammation, and its level correlates well with macroscopic and histological inflammation as detected by colonoscopy and biopsies, respectively. FC has a decent diagnostic accuracy for differentiating organic diseases and functional disorders because of its excellent negative predictive value in ruling out inflammatory bowel disease (IBD) in symptomatic undiagnosed patients. There is accumulating evidence that FC has been effectively used to monitor the natural course of IBD, to predict relapse, and to see the response to treatment. This novel biomarker has the ability to assess mucosal healing (MH), which is a therapeutic goal in IBD management. A literature search was carried out using PubMed with the keywords FC, IBD, intestinal inflammation, and MH. In our review, we provide an overview of the utility and scope of FC as a biomarker in patients with IBD as well as undiagnosed patients with lower gastrointestinal symptoms. PMID- 26897742 TI - Key role of MEK/ERK pathway in sustaining tumorigenicity and in vitro radioresistance of embryonal rhabdomyosarcoma stem-like cell population. AB - BACKGROUND: The identification of signaling pathways that affect the cancer stem like phenotype may provide insights into therapeutic targets for combating embryonal rhabdomyosarcoma. The aim of this study was to investigate the role of the MEK/ERK pathway in controlling the cancer stem-like phenotype using a model of rhabdospheres derived from the embryonal rhabdomyosarcoma cell line (RD). METHODS: Rhabdospheres enriched in cancer stem like cells were obtained growing RD cells in non adherent condition in stem cell medium. Stem cell markers were evaluated by FACS analysis and immunoblotting. ERK1/2, myogenic markers, proteins of DNA repair and bone marrow X-linked kinase (BMX) expression were evaluated by immunoblotting analysis. Radiation was delivered using an x-6 MV photon linear accelerator. Xenografts were obtained in NOD/SCID mice by subcutaneously injection of rhabdosphere cells or cells pretreated with U0126 in stem cell medium. RESULTS: MEK/ERK inhibitor U0126 dramatically prevented rhabdosphere formation and down-regulated stem cell markers CD133, CXCR4 and Nanog expression, but enhanced ALDH, MAPK phospho-active p38 and differentiative myogenic markers. By contrast, MAPK p38 inhibition accelerated rhabdosphere formation and enhanced phospho-active ERK1/2 and Nanog expression. RD cells, chronically treated with U0126 and then xeno-transplanted in NOD/SCID mice, delayed tumor development and reduced tumor mass when compared with tumor induced by rhabdosphere cells. U0126 intraperitoneal administration to mice bearing rhabdosphere-derived tumors inhibited tumor growth . The MEK/ERK pathway role in rhabdosphere radiosensitivity was investigated in vitro. Disassembly of rhabdospheres was induced by both radiation or U0126, and further enhanced by combined treatment. In U0126-treated rhabdospheres, the expression of the stem cell markers CD133 and CXCR4 decreased and dropped even more markedly following combined treatment. The expression of BMX, a negative regulator of apoptosis, also decreased following combined treatment, which suggests an increase in radiosensitivity of rhabdosphere cells. CONCLUSIONS: Our results indicate that the MEK/ERK pathway plays a prominent role in maintaining the stem-like phenotype of RD cells, their survival and their innate radioresistance. Thus, therapeutic strategies that target cancer stem cells, which are resistant to traditional cancer therapies, may benefit from MEK/ERK inhibition combined with traditional radiotherapy, thereby providing a promising therapy for embryonal rhabdomyosarcoma. PMID- 26897743 TI - Is cardiac and hepatic iron status assessed by MRI T2* associated with left ventricular function in patients with idiopathic cardiomyopathy? AB - Excess accumulation of iron in the heart is known to aggravate cardiac function in some cases of genetic and acquired iron overload. We investigated the possible association between cardiac function and iron content in the heart and liver, estimated non-invasively by T2 star (T2*)-weighted magnetic resonance (MR) imaging among patients with cardiomyopathy. MR images were acquired on a 3.0 T MR imaging system using an 8-channel phased-array cardiac coil. Average T2* values of the heart were estimated at regions of interest that were located on short axis mid-ventricular slices positioned at the cardiac septum. In total, 82 patients were enrolled: 48 patients with dilated cardiomyopathy (DCM), 16 patients with hypertrophic cardiomyopathy (HCM), and 18 patients without apparent cardiovascular abnormalities. Cardiac T2* values were lower in the DCM group (median 18.6 ms) than in the HCM (22.0 ms) and control (21.4 ms) groups, although hepatic T2* values did not differ significantly across the groups. Among the whole population, the highest cardiac T2* tertile (>=21.2 ms) was significantly negatively associated with a low left ventricular ejection fraction (LVEF) of <50 %, and this association retained statistical significance after adjustment for sex, age, renal function, hemoglobin and hepatic T2*. Among DCM patients, both hemoglobin and cardiac T2* were selected as parameters that were, respectively, negatively and positively, associated with LVEF (P < 0.05). DCM patients with lower cardiac T2*, and thus higher iron content, were found to have lower LVEF. The possibility that cardiac iron overload may have a role in reducing the systolic cardiac function in DCM patients who do not have systemic iron overload requires further investigation in the future. PMID- 26897745 TI - Living conditions and quality of care in residential units for people with long term mental illness in Portugal--a cross-sectional study. AB - BACKGROUND: As in most European countries, mental health care has shifted from large hospitals to smaller community based settings in Portugal. Our study objectives were to determine: a) the characteristics of users of mental health residential facilities in Portugal; b) the quality of care provided comparing community and hospital units; and c) to investigate associations between quality of care, service and service users' characteristics and experiences of care. METHODS: All longer term mental health units in Portugal providing on-site staffed support for at least 12 h per day were assessed with the Quality Indicator for Rehabilitative Care (QuIRC), a standardised tool completed by the unit manager. The QuIRC rates seven domains of care (Living Environment, Therapeutic Environment, Treatments and Interventions, Self/Management and Autonomy, Recovery Based Practice, Social Inclusion, and Human Rights). A random sample of service users were interviewed using standardised measures of autonomy, experiences of care and quality of life. RESULTS: Most (60 %) of the 42 units were in Lisbon and surrounding districts with 50 % based in the community and 50 % in hospital settings. They had a mean of 11.5 beds. Service users (n = 278) were mainly men (66.2 %), with a diagnosis of schizophrenia (72.7 %), and a mean age of 49.4 years. Community units scored higher than hospital units on the Living Environment, Treatments and Interventions, and Self-Management and Autonomy domains of the QuIRC. Increased service user age was negatively associated with all but one domain. All QuIRC domains were positively associated with service users' autonomy and experiences of care. CONCLUSIONS: Investing in better quality, community based mental health facilities is associated with better outcomes for service users who require longer term support. PMID- 26897747 TI - 1001 Ways to run AutoDock Vina for virtual screening. AB - Large-scale computing technologies have enabled high-throughput virtual screening involving thousands to millions of drug candidates. It is not trivial, however, for biochemical scientists to evaluate the technical alternatives and their implications for running such large experiments. Besides experience with the molecular docking tool itself, the scientist needs to learn how to run it on high performance computing (HPC) infrastructures, and understand the impact of the choices made. Here, we review such considerations for a specific tool, AutoDock Vina, and use experimental data to illustrate the following points: (1) an additional level of parallelization increases virtual screening throughput on a multi-core machine; (2) capturing of the random seed is not enough (though necessary) for reproducibility on heterogeneous distributed computing systems; (3) the overall time spent on the screening of a ligand library can be improved by analysis of factors affecting execution time per ligand, including number of active torsions, heavy atoms and exhaustiveness. We also illustrate differences among four common HPC infrastructures: grid, Hadoop, small cluster and multi-core (virtual machine on the cloud). Our analysis shows that these platforms are suitable for screening experiments of different sizes. These considerations can guide scientists when choosing the best computing platform and set-up for their future large virtual screening experiments. PMID- 26897749 TI - Erratum to: TERT promoter hot spot mutations are frequent in Indian cervical and oral squamous cell carcinomas. PMID- 26897746 TI - Diapause as escape strategy to exposure to toxicants: response of Brachionus calyciforus to arsenic. AB - Invertebrate organisms commonly respond to environmental fluctuation by entering diapause. Production of diapause in monogonont rotifers involves a previous switch from asexual to partial sexual reproduction. Although zooplankton have been used in ecotoxicological assays, often their true vulnerability to toxicants is underestimated by not incorporating the sexual phase. We experimentally analyzed traits involved in sexual reproduction and diapause in the cyclically parthenogenetic freshwater rotifer, Brachionus calyciflorus, exposed to arsenic, a metalloid naturally found in high concentrations in desert zones, focusing on the effectiveness of diapause as an escape response in the face of an adverse condition. Addition of sublethal concentrations of arsenic modified the pattern of diapause observed in the rotifer: investment in diapause with arsenic addition peaked earlier and higher than in non-toxicant conditions, which suggests that sexual investment could be enhanced in highly stressed environmental conditions by increased responsiveness to stimulation. Nevertheless, eggs produced in large amount with arsenic, were mostly low quality, and healthy-looking eggs had lower hatching success, therefore it is unclear whether this pattern is optimum in an environment with arsenic, or if rather arsenic presence in water bodies disturbs the optimal allocation of offspring entering diapause. We observed high accumulation of arsenic in organisms exposed to constant concentration after several generations, which suggests that arsenic may be accumulated transgenerationally. The sexual phase in rotifers may be more sensitive to environmental conditions than the asexual one, therefore diapause attributes should be considered in ecotoxicological assessment because of its ecological and evolutionary implications on lakes biodiversity. PMID- 26897748 TI - C6 ceramide sensitizes the anti-hepatocellular carcinoma (HCC) activity by AZD 8055, a novel mTORC1/2 dual inhibitor. AB - Aberrant activation of mammalian target of rapamycin (mTOR) plays pivotal roles in promoting hepatocellular carcinoma (HCC) tumorigenesis and chemoresistance. Here, we tested the potential anti-HCC activity by a novel mTOR complex 1/2 (mTORC1/2) dual inhibitor AZD-8055 and, more importantly, the potential AZD-8055 sensitization effect by a cell-permeable short-chain ceramide (C6). We showed that AZD-8055 mainly exerted moderate cytotoxic effect against a panel of HCC cell lines (HepG2, Hep3B, and SMMC-7721). Co-treatment of C6 ceramide remarkably augmented AZD-8055-induced HCC cytotoxicity. Meanwhile, C6 ceramide dramatically potentiated AZD-8055-induced HCC cell apoptotic death. Further studies demonstrated that AZD-8055 and C6 ceramide synergistically induced anti-survival and pro-apoptotic activity in primary cultured human HCC cells, but not in the non-cancerous human hepatocytes. Signaling studies showed that AZD-8055 and C6 ceramide synergistically suppressed Akt-mTOR complex 1/2 cascade activation. In vivo, AZD-8055 oral administration suppressed HepG2 hepatoma xenograft growth in nude mice, while moderately improving mice survival. Its anti-tumor activity was dramatically potentiated with co-administration of a liposome-packed C6 ceramide. Together, these results demonstrate that concurrent targeting mTORC1/2 by AZD 8055 exerts anti-tumor ability in preclinical HCC models, and its activity is further sensitized with co-administration of C6 ceramide. PMID- 26897750 TI - Rab23 is overexpressed in human astrocytoma and promotes cell migration and invasion through regulation of Rac1. AB - Rab23 overexpression has been implicated in several human cancers. However, its biological roles and molecular mechanism in astrocytoma have not been elucidated. The aim of this study is to explore clinical significance and biological roles of Rab23 in astrocytoma. We observed negative Rab23 staining in normal astrocytes and positive staining in 39 out of 86 (45 %) astrocytoma specimens using immunohistochemistry. The positive rate of Rab23 was higher in grades III and IV (56.5 %, 26/46) than grades I + II astrocytomas (32.5 %, 13/40, p < 0.05). Transfection of Rab23 plasmid was performed induced A172 cell proliferation, colony formation, invasion, and migration, while Rab23 depletion with siRNA reduced these abilities of U87 cells. In addition, we found that Rab23 transfection upregulated while its depletion reduced Rac1 activity. Treatment of transfected cells with a Rac1 inhibitor decreased Rac1 activity and invasion. In conclusion, Rab23 serves as an important oncoprotein in human astrocytoma by regulating cell invasion and migration through Rac1 activity. PMID- 26897744 TI - Inflammation as a Therapeutic Target for Diabetic Neuropathies. AB - Diabetic neuropathies (DNs) are one of the most prevalent chronic complications of diabetes and a major cause of disability, high mortality, and poor quality of life. Given the complex anatomy of the peripheral nervous system and types of fiber dysfunction, DNs have a wide spectrum of clinical manifestations. The treatment of DNs continues to be challenging, likely due to the complex pathogenesis that involves an array of systemic and cellular imbalances in glucose and lipids metabolism. These lead to the activation of various biochemical pathways, including increased oxidative/nitrosative stress, activation of the polyol and protein kinase C pathways, activation of polyADP ribosylation, and activation of genes involved in neuronal damage, cyclooxygenase 2 activation, endothelial dysfunction, altered Na(+)/K(+)-ATPase pump function, impaired C-peptide-related signaling pathways, endoplasmic reticulum stress, and low-grade inflammation. This review summarizes current evidence regarding the role of low-grade inflammation as a potential therapeutic target for DNs. PMID- 26897751 TI - Roles of microRNA-124a and microRNA-30d in breast cancer patients with type 2 diabetes mellitus. AB - The aim of the study is to explore roles of microRNA (miR)-124a and miR-30d in breast cancer (BC) patients with type 2 diabetes mellitus (T2DM). A total of 144 cases of confirmed diagnosed BC with T2DM, T2DM, BC, or healthy people were enrolled. Among them, BC patients with T2DM were regarded as the experiment group (n = 36), patients with T2DM as the Dm group (n = 36), patients with BC as the Bc group (n = 36), and healthy subjects as the healthy group (n = 36). The fasting insulin resistance index, glycosylated hemoglobin, and estradiol were measured. MiR-124a and miR-30d expressions were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The insulin resistance index was significantly higher in the experiment group compared to the other three groups (all P < 0.05). The glycated hemoglobin was in a normal range in the Bc group and healthy group, but was higher in the experiment group and the Bc group compared to that in the healthy group (both P < 0.05). The serum estradiol level was obviously higher in the Bc group compared with that in the Dm group and the experiment group (both P < 0.05). The expressions of miR-124a and miR-30d were positively correlated with insulin resistance index, BMI and glycosylated hemoglobin (miR-124a r = 0.659, r = 0.785, and r = 0.862; miR-30d r = 0.742, r = 0.805, r = 0.765; all P < 0.001). Insulin resistance index was an independent factor for expressions of miR124-a and miR-30d. MiR-124a and miR-30d were correlated with insulin resistance and development of BC with T2DM. Although the mechanism is not clear, miR-124a and miR-30d potentially may be used as therapeutic targets and prognostic markers for BC patients with T2DM. PMID- 26897754 TI - Tissue penetration and exposure of cefepime in patients with diabetic foot infections. PMID- 26897755 TI - Synergistic activity of antibiotics combined with ivermectin to kill body lice. AB - Ivermectin and doxycycline have been found to be independently effective in killing body lice. In this study, 450 body lice were artificially fed on a ParafilmTM membrane with human blood associated with antibiotics (doxycycline, erythromycin, rifampicin and azithromycin) alone and in combination with ivermectin. Fluorescence in situ hybridisation and spectral deconvolution were performed to evaluate bacterial transcriptional activity following antibiotic intake by the lice. In the first series, a lethal effect of antibiotics on lice was observed compared with the control group at 18 days (log-rank test, P<=10( 3)), with a significant difference between groups in the production of nits (P=0.019, Kruskal-Wallis test). A high lethal effect of ivermectin alone (50ng/mL) was observed compared with the control group (log-rank test, P<=10( 3)). Fluorescence of bacteriocytes in lice treated with 20MUg/mL doxycycline was lower than in untreated lice (P<0.0001, Kruskal-Wallis test). In the second series with antibiotic-ivermectin combinations, a synergistic lethal effect on treated lice (log-rank test, P<10(-6)) was observed compared with the control group at 18 days, associated with a significant decrease in the production of nits (P<=0.001, Kruskal-Wallis test). Additionally, survival of lice in the combination treatment groups compared with ivermectin alone was significant (log rank test, P=0.0008). These data demonstrate that the synergistic effect of combinations of antibiotics and ivermectin could be used to achieve complete eradication of lice and to avoid selection of a resistant louse population. PMID- 26897753 TI - Combined Cerebellar Proton MR Spectroscopy and DWI Study of Patients with Friedreich's Ataxia. AB - Friedreich's ataxia (FRDA) is the commonest autosomal recessive ataxia, caused by GAA triplet expansion in the frataxin gene. Neuropathological studies in FRDA demonstrate that besides the primary neurodegeneration of the dorsal root ganglia, there is a progressive atrophy of the cerebellar dentate nucleus. Diffusion-weighted imaging (DWI) detected microstructural alterations in the cerebellum of FRDA patients. To investigate the biochemical basis of these alterations, we used both DWI and proton MR spectroscopy (1H-MRS) to study the same cerebellar volume of interest (VOI) including the dentate nucleus. DWI and 1H-MRS study of the left cerebellar hemisphere was performed in 28 genetically proven FRDA patients and 35 healthy controls. In FRDA mean diffusivity (MD) values were calculated for the same 1H-MRS VOI. Clinical severity was evaluated using the International Cooperative Ataxia Rating Scale (ICARS). FRDA patients showed a significant reduction of N-acetyl-aspartate (NAA), a neuroaxonal marker, and choline (Cho), a membrane marker, both expressed relatively to creatine (Cr), and increased MD values. In FRDA patients NAA/Cr negatively correlated with MD values (r = -0.396, p = 0.037) and with ICARS score (r = -0.669, p < 0.001). Age normalized NAA/Cr loss correlated with the GAA expansion (r = -0.492, p = 0.008). The reduced cerebellar NAA/Cr in FRDA suggests that neuroaxonal loss is related to the microstructural changes determining higher MD values. The correlation between NAA/Cr and the severity of disability suggests that this biochemical in vivo MR parameter might be a useful biomarker to evaluate therapeutic interventions. PMID- 26897757 TI - The effects of sample size on population genomic analyses--implications for the tests of neutrality. AB - BACKGROUND: One of the fundamental measures of molecular genetic variation is the Watterson's estimator (theta), which is based on the number of segregating sites. The estimation of theta is unbiased only under neutrality and constant population growth. It is well known that the estimation of theta is biased when these assumptions are violated. However, the effects of sample size in modulating the bias was not well appreciated. RESULTS: We examined this issue in detail based on large-scale exome data and robust simulations. Our investigation revealed that sample size appreciably influences theta estimation and this effect was much higher for constrained genomic regions than that of neutral regions. For instance, theta estimated for synonymous sites using 512 human exomes was 1.9 times higher than that obtained using 16 exomes. However, this difference was 2.5 times for the nonsynonymous sites of the same data. We observed a positive correlation between the rate of increase in theta estimates (with respect to the sample size) and the magnitude of selection pressure. For example, theta estimated for the nonsynonymous sites of highly constrained genes (dN/dS < 0.1) using 512 exomes was 3.6 times higher than that estimated using 16 exomes. In contrast this difference was only 2 times for the less constrained genes (dN/dS > 0.9). CONCLUSIONS: The results of this study reveal the extent of underestimation owing to small sample sizes and thus emphasize the importance of sample size in estimating a number of population genomic parameters. Our results have serious implications for neutrality tests such as Tajima D, Fu-Li D and those based on the McDonald and Kreitman test: Neutrality Index and the fraction of adaptive substitutions. For instance, use of 16 exomes produced 2.4 times higher proportion of adaptive substitutions compared to that obtained using 512 exomes (24% vs 10 %). PMID- 26897756 TI - Repetitive Transcranial Magnetic Stimulation: a Novel Approach for Treating Oropharyngeal Dysphagia. AB - In recent years, repetitive transcranial magnetic stimulation, a technique used to produce human central neurostimulation, has attracted increased interest and been applied experimentally in the treatment of dysphagia. This review presents a synopsis of the current research for the application of repetitive transcranial magnetic stimulation (rTMS) on dysphagia. Here, we review the mechanisms underlying the effects of rTMS and the results from studies on both healthy volunteers and dysphagic patients. The clinical studies on dysphagia have primarily focussed on dysphagia post-stroke. We discuss why it is difficult to draw conclusions for the efficacy of this neurostimulation technique, given the major differences between studies. The intention here is to stimulate potential research questions not yet investigated for the application of rTMS on dysphagic patients prior to their translation into clinical practice for dysphagia rehabilitation. PMID- 26897760 TI - Zika virus infection: global update on epidemiology and potentially associated clinical manifestations. PMID- 26897761 TI - Risk communication - A moving target in the fight against infectious hazards and epidemics. PMID- 26897758 TI - Depth of cure of bulk fill composites with monowave and polywave curing lights. AB - PURPOSE: To measure and compare the depth of cure (DOC) of two bulk fill resin composites using a monowave and polywave light curing unit (LCU) according to ISO 4049 and using custom tooth molds. METHODS: The DOC of Tetric Evoceram Bulk Fill and Filtek Bulk Fill Posterior were measured using a monowave LED LCU (Elipar S10) and a polywave LED LCU (Bluephase G2). Metal molds were used to fabricate 10 mm long DOC specimens (n = 10) according to ISO 4049. Uncured composite material was scraped away with a plastic instrument and half the length of remaining composite was measured as the DOC. Custom tooth molds were fabricated by preparing > 10 mm long square- shaped (4 x 4 mm) holes into the mesial/distal surfaces of extracted human molars. Resin composite was placed into one end of the prepared tooth and light polymerized. Uncured resin composite was removed from the opposite side from which the tooth was irradiated and the tooth was sectioned mesio-distally. Half the length of remaining cured composite was measured as the DOC. Data were analyzed by three-way ANOVA (alpha = 0.05) for factors material, LCU, and mold. RESULTS: The main effect LCU was not significant (P = 0.58). The interaction effect between material x mold was significant (P = 0.0001). The DOC of the composites differed significantly only with the stainless steel mold in which Tetric Evoceram Bulk Fill showed a deeper DOC than Filtek Bulk Fill Posterior (4.03 +/- 0.14 vs 3.56 +/- 0.38 mm, P < 0.0001). PMID- 26897759 TI - [New therapeutic strategy for head-and-neck neoplasms--Molecular target therapy]. PMID- 26897752 TI - Circulating tumor cell technologies. AB - Circulating tumor cells, a component of the "liquid biopsy", hold great potential to transform the current landscape of cancer therapy. A key challenge to unlocking the clinical utility of CTCs lies in the ability to detect and isolate these rare cells using methods amenable to downstream characterization and other applications. In this review, we will provide an overview of current technologies used to detect and capture CTCs with brief insights into the workings of individual technologies. We focus on the strategies employed by different platforms and discuss the advantages of each. As our understanding of CTC biology matures, CTC technologies will need to evolve, and we discuss some of the present challenges facing the field in light of recent data encompassing epithelial-to mesenchymal transition, tumor-initiating cells, and CTC clusters. PMID- 26897762 TI - [Function sparing surgery for pharyngeal neoplasms]. PMID- 26897763 TI - [Robotic surgery in the field of otorhinolaryngology]. PMID- 26897764 TI - [Intensity modulated radiotherapy]. PMID- 26897766 TI - [The pathologist is not a bad doctor, he just arrives too late!]. PMID- 26897765 TI - [Particle beam radiotherapy]. PMID- 26897767 TI - [Prevent a bite--the bite-prevention project between child and dog]. PMID- 26897768 TI - [The special picture: Out of Africa]. PMID- 26897769 TI - [Advertising law and practice descriptions]. PMID- 26897770 TI - [Intermittent upward fixation of the patella in 12 cows: A retrospective study of treatment and long-term prognosis]. AB - This retrospective study investigated possible risk factors for intermittent upward fixation of the patella and the outcome of medial patellar desmotomy in 12 cows. All but one young cow had distinctive clinical signs, which usually started in the periparturient period. Medial patellar desmotomy led to normalisation of the stride in 10 cows but did not improve the condition of the young cow. Another cow developed instability and signs of lateral patellar luxation in the affected stifle and was euthanized. The 10 cows that were operated successfully remained in the long term free of symptoms. Medial patellar desmotomy is a suitable treatment for upward patellar fixation in cattle but should be reserved for cows with typical clinical signs. The medial patellar ligament should be cut 4 to 6 cm proximal to its insertion on the tibia to minimise the risk of injury to the middle patellar ligament. PMID- 26897771 TI - Intestinal epidermoid cyst in a cat. AB - A 3-year-old cat was presented with anorexia and vomiting. Palpation revealed a caudal abdominal mass. Ultrasound and explorative abdominal surgery revealed a cystic mass in the jejunum. Histopathologic findings were consistent with an epidermoid cyst. The cyst was likely of congenital origin, since the cat had not undergone previous abdominal surgery, and gradually grew to reach a size that caused intestinal obstruction. Extrapolating from findings in people, intestinal epidermoid cysts are considered benign with a good long-term prognosis when completely excised. PMID- 26897772 TI - An unusual case of intestinal leiomyositis in a Bernese mountain dog. AB - A 1-year-old, female Bernese mountain dog was presented to the Veterinary Teaching Hospital of Turin University with a 3-month history of weight loss, intermittent anorexia, vomiting, constipation, and abdominal distension. Full thickness biopsies from the stomach, duodenum, jejunum and ileum were collected for histological and immunohistochemical examination. Microscopic lesions displayed severe diffuse degeneration and loss of leiomyocytes, with lymphocytic leiomyositis, fibroplasia, angiogenesis, severe diffuse neuronal atrophy, and ganglioneuritis in the myenteric (Auerbach's) plexus. A diagnosis of chronic idiopatic intestinal pseudo-obstruction was made. Response to immunosuppressive therapy was poor and the dog was humanely euthanized. Unique findings were mononuclear infiltration composed predominantly of B-cell, angiogenesis and weak immunoreactivity for neuron-specific enolase. PMID- 26897773 TI - [93 YEARS OF CLINICAL EMPATHY, STATE-OF-THE-ART MEDICINE AND RESEARCH EXCELLENCE]. AB - This issue of Harefuah is devoted to articles and reviews written by the medical staff of Bnai Zion Medical Center in Haifa. Celebrating 93 years since its inception, Bnai Zion Medical Center is home to the oldest public hospital in Haifa, and a founding affiliate of the Technion's Faculty of Medicine. Known for its centers of excellence and the impactful clinical and basic research developed, the hospital has a reputation for state-of-the-art medicine, both conventional and complementary. Bnai Zion prides itself as an innovation leader in medical and nursing education, with its staff's empathetic and personalized approach to patient care, and the center's dedication to applying emotional intelligence to medicine. PMID- 26897774 TI - [MULTICENTER EXPERIENCE WITH ALLIUM URETERAL STENT FOR THE TREATMENT OF URETERAL STRICTURE AND FISTULA]. AB - INTRODUCTION: Chronic ureteral stricture and ureteral fistula are treated with urinary diversion using percutaneous nephrostomy or double pigtail stent. Both of these techniques require replacement of the tube every few months in order to prevent encrustations and obstruction. OBJECTIVES: To report the long-term efficacy of the new Allium Ureteral Stent (URS) in the treatment of ureteral stricture and fistula. METHODS: The Allium URS is a newly-developed ureteral stent made of nickel-titanium (Nitinol), which is inserted in a small diameter and spontaneously expands into and preserves a large-caliber. The stent is coated with a biochemical co-polymer which prevents tissue ingrowth and incrustations. The stent is inserted antegradely or retrogradely with intraoperative x-ray guidance after dilation of the stricture. The Allium URS stent was inserted into 107 ureters of 92 patients in 5 different centers worldwide; 69 patients carried a percutaneous nephrostomy before the procedure and 38 patients had a ureteral stent. The etiologies underlying the strictures were: gynecological cancer (with or without irradiation), bladder cancer, iatrogenic stricture, ureteroileal stenosis, stricture following uretero-pelvic junction obstruction repair and iatrogenic ureteral fistula. RESULTS: During a mean follow-up of 27 months, only one stent was obstructed after eleven-indwelling months; 21 patients died of their primary disease carrying the stent. Stent migration was seen in 11 patients within 8 months after its insertion, and these stents were removed. In 4 patients with early stent migration, the stents were replaced. In 18 patients the stents were removed as planned after one year of indwelling time, and these patients were asymptomatic in a follow-up period of up to 59 months. CONCLUSION: The results of our study show that the use of Allium URS for the treatment of ureteral strictures is feasible, safe and effective. The relative ease of its insertion could encourage its use in a wide range of other indications. DISCUSSION: Due to its unique structure, the Allium URS is superior to the regular pigtail stents in the treatment of ureteral strictures. Stent migration was seen in only 10.7% of the patients, mainly in patients with stricture of the mid-ureter. SUMMARY: The use of the Allium URS stent in the treatment of proximal and distaL ureteral strictures is safe and effective. PMID- 26897775 TI - [OPIATES USE IN VERY-LOW-BIRTH-WEIGHT INFANTS--CALL FOR CAUTION]. AB - BACKGROUND: Very-low-birth-weight (VLBW) infants are occasionally treated with opiates for sedation and pain relief. OBJECTIVE: To study the short term outcomes of VLBW infants treated with opiates. METHODS: We conducted a retrospective study of all VLBW infants born during the period 2006-2010; 45 were treated with opiates (41 fentanyl continuous IV drip and 4 IV morphine prn); 114 served as controls. RESULTS: In the univariate analysis, VLBW infants treated by opiates had significantly lower Gestational Age (GA) (28.3 +/- 2.4 vs. 30.3 +/- 2.1 weeks) and BW (1012 +/- 299 vs. 1204 +/- 219 grams] and required longer periods of ventilatory support (30.3 +/- 21.0 vs. 7.7 +/- 12.0 days) and oxygen supplementation (40.4 +/- 40.3 vs. 7.7 +/- 17.3 days). They had significantly more intraventricular hemorrhage (IVH), patent ductus arteriosus (PDA), late onset infections, necrotizing enterocolitis (NEC and bronchopulmonary dysplasia (BPD). Time to reach full enteral (32.5 +/- 22.1 vs. 15.6 +/- 6.1 days) and full oral (64.6 +/- 25.0 vs. 42.0 +/- 20.7 days) feedings and length of stay (89.6 +/- 37.1 vs. 53.7 +/- 20.8 days) were significantly longer. In multivariate analysis, after controlling for GA and BW, opiates remained significantly associated only with PDA and longer ventilatory support and time to full enteral feeding. CONCLUSION: The use of opiates in VLBW infants may be associated with short term morbidities. Thus, opiates should be used with caution in this age group, and alternative approaches for sedation or pain relief should be considered. Randomized controlled studies are warranted to support our findings. PMID- 26897776 TI - [COCHLEAR IMPLANTATION IN ELDERLY INDIVIDUALS: INSIGHTS BASED ON A RETROSPECTIVE EVALUATION]. AB - INTRODUCTION: In old age, the typical decline in temporal processing, auditory memory, speed of information processing, and ability to filter out irrelevant competing auditory input lead to deterioration in speech perception. This thereby broadens the target population for cochlear implantation among elderly individuals with severe-to-profound hearing loss. These features also raise concern regarding cochlear implant (CI) fitting and outcomes. AIM: To establish expectations from CI in older individuals. METHODS: This is a retrospective case review of 20 individuals with severe or severe-to-profound hearing loss, aged 60 or older (mean, 66.6 +/- 5.25; range, 60-81 at the time of CI. Evaluation included speech-perception tests and the Glasgow Benefit Inventory (GBI) for testing quality of life. RESULTS: Between pre- and post-implantation, mean group values improved from 18.6% to 55.5%, from 37.2% to 84.5%, and from 11.2% to 60.5%, respectively, on the above speech-perception tests. No major postoperative complications were observed. The device was used consistently by all but one patient. GBI revealed improvement on all subscales. CONCLUSIONS: After implantation speech perception improved, there were no major post-CI complications, and post-implantation vertigo was less significant than expected in this age group. These results diminish concerns regarding CI in elderly individuals. PMID- 26897777 TI - [SPONTANEOUS BACTERIAL EMPYEMA--A RARE BUT IMPORTANT COMPLICATION OF HEPATIC HYDROTHORAX IN CIRRHOTIC PATIENTS]. AB - Spontaneous bacterial empyema, a complication of hepatic hydrothorax in cirrhotic patients, is a rare but nevertheless important medical entity. The diagnosis, treatment and prognosis of spontaneous bacterial empyema differs from the "usual" empyema, and avoiding proper diagnosis or treatment delay may have far reaching consequences. We report on a patient who was diagnosed in our department with spontaneous bacterial empyema, review the main current literature on the subject and elaborate on the specific therapeutic considerations related to the case management. PMID- 26897778 TI - [CAN FOOD THICKENING IMPROVE THE ABILITY OF PREMATURE INFANTS TO ACQUIRE FULL ORAL FEEDING EARLIER? A PILOT STUDY]. AB - BACKGROUND: Acquiring oral feeding skills can take longer in preterm infants and can lengthen their hospital stay. OBJECTIVE: To study whether food thickening could improve preterm infants' ability to reach full oral feeding earlier. METHODS: This is a prospective randomized trial for which 15 infants were recruited upon showing signs of oral feeding readiness. Eight infants fed on human milk were controls. Of the 7 infants fed on formula, five infants were randomized to food thickening with corn flour starch and two infants were given another un-thickened control. RESULTS: Mean gestational age was 29.0 +/- 2.3 weeks and mean birth-weight was 1174 +/- 325 g. Food thickening had no effect on the time to reach full oral feeding (17.4 +/- 6.7 days with thickened formula vs. 18.0 +/- 7.0 on un-thickened formula and 12.1 +/- 9.5 on human milk) or on the length of stay (66.8 +/- 26.0 days vs. 52.5 +/- 17.7 and 56.2 +/- 25.3, respectivey). Multivariate analysis showed that time to full oral feeding and length of stay were only associated with gestational age or birth-weight and respiratory morbidity, as expressed in the number of ventilation and supplemental oxygen days. Weight gain was faster in those given thickened formula (36.0 +/- 7.1 g/day) compared to those on human milk (28.5 +/- 6.5 g/day). CONCLUSIONS: Food thickening with corn flour did not shorten the time to reach full oral feeding in preterm infants. This type of food thickening was associated with extra weight gain. Larger blinded prospective studies are needed to confirm our findings. PMID- 26897779 TI - [APPENDECTOMY FOR COMPLICATED APPENDICITIS IN CHILDREN--LAPAROSCOPIC OR OPEN?]. AB - INTRODUCTION: Laparoscopic appendectomy (LA) is widely accepted for simple appendicitis but it is still debatable in complicated cases (gangrenous or perforated appendicitis). AIM: The purpose of the present study was to evaluate the outcomes of LA versus open appendectomy (OA) in uncomplicated and complicated appendicitis in children. METHODS: A retrospective analysis of the clinical data of children (< 18 years old) who underwent LA and CA from 2008 to 2011 was performed. The incidental appendectomies were excluded. The patients were divided into four groups according to the severity of the disease (uncomplicated vs complicated) and by the surgical approach (LA vs OA). Data were compared with regard to demographic features, pre-operative, intra-operative and post-operative findings. MAIN RESULTS: A total of 335 children underwent urgent appendectomy during this period. The overall rate of perforated appendicitis was 26.9%; 143 patients (42.7%) underwent LA and 192 patients (57.3%) underwent CA. Operative times and complication rates did not differ significantly between LA and OA in either complicated to uncomplicated appendicitis; LOS was shorter in the uncomplicated group (2.14 +/- 0.17 vs 3.15 +/- 0.14, p < 0.01). Two patients from the uncomplicated group underwent conversions form LA to OA (conversion rate of 1.36%) because of intraoperative bleeding, and one patient in the OA-complicated group had a cecal injury. There were no mortalities in this group. CONCLUSIONS: Laparoscopic appendectomy for complicated appendicitis in children is feasible and safe, does not harbor any risks in comparison to the open traditional procedure, and allows the benefits of better view, flexible angle of approach and cosmesis. PMID- 26897780 TI - [ALPHA-1-ANTITRYPSIN ACTIVITY IN PATIENTS HOSPITALIZED FOR CELLULITIS]. AB - INTRODUCTION: Deficiency or impaired activity of alpha-1-antitrypsin (AAT), which neutralizes multiple proteolytic enzymes, such as collagenases and elastases may result in significant tissue autodigestion. Hence, AAT may have a role in the healing process in chronic and acute inflammation including skin infection, such as cellulitis. AIM: The aim of this study was to evaluate the role of AAT activity and inflammatory markers in patients with cellulitis. METHODS: The study included eleven consecutive patients (6 males and 5 females, mean age 68.5 +/- 4.5 years) who were hospitalized for cellulitis between 09/2009-02/2010. We analyzed tests results for C reactive protein (CRP), AAT level and activity that were obtained on admission (T1), 2 days after admission (T2) and 2 weeks after admission (T3). RESULTS: AAT levels were found to be within the normal range. AAT activity values were found to be within or above the normal range. The highest activity values were measured after 2 days of treatment and the lowest values were measured after 2 weeks of treatment. CRP values were highest on admission and lowest, as expected, after the end of treatment 2 weeks later. AAT activity values were significantly lower statistically in patients with unresolved cellulitis 2 weeks after treatment began. SUMMARY: AAT activity was significantly lower statistically in patients who suffered from slow resolving cellulitis 14 days after hospitalization. This possibly suggests a role AAT activity may have in the inflammation cascade in patients with cellulitis. Further studies are needed to evaluate the role of AAT activity in the inflammatory process. PMID- 26897781 TI - [THE WORLD EXPERIENCE OF THE PEDIATRIC INTESTINAL FAILURE PROGRAM: SUCCESSFUL OUTCOMES FROM INTESTINAL REHABILITATION]. AB - Management of children with short bowel syndrome is optimized by interdisciplinary coordination of parenteral and enteral nutrition support, medical management of associated complications, surgical lengthening procedures, and intestinal transplantation. Pediatric Intestinal Failure Centers were established in 14 pediatric hospitals throughout the United States and Canada and the Pediatric Intestinal Failure Consortium has been developed and is implementing prospective, multi-institutional studies to better define the specific aspects of intestinal failure management that optimize long-term outcomes. The published data from these studies suggest that intestinal failure in pediatric patients is quite treatable and provides further evidence that all infants at risk for intestinal failure should be treated aggressively and referred early to a dedicated intestinal rehabilitation center. Improved communication and integration with the transplant service have resulted in earlier assessment, decreased rates of transplantation, and decreased mortality from liver failure. The data presented demonstrates that a newly established intestinal failure program can achieve excellent survival in a cohort of chronically ill and complex pediatric cases that have historically been associated with substantial mortality. PMID- 26897782 TI - [IMMUNIZATIONS IN IMMUNOCOMPROMISED HOSTS--PRINCIPLES AND UPDATED RECOMMENDATIONS]. AB - The last decades have seen a marked increase in the number of immunocompromised patients. These patients are at higher risk for severe outcomes from infections, many of which are vaccine-preventable diseases. However, such complex cases raise several important issues of concern: 1. The administration of live vaccines to an immunocompromised patient may lead to adverse events and exacerbate the underlying condition? 2. Vaccines should preferably be administered prior to the planned immunosuppressive therapies. 3. Vaccination with inactivated vaccines may not ensure complete immune responses and may lead to lower and shorter protection rates depending on the extent of immunosuppression. 4. Should household contacts of immunocompromised patients receive vaccines? Which vaccines can be safely administered to household members? 5. Do clinicians have sufficient or updated information concerning the safety, efficacy and contraindications to vaccination of such at-risk patients? 6. Which vaccines can be safely administered to immunocompromised travelers to tropical destinations? The answers to those questions are multifaceted, and data on safety, immunogenicity, and efficacy of vaccines for immunocompromised populations are limited. This article summarizes the current recommendations for immunizations in immunocompromised patients, indications and potential adverse effects. PMID- 26897783 TI - [CHALLENGES IN THE DIAGNOSIS OF CUSHING'S SYNDROME IN THE MODERN ERA]. AB - Cushing's syndrome results from prolonged and excessive exposure to medically prescribed corticosteroids, or from excess endogenous cortisol secretion. When endogenous cortisol secretion is suspected, several screening tests are conducted in order to confirm or to rule out the diagnosis. In recent years, as the cut-off point of cortisol concentration on the 1 mg overnight dexamethasone suppression test was lowered, the prevalence of Cushing's syndrome has increased, and more cases of mild syndromes, with negative results on one or more screening tests, have increasingly been reported. In this paper, we will describe the various screening tests used for Cushing's syndrome, and will discuss their degree of sensitivity in the diagnosis of mild cases. We conclude that, in cases of mild syndromes, the sensitivity of some tests appears to be notably lower than has been reported. Until recently, the major challenge has been to distinguish between pseudo-Cushing's states and Cushing's syndrome. Today, however, the challenge has become to avoid misdiagnosis of mild cases, presenting with normal results on some screening tests. The sensitivity of urinary free cortisol seems to be lower than previously reported. Therefore, we recommend not to rely solely on this test in ruling out Cushing's syndrome. PMID- 26897784 TI - [PRIMARY HEADACHE IN CHILDREN AND ADOLESCENTS--DIAGNOSIS AND TREATMENT]. AB - BACKGROUND: Primary headaches are one of the most common disorders of childhood, with migraine and tension type headaches (TTHs) being the most frequent ones. In spite of their prevalence, there is paucity of knowledge regarding the underlying pathophysiological mechanisms that cause headaches and regarding the unique aspects of headaches in children and adolescents. AIM: To review the literature and summarize the knowledge regarding clinical features, diagnosis and management of primary headache in children and adolescents, mainly migraine and TTH. RESULTS AND CONCLUSIONS: Most of our current knowledge regarding primary headaches in children and adolescents is driven from extrapolations from studies that were conducted with adult patients. Therefore, it needs to be validated for the different age groups. Migraines may be diagnosed effectively based on the 2nd edition of the International Classification of Headache Disorders (ICHD-II), however, TTH is diagnosed mainly by the absence of features found in other headache types. Treatment strategies for primary headaches vary according to patient's age, family structure, culture and beliefs, headache diagnosis, and based on the disability the headache imposes on the patient's daily living. It was shown that a multidisciplinary approach, that includes continuing counseling, education, and reassurance, in combination with pharmacological and non pharmacological treatment, is an effective strategy for children and adolescents suffering from primary headaches. Further studies are needed to enrich our knowledge about the pathophysiological mechanisms that cause headaches in children and adolescents and to develop efficient strategies to alleviate their burden. PMID- 26897786 TI - Change, anyone?. PMID- 26897785 TI - [EPIDIDYMO-ORCHITIS IN PREPUBERTAL CHILDREN--PREVALENCE, ETIOLOGY, SUGGESTED DIAGNOSIS ALGORITHM]. AB - Gonadal inflammation (GI) is a common disease that may affect prepubertal boys. Neonates may suffer from bacterial infection due to congenital or aging processes affecting the urinary tract. This inflammatory process is also prevalent in prepubertal boys. However, in this group, the etiology, the needed imaging modalities and proper management have not yet been clearly defined. This manuscript will systematically review the various etiologies causing GI in pre pubertal boys, discuss the proper imaging needed, and image interpretation and will provide treatment and follow-up recommendations. PMID- 26897787 TI - Blepharoptosis: Clinical Presentation, Diagnosis, and Treatment. PMID- 26897788 TI - Visual Field Deficits After Eye Loss: What Do Monocular Patients (Not) See?. AB - Losing an eye presents physical and visual as well as emotional challenges to patients, but few health care providers understand the challenges of monocularity. Ocularists can play an important role in helping patients adjust, including maximizing the visual field despite prosthetics and eyeglasses and giving advice for monocular living. PMID- 26897789 TI - It Takes Vision to Have Cybersight. PMID- 26897791 TI - Get Certified Today! PMID- 26897790 TI - What Motivates Patients to Return to the Office for Cosmetic Periorbital Filling: Is it the Result or the Experience? PMID- 26897792 TI - OCT Challenge. PMID- 26897793 TI - Shawn M. Herman, RN, BSN. PMID- 26897794 TI - French Lick... PMID- 26897795 TI - Average in America. PMID- 26897796 TI - When Helping Hurts. PMID- 26897797 TI - The Healthy Indiana Plan: Indiana's complete solution to better health for Hoosiers. PMID- 26897798 TI - Sow and Reap. PMID- 26897799 TI - Why French Lick? PMID- 26897800 TI - Transition planning your practice: 5 items to consider. PMID- 26897801 TI - Common Questions for Dentists Considering a Transition. PMID- 26897802 TI - Dental Stem Cell Banking and Use In Regenerative Medicine. A Case Report. PMID- 26897804 TI - In Medio Stat Virtis. PMID- 26897803 TI - Fixtures in the Bone. PMID- 26897805 TI - Pharmacology and Folklore: The Arsenic Eaters of Styria. PMID- 26897806 TI - Pharmacy and Chemistry in the Eighteenth Century. What Lessons for the History of Science? PMID- 26897807 TI - Valve Replacement for Moderate Aortic Stenosis in Octogenarians Undergoing Revascularization. AB - BACKGROUND AND AIM OF THE STUDY: The study aim was to determine if the 'prophylactic' replacement of the aortic valve to treat moderate aortic valve stenosis (AS) in octogenarians undergoing cardiac surgery for coronary disease can influence outcome, and is also justified. METHODS: In a retrospective analysis of octogenarians operated on at the authors' center between 1998 and 2012, the patients were allocated to: Group I, isolated coronary artery bypass graft surgery (CABG; n = 159); Group II, combined CABG and aortic valve replacement (AVR) with the primary indication for surgery being severe AS (n = 156); and Group III, combined AVR +CABG with coronary disease being the primary indication and concomitant 'prophylactic' AVR (n = 34). RESULTS: The hospital mortality for octogenarians undergoing CABG+AVR was 8% compared to 2% for isolated CABG (p = 0.02). Survival at one year was higher in the isolated CABG group (94%) than in the CABG+AVR group (86%) (p = 0.01), but was no different at five years. Mortality according to AVR indication was similar (Group II 8% versus Group III 9%), as was one- and five-year survival. Group III had a higher preoperative co-morbid risk profile, including logistic EuroSCORE 21.7% versus 18% in Group II (p = 0.05), more recent myocardial infarctions, previous percutaneous interventions, peripheral vascular disease, and poor left ventricular function. Long-term symptomatic relief was excellent in Group III. Patients whose predominant disease profile was ischemic (Groups I and III) had a higher long-term risk of recurrent angina and stroke. CONCLUSION: In-hospital mortality is higher for octogenarians undergoing CABG+AVR compared to those undergoing isolated CABG. In the present study, a 'prophylactic' AVR was justified in patients with moderate AS, and their increased mortality (versus isolated CABG) was congruent with a higher preoperative co-morbid risk profile. Excellent long- term symptom-free survival further justifies 'prophylactic' AVR in octogenarians undergoing CABG with coexistent moderate AS. PMID- 26897808 TI - Aortic Annulus Diameter Affects Durability of the Repaired Bicuspid Aortic Valve. AB - BACKGROUND AND AIM OF THE STUDY: An investigation was made as to whether the preoperative aortic annular diameter affects the durability of bicuspid aortic valve (BAV) repair in patients who had undergone concomitant root stabilization with subcommissural annuloplasty (SCA) compared to valve-sparing root reimplantation (VSRR). METHODS: Among a retrospective review of 74 patients who underwent BAV repair between 2005 and 2012,42 had SCA and 32 had VSRR. RESULTS: The preoperative annulus was similar in the two groups (29 +/- 3 mm for SCA; 30 +/- 4 mm for VSRR, p = 0.3). Postoperative aortic insufficiency (AI) grade > or = 1+ was 100%, but five-year freedom from Al grade >1+ was lower in the SCA group (62 +/- 10% versus 92 +/- 6%, p = 0.02). On univariate analysis, a preoperative annulus 28 mm was predictive of recurrent Al grade >1+ in the SCA group (odds ratio 17.1, p = 0.05), but not in the VSRR group (3.31, p = 0.1). Consequently, SCA patients were evaluated by annular diameter 28 mm (n = 26) versus < or = 27 mm (n = 16). Five-year freedom from AI grade >1+ was lower for the 28 mm SCA subgroup (52 +/- 10% versus +/-3 +/- 6%, p = 0.02). Given this difference between the SCA subgroups, Al grade >1+ in the 28 mm SCA subgroup was compared to VSRR patients with annulus 28 mm ( 28 mm VSRR subgroup, n = 23). The five-year freedom from AI grade >1+ was significantly higher in the 28 mm VSRR subgrou+/- (86 +/- 10% versus 52 +/- 10%, p = 0.02), but simila < or = Sr in the 27 27 m< or = SCA and 527 mm VSRR subgroups (93 +/- 6% versus 100%, p = 0.4). CONCLUSION: For BAV patients with a preoperative aortic annulus 28 mm, SCA results in inferior midterm outcomes. VSRR or alternative annular stabilization techniques should be considered PMID- 26897809 TI - Direct Aortic Access Transcatheter Aortic Valve Replacement: Three-Dimensional Computed Tomography Planning and Real-Time Fluoroscopic Image Guidance. AB - BACKGROUND AND AIM OF THE STUDY: Direct aortic access for transcatheter aortic valve replacement (DA-TAVR) is an important alternative approach in patients with hostile ileo-femoral vessels. Planning the transaortic puncture site and an 'ideal' trajectory towards the annulus plane is important for safe and successful valve implantation. The feasibility of three-dimensional (3D) planning and real time fluoroscopic image guidance for DA-TAVR was evaluated using pre-procedural multi-detector computed tomography (MDCT) and intra-procedural Dyna CT co registration approaches. METHODS: Between May 2012 and August 2014, a total of 44 patients (40 mini-sternotomies, four mini-thoracotomies) was selected for DA-TAVR using the authors' MDCT-Dyna CT co-registration approach (32 CoreValve, 12 SAPIEN). Pre-procedural contrast-enhanced multi-slice CT (MSCT) and intra- procedural non-contrast Dyna CT images were co-registered based on cardiac outline and aortic root calcifications. Using a prototype software, the aortic root was segmented and relevant landmarks identified automatically. The intersection of a virtual perpendicular trajectory from the annulus with the greater curvature of the aorta was marked as the planned DA puncture site. The planned DA puncture site, trajectory and relevant landmarks were overlaid onto real-time fluoroscopic images for image guidance during DA-TAVR. RESULTS: Real time fluoroscopic overlay of planned trajectory was feasible in all 44 cases of DA-TAVR. The mean 2D projection distance error between the actual and planned aortic puncture sites was 1.60 +/- 1.1 cm. The mean angular difference error (measure of co-axiality) between actual and planned DA trajectory was 11.86 +/- 9.3. Errors in distance and co-axiality were lower with the mini-thoracotomy than with the mini-sternotomy approach. The Multi-Slice CT (MSCT)-Dyna CT co registration technique resulted in significantly less contrast usage, and trended towards shorter fluoroscopy and operative times. There was also a trend towards a reduction in acute kidney injury, but no difference was identified in the degree of paravalvular regurgitation or mortality. CONCLUSION: 3D access planning and real-time image guidance for DA-TAVR is feasible using an MDCT/non-contrast Dyna CT image co-registration-based approach. Such image co-registration strategies improve the accuracy of case planning and safety of valve deployment with a direct aortic approach. Further studies are necessary to determine if these enhancements translate into an improvement in clinical outcomes. PMID- 26897810 TI - Short-Term Outcomes with Direct Aortic Access for Transcatheter Aortic Valve Replacement. AB - BACKGROUND AND AIM OF THE STUDY: Transcatheter aortic valve replacement (TAVR) requires a safe route of access to the aortic valve. A direct aortic route has been used as alternate access approach in patients where ileo-femoral access is unsafe due to size, calcification and/or tortuosity. The study aim was to review the authors' results obtained with a direct aortic (DA) TAVR, examining in particular the safety and effectiveness of this approach. METHODS: A retrospective analysis was performed of all prospectively collected TAVR data from January 2011 to March 2015 at the authors' institution. DA-TAVRs were performed using either an upper mini- sternotomy (MST) into the second right intercostal space, or via a right anterior mini-thoracotomy (RAT) at the second intercostal space. The choice between MST and RAT approaches was made by the surgeon, based on aortic imaging, patent bypass grafts and pulmonary function. Both, Medtronic CoreValve and Edwards SAPIEN devices were used. All relevant perioperative and clinical outcomes were collected based on Valve Academic Research Consortium 2 (VARC-2) definitions. Median numerical values were used. RESULTS: Seventy-eight consecutive patients underwent DA-TAVR with 100% intraoperative survival and 92% 30-day survival. The procedural success was 97%. The majority of patients (79%) underwent DA-TAVR with the Medtronic CoreValve, via MST (92%). All patients were classified either as extreme (74%) or high risk (26%) for surgical aortic valve replacement. CONCLUSION: DA-TAVR provides a safe and viable alternate access approach for patients with inadequate ileo-femoral access. The clinical outcomes were acceptable in this very high-risk group of patients. PMID- 26897811 TI - Ivabradine in Severe Aortic Stenosis with Poor Left Ventricular Ejection Fraction. AB - Patients with severe aortic stenosis (AS) and left ventricular systolic dysfunction pose a significant challenge to the managing physician. Conventional pharmacological therapy for systolic heart failure has not been proven beneficial in this setting. Ivabradine, a selective current inhibitor, decreases the spontaneous firing rate of sinoatrial nodal cells, thereby reducing the heart rate, and has been shown to reduce a composite end-point of heart failure hospitalization and mortality in patients with impaired left ventricular function. Herein are reported details of the hemodynamic effects and clinical outcome of ivabradine treatment in an 86-year-old man with severe AS and severe left ventricular systolic function. PMID- 26897812 TI - Aortic Annulus Rupture During TAVI: A Therapeutic Dilemma in the Inoperable Patient. AB - Aortic annulus rupture is a rare complication of transcatheter aortic valve implantation (TAVI), related to relative valve oversizing or eccentric calcification. A case is reported of periprocedural cardiac tamponade caused by aortic annulus rupture. Optimal management of periprocedural aortic annulus rupture and pseudoaneurysm formation in patients considered too frail for surgery should be discussed in a multidisciplinary setting. PMID- 26897813 TI - The Impact of Transcatheter Aortic Valve Implantation on Mitral Regurgitation Regression in High-Risk Patients with Aortic Stenosis. AB - BACKGROUND AND AIM OF THE STUDY: In patients with aortic stenosis, mitral regurgitation (MR) is a common finding. Little is known regarding outcomes of MR in patients undergoing transcatheter aortic valve implantation (TAVI). The study aim was to characterize the short- and mid-term impact of the TAVI procedure on MR grade. METHODS: A total of 261 patients (59% females; mean age 82.1 +/- 6.9 years) undergoing TAVI was assessed for rates of significant MR and the severity of MR at baseline, and at one month and six months after the procedure. RESULTS: In patients with moderate MR or above at baseline (n = 26, 10% of the cohort), there was a mean reduction in grade of 1.5 +/- 1.1 and 1.8 +/- 1.4 after one and six months, respectively (p < 0.01). Reduction in MR grade (1+) at six months was identified in 54.1% (40/74) of patients with mild-moderate MR or greater, and in 88.5% (23/26) of those with moderate MR or above, and was associated with an improved NYHA functional class (correlation coefficient r = -0.294, p < 0.001). Multivariate analysis identified low pulmonary pressure and tricuspid regurgitation as independent predictors of improvements in MR. CONCLUSION: Among the present cohort of patients undergoing TAVI, those with MR at baseline showed an improvement in the severity of their MR. Patients with moderate MR regurgitation or above demonstrated the greatest improvement. PMID- 26897814 TI - Evaluation of the Role of Oxidative Stress in Degenerative Aortic Stenosis. AB - BACKGROUND AND AIM OF THE STUDY: Calcific and degenerative aortic diseases (CDADs) are a group of disorders that mostly affect the elderly population and may progress and warrant aortic valve replacement. It is believed that oxidative stress plays a role in the progression of the diseases. Several markers of oxidative stress were evaluated in a small cohort of patients with CDADs, and a control group with similar characteristics. METHODS: Thirty patients with aortic stenosis (AS) and 30 healthy subjects were included in the study. The activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) in both groups were studied as markers of oxidative stress. All patients and control subjects were evaluated echocardiographically for CDAD, and enzyme levels monitored biochemically. RESULTS: The risk factors were similar in both groups, but levels of low-density lipoprotein (LDL) were higher in the CDAD group compared to controls (123.6 +/- 37.0 mg/dl versus 99.3 +/- 38.0 mg/dl, p < 0.01). The GSH-Px activity was significantly higher in the CDAD group than in controls (0.19 +/- 0.03 IU/ml versus 0.16 +/- 0.03 IU/ml, p < 0.01). A GSH-Px level > 0.18 IU/ml was found to be an indicator of CDAD, with a sensitivity of 70% and specificity of 73.3% on ROC analysis [AUC = 0.721, p < 0.05, 95% CI: 0.685 +/- 0.773]. SOD and CAT activities were similar in both groups (p > 0.05). CONCLUSION: The study results showed that the activity of GSH-Px, a marker of oxidative stress, is increased in patients with degenerative AS. The increase in GSH-Px activity may be a protective response to remove reactive oxygen derivatives (RODs) from the body. PMID- 26897815 TI - C4b-Binding Protein Deposition is Induced in Diseased Aortic Heart Valves, Coinciding with C3d. AB - BACKGROUND AND AIM OF THE STUDY: It has been found recently that activated complement is more widespread in diseased aortic valves compared to the endogenous complement inhibitors C1-inhibitor and clusterin. Previously, another endogenous inhibitor of complement, C4b-binding protein (C4BP) has been described in atherosclerotic diseased coronary arteries. The study aim was to analyze C4BP levels in diseased aortic valves. METHODS: Aortic valve tissue was derived from surgical procedures and classified as 'degenerative', 'atherosclerotic' or 'atherosclerotic with bacterial infection'. Valves were stained with specific antibodies against C4BP, C3d and caspase-3. Areas of positivity were then quantified using computer- assisted morphometry. RESULTS: In atherosclerotic valves, the areas of C4BP and C3d positivity (38.8 +/- 0.4% versus 32.7 +/- 1.0%, respectively) were significantly higher compared to the degenerative and control groups. In atherosclerotic valves with bacterial infection, the area of positivity for C4BP was even further increased compared to atherosclerotic valves (65.1 +/- 1.2%; 70.1 +/- 1.9% for C3d). The areas of C4BP and C3d positivity were not significantly different in all groups. Caspase-3 was only present in <10% of endothelial cells in the atherosclerotic valves without bacterial infection and in neutrophilic granulocytes in atherosclerotic valves, with and without bacterial infection. CONCLUSION: It has been shown for the first time that C4BP is deposited in the diseased aortic valve, coinciding with C3d. The area of C4BP positivity was more extensive compared to the areas of other endogenous complement inhibitors (C1-inhibitor and clusterin). PMID- 26897816 TI - Myocardial and Cardiocirculatory Reserve in Asymptomatic Aortic Stenosis and Preserved Ejection Fraction. AB - BACKGROUND AND AIM OF THE STUDY: Managing patients with asymptomatic severe aortic stenosis (AS) remains a major challenge. Myocardial as well as cardiocirculatory reserve have been hypothesized to predict outcome in patients with asymptomatic AS. METHODS: A total of 48 patients (indexed aortic valve area 0.39 +/- 0.12 cm2/m2; ejection fraction (EF) 67 +/- 7%) underwent spiroergometry and dobutamine stress echocardiography. Death or valve surgery served as a combined endpoint for follow up. RESULTS: Thirty-seven patients reached the endpoint after a mean of 756 days (range: 100-2146 days). Age- and gender corrected univariate Cox proportional analysis revealed the presence of mild obstructive lung disease, stroke work loss (SWL), end-systolic diameter index, and E/Flow propagation velocity as the best predictive clinical, valvular, cardiostructural, and left ventricular filling pressure parameters, respectively. After inclusion of these parameters into a baseline multivariable Cox proportional hazard model, SWL (HR 1.21 per rise of 1 unit, CI 1.08-1.35, p = 0.0005) and female gender (HR 3.37, CI 1.50-7.59, p = 0.0044) were independently predictive. Similarly, the best-performing myocardial parameter, EF after dobutamine, was independently predictive (HR 0.75 per 5 units, CI 0.57-0.99, p = 0.035) after inclusion. The best-performing exercise capacity parameter, Watt(max), was of borderline significance (HR 0.93 per 5 units, CI 0.86-1.00, p = 0.0505). For each parameter, cut-off values were determined by time-dependent receiver-operator characteristics. The Kaplan-Meier curves of the patients above versus below the cut-offs differed significantly for SWL (p = 0.001), Wattm (p = 0.001), and gender (p = 0.013). CONCLUSION: Besides SWL and female gender, the EF after dobutamine as well as highest exercise stress intensity reached are helpful in determining the prognosis of asymptomatic patients with moderate-severe AS. PMID- 26897817 TI - Sigmoid Septum and Balloon-Expandable Transcatheter Aortic Valve Replacement: A Cautionary Tale. AB - Transcatheter aortic valve replacement (TAVR) continues to garner considerable attention, especially as the commercial use of the procedure grows. Herein is highlighted an under-reported, underappreciated challenge in TAVR--that of a sigmoid septum. The two cases reported constitute the first discussion in the contemporary literature of this unique geometry in the setting of TAVR. Specifically, the report addresses how such a bulging septum may preclude safe TAVR with a balloon- expandable prosthesis, and also reinforces the importance of thoroughly evaluating all aspects of the subvalvular anatomy prior to valve deployment. PMID- 26897818 TI - The So-Called 'Eclipsed' Mitral Regurgitation. AB - An 89-year-old female was referred to the authors' institution for repeating pulmonary edema. Recent transthoracic echocardiography (TTE) showed only a mild mitral regurgitation (MR), but a transient severe reversible functional MR was observed during an episode of respiratory distress. TTE demonstrated the functional nature of the regurgitation with a transient tenting of the mitral leaflets, resulting in a total absence of coaptation. PMID- 26897819 TI - Early and Late Outcomes After Minimally Invasive Mitral Valve Repair Surgery. AB - BACKGROUND AND AIM OF THE STUDY: The practice of thoracoscopic assisted minimally invasive mitral valve repair surgery is less common in the United Kingdom than in Europe or the USA. The main reasons for this are concerns around increased operative risk, feasibility and durability of valve repair. The study aim was to report the early and late outcomes of minimally invasive mitral valve repair surgery at a single U.K. center. METHODS: Patients undergoing isolated minimally invasive mitral valve repair between 2003 and 2013 were reviewed retrospectively. Data were obtained from a prospectively maintained institutional database, a comprehensive review of individual case notes, echocardiograms, intensive care charts, clinic letters, discharge summaries, and the authors' follow up database (based on data supplied by the UK Office for National Statistics). RESULTS: A total of 190 patients (mean age 61 years; mean EuroSCORE 3.9) underwent the procedure. The mean cardiopulmonary bypass and aortic cross-clamp times were 153 and 108 min, respectively. Rates of major postoperative complications were: reoperation for bleeding 3.7%, stroke 1.6%, intra-aortic balloon pump 2.1%, and venovenous hemofiltration 2.6%. The median intensive care stay was one day, and the median hospital stay five days (21.8% of patients were discharged by day 3). The 30-day mortality was 1.1% (n = 2). Echocardiography performed at discharge or six weeks postoperatively showed less than mild mitral regurgitation (MR) in 91.3%. The median duration of follow up was 57 months. During the entire follow up period, four patients (2.1%) underwent repeat surgery for recurrent MR (between 15 months and five years). Of 188 patients discharged from hospital, nine (4.8%) died during follow up: median 5.3 years (range 1.3- 10.7 years) post surgery. CONCLUSION: These data are the first from the U.K. demonstrating early and late outcomes after thoracoscopic assisted minimally invasive mitral valve repair surgery. The data establish the safety and efficacy of the technique and, importantly, lend further support towards a prospective randomized comparison of minimally invasive versus conventional mitral valve repair surgery. PMID- 26897820 TI - Does the Homograft for RVOT Reconstruction in Ross: Patients Fare Better than for Non-Ross Patients? A Single-Center Experience. AB - BACKGROUND AND AIM OF THE STUDY: In patients undergoing the Ross procedure, the right ventricular outflow tract (RVOT) conduit is inserted in an orthotopic position rather than in the more heterotopic position used in the repair of complex congenital RVOT obstruction. The study aim was to compare the authors' institutional mid-term experience of large-sized homografts (>19 mm) in patients with Ross and non-Ross RVOT reconstructions. METHODS: The outcome was reviewed of all homografts implanted for Ross (n = 72) or non-Ross (n = 64) RVOT reconstruction at a single center between 1993 and 2012. Echocardiographic data were reviewed to evaluate valve performance. Homograft dysfunction was defined as RVOT obstruction with peak echo-Doppler gradient >40 mmHg and/or grade >III/IV conduit valve regurgitation. Homograft failure was defined as the need for conduit replacement or catheter or surgical reintervention. RESULTS: The age, body weight, conduit diameter and previous surgery were significantly higher in patients with Ross compared to the non-Ross group (p = 0.002, 0.003 and <0.001, respectively). The mean follow up duration was similar in both groups. There were 35 re-interventions (Ross, n = 17; non-Ross, n = 18). The data acquired showed actuarial survival, freedom from conduit dysfunction and conduit failure to be similar in both cohorts. Freedom from any type of reoperation was worse for the Ross group (58%) than for the non-Ross group (72%) (p = 0.05). CONCLUSION: During the first 15 years after Ross or non-Ross pulmonary homograft implantation, the survival rate, freedom from failure and dysfunction, and RVOT gradient were statistically similar. Freedom from any type of reoperation was significantly higher in the non-Ross group, however. PMID- 26897821 TI - Feasibility of Valve-in-Valve Procedure for Degenerated St. Jude Medical Trifecta Bioprosthesis. AB - The valve-in-valve (ViV) procedure is an option for patients with symptomatic structural degeneration of a bioprosthesis and excessive reoperative risk. The risk of coronary obstruction appears to be increased if ViV is performed for certain pericardial prostheses in which the leaflets are mounted outside the stent posts. Herein is described a successful ViV for a degenerated Trifecta aortic bioprosthesis, and the technical considerations for performing a ViV procedure within such types of prosthesis are considered. Emphasis is placed on the importance of preoperative investigations (computed tomography scan-based measurements of coronary ostial height and of sinus of Valsalva diameters), and on the precise deployment of the valve (transapical approach with transesophageal echocardiography control) to minimize the risk of major complications. The presence of a failing Trifecta bioprosthesis should not be considered an absolute contraindication to ViV on the basis of the risk of coronary obstruction. PMID- 26897822 TI - A Matched-Paired Comparative Analysis of the Hemodynamics of the Trifecta and Perimount Aortic Bioprostheses. AB - BACKGROUND AND AIM OF THE STUDY: Current cohort studies comparing the Trifecta valve to alternative pericardial bioprostheses are limited by selection bias. The study aim was to determine if hemodynamics are improved after the aortic valve implantation of a Trifecta valve as compared to a standard pericardial valve, when evaluated using strict paired matching for specific key relevant confounders. METHODS: Valve hemodynamics were compared in patients undergoing implantation with a Trifecta or Perimount valve matched for left ventricular outflow tract (LVOT) diameter, gender, age, body size, and days since surgery, using a 1:1 matched-paired cohort analysis (n = 20 per group). RESULTS: Patients receiving a Trifecta valve had a larger increase in indexed stroke volume (SVi) relative to baseline compared to the Perimount patients (p = 0.013), in whom SVi was decreased. The mean transvalvular pressure gradient was lower in Trifecta patients despite the larger SVi (p = 0.02). The effective orifice area (EOA) and indexed EOA (EOAi) were significantly larger in Trifecta patients compared to Perimount patients (2.04 +/- 0.46 versus 1.77 +/- 0.45 cm2, p = 0.049; 1.10 +/- 0.22 versus 0.95 +/- 0.06 cm2/m2, p = 0.027, respectively), and there was a greater increase in EOA and EOAi from baseline (p = 0.010 for both). Severe prosthesis-patient mismatch (PPM) (EOAi < or = 0.65 cm2/m2) was seen in two (10%) of the Perimount cases, but in none of the patients with the Trifecta valve (p = 0.072). CONCLUSION: Trifecta valve implantation is associated with a significant improvement in EOA and a decreased incidence of PPM as compared to the Perimount valve. The superior hemodynamic outcomes observed support consideration of this valve for aortic valve replacement, particularly in patients with a small LVOT at risk for PPM. PMID- 26897823 TI - The Role of Interleukin-13 in Patients with Rheumatic Valvular Fibrosis: A Clinical and Histological Study. AB - BACKGROUND AND AIM OF THE STUDY: Interleukin (IL)-13 is a major inducer of fibrosis in many chronic infectious diseases, yet few studies have reported its role in valvular fibrosis in patients with rheumatic heart disease (RHD). The study aim was to investigate the role of IL-13 in mitral valvular fibrosis in patients with RHD. METHODS: Peripheral blood samples were collected from surgical patients with RHD (n = 18) and from healthy controls (n = 9). Serum levels of IL 13 and interferon (IFN)-gamma were analyzed using ELISA. Rheumatic mitral valves removed from surgical patients with RHD, and normal mitral valves, were obtained at autopsy. The expression and distribution of collagen I, collagen III, and IL 13Ralpha1 were examined by immunohistochemical staining, the degree of which was measured using computed imaging analysis. RESULTS: Higher IL-13 levels were observed in RHD patients (15.16 +/- 9.62 pg/ml; p < 0.05) than in healthy controls (7.78 +/- 3.87 pg/ml). RHD patients had high levels of IFN-gamma (9.95 +/- 0.77 pg/ml; p <0.05) compared to healthy controls (5.95 +/- 0.69 pg/ml). Immunohistochemistry showed that, compared to normal valves, rheumatic mitral valves expressed high levels of collagen I (0.01931 +/- 0.00159 versus 0.01183 +/ 0.00207; p < 0.05), collagen III (0.00726 +/- 0.00078 versus 0.00342 +/- 0.00124; p <0.05), and IL-13Rcxl (0.00454 +/- 0.00086 versus 0.00017 +/- 0.00008; p <0.01). Collagens I and III were each expressed in heart interstitial cells, while IL-13Ralpha1 was expressed in the endothelial cells and smooth muscle cells of the blood vessels, and in interstitial cells. CONCLUSION: Patients with RHD showed increased serum levels of IL-13 compared to healthy controls. IFN-gamma levels were clearly different among RHD patients and healthy controls. The expression of collagens I and III and IL-13Ralpha1 was higher in rheumatic mitral valves compared to normal mitral valves. IL-13 may induce mitral valvular fibrosis in RHD. PMID- 26897824 TI - Incremenal Value of Cardiac Magnetic Resonance for Assessing Pulmonic Valve Regurgitation. AB - BACKGROUND AND AIM OF THE STUDY: Cardiac magnetic resonance (CMR) is the 'gold standard' for quantifying pulmonic regurgitation (PR) in adults with congenital heart disease, but remains costly and is less readily available than echocardiography. Qualitative echocardiographic assessment of PR is challenging, and guiding criteria are limited. It is unknown if echocardiography is sufficient to screen for significant PR. The study aim was to determine whether cardiac MRI provides additional benefit in the assessment of PR in adults with congenital heart disease. METHODS: Patients with repaired tetralogy of Fallot or congenital pulmonic stenosis after valvotomy undergoing transthoracic echocardiography and CMR with no interval intervention were identified from a prospective registry. Patients with greater than mild pulmonic stenosis, residual ventricular septal defect or poor echocardiographic windows were excluded. Whole-cohort and subgroup (tetralogy of Fallot versus pulmonic stenosis) analyses for inter-modality agreement were performed. RESULTS: A total of 48 patients (24 men, 24 women; mean age 43 +/- 12 years) was included in the analysis. The unweighted kappa value for the two modalities was 0.30, suggesting 'fair' agreement, though only 52% had matching PR assessments. The indexed right ventricular end-systolic volume (RVESVi) correlated closely with cardiac MRI-monitored PR (p = 0.011 by analysis of variance), but not with that monitored with echocardiography (p = 0.081). Subgroup analysis demonstrated less inter-modality agreement in the tetralogy of Fallot population (kappa 0.25) than in the pulmonic stenosis population (kappa 0.35). CONCLUSION: CMR measurement of PR correlates closely with the RVESVi, and appears superior to echocardiography when assessing patients at risk for PR. The study results suggest a vital role for CMR whenever significant PR is suspected in the adult congenital heart disease population. PMID- 26897825 TI - Prophylactic Tricuspid Annuloplasty in Patients Undergoing Double Valve Revlacement. AB - BACKGROUND AND AIM OF THE STUDY: The study aim was to evaluate the effect of prophylactic tricuspid annuloplasty (TAP) on late tricuspid regurgitation (TR) after double valve (aortic and mitral) replacement (DVR). METHODS: Among 239 patients undergoing DVR at the authors' institution between 1994 and 2009, a total of 93 patients who had a less than moderate degree of preoperative TR was analyzed. Concomitant TAP was performed in 55 patients (TAP group). The mean follow up duration was 7.3 +/- 4.1 years (maximum 15.9 years). Serial echocardiographic data at one, three, five and more than seven years were analyzed. RESULTS: There was no early mortality, but eight late cardiac-related mortalities occurred (8.6%). In the aortic position, the transprosthetic mean pressure gradient (TMPG) was increased during follow up (13.5 +/- 5.3 mmHg versus 16.4 +/- 10.2 mmHg, p = 0.006). However, the mitral TMPG did not change significantly (3.7 +/- 1.4 mmHg versus 3.8 +/- 1.6 mmHg, p = 0.677). Freedom from valve-related events at 10 years was higher in the TAP group than in the non-TAP group (85.2 +/- 5.9% versus 63.3 +/- 0.9%; p = 0.05). Freedom from more than moderate TR at 10 years was also higher in the TAP group (93.6 +/- 4.7% versus 66.3 +/- 10.3%; p = 0.03). The transmitral pressure gradient was associated with valve-related events (p = 0.025; HR, 1.367). An absence of TAP was predictive of late TR (p = 0.020; HR, 4.4). CONCLUSION: The study results suggested that TAP can be considered in patients who require DVR, even if the TR grade is less than moderate, in order to prevent the late occurrence of TR. PMID- 26897826 TI - Aortic Root Enlargement with Ascending-to-Descending Aortic Bypass in Repair of Coarctation. AB - Ascending-to-descending aortic bypass is a valuable technique for addressing coarctation of the aorta when additional cardiac procedures are indicated in adults. Among these, aortic valve replacement is one of the most commonly performed concomitant procedures, and there are instances in which aortic root enlargement is required. Herein, a novel technique is described for performing simultaneous ascending-to-descending aortic bypass in conjunction with aortic root enlargement which incorporates the bypass graft as part of the aortic root enlargement. PMID- 26897827 TI - Conventional Aortic Valve Replacement after Displacement of a Percutaneously Implanted Aortic Prosthesis: Case Report. AB - A case is described of aortic stenosis that was initially treated with transcatheter aortic valve implantation (TAVI) due to a high-risk profile. Following dysfunction of the TAVI prosthesis, conventional aortic valve replacement (AVR) was successfully performed; the subsequent postoperative course was uneventful. In conclusion, the target population for TAVI must be more accurately specified, with further research helping to define whether AVR or TAVI is the best treatment option for 'intermediate-risk' patients. PMID- 26897828 TI - Double-Orifice Mitral Valve in an Eight-Year-Old Boy. AB - The case is described of an eight-year-old boy who required an operation for moderate mitral regurgitation due to a double-orifice mitral valve (DOMV). The DOMV, which was clearly demonstrated by transthoracic echocardiography, had a central fibrous bridge. Mitral valve repair using a 5/0 Prolene suture placed at the level of the superior commissure of each hole to stabilize the valve, and ring annuloplasty with Edwards Physio ring, was successfully performed. Intraoperative real-time transesophageal echocardiography showed the repaired DOMV to be without regurgitation or stenosis. PMID- 26897829 TI - Surgery for Congenital Tricuspid Valve Cleft: Tricuspid Valve Repair with Neochordae and Annuloplasty. AB - BACKGROUND AND AIM OF THE STUDY: Congenital abnormalities of the tricuspid valve (TV), including dysplasia, straddling, and those associated with other congenital heart disease, are rare causes of tricuspid regurgitation (TR). In congenital TV anomalies there can be varying levels of abnormalities of leaflet and subvalvular structures. Herein is reported a case of TV cleft with absent chordae, and a technique of TV repair. METHODS: A 14-year-old boy was found to have severe TR due to dysplasia of the anterior TV leaflet. Intraoperatively he was noted to have dysplasia of the TV with a cleft in the anterior leaflet of the TV and an absence of chordae supporting the anterior two-thirds of the anterior leaflet. The anterior papillary muscle was hypoplastic, with chordae to the posterior leaflet and small chordae partly to the anterior leaflet. The cleft was repaired and a neochordae placed onto the anterior leaflet with attachment to the papillary muscle, followed by an annuloplasty. RESULTS: Intraoperative and postoperative echocardiographic assessment showed good mobility of the anterior tricuspid leaflet at six months and two-year follow up. CONCLUSION: Chordal replacement is a useful technique for repairing congenital dysplastic TV with absent chordae. The same technique for mitral valve repair with neochordae can be applied to chordal anomalies of the TV, with excellent outcome. PMID- 26897830 TI - Shifting a Paradigm of Cardiac Surgery: From Minimally Invasive to Micro Invasive. AB - The development of new techniques for the treatment of almost all structural heart pathologies that do not require cardiopulmonary bypass and aortic cross clamping, such as transcatheter aortic valve replacement and transapical mitral chordae implantation, define a new age of our specialty: the micro-invasive (microICS) cardiac surgery era. PMID- 26897831 TI - Minimally Invasive Aortic Valve Replacement: Cost-Benefit Analysis of Ministernotomy Versus Minithoracotomy Approach. AB - BACKGROUND AND AIM OF THE STUDY: Minimally invasive aortic valve replacement via ministernotomy (ministernotomy-AVR) or minithoracotomy (minithoracotomy-AVR) is gaining popularity. To date, a direct comparison of ministernotomy-AVR versus minithoracotomy-AVR is lacking. The study aim was to compare these two procedures from a cost-benefit perspective. METHODS: Eight reports from the United States were selected from amongst 33,494 literature citations based on sample size and data completeness. Perioperative variables were collected for each surgical approach. Fixed and variable costs were estimated as cost per case in excess of full sternotomy AVR procedures. RESULTS: Ministernotomy-AVR patients were of a significantly lower mean age (59.8 years versus 67.9 years), ejection fraction (50.4-51.6% versus 56.1-57.8%), shorter cardiopulmonary bypass time (97.2 min versus 125.6 min) and cross-clamp time (69.9 min versus 87.9 min), a lower rate of blood transfusion (25.9% versus 64.4%), and a shorter length of hospital stay (5.7 versus 6.2 days). There were no significant inter-group differences in 30 day mortality, conversion to sternotomy, neurologic events, arrhythmia, wound infection, or postoperative bleeding. Assuming a volume of 50 cases per year, the added operative cost per case for a minithoracotomy-AVR was US$ 4,254 compared to US$ 290 for a ministernotomy-AVR. The added costs per case, assuming 200 cases per year, were US$ 4,209 and US$ 290, respectively. A minithoracotomy-AVR program performing 50 cases per year adds US$ 1,063,665 of operative costs over five years, compared to US$ 72,500 for a ministernotomy-AVR program. CONCLUSION: The present analysis suggested that the clinical benefits of ministernotomy-AVR are comparable or better than those of minithoracotomy-AVR, and at lower costs. Healthcare delivery organizations should consider the results of cost-benefit examinations when developing surgical valve replacement programs. PMID- 26897832 TI - Quality of Life Shift after Aortic Valve Replacement in the Era of TAVI: Single Center Class Comparison Study Between Different Procedural Techniques. AB - BACKGROUND AND AIM OF THE STUDY: The health-related quality of life (QOL) is one of the most important outcome indicators for elderly people undergoing aortic valve interventions, and should be assessed across different interventions, including emerging percutaneous techniques. The study aim was to assess the change in QOL after different procedures for aortic valve replacement (AVR). METHODS: QOL was assessed using the Short Form-36 questionnaire (SF-36) for 59 patients after conventional AVR; of these patients, 28 had AVR via a J sternotomy, a transapical approach was used in 20 patients, and a transfemoral approach in 34. RESULTS: The early mortality during hospitalization was not significantly different among all four groups. The inverse probability weighted propensity scores adjusted Kaplan-Meier curve revealed that the transapical group had the lowest survival rate. The treatment effect analysis was most prominent in the transfemoral transcatheter aortic valve implantation (TAVI) group across all domains for QOL. The multivariate hierarchical linear mixed final fitted model shows that the transapical TAVI procedure and NYHA class (III-IV) had a significant negative effect on the physical domain and overall QOL score. CONCLUSION: Changes in QOL after interventions on the aortic valve were determined by the patient's preoperative status and the surgical intervention. The transcatheter intervention, even in 'sicker' patients, provided a gain in QOL comparable with that after an open-heart procedure. Transfemoral TAVI was shown to have advantages over transapical TAVI in terms of QOL improvement at three months and six months, and should be considered the first choice for patients in the high-risk surgical group. PMID- 26897833 TI - Novel Method of Assessing Ascending Aorta with a Stenotic Bicuspid Aortic Valve. AB - BACKGROUND AND AIM OF THE STUDY: Patients with bicuspid aortic valve (BAV) have an increased risk of serious aortic complications such as aortic dissection, rupture and dilatation of the ascending aorta. Previous findings have suggested that ascending aortic dilatation with a BAV has a typical asymmetric configuration at the right-anterior aspect of the aorta. The study aim was to quantify asymmetric configurations of the aorta using a three-dimensional (3D) reconstruction tool. METHODS: A retrospective review was conducted of 52 patients (27 males, 25 females; mean age 69 ? 9 years) with aortic stenosis who presented with ascending aortic dilatation defined as an aortic diameter >35 mm. Of these patients, 24 (46%) had a BAV and 28 (54%) had a tricuspid aortic valve (TAV). A patient-specific 3D thoracic aortic model was reconstructed from computed tomography (CT) data. Three-dimensional centerlines were automatically calculated. The size of the ascending aorta was determined by calculating the cross-sectional area (in mm2) of the vertical section against the centerline. The symmetry of the dilated aorta was evaluated as the ellipticity of the maximum vertical section of the ascending aorta. The size and symmetry of the ascending aorta, and background factors including pressure gradient, aortic valve area, degree of regurgitation, ejection fraction and cardiovascular risk factors, were compared between the BAV and TAV groups. RESULTS: Only age differed significantly between the groups (p = 0.003). The size and ellipticity of the ascending aorta and the maximum cross-sectional area of the aortic arch were significantly greater in the BAV group (p = 0 .001 and p = 0.004, respectively). CONCLUSION: The ascending aorta assessed using Mimics 3D reconstruction software was frequently asymmetrically dilated in stenotic BAV, and the expansion progressed to the aortic arch. It is believed that calculating the ellipticity of the vertical section against the centerline offers an innovative means of quantifying aortic symmetry in three dimensions. PMID- 26897834 TI - Intra- and Inter-Observer Reproducibility of Transcatheter Aortic Valve Replacement Planning Measurements by Multidetector Computed Tomography. AB - BACKGROUND AND AIM OF THE STUDY: Multidetector computed tomography (MDCT) is widely used for transcatheter aortic valve replacement (TAVR) planning, and its use predicts and prevents complications. To date, the reproducibility of aortoiliofemoral measurements and prediction of fluoroscopic angles for TAVR deployment remain inadequately studied. METHODS: Twenty-five consecutive patients (six males, 19 females; mean age 81.1 years) undergoing pre-procedural evaluation for TAVR were studied for 74 separate variables by MDCT. Two experienced readers made repeated measurements of the diameter and area of the aortic annulus, the aortic root at the level of the sinuses of Valsalva, sinotubular junction, and ascending aorta, and the diameters of peripheral vessels at the level of the distal abdominal aorta, and the iliofemoral arteries. A fluoroscopic angle prediction was obtained for left anterior oblique (LAO) 0 degrees, 20 degrees and 30 degrees projections. Pearson's correlation coefficient (r) was obtained, and intra-class correlation coefficients and Bland-Altman plots were generated to examine agreements, respectively. RESULTS: The mean aortic valve area was 0.7 cm2. Each measurement generally showed good intra- and inter-observer reproducibility. The mean difference between readers was -0.3 mm for mean annular diameter and 3.6 mm2 for annular area. The area- derived diameter showed better reproducibility than the mean diameter (ICC 0.87, 0.84). However, the right coronary artery height showed poor inter-observer agreement (ICC 0.48). Angle predictions for 0 degrees, 20 degrees and 30 degrees-LAO were reproducible within and between readers (ICC 0.68-0.96 and 0.75-0.85). Qualitative assessments were also reliable between readers. CONCLUSION: Inter- and intra-observer measurements of the pre-TAVR planning parameters are reliable, with generally a high degree of agreement. PMID- 26897835 TI - Fate of Normally Functioning Bicuspid Aortic Valve in Patients Undergoing Ascending Aorta Surgery. AB - BACKGROUND AND AIM OF THE STUDY: Bicuspid aortic valve (BAV), though normally functioning, is frequently associated with dilatation of the aortic root and ascending aorta. Optimal surgical treatment remains controversial. The study aim was to evaluate the fate of the normally functioning spared BAV at long-term follow up. METHODS: Forty patients (26 males, 14 females; mean age 59 +/- 11 years; range: 38-81 years) who underwent aortic surgery for proximal aortic disease between 1996 and 2011, with spared BAV at surgery, were included in the study. The main indication for surgery was ascending aorta aneurysm. Of the patients, 37 had ascending aorta replacement and three underwent a semi-Yacoub procedure. Adjunctive subcommissural annuloplasty was performed in 12 cases. The clinical and echocardiographic follow up (median 62 months; range: 7-175 months) was 100% complete. RESULTS: In-hospital survival was 100%. Pre-discharge echocardiography showed no cases of significant aortic regurgitation (grade > or = 3+) or stenosis. The probability of survival at five and 10 years was 93 +/- 7% and 79 +/- 10%, respectively. Two surviving patients (5%) required reoperation for the development of aortic insufficiency. Freedom from aortic valve replacement was 100% and 90 +/- 10% at five and 10 years, respectively, and freedom from thromboembolic or bleeding events was 100% and 90 +/- 10% at five and 10 years, respectively. No cases of endocarditis were reported. The composite event-free survival at five and eight years was 85 +/- 6% and 69 +/- 11%, respectively. There were no cases of root enlargement during the follow up period. CONCLUSION: A spared BAV offers a good time-span of functional integrity. The conservative approach seems to be a valid strategy, with a low risk of reintervention and cardiovascular events during long term follow up, in selected patients. PMID- 26897836 TI - Prognostic Implication of Three-Dimensional Mitral Valve Tenting Geometry in Dilated Cardiomyopathy. AB - BACKGROUND AND AIM OF THE STUDY: Functional mitral regurgitation (FMR) is a clinically important complication of left ventricular (LV) dysfunction, occurring as a result of geometric deformity in the mitral valve (MV) complex. The study aim was to determine whether tenting parameters derived from real-time three dimensional echocardiography (RT3DE) can predict the long-term prognosis for patients with dilated cardiomyopathy (DCM). METHODS: Mitral valve tenting morphology, LV volume and function, and papillary muscle positions were monitored using transthoracic RT3DE in 75 subjects (66 with DCM, nine controls). The maximum tenting sites of the leaflet (maxTS) were also mapped from the reconstructed 3D images, to determine if the 3D tenting parameters correlated to long-term outcome. RESULTS: Follow up information was collected from 62 patients with DCM over a mean period of 42 +/- 31 months. Cardiovascular events occurred in 30 patients (48%), including 13 cardiac deaths (21%). The patients were allocated to an Event group (n = 30) or a Non-event group (n = 32). The LV volumes were significantly larger and LV ejection fraction was lower in the Event group compared to the Non-event group. The 3D tenting volumes were significantly larger in the Event group than the Non- event group (p = 0.05). The maxTS were positioned mostly in the middle portion of the anterior mitral leaflet in the Non event group (maxTS-mid AML), but in the Event group they were mostly found in the MV coaptation region of the leaflet (maxTS-coapt) (p <0.001). Patients with maxTS coapt had a worse prognosis compared to those with maxTS-mid AML. On multivariate Cox regression analysis, maxTS was the strongest predictor of event-free survival. CONCLUSION: The 3D tenting pattern, assessed with RT3DE, would be an important clinical parameter in predicting long-term prognosis in patients with DCM. PMID- 26897837 TI - Cusp-Level Chordal Shortening for Non-Rheumatic Mitral Anterior Leaflet Prolapse in a Patient with Persistent Atrial Fibrillation. AB - The case is reported of mitral valve repair with cusp-level chordal shortening for non-rheumatic mitral anterior leaflet prolapse. The simple and easily reproducible cusp-level shortening procedure consists of plication of the redundant chorda underneath the leaflet. Provided the chorda is thick enough, this procedure is more likely to be applied to regional mitral anterior prolapse due to elongation of the chorda, even in patients with non-rheumatic heart disease. The present patient underwent perioperative adaptive servo-ventilation (ASV) therapy. ASV might help to prevent atrial fibrillation recurrence after the Maze procedure by reducing sympathetic overactivity, contributing to the durability and outcome of mitral valve repair with cusp-level chordal shortening. PMID- 26897838 TI - Managing Ventricular Septal Defect with Associated Aortic Regurgitation: Two Decades of Experience. AB - BACKGROUND AND AIM OF THE STUDY: Ventricular septal defect (VSD) with aortic regurgitation (AR) is a well-known association. However, there is still no agreement about its management, particularly regarding the technical details of its operative treatment. The study aim was to describe all components of the syndrome and to evaluate the various techniques used with regards to its anatomical and functional features. METHODS: A total of 31 patients (mean age 7.4 years; range: 1.0-14.3 years) who underwent repair of VSD and AR between 1990 and 2013 was reviewed. The VSD was perimembranous in 22 patients, and subarterial in nine. Trusler's valvuloplasty technique was used in 15 patients, Yacoub's technique in seven, and Carpentier's technique (triangular resection) in four. Two patients underwent aortic valve replacement (AVR), and three patients with no significant aortic valve lesions underwent a simple patch repair of the VSD. RESULTS: The aortic valvuloplasty results were generally good, with an initial aortic valvuloplasty avoiding AVR. During the immediate postoperative period, valvuloplasty failure occurred in three patients, regardless of the technique used, and all three patients were reoperated on. The mean duration of follow up was 8.5 years (range: 3.2-20.6 years). The initial result was maintained in all patients, except for four who underwent late AVR. CONCLUSION: The study findings contributed to an analysis of VSD and AR, and helped to clarify the best surgical strategy. The results obtained suggest that adequacy of the initial repair is the most important determinant of subsequent evolution. PMID- 26897839 TI - A Comprehensive Fluid Dynamic and Geometric Study for an "In-Vitro" Comparison of Four Surgically Implanted Pericardial Stented Valves. AB - BACKGROUND AND AIM OF THE STUDY: Many variables may affect the fluid dynamic of an implanted bioprosthesis. In-vitro studies have provided accurate data such that, when different prostheses are implanted in the same true aortic root, it should be possible to make a fair comparison. The study aim was to evaluate the fluid dynamic and geometric characteristics of the four most widely used stented pericardial bioprostheses. METHODS: Four types of pericardial prosthesis (Magna Ease 21, Trifecta 21, Soprano-Armonia 20, and Mitroflow 23) that fitted eight aortic roots with a native annulus diameter of 2.1 cm were implanted and tested in a mock loop. RESULTS: Energy loss and mean gradients were increased with stroke volume (SV) in all valves tested. The effective orifice area values were fairly stable across the SV intervals (p = 0.57). All hemodynamic-related indices displayed mutually consistent behaviors, with Trifecta showing the lowest hindrance to flow. Both geometric orifice area (GOA) and edge geometric orifice area (eGOA) were increased significantly as the SV increased; the Trifecta valve showed the largest eGOA value, while the Trifecta and Mitroflow provided the largest GOAs. For the Trifecta and Soprano-Armonia prostheses (and the Magna to a lesser extent), the most distal cross-section was systematically greater than the inflow area, suggesting a divergent configuration at the systolic peak. CONCLUSION: The study results combined the fluid dynamic reproducibility of the in-vitro setting and the specificity of surgery. A quantitative comparison of the fluid dynamic performance of the different bioprostheses was feasible. PMID- 26897840 TI - Evaluation of p53 Polymorphism in Patients with Pannus-Derived Prosthetic Dysfunction. AB - BACKGROUND AND AIM OF THE STUDY: Prosthetic valve dysfunction (PVD) due to pannus formation is considered to occur due to a bioreaction to prosthetic material. The p53 gene plays a critical role in apoptosis and cell proliferation. p53 Arg72Pro polymorphism has been found to be associated with coronary stent restenosis, but has not yet been studied in prosthetic heart valve dysfunction. The study aim was to evaluate the association between pannus-derived PVD and p53 G72C(Arg72Pro) polymorphism. METHODS: This single-center, prospective study included 25 patients (20 females, five males; mean age 45.6 +/- 12.5 years; group 1) who underwent redo valve surgery due to PVD, and 49 age- and gender-matched control patients (44 females, five males; mean age 47.3 +/- 12.2 years; group 2) with normofunctional prostheses. The prostheses were examined using transthoracic and transesophageal echocardiography. Analyses of p53 G72C(Arg72Pro) polymorphism were performed using Roche LightCyler 2.0 Real-time polymerase chain reaction. RESULTS: The most common location of replaced valves was the mitral position in both groups (88% and 89.8%, respectively). In group 1, normal alleles (GG) were observed in 12 patients (48%), while one patient (4%) showed a homozygous mutation (GC) and 12 patients (48%) showed a heterozygous mutation (CC). In group 2, 21 patients (42.9%) had normal alleles (GG), while four (8.2%) had a homozygous mutation (CC) and 24 (48.9%) had a heterozygous mutation (GC). No significant difference was observed between the groups with regards to p53 Arg72Pro polymorphism (p = 0.769). CONCLUSION: In patients with prosthetic valves, the underlying mechanism behind pannus formation is unrelated to p53 Arg72Pro polymorphism. PMID- 26897841 TI - Expression and Localization of Granzymes and Perforin in Human Calcific Aortic Valve Disease. AB - BACKGROUND AND AIM OF THE STUDY: Calcified aortic valve disease (CAVD) is an actively regulated disease that shares pathophysiological hallmarks with atherosclerosis. One of these common features is extracellular matrix (ECM) remodeling, which consists of a dynamic degradation and deposition of the ECM composition. Granzymes (Grs) are ECM- degrading and pro-apoptotic proteases that have been detected in atherosclerotic lesions, but their role in CAVD remains unknown. METHODS: The expression of granzymes and perforin was characterized in heavily stenotic valves (n = 20) and control valves (n = 6) using quantitative RT PCR and immunohistochemistry. RESULTS: Quantitative RT-PCR revealed that levels of granzymes A, B, H, K and M mRNA were 4.9-fold (p < 0.001), 7.1-fold (p < 0.001), 4.6-fold (p < 0.001), 4.7-fold (p < 0.001) and 2.8-fold (p = 0.069) higher, respectively, in stenotic aortic valves than in control valves. Perforin mRNA levels were 3.6-fold (p < 0.001) higher in stenotic valves than in control valves. Granzyme A immunohistochemical positivity was observed in mast cells and lymphocytes, granzyme H in mast cells but not in lymphocytes, and granzyme K in lymphocytes but not in mast cells. A statistical analysis was also performed to investigate the effect of statin treatment on granzyme expression, but no differences were found when compared to non-statin-treated patients. CONCLUSIONS: The data acquired showed that CAVD is characterized by an increased expression of granzymes A, B, H, K, and perforin. PMID- 26897842 TI - Degenerative Calcification of Pericardial Bioprostheses: Comparison of Five Implantation Methods in a Rabbit Model. AB - BACKGROUND AND AIM OF THE STUDY: The degenerative calcification of bioprosthetic heart valves remains a clinical challenge, especially among young adults and children. Animal models that are based on subcutaneous and intramuscular implantation and are typically used to assess interventions to prevent bioprosthetic heart valve calcification do not reflect actual hemodynamic stress and lack direct blood contact. Thus, the study aim was to investigate bioprosthesis calcification at different implantation sites. METHODS: The calcification degrees of five valve implantation methods, namely subcutaneous, intramuscular and intravenous implantation, and arterial and venous patch angioplasty, were simultaneously investigated in 10 New Zealand White rabbits. RESULTS: Ultrasonography and computed tomography images showed vascular patency to be well maintained in all implanted vessels. Histologically, cellular infiltrates around the implant and within the collagen fibers were only found in the intravenous implantation group, which also had the highest calcium level among the methods. CONCLUSION: The present study was the first to compare the degree of calcification after applying five implantation methods simultaneously in one animal species. The rabbit intravenous implantation model, which involved direct contact with blood factors, is expected to serve as a useful animal model for research into the prevention of bioprosthetic heart valve degeneration. PMID- 26897843 TI - Heart Transplant in Patients with Predominantly Rheumatic Valvular Heart Disease. AB - BACKGROUND AND AIM OF THE STUDY: International records indicate that only 2.6% of patients with heart transplants have valvular heart disease. The study aim was to evaluate the epidemiological and clinical profile of patients with valvular heart disease undergoing heart transplantation. METHODS: Between 1985 and 2013, a total of 569 heart transplants was performed at the authors' institution. Twenty patients (13 men, seven women; mean age 39.5 +/- 15.2 years) underwent heart transplant due to structural (primary) valvular disease. Analyses were made of the patients' clinical profile, laboratory data, echocardiographic and histopathological data, and mortality and rejection. RESULTS: Of the patients, 18 (90%) had a rheumatic etiology, with 85% having undergone previous valve surgery (45% had one or more operations), and 95% with a normal functioning valve prosthesis at the time of transplantation. Atrial fibrillation was present in seven patients (35%), while nine (45%) were in NYHA functional class IV and eight (40%) in class III. The indication for cardiac transplantation was refractory heart failure in seven patients (35%) and persistent NYHA class III/IV in ten (50%). The mean left ventricular ejection fraction (LVEF) was 26.6 +/- 7.9%. The one-year mortality was 20%. Histological examination of the recipients' hearts showed five (27.7%) to have reactivated rheumatic myocarditis without prior diagnosis at the time of transplantation. Univariate analysis showed that age, gender, LVEF, rheumatic activity and rejection were not associated with mortality at one year. CONCLUSION: Among the present patient cohort, rheumatic heart disease was the leading cause of heart transplantation, and a significant proportion of these patients had reactivated myocarditis diagnosed in the histological analyses. Thus, it appears valid to investigate the existence of rheumatic activity, especially in valvular cardiomyopathy with severe systolic dysfunction before transplantation. PMID- 26897844 TI - Transcatheter Aortic Valve Implantation in Patients at Extremely High Risk of Perioperative Mortality. AB - BACKGROUND AND AIM OF THE STUDY: Transcatheter procedures are considered the therapy of choice for high-risk patients who are not eligible for surgical aortic valve replacement. Although its utility is debated, the logistic EuroSCORE I is still the most frequently used risk calculator for cardiac surgery in Europe, and was used in the present study to identify patients with an extremely high risk of predicted perioperative mortality. METHODS: This single-centre study included 319 consecutive patients who underwent transapical or transaortic transcatheter aortic valve implantation (TAVI) between September 2008 and December 2012. Combined hybrid procedures and transfemoral TAVI patients were excluded. Those patients predicted to have an excessively high risk of perioperative mortality (EuroSCORE >40%, n = 90) were compared to those with a lower calculated risk (EuroSCORE <40%, n = 229) with respect to perioperative complications, short-term mortality and major adverse cardiac and cerebrovascular events. RESULTS: The 30 day mortality was 12.2% (n = 11) in the extremely high-risk group, and 6.6% (n = 15) in the lower-risk group (p = 0.08). There were no significant differences in the stroke rate (3.3% versus 0.4%, p = 0.07) or the incidence of acute kidney injury stage 3 (11.1% versus 5.2%, p = 0.32). The establishment of cardiopulmonary bypass (3.9% versus 11.1%, p = 0.02), conversion to sternotomy (1.3% versus 5.6%, p = 0.04), mean ventilation time (15.2 h versus 43.5 h, p = 0.007) and length of intensive care unit stay (2.9 days versus 6.8 days, p <0.001) were all significantly lower in the lower-risk group. CONCLUSION: The data acquired verified that TAVI is a safe procedure, even in patients with an extremely high predicted risk of perioperative mortality and major adverse cardiac and cerebrovascular events. Furthermore, the analysis substantiated the need for individualized risk evaluation. PMID- 26897845 TI - Balloon-Expandable and Self-Expanding Transcatheter Heart Valves: Friend or Foe? AB - Transcatheter aortic valve replacement (TAVR) with balloon-expandable (BE) or self-expanding (SE) transcatheter heart valves (THVs) is indicated for the treatment of high-risk patients with severe aortic stenosis. Limited data are available comparing the two THV designs, and evidence suggests that each may offer unique advantages. Herein are described two patients who underwent TAVR with BE-THV and SE-THV, and who each developed a device-related complication that was successfully treated by using the alternate THV design. PMID- 26897847 TI - Transfemoral Treatment of a Paraprosthetic Mitral Leak and Mitral Bioprosthesis Failure Complicated by Embolization of In-Situ Vascular Plug. AB - Today, increasing numbers of patients are presenting to clinical teams with signs and symptoms of mitral bioprosthesis failure. Whilst redo surgery is currently the treatment option of choice, many patients have multiple co-morbidities and are deemed to be of prohibitively high surgical and anaesthetic risk. Percutaneous transcatheter treatment can offer a potential solution for these patients. Herein is reported a case where simultaneous transcatheter interventions for paraprosthetic leak and mitral bioprosthesis implantation were performed via the transfemoral route, and an unforeseen complication was successfully managed. PMID- 26897846 TI - Force Required to Cinch the Tricuspid Annulus: An Ex-Vivo Study. AB - BACKGROUND AND AIM OF THE STUDY: Tricuspid annuloplasty is the most preferred technique for the treatment of functional tricuspid regurgitation (FTR). However, high incidences of recurrent regurgitation and risky reoperation demands a deeper insight into the technique. The cinching force required to bring a dilated annulus back to the original size is unknown. The study aim was to quantify the cinching force in the tricuspid annulus which can contribute to the long-term durability of tricuspid annuloplasty and percutaneous device design. METHODS: In ten ovine hearts, a suture was anchored around the free wall of the tricuspid annulus with the free end attached to a force transducer. The force transducer was mounted on a slider system which pulled the suture at regular intervals. Closure of the tricuspid valve was achieved by pressurizing the right ventricle at 30 mmHg through the pulmonary valve. The suture was pulled to cinch the tricuspid annulus. The tricuspid annulus area was measured from images taken at each increment, and the corresponding force was recorded. The hearts were tested for three conditions: (i) non-pressurized (NP); (ii) pressurized (P; normal), and (iii) dilated-pressurized (DP; diseased). Leakage data were also collected for pressurized and dilated pressurized conditions. Annulus dilation was created by injecting phenol into the annulus. RESULTS: The maximum annulus dilation obtained was 8.82%, and the maximum cinching force was 0.38 +/- 0.09 N. Leakage was increased by 81.73% from the pressurized to dilated condition. CONCLUSION: The minimal force required to cinch a tricuspid annulus with severe FTR (23.98% dilation) can be approximated to 0.25 N. The required cinching force can play a major role in the long-term durability of the tricuspid annuloplasty. PMID- 26897848 TI - [Feasibility Study for Storage and Re-Utilization of Circulating Tumor Cells (CTCs)]. AB - BACKGROUND: In this era of precision medicine, monitoring patients requires not only real time but also longitudinal sequence of samples at various time points. Based on this background, we focused on conditioned circumstances on fixation and storage for re-utilization of CTCs. MATERIALS: Instead of actual CTCs, Cell line (H1975) derived from lung cancer was used because of their scarceness of CTCs. METHODS: These cells were put on a slide by using an auto-smear device. The slides were evaluated under various centrifuge forces, fixations for the following storages. RESULTS AND DISCUSSION: The study indicated that 800 rpm for 1 min centrifuge and fixation by 95% ETOH was excellent. Further at least 5 cells per 1 mL cell solution were required for the following procedures including Fluorescence in situ hybridization (FISH) analysis. This study provides insights of new platform for evaluation of CTCs not only real time but also longitudinal sequence at various time points. PMID- 26897849 TI - [KRAS Genetic Mutation Analysis Using the Clinical FFPE Samples of Colorectal Carcinomas: Comparative Study among 5 Methods]. AB - Targeting of epidermal growth factor receptor (EGFR) with monoclonal antibodies such as cetuximab or panitumumab inhibits the activation of downstream signaling molecules of EGFR. Since EGFR inhibitor therapy has been approved for the treatment of colorectal carcinomas in patients with tumors lacking KRAS mutations, the detection of KRAS mutation is indispensable before starting therapy. Although several laboratory procedures have been developed to detect KRAS mutations, few comparative studies of the sensitivity of mutation detection have been performed for such procedures. Here, we compared the levels of detection in 5 commercial KRAS mutation detection methods using both standard DNA samples and formalin-fixed clinical samples obtained during surgery. Scorpion ARMS assay has been reported as the most sensitive and we compared 4 other methods with Scorpion. Both PCR-rSSO assay and F-PHFA assay showed the highest concordance. As for the detection sensitivity, there were variations between clinical samples apparently due to sample quality or assay principles and methods. It is thus suggested that routine validation is required using samples prepared in each lab and the choice of assay may depend on various factors, such as lab environment, actual needs of physicians and patients, and the quality of the formalin-fixed specimens. PMID- 26897850 TI - [Strategy Development for International Cooperation in the Clinical Laboratory Field]. AB - The strategy of international cooperation in the clinical laboratory field was analyzed to improve the quality of intervention by reviewing documents from international organizations and the Japanese government. Based on the world development agenda, the target of action for health has shifted from communicable diseases to non-communicable diseases (NCD). This emphasizes the importance of comprehensive clinical laboratories instead of disease-specific examinations in developing countries. To achieve this goal, the World Health Organization (WHO) has disseminated to the African and Asian regions the Laboratory Quality Management System (LQMS), which is based on the same principles of the International Organization of Standardization (ISO) 15189. To execute this strategy, international experts must have competence in project management, analyze information regarding the target country, and develop a strategy for management of the LQMS with an understanding of the technical aspects of laboratory work. However, there is no appropriate pre- and post-educational system of international health for Japanese international workers. Universities and academic organizations should cooperate with the government to establish a system of education for international workers. Objectives of this education system must include: (1) training for the organization and understanding of global health issues, (2) education of the principles regarding comprehensive management of clinical laboratories, and (3) understanding the LQMS which was employed based on WHO's initiative. Achievement of these objectives will help improve the quality of international cooperation in the clinical laboratory field. PMID- 26897851 TI - [A Perspective on Innovation for Efficient Medical Practice in View of Undergraduate and Postgraduate Education and Training in Laboratory Medicine]. AB - Continuous advances in medical laboratory technology have driven major changes in the practice of laboratory medicine over the past two decades. The importance of the overall quality of a medical laboratory has been ever-increasing in order to improve and ensure the quality and safety of clinical practice by physicians in any type of medical facility. Laboratory physicians and professional staff should challenge themselves more than ever in various ways to cooperate and contribute with practicing physicians for the appropriate utilization of laboratory testing. This will certainly lead to a decrease in inappropriate or unnecessary laboratory testing, resulting in reducing medical costs. In addition, not only postgraduate, but also undergraduate medical education/training systems must be markedly innovated, considering recent rapid progress in electronic information and communication technologies. PMID- 26897852 TI - [Standardization and Quality Assurance in Laboratory Medicine]. AB - The standardization of clinical laboratory and compatible clinical data is needed for accurate diagnosis in routine medical practice or medical care. An external quality survey program (EQSP) in clinical laboratory testing and recommendation methods for laboratory test and/or standard materials are proposed. Many megaEQSPs in Japan have problems, such as examination samples (matrix and spike materials in abnormal specimens) and valuation basis. Proposals for EQSP are being developed: EQSP with fresh blood, EQSP using internal quality control, and control serum using donated blood (MaCRM). PMID- 26897853 TI - [Personalized Medicine in Rheumatoid Arthritis]. AB - Medical strategy for rheumatoid arthritis (RA) has markedly advanced in recent years. The introductions of biologics and methotrexate as an anchor drug have made it possible to not only suppress pain and inflammation (clinical remission), but also to inhibit joint destruction (structural remission), leading to cure of the disease. In order to achieve this target, it is the most important to diagnose RA early and promote disease remission. However, since the condition and pathology are diverse among patients, optimal treatment for each patient is desired (personalized medicine). Treatment should be performed under consideration of the disease state such as activity, prognosis regarding joint destruction, and complications. It is also important to clarify the patient characteristics, such as responsiveness to the drugs and risk of adverse effects. Biomarkers, such as proteomics and pharmacogenomics (genetic polymorphism, etc.), are indispensable for personalized medicine. We have established a predictive model for methotrexate hepatotoxicity, consisting of 13 SNPs with a sensitivity of 100% and specificity of 89%, although the model should be validated with a larger-scale prospective study. RA is a multifactorial disorder with clinically heterogeneous features. Gene-environment interaction is closely involved in the production of anti-CCP antibodies (ACPA); thereafter, secondary stimuli of joints may lead to symptoms of RA. Joint injury, emotional stress, and infections often trigger the onset of RA. Cure can be achieved through complete remission by early aggressive treatment and returning to the pre-clinical state of RA with environmental improvement. PMID- 26897854 TI - [The Laboratory Medicine of Lipid Mediators]. AB - Lysophospholipids such as lysophosphatidic acid (LPA), sphingosine 1-phosphate (S1P), and lysophosphatidylserine (LysoPS) are attracting attention as second generation lipid mediators. We have pursued the clinical introduction of the assays of lysophospholipids and related proteins, and in this review, the clinical application of the assay of LPA and autotaxin(ATX), which produces LPA from lysophosphatidylcholine through its lysophospholipase D activity, is mainly described. The assay of ATX is promising as a useful laboratory test, especially for the diagnosis and staging of liver fibrosis PMID- 26897855 TI - [Molecular-Genetic Diagnosis and Molecular-Targeted Therapy in Cancer: Challenges in the Era of Precision Medicine]. AB - Elucidation of the molecular pathogenesis of neoplasms and application of emerging technologies for testing and therapy have resulted in a series of paradigm shifts in patient care, from conventional to personalized medicine. This has been promoted by companion diagnostics and molecular targeted therapy, tailoring the treatment to the individual characteristics of each patient. Precision oncology has been accelerated by integrating the enhanced resolution of molecular analysis, mechanism clarity, and therapeutic relevance through genomic knowledge. In its clinical implementation, there are laboratory challenges concerning accurate measurement using stored samples, differentiation between driver and passenger mutations as well as between germline and somatic mutations, bioinformatics availability, practical decision-making algorithms, and ethical issues regarding incidental findings. The medical laboratory has a new role in providing not only testing services but also an instructive approach to users to ensure the sample quality and privacy protection of personal genome information, supporting the quality of patient practice based on laboratory diagnosis. PMID- 26897856 TI - [Genetic Diagnosis and Molecular Therapies for Duchenne Muscular Dystrophy]. AB - Duchenne muscular dystrophy (DMD) is the most common form of inherited muscle disease and is characterized by progressive muscle wasting, ultimately resulting in the death of patients in their twenties or thirties. DMD is characterized by a deficiency of the muscle dystrophin as a result of mutations in the dystrophin gene. Currently, no effective treatment for DMD is available. Promising molecular therapies which are mutation-specific have been developed. Transformation of an out-of-frame mRNA into an in-frame dystrophin message by inducing exon skipping is considered one of the approaches most likely to lead to success. We demonstrated that the intravenous administration of the antisense oligonucleotide against the splicing enhancer sequence results in exon skipping and production of the dystrophin protein in DMD case for the first time. After extensive studies, anti-sense oligonucleotides comprising different monomers have undergone clinical trials and provided favorable results, enabling improvements in ambulation of DMD patients. Induction of the read-through of nonsense mutations is expected to produce dystrophin in DMD patients with nonsense mutations, which are detected in 19% of DMD cases. The clinical effectiveness of gentamicin and PTC124 has been reported. We have demonstrated that arbekacin-mediated read-through can markedly ameliorate muscular dystrophy in vitro. We have already begun a clinical trial of nonsense mutation read-through therapy using arbekacin. Some of these drug candidates are planned to undergo submission for approval to regulatory agencies in the US and EU. We hope that these molecular therapies will contribute towards DMD treatment. PMID- 26897858 TI - [Pathogenesis and Clinical Examination of Autoinflammatory Syndrome]. AB - Autoinflammatory syndrome is characterized by: 1) episodes of seemingly unprovoked inflammation, 2) the absence of a high titer of autoantibodies or auto reactive T cells, and 3) an inborn error of innate immunity. In this decade, many autoinflammatory syndromes have been reported in Japan, and so many Japanese physicians have become aware of this syndrome. Monogenic autoinflammatory syndromes present with excessive systemic inflammation including fever, rashes, arthritis, and organ-specific inflammation and are caused by defects in single genes encoding proteins that regulate innate inflammatory pathways. The main monogenic autoinflammatory syndromes are familial Mediterranean fever (FMF), TNF receptor-associated periodic syndrome (TRAPS), mevalonate kinase deficiency (MKD), cryopyrin-associated periodic syndrome (CAPS), Blau syndrome, and syndrome of pyogenic arthritis with pyoderma gangrenosum and acne (PAPA). We diagnosed these syndromes as clinical manifestations and performed genetic screening. Many serum cytokines are elevated in patients with autoinflammatory syndrome, but this is not disease-specific. The pathogeneses of many autoinflammatory syndromes are known to be related to inflammasomes, which are multiprotein complexes that serve as a platform for caspase 1 activation and interleukin-1beta(IL-1beta) and IL-18 maturation. Especially, NLRP3 inflammasomes may play a crucial role in the initiation and progression of FMF and CAPS. Recently, it was reported that NETs (neutrophil extracellular traps) derived from neutrophils may also play an important role in the pathogenesis of FMF. In the future, we hope to discover new clinical examinations which can provide evidence of inflammasome activation independent of genetic screening. In this issue, I introduce autoinflammatory syndromes and discuss the pathogenesis and clinical examination of these syndromes. PMID- 26897857 TI - [Pathophysiology and Assessment of IgG4-Related Disease--Focus on Autoimmune Pancreatitis]. AB - IgG4-related disease is well-known, and while the functions of cytokines which affect IgG4 production are being clarified, it remains unclear what causes it. There are many clinicopathological characteristics of IgG4-related disease and, therefore, comprehensive criteria are used for diagnosis. Notably, histopathological findings are the most important of these, with which we cannot make a definite diagnosis. The model disease of an IgG4-related disease is autoimmune pancreatitis (AIP). Currently, AIP is classified into type 1 (AIP1) and type 2 (AIP2). AIP1 is IgG4-related while AIP2 is not. AIP1 sometimes has localized mass formation, making it difficult to distinguish between AIP1 and pancreatic cancer. Thus, upon biochemical and immunological examination, the IgG4 level is the most useful for the diagnosis, although the levels of IL-2R, beta2MG, C4, and monoclonal rheumatoid factor are also useful for the assessment of disease. In addition, histopathological findings are also important to diagnose AIP1. Typical AIP1 cases show lymphoplasmacytic infiltration including IgG4-positive plasma cells with storiform fibrosis. A careful analysis of cases with the typical features of IgG4-related disease will lead to the elucidation of the mechanism behind IgG4-related disease. PMID- 26897859 TI - [Pathophysiology and Laboratory Findings in Patients with ANCA-Associated Vasculitis]. AB - Pathophysiological features and laboratory findings in patients with anti neutrophil cytoplasmic antibody (ANCA) -associated vasculitis are described. In contrast to Western countries, MPO-ANCA-positive microscopic polyangiitis and renal-limited vasculitis is the most common form of ANCA-associated vasculitis in Japanese patients. Oral prednisolone in combination with immunosuppressive agents has improved patient survival in older Japanese patients. However, the recurrence rate has significantly increased in recent years Accumulative evidence supports a direct pathogenic role of ANCA in glomerulonephritis and vasculitis, in which inflammatory processes with the up-regulation of cytokines/chemokines and possible involvement of a neutrophil extracellular trap may play a role. However, whether or not the measurement of ANCA titers reflects disease activity and predicts the onset and/or relapse of ANCA-associated vasculitis remains controversial. Further studies will be required to determine the clinical significance of ANCA in more detail. In addition to ANCA, measurements of novel clinical test items, including anti-erythropoietin receptor antibody, may reveal the possibility of their application as useful biomarkers of the pathophysiology and clinical manifestations in patients with ANCA-associated vasculitis. PMID- 26897860 TI - [Pathogenesis and Laboratory Findings in Antiphospholipid Syndrome, Especially Associated with Lupus Anticoagulant]. AB - Antiphospholipid syndrome (APS), an acquired thrombotic condition, is a complex clinical state characterized by the presence of circulating antiphospholipid antibodies in patients with thrombosis or pregnancy morbidity. Revised APS classification criteria are used for diagnosis, which include at least one clinical criterion (thrombosis or pregnancy loss) and at least one of the laboratory criteria [anticardiolipin antibodies, anti-beta2GPI antibodies, lupus anticoagulant (LA)]. LA is also an independent risk factor for developing thrombosis, though some LA-positive cases have been reported to have a bleeding symptom. Lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS) is a rare disorder characterized by a bleeding tendency due to low prothrombin activity in patients with LA, and has recently been reported not only in children but also in adults We have encountered LA cases with bleeding and low coagulation factor activities except for prothrombin. Based on our findings, we propose that LA positive cases with a bleeding symptom and characterized by low coagulation factor activity including prothrombin be termed lupus anticoagulant-associated coagulopathy (LAAC). Furthermore, coagulation factor autoantibodies are often detected in LAAC patients; thus, correct measurement of LA is important to distinguish LAAC patients from those possessing an inhibitor to coagulation factors such as acquired hemophilia A as well as to select the optimal therapeutic strategy. PMID- 26897862 TI - Editorial. PMID- 26897861 TI - [Thrombotic Thrombocytopenic Purpura --Pathophysiology and Assays of ADAMTS13 Activity]. AB - Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disorder classified with a type of thrombotic microangiopathy (TMA). TTP is caused by a deficiency of von Willebrand factor-cleaving protease called ADAMTS13 (a disintegrin-like and metalloprotease with a thrombospondin type1 motif 13). Low ADAMTS13 levels result in increased ultra-large von Willebrand factor multimers (UL-VWFM), which induce platelet adhesion and thrombosis. Congenital TTP (Upshaw Schulman syndrome: USS) is an inherited disorder of ADAMTS13, and the other more commonly is an acquired TTP caused by autoantibodies against ADAMTS13. This article reviews the progress of ADAMTS13 activity measurement and the resulting changes in the diagnosis and treatment of TTP. PMID- 26897863 TI - Towards an optimal multidisciplinary approach to breast cancer treatment for older women. AB - The treatment of breast cancer presents specifc concerns that are unique to the needs of older female patients. While treatment of early breast cancer does not vary greatly with age, the optimal management of older women with breast cancer often requires complex interdisciplinary supportive care due to multiple comorbidities. This article reviews optimal approaches to breast cancer in women 65 years and older from an interdisciplinary perspective. A literature review was conducted using MEDLINE and EMBASE, choosing articles concentrated on the management of older breast cancer patients from the point of view of several disciplines, including geriatrics, radiation oncology, medical oncology, surgical oncology, psychooncology, palliative care, nursing, and social work. This patient population requires interprofessional collaboration from the time of diagnosis, throughout treatment and into the recovery period. Thus, we recommend an interdisciplinary program dedicated to the treat ment of older women with breast cancer to optimize their cancer care. PMID- 26897864 TI - An evaluation report of the nurse navigator services for the breast cancer support program. AB - The purpose of this quality improvement project was to evaluate the effectiveness of breast cancer care support provided by breast cancer care navigators (BCCN) for women attending the breast health clinic (BHC). This evaluative process examined patients' satisfaction with the nurse navigator program that focused on addressing breast cancer patients' informational needs, emotional support, and guidance through the cancer trajectory. A survey approach using Likert-type scales and open-ended questions was utilized to gather data. Patients seen at the BHC between July 2011 and July 2013 were sent the surveys by mail. The 154 responses constituted a 69% response rate. More than 90% of participants understood the information provided by the BCCN and were satisfied with the information that had been received. Psychosocial support from patient/family counselling services at the agency and in the community were among the most common request for resources. Recommendations include contacting patients directly after their initial meeting at the clinic and at least once after their treatments began, to ensure continuity and support. BCCN role was identified as being valuable with a positive effect on patients' experience. PMID- 26897865 TI - Perceived roles of oncology nursing. AB - The Canadian Association of Nurses in Oncology (CANO) Standards of Care (2001) provides a framework that delineates oncology nursing roles and responsibilities. The purpose of this study was to explore how oncology nurses perceive their roles and responsibilities compared to the CANO Standards of Care. Six focus groups were conducted and 21 registered nurses (RNs) from a community-based hospital participated in this study. Transcripts were analyzed using qualitative inductive content analysis. Three themes were identified: (1) Oncology nurses perceive a gap between their defined roles and the reality of daily practice, as cancer care becomes more complex and as they provide advanced oncology care to more patients while there is no parallel adaptation to the health care system to support them, such as safe staffing; (2) Oncology nursing, as a specialty, requires sustained professional development and leadership roles; and (3) Oncology nurses are committed to providing continuous care as a reference point in the health care team by fostering interdisciplinary collaboration andfacilitating patient's navigation through the system. Organizational support through commitment to appropriate staffing and matching scope ofpractice to patient needs may lead to maximize the health and well-being of nurses, quality of patient care and organizational performance. PMID- 26897866 TI - The role of biosimilar granulocyte colony stimulating factor (GCSF) Zarzio for progenitor cell mobilization and the treatment of therapy-induced neutropenia in adult hematopoietic stem cell transplantation. AB - Originator GCSF (Neupogen) has been used to mobilize progenitor stem cells and treat therapy-induced neutropenia in Canadian stem cell transplant settings for years. Although its benefit is not in question, viable alternatives are available. Biosimilar GCSF (Zarzio) is widely in use in Europe since 2009 and was recently approved in the U.S.for the same five indications as Neupogen. Zarzio is reported as safe, equally efficacious, more accessible and cost effective without negatively impacting patient outcomes. This paper summarizes the supporting evidence. PMID- 26897867 TI - Engaging patients using an interprofessional approach to shared decision making. AB - Many cancer treatment and screening decisions are difficult given that they rely upon patients' informed preferences. Interprofessional shared decision making is when two or more health care professionals collaborate with a patient to reach an agreed-upon decision. To support patients' engagement in shared decision making, effective interventions include patient decision aids and/or decision coaching. Patient decision aids are typically written or video-based resources, while decision coaching is provided by trained health care professionals who are supportive but non-directive. Both interventions make explicit the decision, provide balanced information on options based on the best available evidence, and help patients consider what matters most. The overall aim is to discuss how oncology nurses can engage in an interprofessional approach to shared decision making. PMID- 26897868 TI - The burden of caring. PMID- 26897869 TI - e-Mentorship: Navigation strategy for promoting oncology nurse engagement in research. AB - There is a high need for research mentorship among Canadian oncology nurses. E mentorship is an effective vehicle for linking oncology nurses with experienced researchers across the country who can help them navigate the road and increase their engagement in research. E-mentorship also has the potential to build research capacity more broadly by strengthening national networks and connections among researchers, cancer care organizations and oncology nurses at the point of care. Innovative strategies are needed to more easily identify and recruit researchers who are committed to advancing oncology nursing practice through effective mentorship. PMID- 26897870 TI - Research mentoring for oncology nurses in clinical settings: For whom, why, and how? PMID- 26897871 TI - Partnering with oncology nursing leaders in Latin America to deliver an education program on oral therapies in cancer. PMID- 26897872 TI - Highlights from an International Panel on Cancer Nursing and Care. PMID- 26897873 TI - Nurse to Know: Charrisa Cordon. PMID- 26897874 TI - PREPARING FOR THE COMING STORM. PMID- 26897875 TI - A LETTER FROM THE DMU WHITE COAT CEREMONY. PMID- 26897876 TI - IMS BOARD APPROVES 2016 LEGISLATIVE AGENDA. PMID- 26897877 TI - IBM, IBPA TO ESTABLISH PA SUPERVISION DEFINITION, STANDARDS BY FEBRUARY 1. PMID- 26897878 TI - COMING THIS SPRING... PMID- 26897879 TI - POLICY FORUM RESULTS. PMID- 26897880 TI - STATE LICENSURE OF GENETIC COUNSELORS. PMID- 26897881 TI - AT RISK: ONE MINUTE 45 SECONDS. PMID- 26897882 TI - 2015 IOWA PHYSICIAN SURVEY: WHAT WE LEARNED. PMID- 26897883 TI - What's in a name? PMID- 26897884 TI - More tips for promoting health equity. PMID- 26897885 TI - Martial arts master. PMID- 26897886 TI - Med students honor choices. PMID- 26897887 TI - Cannabis and chronic pain. PMID- 26897888 TI - Misunderstood specialty. PMID- 26897889 TI - Small comforts. Children's hospitals add palliative care. PMID- 26897890 TI - Life and death in Alzheimer's disease. PMID- 26897891 TI - Early adopter. PMID- 26897892 TI - Round two: MMA gears up for another prior auth legislative push. PMID- 26897893 TI - Questions about medical cannabis linger. PMID- 26897894 TI - Minnesota's Right to Try law. PMID- 26897895 TI - We need to end the paper trail. PMID- 26897896 TI - Having a Meaningful Conversation with Patients about the End of Life: Six Tips for Physicians. PMID- 26897897 TI - Palliative Care in Rural Minnesota: Findings from Stratis Health's Minnesota Rural Palliative Care Initiative. AB - Palliative care, which involves managing symptoms, controlling pain and addressing stress caused by a chronic or terminal illness, has been shown to keep patients out of the hospital and allow them to stay home and live more comfortably with their illness. Typically, it is provided by an interdisciplinary team led by a physician trained in palliative medicine. Rural areas have not always had access to such specialists. Yet, today, rural health care organizations are finding ways to create palliative care programs that meet the needs of their chronically ill and aging populations. This article describes a six-year initiative led by Stratis Health to advance palliative care in rural Minnesota. It highlights the work of FirstLight Health System in Mora and describes Stratis Health's Rural Palliative Care Measurement Pilot Project, an effort to develop and test measures for evaluating rural palliative care programs. PMID- 26897898 TI - USPSTF Recommendations--2015 Update: Use in Primary Care and Other Practices. AB - Each year, the U.S. Preventive Services Task Force makes recommendations on the preventive services the nation's doctors and other health care providers should offer their patients. Although clinicians may be aware of these recommendations, they may not always know how best to implement them in practice. This article provides an explanation of how the Task Force arrives at its decisions and what its recommendations mean. It highlights recent changes to recommendations that represent significant changes for practice, and presents cases illustrating ways to apply the recommendations to individual patients. PMID- 26897899 TI - My Microbiome and Me. PMID- 26897900 TI - The Dilemma Dilemma. PMID- 26897902 TI - Periodontics and Oral-Systeric Relationships: Diabetes. AB - The oral cavity is a part of the body. The health of the oral cavity affects the health of the entire body. This relationship is reciprocal, as the overall health of an individual will also affect the health of that individual's oral cavity. Periodontal disease is a common, chronic inflammatory disease affecting the supporting structures of the teeth. It has been proposed that periodontal disease is a risk factor for systemic diseases such as diabetes. PMID- 26897903 TI - Atypical Presentation of Zoster Mimicking Headache and Temporomandibular Disorder: A Case Report. AB - Herpes zoster in the prodromal stage may be mistaken for other diseases characterized by pain in the area of prodrome, such as dental pain. We report on a case of trigeminal herpes zoster, which presented as sudden onset headache and acute temporomandibular pain in the prodromal phase. PMID- 26897904 TI - A National Survey of Positional Leadership Trajectories of U.S. Dentists. AB - An electronic survey was responded to by 233 fellows of the American College of Dentists and by 586 graduates of four dental schools. Rate of involvement and weighted number of leadership positions held gradually increased until about age 45 to 50, then declined more steeply. Leadership potential manifested itself as early as dental school and the characteristics most associated with leadership were professionalism and a strong ethic, while available time and personal sacrifice were not regarded as great drawbacks. PMID- 26897901 TI - UCSF Protocol for Caries Arrest Using Silver Diamine Fluoride: Rationale, Indications and Consent. AB - The Food and Drug Administration recently cleared silver diamine fluoride for reducing tooth sensitivity. Clinical trials document arrest and prevention of dental caries by silver diamine fluoride. This off-label use is now permissible and appropriate under U.S. law. A CDT code was approved for caries arresting medicaments for 2016 to facilitate documentation and billing. We present a systematic review, clinical indications, clinical protocol and consent procedure to guide application for caries arrest treatment. PMID- 26897905 TI - Top Seven Data Breach Considerations. PMID- 26897906 TI - HIPAA Security Rule Technical Safeguards. PMID- 26897907 TI - Protest Now. PMID- 26897908 TI - High Prevalence of Male Infertility in Africa: Are Mycotoxins to Blame? PMID- 26897909 TI - The Ebola Virus and Human Rights Concerns in Africa. AB - In the wake of the Ebola virus disease (EVD) that is ravaging parts of Africa certain measures are being taken by governments to prevent the spread of the epidemic within their borders. Some of these measures are drastic and may likely have implications for the fundamental rights of individuals. The EVD outbreaks have brought to the fore again the tension between public health and human rights. This article discusses the origin and mode of transmission of the EVD and then considers the human rights challenges that may arise as a result of states' responses to the disease in Africa. PMID- 26897910 TI - Managing Caesarean Scar Pregnancy in low Resource Settings: 2 Case Reports and a Description of Transrectal Ultrasound guided Surgical Approach (TRUGA). AB - Caesarean scar pregnancy (CSP) occurs when an embryo implants in a previous caesarean section scar. It has a reported incidence of 1 in 1800. Various surgical and medical techniques have been described in case reports for the management of CSP. These techniques are usually undertaken in tertiary level units with significant resource availability. In this paper, we present a new clinical perspective for the management of CSP in low resource settings and describe the steps involved in a transrectal ultrasound guided approach with dilatation of uterine cervix and subsequent evacuation of uterine contents (TRUGA with D&C). PMID- 26897911 TI - Female Genital Mutilation: A Literature Review of the Current Status of Legislation and Policies in 27 African Countries and Yemen. AB - This article discusses the results of a literature review that has assessed the impact of Female Genital Mutilation (FGM) legislation in 28 countries (27 in Africa and Yemen) where FGM is concentrated. Evidence on the impact of FGM legislation was available on prevalence of FGM; changes in societal attitudes and perceptions of FGM; knowledge and awareness of FGM legislation and consequences, and the impact on medicalization. While the majority of countries have adopted legal frameworks prohibiting FGM, these measures have been ineffective in preventing and/or in accelerating the abandonment of the practice. Anti-FGM laws have had an impact on prevalence in only two countries where strict enforcement of legal measures has been complemented by robust monitoring, coupled with robust advocacy efforts in communities. Owing to poor enforcement and lax penalties, legal measures have had a limited impact on medicalization. Similarly, legal frameworks have had a limited impact on societal attitudes and perceptions of FGM, with evidence suggesting rigid enforcement of FGM laws has in some instances been counterproductive. Although evidence suggests legislation has not influenced the decline in FGM in the majority of countries, legal frameworks are nevertheless key components of a comprehensive response to the elimination and abandonment of the practice, and need to be complemented by measures that address the underlying socio-cultural norms that are the root of this practice. PMID- 26897912 TI - Men's Attitudes Towards Contraception in Sub-Saharan Africa. AB - This paper examines male attitudes towards family planning in Sub-Saharan Africa. Studying attitudes is ideal as they can be calculated for all men, at any point in their lives, regardless of marital status, sexual activity, or fertility desires. We find that positive attitudes towards family planning have increased across Sub-Saharan Africa in the last two decades. We analyze both the association of positive attitudes with a variety of demographic characteristics (age, marital status, education, and religion) and the relationships with multiple forms of discussion about family planning (radio, television, friends, and partners). We find higher approval at older ages and higher levels of education, and lower levels of approval among Muslims compared to Christians. Interactions between characteristics and discussion of family planning. demonstrate that hearing or talking about contraception has different associations for different groups. This paper offers a new way to explore fertility and reproductive health in Sub-Saharan Africa. PMID- 26897913 TI - Knowledge of School Health Programme among Public Primary School Teachers in Oyo State, South-West Nigeria: A Rural-Urban Comparative Study. AB - Teachers are in a vantage position to facilitate positive health among school-age children through the School Health Programme (SHP). Lack of basic knowledge of the programme among them will hinder its effective implementation. Studies to gauge teachers' knowledge of SHP are needed to improve the current suboptimal level of implementation in Nigeria. This study was conducted to assess and compare the knowledge of SHP among public primary school teachers in rural and urban areas of Oyo State, South-West Nigeria. A comparative cross-sectional survey was conducted among teachers in selected rural and urban public primary schools using a 2-stage cluster sampling technique. Knowledge scores were computed giving minimum and maximum obtainable scores of 0 and 33 respectively. Respondents were reported as having inadequate knowledge if aggregate score "was <16.5 and adequate if >= 16.5. Associations were tested using Chi-square and t test for qualitative and quantitative variables respectively at p = 0.05. Majority (84.6%) of the teachers had inadequate knowledge of SHP with similar proportions in the rural (84.2%) and urban (84.9%) schools. Higher proportions of those aged 40 years, that were ever married and had 2 qualifications had adequate knowledge compared with their counterparts (p < 0.05). Majority of the teachers had inadequate knowledge of SHP. Further study to assess teachers' training in SHP is needed. This may inform training intervention to upgrade their knowledge of the programme in the study area. PMID- 26897914 TI - Quality Indicators and Outcomes of Emergency Caesarean Deliveries at a District level Maternity Hospital. AB - The objective of this research study is to identify quality indicators of cesarean deliveries and determine their relationship to neonatal and maternal morbidity and mortality in one high volume maternity hospital in Lilongwe, Malawi. Demographic, perioperative, and postoperative data were collected on all cesarean deliveries over three months. Indicators of quality (antibiotic administration, use of oxytocin, decision-to-incision time, and uterine incision type) were compared to maternal morbidities (postpartum hemorrhage, fistula and wound infection) and neonatal mortality. Causes of delays in decision to incision time were identified. 513 cesarean deliveries were performed during the study period, with no maternal deaths and 39 neonatal deaths. Adherence to oxytocin and antibiotic administration was high but not complete, with greater adherence to the former (97.1% vs 82.6%). The decision to incision time between women with and without neonatal deaths was similar (1.62 hours vs 1.49 hours, p = 0.41). Most delays were attributed to a busy operating theatre (49.1%) and delayed transfer to the operating theatre (26.9%). Uterine rupture and cesarean hysterectomy were associated with an outcome of neonatal death (p < 0.001). Infrastructure and personnel limitations are major barriers to the improvement of quality of cesarean deliveries. Future endeavors towards quality improvement must address these deficiencies. PMID- 26897915 TI - Quality of Care: A Review of Maternal Deaths in a Regional Hospital in Ghana. AB - The government of Ghana and key stakeholders have put into place several interventions aimed at reducing maternal deaths. At the institutional level, the conduct of maternal deaths audit has been instituted. This also contributes to reducing maternal deaths as shortcomings that may have contributed to such deaths could be identified to inform best practice and forestall such occurrences in the future. The objective of this study was to review the quality of maternal care in a regional hospital. A review of maternal deaths using Quality of Care Evaluation Form adapted from the Komfo Anokye Teaching Hospital (KATH) Maternal Death Audit Evaluation Committee was used. About fifty-five percent, 18 (55%) of cases were deemed to have received adequate documentation, senior clinicians were involved in 26(85%) of cases. Poor documentation, non-involvement of senior clinicians in the management of cases, laboratory related issues particularly in relation to blood and blood products as well as promptness of care and adequacy of intensive care facilities and specialists in the hospital were contributory factors to maternal deaths . These are common themes contributing to maternal deaths in developing countries which need to be urgently tackled. Maternal death review with emphasis on quality of care, coupled with facility gap assessment, is a useful tool to address the adequacy of emergency obstetric care services to prevent further maternal deaths. PMID- 26897916 TI - Inter-Pregnancy Intervals and Maternal Morbidity: New Evidence from Rwanda. AB - The effects of short and long pregnancy intervals on maternal morbidity have hardly been investigated. This research analyses these effects using logistic regression in two steps. First, data from the Rwanda Demographic and Health Survey 2010 are used to study delivery referrals to District hospitals. Second, Kibagabaga District Hospital's maternity records are used to study the effect of inter-pregnancy intervals on maternal morbidity. The results show that both short and long intervals lead to higher odds of being referred because of pregnancy or delivery complications. Once admitted, short intervals were not associated with higher levels of maternal morbidity. Long intervals are associated with higher risks of third trimester bleeding, premature rupture of membrane and lower limb edema, while a higher age at conception is associated with lower risks. Poor women from rural areas and with limited health insurance are less often admitted to a hospital, which might bias the results. PMID- 26897917 TI - Addressing the Sexual and Reproductive Health Needs of Young People in Ethiopia: An Analysis of the Current Situation. AB - Young people in Ethiopia face a number of risks to their sexual and reproductive health, including adolescent pregnancy, sexual violence, and unmet need for family planning. This study explores the extent to which current service provision addresses the SRH needs of young Ethiopians . Methods included a comprehensive review of the academic and policy literature on young people's SRH and service provision in Ethiopia; and 14 semi-structured Key Informant Interviews. Factors affecting utilization of sexual and reproductive services by young people include: limited SRH knowledge, lack of open discussion of sexual matters, low status of women, cultural and logistical barriers, competing priorities among community health professionals, limited resources for health facilities, and negative attitudes of providers towards unmarried youth. While the antenatal needs of young married women are somewhat addressed, gaps exist in terms of services for unmarried youth, young men, rural youth and vulnerable groups. The national policy platform has created an enabling environment for addressing youth SRH needs but challenges to implementing these policies still persist. The way forward requires a focus on reducing barriers to utilization of services, and attention to underserved groups. It also requires resource mobilization, strong leadership and effective coordination between stakeholders and donors. PMID- 26897918 TI - Media Influence on Sexual Activity and Contraceptive Use: A Cross Sectional Survey among Young Women in Urban Nigeria. AB - This study assessed the relationship between recent exposure to family planning (FP) messages in the media (newspaper, radio, television, and mobile phones) and use of modern contraceptive methods among women aged 15-24 years living in six cities in Nigeria. Logistic regression models were used to predict recent media exposure to FP messages and its association with sexual experience and modern contraceptive method use. About 45% of our sample had ever had sex with only a quarter of them using a modern contraceptive method at the time of survey. Approximately 71% of our sample was exposed to FP messages in the media within the three months preceding the survey. The main sources of media exposure were mobile phones (48%), radio (37%), and television (29%). Controlling for relevant factors, recent media exposure to FP messages predicted both sexual experience and use of modern contraceptive methods, although there were city-level differences. PMID- 26897919 TI - The Other Side of Rapport: Data Collection Mode and Interviewer Gender Effects on Sexual Health Reporting in Ghana. AB - Accurate data on young people's sexual behaviour and sexual health practice is essential to inform effective interventions and policy. However, little empirical evidence exists to support methodological design decisions in projects assessing young people's sexual health, especially in African contexts. This short report uses original empirical data collected in Ghana in 2012 to assess the effects of data collection mode and interviewer gender on young people's reporting of sexual health and access to supportive sexual health resources. The findings indicate that the effect of data collection mode may vary by gender, and there is no indication of an interviewer gender effect for males in this study. Preliminary results suggest that building strong rapport with research participants in this context may lead to reduced sexual health data quality. These findings merit further investigation and have direct implications for the design of projects measuring sexual health and related variables in Ghana. PMID- 26897920 TI - Evaluating Health Workers' Knowledge Following the Introduction of Clinical Mentoring in Jigawa State, Northern Nigeria. AB - Clinical mentoring is work-based training for the capacity building of health care workers. This study determined if there were benefits and increases in knowledge levels for 33 selected health workers across 5 health facilities in Jigawa State following the introduction of clinical mentoring. Questionnaires were used to determine biodata and knowledge scores of mentored health workers and also key departmental activities before and after a 6 months period of introduction of clinical mentoring. Data was analyzed with SPSS version 20. Over 90% of the 33 mentored health workers showed an increase in their knowledge scores. The mean percentage score of the health workers increased significantly from 56.3 +/- 2.1 before the start of clinical mentoring to 74.7 +/- 1.7 (p < 0.001) six months later. Mortality review meetings were also introduced. This study has shown that clinical mentoring is beneficial for improving the clinical knowledge of mentored health workers. PMID- 26897921 TI - Evaluation of a Sexual and Reproductive Health Education Programme: Students' Knowledge, Attitude and Behaviour in Bolgatanga Municipality, Northern Ghana. AB - Evaluation research concerning the impact of sexual and reproductive health (SRH) education in sub-Saharan Africa is scarce. This study obtained more insight into the knowledge, attitudes and behavioural intentions of students concerning SRH in Bolgatanga municipality in northern Ghana, and studied the effects of an SRH programme for this group. This quasi-experimental study used a pre-post intervention design, with an SRH programme as intervention. A questionnaire was filled in by 312 students before, and by 272 students after the SRH programme. The results showed that before the programme, students answered half of the knowledge questions correctly, they thought positively about deciding for themselves whether to have a relationship and whether to have sex, and their intentions towards SRH behaviour, such as condom use were positive. The SRH intervention led to a small but significant increase in the students' knowledge. It was also found that the attitude of the students aged 18-20 significantly improved. Finally, it was found that female students aged 18-20 were more positive towards changing their behaviour after following the SRH programme. It can be concluded that the impact of the SRH programme in general was positive. Significant effects were found for gender and age. PMID- 26897922 TI - The Prevalence of Human Immunodeficiency Virus Infection among Pregnant Women in Labour with Unknown Status and those with Negative Status Early in the Index Pregnancy in a Tertiary Hospital in Nigeria. AB - Rapid HIV test in labour provide an opportunity for the identification of HIV positive pregnant women who should benefit from interventions to reduce the risk of mother-to-child transmission (MTCT) of HIV. Between November 2013 and June 2014 we conducted rapid HIV testing of pregnant women in labour at the National Hospital Abuja to determine the HIV seroconversion rate in pregnancy and the prevalence of HIV in pregnant women in labour with previously unknown status. HIV testing and counseling (HTC) was acceptable to 224 (99.6%) of the pregnant women who met the study criteria. The mean 'turnaround' time for test result was 288 minutes and 16.2 minutes for tests performed in the hospital laboratory and those performed at the point-of-care (labour ward) respectively. HIV seroconversion was detected in 2(1.2%) of the 165 parturients with initial HIV negative result early in the index pregnancy. HIV infection was detected in four (2.7%) of the 59 parturients with unknown HIV status. Secondary school level education was significantly associated with HIV seroconversion in pregnancy P < 0.001. HTC in labour using rapid testing strategy is feasible and acceptable in our setting. The introduction of HCT will lead to the diagnosis of HIV positive women in labour, appropriate interventions and prevention of MTCT of HIV. PMID- 26897923 TI - Cash Transfers to Increase Antenatal Care Utilization in Kisoro, Uganda: A Pilot Study. AB - The World Health Organization recommends four antenatal visits for pregnant women in developing countries. Cash transfers have been used to incentivize participation in health services. We examined whether modest cash transfers for participation in antenatal care would increase antenatal care attendance and delivery in a health facility in Kisoro, Uganda. Twenty-three villages were randomized into four groups: 1) no cash; 2) 0.20 United States Dollars (USD) for each of four visits; 3) 0.40 USD for a single first trimester visit only; 4) 0.40 USD for each of four visits. Outcomes were three or more antenatal visits and delivery in a health facility. Chi-square, analysis of variance, and generalized estimating equation analyses were performed to detect differences in outcomes. Women in the 0.40 USD/visit group had higher odds of three or more antenatal visits than the control group (OR 1.70, 95% CI: 1.13-2.57). The odds of delivering in a health facility did not differ between groups. However, women with more antenatal visits had higher odds of delivering in a health facility (OR 1.21, 95% CI: 1.03-1.42). These findings are important in an area where maternal mortality is high, utilization of health services is low, and resources are scarce. PMID- 26897924 TI - Condom Tamponade in the Management of Primary Postpartum Haemorrhage: A Report of three cases in Ghana. AB - Postpartum haemorrhage is one of the major causes of maternal mortality worldwide. The leading cause of primary postpartum haemorrhage is uterine atony and active management of the third stage of labour with oxytocin is recommended for preventing primary postpartum haemorrhage. Parenteral oxytocin is also the drug of choice for medical management of postpartum haemorrhage secondary to uterine atony. Condom uterine balloon tamponade is .a low cost technique that can be used as a second-line option for treatment. We report retrospectively three cases of primary PPH secondary to uterine atony which were managed successfully with condom tamponade. Condom tamponade is effective in managing post partum haemorrhage secondary to uterine atony and we advocate for the training of all skilled attendants on how to insert the condom tamponade. PMID- 26897925 TI - [Application to Individual Identification of Parastic Virus Genotypes]. PMID- 26897926 TI - [Physicochemical and Biological Properties of Mineral Trioxide Aggregate as a Pulp Capping Material]. PMID- 26897927 TI - Anatomical Resection of the Bile Duct: A Hidden Door to the Bile Duct. AB - BACKGROUND/AIMS: Pancreas-preserving resection of the bile duct has been attempted as an organ preserving procedures for the treatment of low-grade malignant neoplasms of the bile duct. The fact that the lower bile duct penetrates pancreas head to join the duodenum, makes those attempts one of the challenging procedures in biliary tract surgery. Here we present a novel and unique surgical technique for anatomically resecting lower bile duct, focusing on the anatomy of the pancreas head. METHODOLOGY: A patient with middle bile duct cancer underwent this procedure. Subsequent to Kocher's maneuver, pancreas head was dissected from the posterior side of the duodenum that was a key step to recognize the embryological fusion plane between the anterior and the posterior pancreatic segments. Along this fusion plane pancreas head was able to be divided and the covering pancreatic parenchyma was split open to expose the whole intrapancreatic bile duct. RESULTS: The patient had no signs of pancreatic fistula and post-operative course was uneventful. Negative surgical margins were obtained thanks to the presented technique. CONCLUSIONS: This procedure might be applicable for the treatment of bile duct neoplasms, in case of lesions spread to the lower bile duct. Otherwise that might require pancreatoduodenectomy. PMID- 26897928 TI - Comparison Between Endoscopic Biliary Stenting and Nasobiliary Drainage in Patients with Acute Cholangitis due to Choledocholithiasis: Is Endoscopic Biliary Stenting Useful? AB - BACKGROUND/AIMS: To clarify whether or not use of an endoscopic biliary stenting (EBS) is superior to endoscopic nasobiliary drainage (ENBD) in cases of acute cholangitis due to choledocholithiasis. METHODOLOGY: Of 447 patients with choledocholithiasis who were treated in the Department of Gastroenterology, Fukuoka University Chikushi Hospital between January 1994 and September 2006, the subjects were 99 moderate acute cholangitis patients who underwent endoscopic drainage as initial treatment. Clinical efficacy, complications and patient satisfaction (meal intake rete) were investigated in the EBS group (67 patients) and the ENBD group (32 patients). RESULTS: There were no significant differences in the improvement in inflammation, total bilirubin, or biliary enzymes between the EBS and ENBD groups. Catheter occlusion was seen in three patients (4%) in the EBS group, and the catheter was self-extracted by three patients (10%) in the ENBD group. CONCLUSION: In moderate acute cholangitis due to choledocholithisis, the treatment efficacy and safety of EBS are equal to those of ENBD, and EBS appears to be a better choice in elderly patients in particular. PMID- 26897929 TI - Effects of Statin, Aspirin or Metformin Use on Recurrence-Free and Overall Survival in Patients with Biliary Tract Cancer. AB - BACKGROUND/AIMS: The impact of statins, aspirin and metformin use on recurrence free (RFS) and overall survival (OS) of patients with biliary tract cancer (BTC) has not been evaluated. METHODOLOGY: Baseline demographics/comorbidity and use of statins, aspirin or metformin at diagnosis were evaluated in patients with BTC from January/1987-July/2013. RESULTS: Median age at diagnosis; 65.7 years, performance status < 2; 795 patients, male; 461 (50.5%). Among 913 patients; 151 (16.5%) reported statin use at diagnosis, 146 (16%) aspirin use, and 81 (9%) metformin use. Charlson Comorbidity index score was not significantly associated with RFS or OS. Stage was prognostic on multivariable analysis for RFS and OS (both P <= 0.001) and age, performance status >= 2 and site were also prognostic for OS (P < 0.05, P < 0.001, and P < 0.05 respectively). Recurrence-free and OS among statin-users and nonusers was similar (RFS Hazard Ratio [HR]1.11, 95% confidence interval [CI] 0.78 - 1.58, P = 0.57), (OS HR0.98, 95% CI 0.77-1.24, P = 0.86), and among aspirin-users and nonusers (RFS HR0.83, 95% CI 0.57-1.23, P = 0.35), (OS HR1.07, 95% CI 0.85 - 1.34, P = 0.58), and among metformin-users and non-users (RFS HR0.75, 95% CI 0.43-1.30, P = 0.30), (OS HR0.96, 95% CI 0.69-1.33, P = 0.79). CONCLUSION: In this large retrospective cohort of BTC patients, comorbidity, statin, aspirin or metformin use did not have significant effects on RFS or OS. PMID- 26897930 TI - One-Step LC and ERCP Treatment of 40 Cases with Cholelithiasis Complicated with Common Bile Duct Stones. AB - BACKGROUND/AIMS: To discuss the clinical significance of combined application of laparoscopic cholecystectomy (LC) and endoscopic retrograde cholangiopancreatography (ERCP) for one-stage treatment of cholelithiasis complicated with common bile duct stones. METHODOLOGY: To retrospectively analyze 40 cases with cholelithiasis complicated with common bile duct stones treated with LC plus intraoperative ERCP between May 2005 and September 2012 and to evaluate the clinical efficacy in the treatment of cholelithiasis complicated with common bile duct stones. RESULTS: Among 40 cases, 36 successfully underwent LC plus intraoperative ERCP and 4 were transferred to open surgery. Eighteen patients with preoperative abnormal liver function showed declined indexes post operatively. Compared with LC, more patients had abdominal distention and vomiting. Seven patients presented with transient increase in the levels of serum amylase with no incidence of acute pancreatitis. One had hematochezia and recovered after conservative treatment with no incidence of bile leakage and perforation and other severe complications. CONCLUSIONS: LC combined with intraoperative ERCP is safe and efficacious in the primary treatment of cholelithiasis complicated with common bile duct stones to avoid open surgery and double surgeries. PMID- 26897931 TI - Short-Term Surgical Outcomes and Experience with 925 Patients Undergoing Robotic Cholecystectomy During A 4-Year Period At A Single Institution. AB - BACKGROUND/AIMS: Robotic cholecystectomy has emerged as an established technique for the treatment of gallbladder disease. We report our experience and surgical results of RC for patients with gallbladder polyps or minimal symptomatic gallstones, and with inflamed gallbladder diseases including acute cholecystitis, empyematous cholecystitis, and gangrenous cholecystitis. METHODOLOGY: 925 patients with gallbladder disease were selected to undergo RC at our institution. All procedures were performed using the da Vinci system. No technical difficulty in RC was experienced. Use these advantages, we performed cholecystectomy by placing the trocars transversally on the bikini line('Panty line', 'Bikini line'). RESULTS: From June 2010 to May 2014, 925 gallbladder disease patients underwent RC on the bikini line. Excluding the effects of BMI produced no correlation between operating time and white blood cell count (r = 0.062, p = 0.058). Surgical complications occurred in nine of the 925 patients (0.1%), including cystic duct leakage (n = 4), bleeding (n = 3), common bile duct injury (n = 1), and bladder injury (n = 1). Conversion to open cholecystectomy occurred in one patient due to common bile duct injury (0.01%). CONCLUSION: RC is technically an easy to learn, safe method of patients with gallbladder disease, regardless of BMI. In addition, RC can be a treatment for patients with acute inflammation in gallbladder disease. PMID- 26897932 TI - Clinical Application of Six Current Classification Systems for Iatrogenic Bile Duct Injuries after Cholecystectomy. AB - BACKGROUND/AIMS: Due to being a severe complication, iatrogenic bile duct injury is still a challenging issue for surgeons in gallbladder surgery. However, a commonly accepted classification describing the type of injury has not been available yet. This study aims to evaluate ability of six current classification systems to discriminate bile duct injury patterns. METHODOLOGY: Twelve patients, who were referred to our clinic because of iatrogenic bile duct injury after laparoscopic cholecystectomy were reviewed retrospectively. We described type of injury for each patient according to current six different classifications. RESULTS: 9 patients underwent definitive biliary reconstruction. Bismuth, Strasberg-Bismuth, Stewart-Way and Neuhaus classifications do not consider vascular involvement, Siewert system does, but only for the tangential lesions without structural loss of duct and lesion with a structural defect of hepatic or common bile duct. Siewert, Neuhaus and Stewart-Way systems do not discriminate between lesions at or above bifurcation of the hepatic duct. CONCLUSION: The Hannover classification may resolve the missing aspects of other systems by describing additional vascular involvement and location of the lesion at or above bifurcation. PMID- 26897933 TI - Mystery Story about Erythropoietin (Epo) and Erythropoietin Receptor (EpoR) are Disguised? AB - In this review we would like to focus our attention upon very controversial reports on Erythropoietin (Epo) and Erythropoietin Receptor (EpoR) expression in cancer patients. The effects of Epo on cancerous tissues are poorly understood. Hypoxia results in an increase in the level of the production of both Epo and EpoR via activation of the hypoxia-inducible factor 1 (HIF-1) pathway. HIF 1alpha, promotes the expression of vascular endothelial growth factor (VEGF). The signaling through VEGF in both a paracrine and an autocrine manner is required for the homeostasis of adult vessels. Macrophages stimulate vessel sprouting via a soluble factor other than VEGF, rather than through direct contact with endothelial cells. The intriguing questions are set about many researches to link Epo/EpoR expression and function in order to establish one of the mechanisms of tumor growth, disease progression of cancer patient. However, it is uncertain role in tumour angiogenesis as promoter and stimulator of tumour growth which should need to be furtherly validated. PMID- 26897934 TI - Perioperative Outcomes after Pancreaticoduodenectomy in Elderly Patients. AB - BACKGROUND/AIMS: Pancreaticoduodenectomy (PD) is highly invasive and may be associated with critical to fatal complications. The purpose of this study is to demonstrate, using multivariate analysis of preoperative and intraoperative patient characteristics to determine risk factors for negative outcomes, that PD can be performed safely in the elderly. METHODOLOGY: We enrolled 108 patients who underwent PD between October 2007 and December 2014. We compared perioperative outcomes such as the incidence of post-operative complications, duration of hospital stay, and mortality between elderly (group A; age >= 75 years, n = 44) and younger (group B; age < 75 years, n = 64) groups. RESULTS: Death occurred in one patient (2.3%) in group A. There were no significant differences between the groups in rates of major complications, including pancreatic fistula (PF), delayed gastric emptying, intra-abdominal bleeding, pneumonia, or duration of hospital stay. Multivariate analysis revealed complications in elderly to be associated with hemoglobin concentration (P = 0.016), and PF to be associated with body mass index (P = 0.013) and soft pancreas (P = 0.005). CONCLUSIONS: PD can be performed safely in elderly patients aged >= 75 years. However, PD indication for elderly having low hemoglobin concentration patients should be carefully selected. PMID- 26897935 TI - Evaluation of the Response to Chemotherapy in Advanced Gastric Cancer by Contrast Enhanced Harmonic EUS. AB - BACKGROUND/AIMS: In advanced gastric cancers, a significant correlation exists between the response to chemotherapy in primary gastric cancers and patient prognosis. Therefore, accurate evaluation of the response to chemotherapy in primary gastric cancers is important. We examined the response to chemotherapy in primary gastric cancers by contrast-enhanced harmonic endoscopic ultrasonography (CEH-EUS). METHODOLOGY: Thirty-five patients with advanced gastric cancer underwent CEH-EUS. Among these patients, 19 patients with stage IV advanced gastric cancer who received chemotherapy and CEH-EUS more than twice were enrolled, and evaluated the response to chemotherapy in primary gastric cancers by CEH-EUS and endoscopy. RESULTS: In PRs evaluated by endoscopic findings, echo intensity ratio (EIR) was decreased, and in PDs EIR was increased significantly by CEH-EUS. Five cases had difficulty in evaluating the response of primary gastric cancers to chemotherapy by endoscopy, while evaluation was possible in those 5 cases by CEH-EUS. CONCLUSIONS: CEH-EUS is a new method to evaluate responses to chemotherapy in primary gastric cancers not only by a change in size but also in tumor vascularity. Correct evaluation of primary gastric cancers by CEH-EUS help predicting prognosis of patients. PMID- 26897936 TI - Clinicopathological Features of Second Primary Colorectal Cancer Incidentally Identified by 18F-FDG-PET. AB - As positron emission tomography using F18-fluorodeoxyglucose (FDG-PET) is becoming a common imaging modality the number of colorectal cancers incidentally detected by FDG-PET is expected to increase. In this study, we investigated the clinicopathological features of 15 cases of second primary colorectal cancer incidentally detected by PET during other cancer evaluation in patients who underwent surgery. We also discussed the significance of FDG-PET in evaluating cancer status. None of the patients had undergone FDG-PET for suspected colorectal disease; 6 were being evaluated by FDG-PET for lung cancer, 5 for nasopharyngeal or laryngeal cancer, 3 for gastrointestinal cancer, and 1 for uterine cancer. The average tumor size was 36.1 +/- 14.4 mm (range, 25-70 mm) and the mean maximum standardized uptake value (SUVmax) was 11.9 +/- 6.0 (range, 3.0 29.6). Although 4 cases (26.7%) had distant metastasis, 3 (20%) were Tis or T1 cancer, 3 (20%) were T2 cancer. Of the 15 cases, 6 (40%) could have been underwent laparoscopic surgery. Our study found that asymptomatic cases of colorectal cancer can be detected by FDG-PET during evaluation for other cancer. Therefore, in some cases, FDG-PET is useful for detecting second primary colorectal cancer at a relatively early and curable stage. PMID- 26897937 TI - Outlet Obstruction of Temporary Loop Diverting Ileostomy. AB - Stoma formation is commonly performed in operations to treat carcinoma, inflammatory bowel disease (IBD) and familial adenomatous polyposis (FAP). In this study, we report several cases of stomal outlet obstruction and investigate the clinical features of cases of outlet obstruction in patients who underwent diverting loop ileostomy. Sixty-one patients with IBD, FAP or rectal cancer who required diverting loop ileostomy were identified for inclusion in this study. We defined outlet obstruction as a small bowel obstruction at the opening of the ileostomy following surgery. All cases of outlet obstruction were diagnosed by computed tomography. In the univariate analysis the type of diagnosis, type of operation, age, and white blood cell count were the factors significantly associated with outlet obstruction following ileostomy, and outlet obstruction was considered to have a connection with restorative proctocolectomy. In conclusion, we found that adhesion and twisting of the ileostomy were the causes of outlet obstruction. For temporary diversion, simple rotation of the ileostomy should be recommended, especially in restorative proctocolectomy. Additional study is required to explore other risk factors of outlet obstruction. PMID- 26897938 TI - Totally Curative Surgical Resection of Retrorectal Tumors. AB - BACKGROUND/AIMS: Retrorectal (also known as presacral) tumor (RT) is a rare disease of retrorectal space. There is no large numbered case series in the literature. Well documented small numbered case series will help to establish meta-analysis and surgical decision making. METHODOLOGY: Between 2000 and 2014 medical records of patients with diagnosis of RT at two institutions were reviewed. Clinical features, diagnostic studies, type of surgery, surgical findings, surgical technique, and histopathology of the tumor, morbidity and survival are examined based on data registry. RESULTS: During 14 years period of time, total of 12 patients operated with diagnosis of RT were retrieved to this study. There were five men and seven women. The median age at the time of diagnosis was 43 (27-56) years. The most frequent findings were pain and palpable mass. There were five anterior, four posterior and three anteroposterior approaches for surgery. There is no recurrence or disease related mortality observed after median of 7 years (1-14). CONCLUSION: The primary and only satisfactory treatment is surgery for RTs. Prognosis is directly related primary local control with complete excision, which is often difficult to achieve for malignant lesions. PMID- 26897939 TI - Hepatic Arterial Infusion Chemotherapy for Life Threatening Patients due to Liver Metastases from Colorectal Cancer with Cetuximab. AB - BACKGROUND/AIMS: This retrospective report evaluated the safety and efficacy of hepatic arterial infusion chemotherapy (HAIC) for life threatening patients with unresectable hepatic metastases. METHODOLOGY: Seven life threatening patients with hepatic metastases who were treated with HAIC up to September 2011 were retrospectively analyzed. As HAIC regimen, 5-FU (1000mg/m2) was administered weekly via continuous 5-hour infusion using a continuous-infusion device. After improvement of liver dysfunction, cetuximab was administered simultaneously by the same dose of single administration. Treatment was repeated weekly until progression of hepatic lesion or discontinuity by unacceptable toxicity or patients' proposal. RESULTS: In 5 patients with hepatic metastasis related complaints, 3 patients improved after the initiation of HAIC. Three out of 4 patients with PS 2 or 3 were improved by the initiation of HAIC. The median OS was 9.5 months. No severe adverse toxicities and no treatment death related to HAIC were observed. The most severe non-hematologic adverse events were ALP in 3 patients, transaminase and bilirubin in 1 patient with grade 3. CONCLUSION: HAIC may be considered to perform when the hepatic metastases progress as life threatening status even though those are refractory to standard systemic chemotherapy. PMID- 26897940 TI - Decreased Expression of MIR-134 and its Clinical Significance in Human Colorectal Cancer. AB - BACKGROUND/AIMS: Dysregulation of miRNA is always associated with cancer development and progression. Aberrant expression of miR-134 has been found in some types of cancer. However, miR-134 expression and its clinical significance in colorectal cancer (CRC) have not been explored. The aim of this study was to explore the effects of miR-134 in CRC tumorigenesis and development. METHODOLOGY: Quantitative RT-PCR was performed to evaluate miR-134 levels in CRC cell lines and 168 pairs of CRC specimens and adjacent noncancerous tissues. The association of miR-134 expression with clinicopathological factors and prognosis was also analyzed. Further, the effects of miR-134 on the biological behavior of CRC cells were investigated. RESULTS: MiR-134 expression was significantly downregulated in CRC cancer tissues and cell lines. Decreased miR-134 expression was significantly associated with large tumor size, positive lymph node metastasis, and advanced clinical stage Low miR-134 expression in CRC was an independent predictor of poor survival. Moreover, over-expression of miR-134 inhibited SW620 cell proliferation, invasion, and migration, and promoted cell apoptosis in vitro. CONCLUSIONS: These findings indicate that miR 134 may act as a tumor suppressor in CRC and would serve as a novel therapeutic agent for miR-based therapy. PMID- 26897941 TI - Clinical Characteristics of Ischemic Colitis in Elderly Patients. AB - BACKGROUND/AIMS: The aim of this study was to retrospectively analyze the endoscopy findings, clinical symptoms, signs and biochemical data of elderly patients with ischemic colitis (IC). METHODOLOGy: A retrospective study of 58 patients diagnosed with IC in the endoscopy center of Jinan Central Hospital from October 2008 to October 2013 was carried out. The patients were divided into two groups based on the age: elderly group (>= 65 years) versus young group (< 65 years). Symptoms, signs, biochemical data, endoscopic findings and the length of hospitalization were compared. RESULTS: Of the 58 patients with IC (43 women and 15 men), the median age was 72.5 years (range 30-84 years), and 70.69% (41/58) were over the age of 65 years. Compared with the young group, the elderly group had a less frequent hyperactive bowel sounds, a higher baseline levels of C reactive protein(CRP) and a longer average periods of hospitalization. CONCLUSION: Clinical characteristics of IC in the elderly were similar to those in the young group. CRP may be involved in the development of IC in the elderly patients. By considering the basic dieases combined with CRP levels, it is possible to more effectively predict and prevent the development of IC. PMID- 26897942 TI - The Significance of Combined Measurement of p53 Antibody and other Tumor Markers for Colorectal Cancer after Curative Resection. AB - BACKGROUND/AIMS: Though serum p53 antibody has been widely used, it is mentioned that it is not related to clinical parameters of colorectal cancer (CRC) and has no prognostic significance in long-term follow-up. The aim of this study was to explore the possibility to increase the value of p53 antibody in combination with carcinoembryonic antigen (CEA) and CA19-9 for post operation follow up. METHODOLOGY: One hundred twenty-eight patients with primary CRC who underwent surgery were enrolled in this study. Serum p53 antibodies, CEA and CA19-9 were measured before and after the surgery and their impact on CRC staging patient survival. DNA was extracted from colorectal cancer tissue and KRAS mutation analysis was determined by direct sequencing. RESULTS: Thirty seven point five patients were positive for serum p53 antibodies before the operation. Total 67.2% patients were positive with any tumor markers, but it was only 3.9% that were positive with all markers. There was no association between KRAS mutation and p53 antibody level. CONCLUSIONS: The combined use of tumor markers can be an effective screening method for detection of colorectal cancer. If serum p53 antibody level continues to be positive for long after resection, the case should require subsequent intense follow-up. PMID- 26897943 TI - Pure Robotic Surgery for Intraluminally Growing Gastrointestinal Stromal Tumors around the Esophagogastric junction or Pyloric Ring. AB - BACKGROUND/AIMS: Laparoscopic resection of gastrointestinal stromal tumors has become wide-spread as a minimally invasive surgical method. However, the limitations of laparoscopic surgery for GISTs are well recognized. METHODOLOGY: We developed a local resection by pure robotic surgical procedure to treat intraluminally growing GISTs located in sites that are unsuitable for laparoscopic surgery. Using articulated robotic arms, the GIST is completely excised with a safe margin while employing a unique technique to provide a good operative view and to prevent the intra-abdominal dissemination of the tumor from the cut edge created by robotic excision. The defect created after excision of the tumor is closed using robotic sewing. RESULTS: Four patients were successfully treated with pure robotic surgery without conversion to laparoscopic or open surgery or changing in the method of gastrectomy. CONCLUSIONS: Using robotic surgery, intraluminally growing GISTs located in sites unsuitable for conventional laparoscopic surgery can be treated with minimally invasive procedures. PMID- 26897944 TI - Characteristics of Emergency Gastrointestinal Stromal Tumor (GIST). AB - BACKGROUND/AIMS: Gastrointestinal Stromal Tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract (GIT). Importance of GISTs is increasing while surgeons are facing with more frequent either in emergency setting of elective cases. Delineating the presentation and management of emergency GIST is important. METHODOLOGY: From 2005 to 2014, emergency cases with final diagnosis of GIST were examined retrospectively. Total of 13 operated cases were evaluated by patients characteristics, clinical presentation, operational findings and postoperative prognosis. RESULTS: There were 9 male and 4 female with the mean age of 48.15 years. The most frequent presentations are ileus and GIT hemorrhage both covering the 84% of patients. Small bowel was the dominating site with ileus. Stomach was the second frequent site of the disease with the finding of hemorrhage. CONCLUSION: Emergency patients are more likely to come with small bowel GIST and obstruction symptoms. Hemorrhage is the most frequent symptom for emergency GIST of stomach and duodenum. PMID- 26897945 TI - Diagnosis and Treatment of Duodenal Injury: A Clinical Analysis. AB - BACKGROUND/AIMS: Duodenal injuries do not often occur and are usually difficult to be diagnosed or treated. METHODOLOGY: To summarize the experience in managing duodenal injuries and determine some prognostic factors, we conducted a retrospective review on 42 cases of duodenal injuries including 17 traumatic (blunt 31.0%, penetrating 9.5%) and 25 iatrogenic (59.5%) ones, which were admitted to our hospital from 1993 to 2013. RESULTS: The mortality rate was 23.8% (n = 10). Main cause of late death was multiple system organ failure and infection. Senility and high APACHE II score were both correlated with mortality rate (P < 0.01 and P < 0.05 respectively). High morbidity and mortality rate were more likely to be associated with those had long delays in treatment or injury in the second part of the duodenum (P < 0.05). The number of associated injuries affected mortality rate (P < 0.05). For traumatic injuries, the mechanism of injury, method of initial surgical management, Organ Injury Scale and Abbreviated Injury Scale were not related to patients' outcome (P > 0.05). CONCLUSIONS: These findings indicated that early diagnosis and timely treatment were of great clinical value. Primary repair with an effective diversion was practicable. Age and APACHE II Score were the independent prognostic factors. PMID- 26897946 TI - Safety and Efficacy of Anti-TNFalpha Treatment in Crohn's Disease Patients with Abdominal Abscesses. AB - BACKGROUND/AIMS: It is estimated that up to 30% of CD patients develop abdominal abscesses; the management of active luminal CD in such patients represents a clinical challenge. The aim of this study is to assess the safety of biologics in patients with Crohn's disease and abdominal abscesses treated with percutaneous drainage and/or broad-spectrum antibiotics. METHODOLOGY: We performed a retrospective review of the clinical charts of consecutive Crohn's disease patients with abdominal abscesses treated with anti-TNFalpha therapy attended in our institution. RESULTS: 12 patients were finally included in the study. All were treated with broad-spectrum antibiotic and biological therapy (anti-TNF); indication of anti-TNFalpha therapy was moderate to severe activity of CD in all of them. Percutaneous drainage of the abscess was performed in 7 of the 12 patients. No complications were observed during a mean follow-up of 37,8 (16-71) months, including abscess volume increase, enterocutaneous fistula, soft tissue infections, bacteraemia, or need for emergency surgery. CONCLUSIONS: In addition to conventional treatment, the use of anti-TNFalpha therapy in Crohn's disease patients with abdominal abscesses seems to be safe. Usefulness of this approach has to be validated in larger cohorts. PMID- 26897947 TI - Serum Type IV Collagen Concentration Correlates with Indocyanine Green Retention Rate and is an Indicator Of Hepatotoxicity In Patients Receiving FOLFOX for Colorectal Cancer. AB - BACKGROUND: Assessment of oxaliplatin-associated hepatotoxicity in patients receiving oxaliplatin, fluorouracil and leucovorin chemotherapy (FOLFOX) for colorectal cancer remains controversial. The aims of this study were to clarify which variables are indicators of such hepatotoxicity. METHODOLOGY: Twenty-seven patients who were to receive FOLFOX for colorectal cancer were included in this study. A range of liver function tests, including serum hyaluronic acid (HA) and type IV collagen concentrations, indocyanine green (ICG) retention rate at 15 min (ICGR15) and splenic volume were assessed before commencement of chemotherapy and after four cycles of FOLFOX. RESULTS: No significant changes were found in conventional liver function tests or splenic volume. Significant changes pre- and post-FOLFOX were found in type IV collagen concentrations and ICGR15. Correlation analyses showed that the following two factors were associated with significant changes in ICGR15 after four cycles of FOLFOX: platelet count (p = 0.028, correlation coefficient 0.423), and type IV collagen concentration (p < 0.001, correlation coefficient 0.830). The regression line between type IV collagen concentration and ICGR15 was Y = 2.70 + 0.84 x X. CONCLUSION: Serum type IV collagen concentration is an indicator of oxaliplatin-associated hepatotoxicity and correlates with significant changes in ICGR15 in patients receiving FOLFOX. PMID- 26897948 TI - Hepatic Manifestations in Wilson's Disease: Report of 110 Cases. AB - BACKGROUND/AIMS: Wilson's disease is a rare disease and difficult to establish diagnosis. We aim to improve understanding and early diagnosis. METHODOLOGY: Medical records were reviewed for 110 patients with Wilson's disease. The clinical manifestations and laboratory findings were retrospectively analyzed, especially in terms of age, type of liver injury. RESULTS: Age range at diagnosis was wide (4 to 52 years).The most frequent hepatic manifestations observed were jaundice (40.9%), fatigue (37.3%), nausea or vomiting (32.7%) and bloating (30.0%). Hepatic involvement in affected patients may take one of several different presentations. Thirty-eight patients were found cirrhosis with asymptomatic or slowly progressive hepatic dysfunction. Twelve were acute liver failure superimposed on chronic cirrhosis. Fifteen were acute hepatic failure without cirrhosis. Nineteen presented as acute hepatitis. Four showed chronic liver dysfunction. Five were asymptomatic aminotransferasemia. Another 17 patients showed neurological disorders with cirrhosis. Kayser-Fleischer rings were found in 91.3% patients. The serum ceruloplasmin decreased in 85.1%, 24-hour urinary copper increased in 83.9%, and serum copper decreased in 61.9% patients. CONCLUSIONS: The clinical manifestation of Wilson's disease is very diverse and no one feature is completely reliable. Patients at any age with liver injury of unknown etiology should be screened for Wilson's disease. PMID- 26897949 TI - Planning Sonography Using Real-time Virtual Sonography and Contrast-enhanced Sonography for Radiofrequency Ablation of Inconspicuous Hepatocellular Carcinoma Nodules. AB - BACKGROUND/AIMS: Determining whether planning sonography, using real-time virtual sonography (RVS) and contrast-enhanced sonography (CEUS), enables the identification of inconspicuous HCC nodules on conventional sonography (US), during percutaneous radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). METHODOLOGY: We examined the factors associated with poor conspicuity, identification rate of inconspicuous HCC nodules in planning US using RVS and CEUS, the success rate of RFA for such nodules and local recurrence rates. RESULTS: Sixty inconspicuous HCC nodules were analyzed. Factors associated with poor conspicuity included location of the nodules for 34 nodules, US findings of HCC nodules for 24 nodules, US findings of surrounding hepatic parenchyma for 26 nodules and local recurrence for 18 nodules. Fifty-five (90.0%) HCC nodules were identified with RVS. Of the remaining five HCC nodules, three were visualized with CEUS. Thus, 96.7% (58/60) of the inconspicuous HCC nodules were identified. Forty-six (79.3%) identified HCC nodules, were treated with RFA; the success rate was 95.7% (44/46). The cumulative local recurrence rates were 0%, 2.7% and 9.4% at 12, 24 and 36 months, respectively. CONCLUSIONS: This study suggested that planning US using RVS and CEUS permits the identification of most inconspicuous HCC nodules, thereby improving the success rate of RFA. PMID- 26897950 TI - The Transmediastinal, Intrapericardial Inferior Vena Cava Approach for Hepatectomy of a Large Liver Tumor Invading the Hepatic Vein Confluence. AB - We report the case of a large multilocular upper liver tumor invading the hepatic vein confluence in a 41-year-old male, and the safe resection of the tumor using a transmediastinal, intrapericardial inferior vena cava (IVC) approach. Several methods for exposing suprahepatic IVCs on the cranial side of the diaphragm have been reported. However, the approach to supradiaphragmatic IVCs varies, and there are currently no reports that provide a detailed description of the anatomical landmarks during the intrapericardial IVC approach. In the case reported herein, anatomic landmarks, including the prepericardial fat in the pericardial trigone, were confirmed during the transmediastinal, intrapericardial IVC approach. We believe that such anatomic landmarks are important to ensure a safe approach to the pericardium and the intrapericardial IVC through the anterior mediastinum. We think this case report is useful in elucidating the resection of large liver tumors invading the hepatic vein confluence. PMID- 26897951 TI - Acoustic Radiation Force Impulse (ARFI) for Fibrosis Staging in Patients with Autoimmune Hepatitis. AB - BACKGROUND/AIMS: The performance of non-invasive fibrosis markers has not been well studied in autoimmune hepatitis (AIH). Acoustic radiation force impulse imaging (ARFI) is a non-invasive radiological method for assessment of liver fibrosis. The aim of this study was to evaluate the accuracy of ARFI for fibrosis staging in patients with AIH. METHODOLOGY: AIH patients who undergone for control liver biopsy after at least two years of biochemical remission period were also assessed by ARFI. Liver fibrosis was staged according to the METAVIR scoring system. RESULTS: A total of 15 patients (13 women and 2 men) with mean age of 40.9 (18-59 years) were included in the study. Repeat liver biopsy was performed a mean of 4.9 (3-9 years) after AIH diagnosis. Nine patients had significant fibrosis scores (F >= 2) while, remain 6 patients had mild or no fibrosis. The mean (+/-SD) shear wave velocities for patients with fibrosis stage II-IV was significantly higher than those with fibrosis stage 0-I (2.28 +/- 0.68 m/s and 1.20 +/- 0.24, respectively, p = 0.002). CONCLUSIONS: ARFI is able to differentiate significant from non significant liver fibrosis in patients with AIH. Our study suggests that this non-invasive method can be used for monitoring fibrosis progression in AIH. PMID- 26897952 TI - Technique of Transbrachial Angiography and Treatment for Abdominal Diseases: A Study of 6262 Patients. AB - For over 20 years, we have been using the transbrachial approach as the first line option for abdominal angiography and transcatheter arterial chemoembolization (TACE). The present study involving 6262 patients (success rate of 99.8%) showed that the transbrachial approach could be used for superselective angiography or computed tomography during angiography (angio-CT) and was effective for hemostasis of abdominal aneurysmal hemorrhage, diverticular hemorrhage and partial splenic embolization. The approach was highly safe with no association with serious complications. Bleeding from the puncture site was reported in 225 cases (0.36%), numbness due to nerve damage at the puncture site. was reported in 376 cases (0.6%), and arteriovenous fistula in the puncture site was reported in 84 cases (0.13%). In the treatment of hepatic disease, the guiding catheter could be inserted deeper into the hepatic artery, and hemostasis after sheath removal required shorter time compared with the transfemoral approach. Based on its safety and usefulness, transbrachial angiography and intervention therapy is a first-line treatment for abdominal diseases. PMID- 26897953 TI - Clinical Features of Surgical Resection for Liver Metastasis from Extremity Soft Tissue Sarcoma. AB - BACKGROUND/AIMS: The aim of the present study was to define the prognostic factors for survival after hepatic metastasectomy from extremity soft tissue sarcoma. METHODOLOGY: Between January 2000 and January 2009, 27 patients with hepatic metastases from extremity soft tissue sarcomas underwent liver resection with radical intent. Various clinicopathologic variables were investigated retrospectively to identify possible prognostic factors for survival after hepatic metastasectomy. RESULTS: Overall survival was 46% and 24% at 5 and 10 years after liver resection, respectively. Disease-free survival was 13% at 1 year after hepatic metastasectomy. On multivariate analysis, disease-free interval longer than 24 months (P = 0.010), no tumor recurrence before hepatic metastasectomy (P = 0.040) and negative margin resection (P = 0.002) provided a significantly favorable overall survival. Repeated hepatic metastasectomy for recurrent hepatic metastases (P = 0.007) also provided a favorable overall survival. CONCLUSION: Hepatic metastasectomy for extremity soft tissue sarcoma can be associated with prolonged survival. Complete resection, longer disease free interval, no tumor recurrence before liver resection and repeated resection for recurrent liver metastases are the most predictive factors for prolonged survival. PMID- 26897954 TI - Utility of Partial Splenic Embolization for Hypersplenism using Guglielmi Detachable Coils. AB - BACKGROUND/AIMS: We examined the utility of partial splenic embolization (PSE) using a Guglielmi Detachable Coil (GDC) comparing its safety and therapeutic efficacy with those of conventional metallic coils (IDC). METHODOLOGY: The GDC group comprised 8 patients who were subjected to embolization using a GDC in combination with an IDC, and the IDC group comprised 13 patients. Treatment factors were evaluated by the total number of coils used. We assessed the mean C reactive protein (CRP) and the increased rate of platelet counts, 2 weeks after treatment. RESULTS: The rate of increase in platelet counts at 2 weeks after PSE was 2.47 in the GDC group and 3.18 in the IDC group (p = 0.076). The mean CRP levels were 3.0 in the GDC group and 5.9 in the IDC group (p = 0.14). The mean number of coils were 5.3 in the GDC group and 15.3 in the IDC group and this difference was statistically significant (p = 0.0008). CONCLUSION: A GDC is excellent in terms of stability and allows the operator to conduct embolization of hypersplenism in an accurate and reliable manner. In summary, use of a GDC for hypersplenism reduced the total number of coils required for successful treatment. PMID- 26897955 TI - Long-Term Outcomes Of Surgical Resection for Liver Metastasis from Breast Cancer. AB - BACKGROUND/AIMS: The aim of the present study was to define the prognostic factors for survival after hepatic metastasectomy from breast cancer. METHODOLOGY: Between October 2003 and December 2013, 28 patients with hepatic metastases from breast cancer underwent liver resection with curative intent. All patients had obtained locoregional control of their primary breast tumors. Various perioperative variables were investigated retrospectively to confirm the role of pulmonary metastasectomy and to identify possible prognostic factors for survival after hepatic metastasectomy. RESULTS: Overall survival after liver resection was 53% and 23% at 5 and 10 years, respectively. Disease-free survival after hepatic metastasectomy was 20% and 0% at 5 and 10 years. On multivariate analysis, disease-free interval longer than 36 months (P = 0.003), no tumor recurrence before hepatic metastasectomy (P = 0.020) and complete resection (P = 0.008) provided a significantly favorable overall survival. CONCLUSION: Hepatic metastasectomy for breast cancer can be associated with prolonged survival. Complete resection, longer disease-free interval and no tumor recurrence before liver resection are the most predictive factors for prolonged survival. However, the accumulation of more cases is necessary to evaluate the prognostic factors properly and to determine the selection criteria for liver resection. PMID- 26897956 TI - Stroke Volume Variation for the Evaluation of Circulating Blood Volume after Living Donor Liver Transplantation. AB - BACKGROUND/AIMS: Stroke volume variation (SVV) is a sensitive, functional preload index for evaluating responsiveness to volume loading in patients during liver transplantation (LT). However, there have been few reports concerning the experience of using SVV after LT. METHODOLOGY: Of 61 patients who underwent living donor LT (LDLT) at our institute, we used only central venous pressure (CVP) to guide fluid management in the first 52 patients (conventional group) and used both SVV and CVP in the next 9 patients (SVV group). The boundary values used for fluid management were 10mmHg for CVP and 10% for SVV. Changes in SVV and CVP were compared. RESULTS: In the SVV group, SVV was less than 10% in all patients when the diuretic phase appeared. However, CVP was more than 10mmHg in only 4 cases (44.4%). Between surgery and the removal of endotracheal tubes, the lowest the ratio between arterial oxygen tension and fractional inspired oxygen (PaO2/FiO2 ratio) in the SVV group (290.7 +/- 100.5) was significantly higher than that in the conventional group (205.6 +/- 98.9, P = 0.017). CONCLUSION: Postoperative fluid management using SVV may be especially useful after LDLT. Monitoring the circulating blood volume using a 10% SVV index is useful for avoiding lung edema after LT. PMID- 26897957 TI - "Single Oval Ostium Technique" using Polytetrafluoroethylene Graft for Outflow Reconstruction in Right Liver Grafts with venous Anomalies in Living Donor Liver Transplantation. AB - Right lobe living donor liver transplantation form a major source of liver allografts in Asia because of the scarcity of deceased donation. However, the transplant surgeons often face challenges while managing right lobe liver allografts due to variations in vascular anatomy. Such variations have led the transplant team to adopt modifications in existing techniques of inflow and outflow reconstruction. One of such variations is presence of multiple draining inferior right hepatic veins (IRHVs). This hepatic venous anomaly pose a lot of technical difficulties in the outflow reconstruction as second and/or third anastomosis to inferior vena cava is not always possible in limited retrohepatic space. Herein, we describe the "Single oval ostium technique" using dual synthetic vascular grafts ensuring a common outflow channel for all the hepatic veins. PMID- 26897958 TI - Curative Analysis of Several Therapeutic Methods for Primary Hepatocellular Carcinoma with Portal Vein Tumor Thrombus. AB - BACKGROUND/AIMS: To evaluate the efficacy of different therapeutic methods for finding a promising treatment to this satanic disease and determined the prognostic factors affecting the survival time. METHODOLOGY: A retrospective study was carried out on 589 patients who underwent different treatment for Primary hepatocellular carcinoma with portal vein tumor thrombus from January, 2005 to June, 2013. Patients were divided into 4 groups according to the initial treatment: Group A (N = 48), conservative treatment; Group B (N = 86), chemotherapy; Group C (N = 122), surgical resection; and Group D (N = 333), surgical resection with postoperative chemotherapy. RESULTS: There was no significant differences in clinical information (i.e., the number of tumor, the size of tumor, and the state of portal vein tumor thrombus) among the 4 groups (P > 0.05). Both surgical resection and chemotherapy can improve the survival rate of the patients, and comprehensive treatments are of greater effect over surgical resection or chemotherapy alone. Univariate and multiple analyses revealed that the levers of AFP(p=.001), the size of tumor (p < .001), the number of tumor(p < .001), the state of portal vein tumor thrombus(p < .001), and the number of chemotherapy(p = .000) affected the conditions of prognosis: CONCLUSIONS: Positive operation treatment is the most effective therapeutic strategy for this advanced disease. Surgical resection followed by postoperative chemotherapy would increase the survival rate. PMID- 26897959 TI - Combination of Transarterial Chemoembolization (TACE) and Radiofrequency Ablation (RFA) vs. Surgical Resection (SR) on Survival Outcome of Early Hepatocellular Carcinoma: A Meta-Analysis. AB - Although TACE-RFA combination presented synergetic effect over monotherapy in patients with early HCC, whether it can achieve comparable survival outcome as surgical resection is still not clear. This study tried to pool previous studies to assess the survival outcome of TACE-RFA versus SR alone in early HCC patients with resectable small tumor. Four retrospective studies were included in this study. Pooled analysis showed that TACE-RFA provides comparable one and three year three overall survival (OS) rate and one year recurrence free survival (RFS) rate to surgical resection (SR) in the patients. However, this combination is associated with significantly lower three year RFS rate compared with SR. As to surgical complications, TACE-RFA group had significantly lower risk of major complications. Therefore, SR should still be considered as the primary choice for early HCC patients. But surgical complications should also be considered when deciding surgical procedures. Future large RCTs are required to confirm the findings of this study. PMID- 26897960 TI - Toward Curative Fluorescence-Guided Surgery of Pancreatic Cancer. AB - BACKGROUND/AIMS: Negative surgical margins are critical to prevent recurrence in cancer surgery. We review the use of fluorophore-labeled monoclonal antibodies to aid in cancer visualization in orthotopic nude mouse models of human pancreatic cancer in order to achieve negative margins in fluorescence-guided surgery (FGS). METHODOLOGY: Anti-CEA or anti-CA 19-9 antibodies were conjugated with fluorophores of visible and near-infrared wavelengths. Orthotopic primary and metastatic human pancreatic tumors in nude mouse models were readily visualized with fluorescence imaging after administration of fluorophore conjugated anti-CEA or anti-CA 19-9. RESULTS: The fluorescence signal was detectable 30 minutes after systemic antibody delivery and remained present for two weeks, with minimal in vivo photobleaching after exposure to standard operating room lighting. There was greatly improved ability to resect labeled tumor tissue using FGS. CONCLUSIONS: Fluorophore-labeled anti-CEA or anti-CA 19-9 antibodies enable enhanced visualization of tumors for FGS of pancreatic cancer when CEA or CA 19-9 expression is present. The choice of fluorophore significantly affects the signal intensity in the labeled tumor. The technologies described herein have the potential to change the paradigm of surgical oncology to engender significantly improved outcomes. PMID- 26897961 TI - Management of Islet Cell Tumours: A Single Hospital Experience. AB - BACKGROUND/AIMS: Islet cell tumours (ICTs) are uncommon tumours in clinical practice. Surgical resection is the treatment of choice for ICTs, but localisation of these lesions can be challenging. The aim of this study was to analyse the clinical diagnosis and treatment for ICTs. METHODOLOGY: Thirty-one patients with ICTs who were diagnosed and who underwent surgical treatment in the affiliate hospital of Luzhou Medical College from 1 January 2000 to 31 July 2013 were enrolled. The clinical data of these patients were retrospectively reviewed. RESULTS: Among 31 patients (6 males, 25 females), 15 cases (48.39%) had non functional ICTs and 16 (51.61%) cases were insulinoma: The mean age of patients with non-functional ICTs was 42.73 +/- 12.34 years and of those with insulinoma was 48.88 +/- 13 years. Non-functional ICTs had a non-specific presentation. Insulinoma makes different clinical presentations mostly with symptoms of hypoglycaemia. CONCLUSIONS: Preoperative and/or intra-operative localisation is needed for ICTs; CT scan or MRI is used routinely as the first choice. If the lesion is very small, DSA is also good for localisation before operation. IOUS is a reliable technique in exactly localising insulinoma. ICTs are considered to be cured with successful surgical removal. PMID- 26897962 TI - Gastric Remnant Cancer: Continuing Serious and Insidious Problem for Surgeons. AB - BACKGROUND/AIMS: Gastric remnant cancers (GRC) are usually detected at a later stage resulting in low rates of curative resection and a consequently poor prognosis. The incidence and etiology of GRC have been changing recently because of early detection and improved outcomes in patients with gastric cancers. This study was performed to evaluate the clinicopathological characteristics and prognosis of patients with GRC. METHODOLOGY: From January 2004 and July 2014, 27 patients with GRC who underwent surgery were analyzed retrospectively. The clinicopathological and follow-up data of 27 patients were evaluated including age, gende types of reconstruction, tumor location, histological types, TNM stages, surgical treatment and prognosis. RESULTS: Total 221 patients underwent gastrectomy for gastric cancer and ulcer disease and 27 (12.7%) consecutive GRC patients were included in this study. The median survival for all 27 patients was 20.0 +/- 2.4 months. Previous malign disease, advanced TNM stage and non-curative resection were the negative prognostic factors for survival in patients with remnant stomach cancer (p < 0.05). CONCLUSIONS: Regular follow-up is one of the important factors affecting the early diagnosis and median survive time of patients with GRC. Curative resection is recommended operative treatment procedure to improve the survival when GRC patient diagnosed. PMID- 26897963 TI - Totally Laparoscopic D2 Radical Distal Gastrectomy Using Delta-Shaped Anastomosis: Initial Experience. AB - BACKGROUND/AIMS: We presented our preliminary clinical data for totally laparoscopic D2 radical distal gastrectomy using delta-shaped anastomosis (TLG DSA) to evaluate its effectiveness in terms of minimal invasiveness, technical feasibility, and safety for resection of early gastric cancer. METHODOLOGY: Five consecutive patients who underwent TLG-DSA in our institution from October 22th 2013 to November 29th 2013 were enrolled in this study. In all five cases, only laparoscopic linear staplers were used for intra-corporeal anastomosis. RESULTS: There were 3 men and 2 women, with a mean age of 67.6 years and a mean body mass index (BMI) of 21.4. All the patients with early gastric cancer were received TLG DSA. No postoperative complications were found in all five patients, and no postoperative mortality occurred. CONCLUSIONS: TLG-DSA using laparoscopic linear staplers for early gastric cancer was safe and feasible. Delta-shaped anastomosis is a simple, easy and safe method of intracorporeal gastroduodenostomy. PMID- 26897964 TI - EZH2 Mediates the Regulation of S100A4 on E-cadherin Expression and the Proliferation, Migration of Gastric Cancer Cells. AB - BACKGROUND/AIMS: Several reports have showed the inverse correlation between S100A4 and E-cadherin expression, but the exact molecular mechanism remained unclear. It has been reported that EZH2 mediates transcriptional silencing of E cadherin by trimethylating lysine 27 of histone H3 (H3K27me3). Therefore, we hypothesized that EZH2 might mediate the inhibition of S100A4 on E-cadherin and further affect the functions of S100A4 in gastric cancer cells. METHODOLOGY: RT PCR and Western Blot were used to detect the expression of EZH2 and E-cadherin after inhibiting or increasing S100A4 expression. MTT and Transwell assay were performed to detect the proliferation and migration of gastric cancer cells. RESULTS: Inhibition or overexpression of S100A4 led to decreased or increased EZH2 expression, and increased or decreased E-cadherin expression. The SET domain was important for EZH2 in rescuing the decreased proliferation and migration of the cells after S100A4 inhibition. CONCLUSION: As a novel downstream target of S100A4, EZH2 mediates the inhibition of S100A4 on E-cadherin. The SET domain is important for EZH2 in mediating the cellular function of S100A4. PMID- 26897965 TI - Laparoscopic Spleen-Preserving Splenic Hilar Lymph Node Dissection for Advanced Upper Gastric Cancer in Patients with High Body Mass Index. AB - BACKGROUND/AIMS: To evaluate the feasibility and safety of laparoscopic spleen preserving splenic hilar lymph node dissection for advanced upper gastric cancer in patients with high body mass index. METHODOLOGY: Outcomes were retrospectively analyzed in 140 patients with AUGC who underwent laparoscopic spleen-preserving splenic hilar LN dissection between January 2010 and December 2012, including those with high (>= 23 kg/m) and normal (< 23 kg/m2) BMI. RESULTS: Except for BMI, the clinicopathologic characteristics of patients with high and normal BMI were similar. The number of retrieved No. 10 LNs per patient was significantly lower in the high than in the normal BMI group. There were no significant between group differences in operation time, blood loss, postoperative hospital stay and complications. Subgroup analysis showed that the numbers of No. 10 LNs retrieved per patient were lower in males with high than normal BMI and in patients after the initial learning curve of 40 patients with high than normal BMI. CONCLUSIONS: Laparoscopic spleen-preserving splenic hilar LN dissection is feasible and safe in patients with high BMI, although even experienced laparoscopic surgeons should take special care in these patients, especially in men. PMID- 26897966 TI - Treatment of Gastric Metaplasia or Dysplasia by Endoscopic Radiofrequency Ablation: A Pilot Study. AB - BACKGROUND/AIMS: Patients with gastric intestinal metaplasia and dysplasia are at increased risk of gastric cancer development. We tested the feasibility of using endoscopic radiofrequency ablation for the treatment of dysplasia and metaplasia in the stomach. METHODOLOGY: Patients who had histologically confirmed low-grade gastric dysplasia or IM were recruited. Endoscopic RFA was performed at 8 week intervals for a maximum of 3 sessions. All patients were followed up by endoscopy until 12 months post-RFA. The primary outcome was the complete eradication of dysplasia or IM on follow-up. Secondary outcome was adverse events related to RFA. RESULTS: A total of 12 patients were recruited. Four patients had low-grade dysplasia and the remaining 8 patients had non-dysplastic IM at baseline. At one year after RFA, complete eradication of dysplasia was noted in four patients with low-grade dysplasia (100%). Gastric IM persisted in all patients with baseline metaplasia but the severity of IM improved in 6 (75%) patients. Endoscopic RFA was safe with minimal complications encountered. CONCLUSIONS: RFA successfully eradicated low-grade dysplasia of the stomach. Gastric IM however persisted after RFA but most patients had evidence of histological improvement on follow up. PMID- 26897967 TI - Laparoscopic Total Gastrectomy for Remnant Gastric Cancer Following Distal Gastrectomy with Radical Lymphadenectomy. AB - BACKGROUND/AIMS: In cases of remnantgastric cancer (RGC) with previous lymphadenectomy, laparoscopic total gastrectomy (LTG) is still uncommon because of the technical difficulties associated with adhesions from previous gastric cancer surgery and variations in anastomotic reconstruction. Here we demonstrate our procedure of LTG for RGC following distal gastrectomy (DG) with radical lymphadenectomy and review its clinical results. METHODOLOGY: From October 2008 to June 2014, we carried out three consecutive LTGs for RGC with previous lymphadenectomy. All cases had a past history of primary gastric cancer that had required open or laparoscopic DG with D2 radical lymphadenectomy. The preoperative TNM statuses of RGC were all cT1N0M0. RESULTS: All patients successfully underwent LTG without open conversion or intraoperative complications. The median operative duration was 360 min; the median blood loss was 45 mL. The median number of retrieved lymph nodes was 23. No complications occurred postoperatively, and the median length of postoperative hospitalization was 20 days. The pathological TNM statuses of the RGC were all T1N0M0. Resection margins were negative in all cases (R0). CONCLUSIONS: Our novel procedure of LTG for RGC following DG with radical lymphadenectomy is technically acceptable, safe, and feasible. PMID- 26897968 TI - Laparoscopy-Assisted D2 Radical Gastrectomy for Advanced Gastric Cancer. AB - BACKGROUND/AIMS: The aim of this study was to investigate the efficacy and advantages of laparoscopy-assisted gastrectomy (LAG) with D2 lymphadenectomy versus conventional open D2 gastrectomy (ODG) in advanced gastric cancer (AGC) patients. METHODOLOGY: From June 2009 to June 2014, 233 patients who were treated by conventional radical ODG and 188 cases who underwent radical LAG for AGC at our department were enrolled in this study. Clinical data recorded in hospital database was retrospectively reviewed and analyzed. RESULTS: There were no significant differences in age, gender or preoperative laboratory tests distribution between the LAG group and the ODG group. Two (1%) of the patients who underwent LAG required conversion to ODG. The advantages of minimally invasive surgery including earlier recovery of bowel movements and shorter postoperative hospitalization time were observed in LAG group. The number of harvested lymph nodes was 24.3 +/- 3.3 in the LAG group and 25.0 +/- 2.8 in ODG (p = 0.110). CONCLUSIONS: Although prospective randomized trials with long follow up period are needed to identify the feasibility, we have shown the safety and advantages of LAG with D2 lymphadenectomy for treating AGC patients in this study. PMID- 26897969 TI - Clinicopathological Parameters Influence Assessment of FDG SPECT in Gastric Cancer. AB - BACKGROUND/AIMS: To investigate the clinicopathological parameters influencing assessment of FDG SPECT in gastric cancer. METHODOLOGY: The frames of FDG SPECT and clinical data of 105 patients with gastric cancer were collected. The univariate and multivariate analyses were performed to assess the relationship between the visual assessment, SUV(max) and clinicopathological parameters. RESULTS: There were statistically significant in tumor size and pT stage between the positive and negative group (p < 0.01), while there was no statistically significant in gender, age, tumor localization, pN stage, histological type, adenocarcinoma differentiation (p > 0.05). Tumor size and pT stage were independent factors associated with visual assessment at multivariate analyses (p < 0.05). SUV(max) was positively correlated with age, tumor size and pT stage, respectively (p < 0.01). There was no statistically significant of SUV(max) in gender, tumor localization, pN stage, histological type, adenocarcinoma differentiation (p > 0.05). Age, tumor size and pT stage were independent factors related to SUV(max) (p < 0.05). CONCLUSIONS: Tumor size and depth of invasion were clinicopathological parameters influencing FDG SPECT assessment in gastric cancer independently. The relationship between tumor size, depth of invasion, expression of GLUT-1 and FDG imaging should be determined by further research. PMID- 26897970 TI - Risk Factors and Survival Outcomes for Postoperative Pulmonary Complications in Gastric Cancer Patients. AB - BACKGROUND/AIMS: Facing with the high incidence rate and the poor outcomes of the postoperative pulmonary complications (PPCs), we sought to evaluate potential risk factors for developing the PPCs of gastric cancer patients. METHODOLOGY: Retrospective study was carried out to analyze consecutive gastric cancer patients who had a preoperative pulmonary function test and underwent gastrectomy in the West China Hospital (January, 2000 - December, 2009). Potential risk factors to the development of the PPCs and the survival outcomes of these patients were also analyzed. RESULTS: Totally, one hundred and twenty four patients (18.1%) were developed the PPCs after gastrectomy. For the development of the PPCs, univariate analysis identified the following risk factors is associated with the development of the PPCs: age >= 70 years (p < 0.001); male patients (p = 0.041); FEV1/FVC < 60 (p < 0.001); with the history of pulmonary disease (p < 0.001); hemoglobin < 90g/L (p = 0.025); serum albumin < 35g/L (p = 0.002); combined organoectomy (p = 0.036). Multivariate analysis identified FEV1/FVC < 60 (p = 0.004); with the history of pulmonary disease (p < 0.002); serum albumin < 35g/L (p = 0.004) were risk factors for the incidence of the PPCs. CONCLUSIONS: For the early detection of the PPCs, extra attention should be paid to those gastric cancer patients with FEV1/FVC < 60; history of pulmonary disease and .serum albumin < 35g/L. PMID- 26897971 TI - Management of Islet Cell Tumours: A Single Hospital Experience. AB - BACKGROUND/AIMS: Islet cell tumours (ICTs) are uncommon tumours in clinical practice. Surgical resection is the treatment of choice for ICTs, but localisation of these lesions can be challenging. The aim of this study was to analyse the clinical diagnosis and treatment for ICTs. METHODS: Thirty-one patients with ICTs who were diagnosed and who underwent surgical treatment in the affiliate hospital of Luzhou Medical College from 1 January 2000 to 31 July 2013 were enrolled. The clinical data of these patients were retrospectively reviewed. RESULTS: Among 31 patients (6 males, 25 females), 15 cases (48.39%) had non functional ICTs and 16 (51.61%) cases were insulinoma. The mean age of patients with non-functional ICTs was 42.73 +/- 12.34 years and of those with insulinoma was 48.88 +/- 13 years. Non-functional ICTs had a non-specific presentation. Insulinoma makes different clinical presentations mostly with symptoms of hypoglycaemia. CONCLUSIONS: Preoperative and/or intra-operative localisation is needed for ICTs; CT scan or MRI is used routinely as the first choice. If the lesion is very small, DSA is also good for localisation before operation. IOUS is a reliable technique in exactly localising insulinoma. ICTs are considered to be cured with successful surgical removal. PMID- 26897972 TI - Internet Addiction and Attention Deficit Hyperactivity Disorder Among Schoolchildren. AB - BACKGROUND: Use of the internet and videogames by children and adolescents has risen dramatically over the last decade. Increasing evidence of internet and videogame addiction among children is causing concern due to its harmful physical, emotional and social consequences. There is also emerging evidence for an association between computer and videogame addiction and attention deficit/hyperactivity disorder (ADHD). OBJECTIVES: To investigate the relationship between ADHD and internet addiction. METHODS: We compared 50 male schoolchildren, mean age 13 years, diagnosed with ADHD to 50 male schoolchildren without ADHD on measures of internet addiction, internet use and sleep patterns. RESULTS: Children with ADHD had higher scores on the Internet Addiction Test (IAT), used the internet for longer hours, and went to sleep later than those without ADHD. CONCLUSIONS: These findings indicate an association of ADHD, sleep disorders and internet/videogame addiction. PMID- 26897973 TI - D1 versus D2 Gastrectomy for Gastric Adenocarcinoma. AB - BACKGROUND: Despite the ongoing decrease in the incidence of gastric cancer, this disease is still a major cause of death. It is still debatable whether D2 lymphadenectomy improves survival and whether this procedure should be performed routinely or selectively. OBJECTIVES: To compare the pathological and short-term results following radical D2-type gastric resection and lymphadenectomy versus the more limited D1 type resection and lymphadenectomy. METHODS: We conducted a retrospective study on 4 years experience treating 164 patients suffering from gastric cancer. We compared the results between the group of patients who underwent a radical D2 type gastric resection and lymphadenectomy (n = 100) and those of a relatively small group of patients who intentionally underwent the more limited D1 type (n = 34). RESULTS: The overall number of harvested lymph nodes was 9 +/- 4 in the D1 group compared to 30 +/- 12 (range 16-69) in the D2 group (P = 0.001). Of the 100 patients undergoing a D2 lymphadenectomy, 57% had positive nodes compared to 38% of the 34 patients in the D1 group (P = 0.045). CONCLUSIONS: We showed statistically significant differences between D1 and D2 procedures in the overall number of harvested lymph nodes and the proportion of positive nodes to the overall number. Our results support the fact that D2 resection should be recommended as the standard approach of treatment for gastric cancer patients, ensuring a larger number of retrieved lymph nodes and a comparable rate of complications and mortality. PMID- 26897974 TI - Diffusing Pulmonary Capacity Measured During Effort: A Possible Early Marker of Pulmonary Involvement In Systemic Sclerosis. AB - BACKGROUND: Interstitial lung involvement is common and potentially limits the quality of life in patients with systemic limited sclerosis (SScl). OBJECTIVES: To study the lung carbon monoxide diffusion (DLCO) measured during effort in order to identify a possible subclinical impairment. METHODS: We enrolled 20 SScl patients without interstitial lung involement and 20 healthy controls. At enrolment all subjetcs underwent plethysmography, DLCO by single-breath technique, and evaluation of pulmonary blood flow (Qc) with the rebreathing CO2 method. Skin involvement in the SScl patients was rated using the modified Rodman skin score (mRSS). During exercise on a cycle ergometer, DLCO, DLCO/ alveolar volume (Kco) and Qc were calculated at 25% and 50% of predicted maximum workload (25% pmw and 50% pmw). RESULTS: At baseline two groups did not differ in age, body mass index, lung function or Qc. In the controls, DLCO, Kco and DLCO/Qc measured at 25% pmw and 50% pmw were significantly higher than in SScl patients, while Qc was not different. Based on response to effort, SScl patients were divided into two groups: responders, with an increase of DLCO(25%pmw) and DLCO(50%pmw) at least 5% and 10% respectively, and non-responders. The non responders showed greater skin involvement and significantly reduced DLCO, Kco and DLCO/Qc values at rest than responders. CONCLUSIONS: Moderate effort in SScl patients may reveal a latent impairment in gas diffusion through the alveolar/capillary membrane, thus confirmig that exertional DLCO can identify lung damage at an earlier stage than DLCO at rest. PMID- 26897975 TI - Cardiac Hypertrophy and Cardiac Cell Death in Chronic Kidney Disease. AB - BACKGROUND: Chronic kidney disease (CKD) is a prevalent clinical condition affecting 15% of the general population. Cardiorenal syndrome (CRS) type 4 is characterized by an underlying CKD condition leading to impairment of cardiac function and increased risk for major cardiovascular events. To date, the mechanisms leading from CKD to CRS are not completely understood. In particular, it is unclear whether the pathological changes that occur in the heart in the setting of CKD involve enhanced cell death of cardiac cells. OBJECTIVES: To assess whether CKD may mediate loss of cardiac cells by apoptosis. METHODS: We established rat models for CKD, acute myocardial infarction (acute MI), left ventricular dysfunction (LVD), and sham. We measured the cardiac-to-body weight as well as kidney-to-body weight ratios to validate that renal and cardiac hypertrophy occur as part of disease progression to CRS. Cardiac cells were then isolated and the percent of cell death was determined by flow cytometry following staining with annexin-FITC and propidium iodide. In addition, the levels of caspase-3-dependent apoptosis were determined by Western blot analysis using an anti-cleaved caspase-3 antibody. RESULTS: CKD, as well as acute MI and LVD, resulted in significant cardiac hypertrophy. Nevertheless, unlike the increased levels of cell death observed in the acute MI group, in the CKD group, cardiac hypertrophy was not associated with induction of cell death of cardiac cells. Caspase-3 activity was even slightly reduced compared to sham-operated controls. CONCLUSIONS: Our data show that while CKD induces pathological changes in the heart, it does not induce cardiac cell death. PMID- 26897976 TI - Lamellar Macular Holes Associated with End-Stage Exudative Age-Related Macular Degeneration. AB - BACKGROUND: Reports of lamellar macular holes (LMHs) with underlying age-related macular degeneration (AMD) are rare, and the specific definition, pathogenesis and surgical recommendations for this macular condition remain unclear. OBJECTIVES: To present a series of LMHs in eyes with underlying end-stage AMD, and describe optical coherence tomography (OCT) detection of associated morphologic abnormalities. METHODS: We reviewed the files of consecutive patients diagnosed with LMH and underlying end-stage AMD between September 2007 and September 2011. RESULTS: Sixteen eyes of 14 patients were included in this study. The average follow-up after the OCT-established diagnosis of LMH was 19.8 months (range 4-48). The average visual acuity (VA) at last follow-up visit was 20/400 (20/60-20/1200). The best-corrected VA was stable in 10 eyes (62.5%) and deteriorated in 6 (37.5%). There was a statistically significant correlation between VA and minimal foveal thickness (r = -0.598, P = 0.014). CONCLUSIONS: In this series of LMHs with underlying AMD the OCT findings were intraretinal fluid, cystic spaces and window defect. PMID- 26897977 TI - Establishment of a Registry to Monitor Trends in Cataract Surgical Procedures and Outcomes in Israel, 1990-2014. AB - BACKGROUND: Cataract extraction is the most commonly performed ophthalmic surgical procedure. There is no registry for documenting cataract surgical procedures and the overall risk of its complications overtime in Israel. OBJECTIVES: To present trends in the number and type of selected parameters associated with cataract surgical procedures in Israel between 1990 and 2014. METHODS: Questionnaires had been sent annually to all surgical centers in which cataract surgery was performed in Israel during the study period. The trends that were investigated included annual rates, surgical sites, surgical techniques, use of an intraocular lens (IOL), and type and rates of postoperative endophthalmitis (POE). RESULTS: A total of 812,112 cataract surgical procedures were reported during the 25 year study period. Responses to the questionnaire increased from 75% in 1990 to 100% in 2006 onwards. The annual number of reported cataract surgical procedures increased from 16,841 (3.5 per 1000) in 1990 to 57,419 in 2014 (6.9 per 1000), representing an increase of 197%. There was a shift from performing the surgery in the public health system to private medical centers. The surgical technique changed from predominantly manual extracapsular cataract extraction (56% in 1999) to predominantly phacoemulsification (98.7% in 2014). POE rates decreased from 0.25% in 2002 to 0.028% in 2014. CONCLUSIONS: There was a continuous increase in the rate of surgical cataract procedures, and more were performed in private medical facilities. There was also a major shift towards advanced cataract procedures and a decreased rate of POE. PMID- 26897978 TI - Incidence of Implantable Cardioverter Defibrillator Therapy and Mortality in Primary and Secondary Prevention of Sudden Cardiac Death. AB - BACKGROUND: Implantable cardioverter defibrillators (ICDs) reduce mortality in patients implanted for primary and secondary prevention of sudden cardiac death. Data on the incidence of appropriate ICD therapies in primary vs. secondary prevention are limited. OBJECTIVES: To compare ICD therapies and mortality in primary vs. secondary prevention of sudden cardiac death. METHODS: We conducted a retrospective analysis of 581 consecutive patients receiving an ICD for primary (66%) or secondary (34%) prevention indications. RESULTS: During long-term follow up, 29% of patients implanted for secondary prevention received appropriate ICD therapy vs. 18% implanted for primary prevention. However, the overall 7 year mortality rate was not significantly different between the two groups (26.9%, P = 0.292). Multivariate analysis showed that patients implanted for primary prevention had a significantly lower risk of appropriate ICD therapy even after adjustment for age, left ventricular ejection fraction < 0.35 and chronic renal failure (HR 1.63, 95% CI 1.10-2.41, P = 0.015). CONCLUSIONS: Patients implanted for secondary prevention were more likely to receive appropriate ICD therapy, with a significantly shorter time period from ICD implant to the first therapy. However, all-cause mortality was comparable between primary and secondary prevention groups. PMID- 26897979 TI - Non-Valvular Findings before Trans-Catheter Aortic Valve Implantation and their Impact on the Procedure. AB - Background: Trans-cathetervalve implantation (TAVI) is a non- surgical alternative for patients with severe aortic stenosis (AS). Pre-procedural computed tomography angiography (CTA) allows accurate "road mapping," aortic annulus sizing and the detection of incidental findings. OBJECTIVES: To document the prevalence of non-valvular extracardiac findings on CTA prior to TAVI and the impact of these findings on the procedure. METHODS: Ninety AS patients underwent CTA as part of pre-TAVI planning. Scans extended from the clavicles to the groin. Non-vascular non-valvular findings were documented and graded as follows: (A) significant findings causing TAVI cancellation or postponement, (B) significant findings leading to a change in the TAVI procedure approach, (C) non-significant findings not affecting the TAVI procedure. RESULTS: TAVI was planned for 90 patients; their average age was 80.2 +/- 7.5 years, 53% were females. Overall, non-valvular cardiac, extracardiac and extravascular significant and non significant incidental findings were documented in 97% of scans (87/90). Significant pathologies causing TAVI cancellation or postponement (category A) were documented in 8%. Significant findings affecting the TAVI procedure (category B) were found in 16% of patients. CONCLUSIONS: Pre-TAVI CTA detected non-valvular extravascular pathologies leading to procedure cancellation/postponement or procedure modification in 8% and 16%, respectively. Comprehensive CTA evaluation that acknowledges the importance of such findings is of major importance since it might alter the TAVI procedure or even render it inappropriate. PMID- 26897980 TI - The Road to Modified D2 Gastrectomy. PMID- 26897981 TI - Non-Radiographic Axial Spondyloarthritis. AB - The term non-radiographic axial spondyloarthritis (nrAxSpA) was coined for patients who have a clinical picture of ankylosing spondylitis (AS) but do not exhibit radiographic sacroiliitis. The ASAS classification criteria for nrAxSpA, ensuring the recruitment of homogenous study cohorts, were accepted in 2009, although the respective diagnostic criteria for daily clinical practice have not yet been developed. The clinical diagnosis should be based on the composite of clinical symptoms and signs of the disease, HLA B27 status, and magnetic resonance imaging (MRI) of sacroiliac joints. Notably, a negative MRI or HLA B27 does not exclude the diagnosis in patients with a high clinical suspicion for nrAxSpA. The prevalence of nrAxSpA is similar to that of AS, but the former has a higher female preponderance. The rate of progression of nrAxSpA to the radiographic stage of disease (AS) ranges from 10% to 20% over 2 years. Current treatment strategies for nrAxSpA are the same as for AS and include non-steroidal anti-inflammatory drugs and inhibitors of tumor necrosis factor-alpha. While this review summarizes the current achievements in the field of nrAxSpA, further understanding of the epidemiology and natural history of the disease and, particularly, mechanisms of inflammation and subsequent new bone formation is essential for the development of new treatment strategies for nrAxSpA patients. PMID- 26897982 TI - Vascular Aneurysm Secondary to a Femoral Intertrochanteric Fracture Concealed by Anticoagulation Therapy. PMID- 26897983 TI - Cast Nephropathy in the Setting of Diffuse Carcinomatosis of Unknown Origin. PMID- 26897985 TI - Systemic Generalized Lymphangiomatosis: A Diagnostic Challenge. PMID- 26897984 TI - Recurrent Pericarditis: An Autoinflammatory Disease? PMID- 26897986 TI - A Huge Melanoma. PMID- 26897987 TI - Cameraman's Foot. PMID- 26897988 TI - Sequential Therapy with PEG-IFN alpha-2a and Tenofovir in a Hepatitis B Virus Infected African Man. PMID- 26897989 TI - LOWER SATISFACTION AMONG HOSPITALS THAT DISPROPORTIONATELY TREAT BLACK PATIENTS. PMID- 26897990 TI - FAMILY DEVELOPMENT CREDENTIAL TRAINING IMPACT ON SELF-EFFICACY BELIEFS OF HUMAN SERVICE WORKERS. AB - The Family Development Credential (FDC) Training offers an innovative interagency training for human service workers within a community. We use a mixed-methods approach to evaluate the impact of FDC on work-related self-efficacy beliefs. Quantitative data found FDC participants increased their levels of positive self efficacy beliefs and had no change in negative self-efficacy beliefs; a comparison group saw no change in positive self-efficacy beliefs but increased their levels of negative self-efficacy beliefs. Qualitative data indicated training increased work-related self-efficacy beliefs. Overall, findings suggest that FDC training improved self-efficacy in human service workers and that no training allowed negative self-efficacy beliefs to grow. PMID- 26897991 TI - PERSPECTIVES ON MULTIDISCIPLINARY TEAM PROCESSES AMONG HEALTHCARE EXECUTIVES: PROCESSES THAT FACILITATE TEAM EFFECTIVENESS. AB - BACKGROUND: Multidisciplinary teams (MDTs) are used in healthcare organizations to address both clinical and managerial functions. Despite their prevalence, little is known about how team processes work to facilitate effectiveness among MDT leadership teams. PURPOSE: This study explores perceptions of MDT participation experienced by organizational leaders in healthcare organizations in the United States. METHODOLOGY/APPROACH: A survey of American College of Healthcare Executives members was conducted to assess involvement and perceptions of MDTs among health care management professionals. Descriptive statistics, independent T-Tests and Chi-square analyses were used to examine participation in MDTs, perception of MDT processes, and the association of participation and perceived processes with employee and organizational characteristics. FINDINGS: The survey yielded a sample comprised of 492 healthcare executive or executive track employees. An overwhelming majority indicated participation in MDTs. The study identified team processes that could use improvement including communication, cooperation, and conflict resolution. PRACTICE IMPLICATIONS: The study provides evidence that can help guide the development of training programs that focus on providing managerial leaders with strategies aimed at improving communication, coordination, and conflict resolution that will improve the effectiveness of MDT functioning in healthcare organizations. PMID- 26897992 TI - FEE-SCHEDULE INCREASES IN CANADA: IMPLICATION FOR SERVICE VOLUMES AMONG FAMILY AND SPECIALIST PHYSICIANS. AB - Physician spending has substantially increased over the last few years in Canada to reach $27.4 billion in 2010. Total clinical payment to physicians has grown at an average annual rate of 7.6% from 2004 to 2010. The key policy question is whether or not this additional money has bought more physician services. So, the purpose of this study is to understand if we are paying more for the same amount of medical services in Canada or we are getting more bangs for our buck. At the same time, the paper attempts to find out whether or not there is a productivity difference between family physician services and surgical procedures. Using the Baumol theory and data from the National Physician Database for the period 2004 2010, the paper breaks down growth in physician remuneration into growth in unit cost and number of services, both from the physician and the payer perspectives. After removing general inflation and population growth from the 7.6% growth in total clinical payment, we found that real payment per service and volume of services per capita grew at an average annual rate of 3.2% and 1.4% respectively, suggesting that payment per service was the main cost driver of physician remuneration at the national level. Taking the payer perspective, it was found that, for the fee-for-service (FFS) scheme, volume of services per physician decreased at an average annual rate of -0.6%, which is a crude indicator that labour productivity of physicians on FFS has fallen during the period. However, the situation differs for the surgical procedures. Results also vary by province. Overall, our finding is consistent with the Baumol theory, which hypothesizes higher productivity growth in technology-driven sectors. PMID- 26897993 TI - Social Workers Paving the Way for Change One Client at a Time. PMID- 26897994 TI - U.S. Social Worker Workforce Report Card: Forecasting Nationwide Shortages. AB - Using age-based projected changes in population, the authors developed demand and supply models of the social worker workforce to project the shortage of social workers in all 50 states and assigned letter grades based on shortage ratios. According to the projections, the number of states with shortage ratios more severe than the current national ratio will increase from 11 states in 2012 to 30 states by 2030 and the nation will experience a total shortfall of over 195,000 social workers, with the most severe shortages occurring in the western and southern regions of the United States. Further efforts are recommended to investigate shortage dynamics and develop strategies to counter its causes. PMID- 26897995 TI - Assessing the National School Social Work Practice Model: Findings from the Second National School Social Work Survey. AB - The Second National School Social Work Survey in 2014 aimed to update knowledge of school social work practice by examining how practitioner characteristics, practice context, and practice choices have evolved since the last national survey in 2008. This second survey was also developed to assess how the new national school social work practice model created by the School Social Work Association of America aligns with early 21st century school social work practice realities. The second survey was conducted from February through April 2014 (3,769 total responses were collected) and represents the largest sample of American school social workers surveyed in two decades. Data from the Second National School Social Work Survey showed a field that still has not fully responded to calls to implement evidence-informed and data-driven practices. This article notes the need to better integrate pre- and postservice training in data driven practices and provides recommendations for ways to overcome barriers that school social workers report facing. PMID- 26897996 TI - Living Up to the Code's Exhortations? Social Workers' Political Knowledge Sources, Expectations, and Behaviors. AB - The National Association of Social Workers' (NASW's) Code of Ethics urges social workers to engage in political action. However, little recent research has been conducted to examine whether social workers support this admonition and the extent to which they actually engage in politics. The authors gathered data from a survey of social workers in Austin, Texas, to address three questions. First, because keeping informed about government and political news is an important basis for action, the authors asked what sources of knowledge social workers use. Second, they asked what the respondents believe are appropriate political behaviors for other social workers and NASW. Third, they asked for self-reports regarding respondents' own political behaviors. Results indicate that social workers use the Internet and traditional media services to stay informed; expect other social workers and NASW to be active; and are, overall, more active than the general public in many types of political activities. The comparisons made between expectations for others and their own behaviors are interesting in their complex outcomes. Social workers should strive for higher levels of adherence to the code's urgings on political activity. Implications for future work are discussed. PMID- 26897997 TI - Permanency-Focused Supervision and Workers' Self-Efficacy: Exploring the Link. AB - Child welfare agencies are charged with the mission of establishing timely legal permanency for all children in out-of-home care. National data indicate that the field of child welfare continues to struggle to fulfill this mission. Pragmatic strategies to improve permanency outcomes are essential. This study used cross sectional data (N = 427) to examine the relationship between workers'self efficacy in making permanency decisions and the supervision they receive. Child welfare supervisors monitor and mentor their supervisees' work and are responsible for practice outcomes, including establishing timely permanency. Supervision also contributes to the self-efficacy of frontline child welfare workers. Findings suggest that when supervisors focus their supervision on permanency outcomes, workers report a higher level of self-efficacy in making permanency decisions. This finding provides encouraging implications for child welfare agencies in developing innovative approaches to improving permanency outcomes while relying on existing resources. PMID- 26897998 TI - Depression among Muslims in the United States: Examining the Role of Discrimination and Spirituality as Risk and Protective Factors. AB - Depression is a widespread challenge that affects people in all cultures. Yet, despite the growth of the Muslim population in the United States, little research has been conducted on this topic with members of this cultural group. To address this gap in the literature, the present study examines the effect of discrimination and spirituality on depression with a sample of self-identified Muslims (N = 269). Consistent with our expectations, discrimination was a risk factor and spirituality was a protective factor. For instance, Muslims who reported being called offensive names were more likely (odds ratio [OR] = 3.39, 95% confidence interval [CI] = 1.82, 6.32) to report clinically significant levels of depressive symptoms compared with those who were not called offensive names, whereas saying daily prayers was associated with a lower likelihood of reporting elevated levels of symptoms (OR = 0.74, 95% CI = 0.55, 0.97). The article concludes with a discussion of the implication of the results as they intersect social work practice and of avenues for future research. PMID- 26897999 TI - Psychosocial Equine Program for Veterans. AB - Nearly half of all combat veterans suffer from serious psychological disorders and reintegration issues. Veterans shy away from typical talk therapy and are seeking alternative treatments. Equine-facilitated mental health therapy has shown promise in treating veterans with depressive and anxiety disorders and reintegration issues. This article reports on an institutional review board approved pilot program designed to address the mental health needs of veterans. Furthermore, this article discusses future directions for evolving development of equine treatment programming. PMID- 26898000 TI - Saving Satir: Contemporary Perspectives on the Change Process Model. AB - Virginia Satir continues to be a highly influential figure in family therapy. The summation of her decades of work with families, the Satir growth model (SGM), remains a relevant therapeutic approach that is still practiced by many. This narrative review sought to examine (a) the core therapeutic methods developed by Satir for working with families, and (b) the empirical evidence to support the use of such methods. The author reviewed both firsthand and secondhand accounts of Satir's model of therapy, as well as extant research. Results from four included studies lend equivocal support for the continued use of Satir's approaches in contemporary family therapy. Implications for clinicians include the need for further refinement and systematization of the SGM. Also, researchers must empirically test Satir's methods using stronger methodology with larger and more diverse samples. In an age where evidence-based practice has become standard, all stakeholders must actively work to bolster the support for Virginia Satir's work, lest her important contributions to family therapy be forgotten due to insufficient evidence. PMID- 26898001 TI - Voices from Social Work Graduates in China: Reasons for Not Choosing Social Work as a Career. AB - Although previous studies have addressed turnover issues after being a social worker, this study identifies factors that may block initial entry to the profession. Using a semistructural interview method with 20 BSW graduates, the researchers transcribed the reasons for BSW graduates not entering a career in social work. Through element-centered content analysis, 76 reasons were sorted into nine categories: (1) income insufficient for basic needs, (2) unclear future, (3) no commitment to social work, (4) social work jobs could be taken by other professionals, (5) difficulties in actualizing proclaimed value, (6) personally unable to apply skills, (7) social exclusion due to nonresident status, (8) hard/stressful work, and (9) not supported by peers and family. Through person-centered content analysis, most respondents (90 percent) reported multiple reasons (M = 3.8) supporting their decision, offering their rational thought processes culminating in the decision not to enter social work. Recommendations for developing a national survey, engaging social workers in preparing BSW students for graduation, and modifying student admissions strategies are discussed. PMID- 26898002 TI - Confronting Barriers to Critical Discussions about Sexualization with Adolescent Girls. PMID- 26898003 TI - Military Culture and the Transition to Civilian Life: Suicide Risk and Other Considerations. PMID- 26898004 TI - Caught between Denial and Dollars: The Challenge of a Health Care Social Worker. PMID- 26898005 TI - Physical and Emotional Sibling Violence: A Necessary Role for Social Work. PMID- 26898006 TI - On Devolution. Better prepare for a less national health service. PMID- 26898007 TI - A Formula for Delivering the Forward View. PMID- 26898008 TI - Rethink the Staff-system Relationship. PMID- 26898009 TI - BIRTH OF A NEWBREED. PMID- 26898010 TI - PRACTICAL GAINS. PMID- 26898012 TI - CLINICAL NOTES. PMID- 26898011 TI - WORKFORCE. 'MANAGERS NEED TO RELEASE BRIGHT STAFF'. PMID- 26898013 TI - 'HAVING ROLE MODELS IS KEY'. PMID- 26898014 TI - Workforce. Getting a grip on staffing costs. PMID- 26898015 TI - SUSTAINABILITY. CUT YOUR ETHICAL FOOTPRINT. PMID- 26898016 TI - SUSTAINABILITY. CASE STUDIES. GREEN SHOOTS. PMID- 26898017 TI - SHAKEN FOUNDATIONS. PMID- 26898018 TI - [Quickly find the right solution--with specialists in behavior medicine]. PMID- 26898020 TI - [The Radar Bulletin of the Federal Bureau for Food Safety and Veterinary Essence: at the pulse of international animal epidemics]. PMID- 26898019 TI - [Stumbling blocks and dangers in buying puppies]. PMID- 26898021 TI - [Veterinarians in the field: the fight against drought and peste-des-petits ruminants]. PMID- 26898022 TI - [The continued payment of wages in the case of illness and sick day salary insurance]. PMID- 26898023 TI - [Vigilance of veterinary medicinal products: Reports of adverse reactions in the year 2014]. AB - During the year 2014, a total of 268 adverse reactions due to Swissmedic authorized veterinary medicinal products were reported representing an increase of 7% compared to the previous year. Similar to previous years, most of the reactions reported were linked to the use of antiparasitic products (47.8%) or antiinfectives (9.3%). In 10.8% of the reports, reactions were described after the use of products acting on the hormonal system. The affected animal species were primarily dogs (182 reports), cats (58 reports), and cattle (16 reports). Additionally, 33 reports were provided within the frame of consultations with the toxicological information centre in Zurich (Tox Info Suisse). We present a short overview of the safety of COX-2 inhibitors and a series of reactions following the use of a parenteral buprenorphine solution. Finally, the vaccinovigilance program received 124 declarations following the application of various vaccines, but no detailed analysis of those reports is available. PMID- 26898025 TI - [Health problems of domestic animals with suspicion of non-ionizing rays or electric current leakage as the cause: results of a questionnaire investigation]. PMID- 26898024 TI - [Investigation of metabolic parame- ters in high yielding dairy cows in pasture based production systems]. AB - In the present study differences in metabolism between New Zealand Holstein Friesian (NZHF) and Brown Swiss (CH-BV) or Swiss Holstein-Friesian (CH-HF) were investigated in a grassland based milk production system in Switzerland. Therefore 14 pairs of CH-BV/NZHF and 11 pairs of CH-HF/NZHF were available. The parameters glucose, insulin, non-esterified fatty acids (NEFA), beta hydroxybutyrate (beta-HB), urea and cholesterol were analysed at the times 5-3 weeks before the calculated partus and 2, 3, 5, 7, 10 and 18-22 weeks post partum. Only beta-HB showed significantly higher concentrations (P = 0.0059) for both Swiss breeds compared to the NZ-HF. Regarding all other physiological parameters during early lactation New Zealand Holstein-Friesians were not different from Swiss breeds. PMID- 26898026 TI - Phytotherapy in zoo animals. PMID- 26898027 TI - Introduction to verification of the GOHAI instrument for measuring the oral health-related quality of life in patients with dentures using the Serbian preliminary version--A pilot study. AB - BACKGROUND/AIM: Quality of life related to health should be seen as a multidimensional concept that, in addition to the physical symptoms associated with a disease and treatment, should include physical, psychological and social functioning of a person. The primary objective of this study was to use the Serbian preliminary version of the Geriatric Oral Health Assessment Index (GOHAI) questionnaire in oder to examine the consistency, reliability and stability, as well as an introduction to the verification tool. METHODS: The GOHAI questionnaire with 6-level Likert scale, translated into Serbian, including the relevant oral health characteristics (oral hygiene, required dentures, number of teeth extracted), was filled by five specialists in prosthodontics for 30 randomly selected respondents, before and after the dental prosthetic treatment. Subsequently, in order to measure the reliability of the questionnaire, 27 patients were re-interviewed. RESULTS: The value of Cronbach's Alpha Coefficient (Cralpha) before the treatment was 0.878, and after the treatment it was 0.788 confirming the internal consistency and stability of the questionnaire. The validity of discriminatory properties of the GOHAI was confirmed by the Spearman's correlation coefficient (r), which was highly significantly associated with oral health characteristics, confirming the high reliability of the measurement. The results of test-retest analysis measured by the individual Pearson's correlation coefficient (r) were in the range of 0.34-0.97, and for the total score r was 0.927, while the Kappa coefficient was 0.63. The correlation analysis of the GOHAI score before the treatment showed that for 10 questions there was a statistically significant correlation of the score with the answers to the questions, and for 6 questions Spearman's r was >= 0.7. After the treatment a highly significant correlation of the GOHAI was shown with the answers to 10 questions, while for 5 questions the Spearman's r was > 0.6. The GOHAI average score before the treatment was 19.44 +/- 11.12, and after the treatment 2.77 +/- 3.83, where the lower value indicates better quality of life. CONCLUSION: The results of this pilot study confirm internal consistency and stability of the Serbian preliminary version of the GOHAI questionnaire and the causal relation between the quality of life and the characteristics of oral health of the patients with dentures. Accordingly, instrument verification is recommended. PMID- 26898028 TI - Sweat rate and fluid intake in young elite basketball players on the FIBA Europe U20 Championship. AB - BACKGROUND/AIM: Previous investigations in many sports indicated that continued exercise, especially in hot environments, can cause high sweat rate and huge water and electrolyte losses, thus impairing the performance of athletes. Most these studies were conducted during training sessions, but rarely during an official competition. Therefore, the aim of our study was to determine pre- and post-competition hydration, fluid intake and sweat loss of young elite basketball players during the FIBA Europe U20 Championship. METHODS: The study included 96 basketball male players, (19 +/- 0.79 years) of eight national teams. Ambient temperature was 30 +/- 2 degrees C, humidity 55 +/- 4% and the mean playing time in game 18.8 +/- 10.5 min. The following parameters related to hydration status were measured: fluid intake, urine output, sweat rate, percent of dehydration, urine parameters (specific gravity, color and osmolarity), body mass and body surface area. RESULTS: We found that the mean fluid intake was 1.79 +/- 0.8 L/h, sweat rate 2.7 +/- 0.9 L/h, urine output 55 +/- 61 mL and the percentage of dehydration 0.99 +/- 0.7%. According to urine osmolarity more than 75% of players were dehydrated before the game and the process continued during the game. The difference in body mass (0.9 +/- 0.7 kg) before and after the game was statistically significant. There were statistically significant correlations between the sweat rate and fluid intake, urine osmolarity, body mass loss, body surface area and percentage of dehydration. Fluid intake correlated with the percentage of dehydration, body mass loss, urine specific gravity and urine color. The sweat rate, which varied between the teams, was the highest for centers when this parameter was calculated on the effective time in game. CONCLUSION: Most of the athletes start competition dehydrated, fail to compensate sweat loss during the game and continue to be dehydrated, regardless what kind of drink was used. These results suggest that hydration strategies must be carefully taken into account, not only by the players, but also by the coaches and the team doctors. PMID- 26898029 TI - Efficacy of botulinum toxin type A in treatment of different forms of focal dystonias in the Serbian population: experience of the Botulinum Toxin Outpatients Department. AB - BACKGROUND/AIM: Botulinum toxin (BTX) irreversibly inhibits presynaptic acetylcholine release with subsequent relaxation of abnormally contracting muscles. It is an effective and well tolerated treatment with long-term benefit in a variety of movement disorders and other neurological and non-neurological disturbances. The aim of our study was to present our experience with BTX type A in treatment of different forms of focal dystonias. METHODS: A hundred of patients with different focal dystonias (spastic torticollis, blepharospasm and graphospasm) from the Botulinum Toxin Outpatients Department, Clinic for Neurology, Clinical Center of Serbia, were included in the study. All the patients were examined and rated at baseline visit prior to BTX application and on the following visit, after 3-4 months, using self-assessment improvement questionnaire and standardized rating scales. RESULTS: . The improvement of 50% was presented in 68.2% of all (199) the analyzed applications. Independent predictors of good response to the therapy (improvement >= 50%) were male sex (p = 0.011), the presence of sensory trick (p = 0.013) and the total number of BTX applications (p = 0.002). The patients with spastic torticollis and blepharospasm showed a statistically significantly better BTX effect (improvement 57.3 +/- 27.5% and 54.1 +/- 28.3%), respectively than the graphospasm group (26.7 +/- 25.6%). Most of the patients did not have therapy complications (81.4% and 72% in two applications). Side effects in the remaining patients (muscle weakness, dysphagia, ptosis, double vision, neck weakness and lacrimal dysfunction) lasted for 28.3 +/- 18.6 days after the first treatment and 32.5 +/- 36.2 days after the second one. CONCLUSION: BTX is safe and highly effective in long-term treatment of patients with different forms of focal dystonia, with only mild and well tolerated side-effects. PMID- 26898030 TI - Analysis of the factors influencing development of urinary tract infections in patients with spinal cord injuries. AB - BACKGROUND/AIM: Urinary tract infections are still the most frequent complications in patients with spinal cord injury (SCI). The aim of this study was to analyze the factors influencing development of urinary tract infections during rehabilitation in patients with SCI. METHODS: This retrospective case/control study including 540 patients with SCI which were rehabilitated in the Clinic for Rehabilitation "Dr Miroslav Zotovic" between January 2000 and December 2009. We used patient files and other available medical documentation for obtaining information contained in this study, such as the manner of bladder emptying, the type of neurological disorder of the bladder, the neurological level and completeness of a lesion, the injury etiology, treatment method, secondary complications and associated injuries, kidney and bladder calculosis, age and sex. RESULTS: Out of the total number of patients included in the study, 152 (28.1%) were without urinary tract infections, whereas 388 (71.9%) had urinary tract infections. There were 389 (72%) male and 151 (28%) female patients. The average age of patients without urinary tract infections was 51.0 +/- 15.4 years, whereas the mean age of patients with urinary tract infections was 44.3 +/- 16.9 years. The results of our study showed that the occurrence of urinary tract infections during rehabilitation in patients with SCIs was associated with the following factors: combined injuries (OR = 3.5), anemia (OR = 5.67), type of the bladder functional disorder (OR = 40-60) and crystals in urine (OR = 7.54). CONCLUSION: The physicians should take precautions and try to make the early diagnosis and rapid appropriate treatment of urinary tract infections in patients with SCI who also have functional bladder disorder, combined spinal injuries, anemia or urine crystals. PMID- 26898031 TI - Diuretic 99mTc DTPA renography in assessment of renal function and drainage in infants with antenatally detected hydronephrosis. AB - BACKGROUND/AIM: The controversy over the postnatal management of infants with antenataly detected hydronephrosis (ANH) still exists. We presented the results of diuretic 99mTc diethylenetriamine pentaacetic acid (DTPA) renography in 30 infants with the antenatal diagnosis of unilateral renal pelvic dilatation. The aim of this study was to assess the renal function determined by the pattern of drainage and split renal function (SRF) on diuretic renography and to correlate these findings with anteroposterior pelvic diameter (APD) estimated by ultrasonography. METHODS: A total of 30 infants with 60 renal units (RU) (25 boys and 5 girls, median age 6.0 months, range 2-24) presented with unilateral hydronephrosis on ultrasound in the newborn period, underwent DTPA diuretic renal scintigraphy (F+15 protocol). The median APD evaluated on perinatal ultrasound was 15 mm (range 5-30). The postnatal associated clinical diagnosis were pelviureteric junction obstruction (PUJ), simple hydronephrosis, megaureter, vesicoureteral reflux (VUR) and posterior urethral valves in 11, 10, 6, 2 and 1 infant, respectively. Images and Tmax/2 after diuretic stimulation on the background subtracted renographic curves were used as the criteria for classifying the drainage as good, partial, and poor or no drainage. The SRF was calculated with the integral method. RESULTS: Good drainage was shown in 36/60, partial drainage in 13/60 and poor or no drainage in 11/60 RU. The SRF > 40% was observed in 55/60 RU, with no RU showing SRF lower than 23.5%. In infants with severe ANH the obstruction was not excluded in 94.1%. CONCLUSION: Diuretic renography in antenatally detected hydronephrosis should be a useful tool in postnatal follow up, especially in differentiating nonobstructive hydronephrosis from obstructive. It is also importanat to assess and monitor the SRF. Our results suggest that even in the presence of partial or no drainage, SRF may not be significantly impaired. PMID- 26898032 TI - The effect of antipsychotic drugs on nonspecific inflammation markers in the first episode of schizophrenia. AB - BACKGROUND/AIM: Immune system disorder, including inflammation, takes a significant place when considering still unclear etiology of schizophrenia. The aim of this study was to determine the blood levels of nonspecific inflammation markers in the first episode of schizophrenia and their relation to the therapy response. METHODS: In this study we determined the blood levels of nonspecific inflammation markers: white blood cells count (WBC), C-reactive protein (CRP), erythrocytes sedimentation rate (ESR) and the elements of differential white blood cell counts (or the leukocyte formula): granulocytes (Gra), lymphocytes (Lym) and monocytes (Mon), in the first episode of schizofrenia, in 78 patients hospitalized at the Clinic for Psychiatric Disorders "Dr Laza Lazarevic" in Belgrade. The levels were measured at admission to the clinic, as well as after 4 weeks of antipsychotic treatment. The Positive and negative syndrome scale for schizophrenia (PANSS) was applied to measure the severity of psychopathology and response to the treatment. RESULTS: During the first episode of schizophrenia, before initiation of antipsychotic treatment, the frequency of abnormal values was high (>= 25% of the patients) for the following non-specific inflammation markers: WBC, CRP, ESR and Gra, in the leukocyte formula, but dropped after 4 weeks of antipsychotic treatment at the level of high statistical significance for WBC and Gra (p < 0.001). The ESR remained unchanged in as many as 50% of the patients even after 4-week antipsychotic treatment, at the level of statistical significance in the non-responders compared to the responders (p = 0.045). CONCLUSION: The obtained results indicate that in the first episode of schizophrenia the blood levels of non-specific inflammation markers (WBS, CRP, ESR and Gra from the leukocyte formula) were high in the subpopulation of patients with the tendency towards normalization of inflammation parameters after a 4-week antipsychotic treatment. PMID- 26898033 TI - Importance of angle correction in transcranial color-coded duplex insonation of arteries at the base of the brain. AB - BACKGROUND/AIM: Transcranial color-coded duplex (TCCD) sonography allows visualization of the vessels being examined and measurement of the angle of insonation. The published literature suggests that blood vessels are insonated at the angle lower than 30 degrees, hence no correction for the angle is necessary. The aim of this study was to determine the availability of intracranial blood vessels for insonation, and the percentage of arteries and their segments which can be insonated at the angles lower than 30 degrees. METHODS: The study included 120 patients (mean age 51). For each of the segments the angle of insonation was registered based on TCCD vizualization, and hemodynamic parameters were measured. The angle of insonation was measured using combined B-mode and color Doppler vizualization, as the angle between the direction of the ultrasound beam and the axis of the shown arterial segment. RESULTS: The total success rate of insonation was 86.33% (1,554 out of 1,800). The mean angle of insonation value in all the examined arterial segments was 42 degrees. The insonation angle was higher than 30 degrees in about three quarters of the examined segments, especially in the A2 segment of the anterior cerebral artery (98%), the P1 segmet of the posterior cerebral artery (87%) and in the terminal internal carotid artery (83%). The A1 segment of the anterior cerebral artery showed the best insonation conditions with the angle of insonation lower than 30 degrees in 53% of the cases. CONCLUSION: The presented results of angles of insonation measurements for the anterior, middle and posterior cerebral arteries and their segments, as well as the terminal portion of the internal carotid artery clearly indicate that their average values in tested segments were very often higher than 30 degrees, which can cause an error in blood flow velocity measurement that cannot be ignored. The results confirm the necessity of correcting flow velocity values on the basis of the angle of insonation in TCCD sonography. PMID- 26898034 TI - Epidemics of the central nervous system infections caused by West Nile virus in the territory of the South Backa District, Vojvodina, Serbia. AB - BACKGROUND/AIM: West Nile virus (WNV) is a neurotropic RNA virus particle which belongs to the Flaviviidae family, genus Flavivirus. It is sustained in arthropods within the transmission cycle between the mosquitoes and birds. Most commonly (80% of cases) WNV infections are asymptomatic among people. Less than 1% of patients develop neuroinvasive forms of the disease--meningitis, encephalitis, or acute flaccid paralysis. The aim of the research was to determine most common clinical and laboratory manifestations, to emphazise the presence of comorbidities and outcomes of treatment among patients with WNV infection. METHODS: This retrospective study, which was conducted in the period from January 1, 2012 to December 31, 2013, evaluated 32 patients who were diagnosed with WNV infection based on clinical findings, laboratory, and serological tests. To assess statistical significance we used chi2, and t-test. RESULTS: The study involved 22 (69%) males and 10 (31%) females aged from 31 to 65 years. On admission, there were 16 (50%) febrile individuals, 27 (84.4%) with positive meningeal signs, 17 (53.2%) with pathological neurological signs, and 10 (31.3%) with consciousness disorders. WNV infection was confirmed by the method enzyme linked immuno sorbent assay (ELISA) in all the patients, while Reverse Transcription Polymerase Chain Reaction (RT-PCR) test was positive in 3 (30%) of the tested patients. Cardiovascular comorbidities dominated in 7 (21.9%) of the cases. Full recovery was accomplished in 87.5% of the cases. CONCLUSION: The results of our study show that the absence of meningeal signs and fever on the day 7 of hospital treatment are indicators of good course and prognosis of neuroinvasive forms of WNV infection. Comorbidities do not increase the risk of disease. ELISA test is a sovereign diagnostic method. In most cases, after the administered symptomatic therapy, the complete recovery of patients was achieved. PMID- 26898035 TI - Palliative embolization of renal tumors. AB - BACKGROUND/AIM: Palliative embolization of renal tumors is the method of choice in the treatment of advanced inoperable renal cell carcinoma in patients with hematuria and pain. Patients with small tumors in the remaining solitary kidney who refuse surgery are suitable for this type of therapy as well as patients with centrally located inoperable tumors. The prerequisite for successful capillary embolization is the closure of the main arterial trunk with metal spirals. METHODS: In the period from 2000 to 2010 we conducted 42 palliative embolizations. The average age of the patients was 75 years, including 26 men and 16 women. In 8 of the patients the intervention was repeated and in one with severe AV shunts embolization was performed 4 times. Embolization was performed with alcohol, Ivalon 150-250 um and with metal coils. RESULTS: No serious complications were observed during and after the intervention. Fourteen patient were still alive then and among the deceased patients the average survival time was 13.5 +/- 10.8 months with the range of 1 to 56 months. The minimal survival time was 1 month with a maximum survival time of 56 months. CONCLUSION: Our results are consistent with data in the literature. Survival in patients without metastases was longer than in those with metastases, as confirmed by the 14 of the patients from the study. An additional therapeutic safety in the treatment of small cancers is provided with a combination therapy of embolization and radiofrequency thermoablation. PMID- 26898036 TI - Structural features of arterial grafts important for surgical myocardial revascularization: Part II--Histology of the radial, inferior epigastric, and right gastroepiploic arteries. PMID- 26898037 TI - Rectosigmoid prolapse--A case report. AB - INTRODUCTION: Many factors have been indentified as a possible cause of rectal prolaps. Despite the fact that it is not a life- threating condition, its clinical presentation varies, and sometimes it can present as an emergency. We presented a patient with prolapse of an unusually large segment of the rectosigmoid colon caused by chronic constipation, as an incarcerated segment repaired surgically. CASE REPORT: A 62-year-old female patient was referred to the Emergency Department in bad condition with severe pain in the perianal region. On examination a complete rectal prolaps as well as a part of sigmoid colon were found. Macroscopically, the prolapsed segment appeared edematous, livid, with ulcerations. An attempt to manually reduce prolapse failed, therefore resection of 50 cm of sigmoid colon with rectopexy had to be performed. No complications occurred and the patient was without symptoms six months later. Colonoscopy did not reveal any abnormality. CONCLUSION: Although the preoperative management and preparation of the patient was limited, emergancy surgical intervention for such a case was the strategy of choice due to magnitude of the prolapsing segment. It provided a successful and permenant solution. PMID- 26898038 TI - Transplantation of infant kidneys--The surgical technique en bloc and transplant position variation: A case report. AB - INTRODUCTION: Due to the ever-present lack of kidney transplant grafts, more and more organs obtained from the so-called "marginal donors" group are accepted, which can provide suboptimal effect of transplantation, depending on their characteristics and/or implantation techniques. CASE REPORT: We presented a case with successful variation of kidney position with modified approach of kidney transplantation from an infant to an adult female patient with normal postoperative recovery. Urethral anastomosis was performed without antireflux procedure and this has not led to the development of reflux disease at an early stage. CONCLUSION: The position of a pair of kidneys proved to be satisfactory despite the growth of the kidney to the expected size and relatively small pelvis. There were no problems with venous stasis and kidney function from the very beginning was good. PMID- 26898039 TI - Application of modern computer-aided technologies in the production of individual bone graft: A case report. AB - INTRODUCTION: An autologous bone (bone derived from the patient himself) is considered to be a "golden standard" in the treatment of bone defects and partial atrophic alveolar ridge. However, large defects and bone losses are difficult to restore in this manner, because extraction of large amounts of autologous tissue can cause donor-site problems. Alternatively, data from computed tomographic (CT) scan can be used to shape a precise 3D homologous bone block using a computer aided design-computer-aided manufacturing (CAD-CAM) system. CASE REPORT: A 63 year old male patient referred to the Clinic of Dentistry of Vojvodina in Novi Sad, because of teeth loss in the right lateral region of the lower jaw. Clinical examination revealed a pronounced resorption of the residual ridge of the lower jaw in the aforementioned region, both horizontal and vertical. After clinical examination, the patient was referred for 3D cone beam (CB)CT scan that enables visualization of bony structures and accurate measurement of dimensions of the residual alveolar ridge. Considering the large extent of bone resorption, the required ridge augmentation was more than 3 mm in height and 2 mm in width along the length of some 2 cm, thus the use of granular material was excluded. After consulting prosthodontists and engineers from the Faculty of Technical Sciences in Novi Sad we decided to fabricate an individual (custom) bovine-derived bone graft designed according to the obtained-3D CBCT scan. CONCLUSION: Application of 3D CBCT images, computer-aided systems and software in manufacturing custom bone grafts represents the most recent method of guided bone regeneration. This method substantially reduces time of recovery and carries minimum risk of postoperative complications, yet the results fully satisfy the requirements of both the patient and the therapist. PMID- 26898040 TI - Unusual case of mixed form of femoroacetabular impingement combined with nonspecific synovitis of the hip joint in a young adult-- A case report. AB - INTRODUCTION: Minimal bone changes in the acetabulum and/or proximal femur, through mechanism known as femoroacetabular impingement, during flexion, adduction and internal rotation lead to early contact between femoral head-neck junction and acetabular brim, in anterosuperior region. Each additional pathological substrate which further decreases specified clearance provokes earlier onset of femoroacetabular impingement symptoms. CASE REPORT: We presented a 20-year-old male patient with groin pain, limping, positive impingement test, radiological signs of mixed form of femoroacetabular impingement and unrecognized chronic hypertrophic synovitis with earlier development of clinical hip symptoms than it has been expected. Open surgery of the left hip was done. Two years after the surgery, patient was asymptomatic, painless, and free of motion, with stable x-rays. CONCLUSION: Hypertrophic synovial tissue further reduces the distance between the femoral head-neck junction and the acetabulum, leading to the earlier onset of femoroacetabular impingement symptoms. Surgical treatment is the method of choice. PMID- 26898041 TI - Biological and Cultural Causes of Seasonality of Deaths in Historical Populations From Poland. AB - Seasonal fluctuations in mortality and their causes in the nineteenth century Polish rural populations: wealthy, agriculturally and economically advanced populations from Wielkopolska, and poor populations from Silesia and Galicia (southern Poland) were described. Data-sources included parish death registers from the Roman Catholic parish of Dziekanowice in the region of Wielkopolska, Prussian statistical yearbooks for the Pozna Province as well as information from previous publications regarding Silesia and Galicia. The 19th century patterns were compared with those in present-day Poland. The occurrence of seasonality of deaths was assessed with: the Chi-squared test, the Kolmogorov-Smirnov test, and the Autoregressive Integrated Moving Average Models (ARIMA). In all populations there was a winter maximum of the number of deaths, while the minimum occurred in early summer. In the poor populations of Silesia and Galicia another statistically significant increase in the incidence of deaths was observed in the early spring. In the rich and modern villages of Wielkopolska there was no spring increase in the number of deaths, however, in all populations of Wielkopolska, irrespective of a particular pattern, a secondary mortality peak occurred in the late summer and autumn. Statistical tests used in this study did not show any clear differences in the distribution of the seasonality of deaths between the populations of Wielkopolska on the one hand, and the populations from Galicia and Silesia, on the other hand. The statistical significance of differences was, however, evident between populations representing the two distinguished by secondary peaks death seasonality patterns. Seasonal death increase split the populations under study into two groups according to the criterion of wealth. PMID- 26898042 TI - Penetrating Arrow Injury--Causing the Death of an Early Medieval Woman from the Muzla-Cenkov Locality in Slovakia (9th-10th Century CE). AB - The osteological remains of a juvenile woman, 17-20 years, was discovered in grave number 23/88 at Muzla-Cenkov in the Nove Zamky district of Slovakia. Wound resulting from an iron arrowhead was located in her second lumbar vertebral body. Because of presence of the arrowhead in vertebral body and by the complete absence of any signs of healing processes, we conclude on perimortal injury which probably proved quickly extinguishing the life. DNA analysis was instituted for increased accuracy and reliability in establishing sex of this juvenile individual. An association with the old Hungarian troops who previously occupied this area was concluded, based on analytic evidence. PMID- 26898043 TI - The Legacy of Foundlings in Emilia-Romagna (Italy). AB - Between 1820 and 1929, in Iggio and in Tiola, rural parishes not too distant from the respective chief towns, a large number of marriages occurred between natives and former foundlings. The study of the distribution of surnames within the provinces of Emilia-Romagna (Italy) leads one to believe that the phenomenon was quite widespread in this region. This kind of marriage caused a direct gene flow from the town centres to the adjacent hilly areas. In general, however, the flow does not appear to have been so high as to change remarkably the genetic structure of the populations involved in the reception of the former foundlings, regardless that a percentage of them were taken to the hospitals of the towns from the countryside, and that many of those effectively born in the cities were children of people whose genetic pool did not differ substantially from that of the residents of the adjacent hilly zones. PMID- 26898044 TI - Can Our Fingers Alone Raise Us Up to the Sky? Analysis of the Digit Ratio Association with Success in Olympic Wrestling. AB - The aim of this study is to analyse the contribution of the second to fourth digit ratio (2D:4D) to success in wrestling. A total of 180 elite wrestlers who participated in the 2011 Spanish Wrestling Championship took part in this study (132 men, 23.6 +/- 6.1 years old; 48 women, 21.7 +/- 4.9 years old). Prior to competition, wrestlers were interviewed about their years of training experience and their hands were scanned. 2D:4D was calculated using computer-assisted image analysis. A multinomial logistic regression coefficient to calculate odd ratios (OR's) and 95% confidence intervals (CI's) were established to determine the contribution of digit ratio and training experience to success in Olympic wrestling. Additionally, mean and median analyses were calculated between males and females, and between successful and non-successful wrestlers in order to establish differences in 2D:4D and training experience between these groups. There were no differences between successful and non-successful wrestlers in 2D:4D (p=0.87 for right hand, and p=0.46 for left hand), whereas having high training experience supposed an increase up to 4.38,(1.70-11.01) times more likely to be successful. Our results suggest that 2D:4D fails in predicting wrestling success, whereas training background is a good predictor of competition prowess in highly trained wrestlers. PMID- 26898045 TI - Athletic Engagement and Athletic Identity in Top Croatian Sprint Runners. AB - The aim of the research was to determine construct validity and reliability for two questionnaires (Athlete Engagement Questionnaire-AEQ and Athletic Identity Measurement Scale-AIMS), applied on elite Croatian athletes-sprinters, as well as the correlations among the dimensions in these measuring instruments. Then, we have determined the differences in the dimensions of sport engagement and sport identity, according to gender, education level and winning medals on international competitions. A total of 71 elite athletes-sprinters (former and still active) are examined, from which 27 (38%) females and 44 (62%) males. The results of factor analyses revealed the existence of dimensions very similar as in the original instruments, which showed moderate to-high reliabilities. A small number of statistically significant correlations have been found between the dimensions of sport engagement and sport identity, mainly in male sprinter runners. Small number of statistically significant differences in the dimensions of sport engagement and sport identity have been found according to the gender, education level and winning medals on the international competitions. The most reasonable explanation of these differences could be given in terms of very similar characteristics of elite athletes on the same level of sport excellence. PMID- 26898046 TI - Developmental Study on Leg-to-Body Ratio Preferences. AB - Few studies have tested developmental differences in the perception of human body attractiveness and none have investigated development of Leg-to-Body Ratio (LBR) preferences. The aim of the current study was to determine whether preferences for LBR are largely innate and present among children in their early childhood, acquired in the course of socialization, and/or triggered by biological and hormonal changes. The study included 450 Polish men and women from Lower Silesia and Opole Province, Poland, whose ages ranged from 3 to 20 years. Participants were asked to choose which figurine they found the most attractive from a set of male and female figurines of various LBRs. We found that children below 8 years of age did not prefer any particular LBR and starting from about 9 years of age, preferences towards the legs of average length emerged. Importantly an LBR higher than the population average was not perceived as the most attractive until the age of 15 years. Therefore, we have empirically confirmed that LBR preferences change during develop ment. PMID- 26898047 TI - Impact of Body Composition and Vo2 Max on the Competitive Success in Top-Level Handball Players. AB - The purpose of the study was to determine the morphological and functional characteristics of 32 Serbian national U20 handball players (age 20.43 +/- 1.16 y; training experience 8.12 +/- 1.89 y) before European championship in Switzerland (2006) and to determinate their impact on competitive performance and outstanding success achieved. The results show that wing players differ from other players in morphological characteristics. Values for body height, weight, BMI, muscle mass and fat mass were significantly lower compared to the other playing positions. Extremely low values of maximal oxygen uptake (VO2 max) were measured in all players (ranged from 2.68 to 4.66 l x min(-1)). Pivots had the highest VO2 max in absolute values (3.76 l x min(-1)), and wing players in relative terms (40.83 ml x kg(-1) x min(-1)). Handball is characterized by high intensity intermittent play, followed by a number of walking breaks and quick substitutions. This makes possible to retain high playing intensity during whole match, because players can be given rest periods whenever needed. This will result in a high intensity game that does not necessarily require high VO2 max. Competitive success in modern top-level handball might be more reliant on optimal tactical preparation than on the body composition and VO2 max of an individual athlete. PMID- 26898048 TI - The Sensitiveness and Fulfillment of Psychological Needs: Medical, Health Care and Students. AB - As health was defined as a state of complete physical, mental, and social well being, and not merely an absence of disease or infirmity, the bio-psychosocial paradigm of health and illness attests that curing occurs when the science of medicine (the biomedical and pathos-physiological aspects of disease) and the art of medicine (the psychological, social, and interpersonal aspects of illness) merge into one unified holistic approach to patient care (Hojat, 2007). In this context the relationship between health care professionals and patients also become an indispensable tool in clinical situations to achieve better patient outcomes (Engel, 1990). In our pilot study in year 2009 we try to verify how are the medical students and students of health care (University of Maribor, Faculty of Medicine and Faculty of Health Care) prepared for their sensitive professional relationship in their future. Testing together 211 students (N=157 women, N=57 men), we compared the level of emotional empathy, altruistic love, values, and behaviorof 40 medical students, 118 students of health care and the group of 53 students of economics. Because of their professional choice, we expected that the medical and health care students would have higher empathy and altruism scores than the students of economics. Following the self-determination behavioral theory and its concept of autonomy support (Deci, Ryan, 2000), we anticipated also that the fulfilment of basic psychological needs could be important factor in everyday health care clinical practice. As the fulfilment of needs of autonomy, competence and relatedness could lead to increased autonomy supportive orientation in interactions with other subjects, and can be useful factor that prepare doctors or nurses for active participation in relationship with patients, we verified and compared the included groups also in this way. PMID- 26898049 TI - Intergenerational Contacts Influence Health Related Quality of Life (HRQL) and Subjective Well Being among Austrian Elderly. AB - Over the last century population ageing is a well described phenomenon all over the world. The dramatic absolute and relative increase in the population component of the elderly and the very old has influenced not only population structure but also the relationships within families, in particular between older parents and their adult children. The aim of the present study was to examine the impact of intergenerational contact frequency on health related quality of life among 62 men and 98 women ranging in age between 60 and 94 years. All participants of the study were healthy and lived independently in their private homes. Data concerning subjective well being and health related quality of life were collected by personal interviews based on structured questionnaires. Health related quality of life was tested by means of the WHOQOL-BREF. The main finding of this study is that the frequency of intergenerational contacts has a significant impact on health related quality of life. Contact frequency with grandchildren per month correlated significantly (p<0. 01) with all five domains of the WHOQOL-BREF. Contact frequency with sons and daughters per month correlated significantly (p<0.05) with the social and the global domain. According to Kruskall-Wallis tests and regression analyses with increasing intergenerational contacts health related quality of life increased significantly (p<0.01). According to these results a close and frequent contact to offspring is an important source for quality of life during old age. PMID- 26898051 TI - Intention to be Physically Active is Influenced by Physical Activity and Fitness, Sedentary Behaviours, and Life Satisfaction in Adolescents. AB - The aim of this study was to determine the association of levels of physical activity (PA), physical fitness (PF), sedentary lifestyle and life satisfaction with the intention to be physically active after secondary school graduation, in teenagers of both genders. A total of 1986 Spanish adolescents (12-16 years) participated in this cross-sectional study. PA, sedentary lifestyle, life satisfaction and intention to be physically active were assessed through validated questionnaires, and PF was evaluated objectively with the ALPHA battery tests. In both genders, adolescents who had significantly higher odds ratios (OR) of showing low intention to be physically active had low level of PA, cardiorespiratory fitness and muscular fitness in the lower body, and they were more sedentary in front of the computer. The girls that spent a lot of time watching TV and the boys with low life satisfaction also showed higher OR of having low intention to be physically active. PMID- 26898050 TI - Psychological Factors in Experience of Pain During Childbirth. AB - Pain during delivery is unique because it is accompanied by powerful emotions. Emotions that occur in women during labor and delivery are closely tied to upbringing and culture in which they were raised and consequently with the sensation of experienced pain. According to the Melzack-Wall Theory of Pain, general mood is directly related to the intensity and quality of pain and it is therefore justifiable to presuppose that certain psychosocial factors will be linked with the intensity and quality of pain experienced during childbirth. (Melzack et al., 1981). We endeavored to show the effect of psychosocial factors that influence the intensity and quality of labor pain. Data was collected in a sample of 176 parturient women who delivered without Cesarean sections or epidural anesthesia. The intensity and quality of pain were obtained through the administration of the McGill Pain Questionnaire-Short Form. Psychosocial factors included: number of births, presence of partner, self-evaluation of knowledge of physio-anatomical aspects of birth and the completion of a pregnancy course. Labor and delivery pain is of high intensity anl the quality of pain is most frequently characterized as smarting, cramping, exhausting, and sharp. The presence of a partner and the completion of a pregnancy course is exercised by a small number of parturients. Self-evaluation of preexisting knowledge of physio anatomical aspects of delivery is predictive of the affective component of intensity of childbirth pain. Psychosocial factors have been shown as significant for the intensity and quality of experienced childbirth pain. PMID- 26898052 TI - Changes of Respiratory Exchange Ratio in Children and Adolescents: A Longitudinal Study. AB - We conducted a longitudinal study to examine changes in the respiratory exchange ratio (RER) during progressively increasing body exertion in children and adolescents of female sex. In this analysis we only included 23 examinees for which we had all yearly measurements from examinee's age 9 years until 18 years of age. The data were analyzed according to the chronological and biological age. According to both criteria, the highest RER values were recorded at moments of maximum exertion and they did not increase with age. We found the highest RER values were in the year of the menarche. We interpret these results as related to the effect of estrogen. The beginning of sexual development involves a gradual increase in estrogen plasma concentrations. At one point serum levels of estrogen reach a level high, enough to allow for maximum RER values, i.e. causing the optimum anaerobic capacity of the examinee. This threshold estrogen value varies between individuals. PMID- 26898053 TI - Comparison of Home Advantage in College and Professional Team Sports in the United States. AB - Home advantage in seven American college team sports (baseball, basketball, football, hockey, lacrosse, soccer and women's basketball) was compared with professional leagues in the United States for the same sports and for the same time period. A total of 81,063 college games and 22,477 professional games were analyzed for the four seasons 2006-07 to 2009-10. There was a significant home advantage, as measured by home winning percentage, in all sports, both college and professional. The overall home advantage in college sports was significantly greater than in professional sports (p<0.015). The mean difference was 3.73 home winning percentage points, being greatest for baseball, basketball, and hockey (all p<0.001). Plausible explanations for these results include differences in college and professional competition in terms of familiarity with local conditions, referee bias, territoriality and psychological factors. However, the influence of travel fatigue was inconclusive. Only for soccer was the home advantage greater for professionals. This was the only sport where crowd size appeared to be having an effect. In addition the rules of college soccer allow more substitution and hence greater coach intervention than in professional soccer, a factor that could also be reducing home advantage. PMID- 26898054 TI - Differences among Tennis Players Aged 12, 14 And 16 Years in Certain Morphological Characteristics: A Croatian Prospective. AB - A sample of young tennis players aged 12, 14 and 16 in Croatia. Sixty (60) tennis players ranked on the scale of the Croatian Tennis Association were analyzed through differences in morphological characteristics, as identified by a standard laboratory diagnostic procedure in Sports-diagnostic Centre of the Faculty of Kinesiology at the University of Zagreb. Significant differences were obtained in most of the monitored measures for the assessment of the morphological characteristics but the most significant differences were reflected in the variables for assessment of longitudinal dimensionality of the skeleton and body mass and voluminosity of the body. The statistical significance was defined at p<0.05. These differences may lead to decelerating the development of important fitness abilities (i.e., coordination), but also highlights the importance for changing the official propositions for the category of players between the ages due to the significant differences in certain morphological characteristics among all age categories. This study indicates an importance of understand grow characteristics of young players in order to effectively define tennis players playing style. PMID- 26898055 TI - Subcutaneous Adipose Tissue Topography in Long-Term Enterally Fed Children and Healthy Controls. AB - In the context of enteral feeding in children the influence on growth and the question of fat resorption is of great interest. We, therefore, measured the thickness of subcutaneous body fat in a sample of long-term enterally fed toddlers and healthy controls. In 33 long-term enterally fed toddlers (10 girls, 23 boys) and 275 healthy controls (128 girls, 147 boys) subcutaneous body fat was measured by means) of the optical device Lipometer. All participants were divided into three age groups (infants, toddlers and children). The height (p=0. 014, 11.7 cm, -12.5%) and weight (p=0.012, -3.0 kg, -21.9%) of long-term enterally fed female toddlers were significantly lower than healthy controls, while male enterally fed toddlers had lower values in all anthropometric measures compared to healthy controls: height (p=0.003, -8.0 cm, -8.4%), weight (p<0.001, -3.5 kg, 24.8%), BMI (p=0.004, -1.3 BMI), Z-score BMI (p=0.001, -1.2 Z-score BMI), upper arm circumference (p<0.001, -1.6 cm, -10.1%) and waist circumference (p<0.001, 6.2 cm, -12.5%). Tube fed toddlers showed a similar body fat distribution when compared to healthy controls, but demonstrated significantly lower values of anthropometric measurements. The results indicate that long-term enterally fed children have ample fat stores but lack physical development. PMID- 26898056 TI - Caliper vs. Lipometer--Comparing Two Methods of Subcutaneous Body Fat Measurement by Bland-Altman Diagrams. AB - Skinfold Calipers are widely used to obtain subcutaneous adipose tissue thickness because of its non-invasive, simple and inexpensive technique. Nevertheless, Caliper skinfold thicknesses have the disadvantage of measuring compressed adipose tissue and double layers of skin, which might reduce the precision of these results. In contrast, the computerized optical device Lipometer was developed to permit a quick, precise and non-invasive determination of non compressed mono layers of subcutaneous adipose tissue thickness. In the present paper we investigate the hypothesis that Caliper skinfold thicknesses are significantly different from subcutaneous adipose tissue thicknesses in mm, which can be measured by Lipometer. Caliper and Lipometer results were obtained from 371 Estonian boys aged between 9.0 and 12.8 years. Measurements were performed at six different body sites: triceps, biceps, upper back, upper abdomen, hip and front thigh. Caliper measurements were systematically higher than Lipometer results in a range between 1.2 mm (hip) and 11.08 mm (front thigh). The limits of agreement analysis provided intervals from 7.5 mm (biceps) up to 30.14 mm (front thigh). Comparing Caliper and Lipometer results very low measurement agreement was found. The two methods provided very poor interchangeability. PMID- 26898057 TI - Performance Indicators of the Top Basketball Players: Relations with Several Variables. AB - The aim of this study was to determine the differences in performance indicators for top senior male basketball players, with respect to several independent variables: position in the team, total situation-related efficiency, age, playing experience and the time spent on the court within the game and during championship season. The final sample of participants was selected from all teams in A-1 Croatian men's basketball league. Significant differences have been found according to the players': position in the team, total situation-related efficiency, and in interactions of the position in the team / total situation related efficiency and minutes spent on the court in a game / playing experience. The differences in the situation-related efficiency between players have not been found according to the players' age and the number of games played. Further research can be directed towards deeper analysis of the influence of more complex differentiated variables playing experience and time spent on the court in a game on situation-related efficiency in basketball. PMID- 26898058 TI - The Prevalence of Spine Deformities and Flat Feet among 10-12 Year Old Children Who Train Basketball--Cross-Sectional Study. AB - The aim of this study is to estimate the prevalence of spine and feet deformities among children who are regularly involved in basketball trainings, as well as finding differences in the prevalence of those deformities between children of different gender and age. The study included a total of 64 children, of which 43 were boys and 21 were girls, ages 10-12. All subjects have been regularly participating in basketball trainings for at least one year. Postural disorder is defined as an irregularity in posture of the spine and feet, and it is assessed by visual methods from the front, side and rear side of the body. The prevalence of spinal deformities in our group was 53.13%. The boys had a significantly higher prevalence than girls, 65.1% compared to 28.57% (p=0.006). There was no significant difference in prevalence of spine deformities between children of different ages. The prevalence of feet deformities was 64.06%. There was a statistically significant difference between the sexes, where boys had a significantly greater prevalence of the feet deformities than girls, 83.7% compared to 23.81% (p=0.001). Flat feet were the most common in 10 year old children (85.71%). In conclusion, it can be said that despite regular participation in basketball training, subjects in this study have high prevalence of deformities; especially boys who stand out with the high prevalence of flat feet. PMID- 26898059 TI - Position-Related Differences in Selected Morphological Body Characteristics of Top-Level Female Handball Players. AB - The study aimed to establish the main morphological characteristics of Slovenian junior and senior female national handball team players. Morphological characteristics of various player subgroups (goalkeepers, wings, back players and pivots) were also determined so as to establish whether they had distinct profiles. The subjects were 87 handball players who were members of the Slovenian junior and senior female national teams in the period from 2003 to 2009. A standardised anthropometric protocol was used to assess the subjects' morphological characteristics. The measurements included 23 different anthropometric measures. First, basic statistical characteristics of anthropometric measures were obtained for all subjects together and then for each group separately. Somatotypes were determined using Heath-Carter's method. Endomorphic, mesomorphic and ectomorphic components were calculated by computer on the basis of formulas. In order to determine differences in the body composition and anthropometric data of the subjects playing in different positions, a one-way analysis of variance was employed. The results show that, on average, the wings differed the most from the other player groups in terms of their morphological body characteristics. The wings differed most prominently from the other player groups in terms of their morphological body parameters as they were significantly smaller and had a statistically significantly lower body mass than the other groups. In terms of transversal measures of the skeleton and the circumferences, the wings significantly differed mainly from the pivots and goalkeepers and less from the backs. The goalkeepers were the tallest, with high values of body mass and low values of transversal measures compared to P. Their skin folds were the most pronounced among all the groups on average and their share of subcutaneous fat in total body mass was the highest. Consequently, their endomorphic component of the somatotype was pronounced. Players in the Pivot position were significantly taller than the Wplayers but were not significantly different from G and B. They had high values of body mass which were significantly higher than that of W but did not differ significantly from the body mass values of B and G. The average values of their circumferences were the highest among all the player groups and the same is true for transversal measures of the skeleton. It is very interesting that, compared to the players in other playing positions, they achieved low values of subcutaneous fat. Their values of the somatotype revealed an endo-mesomorphic somatotype, with a pronounced mesomorphic component. Back players were tall and had the lowest share of subcutaneous fat of all the player groups. Significant differences were established mainly in terms of the structure of the lower extremities. The values of the somato-type characteristics were very balanced between all three components. The results of our study confirm that groups of handball players occupying different positions differed amongst themselves in terms of many measurements. This is a result of the specific requirements of handball play which are to be met by particular players. The tallest players should thus be oriented to back player positions. As regards pivots, the coaches must, besides body height, consider robustness. For goal-keepers, body height is very important; however, the robustness criteria are slightly lower. For wings, body height is not a decisive factor and smaller players can also occupy this position. Both of the above (also taking other criteria into account) facilitate coaches' decisions when orienting players into their playing positions. PMID- 26898060 TI - Functional Changes of P300 Values among Young Football Players as a Measure of a Cognitive Function. AB - Numerous studies have shown that evaluation of evoked potentials (EP) is an excellent estimation tool for a cognitive function. During daily practices footballers are exposed to headers that can leave mild head traumas. In this study, young footballers were examined, while the control group included their coevals who don't practice contact sports. Results of the study have shown that footballers have longer latency value of the P300 wave when target stimulus is presented on N1, N2 and P3, but not on P2. Also, they have longer latency values when non-target stimulus is presented. Amplitude values of target stimulus are not different, but footballers have lower amplitudes of non-target stimulus. This study suggests that EP evaluation method can be used to detect first and mild changes of the brain function. PMID- 26898061 TI - Dependence between Age at Menarche, Body Composition and Selected Somatic Indices. AB - The aim of this paper is to analyse age at menarche in Tanzanian girls for associations with body composition and selected somatic indices. The study included 97 girls (71 post-menarche and 26 pre-menarche). Measurements were taken of body height, body weight, waist and hip circumferences. Body composition was analysed for percentages of body H2O, fat, and muscle. The girls' nutritional status and body fat distribution were assessed using the following somatic indices: BMI, WHR (Waist-to-Hip Ratio) and WHtR (Waist-to-Height Ratio). For the post-menarcheal group N=71, backward stepwise multiple regression analysis was performed. Average age at menarche calculated using the recall method for N=71 was X=14.29 years, calendar age X=15.92 years. More than half (57.69%) of the girls in the pre-menarche group had not reached the body weight of 48kg, whereas in the post-menarche group they accounted for 32.39%. As many as 97.18% of the post-menarche girls had body fat content of 22%, compared to 88.46% in the pre menarche group. In terms of BMI, 74.65% of post-menarche girls had healthy weight, compared to 73.08% in the pre-menarche group. There were no significant differences in WHR or WHtR, which may indicate similar fat distribution in girls prior to and after menarche. The analysis showed that the onset of menstruation is not strictly dependent on reaching a critical point in body weight or body composition. PMID- 26898062 TI - Understanding Basic Temporal Relations in Primary School Pupils with Hearing Impairments. AB - Time can be observed as a subjective, as well as an objective phenomenon which is a component of our life, and due to its communicational needs, it is standardized by temporal signs and symbols. The aim of this study was to determine the understanding of basic temporal relations of pupils with hearing impairments. We assumed that the knowledge of basic time relations is a precondition for the acquisition of knowledge that is connected with the understanding of the syllabus in regular school programs. Three groups of pupils have been examined: pupils with hearing impairments who attend the primary school of SUVAG Polyclinic under special condition, integrated hearing impaired pupils with minor additional difficulties who attend regular primary schools in Zagreb with a prolonged expert procedure and pupils of the control group. The subjects have been examined with a measuring instrument constructed by the expert team of the Polyclinic Suvag. Twenty nine subjects have been questioned, chronologically aged between 10 and 12. PMID- 26898063 TI - The Comparison of Malocclusion Prevalence Between Children with Cerebral Palsy and Healthy Children. AB - This study sets out to examine the prevalence of malocclusion and habits in a group of children with cerebral palsy and to compare it with a control group of healthy children. The presence of an anterior open bite was statistically significantly higher in the cerebral palsied group. The presence of aposterior crossbite was not significantly different between the examined groups, as was the case for a lingual crossbite. The occurrence of visceral swallowing, incompetent lips and oral respiration was significantly higher in the cerebral palsied group. The current study cannot satisfactorily sustain the issue of a higher prevalence of posterior and lingual crossbite in children with cerebral palsy because of no significant differences between groups, but it certainly can for an anterior openbite. The present study also adds to the evidence that there is an increased prevalence of oral breathing, visceral swallowing and lip incompetence in children with cerebral palsy. PMID- 26898064 TI - Additive Manufacturing of Medical Models--Applications in Rhinology. AB - In the paper we are introducing guidelines and suggestions for use of 3D image processing SW in head pathology diagnostic and procedures for obtaining physical medical model by additive manufacturing/rapid prototyping techniques, bearing in mind the improvement of surgery performance, its maximum security and faster postoperative recovery of patients. This approach has been verified in two case reports. In the treatment we used intelligent classifier-schemes for abnormal patterns using computer-based system for 3D-virtual and endoscopic assistance in rhinology, with appropriate visualization of anatomy and pathology within the nose, paranasal sinuses, and scull base area. PMID- 26898065 TI - The Influence of Changes in Size and Proportion of Selected Facial Features (Eyes, Nose, Mouth) on Assessment of Similarity between Female Faces. AB - The project aimed at finding the answers to the following two questions: to what extent does a change in size, height or width of the selected facial features influence the assessment of likeness between an original female composite portrait and a modified one? And how does the sex of the person who judges the images have an impact on the perception of likeness of facial features? The first stage of the project consisted of creating the image of the averaged female faces. Then the basic facial features like eyes, nose and mouth were cut out of the averaged face and each of these features was transformed in three ways: its size was changed by reduction or enlargement, its height was modified through reduction or enlargement of the above-mentioned features and its width was altered through widening or narrowing. In each out of six feature alternation methods, intensity of modification reached up to 20% of the original size with changes every 2%. The features altered in such a way were again stuck onto the original faces and retouched. The third stage consisted of the assessment, performed by the judges of both sexes, of the extent of likeness between the averaged composite portrait (without any changes) and the modified portraits. The results indicate that there are significant differences in the assessment of likeness of the portraits with some features modified to the original ones. The images with changes in the size and height of the nose received the lowest scores on the likeness scale, which indicates that these changes were perceived by the subjects as the most important. The photos with changes in the height of lip vermillion thickness (the lip height), lip width and the height and width of eye slit, in turn, received high scores of likeness, in spite of big changes, which signifies that these modifications were perceived as less important when compared to the other features investigated. PMID- 26898066 TI - Patients' Reactions to Local Anaesthetic Application Devices in Paediatric Dentistry. AB - Local anaesthesia is the most common medium for pain control in most dental treatments. Physical appearance of syringe itself can be considered as a provoking factor for the emergence of dental fear and anxiety (DFA). In this research the patient reactions to local anaesthesia application devices, as one of the main causes for DFA emergence, were inquired. The sample comprised of 120 patients, divided in three age groups, formed of 40 patients aged 8, 12 and 15 years. DFA prevalence was quantified by Children Fear Survey Schedule-Dental Subscale (CFSS-DS). Three different syringes were offered to the patients. Reasons for choosing one of the syringes were detected. Patients assigned statistically highest rank to plastic syringe. Boys chose metal and intraligamental syringe statistically more often than girls. Patients with higher CFSS-DS scores chose metal syringe as last option. None of the reasons for selection was dominant, except pain that could be caused by usage of any of the three syringes. A large number of patients did not mention any of the reasons for choosing particular syringes. Plastic syringe represented the most acceptable device for local anaesthetic application to our patients. Patients often linked pain with dental syringes. PMID- 26898067 TI - Biopsy Quantitative Patohistology and Seral Values of Prostate Specific Antigen Alpha (1) Antichymotrypsine Complex in Prediction of Adverse Pathology Findings after Radical Prostatectomy. AB - In this prospective study we examined the utility of parameters obtained on prostate needle biopsy and prostate specific antigen-alpha(1)-antichymotripsine complex (PSA-ACT) to predict adverse pathologic findings after radical prostatectomy. 45 consecutive patients assigned for radical prostatectomy due to clinically localized prostate cancer were included in the study. Prostate biopsy parameters such as number of positive cores, the greatest percentage of tumor in the positive cores, Gleason score, perineural invasion, unilaterality or bilaterality of the tumor were recorded. PSA-ACT was determined using sandwich immunoassay chemiluminiscent method (Bayer, Tarrytown, New York). We analyzed relationship of preoperative PSA, PSA-ACTand quantitative biopsy parameters with final pathology after prostatectomy. Adverse findings were considered when extracapsular extension of cancer (pT3) was noted. Postoperatively, 29 (64.4%) patients were diagnosed with pT2 disease and 16 (35.6%) with pT3 disease. There was a significant difference in localized vs. locally advanced disease in number of positive biopsy cores (p<0.001), greatest percentage of tumor in the core (p=0.008), localization of the tumor (p=0.003) and perineural invasion (p=0.004). Logistic regression was used to develop a model on the multivariate level. It included number of positive cores and PSA-ACT and was significant on our cohort with the reliability of 82.22%. The combination of PSA-ACT and a large scale of biopsy parameters could be used in prediction of adverse pathologic findings after radical prostatectomy. Clinical decisions and patients counselling could be influenced by these predictors but further confirmation on a larger population is necessary. PMID- 26898068 TI - Impact of Positive Surgical Margins after Radical Prostatectomy on Disease Progression and Adjuvant Treatment in Pathologically Localized Prostate Cancer. AB - The aim of our study was to evaluate the impact of margin positivity in clinically and pathologically localized prostate cancer (pT2) after radical prostatectomy on biochemical recurrence and time to adjuvant treatment. We analyzed data from 371 patients who underwent radical prostatectomy. At the mean follow up of 36 (25-54) months, impact of margin positivity in pT2 patients on prostate specific antigen (PSA) recurrence and time to introduction of adjuvant treatment was noted. Out of 371 radical prostatectomies there were 277 (74.6%) pT2 and 94 (25.4%) pT3 (locally advanced) prostate cancers. Mean age was 67.6 years, mean Gleason score 6.78, mean preoperative PSA 11.45 ng/mL. Out of 277 pT2 pts., 233 (84%) had negative (SM-) and 44 (16%) positive surgical margins (SM+). Only 3% of SM- pts. had biochemical relapse (BCR). Among pT2 patients with SM+, 18 (41%) had BCR while 26 were free of recurrence at 3 years follow up. Positive surgical margins had an adverse impact on biochemical progression free survival (3% SM- vs. 41% SM+; p<0.001). No difference was found in age, preoperative PSA, Gleason score or follow up between BCR-SM+ and BCR+SM+ patients. Mean time to PSA recurrence in surgical margin positive pT2 patients was 15.7 months. Surgical margin status pT2 disease has an impact on biochemical progression but only 41% of margine positive patients show biochemical recurrence at 3 yr follow up. Not all SM+ patients need to receive treatment after radical prostatectomy. Longer follow up should be awaited to see the impact on overall survival in this group of patients. PMID- 26898069 TI - Adjuvant Cancer Biotherapy by Viscum Album Extract Isorel: Overview of Evidence Based Medicine Findings. AB - Within the integrative medicine one of the most frequently used adjuvant cancer biotherapies is based on aqueous mistletoe (Viscum album) extracts. Tumor growth inhibition, stimulation of host immune response and improvement of the quality of life are the positive effects of mistletoe therapy described in several preclinical and clinical studies. However, cumulative results of the evidence based medicine findings on such treatments are rarely given. Therefore, this paper evaluates the evidence based findings describing effects of the Viscum album extract Isorel in cancer therapy with respect to the type of therapy, stage and type of illness. This study presents cumulated data for 74 patients with different types and stages of cancer treated by Viscum album extract as adjuvant treatment to different conventional therapies, mostly combined surgery and radiotherapy. The biotherapy effectiveness was evaluated according to the outcome as (1) no major therapeutic improvement (15% of patients), (2) prevention of tumor recurrence (47% of patients) and (3) regression of cancer (38% of patients). Notably, there was no obvious health worsening during the follow up period at all. Thus, the results obtained for conventional anticancer therapies combined with adjuvant biotherapy based on Viscum album extract seem to be beneficial for the majority of cancer patients (85%) without serious side effects. PMID- 26898070 TI - Validation of Epstein Biopsy Criteria for Insignificant Prostate Cancer in Contemporary Cohort of Croatian Patients. AB - Only few reports validated contemporary Epstein criteria for insignificant prostate cancer, and only one being from Europe. Patients with insignificant prostate cancer should be offered active surveillance and spared radical treatment. In our study we tested Epstein biopsy criteria for predicting unfavorable final pathology and biochemical relapse in low risk prostate cancer patients, who were eligible for active surveillance but where treated with radical prostatectomy. Between January 2003 and January 2008, 586 patients were subjected to radical prostatectomy in our institution. Among them, 106 where eligible for active surveillance according to Epstein biopsy criteria for insignificant prostate cancer. We analyzed the presence of adverse pathological findings in the final pathohistological specimen after radical prostatectomy which excludes low risk disease. Adverse pathohistological findings were noted in 41 (38.6%) patients, who could have been offered active surveillance. During the follow up of 48 (12-72) months, biochemical relapse was noted in 6 (5.6%) patients. Although active surveillance is becoming more popular because of the long natural course of prostate cancer and fear of overtreatment of patients with indolent course of disease, both doctors and patients must be aware of potentially significant disease in this group and limitations of current preoperative criteria defining low risk patients. PMID- 26898071 TI - Does Cytological Laboratory Holds the Responsibility for the Low Sensitivity of the PAP Test in Detecting Endometrial Cancer? AB - Endometrial cancer is the most common gynecological cancer but there is no economically justified screening method. Although we can detect endometrial cells in the sample using PAP test, many studies show low sensitivity and positive predictive value of PAP test for the diagnosis of endometrial cancer. The goal of this research was to determine significance of PAP test for the diagnostics of endometrial carcinoma. Sensitivity and specificity were analyzed with statistical parameters. VCE (vaginal, cervical, endocervical) smears of patients with histologically proven endometrial carcinoma were re-examined in order to determine the proportion of false negative results for endometrial cancer cells in the VCE samples. Study group consisted of all consecutive patients with PAP test performed at the Department of Clinical Cytology of the University Hospital Center Osijek from 2002 until the end of 2014. There was one inclusion criteria: subsequent hysterectomy or curettage within the six month after the PAP test, regardless of histological finding. From a total of 263 patients with previous PAP test and histologically proven endometrial cancer, endometrial cancer was cytologicaly diagnosed in 24.7% (including suspicious and positive findings), while 66.2% patients had normal cytological findings. The diagnostic value of PAP test in detection of endometrial cancer was statistically revealed with 25% sensitivity and 99% specificity. To determine false negative rate VCE samples were reviewed for patients with histologically proven endometrial cancer and negative VCE findings. There were a total of five negative results. In one case revision did not changed the original negative diagnosis, but benign endometrial cells, a lot of blood and inadequate cytohormonal status were found. In three out of four reviewed samples there were missed cells of endometrial adenocarcinoma. Review of remaining VCE sample upgraded the diagnosis from negative to suspicious for endometrial cancer. Proportion of error in the detection of endometrial cancer using cytological findings was 3.4% (true false negatives). Negative rate of the cytological findings in the detection of endometrial cancer was 66.2%. PAP test is not a suitable method for detection of endometrial carcinoma due to low sensitivity (25%). The main cause of negative findings in PAP test was lack of diagnostic cells in the sample. PMID- 26898072 TI - Influence of Diastolic Blood Pressure on Glaucoma Progression in Glaucoma Patients with Systemic Hypertension. AB - The aim of this study is to determine relationship between glaucoma progression and diastolic blood pressure. It was conducted on 64 glaucoma patients at the Department of Ophthalmology of Clinical Hospital Centre Zagreb in three years period. The patients were on anti glaucoma therapy and had mean intraocular pressure values under 20 mmHg. At the same time they were on antihypertensive drug therapy. Patients were classified according Glaucoma Staging System based on the perimetric indices mean deviation (MD) and Pattern Standard Deviation into stage 2-4 (moderate glaucoma) at baseline. Rate of visual field progression was calculated in db/year for MD in the last three visits. Patients were divided in 3 groups according to progression--stabile, moderate and progressive. There was no statistically significant difference between 3 groups in terms of intraocular pressure values at baseline and in follow up period. After reviewing their blood pressure, the progressive group showed a significantly lower diastolic blood pressure compared to both stable group and the group with moderate progression. There was no statistical difference between the group with moderate progression and the stable group in terms of diastolic blood pressure. Results suggest that greater risk of glaucoma progression is connected with lower diastolic blood pressure. Diastolic pressure values could be important as one of the risk factors for progression in glaucoma patients with controlled intraocular pressure values. PMID- 26898073 TI - Incidence of Stroke and Transient Ischemic Attack in Croatia: A Population Based Study. AB - The aim of this population based neuroepidemiological study was to establish the real incidence rates of acute cerebrovascular disease (CVD): stroke and transient ischemic attack (TIA) in the Republic of Croatia. Multicentric study included 89 501 persons of all ages in four regional centres in Croatia: Zagreb, Osijek + Slavonski Brod, Rijeka and Split. The following incidence rates of stroke, expressed at population of 100 000, have been established: Zagreb 290.52, Osijek + Slavonski Brod 302.14, Rijeka 219.65, Split 195.82. Incidence rate of stroke for the Republic of Croatia is 251.39. The following incidence rates of TIA, expressed at population of 100,000, have been established: Zagreb 87.15, Osijek + Slavonski Brod 156.53, Rijeka 90.11, Split 59.10. Incidence rate of TIA for the Republic of Croatia is 100.55. In the continental part of Croatia (Zagreb, Osijek + Slavonski Brod) incidence rate of stroke is higher by 45%, while incidence rate of TIA is higher by 82% than in the coastal part of Croatia, probably due to different lifestyle and environmental factors. The study has shown relatively high incidence rates of acute CVD (stroke and TIA) in the Republic of Croatia, which proves that CVD are a great public health problem. PMID- 26898074 TI - Sexually Transmitted Diseases as a Risk for Acquiring HIV Infection among the Population of Men Who Have Sex with Men--A Case-Control Study. AB - At the beginning of the 1980-ies, HIV infection and AIDS were described for the first time, this among the population of men who have sex with other men. Nearly thirty years later, the MSM population is still a population under heightened risk for acquiring HIV infection and other sexually transmitted diseases. This study investigates sexually transmitted diseases as a risk for HIV infection. A total of 296 men who have sex with men (MSM) were included in this case control study. Differences among the frequencies of sexually transmitted diseases among the MSM of HIV positive and HIV negative status were tested. The history of HIV positive more often states falling ill with sexually transmitted diseases than this was the case before they became HIV positive, unlike those MSM who are not HIV infected (45.9%:11.1% that is OR 6.79, 95% CI 3.49-13.19). Hepatitis B infection is more frequent in HIV positive MSM (11.5%:1.9%; OR 6.58, 95% CI 1.86 23.3). The frequency of gonorrhea in case history of HIV positive MSM is significantly higher than in the HIV negative group (11.5%:3.8%, OR 3.24, 95% CI 1.13-9.34). In the group of HIV positive MSM, unlike the HIV negative group, syphilis (14.8:1.0%, OR 1774, 95% CI 3.43-122.87) and genital herpes (8.2%:0.5%, OR 18.39, 95% CI 2.03-424.7) are more frequent. The results of this study will be used in future preventive activities focused on the population of MSM, as a population under particular risk for acquiring sexually transmitted infections. PMID- 26898075 TI - Creatinine Clearance and Estimated Glomerular Filtration Rate--When are they Interchangeable. AB - Study goal was to examine which of glomerular rate equations is most suitable for prediction of creatinine clearance (CrCl). Using a retrospective review of data from 500 hospital patients we calculated glomerular filtration rate according to Cockcroft-Gault equation (C-G), Modification of Diet in Renal Disease Study equation (MDRD) and Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI). We determined if results of these equations were compatible with CrCl, and does stage of kidney disease, body-mass index (BMI), diabetes or old age have an impact on their ability to predict creatinine clearance. All of the equations showed high correlations with CrCl, regardless of diabetes, overweight or old age. There was no significant difference (p<0.05) between diagnostic accuracy when comparing ROC plots for MDRD and CKD-EPIat CrCl cut offs of 60 ml/min/1.73 m2 and 90 ml/min/1.73 m2 when analyzing data for all patients, older patients (>65 years) and diabetics. The percentage of overweight patients (BMI > or = 25) in patients with normal CrCl and decreased GFR was 64.81% for C-G, 92.04% for MDRD and 91.36% for CKD-EPI. Large number of overweight patients with normal CrCl and decreased GFR would indicate that CrCl overestimates GFR in overweight patients. The simple correction in CrCl for obese subjects is purposed. Passing Bablok regression showed agreement between CrCl and MDRD and CrCl and CKD-EPI only in cases of severely decreased GFR (G4 and G5 stage of chronic kidney disease). Only in these stages of chronic kidney disease can CrCl and MDRD or CrCl and CKD-EPI be used simultaneously. PMID- 26898076 TI - Expression of CD133 and CD117 in 64 Serous Ovarian Cancer Cases. AB - The cancer stem cells (CSCs) represent a minority of tumor cells that are able to proliferate and self-renew and might be responsible for tumor initiation and maintenance. The CD133 and CD117 are the most commonly used markers for the putative CSCs, especially for the ovarian CSCs, but its clinical significance remains uncertain. The aim of this study was to compare the immunohistochemical expression of CD133 and CD117 in 64 primary ovarian high grade serous carcinoma and peritoneal metastasis, and to examine their potential clinical role. CD133 expression was mainly seen in the apical/endoluminal cell surface of tumor cells and was found in 61% of the carcinoma samples and 41% of the metastasis. The median of CD133 positive cells in tumors was 1 (0.1-7)%, and in metastases was 0.6 (0.1-6)%. CD117 expression appeared as a cytoplasmic and/or membranous stain and was found in 81% of the carcinoma samples and 77% of the metastasis. The median of CD117 positive cells in tumors was 1 (0.1-8)%, and in metastases was 0.1 (0.1-7)%. Multivariate analysis has shown that patients with high CD133 expression in tumor cells have significantly shorter disease free survival and overall survival (p=0.025 and p=0.014, respectively). Patients with high CD117 expression in tumor cells have significantly shorter disease free survival (p=0.031). Cox's proportional hazards model identified expression of CD133 protein in tumor as an independent prognostic factor. Our study indicates that the immunohistochemical assessment of CD133 and CD117 expression may have potential clinical value in predicting disease progression and prognosis in the high grade serous ovarian cancer. CD133 proved to be an independent prognostic factor in the high grade serous ovarian cancer patients. PMID- 26898077 TI - FOXP1 Expression in Normal and Neoplastic Erythroid and Myeloid Cells. AB - FOXP1 protein was firstly analyzed in normal tissues, and afterwards in different tumor tissues, mainly carcinoma and lymphoma. In B-cell malignancies, its role was well explored; its expression was shown to be connected with disease prognosis in certain B-non Hodgkin lymphomas. In this study, 16 bone marrow trephine samples from patients with no hematopoietic malignancies and 10 samples from peripheral blood of healthy individuals were immunostained with anti-FOXP1 antibody. Positive cells in bone marrows were not only lymphocytes, but also cells that are immunohistochemically positive for glycophorin C or myeloperoxidase. Peripheral blood samples showed no other positive cells, but small round lymphocytes. Additionally 60 samples from patients with myeloid lineage neoplasms were analyzed. 25 samples from patients with myelodysplastic syndrome (MDS) and 35 patients with myeloproliferative disease (MPD) were double immunostained with anti-FOXP1/anti-glycophorin C and anti-FOXP1/anti myeloperoxidase antibodies. FOXP1 was found to be expressed in 22 cases of MDS and in none of MPD cases. Its expression in MDS was observed mostly in myeloperoxidase positive cells in contrast to gylcophorin C positive cells. Only two cases revealed both myeloperoxidase positive cells and gylcophorin C positive cells expressing FOXP1 transcription factor. Our results show that FOXP1 is present in normal cells of erythroid and myeloid linages and thus suggest its possible role in development of all hematopoetic cells as well as possible involvement in neoplasm development of myeloid disorders. PMID- 26898078 TI - Knowledge About Head and Neck Cancer in the Population of Vojvodina: A Comparative Study. AB - In 2009, the Institute of Oncology of Vojvodina reported the total of 553 newly registered patients with head and neck cancer (HNC) in the Province of Vojvodina, with a lethal outcome in 332 HNC patients. These facts impose the need of investigating the health education of the general population and proposing possible prevention measures. The present prospective study included 200 subjects classified into two groups. Group 1 (100 subjects) consisted of randomly selected adults from urban and rural regions of Vojvodina. Group II (100 subjects) included the adults from the same regions affected by HNC. All subjects answered the anonymous questionnaire which complied with the standards of a similar European Union research project "About Face". The results showed that 96% of the subjects from the Group II and only 77% of the subjects from the Group I were familiar with the term "head and neck cancer" what represented a significant difference. The results from Vojvodina were significantly better than those from the European study (23%). Most subjects were informed about HNC through television programs (60%), hospital leaflets (41%) or internet (37%). Both the patients and the citizens of Vojvodina were better informed about the most common localizations of HNC-pharynx and larynx, but less informed about other HNC localizations than the citizens of seven European countries. The citizens and the HNC patients from Vojvodina were equally well informed about some risk factors (e.g., smoking, alcoholism, aging and sun exposure) as the citizens in Europe. Both the patients and the general population of Vojvodina are mostly worried about the consequences/side effects of the applied surgical treatment. The obtained results may be a good starting point in the prevention and early detection of HNC in Vojvodina. PMID- 26898079 TI - Palmar Creases: Classification, Reliability and Relationships to Fetal Alcohol Spectrum Disorders (FASD). AB - A normal human palm contains 3 major creases: the distal transverse crease; the proximal transverse crease; and the thenar crease. Because permanent crease patterns are thought to be laid down during the first trimester, researchers have speculated that deviations in crease patterns could be indicative of insults during fetal development. The purpose of this study was twofold: (1) to compare the efficacy and reliability of two coding methods, the first (M1) classifying both "simiana" and Sydney line variants and the second (M2) counting the total number of crease points of origin on the radial border of the hand; and (2) to ascertain the relationship between palmar crease patterns and fetal alcohol spectrum disorders (FASD). Bilateral palm prints were taken using the carbon paper and tape method from 237 individuals diagnosed with FASD and 190 unexposed controls. All prints were coded for crease variants under M1 and M2. Additionally, a random sample of 98 matched (right and left) prints was selected from the controls to determine the reliabilities of M1 and M2. For this analysis, each palm was read twice, at different times, by two readers. Intra-observer Kappa coefficients were similar under both methods, ranging from 0.804-0.910. Inter-observer Kappa coefficients ranged from 0.582-0.623 under M1 and from 0.647 0.757 under M2. Using data from the entire sample of 427 prints and controlling for sex and ethnicity (white v. non-white), no relationship was found between palmar crease variants and FASD. Our results suggest that palmar creases can be classified reliably, but palmar crease patterns may not be affected by fetal alcohol exposure. PMID- 26898080 TI - The Role of Tonsillectomy in the Prevention of Helicobacter Pylori Infection. AB - The incidence of Helicobacter pylori infection varies globally and depends on the socioeconomic situation of a location. In the territory of Croatia, the incidence rate among the populace is 40-50% in persons with normal gastroscopic findings, whereas it is increased in persons with the pathohistological finding of the ulcus disease. This study examines the potential preventive role of tonsillectomy with regard to H. pylori infection in later stages of life. The survey was conducted on a sample of 115 examinees (63 male, 52 female), aged between 19 and 86. The survey included examinees that underwent esophagogastroscopy at the Institute of Gastroenterology of the University Hospital Centre Osijek based on indication by a gastroenterology specialist. The survey has shown that of the total of 115 examinees, 28 of them had been tonsillectomised, and 87 had not been tonsillectomised. In the examinees who had not been subjected to tonsillectomy, positive H. pylori result was found in 63.2%, and 53.6% of those who had been tonsillectomised at a young age were positive to H.pylori. The results have shown that H. pylori infection was equally represented in all age groups, and the rate varies at 52.9-64.8%. Hence, the final conclusion was reached that tonsillectomy has no preventive role with regard to H.pylori infection. PMID- 26898081 TI - Relationship between Age and Thickness of Carotid Arteries in a Population without Risk Factors for Atherosclerosis. AB - The intima-media thickness (IMT) of carotid arteries is a marker of subclinical atherosclerosis associated with risk factors for atherosclerosis and a predictor of vascular disease. The aim of the research was to determine the correlation of IMT and age, and above normal IMT values in healthy adults in Slavonia (eastern Croatia). The study included 275 subjects of both sexes, aged between 20 and 79, who had no clinical manifestations of vascular disease or presence of major risk factors for atherosclerosis (hypertension, hypercholesterolemia, diabetes mellitus, cigarette smoking). Ultrasonic measurement of IMT in the B-mode was performed on far walls of the carotid arteries on both sides at three locations (common and internal carotid artery, carotid bifurcation). At all three sites of measurement a high correlation between the IMT values and age was found in both sexes, including the maximum for IMT of carotid bifurcation (men r=0.92, women 0.91). Upper normal values (75th percentile) IMT of common carotid arteries were determined for the ten year age groups. It is the same for both men and women in age groups both 20-29 and 30-39 (0.41, 0.46 mm). On the other hand, in age groups 40-49, 50-59, 60-69 and 70-79 upper normal values for men are 0.57, 0.62, 0.77 and 0.96 mm, and for women 0.50, 0.57, 0.71 and 0.81 mm. Our study in healthy adults in Slavonia (eastern Croatia) established a clear con- nection between carotid IMT and age, which implies a need for taking the age as an essential factor into account when conducting researches that involve the IMT. PMID- 26898082 TI - Low-dose Computed Tomography in a Pregnant Woman with a Ruptured Pseudoaneurysm of the Abdominal Aorta. AB - Imaging the pregnant patient presents a unique challenge to radiologist due to the risk of radiation to the conceptus (embryo/fetus). A rare case of a successfully recognized and treated pseudoaneurysm (PA) of the abdominal aorta is to be presented. The pseudoaneurysm occurred in the third trimester and had a favorable outcome for the mother and the baby. Emergent abdominal ultrasound (US) is the first modality in diagnostic algorithm for the rupture of aortic aneurysm in a pregnant woman. It provides the most rapid diagnostic information, although intestinal gas and abdominal tenderness may limit its accuracy. To confirm the findings, magnetic resonance angiography (MRA) or CT angiography (CTA) can be used. In our case, the diagnosis was established using a color Doppler ultrasonography of the abdomen and was later confirmed by a low dose CT scan of the abdominal aorta. MRA in such cases have some disadvantages. At many health centers, the monitoring of patients with acute ruptures is more difficult in the MR suite than at the CT scanner. MRA angiographic images are also subject to degradation by multiple artifacts and the visualization of the distal vasculature is suboptimal and inferior to the one done by CTA. Due to fetal movements, a small quantity of fresh blood can be overlooked by MR. MRA is often not available on a 24-hours basis, and the time required for making a diagnosis can preclude the use of MRA in an unstable patient. For this reason, we used a low dose CTA protocol to confirm the diagnosis. Low dose scanning protocols in CT can obtain sufficient diagnostic information while reducing the risk of radiation. A particular focus is put on the outline of new concepts for dose management and optimization. We used new approaches based on tube current modulation. The birth was induced by an urgent Caesarean section followed by a resection of a pseudoaneurysm and a reconstruction of the aorta with an end-to-end vascular prosthesis. PMID- 26898083 TI - Dermoscopy and Early Melanoma. AB - The lack of effective therapies for patients with advanced melanoma establishes an early recognition as the aim of clinical and dermoscopic examination, which is the most important factor for improving patient survival and decreases the treatment and management costs. Melanoma in situ is the earliest stage of melanoma. The features of early melanomas, especially in those lesions smaller than 3mm, can be very subtle clinically, dermoscopically and pathohistologically, and it is often impossible to discriminate between a melanoma and nevus. Clinically, de novo melanomas are small brown to black macula with an irregular outline. In melanomas developing in a nevus, there is an asymmetry of the lesion with marked change in color and/or shape of the pre-existing nevus. Dermoscopically, early stages of melanoma show the same global features as thicker melanomas, but in a more subtle way. Asymmetry is the most important parameter; multiple colors are rare. Significant local melanoma-specific criteria, especially when present at the periphery, are irregular pigment network, irregular streaks, and irregular dots/globules, while blue-white structures are rarely found. PMID- 26898084 TI - Reliability of the ATD Angle in Dermatoglyphic Analysis. AB - The "ATD" angle is a dermatoglyphic trait formed by drawing lines between the triradii below the first and last digits and the most proximal triradius on the hypothenar region of the palm. This trait has been widely used in dermatoglyphic studies, but several researchers have questioned its utility, specifically whether or not it can be measured reliably. The purpose of this research was to examine the measurement reliability of this trait. Finger and palm prints were taken using the carbon paper and tape method from the right and left hands of 100 individuals. Each "ATD" angle was read twice, at different times, by Reader A, using a goniometer and a magnifying glass, and three times by a Reader B, using Adobe Photoshop. Inter-class correlation coefficients were estimated for the intra- and inter-reader measurements of the "ATD" angles. Reader A was able to quantify ATD angles on 149 out of 200 prints (74.5%), and Reader B on 179 out of 200 prints (89.5%). Both readers agreed on whether an angle existed on a print 89.8% of the time for the right hand and 78.0% for the left. Intra-reader correlations were 0.97 or greater for both readers. Inter-reader correlations for "ATD" angles measured by both readers ranged from 0.92 to 0.96. These results suggest that the "ATD" angle can be measured reliably, and further imply that measurement using a software program may provide an advantage over other methods. PMID- 26898085 TI - Visual vs. Spectrophotometric Methods for Shade Selection. AB - The differences in tooth colour are important factors in the esthetic dentistry. The aim of this study was to determine the tooth colour using visual methods under natural light and "Easy Shade" device. Five hundred patients of Dental Clinic Graz Austria were selected for this study. The results of this study showed that the shade matching using "Easy Shade" device were not better than shade matching with visual methods under natural light. No difference was found between visual and digital methods in the selection of a tooth shade. PMID- 26898086 TI - The Gap between the Knowledge and Current Practices--A Case of Tobacco Control Programs in Croatia. AB - Despite the availability of numerous evidence-based smoking prevention and cessation programs, many countries are still not implementing these research proven programs. The primary aim of this paper is to summarize the extent to which evidence-based smoking control programs have been implemented in Croatia over the last two decades. Data from the systematic reviews of the Cochrane Tobacco Addiction Group, which are readily available worldwide, were used as criteria to evaluate whether effective, evidence-based programs have been implemented in Croatia. According to our findings, the most effective behavioral and pharmacological smoking cessation interventions have thus far been underutilized in Croatia. In addition, some interventions that have been continuously implemented in Croatia--such as using self-help materials, school based programs and the celebration of World No Tobacco Day--have only small, short-term beneficial effects according to the Cochrane reviews. However, Croatia is a party to the World health Organization Framework Convention on Tobacco Control and therefore has effective national legislation on tobacco control. Croatia should develop and implement programs that integrate the existing high quality empirical evidence on the effectiveness of various behavioral, pharmacological, and social interventions for smoking prevention and cessation. This programming should become a part of a continuous national strategy, and should be implemented throughout all of Croatia. PMID- 26898088 TI - [31P Magnetic Resonance Spectroscopy in Patients With Various Genesis of Left Ventricular Hypertrophy]. AB - PURPOSE: to assess status of myocardial energy metabolism in patients with different etiology of left ventricular hypertrophy by phosphorus magnetic resonance spectroscopy (MRS) compared with healthy individuals. METHODS: The study included 94 people: 30 healthy volunteers (group 1), 35 patients with arterial hypertension and left ventricular hypertrophy (group II), 29 patients with hypertrophic cardiomyopathy (group III). All persons underwent cardiac magnetic resonance imaging (MRI) and MRS on high field MR scanner. Energy metabolism index (ratio of phosphocreatine and adenosine triphosphate concentrations [Pcr/ATP]) was used for evaluation of myocardial energy metabolism. RESULTS: Values of Pcr/ATP were 2.11 +/- 0.29, 1.65 +/- 0.12, and 1.32 +/- 0.16 in groups I, II, and III, respectively (p < 0.05). CONCLUSION: 31P MRS is an effective tool of detection of disordered energy metabolism in hypertrophic myocardium. Combined use of MRI and MRS can become an effective method of comprehensive study of the heart. PMID- 26898087 TI - The Epidemiological Characteristics of Hepatitis B in Croatia: The Results of the Prevention. AB - This study shows epidemiological characteristics and preventive measures implemented for the prevention and control of hepatitis B infections in Croatia. We analyzed the data from obligatory infectious disease reports and notifications of death due to infectious diseases, data on the hepatitis B infections in Croatia, and data collected by survey of the population. The average prevalence of the disease is 3.67 per 100,000 annually. All age groups are affected, but still a higher rate of the disease is found in the age groups from 15-19 and 20 29 years of age. Hepatitis B disease is 1.4 times more likely in men than in women. For the past 18 years, the average rate of mortality was 0.2%. The incidence of HbsAg-positive donors of blood is within the range of 0.65% in 1992 to 0.012% in 2011. The largest part of preventive measures implemented in Croatia against hepatitis B is predicted and required by legislation. The registrations of acute and chronic carriers of the virus are obligatory. High-risk groups have started being vaccinated since 1992. The obligatory vaccination of infants was introduced in the mandatory vaccination program in 2007. Routine testing of blood exclusively from voluntary donors for HbsAg presence is obligatory. The non governmental organization "Help" created for intravenous drug users, along with the "Harm reduction" program implemented hepatitis B, C, and HIV/AIDS prevention program in 1995. In order to gain a better understanding of epidemiological characteristics of hepatitis B in Croatia, the specifics of its dynamics in small communities are required since the research of Croatian public health officials and researchers have shown that hepatitis B is spread in different ways. PMID- 26898089 TI - [Study TRIUMVIRATE: Reducing the Risk of Cardiovascular Events in Hypertensive Patients Using Triple Combination Antihypertensive and Lipid-Lowering Drugs]. PMID- 26898090 TI - [Efficiency of Pulmonary Ventilation in Remote Period After Surgery in Patients With Chronic Pulmonary Thromboembolism]. AB - AIM: to assess efficiency of pulmonary ventilation in remote period after surgical treatment of chronic pulmonary thromboembolism (CPTE). MATERIAL AND METHODS: We examined 29 patients with CPTE with median age 49 (38-60) years. Pulmonary ventilation was studied by body plethysmography and its efficiency was evaluated by oxygen utilization coefficient (OUC). RESULTS: Comparison of OUCs before and in the remote period after surgery showed that after surgical treatment efficiency of pulmonary ventilation increased by 26% at the account of reduced hyperventilation but remained below normal. Patients' age and duration of the disease had a direct impact on the baseline bronchial conductivity as well as on recovery of the respiratory system reserve in the remote period after surgery. PMID- 26898091 TI - [Experience of Endovascular Implantation of the WATCHMAN Device in Patients With Atrial Fibrillation]. AB - Atrial fibrillation is one of most frequent heart rhythm disorders in clinical practice. In this article, we present data of review of relevant literature including consideration of prevention of thromboembolic complications. We also present our own experience of endovascular implantation of the WATCHMAN device in left atrial appendage of patients with atrial fibrillation. PMID- 26898092 TI - [Paradox of Obesity and Cardiovascular Mortality]. AB - Obesity is known as an independent risk factor of a number of chronic noninfectious disorders, however some investigations testify to the presence of "obesity paradox". The aim of the present review was to analyze results of investigations purposed to assess the effect of an elevated body mass index (BMI) and obesity on hospital mortality, risk of complications, and long term prognosis (mortality rate). Effect of BMI dynamics during lifespan on (cardiovascular ?) mortality was also analyzed. The results failed to demonstrate any convincing evidences that BMI 25-35 kg/m2 alone without taking into consideration metabolic changes, waist measurements, correlation between fat and muscular tissue was a risk factor of higher mortality in the long-term prospect and that its decrease improved survival. At the same time, it should be noted that these results depended on the method of sample formation and approaches to the statistical analysis. PMID- 26898093 TI - [Twenty Years' Experience of the Surgical Treatment of Giant Ascending Aortic Aneurysms]. AB - Giant ascending aortic aneurysm is one of the worst lesions of the cardiovascular system. Timely surgical treatment provides the only chance to prolong the lives of such patients. Life expectancy without surgery in these patients is minimal; they die from a ruptured aneurysm or decompensation of organs and systems. In this paper, based on two decades' experience of treating patients with giant aneurysms of ascending aorta and aortic arch in B.V. Petrovsky National Research Center of Surgery we have assessed evaluated immediate results of surgery and proposed measures for prevention of possible complications. Out of 53 patients with giant. ascending aortic aneurysms spontaneous rupture after sternotomy or opening of the pericardium occurred in 5 cases. Overall hospital mortality was 1.9%. Our results indicate that with the right tactics surgical repair of giant ascending aortic aneurysms can be performed with a low mortality. Preliminary cardiopulmonary bypass with peripheral cannulation and cooling prior to sternotomy for the possibility of circulatory arrest is a prerequisite of the prevention of fatal massive hemorrhage. PMID- 26898094 TI - [Analysis of the Effectiveness of Renoprotection of Low-Protein Diet and Ketoanalogues of Amino Acids In Patients With Chronic Kidney Disease]. AB - AIM: Analysis of the effectiveness of renoprotection in patients with chronic kidney disease (CKD), who is observed by general practitioners for up to 72.1 months, keeping traditional LPD or LPD with prescription of ketoanalogues of amino acids (KA/AK). METHODS: 63 patients with CKD stages 3-4, mainly with glomerulonephritis (GN), were divided into 3 groups: 1 gr--31 patients (53.3 +/- 3.1 years old; M/F--18/13), LPD with prescription of ketoanalogues of amino acids; 2 gr--22 patients (54.9 3.2 years old; M/F--13/9) traditional LPD without ketoanalogues; 3 gr--10 patients (51.7 +/- 4.2 years old; M/F--6/4) with natural course of CKD. Group 4 (control)--30 healthy subjects (52.3 +/- 2.2 years old; M/F--16/14). The following parameters were studied: dynamics of the glomerular filtration rate (GFR), systolic blood pressure (SBP), diastolic blood pressure (DBP), hemoglobin levels (Hb), daily proteinuria, and basic parameters of protein, lipid and phosphate- calcium metabolism. RESULTS: The rate of decline in GFR was significantly lower in patients of the first group (-0.78 mL/min/year) than those of the second group (-4.9 ml/min/year). 9.7% of patients of the first group needed the start of renal replacement therapy at the end of the observation, 18.1%--of the second group and 40%--of the third. All patients who received renoprotective therapy, including low-protein diet with KA/AA reached target levels of blood pressure < 140/90 mm Hg. Patients of this group was able to achieve a significant reduction in proteinuria, improvement of lipid metabolism, prevent of reduction of Hb and the development of metabolic disorders of protein and calcium-phosphate metabolism. The second group of patients, following nephroprotection recommendations and LPD without KA/AA, had fewer reductions in BP without reaching the target level, DBP did not change; reduction of proteinuria was less significant than in group 1. There was no negative dynamics of protein and calcium-phosphate metabolism, though significantly increased levels of total cholesterol and LHD were observed. The third group of patients, who did not follow the renoprotection recommendations demonstrated negative dynamics of the studied parameters. CONCLUSION: Renoprotection based on the use KA/AA in patients with CKD stages 3-4 proved to be more effective than without it in slowing the rate of decline in GFR, hypertension correction, proteinuria reduction, maintaining the level of Hb, prevention of disorders of protein and calcium-phosphate metabolism, as well as correction of the lipid metabolism. PMID- 26898095 TI - [HAS-BLED and HEMORR2HAGES Scales in Assessment of Bleeding Risk in Patients on Long-Term Warfarin Therapy]. AB - Aim of the study was to elucidate value of HAS-BLED and HEMORR2HAGES scales for prediction bleedings in patients receiving long-term warfarin (W) therapy. MATERIAL AND METHODS: The study involved 119 patients (72 men) aged 60.9 +/- 9.6 years with atrial fibrillation or venous thromboembolic complications. Follow up period was 5.6 +/- 3.4 years. All bleedings were categorized as 1) single bleeding with INR > 4.0 during the 1st month of W therapy; 2) any single bleeding after 1st month of W therapy; 3) recurrent bleedings. CYP2C9 and VKORC1 (G3673A) genotypic variants were determined by PCR. Patients were divided into low (< 3 points of HAS-BLED scale, n = 58; < 4 points of HEMORR2HAGES scale, n = 109) and high (3 points of HAS-BLED scale, n = 61, >= 4 points of HEMORR2HAGES scale, n = 10) bleeding risk groups. RESULTS: There was no relationship between total HAS BLED, HEMORR2HAGES scores and numbers of all as well as category 1 and 2 bleedings. The difference in bleeding frequency between high and low risk groups was significant only for recurrent bleedings. There were 22 (36.1%) and 5 (8.6%) recurrent bleedings among 61 and 58 patients with high and low-risk HAS-BLED score, respectively (p = 0.0048). Recurrent bleedings also occurred more frequently among patients with high risk (7/10, 70%) compared with low risk (20/109, 18.35%) HEMORR2HAGES score (p = 0.018). Subgroups of high and low bleeding risk according to HAS-BLED and HEMORR2HAGES scores differed only by proportion of patients with recurrent bleedings. High W sensitivity represented by 2*/2*, 2*/3*, 3*/3* CYP2C9 and/or AA VKORC1 homozygosis was detected in 25 of 119 patients. Six of 8 patients (75%) with category 1 bleedings were carriers of any polymorpism. CONCLUSION: HAS-BLED and HEMORR2HAGES scales performed best in predicting recurrent bleedings in patients on long term W therapy. Single bleedings with INR > 4.0 during 1st month of W therapy were associated with reduced W metabolism (AA VKORC1 or/and CYP2C9 allelic variants 2*/2*, 2*/3*, 3*/3*). PMID- 26898096 TI - [Interrelationship of Matrix Metalloproteinase-9 and Its Tissue Inhibitor-1 and Blood Lipid Profile of Patients With Carotid Atherosclerosis]. PMID- 26898097 TI - [Therapeutic Angiogenesis Using Growth Factors: Current State and Prospects for Development]. AB - Therapeutic angiogenesis has been in use for treatment of ischemic diseases for about 15 years. During this period of successes and failures this field has accumulated a significant amount of published and ongoing surveys giving insights and raising new questions and problems. One of the most utilized methods for therapeutic angiogenesis suggests introduction of angiogenic growth factors (VEGF, bFGF, angiopoietin-1 etc.) into ischemic tissues. Still, there is a whole range of problems regarding the efficacy of therapeutic angiogenesis. These can be potentially circumvented by use of new delivery methods, development of combined approaches and use of more relevant pre-clinical animal models. Present review gives a brief analysis of crucial achievements and issues that has been recently raised in experimental and clinical studies focusing on therapeutic angiogenesis. Final part brings some possible directions for development that can give an opportunity to circumvent current obstacles and provide further development. PMID- 26898098 TI - [Methods of Prevention of Sudden Death in Chronic Heart Failure]. AB - Chronic heart failure (CHF) is a natural finale of all cardiovascular diseases. Its prevalence in Russian Federation (as assessed using traditional Framingham criteria) is 4.5% what corresponds to 5 million patients. Prognosis of decompensation of cardiac action remains unfavorable even at the background of optimal drug therapy and use of nondrug methods of treatment. Main causes of death of patients with CHF are cardiac decompensation and sudden cardiac death (SCD). In this review, we present analysis of Russian and foreign studies which have investigated immediate causes of SCD as well as methods of its primary and secondary prevention. PMID- 26898099 TI - [Isolated Systolic Hypertension in Different Ages]. AB - Hypertension is the leading risk-factor for cardiovascular disease and death from them. Traditionally, the problem of isolated systolic hypertension is associated with old age in mind the natural dynamics of systolic and diastolic blood pressure throughout life. Isolated systolic hypertension is the most common type of hypertension in elderly men as well as young adults. The pathophysiology of this condition in different age periods have fundamental differences. The adverse prognostic significance of isolated systolic hypertension in the elderly, and the need for its non-drug and drug treatment are well documented. Accumulating epidemiological evidence on the adverse prognostic significance of isolated systolic hypertension. People young and middle-aged isolated systolic hypertension heterogeneous and may be a consequence of excessive pulse pressure amplification from the aorta to the peripheral arteries and the manifestation of an accelerated aging. Evaluation of central blood pressure and arterial stiffness in young may help identify premature vascular aging. PMID- 26898100 TI - [Methods of Assessment of the Right Ventricular Function]. AB - The review contains contemporary data of assessment on right ventricular (RV) function by various instrumental methods of investigation. Among all these methods multispiral computed tomography (MSCT) appears to be most perspective. Accuracy and reproducibility of measurements of RV function by MSCT and comparable with those of magnetic resonance tomography. The uniqueness of MSCT is its ability to produce complex simultaneous evaluation not only of RV-functional parameters but also of other anatomical structures located in the scanning field. PMID- 26898101 TI - [Endocardial Electrophysiological Study in an Asymptomatic Competitive Athlete With Ventricular Preexitation due to Conduction via Fasciculoventricular Accessory Pathway]. AB - We present a clinical case of a rare form of the WPW phenomenon due to anterograde conduction over fasciculoventricular accessory pathway in 20-year-old competitive athlete. The patient had no history of palpitations or syncope. ECG revealed shortening of PQ interval (112 ms) and wide QRS complex due to conduction via accessory pathway. To address the question of participation in competitive activity and the need for ablation the patient underwent endocardial electrophysiological study in the course of which we verified conduction via fasciculoventricular accessory pathway. The result of the study was used in determination of strategy of further management. PMID- 26898102 TI - Inverse trends of Campylobacter and Salmonella in Swiss surveillance data, 1988 2013. AB - Clinical isolates of Campylobacter spp. and Salmonella spp. are notifiable in Switzerland. In 1995, Campylobacter replaced Salmonella as the most frequently reported food-borne pathogen. We analysed notification data (1988-2013) for these two bacterial, gastrointestinal pathogens of public health importance in Switzerland. Notification rates were calculated using data for the average resident population. Between 1988 and 2013, notified campylobacteriosis cases doubled from 3,127 to 7,499, while Salmonella case notifications decreased, from 4,291 to 1,267. Case notifications for both pathogens peaked during summer months. Campylobacter infections showed a distinct winter peak, particularly in the 2011/12, 2012/13 and 2013/14 winter seasons. Campylobacter case notifications showed more frequent infection in males than females in all but 20-24 year-olds. Among reported cases, patients' average age increased for campylobacteriosis but not for salmonellosis. The inverse trends observed in case notifications for the two pathogens indicate an increase in campylobacteriosis cases. It appears unlikely that changes in patients' health-seeking or physicians' testing behaviour would affect Campylobacter and Salmonella case notifications differently. The implementation of legal microbiological criteria for foodstuff was likely an effective means of controlling human salmonellosis. Such criteria should be decreed for Campylobacter, creating incentives for producers to lower Campylobacter prevalence in poultry. PMID- 26898103 TI - In Vitro Fermentation of Porcine Milk Oligosaccharides and Galacto oligosaccharides Using Piglet Fecal Inoculum. AB - In this study, the in vitro fermentation by piglet fecal inoculum of galacto oligosaccharides (GOS) and porcine milk oligosaccharides (PMOs) was investigated to identify possible preferences for individual oligosaccharide structures by piglet microbiota. First, acidic PMOs and GOS with degrees of polymerization 4-7 were depleted within 12 h of fermentation, whereas fucosylated and phosphorylated PMOs were partially resistant to fermentation. GOS structures containing beta1-3 and beta1-2 linkages were preferably fermented over GOS containing beta1-4 and beta1-6 linkages. Upon in vitro fermentation, acetate and butyrate were produced as the main organic acids. GOS fermentation by piglet inoculum showed a unique fermentation pattern with respect to preference of GOS size and organic acids production. PMID- 26898104 TI - Design and synthesis of novel flexible ester-containing analogs of tamoxifen and their evaluation as anticancer agents. AB - BACKGROUND: Tamoxifen (TAM) is metabolized to the more active 4-hydroxytamoxifen by CYP2D6 enzyme. Due to the genetic polymorphisms in CYP2D6, clinical outcomes of TAM treatment vary. Novel flexible TAM analogs with altered activation pathway were synthesized and were tested for their antiproliferative action on MCF-7 cell lines and their binding affinity for ERalpha and ERbeta. RESULTS: All compounds showed better antiproliferative activity than TAM. Compound 3 showed 80-times more ERalpha binding than TAM, 900-times more selectivity toward ERalpha. Compound 3 was tested on the entire National Cancer Institute cancerous cell lines; results indicated a broad spectrum anticancer activity. CONCLUSION: The novel analogs were more potent than TAM with higher selectivity toward ERalpha and with potential metabolic stability toward CYP2D6. PMID- 26898105 TI - An effective calibration technique for radiochromic films using a single-shot dose distribution in Gamma Knife((r)). AB - PURPOSE: A method of calibrating radiochromic films for Gamma Knife((r)) (GK) dosimetry was developed. The applicability and accuracy of the new method were examined. METHODS: The dose distribution for a sixteen millimeter single-shot from a GK was built using a reference film that was calibrated using the conventional multi-film calibration (MFC) method. Another film, the test film, from a different set of films was irradiated under the same conditions as the reference film. The calibration curve for the second set of films was obtained by assigning the dose distribution of the reference film to the optical density of the test film, point by point. To assess the accuracy of this single-film calibration (SFC) method, differences between gamma index pass rates (GIPRs) were calculated. RESULTS: The SFC curves were successfully obtained with estimated errors of 1.46%. GIPRs obtained with the SFC method for films irradiated using a single-shot showed differences less than one percentage point when dose difference criterion (DeltaD) was 2% and the distance to agreement criterion (Deltad) was 1 mm. The GIPRs of the SFC method when the films were irradiated following a virtual target treatment plan were consistent with the GIPRs of the MFC method, with differences of less than 0.2 percentage points for DeltaD = 1% and Deltad = 1 mm. CONCLUSION: The accuracy of the SFC method is comparable to that of conventional multi-film calibration method for GK film dosimetry. PMID- 26898106 TI - Comparison between In-house developed and Diamond commercial software for patient specific independent monitor unit calculation and verification with heterogeneity corrections. AB - The study was aimed to compare two different monitor unit (MU) or dose verification software in volumetric modulated arc therapy (VMAT) using modified Clarkson's integration technique for 6 MV photons beams. In-house Excel Spreadsheet based monitor unit verification calculation (MUVC) program and PTW's DIAMOND secondary check software (SCS), version-6 were used as a secondary check to verify the monitor unit (MU) or dose calculated by treatment planning system (TPS). In this study 180 patients were grouped into 61 head and neck, 39 thorax and 80 pelvic sites. Verification plans are created using PTW OCTAVIUS-4D phantom and also measured using 729 detector chamber and array with isocentre as the suitable point of measurement for each field. In the analysis of 154 clinically approved VMAT plans with isocentre at a region above -350 HU, using heterogeneity corrections, In-house Spreadsheet based MUVC program and Diamond SCS showed good agreement TPS. The overall percentage average deviations for all sites were ( 0.93% + 1.59%) and (1.37% + 2.72%) for In-house Excel Spreadsheet based MUVC program and Diamond SCS respectively. For 26 clinically approved VMAT plans with isocentre at a region below -350 HU showed higher variations for both In-house Spreadsheet based MUVC program and Diamond SCS. It can be concluded that for patient specific quality assurance (QA), the In-house Excel Spreadsheet based MUVC program and Diamond SCS can be used as a simple and fast accompanying to measurement based verification for plans with isocentre at a region above -350 HU. PMID- 26898107 TI - Hydrodynamic body shape analysis and their impact on swimming performance. AB - This study presents the hydrodynamic characteristics of different adult male swimmer's body shape using computational fluid dynamics method. This simulation strategy is carried out by CFD fluent code with solving the 3D incompressible Navier-Stokes equations using the RNG k-epsilon turbulence closure. The water free surface is captured by the volume of fluid (VOF) method. A set of full body models, which is based on the anthropometrical characteristics of the most common male swimmers, is created by Computer Aided Industrial Design (CAID) software, Rhinoceros. The analysis of CFD results revealed that swimmer's body shape has a noticeable effect on the hydrodynamics performances. This explains why male swimmer with an inverted triangle body shape has good hydrodynamic characteristics for competitive swimming. PMID- 26898108 TI - Identification of a novel HLA-C allele, HLA-C*03:313, in a Japanese individual. AB - HLA-C*03:313 differs from HLA-C*03:04:01:01 by one non-synonymous amino acid exchange E161G. PMID- 26898109 TI - Left main coronary artery atresia in an infant with Shone's complex. AB - A 6-month-old infant with Shone's complex was found to have left main coronary artery atresia during evaluation for recurrent subaortic stenosis with depressed left ventricular function. The ventricular function improved after surgical subaortic resection without coronary re-vascularisation. This case demonstrates first the rare finding of left main coronary artery atresia and second that coronary re-vascularisation is not necessarily required in all cases of left main coronary artery atresia. PMID- 26898112 TI - Mucosal immunology: Weaning off food allergy. PMID- 26898113 TI - Allergy: You're born with it. PMID- 26898114 TI - Cultures of engagement: The organizational foundations of advancing health in immigrant and low-income communities of color. AB - A rich civic infrastructure of community-based organizations (CBOs) can help generate, diffuse and maintain a culture of engagement and health that benefits marginalized populations most at risk for illness, disability, and poor health. Attention to CBOs advances "meso-level" frameworks for understanding health cultures and outcomes by going beyond attention to social networks and social identities. We focus on three mechanisms: CBOs can (1) empower individuals by developing civic capacity and personal efficacy; (2) foster solidarity by building networks, social identities and a shared commitment to collective well being; and (3) mobilize people to have a voice in health-related policies and programming, thereby affecting community well-being. We draw on theory and research in sociology, political science and psychology, and we illustrate the utility of a CBO approach by examining survey and semi-structured interview data from participants in youth civic groups in 13 low-income, predominantly immigrant communities in California. Interview data illustrate the ways in which CBOs enhance members' civic capacities, provide a sense of empowerment and efficacy to engage in healthy behaviors, develop solidarity among diverse participants, and elaborate networks among those committed to community well-being. We also discuss CBO-led campaigns in which youth mobilized for change in policies and practices of local institutions to illustrate possible community-wide health consequences of CBO engagement. CBOs can thus generate individual-level well-being effects, and reduce structural barriers to good health through changes in the broader environment. PMID- 26898110 TI - Mucosal immunity to pathogenic intestinal bacteria. AB - The intestinal mucosa is a particularly dynamic environment in which the host constantly interacts with trillions of commensal microorganisms, known as the microbiota, and periodically interacts with pathogens of diverse nature. In this Review, we discuss how mucosal immunity is controlled in response to enteric bacterial pathogens, with a focus on the species that cause morbidity and mortality in humans. We explain how the microbiota can shape the immune response to pathogenic bacteria, and we detail innate and adaptive immune mechanisms that drive protective immunity against these pathogens. The vast diversity of the microbiota, pathogens and immune responses encountered in the intestines precludes discussion of all of the relevant players in this Review. Instead, we aim to provide a representative overview of how the intestinal immune system responds to pathogenic bacteria. PMID- 26898111 TI - Mutations, kataegis and translocations in B cells: understanding AID promiscuous activity. AB - As B cells engage in the immune response, they express activation-induced cytidine deaminase (AID) to initiate the hypermutation and recombination of immunoglobulin genes, which are crucial processes for the efficient recognition and disposal of pathogens. However, AID must be tightly controlled in B cells to minimize off-target mutations, which can drive chromosomal translocations and the development of B cell malignancies, such as lymphomas. Recent genomic and biochemical analyses have begun to unravel the mechanisms of how AID-mediated deamination is targeted outside immunoglobulin genes. Here, we discuss the transcriptional and topological features that are emerging as key drivers of AID promiscuous activity. PMID- 26898116 TI - Musical and poetic creativity and epilepsy. AB - Associations between epilepsy and musical or poetic composition have received little attention. We reviewed the literature on links between poetic and musical skills and epilepsy, limiting this to the Western canon. While several composers were said to have had epilepsy, John Hughes concluded that none of the major classical composers thought to have had epilepsy actually had it. The only composer with epilepsy that we could find was the contemporary composer, Hikari Oe, who has autism and developed epilepsy at age 15years. In his childhood years, his mother found that he had an ability to identify bird sound and keys of songs and began teaching him piano. Hikari is able to compose in his head when his seizures are not severe, but when his seizures worsen, his creativity is lost. Music critics have commented on the simplicity of his musical composition and its monotonous sound. Our failure to find evidence of musical composers with epilepsy finds parallels with poetry where there are virtually no established poets with epilepsy. Those with seizures include Lord George Byron in the setting of terminal illness, Algernon Swinburne who had alcohol-related seizures, Charles Lloyd who had seizures and psychosis, Edward Lear who had childhood onset seizures, and Vachel Lindsay. The possibility that Emily Dickinson had epilepsy is also discussed. It has not been possible to identify great talents with epilepsy who excel in poetic or musical composition. There are few published poets with epilepsy and no great composers. Why is this? Similarities between music and poetry include meter, tone, stress, rhythm, and form, and much poetry is sung with music. It is likely that great musical and poetic compositions demand a greater degree of concentration and memory than is possible in epilepsy, resulting in problems retaining a musical and mathematical structure over time. The lack of association between recognizable neuropsychiatric disorders and these skills is a gateway to understanding facets of the relationship between the brain and creativity. This article is part of a Special Issue entitled "Epilepsy, Art, and Creativity". PMID- 26898115 TI - Enhancing cytochrome P450-mediated conversions in P. pastoris through RAD52 over expression and optimizing the cultivation conditions. AB - Cytochrome P450 enzymes (CYPs) play an essential role in the biosynthesis of various natural compounds by catalyzing regio- and stereospecific hydroxylation reactions. Thus, CYP activities are of great interest in the production of fine chemicals, pharmaceutical compounds or flavors and fragrances. Industrial applicability of CYPs has driven extensive research efforts aimed at improving the performance of these enzymes to generate robust biocatalysts. Recently, our group has identified CYP-mediated hydroxylation of (+)-valencene as a major bottleneck in the biosynthesis of trans-nootkatol and (+)-nootkatone in Pichia pastoris. In the current study, we aimed at enhancing CYP-mediated (+)-valencene hydroxylation by over-expressing target genes identified through transcriptome analysis in P. pastoris. Strikingly, over-expression of the DNA repair and recombination gene RAD52 had a distinctly positive effect on trans-nootkatol formation. Combining RAD52 over-expression with optimization of whole-cell biotransformation conditions, i.e. optimized media composition and cultivation at higher pH value, enhanced trans-nootkatol production 5-fold compared to the initial strain and condition. These engineering approaches appear to be generally applicable for enhanced hydroxylation of hydrophobic compounds in P. pastoris as confirmed here for two additional membrane-attached CYPs, namely the limonene-3 hydroxylase from Mentha piperita and the human CYP2D6. PMID- 26898117 TI - Magnetostructural phase transition assisted by temperature in Ag-alphaMnO2: a density functional theory study. AB - A crystalline material formed by parallel chains of silver atoms inside one dimensional tunnels of hollandite manganese dioxide, Ag-alphaMnO2, is investigated through first-principles total energy calculations. Two different magnetic phases have been identified; one structure containing linear Ag chains with an antiferromagnetic ordering in the direction perpendicular to the MnO2 tunnels for T = 0 K (I4/m) and another configuration with zigzag Ag chains in a non-magnetic regime for higher temperatures (P21/c). According to phonon dispersions, both structures are stable. On the other hand, the structure with linear Ag chains in the non-magnetic state is unstable. A critical temperature of Tc? 125 K for the magnetostructural phase transition between the two stable structures I4/m and P21/c is predicted. PMID- 26898118 TI - Trends in Invasive Prenatal Diagnosis: Effect of Sequential Screening and Noninvasive Prenatal Testing. AB - OBJECTIVE: To examine trends in the incidence and method of invasive prenatal diagnosis due to the impact of sequential screening and noninvasive prenatal testing. METHODS: This is a retrospective review of all pregnancies that have undergone invasive prenatal diagnostic testing between June 2002 and June 2014, divided in 3 periods: period 1 from June 2002 to October 2006, period 2 from November 2006 to December 2011, and period 3 from January 2012 to June 2014. The main outcome measures were trends in the incidence and method of each procedure. RESULTS: There were 88,135 deliveries and 6,080 invasive procedures during the study period. In period 1, 2,755 (8.8%) procedures were carried out, in period 2 2,820 (7.3%), and in period 3 505 (2.5%; p < 0.01). In period 1, there were 1,990 (6.3%) cases of amniocentesis, 1,646 (4.3%) in period 2, and 254 (1.2%) in period 3 (p < 0.01). In addition, in 765 (2.5%) cases, chorionic villus sampling (CVS) was performed in period 1, compared to 1,174 (3.0%) cases in period 2 and 251 (1.3%) cases in period 3 (p < 0.01). Advanced maternal age as the sole indication for invasive procedures decreased significantly over time, while the indication of abnormal serum screening and abnormal ultrasound findings increased (p < 0.01). CONCLUSION: There was a significant decline in the incidence of invasive prenatal testing over the 12 years of the study. The decrease in amniocentesis was more marked than that in CVS. PMID- 26898119 TI - Serum cytokine profile in patients with breast cancer. AB - Breast cancer is the leading cause of cancer-related death among women, with a more 20% 5-year survival rate after metastases. It is therefore critical to improve early diagnosis in order to improve disease prognosis. This study investigates cytokine profiles of breast cancer serum with the aim of identifying biomarkers for early diagnosis. A solid-phase antibody array was used for screening 274 biomarkers in serum from breast cancer patients. ELISA assay was carried out to identify biomarkers with differential expression. The serum levels of IL-8, MIP-1 alpha, MIP-1 beta, MMP-8, Resistin, FLRG, and BCAM were significantly higher in breast cancer patients, but LAP and TSH-beta levels were lower. ELISA assay results confirmed those of the antibody array. Our results suggest that these cytokines, screened by antibody array, might serve as novel inflammatory markers in breast cancer patients. Whether these biomarkers are specific for breast cancer and can help to improve diagnoses and prognoses of breast cancer needs further investigation. PMID- 26898121 TI - Soil organic carbon dynamics under long-term fertilization in a black soil of China: Evidence from stable C isotopes. AB - Effects of different fertilizers on organic carbon (C) storage and turnover of soil fractions remains unclear. We combined soil fractionation with isotope analyses to examine soil organic carbon (SOC) dynamics after 25 years of fertilization. Five types of soil samples including the initial level (CK) and four fertilization treatments (inorganic nitrogen fertilizer, N; balanced inorganic fertilizer, NPK; inorganic fertilizer plus farmyard manure, MNPK; inorganic fertilizer plus corn straw residue, SNPK) were separated into four aggregate sizes (>2000 MUm, 2000-250 MUm, 250-53 MUm, and <53 MUm), and three density fractions: free light fraction (LF), intra-aggregate particulate organic matter (iPOM), and mineral-associated organic matter (mSOM). Physical fractionation showed the iPOM fraction of aggregates dominated C storage, averaging 76.87% of SOC storage. Overall, application of N and NPK fertilizers cannot significantly increase the SOC storage but enhanced C in mSOM of aggregates, whereas MNPK fertilizer resulted in the greatest amount of SOC storage (about 5221.5 g C m(2)) because of the enhanced SOC in LF, iPOM and mSOM of each aggregate. The SNPK fertilizer increased SOC storage in >250 MUm aggregates but reduced SOC storage in <250 MUm aggregates due to SOC changes in LF and iPOM. PMID- 26898120 TI - Imbalanced production of IL-18 and its antagonist in human diseases, and its implications for HIV-1 infection. AB - IL-18 is a pleiotropic and multifunctional cytokine that belongs to the IL-1 family. It is produced as a biologically inactive precursor, which is cleaved into its active mature form mainly by caspase-1. The caspase becomes active from its inactive precursor (procaspase-1) upon assembly of an inflammasome. Because of IL-18's potential pro-inflammatory and tissue destructive effects, its biological activities are tightly controlled in the body by its naturally occurring antagonist called IL-18BP. The antagonist is produced in the body both constitutively and in response to an increased production of IL-18 as a negative feedback mechanism. Under physiological conditions, most of IL-18 in the circulation is bound with IL-18BP and is inactive. However, an imbalance in the production of IL-18 and its antagonist (an increase in the production of IL-18 with a decrease, no increase or an insufficient increase in the production of IL 18BP) has been described in many chronic inflammatory diseases in humans. The imbalance results in an increase in the concentrations of free IL-18 (unbound with its antagonist) resulting in increased biological activities of the cytokine that contribute towards pathogenesis of the disease. In this article, we provide an overview of the current biology of IL-18 and its antagonist, discuss how the imbalance occurs in HIV infections and how it contributes towards development of AIDS and other non-AIDS-associated clinical conditions occurring in HIV-infected individuals undergoing combination anti-retroviral therapy (cART). Finally, we discuss challenges facing immunotherapeutic strategies aimed at restoring balance between IL-18 and its antagonist in these patients. PMID- 26898122 TI - Methylglyoxal activates NF-kappaB nuclear translocation and induces COX-2 expression via a p38-dependent pathway in synovial cells. AB - AIMS: There is growing evidence of an increased prevalence of osteoarthritis (OA) among people with diabetes. Synovial inflammation and increased expression of cyclooxygenase-2 (COX-2) are two key features of patients with OA. Methylglyoxal (MGO) is a common intermediate in the formation of advanced glycation end products, and its concentration is also typically higher in diabetes. In this study, we investigated the effects of the treatment of different MGO concentrations to rabbit HIG-82 synovial cells on COX-2 expression. MAIN METHODS: The MGO induced COX-2 mRNA expression was detected by quantitative polymerase chain reaction. The MGO induced COX-2 protein production and its signaling pathways were detected by western blotting. The nuclear factor-kappa B (NF kappaB) nuclear translocation by MGO was examined by immunofluorescence. KEY FINDINGS: In the present study, we find that MGO has no toxic effects on rabbit synovial cells under the experimental conditions. Our analysis demonstrates that MGO induced COX-2 mRNA and protein production. Moreover, MGO induces p38 dependent COX-2 protein expression as well as the phosphorylations of extracellular signal-regulated kinase, c-Jun N-terminal kinase (JNK), and Akt/mammalian target of rapamycin (mTOR)/p70S6K; however, inhibition of JNK and Akt/mTOR/p70S6K phosphorylations further activates COX-2 protein expression. Furthermore, MGO is shown to activate of nuclear factor-kappa B (NF-kappaB) nuclear translocation. SIGNIFICANCE: Our results suggest that MGO can induce COX 2 expression via a p38-dependent pathway and activate NF-kappaB nuclear translocation in synovial cells. These results provide insight into the pathogenesis of the synovial inflammation under the diabetic condition associated with higher MGO levels. PMID- 26898124 TI - Evidence for biased agonists and antagonists at the endothelin receptors. AB - Biased ligands represent a new strategy for the development of more effective and better tolerated drugs. To date there has been a paucity of research exploring the potential of ligands that exhibit either G protein or beta-arrestin pathway selectivity at the endothelin receptors. Re-analysis of data may allow researchers to determine whether there is existing evidence that the endogenous ET peptides or currently available agonists and antagonists exhibit pathway bias in a particular physiological or disease setting and this is explored in the review. An alternative to molecules that bind at the orthosteric site of the ET receptors are cell penetrating peptides that interact with a segment of an intracellular loop of the receptor to modify signalling behaviour. One such peptide IC2B has been shown to have efficacy in a model of pulmonary arterial hypertension. Finally, understanding the molecular pathways that contribute to disease is critical to determining whether biased ligands will provide clinical benefit. The role of ETA signalling in ovarian cancer has been delineated in some detail and this has led to the suggestion that the development of ETA G protein biased agonists or beta-arrestin biased antagonists should be explored. PMID- 26898123 TI - Linagliptin reduces effects of ET-1 and TLR2-mediated cerebrovascular hyperreactivity in diabetes. AB - AIMS: The anti-hyperglycemic agent linagliptin, a dipeptidyl peptidase-4 inhibitor, has been shown to reduce inflammation and improve endothelial cell function. In this study, we hypothesized that DPP-IV inhibition with linagliptin would improve impaired cerebral blood flow in diabetic rats through improved insulin-induced cerebrovascular relaxation and reversal of pathological cerebrovascular remodeling that subsequently leads to improvement of cognitive function. MAIN METHODS: Male type-2 diabetic Goto-Kakizaki (GK) and nondiabetic Wistar rats were treated with linagliptin, and ET-1 plasma levels and dose response curves to ET-1 (0.1-100nM) in basilar arteries were assessed. The impact of TLR2 antagonism on ET-1 mediated basilar contraction and endothelium-dependent relaxation to acetylcholine (ACh, 1nM-1M) in diabetic GK rats was examined with antibody directed against the TLR2 receptor (Santa Cruz, 5MUg/mL). The expression of TLR2 in middle cerebral arteries (MCAs) from treated rats and in brain microvascular endothelial cells (BMVEC) treated with 100nM linagliptin was assessed. KEY FINDINGS: Linagliptin lowered plasma ET-1 levels in diabetes, and reduced ET-1-induced vascular contraction. TLR2 antagonism in diabetic basilar arteries reduced ET-1-mediated cerebrovascular dysfunction and improved endothelium-dependent vasorelaxation. Linagliptin treatment in the BMVEC was able to reduce TLR2 expression in cells from both diabetic and nondiabetic rats. CONCLUSIONS: These results suggest that inhibition of DPPIV using linagliptin improves the ET-1-mediated cerebrovascular dysfunction observed in diabetes through a reduction in ET-1 plasma levels and reduced cerebrovascular hyperreactivity. This effect is potentially a result of linagliptin causing a decrease in endothelial TLR2 expression and a subsequent increase in NO bioavailability. PMID- 26898125 TI - Pulsed electromagnetic fields promote survival and neuronal differentiation of human BM-MSCs. AB - Pulsed electromagnetic fields (PEMF) are known to affect biological properties such as differentiation, regulation of transcription factor and cell proliferation. However, the cell-protective effect of PEMF exposure is largely unknown. The aim of this study is to understand the mechanisms underlying PEMF mediated suppression of apoptosis and promotion of survival, including PEMF induced neuronal differentiation. Treatment of induced human BM-MSCs with PEMF increased the expression of neural markers such as NF-L, NeuroD1 and Tau. Moreover, treatment of induced human BM-MSCs with PEMF greatly decreased cell death in a dose- and time-dependent manner. There is evidence that Akt and Ras are involved in neuronal survival and protection. Activation of Akt and Ras results in the regulation of survival proteins such as Bad and Bcl-xL. Thus, the Akt/Ras signaling pathway may be a desirable target for enhancing cell survival and treatment of neurological disease. Our analyses indicated that PEMF exposure dramatically increased the activity of Akt, Rsk, Creb, Erk, Bcl-xL and Bad via phosphorylation. PEMF-dependent cell protection was reversed by pretreatment with LY294002, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K). Our data suggest that the PI3K/Akt/Bad signaling pathway may be a possible mechanism for the cell-protective effects of PEMF. PMID- 26898127 TI - Carcinoembryonic antigen related cellular adhesion molecule 1 alleviates dextran sulfate sodium-induced ulcerative colitis in mice. AB - AIMS: To investigate the effects of exogenous carcinoembryonic antigen related cellular adhesion molecule 1 (CEACAM1) on ulcerative colitis (UC) in a dextran sulfate sodium (DSS)-induced mouse model. MAIN METHODS: UC mice model was induced by administration of DSS in drinking water for 7days. Treatment of CEACAM1 was performed by a transrectal injection of CEACAM1 gene packed adenovirus in the mice. The severity of UC was evaluated using disease activity index and colon length. Histological changes were observed after hematoxylin and eosin staining. ELISA was used to measure secretion of pro-inflammatory cytokines in the colon tissue. The expression of mRNA and protein were detected using real-time PCR and western blotting. The effect of CEACAM1 on epithelial cell restitution was evaluated using wound-healing test in Caco-2 cells. KEY FINDINGS: CEACAM1 overexpression attenuated the symptoms of UC as evidenced by decreased DAI score, increased colon length and histopathologic score. In addition, exogenous CEACAM1 reduced the levels of inflammatory cytokines and downregulated COX-2 and iNOS expression levels. Moreover, CEACAM1 overexpression decreased colonic permeability by upregulating expression of tight junction proteins. In the in vitro study, exogenous CEACAM1 promoted proliferation and migration of Caco-2 cell. SIGNIFICANCE: Exogenous CEACAM1 effectively rescues the symptoms of UC in DSS mice through preventing inflammatory responses, improving epithelial barrier and promoting epithelial cells restitution. PMID- 26898126 TI - Anxiolytic activity and evaluation of potentially adverse effects of a bradykinin related peptide isolated from a social wasp venom. AB - Anxiety disorders are major health problems in terms of costs stemming from sick leave, disabilities, healthcare and premature mortality. Despite the availability of classic anxiolytics, some anxiety disorders are still resistant to treatment, with higher rates of adverse effects. In this respect, several toxins isolated from arthropod venoms are useful in identifying new compounds to treat neurological disorders, particularly pathological anxiety. Thus, the aims of this study were to identify and characterize an anxiolytic peptide isolated from the venom of the social wasp Polybia paulista. The peptide was identified as Polisteskinin R, with nominal molecular mass [M+H](+)=1301Da and primary structure consisting of Ala-Arg-Arg-Pro-Pro-Gly-Phe-Thr-Pro-Phe-Arg-OH. The anxiolytic effect was tested using the elevated plus maze test. Moreover, adverse effects on the spontaneous behavior and motor coordination of animals were assessed using the open field and rotarod tests. Polisteskinin R induced a dose dependent anxiolytic effect. Animals treated with the peptide and diazepam spent significantly more time into the open arms when compared to the groups treated with the vehicle and pentylenetetrazole. No significant differences in spontaneous behavior or motor coordination were observed between the groups, showing that the peptide was well tolerated. The interaction by agonists in both known BK receptors induces a variability of physiological effects; Polisteskinin R can act on these receptors, inducing modulatory activity and thus, attenuating anxiety behaviors. The results of this study demonstrated that the compound Polisteskinin R exerted potent anxiolytic effects and its analogues are promising candidates for experimental pharmacology. PMID- 26898129 TI - Effects of treadmill exercise intensity on spatial working memory and long-term memory in rats. AB - AIMS: Moderate exercise promotes learning and memory. Most studies mainly focused on memory exercise effects of in the ageing and patients. There is lack of quantitative research about effect of regular exercise intensity on different memory types in normal subjects. Present study investigated the effects of different intensities of treadmill exercise on working memory and long-term memory. MAIN METHODS: Fifty female Wistar rats were trained by T-maze delayed spatial alternation (DSA) task with 3 delays (10s, 60s and 300s). Then they got a 30min treadmill exercise for 30days in 4 intensities (control, 0m/min; lower, 15m/min; middle, 20m/min, and higher, 30m/min). Then animals were tested in DSA, passive avoidance and Morris water maze tasks. KEY FINDINGS: 1. Exercise increased the neuronal density of hippocampal subregions (CA1, CA3 and dentate gyrus) vs. naive/control. 2. In DSA task, all groups have similar baseline, lower intensity improved 10s delay accuracy vs. baseline/control; middle and higher intensities improved 300s delay accuracy vs. baseline/control. 3. In water maze learning, all groups successfully found the platform, but middle intensity improved platform field crossing times vs. control in test phase. SIGNIFICANCE: Present results suggested that treadmill exercise can improve long-term spatial memory and working memory; lower intensity benefits to short-term delayed working memory, and middle or higher intensity benefits to long-term delayed working memory. There was an inverted U dose-effect relationship between exercise intensity and memory performance, but exercise -working memory effect was impacted by delay duration. PMID- 26898130 TI - Mixed Dentition Space Analysis in a Sudanese Population. PMID- 26898128 TI - Prenatal lipopolysaccharide exposure affects sexual dimorphism in different germlines of mice with a depressive phenotype. AB - The objective of the present study was to investigate whether prenatal lipopolysaccharide (LPS) administration modifies the expression of depressive and non-depressive-like behavior in male and female mice across two generations. The sexual dimorphism of these mice was also examined in the open-field test. Male and female mice of the parental (F0) generation were selected for depressive- or non-depressive-like behavioral profiles using the tail suspension test (TST). Animals with similar profiles were matched for further mating. On gestation day (GD) 15, pregnant F0 mice received LPS (100MUg/kg, i.p.) and were allowed to nurture their offspring freely. Adult male and female of the F1 generation were then selected according to behavioral profiles and observed in the open field. Male and female mice of the two behavioral profiles were then mated to obtain the F2 generation. Adults from the F2 generation were also behaviorally phenotyped, and open field behavior was assessed. Male mice that were selected for depressive and non-depressive-like behaviors and treated or not with LPS in the parental generation exhibited similar proportions of behavioral profiles in both filial lines, but LPS exposure increased the number of depressive-like behavior. An effect of gender was observed in the F1 and F2 generations, in which male mice were more sensitive to the intergenerational effects of LPS in the TST. These data indicate that prenatal LPS exposure on GD15 in the F0 generation influenced the transmission of depressive- and non-depressive-like behavior across filial lines, with sexual dimorphism between phenotypes. PMID- 26898131 TI - Preschoolers' Acquisition of Novel Verbs in the Double Object Dative. AB - Children have difficulty comprehending novel verbs in the double object dative (e.g., Fred blicked the dog a stick) as compared to the prepositional dative (e.g., Fred blicked a stick to the dog). We explored this pattern with 3 and 4 year olds (N = 60). In Experiment 1, we replicated the documented difficulty with the double object frame, even though we provided more contextual support. In Experiment 2, we tested a novel hypothesis that children would comprehend novel verbs in, and generalize them to, the double object frame if they were first familiarized to the verbs in the prepositional frame. They did, suggesting that part of their difficulty with the double object frame is due to uncertainty about a new verb's semantic/syntactic properties, information that the easy-to comprehend prepositional frame provides. The benefits of training were short lived, however; children again struggled after a 2-h delay. The results are discussed in the context of mechanisms underlying verb acquisition. PMID- 26898132 TI - Mercury concentration in maternal serum, cord blood, and placenta in patients with amalgam dental fillings: effects on fetal biometric measurements. AB - AIM: We aimed to determine the extent to which mercury is transmitted from the mother to fetus via the umbilical cord in patients with amalgam dental fillings, and its effect on fetal biometric measurements. METHODS: Twenty-eight patients as the study group with amalgam fillings, and 32 of them as the control group were included in this prospective case-control study. The mercury levels were measured in the maternal and cord venous sera, and the placental samples. Two groups were compared in terms of these and the fetal/neonatal biometric measurements. RESULTS: In the study group, the maternal and umbilical cord mercury levels were found to be significantly higher than those from the control group (p = 0.006 and p = 0.010, respectively). These high levels did not affect the fetal biometric measurements. CONCLUSIONS: The presence of high serum mercury levels in pregnant women with amalgam fillings is important, and warrants further long-term studies in order to investigate the fetal neurological effects as well. PMID- 26898133 TI - A comparison between nucleus pulposus-derived stem cell transplantation and nucleus pulposus cell transplantation for the treatment of intervertebral disc degeneration in a rabbit model. AB - INTRODUCTION: In recent years, nucleus pulposus cell (NPC) transplantation has been used to treat intervertebral disc degeneration (IDD); however, the degenerative nature of NPCs influences its effectiveness. Nucleus pulposus derived stem cells (NPSCs), which are self-renewing, have high expansion potential and can adapt to the intervertebral disc (IVD) microenvironment and may have a better regenerative capacity, which is favourable for treating IDD. The aim of this study was to compare the effectiveness of transplantation with NPSCs and NPCs on the regeneration of the IVD in rabbit models. METHODS: NPSCs and NPCs were isolated from human degenerate nucleus pulposus tissue by differential adhesion method, and stem cell surface markers were detected by flow cytometry. Degenerative discs in rabbits were randomly distributed into three groups: NPSCs, NPCs and vehicle control group; the normal discs served as the normal control group. Cells of the P3 generation were prepared for transplantation. About 20 MUl of cell suspension (NPSCs or NPCs) or DMEM was injected into corresponding discs, while the normal discs were left untreated. After 8 weeks, disc height was evaluated using X-ray, water content was evaluated by MRI, and gene and protein expression levels of collagen II and aggrecan in the nucleus were determined by real-time PCR and ELISA. RESULTS: NPCs and NPSCs from the P3 generation were polygonal and spindle-shaped, respectively. Both NPSCs and NPCs strongly expressed surface markers CD73, CD90, and CD105 and weakly expressed CD34 and CD45. The relative rates of expression of CD73, CD90, and CD105 were higher in NPSCs than in NPCs. After 8 weeks, X-ray results showed no significant difference in disc height index among the groups (p > 0.05). MRI revealed that the intensity of the nucleus pulposus signal was increased in NPSCs (p < 0.05). The results from PCR and ELISA demonstrated that NPSCs promoted gene and protein expression of aggrecan instead of collagen II (p < 0.05). CONCLUSION: Compared to NPCs, NPSCs harvested by differential adhesion method displayed a higher positive rate of stem cell surface markers and showed superior regenerative effectiveness for treating IDD in rabbit models. Therefore, NPSCs are potential candidates for cell therapy for the regeneration of the IVD. PMID- 26898134 TI - Ileo-anal pouch surgery in a district general hospital results in good outcomes and high patient satisfaction. AB - INTRODUCTION: Restorative proctocolectomy (RPC) with ileal-pouch anal anastomosis (IPAA) is a technically challenging procedure. This study aims to review the outcomes following surgery carried out in a DGH by two surgeons with experience gained in tertiary centres. MATERIALS AND METHODS: All patients undergoing RPC with IPAA were identified from a prospectively collected database and case notes reviewed. Data were collected on demographics, indication for surgery, operative details, outcomes and adherence to a treatment and follow-up protocol developed with a specialist centre. A validated questionnaire (the Pouch Functional Score) was sent to patients to assess functional outcome. RESULTS: Fourteen patients (nine male) underwent surgery from 2008 to 2012, average age 32 years (range 22 48). Median follow up was 5 years (interquartile range 3.2 years). The indication for surgery was ulcerative colitis. All patients had a 'J' shaped pouch, stapled anastomosis and defunctioning ileostomy. There was no operative mortality. One patient was re-admitted with high ileostomy output; three developed wound infections. All patients have had their stomas closed. There were no postoperative cases of pelvic sepsis or anastomotic leak. The median stool frequency is 6-8/24hrs, 23% of patients reported urgency, 23% had occasional incontinence. The protocol was adhered to in all cases. One patient required defunctioning of the pouch 5 years after surgery. CONCLUSION: With good patient selection, a team approach and a protocol ensuring consistent care, pouch surgery is being performed to a high standard in a DGH setting. Follow-up care is provided locally and patients have easy access to the multidisciplinary team. PMID- 26898135 TI - Minimally invasive percutaneous nephrolithotomy versus endoscopic combined intrarenal surgery with flexible ureteroscope for partial staghorn calculi: A randomised controlled trial. AB - BACKGROUND: To compare the efficacy and safety of simultaneous percutaneous nephrolithotomy combined with flexible ureteroscopic lithotripsy in Galdakao Modified Supine Valdivia position (GMSV) with minimally invasive percutaneous nephrolithotomy (MPCNL) for partial staghorn calculi. METHODS: 67 patients with partial staghorn calculi were randomly divided into two groups. In MPCNL Group, conventional MPCNL was performed in the prone position. In the other group, simultaneous combined MPCNL and flexible ureteroscopic lithotripsy (Endoscopic Combined Intra-Renal Surgery, ECIRS) serves as single session treatment in the GMSV position (ECIRS Group). Demographic, clinical characteristic, perioperative complications and stone free rate (SFR) were recorded. RESULTS: No significant difference was detected between two groups concerning the age, body mass index, hydronephrosis, stone burden and location. The mean operative time was 105.33 +/- 30.28 min in ECIRS group, which is longer (p = 0.002) than MPCNL group (83.58 +/- 24.37 min). The one-step SFR was significantly higher (p = 0.007) in the ECIRS group compared to MPCNL group (87.88% vs 58.82%). The mean blood loss was 77.21 +/- 41.21 ml for ECIRS group and 86.43 +/- 35.61 ml for MPCNL group (p = 0.330). Overall, complication rate is low in both groups. No statistical difference was found in regards to the clinical complications between the two groups (p = 0.409). After the ancillary treatments, the final SFR was 96.97% in ECIRS group and 91.18% in MPCNL group (p = 0.628). CONCLUSION: Simultaneous combined MPCNL and flexible ureteroscopic lithotripsy is an effective and safe treatment for partial staghorn calculi, with significantly higher one-step SFR when compared to conventional MPCNL monotherapy, without additional procedure-related complications. PMID- 26898136 TI - Associations between tongue strength and swallowing difficulty in the older adults receiving long-term care. PMID- 26898137 TI - Detailed Structural and Mechanical Response of Wet Foam to the Settling Particle. AB - Liquid foam, as a complex fluid, provides an observable prototype for studying a discrete fluid system. In this work, a numerical study on the settling behavior of a round particle in wet polydisperse foam has been conducted on the bubble scale. The local and nonuniform distribution of bubble pressure, as well as the localized plastic events, is presented. It shows a foam region of higher pressure in front of the settling particle due to the extrusion deformation of the bubbles applied by the particle. Additionally, the forces exerted on the particle by the disordered wet foam are measured during the sedimentation. It exhibits in particular a power-law dependence of the drag force caused by the bubble as a function of the foam quality. Moreover, sedimentation experiments are demonstrated to verify this power-law relation. The evolution of the components of drag force is demonstrated when a plastic event occurs in front of the settling particle. The result shows that both the contributions of the pulling force of foam films and the bubble pressure to the drag force decrease in that case. Likewise, the variation of both these contributions to the drag force is illustrated as well when a bubble in the wake detaches from the particle. These results assist in understanding the mesoscopic response of wet foam to a settling particle. PMID- 26898138 TI - The Academic Anesthesiologist May Be Classified as an Endangered Species in Japan. PMID- 26898139 TI - Anesthetic Pharmacology in an Oft-Distant Land: What Is Needed for Intravenous Anesthesia in Military Practice? PMID- 26898140 TI - Publishing Trends in Two American Journals in Anesthesiology-Results of an 80 Year Geographical Survey. AB - BACKGROUND: We examined publication trends in two major American journals devoted to anesthesia to understand the geographical distribution of authorship and attempt to decipher the factors that influence this distribution. METHODS: In addition to bibliometric information for all articles published in Anesthesiology between 1941 and 2010 and Anesthesia & Analgesia between 1931 and 2010, we also collected information about the country, continent, and medical school or institution from which the articles were submitted. RESULTS: The top five countries that published research in these journals were the United States, Japan, Germany, Canada, and France. More than 50% of the published articles were submitted from the United States. However, US publications have steadily and significantly declined over the decades. Contributions from Europe and Asia (especially China) have shown marked increases. US spending on research, especially biomedical research, has remained essentially unchanged and declined in some areas, whereas it has increased steadily in some of the other countries we discuss. CONCLUSIONS: There is a significantly increased prominence in publishing from countries other than the United States. The reasons for this include the convenience of Web-based submission, an increased desire by researchers from around the world to publish in journals considered prestigious, English becoming the preferred language of communication amongst academicians in science, the advent of globalization, and a decrease in public research funding in the United States relative to other countries. PMID- 26898141 TI - A History of Intravenous Anesthesia in War (1656-1988). AB - The practice of anesthesia in war places significant restraints on the choice of anesthetic technique used; these include, but are not limited to, safety, simplicity, and portability. Ever since intravenous anesthesia became a practical alternative, there have been military doctors who felt that this technique was particularly suited to this environment. The challenge, as in civilian practice, has been to find the appropriate drugs as well as simple and safe delivery systems. The urgency of war has always stimulated innovation in medicine to counteract the ongoing development of weapons of war and their effects on the human body and to achieve improved survival as public expectations rise. This article traces the development of and the use of intravenous anesthesia by military physicians for battle casualties. The story starts long before the era of modern anesthesia, and the discussion concludes in the dog days of the cold war. The rapidly increasing interest in intravenous anesthesia in both civilian and military practice since the early 1990s is left for other authors to examine. PMID- 26898142 TI - An Examination of Horace Wells' Life as a Manifestation of Major Depressive and Seasonal Affective Disorders. AB - Horace Wells was a Hartford, Connecticut, dentist whose practice flourished because of his clinical skills. He had an imaginative mind that propelled him to the forefront in several aspects of dentistry. Unfortunately, he suffered a recurrent "illness" that began in the winter and resolved in the spring. These symptoms were compatible with both major depressive disorder and seasonal affective disorder as a qualifier. Wells' introduction of nitrous oxide as an anesthetic was also associated with self-inhalation. This led to periods of hypomania, followed by depression. With the progression to ether, then chloroform, there was an episode of mania in January 1848, followed by depression and suicide. PMID- 26898143 TI - Horace Wells and His House on 120 Chambers St in New York City. AB - On January 24, 1848, delirious from chloroform, Horace Wells rushed from his house and office on 120 Chambers St into the street and threw acid on 2 alleged prostitutes. He was arrested and committed to New York's infamous Tombs Prison (currently Manhattan Detention Complex), where he committed suicide. Remodeled and reconstructed, this house, 120 Chambers St, is still standing in Tribeca District. PMID- 26898144 TI - IDH2 deficiency impairs mitochondrial function in endothelial cells and endothelium-dependent vasomotor function. AB - Mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDH2) plays an essential role protecting cells against oxidative stress-induced damage. A deficiency in IDH2 leads to mitochondrial dysfunction and the production of reactive oxygen species (ROS) in cardiomyocytes and cancer cells. However, the function of IDH2 in vascular endothelial cells is mostly unknown. In this study the effects of IDH2 deficiency on mitochondrial and vascular function were investigated in endothelial cells. IDH2 knockdown decreased the expression of mitochondrial oxidative phosphorylation (OXPHOS) complexes I, II and III, which lead to increased mitochondrial superoxide. In addition, the levels of fission and fusion proteins (Mfn-1, OPA-1, and Drp-1) were significantly altered and MnSOD expression also was decreased by IDH2 knockdown. Furthermore, knockdown of IDH2 decreased eNOS phosphorylation and nitric oxide (NO) concentration in endothelial cells. Interestingly, treatment with Mito-TEMPO, a mitochondrial specific superoxide scavenger, recovered mitochondrial fission-fusion imbalance and blunted mitochondrial superoxide production, and reduced the IDH2 knockdown induced decrease in MnSOD expression, eNOS phosphorylation and NO production in endothelial cells. Endothelium-dependent vasorelaxation was impaired, and the concentration of bioavailable NO decreased in the aortic ring in IDH2 knockout mice. These findings suggest that IDH2 deficiency induces endothelial dysfunction through the induction of dynamic mitochondrial changes and impairment in vascular function. PMID- 26898145 TI - Regulation of myokine expression: Role of exercise and cellular stress. AB - Exercise training is well known to improve physical fitness and to combat chronic diseases and aging related disorders. Part of this is thought to be mediated by myokines, muscle derived secretory proteins (mainly cytokines) that elicit auto/paracrine but also endocrine effects on organs such as liver, adipose tissue, and bone. Today, several hundred potential myokines have been identified most of them not exclusive to muscle cells. Strenuous exercise is associated with increased production of free radicals and reactive oxidant species (ROS) as well as endoplasmic reticulum (ER)-stress which at an excessive level can lead to muscle damage and cell death. On the other hand, transient elevations in oxidative and ER-stress are thought to be necessary for adaptive improvements by regular exercise through a hormesis action termed mitohormesis since mitochondria are essential for the generation of energy and tightly connected to ER- and oxidative stress. Exercise induced myokines have been identified by various in vivo and in vitro approaches and accumulating evidence suggests that ROS and ER stress linked pathways are involved in myokine induction. For example, interleukin (IL)-6, the prototypic exercise myokine is also induced by oxidative and ER-stress. Exercise induced expression of some myokines such as irisin and meteorin-like is linked to the transcription factor PGC-1alpha and apparently not related to ER-stress whereas typical ER-stress induced cytokines such as FGF-21 and GDF-15 are not exercise myokines under normal physiological conditions. Recent technological advances have led to the identification of numerous potential new myokines but for most of them regulation by oxidative and ER-stress still needs to be unraveled. PMID- 26898147 TI - Mass spectrometry: Innovation and application--Part VIII. PMID- 26898146 TI - Yeast mitochondrial glutathione is an essential antioxidant with mitochondrial thioredoxin providing a back-up system. AB - Glutathione is an abundant, low-molecular-weight tripeptide whose biological importance is dependent upon its redox-active free sulphydryl moiety. Its role as the main determinant of thiol-redox control has been challenged such that it has been proposed to play a crucial role in iron-sulphur clusters maturation, and only a minor role in thiol redox regulation, predominantly as a back-up system for the cytoplasmic thioredoxin system. Here, we have tested the importance of mitochondrial glutathione in thiol-redox regulation. Glutathione reductase (Glr1) is an oxidoreductase which converts oxidized glutathione to its reduced form. Yeast Glr1 localizes to both the cytosol and mitochondria and we have used a Glr1(M1L) mutant that is constitutively localized to the cytosol to test the requirement for mitochondrial Glr1. We show that the loss of mitochondrial Glr1 specifically accounts for oxidant sensitivity of a glr1 mutant. Loss of mitochondrial Glr1 does not influence iron-sulphur cluster maturation and we have used targeted roGFP2 fluorescent probes to show that oxidant sensitivity is linked to an altered redox environment. Our data indicate mitochondrial glutathione is crucial for mitochondrial thiol-redox regulation, and the mitochondrial thioredoxin system provides a back-up system, but cannot bear the redox load of the mitochondria on its own. PMID- 26898149 TI - Determination of polydimethylsiloxane-water partition coefficients for ten 1 chloro-4-[2,2,2-trichloro-1-(4-chlorophenyl)ethyl]benzene-related compounds and twelve polychlorinated biphenyls using gas chromatography/mass spectrometry. AB - Polymer-water partition coefficients (Kpw) of ten DDT-related compounds were determined in pure water at 25 degrees C using commercial polydimethylsiloxane coated optical fiber. Analyte concentrations were measured by thermal desorption gas chromatography/full scan mass spectrometry (TD-GC/MSFS; fibers) and liquid injection-gas chromatography/selected ion monitoring mass spectrometry (LI GC/MSSIM; water). Equilibrium was approached from two directions (fiber uptake and depletion) as a means of assessing data concordance. Measured compound specific log Kpw values ranged from 4.8 to 6.1 with an average difference in log Kpw between the two approaches of 0.05 log units (~ 12% of Kpw). Comparison of the experimentally-determined log Kpw values with previously published data confirmed the consistency of the results and the reliability of the method. A second experiment was conducted with the same ten DDT-related compounds and twelve selected PCB (polychlorinated biphenyl) congeners under conditions characteristic of a coastal marine field site (viz., seawater, 11 degrees C) that is currently under investigation for DDT and PCB contamination. Equilibration at lower temperature and higher ionic strength resulted in an increase in log Kpw for the DDT-related compounds of 0.28-0.49 log units (61-101% of Kpw), depending on the analyte. The increase in Kpw would have the effect of reducing by approximately half the calculated freely dissolved pore-water concentrations (Cfree). This demonstrates the importance of determining partition coefficients under conditions as they exist in the field. PMID- 26898148 TI - Lysozyme fractionation from egg white at pilot scale by means of tangential flow membrane adsorbers: Investigation of the flow conditions. AB - The application of membrane adsorbers instead of classical packed bed columns for protein fractionation is still a growing field. In the case of egg white protein fractionation, the application of classical chromatography is additionally limited due to its high viscosity that impairs filtration. By using tangential flow membrane adsorbers as stationary phase this limiting factor can be left out, as they can be loaded with particle containing substrates. The flow conditions existing in tangential flow membrane adsorbers are not fully understood yet. Thus, the aim of the present study was to gain a deeper understanding of the transport mechanisms in tangential flow membrane adsorbers. It was found that loading in recirculation mode instead of single pass mode increased the binding capacity (0.39 vs. 0.52 mg cm(-2)). Further, it was shown that either higher flow rates (0.39 mg cm(-2) vs. 0.57 mg cm(-2) at 1 CV min(-1) or 20 CV min(-1), respectively) or higher amounts of the target protein in the feed (0.24 mg cm(-2) vs. 0.85 mg cm(-2) for 2.5 or 39.0 g lysozyme, respectively) led to more protein binding. These results show that, in contrast to radial flow or flat sheet membrane adsorbers, the transport in tangential flow membrane adsorbers is not purely based on convection, but on a mix of convection and diffusion. Additionally, investigations concerning the influence of fouling formation were performed that can lead to transport limitations. It was found that this impact is neglectable. It can be concluded that the usage of tangential flow membrane adsorbers is very recommendable for egg white protein fractionations, although the transport is partly diffusion-limited. PMID- 26898151 TI - Source, impact and removal of malodour from soiled clothing. AB - Static headspace--multi-capillary column--gas chromatography--ion mobility spectrometry (SHS-MCC-GC-IMS) has been applied to the analysis of malodour compounds from soiled clothing (socks and T-shirts), pre- and post washing, at low temperature (20 degrees C). Six volatile compounds (VCs) (i.e. butyric acid, dimethyl disulfide, dimethyl trisulfide, 2-heptanone, 2-nonanone and 2-octanone) were identified. After sensory evaluation of soiled garments they were subjected to laundering with non-perfumed washing powder. The efficiency of the laundering process was evaluated by determining the reduction of each detected volatile compound (VC) post-wash (damp) for socks and T-shirts; VC concentration reductions of between 16 and 100% were noted, irrespective of sample type. Additionally the T-shirt study considered the change in VC concentration post wash (dry) i.e. after the drying process at ambient temperature. Overall VC concentration reductions of between 25 and 98% were noted for T-shirt samples pre wash to post-wash (dry). Finally, a potential biochemical metabolic pathway for the formation of malodour compounds associated with bacteria in axillary sweat is proposed. PMID- 26898150 TI - Quantification of ecdysteroids and retinoic acids in whole daphnids by liquid chromatography-triple quadrupole mass spectrometry. AB - Quantification of ecdysteroids and retinoic acids at picograms per individual is typically achieved with radioimmunoassay methods. However, those methods cannot identify individual types of ecdysteroids or provide an absolute concentration, which poses problems for comparative assays such as the metabolic profiling approach for toxicity testing. The method described in the present paper, based on liquid chromatography-electrospray ionization-triple quadrupole mass spectrometry, was developed to allow the quantification in whole daphnids extracts of ecdysteroids (20-hydroxyecdysone, ecdysone, ponasterone A) and retinoic acid (sum of isomers). This approach avoids having to perform the difficult task of sampling the haemolymph on small organism (<5mm). Recoveries, evaluated at three concentrations in matrix blank fortified samples, ranged from 83 to 119% for ecdysteroids and from 144 to 155% for retinoic acids. Precision (2.4-14.2%) and accuracy (-41.7 to 14.5%) were reproducible and stable over three quality control concentrations. The described liquid chromatography-triple quadrupole mass spectrometry method achieved quantification limits ranging from 210 to 380 pg mL(-1) for ecdysteroids and 5 ng mL(-1) for retinoic acids in spiked matrix blanks. 20-hydroxyecdysone was quantified in Daphnia magna adults (19 +/- 8 pg ind(-1)) and juveniles (3.6 +/- 1.0 pg ind(-1)), but was below the limit of quantification in neonates (~ 0.19 pg ind(-1)). Ecdysone was also detected in adult specimens (~ 1.8 pg ind(-1)). PMID- 26898152 TI - Effect of nano-sized, elemental selenium supplement on the proteome of chicken liver. AB - The nano-sized (100-500 nm) selenium has higher bioavailability and relatively lower toxicity compared to other selenium forms. The objective of the present study was to compare liver proteome profiles of broiler chicken fed with control diet without Se supplementation and diet supplemented with nano-Se with 4.25 mg/kg DM. Differential proteome analyses were performed by two-dimensional gel electrophoresis (2D-PAGE) followed by tryptic digestion and protein identification by liquid chromatography-mass spectrometry (LC-MS). Seven hundred and eight spots were detected, and 18 protein spots showed significant difference in their intensity (p < 0.05) between the two groups. In response to nano-Se supplementation, the expression of 8 proteins was higher, and 5 proteins were lower in nano-Se supplemented group compared to control group. The functions of the differentially expressed proteins indicate that the high dose of selenium supplementation induced a dietary stress. Selenium supplementation may influence the metabolism of fatty acids and carbohydrates and antioxidant system, and increase the quantity of cytoskeletal actin and the expression of actin regulatory protein as well. PMID- 26898154 TI - The design of 3D artificial leaves with spatially separated active sites for H2 and O2 generation and their application to water splitting. AB - In this study, we report a facile, environmentally friendly sol-gel route for the preparation of 3D TiO2 artificial leaves with spatially separated active sites for H2 and O2 generation. The unique CoOx/TiO2/Pt architecture has multiple merits and exhibits enhanced photocatalytic activity for hydrogen production. PMID- 26898153 TI - Influence of selected plant amines on probing behaviour of bird cherry-oat aphid (Rhopalosiphum padi L.). AB - The study aimed to quantify the influence of common plant polyamines and tyramine on probing behaviour in the bird cherry-oat aphid (Rhopalosiphum padi L.). Electrical penetration graphs (DC) were used to monitor the probing and feeding behaviour of R. padi exposed to the amines agmatine, cadaverine, putrescine, spermidine, spermine and tyramine. The study results showed that the analyzed amines tended to shorten the stylet activity of aphids in the gels (as indicated by the g-C pattern), prolong the duration of non-probing behaviour (g-np pattern) and decrease salivation into the gels (g-E1pattern) and ingestion from the gels (g-G pattern). The 10 mM concentration of the studied amines, especially cadaverine, reduced or completely inhibited aphid ingestion. The obtained results demonstrate that plant amines participate in plant defence responses to R. padi through disturbance of its probing behaviour and the intensity of such effects is concentration dependent. PMID- 26898155 TI - Viruliferous rate of small brown planthopper is a good indicator of rice stripe disease epidemics. AB - Rice stripe virus (RSV), its vector insect (small brown planthopper, SBPH) and climatic conditions in Jiangsu, China were monitored between 2002 and 2012 to determine key biotic and abiotic factors driving epidemics of the disease. Average disease severity, disease incidence and viruliferous rate of SBPH peaked in 2004 and then gradually decreased. Disease severity of RSV was positively correlated with viruliferous rate of the vector but not with the population density of the insect, suggesting that the proportion of vectors infected by the virus rather than the absolute number of vectors plays an important role in RSV epidemics and could be used for disease forecasting. The finding of a positive correlation of disease severity and viruliferous rate among years suggests that local infection is likely the main source of primary inoculum of RSV. Of the two main climatic factors, temperature plays a more important role than rainfall in RSV epidemics. PMID- 26898156 TI - Measurement of glycated albumin in serum and plasma by LC-MS/MS. AB - BACKGROUND: Diagnosis of diabetes and monitoring of long-term blood sugar are preferably done by measurement of glycated hemoglobin (HbA1c). Diabetic patients with end stage renal disease (ESRD) may have short-lived red blood cells due to hemodialysis (HD), and thus higher turnover of hemoglobin. The level of glycated hemoglobin (HbA1c) may be lower than expected for these patients, even at increased blood glucose, possibly making glycated albumin (GA) measurement a better alternative. METHODS: The percentage of GA was measured by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Fast and efficient trypsin digestion of proteins in diluted serum or plasma resulted in a high number of proteotypic peptides from albumin, including KQTALVELVK which was detected both glycated and non-glycated by multiple reaction monitoring (MRM). The percentage of GA was estimated by neat peak area response of glycated peptide divided by the sum of glycated and non-glycated peptide. RESULTS: Acceptable method reproducibility (6% CV), repeatability (2-6% CV), limit of quantification (0.75% GA), linearity (R(2) = 0.999) and recovery (79 +/- 9%) was achieved without using calibration or isotope-labeled internal standard. GA was strongly correlated with HbA1c (r = 0.84) for patients without ESRD. The average ratio of GA/HbA1c was significantly higher (p = 0.0021) for ESRD patients (1.84 +/- 0.38, n = 62) compared to other patients (1.67 +/- 0.28, n = 225). CONCLUSION: GA measurement by detecting glycation in KQTALVELVK with LC-MS/MS seems to be a useful supplement to HbA1c for detecting increased blood glucose in diabetic patients with ESRD. PMID- 26898157 TI - Intracanal irrigants for pulpectomy in primary teeth: a systematic review and meta-analysis. AB - OBJECTIVE: To conduct a systematic review and meta-analysis to assess the findings on the clinical efficacy of intracanal irrigants employed during pulpectomy of primary teeth. METHODS: A systematic search was performed in electronic databases and peer-reviewed paediatric dentistry journals to find relevant studies. Titles, abstracts, and full-text papers were located, screened, and assessed independently by two reviewers, and a meta-analysis was performed. RESULTS: The search identified a total of 775 records; 46 were selected and reviewed in full text. After screening, seven studies met the eligibility criteria for inclusion. Three studies compared the 2% chlorhexidine and saline solutions, but no analysis could be performed because of the heterogeneity between these; two of the studies reported non-comparative methodologies and results when compared, and were not analysed. Finally, two studies compared a mixture of tetracycline isomer, an acid, and a detergent (MTDA) or oxidative potential water (OPW) to sodium hypochlorite (NaOCl), without showing significant heterogeneity; therefore, their combined outcomes were included. Both fixed and random mixed models resulted in a non-significant weighted mean difference between treatments, according to a forest plot. CONCLUSIONS: More studies are required with adequate quality, as well as a full-result report, including summary measurements of both response variables and effect size, to determine the most effective irrigant agents for use in pulpectomies. PMID- 26898158 TI - Sofosbuvir and ledipasvir for HIV/HCV co-infected patients. AB - INTRODUCTION: Hepatitis C virus (HCV) is a chronic infection that disproportionately impacts people living with HIV. In the past, HCV therapy was less effective in individuals with HIV co-infection. However, the advent of direct-acting antivirals has revolutionized HCV treatment with high rates of success in patients both with and without HIV. AREAS COVERED: In this paper, we review the evidence supporting the use of ledipasvir and sofosbuvir (LDV/SOF) for the treatment of HCV in patients with HIV co-infection. Articles searchable on MEDLINE/PubMed were reviewed to provide context for use of LDV/SOF in individuals with HCV and HIV co-infection. EXPERT OPINION: This treatment is highly effective in achieving HCV cure or sustained virologic response, however further studies need to done to address efficacy of treatment in people with uncontrolled HIV, concerns regarding drug-interactions with antiretroviral therapy, and potential for shorter duration treatment. PMID- 26898159 TI - Selection of suitable fertilizer draw solute for a novel fertilizer-drawn forward osmosis-anaerobic membrane bioreactor hybrid system. AB - In this study, a protocol for selecting suitable fertilizer draw solute for anaerobic fertilizer-drawn forward osmosis membrane bioreactor (AnFDFOMBR) was proposed. Among eleven commercial fertilizer candidates, six fertilizers were screened further for their FO performance tests and evaluated in terms of water flux and reverse salt flux. Using selected fertilizers, bio-methane potential experiments were conducted to examine the effect of fertilizers on anaerobic activity due to reverse diffusion. Mono-ammonium phosphate (MAP) showed the highest biogas production while other fertilizers exhibited an inhibition effect on anaerobic activity with solute accumulation. Salt accumulation in the bioreactor was also simulated using mass balance simulation models. Results showed that ammonium sulfate and MAP were the most appropriate for AnFDFOMBR since they demonstrated less salt accumulation, relatively higher water flux, and higher dilution capacity of draw solution. Given toxicity of sulfate to anaerobic microorganisms, MAP appears to be the most suitable draw solution for AnFDFOMBR. PMID- 26898160 TI - Mechanistic investigation in ultrasound induced enhancement of enzymatic hydrolysis of invasive biomass species. AB - This study has assessed four invasive weeds, viz. Saccharum spontaneum (SS), Mikania micrantha (MM), Lantana camara (LC) and Eichhornia crassipes (EC) for enzymatic hydrolysis prior to bioalcohol fermentation. Enzymatic hydrolysis of pretreated biomasses of weeds has been conducted with mechanical agitation and sonication under constant (non-optimum) conditions. Profiles of total reducible sugar release have been fitted to HCH-1 model of enzymatic hydrolysis using Genetic Algorithm. Trends in parameters of this model reveal physical mechanism of ultrasound-induced enhancement of enzymatic hydrolysis. Sonication accelerates hydrolysis kinetics by ~10-fold. This effect is contributed by several causes, attributed to intense micro-convection generated during sonication: (1) increase in reaction velocity, (2) increase in enzyme-substrate affinity, (3) reduction in product inhibition, and (4) enhancement of enzyme activity due to conformational changes in its secondary structure. Enhancement effect of sonication is revealed to be independent of conditions of enzymatic hydrolysis - whether optimum or non optimum. PMID- 26898161 TI - Polyamines regulate cell growth and cellular methylglyoxal in high-glucose medium independently of intracellular glutathione. AB - Polyamines can presumably inhibit protein glycation, when associated with the methylglyoxal inevitably produced during glycolysis. Herein, we hypothesized a nonenzymatic interaction between putrescine and methylglyoxal in putrescine deficient or -overexpressing Dictyostelium cells in high-glucose medium, which can control methylglyoxal production. Putrescine was essentially required for growth rescue accompanying methylglyoxal detoxification when cells underwent growth defect and cell cycle G1-arrest when supplemented with high glucose. Furthermore, methylglyoxal regulation by putrescine seemed to be a parallel pathway independent of the changes in cellular glutathione content in high glucose medium. Consequently, we suggest that Dictyostelium cells need polyamines for normal growth and cellular methylglyoxal regulation. PMID- 26898162 TI - Eco-evolutionary dynamics in a coevolving host-virus system. AB - Eco-evolutionary dynamics have been shown to be important for understanding population and community stability and their adaptive potential. However, coevolution in the framework of eco-evolutionary theory has not been addressed directly. Combining experiments with an algal host and its viral parasite, and mathematical model analyses we show eco-evolutionary dynamics in antagonistic coevolving populations. The interaction between antagonists initially resulted in arms race dynamics (ARD) with selective sweeps, causing oscillating host-virus population dynamics. However, ARD ended and populations stabilised after the evolution of a general resistant host, whereas a trade-off between host resistance and growth then maintained host diversity over time (trade-off driven dynamics). Most importantly, our study shows that the interaction between ecology and evolution had important consequences for the predictability of the mode and tempo of adaptive change and for the stability and adaptive potential of populations. PMID- 26898163 TI - Painful Issues in Pain Prediction. AB - How perception of pain emerges from neural activity is largely unknown. Identifying a neural 'pain signature' and deriving a way to predict perceived pain from brain activity would have enormous basic and clinical implications. Researchers are increasingly turning to functional brain imaging, often applying machine-learning algorithms to infer that pain perception occurred. Yet, such sophisticated analyses are fraught with interpretive difficulties. Here, we highlight some common and troublesome problems in the literature, and suggest methods to ensure researchers draw accurate conclusions from their results. Since functional brain imaging is increasingly finding practical applications with real world consequences, it is critical to interpret brain scans accurately, because decisions based on neural data will only be as good as the science behind them. PMID- 26898164 TI - Lamellar Macular Hole: Two Distinct Clinical Entities? AB - PURPOSE: To investigate whether lamellar macular holes can be divided into different subgroups. DESIGN: Retrospective observational case series. METHODS: In this institutional study, clinical charts and spectral-domain optical coherence tomography (OCT) images of 102 eyes of 90 consecutive patients diagnosed with lamellar macular hole were reviewed. In OCT imaging, the presence of lamellar macular hole was defined according to the following findings: presence of irregular foveal contour, separation of the layers of the neurosensory retina, and the absence of full-thickness macular defect. Mean outcome was the morphologic and functional characterization of different subtypes of macular hole. RESULTS: Two different subtypes of lamellar macular hole were identified: tractional and degenerative. The first type, tractional, was diagnosed in 43 eyes, and was characterized by the schitic separation of neurosensory retina between outer plexiform and outer nuclear layers. It often presented with an intact ellipsoid layer and was associated with tractional epiretinal membranes and/or vitreomacular traction. The second type, degenerative, was diagnosed in 48 eyes, and its distinctive traits included the presence of intraretinal cavitation that could affect all retinal layers. It was often associated with nontractional epiretinal proliferation and a retinal "bump." Moreover, it often presented with early ellipsoidal zone defect and its pathogenesis, although chronic and progressive, remains poorly understood. Eleven eyes shared common features with both tractional and degenerative lamellar macular holes and were classified as mixed lesions. CONCLUSIONS: Degenerative and tractional lamellar macular holes may be 2 distinct clinical entities. A revision of the current concept of lamellar macular holes is needed. PMID- 26898166 TI - Red ginseng and vitamin C increase immune cell activity and decrease lung inflammation induced by influenza A virus/H1N1 infection. AB - OBJECTIVES: Because red ginseng and vitamin C have immunomodulatory function and anti-viral effect, we investigated whether red ginseng and vitamin C synergistically regulate immune cell function and suppress viral infection. METHODS: Red ginseng and vitamin C were treated to human peripheral blood mononuclear cells (PBMCs) or sarcoma-associated herpesvirus (KSHV)-infected BCBL 1, and administrated to Gulo(-/-) mice, which are incapable of synthesizing vitamin C, with or without influenza A virus/H1N1 infection. KEY FINDINGS: Red ginseng and vitamin C increased the expression of CD25 and CD69 of PBMCs and natural killer (NK) cells. Co-treatment of them decreased cell viability and lytic gene expression in BCBL-1. In Gulo(-/-) mice, red ginseng and vitamin C increased the expression of NKp46, a natural cytotoxic receptor of NK cells and interferon (IFN)-gamma production. Influenza infection decreased the survival rate, and increased inflammation and viral plaque accumulation in the lungs of vitamin C-depleted Gulo(-/-) mice, which were remarkably reduced by red ginseng and vitamin C supplementation. CONCLUSIONS: Administration of red ginseng and vitamin C enhanced the activation of immune cells like T and NK cells, and repressed the progress of viral lytic cycle. It also reduced lung inflammation caused by viral infection, which consequently increased the survival rate. PMID- 26898167 TI - Consumption of cosmetic products by the French population second part: Amount data. AB - The aim of the study was to assess the amount per use of cosmetic products consumed at home by the adult, child and baby French population. 1078 men and women participated in the study which was performed in four cities of France. This enquiry was performed on 106 cosmetics including general hygiene, skin care, hair care, hair styling, make-up, fragrances, solar, shaving and depilatory, and baby products. Coupled to frequency data previously obtained (Ficheux et al., 2015), these amounts per use data will be used in order to assess the exposure to cosmetics by the French population. These current exposure values could be useful for safety assessors and for safety agencies. PMID- 26898165 TI - Traumatic Brain Injury Causes Aberrant Migration of Adult-Born Neurons in the Hippocampus. AB - Traumatic brain injury (TBI) promotes neural stem/progenitor cell (NSC) proliferation in an attempt to initiate innate repair mechanisms. However, all immature neurons in the CNS are required to migrate from their birthplace to their final destination to develop into functional neurons. Here we assessed the destination of adult-born neurons following TBI. We found that a large percentage of immature neurons migrated past their normal stopping site at the inner granular cell layer (GCL), and became misplaced in the outer GCL of the hippocampal dentate gyrus. The aberrant migration of adult-born neurons in the hippocampus occurred 48 hours after TBI, and lasted for 8 weeks, resulting in a great number of newly generated neurons misplaced in the outer GCL in the hippocampus. Those misplaced neurons were able to become mature and differentiate into granular neurons, but located ectopically in the outer GCL with reduced dendritic complexity after TBI. The adult-born neurons at the misplaced position may make wrong connections with inappropriate nearby targets in the pre-existing neural network. These results suggest that although stimulation of endogenous NSCs following TBI might offer new avenues for cell-based therapy, additional intervention is required to further enhance successful neurogenesis for repairing the damaged brain. PMID- 26898168 TI - The prognostic value of sentinel lymph node micrometastases in patients with invasive breast carcinoma. AB - AIM: The prognostic value of sentinel lymph node micrometastases in invasive breast cancer patients is still widely debated. Even if, in the absence of unequivocal guidelines, the axillary lynphadenectomy is not still performed in the routine clinical care of these patients. METHOD: We have retrospectively analyzed 746 patients with operable invasive breast cancer and clinically negative axillary lymph nodes. These patients underwent conservative surgery or total mastectomy with sentinel lymph node biopsy. Patients with micrometastases in the sentinel lymph node treated with axillary dissection has been checked and the involvement of the remaining lymph nodes analyzed. Patients with micrometastases in the SLN not followed by axillary dissection have been checked as well and the incidence of recurrences has been evaluated in both groups. RESULTS: Micrometastases were found in 51 (6.83%) patients and isolated tumor cells in 8 (1.07%) patients at frozen section and confirmed at the final hystopathologic examination. Fifteen of these patients underwent complete axillary dissection: two of them (13.33%) had metastatic involvement of other axillary lymph nodes. The other 44 patients didn't receive further surgical axillary procedure. No axillary recurrences in these patients were found during a median follow up of 65.3+/-9.65 months (range 42-78 months). CONCLUSION: Based on the results and according to some recent randomized trials we can say that axillary lynphadenectomy can be avoided when micrometastases are found in sentinel lynph nodes. It should be performed anyway, depending on the analysis of the biomedical profile of the tumor. KEY WORDS: Breast carcinoma, Micrometases, Sentinel lymph node. PMID- 26898169 TI - K4[Fe(CN)6] immobilized anion sensitive protonated amine functionalized polysilsesquioxane films for ultra-low electrochemical detection of dsDNA. AB - Charge transport in polymeric films bound by redox reagents is a topic of current interest. The dynamics of electroinactive ions across the interface is studied by immobilizing ferrocyanide anion in a polysilsesquioxanes (PSQs) modified electrode. Redox reagents can stay in the polymeric film by either physical forces or electrostatic binding. The present work describes the immobilization of ferro/ferricyanide redox couples in PSQ films possessing protonated amine functional groups by electrostatic interactions. Charge transport in [Fe(CN)6](4 )-PSQs film was found to be anion dependent, and its formal potential value varied with the relative hydrophilic or hydrophobic nature of the anion used in the supporting electrolyte, unlike the observed dependence on solution cation for electrodes modified with metal hexacyanoferrates (Prussian Blue analogues). The [Fe(CN)6](4-) bound PSQs films were extensively characterized by varying different supporting electrolytes anions using cyclic voltammetry. The redox peak currents were linearly proportional to the square root of the scan rate, implying that the transport of charge carriers is accompanied with redox ion diffusion and electron hopping in a confined space. dsDNA molecules were found to interact with this polymer matrix through anionic phosphate groups. Both voltammetry and A.C. impedance spectroscopy studies revealed that these interactions could be exploited for the determination of ultra-low level (0.5 attomolar) of dsDNA present in aqueous solution. PMID- 26898170 TI - Inter-Strain Differences in Default Mode Network: A Resting State fMRI Study on Spontaneously Hypertensive Rat and Wistar Kyoto Rat. AB - Genetic divergences among mammalian strains are presented phenotypically in various aspects of physical appearance such as body shape and facial features. Yet how genetic diversity is expressed in brain function still remains unclear. Functional connectivity has been shown to be a valuable approach in characterizing the relationship between brain functions and behaviors. Alterations in the brain default mode network (DMN) have been found in human neuropsychological disorders. In this study we selected the spontaneously hypertensive rat (SHR) and the Wistar Kyoto rat (WKY), two inbred rat strains with close genetic origins, to investigate variations in the DMN. Our results showed that the major DMN differences are the activities in hippocampal area and caudate putamen region. This may be correlated to the hyperactive behavior of the SHR strain. Advanced animal model studies on variations in the DMN may have potential to shed new light on translational medicine, especially with regard to neuropsychological disorders. PMID- 26898171 TI - Recurrent giant cell fibroblastoma: Malignancy predisposition in Kabuki syndrome revisited. AB - Kabuki syndrome is a genetic condition characterized by distinctive facial phenotype, mental retardation, and internal organ malformations. Mutations of the epigenetic genes KMT2D and KDM6A cause dysregulation of certain developmental genes and account for the multiple congenital anomalies of the syndrome. Eight cases of malignancies have been reported in young patients with Kabuki syndrome although a causative association to the syndrome has not been established. We report a case of a 12-year-old girl with Kabuki syndrome who developed a tumor on the right side of her neck. A relapsing tumor 19 months after initial excision, proved to be giant cell fibroblastoma. Tauhis is the first report of giant cell fibroblastoma -a rare tumor of childhood- in a patient with Kabuki syndrome. PMID- 26898172 TI - Burning and graphitization of optically levitated nanodiamonds in vacuum. AB - A nitrogen-vacancy (NV(-)) centre in a nanodiamond, levitated in high vacuum, has recently been proposed as a probe for demonstrating mesoscopic centre-of-mass superpositions and for testing quantum gravity. Here, we study the behaviour of optically levitated nanodiamonds containing NV(-) centres at sub-atmospheric pressures and show that while they burn in air, this can be prevented by replacing the air with nitrogen. However, in nitrogen the nanodiamonds graphitize below ~10 mB. Exploiting the Brownian motion of a levitated nanodiamond, we extract its internal temperature (T(i)) and find that it would be detrimental to the NV(-) centre's spin coherence time. These values of T(i) make it clear that the diamond is not melting, contradicting a recent suggestion. Additionally, using the measured damping rate of a levitated nanoparticle at a given pressure, we propose a new way of determining its size. PMID- 26898174 TI - Induced smectic phases of stoichiometric liquid crystal mixtures. AB - We revealed the detailed structures of induced smectic liquid crystal (LC) phases composed of a binary mixture of charge-transfer (CT) LC substances. Although neither of the constituents had highly ordered smectic phases, the mixture exhibited smectic-E (SmE) or smectic-B (SmB) phases when mixed at ratios of 1 : 1 and 2 : 3, respectively. The results of polarized optical microscopy, differential scanning calorimetry, X-ray diffraction, and infrared spectroscopy indicated that the induced smectic phases were stabilized by an exquisite balance between the CT interactions, dipolar interactions, and excluded volume effects. We proposed a possible model for the molecular arrangements in the SmE and SmB phases, which consistently explained the experimental results including the stoichiometric ratios. PMID- 26898173 TI - Detecting gas-induced vasomotor changes via blood oxygenation level-dependent contrast in healthy breast parenchyma and breast carcinoma. AB - PURPOSE: To evaluate blood oxygenation level-dependent (BOLD) contrast changes in healthy breast parenchyma and breast carcinoma during administration of vasoactive gas stimuli. MATERIALS AND METHODS: Magnetic resonance imaging (MRI) was performed at 3T in 19 healthy premenopausal female volunteers using a single shot fast spin echo sequence to acquire dynamic T2 -weighted images. 2% (n = 9) and 5% (n = 10) carbogen gas mixtures were interleaved with either medical air or oxygen in 2-minute blocks, for four complete cycles. A 12-minute medical air breathing period was used to determine background physiological modulation. Pixel wise correlation analysis was applied to evaluate response to the stimuli in breast parenchyma and these results were compared to the all-air control. The relative BOLD effect size was compared between two groups of volunteers scanned in different phases of the menstrual cycle. The optimal stimulus design was evaluated in five breast cancer patients. RESULTS: Of the four stimulus combinations tested, oxygen vs. 5% carbogen produced a response that was significantly stronger (P < 0.05) than air-only breathing in volunteers. Subjects imaged during the follicular phase of their cycle when estrogen levels typically peak exhibited a significantly smaller BOLD response (P = 0.01). Results in malignant tissue were variable, with three out of five lesions exhibiting a diminished response to the gas stimulus. CONCLUSION: Oxygen vs. 5% carbogen is the most robust stimulus for inducing BOLD contrast, consistent with the opposing vasomotor effects of these two gases. Measurements may be confounded by background physiological fluctuations and menstrual cycle changes. J. Magn. Reson. Imaging 2016;44:335-345. PMID- 26898175 TI - Acetylated Trivalent Mannobioses: Chemical Modification, Structural Elucidation, and Biological Evaluation. AB - People suffering from allergies can be treated with repeated injections of increasing amounts of a specific allergen. This type of specific immunotherapy is currently the only way to treat the underlying pathological immune response associated with an allergy. The approach can afford long-lasting protection, but the process takes 3-5 years, can produce allergic reactions, and in severe cases treatment is often aborted due to anaphylaxis. However, treatment can be optimized with the use of specific adjuvants that modify the immune response, its duration, and that increase the production of the correct type of antibodies. In the pursuit of such adjuvants, two new trivalent acetylated beta-(1->2)-linked mannobioses based on a previously discovered lead molecule were prepared. The new molecules, along with the previously developed lead, were investigated by rigorous NMR and molecular modeling experiments in order to elucidate their behavior and preferred conformations in solution. Furthermore, the molecules were subjected to a biological investigation in which their immunostimulatory properties were evaluated by assessing their effect on the production of TH 2 type cytokine interleukin-4 (IL-4) and Treg pro-inflammatory cytokine tumor necrosis factor (TNF). Treatment of peripheral mononuclear blood cell cultures from patients suffering from birch allergy with birch allergen Bet v induced a strong IL-4 response, whereas the same treatment together with the trivalent acetylated mannobioses caused significant suppression of the induced IL-4. PMID- 26898176 TI - Multi-target-qubit unconventional geometric phase gate in a multi-cavity system. AB - Cavity-based large scale quantum information processing (QIP) may involve multiple cavities and require performing various quantum logic operations on qubits distributed in different cavities. Geometric-phase-based quantum computing has drawn much attention recently, which offers advantages against inaccuracies and local fluctuations. In addition, multiqubit gates are particularly appealing and play important roles in QIP. We here present a simple and efficient scheme for realizing a multi-target-qubit unconventional geometric phase gate in a multi cavity system. This multiqubit phase gate has a common control qubit but different target qubits distributed in different cavities, which can be achieved using a single-step operation. The gate operation time is independent of the number of qubits and only two levels for each qubit are needed. This multiqubit gate is generic, e.g., by performing single-qubit operations, it can be converted into two types of significant multi-target-qubit phase gates useful in QIP. The proposal is quite general, which can be used to accomplish the same task for a general type of qubits such as atoms, NV centers, quantum dots, and superconducting qubits. PMID- 26898177 TI - The search for universal transdiagnostic and trans-therapy change processes: Evidence for intolerance of uncertainty. AB - The search for universal processes associated with symptom change across emotional disorders and different forms of psychotherapy offers hope of increased theoretical parsimony and treatment efficiencies. This study investigated whether intolerance of uncertainty (IU) is a universal process by examining whether changes in IU were associated with changes in symptoms across three different cognitive behavior therapy protocols for depression (n=106), social anxiety disorder (n=88), or generalized anxiety disorder (n=62) in a community mental health clinic. IU was associated with reductions in repetitive negative thinking in all treatments, which is consistent with IU being a transdiagnostic and 'trans therapy' process of change. Changes in IU were also associated with symptom relief in the social anxiety disorder and generalized anxiety disorder groups, but not in the depression group. Implications of these findings are discussed within the broader literature of transdiagnostic approaches to emotional disorders. PMID- 26898178 TI - Characterization of the mechanomyographic signal of three different muscles and at different levels of isometric contractions. AB - PURPOSE: Lateral (X) and longitudinal (Y) mechanical oscillations of muscle fibers that take place during muscular contraction seem to contain information additionally to the myoelectric activity, which can contribute to the interpretation of some muscle gradation force mechanisms. However, no previous study was found that had investigated the relationship between the muscle force and features associated to the mechanomyographic (MMG) signal obtained by means of a biaxial accelerometer in three different muscles. Therefore, the aim of this study was to evaluate the relationship between the force output at different load levels (20% to 100%) of the maximum voluntary isometric contraction (%MVIC) and the two signals supplied by a biaxial accelerometer and, in addition, the so called resultant (R) acceleration signal derived from the two signals mentioned previously. Twenty seven male volunteers participated in this study. METHODS: The force output related to the right biceps brachii, soleus and gastrocnemius medialis muscles was studied by means of linear regression models fit to log transformed of the root mean square (RMS) values of the MMG signals in X, Y, and R axes versus each %MVIC. The phase angle of R acceleration (PhaseR) and anthropometric data were also considered. RESULTS: The angular coefficient a and the antilog of y-intercept b from the log-transformed of MMG data values versus force output were able to distinguish partially motor unit strategies during isometric contractions in the three muscles studied. CONCLUSION: The findings suggest that biaxial accelerometer seems to be an interesting approach in the assessment of muscle contraction properties. PMID- 26898179 TI - Portable microfluidic and smartphone-based devices for monitoring of cardiovascular diseases at the point of care. AB - Cardiovascular diseases (CVDs) are the main causes of morbidity and mortality in the world where about 4 in every 5 CVD deaths happen in low- and middle-income countries (LMICs). Most CVDs are preventable and curable, which is largely dependent on timely and effective interventions, including diagnosis, prognosis and therapeutic monitoring. However, these interventions are high-cost in high income countries and are usually lacking in LMICs. Thanks to the rapid development of microfluidics and nanotechnology, lots of portable analytical devices are developed for detection of CVDs at the point-of-care (POC). In the meantime, smartphone, as a versatile and powerful handheld tool, has been employed not only as a reader for microfluidic assays, but also as an analyzer for physiological indexes. In this review, we present a comprehensive introduction of the current status and potential development direction on POC diagnostics for CVDs. First of all, we introduce some main facts about CVDs and their standard diagnostic procedures and methods. Second, we discuss about both commercially available POC devices and developed prototypes for detection of CVDs via immunoassays. Subsequently, we report the advances in smartphone-based readout for microfluidic assays. Finally, we present some examples using smartphone, individually or combined with other components or devices, for CVD monitoring. We envision an integrated smartphone-based system capable of functioning blood tests, disease examination, and imaging will come in the future. PMID- 26898180 TI - Long 5' untranslated regions regulate the RNA stability of the deep-sea filamentous phage SW1. AB - Virus production in the deep-sea environment has been found to be high, and viruses have been suggested to play significant roles in the overall functioning of this ecosystem. Nevertheless, little is known about these viruses, including the mechanisms that control their production, which makes them one of the least understood biological entities on Earth. Previously, we isolated the filamentous phage SW1, whose virus production and gene transcription were found to be active at low temperatures, from a deep-sea bacterium, Shewanella piezotolerans WP3. In this study, the operon structure of phage SW1 is presented, which shows two operons with exceptionally long 5' and 3' untranslated regions (UTRs). In addition, the 5'UTR was confirmed to significantly influence the RNA stability of the SW1 transcripts. Our study revealed novel regulation of the operon and led us to propose a unique regulatory mechanism for Inoviruses. This type of RNA-based regulation may represent a mechanism for significant viral production in the cold deep biosphere. PMID- 26898182 TI - VAP, a Versatile Access Point for the Endoplasmic Reticulum: Review and analysis of FFAT-like motifs in the VAPome. AB - Dysfunction of VAMP-associated protein (VAP) is associated with neurodegeneration, both Amyotrophic Lateral Sclerosis and Parkinson's disease. Here we summarize what is known about the intracellular interactions of VAP in humans and model organisms. VAP is a simple, small and highly conserved protein on the cytoplasmic face of the endoplasmic reticulum (ER). It is the sole protein on that large organelle that acts as a receptor for cytoplasmic proteins. This may explain the extremely wide range of interacting partners of VAP, with components of many cellular pathways binding it to access the ER. Many proteins that bind VAP also target other intracellular membranes, so VAP is a component of multiple molecular bridges at membrane contact sites between the ER and other organelles. So far approximately 100 proteins have been identified in the VAP interactome (VAPome), of which a small minority have a "two phenylalanines in an acidic tract" (FFAT) motif as it was originally defined. We have analyzed the entire VAPome in humans and yeast using a simple algorithm that identifies many more FFAT-like motifs. We show that approximately 50% of the VAPome binds directly or indirectly via the VAP-FFAT interaction. We also review evidence on pathogenesis in genetic disorders of VAP, which appear to arise from reduced overall VAP levels, leading to ER stress. It is not possible to identify one single interaction that underlies disease. This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon. PMID- 26898184 TI - Solution Behavior of Amphiphilic Glycodendrimers with a Rod-Like Core. AB - Glycodendrimers based on aromatic cores have an amphiphilic character and have been reported to generate supramolecuar assemblies in water. A new group of glycodendrimers with an aromatic rod-like core were recently described as potent antagonists of DC-SIGN-mediated viral infections. A full characterization of the aggregation properties of these materials is presented here. The results show that these compounds exist mostly as monomers in water solution, in dynamic equilibrium with small aggregates (dimers or trimers). Larger aggregates observed by dynamic light scattering and transmission Electron Microscopy for some of the dendrimers are found to be portions of materials not fully solubilized and can be removed either by optimizing the dissolution protocol or by centrifugation of the samples. PMID- 26898185 TI - Use of evidence-based treatments in substance abuse treatment programs serving American Indian and Alaska Native communities. AB - BACKGROUND: Research and health surveillance activities continue to document the substantial disparities in the impacts of substance abuse on the health of American Indian and Alaska Native (AI/AN) people. While Evidence-Based Treatments (EBTs) hold substantial promise for improving treatment for AI/ANs with substance use problems (as they do for non-AI/ANs), anecdotal reports suggest that their use is limited. In this study, we examine the awareness of, attitudes toward, and use of EBTs in substance abuse treatment programs serving AI/AN communities. METHODS: Data are drawn from the first national survey of tribal substance abuse treatment programs. Clinicians or clinical administrators from 192 programs completed the survey. Participants were queried about their awareness of, attitudes toward, and use of 9 psychosocial and 3 medication EBTs. RESULTS: Cognitive Behavioral Therapy (82.2%), Motivational Interviewing (68.6%), and Relapse Prevention Therapy (66.8%) were the most commonly implemented psychosocial EBTs; medications for psychiatric comorbidity was the most commonly implemented medication treatment (43.2%). Greater EBT knowledge and use were associated with both program (e.g., funding) and staff (e.g., educational attainment) characteristics. Only two of the commonly implemented psychosocial EBTs (Motivational Interviewing and Relapse Prevention Therapy) were endorsed as culturally appropriate by a majority of programs that had implemented them (55.9% and 58.1%, respectively). CONCLUSIONS: EBT knowledge and use is higher in substance abuse treatment programs serving AI/AN communities than has been previously estimated. However, many users of these EBTs continue to have concerns about their cultural appropriateness, which likely limits their further dissemination. PMID- 26898181 TI - miRNA regulation of white and brown adipose tissue differentiation and function. AB - Obesity and metabolic disorders are a major health concern in all developed countries and a primary focus of current medical research is to improve our understanding treatment of metabolic diseases. One avenue of research that has attracted a great deal of recent interest focuses upon understanding the role of miRNAs in the development of metabolic diseases. miRNAs have been shown to be dysregulated in a number of different tissues under conditions of obesity and insulin resistance, and have been demonstrated to be important regulators of a number of critical metabolic functions, including insulin secretion in the pancreas, lipid and glucose metabolism in the liver, and nutrient signaling in the hypothalamus. In this review we will focus on the important role of miRNAs in regulating the differentiation and function of white and brown adipose tissue and the potential importance of this for maintaining metabolic function and treating metabolic diseases. This article is part of a Special Issue entitled: MicroRNAs and lipid/energy metabolism and related diseases edited by Carlos Fernandez Hernando and Yajaira Suarez. PMID- 26898186 TI - Network analysis of substance abuse and dependence symptoms. AB - BACKGROUND: The DSM uses one set of abuse and dependence criteria to assess multiple substance use disorders (SUDs). Most SUD research aggregates across these symptoms to study the behavior of SUD as a static construct. We use an alternative approach that conceptualizes symptoms as directly interacting variables in psychopathological networks. We apply network models to symptom level data to investigate the unique roles of individual symptoms and their interactions in SUD. METHODS: We analyzed 11 DSM III-R/IV abuse and dependence criteria in a sample of 2405 adult twins who reported use of at least one illicit substance six or more times from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders (VATSPSUD). We estimated a symptom network for each substance class as well as a global network collapsed across all substance classes. We examined similarities and differences across the 6 networks in terms of symptom-to-symptom connections and symptom centrality. RESULTS: The global network model revealed several interesting symptom connections, such as a strong predictive relation between tolerance and more-than-planned substance use. The most central symptom was using a drug more than planned. In addition, several interesting differences across substances emerged, both in the strength of symptom connections as well as the centrality of symptoms to each network. CONCLUSIONS: When analyzed as networks, abuse and dependence symptoms do not function equivalently across illicit substance classes. These findings suggest the value of analyzing individual symptoms and their associations to gain new insight into the mechanisms of SUD. PMID- 26898183 TI - The formation and function of ER-endosome membrane contact sites. AB - Recent advances in membrane contact site (MCS) biology have revealed key roles for MCSs in inter-organellar exchange, the importance of which is becoming increasingly apparent. Roles for MCSs in many essential physiological processes including lipid transfer, calcium exchange, receptor tyrosine kinase signalling, lipid droplet formation, autophagosome formation, organelle dynamics and neurite outgrowth have been reported. The ER forms an extensive and dynamic network of MCSs with a diverse range of functionally distinct organelles. MCSs between the ER and endocytic pathway are particularly abundant, suggesting important physiological roles. Here, our current knowledge of the formation and function of ER contact sites with endocytic organelles from studies in mammalian systems is reviewed. Their relatively poorly defined molecular composition and recently identified functions are discussed. In addition, likely, but yet to be established, roles for these contacts in lipid transfer and calcium signalling are considered. This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon. PMID- 26898187 TI - Two-component signal transduction system SaeRS is involved in competence and penicillin susceptibility in Staphylococcus epidermidis. AB - Staphylococcus epidermidis, which is a causative pathogen of nosocomial infection, expresses its virulent traits such as biofilm and autolysis regulated by two-component signal transduction system SaeRS. In this study, the S. epidermidis SaeRS was identified to negatively regulate the expression of genes involved in competence (comF, murF), cytolysis (lrgA), and autolysis (lytS) by DNA microarray or real-time RT-PCR analysis. In addition, saeRS mutant showed increased competence and higher susceptibility to antibiotics such as penicillin and oxacillin than the wild-type strain. The study will be helpful for understanding the characterization of the SaeRS in S. epidermidis. PMID- 26898188 TI - TGF-alpha and IL-6 plasma levels selectively identify CML patients who fail to achieve an early molecular response or progress in the first year of therapy. AB - Early molecular response (EMR, BCR-ABL1 (IS)?10% at 3 months) is a strong predictor of outcome in imatinib-treated chronic phase chronic myeloid leukemia (CP-CML) patients, but for patients who transform early, 3 months may be too late for effective therapeutic intervention. Here, we employed multiplex cytokine profiling of plasma samples to test newly diagnosed CP-CML patients who subsequently received imatinib treatment. A wide range of pro-inflammatory and angiogenesis-promoting cytokines, chemokines and growth factors were elevated in the plasma of CML patients compared with that of healthy donors. Most of these normalized after tyrosine kinase inhibitor treatment while others remained high in remission samples. Importantly, we identified TGF-alpha and IL-6 as novel biomarkers with high diagnostic plasma levels strongly predictive of subsequent failure to achieve EMR and deep molecular response, as well as transformation to blast crisis and event-free survival. Interestingly, high TGF-alpha alone can also delineate a poor response group raising the possibility of a pathogenic role. This suggests that the incorporation of these simple measurements to the diagnostic work-up of CP-CML patients may enable therapy intensity to be individualized early according to the cytokine-risk profile of the patient. PMID- 26898192 TI - A reduced graphene oxide nanofiltration membrane intercalated by well-dispersed carbon nanotubes for drinking water purification. AB - In this study, we report a promising rGO-CNT hybrid nanofiltration (NF) membrane that was fabricated by loading reduced graphene oxide that was intercalated with carbon nanotubes (rGO-CNTs) onto an anodic aluminum oxide (AAO) microfiltration membrane via a facile vacuum-assisted filtration process. To create this NF membrane, the CNTs were first dispersed using block copolymers (BCPs); the effects of the types and contents of BCPs used on the dispersion of CNTs have been investigated. The as-prepared rGO-CNT hybrid NF membranes were then used for drinking water purification to retain the nanoparticles, dyes, proteins, organophosphates, sugars, and particularly humic acid. Experimentally, it is shown that the rGO-CNT hybrid NF membranes have high retention efficiency, good permeability and good anti-fouling properties. The retention was above 97.3% even for methyl orange (327 Da); for other objects, the retention was above 99%. The membrane's permeability was found to be as high as 20-30 L m(-2) h(-1) bar(-1). Based on these results, we can conclude that (i) the use of BCPs as a surfactant can enhance steric repulsion and thus disperse CNTs effectively; (ii) placing well-dispersed 1D CNTs within 2D graphene sheets allows an uniform network to form, which can provide many mass transfer channels through the continuous 3D nanostructure, resulting in the high permeability and separation performance of the rGO-CNT hybrid NF membranes. PMID- 26898189 TI - A phase 2 study of three low-dose intensity subcutaneous bortezomib regimens in elderly frail patients with untreated multiple myeloma. AB - This phase 2 trial evaluated three low-dose intensity subcutaneous bortezomib based treatments in patients ?75 years with newly diagnosed multiple myeloma (MM). Patients received subcutaneous bortezomib plus oral prednisone (VP, N=51) or VP plus cyclophosphamide (VCP, N=51) or VP plus melphalan (VMP, N=50), followed by bortezomib maintenance, and half of the patients were frail. Response rate was 64% with VP, 67% with VCP and 86% with VMP, and very good partial response rate or better was 26%, 28.5% and 49%, respectively. Median progression free survival was 14.0, 15.2 and 17.1 months, and 2-year OS was 60%, 70% and 76% in VP, VCP, VMP, respectively. At least one drug-related grade ?3 non-hematologic adverse event (AE) occurred in 22% of VP, 37% of VCP and 33% of VMP patients; the discontinuation rate for AEs was 12%, 14% and 20%, and the 6-month rate of toxicity-related deaths was 4%, 4% and 8%, respectively. The most common grade ?3 AEs included infections (8-20%), and constitutional (10-14%) and cardiovascular events (4-12%); peripheral neuropathy was limited (4-6%). Bortezomib maintenance was effective and feasible. VP, VCP and VMP regimens demonstrated no substantial difference. Yet, toxicity was higher with VMP, suggesting that a two-drug combination followed by maintenance should be preferred in frail patients. PMID- 26898190 TI - High-affinity FRbeta-specific CAR T cells eradicate AML and normal myeloid lineage without HSC toxicity. AB - Acute myeloid leukemia (AML) is an aggressive malignancy, and development of new treatments to prolong remissions is warranted. Chimeric antigen receptor (CAR) T cell therapies appear promising but on-target, off-tumor recognition of antigen in healthy tissues remains a concern. Here we isolated a high-affinity (HA) folate receptor beta (FRbeta)-specific single-chain variable fragment (2.48 nm KD) for optimization of FRbeta-redirected CAR T-cell therapy for AML. T cells stably expressing the HA-FRbeta CAR exhibited greatly enhanced antitumor activity against FRbeta(+) AML in vitro and in vivo compared with a low-affinity FRbeta CAR (54.3 nm KD). Using the HA-FRbeta immunoglobulin G, FRbeta expression was detectable in myeloid-lineage hematopoietic cells; however, expression in CD34(+) hematopoietic stem cells (HSCs) was nearly undetectable. Accordingly, HA-FRbeta CAR T cells lysed mature CD14(+) monocytes, while HSC colony formation was unaffected. Because of the potential for elimination of mature myeloid lineage, mRNA CAR electroporation for transient CAR expression was evaluated. mRNA electroporated HA-FRbeta CAR T cells retained effective antitumor activity in vitro and in vivo. Together, our results highlight the importance of antibody affinity in target protein detection and CAR development and suggest that transient delivery of potent HA-FRbeta CAR T cells is highly effective against AML and reduces the risk for long-term myeloid toxicity. PMID- 26898194 TI - Non-Hodgkin lymphoma in Southern Africa: review of 487 cases from The International Non-Hodgkin Lymphoma Classification Project. AB - Comparative data on the distribution of non-Hodgkin lymphoma (NHL) subtypes in Southern Africa (SAF) is scarce. In this study, five expert haematopathologists classified 487 consecutive cases of NHL from SAF using the World Health Organization classification, and compared the results to North America (NA) and Western Europe (WEU). Southern Africa had a significantly lower proportion of low grade (LG) B-NHL (34.3%) and a higher proportion of high-grade (HG) B-NHL (51.5%) compared to WEU (54.5% and 36.4%) and NA (56.1% and 34.3%). High-grade Burkitt like lymphoma was significantly more common in SAF (8.2%) than in WEU (2.4%) and NA (2.5%), most likely due to human immunodeficiency virus infection. When SAF patients were divided by race, whites had a significantly higher frequency of LG B-NHL (60.4%) and a lower frequency of HG B-NHL (32.7%) compared to blacks (22.5% and 62.6%), whereas the other races were intermediate. Whites and other races had a significantly higher frequency of follicular lymphoma and a lower frequency of Burkitt-like lymphoma compared to blacks. The median ages of whites with LG B NHL, HG B-NHL and T-NHL (64, 56 and 67 years) were significantly higher than those of blacks (55, 41 and 34 years). Epidemiological studies are needed to better understand these differences. PMID- 26898191 TI - Mouse mesenchymal stem cells inhibit high endothelial cell activation and lymphocyte homing to lymph nodes by releasing TIMP-1. AB - Mesenchymal stem cells (MSC) represent a promising therapeutic approach in many diseases in view of their potent immunomodulatory properties, which are only partially understood. Here, we show that the endothelium is a specific and key target of MSC during immunity and inflammation. In mice, MSC inhibit activation and proliferation of endothelial cells in remote inflamed lymph nodes (LNs), affect elongation and arborization of high endothelial venules (HEVs) and inhibit T-cell homing. The proteomic analysis of the MSC secretome identified the tissue inhibitor of metalloproteinase-1 (TIMP-1) as a potential effector molecule responsible for the anti-angiogenic properties of MSC. Both in vitro and in vivo, TIMP-1 activity is responsible for the anti-angiogenic effects of MSC, and increasing TIMP-1 concentrations delivered by an Adeno Associated Virus (AAV) vector recapitulates the effects of MSC transplantation on draining LNs. Thus, this study discovers a new and highly efficient general mechanism through which MSC tune down immunity and inflammation, identifies TIMP-1 as a novel biomarker of MSC-based therapy and opens the gate to new therapeutic approaches of inflammatory diseases. PMID- 26898197 TI - Diagnosis of Parkinson's disease: Imaging and genetics. PMID- 26898195 TI - New cellular markers at diagnosis are associated with isolated central nervous system relapse in paediatric B-cell precursor acute lymphoblastic leukaemia. AB - In childhood acute lymphoblastic leukaemia (ALL), central nervous system (CNS) involvement is rare at diagnosis (1-4%), but more frequent at relapse (~30%). Because of the significant late sequelae of CNS treatment, early identification of patients at risk of CNS relapse is crucial. Using microarray-analysis, we discovered multiple differentially expressed genes between B-cell precursor (BCP) ALL cells in bone marrow (BM) and BCP-ALL cells in cerebrospinal fluid (CSF) at the time of isolated CNS relapse. After confirmation by real-time quantitative polymerase chain reaction, selected genes (including SCD and SPP1) were validated at the protein level by flowcytometric analysis of BCP-ALL cells in CSF. Further flowcytometric validation showed that a subpopulation of BCP-ALL cells (>1%) with a 'CNS protein profile' (SCD positivity and increased SPP1 expression) was present in the BM at diagnosis in patients who later developed an isolated CNS relapse, whereas this subpopulation was <1% or absent in all other patients. These data indicate that the presence of a (small) subpopulation of BCP-ALL cells with a 'CNS protein profile' at diagnosis (particularly SCD-positivity) is associated with isolated CNS relapse. Such information can be used to design new diagnostic and treatment strategies that aim at prevention of CNS relapse with reduced toxicity. PMID- 26898196 TI - Frequency and prognostic value of resistance/intolerance to hydroxycarbamide in 890 patients with polycythaemia vera. AB - The clinical significance of resistance/intolerance to hydroxycarbamide (HC) was assessed in a series of 890 patients with polycythaemia vera (PV). Resistance/intolerance to HC was recorded in 137 patients (15.4%), consisting of: need for phlebotomies (3.3%), uncontrolled myeloproliferation (1.6%), failure to reduce massive splenomegaly (0.8%), development of cytopenia at the lowest dose of HC to achieve a response (1.7%) and extra-haematological toxicity (9%). With a median follow-up of 4.6 years, 99 patients died, resulting in a median survival of 19 years. Fulfilling any of the resistance/intolerance criteria had no impact on survival but when the different criteria were individually assessed, an increased risk of death was observed in patients developing cytopenia [Hazard ratio (HR): 3.5, 95% confidence interval (CI): 1.5-8.3, P = 0.003]. Resistance/intolerance had no impact in the rate of thrombosis or bleeding. Risk of myelofibrotic transformation was significantly higher in those patients developing cytopenia (HR: 5.1, 95% CI: 1.9-13.7, P = 0.001) and massive splenomegaly (HR: 9.1, 95% CI: 2.3-35.9, P = 0.002). Cytopenia at the lowest dose required to achieve a response was also an independent risk factor for transformation to acute leukaemia (HR: 20.3, 95% CI: 5.4-76.5, P < 0.001). In conclusion, the unified definition of resistance/intolerance to HC delineates a heterogeneous group of PV patients, with those developing cytopenia being associated with an adverse outcome. PMID- 26898198 TI - Zika virus infections in three travellers returning from South America and the Caribbean respectively, to Montpellier, France, December 2015 to January 2016. AB - We report three unrelated cases of Zika virus infection in patients returning from Martinique, Brazil and Colombia respectively, to Montpellier, France. They developed symptoms compatible with a mosquito-borne disease, and serological and molecular investigations indicated a recent Zika virus infection. Considering the recent warning for the likely teratogenicity of Zika virus and the presence of competent mosquito vectors in southern France, these cases highlight the need for awareness of physicians and laboratories in Europe. PMID- 26898199 TI - Validating the Children's Depression Inventory in the context of Rwanda. AB - BACKGROUND: Depression is often co-morbid with chronic conditions, and when combined with HIV it can increase progression and reduce survival. A brief and accurate screening tool for depression among children living with HIV is necessary to increase access to mental health care and improve HIV-related outcomes in the long-term. METHODS: A validation study was conducted, comparing the Children's Depression Inventory (CDI) with a structured clinical assessment as the gold standard among children living with HIV ages 7-14 years in Rwanda. The response rate was 87 % and the analysis was performed among 100 study participants. RESULTS: Twenty-five percent of children had a diagnosis of depression based on the clinical interview. Sensitivity of the CDI ranged from 44 to 76 % and specificity was 92 to 100 % for cut-off scores from 5 to 9. The area under the curve (AUC) for receiver operating characteristic analysis, an estimate of overall accuracy, was 0.87 (95 % confidence interval: 0.77 - 0.97). CONCLUSIONS: The significant prevalence of depression among children living with HIV in Rwanda reflects a critical need to advance mental health care in this population. Although overall accuracy of the CDI is reasonable in this context, further research needs to be done to develop a more sensitive measure of depression in this vulnerable population. Development of a highly sensitive screening measure will be a fundamental step towards improving access to mental health care among children living with HIV, potentially improving health outcomes and quality of life in the long-term as this vulnerable population transitions into adulthood. PMID- 26898201 TI - Improved sensitivity via layered-double-hydroxide-uniformity-dependent chemiluminescence. AB - In the last two decades nanoparticles have been widely applied to enhance chemiluminescence (CL). The morphology of nanoparticles has an important influence on nanoparticle-amplified CL. However, studies of nanoparticle amplified CL focus mainly on the size and shape effects, and no attempt has been made to explore the influence of uniformity in nanoparticle-amplified CL processes. In this study we have investigated nanoparticle uniformity in the luminol-H2O2 CL system using layered double hydroxides (LDHs) as a model material. The results demonstrated that the uniformity of LDHs played a key role in CL amplification. A possible mechanism is that LDHs with high uniformity possess abundant catalytic active sites, which results in high CL intensity. Meanwhile, the sensitivity for H2O2 detection was increased by one order of magnitude (1.0 nM). Moreover, the uniform-LDH-amplified luminol CL could be applied to selective detection of glucose in human plasma samples. Furthermore, such a uniformity-dependent CL enhancement effect could adapted to other redox CL systems-for example, the peroxynitrous acid (ONOOH) CL system. PMID- 26898202 TI - Emerging scanning probe approaches to the measurement of ionic reactivity at energy storage materials. AB - Many modern energy storage technologies operate via the nominally reversible shuttling of alkali ions between an anode and a cathode capable of hosting them. The degradation process that occurs with normal usage is not yet fully understood, but emerging progress in analytical tools may help address this knowledge gap. By interrogating ionic fluxes over electrified surfaces, scanning probe methods may identify features that impact the local cyclability of a material and subsequently help inform rational electrode design for future generations of batteries. Methods developed for identifying ion fluxes for batteries show great promise for broader applications, including biological interfaces, corrosion, and catalysis. PMID- 26898203 TI - Optimization and application of atmospheric pressure chemical and photoionization hydrogen-deuterium exchange mass spectrometry for speciation of oxygen-containing compounds. AB - This paper presents a detailed investigation of the feasibility of optimized positive and negative atmospheric pressure chemical ionization (APCI) mass spectrometry (MS) and atmospheric pressure photoionization (APPI) MS coupled to hydrogen-deuterium exchange (HDX) for structural assignment of diverse oxygen containing compounds. The important parameters for optimization of HDX MS were characterized. The optimized techniques employed in the positive and negative modes showed satisfactory HDX product ions for the model compounds when dichloromethane and toluene were employed as a co-solvent in APCI- and APPI-HDX, respectively. The evaluation of the mass spectra obtained from 38 oxygen containing compounds demonstrated that the extent of the HDX of the ions was structure-dependent. The combination of information provided by different ionization techniques could be used for better speciation of oxygen-containing compounds. For example, (+) APPI-HDX is sensitive to compounds with alcohol, ketone, or aldehyde substituents, while (-) APPI-HDX is sensitive to compounds with carboxylic functional groups. In addition, the compounds with alcohol can be distinguished from other compounds by the presence of exchanged peaks. The combined information was applied to study chemical compositions of degraded oils. The HDX pattern, double bond equivalent (DBE) distribution, and previously reported oxidation products were combined to predict structures of the compounds produced from oxidation of oil. Overall, this study shows that APCI- and APPI-HDX MS are useful experimental techniques that can be applied for the structural analysis of oxygen-containing compounds. PMID- 26898204 TI - Comparative studies of peak intensities and chromatographic separation of proteolytic digests, PTMs, and intact proteins obtained by nanoLC-ESI MS analysis at room and elevated temperatures. AB - This work demonstrates that the chromatographic separation performed at highly stabilized elevated temperature results in significant improvements in sensitivity, quantitative accuracy, chromatographic resolution, and run-to-run reproducibility of nanoLC-MS analysis of complex peptides mixtures. A newly developed platform was shown to provide conditions for accurate temperature stabilization and temperature homogeneity when performing nanoLC-ESI MS analysis. We quantitatively assessed and compared the recovery of peptides and small proteins from nanoLC columns at room and elevated temperatures. We found that analyses performed at highly stabilized elevated temperatures led to improved detection sensitivity, reproducibility, and chromatographic resolution in reversed-phase LC separation of unmodified peptides (both hydrophilic and hydrophobic), post-translationally modified peptides (O-phosphorylated), and small intact proteins. The analytical benefits of elevated temperatures for qualitative and quantitative proteomic LC-MS profiling were demonstrated using mixtures of synthetic peptides, tryptic digests of mixtures of model proteins, and digested total lysates of isolated rat kidney mitochondria. The effect of elevated temperature on the ion suppression was also demonstrated. Graphical Abstract A fragment of overlaid LC retention time-m/z planar views demonstrates the improved separation performance in the analysis of a complex peptide mixture at elevated temperature. Retention time-m/z 2D peptide features detected at 60 degrees C (magenta) were matched and aligned with features detected at room temperature (green). PMID- 26898205 TI - Determination of 3,4-methylenedioxypyrovalerone (MDPV) in oral and nasal fluids by ion mobility spectrometry. AB - A fast and sensitive methodology has been developed for the evaluation of the 3,4 methylenedioxypyrovalerone (MDPV) consumed. Based on ion mobility spectrometry (IMS), MDPV was directly determined in nasal fluids with a limit of detection (LOD) in the order of 22 ng mL(-1), which corresponds to an absolute amount of 33 ng of MDPV per swab. MDPV was also determined after liquid-liquid microextraction (LLME) in oral fluids to avoid matrix effects, obtaining a LOD value of 4.4 ng mL(-1) in oral fluid samples. The IMS spectrum for MDPV exhibited a peak with K0 = 1.210 +/- 0.005 cm(2)V(-1) s(-1) at a drift time of 14.62 ms, the total analysis time being 4.5 min per oral fluid and 1.5 min per nasal fluid sample. Samples must be analyzed within 24 h following collection and dissolution in 2 propanol, based on the complementary stability studies. PMID- 26898206 TI - Pesticide analysis at ppt concentration levels: coupling nano-liquid chromatography with dielectric barrier discharge ionization-mass spectrometry. AB - We report the coupling of nano-liquid chromatography (nano-LC) with an ambient dielectric barrier discharge ionization (DBDI)-based source. Detection and quantification were carried out by high-resolution mass spectrometry (MS), using an LTQ-Orbitrap in full scan mode. Despite the fact that nano-LC systems are rarely used in food analysis, this coupling was demonstrated to deliver extremely high sensitivity in pesticide analysis, with limits of detection (LODs) as low as 10 pg/mL. In all cases, the limits of quantification (LOQs) were compliant with the current EU regulation. An excellent signal linearity over up to four orders of magnitude was also observed. Therefore, this method can easily compete with conventional GC-(EI)-MS or LC-ESI-MS/MS methods and in some cases outperform them. The method was successfully tested for food sample analysis, with apples and baby food, extracted using the QuEChERS approach. Our results demonstrate an outstanding sensitivity (at femtogram level) and reproducibility of the nano-LC DBDI coupling, capable of improving routine pesticide analysis. To the best of our knowledge, this is the most sensitive and reproducible plasma-MS-based method for pesticide analysis reported to date. PMID- 26898208 TI - Response to the letter to the editor from Morfeld. PMID- 26898207 TI - Current opinion and consensus statement regarding the diagnosis, prognosis, and treatment of patients with essential thrombocythemia: a survey of the Spanish Group of Ph-negative Myeloproliferative Neoplasms (GEMFIN) using the Delphi method. AB - The current consensus on the diagnosis, prognosis, and treatment of essential thrombocythemia (ET) is based on experts' recommendations. However, several aspects of the diagnosis of, prognosis of, and therapy for ET are still controversial. The Delphi method was employed with an expert panel of members of the Spanish Group of Ph-negative Myeloproliferative Neoplasms in order to identify the degree of agreement on the diagnosis, prognosis, and treatment of ET. Nine leading experts selected a total of 41 clinical hematologists with well known expertise in ET. An electronic questionnaire was used to collect the questions rated in a four-step scale. The questions were grouped into four blocks: diagnosis, risk stratification, goals of therapy, and treatment strategy. After the first round consisting of 80 questions, a second round including 14 additional questions focused on the recommendations advocated by experts of the European LeukemiaNet in 2011 was analyzed. The median and mean values for the first and second rounds were calculated. A summary of the conclusions considered as the most representative of each block of questions is presented. The Delphi method is a powerful instrument to address the current approaches and controversies surrounding ET. PMID- 26898200 TI - Red meat, poultry, and fish intake and breast cancer risk among Hispanic and Non Hispanic white women: The Breast Cancer Health Disparities Study. AB - PURPOSE: There is suggestive but limited evidence for a relationship between meat intake and breast cancer (BC) risk. Few studies included Hispanic women. We investigated the association between meats and fish intake and BC risk among Hispanic and NHW women. METHODS: The study included NHW (1,982 cases and 2,218 controls) and the US Hispanics (1,777 cases and 2,218 controls) from two population-based case-control studies. Analyses considered menopausal status and percent Native American ancestry. We estimated pooled ORs combining harmonized data from both studies, and study- and race-/ethnicity-specific ORs that were combined using fixed or random effects models, depending on heterogeneity levels. RESULTS: When comparing highest versus lowest tertile of intake, among NHW we observed an association between tuna intake and BC risk (pooled OR 1.25; 95 % CI 1.05-1.50; trend p = 0.006). Among Hispanics, we observed an association between BC risk and processed meat intake (pooled OR 1.42; 95% CI 1.18-1.71; trend p < 0.001), and between white meat (OR 0.80; 95% CI 0.67-0.95; trend p = 0.01) and BC risk, driven by poultry. All these findings were supported by meta-analysis using fixed or random effect models and were restricted to estrogen receptor-positive tumors. Processed meats and poultry were not associated with BC risk among NHW women; red meat and fish were not associated with BC risk in either race/ethnic groups. CONCLUSIONS: Our results suggest the presence of ethnic differences in associations between meat and BC risk that may contribute to BC disparities. PMID- 26898209 TI - Mohner 2015: the suggested approach does not correct for competing causes reliably and overstates SMRs. PMID- 26898210 TI - Erratum to: Metabolomic profiling reveals novel biomarkers of alcohol intake and alcohol-induced liver injury in community-dwelling men. PMID- 26898211 TI - Intraoperative myelography of traumatic spine injury in patients with ankylosing spondylitis. Technical note. AB - BACKGROUND: Ankylosing spondylitis (AS) is an autoimmune inflammatory arthritis causing ossifications and rigidity of the spinal column. Patients with AS have a high incidence of spinal fractures, especially in the cervical spine, with a high rate of epidural hematomas. These have hazardous consequences, including neurological sequelae, and high morbidity and mortality. Diagnostics rely on CT and MRI scans, and therapy, usually open decompression and fixation, has to be done as soon as possible to enable recovery. However, in many cases, performing MRI scans is not possible for several reasons. METHODS: We present a case of an AS patient with paraparesis below T-8 after a fall who was not able to undergo MRI scan due to severe obesity, hyperkyphosis, and mechanical ventilation. CT scan did not demonstrate any fractures or hemorrhages in the thoracic spine and in addition a standard myelography could not be performed due to ossifications of ligaments. As an alternative, we performed an intra-operative myeolgraphy. Intra operative installation of a lumbar drain made a myelography and post-myelographic CT scan feasible. RESULTS: The scan revealed a contrast stop at T-10 and subsequently operative decompression and evacuation of the hematoma were performed. CONCLUSIONS: We present a quick and safe technique, performed in the operation room (OR), to detect intra-spinal lesions in patients with contraindications for MRI, or for cases where MRI scans cannot be performed. PMID- 26898213 TI - The impact of the Ponseti treatment method on parents and caregivers of children with clubfoot: a comparison of two urban populations in Europe and Africa. AB - PURPOSE: With the Ponseti treatment method established as the gold standard, children with clubfeet face a prolonged treatment regime that might impact on their families. We aimed to determine how Ponseti treatment influences the lives of parents and caregivers and what coping strategies they use. Secondarily, we aimed to identify any potential differences between two urban referral centres for clubfoot. METHODS: A total of 115 parents of children affected with idiopathic clubfoot were recruited and included in two groups: one from the United Kingdom (UK) and the other from South Africa (SA). The participants completed the following three instruments: the Impact on Family Scale (IOFS), the Multidimensional Scale of Perceived Social Support (MSPSS), and the Brief COPE. RESULTS: During the bracing phase, the IOFS showed a trend towards lower scores when compared to the casting phase for both cohorts (p = 0.247 and p = 0.434, respectively). The SA population scored higher than the UK in the MSPSS in both casting (p = 0.002) and bracing phases (p = 0.004) and used coping strategies at a significantly higher level when compared to the UK population (p < 0.05) in both treatment phases. CONCLUSION: This is the first study to show that Ponseti treatment for clubfoot causes an impact on family function. In SA, perceived social support is higher and coping strategies are used more often than in the UK to deal with the stressful circumstances of treatment. PMID- 26898214 TI - The BEM-FDM model of thermal processes proceeding in the domain of the human finger. AB - PURPOSE: The problem of the numerical modeling of thermal processes proceeding in the non-homogeneous domain of the human finger is discussed. The domain considered constitutes the assembling of soft and bone tissues and the system of supplying blood vessels (arteries and veins). The mathematical description of the process analyzed corresponds to the so-called vascular models. METHODS: At the stage of numerical modeling the algorithm being the composition of the boundary element method (BEM) and the finite difference method (FDM) is applied. RESULTS: The algorithm presented allows one to determine the steady state temperature field in the finger domain in natural convection conditions. To verify the effectiveness and exactness of the method of the problem solution, the thermal imaging measurements of the finger surface temperature have been done. CONCLUSIONS: The compatibility of numerical and experimental results (the natural convection conditions) has proved to be quite satisfactory. It is possible to use the algorithm proposed for the modeling of thermal processes proceeding in the conditions of low or high ambient temperatures and the big values of heat transfer coefficients. The impact of protective clothing on the temperature field in the domain of the finger can also be analyzed. PMID- 26898212 TI - Cardiac implantable electronic device lead-based masses and atrial fibrillation ablation: a case-based illustration of periprocedural anticoagulation management strategies. AB - INTRODUCTION: Cardiac implantable electronic device (CIED) leads frequently develop echogenic masses. However, the nature of these masses is not well understood. In patients in whom atrial fibrillation (AF) catheter ablation is planned, there is concern that transseptal puncture may result in cerebrovascular embolism of these masses. The optimal therapeutic strategy in this setting remains undefined. METHODS: We describe six patients identified over a 6-year period (2008-2014) with device lead-based masses prior to or at the time of AF ablation. We examined the anticoagulation strategy and periprocedural management based on mass identification. RESULTS: In all six patients (age 39-73; four males), the device lead mass was found in the right atrium. The average mass size was 11 +/- 1.3 mm. The majority of patients were already on anticoagulation (5/6; 83 %), and an intensified anticoagulation regimen was initiated (INR goal 3.0). In all six patients, the size of the device lead mass decreased on repeat imaging. In two sixths (33 %) patients, the lead-based mass completely resolved within 2 months. The remaining four patients had persistent lead-based masses (average follow-up of 10.9 +/- 9.6 months). DISCUSSION: We describe a series of patients with CIED lead-based masses found at the time of ablation. These cases illustrate that lead-based masses can disappear while patients are on high intensity anticoagulation, most compatible with a thrombotic origin. These early data will need to be assessed in larger cohorts for further validation and evaluation of safety. PMID- 26898216 TI - Self-Organization and Vesicle Formation of Amphiphilic Fulleromonodendrons Bearing Oligo(poly(ethylene oxide)) Chains. AB - A new series of N-methylfulleropyrrolidines bearing oligo(poly(ethylene oxide)) appended Percec monodendrons (fulleromonodendrons, 4a-f) have been synthesized. The substituted position of the oligo(poly(ethylene oxide)) chain(s) on the phenyl group of the Percec monodendron for 4a-f was varied, which is at the 4-, 2,4-, 3,5-, 3,4,5-, 2,3,4- and 2,4,6- position, respectively. 4a-e are obtained as solids at 25 degrees C and can self-organize into lamellar phases as revealed by X-ray diffraction (XRD) and small-angle X-ray scattering (SAXS) measurements, while 4f appears as a viscous liquid. The substitution patterns of the oligo(poly(ethylene oxide)) chain(s) also significantly influence the solubility of 4a-f, especially in ethanol and water. Formation of self-organized supramolecular structures of 4d and 4e in water as well as 4d in ethanol is evidenced from UV-vis and dynamic light scattering (DLS) measurements. Further studies in water using various imaging techniques including transmission electron microscopy (TEM), freeze-fracture TEM (FF-TEM), cryo-TEM and atomic force microscopy (AFM) observations revealed the formation of well-defined vesicles for 4d and plate-like aggregates for 4e, indicating that the aggregation behavior of the fulleromonodendrons is highly dependent on their molecular structures. For 4d in ethanol, only irregular aggregates were noticed, indicating the solvent also plays a role on regulating the aggregation behavior. After functionalization with the Percec monodendrons, 4a-f can preserve the intriguing electrochemical properties of pristine C60 as revealed by cyclic voltammetries. The thermotropic properties of 4a-f have also been investigated. It was found that all of them show good thermal stability, but no mesophases were detected within the investigated temperature ranges. PMID- 26898215 TI - A Polysaccharide from Ganoderma atrum Improves Liver Function in Type 2 Diabetic Rats via Antioxidant Action and Short-Chain Fatty Acids Excretion. AB - The present study was to evaluate the beneficial effect of polysaccharide isolated from Ganoderma atrum (PSG-1) on liver function in type 2 diabetic rats. Results showed that PSG-1 decreased the activities of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), while increasing hepatic glycogen levels. PSG-1 also exerted strong antioxidant activities, together with upregulated mRNA expression of peroxisome proliferator-activated receptor-gamma (PPAR-gamma), glucose transporter-4 (GLUT4), phosphoinositide 3 kinase (PI3K), and phosphorylated-Akt (p-Akt) in the liver of diabetic rats. Moreover, the concentrations of short-chain fatty acids (SCFA) were significantly higher in the liver, serum, and faeces of diabetic rats after treating with PSG-1 for 4 weeks. These results suggest that the improvement of PSG-1 on liver function in type 2 diabetic rats may be due to its antioxidant effects, SCFA excretion in the colon from PSG-1, and regulation of hepatic glucose uptake by inducing GLUT4 translocation through PI3K/Akt signaling pathways. PMID- 26898218 TI - Left bronchial compression and pulmonary hypertension related to anomalous right pulmonary artery. AB - Anomalous origin of a pulmonary artery from the ascending aorta is a congenital defect that can be complicated by pulmonary arterial hypertension, typically due to vascular disease if the anomaly is left uncorrected past 6 months of age. We describe a unique case of severe pulmonary arterial hypertension with this defect in a 1-month-old infant unexpectedly caused instead by bronchial compression from her dilated left pulmonary artery. PMID- 26898217 TI - Tubulin inhibitors in non-small cell lung cancer: looking back and forward. AB - INTRODUCTION: Although the advent of target therapy for lung cancer has brought about outstanding results, this benefit is confined to a subgroup of molecularly selected patients, whereas for most non-small cell lung cancer (NSCLC) patients, chemotherapy still represents the milestone of treatment. Since their introduction into clinics, microtubule targeting agents (MTA), including vinca alkaloids and taxanes, have been extensively used for NSCLC in different settings and combinations. AREAS COVERED: In this review, MTA are classified according to their mechanism of action, with a focus on the most common mechanisms of resistance. Moreover, an overview of the most remarkable clinical data regarding MTA in adjuvant, neoadjuvant and advanced setting is provided. Finally, the novel mitotic kinases inhibitors are described according to their different mechanism of action and clinical activity compared to MTA. EXPERT OPINION: Unfortunately, the awaited benefit deriving from the actually available chemotherapeutic regimens for advanced NSCLC has reached a plateau. In this scenario, the identification of reliable predictive biomarkers represents a major challenge. Moreover, different schedules for MTA administration are currently under investigation, such as the combination of MTA with other drugs able to bypass the resistance derived from the 'mitotic slippage' and the use of metronomic administration of spindle poisons with anti-angiogenic or immunomodulatory agents. PMID- 26898219 TI - In Vitro Comparison of Contemporary Radiographic Imaging Techniques for Measurement of Inter-radicular Width. PMID- 26898220 TI - Inhibition of carbonic anhydrase from Trypanosoma cruzi for the management of Chagas disease: an underexplored therapeutic opportunity. AB - An alpha-carbonic anhydrases (CAs, EC 4.2.1.1) was recently discovered, cloned and characterized in the genome of the protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease, a neglected but widespread tropical disease. Inhibition of this alpha-CAs (TcCA) with anions, sulfonamides, sulfamates, thiols and hydroxamates has been investigated in detail, with several low nanomolar in vitro inhibitors. Although the sulfonamides were the best in vitro inhibitors, they showed no ex vivo anti-T. cruzi activity, due to poor penetration. However, some thiols and hydroxamates acting as low nanomolar TcCA inhibitors also showed significant antitrypanosomal ex vivo activity, making this enzyme an attractive yet underexplored drug target for the management of Chagas disease. PMID- 26898222 TI - Multicomponent syntheses of functional chromophores. AB - Multicomponent reactions are a valuable tool for the synthesis of functional pi electron systems. Two different approaches can be taken into account for accessing the target structures. In the more conventional scaffold approach an already existing chromophore is coupled with other components to give a complex functional pi-system. Here, electronically monotonous components can also be introduced, which may exert synergistic electronic effects within the novel compound. The more demanding chromophore concept generates a complete pi-electron system and a scaffold concurrently. The latter approach is particularly stimulating for methodologists since pi-systems might be accessible from simple starting materials. This review encompasses the advances in the preparation of functional pi-electron systems via multicomponent processes during the past few years, based both on the scaffold and chromophore concepts. Besides the synthetic strategies the most important properties, i.e. redox potentials, absorption and emission maxima or fluorescence quantum yields, of the synthesized molecules are highlighted. PMID- 26898223 TI - Arabidopsis thaliana NIP7;1 is involved in tissue arsenic distribution and tolerance in response to arsenate. AB - The Arabidopsis aquaglyceroporin NIP7;1 is involved in uptake and tolerance to the trivalent arsenic species arsenite. Here, we show that NIP7;1 is also involved in the response to pentavalent arsenate. Loss of function of NIP7;1 improved tolerance to arsenate and reduced arsenic levels in both the phloem and xylem, resulting in altered arsenic distribution between tissues. There was no clear correlation between growth and shoot arsenic concentration. This is the first report detailing the involvement of a NIP transporter in response to arsenate. The data suggest that these proteins are relevant targets for breeding and engineering arsenic tolerance in crops. PMID- 26898221 TI - A Role for the Long Noncoding RNA SENCR in Commitment and Function of Endothelial Cells. AB - Despite the increasing importance of long noncoding RNA in physiology and disease, their role in endothelial biology remains poorly understood. Growing evidence has highlighted them to be essential regulators of human embryonic stem cell differentiation. SENCR, a vascular-enriched long noncoding RNA, overlaps the Friend Leukemia Integration virus 1 (FLI1) gene, a regulator of endothelial development. Therefore, we wanted to test the hypothesis that SENCR may contribute to mesodermal and endothelial commitment as well as in endothelial function. We thus developed new differentiation protocols allowing generation of endothelial cells from human embryonic stem cells using both directed and hemogenic routes. The expression of SENCR was markedly regulated during endothelial commitment using both protocols. SENCR did not control the pluripotency of pluripotent cells; however its overexpression significantly potentiated early mesodermal and endothelial commitment. In human umbilical endothelial cell (HUVEC), SENCR induced proliferation, migration, and angiogenesis. SENCR expression was altered in vascular tissue and cells derived from patients with critical limb ischemia and premature coronary artery disease compared to controls. Here, we showed that SENCR contributes to the regulation of endothelial differentiation from pluripotent cells and controls the angiogenic capacity of HUVEC. These data give novel insight into the regulatory processes involved in endothelial development and function. PMID- 26898224 TI - Vulnerable Populations in Hospital and Health Care Emergency Preparedness Planning: A Comprehensive Framework for Inclusion. AB - INTRODUCTION: As attention to emergency preparedness becomes a critical element of health care facility operations planning, efforts to recognize and integrate the needs of vulnerable populations in a comprehensive manner have lagged. This not only results in decreased levels of equitable service, but also affects the functioning of the health care system in disasters. While this report emphasizes the United States context, the concepts and approaches apply beyond this setting. OBJECTIVE: This report: (1) describes a conceptual framework that provides a model for the inclusion of vulnerable populations into integrated health care and public health preparedness; and (2) applies this model to a pilot study. METHODS: The framework is derived from literature, hospital regulatory policy, and health care standards, laying out the communication and relational interfaces that must occur at the systems, organizational, and community levels for a successful multi level health care systems response that is inclusive of diverse populations explicitly. The pilot study illustrates the application of key elements of the framework, using a four-pronged approach that incorporates both quantitative and qualitative methods for deriving information that can inform hospital and health facility preparedness planning. CONCLUSIONS: The conceptual framework and model, applied to a pilot project, guide expanded work that ultimately can result in methodologically robust approaches to comprehensively incorporating vulnerable populations into the fabric of hospital disaster preparedness at levels from local to national, thus supporting best practices for a community resilience approach to disaster preparedness. PMID- 26898225 TI - ROTEM monitoring of activated and non-activated prothrombin complex concentrate correction of dilutional coagulopathy. AB - OBJECTIVES: Prothrombin complex concentrates have been used to correct dilutional coagulopathy, but many preparations contain anticoagulants, such as heparin, to counteract their prothrombotic effects. These anticoagulants can interfere with haemostatic assays. The aim of this study was to monitor two different prothrombin complex concentrates for the treatment of albumin dilution in vitro, using rotational thromboelastometry with or without the heparin-antagonising agent protamine. METHODS: Citrated blood from 10 healthy volunteers was, in vitro, diluted 1:1 with 5% albumin and then corrected with a four-factor prothrombin complex concentrate with heparin anticoagulant (Confidex(r)) corresponding to a clinical dose of 43 IU/kg. Blood samples were tested with or without protamine. An activated prothrombin complex concentrate (APCC) (FEIBA(r)) without heparin in doses of 50 IU/kg and 100 IU/kg was also tested. Thromboelastometry was performed after recalcification. RESULTS: Albumin dilution significantly affected all thromboelastometry parameters. The four-factor PCC had an additional anticoagulant effect when added to the albumin-diluted blood; it was partially corrected by protamine for all parameters except maximum clot firmness. The APCC significantly improved all parameters, with over-correction of clotting time but only partial correction of maximum clot firmness. CONCLUSIONS: The anticoagulant content of many prothrombin complex concentrates needs to be considered when performing in vitro testing. A heparin-free APCC better corrected an in vitro albumin-induced dilutional coagulopathy than a four-factor PCC, despite of blocking heparin with protamine. PMID- 26898228 TI - [Subcutaneous ureteral bypass devices as a treatment option for bilateral ureteral obstruction in a cat with ureterolithiasis]. AB - A 6-year-old female spayed Domestic Shorthair cat was presented with acute lethargy, dehydration, marked azotemia, metabolic acidosis, left-sided renomegaly, and bilateral hydronephrosis. Ureterolithiasis and ureteral obstruction were suspected based on further diagnostics including abdominal sonography. Medical treatment was not successful. Fluoroscopically guided antegrade pyelography confirmed the diagnosis of bilateral ureteral obstruction due to ureterolithiasis. Subcutaneous ureteral bypass (SUB) devices were placed bilaterally, followed by close patient monitoring. Frequent reassessment of patient parameters and blood work served to adjust the fluid needs of the patient and to ensure proper hydration, correction of azotemia at an appropriate rate, and cardiovascular stability. After significant improvement of all patient parameters within 5 days, the patient was discharged from the hospital. Treatment included a dietary change to reduce the risk of stone formation as well as a phosphorus binder. Clinical and clinicopathologic parameters were unchanged at the 1- and 4- and 7-month rechecks (consistent with IRIS CKD stage II-NP-AP0), and both SUB devices continued to provide unobstructed urine flow. Bilateral placement of subcutaneous ureteral bypass devices may be a safe and potentially effective treatment option for acute bilateral ureteral obstruction in cats with ureterolithiasis. Strict patient monitoring and patient-centered postoperative treatment decisions are crucial to successful treatment outcomes. PMID- 26898227 TI - A large-scale perspective on stress-induced alterations in resting-state networks. AB - Stress is known to induce large-scale neural modulations. However, its neural effect once the stressor is removed and how it relates to subjective experience are not fully understood. Here we used a statistically sound data-driven approach to investigate alterations in large-scale resting-state functional connectivity (rsFC) induced by acute social stress. We compared rsfMRI profiles of 57 healthy male subjects before and after stress induction. Using a parcellation-based univariate statistical analysis, we identified a large-scale rsFC change, involving 490 parcel-pairs. Aiming to characterize this change, we employed statistical enrichment analysis, identifying anatomic structures that were significantly interconnected by these pairs. This analysis revealed strengthening of thalamo-cortical connectivity and weakening of cross-hemispheral parieto temporal connectivity. These alterations were further found to be associated with change in subjective stress reports. Integrating report-based information on stress sustainment 20 minutes post induction, revealed a single significant rsFC change between the right amygdala and the precuneus, which inversely correlated with the level of subjective recovery. Our study demonstrates the value of enrichment analysis for exploring large-scale network reorganization patterns, and provides new insight on stress-induced neural modulations and their relation to subjective experience. PMID- 26898226 TI - Complementary Post Transcriptional Regulatory Information is Detected by PUNCH-P and Ribosome Profiling. AB - Two novel approaches were recently suggested for genome-wide identification of protein aspects synthesized at a given time. Ribo-Seq is based on sequencing all the ribosome protected mRNA fragments in a cell, while PUNCH-P is based on mass spectrometric analysis of only newly synthesized proteins. Here we describe the first Ribo-Seq/PUNCH-P comparison via the analysis of mammalian cells during the cell-cycle for detecting relevant differentially expressed genes between G1 and M phase. Our analyses suggest that the two approaches significantly overlap with each other. However, we demonstrate that there are biologically meaningful proteins/genes that can be detected to be post-transcriptionally regulated during the mammalian cell cycle only by each of the approaches, or their consolidation. Such gene sets are enriched with proteins known to be related to intra-cellular signalling pathways such as central cell cycle processes, central gene expression regulation processes, processes related to chromosome segregation, DNA damage, and replication, that are post-transcriptionally regulated during the mammalian cell cycle. Moreover, we show that combining the approaches better predicts steady state changes in protein abundance. The results reported here support the conjecture that for gaining a full post-transcriptional regulation picture one should integrate the two approaches. PMID- 26898229 TI - Detection of HLA-C*04:212, a novel HLA-C*04 variant, in a Taiwanese hematopoietic stem cell donor. AB - Recombination and point mutation may result the formation of HLA-C*04:212. PMID- 26898230 TI - Break of symmetry in regenerating tobacco protoplasts is independent of nuclear positioning. AB - Nuclear migration and positioning are crucial for the morphogenesis of plant cells. We addressed the potential role of nuclear positioning for polarity induction using an experimental system based on regenerating protoplasts, where the induction of a cell axis de novo can be followed by quantification of specific regeneration stages. Using overexpression of fluorescently tagged extranuclear (perinuclear actin basket, kinesins with a calponin homology domain (KCH)) as well as intranuclear (histone H2B) factors of nuclear positioning and time-lapse series of the early stages of regeneration, we found that nuclear position is no prerequisite for polarity formation. However, polarity formation and nuclear migration were both modulated in the transgenic lines, indicating that both phenomena depend on factors affecting cytoskeletal tensegrity and chromatin structure. We integrated these findings into a model where retrograde signals are required for polarity induction. These signals travel via the cytoskeleton from the nucleus toward targets at the plasma membrane. PMID- 26898232 TI - Biomimetic water-collecting materials inspired by nature. AB - Nowadays, water shortage is a severe issue all over the world, especially in some arid and undeveloped areas. Interestingly, a variety of natural creatures can collect water from fog, which can provide a source of inspiration to develop novel and functional water-collecting materials. Recently, as an increasingly hot research topic, bioinspired materials with the water collection ability have captured vast scientific attention in both practical applications and fundamental research studies. In this review, we summarize the mechanisms of water collection in various natural creatures and present the fabrications, functions, applications, and new developments of bioinspired materials in recent years. The theoretical basis related to the phenomenon of water collection containing wetting behaviors and water droplet transportations is described in the beginning, i.e., the Young's equation, Wenzel model, Cassie model, surface energy gradient model and Laplace pressure equation. Then, the water collection mechanisms of three typical and widely researched natural animals and plants are discussed and their corresponding bioinspired materials are simultaneously detailed, which are cactus, spider, and desert beetles, respectively. This is followed by introducing another eight animals and plants (butterfly, shore birds, wheat awns, green bristlegrass, the Cotula fallax plant, Namib grass, green tree frogs and Australian desert lizards) that are rarely reported, exhibiting water collection properties or similar water droplet transportation. Finally, conclusions and outlook concerning the future development of bioinspired fog collecting materials are presented. PMID- 26898233 TI - Fano resonant Ge2Sb2Te5 nanoparticles realize switchable lateral optical force. AB - Sophisticated optical micromanipulation of small biomolecules usually relies on complex light, e.g., structured light, highly non-paraxial light, or chiral light. One emerging technique is to employ chiral light to drive the chiral nanoparticle along the direction perpendicular to the propagation of the light, i.e., the lateral optical force. Here, we theoretically study the lateral optical force exerted by a entirely Gaussian beam. For the very first time we demonstrate that the Fano resonances (FRs) of the Ge2Sb2Te5 (GST) phase-change nanoparticles encapsulated with Au shells could enable a conventional Gaussian laser to exert a lateral force on such a dielectric GST nanoparticle, attributed to the strongly asymmetric energy flow around the sphere in the dipole-quadrupole FRs. More interestingly, the direction of this lateral force could be reversible during the state transition (i.e., from amorphous to crystalline). By bonding small biomolecules to the outer surface of the phase-change nanoparticle, the particle behaves as a direction-selective vehicle to transport biomolecules along opposite directions, at pre-assessed states of the Ge2Sb2Te5 core correspondingly. Importantly, the origin of the reversal of the lateral optical force is further unveiled by the optical singularity of the Poynting vector. Our mechanism of tailoring the FRs of phase-change nanoparticles, not just limited to GST, may bring a new twist to optical micromanipulation and biomedical applications. PMID- 26898234 TI - Dictyophara europaea (Hemiptera: Fulgoromorpha: Dictyopharidae): description of immatures, biology and host plant associations. AB - The European lantern fly Dictyophara europaea (Linnaeus, 1767), is a polyphagous dictyopharid planthopper of Auchenorrhyncha commonly found throughout the Palaearctic. Despite abundant data on its distribution range and reports on its role in the epidemiology of plant-pathogenic phytoplasmas (Flavescence doree, FD C), literature regarding the biology and host plants of this species is scarce. Therefore, the aims of our study were to investigate the seasonal occurrence, host plant associations, oviposition behaviour and immature stages of this widespread planthopper of economic importance. We performed a 3-year field study to observe the spatio-temporal distribution and feeding sources of D. europaea. The insects's reproductive strategy, nymphal molting and behaviour were observed under semi-field cage conditions. Measurement of the nymphal vertex length was used to determine the number of instars, and the combination of these data with body length, number of pronotal rows of sensory pits and body colour pattern enabled the discrimination of each instar. We provide data showing that D. europaea has five instars with one generation per year and that it overwinters in the egg stage. Furthermore, our study confirmed highly polyphagous feeding nature of D. europaea, for all instars and adults, as well as adult horizontal movement during the vegetation growing season to the temporarily preferred feeding plants where they aggregate during dry season. We found D. europaea adult aggregation in late summer on Clematis vitalba L. (Ranunculaceae), a reservoir plant of FD-C phytoplasma strain; however, this appears to be a consequence of forced migration due to drying of herbaceous vegetation rather than to a high preference of C. vitalba as a feeding plant. Detailed oviposition behaviour and a summary of the key discriminatory characteristics of the five instars are provided. Emphasis is placed on the economic importance of D. europaea because of its involvement in epidemiological cycles of phytoplasma-induced plant diseases. PMID- 26898231 TI - CD36 is a co-receptor for hepatitis C virus E1 protein attachment. AB - The cluster of differentiation 36 (CD36) is a membrane protein related to lipid metabolism. We show that HCV infection in vitro increased CD36 expression in either surface or soluble form. HCV attachment was facilitated through a direct interaction between CD36 and HCV E1 protein, causing enhanced entry and replication. The HCV co-receptor effect of CD36 was independent of that of SR-BI. CD36 monoclonal antibodies neutralized the effect of CD36 and reduced HCV replication. CD36 inhibitor sulfo-N-succinimidyl oleate (SSO), which directly bound CD36 but not SR-BI, significantly interrupted HCV entry, and therefore inhibited HCV replication. SSO's antiviral effect was seen only in HCV but not in other viruses. SSO in combination with known anti-HCV drugs showed additional inhibition against HCV. SSO was considerably safe in mice. Conclusively, CD36 interacts with HCV E1 and might be a co-receptor specific for HCV entry; thus, CD36 could be a potential drug target against HCV. PMID- 26898236 TI - Evaluation of interobserver variability and diagnostic performance of developed MRI-based radiological scoring system for invasive placenta previa. AB - PURPOSE: To evaluate the interobserver variability and diagnostic performance of a developed magnetic resonance imaging (MRI)-based scoring system for invasive placenta previa. MATERIALS AND METHODS: Prenatal MR images of 70 women were retrospectively evaluated, 18 of whom were diagnosed with invasive placenta. The six MR features (dark band on T2 -weighted images, intraplacental abnormal vascularity, placental bulge, heterogeneous placenta, myometrial thinning, and placental protrusion sign) were scored on 5-point Likert scale separately, and the cumulative radiological score (CRS) was defined as the sum of each score. Two more experienced radiologists (readers A and B) and two less experienced residents (readers C and D) calculated the CRS. Interobserver variability was assessed by measuring the intraclass correlation coefficient. Diagnostic performance was evaluated by means of receiver operating characteristic (ROC) analysis. RESULTS: Interobserver variability for CRS was excellent for the more experienced radiologists (0.85), and good for all readers (0.72) and the less experienced residents (0.66). The area under the ROC curve (Az) and accuracy (Acc) for CRS were significantly higher or equivalent to those of other MR features for all readers (Az and Acc for reader A; CRS, 0.92, 91.4%; intraplacental T2 dark band, 0.83, P = 0.009, 81.4%, P = 0.03; intraplacental abnormal vascularity, 0.9, P = 0.3, 90.0%, P = 1.00; placental bulge, 0.81, P = 0.0008, 80.0%, P = 0.02; heterogeneous placenta, 0.85, P = 0.11, 74.3%, P = 0.002; myometrial thinning, 0.84, P = 0.06, 60.0%, P < 0.0001; placental protrusion sign, 0.81, P = 0.01, 81.4%, P = 0.26). CONCLUSION: This developed MRI based scoring system demonstrated excellent or good interobserver variability, and good diagnostic performance for invasive placenta previa. J. Magn. Reson. Imaging 2016;44:573-583. PMID- 26898235 TI - Placental Transfer of Perfluoroalkyl Substances and Associations with Thyroid Hormones: Beijing Prenatal Exposure Study. AB - Perfluoroalkyl substances (PFASs) have been detected in wildlife and human samples worldwide. Toxicology research showed that PFASs could interfere with thyroid hormone homeostasis. In this study, eight PFASs, fifteen PFAS precursors and five thyroid hormones were analyzed in 157 paired maternal and cord serum samples collected in Beijing around delivery. Seven PFASs and two precursors were detected in both maternal and cord sera with significant maternal-fetal correlations (r = 0.336 to 0.806, all P < 0.001). The median ratios of major PFASs concentrations in fetal versus maternal serum were from 0.25:1 (perfluorodecanoic acid, PFDA) to 0.65:1 (perfluorooctanoic acid, PFOA). Spearman partial correlation test showed that maternal thyroid stimulating hormone (TSH) was negatively correlated with most maternal PFASs (r = -0.261 to -0.170, all P < 0.05). Maternal triiodothyronin (T3) and free T3 (FT3) showed negative correlations with most fetal PFASs (r = -0.229 to -0.165 for T3; r = -0.293 to 0.169 for FT3, all P < 0.05). Our results suggest prenatal exposure of fetus to PFASs and potential associations between PFASs and thyroid hormone homeostasis in humans. PMID- 26898238 TI - Plasma functionalization for cyclic transition between neutral and charged excitons in monolayer MoS2. AB - Monolayer MoS2 (1L-MoS2) has photoluminescence (PL) properties that can greatly vary via transition between neutral and charged exciton PLs depending on carrier density. Here, for the first time, we present a chemical doping method for reversible transition between neutral and charged excitons of 1L-MoS2 using chlorine-hydrogen-based plasma functionalization. The PL of 1L-MoS2 is drastically increased by p-type chlorine plasma doping in which its intensity is easily tuned by controlling the plasma treatment duration. We find that despite their strong adhesion, a post hydrogen plasma treatment can very effectively dedope chlorine adatoms in a controllable way while maintaining robust structural integrity, which enables well-defined reversible PL control of 1L-MoS2. After exhaustive chlorine dedoping, the hydrogen plasma process induces n-type doping of 1L-MoS2, degrading the PL further, which can also be recovered by subsequent chlorine plasma treatment, extending the range of tunable PL into a bidirectional regime. This cyclically-tunable carrier doping method can be usefully employed in fabricating highly-tunable n- and p-type domains in monolayer transition-metal dichalcogenides suitable for two-dimensional electro-optic modulators, on-chip lasers, and spin- and valley-polarized light-emitting diodes. PMID- 26898237 TI - Effect of diabetic duration on hemorheological properties and platelet aggregation in streptozotocin-induced diabetic rats. AB - Diabetes mellitus with abnormal glucose concentration is associated with changes in hemorheological properties, endothelial function, and platelets hyperactivity. Disturbances may significantly be responsible for diabetes-related vascular complications. In this study, hemorheological and hemodynamic properties were measured according to diabetic duration after streptozotocin treatment in rats. For ex vivo measurements, an extracorporeal model was adopted. Flow rate and blood viscosity were measured using a microfluidic device. Erythrocyte aggregation and morphological parameters of erythrocytes were measured by modified erythrocyte sedimentation rate and the phase-contrast holography under in vitro conditions. The platelet aggregation and mean pressure in the femoral artery were estimated under ex vivo conditions. Hemorheological properties including blood viscosity, erythrocyte aggregation and shape parameters for the control group are significantly different with those for diabetic groups. The changes with respect to diabetic duration were relatively unnoticeable. However, the platelet aggregation is strongly dependent on the diabetic duration. Based on these results, hyperglycemia exposure may induce hemorheological variations in early stages of diabetes mellitus. High platelet aggregation may become more pronounced according to the diabetic duration caused by variations in hemorheological properties resulting in endothelial dysfunction. This study would be helpful in understanding the effects of diabetic duration on biophysical properties. PMID- 26898239 TI - Phytotherapeutic interventions in the management of biochemically recurrent prostate cancer: a systematic review of randomised trials. AB - OBJECTIVE: To evaluate the evidence from randomised trials for the efficacy and safety of phytotherapeutic interventions in the management of biochemically recurrent (BCR) prostate cancer, indicated by prostate-specific antigen (PSA) progression, numbers progressing to/time to initiation of androgen-deprivation therapy or salvage therapy. PATIENTS AND METHODS: MEDLINE (Ovid), EMBASE (Ovid), AMED (Ovid), CINAHL (EBSCO) and the Cochrane Library databases were searched. Clinical trials investigating phytotherapeutic interventions as dietary supplements or dietary components, including multi-component herbal formulations, in men with BCR prostate cancer were located. Eight of nine authors contacted for further information responded. Methodological quality was assessed using the Cochrane Collaboration's risk of bias assessment tool. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement for reporting systematic reviews was followed. RESULTS: Of 23 full-text articles assessed for eligibility, five met the criteria for inclusion. Two studies were placebo controlled; two were active control trials; and one a high-/low-dose trial. The interventions were administered as isolated phytochemicals (sulphoraphane), phytotherapeutic extracts [Pomi-T (pomegranate, turmeric, green tea and broccoli sprout extract), soy, lycopene, and POMx (pomegranate extract)], or plant-derived dietary items (soy and lycopene). All studies found serum PSA levels to stabilise, decrease or rise more slowly in a significant number of men, and three studies reported stabilising or lengthening of PSA-doubling time. Studies were generally of good quality, but sample sizes were predominantly small, and durations short. CONCLUSIONS: High-quality studies in this area are lacking. Sulphoraphane, lycopene, soy isoflavones, POMx, and Pomi-T are safe and well tolerated. There is limited evidence that they can affect PSA dynamics. No recommendation can be made for the use of these agents in managing prostate cancer morbidity and mortality until high-quality, fully powered studies are available. Recommendations are made for improving reproducibility and translation of findings with regard to study population, study endpoints, design, and the reporting of phytotherapeutic interventions. PMID- 26898240 TI - Early influenza vaccine effectiveness results 2015-16: I-MOVE multicentre case control study. PMID- 26898242 TI - On the outside looking in: redefining the role of analytical chemistry in the biosciences. AB - Biomedical research has moved on from the study of the structure of organs, cells and organelles. Today, the key questions that must be addressed to understand the body in health and disease are related to fundamental biochemistry: the distribution and speciation of chemicals, the regulation of chemical reactions, and the control of chemical environments. To see advances in this field, it is essential for analytical chemists to actively engage in this process, from beginning to end. In this Feature Article, we review the progress that has been made towards gaining an understanding of the chemistry of the body, while commenting on the intrinsic disconnect between new innovations in the field of analytical chemistry and practical application within the biosciences. We identify the challenges that prevent chemists from making a greater impact in this field, and highlight key steps for moving forward. PMID- 26898241 TI - Phthalimide-Derived N-Benzylpyridinium Halides Targeting Cholinesterases: Synthesis and Bioactivity of New Potential Anti-Alzheimer's Disease Agents. AB - In order to develop potent dual-binding cholinesterase inhibitors as potential drugs for the treatment of Alzheimer's disease, we designed and synthesized phthalimide-based acetylcholinesterase (AChE) inhibitors (7) containing a substituted N-benzylpyridinium residue. The in vitro anti-cholinesterase assay employing the target compounds against AChE and butyrylcholinesterase (BChE) revealed the 2-fluorobenzylpyridinium derivative 7d as the most potent compound against both enzymes, with IC50 values of 0.77 and 8.71 MUM. The docking study of compound 7d into the active site of AChE showed the gorge-spanning binding mode, in which the compound spans the narrow hydrophobic gorge from the bottom to the rim. PMID- 26898243 TI - Shp-2 knockdown prevents l-dopa-induced dyskinesia in a rat model of Parkinson's disease. AB - BACKGROUND: Dyskinesia, the major side effect of l-dopa therapy in PD, is mainly associated with nonphysiological stimulation of denervated receptors in the striatum. In particular, DA D1 receptor-mediated aberrant extracellular signal regulated protein kinases 1 and 2 activation have been associated with striatal changes leading to dyskinesia. We recently identified the tyrosine phosphatase Shp-2 as a crucial effector transmitting D1 receptor signaling to extracellular signal-regulated protein kinases 1 and 2 activation and reported the involvement of the D1 receptor/Shp-2/extracellular signal-regulated protein kinases 1 and 2 pathway in the development of l-dopa-induced dyskinesia. OBJECTIVES: In this study, the role of Shp-2 in l-dopa-induced dyskinesia development was investigated by in vivo silencing of Shp-2 in the striatum of the 6-hydroxy dopamine rat model of PD. METHODS: Lentiviral particles delivering short hairpin RNA were used to obtain long-term striatal Shp-2 downregulation. Rats were then treated with l-dopa and analyzed for both the improvement of akinesia and the development of l-dopa-induced dyskinesia. RESULTS: The results show that Shp-2 knockdown remarkably decreased extracellular signal-regulated protein kinases 1 and 2 phosphorylation and attenuated the severity of l-dopa-induced dyskinesia likely without compromising the therapeutic efficacy of l-dopa. CONCLUSION: These data suggest that the striatal D1 receptor/Shp-2 complex may represent a promising novel target for the development of antidyskinetic drugs. PMID- 26898244 TI - Neverland regulates embryonic moltings through the regulation of ecdysteroid synthesis in the water flea Daphnia magna, and may thus act as a target for chemical disruption of molting. AB - Embryo development in arthropods is accompanied by a series of moltings. A cladoceran crustacean Daphnia magna molts three times before reaching first instar neonate during embryogenesis. Previous studies argued ecdysteroids might regulate D. magna embryogenesis. However, no direct evidence between innate ecdysteroids fluctuation and functions has been forthcoming. Recently, we identified genes involved in ecdysteroid synthesis called, neverland (neverland1 and neverland 2) and shade and in the ecdysteroid degradation (Cyp18a1). To understand the physiological roles of ecdysteroids in D. magna embryos, we performed expression and functional analyzes of those genes. Examining innate ecdysteroids titer during embryogenesis showed two surges of ecdysteroids titer at 41 and 61 h after oviposition. The first and second embryonic moltings occurred at each ecdysteroid surge. Expression of neverland1 and shade began to increase before the first peak in ecdysteroid. Knockdown of neverland1 or shade by RNAi technique caused defects in embryonic moltings and subsequent development. The ecdysteroids titer seemingly decreased in nvd1-knowckdown embryos. Knockdown of Cyp18a1 resulted in early embryonic lethality before the first molting. Our in situ hybridization analysis revealed that nvd1 was prominently expressed in embryonic gut epithelium suggesting the site for an initial step of ecdysteroidgenesis, a conversion of cholesterol to 7 dehydrocholesterol and possibly for ecdysone production. Taken together, de novo ecdysteroid synthesis by nvd1 in the gut epithelial cells stimulates molting, which is indispensable for D. magna embryo development. These findings identify neverland as a possible target for chemicals, including various pesticides that are known to disrupt molting, development and reproduction. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26898245 TI - Effects of different supplemental soya bean oil levels on the performance of prepubertal Saanen goats: Oestrogen and progesterone release. AB - The aim of this study was to investigate the effects of different levels of soya bean oil in the total diet on the growth rate, metabolic changes, and oestrogen and progesterone release in Saanen goats. After dietary adaptation, 21 prepubertal goats (weight of 29.12 +/- 0.91 kg, 230 days old) were randomly distributed among three diets of D2: inclusion of 2% soya bean oil in the total diet; D3: basal diet - inclusion of 3% soya bean oil in the total diet; and D4: inclusion of 4% soya bean oil in the total diet. The basal diet (D3) was formulated to promote a daily gain of 0.140 kg. The goats were weighed, and their blood samples were collected weekly. Glucose, cholesterol, triglycerides, total protein, urea, non-esterified fatty acids, beta-hydroxybutyrate, oestrogen and progesterone in the plasma were measured. Prepubertal goats that were fed D4 exhibited a significantly lower dry matter intake, urea and cholesterol levels compared with the goats that were fed D2 and D3. Indeed, goats that were fed D4 displayed a significantly lower final weight than goats that were fed D2 and D3. In contrast, the inclusion of soya bean oil in the diet increased the progesterone and oestrogen concentrations, and goats that were fed D4 released a significantly higher concentration of progesterone than those that were fed D2 and D3. Furthermore, the percentage of goats with a progesterone level greater than 1 ng/ml (functional Corpus luteum) was significantly higher among the goats that were fed D3 and D4 than among those that were fed D2. In this study, although the inclusion of 4% soya bean oil in the diet decreased dry matter intake and growth rate, it increased progesterone concentration and the percentage of goats with a functional Corpus luteum, suggesting that the inclusion of soya bean oil accelerated puberty in prepubertal goats. PMID- 26898248 TI - Calcium Carbide: A Unique Reagent for Organic Synthesis and Nanotechnology. AB - Acetylene, HC=CH, is one of the primary building blocks in synthetic organic and industrial chemistry. Several highly valuable processes have been developed based on this simplest alkyne and the development of acetylene chemistry has had a paramount impact on chemical science over the last few decades. However, in spite of numerous useful possible reactions, the application of gaseous acetylene in everyday research practice is rather limited. Moreover, the practical implementation of high-pressure acetylene chemistry can be very challenging, owing to the risk of explosion and the requirement for complex equipment; special safety precautions need to be taken to store and handle acetylene under high pressure, which limit its routine use in a standard laboratory setup. Amazingly, recent studies have revealed that calcium carbide, CaC2 , can be used as an easy to-handle and efficient source of acetylene for in situ chemical transformations. Thus, calcium carbide is a stable and inexpensive acetylene precursor that is available on the ton scale and it can be handled with standard laboratory equipment. The application of calcium carbide in organic synthesis will bring a new dimension to the powerful acetylene chemistry. PMID- 26898247 TI - Lab-on-a-Drone: Toward Pinpoint Deployment of Smartphone-Enabled Nucleic Acid Based Diagnostics for Mobile Health Care. AB - We introduce a portable biochemical analysis platform for rapid field deployment of nucleic acid-based diagnostics using consumer-class quadcopter drones. This approach exploits the ability to isothermally perform the polymerase chain reaction (PCR) with a single heater, enabling the system to be operated using standard 5 V USB sources that power mobile devices (via battery, solar, or hand crank action). Time-resolved fluorescence detection and quantification is achieved using a smartphone camera and integrated image analysis app. Standard sample preparation is enabled by leveraging the drone's motors as centrifuges via 3D printed snap-on attachments. These advancements make it possible to build a complete DNA/RNA analysis system at a cost of ~$50 ($US). Our instrument is rugged and versatile, enabling pinpoint deployment of sophisticated diagnostics to distributed field sites. This capability is demonstrated by successful in flight replication of Staphylococcus aureus and lambda-phage DNA targets in under 20 min. The ability to perform rapid in-flight assays with smartphone connectivity eliminates delays between sample collection and analysis so that test results can be delivered in minutes, suggesting new possibilities for drone based systems to function in broader and more sophisticated roles beyond cargo transport and imaging. PMID- 26898249 TI - Primary hybrid THA using a polymethyl methacrylate-precoated stem: A single center experience with a 10-year minimum follow-up. AB - The high failure rate of cemented femoral components in the 1970s facilitated the improvement of the cementing technique and surface finishes such as polymethylmethacrylate (PMMA)-precoated stems, reporting a survival rate of >95% at 10 years from some studies. However, controversy persists regarding whether precoated femoral stems are associated with a longer revision-free prosthesis survival. The purpose of this study was to evaluate the clinical and radiological outcomes of PMMA-precoated femoral stems, and analyze factors associated with implant survival. We retrospectively reviewed 73 primary hybrid total hip arthroplasties performed using PMMA-precoated femoral stems. The mean age of the patients was 61 years. During the mean follow-up period of 13 years, 18 hips (24.7%) underwent aseptic loosening, and all of the loosened stems were subjected to revision surgery 8.8 years (range 4.6-15.5 years) from the index surgery. Younger age and poor cementing were significantly associated with aseptic loosening (P = 0.013 and P < 0.001, respectively). However, the aseptic loosening rate was also high at 13.1% even with a good cementing technique. In conclusion, the PMMA-precoated stem failed to show expected advantages and needs to be replaced with other surface finish stem designs. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1300-1306, 2017. PMID- 26898250 TI - What do biomarkers mark? PMID- 26898246 TI - A microRNA-mediated decrease in eukaryotic initiation factor 2alpha promotes cell survival during PS-341 treatment. AB - MicroRNAs (miRs) play pivotal roles in carcinogenesis and endoplasmic reticulum (ER) that performs the folding, modification and trafficking of proteins targeted to the secretory pathway. Cancer cells often endure ER stress during tumor progression but use the adaptive ER stress response to gain survival advantage. Here we report: (i) A group of miRs, including miR-30b-5p and miR-30c-5p, are upregulated by proteasome inhibitor PS-341 treatment, in HepG2 and MDA-MB-453 cells. (ii) Two representative PS-341-induced miRs: miR-30b-5p and miR-30c-5p are found to promote cell proliferation and anti-apoptosis in both tumor cells. (iii) eIF2alpha is confirmed as the congenerous target of miR-30b-5p and miR-30c-5p, essential to the anti-apoptotic function of these miRs. (iv) Upregulation of miR 30b-5p or miR-30c-5p, which occurs latter than the increase of phosphorylated eIF2alpha (p-eIF2alpha) in the cell under ER stress, suppresses the p eIF2alpha/ATF4/CHOP pro-apoptotic pathway. (v) Inhibition of the miR-30b-5p or miR-30c-5p sensitizes the cancer cells to the cytotoxicity of proteasome inhibition. In conclusion, we unravels a new miRs-based mechanism that helps maintain intracellular proteostasis and promote cell survival during ER stress through upregulation of miR-30b-5p and miR-30c-5p which target eIF2alpha and thereby inhibit the p-eIF2alpha/ATF4/CHOP pro-apoptotic pathway, identifying miR 30b-5p and miR-30c-5p as potentially new targets for anti-cancer therapies. PMID- 26898251 TI - Effectiveness of a standard secondary coronary prevention program: not obligate. PMID- 26898252 TI - Recurrent spontaneous dissection affecting different coronary arteries of a young female. PMID- 26898253 TI - Combined implantation of dual-chamber ICD and optimizer through a persistent left superior vena cava. PMID- 26898254 TI - What is your diagnosis? PMID- 26898255 TI - Left ventricular hypertrophy, inflammation, and insulin resistance. PMID- 26898256 TI - Author's Reply. PMID- 26898257 TI - Non-thyroidal illness syndrome and erectile function in males undergoing coronary artery bypass graft. PMID- 26898258 TI - Author's Reply. PMID- 26898259 TI - Medicine in philately: Rene T. H. Laennec, the father of stethoscope. PMID- 26898260 TI - Impressions from the PCR Istanbul Peripheral. PMID- 26898261 TI - Compression of left ventricle by a rare giant unruptured sinus of Valsalva aneurysm. PMID- 26898262 TI - A hypothermic case with giant Osborn waves and atrial fibrillation after using synthetic cannabinoid. PMID- 26898263 TI - Aortic valve aneurysm involved in interventricular septum. PMID- 26898264 TI - The influence of low-frequency variable magnetic fields in reducing pain experience after dental implant treatment. AB - The paper presents the evaluation of analgesic effect or magnetostimulation and magnetoledtherapy after implantation treatment. The study was conducted on 3 groups (Z applicator, IR applicator and conventional drug therapy) of 10 patients each of whom underwent a single implantation. Magnetostimulation was carried out using Viofor JPS Delux equipment. The patients were exposed to magnetic field for approx. 15 minutes before the treatment and during the visit after 6 hours after the implantation procedure. Pain perception of patients was recorded on the Visual Analogue Scale (VAS). RESULTS: the most intense pain was reported in the control group. The least intense pain appeared in the group with Z applicator. Patients using Z and IR applicators took analgesics less frequently and used much weaker analgesics than the control group. Pain perceived in the first group was between 0 and 2, while in the second group - between 2 and 3, and in the control group - between 3 and 5 in VAS scale. Magnetostimulation reduces patient's demand for analgesics after implantation procedures and yielded better effects in reduction of pain in comparison with magnetostimulation with LED therapy. PMID- 26898265 TI - Tailoring Biointerfaces for Electrocatalysis. AB - Bioelectrocatalysis is an expanding research area due to the use of this type of electrocatalysis in electrochemical biosensors, biofuel cells, bioelectrochemical cells, and biosolar cells. This feature article discusses recent advancements in tailoring the biointerface between electrodes and biocatalysts for facile electrocatalysis. This includes the design of pyrene moieties for directing the orientation of biocatalysts on electrode surfaces and mediation as well as the rational design of redox polymers for self-exchange-based electron transport to/from biocatalysts and the electrode and the use of bioscaffolding techniques for designing the bioelectrode structure. However, recent advances in the past decade have shown the importance of hybrid bioelectrocatalytic systems, and future work will be needed to use these same pyrene, redox polymer, and bioscaffolding techniques for hybrid bioelectrocatalysis. PMID- 26898267 TI - Public Domain HTS Fingerprints: Design and Evaluation of Compound Bioactivity Profiles from PubChem's Bioassay Repository. AB - Molecular profiling efforts aim at characterizing the biological actions of small molecules by screening them in hundreds of different biochemical and/or cell based assays. Together, these assays yield a rich data landscape of target-based and phenotypic effects of the tested compounds. However, submitting an entire compound library to a molecular profiling panel can easily become cost prohibitive. Here, we make use of historical screening assays to create comprehensive bioactivity profiles for more than 300 000 small molecules. These bioactivity profiles, termed PubChem high-throughput screening fingerprints (PubChem HTSFPs), report small molecule activities in 243 different PubChem bioassays. Although the assays originate from originally independently pursued drug or probe discovery projects, we demonstrate their value as molecular signatures when used in combination. We use these PubChem HTSFPs as molecular descriptors in hit expansion experiments for 33 different targets and phenotypes, showing that, on average, they lead to 27 times as many hits in a set of 1000 chosen molecules as a random screening subset of the same size (average ROC score: 0.82). Moreover, we demonstrate that PubChem HTSFPs retrieve hits that are structurally diverse and distinct from active compounds retrieved by chemical similarity-based hit expansion methods. PubChem HTSFPs are made freely available for the chemical biology research community. PMID- 26898266 TI - Multi-loci diagnosis of acute lymphoblastic leukaemia with high-throughput sequencing and bioinformatics analysis. AB - High-throughput sequencing (HTS) is considered a technical revolution that has improved our knowledge of lymphoid and autoimmune diseases, changing our approach to leukaemia both at diagnosis and during follow-up. As part of an immunoglobulin/T cell receptor-based minimal residual disease (MRD) assessment of acute lymphoblastic leukaemia patients, we assessed the performance and feasibility of the replacement of the first steps of the approach based on DNA isolation and Sanger sequencing, using a HTS protocol combined with bioinformatics analysis and visualization using the Vidjil software. We prospectively analysed the diagnostic and relapse samples of 34 paediatric patients, thus identifying 125 leukaemic clones with recombinations on multiple loci (TRG, TRD, IGH and IGK), including Dd2/Dd3 and Intron/KDE rearrangements. Sequencing failures were halved (14% vs. 34%, P = 0.0007), enabling more patients to be monitored. Furthermore, more markers per patient could be monitored, reducing the probability of false negative MRD results. The whole analysis, from sample receipt to clinical validation, was shorter than our current diagnostic protocol, with equal resources. V(D)J recombination was successfully assigned by the software, even for unusual recombinations. This study emphasizes the progress that HTS with adapted bioinformatics tools can bring to the diagnosis of leukaemia patients. PMID- 26898268 TI - Solubility determination as an alternative to migration measurements. AB - Solubility values for six UV stabilisers (Cyasorb UV-1164, Tinuvin P, Tinuvin 234, Tinuvin 326, Tinuvin 327 and Tinuvin 1577) and five antioxidants (Irgafos 168, Irganox 1010, Irganox 3114, Irganox 3790 and Irganox 565) were determined in all the liquid food simulants (3% (m/V) acetic acid-water mixture, 10% (V/V), 20% (V/V), 50% (V/V) ethanol-water mixture and vegetable oil) proposed in European Union Regulation No. 10/2011/EC, as well as in fruit juice and cola drink. The applied method was obtained by modification of the method for the determination of water solubility as described in OECD guideline Test No. 105. By using ultrasonication and shorter equilibration time, the time demand of the solubility determinations were decreased notably. Solubility values proved to be lower than the specific migration limits (as specified in 10/2011/EC) at 25 degrees C for almost all target compounds in food simulants A, B, C and D1 as well as in fruit juice and cola drink. The exceptions were Tinuvin P and Irganox 3790 in simulant D1. The solubility in food simulant D2 was higher than 1000 ug ml(-1) for all target compounds. These results show that the solubility of some additives in food simulants can be so low that it makes migration studies for certain additive food simulant pairs dispensable. PMID- 26898269 TI - Chievitz' juxtaparotid organ, free from cancer. AB - INTRODUCTION: Up to the half of twentieth century, Chievitz organ was considered an embryonal organ, disappearing with growth. But Zenker, in 1953, demonstrated the existence of this organ in adult life, too4. REVIEW: In this article we review the embryology, the macroscopic and microscopic anatomy, the ultrastructure, the functional significance and the pathology of the Chievitz'Juxtaparotid Organ (CJO). The CJO is not a macroscopic apparent organ, but it looks like a nerve. The CJO takes connections with buccinator muscle, at the level of the parotid duct, and the medial pterygoid muscle. The cell parenchyma is enveloped by the connective tissue, that is divided into three layers15, 16: the inner layer -"stratum fibrosum internum"-, composed of collagenous and elastic microfibrils; the middle layer - "stratum nervosum" - containing a lamellar inner core and Ruffini SNF5; the external layer - "stratum fibrosum externum", that is a collagen capsule. The parenchymal cells show a rich enzyme activity. The parenchymal cells may play the same role as glomus cells of the 1st type and Merkel cells20, 21. When a surgical resection is performed for an oral carcinoma, the CJO may be present in the specimen25. The CJO may be wrongly diagnosed as perineural invasion by carcinoma26, 27, 28. CONCLUSION: We report that Chievitz' organ is the only organ in which the cancer does not occur. KEY WORDS: Chievitz' organ, Juxtaoral organ, Parotid gland. PMID- 26898270 TI - Facet-selective charge carrier transport, deactivation mechanism and stabilization of a Cu2O photo-electro-catalyst. AB - A facet-dependent photo-deactivation mechanism of Cu2O was verified and reported, which is caused by the facet-dependent charge carrier transport. During irradiation, the {100} and {110} crystal facets are selectively corroded by the photo-generated holes, while the {111} facets are comparatively stable. PMID- 26898271 TI - The new Sfar journals are in place. PMID- 26898272 TI - Preparation, adaptation, civism, complementarity and cohesion. PMID- 26898273 TI - The effects of a ration change from a total mixed ration to pasture on rumen fermentation, volatile fatty acid absorption characteristics, and morphology of dairy cows. AB - To investigate the effect of the change from a concentrate and silage-based ration (total mixed ration, TMR) to a pasture-based ration, a 10-wk trial (wk 1 10) was performed, including 10 rumen- and duodenum-fistulated German Holstein dairy cows (182+/-24 d in milk, 23.5+/-3.5kg of milk/d; mean +/- standard deviation). The cows were divided in either a pasture group (PG, n=5) or a confinement group (CG, n=5). The CG stayed on a TMR-based ration (35% corn silage, 35% grass silage, 30% concentrate; dry matter basis), whereas the PG was gradually transitioned from a TMR to a pasture-based ration (wk 1: TMR only; wk 2: 3 h/d on pasture wk 3 and 4: 12 h/d on pasture wk 5-10: pasture only). Ruminal pH, volatile fatty acids (VFA), NH3-N, and lipopolysaccharide (LPS) concentrations were measured in rumen fluid samples collected medially and ventrally on a weekly basis. Ruminal pH was continuously recorded during 1 to 4 consecutive days each week using ruminal pH measuring devices. In wk 1, 5, and 10, rumen contents were evacuated and weighed, papillae were collected from 3 locations in the rumen, and subsequently a VFA absorption test was performed. In the PG, mean rumen pH and molar acetate proportions decreased, and molar butyrate proportions increased continuously over the course of the trial, which can most likely be ascribed to an increased intake of rapidly fermentable carbohydrates. During the first weeks on a full grazing ration (wk 5-7), variation of rumen pH decreased, and in wk 5 a lower rumen content, papillae surface area, and potential for VFA absorption were observed. In wk 8 to 10, variation of rumen pH and total VFA concentrations increased again, and acetate/propionate ratio decreased. In wk-10 rumen content, papillae area and VFA absorption characteristics similar to initial levels were observed. Although continuous rumen pH assessments and LPS concentrations did not reveal an increased risk for subacute rumen acidosis (SARA) during the adaption period, histopathology of rumen papillae and potential for VFA absorption indicated a possible risk for rumen health. An increased risk for SARA was observed in wk 9 and 10 in the PG, but rumen LPS concentrations and histopathology were not adversely affected. Results of the present study suggest that after behavioral and metabolic adaptation to the transition from a TMR to a pasture-based ration, no adverse effects on rumen morphology and absorption capacity occurred, although rumen pH after adaptation to pasture indicated increased risk of SARA. PMID- 26898274 TI - Social stressors and their effects on immunity and health of periparturient dairy cows. AB - Management practices during the periparturient period have been the focus of much research recently because during this period immune function, metabolism, and health of cows are severely challenged. Responses to stress are often classified as behavioral, immunological, neuroendocrine, and autonomic. In production systems, understanding all facets of stress response is important to correctly predict the consequences of stressors to the health and performance of animals and to prevent costly managerial changes that have minimal effect on animal well being and performance. Common social stressors faced by periparturient animals are regrouping, overstocking, and for nulliparous animals, commingling with parous animals. In conventional dairies, feeding strategies during the periparturient period often require several group changes during the most challenging period of an animal's life. Traditional weekly regrouping of prepartum cows increases competitive behavior at the feed bunk but it does not affect immune and metabolic responses, health and production, as long as stocking density is not overwhelming, and nulliparous and parous animals are housed separately. Stocking density of prepartum animals may be overlooked because these are nonproductive animals. Severe overstocking (200% of feeding space) of commingled nulliparous and parous pregnant animals produces neuroendocrine and metabolic changes. On the other hand, when prepartum nulliparous and parous animals are housed separately, stocking densities of up to 120% do not seem to affect innate and adaptive immunity, metabolic responses, milk yield, and reproductive performance, despite increasing negative behavior among cows. In recent experiments, when animals were ranked based on feed bunk displacement, dominant animals were more likely to be diagnosed with metritis than subordinate animals. Importantly, dominant animals with large number of interactions with pen mates (displacement at the feed bunk) were considerably more likely to be diagnosed with uterine diseases (retained placenta and metritis) and to be removed from the herd within 60d postpartum. Much has been learned about behavioral responses of cows to stressful conditions, but our understanding of neuroendocrine and immune responses to such conditions is somewhat limited. A multidisciplinary approach to research that encompasses several responses to stress and biological functions is critical. PMID- 26898275 TI - Factors associated with increased milk production for automatic milking systems. AB - Automatic milking systems (AMS) are increasingly popular throughout the world. Our objective was to analyze 635 North American dairy farms with AMS for (risk) factors associated with increased milk production per cow per day and milk production per robot per day. We used multivariable generalized mixed linear regressions, which identified several significant risk factors and interactions of risk factors associated with milk production. Free traffic was associated with increased production per cow and per robot per day compared with forced systems, and the presence of a single robot per pen was associated with decreased production per robot per day compared with pens using 2 robots. Retrofitted farms had significantly less production in the first 4 yr since installation compared with production after 4 yr of installation. In contrast, newly built farms did not see a significant change in production over time since installation. Overall, retrofitted farms did not produce significantly more or less milk than newly constructed farms. Detailed knowledge of factors associated with increased production of AMS will help guide future recommendations to producers looking to transition to an AMS and maximize their production. PMID- 26898276 TI - Effect of 2 different premilking teat sanitation routines on reduction of bacterial counts on teat skin of cows on commercial dairy farms. AB - Premilking teat sanitation reduces the load of bacteria on teat skin before milking and it is a fundamental practice used to ensure collection of high quality milk. The objective of this study was to compare reduction in bacterial populations of teat skin after premilking preparation using either predipping with 0.5% iodine followed by drying (conventional; CONV) or using a semiautomated teat scrubber that uses chlorine dioxide (TS; FutureCow, Longwood, FL). Ten farms currently using a commercial teat scrubber system were enrolled. Cows (n=40 per farm) were assigned to CONV (n=198) or TS (n=196) premilking udder preparation. Teat skin swabs were collected before and after udder preparation and analyzed for total bacterial count (TBC), Streptococcus spp., Staphylococcus spp., and gram-negative bacteria (GNB). Reduction (RED) of each bacterial group was defined as the difference in the number of bacteria measured before and after udder preparation. Before udder preparation, Staphylococcus spp. (15,036 cfu/mL) and Streptococcus spp. (12,621 cfu/mL) were the most numerous microflora. Gram negative bacteria were less numerous (1,538 cfu/mL). A significant treatment by farm interaction was identified for RED of all bacterial counts. Compared with teats prepared using TS, teats prepared using CONV preparation had greater RED of TBC on 3 farms, of Streptococcus spp. on 2 farms, and of Staphylococcus spp. on 1 farm. On all other farms, RED in TBC, Streptococcus spp., and Staphylococcus spp. did not differ based on teat preparation method. Use of TS resulted in greater RED of GNB of teats on 3 farms, but RED in GNB was greater for teats cleaned by CONV on 1 farm; for the other 6 farms, RED of GNB did not differ between methods. For all bacterial counts, an effect of chlorine dioxide concentration used in the teat scrubber was observed. Results from this study suggest both CONV and TS can effectively reduce bacterial counts, but farm conditions and management practices can have a significant effect on the effectiveness of teat disinfection. PMID- 26898277 TI - Using automated feeders to wean calves fed large amounts of milk according to their ability to eat solid feed. AB - Dairy calves weaned off milk at an early age show signs of hunger and can lose weight. We examined whether using automated feeders to wean calves according to individual voluntary solid feed intake reduced the effects of weaning. Female Holstein calves were housed in groups of 5 to 9. All calves were fed 12 L/d milk and ad libitum grain starter and hay from automated feeders immediately after grouping, and were allocated to 3 weaning strategies: (1) early-weaned (EW; n=14): weaning began on d 40, and milk allowance gradually decreased until weaning was complete on d 48; (2) late-weaned (LW; n=14): weaning began on d 80 and was completed on d 89; (3) weaned by starter intake (WSI; n=28): weaning began when calves consumed 200g/d of starter and was completed when the calves consumed 1,400g/d. Each day, the automated feeders recorded quantities of milk, starter, and hay eaten by all calves, as well as the frequency of visits to the milk feeder; we used unrewarded visit frequency as a sign of hunger. Body weights (BW) were recorded weekly. We estimated daily digestible energy (DE) intake for each calf based on the milk, hay, and starter consumed. Average daily gains (ADG) were expressed as percent of BW. For calves in WSI, weaning began at 54.7+/-18.9 d (mean +/- SD) of age, the duration of weaning was 21.1+/-10.6 d, and weaning ended at 75.8+/-10.7 d of age. Both LW and WSI calves had better ADG from wk 3 to 13 than EW calves. Calves in the WSI group drank less milk and ate more starter than LW calves but had similar ADG. During the period of weaning, EW calves made more unrewarded visits to the milk feeder than LW and WSI calves. Three EW calves lost weight during weaning, whereas all LW and WSI calves gained weight. Calves differ greatly in when they begin to eat solid feed and how quickly they increase the intake in response to a decrease in milk allowance. An advantage of automated feeders is that calves can be weaned at variable ages depending on their ability and willingness to eat solid feed, which reduces signs of hunger and improves weight gains during weaning. PMID- 26898278 TI - Effectiveness of mid-infrared spectroscopy to predict the color of bovine milk and the relationship between milk color and traditional milk quality traits. AB - The color of milk affects the subsequent color features of the resulting dairy products; milk color is also related to milk fat concentration. The objective of the present study was to quantify the ability of mid-infrared spectroscopy (MIRS) to predict color-related traits in milk samples and to estimate the correlations between these color-related characteristics and traditional milk quality traits. Mid-infrared spectral data were available on 601 milk samples from 529 cows, all of which had corresponding gold standard milk color measures determined using a Chroma Meter (Konica Minolta Sensing Europe, Nieuwegein, the Netherlands); milk color was expressed using the CIELAB uniform color space. Separate prediction equations were developed for each of the 3 color parameters (L*=lightness, a*=greenness, b*=yellowness) using partial least squares regression. Accuracy of prediction was determined using both cross validation on a calibration data set (n=422 to 457 samples) and external validation on a data set of 144 to 152 samples. Moderate accuracy of prediction was achieved for the b* index (coefficient of correlation for external validation=0.72), although poor predictive ability was obtained for both a* and L* indices (coefficient of correlation for external validation of 0.30 and 0.55, respectively). The linear regression coefficient of the gold standard values on the respective MIRS predicted values of a*, L*, and b* was 0.81, 0.88, and 0.96, respectively; only the regression coefficient on L* was different from 1. The mean bias of prediction (i.e., the average difference between the MIRS-predicted values and gold standard values in external validation) was not different from zero for any of 3 parameters evaluated. A moderate correlation (0.56) existed between the MIRS predicted L* and b* indices, both of which were weakly correlated with the a* index. Milk fat, protein, and casein were moderately correlated with both the gold standard and MIRS-predicted values for b*. Results from the present study indicate that MIRS data provides an efficient, low-cost screening method to determine the b* color of milk at a population level. PMID- 26898279 TI - Feedback effects of estradiol and progesterone on ovulation and fertility of dairy cows after gonadotropin-releasing hormone-induced release of luteinizing hormone. AB - An experiment was conducted with the objective to determine the effects of estradiol, progesterone, presence of a corpus luteum (CL), and size of a dominant follicle on the characteristics and patterns of GnRH-induced LH release and subsequent ovulation during a timed artificial insemination (TAI) program, or a combination of these. In 70 lactating dairy cows, a total of 163 blood collection periods resulting in a GnRH-induced LH release were analyzed. Concentrations of LH were measured in hourly samples (0 through 6 h after GnRH) during each of the blood collection periods, whereas concentrations of progesterone and estradiol were measured in the sample before GnRH treatment (0 h). Measures of LH included time to LH peak concentration during the 6-h blood collection period, the 2 largest concentrations of LH, mean, and variance of the 6 LH concentrations under each LH curve. Individual and combination effects of CL presence and a dominant follicle <= or >13.5mm, in addition to individual and combination effects of progesterone: low (<0.45 ng/mL; n=83), medium (0.53 to 2.41 ng/mL; n=25), and high (2.66 to 10.7 ng/mL; n=55), and estradiol: low (<4.0 pg/mL; n=89) and high (>=4.0 pg/mL; n=74) were independent variables in models to determine their influence on characteristics of LH and ovulation. Injections of GnRH induced LH release during 6 h after each of 163 injections. Measures of GnRH-induced LH concentration were inhibited at greater concentrations of progesterone and in the presence of a CL. In contrast, GnRH-induced LH concentrations were increased when estradiol was >=4.0 pg/mL, but relatively unaffected by the size of the dominant follicle. Furthermore, resulting incidences of ovulation were decreased at greater progesterone concentrations and presence of a CL, and increased at greater estradiol concentrations and presence of follicles >13.5mm. In cows with or without a CL, the presence of a follicle >13.5mm did not increase mean LH concentration or incidence of ovulation. We conclude that when progesterone concentration exceeded 0.5 ng/mL at the time of GnRH treatment, subsequent LH concentrations and ovulation were suppressed. At that same concentration of progesterone or when concentrations of estradiol were >=4 pg/mL, TAI pregnancy outcomes were improved in the face of similar incidences of ovulation suggesting greater progesterone or lesser estradiol at the time of AI may inhibit pregnancy establishment by other mechanisms. PMID- 26898280 TI - Bacterial subclinical mastitis and its effect on milk yield in low-input dairy goat herds. AB - The objectives of this study were (1) to record the major pathogens associated with subclinical mastitis (SCM), (2) to calculate their incidence during the milking period, and (3) to estimate the effect of SCM on daily milk yield (DMY) for goats reared under low-input management schemes. Dairy goats (n=590) of Skopelos and indigenous Greek breeds from 4 herds were randomly selected for the study. The study included monthly monitoring, milk yield recording, and bacteriological analyses of milk of individual goats during the course of 2 successive milking periods. Incidence and cumulative incidence were calculated for SCM cases. Moreover, 2 mixed linear regression models were built to assess the effects of (1) SCM and (2) different pathogens isolated from SCM cases, on DMY. The estimated incidence and cumulative incidence of SCM for the first and the second year of the study were 69.5 and 96.4 new cases of SCM/1,000 goat months, and 24.1 and 31.7%, respectively. A total of 755 milk samples were subjected to microbiological examination, resulting in 661 positive cultures. Coagulase-negative and coagulase-positive staphylococci were isolated from 50.2 and 34.5% of the positive cultures, respectively. The incidence of infections (new infections per 1,000 goat-months) for the first and the second year of the study were 34 and 53 for coagulase-negative staphylococci, 23 and 28 for coagulase-positive staphylococci, 3 and 5 for Streptococcus/Enterococcus spp., and 5.5 and 9.1 for gram-negative bacteria. Goats with SCM had lower DMY when compared with goats without SCM (ca. 47g/d, corresponding to a 5.7% decrease in DMY). In particular, goats with SCM due to coagulase-positive staphylococci infection produced approximately 80g/d less milk (a reduction of ca. 9.7%) compared with uninfected ones, whereas SCM due to gram-negative bacteria resulted in approximately 15% reduction in DMY. Investigating the epidemiology of SCM and its effects on production traits is critical for the establishment of effective preventive measures against SCM and for the assessment of the sustainability of production in low-input dairy goat herds. PMID- 26898281 TI - Effect of duration of milk accumulation in the udder on milk composition, especially on milk fat globule. AB - Our objective was to study the effect of duration of milk accumulation on milk fat globules (MFG) secretion to better understand relationships between milk yield, milk fat, and MFG secretion. The modification of the milk accumulation duration in the udder is a tool to increase milk fat content. Four milking frequencies were studied on 6 dairy cows averaging 118+/-22 d in milk: 2 milkings/d separated by 11- and 13-h or by 4- and 20-h intervals and 1 milking/d. The experimental trial was a double Latin square 3*3 with 2-wk periods. Postexperiment, a milking frequency of 36-h was repeated twice. Compared with 2 milkings with 11- and 13-h frequencies, 1 milking/d reduced milk and milk fat yields and increased fat content, without any effect on the size of MFG. Two milkings with 4- and 20-h intervals had no significant effect on milk fat yield and content but tended to increase the size of the MFG. Lipolysis, measured on morning milk, was weaker with 1 milking/d. When data were analyzed according to milk accumulation duration (4, 11, 13, 20, 24, and 36h), the highest fat content and the largest diameters of MFG were obtained on milks from 4 and 36h milkings (62.8g/kg, 4.15 um and 57.7g/kg, 4.09 um, respectively). Such observations could have 2 origins: the richness in residual milk of the 4-h milk and the coalescence of MFG related to the long milk accumulation duration in the 36-h milk. For each duration of milk accumulation, a relationship exists between MFG size and fat yield. The positive relation between MFG size and fat content was confirmed at each duration of milk accumulation. Rate of secretion of milk fat (milk accumulation of 4h excluded) was also well correlated with MFG size. For the 36-h milk, this relationship was also observed but with a significantly different slope, assuming phenomena of MFG coalescence in response to the supposed increased intramammary pressure or to slower secretion rate and, hence, fusion events of microlipids droplets in the cytoplasm. Duration of milk accumulation joined with large increases in milk fat content induces changes in MFG size. PMID- 26898283 TI - The effect of different composition of ternary mixtures of emulsifying salts on the consistency of processed cheese spreads manufactured from Swiss-type cheese with different degrees of maturity. AB - The scope of this work was to investigate the dependence of selected textural (texture profile analysis, TPA) and viscoelastic properties of processed cheese on the composition of ternary mixtures of emulsifying salts [disodium hydrogenphosphate, DSP; tetrasodium diphosphate, TSPP; sodium salt of polyphosphate (with mean length n ~ 20), P20; and trisodium citrate, TSC] during a 60-d storage period (6+/-2 degrees C). The processed cheese samples [40% wt/wt dry matter (DM) content, 50% wt/wt fat in DM content] were manufactured using Swiss-type cheese (as the main raw material) with 4 different maturity degrees (4, 8, 12, and 16 wk of ripening). Moreover, the pH of the samples was adjusted (the target values within the range of 5.60-5.80), corresponding to the standard pH values of spreadable processed cheese. With respect to the individual application of emulsifying salts (regardless of the maturity degree of the Swiss type cheese applied), the samples prepared with P20 were the hardest, followed by those prepared with TSPP, TSC, and DSP. Furthermore, a specific ratio of DSP:TSPP (1:1) led to a significant increase in the hardness of the samples. On the whole, the hardness of all processed cheese samples increased with the prolonging storage period, whereas their hardness significantly dropped with the rising ripening stage of the raw material utilized. In all of the cases, the trends of hardness development remained analogous, and only the absolute values differed significantly. Moreover, the findings of TPA were in accordance with those of the rheological analysis. In particular, the specific ratio of DSP:TSPP (1:1) resulted in the highest gel strength and interaction factor values, followed by P20, TSPP, TSC, and DSP (used individually), reporting the same trend which was demonstrated by TPA. The monitored values of the gel strength and interaction factor decreased with the increasing maturity degree of the Swiss-type cheese used. The intensity of the rigidity of the samples showed an analogous relationship to the intensity of the gel strength; the higher the gel strength of the sample, the more inflexible the product is expected to be. PMID- 26898282 TI - Prepartum supplementation of nicotinic acid: Effects on health of the dam, colostrum quality, and acquisition of immunity in the calf. AB - Nicotinic acid (NA) has been shown to reduce lipolysis, alter milk components and the ruminal environment, and increase blood flow. Increased blood flow to the mammary gland during colostrogenesis might increase nutrients and immunoglobulin concentration of colostrum. Twenty-six multiparous Holstein cows were housed in a tiestall barn. Cows were blocked by expected calving date and randomly assigned to 1 of 2 treatments 4 wk prepartum: (1) 0g/d of NA (control, CON) or (2) 48g/d of NA (NA). Total mixed ration amounts fed and refused were measured daily to determine dry matter intake. Blood samples were collected from dams every Monday, Wednesday, and Friday from the coccygeal vein or artery and were analyzed for glucose, nonesterified fatty acids (NEFA), and beta-hydroxybutyrate (BHB). Colostrum was collected and weighed within 90 min of parturition. Colostral immunoglobulin G (IgG) concentration was analyzed using radial immunodiffusion assay. Calves were removed from their dams before suckling and weighed within 30 min after birth. Calves received 3 L of a lacteal-based colostrum replacer that provided a total of 225.8g of IgG within 2h of birth. Calf blood samples were collected via jugular venipuncture at 0 and 24h of age and analyzed for IgG concentration and determination of apparent efficiency of absorption. Colostrum yield, dry matter intake, IgG yield, and fat and solids percentage of colostrum did not differ between treatments. Serum concentrations of glucose and BHB were not affected by treatment. We detected an effect of week on serum glucose concentrations at calving and on serum BHB concentrations at 1 wk postpartum. There was a treatment by week effect for serum NEFA concentrations at 1 wk postpartum, where cows that received NA prepartum had higher serum NEFA concentration than CON cows, indicating that a NEFA rebound occurred. No differences were observed for calf body weight, 0- or 24-h serum IgG concentration, or apparent efficiency of absorption. Supplementation of NA increased IgG concentration in colostrum from 73.8 to 86.8g/L. Results indicate that 48g/d of supplemental NA during the prepartum period improved colostrum quality. PMID- 26898284 TI - Effects of the diacylglycerol o-acyltransferase 1 (DGAT1) K232A polymorphism on fatty acid, protein, and mineral composition of dairy cattle milk. AB - Several studies have described associations between the diacylglycerol o acyltransferase 1 (DGAT1) K232A polymorphism and routinely collected milk production traits but not much is known about effects of the DGAT1 polymorphism on detailed milk composition. The aim of this study was to estimate effects of the DGAT1 polymorphism on milk fatty acid, protein, and mineral composition. We looked for effects that were significant and consistent in Danish Holstein Friesian (HF), Danish Jersey, and Dutch HF as these are likely to be true effects of the DGAT1 K232A polymorphism rather than being effects of linked loci. For fatty acid composition, significant and consistent effects of the DGAT1 polymorphism were detected on C14:0, C16:0, C15:0, C16:1, C18:1 cis-9, conjugated linoleic acid (CLA) cis-9,trans-11, C18:2 cis-9,cis-12, and C18:3 cis-9,cis 12,cis-15 content (percent by weight, wt/wt %). For C16:0, C16:1, and C18:1 cis 9, the DGAT1 polymorphism explained more than 10% of the phenotypic variation. Significant effects on milk protein composition in Dutch HF could not be confirmed in Danish Jersey or Danish HF. For mineral content, significant and consistent effects of the DGAT1 polymorphism on calcium, phosphorus, and zinc were detected. In the Dutch HF population, the contribution of the DGAT1 K232A polymorphism to phenotypic variance was 12.0% for calcium, 8.3% for phosphorus, and 6.1% for zinc. Different from effects on fatty acid composition, effects of the DGAT1 polymorphism on yields of long-chain fatty acids C18:1 cis-9, CLA cis 9,trans-11, C18:2 cis-9,cis-12, and C18:3 cis-9,cis-12,cis-15 were not significant. This indicates that effects of DGAT1 on these fatty acids are indirect, not direct, effects: DGAT1 affects de novo synthesis of fatty acids and, consequently, the contribution of the long-chain fatty acids to total fat is decreased. In addition, effects of the DGAT1 polymorphism on yields of Ca, P, and Zn were not significant, which indicates that effects on these minerals are the result of indirect rather than direct effects of DGAT1: effects on calcium, phosphorus, and zinc content can be explained by effects of DGAT1 on milk volume. The reported effects of the DGAT1 polymorphism on fatty acid and mineral composition of milk are substantial and therefore relevant for milk quality. PMID- 26898285 TI - The multi-year cumulative effects of alternative stocking rate and grazing management practices on pasture productivity and utilization efficiency. AB - The production and utilization of increased quantities of high quality pasture is of paramount importance in pasture-based milk production systems. The objective of this study was to evaluate the cumulative effects of alternative integrated grazing strategies, incorporating alternative stocking rate (SR) and grazing severities, on pasture productivity and grazing efficiency over multiple years within farm systems using perennial ryegrass dominant pastures. Three whole-farm SR treatments were compared over 4 complete grazing seasons (2009 to 2012 inclusive): low (2.51 cows/ha; LSR), medium (2.92 cows/ha; MSR), and high (3.28 cows/ha; HSR). Each system had its own farmlet containing 18 paddocks and remained on the same treatment for the duration of the study. Stocking rate had a significant effect on all grazing variables with the exception of soil fertility status and sward density. Increased SR resulted in increased total annual net pasture accumulation, improved sward nutritive value, and increased grazed pasture utilization. Total annual net pasture accumulation was greatest in HSR [15,410kg of dry matter (DM)/ha], intermediate for MSR (14,992kg of DM/ha), and least for LSR (14,479kg of DM/ha) during the 4-yr study period. A linear effect of SR on net pasture accumulation was detected with an increase in net pasture accumulation of 1,164.4 (SE=432.7) kg of DM/ha for each 1 cow/ha increase in SR. Pregrazing pasture mass and height and postgrazing residual pasture mass and height were greatest for LSR, intermediate for the MSR, and lowest for the HSR. In comparison with the LSR, the imposition of a consistently increased grazing severity coupled with increased whole farm SR in MSR and HSR treatments arrested the decline in sward nutritive value, typically observed during mid-season. Incorporating the individual beneficial effects of SR on pasture accumulation, nutritive value, and utilization efficiency, total proportional energy (unite fourragere lait) utilization per hectare increased significantly with increasing SR (+0.026 and +0.081 for MSR and HSR, respectively). These results quantify the significant effect of grazing management practices on the feed production capability of modern perennial ryegrass pastures for intensive grazing dairy production systems. Furthermore, these results highlight the importance of consistently imposing grazing treatments over multiple years, and within integrated whole farm systems, to accurately assess the longer term effects of alternate grazing management practices on pasture productivity. PMID- 26898286 TI - Growth, intake, and health of Holstein heifer calves fed an enhanced preweaning diet with or without postweaning exogenous estrogen. AB - Research has shown that changes in nutrition both before and after weaning can affect mammary development. Additionally, estrogen is known to be a potent mammogenic stimulant. Our objectives were to determine effects of altered preweaning feeding and exogenous estradiol postweaning on growth, intake, and health. Thirty-six Holstein heifer calves were reared on (1) a restricted milk replacer (MR) diet fed at 0.44kg powder dry matter (DM)/day [R; 20.9% crude protein (CP), 19.8% fat, DM basis], or (2) an enhanced MR fed at 1.08kg powder DM/d (EH; 28.9% CP, 26.2% fat, DM basis). The MR feeding was reduced 50% during wk 8 to prepare for weaning. Starter was offered after wk 4 but balanced between treatments. Body weight and frame were measured weekly with intakes and health monitored daily. At weaning, a subset of calves were slaughtered (n=6/diet). Enhanced-fed calves had greater carcass, thymus, liver, spleen, and mammary gland (parenchyma and mammary fat pad) weights. The EH calves also had greater average daily gain (ADG) starting during wk 1 (0.36 vs. -0.06kg/d) and lasting through wk 7 (1.00 vs. 0.41kg/d). Remaining calves received estrogen implants or placebo and were slaughtered at the end of wk 10, creating 4 treatments: (1) R, (2) R + estrogen (R-E2), (3) EH, and (4) EH + estrogen (EH-E2). Postweaning ADG was similar between R, EH, and EH-E2 calves, but greater in R-E2 calves than E calves. The EH-E2 calves had the heaviest mammary glands, and R-E2 calves had heavier mammary glands than R calves. The EH calves consumed more MR DM, CP, and fat preweaning. The R-fed calves consumed more starter DM preweaning. Fecal score was greater for EH calves (1.74 vs. 1.50) preweaning, but days medicated did not differ. Fecal scores were lower for R-E2 calves postweaning. Improved preweaning feeding of calves increased body weights and frame measures. Differences in body weights remained postweaning. Enhanced-fed calves showed greater ADG during the preweaning period but not postweaning. Exogenous estrogen may elicit diet dependent growth responses. Analysis of collected samples will allow determination of cellular and molecular processes responsible for the marked differences in mammary development observed. PMID- 26898287 TI - Intramammary infections and milk leakage following gradual or abrupt cessation of milking. AB - The objective of this study was to evaluate the effect of milking cessation method (abrupt or gradual) and daily milk yield before dry-off on milk leakage following dry-off and intramammary infections (IMI) at calving. Data from 1,086 quarters of 285 cows from 5 Ohio dairy herds were analyzed. All cows that were due to be dried off within a week were assigned to the same study group to facilitate management. Abrupt-cessation cows kept the farm's regular milking schedule through dry-off, and gradual-cessation cows were milked once daily for the final week of lactation. Aseptic technique was used to collect quarter foremilk samples at the time of enrollment (7 to 14 d before expected dry-off), the final milking before dry-off (D-O), and within 7 d of calving. Cows in the gradual-cessation group were observed for milk leakage during the period of once daily milking. In the only herd that did not use internal teat sealants at dry off, milk leakage after dry-off was recorded in both abrupt and gradual groups. Gradual cessation decreased milk production by 33.4% during the final week of lactation, causing milk yield at D-O to be lower for these cows compared with abrupt-cessation cows (13.2 vs. 19.8kg/d, respectively). Logistic regression models were used to model the probability of a quarter being infected at calving with any pathogen, accounting for clustering of quarters within cows and cows within herds. The final model investigating the probability of IMI at calving was stratified by parity of cows at the time of dry-off (primiparous and multiparous). Among quarters of cows that ended their first lactation, abrupt cessation of milking before dry-off and milk leakage after dry-off were associated with an increased risk of IMI at calving. Among quarters of multiparous cows, on the other hand, gradual cessation of milking before dry-off, presence of IMI at D-O, and thrice-daily milking during lactation increased the odds of IMI at calving. These results indicate that implementation of differing management practices near dry-off for different parity groups may improve mammary health within a herd. PMID- 26898288 TI - Inclusion of sainfoin (Onobrychis viciifolia) silage in dairy cow rations affects nutrient digestibility, nitrogen utilization, energy balance, and methane emissions. AB - Sainfoin (Onobrychis viciifolia) is a tanniniferous legume forage that has potential nutritional and health benefits preventing bloating, reducing nematode larval establishment, improving N utilization, and reducing greenhouse gas emissions. However, the use of sainfoin as a fodder crop in dairy cow rations in northwestern Europe is still relatively unknown. The objective of this study was to evaluate the effect of sainfoin silage on nutrient digestibility, animal performance, energy and N utilization, and CH4 production. Six rumen-cannulated, lactating dairy cows with a metabolic body weight (BW(0.75)) of 132.5+/-3.6kg were randomly assigned to either a control (CON) or a sainfoin (SAIN)-based diet over 2 experimental periods of 25 d each in a crossover design. The CON diet was a mixture of grass silage, corn silage, concentrate, and linseed. In the SAIN diet, 50% of grass silage dry matter (DM) of the CON diet was exchanged for sainfoin silage. The cows were adapted to 95% of ad libitum feed intake for a 21 d period before being housed in climate-controlled respiration chambers for 4 d, during which time feed intake, apparent total-tract digestibility, N and energy balance, and CH4 production was determined. Data were analyzed using a mixed model procedure. Total daily DM, organic matter, and neutral detergent fiber intake did not differ between the 2 diets. The apparent digestibility of DM, organic matter, neutral detergent fiber, and acid detergent fiber were, respectively, 5.7, 4.0, 15.7, and 14.8% lower for the SAIN diet. Methane production per kilogram of DM intake was lowest for the SAIN diet, CH4 production as a percentage of gross energy intake tended to be lower, and milk yield was greater for the SAIN diet. Nitrogen intake, N retention, and energy retained in body protein were greater for the SAIN than for the CON diet. Nitrogen retention as a percentage of N intake tended to be greater for the SAIN diet. These results suggest that inclusion of sainfoin silage in dairy cow rations reduces CH4 per kilogram of DM intake and nutrient digestibility. Moreover, sainfoin silage improves milk production and seems to redirect metabolism toward body protein accretion at the expense of body fat. PMID- 26898291 TI - Indomethacin inhibits tetrodotoxin-resistant Na(+) channels at acidic pH in rat nociceptive neurons. AB - Non-steroidal anti-inflammatory drugs (NSAIDs) are well-known inhibitors of cyclooxygenases (COXs) and are widely used for the treatment of inflammatory pain; however several NSAIDs display COX-independent analgesic action including the inhibition of voltage-gated Na(+) channels expressed in primary afferent neurons. In the present study, we examined whether NSAIDs modulate tetrodotoxin resistant (TTX-R) Na(+) channels and if this modulation depends on the extracellular pH. The TTX-R Na(+) currents were recorded from small-sized trigeminal ganglion neurons by using a whole-cell patch clamp technique. Among eight NSAIDs tested in this study, several drugs, including aspirin and ibuprofen, did not affect TTX-R Na(+) channels either at pH 7.4 or at pH 6.0. However, we found that indomethacin, and, to a lesser extent, ibuprofen and naproxen potently inhibited the peak amplitude of TTX-R Na(+) currents at pH 6.0. The indomethacin-induced inhibition of TTX-R Na(+) channels was more potent at depolarized membrane potentials. Indomethacin significantly shifted both the voltage-activation and voltage-inactivation relationships to depolarizing potentials at pH 6.0. Indomethacin accelerated the development of inactivation and retarded the recovery from inactivation of TTX-R Na(+) channels at pH 6.0. Given that indomethacin and several other NSAIDs could further suppress local nociceptive signals by inhibiting TTX-R Na(+) channels at an acidic pH in addition to the classical COX inhibition, these drugs could be particularly useful for the treatment of inflammatory pain. PMID- 26898289 TI - Evaluation of the effect of valence state on cerium oxide nanoparticle toxicity following intratracheal instillation in rats. AB - Cerium (Ce) is becoming a popular metal for use in electrochemical applications. When in the form of cerium oxide (CeO2), Ce can exist in both 3 + and 4 + valence states, acting as an ideal catalyst. Previous in vitro and in vivo evidence have demonstrated that CeO2 has either anti- or pro-oxidant properties, possibly due to the ability of the nanoparticles to transition between valence states. Therefore, we chose to chemically modify the nanoparticles to shift the valence state toward 3+. During the hydrothermal synthesis process, 10 mol% gadolinium (Gd) and 20 mol% Gd, were substituted into the lattice of the CeO2 nanoparticles forming a perfect solid solution with various A-site valence states. These two Gd doped CeO2 nanoparticles were compared to pure CeO2 nanoparticles. Preliminary characteristics indicated that doping results in minimal size and zeta potential changes but alters valence state. Following characterization, male Sprague-Dawley rats were exposed to 0.5 or 1.0 mg/kg nanoparticles via a single intratracheal instillation. Animals were sacrificed and bronchoalveolar lavage fluid and various tissues were collected to determine the effect of valence state and oxygen vacancies on toxicity 1-, 7-, or 84-day post-exposure. Results indicate that damage, as measured by elevations in lactate dehydrogenase, occurred within 1-day post-exposure and was sustained 7-day post-exposure, but subsided to control levels 84-day post-exposure. Furthermore, no inflammatory signaling or lipid peroxidation occurred following exposure with any of the nanoparticles. Our results implicate that valence state has a minimal effect on CeO2 nanoparticle toxicity in vivo. PMID- 26898292 TI - Blockade of the spinal BDNF-activated JNK pathway prevents the development of antiretroviral-induced neuropathic pain. AB - Although antiretroviral agents have been used successfully in suppressing viral production, they have also been associated with a number of side effects. The antiretroviral toxic neuropathy induces debilitating and extremely difficult to treat pain syndromes that often lead to discontinuation of antiretroviral therapy. Due to the critical need for the identification of novel therapeutic targets to improve antiretroviral neuropathic pain management, we investigated the role of the JNK signalling pathway in the mechanism of antiretroviral painful neuropathy. Mice were exposed to zalcitabine (2',3'-dideoxycytidine, ddC) and stavudine (2',3'-didehydro-3'-deoxythymidine, d4T) that induced a persistent mechanical allodynia and a transient cold allodynia. Treatment with the JNK blocker SP600125 before antiretroviral administration abolished mechanical hypersensitivity with no effect on thermal response. A robust spinal JNK overphosphorylation was observed on post-injection day 1 and 3, along with a JNK dependent increase in p-c-Jun and ATF3 protein levels. Co-immunoprecipitation experiments showed the presence of a heterodimeric complex between ATF3 and c-Jun indicating that these transcription factors can act together to regulate transcription through heterodimerization. A rise in BDNF and caspase-3 protein levels was detected on day 1 and BDNF sequestration prevented both caspase-3 and p-JNK increase. These data suggest that BDNF plays a role in the early stages of ddC-induced allodynia by promoting apoptotic events and the activation of a hypernociceptive JNK-mediated pathway. We illustrated the activation of a BDNF mediated JNK pathway involved in the early events responsible for the promotion of neuropathic pain, leading to a better knowledge of the mechanisms involved in the antiretroviral neuropathy. SUMMARY: JNK blockade prevents antiretroviral induced pain hypersensitivity. This may represent a potential prophylactic treatment of neuropathic pain to improve antiretroviral tolerability. PMID- 26898293 TI - Pilot Experience with an External Quality Assurance Scheme for Acylcarnitines in Plasma/Serum. AB - The analysis of acylcarnitines (AC) in plasma/serum is established as a useful test for the biochemical diagnosis and the monitoring of treatment of organic acidurias and fatty acid oxidation defects. External quality assurance (EQA) for qualitative and quantitative AC is offered by ERNDIM and CDC in dried blood spots but not in plasma/serum samples. A pilot interlaboratory comparison between 14 European laboratories was performed over 3 years using serum/plasma samples from patients with an established diagnosis of an organic aciduria or fatty acid oxidation defect. Twenty-three different samples with a short clinical description were circulated. Participants were asked to specify the method used to analyze diagnostic AC, to give quantitative data for diagnostic AC with the corresponding reference values, possible diagnosis, and advice for further investigations.Although the reference and pathological concentrations of AC varied among laboratories, elevated marker AC for propionic acidemia, isovaleric acidemia, medium-chain acyl-CoA dehydrogenase, very long-chain acyl-CoA dehydrogenase, and multiple acyl-CoA dehydrogenase deficiencies were correctly identified by all participants allowing the diagnosis of these diseases. Conversely, the increased concentrations of dicarboxylic AC were not always identified, and therefore the correct diagnosis was not reach by some participants, as exemplified in cases of malonic aciduria and 3-hydroxy-3 methylglutaryl-CoA lyase deficiency. Misinterpretation occurred in those laboratories that used multiple-reaction monitoring acquisition mode, did not derivatize, or did not separate isomers. However, some of these laboratories suggested further analyses to clarify the diagnosis.This pilot experience highlights the importance of an EQA scheme for AC in plasma. PMID- 26898294 TI - Treatment with Mefolinate (5-Methyltetrahydrofolate), but Not Folic Acid or Folinic Acid, Leads to Measurable 5-Methyltetrahydrofolate in Cerebrospinal Fluid in Methylenetetrahydrofolate Reductase Deficiency. AB - S-adenosyl methionine, which is formed from methionine, is an essential methyl donor within the central nervous system. Methionine is formed by the enzyme methionine synthase for which 5-methyltetrahydrofolate (5-MTHF) and homocysteine are substrates. Patients with severe methylenetetrahydrofolate reductase (MTHFR) deficiency cannot make 5-MTHF and have extremely low levels in the CSF. As a consequence, methylation reactions in the CNS are compromised, and this is likely to play an important role in the neurological abnormalities that occur in MTHFR deficiency. Although treatment with oral betaine can remethylate homocysteine to methionine in the liver, betaine crosses the blood-brain barrier poorly, and CSF levels of methionine remain low. We report three patients with severe MTHFR deficiency (enzyme activity <=1% of controls) who had undetectable levels of CSF 5-MTHF at diagnosis and while on treatment with either folic acid or calcium folinate. Only treatment with oral 5-MTHF given as calcium mefolinate at doses of 15-60 mg/kg/day resulted in an increase in CSF 5-MTHF. PMID- 26898295 TI - Genome-wide identification and homeolog-specific expression analysis of the SnRK2 genes in Brassica napus guard cells. AB - Sucrose non-fermenting-1-related protein kinase 2 (SnRK2) proteins constitute a small plant-specific serine/threonine kinase family involved in abscisic acid (ABA) signaling and plant responses to biotic and abiotic stresses. Although SnRK2s have been well-studied in Arabidopsis thaliana, little is known about SnRK2s in Brassica napus. Here we identified 30 putative sequences encoding 10 SnRK2 proteins in the B. napus genome and the expression profiles of a subset of 14 SnRK2 genes in guard cells of B. napus. In agreement with its polyploid origin, B. napus maintains both homeologs from its diploid parents. The results of quantitative real-time PCR (qRT-PCR) and reanalysis of RNA-Seq data showed that certain BnSnRK2 genes were commonly expressed in leaf tissues in different varieties of B. napus. In particular, qRT-PCR results showed that 12 of the 14 BnSnRK2s responded to drought stress in leaves and in ABA-treated guard cells. Among them, BnSnRK2.4 and BnSnRK2.6 were of interest because of their robust responsiveness to ABA treatment and drought stress. Notably, BnSnRK2 genes exhibited up-regulation of different homeologs, particularly in response to abiotic stress. The homeolog expression bias in BnSnRK2 genes suggests that parental origin of genes might be responsible for efficient regulation of stress responses in polyploids. This work has laid a foundation for future functional characterization of the different BnSnKR2 homeologs in B. napus and its parents, especially their functions in guard cell signaling and stress responses. PMID- 26898296 TI - Beneficial effects of bacteria-plant communication based on quorum sensing molecules of the N-acyl homoserine lactone group. AB - Bacterial quorum sensing (QS) mechanisms play a crucial role in the proper performance and ecological fitness of bacterial populations. Many key physiological processes are regulated in a QS-dependent manner by auto-inducers, like the N-acyl homoserine lactones (AHLs) in numerous Gram-negative bacteria. In addition, also the interaction between bacteria and eukaryotic hosts can be regulated by AHLs. Those mechanisms gained much attention, because of the positive effects of different AHL molecules on plants. This positive impact ranges from growth promotion to induced resistance and is quite contrasting to the rather negative effects observed in the interactions between bacterial AHL molecules and animals. Only very recently, we began to understand the molecular mechanisms underpinning plant responses to AHL molecules. In this review, we gathered the latest information in this research field. The first part gives an overview of the bacterial aspects of quorum sensing. Later we focus on the impact of AHLs on plant growth and AHL-priming, as one of the most understood phenomena in respect to the inter-kingdom interactions based on AHL-quorum sensing molecules. Finally, we discuss the potential benefits of the understanding of bacteria-plant interaction for the future agricultural applications. PMID- 26898297 TI - Toll-Like Receptor 4 Deficiency Causes Reduced Exploratory Behavior in Mice Under Approach-Avoidance Conflict. AB - Abnormal approach-avoidance behavior has been linked to deficits in the mesolimbic dopamine (DA) system of the brain. Recently, increasing evidence has indicated that toll-like receptor 4 (TLR4), an important pattern-recognition receptor in the innate immune system, can be directly activated by substances of abuse, resulting in an increase of the extracellular DA level in the nucleus accumbens. We thus hypothesized that TLR4-dependent signaling might regulate approach-avoidance behavior. To test this hypothesis, we compared the novelty seeking and social interaction behaviors of TLR4-deficient (TLR4(-/-)) and wild type (WT) mice in an approach-avoidance conflict situation in which the positive motivation to explore a novel object or interact with an unfamiliar mouse was counteracted by the negative motivation to hide in exposed, large spaces. We found that TLR4(-/-) mice exhibited reduced novelty-seeking and social interaction in the large open spaces. In less stressful test apparatuses similar in size to the mouse cage, however, TLR4(-/-) mice performed normally in both novelty-seeking and social interaction tests. The reduced exploratory behaviors under approach-avoidance conflict were not due to a high anxiety level or an enhanced fear response in the TLR4(-/-) mice, as these mice showed normal anxiety and fear responses in the open field and passive avoidance tests, respectively. Importantly, the novelty-seeking behavior in the large open field induced a higher level of c-Fos activation in the nucleus accumbens shell (NAcSh) in TLR4( /-) mice than in WT mice. Partially inactivating the NAcSh via infusion of GABA receptor agonists restored the novelty-seeking behavior of TLR4(-/-) mice. These data suggested that TLR4 is crucial for positive motivational behavior under approach-avoidance conflict. TLR4-dependent activation of neurons in the NAcSh may contribute to this phenomenon. PMID- 26898299 TI - Population pharmacokinetics and exposure-response relationship of amatuximab, an anti-mesothelin monoclonal antibody, in patients with malignant pleural mesothelioma and its application in dose selection. AB - PURPOSE: To characterize amatuximab pharmacokinetics (PK) and the relationship of amatuximab exposure with response in patients with unresectable malignant pleural mesothelioma (MPM) receiving amatuximab with pemetrexed and cisplatin. METHODS: A nonlinear mixed effects PK model was built using data from all of the amatuximab studies conducted to date. Patients received amatuximab alone or in combination with chemotherapy. The influence of demographic, laboratory and disease characteristics on PK parameters was assessed. Exposure-response analyses explored relationships between amatuximab exposure and overall survival (OS), progression-free survival (PFS) and safety. Alternative amatuximab dosing regimens were explored with simulations using population PK and parametric survival models. RESULTS: Amatuximab PK was best described by a two-compartment model with parallel linear and nonlinear elimination pathways. Body weight and an antidrug antibodies reaction with the titer >64 affected volume of distribution and clearance, respectively. Exposure-response analyses demonstrated that the amatuximab exposure (C min) showed a significant effect on OS (log-rank test, P = 0.0202). For patients with amatuximab C min above the median (38.2 MUg/mL), the median OS was 583 days (90 % CI 418 -NE). For patients with C min <= 38.2 MUg/mL, the median OS was 375 days (90 % CI 325-486). The amatuximab exposure showed similar significant effect on PFS. Exposure-response analysis for adverse events did not reveal any relationship. CONCLUSIONS: In patients with MPM, higher amatuximab exposure in combination with chemotherapy was shown to be associated with longer OS, supporting evaluation of more frequent dosing in future trials to achieve higher exposure and subsequently longer OS. PMID- 26898300 TI - Population pharmacokinetics of sonidegib (LDE225), an oral inhibitor of hedgehog pathway signaling, in healthy subjects and in patients with advanced solid tumors. AB - PURPOSE: Sonidegib (Odomzo) selectively inhibits smoothened and suppresses the growth of hedgehog pathway-dependent tumors. A population pharmacokinetic (PK) analysis of sonidegib in healthy subjects and patients with advanced solid tumors was conducted to characterize PK, determine variability, and estimate covariate effects. METHODS: PK data from five phase 1 or 2 studies (N = 436) in the dose range from 100 to 3000 mg were analyzed using NONMEM. A two-compartment base model with first-order absorption, lag time, linear elimination, and bioavailability that decreased with dose was updated to describe the PK of sonidegib. Covariate analyses were performed and were incorporated into the population PK full model. RESULTS: The base and full models were robust with a good fit to the study data. Population-predicted geometric means (inter individual variability, CV%) of apparent oral clearance, apparent volume of distribution at steady state, accumulation ratio, and elimination half-life were 9.5 L/h (71.4 %), 9163 L (74.9 %), 21 (131 %) and 29.6 days (109 %). Clinically relevant covariate effects were: A high-fat meal increased sonidegib bioavailability fivefold, healthy volunteers had threefold higher clearance, sonidegib bioavailability decreased with increasing dose levels, and PPI coadministration reduced sonidegib bioavailability by 30 %. Sonidegib PK was not significantly impacted by baseline age, weight, total bilirubin, alanine aminotransferase, albumin, creatinine clearance, gender, and ethnicity (Western countries versus Japanese). CONCLUSION: No dose adjustment is needed for mild hepatic impairment, mild and moderate renal impairment, age, weight, gender, or ethnicity. This population PK model adequately characterizes sonidegib PK characteristics and can be used for various simulations and applications. PMID- 26898298 TI - Insular Cortex is Critical for the Perception, Modulation, and Chronification of Pain. AB - An increasing body of neuroimaging and electrophysiological studies of the brain suggest that the insular cortex (IC) integrates multimodal salient information ranging from sensation to cognitive-affective events to create conscious interoception. Especially with regard to pain experience, the IC has been supposed to participate in both sensory-discriminative and affective-motivational aspects of pain. In this review, we discuss the latest data proposing that subregions of the IC are involved in isolated pain networks: the posterior sensory circuit and the anterior emotional network. Due to abundant connections with other brain areas, the IC is likely to serve as an interface where cross modal shaping of pain occurs. In chronic pain, however, this mode of emotional awareness and the modulation of pain are disrupted. We highlight some of the molecular mechanisms underlying the changes of the pain modulation system that contribute to the transition from acute to chronic pain in the IC. PMID- 26898301 TI - The novel EZH2 inhibitor, GSK126, suppresses cell migration and angiogenesis via down-regulating VEGF-A. AB - PURPOSE: To explore the effects and mechanisms of GSK126, a novel inhibitor of histone methyltransferase enhancer of zeste homologue 2, on cancer cell migration. METHODS: Gastric cancer cell line MGC803 and human lung adenocarcinoma cell line A549 were treated with GSK126 at three doses. Transwell and wound healing assays were conducted to detect cell migration. Human umbilical vein endothelial cells tube formation assay and chick embryo chorioallantoic membrane assay were performed to assess the effects of GSK126 on angiogenesis in vitro and in vivo, respectively. The mRNA level of VEGF-A was detected by quantitative PCR, and the protein levels of VEGF-A were detected both by western blot analysis and immunohistochemistry. Epi-fluorescent intensity was obtained by in vivo imaging. RESULTS: GSK126 inhibited cell migration in both MGC803 and A549 in a dose dependent manner, as revealed by transwell and wound healing assays. The effects of GSK 126 were similar to those of gefitinib at the same doses. Moreover, GSK126 at doses of 20 and 50 uM inhibited angiogenesis both in vitro and in vivo. GSK126 reduced both the mRNA and protein expression of VEGF-A in a dose-dependent manner. Finally, in vivo imaging assay revealed that GSK126 at 200 mg/kg significantly inhibited cancer cell migration. CONCLUSIONS: GSK126 inhibits cell migration and angiogenesis in solid tumor cell lines through down-regulation of VEGF-A expression. Thus, it may be considered as a novel anticancer drug candidate for solid tumor. PMID- 26898303 TI - A simple and accurate protocol for absolute polar metabolite quantification in cell cultures using quantitative nuclear magnetic resonance. AB - Absolute analyte quantification by nuclear magnetic resonance (NMR) spectroscopy is rarely pursued in metabolomics, even though this would allow researchers to compare results obtained using different techniques. Here we report on a new protocol that permits, after pH-controlled serum protein removal, the sensitive quantification (limit of detection [LOD] = 5-25 MUM) of hydrophilic nutrients and metabolites in the extracellular medium of cells in cultures. The method does not require the use of databases and uses PULCON (pulse length-based concentration determination) quantitative NMR to obtain results that are significantly more accurate and reproducible than those obtained by CPMG (Carr-Purcell-Meiboom-Gill) sequence or post-processing filtering approaches. Three practical applications of the method highlight its flexibility under different cell culture conditions. We identified and quantified (i) metabolic differences between genetically engineered human cell lines, (ii) alterations in cellular metabolism induced by differentiation of mouse myoblasts into myotubes, and (iii) metabolic changes caused by activation of neurotransmitter receptors in mouse myoblasts. Thus, the new protocol offers an easily implementable, efficient, and versatile tool for the investigation of cellular metabolism and signal transduction. PMID- 26898302 TI - The mineralocorticoid receptor (MR) regulates ENaC but not NCC in mice with random MR deletion. AB - Aldosterone binds to the mineralocorticoid receptor (MR) and increases renal Na(+) reabsorption via up-regulation of the epithelial Na(+) channel (ENaC) and the Na(+)-K(+)-ATPase in the collecting system (CS) and possibly also via the NaCl cotransporter (NCC) in the distal convoluted tubule (DCT). However, whether aldosterone directly regulates NCC via MR or indirectly through systemic alterations remains controversial. We used mice with deletion of MR in ~20 % of renal tubule cells (MR/X mice), in which MR-positive (MR(wt)) and -negative (MR(ko)) cells can be studied side-by-side in the same physiological context. Adult MR/X mice showed similar mRNA and protein levels of renal ion transport proteins to control mice. In MR/X mice, no differences in NCC abundance and phosphorylation was seen between MR(wt) and MR(ko) cells and dietary Na(+) restriction up-regulated NCC to similar extent in both groups of cells. In contrast, MR(ko) cells in the CS did not show any detectable alpha-ENaC abundance or apical targeting of ENaC neither on control diet nor in response to dietary Na(+) restriction. Furthermore, Na(+)-K(+)-ATPase expression was unaffected in MR(ko) cells of the DCT, while it was lost in MR(ko) cells of the CS. In conclusion, MR is crucial for ENaC and Na(+)-K(+)-ATPase regulation in the CS, but is dispensable for NCC and Na(+)-K(+)-ATPase regulation in the DCT. PMID- 26898304 TI - Label-free electrochemical immunosensor based on Nile blue A-reduced graphene oxide nanocomposites for carcinoembryonic antigen detection. AB - In this article, a novel, label-free, and inherent electroactive redox immunosensor for carcinoembryonic antigen (CEA) based on gold nanoparticles (AuNPs) and Nile blue A (NB) hybridized electrochemically reduced graphene oxide (NB-ERGO) is proposed. The composite of NB-graphene oxide (NB-GO) was prepared by pi-pi stacking interaction. Then, chronoamperometry was adopted to simultaneously reduce HAuCl4 and nanocomposites of NB-GO for synthesizing AuNPs/NB-ERGO. The immunosensor was fabricated by capturing CEA antibody (anti-CEA) at this nanocomposite modified electrode. The immunosensor determination was based on the fact that, due to the formation of antigen-antibody immunocomplex, the decreased response currents of NB were directly proportional to the concentrations of CEA. Under optimal conditions, the linear range of the proposed immunosensor was estimated to be from 0.001 to 40 ng ml(-1) and the detection limit was estimated to be 0.00045 ng ml(-1). The proposed immunosensor was used to determine CEA in clinical serum samples with satisfactory results. The proposed method may provide promising potential application in clinical immunoassays with the properties of facile procedure, stability, high sensitivity, and selectivity. PMID- 26898305 TI - A method for measuring binding constants using unpurified in vivo biotinylated ligands. AB - Obtaining accurate kinetics and steady-state binding constants for biomolecular interactions normally requires pure and homogeneous protein preparations. Furthermore, in many cases, one of the ligands must be labeled. Over the past decade, several technologies have been introduced that allow for the measurement of kinetics constants for multiple different interactions in parallel. One such technology is bio-layer interferometry (BLI), which has been used to develop systems that can measure up to 96 biomolecular interactions simultaneously. However, despite the ever-increasing throughput of the tools available for measuring protein-protein interactions, the preparation of pure protein still remains a bottleneck in the process of producing high-quality kinetics data. Here, we show that high-quality binding data can be obtained using soluble lysate fractions containing protein that has been biotinylated in vivo using BirA and then applied to BLI sensors without further purification. Furthermore, we show that BirA ligase does not necessarily need to be co-overexpressed with the protein of interest for biotinylation of the biotin acceptor peptide to occur, suggesting that the activity of endogenous BirA in Escherichia coli is sufficient for producing enough biotinylated protein for a binding experiment. PMID- 26898306 TI - Comparison of gas chromatography-mass spectrometry and gas chromatography combustion-isotope ratio mass spectrometry analysis for in vivo estimates of metabolic fluxes. AB - Gas chromatography-mass spectrometry (GC-MS) was compared with gas chromatography combustion-isotope ratio mass spectrometry (GC-C-IRMS) for measurements of cholesterol (13)C enrichment after infusion of labeled precursor ([(13)C1,2]acetate). Paired results were significantly correlated, although GC-MS was less accurate than GC-C-IRMS for higher enrichments. Nevertheless, only GC-MS was able to provide information on isotopologue distribution, bringing new insights to lipid metabolism. Therefore, we assessed the isotopologue distribution of cholesterol in humans and dogs known to present contrasted cholesterol metabolic pathways. The labeled tracer incorporation was different in both species, highlighting the subsidiarity of GC-MS and GC-C-IRMS to analyze in vivo stable isotope studies. PMID- 26898307 TI - Frequency comb transferred by surface plasmon resonance. AB - Frequency combs, millions of narrow-linewidth optical modes referenced to an atomic clock, have shown remarkable potential in time/frequency metrology, atomic/molecular spectroscopy and precision LIDARs. Applications have extended to coherent nonlinear Raman spectroscopy of molecules and quantum metrology for entangled atomic qubits. Frequency combs will create novel possibilities in nano photonics and plasmonics; however, its interrelation with surface plasmons is unexplored despite the important role that plasmonics plays in nonlinear spectroscopy and quantum optics through the manipulation of light on a subwavelength scale. Here, we demonstrate that a frequency comb can be transformed to a plasmonic comb in plasmonic nanostructures and reverted to the original frequency comb without noticeable degradation of <6.51 * 10(-19) in absolute position, 2.92 * 10(-19) in stability and 1 Hz in linewidth. The results indicate that the superior performance of a well-defined frequency comb can be applied to nanoplasmonic spectroscopy, quantum metrology and subwavelength photonic circuits. PMID- 26898308 TI - Top-down approach to the superior mesenteric artery and the mesopancreas during pancreatoduodenectomy for pancreatic cancer. AB - Complete surgical resection with microscopically tumor-free resection margins (R0) is the most important survival determinant for patients with localized pancreatic cancer. The medial and posterior resection margins are the dominant sites of microscopic tumor involvement, and outline the so-called mesopancreas. In this study, we present a modified surgical approach to the superior mesenteric artery, celiac trunc, and mesopancreas during pancreatoduodenectomy, which enables a comfortable exposure and radical en bloc clearance of the mesopancreas and the tissue adjacent to the superior mesenteric artery. The dissection of the mesopancreas is directed from the ventral aspect of the portal vein downward along the superior mesenteric artery and the celiac trunc, before the transection of the duodenal mesentery is accomplished. The described technique complements the established surgical approaches to pancreatic head tumors, and is indicated in the absence of portal vein infiltration. J. Surg. Oncol. 2016;113:668-671. (c) 2016 Wiley Periodicals, Inc. PMID- 26898309 TI - Emerging Immunotargets and Immunotherapies in Prostate Cancer. AB - Innate and adaptive immunity are both involved in prostate cancer (PCa) carcinogenesis and progression. On this scenario, several immunotherapeutic approaches have been proposed and are presently under extensive investigation in PCa patients. Among emerging immune targets, immune checkpoint inhibitors such as anti-cytotoxic T-lymphocyteassociated protein 4 (CTLA-4), anti-Programmed death-1 (PD-1) and anti-Programmed death-ligand-1 (PD-L1) agents seem to represent the most promising candidate for these patients, together with oncolytic viruses and vaccines, used alone or in combined strategies. In this review, we focused on emerging immunotherapeutic approaches in patients with PCa, showing the rational for their association with current standard therapies including anti-androgen agents, chemo- or radiation therapy. PMID- 26898310 TI - The Role of the Oxysterol/EBI2 Pathway in the Immune and Central Nervous Systems. AB - Oxysterols are pleiotropic messengers interacting with multiple receptor systems. One of the cognate receptors for oxysterols is EBI2, a G protein-coupled receptor highly expressed in the cells of the immune system. Here we discuss the receptor's role in the adapted immunity and inflammation as well as the receptor's expression and function in the CNS with the focus on astrocytes. We also discuss expression and signalling of oxysterol-producing enzymes such as CH25H and CYP7B1 in the CNS and the immune system. These steps will help to elucidate a possible role for this pathway in the physiology of the central and peripheral nervous system and its possible link to human disease. PMID- 26898311 TI - Combination of worm antigen and proinsulin prevents type 1 diabetes in NOD mice after the onset of insulitis. AB - Animal studies demonstrated that administration of helminth products can protect from autoimmune diseases. However, the success of such administrations is limited in the case of type 1 diabetes, as protection is only provided if the administration is started before the development of insulitis. In this study we investigated whether inclusion of helminth antigen administrations to an antigen specific treatment with proinsulin improves the protective effect by triggering non-specific regulatory immune responses. Using a combination therapy of intraperitoneal Litomosoides sigmodontis antigen and intranasal pro-insulin, onset of diabetes was prevented in NOD mice after insulitis started, while either administration alone failed to protect. This protection was associated with an increased frequency of regulatory T cells within the pancreatic lymph nodes and a reduced inflammation of the pancreatic islets. This suggests that inclusion of helminth antigens improve the protective effect provided by antigen-specific therapies and represent a new potential therapeutic approach against autoimmune diseases. PMID- 26898312 TI - Molecular epidemiology of coxsackievirus B3 infection in Spain, 2004-2014. AB - Epidemiological and clinical characteristics of coxsackievirus B3 infections in Spain were investigated. This enterovirus (EV) type was detected mainly in young children (<6 months) and was associated with neurological (78 %) and respiratory diseases (10 %) but also with myo/pericarditis (10 %). Two myocarditis cases were fatal. Phylogenetic analysis of the VP1 region showed that genotype III circulated in the country between 2004 and 2008 and was replaced by genotype V in 2010. Furthermore, phylogenetic analysis of the 3D region indicated that recombination events have occurred and contributed to the genetic evolution of this EV type. PMID- 26898313 TI - Force fluctuations while pressing and moving against high- and low-friction touch screen surfaces. AB - The purpose of this study was to identify the influence of a high- and low friction surface on the ability to maintain a steady downward force during an index finger pressing and moving task. Fifteen right-handed subjects (24-48 years) performed a static force pressing task and a hybrid pressing and moving task on the surface of an iPad mini while holding a steady 2-N force on high- and low-friction surfaces. Variability of force was quantified as the standard deviation (SD) of normal force (F z) and shear force (F xy) across friction conditions and tasks. The SD of F z was 227 % greater during the hybrid task as compared to the static task (p < .001) and was 19 % greater for the high- versus low-friction condition (p = .033). There were positive correlations between SD of F z and F xy during the hybrid force/motion tasks on the high- and low-friction conditions (r (2) = 0.5 and 0.86, respectively), suggesting significant associations between normal and shear forces for this hybrid task. The correlation between the SD of F z for static and hybrid tasks was r (2) = 0.44, indicating that the common practice of examining the control of static tasks may not sufficiently explain performance during hybrid tasks, at least for the young subjects tested in the current study. As activities of daily living frequently require hybrid force/motion tasks (e.g., writing, doing the dishes, and cleaning counters), the results of this study emphasize the need to study motor performance during hybrid tasks in addition to static force tasks. PMID- 26898314 TI - Coordination of muscles to control the footpath during over-ground walking in neurologically intact individuals and stroke survivors. AB - The central nervous system (CNS) is believed to use the abundant degrees of freedom of muscles and joints to stabilize a particular task variable important for task success, such as footpath during walking. Stroke survivors often demonstrate impaired balance and high incidences of falls due to increased footpath variability during walking. In the current study, we use the uncontrolled manifold (UCM) approach to investigate the role of motor abundance in stabilizing footpath during swing phase in healthy individuals and stroke survivors. Twelve stroke survivors and their age- and gender-matched controls walked over-ground at self-selected speed, while electromyographic and kinematic data were collected. UCM analysis partitioned the variance of muscle groups (modes) across gait cycles into "good variance" (i.e., muscle mode variance leading to a consistent or stable footpath) or "bad variance" (i.e., muscle mode variance resulting in an inconsistent footpath). Both groups had a significantly greater "good" than "bad" variance, suggesting that footpath is an important task variable stabilized by the CNS during walking. The relative variance difference that reflects normalized difference between "good" and "bad" variance was not significantly different between groups. However, significant differences in muscle mode structure and muscle mode activation timing were observed between the two groups. Our results suggest that though the mode structure and activation timing are altered, stroke survivors may retain their ability to explore the redundancy within the neuromotor system and utilize it to stabilize the footpath. PMID- 26898315 TI - Quantitative assessment of the stent/scaffold strut embedment analysis by optical coherence tomography. AB - The degree of stent/scaffold embedment could be a surrogate parameter of the vessel wall-stent/scaffold interaction and could have biological implications in the vascular response. We have developed a new specific software for the quantitative evaluation of embedment of struts by optical coherence tomography (OCT). In the present study, we described the algorithm of the embedment analysis and its reproducibility. The degree of embedment was evaluated as the ratio of the embedded part versus the whole strut height and subdivided into quartiles. The agreement and the inter- and intra-observer reproducibility were evaluated using the kappa and the interclass correlation coefficient (ICC). A total of 4 pullbacks of OCT images in 4 randomly selected coronary lesions with 3.0 * 18 mm devices [2 lesions with Absorb BVS and 2 lesions with XIENCE (both from Abbott Vascular, Santa Clara, CA, USA)] from Absorb Japan trial were evaluated by two investigators with QCU-CMS software version 4.69 (Leiden University Medical Center, Leiden, The Netherlands). Finally, 1481 polymeric struts in 174 cross sections and 1415 metallic struts in 161 cross-sections were analyzed. Inter- and intra-observer reproducibility of quantitative measurements of embedment ratio and categorical assessment of embedment in Absorb BVS and XIENCE had excellent agreement with ICC ranging from 0.958 to 0.999 and kappa ranging from 0.850 to 0.980. The newly developed embedment software showed excellent reproducibility. Computer-assisted embedment analysis could be a feasible tool to assess the strut penetration into the vessel wall that could be a surrogate of acute injury caused by implantation of devices. PMID- 26898317 TI - Reduced sensitivity to context in language comprehension: A characteristic of Autism Spectrum Disorders or of poor structural language ability? AB - We present two experiments examining the universality and uniqueness of reduced context sensitivity in language processing in Autism Spectrum Disorders (ASD), as proposed by the Weak Central Coherence account (Happe & Frith, 2006, Journal of Autism and Developmental Disorders, 36(1), 25). That is, do all children with ASD exhibit decreased context sensitivity, and is this characteristic specific to ASD versus other neurodevelopmental conditions? Experiment 1, conducted in English, was a comparison of children with ASD with normal language and their typically developing peers on a picture selection task where interpretation of sentential context was required to identify homonyms. Contrary to the predictions of Weak Central Coherence, the ASD-normal language group exhibited no difficulty on this task. Experiment 2, conducted in German, compared children with ASD with variable language abilities, typically-developing children, and a second control group of children with Language Impairment (LI) on a sentence completion task where a context sentence had to be considered to produce the continuation of an ambiguous sentence fragment. Both ASD-variable language and LI groups exhibited reduced context sensitivity and did not differ from each other. Finally, to directly test which factors contribute to reduced context sensitivity, we conducted a regression analysis for each experiment, entering nonverbal IQ, structural language ability, and autism diagnosis as predictors. For both experiments structural language ability emerged as the only significant predictor. These convergent findings demonstrate that reduced sensitivity to context in language processing is linked to low structural language rather than ASD diagnosis. PMID- 26898316 TI - Cross-Reactivity among Beta-Lactams. AB - Penicillins and cephalosporins are the major classes of beta-lactam (BL) antibiotics in use today and one of the most frequent causes of hypersensitivity reactions to drugs. Monobactams, carbapenems, oxacephems, and beta-lactamase inhibitors constitute the four minor classes of BLs. This review takes into account mainly the prospective studies which evaluated cross-reactivity among BLs in subjects with a well-demonstrated hypersensitivity to a certain class of BLs by performing allergy tests with alternative BLs and, in case of negative results, administering them. In subjects with either IgE-mediated or T-cell mediated hypersensitivity, cross-reactivity among BLs, particularly among penicillins and among cephalosporins, as well as between penicillins and cephalosporins, seems to be mainly related to structural similarities among their side-chain determinants. Specifically, in penicillin-allergic subjects, cross reactivity between penicillins and cephalosporins may exceed 30% when they are administered cephalosporins with identical side chains to those of responsible penicillins. In these subjects, a few prospective studies have demonstrated a rate of cross-reactivity between penicillins and both carbapenems and aztreonam lower than 1%. With regard to subjects with an IgE-mediated hypersensitivity to cephalosporins, in a single study, about 25% of the 98 subjects with such hypersensitivity had positive results to penicillins, 3% to aztreonam, 2% to imipenem/cilastatin, and 1% to meropenem. The cross-reactivity related to the selective recognition of the BL ring by IgE or T lymphocytes, which entails positive responses to all BLs tested, appears to be exceptional. Some studies concerning cross-reactivity among BLs have found patterns of allergy-test positivity which cannot be explained by either the common BL ring or by similar or identical side chains, thus indicating the possibility of coexisting sensitivities to different BLs because of prior exposures to them. PMID- 26898319 TI - The relationship between weight stigma and eating behavior is explained by weight bias internalization and psychological distress. AB - Weight stigma is associated with a range of negative outcomes, including disordered eating, but the psychological mechanisms underlying these associations are not well understood. The present study tested whether the association between weight stigma experiences and disordered eating behaviors (emotional eating, uncontrolled eating, and loss-of-control eating) are mediated by weight bias internalization and psychological distress. Six-hundred and thirty-four undergraduate university students completed an online survey assessing weight stigma, weight bias internalization, psychological distress, disordered eating, along with demographic characteristics (i.e., age, gender, weight status). Statistical analyses found that weight stigma was significantly associated with all measures of disordered eating, and with weight bias internalization and psychological distress. In regression and mediation analyses accounting for age, gender and weight status, weight bias internalization and psychological distress mediated the relationship between weight stigma and disordered eating behavior. Thus, weight bias internalization and psychological distress appear to be important factors underpinning the relationship between weight stigma and disordered eating behaviors, and could be targets for interventions, such as, psychological acceptance and mindfulness therapy, which have been shown to reduce the impact of weight stigma. The evidence for the health consequences resulting from weight stigma is becoming clear. It is important that health and social policy makers are informed of this literature and encouraged develop anti-weight stigma policies for school, work, and medical settings. PMID- 26898321 TI - Interceptive Orthodontics: A Practical Guide to Occlusal Management. PMID- 26898318 TI - Improvement of pyrazolo[3,4-d]pyrimidines pharmacokinetic properties: nanosystem approaches for drug delivery. AB - Pyrazolo[3,4-d]pyrimidines are a class of compounds with a good activity against several cancer cell lines. Despite the promising anticancer activity, these molecules showed a poor aqueous solubility. This issue could threat the future development of pyrazolo[3,4-d]pyrimidines as clinical drug candidates. With the aim of improving their solubility profile and consequently their pharmacokinetic properties, we have chosen four compounds (1-4) on the base of their anti neuroblastoma activity and we have developed albumin nanoparticles and liposomes for the selected candidates. Albumin nanoparticles and liposomes were prepared and characterized regarding size and zeta-potential distribution, polidispersity index, entrapment efficiency and activity against SH-SY5Y human neuroblastoma cell line. The most promising nanosystem, namely LP-2, was chosen to perform further studies: confocal microscopy, stability and drug release in physiological conditions, and biodistribution. Altogether, the obtained data strongly indicate that the encapsulation of pyrazolo[3,4-d]pyrimidines in liposomes represent an effective method to overcome the poor water solubility. PMID- 26898320 TI - Associations of reward sensitivity with food consumption, activity pattern, and BMI in children. AB - In the current study, the associations of reward sensitivity with weight related behaviors and body mass index were investigated in a general population sample of 443 Flemish children (50.3% boys) aged 5.5-12 years. Cross-sectional data on palatable food consumption frequency, screen time, physical activity, parental education level and measured length and weight were collected. The Drive subscale of the 'Behavioral Inhibition Scale/Behavioral Activation Scale' was used as a short method to measure reward sensitivity. A significant positive association of reward sensitivity with the fast food and sweet drink consumption frequency was found. Furthermore, a significant positive association of reward sensitivity with the z-score of body mass index was demonstrated, which explained additional variance to the variance explained by palatable food consumption frequency, screen time, physical activity and parental education level. Hence, the assessment of reward sensitivity may have an added value to the assessment of weight-related behavior indicators when evaluating the determinants of overweight in a child. In sum, children high in reward sensitivity might be more attracted to fast food and sweet drinks, and hence, might be more vulnerable to develop unfavorable food habits and overweight. These findings suggest that considering inter-individual differences in reward sensitivity is of importance in future childhood obesity prevention campaigns. PMID- 26898322 TI - Comorbidity between neurological illness and psychiatric disorders. AB - Psychiatric disorders are common in many neurological disorders, including epilepsy, migraine, Alzheimer's disease, Parkinson's disease, essential tremor, and stroke. These comorbidities increase disease burden and may complicate the treatment of the combined disorders. Initial studies of the comorbidity of psychiatric and neurological disorders were cross-sectional, and time order of the associations was impossible to elucidate. More recent work has clarified time associations between psychiatric disorders and neurological disorders, particularly in epilepsy and stroke where epidemiological evidence suggests that there is a bidirectional relationship. This article takes an epidemiological approach to understanding these relationships and focuses mostly on epilepsy. Although, these relationships are understood in many neurological disorders, routine screening for psychiatric disorders in neurological disorders is infrequent, mostly due to the lack of partnerships between psychiatrists and neurologists and the paucity of neuropsychiatrists. Much more needs to be done to improve the detection and treatment of patients affected by neurological and psychiatric disorders. Understanding the scope of this overlap may inspire collaborations to improve the lives of people affected by both disorders. PMID- 26898323 TI - Distal-less homeobox genes of insects and spiders: genomic organization, function, regulation and evolution. AB - The Distal-less (Dll) genes are homeodomain transcription factors that are present in most Metazoa and in representatives of all investigated arthropod groups. In Drosophila, the best studied insect, Dll plays an essential role in forming the proximodistal axis of the legs, antennae and analia, and in specifying antennal identity. The initiation of Dll expression in clusters of cells in mid-lateral regions of the Drosophila embryo represents the earliest genetic marker of limbs. Dll genes are involved in the development of the peripheral nervous system and sensitive organs, and they also function as master regulators of black pigmentation in some insect lineages. Here we analyze the complete genomes of six insects, the nematode Caenorhabditis elegans and Homo sapiens, as well as multiple Dll sequences available in databases in order to examine the structure and protein features of these genes. We also review the function, expression, regulation and evolution of arthropod Dll genes with emphasis on insects and spiders. PMID- 26898324 TI - Circulating miR-210 as a diagnostic and prognostic biomarker for colorectal cancer. AB - microRNA-210 (miR-210), the master hypoxamir, is overexpressed and generally exhibits oncogenic properties in most human solid tumours, including colorectal cancer (CRC). However, the status of circulating miR-210 in CRC is still unknown. This study aims to assess the clinical significance of circulating miR-210 in CRC. Using (reverse transcription quantitative PCR) RT-qPCR analysis, we compared the expression levels of circulating miR-210 in serum of 268 CRC patients and 102 healthy controls, and found that serum miR-210 was significantly higher in CRC than in healthy controls (P < 0.001). The area under the receiver operating characteristic curve (AUC) of circulating miR-210 to detect CRC was 0.821, with a sensitivity of 74.6% and a specificity of 73.5%. The AUC of circulating miR-210 showed significantly higher detection capability than that of carcinoembryogenic antigen (P < 0.05). Kaplan-Meier analysis demonstrated that increased serum miR 210 level correlated with reduced overall survival (OS) and disease-free survival (DFS) (P = 0.008 and P = 0.008 respectively). Cox analysis indicated circulating miR-210 was an independent prognostic factor for OS and DFS. Taken together, our data suggested that circulating miR-210 could be a potential non-invasive marker for diagnosis and prognosis of CRC. PMID- 26898326 TI - Sex and age specific effects of delta-9-tetrahydrocannabinol during the periadolescent period in the rat: The unique susceptibility of the prepubescent animal. AB - Adolescents who use marijuana are more likely to exhibit anxiety, depression, and other mood disorders, including psychotic-like symptoms. Additionally, the age at onset of use and the stress history of the individual can affect responses to cannabis. To examine the effect of early life experience on adolescent Delta-9 tetrahydrocannabinol (THC) exposure, we exposed adolescent (postnatal day (P) 29 38) male and female rats, either shipped from a supplier or born in our vivarium, to once daily injections of 3mg/kg THC. Our findings suggest that males are more sensitive to the anxiolytic and antidepressant effects of THC, as measured by the elevated plus maze (EPM) and forced swim test (FST), respectively, than females. Exposure to the FST increased plasma corticosterone levels, regardless of drug treatment or origin and females had higher levels than males overall. Shipping increased THC responses in females (acoustic startle habituation) and in males (latency to immobility in FST). No significant effects of THC or shipping on pre pulse inhibition were observed. Due to differences in timing of puberty in males and females during the P29-38 period of THC treatment, we also dosed female rats between P21-30 (pre-puberty) and male rats between P39-48 (puberty). Pre-pubertal animals showed reductions in anxiety on the EPM, an effect that was not seen in animals treated during puberty. These results suggest that both sexes are more susceptible to changes in emotional behavior when THC exposure occurs just prior to the onset of puberty. Within the animals dosed from P29-38, THC increased cannabinoid receptor 1 (CB1R) mRNA expression and tended to decrease CP55,940 stimulated [35S]GTPgammaS binding in the central amygdala only of females. Therefore, early stress enhances THC responses in males (in FST) and females (ASR habituation), THC alters CB1R expression and function in females only and prepubescent rats are generally more responsive to THC than pubertal rats. In summary, THC and stress interact with the developing endocannabinoid system in a sex specific manner during the peri-pubertal period. PMID- 26898325 TI - Large Cell Neuroendocrine Carcinoma of the Lung: Clinico-Pathologic Features, Treatment, and Outcomes. AB - BACKGROUND: Large cell neuroendocrine carcinoma (LCNEC) accounts for approximately 3% of lung cancers. Pathologic classification and optimal therapies are debated. We report the clinicopathologic features, treatment and survival of a series of patients with stage IV LCNEC. MATERIALS AND METHODS: Cases of pathologically-confirmed stage IV LCNEC evaluated at Memorial Sloan Kettering Cancer Center from 2006 to 2013 were identified. We collected demographic, treatment, and survival data. Available radiology was evaluated by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria. RESULTS: Forty-nine patients with stage IV LCNEC were identified. The median age was 64 years, 63% of patients were male, and 88% were smokers. Twenty-three patients (n = 23/49; 47%) had brain metastases, 17 at diagnosis and 6 during the disease course. Seventeen LCNEC patients (35%) had molecular testing, of which 24% had KRAS mutations (n = 4/17). Treatment data for first-line metastatic disease was available on 37 patients: 70% (n = 26) received platinum/etoposide and 30% (n = 11) received other regimens. RECIST was completed on 23 patients with available imaging; objective response rate was 37% (95% confidence interval, 16%-62%) with platinum/etoposide, while those treated with other first-line regimens did not achieve a response. Median overall survival was 10.2 months (95% confidence interval, 8.6-16.4 months) for the entire cohort. CONCLUSION: Patients with stage IV LCNEC have a high incidence of brain metastases. KRAS mutations are common. Patients with stage IV LCNEC do not respond as well to platinum/etoposide compared with historic data for extensive stage small-cell lung cancer; however, the prognosis is similar. Prospective studies are needed to define optimum therapy for stage IV LCNEC. PMID- 26898328 TI - Type II PKAs are anchored to mature insulin secretory granules in INS-1 beta cells and required for cAMP-dependent potentiation of exocytosis. AB - Specificity of the cAMP-dependent protein kinase (PKA) pathway relies on an extremely sophisticated compartmentalization mechanism of the kinase within a given cell, based on high-affinity binding of PKA tetramer pools to different A Kinase Anchoring Proteins (AKAPs). We and others have previously shown that AKAPs dependent PKA subcellular targeting is a requisite for optimal cAMP-dependent potentiation of insulin exocytosis. We thus hypothesized that a PKA pool may directly anchor to the secretory compartment to potentiate insulin exocytosis. Here, using immunofluorescence analyses combined to subcellular fractionations and purification of insulin secretory granules (ISGs), we identified discrete subpools of type II PKAs, RIIalpha and RIIbeta PKAs, along with the catalytic subunit, physically associated with ISGs within pancreatic insulin-secreting beta cells. Ultrastructural analysis of native rodent beta-cells confirmed in vivo the occurrence of PKA on dense-core ISGs. Isoform-selective disruption of binding of PKAs to AKAPs reinforced the requirement of type II PKA isoforms for cAMP potentiation of insulin exocytosis. This granular localization of PKA was of critical importance since siRNA-mediated depletion of either RIIalpha or RIIbeta PKAs resulted in a significant reduction of cAMP-dependent potentiation of insulin release. The present work provides evidence for a previously unrecognized pool of type II PKAs physically anchored to the beta-cell ISGs compartment and supports a non-redundant function for type II PKAs during cAMP potentiation of exocytosis. PMID- 26898327 TI - Distinct effects of ketamine and acetyl L-carnitine on the dopamine system in zebrafish. AB - Ketamine, a noncompetitive N-methyl-D-aspartic acid (NMDA) receptor antagonist is commonly used as a pediatric anesthetic. We have previously shown that acetyl L carnitine (ALCAR) prevents ketamine toxicity in zebrafish embryos. In mammals, ketamine is known to modulate the dopaminergic system. NMDA receptor antagonists are considered as promising anti-depressants, but the exact mechanism of their function is unclear. Here, we measured the levels of dopamine (DA) and its metabolites, 3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in the zebrafish embryos exposed to ketamine in the presence and absence of 0.5 mM ALCAR. Ketamine, at lower doses (0.1-0.3 mM), did not produce significant changes in DA, DOPAC or HVA levels in 52 h post-fertilization embryos treated for 24 h. In these embryos, tyrosine hydroxylase (TH) mRNA expression remained unchanged. However, 2 mM ketamine (internal embryo exposure levels equivalent to human anesthetic plasma concentration) significantly reduced DA level and TH mRNA indicating that DA synthesis was adversely affected. In the presence or absence of 2 mM ketamine, ALCAR showed similar effects on DA level and TH mRNA, but increased DOPAC level compared to control. ALCAR reversed 2 mM ketamine-induced reduction in HVA levels. With ALCAR alone, the expression of genes encoding the DA metabolizing enzymes, MAO (monoamine oxidase) and catechol-O-methyltransferase (COMT), was not affected. However, ketamine altered MAO mRNA expression, except at the 0.1 mM dose. COMT transcripts were reduced in the 2 mM ketamine-treated group. These distinct effects of ketamine and ALCAR on the DA system may shed some light on the mechanism on how ketamine can work as an anti-depressant, especially at sub-anesthetic doses that do not affect DA metabolism and suppress MAO gene expression. PMID- 26898332 TI - Sacrificial conversion of layered rare-earth hydroxide (LRH) nanosheets into (Y1 xEux)PO4 nanophosphors and investigation of photoluminescence. AB - Ultra-thin nanosheets (2-6 nm) of the (Y1-xEux)2(OH)5NO3.nH2O layered rare-earth hydroxide (LRH), directly crystallized without exfoliation were employed for the first time as a sacrificial precursor to synthesize (Y1-xEux)PO4 orthophosphate red phosphors via nano-conversion, and anion exchange of both the hydroxyls and NO3(-) in the LRH with the phosphate ions from diammonium hydrogen phosphate ((NH4)2HPO4) is discussed. Detailed characterization of the materials was performed by the combined techniques of XRD, FTIR, TG/DSC, FE-SEM, HR-TEM, and photoluminescence spectroscopy. The (Y1-xEux)PO4 phosphors, with crystallite sizes of up to ~20 nm, were found to exhibit stronger (5)D0 -> (7)F2 (621 nm) than (5)D0 -> (7)F1 (595 nm) emissions under charge transfer excitation (236 nm) owing to the nano-size effect. The optimal Eu(3+) content was determined to be ~10 at% (x = 0.10), and concentration quenching of luminescence was analyzed to result from exchange interactions. The effects of the Eu(3+) content and annealing temperature on the structural features and luminescence properties of the (Y1-xEux)PO4 nanophosphors were discussed in detail, including emission intensity, the asymmetry factor of luminescence, fluorescence lifetime, and CIE chromaticity coordinates. PMID- 26898329 TI - Sialylated Milk Oligosaccharides Promote Microbiota-Dependent Growth in Models of Infant Undernutrition. AB - Identifying interventions that more effectively promote healthy growth of children with undernutrition is a pressing global health goal. Analysis of human milk oligosaccharides (HMOs) from 6-month-postpartum mothers in two Malawian birth cohorts revealed that sialylated HMOs are significantly less abundant in those with severely stunted infants. To explore this association, we colonized young germ-free mice with a consortium of bacterial strains cultured from the fecal microbiota of a 6-month-old stunted Malawian infant and fed recipient animals a prototypic Malawian diet with or without purified sialylated bovine milk oligosaccharides (S-BMO). S-BMO produced a microbiota-dependent augmentation of lean body mass gain, changed bone morphology, and altered liver, muscle, and brain metabolism in ways indicative of a greater ability to utilize nutrients for anabolism. These effects were also documented in gnotobiotic piglets using the same consortium and Malawian diet. These preclinical models indicate a causal, microbiota-dependent relationship between S-BMO and growth promotion. PMID- 26898330 TI - Axon Degeneration Gated by Retrograde Activation of Somatic Pro-apoptotic Signaling. AB - During development, sensory axons compete for limiting neurotrophic support, and local neurotrophin insufficiency triggers caspase-dependent axon degeneration. The signaling driving axon degeneration upon local deprivation is proposed to reside within axons. Our results instead support a model in which, despite the apoptotic machinery being present in axons, the cell body is an active participant in gating axonal caspase activation and axon degeneration. Loss of trophic support in axons initiates retrograde activation of a somatic pro apoptotic pathway, which, in turn, is required for distal axon degeneration via an anterograde pro-degenerative factor. At a molecular level, the cell body is the convergence point of two signaling pathways whose integrated action drives upregulation of pro-apoptotic Puma, which, unexpectedly, is confined to the cell body. Puma then overcomes inhibition by pro-survival Bcl-xL and Bcl-w and initiates the anterograde pro-degenerative program, highlighting the role of the cell body as an arbiter of large-scale axon removal. PMID- 26898333 TI - Fabrication and optical enhancing properties of discrete supercrystals. AB - Discrete gold nanoparticle crystals with tunable size and morphology are fabricated via a fast and inexpensive template-assisted method. The highly precise hierarchical organization of the plasmonic building blocks yields superstructures with outstanding behaviour for surface-enhanced Raman scattering analysis. PMID- 26898331 TI - TGF-beta Tumor Suppression through a Lethal EMT. AB - TGF-beta signaling can be pro-tumorigenic or tumor suppressive. We investigated this duality in pancreatic ductal adenocarcinoma (PDA), which, with other gastrointestinal cancers, exhibits frequent inactivation of the TGF-beta mediator Smad4. We show that TGF-beta induces an epithelial-mesenchymal transition (EMT), generally considered a pro-tumorigenic event. However, in TGF-beta-sensitive PDA cells, EMT becomes lethal by converting TGF-beta-induced Sox4 from an enforcer of tumorigenesis into a promoter of apoptosis. This is the result of an EMT-linked remodeling of the cellular transcription factor landscape, including the repression of the gastrointestinal lineage-master regulator Klf5. Klf5 cooperates with Sox4 in oncogenesis and prevents Sox4-induced apoptosis. Smad4 is required for EMT but dispensable for Sox4 induction by TGF-beta. TGF-beta-induced Sox4 is thus geared to bolster progenitor identity, whereas simultaneous Smad4-dependent EMT strips Sox4 of an essential partner in oncogenesis. Our work demonstrates that TGF-beta tumor suppression functions through an EMT-mediated disruption of a lineage-specific transcriptional network. PMID- 26898334 TI - Design and synthesis of [(125)I]Pyricoxib: A novel (125)I-labeled cyclooxygenase 2 (COX-2) inhibitors. AB - Cyclooxygenase-2 (COX-2) is the key enzyme in the prostaglandin synthesis pathway which is involved in various pathophysiological conditions. The enzyme is membrane bound and located inside of the endoplasmic reticulum and nuclear membrane. Effective perfusion of inhibitors to the active site requires lipophilic drugs, which consequently display high unspecific background accumulation, for example, in fatty tissues. The objective of this work was the development of a small molecule radiolabeled with a long-lived iodine radioisotope to enable longer imaging times and better target-to-background ratios. A group of iodinated compounds (8-10) was synthesized and identified as selective COX-2 inhibitors (COX-2 IC50=0.85-13 MUM). Molecular docking results provided the theoretical support for the experimental COX-2 inhibition data. Furthermore, a novel (125)I-containing trifluoro-pyrimidine compound ([(125)I]Pyricoxib) was prepared via radioiododestannylation reaction as potent and selective COX-2 inhibitor. Radiosynthesis of [(125)I]Pyricoxib was accomplished with innovative fluorous chemistry using fluorous chloroamine-T (F CAT) as novel oxidizing agent in high radiochemical yields of 91 +/- 4%. PMID- 26898335 TI - Identification of potent and selective MTH1 inhibitors. AB - Structure based design of a novel class of aminopyrimidine MTH1 (MutT homolog 1) inhibitors is described. Optimization led to identification of IACS-4759 (compound 5), a sub-nanomolar inhibitor of MTH1 with excellent cell permeability and good metabolic stability in microsomes. This compound robustly inhibited MTH1 activity in cells and proved to be an excellent tool for interrogation of the utility of MTH1 inhibition in the context of oncology. PMID- 26898336 TI - One-pot synthesis and antimicrobial evaluation of novel 3-cyanopyridine derivatives of (-)-beta-pinene. AB - A series of novel 3-cyanopyridine derivatives of (-)-beta-pinene were designed and synthesized by one-pot four-component domino reactions. The targeted compounds were evaluated for their antimicrobial activity against four bacteria (Klebsiella pneumoniae, Enterobacter aerogenes, Staphylococcus aureus, Staphylococcus epidermidis) and a fungus (Candida albicans). The results showed that most of the minimal inhibitory concentrations (MICs) of these 3 cyanopyridine derivatives against the tested strains was in the range of 15.6-125 mg/L. Among these 3-cyanopyridine derivatives, the MICs of compound 5h against S. epidermidis and C. albicans were 15.6 mg/L, which revealed that compound 5h featured double fluoro substituents at meta- and para-position was the most active compound. In addition, the preliminary structure-activity relationship analysis indicated that the change of substituents on the pyridine ring and benzene ring of 3-cyanopyridine derivatives was an important factor for inducing antimicrobial activity. This research would promote the development of heterocyclic derivatives of beta-pinene with antimicrobial activity. PMID- 26898337 TI - Synthesis and biological evaluation of 2-aroylbenzofurans, rugchalcones A, B and their derivatives as potent anti-inflammatory agents. AB - An efficient synthesis of 2-aroylbenzofurans, rugchalcones A, B and their derivatives was accomplished in excellent yields by the Rap-Stoermer reaction between substituted salicylaldehydes and phenacyl bromides. Later their anti inflammatory effects were evaluated in lipopolysaccharide (LPS)-induced RAW-264.7 macrophages. The compounds were exhibited exceptional potency against inflammatory mediated NO production with no cytotoxicity at 10 MUM concentration and IC50 values are found in the range from 0.75 to 13.27 MUM. Among the 2 aroylbenzofurans prepared in this study, compounds 4 (99.6%; IC50=0.57), rugchalcone B (2) (99.3%; IC50=4.13), 7 (96.8%; IC50=1.90) and 8 (74.3%; IC50=0.99) were showed the maximum inhibitory activity. This study suggests that compounds 2, 4, 7 and 8 which are having 4-hydroxyphenyl group and/or hydroxy ( OH) group at 5- and/or 6-position of benzofuran motif could be considered as a promising scaffolds for the further development of iNOS inhibitors for potential anti-inflammatory applications. PMID- 26898338 TI - Synthesis of pyrimido[4,5-c]azepine- and pyrimido[4,5-c]oxepine-based gamma secretase modulators. AB - This Letter describes an efficient ring-closing metathesis approach to 2-chloro-4 amino-pyrimido[4,5-c]azepines and 2-chloro-4-amino-pyrimido[4,5-c]oxepines. These chlorides were applied to the synthesis of several potent gamma-secretase modulators (GSMs). PMID- 26898339 TI - Cross-cultural adaptation, reliability and validity of the Turkish version of the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire. AB - BACKGROUND: Low back pain is among the most common musculoskeletal system disorders. Outcome measures are needed for the measurement of function, to establish a treatment program, and for monitoring the improvement in low back pain. There exist several questionnaires enquiring about function in low back pain. One of these is Japanese Orthopaedic Association Back Pain Evaluation Questionnaire, whose reliability and validity were previously established. Other than the original version of the questionnaire, only its Persian version exists. The present study aims to investigate the cross-cultural adaptation, reliability and validity of the Turkish version of the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire. METHODS: The study included 103 patients with low back pain. For reliability assessment of the questionnaire, test-retest and internal consistency analyses were performed. The results of test-retest analysis were assessed by Intraclass Correlation Coefficient method. For internal consistency, Cronbach Alpha value was used. Validity analyses of the questionnaire were performed by construct validity. For construct validity, convergent validity was tested. Convergent validity of the questionnaire was calculated via its correlation with suitable subscales of the Short Form-36 and the total score of the Oswestry Disability Index by using Pearson's correlation coefficient. RESULTS: Intraclass Correlation Coefficient values for test-retest reliability were found to be in the range of 0.765-0.924, which indicate a sufficient level of test-retest reliability. Cronbach's Alpha value was found to be 0.804 indicating a high internal consistency. Pearson's correlation coefficient between Japanese Orthopaedic Association Back Pain Evaluation Questionnaire to Short Form-36 and Oswestry Disability Index values were ranged between 0.424 and -0.810, indicating a good correlation. CONCLUSIONS: Considering all these data, it was concluded that the Turkish version of the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire is valid and reliable. PMID- 26898340 TI - Intra-articular implantation of gentamicin impregnated collagen sponge causes joint inflammation and impaired renal function in dogs. AB - OBJECTIVE: Gentamicin impregnated collagen sponge (GICS) can be used to treat intra-articular surgical site infections. High local concentrations of gentamicin can be reached for short periods; however the collagen vehicle may persist for much longer periods. We wished to determine the effect of sponge implantation on joint inflammation and renal function. METHODS: Eighteen medium sized mixed breed research dogs of hound type were randomized to two groups; arthroscopic implantation of GICS at gentamicin dose = 6 mg/kg (n = 9) or sham operation (n = 9). Endpoints consisted of joint inflammation measured by synovial fluid cell counts and cytokine concentrations; lameness measured by force plate asymmetry indices; and renal function measured by glomerular filtration rate (GFR) study. The prevalence of lesions associated with aminoglycoside nephrotoxicity was assessed by renal biopsy and transmission electron microscopy. RESULTS: Gentamicin impregnated collagen sponge implantation caused joint inflammation (p <0.01), lameness (p = 0.04), and decreased GFR (p = 0.04). No difference was observed in the prevalence of renal lesions on biopsy between the treatment and control groups (p = 0.49). CLINICAL SIGNIFICANCE: Gentamicin impregnated collagen sponge implantation causes joint inflammation and lameness as well as GFR reductions at the dose assessed. Gentamicin impregnated collagen sponge are not recommended for intra-articular implantation in dogs. PMID- 26898341 TI - Lysosomal glycosphingolipid catabolism by acid ceramidase: formation of glycosphingoid bases during deficiency of glycosidases. AB - Glycosphingoid bases are elevated in inherited lysosomal storage disorders with deficient activity of glycosphingolipid catabolizing glycosidases. We investigated the molecular basis of the formation of glucosylsphingosine and globotriaosylsphingosine during deficiency of glucocerebrosidase (Gaucher disease) and alpha-galactosidase A (Fabry disease). Independent genetic and pharmacological evidence is presented pointing to an active role of acid ceramidase in both processes through deacylation of lysosomal glycosphingolipids. The potential pathophysiological relevance of elevated glycosphingoid bases generated through this alternative metabolism in patients suffering from lysosomal glycosidase defects is discussed. PMID- 26898343 TI - Determination of Bromine Stable Isotope Ratios from Saline Solutions by "Wet Plasma" MC-ICPMS Including a Comparison between High- and Low-Resolution Modes, and Three Introduction Systems. AB - We describe a novel method for measuring stable bromine isotope compositions in saline solutions such as seawater, brines, and formation waters. Bromine is extracted from the samples by ion exchange chromatography on anion exchange resin AG 1-X4 with NH4NO3 and measured by MC-ICP-MS in wet plasma conditions. Sample introduction through a small spray chamber provided good sensitivity and stability of the Br signal compared to direct injection (d-DIHEN) and desolvation (APEX). NH4NO3 media allowed fast (<3 min) washing of the system. Despite Ar2H(+) spectral interference on (81)Br(+), for the first time low-resolution mode (with appropriate tuning of Ar2H(+)/(81)Br(+) sensitivity) gave higher precision (81)Br/(79)Br measurements than high-resolution (HR), due to the narrowness of the (81)Br(+) plateau in HR mode and to slight mass drifting with time. Additionally, 1 MUg Br is the lower amount needed for a triplicate determination of delta(81)Br by MC-ICP-MS, with reproducibility often < +/- 0.10/00 (2 SD). Four HBr solutions were prepared by evaporation/condensation in order to obtain in-house reference solutions with 30/00 variations in delta(81)Br and to assess the reproducibility and accuracy of the method. Long-term (>3 years) reproducibility between +/- 0.11 and +/- 0.270/00 (2 SD) was obtained for the four HBr solutions, the international standard reference material NIST SRM 977 (delta(81)BrSMOB = -0.65 +/- 1.10/00, 1 SD), and seawaters (synthetic and natural). The accuracy of the MC-ICP-MS method was validated by comparing the delta(81)Br obtained for these solutions with dual-inlet IRMS measurements on CH3Br gas. Finally, the method was successfully applied to 22 natural samples. PMID- 26898342 TI - Mammalian interspecies substitution of immune modulatory alleles by genome editing. AB - We describe a fundamentally novel feat of animal genetic engineering: the precise and efficient substitution of an agronomic haplotype into a domesticated species. Zinc finger nuclease in-embryo editing of the RELA locus generated live born domestic pigs with the warthog RELA orthologue, associated with resilience to African Swine Fever. The ability to efficiently achieve interspecies allele introgression in one generation opens unprecedented opportunities for agriculture and basic research. PMID- 26898344 TI - Induction of site-specific chromosomal translocations in embryonic stem cells by CRISPR/Cas9. AB - Chromosomal translocation is the most common form of chromosomal abnormality and is often associated with congenital genetic disorders, infertility, and cancers. The lack of cellular and animal models for chromosomal translocations, however, has hampered our ability to understand the underlying disease mechanisms and to develop new therapies. Here, we show that site-specific chromosomal translocations can be generated in mouse embryonic stem cells (mESCs) via CRISPR/Cas9. Mouse ESCs carrying translocated chromosomes can be isolated and expanded to establish stable cell lines. Furthermore, chimeric mice can be generated by injecting these mESCs into host blastocysts. The establishment of ESC-based cellular and animal models of chromosomal translocation by CRISPR/Cas9 provides a powerful platform for understanding the effect of chromosomal translocation and for the development of new therapeutic strategies. PMID- 26898345 TI - Global proteomic profiling identifies etoposide chemoresistance markers in non small cell lung carcinoma. AB - Chemoresistance is one of the leading health concerns in cancer treatment. Understanding the mechanism of chemoresistance is the best way to improve the survival of the patient. Etoposide and its analogues are widely used as antitumor drugs in lung cancer but many etoposide resistant lung cancer cases has been identified in recent years. The present study aims to explore the cellular response of lung cancer cell lines to etoposide and finding the potential chemoresistant marker proteins. Multiple proteomic platforms like 2-DE, DIGE and iTRAQ have been used to study the global proteome profile of NCI-H460 and etoposide resistant NCI-H460R cell lines. Our study revealed that etoposide treatment leads to alteration of 83 proteins in NCI-H460R cell lines. The functional analysis highlighted the role of the differential expressed proteins in cellular signaling, apoptosis, and cytoskeleton reorganization. Our study has identified several new proteins like RHOC, DLG5, UGDH, TMOD3 in addition to known chemoresistance associated proteins. In silico prediction of the important selected candidates are further validated at protein and mRNA level. Further, functional studies of newly identified candidate genes RHOC and DLG5 revealed that chemotherapeutic resistance is associated with their elevated level and may serve as novel targets for therapeutic intervention. BIOLOGICAL SIGNIFICANCE: Etoposide and its analogues have been used for lung cancer treatment for a while and it was reported that many non small cell lung carcinoma patients are resistant to etoposide. Although etoposide show drug resistance, the exact mechanism was not well understood. The present study focused on the global proteome analysis of NCI-H460 and NCI-H460R cell lines using multiple proteomic platforms to understand the potential chemoresistant markers for etoposide. Our multi-proteomic analysis has showed differential expression of 83 proteins involved in oxidative phosphorylation, metabolic, protein folding, cytoskeleton associated protein along with apoptotic pathway has been identified. In addition, quite a few interesting proteins such as RHOC, DLG5, HSP90, citrate synthase, UDP glucose-6-dehydrogenase, Tropomodulin-3 are involved in chemoresistance has been observed. Overall, this is the first comprehensive proteomic study on etoposide resistant cell line NCI-H460 to explore the mechanism of chemoresistance in lung cancer. PMID- 26898346 TI - Microfluidic model of the platelet-generating organ: beyond bone marrow biomimetics. AB - We present a new, rapid method for producing blood platelets in vitro from cultured megakaryocytes based on a microfluidic device. This device consists in a wide array of VWF-coated micropillars. Such pillars act as anchors on megakaryocytes, allowing them to remain trapped in the device and subjected to hydrodynamic shear. The combined effect of anchoring and shear induces the elongation of megakaryocytes and finally their rupture into platelets and proplatelets. This process was observed with megakaryocytes from different origins and found to be robust. This original bioreactor design allows to process megakaryocytes at high throughput (millions per hour). Since platelets are produced in such a large amount, their extensive biological characterisation is possible and shows that platelets produced in this bioreactor are functional. PMID- 26898347 TI - Transcriptome-wide targets of alternative splicing by RBM4 and possible role in cancer. AB - This study determined transcriptome-wide targets of the splicing factor RBM4 using Affymetrix GeneChip((r)) Human Exon 1.0 ST Arrays and HeLa cells treated with RBM4-specific siRNA. This revealed 238 transcripts that were targeted for alternative splicing. Cross-linking and immunoprecipitation experiments identified 945 RBM4 targets in mouse HEK293 cells, 39% of which were ascribed to "alternative splicing" by in silico pathway analysis. Mouse embryonic stem cells transfected with Rbm4 siRNA hairpins exhibited reduced colony numbers and size consistent with involvement of RBM4 in cell proliferation. RBM4 cDNA probing of a cancer cDNA array involving 18 different tumor types from 13 different tissues and matching normal tissue found overexpression of RBM4 mRNA (p<0.01) in cervical, breast, lung, colon, ovarian and rectal cancers. Many RBM4 targets we identified have been implicated in these cancers. In conclusion, our findings reveal transcriptome-wide targets of RBM4 and point to potential cancer-related targets and mechanisms that may involve RBM4. PMID- 26898348 TI - Comparison of the clinical effects of combined salmeterol/fluticasone delivered by dry powder or pressurized metered dose inhaler. AB - The salmeterol/fluticasone combination (SFC) inhaler is currently the most widely used maintenance drug for asthmatics worldwide. Although the effectiveness of SFC as either a dry powder inhaler (DPI) or a pressurized metered dose inhaler (pMDI) is well documented, there is limited data comparing the clinical efficacies of the two devices. To address this issue, we carried out a randomized crossover trial in which asthmatic patients (n = 47; mean age, 62.5 +/- 16.5 years old) received a 12-week treatment of SFC DPI (50/250 MUg twice daily) or SFC pMDI (four puffs of 25/125 MUg daily). After a 4-week washout period, patients received another crossover treatment for 12 weeks. Respiratory resistance and reactance were measured by forced oscillation technique (MostGraph-01), spirometry, fractional exhaled nitric oxide (FeNO), and an asthma control test (ACT) every 4 weeks. The mean forced expiratory volume1.0 at the baseline was 2.16 +/- 0.86 (L). Respiratory system resistance at 5 Hz (R5), the difference between R5 and R at 20 Hz (R5 - R20), and FeNO improved in both treatment groups, while reactance at 5 Hz (X5) and ACT score improved only in the pMDI group. In patients >70 years old (n = 21), R5, R5 - R20, DeltaX5, and FeNO improved only in the pMDI group. These results suggest that SFC by pMDI produces a stronger anti inflammatory and bronchodilatory effect even in patients whose asthma is well controlled by SFC delivered by DPI. PMID- 26898349 TI - Investigation of larvae digestive beta-glucosidase and proteases of the tomato pest Tuta absoluta for inhibiting the insect development. AB - The tomato leaf miner Tuta absoluta is one of the most devastating pests for tomato crops. Digestive proteases and beta-glucosidase enzymes were investigated using general and specific substrates and inhibitors. Maximal beta-glucosidase and proteolytic activities occurred at temperature and pH optima of 30 and 40 degrees C, 5 and 10-11 unit of pH, respectively. Zymogram analysis showed the presence of distinguished beta-glucosidase exhibiting a specific activity of about 183 +/- 15 umol min-1 mg-1. In vitro inhibition experiments suggested that serine proteases were the primary gut proteases. Gel based protease inhibition assays demonstrated that the 28 and 73 kDa proteases might be trypsin-like and chymotrypsin-like enzymes, respectively. Overall gut trypsin-like and chymotrypsin-like activities were evaluated to be about 27.2 +/- 0.84 and 1.68 +/ 0.03 umol min-1 mg-1, respectively. Sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis showed that T. absoluta gut serine proteases are responsible for Bacillus thuringiensis Cry insecticidal proteins proteolysis. Additionally, bioassays showed that T. absoluta larvae development was more affected by the beta-glucosidases inhibitor (D-glucono-delta-lactone) than the serine proteases inhibitor (soybean trypsin inhibitor). These results are of basic interest since they present interesting data of beta-glucosidases and gut serine proteases of T. absoluta larvae. PMID- 26898350 TI - Prevalence of mcr-1 in commensal Escherichia coli from French livestock, 2007 to 2014. AB - Colistin resistance was investigated in 1,696 isolates collected from 2007 to 2014 within the frame of the French livestock antimicrobial resistance surveillance programme. The mcr-1 gene was detected in all commensal Escherichia coli isolates with a minimum inhibitory concentration to colistin above the 2 mg/L cut-off value (n=23). In poultry, mcr-1 prevalence was 5.9% in turkeys and 1.8% in broilers in 2014. In pigs, investigated in 2013, this prevalence did not exceed 0.5%. These findings support that mcr-1 has spread in French livestock. PMID- 26898351 TI - Reply to the letter to the editor: Importance of different region-of-interest protocols for the apparent diffusion coefficient measurement of tumors in diffusion-weighted magnetic resonance imaging. PMID- 26898352 TI - That sinking feeling: Suspended sediments can prevent the ascent of coral egg bundles. AB - Spawning synchrony represents a common reproductive strategy in sessile marine organisms and for broadcast spawning corals, buoyancy of egg-sperm bundles is critical to maximise fertilisation at the ocean surface. Here we demonstrate a novel threat to coral reproduction whereby buoyant egg-sperm bundles intercept and are "ballasted" by sediment grains on their journey to the ocean surface, preventing them from reaching the ocean surface and greatly reducing egg-sperm encounter rates. Empirical observations of this mechanism are successfully captured by a mathematical model that predicts the reduction in ascent probability and egg-sperm encounters as a function of sediment load. When applied to 15 m deep reefs, the model predicts that 10% and 50% reductions in egg-sperm encounters occur at 35 mg L(-1) and 87 mg L(-1) suspended sediment concentrations, respectively, and for a 5 m deep reef a 10% reduction occurs at 106 mg L(-1). These concentrations are commonly associated with sediment plumes from dredging or natural resuspension events. The potential for sediments to sink coral gametes highlights the need to carefully manage the timing of turbidity generating human activities near reefs during spawning periods. PMID- 26898353 TI - Intention of dog owners to participate in rabies control measures in Flores Island, Indonesia. AB - The success of a rabies control strategy depends on the commitment and collaboration of dog owners. In this study the theory of planned behaviour (TPB) was used to identify the factors, which are associated with the intention of dog owners to participate in rabies control measures in the Manggarai and Sikka regencies of Flores Island, Indonesia. Questionnaires were administered to 450 dog owners from 44 randomly selected villages in the two regencies. Ninety-six percent of the dog owners intended to participate in a free-of-charge vaccination campaign. The intention decreased to 24% when dog owners were asked to pay a vaccination fee equal to the market price of the vaccine (Rp 18.000 per dose=US$2). Approximately 81% of the dog owners intended to keep their dogs inside their house or to leash them day and night during a period of at least three months in case of an incidence of rabies in the dog population within their village. Only 40% intended to cull their dogs in case of a rabies incident within their village. Using multivariable logistic regression analysis, the attitude item 'vaccinating dogs reduces rabies cases in humans', and the perceived behavioural control items 'availability of time' and 'ability to confine dogs' were shown to be significantly associated with the intention to participate in a free-of-charge vaccination campaign. The attitude item 'culling dogs reduces rabies cases in humans' was significantly associated with the intention to participate in a culling measure. The attitude item 'leashing of dogs reduces human rabies cases' and perceived behavioural controls 'availability of time' and 'money to buy a leash' were associated with the intention to leash dogs during a rabies outbreak. As the attitude variables were often significantly associated with intention to participate in a rabies control measure, an educational rabies campaign focusing on the benefit of rabies control measures is expected to increase the intention of dog owners to participate in future rabies control measures. The significant association between perceived behavioural controls and intention to participate points to other relevant policy interventions. Providing dog owners with a skill to confine dogs and creating a subsidy program for the vaccine and leash costs, by involving non-governmental organisations or charitable organisations, may be useful policy interventions. Moreover appropriate time management, such as implementing vaccination campaigns during the weekend, could increase the intention to participate in vaccination campaigns, by relaxing the constraints on the availability of dog owners' time. PMID- 26898354 TI - Autotetraploid cell line induced by SP600125 from crucian carp and its developmental potentiality. AB - Polyploidy has many advantages over diploidy, such as rapid growth, sterility, and disease resistance, and has been extensively applied in agriculture and aquaculture. Though generation of new polyploids via polyploidization has been achieved in plants by different ways, it is comparatively rare in animals. In this article, by a chemical compound, SP600125, polyploidization is induced in fish cells in vitro, and a stable autotetraploid cell line has been generated from diploid fibroblast cells of crucian carp. As a c-Jun N-terminal kinase (Jnk) inhibitor, SP600125 does not function during the induction process of polyploidization. Instead, the p53 signal pathway might be involved. Using the SP600125-induced tetraploid cells and eggs of crucian carp as the donors and recipients, respectively, nuclear transplantation was conducted such that tetraploid embryos were obtained. It suggests that combining polyploidization and the somatic cell nuclear transfer technique (SCNT) is an efficient way to generate polyploidy, and the presented method in this research for generating the tetraploid fish from diploid fish can provide a useful platform for polyploid breeding. PMID- 26898355 TI - Skin and muscle permeating antibacterial nanoparticles for treating Staphylococcus aureus infected wounds. AB - Majority of the chronic wounds are infected with bacteria like Staphylococcus aureus (S. aureus). The deep tissue infections are difficult to treat using topical antibiotics, due to their poor tissue penetration. In order to treat S. aureus deep tissue infections we have developed an antibiotic delivery system using chitosan nanoparticles (CNPs). To enhance their tissue penetration these CNPs were further coated using lecithin (CLNPs). Antibiotic tigecycline was loaded into chitosan nanoparticles (tCNPs) and then coated with lecithin to generate lecithin coated tigecycline loaded chitosan nanoparticles (tCLNPs). The prepared nanoparticles were characterized using DLS, SEM, TEM and FT-IR. The prepared CNPs, tCNPs, CLNPs and tCLNPs have the size range of 85 +/- 10, 90 +/- 18, 188 +/- 5 and 235 +/- 20 nm, respectively. The tCLNPs shows more sustained release pattern of tigecycline. The antibacterial activity of the developed nanoparticles was confirmed against laboratory and clinical strains of S. aureus using in vitro and ex vivo experiments. The ex vivo skin and muscle permeation study ensures the enhanced delivery of tigecycline to the deeper tissue. The prepared nanoparticles were hemo-compatible and cyto-compatible. Our study suggests that the prepared tCLNPs can be effectively used for the treatment of S. aureus infected wounds. PMID- 26898358 TI - Opioid adjuvant strategy: improving opioid effectiveness. AB - Opioid analgesics continue to be the mainstay of pharmacologic treatment of moderate to severe pain. Many patients, particularly those suffering from chronic pain, require chronic high-dose analgesic therapy. Achieving clinical efficacy and tolerability of such treatment regimens is hampered by the appearance of opioid-induced side effects such as tolerance, hyperalgesia and withdrawal syndrome. Among the therapeutic options to improve the opioid effectiveness, this current review focuses on strategies combining opioids to other drugs that can modulate opioid-mediated effects. We will discuss about experimental evidences reported for several potential opioid adjuvants, including N-methyl-D-aspartate receptor antagonists, 5-HT7 agonists, sigma-1 antagonists, I2-R ligands, cholecystokinin antagonists, neuropeptide FF-R antagonists and toll-like receptor 4 antagonists. PMID- 26898357 TI - Endothelial to mesenchymal transition (EndMT): an active process in Chronic Obstructive Pulmonary Disease (COPD)? AB - Small airway fibrosis is the main contributor to physiological airway dysfunction in COPD. One potential mechanism contributing to small airway fibrosis is epithelial mesenchymal transition (EMT). When associated with angiogenesis (so called EMT-Type-3) it may well also be the link with the development of airway epithelial cancer, which is closely associated with COPD and predominantly in large airways. In a recent study published in Respiratory Research, Reimann and colleagues, showed increased expression of S100A4 in vasculature of human COPD and murine lungs. It is quite possible that the process of endothelial to mesenchymal transition (EndMT) is active in COPD lungs which we wish to comment on. PMID- 26898356 TI - Truncated yet functional viral protein produced via RNA polymerase slippage implies underestimated coding capacity of RNA viruses. AB - RNA viruses use various strategies to condense their genetic information into small genomes. Potyviruses not only use the polyprotein strategy, but also embed an open reading frame, pipo, in the P3 cistron in the -1 reading frame. PIPO is expressed as a fusion protein with the N-terminal half of P3 (P3N-PIPO) via transcriptional slippage of viral RNA-dependent RNA polymerase (RdRp). We herein show that clover yellow vein virus (ClYVV) produces a previously unidentified factor, P3N-ALT, in the +1 reading frame via transcriptional slippage at a conserved G(1-2)A(6-7) motif, as is the case for P3N-PIPO. The translation of P3N ALT terminates soon, and it is considered to be a C-terminal truncated form of P3. In planta experiments indicate that P3N-ALT functions in cell-to-cell movement along with P3N-PIPO. Hence, all three reading frames are used to produce functional proteins. Deep sequencing of ClYVV RNA from infected plants endorses the slippage by viral RdRp. Our findings unveil a virus strategy that optimizes the coding capacity. PMID- 26898359 TI - In vitro effects of plant essential oils on non-specific immune parameters of red drum, Sciaenops ocellatus L. AB - Phytochemicals such as plant essential oils (EOs) have been reported to favour various activities in the innate immune system of fish. Thus, the aim of this study was to verify the in vitro effect of three different plant EOs (Ocimum americanum, Cymbopogon flexuosus and Melaleuca alternifolia) on non-specific immune parameters and erythrocyte osmotic fragility of red drum, Sciaenops ocellatus. Concentrations of each plant EO evaluated in preparations of head kidney macrophages, blood leucocytes and blood plasma were as follows: 0.0 (control), 1.0, 2.0, 4.0, 8.0, and 16.0 MUg/ml. Red drum head-kidney macrophages significantly increased extracellular superoxide anion production when exposed (20 h) to O. americanum EO (1.0-8.0 MUg/ml) and C. flexuosus EO (2.0 and 4.0 MUg/ml). The respiratory burst of blood leucocytes (NBT test) significantly increased in all concentrations when compared to the respective control group, for all EOs. At the highest concentration (16.0 MUg/ml), C. flexuosus EO significantly inhibited the haemolytic activity of complement system in red drum blood after 1 h exposure. None of the tested concentrations significantly altered plasma lysozyme activity or erythrocyte osmotic fragility after exposing (1 h) red drum whole blood to each EO. This study demonstrated that these plant EOs are capable of triggering superoxide anion production in red drum leucocytes (head kidney macrophages and/or blood leucocytes). In vivo studies are warranted to address their potential as immunostimulants in the diet of red drum and other aquacultured species. PMID- 26898362 TI - Rapid intersystem crossings in anti bimanes. AB - We have carried out first principles electronic structure calculations on the ground and excited valence states of syn and anti bimanes. While syn bimanes fluoresce strongly after photoexcitation to the first excited singlet state (S1) and are commonly used as fluorophores in biological labeling studies, anti bimanes largely phosphoresce at low temperatures. We show that this is due to subtle differences in the energetic ordering of excited singlet and triplet states within the isomers. In particular, T2 in anti bimanes is characterized by a pi->pi* transition and large exchange interactions with the singlet counterpart cause it to lie below and energetically close to S1 at the Franck-Condon region. This opens up a pathway for very fast intersystem crossing (ca. 10(11) s(-1)) from the optically bright S1 state to the triplet manifold, which effectively quenches fluorescence. On the other hand, T2 is energetically inaccessible to S1 in syn bimanes and intersystem crossing via S1-> T1 cannot compete effectively with fluorescence to S0. We have also located minimum energy conical intersections between S0 and S1 in bimanes. However, these structures are significantly distorted from their equilibrium geometries as well as energetically much higher than S1 at the Franck-Condon region. They are therefore not expected to play a part in the photophysics of bimanes after excitation to S1. PMID- 26898361 TI - The impacts of increasing drought on forest dynamics, structure, and biodiversity in the United States. AB - We synthesize insights from current understanding of drought impacts at stand-to biogeographic scales, including management options, and we identify challenges to be addressed with new research. Large stand-level shifts underway in western forests already are showing the importance of interactions involving drought, insects, and fire. Diebacks, changes in composition and structure, and shifting range limits are widely observed. In the eastern US, the effects of increasing drought are becoming better understood at the level of individual trees, but this knowledge cannot yet be confidently translated to predictions of changing structure and diversity of forest stands. While eastern forests have not experienced the types of changes seen in western forests in recent decades, they too are vulnerable to drought and could experience significant changes with increased severity, frequency, or duration in drought. Throughout the continental United States, the combination of projected large climate-induced shifts in suitable habitat from modeling studies and limited potential for the rapid migration of tree populations suggests that changing tree and forest biogeography could substantially lag habitat shifts already underway. Forest management practices can partially ameliorate drought impacts through reductions in stand density, selection of drought-tolerant species and genotypes, artificial regeneration, and the development of multistructured stands. However, silvicultural treatments also could exacerbate drought impacts unless implemented with careful attention to site and stand characteristics. Gaps in our understanding should motivate new research on the effects of interactions involving climate and other species at the stand scale and how interactions and multiple responses are represented in models. This assessment indicates that, without a stronger empirical basis for drought impacts at the stand scale, more complex models may provide limited guidance. PMID- 26898363 TI - Sentinel lymph node biopsy in breast cancer New indications and our experience. AB - INTRODUCTION: Owing to complexity and difficulty regarding evaluation of all the regional lymph nodes, the Sentinel Lymph Node Biopsy (SLNB) has represented in recent years a suitable technique for setting lymph node status; it allows pathologists to focus on a small number of lymph nodes and stage patients with clinically negative lymph nodes; this sort of assessment leads surgeons to a correct approach; on the contrary, the presence of metastases makes advisable to perform Axillary Lymph Node Dissection (ALND). MATERIALS AND METHODS: From September 2008 to December 2013, 142 patients suffering from breast cancer were enrolled. Mean age was 54 years (range 37-80), in 88 (62%) patients the lesion was localized to the right breast, while in the remaining 54 (38%) the disease was localized in the left breast. Also in 85 (60%) patients, the tumor involved the upper-outer quadrant, in 24 (17%) the lower external quadrant, in 19 (13%) the upper-inner quadrant and in the remaining 14 (10%) the inferior-internal quadrant. RESULTS: There were neither intra nor post-operative complications. The all removed breast lesions were histologically malignant: 99 (70%) patients had a histological diagnosis of invasive ductal, 30 (21%) of invasive lobular, 9 (6%) ductal in situ and 4 (3%) of mixed invasive cancer. Sentinel Lymph Node (SLN) was always identified and it was extemporaneously positive in 62 cases (44%): 40 cases had macro-metastatic involvement whereas the remaining 22 cases had micro metastases only. The definitive histological examination confirmed the presence of micro-metastases in 18 cases, while in 2 cases there was a supra-staging to macro-metastases and in other 2 a sub-staging of Isolated Tumor Cells (ITC). None of the patients with micro-metastatic SLN involvement developed recurrence within 24 months, whereas only one patient died after one year owing to at distance dissemination. CONCLUSION: Lymph node status has increasingly been getting one of the most important prognostic factor. Consequently the bigger the tumor nodal involvement appears the worse the prognosis becomes. Our data confirm the main role of SLNB on managing surgical treatment of breast cancer. KEY WORDS: Biopsy, Breast cancer, Sentinel lymph node. PMID- 26898360 TI - Tissue repair in myxobacteria: A cooperative strategy to heal cellular damage. AB - Damage repair is a fundamental requirement of all life as organisms find themselves in challenging and fluctuating environments. In particular, damage to the barrier between an organism and its environment (e.g. skin, plasma membrane, bacterial cell envelope) is frequent because these organs/organelles directly interact with the external world. Here, we discuss the general strategies that bacteria use to cope with damage to their cell envelope and their repair limits. We then describe a novel damage-coping mechanism used by multicellular myxobacteria. We propose that cell-cell transfer of membrane material within a population serves as a wound-healing strategy and provide evidence for its utility. We suggest that--similar to how tissues in eukaryotes have evolved cooperative methods of damage repair--so too have some bacteria that live a multicellular lifestyle. PMID- 26898364 TI - Antimicrobials: beta-lactam sensor discovered. PMID- 26898365 TI - Environmental microbiology: Pumping carbon to the deep ocean. PMID- 26898366 TI - Bacterial physiology: It's never too late for CRISPR RNases. PMID- 26898367 TI - Primary Immunodeficiency Diseases in Aguascalientes, Mexico: Results from an Educational Program. AB - PURPOSE: Primary immunodeficiencies (PIDs) are a heterogeneous group of disorders characterized mainly by recurrent infections. Late diagnosis remains as one of the main issues to solve. We aimed to increase PID diagnosis in Aguascalientes, a 1.3 million inhabitants state in the center of Mexico, and to describe the clinical features of such patients. METHODS: We developed an educational program for health personnel and general public; patients with possible PID were referred to a State University clinical center from December 2011 to December 2012. The patients were evaluated at the clinic and their definitive diagnosis pursued through laboratory, molecular and genetic assays. We describe the findings of those patients and analyze the impact of the program in terms of number of referrals. RESULTS: After 41 talks and 12 media appearances 151 patients were referred for evaluation. Fifteen (9.9%) were diagnosed with PID: five (33%) had antibody deficiencies, seven (47%) Well-defined syndromes, two (13%) Severe combined Immunodeficiency (SCID) and one case (7%) of an innate immune deficiency. All of the 15 PID patients had been referred by physicians, as opposed to the public. We estimated a "number needed to teach" of 75 physicians to get one PID patient referral. CONCLUSION: Educational programs are a fundamental part of the global efforts to increase PID diagnosis and care. To be successful, such programs should include public relations, reach for first contact physicians, and aim to develop an efficient referral network with molecular diagnostic capability. Enhancing medical knowledge on PID is a successful strategy to improve early diagnosis and treatment. PMID- 26898368 TI - Disease eradication on large industrial farms. AB - Many modern farms exhibit all-in-all-out dynamics in which entire cohorts of livestock are removed from a farm before a new cohort is introduced. This industrialization has enabled diseases to spread rapidly within farms. Here we look at one such example, Marek's disease. Marek's disease is an economically important disease of poultry. The disease is transmitted indirectly, enabling the spread of disease between cohorts of chickens who have never come into physical contact. We develop a model which allows us to track the transmission of disease within a barn and between subsequent cohorts of chickens occupying the barn. It is described by a system of impulsive differential equations. We determine the conditions that lead to disease eradication. For a given level of transmission we find that disease eradication is possible if the cohort length is short enough and/or the cohort size is small enough. Marek's disease can also be eradicated from a farm if the cleaning effort between cohorts is large enough. Importantly complete cleaning is not required for eradication and the threshold cleaning effort needed declines as both cohort duration and size decrease. PMID- 26898370 TI - Migration from printing inks in multilayer food packaging materials by GC-MS analysis and pattern recognition with chemometrics. AB - Inks and varnishes used in food packaging multilayer materials can contain different substances that are potential migrants when packaging is in contact with food. Although printing inks are applied on the external layer, they can migrate due to set-off phenomena. In order to assess food safety, migration tests were performed from two materials sets: set A based on paper and set B based on PET; both contained inks. Migration was performed to four food simulants (EtOH 50%, isooctane, EtOH 95% and Tenax((r))) and the volatile compounds profile was analysed by GC-MS. The effect of presence/absence of inks and varnishes and also their position in the material was studied. A total of 149 volatile compounds were found in migration from set A and 156 from set B materials, some of them came from inks. Quantitative analysis and a principal component analysis were performed in order to identify patterns among sample groups. PMID- 26898369 TI - Urine proteome analysis as a discovery tool in patients with deep vein thrombosis and pulmonary embolism. AB - PURPOSE: Early and accurate detection of deep vein thrombosis (DVT) is an important clinical need. Based on the hypothesis that urinary peptides may hold information on DVT in conjunction with pulmonary embolism (PE), the study was aimed at identifying such peptide biomarkers using capillary electrophoresis coupled mass spectrometry. EXPERIMENTAL DESIGN: Patients with symptoms of unprovoked/idiopathic DVT and/or PE were examined by doppler-sonography or angio computed tomography. Urinary proteome analysis allowed for identification of respective peptide biomarkers. To confirm their biological relevance, we induced PE in mice and assessed human ex vivo thrombi. RESULTS: We identified 62 urinary peptides as DVT-specific biomarkers, i.e. fragments of collagen type I and a fragment of fibrinogen beta-chain. The presence of fibrinogen alpha/beta in the acute thrombus, and collagen type I and osteopontin in the older, organized thrombus was demonstrated. The classifier DVT62 established through support vector machine (SVM) modeling based on the 62 identified peptides was validated in an independent cohort of 47 subjects (six cases and 41 controls) with a sensitivity of 100% and specificity of 83%. CONCLUSIONS AND CLINICAL RELEVANCE: Urine proteome analysis enabled the detection of DVT-specific peptides, which were validated in human and mouse tissue. Furthermore, it allowed for the establishment of an urinary-proteome based classifier that is relatively specific for DVT. The data provide the basis for assessment of these biomarkers in a prospective clinical study. PMID- 26898371 TI - The attentive homunculus: ERP evidence for somatotopic allocation of attention in tactile search. AB - Our brain constantly receives tactile information from the body's surface. We often only become aware of this information when directing our attention towards the body. Here, we report a study investigating the behavioural and neural response when selecting a target amongst distractor vibrations presented simultaneously to several locations either across the hands or body. Comparable visual search studies have revealed the N2pc as the neural correlate of visual selective attention. Analogously, we describe an enhanced negativity contralateral to the tactile target side. This effect is strongest over somatosensory areas and lasts approximately 200ms from the onset of the somatosensory N140 ERP component. Based on these characteristics we named this electrophysiological signature of attentional tactile target selection during tactile search the N140-central-contralateral (N140cc). Furthermore, we present supporting evince that the N140cc reflects attentional enhancement of target rather than suppression of distractor locations; the component was not reliably altered by distractor but rather by target location changes. Taken together, our findings present a novel electrophysiological marker of tactile search and show how attentional selection of touch operates by mainly enhancing task relevant locations within the somatosensory homunculus. PMID- 26898372 TI - Temporal judgments in multi-sensory space. AB - To successfully interact with the environment requires a combination of stimulus recognition as well as localization in both space and time, with information moreover coming from multiple senses. Several studies have shown that auditory stimuli last subjectively longer than visual ones of equal duration. Recently, it has also been suggested that stimulus position affects duration perception. The present study investigated how lateral spatial presentation influences sub-second visual and auditory duration judgments. Five experiments were conducted using the duration discrimination paradigm, wherein two stimuli are presented sequentially and participants are asked to judge whether the second stimulus (comparison) is shorter or longer in duration than the first (standard). The number of stimulus positions and the way in which different modality trials were presented (mixed or blocked) varied. Additionally, comparisons were made either within or across modalities. No stable effect of location itself was found. However, in mixed modality experiments there was a clear over-estimation of duration in visual trials when the location of the comparison was different from the standard. This effect was reversed in the same location trials. Auditory judgments were unaffected by location manipulations. Based on these results, we propose the existence of an error-mechanism, according to which a specific duration is added in order to compensate for the loss of duration perception caused by spatial attention shifts between different locations. This mechanism is revealed in spatial and modality-mixed circumstances wherein its over-activation results in a systematic temporal bias. PMID- 26898374 TI - Modelling an electrochemically roughened porous platinum electrode for water oxidation. AB - Pt is usually not considered as an efficient catalyst for water oxidation. Here, we report a design-of-experiment approach for modelling the roughness of an electrochemically roughened Pt electrode for water oxidation. The results indicate significant interaction between oxidation and reduction potentials on surface roughness and the porous Pt exhibits greatly improved catalytic activity for oxygen evolution in acid which is comparable to the benchmark catalyst RuO2. PMID- 26898373 TI - CEA in breast ductal secretions as a promising biomarker for the diagnosis of breast cancer: a systematic review and meta-analysis. AB - PURPOSE: Other studies have shown that levels of carcinoembryonic antigen (CEA) in breast ductal secretions (BDS) differ significantly between breast cancer (BC) patients and healthy individuals, providing direct evidence for CEA in BDS as a promising biomarker for BC. This meta-analysis was designed to assess the potential diagnostic value of CEA in BDS. METHODS: Relevant articles were retrieved from Embase, Pubmed, and the Cochrane Library. Sensitivity, specificity, and diagnostic odds ratio (DOR) of CEA in BDS for diagnosing BC were pooled using random effects models. SROC and the area under the curve (AUC) were used to estimate overall diagnostic performance. RESULTS: This meta-analysis comprised five studies with a total of 340 BC patients and 448 healthy controls. For CEA in BDS, the pooled sensitivity, specificity, and DOR to diagnose BC were 58 % [95 % confidence interval (CI): 52-63 %], 87 % (95 % CI: 84-90 %), and 7.07 (95 % CI: 3.10-16.12), respectively. Moreover, the AUC of CEA in the diagnosis of BC was 0.8570. CONCLUSIONS: CEA in BDS is a promising biomarker in the diagnosis of BC and should be evaluated as a standard screening tool upon verification of our results in a larger study population. PMID- 26898375 TI - Psychometric properties and feasibility of instruments for the detection of delirium in older hospitalized patients: a systematic review. AB - OBJECTIVE: Delirium is a serious and common complication among older hospitalized patients and is a predictor of many adverse outcomes. However, up to 72% of delirium incidents are unrecognized or misdiagnosed. The aim of this systematic review is to determine the validity, reliability, and feasibility of instruments for the detection of delirium in older hospitalized patients. METHODS: A systematic literature search was conducted. The inclusion criteria were a mean or median age of 65+ years, the use of the Diagnostic and Statistical Manual of Mental Disorders or International Classification of Diseases-10 as a reference standard, and publication in English. All included studies underwent a quality assessment (QUADAS-2). RESULTS: Forty-three of the 3.790 identified studies were relevant to the review, describing 28 instruments. Quality assessment resulted in 37 studies with a positive quality assessment, describing 23 instruments. Five instruments (Delirium Observation Scale (DOS), Nursing Delirium Screening Scale (Nu-DESC), Confusion Assessment Method (CAM), CAM-Intensive Care Unit (ICU), and Delirium Rating Scale-Revised-98) were described in three or more methodologically sound studies. The Delirium Observation Screening Scale (DOS) and Nu-DESC are observational instruments with good psychometric properties, but the Nu-DESC is shorter and has been validated in more languages. The CAM, CAM ICU, and Delirium Rating Scale-Revised-98 (DRS-R-98) are instruments with both observational and interactive components. The CAM is the most widely studied and demonstrates the best psychometric properties. CONCLUSION: Timely detection of delirium might reduce the negative outcomes of delirium in the long term. The Nu DESC and CAM appear to be the most adequate instruments for detecting delirium. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26898376 TI - In Response. PMID- 26898378 TI - Plasmon Response and Electron Dynamics in Charged Metallic Nanoparticles. AB - Using the time-dependent density functional theory, we perform quantum calculations of the electron dynamics in small charged metallic nanoparticles (clusters) of spherical geometry. We show that the excess charge is accumulated at the surface of the nanoparticle within a narrow layer given by the typical screening distance of the electronic system. As a consequence, for nanoparticles in vacuum, the dipolar plasmon mode displays only a small frequency shift upon charging. We obtain a blue shift for positively charged clusters and a red shift for negatively charged clusters, consistent with the change of the electron spill out from the nanoparticle boundaries. For negatively charged clusters, the Fermi level is eventually promoted above the vacuum level leading to the decay of the excess charge via resonant electron transfer into the continuum. We show that, depending on the charge, the process of electron loss can be very fast, on the femtosecond time scale. Our results are of great relevance to correctly interpret the optical response of the nanoparticles obtained in electrochemistry, and demonstrate that the measured shift of the plasmon resonances upon charging of nanoparticles cannot be explained without account for the surface chemistry and the dielectric environment. PMID- 26898380 TI - A novel HLA-B*15 allele, HLA-B*15:326, was identified in a Chinese bone marrow donor. AB - HLA-B*15:326 has one base substitution at position 176G>A in exon 2 compared with HLA-B*15:01:01:01. PMID- 26898379 TI - Development and in Vitro Evaluation of a Microbicide Gel Formulation for a Novel Non-Nucleoside Reverse Transcriptase Inhibitor Belonging to the N Dihydroalkyloxybenzyloxopyrimidines (N-DABOs) Family. AB - Preventing HIV transmission by the use of a vaginal microbicide is a topic of considerable interest in the fight against AIDS. Both a potent anti-HIV agent and an efficient formulation are required to develop a successful microbicide. In this regard, molecules able to inhibit the HIV replication before the integration of the viral DNA into the genetic material of the host cells, such as entry inhibitors or reverse transcriptase inhibitors (RTIs), are ideal candidates for prevention purpose. Among RTIs, S- and N-dihydroalkyloxybenzyloxopyrimidines (S DABOs and N-DABOs) are interesting compounds active at nanomolar concentration against wild type of RT and with a very interesting activity against RT mutations. Herein, novel N-DABOs were synthesized and tested as anti-HIV agents. Furthermore, their mode of binding was studied by molecular modeling. At the same time, a vaginal microbicide gel formulation was developed and tested for one of the most promising candidates. PMID- 26898381 TI - WITHDRAWN: Erratum to "Evaluation of next generation mtGenome sequencing using the Ion Torrent Personal Genome Machine (PGM)" [Forensic Sci. Int.: Genet. 7 (2013) 543-549]. AB - The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://dx.doi.org/10.1016/j.fsigen.2013.09.007. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. PMID- 26898382 TI - Bone Metabolism in a Large Cohort of Patients with Systemic Sclerosis. AB - The aim of this study was to evaluate in a large size cohort of SSc patients bone mineral density (BMD) and to analyze its possible determinants. 106 consecutive outpatients affected by SSc were enrolled and completely evaluated for bone metabolism and SSc characteristics. For the statistical analysis, we preferred Z score to BMD or T score since the population was composed of patients of different ages and of both sexes. Mean neck Z score was significantly lower than 0. No significant differences were found for other sites. Female patients were shown to have a total femur and neck Z score significantly lower than 0 (p = 0.028 and p < 0.001, respectively). 13 % of patients had at least one morphometric non-clinical vertebral fracture. In univariate analysis, total femur Z score was lower in female (p = 0.050) and positively correlates with BMI (p = 0.001), neck Z score positively correlates with age (p = 0.016), and whole body Z score positively correlates with BMI (p < 0.001). No correlations were found for lumbar Z score. The multivariate analysis confirmed the positive correlation between BMI and total femur and whole body Z score and between age and neck femur Z score (p = 0.005, p < 0.001 and p = 0.040, respectively). Lung involvement was shown to correlate with a lower whole body Z score in multivariate analysis (p = 0.037). We found a modest risk of low BMD in patients with SSc and the important protective role of BMI. Patients with lung involvement showed lower whole body Z score. PMID- 26898383 TI - A huge thoracic spinal giant cell tumor of the tendon sheaths with an intact neurologic function. PMID- 26898377 TI - Antinociceptive effect of a novel armed spider peptide Tx3-5 in pathological pain models in mice. AB - The venom of the Brazilian armed spider Phoneutria nigriventer is a rich source of biologically active peptides that have potential as analgesic drugs. In this study, we investigated the analgesic and adverse effects of peptide 3-5 (Tx3-5), purified from P. nigriventer venom, in several mouse models of pain. Tx3-5 was administered by intrathecal injection to mice selected as models of postoperative (plantar incision), neuropathic (partial sciatic nerve ligation) and cancer related pain (inoculation with melanoma cells) in animals that were either sensitive or tolerant to morphine. Intrathecal administration of Tx3-5 (3-300 fmol/site) in mice could either prevent or reverse postoperative nociception, with a 50 % inhibitory dose (ID50) of 16.6 (3.2-87.2) fmol/site and a maximum inhibition of 87 +/- 10 % at a dose of 30 fmol/site. Its effect was prevented by the selective activator of L-type calcium channel Bay-K8644 (10 MUg/site). Tx3-5 (30 fmol/site) also produced a partial antinociceptive effect in a neuropathic pain model (inhibition of 67 +/- 10 %). Additionally, treatment with Tx3-5 (30 fmol/site) nearly abolished cancer-related nociception with similar efficacy in both morphine-sensitive and morphine-tolerant mice (96 +/- 7 and 100 % inhibition, respectively). Notably, Tx3-5 did not produce visible adverse effects at doses that produced antinociception and presented a TD50 of 1125 (893-1418) fmol/site. Finally, Tx3-5 did not alter the normal mechanical or thermal sensitivity of the animals or cause immunogenicity. Our results suggest that Tx3 5 is a strong drug candidate for the treatment of painful conditions. PMID- 26898385 TI - Growing rods in early-onset scoliosis. PMID- 26898384 TI - Correlation between preoperative spinopelvic alignment and risk of proximal junctional kyphosis after posterior-only surgical correction of Scheuermann kyphosis. AB - BACKGROUND CONTEXT: Surgical correction of Scheuermann kyphosis (SK) is challenging and plagued by relatively high rates of proximal junctional kyphosis and failure (PJK and PJF). Normal sagittal alignment of the spine is determined by pelvic geometric parameters. How these parameters correlate with the risk of developing PJK in SK is not known. PURPOSE: The study aimed to investigate the relationship between preoperative and postoperative spinopelvic alignment and occurrence of PJK and PJF. STUDY DESIGN/SETTING: This is a retrospective observational cohort study. PATIENT SAMPLE: The sample included 37 patients who underwent posterior correction of SK from January 2006 to December 2012. OUTCOME MEASURES: The outcome measure was correlation analysis between preoperative and postoperative spinopelvic alignment parameters and the development of PJK over the course of the study period. METHODS: Whole spine x-rays obtained before surgery, 3 months after surgery, and at the latest follow-up were analyzed. The following parameters were measured: thoracic kyphosis (TK), lumbar lordosis (LL), sagittal vertical axis (SVA), pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS). The development of PJK was considered the primary end point of the study. Patient population was split into a control and a PJK group; repeated measures analysis of variance was used to assess group and time differences. RESULTS: Seven patients developed PJK over the study period. Although the severity of the preoperative deformity (TK) did not differ significantly between the two groups, preoperative PI was significantly higher in the PJK group (51.9 degrees C+/-8.6 degrees C vs. 42.7 degrees C+/-8.8 degrees C, p=.018). Postoperative correction of TK was similar between the two groups (39.3% and 41.2%, p=.678) and final LL did not differ as well (53.6 degrees C+/-9.2 degrees C vs. 51.3 degrees C+/-11.5 degrees C). However, because PJK patients had larger preoperative PI values, a significant deficit of LL was observed at final follow up in this group compared with the control group (DeltaLL -10.5 degrees C+/-9.8 degrees C vs. 0.6 degrees C+/-10.5 degrees C, p=.013). CONCLUSIONS: Scheuermann kyphosis patients who developed PJK appeared to have a significant postoperative deficit of LL (lumbopelvic mismatch). Lumbar lordosis decreases after surgery following correction of TK; therefore, TK correction should be planned according to preoperative PI values to avoid excessive reduction of LL in patients with higher PI values. PMID- 26898386 TI - Biomass derived solvents for the scalable production of single layered graphene from graphite. AB - Among four different biomass derived green and sustainable solvents namely levulinic acid (LA), ethyl lactate (EL), gamma-valerolactone (GVL) and formic acid (FA) only LA was found to exfoliate graphite to single and few layered graphene sheets. During exfoliation, the formation of LA crystals embedded with single layered graphene sheets was observed. The process is scalable and the solvent can be recovered and reused in five subsequent cycles of exfoliation for the large scale production of graphene sheets. PMID- 26898387 TI - The effects of training status and muscle action on muscle activation of the vastus lateralis. AB - This study examined the electromyographic amplitude-force relationships for 5 (age = 19.20 +/- 0.45 yrs) aerobically-trained, 5 (age = 25 +/- 4.53 yrs) resistance-trained, and 5 (age = 21.20 +/- 2.17 yrs) sedentary individuals. Participants performed an isometric trapezoidal muscle action at 60% maximal voluntary contraction of the leg extensors that included linearly increasing, steady force, and linearly decreasing muscle actions. Electromyography was recorded from the vastus lateralis. The b (slopes) and a (y-intercepts) terms were calculated from the natural log-transformed electromyographic amplitude force relationships (linearly increasing and decreasing segments) for each participant. An average of the electromyographic amplitude was calculated for the entire steady force segment. The b terms for the resistance-trained (1.384 +/- 0.261) were greater than the aerobically-trained (0.886 +/- 0.130, P = 0.003) and sedentary (0.955 +/- 0.105, P = 0.008) participants during the linearly increasing segment, whereas, there were no differences in b terms among training statuses for the linearly decreasing segment. The b terms for the resistance trained were greater (P = 0.019) during the linearly increasing segment than decreasing segment (1.186 +/- 0.181), however, the b terms for the aerobically trained were lower (P = 0.017) during the linearly increasing than decreasing segment (1.054 +/- 0.176). The a terms from the log-transformed electromyographic amplitude- force relationships and electromyographic amplitude during the steady force segment were not different among training statuses (P = 0.187, P = 0.910). The linearity of the electromyographic amplitude patterns of response (b terms) recording during increasing and decreasing muscle actions may provide insight on motor unit control strategy differences as a result of exercise training status and muscle action, however, the a terms of these patterns and electromyographic amplitude during a steady force contraction did not distinguish among training statuses. PMID- 26898388 TI - Revitalizing sociology: urban life and mental illness between history and the present. AB - This paper proposes a re-thinking of the relationship between sociology and the biological sciences. Tracing lines of connection between the history of sociology and the contemporary landscape of biology, the paper argues for a reconfiguration of this relationship beyond popular rhetorics of 'biologization' or 'medicalization'. At the heart of the paper is a claim that, today, there are some potent new frames for re-imagining the traffic between sociological and biological research - even for 'revitalizing' the sociological enterprise as such. The paper threads this argument through one empirical case: the relationship between urban life and mental illness. In its first section, it shows how this relationship enlivened both early psychiatric epidemiology, and some forms of the new discipline of sociology; it then traces the historical division of these sciences, as the sociological investment in psychiatric questions waned, and 'the social' become marginalized within an increasingly 'biological' psychiatry. In its third section, however, the paper shows how this relationship has lately been revivified, but now by a nuanced epigenetic and neurobiological attention to the links between mental health and urban life. What role can sociology play here? In its final section, the paper shows how this older sociology, with its lively interest in the psychiatric and neurobiological vicissitudes of urban social life, can be our guide in helping to identify intersections between sociological and biological attention. With a new century now underway, the paper concludes by suggesting that the relationship between urban life and mental illness may prove a core testing-ground for a 'revitalized' sociology. PMID- 26898389 TI - Patient-Reported Mobility: A Systematic Review. AB - OBJECTIVES: To identify the self-administered instruments to assess mobility in adults with disability, to link the mobility assessed by these instruments to the International Classification of Functioning, Disability and Health (ICF), and to evaluate their methodological quality. DATA SOURCES: Scopus, Science Direct, and Web of Science were systematically searched up to July 2015. STUDY SELECTION: Studies on the development and validation of self-administered questionnaires in which at least half of the items were related to movement or mobility were included. DATA EXTRACTION: The mobility assessed by the instruments was classified according to the ICF categories. The methodological quality was assessed according to the Consensus-based Standards for the Selection of Health Measurement Instruments checklist. DATA SYNTHESIS: Of 5791 articles, 34 studies were eligible for inclusion. Only 10 of the instruments contained items that exclusively assessed mobility. The most frequently linked ICF categories were "changing basic body position" (19.4%), "walking" (14.8%), and "moving around" (13.5%). Measurement properties evaluated included internal consistency (5 studies), reliability (5 studies), measurement error (1 study), content validity (9 studies), structural validity (4 studies), hypotheses testing (6 studies), and responsiveness (1 study). Only content validity obtained the highest quality, probably because the studies included in the review reported the development and initial validation of the instruments. CONCLUSIONS: Self-administered mobility questionnaires published in the scientific literature assess mobility activities rather than functions related to movement, and do so from the perspective of disability, frequently including self-care and domestic life as domains for assessment. The instruments that presented the highest methodological quality were the Outpatient Physical Therapy Improvement in Movement Assessment Log, the Movement Ability Measure, and the Mobility Activities Measure for Inpatient Rehabilitation Settings. PMID- 26898390 TI - Influence of Age Alone, and Age Combined With Pinprick, on Recovery of Walking Function in Motor Complete, Sensory Incomplete Spinal Cord Injury. AB - OBJECTIVE: To determine if age, pinprick scores in the lower extremities, and neurologic severity of injury influence recovery of ambulation in persons with motor complete, sensory incomplete (American Spinal Injury Association Impairment Scale [AIS] grade B) spinal cord injury (SCI) 1 year after initial injury. DESIGN: This retrospective analysis examined subjects with AIS grade B from the Spinal Cord Injury Model System (SCIMS) database from 2006 to 2015. The baseline neurologic examination at rehabilitation admission (2-4wk postinjury) was used for comparison with 1-year outcome measures of locomotion. SETTING: Fifteen acute inpatient rehabilitation centers (participants in the SCIMS database). PARTICIPANTS: Participants with AIS grade B SCI (N=249) were enrolled in the SCIMS database in 2 cycles (2006-2010 and 2011-2015). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Household ambulation at 1 year by FONE-FIM and by direct interview, as part of the annual neurologic exam; change in American Spinal Injury Association score 1 year postinjury. RESULTS: Findings demonstrate a statistically nonsignificant increase in likelihood of walking for those age <50 years compared with those age >=50 years (relative risk [RR]=1.99; 95% confidence interval, 0.80-3.04). Presence of pinprick in at least one half of the lower-extremity dermatomes L2-S1 was associated with higher likelihood of walking (RR=5.57, P=.0023). Pinprick was significant for patients age <50 years (RR=4.58, P=.0090) but not for those age >=50 years (P=.15). CONCLUSIONS: Compared with younger individuals, participants age >=50 years with AIS grade B SCI are less likely to achieve walking function 1 year postinjury. Likewise, preservation of pinprick sensation postinjury in the majority of lower-extremity dermatomes L2-S1 increases the chances of walking in individuals age <50 years. PMID- 26898391 TI - Systemic and local anti-Mullerian hormone reflects differences in the reproduction potential of Zebu and European type cattle. AB - This study was conducted to evaluate plasma anti-Mullerian hormone (Pl AMH), follicular fluid AMH (FF AMH) and granulosa cell AMH transcript (GC AMH) levels and their relationships with reproductive parameters in two cattle subspecies, Bos taurus indicus (Zebu), and Bos taurus taurus (European type cattle). Two dimensional ultrasound examination and serum collection were performed on Zebu, European type and crossbreed cows to determine antral follicle count (AFC), ovary diameter (OD) and Pl AMH concentration. Slaughterhouse ovaries for Zebu and European type cattle were collected to determine FF AMH concentrations, GC AMH RNA levels, AFC, oocyte number, cleavage and blastocyst rate. Additionally GC AMH receptor 2 (AMHR2) RNA level was measured for European type cattle. Relationship between AMH and reproductive parameters was found to be significantly greater in Zebu compared to European cattle. Average Pl AMH mean +/- SE for Zebu and European cattle was 0.77 +/- 0.09 and 0.33 +/- 0.24 ng/ml respectively (p = 0.01), whereas average antral FF AMH mean +/- SE for Zebu and European cattle was 4934.3 +/- 568.5 and 2977.9 +/- 214.1 ng/ml respectively (p < 0.05). This is the first published report of FF and GC AMH in Zebu cattle. Levels of GC AMHR2 RNA in European cattle were correlated to oocyte number (p = 0.01). Crossbred animals were found more similar to their maternal Zebu counterparts with respect to their Pl AMH to AFC and OD relationships. These results demonstrate that AMH reflects differences between reproduction potential of the two cattle subspecies therefore can potentially be used as a reproductive marker. Furthermore these results reinforce the importance of separately considering the genetic backgrounds of animals when collecting or interpreting bovine AMH data for reproductive performance. PMID- 26898392 TI - Effects of a long-day light programme on the motility and membrane integrity of cooled-stored and cyropreserved semen in Shetland pony stallions. AB - Increasing day length in spring stimulates reproductive functions in horses. In this study, we have analysed the effect of artificial long days on the quality of cooled-stored and cryopreserved semen in Shetland stallions. Stallions of the treatment group (AL, n = 8) were exposed to 16 h light and 8h darkness from 15th December to 20th March while control stallions (CON, n = 7) were kept under natural photoperiod. Semen was collected once weekly and processed for cooled storage and cryopreservation once per month. Total and progressive motility and percentage of membrane intact spermatozoa were analysed at 24, 48 and 72 h of cooled-storage and after freezing-thawing, respectively. Total and progressive motility and membrane integrity decreased during cooled-storage for 72 h in each month and both groups (p < 0.001). All these parameters were lower in CON versus AL stallions (p < 0.05) and the decrease was more pronounced in group CON (storage time x group p < 0.05). Differences between groups decreased throughout the observation period from January (p < 0.05 between groups) to July (e.g. total motility after 72 h of cooled-storage in January for group AL 80 +/- 3 and group CON 49 +/- 12%, respective values in July, 83 +/- 2 and 72 +/- 6%). Neither total and progressive motility nor percentage of membrane-intact and morphologically defect spermatozoa in frozen-thawed semen differed between groups and months. In conclusion, motility of cooled-stored semen was reduced in January and increased in stallions kept under a long day light programme for at least 30 days. PMID- 26898393 TI - Superovulation in wood bison (Bison bison athabascae): Effects of progesterone, treatment protocol and gonadotropin preparations for the induction of ovulation. AB - Experiments were done to determine the ovarian response and embryo production following superstimulation of wood bison. In Experiment 1 (Anovulatory season), the efficacy of pLH vs. hCG for inducing ovulation was compared in wood bison superstimulated with a single dose of pFSH in 0.5% hyaluronan and the effect of exogenous progesterone (PRID) on superovulatory response and embryo quality was examined. In Experiment 2 (Ovulatory season), the efficacy of pLH vs. hCG for the induction of ovulation was compared in wood bison superstimulated with pFSH in a single intramuscular dose vs. a two-dose regimen 48 h apart (split dose) in 0.5% hyaluronan. In Experiment 1, the number of CL was greater (P < 0.05) in bison treated with hCG than pLH (6.6 +/- 1.8 vs. 2.8 +/- 0.8) and in those that were not given PRID (6.0 +/- 1.5 vs. 2.7 +/- 1.0). There was no effect of progesterone treatment on embryo quality. In Experiment 2, the number of CL was greater (P < 0.05) in bison treated with hCG than with pLH (6.3 +/- 0.8 vs. 3.8 +/- 1.2) and in bison superstimulated with split dose vs. single dose of FSH (7.1 +/- 0.9 vs. 3.0 +/- 0.8). The number of ova/embryos and freezable embryos did not differ among groups in either experiment. In conclusion, hCG induced a greater ovulatory response than pLH in both seasons. Two doses of FSH induced the greatest superovulatory response during the ovulatory season. Exogenous progesterone did not improve embryo quality during the anovulatory season. PMID- 26898394 TI - Voice Signals Produced With Jitter Through a Stochastic One-mass Mechanical Model. AB - BACKGROUND: The quasiperiodic oscillation of the vocal folds causes perturbations in the length of the glottal cycles, which are known as jitter. The observation of the glottal cycles variations suggests that jitter is a random phenomenon described by random deviations of the glottal cycle lengths in relation to a corresponding mean value and, in general, its values are expressed as a percentage of the duration of the glottal pulse. OBJECTIVE: The objective of this paper is the construction of a stochastic model for jitter using a one-mass mechanical model of the vocal folds, which assumes complete right-left symmetry of the vocal folds, and which considers motions of the vocal folds only in the horizontal direction. STUDY DESIGN: The jitter has been the subject for researchers due to its important applications such as the identification of pathological voices (nodules in the vocal folds, paralysis of the vocal folds, or even, the vocal aging, among others). Large values for jitter variations can indicate a pathological characteristic of the voice. METHOD: The corresponding stiffness of each vocal fold is considered as a stochastic process, and its modeling is proposed. RESULTS: The probability density function of the fundamental frequency related to the voice signals produced are constructed and compared for different levels of jitter. Some samples of synthesized voices in these cases are obtained. CONCLUSIONS: It is showed that jitter could be obtained using the model proposed. The Praat software was also used to verify the measures of jitter in the synthesized voice signals. PMID- 26898395 TI - Dysphonia Severity Index in Typically Developing Indian Children. AB - BACKGROUND: Dysphonia is a variation in an individual's quality, pitch, or loudness from the voice characteristics typical of a speaker of similar age, gender, cultural background, and geographic location. Dysphonia Severity Index (DSI) is a recognized assessment tool based on a weighted combination of maximum phonation time, highest frequency, lowest intensity, and jitter (%) of an individual. Although dysphonia in adults is accurately evaluated using DSI, standard reference values for school-age children have not been studied. AIM: This study aims to document the DSI scores in typically developing children (8-12 years). METHOD: A total of 42 typically developing children (8-12 years) without complaint of voice problem on the day of testing participated in the study. DSI was computed by substituting the raw scores of substituent parameters: maximum phonation time, highest frequency, lowest intensity, and jitter% using various modules of CSL 4500 software. RESULTS: The average DSI values obtained in children were 2.9 (1.23) and 3.8 (1.29) for males and females, respectively. DSI values are found to be significantly higher (P = 0.027) for females than those for males in Indian children. This could be attributed to the anatomical and behavioral differences among females and males. Further, pubertal changes set in earlier for females approximating an adult-like physiology, thereby leading to higher DSI values in them. CONCLUSION: The mean DSI value obtained for male and female Indian children can be used as a preliminary reference data against which the DSI values of school-age children with dysphonia can be compared. PMID- 26898396 TI - Surgical Management of Charcot Deformity for the Foot and Ankle-Radiologic Outcome After Internal/External Fixation. AB - Charcot neuropathy (CN) is a severe joint disease that makes surgical planning very challenging, because it is combined with ankle instability, serious deformities, and recurrent ulceration. The aim of the present study was to examine the rate of bone fusion after external or internal fixation in patients with CN. We retrospectively examined 58 patients with CN who had undergone reconstruction of the ankle either with tibiotalocalcaneal or tibiocalcaneal arthrodesis. The mean age was 59.1 (range 26 to 81) years at surgery. Of the 58 patients, 38 were treated using intramedullary nail arthrodesis and 19 using an external fixator (1 patient received neither). At a mean follow-up period of 31.3 (range 12 to 57) months, limb salvage and bone fusion had been achieved in 94.83%. The mean time to bone fusion was 12 (range 6 to 18) months. Three patients (5.2%) required a more proximal amputation. All but these 3 patients gained independent mobilization in custom feet orthoses or off the shelf orthoses. Of the 58 patients in the present cohort, 56 (96.6%) would undergo surgery again. In conclusion, internal and external fixation both lead to promising results in the treatment of CN. Internal fixation should be preferred when no indications of ulcer or infection are present. PMID- 26898397 TI - Acute Limb-Threatening Ischemia Associated With Antiphospholipid Syndrome: A Report of Two Cases. AB - Acute limb ischemia results from sudden deterioration in the arterial supply to the limb, occasionally leading to limb loss or fatality. Antiphospholipid syndrome (APS) is known to induce acute limb ischemia among the various etiologies responsible for arterial obstruction. APS is a systemic autoimmune disorder characterized by a combination of arterial and/or venous thrombosis and limb loss. It is often accompanied by a mild-to-moderate thrombocytopenia and elevated titers of antiphospholipid antibodies, including the lupus anticoagulant and the anticardiolipin antibodies. In the present report, we present 2 cases of acute limb ischemia due to APS associated with systemic lupus erythematosus. Angiography revealed arterial obstruction distal to the popliteal artery in both patients, and each patient eventually underwent below-the-knee amputation. Surgeons treating acute limb ischemia should remember APS, although this disease might not be common in daily clinical practice. PMID- 26898398 TI - Mortality After Nontraumatic Major Amputation Among Patients With Diabetes and Peripheral Vascular Disease: A Systematic Review. AB - High mortality rates have been reported after major amputations of a lower limb secondary to diabetes and peripheral vascular disease. However, the mortality rates have varied across studies. A systematic review of the 5-year mortality after nontraumatic major amputations of the lower extremity was conducted. A data search was performed of Medline using OVID, CINHAL, and Cochrane, 365 abstracts were screened, and 79 full text articles were assessed for eligibility. After review, 31 studies met the inclusion and exclusion criteria. Overall, the 5-year mortality rate was very high among patients with any amputation (major and minor combined), ranging from 53% to 100%, and in patients with major amputations, ranging from 52% to 80%. Mortality after below-the-knee amputation ranged from 40% to 82% and after above-the-knee amputation from 40% to 90%. The risk factors for increased mortality included age, renal disease, proximal amputation, and peripheral vascular disease. Although our previous systematic review of the 5 year mortality after ulceration had much lower rates of death, additional studies are warranted to determine whether amputation hastens death or is a marker for underlying disease severity. PMID- 26898399 TI - Ice stream motion facilitated by a shallow-deforming and accreting bed. AB - Ice streams drain large portions of ice sheets and play a fundamental role in governing their response to atmospheric and oceanic forcing, with implications for sea-level change. The mechanisms that generate ice stream flow remain elusive. Basal sliding and/or bed deformation have been hypothesized, but ice stream beds are largely inaccessible. Here we present a comprehensive, multi scale study of the internal structure of mega-scale glacial lineations (MSGLs) formed at the bed of a palaeo ice stream. Analyses were undertaken at macro- and microscales, using multiple techniques including X-ray tomography, thin sections and ground penetrating radar (GPR) acquisitions. Results reveal homogeneity in stratigraphy, kinematics, granulometry and petrography. The consistency of the physical and geological properties demonstrates a continuously accreting, shallow deforming, bed and invariant basal conditions. This implies that ice stream basal motion on soft sediment beds during MSGL formation is accommodated by plastic deformation, facilitated by continuous sediment supply and an inefficient drainage system. PMID- 26898401 TI - Was access to health care easy for immigrants in Spain? The perspectives of health personnel in Catalonia and Andalusia. AB - Until April 2012, all Spanish citizens were entitled to health care and policies had been developed at national and regional level to remove potential barriers of access, however, evidence suggested problems of access for immigrants. In order to identify factors affecting immigrants' access to health care, we conducted a qualitative study based on individual interviews with healthcare managers (n=27) and professionals (n=65) in Catalonia and Andalusia, before the policy change that restricted access for some groups. A thematic analysis was carried out. Health professionals considered access to health care "easy" for immigrants and similar to access for autochthons in both regions. Clear barriers were identified to enter the health system (in obtaining the health card) and in using services, indicating a mismatch between the characteristics of services and those of immigrants. Results did not differ among regions, except for in Catalonia, where access to care was considered harder for users without a health card, due to the fees charged, and in general, because of the distance to primary health care in rural areas. In conclusion, despite the universal coverage granted by the Spanish healthcare system and developed health policies, a number of barriers in access emerged that would require implementing the existing policies. However, the measures taken in the context of the economic crisis are pointing in the opposite direction, towards maintaining or increasing barriers. PMID- 26898400 TI - Parallel expression profiling of hepatic and serum microRNA-122 associated with clinical features and treatment responses in chronic hepatitis C patients. AB - MicroRNAs (miRNAs) are small, non-coding RNAs that regulate a variety of biological processes. Recently, human liver-specific miRNA miR-122 has been reported to facilitate hepatitis C virus (HCV) replication in liver cells. HCV is one of the leading causes of liver diseases worldwide. In Pakistan, the estimated prevalence is up to 10%. Here, we report hepatic and serum miR-122 expression profiling from paired liver and serum samples from treatment-naive chronic hepatitis C (CHC) patients and controls. We aimed to elucidate the biomarker potential of serum miR-122 for monitoring disease progression and predicting end treatment response (ETR). Hepatic miR-122 levels were significantly down regulated in CHC patients. A significant inverse correlation was observed between hepatic and serum miR-122 levels, indicating that serum miR-122 levels reflect HCV-associated disease progression. Both hepatic and serum miR-122 were significantly correlated (P < 0.05) with several clinicopathological features of CHC. Receiver operator curve analysis showed that serum miR-122 had superior discriminatory ability even in patients with normal alanine transaminase levels. Multivariate logistic regression analysis highlighted pre-treatment serum miR-122 levels as independent predictors of ETR. In conclusion, serum miR-122 holds the potential to serve as a promising biomarker of disease progression and ETR in CHC patients. PMID- 26898404 TI - Fundamentals of Orthodontic Treatment Mechanics. PMID- 26898403 TI - Nucleotides protect rat brain astrocytes against hydrogen peroxide toxicity and induce antioxidant defense via P2Y receptors. AB - Consequences of neurodegenerative diseases or stroke also depend on astroglial survival during oxidative stress. P2Y receptors that are widely distributed in the central nervous system are suggested to be involved in cytoprotection. However, knowledge about the efficacy of protection by P2Y receptors and their involvement in antioxidant protective pathways is scarce. Here, we investigate the viability and reactive oxygen species (ROS) production after exposure of rat astrocytes to hydrogen peroxide. We determined the influence of treatment with the P2Y1 receptor-specific agonist 2-methyl-thio-ADP (2MeSADP) and the broad range P2Y receptor agonist adenosine 5'-(3-thiotriphosphate) (ATPgammaS). Preincubation (24-h before hydrogen peroxide application) and incubation with ATPgammaS and 2MeSADP protected astrocytes. The ROS production in hydrogen peroxide-treated astrocytes was reduced by pre- and co-incubation with ATPgammaS or 2MeSADP. Changes of levels of expression of antioxidant defense systems in astrocytes by treatment with P2Y receptor agonists were analyzed. Incubation with ATPgammaS and 2MeSADP increased mRNA levels of CAT encoding catalase and SOD2, encoding mitochondrial manganese dependent superoxide dismutase. ATPgammaS additionally increased mRNA levels of SOD3, encoding extracellular superoxide dismutase (ECSOD). Levels of total glutathione (GSH) increased in ATPgammaS/2MeSADP-treated astrocytes. mRNA levels of genes involved in GSH synthesis and in import of GSH precursors were analyzed after treatment with ATPgammaS and 2MeSADP. Both agonists significantly increased mRNA levels of a subunit of glutamate cysteine ligase, and a subunit of antiporter system xc(-). Changes in mRNA levels of antioxidant enzymes and genes of GSH metabolism depend on rise of intracellular Ca(2+) by P2Y receptor and basal activity of protein kinase A (PKA). SOD3 induction is suggested to depend on increased intracellular Ca(2+), increased cyclic AMP levels and PKA activity. Thus, we confirm a role of purinergic signaling in astrocytic survival during oxidative stress by maintaining antioxidant defense, highlighting P2Y receptors as potential targets for cytoprotection. PMID- 26898402 TI - Human cytomegalovirus UL49 encodes an early, virion-associated protein essential for virus growth in human foreskin fibroblasts. AB - Despite recent results of deletion experiments showing that open reading frame (ORF) UL49 of human cytomegalovirus (HCMV) is essential, the expression, function and functional location of its encoded protein remain unknown. We generated an antibody specific for pUL49 to investigate the protein product encoded by the UL49 ORF and identified its function in HCMV-infected host foreskin fibroblasts. A bacterial artificial chromosome (BAC) of HCMV strain Towne (pRV-Towne) and the UL49-deleted mutant pRV-delUL49Towne were used to observe virus growth by plaque assay. Using a UL49-protein-binding antibody, we located pUL49 in the fibroblast cytoplasm. pUL49 exhibited expression kinetics resembling those of the class beta 2 proteins and was detected in the virion tegument. Following deletion of UL49 ORF, the virus failed to replicate, but it could be recovered by addition of pUL49 from pCDNA3.1 (+)-UL49. Our findings indicate that UL49 ORF is essential for HCMV replication in host foreskin fibroblasts. PMID- 26898406 TI - Women, Physical Activity, and Quality of Life: Self-concept as a Mediator. AB - The objectives of this research are: (a) analyze the incremental validity of physical activity's (PA) influence on perceived quality of life (PQL); (b) determine if PA's predictive power is mediated by self-concept; and (c) study if results vary according to a unidimensional or multidimensional approach to self concept measurement. The sample comprised 160 women from Burgos, Spain aged 18 to 45 years old. Non-probability sampling was used. Two three-step hierarchical regression analyses were applied to forecast PQL. The hedonic quality-of-life indicators, self-concept, self-esteem, and PA were included as independent variables. The first regression analysis included global self-concept as predictor variable, while the second included its five dimensions. Two mediation analyses were conducted to see if PA's ability to predict PQL was mediated by global and physical self-concept. Results from the first regression shows that self-concept, satisfaction with life, and PA were significant predictors. PA slightly but significantly increased explained variance in PQL (2.1%). In the second regression, substituting global self-concept with its five constituent factors, only the physical dimension and satisfaction with life predicted PQL, while PA ceased to be a significant predictor. Mediation analysis revealed that only physical self-concept mediates the relationship between PA and PQL (z = 1.97, p < .050), and not global self-concept. Physical self-concept was the strongest predictor and approximately 32.45 % of PA's effect on PQL was mediated by it. This study's findings support a multidimensional view of self-concept, and represent a more accurate image of the relationship between PQL, PA, and self concept. PMID- 26898405 TI - Myo-Inositol Supplementation to Prevent Gestational Diabetes Mellitus. AB - Gestational diabetes mellitus (GDM) is a common complication characterized by increased insulin resistance, and by increased risk for adverse pregnancy outcomes affecting both the mother and the fetus. International guidelines describe optimal ways to recognize it, and the recommended treatment of patients affected to reduce adverse outcomes. Improving insulin resistance could reduce incidence of GDM and its complications. Recently, a few trials have been published on the possible prevention of GDM. Inositol has been proposed as a food supplement that might reduce gestational diabetes incidence in high-risk pregnant women. PMID- 26898407 TI - Burden of Coronary Heart Disease Rehospitalizations Following Acute Myocardial Infarction in Older Adults. AB - PURPOSE: Studies of prognosis following acute myocardial infarction (AMI) conventionally examine the first recurrent coronary heart disease (CHD) event which may not adequately characterize the full burden of CHD hospitalizations. We therefore examined the cumulative number of CHD rehospitalizations following AMI among older adults in the United States. METHODS: We conducted a retrospective cohort study of 78,085 Medicare beneficiaries aged >=66 years without recent CHD history who were hospitalized for AMI in 2000-2010. Counts of CHD rehospitalizations over a maximum of 10 years of follow-up were calculated. Characteristics were assessed through claims and enrollment information and associations with CHD rehospitalizations were evaluated using Poisson models. RESULTS: Over 25 % of beneficiaries were aged >=85 years, 55 % were women, and 89 % were white. Comorbidities were common, including diabetes (22.9 %), hypertension (46.7 %), heart failure (10.3 %), and chronic obstructive pulmonary disease (19.2 %). Following AMI, 16,078 beneficiaries (20.6 %) were hospitalized for CHD a total of 23,132 times. Among those who experienced at least one CHD rehospitalization, 35.9 % had >=2 CHD rehospitalizations (n = 5773, 7.4 % of all beneficiaries with AMI) in the ensuing decade. Associations of demographics, comorbidities, and index hospitalization characteristics with rates of first and total CHD rehospitalizations were largely similar. Age >=85 years versus 66-69 years was more strongly associated with first (rate ratio [RR] 1.43) than total (RR 1.35) CHD rehospitalization (p < 0.05), as was male versus female sex (RR 1.13 and 1.07). CONCLUSIONS: Emphasizing the first recurrent CHD rehospitalization underestimates the burden of disease experienced among older adults with AMI. PMID- 26898408 TI - Propensity of salicylamide and ethenzamide cocrystallization with aromatic carboxylic acids. AB - The cocrystallization of salicylamide (2-hydroxybenzamide, SMD) and ethenzamide (2-ethoxybenzamide, EMD) with aromatic carboxylic acids was examined both experimentally and theoretically. The supramolecular synthesis taking advantage of the droplet evaporative crystallization (DEC) technique was combined with powder diffraction and vibrational spectroscopy as the analytical tools. This led to identification of eleven new cocrystals including pharmaceutically relevant coformers such as mono- and dihydroxybenzoic acids. The cocrystallization abilities of SMD and EMD with aromatic carboxylic acids were found to be unexpectedly divers despite high formal similarities of these two benzamides and ability of the R2,2(8) heterosynthon formation. The source of diversities of the cocrystallization landscapes is the difference in the stabilization of possible conformers by adopting alternative intramolecular hydrogen boding patterns. The stronger intramolecular hydrogen bonding the weaker affinity toward intermolecular complexation potential. The substituent effects on R2,2(8) heterosynthon properties are also discussed. PMID- 26898410 TI - The impact of Primary Ciliary Dyskinesia on the upper respiratory tract. AB - Primary Ciliary Dyskinesia (PCD) is an autosomal recessive genetic condition affecting the function of motile cilia. The upper respiratory tract is lined with ciliated epithelium and hence a hallmark of PCD is the development, from the neonatal period onwards, of persisting secretion retention and suppurative infection in the middle ear, nose and facial sinuses [1]. This review aims to remind the clinician involved in the care of a patient with PCD of the complexities of making the diagnosis of chronic rhinosinusitis (CRS) and chronic otitis media with effusion (ChOME), the morbidity associated with CRS and ChOME and of current evidence of best practice for the management of these conditions. PMID- 26898409 TI - Unraveling and engineering the production of 23,24-bisnorcholenic steroids in sterol metabolism. AB - The catabolism of sterols in mycobacteria is highly important due to its close relevance in the pathogenesis of pathogenic strains and the biotechnological applications of nonpathogenic strains for steroid synthesis. However, some key metabolic steps remain unknown. In this study, the hsd4A gene from Mycobacterium neoaurum ATCC 25795 was investigated. The encoded protein, Hsd4A, was characterized as a dual-function enzyme, with both 17beta-hydroxysteroid dehydrogenase and beta-hydroxyacyl-CoA dehydrogenase activities in vitro. Using a kshAs-null strain of M. neoaurum ATCC 25795 (NwIB-XII) as a model, Hsd4A was further confirmed to exert dual-function in sterol catabolism in vivo. The deletion of hsd4A in NwIB-XII resulted in the production of 23,24-bisnorcholenic steroids (HBCs), indicating that hsd4A plays a key role in sterol side-chain degradation. Therefore, two competing pathways, the AD and HBC pathways, were proposed for the side-chain degradation. The proposed HBC pathway has great value in illustrating the production mechanism of HBCs in sterol catabolism and in developing HBCs producing strains for industrial application via metabolic engineering. Through the combined modification of hsd4A and other genes, three HBCs producing strains were constructed that resulted in promising productivities of 0.127, 0.109 and 0.074 g/l/h, respectively. PMID- 26898411 TI - Public awareness and self-efficacy of cardiopulmonary resuscitation in communities and outcomes of out-of-hospital cardiac arrest: A multi-level analysis. AB - BACKGROUND: This study aims to test the association between capacity of cardiopulmonary resuscitation (CPR) at community level and survival after out-of hospital cardiac arrest (OHCA). METHODS: Emergency medical service (EMS)-treated OHCAs with cardiac etiology in Korea between 2012 and 2013 were analyzed, excluding cases witnessed by EMS providers. Exposure variables were five indexes of community CPR capacity: awareness of CPR (CPR-Awareness), any training experience of CPR (CPR-Any-Training), recent CPR training within the last 2 years (CPR-Recent-Training), CPR training with a manikin (CPR-Manikin-Training), and CPR self-efficacy (CPR-Self-Efficacy). All measures of capacity were calculated as aggregated values for each county level using the national Korean Community Health Survey database of 228,921 responders sampled representatively from 253 counties in 2012. Endpoints were bystander CPR (BCPR) and survival to discharge. We calculated adjusted odds ratios (AORs) per 10% increment in community CPR capacity using multi-level logistic regression models, adjusting for potential confounders at individual levels. RESULTS: Of 29,052 eligible OHCAs, 11,079 (38.1%) received BCPR. Patients were more likely to receive BCPR in communities with higher proportions of residents with CPR-Awareness, CPR-Any-Training, CPR Recent-Training, CPR-Manikin-Training, and CPR-Self-Efficacy (all p<0.01). AORs for BCPR were 1.06 (1.03-1.10) per 10% increment in CPR-Awareness, 1.10 (1.04 1.15) for CPR-Any-Training, and 1.08 (1.03-1.13) for CPR-Self-Efficacy. For survival to discharge, AORs (95% CIs) were 1.34 (1.23-1.47) per 10% increment in CPR-Awareness, 1.36 (1.20-1.54) for CPR-Any-Training, and 1.29 (1.15-1.45) for CPR-Self-Efficacy. CONCLUSION: Higher CPR capacity at community level was associated with higher bystander CPR and survival to discharge rates after OHCA. PMID- 26898413 TI - Use of telephone CPR advice in Ireland: Uptake by callers and delays in the assessment process. AB - INTRODUCTION: Telephone CPR (T-CPR) has significant variations in time from call receipt to first compression, with reported delays of up to five minutes. Ireland's National Ambulance Service (NAS) uses T-CPR based on standard AMPDS questions; we aimed to identify the time to first compression and the times needed for question blocks. Ireland has a low survival rate from out-of-hospital cardiac arrest, (6% in 2013). METHODS: A retrospective review of all cardiac arrests in a two-year period was carried out in one NAS region. All cardiac arrests were identified from the national registry and audio tapes and Patient Care Reports reviewed, together with survival data. Times from call handover were noted and categorised in terms of the key question items. RESULTS: 202 cardiac arrests occurred in the period (36/10(5)/year); 30 (14.9%) patients were not in cardiac arrest at the time of the call. Records were available for 145/172 patients in cardiac arrest at the time of the call. In 63/145 (43.4%) cases, the caller was not at the patient's side. Of the remaining 82 cases, in 13/82 (15.8%) CPR was underway (two survivors), in 22/82 (26.8%) the caller would not attempt T CPR (one survivor); in 47/82 (57.3%), T-CPR was carried out (two survivors). Median time to first compression was 05:28min (range 03:18-10:29). Repeated questioning in relation to the patient's condition caused most of the delays. CONCLUSIONS: Many callers are willing to attempt T-CPR but the questioning/instruction process causes significant delays. A focused, brief questioning process is required. PMID- 26898412 TI - The value of vital sign trends for detecting clinical deterioration on the wards. AB - AIM: Early detection of clinical deterioration on the wards may improve outcomes, and most early warning scores only utilize a patient's current vital signs. The added value of vital sign trends over time is poorly characterized. We investigated whether adding trends improves accuracy and which methods are optimal for modelling trends. METHODS: Patients admitted to five hospitals over a five-year period were included in this observational cohort study, with 60% of the data used for model derivation and 40% for validation. Vital signs were utilized to predict the combined outcome of cardiac arrest, intensive care unit transfer, and death. The accuracy of models utilizing both the current value and different trend methods were compared using the area under the receiver operating characteristic curve (AUC). RESULTS: A total of 269,999 patient admissions were included, which resulted in 16,452 outcomes. Overall, trends increased accuracy compared to a model containing only current vital signs (AUC 0.78 vs. 0.74; p<0.001). The methods that resulted in the greatest average increase in accuracy were the vital sign slope (AUC improvement 0.013) and minimum value (AUC improvement 0.012), while the change from the previous value resulted in an average worsening of the AUC (change in AUC -0.002). The AUC increased most for systolic blood pressure when trends were added (AUC improvement 0.05). CONCLUSION: Vital sign trends increased the accuracy of models designed to detect critical illness on the wards. Our findings have important implications for clinicians at the bedside and for the development of early warning scores. PMID- 26898414 TI - N-3 polyunsaturated fatty acid DHA during IVM affected oocyte developmental competence in cattle. AB - The positive effect of n-3 polyunsaturated fatty acids (FAs) on fertility in ruminants seems to be partly mediated through direct effects on the oocyte developmental potential. We aimed to investigate whether supplementation with physiological levels of docosahexaenoic acid (DHA, C22:6 n-3 polyunsaturated fatty acids) during IVM has an effect on oocyte maturation and in vitro embryo development in cattle. We reported that DHA (0, 1, 10, or 100 MUM) had no effect on oocyte viability or maturation rate after 22-hour IVM. Incubation of oocyte cumulus complexes with 1-MUM DHA during IVM significantly increased (P < 0.05) oocyte cleavage rate as compared with control (86.1% vs. 78.8%, respectively) and the greater than 4-cell embryo rate at Day 2 after parthenogenetic activation (39.1% vs. 29.7%, respectively). Supplementation with 1 MUM DHA during IVM also induced a significant increase in the blastocyst rate at Day 7 after IVF as compared with control (30.6% vs. 17.6%, respectively) and tended to increase the number of cells in the blastocysts (97.1 +/- 4.9 vs. 81.2 +/- 5.3, respectively; P = 0.08). On the contrary, 10-MUM DHA had no effects, whereas 100-MUM DHA significantly decreased the cleavage rate compared with control (69.5% vs.78.8%, respectively) and the greater than 4-cell embryo rate at Day 2 after parthenogenetic activation (19.5% vs. 29.7%). As was shown by real-time polymerase chain reaction, negative effects of 100-MUM DHA were associated with significant increase of progesterone synthesis by oocyte-cumulus complexes, a three-fold increase in expression level of FA transporter CD36 and a two-fold decrease of FA synthase FASN genes in cumulus cells (CCs) of corresponding oocytes. Docosahexaenoic acid at 1 and 10 MUM had no effect on expression of those and other key lipid metabolism-related genes in CC. In conclusion, administration of a low physiological dose of DHA (1 MUM) during IVM may have beneficial effects on oocyte developmental competence in vitro without affecting lipid metabolism gene expression in surrounding CCs, contrarily to 100 MUM DHA which diminished oocyte quality associated with perturbation of lipid and steroid metabolism in CC. PMID- 26898415 TI - The physiological expression of scavenger receptor SR-B1 in canine endometrial and placental epithelial cells and its potential involvement in pathogenesis of pyometra. AB - Pyometra, the purulent inflammation of the uterus, is a common uterine disease of bitches that has potentially life-threatening consequences. The opportunistic bacterial infection of the uterus often progresses into the serious systemic inflammatory response syndrome. In a previous study, we characterized epithelial foam cells in the canine endometrial surface occurring in metestrus, and we regularly observed pronounced epithelial foam-cell formations in pyometra affected uteri. Therefore, it was assumed that the mechanism behind lipid droplet accumulation in surface epithelial cells might even increase bacterial binding capacity and promote pyometra development. Lipid droplet accumulation in epithelial cells is accomplished via specialized lipid receptors called scavenger receptors (SR). Scavenger receptor class B type 1 (SR-B1) is an important receptor for lipid accumulation in diverse cell types, but it is also a strong binding partner for bacteria, and thereby enhances bacterial adhesion and clinical signs of systemic inflammatory response syndrome. In the present study, after the isolation of metestrous surface epithelial cells from canine uteri by laser capture microdissection, SR-B1 was identified at the messenger RNA (mRNA) level by quantitative real time polymerase chain reaction and also at the protein level by means of immunohistochemistry. In pyometra-affected uteri, SR-B1 mRNA expression was higher than that in the healthy control samples, and SR-B1 protein was expressed in the surface and crypt epithelial cells. Furthermore, to understand the physiological role of SR-B1 expression in the metestrus surface epithelial cells, we investigated its expression in the epithelial cells of the glandular chambers of canine placenta in different stages of gestation because these cells are also characterized by lipid droplet accumulation. SR-B1 was present in the placental epithelial cells of the glandular chambers from 25 to 30 and 45 to 50 days of gestation, where basal and basal and/or apical expression patterns were observed. The physiological expression of SR-B1 in metestrous endometrial surface epithelia might be related to the implantation process and embryo development, as SR-B1 was also identified in the epithelial cells of the canine placental chambers. The increased levels of SR-B1 in pyometra-affected uteri indicate a potential role for this scavenger receptor in endometrial bacterial adhesion. PMID- 26898416 TI - Molecular dynamics study of wetting behavior of grafted thermo-responsive PNIPAAm brushes. AB - In this work, the effect of temperature on the contact angle of a water droplet on grafted thermo-responsive poly-(N-isopropylacrylamide) (PNIPAAm) polymer brushes is studied using all-atom molecular dynamics simulations in the temperature range of 270-330 K. A shift from 55 degrees to 65 degrees in contact angle values is observed as the temperature increases from 300 K to 310 K, which is in line with the experimental reports. The behavior of a water droplet on PNIPAAm brushes is analyzed using hydrogen bond analysis, water diffusion, radial distribution functions, the potential of mean force, excess entropy and the second virial coefficient (B2). The thermo-responsive behavior of PNIPAAm brushes, quantified using the excess entropy and B2 of PNIPAAm-water and water-water interactions, is mainly governed by polymer-water interactions. In particular, the excess entropy and B2 of PNIPAAm resulting from the PNIPAAm-water interactions are found to increase with increasing temperature. The dehydration of PNIPAAm brushes and the increase in the contact angle of water were confirmed to be entropy driven processes. PMID- 26898417 TI - Translating formative research findings into a behaviour change strategy to promote antenatal calcium and iron and folic acid supplementation in western Kenya. AB - The World Health Organization now recommends integrating calcium supplements into antenatal micronutrient supplementation programmes to prevent pre-eclampsia, a leading cause of maternal mortality. As countries consider integrating calcium supplementation into antenatal care (ANC), it is important to identify context specific barriers and facilitators to delivery and adherence. Such insights can be gained from women's and health workers' experiences with iron and folic acid (IFA) supplements. We conducted in-depth interviews with 22 pregnant and post partum women and 20 community-based and facility-based health workers in Kenya to inform a calcium and IFA supplementation programme. Interviews assessed awareness of anaemia, pre-eclampsia and eclampsia; ANC attendance; and barriers and facilitators to IFA supplement delivery and adherence. We analyzed interviews inductively using the constant comparative method. Women and health workers identified poor diet quality in pregnancy as a major health concern. Neither women nor health workers identified pre-eclampsia, eclampsia, anaemia or related symptoms as serious health threats. Women and community-based health workers were unfamiliar with pre-eclampsia and eclampsia and considered anaemia symptoms normal. Most women had not received IFA supplements, and those who had received insufficient amounts and little information about supplement benefits. We then developed a multi-level (health facility, community, household and individual) behaviour change strategy to promote antenatal calcium and IFA supplementation. Formative research is an essential first step in guiding implementation of antenatal calcium supplementation programmes to reduce pre-eclampsia. Because evidence on how to implement successful calcium supplementation programmes is limited, experiences with antenatal IFA supplementation can be used to guide programme development. PMID- 26898418 TI - Inhibitory effects of shRNA on expression of JNK1 and migration and invasion in mouse hepatocellular carcinoma cell lines mediated by ultrasound-targeted microbubble destruction. AB - AIM: The inhibitory effects on expression of JNK1 in mouse hepatocellular carcinoma cell lines and cell migration and invasion were mediated by ultrasound targeted microbubble destruction (UTMD). MATERIALS AND METHODS: The best shRNA vector was built and screened. The hepatocellular carcinoma cell lines were cultured in vitro and divided into five groups: the group of normal Hca-F cells, the group of shRNA plasmid (already selected from the above procedure), the group of Lipofectamine, the group of UTMD (ultrasound microbubbles combined with ultrasound exposure) and the group of Lipofectamine and UTMD. The transfection rate was observed by inverted fluorescence microscope. The expression levels of JNK1 mRNA and protein were evaluated by fluorescence quantitative PCR and Western Blot respectively. The cell proliferation was detected by CCK-8. The ability of migration and invasion in vitro was detected by transwell assay. RESULTS: The best shRNA vector was established. The comparison of the transfection rate: The group of Lipofectamine and UTMD was larger than that of the groups of shRNA plasmid, Lipofectamine lipofection and UTMD (all P<0.05). There was no significant difference between the group of Lipofectamine and the group of UTMD (P>0.05). The comparison of the expression levels of JNK1 mRNA and protein: Both of the mRNA and protein expression levels were lowest in the group of Lipofectamine and UTMD (all P<0.05). CCK-8 showed that cell viability decreased most in the group of Lipofectamine and UTMD (all P<0.05); Transwell assay showed that the abilities of migration and invasion decreased most in the group of Lipofectamine and UTMD (all P<0.05). CONCLUSION: The transfection rate of JNK1 shRNA can be improved through the combination of lipofection and UTMD in mouse hepatocellular carcinoma cell lines, therefore enhancing the inhibitory effects of gene expression. The inhibitory effects of cell proliferation, migration and invasion can also be enhanced. PMID- 26898419 TI - The chemokine CXCL9 expression is associated with better prognosis for colorectal carcinoma patients. AB - The chemokine CXCL9 has been demonstrated to play an important role in the development of human malignancies. However, its prognostic significance in cancer patients remains unclear and less is known about its role in colonrectal carcinoma (CRC) patients. In this study, we found that the relative mRNA expression level of CXCL9 in primary colorectal tumor tissues was significantly higher than that in corresponding normal colon tissues. CXCL9 protein expression was also detected in 102 of 130 primary CRC patients by immunochemistry. Thus, CXCL9 might play a vital role in the progression of colorectal cancer. By analyzing the correlation between clinicopathological factors of patients and expression of CXCL9 protein, we showed that the expression of CXCL9 was significantly associated with tumor differentiation, tumor invasion, lymph node metastasis, distant metastasis, and vascular invasion, but not with other factors of CRC patients including age, gender, tumor location and tumor size. Furthermore, by performing Kaplan-Meier method as well as Cox's univariate and multivariate hazard regression model, we found that the higher the CXCL9 expression, the higher overall survival rate was observed, and CXCL9 expression was a significant independent prognostic factor for CRC patients. Therefore, CXCL9 is a useful predictor of better clinical outcome in CRC patients. PMID- 26898420 TI - Preparation and pharmaceutical evaluation of acetaminophen nano-fiber tablets: Application of a solvent-based electrospinning method for tableting. AB - In this study, we developed nano-fiber-based tablets with acetaminophen (AAP; LogPow=0.51) for controlled-release delivery systems and evaluated in vitro drug dissolution and in vivo pharmacokinetics in rats. Nano-fibers made from methacrylic acid copolymer S (MAC; EUDRAGIT S100) and containing AAP were prepared using a solvent-based electrospinning (ES) method. In vitro dissolution rate profiles of AAP showed tableting pressure-dependent decreases and pH dependent increases. The results of tablet tracking by X-ray irradiation showed tablets based on MAC nano-fibers did not disintegrate in the upper intestinal lumen and had the properties of a long-term-acting tablet. In addition, the in vitro release profiles of AAP from nano-fiber tablets prepared by dissolving MAC with AAP (NFT), nano-fiber tablets prepared by adsorbing AAP to drug-free MAC nano-fibers (NFTadso), and tablets prepared by adsorbing half the amount of AAP to MAC nano-fibers containing the remaining amount of AAP (NFThalf) showed independent controlled-release aspects of AAP compared with physical mixture tablets (PMT). In vivo pharmacokinetic studies in rats after intraduodenal administration of 14 mg/rat AAP in NFT, NFTadso, and NFThalf demonstrated that all these tablets based on MAC nano-fibers showed sustained-release profiles compared with PMT, and showed ultra-sustained release properties for AAP. These new tablets based on MAC nano-fibers did not disintegrate in the intestine in the lower pH region, and the tablets could regulate the release of AAP in a pH dependent manner. The ES method is a useful technique to prepare nano-fibers and showed promising results as an oral delivery system for sustained-release regulation. PMID- 26898421 TI - Statins inhibited the MIP-1alpha expression via inhibition of Ras/ERK and Ras/Akt pathways in myeloma cells. AB - Macrophage inflammatory protein-1alpha (MIP-1alpha) is detected at high concentrations in patients with multiple myeloma. It is thought to play an important role in the etiology of multiple myeloma and osteolysis. Thus, inhibiting MIP-1alpha expression may be useful in developing therapeutic treatments for multiple myeloma-induced osteolysis. In this study, we investigated the potential of statins to inhibit mRNA expression and secretion of MIP-1alpha in mouse myeloma cells (MOPC-31C). We found that statins inhibited the lipopolysaccharide (LPS)-induced MIP-1alpha mRNA expression and protein secretion in MOPC-31C cells. This inhibition was reversed when farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP), intermediates of the mevalonate pathway, were combined with statins. Furthermore, statins reduced the GTP form of Ras, a phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2), and phosphorylated Akt. Our results indicate that statins inhibit biosynthesis of FPP and GGPP and thereby down regulate signal transduction of Ras/ERK and Ras/Akt pathways. The net effect suppresses LPS-induced MIP-1alpha mRNA expression and protein secretion in MOPC-31C cells. Thus, statins hold great promise for developing effective therapies against myeloma-induced osteolysis. PMID- 26898422 TI - Heme oxygenase-1 contributes to imatinib resistance by promoting autophagy in chronic myeloid leukemia through disrupting the mTOR signaling pathway. AB - Heme oxygenase-1 (HO-1) has been verified to play an important role in imatinib (IM)-resistant chronic myeloid leukemia (CML) cells, but the mechanism remains unclear. In drug resistant CML cells, HO-1 expression abnormally increased and that of autophagy-related protein LC-3I/II also increased, so we herein postulated HO-1 was associated with autophagy. HO-1 expressions in IM sensitive/resistant K562/K562R cells were regulated through lentiviral mediation. K562 cells transfected with HO-1 resisted IM and underwent obvious autophagy. After HO-1 expression was silenced in K562R cells, autophagy was inhibited and the sensitivity to IM was increased. The findings were related with the inhibitory effects of high HO-1 expression on the mTOR signaling pathway that negatively regulated autophagy. High HO-1 expression promoted autophagy by inhibiting mTOR. Similar to the cell line results, mononuclear cells of IM resistant CML patients became significantly sensitive to IM when HO-1 expression was inhibited. In summary, HO-1, which is involved in the development of chemoresistance in leukemia cells by regulating autophagy, may be a novel target for improving leukemia therapy. PMID- 26898423 TI - The influence of common free radicals and antioxidants on development of Alzheimer's Disease. AB - Alzheimer's Disease (AD) is one of the most important neurodegenerative disorders in the 21st century for the continually aging population. Despite an increasing number of patients, there are only few drugs to treat the disease. Numerous studies have shown several causes of the disorder, one of the most important being oxidative stress. Oxidative stress is connected with a disturbance between the levels of free radicals and antioxidants in organisms. Solutions to this problem are antioxidants, which counteract the negative impact of the reactive molecules. Unfortunately, the currently available drugs against AD do not exhibit activity toward these structures. Due to the fact that natural substances are extremely significant in new drug development, numerous studies are focused on substances which exhibit a few activities including antioxidants and other anti AD behaviors. This review article presents the most important studies connected with the influence of free radicals on development of AD and antioxidants as potential drugs toward AD. PMID- 26898424 TI - Protective role of epigallocatechin-3-gallate in health and disease: A perspective. AB - Tea is the most popular beverages all over the world. Polyphenols are found ubiquitously in tea leaves and their regular consumption has been associated with a reduced risk of a number of chronic diseases including cancer, cardiovascular and neurodegenerative diseases. Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenol in tea leaves and received great attention due to their protective role in the prevention of the diseases. Rather than eliciting direct antioxidant effects, the mechanisms by which tea polyphenol express these beneficial properties appear to involve their interaction with cellular signaling pathways and related machinery that mediate cell function under both normal and pathological conditions. The central focus of this review is to provide an overview of the role that the major tea polyphenol, EGCG plays in preventing cancer, cardiovascular and neurodegenerative diseases. This review present epidemiological data, human intervention study findings, as well as animal and in vitro studies in support of these actions and delineates the molecular mechanism associated with the action of EGCG in ameliorating of such diseases. PMID- 26898425 TI - Possible involvement of L-arginine-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signaling pathway in the antidepressant-like effect of Wuling mycelia powder in rat. AB - CONTEXT: Wuling mycelia powder is the dry powder of rare a fungi Xyla ria sp., Carbon species, with a long history of medicinal use in Chinese medicine. Recently it has shown a powerful antidepressant activity in clinic. OBJECTIVE: The present study explores the antidepressant activity of Wuling mycelia powder in chronic unpredictable mild stress (CUMS) rats and its possible involvement of l-arginine-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signaling pathway. MATERIALS AND METHODS: Experiments were performed in the rat CUMS model. CUMS rats were treated with Wuling mycelia powder (0.5, 1.0 or 2.0 g/kg, i.g.) to test behavioral changes including the sucrose preference, the crossing number and food consumption. Further, L-arginine (substrate for nitric oxide) (750 mg/kg), 7 nitroindazole (a specific neuronal nitric oxide synthase inhibitor) (25 mg/kg), sildenafil (phosphodiesterase 5 inhibitor) (5 mg/kg) and methylene blue (direct inhibitor of both nitric oxide synthase and soluble guanylate cyclase) (10 mg/kg) were treated for 60 min before each test to detect the possible mechanism of antidepressant-like effect of Wuling mycelia powder. RESULTS: After 4 weeks of administration, both 1.0 or 2.0 g/kg Wuling mycelia powder suppressed the behavioral changes including the sucrose preference [F(3, 31)=50.87, p<0.001], the crossing number [F(3, 31)=68.98, p<0.05], and food consumption [F(3, 31)=19.04, p<0.05] in the CUMS rats. The antidepressant-like effect of Wuling mycelia powder was prevented by pretreatment with l-arginine and sildenafil. Pretreatment of rats with 7-nitroindazole and methylene blue potentiated the effect of Wulin mycelia powder. DISCUSSION AND CONCLUSION: Our findings demonstrate that Wuling mycelia powder has an antidepressant-like effect in the CUMS rats, and possible involvement of L-arginine-nitric oxide-cyclic GMP signaling pathway in its antidepressant effect. PMID- 26898426 TI - Selection of reliable reference genes in eutopic and ectopic endometrium for quantitative expression studies. AB - PURPOSE: Physiological changes during menstrual cycle cause the endometrium and endometriosis to develop specific kind of tissues, especially in regard to the gene expression profiles, which may include also housekeeping genes, commonly used as reference genes (RGs) in quantitative studies. Reverse transcription, followed by quantitative polymerase chain reaction (RT-qPCR) is the most precise and commonly used method in gene expression studies. In order to reduce effects of technical approaches and biological variability of gene's expression level, the studies often employ RGs in experimental data normalization. However, the expression of RGs is not always stable and depends on several variables. Thus, the selection of appropriate RG is one of the most significant steps to obtain reliable results in RT-qPCR-based methods. MATERIAL AND METHODS: With the usage of RT-qPCR, we researched the expression of seven genes (ACTB, B2M, G6PD, GAPD, GUSB, HPRT and PPIA) as reliable reference genes in eutopic and ectopic endometrial tissue specimens obtained during standard surgery of women of reproductive age. Stability of expression level was analyzed by the most universal MS Excel plug-ins including: geNorm, NormFinder and BestKeeper. The descriptive statistics were evaluated using Statistica software. RESULTS: The distribution of threshold (Ct) values was not equal. We identified genes with higher expression level (referring to Ct values) such as ACTB and B2M, medium e.g., GAPD and low expression level, e.g., G6PD and HPRT. We demonstrated that the stability of the analyzed reference genes was not homogenous, and different algorithms pointed to PPIA, GAPD and B2M as the most stable ones in eutopic and ectopic endometrium. On the contrary to these, GUSB and G6PD were the most unstable ones. CONCLUSIONS: In RT-qPCR-based analyses of gene expression level in eutopic and ectopic endometrium, we strongly recommend that a minimum of two reference genes are to be used and we determined that the most suitable seem to be PPIA and GAPD. PMID- 26898427 TI - Sulforaphane suppresses in vitro and in vivo lung tumorigenesis through downregulation of HDAC activity. AB - BACKGROUND: Sulforaphane (SFN), an isothiocyanate isolated from broccoli, has been reported to have chemopreventive activity. However, the effects of SFN on lung cancer have not been investigated. In this study, we investigate the chemopreventive role of SFN through the inhibition of histone deacetylase (HDAC) in two different lung cancer cells by in vitro and in vivo mouse models. METHODS: A549 and H1299 lung cancer cells were treated with SFN for 48h. The HDAC activity, expression of acetylated histones H3 and H4, apoptosis and cell cycles were analyzed by western blot, qRT-PCR and flow cytometry. A549 cells were implanted into the immunocompromised mice for xenografts. RESULTS: The results showed that SFN inhibited HDAC activity and increased the levels of acetylated histones H3 and H4 in all two lung cancer cells. Further, SFN induced apoptosis, increased the accumulation of cells at G0/G1 and G2/M and arrest cells at S phase. We also found that a concomitant increase of apoptosis related proteins by SFN administration. More interestingly, SFN suppressed the lung cancer growth in xenograft mouse model. CONCLUSION: In conclusion, the chemopreventive effect of SFN is associated with inhibition of HDAC activity, thereby attenuating lung cancer growth. Therefore, these findings suggest that SFN may be a therapeutic agent for lung cancer through the inhibition of HDAC. PMID- 26898428 TI - CpG oligodeoxynucleotide-loaded PAMAM dendrimer-coated magnetic nanoparticles promote apoptosis in breast cancer cells. AB - One major application of nanotechnology in cancer treatment involves designing nanoparticles to deliver drugs, oligonucleotides, and genes to cancer cells. Nanoparticles should be engineered so that they could target and destroy tumor cells with minimal damage to healthy tissues. This research aims to develop an appropriate and efficient nanocarrier, having the ability of interacting with and delivering CpG-oligodeoxynucleotides (CpG-ODNs) to tumor cells. CpG-ODNs activate Toll-like receptor 9 (TLR9), which can generate a signal cascade for cell death. In our study, we utilized three-layer magnetic nanoparticles composed of a Fe3O4 magnetic core, an aminosilane (APTS) interlayer and a cationic poly(amidoamine) (PAMAM) dendrimer. This will be a novel targeted delivery system to enhance the accumulation of CpG-ODN molecules in tumor cells. The validation of CpG-ODN binding to DcMNPs was performed using agarose gel electrophoresis, UV spectrophotometer, XPS analyses. Cytotoxicity of conjugates was assessed in MDA MB231 and SKBR3 cancer cells based on cell viability by XTT assay and flow cytometric analysis. Our results indicated that the synthesized DcMNPs having high positive charges on their surface could attach to CpG-ODN molecules via electrostatic means. These nanoparticles with the average sizes of 40+/-10nm bind to CpG-ODN molecules efficiently and induce cell death in MDA-MB231 and SKBR3 tumor cells and could be considered a suitable targeted delivery system for CpG ODN in biomedical applications. The magnetic core of these nanoparticles represents a promising option for selective drug targeting as they can be concentrated and held in position by means of an external magnetic field. PMID- 26898429 TI - Single nucleotide polymorphisms in DNA repair genes and the risk of laryngeal cancer: A meta-analysis. AB - Laryngeal cancer is the most common type of head and neck cancer with poor prognosis and high relapse rate. Several genes involved in DNA repair pathways have been identified for their potential role in laryngeal cancer risk. However, the results remain inconclusive. The aim of this study was to investigate the association between polymorphisms of XRCC1 Arg399Gln, XRCC3 Thr241Met, and XPD Lys751Gln and laryngeal cancer risk. Relevant case-control studies published between 2000 and 2015 were retrieved. The odds ratio (OR) with its 95% confidence interval (CI) were employed to calculate the strength of correction. Finally, total 16 articles (8 for XRCC1 Arg399Gln variant, 8 for XRCC3 Thr241Met variant and 7 for XPD Lys751Gln variant) were screened out, including 2242 laryngeal cancer cases and 3811 matched controls. Overall, our results found that only AA genotype of the XRCC1 gene Arg399Gln polymorphism under the homozygous model was associated with increased the risk of patients with laryngeal cancer (AA vs. GG: OR=1.29, 95% CI=1.00-1.65, P=0.05). This significant relationship was not detected between XRCC3 Thr241Met, XPD Lys751Gln polymorphisms and laryngeal cancer risk (P>0.05). In conclusions, our results suggested that XRCC1 gene Arg399Gln polymorphism might be a risk factor for laryngeal cancer. Future studies with large-scales, more ethnicities are still needed to further evaluate the role of these three genes mutations in laryngeal cancer susceptibility. PMID- 26898430 TI - Pioglitazone up-regulates long non-coding RNA MEG3 to protect endothelial progenitor cells via increasing HDAC7 expression in metabolic syndrome. AB - Long non-coding RNA (lncRNA) maternally expressed 3 (MEG3) is expressed in endothelial cells and involved in angiogenesis and vascular function. It was proposed that MEG3 participates in the process of endothelial progenitor cells (EPCs) functions in metabolic syndrome (MetS). In this study, the circulating EPCs number and function were decreased in MetS subjects. The MEG3 expression was expressed at a lower level and microRNA-140-5p (miR-140-5p) was expressed at a higher level in circulating EPCs of subjects with MetS. Pioglitazone reversed the alterations of EPCs function and the expression levels of MEG3 and miR-140-5p in EPCs. In bone marrow-derived EPCs exposed to palmitate, down-regulation of miR 140-5p canceled the increase of MEG3 expression level induced by Pioglitazone. Overexpression of MEG3 resulted in the down-regulation of miR-140-5p. The luciferase reporter assay and RIP assay showed that MEG3 targeted miR-140-5p. In addition, the HDAC7 expression levels were regulated by miR-140-5p and MEG3. These findings demonstrated that Pioglitazone up-regulated MEG3 expression to protect EPCs via decreasing miR-140-5p expression and increasing HDAC7 expression in MetS, which may be a novel therapeutic target for preventing and treating MetS. PMID- 26898431 TI - Overexpressing NKx2.5 increases the differentiation of human umbilical cord drived mesenchymal stem cells into cardiomyocyte-like cells. AB - BACKGROUND: Nkx2.5 is one of the transcription factors in early myocardial cell development and Nkx2.5 gene expression increased gradually in the course of stem cells differentiation. In this study, this study aimed to investigate whether overexpression of NKx2.5 increases human umbilical cord drived mesenchymal stem cells (hUCMSCs) transdifferentiation into a cardiac phenotype in vitro. METHODS: hUCMSCs were transduced with Nkx2.5 at the third passage (transduced group). Gene expression of cTnI, Desmin, Nkx2.5 and GATA-4 in transduced group was analyzed using real-time PCR and immunohistochemistry, and compared with no-transduced hUCMSCs (control group), which were transfected with green fluorescent protein (GFP) only. RESULTS: Compared with control group, hUCMSCs in transduced group were shown by immunofluorescence to have higher expression of Nkx2.5. After incubation for 4 weeks, the mRNA and protein expression of cardiac genes, including cTnI, Desmin, Nkx2.5 and GATA-4, were up- regulated in transduced group compared with control group (P<0.05). CONCLUSIONS: Overexpression of Nkx2.5 significantly promotes the differentiation of hUCMSCs into cardiomyocytes and increases the expression of cTnI, Desmin, Nkx2.5, and GATA-4. PMID- 26898432 TI - Protein regulator of cytokinesis 1 overexpression predicts biochemical recurrence in men with prostate cancer. AB - BACKGROUND: Protein regulator of cytokinesis 1 (PRC1) has been reported to be implicated into the completion of cytokinesis and is dys-regulated in a cancer specific manner. However, it roles in human prostate cancer (PCa) remain unclear. In the current study, we aimed to investigate the expression pattern of PRC1 and its clinical significance in this malignancy. MATERIALS AND METHODS: PRC1 protein expression in human PCa and non-cancerous prostate tissues was detected by immunohistochemistry, which was validated by microarray-based Taylor data at mRNA level. Then, the associations of PRC1 expression with clinicopathological features and clinical outcome of PCa patients were statistically analyzed. RESULTS: PRC1 expression in PCa tissues, at both mRNA and protein levels, were significantly higher than those in non-cancerous prostate tissues. In addition, the PCa patients with PRC1 overexpression more frequently had high Gleason score, advanced pathological stage, positive metastasis, short overall survival time and positive PSA failure than those with low Gleason score, early pathological stage, negative metastasis, long overall survival time and negative PSA failure (all P<0.05). Moreover, PRC1 expression was identified as an unfavorable prognostic factor of biochemical recurrence-free survival in PCa patients (P<0.001). CONCLUSION: These findings suggest that the aberrant expression of PRC1 may predict biochemical recurrence in men with PCa highlighting its potential as a prognostic marker of this malignancy. PMID- 26898433 TI - The emerging role of GPR50 receptor in brain. AB - GPR50 receptor one of the member of G protein-coupled receptors (GPCRs) is extensively expressed in the pituitary, hypothalamus,cortex, midbrain, pons, amygdala, and in several brainstem nuclei. The exact function of this receptor in brain is remains unclear. This review presents current knowledge regarding the function of GPR50 receptor in brain, with a focus on role of this receptor in the hypothalamus-pituitary-adrenal (HPA) axis and the glucocorticoid receptor (GR) signaling, leptin signaling, adaptive thermogenesis, torpor, neurite outgrowth, and self-renewal and neuronal differentiation of neural progenitor cells NPCs. Although the results are encouraging, further research is needed to clarify GPR50 role in neurobiology of mood disorders, adaptive thermogenesis, torpor, and in the pathophysiology of neurological disorders. PMID- 26898434 TI - The role of oncomirs in the pathogenesis and treatment of breast cancer. AB - Breast cancer, the most common cancer among women, is a heterogeneous and complex disease, which detail of its precise progression mechanisms is less understood. So, an improved comprehension of the precise molecular mechanisms leading to disease progression and design of effective targeted therapies are required for patients with breast cancer. MicroRNAs demonstrate an uncovered class of small and endogenous non-coding RNAs and play an important role in the normal biological processes, including cell differentiation, proliferation and apoptosis. Some miRNAs, known as oncomiR, show different expression levels in cancer and are capable to effect on cellular transformation, carcinogenesis and metastasis and are characterized by high expression levels in tumors compared to normal tissues. Therefore, oncomiRs can be considered as prognostic biomarkers and therapeutic targets in different types of cancers. Moreover, the utilization of oncomiRs as therapeutic targets for cancer is promising. Accordingly, there is evidence which implies an important role of various oncogenic microRNAs in immunopathogenesis of breast cancer. In this review we will discuss about the role of various oncomiRs such as miR-21, miR-155, miR-10b, and miR-221/222 in the pathogenesis and treatment of breast cancer. PMID- 26898435 TI - Vascular endothelial growth factor receptor-1 (VEGFR-1) signaling enhances angiogenesis in a surgical sponge model. AB - BACKGROUND: Vascular endothelial growth factor (VEGF)-A binds to both VEGF receptor (VEGFR)-1 and VEGFR-2, thereby promoting angiogenesis. It is widely accepted that VEGF-A, especially VEGFR-2, is a central player in angiogenesis, however the role of VEGFR-1 in angiogenesis remains unclear. The present study was conducted to examine the role of VEGFR-1 signaling in angiogenesis, using a quantitative in vivo angiogenesis model. METHODS: Polyurethane sponge disks were implanted into dorsal subcutaneous tissue of mice. Angiogenesis was estimated by determining the number of CD31(+) vessels by immunohistochemical analysis. The expression of pro-angiogenic factors was quantified by reverse transcription quantitative polymerase chain reaction. RESULTS: Compared to control IgG-treated mice, the number of CD31(+) vessels in the sponge implant was significantly suppressed in anti-VEGF-A neutralizing antibody-treated mice. CD31(+) vessel counts were suppressed in VEGFR-1 tyrosine kinase knockout (TKKO) mice, at the same level as in VEGFR-2 tyrosine kinase inhibitor (ZD6474)-treated mice compared to wild-type (WT) mice. The accumulation of VEGFR-1(+) cells in granulation tissue was significantly suppressed in VEGFR-1 TKKO mice compared to WT mice. In addition, expression of the pro-angiogenic growth factors, VEGF-A, matrix metalloproteinase-2, interleukin-6, and basic fibroblast growth factor in granulation tissue was suppressed in VEGFR-1 TKKO mice. A bone marrow (BM) transplantation experiment showed that the number of VEGFR-1(+) BM-derived cells and angiogenesis were significantly suppressed in VEGFR-1 TKKO mice transplanted with green fluorescent protein (GFP)(+) VEGFR-1 TKKO BM compared to WT mice transplanted with GFP(+) WT BM. CONCLUSIONS: These results suggest that the VEGFR 1 tyrosine kinase signaling has an effect on angiogenesis. A selective VEGFR-1 agonist/antagonist could be a candidate therapeutic agent to control angiogenesis with recruitment of BM cells. PMID- 26898436 TI - Protective effect of vitamin E against ethanol-induced small intestine damage in rats. AB - The role of oxidative stress and inflammatory reaction has been reported in various ethanol-induced complications. The purpose of this study was to evaluate the effect of ethanol-induced structural alteration, oxidative stress, and inflammatory reaction on the small intestine of rats, and plausible protective effect of vitamin E to determine whether it inhibits the abnormality induced by ethanol in the small intestine. Twenty-four male wistar rats were divided into three groups, namely: Control, ethanol, and vitamin E treated ethanol groups. After six weeks of treatment, the small intestine length, villus height, crypt depth and muscular layer thickness, oxidative stress, and inflammatory parameters showed significant changes in the ethanol treated group compared to the control group. Vitamin E consumption along with ethanol ameliorated structural alteration of the small intestine and reduced the elevated amount of oxidative stress and inflammatory markers such as protein carbonyl, OX-LDL, IL-6, Hcy, and TNF-alpha. Furthermore, their total antioxidant capacity was increased significantly compared to that of the ethanol group. These findings indicate that ethanol induces the small intestine abnormality by oxidative and inflammatory stress, and that these effects can be alleviated by using vitamin E as an antioxidant and anti-inflammatory molecule. PMID- 26898437 TI - Co-combination of islets with bone marrow mesenchymal stem cells promotes angiogenesis. AB - BACKGROUND: Islet transplantation is a commonly therapeutic strategy for diabetes mellitus. However, avascular phase and the poor formation of blood vessels in the late period lead to islet allograft loss which contributed to inefficiency and short-acting of islet transplantation. Recently, to speed up new angiogenesis and increase the density of blood vessels around transplanted islets became the hotspot in research of islet transplantation. METHODS: In this study, we undergone co-combination transplantation of allogeneic islet and bone marrow mesenchymal stem cells (BM-MSCs) into non-obese diabetic (NOD) mice and investigated the influence of BM-MSCs in transplanted islet function and neovascularization. RESULTS: In mice of co-combination transplantation of islet with BM-MSCs, level of blood glucose was improved compared with only BM-MSCs transplanted mice; proliferation of islet cell was enhanced while apoptosis of islet cell was reduced; 2, 4, and 8 weeks post transplantation, peripheral vascular density of islet grafts were significantly more than the islet transplantation group alone; donor lymphocytic chimerism in graft was increased. In result of immunofluorescence analysis, we observed that BM-MSCs can migrate to transplanted islet, differentiate into vascular smooth muscle cells (VSMC) and vascular endothelial cells (VEC), and also secrete vascular endothelial growth factor (VEGF). CONCLUSION: BM-MSCs can migrate to transplanted islet and promote neovascularization. Also, it enhanced allograft immune tolerance of islet grafts via increasing donor lymphocytic chimerism. PMID- 26898438 TI - Molecular regulation of galectin-3 expression and therapeutic implication in cancer progression. AB - Galectin-3, a multifunctional protein, distributes inside and outside cells and plays an important role in tumor cell adhesion, proliferation, differentiation, angiogenesis, and metastasis in multiple tumors. Changes in galectin-3 expression are commonly seen in cancer and pre-cancerous conditions. Therefore, to understand the molecular regulation of galectin-3 expression could aid the development of new approach for cancer treatment. This review summarizes different expression of galectin-3 in cancer cells and patients' serum, the regulation mechanism and the potential therapeutic targets of galectin-3 in cancer progression. PMID- 26898439 TI - Increased expression of LncRNA PANDAR predicts a poor prognosis in gastric cancer. AB - Long non-coding RNAs (lncRNAs) are emerging as biomarkers and as important regulators in biological processes and tumorigenesis in cancer. PANDAR (promoter of CDKN1A antisense DNA damage activated RNA) serves as biomarkers and involves in development of multiple cancers. However, its clinical value of PANDAR in gastric cancer is still unknown. Hence, we carried out the present study aiming to identify the clinical significance of PANDAR in gastric cancer patients. We analyzed the expression levels of PANDAR in 100 paired gastric cancer tissues using Quantitative Real-time PCR. Our results showed that the expression of PANDAR was significantly increased in gastric cancer tissues compared with paired adjacent normal tissues. Furthermore, high expression of PANDAR was correlated with depth of invasion, TNM stage and lymphatic metastasis. Importantly, high expression of PANDAR could serve as an independent unfavorable prognostic role in gastric cancer. In conclusion, PANDAR may be a potential novel biomarker that predicts prognosis in gastric cancer. PMID- 26898440 TI - MicroRNA-132 cause apoptosis of glioma cells through blockade of the SREBP-1c metabolic pathway related to SIRT1. AB - BACKGROUND: The inhibition role of miRNA (microRNA or miR) on cancer signaling pathways has been used to prospective cancer treatment. SIRT1 might promote tumorigenesis in human glioma. METHODS: Here, we investigated whether miR-132 regulate the expression of SIRT1 and its downstream SREBP (Sterol regulatory element-binding protein)-lipogenesis-cholesterogenesis metabolic pathway in human glioma cells. Furthermore, we studied the effect on biology function of glioma cell induced by miR-132. RESULTS: MiR-132 inhibited SIRT1 and SREBP-1c expression and downregulated their targeted genes, including HMGCR and FASN. MiR-132 suppressed the cell growth, tumorigenicity, the invasion of glioma cells and migration as well as promoted their apoptosis. The pathways associated with cancer progression and tumorigenicity, and induce glioma cell apoptosis has been inhibited by miR-132 involving in a caspase-dependent apoptotic mechanism. CONCLUSIONS: The recovery of miR-132 resulted in caspase-dependent apoptotic death in glioma cells. MiR-132 that was newly discovered represents a newly targeting mechanism in treatment for glioma. PMID- 26898441 TI - Short-term ursolic acid promotes skeletal muscle rejuvenation through enhancing of SIRT1 expression and satellite cells proliferation. AB - Ursolic acid (UA) is a triterpenoid compound, which exerts its influences on the skeletal muscles. However, the mechanisms underlying these effects are still unclear. In this study, muscle satellite cells were isolated and purified by high throughput pre-plating method (~>60%) from 10 days old mice skeletal muscles. Evaluation of paired-box 7 (Pax7) expressions then confirmed the purification. Treatment of the cells with UA showed that UA up-regulated SIRT1 (~35 folds) and overexpressed PGC-1alpha (~175 folds) gene significantly. Moreover, the number of muscle satellite cells, which accompanied by initiation of neomyogenesis in the animal skeletal muscles, was increased (~3.4 times). We also evaluated UA mediated changes in the cellular energy status in the skeletal muscles. The results revealed that in the UA-treated mice, ATP and ADP contents in the various skeletal muscle tissue types, including: Gastrocnemius (Gas), Tibialis Anterior (Tib) and Gluteus Maximus (Glu) have been significantly decreased (P<=0.001); 2.2, 3.2, 2 times for ATP, and 9.6, 35.7, 11.6 times for ADP, respectively; however to compensate this process mitochondrial biogenesis occurred (12.33%+/ 1.5 times). Furthermore, a rise in ATP/ADP ratio was observed 2.5, 4.5, 2.05 times for Gas, Tib and Glu muscles, respectively (P<=0.001). Alternatively, UA enhanced the expression of myoglobin (~2 folds) in concert with remodeling of glycolytic muscle fibers to mainly fast IIA (~30%) and slow-twitch (~4%) types as well. Finally, our study indicated that UA indirectly mimicked beneficial effects of short-term calorie restriction and exercise (fast-oxidative) by directing the skeletal muscle composition toward oxidative metabolism. PMID- 26898442 TI - Paeoniflorin inhibits proliferation and invasion of breast cancer cells through suppressing Notch-1 signaling pathway. AB - Paeoniflorin (PF), one of the major active ingredients of Chinese peony, was reported to possess anti-tumor effect. However, the role of PF in breast cancer remains to be clarified. Therefore, in this context, the present study investigated the effects of PF on breast cancer cell proliferation and invasion, as well as the underlying mechanism. Our results found that PF suppressed the proliferation and invasion of breast cancer cells. We further demonstrated that PF down-regulated the expression of Notch-1; in addition, overexpression of Notch 1 reversed PF-inhibited proliferation and invasion, and knockdown of Notch-1 enhanced PF-inhibited proliferation and invasion in breast cancer cells. In conclusion, the present study suggests that PF inhibits proliferation and invasion of breast cancer cells through suppressing Notch-1 signaling pathway. Therefore, PF may represent a chemopreventive and/or therapeutic agent in the prevention of breast cancer. PMID- 26898443 TI - Ligustrazine disrupts lipopolysaccharide-activated NLRP3 inflammasome pathway associated with inhibition of Toll-like receptor 4 in hepatocytes. AB - Intestine microbial products may translocate into the liver via portal vein and trigger or exacerbate hepatocyte inflammatory responses during liver injury. The NLRP3 inflammasome pathway plays a key role in regulation of inflammatory cytokines in response to bacterial products. The present study was aimed to investigate the effects of ligustrazine, a natural alkaloid compound, on the NLRP3 inflammasome pathway activation and interleukin-1beta (IL-1beta) generation in hepatocytes. We cultured human LO2 hepatocytes and treated them with lipopolysaccharide (LPS), a membrane component of Gram-negative bacteria, for mimicking hepatic exposure to microbial products in vitro. The results demonstrated that LPS upregulated NLRP3 and cleaved-caspase-1, and promoted the expression and secretion of IL-1beta in LO2 cells. Ligustrazine was found to reduce NLRP3 and cleaved-caspase-1, prevented IL-1beta cleavage, and decreased IL 1beta secretion into extracellular environment. Further examinations showed that LPS upregulated the expression of Toll-like receptor 4 (TLR4), but ligustrazine repressed TLR4 expression in LPS-treated hepatocytes. Moreover, pharmacological inhibition of TLR4 by its specific inhibitor TAK-242 downregulated NLRP3 and cleaved-caspase-1, and combination treatment with TAK-242 and ligustrazine led to more significant inhibitory effects on the NLRP3 pathway. TAK-242 also reduced cleaved-IL-1beta, and this reducing effect was enhanced by ligustrazine. Collectively, the current results revealed that ligustrazine interrupted LPS activated NLRP3 inflammasome signaling and reduced generation of IL-1beta in hepatocytes, which was associated with inhibition of TLR4. This study uncovered a novel mechanism for ligustrazine as a potential hepatoprotective agent. PMID- 26898444 TI - Comparative effects of catechin, epicatechin and N-Omega-nitroarginine on quinolinic acid-induced oxidative stress in rat striatum slices. AB - The aim of this work was to compare the effects of catechin (CAT), epicatechin (EPI) and N-omega-l-nitroarginine (L-NARG) on different endpoints of oxidative stress induced by quinolinic acid (QUIN) in a simple tissue preparation, rat striatal slices - with particular emphasis in the glutathione system - in order to provide revealing information on the antioxidant efficacy of these agents in an excitotoxic model. METHODS: Rat striatal slices were incubated for 1h in the presence of 100 MUM QUIN and/or 85 MUM CAT or EPI, or 100 MUM L-NARG. Lipid peroxidation (LP) and the levels of reduced and oxidized glutathione (GSH and GSSG) were determined. RESULTS: The three agents tested completely blocked the QUIN-induced lipid peroxidation and recovered the QUIN-induced altered GSH/GSSG balance. No statistical differences were detected among the protective effects exerted by these antioxidants, suggesting similar efficacy and common antioxidant mechanisms. The antioxidant properties exhibited by these molecules on the excitotoxic model tested herein support an active role of glutathione and prompt their use as therapeutic tools in models of neurodegenerative disorders. PMID- 26898445 TI - RO-3306 prevents postovulatory aging-mediated spontaneous exit from M-II arrest in rat eggs cultured in vitro. AB - BACKGROUND: Postovulatory aging-mediated spontaneous exit from metaphase-II (M II) arrest deteriorates egg quality and limits assisted reproductive technologies outcome (ART) outcome. Present study was aimed to find out whether RO-3306, specific cyclin dependent kinase 1 (Cdk1) inhibitor could protect against postovulatory aging-mediated spontaneous exit from M-II arrest in rat eggs cultured in vitro. METHODS: Freshly ovulated M-II arrested eggs were exposed to various concentrations of RO-3306 for 3h in vitro. The morphological changes, percentage of spontaneous exit from M-II arrest, total and specific phosphorylation status of Cdk1, cyclin B1 level and Cdk1 activity were analyzed. RESULTS: Data suggest that RO-3306 protected postovulatory aging-mediated spontaneous exit from M-II arrest in a concentration-dependent manner. Postovulatory aging increased Thr14/Tyr15 phosphorylated Cdk1 level, decreased Thr161 phosphorylated Cdk1 as well as cyclin B1 levels and increased Cdk1 activity in aged eggs cultured in vitro. On the other hand, RO-3306 protected postovulatory aging-induced changes in specific phosphorylation of Cdk1, cyclin B1 level, inhibited the kinase activity and prevented spontaneous exit from M-II arrest. CONCLUSIONS: Our results suggest that postovulatory aging destabilizes MPF by modulating specific phosphorylation of Cdk1 and cyclin B1 level. RO-3306 prevented these changes and maintained M-II arrest in rat eggs cultured in vitro. Hence, maintenance of M-II arrest in ovulated eggs using RO-3306 could be beneficial to increase the number of eggs available for various ART programs. PMID- 26898447 TI - Estrogen repression of microRNA as a potential cause of cancer. AB - MicroRNAs (miRNAs) are endogenous small molecules that regulate gene expression and have been implicated in the pathogenesis of many human diseases, including cancer. This review describes the results that show a global repression in miRNA expression in various tumors and cancer cell lines. Intriguingly, recent discoveries have shown a widespread downregulation of miRNA after exposure to the steroid hormone estrogen. The integration of the results suggests that estrogen dependent repression of miRNA is a potential cause of cancer. PMID- 26898446 TI - Treatment of bleomycin-induced pulmonary fibrosis by inhaled tacrolimus-loaded chitosan-coated poly(lactic-co-glycolic acid) nanoparticles. AB - Pulmonary fibrosis is a chronic lung disease characterized by inflammation and collagen deposition, with an estimated mortality rate exceeding 70%. Here, we evaluated the therapeutic effectiveness of inhaled tacrolimus-loaded chitosan coated poly(lactic-co-glycolic acid) nanoparticles (chitosan TAC PLGA-NPs) in a bleomycin-induced pulmonary fibrosis mouse model. Chitosan TAC PLGA-NPs were fabricated using an o/w emulsification diffusion method, and uncoated TAC PLGA NPs and chitosan TAC PLGA-NPs were spherical with approximate diameters of 320 and 441 nm, respectively. The zeta potential of chitosan TAC PLGA-NPs (+13.6 mV) was increased significantly by chitosan-coating versus uncoated TAC PLGA-NPs ( 28.3 mV). The incorporation efficiency of tacrolimus was 37.7%, and the tacrolimus was gradually released until about 5 day. Direct inhalation of chitosan TAC PLGA-NPs (TAC 180 MUg/mouse) twice a week produced marked anti fibrotic efficacy in mice with bleomycin-induced pulmonary fibrosis, which was much better than the efficacy resulting from daily oral administration (TAC 300 MUg/mouse) on the basis of hematoxylin/eosin and Masson's trichrome staining assessments. Imaging of lung deposition showed that chitosan TAC PLGA-NPs were located well in the lungs and gradually faded over 96 h. The pulmonary delivery of tacrolimus could be therapeutically efficacious for treating pulmonary fibrosis. TAC-loaded PLGA nanoparticles should be considered to be an efficient sustained-release type inhalation system that reduces administration frequency and relevant side effects. PMID- 26898448 TI - Chemopreventive action of non-steroidal anti-inflammatory drugs on the inflammatory pathways in colon cancer. AB - Non-steroidal anti-inflammatory drugs (NSAIDs) are emerging as novel chemopreventive agents against a variety of cancers owing to their capability in blocking the tumor development by cellular proliferation and by promoting apoptosis. Inflammation is principal cause of colon carcinogenesis. A missing link between inflammation and cancer could be the activation of NF-kappaB, which is a hallmark of inflammatory response, and is commonly detected in malignant tumors. Therefore, targeting pro-inflammatory cyclooxygenase enzymes and transcription factors will be profitable as a mechanism to inhibit tumor growth. In the present study, we have studied the role of various pro-inflammatory enzymes and transcription factors in the development of the 1,2-dimethylhydrazine dihydrochloride (DMH)-induced colorectal cancer and also observed the role of three NSAIDs, viz., Celecoxib, Etoricoxib and Diclofenac. Carcinogenic changes were observed in morphological and histopathological studies, whereas protein regulations of various biomolecules were identified by immunofluorescence analysis. Apoptotic studies was done by TUNEL assay and Hoechst/PI co-staining of the isolated colonocytes. It was found that DMH-treated animals were having an over-expression of pro-inflammatory enzymes, aberrant nuclear localization of activated cell survival transcription factor, NF-kappaB and suppression of anti inflammatory transcription factor PPAR-gamma, thereby suggesting a marked role of inflammation in the tumor progression. However, co-administration of NSAIDs has significantly reduced the inflammatory potential of the growing neoplasm. PMID- 26898449 TI - Isolation, identification and molecular docking as cyclooxygenase (COX) inhibitors of the main constituents of Matricaria chamomilla L. extract and its synergistic interaction with diclofenac on nociception and gastric damage in rats. AB - Chamomile (Matricaria chamomilla L., Asteraceae) is a medicinal plant widely used as remedy for pain and gastric disorders. The association of non-steroidal anti inflammatory drugs (NSAIDs) with medicinal plant extracts may increase its antinociceptive activity, permit the use of lower doses and limit side effects. The aim was to isolate and identify the main chemical constituents of Matricaria chamomilla ethanolic extract (MCE) as well as to explore their activity as cyclooxygenase (COX) inhibitors in silico; besides, to examine the interaction between MCE and diclofenac on nociception in the formalin test by isobolographic analysis, and to determine the level of gastric injury in rats. Three terpenoids, alpha-bisabolol, bisabolol oxide A, and guaiazulene, were isolated and identified by (1)H NMR. Docking simulation predicted COX inhibitory activity for those terpenoids. Diclofenac, MCE, or their combinations produced an antinociceptive effect. The sole administration of diclofenac and the highest combined dose diclofenac-MCE produced significant a gastric damage, but that effect was not seen with MCE alone. An isobologram was constructed and the derived theoretical ED35 for the antinociceptive effect was significantly different from the experimental ED35; hence, the interaction between diclofenac and MCE that mediates the antinociceptive effect is synergist. The MCE contains three major terpenoids with plausible COX inhibitory activity in silico, but alpha-bisabolol showed the highest affinity. Data suggest that the diclofenac-MCE combination can interact at the systemic level in a synergic manner and may have therapeutic advantages for the clinical treatment of inflammatory pain. PMID- 26898450 TI - Carvedilol protects bone marrow stem cells against hydrogen peroxide-induced cell death via PI3K-AKT pathway. AB - Carvedilol, a nonselective beta-adrenergic receptor blocker, has been reported to exert potent anti-oxidative activities. In the present study, we aimed to investigate the effects of carvedilol against hydrogen peroxide (H2O2)-induced bone marrow-derived mesenchymal stem cells (BMSCs) death, which imitate the microenvironment surrounding transplanted cells in the injured spinal cord in vitro. Carvedilol significantly reduced H2O2-induced reactive oxygen species production, apoptosis and subsequent cell death. LY294002, the PI3K inhibitor, blocked the protective effects and up-regulation of Akt phosphorylation of carvedilol. Together, our results showed that carvedilol protects H2O2-induced BMSCs cell death partly through PI3K-Akt pathway, suggesting carvedilol could be used in combination with BMSCs for the treatment of spinal cord injury by improving the cell survival and oxidative stress microenvironments. PMID- 26898451 TI - USO1 promotes tumor progression via activating Erk pathway in multiple myeloma cells. AB - OBJECTIVE: This study aimed to explore the influence of USO1 on multiple myeloma (MM) cell proliferation and apoptosis and the related molecular mechanism. METHODS: The expression of USO1 and MIF in MM tissues and cells, normal bone marrow tissues and cells were determined by qRT-PCR and western blot assay. The cell proliferation and apoptosis of MM cells before and after knockdown of USO1 were determined by MTT assay and flow cytometry, respectively. Before and after knockdown of USO1, the expression of the proliferation-related genes cyclin D1, Mcm2 and PCNA in MM cells was determined by qRT-PCR and western blot assay. The protein level of p-Erk1/2 and MIF was determined by western blot assay and ELISA, respectively. RESULTS: The expression levels of USO1 and MIF in MM tissues and cells were much higher than those in normal bone marrow tissues and cells. Knockdown of USO1 resulted in the inhibited ability of cell proliferation and induced cell apoptosis. The expression of cyclin D1, Mcm2, PCNA and p-Erk1/2 decreased significantly after knockdown of USO1 as well as the decreased MIF secretion. CONCLUSION: USO1 gene may be a promising target for the therapy of human MM and its diagnosis marker. PMID- 26898452 TI - Drug discovery of neurodegenerative disease through network pharmacology approach in herbs. AB - Neurodegenerative diseases, referring to as the progressive loss of structure and function of neurons, constitute one of the major challenges of modern medicine. Traditional Chinese herbs have been used as a major preventive and therapeutic strategy against disease for thousands years. The numerous species of medicinal herbs and Traditional Chinese Medicine (TCM) compound formulas in nervous system disease therapy make it a large chemical resource library for drug discovery. In this work, we collected 7362 kinds of herbs and 58,147 Traditional Chinese medicinal compounds (Tcmcs). The predicted active compounds in herbs have good oral bioavailability and central nervous system (CNS) permeability. The molecular docking and network analysis were employed to analyze the effects of herbs on neurodegenerative diseases. In order to evaluate the predicted efficacy of herbs, automated text mining was utilized to exhaustively search in PubMed by some related keywords. After that, receiver operator characteristic (ROC) curves was used to estimate the accuracy of predictions. Our study suggested that most herbs were distributed in family of Asteraceae, Fabaceae, Lamiaceae and Apocynaceae. The predictive model yielded good sensitivity and specificity with the AUC values above 0.800. At last, 504 kinds of herbs were obtained by using the optimal cutoff values in ROC curves. These 504 herbs would be the most potential herb resources for neurodegenerative diseases treatment. This study would give us an opportunity to use these herbs as a chemical resource library for drug discovery of anti-neurodegenerative disease. PMID- 26898453 TI - Transforming growth-beta 1 contributes to isoflurane postconditioning against cerebral ischemia-reperfusion injury by regulating the c-Jun N-terminal kinase signaling pathway. AB - AIM: Cerebral ischemia-reperfusion (I/R) injury is a devastating complication in the perioperative period. Transforming growth factor beta (TGF-beta) is a key protein that can participate in the repair and control process responses after I/R injury. Isoflurane is widely used in neurosurgery. Previous studies have shown that isoflurane preconditioning plays an important role in neuroprotection. However, the effects of isoflurane postconditioning on cerebral I/R injury have not yet been elucidated. In the present study, we evaluated the protective effect of isoflurane postconditioning against cerebral I/R injury and investigated the role of the TGF-beta signaling pathway and the downstream c-Jun N-terminal kinase (JNK) signaling pathway in neuroprotective mechanism. In particular, the JNK signaling pathway emerges as a possible target for brain repair after stroke. METHODS: Cerebral I/R injury was produced in SD rat by using the middle cerebral artery occlusion model for 90 min, followed by 24h reperfusion. Postconditioning by inhalation of isoflurane was performed at different concentrations (1.5%, 3.0%, and 4.5%) for 1h after ischemia at the starting time point of reperfusion. The protective effect was tested by neurological deficit scoring with 2,3,5 triphenyl tetrazolium chloride and propidium iodide (PI) staining. Apoptosis of CA1 cells in the hippocampus was detected by TUNEL method. Expression levels of TGF-beta1, Smad 2/3, p-Smad2/3, JNK, and p-JNK were determined by immunostaining and Western blot. RESULTS: Postconditioning by isoflurane at 1.5% and 3.0% concentrations significantly decreased the neurobehavioral deficit scores and infarct volume compared with the I/R group, but no significant difference in neurobehavioral deficit score was detected between the I/R and 4.5% isoflurane postconditioning groups. Additionally, 1.5% isoflurane postconditioning decreased the numbers of PI-positive cells at 24h after reperfusion compared with the I/R group. TGF-beta1 and p-Smad2/3 protein gradually increased after I/R injury, with the highest values observed in the 1.5% and 3% isoflurane postconditioning groups. For Smad2/3 protein expression, no differences existed among all groups. After inducing the TGF-beta/SMAD3 signaling pathway specific blocker (LY2157299), the neurological deficit scores increased, infarct volumes enlarged, apoptosis increased, and PI-positive CA1 cells in the hippocampus also increased. The expression levels of TGF-beta1 and p-Smad2/3 proteins were downregulated. During the pre-injection of LY2157299, the expression levels of TGF-beta1 and p-Smad2/3 decreased significantly, but compared with the sham group, the expression level of p-JNK significantly increased. When the injection of LY2157299 was abolished, the expression of p-JNK significantly decreased. The expression levels of p-JNK and TGF-beta1 significantly decreased when LY2157299 and SP600125 were injected simultaneously. However, the protective effect mediated by SP600125 completely disappeared, and the role of LY2157299 became dominant. Compared with the sham group, the expression of TGF-beta1 was almost unchanged by the injection of SP600125 alone, but the expression of p-JNK significantly decreased. CONCLUSIONS: Up to 1.5% isoflurane can upregulate the expression of TGF-beta1 and downregulate that of p-JNK, which significantly mitigated I/R injury, leading to cerebral injury. However, this protective effect was abrogated when the TGF-beta1 signaling pathway was blocked by LY2157299. Overall, the present results provided valid evidence to demonstrate that TGF-beta1 contributes to isoflurane postconditioning against cerebral I/R injury by inhibiting the JNK signaling pathway. PMID- 26898454 TI - In vitro and in vivo efficacy and safety evaluation of metapristone and mifepristone as cancer metastatic chemopreventive agents. AB - Malignant melanoma, the most deadly form of skin cancer, has a high propensity for metastatic spread and is notoriously chemotherapy-resistant. Metapristone is the primary metabolite of mifepristone (RU486) and shows biological activities similar to RU486. In the present study, we comprehensively investigated the efficacy of metapristone as a metastatic chemopreventive against melanoma B16F10 cells in vitro and in vivo, and evaluated the safety profile of both drugs in mice. Metapristone showed less cytostatic effect in vitro and in vivo in comparison with mifepristone. However, metapristone interfered the adhesion of B16F10 cells to fibronectin by down-regulating cellular expression of integrin alpha4. Chemopreventive pretreatment followed by oral administration of metapristone and mifepristone (2.5, 10, 50 mg/kg/day for 35 days) to melanoma C57BL/6 mouse model showed significant attenuation of pulmonary metastatic development. Oral administration of high doses of metapristone and mifepristone to normal mice for 35 days (25, 100, 250 mg/kg/day) resulted in a dose-dependent increase in mouse liver weight that was more severe with mifepristone than metapristone. The long-term toxicity study revealed more changes by mifepristone in counts of erythrocytes, leukocytes and platelets than by metapristone. In conclusion, metapristone may fit into a new class of cancer metastatic chemopreventive agents. It showed a safety and efficacy profile better than mifepristone. PMID- 26898455 TI - Let-7a mimic attenuates CCL18 induced breast cancer cell metastasis through Lin 28 pathway. AB - BACKGROUND: MicroRNAs are believed to influence breast cancer cell tumorgenicity by interacting with the production of tumor associated macrophages. At this stage, this hypothesis lacks sufficient empirical evidence. Our study is an investigation of the effects of let-7a on the function of human breast cancer cell lines that had undergone chemokine ligand 18 (CCL18) stimulation. METHODS: Two breast cancer cell lines MDA-MB-231 and MCF-7 were transfected with let-7a mimics with or without CCL18 simulation. The expression level of let-7a was evaluated with qRT-PCR. Our study examined cell proliferation, migration and cell cycles following let-7a treatment. The predicted target of let-7a was identified and confirmed in vitro by a dual luciferase reporter system. The associations between let-7a, CCL18 and target gene expression were evaluated using RT-PCR and the Western blotting method. RESULTS: The downregulated expression level of let 7a was observed in both breast cancer cell lines. When compared to the control and CCL18 stimulation groups, cell proliferation and migration in MDA-MB-231 and MCF-7 cells were significantly inhibited by let-7a. Furthermore, the cell cycle was dramatically blocked at the G2/M phase. The luciferase reporter identified Lin28 as the direct binding target of let-7a in both breast cancer cell lines. CONCLUSION: Upregulation of let-7a carries the potential to reverse CCL18 induced cell proliferation and migration alteration in breast cancer cells by regulating Lin28 expression. Our results provided evidence which suggests the use of let-7a as a therapeutic agent in the treatment of breast cancer. PMID- 26898456 TI - 2-Methoxy-5((3,4,5-trimethosyphenyl)seleninyl) phenol (SQ0814061), a novel microtubule inhibitor, evokes G2/M cell cycle arrest and apoptosis in human breast cancer cells. AB - Breast cancer is the leading cause of cancer death in women worldwide, and novel chemotherapeutic drugs with high activity and no drug resistance for treating breast cancer are needed urgently. In this study, we investigated the antitumor effect of 2-methoxy-5((3,4,5-trimethosyphenyl)seleninyl) phenol (SQ0814061), which has a strong inhibition of cell growth in MCF-7 and MDA-MB-231 cells. We demonstrated that SQ0814061 (SQ) time-dependently induced cell cycle arrest at G2/M phase and subsequently progressed into apoptosis, which is associated with microtubule depolymerization. Western blot analysis revealed that up-regulation of cyclin B1 and Aurora A was related with G2/M phase arrest in MCF-7 and MDA-MB 231 cells treatment with SQ. However, the formation of multinucleated cells after a long time exposed to SQ of MCF-7 cells delayed the cell death. In addition, apoptosis induced by SQ is correlated with the down-regulation of the PI3K-Akt MDM2 pathway in MCF-7 and MDA-MB-231 cells. Treatment with the PI3K specific inhibitor, LY294002, increased SQ-induced cell growth inhibitory rate and apoptosis rate of MCF-7 and MDA-MB-231 cells. Moreover, SQ induced MCF-7 and MDA MB-231 cells to generate reactive oxygen species (ROS), and the SQ-induced cell death was ROS dependent. In conclusion, all the data demonstrated that SQ exhibited its antitumor activity through disrupting the microtubule assembly, inducing cell cycle arrest and eventually apoptosis which is associated with PI3K Akt-MDM2 pathway in MCF-7 and MDA-MB-231 cells. Therefore, the novel compound SQ is a promising microtubule inhibitor that has tremendous potentials for therapeutic treatment of human mastocarcinoma. PMID- 26898457 TI - Neuronal apoptosis may not contribute to the long-term cognitive dysfunction induced by a brief exposure to 2% sevoflurane in developing rats. AB - BACKGROUND: Sevoflurane is an inhaled anesthetic commonly used in the pediatric. Recent animal studies suggest that early exposure to high concentration of sevoflurane for a long duration can induce neuroapoptosis and later cognitive dysfunction. However, the neurodevelopmental impact induced by lower concentration and shorter exposure duration of sevoflurane is unclear. To investigate whether early exposure to 2% concentration of sevoflurane for a short duration (clinically relevant usage of sevoflurane) can also induce neuroapoptosis and later cognitive dysfunction. METHODS: Rat pups were subjected to control group, 2% sevoflurane for 3h and 3% sevoflurane for 6h. TUNEL assay and apoptotic enzyme cleaved caspase-3 measured by western blot were used for detection of neuronal apoptosis in frontal cortex and CA1 region of hippocampus 24 after sevoflurane treatment. Long-term cognitive function was evaluated by Morris water maze and passive avoidance test as the rats grew up. RESULTS: The apoptotic levels in frontal cortex and CA1 region were significantly increased after rats exposed to 3% sevoflurane for 6h (P<0.05), but not 2% sevoflurane for 3h (P>0.05). Exposure to both 2% sevoflurane for 3h and 3% sevoflurane for 6h could cause long-term cognitive dysfunction and animals exposed to 3% sevoflurane for 6h exhibited worse neurodevelopmental outcomes (P<0.05). CONCLUSION: It was suggested that neuronal apoptosis might not contribute to long-term cognitive dysfunction induced by 2% concentration and short exposure time of sevoflurane. Our findings also suggested that the mechanisms of sevoflurane-induced neurodevelopmental impact might be various, depending on the concentration and exposure duration. PMID- 26898458 TI - IL-1beta induced RXRalpha overexpression through activation of NF-kappaB signaling in gastric carcinoma. AB - BACKGROUND: Abnormal expression of Retinoid X Receptor alpha (RXRalpha) seems to be a frequent incident in a variety of cancers. However, the expression pattern and the mechanisms in gastric carcinoma (GC) remain unclear. METHODS: In GC tissues and cell lines, the expression levels of RXRalpha mRNA and protein were detected by Q-PCR and Western blot, respectively; the localization of RXRalpha was evaluated by immunohistochemistry (IHC) or immunocytochemistry (ICC). The effect of IL-1beta on RXRalpha expression and localization was detected by Western blot and ICC. Nuclear factor-kappaB (NF-kappaB) pathway was assessed via Western blot. RESULTS: RXRalpha expression was markedly elevated at both mRNA and protein levels in GC tissues and cell lines (all P<0.05). The abnormal overexpression of RXRalpha was predominantly visualized in cytoplasm. IL-1beta significantly induced cytoplasmic expression of RXRalpha in a time-dependent manner. Co-incubation with IL-1beta enhanced phospho-IKKalpha (p-IKKalpha) expression and this effect could be inhibited by the specific inhibitor for NF kappaB (all P<0.01). CONCLUSIONS: IL-1beta upregulated RXRalpha through activation of NF-kappaB signaling and these suggested a possible clinic significance of retinoid receptor expression in the diagnosis and treatment of GC. PMID- 26898461 TI - Erratum: Quantitative functional characterization of conserved molecular interactions in the active site of mannitol 2-dehydrogenase. PMID- 26898459 TI - Mutation R273H confers p53 a stimulating effect on the IGF-1R-AKT pathway via miR 30a suppression in breast cancer. AB - p53 is the most highly mutated tumor suppressor in human malignancies. A wide array of p53 mutations has been revealed to play pivotal roles during cancer progression, which abolish anti-tumor functions of wild type p53 but also elicit tumorigenic effects by activating a diverse subset of downstream molecules. R273H mutation of p53 has been closely implicated in human cancer. Here we report miR 30a as a novel downstream target of p53 R273H mutant, which binds to the promoter region to repress miR-30a expression. Consequently, p53 R273H mutant enhances the migratory capabilities of tumor cells that are compromised by exogenous miR-30a over-expression. Our further investigation indicates that p53 R273H mutation unleashes the inhibition effect of miR-30a on IGF-1R expression, thus leading to elevated activation of IGF-1R-AKT signaling cascade in tumor cells. PMID- 26898462 TI - Rounded Cu2ZnSnS4 nanosheet networks as a cost-effective counter electrode for high-efficiency dye-sensitized solar cells. AB - Semi-transparent rounded Cu2ZnSnS4 (CZTS) nanosheet networks were in situ grown on a FTO glass substrate, via an effective solution method, without any post treatments. An improved power conversion efficiency of 6.24% was obtained by applying CZTS nanosheet networks as a counter electrode for dye-sensitized solar cells. When assisted by a mirror reflection, the PCE increased to 7.12%. PMID- 26898463 TI - Extracellular Reactive Oxygen Species Drive Apoptosis-Induced Proliferation via Drosophila Macrophages. AB - Apoptosis-induced proliferation (AiP) is a compensatory mechanism to maintain tissue size and morphology following unexpected cell loss during normal development, and may also be a contributing factor to cancer and drug resistance. In apoptotic cells, caspase-initiated signaling cascades lead to the downstream production of mitogenic factors and the proliferation of neighboring surviving cells. In epithelial cells of Drosophila imaginal discs, the Caspase-9 ortholog Dronc drives AiP via activation of Jun N-terminal kinase (JNK); however, the specific mechanisms of JNK activation remain unknown. Here we show that caspase induced activation of JNK during AiP depends on an inflammatory response. This is mediated by extracellular reactive oxygen species (ROSs) generated by the NADPH oxidase Duox in epithelial disc cells. Extracellular ROSs activate Drosophila macrophages (hemocytes), which in turn trigger JNK activity in epithelial cells by signaling through the tumor necrosis factor (TNF) ortholog Eiger. We propose that in an immortalized ("undead") model of AiP, signaling back and forth between epithelial disc cells and hemocytes by extracellular ROSs and TNF/Eiger drives overgrowth of the disc epithelium. These data illustrate a bidirectional cell cell communication pathway with implication for tissue repair, regeneration, and cancer. PMID- 26898464 TI - Hippocampal Sharp-Wave Ripples Influence Selective Activation of the Default Mode Network. AB - The default mode network (DMN) is a commonly observed resting-state network (RSN) that includes medial temporal, parietal, and prefrontal regions involved in episodic memory [1-3]. The behavioral relevance of endogenous DMN activity remains elusive, despite an emerging literature correlating resting fMRI fluctuations with memory performance [4, 5]-particularly in DMN regions [6-8]. Mechanistic support for the DMN's role in memory consolidation might come from investigation of large deflections (sharp-waves) in the hippocampal local field potential that co-occur with high-frequency (>80 Hz) oscillations called ripples both during sleep [9, 10] and awake deliberative periods [11-13]. Ripples are ideally suited for memory consolidation [14, 15], since the reactivation of hippocampal place cell ensembles occurs during ripples [16-19]. Moreover, the number of ripples after learning predicts subsequent memory performance in rodents [20-22] and humans [23], whereas electrical stimulation of the hippocampus after learning interferes with memory consolidation [24-26]. A recent study in macaques showed diffuse fMRI neocortical activation and subcortical deactivation specifically after ripples [27]. Yet it is unclear whether ripples and other hippocampal neural events influence endogenous fluctuations in specific RSNs-like the DMN-unitarily. Here, we examine fMRI datasets from anesthetized monkeys with simultaneous hippocampal electrophysiology recordings, where we observe a dramatic increase in the DMN fMRI signal following ripples, but not following other hippocampal electrophysiological events. Crucially, we find increases in ongoing DMN activity after ripples, but not in other RSNs. Our results relate endogenous DMN fluctuations to hippocampal ripples, thereby linking network-level resting fMRI fluctuations with behaviorally relevant circuit-level neural dynamics. PMID- 26898466 TI - A Rapid Tactile-Motor Reflex Automatically Guides Reaching toward Handheld Objects. AB - The ability to respond quickly and effectively when objects in the world suddenly change position is essential for skilled action, and previous work has documented how unexpected changes in the location of a visually presented target during reaching can elicit rapid reflexive (i.e., automatic) corrections of the hand's trajectory [1-12]. In object manipulation and tool use, the sense of touch can also provide information about changes in the location of reach targets. Consider the many tasks where we reach with one hand to part of an object grasped by the other hand: reaching to a berry while holding a branch, reaching for a cap while grasping a bottle, and reaching toward a dog's collar while holding the dog's leash. In such cases, changes in the position of the reach target, due to wind, slip, or an active agent, can be detected, in principle, through touch. Here, we show that when people reach with their right hand to a target attached to the far end of a rod contacted, at the near end, by their left hand, an unexpected change in target location caused by rod rotation rapidly evokes an effective reach correction. That is, spatial information about a change in target location provided by tactile inputs to one hand elicits a rapid correction of the other hand's trajectory. In addition to uncovering a tactile-motor reflex that can support manipulatory actions, our results demonstrate that automatic reach corrections to moving targets are not unique to visually registered changes in target location. PMID- 26898465 TI - The Breakdown of Stored Triacylglycerols Is Required during Light-Induced Stomatal Opening. AB - Stomata regulate the uptake of CO2 and the loss of water vapor [1] and contribute to the control of water-use efficiency [2] in plants. Although the guard-cell signaling pathway coupling blue light perception to ion channel activity is relatively well understood [3], we know less about the sources of ATP required to drive K(+) uptake [3-6]. Here, we show that triacylglycerols (TAGs), present in Arabidopsis guard cells as lipid droplets (LDs), are involved in light-induced stomatal opening. Illumination induces reductions in LD abundance, and this involves the PHOT1 and PHOT2 blue light receptors [3]. Light also induces decreases in specific TAG molecular species. We hypothesized that TAG-derived fatty acids are metabolized by peroxisomal beta-oxidation to produce ATP required for stomatal opening. In silico analysis revealed that guard cells express all the genes required for beta-oxidation, and we showed that light-induced stomatal opening is delayed in three TAG catabolism mutants (sdp1, pxa1, and cgi-58) and in stomata treated with a TAG breakdown inhibitor. We reasoned that, if ATP supply was delaying light-induced stomatal opening, then the activity of the plasma membrane H(+)-ATPase should be reduced at this time. Monitoring changes in apoplastic pH in the mutants showed that this was the case. Together, our results reveal a new role for TAGs in vegetative tissue and show that PHOT1 and PHOT2 are involved in reductions in LD abundance. Reductions in LD abundance in guard cells of the lycophyte Selaginella suggest that TAG breakdown may represent an evolutionarily conserved mechanism in light-induced stomatal opening. PMID- 26898467 TI - AtMic60 Is Involved in Plant Mitochondria Lipid Trafficking and Is Part of a Large Complex. AB - The mitochondrion is an organelle originating from an endosymbiotic event and playing a role in several fundamental processes such as energy production, metabolite syntheses, and programmed cell death. This organelle is delineated by two membranes whose synthesis requires an extensive exchange of phospholipids with other cellular organelles such as endoplasmic reticulum (ER) and vacuolar membranes in yeast. These transfers of phospholipids are thought to occur by a non-vesicular pathway at contact sites between two closely apposed membranes. In plants, little is known about the biogenesis of mitochondrial membranes. Contact sites between ER and mitochondria are suspected to play a similar role in phospholipid trafficking as in yeast, but this has never been demonstrated. In contrast, it has been shown that plastids are able to transfer lipids to mitochondria during phosphate starvation. However, the proteins involved in such transfer are still unknown. Here, we identified in Arabidopsis thaliana a large lipid-enriched complex called the mitochondrial transmembrane lipoprotein (MTL) complex. The MTL complex contains proteins located in the two mitochondrial membranes and conserved in all eukaryotic cells, such as the TOM complex and AtMic60, a component of the MICOS complex. We demonstrate that AtMic60 contributes to the export of phosphatidylethanolamine from mitochondria and the import of galactoglycerolipids from plastids during phosphate starvation. Furthermore, AtMic60 promotes lipid desorption from membranes, likely as an initial step for lipid transfer, and binds to Tom40, suggesting that AtMic60 could regulate the tethering between the inner and outer membranes of mitochondria. PMID- 26898468 TI - Architecture and Connectivity Govern Actin Network Contractility. AB - Actomyosin contractility plays a central role in a wide range of cellular processes, including the establishment of cell polarity, cell migration, tissue integrity, and morphogenesis during development. The contractile response is variable and depends on actomyosin network architecture and biochemical composition. To determine how this coupling regulates actomyosin-driven contraction, we used a micropatterning method that enables the spatial control of actin assembly. We generated a variety of actin templates and measured how defined actin structures respond to myosin-induced forces. We found that the same actin filament crosslinkers either enhance or inhibit the contractility of a network, depending on the organization of actin within the network. Numerical simulations unified the roles of actin filament branching and crosslinking during actomyosin contraction. Specifically, we introduce the concept of "network connectivity" and show that the contractions of distinct actin architectures are described by the same master curve when considering their degree of connectivity. This makes it possible to predict the dynamic response of defined actin structures to transient changes in connectivity. We propose that, depending on the connectivity and the architecture, network contraction is dominated by either sarcomeric-like or buckling mechanisms. More generally, this study reveals how actin network contractility depends on its architecture under a defined set of biochemical conditions. PMID- 26898470 TI - Coercion Changes the Sense of Agency in the Human Brain. AB - People may deny responsibility for negative consequences of their actions by claiming that they were "only obeying orders." The "Nuremberg defense" offers one extreme example, though it is often dismissed as merely an attempt to avoid responsibility. Milgram's classic laboratory studies reported widespread obedience to an instruction to harm, suggesting that social coercion may alter mechanisms of voluntary agency, and hence abolish the normal experience of being in control of one's own actions. However, Milgram's and other studies relied on dissembling and on explicit measures of agency, which are known to be biased by social norms. Here, we combined coercive instructions to administer harm to a co participant, with implicit measures of sense of agency, based on perceived compression of time intervals between voluntary actions and their outcomes, and with electrophysiological recordings. In two experiments, an experimenter ordered a volunteer to make a key-press action that caused either financial penalty or demonstrably painful electric shock to their co-participant, thereby increasing their own financial gain. Coercion increased the perceived interval between action and outcome, relative to a situation where participants freely chose to inflict the same harms. Interestingly, coercion also reduced the neural processing of the outcomes of one's own action. Thus, people who obey orders may subjectively experience their actions as closer to passive movements than fully voluntary actions. Our results highlight the complex relation between the brain mechanisms that generate the subjective experience of voluntary actions and social constructs, such as responsibility. PMID- 26898469 TI - Chromosome Cohesion Established by Rec8-Cohesin in Fetal Oocytes Is Maintained without Detectable Turnover in Oocytes Arrested for Months in Mice. AB - Sister chromatid cohesion mediated by the cohesin complex is essential for chromosome segregation in mitosis and meiosis [1]. Rec8-containing cohesin, bound to Smc3/Smc1alpha or Smc3/Smc1beta, maintains bivalent cohesion in mammalian meiosis [2-6]. In females, meiotic DNA replication and recombination occur in fetal oocytes. After birth, oocytes arrest at the prolonged dictyate stage until recruited to grow into mature oocytes that divide at ovulation. How cohesion is maintained in arrested oocytes remains a pivotal question relevant to maternal age-related aneuploidy. Hypothetically, cohesin turnover regenerates cohesion in oocytes. Evidence for post-replicative cohesion establishment mechanism exists, in yeast and invertebrates [7, 8]. In mouse fetal oocytes, cohesin loading factor Nipbl/Scc2 localizes to chromosome axes during recombination [9, 10]. Alternatively, cohesion is maintained without turnover. Consistent with this, cohesion maintenance does not require Smc1beta transcription, but unlike Rec8, Smc1beta is not required for establishing bivalent cohesion [11, 12]. Rec8 maintains cohesion without turnover during weeks of oocyte growth [3]. Whether the same applies to months or decades of arrest is unknown. Here, we test whether Rec8 activated in arrested mouse oocytes builds cohesion revealed by TEV cleavage and live-cell imaging. Rec8 establishes cohesion when activated during DNA replication in fetal oocytes using tamoxifen-inducible Cre. In contrast, no new cohesion is detected when Rec8 is activated in arrested oocytes by tamoxifen despite cohesin synthesis. We conclude that cohesion established in fetal oocytes is maintained for months without detectable turnover in dictyate-arrested oocytes. This implies that women's fertility depends on the longevity of cohesin proteins that established cohesion in utero. PMID- 26898471 TI - Tissue Crowding Induces Caspase-Dependent Competition for Space. AB - Regulation of tissue size requires fine tuning at the single-cell level of proliferation rate, cell volume, and cell death. Whereas the adjustment of proliferation and growth has been widely studied [1-5], the contribution of cell death and its adjustment to tissue-scale parameters have been so far much less explored. Recently, it was shown that epithelial cells could be eliminated by live-cell delamination in response to an increase of cell density [6]. Cell delamination was supposed to occur independently of caspase activation and was suggested to be based on a gradual and spontaneous disappearance of junctions in the delaminating cells [6]. Studying the elimination of cells in the midline region of the Drosophila pupal notum, we found that, contrary to what was suggested before, Caspase 3 activation precedes and is required for cell delamination. Yet, using particle image velocimetry, genetics, and laser-induced perturbations, we confirmed [6] that local tissue crowding is necessary and sufficient to drive cell elimination and that cell elimination is independent of known fitness-dependent competition pathways [7-9]. Accordingly, activation of the oncogene Ras in clones was sufficient to compress the neighboring tissue and eliminate cells up to several cell diameters away from the clones. Mechanical stress has been previously proposed to contribute to cell competition [10, 11]. These results provide the first experimental evidences that crowding-induced death could be an alternative mode of super-competition, namely mechanical super competition, independent of known fitness markers [7-9], that could promote tumor growth. PMID- 26898472 TI - The Timing of Midzone Stabilization during Cytokinesis Depends on Myosin II Activity and an Interaction between INCENP and Actin. AB - The final steps of cell division are tightly coordinated in space and time, but whether mechanisms exist to couple the actin and microtubule (MT) cytoskeletons during anaphase and cytokinesis (C phase) is largely unknown. During anaphase, MTs are incorporated into an anti-parallel array termed the spindle midzone (midzone MTs), whereas F-actin and non-muscle myosin II, together with other factors, organize into the cleavage furrow [1]. Previous studies in somatic cells have shown that midzone MTs become highly stable after furrows have begun ingression [2], indicating that furrow-to-MT communication may occur. Midzone formation is also inhibited in fly spermatocytes that fail to form a cleavage furrow [3] and during monopolar cytokinesis when myosin contractility is blocked by blebbistatin [4]. We show here that midzone MT stabilization is dependent on actomyosin contraction, suggesting that there is active coordination between furrow ingression and microtubule dynamics. Midzone microtubule stabilization also depends on the kinase activity of Aurora B, the catalytic subunit of the chromosomal passenger complex (CPC), uncovering a feedback mechanism that couples furrowing with microtubule dynamics. We further show that the CPC scaffolding protein INCENP (inner centromere protein) binds actin, an interaction that is important for cytokinesis and for midzone MT stabilization following furrow ingression. Stabilization of midzone MTs with low amounts of Taxol rescues cytokinesis in INCENP actin-binding mutant-expressing cells. Collectively, our work demonstrates that the actin and microtubule cytoskeletons are coordinated during cytokinesis and suggests that the CPC is integral for coupling furrow ingression with midzone microtubule stabilization. PMID- 26898473 TI - Interactive effects between gaze direction and facial expression on attentional resources deployment: the task instruction and context matter. AB - In three experiments, we tested whether the amount of attentional resources needed to process a face displaying neutral/angry/fearful facial expressions with direct or averted gaze depends on task instructions, and face presentation. To this end, we used a Rapid Serial Visual Presentation paradigm in which participants in Experiment 1 were first explicitly asked to discriminate whether the expression of a target face (T1) with direct or averted gaze was angry or neutral, and then to judge the orientation of a landscape (T2). Experiment 2 was identical to Experiment 1 except that participants had to discriminate the gender of the face of T1 and fearful faces were also presented randomly inter-mixed within each block of trials. Experiment 3 differed from Experiment 2 only because angry and fearful faces were never presented within the same block. The findings indicated that the presence of the attentional blink (AB) for face stimuli depends on specific combinations of gaze direction and emotional facial expressions and crucially revealed that the contextual factors (e.g., explicit instruction to process the facial expression and the presence of other emotional faces) can modify and even reverse the AB, suggesting a flexible and more contextualized deployment of attentional resources in face processing. PMID- 26898475 TI - Mechanical characterization of the P56 mouse brain under large-deformation dynamic indentation. AB - The brain is a complex organ made up of many different functional and structural regions consisting of different types of cells such as neurons and glia, as well as complex anatomical geometries. It is hypothesized that the different regions of the brain exhibit significantly different mechanical properties, which may be attributed to the diversity of cells and anisotropy of neuronal fibers within individual brain regions. The regional dynamic mechanical properties of P56 mouse brain tissue in vitro and in situ at velocities of 0.71-4.28 mm/s, up to a deformation of 70 MUm are presented and discussed in the context of traumatic brain injury. The experimental data obtained from micro-indentation measurements were fit to three hyperelastic material models using the inverse Finite Element method. The cerebral cortex elicited a stiffer response than the cerebellum, thalamus, and medulla oblongata regions for all velocities. The thalamus was found to be the least sensitive to changes in velocity, and the medulla oblongata was most compliant. The results show that different regions of the mouse brain possess significantly different mechanical properties, and a significant difference also exists between the in vitro and in situ brain. PMID- 26898474 TI - Association of the apparent diffusion coefficient with maturity in adolescent sacroiliac joints. AB - PURPOSE: To determine the extent to which apparent diffusion coefficient (ADC) values vary with skeletal maturity in adolescent joints. MATERIALS AND METHODS: A retrospective study was performed with Institutional Review Board (IRB) approval. We used a picture archiving and communication system (PACS) search to identify and recruit all adolescents who had undergone 1.5T magnetic resonance imaging (MRI) of the sacroiliac joints (SIJs) between January 2010 and June 2015, and had no evidence of sacroiliitis and normal inflammatory markers. In all, 55 individuals were assessed. For each patient, coronal and sagittal images of the sacrum were visually analyzed to determine sacral maturity. Patients were divided into three groups depending on the degree of fusion of the sacral segmental apophyses: "Fused," "Partial," and "Unfused." For each group, SIJ ADC was measured using a linear region-of-interest technique. RESULTS: Mean ADC values were 690 * 10(-6) mm(2) /s in the fused group, 720 * 10(-6) mm(2) /s in the partial group, and 842 * 10(-6) mm(2) /s in the unfused group. ADC values were significantly higher in the unfused group than in the fused group (P = 0.046). ADC values were also higher in unfused subjects than partially fused subjects (P = 0.074). CONCLUSION: Joint ADC values are higher in skeletally immature (unfused) patients than in skeletally more mature (fused) patients. ADC values measured in the unfused group overlap with those previously reported in sacroiliitis. These results suggest that ADC measurements in adolescent joints must be interpreted in light of joint maturity. Joint immaturity may lead to misdiagnosis of sacroiliitis, since immature juxta-articular bone may appear similar to inflammation. J. Magn. Reson. Imaging 2016. J. Magn. Reson. Imaging 2016;44:556-564. PMID- 26898476 TI - Application of self-sustaining smouldering combustion for the destruction of wastewater biosolids. AB - Managing biosolids, the major by-product from wastewater treatment plants (WWTPs), persists as a widespread challenge that often constitutes the majority of WWTP operating costs. Self-sustained smouldering combustion is a new approach for organic waste treatment, in which the waste - the combustion fuel - is destroyed in an energy efficient manner after mixing it with sand. Smouldering has never been applied to biosolids. Column experiments, using biosolids obtained from a WWTP, were employed to identify if, and under what conditions, smouldering could be used for treating biosolids. The parameter space in which smouldering was self-sustaining was mapped as a function of key system metrics: (1) sand/biosolids mass fraction, (2) biosolids moisture content, and (3) forced air flux. It was found that a self-sustaining reaction is achievable using biosolids with water content as high as 80% (with a biosolids lower heating value greater than 1.6 kJ/g). Moreover, results suggest that operator-controlled air flux can assist in keeping the reaction self-sustaining in response to fluctuations in biosolids properties. This proof-of-concept demonstrates the potential for smouldering as a new energy efficient biosolids disposal method for very wet (i.e., minimally processed) biosolids that may offer WWTPs significant operating cost savings. This study emphasizes smouldering's usefulness as a novel waste management technique. PMID- 26898477 TI - Municipal waste stabilization in a reactor with an integrated active and passive aeration system. AB - To test whether an integrated passive and active aeration system could be an effective solution for aerobic decomposition of municipal waste in technical conditions, a full-scale composting reactor was designed. The waste was actively aerated for 5d, passively aerated for 35 d, and then actively aerated for 5d, and the entire composting process was monitored. During the 45-day observation period, changes in the fractional, morphological and physico-chemical characteristics of the waste at the top of the reactor differed from those in the center of the reactor. The fractional and morphological analysis made during the entire process of stabilization, showed the total reduction of organic matter measured of 82 wt% and 86 wt% at the respective depths. The reduction of organic matter calculated using the results of Lost of Ignition (LOI) and Total Organic Carbon (TOC) showed, respectively, 40.51-46.62% organic matter loss at the top and 45.33-53.39% in the center of the reactor. At the end of the process, moisture content, LOI and TOC at the top were 3.29%, 6.10% and 4.13% higher, respectively, than in the center. The results showed that application of passive aeration in larger scale simultaneously allows the thermophilic levels to be maintained during municipal solid waste composting process while not inhibiting microbial activity in the reactor. PMID- 26898478 TI - Life cycle assessment of hybrid vehicles recycling: Comparison of three business lines of dismantling. AB - This paper undertakes an environmental evaluation of hybrid vehicles recycling, using industrial data from Comet Traitement SA in Belgium. Three business lines have been modelled and analysed. The first one is relative to the business as usual with a dismantling to recover batteries and engines followed by shredding and post shredding treatments. The second one considers, in addition, the removal of electronic control units (ECU) before shredding followed by same steps than in the first line and the last one is relative to the additional removal of big plastic parts before shredding and business as usual post shredding treatments. Results show non-significant environmental benefits when ECU or large parts of plastics are recovered before shredding. Improvements in terms of environmental benefits are lower than the uncertainty of the results. Indeed, the performing usual process for end-of-life vehicles (ELV) treatment reaches 97% of the ELV which is valorised in terms of metal and energy recoveries. Post shredding treatment units include metals, plastics and energy recovery of residues. Comet business as usual route for ELV valorisation is in accordance with the requirements of the European directive and recommendations for further improvement with dismantling of other parts (ECU or plastics) before shredding are non-relevant in this case. PMID- 26898480 TI - Comparison of goniometric measurements of the stifle joint in seven breeds of normal dogs. AB - OBJECTIVE: To compare the goniometric measurements of the stifle joint in seven dog breeds, and to determine the relationship among goniometric measurements, age, body weight, tibial plateau angle, crus and thigh circumferences, and widths of quadriceps, hamstring, and gastrocnemius muscles in healthy dogs. METHODS: We used a total of 126 dogs from seven different breeds, and recorded the angle of the stifle joint at standing, extension, and flexion together with the range of motion (ROM). The circumferences of the thigh and crus were also measured. Mediolateral radiographic projections of the tibia and the femur were obtained from the dogs, and the tibial plateau angles, as well as the widths of quadriceps, hamstring, and gastrocnemius muscles, were measured from these images. RESULTS: Neither the sex of the dog nor the differences in the side measured affected the goniometric measurements of the stifle joint. The standing, extension, flexion, and ROM angles were different among the breeds. The standard deviations of the standing and extension angles were small relative to their means, but the standard deviations of the flexion angle were large relative to their means in all breeds. Body weight and muscular measurements were the most influential factors on the stifle flexion angle and ROM. CLINICAL SIGNIFICANCE: Breed differences, body weights, and muscle mass should be taken into consideration during assessment of the stifle function using goniometric measurements. PMID- 26898482 TI - An unusual cause of chronic headache in a young man. PMID- 26898481 TI - Hepatitis B core-related antigen levels are associated with response to entecavir and peginterferon add-on therapy in hepatitis B e antigen-positive chronic hepatitis B patients. AB - Hepatitis B core-related antigen (HBcrAg), a new serum marker, may be useful in monitoring chronic hepatitis B infection. HBcrAg was measured in 175 hepatitis B e antigen-positive patients treated with entecavir (ETV) with or without peginterferon (PEG-IFN) add-on therapy. Decline in HBcrAg was stronger in patients with vs. without combined response (ETV: -3.22 vs. -1.71 log U/mL, p <0.001; PEG-IFN add-on: -3.16 vs. -1.83 IU/mL, p <0.001) and in patients with vs. without hepatitis B surface antigen (HBsAg) response (ETV: -2.60 vs. -1.74 log U/mL, p <0.001; PEG-IFN add-on: -2.38 vs. -2.15 log U/mL, p = 0.31). HBcrAg was associated with combined response (adjusted odds ratio 0.3, 95% confidence interval 0.2-0.5, p <0.001), but was not superior to quantitative HBsAg (qHBsAg). PMID- 26898485 TI - Erratum. PMID- 26898483 TI - Chronic Migraine with Medication Overuse and OnabotulinumtoxinA: Two Positive Case Reports of a Modified Injection Protocol. PMID- 26898484 TI - Calcitonin Gene-Related Peptide Targeted Therapy for Migraine. PMID- 26898479 TI - SGT1 is required in PcINF1/SRC2-1 induced pepper defense response by interacting with SRC2-1. AB - PcINF1 was previously found to induce pepper defense response by interacting with SRC2-1, but the underlying mechanism remains uninvestigated. Herein, we describe the involvement of SGT1 in the PcINF1/SRC2-1-induced immunity. SGT1 was observed to be up-regulated by Phytophthora capsici inoculation and synergistically transient overexpression of PcINF1/SRC2-1 in pepper plants. SGT1-silencing compromised HR cell death, blocked H2O2 accumulation, and downregulated HR associated and hormones-dependent marker genes' expression triggered by PcINF1/SRC2-1 co-overexpression. The interaction between SRC2-1 and SGT1 was found by the yeast two hybrid system and was further confirmed by bimolecular fluorescence complementation and co-immunoprecipitation analyses. The SGT1/SRC2-1 interaction was enhanced by transient overexpression of PcINF1 and Phytophthora capsici inoculation, and SGT1-silencing attenuated PcINF1/SRC2-1 interaction. Additionally, by modulating subcellular localizations of SRC2-1, SGT1, and the interacting complex of SGT1/SRC2-1, it was revealed that exclusive nuclear targeting of the SGT1/SRC2-1 complex blocks immunity triggered by formation of SGT1/SRC2-1, and a translocation of the SGT1/SRC2-1 complex from the plasma membrane and cytoplasm to the nuclei upon the inoculation of P. capsici. Our data demonstrate that the SGT1/SRC2-1 interaction, and its nucleocytoplasmic partitioning, is involved in pepper's immunity against P. capsici, thus providing a molecular link between Ca(2+) signaling associated SRC2-1 and SGT1-mediated defense signaling. PMID- 26898486 TI - Pain assessment in rheumatology - How can we do better? A literature review. AB - Patients' symptoms have a place of prominence in the rheumatology landscape, and among them pain is the most conspicuous. Several pain assessment tools have been validated. One-dimensional pain scales such as visual analog scales (VASs) and numeric rating scales (NRSs) are fast to administer but have limitations that must be acknowledged. Some clinical situations require the use of multidimensional scales such as the McGill Pain Questionnaire or the Multidimensional Pain Inventory (MPI). These tools allow the assessment and management of the diverse components of pain. Here, we review the main patient reported outcomes that can serve to evaluate pain and the psychometric properties of pain assessment tools. We also discuss the selection of the tool most appropriate for each situation (e.g., everyday practice and research). PMID- 26898487 TI - Intraoperative Flow Measurement by Microflow Probe During Spinal Dural Arteriovenous Fistula Surgery. AB - OBJECTIVE: Flow measurement by microvascular ultrasonic flow probe is an established procedure in intracranial vascular surgery. This study tested the application of this procedure in spinal dural arteriovenous fistula (SDAVF) treatment. METHODS: Data from 12 SDAVF patients who consecutively underwent microsurgical resection with the assistance of both microflow probe and indocyanine green videoangiography (ICG-VA) were retrospectively analyzed. Flowmetry was performed on a dilated perimedullary venous plexus at different distances from the fistula point (FP). In addition, measurements were made at different phases of surgery to address specific issues: at the beginning, to identify the fistula; after temporary clipping, to evaluate proper disconnection; and after section, to exclude residual filling. RESULTS: Flowmetry was reliable in assessing both the value and direction of flow in all cases, thereby aiding fistula localization and confirming its disconnection. Indeed, fistula localization was helped by detection of increasing flow values approaching the FP (mean flow: 11 mL/min <10 mm vs. 3 mL/min >20 mm), while fistula disconnection was confirmed by a flow value lower than 1 mL/min (0-1 mL/min). Data from microflow probe measurements were concordant with ICG-VA data in all cases. In 3 cases, ICG-VA findings on fistula disconnection uncertain due to residual ICG dye were clarified by flowmetry. CONCLUSIONS: With the limits of our small series, multistage intraoperative quantitative flow measurement is a feasible, safe, and reliable adjunct in the surgical treatment of SDAVFs. The procedure provides data helpful in guiding the surgical strategy or clarifying ICG-VA data when necessary. PMID- 26898489 TI - Can Adherence to Traumatic Brain Injury Guidelines Move the Needle in India and Beyond? PMID- 26898488 TI - Treatment and Outcome in 65 Children with Optic Pathway Gliomas. AB - INTRODUCTION: Optic pathway gliomas (OPGs) are rare neoplasms in children with an unpredictable clinical course. There is significant controversy regarding the optimal management and outcome of these patients. METHODS: Charts of all patients with OPG diagnosed and treated at Children's Cancer Hospital Egypt between July 2007 and July 2014 were retrospectively reviewed. We evaluated the roles of surgical, ophthalmologic, endocrinologic, neurologic, and treatment aspects of care. RESULTS: Sixty-five patients were included in this study, with a mean age of 5.3 years. OPGs were chiasmatic (n = 25), optic nerve (n = 18), hypothalamic (n = 7), and chiasmatic/hypothalamic (n = 7). Extensive involvement of the optic pathway was seen in an additional 8 patients. Twenty cases had neurofibromatosis type 1. Four cases underwent surgical debulking, and 28 were biopsied (16 open, 11 stereotactic, and 1 endoscopic). Nine of the 18 optic nerve tumors were managed by total excision. Twenty-four patients did not undergo any surgical intervention. Forty-five patients received chemotherapy. Histopathology revealed pilocytic (n = 20), pilomyxoid (n = 15), fibrillary astrocytoma (n = 4), and grade I papillary-glioneuronal tumor (n = 1). Nonrepresentative sample (n = 1). The 4-year overall survival rate was 86.3% with mean follow-up period of 32.2 months. CONCLUSION: The initial role of surgery in newly developed OPG is biopsy for tissue diagnosis and relief of the hydrocephalus, if present, followed by chemotherapy. Chemotherapy decreases or stabilizes the tumor size in most cases, leading to preservation of both visual and endocrinal functions. The most significant prognostic factor confirmed in this study was the age of the patient. PMID- 26898490 TI - Impact of Early Leukocytosis and Elevated High-Sensitivity C-Reactive Protein on Delayed Cerebral Ischemia and Neurologic Outcome After Subarachnoid Hemorrhage. AB - BACKGROUND: The role of inflammatory response in the pathophysiology of subarachnoid hemorrhage (SAH) is being increasingly recognized. This study analyzed the impact of cellular and biochemical markers of early inflammatory response to ictus on outcome after SAH. METHODS: Patients with SAH were prospectively studied for markers of early cellular, biochemical, and cytotoxic inflammatory response, including total leukocyte count (TLC), high-sensitivity C reactive protein (hs-CRP), and lactate dehydrogenase. The relationship of these markers to delayed cerebral ischemia (DCI), new infarct, and Glasgow Outcome Scale (GOS) score at 3 months was studied. RESULTS: The study comprised 246 patients. Of patients, 94 who developed DCI had a significantly higher TLC [+/- SD] (11.2 * 10(3)/mm(3) [+/- 4.0] vs. 9.4 * 10(3)/mm(3) [+/- 2.9], P = 0.001) and 62 with new infarct had significantly higher TLC (11.0 * 10(3)/mm(3) [+/- 3.6] vs. 9.8 * 10(3)/mm(3) [+/- 3.4], P = 0.05). GOS score had a significant inverse relationship to TLC at admission. The mean TLC [+/- SD] was 12.7 * 10(3)/mm(3) [+/- 4.2], 11.7 * 10(3)/mm(3) [+/- 3.1], 10.2 * 10(3)/mm(3) [+/- 3.4], and 9.3 * 10(3)/mm(3) [+/- 2.8] among patients with GOS scores of 1, 3, 4, and 5 (P < 0.001). hs-CRP showed a trend of an inverse relationship to GOS score in univariate analysis. Lactate dehydrogenase had no relationship with any outcome parameter. In multivariate analysis, higher admission TLC had a significant association with DCI (P = 0.01) and poorer GOS score (P < 0.001), and higher hs CRP had a significant association with poorer GOS score (P = 0.05). CONCLUSIONS: A leukocytosis response to ictus seems to have a significant independent association with both DCI and poor GOS score, and hs-CRP level had a significant independent association with poor GOS score, indicating preeminence of early cellular response in SAH pathophysiology. PMID- 26898491 TI - Rectal Manometric Findings and Associated Clinical Changes in Myelopathy from Extradural Spine Pathology. AB - OBJECTIVE: Studies of rectal manometric findings in patients with extradural spine diseases are lacking. The objective of this study was to determine the changes in anorectal physiology caused by myelopathy from extradural spine diseases and to correlate these with other clinical features of myelopathy and improvement after surgery. METHODS: Twenty-eight patients with myelopathy caused by extradural spine diseases were prospectively enrolled and underwent clinical evaluation. Laboratory evaluation included rectal manometry and balloon expulsion tests in each of these patients, as well as pulmonary function tests and uroflowmetry. Follow-up data at 6 weeks were noted. Using the Kruskal-Wallis/Mann Whitney U test and bivariate correlation, an association of manometric parameters with clinical variables and improvement in bowel function after surgery was identified. RESULTS: Squeeze pressure (mean, 92.3 mm Hg) was lower and basal pressures (mean, 76.5 mm Hg) and sphincter pressures at defecation (mean, 92.3 mm Hg) and first sensation (mean, 48.2 mL) were found to be higher than normal. A significant correlation of pulmonary function test (P = 0.01)/uroflowmetry (P = 0.01) parameters and the duration of symptoms (P = 0.02) with manometric parameters was found. Improvement in constipation (P = 0.04) and myelopathy (P = 0.007) were also found to be associated with manometric parameters. CONCLUSIONS: The findings of manometry help explain the cause of constipation in this subset of patients. There was a definite association of manometric parameters with clinical and pulmonary function test/uroflowmetry variables. Few manometric variables were found to be associated with improvement in myelopathy and bowel function. PMID- 26898492 TI - Oculomotor Nerve Palsy Complicates Third Ventricle Colloid Cyst Endoscopic Removal: Case Report. AB - BACKGROUND: A colloid cyst is a rare benign tumor. If indicated, surgical treatment can be realized using a microsurgical technique or an endoscopic technique. We report an uncommon complication of a third ventricle colloid cyst endoscopic removal. CASE DESCRIPTION: The cyst was incidentally discovered on computed tomography scan workup for mild head trauma in a 20-year-old male. Minor headache and minor memory loss were noted on clinical examination. Magnetic resonance imaging workup revealed obstructive hydrocephaly of the lateral ventricles associated with left uncal herniation. Surgery was uneventful. However, left oculomotor palsy was noted postoperatively. Workup revealed oculomotor nerve injury and isolated left mammillary body ischemia, secondary to worsened uncal herniation. This worsening might be caused by acute left ventricle hydrocephaly ascribed to interventricular foramen obstruction during cyst removal. CONCLUSION: Therefore, in similar presentation, realizing septum fenestration before cyst removal should relieve the pressure in the lateral ventricles thus decreasing the risk of herniation. PMID- 26898493 TI - An Experimental Study of Histopathologic Effects of Hemostatic Agents Used in Spinal Surgery. AB - OBJECTIVE: To evaluate and compare the histopathologic effects of various hemostatic agents used in spinal surgery on an experimental laminectomy model in rats. METHODS: There were 110 rats randomly allocated into 11 groups, including sham, control, AnkaferdBlood Stopper (herbal hemostatic), SeraSeal (agar and bovine factor proteins), FLOSEAL (gelatin granules and thrombin), SURGIFLO (gelatin paste), HELITENE (absorbable collagen), Beriplast (fibrin sealant containing fibrinogen, factor XIII, and thrombin), TISSEEL (fibrin sealant), BLOODCARE (hemostatic powder), and SURGICEL (oxidized cellulose polymer) groups. Hemostatic agents were applied on the epidural region after laminectomy was performed until the identification of dura mater and nerve root. After a follow up period of 12 weeks, rats were sacrificed, and histologic sections were performed proximal and distal to laminectomy zone. Groups were histopathologically compared in terms of chronic inflammation, fibrosis, and vascularization. RESULTS: There was no difference between groups in terms of acute inflammation (P = 0.159). Chronic inflammation was more remarkable in the herbal hemostatic group (P = 0.036), and there was severe fibrosis in absorbable collagen hemostatic, fibrin sealant, and powder hemostatic agent groups (P < 0.001). Vascularity was more obvious in herbal hemostatic; fibrin sealant; absorbable collagen; fibrin sealant containing fibrinogen, factor XIII, and thrombin; hemostatic powder; and oxidized cellulose polymer groups (P < 0.001). CONCLUSIONS: Hemostatic agents can cause notable histopathologic alterations, including inflammation, fibrosis, and vascularity. In this context, flowable hemostats such as gelatin granules and thrombin or gelatin paste seem to provide more promising results in spinal surgery. PMID- 26898494 TI - Prospective Comparison of Microsurgical, Tubular-Based Endoscopic, and Endoscopically Assisted Diskectomies: Clinical Effectiveness and Complications in Railway Workers. AB - OBJECTIVE: Although endoscopic diskectomy is superior to microsurgical diskectomy in terms of incision size, postoperative pain, and cosmetic appeal, the effectiveness and indications for endoscopic versus microsurgical diskectomy remain active discussion topics. Because of the increasing incidence of diskectomies being performed in Russia, further assessment of these techniques is needed. We performed a comparative analysis of 1-year clinical results and complications of microsurgical, tubular-based interlaminar endoscopic, and endoscopically assisted microsurgical diskectomies for patients with herniated lumbar disks. METHODS: The patient cohort included 131 patients who were enrolled in a prospective, randomized controlled study and 617 patients for whom data were gathered retrospectively. The quality of life was assessed using the Oswestry Disability Index (version 2.1a) and pain severity was analyzed using the visual analog scale for pain preoperatively, at discharge, and at 3, 6, and 12 months postoperatively. RESULTS: Microsurgical, tubular-based endoscopic, and endoscopically assisted microsurgical diskectomies were all effective in relieving acute radicular symptoms. Recurrent disk herniation occurred more frequently after tubular-based endoscopic diskectomy than after the other approaches. CONCLUSIONS: Our findings indicate that these 3 surgical techniques are highly effective and have similar clinical results at 1-year follow-up. Although this study points to differences in complications resulting from the 3 techniques, larger prospective studies are needed to more definitively assess possible surgical differences, complications, and outcomes. The endoscopically assisted diskectomy technique allows for minimally invasive surgery and offers enhanced visualization of the anatomy that is hidden from view in microscopic procedures. PMID- 26898495 TI - Neuroendoscopic Trans-Third Ventricular Approach for Surgical Management of Ecchordosis Physaliphora. AB - BACKGROUND: We sought to report the successful surgical management of a case of ecchordosis physaliphora (EP) using a neuro-endoscopic trans-third ventricular approach (ETTVA) and to provide a current review of literature on EP. CASE DESCRIPTION: A 57-year-old man presenting with a 2-year history of diplopia due to right abducens nerve palsy and paresthesia of the left body underwent magnetic resonance imaging, which revealed a retroclival intracisternal lesion. The cystic lesion was considered to be most likely EP according to neuroradiologic features. The patient underwent an endoscopic trans-third ventricular resection. A pediatric endoscope was passed from a precoronal burr hole through the left lateral into the third ventricle. The floor of the third ventricle was opened by a 2-micron laser. This approach permitted us to expose the lesion in the retroclival cistern and follow up with a subtotal removal. Remnants of the capsule, which were firmly adherent to small pontine arteries and the left abducens nerve, were left. Histology confirmed EP. The patient recovered well from surgery, and symptoms regressed at clinical follow-up. CONCLUSION: The endoscopic approach for third ventriculostomy can also be used for the surgical management of retroclival lesions. However, a small pediatric endoscope with an angled view, which can be passed through the floor of the third ventricle without causing harm, is mandatory to explore all important structures in the narrow surgical space. Limitations in this delicate environment are firm adhesions to vessels and nerves because only 1-instrument manipulation is possible and bleeding must be avoided. PMID- 26898496 TI - Google Search Queries About Neurosurgical Topics: Are They a Suitable Guide for Neurosurgeons? AB - OBJECTIVE: Google is the most popular search engine, with about 100 billion searches per month. Google Trends is an integrated tool that allows users to obtain Google's search popularity statistics from the last decade. Our aim was to evaluate whether Google Trends is a useful tool to assess the public's interest in specific neurosurgical topics. METHODS: We evaluated Google Trends statistics for the neurosurgical search topic areas "hydrocephalus," "spinal stenosis," "concussion," "vestibular schwannoma," and "cerebral arteriovenous malformation." We compared these with bibliometric data from PubMed and epidemiologic data from the German Federal Monitoring Agency. In addition, we assessed Google users' search behavior for the search terms "glioblastoma" and "meningioma." RESULTS: Over the last 10 years, there has been an increasing interest in the topic "concussion" from Internet users in general and scientists. "Spinal stenosis," "concussion," and "vestibular schwannoma" are topics that are of special interest in high-income countries (eg, Germany), whereas "hydrocephalus" is a popular topic in low- and middle-income countries. The Google-defined top searches within these topic areas revealed more detail about people's interests (eg, "normal pressure hydrocephalus" or "football concussion" ranked among the most popular search queries within the corresponding topics). There was a similar volume of queries for "glioblastoma" and "meningioma." CONCLUSIONS: Google Trends is a useful source to elicit information about general trends in peoples' health interests and the role of different diseases across the world. The Internet presence of neurosurgical units and surgeons can be guided by online users' interests to achieve high-quality, professional-endorsed patient education. PMID- 26898497 TI - Angioarchitectural Risk Factors for Hemorrhage and Clinical Long-Term Outcome in Pediatric Patients with Cerebral Arteriovenous Malformations. AB - BACKGROUND: Intracranial arteriovenous malformation (AVM) in children is a rare diagnosis. Little is known about factors determining AVM rupture and appropriate treatment strategies to prevent hemorrhage and associated disability. Available data suggest that children are subject to an increased risk for AVM rupture compared with adults. METHODS: In 46 pediatric patients with AVM, demographic factors, clinical presentation, angioarchitectural features, and treatment regimens as well as clinical and radiologic outcomes were retrospectively analyzed. First-line treatment option was microsurgical resection of the disease, with or without preoperative embolization. RESULTS: Twenty-four boys (52.2%) and 22 girls (47.8%) with a mean age on admission of 12.4 years (4-18 years) were included. Mean follow-up was 4 years (median, 1.5; range, 0.1-16.4). Thirty-one children presented with intracerebral hemorrhage (67.4%). Small AVMs (<3 cm) ruptured in 83.3% (n = 25) and were shown to be more prone to hemorrhage than larger ones (P < 0.01). Small AVM size (P < 0.01; odds ratio [OR], 0.12; 95% confidence interval [CI] 0.02-0.59) and exclusive deep venous drainage (P < 0.01; OR, 29.74; 95% CI, 2.45-4445.34) were independent risk factors for hemorrhage in the presented cohort. Good long-term outcome was associated with a high score on the Glasgow Coma Scale on admittance (P < 0.05; OR, 0.148; 95% CI, 0.03-0.73). CONCLUSIONS: Two-thirds of children with AVM are admitted with intracerebral hemorrhage. Microsurgical resection was successful as confirmed by radiologic studies in 95%, and 79.5% of patients presented in a good clinical condition on follow-up (modified Rankin Scale 0 or 1). Microsurgical treatment is recommended if the lesion is accessible and angioarchitectural risk factors favor definitive treatment. PMID- 26898498 TI - Awake Craniotomy: First-Year Experiences and Patient Perception. AB - BACKGROUND: Awake craniotomy for brain lesions in or near eloquent brain regions enables neurosurgeons to assess neurologic functions of patients intraoperatively, reducing the risk of permanent neurologic deficits and increasing the extent of resection. METHODS: A retrospective review was performed of a consecutive series of patients with awake craniotomies in the first year of their introduction to our tertiary non-university-affiliated neurosurgery department. Operation time, complications, and neurologic outcome were assessed, and patient perception of awake craniotomy was surveyed using a mailed questionnaire. RESULTS: There were 24 awake craniotomies performed in 22 patients for low-grade/high-grade gliomas, cavernomas, and metastases (average 2 cases per month). Mean operation time was 205 minutes. Failure of awake craniotomy because of intraoperative seizures with subsequent postictal impaired testing or limited cooperation occurred in 2 patients. Transient neurologic deficits occurred in 29% of patients; 1 patient sustained a permanent neurologic deficit. Of the 18 patients (82%) who returned the questionnaire, only 2 patients recalled significant fear during surgery. CONCLUSIONS: Introducing awake craniotomy to a tertiary non-university-affiliated neurosurgery department is feasible and resulted in reasonable operation times and complication rates and high patient satisfaction. PMID- 26898499 TI - Application of Convection-Enhanced Drug Delivery in the Treatment of Malignant Gliomas. AB - Convection-enhanced delivery (CED) is a promising new method of local drug delivery therapy for a diverse type of antitumor agents. CED offers significant advantages over systemic chemotherapy by bypassing the blood-brain barrier and obtaining adequate drug concentration with limited systemic toxicity. Actually, there is no effective treatment of malignant gliomas (MGs); survival rates remain poor despite decades of clinical trials. Conventional chemotherapy has been found to be minimally effective in the control of MG progression. CED involves the implantation of catheters through which conventional and novel therapeutic formulations can be delivered directly to the tumor using continuous, low positive-pressure bulk flow. On the basis of the preclinical and clinical studies, we demonstrated that CED could produce effective drug delivery to large brain and tumor areas. However, clinical studies to date have not found any substantial improvement in overall survival in the treatment of MG. This overview presents up-to-date clinical results in the treatment of MG by the application of CED. PMID- 26898500 TI - Slow and fast development in two aphidophagous ladybirds on scarce and abundant prey supply. AB - Developmental rates are highly variable, both within and between genotypes and populations. But the rationale for two differential (slow and fast) developmental rates within same cohort under varying prey supply has yet not been explored. For this purpose, we investigated the effect of scarce and abundant prey supply on slow and fast development at 27 degrees C in two aphidophagous ladybirds, Menochilus sexmaculatus (Fabricius) and Propylea dissecta (Mulsant) and its effect on their body mass and reproductive attributes. The ladybirds were provided with scarce and abundant supply of Aphis craccivora Koch under standardized abiotic conditions in the laboratory. A clear bimodal (two peaks, where the first peak represented the fast developing individuals and the second peak slow developing individuals) pattern of distribution for both prey supplies was obtained, which got skewed with change in prey supply. On abundant prey supply, more fast developing individuals (139 M. sexmaculatus and 123 P. dissecta) were found and less (46 M. sexmaculatus and 36 P. dissecta) on scarce prey supply. Slow developing individuals had female biased sex ratio, higher longevity and lower body mass. Fast developing females laid higher number of eggs with higher egg viability. Results of the study are indicative of occurrence and constancy of the slow and fast developing individuals in the egg batch. PMID- 26898501 TI - Details in the catalytic mechanism of mammalian thioredoxin reductase 1 revealed using point mutations and juglone-coupled enzyme activities. AB - The mammalian selenoprotein thioredoxin reductase 1 (TrxR1) is a key enzyme in redox regulation, antioxidant defense, and cellular growth. TrxR1 can catalyze efficient reduction of juglone (5-hydroxy-1,4-naphthoquinone; walnut toxin) in a reaction which, in contrast to reduction of most other substrates of TrxR1, is not dependent upon an intact selenocysteine (Sec, U) residue of the enzyme. Using a number of TrxR1 mutant variants, we here found that a sole Cys residue at the C terminal tail of TrxR1 is required for high-efficiency juglone-coupled NADPH oxidase activity of Sec-deficient enzyme, occurring with mixed one- and two electron reactions producing superoxide. The activity also utilizes the FAD and the N-terminal redox active disulfide/dithiol motif of TrxR1. If a sole Cys residue at the C-terminal tail of TrxR1, in the absence of Sec, was moved further towards the C-terminal end of the protein compared to its natural position at residue 497, juglone reduction was, surprisingly, further increased. Ala substitutions of Trp407, Asn418 and Asn419 in a previously described "guiding bar", thought to mediate interactions of the C-terminal tail of TrxR1 with the FAD/dithiol site at the N-terminal domain of the other subunit in the dimeric enzyme, lowered turnover with juglone about 4.5-fold. Four residues of Sec deficient TrxR1 were found to be easily arylated by juglone, including the Cys residue at position 497. Based upon our observations we suggest a model for involvement of the juglone-arylated C-terminal motif of TrxR1 to explain its high activity with juglone. This study thus provides novel insights into the catalytic mechanisms of TrxR1. One-electron juglone reduction by TrxR1 producing superoxide should furthermore contribute to the well-known prooxidant cytotoxicity of juglone. PMID- 26898502 TI - Cellular targets of the myeloperoxidase-derived oxidant hypothiocyanous acid (HOSCN) and its role in the inhibition of glycolysis in macrophages. AB - Myeloperoxidase (MPO) released at sites of inflammation catalyzes the formation of the oxidants hypochlorous acid (HOCl) and hypothiocyanous acid (HOSCN) from H2O2 and halide and pseudo-halide ions. HOCl, a major oxidant produced under physiological conditions reacts rapidly with many biological molecules, and is strongly linked with tissue damage during inflammatory disease. The role of HOSCN in disease is less clear, though it can initiate cellular damage by pathways involving the selective oxidation of thiol-containing proteins. Utilizing a thiol specific proteomic approach, we explored the cellular targets of HOSCN in macrophages (J774A.1). We report that multiple thiol-containing proteins involved in metabolism and glycolysis; fructose bisphosphate aldolase, triosephosphate isomerase, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and creatine kinase, together with a number of chaperone, antioxidant and structural proteins, were modified in a reversible manner in macrophages treated with HOSCN. The modification of the metabolic enzymes was associated with a decrease in basal glycolysis, glycolytic reserve, glycolytic capacity and lactate release, which was only partly reversible on further incubation in the absence of HOSCN. Inhibition of glycolysis preceded cell death and was seen in cells exposed to low concentrations (<=25uM) of HOSCN. The ability of HOSCN to inhibit glycolysis and perturb energy production is likely to contribute to the cell death seen in macrophages on further incubation after the initial treatment period, which may be relevant for the propagation of inflammatory disease in smokers, who have elevated plasma levels of the HOSCN precursor, thiocyanate. PMID- 26898504 TI - Interaction of singlet oxygen with bovine serum albumin and the role of the protein nano-compartmentalization. AB - Singlet molecular oxygen ((1)O2) contributes to protein damage triggering biophysical and biochemical changes that can be related with aging and oxidative stress. Serum albumins, such as bovine serum albumin (BSA), are abundant proteins in blood plasma with different biological functions. This paper presents a kinetic and spectroscopic study of the (1)O2-mediated oxidation of BSA using the tris(2,2'-bipyridine)ruthenium(II) cation [Ru(bpy)3](2+) as sensitizer. BSA quenches efficiently (1)O2 with a total (chemical+physical interaction) rate constant kt(BSA)=7.3(+/-0.4)*10(8)M(-1)s(-1), where the chemical pathway represented 37% of the interaction. This efficient quenching by BSA indicates the participation of several reactive residues. MALDI-TOF MS analysis of intact BSA confirmed that after oxidation by (1)O2, the mass protein increased the equivalent of 13 oxygen atoms. Time-resolved emission spectra analysis of BSA established that Trp residues were oxidized to N'-formylkynurenine, being the solvent-accessible W134 preferentially oxidized by (1)O2 as compared with the buried W213. MS confirmed oxidation of at least two Tyr residues to form dihydroxyphenylalanine, with a global reactivity towards (1)O2 six-times lower than for Trp residues. Despite the lack of MS evidences, kinetic and chemical analysis also suggested that residues other than Trp and Tyr, e.g. Met, must react with (1)O2. Modeling of the 3D-structure of BSA indicated that the oxidation pattern involves a random distribution of (1)O2 into BSA; allowing also the interaction of (1)O2 with buried residues by its diffusion from the bulk solvent through interconnected internal hydrophilic and hydrophobic grooves. PMID- 26898506 TI - Biomechanical characteristics of self-ligating brackets in a vertically displaced canine model: a finite element analysis. AB - OBJECTIVES: The objective of this study was to compare the biomechanical characteristics between two types of self-ligating brackets and conventional metal brackets using finite element analysis of a vertically displaced canine model focusing on the desired force on the canine and undesirable forces on adjacent teeth. MATERIALS AND METHODS: Three-dimensional finite element models of the maxillary dentition with 1-mm, 2-mm, and 3-mm vertically displaced canines were constructed. Two different self-ligating brackets (In-Ovation C and Smart clip) and a conventional metal bracket (Micro-arch) were modeled. After a 0.016 inch NiTi (0.40 mm, round) wire was engaged, the displacement of each tooth was calculated using x-, y-, and z-coordinates, and the tensile and compressive stresses were calculated. RESULTS: The extrusion and maximal tensile stress of the canine differed little between the three brackets, but the intrusion and minimal compressive stress values of the adjacent teeth differed considerably and were highest in the Smart clip and least in the In-Ovation C. The extrusion and maximal tensile stress of the canine in the 3-mm displacement model was less than that in the 2-mm displacement model, and the intrusion and minimal compressive stress of the adjacent teeth increased with the degree of displacement. CONCLUSIONS: Self-ligating brackets were not superior to conventional brackets in leveling a vertically displaced canine. A continuous arch wire may not be recommended for leveling of severely displaced canines whether using self ligating or conventional brackets. PMID- 26898505 TI - Differentially expressed lncRNAs and mRNAs identified by microarray analysis in GBS patients vs healthy controls. AB - The aim of our present study was to determine whether message RNAs (mRNAs) and long noncoding RNAs (lncRNAs) are expressed differentially in patients with Guillain-Barre syndrome (GBS) compared with healthy controls. The mRNA and lncRNA profiles of GBS patients and healthy controls were generated by using microarray analysis. From microarray analysis, we listed 310 mRNAs and 114 lncRNAs with the mRMR software classed into two sample groups, GBS patients and healthy controls. KEGG mapping demonstrated that the top seven signal pathways may play important roles in GBS development. Several GO terms, such as cytosol, cellular macromolecular complex assembly, cell cycle, ligase activity, protein catabolic process, etc., were enriched in gene lists, suggesting a potential correlation with GBS development. Co-expression network analysis indicated that 113 lncRNAs and 303 mRNAs were included in the co-expression network. Our present study showed that these differentially expressed mRNAs and lncRNAs may play important roles in GBS development, which provides basic information for defining the mechanism(s) that promote GBS. PMID- 26898503 TI - Ascorbic acid repletion: A possible therapy for diabetic macular edema? AB - Macular edema poses a significant risk for visual loss in persons with diabetic retinopathy. It occurs when plasma constituents and fluid leak out of damaged retinal microvasculature in the area of the macula, causing loss of central vision. Apoptotic loss of pericytes surrounding capillaries is perhaps the earliest feature of diabetic vascular damage in the macula, which is also associated with dysfunction of the endothelium and loss of the otherwise very tight endothelial permeability barrier. Increased oxidative stress is a key feature of damage to both cell types, mediated by excess superoxide from glucose induced increases in mitochondrial metabolism, as well as by activation of the receptor for advanced glycation end products (RAGE). The latter in turn activates multiple pathways, some of which lead to increased oxidative stress, such as those involving NF-KB, NADPH oxidase, and endothelial nitric oxide synthase. Such cellular oxidative stress is associated with low cellular and plasma ascorbic acid levels in many subjects with diabetes in poor glycemic control. Whether repletion of low ascorbate in retinal endothelium and pericytes might help to prevent diabetic macular edema is unknown. However, cell culture studies show that the vitamin prevents high-glucose and RAGE-induced apoptosis in both cell types, that it preserves nitric oxide generated by endothelial cells, and that it tightens the leaky endothelial permeability barrier. Although these findings need to be confirmed in pre-clinical animal studies, it is worth considering clinical trials to determine whether adequate ascorbate repletion is possible and whether it might help to delay or even reverse early diabetic macular edema. PMID- 26898507 TI - Perspectives for vanadium in health issues. AB - Vanadium is omnipresent in trace amounts in the environment, in food and also in the human body, where it might serve as a regulator for phosphate-dependent proteins. Potential vanadium-based formulations--inorganic and coordination compounds with organic ligands--commonly underlie speciation in the body, that is, they are converted to vanadate(V), oxidovanadium(IV) and to complexes with the body's own ligand systems. Vanadium compounds have been shown to be potentially effective against diabetes Type 2, malign tumors including cancer, endemic tropical diseases (such as trypanosomiasis, leishmaniasis and amoebiasis), bacterial infections (tuberculosis and pneumonia) and HIV infections. Furthermore, vanadium drugs can be operative in cardio- and neuro protection. So far, vanadium compounds have not yet been approved as pharmaceuticals for clinical use. PMID- 26898508 TI - Assessment of the quality of very high-energy electron radiotherapy planning. AB - BACKGROUND AND PURPOSE: To assess the quality of very-high energy electron (VHEE) scanning pencil beam radiation therapy in relation to state-of-the-art volumetric modulated arc therapy (VMAT) and to determine the extent of its application. MATERIAL AND METHODS: We planned five clinical cases with VHEE scanning pencil beams of 100 and 120MeV, equally distributed in a coplanar arrangement around the patient. The clinical cases included acoustic neuroma, and liver, lung, esophagus, and anal cancer cases. We performed Monte Carlo (MC) dose calculations and we optimized the dose in a research version of RayStation. VHEE plan performance was compared against clinically delivered VMAT. RESULTS: With equal target coverage, mean doses to organs at risk (OARs) were on average 22% lower for the VHEE plans compared to the VMAT plans. Dose conformity was equal or superior compared to the VMAT plans and integral dose to the body was in average 14% (9-22%) lower for the VHEE plans. CONCLUSIONS: The dosimetric advantages of VHEE as demonstrated for a variety of clinical cases, combined with the theoretical ultra fast treatment delivery, afford VHEE scanning pencil beam radiotherapy a suitable and potentially superior alternative for cancer radiotherapy. PMID- 26898510 TI - Research that Guides Practice: Outcome Research in Swedish PhD Theses Across Seven Disciplines 1997-2012. AB - The core of evidence-based practice (EBP) as advocated for within the practice arms of the health and social sciences is to promote the routine incorporation of the best available research evidence into practice efforts. This requires discipline-specific education that is not only grounded in professional practice but also prepares would-be scientists in the application of the sophisticated techniques that characterize today's high research standards. Doctoral-level education is an important primer for future scientific endeavors across disciplines. This study examined 2334 theses published across Sweden in public health, criminology, nursing, psychiatry, psychology, social work, and sociology during the period 1997-2012. Of the theses reviewed, 13% aimed to investigate the effects of interventions. The highest percentage of effectiveness studies was found in nursing, public health, and psychology. The percentage of outcome research increased during the period. Controlled studies (with comparison group and pre- and post-test) occurred primarily within public health, nursing, psychiatry, and psychology. Of the 296 theses that included an intervention effectiveness study, 131 (44%), or 5.6% of all theses reviewed, met all four assessment criteria for quality. PhD education across seven disciplines in Sweden may be producing a professional core of scientists that is ill prepared to produce the type of research that is necessary to inform practice of the effects of its interventions as exposure to the rigors of quality effectiveness research is all but non-existent. This has implications for the advancement of an evidence based practice and intervention science more broadly. PMID- 26898509 TI - Understanding Associations Between Neighborhood Socioeconomic Status and Negative Consequences of Drinking: a Moderated Mediation Analysis. AB - We explored how neighborhood socioeconomic status (SES) is related to negative consequences of drinking to explain why racial/ethnic minority group members are more at risk than Whites for adverse alcohol outcomes. We tested direct and indirect effects of neighborhood SES on alcohol problems and examined differences by gender and race. We used data from the 2000 and 2005 National Alcohol Surveys (N = 7912 drinkers aged 18 and older; 49 % female) linked with data from the 2000 Decennial Census in multivariate path models adjusting for individual demographics. In the full sample, neighborhood disadvantage had a significant direct path to increased negative consequences, with no indirect paths through depression, positive affect or pro-drinking attitudes. Neighborhood affluence had significant indirect paths to increased negative consequences through greater pro drinking attitudes and increased heavy drinking. Subgroup analyses showed the indirect path from affluence to consequences held for White men, with no effects of neighborhood disadvantage. For racial/ethnic minority men, significant indirect paths emerged from both neighborhood disadvantage and affluence to increased consequences through greater pro-drinking attitudes and more heavy drinking. For minority women, there was an indirect effect of neighborhood affluence through reduced depression to fewer drinking consequences. There were limited neighborhood effects on alcohol outcomes for White women. Interventions targeting pro-drinking attitudes in both affluent and disadvantaged areas may help reduce alcohol-related problems among men. Initiatives to improve neighborhood conditions could enhance mental health of minority women and reduce alcohol-related health disparities. PMID- 26898511 TI - Possibilities for preservation of coarse particles in pelleting process to improve feed quality characteristics. AB - Poultry diets are mainly used in pelleted form because pellets have many advantages compared to mash feed. On the other hand, pelleting causes reduction of feed particle size. The aim of this research was to investigate the possibility of increasing the content of coarse particles in pellets, and, at the same time, to produce pellets with satisfactory quality. In this research, the three grinding treatments of corn were applied using hammer mill with three sieve openings diameter: 3 mm (HM-3), 6 mm (HM-6) and 9 mm (HM-9). These grinding treatments were combined in pelleting process with three gaps between rollers and the die of pellet press (roller-die gap, RDG) (0.30, 1.15 and 2.00 mm) and three moisture contents of the pelleted material (14.5, 16.0 and 17.5%). The increased coarseness of grinding by the hammer mill resulted in the increased amount of coarse particles in pellets, especially when the smallest RDG was applied (0.30 mm), but pellet quality was greatly reduced. Increasing of RDG improved the quality of pellets produced from coarsely ground corn, but reduced the content of coarse particles in pellets and increased specific energy consumption of the pellet press. Increasing the moisture content of material to be pelleted (MC) significantly reduced energy consumption of the pellet press, but there was no significant influence of MC on particle size after pelleting and on the pellet quality. The optimal values of the pelleting process parameters were determined using desirability function method. The results of optimization process showed that to achieve the highest possible quantity of coarse particles in the pellets, and to produce pellets of satisfactory quality, with the lowest possible energy consumption of the pellet press, the coarsest grinding on hammer mill (HM-9), the largest RDG (2 mm) and the highest MC (17.5%) should be applied. PMID- 26898512 TI - Current Guidelines in the Management of Upper Gastrointestinal Subepithelial Tumors. AB - Subepithelial tumors are frequently found in asymptomatic patients in Japan and Korea where cancer screening tests routinely include endoscopy. Most lesions are asymptomatic and clinically insignificant. However, carcinoid tumors, lymphomas, glomus tumor and gastrointestinal stromal tumors (GISTs) are malignant or have the potential to become malignant. Inflammation due to parasitic infestation by Anisakis and poorly differentiated adenocarcinomas in the stomach rarely present as subepithelial lesions. In contrast to the frequency of gastric GIST in the gastrointestinal system, they are uncommon in the duodenum and very rare in the esophagus. The prognosis of patients with GISTs in the stomach is relatively good compared with GISTs in other organs. Along with the location of the tumor, its size and mitotic count are major factors that determine the malignant potential of GIST. Small (<2 cm) asymptomatic GISTs usually have benign clinical course. GIST is the most common subepithelial tumor to occur in the stomach. Although various methods are employed to diagnose GISTs, the risk of GIST metastasis cannot be accurately predicted before lesions are completely resected. Recently, new endoscopic diagnostic methods and treatment techniques have been developed that allow the diagnosis and resection of lesions located in the muscularis propria, without any complications. These endoscopic methods have different indications depending on regions where they are performed. PMID- 26898513 TI - Job Stress and Job Satisfaction among Health-Care Workers of Endoscopy Units in Korea. AB - BACKGROUND/AIMS: The management of job-related stress among health-care workers is critical for the improvement of healthcare services; however, there is no existing research on endoscopy unit workers as a team. Korea has a unique health care system for endoscopy unit workers. In this study, we aimed to estimate job stress and job satisfaction among health-care providers in endoscopy units in Korea. METHODS: We performed a cross-sectional survey of health-care providers in the endoscopy units of three university-affiliated hospitals in Korea. We analyzed the job stress levels by using the Korean occupational stress scale, contributing factors, and job satisfaction. RESULTS: Fifty-nine workers completed the self-administered questionnaires. The job stress scores for the endoscopy unit workers (46.39+/-7.81) were relatively lower compared to those of the national sample of Korean workers (51.23+/-8.83). Job stress differed across job positions, with nurses showing significantly higher levels of stress (48.92+/ 7.97) compared to doctors (42.59+/-6.37). Job stress and job satisfaction were negatively correlated with each other (R (2) =0.340, p<0.001). CONCLUSIONS: An endoscopy unit is composed of a heterogeneous group of health-care professionals (i.e., nurses, fellows, and professors), and job stress and job satisfaction significantly differ according to job positions. Job demand, insufficient job control, and job insecurity are the most important stressors in the endoscopy unit. PMID- 26898514 TI - Two Cases of Cerebral Air Embolism That Occurred during Esophageal Ballooning and Endoscopic Retrograde Cholangiopancreatography. AB - Cerebral air embolism is an extremely rare complication of endoscopic procedure and often life threatening. We present two cases of cerebral infarction due to air embolization caused by an endoscopic intervention. The first case occurred during esophageal balloon dilatation for the treatment of a stricture of an anastomosis site in a 59-year-old man and the second case occurred during endoscopic papillary balloon dilatation in a 69-year-old man who had distal common bile duct stones. After the procedure, cardiopulmonary instability and altered mental status were observed in both patients, and cerebral air embolism was diagnosed in both cases. Hyperbaric oxygen therapy was started in the first case, and high FiO2 therapy was applied in the second case. Although this complication is rare, patient outcomes can be improved if physicians are aware of this potential complication, and immediately begin proper management. PMID- 26898515 TI - Angioimmunoblastic T-cell lymphoma mimicking dermatomyositis. PMID- 26898516 TI - Modeling healthcare data using multiple-channel latent Dirichlet allocation. AB - Information and communications technologies have enabled healthcare institutions to accumulate large amounts of healthcare data that include diagnoses, medications, and additional contextual information such as patient demographics. To gain a better understanding of big healthcare data and to develop better data driven clinical decision support systems, we propose a novel multiple-channel latent Dirichlet allocation (MCLDA) approach for modeling diagnoses, medications, and contextual information in healthcare data. The proposed MCLDA model assumes that a latent health status group structure is responsible for the observed co occurrences among diagnoses, medications, and contextual information. Using a real-world research testbed that includes one million healthcare insurance claim records, we investigate the utility of MCLDA. Our empirical evaluation results suggest that MCLDA is capable of capturing the comorbidity structures and linking them with the distribution of medications. Moreover, MCLDA is able to identify the pairing between diagnoses and medications in a record based on the assigned latent groups. MCLDA can also be employed to predict missing medications or diagnoses given partial records. Our evaluation results also show that, in most cases, MCLDA outperforms alternative methods such as logistic regressions and the k-nearest-neighbor (KNN) model for two prediction tasks, i.e., medication and diagnosis prediction. Thus, MCLDA represents a promising approach to modeling healthcare data for clinical decision support. PMID- 26898517 TI - Encapsulated Laccases for the Room-Temperature Oxidation of Aromatics: Towards Synthetic Low-Molecular-Weight Lignins. AB - A new approach for the encapsulation of laccases with enhanced activity and stability by biomimetic silica mineralisation is reported. A range of lignin model compounds, which includes syringol, syringyl acid, 4-vinylphenol, gallic acid, vanillic acid and guaiacol, was oxidised to lignin-type polymers by the silica-immobilised laccase systems at room temperature. The oxidation rate of the immobilised systems was lower than that of the free enzyme counterparts, but interesting products were observed with the new bio-catalytic materials, which showed reusability and good stability. PMID- 26898518 TI - The SECONDI MAPZ((c)) system: a practical guide and proof of concept. AB - The SECONDI MAPZ((c)) system is a new, simple, and logical classification of oncological defects of the midface that combines regional anatomy, 3-dimensional visualisation, and the hierarchy of functional priorities. In this paper, we provide clinical and radiographic examples of defects of varying complexity to illustrate the application of the system, to highlight its versatility, and to give practical clinical and radiological guidance on its use. We hope that its introduction will result in better communication of information, and the collection of more uniform data with which to compare outcomes, and ultimately will facilitate evidence-based practice in head and neck oncology. PMID- 26898519 TI - Accuracy of mandibular reconstruction by three-dimensional guided vascularised fibular free flap after segmental mandibulectomy. AB - Mandibular reconstruction with a fibular free flap has become standard in specialised centres for head and neck reconstruction, particularly for defects with more than one osteotomy that are challenging even for experienced surgeons. Virtual surgical planning is a potential tool to facilitate harvesting of the fibula and the osteostomy. The purpose of this study was to compare the two methods of mandibular reconstruction - conventionally planned (conventional group) and "virtually" planned (virtual group) - with regard to accuracy, bony consolidation, complications, and operating time. Fifty patients who required mandibular reconstruction after segmental mandibulectomy were evaluated retrospectively, 24 virtually planned and 26 conventionally planned. The overall survival of flaps was 92% (46/50). The bony consolidation rate in the virtual group was significantly better than that in the conventional group (p=0.002). The difference between the angle of the mandible before and after was highly significant with a median of 11.5 degrees (range 2 degrees -75 degrees ) in the conventional group and 4.5 degrees (range 0-18 degrees ) in the virtual group (p=0.0001). Operations were mean (SD) of 34 (21.2) minutes shorter in virtually planned cases (p=0.12). The overall morbidity did not differ significantly between the groups. The use of virtual surgical planning in mandibular reconstruction by fibular free flap is beneficial for optimising accuracy, consolidation of bony segments, and operating time, while increasing the predictability of results for the surgeon. However, additional costs have to be carefully weighed against the benefits. PMID- 26898520 TI - The role of the K-channel and the active-site tyrosine in the catalytic mechanism of cytochrome c oxidase. AB - The active site of cytochrome c oxidase (CcO) comprises an oxygen-binding heme, a nearby copper ion (CuB), and a tyrosine residue that is covalently linked to one of the histidine ligands of CuB. Two proton-conducting pathways are observed in CcO, namely the D- and the K-channels, which are used to transfer protons either to the active site of oxygen reduction (substrate protons) or for pumping. Proton transfer through the D-channel is very fast, and its role in efficient transfer of both substrate and pumped protons is well established. However, it has not been fully clear why a separate K-channel is required, apparently for the supply of substrate protons only. In this work, we have analysed the available experimental and computational data, based on which we provide new perspectives on the role of the K-channel. Our analysis suggests that proton transfer in the K channel may be gated by the protonation state of the active-site tyrosine (Tyr244) and that the neutral radical form of this residue has a more general role in the CcO mechanism than thought previously. This article is part of a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016', edited by Prof. Paolo Bernardi. PMID- 26898521 TI - Unexpected uterine malignancy following laparoscopic hysterectomy with morcellation. PMID- 26898522 TI - Fear of Public Speaking: Perception of College Students and Correlates. AB - OBJECTIVES: The aims of the study were to determine the prevalence of fear of public speaking among college students and to assess its association with sociodemographic variables and those related to the voice and oral communication. METHODS: A cross-sectional descriptive and analytic study was conducted with 1135 undergraduates aged 17-58 years. The assessment instruments were (1) a questionnaire addressing the variables sex, age, field of undergraduate study, voice, and frequency of exposure to public speaking, and (2) the Self-statements During Public Speaking Scale (SSPS), which includes variables implicated in specific domains of public speaking. A descriptive analysis was performed of the variables as well as uni- and multivariate logistic regressions to examine their association with fear of public speaking. The level of significance was set at 5%. RESULTS: In all, 63.9% of the college students reported fear of public speaking. As many as 89.3% of the students would like their undergraduate program to include classes to improve public speaking. Being female, having infrequent participation as speakers in groups, and perceiving their voice as high-pitched or too soft increase the odds of exhibiting fear of public speaking compared with students without those features. CONCLUSION: A great number of undergraduates report fear of public speaking. This fear is more prevalent among women, students who participate in few activities involving speaking to groups of people, and those who have a self-perception of their voice as high-pitched or too soft. PMID- 26898523 TI - Noninvasive Detection of Cardiac Allograft Vasculopathy by Stress Exercise Echocardiographic Assessment of Myocardial Deformation. AB - BACKGROUND: The aim of this study was to evaluate the value of noninvasive assessment of cardiac allograft vasculopathy (CAV) in heart-transplanted patients by exercise stress myocardial deformation and coronary flow reserve (CFR) assessment. METHODS: Fifty-eight heart-transplanted patients underwent semisupine exercise echocardiography with assessment of left ventricular (LV) longitudinal myocardial deformation. CAV was assessed by coronary angiography and noninvasive CFR by (15)O-H2O positron emission tomographic imaging and Doppler echocardiography. Patients were divided into three groups on the basis of angiographic CAV: no CAV (n = 21), mild CAV (n = 19), and severe CAV (n = 18). RESULTS: Patients with severe CAV had significantly lower LV global longitudinal strain (GLS) at rest (no CAV, -16 +/- 2%; mild CAV, -15 +/- 2%; severe CAV, -12 +/- 4%; P < .001), failed to increase LV GLS during exercise (no CAV, -5.7 +/- 2.0%; mild CAV, -3.3 +/- 2.9%; severe CAV, -0.2 +/- 2.8%; P < .0001), and had significantly lower echocardiographic coronary flow velocity reserve (CFVR) (no CAV, 3.2 +/- 0.4; mild CAV, 2.7 +/- 0.7; severe CAV, 1.8 +/- 0.5; P < .0001) and PET CFR (no CAV, 3.4 +/- 0.9; mild CAV, 3.1 +/- 0.9; severe CAV, 1.9 +/- 0.8; P < .0001). Furthermore, patients with mild CAV had significantly lower exercise LV GLS and echocardiographic CFVR than patients with no CAV. Exercise LV GLS, echocardiographic CFVR, and PET CFR were significantly correlated with the presence of severe CAV in a logistic regression model (LV GLS odds ratio, 0.71; 95% CI, 0.60-0.84; P < .0001; echocardiographic CFVR odds ratio: 0.06; 95% CI, 0.01-0.23; PET CFR odds ratio, 0.17; 95% CI, 0.07-0.46). This relation remained significant after adjustment for symptoms and time since transplantation. CONCLUSIONS: Noninvasive assessment of LV longitudinal myocardial deformation during exercise is feasible and strongly associated with the presence and degree of CAV. Exercise stress myocardial deformation analysis, echocardiographic CFVR, or PET CFR may serve as a noninvasive model for the detection of CAV. PMID- 26898525 TI - A Resident Perspective on Adding Value as Radiologists. AB - During the annual 46th annual American Alliance of Academic Chief Residents in Radiology (A(3)CR(2)) meeting in New Orleans, chief residents discussed the role of residents within American College of Radiology 3.0 campaign. Our discussion was directed toward the evolving role of fourth-year radiology residents and how we might improve their training to better prepare them to add value as both leaders and radiologists. The ideas resulting from our Problem Solving session were divided into three categories: clinical presence in the wards and subspecialty clinics; visibility to clinicians and patients; and the education of medical students, residents, and advanced practice clinicians to aid in realizing the long-term goals of Imaging 3.0. PMID- 26898526 TI - Most Common Publication Types in Radiology Journals:: What is the Level of Evidence? AB - RATIONALE AND OBJECTIVES: This study aimed to assess the most common publication types in radiology journals, as well as temporal trends and association with citation frequency. MATERIALS AND METHODS: PubMed was searched to extract all published articles having the following "Publication Type" indices: "validation studies," "meta-analysis," "clinical trial," "comparative study," "evaluation study," "guideline," "multicenter study," "randomized study," "review," "editorial," "case report," and "technical report." The percentage of articles within each category published within clinical radiology journals was computed. Normalized percentages for each category were also computed on an annual basis. Citation counts within a 2-year window following publication were obtained using Web of Science. Overall trends were assessed. RESULTS: Publication types with the highest fraction in radiology journals were technical reports, evaluation studies, and case reports (4.8% to 5.8%). Publication types with the lowest fraction in radiology journals were randomized trials, multicenter studies, and meta-analyses (0.8% to 1.5%). Case reports showed a significant decrease since 1999, with accelerating decline since 2007 (P = 0.002). Publication types with highest citation counts were meta-analyses, guidelines, and multicenter studies (8.1 +/- 10.7 to 12.9 +/- 5.1). Publication types with lowest citation counts were case reports, editorials, and technical reports (1.4 +/- 2.4 to 2.9 +/- 4.3). The representation in radiology journals and citation frequency of the publication types showed weak inverse correlation (r = -0.372). CONCLUSIONS: Radiology journals have historically had relatively greater representation of less frequently cited publication types. Various strategies, including methodological training, multidisciplinary collaboration, national support networks, as well as encouragement of higher level of evidence by funding agencies and radiology journals themselves, are warranted to improve the impact of radiological research. PMID- 26898524 TI - Making sense of the sensory regulation of hunger neurons. AB - AgRP and POMC neurons are two key cell types that regulate feeding in response to hormones and nutrients. Recently, it was discovered that these neurons are also rapidly modulated by the mere sight and smell of food. This rapid sensory regulation "resets" the activity of AgRP and POMC neurons before a single bite of food has been consumed. This surprising and counterintuitive discovery challenges longstanding assumptions about the function and regulation of these cells. Here we review these recent findings and discuss their implications for our understanding of feeding behavior. We propose several alternative hypotheses for how these new observations might be integrated into a revised model of the feeding circuit, and also highlight some of the key questions that remain to be answered. PMID- 26898527 TI - Statistical Issues in Testing Conformance with the Quantitative Imaging Biomarker Alliance (QIBA) Profile Claims. AB - A major initiative of the Quantitative Imaging Biomarker Alliance is to develop standards-based documents called "Profiles," which describe one or more technical performance claims for a given imaging modality. The term "actor" denotes any entity (device, software, or person) whose performance must meet certain specifications for the claim to be met. The objective of this paper is to present the statistical issues in testing actors' conformance with the specifications. In particular, we present the general rationale and interpretation of the claims, the minimum requirements for testing whether an actor achieves the performance requirements, the study designs used for testing conformity, and the statistical analysis plan. We use three examples to illustrate the process: apparent diffusion coefficient in solid tumors measured by MRI, change in Perc 15 as a biomarker for the progression of emphysema, and percent change in solid tumor volume by computed tomography as a biomarker for lung cancer progression. PMID- 26898528 TI - Evaluation of the impact on food safety of a Lactobacillus coryniformis strain from pickled vegetables with degradation activity against nitrite and other undesirable compounds. AB - Four strains of lactic acid bacteria showing antimicrobial activity against some food-spoilage microorganisms or pathogens, including both Gram-negative and positive strains, were isolated from naturally fermented pickled vegetables and a traditional cheese product. Among these isolates, Lactobacillus coryniformis strain BBE-H3, characterised previously to be a non-biogenic amine producer, showed a high level of activity in degrading sodium nitrite and exhibited the ability to eliminate ethyl carbamate and one of its precursors, urea. The antimicrobial substance produced by L. coryniformis BBE-H3 was found to be active at an acidic pH range of 4.0-4.5. The antimicrobial activity of this strain decreased differentially after treatment with proteolytic enzymes (pepsin, papain, trypsin and proteinase K), implying this growth inhibitory compound is either a protein or a polypeptide. The results of this study show the suitability of L. coryniformis BBE-H3 as a starter in food manufacturing processes, and demonstrate its potential role in eliminating food origin carcinogens such as sodium nitrite and ethyl carbamate. PMID- 26898530 TI - Using functional genomics to decipher the complexity of microbial pathogenicity. AB - From the first identification of bacteria as a causative agent of disease, researchers have been developing methods and techniques to understand their pathogenic processes. For decades, this work has been limited to looking at a small number of genetically manipulatable isolates in in vitro assays or animal models of infection. Despite these limitations such work has facilitated the development of successful therapeutic strategies, most notably vaccines that target specific virulence-related features. There are however many antimicrobial resistant pathogens for which vaccination strategies have not worked, as we simply do not know enough about how they cause disease. We are however at the dawn of a new era in the study of microbial pathogenicity, where large collections of bacteria isolated directly from human infections can be sequenced and assayed to identify the bacterial features that affect disease severity in humans. Here, we describe our attempt to perform such a study focussed on the major human pathogen Staphylococcus aureus, which demonstrates the step changes such approaches can make to understanding microbial pathogenicity. PMID- 26898531 TI - Anthropogenic plutonium-244 in the environment: Insights into plutonium's longest lived isotope. AB - Owing to the rich history of heavy element production in the unique high flux reactors that operated at the Savannah River Site, USA (SRS) decades ago, trace quantities of plutonium with highly unique isotopic characteristics still persist today in the SRS terrestrial environment. Development of an effective sampling, processing, and analysis strategy enables detailed monitoring of the SRS environment, revealing plutonium isotopic compositions, e.g., (244)Pu, that reflect the unique legacy of plutonium production at SRS. This work describes the first long-term investigation of anthropogenic (244)Pu occurrence in the environment. Environmental samples, consisting of collected foot borne debris, were taken at SRS over an eleven year period, from 2003 to 2014. Separation and purification of trace plutonium was carried out followed by three stage thermal ionization mass spectrometry (3STIMS) measurements for plutonium isotopic content and isotopic ratios. Significant (244)Pu was measured in all of the years sampled with the highest amount observed in 2003. The (244)Pu content, in femtograms (fg = 10(-15) g) per gram, ranged from 0.31 fg/g to 44 fg/g in years 2006 and 2003 respectively. In all years, the (244)Pu/(239)Pu atom ratios were significantly higher than global fallout, ranging from 0.003 to 0.698 in years 2014 and 2003 respectively. PMID- 26898529 TI - Rapid and continuous activity-dependent plasticity of olfactory sensory input. AB - Incorporation of new neurons enables plasticity and repair of circuits in the adult brain. Adult neurogenesis is a key feature of the mammalian olfactory system, with new olfactory sensory neurons (OSNs) wiring into highly organized olfactory bulb (OB) circuits throughout life. However, neither when new postnatally generated OSNs first form synapses nor whether OSNs retain the capacity for synaptogenesis once mature, is known. Therefore, how integration of adult-born OSNs may contribute to lifelong OB plasticity is unclear. Here, we use a combination of electron microscopy, optogenetic activation and in vivo time lapse imaging to show that newly generated OSNs form highly dynamic synapses and are capable of eliciting robust stimulus-locked firing of neurons in the mouse OB. Furthermore, we demonstrate that mature OSN axons undergo continuous activity dependent synaptic remodelling that persists into adulthood. OSN synaptogenesis, therefore, provides a sustained potential for OB plasticity and repair that is much faster than OSN replacement alone. PMID- 26898532 TI - Beyond ketonization: selective conversion of carboxylic acids to olefins over balanced Lewis acid-base pairs. AB - We report the direct conversion of mixed carboxylic acids to C-C olefins with up to 60 mol% carbon yield through cascade (cross) ketonization, (cross) aldolization and self-deoxygenation reactions. Co-feeding hydrogen provides an additional ketone hydrogenation/dehydration pathway to a wider range of olefins. PMID- 26898534 TI - Response to the Letter. PMID- 26898533 TI - The dynamics of protein body formation in developing wheat grain. AB - Wheat is a major source of protein in the diets of humans and livestock but we know little about the mechanisms that determine the patterns of protein synthesis in the developing endosperm. We have used a combination of enrichment with (15) N glutamine and NanoSIMS imaging to establish that the substrate required for protein synthesis is transported radially from its point of entrance in the endosperm cavity across the starchy endosperm tissues, before becoming concentrated in the cells immediately below the aleurone layer. This transport occurs continuously during grain development but may be slower in the later stages. Although older starchy endosperm cells tend to contain larger protein deposits formed by the fusion of small protein bodies, small highly enriched protein bodies may also be present in the same cells. This shows a continuous process of protein body initiation, in both older and younger starchy endosperm cells and in all regions of the tissue. Immunolabeling with specific antibodies shows that the patterns of enrichment are not related to the contents of gluten proteins in the protein bodies. In addition to providing new information on the dynamics of protein deposition, the study demonstrates the wider utility of NanoSIMS and isotope labelling for studying complex developmental processes in plant tissues. PMID- 26898535 TI - Activation of carbon dioxide by a terminal uranium-nitrogen bond in the gas phase: a demonstration of the principle of microscopic reversibility. AB - Activation of CO2 is demonstrated by its spontaneous dissociative reaction with the gas-phase anion complex NUOCl2(-), which can be considered as NUO(+) coordinated by two chloride anion ligands. This reaction was previously predicted by density functional theory to occur exothermically, without barriers above the reactant energy. The present results demonstrate the validity of the prediction of microscopic reversibility, and provide a rare case of spontaneous dissociative addition of CO2 to a gas-phase complex. The activation of CO2 by NUOCl2(-) proceeds by conversion of a U[triple bond, length as m-dash]N bond to a U[double bond, length as m-dash]O bond and creation of an isocyanate ligand to yield the complex UO2(NCO)Cl2(-), in which uranyl, UO2(2+), is coordinated by one isocyanate and two chloride anion ligands. This activation of CO2 by a uranium(vi) nitride complex is distinctive from previous reports of oxidative insertion of CO2 into lower oxidation state U(iii) or U(iv) solid complexes, during which both C-O bonds remain intact. This unusual observation of spontaneous addition and activation of CO2 by NUOCl2(-) is a result of the high oxophilicity of uranium. If the computed Gibbs free energy of the reaction pathway, rather than the energy, is considered, there are barriers above the reactant asymptotes such that the observed reaction should not proceed under thermal conditions. This result provides a demonstration that energy rather than Gibbs free energy determines reactivity under low-pressure bimolecular conditions. PMID- 26898537 TI - Bioactive spirostanol saponins from the rhizome of Tupistra chinensis. AB - Phytochemical investigations of the rhizome of Tupistra chinensis led to the isolation of six new spirostanol saponins, one new spirostanol, along with eight known spirostanols. Their chemical structures were elucidated on the basis of spectroscopic and chemical methods, including IR, NMR, MS, and GC analyses. The antiproliferative effects against five human cancer cell lines were assayed for all the isolated compounds. Compounds 8, 12 and 15 showed potent cytotoxic activities against K562 cells. The isolated compounds were evaluated for their inhibitory activities on nitric oxide (NO) production induced by lipopolysaccharide in a macrophage cell line RAW 264.7. Compounds 2 and 12 showed significant inhibition on NO production with IC50 values of 16.1+/-1.8 and 13.5+/ 1.2 MUM, respectively. PMID- 26898536 TI - Comparing individual differences in inconsistency and plasticity as predictors of cognitive function in older adults. AB - INTRODUCTION: Recent theorizing differentiates key constraints on cognition, including one's current range of processing efficiency (i.e., flexibility or inconsistency) as well as the capacity to expand flexibility over time (i.e., plasticity). The present study uses intensive assessment of response time data to examine the interplay between markers of intraindividual variability (inconsistency) and gains across biweekly retest sessions (plasticity) in relation to age-related cognitive function. METHOD: Participants included 304 adults (aged 64 to 92 years: M = 74.02, SD = 5.95) from Project MIND, a longitudinal burst design study assessing performance across micro and macro intervals (response latency trials, weekly bursts, annual retests). For two reaction time (RT) measures (choice RT and one-back choice RT), baseline measures of RT inconsistency (intraindividual standard deviation, ISD, across trials at the first testing session) and plasticity (within-person performance gains in average RT across the 5 biweekly burst sessions) were computed and were then employed in linear mixed models as predictors of individual differences in cognitive function and longitudinal (6-year) rates of cognitive change. RESULTS: Independent of chronological age and years of education, higher RT inconsistency was associated uniformly with poorer cognitive function at baseline and with increased cognitive decline for measures of episodic memory and crystallized verbal ability. In contrast, predictive associations for plasticity were more modest for baseline cognitive function and were absent for 6-year cognitive change. CONCLUSIONS: These findings underscore the potential utility of response times for articulating inconsistency and plasticity as dynamic predictors of cognitive function in older adults. PMID- 26898538 TI - ER-alpha36, a novel variant of ERalpha, is involved in the regulation of Tamoxifen-sensitivity of glioblastoma cells. AB - Although accumulating evidence has confirmed that adjuvant Tamoxifen (TAM) treatment is able to sensitize glioblastoma cells to radiotherapy and inhibit their proliferation, TAM is not a suitable treatment for all types of glioblastoma cells; furthermore, long-term TAM usage may lead to TAM resistance. Therefore, understanding the underlying molecular mechanism of TAM resistance is necessary in order to improve TAM clinical therapy and the quality of life of patients suffering from glioblastomas. In this study, the significance of ER alpha36 to TAM resistance in glioblastoma cells was examined. First, an analysis of ER-alpha36 expression in two glioblastoma cell lines U87-MG and U251, showed that ER-alpha36 was anchored to the cytoplasmic membrane of these cells via Caveolin-1. Subsequent experiments investigating the mechanism of TAM-induced inhibition of U87-MG cell growth showed that TAM exerts its effect by inducing apoptosis via a down-regulation of Survivin expression and an up-regulation of Caspase-3 expression. Furthermore, TAM also arrested the cell cycle at S-phase. However, when U87-MG cells were preconditioned with an ER-alpha36-specific agonist, IC162, this neutralized TAM-induced inhibition of cell growth. This contrasted with the effect of ER-alpha36 depletion by RNAi, which enhanced TAM induced inhibition of cell growth. These findings suggest that resistance to TAM involves ER-alpha36, which probably acts as a negative regulator of TAM-induced inhibition of glioblastoma cell growth. These findings provide a novel insight into the basis of TAM resistance during glioblastoma therapy and a further study is underway to reveal more about the specific molecular mechanisms associated with ER-alpha36-mediated TAM resistance. PMID- 26898539 TI - Retinoid N-(1H-benzo[d]imidazol-2-yl)-5,5,8,8-tetramethyl-5,6,7,8 tetrahydronaphthalene-2-carboxamide induces p21-dependent senescence in breast cancer cells. AB - Retinoids have been implicated as pharmacological agents for the prevention and treatment of various types of cancers, including breast cancers. We analyzed 27 newly synthesized retinoids for their bioactivity on breast, liver, and colon cancer cells. Majority of the retinoids demonstrated selective bioactivity on breast cancer cells. Retinoid 17 had a significant inhibitory activity (IC50 3.5 MUM) only on breast cancer cells while no growth inhibition observed with liver and colon cancer cells. The breast cancer selective growth inhibitory action by retinoid 17 was defined as p21-dependent cell death, reminiscent of senescence, which is an indicator of targeted receptor mediated bioactivity. A comparative analysis of retinoid receptor gene expression levels in different breast cancer cells and IC50 values of 17 indicated the involvement of Retinoid X receptors in the cytotoxic bioactivity of retinoid 17 in the senescence associated cell death. Furthermore, siRNA knockdown studies with RXRgamma induced decrease in cell proliferation. Therefore, we suggest that retinoid derivatives that target RXRgamma, can be considered for breast cancer therapies. PMID- 26898540 TI - Methods for determination of fingernail steroids by LC/MS/MS and differences in their contents between right and left hands. AB - Fingernail clipping is expected to be a specimen for steroid testing, because it has several advantages over blood; i.e., noninvasive collection, ease of storage, portability and handling, and possibility for an assessment of the steroid status over a relatively long and retrospective time window. In this study, we examined whether there is a difference in the nail contents between the right and left hands for five steroids [glycochenodeoxycholic acid (GCDCA), taurochenodeoxycholic acid (TCDCA), dehydroepiandrosterone sulfate (DHEAS), testosterone (TST) and cortisol (CRT)] using newly developed liquid chromatography/electrospray ionization-tandem mass spectrometry methods. The nail contents between the hands were significantly different for GCDCA, TCDCA and DHEAS, whereas those of TST and CRT only slightly differed. These results might be due to the difference in the binding affinity of each steroid for the nail keratin. The relatively hydrophilic steroids, GCDCA, TCDCA and DHEAS, may be lost from nails in daily life due to their low affinity for keratin, which would produce differences in the nail contents between the hands. Thus, the fingernail GCDCA, TCDCA and DHEAS contents may be influenced by factors other than the disease; the nail analysis is inefficient in the diagnosis of the disease associated with these steroids. On the other hand, the nail analysis looks promising for evaluation of the status of TST and CRT, which are lipophilic and inferred to be tightly bound to the keratin. In fact, the nail TST content showed a significant sex difference, just like its serum/plasma concentration. PMID- 26898541 TI - Synthesis of 5alpha-androstane-3alpha,17beta-diol 17-O-glucuronide histaminyl conjugate for immunoassays. AB - Simple method of preparation of 5alpha-androstane-3alpha,17beta-diol 17-O glucuronide N-histaminyl amide was developed for the construction of immunoanalytical kit. Improved method of glucuronide derivative synthesis was used, followed by hydroxybenzotriazole-dicyclohexylcarbodiimide coupling with histamine. PMID- 26898543 TI - A New Scale for the Assessment of Competences in Cognitive and Behavioural Therapy. AB - BACKGROUND: Scales for assessing competence in CBT make an important contribution to research and practice. AIMS: To develop a novel scale. METHOD: A new structured assessment tool is described, which draws on a widely-used CBT competence framework to identify relevant areas of clinical practice. RESULTS: Scale content was clarified through piloting and review by a range of stakeholders. CONCLUSION: Pending formal testing of the psychometric properties, the scale is ready for use to assess competences in cognitive and behavioural therapy. PMID- 26898542 TI - The landscape of pain management in people with dementia living in care homes: a mixed methods study. AB - OBJECTIVES: The aim of this study is to explore the current landscape of pain management in people with dementia living in care home settings. Pain is extremely common in this patient group, yet there is very limited guidance for healthcare professionals. METHODS: Triangulation of stakeholder consultation and quality review of pain management guidance were performed. A review of existing pain management guidance was conducted using published quality criteria adapted for the field. Three focus group discussions were held with care home staff and two focus group discussions and an online survey with family carers. Data were subjected to thematic analysis to identify themes and sub-themes. Outcomes were reviewed by an expert panel, which gave recommendations. RESULTS: Fifteen existing guidelines were identified, of which three were designed for use in dementia and none were tailored for care home settings. Thematic analysis revealed six major themes in current pain management in dementia: importance of person-centredness, current lack of pain awareness in staff, communication as a core element, disparities in staff responsibility and confidence, the need for consistency of care and current lack of staff training. In addition to the needs for practice, the expert panel identified promising pharmacological treatment candidates, which warrant clinical evaluation. CONCLUSIONS: The findings of this study clearly articulate a need for an evidence-based pain management programme for care homes, which is informed by stakeholder input and based within a conceptual framework for this setting. There are novel opportunities for clinical trials of alternative analgesics for use in this patient group. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26898544 TI - Metallocene supported core@LDH catalysts for slurry phase ethylene polymerisation. AB - We report the synthesis of solid catalysts based on a zirconocene supported on either silica@AMO-LDH or zeolite@AMO-LDH for the slurry phase polymerisation of ethylene. The hybrid catalysts demonstrate synergistic effects in which the polymerisation activity is up to three times higher than the zirconocene supported on analogous single phase silica or zeolite supports. PMID- 26898545 TI - Development of a biphasic dissolution test for Deferasirox dispersible tablets and its application in establishing an in vitro-in vivo correlation. AB - In a biphasic dissolution medium, the integration of the in vitro dissolution of a drug in an aqueous phase and its subsequent partitioning into an organic phase is hypothesized to simulate the in vivo drug absorption. Such a methodology is expected to improve the probability of achieving a successful in vitro-in vivo correlation. Dissolution of Dispersible tablets of Deferasirox, a biopharmaceutics classification system type II compound, was studied in a biphasic dissolution medium using a flow-through dissolution apparatus coupled to a paddle apparatus. The experimental parameters associated with dissolution were optimized to discriminate between Deferasirox dispersible tablets of different formulations. The dissolution profiles obtained from this system were subsequently used to construct a level A in vitro-in vivo correlation. PMID- 26898546 TI - Exploring Factors Causing Low Brain Penetration of the Opioid Peptide DAMGO through Experimental Methods and Modeling. AB - To advance the development of peptide analogues for improved treatment of pain, we need to learn more about the blood-brain barrier transport of these substances. A low penetration into the brain, with an unbound brain to blood ratio, Kp,uu, of 0.08, is an important reason for the lack of effect of the enkephalin analogue DAMGO (H-Tyr-d-Ala-Gly-MePhe-Gly-ol) according to earlier findings. The aim of this study was to investigate the role of efflux transporters, metabolism in the brain, and/or elimination through interstitial fluid bulk flow for the brain exposure of DAMGO. The in vivo brain distribution of DAMGO was evaluated using microdialysis in the rat. Data were analyzed with population modeling which resulted in a clearance into the brain of 1.1 and an efflux clearance 14 MUL/min/g_brain. The efflux clearance was thus much higher than the bulk flow known from the literature. Coadministration with the efflux transporter inhibitors cyclosporin A and elacridar in vivo did not affect Kp,uu. The permeability of DAMGO in the Caco-2 assay was very low, of the same size as mannitol. The efflux ratio was <2 and not influenced by cyclosporin A or elacridar. These results indicate that the well-known efflux transporters Pgp and Bcrp are not responsible for the higher efflux of DAMGO, which opens up for an important role of other transporters at the BBB. PMID- 26898547 TI - Systemic availability of guanidinoacetate affects GABAA receptor function and seizure threshold in GAMT deficient mice. AB - Deficiency of guanidinoacetate methyltransferase (GAMT) causes creatine depletion and guanidinoacetate accumulation in brain with the latter deemed to be responsible for the severe seizure disorder seen in affected patients. We studied electrical brain activity and GABAA mediated mechanisms of B6J.Cg-Gamt(tm1Isb) mice. Electrocorticographic (ECoG) monitoring of pharmacological treatments with ornithine (5 % in drinking water for 5-18 days) and/or Picrotoxin (PTX) (a GABAA receptor antagonist) (1.5 mg/kg, I.P.) in Gamt(MUT) and Gamt(WT) groups [n = 3, mean age (SEM) = 6.9 (0.2) weeks]. Mice were fitted with two frontal and two parietal epidural electrodes under ketamine/xylazine anesthesia. Baseline and test recordings were performed for determination of seizure activity over a 2 h period. The ECoG baseline of Gamt(MUT) exhibited an abnormal monotonous cortical rhythm (7-8 Hz) with little variability during awake and sleep states compared to wild type recordings. Ornithine treatment and also PTX administration led to a relative normalization of the Gamt(MUT) ECoG phenotype. Gamt(WT) on PTX exhibited electro-behavioral seizures, whereas the Gamt(MUT) did not have PTX induced seizures at the same PTX dose. Gamt(MUT) treated with both ornithine and PTX did not show electro-behavioral seizures while ornithine elevated the PTX seizure threshold of Gamt(MUT) mice even further. These data demonstrate: (1) that there is expression of electrical seizure activity in this Gamt-deficient transgenic mouse strain, and (2) that the systemic availability of guanidinoacetate affects GABAA receptor function and seizure thresholds. These findings are directly and clinically relevant for patients with a creatine-deficiency syndrome due to genetic defects in GAMT and provide a rational basis for a combined ornithine/picrotoxin therapeutic intervention. PMID- 26898548 TI - Creatine for women: a review of the relationship between creatine and the reproductive cycle and female-specific benefits of creatine therapy. AB - The creatine/phosphocreatine/creatine kinase circuit is instrumental in regulating high-energy phosphate metabolism, and the maintenance of cellular energy turnover. The mechanisms by which creatine is able to buffer and regulate cellular energy balance, maintain acid-base balance, and reduce the effects of oxidative stress have led to a large number of studies into the use of creatine supplementation in exercise performance and to treat diseases associated with cellular energy depletion. Some of these studies have identified sex-specific responses to creatine supplementation, as such; there is the perception, that females might be less receptive to the benefits of creatine supplementation and therapy, compared to males. This review will describe the differences in male and female physique and physiology that may account for such differences, and discuss the apparent endocrine modulation of creatine metabolism in females. Hormone driven changes to endogenous creatine synthesis, creatine transport and creatine kinase expression suggest that significant changes in this cellular energy circuit occur during specific stages of a female's reproductive life, including pregnancy and menopause. Recent studies suggest that creatine supplementation may be highly beneficial for women under certain conditions, such as depression. A greater understanding of these pathways, and the consequences of alterations to creatine bioavailability in females are needed to ensure that creatine is used to full advantage as a dietary supplement to optimize and enhance health outcomes for women. PMID- 26898549 TI - Identification of repetitive units in protein structures with ReUPred. AB - Over the last decade, numerous studies have demonstrated the fundamental importance of tandem repeat (TR) proteins in many biological processes. A plethora of new repeat structures have also been solved. The recently published RepeatsDB provides information on TR proteins. However, a detailed structural characterization of repetitive elements is largely missing, as repeat unit annotation is manually curated and currently covers only 3 % of the bona fide TR proteins. Repeat Protein Unit Predictor (ReUPred) is a novel method for the fast automatic prediction of repeat units and repeat classification using an extensive Structure Repeat Unit Library (SRUL) derived from RepeatsDB. ReUPred uses an iterative structural search against the SRUL to find repetitive units. On a test set of solenoid proteins, ReUPred is able to correctly detect 92 % of the proteins. Unlike previous methods, it is also able to correctly classify solenoid repeats in 89 % of cases. It also outperforms two recent state-of-the-art methods for the repeat unit identification problem. The accurate prediction of repeat units increases the number of annotated repeat units by an order of magnitude compared to the sequence-based Pfam classification. ReUPred is implemented in Python for Linux and freely available from the URL: http://protein.bio.unipd.it/reupred/ . PMID- 26898550 TI - A combination of serum iron, ferritin and transferrin predicts outcome in patients with intracerebral hemorrhage. AB - Association of a high-serum ferritin with poor outcome showed that iron might play a detrimental role in the brain after intracerebral hemorrhage (ICH). Here, we investigated changes in serum iron, ferritin, transferrin (Tf) and ceruloplasmin (CP) in patients with ICH (n = 100) at day 1 (admission), 3, 7, 14 and 21 and those in control subjects (n = 75). The hematoma and edema volumes were also determined in ICH-patients on admission and at day 3. The Modified Rankin Scale (mRS) of 59 patients was >=3 (poor outcome) and 41 < 3 (good outcome) at day 90. Serum ferritin was significantly higher and serum iron and Tf markedly lower in patients with poor-outcome than the corresponding values in patients with good-outcome at day 1 to 7 and those in the controls. There was a significant positive correlation between serum ferritin and relative edema volume or ratio at day 1 and 3 and hematoma volume at day 1 (n = 28), and a negative correlation between serum iron or Tf and hematoma volume at day 1 (n = 100). We concluded that not only increased serum ferritin but also reduced serum iron and Tf are associated with outcome as well as hematoma volume. PMID- 26898551 TI - Vascular and Metabolic Factors in Alzheimer's Disease and Related Dementias: Introduction. PMID- 26898552 TI - The Utility of Cerebral Blood Flow as a Biomarker of Preclinical Alzheimer's Disease. AB - There is accumulating evidence suggesting that changes in brain perfusion are present long before the clinical symptoms of Alzheimer's disease (AD), perhaps even before amyloid-beta accumulation or brain atrophy. This evidence, consistent with the vascular hypothesis of AD, implicates cerebral blood flow (CBF) in the pathogenesis of AD and suggests its utility as a biomarker of preclinical AD. The extended preclinical phase of AD holds particular significance for disease modification, as treatment would likely be most effective in this early asymptomatic stage of disease. This highlights the importance of identifying reliable and accurate biomarkers of AD that can differentiate normal aging from preclinical AD prior to clinical symptom manifestation. Cerebral perfusion, as measured by arterial spin labeling magnetic resonance imaging (ASL-MRI), has been shown to distinguish between normal controls and adults with AD. In addition to demonstrating diagnostic utility, CBF has shown usefulness as a tool for identifying those who are at risk for AD and for predicting subtle cognitive decline and conversion to mild cognitive impairment and AD. Taken together, this evidence not only implicates CBF as a useful biomarker for tracking disease severity and progression, but also suggests that ASL-measured CBF may be useful for identifying candidates for future AD treatment trials, especially in the preclinical, asymptomatic phases of the disease. PMID- 26898555 TI - Mismatch response (MMR) in neonates: Beyond refractoriness. AB - In the adult auditory system, deviant detection and updating the representation of the environment is reflected by the event-related potential (ERP) component termed the mismatch negativity (MMN). MMN is elicited when a rare-pitch deviant stimulus is presented amongst frequent standard pitch stimuli. The same stimuli also elicit a similar discriminative ERP component in sleeping newborn infants (termed the mismatch response: MMR). Both the MMN and the MMR can be confounded by responses generated by differential refractoriness of frequency-selective neural populations. Employing a stimulus paradigm designed to minimize this confounding effect, newborns were presented with sequences of pure tones under two conditions: In the oddball block, rare deviant tones (500Hz; 10%) were delivered amongst frequent standards (700Hz; 90%). In the control block, a comparison tone (500Hz) was presented with the same probability as the deviant (10%) along with the four contextual tones (700Hz, 980Hz, 1372Hz, 1920.8Hz; 22.5% each). The significant difference found between the response elicited by the deviant and the comparison tone showed that the response elicited by the deviant in the oddball sequences cannot be fully explained by frequency-specific refractoriness of the neural generators. This shows that neonates process sounds in a context-dependent manner as well as strengthens the correspondence between the adult MMN and the infant MMR. PMID- 26898554 TI - Dose-dependent response of Trichoderma harzianum in improving drought tolerance in rice genotypes. AB - MAIN CONCLUSION: This study demonstrates a dose-dependent response of Trichoderma harzianum Th-56 in improving drought tolerance in rice by modulating proline, SOD, lipid peroxidation product and DHN / AQU transcript level, and the growth attributes. In the present study, the effect of colonization of different doses of T. harzianum Th-56 strain in rice genotypes were evaluated under drought stress. The rice genotypes treated with increasing dose of T. harzianum strain Th 56 showed better drought tolerance as compared with untreated control plant. There was significant change in malondialdehyde, proline, higher superoxide dismutase level, plant height, total dry matter, relative chlorophyll content, leaf rolling, leaf tip burn, and the number of scorched/senesced leaves in T. harzianum Th-56 treated rice genotypes under drought stress. This was corroborated with altered expression of aquaporin and dehydrin genes in T. harzianum Th-56 treated rice genotypes. The present findings suggest that a dose of 30 g/L was the most effective in improving drought tolerance in rice, and its potential exploitation will contribute to the advancement of rice genotypes to sustain crop productivity under drought stress. Interaction studies of T. harzianum with three aromatic rice genotypes suggested that PSD-17 was highly benefitted from T. harzianum colonization under drought stress. PMID- 26898553 TI - Strigolactone versus gibberellin signaling: reemerging concepts? AB - MAIN CONCLUSION: In this review, we compare knowledge about the recently discovered strigolactone signaling pathway and the well established gibberellin signaling pathway to identify gaps of knowledge and putative research directions in strigolactone biology. Communication between and inside cells is integral for the vitality of living organisms. Hormonal signaling cascades form a large part of this communication and an understanding of both their complexity and interactive nature is only beginning to emerge. In plants, the strigolactone (SL) signaling pathway is the most recent addition to the classically acting group of hormones and, although fundamental insights have been made, knowledge about the nature and impact of SL signaling is still cursory. This narrow understanding is in spite of the fact that SLs influence a specific spectrum of processes, which includes shoot branching and root system architecture in response, partly, to environmental stimuli. This makes these hormones ideal tools for understanding the coordination of plant growth processes, mechanisms of long-distance communication and developmental plasticity. Here, we summarize current knowledge about SL signaling and employ the well-characterized gibberellin (GA) signaling pathway as a scaffold to highlight emerging features as well as gaps in our knowledge in this context. GA signaling is particularly suitable for this comparison because both signaling cascades share key features of hormone perception and of immediate downstream events. Therefore, our comparative view demonstrates the possible level of complexity and regulatory interfaces of SL signaling. PMID- 26898556 TI - Practical Approaches to the Management of Dual Refractory Multiple Myeloma. AB - The outcome of myeloma patients' dual refractory to lenalidomide and bortezomib is generally poor and represents a significant clinical challenge with a clear need for new therapeutic approaches. This has prompted the development of next generation proteasome inhibitors and immunodulatory drugs (IMiDs), as well as new classes of drugs with novel mechanisms of action. As a result, several of these agents have received regulatory approval that have shown promising activity in the dual refractory setting including the second-generation proteasome inhibitor carfilzomib and third-generation IMiD pomalidomide. Moreover, the regulatory approval of several first-in-class drugs for myeloma such as the histone deacetylase (HDAC) inhibitor panobinostat and the anti-CD38 monoclonal antibody daratumumab has further broadened the therapeutic landscape for these patients. Collectively, these advances have provided new treatment strategies in dual refractory myeloma as well as important insights for the development of future studies with rationally designed drug combinations to target this challenging patient population. PMID- 26898559 TI - Enhancement of binding kinetics on affinity substrates by laser point heating induced transport. AB - Enhancing the time response and detection limit of affinity-binding based biosensors is an area of active research. For diffusion limited reactions, introducing active mass transport is an effective strategy to reduce the equilibration time and improve surface binding. Here, a laser is focused on the ceiling of a microchamber to generate point heating, which introduces natural advection and thermophoresis to promote mass transport to the reactive floor. We first used the COMSOL simulation to study how the kinetics of ligand binding is influenced by the optothermal effect. Afterwards, binding of biotinylated nanoparticles to NeutrAvidin-treated substrates is quantitatively measured with and without laser heating. It is discovered that laser induced point heating reduces the reaction half-life locally, and the reduction improves with the natural advection velocity. In addition, non-uniform ligand binding on the substrate is induced by the laser with predictable binding patterns. This optothermal strategy holds promise to improve the time-response and sensitivity of biosensors and microarrays. PMID- 26898557 TI - Minimal Residual Disease Assessment in the Context of Multiple Myeloma Treatment. AB - With contemporary therapeutic strategies in multiple myeloma, heretofore unseen depth and rate of responses are being achieved. These strategies have paralleled improvements in outcome of multiple myeloma patients. The integration of the next generation of proteasome inhibitors and antibody therapeutics promise continued improvements in therapy with the expectation of consistent depth of response not quantifiable by current clinical methods. As such, there is a growing need to develop adequate tools to evaluate deeper disease response after therapy and to refine the response criteria including the minimal residual disease. Several emerging techniques are being evaluated for these purposes including multi parameter flow cytometry, allele-specific oligonucleotide polymerase chain reaction, next-generation sequencing, and imaging modalities. In this review, we highlight the recent developments and evaluate advantages and limitations of the current technologies to assess minimal residual disease. We also discuss future applications of these methodologies in potentially guiding multiple myeloma treatment decisions. PMID- 26898560 TI - Porous films by the self-assembly of inorganic rod-b-coil block copolymers: mechanistic insights into the vesicle-to-pore morphological evolution. AB - The self-assembly in thin films of polyphosphazene block copolymers [N = P(O2C12H8)]n-b-[N = PMePh]m (O2C12H8 = 2,2'-dioxy-1,1'-biphenyl; : n = 50, m = 35; : n = 20, m = 70, and : n = 245, m = 60), having different volume fractions of the rigid [N = P(O2C12H8)]n block, has been studied. BCP spontaneously self assembled into well-defined round-shaped macroporous films, observing also, as a minor morphology, spherical vesicles in regions where the film was not formed. A detailed study by SEM, TEM and AFM of the structure of the vesicles, the morphology of the pores (inverted mushroom-shaped), and the behaviour of the copolymers with shorter () and longer () [N = P(O2C12H8)]n rigid blocks provided sufficient experimental evidence to propose a vesicle-to-pore morphological evolution as the most likely mechanism to explain the pore formation during the self-assembly of . Moreover, by changing the volume fraction of the rigid block and the speed of solvent evaporation, it was possible to vary the pore morphology (and their diameter) from isolated regular groups to 3D interconnected pore networks. PMID- 26898558 TI - Most prevalent unmet supportive care needs and quality of life of breast cancer patients in a tertiary hospital in Malaysia. AB - BACKGROUND: Addressing breast cancer patients' unmet supportive care needs in the early stage of their survivorship have become a prime concern because of its significant association with poor quality of life (QOL), which in turn increases healthcare utilization and costs. There is no study about unmet supportive care needs of breast cancer patients in Malaysia. This study aims to assess the most prevalent unmet supportive care needs of Malaysian breast cancer patients and the association between QOL and patients' characteristics, and their unmet supportive care needs. METHODS: A cross-sectional study was conducted at the Surgery and Oncology Clinic between May 2014 and June 2014 in a tertiary hospital in Malaysia. A total of 117 patients out of 133 breast cancer patients recruited by universal sampling were interviewed using a structured questionnaire consisted of three parts: participants' socio-demographic and disease characteristics, Supportive Care Needs Survey-Short Form Questionnaire (SCNS-SF34) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30). RESULTS: The highest unmet supportive care needs were observed in the psychological domain (Mean 53.31; SD +/- 21.79), followed by physical domain (Mean 38.16; SD +/- 27.15). Most prevalent unmet supportive care needs were uncertainty about the future (78.6 %), fears about the cancer spreading (76.1 %), feelings of sadness (69.2 %), feelings about death and dying (68.4 %), concerns about those close to the patient (65.0 %) and feeling down or depressed (65.0 %). Multivariate linear analysis showed that early breast cancer survivors diagnosed at an advanced stage and with greater physical and psychological needs were significantly (p < 0.05) associated with poorer QOL. CONCLUSION: Most prevalent unmet needs among Malaysian breast cancer patients were found in the psychological domain. Early breast cancer survivors with late stage diagnosis who had more unmet needs in psychological and physical domains were more likely to have a poor QOL. PMID- 26898561 TI - Comparison of Mechanical and Indirect Ultrasonic Placement Technique on Mineral Trioxide Aggregate Retrofill Density in Simulated Root-end Surgery. AB - INTRODUCTION: The objective of this study was to evaluate the density of mineral trioxide aggregate (MTA) root-end filling placed by either manual condensation or manual condensation with indirect ultrasonic activation under simulated root-end surgery conditions in vitro. METHODS: Extracted human molar teeth were obtained and sectioned to provide single-rooted samples (n = 50). Roots were instrumented to a size of 40 with a .04 taper and obturated with a warm vertical technique. The coronal end of each root was embedded in resin. A root-end resection and root end preparation were completed on each root. Samples were randomly assigned to receive root-end fillings with ProRoot MTA (Dentsply, Tulsa, OK) by 1 of 2 techniques: manual condensation alone (group M, n = 25) or manual condensation with indirect ultrasonic activation (group U, n = 25). MTA was placed incrementally to the level of the root end using the enumerated technique. Samples were weighed immediately before and after filling placement. MTA was removed from all samples so as not to change the root-end preparation, rinsed, and dried. Each sample then underwent MTA placement by the opposite technique, and weight was again measured immediately before and after MTA placement. MTA filling weights for each technique were analyzed statistically using a technique for repeated measures analysis. Statistical analysis was conducted to account for any carryover or order effects. RESULTS: After adjustment for carryover effects, it was found that regardless of the order of placement, the mean fill weight of MTA produced by the indirect ultrasonic method was on average 4.42 mg heavier than that produced by manual condensation alone. This result was statistically significant (P < .0003). CONCLUSIONS: Under simulated root-end surgery conditions, indirect ultrasonic condensation of MTA root-end fillings was shown to produce a filling that was significantly denser than MTA placed by manual condensation alone. PMID- 26898562 TI - Effects of Recombinant Overexpression of Bcl2 on the Proliferation, Apoptosis, and Osteogenic/Odontogenic Differentiation Potential of Dental Pulp Stem Cells. AB - INTRODUCTION: The therapeutic usefulness of dental pulp stem cells (DPSCs) is severely limited by low survivability upon transplantation in situ because of the presence of various proapoptotic factors within damaged/diseased tissues (ie, hypoxia and inflammation). One strategy to enhance the survivability of grafted DPSCs could be recombinant overexpression of antiapoptotic genes, such as the B cell lymphoma 2 gene (Bcl2). METHODS: DPSCs were transfected with the Bcl2 and/or GFP gene. Cell density and mitotic activity of transfected DPSCs within in vitro culture were evaluated with the water soluble tetrazolium salt-8 (WST-8) and bromodeoxyuridine assay, respectively, whereas apoptosis was evaluated through the detection of cytoplasmic histone-associated DNA fragments. The osteogenic/odontogenic differentiation potential of these cells was evaluated with quantitative real-time polymerase chain reaction, alkaline phosphatase, and alizarin red staining. RESULTS: Bcl2-transfected DPSCs exhibited consistently higher cell densities than the GFP-transfected control within in vitro culture, and this was not because of the higher mitotic rate but was instead attributed to enhanced cell survivability because of the inhibition of apoptosis by Bcl2. Recombinant overexpression of Bcl2 inhibited the osteogenic/odontogenic potential of DPSCs, as indicated by lower levels of alkaline phosphatase activity and mineralized calcium deposition, together with the down-regulated expression of several key osteogenic/odontogenic gene markers including collagen I, osteocalcin, dentin matrix protein-1, bone sialoprotein, and alkaline phosphatase. CONCLUSIONS: The results place a "caveat" or limitation on the use of recombinant Bcl2 overexpression as a therapeutic strategy for improving the survivability of grafted DPSCs in that the osteogenic/odontogenic potential of these cells may be compromised despite enhanced survival within the host. PMID- 26898563 TI - Hypertension Undermines Mineralization-inducing Capacity of and Tissue Response to Mineral Trioxide Aggregate Endodontic Cement. AB - INTRODUCTION: This study evaluated the effect of hypertension on tissue response to and mineralization capacity of white and gray mineral trioxide aggregate (MTA) (Angelus Industry Ontological Products, Londrina, Brazil), an endodontic reparative cement. METHODS: Polyethylene tubes containing gray MTA, white MTA, or intermediate restorative material (positive control) or an empty tube (negative control) were implanted into the dorsal connective tissue of spontaneous hypertensive and Wistar rats (n = 12 each). Six rats in each group were sacrificed after 7 days, and the remainder after 30 days. Tubes with surrounding tissue were removed, and a histologic analysis was performed using hematoxylin eosin and von Kossa staining and examination by polarized light microscopy. RESULTS: The inflammatory response to all materials was greater in hypertensive compared with normotensive rats (P < .05). Positive von Kossa staining and birefringent structures in polarized light were observed for both gray and white MTA (P > .05), but these were more pronounced in normotensive rats (P < .05). Necrotic areas with positive von Kossa staining were observed for intermediate restorative material. CONCLUSIONS: Hypertension undermines tissue repair and mineralization, which can negatively affect treatment outcome. Nonetheless, mineralization in response to MTA was observed even under hypertensive conditions. PMID- 26898564 TI - Dentinal Tubule Penetration of Tricalcium Silicate Sealers. AB - INTRODUCTION: The treatments for which mineral trioxide aggregate (MTA)-based materials can be used in dentistry are expanding. Smaller particle size and easier handling properties have allowed the advent of tricalcium silicate sealers including EndoSequence BC Sealer (Brasseler USA, Savannah, GA), QuickSet2 (Avalon Biomed, Bradenton, FL), NeoMTA Plus (Avalon Biomed), and MTA Fillapex (Angelus, Londrina, Brazil). The objective of this study was to measure the tubule penetration with these sealers using continuous wave (CW) and single-cone (SC) obturation techniques. METHODS: Eighty single-rooted teeth were randomly divided into 8 groups of 10 and obturated with 1 of the previously mentioned sealers mixed with trace amounts of rhodamine using either the CW or SC technique. Teeth were sectioned at 1 mm and 5 mm from the apex and examined under a confocal laser microscope. The percentage of sealer penetration and the maximum sealer penetration were measured. RESULTS: The tricalcium silicate sealers penetrated tubules as deep as 2000 MUm (2 mm). The percentage of sealer penetration was much higher 5 mm from the apex, with many specimens having 100% penetration for both SC and warm vertical techniques. MTA Fillapex, a resin-based sealer with less than 20% MTA particles, had significantly greater tubule penetration with a warm vertical technique versus the SC technique at the 1-mm level. CONCLUSIONS: Within the limitations of this study, the CW and SC techniques produced similar tubule penetration at both the 1-mm and the 5-mm level with the tricalcium silicate sealers BC Sealer, QuickSet2, and NeoMTA Plus. PMID- 26898565 TI - Efficacy of Different Nickel-Titanium Instruments in Removing Gutta-percha during Root Canal Retreatment. AB - INTRODUCTION: The aim of this study was to compare the cleanliness of root canal walls after retreatment using ProTaper Next (PTN; Dentsply Maillefer, Ballaigues, Switzerland), Twisted File Adaptive (TFA; Axis/SybronEndo, Orange, CA), Reciproc (PRC; VDW, Munich, Germany), and ProTaper Universal retreatment (PTR, Dentsply Maillefer) nickel-titanium systems and the time required for gutta-percha and sealer removal. METHODS: Eighty human maxillary central incisors with single and straight root canals were instrumented up to #40.02 with manual K-files (Dentsply Maillefer) and obturated using the continuous wave of condensation technique. Removal of the gutta-percha and sealer was performed using 1 of the following nickel-titanium systems: PTN, TFA, RPC, or PTR. The teeth were sectioned, and digital images were captured. The photographs were analyzed using AutoCAD software (Autodesk, San Rafael, CA). Also, the total time required for gutta percha removal was calculated by a chronometer. RESULTS: The total retreatment time was significantly shorter in the PTR group compared with the other groups (P < .05). There was a significant difference between the groups according to the total residual gutta-percha and sealer (P < .05). The PTN and PTR groups left significantly less gutta-percha and sealer remnant than the TFA and RPC groups (P < .05). CONCLUSIONS: Within the limitations of this study, the PTN and the PTR groups showed less residual gutta-percha and sealer than the TFA and RPC groups. The time required for gutta-percha and sealer removal was similar for all the groups, except for the PTR group. PMID- 26898567 TI - Periapical Bone Healing after Apicectomy with and without Retrograde Root Filling with Mineral Trioxide Aggregate: A 6-year Follow-up of a Randomized Controlled Trial. AB - INTRODUCTION: In cases of post-treatment periapical disease, retreatment may be necessary. To choose the most appropriate retreatment method, knowledge of the long-term prognosis is important. Surgical endodontic retreatment (SER) is a relevant treatment method. This study assessed changes in outcome from 1 to 6 years after surgery. METHODS: SER was performed on teeth randomly allocated to have a MTA root-end filling (MTA group) or smoothing of the orthograde gutta percha filling after apicectomy (GP group). Patients participating in the 1-year follow-up were reinvited for a 6-year clinical and radiographic examination. Three observers assessed treatment outcome both clinically and radiographically from the 1-year and 6-year follow-up examination. RESULTS: At the 6-year follow up, 39 of 52 teeth were available and examined (75% participation rate). In the MTA group, 16 of 19 teeth (86%) and in the GP group 11 of 20 teeth (55%) were assessed as successful (P = .04). In the MTA group and the GP group, 80% and 90%, respectively, of teeth assessed as successful at the 1-year follow-up remained successful. All unsuccessful teeth in the MTA group (3 teeth) were lost because of vertical root fracture. CONCLUSIONS: The proportion of healed cases was larger in the MTA group than in the GP group at both the 1-year and 6-year follow-up. Findings indicate that a 1-year follow-up may not be sufficient in assessing the long-term outcome of surgical endodontic retreatment. With a longer follow-up, other factors not directly related to the endodontic treatment may be relevant for a successful outcome. This needs further investigation in larger patient samples. PMID- 26898566 TI - Variability in Capsaicin-stimulated Calcitonin Gene-related Peptide Release from Human Dental Pulp. AB - INTRODUCTION: The unique innervation and anatomic features of dental pulp contribute to the remarkable finding that any physical stimulation of pulpal tissue is painful. Furthermore, when pathological processes such as caries affect teeth and produce inflammation of the pulp, the pain experienced can be quite intense and debilitating. To better understand these underlying neurobiological mechanisms and identify novel analgesic targets for pulpally derived pain, we have developed a powerful ex vivo model using human tooth slices. METHODS: Noncarious, freshly extracted teeth were collected and sectioned longitudinally into 1-mm-thick slices containing both dental pulp and the surrounding mineralized tissues. Tooth slices from 36 patients were exposed to 60 MUmol/L capsaicin to stimulate the release of calcitonin gene-related peptide (CGRP) from nerve terminals in the pulp. Patient factors were analyzed for their effects on capsaicin-stimulated CGRP release using a mixed model analysis of variance. RESULTS: Approximately one third of the variability observed in capsaicin-evoked CGRP release was attributable to differences between individuals. In terms of individual factors, there was no effect of anesthesia type, sex, or age on capsaicin-stimulated CGRP release. Using a within-subject study design, a significant effect of capsaicin on CGRP release was observed. CONCLUSIONS: Capsaicin-stimulated CGRP release from dental pulp is highly variable between individuals. A within-subject study design improves the variability and maximizes the potential of this powerful translational model to test the efficacy of novel pharmacotherapeutic agents on human peripheral nociceptors. PMID- 26898568 TI - Effect of carbamazepine on dolutegravir pharmacokinetics and dosing recommendation. AB - PURPOSE: Dolutegravir (DTG) is primarily metabolized by UGT1A1 with CYP3A as a minor route. Carbamazepine (CBZ) is a potent inducer of these enzymes; thus, the effect of oral extended-release CBZ on DTG pharmacokinetics (PK) was evaluated to provide dose recommendation when co-administered. METHODS: This was a single center, open-label, fixed-sequence, crossover study in healthy adults. Subjects received three treatments: DTG 50 mg every 24 h (q24h) * 5 days in period 1, followed by CBZ 100 mg every 12 h (q12h) * 3 days, then 200 mg q12h * 3 days, then 300 mg q12h * 10 days in period 2, and DTG 50 mg q24h + CBZ 300 mg q12h * 5 days in period 3. No washout intervals occurred. Each dose was administered with a moderate-fat meal. Serial PK samples for DTG were collected on day 5 of periods 1 and 3. Plasma DTG PK parameters were determined with non-compartmental analysis. Geometric least-squares mean ratios (GMRs) and 90 % confidence intervals (CIs) were generated by the mixed-effect model for within-subject treatment comparisons. Safety assessments were performed throughout the study. RESULTS: Sixteen subjects enrolled; 14 completed the study. CBZ significantly reduced DTG exposure: GMRs (90 % CI) for DTG + CBZ versus DTG alone were 0.51 (0.48-0.549), 0.67 (0.61-0.73), and 0.27 (0.24-0.31) for area under the curve from time zero to the end of the dosing interval (AUC(0-tau)), maximum observed plasma concentration (Cmax), and plasma concentration at the end of the dosing interval (Ctau), respectively. DTG alone and co-administered with CBZ was well tolerated. CONCLUSION: Integrase strand transfer inhibitor-naive subjects taking CBZ should receive DTG 50 mg twice daily versus once daily, as is recommended with other potent UGT1A/CYP3A inducers. ClinicalTrials.gov: NCT01967771. PMID- 26898569 TI - Mesalazine Modified-Release Tablet in the Treatment of Ulcerative Colitis in the Active Phase: A Chinese, Multicenter, Single-Blind, Randomized Controlled Study. AB - INTRODUCTION: This study compared the efficacy and safety of two mesalazine formulations in the treatment of Chinese patients with mildly to moderately active ulcerative colitis (UC). METHODS: In this multicenter, single-blind, randomized controlled study of 251 patients with active UC conducted from November 2010 to January 2012, subjects were randomized to treatment with mesalazine modified-release tablets (MR group, n = 123) or enteric-coated tablets (EC group, n = 128) at 800 mg three-times daily for 8 weeks. The primary efficacy measure was the decrease in UC Disease Activity Index (UCDAI) at final evaluation. If the 95% confidence interval (CI) lower limit of the difference of the decrease in UCDAI between groups was over -1.0, mesalazine modified-release tablets were considered non-inferior to mesalazine enteric-coated tablets. The change in UCDAI in patients with mild and moderate (UCDAI 3-5 and 6-8 at enrollment, respectively) UC was analyzed. Secondary efficacy measures were remission and efficacy rates. Incidences of adverse drug reactions (ADRs) were calculated. RESULTS: The decreases in UCDAI at final evaluation were 2.84 and 2.56 in the MR and EC groups, respectively, with a difference of 0.27 between groups (95% CI -0.34, 0.88). The remission rates were 48.33% (58/120) and 55.65% (69/124), and the efficacy rates were 63.33% (76/120) and 66.94% (83/124) in the MR and EC groups, respectively (all P > 0.05). In patients with mild UC, the decreases in UCDAI were 2.16 and 2.05 in the MR and EC groups, respectively, while in patients with moderate UC they were 3.49 and 3.03, respectively (all P > 0.05). The incidences of ADRs in the MR and EC groups were 6.61% (8/121) and 10.24% (13/127), respectively (P > 0.05). No serious ADRs were reported during the study. CONCLUSION: Mesalazine modified-release tablets are non-inferior to enteric-coated tablets and are an effective and safe treatment option in Chinese patients with mildly to moderately active UC. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01257386. FUNDING: Tillotts Pharma AG. PMID- 26898570 TI - Rutin as a Natural Therapy for Alzheimer's Disease: Insights into its Mechanisms of Action. AB - Rutin (quercetin-3-O-rutinoside) is a multifunctional natural flavonoid glycoside with profound effects on the various cellular functions under pathological conditions. Due to the ability of rutin and/or its metabolites to cross the blood brain barrier, it has also been shown to modify the cognitive and various behavioral symptoms of neurodegenerative diseases. In this review, its therapeutic potential for Alzheimer's disease (AD) is evaluated through appraisal of current literatures relevant to the various cellular and molecular targets of the disease. Among the most relevant mechanisms involved are effect on amyloid beta (Abeta) processing, aggregation and action; alteration of the oxidant antioxidant balance associated with neuronal cell loss; removing the inflammatory component of neurodegeneration, etc. The effect of rutin resulting from its physicochemical features related to effects like metal chelation and bioavailability are also discussed. PMID- 26898571 TI - Role of Isoprenoid Compounds on Angiogenic Regulation: Opportunities and Challenges. AB - Isoprenoids represent one of the largest classes of phytochemicals. The structural diversity of these compounds, as well as their remarkable biological activities, makes them suitable candidates for the development of novel therapeutic agents. Several isoprenoids have demonstrated promising potential in the modulation of angiogenesis processes, and therefore provide an appealing alternative and/or addition to the available pharmacotherapies. These compounds could be used per se or combined with standard therapies, which can potentially reduce the undesired secondary effects. Compounds like the sesquiterpenoid artemisinin, and its derivatives, or the diterpenoid triptolide have been successfully tested in a broad range of models (in vitro and in vivo). Moreover, sesquiterpenoids seem to be a promising resource of natural angiogenic modulators, as it can be attested by the significant number of recent publications in this subject. On the other hand, other isoprenoids, such as the triterpenoid ursolic acid, are still under-explored and further studies are needed to understand their role within angiogenic process. Further insights into isoprenoids mode of action in angiogenesis will hopefully pave the way towards their successful clinical use. PMID- 26898572 TI - The Possible Role of Infertility Drugs in Later Malignancy: A Review. AB - BACKGROUND: Some 15% of all couples in the industrialized world suffer from infertility. Accordingly, any possible life-long morbidity that may result from treatments for infertility presents a significant concern to public health. The use of medications for infertility is specifically relevant to their possible effects on the classical target tissues for hormones involved in the sex axes, i.e., uterus, ovaries, and breast, but may have an effect on other organs, which harbor receptors for some of the hormones involved in reproduction. When one deals with the effect of treatment for infertility on the occurrence of malignant conditions, there is no doubt that certain malignancies tend to occur more frequently in women who suffered from and/or were treated for infertility. OBJECTIVE: To review the accumulated data on the association of treatments for infertility with subsequent malignancies both in the classical target organs of sex steroids and in non-target organs. METHODS: Systematic compilation of the relevant literature. RESULTS & CONCLUSION: Contrary to popular believes, treatment for infertility is associated with very little increase in malignacies. PMID- 26898573 TI - Chiral N-Phosphonyl Imines for an Aza-Morita-Baylis-Hillman Reaction via Group Assisted Purification (GAP) Chemistry. AB - Seventeen examples of aza-Morita-Baylis-Hillman (aza-MBH) adducts have been synthesized by reacting chiral N-phosphonyl imines with acrylonitrile in good to excellent yields (up to 96%) and high diastereoselectivity (up to 99:1 dr). The synthesis of these adducts followed the method of group-assisted purification (GAP) chemistry, in which the pure aza-MBH products were readily obtained by washing the crude products with cosolvents of hexane and ethyl acetate. PMID- 26898575 TI - Emotional and personality changes following brain tumour resection. AB - Psychological distress has a high prevalence in brain tumour patients, and understanding the emotional and personality changes that may follow neurosurgery is important for clinical management of these patients. We aimed to characterise these emotional and personality changes using subjective, observer-rated and clinical measures. We examined subjective changes in emotional experience and observer-rated changes to personality disturbances following neurosurgery for brain tumours (n=44), compared to a control group that had undergone spinal surgery (n=26). Participants completed the Hospital Anxiety and Depression Scale and a Subjective Emotional Change Questionnaire. Observers who knew the patients well also completed the Iowa Rating Scale of Personality Change. Compared to controls, patients with tumours reported significantly more changes to their subjective experience of emotions following neurosurgery, particularly anger, disgust and sadness. For the observer-ratings, tumour patients were described as having significant changes in the personality disturbances of irritability, impulsivity, moodiness, inflexibility, and being easily overwhelmed. Anxiety and depression were not significantly different between groups. Neurosurgical resection of a brain tumour is a major life event that changes patients' subjective experiences of different emotions, and leads to observer-rated changes in personality. In this study, these changes were not accompanied by increases in anxiety or depression. We conclude with a discussion of biological and psychosocial mechanisms that can impact emotional functioning and personality in patients with brain tumours. PMID- 26898574 TI - Heterogeneity induces rhythms of weakly coupled circadian neurons. AB - The main clock located in the suprachiasmatic nucleus (SCN) regulates circadian rhythms in mammals. The SCN is composed of approximately twenty thousand heterogeneous self-oscillating neurons, that have intrinsic periods varying from 22 h to 28 h. They are coupled through neurotransmitters and neuropeptides to form a network and output a uniform periodic rhythm. Previous studies found that the heterogeneity of the neurons leads to attenuation of the circadian rhythm with strong cellular coupling. In the present study, we investigate the heterogeneity of the neurons and of the network in the condition of constant darkness. Interestingly, we found that the heterogeneity of weakly coupled neurons enables them to oscillate and strengthen the circadian rhythm. In addition, we found that the period of the SCN network increases with the increase of the degree of heterogeneity. As the network heterogeneity does not change the dynamics of the rhythm, our study shows that the heterogeneity of the neurons is vitally important for rhythm generation in weakly coupled systems, such as the SCN, and it provides a new method to strengthen the circadian rhythm, as well as an alternative explanation for differences in free running periods between species in the absence of the daily cycle. PMID- 26898576 TI - Persistent pain as a non-motor symptom in corticobasal syndrome. AB - While a number of studies have investigated pain in Parkinson's disease, pain in corticobasal syndrome (CBS) remains understudied. This study evaluated the presence of persistent pain in CBS to determine whether it is a common non-motor symptom. We retrospectively evaluated the records of patients who were clinically diagnosed with CBS and re-examined or interviewed the patients for evaluation. There were 27 patients with clinically diagnosed CBS, of whom nine had persistent pain of unknown origin in addition to their disease. Seven patients had pain in their affected limbs, and the others had chest or neck pain. One patient's limb pain responded to levodopa treatment, but her parkinsonism responded poorly to the treatment. Pain could be a common non-motor symptom in CBS. Levodopa treatment should be considered because it might be beneficial in some patients. PMID- 26898577 TI - Preoperative angiotensin converting enzyme inhibitor usage in patients with chronic subdural hematoma: Associations with initial presentation and clinical outcome. AB - The aim of this study is to analyze the association of preoperative usage of angiotensin converting enzyme (ACE) inhibitors with the initial presentation and clinical outcome of patients with chronic subdural hematoma (cSDH). Patients treated for cSDH between 2009 and 2013 at our institution were included in this retrospective case-control study. Medical charts were reviewed retrospectively and data were analyzed using descriptive and inferential statistics. Out of 203 patients (58 females, mean age 73.2years), 53 (26%) patients were on ACE inhibitors before their presentation with cSDH. Median initial hematoma volume in individuals with ACE inhibitors (179.2+/-standard error of the mean [SEM] 13.0ml) was significantly higher compared to patients without ACE inhibitors (140.4+/-SEM 6.2ml; p=0.007). There was an increased probability of surgical reintervention in the ACE inhibitor group (12/53, 23% versus 19/153, 12%; p=0.079), especially in patients older than 80years (6/23, 26% versus 3/45, 7%; p=0.026). ACE inhibitors are associated with higher hematoma volume in patients with cSDH and with a higher frequency of recurrences requiring surgery (especially in the very old). We hypothesize that these effects are due to ACE inhibitor induced bradykinin elevation causing increased vascular permeability of the highly vascularized neomembranes in cSDH. PMID- 26898578 TI - Airplane stroke syndrome. AB - Only 37 cases of stroke during or soon after long-haul flights have been published to our knowledge. In this retrospective observational study, we searched the Royal Melbourne Hospital prospective stroke database and all discharge summaries from 1 September 2003 to 30 September 2014 for flight-related strokes, defined as patients presenting with stroke within 14days of air travel. We hypothesised that a patent foramen ovale (PFO) is an important, but not the only mechanism, of flight-related stroke. We describe the patient, stroke, and flight characteristics. Over the study period, 131 million passengers arrived at Melbourne airport. Our centre admitted 5727 stroke patients, of whom 42 (0.73%) had flight-related strokes. Flight-related stroke patients were younger (median age 65 versus 73, p<0.001), had similar stroke severity, and received intravenous thrombolysis more often than non-flight-related stroke patients. Seven patients had flight-related intracerebral haemorrhage. The aetiology of the ischaemic strokes was cardioembolic in 14/35 (40%), including seven patients with confirmed PFO, one with atrial septal defect, four with atrial fibrillation, one with endocarditis, and one with aortic arch atheroma. Paradoxical embolism was confirmed in six patients. Stroke related to air travel is a rare occurrence, less than one in a million. Although 20% of patients had a PFO, distribution of stroke aetiologies was diverse and was not limited to PFO and paradoxical embolism. PMID- 26898579 TI - Optical coherence tomography of the optic nerve head detects acute changes in intracranial pressure. AB - We aimed to determine if there are measurable objective changes in the optic nerve head (ONH) immediately after cerebrospinal fluid (CSF) drainage in a prospective case-series of five patients undergoing a clinically indicated lumbar puncture (LP) for diagnosis of idiopathic intracranial hypertension. A Cirrus high-definition optical coherence tomography machine (Carl Zeiss Meditec, Dublin, CA, USA) was used to acquire images in the lateral decubitus position. Optic disc cube and high-definition line raster scans centered on the ONH were obtained immediately before and after draining CSF, while the patient maintained the lateral decubitus position. Measured parameters included retinal nerve fiber layer (RNFL) thickness, peripapillary retinal pigment epithelium/Bruch's membrane (RPE/BM) angulation, transverse neural canal diameter (NCD) and the highest vertical point of the internal limiting membrane from the transverse diameter (papillary height). The mean (+/-standard deviation) opening and closing CSF pressures were 34.3+/-11.8 and 11.6+/-3.3cmH2O, respectively. Mean RNFL thickness (pre LP: 196+/-105MUm; post LP: 164+/-77MUm, p=0.1) and transverse NCD (pre LP: 1985+/-559MUm; post LP: 1590+/-228MUm, p=2.0) decreased in all subjects, but with non-significant trends. The RPE/BM angle (mean change: 5.8+/-2.0degrees, p=0.003) decreased in all subjects. A decrease in papillary height was seen in three of five subjects (mean: pre LP: 976+/-275MUm; post LP: 938+/-300MUm, p=0.9). Our results show a measurable, objective change in the ONH after acute lowering of the lumbar CSF pressure, suggesting a direct link between the lumbar subarachnoid space and ONH regions, and its potential as a non-invasive method for monitoring intracranial pressures. PMID- 26898580 TI - Pediatric familial neuromyelitis optica in two sisters with long term follow-up. AB - Neuromyelitis optica causes bilateral optic neuritis and longitudinal extensive transverse myelitis. Although usually sporadic, 3% of cases of neuromyelitis optica are familial. The interval over which attacks continue and the long term prognosis for pediatric-onset neuromyelitis optica are not well defined. We describe two patients with pediatric familial neuromyelitis optica with the longest clinical follow-up of a pediatric case reported in the literature to our knowledge. One woman developed blindness with bilateral eye involvement within a few weeks at age 3. This was followed by transverse myelitis with paraparesis at age 19 leading to diagnosis of neuromyelitis optica. Her serum anti-aquaporin 4 antibody was later found to be positive. She continued with sporadic myelitis related relapses but remained ambulant until age 40 when she had a more severe relapse. There was evidence of longitudinal extensive T2 hyperintensity in the thoracic spinal cord. Her sister also developed blindness at age 3.5 followed by myelitis 1year later with multiple relapses of gait impairment until her death from pneumonia at age 21. These patients represent the rare occurrence of neuromyelitis optica in children within the same family and show that this disease can have prolonged periods of remission but a continued tendency to relapse, supporting the need for lifelong immunosuppression. PMID- 26898581 TI - Side predilections of offending arteries in hemifacial spasm. AB - The side predilections of various offending arteries in hemifacial spasm (HFS) have not been well studied. The relationship between clinical and radiological features of HFS and offending arteries were investigated in the present study. A retrospective analysis of 370 patients who underwent microvascular decompression for HFS was performed. The patients were divided into four groups based on the offending arteries, namely anterior inferior cerebellar artery (AICA), posterior inferior cerebellar artery (PICA), vertebral artery, and multiple offending arteries. Affected side, age at onset, presence of hypertension, and sigmoid sinus area and dominance were compared between groups. The mean age of patients with a left HFS was significantly greater than that of patients with a right HFS (P=0.009). The AICA affected primarily the right side and PICA and multiple offending arteries the left side (P<0.001). Side of sigmoid sinus dominance was significantly different among groups (P<0.001). The offending arteries in HFS may be related to these differences. AICA was associated with right-sided symptoms, younger age at onset, and presence of left dominant sigmoid sinus, while PICA was associated with left-sided symptoms, older age at onset, and smaller right sigmoid sinus area. PMID- 26898582 TI - Clinical outcomes after decompressive laminectomy for symptomatic ossification of ligamentum flavum at the thoracic spine. AB - Ossification of the ligamentum flavum (OLF) is a rare disease that causes acquired thoracic spinal canal stenosis and thoracic myelopathy. The aim of this study was to investigate clinical outcomes of symptomatic thoracic OLF treated using posterior decompressive laminectomy. We retrospectively analyzed the medical records of 22 patients who underwent posterior decompressive laminectomy for symptomatic thoracic OLF. The surgical results were evaluated using the modified Japanese Orthopaedic Association (JOA) scoring system and Hirabayashi recovery rate. The intensity of pain was evaluated using a visual analog scale (VAS). The mean duration of follow-up was 35.6months. The mean JOA score was significantly improved at final follow-up (9.18+/-standard deviation of 1.53 points [range, 6-11 points]) compared with before surgery (5.64+/-2.04 points [range, 3-9 points]) (P<0.001). The mean Hirabayashi recovery rate was 65.49% (range, 20-100%). Recovery outcomes were excellent in nine patients, good in eight patients, fair in four patients and unchanged in one patient. No patient was classified as deteriorated. The VAS scores were 2.82+/-3.08 before surgery and 0.59+/-1.05 at final follow-up (P=0.001). Surgical complications, which resolved after appropriate and prompt treatment, included dural tear in five patients, cerebrospinal fluid leakage in one patient, immediate postoperative neurologic deterioration in one patient, epidural hematoma in one patient, and wound infection in one patient. Our findings suggest that posterior decompressive laminectomy is an effective treatment for symptomatic thoracic OLF and provides satisfactory clinical improvement, but surgery for thoracic OLF is associated with a relatively high incidence of complications. PMID- 26898584 TI - The Ancient Greek discovery of the nervous system: Alcmaeon, Praxagoras and Herophilus. AB - The aim of this historical overview is to show that the theories of Alcmaeon of Croton formed an important part of a developing conception of the brain and the nervous system. The vital contributions of Praxagoras of Kos, who suggested the existence of what we now call "neurons", and Herophilus of Chalcedon, who distinguished between sensory and motor nerves and demonstrated the existence of the nervous system by dissection, also established the foundation principles of neuroscience, but their importance is sometimes forgotten. We trace the discovery of the nervous system through an investigation of these three thinkers. Combining astounding philosophical concepts with sharp observation, they conceived and demonstrated the existence of a nervous system by the third century BCE. This discovery is central not only to neuroscience, but also to all of medicine and to our concept of the human organism: it articulated the connection between the mind, the brain, and the body. PMID- 26898583 TI - Comparison of outcomes between patients with idiopathic normal pressure hydrocephalus who received a primary versus a salvage shunt. AB - Placement of a ventriculoperitoneal (VP) shunt is the treatment of choice for communicating hydrocephalus; however, the extent to which VP shunting is able to relieve symptoms in patients who had previously been treated with cerebrospinal fluid diverting therapy at an outside institution remains unclear. A retrospective review of patients with idiopathic normal pressure hydrocephalus treated with VP shunts at a single institution between 1993 and 2013 was conducted. Patients were classified as having received a primary VP shunt if they had not been previously treated with a VP shunt, ventriculoatrial shunt, lumboperitoneal shunt, or endoscopic third ventriculostomy. Patients were classified as having received a salvage VP shunt if they had been previously treated by one of these four modalities at an outside institution prior to their presentation to our institution. There were 357 patients who received a primary shunt and 33 patients who received a salvage shunt. Patients who had a salvage shunt placed had significantly higher odds of requiring a future revision (54% versus 41%; odds ratio=2.85; 95% confidence interval [CI]: 1.24-6.57; p=0.014). Patients who received a salvage shunt had statistically significantly lower rates of gait improvement at 6months in comparison to patients who received a primary shunt (relative risk=0.35; 95% CI: 0.14-0.87; p=0.025). Despite these findings, there was no significant difference at last follow-up in improvement in gait, continence, and cognition, indicating that outcomes for patients requiring a salvage shunt were comparable to patients receiving a primary shunt. PMID- 26898585 TI - Editorial: The biodiversity of trematodes of fishes. PMID- 26898586 TI - Knowledge of marine fish trematodes of Atlantic and Eastern Pacific Oceans. AB - A brief summary of the early history of the study of Atlantic Ocean marine fish digeneans is followed by a discussion of the occurrence and distribution of these worms in the Atlantic Ocean and adjacent Eastern Pacific Ocean, using the Provinces of the 'Marine Ecoregions' delimited by Spalding et al. (Bioscience 57:573-583, 2007). The discussion is based on a database of 9,880 records of 1,274 species in 430 genera and 45 families. 8,633 of these records are from the Atlantic Ocean, including 1,125 species in 384 genera and 45 families. About 1,000 species are endemic to the Atlantic Ocean Basin. The most species-rich families in the Atlantic Ocean are the Opecoelidae Ozaki, 1925, Hemiuridae Looss, 1899 and Bucephalidae Poche, 1907, and the most wide-spread the Opecoelidae, Hemiuridae, Acanthocolpidae Luhe, 1906, Lepocreadiidae Odhner, 1905 and Lecithasteridae Odhner, 1905. A total of 109 species are shared by the Atlantic Ocean and the Eastern Pacific, made up of cosmopolitan, circum-boreal, trans Panama Isthmus and Magellanic species. The lack of genetic evaluation of identifications is emphasised and the scope for much more work is stressed. PMID- 26898587 TI - Trematodes of fishes of the Indo-west Pacific: told and untold richness. AB - The Indo-west Pacific is a marine bioregion stretching from the east coast of Africa to Hawaii, French Polynesia and Easter Island. An assessment of the literature from the region found reports of 2,582 trematode species infecting 1,485 fish species. Reports are concentrated in larger fishes, undoubtedly reflecting the tendency for larger hosts to be infected by more species of parasites as well as a collecting bias. Many hundreds of fish species, including many from families known to be rich in trematodes, have yet to be reported as hosts. Despite some areas (the Great Barrier Reef, Hawaii and the waters off China, India and Japan) receiving sustained attention, none can be considered to be comprehensively known. Several regions, most importantly in East Africa, French Polynesia and the Coral Triangle, are especially poorly known. The fauna of the Indo-west Pacific has been reported so unevenly that we consider it impossible to predict the true trematode richness for the region. We conclude that the greatest gap in our understanding is of the geographical distribution of species in the Indo-west Pacific. This is highlighted by the fact that 87% of trematodes in the region have been reported no more than five times. The reliable recognition of species is a major problem in this field; molecular approaches offer prospects for resolution of species identification but have been little adopted to date. PMID- 26898588 TI - The Mediterranean: high discovery rates for a well-studied trematode fauna. AB - Our knowledge of trematode diversity in Mediterranean Sea fishes is based on many contributions since the early 1800s (e.g. by Rudolphi, Stossich, Looss, Bartoli, Bray and Gibson). We have updated data from the Natural History Museum Host Parasite Database and listed 302 digenean trematode species allocated to 146 genera in 29 families from 192 fish species (27% of the known fish-fauna) belonging to 76 families. The most diverse (with 31-41 species) digenean families (Opecoelidae Ozaki, 1925, Didymozoidae Monticelli, 1888 and Hemiuridae Looss, 1899) represent more than a third of the total richness (36% of species) and have been most frequently recorded (43% of the records). The overall mean number of species per host is close to recent global estimates for digenean richness in teleosts (1.57 vs 2.04, respectively), indicating a high diversity in the Mediterranean. The most diverse host families are also the best studied. However, three speciose host families (Rajidae de Blainville, Gobiidae Cuvier and Myctophidae Gill) appear under-studied and no digenean reports exist for 94 of 169 fish families present in the Mediterranean. Thus, although Mediterranean fishes appear well studied, further efforts are needed. Nevertheless, the descriptions of a large number of new taxa since 2000 indicate that focused efforts have resulted in a high discovery rate (2.4 species per year). Many of these new (often cryptic) taxa are the result of combined morphological and molecular methods, which promise more reliable estimates of digenean diversity in this region. We provide host-parasite lists for 192 species of fish in the Mediterranean comprising 890 host-parasite associations. PMID- 26898589 TI - Trematode diversity in freshwater fishes of the Globe I: 'Old World'. AB - In this paper, we review, continent by continent, the trematode fauna of freshwater fishes of the 'Old World', a vast area consisting of the Palaearctic, Ethiopian, Oriental and Australasian zoogeographical regions. Knowledge of this fauna is highly uneven and clearly incomplete for almost all regions, sometimes dramatically so. Although the biggest problem remains the completion of the 'first pass' of alpha taxonomy, there are in addition great problems relating to biogeography and elucidation of life-cycles. For the latter, molecular data, i.e. matching DNA sequences of larval stages and corresponding adults, may represent a powerful tool that should be used in future studies. Another challenging problem represents the existence of cryptic species and, in particular, considerable decrease of experts in taxonomy and life-cycles of trematodes. PMID- 26898590 TI - Trematode diversity in freshwater fishes of the Globe II: 'New World'. AB - We provide a summary overview of the diversity of trematode parasites in freshwater fishes of the 'New World', i.e. the Americas, with emphasis on adult forms. The trematode fauna of three regions, South America, Middle America, and USA and Canada (North America north of Mexico), are considered separately. In total, 462 trematode species have been reported as adults from the Americas. The proportion of host species examined for parasites varies widely across the Americas, from a high of 45% in the Mexican region of Middle America to less than 5% in South America. North and South America share no adult species, and one exclusively freshwater genus, Creptotrema Travassos, Artigas & Pereira, 1928 in the Allocreadiidae Looss, 1902 is the most widely distributed. Metacercariae of strigeiforms maturing in fish-eating birds (e.g. species of the Diplostomidae Poirier, 1886) are common and widely distributed. The review also highlights the paucity of known life-cycles. The foreseeable future of diversity studies belongs to integrative approaches and the application of molecular ecological methods. While opportunistic sampling will remain important in describing and cataloguing the trematode fauna, a better understanding of trematode diversity and biology will also depend on strategic sampling throughout the Americas. PMID- 26898591 TI - Biodiversity of trematodes in their intermediate mollusc and fish hosts in the freshwater ecosystems of Europe. AB - We analysed two novel databases containing 2,380 and 8,202 host-parasite-locality records for trematode parasites of molluscs and fishes, respectively, to assess the biodiversity of trematodes in their intermediate mollusc and fish hosts in the freshwater environment in Europe. The "mollusc" dataset covers large numbers of pulmonate (29 spp.), "prosobranch" (15 spp.) and bivalve (11 spp.) molluscs acting as first intermediate hosts for 171 trematode species of 89 genera and 35 families. Of these, 23 and 40 species utilise freshwater fishes as definitive and second intermediate hosts, respectively. The most frequently recorded families are the Echinostomatidae Looss, 1899, Diplostomidae Poirier, 1886 and Schistosomatidae Stilles & Hassal, 1898, and the most frequently recorded species are Diplostomum spathaceum (Rudolphi, 1819), D. pseudospathaceum Niewiadomska, 1984 and Echinoparyphium recurvatum (von Linstow, 1873). Four snail species harbour extremely rich trematode faunas: Lymnaea stagnalis (L.) (41 spp.); Planorbis planorbis (L.) (39 spp.); Radix peregra (O.F. Muller) (33 spp.); and R. ovata (Draparnaud) (31 spp.). The "fish" dataset covers 99 fish species of 63 genera and 19 families acting as second intermediate hosts for 66 species of 33 genera and nine families. The most frequently recorded families are the Diplostomidae Poirier, 1886, Strigeidae Railliet, 1919 and Bucephalidae Poche, 1907, and the most frequently recorded species are Diplostomum spathaceum (Rudolphi, 1819), Tylodelphys clavata (von Nordmann, 1832) and Posthodiplostomum cuticola (von Nordmann, 1832). Four cyprinid fishes exhibit the highest species richness of larval trematodes: Rutilus rutilus (L.) (41 spp.); Abramis brama (L.) (34 spp.); Blicca bjoerkna (L.) (33 spp.); and Scardinius erythrophthalmus (L.) (33 spp.). Larval stages of 50 species reported in fish are also reported in freshwater molluscs, thus indicating a relatively good knowledge of the life cycles of fish trematodes in Europe. We provide host-parasite lists for 55 species of molluscs with a European distribution comprising 413 host-parasite associations. PMID- 26898593 TI - Effects of indigo carmine intravenous injection on noninvasive and continuous total hemoglobin measurement with using the Revision L sensor. AB - The effects of intravenous injection of indigo carmine on noninvasive and continuous total hemoglobin (SpHb) measurement were retrospectively evaluated with the Revision L sensor. The subjects were 18 patients who underwent elective gynecologic surgery under general anesthesia. During surgery, 5 mL of 0.4 % indigo carmine was injected intravenously, and changes in SpHb concentrations between before and after the injection were evaluated. The mean age was 52.4 +/- 12.8 years. Before injection, the median SpHb level was 10.1 (range, 6.8-13.4) g/dL. The results demonstrated no change in SpHb concentration between before and after indigo carmine injection as detected by the Revision L sensor. SpHb measurements as determined with the Revision L sensor were not affected, even after the intravenous injection of indigo carmine. PMID- 26898592 TI - Molecular approaches to trematode systematics: 'best practice' and implications for future study. AB - To date, morphological analysis has been the cornerstone to trematode systematics. However, since the late-1980s we have seen an increased integration of genetic data to overcome problems encountered when morphological data are considered in isolation. Here, we provide advice regarding the 'best molecular practice' for trematode taxonomy and systematic studies, in an attempt to help unify the field and provide a solid foundation to underpin future work. Emphasis is placed on defining the study goals and recommendations are made regarding sample preservation, extraction methods, and the submission of molecular vouchers. We advocate generating sequence data from all parasite species/host species/geographic location combinations and stress the importance of selecting two independently evolving loci (one ribosomal and one mitochondrial marker). We recommend that loci should be chosen to provide genetic variation suitable to address the question at hand and for which sufficient 'useful' comparative sequence data already exist. Quality control of the molecular data via using proof-reading Taq polymerase, sequencing PCR amplicons using both forward and reverse primers, ensuring that a minimum of 85% overlap exists when constructing consensus sequences, and checking electropherograms by eye is stressed. We advise that all genetic results are best interpreted using a holistic biological approach, which considers morphology, host identity, collection locality, and ecology. Finally, we consider what advances next-generation sequencing holds for trematode taxonomy and systematics. PMID- 26898594 TI - Subacute progressive disseminated histoplasmosis in immunocompetent patient. PMID- 26898595 TI - Treatment outcomes and clinical relevance of the Follicular Lymphoma International Prognostic Index in Korean follicular lymphoma patients treated with chemotherapy. AB - BACKGROUND/AIMS: The Follicular Lymphoma International Prognostic Index (FLIPI) and FLIPI2 are well-known prognostic models for patients with follicular lymphoma (FL). However, their prognostic relevance has not been examined before in Korean patients with FL. METHODS: We reviewed clinical and laboratory information from our database of patients between 1995 and 2012. In total, 125 patients were stratified in three categories according to FLIPI or FLIPI2 scores: low-, intermediate-, and high-risk groups. We compared FLIPI and FLIPI2 in terms of progression-free survival (PFS) and overall survival (OS). RESULTS: Among the 125 patients, the prognostic value of FLIPI and FLIPI2 was evaluated in 73 patients who fulfilled the criteria of both prognostic models. Risk stratification by FLIPI and FLIPI2 showed significant differences in unfavorable parameters among each risk group, particularly between low- and intermediate-risk groups. The high risk group b was significantly associated with poor PFS on both FLIPI and FLIPI2 (p < 0.05). However, the OS was significantly different only in the risk groups determined by FLIPI2 (p = 0.042). In a subgroup analysis of patients who received rituximab-containing chemotherapy, the risk stratification of both prognostic models showed a significant impact on PFS, especially in the low-risk group. CONCLUSIONS: FLIPI and FLIPI2 are appropriate prognostic models in Korean FL patients, especially for discriminating low-risk patients from intermediate- and high-risk groups. PMID- 26898596 TI - The impact of blood flow rate during hemodialysis on all-cause mortality. AB - BACKGROUND/AIMS: Inadequacy of dialysis is associated with morbidity and mortality in chronic hemodialysis (HD) patients. Blood flow rate (BFR) during HD is one of the important determinants of increasing dialysis dose. However, the optimal BFR is unclear. In this study, we investigated the impact of the BFR on all-cause mortality in chronic HD patients. METHODS: Prevalent HD patients were selected from Clinical Research Center registry for end-stage renal disease cohort in Korea. We categorized patients into two groups by BFR < 250 and >= 250 mL/min according to the median value of BFR 250 mL/min in this study. The primary outcome was all-cause mortality. RESULTS: A total of 1,129 prevalent HD patients were included. The number of patients in the BFR < 250 mL/min was 271 (24%) and in the BFR >= 250 mL/min was 858 (76%). The median follow-up period was 30 months. Kaplan-Meier analysis showed that the mortality rate was significantly higher in patients with BFR < 250 mL/min than those with BFR >= 250 mL/min (p = 0.042, log-rank). In the multivariate Cox regression analyses, patients with BFR < 250 mL/min had higher all-cause mortality than those with BFR >= 250 mL/min (hazard ratio, 1.66; 95% confidence interval, 1.00 to 2.73; p = 0.048). CONCLUSIONS: Our data showed that BFR < 250 mL/min during HD was associated with higher all-cause mortality in chronic HD patients. PMID- 26898597 TI - Endoscopic submucosal dissection of gastric subepithelial tumors: a systematic review and meta-analysis. AB - BACKGROUND/AIMS: To evaluate the therapeutic outcomes of the endoscopic submucosal dissection (ESD) technique for the treatment of gastric subepithelial tumors (SETs). METHODS: A systematic literature review was conducted using the core databases. Data on the complete resection rates and the procedure-related perforation rates were extracted and analyzed. A random effects model was then applied for this meta-analysis. RESULTS: In all, 288 patients with 290 SETs were enrolled from nine studies (44 SETs originated from the submucosal layer; 246 SETs originated from the muscularis propria layer). The mean diameter of the lesions ranged from 17.99 to 38 mm. Overall, the pooled complete resection rate was estimated to be 86.2% (95% confidence interval [CI], 78.9 to 91.3). If the analysis was limited to the lesions that originated from the submucosal layer, the pooled complete resection rate was 91.4% (95% CI, 77.9 to 97). If the analysis was limited to the lesions that originated from the muscularis propria, the pooled complete resection rate was 84.4% (95% CI, 78.7 to 88.8). The pooled procedure-related gastric perforation rate was 13% (95% CI, 9.4 to 17.6). Sensitivity analyses showed consistent results. Finally, publication bias was not detected. CONCLUSIONS: ESD, including endoscopic muscularis dissection, is a technically feasible procedure for the treatment of SETs. However, selection bias is suspected from the enrolled studies. For the development of a proper indication of ESD for SETs, further studies are needed. PMID- 26898598 TI - Association between blood glucose level derived using the oral glucose tolerance test and glycated hemoglobin level. AB - BACKGROUND/AIMS: Glycated hemoglobin (HbA1c) is widely used as a marker of glycemic control. Translation of the HbA1c level to an average blood glucose level is useful because the latter figure is easily understood by patients. We studied the association between blood glucose levels revealed by the oral glucose tolerance test (OGTT) and HbA1c levels in a Korean population. METHODS: A total of 1,000 subjects aged 30 to 64 years from the Cardiovascular and Metabolic Diseases Etiology Research Center cohort were included. Fasting glucose levels, post-load glucose levels at 30, 60, and 120 minutes into the OGTT, and HbA1c levels were measured. RESULTS: Linear regression of HbA1c with mean blood glucose levels derived using the OGTT revealed a significant correlation between these measures (predicted mean glucose [mg/dL] = 49.4 * HbA1c [%] - 149.6; R (2) = 0.54, p < 0.001). Our linear regression equation was quite different from that of the Alc-Derived Average Glucose (ADAG) study and Diabetes Control and Complications Trial (DCCT) cohort. CONCLUSIONS: Discrepancies between our results and those of the ADAG study and DCCT cohort may be attributable to differences in the test methods used and the extent of insulin secretion. More studies are needed to evaluate the association between HbA1c and self monitoring blood glucose levels. PMID- 26898599 TI - Formulating treatment recommendation as a logical consequence of the diagnosis in post-surgical oncological visits. AB - OBJECTIVE: the article analyzes how a doctor delivers diagnoses and recommends treatment in a set of post-surgical oncological visits. The pattern of activities are explored in two different cases: when all diagnostic information is available, and when information is still missing. METHODS: The data consist of 12 video-recorded visits of breast cancer patients to a senior oncologist. Conversation analysis is employed to analyze sequences in which the delivery of diagnosis and treatment recommendation unfold. RESULTS: The oncologist formulates the treatment recommendation as a logical consequence deriving from the available diagnostic information. In cases when definitive diagnostic information on the cancer type is missing, the oncologist opts to anticipate hypothetical diagnostic scenarios, and to draw the therapeutic alternatives as logical outcomes envisionable from each of the different scenarios. CONCLUSION: The communicative practice appears functional to encourage the patients' acceptance of a single treatment option rather than present the patients to and involve them in deliberating over multiple available treatment alternatives. PRACTICE IMPLICATIONS: Rather than a normative adoption of existing protocols of communication in cancer care, a better understanding of communication practices in use can help practitioners to reflect upon and make intentional choices about different arrangements for the patient's participation. PMID- 26898602 TI - Target effect on the kinematics of Taekwondo Roundhouse Kick - is the presence of a physical target a stimulus, influencing muscle-power generation? AB - Taekwondo is famous for its powerful kicking techniques and the roundhouse kick is the most frequently used one. In earlier literature, the influence of a physical target (exiting or not) on kicking power generation has not been given much attention. Therefore, the aim of this study was to investigate the kinematics of roundhouse kick execution and its factors related to power generation. 6 ITF taekwondo practitioners voluntarily participated in this study. They were asked to perform kicks with and without a physical target. The first kick aimed at breaking a board while the second one was a kick into the air. A Smart-D motion capture system (BTS S.p.A., Italy) was used to quantitatively determine their kinematic characteristics during each kick. The main findings showed that kicks aiming at a breaking board were significantly slower than kicks without a physical target (maximal kick-foot velocities were 10.61 +/- 0.86 m/s and 14.61 +/- 0.67 m/s, respectively, p < 0.01), but the kicking time of the former was shorter (0.58 +/- 0.01 s and 0.67 +/- 0.01, respectively, p < 0.01). The results suggest that a physical target will negatively influence the kick foot velocity, which is not necessarily a disadvantage for creating a high quality kick. Possible motor control mechanisms are discussed for the phenomenon. The study made it clear: trainings with and without physical targets would develop different motor control patterns. More studies are needed for identifying the effectiveness of different controls and efficiencies of their training. PMID- 26898600 TI - The impact of a self-management patient education program for patients with chronic heart failure undergoing inpatient cardiac rehabilitation. AB - OBJECTIVE: To evaluate a patient-centred self-management educational group program for patients with chronic systolic heart failure as compared to usual care education during inpatient cardiac rehabilitation. METHODS: A multicentre cluster randomized controlled trial of 475 patients was conducted. In the intervention condition, patients received the new self-management educational group program whereas in the control condition, patients received a short lecture based educational program (usual care). The primary outcome was patients' self reported self-management competence. Secondary outcomes included self-management health behaviour, health-related quality of life, and treatment satisfaction. Patients completed self-reported outcome measures at admission, discharge, and after 6 and 12 months. RESULTS: There was a significant small between-group intervention effect on certain dimension of patients' self-management competence (self-monitoring and insight) in short term (p<0.05). Furthermore, significant small effects were observed for treatment satisfaction at discharge as well as symptom monitoring after 6 months (p<0.05) and by trend on symptom monitoring and physical activity after 12 months. CONCLUSIONS: The patient-centred self management program might be more effective in certain self-management outcomes than a usual care education in both short-term and long-term periods. PRACTICE IMPLICATIONS: Therefore, such programs may be considered for dissemination within cardiac rehabilitation. PMID- 26898603 TI - Insertion and C-C coupling processes in reactions of the unsaturated hydride [W2Cp2(H)(MU-PCy2)(CO)2] with alkynes. AB - The title compound reacted with p-tolylacetylene at room temperature to give the 32-electron sigma:pi-bound alkenyl complexes trans-[W2Cp2{MU-kappa:eta(2)-C(p tol)CH2}(MU-PCy2)(CO)2] and trans-[W2Cp2{MU-kappa:eta(2)-CHCH(p-tol)}(MU PCy2)(CO)2], with the former complex fully rearranging into the latter one after 1 h at 363 K. Both compounds exist in solution as an isomeric equilibrium mixture (rapid on the NMR timescale) involving the alternate pi-coordination of the alkenyl ligand to each of the tungsten atoms. In the presence of CO or certain solvents (THF or CH2Cl2) the alpha-substituted alkenyl complex was transformed instead into the cis-dicarbonyl isomer cis-[W2Cp2{MU-kappa:eta(2)-C(p-tol)CH2}(MU PCy2)(CO)2] (W-W = 2.7273(8) A). In contrast, the beta-substituted alkenyl complex reacted with CO to give the saturated tricarbonyl [W2Cp2{MU-kappa:eta(2) CHCH(p-tol)}(MU-PCy2)(CO)3], and with excess alkyne (under moderate heating) to yield the alkyne/alkenyl complex [W2Cp2{MU-kappa:eta(2)-CHCH(p-tol)}(MU PCy2){eta(2)-CHC(p-tol)}(CO)], with both products also displaying a cisoid disposition of the Cp ligands. In contrast, reactions of the title hydride with tert-butylacetylene were significantly slower and led to very air-sensitive compounds, the only isolable product from these reactions being the oxo alkenyl complex trans-[W2Cp2{MU-kappa:eta(2)-CHCH((t)Bu)}(O)(MU-PCy2)(CO)]. The title hydride reacted with methyl propiolate at room temperature to give selectively the alpha-substituted alkenyl complex cis-[W2Cp2{MU-kappa:eta(2)-C(CO2Me)CH2}(MU PCy2)(CO)2], but yielded instead the dienyl complex [W2Cp2{MU-kappa(2):eta(3) CH(CO2Me)CHC(CO2Me)CH}(MU-PCy2)(CO)2] (W-W = 2.944(1) A) when the reaction was carried out at high temperature (393 K), with the latter generated from an alkenyl/alkyne C-C coupling process. The title hydride also reacted with dimethyl acetylenedicarboxylate, to give three products mainly depending on the reaction temperature; at moderate temperature (343 K) this reaction led exclusively to the saturated alkenyl complex trans-[W2Cp2{MU-kappaC,kappaO:eta(2) C(CO2Me)CH(CO2Me)}(MU-PCy2)(CO)2] (W-W = 2.9329(8) A), in which the sigma:pi bound alkenyl ligand is additionally coordinated through the oxygen atom of the carboxylate group so as to render a O,C:C,C' five-electron coordination mode. At 273 K this reaction led instead to a mixture of the unsaturated alkenyl cis [W2Cp2{MU-kappa:eta(2)-C(CO2Me)[double bond, length as m-dash]CH(CO2Me)}(MU PCy2)(CO)2] and the dienyl complex [W2Cp2{MU-kappaC,kappaO:eta(2)-C(CO2Me)[double bond, length as m-dash]C(CO2Me)C(CO2Me)[double bond, length as m dash]CH(CO2Me)}(MU-PCy2)(CO)2] (W-W = 3.0273(6) A). PMID- 26898604 TI - Maternal mental health symptoms are positively related to emotional and restrained eating attitudes in a statewide sample of mothers participating in a supplemental nutrition program for women, infants and young children. AB - Postpartum, low-income mothers are at risk for mental health symptoms and obesity, and disordered eating attitudes may be associated with both mental health and obesity in this vulnerable population. The study objective is to determine whether higher levels of mental health symptoms are associated with increased odds of emotional and restrained eating attitudes in this sample of Special Supplemental Nutrition Program for Women, Infants and Children (WIC) participants. Data on 711 mothers of infants <13 months from a statewide sample of Maryland WIC participants were collected via telephone survey. Maternal mental health symptoms were measured on continuous scales for depression (PRIME-MD), stress (Perceived Stress Scale) and anxiety (Spielberger State-Trait Anxiety Inventory). Emotional and restrained eating attitudes were measured with questions adapted from the Dutch Eating Behavior Questionnaire. Multivariate logistic regression analysis was used. Obesity [body mass index (BMI) >= 30] was explored as a moderating variable. Mothers reporting higher levels of depression symptoms [odds ratio (OR) = 3.93, 95%CI: 2.71-5.69], anxiety symptoms (OR = 1.96, 95%CI: 1.47-2.65), stress symptoms (OR = 2.09, 95%CI: 1.67-2.61) and high overall mental health symptomatology (OR = 3.51, 95%CI: 2.43-5.3) had increased odds of emotional eating attitudes. There were significant associations between symptoms of depression (OR = 1.59, 95% CI: 1.12-2.25) and increased odds of restrained eating attitudes. Obesity did not moderate the association. Mothers with mental health symptoms are at risk for disordered eating attitudes, which may increase risk of poor diet. These findings underscore the need for greater focus on addressing maternal mental health status and eating attitudes in the postpartum period. PMID- 26898605 TI - Serum amylase and C-reactive protein in risk stratification of pancreas-specific complications after pancreaticoduodenectomy. AB - BACKGROUND: Pancreas-specific complications (PSCs), comprising postoperative pancreatic fistula, haemorrhage and intra-abdominal collections, are drivers of morbidity and mortality after pancreaticoduodenectomy (PD). A serum amylase concentration of 130 units/l or more on postoperative day (POD) 0 has been shown to be an objective surrogate of pancreatic texture, a determinant of PSCs. This study evaluated serial measurements of C-reactive protein (CRP) to refine PSC risk stratification. METHODS: Consecutive patients undergoing PD between 2008 and 2014, with vascular resection if required and without preoperative chemoradiotherapy, had serum investigations from the day before operation until discharge. Receiver operating characteristic (ROC) curve analysis was used to identify a threshold value of serum CRP with clinically relevant PSCs for up to 30 days after discharge as outcome measure. RESULTS: Of 230 patients, 95 (41.3 per cent) experienced a clinically relevant PSC. A serum CRP level of 180 mg/l or higher on POD 2 was associated with PSCs, prolonged critical care stay and relaparotomy (all P < 0.050). Patients with a serum amylase concentration of 130 units/l or more on POD 0 who developed a serum CRP level of at least 180 mg/l on POD 2 had a higher incidence of morbidity. Patients were stratified into high-, intermediate- and low-risk groups using these markers. The low-risk category was associated with a negative predictive value of 86.5 per cent for development of clinically relevant PSCs. There were no deaths among 52 patients in the low-risk group, but seven deaths among 79 (9 per cent) in the high-risk group. CONCLUSION: A serum amylase level below 130 units/l on POD 0 combined with a serum CRP level under 180 mg/l on POD 2 constitutes a low-risk profile following PD, and may help identify patients suitable for early discharge. PMID- 26898606 TI - Cellular microenvironment modulates the galvanotaxis of brain tumor initiating cells. AB - Galvanotaxis is a complex process that represents the collective outcome of various contributing mechanisms, including asymmetric ion influxes, preferential activation of voltage-gated channels, and electrophoretic redistribution of membrane components. While a large number of studies have focused on various up- and downstream signaling pathways, little is known about how the surrounding microenvironment may interact and contribute to the directional response. Using a customized galvanotaxis chip capable of carrying out experiments in both two- and three-dimensional microenvironments, we show that cell-extracellular matrix (ECM) interactions modulate the galvanotaxis of brain tumor initiating cells (BTICs). Five different BTICs across three different glioblastoma subtypes were examined and shown to all migrate toward the anode in the presence of a direct-current electric field (dcEF) when cultured on a poly-L-ornithine/laminin coated surface, while the fetal-derived neural progenitor cells (fNPCs) migrated toward the cathode. Interestingly, when embedded in a 3D ECM composed of hyaluronic acid and collagen, BTICs exhibited opposite directional response and migrated toward the cathode. Pharmacological inhibition against a panel of key molecules involved in galvanotaxis further revealed the mechanistic differences between 2- and 3D galvanotaxis in BTICs. Both myosin II and phosphoinositide 3-kinase (PI3K) were found to hold strikingly different roles in different microenvironments. PMID- 26898607 TI - A multicenter phase II study of sorafenib in combination with erlotinib in patients with advanced non-small cell lung cancer (KCSG-0806). AB - OBJECTIVES: Sorafenib and erlotinib are potent, orally administered receptor tyrosine kinase inhibitors with antiproliferative and antiangiogenic activities. Given their synergistic activity in combination, we conducted a phase II study to determine the clinical activity of sorafenib in combination with erlotinib in patients with advanced non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Patients with advanced NSCLC who have received one or two prior chemotherapy regimens for metastatic disease, ECOG 0-2, and adequate organ function were eligible. Patients received 400mg twice daily sorafenib and 150 mg daily erlotinib in 28-day cycles. Epidermal growth factor receptor mutation and its downstream pathways were analyzed from available tumor samples. Changes in plasma cytokine and angiogenic factors were correlated with clinical outcomes. RESULTS: A total of 46 patients were enrolled. Twenty patients (43%) were never smokers and 35 patients (75%) had adenocarcinoma histology. The overall response rate was 30.4%. Response to sorafenib/erlotinib was observed more commonly in patients with EGFR mutation than in those with EGFR wild type (WT) or EGFR unknown tumors (62.5% vs. 6.7% vs. 34.8%; P=0.013). Likewise, DCR was higher among patients with EGFR mutation than in those with EGFR WT or EGFR unknown tumors (87.5% vs. 46.7% vs. 60.9%; P=0.161). The most frequent adverse events (AEs) of all grades were hand-foot skin reaction (67.4%) followed by acneiform rash (58.7%). CONCLUSION: Sorafenib combined with erlotinib is well-tolerated with manageable toxicity and appears to be effective against advanced NSCLC with one or two prior line of systemic treatment (NCT00801385). PMID- 26898608 TI - PD-L1 on peripheral blood T lymphocytes is prognostic in patients with non-small cell lung cancer (NSCLC) treated with EGFR inhibitors. AB - OBJECTIVES: The immune effects of EGFR tyrosine kinase inhibitors (EGFR-TKIs) are poorly understood. Identifying immune biomarkers could guide patient selection and optimisation of EGFR-TKI-immunotherapy combinations. MATERIALS AND METHODS: 33 patients with NSCLC treated with an EGFR-TKI were prospectively enrolled. Peripheral blood mononuclear cells were collected pre-treatment, and after 1, 3 and 8 weeks. Flow cytometry was used to identify immune cell subsets, including PD-1 and PD-L1 expressing T cells. Immune parameters were correlated with clinical outcomes. RESULTS: Compared to healthy donors (n=10), patients had higher pre-treatment proportions of proliferating and PD-L1(+)CD3(+) T cells (p<0.001). Compared to patients with an EGFR mutation (n=12), patients without a known mutation (n=21) had higher proportions of proliferating CD4(+) and PD L1(+)CD3(+) T cells (p=0.03). There was a significant increase in PD-L1(+) T cells after 1 week of EGFR-TKI in patients whose disease progressed compared to non-progressors. Patients with higher PD-L1(+)CD3(+) T cells at 1-week were more likely to progress (OR 30.3, p<0.01) and had shorter PFS (1.6 vs. 8.8m; p<0.01) and OS (3.8 vs 23.2m; p<0.001) than those with fewer PD-L1(+)CD3(+) T cells. On multivariate analysis, high PD-L1(+)CD3(+) T cells was the only independent predictor for PFS (HR 3.7, p=0.01), while for OS independent predictors were high PD-L1(+)CD3(+) T cells (HR 6.5, p<0.01) and EGFR-negative status (HR 3.3, p=0.04). CONCLUSIONS: There was a significant correlation between PD-L1 expression on peripheral T cells and clinical outcomes in EGFR-TKI-treated NSCLC. This warrants further validation as a blood-based biomarker that may identify candidates for PD-1 inhibitors or immunotherapy-EGFR-TKI combinations. PMID- 26898609 TI - Crizotinib-induced fatal fulminant liver failure. AB - Herein we describe a case of a 62-year-old female in good clinical condition with non-small-cell lung cancer who was treated with crizotinib. After 24 days of crizotinib therapy she presented with acute liver failure. Serum aspartate aminotransferase and alanine aminotransferase levels had increased from normal prior to crizotinib start to 2053 IU/L and 6194 IU/L, respectively. Total bilirubin and prothrombin time (PT-INR) increased up to 443 IU/L and 5.33, respectively, and symptoms of hepatic encephalopathy and hepatorenal syndrome emerged. Despite crizotinib discontinuation and intensive supportive therapy, the patient died 40 days after treatment with crizotinib was initiated due to acute liver failure with massive liver cell necrosis. PMID- 26898610 TI - Inter-reader reproducibility of dynamic contrast-enhanced magnetic resonance imaging in patients with non-small cell lung cancer treated with bevacizumab and erlotinib. AB - Objectives When evaluating anti-tumor treatment response by dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) it is necessary to assure its validity and reproducibility. This has not been well addressed in lung tumors. Therefore we have evaluated the inter-reader reproducibility of response classification by DCE-MRI in patients with non-small cell lung cancer (NSCLC) treated with bevacizumab and erlotinib enrolled in a multicenter trial. MATERIALS AND METHODS: Twenty-one patients were scanned before and 3 weeks after start of treatment with DCE-MRI in a multicenter trial. The scans were evaluated by two independent readers. The primary lung tumor was used for response assessment. Responses were assessed in terms of relative changes in tumor mean trans endothelial transfer rate (K(trans)) and its heterogeneity in terms of the spatial standard deviation. Reproducibility was expressed by the inter-reader variability, intra-class correlation coefficient (ICC) and dichotomous response classification. RESULTS: The inter-reader variability and ICC for the relative K(trans) were 5.8% and 0.930, respectively. For tumor heterogeneity the inter reader variability and ICC were 0.017 and 0.656, respectively. For the two readers the response classification for relative K(trans) was concordant in 20 of 21 patients (k=0.90, p<0.0001) and for tumor heterogeneity in 19 of 21 patients (k=0.80, p<0.0001). CONCLUSIONS: Strong agreement was seen with regard to the inter-reader variability and reproducibility of response classification by the two readers of lung cancer DCE-MRI scans. PMID- 26898611 TI - Impact of preoperative 18F-FDG PET/CT on survival of resected mono-metastatic non small cell lung cancer. AB - OBJECTIVES: Surgery has been available for the treatment of mono-metastatic, non small cell lung cancer (NSCLC) and promising overall survival was observed in some retrospective studies with selected patients. This study investigated whether the preoperative 18-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG-PET/CT) scan influences survival in this patient group. Furthermore we tried to identify other prognostic factors associated with survival and aimed to clarify if synchronous metastases are different from metachronous disease. METHODS: Between 1994 and 2012, 181 patients underwent resection for solitary metastases. Sixty-six patients underwent surgery after an initial FDG-PET/CT scan, whereas 115 patients underwent conventional preoperative staging by a spiral CT scan. RESULTS: The overall 5-year survival rate was 38.8%. The 5-year survival rates after preoperative evaluation by FDG PET/CT and by conventional CT were 58% and 33%, respectively (p=0.01). A higher 5 year survival rate was observed in patients without thoracic lymph node involvement (pN0: 44% vs. pN1-3: 33%, p=0.028). In patients with a solitary pulmonary metastasis, we observed a 5-year survival rate of 45.7%, whereas in patients with extrapulmonary metastases, the 5-year survival rate was 27.1% (p=0.001). In patients with a locally limited primary lung cancer according to the pT descriptor, we observed a 5-year survival rate of 53.1%, whereas in patients with a pT>1 descriptor, the 5-year survival rate was 33.6% (p=0.016). By multivariate analyses, we showed that preoperative FDG-PET/CT evaluation, no thoracic lymph node metastases, and sole pulmonary metastatic disease were favorable predictors of survival, whereas the time of metastasis (synchronous vs. metachronous) and maximum standardized uptake value was not. CONCLUSIONS: We conclude that resection of the primary tumor and metastasectomy for mono metastatic NSCLC can be performed after a comprehensive evaluation with FDG PET/CT. N-stage and the site of the oligometastases have a significant influence on overall survival. PMID- 26898612 TI - Cigarette smoke extract exposure induces EGFR-TKI resistance in EGFR-mutated NSCLC via mediating Src activation and EMT. AB - OBJECTIVES: The study aims to explore the molecular basis for the poor response of epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in EGFR mutated non-small cell lung cancer (NSCLC) patients with smoking history. Novel agent overcoming EGFR-TKI resistance had also been investigated. METHODS: The impact of cigarette smoke extract (CSE) on gefitinib sensitive PC-9 cells was evaluated using quantitative real-time PCR (qRT-PCR), western blot, CCK-8 assays, immunofluorescence staining, matrigel invasion assays and wound healing assays. RESULTS: Western blot and qRT-PCR presented that CSE stimulated the up-regulation of Vimentin and down-regulation of E-cadherin in PC-9 cells in concentration-and time-dependent manners through modulating Src phosphorylation. N-acetylcysteine (NAC) was capable of decreasing Src phosphorylation, abrogating changes of epithelial to mesenchymal transition (EMT) markers instigated by CSE. Immunofluorescence staining found that PC-9 cells displayed features of mesenchymal cells after CSE exposure, while PP2 and NAC could recover these changes. CCK-8 assays showed that CSE could increase the IC50 of PC-9 cells, while PP2 and NAC could abort the elevation of IC50 caused by CSE. Matrigel invasion assays and wound healing assays showed that CSE could increase the invasion and migration ability of PC-9 cells, which could be suppressed by NAC and PP2. CONCLUSION: CSE exposure induced EGFR-TKI resistance via mediating Src activation and EMT in NSCLC. NAC may alleviate smoking induced EGFR-TKI resistance through inhibiting Src activation and EMT reversal. NAC may be a promising adjuvant to reinforce the effect of EGFR-TKI. PMID- 26898613 TI - Sorafenib treatment for patients with RET fusion-positive non-small cell lung cancer. AB - BACKGROUND: RET fusions were recently identified in non-small cell lung cancer (NSCLC) and are considered as a potential therapeutic target of NSCLC. Sorafenib, a multi-kinase inhibitor, has potent anti-RET activity. We conducted a study to evaluate the efficacy of sorafenib in a small number of patients with RET fusion positive NSCLC. MATERIALS AND METHODS: Eligible patients had advanced or recurrent NSCLC, were more than 20 years old, had undergone treatment with one or more previous chemotherapy regimens, had an Eastern Cooperative Oncology Group performance status 0-2, had adequate organ function, and provided informed consent. The presence of the RET fusion gene was confirmed by a split FISH assay. The patients were treated twice daily with 400mg of sorafenib taken orally. The treatment was continued until either disease progression or unacceptable toxicity. RESULTS: From March 2012 to April 2013, three patients were enrolled. The responses to sorafenib included one patient with stable disease (SD) and two patients with progressive disease (PD). One patient took sorafenib for twelve months. The most common toxicities were palmar-plantar erythrodysesthesia syndrome, hypertension, and diarrhea. CONCLUSION: Since sorafenib did not show dramatic responses, we suggest testing other RET inhibitors for the treatment of RET fusion-positive NSCLC. This study was registered at UMIN as trial number 000007515. PMID- 26898614 TI - The impact of clinical parameters on progression-free survival of non-small cell lung cancer patients harboring EGFR-mutations receiving first-line EGFR-tyrosine kinase inhibitors. AB - OBJECTIVES: In daily practice, some patients with certain clinical characteristics may have better responses to the administration of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs). It is therefore reasonable to stratify and weigh the importance of these clinical parameters which may not only affect patients' responses to TKIs but also progression-free survival (PFS) other than the impact of EGFR mutation status per se. MATERIALS AND METHODS: This retrospective study evaluated EGFR-mutant, non-small cell lung cancer patients who received EGFR-TKIs as a first-line therapy between January 2011 and December 2013. Several potential prognostic factors were analyzed with respect to PFS, and the results of this analysis were validated in another time cohort. RESULTS: A total of 262 patients were included in the study. Age <= 40 years, uncommon EGFR mutations, poor performance status, more sites of distal metastasis, and blood lymphocyte to monocyte ratio <= 3 were independently associated with poor PFS. These five factors were included in a scoring system and three prognostic groups A, B, and C, were formed based on total scores of 0 1, 2, and >= 3, respectively. In the test group, the PFS was 15.7 month, 9.3 month, and 4.0 month in groups A, B, and C, respectively (p<0.001). Between the test and validation groups, no significant differences were found in each one of the three prognostic groups. CONCLUSIONS: The scoring system appears valid and reproducible for PFS prognosis in EGFR-mutant patients who received first-line EGFR-TKIs. PMID- 26898615 TI - K-RAS mutations indicating primary resistance to crizotinib in ALK-rearranged adenocarcinomas of the lung: Report of two cases and review of the literature. AB - The paradigm of mutually exclusive alterations among oncogenic drivers in non small-cell lung cancer (NSCLC) is challenged by the increasing evidence of detection of two or more driver alterations in the same tumor using highly sensitive molecular assays. We report here two cases of ALK-rearranged adenocarcinomas harboring concomitant exon 2 K-RAS mutations (G13D and Q61H). The patients, a 49-year-old smoker man and a 59-year-old non-smoking woman, experienced a rapid disease progression and primary resistance to crizotinib. Search for similar cases in the literature reveals that concomitant K-RAS mutations and ALK rearrangement occur in a subset of NSCLC and seems to lead to resistance to crizotinib. Among 8 similar cases receiving crizotinib previously reported (4 in first line and 4 in second line), 1 had a partial response, 1 stable disease and 6 disease progression. One patient still had progression disease when switching to ceritinib. At the end, K-RAS mutations seem to represent a negative predictive marker in ALK-rearranged adenocarcinomas treated with ALK inhibitor. PMID- 26898616 TI - Next-generation epidermal growth factor receptor tyrosine kinase inhibitors in epidermal growth factor receptor -mutant non-small cell lung cancer. AB - Since the discovery of sensitizing EGFR mutations as a predictive marker of sensitivity to EGFR tyrosine kinase inhibitors (TKIs), the field of targeted therapy in non-small cell lung cancer (NSCLC) has been revolutionized. Patients harbouring these sensitizing mutations treated with EGFR TKI have derived significant clinical outcome when compared with standard platinum based chemotherapy doublets. However disease progression invariably occurs at a median of about 9-13 months from initiation treatment, if acquired resistance commonly due to the development of EGFR T790M mutation. A novel class of "third generation" EGFR TKIs have been developed that is sensitising and T790M mutant specific whilst sparing WT EGFR, representing a significant breakthrough in the treatment in NSCLC patients with acquired resistance harboring these genotypes. Early phase clinical data suggest the third generation EGFR TKIs such as osimertinib, rociletinib, and HM61713 are highly efficacious and well tolerated. Another promising class of EGFR TKI such as AZD3759 has been designed to penetrate blood brain barrier to treat brain metastases and leptomeningeal disease and has showed promising responses in patients with brain metastases. Acquired resistance to third generation EGFR TKIs has been reported including EGFR C797S. Given its non-invasive nature, plasma ctDNA is being explored as a possible approach to detect T790M mutation and to also inform on novel molecular mechansims of tertiary resistance to third generation EGFR TKIs. An understanding of the mechanisms of acquired resistance to the third-generation EGFR TKIs will greatly aid in the development of the next generation of EGFR TKIs. PMID- 26898617 TI - Association of pharmacokinetics and pharmacogenomics with safety and efficacy of gefitinib in patients with EGFR mutation positive advanced non-small cell lung cancer. AB - OBJECTIVES: Gefitinib is a potent epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor and is a key drug for patients with EGFR mutation positive advanced non-small cell lung cancer (NSCLC). The pharmacokinetics of orally administered gefitinib varies greatly among patients. We prospectively evaluated the association of pharmacokinetics and pharmacogenomics with the safety and efficacy of gefitinib in patients with EGFR mutation-positive advanced NSCLC. PATIENTS AND METHODS: Pharmacokinetics was evaluated with samples of peripheral blood obtained on day 1 before treatment and 1, 3, 5, 8, and 24h after gefitinib (250 mg per day) was administered and on days 8 and 15 as the trough values. The plasma concentration of gefitinib was analyzed with high-performance liquid chromatography. The genotypes of ABCG2, ABCB1, CYP3A4, CYP3A5, and CYP2D6 genes were analyzed with direct sequencing. RESULTS: The subjects were 35 patients (21 women; median age, 72 years; range, 53 to 90 years) with stage IV adenocarcinoma harboring EGFR mutations. The median peak plasma concentration (Cmax) was 377 (range, 168-781)ng/mL. The median area under the curve (AUC) of the plasma concentration of gefitinib from 0 to 24h was 4893 (range, 698-13991) ng/mL h. The common adverse events were skin toxicity (68% of patients), diarrhea (46%), and liver injury (63%). One patient died of drug-induced interstitial lung disease (ILD). The overall response rate was 82.9% (95% confidence interval, 66.4%-93.4%). The median progression-free survival time was 10 months, and the median survival time was 25 months. The pharmacokinetics and pharmacogenomics were not associated with significantly different toxicities, response rates, or survival times with gefitinib. However, the AUC and Cmax were highest and the trough value on day 8 was the second highest in one patient who died of drug induced ILD. CONCLUSION: Elevated gefitinib exposure might be associated with drug-induced ILD. PMID- 26898619 TI - Small-cell lung cancer in never-smokers: A case series. AB - Small-cell lung cancer (SCLC) is closely correlated with smoking and only sporadic cases have been reported in non-smoking patients. Environmental tobacco smoke and/or occupational risk factors have been suggested as possible causes of lung cancer in this subset of patients. However, particularly in relation to SCLC there is not enough reliable information. All patients with lung cancer in follow up for a period of three-months at the Pulmonology Unit of Coimbra University Hospital were retrospectively assessed. From a total of 303 patients, 35 had SCLC, 4 of which were never-smokers and their clinical cases are hereby presented. A detailed questionnaire was given to all patients, which excluded second-hand smoking or occupational hazards. They were all female with a mean age of 63.0 +/- 15.7 years. The most frequent complaints were cough, dyspnoea, anorexia and significant weight loss. Diagnosis was obtained by transbronchial biopsies in all cases. Two patients had locally advanced disease and the other two had extensive-disease due to distant metastases. Treatment approaches included first-line chemotherapy with platin and etoposide duplet and partial remission was achieved in half the cases. All patients died; mean survival was 15.8 +/- 3.8 months. Further studies are needed for a better understanding of the pathogenicity of non-smoking related SCLC and we hope that this case series with its meticulous exclusion of potential risk factors will be a useful contribution. PMID- 26898618 TI - Medical treatment involving investigational drugs and genetic profile of thymic carcinoma. AB - BACKGROUND: Thymic carcinoma is a rare neoplasm of the thymus, and information regarding its genetic profile and optimal medical treatment is limited. We sought to characterize the genetic profile of thymic carcinoma and to evaluate the efficacy of various medical treatments, including treatment with tyrosine kinase inhibitors (TKIs), cytotoxic agents, and immune checkpoint inhibitors. METHODS: We retrospectively reviewed medical records of 64 consecutive patients with thymic carcinoma at the National Cancer Center Hospital between April 1973 and March 2014. We analyzed treatment course of patients who underwent medical treatment involving investigational drugs. For patients with available tissue samples, targeted sequencing of 50 cancer-related genes using next-generation sequencing was performed. RESULTS: Thirty-six patients had received chemotherapy. Median progression-free survival in patients receiving first-line chemotherapy was 7.07 months (95% confidence interval, 5.67-8.93). Median survival time was 32.6 months (95% confidence interval, 23.2-43.4). As second- or later-line chemotherapy, a total of 13 patients were treated with 24 investigational drugs, including 8 multi-targeted TKIs, 5 cytotoxic agents, and 2 immune checkpoint inhibitors. Six (24%) of the patients treated with investigational drugs maintained disease control for at least 6 months. Tissue samples of 52 patients (81.3%) were available for targeted sequencing, consisting of 52 formalin-fixed, paraffin-embedded (FFPE) and 16 fresh frozen tissue samples. The genetic alterations of TP53, KRAS, FBXW7, and NRAS were detected in 7 patients (13.5%), and no KIT mutations were noted. CONCLUSIONS: Multi-targeted TKIs exhibited potential clinical efficacy for previously-treated thymic carcinoma. The frequency of genetic alterations in this study was low, with no apparent relationship with the efficacy of chemotherapy. PMID- 26898620 TI - Induction therapy followed by surgical resection in Stage-III thimic epithelial tumors: Long-term results from a multicentre analysis of 108 cases. AB - INTRODUCTION: So far no specific oncological strategies have been validated for locally-advanced epithelial thymic tumors (TETs). We herein report the long-term results of a large multicentric experience adopting a multimodal treatment. METHODS: From 01/1990 to 12/2010, the clinical data of 108 Masaoka Stage-III TETs patients surgically treated after induction therapy (IT) were retrospectively reviewed. Different IT-regimens were administered: ADOC (32 pts); PAC (38 pts); CEE (38 pts). Radiotherapy was concurrently used in 5 patients only. The end points of the study were the evaluation of: (1) resectability; (2) overall long term survival (LTS) and disease-free survival (DFS); and (3) independent prognostic factors. The Mann-Whitney and Fisher's exact tests were applied to test the associations. Survival analysis was performed by the Kaplan-Meier method and log-rank test. RESULTS: Mean age and male/female ratio were 51 +/- 13 years and 61/47, respectively. World Health Organization (WHO) histotype was: A in 6 pts (5.6%), AB in 18 (16.7%), B1 in 15 (13.9%), B2 in 26 (24.1%), B3 in 23 (21.3%), and thymic carcinoma in 20 (18.5%). Thirty-day mortality was 1.8%. A total of 81 (75%) had R0-resection, 11 (10.2%) R1 and 16 (14.8%) R2-resection. Adjuvant therapy was performed in 71 patients. During the follow-up a relapse of disease was observed in 38 pts(35.2%). Five-years DFS and LTS were 69.3% and 79.3%, respectively. At univariate analysis, WHO-type B3/C ("high-risk") TETs (p=0.001) and recurrence of disease (p=0.02) were predictors of poor LTS while only a slight correlation was found for R-status and "CHT-regimen type" (p=0.097 and p=0.067, respectively). At multivariate analysis WHO "high-risk" TETs (H.R.5.73;C.I.:1.77-18.57) and ADOC-regimen (H.R.2.84;C.I.:1.37-5.86) were independent predictors of poor survival. CONCLUSIONS: A multimodal treatment for Stage-III thymic tumors may achieve a rewarding survival. WHO-Histology seems to be the most important prognostic factor. PMID- 26898622 TI - Two novel HLA-A alleles: A*24:258 and A*24:305 were identified in Chinese individuals. AB - Both HLA-A*24:258 and HLA-A*24:305 differ from HLA-A*24:01:01:01 by single nucleotide substitutions. PMID- 26898621 TI - Quality of life results from the phase 3 REVEL randomized clinical trial of ramucirumab-plus-docetaxel versus placebo-plus-docetaxel in advanced/metastatic non-small cell lung cancer patients with progression after platinum-based chemotherapy. AB - OBJECTIVES: REVEL demonstrated that ramucirumab+docetaxel (RAM+DTX) improved overall survival, progression-free survival, and objective response rate in patients with advanced/metastatic non-small cell lung cancer with progression after platinum-based chemotherapy. This analysis examined quality of life (QoL) as assessed by the Lung Cancer Symptom Scale (LCSS) and clinician-reported functional status. MATERIALS AND METHODS: The LCSS includes 6 symptom and 3 global items measured on a 0-100-mm scale; higher scores represent greater symptom burden. LCSS and ECOG PS data were collected at baseline, every 3-week cycle, the summary visit, and at the 30-day follow-up. LCSS total score and Average Symptom Burden Index (ASBI) were calculated. The primary analysis compared time to deterioration (TtD) between treatment arms for all individual items and summary scores, defined as increase from baseline by >= 15 mm using the Kaplan-Meier method and Cox regression. TtD to ECOG PS >= 2 was analyzed. RESULTS: There were 1253 patients randomized to receive RAM+DTX or placebo+docetaxel (PL+DTX). Across all assessments, LCSS compliance was approximately 75% and balanced across arms. The mean (SD) baseline LCSS total score was 27.3mm (17.08 mm) on RAM+DTX and 29.6mm (17.59 mm) on PL+DTX. At 30-day follow-up, mean (SD) LCSS total score was 32.0 (19.03) on RAM+DTX and 32.5 (19.87) on PL+DTX. The TtD for all LCSS scores was similar between treatment arms. Stratified HRs (95% CI) for LCSS total score and ASBI were HR=0.99 (0.81, 1.22), p=0.932 and HR=0.93 (0.75, 1.15), p=0.514 with approximately 70% of patients censored. TtD to PS >= 2 was similar between treatment arms (HR=1.03 [95% CI: 0.85, 1.26], p=0.743) with approximately two-thirds of the patients censored. CONCLUSION: In addition to improvement of clinical efficacy outcomes demonstrated in REVEL, these results suggest that adding ramucirumab to docetaxel did not impair patient QoL, symptoms, or functioning. PMID- 26898623 TI - Treatment of Corticosteroid-Resistant Vascular Tumors Associated with the Kasabach-Merritt Phenomenon in Infants: An Approach with Transcatheter Arterial Embolization Plus Vincristine Therapy. AB - PURPOSE: To investigate the effectiveness and application of transcatheter arterial embolization (TAE) plus systemic vincristine for treatment of corticosteroid-resistant vascular tumors associated with Kasabach-Merritt phenomenon in infants. MATERIALS AND METHODS: TAE was performed in 17 infants (average age, 4.3 mo +/- 2.4; range, 1-10 mo) with corticosteroid-resistant vascular tumors associated with Kasabach-Merritt phenomenon, followed by intravenous vincristine once weekly for systemic chemotherapy. The effects and complications were observed and evaluated after a cycle (1 cycle: TAE plus treatment with vincristine every 4 weeks). Cycles were repeated in infants with platelet counts < 150 * 10(9)/L. RESULTS: In 17 patients, 36 treatment cycles were successfully performed. The platelet count for all patients increased to >= 100 * 10(9)/L for the first time at 6.0 days +/- 3.5; the platelet level of 15 infants was maintained at levels > 150 * 10(9)/L at 57.5 days +/- 16.5. Before treatment, two infants had a normal fibrinogen level (2.21 g/L and 2.34 g/L); the fibrinogen level in the other 15 infants was first found to be increased to >= 2.0 g/L at 7.0 days +/- 3.4 and was stabilized at levels > 2.0 g/L at 55.9 days +/- 13.8 after treatment. Complications were graded as major in four cases and as minor in 13 cases. CONCLUSIONS: TAE plus vincristine can rapidly improve levels of platelets and fibrinogen, and it is an effective method for treatment of corticosteroid-resistant vascular tumors associated with Kasabach-Merritt phenomenon in infants. PMID- 26898624 TI - Outcomes of Percutaneous Cholecystostomy in the Presence of Ascites. AB - PURPOSE: To evaluate whether the presence of ascites increases complications following placement of percutaneous cholecystostomy tubes (PCTs). MATERIALS AND METHODS: Retrospective review of all transhepatic PCTs placed between January 2005 and June 2014 was performed: 255 patients were included (median age of 65 y; range, 20-95 y). Of these patients, 97 had ascites and 158 had no ascites or only pelvic fluid. In all, 115 patients had calculous cholecystitis (45%), 127 had acalculous cholecystitis (50%), and 13 had common bile duct obstruction (5%). The primary outcome of interest was all complications, including bile peritonitis, pericatheter leakage requiring PCT change, pericholecystic abscess formation, drain dislodgment, or death from biliary sepsis within 14 days of initial PCT insertion. RESULTS: The overall complication rate was 11% among patients with ascites (n = 11), compared with 10% in those without (n = 16; P = .834). No difference was found between the two groups in any one complication. The overall outcome of PCT drainage differed between groups, with significantly shorter survival times in patients with ascites. Patients with ascites underwent cholecystectomy less often than patients without ascites (21% vs 39%; P = .002). Likewise, patients with ascites were more likely than those without ascites to die with the PCT in place (49% vs 25%; P = .001). CONCLUSIONS: Frequencies of complications following PCT insertion were similar in patients with and without ascites. Additionally, the overall complication rate was low and not significantly different between the two groups. These observations support the use of PCT placement in patients with ascites. PMID- 26898625 TI - Chronic kidney disease: Low birth weight and the global burden of kidney disease. AB - Low birth weight (LBW) and intrauterine growth restriction are major contributors to the global burden of non-communicable diseases. A Norwegian registry study has confirmed that LBW is associated with an increased risk of developing end-stage renal disease by 40 years of age, which could not be explained by familial factors. PMID- 26898629 TI - Diabetic nephropathy: MiR-23b protects against fibrosis in diabetic nephropathy. PMID- 26898631 TI - Solid-Supported Porphyrins Useful for the Synthesis of Conjugates with Oligomeric Biomolecules. AB - meso-Tris(pyridin-4-yl)(4-carboxyphenyl)porphyrin and 2-(1-hexyloxyethyl)-2 devinyl pyropheophorbide-a (Photochlor, HPPH) were amide-coupled to 1R,2S,3R,4R 2,3-dihydroxy-4-(hydromethyl)-1-aminocyclopentane and immobilized via an ester linkage to long chain alkyl amine-derivatized controlled pore glass (LCAA-CPG). The applicability of these supports (5 and 6) for the synthesis of porphyrin conjugates with oligomeric biomolecules was demonstrated using an automated phosphoramidite coupling chemistry. Cleavage from the support with concentrated ammonia gave the products, viz., porphyrin conjugates of oligonucleotides (7-9) and dendritic glycoclusters (10-13) and a cyclooctyne derivative (14) in 23-58% yield. In addition, the synthesized cyclooctyne derivative of meso-tris(pyridin-4 yl)(4-carboxyphenyl)porphyrin (14) was conjugated with an azidopropyl-modified hyaluronic acid (19). The hyaluronic acid-porphyrin conjugate (15) was radiolabeled with (64)Cu and its (15[(64)Cu]) receptor binding affinity to CD44 expressing tumor cells was evaluated. PMID- 26898632 TI - Prediction of new onset of resting pulmonary arterial hypertension in systemic sclerosis. AB - BACKGROUND: Early detection of pulmonary arterial hypertension (PH) is crucial in systemic scleroderma. However, predictors of new onset of resting PH during follow-up (FUPH) have been poorly explored. AIM: To determine whether nailfold videocapillaroscopy (NVC) grade and exercise echocardiographic variables are predictors of FUPH. METHODS: We prospectively enrolled 40 patients with systemic sclerosis (age 54+/-13 years; 68% women). All patients underwent graded semisupine exercise echocardiography and NVC. Baseline resting PH and FUPH were defined as systolic pulmonary arterial pressure (sPAP)>35 mmHg, and exercise induced PH (EIPH) as exercise sPAP>50 mmHg. RESULTS: Seventeen patients developed EIPH (43%). During follow-up (FU) (25+/-15 months), 11 patients without baseline PH developed FUPH (28%), all from the EIPH group. Patients with FUPH were significantly older (60+/-14 vs 50+/-12 years; P=0.04), had higher resting and exercise sPAP (30+/-4 vs 22+/-5 and 60+/-12 vs 40+/-11 mmHg, respectively; P<0.0001) and a higher exercise E/e' ratio (9.4+/-0.7 vs 5.8+/-0.4; P=0.0003) and presented more frequently NVC grade>2 (90% vs 35%; P=0.0009). After adjustment for age, resting sPAP, exercise sPAP and NVC grade>2 were associated with maximal resting sPAP during follow-up and FUPH (P<0.05). Patients with both EIPH and NVC grade>2 had a very high incidence of FUPH (82%), and both variables remained strongly associated with FUPH after adjustment for age (hazard ratio 11.6, 95% confidence interval 2.4-55.3; P=0.002). CONCLUSION: Exercise echocardiography and NVC can identify a subgroup of patients with systemic sclerosis who are at risk of developing FUPH. PMID- 26898633 TI - Midodrine hydrochloride and unexpected improvement in hypertrophic cardiomyopathy symptoms. PMID- 26898634 TI - Novel materials and devices in the transcatheter management of congenital heart diseases--the future comes slowly (part 1). AB - Management of congenital defects of the heart and great vessels constitutes the largest part of paediatric cardiology practice. Most of these defects require interventions, either corrective or palliative, to guarantee patient survival, symptom relief and/or better quality of life. Interventions can be performed either surgically or transcatheter percutaneously. The surgical repairs are invasive, with long-term results often being suboptimal for complex lesions and after the use of grafts, especially in small patients. Nowadays, various transcatheter devices allow much less invasive percutaneous management in some carefully selected patients with congenital heart disease. However, the currently available materials and devices are only suitable for a small proportion of children, while the majority of young patients with cardiac defects still need surgery, as no transcatheter alternatives exist. There are, however, numerous new biomaterials, devices and technologies that have the potential to expand the transcatheter approach to a much broader spectrum of congenital cardiovascular lesions and conditions. In this three-part review, we describe new advances in transcatheter devices and materials, which promise to extend the application of the percutaneous approach to younger and more complex patient groups with congenital heart disease. The first part focuses on new possibilities for the transcatheter treatment of vascular stenoses in growing patients and the closure of intracardiac defects. PMID- 26898635 TI - Long-term prognosis of left-sided native-valve Staphylococcus aureus endocarditis. AB - BACKGROUND: Staphylococcus aureus infective endocarditis (SAIE) is a serious and common disease. AIMS: To assess the clinical and echocardiographic characteristics and prognostic factors of left-sided native-valve SAIE, and to compare these characteristics between two periods (1990-2000 vs. 2001-2010). METHODS: This was a retrospective analysis of 162 cases of left-sided native valve SAIE among 1254 patients hospitalized for infective endocarditis (IE) between 1990 and 2010. RESULTS: SAIE represented 18.1% of all cases of IE and 22.9% of cases of native-valve IE. Complications included heart failure in 44.7% of cases, acute renal failure in 23.3%, sepsis in 28.5%, neurological events in 35.8%, systemic embolic events in 54.9% and in-hospital mortality in 25.3%. Factors associated with in-hospital mortality were heart failure (odds ratio [OR] 2.5; P=0.04) and sepsis (OR 5.3; P=0.001). Long-term 5-year survival was 49.6+/ 4.9%. Factors associated with long-term mortality were heart failure (OR 1.7; P=0.032), sepsis (OR 3; P=0.0001) and delayed surgery (OR 0.43; P=0.003). Comparison of the two periods revealed a significant increase in bivalvular involvement, valvular incompetence and acute renal failure from 2001 to 2010. No significant difference was observed in terms of in-hospital mortality rates (28.1% vs. 23.5%; P=0.58) and long-term 5-year survival (45.0+/-6.6% vs. 57.1+/ 6.4%; P=0.33). CONCLUSION: Mortality as a result of left-sided native-valve SAIE remains high. Factors associated with in-hospital mortality are heart failure and sepsis. Factors associated with long-term mortality are heart failure, sepsis and delayed surgery. Despite progress in surgical techniques, in-hospital mortality and long-term mortality have not decreased significantly between the two periods. PMID- 26898636 TI - Dietary lysine requirement for 7-16 kg pigs fed wheat-corn-soybean meal-based diets. AB - Two experiments were conducted to determine the lysine requirement of weaned pigs [Duroc * (Yorkshire * Landrace)] with an average initial BW of 7 kg and fed wheat corn-soybean meal-based diets. The experiments were conducted for 21 days during which piglets had free access to diets and water. Average daily gain (ADG), average daily feed intake (ADFI) and gain to feed ratio (G:F) were determined on day 7, 14 and 21. Blood samples were collected on day 0 and 14 to determine plasma urea nitrogen (PUN) concentration. In experiment 1, 96 weaned pigs were housed four per pen and allocated to four dietary treatments with six replicates per treatment. The diets contained 0.99%, 1.23%, 1.51% and 1.81% standardized ileal digestible (SID) lysine, respectively, corrected analysed values. The rest of the AA were provided to meet the ideal AA ratio for protein accretion. Increasing dietary lysine content linearly increased (p < 0.05) ADG and G:F. In experiment 2, 90 piglets were housed three per pen and allocated to five dietary treatments with six replicates per treatment. The five diets contained 1.03%, 1.25%, 1.31%, 1.36% and 1.51% SID lysine, respectively, corrected analysed values. Increasing dietary lysine content linearly increased (p < 0.05) G:F, linearly decreased (p < 0.05) day-14 PUN and quadratically (p < 0.05) increased ADG and ADFI. The ADG data from experiment 2 were subjected to linear and quadratic broken-lines regression analyses, and the SID lysine requirement was determined to be 1.29% and 1.34% respectively. On average, optimal dietary SID lysine content for optimal growth of 7-16 kg weaned piglets fed wheat-corn-SBM based diets was estimated to be 1.32%; at this level, the ADG and ADFI were 444 and 560 g, respectively, thus representing an SID lysine requirement, expressed on daily intake basis as, 7.4 g/day or 16.76 mg/g gain. PMID- 26898637 TI - Use of lead-210 as a novel tracer for lead (Pb) sources in plants. AB - Lead (Pb) released from anthropogenic sources and stored in environmental repositories can be a potential source for secondary pollution. Here we develop a novel approach for tracking Pb from atmospheric deposition and other sources in the environment using fallout (210)Pb as a tracer, and apply the method to samples collected from Richmond Park, London, the UK. The mean ratio of (210)Pb to total Pb in atmospheric depositions collected from a site adjacent to the park during August-October 2012 was 96 Bq mg(-1), while the ratio in surface soils from the park was typically an order of magnitude lower. The difference between these values made it possible to trace the source of Pb in the plants. The (210)Pb/Pb ratios in plants varied from 0 to 34 Bq mg(-1) indicating different levels of Pb absorption from the atmosphere. The ratio in mosses had an average value of 22 Bq mg(-1). This suggests that only around 20% of the Pb they contain was from direct atmospheric deposition, revealing possible limitations in the use of terrestrial mosses for monitoring atmospheric pollution. As well as tracking sources, variations in the (210)Pb/Pb ratio can also reveal ways in which Pb is transferred within plants. PMID- 26898639 TI - T helper 17 cells may drive neuroprogression in major depressive disorder: Proposal of an integrative model. AB - The exact pathophysiology of major depressive disorder (MDD) remains elusive. The monoamine theory, which hypothesizes that MDD emerges as a result of dysfunctional serotonergic, dopaminergic and noradrenergic pathways, has guided the therapy of this illness for several decades. More recently, the involvement of activated immune, oxidative and nitrosative stress pathways and of decreased levels of neurotrophic factors has provided emerging insights regarding the pathophysiology of MDD, leading to integrated theories emphasizing the complex interplay of these mechanisms that could lead to neuroprogression. In this review, we propose an integrative model suggesting that T helper 17 (Th17) cells play a pivotal role in the pathophysiology of MDD through (i) microglial activation, (ii) interactions with oxidative and nitrosative stress, (iii) increases of autoantibody production and the propensity for autoimmunity, (iv) disruption of the blood-brain barrier, and (v) dysregulation of the gut mucosa and microbiota. The clinical and research implications of this model are discussed. PMID- 26898638 TI - Using Length of Stay to Control for Unobserved Heterogeneity When Estimating Treatment Effect on Hospital Costs with Observational Data: Issues of Reliability, Robustness, and Usefulness. AB - OBJECTIVE: To evaluate the sensitivity of treatment effect estimates when length of stay (LOS) is used to control for unobserved heterogeneity when estimating treatment effect on cost of hospital admission with observational data. DATA SOURCES/STUDY SETTING: We used data from a prospective cohort study on the impact of palliative care consultation teams (PCCTs) on direct cost of hospital care. Adult patients with an advanced cancer diagnosis admitted to five large medical and cancer centers in the United States between 2007 and 2011 were eligible for this study. STUDY DESIGN: Costs were modeled using generalized linear models with a gamma distribution and a log link. We compared variability in estimates of PCCT impact on hospitalization costs when LOS was used as a covariate, as a sample parameter, and as an outcome denominator. We used propensity scores to account for patient characteristics associated with both PCCT use and total direct hospitalization costs. DATA COLLECTION/EXTRACTION METHODS: We analyzed data from hospital cost databases, medical records, and questionnaires. Our propensity score weighted sample included 969 patients who were discharged alive. PRINCIPAL FINDINGS: In analyses of hospitalization costs, treatment effect estimates are highly sensitive to methods that control for LOS, complicating interpretation. Both the magnitude and significance of results varied widely with the method of controlling for LOS. When we incorporated intervention timing into our analyses, results were robust to LOS-controls. CONCLUSIONS: Treatment effect estimates using LOS-controls are not only suboptimal in terms of reliability (given concerns over endogeneity and bias) and usefulness (given the need to validate the cost-effectiveness of an intervention using overall resource use for a sample defined at baseline) but also in terms of robustness (results depend on the approach taken, and there is little evidence to guide this choice). To derive results that minimize endogeneity concerns and maximize external validity, investigators should match and analyze treatment and comparison arms on baseline factors only. Incorporating intervention timing may deliver results that are more reliable, more robust, and more useful than those derived using LOS-controls. PMID- 26898640 TI - A pilot-scale forward osmosis membrane system for concentrating low-strength municipal wastewater: performance and implications. AB - Recovery of nutrients and energy from municipal wastewater has attracted much attention in recent years; however, its efficiency is significantly limited by the low-strength properties of municipal wastewater. Herein, we report a pilot scale forward osmosis (FO) system using a spiral-wound membrane module to concentrate real municipal wastewater. Under active layer facing feed solution mode, the critical concentration factor (CCF) of this FO system was determined to be 8 with 0.5 M NaCl as draw solution. During long-term operation at a concentration factor of 5, (99.8 +/- 0.6)% of chemical oxygen demand and (99.7 +/ 0.5)% of total phosphorus rejection rates could be achieved at a flux of 6 L/(m(2) h) on average. In comparison, only (48.1 +/- 10.5)% and (67.8 +/- 7.3)% rejection of ammonium and total nitrogen were observed. Cake enhanced concentration polarization is a major contributor to the decrease of water fluxes. The fouling also led to the occurrence of a cake reduced concentration polarization effect, improving ammonium rejection rate with the increase of operation time in each cycle. This work demonstrates the applicability of using FO process for wastewater concentrating and also limitations in ammonium recovery that need further improvement in future. PMID- 26898641 TI - How to manage sepsis associated with ureteral calculi? PMID- 26898642 TI - Impact of Structural Modification on the Photophysical Response of Benzoquinoline Fluorophores. AB - Structural influence on the photophysical behavior of two pairs of molecular systems from the biologically potent benzoquinoline family, namely, dimethyl-3-(4 chlorophenyl)-3,4-dihydrobenzo[f]-quinoline-1,2-dicarboxylate, dimethyl-3-(2,6 dichlorophenyl)-3,4-dihydrobenzo[f]quinoline-1,2-dicarboxylate and their corresponding dehydrogenated analogues has been investigated exploiting experimental as well as computational techniques. The study unveils that dehydrogenation in the heterocyclic rings of the studied quinoline derivatives modifies their photophysics radically. Experimental observations imply that the photophysical behavior of the dihydro analogues is governed by the intramolecular charge transfer (ICT) process. However, the ICT process is restricted significantly by the dehydrogenation of the heterocyclic rings. Computational exertion leads to the proposition that the change in the electronic distribution in these molecular systems on dehydrogenation is the rationale behind the dramatic modification of their photophysics. PMID- 26898643 TI - EGCG decreases binding of calcium oxalate monohydrate crystals onto renal tubular cells via decreased surface expression of alpha-enolase. AB - Crystal retention on tubular cell surface inside renal tubules is considered as the earliest and crucial step for kidney stone formation. Therapeutics targeting this step would cease the development of kidney stone. This study thus aimed to investigate the potential role of epigallocatechin-3-gallate (EGCG), a major antioxidant found in green tea leaves, in the reduction of calcium oxalate monohydrate (COM) crystal binding onto renal tubular cells. Pretreatment of the cells with EGCG for up to 6 h significantly diminished crystal-binding capability in a dose-dependent manner. Indirect immunofluorescence assay without and with cell permeabilization followed by laser-scanning confocal microscopy revealed that EGCG significantly reduced surface expression of alpha-enolase, whereas its intracellular level was increased. Western blot analysis confirmed such contradictory changes in membrane and cytosolic fractions of EGCG-treated cells, whereas the total level in whole cell lysate remained unchanged. Moreover, overexpression of surface alpha-enolase and enhancement of cell-crystal adhesion induced by 10 mM sodium oxalate were completely abolished by EGCG. Taken together, these data indicate that EGCG decreases binding of COM crystals onto renal tubular cells by decreasing the surface expression of alpha-enolase via re localization or inhibition of alpha-enolase shuttling from the cytoplasm to the plasma membrane. These findings may also explain the effects of EGCG in reducing COM crystal deposition in previous animal models of kidney stone disease. Thus, EGCG may be useful for the prevention of new or recurrent stone formation. PMID- 26898644 TI - Spectroscopic and biological activity studies of the chromium-binding peptide EEEEGDD. AB - While trivalent chromium has been shown at high doses to have pharmacological effects improving insulin resistance in rodent models of insulin resistance, the mechanism of action of chromium at a molecular level is not known. The chromium binding and transport agent low-molecular-weight chromium-binding substance (LMWCr) has been proposed to be the biologically active form of chromium. LMWCr has recently been shown to be comprised of a heptapeptide of the sequence EEEEDGG. The binding of Cr(3+) to this heptapeptide has been examined. Mass spectrometric and a variety of spectroscopic studies have shown that multiple chromic ions bind to the peptide in an octahedral fashion through carboxylate groups and potentially small anionic ligands such as oxide and hydroxide. A complex of Cr and the peptide when administered intravenously to mice is able to decrease area under the curve in intravenous glucose tolerance tests. It can also restore insulin-stimulated glucose uptake in myotubes rendered insulin resistant by treating them with a high-glucose media. PMID- 26898645 TI - Successful Implementation of HIV Preexposure Prophylaxis: Lessons Learned From Three Clinical Settings. AB - The past 3 years have marked a transition from research establishing the safety and efficacy of HIV preexposure prophylaxis (PrEP) to questions about how to optimize its implementation. Until recently, PrEP was primarily offered as part of randomized controlled trials or open-label studies. These studies highlighted the key components of PrEP delivery, including regular testing for HIV and other sexually transmitted infections (STIs), adherence and risk-reduction support, and monitoring for renal toxicity. PrEP is now increasingly provided in routine clinical settings. This review summarizes models for PrEP implementation from screening through initiation and follow-up, focusing on the strengths and weaknesses of three delivery systems: a health maintenance organization, an STI clinic, and a primary care practice. These early implementation experiences demonstrate that PrEP can be successfully delivered across a variety of settings and highlight strategies to streamline PrEP delivery in clinical practice. PMID- 26898646 TI - An integrative view of storage of low- and high-level visual dimensions in visual short-term memory. AB - Efficient performance in an environment filled with complex objects is often achieved through the temporal maintenance of conjunctions of features from multiple dimensions. The most striking finding in the study of binding in visual short-term memory (VSTM) is equal memory performance for single features and for integrated multi-feature objects, a finding that has been central to several theories of VSTM. Nevertheless, research on binding in VSTM focused almost exclusively on low-level features, and little is known about how items from low- and high-level visual dimensions (e.g., colored manmade objects) are maintained simultaneously in VSTM. The present study tested memory for combinations of low level features and high-level representations. In agreement with previous findings, Experiments 1 and 2 showed decrements in memory performance when non integrated low- and high-level stimuli were maintained simultaneously compared to maintaining each dimension in isolation. However, contrary to previous findings the results of Experiments 3 and 4 showed decrements in memory performance even when integrated objects of low- and high-level stimuli were maintained in memory, compared to maintaining single-dimension objects. Overall, the results demonstrate that low- and high-level visual dimensions compete for the same limited memory capacity, and offer a more comprehensive view of VSTM. PMID- 26898649 TI - Amorphous SiO2 surface models: energetics of the dehydroxylation process, strain, ab initio atomistic thermodynamics and IR spectroscopic signatures. AB - In this contribution, realistic amorphous SiO2 models of 2.1 * 2.1 nm with silanol densities ranging 1.1-7.2 OH per nm(2) are obtained by means of ab initio calculations via the dehydroxylation of a fully hydroxylated silica surface. The dehydroxyation process is considered to take place via direct condensation of adjacent silanol groups and silica migration steps. The latter reconstructions are needed in order to obtain highly dehydroxylated silica surfaces with favorable energetics and without the formation of defects. The obtained surface phase diagram of different silica models as a function of temperature and PH2O is able to correctly describe the silanol density under different conditions, and the IR spectroscopic signatures of the silanols are in qualitative agreement with the experiment. The amorphous silica models presented here have a high degree of heterogeneity as found from the big variability obtained in the energetics of the dehydroxylation steps. It was also found that the resulting average Si-O distance of the newly formed siloxane bridges serves as a descriptor of the strain introduced in the silica surface. All these factors can be crucial in order to simulate the activity of catalysts grafted onto silica with different silanol densities, especially the one containing ca. 1 OH per nm(2), which can serve as a model for the SiO2 surface pretreated under high vacuum and at 700 degrees C. PMID- 26898648 TI - How directions of route descriptions influence orientation specificity: the contribution of spatial abilities. AB - Previous studies found mental representations of route descriptions north-up oriented when egocentric experience (given by the protagonist's initial view) was congruent with the global reference system. This study examines: (a) the development and maintenance of representations derived from descriptions when the egocentric and global reference systems are congruent or incongruent; and (b) how spatial abilities modulate these representations. Sixty participants (in two groups of 30) heard route descriptions of a protagonist's moves starting from the bottom of a layout and headed mainly northwards (SN description) in one group, and headed south from the top (NS description, the egocentric view facing in the opposite direction to the canonical north) in the other. Description recall was tested with map drawing (after hearing the description a first and second time; i.e. Time 1 and 2) and South-North (SN) or North-South (NS) pointing tasks; and spatial objective tasks were administered. The results showed that: (a) the drawings were more rotated in NS than in SN descriptions, and performed better at Time 2 than at Time 1 for both types of description; SN pointing was more accurate than NS pointing for the SN description, while SN and NS pointing accuracy did not differ for the NS description; (b) spatial (rotation) abilities were related to recall accuracy for both types of description, but were more so for the NS ones. Overall, our results showed that the way in which spatial information is conveyed (with/without congruence between the egocentric and global reference systems) and spatial abilities influence the development and maintenance of mental representations. PMID- 26898647 TI - Operational momentum and size ordering in preverbal infants. AB - Recent evidence has shown that, like adults and children, 9-month-old infants manifest an operational momentum (OM) effect during non-symbolic arithmetic, whereby they overestimate the outcomes to addition problems, and underestimate the outcomes to subtraction problems. Here we provide the first evidence that OM occurs for transformations of non-numerical magnitudes (i.e., spatial extent) during ordering operations. Twelve-month-old infants were tested in an ordinal task in which they detected and represented ascension or descension in physical size, and then responded to ordinal sequences that exhibited greater or lesser sizes. Infants displayed longer looking time to the size change whose direction violated the operational momentum experienced during habituation (i.e., the smaller sequence in the ascension condition and the larger sequence in the descension condition). The presence of momentum for ordering size during infancy suggests that continuous quantities are represented spatially during the first year of life. PMID- 26898651 TI - Adenocarcinoma Arising From the Tip of the J-Pouch With Medically Refractory Crohn's Disease. PMID- 26898650 TI - LPS/TLR4-mediated stromal cells acquire an invasive phenotype and are implicated in the pathogenesis of adenomyosis. AB - The present study tested whether the LPS/TLR4 signal pathway in endometrial stromal cells is essential for the pathogenesis of adenomyosis. We tested the expression of TLR4, MD2 in the endometrium without adenomyosis (CE), the eutopic endometrium with adenomyosis (EuE) and the ectopic endometrium with adenomyosis (EE). We isolated the stromal cells from CE, EuE and EE (CESC, EuESC, EESC), treated with lipopolysaccharide (LPS) and TLR4 antagonist and detected the cell viability. And we also measured the key protein of the TLR4 signal pathway and inflammatory proliferation and invasive growth of experimental cells. We found that the viability of experimental cells treated with LPS was significantly greater than that of the non-treated cells, blocked by the TLR4 antagonist VIPER. TLR4 signal pathway and inflammatory proliferation and invasive growth of experimental cells stimulated by LPS, and it was inhibited by VIPER. This study suggested that stromal cells were activated by the TLR4 signalling pathway, which processed the cellular inflammatory proliferation and invasive growth involved in the pathogenesis of adenomyosis. PMID- 26898652 TI - Sessile Serrated Polyps are Precursors of Colon Carcinomas With Deficient DNA Mismatch Repair. AB - We investigated whether sessile serrated adenomas/polyps (SSA/Ps) are direct precursors of colorectal carcinomas. We identified colon carcinomas that arose from SSA/Ps among 2646 colorectal cancers included in the surgical pathology database at the Mayo Clinic (2006-2012). Molecular features of the serrated neoplasia pathway were analyzed in these tumors by immunohistochemical analyses of mutant BRAF (V600E) and MLH1 proteins. Among the 33 identified SSA/P associated colonic adenocarcinomas (median patient age, 75 y), 24 developed in women (73%), 31 were located in the proximal colon (94%), and 23 (69%) were TNM stage I or II. Thirty-one of the tumors (94%) expressed mutant BRAF; of these, 26 also had loss of MLH1 (79%), indicating deficient DNA mismatch repair of sporadic origin. Twenty-two of the tumors (67%) were interval cancers that were more common in women and did not differ significantly in TNM stage, BRAF mutation, or loss of MLH1. By histopathology, SSA/Ps that were associated with colon carcinomas contained frequent dysplasia (48%). Most cancers that arose from SSA/Ps were located on the right side of the colon and had mutant BRAF and loss of MLH1. These findings indicate that SSA/Ps are precursors of most sporadic colon carcinomas with deficient DNA mismatch repair. PMID- 26898653 TI - From last supper to self-initiated weight loss: Pretreatment weight change may be more important than previously thought. AB - OBJECTIVE: Evaluate the association between pretreatment and during-treatment weight change, as well as differences in self-regulation between those who gain weight, remain weight stable, and lose weight pretreatment. METHODS: Data from the first 6 months of a behavioral weight loss study were used. Participants (n = 283) were weighed at two assessment points (screening visit and baseline) prior to the start of treatment and at every treatment session. Participants were divided into those who gained weight, remained weight stable, or lost weight between the screening visit and the first treatment session. RESULTS: Pretreatment weight change was not significantly associated with during-treatment change. Weight change from the screening visit to month 6 was significantly different by category, with losses of 11% and 7% for those who lost and gained weight pretreatment, respectively. Weight change from first treatment session to month 6 was not different by category. Poorer self-regulation was associated with pretreatment weight gain and better self-regulation with pretreatment weight loss. CONCLUSIONS: Pretreatment weight change may not relate to success during behavioral weight loss treatment. Researchers should carefully consider when the "baseline" assessment takes place to reduce bias introduced by pretreatment weight change. Poorer self-regulation may place individuals at risk for weight gain prior to treatment. PMID- 26898654 TI - Mesenchymal Stem Cells for Ischemic Stroke: Progress and Possibilities. AB - Stroke is the most common neurological cause of morbidity and mortality in industrialized countries, afflicting 15 million people every year. The numbers are expected to increase, mostly due to aging populations. One in five stroke patients dies, and one in three are left with permanent disabilities. Although some acute phase therapies such as intravenous recombinant tissue plasminogen activator (rt-PA) andendovascular treatment have been shown to improve ischemic stroke outcome, these therapies are available only for a small proportion of patients. The use of stem cells to replace brain cells lost during stroke is a long-term goal, and one which is difficult to achieve given that transplanted cells must integrate and restore neural pathways to regain function of damaged parts of the brain. Over the past decade the use of mesenchymal stromal cells (MSCs) as therapy has emerged as a particularly attractive option. MSCs are a class of multipotent, self-renewing cells that give rise to differentiated progeny when implanted into appropriate tissues. Herein, we present a review of the application of MSCs in ischemic stroke, including the source of MSCs, the route and timing of their delivery into the brain and the endpoints measured. Experimental data of transplantation of MSCs in animal stroke models suggest an improved functional recovery. The transplantation of MSCs influences a wide range of events by modulating the inflammatory environment, stimulating endogenous neurogenesis and angiogenesis and reducing the formation of glial scar, although the precise, underlying mechanism of this phenomenon remains unknown. The results from early clinical trials highlight the need to optimize variables such as cell selection and route of administration in order to translate these results into safe and successful clinical applications. PMID- 26898655 TI - Computational Enzymology and Organophosphorus Degrading Enzymes: Promising Approaches Toward Remediation Technologies of Warfare Agents and Pesticides. AB - The re-emergence of chemical weapons as a global threat in hands of terrorist groups, together with an increasing number of pesticides intoxications and environmental contaminations worldwide, has called the attention of the scientific community for the need of improvement in the technologies for detoxification of organophosphorus (OP) compounds. A compelling strategy is the use of bioremediation by enzymes that are able to hydrolyze these molecules to harmless chemical species. Several enzymes have been studied and engineered for this purpose. However, their mechanisms of action are not well understood. Theoretical investigations may help elucidate important aspects of these mechanisms and help in the development of more efficient bio-remediators. In this review, we point out the major contributions of computational methodologies applied to enzyme based detoxification of OPs. Furthermore, we highlight the use of PTE, PON, DFP, and BuChE as enzymes used in OP detoxification process and how computational tools such as molecular docking, molecular dynamics simulations and combined quantum mechanical/molecular mechanics have and will continue to contribute to this very important area of research. PMID- 26898656 TI - Intralesional immunotherapy as a strategy to treat melanoma. AB - INTRODUCTION: Intralesional immunotherapy supplements systemic treatments and often achieves higher remission rates as compared to systemic therapy. Its indication is metastatic melanoma with limited tumor burden, particularly in loco regional metastasis and distant soft tissue metastasis. AREAS COVERED: This review describes intralesional immunotherapy with talimogene laherparepvec (T VEC), with velimogene aliplasmid (Allovectin-7) and with intralesional interleukin-2. These therapies function exclusively by activating the immune system. Furthermore, Rose Bengal and electrochemotherapy have been included, as bystander effects have been observed with these treatments. EXPERT OPINION: Objective remissions are achieved in a higher percentage with intralesional immunotherapies, such as intralesional interleukin-2 with up to 69% of complete remissions, as compared to systemic treatment. Therefore, intralesional immunotherapy may act as supplement in the armament against metastatic melanoma. In particular, for patients with multiple cutaneous and subcutaneous metastases (20->= 100) and in patients with subcutaneous bulky disease intralesional immunotherapy can improve the disease outcome. The exact role of intralesional immunotherapy in the age of immune checkpoint blockade has still to be determined. A number of clinical trials are on the way in order to better understand synergistic actions of intralesional and systemic immunotherapy. PMID- 26898657 TI - Phage display and Shiga toxin neutralizers. AB - The current work presents an overview of the use of phage display technology for the identification and characterization of potential neutralizing agents for Shiga toxins. The last major Shiga toxin-associated disease outbreak, which took place in Germany in 2011, showed the international community that Shiga toxins remain a serious threat to public health. This is also demonstrated by the lack of specific therapies against Shiga toxin-induced Hemolytic Uremic Syndrome (HUS). Since its inception, phage display technology has played a key role in the development of antigen-specific (poly)-peptides or antibody fragments with specific biological properties. Herein, we review the current literature regarding the application of phage display to identify novel neutralizing agents against Shiga toxins. We also briefly highlight reported discoveries of peptides and heavy chain antibodies (VHH fragments or nanobodies) that can neutralize the cellular damage caused by these potent toxins. PMID- 26898659 TI - Exploring the effect of the apolipoprotein E (APOE) gene on executive function, working memory, and processing speed during the early recovery period following traumatic brain injury. AB - INTRODUCTION: There is evidence that the e4 allele of the apolipoprotein E (APOE) gene is detrimental to cognitive function, but results from traumatic brain injury (TBI) populations are mixed. A possible explanation is that APOEe2 carriers have routinely been incorporated into APOEe4 and non-e4 groups, despite APOEe2 being proposed to have an ameliorative effect. Our primary aim was to investigate the influence of APOEe4 on cognitive impairment during early recovery following TBI, excluding the potential confound of APOEe2 possession. A secondary objective was to explore whether APOEe4 displays more pronounced effects in moderate to severe TBI and to consider the potential postinjury protective influence of the APOEe2 allele. METHOD: Participants who recently sustained a TBI (posttraumatic amnesia > 5 minutes) were assessed on measures of information processing speed, executive function, and working memory upon remission of posttraumatic amnesia. APOE genotype was determined by buccal saliva DNA extraction (APOEe4 n = 37, APOEe3 n = 92, APOEe2 n = 13). RESULTS: Stepwise multiple regressions were performed to compare APOEe4 carriers to APOEe3 homozygotes, with injury severity, age, and estimated premorbid IQ included in the first step. This model was found to significantly predict performance on all tasks, accounting for 17.3-24.3% of the variance. When APOEe4 status was added for the second step, there were no significant changes on any tasks (additional variance <1%). The effect of APOEe4 in moderate to severe TBI and the effect of APOEe2 were explored by analysis of covariance (ANCOVA), with no significant effects revealed. CONCLUSIONS: It is unlikely that APOE genotype influences cognitive function in the initial recovery period following TBI, regardless of injury severity. However, a more nuanced and long-term exploration of the effect of APOE genotype in the TBI population is warranted. PMID- 26898660 TI - Laboratory longevity and competitiveness of Dacus ciliatus Loew (Diptera: Tephritidae) following sub-sterilizing gamma irradiation. AB - The effect of a sub-sterilizing gamma radiation dose on Dacus ciliatus adults was investigated to assess the suitability of the sterile insect technique (SIT) as an alternative method to control this pest. Late pupae (48 h prior to adult emergence) from a laboratory strain were irradiated with 120 Gy of gamma rays emitted by a 60Co source. Following adult emergence, the mortality of irradiated and non-irradiated cohorts was recorded. Over a period of 50 days after emergence, no significant negative effects of irradiation upon the longevity of male or female laboratory flies were observed. A laboratory competitiveness study (Fried test), using irradiated laboratory and wild males at a ratio of 3:1 was conducted to assess the ability of irradiated males to reduce the egg hatch rates of a wild population. The overall competitiveness was found to be ca. 0.32, suggesting a reduced, but satisfactory, quality of irradiated laboratory as compared with wild males. Based on the above findings, we calculated and proposed effective male release ratios for field application of SIT against D. ciliatus. PMID- 26898661 TI - Computed tomographic arthrography of the normal dromedary camel carpus. AB - The aim of this prospective cadaveric study was to provide a detailed computed tomographic (CT) reference of the carpal joint in healthy dromedary camels. Twelve forelimbs of six apparently healthy camels were used. Computed tomographic imaging of 12 normal cadaveric camel carpal joints was performed before and after intra-articular administration of iodinated contrast medium. Transverse CT images were reconstructed in dorsal and parasagittal planes. The six carpal bones, the radial trochlea, and the proximal articular surface of the metacarpal bones were clearly visible on CT images with the bone setting window. Radiocarpal, carpometacarpal, transverse intercarpal, medial and lateral palmer intercarpal, middle intercarpal, accessory carpoulnar and medial and lateral collateral ligaments, carpal canal, joint capsule, and the extensor and flexor tendons were identified on CT images with the soft-tissue setting window. Postcontrast CT images provided better delineation of intercarpal ligaments, the capsular compartments and recesses. Results indicated that the osseous and the clinically important soft tissue structures of the dromedary camel carpal joint could be identified using CT and CT arthrography. The CT data of this study will serve as a basis for diagnosis of carpal problems in camels. PMID- 26898662 TI - Random amplified polymorphic DNA PCR in the teaching of molecular epidemiology. AB - In this article, we describe a basic practical laboratory designed for fifth-year undergraduate students of Microbiology as part of the Epidemiology course. This practice provides the students with the tools for molecular epidemiological analysis of pathogenic microorganisms using a rapid and simple PCR technique. The aim of this work was to assay RAPD-PCR technique in order to infer possible epidemiological relationships. The activity gives students an appreciation of the value of applying a simple molecular biological method as RAPD-PCR to a discipline-specific question. It comprises a three-session laboratory module to genetically assay DNAs from strains isolated from a food outbreak. (c) 2016 by The International Union of Biochemistry and Molecular Biology, 44(4):391-396, 2016. PMID- 26898658 TI - Gut Microbiota of Nonalcoholic Fatty Liver Disease. AB - The prevalence of nonalcoholic fatty liver disease has been rapidly increasing worldwide. It has become a leading cause of liver transplantation. Accumulating evidence suggests a significant role for gut microbiota in its development and progression. Here we review the effect of gut microbiota on developing hepatic fatty infiltration and its progression. Current literature supports a possible role for gut microbiota in the development of liver steatosis, inflammation and fibrosis. We also review the literature on possible interventions for NAFLD that target the gut microbiota. PMID- 26898663 TI - Tear film lipid layer: A molecular level view. AB - Human cornea is covered by an aqueous tear film, and the outermost layer of the tear film is coated by lipids. This so-called tear film lipid layer (TFLL) reduces surface tension of the tear film and helps with the film re-spreading after blinks. Alterations of tear lipids composition and properties are related to dry eye syndrome. Therefore, unveiling structural and functional properties of TFLL is necessary for understanding tear film function under both normal and pathological conditions. Key properties of TFLL, such as resistance against high lateral pressures and ability to spread at the tear film surface, are directly related to the chemical identity of TFLL lipids. Hence, a molecular-level description is required to get better insight into TFLL properties. Molecular dynamics simulations are particularly well suited for this task and they were recently used for investigating TFLL. The present review discusses molecular level organization and properties of TFLL as seen by these simulation studies. This article is part of a Special Issue entitled: Biosimulations edited by Ilpo Vattulainen and Tomasz Rog. PMID- 26898664 TI - Frequency, clinical manifestations, and outcomes of Staphylococcus lugdunensis Bacteremia in children. AB - BACKGROUND: Staphylococcus lugdunensis (S. lugdunensis) is known as a common cause of clinically significant infections in adults although the clinical importance of S. lugdunensis isolates from pediatric samples is less known. The aim of this study is to assess the incidence, characteristics, and outcomes of S. lugdunensis bacteremia (SLB) in children. METHODS: From January 2009 to March 2014, all blood culture isolates were retrospectively screened for S. lugdunensis. We analyzed the isolates for antimicrobial susceptibility and patients who had developed SLB by reviewing the electronic medical records. Additionally, we identified mecA and blaZ for available isolates by polymerase chain reaction (PCR). RESULTS: Of the 647 positive blood cultures during the period, 277 (42.8%) yielded coagulase negative Staphylococcus (CoNS), and 10 of 277 CoNS were S. lugdunensis (3.6% of all CoNS isolates). Of eight SLB episodes identified, seven (87.5%) were considered to have clinically significant bacteremia. All patients had underlying diseases, and all SLB were either healthcare-associated or hospital acquired. There was no infectious endocarditis (IE) development. All patients were treated with antibiotics and recovered without sequelae. We found that the isolates in our study showed higher antibiotic resistance to penicillin (8/8: 100%) and oxacillin (6/8: 75.0%) than previously reported. Among isolates available, we detected mecA in all four isolates resistant to oxacillin and blaZ in 5 of 6 isolates resistant to penicillin. CONCLUSIONS: S. lugdunensis is a rare but an important cause of bacteremia in children. PMID- 26898665 TI - Current status of extended spectrum beta-lactamase-producing Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis in Okinawa prefecture, Japan. AB - Enterobacteriaceae producing extended spectrum beta-lactamase (ESBL) are distributed worldwide. In this study, 114 ESBL-producing Enterobacteriaceae were isolated by analyzing 1672 clinical isolates of Enterobacteriaceae collected from an Okinawa prefectural hospital in Japan between June 2013 and July 2014. The overall prevalence of ESBL-producing Enterobacteriaceae was 6.8%; the prevalence of different bacterial species among the ESBL-producing isolates was as follows: 11.5% Escherichia coli (90 of 783 isolates), 6.2% Klebsiella pneumoniae (19 of 307 isolates), and 11.1% Proteus mirabilis (5 of 45 isolates). The ESBL types blaCTX-M-1, -3, -15, -2, -14, -27, and mutants of blaSHV-1 were detected. Among them, blaCTX-M-15 (33.3%), blaCTX-M-14 (27.8%) and blaCTX-M-27 (33.3%) were dominant in the E. coli isolates, whereas a blaSHV mutant which possessed four mutations (Tyr7Phe, Leu35Gln, Gly238Ser and Glu240Lys) in the amino acid sequence of SHV-1 dominated in the K. pneumoniae isolates (11 of 19, 57.9%). The pandemic E. coli ST131 clone was found to constitute 3.3% of the overall examined isolates and 62.2% of the ESBL-producing E. coli isolates. Our results suggest that the genetic combination of blaCTX-M, and blaSHV and antibiotics-resistant profile were different from that in other regions such as other areas of Japan, Asia, Europe, and North America, especially in the ESBL-producing K. pneumoniae isolates and in the E. coli B2-O25b-ST131 isolates possessing blaCTX-M-15 (40.7% of the E. coli B2-O25b-ST131 isolates). Taken together, our results indicate that the ESBL-producing Enterobacteriaceae in Okinawa, Japan, might be of a unique nature. PMID- 26898666 TI - Multi-azole resistant Aspergillus fumigatus harboring Cyp51A TR46/Y121F/T289A isolated in Japan. AB - Multi-azole resistant Aspergillus fumigatus carrying TR46/Y121F/T289A was isolated from a patient in Japan in Dec 2013. This strain grouped into the same clade of the ones which were clinically isolated in France and Germany. A. fumigatus harboring this mutation could be rapidly diffused outside the Eurasian continent. PMID- 26898667 TI - Genetic, phenotypic and matrix-assisted laser desorption ionization time-of flight mass spectrometry-based identification of anaerobic bacteria and determination of their antimicrobial susceptibility at a University Hospital in Japan. AB - The accuracies of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and the phenotypic method using VITEK 2 were compared to the accuracy of 16S rRNA sequence analysis for the identification of 170 clinically isolated anaerobes. The antimicrobial susceptibility of the isolates was also evaluated. Genetic analysis identified 21 Gram-positive species in 14 genera and 29 Gram-negative species in 11 genera. The most frequently isolated genera were Prevotella spp. (n = 46), Bacteroides spp. (n = 25) and Clostridium spp. (n = 25). MALDI-TOF MS correctly identified more isolates compared with VITEK 2 at the species (80 vs. 58%, respectively; p < 0.01) and genus (85 vs. 71%, respectively; p < 0.01) levels. More than 90% of the isolates of the three major genera identified (Prevotella, Bacteroides, and Clostridium species other than Clostridium difficile) were susceptible to beta-lactam/beta-lactamase inhibitor combinations, carbapenems, metronidazole and chloramphenicol. MALDI-TOF MS provided better identification results than VITEK2. Commonly used anti anaerobic agents indicated that the isolates of the three most frequently identified anaerobic genera exhibited good antimicrobial susceptibility. PMID- 26898668 TI - Successful treatment with intravesical cidofovir for virus-associated hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation: A case report and a review of the literature. AB - Virus-associated hemorrhagic cystitis (VAHC) is a formidable complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The standard management of severe VAHC after allo-HSCT has not been established. Intravenous administration of cidofovir (CDV), an acyclic nucleoside analogue with broad spectrum activity against DNA viruses, has been reported to be effective for VAHC, but it can cause severe renal toxicity. Here we report four cases who achieved clinical responses with intravesical instillation of CDV for severe VAHC after allo-HSCT. Median age was 57 years (40-63), and all were male. The underlying diseases were hematological malignancies. Three had received bone marrow transplantation, and one received cord blood transplantation twice. Conditioning regimen was myeloablative for one, and reduced-intensity for three. The viral types were BK virus and/or adenovirus. Two patients had received CDV intravenously prior to the intravesical therapy. A dose of intravesical CDV was 2 5 mg/kg. In all cases, symptoms of cystitis improved dramatically within a few days without showing any systemic adverse effects. The virological response was observed in two cases. This local therapy was effective even in the cases refractory to the intravenous CDV and a case with severe renal failure. Along with the review of literature, we propose that the intravesical instillation of CDV can be a therapeutic option for severe VAHC after allo-HSCT. PMID- 26898669 TI - Experience of 463 cases of gastric cancer from a single surgical center. AB - AIM: To evaluate clinical and histopathological changes of gastric cancer (GC) in the last fifteen years and analyze factors influencing overall survival. MATERIAL OF STUDY: We have retrospectively categorized patients submitted to surgery for GC from January 1996 to December 2010. The analysis focused on two periods: 1996 2003 (period 1) and 2004-2010 (period 2). RESULTS: There was an increase in age distribution of GC in period 2 (p=0.012). Significant increase of whole GC was observed in period 2 (p=0.01). Slight but significant changes in TNM stage were found: in group 2 there was a decrease in the rate of early GC and in advanced depth of tumor invasion; increase of lymph nodes involvement was also demonstrated. Overall survival (OS) had not changed from the first to the second period. There was a significant difference in OS calculated for Lauren histotype: from ten months to surgery, patients with diffuse histotype showed worse prognosis. DISCUSSION: The most important findings were an increase in lymph node involvement and a decrease in depth of tumor invasion, an higher percentage of whole type and a decrease in palliative surgery. Overall-survival hasn't change in the last fifteen years. These results confirms the importance of extent of lymph node dissection in the standard surgical approach of GC, the tumor stage and Lauren histotypes as the main prognostic factors in GC. CONCLUSION: This work confirms the dismal prognosis of GC and the need to increase diagnosis of early gastric cancer. KEY WORDS: Gastric cancer, Lauren histotype, Overall survivall. PMID- 26898670 TI - Quasi-Direct Optical Transitions in Silicon Nanocrystals with Intensity Exceeding the Bulk. AB - Comparison of the measured absolute absorption cross section on a per Si atom basis of plasma-synthesized Si nanocrystals (NCs) with the absorption of bulk crystalline Si shows that while near the band edge the NC absorption is weaker than the bulk, yet above ~ 2.2 eV the NC absorbs up to 5 times more than the bulk. Using atomistic screened pseudopotential calculations we show that this enhancement arises from interface-induced scattering that enhances the quasi direct, zero-phonon transitions by mixing direct Gamma-like wave function character into the indirect X-like conduction band states, as well as from space confinement that broadens the distribution of wave functions in k-space. The absorption enhancement factor increases exponentially with decreasing NC size and is correlated with the exponentially increasing direct Gamma-like wave function character mixed into the NC conduction states. This observation and its theoretical understanding could lead to engineering of Si and other indirect band gap NC materials for optical and optoelectronic applications. PMID- 26898671 TI - An integrated index for automated detection of infarcted myocardium from cross sectional echocardiograms using texton-based features (Part 1). AB - Cross-sectional view echocardiography is an efficient non-invasive diagnostic tool for characterizing Myocardial Infarction (MI) and stages of expansion leading to heart failure. An automated computer-aided technique of cross sectional echocardiography feature assessment can aid clinicians in early and more reliable detection of MI patients before subsequent catastrophic post-MI medical conditions. Therefore, this paper proposes a novel Myocardial Infarction Index (MII) to discriminate infarcted and normal myocardium using features extracted from apical cross-sectional views of echocardiograms. The cross sectional view of normal and MI echocardiography images are represented as textons using Maximum Responses (MR8) filter banks. Fractal Dimension (FD), Higher-Order Statistics (HOS), Hu's moments, Gabor Transform features, Fuzzy Entropy (FEnt), Energy, Local binary Pattern (LBP), Renyi's Entropy (REnt), Shannon's Entropy (ShEnt), and Kapur's Entropy (KEnt) features are extracted from textons. These features are ranked using t-test and fuzzy Max-Relevancy and Min Redundancy (mRMR) ranking methods. Then, combinations of highly ranked features are used in the formulation and development of an integrated MII. This calculated novel MII is used to accurately and quickly detect infarcted myocardium by using one numerical value. Also, the highly ranked features are subjected to classification using different classifiers for the characterization of normal and MI LV ultrasound images using a minimum number of features. Our current technique is able to characterize MI with an average accuracy of 94.37%, sensitivity of 91.25% and specificity of 97.50% with 8 apical four chambers view features extracted from only single frame per patient making this a more reliable and accurate classification. PMID- 26898672 TI - Comment on: Anastomotic techniques in open Roux-en-Y gastric bypass: primary open surgery and converted procedures. PMID- 26898674 TI - Analysis of two Schistosoma mansoni uridine phosphorylases isoforms suggests the emergence of a protein with a non-canonical function. AB - Reports of Schistosoma mansoni strains resistant to praziquantel, the only therapeutic strategy available for the treatment of schistosomiasis, have motivated the scientific community towards the search for new possible therapies. Biochemical characterization of the parasite's metabolism is an essential component for the rational development of new therapeutic alternatives. One of the so far uncharacterized enzymes is uridine phosphorylase (UP) (EC 2.4.2.3), for which the parasite genome presents two isoforms (SmUPa and SmUPb) that share 92% sequence identity. In this paper, we present crystal structures for SmUPa and SmUPb in their free states as well as bound to different ligands. This we have complemented by enzyme kinetic characterization and phylogenetic analyses. Both enzymes present an overall fold and active site structure similar to other known UPs. The kinetic analyses showed conclusively that SmUPa is a regular uridine phosphorylase but by contrast SmUPb presented no detectable activity. This is particularly noteworthy given the high level of sequence identity between the two isoforms and is probably the result of the significant differences observed for SmUPb in the vicinity of the active site itself, suggesting that it is not a UP at all. On the other hand, it was not possible to identify an alternative function for SmUPb, although our phylogenetic analyses and expression data suggest that SmUPb is still functional and plays a role in parasite metabolism. The unusual UPb isoform may open up new opportunities for understanding unique features of S. mansoni metabolism. PMID- 26898673 TI - Hospital variation in rates of acid-reducing medication use after laparoscopic sleeve gastrectomy. AB - BACKGROUND: Postoperative gastroesophageal reflux is one of the most important long-term complications of sleeve gastrectomy, the most common bariatric procedure. OBJECTIVE: To assess variation in hospital performance with laparoscopic sleeve gastrectomy using rates of acid-reducing medication use at postoperative 1 year. SETTING: Clinical registry of bariatric surgical patients at academic and community hospitals in Michigan. METHODS: We studied 2923 patients who underwent laparoscopic sleeve gastrectomy across 39 hospitals in the Michigan Bariatric Surgery Collaborative, 2007 to 2014. We compared risk- and reliability-adjusted rates of new-onset reflux-defined by new use of acid reducing medication-across hospitals and in relation to surgical quality indicators (hospital procedure volume and 30-day complications). RESULTS: Overall, 20% of patients were newly taking acid-reducing medication at postoperative 1 year. Hospital rates of new medication use varied 3-fold, ranging from 10% (95% CI 7-15%) to 31% (95% CI 23-40%) of patients. Of the 2 hospitals with significantly lower rates of new medication use, 1 was high volume and 1 was medium volume. The 1 hospital with significantly higher rates was medium volume. Rates of acid-reducing medication use did not correlate with hospital volume or perioperative complications. CONCLUSION: Across Michigan hospitals, rates of new acid-reducing medication use at 1 year after laparoscopic sleeve gastrectomy varied widely and did not correlate with traditional quality indicators. Future research could explore differences in surgical technique to better understand the factors underlying variation in long-term outcomes after sleeve gastrectomy. PMID- 26898675 TI - Hypoxia-inducible factor-1alpha: A promising therapeutic target in endometriosis. AB - Endometriosis is a common gynecologic disease defined as the presence of ectopic endometrial tissues on the ovaries and pelvic peritoneum, and it is a significant cause of pelvic pain, dysmenorrhea and infertility of women in their reproductive age. However, the etiology of endometriosis remains obscure. In recent years, a growing body of evidence validated that hypoxia developed a close relationship with endometriosis and the expression of hypoxia-inducible factor-1alpha (HIF 1alpha) was increased significantly in the development of endometriosis. Furthermore, inhibiting the expression of HIF-1alpha contributed to suppress endometriosis progression, suggesting HIF-1alpha plays a critical function in endometriosis. Nevertheless, the mechanisms by which HIF-1alpha associates with endometriosis are still undefined. In this brief review, we had a general understanding of HIF-1alpha firstly, and then we tried to sum up the collective knowledge of HIF-1alpha in endometriosis. Finally, we will discuss kinds of novel therapeutic approaches to endometriosis based on the functions of HIF-1alpha. PMID- 26898676 TI - Response to "Facial Soft Tissue Thicknesses: Noise, Signal, and P" by Stephan, Munn and Caple. PMID- 26898677 TI - Accuracy of cut-off value by measurement of third molar index: Study of a Colombian sample. AB - The aim of this cross-sectional study was to test the accuracy of cut-off value of 0.08 by measurement of third molar index (I3M) in assessing legal adult age of 18 years in a sample of Colombian children and young adults. Digital orthopantomographs of 288 Colombian children and young adults (163 girls and 125 boys), aged between 13 and 22 years, were analysed. Concordance correlation coefficient (rhoc) and kappa statistics (Cohen's Kappa coefficient) showed that repeatability and reproducibility are high for both intra- and inter-observer error. kappa statistics for intra- and inter-observer agreement in decision on adult or minor was 0.913 and 0.877, respectively. Age distribution gradually decreases as I3M increases in both girls and boys. For girls, the sensitivity test was 95.1% (95% CI 87.1%-95%) and specificity was 93.8% (95% CI 87.1%-98.8%). The proportion of correctly classified individuals was 95.1%. For boys, the sensitivity test was 91.7% (95% CI 85.1%-96.8%) and specificity was 90.6% (95% CI 82.1%-97.8%). The proportion of correctly classified individuals was 89.7%. The cut-off value of 0.08 is highly useful to determine if a subject is 18 years of age or older or not. PMID- 26898678 TI - Iron-nitrogen-activated carbon as cathode catalyst to improve the power generation of single-chamber air-cathode microbial fuel cells. AB - In order to improve the performance of microbial fuel cell (MFC), iron-nitrogen activated carbon (Fe-N-C) as an excellent oxygen reduction reaction (ORR) catalyst was prepared here using commercial activated carbon (AC) as matrix and employed in single chamber MFC. In MFC, the maximum power density increased to 2437+/-55 mW m(-2), which was 2 times of that with AC. The open circuit potential (OCP) of Fe-N-C cathode (0.47) was much higher than that of AC cathode (0.21 V). The R0 of Fe-N-C decreased by 47% from 14.36 Omega (AC) to 7.6 Omega (Fe-N-C). From X-ray photoelectron spectroscopy (XPS), pyridinic nitrogen, quaternary nitrogen and iron species were present, which played an important role in the ORR performance of Fe-N-C. These results demonstrated that the as-prepared Fe-N-C material provided a potential alternative to Pt in AC air cathode MFC for relatively desirable energy generation and wastewater treatment. PMID- 26898679 TI - Recovery of carboxylic acids produced during dark fermentation of food waste by adsorption on Amberlite IRA-67 and activated carbon. AB - Amberlite IRA-67 and activated carbon were tested as promising candidates for carboxylic acid recovery by adsorption. Dark fermentation was performed without pH control and without addition of external inoculum at 37 degrees C in batch mode. Lactic, acetic and butyric acids, were obtained, after 7days of fermentation. The maximum acid removal, 74%, from the Amberlite IRA-67 and 63% from activated carbon was obtained from clarified fermentation broth using 200gadsorbent/Lbroth at pH 3.3. The pH has significant effect and pH below the carboxylic acids pKa showed to be beneficial for both the adsorbents. The un controlled pH fermentation creates acidic environment, aiding in adsorption by eliminating use of chemicals for efficient removal. This study proposes simple and easy valorization of waste to valuable chemicals. PMID- 26898680 TI - Impact of Genomic Counseling on Informed Decision-Making among ostensibly Healthy Individuals Seeking Personal Genome Sequencing: the HealthSeq Project. AB - Personal genome sequencing is increasingly utilized by healthy individuals for predispositional screening and other applications. However, little is known about the impact of 'genomic counseling' on informed decision-making in this context. Our primary aim was to compare measures of participants' informed decision-making before and after genomic counseling in the HealthSeq project, a longitudinal cohort study of individuals receiving personal results from whole genome sequencing (WGS). Our secondary aims were to assess the impact of the counseling on WGS knowledge and concerns, and to explore participants' satisfaction with the counseling. Questionnaires were administered to participants (n = 35) before and after their pre-test genomic counseling appointment. Informed decision-making was measured using the Decisional Conflict Scale (DCS) and the Satisfaction with Decision Scale (SDS). DCS scores decreased after genomic counseling (mean: 11.34 before vs. 5.94 after; z = -4.34, p < 0.001, r = 0.52), and SDS scores increased (mean: 27.91 vs. 29.06 respectively; z = 2.91, p = 0.004, r = 0.35). Satisfaction with counseling was high (mean (SD) = 26.91 (2.68), on a scale where 6 = low and 30 = high satisfaction). HealthSeq participants felt that their decision regarding receiving personal results from WGS was more informed after genomic counseling. Further research comparing the impact of different genomic counseling models is needed. PMID- 26898681 TI - Risk-reduction surgery in pediatric surgical oncology: A perspective. AB - OBJECTIVE: A small percentage of pediatric solid cancers arise as a result of clearly identified inherited predisposition syndromes and nongenetic lesions. Evidence supports preemptive surgery for children with genetic [multiple endocrine neoplasia type 2 (MEN2), familial adenomatous polyposis syndrome (FAP), hereditary nonpolyposis colorectal cancer (HNPCC), and hereditary diffuse gastric cancer (HDGC) and nongenetic [thyroglossal duct cysts (TGDC), congenital pulmonary airway malformations (CPAM), alimentary tract duplication cysts (ATDC), and congenital choledochal cysts (CCC)] developmental anomalies. Our aim was to explore the utility of risk reduction surgery to treat and prevent cancer in children. METHODS: A systematic review of the available peer-reviewed literature on PubMed was performed using a PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) search strategy, where possible. Search items included "risk reduction surgery", "hereditary cancer predisposition syndrome", "multiple endocrine neoplasia type 2", "familial adenomatous polyposis", "hereditary nonpolyposis colorectal cancer", "hereditary diffuse gastric cancer", "thyroglossal duct cysts", congenital pulmonary airway malformations", "alimentary tract duplication cysts", "malignant transformation", and "guidelines". RESULTS: We identified 67 articles that met the inclusion criteria describing the indications for prophylactic surgery in surgical oncology. For the genetic predisposition syndromes, 7 studies were related to professional endorsed guidelines, 7 were related to surgery for MEN2, 11 were related to colectomy for FAP, 6 were related to colectomy for HNPCC, and 12 related to gastrectomy for HDGC. Articles for the nongenetic lesions included 5 for techniques related to TGDC resection, 9 for surgery for CPAMs, and 10 for resection of ATDCs. Guidelines and strategies varied significantly especially related to the extent and timing of surgical intervention; the exception was for the timing of thyroidectomy in children with MEN2. CONCLUSION: Current evidence supporting prophylactic surgery in the management of pediatric cancer predisposition syndromes and nongenetic lesions is best delineated for thyroidectomy to prevent medullary thyroid cancer in children with MEN2 (Strength of Recommendation Grade B/C). Despite the lack of pediatric specific evidence-based recommendations regarding the appropriate extent and timing for risk-reduction surgery for FAP, HNPCC, HDGC and nongenetic anomalies, our review represents an opportunity towards understanding the postgenomic development of these lesions and provides current indications and techniques for preemptive cancer prevention surgery in children. PMID- 26898682 TI - Outcomes of minimally invasive parathyroidectomy in pediatric patients with primary hyperparathyroidism owing to parathyroid adenoma: A single institution experience. AB - BACKGROUND: Guidelines for treatment of primary hyperparathyroidism (PHPT) in young patients recommend surgery. Outcomes of minimally invasive parathyroidectomy (MIP) are well established in adults, but not in pediatric patients. OBJECTIVE: The objective of the study is to determine effectiveness of preoperative imaging and MIP aided by intraoperative PTH (ioPTH) measurement in children with primary hyperparathyroidism (PHPT). METHODS AND DESIGN: This is a retrospective chart review of diagnostic and follow-up data up to 12months post MIP of patients with PHPT who underwent parathyroidectomy at the Children's Hospital of Philadelphia between January 1, 2009 and March 31, 2015. RESULTS: Data were available for 16 of 17 patients age 8-17years (11 females, 6 males): 2 had ectopic intrathymic adenomas while 14 had eutopic adenomas. Fifteen patients had ioPTH, including 14 who underwent MIP, defined as a 2cm central neck incision. All patients with data at 6months postparathyroidectomy (13/16) showed normal PTH and calcium. Ultrasound and sestamibi scans had a combined sensitivity of 87.5%. CONCLUSIONS: MIP is an appropriate alternative to standard neck exploration in pediatric patients with PHPT with a single parathyroid adenoma. ioPTH is especially useful to confirm cure and limit surgical exploration when imaging studies are negative. Sestamibi scans and ultrasound are complementary studies. PMID- 26898683 TI - Cerebral Lactate Metabolism After Traumatic Brain Injury. AB - Cerebral energy dysfunction has emerged as an important determinant of prognosis following traumatic brain injury (TBI). A number of studies using cerebral microdialysis, positron emission tomography, and jugular bulb oximetry to explore cerebral metabolism in patients with TBI have demonstrated a critical decrease in the availability of the main energy substrate of brain cells (i.e., glucose). Energy dysfunction induces adaptations of cerebral metabolism that include the utilization of alternative energy resources that the brain constitutively has, such as lactate. Two decades of experimental and human investigations have convincingly shown that lactate stands as a major actor of cerebral metabolism. Glutamate-induced activation of glycolysis stimulates lactate production from glucose in astrocytes, with subsequent lactate transfer to neurons (astrocyte neuron lactate shuttle). Lactate is not only used as an extra energy substrate but also acts as a signaling molecule and regulator of systemic and brain glucose use in the cerebral circulation. In animal models of brain injury (e.g., TBI, stroke), supplementation with exogenous lactate exerts significant neuroprotection. Here, we summarize the main clinical studies showing the pivotal role of lactate and cerebral lactate metabolism after TBI. We also review pilot interventional studies that examined exogenous lactate supplementation in patients with TBI and found hypertonic lactate infusions had several beneficial properties on the injured brain, including decrease of brain edema, improvement of neuroenergetics via a "cerebral glucose-sparing effect," and increase of cerebral blood flow. Hypertonic lactate represents a promising area of therapeutic investigation; however, larger studies are needed to further examine mechanisms of action and impact on outcome. PMID- 26898684 TI - The Role of Vascular Imaging in the Initial Assessment of Patients with Acute Ischemic Stroke. AB - Over the last few years, improvement in radiological imaging and treatment has changed the management of acute ischemic stroke. We have made significant advances in not only the imaging modalities themselves but also in identifying imaging parameters that can help us predict patient outcomes with both intravascular thrombolysis and endovascular thrombectomy. In this review, we describe the added utility of baseline vascular imaging including computed tomography angiography and magnetic resonance angiography in the diagnosis and management of patients with acute ischemic stroke. We focus on information these imaging modalities provide on clot characteristics, tissue state, collateral status, and endovascular planning. We also highlight the benefits of newer imaging modalities like dynamic computed tomography angiography (CTA) and multi phase CTA. Lastly, we also describe some of the disadvantages of vascular imaging in ischemic stroke. PMID- 26898685 TI - Allergic Rhinitis and Chronic Daily Headaches: Is There a Link? AB - Allergic rhinitis and migraine remain on the list of the most common diseases affecting adults. Migraines and headaches due to allergic rhinitis are easily confused because the symptoms of both conditions often overlap. Both may occur with sinus headache, nasal congestion, and lacrimation and may worsen with weather changes and exposure to allergens. No precise clinical definition exists for what constitutes a sinus headache, which has always been a diagnostic dilemma. Contrary to popular belief, headache is not a typical symptom of rhinitis. Some studies have shown that up to 90 % of sinus headaches are actually migraines. Nevertheless, patients with self-diagnosed sinus headache self-treat or are treated by primary care physicians and/or otolaryngologists with medications for rhinosinusitis, ignoring the neurogenic causes of the symptoms when most of these patients fulfill diagnostic criteria for chronic migraine. Chronic migraine affects 2 % of the general population and has a significant socioeconomic impact on society, incurring health care costs and diminishing quality of life; therefore, the proper diagnosis and treatment of these headache patients should be a priority. PMID- 26898686 TI - Novel Approaches to Optimization of Levodopa Therapy for Parkinson's Disease. AB - Levodopa (LD) is the most effective medication to treat Parkinson's disease (PD). However, motor fluctuations and drug-induced dyskinesia compromise the long-term success of levodopa therapy in PD. These response complications are due, at least in part, to fluctuating LD plasma levels (as a result of erratic gastric emptying, variable jejunal absorption, and most importantly, the short half-life of LD) with standard levodopa formulations. Keeping levodopa concentrations as constant as possible is the target for improving the pharmacokinetics and developing new ways of LD administration. In this article, we review novel oral and non-oral LD formulations including the ones that have successfully completed phase 3 clinical trials and have come to market and ones that are still in earlier phases of clinical development. PMID- 26898687 TI - Serological and molecular investigation of porcine sapovirus infection in piglets in Xinjiang, China. AB - Porcine sapovirus (PoSaV) is one of the important pathogens that cause acute gastroenteritis in piglets. A survey on the infection and epidemic status of PoSaV in Xinjiang Province, Northwest China, was conducted in this study. We applied indirect viral protein 1 (VP1)-ELISA method to detect specific antibodies in 1218 serum samples of 3-month-old piglets collected from eight regions in Xinjiang during 2013-2014 and also detected PoSaV in 146 diarrhea stools of piglets in these eight regions using RT-PCR technology. The results showed that the PoSaV-serological positive rates in piglets in eight different regions in Xinjiang were between 32.82 and 47.06% with a mean rate of 37.68%. The average positive rate of PCR in stools of piglets was 3.42%. Sequencing and comparative analysis of five PCR-amplified DNA fragments revealed that four epidemic strains of PoSaV (swine/XJ-KO1, swine/XJ-AK2, swine/XJ-KS1, and swine/XJ-SHZ1) shared high nucleotide and amino acid identities with Cowden strain, while strain swine/XJ-AK1 shared higher high identities with Po/OH-JJ681/2000/US isolate. Phylogenetic clustering further verified that the epidemic strains of PoSaVs, i.e., swine/XJ-KO1, swine/XJ-AK2, swine/XJ-KS1, and swine/XJ-SHZ1, belong to genogroup (GIII) while swine/XJ-AK1 belongs to GVI. This survey confirmed for the first time that PoSaV infection was common in piglets in Xinjiang, China, and that the epidemic strains exist at least in both GIII and GVI clusters. This study provided the useful epidemiological data for scientific control and prevention of this disease. PMID- 26898688 TI - Nutritional and productive performance of dairy cows fed corn silage or sugarcane silage with or without additives. AB - The objective of this study was to compare the intake, digestibility, and performance of dairy cows fed corn silage, fresh sugarcane, and sugarcane ensiled in three different forms. Twenty-five Holstein cows at 114 +/- 12.6 days in milk (DIM) were used. A randomized block design was adopted, using an arrangement of repeated measures over time. The following treatments were tested: corn silage (CS); fresh sugarcane (FS); sugarcane silage without additives (SCS); sugarcane silage enriched with calcium oxide at 5 g/kg of forage (SCSc); and sugarcane silage enriched with Lactobacillus buchneri at 5 * 10(4) cfu/kg of forage (SCSb). The roughage to concentrate ratio was 60:40 for the CS diet and 40:60 for the sugarcane-based diets. The dry matter intake (DMI) as a function of body weight had a downward trend for the cows fed sugarcane silage, compared with those fed FS. The sugarcane silages had higher digestibilities of dry matter (DM), organic matter (OM), and neutral detergent fiber (NDFap), compared with FS. The use of L. buchneri or calcium oxide improved the diet's digestibility. The use of FS, sugarcane silage, or sugarcane silage with additives had no effects on milk and fat-corrected milk yield, compared to corn silage. Cows fed FS presented lower milk total solids content and had a downward trend for milk fat, compared with cows fed sugarcane-silage diets. Cows fed sugarcane silages produced milk with higher casein stability in the alcohol test than cows fed fresh-sugarcane diet. Sugarcane silage, with or without additives, did not reduce the intake of dairy cows, and the use of additives improved the fiber's digestibility. PMID- 26898689 TI - Cashew nut meal in the feeding of meat quails. AB - A study was aimed to evaluate the effects of cashew nut meal inclusion (CNM) on nutrient digestibility, performance and carcass characteristics of meat quails. A total of 432 meat quails with 7 days of age, were distributed in a completely randomized design with six treatments and nine replicates of eight birds each. Treatments were obtained with inclusion of CNM at levels of 0, 50, 100, 150, 200, and 250 g/kg. According to regression analysis, the inclusion of CNM, at levels above 50 g/kg, provided a linear reduction in digestibility of dry matter and metabolizable energy of diets, linear increase in feed intake and an increase in feed conversion ratio, not influencing weight gain and carcass characteristics. Comparing the results obtained with the different inclusion levels compared to those obtained with the diet without CNM (control group), it was noted that diets with 200 g/kg of CNM inclusion, the dry matter digestibility and metabolizable energy of diet were lower and the level of 250 g/kg provided higher feed intake. Considering the results, it can be inferred that cashew nut meal can be used as a feedstuff in meat quail's diets at levels up to 250 g/kg. PMID- 26898690 TI - Effects of inclusion levels of banana (Musa spp.) peelings on feed degradability and rumen environment of cattle fed basal elephant grass. AB - The effect of feeding varying banana peeling (BP) levels on rumen environment and feed degradation characteristics was evaluated using three rumen fistulated steers in four treatments. The steers were fed BP at 0, 20, 40, and 60% levels of the daily ration with basal elephant grass (EG) to constitute four diets. Maize bran, cotton seed cake, and Gliricidia sepium were offered to make the diets iso nitrogenous. The nylon bag technique was used to measure BP and EG dry matter (DM), crude protein (CP), and neutral detergent fiber (NDF) degradabilities at 0, 6, 12, 24, 48, 72, 96, and 120 h. Rumen fluid samples were collected to determine pH and volatile fatty acid (VFA) concentrations. Effective DM, CP, and NDF degradabilities of BP ranged between 574 and 807, 629-802, and 527-689 g/kg, respectively, being lower at higher BP levels. Elephant grass degradability behaved similarly with relatively high effective CP degradability (548-569 g/kg) but low effective DM and NDF degradability (381-403 and 336-373 g/kg, respectively). Rumen pH and VFA reduced with increasing BP in the diets. Rumen pH dropped to 5.8 and 5.9 at the 40 and 60% BP feeding levels, respectively. Banana peelings were better degraded than EG but higher BP levels negatively affected feed degradability and rumen environment. PMID- 26898691 TI - Rumen metabolism of swamp buffaloes fed rice straw supplemented with cassava hay and urea. AB - The objectives of this experiment were to investigate effects of cassava hay (CH) and urea (U) supplementation on feed intake, digestibility, rumen fermentation, and microbial protein synthesis of swamp buffaloes fed on rice straw. Four rumen fistulated swamp buffaloes, 365 +/- 15.0 kg, were randomly assigned according to a 4 * 4 Latin square design to receive four dietary treatments: T1 = CH 400 g/head/day + U 0 g/head/day, T2 = CH + U 30 g/head/day, T3 = CH + U 60 g/head/day, and T4 = CH + U 90 g/head/day, respectively. Results revealed that feed intake was not affected while nutrient digestibilities were increased (P < 0.05) with increasing U level supplementation especially at 90 g/head/day. Ruminal pH and temperature were not altered by urea supplementation, whereas ammonia nitrogen (NH3-N) and blood urea nitrogen were increased with urea supplement (P < 0.05). In addition, total volatile fatty acid and butyric acid were similar among treatments, while propionic acid (C3) was increased by level of urea supplement (P < 0.05), but acetic acid (C2) and C2/C3 ratio were significantly decreased (P < 0.05). On the other hand, protozoal population and methane production were decreased by CH and urea supplement, while bacterial population particularly those of proteolytic, cellulolytic, and amylolytic bacteria and efficiency of microbial nitrogen synthesis were linearly increased (P < 0.05). Based on this experiment, it suggested that supplementation of urea and cassava hay for buffaloes fed rice straw improved rumen ecology and increased fermentation end products and microbial protein synthesis while reducing protozoal populations and methane production. Urea supplements of 60-90 g/head/day when fed with cassava hay are recommended for swamp buffaloes consuming rice straw. PMID- 26898692 TI - Spatial epidemiological analysis of bovine encephalomyelitis outbreaks caused by Akabane virus infection in western Japan in 2011. AB - Akabane disease, which is distributed in temperate and tropical regions in the world, is a vector-borne disease of ruminants caused by the Akabane virus, transmitted by Culicoides biting midges. In 2011, outbreaks of Akabane viral encephalomyelitis occurred in the Shimane Prefecture in western Japan. In this study, a spatial epidemiological analysis was conducted to understand environmental factors associated with the spread of Akabane disease. By applying a conditional autoregressive model, the relationship between infection and environmental variables was explored. The results showed that the dominance of farmlands and the presence of infected farms within a 3-km radius had a significant effect on infection. This result implies that land use, which would relate with the vector habitat, and the presence of neighboring infected farms as a source of infection may have influenced the spread of the disease in this region. These findings provide basic insights into the spread of Akabane disease and useful suggestions for developing a surveillance program and preventive measures against the disease. PMID- 26898693 TI - Nutritional evaluation of ammoniated ensiled threshed sorghum top as a feed for goats. AB - Eighteen intact Red Sokoto male goats (15.4 +/- 0.68 kg BW) were used in a completely randomized design to evaluate the inclusion of urea-treated ensiled threshed sorghum top (UTST) in their diets. The inclusion rates of UTST were 0, 350 and 700 g/kg, replacing dried brewers' grains (DBG) by 0 (control) 50 and 100%, respectively. Intakes of dry matter, organic matter, total carbohydrate, hemicellulose, digestible nutrients and energy, nutrient digestibility, digestible organic matter fermented in the rumen, digestible organic matter, digestible energy/digestible crude protein (DCP) ratio, microbial protein synthesis, nitrogen retention and weight gain were lower (P < 0.05; 0.01) in 700 g/kg UTST than in 0 and 350 g/kg UTST. Intakes of crude protein, non-fibre carbohydrates and DCP, nitrogen balance and volatile fatty acid decreased (P < 0.01) with increasing level of UTST in the diets, but ruminal pH, NH3-N and total nitrogen increased (P < 0.01) with increasing rate of UTST. Feed/gain ratio and urinary nitrogen were higher (P < 0.01) for 700 g/kg UTST compared to 0 and 350 g/kg UTST. A dietary inclusion level of 350 g/kg UTST (replacing 50% of DBG) in the diet was the most suitable level for goats under the current experimental conditions. PMID- 26898694 TI - Novel SNP identification in exon 3 of HSP90AA1 gene and their association with heat tolerance traits in Karan Fries (Bos taurus * Bos indicus) cows under tropical climatic condition. AB - Heat shock proteins (HSPs) act as molecular chaperones those are preferentially transcribed in respose to heat stress and the polymorphism in HSP genes associated with heat tolerance traits in cows. HSP90AA1 gene has been mapped on Bos taurus autosome 21 (BTA-21) and spans nearly 5368 bp comprising of 11 exons out of which the first exon does not translate. The present study was done on Karan Fries (5/8 HF * 3/8 Tharparkar) cows reared in tropical climate with the objectives of identifying single-nucleotide polymorphisms (SNPs) in targeted regions (exon 3) of HSP90AA1 gene and analyzing their association with heat tolerance traits in Karan Fries cows. Respiration rate (RR) and rectal temperature (RT) were recorded once daily for four consecutive days during probable extreme hours in different seasons or temperature humidity index (THI), viz., winter, spring, and summer. For detecting single-nucleotide polymorphisms, sequence data were analyzed using BioEdit software (version 7.2). Comparative sequence analysis of HSP90AA1 gene showed point mutation, viz., g.1209A>G (exon 3) as compared to Bos taurus (NCBI Ref Seq: AC_000178.1). Association analysis indicated that THI was influenced (P < 0.01) by RR, RT, and HTC. Similarly, SNPs at locus g.1209A>G were categorized into three genotypes, i.e., AA, AG, and GG, and the least squares means (LSMEANS) of RR, RT, and HTC for GG (homozygous) genotype were significantly lower (P < 0.01) than AA (homozygous) and AG (heterozygous) genotypes. These findings may partly suggest that cows with GG genotypes were favored for heat tolerance trait, which can be used as an aid to selection for thermo-tolerance Karan Fries cows for better adaptation in subtropical and tropical hot climate. PMID- 26898696 TI - Letter to the editor. PMID- 26898695 TI - Effect of Bacteriophages on the Growth of Flavobacterium psychrophilum and Development of Phage-Resistant Strains. AB - The controlling effect of single and multiple phages on the density of Flavobacterium psychrophilum at different initial multiplicity of infection (MOI) was assessed in batch cultures to explore the potential for phage-based treatment of this important fish pathogen. A high initial phage concentration (MOI = 0.3-4) was crucial for efficient viral lysis, resulting in a 10(4)-10(5)-fold reduction of phage-sensitive cells (both single phages and phage cocktails), which was maintained throughout the incubation (>10 days). Following cell lysis, regrowth of phage-resistant strains was examined and resistant strains were isolated for further characterization. The application of a mathematical model allowed simulation of phage-host interactions and resistance development, confirming indications from strain isolations that phage-sensitive strains dominated the regrowing population (>99.8%) at low MOI and phage-resistant strains (>87.8%) dominated at high MOI. A cross-infectivity test covering 68 isolated strains and 22 phages resulted in 23 different host susceptibility patterns, with 20 of the isolates being resistant to all the applied phages. Eleven isolated strains with different susceptibility patterns had lower growth rates (0.093 to 0.31 h(-1)) than the host strain (0.33 h(-1)), while 10 of 14 examined strains had lost the ability to take up specific substrates as shown by BIOLOG profiles. Despite increased selection for phage resistance at high MOI, the results emphasize that high initial MOI is essential for fast and effective control of F. psychrophilum infection and suggest that the small populations of resistant clones had reduced competitive abilities relative to the sensitive ancestral strain. PMID- 26898697 TI - Effect of organic solvents and ultrasound on the removal of orthodontic brackets. AB - OBJECTIVE: To evaluate the effect of organic gel solvents (70% acetone and 90% ethanol) and ultrasound in the removal of metallic brackets. MATERIALS AND METHODS: Metallic brackets were bonded with light-cured orthodontic composite (Transbond XT) in 120 human bicuspids and divided into 6 groups for the enamel etch-and-rinse adhesive system (XT) and 6 groups to self-etching system (SEPT) according to pretreatment to removal test: control, 70% acetone, 90% ethanol, ultrasound, 70% acetone+ultrasound, and 90% ethanol+ultrasound. The brackets were subjected to removal by shear testing and Adhesive Remnant Index (ARI) evaluation. Some specimens were prepared and its adhesive interface and etching ability observed by scanning electron microscopy (SEM). RESULTS: Only the factor 'ultrasound' and its interaction with 'adhesive' were detected as a source of variance, with the SEPT/ultrasound showing the lowest shear strength than the other groups. Regardless the factor 'ultrasound', XT showed a higher ARI than SEPT; however, when the solvents were used, no differences were detected between XT and SEPT. CONCLUSION: The organic solvents were not effective in reducing shear bond strength. The etch-and-rinse adhesive system showed a higher and more favorable ARI score than the self-etching primer. The behavior of the organic solvents on ARI showed to be better when associated with the self-etching primer. The ultrasound was effective in reducing the shear bond strength of the self etching adhesive system but not in affecting the ARI of the adhesive systems. PMID- 26898698 TI - Stress symptoms among adolescents before and after scoliosis surgery: correlations with postoperative pain. AB - AIMS AND OBJECTIVES: The aim of this study was to describe stress symptoms among adolescents before and after scoliosis surgery and to explore correlations with postoperative pain. BACKGROUND: Scoliosis surgery is a major surgical procedure. Adolescent patients suffer from preoperative stress and severe postoperative pain. Previous studies indicate that there is a risk of traumatisation and psychological complications during the recovery period. DESIGN: A prospective quantitative cohort study with consecutive inclusion of participants. METHODS: A cohort of 37 adolescent patients aged 13-18. To assess the adolescents' experiences before surgery and at six to eight months after surgery, the Trauma Symptom Checklist for Children - Alternative version, Youth Self-Report and Kiddie Schedule for Affective Disorder and Schizophrenia for children 12-18 were used. The Visual Analogue Scale was used for self-report of postoperative pain on day three. RESULTS: Rates of anxiety/depression and internalising behaviour were significantly higher before surgery than six months after. Preoperative anger, social problems and attention problems correlated significantly with postoperative pain on day three. At follow-up, postoperative pain correlated significantly with anxiety, social problems and attention problems. CONCLUSIONS: The results of this study indicate a need for interventions to reduce perioperative stress and postoperative pain to improve the quality of nursing care. RELEVANCE TO CLINICAL PRACTICE: Attention to preoperative stress and implementation of interventions to decrease stress symptoms could ameliorate the perioperative process by reducing levels of postoperative pain, anxiety, social and attention problems in the recovery period. PMID- 26898699 TI - Peripherally Inserted Central Catheters (PICCs) in CKD: PICC'ing the Best Access for Kidney Disease Patients. PMID- 26898700 TI - Variability May Be the "Law of Life," but Blood Pressure Variability May Forebode a Shorter Life. PMID- 26898701 TI - Cochlear re-implantation: lessons learnt and the way ahead. AB - Conclusion A cochlear re-implantation procedure is undesirable; however, the cochlear implant surgeon may have to perform a re-implantation procedure occasionally for various reasons. Following standard techniques, implant performance comparable with primary implantation may be achieved. Objective To study the causes and outcomes of cochlear re-implantation in an Asian Indian population. Study design Retrospective analysis of clinical charts over an 18 year period with prospective follow-up of patients. Methods The charts of 534 patients, who underwent cochlear implant, at an Otorhinolaryngology institutional Centre, from January 1997 to January 2015 were studied. Of these, the charts of 18 patients who underwent cochlear re-implantation were studied. The causes and audiological and speech outcomes were analysed. Results Eighteen patients (3.4%) underwent cochlear re-implantation for various reasons. The commonest indication was device failure in seven patients (39%), followed by electrode extrusion in five (28%), trauma in three (11%), electrode migration in two (11%) and improper electrode placement in one (6%) patient. The audiological performance tests and speech tests either remained the same or improved from those achieved for patients undergoing primary implantation, in 87% patients. PMID- 26898702 TI - Biomimetic organization of collagen matrices to template bone-like microstructures. AB - The mineralized extracellular matrix (ECM) of bone is essential in vertebrates to provide structure, locomotion, and protect vital organs, while also acting as a calcium and phosphate reservoir to maintain homeostasis. Bone's structure comprises mainly structural collagen fibrils, hydroxyapatite nanocrystals and water, and it is the organization of the densely-packed collagen matrix that directs the organization of the mineral crystallites. Biogenic mineralization occurs when osteoblasts release "mineral bearing globules" which fuse into the preformed collagen matrix, and upon crystallization of this amorphous precursor, the fibrils become embedded with [001] oriented nanocrystals of hydroxyapatite. Our prior work has shown that this nanostructured organization of bone can be reproduced in vitro using the polymer-induced liquid-precursor (PILP) process. In this report, our focus is on using biomimetic processing to recreate both the nano- and micro-structure of lamellar bone. We first applied molecular crowding techniques to acidic, type-I collagen solutions to form dense, liquid crystalline collagen (LCC) scaffolds with cholesteric order. We subsequently mineralized these LCCs via the PILP process to achieve a high degree of intrafibrillar mineral, with compositions and organization similar to that of native bone and with a "lamellar" microstructure generated by the twisting LCC template. In depth characterization of the nano- and micro-structure was performed, including optical and electron microscopy, X-ray and electron diffraction, and thermogravimetric analyses. The results of this work lead us closer to our goal of developing hierarchically structured, collagen-hydroxyapatite composites which can serve as fully synthetic, bioresorbable, load-bearing bone substitutes that are remodeled by the native BRU. PMID- 26898703 TI - Asthma and atopic dermatitis in children born moderately and late preterm. AB - This national register study aimed to evaluate the need of asthma medication reimbursement and hospitalization due to asthma and atopic dermatitis up to 7 years of age in moderately preterm (MP) (32-33 weeks) and late preterm (LP) (34 36 weeks) children compared to very preterm (VP) (<32 weeks) and term (>=37 weeks) children. Altogether, 1,018,302 children born in Finland between 1991 and 2008 were assessed. The MP and LP groups received asthma medication reimbursement more frequently than term controls (8.0 and 5.7 vs. 3.8 %), but less frequently than VP children (15.4 %). Hospitalization due to asthma was more common among MP (10.6 %) and LP (7.3 %) children than term children (4.8 %) but less common than in VP children (20.1 %). Hospitalization due to atopic dermatitis was more frequent among term (5.2 %) compared to MP (4.2 %) and LP (4.7 %) children. Male sex, maternal smoking, maternal diabetes, and ventilator therapy predicted asthma medication in the MP and/or LP children. CONCLUSION: MP and LP children seem to need medication and hospitalization for asthma more often than term controls but less frequently than VP children followed by 7 years of age. Hospitalization due to atopic dermatitis becomes more common with increasing gestational age. WHAT IS KNOWN: * MP and LP infants have an increased risk for early respiratory morbidity and to asthma. * Less is known on the occurrence of atopic dermatitis in this patient group. What is New: * Medication and hospital care due to asthma were more frequent in school-aged MP and LP than in term infants. Male sex, maternal smoking, maternal diabetes and ventilator therapy predicted asthma. * Hospitalization due to atopic dermatitis became more common with increasing gestational age. PMID- 26898704 TI - The effect of red blood cell transfusion on the microcirculation of anemic children. AB - Red blood cell transfusion can improve but also might temporarily reduce the microcirculation. The buccal microcirculation was visualized and total vessel density (TVD) determined with sidestream dark field imaging in 19 pediatric anemic (Hb 7.2 g/dL, 95 % CI 6.5-7.9) oncology or hematology patients receiving red blood cell transfusions (Tx) and in 18 age-matched healthy non-anemic controls. After transfusion, Hb (8.0 g/dL, 95 % CI 7.3-8.6) and TVD increased (14.7 +/- 1.7 versus 16.6 +/- 2.0 mm/mm(2)) significantly with a concomitant decrease in RBC velocity in medium-sized vessels (pre-Tx 711 +/- 199 versus post Tx 627 +/- 163 MUm/s). Compared to the controls, pre-Tx TVD (17.5 +/- 1.3 mm/mm(2)) was lower and RBC velocity (476 +/- 77 MUm/s) was significantly higher. After transfusion, TVD and RBC velocity remained significantly lower and higher, respectively. In a subgroup, analysis of the transfused children with infection of TVD at baseline was lower with a larger increase after transfusion compared to anemic children without infection (DeltaTVD 3.4 +/- 2.6 versus DeltaTVD 1.3 +/- 1.5 mm/mm(2)). CONCLUSION: With the rise of hemoglobin after transfusion, significant improvements of tissue perfusion were demonstrated but differences to non-anemic controls persisted. In particular, the microcirculation of anemic oncology patients with infection improved after transfusion. WHAT IS KNOWN: * Transfusions can improve but also temporarily reduce the microcirculation. * In neonates, transfusion significantly increases total vessel density. What is New: * Pretransfusion, the microcirculation of the anemic children differed significantly from the controls. * After transfusion, the microcirculation improved but still differed from the controls. * These changes were most profound in anemic patients with concurrent infection, therefore transfusion threshholds might need to be higher. PMID- 26898705 TI - A new simple six-step model to promote recruitment to RCTs was developed and successfully implemented. AB - OBJECTIVES: How a randomized controlled trial (RCT) is explained to patients is a key determinant of recruitment to that trial. This study developed and implemented a simple six-step model to fully inform patients and to support them in deciding whether to take part or not. STUDY DESIGN AND SETTING: Ninety-two consultations with 60 new patients were recorded and analyzed during a pilot RCT comparing surgical and nonsurgical interventions for hip impingement. Recordings were analyzed using techniques of thematic analysis and focused conversation analysis. RESULTS: Early findings supported the development of a simple six-step model to provide a framework for good recruitment practice. Model steps are as follows: (1) explain the condition, (2) reassure patients about receiving treatment, (3) establish uncertainty, (4) explain the study purpose, (5) give a balanced view of treatments, and (6) Explain study procedures. There are also two elements throughout the consultation: (1) responding to patients' concerns and (2) showing confidence. The pilot study was successful, with 70% (n = 60) of patients approached across nine centers agreeing to take part in the RCT, so that the full-scale trial was funded. CONCLUSION: The six-step model provides a promising framework for successful recruitment to RCTs. Further testing of the model is now required. PMID- 26898706 TI - Opening-up the definition of systematic literature review: the plurality of worldviews, methodologies and methods for reviews and syntheses. PMID- 26898707 TI - Effect of roflumilast, novel phosphodiesterase-4 inhibitor, on lung chronic graft versus-host disease in mice. AB - Chronic graft-versus-host disease (CGVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation. Roflumilast has anti-inflammatory effects and has been used in the treatment of inflammatory airway diseases. It is at present unclear whether roflumilast may have a therapeutic role in CGVHD. To test this, we used the B10.D2 -> BALB/c model of CGVHD to address the therapeutic effect of roflumilast on the development of CGVHD. Lungs of animals treated with roflumilast exhibited less chronic inflammatory cell infiltration and fibrosis in the peribronchial and perivascular area versus allogeneic controls. To define the mechanism, we examined the expression of pro-inflammatory and profibrotic cytokines in the lung. Messenger RNA expression of interleukin-6 and interleukin 1beta in the lungs was significantly reduced in recipients treated with roflumilast. Similar changes were observed in profibrotic cytokines and chemokines. In addition, the percentage of Foxp3(+) regulatory T cells (Tregs), which have the potential to attenuate GVHD, increased significantly within the CD4(+) T cells with roflumilast in the lungs. In conclusion, roflumilast treatment attenuated murine lung CGVHD by blocking T-cell activation mediated by Tregs and downregulating pro-inflammatory and profibrotic cytokines, resulting in the reduction of lung inflammation and fibrosis. PMID- 26898708 TI - Chemosensitizing AML cells by targeting bone marrow endothelial cells. AB - Refractory disease is the greatest challenge in treating patients with acute myeloid leukemia (AML). Blood vessels may serve as sanctuary sites for AML. When AML cells were co-cultured with bone marrow endothelial cells (BMECs), a greater proportion of leukemia cells were in G0/G1. This led us to a strategy of targeting BMECs with tubulin-binding combretastatins, causing BMECs to lose their flat phenotype, degrade their cytoskeleton, cease growth, and impair migration despite unchanged BMEC viability and metabolism. Combretastatins also caused downregulation of BMEC adhesion molecules known to tether AML cells, including vascular cell adhesion molecule (VCAM)-1 and vascular endothelial (VE)-cadherin. When AML-BMEC co-cultures were treated with combretastatins, a significantly greater proportion of AML cells dislodged from BMECs and entered the G2/M cell cycle, suggesting enhanced susceptibility to cell cycle agents. Indeed, the combination of combretastatins and cytotoxic chemotherapy enhanced additive AML cell death. In vivo mice xenograft studies confirmed this finding by revealing complete AML regression after treatment with combretastatins and cytotoxic chemotherapy. Beyond highlighting the pathologic role of BMECs in the leukemia microenvironment as a protective reservoir of disease, these results support a new strategy for using vascular-targeting combretastatins in combination with cytotoxic chemotherapy to treat AML. PMID- 26898709 TI - Modulation of E-cadherin expression promotes migration ability of esophageal cancer cells. AB - Losing the E-cadherin plays an important role in the metastasis of cancer. The regulation of the expression of E-cadherin is unclear. Circadian rhythm alteration is associated with the pathogenesis of a number of cancers. This study aims to investigate the role of one of the circadian proteins, period-2 (Per2) in repressing the expression of E-cadherin in esophageal cancer (esophageal cancer). We observed that the levels of circadian protein Per2 were significantly increased and E-cadherin was significantly decreased in the tissue of human esophageal cancer with metastasis as compared with non-metastatic esophageal cancer. Overexpression of Per2 in the esophageal cancer cells markedly repressed the expression of E-cadherin. The pHDAC1 was detected in human esophageal cancer with metastasis, which was much less in the esophageal cancer tissue without metastasis. Overexpression of Per2 increased the levels of pHDAC1 as well as the E-cadherin repressors at the E-cadherin promoter locus. Overexpression of Per2 markedly increased the migratory capacity of esophageal cancer cells, which was abolished by the inhibition of HDAC1. We conclude that Per-2 plays an important role in the esophageal cancer cell metastasis, which may be a novel therapeutic target for the treatment of esophageal cancer. PMID- 26898711 TI - TPhP exposure disturbs carbohydrate metabolism, lipid metabolism, and the DNA damage repair system in zebrafish liver. AB - Triphenyl phosphate is a high production volume organophosphate flame retardant that has been detected in multiple environmental media at increasing concentrations. The environmental and health risks of triphenyl phosphate have drawn attention because of the multiplex toxicity of this chemical compound. However, few studies have paid close attention to the impacts of triphenyl phosphate on liver metabolism. We investigated hepatic histopathological, metabolomic and transcriptomic responses of zebrafish after exposure to 0.050 mg/L and 0.300 mg/L triphenyl phosphate for 7 days. Metabolomic analysis revealed significant changes in the contents of glucose, UDP-glucose, lactate, succinate, fumarate, choline, acetylcarnitine, and several fatty acids. Transcriptomic analysis revealed that related pathways, such as the glycosphingolipid biosynthesis, PPAR signaling pathway and fatty acid elongation, were significantly affected. These results suggest that triphenyl phosphate exposure markedly disturbs hepatic carbohydrate and lipid metabolism in zebrafish. Moreover, DNA replication, the cell cycle, and non-homologous end-joining and base excision repair were strongly affected, thus indicating that triphenyl phosphate hinders the DNA damage repair system in zebrafish liver cells. The present study provides a systematic analysis of the triphenyl phosphate-induced toxic effects in zebrafish liver and demonstrates that low concentrations of triphenyl phosphate affect normal metabolism and cell cycle. PMID- 26898712 TI - Toward the identification of neuroprotective agents: g-scale synthesis, pharmacokinetic evaluation and CNS distribution of (R)-RC-33, a promising SIGMA1 receptor agonist. AB - AIM: Nowadays, there is a great interest in the therapeutic potential of sigma1 receptor ligands for treating different CNS pathologies. Our previous investigations led to identify (R)-RC-33 as a potent and selective S1R agonist. RESULTS: Herein, we report the gram-scale synthesis, pharmacokinetic profile and CNS distribution of (R)-RC-33 in the mouse to determine the most suitable dosage schedule for in vivo administration. For comparative purposes, the same experiments were also performed with PRE-084, the most widely used S1R agonist commonly in pharmacological experiments. DISCUSSION: (R)-RC-33 shows a similar pharmacokinetic profile and a better CNS distribution when compared with PRE-084. CONCLUSION: (R)-RC-33 may be a promising candidate for in vivo studies in animal models of neurodegenerative diseases. PMID- 26898710 TI - Integrative topological analysis of mass spectrometry data reveals molecular features with clinical relevance in esophageal squamous cell carcinoma. AB - Combining MS-based proteomic data with network and topological features of such network would identify more clinically relevant molecules and meaningfully expand the repertoire of proteins derived from MS analysis. The integrative topological indexes representing 95.96% information of seven individual topological measures of node proteins were calculated within a protein-protein interaction (PPI) network, built using 244 differentially expressed proteins (DEPs) identified by iTRAQ 2D-LC-MS/MS. Compared with DEPs, differentially expressed genes (DEGs) and comprehensive features (CFs), structurally dominant nodes (SDNs) based on integrative topological index distribution produced comparable classification performance in three different clinical settings using five independent gene expression data sets. The signature molecules of SDN-based classifier for distinction of early from late clinical TNM stages were enriched in biological traits of protein synthesis, intracellular localization and ribosome biogenesis, which suggests that ribosome biogenesis represents a promising therapeutic target for treating ESCC. In addition, ITGB1 expression selected exclusively by integrative topological measures correlated with clinical stages and prognosis, which was further validated with two independent cohorts of ESCC samples. Thus the integrative topological analysis of PPI networks proposed in this study provides an alternative approach to identify potential biomarkers and therapeutic targets from MS/MS data with functional insights in ESCC. PMID- 26898713 TI - On the vibrational behavior of single- and double-walled carbon nanotubes under the physical adsorption of biomolecules in the aqueous environment: a molecular dynamics study. AB - The adsorption of biomolecules on the walls of carbon nanotubes (CNTs) in an aqueous environment is of great importance in the field of nanobiotechnology. In this study, molecular dynamics (MD) simulations were performed to understand the mechanical vibrational behavior of single- and double-walled carbon nanotubes (SWCNTs and DWCNTs) under the physical adsorption of four important biomolecules (L-alanine, guanine, thymine, and uracil) in vacuum and an aqueous environment. It was observed that the natural frequencies of these CNTs in vacuum reduce under the physical adsorption of biomolecules. In the aqueous environment, the natural frequency of each pure CNT decreased as compared to its natural frequency in vacuum. It was also found that the frequency shift for functionalized CNTs as compared to pure CNTs in the aqueous environment was dependent on the radius and the number of walls of the CNT, and could be positive or negative. PMID- 26898716 TI - Bodily maps of emotions across child development. AB - Different basic emotions (anger, fear, disgust, happiness, sadness, and surprise) are consistently associated with distinct bodily sensation maps, which may underlie subjectively felt emotions. Here we investigated the development of bodily sensations associated with basic emotions in 6- to 17-year-old children and adolescents (n = 331). Children as young as 6 years of age associated statistically discernible, discrete patterns of bodily sensations with happiness, fear, and surprise, as well as with emotional neutrality. The bodily sensation maps changed from less to more specific, adult-like patterns as a function of age. We conclude that emotion-related bodily sensations become increasingly discrete over child development. Developing awareness of their emotion-related bodily sensations may shape the way children perceive, label, and interpret emotions. PMID- 26898715 TI - Reliability and Validity of an Observational Measure of Client Decision-Making: The Client Language Assessment - Proximal/Distal (CLA-PD). AB - OVERVIEW: The Client Language Assessment - Proximal/Distal (CLA-PD) is a language rating system for measuring client decision-making in interventions that target a specified behavior change (e.g., alcohol or other drug use). In the CLA-PD, there are five dimensions of change language (Reason, Ability, Commitment, Taking Steps, Other) adapted from the client portion of the Motivational Interviewing Skill Code (MISC). For the CLA-PD, language codes are sub-divided to discriminate statements regarding the primary, or target behavior change (distal change) from the intermediate coping activities (proximal change) that are prescribed to facilitate that target behavior change. The goal of the CLA-PD is to allow for higher specificity than existing client language measures, when process studies consider interventions that are multi-session and skill-based (e.g., cognitive behavioral therapy). METHOD: Three raters received 40 hours of training on the use of the CLA-PD. The data were a sample of therapy session audio-files from a completed clinical trial (N=126), which enabled examination of client language across four sessions (i.e., first three and final attended) of three evidence based alcohol interventions (cognitive behavioral therapy, twelve-step facilitation therapy, motivational enhancement therapy). RESULTS: Inter-rater reliability results for summary scores showed "excellent" reliability for the measure. Specifically, two-way mixed intraclass coefficients ranged from .83 to .95. Internal consistency reliability showed alphas across sessions that ranged from "fair" to "good" (alpha=.74-.84). In convergent and discriminant validity analyses using data independently measured with MISC-based ratings, the pattern of results was as would be expected. Specifically, convergent correlations, by valence (i.e., change and sustain talk), between CLA-PD Distal and MISC-based language scores were moderate (r=.46-.55, p<.001) while discriminant correlations by valence for CLA-PD Proximal and MISC-based language scores were small (r=.22 .24, p<.05). Finally, proportion Change Talk Proximal predicted subsequent session coping behaviors (i.e., processes of change) as well as 3-month Alcoholics Anonymous involvement and attendance (ps<.05-.005), but not 3-month alcohol abstinence self-efficacy. Further, analyses of criterion predictive validity showed that proportion Change Talk Distal predicted 3- and 12-month drinking frequency and quantity measures (ps<.05-.005). CONCLUSIONS: When behavior change treatments are multi-session and/or skill-based, the present analyses suggest the CLA-PD is a promising, psychometrically sound observational rating measure of client verbalized decision-making. PMID- 26898714 TI - Allergic lung inflammation promotes atherosclerosis in apolipoprotein E-deficient mice. AB - Inflammation drives asthma and atherosclerosis. Clinical studies suggest that asthmatic patients have a high risk of atherosclerosis. Yet this hypothesis remains uncertain, given that Th2 imbalance causes asthma whereas Th1 immunity promotes atherosclerosis. In this study, chronic allergic lung inflammation (ALI) was induced in mice by ovalbumin sensitization and challenge. Acute ALI was induced in mice by ovalbumin and aluminum sensitization and ovalbumin challenge. Atherosclerosis was produced in apolipoprotein E-deficient (Apoe(-/-)) mice with a Western diet. When chronic ALI and atherosclerosis were produced simultaneously, ALI increased atherosclerotic lesion size, lesion inflammatory cell content, elastin fragmentation, smooth muscle cell (SMC) loss, lesion cell proliferation, and apoptosis. Production of acute ALI before atherogenesis did not affect lesion size, but increased atherosclerotic lesion CD4(+) T cells, lesion SMC loss, angiogenesis, and apoptosis. Production of acute ALI after atherogenesis also did not change atherosclerotic lesion area, but increased lesion elastin fragmentation, cell proliferation, and apoptosis. In mice with chronic ALI and diet-induced atherosclerosis, daily inhalation of a mast cell inhibitor or corticosteroid significantly reduced atherosclerotic lesion T-cell and mast cell contents, SMC loss, angiogenesis, and cell proliferation and apoptosis, although these drugs did not affect lesion area, compared with those that received vehicle treatment. In conclusion, both chronic and acute ALI promote atherogenesis or aortic lesion pathology, regardless whether ALI occurred before, after, or at the same time as atherogenesis. Antiasthmatic medication can efficiently mitigate atherosclerotic lesion pathology. PMID- 26898717 TI - CT-generated radiographs in patients with pelvic ring injury: can they be used in lieu of plain radiographs? AB - BACKGROUND: Pelvic ring injury classification traditionally is made using plain radiographs. Recent studies suggest that computed tomography (CT)-generated images have higher diagnostic accuracy than plain films for the classification of acetabular fractures. However, similar studies have not been performed for pelvic ring injuries. The purpose of this study was to compare CT-generated and plain radiographs in terms of the ability of surgeons at different experience levels to identify pelvic injury type. METHODS: CT-generated and plain radiograph image sets were created from 15 pelvic ring injury patients with known classification morphology. Three groups, each consisting of three orthopaedic surgeons representing different levels of expertise, viewed these image sets and recorded their diagnoses. These diagnoses were compared to the gold standard findings of the treating physician and to each other. RESULTS: Overall, there was a significantly improved ability to correctly classify pelvic ring injury type by CT-generated radiographs as compared to plain radiographs (p < 0.01). However, analysis of the groups revealed that this difference was limited to the less experienced groups (p < 0.05). CONCLUSIONS: CT-generated radiographs are diagnostically beneficial for less experienced surgeons and at least as good as conventional plain radiographs for experienced surgeons in classifying pelvic ring injuries. Therefore, CT-generated radiographs may be clinically valuable: sparing the patient additional radiation exposure and discomfort by avoiding the reordering of plain radiographs when the initial studies are of poor quality, as well as serving as a possible alternative for supplemental initial injury plain radiographic views. PMID- 26898719 TI - Understanding the contribution of hydroxyl to the energy band of a semiconductor: Bi2O(OH)2SO4vs. Bi6S2O15. AB - It is still a big challenge to facilely tune the energy bands of a semiconductor. Herein, we have mainly investigated energy bands and photochemical properties of Bi6S2O15 and Bi2O(OH)2SO4, which have very similar layered structures. It is found that the hydroxyls have down shifted the conduction band (CB, 0.21 eV) and valence band (VB, 4.39 eV) of Bi2O(OH)2SO4, compared with those (CB = 0 eV; VB = 3.36 eV) of Bi6S2O15. Moreover, the main oxidative species of Bi6S2O5 and Bi2O(OH)2SO4 are holes (h(+)) and hydroxyl radicals (OH) for the degradation of rhodamine B (RhB) dye, respectively. This obvious difference has been mainly attributed to the hydroxyls, which have changed the energy band structure and the band gap. In addition, we have also investigated the morphology-dependent properties of Bi2O(OH)2SO4. Under ultraviolet light irradiation (lambda <= 420 nm), Bi2O(OH)2SO4 microspheres show an activity 1.3 times and 2.2 times higher than the long flakes and straw sheaves for the degradation of (RhB), respectively. This study provides us a new idea that we can facilely tune the energy band of a semiconductor by introducing or removing hydroxyl or other anions. PMID- 26898718 TI - Meta-analysis of the risk of small bowel obstruction following open or laparoscopic colorectal surgery. AB - BACKGROUND: One of the potential advantages of laparoscopic compared with open colorectal surgery is a reduction in postoperative bowel obstruction events. Early reports support this proposal, but accumulated evidence is lacking. METHODS: A systematic review and meta-analysis was performed of randomized clinical trials and observational studies by searching the PubMed and Cochrane Library databases from 1990 to August 2015. The primary outcomes were early and late postoperative bowel obstruction following laparoscopic and open colorectal surgery. Both ileus and bowel obstruction were defined as a postoperative bowel obstruction. Subgroup and sensitivity analyses were performed, and a random effects model was used to account for the heterogeneity among the studies. RESULTS: Twenty-four randomized clinical trials and 88 observational studies were included in the meta-analysis; 106 studies reported early outcome and 12 late outcome. Collectively, these studies reported on the outcomes of 148 392 patients, of whom 58 133 had laparoscopic surgery and 90 259 open surgery. Compared with open surgery, laparoscopic surgery was associated with reduced rates of early (odds ratio 0.62, 95 per cent c.i. 0.54 to 0.72; P < 0.001) and late (odds ratio 0.61, 0.41 to 0.92; P = 0.019) postoperative bowel obstruction. Weighted mean values for early postoperative bowel obstruction were 8 (95 per cent c.i. 6 to 10) and 5 (3 to 7) per cent for open and laparoscopic surgery respectively, and for late bowel obstruction were 4 (2 to 6) and 3 (1 to 5) per cent respectively. CONCLUSION: The reduction in postoperative bowel obstruction demonstrates an advantage of laparoscopic surgery in patients with colorectal disease. PMID- 26898721 TI - X-ray structure of a lectin-bound DNA duplex containing an unnatural phenanthrenyl pair. AB - DNA duplexes containing unnatural base-pair surrogates are attractive biomolecular nanomaterials with potentially beneficial photophysical or electronic properties. Herein we report the first X-ray structure of a duplex containing a phen-pair in the center of the double helix in a zipper like stacking arrangement. PMID- 26898720 TI - Adherence to recommendations on lipid-based nutrient supplement and iron and folic acid tablet consumption among pregnant and lactating women participating in a community health programme in northwest Bangladesh. AB - Limited knowledge exists on sustained adherence to small-quantity lipid-based nutrient supplements for pregnant and lactating women (LNS-PL) and how this compares with that of other prenatal supplements. To address these gaps, a random subsample of women (n = 360) during pregnancy, early (6- to 12-week post-partum) and late (12- to 24-week post-partum) lactation, from an ongoing effectiveness trial in Bangladesh, was selected for in-home interviews about LNS-PL or iron/folic acid (IFA) use and preferences. Prevalence of high adherence (>=70% of the recommendation) based on self-reported supplement consumption was 67%, 68% and 81% among LNS-PL recipients during pregnancy, early and late lactation, and was 87% and 71% among IFA recipients during pregnancy and early lactation, respectively (P = 0.044). Programmatic factors (e.g. distribution and visits by programme staff) were consistently statistically significantly associated with reported high adherence. Among LNS-PL recipients, high overall supplement acceptability score [odds ratio (OR): 8.62; 95% confidence interval (CI) 3.53, 20.83] and use of reminder techniques (OR: 4.41; 95%CI 1.65, 11.76) were positively associated, and reported vomiting at enrollment was negatively associated (OR: 0.34; 95%CI 0.14, 0.80), with reported high adherence. Selected women (n = 16) and key informants (n = 18) participated in in-depth interviews about perceptions and acceptability of LNS-PL. Women perceived benefits of taking LNS-PL, but some faced barriers to consumption including aversion to odour and taste during pregnancy, forgetfulness and disruptions in supply. To achieve high adherence, results from this study suggest that maternal supplementation programmes should focus on programmatic barriers and consider incorporating reminder techniques. Organoleptic acceptability of LNS-PL, particularly during pregnancy, may also need to be addressed. PMID- 26898722 TI - A prototype of injector to control and to detect the release of magnetic beads within the constraints of multibifurcation magnetic resonance navigation procedures. AB - PURPOSE: An injector equipped with a bead capture and a bead detection system is presented. In the context of magnetic resonance navigation (MRN), in which MRI gradients are used to steer intravascular therapeutic carriers, fast and reliable injection is essential. In this paper, we present a prototype of injector to control and to detect the release of magnetic beads. METHODS: The injector relies on two distinct subsystems: (1) the capture subsystem, which creates local magnetic force to stop the flow of magnetic beads; and (2) the detection subsystem, which detects flowing beads and generates a trigger signal to start MRI gradient pulses. Both systems rely on small microcoils wound on the tubing. RESULTS: Five-turn microcoils show the best compromise between size and performance. Less than 5 mW of power is required to capture 0.8-mm beads moving in a flow above 5 mL min-1 or when a gradient above 200 mT m-1 is applied. The detection system is not sensitive to noise and detects every 0.8-mm bead in flow rates up to 14 mL m-1 . CONCLUSION: The prototype of injector shows performance above the requirements inherent to magnetic resonance navigation. This system is a step toward in vivo multibifurcation MRN. Magn Reson Med 77:444-452, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 26898723 TI - Effect of surface modifications on the bond strength of zirconia ceramic with resin cement resin. AB - OBJECTIVES: Purpose of this in vitro study was to evaluate the effect of surface modifications on the tensile bond strength between zirconia ceramic and resin. METHODS: Zirconia ceramic surfaces were treated with 150-MUm abrasive alumina particles, 150-MUm abrasive zirconia particles, argon-ion bombardment, gas plasma, and piranha solution (H2SO4:H2O2=3:1). In addition, slip casting surfaces were examined. Untreated surfaces were used as the control group. Tensile bond strengths (TBS) were measured after water storage for 3 days or 150 days with additional 37,500 thermal cycling for artificial aging. Statistical analyses were performed with 1-way and 3-way ANOVA, followed by comparison of means with the Tukey HSD test. RESULTS: After storage in distilled water for three days at 37 degrees C, the highest mean tensile bond strengths (TBS) were observed for zirconia ceramic surfaces abraded with 150-MUm abrasive alumina particles (TBS(AAP)=37.3 MPa, TBS(CAAP)=40.4 MPa), and 150-MUm abrasive zirconia particles (TBS(AZP)=34.8 MPa, TBS(CAZP)=35.8 MPa). Also a high TBS was observed for specimens treated with argon-ion bombardment (TBS(BAI)=37.8 MPa). After 150 days of storage, specimens abraded with 150-MUm abrasive alumina particles and 150-MUm abrasive zirconia particles revealed high TBS (TBS(AAP)=37.6 MPa, TBS(CAAP)=33.0 MPa, TBS(AZP)=22.1 MPa and TBS(CAZP)=22.8 MPa). A high TBS was observed also for specimens prepared with slip casting (TBS(SC)=30.0 MPa). A decrease of TBS was observed for control specimens (TBS(UNT)=12.5 MPa, TBS(CUNT)=9.0 MPa), specimens treated with argon-ion bombardment (TBS(BAI)=10.3 MPa) and gas plasma (TBS(GP)=11.0 MPa). A decrease of TBS was observed also for specimens treated with piranha solution (TBS(PS)=3.9 MPa, TBS(CPS)=4.1 MPa). A significant difference in TBS after three days storage was observed for specimens treated with different methods (p<0.001). Thermal cycling significantly reduced TBS for all groups (p<0.001) excluding groups: AAP(p>0.05), CAAP(p>0.05) and SC(p>0.05). However, the failure patterns of debonded specimens prepared with 150-MUm abrasive zirconia particles were 96.7% cohesive. CONCLUSION: Treatment of zirconia ceramic surfaces with abrasive zirconia particles is a promising method to increase the tensile bond strength without significant damage of the ceramic surface itself. An alternative promising method is slip casting. PMID- 26898724 TI - Multiple synchronous ventricular lipomas. PMID- 26898725 TI - Early ant trajectories: spatial behaviour before behaviourism. AB - In the beginning of the twentieth century, when Jacques Loeb's and John Watson's mechanistic view of life started to dominate animal physiology and behavioural biology, several scientists with different academic backgrounds got engaged in studying the wayfinding behaviour of ants. Largely unaffected by the scientific spirit of the time, they worked independently of each other in different countries: in Algeria, Tunisia, Spain, Switzerland and the United States of America. In the current literature on spatial cognition these early ant researchers--Victor Cornetz, Felix Santschi, Charles Turner and Rudolf Brun--are barely mentioned. Moreover, it is virtually unknown that the great neuroanatomist Santiago Ramon y Cajal had also worked on spatial orientation in ants. This general neglect is certainly due to the fact that nearly all these ant researchers were scientific loners, who did their idiosyncratic investigations outside the realm of comparative physiology, neurobiology and the behavioural sciences of the time, and published their results in French, German, and Spanish at rather inaccessible places. Even though one might argue that much of their work resulted in mainly anecdotal evidence, the conceptual approaches of these early ant researchers preempt much of the present-day discussions on spatial representation in animals. PMID- 26898726 TI - Effects of spirotetramat treatments on fecundity and carboxylesterase expression of Aphis gossypii Glover. AB - Spirotetramat is a novel tetramic acid-based insecticide, belonging to keto-enol pesticide family, with a novel mode of action; it interferes with lipid biosynthesis. Its insecticide activity against various agricultural pest insects have been demonstrated (e.g. on Myzus persicae, Bemisia tabaci and Tetranychus urticae). However, information available is currently limited on the efficacy of spirotetramat on the cotton aphid, Aphis gossypii, a key cotton pest worldwide. We assessed the spirotetramat toxicity on A. gossypii and evaluated its effects on aphid fecundity when exposed to a sublethal concentration (LC10) and to increasing lethal concentrations (LC25, LC50, and LC75). A key mechanism involved in insecticide resistance in aphids relates to esterase activity. We estimated the CarE activity and a CarE gene expression in aphids in response to spirotetramat exposure, then we tested tolerance of offspring to spirotetramat when the parents were exposed to the highest concentration tested in our study (LC75). Results showed that spirotetramat showed increasing toxicity to A. gossypii with exposure duration to treated leaves; LC50 ranged from 23,675.68 to 12.27 mg/L for 1 to 5-days exposure. In addition, spirotetramat reduced aphid daily fecundity, in all concentration treatments, especially with up to 90 % reduction in case of exposure to LC75. Total CarE activity increased dramatically and CarE mRNA expression was also up regulated in aphids after exposure to LC75 spirotetramat. Finally, the tolerance to spirotetramat in offspring (when parents were exposed to the LC75) showed a 2.5-fold increase when compared to control aphids. Consequently, spiroteramat showed potential for pest management of cotton aphids owing to both lethal and sublethal activities, notably strong impact on aphid fecundity. However, we also demonstrated that increased tolerance of A. gossypii to spirotetramat may happen through increased CarE- activity and subsequent metabolic degradation of the insecticide in aphids' body. PMID- 26898727 TI - Legalizing marijuana. PMID- 26898728 TI - Treating comorbid premenstrual dysphoric disorder in women with bipolar disorder. PMID- 26898729 TI - Smoking as a confounder of the association of suicidality with serum lipid levels. PMID- 26898730 TI - Smoking as a confounder of the association of suicidality with serum lipid levels -Author Response. PMID- 26898731 TI - Helicobacter pylori infection is associated with a reduced risk of developing eosinophilic oesophagitis. AB - BACKGROUND: Eosinophilic oesophagitis (EoE) represents a chronic immune-antigen mediated allergic disease of the oesophagus of still unknown aetiology. Environmental exposure has been postulated to play a pathogenetic role. Helicobacter pylori (H. pylori) infection has been inversely associated with allergic diseases including atopic dermatitis, asthma and allergic rhinitis and H. pylori may play a protective role in these conditions. Little is known about the relationship between EoE and H. pylori. AIM: To investigate in a case-control study whether H. pylori infection is associated with a reduced risk of developing EoE. METHODS: H. pylori infection was evaluated by serology in 58 [11(19%) female, 47 (81%) male, median age: 36.5 years, range 20-72 years] patients with a clinical and histologically proven diagnosis of EoE and 116 age and sex-matched controls (1 case: 2 controls). Antibodies against H. pylori were identified by enzyme-linked immunosorbent assay. Patients with H. pylori-specific IgG >= 30 enzyme immunounits were classified as H. pylori-positive. RESULTS: 3/58 (5.2%) patients with EoE had serological evidence of H. pylori infection (EoE - H. pylori current infection) and 5/58 (8.6%) reported prior eradication therapy for H. pylori infection (EoE - H. pylori former infection). The control group demonstrated significantly higher seroprevalence of H. pylori (37.9%, P < 0.0001) when compared to patients with EoE. EoE was inversely associated with H. pylori infection [odds ratio (OR) 0.24, 95% confidence interval (CI) 0.11-0.50]. CONCLUSION: Helicobacter pylori infection is inversely associated with EoE. Our results may contribute to further understanding the pathogenesis and evolving aetiology of EoE. PMID- 26898732 TI - Clinically assessed posttraumatic stress in patients with breast cancer during the first year after diagnosis in the prospective, longitudinal, controlled COGNICARES study. AB - OBJECTIVE: There is ongoing debate whether cancer qualifies as traumatic stressor. We investigated prevalence and course of posttraumatic stress in patients with early breast cancer (BC) during their first year after diagnosis and determined effects of mastectomy and chemotherapy. METHODS: Patients with stage 0-III BC aged <=65 years were evaluated with the Structured Clinical Interview for DSM-IV modules for acute and posttraumatic stress disorder (ASD and PTSD, respectively) before treatment, after chemotherapy, and 1 year after diagnosis. Matched controls were assessed at matched intervals. Effects of time, mastectomy, and chemotherapy on BC-related PTSD symptom severity were tested with linear mixed model analysis. RESULTS: Stress disorder (ASD or PTSD) related to BC was diagnosed in 6 (3.6%) of 166 patients before treatment and in 3 patients (2.0%) 1 year later. The rate of patients who experienced PTSD symptoms related to BC decreased from 82.5 to 57.3% (p < 0.001), and the mean of BC-related PTSD symptoms diminished from 3.1 to 1.7 (p < 0.001). Only university education significantly predicted the course of BC-related PTSD symptom severity (p = 0.009). In 60 controls, no diagnosis of stress disorder, a rate of 18% women experiencing PTSD symptoms, and a mean of 0.4 PTSD symptoms (p vs. patients <0.001) were found. CONCLUSIONS: Most newly diagnosed patients with BC experience PTSD symptoms, whereas full diagnoses of DSM-IV stress disorder are rare. Symptoms diminish somewhat within 1 year furthered by university education but independently from mastectomy and chemotherapy. Throughout the year after diagnosis, having BC entails markedly increased PTSD symptom burden. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26898733 TI - Nanoscale Polymersomes as Anti-Cancer Drug Carriers Applied for Pharmaceutical Delivery. AB - Polymersomes are self-assembled nano-vesicles composed of amphiphilic block copolymers. These building blocks can be selected from a large number of hydrophilic and hydrophobic polymers in order to achieve required properties of the final system, such as biodegradability, sustainable and multiple stimuli response drug release, long blood circulation, and low toxicity. Moreover, the surface of polymersomes can be functionalized to induce targeting character. Polymersomes are able to encapsulate a broad range of hydrophilic or/and hydrophobic molecules either in the aqueous core or membrane bilayer, respectively. In addition, colloidal stability and low membrane fluidity make polymersomes attractive nano-sized drug carriers. The review describes polymersomes compositions, their applications in pharmaceutical delivery, and preparation methods. PMID- 26898734 TI - Polymeric Based Therapeutic Delivery Systems Prepared Using Electrohydrodynamic Processes. AB - The development of therapeutic dosage (e.g. pharmaceutical) systems is an ongoing process which, in recent times has incorporated several emerging disciplines and themes at timely intervals. While the concepts surrounding dosage forms have developed and evolved, many polymeric excipients remain as the preferred choice of materials over existing counterparts, serving functions as matrix materials, coatings and providing other specific functional properties (e.g. adhesion, controlled release and mechanical properties). There have been, however, developments in the deployment of synthetic polymeric materials (e.g. polycaprolactone, poly lactic co-glycolic acid) when compared to naturally occurring materials (e.g. lactose, gelatin). Advances in pharmaceutical process technologies have also provided novel engineering platforms to develop a host of exciting structure based materials ranging from the nanometer to the macro scales. Some of these structure enabling technologies include spray drying, super critical processing, microfluidics and even wet chemical methods. More recently electrohydrodynamic (EHDA) engineering methods have emerged as robust technologies offering potential to fabricate a plethora of generic structures (e.g. particles, fibres, bubbles and pre-determined patterns) on a broad scale range. This review focuses on key developments using various EHDA technologies for the pharmaceutical and biomaterial remits when selecting synthetic and/or naturally occurring polymers as pharmaceutical (and therapeutic) excipients. In addition, the underlying EHDA process principles are discussed along with key parameters and variables (both materials and engineering). EHDA technologies are operational at ambient conditions and recent developments have also demonstrated their viability for large scale production. These are promising technologies which have potential in established (e.g. films, dressings and microparticles) and emerging scientific themes (e.g. nanomedicines and tissue engineering). PMID- 26898735 TI - Converting Human Proteins into Precision Polymer Therapeutics. AB - Cells as the smallest unit of life rely on precise macromolecules and programmable supramolecular interactions to accomplish the various vital functions. To translate such strategies to precisely control architectures and interactions into the synthetic world represents an exciting endeavor. Polymers with distinct structures, sequences and architectures are still challenging to achieve. However, in particular for biomedical applications, reproducible synthesis, narrow dispersities, tunable functionalities and additionally biocompatibility of the polymeric materials are crucial. Polymers derived from protein precursors provide many advantages of proteins such as precise monomer sequences and contour lengths, biodegradability and multiple functionalities, which can be synergistically combined with the valuable features of synthetic polymers e.g. stability, tunable solubility and molecular weights. The resulting polymeric biohybrid materials offer many applications ranging from drug delivery to biosensing and therapeutic hydrogels. This minireview summarizes the most recent advances in this field. PMID- 26898736 TI - Polymer Self-Assembled Nanostructures as Innovative Drug Nanocarrier Platforms. AB - BACKGROUND: Polymer self-assembled nanostructures are used in pharmaceutical sciences as bioactive molecules' delivery systems for therapeutic and diagnostic purposes. Micelles, polyelectrolyte complexes, polymersomes, polymeric nanoparticles, nanogels and polymer grafted liposomes represent delivery vehicles that are marketed and/or under clinical development, as drug formulations. METHODS: In this mini-review, these, recently appeared in the literature, innovative polymer drug nanocarrier platforms are discussed, starting from their technological development in the laboratory to their potential clinical use, through studies of their biophysics, thermodynamics, physical behavior, morphology, bio-mimicry, therapeutic efficacy and safety. The properties of an ideal drug delivery system are the structural control over size and shape of drug or imaging agent cargo/domain, biocompatibility, nontoxic polymer/ pendant functionality and the precise, nanoscale container and/or scaffolding properties with high drug or imaging agent capacity features. Self-assembled polymer nanostructures exhibit all these properties and could be considered as ideal drug nanocarriers through control of their size, structure and morphology, with the aid of a large variety of parameters, in vitro and in vivo. These modern trends reside at the interface of soft matter self-assembly and pharmaceutical sciences and the technologies for health. CONCLUSION: Great advantages related to basic science and applications are expected by understanding the self-assembly behavior of these polymeric nanotechnological drug delivery systems, created through bio inspiration and biomimicry and have potential utilization into clinical applications. PMID- 26898737 TI - The Production of Solid Dosage Forms from Non-Degradable Polymers. AB - Non-degradable polymers have an important function in medicine. Solid dosage forms for longer term implantation require to be constructed from materials that will not degrade or erode over time and also offer the utmost biocompatibility and biostability. This review details the three most important non-degradable polymers for the production of solid dosage forms - silicone elastomer, ethylene vinyl acetate and thermoplastic polyurethane. The hydrophobic, thermoset silicone elastomer is utilised in the production of a broad range of devices, from urinary catheter tubing for the prevention of biofilm to intravaginal rings used to prevent HIV transmission. Ethylene vinyl acetate, a hydrophobic thermoplastic, is the material of choice of two of the world's leading forms of contraception - Nuvaring(r) and Implanon(r). Thermoplastic polyurethane has such a diverse range of building blocks that this one polymer can be hydrophilic or hydrophobic. Yet, in spite of this versatility, it is only now finding utility in commercialised drug delivery systems. Separately then one polymer has a unique ability that differentiates it from the others and can be applied in a specific drug delivery application; but collectively these polymers provide a rich palette of material and drug delivery options to empower formulation scientists in meeting even the most demanding of unmet clinical needs. Therefore, these polymers have had a long history in controlled release, from the very beginning even, and it is pertinent that this review examines briefly this history while also detailing the state-of the-art academic studies and inventions exploiting these materials. The paper also outlines the different production methods required to manufacture these solid dosage forms as many of the processes are uncommon to the wider pharmaceutical industry. PMID- 26898738 TI - Nanoparticulate Drug Delivery to Colorectal Cancer: Formulation Strategies and Surface Engineering. AB - The evolution of polymer-based nanoparticle as a drug delivery carrier has greatly contributed to the development of advanced nano and micro-medicine in the past few decades. The polymer-based nanoparticles of biodegradable and biocompatible polymers such as poly (lactide-co-glycolide) and chitosan which have been approved by Food & Drug Administration and/or European Medicine Agency can particularly facilitate the maintaining of specific properties for a real transition from laboratory to the clinical oral and parental administration. This review presents an overview of the strategies of preparing polymeric nanoparticles and using them for targeting colorectal cancer. Theranostics and surface engineering aspects of nanoparticle design in colonic cancer delivery are also highlighted. PMID- 26898739 TI - Hypoxia Responsive Drug Delivery Systems in Tumor Therapy. AB - Hypoxia is a common characteristic of solid tumors. It is mainly determined by low levels of oxygen resulting from imperfect vascular networks supplying most tumors. In an attempt to improve the present chemotherapeutic treatment and reduce associated side effects, several prodrug strategies have been introduced to achieve hypoxia-specific delivery of cytotoxic anticancer agents. With the advances in nanotechnology, novel delivery systems activated by the consequent outcomes of hypoxia have been developed. However, developing hypoxia responsive drug delivery systems (which only depend on low oxygen levels) is currently naive. This review discusses four main hypoxia responsive delivery systems: polymeric based drug delivery systems, oxygen delivery systems combined with radiotherapy and chemotherapy, anaerobic bacteria which are used for delivery of genes to express anticancer proteins such as tumor necrosis alpha (TNF-alpha) and hypoxia-inducible transcription factors 1 alpha (HIF1alpha) responsive gene delivery systems. PMID- 26898740 TI - Polymer Particulates in Drug Delivery. AB - Development of effective drug delivery systems is important for medicine and healthcare. Polymer particulates (micro- and nanoparticles) have opened new opportunities in the field of drug delivery by overcoming various limitations of conventional delivery methods. The properties of polymeric particles can be readily tuned by precisely engineering the constituent blocks of polymers for improving drug loading, release rate, pharmacokinetics, targeting, etc. The end groups of various polymers can be readily modified with ligands making them suitable for recognizing by cell-specific receptors, providing cellular specificity, and superior intracellular delivery. This review will mainly cover delivery of many potential drugs and biomolecules by means of polymeric microparticles, nanoparticles and copolymer micelles or assemblies. An overview about formulation methods of polymer particulates has also been addressed. Attempt has been made to cover all the potential polymers that are well known in pharmaceutical history. PMID- 26898741 TI - Polymer Drug Conjugates: Recent Advancements in Various Diseases. AB - During the past decade, the arena of polymer therapeutics has acquired considerable interest and accompanied by advanced designs and chemical properties of polymer-drug conjugates. Various polymers, such as poly (ethylene glycol) (PEG), N-(2-hydroxypropyl) methacrylamide (HPMA), poly(glycolic acid) (PGA) and poly(lactide-co-glycolide) (PLGA) have been used successfully for clinical utilization from decades. These polymers are used in combination of drugs in such a manner that they target the specific tissues and thus the toxicity of drugs to other tissues is reduced. Presently, numerous polymer drug conjugates are under clinical trial for treatment of various diseases including cancer, diabetes, AIDS, rheumatoid arthritis etc. Many protein-polymer conjugates have been approved by FDA for clinical use but till date, no polymer-synthetic drug conjugate is approved by FDA, although many of them are undergoing final phase of clinical trials. This review highlights the recent advancements in the polymer drug conjugates for treatment of various diseases and their preclinical and clinical status. PMID- 26898742 TI - Drug Delivery Systems Based on Polymeric Micelles and Ultrasound: A Review. AB - BACKGROUND: Anti-neoplastic drugs used for cancer treatment often produce damage to healthy cells, leading to severe side effects in patients undergoing chemotherapy. The encapsulation of these agents in nanoparticles reduces the adverse side effects of conventional chemotherapy on healthy tissues. Such nanoparticles, considered as drug delivery vehicles, are diverse and include micelles, liposomes, dendrimers, nanocapsules, nanospheres and others. Polymeric micelles have been widely researched as nanocarriers for hydrophobic drugs. They can be designed to have increased stability and blood circulation time, as well as binding specificity to certain receptors overexpressed on the surface of cancer cells. Once these drug-encapsulating nanoparticles reach the tumor site, an external stimulus, such as ultrasound, can be used to spatially and temporally trigger drug release. METHODS: This review paper focuses on the recent advances of cancer drug delivery systems employing polymeric micelles and ultrasound. An extensive literature review was performed mainly using PubMed. The introduction explains how nanocarriers are related to chemotherapy and the several modalities of use for this application. Afterwards, the review focuses on polymeric micelles used for drug delivery, their advantages and disadvantages. Subsequently, the physics of ultrasound is briefly reviewed, as well as the way it interacts with polymeric micelles to trigger the delivery of the drug transported by these nanocarriers. The following section focuses on targeting, discussing the several ways by which the nanoparticles can be directed to the target cells, and there deliver their cargo. Finally, a selection of relevant in vitro and in vivo studies, as well as clinical trials, is presented and discussed. CONCLUSION: Although there are still several research studies to be performed before the combination of micelles and ultrasound can enter clinical trials, the future of controlled delivery using this drug delivery system is promising as a way to reduce the mortality and morbidity of cancer and the noxious side effects of conventional chemotherapy. PMID- 26898743 TI - Polymer-Based Drug Delivery Systems, Development and Pre-Clinical Status. AB - BACKGROUND: The nanomedicine is considered as the application of nanotechnology in the medical field where nanoparticles are sized in the nanoscale range. Drug delivery technologies are becoming increasingly important as a scientific area of investigation. Controlled-release systems and drug-targeting systems represents an alternative to traditional delivery nanoparticles, and the use of polymers is increasing nowadays. Although polymers could be classified as excipients, they are capable of modifying the biopharmaceutical and biokinetic behaviour of the transported active molecule increasing its efficacy and stability, and reduced cytotoxicity on healthy peripheral tissues. METHODS: The goal of this work is to collect and analyse the most current polymeric nanoparticles development as controlledrelease and drug-targeting systems in cancer, infectious diseases and immunomodulation areas, as alternatives to conventional therapies. RESULTS: This review provides an update on the polymeric nanoparticles development analysing the trend of polymeric-based drug delivery systems, future opportunities and challenges of this fast-growing area. CONCLUSION: With the thorough comprehension of biological effects depending on structure, it is possible to design specific systems for specific diseases, treatments and patients. The ability of polymer- based nanoparticles to modify and improve pharmacokinetics and pharmacodynamics, associated to techniques for enhancement of the therapeutic efficiency with minimal side effects, demonstrate the advantages of these systems. PMID- 26898744 TI - Role of Oxidative Stress and Mitochondrial Dysfunction in Skeletal Muscle in Type 2 Diabetic Patients. AB - Type 2 diabetes can increase the risk of skeletal muscle dysfunction and, consequently, that of cardiovascular diseases, including coronary artery disease and stroke. It is also related to a reduced capacity for exercise, but the underlying mechanism is only partially understood. There are several factors that contribute to the development of skeletal muscle dysfunction, of which oxidative stress and mitochondrial dysfunction are among the most important. This review discusses the role of oxidative stress in the development and progression of skeletal and cardiac dysfunction associated with diabetes. It also provides an overview of the potential actions of antioxidants in general and mitochondria targeted antioxidants in particular in the treatment of muscle dysfunction in type 2 diabetes. PMID- 26898745 TI - Perspectives of Engineered Marine Derived Polymers for Biomedical Nanoparticles. AB - Marine environment exhibits an enormous diversity of organisms which contains an abundant source of polysaccharides. As polymer matrix carriers, marine-based polymers possess several valuable properties including high stability, non toxicity, hydrophilicity, biodegradability, with low production cost. Despite notable biological activities of these natural polymers, there are certain limitations in exploring their functions in applications of nano-sized drug delivery systems. The review aims to demonstrate exceptional characteristics of marine-based polymers including fucoidan, alginate, carrageenan, hyaluronic acid, chondroitin sulfate, and chitosan as well as provide perspectives of current publications on their nanoparticle formulations for biomedical applications. PMID- 26898746 TI - Photochemical etiology of promising ancestors of the RNA nucleobases. AB - RNA is a product of chemical and biological evolution and the identification of its heterocyclic ancestors is essential for understanding the molecular origins of life. Among a diverse array of selection pressures thought to have shaped the composition of the nucleobases on prebiotic Earth, protection against intense ultraviolet radiation must have been essential. In this contribution, a detailed spectroscopic and photophysical investigation of barbituric acid and 2,4,6 triaminopyrimidine, two promising candidates for the prebiotic ancestors of RNA nucleobases, is presented in aqueous solution. It is shown that although these pyrimidine derivatives absorb ultraviolet radiation strongly, both compounds possess efficient electronic relaxation mechanisms for dissipating most of the absorbed ultraviolet energy to their aqueous environment as heat within hundreds of femtoseconds, thus safeguarding their chemical integrity. In fact, these two heterocyclic compounds rival the photostability observed in the canonical nucleobases in aqueous solution, thus supporting the recent proposal that both barbituric acid and 2,4,6-triaminopyrimidine are promising ancestors of the RNA nucleobases. PMID- 26898747 TI - Is nutrient intake associated with physical activity levels in healthy young adults? AB - OBJECTIVE: Both physical activity (PA) and diet are important contributors to health and well-being; however, there is limited information on the association of these behaviours and whether observed associations differ by weight. The present study aimed to evaluate whether nutrient intake is associated with PA and if this association varies by weight in young adults. DESIGN: Cross-sectional study to analyse the association between PA and nutrient intake. SETTING: Participants were stratified as normal weight (18.5 kg/m2 =25.0 kg/m2). PA level (PAL) was calculated (PAL=total daily energy expenditure/RMR) and used to stratify groups (PAL<1.6, 1.6<=PAL<1.9, PAL>=1.9). SUBJECTS: Adults (n 407; age 27.6 (sd 3.8) years, 48 % male), with BMI between 20 and 35 kg/m2, having at least two 24 h diet recalls and at least 5 d (including two weekend days) of valid, objectively measured PA data were included in the analysis. RESULTS: In normal-weight participants, higher PAL was associated with higher intakes of minerals (except Ca, Fe and Zn), B-vitamins and choline (P for trend <0.05). In the overweight/obese group, higher PAL was associated with higher intakes of fibre, K, Na and Cu (P for trend <0.05). These differences, however, were no longer significant after additionally controlling for total energy intake. CONCLUSIONS: More active young adults have higher intakes of essential micronutrients. The benefits of PA may be predominantly due to a higher overall food intake while maintaining energy balance rather than a healthier diet. PMID- 26898749 TI - Maternal cardiac arrest at 26 weeks gestation: birth of a child to term without neurological sequelae. PMID- 26898748 TI - Protocol for the Rural Engagement in Primary Care for Optimizing Weight Reduction (RE-POWER) Trial: Comparing three obesity treatment models in rural primary care. AB - Obesity disproportionately affects rural residents in the United States, and primary care has the potential to fill a major gap in the provision of weight management services for rural communities. The objective of this cluster randomized pragmatic trial is to evaluate the comparative effectiveness of three obesity treatment models in rural primary care: the Intensive Behavior Therapy fee-for-service (FFS) model reimbursed by Medicare, a team-based model that recognizes the patient-centered medical home (PCMH) as a preferred delivery approach, and the centralized disease management (DM) model, in which phone-based counseling is provided outside of the primary care practice. We hypothesize that the PCMH and DM treatments will be more effective than FFS in reducing weight at 24 months. Thirty-six practices from the rural Midwestern U.S. are randomized to deliver one of the three interventions to 40 patients (N=1440) age 20 to 75 with a BMI 30-45 kg/m(2). In the FFS arm, primary care providers and their personnel counsel patients to follow evidence-based weight loss guidelines using the Medicare-designated treatment schedule. In the PCMH arm, patients receive a comprehensive weight management intervention delivered locally by practice personnel using a combination of in-person and phone-based group sessions. In the DM arm, the same intervention is delivered remotely by obesity treatment specialists via group conference calls. The primary outcome is weight loss at 24 months. Additional measures include fasting glucose, lipids, quality of life indicators, and implementation process measures. Findings will illuminate effective obesity treatment intervention(s) in rural primary care. PMID- 26898750 TI - Coupled optical absorption, charge carrier separation, and surface electrochemistry in surface disordered/hydrogenated TiO2 for enhanced PEC water splitting reaction. AB - The central governing factors that influence the efficiency of photoelectrochemical (PEC) water splitting reaction are photon absorption, effective charge-carrier separation, and surface electrochemistry. Attempts to improve one of the three factors may debilitate other factors and we explore such issues in hydrogenated TiO2, wherein a significant increase in optical absorption has not resulted in a significant increase in PEC performance, which we attribute to the enhanced recombination rate due to the formation of amorphization/disorderness in the bulk during the hydrogenation process. To this end, we report a methodology to increase the charge-carrier separation with enhanced optical absorption of hydrogenated TiO2. Current methodology involves hydrogenation of non-metal (N and S) doped TiO2 which comprises (1) lowering of the band gap through shifting of the valence band via less electronegative non metal N, S-doping, (2) lowering of the conduction band level and the band gap via formation of the Ti(3+) state and oxygen vacancies by hydrogenation, and (3) material processing to obtain a disordered surface structure which favors higher electrocatalytic (EC) activity. This design strategy yields enhanced PEC activity (%ABPE = 0.38) for the N-S co-doped TiO2 sample hydrogenated at 800 degrees C for 24 h over possible combinations of N-S co-doped TiO2 samples hydrogenated at 500 degrees C/24 h, 650 degrees C/24 h and 800 degrees C/72 h. This suggests that hydrogenation at lower temperatures does not result in much increase in optical absorption and prolonged hydrogenation results in an increase in optical absorption but a decrease in charge carrier separation by forming disorderness/oxygen vacancies in the bulk. Furthermore, the difference in double layer capacitance (C(dl)) calculated from electrochemical impedance spectroscopy (EIS) measurements of these samples reflects the change in the electrochemical surface area (ECSA) and facilitates assessing the key role of surface electrochemistry in PEC water splitting reaction. Additionally, we observed a blue-shift of the absorption spectrum and a decrease in both electrochemical (EC) and photoelectrochemical (PEC) activities after the removal of surface layers through focused ion beam (FIB) sputtering suggesting the importance of surface defects and photon absorption. PMID- 26898751 TI - Reply to the 'Comment on "An alternative theory to explain the effects of coalescing oil drops on mouthfeel"' by Q. Xia, Soft Matter, 2016, 12, DOI. PMID- 26898752 TI - Introducing context-dependent and spatially-variant viewing biases in saccadic models. AB - Previous research showed the existence of systematic tendencies in viewing behavior during scene exploration. For instance, saccades are known to follow a positively skewed, long-tailed distribution, and to be more frequently initiated in the horizontal or vertical directions. In this study, we hypothesize that these viewing biases are not universal, but are modulated by the semantic visual category of the stimulus. We show that the joint distribution of saccade amplitudes and orientations significantly varies from one visual category to another. These joint distributions are in addition spatially variant within the scene frame. We demonstrate that a saliency model based on this better understanding of viewing behavioral biases and blind to any visual information outperforms well-established saliency models. We also propose a saccadic model that takes into account classical low-level features and spatially-variant and context-dependent viewing biases. This model outperforms state-of-the-art saliency models, and provides scanpaths in close agreement with human behavior. The better description of viewing biases will not only improve current models of visual attention but could also influence many other applications such as the design of human-computer interfaces, patient diagnosis or image/video processing applications. PMID- 26898753 TI - Ultraviolet-visible study on acid-base equilibria of aporphine alkaloids with antiplasmodial and antioxidant activities from Alseodaphne corneri and Dehaasia longipedicellata. AB - The UV-vis spectra of isocorydine 1, norisocorydine 2 and boldine 3 were studied in 2% v/v acetonitrile, at constant ionic strength (0.1 M NaCl, 35 degree Celsius). The pK(a) values of isocorydine 1 and norisocorydine 2 were 11.75 and 12.07, respectively. Boldine 3 gave a pK(a) value of 9.16 and 10.44. All of the alkaloids 1-3 were stable at physiological pH; thereby all of them will not ionize, thus permitting the basic nitrogen to be protonated and accumulated within the acidic food vacuole of Plasmodium via pH trapping. Subsequently, acidic food vacuoles that have been neutralized by alkaloids would result in enhancement of the antiplasmodial activity. The alkaloids showed antiplasmodial activity against Plasmodium falciparum and antioxidant activities; DPPH radical scavenging, metal chelating and ferric reducing power. The antioxidant properties of the alkaloids under investigation revealed that in addition to the antiplasmodial activity, the alkaloids can also prevent oxidative damage. It can be prevented by binding free heme and neutralizing the electrons produced during the Plasmodium falciparum mediated haemoglobin destruction in the host. Slightly basic properties of the aforementioned alkaloids, along with their antioxidant activities, are advantageous in improving the suppression of malaria infection that cause less damage to the host. PMID- 26898754 TI - Reducing dynamic disorder in small-molecule organic semiconductors by suppressing large-amplitude thermal motions. AB - Thermal vibrations and the dynamic disorder they create can detrimentally affect the transport properties of van der Waals bonded molecular semiconductors. The low-energy nature of these vibrations makes it difficult to access them experimentally, which is why we still lack clear molecular design rules to control and reduce dynamic disorder. In this study we discuss the promising organic semiconductors rubrene, 2,7-dioctyl[1]benzothieno[3,2-b][1]benzothio phene and 2,9-di-decyl-dinaphtho-[2,3-b:20,30-f]-thieno-[3,2-b]-thiophene in terms of an exceptionally low degree of dynamic disorder. In particular, we analyse diffuse scattering in transmission electron microscopy, to show that small molecules that have their side chains attached along the long axis of their conjugated core are better encapsulated in their crystal structure, which helps reduce large-amplitude thermal motions. Our work provides a general strategy for the design of new classes of very high mobility organic semiconductors with a low degree of dynamic disorder. PMID- 26898755 TI - Threonine 209 phosphorylation on RUNX3 by Pak1 is a molecular switch for its dualistic functions. AB - P21 Activated Kinase 1 (Pak1), an oncogenic serine/threonine kinase, is known to have a significant role in the regulation of cytoskeleton and cellular morphology. Runx3 was initially known for its role in tumor suppressor function, but recent studies have reported the oncogenic role of Runx3 in various cancers. However, the mechanism that controls the paradoxical functions of Runx3 still remains unclear. In this study, we show that Runx3 is a physiologically interacting substrate of Pak1. We identified the site of phosphorylation in Runx3 as Threonine 209 by mass spectrometry analysis and site-directed mutagenesis, and further confirmed the same with a site-specific antibody. Results from our functional studies showed that Threonine 209 phosphorylation in Runx3 alters its subcellular localization by protein mislocalization from the nucleus to the cytoplasm and subsequently converses its biological functions. This was further supported by in vivo tumor xenograft studies in nude mouse models which clearly demonstrated that PANC-28 cells transfected with the Runx3-T209E clone showed high tumorigenic potential as compared with other clones. Our results from clinical samples also suggest that Threonine 209 phosphorylation by Pak1 could be a potential therapeutic target and of great clinical relevance with implications for Runx3 inactivation in cancer cells where Runx3 is known to be oncogenic. The findings presented in this study provide evidence of Runx3-Threonine 209 phosphorylation as a molecular switch in dictating the tissue-specific dualistic functions of Runx3 for the first time. PMID- 26898756 TI - A crucial role of SUMOylation in modulating Sirt6 deacetylation of H3 at lysine 56 and its tumor suppressive activity. AB - Sirt6 is a histone deacetylase with NAD(+)-dependent activity. Sirt6 has been shown as a tumor suppressor partially via inhibiting the expression of c-Myc target genes and ribosome biogenesis. However, how to regulate Sirt6 activity is largely unknown. In this study, we identify that Sirt6 can be modified by small ubiquitin-like modifier. Sirt6 SUMOylation deficiency specifically decreases its deacetylation of H3K56 but not H3K9 in vivo. Mechanistically, we find that SUMOylation deficiency decreases Sirt6 binding with c-Myc, decreasing Sirt6 occupancy on the locus of c-Myc target genes. Therefore, Sirt6 SUMOylation deficiency reduces its deacetylation of H3k56 and its repression of c-Myc target genes. Moreover, Sirt6 SUMOylation deficiency reduces its suppression of cell proliferation and tumorigenesis. Thus, these results reveal that SUMOylation has an important role in regulation of Sirt6 deacetylation on H3K56, as well as its tumor suppressive activity. PMID- 26898757 TI - The microRNA-23b/-27b cluster suppresses prostate cancer metastasis via Huntingtin-interacting protein 1-related. AB - Deregulation of microRNAs (miRs) contributes to progression and metastasis of prostate and other cancers. miR-23b and -27b, encoded in the same miR cluster (miR-23b/-27b), are downregulated in human metastatic prostate cancer compared with primary tumors and benign tissue. Expression of miR-23b/-27b decreases prostate cancer cell migration, invasion and results in anoikis resistance. Conversely, antagomiR-mediated miR-23b and -27b silencing produces the opposite result in a more indolent prostate cancer cell line. However, neither miR-23b/ 27b expression or inhibition impacts prostate cancer cell proliferation suggesting that miR-23b/-27b selectively suppresses metastasis. To examine the effects of miR-23b/-27b on prostate cancer metastasis in vivo, orthotopic prostate xenografts were established using aggressive prostate cancer cells transduced with miR-23b/-27b or non-targeting control miRNA. Although primary tumor formation was similar between miR-23b/-27b-transduced cells and controls, miR-23b/-27b expression in prostate cancer cells decreased seminal vesicle invasion and distant metastases. Gene-expression profiling identified the endocytic adaptor, Huntingtin-interacting protein 1-related (HIP1R) as being downregulated by miR-23b/-27b. Increased HIP1R expression in prostate cancer cells inversely phenocopied the effects of miR-23b/-27b overexpression on migration, invasion and anchorage-independent growth. HIP1R rescued miR-23b/-27b mediated repression of migration in prostate cancer cells. HIP1R mRNA levels were decreased in seminal vesicle tissue from mice bearing miR-23b/-27b-transduced prostate cancer cell xenografts compared with scrambled controls, suggesting HIP1R is a key functional target of miR-23b/-27b. In addition, depletion of HIP1R led to a more rounded, less mesenchymal-like cell morphology, consistent with decreased metastatic properties. Together, these data demonstrate that the miR 23b/-27b cluster functions as a metastasis-suppressor by decreasing HIP1R levels in pre-clinical models of prostate cancer. PMID- 26898758 TI - Epigenetic modulation of a miR-296-5p:HMGA1 axis regulates Sox2 expression and glioblastoma stem cells. AB - Solid malignancies contain subsets of multipotent cells that grow as spheres and efficiently propagate tumors in xenograft models, reflecting a stem-like, self renewing and tumor-propagating phenotype. These cancer 'stem cells (SCs)' have been shown to maintain tumor growth, contribute to resistance and drive tumor recurrence. Cancer cell stemness is dynamically influenced by epigenetic mechanisms and differentially regulated coding and noncoding RNAs. How these mechanisms specifically contribute to the generation and/or maintenance of cancer SCs remains unclear. This study identifies a novel epigenetically regulated circuit that integrates microRNA, chromatin remodeling and the reprogramming transcription factor Sox2 to regulate glioblastoma (GBM)-propagating SCs. We show that miR-296-5p expression is repressed in a DNA methylation-dependent manner under conditions that promote GBM cell stemness and that miR-296-5p inhibits GBM cell stemness and their capacity to self-renew as spheres and propagate glioma xenografts in vivo. We show that the chromatin remodeling protein HMGA1 functions as a downstream effector of these biological responses to miR-296-5p and regulates Sox2 expression, a master driver of cell stemness, by modifying chromatin architecture at the Sox2 promoter. These results show for the first time that miR-296-5p inhibits transcriptional mechanisms that support GBM SCs and identify a miR-296-5p:HMGA1:Sox2 axis as a novel regulator of GBM SCs and candidate pathway for targeting therapies directed at depleting tumors of their tumor-propagating stem cell subsets. PMID- 26898761 TI - A rare location for fibrous dysplasia. The middle turbinate. PMID- 26898762 TI - Endoscopic septoplasty: Learning curve. AB - AIMS: The aim of the current study was to report the learning curve for endoscopic septoplasty for a senior surgeon already trained in endonasal sinus surgery. MATERIAL AND METHODS: From November 2011 to September 2012, 100 patients were prospectively included and grouped in 5 consecutive groups of 20 by date of surgery. The primary endpoint was operative time. Intra- and postoperative complications and functional assessment were also analyzed. RESULTS: Operative time decreased with the surgeon's experience and became stable after 60 procedures. Operative time saving was about 10min per 20 procedures. Mean operative time was stable between groups 4 (21.1+/-9.6min) and 5 (19.2+/-8.2min). There was a 2% rate of conversion to conventional surgery for technical problems. The number of procedures free of accidental mucosal lesion increased and became stable after 40 procedures. There was a 4% rate of residual postoperative perforation. Nasal Obstruction and Septoplasty Effectiveness (NOSE) score improved postoperatively in each group (P<0.05). CONCLUSION: After 60 endoscopic septoplasty procedures, a senior surgeon masters the surgical technique with satisfactory operative times, and a decreasing rate of intra- and postoperative complications. PMID- 26898759 TI - TRIMming p53's anticancer activity. AB - Several TRIM proteins control abundance and activity of p53. Along this route, TRIM proteins have a serious impact on carcinogenesis and prognosis for cancer patients. In the past years, a significant increase has been made in our understanding of how the TRIM protein family controls p53 activity. PMID- 26898760 TI - PARP1 enhances lung adenocarcinoma metastasis by novel mechanisms independent of DNA repair. AB - The role of poly (ADP-ribose) polymerase 1 (PARP1) in cancer has been extensively studied in the context of DNA repair, leading to clinical trials of PARP1 inhibitors in cancers defective in homologous recombination. However, the DNA repair-independent roles of PARP1 in carcinogenesis and metastasis, particularly in lung cancer metastasis, remain largely uncharacterized. Here, we report that PARP1 promotes lung adenocarcinoma relapse to the brain and bones by regulating several steps of the metastatic process in a DNA repair-independent manner. We find that PARP1 expression is associated with overall and distant metastasis-free survival in lung adenocarcinoma patients. Consistent with this, genetic knockdown and pharmacological inhibition of PARP1 significantly attenuated the metastatic potential of lung adenocarcinoma cells. Further investigation revealed that PARP1 potentiates lung adenocarcinoma metastasis by promoting invasion, anoikis resistance, extravasation and self-renewal of lung adenocarcinoma cells and also by modifying the brain microenvironment. Finally, we identified S100A4 and CLDN7 as novel transcriptional targets and clinically relevant effectors of PARP1. Collectively, our study not only revealed previously unknown functions of PARP1 in lung adenocarcinoma metastasis but also delineated the molecular mechanisms underlying the pro-metastatic function of PARP1. Furthermore, these findings provide a foundation for the potential use of PARP1 inhibitors as a new treatment option for lung adenocarcinoma patients with elevated PARP1 expression. PMID- 26898763 TI - Medial longitudinal arch biomechanics evaluation during gait in subjects with flexible flatfoot. AB - PURPOSE: Medial longitudinal arch (MLA) strengthening has been considered an important part of successful flatfoot treatment. But, to date, the biomechanical loading behavior of the medial arch in flatfoot has not been evaluated. This study aimed to evaluate the MLA moment, MLA deformation angle, foot kinematics and ground reaction forces (GRF) in both normal foot and flatfoot groups. METHODS: Each participant's foot was classified according to arch type using foot prints and radiographs. Twenty-eight non-obese adults (13 flatfeet and 15 normal feet) were involved. The biomechanics data were collected in a 3D motion analysis laboratory. The MLA biomechanics were calculated. Hindfoot and forefoot kinematics were also analyzed. RESULTS: The flatfoot group had a significantly greater peak eversion MLA moment (p = 0.005) and a smaller peak MLA deformation angle (p < 0.05) during specific subphases. The peak of hindfoot plantarflexion (p < 0.05) and internal rotation (p < 0.05) and the peak of forefoot abduction ( p < 0.05) in the specific subphases were greater in the flatfoot group. The flatfoot group also had significantly smaller peak vertical GRF ( p < 0.05) during late stance and larger peak medial GRF (p < 0.05) during mid stance. CONCLUSIONS: This study found a significantly greater eversion deforming force acting at the MLA structure, greater hindfoot and forefoot motion, less MLA flexibility and abnormal GRF in a flatfoot group during walking, which reflected the deficit of foot function in a flatfoot group. PMID- 26898764 TI - Identification of a novel HLA-C*16 variant, HLA-C*16:90, in a Chinese individual. AB - The novel HLA-C*16:90 allele differs from HLA-C*16:02:01 by one nucleotide transition, G>A 736. PMID- 26898765 TI - Unicompartmental knee replacement: Does the macroscopic status of the anterior cruciate ligament affect outcome? AB - PURPOSE: ACL damage is associated with progression of arthritis and whilst in the population undergoing joint replacement in the majority of cases the ACL is intact there is a wide spectrum of ACL disease. This study investigated whether the macroscopic status of the ACL affected functional outcome or survival following UKR. METHODS: The macroscopic status of the ACL was recorded in 820 cemented Oxford UKRs implanted by two surgeons for the recommended indications. The ACL was considered functionally normal in the setting of anteromedial tibial wear and macroscopically the ACL visually appeared normal or had synovial damage or longitudinal splits. The patients were followed up independently with a mean follow-up of 10.3years (range 5.3 to 16.6). RESULTS: More marked ACL macroscopic damage was significantly associated with increasing age, male gender and a more extensive anteromedial tibial defect. Patients with more ACL damage had a significantly lower pre-operative AKSS Objective Score, however no difference in AKSS-Functional or OKS was detected between groups. At 10years no difference in functional outcome or activity level was found between groups. Compared to those with a macroscopically normal ACL at 10years a significantly greater improvement from baseline OKS score was seen in patients with macroscopic ACL abnormalities. At 15years no difference in implant survival, or failure mechanism, was detected between groups. CONCLUSION: The macroscopic status of the ACL does not affect long term functional outcomes or implant survival and in the setting of an intact ACL macroscopic status is not a contraindication to mobile bearing UKR. LEVEL OF EVIDENCE: Level IV. PMID- 26898766 TI - Correlation between histological outcome and surgical cartilage repair technique in the knee: A meta-analysis. AB - BACKGROUND: Compare histological outcomes after microfracture (MF), autologous chondrocyte implantation (ACI), and osteochondral autograft transfer (OATS). METHODS: Literature review using PubMed MEDLINE, SCOPUS, Cumulative Index for Nursing and Allied Health Literature (CINAHL), and Cochrane Collaboration Library. Inclusion criteria limited to English language studies International Cartilage Repair Society (ICRS) grading criteria for cartilage analysis after ACI (autologous chondrocyte implantation), MF (microfracture), or OATS (osteochondral autografting) repair techniques. RESULTS: Thirty-three studies investigating 1511 patients were identified. Thirty evaluated ACI or one of its subtypes, six evaluated MF, and seven evaluated OATS. There was no evidence of publication bias (Begg's p=0.48). No statistically significant correlation was found between percent change in clinical outcome and percent biopsies showing ICRS Excellent scores (R(2)=0.05, p=0.38). Percent change in clinical outcome and percent of biopsies showing only hyaline cartilage were significantly associated (R(2)=0.24, p=0.024). Mean lesion size and histological outcome were not correlated based either on percent ICRS Excellent (R(2)=0.03, p=0.50) or percent hyaline cartilage only (R(2)=0.01, p=0.67). Most common lesion location and histological outcome were not correlated based either on percent ICRS Excellent (R(2)=0.03, p=0.50) or percent hyaline cartilage only (R(2)=0.01, p=0.67). CONCLUSIONS: Microfracture has poorer histologic outcomes than other cartilage repair techniques. OATS repairs primarily are comprised of hyaline cartilage, followed closely by cell based techniques, but no significant difference was found cartilage quality using ICRS grading criteria among OATS, ACI-C, MACI, and ACI-P. LEVEL OF EVIDENCE: IV, meta-analysis. PMID- 26898767 TI - The infrapatellar fat pad is affected by injury induced inflammation in the rabbit knee: use of dexamethasone to mitigate damage. AB - OBJECTIVE AND DESIGN: The health of the infrapatellar fat pad (IFP) has been linked to pain, joint inflammation, and the onset of post-traumatic osteoarthritis. Thus, early inflammation effects on the IFP could have long term sequelae on joint integrity. This study was designed to characterize the natural history of the IFP in a model of surgically induced knee injury and inflammation, and to test the efficacy of one intra-articular (IA) administration of dexamethasone (DEX) immediately following surgery. METHODS: An IA bone drill hole injury to the rabbit knee was conducted and immediately treated with DEX (n = 12). Early and late post-surgical time-points were investigated (48 h and 9 weeks) and the outcome measures were analysis of IFP histology, mRNA levels for relevant molecules, and protein levels for a subset of cytokines. Data were analyzed against a surgical control (injury without treatment; n = 12), a surgical sham (capsular incision only; n = 12), and normal control (n = 6). TREATMENT: Single IA injection of DEX (0.5 mg/kg), administered at the completion of surgery. RESULTS: IFPs from injured joints exhibited significantly increased cellularity and early fibrosis at 48 h post surgery. While the histological inflammation from a capsular incision alone resolved, knee injured animals progressed to a significantly more fibrotic IFP by 9 weeks. DEX significantly lowered histological scores at 48 h, but not at the 9 weeks. DEX did not influence mRNA levels for IL-1beta, 6, and 8, however, protein analysis indicated that IL-8 levels were lower in DEX treated joints. DEX resulted in significantly elevated expression of mRNA for MCP-1, leptin, and VEGF. CONCLUSION: One IA administration of a glucocorticoid appears to mitigate the initial inflammation within the joint, but is not sufficient to protect the joint to 9 weeks post surgery. PMID- 26898769 TI - Glucosylation of Catechol with the GTFA Glucansucrase Enzyme from Lactobacillus reuteri and Sucrose as Donor Substrate. AB - Lactic acid bacteria use glucansucrase enzymes for synthesis of gluco oligosaccharides and polysaccharides (alpha-glucans) from sucrose. Depending on the glucansucrase enzyme, specific alpha-glucosidic linkages are introduced. GTFA DeltaN (N-terminally truncated glucosyltransferase A) is a glucansucrase enzyme of Lactobacillus reuteri 121 that synthesizes the reuteran polysaccharide with (alpha1 -> 4) and (alpha1 -> 6) glycosidic linkages. Glucansucrases also catalyze glucosylation of various alternative acceptor substrates. At present it is unclear whether the linkage specificity of these enzymes is the same in oligo/polysaccharide synthesis and in glucosylation of alternative acceptor substrates. Our results show that GTFA-DeltaN glucosylates catechol into products with up to at least 5 glucosyl units attached. These catechol glucosides were isolated and structurally characterized using 1D/2D (1)H NMR spectroscopy. They contained 1 to 5 glucose units with different (alpha1 -> 4) and (alpha1 -> 6) glycosidic linkage combinations. Interestingly, a branched catechol glucoside was also formed along with a catechol glucoside with 2 successive (alpha1 -> 6) glycosidic linkages, products that are absent when only sucrose is used as both glycosyl donor and acceptor substrate. PMID- 26898768 TI - Straightforward and sensitive RT-qPCR based gene expression analysis of FFPE samples. AB - Fragmented RNA from formalin-fixed paraffin-embedded (FFPE) tissue is a known obstacle to gene expression analysis. In this study, the impact of RNA integrity, gene-specific reverse transcription and targeted cDNA preamplification was quantified in terms of reverse transcription polymerase chain reaction (RT-qPCR) sensitivity by measuring 48 protein coding genes on eight duplicate cultured cancer cell pellet FFPE samples and twenty cancer tissue FFPE samples. More intact RNA modestly increased gene detection sensitivity by 1.6 fold (earlier detection by 0.7 PCR cycles, 95% CI = 0.593-0.850). Application of gene-specific priming instead of whole transcriptome priming during reverse transcription further improved RT-qPCR sensitivity by a considerable 4.0 fold increase (earlier detection by 2.0 PCR cycles, 95% CI = 1.73-2.32). Targeted cDNA preamplification resulted in the strongest increase of RT-qPCR sensitivity and enabled earlier detection by an average of 172.4 fold (7.43 PCR cycles, 95% CI = 6.83-7.05). We conclude that gene-specific reverse transcription and targeted cDNA preamplification are adequate methods for accurate and sensitive RT-qPCR based gene expression analysis of FFPE material. The presented methods do not involve expensive or complex procedures and can be easily implemented in any routine RT qPCR practice. PMID- 26898770 TI - An association between belief in life after death and serum oxytocin in older people in rural Japan. AB - OBJECTIVE: Previous research suggests that spirituality/religiosity has benefits for both mental and physical health, measured using biological indices such as cortisol and IL-6. However, there have been few studies concerning the association of religious beliefs with oxytocin, a neuropeptide hormone secreted by the pituitary. Levels of peripheral oxytocin are thought to reflect the strength of bonding and stress regulation in social relationships. As such, the oxytocin system may underpin the biological mechanisms by which belief in life after death is associated with good mental and physical health. Here, we examine associations between oxytocin and belief in life after death. METHODS: We recruited 317 community-dwelling people, aged 65 or older, without cognitive or mental deficits, and living in rural Japan. We recorded demographics, belief in life after death, and logical memory using the Wechsler Memory Scale. Levels of serum oxytocin were obtained using an enzyme immunoassay method. RESULTS: Serum oxytocin levels were higher among women than men and were negatively associated with strength of belief in life after death. CONCLUSIONS: Our findings could be interpreted differently depending on whether the anxiogenic or anxiolytic function of the oxytocin system is considered. Greater endorsement of afterlife beliefs may reduce secure attachment. Alternatively, based on the literature suggesting that basal levels of oxytocin are lower in those with reduced relational distress or anxiety, afterlife beliefs may play a role in these reductions. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26898771 TI - A sensorimotor area in the songbird brain is required for production of vocalizations in the song learning period of development. AB - Sensory feedback is essential for acquiring and maintaining complex motor behaviors, including birdsong. In zebra finches, auditory feedback reaches the song control circuits primarily through the nucleus interfacialis nidopalii (Nif), which provides excitatory input to HVC (proper name)-a premotor region essential for the production of learned vocalizations. Despite being one of the major inputs to the song control pathway, the role of Nif in generating vocalizations is not well understood. To address this, we transiently inactivated Nif in late juvenile zebra finches. Upon Nif inactivation (in both hemispheres or on one side only), birds went from singing stereotyped zebra finch song to uttering highly variable and unstructured vocalizations resembling sub-song, an early juvenile song form driven by a basal ganglia circuit. Simultaneously inactivating Nif and LMAN (lateral magnocellular nucleus of the anterior nidopallium), the output nucleus of a basal ganglia circuit, inhibited song production altogether. These results suggest that Nif is required for generating the premotor drive for song. Permanent Nif lesions, in contrast, have only transient effects on vocal production, with song recovering within a day. The sensorimotor nucleus Nif thus produces a premotor drive to the motor pathway that is acutely required for generating learned vocalizations, but once permanently removed, the song system can compensate for its absence. (c) 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1213-1225, 2016. PMID- 26898772 TI - High rate lithium-sulfur battery enabled by sandwiched single ion conducting polymer electrolyte. AB - Lithium-sulfur batteries are highly promising for electric energy storage with high energy density, abundant resources and low cost. However, the battery technologies have often suffered from a short cycle life and poor rate stability arising from the well-known "polysulfide shuttle" effect. Here, we report a novel cell design by sandwiching a sp(3) boron based single ion conducting polymer electrolyte film between two carbon films to fabricate a composite separator for lithium-sulfur batteries. The dense negative charges uniformly distributed in the electrolyte membrane inherently prohibit transport of polysulfide anions formed in the cathode inside the polymer matrix and effectively blocks polysulfide shuttling. A battery assembled with the composite separator exhibits a remarkably long cycle life at high charge/discharge rates. PMID- 26898773 TI - Characteristics of Cerebral Hemodynamics in Patients with Ischemic Leukoaraiosis and New Ultrasound Indices of Ischemic Leukoaraiosis. AB - OBJECTIVE: The diagnosis of ischemic leukoaraiosis (ILA) is based on head magnetic resonance imaging (MRI) and exclusion of other causes of white matter hyperintensities (WMHs). Recent studies have shown increased arterial stiffness and diminished carotid flow in ILA patients. So far, there are very little data on intracerebral hemodynamic parameters in ILA. Due to the specific structure of the intracranial arteries, our aim was to investigate intracerebral hemodynamic parameters in ILA patients and, possibly, to find a reliable ultrasound index of combined intra- and extracranial cerebral arteries. METHODS: We compared different hemodynamic parameters in the middle cerebral artery (MCA) and local carotid stiffness parameters in 53 ILA patients to 40 gender and risk factor matched controls with normal head MRI. The ILA diagnosis was based on head MRI and exclusion of other causes of WMH. In addition, we introduced new ischemic leukoariosis indices (ILAi) that are ratios of carotid stiffness parameters and MCA mean blood flow velocity. The diagnostic significance of ILAi for the prediction of ILA was analyzed. RESULTS: We found significantly lower diastolic, systolic, and mean MCA blood flow velocities and increased carotid stiffness in the ILA group (P <= .05). All ILAi significantly differed between the groups (P < .05), were significantly associated with ILA (P < .01), and were sensitive and specific for predicting ILA (P < .05). CONCLUSION: MCA blood flow velocities in ILA patients are lower compared to risk factor-matched controls. A combination of lower velocities and increased carotid stiffness represented as ILAi could have a potential diagnostic value for ILA. PMID- 26898774 TI - Rovibrationally Excited Molecules on the Verge of a Triple Breakdown: Molecular and Roaming Mechanisms in the Photodecomposition of Methyl Formate. AB - For the photodissociation of the simplest of esters, methyl formate HCOOCH3, the energy threshold for triple fragmentation into H, CH3O, and CO was measured by previous ion-imaging experiments at a sequence of wavelengths. The translational energy features of product CO in the ground vibrational level (upsilon = 0) and for selected rotational states were characterized. In this integrated experimental and theoretical approach (i) the focus is at a laser energy barely below that threshold; (ii) Fourier-transform infrared emission spectroscopy measurements probe the rovibrational energy deposition in CO(upsilon) for upsilon > 0 and the emergence of the roaming phenomenon; (iii) accompanying quantum chemical calculations describe the selective rupture of bonds; and (iv) molecular dynamics simulations of dissociation are performed, introducing an approach explicitly involving outcomes from paths originated nonadiabatically through conical intersections. Quantitative information on energy disposal is provided: we found extensive vibrational excitation of CO, while rotational bands are colder and bimodal, due to contributions from direct and roaming modes. PMID- 26898775 TI - Cannabinoid Control of Learning and Memory through HCN Channels. AB - The mechanisms underlying the effects of cannabinoids on cognitive processes are not understood. Here we show that cannabinoid type-1 receptors (CB1Rs) control hippocampal synaptic plasticity and spatial memory through the hyperpolarization activated cyclic nucleotide-gated (HCN) channels that underlie the h-current (Ih), a key regulator of dendritic excitability. The CB1R-HCN pathway, involving c-Jun-N-terminal kinases (JNKs), nitric oxide synthase, and intracellular cGMP, exerts a tonic enhancement of Ih selectively in pyramidal cells located in the superficial portion of the CA1 pyramidal cell layer, whereas it is absent from deep-layer cells. Activation of the CB1R-HCN pathway impairs dendritic integration of excitatory inputs, long-term potentiation (LTP), and spatial memory formation. Strikingly, pharmacological inhibition of Ih or genetic deletion of HCN1 abolishes CB1R-induced deficits in LTP and memory. These results demonstrate that the CB1R-Ih pathway in the hippocampus is obligatory for the action of cannabinoids on LTP and spatial memory formation. PMID- 26898776 TI - Developmental Inhibition of Gsk3 Rescues Behavioral and Neurophysiological Deficits in a Mouse Model of Schizophrenia Predisposition. AB - While the genetic basis of schizophrenia is increasingly well characterized, novel treatments will require establishing mechanistic relationships between specific risk genes and core phenotypes. Rare, highly penetrant risk genes such as the 22q11.2 microdeletion are promising in this regard. Df(16)A(+/-) mice, which carry a homologous microdeletion, have deficits in hippocampal-prefrontal connectivity that correlate with deficits in spatial working memory. These mice also have deficits in axonal development that are accompanied by dysregulated Gsk3beta signaling and can be rescued by Gsk3 antagonists. Here we show that developmental inhibition of Gsk3 rescues deficits in hippocampal-prefrontal connectivity, task-related neural activity, and spatial working memory behavior in Df(16)A(+/-) mice. Taken together, these results provide mechanistic insight into how the microdeletion results in cognitive deficits, and they suggest possible targets for novel therapies. PMID- 26898777 TI - Grid Cell Responses in 1D Environments Assessed as Slices through a 2D Lattice. AB - Grid cells, defined by their striking periodic spatial responses in open 2D arenas, appear to respond differently on 1D tracks: the multiple response fields are not periodically arranged, peak amplitudes vary across fields, and the mean spacing between fields is larger than in 2D environments. We ask whether such 1D responses are consistent with the system's 2D dynamics. Combining analytical and numerical methods, we show that the 1D responses of grid cells with stable 1D fields are consistent with a linear slice through a 2D triangular lattice. Further, the 1D responses of comodular cells are well described by parallel slices, and the offsets in the starting points of the 1D slices can predict the measured 2D relative spatial phase between the cells. From these results, we conclude that the 2D dynamics of these cells is preserved in 1D, suggesting a common computation during both types of navigation behavior. PMID- 26898780 TI - Structured Dendritic Inhibition Supports Branch-Selective Integration in CA1 Pyramidal Cells. AB - Neuronal circuit function is governed by precise patterns of connectivity between specialized groups of neurons. The diversity of GABAergic interneurons is a hallmark of cortical circuits, yet little is known about their targeting to individual postsynaptic dendrites. We examined synaptic connectivity between molecularly defined inhibitory interneurons and CA1 pyramidal cell dendrites using correlative light-electron microscopy and large-volume array tomography. We show that interneurons can be highly selective in their connectivity to specific dendritic branch types and, furthermore, exhibit precisely targeted connectivity to the origin or end of individual branches. Computational simulations indicate that the observed subcellular targeting enables control over the nonlinear integration of synaptic input or the initiation and backpropagation of action potentials in a branch-selective manner. Our results demonstrate that connectivity between interneurons and pyramidal cell dendrites is more precise and spatially segregated than previously appreciated, which may be a critical determinant of how inhibition shapes dendritic computation. PMID- 26898778 TI - Cross-Modality Sharpening of Visual Cortical Processing through Layer-1-Mediated Inhibition and Disinhibition. AB - Cross-modality interaction in sensory perception is advantageous for animals' survival. How cortical sensory processing is cross-modally modulated and what are the underlying neural circuits remain poorly understood. In mouse primary visual cortex (V1), we discovered that orientation selectivity of layer (L)2/3, but not L4, excitatory neurons was sharpened in the presence of sound or optogenetic activation of projections from primary auditory cortex (A1) to V1. The effect was manifested by decreased average visual responses yet increased responses at the preferred orientation. It was more pronounced at lower visual contrast and was diminished by suppressing L1 activity. L1 neurons were strongly innervated by A1 V1 axons and excited by sound, while visual responses of L2/L3 vasoactive intestinal peptide (VIP) neurons were suppressed by sound, both preferentially at the cell's preferred orientation. These results suggest that the cross-modality modulation is achieved primarily through L1 neuron- and L2/L3 VIP-cell-mediated inhibitory and disinhibitory circuits. PMID- 26898781 TI - Food patterns and the prevention of depression. AB - An emerging field of research in nutritional epidemiology is the assessment of several links between nutritional quality and mental health. Specifically, some studies have pointed out that several food patterns could be associated with a reduced risk of depression among adults. This association seems to be consistent across countries, cultures and populations according to several systematic reviews and meta-analyses of observational studies. Some previously described food patterns, specifically the Mediterranean Food Pattern, the Alternative Healthy Eating Index, the Prudent diet or the Provegetarian Food Pattern may be effective to reduce the future risk of depression. Among them, only the Mediterranean Food Pattern has been tested for primary prevention in a large randomised trial, but the inverse association found was not statistically significant. The scientific report of the 2015 Dietary Guidelines for Americans Advisory Committee concluded that current evidence is still limited. Notwithstanding, this field is promising and, according to large and well conducted observational studies, food patterns potentially associated with reduced risk of depression are those emphasising seafood, vegetables, fruits and nuts. There is a need to assess whether differences in the intake of some micro or macronutrients between these dietary patterns can make a difference in their association with a lower risk of depression. Moreover, the shape of the dose response curve and the potential existence of a nonlinear threshold effect have not yet been established. PMID- 26898782 TI - Development and Validation of HealthImpact: An Incident Diabetes Prediction Model Based on Administrative Data. AB - OBJECTIVE: To develop and validate a model of incident type 2 diabetes based solely on administrative data. DATA SOURCES/STUDY SETTING: Optum Labs Data Warehouse (OLDW), a national commercial administrative dataset. STUDY DESIGN: HealthImpact model was developed and internally validated using nested case control study design; n = 473,049 in training cohort and n = 303,025 in internal validation cohort. HealthImpact was externally validated in 2,000,000 adults followed prospectively for 3 years. Only adults >=18 years were included. DATA COLLECTION/EXTRACTION METHODS: Patients with incident diabetes were identified using HEDIS rules. Control subjects were sampled from patients without diabetes. Medical and pharmacy claims data collected over 3 years prior to index date were used to build the model variables. PRINCIPAL FINDINGS: HealthImpact, scored 0 100, has 48 variables with c-statistic 0.80815. We identified HealthImpact threshold of 90 as identifying patients at high risk of incident diabetes. HealthImpact had excellent discrimination in external validation cohort (c statistic 0.8171). The sensitivity, specificity, positive predictive value, and negative predictive value of HealthImpact >90 for new diagnosis of diabetes within 3 years were 32.35, 94.92, 22.25, and 96.90 percent, respectively. CONCLUSIONS: HealthImpact is an efficient and effective method of risk stratification for incident diabetes that is not predicated on patient-provided information or laboratory tests. PMID- 26898783 TI - A model system for the study of gene expression in the undergraduate laboratory. AB - The flow of genetic information from DNA to RNA to protein, otherwise known as the "central dogma" of biology, is one of the most basic and overarching concepts in the biological sciences. Nevertheless, numerous studies have reported student misconceptions at the undergraduate level of this fundamental process of gene expression. This study reports on the efficacy of a model system for teaching gene expression in the undergraduate laboratory. A student-centered investigation of Tgfb1 gene expression in two murine melanoma cell lines was used to emphasize not only the process of gene expression but also various research methods for studying this phenomenon. Traditional RT-PCR, quantitative real-time RT-PCR, and flow cytometry-based in situ hybridization assays were employed to study expression of this immunosuppressive cytokine gene in the highly tumorigenic B16 F1 melanoma cell line and the poorly tumorigenic D5.1G4 melanoma cell line, both at the population and single-cell levels. A pre- and post-laboratory assessment instrument demonstrated the utility of this model system in enhancing student learning both of content related to gene expression and of research methods and data analysis skills. The pedagogical approach described in this study is therefore an effective way to improve the teaching and learning of gene expression at the undergraduate level. (c) 2016 by The International Union of Biochemistry and Molecular Biology, 44(4):397-404, 2016. PMID- 26898779 TI - A Systems-Level Analysis of the Peripheral Nerve Intrinsic Axonal Growth Program. AB - The regenerative capacity of the injured CNS in adult mammals is severely limited, yet axons in the peripheral nervous system (PNS) regrow, albeit to a limited extent, after injury. We reasoned that coordinate regulation of gene expression in injured neurons involving multiple pathways was central to PNS regenerative capacity. To provide a framework for revealing pathways involved in PNS axon regrowth after injury, we applied a comprehensive systems biology approach, starting with gene expression profiling of dorsal root ganglia (DRGs) combined with multi-level bioinformatic analyses and experimental validation of network predictions. We used this rubric to identify a drug that accelerates DRG neurite outgrowth in vitro and optic nerve outgrowth in vivo by inducing elements of the identified network. The work provides a functional genomics foundation for understanding neural repair and proof of the power of such approaches in tackling complex problems in nervous system biology. PMID- 26898785 TI - Laparoscopic management of pancreatic cancer. Our experience. AB - AIM: Minimally invasive techniques have a definite role in the surgical treatment of several gastrointestinal tract cancers but there is still no widespread use of the laparoscopic approach for cancers of the head of the pancreas. The aim of this retrospective study is to review our experience from 2003 to 2013 in the management of pancreatic cancer with particular emphasis on the clinical application of minimally invasive techniques. METHODS: One hundred fifty-eight pancreatic cancer patients (median age 69,7+/-12,6 years) with obstructive jaundice were enrolled in our study. One hundred eighteen (74,7%) had an endoscopic biliary stent, 68 patients (43,03%) were eligible for surgery. Only 22 of the patients eligible for surgical intervention underwent pancreaticoduodenectomy (PD): 14 had open PD and 8 had laparoscopic PD (LPD). Thirteen of the PD patients had a pylorus-preserving procedure (8 open and 5 laparoscopic procedures) whereas in 9 the pylorus was not preserved (6 open and 3 laparoscopic procedures). The other 46 patients had un-resectable tumors and 34 of them underwent palliative surgery consisting of gastrojejunal and hepatojejunal anastomosis (18 open and 6 laparoscopic procedures), and gastrojejunal anastomosis in 10 patients (4 open and 6 laparoscopic procedures). Ten patients had only explorative laparoscopy and 2 only explorative laparotomy. RESULTS: The resectability rate was 13,9%. The median age in patients treated with an endoscopic biliary stent was significantly higher than in those who underwent surgery (73,2+/-13,3 years vs 64,4+/-9,6 years; p < 0,05). Operative time in LPD patients was significantly longer than in PD patients (521+/-68 minutes vs 381+/-88 minutes; p<0.05). The hospital stay of patients who underwent PD was significantly longer than that of those who underwent palliative surgery (27+/-4 days vs 10+/-5 days; p < 0.05). in PD patients the morbidity rate was 22,72 % and the mortality rate 4.5%. CONCLUSIONS: In recent years laparoscopic surgery has become very important in oncologic surgery because it is minimally invasive and reduces postoperative complications and because there is sufficient evidence based data showing that results in terms of complications and survival are as good as the results of conventional surgery. However the learning curve for laparoscopic cancer surgery of the head of the pancreas is steep and our results indicate that in LPD operative time is significantly longer than in PD, and moreover the laparoscopic approach is not associated with a shorter hospital stay. Therefore LPD should be performed only in well-established laparoscopic and oncological centers with a multidisciplinary team. KEY WORDS: Laparoscopy, Pancreatic cancer, Pancreaticoduodenectomy. PMID- 26898784 TI - Graphene oxide-assisted non-immobilized SELEX of okdaic acid aptamer and the analytical application of aptasensor. AB - Okadaic acid (OA) is a low-molecular-weight marine toxin from shellfish that causes abdominal pain, vomiting and diarrhea, i.e., diarrheic shellfish poisoning. In this study, a ssDNA aptamer that specifically binds to OA with high affinity was obtained via Systematic Evolution of Ligands by Exponential Enrichment (SELEX) assisted by graphene oxide (GO). This aptamer was then applied to fabricate a novel direct competitive enzyme-linked aptamer assay (ELAA). At the optimized conditions, this ELAA method showed a low detection limit (LOD of 0.01 ng/mL), wide linear range (from 0.025 to 10 ng/mL), good recovery rate (92.86-103.34% in OA-spiked clam samples) and repeatability (RSD of 2.28-4.53%). The proposed method can be used to detect OA in seafood products with high sensitivity and can potentially be adapted for the determination of other small molecular analytes. PMID- 26898786 TI - [Population colorectal cancer screening in the Czech Republic]. AB - Colorectal cancer (CRC) is the third most common malignant disease in developed countries and its incidence is steadily growing. This trend has a stable character despite the fact that CRC is among the best prevention influenced malignancies. National CRC screening program in the Czech Republic, which was established in year 2000, follows the world trends resulting from evidence based medicine. Currently, the basic tools of screening program are immunochemical fecal occult blood tests and colonoscopy in case of their positivity or screening colonoscopy. Stagnation of participating population resulted to initiation of address invitation of the target population in January 2014, in which citizens are regularly invited to attend the screening program and their response is subsequently evaluated. Screening that impacts whole target group is called population screening. KEY WORDS: colorectal cancer, population screening program, colonoscopy, fecal occult blood tests, address invitation. PMID- 26898787 TI - [Novel imaging methods in endoscopic diagnosis of gastrointestinal tumors]. AB - Advances in imaging, digitization and all kinds of technologies result in development of potentially efficient imaging modalities, which enable magnification to subcellular levels, color differentiation and observation of pathophysiological processes. NBI, FICE, I-scan and KFE are new commercially available modalities.NBI is the most explored one. Its contribution has been shown in diagnosis of Barrett's neoplasia and esophageal squamous cell carcinoma and in characterization of early stomach cancer. It enables rather accurate characterization of changes in adenomatous colonic polyps; however it is not used for this purpose in clinical practice. It can demonstrate atrophy of small bowel mucosa in celiac disease, but it is not able to evaluate intraepithelial lymphocytosis. Its contribution in dysplasia detection in inflammatory bowel disease is not significant; chromoendoscopy remains the gold standard.The use of CFE remains experimental; the routine use is limited also due to its high cost. PMID- 26898788 TI - [Foregut diseases: foregut neoplasms]. AB - The diseases esophagus, stomach and duodenum are more frequently described as the foregut diseases. This term arises from the common embryologic origin of this part of the gastrointestinal (GI) tract. Therefore similar diagnostic approach, surgical therapy and possible secondary prevention are recommended.The concept of foregut surgery has been used for many years in USA and western countries mainly among surgeons and gastroenterologist, especially i the management of patients with upper GI tract malignancies.In the Czech Republic, there were 2,204 patients diagnosed yearly with foregut cancers in years 2006-2010. These carcinomas are the second most common solid GI malignancies, following colorectal cancer (8,127 yearly). Among all cancers they occupy the fourth position in incidence after colorectal cancer, breast cancer (6,371 yearly) and lung cancer (6,782 yearly). Regarding the numbers of surgically treated cancers, they rank the third position. The late clinical stage diagnosis is associated with low five year survival (18 % esophagus; 30 % stomach).Therefore, it is necessary to search for better early endoscopic diagnosis. In case of surgery, the improvement is possible by using the high volume hospitals principle. PMID- 26898789 TI - [Malignant biliary obstruction]. AB - Pancreatic cancer and cholangiocarcinoma are the most common causes of malignant biliary obstruction. They are diseases of increasing incidence and unfavorable prognosis. Only patients with localized disease indicated for surgery have a chance of long-term survival. These patients represent less than 20 % of all patients, despite the progress in our diagnostic abilities.Locally advanced and metastatic tumors are treated with palliative chemotherapy or chemoradiotherapy; the results of such treatments are unsatisfactory. The average survival of patients with unresectable disease is 6 months and only 5-10 % of patients survive 5 years.Biliary drainage is an integral part of palliative treatment. Endoscopically or percutaneosly placed stents improve quality of life, decrease cholestasis and pruritus, but do not significantly improve survival. Biliary stents get occluded over time, possibly resulting in acute cholangitis and require repeated replacement.Photodynamic therapy and radiofrequency ablation, locally active endoscopic methods, have been increasingly used in recent years in palliative treatment of patients with malignant biliary obstruction. In photodynamic therapy, photosensitizer accumulates in tumor tissue and is activated 48 hours later by light of a specific wave length. Application of low voltage high frequency current during radiofrequency ablation results in tissue destruction by heat. Local ablation techniques can have a significant impact in a large group of patients with malignant biliary obstruction, leading to improved prognosis, quality of life and stent patency. PMID- 26898790 TI - [Pancreatic cancer - current effective diagnostic and therapeutic approach]. AB - Pancreatic cancer is solid malignant, chemoresistant tumour with unfavourable prognosis. Radical resection with adjuvant chemotherapy is only potential curable therapeutic modality enabling to prolong survival of 20 % patients. Borderline conception contents active approach to primary non-resectable patients to reach resectability by neoadjuvant chemo(radio)therapy. Palliative and symptomatic therapy is indicated in about 70 % patients.In the case of suspicious of pancreatic cancer, patient should be referral to specialized centre. Effective diagnostic therapeutic approach only guarantees optimal quality of life of these patients. KEY WORDS: pancreatic cancer - diagnosis and therapy, multidisciplinary approach, quality of life. PMID- 26898791 TI - [Early detection of sporadic pancreatic cancer]. AB - Pancreatic cancer (PC) behaves very differently in comparison with other malignancies. Its prevalence continuously increases, mortality does not decrease, diagnosis is frequently late, radical surgery is limited to 15-20 % of patients, postoperative relapses are frequent, and chemotherapy has a palliative character. Preventive programs are the only possibility of improvement. In familial pancreatic cancer (FPC) the knowledge of the genetic mutation enables earlier entry of specialists into the surveillance program. The repeated use of high resolution imaging methods (including endoscopy and pancreatic cytology) may be followed by more frequent detection of the precursors and earlier stages of FPC. The identification of sporadic pancreatic cancer (SPC) depends fully on the construction of a multi-step and multi-disciplinary preventive program. PMID- 26898792 TI - [KRAS mutation assay on EUS-FNA specimens from pacients with pancreatic mass]. AB - Differential diagnosis of solid pancreatic masses using EUS FNA is in 1015 % of cases still challenging. Promising method, which helps to distinguish between chronic pancreatitis and cancer, is point mutations of the proto-oncogene KRAS test. This method is not established in routine clinical practice yet.Objectives were the determination of the sensitivity of the KRAS assay using various kinds of samples of patients with pancreatic mass and testing the effect of the presence of KRAS mutations on the prognosis of survival. 147 patients underwent EUS-FNA examination of pancreatic mass, accompanied by blood sampling with subsequent separation of plasma for the detection of circulating tumor DNA. Part of biopsy sample was left native in a stabilizing solution and part as cytological smear. Samples (native aspirates, cytological smears, plasma) were examined for the presence of KRAS mutation by heteroduplex analysis, denaturing capillary electrophoresis.Among 147 patients with pancreatic masses, 118 were diagnosed as a cancer, 26 chronic pancreatitis, 3 neuroendocrine tumor. In total 147 native aspirates, 118 cytological smears and 94 plasma samples were examined. The highest sensitivity of KRAS mutation was reached in the group of pancreatic cancer patients using cytology, in which 90 % of KRAS mutation was detected (106/118 of the samples). When using the native cellular aspirates, mutation was detected in 78 % (92/118 samples), and examination of plasma was positive in 27 % (24/90 samples). In four patients with chronic pancreatitis KRAS mutations was detected, although none has been cytologically confirmed as a cancer. Two of these four patients were confirmed in the course of the disease as a cancer, one patient died because of alcoholic delirium and the last one was indicated for surgery recently.Examination of KRAS mutations can be performed in all patients undergoing EUS-FNA, with the cytology being the most reliable type of sample for genetic tests. KRAS examination would be reasonable to introduce into routine clinical practice in a group of patients with unclear differential diagnosis of chronic pancreatitis, especially in those with suspicion of cancer in inflammatory terrain.Kexwords: pancreatic cancer, chronic pancreatitis, KRAS mutation , EUS-FNA. PMID- 26898793 TI - [ART score prognostic significance in patients with intermediate hepatocellular carcinoma]. AB - Palliative transarterial chemoembolization is indicated for patients with stage B hepatocellular carcinoma (HCC) based on the Barcelona Clinic Liver Cancer classification (BCLC). As this is a very wide and heterogenous group of patients, the ART score was designed to better differentiate these patients and to guide the decision for a second transarterial chemoembolization cycle.The goal of the study is to prove that the ART score is appropriate to define subgroups within the stage BCLC-B HCC group with significantly better or worse overall survival (OS) after repeated transarterial chemoembolization. A combined retrospective and prospective study was performed of the OS of patients with stage BCLC-B HCC that were monitored and treated at the Internal Medicine Clinic of the First Faculty of Medicine, Charles University in Prague and the Central Military Hospital Prague. An analysis of the survival curve using the Kaplan-Meier method was performed using the R software package.The median OS of the entire patient group was 18 months (95% CI 12-33). The median OS of patients with a favorable ART score was 33 months (95% CI 12-33) compared to 12 months (95% CI 6-18) for patients with an unfavorable ART score. The difference in OS in the subgroups differentiated by ART score was statistically significant (p < 0.01). Due to the significant difference in OS of patients differentiated by ART score, the currently recommended guidelines for the treatment of patients with stage BCLC-B hepatocellular carcinoma should be revised. PMID- 26898794 TI - What is the Nature of a Post-Materialist Paradigm? Three Types of Theories. AB - What does it mean to have a post-materialist theory? I propose that there are three classes or categories of theories. (1) Type I post-materialist theories: neo-physical theories that are derived from materialist theories, where the materialist theories are still seen as primary and are viewed as being fundamentally necessary to create "non-material" (yet physical) phenomena such as consciousness. (2) Type II post-materialist theories: post-materialist theories of consciousness existing alongside materialist theories, where each class of theories are seen as primary and are viewed as not being derivable from (i.e. are not reducible to) the other And (3) Type I post-materialist theories: where materialist theories are derived from, and are a subset of, more inclusive post materialist theories of consciousness; here post-materialist theories are seen as primary and are viewed as the ultimate origin of material systems. Type I theories are the least controversial, Type III are the most controversial. The three types of theories are considered in the context of the history of the emergence of post-materialist science. PMID- 26898795 TI - Characteristic phasic evolution of convulsive seizure in PCDH19-related epilepsy. AB - PCDH19-related epilepsy is a genetic disorder that was first described in 1971, then referred to as "epilepsy and mental retardation limited to females". PCDH19 has recently been identified as the responsible gene, but a detailed characterization of the seizure manifestation based on video-EEG recording is still limited. The purpose of this study was to elucidate features of the seizure semiology in children with PCDH19-related epilepsy. To do this, ictal video-EEG recordings of 26 convulsive seizures in three girls with PCDH19-related epilepsy were analysed. All seizures occurred in clusters, mainly during sleep accompanied by fever. The motor manifestations consisted of six sequential phases: "jerk", "reactive", "mild tonic", "fluttering", "mild clonic", and "postictal". Some phases were brief or lacking in some seizures, whereas others were long or pronounced. In the reactive phase, the patients looked fearful or startled with sudden jerks and turned over reactively. The tonic and clonic components were less intense compared with those of typical tonic-clonic seizures in other types of epilepsy. The fluttering phase was characterised initially by asymmetric, less rhythmic, and less synchronous tremulous movement and was then followed by the subtle clonic phase. Subtle oral automatism was observed in the postictal phase. The reactive, mild tonic, fluttering and mild clonic phases were most characteristic of seizures of PCDH19-related epilepsy. Ictal EEG started bilaterally and was symmetric in some patients but asymmetric in others. It showed asymmetric rhythmic discharges in some seizures at later phases. The electroclinical pattern of the phasic evolution of convulsive seizure suggests a focal onset seizure with secondary generalisation. Based on our findings, we propose that the six unique sequential phases in convulsive seizures suggest the diagnosis of PCDH19-related epilepsy when occurring in clusters with or without high fever in girls. [Published with video sequences online]. PMID- 26898796 TI - The roles of p62/SQSTM1 on regulation of matrix metalloproteinase-9 gene expression in response to oxLDL in atherosclerosis. AB - OBJECTIVE: Matrix metalloproteinase-9 (MMP-9) plays an important role in the remodeling of the extracellular matrix in atherosclerosis plaques. Autophagy protects macrophages against the processes of vascular disease. Our research explores how autophagy plays roles in macrophages to secret MMP-9. METHODS AND RESULTS: In response to increased doses of oxLDL or CQ we monitored the autophagic flux. Our results revealed that oxLDL was dynamically associated with autophagy and 100 MUg/ml oxLDL blocked autophagic flux in THP-1 cells. Moreover p62/SQSTM1 knocking down and CQ respectively inhibited and increased MMP-9 transcriptional expression. These effects were mediated by inhibition of NF kappaB. CONCLUSION: Abundant oxLDL blocked autophagic flux resulting in the aggregation of p62/SQSTM1. Then p62/SQSTM1 was involved in gene expression of MMP 9 via NF-kappaB-dependent signaling, and thus featuring novel plaque vulnerability properties of the atherosclerotic plaque. Understanding the mechanism that selectively modulates p62/SQSTM1 will provide a novel strategy for anti-atherogenesis. PMID- 26898798 TI - The dynamics of histone H2A ubiquitination in HeLa cells exposed to rapamycin, ethanol, hydroxyurea, ER stress, heat shock and DNA damage. AB - Polyubiquitination plays key roles in proteasome-dependent and independent cellular events, whereas monoubiquitination is involved in gene expression, DNA repair, protein-protein interaction, and protein trafficking. We previously developed an FK2 antibody, which specifically recognizes poly-Ub moieties but not free Ub. To elucidate the role of Ub conjugation in response to cellular stress, we used FK2 to investigate whether chemical stress (rapamycin, ethanol, or hydroxyurea), ER stress (thapsigargin or tunicamycin), heat shock or DNA damage (H2O2 or methyl methanesulfonate) affect the formation of Ub conjugates including histone H2A (hH2A) ubiquitination. First, we found that all forms of stress tested increased poly-ubiquitinated proteins in HeLa cells. Furthermore, rapamycin and hydroxyurea treatment, and ER stress increased ubiquitination of hH2A, while methyl methanesulfonate (MMS) treatment induced deubiquitination of hH2A. The ethanol and H2O2 treatments, and heat shock transiently induced hH2A de ubiquitination, although deubiquitinated hH2A were ubiquitinated again by subsequent cultivation. We also revealed that FK2 reacts with not only polyubiquitinated proteins but also mono-ubiquitinated hH2A. With the exception of MMS, all forms of stress tested increased the acetylation of K5-hH2A, K9-hH3 and K8-hH4 in addition to ubiquitination. K118 and K119 of hH2A were ubiquitinated in cells under normal conditions, and K119 was the major ubiquitination site. The MMS-treatment and heat shock induced the deubiquitination of both K118 and K119-histone H2A. Interestingly, MMS treatment did not affect cell HeLa cell viability expressing double-mutant hH2A (KK118,119AA-hH2A), while heat shock slightly but significantly decreased viability of double-mutant hH2A expressing cells, indicating that ubiquitination of both sites associates with recovery from heat shock but not MMS treatment. Thus, we characterized FK2 reactivity and demonstrated that various stresses alter the ubiquitination status, particularly ubiquitinated hH2A and with histone acetylation, and highlight the physiological importance of hH2A ubiquitination after exposure to stress stimuli. PMID- 26898797 TI - MicroRNA-9 inhibits hyperglycemia-induced pyroptosis in human ventricular cardiomyocytes by targeting ELAVL1. AB - Diabetic cardiomyopathy is a common complication in patients with diabetes and is associated with underlying chronic inflammation and cardiac cell death, subsequently leading to heart failure (HF). ELAV-like protein 1 (ELAVL1) plays a critical role in the progression of inflammation and HF. However the role of ELAVL-1 in inflammation induced cardiac cell death (pyroptosis) under hyperglycemic condition remains elusive. Our data demonstrates that ELAVL1 expression augmented with a concomitant increase in caspase-1 and IL-1 beta expression in human hearts and human ventricular cardiomyocytes under hyperglycemic condition. Furthermore, ELAVL1 knockdown abrogates TNF-alpha induced canonical pyroptosis via NLRP3, caspase-1 and IL-1beta suppression. Bioinformatics analysis and target validation assays showed that miR-9 directly targets ELAVL1. Interestingly, miRNA-9 expression significantly reduced in high glucose treated cardiomyocytes and in human diabetic hearts. Inhibition of miR-9 upregulates ELAVL1 expression and activates caspase-1. Alternatively, treatment with miR-9 mimics attenuates hyperglycemia-induced ELAVL1 and inhibits cardiomyocyte pyroptosis. Taken together our study highlights the potential therapeutic implications of targeting miR-9/ELAVL1 in preventing cardiomyocyte cell loss during HF in diabetics. PMID- 26898799 TI - SMIFH2-mediated mDia formin functional inhibition potentiates chemotherapeutic targeting of human ovarian cancer spheroids. AB - Due to a lack of effective screening or prevention protocol for epithelial ovarian cancer (EOC), there is a critical unmet need to develop therapeutic interventions for EOC treatment. EOC metastasis is unique. Initial dissemination is not primarily hematogenous, yet is facilitated through shedding of primary tumor cells into the peritoneal fluid and accumulating ascites. Increasingly, isolated patient spheroids point to a clinical role for spheroids in EOC metastasis. EOC spheroids are highly invasive structures that disseminate upon peritoneal mesothelium, and visceral tissues including liver and omentum. Selection for this subset of chemoresistant EOC cells could influence disease progression and/or recurrence. Thus, targeting spheroid integrity/structure may improve the chemotherapeutic responsiveness of EOC. We discovered a critical role for mammalian Diaphanous (mDia)-related formin-2 in maintaining EOC spheroid structure. Both mDia2 and the related mDia1 regulate F-actin networks critical to maintain cell-cell contacts and the integrity of multi-cellular epithelial sheets. We investigated if mDia2 functional inhibition via a small molecule inhibitor SMIFH2 combined with chemotherapeutics, such as taxol and cisplatin, inhibits the viability of EOC monolayers and clinically relevant spheroids. SMIFH2-mediated mDia formin inhibition significantly reduced both ES2 and Skov3 EOC monolayer viability while spheroid viability was minimally impacted only at the highest concentrations. Combining either cisplatin or taxol with SMIFH2 did not significantly enhance the effects of either drug alone in ES2 monolayers, while Skov3 monolayers treated with taxol or cisplatin and SMIFH2 showed significant additive inhibition of viability. ES2 spheroids were highly responsive with clear additive anti-viability effects with dual taxol or cisplatin when combined with SMIFH2 treatments. While combined taxol with SMIFH2 in spheroids showed an additive effect relative to single treatments, Skov3 spheroids showed no additive effects from combined cisplatin and SMIFH2 treatments. Our data indicate that mDia formin inhibition combined with taxol to drive enhanced and/or additive anti-viability effects targeting 3D EOC structures, including ES2 and Skov3 spheroids. Combined mDia formin inhibition with cisplatin may be most effective in EOC spheroids where cisplatin sensitivity is retained at moderate levels, such as ES2 cells. PMID- 26898800 TI - A bispecific antibody (ScBsAbAgn-2/TSPO) target for Ang-2 and TSPO resulted in therapeutic effects against glioblastomas. AB - Antibody-based targeted therapy of cancers requires the antibody targeting of specific molecules inducing tumor cells apoptosis or death. Angiopoietin-2 (Agn 2) and translocator protein (TSPO) are identified as potential target molecules for glioblastoma therapy. The single chain anti-Agn-2 antibody (Anag-2) and anti TSPO antibody (ATSPO) were obtained by monoclonal antibody screening. In the present study, for specific targeting and killing, we generated a recombinant bispecific antibody comprising a single-chain Fragment variable (ScFv) of anti human Agn-2 and anti-human TSPO (ScBsAbAgn-2/TSPO), which is the mediator for mitochondrial apoptosis and tumor angiogenesis. In vitro, ScBsAbAgn-2/TSPO simultaneously bounded to both targets with a high antigen-binding affinity to Anag-2 and TSPO compared to the individual antibody. The higher expression of Ang 2 and TSPO was observed in bevacizumab-treated glioblastoma compared to normal rat brain endothelium. We also observed apoptosis-mediated cytotoxicity was improved, which resulted in the elimination of up to 90% of the target cells within 72 h. ScBsAbAgn-2/TSPO inhibited tumor growth, decreased vascular permeability, led to extended survival, improved pericyte coverage, depletion of tumor-associated macrophages, and increased numbers of intratumoral T lymphocytes infiltration in a murine bevacizumab-treated glioblastoma model. These findings were also confirmed ex vivo using glioblastoma cells from bevacizumab-treated rats with glioblastoma. We conclude that ScBsAbAgn-2/TSPO targeting of glioblastoma cell lines can be achieved in vitro and in vivo that the efficient elimination of glioblastoma cells supports the potential of ScBsAbAgn-2/TSPO as a potent, novel immunotherapeutic agent. PMID- 26898801 TI - Singlet oxygen generation during the oxidation of L-tyrosine and L-dopa with mushroom tyrosinase. AB - The generation of singlet oxygen during the oxidation of tyrosine and L-dopa using mushroom tyrosinase in a phosphate buffer (pH 7.4), the model of melanin synthesis in melanocytes, was examined. The reaction was performed in the presence of 2,2,6,6-tetramethyl-4-piperidone (4-oxo-TEMP), an acceptor of singlet oxygen and the electron spin resonance (ESR) of the spin adduct, 4-oxo-2,2,6,6 tetramethyl-1-piperidinyloxy (4-oxo-TEMPO), was measured. An increase in the ESR signal attributable to 4-oxo-TEMPO was observed during the oxidation of tyrosine and L-dopa with tyrosinase, indicating the generation of singlet oxygen. The results suggest that (1)O2 generation via tyrosinase-catalyzed melanin synthesis occurs in melanocyte. PMID- 26898802 TI - Ptpmt1 induced by HIF-2alpha regulates the proliferation and glucose metabolism in erythroleukemia cells. AB - Hypoxia provokes metabolism misbalance, mitochondrial dysfunction and oxidative stress in both human and animal cells. However, the mechanisms which hypoxia causes mitochondrial dysfunction and energy metabolism misbalance still remain unclear. In this study, we presented evidence that mitochondrial phosphatase Ptpmt1 is a hypoxia response molecule that regulates cell proliferation, survival and glucose metabolism in human erythroleukemia TF-1 cells. Exposure to hypoxia or DFO treatment results in upregulation of HIF1-alpha, HIF-2alpha and Ptpmt1. Only inhibition of HIF-2alpha by shRNA transduction reduces Ptpmt1 expression in TF-1 cells under hypoxia. Ptpmt1 inhibitor suppresses the growth and induces apoptosis of TF-1 cells. Furthermore, we demonstrated that Ptpmt1 inhibition reduces the Glut1 and Glut3 expression and decreases the glucose consumption in TF-1 cells. In additional, Ptpmt1 knockdown also results in the mitochondrial dysfunction determined by JC1 staining. These results delineate a key role for HIF-2alpha-induced Ptpmt1 upregulation in proliferation, survival and glucose metabolism of erythroleukemia cells. It is indicated that Ptpmt1 plays important roles in hypoxia-induced cell metabolism and mitochondrial dysfunction. PMID- 26898803 TI - An index predictive of cognitive outcome in retired professional American Football players with a history of sports concussion. AB - OBJECTIVE: Various concussion characteristics and personal factors are associated with cognitive recovery in athletes. We developed an index based on concussion frequency, severity, and timeframe, as well as cognitive reserve (CR), and we assessed its predictive power regarding cognitive ability in retired professional football players. METHOD: Data from 40 retired professional American football players were used in the current study. On average, participants had been retired from football for 20 years. Current neuropsychological performances, indicators of CR, concussion history, and play data were used to create an index for predicting cognitive outcome. RESULTS: The sample displayed a range of concussions, concussion severities, seasons played, CR, and cognitive ability. Many of the participants demonstrated cognitive deficits. The index strongly predicted global cognitive ability (R(2) = .31). The index also predicted the number of areas of neuropsychological deficit, which varied as a function of the deficit classification system used (Heaton: R(2) = .15; Wechsler: R(2) = .28). CONCLUSIONS: The current study demonstrated that a unique combination of CR, sports concussion, and game-related data can predict cognitive outcomes in participants who had been retired from professional American football for an average of 20 years. Such indices may prove to be useful for clinical decision making and research. PMID- 26898805 TI - Does cerebral vasoconstriction following delivery protect against hyperoxia? PMID- 26898804 TI - Manifestations and characteristics of congenital adrenal hyperplasia-associated encephalopathy. AB - BACKGROUND: This study aimed to clarify the characteristics of acute encephalopathic episodes in patients with congenital adrenal hyperplasia (CAH), which we termed "CAH-associated encephalopathy (CAHE)." METHODS: This retrospective study was conducted using a questionnaire as a nationwide survey of patients with CAH with acute encephalopathy and related episodes. RESULTS: Fifteen patients were recruited on the bases of clinical data that supported a diagnosis of CAHE. Fourteen patients displayed seizures at onset, and 12 patients exhibited refractory seizures. Deep coma lasting >24h was noted in 12 patients. Neuroimaging studies revealed some heterogeneous features. Diffuse or focal edematous lesions in the cerebrum, which produce high signal intensity on diffusion-weighted magnetic resonance imaging or low density on computer tomography, were found in the acute period in all 15 patients. In the chronic period, 14 patients survived, 11 of whom had some degree of neurological sequelae. Moreover, various degrees of cerebral shrinkage were observed in 11 of 14 surviving patients. Surprisingly, there were no abnormal neuroimaging findings in the basal ganglia, brainstem, and cerebellum in any patient. CONCLUSION: Our results indicated that patients with CAH have a risk of developing CAHE, and thus, they should be followed closely because not only status epilepticus or deep coma but also minor symptoms, such as fever and nausea, may lead to CAHE. Because CAHE may feature some heterogeneous encephalopathic episodes, further validation is needed to clarify its etiology. PMID- 26898806 TI - Caffeine Exposure and Risk of Acute Kidney Injury in a Retrospective Cohort of Very Low Birth Weight Neonates. AB - OBJECTIVE: To evaluate the association between caffeine exposure and acute kidney injury (AKI) in very low birth weight (VLBW; <=1500 g) neonates. STUDY DESIGN: We retrospectively reviewed a cohort of 140 VLBW neonates consecutively admitted to the University of Virginia's neonatal intensive care unit from March 2011 to June 2012, excluding only those admitted >2 days of age or who died at <2 days after birth. We separately analyzed a subgroup of 44 neonates who received prolonged invasive respiratory support (mechanical ventilation for first 7 days after birth). The exposure of interest was caffeine exposure in the first week after birth. The primary outcome was AKI within the first 10 days after birth according to the Kidney Disease: Improving Global Outcomes system, modified to include only serum creatinine. RESULTS: Caffeine exposure occurred in 72.1% of all patients and 54.5% of those who received prolonged invasive respiratory support. AKI occurred less frequently in neonates who received caffeine (all patients: 17.8% vs 43.6%; P = .002; prolonged invasive respiratory support: 29.2% vs 75.0%; P = .002). Caffeine exposure was associated with decreased odds for AKI in logistic regression models adjusted for sex, birth weight, gestational age, small for gestational age status, illness severity on admission, and receipt of indomethacin, invasive ventilation, dopamine, aminoglycosides, and vancomycin (all patients: OR 0.22; 95% CI 0.07-0.75, P = .02; prolonged invasive respiratory support subgroup: OR 0.06; 95% CI 0.01-0.57, P = .02). CONCLUSIONS: In a cohort of VLBW neonates, those exposed to caffeine were less likely to experience AKI. PMID- 26898807 TI - Comparable Survival of En Bloc versus Standard Donor Kidney Transplants in Children. AB - OBJECTIVE: To determine whether renal transplantation survival is similar in children receiving pediatric en bloc kidneys compared with those receiving standard deceased donor kidneys. STUDY DESIGN: We compared time to allograft failure and estimated glomerular filtration rate (eGFR) in pediatric recipients of en bloc and standard criteria deceased donor renal transplants using Organ Procurement and Transplantation Network data for 2000-2013. Cox regression analysis was used to compare time to allograft failure, and the Student t test was used to compare eGFR. RESULTS: A total of 6882 recipients met the study inclusion criteria; 1.8% received an en bloc transplant. The adjusted hazard for allograft failure was similar for recipients of en bloc kidneys compared with standard criteria kidneys (hazard ratio, 1.15; 95% CI, 0.83-1.59; P = .41). The median wait time for transplantation was significantly shorter for recipients of en bloc kidneys (157 days vs 208 days; P = .03). Moreover, eGFR was superior for recipients of en bloc kidneys up to 5 years post-transplantation. CONCLUSION: Transplantation of en bloc pediatric kidneys should be considered a viable option for pediatric recipients and may afford unique benefits by reducing wait times and promoting preservation of graft function. PMID- 26898808 TI - Failure to Thrive and Bilateral Periorbital Ecchymosis. PMID- 26898809 TI - Diagnosing Jaundice by Eye-Outpatient Assessment of Conjunctival Icterus in the Newborn. AB - In pediatric office practices, we compared transcutaneous bilirubin levels in 689 newborns, age 3-10 days, with and without conjunctival icterus. In this age range, and in the absence of other clinical or laboratory indications, the presence of conjunctival icterus does not imply the need to measure the transcutaneous bilirubin or serum bilirubin level, but the absence of conjunctival icterus helps to rule out significant hyperbilirubinemia. PMID- 26898810 TI - Reply. PMID- 26898811 TI - Reversing the mere exposure effect in spider fearfuls: Preliminary evidence of sensitization. AB - A mere exposure effect (MEE) is said to occur when individuals' liking of a suboptimally and repeatedly presented stimulus increases compared to never presented stimuli, while they are unable to indicate which stimuli were previously presented and which were not. In two experiments, we used the MEE to study automatic evaluative processes in highly spider-fearful individuals (SFs). Pictures of spiders and butterflies were repeatedly presented suboptimally to SFs and to non-anxious controls (NACs). In Experiment 1, both groups showed the MEE for butterflies, preferring previously presented butterfly pictures over new ones. For spider pictures, only NACs showed an MEE, whereas SFs showed no preference. Experiment 2 involved a more unpleasant presentation situation, because for each picture, participants had the difficult task to indicate what had been presented to them. This led to a reversed MEE for spiders in SFs: They preferred new spider pictures over previously presented ones. In both experiments, no evidence was observed for the ability to differentiate between old an new pictures. The results are tentatively explained within Zajonc' theory of the MEE, and they are related to the concept of sensitization in anxiety disorders. PMID- 26898812 TI - Ammonium tetrathiomolybdate as a water-soluble and slow-release hydrogen sulfide donor. AB - Ammonium tetrathiomolybdate (TTM) was found to be a slow hydrogen sulfide (H2S) releasing agent. Its H2S generation capability in aqueous solutions was confirmed by UV-vis and fluorescence assays. TTM also showed H2S-like cytoprotective effects in hydrogen peroxide (H2O2)-induced oxidative damage in HaCaT cells. PMID- 26898813 TI - New orally active diphenylmethyl-based ester analogues of dihydroartemisinin: Synthesis and antimalarial assessment against multidrug-resistant Plasmodium yoelii nigeriensis in mice. AB - A new series of ester analogues of artemisinin 8a-f, incorporating diphenylmethyl as pharmacologically privileged substructure, and 8g-j have been prepared and evaluated for their antimalarial activity against multidrug-resistant (MDR) Plasmodium yoelii nigeriensis in Swiss mice via oral route. These diphenylmethyl based ester analogues 8a-f were found to be 2-4 folds more active than the antimalarial drugs beta-arteether 4 and artesunic acid 5. Ester 8a, the most active compound of the series, provided complete protection to the infected mice at 24 mg/kg * 4 days as well as 12 mg/kg * 4 days, respectively. In this model beta-arteether provided 100% and 20% protection at 48 mg/kg * 4 days and 24 mg/kg * 4 days, respectively. PMID- 26898816 TI - Marjolin's Ulcer Complicating a Pressure Sore: The Clock is Ticking. AB - BACKGROUND: Malignant degeneration in any chronic wound is termed a Marjolin's ulcer (MU). The overall metastatic rate of MU is approximately 27.5%. However, the prognosis of MU specific to pressure sores is poor, with a reported metastatic rate of 61%. This is due to insidious, asymptomatic malignant degeneration, a lack of healthcare provider awareness, and, ultimately, delayed management. CASE REPORT: An 85-year-old white male was noted by his wound-care nurse to have a rapidly developing growth on his lower back over a period of 4 months. There was history of a non-healing, progressive pressure ulcer of the lower back for the past 10 years. On examination, there was a 4 * 4 cm pressure ulcer of the lower back, with a superimposed 1.5 * 2 cm growth in the superior region. There was an absence of palpable regional lymphadenopathy. Punch biopsy revealed squamous cell carcinoma consistent with Marjolin's ulcer. The ulcer underwent excision with wide margins, and a skin graft was placed. Due to the prompt recognition of an abnormality by the patient's wound-care nurse, metastasis was not evident on imaging. There are no signs of recurrence at 1-year follow-up. CONCLUSIONS: Marjolin's ulcer has a rapid progression from local disease to widespread metastasis. Therefore, it is essential that wound-care providers are aware of the clinical signs and symptoms of malignant degeneration in chronic wounds. PMID- 26898817 TI - Commentary on 'Predictors of 1 Year Survival After Endovascular Aneurysm Repair'. PMID- 26898815 TI - Novel antibody drug conjugates containing exatecan derivative-based cytotoxic payloads. AB - Trastuzumab conjugates consisting of exatecan derivatives were prepared and their biological activities and physicochemical properties were evaluated. The ADCs showed strong efficacy and a low aggregation rate. The exatecan derivatives were covalently connected via a peptidyl spacer (Gly-Gly-Phe-Gly), which is assumed to be stable in circulation, and were cleaved by lysosomal enzymes following ADC internalization into tumor tissue. These anti-HER2 ADCs exhibited a high potency, specifically against HER2-positive cancer cell lines in vitro. The ADCs, bearing exatecan derivatives which have more than two methylene chains, exhibited superior cytotoxicity. It was speculated that steric hindrance of the cleavable amide moiety could be involved in the drug release. The adequate alkyl lengths of exatecan derivatives (13, 14, 15) were from two to four in terms of aggregation rate. The ADC having a hydrophilic moiety showed good efficacy in a HER2-positive and Trastuzumab-resistant breast carcinoma cell model in mice. PMID- 26898814 TI - SAR exploration at the C-3 position of tetrahydro-beta-carboline sstr3 antagonists. AB - MK-4256, a tetrahydro-beta-carboline sstr3 antagonist, was discontinued due to a cardiovascular (CV) adverse effect observed in dogs. Additional investigations revealed that the CV liability (QTc prolongation) was caused by the hERG off target activity of MK-4256 and was not due to sstr3 antagonism. In this Letter, we describe our extensive SAR effort at the C3 position of the tetrahydro-beta carboline structure. This effort resulted in identification of 5-fluoro-pyridin-2 yl as the optimal substituent on the imidazole ring to balance sstr3 activity and the hERG off-target liability. PMID- 26898819 TI - Influence of home care services on caregivers' burden and satisfaction. AB - AIMS AND OBJECTIVES: To examine the factors affecting the burden and satisfaction of family caregivers, focusing on the beneficial impacts of home care service use. BACKGROUND: Long-term care for older patients is a multifaceted process that brings both burden and satisfaction to family caregivers. It is expected that home care services offered by the Korean long-term care insurance may contribute to decreasing the burden of family caregivers and enhancing their satisfaction by assisting with practical caregiving tasks. DESIGN: A cross-sectional study. METHODS: A convenience sample of 157 family caregivers was recruited from five home care service agencies in South Korea. Information about the caregivers, caregiving history, older care recipients and use of home care services was assessed. The effects of home care service use on caregiving burden and satisfaction were tested using hierarchical multiple regression analyses after adjusting for the characteristics of the caregivers, caregiving history and older care recipients. RESULTS: There was no significant influence of home care service use on reducing caregiving burden or on increasing caregivers' satisfaction. Although several factors were associated with caregiving burden and satisfaction, family functioning was the most unique factor to significantly affect both caregiving burden and satisfaction. CONCLUSIONS: Home care services might not automatically have a positive impact on caregivers' burden and satisfaction, but maintaining healthy family functioning is an important issue for family caregivers. The findings highlight the important need to reconsider ways to provide home care services and to develop nursing interventions to reinforce supportive family functioning. RELEVANCE TO CLINICAL PRACTICE: Practical strategies for providing home care services should be developed through a concrete assessment of the family dynamics and the needs of family caregivers. Health professionals should play a pivotal role in performing the assessment and in developing interventions to strengthen supportive family functioning. PMID- 26898818 TI - Examining the Impact of Latino Nativity, Migration, and Acculturation Factors on Colonoscopy Screening. AB - Latinos are a diverse population comprised of multiple countries of origin with varying cultural profiles. This study examines differences in colonoscopy completion across place of birth and migration-related factors in a sample of predominantly Dominican and Puerto Rican Latinos living in New York City after receiving a recommendation for colonoscopy screening and navigation services. The sample included 702 Latinos recruited for two cancer screening projects targeting Latinos eligible for colonoscopy who seek healthcare in New York City. Participants completed a survey that included sociodemographic, health-related questions, psychosocial assessments and cancer screening practices, in Spanish or English. Migration, acculturation, and language factors were found to predict colonoscopy completion. The results indicated that Latinos born in the Dominican Republic and Central America were more likely to complete a screening colonoscopy than their counterparts born in the US. Further, those who emigrated at an older age, who have resided in the US for less than 20 years, preferred Spanish and those with lower US acculturation levels were also more likely to complete a screening colonoscopy. The findings suggest that Latinos who are less acculturated to the US are more likely to complete a screening colonoscopy after receiving a physician recommendation for colonoscopy screening. The results provide important information that can inform clinical practice and public health interventions. Continued attention to cultural and migration influences are important areas for cancer screening intervention development. PMID- 26898820 TI - Primary tooth size asymmetry in twins and singletons. AB - OBJECTIVES: To explore asymmetry values of antimeric deciduous tooth crown dimensions in three types of twins: monozygotic (MZ), dizygotic same-sex (DZ) and opposite-sex (OS) vs. single-born controls. SETTING AND SAMPLE POPULATION: Mesiodistal and labio-lingual crown dimensions of second deciduous molars and mesiodistal canine and first molar crown dimensions of 2159 children at 6-12 years of age were evaluated, originating from the US cross-sectional Collaborative Perinatal Study from the 1970s, including altogether MZ (n = 28), DZ same-sex (n = 33) and OS (n = 39) pairs. Single born (n = 1959) were used as controls. MATERIAL AND METHODS: Dental casts were measured for comparison of variance relationships calculated from antimeric teeth, exhibiting fluctuating (FA), and directional (DA) asymmetry using anova. RESULTS: Significant differences appeared in MZ and OS girls in DA of deciduous canines, which gain size in the first and second trimester, and deciduous second molars, which finally stop crown growth during the early post-natal period. Significantly, increased FA values appeared for lower deciduous canines and second molars, indicating greatest environmental stress in OS girls, MZ girls and DZ boys. Twin girls had more fluctuating and directional crown asymmetry than twin boys, but in some dimensions, the twins were more symmetric than controls. CONCLUSIONS: Transmembrane hormonal influence between opposite-sex twins, and late gestational stress factors, caused by placental malfunction and/or monochorionicity, may be involved in asymmetric growth of antimers, during critical periods of crown size gain. PMID- 26898821 TI - Quality Measures at the Interface of Behavioral Health and Primary Care. AB - The development of quality measures has gained increasing attention as health care reimbursements transition from fee-for-service to value-based payment models. As behavioral health care moves towards integration of services with primary care, specific measures and payment incentives will be needed to successfully expand access. This study uses a keyword search to identify 730 quality indicators that are relevant to behavioral health and general medical health. Measures identified have been coded and grouped into domains based on a taxonomy developed by the authors. The analysis reveals that quality measures focusing on general medical conditions exceed those focused on behavioral health diagnoses for evidence-based treatments, patient safety, and outcomes. Furthermore, measures predominantly concentrate on care during or following hospitalizations, which represents a minority of behavioral health care and does not characterize the outpatient settings that are the focus of many models of integrated care. The authors offer recommendations for future steps to identify the quality measures that can best evaluate the evolving behavioral health care system. PMID- 26898822 TI - A systematic review and meta-analysis of comparative studies assessing the efficacy of luteinizing hormone-releasing hormone therapy for children with cryptorchidism. AB - PURPOSE: To assess the efficacy of intranasal luteinizing hormone-releasing hormone (LHRH) therapy for cryptorchidism. MATERIALS AND METHODS: Eligible studies were identified by two reviewers using PubMed, Embase, and Web of Science databases. Primary outcomes were complete testicular descent rate, complete testicular descent rate for nonpalpable testis, and pre-scrotal and inguinal testis. Secondary outcomes included testicular descent with different medicines strategy and a subgroup analysis. RESULTS: Pooled data including the 1255 undescended testes showed that complete testicular descent rate was 20.9 % in LHRH group versus 5.6 % in the placebo group, which was significantly different [relative risk (RR) 3.94, 95 % confidence interval (CI) 2.14-7.28, P < 0.0001]. There was also a significant difference in the incidence of pre-scrotal and inguinal position testis descent, with 22.8 % in the LHRH group versus 3.6 % in the placebo group (RR 5.79, 95 % CI 2.94-11.39, P < 0.00001). However, side effects were more frequent in the LHRH group (RR 2.61, 95 % CI 1.52-4.49, P = 0.0005). There were no significant differences for nonpalpable testes. CONCLUSIONS: LHRH had significant benefits on testicular descent, particularly for inguinal and pre-scrotal testes, which was also accompanied by temporary slight side effects. PMID- 26898823 TI - Effectiveness of a day care program in supporting patients on peritoneal dialysis and their caregivers. AB - PURPOSE: Physical inactivity and social isolation are major problems faced by peritoneal dialysis (PD) patients. Respite care is also an unmet need for their caregivers. The study aimed to evaluate the benefits of day care service for PD patients. METHOD: Khoo Teck Puat Hospital collaborated with St Luke's Eldercare (SLEC) to provide day care services for PD patients. The day care provided assistance with two PD exchanges and activities for patients to maintain health and improve social interaction. Outcome indicators included: (1) enrollment status, length of stay and peritonitis rate; (2) quality of life and mental status evaluations on patients and caregivers with the 12-item Short-Form Health Survey, Hospital Anxiety and Depression Scale and Zarit Burden Interview Short Form 12; and (3) qualitative data collected via interviews with patients, caregivers, healthcare providers and SLEC staff. RESULTS: Sixty-four patients were referred, and 16 eventually participated. Mean age of participants was 67.2 (range 54-85) years. For patients who stayed >1 month (n = 9), length of stay was 205.0 days (58-428) and frequency of attendance was 2.9 (0.6-4.8) times/week. There were no peritonitis episodes while patients were in the program. Mental improvement was noticed for most patients and caregivers, but physical improvement was less obvious. Caregivers also felt less burden. CONCLUSIONS: Day care service is effective in alleviating the burden of caregivers and beneficial to patients with relatively good functional status. However, persuading patients and their caregivers to take up the program was a challenge. PMID- 26898825 TI - Salvage of accidentally sectioned peritoneal dialysis catheters. PMID- 26898824 TI - Clinical imaging of vascular disease in chronic kidney disease. AB - Arterial wall calcification, once considered an incidental finding, is now known to be a consistent and strong predictor of cardiovascular events in patients with chronic renal insufficiency. It is also commonly encountered in radiologic examinations as an incidental finding. Forthcoming bench, translational, and clinical data seek to establish this and pre-calcification changes as surrogate imaging biomarkers for noninvasive prognostication and treatment follow-up. Emerging paradigms seek to establish vascular calcification as a surrogate marker of disease. Imaging of pre-calcification and decalcification events may prove more important than imaging of the calcification itself. Data-driven approaches to screening will be necessary to limit radiation exposure and prevent over utilization of expensive imaging techniques. PMID- 26898827 TI - Epigenetics: It's Getting Old. Past Meets Future in Paleoepigenetics. AB - Recent years have witnessed the rise of ancient DNA (aDNA) technology, allowing comparative genomics to be carried out at unprecedented time resolution. While it is relatively straightforward to use aDNA to identify recent genomic changes, it is much less clear how to utilize it to study changes in epigenetic regulation. Here we review recent works demonstrating that highly degraded aDNA still contains sufficient information to allow reconstruction of epigenetic signals, including DNA methylation and nucleosome positioning maps. We discuss challenges arising from the tissue specificity of epigenetics, and show how some of them might in fact turn into advantages. Finally, we introduce a method to infer methylation states in tissues that do not tend to be preserved over time. PMID- 26898826 TI - Compression of adjacent anatomical structures by pulmonary artery dilation. AB - Pulmonary hypertension is the commonest condition leading to dilated pulmonary artery. We describe three different types of compression of adjacent anatomical structures by dilated pulmonary arteries. We included involvement of the left main coronary artery, left recurrent laryngeal nerve and tracheobronchial tree. Compression of these structures can cause major complications such as myocardial ischemia, hoarseness and major airway stenosis. We present a case for each scenario and review the literature for each of these complications, focusing on patients' characteristics and contemporary management. PMID- 26898828 TI - Regulation of BRAF protein stability by a negative feedback loop involving the MEK-ERK pathway but not the FBXW7 tumour suppressor. AB - The (V600E)BRAF oncogenic mutation is detected in a wide range of human cancers and induces hyperactivation of the downstream MEK-ERK signalling cascade. Although output of the BRAF-MEK-ERK pathway is regulated by feed-forward RAF activity, feedback control also plays an important role. One such feedback pathway has been identified in Caenorhabditis elegans and involves ERK-mediated phosphorylation of BRAF within a CDC4 phosphodegron (CPD), targeting BRAF for degradation via CDC4 (also known as FBXW7), a component of the SKP1/CUL1/F-box (SCF) E3 ubiquitin ligase complex. Here we investigate this pathway in mammalian cells. Short-term expression of autochthonous (V600E)BRAF in mouse embryonic fibroblasts (MEFs) leads to down-regulation of BRAF protein levels in a proteasome-dependent manner and (V600E)BRAF has a reduced half-life compared to (WT)BRAF in HEK293(T) cells. These effects were reversed by treatment with the MEK inhibitor PD184352. We have identified the equivalent CPD at residues 400-405 in human BRAF and have found that mutation of ERK phosphorylation sites at residues T401 and S405 in (V600E)BRAF increases the half-life of the protein. While BRAF and FBXW7 co-immunoprecipitated, the overexpression of FBXW7 did not influence the half-life of either (WT)BRAF or (V600E)BRAF. Furthermore, disruption of the substrate-binding site of mouse FBXW7 using the R482Q mutation did not affect the interaction with BRAF and the expression levels of (WT)BRAF and (V600E)BRAF were not altered in MEFs derived from mice with the homozygous knockin (R482Q)FBXW7 mutation. Overall these data confirm the existence of a negative feedback pathway by which BRAF protein stability is regulated by ERK. However, unlike the situation in C. elegans, FBXW7 does not play a unique role in mediating subsequent BRAF degradation. PMID- 26898829 TI - PSD-95 regulates CRFR1 localization, trafficking and beta-arrestin2 recruitment. AB - Corticotropin-releasing factor (CRF) is a neuropeptide commonly associated with the hypothalamic-pituitary adrenal axis stress response. Upon release, CRF activates two G protein-coupled receptors (GPCRs): CRF receptor 1 (CRFR1) and CRF receptor 2 (CRFR2). Although both receptors contribute to mood regulation, CRFR1 antagonists have demonstrated anxiolytic and antidepressant-like properties that may be exploited in the generation of new pharmacological interventions for mental illnesses. Previous studies have demonstrated CRFR1 capable of heterologously sensitizing serotonin 2A receptor (5-HT2AR) signaling: another GPCR implicated in psychiatric disease. Interestingly, this phenomenon was dependent on Postsynaptic density 95 (PSD-95)/Disc Large/Zona Occludens (PDZ) interactions on the distal carboxyl termini of both receptors. In the current study, we demonstrate that endogenous PSD-95 can be co-immunoprecipitated with CRFR1 from cortical brain homogenate, and this interaction appears to be primarily via the PDZ-binding motif. Additionally, PSD-95 colocalizes with CRFR1 within the dendritic projections of cultured mouse neurons in a PDZ-binding motif dependent manner. In HEK 293 cells, PSD-95 overexpression inhibited CRFR1 endocytosis, whereas PSD-95 shRNA knockdown enhanced CRFR1 endocytosis. Although PSD-95 does not appear to play a significant role in CRF-mediated cAMP or ERK1/2 signaling, PSD-95 was demonstrated to suppress beta-arrestin2 recruitment: providing a potential mechanism for PSD-95's inhibition of endocytosis. In revisiting previously documented heterologous sensitization, PSD-95 shRNA knockdown did not prevent CRFR1-mediated enhancement of 5-HT2AR signaling. In conclusion, we have identified and characterized a novel functional relationship between CRFR1 and PSD-95 that may have implications in the design of new treatment strategies for mental illness. PMID- 26898830 TI - The characterisation of LATS2 kinase regulation in Hippo-YAP signalling. AB - By controlling the YAP1 proto-oncoprotein Hippo signalling plays important roles in cancer-associated processes. Current evidence suggests that the Hippo kinases MST1/2 together with the MOB1 scaffold protein promote the formation of active MOB1/LATS complexes which phosphorylate and thereby inhibit YAP1. However, the regulatory mechanisms of MST1/2-MOB1-LATS signalling are currently underinvestigated. Therefore, we studied LATS2 variants carrying specific modifications that mimic gain or loss of phosphorylation and/or abolish MOB1/LATS2 interactions. We discovered that Ser872 T-loop and Thr1041 hydrophobic motif (HM) phosphorylation of LATS2 is essential for LATS2 activation. MST1/2 phosphorylate LATS2 on Thr1041, but not Ser872, while MOB1 binding to LATS2 supports both phosphorylation events. Significantly, LATS2-PIF, a LATS2 variant containing the PRK2 HM, acts as a hyperactive LATS2 kinase that efficiently phosphorylates YAP1 and inhibits the transcriptional co-activity of YAP1. This inhibitory function of LATS2-PIF is dependent on LATS2 kinase activity, while MOB1/LATS2 and YAP1/LATS2 complex formation is dispensable, suggesting that elevated LATS2 kinase activity can be sufficient to oppose YAP1. Taken together, our characterisation of LATS2 variants uncovers novel insights into the regulation of LATS kinases in Hippo signalling. PMID- 26898831 TI - A deregulated expression of estrogen-target genes is associated with an altered response to estradiol in aged rats perinatally exposed to bisphenol A. AB - Here we assessed the effects of perinatal exposure to bisphenol A (BPA) on the uterine response to 17beta-estradiol (E2) in aged rats. Pregnant rats were orally exposed to 0.5 or 50 MUg BPA/kg/day from gestational day 9 until weaning. On postnatal day (PND) 360, the rats were ovariectomized and treated with E2 for three months. The uterine tissue of BPA50 and BPA0.5 rats showed increased density of glands with squamous metaplasia (GSM) and glands with daughter glands respectively. Wnt7a expression was lower in GSM of BPA50 rats than in controls. The expression of estrogen receptor 1 (ESR1) and its 5'- untranslated exons ESR1 O and ESR1-OT was lower in BPA50 rats. Both doses of BPA modified the expression of coactivator proteins and epigenetic regulatory enzymes. Thus, perinatal BPA exposed rats showed different glandular abnormalities associated with deregulated expression of E2-target genes. Different mechanisms would be involved depending on the BPA dose administered. PMID- 26898833 TI - First report of canine ocular thelaziosis in the Muntenia Region, Romania. AB - Ocular thelaziosis by Thelazia callipaeda is a vector-borne disease that infects domestic and wild carnivores as well as humans. In this paper, we present two cases of ocular thelaziosis in dogs that had never traveled outside Romania. Both presented with moderate conjunctivitis and ocular discharge. In total, 41 adult nematodes were removed from the conjunctival sacs of both dogs; these were identified via morphology as T. callipaeda. To the best of our knowledge, this is the first report of canine ocular thelaziosis caused by T. callipaeda from the Muntenia Region of Romania. PMID- 26898832 TI - Memantine Improves Attentional Processes in Fragile X-Associated Tremor/Ataxia Syndrome: Electrophysiological Evidence from a Randomized Controlled Trial. AB - Progressive cognitive deficits are common in patients with fragile X-associated tremor/ataxia syndrome (FXTAS), with no targeted treatment yet established. In this substudy of the first randomized controlled trial for FXTAS, we examined the effects of NMDA antagonist memantine on attention and working memory. Data were analyzed for patients (24 in each arm) who completed both the primary memantine trial and two EEG recordings (at baseline and follow-up) using an auditory "oddball" task. Results demonstrated significantly improved attention/working memory performance after one year only for the memantine group. The event-related potential P2 amplitude elicited by non-targets was significantly enhanced in the treated group, indicating memantine-associated improvement in attentional processes at the stimulus identification/discrimination level. P2 amplitude increase was positively correlated with improvement on the behavioral measure of attention/working memory during target detection. Analysis also revealed that memantine treatment normalized the P2 habituation effect at the follow-up visit. These findings indicate that memantine may benefit attentional processes that represent fundamental components of executive function/dysfunction, thought to comprise the core cognitive deficit in FXTAS. The results provide evidence of target engagement of memantine, as well as therapeutically relevant information that could further the development of specific cognitive or disease-modifying therapies for FXTAS. PMID- 26898835 TI - Enhancing the selectivity of kinase inhibitors in oncology: a chemical biology perspective. PMID- 26898834 TI - Relationships between host body condition and immunocompetence, not host sex, best predict parasite burden in a bat-helminth system. AB - Sex-biased parasitism highlights potentially divergent approaches to parasite resistance resulting in differing energetic trade-offs for males and females; however, trade-offs between immunity and self-maintenance could also depend on host body condition. We investigated these relationships in the big brown bat, Eptesicus fuscus, to determine if host sex or body condition better predicted parasite resistance, if testosterone levels predicted male parasite burdens, and if immune parameters could predict male testosterone levels. We found that male and female hosts had similar parasite burdens and female bats scored higher than males in only one immunological measure. Top models of helminth burden revealed interactions between body condition index and agglutination score as well as between agglutination score and host sex. Additionally, the strength of the relationships between sex, agglutination, and helminth burden is affected by body condition. Models of male parasite burden provided no support for testosterone predicting helminthiasis. Models that best predicted testosterone levels did not include parasite burden but instead consistently included month of capture and agglutination score. Thus, in our system, body condition was a more important predictor of immunity and worm burden than host sex. PMID- 26898836 TI - Full Valley and Spin Polarizations in Strained Graphene with Rashba Spin Orbit Coupling and Magnetic Barrier. AB - We propose a graphene-based full valley- and spin-polarization device based on strained graphene with Rashba spin orbit coupling and magnetic barrier. The underlying mechanism is the coexistence of the valley and single spin band gaps in a certain Fermi energy. By aligning the Fermi energy in the valley and single spin band gaps, remarkable valley- and spin-polarization currents can be accessed. PMID- 26898837 TI - Cryptochrome 1 in Retinal Cone Photoreceptors Suggests a Novel Functional Role in Mammals. AB - Cryptochromes are a ubiquitous group of blue-light absorbing flavoproteins that in the mammalian retina have an important role in the circadian clock. In birds, cryptochrome 1a (Cry1a), localized in the UV/violet-sensitive S1 cone photoreceptors, is proposed to be the retinal receptor molecule of the light dependent magnetic compass. The retinal localization of mammalian Cry1, homologue to avian Cry1a, is unknown, and it is open whether mammalian Cry1 is also involved in magnetic field sensing. To constrain the possible role of retinal Cry1, we immunohistochemically analysed 90 mammalian species across 48 families in 16 orders, using an antiserum against the Cry1 C-terminus that in birds labels only the photo-activated conformation. In the Carnivora families Canidae, Mustelidae and Ursidae, and in some Primates, Cry1 was consistently labeled in the outer segment of the shortwave-sensitive S1 cones. This finding would be compatible with a magnetoreceptive function of Cry1 in these taxa. In all other taxa, Cry1 was not detected by the antiserum that likely also in mammals labels the photo-activated conformation, although Western blots showed Cry1 in mouse retinal cell nuclei. We speculate that in the mouse and the other negative-tested mammals Cry1 is involved in circadian functions as a non-light-responsive protein. PMID- 26898838 TI - Clinical impact of breast MRI with regard to axillary reverse mapping in clinically node positive breast cancer patients following neo-adjuvant chemotherapy. AB - BACKGROUND: Axillary reverse mapping (ARM) is a technique that discerns axillary lymphatic drainage of the arm from the breast. In the current study, we retrospectively evaluated the incidence of metastatic axillary lymph node involvement, including ARM lymph nodes, in clinically node positive breast cancer patients (cN+ patients) in whom neo-adjuvant chemotherapy (NAC) was administered followed by primary ALND using breast MRI. PATIENTS AND METHODS: Data from 98 cN+ breast cancer patients were analysed retrospectively. Patients without residual axillary disease at breast MRI following NAC (RAD-, n = 64) were compared with patients with residual axillary disease (RAD+, n = 34). Presence of suspect axillary lymph nodes on pre-NAC and post-NAC breast MRI was determined by experienced breast radiologists and was correlated to histopathological findings. RESULTS: In the RAD-group residual axillary disease on pathological analysis following NAC was found in 25 patients (39.1%), as compared to 24 patients (70.6%) in the RAD + group (p = 0.003). Metastatic involvement of ARM lymph nodes following NAC was demonstrated in 5 patients (7.8%) in the RAD-group as compared to 10 patients (29.4%) in the RAD + group (p = 0.005). CONCLUSION: Breast MRI following NAC is not suitable to detect residual metastatic disease of the axilla. However, breast MRI post-NAC may be of use to identify cN+ patients with a low risk of ARM lymph node metastases. This may help to select a subgroup of cN+ patients in whom sparing of ARM lymph nodes during axillary lymph node dissection can be considered. PMID- 26898840 TI - Clinical utility of Axillary Reverse Mapping (ARM) in an era of changing perceptions concerning axillary surgery. PMID- 26898839 TI - Description and analysis of clinical pathways for oesophago-gastric adenocarcinoma, in 10 European countries (the EURECCA upper gastro intestinal group - European Registration of Cancer Care). AB - AIMS: Outcomes for patients with oesophago-gastric cancer are variable across Europe. The reasons for this variability are not clear. The aim of this study was to describe and analyse clinical pathways to understand differences in service provision for oesophageal and gastric cancer in the countries participating in the EURECCA Upper GI group. METHODS: A questionnaire was devised to assess clinical presentation, diagnosis, staging, treatment, pathology, follow-up and service frameworks across Europe for patients with oesophageal and gastric cancer. The questionnaire was issued to experts from 14 countries. The responses were analysed quantitatively and qualitatively and compared. RESULTS: The response rate was (10/14) 71.4%. The approach to diagnosis was similar. Most countries established a diagnosis within 3 weeks of presentation. However, there were different approaches to staging with variable use of endoscopic ultrasound reflecting availability. There has been centralisation of treatments in most countries for oesophageal surgery. The most consistent area was the approach to pathology. There were variations in access to specialist nurse and dietitian support. Although most countries have multidisciplinary teams, their composition and frequency of meetings varied. The two main areas of significant difference were research and audit and overall service provision. Observations on service framework indicated that limited resources restricted many of the services. CONCLUSION: The principle approaches to diagnosis, treatment and pathology were similar. Factors affecting the quality of patient experience were variable. This may reflect availability of resources. Standard pathways of care may enhance both the quality of treatment and patient experience. PMID- 26898841 TI - "Assessment of RIFLE and AKIN criteria to define acute renal dysfunction for HIPEC procedures for ovarian and non ovarian peritoneal malignances". AB - BACKGROUND: The acute renal dysfunction (ARD) is a common complication in cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). Our aim is evaluate the ARD post-HIPEC procedures using the RIFLE and AKIN criteria. Evaluate the risk factors and analyze ARD's impact on postoperative course. METHODS: From 2011 to 2014, in a retrospective way using a prospective database were operated by HIPEC procedure. The ARD was analyzed by RIFLE and AKIN criteria. The perioperative features were analyzed and a multivariate analysis was performed to define the risk factors to develop the ARD. RESULTS: 141 patients were treated and analyzed. The ARD was detected in 30.5% (Injury 18.4% and Failure 12.1%) when RIFLE criteria were applied. The multivariate analysis detected that decrease of pH during HIPEC [OR = 29.39 (5.09-169.76)], PCI [OR = 1.07 (1.01-1.15)] and ureteral catheters [OR = 12.71 (1.44-111.85)] were associated to the development of acute renal injury (ARI) post-HIPEC. Decrease of Na during HIPEC [OR = 1.15 (1.01-1.30)], intraoperative inotrope use [OR = 3.83 (1.12-13.09)] and PCI [OR = 1.06 (1.0-1.14)] were associated to acute renal failure (ARF) post-HIPEC. The ARD was related to a higher length of stay hospital (17.2 +/- 11 vs. 13.8 +/- 8 days) (p = 0.05) but no impact in early survival was observed in ARD group. CONCLUSIONS: The widespread use of RIFLE criteria for ARD would have major benefits in terms of accurately diagnosing patients undergone HIPEC procedures. The ARD has a detrimental impact in length of stay hospital. The knowledge of risk factors helps us to prevent the ARD post-HIPEC by means of an aggressive and multidisciplinary perioperative management. PMID- 26898842 TI - Technical considerations in performing posterior component separation with transverse abdominis muscle release. PMID- 26898843 TI - Morphogenetically active scaffold for osteochondral repair (polyphosphate/alginate/N,O-carboxymethyl chitosan). AB - Here we describe a novel bioinspired hydrogel material that can be hardened with calcium ions to yield a scaffold material with viscoelastic properties matching those of cartilage. This material consists of a negatively charged biopolymer triplet, composed of morphogenetically active natural inorganic polyphosphate (polyP), along with the likewise biocompatible natural polymers N,O-carboxymethyl chitosan (N,O-CMC) and alginate. The porosity of the hardened scaffold material obtained after calcium exposure can be adjusted by varying the pre-processing conditions. Various compression tests were applied to determine the local (nanoindentation) and bulk mechanical properties (tensile/compression test system for force measurements) of the N,O-CMC-polyP-alginate material. Determinations of the Young's modulus revealed that the stiffness of this comparably water rich (and mouldable) material increases during successive compression cycles to values measured for native cartilage. The material not only comprises viscoelastic properties suitable for a cartilage substitute material, but also displays morphogenetic activity. It upregulates the expression of genes encoding for collagen type II and aggrecan, the major proteoglycan within the articular cartilage, in human chondrocytes, and the expression of alkaline phosphatase in human bone-like SaOS-2 cells, as revealed in RT qPCR experiments. Further, we demonstrate that the new polyP-based material can be applied for manufacturing 3D solid models of cartilage bone such as of the tibial epiphyseal plate and the superior articular cartilage surface. Since the material is resorbable and enhances the activity of cells involved in regeneration of cartilage tissue, this material has the potential to be used for artificial articular cartilage implants. PMID- 26898844 TI - Harvests from bone marrow donors who weigh less than their recipients are associated with a significantly increased probability of a suboptimal harvest yield. AB - BACKGROUND: Previous studies have demonstrated the importance of bone marrow (BM) harvest yield in determining transplant outcomes, but little is known regarding donor and procedure variables associated with achievement of an optimal yield. We hypothesized that donor demographics and variables relating to the procedure were likely to impact the yield (total nucleated cells [TNCs]/kg recipient weight) and quality (TNCs/mL) of the harvest. STUDY DESIGN AND METHODS: To test our hypothesis, BM harvests of 110 consecutive unrelated donors were evaluated. The relationship between donor or procedure characteristics and the BM harvest yield was examined. RESULTS: The relationship between donor and recipient weight significantly influenced the harvest yield; only 14% of BM harvests from donors who weighed less than their recipient achieved a TNC count of more than 4 * 10(8) /kg compared to 56% of harvests from donors heavier than their recipient (p = 0.001). Higher-volume harvests were significantly less likely to achieve an optimal yield than lower-volume harvests (32% vs. 78%; p = 0.007), and higher volume harvests contained significantly fewer TNCs/mL, indicating peripheral blood contamination. BM harvest quality also varied significantly between collection centers adding to recent concerns regarding maintenance of BM harvest expertise within the transplant community. CONCLUSION: Since the relationship between donor and recipient weight has a critical influence yield, we recommend prioritizing this secondary donor characteristic when selecting from multiple well-matched donors. Given the declining number of requests for BM harvests, it is crucial that systems are developed to train operators and ensure expertise in this procedure is retained. PMID- 26898846 TI - Inorganic sulfur-nitrogen compounds: from gunpowder chemistry to the forefront of biological signaling. AB - The reactions between inorganic sulfur and nitrogen-bearing compounds to form S-N containing species have a long history and, besides assuming importance in industrial synthetic processes, are of relevance to microbial metabolism; waste water treatment; aquatic, soil and atmospheric chemistry; and combustion processes. The recent discovery that hydrogen sulfide and nitric oxide exert often similar, sometimes mutually dependent effects in a variety of biological systems, and that the chemical interaction of these two species leads to formation of S-N compounds brought this chemistry to the attention of physiologists, biochemists and physicians. We here provide a perspective about the potential role of S-N compounds in biological signaling and briefly review their chemical properties and bioactivities in the context of the chronology of their discovery. Studies of the biological role of NO revealed why its chemistry is ideally suited for the tasks Nature has chosen for it; realising how the distinctive properties of sulfur can enrich this bioactivity does much to revive 'die Freude am experimentellen Spiel' of the pioneers in this field. PMID- 26898847 TI - Service-wide management of healthy gestational weight gain following an implementation science approach. AB - The aim of health guidelines is to ensure consistency in the delivery of care to minimise health-related complications. However, even when good evidence is available, professionals do not necessarily implement it. Following a 2011 survey (Time 1) of staff in a tertiary maternity hospital, a number of service changes were implemented to facilitate best practice delivery of care to pregnant women regarding gestational weight gain (GWG). A (second) staff survey was then undertaken to re-assess staff knowledge, attitudes and behaviours around the management of GWG in our hospital. This cross-sectional, prospective online survey was distributed to staff in antenatal clinic. The survey assessed staff awareness of pregnancy-related weight complications, knowledge and application of specific guidelines, and a guideline adherence score was calculated. Sixty-nine staff (44.8% response rate) completed the 2014 (Time 2) survey. Just over half (51.9%) stated they were familiar with clinical guidelines regarding weight management in pregnancy. Guideline adherence ranged from 3.7 +/- 1.9 to 11.3 +/- 1.0 /15 across different professional groups; significant improvements with adherence by dietitians were noted over time. Despite minimal change over time in the overall adherence score, compliance with individual elements of the guideline recommendations comprising the adherence score differed. Improvements in staff practices and attitudes are apparent since the first survey. However, further improvements in guideline awareness and guideline elements are still required to improve the delivery of best practice antenatal GWG care. PMID- 26898848 TI - Post-stroke Fatigue is an Independent Predictor of Post-stroke Disability and Burden of Care: A Path analysis Study. AB - Post-stroke fatigue (PSF) is a common and one of the most distressing symptoms in stroke survivors. However, little is known about the relationship between severity of fatigue and the overall impact it has on post-stroke disability and burden of care. We aimed to examine the role of PSF in post-stroke disability and burden of care among stroke survivors after their first-ever stroke. METHODS: We prospectively recruited 163 subjects (35 females) from patients examined consecutively in a tertiary stroke care center in India, after their first-ever ischemic or hemorrhagic stroke (>3 months after event). In addition to demographic and clinical characteristics, the following assessments were done - SF-36 vitality domain (fatigue), Modified Rankin Scale (functional recovery), Hospital anxiety and depression scale (depression), Functional independence measure (disability and burden of care). We used path analysis to identify a model that will capture the interactions of fatigue, depression, and degree of functional recovery in stroke survivors. RESULTS: The severity of PSF positively correlated with the severity of disability and PSF had significant contribution to disability over and above functional recovery and depression, with all three factors accounting for 43% of the variance. Among the four models that were proposed to explore these relationships, the best fitting model showed that the effect of PSF is mediated through both the direct effect of fatigue on disability and through its interaction with depression, which remained a separate contributor to post-stroke disability and burden of care. CONCLUSIONS: PSF, therefore, is an important determinant of post-stroke disability and should be evaluated for successful post-stroke rehabilitation. PMID- 26898850 TI - Dye molecule bonded titanium alkoxide: a possible new type of dye for sensitized solar cells. AB - An organic dye coordinated titanium iso-propoxide compound is designed and synthesized. Taking advantage of the hydrolysis of the titanium alkoxide moiety on the surface of TiO2 electrode, the dye-semiconductor surface properties, including anchoring and dispersivity, are improved, which opens a new perspective to explore dyes for DSSCs. PMID- 26898849 TI - Development of a symmetric echo planar imaging framework for clinical translation of rapid dynamic hyperpolarized 13 C imaging. AB - PURPOSE: To develop symmetric echo planar imaging (EPI) and a reference scan framework for hyperpolarized 13 C metabolic imaging. METHODS: Symmetric, ramp sampled EPI with partial Fourier reconstruction was implemented on a 3T scanner. The framework for acquiring a reference scan on the 1 H channel and applied to 13 C data was described and validated in both phantoms and in vivo metabolism of [1 13 C]pyruvate. RESULTS: Ramp-sampled, symmetric EPI provided a substantial increase in the signal-to-noise ratio of the phantom experiments. The reference scan acquired on the 1 H channel yielded 13 C phantom images that varied in mean signal intensity <2%, compared with 13 C images reconstructed with a reference scan directly measured on the 13 C channel. The structural similarity index and dynamic time course from in vivo 13 C data further support the application of a 1 H reference scan to 13 C data to mitigate Nyquist ghost artifacts. CONCLUSION: Ramp-sampled, symmetric EPI with spectral-spatial excitation of a single metabolite provides a fast, robust, and clinically efficacious approach to acquire hyperpolarized 13 C dynamic molecular imaging data. The gains of this efficient sampling, combined with partial Fourier methods, enables large matrix sizes required for human studies. Magn Reson Med 77:826-832, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 26898851 TI - Antibiotic stewardship: prescribing social norms. PMID- 26898853 TI - INTERGROWTH-21st very preterm size at birth reference charts. PMID- 26898854 TI - HERMES: messenger for stroke interventional treatment. PMID- 26898852 TI - Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. AB - BACKGROUND: In 2015, five randomised trials showed efficacy of endovascular thrombectomy over standard medical care in patients with acute ischaemic stroke caused by occlusion of arteries of the proximal anterior circulation. In this meta-analysis we, the trial investigators, aimed to pool individual patient data from these trials to address remaining questions about whether the therapy is efficacious across the diverse populations included. METHODS: We formed the HERMES collaboration to pool patient-level data from five trials (MR CLEAN, ESCAPE, REVASCAT, SWIFT PRIME, and EXTEND IA) done between December, 2010, and December, 2014. In these trials, patients with acute ischaemic stroke caused by occlusion of the proximal anterior artery circulation were randomly assigned to receive either endovascular thrombectomy within 12 h of symptom onset or standard care (control), with a primary outcome of reduced disability on the modified Rankin Scale (mRS) at 90 days. By direct access to the study databases, we extracted individual patient data that we used to assess the primary outcome of reduced disability on mRS at 90 days in the pooled population and examine heterogeneity of this treatment effect across prespecified subgroups. To account for between-trial variance we used mixed-effects modelling with random effects for parameters of interest. We then used mixed-effects ordinal logistic regression models to calculate common odds ratios (cOR) for the primary outcome in the whole population (shift analysis) and in subgroups after adjustment for age, sex, baseline stroke severity (National Institutes of Health Stroke Scale score), site of occlusion (internal carotid artery vs M1 segment of middle cerebral artery vs M2 segment of middle cerebral artery), intravenous alteplase (yes vs no), baseline Alberta Stroke Program Early CT score, and time from stroke onset to randomisation. FINDINGS: We analysed individual data for 1287 patients (634 assigned to endovascular thrombectomy, 653 assigned to control). Endovascular thrombectomy led to significantly reduced disability at 90 days compared with control (adjusted cOR 2.49, 95% CI 1.76-3.53; p<0.0001). The number needed to treat with endovascular thrombectomy to reduce disability by at least one level on mRS for one patient was 2.6. Subgroup analysis of the primary endpoint showed no heterogeneity of treatment effect across prespecified subgroups for reduced disability (pinteraction=0.43). Effect sizes favouring endovascular thrombectomy over control were present in several strata of special interest, including in patients aged 80 years or older (cOR 3.68, 95% CI 1.95 6.92), those randomised more than 300 min after symptom onset (1.76, 1.05-2.97), and those not eligible for intravenous alteplase (2.43, 1.30-4.55). Mortality at 90 days and risk of parenchymal haematoma and symptomatic intracranial haemorrhage did not differ between populations. INTERPRETATION: Endovascular thrombectomy is of benefit to most patients with acute ischaemic stroke caused by occlusion of the proximal anterior circulation, irrespective of patient characteristics or geographical location. These findings will have global implications on structuring systems of care to provide timely treatment to patients with acute ischaemic stroke due to large vessel occlusion. FUNDING: Medtronic. PMID- 26898855 TI - CDC guidelines for pregnant women during the Zika virus outbreak. PMID- 26898857 TI - Orientation of polar molecules near charged protein interfaces. AB - We study the orientation of water and urea molecules and protein amide vibrations at aqueous alpha-lactalbumin and alpha-lactalbumin/urea interfaces using heterodyne-detected vibrational sum frequency generation. We vary the net charge of the protein by changing the pH. We find that the orientation of the water and urea molecules closely follows the net charge of the protein at the surface of the solution. In contrast, the net orientation of the amide groups of the backbone of the protein is independent of pH. We discuss the implications of these results for the mechanism by which urea denatures proteins. PMID- 26898858 TI - Interventions for Barrett's oesophagus and early cancer. PMID- 26898856 TI - Provision of social norm feedback to high prescribers of antibiotics in general practice: a pragmatic national randomised controlled trial. AB - BACKGROUND: Unnecessary antibiotic prescribing contributes to antimicrobial resistance. In this trial, we aimed to reduce unnecessary prescriptions of antibiotics by general practitioners (GPs) in England. METHODS: In this randomised, 2 * 2 factorial trial, publicly available databases were used to identify GP practices whose prescribing rate for antibiotics was in the top 20% for their National Health Service (NHS) Local Area Team. Eligible practices were randomly assigned (1:1) into two groups by computer-generated allocation sequence, stratified by NHS Local Area Team. Participants, but not investigators, were blinded to group assignment. On Sept 29, 2014, every GP in the feedback intervention group was sent a letter from England's Chief Medical Officer and a leaflet on antibiotics for use with patients. The letter stated that the practice was prescribing antibiotics at a higher rate than 80% of practices in its NHS Local Area Team. GPs in the control group received no communication. The sample was re-randomised into two groups, and in December, 2014, GP practices were either sent patient-focused information that promoted reduced use of antibiotics or received no communication. The primary outcome measure was the rate of antibiotic items dispensed per 1000 weighted population, controlling for past prescribing. Analysis was by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN32349954, and has been completed. FINDINGS: Between Sept 8 and Sept 26, 2014, we recruited and assigned 1581 GP practices to feedback intervention (n=791) or control (n=790) groups. Letters were sent to 3227 GPs in the intervention group. Between October, 2014, and March, 2015, the rate of antibiotic items dispensed per 1000 population was 126.98 (95% CI 125.68 128.27) in the feedback intervention group and 131.25 (130.33-132.16) in the control group, a difference of 4.27 (3.3%; incidence rate ratio [IRR] 0.967 [95% CI 0.957-0.977]; p<0.0001), representing an estimated 73,406 fewer antibiotic items dispensed. In December, 2014, GP practices were re-assigned to patient focused intervention (n=777) or control (n=804) groups. The patient-focused intervention did not significantly affect the primary outcome measure between December, 2014, and March, 2015 (antibiotic items dispensed per 1000 population: 135.00 [95% CI 133.77-136.22] in the patient-focused intervention group and 133.98 [133.06-134.90] in the control group; IRR for difference between groups 1.01, 95% CI 1.00-1.02; p=0.105). INTERPRETATION: Social norm feedback from a high-profile messenger can substantially reduce antibiotic prescribing at low cost and at national scale; this outcome makes it a worthwhile addition to antimicrobial stewardship programmes. FUNDING: Public Health England. PMID- 26898859 TI - Monolingual and bilingual children's social preferences for monolingual and bilingual speakers. AB - Past research has shown that young monolingual children exhibit language-based social biases: they prefer native language to foreign language speakers. The current research investigated how children's language preferences are influenced by their own bilingualism and by a speaker's bilingualism. Monolingual and bilingual 4- to 6-year-olds heard pairs of adults (a monolingual and a bilingual, or two monolinguals) and chose the person with whom they wanted to be friends. Whether they were from a largely monolingual or a largely bilingual community, monolingual children preferred monolingual to bilingual speakers, and native language to foreign language speakers. In contrast, bilingual children showed similar affiliation with monolingual and bilingual speakers, as well as for monolingual speakers using their dominant versus non-dominant language. Exploratory analyses showed that individual bilinguals displayed idiosyncratic patterns of preference. These results reveal that language-based preferences emerge from a complex interaction of factors, including preference for in-group members, avoidance of out-group members, and characteristics of the child as they relate to the status of the languages within the community. Moreover, these results have implications for bilingual children's social acceptance by their peers. PMID- 26898860 TI - [Clinical manifestations of 20 cases of the superior semicircular canal dehiscence syndrome and the intervention strategies]. AB - OBJECTIVE: The objective of this study is to investigate the clinical manifestations of the superior semicircular canal dehiscence syndrome(SSCDS) and the treatment strategies. METHODS: Data from 20 cases diagnosed with SSCDS from September 2004 to December 2014 were retrospectively analyzed in this study. The clinical presentations including symptoms, signs, audiological and vestibular function examination, and their imaging characteristics and treatment strategies were reviewed. RESULTS: All of the patients demonstrated variable degree of vertigo. Four patients could not tolerate the environmental noise. Autophony was noted in nine cases, among whom, two patients could feel their eye movements and heart beat, one patient could feel his footstep, one patient couldn't endure the singing by himself. Slow component vertical tortional eye movement away from the effected eye were observed in twelve patients when loud noise was given or middle ear or intracranial pressure increased. Head movement was induced by loud noise in one case. Ten patients presented with low frequency hearing loss. One case was concomitance with chronic otitis media and demonstrated severe sensorineural hearing loss. Nine patients demonstrated normal hearing. Decreased thresholds were showed by VEMP examination in six cases. Variable bone defect overlying in the SSCDS was confirmed by CT scans in all of the cases. The surgical repair of the superior semicircular canal dehiscence was performed through the middle cranial fossa approach in three cases and mastoid approach in two cases. The dizziness and the autophony were significantly alleviated after surgery. CONCLUSIONS: The clinical manifestations of SSCDS mainly demonstrate dizziness, autophony and loss of low frequency hearing. Treatment strategies are mainly composed of avoidance of environmental noise and shouting voice of the patients themselves. Surgical repair of the superior semicircular canal dehiscence was proposed to conduct, either through the middle cranial fossa approach or mastoid approach, when the patient couldn't tolerate the sypmtoms. PMID- 26898861 TI - [Analysis of quality of life and emotion symptoms in adolescents with allergic rhinitis in middle area of Jiangsu Province]. AB - OBJECTIVE: To evaluate the quality of life and emotion symptoms (anxiety symptom and depressive symptom) of adolescents with allergic rhinitis (AR) in middle area of Jiangsu province. METHODS: A case-control study on quality of life and emotion symptoms among 220 AR adolescents and 240 controls was performed. The participants were investigated by questionnaires of RQLQ, ICD, and SCARED.SPSS 13.0 software was used to analyze the data. RESULTS: The scores of RQLQ five dimensions with AR were higher than the controlled subjects respectively(all P<0.01). The score of SCARED((24.15+/-4.89) vs (19.13+/-3.17)) but not ICD((20.78+/-4.4) vs (19.97+/-3.45)) in AR was higher than the controlled subjects(t=12.79, P<0.05; t=2.34, P>0.05). Furthermore, anxiety symptom was significantly associated with nasal symptoms, other problems and behavior problems. CONCLUSIONS: The quality of life and emotion symptoms were significantly affected by AR. It is important to pay attention to overall health in AR adolescents. PMID- 26898862 TI - [Analysis of the curative effect of intralesional steroid injection combined with acid-suppressive therapy for laryngeal contact granuloma]. AB - OBJECTIVE: To study the efficacy of intralesional steroid injection combined with acid-suppressive therapy for laryngeal contact granuloma. METHODS: Eighty eight patients with laryngeal contact granuloma diagnosed from March 2010 to October 2014 were reviewed.Twenty-one patients took intralesional steroid injection combined with acid-suppressive therapy as experimental group (4 patients in initial treatment group, 17 patients in non-initial treatment group), other 67 patients only received acid-suppressive therapy as control group. The clinical data of these patients was analyzed. RESULTS: In experimental group, 15 patients were cured (71.43%) and the average cure time were (3.80+/-0.43) months, total injection time was 2-6 times and the median was 3 times. In control group, 50 patients were cured (74.63%) and the average cure time were (5.31+/-0.38) months. No any systemic and local complications were found in all the patients during the follow-up period of 6-42 months. The cure rate had no significant difference between the experimental group and control group, but the cure time in the former group was shorter than that in the latter group (Z=-2.093, P=0.036). In the experimental group, the initial treatment patients had no significant difference in cure rate and cure time compared with non initial patients (chi(2)=1.112, P=0.544; Z=0.000, P=1.000). CONCLUSION: Intralesional steroid injection combined with acid-suppressive therapy can be recommended as a safe and effective alternative therapy for laryngeal contact granuloma, especially the refractory granuloma. PMID- 26898863 TI - [Segmental tracheal resection and anastomosis for the treatment of cicatricial stenosis in cervical tracheal]. AB - OBJECTIVE: To evaluate the efficacy of segmental tracheal resection with end-to end anastomosis for cicatricial cervical tracheal stenosis. METHODS: The clinical outcomes of 40 patients treated with tracheal resection were retrospectively reviewed. There were 28 male patients and 12 female patients with the age ranged from 6 to 64 years (mean 33.7 years). The degree of stenosis was classified according to Myer-Cotton classification as follows: grade II (n=7), grade III (n=22) and grade IV (n=11). The stenosis extension ranged from 1.0 to 4.3 cm (mean 2.5 cm). The causes of the stenosis were postintubation (n=33), cervical trauma (n=6) and resection of tracheal neoplasm (n=1). RESULTS: Thirty four(85.0%) patients were decannulated and 6 failed. Of the 6 patients failed, 4 were decannulated after reoperation with the sternohyoid myocutaneous flap or thyroid alar cartilage graft. Complications occurred in 10 patients. In 8 patients granulation tissues formed at the site of the tracheal anastomosis, which needed endoscopic resction, and in 2 patients anastomosic dehiscence occurred. No injury to recurrent laryngeal nerve or trachoesophageal fistula occurred. CONCLUSION: Segmental tracheal resection with end-to-end anastomosis is an effective surgical method for tracheal stenosis, which has a higher successful rate for primary operation and shorter therapeutic period. PMID- 26898864 TI - [Study on the pharyngeal constriction and function of cricopharyngeal muscle in normal persons using dynamic magnetic resonance imaging]. AB - OBJECTIVE: To investigate the superiority of dynamic magnetic resonance imaging as an assessment method of pharyngeal constriction and cricopharyngeal muscle function, and introduce a new way to measure the pharyngeal constriction ratio, anteroposterior diameter of esophageal entrance and thickness of cricopharyngeal muscle in healthy volunteers. METHODS: Twenty volunteers who were assessed as normal by fiberoptic endoscopic evaluation of swallowing and videofluoroscopic swallowing study were included in this study. With the use of 3.0T magnetic resonance imaging, Fiesta sequence and Asset technique, the median sagittal plane and intervertebral transverse plane from C1 to C5 were scanned repeatedly. Pharyngeal constriction ratio in the median sagittal and intervertebral transverse plane, anteroposterior diameter of esophageal entrance and thickness of cricopharyngeal muscle were assessed and the data were analysed by SPSS13.0. RESULTS: The intervertebral transverse plane between C1 and C2 was superior in observation of pharyngeal constriction ratio in the same way that the plane between C4 and C5 was superior in cricopharyngeal evaluation. The average of sagittal and intervertebral pharyngeal constriction ratio were estimated as 0.08+/-0.02, 0.09+/-0.04 respectively and the average of thickness of cricopharyngeal muscle and anteroposterior diameter of esophageal entrance were (6.50+/-1.69) mm, (1.99+/-0.76) mm respectively. CONCLUSION: Dynamic magnetic resonance imaging was superior in assessing the function of pharyngeal constriction and cricopharyngeal muscle by scanning the swallowing process in the median sagittal and intervertebral transverse plane. PMID- 26898865 TI - [Role of Narrow-band imaging endoscopy in the diagnosis of hypopharyngeal carcinoma]. PMID- 26898866 TI - [The characteristic of metabolics of female papillary thyroid carcinoma and its relationship with primary tumor size and cervical lymph node metastases]. AB - OBJECTIVE: To analyze the metabolic profiles of the female papillary thyroid carcinoma (PTC) and the relationship between the metabolic profiles and primary tumor size and cervical lymph node metastasis using a metabolomics approach. METHODS: Forty-three cases of female PTC were enrolled in this study. Gas chromatography-time-of-flight mass spectrometry and ultra performance liquid chromatography-time of flight-mass spectrometry were employed for analyzing metabolic profiles of tumor tissues and adjacent normal tissues in the female PTC. Cases were divided into Group T1 (tumor size<=2.0 cm) and Group T2 (tumor size>2.0 cm) according to the tumor size, and divided into Group N- (with negative cervical lymph node) and Group N+ (with positive cervical lymph node) according to the cervical lymph node conditions. We compared the metabolomic profiles between these groups. RESULTS: A panel of 46 differentially expressed metabolites was identified in the PTC specimens, compared with normal tissues. Increased metabolism of amino acid, purine and pyrimidine, tryptophan acid, one carbon, glycolysis, taurine and hypotaurine, and fatty acid were found in PTC tumors tissues. Amino acids, purine and pyridine, tryptophan, and carbon metabolism increased significantly in the tumor tissues of Group T2 compared with Group T1, while glycolysis, amino acid, purine and pyridine, tryptophan, and carbon metabolism increased significantly in the specimens of Group N+ . CONCLUSION: Distinct metabolic profiles were identified in the female PTC tissues, which were related to the primary tumor size and cervical lymph node metastases. PMID- 26898867 TI - [Clinical significance of the preoperative neutrophil lymphocyte ratio in the evaluation of the prognosis of laryngeal carcinoma]. AB - OBJECTIVE: To explore the effect of preoperative neutrophil lymphocyte ratio (NLR) on the prognosis of patients with laryngeal carcinoma. METHODS: Clinical data of 202 patients with laryngeal carcinoma treated from January 2004 to October 2009 were retrospective analyzed to determine the optimal critical value of NLR. To study whether NLR is an independent factor affecting the recurrence and 5-year survival rate of patients with laryngeal cancer after surgery, single factor and multivariate analyses were performed. The factors included age, gender, T stage, pathological differentiation, lymph node metastasis, primary tumor site and NLR value. The relationship between NLR and cervical lymph node metastasis was analyzed. RESULTS: The optimal critical value of NLR was 2.85, by which cases were divided into high NLR group (NLR>=2.85) and low NLR group (NLR<2.85). Single factor and multivariate analyses indicated that T staging, lymph node metastasis, primary tumor location, and NLR were the independent factors affecting the recurrence of laryngeal carcinoma. T stage and lymph node metastasis were the independent factors affecting 5-year survival rate of laryngeal carcinoma. The increase of NLR value increased the rate of cervical lymph node metastasis. CONCLUSION: Preoperative NLR level influences the recurrence and cervical lymph node metastasis of laryngeal carcinoma and can be considered a prognosis factor of laryngeal cancer. PMID- 26898868 TI - [Scalp surface skin grafts in reconstruction of external auditory meatus in congenital aural atresia]. AB - OBJECTIVE: To investigate the clinical application of scalp skin grafts in reconstruction of external auditory meatus in congenital aural atresia. METHODS: We conducted a retrospective study on 85 patients of congenital aural atresia, all of whom were unilateral, operated from March of 2008 to December of 2010 in ENT department of the Sun Yat-Sen Memorial Hospital. The patients enrolled in the study were between 6 to 37 years old (median age 12 years), 55 male and 30 female. Scalp surface graft in ipsilateral temporal region was harvested to cover the bony external auditory meatus. RESULTS: All of these scalp split-thickness skin grafts survived without necrosis, no restenosis was found in these external auditory meatus. Neither scar nor alopecia was found in the skin-harvesting region, and hairs grew well. Granulations occurred in 27 cases in the first to sixth month posteroperatively, 20 cases recovered after local treatment. In the first year, 30 cases obtained hearing improvement more than 15 dB, 36 cases gained more than 25 dB and 19 cases gained more than 35 dB. Totally 8 patients were lost in the 4 to 5 years of follow-up, 70 cases (70/77, 90.9%) developed new external auditory meatus, 7 cases (7/77, 9.1%) suffered from stenosis in different degrees, but no atresia was found in these patients. CONCLUSION: Scalp split-thickness skin grafts has significant clinical advantage in meatoplasty of congenital aural atresia. PMID- 26898869 TI - [Resection of the recurrent third branchial fistula under gastroscope with assistance of yellow zebra guidewire]. AB - OBJECTIVE: To investigate clinical aspects and a new operative method for resecting third branchial fistula. METHODS: The clinical aspects of 4 patients with third branchial fistula were retrospectively analyzed. It is difficult to locate the inner orifice of fistula through neck path due to tiny diameter of inner orifice. The inner orifice could be found and closed effectively by inserting yellow zebra guidewire from sinus piriformis with gastroscope. The mucous membrane of sinus piriformis could not be damaged due to the soft pointed end of yellow zebra guidewire. RESULTS: 4 cases were treated successfully without pharyngeal fistula or recurrent laryngeal nerve injury. No recurrent infections were found in all cases with follows-up of 6-66 months. CONCLUSION: Ineffectiveness of radiography with meglumine diatrizoate or oral administration of methylene blue before operation indicates tiny fistula. In this case, resection of third branchial fistula with the assistance of gastroscope and yellow zebra guidewire under general anesthesia can be performed. This innovative method of diagnosis and treatment is worth of application clinically. PMID- 26898870 TI - [Experimental study of metabonomics in the diagnosis of allergic rhinitis in mice]. AB - OBJECTIVE: To investigate the application of metabonomics in the diagnosis of allergic rhinitis. METHODS: Eighty male Kunming mice were randomly divided into two groups, control group (30 mice) and allergic rhinitis (AR) group (50 mice). After modeling, removal behavior score more than 6 and retain 30 mice behavior score equal to 6.Collect the mice peripheral blood and preparate blood serum, using UPLC-MS chromatographic separation and detection. The data were pretreated by SPSS and Excel, after chromatographic peak matching by MZmine. Firstly , delete interference data in accordance with the 80% rule .Then, the investigate data were analyzed by PLS-DA and PCA-X. RESULTS: Three-dimensional view of the control group (30 mice) and AR group (30 mice) blood serum data was drawn using PCA-X and PLS-DA method. The two groups of samples could be completely separated through views, which showed that there was a significant difference between the two groups of data. There were some differences in the blood metabolites between the control group and AR group . CONCLUSION: The study showed that it was scientific and feasible to diagnose AR using the metabonomics. PMID- 26898871 TI - [Thoracic duct ligation under thoracoscope to deal with severe neck chyle leakage after neck dissection]. PMID- 26898872 TI - [Misdiagnosis of subglottic foreign body in a case of acute laryngitis]. PMID- 26898873 TI - [A foreign body migrating from pharynx into neck in one case]. PMID- 26898874 TI - [Temporal bone teratoma: a case report]. PMID- 26898875 TI - [Nasal polyposis in Peutz-Jeghers syndrome: a case report]. PMID- 26898876 TI - [Synovial sarcoma of the nasal cavity: a case report]. PMID- 26898877 TI - [A patient with serious sinusal malformation]. PMID- 26898878 TI - [Pharyngeal foreign body sensation and slurred speech as starting symptoms of internal carotid artery malformation: a case report]. PMID- 26898879 TI - [Exploration on the new diagnostic criteria and related issues of Meniere's disease]. PMID- 26898880 TI - [Epidemiology and management guidelines of thyroid cancer]. PMID- 26898881 TI - [New therapeutic strategies in allergic rhinitis]. AB - Allergic rhinitis (AR) is a nasal inflammatory, IgE-mediated disease that occurs when some individuals inhales something he or she is allergic to, such as pollen or animal dander. It is also a refractory disease with high prevalence in the field of rhinology. The treatment of AR is really a difficult and challenging task because of the high prevalence, economic burden and the interference to the quality of life. At present, nasal corticosteroid and antihistamines were the mainly therapies, however, there is up to 40% patients not satisfactory to these therapies. So exploring new therapy or target is necessary. This article will review the results of previous studies focused on the new therapies of AR. PMID- 26898882 TI - [The role definition of lateral arm free flap in reconstruction after head and neck cancer surgery]. AB - Application of free flap is one of the important repair means in head and neck surgery. A variety of free flaps, such as anterolateral thigh flap, have showed unique advantages in repair for tissue defects after resection of head and neck tumor, and have became increasing popularity. Lateral arm flee flap is an important repair means in plastic surgery, which has developed more than 30 years, but the application of this flap for reconstruction in head and neck surgery is relatively backward, with few reports. This review focuses on the creativity and innovation, the relationship between anatomy and clinical application, and the application status and prospects for lateral arm flee flap in individual head and neck reconstruction surgery. PMID- 26898883 TI - Ionic self-assembly affords mesoporous ionic networks by crosslinking linear polyviologens with polyoxometalate clusters. AB - Ionic-bonded mesoporous ionic networks were prepared by the ionic self-assembly of polyoxometalate (POM) clusters with linear cationic polyviologens in water. The POM-enriched PMIN-2(V) possesses a high surface area up to 120 m(2) g(-1), exhibiting superior non-noble metal heterogeneous catalytic performance in the ambient aerobic selective oxidation of 5-hydroxymethylfurfural. PMID- 26898885 TI - Corrigendum: Energy dissipation and error probability in fault-tolerant binary switching. PMID- 26898886 TI - Interstitial lung disease in the intensive unit care setting. PMID- 26898884 TI - MSI2 is required for maintaining activated myelodysplastic syndrome stem cells. AB - Myelodysplastic syndromes (MDS) are driven by complex genetic and epigenetic alterations. The MSI2 RNA-binding protein has been demonstrated to have a role in acute myeloid leukaemia and stem cell function, but its role in MDS is unknown. Here, we demonstrate that elevated MSI2 expression correlates with poor survival in MDS. Conditional deletion of Msi2 in a mouse model of MDS results in a rapid loss of MDS haematopoietic stem and progenitor cells (HSPCs) and reverses the clinical features of MDS. Inversely, inducible overexpression of MSI2 drives myeloid disease progression. The MDS HSPCs remain dependent on MSI2 expression after disease initiation. Furthermore, MSI2 expression expands and maintains a more activated (G1) MDS HSPC. Gene expression profiling of HSPCs from the MSI2 MDS mice identifies a signature that correlates with poor survival in MDS patients. Overall, we identify a role for MSI2 in MDS representing a therapeutic target in this disease. PMID- 26898887 TI - Lymphomatoid granulomatosis - A rare pulmonary lymphoproliferative disease. PMID- 26898888 TI - Cystic fibrosis - characterization of the adult population in Portugal. AB - INTRODUCTION: The incidence of cystic fibrosis (CF) in Portugal is estimated at 1:8000 live births, although there is a lack of accurate statistics. The average life expectancy has been steadily increasing and CF is no longer an exclusively pediatric disease. OBJECTIVES: Characterize the Portuguese adult population with the diagnosis of CF. METHODS: Retrospective study based on clinical data of adult CF follow-up patients in the three specialized centers in Portugal where all of CF patients are seen, during 2012. RESULTS: In 2012, there were 89 follow-up patients, 48 (54%) female and 15 (17%) lung transplanted. The average age was 31.3+/-9 years. The median age at diagnosis was 13 years and 34 (38%) were diagnosed in adulthood. The most frequent mutation was F508del (54.9%). Of the 89 patients, 49 patients (56%) had pancreatic insufficiency, 7 (9%) were diabetic and 42 patients (47.7%) had a body mass index (BMI) <20kg/m(2). As to ventilatory function, the average value of the forced expiratory volume in 1s (FEV1) was 58.45+/-28.59%. Only one of 77 patients did not have chronic airway infection. The most commonly isolated germ was methicillin-sensitive Staphylococcus aureus in 49 patients (55%). During 2012, two patients (2.2%) died at the ages of 21 and 36 years. DISCUSSION: This study is the first description of the Portuguese adult CF population, which is particularly important since it can give us a better understanding of the real situation. A significant percentage of these patients were diagnosed in adulthood, which highlights the need for diagnostic suspicion in a patient with chronic lung disease and atypical manifestations. PMID- 26898889 TI - Evaluation of adverse health risks associated with antineoplastic drug exposure in nurses at two Chinese hospitals: The effects of implementing a pharmacy intravenous admixture service. AB - OBJECTIVE: To determine the health risks of antineoplastic drugs (ADs) occupational exposure in nurses and to evaluate the effects of implementing a pharmacy intravenous admixture service (PIVAS) in two Chinese hospitals. METHODS: The laboratory findings were collected from annual staff physical examination data. Reproductive toxicity and clinical manifestations were self-reported via a questionnaire. RESULTS: Hematotoxicity, organ damage, reproductive toxicity, and clinical manifestations associated with AD exposure were markedly higher in oncology nurses than unexposed nurses. Application of PIVAS led to a significant restoration of the blood cell counts and kidney function, and a reduction in adverse reproductive outcomes among oncology nurses. Pronounced symptoms related to AD exposure were alleviated as well. CONCLUSION: Oncology nurses who work with AD's experienced more adverse health outcomes than unexposed nurses. The health risks to AD were significantly alleviated by implementing a pharmacy intravenous admixture service. PMID- 26898891 TI - New and old techniques in cell and developmental biology. PMID- 26898890 TI - Prioritizing Variants in Complete Hereditary Breast and Ovarian Cancer Genes in Patients Lacking Known BRCA Mutations. AB - BRCA1 and BRCA2 testing for hereditary breast and ovarian cancer (HBOC) does not identify all pathogenic variants. Sequencing of 20 complete genes in HBOC patients with uninformative test results (N = 287), including noncoding and flanking sequences of ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, EPCAM, MLH1, MRE11A, MSH2, MSH6, MUTYH, NBN, PALB2, PMS2, PTEN, RAD51B, STK11, TP53, and XRCC2, identified 38,372 unique variants. We apply information theory (IT) to predict and prioritize noncoding variants of uncertain significance in regulatory, coding, and intronic regions based on changes in binding sites in these genes. Besides mRNA splicing, IT provides a common framework to evaluate potential affinity changes in transcription factor (TFBSs), splicing regulatory (SRBSs), and RNA-binding protein (RBBSs) binding sites following mutation. We prioritized variants affecting the strengths of 10 splice sites (four natural, six cryptic), 148 SRBS, 36 TFBS, and 31 RBBS. Three variants were also prioritized based on their predicted effects on mRNA secondary (2 degrees ) structure and 17 for pseudoexon activation. Additionally, four frameshift, two in-frame deletions, and five stop-gain mutations were identified. When combined with pedigree information, complete gene sequence analysis can focus attention on a limited set of variants in a wide spectrum of functional mutation types for downstream functional and co-segregation analysis. PMID- 26898892 TI - Direct Optical Probing of Transverse Electric Mode in Graphene. AB - Unique electrodynamic response of graphene implies a manifestation of an unusual propagating and localised transverse-electric (TE) mode near the spectral onset of interband transitions. However, excitation and further detection of the TE mode supported by graphene is considered to be a challenge for it is extremely sensitive to excitation environment and phase matching condition adherence. Here for the first time, we experimentally prove an existence of the TE mode by its direct optical probing, demonstrating significant coupling to an incident wave in electrically doped multilayer graphene sheet at room temperature. We believe that proposed technique of careful phase matching and obtained access to graphene's TE excitation would stimulate further studies of this unique phenomenon, and enable its potential employing in various fields of photonics as well as for characterization of graphene. PMID- 26898893 TI - The Unintended Consequences of an FDA Warning: The Case of Power Morcellation in Myoma Surgery. AB - OBJECTIVE: To study patients' perspectives regarding the risks and benefits of the use of power morcellation. DESIGN: Cross-sectional survey (Canadian Task Force classification II-3). SETTING: Academic tertiary referral hospital. PATIENTS: Women waiting in gynecology waiting rooms. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: Of the 321 women invited, 310 (97%) responded to the survey; 19% of the participants had myomas requiring treatment, and the other 81% did not. Women with myomas were more likely to be aware of the risks of morcellation (32% vs 14%; p < .001); 29% obtained their information directly from their physicians, while 71% obtained it from other resources. After reading about the risks and benefits of open and MIS approaches to myoma removal, 65% would choose an MIS approach if the risk of cancer spread was up to 0.3% (1 in 350). The majority of women (75%) felt that the government should not have a role in surgical decision making, but should provide information to help patients make decisions. CONCLUSION: Women have different risk tolerances. Most women would be willing to take the 1 in 350 (0.3%) risk of undiagnosed sarcoma spread to benefit from MIS approaches. FDA warnings may have unintended consequences by limiting the acceptable medical choices available for patients. PMID- 26898894 TI - Robotic Transperitoneal Infrarenal Para-Aortic Lymphadenectomy With Double Docking: Technique, Learning Curve, and Perioperative Outcomes. AB - Para-aortic lymphadenectomy (PAL) is a challenging procedure performed by minimally invasive surgery in very few centers, owing to its intrinsic technical complexity. We describe and assess the feasibility and learning curve of robotic double-docking transperitoneal infrarenal PAL combined with oncological pelvic surgery. Fifty patients who underwent this procedure using the Da Vinci S surgical system between March 2010 and May 2013 were included. The mean operating time for PAL surgery was 76 minutes (range, 32-150 minutes), and the mean number of lymph nodes per patient was 11.8 (range, 1-44). There were no conversions to laparotomy or laparoscopy. The mean length of hospital stay was 2 days (range, 1 25 days). Statistically significant decreases were noted for mean table rotation time (17 +/- 6.8 minutes vs 13 +/- 3.6 minutes; p = .02) and mean PAL operating time (85.4 +/- 25.8 minutes vs 69.8 +/- 24.6 minutes; p = .04) when comparing the first 20 patients and the last 30 patients. The number of nodes was similar in the first 20 patients and last 30 patients. The double-docking transperitoneal infrarenal PAL technique combined with oncological pelvic surgery is feasible, with minimal morbidity and a short learning curve. PMID- 26898896 TI - Pillars for Surgical Treatment of Bowel Endometriosis. PMID- 26898895 TI - Single-site Versus Multiport Robotic Hysterectomy in Benign Gynecologic Diseases: A Retrospective Evaluation of Surgical Outcomes and Cost Analysis. AB - OBJECTIVE: To compare the surgical outcomes and costs of robotic-assisted hysterectomy with the single-site (RSSH) or multiport approach (RH). DESIGN: A retrospective analysis of a prospectively collected database (Canadian Task Force classification II1). SETTING: A university hospital. PATIENTS: Consecutive women who underwent robotic-assisted total laparoscopic hysterectomy and bilateral salpingo-oophorectomy for the treatment of benign gynecologic diseases. INTERVENTIONS: Data on surgical approach, surgical outcomes, and costs were collected in a prospective database and retrospectively analyzed. MEASUREMENTS AND MAIN RESULTS: The total operative time, console time, docking time, estimated blood loss, conversion rate, and surgical complications rate were compared between the 2 study groups. Cost analysis was performed. One hundred four patients underwent total robotic-assisted hysterectomy and bilateral salpingo oophorectomy (45 RSSH and 59 RH). There was no significant difference in the indications for surgery and in the characteristics of the patients between the 2 study groups. There was no significant difference between the single-site and multiport approach in console time, surgical complication rate, conversion rate, and postoperative pain. The docking time was lower in the RH group (p = .0001). The estimated blood loss and length of hospitalization were lower in the RSSH group (p = .0008 and p = .009, respectively). The cost analysis showed significant differences in favor of RSSH. CONCLUSION: RSSH should be preferred to RH when hysterectomy is performed for benign disease because it could be at least as equally effective and safe with a potential cost reduction. However, because of the high cost and absence of clear advantages, the robotic approach should be considered only for selected patients. PMID- 26898897 TI - Relationship between lower limbs kinematic variables and effectiveness of sprint during maximum velocity phase. AB - PURPOSE: The aim of the study was to determine the relationships between time of running over a 15-25 m section of a 30-meter run along a straight line and changes in the angle and angular velocity observed in ankle, knee and hip joints. Therefore, the authors attempted to answer the question of whether a technique of lower limbs movement during the phase of sprint maximum velocity significantly correlates with the time of running over this section. METHODS: A group of 14 young people from the Lower Silesia Voivodeship Team participated in the experiment. A Fusion Smart Speed System was employed for running time measurements. The kinematic data were recorded using Noraxon MyoMotion system. RESULTS: There were observed statistically significant relationships between sprint time over a section from 15 to 25 m and left hip rotation (positive) and between this time and left and right ankle joint dorsi-plantar flexion (negative). CONCLUSIONS: During the maximum velocity phase of a 30 m sprint, the effect of dorsi-plantar flexion performed in the whole range of motion was found to be beneficial. This can be attributed to the use of elastic energy released in the stride cycle. Further, hip rotation should be minimized, which makes the stride aligned more along a line of running (a straight line) instead of from side to side. PMID- 26898898 TI - Diacylglycerol levels modulate the cellular distribution of the nicotinic acetylcholine receptor. AB - Diacylglycerol (DAG), a second messenger involved in different cell signaling cascades, activates protein kinase C (PKC) and D (PKD), among other kinases. The present work analyzes the effects resulting from the alteration of DAG levels on neuronal and muscle nicotinic acetylcholine receptor (AChR) distribution. We employ CHO-K1/A5 cells, expressing adult muscle-type AChR in a stable manner, and hippocampal neurons, which endogenously express various subtypes of neuronal AChR. CHO-K1/A5 cells treated with dioctanoylglycerol (DOG) for different periods showed augmented AChR cell surface levels at short incubation times (30min-4h) whereas at longer times (18h) the AChR was shifted to intracellular compartments. Similarly, in cultured hippocampal neurons surface AChR levels increased as a result of DOG incubation for 4h. Inhibition of endogenous DAG catabolism produced changes in AChR distribution similar to those induced by DOG treatment. Specific enzyme inhibitors and Western blot assays revealed that DAGs exert their effect on AChR distribution through the modulation of the activity of classical PKC (cPKC), novel PKC (nPKC) and PKD activity. PMID- 26898899 TI - A Curious Case of Continuous Incontinence. AB - Obstructed hemivagina, ipsilateral renal anomaly (OHVIRA) is a rare Mullerian duct abnormality with renal manifestations. Classical presentation is an adolescent female with abdominal pain following menarche. Because of its rarity, diagnosis is often delayed. There have been <20 reported cases of prepubertal OHVIRA. We present a case of missed OHVIRA diagnosis that presented with continuous incontinence following incision of the obstructed hemivagina and discuss the current medical literature on this subject. PMID- 26898900 TI - Contemporary Review of Treatment Options for Peyronie's Disease. AB - Peyronie's disease (PD) is a penile wound-healing disorder resulting in fibrotic plaque in the tunica albuginea, likely resulting from micro trauma. Due to variable disease presentations, a myriad of proposed treatment options, physician misconceptions about the disorder, and severe psychological distress in afflicted patients, PD can be a difficult to manage entity. This review seeks to provide a current and comprehensive overview of oral, topical, intralesional, mechanical, and surgical therapies for PD. PMID- 26898901 TI - Scanning Electron Microscopy Reveals Two Distinct Classes of Erythroblastic Island Isolated from Adult Mammalian Bone Marrow. AB - Erythroblastic islands are multicellular clusters in which a central macrophage supports the development and maturation of red blood cell (erythroid) progenitors. These clusters play crucial roles in the pathogenesis observed in animal models of hematological disorders. The precise structure and function of erythroblastic islands is poorly understood. Here, we have combined scanning electron microscopy and immuno-gold labeling of surface proteins to develop a better understanding of the ultrastructure of these multicellular clusters. The erythroid-specific surface antigen Ter-119 and the transferrin receptor CD71 exhibited distinct patterns of protein sorting during erythroid cell maturation as detected by immuno-gold labeling. During electron microscopy analysis we observed two distinct classes of erythroblastic islands. The islands varied in size and morphology, and the number and type of erythroid cells interacting with the central macrophage. Assessment of femoral marrow isolated from a cavid rodent species (guinea pig, Cavis porcellus) and a marsupial carnivore species (fat tailed dunnarts, Sminthopsis crassicaudata) showed that while the morphology of the central macrophage varied, two different types of erythroblastic islands were consistently identifiable. Our findings suggest that these two classes of erythroblastic islands are conserved in mammalian evolution and may play distinct roles in red blood cell production. PMID- 26898902 TI - A novel HLA-DRB1 allele, HLA-DRB1*12:48. AB - HLA-DRB1*12:48 differs from DRB1*12:09, by a single synonymous nucleotide at position 266. PMID- 26898905 TI - Resistance to ethanol sensitization is associated with a loss of synaptic plasticity in the hippocampus. AB - Behavioral sensitization to repeated ethanol (EtOH) exposure induces an increase in locomotor activity in mice. However, not all animals express such sensitization. Although the literature indicated that the hippocampus may play a role in EtOH sensitization, it is not known whether behavioral sensitization to EtOH is associated with preferential changes in bidirectional synaptic plasticity, i.e., LTP and LTD, two markers of learning capabilities that have also been shown to be involved in addictive behavior. In the present study, we examined whether the vulnerability to develop and express behavioral sensitization to EtOH is associated with altered bidirectional synaptic plasticity in the CA1 area of the dorsal hippocampus. For this purpose, we analyzed both LTP and LTD in resistant and sensitized mice during the expression phase, i.e., 7 days after 10 days of repeated EtOH i.p. administration. We found that resistant mice showed a lack of LTD without changes in LTP. The lack of LTD was associated with an increase in GluN2A protein level and was not due to an altered level of neuronal activity, since no difference was observed between the number of c-FOS positive neurons in sensitized and resistant mice. Given that both types of synaptic plasticity signals may have distinct roles in specific learning and behaviors, our results suggest that resistant mice could exhibit different phenotypes in terms of learning/memory and addictive behaviors compared to sensitized ones. Synapse 71:e21899, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 26898906 TI - The safety of ezetimibe and simvastatin combination for the treatment of hypercholesterolemia. AB - INTRODUCTION: In the light of the most recent and stricter dyslipidemia treatment guidelines, the need for combination hypolipidemic therapy is increasing. Ezetimibe plus simvastatin is available as a fixed dose therapy offering an efficient hypolipidemic treatment choice. Based on the positive results of the IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) trial, the use of this drug combination is expected to increase in the next years. AREAS COVERED: This review discusses the current evidence regarding the safety of ezetimibe/simvastatin combination. Current evidence regarding possible associated side effects (musculoskeletal, gastrointestinal, endocrine, hematological, renal, ophthalmologic, allergic, malignancy) and drug interactions of this combination is thoroughly discussed. EXPERT OPINION: Ezetimibe and simvastatin treatment, either as a single pill or the combined use of the individual compounds, offers limited additional risk compared with simvastatin monotherapy and comprises a safe and efficient choice for dyslipidemia treatment in high-risk and diabetic patients. PMID- 26898903 TI - Probing of miniPEGgamma-PNA-DNA Hybrid Duplex Stability with AFM Force Spectroscopy. AB - Peptide nucleic acids (PNA) are synthetic polymers, the neutral peptide backbone of which provides elevated stability to PNA-PNA and PNA-DNA hybrid duplexes. It was demonstrated that incorporation of diethylene glycol (miniPEG) at the gamma position of the peptide backbone increased the thermal stability of the hybrid duplexes (Sahu, B. et al. J. Org. Chem. 2011, 76, 5614-5627). Here, we applied atomic force microscopy (AFM) based single molecule force spectroscopy and dynamic force spectroscopy (DFS) to test the strength and stability of the hybrid 10 bp duplex. This hybrid duplex consisted of miniPEGgamma-PNA and DNA of the same length (gamma(MP)PNA-DNA), which we compared to a DNA duplex with a homologous sequence. AFM force spectroscopy data obtained at the same conditions showed that the gamma(MP)PNA-DNA hybrid is more stable than the DNA counterpart, 65 +/- 15 pN vs 47 +/- 15 pN, respectively. The DFS measurements performed in a range of pulling speeds analyzed in the framework of the Bell-Evans approach yielded a dissociation constant, koff ~ 0.030 +/- 0.01 s-1 for gamma(MP)PNA-DNA hybrid duplex vs 0.375 +/- 0.18 s-1 for the DNA-DNA duplex suggesting that the hybrid duplex is much more stable. Correlating the high affinity of gamma(MP)PNA DNA to slow dissociation kinetics is consistent with prior bulk characterization by surface plasmon resonance. Given the growing interest in gamma(MP)PNA as well as other synthetic DNA analogues, the use of single molecule experiments along with computational analysis of force spectroscopy data will provide direct characterization of various modifications as well as higher order structures such as triplexes and quadruplexes. PMID- 26898904 TI - Short and long time effects of low temperature Plasma Activated Media on 3D multicellular tumor spheroids. AB - This work investigates the regionalized antiproliferative effects of plasma activated medium (PAM) on colon adenocarcinoma multicellular tumor spheroid (MCTS), a model that mimics 3D organization and regionalization of a microtumor region. PAM was generated by dielectric barrier plasma jet setup crossed by helium carrier gas. MCTS were transferred in PAM at various times after plasma exposure up to 48 hours and effect on MCTS growth and DNA damage were evaluated. We report the impact of plasma exposure duration and delay before transfer on MCTS growth and DNA damage. Local accumulation of DNA damage revealed by histone H2AX phosphorylation is observed on outermost layers and is dependent on plasma exposure. DNA damage is completely reverted by catalase addition indicating that H2O2 plays major role in observed genotoxic effect while growth inhibitory effect is maintained suggesting that it is due to others reactive species. SOD and D mannitol scavengers also reduced DNA damage by 30% indicating that O(2)(-)* and OH* are involved in H2O2 formation. Finally, PAM is able to retain its cytotoxic and genotoxic activity upon storage at +4 degrees C or -80 degrees C. These results suggest that plasma activated media may be a promising new antitumor strategy for colorectal cancer tumors. PMID- 26898907 TI - Tobacco smoking and the risk of gallbladder disease. AB - Tobacco smoking has been inconsistently associated with gallbladder disease risk. To clarify the association we conducted a systematic review and meta-analysis of cohort studies published on the subject. We searched the PubMed and Embase databases for studies of smoking and gallbladder disease up to January 9th 2015. Prospective studies were included if they reported relative risk estimates and 95 % confidence intervals of gallbladder disease associated with current, former or ever smoking and by number of cigarettes per day. Summary relative risks were estimated by use of a random effects model. We identified ten prospective studies including 59,530 gallbladder disease cases among 4,213,482 participants that could be included in the meta-analysis. The summary RR was 1.19 (95 % CI 1.12 1.28, I(2) = 46.9 %, n = 6) for current smokers, 1.10 (95 % CI 1.07-1.13, I(2) = 0 %, n = 6) for former smokers and 1.15 (95 % CI 1.13-1.18, I(2) = 0 %, n = 7) for ever smokers. In the dose-response analysis the summary relative risk was 1.11 (95 % CI 1.08-1.14, I(2) = 33 %, n = 3) per 10 cigarettes per day and although there was indication of nonlinearity there was a dose-dependent positive association with increasing number of cigarettes smoked per day. The current meta analysis provides evidence of an increased risk of gallbladder disease associated with tobacco smoking. PMID- 26898908 TI - Predicting Parkinson disease in the community using a nonmotor risk score. AB - At present, there are no validated methods to identify persons who are at increased risk for Parkinson Disease (PD) from the general population. We investigated the clinical usefulness of a recently proposed non-motor risk score for PD (the PREDICT-PD risk score) in the population-based Rotterdam Study. At baseline (1990), we constructed a weighted risk score based on 10 early nonmotor features and risk factors in 6492 persons free of parkinsonism and dementia. We followed these persons for up to 20 years (median 16.1 years) for the onset of PD until 2011. We studied the association between the PREDICT-PD risk score and incident PD using competing risk regression models with adjustment for age and sex. In addition, we assessed whether the PREDICT-PD risk score improved discrimination (C-statistics) and risk classification (net reclassification improvement) of incident PD beyond age and sex. During follow-up, 110 persons were diagnosed with incident PD. The PREDICT-PD risk score was associated with incident PD (hazard ratio [HR] = 1.30; 95 % confidence interval [1.06; 1.59]) and yielded a small, non-significant improvement in overall discrimination (DeltaC statistic = 0.018[-0.005; 0.041]) and risk classification (net reclassification improvement = 0.172[-0.017; 0.360]) of incident PD. In conclusion, the PREDICT-PD risk score only slightly improves long-term prediction of PD in the community. PMID- 26898909 TI - Identification of Bacillus Probiotics Isolated from Soil Rhizosphere Using 16S rRNA, recA, rpoB Gene Sequencing and RAPD-PCR. AB - Some Bacillus species, especially Bacillus subtilis and Bacillus pumilus groups, have highly similar 16S rRNA gene sequences, which are hard to identify based on 16S rDNA sequence analysis. To conquer this drawback, rpoB, recA sequence analysis along with randomly amplified polymorphic (RAPD) fingerprinting was examined as an alternative method for differentiating Bacillus species. The 16S rRNA, rpoB and recA genes were amplified via a polymerase chain reaction using their specific primers. The resulted PCR amplicons were sequenced, and phylogenetic analysis was employed by MEGA 6 software. Identification based on 16S rRNA gene sequencing was underpinned by rpoB and recA gene sequencing as well as RAPD-PCR technique. Subsequently, concatenation and phylogenetic analysis showed that extent of diversity and similarity were better obtained by rpoB and recA primers, which are also reinforced by RAPD-PCR methods. However, in one case, these approaches failed to identify one isolate, which in combination with the phenotypical method offsets this issue. Overall, RAPD fingerprinting, rpoB and recA along with concatenated genes sequence analysis discriminated closely related Bacillus species, which highlights the significance of the multigenic method in more precisely distinguishing Bacillus strains. This research emphasizes the benefit of RAPD fingerprinting, rpoB and recA sequence analysis superior to 16S rRNA gene sequence analysis for suitable and effective identification of Bacillus species as recommended for probiotic products. PMID- 26898911 TI - Emerging techniques for ultrasensitive protein analysis. AB - Many important biomarkers for devastating diseases and biochemical processes are proteins present at ultralow levels. Traditional techniques, such as enzyme linked immunosorbent assays (ELISA), mass spectrometry, and protein microarrays, are often not sensitive enough to detect proteins with concentrations below the picomolar level, thus requiring the development of analytical techniques with ultrahigh sensitivities. In this review, we highlight the recent advances in developing novel techniques, sensors, and assays for ultrasensitive protein analysis. Particular attention will be focused on three classes of signal generation and/or amplification mechanisms, including the uses of nanomaterials, nucleic acids, and digital platforms. PMID- 26898913 TI - Bioengineering, Clinical and Therapeutical Trends in Transcatheter Aortic Valve Implantation. PMID- 26898912 TI - Sex and seasonal differences in neurogenesis and volume of the song-control system are associated with song in brood-parasitic and non-brood-parasitic icterid songbirds. AB - The song-control system in the brain of songbirds is important for the production and acquisition of song and exhibits both remarkable seasonal plasticity and some of the largest neural sex differences observed in vertebrates. We measured sex and seasonal differences in two nuclei of the song-control system of brood parasitic brown-headed cowbirds (Molothrus ater) and closely-related non parasitic red-winged blackbirds (Agelaius phoeniceus). These species differ in both the development and function of song. Brown-headed cowbirds have a larger sex difference in song than red-winged blackbirds. Female cowbirds never sing, whereas female blackbirds do though much less than males. In cowbirds, song primarily functions in mate choice and males modify their song as they approach sexual maturity and interact with females. In red-winged blackbirds, song is used primarily in territorial defence and is crystalized earlier in life. We found that the HVC was more likely to be discernable in breeding female blackbirds than in breeding female cowbirds. Compared to males, females had a smaller HVC and a smaller robust nucleus of the arcopallium (RA). However, females had higher doublecortin immunoreactivity (DCX+) in HVC, a measure of neurogenesis. Consistent with sex differences in song, the sex difference in RA volume was greater in cowbirds than in blackbirds. Males of both species had a smaller HVC with higher DCX+ in post-breeding condition than in breeding condition when song is more plastic. Sex and seasonal differences in the song-control system were closely related to variation in song in these two icterid songbirds. (c) 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1226-1240, 2016. PMID- 26898914 TI - Editorial: Sensory Science of Oral Health for Creating New Preventive Medicines. PMID- 26898910 TI - Phosphorylation of the amyloid beta-peptide at Ser26 stabilizes oligomeric assembly and increases neurotoxicity. AB - Aggregation and toxicity of the amyloid beta-peptide (Abeta) are considered as critical events in the initiation and progression of Alzheimer's disease (AD). Recent evidence indicated that soluble oligomeric Abeta assemblies exert pronounced toxicity, rather than larger fibrillar aggregates that deposit in the forms of extracellular plaques. While some rare mutations in the Abeta sequence that cause early-onset AD promote the oligomerization, molecular mechanisms that induce the formation or stabilization of oligomers of the wild-type Abeta remain unclear. Here, we identified an Abeta variant phosphorylated at Ser26 residue (pSer26Abeta) in transgenic mouse models of AD and in human brain that shows contrasting spatio-temporal distribution as compared to non-phosphorylated Abeta (npAbeta) or other modified Abeta species. pSer26Abeta is particularly abundant in intraneuronal deposits at very early stages of AD, but much less in extracellular plaques. pSer26Abeta assembles into a specific oligomeric form that does not proceed further into larger fibrillar aggregates, and accumulates in characteristic intracellular compartments of granulovacuolar degeneration together with TDP-43 and phosphorylated tau. Importantly, pSer26Abeta oligomers exert increased toxicity in human neurons as compared to other known Abeta species. Thus, pSer26Abeta could represent a critical species in the neurodegeneration during AD pathogenesis. PMID- 26898915 TI - Antiplatelet Therapy in TAVI: Current Clinical Practice and Recommendations. AB - Transcatheter aortic valve implantation (TAVI) is all the more used therapeutic option for patients suffering from symptomatic severe aortic valvular stenosis declined by surgeons because of high surgical risk. Given the high bleeding and ischemic risk of this vulnerable population, their antithrombotic treatment becomes a crucial issue. There is no consensus on antithrombotic treatment after TAVI and dual antiplatelet therapy (DAPT) with aspirin (indefinitely) and clopidogrel (1-6 months) is, in general, recommended. With regards to patients with an indication for oral anticoagulation (OAC), a combination of OAC plus aspirin or clopidogrel is commonly suggested. This review underscores that it is extremely difficult to compare different antithrombotic regimens in patients undergoing TAVI because of their variable demographic characteristics. Nevertheless, available data suggest that DAPT results to more bleeding events. Still, whether it positively affects ischemic episodes is doubtful. Ongoing trials are expected to draw a clearer picture on the field. PMID- 26898916 TI - Induced abortion in a Southern European region: examining inequalities between native and immigrant women. AB - OBJECTIVES: To examine induced abortion (IA) inequalities between native and immigrant women in a Southern European region and whether these inequalities depend on a 2010 Law facilitating IA. METHODS: We conducted two analyses: (1) prevalence of total IAs, repeat and second trimester IA, in native and immigrant women aged 12-49 years for years 2009-2013 according to country of origin; and (2) log-binomial regression was used to quantify the association of place of origin with repeat and second trimester IAs among women with IAs. RESULTS: Immigrants were more likely to have an IA than Spanish women, with the highest probability in Sub-Saharan Africa (PR 8.32 95 % CI 3.66-18.92). Immigrant women with an IA from countries other than Maghreb and Asia have higher probabilities of a repeat IA than women from Spain. Women from Europe non-EU/Romania were 50 % (95 % CI 0.30-0.79) less likely to have a second trimester IA, while women from Central America/Caribbean were 45 % (95 % CI 1.11-1.89) more likely than Spanish women. The 2010 Law did not affect these associations. CONCLUSIONS: There is a need for parenthood planning programs and more information and access to contraception methods especially in immigrant women to help decrease IAs. PMID- 26898918 TI - Radiation-resistant B-1 cells: A possible initiating cells of neoplastic transformation. AB - The role of B-1 cells in the hyperproliferative hematologic disease has been described. Several reports bring evidences that B-1 cells are the main cell population in the chronic lymphatic leukemia. It is also described that these cells have an important involvement in the lupus erythematous systemic. The murine model used to investigate both disease models is NZB/NZW. Data from literature point that mutation in micro-RNA 15a and 16 are the responsible for the B-1 hyperplasia in these mice. Interestingly, it was demonstrated that NZB/NZW B-1 cells are radioresistant, contrariwise to observe in other mouse lineage derived B-1 cells and B-2 cells. However, some reports bring evidences that a small percentage of B-1 cells in healthy mice are also able to survive to irradiation. Herein, we aim to investigate the malignant potential of ionizing radiation resistant B-1 cells in vitro. Our main goal is to establish a model that mimics the neoplastic transformation originate to a damage exposure of DNA, and not only related to intrinsic mutations. Data shown here demonstrated that radiation-resistant B-1 cells were able to survive long periods in culture. Further, these cells show proliferation index increase in relation to non irradiated B-1 cells. In addition, radiation resistant B-1 cells showed hyperploid, morphologic alterations, increased induction of apoptosis after anti IgM stimulation. Based on these results, we could suggest that radiation resistant B-1 cells showed some modifications in that could be related to induction of malignant potential. PMID- 26898917 TI - Host kinin B1 receptor plays a protective role against melanoma progression. AB - Melanoma is a very aggressive tumor that arises from melanocytes. Late stage and widely spread diseases do not respond to standard therapeutic approaches. The kallikrein-kinin system (KKS) participates in biological processes such as vasodilatation, pain and inflammatory response. However, the role of KKS in tumor formation and progression is not completely understood. The role of the host kinin B1 receptor in melanoma development was evaluated using a syngeneic melanoma model. Primary tumors and metastasis were respectively induced by injecting B16F10 melanoma cells, which are derived from C57BL/6 mice, subcutaneously or in the tail vein in wild type C57BL/6 and B1 receptor knockout mice (B1(-/-)). Tumors developed in B1(-/-) mice presented unfavorable prognostic factors such as increased incidence of ulceration, higher levels of IL-10, higher activation of proliferative pathways such as ERK1/2 and Akt, and increased mitotic index. Furthermore, in the metastasis model, B1(-/-) mice developed larger metastatic colonies in the lung and lower CD8(+)immune effector cells when compared with WT animals. Altogether, our results provide evidences that B1(-/-) animals developed primary tumors with multiple features associated with poor prognosis and unfavorable metastatic onset, indicating that the B1 receptor may contribute to improve the host response against melanoma progression. PMID- 26898919 TI - Digital Carotid Compression: A Simple Method to Reduce Solid Cerebral Emboli During Cardiac Surgery. AB - OBJECTIVES: Serious neurologic injury can be attributed to embolization of solid particles into cerebral vessels during cardiac surgery. Previous studies using transcranial Doppler (TCD) identified arterial cannulation and aortic declamping to be associated with cerebral embolization. The purpose of this study was to investigate the impact of transient compression of the carotid arteries during these maneuvers on the embolic load during cardiac surgery with cardiopulmonary bypass. DESIGN: Prospective, randomized, clinical trial/pilot study. SETTING: Single-center study at a university hospital. PARTICIPANTS: Patients with multiple types of procedures were included and they were prospectively, randomly assigned to group I (n = 20, carotid compression during arterial cannulation and aortic declamping) and group II (n = 20, no carotid compression). INTERVENTIONS: Bilateral continuous monitoring of the middle cerebral arteries was performed with a multirange, multifreqency transcranial Doppler (DopplerBoxX, DWL, Singen, Germany), allowing for discrimination between solid and gaseous emboli. For aortic cannulation the carotid arteries were compressed for 5 seconds and for declamping for 3 seconds, and microemboli signals were detected within the following 45 seconds. MEASUREMENTS AND MAIN RESULTS: A reduction of intraoperative solid emboli was detected in group I compared with group II (26+/ 16 v 38+/-18; p = 0.04). Looking specifically at the maneuver of arterial cannulation, the observed difference was 0.5+/-0.8 in group I versus 5.7+/-5.8 in group II (p<0.0001). During aortic declamping, 6.6+/-6.2 emboli were encountered in group I and 10.8+/-5.2 in group II (p = 0.02). The incidence of neurologic events was not significantly different between groups (2 patients in group II had pathologic changes on magnetic resonance imaging). CONCLUSIONS: The data of this preliminary trial demonstrated that transient compression of the carotid arteries during arterial cannulation and aortic declamping led to a decreased number of solid cerebral emboli. Further prospective, randomized clinical studies should be undertaken to investigate the influence of transient carotid artery compression during specific surgical procedures. PMID- 26898920 TI - Guidewire Entrapment in the Chiari Network. PMID- 26898921 TI - Monitoring the Transmembrane Proton Gradient Generated by Cytochrome bo3 in Tethered Bilayer Lipid Membranes Using SEIRA Spectroscopy. AB - Membrane proteins act as biocatalysts or ion/proton pumps to convert and store energy from ubiquitous environmental sources. Interfacing these proteins to electrodes allows utilizing the energy for enzymatic biofuel cells or other auspicious biotechnological applications. To optimize the efficiency of these devices, appropriate membrane models are required that ensure structural and functional integrity of the embedded enzymes and provide structural insight. We present a spectroelectrochemical surface-enhanced infrared absorption (SEIRA) and electrical impedance spectroscopy (EIS) study of the bacterial respiratory ubiquinol/cytochrome bo3 (cyt bo3) couple incorporated into a tethered bilayer lipid membrane (tBLM). Here, we employed a new lipid tether (WK3SH, dihydrocholesteryl (2-(2-(2-ethoxy)ethoxy)ethanethiol), which was synthesized using a three-step procedure with very good yield and allowed measuring IR spectra without significant spectral interference of the tBLM. The functional integrity of the incorporated cyt bo3 was demonstrated by monitoring the enzymatic O2 reduction current and the formation of the transmembrane proton gradient. Based on a SEIRA-spectroscopic redox titration, a shift of the pH dependent redox potential of the ubiquinones under turnover conditions was correlated with an alkalinization of the submembrane reservoir by +0.8 pH units. This study demonstrates the high potential of tBLMs and the SEIRA spectroscopic approach to study bioenergetic processes. PMID- 26898922 TI - Assessment of vitamin D levels in type 1 and type 2 diabetes patients: Results from metaanalysis. AB - SCOPE: Accumulating evidence indicates that vitamin D deficiency is prevalent in patients with type 1 (T1D) and type 2 diabetes (T2D). The present study aims to assess 25-hydroxyvitamin D [25(OH)D] levels in T1D and T2D patients compared with controls through a metaanalysis. METHODS AND RESULTS: We searched databases for articles published until January 2015. A total of 12 studies covering 2003 patients and 1882 controls and 11 studies covering 2236 patients and 2438 controls were included to metaanalyze 25(OH)D levels in patients with T1D and T2D, respectively. Pooled data showed that T1D patients had lower levels of 25(OH)D than controls (summary standardized mean difference (SMD) -0.70, 95% confidence interval (CI) -1.02 to -0.37). Further age-subgroup analysis found that 25(OH)D levels in T1D patients was also significantly lower than controls in subgroup aged <= 14 years (summary SMD -1.04, 95% CI -1.55 to -0.53), while the association is not statistically significant in the subgroup aged > 14 years. Similarly, T2D patients had lower 25(OH)D levels compared with controls (summary SMD -0.58, 95%CI -1.16 to -0.00). CONCLUSION: Available data indicated that both T1D and T2D patients had lower levels of 25(OH)D than controls overall. The mechanistic underpinnings of this association warrant further elucidation. PMID- 26898923 TI - An Alternative Surgical Method for Treatment of Osteoid Osteoma. AB - BACKGROUND An osteoid osteoma is a benign bone tumor that tends to be <1 cm in size. The tumor is characterized by night-time pain that may be relieved by aspirin or other non-steroidal anti-inflammatory drugs. Osteoid osteoma can be treated with various conservative and surgical methods, but these have some risks and difficulties. The purpose of the present study was to present an alternative treatment method for osteoid osteoma and the results we obtained. MATERIAL AND METHODS In the period from 2010 to 2014, 10 patients with osteoid osteoma underwent nidus excision by using a safe alternative method in an operating room (OR) with no computed tomography (CT). The localization of the tumor was determined by use of a CT-guided Kirschner wire in the radiology unit, then, in the OR the surgical intervention was performed without removing the Kirschner wire. RESULTS Following the alternative intervention, all the patients were completely relieved of pain. In the follow-up, no recurrence or complication occurred. CONCLUSIONS The presented alternative method for treating osteoid osteoma is an efficient and practical procedure for surgeons working in clinics that lack specialized equipment. PMID- 26898924 TI - The effects of the centrifugation speed on the survival of autogenous fat grafts in a rat model. AB - Purpose The most important problem in fat transplantation is the durability, which is closely associated with the applied technique. This study includes the comparison of different centrifugation speeds on the survival of autogenous fat grafts in rats. Materials and methods Forty-nine Sprague-Dawley rats were divided into seven groups and the left inguinal fat pad was extracted and re-implanted under the scalp after performing appropriate preparation processes. In the first group the fatty tissue was re-implanted in en-bloc fashion and in the second group it was re-implanted after trimming. After trimming, centrifugation with a G force of 111.8 (1000 rpm) was performed in the third group, 447.2 (2000 rpm) in the fourth group, 1006.2 (3000 rpm) in the fifth group, 1788.8 (4000 rpm) in the sixth group, and 2795 (5000 rpm) in the seventh group for 4 minutes. The fat grafts were taken after 3 months and histopathological and statistical evaluations were performed. Results The rate of viable fat grafts was significantly higher in the 4th and 5th groups comparing to the first three groups. Total weight and volume amounts of the 4th and 5th groups were also significantly higher comparing to the first three groups. Conclusion Maximal long term durability and fat cell viability results were obtained in the groups with 2000 rpm or 447.2 G-force/4 minutes and 3000 rpm or 1006.2 G-force/4 minutes centrifugation speed, indicating that 4 minutes centrifugation with an average G force of 698.75 or 2500 rpm provides the best results for the survival of autogenous fat grafts. PMID- 26898925 TI - Adenosine metabolism of human mesenchymal stromal cells isolated from patients with head and neck squamous cell carcinoma. AB - BACKGROUND: Mesenchymal stromal cells (MSC) are a major component of the tumor microenvironment in patients with head and neck squamous cell carcinoma (HNSCC). MSC display innate and regulatory immunologic functions, very similar to many hematopoietic 'classical' immune cells. Conversion of ATP to immunosuppressive adenosine is an immunosuppressive mechanism utilized by other hematopoietic immune cells. The present study explores the adenosine metabolism of tumor derived MSC in comparison to autologous MSC from non-malignant tissue. METHODS: From HNSCC patients (n=10), paired MSC were generated from tumor tissue (tMSC) and autologous healthy control tissue (cMSC). Differentiation properties and phenotype (CD105, CD73, CD39, CD90, CD26, CD29) were compared by flow cytometry. Production of immunosuppressive adenosine (ADO) by functionally active ectonucleotidases, CD39 and CD73, was determined by luminescence and mass spectrometry. Suppressive activity of ADO was tested in CFSE proliferation assays of isolated T-cells. Plasticity of cMSC was explored after incubation with tumor cell conditioned media. RESULTS: Differentiation into osteogenic, chondrogenic and adipogenic directions was comparable in tMSC and cMSC. Expression of ectonucleotidases, CD39 and CD73, was decreased in tMSC as compared to corresponding cMSC, which correlated with decreased ATP metabolism in mass spectrometry. Proliferation of CD4+ T-cells was significantly suppressed by exogenous ADO. Tumor-conditioned medium was unable to down-regulate ADO production in cMSC. CONCLUSION: We identified MSC of the oropharyngeal mucosa as an important producer of exogenous ADO. In patients with HNSCC, reduced expression of ADO may contribute to excessive inflammation and tumor growth. PMID- 26898926 TI - High-level expression and characterization of the Bacillus subtilis subsp. subtilis str. BSP1 YwaD aminopeptidase in Pichia pastoris. AB - Aminopeptidases are widely used for creating protein hydrolysates and peptide sequencing. The ywaD gene from a new Bacillus isolate, named Bacillus subtilis subsp. subtilis str. BSP1, was cloned into the yeast expression vector pHBM905A and expressed and secreted by Pichia pastoris strain GS115. The deduced amino acid sequence of the aminopeptidase encoded by the ywaD gene shared up to 98% identity with aminopeptidases from B. subtilis strains 168 and zj016. The yield (3.81 g/l) and specific activity (788 U/mg) of recombinant YwaD in high-density fermentation were extremely high. And 829.83 mg of the purified enzyme (4089.72 U/mg) were harvested. YwaD was glycosylated, and its activity decreased after deglycosylation, which was similar to that of the aminopeptidase from B. subtilis strain zj016. YwaD was most active toward l-arginine-4-nitroanilide. Moreover, it exhibited high resistance to carbamide, which was not true for aminopeptidases from B. subtilis strains 168 and zj016, which could simplify the purification of YwaD. Moreover, the expression and parts of characterization of the aminopeptidase from B. subtilis strain 168 in Pichia pastoris were added as supplementary material. The sequence and other characteristics of YwaD were compared with those of aminopeptidases from B. subtilis strains 168 and zj016, and they will provide a solid foundation for further research on the influence of amino acid mutations on the function of aminopeptidases. PMID- 26898927 TI - Ethanol concentrations in the human gastrointestinal tract after intake of alcoholic beverages. AB - INTRODUCTION: The goal of this study was to monitor gastric and duodenal ethanol concentrations arising from the consumption of commonly used alcoholic beverages. MATERIALS AND METHODS: In a cross-over study, five fasting volunteers were asked to drink two standard consumptions of commercially available alcoholic beverages, including beer (Stella Artois(r), 500 mL, 5.2% ethanol), wine (Blanc du Blanc(r), 200 mL, 11% ethanol) and whisky (Gallantry Whisky(r), 80 mL, 40% ethanol). The volunteers finished drinking beer within 10 min and wine or whisky within 5 min. Ethanol concentrations in gastric and duodenal fluids, aspirated as a function of time, were analyzed by headspace gas chromatography. RESULTS: In all three conditions, the average gastric profile shows a maximum ethanol concentration (Cmax) at 7 min, while the mean duodenal profiles have a Tmax at 20, 7 and 12 min for beer, wine and whisky, respectively. The median gastric ethanol Cmax (min max) for the beer, wine and whisky conditions amounts to 4.1% (3.1-4.1), 4.1% (2.6-7.3) and 11.4% (6.3-21.1), respectively. The mean duodenal profiles follow the same pattern as their corresponding gastric profiles, albeit with lower percentages of ethanol. Median duodenal ethanol Cmax (min-max) for beer, wine and whisky are 1.97% (0.89-4.3), 2.39% (2.02-5.63) and 5.94% (3.55-17.71), respectively. Intraluminal ethanol concentrations appear to decline relatively rapidly in fasting conditions: both stomach and duodenum contained less than 0.05% of ethanol after 120 min. CONCLUSIONS: This in vivo study is the first to present intraluminal ethanol concentrations in man after the intake of alcoholic beverages. Relatively low and fast declining gastric ethanol concentrations were observed, contrasting with the current Food and Drug Administration guidelines for the in vitro testing of formulations with respect to ethanol resistance. The presented gastric and duodenal ethanol concentrations and their variation may serve as reference data to design relevant models for predicting (i) ethanol resistance of drug formulations and (ii) ethanol effects on drug solubility and permeability. PMID- 26898928 TI - Mercury speciation, distribution, and bioaccumulation in a river catchment impacted by compact fluorescent lamp manufactures. AB - The influence from the manufacturing of compact fluorescent lamps (CFL) on mercury (Hg) speciation and distribution in river catchments nearby a typical CFL manufacturing area in China was investigated. Water, sediment, river snail (Procambarus clarkii), and macrophyte (Paspalum distichum L.) samples were collected. Total Hg (THg) and methylmercury (MeHg) concentrations in water ranged from 1.06 to 268 ng . L(-1) and N.D. -2.14 ng . L(-1), respectively. MeHg was significantly positively correlated with THg in water. THg and MeHg in sediment ranged from 15.0 to 2480 and 0.06 to 1.85 ng . g(-1), respectively. River snail samples exhibited high concentrations of THg (206-1437 ng . g(-1)) and MeHg (31.4 404 ng . g(-1)). THg and MeHg concentrations in root of P. distichum L. were significantly higher than those in shoot, indicating that THg and MeHg in the plant were mainly attributed to root assimilation. A very high bioaccumulation factor (20.9 +/- 22.1) for MeHg in P. distichum L was noted, suggesting that P. distichum L. might have a potential role in phytoremediating MeHg contaminated soil due to its abnormal uptake capacity to MeHg. PMID- 26898929 TI - Estimation of long-term Ca(2+) loss through outlet flow from an agricultural watershed and the influencing factors. AB - Soil Ca(2+) loss from agricultural lands through surface runoff can accelerate soil acidification and render soil degradation, but the characteristics of Ca(2+) loss and influencing factors in watershed scale are unclear. This study was carried out in a watershed with various land uses in a subtropical region of China. The outlet flow was automatically monitored every 5 min all year round, and the water samples were collected twice a year from 2001 to 2011. The concentrations of Ca(2+), Mg(2+), K(+), total nitrogen (TN), and total phosphorus (TP) of water samples were measured. The dynamic losses of the nutrients through the outlet flow were estimated, and the relationships between the nutrient losses and rainfall intensity as well as antecedent soil moisture were investigated. The results showed that great variations of nutrient concentrations and losses appeared during the investigation period. The average concentrations of Ca(2+), Mg(2+), K(+), TN, and TP were 0.43, 0.08, 0.10, 0.19, and 0.003 mmol L(-1), respectively. The average Ca(2+) loss reached 1493.79 mol ha(-1) year(-1) and was several times higher than for Mg(2+), K(+), and TN, about 140 times higher than for TP. Rainfall intensity had remarkable effects on Ca(2+) concentration (P < 0.01) and loss (P < 0.05) when it reached rainstorm level (50 mm day(-1)), while a quadratic relationship was observed between antecedent soil moisture and Ca(2+) concentration only when rainfall intensity was less than 50 mm day(-1). In a word, much greater amounts of Ca(2+) were lost from the watershed, and this may be one important contributor to the increasing acidification of acidic soils in subtropical regions. PMID- 26898930 TI - Low birth weight of Vietnamese infants is related to their mother's dioxin and glucocorticoid levels. AB - We aimed to determine the relationship between dioxin congeners in maternal breast milk and maternal glucocorticoid levels with newborn birth weight after nearly 45 years of use of herbicides in the Vietnam War. The study subjects comprised 58 mother-infant pairs in a region with high dioxin levels in the soil (hotspot) and 62 pairs from a control region. Dioxin levels in maternal breast milk were measured by HRGC-HRMS. Salivary glucocorticoid levels were determined by LC-MS/MS. Dioxin congener levels in mothers from the hotspot were found to be two to fivefold higher than those in mothers from the control region. Birth weight was inversely correlated with 2,3,7,8-TeCDD and 2,3,4,7,8-PeCDF congener levels. The rate of newborns whose birth weight was less than 2500 g was threefold higher in the hotspot (12 %) than in the control region (4 %). Salivary glucocorticoid levels in mothers with low birth weight infants were significantly higher than those in the normal birth weight group. Low birth weight of Vietnamese newborns in a hotspot for dioxin levels is related to some dioxin congener levels and high glucocorticoid levels in mothers. This finding in mother infant pairs suggests that excess maternal glucocorticoid levels are related to dioxin burden and they result in low birth weight. PMID- 26898931 TI - Changes on fecal microbiota in rats exposed to permethrin during postnatal development. AB - Alteration of the gut microbiota through diet and environmental contaminants may disturb the mammalian digestive system, leading to various diseases. Because most exposure to environmentally pyrethroid pesticides such as permethrin (PERM) occurs through the diet, the commensal gut microbiota is likely to be exposed to PERM. The study aimed at evaluating the effect of low-dose exposure to PERM in early life on the composition of fecal microbiota in rats. Over a 4-month follow up period, fecal microbiota and short-chain fatty acids were measured in order to identify possible differences between PERM-treated rats and controls. Further in vitro antimicrobial experiments were conducted to establish the antibacterial activity of PERM against different strains to obtain Minimal Inhibitory Concentrations. The main finding focused on the reduced abundance of Bacteroides Prevotella-Porphyromonas species, increased Enterobacteriaceae and Lactobacillus in PERM-treated rats compared to controls. Changes of acetic and propionic acid levels were registered in PERM-treated group. From in vitro studies, PERM showed higher antibacterial activity against beneficial bacteria such as Bifidobacterium and Lactobacillus paracasei, while to inhibit potential pathogens as Staphylococcus aureus and Escherichia coli PERM concentration needed to be increased. In summary, exposure to PERM could affect the fecal microbiota and could be a crucial factor contributing to the development of diseases. PMID- 26898932 TI - Impacts of low-molecular-weight organic acids on aquatic behavior of graphene nanoplatelets and their induced algal toxicity and antioxidant capacity. AB - Knowledge of the interaction between graphene-based materials and low-molecular weight organic acids (LOAs) is essential to understand fate and effects of graphene-based materials in the aquatic environment, but this interaction remains poorly elucidated. In this study, the effects of LOAs on the physicochemical properties of graphene nanoplatelets (GNPs) in an aqueous medium and on the GNP toxicity to algae were studied. The unicellular green alga Scenedesmus obliquus was exposed to GNP suspensions in the presence of benzoic acid or gallic acid at various concentrations. The GNPs had smaller hydrodynamic sizes and the GNP suspensions were more stable and had higher or lower surface zeta potentials in the presence of LOAs than when LOAs were not present. The toxic effects in S. obliquus cultures incubated with GNP suspensions containing LOAs were related to the LOA concentration, and the presence of LOAs caused three effects: stimulation, alleviation, and synergistic inhibition. The intensities of the effects mainly correlated with the LOA concentration, the extent of agglomeration, and particle-induced oxidative stress. The results indicate that the environmental fates and toxicities of GNPs are strongly affected by the binding of GNPs to LOAs. PMID- 26898933 TI - Spatiotemporal analysis for the effect of ambient particulate matter on cause specific respiratory mortality in Beijing, China. AB - This study explored the association between particulate matter with an aerodynamic diameter of less than 10 MUm (PM10) and the cause-specific respiratory mortality. We used the ordinary kriging method to estimate the spatial characteristics of ambient PM10 at 1-km * 1-km resolution across Beijing during 2008-2009 and subsequently fit the exposure-response relationship between the estimated PM10 and the mortality due to total respiratory disease, chronic lower respiratory disease, chronic obstructive pulmonary disease (COPD), and pneumonia at the street or township area levels using the generalized additive mixed model (GAMM). We also examined the effects of age, gender, and season in the stratified analysis. The effects of ambient PM10 on the cause-specific respiratory mortality were the strongest at lag0-5 except for pneumonia, and an inter-quantile range increase in PM10 was associated with an 8.04 % (95 % CI 4.00, 12.63) increase in mortality for total respiratory disease, a 6.63 % (95 % CI 1.65, 11.86) increase for chronic lower respiratory disease, and a 5.68 % (95 % CI 0.54, 11.09) increase for COPD, respectively. Higher risks due to the PM10 exposure were observed for females and elderly individuals. Seasonal stratification analysis showed that the effects of PM10 on mortality due to pneumonia were stronger during spring and autumn. While for COPD, the effect of PM10 in winter was statistically significant (15.54 %, 95 % CI 5.64, 26.35) and the greatest among the seasons. The GAMM model evaluated stronger associations between concentration of PM10. There were significant associations between PM10 and mortality due to respiratory disease at the street or township area levels. The GAMM model using high-resolution PM10 could better capture the association between PM10 and respiratory mortality. Gender, age, and season also acted as effect modifiers for the relationship between PM10 and respiratory mortality. PMID- 26898934 TI - Spatio-temporal variation of erosion-type non-point source pollution in a small watershed of hilly and gully region, Chinese Loess Plateau. AB - Loss of nitrogen and phosphorus in the hilly and gully region of Chinese Loess Plateau not only decreases the utilization rate of fertilizer but also is a potential threat to aquatic environments. In order to explore the process of erosion-type non-point source (NPS) pollution in Majiagou watershed of Loess Plateau, a distributed, dynamic, and integrated NPS pollution model was established to investigate impacts of returning farmland on erosion-type NPS pollution load from 1995 to 2012. Results indicate that (1) the integrated model proposed in this study was verified to be reasonable; the general methodology is universal and can be applicable to the hilly and gully region, Loess Plateau; (2) the erosion-type NPS total nitrogen (TN) and total phosphorus (TP) load showed an overall decreasing trend; the average nitrogen and phosphorus load modulus in the last four years (2009-2012) were 1.23 and 1.63 t/km(2) . a, respectively, which were both decreased by about 35.4 % compared with the initial treatment period (1995-1998); and (3) The spatial variations of NPS pollution are closely related to spatial characteristics of rainfall, topography, and soil and land use types; the peak regions of TN and TP loss mainly occurred along the main river banks of the Yanhe River watershed from northeast to southeast, and gradually decreased with the increase of distance to the left and right river banks, respectively. Results may provide scientific basis for the watershed-scale NPS pollution control of the Loess Plateau. PMID- 26898935 TI - The relationship between carbon dioxide and agriculture in Ghana: a comparison of VECM and ARDL model. AB - In this paper, the relationship between carbon dioxide and agriculture in Ghana was investigated by comparing a Vector Error Correction Model (VECM) and Autoregressive Distributed Lag (ARDL) Model. Ten study variables spanning from 1961 to 2012 were employed from the Food Agricultural Organization. Results from the study show that carbon dioxide emissions affect the percentage annual change of agricultural area, coarse grain production, cocoa bean production, fruit production, vegetable production, and the total livestock per hectare of the agricultural area. The vector error correction model and the autoregressive distributed lag model show evidence of a causal relationship between carbon dioxide emissions and agriculture; however, the relationship decreases periodically which may die over-time. All the endogenous variables except total primary vegetable production lead to carbon dioxide emissions, which may be due to poor agricultural practices to meet the growing food demand in Ghana. The autoregressive distributed lag bounds test shows evidence of a long-run equilibrium relationship between the percentage annual change of agricultural area, cocoa bean production, total livestock per hectare of agricultural area, total pulses production, total primary vegetable production, and carbon dioxide emissions. It is important to end hunger and ensure people have access to safe and nutritious food, especially the poor, orphans, pregnant women, and children under-5 years in order to reduce maternal and infant mortalities. Nevertheless, it is also important that the Government of Ghana institutes agricultural policies that focus on promoting a sustainable agriculture using environmental friendly agricultural practices. The study recommends an integration of climate change measures into Ghana's national strategies, policies and planning in order to strengthen the country's effort to achieving a sustainable environment. PMID- 26898936 TI - Experimental study on copper uptake capacity in the Mediterranean mussel (Mytilus galloprovincialis). AB - To investigate the effect of different sizes, sex, and exposure time on Cu uptake capacity, mussels Mytilus galloprovincialis of different shell sizes were exposed to different Cu concentrations in different aquariums. In another experiment, mussels were exposed to stable dissolved Cu for 6 days in the laboratory. All mussels tissue concentrations were analyzed using energy dispersive X-ray fluorescence (EDXRF) spectrometry. At the end of uptake, the rate of increase of Cu level in the soft tissues of mussels in different aquariums was 3.84-7.92 times higher than before exposure. While the results of Cu concentrations were negatively correlated with the shell sizes in the control and second groups (r control = -0.862, r second = -0.851 p < 0.05), this relation was not observed in the other groups (p > 0.05). Also, results showed no significant difference between male and female (p > 0.05). On the other hand, Cu concentration values in soft tissue were monitored daily and observed to be increasing up to the third day but afterwards to be descending, thus indicating a significant effect of the exposure time-related Cu uptake by mussels. Therefore, the exposure time to Cu metal of the mussel should be taken into account in the marine pollution investigations. In addition, by using the obtained Cu heavy metal concentration results, the heavy metal intake by the human population was calculated by taking into account daily mussel consumption. The results were examined for potential human health risks and discussed. These results would be helpful to understand factors controlling Cu accumulation in mussels. PMID- 26898937 TI - Novel fusion transcripts in bladder cancer identified by RNA-seq. AB - Urothelial carcinoma (UC) is the most common type of bladder cancer and is the second most frequently diagnosed genitourinary tumor. The identification of fusion genes in bladder cancer might provide new perspectives for its classification and significance. In this study, we present a thorough search on three UC samples for novel fusion transcripts in bladder cancer using high throughput RNA sequencing. We used stringent requirements for 819 fusion candidates and nominated 10 candidate fusion transcripts. Among them four novel fusion genes SEPT9/CYHR, IGF1R/TTC23, SYT8/TNNI2 and CASZ1/DFFA were validated and characterized in 48 formalin-fixed paraffin-embedded (FFPE) specimens of bladder cancer. Chromosomal rearrangements of regions 17q25, 15q26.3 and 1p36.22 resulting in the fusion transcripts SEPT9/CYHR, IGF1R/TTC23 and CASZ1/DFFA, appeared to be rare or unique events because they were not detected in the 48 UC samples. In contrast, the SYT8/TNNI2 fusion transcript resulting from transcription-induced chimerism by read-through mechanisms was a rather common and tumor-specific event occurring in 37.5% (18/48) of the UC specimens. Further investigation of functional and clinical relevance of novel fusion genes remains to be elucidated to reveal their role in bladder carcinogenesis. PMID- 26898939 TI - LincRNA-ROR promotes invasion, metastasis and tumor growth in pancreatic cancer through activating ZEB1 pathway. AB - Pancreatic cancer (PC) remains one of the most lethal malignant tumors; early distant metastasis commonly results in poor prognosis. Recent studies confirmed the pivotal role of the long non-coding RNAs (lncRNAs) in tumorigenesis and metastasis of malignant tumors, including PC. However, little is known about the role of LincRNA-ROR (linc-ROR) in PC. In the present study, we found that linc ROR was upregulated in PC tissues. Overexpression of linc-ROR promoted cells proliferation, migration, invasion and metastasis both in vitro and in a mouse model. Contrarily, knockdown of linc-ROR attenuated proliferation, invasion and distant metastasis. Mechanistically, we confirmed that linc-ROR up-regulates ZEB1 and then induces epithelial-mesenchymal transition (EMT), which promotes the aggressive biological behaviors of PC. Together, these results indicate that linc ROR acts as an important regulator of ZEB1, can promote invasion and metastasis in PC, and may represent a novel therapeutic target. PMID- 26898940 TI - Muscle from a 20-week-old myotubular myopathy fetus is not myotubular. PMID- 26898942 TI - Directed evolution of leucine dehydrogenase for improved efficiency of L-tert leucine synthesis. AB - L-tert-Leucine and its derivatives are used as synthetic building blocks for pharmaceutical active ingredients, chiral auxiliaries, and ligands. Leucine dehydrogenase (LeuDH) is frequently used to prepare L-tert-leucine from the alpha keto acid precursor trimethylpyruvate (TMP). In this study, a high-throughput screening method for the L-tert-leucine synthesis reaction based on a spectrophotometric approach was developed. Directed evolution strategy was applied to engineer LeuDH from Lysinibacillus sphaericus for improved efficiency of L-tert-leucine synthesis. After two rounds of random mutagenesis, the specific activity of LeuDH on the substrate TMP was enhanced by more than two-fold, compared with that of the wild-type enzyme, while the activity towards its natural substrate, leucine, decreased. The catalytic efficiencies (k cat/K m) of the best mutant enzyme, H6, on substrates TMP and NADH were all enhanced by more than five-fold as compared with that of the wild-type enzyme. The efficiency of L tert-leucine synthesis by mutant H6 was significantly improved. A productivity of 1170 g/l/day was achieved for the mutant enzyme H6, compared with 666 g/l/day for the wild-type enzyme. PMID- 26898938 TI - Mucins and associated glycan signatures in colon adenoma-carcinoma sequence: Prospective pathological implication(s) for early diagnosis of colon cancer. AB - Development of biomarkers that detect early stage resectable premalignant lesions of colon can provide critical aid in the prevention of colorectal cancer. Recent lines of evidence suggest the utility of mucin expression to predict malignant transformation of colon pre-neoplastic lesions. In this study, we investigated the combined expression of multiple mucins and mucin-associated glycans during the adenoma-carcinoma sequence of colon cancer progression. Further, we evaluated their applicability as markers for differentiating adenomas/adenocarcinomas from hyperplastic polyps. Immunohistochemical analyses performed on colon disease tissue microarrays revealed downregulation of MUC2 and MUC4 expression (p < 0.0001) while MUC1 and MUC5AC expressions were upregulated (p = 0.01) during adenoma-adenocarcinoma progression. Expression of MUC17 was downregulated in inflamed tissues compared to normal tissues, but its increased expression differentiated adenomas (p = 0.0028) and adenocarcinomas (p = 0.025) from inflammation. Glycan epitope-Tn/STn on MUC1 showed higher expression in hyperplastic polyps (p = 0.023), adenomas (p = 0.042) and adenocarcinomas (p = 0.0096) compared to normal tissues. Multivariate regression analyses indicated that a combination of MUC2, MUC5AC, and MUC17 could effectively discriminate adenoma-adenocarcinoma from hyperplastic polyps. Altogether, a combined analysis of altered mucins and mucin-associated glycans is a useful approach to distinguish premalignant/malignant lesions of colon from benign polyps. PMID- 26898944 TI - Non-ionizing radiofrequency electromagnetic waves traversing the head can be used to detect cerebrovascular autoregulation responses. AB - Monitoring changes in non-ionizing radiofrequency electromagnetic waves as they traverse the brain can detect the effects of stimuli employed in cerebrovascular autoregulation (CVA) tests on the brain, without contact and in real time. CVA is a physiological phenomenon of importance to health, used for diagnosis of a number of diseases of the brain with a vascular component. The technology described here is being developed for use in diagnosis of injuries and diseases of the brain in rural and economically underdeveloped parts of the world. A group of nine subjects participated in this pilot clinical evaluation of the technology. Substantial research remains to be done on correlating the measurements with physiology and anatomy. PMID- 26898945 TI - Recent Progress in Materials and Devices toward Printable and Flexible Sensors. AB - Printable electronics present a new era of wearable electronic technologies. Detailed technologies consisting of novel ink semiconductor materials, flexible substrates, and unique processing methods can be integrated to create flexible sensors. To detect various stimuli of the human body, as well as specific environments, unique electronic devices formed by "ink-based semiconductors" onto flexible and/or stretchable substrates have become a major research trend in recent years. Materials such as inorganic, organic, and hybrid semiconductors with various structures (i.e., 1D, 2D and 3D) with printing capabilities have been considered for bio and medical applications. In this review, we report recent progress in materials and devices for future wearable sensor technologies. PMID- 26898943 TI - Interplay of histidine residues of the Alzheimer's disease Abeta peptide governs its Zn-induced oligomerization. AB - Conformational changes of Abeta peptide result in its transformation from native monomeric state to the toxic soluble dimers, oligomers and insoluble aggregates that are hallmarks of Alzheimer's disease (AD). Interactions of zinc ions with Abeta are mediated by the N-terminal Abeta(1-16) domain and appear to play a key role in AD progression. There is a range of results indicating that these interactions trigger the Abeta plaque formation. We have determined structure and functional characteristics of the metal binding domains derived from several Abeta variants and found that their zinc-induced oligomerization is governed by conformational changes in the minimal zinc binding site 6HDSGYEVHH14. The residue H6 and segment 11EVHH14, which are part of this site are crucial for formation of the two zinc-mediated interaction interfaces in Abeta. These structural determinants can be considered as promising targets for rational design of the AD modifying drugs aimed at blocking pathological Abeta aggregation. PMID- 26898941 TI - Refined mapping of autoimmune disease associated genetic variants with gene expression suggests an important role for non-coding RNAs. AB - Genome-wide association and fine-mapping studies in 14 autoimmune diseases (AID) have implicated more than 250 loci in one or more of these diseases. As more than 90% of AID-associated SNPs are intergenic or intronic, pinpointing the causal genes is challenging. We performed a systematic analysis to link 460 SNPs that are associated with 14 AID to causal genes using transcriptomic data from 629 blood samples. We were able to link 71 (39%) of the AID-SNPs to two or more nearby genes, providing evidence that for part of the AID loci multiple causal genes exist. While 54 of the AID loci are shared by one or more AID, 17% of them do not share candidate causal genes. In addition to finding novel genes such as ULK3, we also implicate novel disease mechanisms and pathways like autophagy in celiac disease pathogenesis. Furthermore, 42 of the AID SNPs specifically affected the expression of 53 non-coding RNA genes. To further understand how the non-coding genome contributes to AID, the SNPs were linked to functional regulatory elements, which suggest a model where AID genes are regulated by network of chromatin looping/non-coding RNAs interactions. The looping model also explains how a causal candidate gene is not necessarily the gene closest to the AID SNP, which was the case in nearly 50% of cases. PMID- 26898947 TI - Learning to trust: trust and attachment in early psychosis. AB - BACKGROUND: Distrust and social dysfunction are characteristic in psychosis and may arise from attachment insecurity, which is elevated in the disorder. The relationship between trust and attachment in the early stages of psychosis is unknown, yet could help to understand interpersonal difficulties and disease progression. This study aimed to investigate whether trust is reduced in patients with early psychosis and whether this is accounted for by attachment avoidance and attachment anxiety. METHOD: We used two trust games with a cooperative and unfair partner in a sample of 39 adolescents with early psychosis and 100 healthy controls. RESULTS: Patients had higher levels of attachment anxiety, but the groups did not differ in attachment avoidance. Basic trust was lower in patients than controls, as indicated by lower initial investments. During cooperation patients increased their trust towards levels of controls, i.e. they were able to learn and to override initial suspiciousness. Patients decreased their trust less than controls during unfair interactions. Anxious attachment was associated with higher basic trust and higher trust during unfair interactions and predicted trust independent of group status. Discussion Patients showed decreased basic trust but were able to learn from the trustworthy behaviour of their counterpart. Worries about the acceptance by others and low self-esteem are associated with psychosis and attachment anxiety and may explain behaviour that is focused on conciliation, rather than self-protection. PMID- 26898946 TI - An Examination of Hospital Nurse Staffing and Patient Experience with Care: Differences between Cross-Sectional and Longitudinal Estimates. AB - OBJECTIVE: To study the association between hospital nurse staffing and Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) scores. DATA SOURCES: State hospital financial and utilization reports, Healthcare Cost and Utilization Project State Inpatient Databases, HCAHPS survey, and American Hospital Association Annual Survey of Hospitals. STUDY DESIGN: Retrospective study using cross-sectional and longitudinal models to estimate the effect of nurse staffing levels and skill mix on seven HCAHPS measures. DATA COLLECTION/EXTRACTION METHODS: Hospital-level data measuring nurse staffing, patient experience, and hospital characteristics from 2009 to 2011 for 341 hospitals (977 hospital years) in California, Maryland, and Nevada. PRINCIPAL FINDINGS: Nurse staffing level (i.e., number of licensed practical nurses and registered nurses per 1,000 inpatient days) was significantly and positively associated with all seven HCAHPS measures in cross-sectional models and three of seven measures in longitudinal models. Nursing skill mix (i.e., percentage of all staff who are registered nurses) was significantly and negatively associated with scores on one measure in cross-sectional models and none in longitudinal models. CONCLUSIONS: After controlling for unobserved hospital characteristics, the positive influences of increased nurse staffing levels and skill mix were relatively small in size and limited to a few measures of patients' inpatient experience. PMID- 26898948 TI - Methylamine irisolidone, a novel compound, increases total ATPase activity and inhibits apoptosis in vivo and in vitro. AB - We propose to further research the protective effect of MMI on myocardium ischemic rat model and H9c2 cells that underwent cell apoptosis induced by hypoxia. We established the myocardium ischemic rat model via the cardiac surgical procedures in vivo and treated the model rats with different concentration of MMI. In vitro, with the pretreatment of MMI for 12 h in the model of Na2S2O4-induced hypoxia injury, the H9c2 cells viability was determined by MTT assay. We found that MMI had significantly improved cardiac function of the myocardial ischemia, and significantly decreased the reactive oxygen species level. The expression of P53, Bcl-2, Bax, and caspase-9 was also induced by MMI. In vitro study revealed a concentration-dependent increase in cell viability associated with MMI pretreatment. Annexin V-FITC and PI staining results showed that MMI had a preventive effect on hypoxia-induced apoptosis in H9c2 cells. MMI also inhibited the mitochondrial membrane potential decrease and increased total ATPase activity during hypoxia in H9c2 cells. In conclusion, MMI can enhance the cardiac function in myocardial ischemic rat and increase cell viability and attenuate the apoptosis in H9c2 cells induced by hypoxia, which was associated with inhibiting MMP decreasion and increasing total ATPase activity. PMID- 26898949 TI - Laparoscopic cholecystectomy and concomitant diseases Effectiveness of the single step treatment. AB - AIM: With the expanded use of laparoscopy, the options for combined surgical procedures have also increased and can be a modality of choice for coexisting pathologies in the abdomen. In our study we evaluate the safety and the efficacy of a number of surgical procedures combined with laparoscopic cholecystectomy and report our results. MATERIAL OF STUDY: We conducted a retrospective study on 19 consecutive patients who underwent laparoscopic cholecystectomy simultaneously with other operations. RESULTS: No conversion to open surgery was necessary. Postoperative complications occurred in three patients. The mean postoperative hospital stay was 3 days (range 2-4) and a few patients required more than 48 hours postoperative hospitalization. The perioperative mortality rate was 0%. DISCUSSION: Concomitant surgical procedures result in longer operating time, but certainly the patient benefits from a single exposure to anesthesia, single hospital stay, and single period of absence from work. CONCLUSIONS: Combining surgeries does not significantly alter the outcome of the procedure, proved to be a safe and feasible and present an interesting alternative to two separate operations. Prospective studies with long-term follow-up are required to better understand the implications of simultaneous operations. KEY WORDS: Laparoscopic combined procedures, Minimally invasive surgery. PMID- 26898950 TI - Sclerosing bone dysplasias: genetic, clinical and radiology update of hereditary and non-hereditary disorders. AB - There is a wide variety of hereditary and non-hereditary bone dysplasias, many with unique radiographic findings. Hereditary bony dysplasias include osteopoikilosis, osteopathia striata, osteopetrosis, progressive diaphyseal dysplasia, hereditary multiple diaphyseal sclerosis and pyknodysostosis. Non hereditary dysplasias include melorheostosis, intramedullary osteosclerosis and overlap syndromes. Although many of these dysplasias are uncommon, radiologists should be familiar with their genetic, clinical and imaging findings to allow for differentiation from acquired causes of bony sclerosis. We present an overview of hereditary and non-hereditary bony dysplasias with focus on the pathogenesis, clinical and radiographic findings of each disorder. PMID- 26898951 TI - Pharmacist prescribing: A scoping review about the views and experiences of patients and the public. AB - BACKGROUND: Policy-makers and health professionals' views about pharmacist prescribing have been well studied, but less is known about the views of the public and patients. OBJECTIVE: To describe from existing literature the views and experiences of patients as well as the views of the public about pharmacist prescribing. METHODS: Sources: Medline, EMBASE, and International Pharmaceutical Abstracts from inception to November 2015; reference lists of included studies. INCLUSION CRITERIA: English-language studies describing the views and experiences of patients and the views of the public about pharmacist prescribing. Two reviewers independently screened titles and abstracts and one reviewer charted data. The University of British Columbia Patient Experience Framework was used to categorize and synthesize findings about patients' experience. Views were described using a descriptive thematic synthesis approach. RESULTS: Out of 2377 unique records, 35 articles were reviewed in full for eligibility. Three studies were excluded because participants were not patients or the public, eight studies were not about prescribing, and four studies were abstracts. Two articles were identified from the bibliographies of included studies. In total, twenty-two studies met inclusion criteria. Fourteen studies were quantitative (63.6%), six were qualitative (27.3%) and two were mixed design (9.1%) studies. Four studies (18.2%) were conducted in Canada (Saskatchewan, Newfoundland and Labrador, Nova Scotia), one (4.5%) in Australia, one (4.5%) in the United States (Washington) and the remaining in the United Kingdom (n = 16, 72.7%). The most commonly explored dimensions of patient experiences were access, interpersonal communication, and patient-reported impacts of care. Patients reported high satisfaction with appointment times, communication with the pharmacist prescriber and the services received. The public supported pharmacist prescribing in limited situations (chronic conditions, minor ailments, repeat medications). The public were concerned about privacy during consultations but patients were less so. Both patients and the public shared concerns regarding lack of adequate resources to ensure safe prescribing by pharmacists (e.g., lack of pharmacists' access to medical records, lack of additional staff support to fulfill prescribing responsibilities). CONCLUSION: Patients' experiences with pharmacist prescribing were generally positive. There were shared concerns between patients and the public about pharmacist prescribing. Opportunities for further research include strategies for building public experience with pharmacist prescribing and methods for addressing concerns identified by patients and the public. PMID- 26898952 TI - Oscillating primary transcripts harbor miRNAs with circadian functions. AB - The roles of miRNAs as important post-transcriptional regulators in the circadian clock have been suggested in several studies. But the search for circadian miRNAs has led to disparate results. Here we demonstrated that at least 57 miRNA primary transcripts are rhythmically transcribed in mouse liver. Most of these transcripts are under the regulation of circadian transcription factors such as BMAL1/CLOCK and REV-ERBalpha/beta. However, the mature miRNAs derived from these transcripts are either not oscillating or oscillating at low amplitudes, which could explain the inconsistency of different circadian miRNA studies. In order to show that these circadian primary transcripts can give rise to miRNAs with circadian functions, we over-expressed one of them, miR-378, in mouse by adenovirus injection. We found a significant over-representation of circadian oscillating genes under-expressed by miR-378 over-expression in liver. In particular, we observed that miR-378 modulates the oscillation amplitudes of Cdkn1a in the control of cell cycle and Por in the regulation of oxidation reduction by forming partnership with different circadian transcription factors. Our study suggests that circadian transcription of miRNA at primary transcript level can be a good indicator for circadian miRNA functions. PMID- 26898954 TI - Metadiscourse markers in biological research articles and journal impact factor: Non-native writers vs. native writers. AB - Metadiscourse markers (MDMs) are lexical resources that writers employ to organize their discourse and state their stance towards the content or the reader. This study investigated the frequency with which interactive and interactional MDMs were employed in biological research articles (RAs). It also explored the possible relationship between the frequency of these markers and Impact Factor (IF) of journals as an index of quality. Moreover, it aimed at finding out the difference(s) between two groups of authors (Iranian and American) in their use of these markers. Forty biological RAs published in years 2008-2011 written by Iranian non-native authors and published in four ISI journals with different IFs and 40 articles with the same characteristics published by American native authors were selected and examined for the use of the markers. The results showed that there was a strong positive correlation between the frequency of MDMs and IF of the journals. Regarding the frequency of MDMs, it was observed that Iranian authors employed interactive and interactional markers slightly more than their American counterparts. These results may provisionally confirm the considerable role of MDMs in enhancing the coherence and organization of articles for possible publication in high-impact journals. (c) 2016 by The International Union of Biochemistry and Molecular Biology, 44(4):349-360, 2016. PMID- 26898953 TI - Natural variation in non-coding regions underlying phenotypic diversity in budding yeast. AB - Linkage mapping studies in model organisms have typically focused their efforts in polymorphisms within coding regions, ignoring those within regulatory regions that may contribute to gene expression variation. In this context, differences in transcript abundance are frequently proposed as a source of phenotypic diversity between individuals, however, until now, little molecular evidence has been provided. Here, we examined Allele Specific Expression (ASE) in six F1 hybrids from Saccharomyces cerevisiae derived from crosses between representative strains of the four main lineages described in yeast. ASE varied between crosses with levels ranging between 28% and 60%. Part of the variation in expression levels could be explained by differences in transcription factors binding to polymorphic cis-regulations and to differences in trans-activation depending on the allelic form of the TF. Analysis on highly expressed alleles on each background suggested ASN1 as a candidate transcript underlying nitrogen consumption differences between two strains. Further promoter allele swap analysis under fermentation conditions confirmed that coding and non-coding regions explained aspartic and glutamic acid consumption differences, likely due to a polymorphism affecting Uga3 binding. Together, we provide a new catalogue of variants to bridge the gap between genotype and phenotype. PMID- 26898956 TI - Simultaneous detection of three lily-infecting viruses using a multiplex Luminex bead array. AB - A Luminex bead array was applied to detect multiple-virus coinfection in lily plants exhibiting typical symptoms, and the efficiency of this detection system was assessed. Specific primer sets for the simultaneous detection of 4 targets in virus-infected lily plants were constructed and used for reverse transcription (RT)-polymerase chain reaction (PCR), and specific probes were used for Luminex based assay. Each of the 4 targets was amplified, and the amplicons were used for Luminex bead array experiments. A Luminex bead array analysis of lily-infecting viruses was performed using the quadruplex RT-PCR products followed by hybridization between the biotinylated targets and anti-tagged microsphere beads. The hybridization products produced fluorescence signals that were detected by the Luminex system. Signal strengths were analyzed by their median fluorescence intensity (MFI) values. Detection of the different target elements was found to be very specific to the corresponding viruses in lilies, and coinfection with multiple viruses was specifically detected via the MFI signals. Therefore, the use of a Luminex bead array for the detection of co-infected multiple viruses in lily plants can be an improved system for screening and analyzing multiple-virus infection. PMID- 26898955 TI - Association of Acculturation and Health Literacy with Prevalent Dysglycemia and Diabetes Control Among Latinos in the Boston Area Community Health (BACH) Survey. AB - This study assessed the effect of acculturation on type 2 diabetes and whether health literacy may mediate this association. The Boston Area Community Health cohort is a multi-stage stratified random sample of adults from Boston including 744 Latinos. We defined dysglycemia as a HbA1c >=5.7 %. Multivariable analyses examined the associations between acculturation and health literacy adjusting for demographic and clinical variables. Similar analyses were performed among participants with HbA1c >=7.0 % to assess the association between acculturation and diabetes control. Among an insured primarily foreign born Spanish speaking Latino population, with a long residence period in the US and good healthcare utilization, higher levels of acculturation were not associated with dysglycemia. Lower levels of acculturation were associated with worse diabetes control. Health literacy level did not modify these associations. Elucidating the components of heterogeneity among Latinos will be essential for understanding the influence of acculturation on diabetes. PMID- 26898957 TI - A novel dual luciferase assay for the simultaneous monitoring of HIV infection and cell viability. AB - Human immunodeficiency virus type 1 (HIV-1) reporter cell lines are critical tools for drug development. However, one disadvantage of HIV-1 reporter cell lines is that reductions in reporter gene activity need to be normalized to cytotoxicity, i.e., live cell numbers. Here, we developed a dual luciferase assay based on a R. reniformis luciferase (hRLuc)-expressing R5-type HIV-1 (NLAD8 hRLuc) and a CEM cell line expressing CCR5 and firefly luciferase (R5CEM-FiLuc). The NLAD8-hRLuc reporter virus was replication competent in peripheral blood mononuclear cells. The level of hRLuc was correlated with p24 antigen levels (p<0.001, R=0.862). The target cell line, R5CEM-FiLuc, stably expressed the firefly luciferase (FiLuc) reporter gene and allowed the simultaneous monitoring of compound cytotoxicity. The dual reporter assay combining a NLAD8-hRLuc virus with R5CEM-FiLuc cells permitted the accurate determination of drug susceptibility for entry, reverse transcriptase, integrase, and protease inhibitors at different multiplicities of infection. This dual reporter assay provides a rapid and direct method for the simultaneous monitoring of HIV infection and cell viability. PMID- 26898959 TI - Practical Rehabilitation and Physical Therapy for the General Equine Practitioner. AB - Physical treatment and rehabilitation play major roles in recovery and maintenance of the equine athlete, and many therapeutic measures are accessible by the veterinarian in general practice. An accurate diagnosis of the condition undergoing treatment is a requirement, and measurable parameters obtained at diagnosis allows for quantification of treatment outcomes. Therapeutic modalities accessible to the general practicing veterinarian are reviewed. Mechanisms of action, indications, and treatment protocols of thermal therapy, therapeutic ultrasound, extracorporeal shock wave, and laser are discussed. Manipulative therapies, including stretching and use of core strengthening exercises and equipment, are outlined. PMID- 26898958 TI - Biased signalling from the glucocorticoid receptor: Renewed opportunity for tailoring glucocorticoid activity. AB - Recent landmark studies applying analytical pharmacology approaches to the glucocorticoid receptor (GR) have demonstrated that different ligands can cause differential activation of distinct GR-regulated genes. Drawing on concepts of signalling bias from the field of G protein-coupled receptor (GPCR) biology, we speculate that ligand-dependent differences in GR signalling can be considered analogous to GPCR biased signalling, and thus can be quantitatively analysed in a similar way. This type of approach opens up the possibility of using rational structure-based drug optimisation strategies to improve the therapeutic selectivity of glucocorticoid drugs to maximise their efficacy and minimise adverse effects. PMID- 26898960 TI - Physiotherapy Assessment for the Equine Athlete. AB - Physiotherapy assessment of the equine athlete is carried out by qualified physiotherapists, who use a functional approach to the assessment of the horse. Observation, clinical reasoning, good palpation skills and implementation of outcome measures are skills used by these professionals in their assessment of the horse. Equine physiotherapists attempt, where possible, to use an evidence based approach to the assessment of the equine athlete. PMID- 26898961 TI - Hyperbaric Oxygen Therapy in Equine Rehabilitation: Putting the Pressure on Disease. AB - There are several beneficial physiologic and therapeutic effects of hyperbaric oxygen therapy (HBOT). The indications list for the use of HBOT in the horse has been developed through extrapolation from a review of human indications and from anecdotal clinical experiences. Hyperbaric therapy is a safe treatment option with very few side effects when administered properly. PMID- 26898962 TI - Principles and Application of Hydrotherapy for Equine Athletes. AB - Hydrotherapy has become a key element within equine rehabilitation protocols and is used to address range of motion, proprioception, strength, neuromotor control, pain, and inflammation. Various forms of hydrotherapy can be tailored to the individual's injury and the expected return to athletic performance. This article describes the mechanisms of action of hydrotherapies and potential use in the clinical management of equine musculoskeletal injuries. PMID- 26898963 TI - Kinesio Taping Fundamentals for the Equine Athlete. AB - The Kinesio taping method was developed in Japan for use in humans in 1979. The use of complementary therapies is becoming common in equine athletes and the discovery of Kinesio taping potential brought it into the animal world. Kinesio taping can be used to treat a wide range of clinical conditions, from tendon injuries to neurologic disorders and from muscle contractures to postural insufficiencies. Its use in veterinary medicine is promising, but relies heavily on evidence-based clinical reports. Further scientific research is needed to fully understand the real effectiveness of application. PMID- 26898964 TI - Controlled Exercise in Equine Rehabilitation. AB - Controlled exercise is a fundamental and critical component of any rehabilitation program for the equine athlete. The ideal controlled exercise program is designed to complement the normal tissue reparative process after injury. As a general rule, the program starts with complete rest followed by stall rest and short periods of walking. Over time, the intensity of the controlled exercise is gradually and systemically increased until complete healing has occurred. A well designed, injury-directed, controlled exercise program enhances the healing process. PMID- 26898965 TI - Olanzapine-related repetitive focal seizures with lingual dystonia. AB - Olanzapine-related seizures have rarely been reported despite associated proconvulsant risk factors described in the literature: myoclonic status, increased frequency of seizures, tonic-clonic seizures, as well as fatal status epilepticus. We present a psychiatric patient who developed repetitive focal motor seizures and lingual dystonia when olanzapine was added for psychomotor agitation and aggressiveness. Olanzapine was immediately suspended and the seizures progressively disappeared. A control EEG showed no paroxysmal discharges. Olanzapine shares some pharmacological similarities with clozapine, a neuroleptic with a high risk of dose-dependent seizures. This adverse effect should be taken into account, and olanzapine should be used with caution if concomitant circumstances decrease the seizure threshold. [Published with video sequence online]. PMID- 26898966 TI - Neuropsychiatric symptoms are very common in premanifest and early stage Huntington's Disease. AB - BACKGROUND: Neuropsychiatric symptoms are common features of Huntington's disease (HD). Whereas most studies have focused on cognitive and neuroimaging markers of disease progression, little is known about the prevalence of neuropsychiatric symptoms in premanifest mutation carriers far-from and close-to disease onset. METHODS: We obtained neurological, cognitive and behavioral data from 230 participants classified as premanifest far-from (preHD-A) and close-to (preHD-B) motor-based disease onset, early-symptomatic (early-HD), and healthy controls. Frequency and severity of neuropsychiatric symptoms were assessed with the short Problem Behaviors Assessment for HD (PBA-s). The odds-ratio (OR) to present symptoms in the clinical range was calculated using the control group as reference. Logistic regression analysis was used to explore relationships between neuropsychiatric symptoms and medication use. RESULTS: Prevalence of depression was similar in all groups. Apathy was already present in 32% of preHD-A increasing to 62% of early-HD patients. The probability of presenting apathetic symptoms was 15-88 times higher in preHD-A and preHD-B respectively than in healthy controls. Irritability and executive dysfunction were present in both preHD-B and early-HD. CONCLUSION: Neuropsychiatric symptoms are highly prevalent in HD, already in the premanifest stage, with increasing prevalence of irritability, apathy and executive dysfunction closer to onset. Compared to controls, HD mutation carriers have the highest probability to develop apathy, with an increasing prevalence along disease stages. Our findings confirm the high prevalence of neuropsychiatric symptoms in HD, already many years before the onset of motor symptoms, with apathy as an early manifestation and core neuropsychiatric feature of the disease. PMID- 26898968 TI - Sudden cardiac death in athletes. PMID- 26898967 TI - The grain Hardness locus characterized in a diverse wheat panel (Triticum aestivum L.) adapted to the central part of the Fertile Crescent: genetic diversity, haplotype structure, and phylogeny. AB - Wheat belongs to the most important crops domesticated in the Fertile Crescent. In this region, fortunately, locally adapted wheat landraces are still present in farmers' fields. This material might be of immense value for future breeding programs. However, especially wheat germplasm adapted to the central part of the Fertile Crescent has been poorly characterized for allelic variation at key loci of agricultural importance. Grain hardness is an important trait influencing milling and baking quality of wheat. This trait is mainly determined by three tightly linked genes, namely, Puroindoline a (Pina), Puroindoline b (Pinb), and Grain softness protein-1 (Gsp-1), at the Hardness (Ha-D) locus on chromosome 5DS. To investigate genetic diversity and haplotype structure, we resequenced 96 diverse wheat lines at Pina-D1, Pinb-D1, Gsp-A1, Gsp-B1, and Gsp-D1. Three types of null alleles were identified using diagnostic primers: the first type was a multiple deletion of Pina-D1, Pinb-D1, and Gsp-D1 (Pina-D1k), the second was a Pina-D1 deletion (Pina-D1b); and the third type was a deletion of Gsp-D1, representing a novel null allele designated here as Gsp-D1k. Sequence analysis resulted in four allelic variants at Pinb-D1 and five at Gsp-A1, among them Gsp A1-V was novel. Pina-D1, Gsp-B1 and Gsp-D1 sequences were monomorphic. Haplotype and phylogenetic analysis suggested that (1) bread wheat inherited its 5DS telomeric region probably from wild diploid Ae. tauschii subsp. tauschii found within an area from Transcaucasia to Caspian Iran; and that (2) the Ha-A and Ha-B homoeoloci were most closely related to sequences of wild tetraploid T. dicocco ides. This study provides a good overview of available genetic diversity at Pina D1, Pinb-D1, and Gsp-1, which can be exploited to extend the range of grain texture traits in wheat. PMID- 26898969 TI - Can cardiopulmonary bypass system with blood priming become a new standard in coronary surgery? AB - BACKGROUND: Commonly used cardiopulmonary bypass systems with cardiotomy reservoir, oxygenator, and roller pump require preoperative crystalloid filling. Radical reduction of the filling fluid volume and replacing it with the patient's own blood has a fundamental impact on the outcome. AIM: A comparison of cardiopulmonary bypass filled with the patient's blood, applied in Poland for the first time, and the classical system filled with crystalloids. METHODS: Non randomised trial in which patients undergoing coronary artery bypass grafting were divided into two groups: first operated on with use of cardiopulmonary bypass system with the patient's own blood priming, and a control group operated on with standard technique. Levels of haemoglobin (HGB), haematocrit (HCT), platelets, leukocytes, creatinine, protein, C-reactive protein, procalcitonin, volume of transfused blood products, postoperative drain output, time to extubation, and consumption of catecholamines were compared. RESULTS: The results of a study comparing the classical system with the blood-filled system (n = 60) showed a significantly smaller decrease in HGB and HCT levels (p = 0.001), resulting in reduction of blood product transfusions by 75% (p = 0.03). The new type of extracorporeal circulation reduced the total postoperative drain output by approximately 28% (p = 0.003). The systemic inflammatory response syndrome (SIRS) was less pronounced and the tissue perfusion was better due to smaller degree of haemodilution leading to better organ and heart protection. The patients required shorter mechanical ventilation times in the perioperative period. CONCLUSIONS: The use of a new system of cardiopulmonary bypass filled with the patient's blood reduces the postoperative decrease in HGB and HCT, the amount of transfused blood products, and total postoperative drain output. It also shortens the time spent on mechanical ventilatory support. PMID- 26898970 TI - Day by day telemetric care of patients treated with cardiac resynchronisation therapy: first Polish experience. AB - BACKGROUND: Due to the recent rapid increase in the number of patients implanted with pacemakers, cardioverter-defibrillators (ICD), and cardiac resynchronisation therapy devices (CRT), conventional monitoring at specialist clinics is becoming increasingly difficult. The development of technology has enabled remote device monitoring with the use of teletransmission systems. AIM: To assess the effectiveness of transmission and the possibility of using telemetric data for further clinical management of patients with heart failure (HF) treated with CRT D. METHODS: The analysis included 305 consecutive patients with chronic HF, New York Heart Association functional classes II-IV, treated with the use of CRT-D by Biotronik or Medtronic in the years 2006-2012. The patients received transmitters, enabling the remote monitoring of the implanted device from the patients' houses. Scheduled reports were automatically sent every month. The triggers for pre-specified emergency alert transmissions were as follows: ventricular tachycardia (VT) or ventricular fibrillation (VF) episodes, CRT-D intervention, ventricular extrasystoles > 110/h, any episode of atrial fibrillation (AF), atrial flutter (AFL) or supraventricular tachycardia, mean heart rate (HR) during, mean 24-h HR, CRT pacing < 95%, Elective Replacement Indicator, or End Of Service and device malfunction. The all-cause mortality of the study population has been assessed at the end of the follow-up period (mean of 20.5 months). RESULTS: Devices manufactured by Biotronik were provided to 71% of the study population, while 29% received devices by Medtronic. In 97.3% of cases, the monitors were wireless, fully automatic, and capable of immediate data transmission whenever a pre-specified alert notification was fulfilled. The analysis of long-term outcomes revealed that all-cause mortality of the whole study population was 13%. The effectiveness of report transmission was 98%. During follow-up a total of 31,198 transmissions were received and analysed, which constituted, on average, 4.9 transmissions per patient per month. Among analyses, 30% were reports generated by scheduled remote follow-ups, and 70% were caused by unscheduled device alerts. Correct functioning of the system was confirmed; the quality of the received data was 100%. In 63.9% of patients, decisions based on the information obtained from telemonitoring reports were made to modify the therapy, refer the patients to cardiology or electrophysiology clinics, or hospitalise them urgently. The most common medical reaction was device reprogramming (46.8%). Pharmacotherapy was modified in 33.7% of patients: beta-blocker dose increase (25.9%), anticoagulant treatment inclusion (15.7%), amiodarone inclusion (1.9%), or digoxin inclusion (4.5%). The remaining medical responses were referring patients for atrioventricular junction ablation (8.1%), VT ablation (2.9%), or AF/AFl ablation (1.6%). CONCLUSIONS: Remote monitoring of implantable devices is feasible, safe, and effective in supervising patients with CRT-D devices. Daily-based remote monitoring of a large population of HF patients allows continuous "triage" of high-risk patients and selection of individuals who require urgent intervention. PMID- 26898971 TI - The impact of multiple stent implantation in the infarct-related artery on one year clinical outcomes of patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention. Data from the Polish NRDES Registry. AB - BACKGROUND AND AIM: We sought to evaluate the impact of multiple stent implantation in the infarct-related artery (IRA) on one-year clinical outcomes of patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). METHODS AND RESULTS: Data on 1741 consecutive patients with STEMI, who underwent immediate PCI with implantation of >= 1 stent, enrolled the National Registry of Drug Eluting Stents (NRDES) were assessed. Patients were stratified based on the number of implanted stents in IRA: 1 vs. >= 2 stents. At the discretion of operators, >= 2 stents in IRA were implanted in 247 (14.2%) patients. The remaining 1494 patients were treated with a single stent. Patients treated with multiple stents were less likely to achieve Thrombolysis In Myocardial Infarction (TIMI) grade 3 flow after primary PCI. Overall mortality at one year was 8.3% in the single stent group and 10.3% in the >= 2 stents group (p = 0.37; adjusted for propensity score p = 0.13). After propensity score matching, patients treated with >= 2 stents were at higher risk of definite or probable stent thrombosis and urgent revascularisation at one year. CONCLUSIONS: In patients with STEMI undergoing primary PCI, a need for implantation of >= 2 stents in IRA carries an increased risk of stent thrombosis and urgent revascularisation at one year. PMID- 26898972 TI - Blood management after total joint arthroplasty in the United States: 19-year trend analysis. AB - BACKGROUND: Recent studies have failed to show reductions in rates of red blood cell (RBC) transfusion after total joint arthroplasty (TJA) in the United States. This study aims to report the 19-year trend analysis of blood use in TJA, to determine predictors of RBC transfusion and association between RBC transfusion and in-hospital mortality after TJA using a nationally representative database. STUDY DESIGN AND METHODS: Nationwide inpatient sample (NIS) data from 1993 to 2011 were used. ICD-9-CM codes were used to identify TJA cases, RBC transfusion, autologous blood transfusion, and/or transfusion from cell salvage. Logistic regression analysis was performed to determine predictors of RBC transfusion and if transfusion increases risk of in-hospital mortality. RESULTS: A total of 2,225,054 TJA cases were identified. Using multivariate analysis, there was an increase in the rate of RBC transfusion over the study period (odds ratio [OR], 1.049; 95% confidence interval [CI], 1.048-1.050; p < 0.001). One-stage bilateral TJA (OR, 3.30; 95% CI, 3.24-3.37; p < 0.001), anemia due to chronic blood loss (OR, 2.69; 95% CI, 2.59-2.74, p < 0.001), deficiency anemia (OR, 2.59; 95% CI, 2.56-2.62; p < 0.001), and Charlson comorbidity index (OR, 1.24; 95% CI, 1.23 1.24; p < 0.001) were independent predictors of allogeneic blood transfusion. Transfusion of autologous blood reduced need for RBC transfusion (OR, 0.84; 95% CI, 0.82-0.85; p < 0.001). RBC transfusion was an independent predictor of in hospital mortality (OR, 1.537; 95% CI, 1.395-1.694; p < 0.001). CONCLUSION: An increase in the rate of RBC use after TJA and the association between allogeneic blood transfusion and mortality are worrisome. Implementing more effective blood conservation strategies is recommended. PMID- 26898974 TI - Discussion. PMID- 26898973 TI - Bioanalytical method development for quantification of ulifloxacin, fenbufen and felbinac in rat plasma by solid-phase extraction (SPE) and HPLC with PDA detection. AB - A procedure based on solid-phase extraction (SPE) followed by high performance liquid chromatography (HPLC) with PDA detection has been developed for the analysis of multiple drugs in rat plasma. The analytes evaluated were ulifloxacin, fenbufen and felbinac. Eight different solid phase extraction cartridges were tested to evaluate their applicability for the isolation of drugs from rat plasma. Comparison were recovery of different drugs and reproducibility. The samples were analyzed by HPLC using a Kinetex C18 EVO column and acetonitrile 10mM ammonium acetate-methanol as the mobile phase under gradient elution conditions. SPE combined with HPLC-PDA allowed the determination of drugs over a linear range of 0.05-15 MUg/mL for ulifloxacin while 0.5-50 MUg/mL for felbinac and fenbufen, with limit of detection at 0.05 for ulifloxacin and 0.5 for felbinac and fenbufen. Bond Elut Plexa sorbent was found to provide the most effective clean-up, removing the greatest amount of interfering substance and simultaneously ensuring analyte recoveries higher than 93.54% with relative standard deviation (RSD) <10%. The method was applied with good accuracy and precision in the determination of ulifloxacin, fenbufen and felbinac in rat plasma obtained from rats treated with selected drugs. This method permits its application to pharmacokinetic and pharmacodynamic studies of these analytes and will facilitate detailed investigations on the interactions between new fluoroquinolones and fenbufen. PMID- 26898976 TI - Discussion. PMID- 26898977 TI - Discussion. PMID- 26898975 TI - The rise of new technologies for aortic valve stenosis: A comparison of sutureless and transcatheter aortic valve implantation. AB - OBJECTIVE: Transcatheter aortic valve implantation (TAVI) and sutureless aortic valve replacement (SU-AVR) are suitable alternatives to conventional surgery. The aim of this study is to compare early outcomes of patients undergoing TAVI and SU AVR. METHODS: Data were analyzed on patients who underwent TAVI and patients who underwent SU-AVR. Two matched cohorts (TAVI vs SU-AVR) were created using propensity scores; all analyses were repeated for transapical TAVI and transfemoral TAVI, separately. Outcomes were defined according to Valve Academic Research Consortium-2 criteria. RESULTS: A total of 2177 patients were included in the analysis: 1885 (86.6%) treated with TAVI; 292 (13.4%) treated with SU-AVR. Mortality in unmatched TAVI and SU-AVR patients was 7.1% and 2.1%, respectively, at 30 days, and 12.9% and 4.6%, respectively, at 1 year. No differences were found in 30-day mortality in the 214 matched patient pairs (3.7% vs 2.3%; P = .4), but patients treated with TAVI showed a lower incidence of device success (85.9% vs 98.6%; P < .001) and pacemaker implantation (2.8% vs 9.4%; P = .005), and a higher incidence of any paravalvular leakage (PVL). CONCLUSIONS: SU-AVR is associated with better device success and a lower incidence of PVL, compared with TAVI. Nevertheless, patients treated with SU-AVR were more likely to receive a permanent pacemaker. SU-AVR and TAVI provide good results in patients who have severe symptomatic aortic valve stenosis. Given the multiple therapeutic options available, patients may receive the treatment that is most appropriate for their clinical and anatomical characteristics. PMID- 26898978 TI - Transplantation of "high-risk" donor hearts: Implications for infection. AB - BACKGROUND: Heart transplantation is the gold-standard treatment for end-stage heart failure. Short- and long-term outcomes have been excellent, but the shortage of organs persists. The number of potential recipients who die while awaiting orthotopic heart transplantation increases yearly. In 2004, the label "high-risk donor" (HRD) was applied, by the United Network for Organ Sharing (UNOS), to any organ donor who met the Centers for Disease Control (CDC) criteria for behavior that put them at high risk of infection. Despite organ shortages, grafts from HRD CDCs are often declined, because of concerns regarding infection. We undertook this study to analyze our extensive experience with orthotopic heart transplantation of grafts from HRD CDCs, and to determine the short- and long term outcomes associated with recipients of hearts from HRD CDCs, particularly transmission of infection. METHODS: We performed 367 heart transplantations at our center from September 2008 to September 2014, a timeframe during which the HRD CDC labeling had been implemented. Of the total number of orthotopic heart transplantations performed, 55 patients (15%) received organs from HRD CDCs that had known negative serology for human immunodeficiency virus (HIV), hepatitis B, and hepatitis C. We reviewed demographic, perioperative, and short- and long-term outcomes. The recipients of grafts from HRD CDCs were followed closely, with 3- and 12-month surveillance laboratory testing of viral load for HIV, for hepatitis B, and for hepatitis C core- and surface-antigen serology. RESULTS: All 55 patients (72.7% were men) underwent a successful transplantation procedure. One patient was excluded from follow-up analysis because he was re-transplanted within 4 days owing to the posttransplant finding of metastatic lung adenocarcinoma within the donor. Primary etiology of heart failure was ischemic in 18 of the patients. The most common blood type was O positive, in 20 patients (37.1%), followed by A positive, in 19 patients (35.2%). A total of 19 (35.2%) patients were supported with a mechanical assist device before the transplantation. The average allograft ischemic time was 173 +/- 96 minutes. The median length of hospital stay was 19.5 days. A low incidence was observed of the postoperative complications of stroke (1.9%), dialysis (3.9%), and complete heart block (3.9%). Kaplan-Meier analysis demonstrated excellent survival, both short term (1 year; 94%) and long-term (3 years; 80%). Allograft function was excellent at time of discharge with a left ejection fraction of 67.8% +/- 7.3%. Only one patient (1.9%) was noted to have hepatitis C seroconversion at 105 days after receiving the transplant. After antiviral treatment, the patient has had undetectable viral loads to date. All other patients had undetectable plasma viral loads of HIV, hepatitis C, and hepatitis B, determined using rigorous testing. CONCLUSIONS: We present the only single-center series on recipients of heart transplants from HRD CDCs. This potential source of suitable donor organs is shown to lead to excellent survival, without an increased incidence of perioperative or postoperative complications. Furthermore, the risk of transmission of infection from donors in this subgroup seems to be minimal. PMID- 26898979 TI - Outcomes of 3309 thoracoabdominal aortic aneurysm repairs. AB - OBJECTIVE: Since the pioneering era of E. Stanley Crawford, our multimodal strategy for thoracoabdominal aortic aneurysm repair has evolved. We describe our approximately 3-decade single-practice experience regarding 3309 thoracoabdominal aortic aneurysm repairs and identify predictors of early death and other adverse postoperative outcomes. METHODS: We analyzed retrospective (1986-2006) and prospective data (2006-2014) obtained from patients (2043 male; median age, 67 [59-73] years) who underwent 914 Crawford extent I, 1066 extent II, 660 extent III, and 669 extent IV thoracoabdominal aortic aneurysm repairs, of which 723 (21.8%) were urgent or emergency. Repairs were performed to treat degenerative aneurysm (64.2%) or aortic dissection (35.8%). The outcomes examined included operative death (ie, 30-day or in-hospital death) and permanent stroke, paraplegia, paraparesis, and renal failure necessitating dialysis, as well as adverse event, a composite of these outcomes. RESULTS: There were 249 operative deaths (7.5%). Permanent paraplegia and paraparesis occurred after 97 (2.9%) and 81 (2.4%) repairs, respectively. Of 189 patients (5.7%) with permanent renal failure, 107 died in the hospital. Permanent stroke was relatively uncommon (n = 74; 2.2%). The rate of the composite adverse event (n = 478; 14.4%) was highest after extent II repair (n = 203; 19.0%) and lowest after extent IV repair (n = 67; 10.2%; P < .0001). Estimated postoperative survival was 83.5% +/- 0.7% at 1 year, 63.6% +/- 0.9% at 5 years, 36.8% +/- 1.0% at 10 years, and 18.3% +/- 0.9% at 15 years. CONCLUSIONS: Repairing thoracoabdominal aortic aneurysms poses substantial risks, particularly when the entire thoracoabdominal aorta (extent II) is replaced. Nonetheless, our data suggest that thoracoabdominal aortic aneurysm repair, when performed at an experienced center, can produce respectable outcomes. PMID- 26898981 TI - Adjuvant properties of water extractable arabinoxylans with different structural features from wheat flour against model antigen ovalbumin. AB - Despite the numerous benefits of AX on the immune system and gut bacteria, the potential adjuvant activity of WEAX on immune responses has not been adequately investigated. In the present study, three kinds of WEAX with different structural features were obtained and their adjuvant potential on the specific cellular and humoral immune responses in ovalbumin (OVA) immunized mice were assessed. Our data demonstrated that WEAX had potent effects on innate and acquired immune responses through up-regulating the NK cell activation and promoting the Th2 type immune response. Furthermore, this study also elucidated the possible relationship between the adjuvant activity of WEAX and the structure. Compared with the other characteristics of the WEAX, we found that the immunomodulatory activity may be related to their content of ferulic acid, and not to the molecular weight. PMID- 26898982 TI - Knowledge, illness perceptions and stated clinical practice behaviour in management of gout: a mixed methods study in general practice. AB - The objective of the present study is to explore knowledge, illness perceptions and stated practice behaviour in relation to gout in primary care. This is a mixed methods study among 32 general practitioners (GPs). The quantitative assessment included the Gout Knowledge Questionnaire (GKQ; range 0-10; better) and Brief Illness Perceptions Questionnaire (BIPQ; nine items, range 0-10; stronger). Structured individual interviews obtained further qualitative insight into knowledge and perceptions, in the context of daily practice. Among 32 GPs, 18 (56.3 %) were male, mean age 44.4 years (SD 9.6) and mean working experience 17.1 years (SD 9.7). Median score [interquartile ranges (IQR)] on the GKQ was 7.8 [6.7-8.9] and 9.0 [8.0-10.0], when presented as open or multiple-choice questions, respectively. The BIPQ (median; [IQR]) revealed that gout was seen as a chronic disease (8.0; [7.0-9.0]), affecting life and emotions moderately (6.5; [5.0-7.0]), having many severe symptoms (8.0; [7.0-9.0]) and in which treatment could be very helpful (8.0; [7.0-9.0]). Further interviews revealed large variation in specific aspects of knowledge and about gaps concerning indications for uric acid-lowering therapy (UALT), duration of UALT, target serum uric acid (sUA) level or duration of prophylactic treatment. Finally, patients' adherence was not checked systematically. Specific knowledge gaps and discrepancies between perceptions and stated practice behaviour were identified, which might hamper effective management of this well-treatable disease. Improving evidence on the rationale and effectiveness of treatment targets and adherence interventions, tailoring guidelines to general practice and intensification of implementation of guidelines in primary health care seem to be needed. PMID- 26898983 TI - Serum dehydroepiandrosterone sulfate and osteoarthritis in older people: the Pro.V.A. study. AB - Although osteoarthritis (OA) and low levels of dehydroepiandrosterone sulfate (DHEAS) are common in the elderly, no studies on human beings are available concerning the possible relationship between them. We aimed to examine the relationship between DHEAS levels and any presence of OA in a cohort of community dwelling older subjects. This study was part of the Progetto Veneto Anziani (Pro.V.A.), an Italian population-based cohort study on people over 65 years old. In this cross-sectional work, we considered 2050 individuals with a mean age of 74.2 +/- 7.1 years (818 M and 1232 F), and with a complete set of information on OA and DHEAS levels. OA was defined using a standardized algorithm investigating disease history, medical records, symptoms, use of analgesic drugs for OA, and physical examination of the hand, hip, and knee. DHEAS levels were classified using gender-specific tertiles. OA at the three sites investigated was significantly more common in women than in men, and in individuals with lower serum DHEAS concentrations. On logistic regression analysis, taking those in the highest DHEAS tertile for reference and adjusting for potential confounders, subjects in the lowest tertile had significantly higher odds of OA involving the hand (men: OR = 1.49; 95 % CI 1.31-1.70, women: 1.28; 95 % CI 1.16-1.41), hip (men: 1.55; 95 % CI 1.33-1.81; women: 1.17; 95 % CI 1.06-1.30), and knee (men: 1.54; 95 % CI 1.35-1.76; women: 1.31 95 % CI 1.19-1.45). Similar findings emerged for individuals in the intermediate DHEAS tertile. Low DHEAS levels are associated with OA, irrespective of site and gender. PMID- 26898984 TI - Diagnosis of carpal tunnel syndrome assessed using high-frequency ultrasonography: cross-section areas of 8-site median nerve. AB - This study aimed to determine the most suitable site for diagnosis of carpal tunnel syndrome (CTS) by examining an 8-site measurement of the median nerve's cross-sectional area (CSA). A total of 36 wrists of 26 patients with nerve conduction study (NCS) proven CTS, along with 34 wrists of 23 controls whose age and gender were matched with the patients, were evaluated with ultrasonography. The CSAs of the median nerve at eight predetermined sites including at the sites of 3, 2, and 1 cm proximal to the wrist crease, wrist crease, as well as at the sites of 1, 2, 3. and 4 cm distal to the wrist crease were obtained. The correlation between CSA and NCS severity, and duration of clinical CTS symptoms was analyzed. Receiver operating characteristic (ROC) curves was applied to determine the optimum cut-off point and to evaluate the diagnostic sensitivity and specificity of sonographic measurements. The CSAs of the median nerves at the eight sites were significantly higher in the CTS subjects, relative to the controls. Moreover, anatomical variation of the median nerve was found in the CTS group. ROC results indicated the areas under curve (AUC) at the site of 4 cm distal to the wrist crease were the largest with 0.874 cm(2), and an optimal cut off value of 0.095 yielded a sensitivity of 88.9 % and a specificity of 76.5 %. The CSAs of "CTS-wrists" positively correlated with NCS severities and the CTS symptoms duration. Using 8-site CSAs measurement of the median nerve from inlet to outlet has positive correlations with NCS severity and duration of CTS symptoms. PMID- 26898985 TI - Coping mediates the influence of personality on life satisfaction in patients with rheumatic diseases. AB - A rheumatic disease can severely impair a person's quality of life. The degree of impairment, however, is not closely related to objective indicators of disease severity. This study investigated the influence and the interplay of core psychological factors, i.e., personality and coping, on life satisfaction in patients with rheumatic diseases. Particularly, it was tested whether coping mediates the effects of personality on life satisfaction. In a cross-sectional design, 158 patients diagnosed with a rheumatic disease completed questionnaires assessing the Big 5 personality traits (BFI-10), several disease-related coping strategies (EFK) and life satisfaction (HSWBS). Data were analyzed using a complex multiple mediation analysis with the Big 5 personality traits as predictors, coping strategies as mediators and life satisfaction as outcome. All personality traits and seven of the nine coping strategies were associated with life satisfaction (rs > |0.16|, ps <= 0.05). The mediation analysis revealed that personality traits had no direct, but rather indirect effects on life satisfaction through coping. Neuroticism had a negative indirect effect on life satisfaction through less active problem solving and more depressive coping (indirect effects > -0.03, ps < 0.05). Extraversion, agreeableness, and conscientiousness had positive indirect effects on life satisfaction through more active problem solving, less depressive coping and/or a more active search for social support (indirect effects > 0.06, ps < 0.05). Personality and coping play a role in adjustment to rheumatic diseases. The interplay of these variables should be considered in psychological interventions for patients with rheumatic diseases. PMID- 26898986 TI - Screening for hepatocellular carcinoma in high-risk populations. AB - Screening for hepatocellular carcinoma (HCC) should be implemented in the high risk population. High-risk population includes patients with cirrhosis of any etiology, patients with chronic hepatitis B virus with or without cirrhosis, and patients with chronic hepatitis C virus with cirrhosis. A randomized controlled trial of over 18,000 high-risk individuals demonstrated that biannual screening reduced HCC-related mortality by 37%. The screening test of choice is ultrasound imaging with an interval of 6 months. PMID- 26898980 TI - Targeting Hsp70: A possible therapy for cancer. AB - In all organisms, heat-shock proteins (HSPs) provide an ancient defense system. These proteins act as molecular chaperones by assisting proper folding and refolding of misfolded proteins and aid in the elimination of old and damaged cells. HSPs include Hsp100, Hsp90, Hsp70, Hsp40, and small HSPs. Through its substrate-binding domains, Hsp70 interacts with wide spectrum of molecules, ranging from unfolded to natively folded and aggregated proteins, and provides cytoprotective role against various cellular stresses. Under pathophysiological conditions, the high expression of Hsp70 allows cells to survive with lethal injuries. Increased Hsp70, by interacting at several points on apoptotic signaling pathways, leads to inhibition of apoptosis. Elevated expression of Hsp70 in cancer cells may be responsible for tumorigenesis and for tumor progression by providing resistance to chemotherapy. In contrast, inhibition or knockdown of Hsp70 reduces the size of tumors and can cause their complete regression. Moreover, extracellular Hsp70 acts as an immunogen that participates in cross presentation of MHC-I molecules. The goals of this review are to examine the roles of Hsp70 in cancer and to present strategies targeting Hsp70 in the development of cancer therapeutics. PMID- 26898988 TI - Misperception of tiredness in young adults with insomnia. AB - People with insomnia often exhibit interpretive biases to cues associated with their condition. This study examined whether individuals with insomnia display an interpretive bias, such that they misperceive facial attributes of tiredness in a disorder-consistent manner. The efficacy of providing feedback related to the accuracy of participants' perception on later judgements of tiredness was further examined. Forty participants, 20 with DSM-5-defined insomnia disorder and 20 normal-sleepers, participated. The perception of one's own facial appearance of tiredness was assessed twice over two consecutive days using a visual task whereby participants indicated when a morphing image of their face represented their current level of tiredness. Visual and verbal feedback, related to participants' degree of misperception, was provided on completion of Day 1 testing. Overall, individuals with insomnia perceived their own face as significantly more tired than a baseline neutral photograph was, whereas normal sleepers perceived themselves as appearing more alert. This pattern of results was only apparent on Day 1. Although no group * day interaction was established, mean scores suggest an improvement in perception on Day 2 amongst individuals with insomnia only. These findings suggest that individuals with insomnia exhibit a misperception of their facial attributes of tiredness, interpreting them in a disorder-consistent manner. This finding adds to the body of literature on cognitive models of insomnia, demonstrating more general cognitive biases in the disorder. Further, the results provide suggestive evidence that this misperception may be reformed. PMID- 26898990 TI - Synchronous MRI of muscle motion induced by electrical stimulation. AB - PURPOSE: Assessing the functionality of muscle fibers is essential to monitor both pathological and physiological processes. Here, we present a new method for accurate, quantitative measurement of muscle contraction with magnetic resonance imaging (MRI) using an electrical muscle stimulator (EMS), hence allowing the direct assessment of muscle kinematics. METHODS: A commercially available EMS device was used to induce involuntary periodic muscle contraction of the vastus lateralis muscle (VL) synchronized with high-temporal-resolution cine phase contrast MRI acquisition at 3T. The proposed method was evaluated in ten male volunteers at varying levels of stimulation (10-18 mA) and maximum velocity, strain, and strain rate were calculated offline. RESULTS: Artifact-free velocity, strain and strain rate maps were produced and were consistent across the volunteers. Quantitatively, all parameters varied significantly at different levels of stimulation, in an approximately power-law dependence on the stimulation current. At 18 mA maximum contraction speeds at the beginning of the contraction were 4.28 +/- 2.64 cm/s; principal strain was 0.30 +/- 0.12; and positive in-plane strain rate was 0.25 +/- 0.14 s-1 . CONCLUSION: MRI of EMS controlled involuntary muscle contraction is feasible and allows offline calculation of velocity, strain and strain rate maps, which appear to depend significantly on the stimulation current used. Magn Reson Med 77:664-672, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 26898989 TI - The aspirin-induced long non-coding RNA OLA1P2 blocks phosphorylated STAT3 homodimer formation. AB - BACKGROUND: Although the chemopreventive effects of aspirin have been extensively investigated, the roles of many cell components, such as long non-coding RNAs, in these effects are still not completely understood. RESULTS: We identify an aspirin-induced upregulated lncRNA, OLA1P2, in human colorectal cancer. Aspirin induces demethylation of the FOXD3 promoter and promotes expression of the FOXD3 gene. Subsequently, upregulated FOXD3 protein transcriptionally activates lncRNA OLA1P2 expression. OLA1P2 upregulation markedly affects STAT3 signaling pathway activity by inhibiting the nuclear import of phosphorylated STAT3. The phosphorylation of tyrosine-705 of STAT3 is the first step in OLA1P2 binding, and the formation of phosphorylated STAT3 homodimers is subsequently blocked. OLA1P2 interacts directly with STAT3 due to OLA1P2 sharing the same conservative STAT3 transcription response element as STAT3 targets. Regular use of aspirin dramatically decreases the number of metastatic nodules of cancer cells in immunodeficient mouse lungs, and OLA1P2 silencing markedly weakens the anti metastatic activity of aspirin in the lungs. Additionally, low OLA1P2 levels are associated with malignant transformation and lower overall survival in cancers. CONCLUSIONS: The present study finds that the aspirin-FOXD3-OLA1P2-STAT3 axis exhibits exciting anticancer effects and provides new insights into the chemopreventive mechanisms underlying aspirin use. PMID- 26898992 TI - Synthesis of quaternary aryl phosphonium salts: photoredox-mediated phosphine arylation. AB - We report a synthesis method for the construction of quaternary aryl phoshonium salts at ambient temperature. The regiospecific reaction involves the coupling of phosphines with aryl radicals derived from diaryliodonium salts under photoredox conditions. PMID- 26898991 TI - Fish condition factor, peroxisome proliferator activated receptors and biotransformation responses in Sarotherodon melanotheron from a contaminated freshwater dam (Awba Dam) in Ibadan, Nigeria. AB - The relationship between condition factor (CF), peroxisome proliferator-activated receptors (PPARs), phase 1 biotransformation (CYP1A isoforms) and contaminant burden has been studied in Sarotherodon melanotheron from a contaminated tropical freshwater dam (Awba Dam) and compared to a reference site (Modete Dam) in Southwest, Nigeria. A total of 89 fish (57 males and 32 females) was collected from Awba Dam and 95 fish (48 males and 47 females) from the reference site. In general, fish sampled from Awba Dam were bigger than reference site. Sediment samples were also collected from both sites for contaminant analysis. Expression of ppar and cyp1 isoforms was analyzed using validated real-time PCR, while CYP1A and PPAR protein levels were analyzed using immunochemical method with specific antibodies. CYP-mediated catalytic responses (EROD, MROD and BROD) were performed by biochemical methods. We observed significant increases in ppar and cyp1 isoforms mRNA in both male and female fish from Awba Dam, compared to the reference site. Catalytic activities of EROD, MROD and BROD paralleled cyp1 transcript levels. Sex-related differences in PPAR and CYP1A protein levels were also observed, showing higher CYP1A proteins in males, compared with females, and higher PPAR proteins in females compared with males. Principal component analysis (PCA) biplot showed positive relationships between biological responses (ppar isoforms), condition factor (CF) and sediment PCBs, PAHs, OCPs and heavy metal concentrations. The present study shows that S. melanotheron inhabiting Awba Dam are severely affected by different classes of environmental contaminants that target metabolic processes (PPAR) and biotransformation pathways (CYP1A) in male and female fish, compared to a reference site. Interestingly, fish from Awba Dam were exhibiting good growth (evidence by high CF values) that paralleled increases in the transcriptional activation of ppar and cyp1 isoforms, despite the high contaminant burdens, suggesting a possible contaminant-induced obesogenic effects. PMID- 26898993 TI - An adaptive quantum mechanics/molecular mechanics method for the infrared spectrum of water: incorporation of the quantum effect between solute and solvent. AB - Quantum effects in solute-solvent interactions, such as the many-body effect and the dipole-induced dipole, are known to be critical factors influencing the infrared spectra of species in the liquid phase. For accurate spectrum evaluation, the surrounding solvent molecules, in addition to the solute of interest, should be treated using a quantum mechanical method. However, conventional quantum mechanics/molecular mechanics (QM/MM) methods cannot handle free QM solvent molecules during molecular dynamics (MD) simulation because of the diffusion problem. To deal with this problem, we have previously proposed an adaptive QM/MM "size-consistent multipartitioning (SCMP) method". In the present study, as the first application of the SCMP method, we demonstrate the reproduction of the infrared spectrum of liquid-phase water, and evaluate the quantum effect in comparison with conventional QM/MM simulations. PMID- 26898995 TI - Visual cues of motion that trigger animacy perception at birth: the case of self propulsion. AB - Self-propelled motion is a powerful cue that conveys information that an object is animate. In this case, animate refers to an entity's capacity to initiate motion without an applied external force. Sensitivity to this motion cue is present in infants that are a few months old, but whether this sensitivity is experience-dependent or is already present at birth is unknown. Here, we tested newborns to examine whether predispositions to process self-produced motion cues underlying animacy perception were present soon after birth. We systematically manipulated the onset of motion by self-propulsion (Experiment 1) and the change in trajectory direction in the presence or absence of direct contact with an external object (Experiments 2 and 3) to investigate how these motion cues determine preference in newborns. Overall, data demonstrated that, at least at birth, the self-propelled onset of motion is a crucial visual cue that allowed newborns to differentiate between self- and non-self-propelled objects (Experiment 1) because when this cue was removed, newborns did not manifest any visual preference (Experiment 2), even if they were able to discriminate between the stimuli (Experiment 3). To our knowledge, this is the first study aimed at identifying sensitivity in human newborns to the most basic and rudimentary motion cues that reliably trigger perceptions of animacy in adults. Our findings are compatible with the hypothesis of the existence of inborn predispositions to visual cues of motion that trigger animacy perception in adults. PMID- 26898996 TI - Electromagnetic susceptibility anisotropy and its importance for paramagnetic NMR and optical spectroscopy in lanthanide coordination chemistry. AB - The importance of the directional dependence of magnetic susceptibility in magnetic resonance and of electric susceptibility in the optical spectroscopy of lanthanide coordination complexes is assessed. A body of more reliable shift, relaxation and optical emission data is emerging for well-defined isostructural series of complexes, allowing detailed comparative analyses to be undertaken. Such work is highlighting the limitations of the current NMR shift and relaxation theories, as well as emphasising the absence of a compelling theoretical framework to explain optical emission phenomena. PMID- 26898997 TI - [Clinical four-character, journal four-character, and academic development]. PMID- 26898998 TI - [Chinese expert consensus on the diagnosis and tretment of recurrent spontaneous abortion]. PMID- 26898994 TI - Immunoprotective responses of T helper type 1 stimulatory protein-S-adenosyl-L homocysteine hydrolase against experimental visceral leishmaniasis. AB - It is well known that a patient in clinical remission of visceral leishmaniasis (VL) remains immune to reinfection, which provides a rationale for the feasibility of a vaccine against this deadly disease. In earlier studies, observation of significant cellular responses in treated Leishmania patients as well as in hamsters against leishmanial antigens from different fractions led to its further proteomic characterization, wherein S-adenosyl-L-homocysteine hydrolase (AdoHcy) was identified as a helper type 1 (Th1) stimulatory protein. The present study includes immunological characterization of this protein, its cellular responses [lymphoproliferation, nitric oxide (NO) production and cytokine responses] in treated Leishmania-infected hamsters and patients as well as prophylactic efficacy against Leishmania challenge in hamsters and the immune responses generated thereof. Significantly higher cellular responses were noticed against recombinant L. donovani S-adenosyl-L-homocysteine hydrolase (rLdAdoHcy) compared to soluble L. donovani antigen in treated samples. Moreover, stimulation of peripheral blood mononuclear cells with rLdAdoHcy up-regulated the levels of interferon (IFN)-gamma, interleukin (IL)-12 and down-regulated IL-10. Furthermore, vaccination with rLdAdoHcy generated perceptible delayed-type hypersensitivity response and exerted considerably good prophylactic efficacy (~70% inhibition) against L. donovani challenge. The efficacy was confirmed by the increased expression levels of inducible NO synthase and Th1-type cytokines, IFN-gamma and IL-12 and down-regulation of IL-4, IL-10 and transforming growth factor (TGF)-beta. The results indicate the potentiality of rLdAdoHcy protein as a suitable vaccine candidate against VL. PMID- 26898999 TI - [Current situation and prospect of fetal medicine in China]. PMID- 26899000 TI - [Effect on maternal blood dilution of fetoscopic laser occlusion of chorioangiopagous vessels in treating twin to twin transfusion syndrome]. AB - OBJECTIVE: To evaluate the effect on maternal blood dilution of fetoscopic laser occlusion of chorioangiopagous vessels (FLOC) in treating twin to twin transfusion syndrome (TTTS). METHODS: The clinical data of 71 cases of TTTS who had FLOC in Peking University Third Hospital were reviewed. Fluid intake, blood pressure, heart rate, red blood cell count, hemoglobin and hematocrit in perioperative 24 hours were analyzed. RESULTS: (1) According to the Quintero staging, 9 cases were stage I, 24 were stage II, 28 were stage III and 10 cases were stage IV. (2) The average operation time of FLOC was (64.0+/-16.3) minutes. One case had placental abruption after the procedure; one had placental vessel rupture and 6 women refused to take blood counting. These 8 cases were excluded and 63 cases were included in the study. (3) The perioperative bleeding volume was 3 (1, 5) ml, and the volume of fluid intake, urine, amniotic fluid drainage and net fluid intake in the perioperative 24 hours was 2 050 ml(1 530 ml, 3 700 ml), 2 300 ml (1 100 ml, 3 500 ml), 1 900 ml (1 400 ml, 2 700 ml) and -1 760 ml ( 100 ml, -3 350 ml), respectively. There was no significant difference between maternal blood pressure or heart rate preoperatively and postoperatively. (4) The maternal red blood cell count [(3.47+/-0.36)*10(12)/L versus (3.01+/- 0.37)*10(12)/L, P=0.000], hemoglobin [(107.8+/-12.1) g/L versus (95.1+/-11.2) g/L, P=0.000] and hematocrit [0.313(0.238, 0.387) versus 0.276(0.213, 0.800), P=0.000] decreased significantly 24 hours after FLOC. (5) The postoperative hematocrit decreased more in the group which the amniotic fluid drainage volume was 2 000-3 000 ml than that in the group which the amniotic fluid drainage volume was 1 000-1 999 ml. CONCLUSIONS: The blood dilution can not be ignored after the FLOC in TTTS patients. The more the amniodrainage volume during the FLOC, the more the maternal blood dilution would be. It might result from amniodrainage during the FLOC, improved maternal-placenta circulation and tocolytics used after FLOC. More attention should be take about maternal cardiac function and complications related with anemia after FLOC. PMID- 26899001 TI - [Prenatal diagnosis and intervention to fetal hydrothorax: five cases analysis]. AB - OBJECTIVE: To research the important of prenatal diagnosis and effect of intervention to fetal hydrothorax. METHODS: The cases of fetal hydrothorax (n=5) were obtained from the Shengjing Hospital, China Medical University between December 2014 and May 2015. All pregnancies were uncomplicated, excluded congenital organic and chromosomal abnormalities during prenatal diagnosis and with a 37 average gestational weeks. The case 1, 2, 4 were unilateral hydrothorax and the case 3, 5 were bilateral. We performed an antenatal thracocentesis to case 1, 2, 3. In case1, the hydrothorax increased rapidly after 5 days, and the patient underwent a cesarean section and ex utero intrapartum treatment (EXIT); in case 2, the fetal heart rate was decreased to 40-50 bpm suddenly during thracocentesis, and we performed an emergent cesarean section and EXIT for the patient; in case 3, the patient underwent thracocentesis and a meanwhile cesarean section and EXIT procedure. We performed a conservative management to case 4, 5, the hydrothorax resolved spontaneously during the pregnancy and after birth, both patients underwent cesarean section. RESULTS: All fetuses were survived, the neonates of case 1, 2 and 3 underwent assited mechanical ventilation, thoracic close drainage, then discharged after hydrothorax resolved and feeding tolerance; in case 4, there was no respiratory distress and hospital treatment; in case 5, the neonate underwent assited mechanical ventilation and conservative management, the hydrothorax has resolved gradually. CONCLUSIONS: The prenatal diagnosis and antenatal intervention (thracocentesis) may play an important role in fetal hydrothorax treatment. In clinical, we should choose different plan according to the gestation weeks and classification of hydrothorax of the patient. PMID- 26899002 TI - [Clinical value of prenatal MRI in the diagnosis and differential diagnosis of fetal bronchopulmonary sequestration]. AB - OBJECTIVE: To investigate the clinical value of prenatal MRI in the diagnosis and differential diagnosis of congenital bronchopulmonary sequestration (BPS). METHODS: From January 2009 to December 2014, 16 fetuses with BPS were diagnosed by fetal MRI in Huzhou Maternity and Child Care Hospital and Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine. The clinical data of these cases were analyzed retrospectively. All were singleton pregnancy, and MRI was carried out within 24-48 hours after routine prenatal ultrasound. All the neonates underwent postnatal enhanced CT scan or surgical biopsy after birth, and the results were compared to prenatal MRI diagnosis. RESULTS: (1) With prenatal MRI, 16 cases were diagnosed BPS. The lesions located in left lung in 10 cases, and right lung in 6 cases. As the scope of the lesion, 3 cases located in the whole left lung, 6 cases limited to the left lower lobe, and 1 case was subdiaphragmatic on the left side. 2 cases located in the whole right lung and 4 cases limited to the right lower lobe. One case complicated oligoamnios, and one had pleural effusion. Supplying vessels could be found in 14 cases. (2) When the postnatal results were compared with prenatal MRI, 15 cases were comfirmed as BPS (15/16), including 10 intralobar cases 5 extralobar cases. One that was diagnosed as BPS by prenatal MRI was confirmed to be congenital cystic adenomatoid malformation (CCAM) by pathology. The accuracy of prenatal MRI diagnosis of BPS was 15/16. Prenatal ultrasound missed one case and misdiagnosed two cases, as one was mistakened as CCAM and the other as cystic teratoma. CONCLUSION: Prenatal MRI has good clinical value in the diagnosis and differential diagnosis of fetal BPS. PMID- 26899003 TI - [Clinical evaluation of amniontic products after transcervical resection of intensive degree of intrauterine adhesions]. AB - OBJECTIVE: To evaluate the effect of amniotic products after transcervical resection of uterine adhesions (TCRA). METHODS: This study was carried out in 57 patients with intensive degree of intrauterine adhesions (IUA) who had been treated by TCRA between Jun. 2013 to Jun. 2014. These patients were devided into two groups randomly. In group amnion, 29 patients were placed amniontic scaffold balloon after TCRA; in group balloon, 28 patients were placed Foley's balloon after TCRA. The two groups' balloons were taken out after TCRA 7 days. All patients were taken artificial cycle treatment. The uterine cavity form and the menstruation of 2 groups were observed in 3 months after TCRA. RESULTS: In group amnion, IUA score dropped from 10.1+/-0.5 preoperatively to 3.2+/-1.5 postoperative (P<0.01), in group balloon, IUA score dropped from 10.1+/-0.5 preoperatively to 6.3+/-2.5 postoperative (P<0.01). In group amnion, the menstrual score increased from 13.3 +/- 4.4 preoperatively to 32.6 +/- 5.5 postoperative (P<0.01), in group balloon, the menstrual score increased from 11.1+/-5.8 to 26.5+/-5.6 (P<0.01). The menstrual improvement of group amnion was better than that of group balloon significantly (P=0.002). In group amnion, the recurrence rate of adhesion was 21% (6/29), in group balloon, the recurrence rate of adhesion was 36% (10/28). There was no significant difference (P=0.248). The pregnancy rate of group amnion was 28% (8/29), the pregnancy rate of group balloon was 21% (6/28). The difference of pregnancy rate in two groups was not significant (P=0.760). CONCLUSION: This small sample observation indicate that amniotic products used in the treatment of intensive IUA could improve menstrual, reduce the recurrence of adhesion, but the impovement of the pregnancy rate should be confirmed by large sample observation. PMID- 26899004 TI - [Analysis of the follow-up results concerning pregnancy, delivery and infants after assisted reproductive technique with GnRH-a for luteal support]. AB - OBJECTIVE: To investigate the results of follow-up visits of pregnancy course, delivery and infants of women who got clinically pregnant by assisted reproductive technique after gonadotropin-releasing hormone agonist (GnRH-a) added for luteal support, and to analyse the influence of adding GnRH-a in luteal support on the safety of mother and infant. METHODS: A retrospective analysis was carried out on the medical record from 215 patients who got clinically pregnant after luteal phase long regimen fresh-cycle transfer was operated. According to the differences in luteal support methods, the patients were assigned to Group A (124 patients, progesterone+dydrogesterone group), Group B (91 patients, GnRH-a added group). The patients' pregnancy course, delivery time, and the growth and development of infants within 1-2 years were followed up. RESULTS: (1) There was no obvious difference between Group A and Group B in terms of the abortion ratio during the early pregnancy (8.1%, 12.1%), the rate of abortion villous deformity (50.0%, 9.1%), the rate of heterotopic pregnancy (10.5%, 5.5%) and rate of twin pregnancy (19.4%, 28.6%; all P>0.05). (2) Compared to group A, during the middle and late pregnancy of single or twin pregnancy in Group B , there was no obvious difference in the rate of fetal chromosomal abnormality, organ malformation incidence, late abortion rate and stillbirth rate (all P>0.05). (3) As to childbirth, in the case of twin pregnancy, there was a higher rate of premature delivery (60.0%, 39.1%; P=0.041), as well as rate of lower birth weight of newborn (56.0%, 34.8%; P=0.037) in group B. (4) The statistics on general growth and development as well as infantile common diseases within 2 years after birth indicated that there was no obvious difference between the two groups in single birth and twin birth subgroup (all P>0.05). CONCLUSION: On the basis of controlling of implanted embryos and reducing the occurrence of twins, GnRH-a luteal support maybe relatively safe and effective. PMID- 26899005 TI - [Clinical value of transvaginal ultrasound, MRI and hysteroscopy in the assessment of endometrial cancer lesion size]. AB - OBJECTIVE: To investigate the clinical significance of transvaginal ultrasound, hysteroscopy and MRI in the assessment of endometrial cancer lesions size. METHODS: Data from 56 patients who successively underwent transvaginal ultrasound, MRI and hysteroscopy inspection preoperative endometrial carcinoma were retrospectively analyzed to assess the accuracy of lesions size. RESULTS: The pathologic lesions size measured mean maximum diameter of 56 cases was (3.05+/-0.23) cm, while the mean maximum diameter measured by vaginal ultrasound, MRI and hysteroscopy were respectivelly (2.46+/-0.31) cm, (3.12+/-0.08) cm, and (3.18+/-0.21) cm. Compared with the pathologic measured values, the compliance rates of transvaginal ultrasound, hysteroscopy and MRI were respectively 54% (30/56), 71% (40/56) and 75% (42/56), which vaginal ultrasound measurement value was significantly different than that by pathologic measured (P=0.031), while there were significant difference between the hysteroscopy measured lesion size and pathologic measured, or between MRI measured values and pathologic measured (all P>0.05). CONCLUSION: Preoperative assess the endometrial cancer lesions size, significance of vaginal ultrasound examination is limited, and MRI and hysteroscopy examination is accurate, but easy to over-estimated lesion size. PMID- 26899006 TI - [Expression and clinical significance of Dyrk1b in the specimens and cells of cervical lesions]. AB - OBJECTIVE: To detect and explore the expression and clinical significance of dual specificity tyrosine phosphorylation regulated kinase1b (Dyrk1b) in the specimens and cells of cervical lesions. METHODS: (1) All the data were collected from 75 patients with cervical cancer and 52 cases with squamous intraepithelial lesion (SIL) admitted in the First Affiliated Hospital of Dalian Medical College during Jan. 2011 to Dec. 2013 and confirmed by pathological examination, included 60 cases of stage I and 15 cases of stage II, 12 cases with low-grade squamous intraepithelial lesion (LSIL) and 40 cases with high-grade squamous intraepithelial lesion (HSIL). While, 28 cases with chronic cervicitis were chosen as the control group. The protein expression of Dyrk1b was detected by immunohistochemistry among the four groups. (2) The expression of Dyrk1b in HeLa and SiHa cells were detected by western blot method and the expression of Dyrk1b protein were also detected after treatment of AZ191 (5, 10 MUmol/L) for 48 hours in HeLa and SiHa cells. (3) The cellular survival and proliferation of HeLa and SiHa cells treated by different concentrations of AZ191 (2.5, 5, 10, 25, 50, 100 MUmol/L) for 48 hours were detected by methyl thiazolyl tetrazolium (MTT) assay. (4) The rate of apoptosis of HeLa and SiHa cells was detected by flowcytometry after treatment of AZ191 (5, 10 MUmol/L) for 48 hours. RESULTS: (1) The positive rates of Dyrk1b protein in chronic cervicitis, LSIL, HSIL and cervical squamous cancer by immunohistochemistry were 11%(3/28), 1/12, 42% (17/40) and 71% (53/75), respectively. The expression of Dyrk1b in cervical squamous cancer and HISL were higher than those in LSIL and chronic cervicitis (P<0.01), there were significant difference between cervical squamous cancer and HSIL, or between HSIL and LSIL (all P<0.05), while there were not significant difference between LSIL and chronic cervicitis (P>0.05). Expression of Dyrk1b was correlated with stromal invasion depth of cervical cancer (P<0.05), but not with age, clinical stage, lymph node metastasis, and serum squamous cell carcinom antigen (SCC-Ag) levels (all P>0.05). (2) Dyrk1b protein was expressed in different levels in HeLa and SiHa cells, and the expression of Dyrk1b was decreased gradually as the increased of the concentration of AZ191 in both HeLa and SiHa cells by treatment of AZ191 for 48 hours. (3) Different concentration of AZ191 treated on cervical cancer cells could inhibit the cellular proliferation and induce cell apoptosis in a concentration-dependent manner (P<0.01), concomitant to the decreased cell survival rate. The apoptosis rate of HeLa and SiHa were increased significantly after 10 MUmol/L AZ191-treatment for 48 hours, but no any difference induced by 5 MUmol/L AZ191-treatment compared to control group. Also,there was no any difference between Hela and SiHa cells in either inhibitory effect or apoptosis rate induced by AZ191. CONCLUSIONS: Dyrk1b is over-expressed in either specimens or cells of cervical cancer. The expression of Dyrk1b protein in cervical lesions is increased as the progression of disease. Dyrk1b inhibitor AZ191 could inhibit cellular proliferation and induce apoptosis in a concentration-dependent manner in cervical cancer cells. PMID- 26899008 TI - PAX6 Isoforms, along with Reprogramming Factors, Differentially Regulate the Induction of Cornea-specific Genes. AB - PAX6 is the key transcription factor involved in eye development in humans, but the differential functions of the two PAX6 isoforms, isoform-a and isoform-b, are largely unknown. To reveal their function in the corneal epithelium, PAX6 isoforms, along with reprogramming factors, were transduced into human non-ocular epithelial cells. Herein, we show that the two PAX6 isoforms differentially and cooperatively regulate the expression of genes specific to the structure and functions of the corneal epithelium, particularly keratin 3 (KRT3) and keratin 12 (KRT12). PAX6 isoform-a induced KRT3 expression by targeting its upstream region. KLF4 enhanced this induction. A combination of PAX6 isoform-b, KLF4, and OCT4 induced KRT12 expression. These new findings will contribute to furthering the understanding of the molecular basis of the corneal epithelium specific phenotype. PMID- 26899010 TI - Epigenetic Treatment of Neurodegenerative Disorders: Alzheimer and Parkinson Diseases. AB - Preclinical Research In this review, we discuss epigenetic-driven methods for treating neurodegenerative disorders associated with mitochondrial dysfunction, focusing on carnitinoid antioxidant-histone deacetylase inhibitors that show an ability to reinvigorate synaptic plasticity and protect against neuromotor decline in vivo. Aging remains a major risk factor in patients who progress to dementia, a clinical syndrome typified by decreased mental capacity, including impairments in memory, language skills, and executive function. Energy metabolism and mitochondrial dysfunction are viewed as determinants in the aging process that may afford therapeutic targets for a host of disease conditions, the brain being primary in such thinking. Mitochondrial dysfunction is a core feature in the pathophysiology of both Alzheimer and Parkinson diseases and rare mitochondrial diseases. The potential of new therapies in this area extends to glaucoma and other ophthalmic disorders, migraine, Creutzfeldt-Jakob disease, post-traumatic stress disorder, systemic exertion intolerance disease, and chemotherapy-induced cognitive impairment. An emerging and hopefully more promising approach to addressing these hard-to-treat diseases leverages their sensitivity to activation of master regulators of antioxidant and cytoprotective genes, antioxidant response elements, and mitophagy. Drug Dev Res 77 : 109-123, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26899009 TI - Gastrointestinal bleeding due to pancreatitis-induced splenic vein thrombosis: Treatment with percutaneous splenic vein recanalization. PMID- 26899011 TI - Randomized clinical trial of a new cyanoacrylate flexible tissue adhesive (Adhflex) for repairing surgical wounds. AB - The use of synthetic adhesives such as cyanoacrylates for closing surgical wounds remains controversial. In a multicenter, prospective and randomized clinical trial, we compared a new cyanoacrylate elastic tissue adhesive, Adhflex, with standard suturing methods for repairing surgical wounds. Sixty patients who underwent surgery for inguinal hernia were randomly chosen for Adhflex or standard silk suture. We evaluated wound closure time and parameters related to wound healing and complications using the Hollander Scale; overall surgeon, patient, and independent evaluator satisfaction with scar appearance using a visual analog scale; and scar cosmesis and cosmetic outcome using the Patient and Observer Scar Assessment Scale. The major finding of this study was that surgical wound closure time (minutes) was significantly lower (p < 0.05) when using Adhflex (1.50 +/- 0.63) than when using sutures (2.23 +/- 0.66), reducing surgery costs. Patient, surgeon and independent evaluator satisfaction was greater with Adhflex (p < 0.05). No differences were found in the final cosmetic outcome of surgical wounds (p > 0.05). The results of this clinical trial showed that Adhflex could be considered a promising and suitable wound closure method. Undoubtedly, lower operating room times will reduce overall surgical costs. Cosmetic outcomes in the medium term are comparable to those seen with sutures, yet there is no need for dressing changes, postoperative wound checks, or removal of stitches or clips. The comfort of the patient is an important factor when considering wound closure methods. REGISTRATION NUMBER: Eudra CT2012-002701-22. PMID- 26899012 TI - Agronomic application of olive mill wastewater: Effects on maize production and soil properties. AB - This study investigates the effect of direct amendment of olive mill wastewater (OMW) on the fertility of soil, described as poor in the area of Marrakech (semi arid region) in Morocco. The treated plots were amended with untreated OMW generated by a traditional extraction process at the amount of 10 L/m(2)/year during two consecutive years. Results of these two years treatments with crude OMW at relatively high dose reveal an important increase in soil physicochemical characteristics, namely electric conductivity (EC), Na(+,) K(+), phosphorus, nitrogen, organic matter and soluble phenolic compounds. EC of treated soil was enhanced from 0.34 to 2.91 mS/cm as compared to the control soil. After spreading OMW in soil, the amounts of its nutritive elements increased by 81% for nitrogen, 66% for phosphorus and 88% for potassium. The accumulation of phenolic compounds and the increase of total peroxidase activity in plants provide evidence of their protective role against the physiological stress induced by OMW. However, this enrichment in mineral and nutritive elements decreased three months after OMW application, revealing OMW biodegradation in the studied calcareous soil. In parallel, an increase in the contents of the soluble phenolic compounds on the upper layer of soil was denoted and maize plants growth was efficiently raised. Significant amelioration was obtained notably in terms of fresh and dry weight of leaves, leaves area, spikes fresh and dry weight, 100 seeds weight and straw yield (37, 54, 27, 24, 14 and 9% respectively). Along with the correct choice of convenient soils notably calcareous ones and tolerant crops such as maize, this method could constitute an efficient approach for avoiding problems attributed to the uncontrolled disposal of these effluents and an effective strategy to regenerate degraded soils and represents an economical alternative that provides a local fertilizer. PMID- 26899013 TI - Acoustic emission diagnosis for human joint cartilage diseases. AB - PURPOSE: The topic of the presented paper concerns the diagnosis of the wear and diseases of human joint cartilage performed by the acoustic waves emission. The aim of this paper is the determining of the necessary parameters for the diagnosis about the wear and diseases of human joint cartilage. MATERIAL AND METHOD: To the research methods used in this paper belong the evaluation of measurement results of the cartilage surface samples obtained by means of laser and mechanical sensor and acoustic emission wave might or voltage gained from the AE apparatus during the treatments performed for normal and pathological used and not used human knee and hip joints. RESULTS: The results concern with the corollaries which are implied from reading values gained by virtue of the acoustic emission Apparatus, and from observations from cartilage surface pictures obtained from laser and mechanical sensors. The diagnose of concrete cartilage illness depends on the proper relative values of obtained strongest of generated AE wave as well as the shapes and amplitudes of acoustic waves and wave frequencies. CONCLUSIONS: The main conclusions obtained in this paper are as follows: connections between synovial fluid dynamic viscosity or friction forces and intensity of acoustic emission values, the determination of the type of lesions and deformations of the human joint cartilage surface by means of the shapes architecture of the acoustic emission waves. Moreover are indicated the necessary conditions for the diagnosis of the such dieses as: pathological cartilage with arthritic or osteoporosis or rheumatology changes. PMID- 26899014 TI - Chewing lice (Phthiraptera) from wild birds in southern Portugal. AB - This study was carried out to determine chewing louse species of wild birds in the Ria Formosa Natural Park, located in southern Portugal. In addition, the hypothesis that bird age, avian migration and social behaviour have an impact on the louse prevalence was tested. Between September and December of 2013, 122 birds (belonging to 10 orders, 19 families, 31 genera and 35 species) captured in scientific ringing sessions and admitted to the Wildlife Rehabilitation and Investigation Centre of Ria Formosa were examined for lice. Twenty-six (21.3%) birds were found to be infested with at least one chewing louse species. The chewing lice identified include 18 species. Colonial birds (34.9%) and migratory birds (29.5%) had statistically significant higher prevalence than territorial birds (6.8%) and resident birds (13.1%), respectively. This paper records 17 louse species for the first time in southern Portugal: Laemobothrion maximum, Laemobothrion vulturis, Actornithophilus piceus lari, Actornithophilus umbrinus, Austromenopon lutescens, Colpocephalum heterosoma, Colpocephalum turbinatum, Eidmanniella pustulosa, Nosopon casteli, Pectinopygus bassani, Pseudomenopon pilosum, Trinoton femoratum, Trinoton querquedulae, Craspedorrhynchus platystomus, Degeeriella fulva, Falcolipeurus quadripustulatus, Lunaceps schismatus. Also a nymph of the genus Strigiphilus was collected from a Eurasian eagle-owl. These findings contribute to the knowledge of avian chewing lice from important birds areas in Portugal. PMID- 26899007 TI - Genome analysis of three Pneumocystis species reveals adaptation mechanisms to life exclusively in mammalian hosts. AB - Pneumocystis jirovecii is a major cause of life-threatening pneumonia in immunosuppressed patients including transplant recipients and those with HIV/AIDS, yet surprisingly little is known about the biology of this fungal pathogen. Here we report near complete genome assemblies for three Pneumocystis species that infect humans, rats and mice. Pneumocystis genomes are highly compact relative to other fungi, with substantial reductions of ribosomal RNA genes, transporters, transcription factors and many metabolic pathways, but contain expansions of surface proteins, especially a unique and complex surface glycoprotein superfamily, as well as proteases and RNA processing proteins. Unexpectedly, the key fungal cell wall components chitin and outer chain N mannans are absent, based on genome content and experimental validation. Our findings suggest that Pneumocystis has developed unique mechanisms of adaptation to life exclusively in mammalian hosts, including dependence on the lungs for gas and nutrients and highly efficient strategies to escape both host innate and acquired immune defenses. PMID- 26899015 TI - Identification of a novel HLA-B*54:34 allele by polymerase chain reaction sequence-based typing in a Chinese leukemia patient. AB - HLA-B*54:34 is different from HLA-A*54:01:01 by a single nucleotide substitution at position 343 G>A. PMID- 26899016 TI - Fluorescent Bioactive Corrole Grafted-Chitosan Films. AB - Transparent corrole grafted-chitosan films were prepared by chemical modification of chitosan with a corrole macrocycle, namely, 5,10,15 tris(pentafluorophenyl)corrole (TPFC), followed by solvent casting. The obtained films were characterized in terms of absorption spectra (UV-vis), FLIM (fluorescence lifetime imaging microscopy), structure (FTIR, XPS), thermal stability (TGA), thermomechanical properties (DMA), and antibacterial activity. The results showed that the chemical grafting of chitosan with corrole units did not affect its film-forming ability and that the grafting yield increased with the reaction time. The obtained transparent films presented fluorescence which increases with the amount of grafted corrole units. Additionally, all films showed bacteriostatic effect against S. aureus, as well as good thermomechanical properties and thermal stability. Considering these features, promising applications may be envisaged for these corrole-chitosan films, such as biosensors, bioimaging agents, and bioactive optical devices. PMID- 26899017 TI - Percutaneous coronary intervention for chronic total occlusion improved prognosis in patients with renal insufficiency at high risk of contrast-induced nephropathy. AB - We investigated whether attempted percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) would improve the prognosis in patients with renal insufficiency at high risk of contrast-induced nephropathy (CIN). We analyzed 2,330 consecutive patients with renal insufficiency with or without CTOs who underwent coronary angiography or PCI from prospectively collected data. The long term death and risk of CIN were evaluated among three groups: patients without CTOs (group A, n = 1,829), patients with un-attempted PCI for CTOs (group B, n = 142), and patients who underwent attempted PCI for CTOs (group C, n = 359). Overall, group B and group C (successful rate, 89%) patients had similar renal function and were not significantly associated with an increased risk of CIN (adjusted odds ratio [OR] = 0.88, 95% confidence interval [CI]: 0.41-1.93, P = 0.758). During a 2.33-year period (median), multivariate analysis demonstrated that attempted PCI for CTOs was independently associated with lower mortality (adjusted hazard ratio for death: 0.38, 95% CI: 0.18-0.83; P = 0.015). Attempted PCI for CTOs improved the long-term prognosis in patients with high-risk renal insufficiency and did not increase the risk of CIN. PMID- 26899018 TI - Droplet Breakup in Expansion-contraction Microchannels. AB - We investigate the influences of expansion-contraction microchannels on droplet breakup in capillary microfluidic devices. With variations in channel dimension, local shear stresses at the injection nozzle and focusing orifice vary, significantly impacting flow behavior including droplet breakup locations and breakup modes. We observe transition of droplet breakup location from focusing orifice to injection nozzle, and three distinct types of recently-reported tip multi-breaking modes. By balancing local shear stresses and interfacial tension effects, we determine the critical condition for breakup location transition, and characterize the tip-multi-breaking mode quantitatively. In addition, we identify the mechanism responsible for the periodic oscillation of inner fluid tip in tip multi-breaking mode. Our results offer fundamental understanding of two-phase flow behaviors in expansion-contraction microstructures, and would benefit droplet generation, manipulation and design of microfluidic devices. PMID- 26899019 TI - Prognostic and Predictive Effect of TP53 Mutations in Patients with Non-Small Cell Lung Cancer from Adjuvant Cisplatin-Based Therapy Randomized Trials: A LACE Bio Pooled Analysis. AB - INTRODUCTION: Tumor protein p53 gene (TP53) mutations are common in stage I through III non-small cell lung cancer, but clinical trials have shown inconsistent results regarding their relationship to the effects of adjuvant therapy. The objective is to clarify their putative prognostic and predictive effects. METHODS: A pooled analysis of TP53 mutations (exons 5-8) was conducted in four randomized trials (the International Adjuvant Lung Cancer Trial, J BRonchus 10, Cancer and Leukemia Group B-9633, and Adjuvant Navelbine International Trialist Association trial) of platinum-based adjuvant chemotherapy (ACT) versus observation (OBS). Hazard ratios (HRs) and 95% confidence intervals (CIs) of mutant versus wild-type (WT) TP53 for overall survival (OS) and disease free survival (DFS) were estimated using a multivariable Cox model stratified on trial and adjusted on sex, age, and clinicopathological variables. Predictive value was evaluated with an interaction between treatment and TP53. RESULTS: A total of 1209 patients (median follow-up 5.5 years) were included. There were 573 deaths (47%) and 653 DFS events (54%). Mutations (434 [36%]) had no prognostic effect (OBS HROS = 0.99, 95% CI: 0.77-1.28, p = 0.95; HRDFS = 0.99, 95% CI: 0.78 1.25, p = 0.92) but were marginally predictive of benefit from ACT for OS (test for interaction: OS, p = 0.06; DFS, p = 0.11). Patients with WT TP53 had a tendency toward better outcomes with ACT than did those in the OBS group (HROS = 0.77, 95% CI: 0.62-0.95, p = 0.02; HRDFS = 0.75, 95% CI: 0.62-0.92, p = 0.005). In the ACT arm, a deleterious effect of mutant versus WT TP53 was observed (HROS = 1.40, 95% CI: 1.10-1.78, p = 0.006; HRDFS = 1.31, 95% CI: 1.04-1.64, p = 0.02). CONCLUSIONS: TP53 mutation had no prognostic effect but was marginally predictive for survival from ACT. In patients who received ACT, TP53 mutation tended to be associated with shorter survival than wild-type TP53. PMID- 26899020 TI - Evaluation of the performance of the ACS NSQIP surgical risk calculator in gynecologic oncology patients undergoing laparotomy. AB - OBJECTIVE: The objective of this study was to evaluate the ability of the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) surgical risk calculator to predict complications in gynecologic oncology patients undergoing laparotomy. METHODS: A chart review of patients who underwent laparotomy on the gynecologic oncology service at a single academic hospital from January 2009 to December 2013 was performed. Preoperative variables were abstracted and NSQIP surgical risk scores were calculated. The risk of any complication, serious complication, death, urinary tract infection, venous thromboembolism, cardiac event, renal complication, pneumonia and surgical site infection were correlated with actual patient outcomes using logistic regression. The c-statistic and Brier score were used to calculate the prediction capability of the risk calculator. RESULTS: Of the 1094 patients reviewed, the majority were <65years old (70.9%), independent (95.2%), ASA class 1-2 (67.3%), and overweight or obese (76.1%). Higher calculated risk scores were associated with an increased risk of the actual complication occurring for all events (p<0.05). The calculator performed best for predicting death (c-statistic=0.851, Brier=0.008), renal failure (c-statistic=0.752, Brier=0.015) and cardiac complications (c statistic=0.708, Brier=0.011). The calculator did not accurately predict most complications. CONCLUSIONS: The NSQIP surgical risk calculator adequately predicts specific serious complications, such as postoperative death and cardiac complications. However, the overall performance of the calculator was worse for gynecologic oncology patients than reported in general surgery patients. A tailored prediction model may be needed for this patient population. PMID- 26899021 TI - The first MCL-1-selective BH3 mimetics have therapeutic potential for chronic lymphocytic leukemia. AB - Small-molecule BH3 mimetics are designed to mimic the BH3 domain of BH3-only BCL 2 family members which are antagonists of the prosurvival members (such as BCL-2, BCL-XL and MCL-1). The BH3 mimetics are intended to bind with high affinity to prosurvival proteins, in order to inhibit their functional activity and hence to induce apoptosis in cancer cells. Both navitoclax (BCL-2/BCL-XL antagonist) and ABT-199/venetoclax (BCL-2-selective inhibitor) have demonstrated therapeutic efficacy especially in chronic lymphocytic leukemia (CLL). However, these BH3 mimetics cannot antagonize the prosurvival protein MCL-1 that is overexpressed and involved in therapeutic resistance in CLL. Furthermore, until now, none of the reported small-molecule MCL-1 inhibitors bound to their target with high affinity. The first MCL-1-selective BH3 mimetics capable of high-affinity binding and inducing apoptosis in cancer cells through an on-target mechanism have just been identified. This discovery should advance the translational research to implement novel drugs in treating CLL. PMID- 26899022 TI - Is the cardiovascular toxicity of NSAIDS and COX-2 selective inhibitors underestimated in patients with haemophilia? AB - Joint pain secondary to chronic arthropathy represents one of the most common and debilitating complications of haemophilia, often requiring analgesic care. When compared with nonselective non-steroidal anti-inflammatory drugs (ns-NSAIDs), selective COX-2 inhibitors (coxibs) offer the major advantage of not increasing the bleeding risk, thus being a better choice of analgesics for haemophilia patients. However, several studies have highlighted the cardiovascular risks posed by coxibs and NSAIDs. Given the assumed protection against thrombosis conferred by the deficiency in coagulation factors VIII or IX, these precautions regarding the use of coxibs and NSAIDs have never really been taken into account in haemophilia management. However, contrary to what has long been suspected, haemophilia patients are indeed affected by the same cardiovascular risk factors as nonhaemophiliac patients. Further studies should be conducted to evaluate the impact of NSAIDs on cardiovascular risks and the prevalence of hypertension in haemophilia patients. PMID- 26899023 TI - Clinical Value of Hypochromia Markers in the Detection of Latent Iron Deficiency in Nonanemic Premenopausal Women. AB - BACKGROUND: Iron deficiency (ID) is the most common cause of anemia in fertile women and hemoglobin (Hb) within the reference interval does not exclude ID. The consequence of an imbalance between the iron requirements and supply is a reduction of red-cell Hb content, which causes hypochromic cells. The aim of this study was to assess the reliability of new parameters low Hb density (LHD%), reticulocyte Hb equivalent (RetHe), and percentage of hypochromic erythrocytes (%HypoHe) in the detection of latent ID (LID), defined as depletion of iron stores without anemia. METHODS: Two hundred fifty consecutive nonanemic women in fertile age (18-40 years, mean 33.5 years), whose analyses had been requested by general practitioners, were included. Independent samples t-test, receiver operating characteristic (ROC) curve analysis (gold standard for detecting LID ferritin <30 MUg/l), and Cohen's kappa index were applied. RESULTS: One hundred fifty-three women had ferritin within the reference range and Hb >120 g/L; 97 (38.8%) had LID. The results were as follows: %HypoHe-AUC 0.934, cutoff 1.6%, sensitivity 85.7%, specificity 92.1%; RetHe-AUC 0.914, cutoff 29.9 pg, sensitivity 86.8%, specificity 85.7%; LHD%-AUC 0.898, cutoff 5.0%, sensitivity 85.9%, specificity 84.1%. Applying those cutoffs, agreement between ferritin and %HypoHe was kappa 0.61 and 0.56 for RetHe and LHD%. CONCLUSIONS: LHD%, %HypoHe, and RetHe emerge as reliable tests for the investigation of LID and could improve the ability to detect ID before anemia is present. PMID- 26899024 TI - A Complete Overhaul of the Electron Energy-Loss Spectroscopy and X-Ray Absorption Spectroscopy Database: eelsdb.eu. AB - The electron energy-loss spectroscopy (EELS) and X-ray absorption spectroscopy (XAS) database has been completely rewritten, with an improved design, user interface, and a number of new tools. The database is accessible at https://eelsdb.eu/ and can now be used without registration. The submission process has been streamlined to encourage spectrum submissions and the new design gives greater emphasis on contributors' original work by highlighting their papers. With numerous new filters and a powerful search function, it is now simple to explore the database of several hundred EELS and XAS spectra. Interactive plots allow spectra to be overlaid, facilitating online comparison. An application-programming interface has been created, allowing external tools and software to easily access the information held within the database. In addition to the database itself, users can post and manage job adverts and read the latest news and events regarding the EELS and XAS communities. In accordance with the ongoing drive toward open access data increasingly demanded by funding bodies, the database will facilitate open access data sharing of EELS and XAS spectra. PMID- 26899025 TI - Safety and efficacy of once daily ledipasvir/sofosbuvir fixed-dose combination in patients with chronic hepatitis C. AB - INTRODUCTION: During the past couple of years, the regulatory authorities have approved seven new direct-acting antivirals (DAAs) for the treatment of chronic hepatitis C (CHC). In 2014, the US FDA approved the fixed dose combination of ledipasvir (LDV) plus sofosbuvir (SOF) for the treatment of genotype (GT) 1 HCV and the European Commission Granted its marketing authorization to treat patients with GT1 and 4. This regimen showed outstanding rates of virologic response along with a favorable safety profile with a very low rate of both virologic failure and treatment discontinuation. AREAS COVERED: In this review, we sought to review the pharmacokinetics, clinical efficacy and safety profile pertaining to LDV/SOF combination in treatment of CHC with special emphasis on phase III clinical trials. EXPERT OPINION: In all phase III trials, the 12-week course of this new interferon (IFN)-sparing regimen has delivered high virologic cure rates among patient with GT1 and 4 both treatment-naive and - experienced Data about its effectiveness in patients under 18 years of age, end-stage renal disease and patients with significant other organ involvement are eagerly awaited. PMID- 26899026 TI - Serotonin promotes feminization of the sexually dimorphic nucleus of the preoptic area, but not the calbindin cell group. AB - Testosterone and its metabolites masculinize the brain during a critical perinatal window, including the relative volume of sexually dimorphic brain areas such as the sexually dimorphic nucleus of the preoptic area (SDN), which is larger in males than females. Serotonin (5HT) may mediate this hormone action, since 5HT given during the second week of life decreases (i.e., feminizes) SDN volume in males and testosterone-treated females. Although previous work indicates that the 5HT2A/2C receptor is sufficient to induce feminization, it is unclear whether other serotonin receptors are required and which subpopulation(s) of SDN cells are specifically organized by 5HT. Therefore, we injected male and female Sprague-Dawley rat pups with saline, a nonselective 5HTR agonist, a 5HT2A/2C agonist, or a 5HT2A/2C antagonist over several timecourses in early life, and measured the Nissl-SDN as well as a calbindin+ subdivision of the SDN, the CALB-SDN. When examined on postnatal day 18 or early adulthood, the size of the Nissl-SDN was feminized in males treated with any of the serotonergic drugs, eliminating the typical sex difference. In contrast, the sex difference in CALB SDN size was maintained regardless of serotoninergic drug treatment. This pattern suggests that although gonadal hormones shape the whole SDN, individual cellular phenotypes respond to different intermediary signals to become sexually dimorphic. Specifically, 5HT mediates sexual differentiation of non-calbindin population(s) within the SDN. The results also caution against using measurement of the CALB-SDN in isolation, as the absence of an effect on the CALB-SDN does not preclude an effect on the overall nucleus. (c) 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1241-1253, 2016. PMID- 26899027 TI - Troponin T in Prediction of Culprit Lesion Coronary Artery Disease and 1-Year Major Adverse Cerebral and Cardiovascular Events in Patients with Acute Stroke. AB - Troponin T (TnT) elevation above the 99th percentile upper reference limit (URL) is considered diagnostic of acute myocardial infarction (MI). Non-specific increases of TnT are frequent in acute stroke patients. However, in these patients, correct diagnosis of MI is crucial because the antithrombotic medications used to treat acute MI might be harmful and produce intracranial bleeding. In this study, we aimed to associate enhanced TnT levels defined by different cutoff values with occurrence of culprit lesion coronary artery disease (CAD) as well as 1-year major adverse cerebral and cardiovascular events (MACCEs). In this cohort study, we investigated 84 consecutive patients with acute ischemic stroke and concomitant MI. TnT levels were measured using a fourth generation TnT assay. The incidence of culprit lesion CAD was determined by coronary angiography. MACCEs were recorded during 1-year follow-up. Culprit lesion CAD occurred in 55 % of patients, and 1-year MACCE in 37 %. TnT levels above the manufacturers' provided 99th URL (TnT > 0.01) were not associated with culprit lesion CAD (relative risk [RR], 1.3; 95 % confidence interval [CI] 0.96 1.8; P = 0.09). Slightly increased cutoff level (TnT > 0.03) increased specificity and was associated with culprit lesion CAD without decreasing sensitivity (RR, 1.5; 95 % CI 1.1-2.2; P = 0.021) and 1-year MACCE (RR, 1.7; 95 % CI 1.3-2.3; P < 0.001). Slightly increasement of the TnT cutoff level predicted MACCEs and is superior in prediction of culprit lesion CAD in stroke patients without being less sensitive. This finding has to be confirmed in large-scale clinical trials. PMID- 26899028 TI - Element distribution over the surface of fish scales and its connection to the geochemical environment of habitats: a potential biogeochemical tag. AB - The elemental content of fish scales is known to be a reliable biogeochemical tag for tracing the origin of fishes. In this study, this correlation is further confirmed to exist on the surface of fish scales using a novel environmental analytical method, laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), which bypasses several complicated sample preparation procedures such as acid digestion and pre-concentration. The results suggest that the elemental ratios of Sr/Ca, Ba/Ca, and Mn/Ca on the surface of fish scales are strongly correlated with the geochemical environment of their original habitat. This correlation is further demonstrated to be sensitive to variation of water in the habitat due to the adsorbed inorganic ions. In this sense, the limitation of fish scales as a biogeochemical tag is the sensitivity of LA-ICP-MS toward the studied elements. Graphical abstract Illustration of the connection between element distribution pattern over the surface of fish scales and biogeochemical environment of its habitat. PMID- 26899029 TI - Pioneering investigation of the characteristics and elemental concentrations in the environment of the declining Wadi Maryut Lake. AB - Wadi Maryut Lake is one of the remaining parts of the ancient Lake Mareotis and is not mentioned in the scientific literature. For the first time, physical and chemical characteristics as well as elemental concentrations in sediment, water, soil, and plants were determined. The lowest metal pollution indices are in the northeastern end of the lake and tend to increase toward the other end. In lake aquatic environment, Al, Fe, K, Mn, Na, B, and Cr are more likely to exist in insoluble form in the southwestern part and in soluble form in the northeastern part. Using different approaches to assess sediment contamination demonstrates that sediments can be categorized as unpolluted. However, the geo-accumulation index suggests that two locations have low anthropogenic influence of Pb and the enrichment factors and the degree of contamination indicate that Co and Pb may be enriched in sediment of some locations. Comparisons with consensus-based sediment quality guidelines revealed that no sample exceeded the probable effect concentration for Cr, Cu, Ni, Pb, and Zn. The most mobile elements in sediment water and soil-plant systems are Na, K, and Pb. In sediment-water system, Al, Fe, and Mn oxides have the major influence on scavenging of B, K, and Cr. Similarity in the occurrences of Mn, K, and Fe in soil and Mn and Fe in wild plant was found. This work demonstrates the state of decontamination of the lake and confirms its importance as a reference and comparative case for south Mediterranean coastal water bodies. PMID- 26899030 TI - The effects of abscisic acid (ABA) addition on cadmium accumulation of two ecotypes of Solanum photeinocarpum. AB - The study of the effects of exogenous abscisic acid (ABA) addition on cadmium (Cd) accumulation of two ecotypes (mining and farmland) of Solanum photeinocarpum was operated through a pot experiment. The results showed that the biomass and chlorophyll content of the two ecotypes of S. photeinocarpum increased with increasing ABA concentration. Applying exogenous ABA increased Cd content in the two ecotypes of S. photeinocarpum. The maximum Cd contents in shoots of the two ecotypes of S. photeinocarpum were obtained at 20 MUmol/L ABA; shoot Cd contents respectively for the mining and farmland ecotypes were 33.92 and 24.71% higher than those for the control. Applying exogenous ABA also increased Cd extraction by the two ecotypes of S. photeinocarpum, and the highest Cd extraction was obtained at 20 MUmol/L ABA with 569.42 MUg/plant in shoots of the mining ecotype and 520.51 MUg/plant in shoots of the farmland ecotype respectively. Therefore, exogenous ABA can be used for enhancing the Cd extraction ability of S. photeinocarpum, and 20 MUmol/L ABA was the optimal dose. PMID- 26899031 TI - Monitoring of essential and heavy metals in green tea from different geographical origins. AB - The present study measured the concentrations of toxic metals (Cd, Pb) and other elements (Ca, K, Mg, Na, P, Mn, Fe, Zn, Cu, Co, Cr, Ni) in tea leaves and their infusions. The total metal contents were determined by atomic absorption spectrometry. Phosphorus concentration was determined using an ultraviolet visible spectrophotometer. Assessment of the mineral composition enabled determination of the leaching percentage and the risk of exceeding provisional tolerable weekly intake for Cd through daily tea consumption. The concentrations of bioelements were analyzed based on the recommended daily intake values for each. According to recently established standards, green tea was found to be a rich source of Mn. The average Pb and Cd levels in a 200-mL beverage were 0.002 and 0.003 mg, respectively. Indian teas had the highest percentage of Cd leaching (43.8%) and Chinese tea had the lowest (9.41%). Multivariate analysis techniques such as factor analysis and cluster analysis were used to differentiate samples according to geographical origin (China, India, or Japan). Potassium, P, Mn, Fe, Cu, Co, and Cd were effective descriptors for the identification of tea samples from China, India, and Japan. PMID- 26899033 TI - Are porcine flexor digitorum profundus tendons suitable graft substitutes for human hamstring tendons in biomechanical in vitro-studies? AB - INTRODUCTION: Although a plenty of studies exist assessing the strength of ligamentous fixation techniques using porcine flexor digitorum profundus tendons as graft substitutes for human hamstring tendons, there is no biomechanical study comparing these two tendons. To interpret the results obtained with porcine flexor digitorum profundus tendons, knowledge of their biomechanical properties is essential. The purpose of this study was to compare the biomechanical properties of human hamstring tendons and porcine flexor digitorum profundus tendons. MATERIALS AND METHODS: A total of six human hamstring tendons and six porcine flexor digitorum profundus tendons were analysed in this study. Quadruple bundle human hamstring tendons and double-bundle porcine flexor digitorum profundus tendons with a diameter of 9 mm were used. Specimens were placed into a tensile loading fixation of a servohydraulic testing machine. Biomechanical analysis included pretensioning of the constructs at 50 N for 10 min following cyclic loading of 1500 cycles between 50 and 200 N at 0.5 Hz for measurement of elongation. Subsequently, ultimate failure load and failure mode analysis were performed with a ramp speed of 20 mm/min. RESULTS: Human hamstring tendons showed significantly higher maximum load to failure values compared to porcine flexor digitorum profundus tendons (1597 +/- 179.6 N vs. 1109 +/- 101.9 N; p = 0.035). Human hamstring tendons yielded significantly lower initial elongation during preload, but not during cyclical loading. CONCLUSIONS: When porcine flexor digitorum profundus tendons are used as graft substitutes for human hamstring tendons in biomechanical studies, maximum load to failure is underestimated while elongation is comparable to that of human hamstring tendons. Transferring results of biomechanical studies into clinical practice, the lower maximum load to failure of porcine flexor digitorum profundus tendons needs to be taken into consideration. PMID- 26899032 TI - Insight into Coenzyme A cofactor binding and the mechanism of acyl-transfer in an acylating aldehyde dehydrogenase from Clostridium phytofermentans. AB - The breakdown of fucose and rhamnose released from plant cell walls by the cellulolytic soil bacterium Clostridium phytofermentans produces toxic aldehyde intermediates. To enable growth on these carbon sources, the pathway for the breakdown of fucose and rhamnose is encapsulated within a bacterial microcompartment (BMC). These proteinaceous organelles sequester the toxic aldehyde intermediates and allow the efficient action of acylating aldehyde dehydrogenase enzymes to produce an acyl-CoA that is ultimately used in substrate level phosphorylation to produce ATP. Here we analyse the kinetics of the aldehyde dehydrogenase enzyme from the fucose/rhamnose utilisation BMC with different short-chain fatty aldehydes and show that it has activity against substrates with up to six carbon atoms, with optimal activity against propionaldehyde. We have also determined the X-ray crystal structure of this enzyme in complex with CoA and show that the adenine nucleotide of this cofactor is bound in a distinct pocket to the same group in NAD(+). This work is the first report of the structure of CoA bound to an aldehyde dehydrogenase enzyme and our crystallographic model provides important insight into the differences within the active site that distinguish the acylating from non-acylating aldehyde dehydrogenase enzymes. PMID- 26899034 TI - Effects of mesenchymal stem cell-derived cytokines on the functional properties of endothelial progenitor cells. AB - Human mesenchymal stem cell (hMSC) is a potential source for cell therapy due to its property to promote tissue repair. Although, it has been known that hMSCs promote tissue repair via angiogenic cytokines, the interaction between hMSC derived cytokines and the endothelial progenitor cells (EPCs), which play an important role in tissue neovascularization, is poorly characterized. We investigate the effect of cytokine released from different sources of hMSCs including bone marrow and gestational tissues on the EPC functions in vitro. The migration, extracellular matrix invasion and vessel formation of EPCs were studied in the presence or absence of cytokines released from various sources of hMSCs using transwell culture system. The migration of EPCs was highest when co culture with secretory factors from placenta-derived hMSCs (PL-hMSCs) compared to those co-culture with other sources of hMSCs. For invasion and vessel formation, secretory factors from bone marrow-derived hMSCs (BM-hMSCs) could produce the maximal enhancement compared to other sources. We further identified the secreted cytokines and found that the migratory-enhancing cytokine from PL-hMSCs was PDGF BB while the enhancing cytokine from BM-hMSCs on invasion was IGF-1. For vessel formation, the cytokines released from BM-hMSCs were IGF1 and SDF-1. In conclusion, hMSCs can release angiogenic cytokines which increase the migration, invasion and vessel forming capacity of EPCs. We can then use hMSCs as a source of angiogenic cytokines to induce neovascularization in injured/ischemic tissues. PMID- 26899035 TI - Rotator cuff repair using an original iliotibial ligament with a bone block patch: preliminary results with a 24-month follow-up period. AB - BACKGROUND: Our first-line choice of surgical method for massive shoulder rotator cuff tears not amenable to primary repair is a patching method that uses a graft consisting of a section of the iliotibial band with an attached bone block. The objective of this study was to examine the functional and structural results. METHODS: The study included 5 patients who were not eligible for primary repair, received iliotibial band autografts with an attached bone block, and could be monitored for 2 years or more. The grafting method involved suturing the ligament part of the graft to the remaining rotator cuff and fixing the bone part to the greater tubercle of the humerus by means of a suture-bridge technique. Clinical evaluation was performed for 24 months postoperatively. Postoperative structural evaluation was performed using computed tomography at 3 to 4 months and magnetic resonance imaging at 6, 12, and 24 months. RESULTS: A clear improvement was seen at the final clinical evaluation. Fusion of the bone graft with the greater tubercle of the humerus was confirmed on computed tomography in all patients. No retearing was observed on magnetic resonance imaging at the 24-month point, and the thickness of the ligament part of the graft was maintained. CONCLUSION: The patching method using an iliotibial band with an attached bone block as the graft enabled good reconstruction of the rotator cuff, including the greater tubercle footprint. Moreover, good clinical results were seen at 24 months. PMID- 26899036 TI - Predominance of the critical shoulder angle in the pathogenesis of degenerative diseases of the shoulder. AB - HYPOTHESIS: The critical shoulder angle (CSA) could be responsible for cuff tears and concentric osteoarthritis. We aimed to assess this association when potential confounding factors were excluded and to test the hypothesis that more extreme CSAs are associated with larger tears and more severe osteoarthritis. METHODS: The study cohort was composed of 200 patients with primary concentric osteoarthritis (40 patients), isolated supraspinatus tears (40 patients), cuff tears involving at least the supraspinatus and infraspinatus (40 patients), and no history of shoulder problems (control group, 80 patients). Data pertaining to CSA, age, gender, dominant arm, smoking, hypertension, body mass index, and type of work were collected. RESULTS: The average CSA angle was 34 degrees +/- 3 degrees in the control group, 36 degrees +/- 3 degrees with supraspinatus tears, 40 degrees +/- 3.5 degrees with supraspinatus and infraspinatus tears, and 28 degrees +/- 2 degrees with concentric osteoarthritis. Patients with large cuff tears had a significantly greater CSA compared with those with isolated supraspinatus tears (P = .03). The CSA (odds, 1.7; confidence interval [CI], 1.4-2.0) was the most relevant risk factor for cuff tears. The Spearman coefficient between CSA and grade of eccentric osteoarthritis was 0.4 (P = .01). The 2 significant risk factors for concentric osteoarthritis were the CSA (odds, 0.5; CI 0.4-0.6) and age (odds, 1.1; CI, 1.0-1.2). CONCLUSION: Larger CSAs are associated with increased risk of symptomatic cuff tears, larger cuff tears, and the severity of eccentric osteoarthritis. Smaller angles increased the risk and severity of concentric symptomatic osteoarthritis. These associations remained significant even after removal of some of the potentially confounding variables. PMID- 26899037 TI - Protein and Macromolecular Separations. PMID- 26899038 TI - Bath thermal waters in the treatment of knee osteoarthritis: a randomized controlled clinical trial. AB - BACKGROUND: Osteoarthritis is a degenerative disease associated with pain, reduced range of motion, and impaired function. Balneotherapy or bathing in thermal or mineral waters is used as a non-invasive treatment for various rheumatic diseases. AIM: To evaluate the effectiveness of hot sulfurous and non sulfurous waters in the treatment of knee osteoarthritis. DESIGN: A randomized, assessor-blind, controlled trial. SETTING: A spa resort. POPULATION: One hundred and forty patients of both genders, mean age of 64.8+/-8.9 years, with knee osteoarthritis and chronic knee pain. METHODS: Patients were randomized into three groups: the sulfurous water (SW) group (N.=47), non-sulfurous water (NSW) group (N.=50), or control group (N.=43) who received no treatment. Patients were not blinded to treatment allocation. Treatment groups received 30 individual thermal baths (three 20-minute baths a week for 10 weeks) at 37-39 degrees C. The outcome measures were pain (visual analog scale, VAS), physical function (Western Ontario and McMaster Universities Osteoarthritis Index, WOMAC; Lequesne Algofunctional Index, LAFI; Stanford Health Assessment Questionnaire, HAQ), and use of pain medication. Patients were assessed before treatment (T1), at treatment endpoint (T2), and two months post-intervention (T3). Intra- and intergroup comparisons were performed at a significance level of 0.05 (P<0.05). RESULTS: A significant decrease in VAS pain scores (pain during movement, at rest, and at night) and use of pain medication, and improvement in WOMAC, LAFI and HAQ scores were observed from baseline to T2 and T3 within treatment groups (P<0.001), and between controls and both treatment groups at T2 and T3 (P<0.001). No significant differences in these variables were observed between treatment groups at T2, but patients in the SW group reported less pain and better functional status than those in the NSW group at T3, showing a lasting effect of sulfurous water baths. CONCLUSIONS: Both therapeutic methods were effective in the treatment of knee osteoarthritis; however, sulfurous baths yielded longer lasting effects than non-sulfurous water baths. CLINICAL REHABILITATION IMPACT: Baths in thermal waters, especially those in sulfurous waters, are effective in reducing pain and improving physical function in patients with knee osteoarthritis. PMID- 26899039 TI - Prevalence and management of patients with outpatient commitment in the mental health services. AB - Background People with mental health problems are mostly treated within the community. The law allows for the use of compulsory mental health care both in hospital and in the community. Various forms of outpatient commitment (OC) have been adopted in much European legislation. To be subjected to OC is a serious intervention in a person's life. Aim The purpose of this study is to gain knowledge about patients who undergo OC. The study explores the incidence and prevalence of OC in a geographical area, the central characteristics of the sample, and how the framework for follow-up treatment for patients to resolve OC works. Methods The data were collected from a review of electronic patient records. The statistical methods used in this study were descriptive analysis, with frequency analysis and cross-tabulation analysis. Results The main finding in the present study is that the use of OC has increased. An important finding is that most of the patients have a decision made for OC that is justified by the treatment criterion. The present study shows that there is insufficient documentation on statutory responsibilities for follow-up treatment of patients with an OC. Conclusions This study shows that the use of OC has increased. It should be considered whether implemented measures to reduce the use of coercion have the desired effect. PMID- 26899122 TI - [Correlation of optical coherence tomographic and fundus autofluorescence in Stargardt disease]. PMID- 26899123 TI - [Severe corneal melting long after introduction of an intracorneal ring for keratoconus]. PMID- 26899124 TI - Effects of astaxanthin and emodin on the growth, stress resistance and disease resistance of yellow catfish (Pelteobagrus fulvidraco). AB - Yellow catfish (Pelteobagrus fulvidraco) has become a commercially important fish species in China and eastern Asia. High-density aquaculture has led to congestion and excessive stress and contributed to bacterial infection outbreaks that have caused high mortality. We investigated the effects of dietary supplementation with astaxanthin and emodin alone and in combination on the growth and stress resistance of yellow catfish. After 60 days of feeding, each group of fish (control, astaxanthin, emodin, and astaxanthin plus emodin (combination) groups) was exposed to acute crowding stress for 24 h, and a subsample of fish from the four groups was challenged with the bacterial septicemia pathogen Proteus mirabilis after the end of the crowding stress experiment. Compared with the control, the astaxanthin and emodin groups showed increases in serum total protein (TP), hepatic superoxide dismutase (SOD) activity and hepatic heat shock proteins 70 (HSP70) mRNA levels at 12 and 24 h after the initiation of crowding stress. The combination group exhibited increases in alanine aminotransferase (ALT) activity, aspartate aminotransferase (AST) activity, serum TP, hepatic SOD activity and hepatic HSP70 mRNA levels within 24 h after the initiation of crowding stress. However, decreases relative to the control were observed in the serum cortisol and glucose contents in the three treatment groups at 12 and 24 h after the initiation of crowding stress, in ALT and AST activity in the astaxanthin and emodin group at 24 h after the initiation of crowding stress, and in the serum lysozyme activity, serum alkaline phosphatase (ALP) activity, and hepatic catalase (CAT) and malondialdehyde (MDA) activity in the combination group at 24 h after the initiation of crowding stress. Additionally, the cumulative mortality after P. mirabilis infection was lower in all three treatment groups (57.00%-70.33%) than in the control (77.67%). Dietary supplementation with astaxanthin and emodin decreased the specific growth rate (SGR) and weight gain (WG) of healthy yellow catfish, although significant differences in mortality were not observed. These results indicate that dietary supplementation with 80 mg/kg astaxanthin and 150 mg/kg emodin can improve the anti-oxidative capabilities, hepatic HSP70 levels, and resistance to acute crowding stress of yellow catfish. Finally, an appropriate strategy for enhance yellow catfish stress resistance and disease resistance is proposed. PMID- 26899125 TI - Dietary supplementation of Zeolite on growth performance, immunological role, and disease resistance in Channa striatus against Aphanomyces invadans. AB - Epizootic Ulcerative Syndrome (EUS) caused by Aphanomyces invadans which is a primary fungal parasitic pathogen, inflicts serious economic loss in tropical freshwater fish including snakehead murrel, Channa striatus. In the present study with an aim to circumvent the adverse effects of the traditional measures in graded levels (2%, 4%, and 6%) of Zeolite enriched diet on growth performance, hematology, immunological response, and disease resistance in C. striatus against A. invadans is reported. The final weight (FW), specific growth rate (SGR), feed conversion ratio (FCR), protein efficiency ratio (PER), and average daily gain (ADG) were significantly high in infected fish fed with 4% or 6% Zeolite incorporated diets on 4th week. The maximum survival rates (SR) of 96% and 98% were observed when fed with 2% or 4% diets on 4th week. Similarly, the white blood cell (WBC), red blood cell (RBC), hematocrit (Hct), mean corpuscular volume (MCV), and mean corpuscular haemoglobin concentration (MCHC) were significantly high when fed with any Zeolite enriched diet. However, the haemoglobin (Hb) and mean corpuscular haemoglobin (MCH) were significantly high with 4% and 6% Zeolite diets. The total protein and globulin were significantly high with 4% and 6% diets; the albumin, glucose, cholesterol, and triglyceride were significantly elevated with any enriched diet. The 4% and 6% Zeolite diets significantly enhanced the phagocytic activity on 2nd week but the 2% diet could increase it on 4th week. The respiratory burst (RB) activity, complement activity, and lymphocyte proliferation level were significantly enhanced with 4% and 6% Zeolite diets on weeks 1 and 2 while with 2% diet on 4th week. All enriched diets significantly increased the lysozyme activity during the experimental period. Superoxide anion (SOA) production significantly enhanced with 6% diet on weeks 1 and 2 whereas with 2% diet on week 4. Lower cumulative mortality of 10% and 15% was found with 4% and 6% Zeolite diets whereas a higher mortality (20%) was observed with 2% diet. The present study suggests that dietary supplementation with 4% or 6% Zeolite significantly increase growth performance, hemato biochemical changes, immunological response, and disease resistance in C. striatus against A. invadans. PMID- 26899126 TI - Tryptophan Catabolites and Their Impact on Multiple Sclerosis Progression. AB - Accumulating evidence demonstrates involvement of tryptophan metabolites and in particular activation of the kynurenine pathway (KP) in neurocognitive disorders under CNS inflammatory conditions. The KP is involved in several brain-associated disorders including Parkinson's disease, AIDS dementia, Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis, schizophrenia, and brain tumors. Our review is an attempt to address any relevant association between dysregulation of KP and multiple sclerosis (MS), an inflammatory CNS disorder that ultimately leads to demyelinated brain areas and severe neurological deficits. Modulation of KP is a new topic for the field of MS and warrants further research. The availability of potential KP modulators approved for MS may shed some light into the therapeutic potential of KP antagonists for the treatment of MS patients. PMID- 26899127 TI - Influence of polymer molecular weight on in vitro dissolution behavior and in vivo performance of celecoxib:PVP amorphous solid dispersions. AB - In this study, the influence of the molecular weight of polyvinylpyrrolidone (PVP) on the non-sink in vitro dissolution and in vivo performance of celecoxib (CCX):PVP amorphous solid dispersions were investigated. The dissolution rate of CCX from the amorphous solid dispersions increased with decreasing PVP molecular weight and crystallization inhibition was increased with increasing molecular weight of PVP, but reached a maximum for PVP K30. This suggested that the crystallization inhibition was not proportional with molecular weight of the polymer, but rather there was an optimal molecular weight where the crystallization inhibition was strongest. Consistent with the findings from the non-sink in vitro dissolution tests, the amorphous solid dispersions with the highest molecular weight PVPs (K30 and K60) resulted in significantly higher in vivo bioavailability (AUC0-24h) compared with pure amorphous and crystalline CCX. A linear relationship between the in vitro and in vivo parameter AUC0-24h indicated that the simple non-sink in vitro dissolution method used in this study could be used to predict the in vivo performance of amorphous solid dispersion with good precision, which enabled a ranking between the different formulations. In conclusion, the findings of this study demonstrated that the in vitro and in vivo performance of CCX:PVP amorphous solid dispersions were significantly controlled by the molecular weight of the polymer. PMID- 26899128 TI - Exploring family experiences of nursing aspects of end-of-life care in the ICU: A qualitative study. AB - OBJECTIVES: The aim of this study was to examine the experience(s) of family with the nursing aspects of End-of-life care in the intensive care unit after a decision to end life-sustaining treatment, and to describe what nursing care was most appreciated and what was lacking. METHOD: A phenomenological approach including inductive thematic analysis was used. Twenty-six family members of deceased critically ill-patients were interviewed within two months after the patient's death about their experiences with nursing aspects of end-of-life care in the intensive care unit. FINDINGS: Most family members experienced nursing contribution to end-of-life care of the patient and themselves, especially supportive care. Families mentioned the following topics: Communication between intensive care nurses, critically ill patients and family; Nursing care for critically ill patients; Nursing care for families of critically ill patients; Pre-conditions. Families appreciated that intensive care nurses were available at any time and willing to answer questions. But care was lacking because families had for example, a sense of responsibility for obtaining information, they had problems to understand their role in the decision-making process, and were not invited by nurses to participate in the care. CONCLUSIONS: Most family appreciated the nursing EOLC they received, specifically the nursing care given to the patient and themselves. Some topics needed more attention, like information and support for the family. PMID- 26899131 TI - Serum lipid profile in oral squamous cell carcinoma: alterations and association with some clinicopathological parameters and tobacco use. AB - Hypocholesterolemia has been observed in patients with cancers of various organs; however the potential role of alterations in serum lipid profile in oral cancer remains controversial. Hence, this study aimed to evaluate the serum lipid profile in oral squamous cell carcinoma (OSCC) and its prognostic significance. Ninety untreated OSCC patients, who reported to the craniofacial unit for treatment between 2011 and 2014, were identified to obtain clinicopathological data and preoperative blood investigations including lipid profile. The fasting blood lipid profile, including total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL), and low density lipoprotein (LDL), was evaluated using a fully automated biochemistry analyser. Data were analyzed statistically using the Student's t-test, analysis of variance, and post hoc tests. Statistically significant decreases in serum TC, HDL, and LDL levels were observed in OSCC patients as compared to healthy controls (P<0.05). There was no statistically significant difference in mean lipid profile values in terms of stage, grade, or lymph node metastasis. This study identified changes in lipid profiles in OSCC. The results suggest that during the development and progression of OSCC, levels of serum lipids are decreased. A review of the literature confirmed that OSCC patients exhibit aberrant serum lipid patterns. PMID- 26899129 TI - Role of TrkB in the anxiolytic-like and antidepressant-like effects of vagal nerve stimulation: Comparison with desipramine. AB - A current hypothesis regarding the mechanism of antidepressant (AD) action suggests the involvement of brain-derived neurotrophic factor (BDNF). Consistent with this hypothesis, the receptor for BDNF (and neurotrophin 4/5 (NT-4/5)), Tropomyosin-related kinase B (TrkB), is activated in rodents by treatment with classical AD drugs. Vagal nerve stimulation (VNS), a therapy for treatment resistant depression (TRD), also activates TrkB in rodents. However, the role of this receptor in the therapeutic effects of VNS is unclear. In the current study, the involvement of TrkB in the effects of VNS was investigated in rats using its inhibitor, K252a. Anxiolytic-like and AD-like effects were analyzed using the novelty suppressed feeding test (NSFT) and forced swim test (FST), respectively. K252a blocked the anxiolytic-like effect of chronic VNS treatment and the AD-like effect of acute VNS treatment. By contrast, blocking TrkB did not prevent either the anxiolytic-like or AD-like effect of chronic treatment with desipramine (DMI), a selective noradrenergic reuptake inhibitor; it did, however, block the acute effect of DMI in the FST. To examine whether the activation of TrkB caused by either VNS or DMI is ligand-dependent, use was made of TrkB-Fc, a molecular scavenger for ligands of TrkB. Intraventricular administration of TrkB-Fc blocked the acute activation of TrkB induced by either treatment, indicating that treatment-induced activation of this receptor is ligand-dependent. The behavioral results highlight differences in the involvement of TrkB in the chronic effects of an AD drug and a stimulation therapy as well as its role in acute versus chronic effects of DMI. PMID- 26899130 TI - Ion Channel Diseases: an Update for 2016. AB - OPINION STATEMENT: Ion channelopathies are a frequent cause of sudden cardiac death (SCD) in patients with structurally normal hearts. These are generally Mendelian inherited electrical disorders with variable penetrance and expressivity. The ability to predict the development of life threatening arrhythmias in these patients is challenging. This chapter will present an update on the genetics, the role of genetic testing, and management of the inherited cardiac channelopathies with a focus on the relatively more common syndromes associated with an increased risk of SCD. PMID- 26899133 TI - Coffee, caffeine, and sleep: A systematic review of epidemiological studies and randomized controlled trials. AB - Caffeine is the most widely consumed psychoactive substance in the world. It is readily available in coffee and other foods and beverages, and is used to mitigate sleepiness, enhance performance, and treat apnea in premature infants. This review systematically explores evidence from epidemiological studies and randomized controlled trials as to whether coffee and caffeine have deleterious effects on sleep. Caffeine typically prolonged sleep latency, reduced total sleep time and sleep efficiency, and worsened perceived sleep quality. Slow-wave sleep and electroencephalographic (EEG) slow-wave activity were typically reduced, whereas stage-1, wakefulness, and arousals were increased. Dose- and timing response relationships were established. The sleep of older adults may be more sensitive to caffeine compared to younger adults. Pronounced individual differences are also present in young people, and genetic studies isolated functional polymorphisms of genes implicated in adenosine neurotransmission and metabolism contributing to individual sensitivity to sleep disruption by caffeine. Most studies were conducted in male adults of Western countries, which limits the generalizability of the findings. Given the importance of good sleep for general health and functioning, longitudinal investigations aimed at establishing possible causal relationships among coffee- and caffeine-induced changes in sleep quality and health development are warranted. PMID- 26899132 TI - Intramuscular fat and physical performance at the Framingham Heart Study. AB - Intramuscular fat may mediate associations between obesity and physical disability. We examined the associations between muscle attenuation, a proxy for intramuscular fat, and physical function. Paraspinous muscle computed tomography attenuation was obtained on a Framingham Heart Study subgroup (n = 1152, 56 % women, mean age 66 years). Regressions modeled cross-sectional associations between muscle attenuation and mobility disability, grip strength, and walking speed with standard covariates; models additionally adjusted for body mass index (BMI) and visceral adipose tissue (VAT). Separate models investigated associations between VAT and subcutaneous adipose tissue (SAT) and physical function. Per 1 standard deviation decrement in muscle attenuation (i.e., more muscle fat), we observed 1.29 (95 % CI = 1.11, 1.50; p = 0.0009) increased odds of walking speed <=1 m/s in women and men. This persisted after separate BMI and VAT adjustments (p < 0.02). In men, there was a 1.29 kg (95 % CI = 0.57, 2.01; p = 0.0005) decrement in grip strength, which persisted after BMI and VAT adjustments (p <= 0.0004). For VAT and SAT, similar associations were not observed. Intramuscular fat is associated with increased odds of walking speed <=1 m/s in both sexes and lower grip strength in men. There were no similar associations for VAT and SAT, highlighting the specificity of intramuscular fat in association with physical function. PMID- 26899134 TI - Intraspecific and heteroplasmic variations, gene losses and inversions in the chloroplast genome of Astragalus membranaceus. AB - Astragalus membranaceus is an important medicinal plant in Asia. Several of its varieties have been used interchangeably as raw materials for commercial production. High resolution genetic markers are in urgent need to distinguish these varieties. Here, we sequenced and analyzed the chloroplast genome of A. membranaceus (Fisch.) Bunge var. mongholicus (Bunge) P.K. Hsiao using the next generation DNA sequencing technology. The genome was assembled using Abyss and then subjected to gene prediction using CPGAVAS and repeat analysis using MISA, Tandem Repeats Finder, and REPuter. Finally, the genome was subjected phylogenetic and comparative genomic analyses. The complete genome is 123,582 bp long, containing only one copy of the inverted repeat. Gene prediction revealed 110 genes encoding 76 proteins, 30 tRNAs, and four rRNAs. Five intra-specific hypermutation loci were identified, three of which are heteroplasmic. Furthermore, three gene losses and two large inversions were identified. Comparative genomic analyses demonstrated the dynamic nature of the Papilionoideae chloroplast genomes, which showed occurrence of numerous hypermutation loci, frequent gene losses, and fragment inversions. Results obtained herein elucidate the complex evolutionary history of chloroplast genomes and have laid the foundation for the identification of genetic markers to distinguish A. membranaceus varieties. PMID- 26899136 TI - Multidimensional assessment of impulsivity in schizophrenia, bipolar disorder, and major depressive disorder: testing for shared endophenotypes. AB - BACKGROUND: Impulsivity is associated with bipolar disorder as a clinical feature during and between manic episodes and is considered a potential endophenotype for the disorder. Schizophrenia and major depressive disorder share substantial genetic overlap with bipolar disorder, and these two disorders have also been associated with elevations in impulsivity. However, little is known about the degree of overlap among these disorders in discrete subfacets of impulsivity and whether any overlap is purely phenotypic or due to shared genetic diathesis. METHOD: We focused on five subfacets of impulsivity: self-reported attentional, motor, and non-planning impulsivity, self-reported sensation seeking, and a behavioral measure of motor inhibition (stop signal reaction time; SSRT). We examined these facets within and across disorder proband and co-twin groups, modeled heritability, and tested for endophenotypic patterning in a sample of twin pairs recruited from the Swedish Twin Registry (N = 420). RESULTS: We found evidence of moderate to high levels of heritability for all five subfacets. All three proband groups and their unaffected co-twins showed elevations on attentional, motor, and non-planning impulsivity. Schizophrenia probands (but not their co-twins) showed significantly lower sensation seeking, and schizophrenia and bipolar disorder probands (but not in their co-twins) had significantly longer SSRTs, compared with healthy controls and the other groups. CONCLUSIONS: Attentional, motor, and non-planning impulsivity emerged as potential shared endophenotypes for the three disorders, whereas sensation seeking and SSRT were associated with phenotypic affection but not genetic loading for these disorders. PMID- 26899135 TI - Virtual stenting workflow with vessel-specific initialization and adaptive expansion for neurovascular stents and flow diverters. AB - Endovascular intervention using traditional neurovascular stents and densely braided flow diverters (FDs) have become the preferred treatment strategies for traditionally challenging intracranial aneurysms. Modeling stent and FD deployment in patient-specific aneurysms and its flow modification results prior to the actual intervention can potentially predict the patient outcome and treatment optimization. We present a clinically focused, streamlined virtual stenting workflow that efficiently simulates stent and FD treatment in patient specific aneurysms based on expanding a simplex mesh structure. The simplex mesh is generated using an innovative vessel-specific initialization technique, which uses the patient's parent artery diameter to identify the initial position of the simplex mesh inside the artery. A novel adaptive expansion algorithm enables the acceleration of deployment process by adjusting the expansion forces based on the distance of the simplex mesh from the parent vessel. The virtual stenting workflow was tested by modeling the treatment of two patient-specific aneurysms using the Enterprise stent and the Pipeline Embolization Device (commercial FD). Both devices were deployed in the aneurysm models in a few seconds. Computational fluid dynamics analyses of pre- and post-treatment aneurysmal hemodynamics show flow reduction in the aneurysmal sac in treated aneurysms, with the FD diverting more flow than the Enterprise stent. The test results show that this workflow can rapidly simulate clinical deployment of stents and FDs, hence paving the way for its future clinical implementation. PMID- 26899137 TI - Minilaparoscopic cholecystectomy a one year record. AB - PURPOSE: Our study is to demonstrate the feasibility and the safety of the Minilaparoscopic Cholecystectomy. MATERIAL OF STUDY: During one year period 12 patients underwent 5mm Laparoscopic Cholecystectomy and 102 patientunderwent Mini laparoscopic Cholecystectomy. In this study the exclusion criteria for surgery have been analyzed as well as the technical difficulties, the operation time, the duration of hospital stay, the post-surgery pain, the complications and the aesthetic results RESULTS: The operation time was 3 minutes longer for Mini laparoscopic Cholecystectomy, the hospital stay was shorter in Mini-laparoscopic group. Patients that underwent 5mm Laparoscopic Cholecystectomy required a longer analgesic therapy. Complications occurred during the study were not related to the method. The aesthetic results were better in Minilaparoscopic Cholecystectomy due to lower scars length. Only in two cases we converted the planned Mini laparoscopic Cholecystectomy in 5mm Laparoscopic Cholecystectomy. DISCUSSION: All the patients submitted to Mini-laparoscopic Cholecystectomy and 5mm Laparoscopic Cholecystectomy had the same therapeutic result. The Mini-laparoscopic Cholecystectomy gave advantages on post-surgery pain and recovery time. CONCLUSIONS: In our experience the Mini-laparoscopic Cholecystectomy is a safe method that guarantees the same clinical results of conventional Laparoscopic Cholecystectomy. It shows some technical difficulties, but yet this surgery is to be recommended to expert surgeons. KEY WORDS: Gallbladder Polyps, Gallstone Disease, Mini-laparoscopic Cholecistecomy. PMID- 26899138 TI - Profile of Steroid Receptors and Increased Aromatase Immunoexpression in Canine Inflammatory Mammary Cancer as a Potential Therapeutic Target. AB - Canine inflammatory mammary cancer (IMC) has been proposed as a model for the study of human inflammatory breast cancer (IBC). The aims of this study were to compare the immunohistochemical expression of aromatase (Arom) and several hormone receptors [estrogen receptor alpha (ERalpha), estrogen receptor beta (ERbeta), progesterone receptor (PR) and androgen receptor (AR)], in 21 IMC cases vs 19 non-IMC; and to study the possible effect of letrozole on canine IMC and human inflammatory breast cancer (IBC) in vitro using IPC-366 and SUM-149 cell lines. Significant elevations of the means of Arom Total Score (TS), ERbeta TS and PR TS were found in the IMC group (p = 0.025, p = 0.038 and p = 0.037, respectively). Secondary IMC tumours expressed higher levels of Arom than primary IMC (p = 0.029). Non-IMC PR- tumours contained higher levels of Arom than non-IMC PR+ tumours (p = 0.007). After the addition of letrozole, the number of IMC and IBC cells dropped drastically. The overexpression of Arom found and the results obtained in vitro further support canine IMC as a model for the study of IBC and future approaches to the treatment of dogs with mammary cancer, and especially IMC, using Arom inhibitors. PMID- 26899139 TI - The role of nano-perovskite in the negligible thorium release in seawater from Greek bauxite residue (red mud). AB - We present new data about the chemical and structural characteristics of bauxite residue (BR) from Greek Al industry, using a combination of microscopic, analytical, and spectroscopic techniques. SEM-EDS indicated a homogeneous dominant "Al-Fe-Ca-Ti-Si-Na-Cr matrix", appearing at the microscale. The bulk chemical analyses showed considerable levels of Th (111 MUg g(-1)), along with minor U (15 MUg g(-1)), which are responsible for radioactivity (355 and 133 Bq kg(-1) for (232)Th and (238)U, respectively) with a total dose rate of 295 nGy h( 1). Leaching experiments, in conjunction with SF-ICP-MS, using Mediterranean seawater from Greece, indicated significant release of V, depending on S/L ratio, and negligible release of Th at least after 12 months leaching. STEM-EDS/EELS &HR STEM-HAADF study of the leached BR at the nanoscale revealed that the significant immobility of Th(4+) is due to its incorporation into an insoluble perovskite type phase with major composition of Ca(0.8)Na(0.2)TiO3 and crystallites observed in nanoscale. The Th L(III)-edge EXAFS spectra demonstrated that Th(4+) ions, which are hosted in this novel nano-perovskite of BR, occupy Ca(2+) sites, rather than Ti(4+) sites. That is most likely the reason of no Th release in Mediterranean seawater. PMID- 26899140 TI - [Interventions to optimize pharmacologic treatment in hospitalized older adults: a systematic review]. AB - OBJECTIVE: To summarise the evidence on interventions aimed at optimising the drug treatment of hospitalised elderly patients. MATERIAL AND METHODS: We conducted a search in the main medical literature databases, selecting prospective studies of hospitalised patients older than 65 years who underwent interventions aimed at optimising drug treatment, decreasing polypharmacy and improving the medication appropriateness, health outcomes and exploitation of the healthcare system. RESULTS: We selected 18 studies whose interventions consisted of medication reviews, detection of predefined drugs as potentially inappropriate for the elderly, counselling from a specialised geriatric team, the use of a computer support system for prescriptions and specific training for the nursing team. Up to 14 studies assessed the medication appropriateness, 13 of which showed an improvement in one or more of the parameters. Seven studies measured the impact of the intervention on polypharmacy, but only one improved the outcomes compared with the control. Seven other studies analysed mortality, but none of them showed a reduction in that rate. Only 1 of 6 studies showed a reduction in the number of hospital readmissions, and 1 of 4 studies showed a reduction in the number of emergency department visits. CONCLUSIONS: Despite the heterogeneity of the analysed interventions and variables, we obtained better results in the process variables (especially in medication appropriateness) than in those that measured health outcomes, which had greater variability. PMID- 26899141 TI - Erratum to: The advantages of tomosynthesis for evaluating bisphosphonate-related atypical femur fractures compared to radiography. PMID- 26899142 TI - Outcome and Safety of Sorafenib in Metastatic Renal Cell Carcinoma Dialysis Patients: A Systematic Review. AB - Few data are available about sorafenib use in patients with metastatic renal cell carcinoma (mRCC) undergoing hemodialysis. No systematic review has been previously performed about this issue. The objective of the present review is to investigate pharmacokinetics and clinical outcomes of sorafenib in mRCC patients undergoing hemodialysis. According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, all the literature about mRCC dialysis patients receiving sorafenib, published from January 1946 to August 2015, was evaluated. Applying inclusion/exclusion criteria, 11 articles were selected for the analysis; 1 patient from our department was also included. The investigated outcomes were pharmacokinetics, toxicity, response rate, progression free survival, and overall survival where available. A total of 36 patients were included. Median treatment duration was 6.0 months on overall population; median progression-free survival was 6.3 months (calculated on 19 patients); response rate was 22% (on 29 patients); median overall survival was 14.9 months (on 28 patients). Of note, 24 patients started sorafenib at reduced dose; 6 of 36 patients (17%) required dose reduction due to adverse events (AEs). Sorafenib treatment was discontinued in 7 patients (19%) because of AEs. Most of AEs were Grade 1-2; severe toxicities (Grade 4-5) included G4 anemia (1 case), G4 hypertension (1 case), G4 cerebellar hemorrhage (1 patient), and a case of G5 subarachnoid hemorrhage. This review confirmed the efficacy of sorafenib treatment in mRCC patients receiving hemodialysis. Nevertheless, drug toxicity seems to be increased in these patients, despite the initiation of therapy at reduced doses; therefore, sorafenib should be used with caution in dialysis patients. PMID- 26899144 TI - Model building to facilitate understanding of holliday junction and heteroduplex formation, and holliday junction resolution. AB - Students frequently expressed difficulty in understanding the molecular mechanisms involved in chromosomal recombination. Therefore, we explored alternative methods for presenting the two concepts of the double-strand break model: Holliday junction and heteroduplex formation, and Holliday junction resolution. In addition to a lecture and computer-animated video, we included a model building activity using pipe cleaners. Biotechnology undergraduates (n = 108) used the model to simulate Holliday junction and heteroduplex formation, and Holliday junction resolution. Based on student perception, an average of 12.85 and 78.35% students claimed that they completely and partially understood the two concepts, respectively. A test conducted to ascertain their understanding about the two concepts showed that 66.1% of the students provided the correct response to the three multiple choice questions. A majority of the 108 students attributed the inclusion of model building to their better understanding of Holliday junction and heteroduplex formation, and Holliday junction resolution. This underlines the importance of incorporating model building, particularly in concepts that require spatial visualization. (c) 2016 by The International Union of Biochemistry and Molecular Biology, 44(4):381-390, 2016. PMID- 26899145 TI - The shear band controlled deformation in metallic glass: a perspective from fracture. AB - Different from the homogenous deformation in conventional crystalline alloys, metallic glasses and other work-softening materials deform discontinuously by localized plastic strain in shear bands. Here by three-point bending test on a typical ductile Pd-Cu-Si metallic glass, we found that the plastic deformed region during fracture didn't follow the yielding stress distribution as the conventional material mechanics expected. We speculated that such special behavior was because the shear bands in metallic glasses could propagate easily along local shear stress direction once nucleated. Based on a 3D notch tip stress field simulation, we considered a new fracture process in a framework of multiple shear band deformation mechanism instead of conventional materials mechanics, and successfully reproduced the as-observed complicate shear band morphologies. This work clarifies many common misunderstandings on metallic glasses fracture, and might also provide a new insight to the shear band controlled deformation. It suggests that the deformation of metallic glasses is sensitive to local stress condition, and therefore their mechanical properties would depend on not only the material, but also other external factors on stress condition. We hope that start from this work, new methods, criteria, or definitions could be proposed to further study these work-softening materials, especially for metallic glasses. PMID- 26899143 TI - The modification of Gat1p in nitrogen catabolite repression to enhance non preferred nitrogen utilization in Saccharomyces cerevisiae. AB - In Saccharomyces cerevisiae, when preferred nitrogen sources are present, the metabolism of non-preferred nitrogen is repressed. Previous work showed that this metabolic regulation is primarily controlled by nitrogen catabolite repression (NCR) related regulators. Among these regulators, two positive regulators (Gln3p and Gat1p) could be phosphorylated and sequestered in the cytoplasm leading to the transcription of non-preferred nitrogen metabolic genes being repressed. The nuclear localization signals (NLSs) and nuclear localization regulatory signals (NLRSs) in Gln3p and Gat1p play essential roles in the regulation of their localization in cells. However, compared with Gln3p, the information of NLS and NLRS for Gat1p remains unknown. In this study, residues 348-375 and 366-510 were identified as the NLS and NLRS of Gat1p firstly. In addition, the modifications of Gat1p (mutations on the NLS and truncation on the NLRS) were attempted to enhance the transcription of non-preferred nitrogen metabolic genes. Quantitative real-time PCR showed that the transcriptional levels of 15 non-preferred nitrogen metabolic genes increased. Furthermore, during the shaking-flask culture tests, the utilization of urea, proline and allantoine was significantly increased. Based on these results, the genetic engineering on Gat1p has a great potential in enhancing non-preferred nitrogen metabolism in S. cerevisiae. PMID- 26899146 TI - Emergence of catalytic bioscavengers against organophosphorus agents. AB - Bioscavengers are an effective alternative approach for pre- and post-exposure treatments of nerve agent (NA) poisoning. Bioscavengers are natural or recombinant enzymes, reactive proteins, and antibodies that neutralize NAs before they reach their physiological targets. They are administered by injection (protein or gene delivery vector) and react with NAs in the bloodstream. Other ways of delivery can be used: inhalation for pulmonary delivery, topical creams for skin protection, etc. Operational bioscavengers must be producible at low cost, not susceptible to induce immune response and adverse effects, and stable in the bloodstream, upon storage, and under field conditions. First generation bioscavengers, cholinesterases and carboxylesterases, are stoichiometric bioscavengers. However, stoichiometric neutralization of NAs needs administration of huge doses of costly biopharmaceuticals. Second generation bioscavengers are catalytic bioscavengers. These are capable of detoxifying organophosphates regeneratively. By virtue of high turnover, much lower doses are needed for rapid neutralization of toxicants. The most promising catalytic bioscavengers are evolved mutants of phosphotriesterases (bacterial enzymes, mammalian paraoxonases), displaying enantiomeric preference for toxic NA isomers. However, engineering of cholinesterases, carboxylesterases, prolidases and other enzymes, e.g. phosphotriesterases-lactonases from extremophiles is of interest. In particular, association of cholinesterase mutants (not susceptible to age after phosphylation) with fast-reactivating oximes leads to pseudocatalytic bioscavengers. Thus, catalytic and pseudocatalytic bioscavengers are an improvement of bioscavenger-based medical countermeasures in terms of efficacy and cost. PMID- 26899147 TI - Endovascular management of renal transplant dysfunction secondary to hemodynamic effects related to ipsilateral femoral arteriovenous graft. AB - Hemodialysis access options become complex in long-term treatment for patients with renal disease, while awaiting renal transplantation (RT). Once upper extremity sites are exhausted, lower extremities are used. RT is preferably in the contralateral iliac fossa, rarely ipsilateral. In current literature, RT dysfunction secondary to the hemodynamic effects of an ipsilateral femoral arteriovenous graft (AVG) has been rarely described. To our knowledge, AVG ligation is the only published technique for hemodynamic correction of an ipsilateral AVG. We present a simple, potentially reversible endovascular approach to manage the hemodynamic effects of an AVG, without potentially permanently losing future AVG access. PMID- 26899148 TI - Volume change of segments II and III of the liver after gastrectomy in patients with gastric cancer. AB - PURPOSE: We aimed to evaluate the relationship between gastrectomy and the volume of liver segments II and III in patients with gastric cancer. METHODS: Computed tomography images of 54 patients who underwent curative gastrectomy for gastric adenocarcinoma were retrospectively evaluated by two blinded observers. Volumes of the total liver and segments II and III were measured. The difference between preoperative and postoperative volume measurements was compared. RESULTS: Total liver volumes measured by both observers in the preoperative and postoperative scans were similar (P > 0.05). High correlation was found between both observers (preoperative r=0.99; postoperative r=0.98). Total liver volumes showed a mean reduction of 13.4% after gastrectomy (P = 0.977). The mean volume of segments II and III showed similar decrease in measurements of both observers (38.4% vs. 36.4%, P = 0.363); the correlation between the observers were high (preoperative r=0.97, P < 0.001; postoperative r=0.99, P < 0.001). Volume decrease in the rest of the liver was not different between the observers (8.2% vs. 9.1%, P = 0.388). Time had poor correlation with volume change of segments II and III and the total liver for each observer (observer 1, rseg2/3=0.32, rtotal=0.13; observer 2, rseg2/3=0.37, rtotal=0.16). CONCLUSION: Segments II and III of the liver showed significant atrophy compared with the rest of the liver and the total liver after gastrectomy. Volume reduction had poor correlation with time. PMID- 26899149 TI - MRI in the differential diagnosis of primary architectural distortion detected by mammography. AB - PURPOSE: We aimed to evaluate the diagnostic accuracy of a combination of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and apparent diffusion coefficient (ADC) values in lesions that manifest with architectural distortion (AD) on mammography. METHODS: All full-field digital mammography (FFDM) images obtained between August 2010 and January 2013 were reviewed retrospectively, and 57 lesions showing AD were included in the study. Two independent radiologists reviewed all mammograms and MRI data and recorded lesion characteristics according to the BI-RADS lexicon. The gold standard was histopathologic results from biopsies or surgical excisions and results of the two-year follow-up. Receiver operating characteristic curve analysis was carried out to define the most effective threshold ADC value to differentiate malignant from benign breast lesions. We investigated the sensitivity and specificity of FFDM, DCE-MRI, FFDM+DCE-MRI, and DCE-MRI+ADC. RESULTS: Of the 57 lesions analyzed, 28 were malignant and 29 were benign. The most effective threshold for the normalized ADC (nADC) was 0.61 with 93.1% sensitivity and 75.0% specificity. The sensitivity and specificity of DCE-MRI combined with nADC was 92.9% and 79.3%, respectively. DCE MRI combined with nADC showed the highest specificity and equal sensitivity compared with other modalities, independent of the presentation of calcification. CONCLUSION: DCE-MRI combined with nADC values was more reliable than mammography in differentiating the nature of disease manifesting as primary AD on mammography. PMID- 26899150 TI - [Hereditary peroxisomal diseases]. AB - Peroxisomes are small intracellular organelles that catalyse key metabolic reactions such as the beta-oxidation of some straight-chain or branched-chain fatty acids and the alpha-oxidation of phytanic acid. These enzyme reactions produce hydrogen peroxide, which is subsequently neutralized by the peroxisomal catalase. Peroxisomes also metabolize glyoxylate to glycine, and catalyze the first steps of plasmalogen biosynthesis. There are more than a dozen inherited peroxisomal disorders in humans. These metabolic diseases are due to monogenic defects that affect either a single function (such as enzyme or a transporter) or more than two distinct functions because of the impairment of several aspects of peroxisome biogenesis. With the notable exception of X-linked adrenoleucodystrophy, these inborn disorders are transmitted as autosomal recessive traits. Their clinical presentation can be very heterogeneous, and include neonatal, infantile or adult forms. The present review describes the symptomatology of these genetic diseases, the underlying genetic and biochemical alterations, and summarizes their diagnostic approach. PMID- 26899151 TI - Development and Validation of a Near-Infrared Optical System for Tracking Surgical Instruments. AB - Surgical navigation systems can help doctors maximize the accuracy of surgeries, minimize operation durations, avoid mistakes, and improve the survival chances of patients. The tracking of device is an important component in surgical navigation systems. However, commercial surgical tracking devices are expensive, thus hindering the development of surgical navigation systems, particularly in developing countries. Therefore, an accurate and low-cost near-infrared optical tracking system is presented in this study for the real-time tracking of surgical tools and for measuring and displaying the positions of these tools relative to lesions and other targets inside a patient's body. A relative algorithm for the registration of surgical tools is also proposed in this paper to yield easy, safe, and precise tracking. Experiments are conducted to test the performance of the system. Results show that the mean square errors of the distances between the light-emitting points on the surgical tools are less than 0.3 mm, with the mean square error of distance between the tip and light-emitting points is less than 0.025 mm and that between two adjacent corner points is 0.2714 mm. PMID- 26899152 TI - Laser-assisted subepithelial keratectomy (LASEK) versus photorefractive keratectomy (PRK) for correction of myopia. AB - BACKGROUND: Myopia (near-sightedness or short-sightedness) is a condition in which the refractive power of the eye is greater than required. The most frequent complaint of people with myopia is blurred distance vision, which can be eliminated by conventional optical aids such as spectacles or contact lenses, or by refractive surgery procedures such as photorefractive keratectomy (PRK) and laser epithelial keratomileusis (LASEK). PRK uses laser to remove the corneal stroma. Similar to PRK, LASEK first creates an epithelial flap and then replaces it after ablating the corneal stroma. The relative benefits and harms of LASEK and PRK, as shown in different trials, warrant a systematic review. OBJECTIVES: The objective of this review is to compare LASEK versus PRK for correction of myopia by evaluating their efficacy and safety in terms of postoperative uncorrected visual acuity, residual refractive error, and associated complications. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision group Trials Register) (2015 Issue 12), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to December 2015), EMBASE (January 1980 to December 2015), Latin American and Caribbean Health Sciences (LILACS) (January 1982 to December 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 15 December 2015. We used the Science Citation Index and searched the reference lists of the included trials to identify relevant trials for this review. SELECTION CRITERIA: We included in this review randomized controlled trials (RCTs) comparing LASEK versus PRK for correction of myopia. Trial participants were 18 years of age or older and had no co-existing ocular or systemic diseases that might affect refractive status or wound healing. DATA COLLECTION AND ANALYSIS: Two review authors independently screened all reports and assessed the risk of bias of trials included in this review. We extracted data and summarized findings using risk ratios and mean differences. We used a random-effects model when we identified at least three trials, and we used a fixed-effect model when we found fewer than three trials. MAIN RESULTS: We included 11 RCTs with a total of 428 participants 18 years of age or older with low to moderate myopia. These trials were conducted in the Czech Republic, Brazil, Italy, Iran, China, Korea, Mexico, Turkey, USA, and UK. Investigators of 10 out of 11 trials randomly assigned one eye of each participant to be treated with LASEK and the other with PRK, but did not perform paired-eye (matched) analysis. Because of differences in outcome measures and follow-up times among the included trials, few trials contributed data for many of the outcomes we analyzed for this review. Overall, we judged RCTs to be at unclear risk of bias due to poor reporting; however, because of imprecision, inconsistency, and potential reporting bias, we graded the quality of the evidence from very low to moderate for outcomes assessed in this review.The proportion of eyes with uncorrected visual acuity of 20/20 or better at 12-month follow-up was comparable in LASEK and PRK groups (risk ratio (RR) 0.98, 95% confidence interval (95% CI) 0.92 to 1.05). Although the 95% CI suggests little to no difference in effect between groups, we judged the quality of the evidence to be low because only one trial reported this outcome (102 eyes). At 12 months post treatment, data from two trials suggest no difference or a possibly small effect in favor of PRK over LASEK for the proportion of eyes achieving +/- 0.50 D of target refraction (RR 0.93, 95% CI 00.84 to 1.03; 152 eyes; low-quality evidence). At 12 months post treatment, one trial reported that one of 51 eyes in the LASEK group lost one line or more best-spectacle corrected visual acuity compared with none of 51 eyes in the PRK group (RR 3.00, 95% CI 0.13 to 71.96; very low-quality evidence).Three trials reported adverse outcomes at 12 months of follow-up or longer. At 12 months post treatment, three trials reported corneal haze score; however, data were insufficient and were inconsistent among the trials, precluding meta analysis. One trial reported little or no difference in corneal haze scores between groups; another trial reported that corneal haze scores were lower in the LASEK group than in the PRK group; and one trial did not report analyzable data to estimate a treatment effect. At 24 months post treatment, one trial reported a lower, but clinically unimportant, difference in corneal haze score for LASEK compared with PRK (MD -0.22, 95% CI -0.30 to -0.14; 184 eyes; low-quality evidence). AUTHORS' CONCLUSIONS: Uncertainty surrounds differences in efficacy, accuracy, safety, and adverse effects between LASEK and PRK for eyes with low to moderate myopia. Future trials comparing LASEK versus PRK should follow reporting standards and follow correct analysis. Trial investigators should expand enrollment criteria to include participants with high myopia and should evaluate visual acuity, refraction, epithelial healing time, pain scores, and adverse events. PMID- 26899153 TI - Pancreatic neuroendocrine tumors in twelve baboons (Papio spp.). AB - BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) are rare in nonhuman primates and in humans. METHODS: Twenty-one PNETs from twelve female baboons (Papio spp.) from the Southwest National Primate Research Center were evaluated using histopathology and immunohistochemistry. RESULTS: Histologically, all tumors were benign and had neuroendocrine packeting. Immunohistochemical staining for synaptophysin and chromogranin was positive in all tumors evaluated (17/17). Insulin was positive in 16 of 21 tumors. Somatostatin was positive in 9 of 20 tumors. Multifocal staining for glucagon and pancreatic polypeptide was evident in a minority of tumors (6/20 and 2/17, respectively). Gastrin and vasoactive intestinal peptide were negative in all tumors evaluated. Nine tumors expressed more than one hormone marker. CONCLUSIONS: This is the first detailed pathologic study of pancreatic endocrine tumors in the baboon. The findings suggest that these tumors are generally benign and have similar morphologic and immunohistochemical features as those described in people, including the ability to express multiple hormones. PMID- 26899154 TI - Prospective evaluation of the Alere i Influenza A&B nucleic acid amplification versus Xpert Flu/RSV. AB - The rapid and accurate detection of influenza virus in respiratory specimens is required for optimal management of patients with acute respiratory infections. Because of the variability of the symptoms and the numerous other causes of influenza-like illness, the diagnosis of influenza cannot be made on the basis of clinical criteria alone. Thus, rapid influenza diagnostic tests have been developed such as the Alere i Influenza A&B isothermal nucleic acid assay. We prospectively evaluated the performance of the Alere i Influenza A&B assay in comparison with our routine Xpert Flu/RSV assay. Positive samples were subtyped according to the protocol from the National Influenza Center (Paris, France). A total of 96 respiratory nasal swab samples were analyzed: with both methods, 38 were positive and 56 were negative. Samples were prospectively collected from January 20 to April 8, 2015, from patient (86 adult and 10 pediatric patients) presenting with an influenza-like illness through the French influenza season. In comparison with the Xpert Flu/RSV assay, the overall sensitivity and specificity of the Alere i Influenza A&B assay were 95% and 100%, respectively. Our results indicate that the Alere i Influenza A&B assay has a good overall analytical performance and a high degree of concordance with the PCR-based Xpert Flu/RSV assay. The Alere i Influenza A&B isothermal nucleic acid amplification test is a powerful tool for influenza detection due to its high sensitivity and specificity as well as its ability to generate results within 15min. PMID- 26899155 TI - Vision, language and a protective mechanism towards psychosis. AB - The absence of co-occurrence of schizophrenia with congenital/early blindness (CB) has led to the claim that CB confers protection against schizophrenia. It has recently been shown that the protective effects are particularly reinforced in cases of CB of cortical origin, since cases of CB of peripheral origin and schizophrenia in fact exist. The present work shows that the protection extends to psychosis more broadly and describes the brain basis of the protective mechanism and its relation to the language faculty and the language areas of the brain. PMID- 26899156 TI - Involvement of spinal glutamate in nociceptive behavior induced by intrathecal administration of hemokinin-1 in mice. AB - The most recently identified tachykinin, hemokinin-1, was cloned from mouse bone marrow. While several studies indicated that hemokinin-1 is involved in pain and inflammation, the physiological functions of hemokinin-1 are not fully understood. Our previous research demonstrated that the intrathecal (i.t.) administration of hemokinin-1 (0.00625-1.6 nmol) dose-dependently induced nociceptive behaviors, consisting of scratching, biting and licking in mice, which are very similar with the nociceptive behaviors induced by the i.t. administration of substance P. Low-dose (0.0125 nmol) hemokinin-1-induced nociceptive behavior was inhibited by a specific NK1 receptor antagonist; however, high-dose (0.1 nmol) hemokinin-1-induced nociceptive behavior was not affected. In the present study, we found that the nociceptive behaviors induced by hemokinin-1 (0.1 nmol) were inhibited by the i.t. co-administration of MK-801 or D-APV, which are NMDA receptor antagonists. Moreover, we measured glutamate in the extracellular fluid of the mouse spinal cord using microdialysis. The i.t. administration of hemokinin-1 produced a significant increase in glutamate in the spinal cord, which was significantly reduced by co-administration with NMDA receptor antagonists. These results suggest that hemokinin-1-induced nociceptive behaviors may be mediated by the NMDA receptor in the spinal cord. PMID- 26899157 TI - Application of biological traits to further our understanding of the impacts of dredged material disposal on benthic assemblages. AB - While the effects of coastal disposal of dredged material on benthic assemblage structure have been well studied, our understanding of the mechanism of such responses, and their potential ecological implications, remain relatively unknown. Data from a licenced disposal site off the northeast coast of England are analysed to address this and improve our ability to make informed licencing decisions for this activity. Assemblages within the disposal site displayed reduced number of species and total invertebrate density, an altered assemblage taxonomic structure, and a shift towards a greater numerical dominance of less productive individuals. Following separate analyses of biological response and effect traits, a novel approach for marine benthic trait analysis, we identify the traits responsible (i.e. response traits) for the observed structural alterations. Furthermore, analysis of the effect traits revealed that the assemblages characterising the disposal site possess a greater bioturbative capability compared to those not directly impacted by disposal. PMID- 26899158 TI - Green Marine: An environmental program to establish sustainability in marine transportation. AB - European maritime companies have adopted programs to limit operational impacts on the environment. For maritime companies in North America, the Green Marine Environmental Program (GMEP) offers a framework to establish and reduce environmental footprints. Green Marine (GM) participants demonstrate annual improvements of specific environmental performance indicators (e.g., reductions in air pollution emissions) to maintain certification. Participants complete annual self-evaluations with results determining rankings for performance indicators on a 1-to-5 scale. Self-evaluations are independently verified every two years to ensure rigor and individual results are made publicly available annually to achieve transparency. GM benefits the marine industry across North America by encouraging sustainable development initiatives. GM's credibility is reflected through a diverse network of environmental groups and government agencies that endorse and help shape the program. Merits of this relatively new maritime certification (not previously described in the academic literature), are discussed. PMID- 26899161 TI - Tartary buckwheat flavonoids protect hepatic cells against high glucose-induced oxidative stress and insulin resistance via MAPK signaling pathways. AB - Oxidative stress plays a crucial role in chronic complication of diabetes. In this study, the protective effect of purified tartary buckwheat flavonoids (TBF) fraction against oxidative stress induced by a high-glucose challenge, which causes insulin resistance, was investigated on hepatic HepG2 cells. Oxidative status, phosphorylated mitogen-activated protein kinases (MAPKs), nuclear factor E2 related factor 2 (Nrf2) and p-(Ser307)-IRS-1 expression, and glucose uptake were evaluated. Results suggest that treatment of HepG2 cells with TBF alone improved glucose uptake and antioxidant enzymes, and activated Nrf2, and attenuated the IRS-1 Ser307 phosphorylation, and enhanced total levels of IRS-1. Furthermore, the high glucose-induced changes in antioxidant defences, Nrf2, p MAPKs, p-IRS1 Ser307, and IRS-1 levels, and glucose uptake were also significantly inhibited by pre-treatment with TBF. Interestingly, the selective MAPK inhibitors significantly enhanced the TBF-mediated protection by inducing changes in the redox status, glucose uptake, p-(Ser307) and total IRS-1 levels. This report firstly showed that TBF could recover the redox status of insulin resistant HepG2 cells, suggesting that TBF significantly protected the cells against high glucose-induced oxidative stress, and these beneficial effects of TBF on redox balance and insulin resistance were mediated by targeting MAPKs. PMID- 26899162 TI - Vitamin D decreases adipocyte lipid storage and increases NAD-SIRT1 pathway in 3T3-L1 adipocytes. AB - OBJECTIVE: Previous studies suggest that low vitamin D status is associated with obesity characterized by excess lipid storage in adipocytes. The aim of the present study was to determine the effects of the most hormonally active form of vitamin D 1,25-dihydroxyvitamin D [1,25(OH)2D] on adipocyte fat storage and lipid metabolism in mature 3T3-L1 cells. METHODS: Differentiated 3T3-L1 cells were treated with various concentrations of 1,25(OH)2D. 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide cell proliferation, intracellular lipid content, and basal and isoproterenol-stimulated lipolysis were measured to investigate the regulatory role of 1,25(OH)2D in adipocyte lipid metabolism. Reverse transcription polymerase chain reaction was performed to determine the effects of 1,25(OH)2D on adipogenesis-related markers, fatty acid oxidation-associated genes, and lipolytic enzymes. Sirtulin 1 (SIRT1) activity, nicotinamide adenine dinucleotide (NAD) and NADH were measured. RESULTS: 1,25(OH)2D treatment (24 h, 100 nmol/L) induced a decrease in intracellular fat accumulation and an increase of basal and isoproterenol-stimulated lipolysis without cell toxicity in adipocytes. Adipogenic gene levels were decreased. In contrast, mRNA levels of beta-oxidation-related genes, lipolytic enzymes, and vitamin D responsive gene were elevated by 1,25(OH)2D. Additionally, significant incremental changes in NAD levels, the ratio of NAD to NADH, and SIRT1 expression and activity were noted in 1,25(OH)2D-treated 3T3-L1 adipocytes. CONCLUSIONS: The observed potent inhibitory effect of 1,25(OH)2D on adipocyte fat storage in mature 3T3-L1 cells suggests that vitamin D might improve adipocyte metabolic function and protect against obesity. Increased NAD concentrations and SIRT1 activity may play a role in the mechanism of 1,25(OH)2D action. PMID- 26899163 TI - A glance at ... dietary emulsifiers, the human intestinal mucus and microbiome, and dietary fiber. PMID- 26899164 TI - Oxygen desaturation during night sleep affects decision-making in patients with obstructive sleep apnea. AB - This study assessed decision-making and its associations with executive functions and sleep-related factors in patients with obstructive sleep apnea. Thirty patients with untreated obstructive sleep apnea and 20 healthy age- and education matched controls performed the Iowa Gambling Task, a decision-making task under initial ambiguity, as well as an extensive neuropsychological test battery. Patients, but not controls, also underwent a detailed polysomnographic assessment. Results of group analyses showed that patients performed at the same level of controls on the Iowa Gambling Task. However, the proportion of risky performers was significantly higher in the patient group than in the control group. Decision-making did not correlate with executive functions and subjective ratings of sleepiness, whereas there was a significant positive correlation between advantageous performance on the Iowa Gambling Task and percentage of N2 sleep, minimal oxygen saturation, average oxygen saturation and time spent below 90% oxygen saturation level. Also, the minimal oxygen saturation accounted for 27% of variance in decision-making. In conclusion, this study shows that a subgroup of patients with obstructive sleep apnea may be at risk of disadvantageous decision-making under ambiguity. Among the sleep-related factors, oxygen saturation is a significant predictor of advantageous decision-making. PMID- 26899160 TI - Gene co-expression analysis identifies brain regions and cell types involved in migraine pathophysiology: a GWAS-based study using the Allen Human Brain Atlas. AB - Migraine is a common disabling neurovascular brain disorder typically characterised by attacks of severe headache and associated with autonomic and neurological symptoms. Migraine is caused by an interplay of genetic and environmental factors. Genome-wide association studies (GWAS) have identified over a dozen genetic loci associated with migraine. Here, we integrated migraine GWAS data with high-resolution spatial gene expression data of normal adult brains from the Allen Human Brain Atlas to identify specific brain regions and molecular pathways that are possibly involved in migraine pathophysiology. To this end, we used two complementary methods. In GWAS data from 23,285 migraine cases and 95,425 controls, we first studied modules of co-expressed genes that were calculated based on human brain expression data for enrichment of genes that showed association with migraine. Enrichment of a migraine GWAS signal was found for five modules that suggest involvement in migraine pathophysiology of: (i) neurotransmission, protein catabolism and mitochondria in the cortex; (ii) transcription regulation in the cortex and cerebellum; and (iii) oligodendrocytes and mitochondria in subcortical areas. Second, we used the high-confidence genes from the migraine GWAS as a basis to construct local migraine-related co expression gene networks. Signatures of all brain regions and pathways that were prominent in the first method also surfaced in the second method, thus providing support that these brain regions and pathways are indeed involved in migraine pathophysiology. PMID- 26899165 TI - Improved cardiac magnetic resonance thermometry and dosimetry for monitoring lesion formation during catheter ablation. AB - PURPOSE: A new real-time MR-thermometry pipeline was developed to measure multiple temperature images per heartbeat with 1.6*1.6*3 mm3 spatial resolution. The method was evaluated on 10 healthy volunteers and during radiofrequency ablation (RFA) in sheep. METHODS: Multislice, electrocardiogram-triggered, echo planar imaging was combined with parallel imaging, under free breathing conditions. In-plane respiratory motion was corrected on magnitude images by an optical flow algorithm. Motion-related susceptibility artifacts were compensated on phase images by an algorithm based on Principal Component Analysis. Correction of phase drift and temporal filter were included in the pipeline implemented in the Gadgetron framework. Contact electrograms were recorded simultaneously with MR thermometry by an MR-compatible ablation catheter. RESULTS: The temporal standard deviation of temperature in the left ventricle remained below 2 degrees C on each volunteer. In sheep, focal heated regions near the catheter tip were observed on temperature images (maximal temperature increase of 38 degrees C) during RFA, with contact electrograms of acceptable quality. Thermal lesion dimensions at gross pathology were in agreement with those observed on thermal dose images. CONCLUSION: This fully automated MR thermometry pipeline (five images/heartbeat) provides direct assessment of lesion formation in the heart during catheter-based RFA, which may improve treatment of cardiac arrhythmia by ablation. Magn Reson Med 77:673-683, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 26899166 TI - Expression of CDc6 after acute spinal cord injury in adult rats. AB - The cell division cycle 6 (CDc6) protein has been primarily investigated as a component of the pre-replicative complex for the initiation of DNA replication. Some studies have shown that CDc6 played a critical role in the development of human carcinoma. However, the expression and roles of CDc6 in the central nervous system remain unknown. We have performed an acute spinal cord injury (SCI) model in adult rats and investigated the dynamic changes of CDc6 expression in spinal cord. Western blot have found that CDc6 protein levels first significantly increase, reach a peak at day 3, and then gradually return to normal level at day 14 after SCI. Double immunofluorescence staining showed that CDc6 immunoreactivity was found in neurons, astrocytes, and microglia. Additionally, colocalization of CDc6/active caspase-3 has been detected in neurons and colocalization of CDc6/proliferating cell nuclear antigen has been detected in astrocytes and microglial. In vitro, CDc6 depletion by short interfering RNA inhibits astrocyte proliferation and reduces cyclin A and cyclin D1 protein levels. CDc6 knockdown also decreases neuronal apoptosis. We speculate that CDc6 might play crucial roles in CNS pathophysiology after SCI. PMID- 26899168 TI - The construction of functional protein nanotubes by small molecule-induced self assembly of cricoid proteins. AB - A simple strategy has been developed to construct high-ordered protein nanotubes using electrostatic interactions and "zero-length" crosslinking induced by small molecular ethylenediamine. Furthermore, utilizing covalent crosslinking, we constructed stable nanoenzymes with multi-glutathione peroxidase (GPx) active centers on the surface of the nanotubes, which were anticipated to be ideal functional bionanomaterials. PMID- 26899167 TI - Pay Attention to the Overlooked Cryptic Diversity in Existing Barcoding Data: the Case of Mollusca with Character-Based DNA Barcoding. AB - With the global biodiversity crisis, DNA barcoding aims for fast species identification and cryptic species diversity revelation. For more than 10 years, large amounts of DNA barcode data have been accumulating in publicly available databases, most of which were conducted by distance or tree-building methods that have often been argued, especially for cryptic species revelation. In this context, overlooked cryptic diversity may exist in the available barcoding data. The character-based DNA barcoding, however, has a good chance for detecting the overlooked cryptic diversity. In this study, marine mollusk was as the ideal case for detecting the overlooked potential cryptic species from existing cytochrome c oxidase I (COI) sequences with character-based DNA barcode. A total of 1081 COI sequences of mollusks, belonging to 176 species of 25 families of Gastropoda, Cephalopoda, and Lamellibranchia, were conducted by character analysis. As a whole, the character-based barcoding results were consistent with previous distance and tree-building analysis for species discrimination. More importantly, quite a number of species analyzed were divided into distinct clades with unique diagnostical characters. Based on the concept of cryptic species revelation of character-based barcoding, these species divided into separate taxonomic groups might be potential cryptic species. The detection of the overlooked potential cryptic diversity proves that the character-based barcoding mode possesses more advantages of revealing cryptic biodiversity. With the development of DNA barcoding, making the best use of barcoding data is worthy of our attention for species conservation. PMID- 26899169 TI - Al atom on MoO3(010) surface: adsorption and penetration using density functional theory. AB - Interfacial issues, such as the interfacial structure and the interdiffusion of atoms at the interface, are fundamental to the understanding of the ignition and reaction mechanisms of nanothermites. This study employs first-principle density functional theory to model Al/MoO3 by placing an Al adatom onto a unit cell of a MoO3(010) slab, and to probe the initiation of interfacial interactions of Al/MoO3 nanothermite by tracking the adsorption and subsurface-penetration of the Al adatom. The calculations show that the Al adatom can spontaneously go through the topmost atomic plane (TAP) of MoO3(010) and reach the 4-fold hollow adsorption-site located below the TAP, with this subsurface adsorption configuration being the most preferred one among all plausible adsorption configurations. Two other plausible configurations place the Al adatom at two bridge sites located above the TAP of MoO3(010) but the Al adatom can easily penetrate below this TAP to a relatively more stable adsorption configuration, with a small energy barrier of merely 0.2 eV. The evidence of subsurface penetration of Al implies that Al/MoO3 likely has an interface with intermixing of Al, Mo and O atoms. These results provide new insights on the interfacial interactions of Al/MoO3 and the ignition/combustion mechanisms of Al/MoO3 nanothermites. PMID- 26899170 TI - DeconstructSigs: delineating mutational processes in single tumors distinguishes DNA repair deficiencies and patterns of carcinoma evolution. AB - BACKGROUND: Analysis of somatic mutations provides insight into the mutational processes that have shaped the cancer genome, but such analysis currently requires large cohorts. We develop deconstructSigs, which allows the identification of mutational signatures within a single tumor sample. RESULTS: Application of deconstructSigs identifies samples with DNA repair deficiencies and reveals distinct and dynamic mutational processes molding the cancer genome in esophageal adenocarcinoma compared to squamous cell carcinomas. CONCLUSIONS: deconstructSigs confers the ability to define mutational processes driven by environmental exposures, DNA repair abnormalities, and mutagenic processes in individual tumors with implications for precision cancer medicine. PMID- 26899171 TI - Reply to Topalovic and Janssens: Re: Quantifying the shape of the maximal expiratory flow-volume curve to address flow limitation. PMID- 26899172 TI - Understanding how the aggregation structure of starch affects its gastrointestinal digestion rate and extent. AB - Regulating the starch gastrointestinal digestion rate by control of its aggregation structure is an effective way, but the mechanism is still not clear. Multi-scale structure of waxy and normal wheat starches were studied by confocal laser scanning and scanning electron microscopes, as well as wide-angle and small angle X-ray techniques in this study. In vitro digestion kinetics of those two starches and structure-digestion relationship were also discussed. Both waxy and normal starches show A-type diffraction pattern, but waxy variety shows a slightly higher crystallinity. Small-angle X-ray scattering results show that waxy wheat starch has higher scattering peak intensity (Imax) and a larger crystallinity lamellar repeat distance (Lp) compared with the normal wheat starch. We suggested that the higher digestion rate of waxy starch at initial stage is mainly due to more small-size particles, but the higher crystallinity and the larger crystalline lamellar size limit the digestion extent. PMID- 26899173 TI - Ion activated in situ gel of gellan gum containing salbutamol sulphate for nasal administration. AB - Nasal delivery is the promising approach for rapid onset of action and avoids the first pass metabolism. The main aim of present study was to develop a novel mucoadhesive in situ gel of salbutamol sulphate using gellan gum and hydroxylpropyl methyl cellulose (HPMC) for nasal administration. The formulations were prepared so as to have gelation at physiological ion content after nasal administration. Developed formulations were evaluated for gelation, viscosity, drug content, in vitro mucoadhesion, in vitro drug release study, ex vivo permeation, and histopathology. Formulations showed pH in the range of nasal cavity and optimum viscosity for nasal administration. The mucoadhesive force depends upon concentration of HPMC and drug release was found to be 97.34% in 11h. The histopathology did not detect any damage during ex vivo permeation studies. Hence, in situ gel system of gellan gum may be a promising approach for nasal delivery of salbutamol sulphate for therapeutic improvement. PMID- 26899174 TI - Prospects of chitosan-based scaffolds for growth factor release in tissue engineering. AB - Tissue engineering is concerned about the rejuvenation and restoration of diseased and damages tissues/organs using man-made scaffolds that mimic the native environment of the cells. In recent years, a variety of biocompatible and biodegradable natural materials is employed for the fabrication of such scaffolds. Of these natural materials, chitosan is the most preferred one as it imitates the extracellular matrix (ECM) of the cells. Moreover, chitosan-based materials are pro-angiogenic and have antibacterial activity. These materials can be easily fabricated into the desired shape of the scaffolds that are suitable for tissue support and regeneration. Growth factors are small proteins/peptides that support and enhance the growth and differentiation of cells into a specific lineage. It has been observed that scaffolds capable of delivering growth factor promote tissue repair and regeneration at a faster rate when compared to scaffolds without growth factor. The present review focuses on the recent developments on chitosan-based scaffolds for the delivery of growth factors thereby improving and enhancing tissue regeneration. PMID- 26899175 TI - Effects of In utero environment and maternal behavior on neuroendocrine and behavioral alterations in a mouse model of prenatal trauma. AB - Maternal posttraumatic stress disorder (PTSD) following trauma exposure during pregnancy is associated with an increased risk of affective disorders in children. To investigate the mechanisms by which prenatal trauma and/or maternal PTSD affect brain development and behavior we established a mouse model of prenatal traumatic (PT) experience based on the application of an electric foot shock to C57Bl/6N female mice on the gestational day 12 during their pregnancy. The model is based on a previously validated animal model of PTSD. We found high anxiety levels and poor maternal care along with reduced serum prolactin and increased corticosterone levels in dams following maternal trauma (MT). PT-pups were born smaller and stayed smaller throughout their life. We show increased time and frequency of ultrasonic calls in PT-pups when separated from the mothers on the postnatal day (PND) 9. Cross-fostering experiments reveal lower anxiety levels in PT pups raised by healthy mothers as compared to trauma-naive pups raised by MT-dams. Importantly, the combination of prenatal trauma and being raised by a traumatized mother leads to: (1) the highest corticosterone levels in pups, (2) longest USV-call time and (3) highest anxiety levels in comparison to other experimental groups. Our data indicates a distinct change in maternal care following MT which is possibly associated with trauma-induced decrease in prolactin levels. Furthermore, we show that maternal behavior is crucial for the development of the offspring anxiety and specific aspects in maternal care overwrite to a significant extend the effects of in utero and postnatal environment. (c) 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1254-1265, 2016. PMID- 26899178 TI - Preschoolers have better long-term memory for rhyming text than adults. AB - The dominant view of children's memory is that it is slow to develop and is inferior to adults'. Here we pitted 4-year-old children against adults in a test of verbatim recall of verbal material. Parents read a novel rhyming verse (and an integrated word list) as their child's bedtime story on ten consecutive days. A group of young adults listened to the verse, matching the exposure of children. All participants subsequently performed a free-recall of the verse, verbatim. (Parents and young adults knew they would be tested; children did not.) Four-year olds significantly outperformed both their parents and the young adults. There were no significant differences in the ability to recall the gist of the verse, nor the integrated word list, allaying concerns about differences in engagement or motivation. Verbatim recall of verse is a skill amenable to practice, and children, we argue, by virtue of the prominence of verse in their culture and their reliance on oral transmission, have honed this skill to exceed adults'. PMID- 26899177 TI - EGCG in Green Tea Induces Aggregation of HMGB1 Protein through Large Conformational Changes with Polarized Charge Redistribution. AB - As a major effective component in green tea, (-)-epigallocatechin-3-gallate (EGCG)'s potential benefits to human health have been widely investigated. Recent experimental evidences indicate that EGCG can induce the aggregation of HMGB1 protein, a late mediator of inflammation, which subsequently stimulates the autophagic degradation and thus provides protection from lethal endotoxemia and sepsis. In this study, we use molecular dynamics (MD) simulations to explore the underlying molecular mechanism of this aggregation of HMGB1 facilitated by EGCG. Our simulation results reveal that EGCG firmly binds to HMGB1 near Cys106, which supports previous preliminary experimental evidence. A large HMGB1 conformational change is observed, where Box A and Box B, two homogenous domains of HMGB1, are repositioned and packed together by EGCG. This new HMGB1 conformation has large molecular polarity and distinctive electrostatic potential surface. We suggest that the highly polarized charge distribution leads to the aggregation of HMGB1, which differs from the previous hypothesis that two HMGB1 monomers are linked by the dimer of EGCG. Possible aggregating modes have also been investigated with potential of mean force (PMF) calculations. Finally, we conclude that the conformation induced by EGCG is more aggregation-prone with higher binding free energies as compared to those without EGCG. PMID- 26899176 TI - Establishment of human iPSC-based models for the study and targeting of glioma initiating cells. AB - Glioma tumour-initiating cells (GTICs) can originate upon the transformation of neural progenitor cells (NPCs). Studies on GTICs have focused on primary tumours from which GTICs could be isolated and the use of human embryonic material. Recently, the somatic genomic landscape of human gliomas has been reported. RTK (receptor tyrosine kinase) and p53 signalling were found dysregulated in ~90% and 86% of all primary tumours analysed, respectively. Here we report on the use of human-induced pluripotent stem cells (hiPSCs) for modelling gliomagenesis. Dysregulation of RTK and p53 signalling in hiPSC-derived NPCs (iNPCs) recapitulates GTIC properties in vitro. In vivo transplantation of transformed iNPCs leads to highly aggressive tumours containing undifferentiated stem cells and their differentiated derivatives. Metabolic modulation compromises GTIC viability. Last, screening of 101 anti-cancer compounds identifies three molecules specifically targeting transformed iNPCs and primary GTICs. Together, our results highlight the potential of hiPSCs for studying human tumourigenesis. PMID- 26899180 TI - Serum nitrate and nitrite are associated with the prevalence of various chronic diseases except cancer. AB - BACKGROUND: Nitric oxide and its metabolites, nitrate and nitrite, are important regulators linked to various diseases. We studied the association of fasting serum concentrations of nitrate and nitrite, combined as NOx, without special diet, with the prevalence of various chronic diseases. METHODS: Fasting concentrations of NOx were assayed in a cohort of 1087 patients recruited to Stress Aging and Health in Russia study that represents male and female population in Moscow, Russia, over 55 years of age. Chronic diseases were recorded based on anamnesis and additional assays were run to characterize immune status and lipid and carbohydrate metabolism. Odds ratios were calculated to associate NOx concentrations with prevalence of chronic diseases in pooled deciles below or above borderline. RESULTS: NOx over 44.7 uM were associated with increased prevalence of various chronic diseases such as diabetes type II, hyperthyroidism, coronary heart disease, gout and thrombosis/stroke. NOx 65.3 uM and above were associated with lowered prevalence of osteoporosis. NOx levels of 74.6 uM and above were associated with significantly higher number of patients who abstain from consumption of alcoholic beverages. NOx were not associated with cancer. CONCLUSIONS: Thus, fasting concentrations of NOx in serum can be an important diagnostic parameter characteristic for specific chronic diseases. PMID- 26899179 TI - Transcripts of genes encoding reproductive neuroendocrine hormones and androgen receptor in the brain and testis of goldfish exposed to vinclozolin, flutamide, testosterone, and their combinations. AB - Vinclozolin (VZ) is a pesticide that acts as an anti-androgen to impair reproduction in mammals. However, VZ-induced disruption of reproduction is largely unknown in fish. In the present study, we have established a combination exposure in which adult goldfish were exposed to VZ (30 and 100 MUg/L), anti androgen flutamide (Flu, 300 MUg/L), and androgen testosterone (T, 1 MUg/L) to better understand effects of VZ on reproductive endocrine system. mRNA levels of kisspeptin (kiss-1 and kiss-2) and its receptor (gpr54), salmon gonadotropin releasing hormone (gnrh3) and androgen receptor (ar) in the mid-brain, and luteinizing hormone receptor (lhr) in the testis were analyzed and compared with those of control following 10 days of exposure. kiss-1 mRNA level was increased in goldfish exposed to 100 ug/L VZ and to Flu, while kiss-2 mRNA level was increased following exposure to Flu and to combinations of 30 ug/L VZ with Flu, 100 ug/L VZ with T, and Flu with T. gpr54 mRNA level was increased in goldfish exposed to Flu and to combination of 30 ug/L VZ with Flu and 100 ug/L VZ with T. gnrh3 mRNA level was increased in goldfish exposed to 100 ug/L VZ, to Flu, and to combinations of 30 ug/L VZ with Flu, 100 ug/L VZ with T, and Flu with T. The mid brain ar mRNA level was increased in goldfish exposed to Flu and to combinations of 30 ug/L VZ with Flu, 100 ug/L VZ with T, and Flu with T. Testicular lhr mRNA level was increased in goldfish exposed to Flu and to combination of 30 ug/L VZ with Flu. These results suggest that VZ and Flu are capable of interfering with kisspeptin and GnRH systems to alter pituitary and testicular horonal functions in adult goldfish and the brain ar mediates VZ-induced disruption of androgen production. PMID- 26899181 TI - Sensory perturbations using suture and sutureless repair of transected median nerve in rats. AB - The effects of changes to cold, mechanical, and heat thresholds following median nerve transection with repair by sutures (Su) or Rose Bengal adhesion (RA) were compared to sham-operated animals. Both nerve-injured groups showed a transient, ipsilateral hyposensitivity to mechanical and heat stimuli followed by a robust and long-lasting hypersensitivity (6-7 weeks) with gradual recovery towards pre injury levels by 90 days post-repair. Both tactile and thermal hypersensitivity were seen in the contralateral limb that was similar in onset but differed in magnitude and resolved more rapidly compared to the injured limb. Prior to injury, no animals showed any signs of aversion to cold plate temperatures of 4 16 degrees C. After injury, animals showed cold allodynia, lasting for 7 weeks in RA-repaired rats before recovering towards pre-injury levels, but were still present at 12 weeks in Su-repaired rats. Additionally, sensory recovery in the RA group was faster compared to the Su group in all behavioural tests. Surprisingly, sham-operated rats showed similar bilateral behavioural changes to all sensory stimuli that were comparable in onset and magnitude to the nerve-injured groups but resolved more quickly compared to nerve-injured rats. These results suggest that nerve repair using a sutureless approach produces an accelerated recovery with reduced sensorimotor disturbances compared to direct suturing. They also describe, for the first time, that unilateral forelimb nerve injury produces mirror-image-like sensory perturbations in the contralateral limb, suggesting that the contralateral side is not a true control for sensory testing. The potential mechanisms involved in this altered behaviour are discussed. PMID- 26899182 TI - A selected reaction monitoring-based analysis of acute phase proteins in interstitial fluids from experimental equine wounds healing by secondary intention. AB - In horses, pathological healing with formation of exuberant granulation tissue (EGT) is a particular problem in limb wounds, whereas body wounds tend to heal without complications. Chronic inflammation has been proposed to be central to the pathogenesis of EGT. This study aimed to investigate levels of inflammatory acute phase proteins (APPs) in interstitial fluid from wounds in horses. A novel approach for absolute quantification of proteins, selected reaction monitoring (SRM)-based mass spectrometry in combination with a quantification concatamer (QconCAT), was used for the quantification of five established equine APPs (fibrinogen, serum amyloid A, ceruloplasmin, haptoglobin, and plasminogen) and three proposed equine APPs (prothrombin, alpha-2-macroglobulin, and alpha-1 antitrypsin). Wound interstitial fluid was recovered by large pore microdialysis from experimental body and limb wounds from five horses at days 1, 2, 7, and 14 after wounding and healing without (body) and with (limb) the formation of EGT. The QconCAT included proteotypic peptides representing each of the protein targets and was used to direct the design of a gene, which was expressed in Escherichia coli in a media supplemented with stable isotopes for metabolically labeling of standard peptides. Co-analysis of wound interstitial fluid samples with the stable isotope-labeled QconCAT tryptic peptides in known amounts enabled quantification of the APPs in absolute terms. The concentrations of fibrinogen, haptoglobin, ceruloplasmin, prothrombin, and alpha-1-antitrypsin in dialysate from limb wounds were significantly higher than in dialysate from body wounds. This is the first report of simultaneous analysis of a panel of APPs using the QconCAT-SRM technology. The microdialysis technique in combination with the QconCAT-SRM-based approach proved useful for quantification of the investigated proteins in the wound interstitial fluid, and the results indicated that there is a state of sustained inflammation in equine wounds healing with formation of EGT. PMID- 26899183 TI - Predelivery maternal fibrinogen as a predictor of blood loss after vaginal delivery. AB - PURPOSE: The present study investigated whether fibrinogen level during the first stage of labor is associated with bleeding severity in the third stage of labor. METHODS: We prospectively enrolled 1019 pregnant women with planned vaginal delivery. Upon admission to delivery, maternal fibrinogen levels, hemoglobin content, and coagulation parameters were evaluated. Blood loss in the third stage of labor was systematically measured using a calibrated collecting drape. Univariate and multivariate analyses were performed to identify predictors of PPH (blood loss >=500 mL) and S-PPH (blood loss >=1000 mL). RESULTS: Among 809 vaginal deliveries, mean maternal predelivery fibrinogen was 4.65 +/- 0.77 g/L, PPH incidence was 12 %, S-PPH incidence was 3.5 %, and median blood loss was 250 mL. Fibrinogen levels were significantly lower in women with S-PPH (4.22 +/- 0.82 g/L) than without S-PPH (4.67 +/- 0.75 g/L; p = 0.004), but did not significantly differ between women with PPH (4.67 +/- 0.84 g/L) and those without PPH (4.67 +/- 0.75 g/L; p = 0.985). Instrumental delivery and predelivery fibrinogen levels were independent predictors of S-PPH. Primiparous status, birth weight >4000 g, genital tract laceration, episiotomy and instrumental delivery were independent predictors of PPH. CONCLUSION: For each 1 g/L increase of predelivery fibrinogen level, the risk of S-PPH after vaginal delivery decreases by a factor of 0.405 (95 % CI 0.219-0.750; p = 0.004). PMID- 26899184 TI - Radiolabeled Nanoparticles for Cancer Diagnosis and Therapy. AB - Cancer remains as one of the major causes of death worldwide. The emergence of nanotechnology has opened new avenues for the development of nanoparticle (NP)- based diagnostic and therapeutic tools. NPs of different chemical composition, size, shape and surface decoration can be prepared using a wide variety of synthetic strategies. Subsequent radiolabelling with positron or gamma emitters results in potential diagnostic agents which may offer improved selectivity and/or specificity for the target organ or tissue, enabling the acquisition of images with higher signal-to-contrast ratio. Incorporation of alpha or beta emitters leads to therapeutic agents with application in the field of radiotherapy. Here, we first describe the different labeling strategies reported so far for the incorporation of radionuclides into NPs. Recent advances in the use of nanoparticulate constructs both in the diagnostic and therapeutic arenas are then discussed and examples of their application are briefly discussed. PMID- 26899185 TI - Effects of Anticancer Drugs in Reproductive Parameters of Juvenile Male Animals and Role of Protective Agents. AB - Nowadays, the advances in knowledge about oncologic treatment have led to an increase in survival rate for cancer patients and, consequently, a growing concern about the adverse effects of treatment in medium and long term, in order to ensure the future quality of life. For male patients in reproductive age or younger, one of the key concerns after cancer therapy is their ability to father children, since anticancer drugs exert cytotoxic effects on germ cells. Considering the incidence of cancer in children and adolescents and the vulnerability of these developmental phases to chemical injuries, this review is an attempt to highlight the importance of juvenile experimental models to test new anticancer drugs and agents with protective action. There is a relative scarcity of studies investigating the effects of chemotherapy in juvenile animals and an urgent need for further information. As far as this review was able to recover, available data about reproductive toxicology related to peripubertal treatment with anticancer drugs includes only the following pharmaceuticals: toposide, doxorrubicin, cisplatin, ciclophosphamide, cytarabine, flutamide and procarbazine. Together with the evaluation of adverse effects of anticancer drugs, is necessary to investigate possible protective agents to be pre-, co-, or post administrated with chemotherapy. Modern technologies and increasing knowledge about the cancer biology have allowed studies of new chemotherapy strategies, more effective and selective. Many of these compounds are derived from toxins and metabolites of microorganisms, plants, and animals, being a number of them isolated from marine sources, a relatively unexplored environment. Investment in research programs in bioprospecting, especially in marine environments, and pharmaceutical field, including toxicology risk evaluation, are crucial to discovery and improve new anticancer treatments. PMID- 26899186 TI - Recent Advances in Heterocyclic Tubulin Inhibitors Targeting the Colchicine Binding Site. AB - Microtubules are involved in many critical cellular processes including cell division, cell shape maintenance, vesicle transportation and motility regulation. Disruption of tubulin dynamics is a well-validated cancer drug target with several FDA approved, highly efficacious tubulin inhibitors targeting the taxane or the vinca binding sites. Despite the tremendous successes for these clinical tubulin inhibitors, their limitations are also apparent, particularly in the development of transporter mediated drug resistance. While currently there are no FDA approved inhibitors targeting the colchicine binding site in tubulin, extensive preclinical studies have suggested that colchicine binding site inhibitors (CBSIs) have significantly less susceptibility to transporter medicated drug resistance. The presence of one or more heterocyclic moieties is often critical for the antiproliferative activities for most of these CBSIs. This article aims to review the structures and antiproliferative activities of most recently developed heterocyclic CBSIs from 2013 to present. We focus this review on compounds that are designed based on the CA-4, chalcone and PTOX scaffolds which are well established to interact with the colchicine binding site in tubulin. PMID- 26899188 TI - Macromolecular Drug Targets in Cancer Treatment and Thiosemicarbazides as Anticancer Agents. AB - Cancer is known as abnormal cell division and consisting of a group of diseases on various organ tissues. Many therapies are available in cancer treatment such as chemotherapy, radiotherapy etc. Without damaging normal tissue, there is a huge need for specified anticancer drugs which have effect only on abnormal cancer cells. Therefore, advances in anticancer drug discovery in treating cancer in the recent years, directed towards to the macromolecular targets. Heterocyclic molecules, such as fluconazole, acetazolamide, etc., have a significant role in health care and pharmaceutical drug design. Thiosemicarbazides (NH2-NH CSNH2) are the simplest hydrazine derivatives of thiocarbamic acid and are not only transition compounds, but they are also very effective organic compounds. Thiosemicarbazides possess an amide and amine protons, carbonyl and thione carbons. These structures have attracted the attention of the researchers in the development of novel compounds with anticonvulsant, antiviral, anti inflammatory, antibacterial, antimycobacterial, antifungal, antioxidant and anticancer activities. Recently, a number of thiosemicarbazides are available commercially as anticancer drugs for novel anticancer drug discovery. Antineoplastic or anticancer drugs prevent or inhibit the maturation and proliferation of neoplasms. These observations have been guiding the researchers for the development of new thiosemicarbazides that possess anticancer activity. PMID- 26899187 TI - Targeting the Folate Receptor: Effects of Conjugating Folic Acid to DOX Loaded Polymeric Micelles. AB - In this paper, we report on a potential cancer drug delivery system that utilizes the ligand targeting of the folate receptor. Our drug delivery system consists of Pluronic-P105 micelles, targeted with folic acid moieties. A melanoma folate positive (FR+) (B16-F10), and a fibroblast folate negative (FR-) (NIH-3T3) cell lines are used to compare the cellular accumulation of a chemotherapeutic drug (Doxorubicin) when the delivery is mediated by folated Pluronic P105 micelles. In order to obtain a proper comparison, we corrected for the quenching of Doxorubicin by folic acid molecules and illustrated the significant effect of quenching on the analysis of similar systems. Results show an 80% increase in the accumulation of the antineoplastic agent in the FR+ cell line, when compared to the FR- cell line, thus providing evidence that the efficacy of Pluronic micelles, as drug delivery vehicles, can be enhanced via folic acid targeting. PMID- 26899189 TI - Controlling the Two-Photon-Induced Photon Cascade Emission in a Gd(3+)/Tb(3+) Codoped Glass for Multicolor Display. AB - We reported the first observation of the two-photon-induced quantum cutting phenomenon in a Gd(3+)/Tb(3+)-codoped glass in which two photons at ~400 nm are simultaneously absorbed, leading to the cascade emission of three photons in the visible spectral region. The two-photon absorption induced by femtosecond laser pulses allows the excitation of the energy states in Gd(3+) which are inactive for single-photon excitation and enables the observation of many new electric transitions which are invisible in the single-photon-induced luminescence. The competition between the two-photon-induced photon cascade emission and the single photon-induced emission was manipulated to control the luminescence color of the glass. We demonstrated the change of the luminescence color from red to yellow and eventually to green by varying either the excitation wavelength or the excitation power density. PMID- 26899190 TI - HLA-A*11:231, a novel variant of HLA-A*11, found in a Taiwanese hematopoietic stem cell donor. AB - One nucleotide substitution at residue 517 of HLA-A*11:01:01:01 results in a novel allele, HLA-A*11:231. PMID- 26899191 TI - Epigenetic Treatment of Neuropsychiatric Disorders: Autism and Schizophrenia. AB - Neuropsychiatric disorders are a heterogeneous group of conditions that often share underlying mitochondrial dysfunction and biological pathways implicated in their pathogenesis, progression, and treatment. To date, these disorders have proven notoriously resistant to molecular-targeted therapies, and clinical options are relegated to interventional types, which do not address the core symptoms of the disease. In this review, we discuss emerging epigenetic-driven approaches using novel acylcarnitine esters (carnitinoids) that act on master regulators of antioxidant and cytoprotective genes and mitophagic pathways. These carnitinoids are actively transported, mitochondria-localizing, biomimetic coenzyme A surrogates of short-chain fatty acids, which inhibit histone deacetylase and may reinvigorate synaptic plasticity and protect against neuronal damage. We outline these neuroprotective effects in the context of treatment of neuropsychiatric disorders such as autism spectrum disorder and schizophrenia. PMID- 26899193 TI - Missing Lunch is Associated with Lower Intakes of Micronutrients from Foods and Beverages among Children and Adolescents in the United States. AB - BACKGROUND: In the United States, the lunch meal contributes more than 20% of the daily intakes of most micronutrients for children and adolescents consuming lunch. Seven percent to 20% of children and adolescents in the United States do not eat lunch on a given day. OBJECTIVE: To identify differences in total micro- and macronutrient intakes of children consuming and missing lunch on a given day. DESIGN: Cross-sectional secondary analysis of the combined National Health and Nutrition Examination Surveys 2009-2010 and 2011-2012. Dietary intake was assessed using the first day 24-hour recall of each respondent. PARTICIPANTS AND SETTINGS: The National Health and Nutrition Examination Survey sample represents the total noninstitutionalized civilian population residing in the United States. The sample used in this study included 4,755 children aged 4 to 18 years with complete data for all analyses. MAIN OUTCOME MEASURES: Total day, lunch, and nonlunch micronutrients, macronutrients, solid fats, and added sugar intakes were examined. STATISTICAL ANALYSES PERFORMED: Linear regression models controlling for age, sex, race/ethnicity, household poverty status, and weekend were used to compare dietary intakes of lunch consumers and nonconsumers. Intakes from nonlunch sources were examined to determine the extent to which differences between lunch consumers and nonconsumers could be attributed to the lunch meal. RESULTS: Missing lunch was associated with lower micronutrient intakes, with the lunch meal primarily responsible for the higher micronutrient intakes of lunch consumers compared with nonconsumers. Missing lunch was also associated with lower energy, fiber, and sodium intakes. Added sugar and solid fat intakes of lunch consumers and nonconsumers were not significantly different. CONCLUSIONS: This study identifies potential concerns for children missing lunch with respect to micronutrient intakes and shows that the lunches consumed by children in the United States are an important source of essential nutrients, but also less healthful dietary components. PMID- 26899192 TI - Antioxidant activities and liquid chromatography with electrospray ionization tandem mass spectrometry characterization and quantification of the polyphenolic contents of Rumex nervosus Vahl leaves and stems. AB - In the present study, four compounds, viz. chlorogenic acid, catechin, orientin, and apigenin-O-acetylglycoside among 18 polyphenol compounds (17 flavonoids and one hydroxycinnamic acid derivative) were characterized for the first time in Rumex nervosus leaves and stems by using liquid chromatography with electrospray ionization tandem mass spectrometry. Method validation in terms of determination coefficient, limits of detection, and quantification were >= 0.9979, 0.68-1.61, and 2.27-5.38 mg/L, respectively. Accuracy, expressed as percent recovery for two spiking levels (10 and 50 mg/L), were in the range 78.9-110.6% with the exception of caffeic acid. The relative standard deviations were 1-17%. The total polyphenol content was higher by approximately two times in the leaf (1073 mg/kg fresh sample) than in the stem (519.86 mg/kg fresh sample). The antioxidant effects increased in a dose-dependent manner, and the scavenging activities, investigated by measuring 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) scavenging activity, ferrous ions chelating activity, superoxide anion radical scavenging activity, and ferric reducing antioxidant power activity, were significant (p < 0.05) using low concentrations of the leaf extract. Overall, the present study suggests that different parts of R. nervosus have great potential for producing a range of extracts with potential applications in medicine. PMID- 26899194 TI - A Readily Available, Inexpensive, and Reusable Simulation Model for Teaching Ultrasound-Guided Abscess Identification and Drainage. AB - BACKGROUND: The use of point-of-care ultrasonography as a noninvasive diagnostic tool for soft tissue infections has been shown to be superior to clinical judgment alone in determining the presence or absence of an occult abscess. As ultrasound-guided procedures become standard of care, there is an increasing demand to develop better and inexpensive simulation models to educate trainees. To date, there are no low-cost models for abscess simulation that can be constructed with minimal preparation time, be reused, and withstand multiple procedural attempts. OBJECTIVE: To create an inexpensive, readily available, and reusable homemade ultrasound phantom that simulates a superficial soft tissue abscess and can be easily constructed. DISCUSSION: We experimented with precooked polenta to create a model that would appear similar to human soft tissue under ultrasound examination. Paintballs were embedded in the polenta and evaluated at different depths until a sonographically satisfactory phantom abscess model was obtained. The use of a precooked commercial polenta phantom and commercial paintballs required minimal preparation and closely replicated a superficial soft tissue abscess on ultrasonographic examination. Various paintball brands and sizes were evaluated to confirm ease of reproducibility. The polenta can be reshaped easily and the model may be punctured or incised multiple times. CONCLUSION: A homemade high-fidelity simulation phantom that simulates an abscess in superficial soft tissue can be made inexpensively in <5 min and reused for numerous trainees. This model allows for training for procedures such as ultrasound-guided abscess drainage. PMID- 26899195 TI - Asymptomatic Sustained Polymorphic Ventricular Tachycardia in a Patient with a Left Ventricular Assist Device: Case Report and what the Emergency Physician Should Know. AB - BACKGROUND: Left ventricular assist devices (LVADs) are a viable treatment option for patients with end-stage heart failure. LVADs can improve survival, quality of life, and functional status. The indications for LVAD placement to support left ventricular function are temporary support, a bridge to transplantation, or destination therapy. CASE REPORT: A 61-year-old man with past medical history significant for advanced congestive heart failure from ischemic cardiomyopathy, status post LVAD (HeartMate II; Thoratec Corporation, Pleasanton, CA) placement 2009 as destination therapy, presented to the Emergency Department (ED) with implantable cardiac defibrillators firing four times that morning. While in the care of Emergency Medical Services, he was in ventricular tachycardia, and they gave him a bolus of amiodarone 150 mg intravenously prior to arrival in the ED. He was reportedly alert and oriented without any chest pain on arrival to the ED, where an electrocardiogram was obtained showing polymorphic ventricular tachycardia. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physicians must be familiar with the atypical presentations of potentially lethal dysrhythmias in this patient population. They must also be familiar with the major adverse events after LVAD implantation. These include device malfunction, cardiac dysrhythmias, bleeding, thromboembolism, neurological events, and infection. The causes of device malfunction can include thrombus formation with hemolysis, mechanical failure of the impeller, and driveline lead fractures with electric failure. Although time is critical in the heart failure patient with an LVAD failure or complication, expert consultation with cardiology or the LVAD specialist should occur when possible. PMID- 26899196 TI - Macrophage miRNAs in atherosclerosis. AB - The discovery of endogenous microRNAs (miRNAs) in the early 1990s has been followed by the identification of hundreds of miRNAs and their roles in regulating various biological processes, including proliferation, apoptosis, lipid metabolism, glucose homeostasis and viral infection Esteller (2011), Ameres and Zamore (2013) [1,2]. miRNAs are small (~22 nucleotides) non-coding RNAs that function as "rheostats" to simultaneously tweak the expression of multiple genes within a genetic network, resulting in dramatic functional modulation of biological processes. Although the last decade has brought the identification of miRNAs, their targets and function(s) in health and disease, there remains much to be deciphered from the human genome and its complexities in mechanistic regulation of entire genetic networks. These discoveries have opened the door to new and exciting avenues for therapeutic interventions to treat various pathological diseases, including cardiometabolic diseases such as atherosclerosis, diabetes and obesity. In a complex multi-factorial disease like atherosclerosis, many miRNAs have been shown to contribute to disease progression and may offer novel targets for future therapy. This article is part of a Special Issue entitled: MicroRNAs and lipid/energy metabolism and related diseases edited by Carlos Fernandez-Hernando and Yajaira Suarez. PMID- 26899197 TI - Lipotoxicity in obesity and diabetes-related cardiac dysfunction. AB - Patients with type 2 diabetes (T2D) are at increased risk for cardiovascular diseases including diabetic cardiomyopathy, which is ventricular dysfunction independent of underlying coronary artery disease and/or hypertension. With numerous advancements in our ability to detect ventricular dysfunction, as well as the molecular mechanisms contributing to ventricular dysfunction in diabetic patients, it is now appreciated that diabetic cardiomyopathy is becoming more prevalent in our population. In spite of these advancements, we do not have any specific therapies currently approved for treating this condition. As obesity increases the risk for both T2D and cardiovascular disease, it has been postulated that obesity-mediated alterations in myocardial lipid metabolism are critical to the pathophysiology of diabetic cardiomyopathy. Indeed, animal studies have provided strong evidence that alterations in either myocardial fatty acid uptake or fatty acid beta-oxidation lead to the accumulation of various lipid intermediates including triacylglycerol, diacylglycerol, ceramide, long chain acyl CoA, acylcarnitine, and many others that are tightly linked to the progression of ventricular dysfunction. We review herein why lipid intermediates accumulate in the heart during obesity and/or T2D, with a focus on which of these various lipid intermediates may be responsible for cardiac lipotoxicity, and whether findings in animal models are relevant to humans. An improved understanding of how these lipid intermediates accumulate in the heart and how they produce cardiac toxicity may lead to the discovery of novel targets to pursue for the treatment of human diabetic cardiomyopathy. This article is part of a Special Issue entitled: Heart Lipid Metabolism edited by G.D. Lopaschuk. PMID- 26899198 TI - Telangiectasia macularis eruptiva perstans (TMEP): A form of cutaneous mastocytosis with potential systemic involvement. AB - BACKGROUND: Telangiectasia macularis eruptiva perstans (TMEP) has not been fully characterized. OBJECTIVE: We sought to estimate the frequency and clinical characteristics of TMEP in a cohort of adult patients with cutaneous mastocytosis, and to assess the presence of systemic involvement. METHODS: We included all consecutive patients evaluated for cutaneous mastocytosis in 2 centers: the Mastocytosis Competence Center of the Midi-Pyrenees from May 2006 to December 2013, and the French Reference Center for Mastocytosis from January 2008 to September 2013. Skin phenotype, histopathology, presence of KIT mutation in the skin, and assessment of systemic involvement according to World Health Organization (WHO) criteria were prospectively investigated. RESULTS: Of 243 patients with cutaneous mastocytosis, 34 (14%) were given a diagnosis of TMEP. The diagnosis of systemic mastocytosis was established in 16 patients (47%) with TMEP. Three patients (9%) had aggressive systemic mastocytosis (C-findings according to WHO). In all, 32 patients (94%) exhibited at least 1 mast cell activation-related symptom. LIMITATIONS: Patient recruitment was undertaken at 2 referral centers with expertise in the diagnosis and treatment of mastocytosis so that the clinical findings and incidence of systemic involvement may be overestimated in comparison with the overall population of patients with TMEP. CONCLUSION: TMEP accounts for about 14% of patients with cutaneous mastocytosis. The disease manifests as mast cell activation symptoms in almost all patients and can be associated with systemic involvement in about 50% of cases. PMID- 26899200 TI - Characteristics, treatment, and survival of invasive malignant melanoma (MM) in giant pigmented nevi (GPN) in adults: 976 cases from the National Cancer Data Base (NCDB). AB - BACKGROUND: Malignant melanoma (MM) arising in a giant pigmented nevus (GPN) is a rare disease in adults with no large series published to our knowledge. OBJECTIVE: We sought to describe the characteristics, treatment, and survival of MM in GPN for adults. METHODS: Adults with invasive MM in GPN (n = 976) reported to the National Cancer Data Base from 1998 to 2012 were evaluated for patient and tumor characteristics, treatment, and survival. For comparison, data from adults with invasive superficial spreading melanoma (SSM) (n = 111,870) and nodular melanoma (n = 35,962) were used. RESULTS: Compared with patients with SSM, patients with MM in GPN had a thicker Breslow depth, more positive lymph nodes, and distant metastasis more frequently. Multivariate analysis identified age older than 65 years, Breslow thickness greater than 2 mm, presence of ulceration, presence of distant metastasis, and positive margins as independent predictors of survival in patients with MM in GPN. At all stages, having MM in GPN has similar overall survival compared with SSM. LIMITATIONS: The study is retrospective and registry-based. CONCLUSIONS: Invasive MM in GPN occurs in adults, with overall survival similar to SSM. Clinicians should be aware of the continued risk of MM in adults with GPN with low threshold for biopsy. PMID- 26899199 TI - Tofacitinib, an oral Janus kinase inhibitor, for the treatment of chronic plaque psoriasis: Long-term efficacy and safety results from 2 randomized phase-III studies and 1 open-label long-term extension study. AB - BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor being investigated for psoriasis. OBJECTIVES: We sought to report longer-term tofacitinib efficacy and safety in patients with moderate to severe psoriasis. METHODS: Data from 2 identical phase-III studies, Oral-treatment Psoriasis Trial Pivotal 1 and 2, were pooled with data from these patients in an ongoing open-label long-term extension study. Patients (n = 1861) were randomized 2:2:1 to tofacitinib 5 mg, 10 mg, or placebo twice daily (BID). At week 16, placebo patients were rerandomized to tofacitinib. Pivotal study participants could enroll into the long-term extension where they received tofacitinib at 10 mg BID for 3 months, after which dosing could be 5 or 10 mg BID. RESULTS: At week 28, the proportions of patients randomized to tofacitinib 5 and 10 mg BID achieving 75% or greater reduction in Psoriasis Area and Severity Index score from baseline were 55.6% and 68.8%, and achieving Physician Global Assessment of clear or almost clear were 54.7% and 65.9%. Efficacy was maintained in most patients through 24 months. Serious adverse events and discontinuations because of adverse events were reported in less than 11% of patients over 33 months of tofacitinib exposure. LIMITATIONS: There was no dose comparison beyond week 52. CONCLUSIONS: Oral tofacitinib demonstrated sustained efficacy in patients with psoriasis through 2 years, with 10 mg BID providing greater efficacy than 5 mg BID. No unexpected safety findings were observed. PMID- 26899201 TI - Numerical study of Hough technique in surgery of otosclerosis, using the finite element method. AB - PURPOSE: Otosclerosis is a metabolic bone disease of the otic capsule that can cause the stapes fixation, resulting in conductive hearing loss or, in a profound sensorineural deafness threshold. Surgery is one of the possible treatments for the otosclerosis. To repair small focus of otosclerosis in the anterior crus of the stapes, in 1960, Hough suggested the implementation of a technique in which part of the anterior crus is fractured and the stapes turned. As a result, the posterior crus of the stapes is the only connection with the inner ear. In this work, the outcome of Hough's surgical technique was simulated. METHODS: Based on computerized images, a finite element model of middle ear ossicles and tympanic membrane was created, as well as a model where the stapes has changed. The discretization of the tridimensional solid model was made using the ABAQUS software. The mechanical properties used were taken from the literature and adequate boundary conditions were applied. RESULTS: The results obtained with the Hough technique simulation were compared with a representative model of the normal ear, taking into account the displacements obtained on the central part of the stapes footplate and the maximum principal stress in the stapes crus. CONCLUSIONS: The results obtained are closer to the normal ear model, therefore Hough technique stands out as a good option to correct small focus of otosclerosis. PMID- 26899204 TI - A new cadmium-doped titanium-oxo cluster with stable photocatalytic H2 evolution properties. AB - A new Cd-doped titanium-oxo cluster (TOC) stabilized by tert-butylacetic acid ligands has been prepared through an easily handled solvothermal reaction; photocatalytic studies indicate that it displays good H2 evolution ability (3.15 MUmol h(-1)), and moreover preserves high catalytic stability. PMID- 26899202 TI - VEGF stimulates intramembranous bone formation during craniofacial skeletal development. AB - Deficiency of vascular endothelial growth factor A (VEGF) has been associated with severe craniofacial anomalies in both humans and mice. Cranial neural crest cell (NCC)-derived VEGF regulates proliferation, vascularization and ossification of cartilage and membranous bone. However, the function of VEGF derived from specific subpopulations of NCCs in controlling unique aspects of craniofacial morphogenesis is not clear. In this study a conditional knockdown strategy was used to genetically delete Vegfa expression in Osterix (Osx) and collagen II (Col2)-expressing NCC descendants. No major defects in calvaria and mandibular morphogenesis were observed upon knockdown of VEGF in the Col2(+) cell population. In contrast, loss of VEGF in Osx(+) osteoblast progenitor cells led to reduced ossification of calvarial and mandibular bones without affecting the formation of cartilage templates in newborn mice. The early stages of ossification in the developing jaw revealed decreased initial mineralization levels and a reduced thickness of the collagen I (Col1)-positive bone template upon loss of VEGF in Osx(+) precursors. Increased numbers of proliferating cells were detected within the jaw mesenchyme of mutant embryos. Explant culture assays revealed that mandibular osteogenesis occurred independently of paracrine VEGF action and vascular development. Reduced VEGF expression in mandibles coincided with increased phospho-Smad1/5 (P-Smad1/5) levels and bone morphogenetic protein 2 (Bmp2) expression in the jaw mesenchyme. We conclude that VEGF derived from Osx(+) osteoblast progenitor cells is required for optimal ossification of developing mandibular bones and modulates mechanisms controlling BMP-dependent specification and expansion of the jaw mesenchyme. PMID- 26899205 TI - Multivariate calibration of the degree of crystallinity in intact pellets by X ray powder diffraction. AB - XRPD is the method of choice to determine crystalline content in an amorphous environment. While several studies describe its use on powders, little information is available on its performance on finished products. The method's use may be limited not only by the need of sample pretreatment and its validation but also by the propensity of some materials to recrystallize when exposed to heat or mechanical stress. In this work the authors describe an attempt at constructing a model based on the XRPD measurement of intact layered pellets using univariate methods based on peak heights and PLS regression. Results indicate that neither the goodness-of-fit (below 0.9 for all tested variables), nor the RMSEC values (above 5 for all tested variables) of any model based on peak height were good enough to consider them for everyday use. PLS regression however provided a model with improved characteristics (R(2)=0.9581, RMSEC=3.04) despite the low API content and individual loading characteristics also reflected the validity of the model. PLS analysis also indicated that a specific sample may be different in some formulation characteristic that did not register on other examinations. This further indicates the method's usefulness in the analysis of intact dosage forms. PMID- 26899203 TI - The ameloblastin extracellular matrix molecule enhances bone fracture resistance and promotes rapid bone fracture healing. AB - The extracellular matrix (ECM) provides structural support, cell migration anchorage, cell differentiation cues, and fine-tuned cell proliferation signals during all stages of bone fracture healing, including cartilaginous callus formation, callus remodeling, and bony bridging of the fracture gap. In the present study we have defined the role of the extracellular matrix protein ameloblastin (AMBN) in fracture resistance and fracture healing of mouse long bones. To this end, long bones from WT and AMBN(Delta5-6) truncation model mice were subjected to biomechanical analysis, fracture healing assays, and stem cell colony formation comparisons. The effect of exogenous AMBN addition to fracture sites was also determined. Our data indicate that lack of a functional AMBN in the bone matrix resulted in 31% decreased femur bone mass and 40% reduced energy to failure. On a cellular level, AMBN function inhibition diminished the proliferative capacity of fracture repair callus cells, as evidenced by a 58% reduction in PCNA and a 40% reduction in Cyclin D1 gene expression, as well as PCNA immunohistochemistry. In terms of fracture healing, AMBN truncation was associated with an enhanced and prolonged chondrogenic phase, resulting in delayed mineralized tissue gene expression and delayed ossification of the fracture repair callus. Underscoring a role of AMBN in fracture healing, there was a 6.9-fold increase in AMBN expression at the fracture site one week after fracture, and distinct AMBN immunolabeling in the fracture gap. Finally, application of exogenous AMBN protein to bone fracture sites accelerated callus formation and bone fracture healing (33% increase in bone volume and 19% increase in bone mineral density), validating the findings of our AMBN loss of function studies. Together, these data demonstrate the functional importance of the AMBN extracellular matrix protein in bone fracture prevention and rapid fracture healing. PMID- 26899206 TI - Designing Peptide Bunches on Nanocage for Bispecific or Superaffinity Targeting. AB - Ferritin cage nanoparticles are promising platforms for targeted delivery of imaging and therapeutic agents because their cage structure can accommodate small molecules and their surfaces can be decorated with multiple functionalities. However, selective targeting is still a challenge for translating ferritin-based nanomedicines into the clinic, especially for heterogeneous diseases such as cancer. Targeting peptides can be genetically fused onto the surface of a ferritin cage, forming peptide bunches on nanocages (PBNCs) that offer synergistic increases in binding avidity. Here, we utilized two sites of the ferritin monomer, the N-terminus and the loop between the fourth and fifth helices, which are exposed on the surface of the assembled 24-subunit ferritin cage, to ligate one or two types of peptides to achieve "super affinity" and bispecificity, respectively. PBNCs formed by ligation of the IL-4 receptor targeting peptide, AP1, to both sites (48AP1-PBNCs) tethered IL-4R, expressing tumor cells with greater affinity than did PBNCs with AP1 ligated to a single site (24AP1-PBNCs). Moreover, bispecific PBNCs containing 24 RGD peptides and 24 AP1 peptides (24RGD/24AP1-PBNCs) were capable of independently targeting cells expressing the corresponding receptors. Bispecific and superaffinity PBNCs could be useful for efficient targeting of ferritin-based therapeutic/diagnostic agents in a clinical setting. PMID- 26899207 TI - Entry of PIP3-containing polyplexes into MDCK epithelial cells by local apical basal polarity reversal. AB - The polarized architecture of epithelium presents a barrier to therapeutic drug/gene carriers, which is mainly due to a limited (apical) internalization of the carrier systems. The bacterium Pseudomonas aeruginosa invades epithelial cells by inducing production of apical phosphatidylinositol-3, 4, 5-triphosphate (PIP3), which results in the recruitment of basolateral receptors to the apical membrane. Since basolateral receptors are known receptors for gene delivery vectors, apical PIP3 may improve the internalization of such vectors into epithelial cells. PIP3 and nucleic acids were complexed by the cationic polymer polyethylenimine (PEI), forming PEI/PIP3 polyplexes. PEI/PIP3 polyplexes showed enhanced internalization compared to PEI polyplexes in polarized MDCK cells, while basolateral receptors were found to redistribute and colocalize with PEI/PIP3 polyplexes at the apical membrane. Following their uptake via endocytosis, PEI/PIP3 polyplexes showed efficient endosomal escape. The effectiveness of the PIP3-containing delivery system to generate a physiological effect was demonstrated by an essentially complete knock down of GFP expression in 30% of GFP-expressing MDCK cells following anti-GFP siRNA delivery. Here, we demonstrate that polyplexes can be successfully modified to mimic epithelial entry mechanisms used by Pseudomonas aeruginosa. These findings encourage the development of pathogen-inspired drug delivery systems to improve drug/gene delivery into and across tissue barriers. PMID- 26899208 TI - Transport of pyruvate into mitochondria is involved in methylmercury toxicity. AB - We have previously demonstrated that the overexpression of enzymes involved in the production of pyruvate, enolase 2 (Eno2) and D-lactate dehydrogenase (Dld3) renders yeast highly sensitive to methylmercury and that the promotion of intracellular pyruvate synthesis may be involved in intensifying the toxicity of methylmercury. In the present study, we showed that the addition of pyruvate to culture media in non-toxic concentrations significantly enhanced the sensitivity of yeast and human neuroblastoma cells to methylmercury. The results also suggested that methylmercury promoted the transport of pyruvate into mitochondria and that the increased pyruvate concentrations in mitochondria were involved in intensifying the toxicity of methylmercury without pyruvate being converted to acetyl-CoA. Furthermore, in human neuroblastoma cells, methylmercury treatment alone decreased the mitochondrial membrane potential, and the addition of pyruvate led to a further significant decrease. In addition, treatment with N acetylcysteine (an antioxidant) significantly alleviated the toxicity of methylmercury and significantly inhibited the intensification of methylmercury toxicity by pyruvate. Based on these data, we hypothesize that methylmercury exerts its toxicity by raising the level of pyruvate in mitochondria and that mitochondrial dysfunction and increased levels of reactive oxygen species are involved in the action of pyruvate. PMID- 26899210 TI - Perceptual similarity of visual patterns predicts dynamic neural activation patterns measured with MEG. AB - Perceptual similarity is a cognitive judgment that represents the end-stage of a complex cascade of hierarchical processing throughout visual cortex. Previous studies have shown a correspondence between the similarity of coarse-scale fMRI activation patterns and the perceived similarity of visual stimuli, suggesting that visual objects that appear similar also share similar underlying patterns of neural activation. Here we explore the temporal relationship between the human brain's time-varying representation of visual patterns and behavioral judgments of perceptual similarity. The visual stimuli were abstract patterns constructed from identical perceptual units (oriented Gabor patches) so that each pattern had a unique global form or perceptual 'Gestalt'. The visual stimuli were decodable from evoked neural activation patterns measured with magnetoencephalography (MEG), however, stimuli differed in the similarity of their neural representation as estimated by differences in decodability. Early after stimulus onset (from 50ms), a model based on retinotopic organization predicted the representational similarity of the visual stimuli. Following the peak correlation between the retinotopic model and neural data at 80ms, the neural representations quickly evolved so that retinotopy no longer provided a sufficient account of the brain's time-varying representation of the stimuli. Overall the strongest predictor of the brain's representation was a model based on human judgments of perceptual similarity, which reached the limits of the maximum correlation with the neural data defined by the 'noise ceiling'. Our results show that large-scale brain activation patterns contain a neural signature for the perceptual Gestalt of composite visual features, and demonstrate a strong correspondence between perception and complex patterns of brain activity. PMID- 26899209 TI - Unmasking local activity within local field potentials (LFPs) by removing distal electrical signals using independent component analysis. AB - Local field potentials (LFPs) are commonly thought to reflect the aggregate dynamics in local neural circuits around recording electrodes. However, we show that when LFPs are recorded in awake behaving animals against a distal reference on the skull as commonly practiced, LFPs are significantly contaminated by non local and non-neural sources arising from the reference electrode and from movement-related noise. In a data set with simultaneously recorded LFPs and electroencephalograms (EEGs) across multiple brain regions while rats perform an auditory oddball task, we used independent component analysis (ICA) to identify signals arising from electrical reference and from volume-conducted noise based on their distributed spatial pattern across multiple electrodes and distinct power spectral features. These sources of distal electrical signals collectively accounted for 23-77% of total variance in unprocessed LFPs, as well as most of the gamma oscillation responses to the target stimulus in EEGs. Gamma oscillation power was concentrated in volume-conducted noise and was tightly coupled with the onset of licking behavior, suggesting a likely origin of muscle activity associated with body movement or orofacial movement. The removal of distal signal contamination also selectively reduced correlations of LFP/EEG signals between distant brain regions but not within the same region. Finally, the removal of contamination from distal electrical signals preserved an event-related potential (ERP) response to auditory stimuli in the frontal cortex and also increased the coupling between the frontal ERP amplitude and neuronal activity in the basal forebrain, supporting the conclusion that removing distal electrical signals unmasked local activity within LFPs. Together, these results highlight the significant contamination of LFPs by distal electrical signals and caution against the straightforward interpretation of unprocessed LFPs. Our results provide a principled approach to identify and remove such contamination to unmask local LFPs. PMID- 26899211 TI - Replication of Han Chinese GWAS loci for schizophrenia via meta-analysis of four independent samples. AB - Schizophrenia is a highly heritable psychiatric disorder with unclear aetiology. Recent genome-wide association studies (GWAS) in European populations have reported numerous susceptibility variants, while GWAS in East Asians also identified several risk loci but with fewer independent replications. Here we focus on nine single nucleotide polymorphisms (SNPs) which have shown genome-wide significant associations with schizophrenia in previous Han Chinese GWAS, and we tend to replicate the associations in four independent samples of East Asian origin including a total of 3977 cases and 5589 controls. The results showed that rs10489202 in MPC2 (BRP44) is significantly associated with schizophrenia in these East Asian replication samples (one-tailed P=5.75*10(-3), OR=1.12), and further meta-analysis after including previous GWAS data yielded a genome-wide significant association (two-tailed P=1.11*10(-10), OR=1.19), adding further support for the involvement of this locus in the genetic risk of schizophrenia, and future studies regarding the underlying molecular mechanisms of the risk association are necessary. PMID- 26899212 TI - Cognitive insight is associated with cortical thickness in first-episode psychosis. AB - Compared to non-clinical subjects, people with psychosis show poor cognitive insight as reflected in low Self-Reflectiveness and high Self-Certainty. Neuroimaging studies have reported that 1) low Self-Reflectiveness is associated with volumetric reductions in ventrolateral prefrontal cortex (VLPFC), 2) higher Self-Certainty is associated with volumetric reductions in hippocampus, and 3) higher Self-Certainty is associated with fractional anisotropy in the fornix, in people with psychosis. The aims of the current study were to expand on this research by 1) performing an exploratory whole-brain cortical thickness analysis of the neural correlates of cognitive insight, to reveal whether regions outside the VLPFC are important for cognitive insight, and 2) to evaluate associations between cognitive insight and subfields of the hippocampus, which are distinct, interacting, and have different functions. We also aimed to replicate previous research documenting associations between cognitive insight and 3) total hippocampal volumes and 4) fornix fractional anisotropy. Fifteen people with a first-episode psychosis completed the Beck Cognitive Insight Scale and provided magnetic resonance and diffusion tensor imaging scans. Cortical thickness and hippocampal volumes were analyzed in FreeSurfer, and fornixfractional anisotropy was analyzed in Diffusion Toolkit/TrackVis. Higher Self-Reflectiveness and lower Self-Certainty significantly associated with thickness and thinness in VLPFC, respectively, as well as thickness and thinness in widespread frontal, parietal and temporal cortices. No associations emerged between Self-Reflectiveness or Self-Certainty and hippocampal total or sub-field volumes, or fornix fractional anisotropy. Results suggest that the neural correlates of cognitive insight involve a network of frontal, temporal and parietal brain regions. PMID- 26899213 TI - Correlation of Serum and Salivary Cytokines Level With Clinical Parameters in Metabolic Syndrome With Periodontitis. AB - BACKGROUND: Metabolic Syndrome (MS) and chronic oral condition (periodontitis [PD]) are state of inflammation. The study was conducted to determine alterations in serum and salivary cytokines level in MS and/or chronic PD in the North Indian population. MATERIALS AND METHODS: This cross-sectional study carried out in northern part of India. The study subjects of similar ethnicity were recruited according to International Diabetes Federation (IDF) criteria for MS, while chronic PD was diagnosed on the basis of packet depth and clinical attachment level. ELISA method was employed to assess cytokine level. All subjects were divided in four groups Gr A (MS + PD), B (MS), C (PD), and a control Gr D. RESULTS: The serum and salivary tumor necrosis factor alpha (TNF-alpha) level in Gr A, B, and C was significantly higher than Gr D (P < 0.05). Serum interleukin 10 (IL-10) level in Gr A, B, and C was lower than Gr D (P < 0.05), but this difference was not significant between Gr C and Gr D. Serum IL-10 level in Gr A was significantly lower than Gr C (P < 0.05). Salivary IL-10 level was not significantly altered in any group. CONCLUSIONS: Proinflammatory marker TNF-alpha has correlation with clinical parameters in patients of MS having PD. The study suggests level of salivary TNF-alpha may be utilized as a surrogate marker of MS and PD. PMID- 26899215 TI - [Visual quality needs to be improved in non-surgical optical correction]. AB - Optical correction is the basis of optometry. Optimized visual quality through optical correction is more challenging and more scientific as visual quality is becoming more closely related to social integration and development. There are many visual quality problems associated with various non-surgical optical correction methods in different aspects and degrees. This article discusses in depth some of the problems regarding optical correction with spectacles for different age groups, from children to seniors. The use of soft contact lenses, rigid gas-permeable contact lenses, and orthokeratology lenses is also evaluated. Moreover, some suggestions and recommendations on promoting visual quality through optical correction are provided. PMID- 26899214 TI - Evaluation of a faecal calprotectin care pathway for use in primary care. AB - BACKGROUND: National Institute for Health and Care Excellence have recommended faecal calprotectin (FC) testing as an option in adults with lower gastrointestinal symptoms for whom specialist investigations are being considered, if cancer is not suspected and it is used to support a diagnosis of inflammatory bowel disease (IBD) or irritable bowel syndrome. York Hospital and Vale of York Clinical Commissioning Group have developed an evidence-based care pathway to support this recommendation for use in primary care. It incorporates a higher FC cut-off value, a 'traffic light' system for risk and a clinical management pathway. OBJECTIVES: To evaluate this care pathway. METHODS: The care pathway was introduced into five primary care practices for a period of six months and the clinical outcomes of patients were evaluated. Negative and positive predictive values (NPV and PPV) were calculated. GP feedback of the care pathway was obtained by means of a web-based survey. Comparator gastroenterology activity in a neighbouring trust was obtained. RESULTS: The care pathway for FC in primary care had a 97% NPV and a 40% PPV. This was better than GP clinical judgement alone and doubled the PPV compared with the standard FC cut-off (250 mcg/g and were diagnosed by 'straight to test' colonoscopy within three weeks. The care pathway was considered helpful by GPs and delivered a higher diagnostic yield after secondary care referral (21%) than the conventional comparator pathway (5%). CONCLUSIONS: A care pathway for the use of FC that incorporates a higher cut-off value, a 'traffic light' system for risk and supports clinical decision making can be achieved safely and effectively. It maintains the balance between a high NPV and an acceptable PPV. A modified care pathway for the use of FC in primary care is proposed. PMID- 26899216 TI - [Update the concepts on visual correction and enhance the visual quality after corneal refractive surgery]. AB - In recent years, new technologies and ideas of modern ophthalmology and optometry have emerged. Based on the wavefront technology and its derivatives, the traditional concepts of refractive errors and vision correction have been redefined and supplemented. Human optical quality can be evaluated effectively and objectively. Moreover, the studies about the wavefront vision correction have shown preferable vision correction results. Application of these modern methods of wavefront refraction and correction offers important opportunities for better optical quality and visual performance in corneal refractive surgery. It also provides a foundation for creating novel clinical diagnosis and treatment options in vision correction. PMID- 26899217 TI - [Analysis of intraocular pressure measurement and the influencing factors after small incision lenticule extraction]. AB - OBJECTIVE: To discuss the accuracy of intraocular pressure (IOP) values measured after small incision lenticule extraction (SMILE), analyze the corneal biomechanical influencing factors of IOP measurement before and after SMILE, and regress the equation of IOP variation for estimating actual IOP. METHODS: In this clinical controlled study, 116 eyes (60 patients) with myopia and myopic astigmatism undergoing SMILE surgery were included. The ocular response analyzer, noncontact tonometer (NCT), and Pentacam system were used to measure the IOP preoperatively and at 3 months postoperatively, acquiring IOPg, IOPcc, NCT, Ehlers, Shah, Dresden, Orssengo, and Kohlhaas. The eight IOPs before and after surgery were analyzed with the paired t-testing. The Pearson correlation coefficient and Spearman correlation coefficient were used to evaluate the relationship between preoperative and postoperative IOPs and influencing factors. The regression analysis of IOP variation DeltaNCT and influencing factors was performed with the multiple linear regression analysis. RESULTS: The Shah program in Pentacam showed no difference between preoperative and postoperative IOP values (t=-0.08, P=0.940). There was significant difference in the other IOPs before and after SMILE (P<0.001). The preoperative IOPg, IOPcc, and NCT were correlated with the preoperative CRF (r=0.674, 0.248, 0.710,P<0.01). The preoperative IOPg, NCT, Ehlers, and Shah were correlated with the preoperative CCT (r=0.260, 0.259, -0.418, -0.245,P<0.01). A moderately positive correlation was shown between the preoperative and postoperative IOPs (r>=0.5,P=0.000). The postoperative IOPg, Ehlers, Shah, and Dresden were correlated with the postoperative CCT (P<0.05). The postoperative IOPg, NCT, Orssengo/Pye, and Kohlhaas were correlated with the postoperative CRF (r=0.707, 0.549, 0.276, 0.346,P<0.01). The postoperative IOPg, IOPcc, NCT, Ehlers, and Shah were correlated with the postoperative CH (r=0.296, -0.366, 0.270,-0.349, 0.197,P<0.05). The regression equation of IOP variation DeltaNCT and influencing factors was DeltaNCT=-4.618+ 0.389NCTpre-0.431SC (SC was the algebraic sum of sphere and cylinder,R(2)=0.366, P=0.000). CONCLUSIONS: The evaluation of IOP values after SMILE should not only take the preoperative IOP and postoperative CCT into consideration, but also the corneal biomechanics which may affect the postoperative IOP. IOPcc and Pentacam corrective IOPs are relatively reliable after SMILE. Among the five correction methods of Pentacam system, Shah program can be used as the first choice for correct IOP after SMILE. The regression equation of the postoperative corrected NCT, NCTpost corrected=NCTpost measured +0.389NCTpre-0.431SC-4.618, may be used to evaluate the real postoperative IOP in clinical practice. PMID- 26899218 TI - [The correlations between corneal sensation, tear meniscus volume, and tear film osmolarity after femtosecond laser-assisted LASIK]. AB - OBJECTIVE: To investigate the correlations between corneal sensation, tear meniscus volume, and tear film osmolarity after femtosecond laser-assisted LASIK (FS-LASIK) surgery. METHODS: In this prospective clinical study, 31 patients undergoing FS-LASIK for myopia were recruited. The upper and lower tear meniscus volumes (UTMV and LTMV) were measured by customized anterior segment optical coherence tomography, tear film osmolarity was measured by a TearLab Osmolarity test device, central corneal sensation was measured by a Cochet-Bonner esthesiometer preoperatively, at 1 week, 1 and 3 months postoperatively. Repeated measures analysis of variance was used to evaluate whether the tear film osmolarity, tear meniscus volume, and corneal sensation were changed after surgery. The correlations between these variables were analyzed by the Pearson correlation analysis. RESULTS: The tear film osmolarity was (310.03 +/- 16.48) mOsms/L preoperatively, (323.51 +/- 15.92) mOsms/L at 1 week, (319.93 +/- 14.27) mOsms/L at 1 month, and (314.97+/-12.91) mOsms/L at 3 months. The UTMV was (0.42+/-0.15), (0.25+/- 0.09), (0.30+/-0.11), and (0.35+/-0.09) MUL, respectively; the LTMV was (0.60+/-0.21),(0.37+/-0.08), (0.44+/- 0.14), and (0.52+/-0.17) MUL, respectively. The tear film osmolarity was significantly higher at 1 week and 1 month postoperatively compared with the baseline (P=0.001, 0.004), and reduced to the preoperative level at 3 months (P=0.573). The UTMV, LTMV, and corneal sensation values presented significant decreases at all postoperative time points (all P<0.05). The Pearson correlation analysis showed the postoperative UTMV had a weak relationship with corneal sensation at 1 week after surgery (r=0.356,P=0.005). There were significant correlations between the preoperative LTMV and corneal sensation at 1 week, 1 and 3 months (respectively, r=0.422, 0.366, 0.352;P=0.001, 0.004, 0.006). No significant correlations were found between the tear film osmolarity, tear meniscus volume, and corneal sensation after surgery (all P>0.05). CONCLUSION: The tear film osmolarity, tear meniscus volume, and corneal sensation became aggravated due to the FS-LASIK surgery procedures. There were significant correlations between the preoperative tear meniscus volume and recovery of corneal sensation early after surgery. A higher tear meniscus volume before surgery may contribute to a faster corneal sensation recovery. PMID- 26899219 TI - [Difficulties in lenticule extraction during small incision lenticule extraction with the continuous curvilinear lenticulerrhexis technique]. AB - OBJECTIVE: To investigate the incidence rate, classification, and management of difficulties in lenticule extraction during small incision lenticule extraction (SMILE) with the continuous curvilinear lenticulerrhexis (CCL) technique, and surgical safety and efficacy. METHODS: Retrospective study. A total of 342 continuous subjects (680 eyes) received surgical treatment by the same surgeon using the SMILE-CCL technique. The separation was performed only between the cap and anterior surface of the lenticule (8 to 2 o'clock) and at the edge between the cap and posterior surface of the lenticule (1 o'clock). The lenticule was then extracted in a clockwise motion using the CCL technique. Cases with lenticule extraction difficulties were observed through surgery videos. Classification and management of the difficulties were recorded. The rate of intact lenticule extraction was calculated. RESULTS: Twenty-two subjects (22 eyes) had lenticule extraction difficulties. The rate was 3.24%. No difficulty was found in side cut lifting. The microforceps grip loss occurred more than once in five eyes. It was difficult to separate the cap and anterior surface in 12 eyes. One eye had a microdefect in the margin of the lenticule. Five eyes were observed to have single side tearing of side cut. No eyes had double sides tearing of side cut. The microforceps were changed when grip loss occurred more than once. When there were separation difficulties, the pace of lenticule extraction was slowed down, with tearing through the tangential direction of the circle (clockwise). The conventional technique was used in three cases with severe difficulties. All lenticules were successfully extracted from the 22 eyes (100%). Uncorrected visual acuity was >=1.0 in all eyes at 1 day after surgery. The safety index (the ratio between best corrected visual acuity at 1 month and preoperatively) was 1.11. The efficacy index (the ratio between uncorrected visual acuity at 1 month and preoperative best corrected visual acuity) was 1.04. CONCLUSIONS: Difficulties in lenticule extraction occur during SMILE-CCL with a low incidence. Various difficulties can be managed with different techniques. There are no extra effects on surgical safety and efficacy. It is safe and effective to switch back to the conventional technique when severe lenticule extraction difficulties occur. PMID- 26899220 TI - [Clinical analysis of complications of LASIK using the WaveLight FS200 femtosecond laser]. AB - OBJECTIVE: To explore the incidence of intraoperative and early postoperative complications associated with the WaveLight FS200 femtosecond laser-assisted flap creation in LASIK surgery. METHODS: A consecutive series of 400 patients (786 eyes) who underwent LASIK using the WaveLight FS200 femtosecond laser from March 2011 to December 2012 were included in this retrospective study. Intraoperative and early postoperative complications were described and analyzed. RESULTS: The intraoperative complications included suction loss (two eyes, 0.25%), incomplete flap creation (one eye, 0.13%), severe opaque bubble layers (three eyes, 0.38%), anterior chamber gas bubbles (eight eyes, 1.02%), skip lines (12 eyes, 1.53%), and corneal epithelial defects (eight eyes, 1.02%). The early postoperative complications included canal bleeding (eight eyes, 1.02%), diffuse lamellar keratitis (23 eyes, 2.93%), haze (six eyes, 0.76% ), and flap dislocation (one eye, 0.13% ). CONCLUSIONS: Intraoperative and early postoperative complications of LASIK using the WaveLight FS200 were relatively mild. All patients could obtain satisfactory clinical results with proper treatment. PMID- 26899221 TI - [Objective assessment of comprehensive optical quality among adults at different ages]. AB - OBJECTIVE: To objectively assess and compare comprehensive optical quality among adults at different ages. METHODS: In this cross-sectional study, there were 432 subjects (432 eyes) aged from 20 to 70 years with best corrected visual acuity (BCVA) better than 4.9. If both eyes of a subject had equal BCVA, one eye was selected randomly. Otherwise, the eye with better BCVA was chosen. The patients were divided into 5 groups at an age interval of 10 years. The optical quality analysis system II (OQASII) was used to measure the following optical quality parameters: the modulation transfer function cutoff frequency (MTFcutoff), the Strehl ratio, three OQAS values (OV100%, OV20%, and OV9%), and the objective scatter index (OSI). Each optical quality parameter was compared among different groups by One-way ANOVA. RESULTS: In the groups of 20-29 years, 30-39 years, 40 49 years, 50-59 years, and 60-69 years, the MTFcutoff was (43.91+/-7.43), (40.93+/-9.92), (37.16+/-9.04), (36.69+/-7.87), and (28.52+/-8.31) cpd, respectively; the Strehl ratio was 0.26+/-0.06, 0.24+/-0.06, 0.20+/-0.05, 0.20+/ 0.04, and 0.16+/-0.04, respectively; the OV100% was 1.47+/-0.24, 1.36+/-0.33, 1.24+/-0.30, 1.22+/-0.26, and 0.96+/-0.28, respectively; the OV20% was 1.51+/ 0.33, 1.40+/-0.38, 1.22+/-0.36, 1.20+/-0.28, and 0.91+/-0.32, respectively; the OV9% was 1.14+/-0.26, 1.41+/-0.40, 1.20+/- 0.37, 1.18+/-0.28, and 0.89+/-0.28, respectively; the OSI was 0.42+/-0.24, 0.53+/-0.32, 0.54+/-0.34, 0.54+/-0.26, and 1.06+/-0.56, respectively. There were significant differences in the mean values of MTFcutoff, Strehl ratio, OV100%, and OV20% among groups (P<0.05), except for the groups of 40-49 years and 50-59 years (P>0.05). The OV9% was significantly different among groups (P<0.05), except for the groups of 20-29 years, 40-49 years, and 50-59 years (P>0.19). The OSI was also significantly different among groups (P<0.05), except for the groups of 30-39 years, 40-49 years, and 50-59 years (P>0.70). CONCLUSION: The comprehensive optical quality in the young healthy population is better than the old, except for a plateau in the middle aged population. PMID- 26899222 TI - [Qualitative analysis of the evaluation indicators and their related parameters of ametropic state]. AB - OBJECTIVE: To investigate the theoretical basis and practical limitations of the existing calculation formulas in the evaluation of ametropic state. METHODS: The evaluation indicators and their calculation parameters of ametropia were analyzed by using the reduced schematic model eye, the paraxial imaging principle, and the dimension laws. RESULTS: The existing formulas resulted from the reduced object vergence of object distance and image distance relation. Regarding the two measurement indicators of the existing formulas, diopter was misused for refractive power. "Ametropia degree" was a non-standard diction. Both of them were not suitable as the evaluation indicators. The outcomes of the existing formulas and their related plus or minus sign rules showed refractive corrections instead of refractive errors proper. For refractive errors, there was no suitable evaluation indicator. CONCLUSIONS: In the evaluation of ametropic state, there are fundamental problems in the existing formulas resulting from the reduced object vergence. The measurement indicators and their dimensional units are confused and misused. The calculation results refer to the refractive corrections only. The evaluation indicators for ametropia need to be further discussed. PMID- 26899223 TI - [The application of vector analysis for evaluation of astigmatism correction in the corneal refractive surgery]. AB - Since sixty percent of ametropes obtain astigmatism, which has influence on the visual quality, correcting the astigmatism is always the focus of concerns during visual correction procedures especially for the corneal refractive surgery. The postoperative spherical equivalent or residual cylindrical dioptors was used as quantitative index to evaluate the correction of astigmatism previously; however, such results neglect the effect of astigmatic axis shift on the treatment. Taking astigmatism as a vector parameter could describe the magnitude and direction of astigmatism accurately, thus it was increasingly applied in the evaluation of astigmatism correction. This paper reviews the present vector analysis methods, evaluation indexes and its application for the correction of astigmatism in the corneal refractive surgery. PMID- 26899224 TI - [Advance of femtosecond small incision lenticule extraction (SMILE) in clinic application]. AB - Femtosecond small incision lenticule extraction (SMILE) had been performed in clinic more than 5 years in China. With the gradual development of the technology, SMILE has caused more and more attention because of the remarkable clinical effect, micro incision, minimally invasive and refractive stability. The reuse of the refractive lenticule (RL) from SMILE has recently become extensive focus, which brings potential method to corneal refractive surgery from subtraction to addition. This review has clarified the technology of SMILE on the aspects of corneal refractive correct, the clinical effect of reuse the materials (RL), the basis of related research and the possible improvement in the future. PMID- 26899225 TI - [The research progress of straylight in human eyes]. AB - As an influencing factor of visual quality, straylight is a functional measure of the effect of light scatter across the retina. The phenomenon depends on the refractive index and the turbidity of the ocular media. This light scattering reduces the contrast of the image projected on the retina, and thus decreases the quality of vision. The review focuses on the concept and classification of straylight, and the relationship between straylight and visual quality. PMID- 26899226 TI - A dynamic look backward and forward. AB - The 2015 Gunther Laukien Prize recognized solution NMR studies of protein dynamics and thermodynamics. This Perspective surveys aspects of the development and application of NMR spin relaxation for investigations of protein flexibility and function over multiple time scales in solution. Methods highlighted include analysis of overall rotational diffusion, theoretical descriptions of R1rho relaxation, and molecular dynamics simulations to interpret NMR spin relaxation. Applications are illustrated for the zinc-finger domain Xfin-31, the calcium binding proteins calbindin D9k and calmodulin, and the bZip transcription factor of GCN4. PMID- 26899227 TI - Biochemical characterization of extra- and intracellular endoxylanse from thermophilic bacterium Caldicellulosiruptor kronotskyensis. AB - Caldicellulosiruptor kronotskyensis grows on lignocellulosic biomass by the catalysis of intrinsic glycoside hydrolase, and has potential application for consolidated bioprocessing. In current study, two predicted extra- (Xyn10A) and intracellular (Xyn10B) xylanase from C. kronotskyensis were comparatively characterized. Xyn10A and Xyn10B share GH10 catalytic domain with similarity of 41%, while the former contains two tandem N-terminus CBM22s. Xyn10A showed higher hydrolytic capability than Xyn10B on both beechwood xylan (BWX) and oat spelt xylan (OSX). Truncation mutation experiments revealed the importance of CBMs for hydrolytic activity, substrate binding and thermostability of Xyn10A.While the quantity of CBM was not directly related to bind and thermostability. Although CBM was considered to be crucial for substrate binding, Xyn10B and Xyn10A as well as truncations performed similar binding affinity to insoluble substrate OSX. Analysis of point mutation revealed similar key residues, Glu493, Glu601 and Trp658 for Xyn10A and Glu139, Glu247 and Trp305 for Xyn10B. Both Xyn10A and Xyn10B exhibited hydrolytic activity on the mechanical pretreated corncob. After pre-digested by Xyn10A or Xyn10B, the micropores inthe the mechanical pretreated corncob were observed, which enhanced the accessibility for cellulase. Compared with corncob hydrolyzed with cellulase alone, enhanced hydrolytic performance of was observed after pre-digestion by Xyn10A or Xyn10B. PMID- 26899228 TI - [Increase in genetically determined anemia as a result of migration in Germany]. AB - BACKGROUND: Due to the increasing numbers of migrants and asylum seekers, hemoglobinopathies and glucose-6-phosphate dehydrogenase deficiency are no longer rare diseases in Germany. As a result of the current migration movements these genetically determined diseases will gain in importance. METHODS: Following a literature search the prevalence of the original endemic regions was compiled and compared to the population composition based on statistical data on migrants, foreign residents and asylum seekers in Germany. RESULTS: In the endemic regions a prevalence of 40 % and sometimes higher have been found for glucose-6-phosphate dehydrogenase deficiency and hemoglobinopathies. The number of people arriving in Germany from these endemic regions is rapidly increasing. CONCLUSION: Due to the high number of asylum seekers arriving from Asian and African regions, genetic erythrocyte defects will gain importance in the differential diagnosis of anemia; therefore, medical education and training must incorporate heightened awareness of risks, diagnostics and therapy of these disease patterns. PMID- 26899229 TI - Cediranib, a pan-VEGFR inhibitor, and olaparib, a PARP inhibitor, in combination therapy for high grade serous ovarian cancer. AB - INTRODUCTION: An estimated 22,000 women are diagnosed annually with ovarian cancer in the United States. Initially chemo-sensitive, recurrent disease ultimately becomes chemoresistant and may kill ~14,000 women annually. Molecularly targeted therapy with cediranib (AZD2171), a vascular endothelial growth factor receptor (VEGFR)-1, 2, and 3 signaling blocker, and olaparib (AZD2281), a poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor, administered orally in combination has shown anti-tumor activity in the treatment of high grade serous ovarian cancer (HGSOC). This combination has the potential to change the treatment of HGSOC. AREAS COVERED: Preclinical and clinical studies of single agent cediranib and olaparib or their combination are reviewed. Data are presented from peer-reviewed published manuscripts, completed and ongoing early phase clinical trials registered in ClinicalTrials.gov, National Cancer Institute-sponsored clinical trials, and related recent abstracts. EXPERT OPINION: Advances in the treatment of HGSOC that improve progression-free and overall survival have proven elusive despite examination of molecularly targeted therapy. HGSOC patients with deleterious germline or somatic mutations in BRCA1 or BRCA2 (BRCAm) are most responsive to PARP inhibitors (PARPi). PARPi combined with angiogenesis inhibition improved anti-cancer response and duration in both BRCAm and BRCA wild type HGSOC patients, compared to olaparib single agent treatment, demonstrating therapeutic chemical and contextual synthetic lethality. PMID- 26899230 TI - GUIDING PRINCIPLES FOR GOOD PRACTICES IN HOSPITAL-BASED HEALTH TECHNOLOGY ASSESSMENT UNITS. AB - OBJECTIVES: Health technology assessment (HTA) carried out for policy decision making has well-established principles unlike hospital-based HTA (HB-HTA), which differs from the former in the context characteristics and ways of operation. This study proposes principles for good practices in HB-HTA units. METHODS: A framework for good practice criteria was built inspired by the EFQM excellence business model and information from six literature reviews, 107 face-to-face interviews, forty case studies, large-scale survey, focus group, Delphi survey, as well as local and international validation. In total, 385 people from twenty countries have participated in defining the principles for good practices in HB HTA units. RESULTS: Fifteen guiding principles for good practices in HB-HTA units are grouped in four dimensions. Dimension 1 deals with principles of the assessment process aimed at providing contextualized information for hospital decision makers. Dimension 2 describes leadership, strategy and partnerships of HB-HTA units which govern and facilitate the assessment process. Dimension 3 focuses on adequate resources that ensure the operation of HB-HTA units. Dimension 4 deals with measuring the short- and long-term impact of the overall performance of HB-HTA units. Finally, nine core guiding principles were selected as essential requirements for HB-HTA units based on the expertise of the HB-HTA units participating in the project. CONCLUSIONS: Guiding principles for good practices set up a benchmark for HB-HTA because they represent the ideal performance of HB-HTA units; nevertheless, when performing HTA at hospital level, context also matters; therefore, they should be adapted to ensure their applicability in the local context. PMID- 26899231 TI - CT colonography for the detection of nonpolypoid colorectal lesions A prospective series. AB - AIM: To determine the diagnostic accuracy of CT-colonography (CTC) for colorectal nonpolypoid lesions. MATERIALS AND METHODS: In the period 2010-2011, 51 out of 454 patients undergoing CTC received also optical colonoscopy (OC). Three human readers with high, intermediate and low expertise interpreted the images. Flat lesions were defined as 3 mm or less in height; laterally spreading type (LST) lesions were defined as nonpolypoid lesions with more than 10 mm lateral diameter. RESULTS: A total of 75 nonpolypoid colorectal lesions were identified in 21 patients: 43 type II-A low-grade adenomas, 2 type II-c Tis adenocarcinomas, 2 LST Tis adenocarcinomas, 24 nonadenomatous (hyperplastic) lesions and 4 LST infiltrating tumors (T1N0M0 in 2 cases and T2N0M0 in 2 cases). Per-lesion sensitivity and NPV were 44% and 80.5%, while per-patient sensitivity, specificity, PPV, NPV and accuracy were 80.9%, 93.7%, 89.5%, 88.2%, 88.7%. The readers with high and intermediate experience yielded significantly better diagnostic performances than reader with low experience (p =0.072 and p=0.030). All the infiltrating carcinomas and 75% of tis carcinomas were detected by all the readers. CONCLUSION: CTC showed a low per-lesion and an high per-patient diagnostic accuracy for all nonpolypoid colorectal lesions, but an high ability to detect nonpolypoid colorectal carcinomas. Diagnostic performances are strictly related to the reader experience. KEY WORDS: Adenoma, Colon cancer, Colonoscopy CT colonography, Non polypoid lesions, Screening. PMID- 26899232 TI - Biogenic Nanoparticles from Schwanniomyces occidentalis NCIM 3459: Mechanistic Aspects and Catalytic Applications. AB - When cells of Schwanniomyces occidentalis NCIM 3459 were incubated with 1 mM tetrachloroauric acid (HAuCl4) or silver nitrate (AgNO3), cell-associated nanoparticles were obtained. Their presence was confirmed by scanning electron microscope observations. The cell-free supernatant (CFS) of the yeast mediated the synthesis of gold nanoparticles. On account of the difficulties associated with the use of cell-bound nanoparticles, further work was restricted to extracellular nanoparticles. It was hypothesized that the CFS contained thermostable biomolecule(s) that mediated metal reduction reactions. Extraction of the CFS with chloroform/methanol (2:1) and subsequent separation by preparative thin layer chromatography led to the activity-guided purification of a glycolipid. The glycolipid was hydrolyzed and the glycone (glucose) and aglycone components (palmitic acid and oleic acid) were identified by gas chromatography-mass spectrometry. The purified glycolipid mediated the synthesis of gold and silver nanoparticles that were characterized by using an X-ray diffractometer and transmission electron microscope (TEM). The extracellular nanoparticles displayed catalytic activities and reduced 4-nitroaniline to benzene-1,4-diamine. This paper thus highlights nanoparticle synthesis by a hitherto unreported yeast culture, identifies the biomolecules involved in the process, and describes a potential application of the nanostructures. PMID- 26899233 TI - Facile Alkaline Lysis of Escherichia coli Cells in High-Throughput Mode for Screening Enzyme Mutants: Arylsulfatase as an Example. AB - Facile alkaline lysis of Escherichia coli cells in high-throughput (HTP) mode for screening enzyme mutants was tested with Pseudomonas aeruginosa arylsulfatase (PAAS). The alkaline lysis buffer was 1.0 M Tris-HCl at pH 9.0 plus 0.1 % Tween 20 and 2.0 mM 4-aminobenzamidine, mixed with cell suspension at 8:1 to 12:1 ratio for continuous agitation of mixtures in 96-well plates under room temperature; enzymatic activity in lysates was measured with 96-well microplate. PAAS activity tolerated final 0.1 % Tween-20. Individual clones were amplified for 12 h in 0.50 mL TB medium with 48-well plates to enhance the repeatability of induced expression. During continuous agitation of the mixture of cells and the lysis buffer, PAAS activities in lysates were steady from 3 to 9 h and comparable to sonication treatment but better than freezing-thawing. Coefficients of variation of activities of PAAS/mutants in lysates after treatment for 7 h reached ~22 %. The mutant M72Q had specific activity 2-fold of G138S. By HTP lysis of cells, M72Q was recognized as a positive mutant over G138S with the area under the curve of 0.873. Therefore, for enzymes tolerating concentrated alkaline buffers, the proposed alkaline lysis approach may be generally applicable for HTP lysis of host cells during directed evolution. PMID- 26899234 TI - A unique dual recognition hairpin probe mediated fluorescence amplification method for sensitive detection of uracil-DNA glycosylase and endonuclease IV activities. AB - Uracil-DNA glycosylase (UDG) and endonuclease IV (Endo IV) play cooperative roles in uracil base-excision repair (UBER) and inactivity of either will interrupt the UBER to cause disease. Detection of UDG and Endo IV activities is crucial to evaluate the UBER process in fundamental research and diagnostic application. Here, a unique dual recognition hairpin probe mediated fluorescence amplification method was developed for sensitively and selectively detecting UDG and Endo IV activities. For detecting UDG activity, the uracil base in the probe was excised by the target enzyme to generate an apurinic/apyrimidinic (AP) site, achieving the UDG recognition. Then, the AP site was cleaved by a tool enzyme Endo IV, releasing a primer to trigger rolling circle amplification (RCA) reaction. Finally, the RCA reaction produced numerous repeated G-quadruplex sequences, which interacted with N-methyl-mesoporphyrin IX to generate an enhanced fluorescence signal. Alternatively, for detecting Endo IV activity, the uracil base in the probe was first converted into an AP site by a tool enzyme UDG. Next, the AP site was cleaved by the target enzyme, achieving the Endo IV recognition. The signal was then generated and amplified in the same way as those in the UDG activity assay. The detection limits were as low as 0.00017 U mL(-1) for UDG and 0.11 U mL(-1) for Endo IV, respectively. Moreover, UDG and Endo IV can be well distinguished from their analogs. This method is beneficial for properly evaluating the UBER process in function studies and disease prognoses. PMID- 26899235 TI - Supramolecular Wiring of Benzo-1,3-chalcogenazoles through Programmed Chalcogen Bonding Interactions. AB - The high-yielding synthesis of 2-substituted benzo-1,3-tellurazoles and benzo-1,3 selenazoles through a dehydrative cyclization reaction has been reported, giving access to a large variety of benzo-1,3-chalcogenazoles. Exceptionally, these aromatic heterocycles proved to be very stable and thus very handy to form controlled solid-state organizations in which wire-like polymeric structures are formed through secondary N???Y bonding interactions (SBIs) engaging the chalcogen (Y=Se or Te) and nitrogen atoms. In particular, it has been shown that the recognition properties of the chalcogen centre at the solid state could be programmed by selectively barring one of its sigma-holes through a combination of electronic and steric effects exerted by the substituent at the 2-position. As predicted by the electrostatic potential surfaces calculated by quantum chemical modelling, the pyridyl groups revealed to be the stronger chalcogen bonding acceptors, and thus the best ligand candidate for programming the molecular organization at the solid state. In contrast, the thiophenyl group is an unsuitable substituent for establishing SBIs in this molecular system as it gives rise to chalcogen-chalcogen repulsion. The weaker chalcogen donor properties of the Se analogues trigger the formation of feeble N???Se contacts, which are manifested in similar solid-state polymers featuring longer nitrogen-chalcogen distances. PMID- 26899236 TI - An automated framework for 3D serous pigment epithelium detachment segmentation in SD-OCT images. AB - Pigment epithelium detachment (PED) is an important clinical manifestation of multiple chorioretinal diseases, which can cause loss of central vision. In this paper, an automated framework is proposed to segment serous PED in SD-OCT images. The proposed framework consists of four main steps: first, a multi-scale graph search method is applied to segment abnormal retinal layers; second, an effective AdaBoost method is applied to refine the initial segmented regions based on 62 extracted features; third, a shape-constrained graph cut method is applied to segment serous PED, in which the foreground and background seeds are obtained automatically; finally, an adaptive structure elements based morphology method is applied to remove false positive segmented regions. The proposed framework was tested on 25 SD-OCT volumes from 25 patients diagnosed with serous PED. The average true positive volume fraction (TPVF), false positive volume fraction (FPVF), dice similarity coefficient (DSC) and positive predictive value (PPV) are 90.08%, 0.22%, 91.20% and 92.62%, respectively. The proposed framework can provide clinicians with accurate quantitative information, including shape, size and position of the PED region, which can assist clinical diagnosis and treatment. PMID- 26899237 TI - Familial Mutations and Post-translational Modifications of UCH-L1 in Parkinson's Disease and Neurodegenerative Disorders. AB - Parkinson's disease (PD) is one of the most common progressive neurodegenerative disorders in modern society. The disease involves many genetic risk factors as well as a sporadic pathogenesis that is age- and environment-dependent. Of particular interest is the formation of intra-neural fibrillar aggregates, namely Lewy bodies (LBs), the histological hallmark of PD, which results from aberrant protein homeostasis or misfolding that results in neurotoxicity. A better understanding of the molecular mechanism and composition of these cellular inclusions will help shed light on the progression of misfolding-associated neurodegenerative disorders. Ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) is found to co-aggregate with alpha-synuclein (alphaS), the major component of LBs. Several familial mutations of UCH-L1, namely p.Ile93Met (p.I93M), p.Glu7Ala (p.E7A), and p.Ser18Tyr (p.S18Y), are associated with PD and other neurodegenerative disorders. Here, we review recent progress and recapitulate the impact of PD-associated mutations of UCH-L1 in the context of their biological functions gleaned from biochemical and biophysical studies. Finally, we summarize the effect of these genetic mutations and post-translational modifications on the association of UCHL1 and PD in terms of loss of cellular functions or gain of cellular toxicity. PMID- 26899238 TI - Inhibitory effects of Leonurus sibiricus on weight gain after menopause in ovariectomized and high-fat diet-fed mice. AB - Leonurus sibiricus, also called motherwort, is a well-known functional food and medicinal herb. It has been known to possess beneficial properties for women's health, especially for aged women. Estrogen deficiency in the menopause could induce lipid metabolic abnormalities in body fat, resulting in obesity. In this study, the inhibitory effects of L. sibiricus on obesity after the menopause were investigated. Female C57BL/6 mice were ovariectomized and fed high-fat diet (HFD) for 12 weeks. Following an induction period, aqueous extracts of L. sibiricus (LS) were orally administrated for 6 weeks. The body, uterine, and visceral fat weights were measured immediately after the animals were killed. Histological analysis was performed to monitor fat and liver. Serum levels of glucose, triglyceride, total cholesterol, and LDL-cholesterol were evaluated. In addition, the expression of lipases was analyzed. Total body weight was significantly decreased by LS treatment. Histological changes in adipocyte size were shown along with a decrease of visceral fat weight in the LS-treated group. In addition, the fat infiltration of liver was reduced by LS administration. LS treated mice experienced decreases of serum triglyceride, total cholesterol, and LDL-cholesterol levels. The expression of HSL and ATGL was significantly increased by LS treatment. These results suggest that LS could regulate the lipid metabolism via an increase of lipases expression in ovariectomized and HFD-fed mice. LS might be a novel candidate for a functional food to inhibit weight gain after the menopause. PMID- 26899239 TI - Enhanced anti-immobility effects of Sanggenon G isolated from the root bark of Morus alba combined with the alpha2-antagonist yohimbine in the rat forced swim test. AB - In this study, we aimed to determine whether Sanggenon G, an active compound isolated from the root bark of Morus alba, exhibited enhanced anti-immobility activity with the addition of the alpha2-antagonist yohimbine in rats subjected to forced swim test (FST)-induced depression. Fluoxetine (a selective serotonin reuptake inhibitor) treatment in rats reduced the immobility time, and pretreatment with yohimbine significantly enhanced the antidepressant-like behavior of fluoxetine at 5, 10 and 20 mg/kg. Similarly, Sanggenon G significantly decreased the immobility time, reducing immobility by a maximum of 43.9 % when treated at a dose of 20 mg/kg. Furthermore, pretreatment with yohimbine significantly enhanced the antidepressant-like behavior of Sanggenon G at 5 and 10 mg/kg. Our findings suggest that the antidepressant-like effect of Sanggenon G could be facilitated by concomitant use of the alpha2-antagonist. Further studies are needed to evaluate the potential of Sanggenon G as an alternative therapeutic approach for the treatment of depression. PMID- 26899240 TI - Lucidumol C, a new cytotoxic lanostanoid triterpene from Ganoderma lingzhi against human cancer cells. AB - A new oxygenated lanostane-type triterpene, named lucidumol C, together with six known compounds, was isolated from the chloroform extract of the fruiting bodies of Ganoderma lingzhi. Structures were established based on extensive spectroscopic and chemical studies. Potential cytotoxic activities of the isolated compounds were evaluated against human colorectal carcinoma (HCT-116, Caco-2), human liver carcinoma (HepG2), and human cervical carcinoma (HeLa) cell lines using WST-1 reagent. Selectivity was evaluated using normal human fibroblast cells (TIG-1 and HF19). Among the compounds, lucidumol C showed potent selective cytotoxicity against HCT-116 cells with an IC50 value of 7.86 +/- 4.56 uM and selectivity index (SI) >10 with remarkable cytotoxic activities against Caco-2, HepG2 and HeLa cell lines. PMID- 26899241 TI - Disparity in Frontal Lobe Connectivity on a Complex Bimanual Motor Task Aids in Classification of Operator Skill Level. AB - Objective metrics of technical performance (e.g., dexterity, time, and path length) are insufficient to fully characterize operator skill level, which may be encoded deep within neural function. Unlike reports that capture plasticity across days or weeks, this articles studies long-term plasticity in functional connectivity that occurs over years of professional task practice. Optical neuroimaging data are acquired from professional surgeons of varying experience on a complex bimanual coordination task with the aim of investigating learning related disparity in frontal lobe functional connectivity that arises as a consequence of motor skill level. The results suggest that prefrontal and premotor seed connectivity is more critical during naive versus expert performance. Given learning-related differences in connectivity, a least-squares support vector machine with a radial basis function kernel is employed to evaluate skill level using connectivity data. The results demonstrate discrimination of operator skill level with accuracy >=0.82 and Multiclass Matthew's Correlation Coefficient >=0.70. Furthermore, these indices are improved when local (i.e., within-region) rather than inter-regional (i.e., between region) frontal connectivity is considered (p = 0.002). The results suggest that it is possible to classify operator skill level with good accuracy from functional connectivity data, upon which objective assessment and neurofeedback may be used to improve operator performance during technical skill training. PMID- 26899242 TI - Reproducibility of the QT-variability index in individuals with spinal cord injury. AB - PURPOSE: To examine the day-to-day reproducibility of the QT-variability index (QTVI) and the QT-apex variability index (QTaVI) in individuals with spinal cord injury (SCI). METHODS: Ten individuals with SCI participated in the current study (C2-T10; AIS A-D; 8.6 +/- 7.8 years post-injury). On two occasions, with a 10-day interval, a 10-minute resting electrocardiogram was obtained from each participant. The QTVI and QTaVI were analyzed from 256 electrocardiographic beats from all participants, and a separate analysis was performed on those with injuries above the 4th thoracic level. An intraclass correlation coefficient (ICC) test was performed to measure day-to-day reproducibility of these measures and a Bland-Altman test was performed on all participants in order to examine the skewness of the measures. RESULTS: The reproducibility values were found to be high for both the QTVI (all participants: R=0.892; above T4: R=0.893) and the QTaVI (all participants: R=0.908; above T4: R=0.915). In addition, the reproducibility of QTVI and QTaVI did not appear to be skewed as indicated by Bland-Altman plots. CONCLUSION: Both the QTVI and the QTaVI may be used as reproducible means of assessing cardiac autonomic function in individuals with SCI. Further, a reduction in cardiac sympathetic regulation after high thoracic and cervical level SCI does not appear to influence the day-to-day reproducibility of these measures. PMID- 26899243 TI - Substituent Effects on the Photodeprotection Reactions of Selected Ketoprofen Derivatives in Phosphate Buffered Aqueous Solutions. AB - Photodeprotection is an important reaction that has been attracting broad interest for use in a variety of applications. Recent advances in ultrafast and vibrational time-resolved spectroscopies can facilitate obtaining data to help unravel the reaction mechanisms involving in the photochemical reactions of interest. The kinetics and reaction mechanisms for the photodeprotection reactions of ketoprofen derivatives containing three different substituents (ibuprofen, Br and I) were investigated by femtosecond transient absorption (fs TA) and nanosecond time-resolved resonance Raman (ns-TR(3)) spectroscopy methods in phosphate buffered solutions (PBS). Fs-TA allows us to detect the decay kinetics of the triplet species as the key precursor for formation of a carbanion species for three different substituents attached to ketoprofen. To characterize the structural and electronic properties of the corresponding carbanion and triplet intermediates, TR(3) spectroscopic experiments were conducted. The transient spectroscopy work reveals that the different substituents affect the photodecarboxylation reaction to produce carbon dioxide which in turn influences the generation of the carbanion species which determines the rate of the photorelease of the functional groups attached on the ketoprofen parent molecule. The fingerprint TR(3) spectroscopy results suggest that ketoprofen derivatives may be deactivated to produce a triplet carbanion when increasing the atom mass of the halogen atoms. PMID- 26899244 TI - Use of indirect lymphography to identify sentinel lymph node in dogs: a pilot study in 30 tumours. AB - This study reports the clinical value of sentinel lymph node (SLN) mapping with indirect lymphography (IL) using iodized oil (IO) as a marker injected preoperatively around the site of the primary tumour and radiography or tomodensitometry for imaging. Surgical extirpation of the node was performed following peritumoural injection of methylene blue (MB). Twenty nine dogs affected by 30 palpable solid tumours were prospectively studied. SLNs were identified by IL in 96.6% of the IL studies. IL followed by MB studies were performed in 25 dogs (26 studies). In these studies, agreement between IL and MB was observed in 84.6%. One dog had a minor complication following IO injection. This protocol represents an attractive alternative to scintigraphy for SLN mapping. This less technically demanding protocol may provide a wider access to SLN identification for application in veterinary oncology. PMID- 26899246 TI - The Relationship Between Focused Attention Meditation Practice Habits, Psychological Symptoms, and Quality of Life. AB - This study examined the relationship between focused attention meditation practice habits, psychological symptoms, and quality of life. The participants were 30 adults from New York, NY, practicing Ananda Marga spirituality. They were administered the Symptom Check List-90-R and the Quality of Life Index. The findings pointed out while Ananda Marga meditation practice habits were not associated with improvements in psychological symptoms, longer years in meditation practice was associated with improvements in overall, social and psychological/spiritual quality of life. Longer periods of meditation practice per session were related to lower levels of overall quality of life and economic quality of life. PMID- 26899245 TI - Current status of PET imaging in Huntington's disease. AB - PURPOSE: To review the developments of recent decades and the current status of PET molecular imaging in Huntington's disease (HD). METHODS: A systematic review of PET studies in HD was performed. The MEDLINE, Web of Science, Cochrane and Scopus databases were searched for articles in all languages published up to 19 August 2015 using the major medical subject heading "Huntington Disease" combined with text and key words "Huntington Disease", "Neuroimaging" and "PET". Only peer reviewed, primary research studies in HD patients and premanifest HD carriers, and studies in which clinical features were described in association with PET neuroimaging results, were included in this review. Reviews, case reports and nonhuman studies were excluded. RESULTS: A total of 54 PET studies were identified and analysed in this review. Brain metabolism ([(18)F]FDG and [(15)O]H2O), presynaptic ([(18)F]fluorodopa, [(11)C]beta-CIT and [(11)C]DTBZ) and postsynaptic ([(11)C]SCH22390, [(11)C]FLB457 and [(11)C]raclopride) dopaminergic function, phosphodiesterases ([(18)F]JNJ42259152, [(18)F]MNI-659 and [(11)C]IMA107), and adenosine ([(18)F]CPFPX), cannabinoid ([(18)F]MK-9470), opioid ([(11)C]diprenorphine) and GABA ([(11)C]flumazenil) receptors were evaluated as potential biomarkers for monitoring disease progression and for assessing the development and efficacy of novel disease-modifying drugs in premanifest HD carriers and HD patients. PET studies evaluating brain restoration and neuroprotection were also identified and described in detail. CONCLUSION: Brain metabolism, postsynaptic dopaminergic function and phosphodiesterase 10A levels were proven to be powerful in assessing disease progression. However, no single technique may be currently considered an optimal biomarker and an integrative multimodal imaging approach combining different techniques should be developed for monitoring potential neuroprotective and preventive treatment in HD. PMID- 26899248 TI - Sugar does not affect the bending and tilt moduli of simple lipid bilayers. AB - The diffuse X-ray scattering method has been applied to samples composed of SOPC, DOPC, DMPC, and POPC with added sugar, either sucrose, glucose, fructose, maltose, or trehalose. Several sugar concentrations in the range 200-500 mM were investigated for each of the lipid/sugar samples. We observed no systematic change in the bending modulus KC or in the tilt modulus Ktheta with increasing sugar concentration. The average values of both these moduli were the same as those of the respective pure lipid controls within statistical uncertainty of 2%. These results are inconsistent with previous reports of sugar concentration dependent values of KC. PMID- 26899247 TI - Akt attenuates apoptotic death through phosphorylation of H2A under hydrogen peroxide-induced oxidative stress in PC12 cells and hippocampal neurons. AB - Although the essential role of protein kinase B (PKB)/Akt in cell survival signaling has been clearly established, the mechanism by which Akt mediates the cellular response to hydrogen peroxide (H2O2)-induced oxidative stress remains unclear. We demonstrated that Akt attenuated neuronal apoptosis through direct association with histone 2A (H2A) and phosphorylation of H2A at threonine 17. At early time points during H2O2 exposure of PC12 cells and primary hippocampal neurons, when the cells can tolerate the level of DNA damage, Akt was activated and phosphorylated H2A, leading to inhibition of apoptotic death. At later time points, Akt delivered the NAD(+)-dependent protein deacetylase Sirtuin 2 (Sirt 2) to the vicinity of phosphorylated H2A in response to irreversible DNA damage, thereby inducing H2A deacetylation and subsequently leading to apoptotic death. Ectopically expressed T17A-substituted H2A minimally interacted with Akt and failed to prevent apoptosis under oxidative stress. Thus Akt-mediated H2A phosphorylation has an anti-apoptotic function in conditions of H2O2-induced oxidative stress in neurons and PC12 cells. PMID- 26899249 TI - Trefoil factor 3 shows anti-inflammatory effects on activated microglia. AB - Microglial cells are a major source of pro-inflammatory cytokines during central nervous system (CNS) inflammation. They can develop a pro-inflammatory M1 phenotype and an anti-inflammatory M2 phenotype. Shifting the phenotype from M1 to M2 might be an important mechanism to overcome CNS inflammation and to prevent or reduce neuronal damage. Here, we demonstrate that the anti-inflammatory protein trefoil factor 3 (TFF3) is secreted by astrocytes and that its transcription is significantly reduced after incubation with lipopolysaccharide (LPS). Moreover, we demonstrate that microglial cells cultured in the presence of TFF3 show reduced expression and secretion of pro-inflammatory cytokines after LPS stimulation. PMID- 26899251 TI - Role of Notch signaling in granulosa cell proliferation and polyovular follicle induction during folliculogenesis in mouse ovary. AB - In the fetal mouse ovary, oocytes are connected by an intercellular bridge and form germ cell cysts. Folliculogenesis begins after birth. To study the role of Notch signaling in folliculogenesis, double-immunohistochemical localization of laminin and Ki-67 was performed in mouse ovaries from embryonic day 17.5 (E17.5) to postnatal day 4 (P4). Most cysts and follicles contained Ki-67-negative cells; however, a few Ki-67-positive cells were present in cysts from E17.5 through P4, indicating that a small number of pre-granulosa cells continue to proliferate during folliculogenesis. To examine the effects of an inhibitor of Notch signaling (DAPT) and a synthetic estrogen (diethylstilbestrol [DES]) on folliculogenesis, an organ-culture system was established. The numbers of cysts, primordial follicles (PrFs) and primary follicles were unchanged by DES, whereas the total number of PrFs and of PrFs with Ki-67-negative cells was reduced by DAPT. In organ-cultured neonatal ovaries, only DAPT treatment increased degenerating cells defined as oocytes. On the contrary, the number of polyovular follicles (PFs) and the PF incidence were significantly increased in ovaries organ-cultured with DES at day 20 post-grafting. In organ-cultured fetal and neonatal ovaries, DAPT reduced Notch 3 and Hey2 mRNAs, whereas DES increased Hey2 mRNA. These results suggest that Notch signaling in fetal ovaries is involved with PrF assembly by the regulation of oocyte survival rather than by cell proliferation. In PF induction, as a result of the disruption of interactions between oocytes and pre-granulosa cells, DES and Notch signaling act independently. PMID- 26899250 TI - Cyclophilin A is a new M cell marker of bovine intestinal epithelium. AB - Microfold (M) cells in the follicle-associated epithelium (FAE) of Peyer's patches contribute to the mucosal immune response by the transcytosis of microorganisms. The mechanism by which M cells take up microorganisms, and the functional proteins by which they do this, are not clear. In order to explore one such protein, we developed a 2H5-F3 monoclonal antibody (2H5-F3 mAb) through its binding to bovine M cells, and identified the antibody reactive molecule as cyclophilin A (Cyp-A). The localization patterns of Cyp-A were very similar to the localization pattern of cytokeratin (CK) 18-positive M cells. Cyp-A was identified at the luminal surface of CK18-positive M cells in bovine jejunal and ileal FAE. The membranous localization of Cyp-A in the bovine intestinal cell line (BIE cells) increased as cells differentiated toward M cells, as determined by flow cytometry analysis. Additionally, BIE cells released Cyp-A to the extracellular space and the differentiation of BIE cells to M cells increased the secretion of Cyp-A, as determined by western blotting. Accordingly, Cyp-A may be localized in M cells in the small intestinal epithelium of cattle. The rise of the membranous localization and secretion of Cyp-A by differentiation toward M cells indicates that Cyp-A has an important role in the function of M cells. While Cyp-A of the M cell membrane may contribute to the uptake of viruses with peptidyl-prolyl cis-trans isomerase activity, in the extracellular space Cyp-A may work as a chemokine and contribute to the distribution of immuno-competent cells. PMID- 26899252 TI - Presence of gonadotropin-releasing hormone-like peptide in the central nervous system and reproductive organs of the male blue swimming crab, Portunus pelagicus, and its effect on spermatogenesis. AB - Our previous studies have demonstrated that lamprey gonadotropin-releasing hormone-III (lGnRH-III)-like peptide occurs in the central nervous system (CNS) of decapod crustaceans (Macrobrachium rosenbergii, Penaeus monodon, Portunus pelagicus), and that lGnRH-III is the most potent in stimulating ovarian maturation compared with other GnRH isoforms. In this study, we examined the localization of lGnRH-III-like peptide in the CNS and male reproductive organs of the blue swimming crab by using anti-lGnRH-III as a probe. In the brain, lGnRH III immunoreactivity (-ir) was detected in neurons of clusters 6, 10, 11, 14/15, 16, and 17 and in many neuropils. In the subesophageal ganglion, lGnRH-III-ir was present in neurons of the dorso-lateral and ventro-medial clusters. In the thoracic ganglia, lGnRH-III-ir was observed in the large-sized neurons between the thoracic neuropils and in the ventromedial cluster of the abdominal ganglia. In the testis, lGnRH-III-ir was detected in nurse cells, hemocytes, spermatids 2, and the outer and inner zones of the acrosomes of spermatozoa. Bioassay showed that lGnRH-III significantly increased the testis-somatic index, the percentage of late stages of seminiferous tubules (stages VII-IX), the diameter of the seminiferous tubules, and the number of BrdU-labeled early germ cells compared with the control groups. Thus, lGnRH-III-like peptide exists in the male crab and possibly enhances germ cell proliferation and maturation in the testes, leading to increased sperm production. PMID- 26899253 TI - Calcium buffer proteins are specific markers of human retinal neurons. AB - Ca(2+)-buffer proteins (CaBPs) modulate the temporal and spatial characteristics of transient intracellular Ca(2+)-concentration changes in neurons in order to fine-tune the strength and duration of the output signal. CaBPs have been used as neurochemical markers to identify and trace neurons of several brain loci including the mammalian retina. The CaBP content of retinal neurons, however, varies between species and, thus, the results inferred from animal models cannot be utilised directly by clinical ophthalmologists. Moreover, the shortage of well preserved human samples greatly impedes human retina studies at the cellular and network level. Our purpose has therefore been to examine the distribution of major CaBPs, including calretinin, calbindin-D28, parvalbumin and the recently discovered secretagogin in exceptionally well-preserved human retinal samples. Based on a combination of immunohistochemistry, Neurolucida tracing and Lucifer yellow injections, we have established a database in which the CaBP marker composition can be defined for morphologically identified cell types of the human retina. Hence, we describe the full CaBP make-up for a number of human retinal neurons, including HII horizontal cells, AII amacrine cells, type-1 tyrosine hydroxylase-expressing amacrine cells and other lesser known neurons. We have also found a number of unidentified cells whose morphology remains to be characterised. We present several examples of the colocalisation of two or three CaBPs with slightly different subcellular distributions in the same cell strongly suggesting a compartment-specific division of labour of Ca(2+)-buffering by CaBPs. Our work thus provides a neurochemical framework for future ophthalmological studies and renders new information concerning the cellular and subcellular distribution of CaBPs for experimental neuroscience. PMID- 26899254 TI - Professional medical writing support and the quality of randomised controlled trial reporting: a cross-sectional study. AB - OBJECTIVES: Authors may choose to work with professional medical writers when writing up their research for publication. We examined the relationship between medical writing support and the quality and timeliness of reporting of the results of randomised controlled trials (RCTs). DESIGN: Cross-sectional study. STUDY SAMPLE: Primary reports of RCTs published in BioMed Central journals from 2000 to 16 July 2014, subdivided into those with medical writing support (n=110) and those without medical writing support (n=123). MAIN OUTCOME MEASURES: Proportion of items that were completely reported from a predefined subset of the Consolidated Standards of Reporting Trials (CONSORT) checklist (12 items known to be commonly poorly reported), overall acceptance time (from manuscript submission to editorial acceptance) and quality of written English as assessed by peer reviewers. The effect of funding source and publication year was examined. RESULTS: The number of articles that completely reported at least 50% of the CONSORT items assessed was higher for those with declared medical writing support (39.1% (43/110 articles); 95% CI 29.9% to 48.9%) than for those without (21.1% (26/123 articles); 95% CI 14.3% to 29.4%). Articles with declared medical writing support were more likely than articles without such support to have acceptable written English (81.1% (43/53 articles); 95% CI 67.6% to 90.1% vs 47.9% (23/48 articles); 95% CI 33.5% to 62.7%). The median time of overall acceptance was longer for articles with declared medical writing support than for those without (167 days (IQR 114.5-231 days) vs 136 days (IQR 77-193 days)). CONCLUSIONS: In this sample of open-access journals, declared professional medical writing support was associated with more complete reporting of clinical trial results and higher quality of written English. Medical writing support may play an important role in raising the quality of clinical trial reporting. PMID- 26899255 TI - Direct His-Bundle Pacing Improved Left Ventricular Function and Remodelling in a Biventricular Pacing Nonresponder. AB - The optimal pacing modality after atrioventricular junction (AVJ) ablation remains unclear. Herein, we describe the case of a heart failure patient who had AVJ ablation for chronic atrial fibrillation and received a cardiac resynchronization therapy defibrillator device. Because of the lack of clinical response to biventricular pacing, the device was revised with the addition of direct His bundle pacing, which resulted in significant improvement in functional status and left ventricular indices. This case illustrated direct His bundle pacing as an alternative for conventional biventricular pacing in some cardiac resynchronization therapy nonresponders who undergo AVJ ablation for atrial fibrillation and have an intact distal conduction system. PMID- 26899256 TI - Don't throw away the champagne with the cork-age at first drink revisited. PMID- 26899257 TI - Cerebral amyloid-beta accumulation and deposition following traumatic brain injury--A narrative review and meta-analysis of animal studies. AB - Traumatic brain injury (TBI) increases the risk of neurodegenerative disorders many years post-injury. However, molecular mechanisms underlying the relationship between TBI and neurodegenerative diseases, such as Alzheimer's disease (AD), remain to be elucidated. Nevertheless, previous studies have demonstrated a link between TBI and increased amyloid-beta (Abeta), a protein involved in AD pathogenesis. Here, we review animal studies that measured Abeta levels following TBI. In addition, from a pool of initially identified 1209 published papers, we examined data from 19 eligible animal model studies using a meta-analytic approach. We found an acute increase in cerebral Abeta levels ranging from 24h to one month following TBI (overall log OR=2.97 +/- 0.40, p<0.001). These findings may contribute to further understanding the relationship between TBI and future dementia risk. The methodological inconsistencies of the studies discussed in this review suggest the need for improved and more standardised data collection and study design, in order to properly elucidate the role of TBI in the expression and accumulation of Abeta. PMID- 26899258 TI - Clinical trials of antiangiogenic therapy for hepatocellular carcinoma. AB - Angiogenesis is a promising therapeutic target to inhibit tumor growth. This review summarizes data from clinical trials of antiangiogenic agents in hepatocellular carcinoma. A systematic search of PubMed was performed to identify clinical trials of specific antiangiogenic agents in hepatocellular carcinoma treatment, particularly phase III trials involving treatment guidelines for advanced hepatocellular carcinoma. Sorafenib is the only systemic drug approved for the treatment of advanced hepatocellular carcinoma. Two large-scale, randomized phase III trials using sorafenib involving patients with unresectable HCC showed a significant survival benefit compared with placebo control groups. However, subsequent phase III trials of antiangiogenic agents in hepatocellular carcinoma have failed to improve survival compared with standard treatment protocols using sorafenib. The efficacy of antiangiogenic agents in combination with other drugs, transarterial chemoembolization, and surgical resection is currently being investigated. Future research is expected to optimize antiangiogenic therapies in combination with standard treatment with sorafenib. PMID- 26899260 TI - Cognitive flexibility, heart rate variability, and resilience predict fine grained regulation of arousal during prolonged threat. AB - Emotion regulation in the ongoing presence of a threat is essential for adaptive behavior. Threatening situations change over time and, as a consequence, require a fine-tuned, dynamic regulation of arousal to match the current state of the environment. Constructs such as cognitive flexibility, heart rate variability, and resilience have been proposed as resources for adaptive emotion regulation, especially in a moment-to-moment fashion. Nevertheless, none of these constructs has been empirically related to the dynamic regulation of arousal as it unfolds over the course of a prolonged threatening episode. Here, we do so by placing participants in a threatening and evolving immersive virtual environment called Room 101, while recording their skin conductance. Subsequently, participants rated their subjective arousal continuously over the course of the experience. Participants who had shown greater cognitive flexibility in a separate task (i.e., fewer task-switching costs when switching to evaluating the valence of positive stimuli) showed better regulation of physiological arousal (skin conductance level), during less-threatening phases of Room 101. Individuals with higher trait resilience and individuals with higher resting heart rate variability showed more regulation in terms of their subjective arousal experience. The results indicate that emotional, cognitive, and physiological flexibility support nuanced adaptive regulation of objective and experienced arousal in the ongoing presence of threats. Furthermore, the results indicate that these forms of flexibility differentially affect automatic and objective versus reflective and subjective processes. PMID- 26899259 TI - PD-1/PD-L1 blockade in cancer treatment: perspectives and issues. AB - Recent studies showed that tumor cells 'edit' host immunity in several ways to evade immune defenses in the tumor microenvironment. This phenomenon is called "cancer immune escape." One of the most important components in this system is an immunosuppressive co-signal (immune checkpoint) mediated by the PD-1 receptor and its ligand, PD-L1. PD-1 is mainly expressed on activated T cells, whereas PD-L1 is expressed on several types of tumor cells. Preclinical studies have shown that inhibition of the interaction between PD-1 and PD-L1 enhances the T-cell response and mediates antitumor activity. Several clinical trials of PD-1/PD-L1 signal blockade agents have exhibited dramatic antitumor efficacy in patients with certain types of solid or hematological malignancies. In this review, we highlight recent clinical trials using anti-PD-1 or anti-PD-L1 antibodies against several types of malignancies, including a trial conducted in our department, and describe the clinical perspectives and issues regarding the PD-1/PD-L1 blockade in cancer treatment. PMID- 26899261 TI - No-Report and Report-Based Paradigms Jointly Unravel the NCC: Response to Overgaard and Fazekas. PMID- 26899262 TI - Elevated Carboxyhaemoglobin Concentrations by Pulse CO-Oximetry is Associated with Severe Aluminium Phosphide Poisoning. AB - In pulse CO-oximetry of aluminium phosphide (ALP)-poisoned patients, we discovered that carboxyhaemoglobin (CO-Hb) level was elevated. We aimed to determine whether a higher CO level was detected in patients with severe ALP poisoning and if this could be used as a prognostic factor in these patients. In a prospective case-control study, 96 suspected cases of ALP poisoning were evaluated. In the ALP-poisoned group, demographic characteristics, gastric and exhalation silver nitrate test results, average CO-Hb saturation, methaemoglobin saturation, and blood pressure and blood gas analysis until death/discharge were recorded. Severely poisoned patients were defined as those with systolic blood pressure <=80 mmHg, pH <=7.2, or HCO3 <=15 meq/L or those who died, while patients with minor poisoning were those without any of these signs/symptoms. A control group (37 patients) was taken from other medically ill patients to detect probable effects of hypotension and metabolic acidosis on CO-Hb and methaemoglobin saturations. Of 96 patients, 27 died and 37 fulfilled the criteria for severe poisoning. All patients with carbon monoxide saturation >18% met the criteria to be included in the severe poisoning group and all with a SpCO >25% died. Concerning all significant variables in univariate analysis of severe ALP toxicity, the only significant variable which could independently predict death was carbon monoxide saturation. Due to high mortality rate and need for intensive care support, early prediction of outcome is vital for choosing an appropriate setting (ICU or ordinary ward). CO-oximetry is a good diagnostic and prognostic factor in patients with ALP poisoning even before any clinical evidence of toxicity will develop. PMID- 26899263 TI - Very early discharge versus early discharge versus non-early discharge in children with cancer and febrile neutropenia. AB - BACKGROUND: Chemotherapy-induced neutropenia is a common adverse effect in children with cancer. Due to the high relative risk of infections and infectious complications, standard care for children with cancer and febrile neutropenia consists of routine hospitalization and parenteral administration of broad spectrum antibiotics. However, there are less serious causes of febrile neutropenia; in a subgroup of these children, lengthy in-hospital treatment might be unnecessary. Various research groups have studied the adjustment of standard care to shorten in-hospital treatment for children with cancer and febrile neutropenia at low risk for bacterial infections. However, most of these studies were not done in a randomized matter. OBJECTIVES: To evaluate whether early discharge (mean/median of less than five days) from in-hospital treatment was not inferior to non-early discharge (mean/median of five days or more) and whether very early discharge (mean/median of less than 24 hours) was not inferior to early discharge, non-early discharge, or a combination of these, in children with cancer and febrile neutropenia. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (2015, issue 11), MEDLINE/PubMed (from 1945 to December 2015), EMBASE/Ovid (from 1980 to December 2015), the reference lists of relevant articles and review articles, and various conference proceedings (dependent on availability from 2005 to 2010 to 2013 to 2015). We scanned the International Standard Randomised Controlled Trials Number (ISRCTN) Register, the National Institute of Health Register for ongoing trials, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) on 9 January 2016. SELECTION CRITERIA: We included all randomized controlled trials and controlled clinical trials in which children with cancer and febrile neutropenia were divided in groups with different times of discharge. DATA COLLECTION AND ANALYSIS: We used standard methods of Cochrane and its Childhood Cancer Group. Two independent review authors performed study selection, data extraction, and risk of bias assessment. We entered data extracted from the included studies into Review Manager 5 and undertook analyses according to the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions. MAIN RESULTS: We included two randomized controlled trials assessing very early, early, non-early (or a combination of these) discharge in children with cancer and febrile neutropenia. We graded the evidence as low quality; we downgraded for risk of bias and imprecision. One study, Santolaya 2004, consisted of 149 randomized low-risk episodes and compared early discharge (mean/median of less than five days) to non-early discharge (mean/median of five days or more). This study found no clear evidence of difference in treatment failure (risk ratio (RR) 0.91, 95% confidence interval (CI) 0.24 to 3.50, P value = 0.89 for rehospitalization or adjustment of antimicrobial treatment, or both; Fischer's exact P value = 0.477 for death) or duration of treatment (mean difference -0.3 days, 95% CI -1.22 to 0.62, P value = 0.52 for any antimicrobial treatment; mean difference -0.5 days, 95% CI -1.36 to 0.36, P value = 0.25 for intravenous antimicrobial treatment; mean difference 0.2 days, 95% CI -0.51 to 0.91, P value = 0.58 for oral antimicrobial treatment). Costs were lower in the early discharge group (mean difference USD -265, 95% CI USD -403.14 to USD -126.86, P value = 0.0002). The second included study, Brack 2012, consisted of 62 randomized low risk episodes and compared very early discharge (mean/median of less than 24 hours) to early discharge (mean/median of less than five days). This study also found no clear evidence of difference in treatment failure (RR 0.54, 95% CI 0.15 to 1.89, P value = 0.34 for rehospitalization or adjustment of antimicrobial treatment (or both); Fischer's exact P value = 0.557 for death). Regarding duration of treatment, median duration of intravenous antimicrobial treatment was shorter in the very early discharge group (Wilcoxon's P value <= 0.001, stated in the study) and median duration of oral antimicrobial treatment was shorter in the early discharge group (Wilcoxon's P <= 0.001, stated in the study) as compared to one another. However, there was no clear evidence of difference in median duration of any antimicrobial treatment (Wilcoxon's P value = 0.34, stated in the study). Costs were not assessed in this study. Neither of the included studies assessed quality of life. Meta-analysis was not possible as the included studies assessed different discharge moments and used different risk stratification models. AUTHORS' CONCLUSIONS: Very limited data were available regarding the safety of early discharge compared to non-early discharge from in-hospital treatment in children with cancer and febrile neutropenia and a low risk for invasive infection. The absence of clear evidence of differences in both studies could be due to lack of power.Evidently, there are still profound gaps regarding very early and early discharge in children with cancer and febrile neutropenia. Future studies that assess this subject should have a large sample size and aim to establish uniform and objective criteria regarding the identification of a low risk febrile neutropenic episode. PMID- 26899265 TI - How culture shapes social cognition deficits in mental disorders: A review. AB - Social cognitive skills are indispensable for successful communication with others. Substantial research has determined deficits in these abilities in patients with mental disorders. In neurobiological development and continuing into adulthood, cross-cultural differences in social cognition have been demonstrated. Moreover, symptomatic patterns in mental disorders may vary according to the cultural background of an individual. Cross-cultural studies can thus help in understanding underlying (biological) mechanisms and factors that influence behavior in health and disease. In addition, studies that apply novel paradigms assessing the impact of culture on cognition may benefit and advance neuroscience research. In this review, the authors give an overview of cross cultural research in the field of social cognition in health and in mental disorders and provide an outlook on future research directions, taking a neuroscience perspective. PMID- 26899266 TI - PLK-1: Angel or devil for cell cycle progression. AB - PLK-1 is a key player in the eukaryotic cell cycle. Cell cycle progression is precisely controlled by cell cycle regulatory kinases. PLK-1 is a mitotic kinase that actively regulates the G2/M transition, mitosis, mitotic exit, and cytokinesis. During cell cycle progression, PLK-1 controls various events related to the cell cycle maturation, directly and/or indirectly. On the contrary, aberrant expression of PLK-1 is strongly associated with tumorigenesis and its poor prognosis. The misexpression of PLK-1 causes the abnormalities including aneuploidy, mitotic defects, leading to tumorigenesis through inhibiting the p53 and pRB genes. Therefore, we reviewed the role of PLK-1 in the cell cycle progression and in the tumorigenesis either as a cell cycle regulator or on an attractive anti-cancer drug target. PMID- 26899264 TI - Novel developments in mobile sensing based on the integration of microfluidic devices and smartphones. AB - Portable electronic devices and wireless communication systems enable a broad range of applications such as environmental and food safety monitoring, personalized medicine and healthcare management. Particularly, hybrid smartphone and microfluidic devices provide an integrated solution for the new generation of mobile sensing applications. Such mobile sensing based on microfluidic devices (broadly defined) and smartphones (MS(2)) offers a mobile laboratory for performing a wide range of bio-chemical detection and analysis functions such as water and food quality analysis, routine health tests and disease diagnosis. MS(2) offers significant advantages over traditional platforms in terms of test speed and control, low cost, mobility, ease-of-operation and data management. These improvements put MS(2) in a promising position in the fields of interdisciplinary basic and applied research. In particular, MS(2) enables applications to remote in-field testing, homecare, and healthcare in low-resource areas. The marriage of smartphones and microfluidic devices offers a powerful on chip operating platform to enable various bio-chemical tests, remote sensing, data analysis and management in a mobile fashion. The implications of such integration are beyond telecommunication and microfluidic-related research and technology development. In this review, we will first provide the general background of microfluidic-based sensing, smartphone-based sensing, and their integration. Then, we will focus on several key application areas of MS(2) by systematically reviewing the important literature in each area. We will conclude by discussing our perspectives on the opportunities, issues and future directions of this emerging novel field. PMID- 26899267 TI - Melatonin and the von Hippel-Lindau/HIF-1 oxygen sensing mechanism: A review. AB - There are numerous reports that melatonin inhibits the hypoxia-inducible factor, HIF-1alpha, and the HIF-1alpha-inducible gene, VEGF, both in vivo and in vitro. Through the inhibition of the HIF-1-VEGF pathway, melatonin reduces hypoxia induced angiogenesis. Herein we discuss the interaction of melatonin with HIF 1alpha and HIF-1alpha-inducible genes in terms of what is currently known concerning the HIF-1alpha hypoxia response element (HIF-1alpha-HRE) pathway. The von Hippel-Lindau protein (VHL), also known as the VHL tumor suppressor, functions as part of a ubiquitin ligase complex which recognizes HIF-1alpha as a substrate. As such, VHL is part of the oxygen sensing mechanism of the cell. Under conditions of hypoxia, HIF-1alpha stimulates the transcription of numerous HIF-1alpha-induced genes, including EPO, VEGF, and PFKFB3; the latter is an enzyme which regulates glycolysis. Data from several studies show that ROS generated in mitochondria under conditions of hypoxia stimulate HIF-1alpha. Since melatonin acts as an antioxidant and reduces ROS, these data suggest that the antioxidant action of melatonin could account for reduced HIF-1, less VEGF, and reduced glycolysis in cancer cells (Warburg effect). A direct or indirect inhibitory action (via the reduction in ROS) of melatonin on proteasome activity would account for much of the published data. PMID- 26899269 TI - Differences in age-dependent neural correlates of semantic processing between youths with autism spectrum disorder and typically developing youths. AB - Individuals with autism spectrum disorders (ASD) have aberrant neural activity during semantic judgments. We aimed to examine age-dependent neural correlates of semantic processing in boys with ASD as compared to typically developing boys (TD). We used functional MRI to investigate 37 boys with ASD (mean age = 13.3 years, standard deviation = 2.4) and 35 age-, sex-, Intelligence quotient (IQ)- and handedness-matched TD boys (mean age = 13.3 years, standard deviation = 2.7) from age 8 to 18 years. Participants had to indicate whether pairs of Chinese characters presented visually were related in meaning. Group (ASD, TD) * Age (Old, Young) ANOVA was used to examine the difference of age-related changes. Direct comparisons between the adolescent group and the child group were also performed. The behavioral results showed that the ASD group had lower accuracy in the related condition relative to the TD group. The neuroimaging results showed greater activation in the cuneus and less activation in the left inferior frontal gyrus in boys with ASD than TD boys. Children with ASD produced greater activation in the cuneus than TD children. Adolescents with ASD showed reduced left IFG activation as compared to TD adolescents. Our findings suggest that TD boys may engage more in higher-level processing of retrieving or selecting semantic features while boys with ASD may rely more on lower-level visual processing during semantic judgments. The findings imply different functional organizations of the semantic system between the two groups. Autism Res 2016, 9: 1263-1273. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc. PMID- 26899268 TI - Analysis of zwitterionic and anionic N-linked glycans from invertebrates and protists by mass spectrometry. AB - Glycomic analyses over the years have revealed that non-vertebrate eukaryotes express oligosaccharides with inorganic and zwitterionic modifications which are either occurring in different contexts as compared to, or are absent from, mammals. Examples of anionic N-glycans (carrying sulphate or phosphate) are known from amoebae, fungi, molluscs and insects, while zwitterionic modifications by phosphorylcholine, phosphoethanolamine and aminoethylphosphonate occur on N-, O- and lipid-linked glycans from trichomonads, annelids, fungi, molluscs, insects, cestodes and nematodes. For detection of zwitterionic and anionic glycans, mass spectrometry has been a key method, but their ionic character affects the preparation and purification; therefore, as part of a glycomic strategy, the possibility of their presence must be considered in advance. On the other hand, their ionisation and fragmentation in positive and negative ion mode mass spectrometry as well as specific chemical or enzymatic treatments can prove diagnostic to their analysis. In our laboratory, we combine solid-phase extraction, reversed and normal phase HPLC, MALDI-TOF MS, exoglycosidase digests and hydrofluoric acid treatment to reveal N-glycans modified with anionic and zwitterionic moieties in a wide range of organisms. It is to be anticipated that, as more species are glycomically analysed, zwitterionic and anionic modifications of N-glycans will prove rather widespread. This knowledge is - in the longer term - then the basis for understanding the function of this cornucopia of glycan modifications. PMID- 26899271 TI - A long lifetime switch-on iridium(III) chemosensor for the visualization of cysteine in live zebrafish. AB - A long lifetime iridium(III) complex chemosensor 1 for cysteine detection has been synthesized. The luminescence signal of 1 could be recognized in strongly fluorescent media through time-resolved emission spectroscopy (TRES). The detection of cysteine in a living zebrafish was demonstrated. PMID- 26899270 TI - Fast diffusion imaging with high angular resolution. AB - PURPOSE: High angular resolution diffusion imaging (HARDI) is a well-established method to help reveal the architecture of nerve bundles, but long scan times and geometric distortions inherent to echo planar imaging (EPI) have limited its integration into clinical protocols. METHODS: A fast imaging method is proposed here that combines accelerated multishot diffusion imaging (AMDI), multiplexed sensitivity encoding (MUSE), and crossing fiber angular resolution of intravoxel structure (CFARI) to reduce spatial distortions and reduce total scan time. A multishot EPI sequence was used to improve geometrical fidelity as compared to a single-shot EPI acquisition, and acceleration in both k-space and diffusion sampling enabled reductions in scan time. The method is regularized and self navigated for motion correction. Seven volunteers were scanned in this study, including four with volumetric whole brain acquisitions. RESULTS: The average similarity of microstructural orientations between undersampled datasets and their fully sampled counterparts was above 85%, with scan times below 5 min for whole-brain acquisitions. Up to 2.7-fold scan time acceleration along with four fold distortion reduction was achieved. CONCLUSION: The proposed imaging strategy can generate HARDI results with relatively good geometrical fidelity and low scan duration, which may help facilitate the transition of HARDI from a successful research tool to a practical clinical one. Magn Reson Med 77:696-706, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 26899272 TI - Selected Reviews from the 2016 BMT Tandem Meetings. PMID- 26899273 TI - Reprint of: Haploidentical Hematopoietic Stem Cell Transplantation: A Global Overview Comparing Asia, the European Union, and the United States. AB - One of the major projects of the Worldwide Network for Blood and Marrow Transplantation (WBMT) is to promote hematopoietic stem cell transplantation (HSCT) in emerging countries in the world. For these countries, HLA haploidentical HSCT (haplo-HSCT) from family members is an attractive approach because of its cost effectiveness. To learn the current status, including recent trends, of haplo-HSCT, the WBMT invited speakers from major transplant centers in 3 regions (Asia, Europe, and North America) to present at its annual WBMT Joint Session. This article represents the direct reports from these 3 speakers in addition to introductions by 2 WBMT speakers who address data from the Global Transplant Activity survey. It must be emphasized, however, that certain promising results of haplo-HSCT presented in this article were obtained at well experienced institutes. PMID- 26899274 TI - Reprint of: Acute Graft-versus-Host Disease: Novel Biological Insights. AB - Graft-versus-host disease (GVHD) continues to be a leading cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Recent insights into intestinal homeostasis and uncovering of new pathways and targets have greatly reconciled our understanding of GVHD pathophysiology and will reshape contemporary GVHD prophylaxis and treatment. Gastrointestinal (GI) GVHD is the major cause of mortality. Emerging data indicate that intestinal stem cells (ISCs) and their niche Paneth cells are targeted, resulting in dysregulation of the intestinal homeostasis and microbial ecology. The microbiota and their metabolites shape the immune system and intestinal homeostasis, and they may alter host susceptibility to GVHD. Protection of the ISC niche system and modification of the intestinal microbiota and metabolome to restore intestinal homeostasis may, thus, represent a novel approach to modulate GVHD and infection. Damage to the intestine plays a central role in amplifying systemic GVHD by propagating a proinflammatory cytokine milieu. Molecular targeting to inhibit kinase signaling may be a promising approach to treat GVHD, ideally via targeting the redundant effect of multiple cytokines on immune cells and enterocytes. In this review, we discuss insights on the biology of GI GVHD, interaction of microflora and metabolome with the hosts, identification of potential new target organs, and identification and targeting of novel T cell signaling pathways. Better understanding of GVHD biology will, thus, pave a way to develop novel treatment strategies with great clinical benefits. PMID- 26899275 TI - Reprint of: Fast Cars and No Brakes: Autologous Stem Cell Transplantation as a Platform for Novel Immunotherapies. AB - Autologous stem cell transplantation (ASCT) is indicated in a number of hematologic malignancies, including multiple myeloma, non-Hodgkin lymphoma, and Hodgkin lymphoma. Relapse, however, remains 1 of the main causes of post-ASCT failure, and several strategies are being investigated to decrease the risk of relapse of progression. Recent advances in the treatment of hematological malignancies have included adoptive transfer of genetically modified T cells that express chimeric antigen receptors or T cell receptors, as well the use of checkpoint inhibitors. Early clinical results in non-transplantation patients have been very promising. This review will focus on the use of gene-modified T cells and checkpoint inhibitors in stem cell transplantation. PMID- 26899276 TI - Author's reply. PMID- 26899277 TI - Impact of final kissing balloon inflation on vessel healing following drug eluting stent implantation: Insight from the optical coherence tomography sub study of the J-REVERSE trial. AB - BACKGROUND: We sought to clarify the impact of final kissing inflation (FKI) after single stenting of bifurcation lesions on vessel healing. METHODS: From the J-REVERSE registry enrolling 303 bifurcation lesions treated with provisional single stenting using sirolimus- (SES) or everolimus-eluting stent (EES), 65 lesions treated with (n=30) and without (n=35) FKI underwent 9-month follow-up optical coherence tomography. Average stent eccentricity index (SEI: minimum/maximum stent diameter) and neointimal unevenness score (NUS: maximum/average neointimal thickness of the same cross-section) for the proximal, bifurcation, and distal segments were compared between FKI and non-FKI groups. RESULTS: At the proximal segment, the FKI group demonstrated significantly larger average stent area with greater asymmetric stent expansion, and average lumen area remained significantly larger at 9-month follow-up despite a tendency toward greater neointimal proliferation. Jailed strut and thrombus incidence were also significantly lower at the side branch orifice, and NUS was significantly smaller at the bifurcation and proximal segments in the FKI group. CONCLUSIONS: Nine months after SES and EES treatment of bifurcation lesions, FKI reduced proximal segment luminal narrowing. Considering its homogeneous neointimal distribution and fewer jailed struts, FKI may be beneficial for treating bifurcation lesions. PMID- 26899278 TI - The increase in the rate of maternal deaths related to cardiovascular disease in Japan from 1991-1992 to 2010-2012. AB - BACKGROUND: Cardiovascular diseases (CVD), both genetic and acquired, increase the risk of maternal death (MD) unless proper genetic/clinical counseling is provided and a multidisciplinary approach is adopted during pregnancy. In recent decades, there has been a significant increase in the number of women with CVD of child-bearing age and in the incidence of pregnancy among relatively older women. However, the impact of this phenomenon on MD has not been carefully investigated. METHODS: This retrospective study compares the incidence and etiology of maternal deaths related to cardiovascular disease (MD-CVD) in Japan in 2010-2012 to that seen in 1991-1992. RESULTS: Seven cases of MD-CVD were reported in 1991-1992, compared to 15 in 2010-2012. In 2010-2012, the causes included aortic dissection (n=5), peripartum cardiomyopathy (n=3), sudden adult/arrhythmic death syndrome (n=2), acute cardiomyopathy (n=2), pulmonary hypertension (n=2), and myocardial infarction (n=1), and four of these causes were not encountered in 1991-1992. The incidence of MD over the total number of pregnancies decreased from 9.4 per 100,000 cases in 1990-1992 to 4.6 per 100,000 cases in 2010-2012 (p<0.05). However, the incidence of MD-CVD over the number of cases of MD increased from 2.9% in 1991-1992 to 9.7% in 2010-2012 (p<0.05). CONCLUSIONS: The present study demonstrates that the rate of MD-CVD among the cases of MD has increased 3-fold in Japan over the past 20 years. Thus, it is of critical importance to better understand the etiologies and early signs of MD-CVD and to devise an effective management program for pregnancies complicated by CVD. PMID- 26899279 TI - Global coherence during discourse production in adults: a review of the literature. AB - BACKGROUND: Global coherence is a metric of expressive language performance that represents the speaker's ability to initiate, plan and maintain a topic of discussion. Studies indicate that disruptions of global coherence can occur during the ageing process and following neurological disease or injury. However, little is known about the specific impact that the ageing process, disease or injury has on global coherence during discourse production. AIMS: To review the literature on global coherence in adult populations and assess the impact that age, disease or injury has on global coherence during expressive language tasks. METHODS & PROCEDURES: We completed an in-depth search of Medline and PyschInfo (1990-2014) to identify studies of global coherence in adult populations. We identified studies that included a comparison group and utilized a measure of global coherence during expressive language production among adults. OUTCOMES & RESULTS: Twenty studies comprised of 692 study participants who met inclusion criteria were identified for the review of the literature. Studies included participants without neurological impairments and individuals with aphasia, traumatic brain injury, dementia, generalized memory impairment and other neurological conditions. Study results indicated global coherence is an expressive language skill that is influenced by the ageing process and neurological disease or injury. CONCLUSIONS & IMPLICATIONS: Although evidence indicated that global coherence is negatively influenced by ageing and neurological disease/injury, the heterogeneity of study populations, measurement tools and study designs were limiting factors in determining the exact nature by which these factors impact the skill of global coherence. PMID- 26899280 TI - Gate modulation of proton transport in a nanopore. AB - Proton transport in confined spaces plays a crucial role in many biological processes as well as in modern technological applications, such as fuel cells. To achieve active control of proton conductance, we investigate for the first time the gate modulation of proton transport in a pH-regulated nanopore by a multi-ion model. The model takes into account surface protonation/deprotonation reactions, surface curvature, electroosmotic flow, Stern layer, and electric double layer overlap. The proposed model is validated by good agreement with the existing experimental data on nanopore conductance with and without a gate voltage. The results show that the modulation of proton transport in a nanopore depends on the concentration of the background salt and solution pH. Without background salt, the gated nanopore exhibits an interesting ambipolar conductance behavior when pH is close to the isoelectric point of the dielectric pore material, and the net ionic and proton conductance can be actively regulated with a gate voltage as low as 1 V. The higher the background salt concentration, the lower is the performance of the gate control on the proton transport. PMID- 26899281 TI - Surgical, functional and audiological evaluation of new Baha((r)) Attract system implantations. AB - Bone-anchored hearing aids are well-established solutions for treatment of hearing-impaired patients. However, classical systems with percutaneous abutments have disadvantages concerning aesthetics, hygiene and adverse soft tissue reactions. The study aimed to evaluate surgical, functional and audiological results of a new Baha((r)) Attract system, in which the sound processor is attached by magnetic force. Twenty patients implanted with a Baha((r)) Attract system were divided into two groups: A-bilateral mixed and conductive hearing loss, B-single-sided deafness, and evaluated during a 6-month follow-up. Parameters analysed comprised: (1) surgery and wound healing, (2) postoperative functional results (GBI, APHAB and BAHU questionnaires), (3) audiological results (free field speech in noise audiometry in two situations: with signal from implant side and from contralateral side). Obtained results revealed: mean time of surgery-44 min, soft tissue reduction-30 %, bone polishing-20 %, haematoma-10 %. Functional results showed: GBI total score-29.6 points, APHAB global score mean gain-23.5 %, BAHU 'good or very good' score for: aesthetic-85 %, hygiene-100 %, ease of placing the processor-100 %, stability of attraction-75 %. Audiological results-mean gain for the two analysed situations: 32.9 % (group A 36.5 %, group B-27.5 %). To conclude, the data obtained prove the safety and effectiveness of the Baha((r)) Attract system in patients with conductive and mixed hearing loss as well as in patients with single-sided deafness. Cosmetic aspects are highly acceptable and the idea of Attract itself is important for patients with limited manual dexterity. PMID- 26899282 TI - Increased mean platelet volume in patients with idiopathic subjective tinnitus. AB - Tinnitus is the perception of sound with no external stimulus and idiopathic subjective tinnitus is the most common type in adults. Mean platelet volume (MPV) alterations were shown in some inflammatory diseases and were evaluated as a clinically useful marker. Our aim was to investigate MPV alterations in idiopathic subjective tinnitus patients. A total of 101 patients and 54 age- and sex-matched healthy control subjects were enrolled in the study. Patients included in the study had complaints of tinnitus for at least 3 months. All patients underwent detailed otolaryngologic examination, blood sampling, pure tone audiometry, magnetic resonance imaging of ear, and vertebrobasilar artery Doppler ultrasonography to make the differential diagnosis of tinnitus. Blood sampling consisted of renal-liver-thyroid function tests, lipid profile, and complete blood count. All tests and examinations except the imaging modalities were also performed for the control group. There were no differences in age and sex distribution of groups. Mean platelet volume values were significantly increased in tinnitus patients when compared with controls (p = 0.001). We think that MPV can be qualified as a useful marker in tinnitus patients. PMID- 26899283 TI - Otorhinolaryngology residency in Spain: training satisfaction, working environment and conditions. AB - Europe-wide efforts are being initiated to define quality standards and harmonize Otolaryngology, Head and Neck Surgery (ORL-HNS)-specialty-training by creating an European board examination. However, differences within and between countries remain and are underinvestigated making comparisons and further improvement more difficult. The study aimed at assessing quality of training, satisfaction and quality of life of residents and recent ORL-HNS specialists in Spain and to trace similarities and differences to France and Germany administering anonymous online questionnaire to ORL-HNS-residents and recent specialists. 146 questionnaires were returned with answers of 75.6 % of residents, a mean age of 30 years and a female to male ratio of 1.46:1. The global satisfaction of training was high as 76 % would choose the same ENT training again, 86 % confirmed that responsibilities which were given to them were adapted to their level of training and 97 % felt well considered in their department. Ninety-two confirmed that helpful seniors contributed to a good work environment (75 %) and to a good organization within the department (69 %). The respondents spent on average 8.8 h per day at the hospital and covered on average 4.8 night duties or week-end shifts per month with mostly no post-day off (86 %). Seventy-four percent participated regularly at complementary training sessions. Research work was supported and guided in 59 %. This study is the first one, to our best of knowledge, to assess the ORL-HNS-training in Spain and to trace parallelisms and differences to other European countries, such as France and Germany. The satisfaction of training and supervision was high in Spain, but there are still efforts to make concerning resident's quality of life. Compared to France and Germany, satisfaction with ORL-HNS-training and the support and guidance provided by seniors was similar. Work conditions were comparable to those in France. Motivation, teaching and scientific output was higher in Spain, despite the salary being the lowest. PMID- 26899284 TI - Characterization of new allele influencing flowering time in bread wheat introgressed from Triticum militinae. AB - Flowering time variation was identified within a mapping population of doubled haploid lines developed from a cross between the introgressive line 8.1 and spring bread wheat cv. Tahti. The line 8.1 carried introgressions from tetraploid Triticum militinae in the cv. Tahti genetic background on chromosomes 1A, 2A, 4A, 5A, 7A, 1B and 5B. The most significant QTL for the flowering time variation was identified within the introgressed region on chromosome 5A and its largest effect was associated with the VRN-A1 locus, accounting for up to 70% of phenotypic variance. The allele of T. militinae origin was designated as VRN-A1f-like. The effect of the VRN-A1f-like allele was verified in two other mapping populations. QTL analysis identified that in cv. Tahti and cv. Mooni genetic background, VRN A1f-like allele incurred a delay of 1.9-18.6 days in flowering time, depending on growing conditions. Sequence comparison of the VRN-A1f-like and VRN-A1a alleles from the parental lines of the mapping populations revealed major mutations in the promoter region as well as in the first intron, including insertion of a MITE element and a large deletion. The sequence variation allowed construction of specific diagnostic PCR markers for VRN-A1f-like allele determination. Identification and quantification of the effect of the VRN-A1f-like allele offers a useful tool for wheat breeding and for studying fine-scale regulation of flowering pathways in wheat. PMID- 26899285 TI - Wavefront shaping through emulated curved space in waveguide settings. AB - The past decade has witnessed remarkable progress in wavefront shaping, including shaping of beams in free space, of plasmonic wavepackets and of electronic wavefunctions. In all of these, the wavefront shaping was achieved by external means such as masks, gratings and reflection from metasurfaces. Here, we propose wavefront shaping by exploiting general relativity (GR) effects in waveguide settings. We demonstrate beam shaping within dielectric slab samples with predesigned refractive index varying so as to create curved space environment for light. We use this technique to construct very narrow non-diffracting beams and shape-invariant beams accelerating on arbitrary trajectories. Importantly, the beam transformations occur within a mere distance of 40 wavelengths, suggesting that GR can inspire any wavefront shaping in highly tight waveguide settings. In such settings, we demonstrate Einstein's Rings: a phenomenon dating back to 1936. PMID- 26899287 TI - Prosthetic treatment outcome in patients with severe hypodontia: a systematic review. AB - Severe hypodontia (>=6 missing teeth) is associated with aesthetic and functional problems. Its presentation is heterogenic, and a variety of treatment modalities are used resulting in different treatment outcomes. As there is currently no standard treatment approach for patients with severe hypodontia, the literature was systematically reviewed with the focus on treatment outcomes. Medline, Embase and The Cochrane Central Register of Controlled Trials were searched (last search 24 August 2015). This was completed with a manual search of the reference lists of the selected studies. To be included, studies had to describe dental treatment outcome measure(s) in patients with severe hypodontia; there were no language restrictions. The methodological quality was assessed using MINORS criteria. Twenty-one studies were eligible, but the diversity in type and quality did not allow for a meta-analysis; seventeen studies had a retrospective design; sixteen studies described the results of implant treatment. Treatment with (partial) dentures, orthodontics, fixed crowns or bridges was sparsely presented in the eligible studies. Implant survival, the most frequently reported treatment outcome, ranging from 35.7% to 98.7%, was influenced by 'location' and 'bone volume'. The results of implant treatment in severe hypodontia patients are promising, but due to its heterogenic presentation, its low prevalence and the poor quality of the studies, evidence-based decision-making in the treatment of severe hypodontia is not yet feasible, thus prompting further research. PMID- 26899286 TI - AAV Gene Therapy for MPS1-associated Corneal Blindness. AB - Although cord blood transplantation has significantly extended the lifespan of mucopolysaccharidosis type 1 (MPS1) patients, over 95% manifest cornea clouding with about 50% progressing to blindness. As corneal transplants are met with high rejection rates in MPS1 children, there remains no treatment to prevent blindness or restore vision in MPS1 children. Since MPS1 is caused by mutations in idua, which encodes alpha-L-iduronidase, a gene addition strategy to prevent, and potentially reverse, MPS1-associated corneal blindness was investigated. Initially, a codon optimized idua cDNA expression cassette (opt-IDUA) was validated for IDUA production and function following adeno-associated virus (AAV) vector transduction of MPS1 patient fibroblasts. Then, an AAV serotype evaluation in human cornea explants identified an AAV8 and 9 chimeric capsid (8G9) as most efficient for transduction. AAV8G9-opt-IDUA administered to human corneas via intrastromal injection demonstrated widespread transduction, which included cells that naturally produce IDUA, and resulted in a >10-fold supraphysiological increase in IDUA activity. No significant apoptosis related to AAV vectors or IDUA was observed under any conditions in both human corneas and MPS1 patient fibroblasts. The collective preclinical data demonstrate safe and efficient IDUA delivery to human corneas, which may prevent and potentially reverse MPS1 associated cornea blindness. PMID- 26899290 TI - Cortical hyper-excitability in healthy children: evidence from habituation and recovery cycle phenomena of somatosensory evoked potentials. AB - AIM: To compare neurophysiological parameters of central nervous system excitability in healthy children/adolescents with those of healthy adults. METHOD: Two experimental protocols were used in 19 healthy children/adolescents (10 males and 9 females, mean age 9y 11mo [SD 2y 9mo], range 5-15y) and 19 healthy adults (8 males and 11 females, mean age 36y 6mo [SD 7y 9mo], range 27 51y). First, we administered repetitive trains of innocuous electrical stimulation of the median nerve and analysed habituation (progressive attenuation) of the cervical and cortical responses. Second, we administered several blocks of two closely timed electrical innocuous stimuli of the median nerve (with interstimulus intervals set at 5, 10, and 20ms in each block) and analysed the recovery index (the percentage of the response to the second stimulus with respect to that to the first). RESULTS: Clear-cut neurophysiological signs of cortical hyper-excitability were found in children/adolescents but not in adults. In contrast with the adults, the children/adolescents did not attenuate cortical responses to repetitive stimulation, and presented with extremely shortened recovery cycle. At baseline, both groups presented with comparable cortical responses. INTERPRETATION: Healthy children/adolescents present cortical hyper-excitability compared with healthy adults. These findings agree with previous findings that show an overall imbalance of excitatory and inhibitory neuronal and neurochemical mechanisms in favour of excitatory ones, in the healthy developing cerebral cortex. PMID- 26899289 TI - Frailty as a marker of adverse outcomes in patients with bladder cancer undergoing radical cystectomy. AB - OBJECTIVE: To investigate the modified frailty index (mFI) as a preoperative predictor of postoperative complications following radical cystectomy (RC) in patients with bladder cancer. MATERIALS AND METHODS: Patients undergoing RC were identified from the National Surgical Quality Improvement Program participant use files (2011-2013). The mFI was defined in prior studies with 11 variables based on mapping the Canadian Study of Health and Aging Frailty Index to the National Surgical Quality Improvement Program comorbidities and activities of daily livings. The mFI groups were determined by the number of risk factors per patient (0, 1, 2, and>=3). Univariable and multivariable regression were performed to determine predictors of Clavien 4 and 5 complications, and a sensitivity analysis was performed to determine the mFI value that would be a significant predictor of Clavien 4 and 5 complications. RESULTS: Of the 2,679 cystectomy patients identified, 843 (31%) of patients had an mFI of 0, 1176 (44%) had an mFI of 1, 555 (21%) had an mFI of 2, and 105 (4%) had an mFI>=3. Overall, 1585 (59%) of patients experienced a Clavien complication. When stratified at a cutoff of mFI>=2, the overall complication rate was not different (61.7% vs. 58.3%, P = 0.1), but the mFI2 or greater group had a significantly higher rate of Clavien grade 4 or 5 complications (14.6% vs. 8.3%, P<0.001) and overall mortality rate (3.5% vs. 1.8%, P = 0.01) in the 30-day postoperative period. The multivariate logistic regression model showed independent predictors of Clavien grade 4 or 5 complications were age>80 years (odds ratio [OR] = 1.58 [1.11-2.27]), mFI2 (OR = 1.84 [1.28-2.64]), and mFI3 (OR = 2.58 [1.47-4.55]). CONCLUSIONS: Among patients undergoing RC, the mFI can identify those patients at greatest risk for severe complications and mortality. Given that bladder cancer is increasing in prevalence particularly among the elderly, preoperative risk stratification is crucial to inform decision-making about surgical candidacy. PMID- 26899291 TI - Risk factors for patients with multiple synchronous primary cancers involving oral and oropharyngeal subsites. AB - OBJECTIVE: To evaluate risk factors and prognosis for multiple synchronous primary cancers (MSPCs) associated with head and neck squamous cell carcinoma. STUDY DESIGN: The retrospective study included 1623 patients. RESULTS: The most common MSPC site involved was the head and neck region. The presence of multiple oral dysplastic lesions (P < .001) was the sole risk factor for the occurrence of MSPCs. A multivariate survival analysis showed that the pathologic grade (P = .003) was an independent predictive factor for the 5-year disease-specific survival of patients with MSPCs. A Kaplan-Meier analysis showed that the 5-year disease-specific survival of patients who developed MSPCs was worse than that of patients who did not develop MSPCs (P = .020). CONCLUSIONS: MSPCs are a significant negative prognostic factor for patients with head and neck squamous cell carcinoma. However, a worse prognosis is predicted for patients with MSPCs with several features: a higher pathologic grade, a more aggressive growth pattern, male gender plus a tobacco or alcohol habit, and no multiple oral dysplastic lesions. PMID- 26899292 TI - Ameloblastic neoplasia spectrum: a cross-sectional study of MMPS expression and proliferative activity. AB - OBJECTIVE: To compare the proliferation and the expression of matrix metalloproteinases (MMPs; MMP-2 and MMP-9) in solid and unicystic ameloblastomas with ameloblastic carcinomas. STUDY DESIGN: Five cases of ameloblastic carcinoma (AC), 18 cases of solid ameloblastoma (SA), and seven of unicystic ameloblastoma (UA) were selected. The immunohistochemical expression of MMPs was assessed by the percentage of positive tumor cells and stained stroma. The mean argyrophilic nucleolar organizer region (AgNOR) and the percentage of cells with more than one AgNOR per nucleus were evaluated. RESULTS: Statistically significant higher mean AgNOR was observed in AC than in SA and UA. MMP-2 was expressed similarly in tumor and stroma among groups. MMP-9 was higher in the stroma of SA than that of UA (P = .0484). CONCLUSIONS: The cell proliferation was related to the greater aggressiveness of AC. High expression of MMP-2 and MMP-9 in all lesions highlighted the importance of these enzymes in the biology of ameloblastic tumors. PMID- 26899293 TI - Adenomatoid odontogenic tumor with peripheral cemento-osseous reactive proliferation: report of 2 cases and review of the literature. AB - Two cases of a rare variant of adenomatoid odontogenic tumor encompassed by a prominent reactive cemento-osseous proliferation are reported. This unique variant of adenomatoid odontogenic tumor has only been seen twice in the authors' collective experience. Literature documenting the histopathologic patterns of adenomatoid odontogenic tumor and the occurrence of other combined lesions other is reviewed and discussed. PMID- 26899294 TI - Aggressive radiolucent lesion of the mandible. PMID- 26899295 TI - Clinical study on mandibular fracture after marginal resection of the mandible. AB - OBJECTIVES: Postoperative mandibular fracture (PMF) after marginal resection (MR) of the mandible remains an unresolved issue, and it has been reported that at least 10 mm of postoperative mandibular body height (PMBH) is required to prevent PMF. This study evaluated the clinical, physical, and structural risk factors for PMF in MR patients and determined appropriate preventive measures for PMF. STUDY DESIGN: This retrospective study included 44 patients with lower gingival carcinoma who underwent MR. PMF occurred in four of these patients. Thirteen associated factors identified from medical records and radiographs were statistically analyzed. RESULTS: Mandibular body height (MBH) preservation ratio originally evaluated as less than 0.3, more than 20 remaining teeth after surgery, and inferior alveolar canal (IAC) exposure were significant risk factors for PMF. Prostheses and number of remaining teeth were also correlated with PMF. CONCLUSIONS: The preserved mandibular bone should be reinforced in patients with an MBH preservation ratio of less than 0.3, more than 20 remaining teeth after surgery, and intraoperative IAC exposure. Patients with prostheses are at an increased risk of PMF compared with those without because of stable occlusion and a strong occlusal force. Our novel findings provide useful reference standards for PMF prevention in MR patients. PMID- 26899296 TI - A Novel Platinum-based Compound with Preferential Cytotoxic Activity against a Panel of Cancer Cell Lines. AB - PURPOSE: Cisplatin as a platinum (Pt)-based chemotherapeutic compound is commonly applied for the treatment of several types of cancer. Nonetheless, drug resistance and severe adverse effects have been observed upon using cisplatin. Here, we have explored the cytotoxicity of novel Pt-based compounds on several cancer cell lines. METHODS: Five synthetic Pt compounds as well as cisplatin were investigated by XTT assay to determine their cytotoxicity against cell lines originated from prostate, ovary, and breast cancers at different time periods at various concentrations. Additionally, the apoptosis rate in cell lines was determined using flow cytometry. Binding to DNA was investigated through spectrophotometric and viscometric studies. RESULTS: With the exception of one compound, all of the Pt-complexes effectively killed the prostate cancer cell lines (i.e. PC-3 and DU 145). One compound, [Pt(2,2'- dipyridylamine)Cl4].DMF, was chosen as the most potent compound due to its high selective cytotoxic activity and its cytotoxicity was further tested and compared with that of cisplatin on SKOV-3, Caov-4, MDA-MB-231, and MCF7 cell lines. [Pt(2,2' dipyridylamine)Cl4].DMF had a higher selective cytotoxic capacity in comparison with cisplatin at higher concentrations and longer culture periods. Furthermore, as related to apoptosis induction, treatment with [Pt(2,2'-dipyridylamine)Cl4 ].DMF was significantly more effective than that of cisplatin in five out of six examined cell lines. [Pt(2,2'-dipyridylamine)Cl4].DMF was shown to intercalate into DNA. CONCLUSIONS: The current study introduced a novel Pt-based complex with highly selective and potent in vitro anti-tumor impacts superior to those of cisplatin, a conventional chemotherapeutic agent. [Pt (2,2' dipyridylamine)Cl4].DMF could be regarded as a promising antitumor agent in future investigations. PMID- 26899298 TI - A new HLA-A allele, HLA-A*11:120, sequenced in a Chinese hematopoietic stem cell donor. AB - HLA-A*11:120 has one nucleotide change from HLA-A*11:01:01:01 where 295 T(ACC) is changed to S(AGC). PMID- 26899297 TI - Risk of infection following colonization with carbapenem-resistant Enterobactericeae: A systematic review. AB - BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) have emerged as important health care-associated pathogens. Colonization precedes infection but the risk of developing infection amongst those colonized with CRE is not clear. METHODS: We searched multiple databases for studies reporting rates of CRE colonized patients subsequently developing infection. RESULTS: Ten studies fulfilled our inclusion criteria, including 1,806 patients used in our analysis. All studies were observational and conducted among adult inpatients. The cumulative rate of infection was 16.5% in our study. The most common site of infection was the lung, identified in half of patients, followed in decreasing frequency by urinary tract; primary bloodstream; and skin and soft tissue, including surgical sites. Colonization or infection by CRE prolonged stay and was associated with a 10% overall mortality in our analysis. CONCLUSION: Our study results suggest an overall 16.5% risk of infection with CRE amongst patients colonized with CRE. Given the high mortality rate observed with CRE infection and the difficulty in treating these infections, research to investigate and develop strategies to eliminate the colonization state are needed. PMID- 26899299 TI - Transplantation of miRNA-34a overexpressing adipose-derived stem cell enhances rat nerve regeneration. AB - Peripheral nerve injury is an ongoing challenge in reconstructive surgery. Adipose-derived stem cell (ADSC) application is reported to improve nerve regeneration. In the present study, we evaluated the potential benefit of 34a ADSCs for never regeneration. Lentiviral vectors containing miRNA-34a were constructed and ADSCs were transduced. The obtained 34a-ADSCs were used to regenerate the sciatic nerve in surgically induced sciatic nerve injury rat model. Sprague-Dawley (SD) rats were randomly divided into two groups, a 34a-ADSC group and an Lv-ADSC group. Functional nerve recovery was assessed by walking track analysis at 12 weeks after surgery. In addition, histology, including light microscopy and transmission electron microscopy, and immunohistochemistry, was utilized to investigate the nerve repair effects of 34a-ADSC. Results showed that reconstruction of the injured sciatic nerve had been significantly enhanced by restoration of nerve continuity and functional recovery in the 34a-ADSC group compared with the Lv-ADSC group. Furthermore, sciatic nerve conduction velocity and compound nerve action potential in the 34a-ADSC group was much higher than that in the Lv-ADSC group (30.72 +/- 2.95 m/s vs. 22.73 +/- 1.91 m/s, p< 0.0001; 11.93 +/- 0.76 mV vs. 9.52 +/- 0.53 mV, p = 0.0418). This study raises the possibility of using miRNA-34a overexpressed ADSCs as a promising alternative for nerve regeneration. PMID- 26899300 TI - Carfilzomib-induced cardiotoxicity mitigated by dexrazoxane through inhibition of hypertrophic gene expression and oxidative stress in rats. AB - Carfilzomib (CFZ) is an inhibitor of proteasome that is generally used in the treatment of multiple myeloma but due to its cardiotoxicity clinical use may be limited. Dexrazoxane (DZR), an inhibitor of topoisomerase-II, prevents cardiac damage by reducing the formation of reactive oxygen species and hypertrophic gene expression. This study evaluated the protective effect of DZR on CFZ-induced cardiotoxicity. Thirty-two male Albino rats were randomly divided into four groups (n = 8). Group I received DMSO, Group II received CFZ (4 mg/kg, intraperitoneally [i.p.]) twice weekly up to day 16, Group III received DZR (20 mg/kg, i.p.) for 16 days and CFZ twice weekly for 16, Group IV received DZR (40 mg/kg, i.p.) for 16 days and CFZ twice weekly for 16. CFZ-induced cardiotoxicity was assessed by hematological, biochemical, mRNA expression, oxidative stress and histopathological studies. CFZ-induced significant changes have been observed in blood parameters including red blood cells, white blood cells, hemoglobin and hematocrit concentrations which were associated with increase in cardiac enzymes markers like creatine kinase (CK), CK-MB and lactate dehydrogenase. Treatment with DZR reversed the hematological statistics and the biochemical markers of CFZ induced cardiotoxicity. Furthermore, DZR also attenuated the effects of CFZ induced toxic effect on redox markers such as malondialdehyde and reduced glutathione. Above findings were further confirmed by beta-myosin heavy chain (beta-MHC) and alpha-MHC (alpha-MHC) gene expression. Histopathological reports suggested that DZR ameliorates CFZ-induced changes in cardiac cellular architecture in rats. These results confirm that DZR protects heart from CFZ induced cardiotoxicity. PMID- 26899301 TI - Higher serum pentosidine, an advanced glycation end product, in branch atheromatous disease among small vessels occlusion. AB - BACKGROUND: Cerebral branch atheromatous disease (BAD) are more likely to experience progressing stroke and neurological deterioration compared with lacunar infarction, although these small vessels occlusions are difficult to discriminate in acute phase of ischemic stroke. Advanced glycation end products including pentosidine have been implicated in atherosclerosis, and were associated with atheroma plaque progression. However, little is known about a relationship between serum pentosidine and small vessels occlusion. METHODS: Serum pentosidine levels were measured in 56 patients (BAD, 21; lacunar, 35) with small vessels occlusion among consecutive 208 patients with acute ischemic stroke at initial hospitalization as well as other risk factors of stroke. Univariate and multivariate logistic regression analyses were performed to analyze relationship between risk factors including pentosidine and small vessels occlusion. Sensitivity and selectivity of pentosidine to discriminate BAD from lacunar were calculated. RESULTS: Serum pentosidine was significantly higher in BAD group than lacunar group (0.081 +/- 0.081MUg/ml and 0.046 +/- 0.043MUg/ml, p < 0.05). In the univariate logistic regression analyses, BAD was significantly related to high serum pentosidine (p = 0.01), absence of dyslipidemia (p = 0.04), and worse outcome measured by modified Rankin Scale (p = 0.03). Multivariate logistic regression analysis showed that only high level of serum pentosidine was the independent risk factor for BAD (p = 0.03). Sensitivity and specificity were 90% and 44%, respectively. CONCLUSION: High level of serum pentosidine in acute phase of stroke was associated with BAD, which led to worse outcome among patients with small vessels occlusion. PMID- 26899302 TI - The muscle activation patterns of lower limb during stair climbing at different backpack load. AB - Stair climbing under backpack load condition is a challenging task. Understanding muscle activation patterns of lower limb during stair climbing with load furthers our understanding of the factors involved in joint pathology and the effects of treatment. At the same time, stair climbing under backpack load requires adjustments of muscle activations and increases joint moment compared to level walking, which with muscle activation patterns are altered as a result of using an assistive technology, such as a wearable exoskeleton leg for human walking power augmentation. Therefore, the aim of this study was to analyze lower limb muscles during stair climbing under different backpack load. Nine healthy volunteers ascended a four-step staircase at different backpack load (0 kg, 10 kg, 20 kg, 30 kg). Electromyographic (EMG) signals were recorded from four lower limb muscles (gastrocnemius, tibialis anterior, hamstring, rectus femoris). The results showed that muscle activation amplitudes of lower limb increase with increasing load during stair climbing, the maximum RMS of gastrocnemius are greater than tibialis anterior, hamstring and rectus femoris whether stair climbing or level walking under the same load condition. However, the maximum RMS of hamstring are smaller than gastrocnemius, tibialis anterior and rectus femoris. The study of muscle activation under different backpack load during stair climbing can be used to design biomechanism and explore intelligent control based on EMG for a wearable exoskeleton leg for human walking power augmentation. PMID- 26899303 TI - Simple size control of TiO2 nanoparticles and their electrochemical performance: emphasizing the contribution of the surface area to lithium storage at high rates. AB - The particle size effects of TiO2 nanoparticles (TNPs), which are composed of small crystallites, on Li ion storage are a very fundamental and important subject. However, size control of TNPs under 200 nm using a sol-gel method has been limited due to the highly reactive precursor, titanium alkoxide. In this study, TNPs with various sizes even under 100 nm are obtained by controlling the reactant concentrations in a mixed solvent of ethanol and acetonitrile. Among them, three different sizes of TNPs are prepared to compare the Li ion storage capacity, and 60 nm TNPs are found to have the best reversible capacity of 182 mA h g(-1) after 50 cycles at 1 C and a remarkable rate performance of 120 mA h g( 1) at 10 C. Capacity increase upon cycling is observed in the size-controlled TNPs, and the explanation of this phenomenon is proposed to the lattice volume expansion of TiO2 upon intercalation for enabling further penetration of the electrolyte into the particles' interior. Moreover, the capacity at high rates is more closely related to the surface area from Hg porosimetry analysis than from typical N2 adsorption/desorption analysis. PMID- 26899304 TI - Universality in boundary domain growth by sudden bridging. AB - We report on universality in boundary domain growth in cluster aggregation in the limit of maximum concentration. Maximal concentration means that the diffusivity of the clusters is effectively zero and, instead, clusters merge successively in a percolation process, which leads to a sudden growth of the boundary domains. For two-dimensional square lattices of linear dimension L, independent of the models studied here, we find that the maximum of the boundary interface width, the susceptibility chi, exhibits the scaling chi ~ L(gamma) with the universal exponent gamma = 1. The rapid growth of the boundary domain at the percolation threshold, which is guaranteed to occur for almost any cluster percolation process, underlies the the universal scaling of chi. PMID- 26899305 TI - CO2 leakage-induced vegetation decline is primarily driven by decreased soil O2. AB - To assess the potential risks of carbon capture and storage (CCS), studies have focused on vegetation decline caused by leaking CO2. Excess soil CO2 caused by leakage can affect soil O2 concentrations and soil pH, but how these two factors affect plant development remains poorly understood. This hinders the selection of appropriate species to mitigate potential negative consequences of CCS. Through pot experiments, we simulated CO2 leakage to examine its effects on soil pH and soil O2 concentrations. We subsequently assessed how maize growth responded to these changes in soil pH and O2. Decreased soil O2 concentrations significantly reduced maize biomass, and explained 69% of the biomass variation under CO2 leakage conditions. In contrast, although leaked CO2 changed soil pH significantly (from 7.32 to 6.75), it remained within the optimum soil pH range for maize growth. This suggests that soil O2 concentration, not soil pH, influences plant growth in these conditions. Therefore, in case of potential CO2 leakage risks, hypoxia-tolerant species should be chosen to improve plant survival, growth, and yield. PMID- 26899306 TI - The efficacy of six elite isolates of the fungus Chondrostereum purpureum against the sprouting of European aspen. AB - The sprouting of broad-leaved trees after cutting is problematic in forest regeneration areas, along roads and railways, under electric power and above gas pipe lines. In Finland, one of the most difficult species to control in these areas is the European aspen (Populus tremula), which produces both stump sprouts and root suckers after saplings have been cut. In this study, we investigated whether a decay fungus of broad-leaved trees, Chondrostereum purpureum, could be used as a biological control agent against aspen sprouting. The efficacy of six elite strains of C. purpureum (improved earlier in a breeding process) was investigated on aspen for three years. The most efficient C. purpureum strain, R53, tested earlier on birch (Betula pendula and B. pubescens), was efficient in causing mortality of aspen stumps and preventing the development of root suckers. With this strain, stump mortality was 78%, while significantly lower in control stumps which were cut only (47%). Aspen trees in the vicinity of the treatments (within a 10 m radius around each sapling) decreased the efficacy of C. purpureum. This study shows that the decay fungus C. purpureum can successfully be used in the sprout control of aspen saplings. PMID- 26899307 TI - Molecularly imprinted polymer on a SiO2 -coated graphene oxide surface for the fast and selective dispersive solid-phase extraction of Carbamazepine from biological samples. AB - A surface carbamazepine-imprinted polymer was grafted and synthesized on the SiO2 /graphene oxide surface. Firstly SiO2 was coated on synthesized graphene oxide sheet using the sol-gel technique. Prior to polymerization, the vinyl group was incorporated on to the surface of SiO2 /graphene oxide to direct selective polymerization on the surface. Methacrylic acid, ethylene glycol dimethacrylate and ethanol were used as monomer, cross-linker and porogen, respectively. Nonimprinted polymer was also prepared for comparison. The properties of the molecularly imprinted polymer were characterized using field-emission scanning electron microscopy and Fourier-transform infrared spectroscopy. The surface molecularly imprinted polymer was utilized as an adsorbent of dispersive solid phase extraction for separation and preconcentration of carbamazepine. The effects of the different parameters influencing the extraction efficiency, such as sample pH were investigated and optimized. The specificity of the molecular imprinted polymer over the nonimprinted polymer was examined in absence and presence of competitive drugs. The carbamazepine calibration curve showed linearity in the ranges 0.5-500 MUg/L. The limits of detection and quantification under the optimized conditions were 0.1 and 0.3 MUg/L, respectively. The within day and between-day relative standard deviations (n = 3) were 3.6 and 4.3%, respectively. Furthermore, the relative recoveries for spiked biological samples were above 85%. PMID- 26899308 TI - Action of ellagic acid on the melanin biosynthesis pathway. AB - BACKGROUND: Tyrosinase is an enzyme involved in the first steps of the melanogenesis process. It catalyzes the hydroxylation of monophenols to o diphenols and the oxidation of the latter to o-quinones. Ellagic acid (EA) is a phenolic compound which has been described as a tyrosinase inhibitor and is used in the cosmetic industry as a whitening agent. However, it has hydroxyl groups in ortho position and could act as a substrate rather than inhibitor. This aspect should be taken into consideration when using this compound as a cosmetic ingredient due to the reactive character of o-quinones. OBJECTIVE: To determine whether ellagic acid is a substrate or an inhibitor of tyrosinase, to characterize it kinetically and interpret its role in the melanogenesis process. METHODS: UV-vis spectrophotometry was used to follow the action of tyrosinase on typical substrates and ellagic acid. A chronometric method was chosen for the kinetic characterization of ellagic acid. RESULTS: Ellagic acid is not an inhibitor per se but an alternative substrate of tyrosinase. It is oxidized by the enzyme to an unstable o-quinone. Its kinetic characterization provided low Michaelis and catalytic constants (KM(EA)=138+/-13MUM and kcat(EA)=0.47+/-0.02s( 1)). Furthermore, ellagic acid, which is a powerful antioxidant, may chemically reduce the o-quinones (o-dopaquinone) and semiquinones, in this way inhibiting the melanogenesis. CONCLUSION: Ellagic acid is oxidized by tyrosinase, producing reactive o-quinones. As an antioxidant it can inhibit the melanogenesis process. This first aspect should be taken into consideration in its application as a cosmetic ingredient due to the toxicity of o-quinones and its ability to modify the redox status of the cell. PMID- 26899309 TI - Anti-Inflammatory and Antioxidant Mechanism of Tangeretin in Activated Microglia. AB - Tangeretin, a flavonoid from citrus fruit peels, has been proven to play an important role in anti-inflammatory responses and neuroprotective effects in several disease models, but further study is necessary for elucidating the detailed mechanisms of these effects. In this study, we examined the anti inflammatory effect of tangeretin in lipopolysaccharide (LPS)-stimulated microglia. We first observed that tangeretin inhibited LPS-induced production of nitric oxide, tumor necrosis factor alpha, interleukin (IL)-6, and IL-1beta, as well as LPS-induced mRNA expression of inducible nitric oxide synthases and cytokines. Additionally, we found that the activities, mRNA levels, and protein levels of matrix metalloproteinase (MMP)-3 and MMP-8 were inhibited, while the expression of tissue inhibitor of metalloproteinase-2 was enhanced by tangeretin in LPS-stimulated microglia. Further mechanistic study showed that tangeretin suppressed LPS-induced phosphorylation of mitogen-activated protein kinases and Akt. Also, tangeretin inhibited nuclear factor-kappaB by upregulating sirtuin 1 and 5'-adenosine monophosphate-activated protein kinase. We further demonstrated the antioxidant effect of tangeretin by showing that tangeretin inhibited reactive oxygen species production and p47(phox) phosphorylation, while enhancing the expression of heme oxygenase-1 and the DNA binding activity of nuclear factor erythroid 2-related factor 2 to the antioxidant response element in LPS stimulated microglia. Taken together, the results of the present study demonstrate that tangeretin possesses a potent anti-inflammatory and antioxidant effect in microglia. PMID- 26899310 TI - Cardiac structure and function and effects of enzyme replacement therapy in patients with mucopolysaccharidoses I, II, IVA and VI. AB - BACKGROUND: While enzyme replacement therapy (ERT) has been shown to improve endurance and joint mobility for patients with mucopolysaccharidoses (MPS) I, II, IVA and VI, the impact of ERT on cardiac abnormalities remains uncertain. METHODS: Medical records and echocardiograms of 28 Taiwanese MPS patients (9 with MPS I, 7 with MPS II, 7 with MPS IVA, and 5 with MPS VI) treated with ERT for 1 10.8years were retrospectively reviewed. RESULTS: At start of ERT, z scores>2 were identified in 46% and 75% for left ventricular mass index (LVMI) and interventricular septum thickness in diastole (IVSd) in these patients, respectively. Twenty-four patients (86%) had valvular heart disease. After ERT, the mean IVSd z score of all patients decreased significantly from 3.87 to 2.57 (p=0.016). For 11 patients starting ERT before 12years of age, z scores for both LVMI and IVSd decreased significantly (p<0.01) after ERT. However, the condition of valve regurgitation or stenosis did not show improvement despite ERT. CONCLUSIONS: ERT was shown to be an effective therapy for reducing cardiac hypertrophy, with best results seen when ERT was started at an early age. ERT, however, had little impact on valvular heart disease. PMID- 26899311 TI - Response styles in factual items: Personal, contextual and cultural correlates. AB - This study investigated response styles in factual items and explored their associations with personal, contextual and cultural factors. Responses on various factual questions, cognitive tests and interviewers' observational data from a total of 152,514 respondents in 22 countries in the Programme for the International Assessment of Adult Competencies (PIAAC) were analysed. Indexes of extreme, midpoint and acquiescent response styles were extracted from Likert scale and dichotomous responses of factual items. A general response style (GRS) with a positive loading of extreme response style and negative loadings of midpoint and acquiescent response styles was confirmed. This factor showed a similar cross-cultural patterning as another general factor from attitudinal and self-evaluative items of Likert scales in a previous study, which indicated the pervasiveness of response styles irrespective of types of survey items. In a multilevel analysis, the individual-level GRS was found to be negatively related to being male, educational level and literacy competency, and positively related to 3rd-person presence and background noise, and at country level negatively associated with socioeconomic development. Cross-level interactions were also found. Implications on the pervasiveness and nature of response styles are discussed. PMID- 26899312 TI - Click chemistry functionalization improving the wideband optical-limiting performance of fullerene derivatives. AB - A novel kind of monodonor-bisacceptor (D-A-A) C60 charge-transfer complex was synthesized by the high-yielding [2+2] click chemistry reaction and the Prato reaction. Both electrochemical and UV-vis spectra studies were carried out and they proved that the side groups of the fullerene derivatives played an important role in the energy gaps, and also affected the third-order non-linear optical response. The experimental investigation on the third-order non-linear optical phenomena of the fullerene derivatives was measured using the Z-scan technique at different wavelengths (532 nm and 1064 nm). All the compounds exhibited very special non-linear optical properties when pumped by 21 ps pulses at 532 nm which suggested that there were two different types of reversible photo-isomerization. The optical-limiting performance has also been studied which proved indirectly the mechanism models of the reversible photo-isomerization. PMID- 26899313 TI - Examining Time to Initiation of Biologic Disease-modifying Antirheumatic Drugs and Medication Adherence and Persistence Among Texas Medicaid Recipients With Rheumatoid Arthritis. AB - PURPOSE: Little is known about the transition from nonbiologic disease-modifying antirheumatic drugs (DMARDs) to biologic DMARDs or about individual nonbiologic DMARD use patterns among patients with rheumatoid arthritis (RA). This study examined time to initiation of biologic DMARDs and nonbiologic DMARD medication adherence and persistence among Texas Medicaid recipients with RA taking nonbiologic DMARDs. METHODS: In this retrospective study (July 1, 2003-December 31, 2010) of the Texas Medicaid database, patients were aged 18 to 62 years at index, were diagnosed with RA (International Classification of Diseases, Ninth Revision, Clinical Modification, code 714.xx), had no claims for nonbiologic or biologic DMARDs in the preindex period, and had a minimum of 2 prescription claims for the same nonbiologic DMARD in the postindex period. Kaplan-Meier survival analysis and log-rank tests were used to compare time to initiation of biologic DMARDs according to nonbiologic DMARD type and therapy. Adherence and persistence were examined according to nonbiologic type and therapy by using ANOVA models and chi(2), Duncan, and t tests. FINDINGS: On average, patients were 47.9 (+/- 10.4) years of age, mostly female (89.1%) and Hispanic (55.2%). Methotrexate (MTX) and leflunomide (LEF) users took the shortest time to initiate biologic DMARDs (207 [190] days and 188 [205] days, respectively). LEF users had the highest mean adherence of 37.5% (27.5%), which was similar to MTX users (35.7% [26.9%]), whereas dual-therapy users had the lowest mean adherence at 17.1% (14.4%). Sulfasalazine users (108 [121] days) had the lowest persistence, whereas LEF (227 [231] days) and MTX (211 [222] days) users had the longest persistence. Nonbiologic DMARD monotherapy users were more adherent than dual therapy users (32.6% [25.8%] vs 17.1% [14.4%]). IMPLICATIONS: These results should be interpreted in light of some study limitations, such as using proportion of days covered as a proxy for adherence, not having clinical data to control for RA severity, and lack of generalizability to all US populations. Given the study findings, both clinicians and other decision makers may want to investigate the potential driving factors of initiation of biologic DMARDs to provide effective RA management and consider patient education programs to enhance medication adherence and persistence to RA medications. PMID- 26899314 TI - Cervical Cancer in Women Aged 35 Years and Younger. AB - PURPOSE: Age has been evaluated as a prognostic factor in cervical cancer in both hospital- and population-based studies. Results regarding the relation of age and cervical cancer prognosis are conflicting. This study pursued a contemporary assessment of the association of extreme young age at the time of a cervical cancer diagnosis on survival. METHODS: Institutional review board approval was obtained, and retrospective data collection at 2 academic institutions was performed. Inclusion criteria involved women <= 35 years diagnosed with cervical cancer between 1990 and 2012. Data included demographic and prognostic information pertinent to survival and progression. Characteristics of very young (<= 25 years) and young (>25-35 years) women were compared. Kaplan-Meier estimates, the log-rank test, and Cox proportional hazards modeling were used to assess the association of age, tumor histology, grade, stage, and parametrial involvement with progression-free survival (PFS) and overall survival (OS). FINDINGS: Incident cases (n = 126) of cervical cancer in patients <= 35 years of age were identified of which complete clinical information was available for 114 women. Fifteen percent (17 of 114) were <= 25 years, with the remaining 85% (97 of 114) being 26 to 35 years of age. Race, smoking status, and marital status were comparable between the 2 groups. Squamous histology dominated overall (77 of 114; 68%) with adenocarcinoma contributing ~25% (30 of 114; 26%) of cases. The majority (96 of 114, 84%) had either stage 1A (31 of 114, 27%) or 1B (65 of 114, 57%) disease. A log-rank test revealed no evidence to infer a difference in either PFS or OS among the age groups (P = 0.511 and P = 0.340). In a univariate analysis, grade and stage significantly affected OS (P < 0.0001, P = 0.045), and stage significantly affected PFS (P < 0.0001). In multivariate modeling, presence of parametrial involvement and histologic cancer type significantly affected both PFS (P = 0.002, P = 0.001) and OS (P = 0.001, P = 0.001). IMPLICATIONS: Tumor histology, parametrial involvement, and stage continue to be strong prognosticators for PFS and OS. Progression and survival outcomes are age independent in women with cervical cancer <= 35 years of age. Further study of a larger young cohort may potentially yield different outcomes. PMID- 26899315 TI - Development and functional morphology of the mouthparts and foregut in larvae and post-larvae of Macrobrachium jelskii (Decapoda: Palaemonidae). AB - The morphology of the mouthparts and foregut of the larvae and post-larvae of Macrobrachium jelskii was investigated to determine their functional roles in feeding, in order to understand the larval feeding behaviour and the changes that occur during its development. The mouthparts and foregut of the zoea I and II are morphologically similar, rudimentary and non-functional in feeding. Only in the final larval stage, zoea III, do the external mouthparts and foregut become structurally more complex and thus likely to play a potential role in feeding. Two behavioral trials (point of no return, point of reserve saturation) evaluated the resistance to starvation in zoea I, II, and III. The results indicate that they have sufficient nutritional reserves to permit them to complete metamorphosis without feeding. Overall, our results suggest that the zoea I and II of Macrobrachium jelskii engage in obligate lecithotrophy and zoea III in facultative lecithotrophy. PMID- 26899316 TI - Effects of Palygorskite Inclusion on the Growth Performance, Meat Quality, Antioxidant Ability, and Mineral Element Content of Broilers. AB - The present study was conducted to investigate different levels of palygorskite supplementation on the growth performance, meat quality, muscular oxidative status, and mineral element accumulation of broilers. One hundred ninety-two 1 day-old Arbor Acres broiler chicks were allocated to four dietary treatments with six replicates of eight chicks per replicate. Birds in the four treatments were given a basal diet supplemented with 0, 5, 10 and 20 g/kg palygorskite for 42 days, respectively. Compared with the control group, neither 5 g/kg nor 10 g/kg palygorskite inclusion affected growth performance of broilers during the 42-day study (P > 0.05). However, the highest level of palygorskite supplementation at 20 g/kg increased feed/gain ratio (F/G) of broilers (P < 0.001). Yellowness (P < 0.001) and redness (P = 0.003) of breast muscle and yellowness of leg muscle (P = 0.001) were decreased by palygorskite supplementation at the levels of 10 g/kg and especially 20 g/kg. In addition, redness of leg muscle was also reduced by the inclusion of 20 g/kg palygorskite (P = 0.009). In contrast, malonaldehyde (MDA) accumulation in the breast muscle was significantly increased by 20 g/kg palygorskite supplementation (P < 0.001). Supplementation of palygorskite at either 10 or 20 g/kg significantly decreased lead (Pb) accumulation in the breast (P = 0.001) or thigh (P = 0.045) and copper (Cu) accumulation in the breast (P = 0.022). In conclusion, growth performance, meat color, and antioxidant capacity of meat would reduce with the increasing level of palygorskite supplementation, whereas a higher level of palygorskite (10 or 20 g/kg) can alter mineral element accumulations in muscles as evidenced by reduced muscular Cu and Pb contents. PMID- 26899317 TI - Nickel-Related Intestinal Mucositis in IBS-Like Patients: Laser Doppler Perfusion Imaging and Oral Mucosa Patch Test in Use. AB - Nickel (Ni) is often the trigger of irritable bowel syndrome (IBS)-like gastrointestinal disorders: its ingestion may cause allergic contact mucositis, identifiable by means of oral mucosa patch test (omPT). OmPT effectiveness has been proven, but it is still an operator-dependent method. Laser Doppler perfusion imaging (LDPI) was tested to support omPT in Ni allergic contact mucositis diagnosis. Group A: 22 patients with intestinal/systemic symptoms related to the ingestion of Ni-containing foods. Group B: 12 asymptomatic volunteers. Ni-related symptoms and their severity were tested by a questionnaire. All patients underwent Ni omPT with clinical evaluation at baseline (T0), after 30 min (T1), after 2 h (T2), and after 24-48 h (T3). LDPI was performed to evaluate the mean mucosal perfusion at T0, T1, and T2. Statistical analysis was performed by ANOVA test and Bonferroni multiple comparison test. All 22 Ni-sensitive patients (group A) presented oral mucosa hyperemia and/or edema at T2. Eight out of the same 22 patients presented a local delayed vesicular reaction at T3 (group A1), unlike the remaining 14 out of 22 patients (group A2). All 12 patients belonging to control group B did not show any alteration. The mean mucosal perfusion calculated with LDPI showed an increase in both subgroups A1 and A2. In group B, no significant perfusion variations were observed. LDPI may support omPT for diagnostic purposes in Ni allergic contact mucositis. This also applies to symptomatic Ni-sensitive patients without aphthous stomatitis after 24-48 h from omPT and that could risk to miss the diagnosis. PMID- 26899318 TI - Effects of Dietary Selenium Supplementation on Seminiferous Tubules and SelW, GPx4, LHCGR, and ACE Expression in Chicken Testis. AB - We investigated the effects of dietary selenium (Se) supplementation on the development of chicken testis and the expression of selenoprotein W (SelW), glutathione peroxidase4 (GPx4), luteinizing hormone/choriogonadotropin receptor (LHCGR), and angiotensin converting enzyme (ACE). Sixty roosters were assigned randomly into the control group fed with a basic diet (containing 0.3 mg Se/kg) and the experimental group fed with a diet (containing 0.6 mg Se/kg). The testes were collected individually at age of 6, 9, and 12 weeks. Se was supplemented in chicken feed for 15 days before sampling. The results indicated that dietary Se affected the number of cells in the seminiferous tubules and viability of Sertoli cells in vitro culture. SelW and GPx4 expression in the testes increased significantly in the experimental group compared to that in the control group. LHCGR expression in the testes increased significantly in the experimental group after 12 weeks compared to that in the control group. In contrast, ACE expression was inhibited in the experimental group compared to that in the control group. These results suggest that dietary supplementation with Se improved development of the seminiferous tubules at the cellular level and that SelW, GPx4, LHCGR, and ACE are involved. PMID- 26899319 TI - Selenium Deficiency-Induced Inflammation and Increased Expression of Regulating Inflammatory Cytokines in the Chicken Gastrointestinal Tract. AB - Selenium (Se), a nutritionally essential trace element, plays an important role in various aspects of health for a wide range of species, including birds. Se deficiency inhibits the growth of immune organs and decreases immune function, leading to many inflammatory diseases. The present study determined the effects and mechanism of dietary Se deficiency on gastrointestinal tract tissue inflammation. The histopathological changes showed that Se deficiency induced inflammatory lesions in the gastrointestinal tract tissues (glandular stomach, gizzard, duodenum, small intestine, and rectum). The expression levels of PTGE (prostagland E synthase), COX-2 (cyclooxygenase-2), TNF-alpha (tumor necrosis factor alpha), and NF-kappaB (nuclear transfer factor kappaB) in the gastrointestinal tract tissues (glandular stomach, gizzard, duodenum, small intestine, and rectum) were determined by qPCR on days 15, 25, 35, 45, and 55, respectively. The results showed that Se deficiency induced high expression levels of PTGE, COX-2, TNF-alpha, and NF-kappaB in the gastrointestinal tract tissues. The effects were more obvious in the duodenum and small intestine than those in the glandular stomach, gizzard, and rectum. In addition, the expression levels of these proteins in the gastrointestinal tract tissue increased in a time dependent manner with Se deficiency feeding time. Furthermore, Se deficiency induced the production of pro-inflammatory factors, thus aggravating inflammatory lesions in the gastrointestinal tract. The effect of Se deficiency on inflammation and other gastrointestinal tract diseases should be further studied. PMID- 26899320 TI - Selenium-Fertilized Tritordeum (* Tritordeum Ascherson et Graebner) as Dietary Selenium Supplement in Laying Hens: Effects on Egg Quality. AB - The aim of the present study was to investigate the effect of adding selenium (Se) in cereal production by fertilization on Se concentration in laying hen eggs. Tritordeum (*Tritordeum Ascherson et Graebner), a new cereal from the cross between durum wheat and a wild barley species having accreditation as natural crop species, was produced using selenate as Se-fertilizer. Hy-Line Brown laying hens were randomly allocated to two dietary treatments and fed for 10 weeks. Hens were fed two corn-soybean meal-based diets comprising a control basal diet including Tritordeum (100 g/kg diet) cv. Aucan grown without Se fertilization (containing background Se only from premix supplying 1,0 times birds' requirements) and a test-diet containing Se-enriched Tritordeum at the same level of the control diet. No difference was observed among dietary treatments on feed consumption and efficiency, egg mass, and laying rate, whereas egg yolk Se and vitamin E contents as well as liver and plasma Se levels were significantly influenced by dietary Se-enriched Tritordeum. Based on our findings, Se-enriched Tritordeum improved egg quality without affecting hens' productive performance. Thus, Se-fertilized Tritordeum may represent a valuable natural source of Se compared to conventional dietary supplements. PMID- 26899321 TI - Selenoprotein X Gene Knockdown Aggravated H2O2-Induced Apoptosis in Liver LO2 Cells. AB - To determine the roles of selenoprotein X gene (Selx) in protecting liver cells against oxidative damage, the influences of Selx knockdown on H2O2-induced apoptosis in human normal hepatocyte (LO2) cells were studied. pSilencer 3.1 was used to develop knockdown vector targeting the 3'-UTR of human Selx. The Selx knockdown and control cells were further exposed to H2O2, and cell viability, cell apoptosis rate, and the expression levels of mRNA and protein of apoptosis related genes were detected. The results showed that vector targeting the 3'-UTR of Selx successfully silenced mRNA or protein expression of SelX in LO2 cells. Selx knockdown resulted in decreased cell viability, increased percentage of early apoptotic cells, decreased Bcl2A1 and Bcl-2 expression, and increased phosphorylation of P38 in LO2 cells. When Selx knockdown LO2 cells were exposed to H2O2, characteristics of H2O2-induced cell dysfunctions were further exacerbated. Taken together, our findings suggested that SelX played important roles in protecting LO2 cells against oxidative damage and reducing H2O2-induced apoptosis in liver cells. PMID- 26899322 TI - How the rice weevil breaks down the pectin network: Enzymatic synergism and sub functionalization. AB - Pectin is the most complex polysaccharide in nature and highly abundant in plant cell walls and middle lamellae, where it functions in plant growth and development. Phytopathogens utilize plant pectin as an energy source through enzyme-mediated degradation. These pectolytic enzymes include polygalacturonases (PGs) of the GH28 family and pectin methylesterases (PMEs) of the CE8 family. Recently, PGs were also identified in herbivorous insects of the distantly related plant bug, stick insect and Phytophaga beetle lineages. Unlike all other insects, weevils possess PMEs in addition to PGs. To investigate pectin digestion in insects and the role of PMEs in weevils, all PME and PG family members of the rice weevil Sitophilus oryzae were heterologously expressed and functionally characterized. Enzymatically active and inactive PG and PME family members were identified. The loss of activity can be explained by a lack of substrate binding correlating with substitutions of functionally important amino acid residues. We found subfunctionalization in both enzyme families, supported by expression pattern and substrate specificities as well as evidence for synergistic pectin breakdown. Our data suggest that the rice weevil might be able to use pectin as an energy source, and illustrates the potential of both PG and PME enzyme families to functionally diversify after horizontal gene transfer. PMID- 26899324 TI - [Research advances of K-ras mutation in the prognosis and targeted therapy of gastric cancer]. AB - K-ras mutations have been described in 30% of human cancers with significantly different mutation frequencies. High K-ras mutation frequency is found in many cancers such as pancreas and lung cancers, whereas, gastric cancer has a relatively low K-ras mutation frequency. In recent years, numerous researches have focused on the K-ras mutation in gastric cancer. This review summarizes the K-ras mutation frequency in gastric cancer, the relationship of K-ras mutation with clinicopathologic features and prognosis of gastric cancer patients, targeted therapy for K-ras mutated gastric cancer, some small-molecular inhibitors of K-ras, and development of targeted therapy drugs for K-ras signaling pathway in gastric cancer. PMID- 26899325 TI - [Role of miR-155 in invasion and metastasis of lung adenocarcinoma A549 cells]. AB - OBJECTIVE: To investigate the role and mechanism of miR-155 in invasion and metastasis of lung adenocarcinoma A549 cells. METHODS: Real-time PCR and fluorescence in situ hybridization were used to detect the miR-155 expression in patients' lung adenocarcinoma and adjacent tissue and lymph nodes. Scratch test and Transwell migration assay were used to assess the effect of miR-155 on the A549 cell migration and invasion capability. Bioinformatics software was used to predict the target genes of miR-155, and using luciferase to assay the target gene. Western blot and real-time PCR were performed to confirm the role of miR 155 expression in the regulation of target gene PTEN. RESULTS: The real-time quantitative PCR showed that the miR-155 expression levels in adjacent normal tissue, lung adenocarcinoma and metastatic lymph nodes were 4.1+/-0.5, 9.6+/-3.1 and 7.8+/-2.2, respectively. The in situ hybridization showed that the expression rates of miR-155 in the adjacent normal tissue, lung adenocarcinoma and metastatic lymph nodes were (23.2+/-15.3)%, (75.4+/-20.2)% and (60.4+/-25.1)%, respectively. The Scratch assay showed that the wound healing rates in the miR 155 mimics group, miR-155 mimics NC group, miR-155 inhibitor group and miR-155 inhibitor NC group at 24 h were (43.2+/-2.2)%, (21.3+/-4.2)%, (24.3+/-5.3)%, and (35.2+/-5.1)%, and that at 48 h were (75.2+/-4.5)%, (52.6+/-5.2)%, (39.4+/-4.2)%, and (51.5+/-4.3)%, respectively. Dual luciferase reporter gene assay showed that the value of the luciferase in the miR-155 mimics group co-transfected with PTEN 3'UTR-containing wild-type and mutant plasmids were 4.7+/-0.5 and 7.3+/-0.7, and the miR-155 mimics luciferase values of the control group co-transfected with PTEN 3'UTR-containing wild-type and mutant plasmids were 7.8+/-0.9 and 7.5+/-0.8, respectively. The real-time quantitative fluorescence PCR showed that the relative expression of PTEN protein in the miR-155 mimics group, miR-155 mimics control group, miR-155 mimics inhibitor group, and miR-155 inhibitor control group were 0.5+/-0.3, 1.0+/-0.1, 2.2+/-0.2 and 1.2+/-0.1, respectively. The Western blot assay detected that the relative expression of PTEN protein levels in the miR-155 mimics group, miR-155 mimics control group, miR-155 inhibitor group and miR-155 inhibitor control group were 0.4+/-0.1, 1.0+/-0.3, 2.8+/-0.2 and 1.4+/-0.1, respectively. The differences in PTEN mRNA and protein expressions of the four groups were statistically significant (P<0.05 for all). CONCLUSIONS: miR-155 may promote the invasion and metastasis of lung adenocarcinoma through reducing the target PTEN gene expression. PMID- 26899326 TI - [A Case report of rare recurrent multiple skin cancer nodules in the radiation field after radiotherapy for cervical cancer]. PMID- 26899323 TI - IGF-I stimulates ERbeta and aromatase expression via IGF1R/PI3K/AKT-mediated transcriptional activation in endometriosis. AB - Estrogen receptor beta (ERbeta, encoded by ESR2 gene) and cytochrome P450 aromatase (encoded by CYP19A1 gene) play critical roles in endometriosis, and the levels of insulin-like growth factor-I (IGF-I) in the peritoneal fluid are significantly higher in patients with endometriosis compared with those in normal women. However, the effects and mechanisms of IGF-I on ERbeta and aromatase expression remain to be fully elucidated. In this study, human endometriotic stromal cells (ESCs) and endometrial cells (EMs) derived from ovarian endometriomas and eutopic endometrial tissues. ESCs were cultured with IGF-I, signal pathway inhibitors, and siRNAs. ERbeta and aromatase expression were measured by real-time PCR and Western, respectively. The binding of c-Jun and CREB to the ESR2 and CYP19A1 promoters was assessed by chromatin immunoprecipitation assay. Animal experiments were performed in a xenograft mouse model. Levels of IGF-I mRNA in ESCs were markedly higher than those in EMs. IGF-I upregulated ERbeta and aromatase expression in ESCs after stimulation of the IGF1R/PI3K/AKT pathway. Following IGF-I treatment, a marked increase in c-Jun and CREB phosphorylation occurred, enhancing binding to the ESR2 and CYP19A1 promoters. An IGF1R inhibitor in vivo reduced IGF-I-induced endometriosis graft growth and ERbeta and aromatase expression. In conclusion, this is the first report to describe a mechanistic analysis of ERbeta and aromatase expression regulated by IGF-I in ESCs. Moreover, an IGF1R inhibitor impeded ectopic lesion growth in nude mice. These findings suggest that an inhibitor of IGF1R might have therapeutic potential as an antiendometriotic drug. KEY MESSAGES: Level of IGF-I mRNA in ESCs is markedly higher than that in EMs. IGF-I up-regulates ERbeta and aromatase expression via IGF1R/PI3K/AKT pathway. C-Jun and CREB are recruited to ESR2 or CYP19A1 promoter by IGF-I stimulation. IGF-1R inhibitors in vivo impede the growth of ectopic lesions in nude mice. PMID- 26899327 TI - [Construction of a RNAi lentiviral vector targeting ARK5 gene and its effect on the biological behavior of gastric cancer SGC7901 cells]. AB - OBJECTIVE: To construct a RNA interference lentiviral vector aimed at human ARK5 (AMPK-related protein kinase 5) gene and explore its effect on the biologic behavior of human gastric cancer SGC7901 cells. METHODS: Targeting human ARK5 mRNA coding sequence, we designed three specific short hairpin RNAs (shRNAs) and constructed the lentiviral vector, then infected human gastric cancer SGC7901 cells with this vector. Afterwards, we used qPCR and Western blot for detecting the silencing effect on ARK5 gene, MTT colorimetric assay to measure the cell proliferation, cell scratch test for cell migration and Transwell for cell invasion, and flow cytometry analysis for apoptosis in cells treated with glucose starvation and TNF-alpha. RESULTS: Sequencing proved that the recombinant lentiviral vector containing ARK5-shRNA-3 was constructed successfully. Real time fluorescent quantitative PCR assay showed that the expression abundance of ARK5 gene in the normal control group, negative control group and ARK5-shRNA-3 infected group were 1.002+ 0.082, 1.001+ 0.050 and 0.140+ 0.003, respectively, showing a statistically significant difference (P<0.01). Cell scratch test showed that the cell migration rate of ARK5-shRNA-3 infected group was (38.5+ 4.3)%, significantly lower than that of the normal control group [(72.4+ 6.4)%] and negative control group [(75.1+ 7.1)%, P<0.01]. The results of Transwell test showed that the number of penetrating cells in the normal control group, negative control group and ARK5-shRNA-3 transfection group were 257.4+/-12.3, 245.7+/ 11.6, 112.5+/-7.8, with a significant difference (P<0.01). After glucose starvation and TNF-alpha-treatment for 24 h, the cell death rate of the normal control group, negative control group and ARK5-shRNA-3 group were (11.7+/-3.2)%, (12.3+/-2.6)% and (30.8+/-4.3)%, respectively, showing that the cell apoptosis rate of ARK5-shRNA-3 transfected group was significantly higher than that of the normal control and negative control groups (P<0.01). CONCLUSIONS: We have successfully constructed a recombinant lentiviral vector which can efficiently silence ARK5 gene. Using it we can inhibit the proliferation, migration, invasion of tumor cells, and promote cell apoptosis under the condition of TNF-alpha treatment and glucose starvation. PMID- 26899328 TI - [The CK2 inhibitor quninalizarin enhances the anti-proliferative effect of icotinib on EGFR-TKIs-resistant cell lines and its underlying mechanisms]. AB - OBJECTIVE: To explore whether quninalizarin, an specific inhibitor of protein kinase CK2, could sensitize icotinib in EGFR-TKIs (epithelial growth factor receptor-tyrosine kinase inhibitor)-resistant cell lines and uncover the underlying mechanisms. METHODS: MTT assay was performed to evaluate the inhibitory effect of quninalizarin, icotinib or the combination of both on cell proliferation in several lung adenocarcinoma cell lines. Western blot assay was used to assess if combined inhibition of EGFR and protein kinase CK2 by icotinib and quninalizarin, exerts effect on the expression and phosphorylation of major proteins of EGFR signaling pathways. RESULTS: The IC50 of HCC827, H1650, H1975 and A549 cells for icotinib were (8.07+/-2.00)MUmol/L, (66.01+/-6.64)MUmol/L, (265.60+/-9.47)MUmol/L and (87.88+/-6.8)MUmol/L, respectively, indicating that HCC827 cells are sensitive to icotinib, and the H1650, H1975 and A549 cells are relatively resistant to icotinib. When treated with both quninalizarin and icotinib in the concentration of 50 MUmol/L, the viability of H1650, H1975 and A549 cells was (40.64+/-3.73)%, (65.74+/-3.27)% and (44.96+/-0.48)%, respectively, significantly lower than that of H1650, H1975 and A549 cells treated with 50 MUmol/L icotinib alone (55.05+/-1.22)%, (71.98+/-1.60)% and (61.74+/-6.18)%, respectively (P<0.01 for all). When treated with both 100 MUmol/L quninalizarin and 100 MUmol/L icotinib, the viability of H1650, H1975 and A549 ells were (23.35+/-0.81)%, (55.70+/-1.03)%, (33.42+/-1.33)%, respectively, significantly lower than the viability of H1650, H1975 and A549 cells treated with 100 MUmol/L icotinib alone (40.57+/-2.65)%, (62.40+/-2.05)% and (44.97+/ 8.20)%, respectively, (P<0.01 for all). The two-way ANOVA analysis showed that compared with the viability of EGFR-TKIs-resistant cells (H1650, H1975, A549) treated with 50 MUmol/L and 100 MUmol/L icotinib alone, the viability of cells treated with icotinib and quinalizarin were significantly suppressed, and the differences were statistically significant (P<0.01). In addition, the phosphorylation form of Akt and ERK (namely p-Akt and p-ERK) were significantly down-regulated by treating with quninalizarin and icotinib together in the H1650 cells while the expression of Akt and ERK changed little. CONCLUSIONS: Quinalizarin, as a specific CK2 inhibitor, may overcome icotinib resistance by inhibiting proliferation mediated by Akt and ERK in human lung adenocarcinoma cell lines, and enhances the suppressive effect of icotinib on the proliferation of EGFR-TKIs-resistant human lung adenocarcinoma cells. PMID- 26899329 TI - [Optimization of the method to cultivate NK cells from abandoned white cells]. AB - OBJECTIVE: Using abandoned white cells separated from preparation of blood products to cultivate NK cells in vitro, and to optimize the method of cultivation of allogeneic NK cells for clinical application. METHODS: Abandoned white cells separated from blood production were collected from 15 healthy donors. PBMCs were isolated from the abandoned white cells and cultured for 17 days using culture bottles as previously coated antibodies (group CD3 mAb was coated with CD3 mAb, group CD 16mAb was coated with CD16mAb, and group CD3 mAb+ CD16 mAb was coated with CD3 mAb and CD16 mAb). Flow cytometry was used to determine the ratio of CD3(-)CD56(+) cells, expression of activated cell surface receptors, and secretion of IFN-gamma. The anti-tumor cytotoxicity against K562 and Raji cells was determined using LDH cytotoxicity assay and flow cytometry. RESULTS: After expansion for 17 days, the proportions of CD3(-)CD56(+) cells was (15.19+/-12.22)% in the group CD3 mAb, (83.63+/-10.63)% in the group CD16 mAb, (49.40+/-12.64)% in the group CD3 mAb+ CD16 mAb, and it was (16.34+/-10.51)% before expansion. The total number of NK cells was more than 10(9). The expression ratios of NK cell surface activated receptors NKp30 and NKp46 were significantly increased, while that of the NKG2D was not significantly changed. The NK cells after expansion showed high cytotoxicity activity against K562 cells, reaching up to(76.97+/-3.16)% when effector-cell-to-target-cell ratio (E?T ratio) was 40?1. CONCLUSIONS: NK cells can be obtained from abandoned white cells after cultivation for 17 days, with a purity up to 90% and total cell number of more than 10(9). Their activity was reinforced, the anti-tumor cytotoxicity activity was increased, and may meet the standard of clinical therapeutic application. PMID- 26899330 TI - [Application of DNA-image cytometry in the diagnosis of lung cancer]. AB - OBJECTIVE: To explore the value of DNA-image cytometry (DNA-ICM) in diagnosis of lung cancer. METHODS: 532 cases of bronchoalveolar lavage fluid (BALF) and (or) bronchial brushing cytology (216 cases from lung cancer patients and 209 cases from benign lung disease patients) were detected by DNA-ICM and liquid-based cytology (LBC), respectively. The sensitivity and specificity of the two methods were compared. RESULTS: The sensitivity and specificity of DNA-ICM were 69.2% and 100.0%, and which of LBC were 46.7% and 97.9%, respectively. The sensitivity of DNA-ICM was significantly higher than that of LBC method in the diagnosis of lung cancer (P<0.05). The sensitivity and specificity of DNA-ICM of BALF were 71.9% and 100.0%, while those of LBC were 48.2% and 98.5%. The sensitivity and specificity of DNA-ICM of bronchial brushing cytology were 62.8% and 100.0%, while those of LBC were 43.0% and 95.3%. The sensitivity of DNA-ICM of BALF and bronchial brushing cytology were higher than that of LBC method (P<0.05). There were 107 patients who underwent BALF and bronchial brushing cytology simultaneously, the sensitivity of DNA-ICM of BALF was higher than that of bronchial brushing cytology (P<0.05). Among different histologic types of the lung cancers, the sensitivity of squamous carcinoma was higher that of adenocarcinoma. CONCLUSIONS: DNA-ICM has great application value in the diagnosis of lung cancer. DNA-ICM in combination with LBC can increase the detection rate of lung cancer. DNA-ICM of BALF is worthy of application in clinical practice. PMID- 26899331 TI - [Identification and significance of myeloid-derived suppressor cells in peripheral blood of breast cancer patients]. AB - OBJECTIVE: To investigate the presence, biological features, and clinical significance of myeloid-derived suppressor cells (MDSCs) in breast cancer patients. METHODS: Eighty-four cases of breast cancer, 37 cases of benign breast tumor and 21 cases of healthy individuals were included in this study. Samples of peripheral blood (2 ml) were collected, and in the breast cancer patients, blood samples were taken both before and after treatment. Flow cytometry using anti CD11b, CD33, CD14 and HLA-DR antibody was conducted to identify the unique membrane markers of MDSCs, and statistical analysis was performed to explore the relationship between MDSCs and clinical factors. Cell isolation and in vitro assay were used to test T cell function. RESULTS: CD11b(+) CD33(+) CD14(-) MDSCs were present in the blood of breast cancer patients, and these MDSCs were histologically of mononuclear cells. Cell proliferation assay confirmed that MDSCs inhibited proliferation of homologous T cells in vitro. MDSCs levels in patients with breast cancer, benign disease and the health control were (15.93+/ 3.17)%, (8.92+/-4.42)% and (5.02+/-2.75)%, respectively, with a statistically significant difference (P<0.001) between breast cancer patients and the other subjects (patients with benign lesions and healthy controls). The expression level of MDSCs in patients with breast cancer was associated with surgical treatment, but not with age, disease stage, lymph node metastasis, ER or PR expression. MDSCs levels were significantly lower in post-operative patients[(7.83+/-3.78) %] than the (15.37+/-2.49) % in patients before surgery (P<0.001). CONCLUSIONS: The results of this study demonstrate that MDSCs are present in the peripheral blood of breast cancer patients and the level of MDSCs is associated with surgical treatment. Our findings suggest that CD11b(+) CD33(+) CD14(-) MDSCs are likely involved in breast cancer initiation and development, and may become a novel biomarker to facilitate diagnosis and to predict clinical outcomes of breast cancer. PMID- 26899332 TI - [Assessment and significance of human epidermal growth factor receptor 2 gene status in breast cancer with polysomy of chromosome 17]. AB - OBJECTIVE: To explore the impact of polysomy of chromosome 17 on the interpretation of human epidermal growth factor receptor 2 (HER2) status and its clinical significance in breast cancers. METHODS: Clincopathological data of 338 breast cancer patients were collected, and the association of clinicopathological characteristics with polysomy of chromosome 17 was analyzed. Based on the American Society of Clinical Oncology /College of American Pathologists updated recommendations of HER2 testing in breast cancer in 2013, the relationships between the copy number of centromeres on chromosome 17 (CEP17) and HER2 status, other important biological markers and clincopathological features of breast cancer were analyzed statistically. RESULTS: Immunohistochemical examination revealed that among the 338 breast cancer cases, there were 9 (2.7%) HER2 negative cases, 309 (91.4%) HER2-equivocal cases, and 20 (5.9%) HER2-positive cases. The FISH analysis showed that there were 226 (66.9%) HER2-negative cases, 13 (3.8%) HER2-equivocal cases, and 99 (29.3%) HER2-positive cases. Among the 338 breast cancer patients, 42 (12.4%) cases were identified as chromosome 17 polysomy (polysomy 17), 291 (86.1%) cases were chromosome 17 disomy, and 5 (1.3%) cases were chromosome 17 monosomy. Polysomy 17 showed significant correlation with the intensity of HER2 protein expression (P=0.046). The HER2 FISH results and HER2 gene copy number of polysomy 17 cases showed significant differences from the non-polysomy 17 cases (P<0.001). There were no significant differences of HER2/CEP17 ratio between the polysomy 17 and non-polysomy 17 groups (P=0.930). Polysomy 17 cases showed a significant relationship with tumor grading and Ki-67 index (P<0.05), but not with the age of patient, tumor size, lymph node metastasis, ER and PR expressions, and effect evaluation of neoadjuvant chemotherapy (P>0.05). CONCLUSIONS: In the breast cancer with polysomy of chromosome 17, assessment of the absolute copy number of HER2 signals is even more important, and the HER2/CEP17 ratio and HER2 protein expression levels should be comprehensively evaluated together. PMID- 26899333 TI - [Analysis of the mutations of EGFR and phosphatidylinositol 3-kinase catalytic alpha-polypeptide and their association with clinicopathological features]. PMID- 26899334 TI - [Value of diffusion-weighted magnetic resonance imaging in prediction of the response to preoperative chemoradiotherapy in rectal carcinoma]. AB - OBJECTIVE: To investigate the value of diffusion weighted imaging (DWI) in predicting the efficacy of preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer. METHODS: From 2007 to 2012, 86 patients with histopathologicaIly proven rectal cancer who underent pre-CRT were enrolled in this study prospectively. Diffusion-weighted MRl was performed in all patients before pre-CRT, while it was performed in part of the patients during and after pre-CRT as well.ADC values of the tumors were calculated on the workstation. Patients were assigned to the tumor downstaged group or the tumor nondownstaged group on the basis of T staging. The change in ADC following treatment and the difference in ADC between groups were analyzed. RESULTS: Of the 86 patients after surgery, 20 were diagnosed with T0, 2 with T1, 17 with T2, 44 with T3 and 3 with T4. 39 patients were classified as the downstaged group, of which 18 were of pCR. The remaining 47 patients were classified as the nondownstaged group. Of the total of 86 patients, the mean ADC values before, during, and after pre-CRT (pre ADC, during-ADC, and post-ADC) were (1.03+/-0.17)*10(-3), (1.39+/-0.28)*10(-3), and (1.61+/-0.27)*10(-3) mm(2)/s and there was a significant difference (P<0.001). However, the pre-CRT ADC of the downstaged group did not differ significantly from that of the nondownstaged group (P=0.615). Of the 43 patients who underwent MRI before, during and after pre-CRT, the mean ADC values were (1.05+/-0.16)*10(-3), (1.39+/-0.29)*10(-3)and (1.67+/-0.30)*10(-3) mm(2)/s, respectively, showing a significant difference (P<0.001)as well. CONCLUSIONS: The mean ADC value of rectal cancer is gradually increasing along with the course of chemotherapy. Pre-ADC is not a good parameter to be used to predict the efficacy of pre-CRT for locally advanced rectal cancer. PMID- 26899335 TI - [Efficacy evaluation and exploration of TACE combined with CT-guided precision microwave ablation treatment for primary liver cancer]. AB - OBJECTIVE: To analyze the clinical therapeutic efficacy of transcatheter arterial chemoembolization combined with CT-guided percutaneous precision microwave ablation for the treatment of primary liver cancer and its influencing factors. METHODS: A total of 126 patients with primary liver cancer were treated by transcatheter arterial chemoembolization combined with CT-guided percutaneous precision microwave ablation from Mar 2010 to Oct 2014 in our center. The treatment effect, postoperative complications and recurrence rates were observed, and the factors related to recurrence and survival time were analyzed. RESULTS: All 126 primary liver cancer patients with 201 tumors were ablated for 177 times, and 113 cases with 185 tumors were completed ablated, the complete ablation rate was 92.0%. In all patients, 4 cases had serious complications, the incidence rate was 3.2%. 37 cases had recurrence, with a recurrence rate of 29.4%. All patients were followed up for 10 to 65 months, 17 patients died, and the 1-, 2-, and 3 year cumulative survival rates were 95.2%, 88.1%, and 84.1%, respectively, and the 1-, 2-, and 3-year progression-free-survival rates were 81.5%, 62.7% and 49.2%, respectively .Univariate analysis showed that preoperative AFP level, Child-Pugh score, BCLC stage and the largest tumor size were associated with the survival of patients who received TACE combined with CT-guided precision MWA, and the preoperative AFP level, internal medicine therapy, tumor number and the largest tumor size were associated with the progression-free-survival after the treatment (P<0.05). Multivariate analysis showed that Child-Pugh score and BCLC stage were independent factors affecting the survival of patients with primary liver cancer patients treated with TACE combined with CT guided percutaneous MWA, and the tumor number and the maximum tumor size were independent factors affecting the progression-free-survival of the patients (P<0.05). CONCLUSION: TACE combined with CT-guided percutaneous precision microwave ablation therapy for primary liver cancer has reliable safety and efficacy. PMID- 26899336 TI - [Analysis of characteristics and factors affecting the recurrence of esophageal cancer within the first year after surgery]. AB - OBJECTIVE: To analyze the characteristics and factors affecting the recurrence in esophageal cancer within the first year after esophagectomy. METHODS: We reviewed retrospectively the clinical and follow-up data of 320 patients who underwent surgical treatment from April 2009 to April 2013 in Sichuan Provincial Cancer Hospital. RESULTS: 72 cases (72/320, 22.5%) had tumor recurrence within the first year after surgery. The average recurrence time was 6.89+/-3.53 months and the median recurrence time was 6.02 months. Univariate analysis showed that T stage, N stage, G grade, and pathological stage are related to the recurrence (P<0.05 for all). Logistic regression analysis showed that pathological stage is an independent risk factor for recurrence (P=0.002). There were 46 cases (46/72, 63.9%) of local recurrence and 26 cases (26/72, 36.1%) of distant metastasis. Among the 46 cases of local recurrence, 27 cases (27/46, 58.7%) had upper mediastinal lymph node metastasis. Among the 26 cases of distant metastasis, there were 11 cases (11/26, 42.3%) of pulmonary metastasis. Among the 72 cases of recurrence, the average number of dissected lymph nodes and involved nodes were 29.40+/-11.41 and 4.37+/-5.65, respectively, in patients with distant metastasis, and 21.18+/-10.37 and 1.91+/-2.14, respectively, in patients with local recurrence. Both the number of dissected and involved lymph nodes were significantly higher in the patients with distant metastasis (P<0.05). CONCLUSIONS: Lymph node metastasis is the most common pattern of recent relapse after esophagectomy, and pathological stage is an independent risk factor for recurrence within the first year after surgery. Standardized lymph node dissection and rational treatment strategy is the key measures to reduce early recurrence of esophageal cancer. PMID- 26899338 TI - [Consideration of immune checkpoint inhibitors in cancer therapy]. AB - Immune checkpoint inhibitor targets T-cell regulatory pathways by blocking negative signal to enhance antitumor immune response, and led to anti-tumor effect. This therapy has shown a durable clinical response which can lead part of cancer patients a long survival time. With lessons learned from advanced melanoma, I propose some questions and try to discuss some of them. PMID- 26899337 TI - [Impact of number of dissected lymph nodes on survival in patients with thoracic esophageal squamous cell carcinoma after radical resection]. AB - OBJECTIVE: To evaluate the impact of the number of dissected lymph nodes on survival of patients with stage T3N0M0 thoracic esophageal squamous cell carcinoma (ESCC). METHODS: The clinicopathlogical dada of 249 patients with stage T3N0M0 thoracic ESCC were analyzed retrospectively. The median age of the 249 patients (171 males and 78 females) was 60-year old. The primary lesions were located in the upper- in 40, middle- in 177, and lower-thoracic esophagus in 45 patients. The median length of the lesions was 5 cm (range 2-12 cm). As for the severity of adhesion after surgery, there were 35 with no adhesion, 90 with mild , and 124 patients with severe adhesion. The median number of dissected lymph nodes (dissected LN) at surgery was 9 (range 1-27), among them, less than 6 dissected LNs in 55, 6-11 dissected LNs in 133, and 11 or more dissected LNs in 61 cases. There were 210 patients with moderately or highly, and 39 with poorly differentiated cancer. 98 patients were treated with surgery alone, and 151 with postoperative adjuvant treatment. RESULTS: The follow-up deadline was July 2013. The 1-, 3-, and 5-year overall survival rates were 90.0%, 68.7% and 55.2%, respectively. The 1-, 3-, and 5-year survival rates were 85.5%, 63.6% and 39.1% in patients with <6 dissected LNs, 89.5%, 67.7% and 56.9% in patients with 6-11 dissected LNs, and 95.1%, 75.4% and 66.2% in patients with >11 dissected LNs, respectively (P=0.073). The survival was shorter in patients with <6 dissected LNs than patients with >11 dissected LNs (P=0.022). The subgroup analysis showed that in patients with middle-thoracic ESCC, the length of lesion <=5 cm or mild adhesion after surgery and the number of dissected LNs were associated with survival after surgery. CONCLUSIONS: For patients with stage T3N0M0 thoracic ESCC after surgery, the number of dissected LNs is an important factor affecting the survival, and at least 6 or more lymph nodes should be dissected. If lymphadenectomy is not adequately performed, postoperative adjuvant therapy should be recommend. PMID- 26899339 TI - [An enlarged right tonsil as first manifestation of small cell lung cancer: a case report]. PMID- 26899340 TI - Managing odds in stem cells: insights into the role of mitochondrial antioxidant enzyme MnSOD. AB - Reactive oxygen species (ROS) have been poised at a straddled state of being beneficiary as well detrimental depending on its threshold levels. Maintaining the homeostasis of ROS is imperative for normal cellular physiology, wherein physiological concentrations of ROS are involved in cell signaling and elevated ROS contribute to the development of various diseases. Superoxide dismutases (SODs), enzymes involved in dismutation of superoxide anion to hydrogen peroxide, arrive as a first line of defense when there is perturbation in the homeostasis of ROS. As mitochondria are the main site of superoxide production, among SODs, mitochondrial manganese SOD (MnSOD) is the primary antioxidant enzyme that protects cells from ROS. Most importantly, knockout of MnSOD leads to postnatal lethality and tissue-specific conditional knockout in brain resulted in death of mice, conclusively portraying the essential role of MnSOD in development. Although MnSOD has been extensively discussed with the purview of tumor biology and aging, understanding the crucial role of MnSOD in stem cell physiology is still at its infant stage. Ever increasing progress in stem cell research has recently unveiled the essential role of MnSOD in self-renewal and differentiation of stem cells. In this review, we will conglomerate the current aspects by which MnSOD can contribute to embryonic stem cells' and adult stem cells' functions and interpret the necessity of understanding MnSOD for further stem cell mediated applications. PMID- 26899341 TI - Anti-stress Activity of Ocimum sanctum: Possible Effects on Hypothalamic Pituitary-Adrenal Axis. AB - The present study investigated anti-stress potential of Ocimum sanctum in chronic variable stress (CVS) paradigm. Further, the possible mechanism of anti-stress was explored in vitro using cell and cell-free assays. Rats were administered O. sanctum followed by CVS regimen for a period of 16 days. On days 4, 8, 12, and 16, body weight and immobility time in forced swim test were measured. In addition, the possible inhibitory effect of O. sanctum and ursolic acid on cortisol release and CRHR1 receptor activity were studied in cell-based assays, while inhibitory effects on 11beta-hydroxysteroid dehydrogenase type 1 (11beta HSD1) and catechol-O-methyltransferase (COMT) were studied in cell-free assays. CVS group demonstrated less body weight gain and higher immobility time than O. sanctum administered groups, while oral administration of O. sanctum significantly increased body weight gain and decreased the immobility time. Further, O. sanctum and its constituents inhibited cortisol release and exhibited a significant CRHR1 receptor antagonist activity. Also, they had specific inhibitory activity towards 11beta-HSD1 and COMT activity. Thus, O. sanctum was found to be effective in the management of stress effects, and anti-stress activity could be due to inhibition of cortisol release, blocking CRHR1 receptor, and inhibiting 11beta-HSD1 and COMT activities. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26899342 TI - Functional magnetic resonance imaging confirms forward suppression for rapidly alternating sounds in human auditory cortex but not in the inferior colliculus. AB - Forward suppression at the level of the auditory cortex has been suggested to subserve auditory stream segregation. Recent results in non-streaming stimulation contexts have indicated that forward suppression can also be observed in the inferior colliculus; whether this holds for streaming-related contexts remains unclear. Here, we used cardiac-gated fMRI to examine forward suppression in the inferior colliculus (and the rest of the human auditory pathway) in response to canonical streaming stimuli (rapid tone sequences comprised of either one repetitive tone or two alternating tones). The first stimulus is typically perceived as a single stream, the second as two interleaved streams. In different experiments using either pure tones differing in frequency or bandpass-filtered noise differing in inter-aural time differences, we observed stronger auditory cortex activation in response to alternating vs. repetitive stimulation, consistent with the presence of forward suppression. In contrast, activity in the inferior colliculus and other subcortical nuclei did not significantly differ between alternating and monotonic stimuli. This finding could be explained by active amplification of forward suppression in auditory cortex, by a low rate (or absence) of cells showing forward suppression in inferior colliculus, or both. PMID- 26899343 TI - Morphology and microchemistry of the otoliths of the inner ear of anuran larvae. AB - To navigate in space most vertebrates need precise positional cues provided by a variety of sensors, including structures in the inner ear, which are exquisitely sensitive to gravity and linear acceleration. Although these structures have been described in many vertebrates, no information is available for anuran larvae. The purpose of our study was to describe, for the first time, the size, complexity and microchemistry of the saccular otoliths of the larva of 13 anuran species from central Argentina, using electron microscopy and X-ray spectroscopy (N = 65). We concluded that a) these structures differ in area, perimeter, otolith relative size and fractal dimension, but are similar in terms of their microchemistry when compared by spatial guilds, b) that nektonic species have larger otoliths than nektonic-benthic and benthic species and c) that benthic species have larger otolith relative size than nektonic-benthic and nektonic species. PMID- 26899344 TI - Individual and combined effects of maternal anemia and prenatal infection on risk for schizophrenia in offspring. AB - BACKGROUND: Maternal iron deficiency and infection during pregnancy have individually been associated with increased risk of schizophrenia in the offspring, but possible interactions between the two remain unidentified thus far. Therefore, we determined the individual and combined effects of maternal infection during pregnancy and prepartum anemia on schizophrenia risk in the offspring. METHODS: We conducted a population-based study with individual record linkage of the Danish Civil Registration System, the Danish Hospital Register, and the Central Danish Psychiatric Register. In a cohort of Danish singleton births 1,403,183 born between 1977 and 2002, 6729 developed schizophrenia between 1987 and 2012. Cohort members were considered as having a maternal history of anemia if the mother had received a diagnosis of anemia at any time during the pregnancy. Maternal infection was defined based on infections requiring hospital admission during pregnancy. RESULTS: Maternal anemia and infection were both associated with increased risk of schizophrenia in unadjusted analyses (1.45-fold increase for anemia, 95% CI: 1.14-1.82; 1.32-fold increase for infection, 95% CI: 1.17-1.48). The effect of maternal infection remained significant (1.16-fold increase, 95% CI: 1.03-1.31) after adjustment for possible confounding factors. Combined exposure to anemia and an infection increased the effect size to a 2.49 fold increased schizophrenia risk (95% CI: 1.29-4.27). The interaction analysis, however, failed to provide evidence for multiplicative interactions between the two factors. CONCLUSION: Our findings indicate that maternal anemia and infection have additive but not interactive effects, and therefore, they may represent two independent risk factors of schizophrenia. PMID- 26899345 TI - A network of synaptic genes associated with schizophrenia and bipolar disorder. AB - Identification of novel candidate genes for schizophrenia (SZ) and bipolar disorder (BP), two psychiatric disorders with large epidemiological impacts, is a key research area in neurosciences and psychiatric genetics. Previous evidence from genome-wide studies suggests an important role for genes involved in synaptic plasticity in the risk for SZ and BP. We used a convergent genomics approach, combining different lines of biological evidence, to identify genes involved in the cAMP/PKA/CREB functional pathway that could be novel candidates for BP and SZ: CREB1, CREM, GRIN2C, NPY2R, NF1, PPP3CB and PRKAR1A. These 7 genes were analyzed in a HapMap based association study comprising 48 common SNPs in 486 SZ, 351 BP patients and 514 control individuals recruited from an isolated population in Northern Sweden. Genetic analysis showed significant allelic associations of SNPs in PRKAR1A with SZ and of PPP3CB and PRKAR1A with BP. Our results highlight the feasibility and the importance of convergent genomic data analysis for the identification of candidate genes and our data provide support for the role of common inherited variants in synaptic genes and their involvement in the etiology of BP and SZ. PMID- 26899346 TI - A new delimitation of the Afro-Eurasian plant genus Althenia to include its Australasian relative, Lepilaena (Potamogetonaceae) - Evidence from DNA and morphological data. AB - Althenia (Potamogetonaceae) is an aquatic plant genus disjunctly distributed in the southern- (South Africa's Cape Floristic Region: CFR) and northern- (Mediterranean Eurasia) hemispheres. This genus and its Australasian relative, Lepilaena, share similar floral characters yet have been treated as different genera or sections of Althenia sensu lato (s.l.) due to the isolated geographic distribution as well as the differences in sex expression, stamen construction, and stigma morphology. The diagnostic characters, however, need reevaluation over the boundaries between the entities. Here we tested the taxonomic delimitation between the entities, assessed synapomorphies for evolutionary lineages, and inferred biogeographic history in a phylogenetic framework. Our results indicated that Lepilaena was resolved as non-monophyletic in both plastid DNA and nuclear PhyC trees and Althenia was nested within it. As Althenia has nomenclatural priority, we propose a new delimitation to recognize Althenia s.l., which can be diagnosed by the female flowers with 3-segmented perianths and male flowers with perianths. The previously used diagnostic characters are either autapomorphies or synapomorphies for small lineages within Althenia s.l., and evolutionary transitions to sessile female flowers and narrow leaves characterize larger clades. Biogeographic analyses suggested a Miocene origin of Althenia s.l. in Australasia and indicated at least one inter- and one intra-specific inter continental dispersal events among Australasia, Mediterranean Eurasia, and CFR need to be hypothesized to explain the current distribution patterns. PMID- 26899348 TI - Demographic characteristics and seasonal variations of acute appendicitis. AB - BACKGROUND: The most common disease required emergency surgical operation is acute appendicitis. Appendectomy is the most common surgical procedure in the world and remains important due to be an efficient treatment method. We aimed to determine seasonal variations of acute appendicitis in our regions and identify the demographical and regional differences. METHODS: We analyzed retrospectively data of the patients who were admitted to the Afyon Kocatepe University hospital and Sivrihisar State hospital between 2003 and 2012. 839 patients' data were analyzed. RESULTS: Mean age of the all patients was 33 +/- 14.7 year. Acute appendicitis was seen more frequent in autumn and spring (P > 0.05). There was no significant difference between seasons in Afyon Kocatepe university hospital, while appendicitis was seen more common in autumn than winter in Sivrihisar state hospital (P < 0.05). There was not any relationship with the monthly average temperature, humidity, total precipitation amount and frequency of appendicitis (P > 0.05). CONCLUSION: Although appendicitis has a seasonal variation, other environmental factors and impact of nutritional habit should not be ignored. Etiology of appendicitis is still multifactorial. In the future multiparameter nationwide studies can present country-specific etiology of appendicitis. KEY WORDS: Appendectomy, Appendicitis, Seasonal variations. PMID- 26899350 TI - Black phosphorene/monolayer transition-metal dichalcogenides as two dimensional van der Waals heterostructures: a first-principles study. AB - The electronic structure of black phosphorene (BP)/monolayer 1H-XT2 (X = Mo, W; T = S, Se, Te) two dimensional (2D) van der Waals heterostructures have been calculated by the first-principles method. It is found that the electronic band structures of both BP and XT2 are preserved in the combined van der Waals heterostructures. The WSe2/BP van der Waals heterostructure demonstrates a type-I band alignment, but the MoS2/BP, MoSe2/BP, MoTe2/BP, WS2/BP and WTe2/BP van der Waals heterostructures demonstrate a type-II band alignment. In particular, the n type XT2/p-type BP van der Waals heterostructures can be applied in p-n diode and logical devices. Strong spin splitting appears in all of the heterostructures when considering the spin orbital coupling. Our results play a significant role in the prediction of novel 2D van der Waals heterostructures that have potential applications in spin-filter devices, spin field effect transistors, optoelectronic devices, etc. PMID- 26899351 TI - Evidence for a stabilization of incidence rates for base of tongue and tonsil carcinoma in the U.S. white population. PMID- 26899349 TI - One CNV Discordance in NRXN1 Observed Upon Genome-wide Screening in 38 Pairs of Adult Healthy Monozygotic Twins. AB - Monozygotic (MZ) twins stem from the same single fertilized egg and therefore share all their inherited genetic variation. This is one of the unequivocal facts on which genetic epidemiology and twin studies are based. To what extent this also implies that MZ twins share genotypes in adult tissues is not precisely established, but a common pragmatic assumption is that MZ twins are 100% genetically identical also in adult tissues. During the past decade, this view has been challenged by several reports, with observations of differences in post zygotic copy number variations (CNVs) between members of the same MZ pair. In this study, we performed a systematic search for differences of CNVs within 38 adult MZ pairs who had been misclassified as dizygotic (DZ) twins by questionnaire-based assessment. Initial scoring by PennCNV suggested a total of 967 CNV discordances. The within-pair correlation in number of CNVs detected was strongly dependent on confidence score filtering and reached a plateau of r = 0.8 when restricting to CNVs detected with confidence score larger than 50. The top ranked discordances were subsequently selected for validation by quantitative polymerase chain reaction (qPCR), from which one single ~120kb deletion in NRXN1 on chromosome 2 (bp 51017111-51136802) was validated. Despite involving an exon, no sign of cognitive/mental consequences was apparent in the affected twin pair, potentially reflecting limited or lack of expression of the transcripts containing this exon in nerve/brain. PMID- 26899347 TI - Modulation of Toll-like receptor signaling in innate immunity by natural products. AB - For centuries, natural products and their derivatives have provided a rich source of compounds for the development of new immunotherapies in the treatment of human disease. Many of these compounds are currently undergoing clinical trials, particularly as anti-oxidative, anti-microbial, and anti-cancer agents. However, the function and mechanism of natural products in how they interact with our immune system has yet to be extensively explored. Natural immune modulators may provide the key to control and ultimately defeat disorders affecting the immune system. They can either up- or down-regulate the immune response with few undesired adverse effects. In this review, we summarize the recent advancements made in utilizing natural products for immunomodulation and their important molecular targets, members of the Toll-like receptor (TLR) family, in the innate immune system. PMID- 26899352 TI - Simeprevir or telaprevir with peginterferon and ribavirin for recurrent hepatitis C after living-donor liver transplantation: A Japanese multicenter experience. AB - AIM: This study aimed to clarify the efficacy and safety of simeprevir, a second generation NS3/4A inhibitor, with peginterferon and ribavirin for recurrent hepatitis C after liver transplantation. METHODS: A retrospective cohort study of living-donor liver transplant recipients with recurrent hepatitis C with the hepatitis C virus genotype 1 treated with either simeprevir- or telaprevir-based triple therapy was carried out at eight Japanese liver transplant centers. RESULTS: Simeprevir- and telaprevir-based triple therapies were given to 79 and 36 patients, respectively. Of the 79 patients treated with simeprevir-based triple therapy, 44 (56%) achieved sustained virological response 12 weeks (SVR12) after treatment ended, and there was no significant difference in the SVR12 between the simeprevir- and telaprevir-based triple therapy groups (69%). The rates of adverse events were not significantly different between the simeprevir- and telaprevir-based triple therapy groups, although the rate of patients who received blood cell transfusion and erythropoietin due to anemia and had renal insufficiency were significantly higher in the telaprevir group than in the simeprevir group. Three baseline factors, the presence of prior dual therapy with peginterferon and ribavirin (P = 0.001), a non-responder to the prior dual therapy (P < 0.001), and male sex (P = 0.040), were identified as significant predictive factors for non-SVR with simeprevir-based triple therapy. CONCLUSION: Simeprevir-based triple therapy for recurrent hepatitis C after living-donor liver transplantation resulted in a high SVR rate and good tolerability, especially in treatment-naive patients. PMID- 26899354 TI - Varying activity of chlorhexidine-based disinfectants against Klebsiella pneumoniae clinical isolates and adapted strains. AB - BACKGROUND: Control of multi-drug-resistant (MDR) organisms relies increasingly on the use of biocides, including chlorhexidine, to limit the risk of infection. The concentration and formulation of chlorhexidine can vary hugely between products. AIM: To establish the activity of chlorhexidine and in-use chlorhexidine formulations against 14 clinical Klebsiella pneumoniae strains isolated before and since the use of chlorhexidine became routine, and strains that have adapted following sublethal chlorhexidine exposure. METHODS: Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of five chlorhexidine-containing formulations were measured at 5min, 15min, 30min and 24h for the panel of K. pneumoniae strains. FINDINGS: After 5min, MBCs of five formulations varied from 0.006 to >50% working concentration (WC) or from 78 to 2500MUg/mL chlorhexidine. For one formulation, MBCs were >50% WC for five of the 14 strains, and for another formulation, four of the 14 strains could resist 25% WC. NCTC 13368 was consistently most tolerant to chlorhexidine, whereas the strains isolated before the use of chlorhexidine became routine were more sensitive. One pre-chlorhexidine era and five modern strains increased MICs up to 16-fold following exposure to sublethal concentrations of chlorhexidine. A hand disinfectant with MBCs of 0.39% WC for all six of the wild-type strains, had MBCs of 50% WC for the chlorhexidine-adapted strains. CONCLUSION: Not all chlorhexidine formulations kill MDR K. pneumoniae after the recommended exposure time. Activity, especially against chlorhexidine-adapted strains, depends on additional ingredients. Careful formulation of chlorhexidine products is therefore important to maintain and enhance the activity of chlorhexidine products, and avoid potential breakdown in infection control. PMID- 26899353 TI - Graphene oxide-dependent growth and self-aggregation into a hydrogel complex of exoelectrogenic bacteria. AB - Graphene oxide (GO) is reduced by certain exoelectrogenic bacteria, but its effects on bacterial growth and metabolism are a controversial issue. This study aimed to determine whether GO functions as the terminal electron acceptor to allow specific growth of and electricity production by exoelectrogenic bacteria. Cultivation of environmental samples with GO and acetate as the sole substrate could specifically enrich exoelectrogenic bacteria with Geobacter species predominating (51-68% of the total populations). Interestingly, bacteria in these cultures self-aggregated into a conductive hydrogel complex together with biologically reduced GO (rGO). A novel GO-respiring bacterium designated Geobacter sp. strain R4 was isolated from this hydrogel complex. This organism exhibited stable electricity production at >1000 MUA/cm(3) (at 200 mV vs Ag/AgCl) for more than 60 d via rGO while temporary electricity production using graphite felt. The better electricity production depends upon the characteristics of rGO such as a large surface area for biofilm growth, greater capacitance, and smaller internal resistance. This is the first report to demonstrate GO-dependent growth of exoelectrogenic bacteria while forming a conductive hydrogel complex with rGO. The simple put-and-wait process leading to the formation of hydrogel complexes of rGO and exoelectrogens will enable wider applications of GO to bioelectrochemical systems. PMID- 26899356 TI - Coexistent arteriovenous malformation and hippocampal sclerosis. AB - Cavernous angiomas or cavernomas have been occasionally described in patients presenting with medically intractable epilepsy. Reports of cavernomas associated with a second pathology potentially causative of seizures have rarely been documented; most commonly, the second pathology is focal cortical dysplasia or less frequently, hippocampal sclerosis. To our knowledge, cases of arteriovenous malformation arising in this clinical setting and associated with hippocampal sclerosis have not been previously described. We report a 56-year-old woman who initially presented at age 24years with staring spells. Imaging studies revealed an arteriovenous malformation in the right parietal lobe. At age 51years, she represented with signs and symptoms related to a hemorrhage from the malformation. The patient underwent Gamma Knife radiosurgery (Elekta AB, Stockholm, Sweden) of the lesion. She subsequently developed seizures, refractory to medical management. MRI studies showed atrophy in the right hippocampus. She underwent resection of the right parietal lobe and hippocampus. Histopathologic examination of the right parietal lesion revealed an arteriovenous malformation marked by focally prominent vascular sclerosis, calcification and adjacent hemosiderin deposition. The hippocampus was marked by prominent neuronal loss and gliosis in the CA1 region, consistent with CA1 sclerosis or hippocampal sclerosis International League Against Epilepsy type 2. PMID- 26899357 TI - Diagnosing acute lacunar infarction using CT perfusion. AB - The value of CT perfusion (CTP) in detecting acute lacunar infarcts (LACI) has not been well established. We tested the sensitivity of CTP for LACI. CTP maps of consecutive stroke patients from 2009-2013 were examined. MRI diffusion imaging was used to identify those with LACI. Two stroke neurologists independently evaluated the CTP maps for evidence of a perfusion lesion in a deep perforating artery territory. Cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT) and time to maximum (Tmax) maps were first examined in isolation and then in combination. Inter-observer agreement was measured using Cohen's kappa. The lesions identified were later confirmed against the diffusion MRI reference and the sensitivity and specificity of CTP maps calculated. A total of 63 patient scans were analysed. There were 32 patients with MRI-confirmed LACI within the coverage of CTP; 18 in the striatum, 10 thalamic, and four in the corona radiata. Another 31 patients had normal MRI. Inter-rater agreement was good (kappa=0.83). Sensitivity (blinded consensus) was highest for MTT (56.2%) compared to Tmax (25%, p<0.001), CBV (9.3%, p=0.021) and CBF (43.7%, p<0.001). MTT maps enable detection of a significant proportion of LACI using CTP. PMID- 26899358 TI - Respiratory failure as the presenting manifestation of amyotrophic lateral sclerosis. AB - Although amyotrophic lateral sclerosis (ALS) does not directly affect the lung parenchyma, it can jeopardize the mechanical function of the respiratory system. About one-quarter of ALS patients have had at least one prior misdiagnosis. Therefore, a high clinical suspicion, and careful correlation of physical examination and electromyography (EMG) are needed to reach the correct diagnosis. We report a 65-year-old man who presented with a progressive exertional dyspnea. He was subsequently found to have a diaphragmatic paralysis that was felt to be secondary to spinal cord stenosis. However, his subsequent EMG showed evidence of muscle fasciculation and he was ultimately diagnosed with ALS. PMID- 26899359 TI - MR imaging in nelarabine-induced myelopathy. AB - Nelarabine is one of the newer and novel drugs approved by the USA Food and Drug Administration for treatment of relapsed and resistant acute lymphoblastic leukemia. Although there are a few accounts of the neurologic toxicity of nelarabine in the oncological literature, it has never been discussed from a radiologic stand point to our knowledge. We describe a case of nelarabine-induced myelopathy and review the existing literature in an attempt to characterize the MRI features helpful in making an early diagnosis of this elusive entity. PMID- 26899355 TI - 2015 ACVIM Small Animal Consensus Statement on Seizure Management in Dogs. AB - This report represents a scientific and working clinical consensus statement on seizure management in dogs based on current literature and clinical expertise. The goal was to establish guidelines for a predetermined, concise, and logical sequential approach to chronic seizure management starting with seizure identification and diagnosis (not included in this report), reviewing decision making, treatment strategies, focusing on issues related to chronic antiepileptic drug treatment response and monitoring, and guidelines to enhance patient response and quality of life. Ultimately, we hope to provide a foundation for ongoing and future clinical epilepsy research in veterinary medicine. PMID- 26899360 TI - An ecological method to understand agricultural standardization in peach orchard ecosystems. AB - While the worldwide standardization of agricultural production has been advocated and recommended, relatively little research has focused on the ecological significance of such a shift. The ecological concerns stemming from the standardization of agricultural production may require new methodology. In this study, we concentrated on how ecological two-sidedness and ecological processes affect the standardization of agricultural production which was divided into three phrases (pre-, mid- and post-production), considering both the positive and negative effects of agricultural processes. We constructed evaluation indicator systems for the pre-, mid- and post-production phases and here we presented a Standardization of Green Production Index (SGPI) based on the Full Permutation Polygon Synthetic Indicator (FPPSI) method which we used to assess the superiority of three methods of standardized production for peaches. The values of SGPI for pre-, mid- and post-production were 0.121 (Level IV, "Excellent" standard), 0.379 (Level III, "Good" standard), and 0.769 * 10(-2) (Level IV, "Excellent" standard), respectively. Here we aimed to explore the integrated application of ecological two-sidedness and ecological process in agricultural production. Our results are of use to decision-makers and ecologists focusing on eco-agriculture and those farmers who hope to implement standardized agricultural production practices. PMID- 26899361 TI - Tetrandrine--A molecule of wide bioactivity. AB - Stephania tetrandra and other related species of Menispermaceae form the major source of the bisbenzylisoquinoline alkaloid - tetrandrine. The plant is extensively referenced in the Chinese Pharmacopoeia for its use in the Chinese medicinal system as an analgesic and diuretic agent and also in the treatment of hypertension and various other ailments, including asthma, tuberculosis, dysentery, hyperglycemia, malaria, cancer and fever. Tetrandrine, well-known to act as a calcium channel blocker, has been tested in clinical trials and found effective against silicosis, hypertension, inflammation and lung cancer without any toxicity. Recently, the efficacy of tetrandrine was tested against Mycobaterium tuberculosis, Candida albicans, Plasmodium falciparum and Ebola virus. Tetrandrine's pharmacological property has been proved to be through its action on different signalling pathways like reactive oxygen species, enhanced autophagic flux, reversal of multi drug resistance, caspase pathway, cell cycle arrest and by modification of calcium channels. The present review summarises current knowledge on the synthesis, distribution, extraction, structural elucidation, pharmacological properties and the mechanism of action of tetrandrine. Future perspectives in the clinical use of tetrandrine as a drug are also considered. PMID- 26899362 TI - Biological activity of ellagitannins: Effects as anti-oxidants, pro-oxidants and metal chelators. AB - Ellagitannins are a subclass of hydrolysable tannins that have been suggested to function as defensive compounds of plants against herbivores. However, it is known that the conditions in the digestive tracts of different herbivores are variable, so it seems reasonable to anticipate that the reactivities and modes of actions of these ingested defensive compounds would also be different. A previous study on a few ellagitannins has shown that these polyphenolic compounds are highly oxidizable at high pH and that their bioactivity can be attributed to certain structural features. Herein, the activities of 13 ellagitannins using the deoxyribose assay were measured. The results provided information about the anti oxidant, pro-oxidant and metal chelating properties of ellagitannins. Surprisingly, many of the tested ellagitannins exhibited pro-oxidant activities even at neutral pH and only moderate to low radical scavenging activities, although the metal chelating capacities of all tested ellagitannins were relatively high. PMID- 26899363 TI - Benchtop Whole-Genome Sequencing for Identification of Nosocomial Outbreaks in Tanzania. PMID- 26899365 TI - Multiple detection of single nucleotide polymorphism by microarray-based resonance light scattering assay with enlarged gold nanoparticle probes. AB - The mapping of specific single nucleotide polymorphisms (SNPs) in patients' genome is a critical process for the development of personalized therapy. In this work, a DNA microarray-based resonance light scattering (RLS) assay has been developed for multiplexed detection of breast cancer related SNPs with high sensitivity and selectivity. After hybridization of the desired target single stranded DNAs (ssDNAs) with the ssDNA probes on a microarray, the polyvalent ssDNA modified 13 nm gold nanoparticles (GNPs) are employed to label the hybridization reaction through the formation of a three-stranded DNA system. The H2O2-mediated enlargement of GNPs is then used to enhance the RLS signal. The microarray-based RLS assay provides a detection limit of 10 pM (S/N = 3) for the target ssDNA and determines an allele frequency as low as 1.0% in the target ssDNA cocktail. Combined with an asymmetric PCR technique, the proposed assay shows good accuracy and sensitivity in profiling 4 SNPs related to breast cancer of three selected cell lines. PMID- 26899364 TI - Chemical Vapor Deposition of Monolayer Mo(1-x)W(x)S2 Crystals with Tunable Band Gaps. AB - Band gap engineering of monolayer transition metal dichalcogenides, such as MoS2 and WS2, is essential for the applications of the two-dimensional (2D) crystals in electronic and optoelectronic devices. Although it is known that chemical mixture can evidently change the band gaps of alloyed Mo(1-x)W(x)S2 crystals, the successful growth of Mo(1-x)W(x)S2 monolayers with tunable Mo/W ratios has not been realized by conventional chemical vapor deposition. Herein, we developed a low-pressure chemical vapor deposition (LP-CVD) method to grow monolayer Mo(1 x)W(x)S2 (x = 0-1) 2D crystals with a wide range of Mo/W ratios. Raman spectroscopy and high-resolution transmission electron microscopy demonstrate the homogeneous mixture of Mo and W in the 2D alloys. Photoluminescence measurements show that the optical band gaps of the monolayer Mo(1-x)W(x)S2 crystals strongly depend on the Mo/W ratios and continuously tunable band gap can be achieved by controlling the W or Mo portion by the LP-CVD. PMID- 26899366 TI - Analysis of the diagnostic efficiency of serum oxidative stress parameters in patients with breast cancer at various clinical stages. AB - BACKGROUND: Reactive oxygen species (ROS) are balanced through enzymatic mechanisms and exogenous antioxidants; imbalance results in oxidative stress (OxS). It is known that OxS plays an important role in the occurrence, development, and metastasis of breast cancer. The present study aimed to assess serum total oxidant status (TOS), total antioxidant status (TAS), and oxidant stress index (OSI) in patients at different clinical stages of breast cancer and to evaluate their diagnostic accuracy. METHODS: Serum TOS, TAS, and OSI were determined in 91 patients with breast cancer at different stages, 51 patients with benign breast tumors, and 35 healthy adults. RESULTS: Significant differences in serum TOS (F=104.384, p=0.000), TAS (F=18.247, p=0.000), and OSI (F=62.598, p=0.000) were observed among the 3 groups (benign breast tumor patients, breast cancer patients, and healthy women). Of the enrolled breast cancer patients, significant differences were also observed among different tumor stages, with TOS and OSI gradually increasing as the disease progressed, while TAS diminished. Receiver operating characteristic curve analysis revealed that the area under the ROC curve for OSI (AUCOSI) was significantly higher than AUCTAS (z=2.344, p=0.019) in distinguishing breast cancer from control groups (including disease control and the healthy control). The AUCOSI (z=4.700, p=0.001) or AUCTOS (z=4.700, p=0.001) was significantly higher than AUCTAS in distinguishing breast cancer from the healthy control. The AUCOSI (z=5.907, p=0.000) or AUCTOS (z=5.667, p=0.000) was significantly higher than AUCTAS in distinguishing benign breast tumors from the healthy control. CONCLUSION: Oxidative stress parameters might serve as important indexes for monitoring breast cancer occurrence and progression. The combined evaluation of TOS, TAS, and OSI could be more beneficial for clinical assessment. PMID- 26899368 TI - Proteolysis in meat tenderization from the point of view of each single protein: A proteomic perspective. AB - Muscle has to undergo a number of biochemical changes to become the final product, and, once become meat, needs to develop the proper organoleptic peculiarities, including tenderness. Tenderness depends on multiple factors, intervening throughout the production chain, from animal's birth till the end of meat aging. Given the striking number of variables, it is not an exaggeration to affirm that meat coming from each individual is a 'unique' meat. So, the process of meat tenderization follows different paths; meat derived from different animals shows its own evolution, but underneath the wide variability, all these individual developments follow a standard template: in other words, there are some boundaries that limit the possible variations. This review wants to give a comprehensive idea of the concept of meat tenderness, in particular focusing on the two protein classes that are among the most important direct responsibles for tenderization: sarcomeric proteins and proteolytic enzymes. We will review the most recent and significant data acquired on each protein, pointing the attention on the results collected by means of the 'omics' technologies, and underlining the possible role of markers in the frame of meat tenderness. BIOLOGICAL SIGNIFICANCE: Our review discusses the evidences collected by means of the 'omics' technologies about the proteolytic mechanisms that act in the muscle-to meat conversion process, leading the muscle to reach the acceptable tenderness of the eatable meat. We consider the proteolytic enzymes and their substrate individually, summarizing the most significant data from the omic approach, and discussing their possible role of marker of tenderness. PMID- 26899367 TI - No rapid audiovisual recalibration in adults on the autism spectrum. AB - Autism spectrum disorders (ASD) are characterized by difficulties in social cognition, but are also associated with atypicalities in sensory and perceptual processing. Several groups have reported that autistic individuals show reduced integration of socially relevant audiovisual signals, which may contribute to the higher-order social and cognitive difficulties observed in autism. Here we use a newly devised technique to study instantaneous adaptation to audiovisual asynchrony in autism. Autistic and typical participants were presented with sequences of brief visual and auditory stimuli, varying in asynchrony over a wide range, from 512 ms auditory-lead to 512 ms auditory-lag, and judged whether they seemed to be synchronous. Typical adults showed strong adaptation effects, with trials proceeded by an auditory-lead needing more auditory-lead to seem simultaneous, and vice versa. However, autistic observers showed little or no adaptation, although their simultaneity curves were as narrow as the typical adults. This result supports recent Bayesian models that predict reduced adaptation effects in autism. As rapid audiovisual recalibration may be fundamental for the optimisation of speech comprehension, recalibration problems could render language processing more difficult in autistic individuals, hindering social communication. PMID- 26899369 TI - Can we link emotional eating with the emotion regulation skills of adolescents? AB - OBJECTIVE: A recent cross-sectional study showed that maternal rejection is associated with emotional eating of obese youngsters seeking treatment, and that this relation is mediated by maladaptive emotion regulation (ER) of the youngsters. We wanted to build on this study and investigate the relation between parental rejection, maladaptive ER and emotional eating in a community sample using longitudinal data. DESIGN: Participants were 81 youngsters between the ages of 10 and 16 years. Participants completed questionnaires assessing maternal and paternal rejection, ER strategies and emotional eating, at two time moments (M = 71 days between time moments). Latent change models were used to estimate level and change of each variable. RESULTS: Results showed that the levels of maternal rejection, maladaptive ER and emotional eating were related. The indirect effect of the level of maternal rejection on the level of emotional eating through the level of maladaptive ER was marginally significant. On average, maternal rejection showed no change over time, whereas the other variables decreased. The changes in the variables were not related. CONCLUSION: The findings highlight the importance of assessing the emotional bond between mother and youngster and the ER of youngsters with an emotional eating style. PMID- 26899370 TI - AIDS impact special issue 2015: interpersonal factors associated with HIV partner disclosure among HIV-infected people in China. AB - HIV partner disclosure may facilitate social support, improve psychological well being among HIV-infected individuals, and promote HIV testing and HIV prevention among their sexual partners. A growing literature emphasizes the critical role of interpersonal factors may play in decision-making and practice regarding HIV partner disclosure. However, there is a dearth of empirical studies that investigate how interpersonal factors may be associated with HIV partner disclosure. Using cross-sectional data collected from 791 HIV-infected people in Guangxi China, we examined the associations between these two interpersonal factors (quality of relationship with partner and family communication) and HIV partner disclosure. Descriptive analysis, t-test analysis, and gender stratified GLM analysis were conducted. We find that disclosing HIV status to partners was significantly related to better quality of relationship with partners and open and effective family communication. Gender and partner HIV status might moderate the associations between interpersonal factors and HIV partner disclosure. Our findings suggest the importance of considering relationship quality and enhancing open and comfortable family communication in HIV disclosure interventions. Gender difference and partner HIV status should be also considered in HIV disclosure intervention to address the diverse needs of HIV-infected people. PMID- 26899372 TI - The effectiveness of pneumococcal polysaccharide vaccine 23 (PPV23) in the general population of 50 years of age and older: A systematic review and meta analysis. AB - Two pneumococcal vaccines currently exist and have been recommended for the prevention of pneumococcal infection in adults 65 years of age and older: the 23 valent polysaccharide (PPV23) and the conjugate 13-valent (PCV13) vaccine. OBJECTIVE: To evaluate and summarize the results from all studies reporting on the vaccine effectiveness of PPV23 in preventing invasive pneumococcal disease (IPD) and community-acquired pneumonia (CAP) in individuals over the age of 50. METHODS: Systematic database searches were completed in PubMed, Medline, Embase, CINAHL, Web of Science, and Cochrane. Google Scholar and hand searches of seminal articles and past systematic reviews were employed. Studies were included if they independently evaluated the effect of PPV23 on IPD and/or CAP in adults (50+). Data extraction and quality assessment were both completed independently by two researchers. Quality was assessed using the National Advisory Committee on Immunization methodology for quality assessment. All conflicts were resolved by consensus. RESULTS: The vaccine effectiveness for PPV23 in preventing IPD was 50% (95% CI: 21%-69%) for cohort studies and 54% (95% CI: 32%-69%) for case-control studies. The VE estimates for CAP were 4% (95% CI: -26%-26%) for trials, 17% (95% CI: -26%-45%) for cohort studies, and 7% (95% CI: -10%-21%) for case-control studies. CONCLUSIONS: The vaccine effectiveness of PPV23 in preventing IPD and all-cause CAP was consistent with past systematic reviews and similar to the estimates that were reported in the CAPiTA trial evaluating the vaccine effectiveness of PCV13. Consistent benefits were also reported across ecological studies and reports of surveillance data for the general population 50 years and older. The results suggests that the current practice of vaccinating the adults 65 years of age and older with PPV23 would have similar benefits to PCV13 in preventing potential cases of all-serotype IPD and all-cause CAP. PMID- 26899373 TI - Delta-pgm, a new live-attenuated vaccine against Brucella suis. AB - Brucellosis is one of the most widespread zoonosis in the world affecting many domestic and wild animals including bovines, goats, pigs and dogs. Each species of the Brucella genus has a particular tropism toward different mammals being the most relevant for human health Brucella abortus, Brucella melitensis and Brucella suis that infect bovines, goats/camelids and swine respectively. Although for B. abortus and B. melitensis there are vaccines available, there is no efficient vaccine to protect swine from B. suis infection so far. We describe here the construction of a novel vaccine strain that confers excellent protection against B. suis in a mouse model of infection. This strain is a clean deletion of the phosphoglucomutase (pgm) gene that codes for a protein that catalyzes the conversion of glucose-6-P to glucose-1-P, which is used as a precursor for the biosynthesis of many polysaccharides. The Delta-pgm strain lacks a complete lipopolysaccharide, is unable to synthesize cyclic beta glucans and is sensitive to several detergents and Polymyxin B. We show that this strain replicates in cultured cells, is completely avirulent in the mouse model of infection but protects against a challenge of the virulent strain inducing the production of pro-inflammatory cytokines. This novel strain could be an excellent candidate for the control of swine brucellosis, a disease of emerging concern in many parts of the world. PMID- 26899371 TI - High-throughput proteomics reveal alarmins as amplifiers of tissue pathology and inflammation after spinal cord injury. AB - Spinal cord injury is characterized by acute cellular and axonal damage followed by aggressive inflammation and pathological tissue remodelling. The biological mediators underlying these processes are still largely unknown. Here we apply an innovative proteomics approach targeting the enriched extracellular proteome after spinal cord injury for the first time. Proteomics revealed multiple matrix proteins not previously associated with injured spinal tissue, including small proteoglycans involved in cell-matrix adhesion and collagen fibrillogenesis. Network analysis of transcriptomics and proteomics datasets uncovered persistent overexpression of extracellular alarmins that can trigger inflammation via pattern recognition receptors. In mechanistic experiments, inhibition of toll like receptor-4 (TLR4) and the receptor for advanced glycation end-products (RAGE) revealed the involvement of alarmins in inflammatory gene expression, which was found to be dominated by IL1 and NFkappaBeta signalling. Extracellular high-mobility group box-1 (HMGB1) was identified as the likely endogenous regulator of IL1 expression after injury. These data reveal a novel tissue remodelling signature and identify endogenous alarmins as amplifiers of the inflammatory response that promotes tissue pathology and impedes neuronal repair after spinal cord injury. PMID- 26899374 TI - Factors affecting uptake of influenza vaccination among family physicians. AB - AIM: The aim of this study was to determine the factors that influenced the decisions of family physicians working in primary care health services to receive influenza vaccines. METHODS: This cross-sectional study was performed between June 2014 and September 2014. Physicians were reached electronically via e-mail. A self-reported questionnaire consisting of 50 items covering potential factors that may have influenced their decision to receive vaccination, including perceived risk, severity of the perceived risk, perceived benefit, perceived barriers, cues to action, attitudes, social influences and personal efficacy, was administered to the study participants. Cronbach's alpha for the questionnaire was determined to be 0.92 in the pilot study. RESULTS: The response rate was 27.5% (n=596). Regularly vaccinated physicians accounted for 27.3% of the responses. The median age was 41.84+/-7.80, and the median working duration of the group was 17.0+/-7.8years. The factors that led to increased vaccination compliance (p<0.05) included working duration, age, chronic disease history and living with a person over 65years. Nearly all major domains, i.e., perceived risk, severity of the perceived risk, perceived benefit, perceived barriers, attitudes, social influences and personal efficacy, there were differences between the compliant and noncompliant groups. Multi-regression analyses revealed that risk perception, organizational factors such as time and convenient vaccination increased vaccine compliance. However, the perceived necessity to be vaccinated annually had a negative effect on vaccination behaviour (p<0.05). CONCLUSION: Strategies aimed to increase the flu vaccination ratio among physicians that do not take different factors into account are more likely to be unsuccessful. In the planning and implementation of strategies aiming to increase the vaccination ratio among physicians, it is both necessary and important to take into account behavioural and organizational factors. PMID- 26899375 TI - Cost-effectiveness analysis of universal maternal immunization with tetanus diphtheria-acellular pertussis (Tdap) vaccine in Brazil. AB - BACKGROUND: Pertussis incidence has increased significantly in Brazil since 2011, despite high coverage of whole-cell pertussis containing vaccines in childhood. Infants <4 months are most affected. This study aimed to evaluate the cost effectiveness of introducing universal maternal vaccination with tetanus diphtheria-acellular pertussis vaccine (Tdap) into the National Immunization Program in Brazil. METHODS: Economic evaluation using a decision tree model comparing two strategies: (1) universal vaccination with one dose of Tdap in the third trimester of pregnancy and (2) current practice (no pertussis maternal vaccination), from the perspective of the health system and society. An annual cohort of newborns representing the number of vaccinated pregnant women were followed for one year. Vaccine efficacy were based on literature review. Epidemiological, healthcare resource utilization and cost estimates were based on local data retrieved from Brazilian Health Information Systems. Costs of epidemiological investigation and treatment of contacts of cases were included in the analysis. No discount rate was applied to costs and benefits, as the temporal horizon was one year. Primary outcome was cost per life year saved (LYS). Univariate and best- and worst-case scenarios sensitivity analysis were performed. RESULTS: Maternal vaccination of one annual cohort, with vaccine effectiveness of 78%, and vaccine cost of USD$12.39 per dose, would avoid 661 cases and 24 infant deaths of pertussis, save 1800 years of life and cost USD$28,942,808 and USD$29,002,947, respectively, from the health system and societal perspective. The universal immunization would result in ICERs of USD$15,608 and USD$15,590 per LYS, from the health system and societal perspective, respectively. In sensitivity analysis, the ICER was most sensitive to discounting of life years saved, variation in case-fatality, disease incidence, vaccine cost, and vaccine effectiveness. CONCLUSION: The results indicate that universal maternal immunization with Tdap is a cost-effective intervention for preventing pertussis cases and deaths in infants in Brazil. PMID- 26899376 TI - Efficacy of 23-valent pneumococcal polysaccharide vaccine in preventing community acquired pneumonia among immunocompetent adults: A systematic review and meta analysis of randomized trials. AB - BACKGROUND: Data on the efficacy of the 23-valent pneumococcal polysaccharide vaccine (PPV-23) in preventing adult community-acquired pneumonia (CAP) among the target population of individuals aged over 65 years and high-risk individuals aged 19-64 years are conflicting. As the Advisory Committee on Immunization Practices (ACIP) has recently demonstrated PPV-23 is likely beneficial to immunocompromised adults by the Grading, Assessment, Development, and Evaluation (GRADE) framework, we conducted meta-analysis to examine its efficacy in an immunocompetent population. METHODS: We searched the PUBMED, EMBASE, and Cochrane Library databases for randomized trials. Overall relative risks (RRs) with 95% confidential intervals (CIs) were calculated, and the Cochrane Q test (p, I(2)) was performed. Outcomes were assessed by the GRADE framework. RESULTS: Seven randomized trials involving 156,010 participants were included in this meta analysis. High-quality evidence revealed that PPV-23 was weakly associated with the prevention of all-cause pneumonia ([RR] 0.87, [95%CI] 0.76-0.98, p=0.11, I(2)=43%), especially among the target population ([RR] 0.72, [95%CI] 0.69-0.94, p=0.58 I(2)=0%), the elderly group aged over 40 years ([RR] 0.80, [95%CI] 0.69 0.94) and the Japanese population ([RR] 0.72, [95%CI] 0.59-0.88, p=0.24, I(2)=30%). The target population included adults aged over 65 years and patients at high risk of pneumonia due to chronic lung disease, chronic obstructive pulmonary disease or living in a nursing home. Protective trends of PPV-23 in the outcomes of pneumococcal pneumonia ([RR] 0.54, [95%CI] 0.18-1.65, p=0.01, I(2)=77%) and mortality due to pneumonia ([RR] 0.67, [95%CI] 0.43-1.04, p=0.67, I(2)=0%) were observed, although the results were statistically insignificant, possibly due to the small number of trials included. PPV-23 did not prevent all cause mortality ([RR] 1.04, [95%CI] 0.87-1.24, p=0.95, I(2)=0%). CONCLUSIONS: PPV 23 provided weak protection against all-cause pneumonia in an immunocompetent population, especially among the target population. The additional benefit of PPV 23 in preventing CAP further supports its application in the target population. PMID- 26899377 TI - Impact and cost-effectiveness of a second tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine dose to prevent pertussis in the United States. AB - INTRODUCTION: The United States experienced a substantial increase in reported pertussis cases over the last decade. Since 2005, persons 11 years and older have been routinely recommended to receive a single dose of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine. The objective of this analysis was to evaluate the potential impact and cost-effectiveness of recommending a second dose of Tdap. METHODS: A static cohort model was used to calculate the epidemiologic and economic impact of adding a second dose of Tdap at age 16 or 21 years. Projected costs and outcomes were examined from a societal perspective over a 20-year period. Quality-adjusted Life Years (QALY) saved were calculated. RESULTS: Using baseline pertussis incidence from the National Notifiable Diseases Surveillance System, Tdap revaccination at either age 16 or 21 years would reduce outpatient visits by 433 (5%) and 285 (4%), and hospitalization cases by 7 (7%) and 5 (5%), respectively. The costs per QALY saved with a second dose of Tdap were approximately US $19.7 million (16 years) and $26.2 million (21 years). In sensitivity analyses, incidence most influenced the model; as incidence increased, the costs per QALY decreased. To a lesser degree, initial vaccine effectiveness and waning of effectiveness also affected cost outcomes. Multivariate sensitivity analyses showed that under a set of optimistic assumptions, the cost per QALY saved would be approximately $163,361 (16 years) and $204,556 (21 years). CONCLUSION: A second dose of Tdap resulted in a slight decrease in the number of cases and other outcomes, and that trend is more apparent when revaccinating at age 16 years than at age 21 years. Both revaccination strategies had high dollar per QALY saved even under optimistic assumptions in a multivariate sensitivity analysis. PMID- 26899378 TI - Visibility of Different Intraorbital Foreign Bodies Using Plain Radiography, Computed Tomography, Magnetic Resonance Imaging, and Cone-Beam Computed Tomography: An In Vitro Study. AB - PURPOSE: The study sought to compare the usefulness of 4 imaging modalities in visualizing various intraorbital foreign bodies (IOFBs) in different sizes. METHODS: Six different materials including metal, wood, plastic, stone, glass. and graphite were cut in cylindrical shapes in 4 sizes (dimensions: 0.5, 1, 2, and 3 mm) and placed intraorbitally in the extraocular space of fresh sheep's head. Four skilled radiologists rated the visibility of the objects individually using plain radiography, spiral computed tomography (CT), magnetic resonance imaging (MRI), and cone-beam computed tomography (CBCT) in accordance with a previously described grading system. RESULTS: Excluding wood, all embedded foreign bodies were best visualized in CT and CBCT images with almost equal accuracies. Wood could only be detected using MRI, and then only when fragments were more than 2 mm in size. There were 3 false-positive MRI reports, suggesting air bubbles as wood IOFBs. CONCLUSIONS: Because of lower cost and using less radiation in comparison with conventional CT, CBCT can be used as the initial imaging technique in cases with suspected IOFBs. Optimal imaging technique for wood IOFBs is yet to be defined. PMID- 26899379 TI - Enteric Distribution of Oral Contrast in Emergency Department Patients Undergoing Abdominal-Pelvic Computed Tomography. AB - PURPOSE: The study sought to assess the gastrointestinal (GI) distribution of oral contrast (OC) among emergency department (ED) patients and determine if contrast reaches the terminal ileum or site of pathology to assist in diagnosis. METHODS: Retrospectively, adults undergoing abdominal-pelvic computed tomography (APCT) in the ED at 2 hospitals were identified over a 3-month period. APCTs were reviewed for location of OC. Presence, site, type of bowel pathology, and prior gastrointestinal surgery were documented. When applicable, the site of bowel pathology was evaluated for the presence or absence of OC. RESULTS: There were 1349 exams with mean age 50.5 years (range 18-97 years), 41% male, with 530 (39%) receiving OC. In 271 of 530 (51%), OC reached the terminal ileum (TI). Bowel pathology was present in 31% of cases (165 of 530). When bowel pathology was present, 47% (77 of 165) had OC present at the pathology site. The GI tract was divided into 4 anatomic segments: OC most frequently reached pathology in stomach and duodenum (84%), but was present less frequently at sites of pathology from jejunum to TI (35%), proximal colon (57%), and distal colon (28%). In only 84 of 530 OC cases (16%) did contrast extend from the stomach to distal colon. OC administration contributed to longer mean APCT order to final report of 0.5 hours and longer mean ED length of stay of 0.8 hours compared with all patients who received APCT. CONCLUSIONS: Optimal OC distribution is not achieved in more than half of ED patients, raising questions about the continued use of OC in the ED. PMID- 26899381 TI - Forests and ozone: productivity, carbon storage, and feedbacks. AB - Tropospheric ozone is a serious air-pollutant, with large impacts on plant function. This study demonstrates that tropospheric ozone, although it damages plant metabolism, does not necessarily reduce ecosystem processes such as productivity or carbon sequestration because of diversity change and compensatory processes at the community scale ameliorate negative impacts at the individual level. This study assesses the impact of ozone on forest composition and ecosystem dynamics with an individual-based gap model that includes basic physiology as well as species-specific metabolic properties. Elevated tropospheric ozone leads to no reduction of forest productivity and carbon stock and to increased isoprene emissions, which result from enhanced dominance by isoprene-emitting species (which tolerate ozone stress better than non-emitters). This study suggests that tropospheric ozone may not diminish forest carbon sequestration capacity. This study also suggests that, because of the often positive relationship between isoprene emission and ozone formation, there is a positive feedback loop between forest communities and ozone, which further aggravates ozone pollution. PMID- 26899383 TI - Human skin-derived fibroblasts used as a 'Trojan horse' for drug delivery. AB - BACKGROUND: Drug toxicity currently represents the main challenge of tumour chemotherapy. Our group recently developed a new method for drug delivery inspired by the 'Trojan Horse' concept. Human mesenchymal stem cells (hMSCs) have been shown to play the role of new 'horses' in delivering anti-tumour agents, without involving any genetic manipulation. As human stromal dermal fibroblasts (hSDFs) represent an interesting alternative to hMSCs, being easy to isolate, they could be an ideal candidate for this kind of procedure. AIM: To investigate whether hSDFs can take up and deliver paclitaxel (PTX) in sufficient concentrations to inhibit a very aggressive melanoma tumour (IgR39) in vitro. METHODS: hSDFs were primed with high doses of PTX, and then the effect of drug delivery on IgR39 melanoma proliferation in vitro was evaluated using several assays (antiproliferation, transwell cocultures, rosette assays and colony growth assays). Furthermore, the cell cycle and PTX uptake/release mechanism of hSDFs were studied both under both normal and hypoxic conditions. RESULTS: hSDFs incorporated PTX and then released it with unaffected pharmacological activity, inhibiting human IgR39 melanoma growth in vitro. The hypoxic conditions did not induce changes in cell cycle pattern and the uptake-release mechanism with PTX was not affected. CONCLUSIONS: hSDFs can be used as a Trojan horse, as the released drug was functionally active. These results indicated that these cells could be used for clinical treatment as the drug was released into the cellular environment and the primed cells underwent apoptosis. PMID- 26899384 TI - Carotid Endarterectomy After Intravenous Thrombolysis: The Sooner the Better? PMID- 26899380 TI - The REGgamma-proteasome forms a regulatory circuit with IkappaBE and NFkappaB in experimental colitis. AB - Increasing incidence of inflammatory bowel disorders demands a better understanding of the molecular mechanisms underlying its multifactorial aetiology. Here we demonstrate that mice deficient for REGgamma, a proteasome activator, show significantly attenuated intestinal inflammation and colitis associated cancer in dextran sodium sulfate model. Bone marrow transplantation experiments suggest that REGgamma's function in non-haematopoietic cells primarily contributes to the phenotype. Elevated expression of REGgamma exacerbates local inflammation and promotes a reciprocal regulatory loop with NFkappaB involving ubiquitin-independent degradation of IkappaBE. Additional deletion of IkappaBE restored colitis phenotypes and inflammatory gene expression in REGgamma-deficient mice. In sum, this study identifies REGgamma-mediated control of IkappaBE as a molecular mechanism that contributes to NFkappaB activation and promotes bowel inflammation and associated tumour formation in response to chronic injury. PMID- 26899385 TI - A fluorescent aptasensor for sensitive analysis oxytetracycline based on silver nanoclusters. AB - A fluorescent aptasensor for detection of oxytetracycline (OTC) was presented based on fluorescence quenching of DNA aptamer-templated silver nanoclusters (AgNCs). The specific DNA scaffolds with two different nucleotides fragments were used: one was enriched with a cytosine sequence fragment (C12) that could produce DNA-AgNCs via a chemical reduction method, and another was the OTC aptamer fragment that could selectively bind to the OTC antibiotic. Thus, the as-prepared AgNCs could exhibit quenched fluorescence after binding to the target OTC. The fluorescence ratio of the DNA-AgNCs was quenched in a linearly proportional manner to the concentration of the target in the range of 0.5 nM to 100 nM with a detection limit of 0.1 nM. This proposed nanobiosensor was demonstrated to be sensitive, selective, and simple, introducing a viable alternative for rapid determination of toxin OTC in honey and water samples. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26899386 TI - The role of microfibrillar-associated protein 4 (MFAP4) in the formation and function of splenic compartments during embryonic and adult life. AB - Microfibrillar-associated protein 4 (MFAP4) is an extracellular protein belonging to the fibrinogen-related protein superfamily and is recognized as an integrin ligand with suggested functions in pulmonary and vascular tissue homeostasis. MFAP4 expression in the spleen is increased during infections; however, the significance of MFAP4 for the function of the spleen is unknown. Immunohistochemistry, morphometry and real-time RT-PCR were used to analyze wild type and MFAP4-deficient spleens. In addition, they were compared with splenic tissue, which was newly formed 8 weeks after avascular implantation into adult mice in order to obtain information about the role of MFAP4 in the formation of splenic tissue during ontogeny and adult life. The present study shows that MFAP4 is co-localized with laminin in the B- and T-cell zones of the spleen, in addition to capsular and trabecular expression. MFAP4 is most likely produced by fibroblastic reticulum cells and follicular dendritic cells of the spleen but can also be imported via the blood from other tissues. The development of splenic tissue is not disturbed in MFAP4-deficient mice. However, in splenic tissue regenerating under MFAP4-deficient conditions, the number of FDCs is significantly decreased but is corrected by MFAP4 imported from other tissues. No differences were observed for lymphocyte numbers or splenic structure. The data indicate that MFAP4 promotes FDC development in regenerating splenic tissue and warrant further investigations regarding the MFAP4 dependency of splenic B-cell maturation. PMID- 26899387 TI - Impact of preoperative Vitamin D3 administration on postoperative hypocalcaemia in patients undergoing total thyroidectomy (HypoCalViD): study protocol for a randomized controlled trial. AB - BACKGROUND: Total thyroidectomy is increasingly used as a surgical approach for many thyroid conditions. Subsequently, postoperative hypocalcaemia is observed with increasing frequency, often resulting in prolonged hospital stay, increased use of resources, reduced quality of life and delayed return to work. The administration of vitamin D is essential in the therapy of postoperative hypocalcaemia; calcitriol is most commonly used. What has not been examined so far is whether and how routine preoperative vitamin D prophylaxis using calcitriol can help to prevent postoperative hypocalcaemia. This study evaluates routine preoperative calcitriol prophylaxis for all patients who are to undergo a total thyroidectomy, compared with the current standard of post-treatment, i.e., selective vitamin D treatment for patients with postoperative hypocalcaemia. METHODS/DESIGN: This clinical observational (minimal interventional clinical trial) trial is a multicentre, prospective, randomized superiority trial with an adaptive design. Datasets will be pseudonymized for analysis. Patients will be randomly allocated (1:1) to the intervention and the control groups. The only intervention is 0.5 MUg calcitriol orally twice a day for 3 days prior to surgery. For the primary endpoint measure (number of patients with hypocalcaemia), hypocalcaemia is defined as serum calcium of less than 2.1 mmol/l on any day during the postoperative course; this measure will be analyzed using a Chi-square test comparing the two groups. Secondary endpoint measures, such as number of days to discharge, quality of life, and economic parameters will also be analyzed. DISCUSSION: By virtue of the direct comparison of clinically and economically relevant endpoints, the efficacy as well as efficiency of preoperative calcitriol prophylaxis of hypocalcaemia will be clarified. These results should be available 24 months after the first patient has been enrolled. The results will be used to inform a revised practice parameter guideline of whether or not to recommend preoperative calcitriol for all patients in whom total thyroidectomy is planned. TRIAL REGISTRATION: Deutsches Register Klinischer Studien, DRKS00005615 (Feb.12.2016). PMID- 26899389 TI - Is SEEG safe? A systematic review and meta-analysis of stereo electroencephalography-related complications. AB - OBJECTIVE: Stereo-electroencephalography (SEEG) is a procedure performed for patients with intractable epilepsy in order to anatomically define the epileptogenic zone (EZ) and the possible related functional cortical areas. By avoiding the need for large craniotomies and due to its intrinsic precision placement features, SEEG may be associated with fewer complications. Nevertheless, intracerebral electrodes have gained a reputation of excessive invasiveness, with a "relatively high morbidity" associated with their placement. A systematic literature review and meta-analysis of SEEG complications has not been previously performed. The goal of this study is to quantitatively review the incidence of various surgical complications associated with SEEG electrode implantation in the literature and to provide a summary estimate. This will allow physicians to accurately counsel their patients about the potential complications related to this method of extraoperative invasive monitoring. METHODS: The systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We conducted MEDLINE, Scopus, and Web of Science database searches with the search algorithm. We analyzed complication rates using a fixed-effects model with inverse variance weighting. Calculations for the meta-analysis and construction of forest plots were completed using an established spreadsheet. The principal summary measures were the effect summary value and 95% confidence intervals (CIs). RESULTS: The initial 1,901 retrieved citations were reviewed. After removing 787 duplicates, the titles and abstracts of 1,114 publications were screened. At this stage, studies that did not mention the absence or presence of complications following SEEG or that did not fulfill the inclusion criteria in any manner were excluded. After excluding 1,057 citations, the full text was assessed in the resulting 57 articles for eligibility criteria. The most common complications were hemorrhagic (pooled prevalence 1.0%, 95% confidence interval [CI] 0.6-1.4%) or infectious (pooled prevalence 0.8%, 95% CI 0.3-1.2%). Five mortalities were identified (pooled prevalence 0.3%, 95% CI -0.1-0.6%). Overall, our analysis identified 121 surgical complications related to SEEG insertion and monitoring (pooled prevalence 1.3%, 95% CI 0.9-1.7%). SIGNIFICANCE: This review represents a comprehensive estimation of the actual incidence of complications related to SEEG. We report a rate substantially lower than the complication rates reported for other methods of extraoperative invasive monitoring. These data should alleviate the concerns of some regarding the safety of the "stereotactic" method, allowing a better decision process among the different methods of invasive monitoring and ameliorating the fear associated with the placement of depth electrodes. PMID- 26899388 TI - A beneficial tumor microenvironment in oropharyngeal squamous cell carcinoma is characterized by a high T cell and low IL-17(+) cell frequency. AB - Patients with HPV-positive oropharyngeal squamous cell carcinomas (OPSCCs) have a better prognosis than patients with non-HPV-induced OPSCC. The role of the immune response in this phenomenon is yet unclear. We studied the number of T cells, regulatory T cells (Tregs), T helper 17 (Th17) cells and IL-17(+) non-T cells (mainly granulocytes) in matched HPV-positive and HPV-negative OPSCC cases (n = 162). Furthermore, the production of IFN-gamma and IL-17 by tumor-infiltrating T cells was analyzed. The number of tumor-infiltrating T cells and Tregs was higher in HPV-positive than HPV-negative OPSCC (p < 0.0001). In contrast, HPV-negative OPSCC contained significantly higher numbers of IL-17(+) non-T cells (p < 0.0001). Although a high number of intra-tumoral T cells showed a trend toward improved survival of all OPSCC patients, their prognostic effect in patients with a low number of intra-tumoral IL-17(+) non-T cells was significant with regard to disease-specific (p = 0.033) and disease-free survival (p = 0.012). This suggests that a high frequency of IL-17(+) non-T cells was related to a poor immune response, which was further supported by the observation that a high number of T cells was correlated with improved disease-free survival in the HPV-positive OPSCC (p = 0.008). In addition, we detected a minor Th17 cell population. However, T cells obtained from HPV-positive OPSCC produced significantly more IL 17 than those from HPV-negative tumors (p = 0.006). The improved prognosis of HPV positive OPSCC is thus correlated with higher numbers of tumor-infiltrating T cells, more active Th17 cells and lower numbers of IL-17(+) non-T cells. PMID- 26899391 TI - Prolonging life at all costs: quantity versus quality. PMID- 26899392 TI - Another STEP forward in emphysema treatment. PMID- 26899390 TI - Segmental volume reduction using thermal vapour ablation in patients with severe emphysema: 6-month results of the multicentre, parallel-group, open-label, randomised controlled STEP-UP trial. AB - BACKGROUND: Lung volume reduction of emphysematous lobes results in clinical improvement for patients with severe emphysema. However, some segments within a lobe are often substantially more diseased than others, thereby warranting a more targeted approach of the emphysematous parts of a lobe. We therefore did a study to assess whether or not selective sequential treatment of the more diseased upper lobe segments with bronchoscopic vapour ablation led to clinical improvement. METHODS: For the multicentre, parallel-group, randomised, controlled, open-label Sequential Staged Treatment of Emphysema with Upper Lobe Predominance (STEP-UP) trial, adult patients aged 45-75 years with severe, upper lobe-predominant emphysema with a forced expiratory volume in 1 s (FEV1) between 20% and 45%, substantial hyperinflation, and post-rehabilitation 6-min walk test (6MWT) greater than 140 m were enrolled from 13 hospital sites in Europe (ten sites) and Australia (three sites). A computer-generated blocked randomisation scheme (block size three per site based on a random table from an independent biostatistician) stratified by site was used to randomly assign enrolled patients 2:1 to segmental vapour ablation (treatment group) or standard medical management (control group). Patients and investigators were not masked to group assignment. The primary efficacy endpoints were statistically significant changes in FEV1 and St George's Respiratory Questionnaire (SGRQ-C) scores between trial groups at 6 months, analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01719263. FINDINGS: Between June 30, 2013, and Oct 1, 2014, 134 patients were screened and 70 were enrolled and randomly assigned: 46 to the treatment group and 24 to the control group. One patient in the treatment group did not receive treatment because of physician decision post randomisation; this patient is excluded from all analyses. The mean relative improvement in FEV1 between the treatment group versus the control group was 14.7% (95% CI 7.8-21.5%; p<0.0001) and in SGRQ-C was -9.7 points (95% CI -15.7 to -3.7; p=0.0021). COPD exacerbation was the most common serious adverse event, occurring in 11 (24%) of 45 patients in the treatment group and one (4%) of 24 in the control group. One exacerbation resulted in a patient death 84 days after treatment; this was judged by the data and safety monitoring board to be possibly related to treatment. No pneumothorax occurred within 30 days of treatment. INTERPRETATION: Compared with standard medical management, targeted thermal vapour ablation of more diseased segments and preservation of less diseased segments resulted in clinically meaningful and statistically significant improvements in lung function and quality of life at 6 months, with an acceptable safety profile. FUNDING: Uptake Medical. PMID- 26899393 TI - iPSCs Derived from Malignant Tumor Cells: Potential Application for Cancer Research. AB - The development of induced pluripotent stem cell (iPSC) technology has inspired a series of methods to manipulate cell fate and has provided novel insight into the profound molecular events underlying the development of diseases. Reprogramming somatic cells into iPSCs has been intensively investigated. However, few studies have investigated the reprogramming of malignant cells and its potential application. Herein, we review the recent progress of iPSCs derived from malignant cells, and highlight tumor iPSCs applications on cancer research which mainly focus on mesenchymal-epithelial transition, genetic and epigenetic change, diseases model construction, drug screening and tumor pathway study. PMID- 26899394 TI - Germline Stem Cells: A Useful Tool for Therapeutic Cloning. AB - BACKGROUND: Numerous articles have been published on the potential of using embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in clinical applications. As these types of stem cell are well studied, the research on germline stem cells (GSCs), which hold a huge potential for clinical application and permanent treatment for infertility, is left behind. Besides possessing the characteristics of being able to self-renew and to give rise to differentiated progeny throughout postnatal life, the potential of GSCs to transform into pluripotent status is remarkable but is unexploited. OBJECTIVE: To explore the potential of germline stem cells in therapeutic usage, it's required to understand the underlying transformation mechanism of germline stem cells into pluripotent cells. RESULTS: In this review, we summarized development of ESCs, GSCs, iPSCs, and embryonic stem-like (ES-like) cells derived from GSCs, discussed feasibility and the technical hurdles of using these types of stem cells in therapeutic cloning, and finally focused on the comparison of the ESCs, iPSCs and ESlike cells in current as well as potential applications in medicine. Moreover, the prospects of female germline stem cells (FGSCs) and their derived ES-like cells were also discussed as a novel alternative in clinical application. CONCLUSION: With the capacity of germline reconstitution and transformation into pluripotent status, GSCs possess significant potential for clinic usage and therapeutic cloning. PMID- 26899395 TI - Template-Mediated Biomineralization for Bone Tissue Engineering. AB - Template-mediated mineralization describes a research field of materials chemistry that deals with templates influencing product formation of foremost inorganic functional materials and composites. These templates are usually organic compounds - as far as molecules with natural origin are involved, the terminology "biomineralization" or "biomimetic mineralization: is used. The present review gives insight into recent developments in the research area of bone-tissue engineering with focus on chemical templates and cell-based approaches. The review is structured as follows: (1) a brief general overview about the principle of templating and recently used template materials, (2) important analytical methods, (3) examples of template-guided mineralization of various bone-related materials, (4) natural bone mineralization, (5) scaffolds for bone-tissue regeneration and (6) cell-based therapeutic approaches. For this purpose, a literature screening with emphasis on promising potential practical applications was performed. In particular, macromolecular structures and polymer composites with relation to naturally occurring compounds were favored. Priority was given to publications of the last five years. Although the present review does not cover the whole topic to full extent, it should provide information about current trends and the most promising approaches in the research area of bone-tissue engineering based on applications of organic templates/scaffolds as well as cell-based strategies. PMID- 26899396 TI - A review of the three-dimensional cell culture technique: Approaches, advantages and applications. AB - Cell culture is a core and basic technique in biotechnology and is widely applied in biology, medicine, drug research and development. Traditional two-dimensional cell culture methods have undergone great developments. However, with in-depth basic research, higher requirements are needed to better mimic the in vivo environment to accurately observe cell behavior and explore its mechanisms. To comply with this situation, the three-dimensional cell culture technique emerged and has made profound advances in sustaining inherent cell properties. Here, we briefly review the development of this technique, including the main approaches to form three-dimensional microtissues, and its application and potential for future clinical therapies. PMID- 26899398 TI - Prenatal smoking exposure, measured as maternal serum cotinine, and children's motor developmental milestones and motor function: A follow-up study. AB - BACKGROUND: Cohort studies have indicated an association between prenatal smoking exposure and children's motor difficulties. However, results are inconsistent and exposure is most often self-reported. Studies indicate that measurement of serum cotinine can result in a more accurate status of smoking exposure in comparison with self-report. OBJECTIVES: To investigate whether prenatal smoking exposure, measured as maternal serum cotinine, is associated with maternal interview based assessment of motor development in infancy (age at crawling, standing-up and walking) and motor skills at young school age (assessed by the Developmental Coordination Disorder Questionnaire 2007 (DCDQ'07)). METHOD: In 2002-2004, 1,253 pregnant women from Greenland and Ukraine were included in the INUENDO birth cohort. The participating women filled in questionnaires and 1,177 provided blood samples, which were analyzed for serum cotinine. Smokers were defined as women with a serum cotinine concentration >10ng/ml. At follow-up when the offspring were 6-9 years of age 1,026 of the parents from the cohort participated. They completed an interview-based questionnaire including questions about age at motor milestones of their children. In addition, child motor development was assessed using the questionnaire "DCDQ'07". Linear regression analyzes were performed and adjusted for covariates; age of the mother and child, parity, sex, maternal educational level, maternal pre-pregnancy alcohol consumption and duration of breastfeeding. Data were stratified by country. RESULTS: No statistically significant difference in age at motor milestones was found comparing children of smokers with children of non-smokers. Also, there was no statistically significant difference in motor score (Developmental Coordination Disorder Questionnaire Score, DCDQ-score) among five to seven-year-old children. However, in Greenland children of smokers had a lower DCDQ-score than children of non smokers at eight to nine years (-2.2 DCDQ points, 95% CI: -4.3;-0.1). Supplementary results for the same age group in Greenland showed that children of smokers had higher odds of being classified with motor difficulties in comparison with children of non-smokers (OR=1.9, 95% CI: 1.1;3.3). CONCLUSION: Maternal serum cotinine was not related to delayed motor development milestones or reduced motor function abilities in children up to 7 years of age. Reduced motor skills observed in 8-9 years old exposed children warrant further study. PMID- 26899399 TI - Tailoring through Technology: A Retrospective Review of a Single Surgeon's Experience with Implant-Based Breast Reconstruction before and after Implementation of Laser-Assisted Indocyanine Green Angiography. AB - Reported complication rates of implant-based breast reconstruction in the literature exceed 50%, with mastectomy skin flap necrosis reported to occur in up to 25% of cases. Laser-assisted indocyanine green angiography (LA-ICGA) technology allows the surgeon to optimize preservation of the mastectomy skin flap while avoiding skin necrosis. The purpose of this study was to determine if outcomes of breast reconstruction are beneficially affected by using LA-ICGA. A total 269 consecutive women (467 breast reconstructions) undergoing implant-based breast reconstruction from 2008 to 2013 were examined. The complication rates of those who underwent reconstruction prior to the implementation of LA-ICGA were compared with those who were reconstructed after implementation of LA-ICGA. A total of 254 consecutive breast reconstructions were performed prior to implementation of LA-ICGA, and 213 breasts were reconstructed with the use of LA ICGA. After implementation of LA-ICGA System, the rate of mastectomy skin flap necrosis decreased by 86% (6.7% versus 0.9%, p = 0.02). The overall complication rate prior to LA-ICGA was 13.8% compared with 6.6% with the use of LA-ICGA (p = 0.01). After LA-ICGA was incorporated, the percentage of patients undergoing single-stage reconstruction increased from 12% to 32% (p = <0.001). Implementation of LA-ICGA provides the surgeon with an objective assessment of mastectomy flap perfusion resulting in a trend toward overall reduction in complications as well as an 86% decrease in the rate of subsequent skin necrosis. The objective assessment of mastectomy flap perfusion allows the surgeon to tailor breast reconstruction intraoperatively, in real-time, adjusting for the individual patient's mastectomy flap perfusion. PMID- 26899400 TI - Analysis of prescription patterns in opioid deaths shows startling findings: Re: Lev R, Lee O, Petro S, Lucas J, Castillo EM, Vilke GM, Coyne CJ. Who is prescribing controlled medications to patients who die of prescription drug abuse? Am J Emerg Med. 2016 Jan.;34(1):30-5. PMID- 26899397 TI - Toluene inhalation exposure for 13 weeks causes persistent changes in electroretinograms of Long-Evans rats. AB - Studies of humans chronically exposed to volatile organic solvents have reported impaired visual functions, including low contrast sensitivity and reduced color discrimination. These reports, however, lacked confirmation from controlled laboratory experiments. To address this question experimentally, we examined visual function by recording visual evoked potentials (VEP) and/or electroretinograms (ERG) from four sets of rats exposed repeatedly to toluene. In addition, eyes of the rats were examined with an ophthalmoscope and some of the retinal tissues were evaluated for rod and M-cone photoreceptor immunohistochemistry. The first study examined rats following exposure to 0, 10, 100 or 1000ppm toluene by inhalation (6hr/d, 5d/wk) for 13 weeks. One week after the termination of exposure, the rats were implanted with chronically indwelling electrodes and the following week pattern-elicited VEPs were recorded. VEP amplitudes were not significantly changed by toluene exposure. Four to five weeks after completion of exposure, rats were dark-adapted overnight, anesthetized, and several sets of electroretinograms (ERG) were recorded. In dark-adapted ERGs recorded over a 5-log (cd-s/m(2)) range of flash luminance, b-wave amplitudes were significantly reduced at high stimulus luminance values in rats previously exposed to 1000ppm toluene. A second set of rats, exposed concurrently with the first set, was tested approximately one year after the termination of 13 weeks of exposure to toluene. Again, dark-adapted ERG b-wave amplitudes were reduced at high stimulus luminance values in rats previously exposed to 1000ppm toluene. A third set of rats was exposed to the same concentrations of toluene for only 4 weeks, and a fourth set of rats exposed to 0 or 1000ppm toluene for 4 weeks were tested approximately 1year after the completion of exposure. No statistically significant reductions of ERG b-wave amplitude were observed in either set of rats exposed for 4 weeks. No significant changes were observed in ERG a-wave amplitude or latency, b-wave latency, UV- or green-flicker ERGs, or in photopic flash ERGs. There were no changes in the density of rod or M-cone photoreceptors. The ERG b-wave reflects the firing patterns of on-bipolar cells. The reductions of b-wave amplitude after 13 weeks of exposure and persisting for 1year suggest that alterations may have occurred in the inner nuclear layer of the retina, where the bipolar cells reside, or the outer or inner plexiform layers where the bipolar cells make synaptic connections. These data provide experimental evidence that repeated exposure to toluene may lead to subtle persistent changes in visual function. The fact that toluene affected ERGs, but not VEPs, suggests that elements in the rat retina may be more sensitive to organic solvent exposure than the rat visual cortex. PMID- 26899401 TI - Electrospun Contrast-Agent-Loaded Fibers for Colon-Targeted MRI. AB - Magnetic resonance imaging is a diagnostic tool used for detecting abnormal organs and tissues, often using Gd(III) complexes as contrast-enhancing agents. In this work, core-shell polymer fibers have been prepared using coaxial electrospinning, with the intent of delivering gadolinium (III) diethylenetriaminepentaacetate hydrate (Gd(DTPA)) selectively to the colon. The fibers comprise a poly(ethylene oxide) (PEO) core loaded with Gd(DTPA), and a Eudragit S100 shell. They are homogeneous, with distinct core-shell phases. The components in the fibers are dispersed in an amorphous fashion. The proton relaxivities of Gd(DTPA) are preserved after electrospinning. To permit easy visualization of the release of the active ingredient from the fibers, analogous materials are prepared loaded with the dye rhodamine B. Very little release is seen in a pH 1.0 buffer, while sustained release is seen at pH 7.4. The fibers thus have the potential to selectively deliver Gd(DTPA) to the colon. Mucoadhesion studies reveal there are strong adhesive forces between porcine colon mucosa and PEO from the core, and the dye-loaded fibers can be successfully used to image the porcine colon wall. The electrospun core-shell fibers prepared in this work can thus be developed as advanced functional materials for effective imaging of colonic abnormalities. PMID- 26899402 TI - Inflammatory breast cancer: A decade of experience. AB - Inflammatory breast cancer (IBC) is an aggressive and rare form of breast cancer. At present, there are no established diagnostic, radiological, pathological or molecular diagnostic criteria for this entity. The aim of this study was to examine the patterns of presentation, treatment and outcomes of IBC in this institution over the course of a decade. This is a retrospective observational study using data from the Royal Perth Hospital from January 2001 to December 2010. Our results identified 57 women with IBC, representing 1.9% of all new breast cancer presentations. Human Epidermal Growth Factor Receptor 2 (HER2) positive and triple negative tumors were overrepresented (41% and 18%, respectively). Forty-four (77%) patients had early disease at diagnosis, of whom 35 underwent surgery and 16 are relapse-free. All six patients achieving complete pathological response were relapse-free in contrast to 11 (38%) with lesser responses at a median follow-up of 59 months. Median survival in 13 patients with metastatic disease at diagnosis was 21.7 months, with two patients still in remission. Clearly, this small but important group continues to offer management challenges and warrants ongoing study, including better molecular and pathological profiling of tumors to allow improved diagnostic clarity and more effective targeted therapy. PMID- 26899403 TI - Experimental myocardial stem cell therapy for ST-elevation myocardial infarction: rationale and level of evidence. AB - Ischemic heart disease (IHD) is one of the leading causes of death worldwide and is characterized by the formation of atherosclerotic plaques in the coronary arteries reducing the blood supply to the heart muscle causing ischemia. IHD can result in ST-elevation myocardial infarction (STEMI), chronic IHD and heart failure. The patients suffer from chest pain (angina), dyspnea and a reduced quality of life. Common for all these conditions is loss of functional cardiomyocytes and endothelial cells. Stem cell therapy to regenerate injured myocardium is a new treatment option which has gained much interest in the last 10-15 years especially after STEMI. Many preclinical and clinical studies have shown encouraging results but also very diverse clinical outcomes after stem cell treatment. This diversity in results may be explained by different factors, such as cell isolation technique, infarct location, timing and route of delivery, cell dosage, cell type etc. The present review will try to elaborate and clarify the present status for stem cell therapy in STEMI. PMID- 26899405 TI - Similarity of different lifting techniques in trunk muscular synergies. AB - Lifting is known to be a major reason for musculoskeletal injuries. In this way, lifting has a crucial effect on human musculoskeletal system and intensity of this impact depends slightly on the selection of techniques. Underlying mechanisms by which trunk muscles are executed during performing lifting are central to biomechanical study of lifting techniques. In the current study, the trunk muscular control mechanisms of lifting are investigated using the synergetic control analysis. Non-negative matrix factorization has been used to extract trunk muscles synergies from their activities - which are computed by a previously validated musculoskeletal model - during different lifting techniques aimed to investigate motor control strategies. Three lifting techniques are considered; stoop, squat and semi-squat. Three synergies account for variety among muscle activation of trunk muscles with related VAF (Variability Account For) of over 95%. Trunk muscle synergy weightings and related time-varying coefficients are calculated for each kind of lifting techniques considering three synergies. Paired correlation coefficients between muscle synergies are all greater than 0.91 (P < 0.05) suggesting that trunk muscle synergies are similar for examined techniques in spite of their kinematic diversity. This similarity can be a result of their common ultimate goal. The acquired results also elucidate the mechanisms of muscle activation patterns that can be exploited in future studies and ergonomic interventions. PMID- 26899406 TI - Response Surface Analysis and Nonlinear Optimization Algorithm for Maximization of Clinical Drug Performance: Application to Extended-Release and Long-Acting Injectable Paliperidone. AB - Model-based approach is recognized as a tool to make drug development more productive and to better support regulatory and therapeutic decisions. The objective of this study was to develop a novel model-based methodology based on the response surface analysis and a nonlinear optimizer algorithm to maximize the clinical performances of drug treatments. The treatment response was described using a drug-disease model accounting for multiple components such as the dosage regimen, the pharmacokinetic characteristics of a drug (including the mechanism and the rate of drug delivery), and the exposure-response relationship. Then, the clinical benefit of a treatment was defined as a function of the diseases and the clinical endpoints and was estimated as a function of the target pharmacodynamic endpoints used to evaluate the treatment effect. A case study is presented to illustrate how the treatment performances of paliperidone extended release (ER) and paliperidone long-acting injectable (LAI) can be improved. A convolution based approach was used to characterize the pharmacokinetics of ER and LAI paliperidone. The drug delivery properties and the dosage regimen maximizing the clinical benefit (defined as the target level of D2 receptor occupancy) were estimated using a nonlinear optimizer. The results of the analysis indicated that a substantial improvement in clinical benefit (from 15% to 27% for the optimization of the in vivo release and from ~30% to ~70% for the optimization of dosage regimen) was obtained when optimal strategies were deployed either for optimizing the in vivo drug delivery properties of ER formulations or for optimizing the dosage regimen of LAI formulations. PMID- 26899404 TI - ER stress and the decline and fall of pancreatic beta cells in type 1 diabetes. AB - Components of the unfolded protein response (UPR) modulate beta cell inflammation and death in early type 1 diabetes (T1D). The UPR is a mechanism by which cells react to the accumulation of misfolded proteins in the endoplasmic reticulum (ER). It aims to restore cellular homeostasis, but in case of chronic or overwhelming ER stress the persistent activation of the UPR triggers apoptosis, contributing to the loss of beta cells in both T1D and type 2 diabetes. It remains to be determined how and why the transition from 'physiological' to 'pathological' UPR takes place. A key component of the UPR is the ER transmembrane protein IRE1alpha (inositol-requiring enzyme 1alpha). IRE1alpha activity is modulated by both intra-ER signals and by the formation of protein complexes at its cytosolic domain. The amplitude and duration of IRE1alpha signaling is critical for the transition between the adaptive and cell death programs, with particular relevance for the activation of the pro-apoptotic c-Jun N-terminal kinase (JNK) in beta cells. In the present review we discuss the available information on IRE1alpha-regulating proteins in beta cells and their downstream targets, and the important differences observed between cytokine induced UPR in human and rodent beta cells. PMID- 26899408 TI - Identification of Novel BACE1 Inhibitors by Combination of Pharmacophore Modeling, Structure-Based Design and In Vitro Assay. AB - The protease beta-secretase plays a critical role in the synthesis of pathogenic amyloid-beta in Alzheimer's disease. In this study, pharmacophore constructed from receptor-ligand complex was used to screen Chemdiv and Zinc database and the resulting hits were subjected to docking experiments using LiandFit and CDOCKER programs. Molecules with high consensus scores and good interaction patterns in docking programs were retained. Drug-likeness assay including Lipinski's rule of five and ADMET properties filters were further used to identify BACE1 inhibitor. Finally, 13 compounds with novel scaffolds were selected and, considering of the nature of relative high LogP value of many marketed AD drugs, three of them with top 3 predicted LogP value were evaluated for their IC50 values in vitro by BACE1 enzymatic activity study. We believe that compound 13 with an IC50 value of 136 uM can be a lead compound with great potential in BACE1 inhibition and increasing activity by subsequently structure modification or optimization. At the same time, we found that the interaction between the residues Asp228, Asp32 of BACE1 and ligands is significant through analyzing the binding mode of 13 candidate compounds. PMID- 26899409 TI - Sequential protein unfolding through a carbon nanotube pore. AB - An assortment of biological processes, like protein degradation and the transport of proteins across membranes, depend on protein unfolding events mediated by nanopore interfaces. In this work, we exploit fully atomistic simulations of an artificial, CNT-based nanopore to investigate the nature of ubiquitin unfolding. With one end of the protein subjected to an external force, we observe non canonical unfolding behaviour as ubiquitin is pulled through the pore opening. Secondary structural elements are sequentially detached from the protein and threaded into the nanotube, interestingly, the remaining part maintains native like characteristics. The constraints of the nanopore interface thus facilitate the formation of stable "unfoldon" motifs above the nanotube aperture that can exist in the absence of specific native contacts with the other secondary structure. Destruction of these unfoldons gives rise to distinct force peaks in our simulations, providing us with a sensitive probe for studying the kinetics of serial unfolding events. Our detailed analysis of nanopore-mediated protein unfolding events not only provides insight into how related processes might proceed in the cell, but also serves to deepen our understanding of structural arrangements which form the basis for protein conformational stability. PMID- 26899410 TI - Usefulness of AFD concept: limitations to overcome. PMID- 26899411 TI - Patch formation of a viral channel forming protein within a lipid membrane--Vpu of HIV-1. AB - Ion channels and their viral companions are defined by their quaternary structure. The individual sub-units have to assemble into homo- or hetero oligomers. Using Vpu of HIV-1, a putative viral channel forming protein (VCP), as a test case, the formation of a quaternary structure is monitored using coarse grained molecular dynamics (CGMD) simulations. Full length Vpu is generated by combining the helical transmembrane domain (TMD) with the cytoplasmic domain derived from NMR spectroscopy. Patches of 2 to 6 as well as patches of 16 and 32 Vpu proteins, Vpu-WT, containing unphosphorylated serines 52 and 56 are used to study assembly dynamics. The same patches are simulated for the Vpu double mutant, Vpu-DD, in which the two serines 52 and 56 are replaced by aspartic acid. Serines 52 and 56 in Vpu-WT allow short lived contacts between the cytoplasmic domains. Dimer formation is the first step for long lasting assemblies and is induced by the EYR motif. Roll-over movements allow rearrangement within the dimer. Independent of the number of Vpu proteins, Vpu-DD prefers smaller aggregates than Vpu-WT. In the case of simulation of 4 Vpu-WT proteins a pore like assembly is directly identified with the TMD Ser-23 pointing towards a putative central pore axis. PMID- 26899412 TI - Re: The challenge of Clostridium difficile infection: Overview of clinical manifestations, diagnostic tools and therapeutic options. PMID- 26899413 TI - Clinical characteristics and antimicrobial patterns in complicated intra abdominal infections: a 6-year epidemiological study in southern China. AB - Complicated intra-abdominal infection (cIAIs) are a common and important cause of morbidity worldwide. In this study, the clinical features, microbiological profiles, antimicrobial patterns and treatments of 3233 cIAI patients (mean age, 47.6 years; 54.7% male) with 3531 hospitalisations from 2008-2013 were retrospectively investigated. The most commonly isolated bacteria were Escherichia coli (47.6%), Klebsiella pneumoniae (16.9%), Enterococcus faecalis (10.4%) and Pseudomonas aeruginosa (8.8%). Ciprofloxacin, aminoglycoside (gentamicin), piperacillin/tazobactam and carbapenems exhibited activity against 53%, 76%, 88% and 100% of extended-spectrum beta-lactamase (ESBL)-positive Enterobacteriaceae isolates, respectively. Pseudomonas aeruginosa isolates exhibited 100%, 95%, 88%, 71% and 76% susceptibility to aminoglycoside (gentamicin), ciprofloxacin, meropenem, imipenem and ceftazidime, respectively, and Enterococcus remained 100% susceptible to vancomycin and linezolid. beta Lactam antibacterials other than penicillin (specifically third-generation cephalosporins) and imidazole derivatives (ornidazole and metronidazole) were the most common first-line treatments. Patients subjected to regimen change after initial antibiotic treatment had predisposing conditions (e.g. older age, more severe co-morbidities) and a higher incidence of P. aeruginosa infection; in addition, these patients encountered a higher average cost of care and worse clinical outcomes compared with those without medication modification. Taken together, these findings indicate the importance of appropriate initial empirical therapy and suggest the use of combination therapy comprising cephalosporins and metronidazole. PMID- 26899414 TI - Detection of translocatable units in a blaCTX-M-15 extended-spectrum beta lactamase-producing ST131 Escherichia coli isolate using a hybrid sequencing approach. PMID- 26899416 TI - Synthesis of molecularly imprinted polymer nanoparticles for the fast and highly selective adsorption of sunset yellow. AB - Novel molecularly imprinted polymer nanoparticles were synthesized by precipitation polymerization with sunset yellow as the template and [2 (methacryloyloxy)ethyl] trimethylammonium chloride as the functional monomer. The molecularly imprinted polymer nanoparticles were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, and their specific surface area and thermal stability were measured. The molecularly imprinted polymer nanoparticles had a high adsorption capacity in wide pH range (pH 1-8) for sunset yellow. The adsorption equilibrium only needed 5 min, and the quantitative desorption was very fast (1 min) by using 10.0 mol/L HCl as the eluant. The maximum adsorption capacity of the molecularly imprinted polymer nanoparticles for sunset yellow was 144.6 mg/g. The adsorption isotherm and kinetic were well consistent with Langmuir adsorption model and pseudo-second-order kinetic model, respectively. The relative selectivity coefficients of the molecularly imprinted polymer nanoparticles for tartrazine and carmine were 9.766 and 12.64, respectively. The prepared molecularly imprinted polymer nanoparticles were repeatedly used and regenerated ten times without significant absorption capacity decrease. PMID- 26899415 TI - Anaesthesia for hip fracture surgery in adults. AB - BACKGROUND: The majority of people with hip fracture are treated surgically, requiring anaesthesia. OBJECTIVES: The main focus of this review is the comparison of regional versus general anaesthesia for hip (proximal femoral) fracture repair in adults. We did not consider supplementary regional blocks in this review as they have been studied in another review. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library; 2014, Issue 3), MEDLINE (Ovid SP, 2003 to March 2014) and EMBASE (Ovid SP, 2003 to March 2014). SELECTION CRITERIA: We included randomized trials comparing different methods of anaesthesia for hip fracture surgery in adults. The primary focus of this review was the comparison of regional anaesthesia versus general anaesthesia. The use of nerve blocks preoperatively or in conjunction with general anaesthesia is evaluated in another review. The main outcomes were mortality, pneumonia, myocardial infarction, cerebrovascular accident, acute confusional state, deep vein thrombosis and return of patient to their own home. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. We analysed data with fixed-effect (I(2) < 25%) or random-effects models. We assessed the quality of the evidence according to the criteria developed by the GRADE working group. MAIN RESULTS: In total, we included 31 studies (with 3231 participants) in our review. Of those 31 studies, 28 (2976 participants) provided data for the meta-analyses. For the 28 studies, 24 were used for the comparison of neuraxial block versus general anaesthesia. Based on 11 studies that included 2152 participants, we did not find a difference between the two anaesthetic techniques for mortality at one month: risk ratio (RR) 0.78, 95% confidence interval (CI) 0.57 to 1.06; I(2) = 24% (fixed-effect model). Based on six studies that included 761 participants, we did not find a difference in the risk of pneumonia: RR 0.77, 95% CI 0.45 to 1.31; I(2) = 0%. Based on four studies that included 559 participants, we did not find a difference in the risk of myocardial infarction: RR 0.89, 95% CI 0.22 to 3.65; I(2) = 0%. Based on six studies that included 729 participants, we did not find a difference in the risk of cerebrovascular accident: RR 1.48, 95% CI 0.46 to 4.83; I(2) = 0%. Based on six studies that included 624 participants, we did not find a difference in the risk of acute confusional state: RR 0.85, 95% CI 0.51 to 1.40; I(2) = 49%. Based on laboratory tests, the risk of deep vein thrombosis was decreased when no specific precautions or just early mobilization was used: RR 0.57, 95% CI 0.41 to 0.78; I(2) = 0%; (number needed to treat for an additional beneficial outcome (NNTB) = 3, 95% CI 2 to 7, based on a basal risk of 76%) but not when low molecular weight heparin was administered: RR 0.98, 95% CI 0.52 to 1.84; I(2) for heterogeneity between the two subgroups = 58%. For neuraxial blocks compared to general anaesthesia, we rated the quality of evidence as very low for mortality (at 0 to 30 days), pneumonia, myocardial infarction, cerebrovascular accident, acute confusional state, decreased rate of deep venous thrombosis in the absence of potent thromboprophylaxis, and return of patient to their own home. The number of studies comparing other anaesthetic techniques was limited. AUTHORS' CONCLUSIONS: We did not find a difference between the two techniques, except for deep venous thrombosis in the absence of potent thromboprophylaxis. The studies included a wide variety of clinical practices. The number of participants included in the review is insufficient to eliminate a difference between the two techniques in the majority of outcomes studied. Therefore, large randomized trials reflecting actual clinical practice are required before drawing final conclusions. PMID- 26899417 TI - Implementing cell contractility in filament-based cytoskeletal models. AB - Cells are known to respond over time to mechanical stimuli, even actively generating force at longer times. In this paper, a microstructural filament-based cytoskeletal network model is extended to incorporate this active response, and a computational study to assess the influence on relaxation behaviour was performed. The incorporation of an active response was achieved by including a strain energy function of contractile activity from the cross-linked actin filaments. A four-state chemical model and strain energy function was adopted, and generalisation to three dimensions and the macroscopic deformation field was performed by integration over the unit sphere. Computational results in MATLAB and ABAQUS/Explicit indicated an active cellular response over various time scales, dependent on contractile parameters. Important features such as force generation and increasing cell stiffness due to prestress are qualitatively predicted. The work in this paper can easily be extended to encompass other filament-based cytoskeletal models as well. PMID- 26899418 TI - In silico selection of an aptamer to estrogen receptor alpha using computational docking employing estrogen response elements as aptamer-alike molecules. AB - Aptamers, the chemical-antibody substitute to conventional antibodies, are primarily discovered through SELEX technology involving multi-round selections and enrichment. Circumventing conventional methodology, here we report an in silico selection of aptamers to estrogen receptor alpha (ERalpha) using RNA analogs of human estrogen response elements (EREs). The inverted repeat nature of ERE and the ability to form stable hairpins were used as criteria to obtain aptamer-alike sequences. Near-native RNA analogs of selected single stranded EREs were modelled and their likelihood to emerge as ERalpha aptamer was examined using AutoDock Vina, HADDOCK and PatchDock docking. These in silico predictions were validated by measuring the thermodynamic parameters of ERalpha -RNA interactions using isothermal titration calorimetry. Based on the in silico and in vitro results, we selected a candidate RNA (ERaptR4; 5'-GGGGUCAAGGUGACCCC-3') having a binding constant (Ka) of 1.02 +/- 0.1 * 10(8) M(-1) as an ERalpha aptamer. Target-specificity of the selected ERaptR4 aptamer was confirmed through cytochemistry and solid-phase immunoassays. Furthermore, stability analyses identified ERaptR4 resistant to serum and RNase A degradation in presence of ERalpha. Taken together, an efficient ERalpha-RNA aptamer is identified using a non-SELEX procedure of aptamer selection. The high-affinity and specificity can be utilized in detection of ERalpha in breast cancer and related diseases. PMID- 26899420 TI - Getting the smell of it--odour cues structure pollinator networks. AB - Floral visitors vary greatly among plant species and depend on the volatiles emitted by the flowers. Creeping thistle is normally visited by bees and bumblebees while common yarrow is rather visited by flies. Manipulating the flower volatiles caused pollinator communities to become more similar among the two plant species. Image credit: Robert Junker and Anna-Amelie Larue. In Focus: Larue, A.-A.C., Raguso, R.A. & Junker, R.R. (2015) Experimental manipulation of floral scent bouquets restructures flower-visitor interactions in the field. Journal of Animal Ecology, 85, 396-408. Pollinators use multiple cues to locate suitable flowers, and recent studies argue that flower volatiles are more important than previously believed. However, the role of volatiles is seldom separated from other cues. Larue, Raguso & Junker (2015) manipulated the volatile profile of two plants that are normally visited by different pollinators. Achillea millefolium is normally not visited by honeybees and bumblebees, but these pollinator groups did visit plants that were sprayed with volatiles from Cirsium arvense. Cirsium arvense, on the other hand, was less visited by honeybees and bumblebees when sprayed with volatiles from A. millefolium. These findings highlight the potential role of volatiles in structuring pollinator communities on plants. PMID- 26899419 TI - Social stress buffering by friends in childhood and adolescence: Effects on HPA and oxytocin activity. AB - Previous research has demonstrated that before puberty, parents are able to buffer, and often completely block, cortisol responses to social evaluative stressors (e.g., Trier Social Stress Test; TSST). However, after puberty, parents no longer provide a powerful buffer of the HPA axis from a social-evaluative stressor. The current study investigates whether friends can buffer the HPA axis in both children and adolescents compared to parents and whether similar stress ameliorating patterns can also be observed in oxytocin activity. A total of 109 participants (54 children aged 9-10 and 55 adolescents aged 15-16; half of each sex) completed the TSST and were randomly assigned to prepare for their speech with their parent or friend for 5 minutes beforehand. Salivary cortisol and urinary oxytocin were measured before and after the TSST. For children, cortisol responses were comparable regardless of who helped the child prepare the speech. For adolescents, however, friends actually amplified the cortisol response compared to parents. In addition, adolescents produced less oxytocin than children, as did males compared to females. Notably, for boys, oxytocin levels decreased across the session if participants prepared with a friend rather than their parent. The mean change was in the same direction but not significant for girls. These results indicate that friends do not take over the social buffering role by age 15-16, which may inform interventions in at-risk children and adolescents. PMID- 26899422 TI - Des differences, pourquoi? Transmission, maintenance and effects of phenotypic variance. AB - Despite the observed distribution of variable individual phenotypes, survival and reproductive performance in wild populations, models of population dynamics often focus on mean demographic rates. Populations are constituted by individuals with different phenotypes and thus different performances. However, many models of population dynamics provide no understanding of the influence of this phenotypic variation on population dynamics. In this paper, we investigate how the relationships between demographic rates and phenotype distribution influence the transmission and the upholding of phenotypic variation, and population dynamics. We used integral projection models to measure associations between differences of phenotypic trait (size or mass) among individuals and demographic rates, growth and inheritance, and then quantify the influence of phenotypic variation on population dynamics. We build an analytical and general model resulting from simplifications assuming small phenotypic variance. We illustrate our model with two case studies: a short- and a long-lived life history. Population growth rate r is determined by a Lotka style equation in which survival and fertility are averaged over a phenotypic distribution that changes with age. Here, we further decomposed r to show how much it is affected by shifts in phenotypic average as well as variance. We derived the elasticities of r to the first and second derivative of each demographic rate. In particular, we show that the nonlinearity of change in selective pressure with phenotype matters more to population dynamics than the strength of this selection. In other words, the variance of a given trait will be most important when the strength of selection increases (or decreases) nonlinearly with that trait. Inheritance shapes the distribution of newborn phenotypes. Even if newborns have a fixed average phenotype, the variance among newborns increases with phenotypic variance among mothers, strength of inheritance and developmental variation. We explain how the components of inheritance can influence phenotypic variance and thus the demographic rates and population dynamics. In particular, when mothers of different ages produce offspring of different mean phenotype, the inheritance function can have a large influence on both the mean and variance of the trait at different ages and thus on the population growth rate. We provide new tools to understand how phenotypic variation influences population dynamics and discuss in which life histories we expect this influence to be large. For instance, in our short-lived life history, individual variability has larger effect than in our long-lived life history. We conclude by indicating future directions of analysis. PMID- 26899423 TI - [Serious cutaneous reactions to galantamine hydrobromide (Reminyl(r) and generics)]. PMID- 26899421 TI - The evolution of labile traits in sex- and age-structured populations. AB - Many quantitative traits are labile (e.g. somatic growth rate, reproductive timing and investment), varying over the life cycle as a result of behavioural adaptation, developmental processes and plastic responses to the environment. At the population level, selection can alter the distribution of such traits across age classes and among generations. Despite a growing body of theoretical research exploring the evolutionary dynamics of labile traits, a data-driven framework for incorporating such traits into demographic models has not yet been developed. Integral projection models (IPMs) are increasingly being used to understand the interplay between changes in labile characters, life histories and population dynamics. One limitation of the IPM approach is that it relies on phenotypic associations between parents and offspring traits to capture inheritance. However, it is well-established that many different processes may drive these associations, and currently, no clear consensus has emerged on how to model micro evolutionary dynamics in an IPM framework. We show how to embed quantitative genetic models of inheritance of labile traits into age-structured, two-sex models that resemble standard IPMs. Commonly used statistical tools such as GLMs and their mixed model counterparts can then be used for model parameterization. We illustrate the methodology through development of a simple model of egg-laying date evolution, parameterized using data from a population of Great tits (Parus major). We demonstrate how our framework can be used to project the joint dynamics of species' traits and population density. We then develop a simple extension of the age-structured Price equation (ASPE) for two-sex populations, and apply this to examine the age-specific contributions of different processes to change in the mean phenotype and breeding value. The data-driven framework we outline here has the potential to facilitate greater insight into the nature of selection and its consequences in settings where focal traits vary over the lifetime through ontogeny, behavioural adaptation and phenotypic plasticity, as well as providing a potential bridge between theoretical and empirical studies of labile trait variation. PMID- 26899424 TI - Morphofunctional alterations in ventral tegmental area dopamine neurons in acute and prolonged opiates withdrawal. A computational perspective. AB - Dopamine (DA) neurons of the ventral tegmental area (VTA) play a key role in the neurobiological basis of goal-directed behaviors and addiction. Morphine (MOR) withdrawal induces acute and long-term changes in the morphology and physiology of VTA DA cells, but the mechanisms underlying these modifications are poorly understood. Because of their predictive value, computational models are a powerful tool in neurobiological research, and are often used to gain further insights and deeper understanding on the molecular and physiological mechanisms underlying the development of various psychiatric disorders. Here we present a biophysical model of a DA VTA neuron based on 3D morphological reconstruction and electrophysiological data, showing how opiates withdrawal-driven morphological and electrophysiological changes could affect the firing rate and discharge pattern. The model findings suggest how and to what extent a change in the balance of GABA/GLU inputs can take into account the experimentally observed hypofunction of VTA DA neurons during acute and prolonged withdrawal, whereas morphological changes may play a role in the increased excitability of VTA DA cell to opiate administration observed during opiate withdrawal. PMID- 26899425 TI - Amino-functionalized breath-figure cavities in polystyrene-alumina hybrid films: effect of particle concentration and dispersion. AB - We report the formation of breath-figure (BF) patterns with amino-functionalized cavities in a BF incompatible polystyrene (PS) by incorporating functionalized alumina nanoparticles. The particles were amphiphilic-modified and the modifier ratio was regulated to achieve a specific hydrophobic/hydrophilic balance of the particles. The influence of the physical and chemical properties of the particles like particle concentration, the hydrophobic/hydrophilic balance, etc., on particle dispersion in solvents having different polarity and the corresponding changes in the BF patterns have been studied. The amphiphilic-modified alumina particles could successfully assist the BF mechanism, generating uniform patterns in polystyrene films with the cavity walls decorated with the functionalized alumina particles, even from water-miscible solvents like THF. The possibility of fabricating free-standing micropatterned films by casting and drying the suspension under ambient conditions was also demonstrated. The present method opens up a simple route for producing functionalized BF cavities, which can be post-modified by a chemical route for various biological applications. PMID- 26899426 TI - Altitude-Induced Pulmonary Hypertension on One-Day Rapid Ascent of Mount Fuji: Incidence and Therapeutic Effects of Sildenafil. AB - AIMS: Exposure to high altitudes especially with rapid ascent may induce hypoxic pulmonary vasoconstriction (HPV) and pulmonary hypertension (PH) possibly leading to life-threatening high-altitude pulmonary edema (HAPE). The aim of the study was to evaluate the incidence of PH on a 1-day rapid ascent up Mount Fuji (3775 m) in recreational climbers and also to determine the effectiveness of sildenafil for this rapid ascent-induced PH as measured by echocardiography. METHODS AND RESULTS: Twenty-five subjects who climbed Mount Fuji showed significantly increased pulmonary artery systolic pressure (PASP) from 22.3 +/- 5.3 mmHg at sea level to 29.4 +/- 8.7 mmHg at 3775 m. Five subjects showed PASP >35 mmHg (35.6 46.2 mmHg, average 42.0 +/- 3.9 mmHg) and took oral sildenafil 50 mg after which PASP decreased significantly to 24.5 +/- 4.6 mmHg (18.7-31.0 mmHg) after 30 minutes. CONCLUSIONS: One-day rapid ascent of Mount Fuji may induce mild-to moderate PH and intervention with sildenafil can reduce this PH, suggesting that the therapeutic use of sildenafil would be more reasonable for the relatively infrequent occurrence of altitude-induced PH than its prophylactic use. PMID- 26899427 TI - Haemolymph from Mytilus galloprovincialis: Response to copper and temperature challenges studied by (1)H-NMR metabonomics. AB - Numerous studies on molluscs have been carried out to clarify the physiological roles of haemolymph serum proteins and haemocytes. However, little is known about the presence and functional role of the serum metabolites. In this study, Nuclear Magnetic Resonance (NMR) was used to assess whether changes of the metabolic profile of Mytilus galloprovincialis haemolymph may reflect alterations of the physiological status of the organisms due to environmental stressors, namely copper and temperature. Mussel haemolymph was taken from the posterior adductor muscle after a 4-day exposure to ambient (16 degrees C) or high temperature (24 degrees C) and in the absence or presence (5 MUg/L, 20 MUg/L, or 40 MUg/L) of sublethal copper (Cu(2+)). The total glutathione (GSH) concentration in the haemolymph of both control and treated mussels was minimal, indicating the absence of significant contaminations by muscle intracellular metabolites due to the sampling procedure. In the (1)H-NMR spectrum of haemolymph, 27 metabolites were identified unambiguously. The separate and combined effects of exposure to copper and temperature on the haemolymph metabolic profile were assessed by Principal Component Analysis (PCA) and Ranking-PCA multivariate analysis. Changes of the metabolomic profile due to copper exposure at 16 degrees C became detectable at a dose of 20 MUg/L copper. Alanine, lysine, serine, glutamine, glycogen, glucose and protein aliphatics played a major role in the classification of the metabolic changes according to the level of copper exposition. High temperature (24 degrees C) and high copper levels caused a coherent increase of a common set of metabolites (mostly glucose, serine, and lysine), indicating that the metabolic impairment due to high temperature is enforced by the presence of copper. Overall, the results demonstrate that, as for human blood plasma, the analysis of haemolymph metabolites represents a promising tool for the diagnosis of pollutant-induced stress syndrome in marine mussels. PMID- 26899428 TI - The Geography of Normative Climates: An Application to Adolescent Substance Use. AB - The existing research on risk factors for adolescent substance use highlights the importance of peers' direct influence on risky behaviors, yet two key limitations persist. First, there is considerably less attention to the ways in which peers shape overall (e.g., school-level) normative climates of attitudes and expectations about substance use, and, second, the role of the broader geographic contexts in which these climates are embedded is essentially neglected. In light of shifting trends in geographic differences in adolescent substance use, the current study uses data from the 2007 Nebraska Risk and Protective Factor Student Survey (n = 26,647; 80 % non-Hispanic White; 51 % female) to (a) explore whether geographic context shapes the character (permissiveness) and consistency (homogeneity) of normative climates and (b) examine the consequences (effects) of such climates on adolescent substance use risk across the rural-urban continuum. Normative climates are a consistent predictor of substance use, yet the geographic context in which schools are located matters for both the nature and influence of these climates, and the patterns differ between normative climates about alcohol and marijuana. These findings illustrate that school normative climates do indeed matter for substance use behavior, and the ways in which they do depend on their broader, geographic context. Thus, future research on youth's substance use should be attuned to these more nuanced distinctions. PMID- 26899429 TI - A comparative study on the analytical utility of atmospheric and low-pressure MALDI sources for the mass spectrometric characterization of peptides. AB - A comparative MS study was conducted on the analytical performance of two matrix assisted laser desorption/ionization (MALDI) sources that operated at either low pressure (~1Torr) or at atmospheric pressure. In both cases, the MALDI sources were attached to a linear ion trap mass spectrometer equipped with a two-stage ion funnel. The obtained results indicate that the limits of detection, in the analysis of identical peptide samples, were much lower with the source that was operated slightly below the 1-Torr pressure. In the low-pressure (LP) MALDI source, ion signals were observed at a laser fluence that was considerably lower than the one determining the appearance of ion signals in the atmospheric pressure (AP) MALDI source. When the near-threshold laser fluences were used to record MALDI MS spectra at 1-Torr and 750-Torr pressures, the level of chemical noise at the 1-Torr pressure was much lower compared to that at AP. The dependency of the analyte ion signals on the accelerating field which dragged the ions from the MALDI plate to the MS analyzer are presented for the LP and AP MALDI sources. The study indicates that the laser fluence, background gas pressure, and field accelerating the ions away from a MALDI plate were the main parameters which determined the ion yield, signal-to-noise (S/N) ratios, the fragmentation of the analyte ions, and adduct formation in the LP and AP MALDI MS methods. The presented results can be helpful for a deeper insight into the mechanisms responsible for the ion formation in MALDI. PMID- 26899430 TI - An in vitro selection for small molecule induced switching RNA molecules. AB - The selection of RNA and DNA aptamers now has a long history. However, the ability to directly select for conformational changes upon ligand binding has remained elusive. These difficulties have stymied attempts at making small molecule responsive strand displacement circuitry as well as synthetic riboswitches. Herein we present a detailed strand displacement based selection protocol to directly select for RNA molecules with switching activity. The library was based on a previously selected thiamine pyrophosphate riboswitch. The fully in vitro methodology gave sequences that showed strong strand displacement activity in the presence of thiamine pyrophosphate. Further, the selected sequences possessed riboswitch activity similar to that of natural riboswitches. The presented methodology should aid in the design of more complex, environmentally responsive strand displacement circuitry and in the selection of riboswitches responsive to toxic ligands. PMID- 26899431 TI - The Economic Burden of Post-prandial Hyperglycemia (PPH) Among People with Type 1 and Type 2 Diabetes in Three Countries. AB - INTRODUCTION: Post-prandial hyperglycemia (PPH) among people with diabetes is a well-known clinical challenge to diabetes management. While the economic burden of diabetes is well studied, little is known about economic costs specific to PPH. The purpose of this study was to investigate costs of PPH related to work, diabetes management, and use of healthcare resources among people with diabetes taking bolus insulin. METHODS: Data were collected in a web survey of 906 adults with type 1 (39%) and type 2 (61%) diabetes taking bolus insulin in Germany (34%), the UK (26%), and the USA (40%). RESULTS: Sixty-two percent of respondents experienced PPH in the past week, and respondents averaged 1.7 episodes per week. Working respondents indicated that PPH affected their work productivity: 27% missed work time and 71% experienced work productivity issues while at work due to a recent episode of PPH. In terms of diabetes management, respondents with PPH in the past week measured their blood glucose (BG) more frequently than those without PPH (3.7 vs. 2.5 times/day, P < 0.001). PPH was also significantly associated with greater use of healthcare resources. Compared to those without PPH, respondents with PPH reported greater contact with healthcare professionals related to diabetes in the past year (5.5 vs. 4.4 visits, P < 0.001; 2.7 vs. 1.4 calls/emails, P < 0.001) and were more likely to report medical complications related to diabetes (72% vs. 55%, P < 0.001). Average annual costs associated with PPH due to missed work time, additional BG test strips, and physician visits were estimated to be $1239 USD per employed person in the USA. CONCLUSION: Results indicate that PPH is associated with greater economic costs and that reducing the incidence of PPH would help mitigate such costs. Additional research is needed to better understand costs associated with PPH that may be more difficult to measure, as well as more long-term impacts and costs. FUNDING: Novo Nordisk. PMID- 26899432 TI - Cystatin C- and Creatinine-Based Estimates of Glomerular Filtration Rate in Dapagliflozin Phase 3 Clinical Trials. AB - INTRODUCTION: To compare estimated glomerular filtration rate measured by serum creatinine (eGFRcr) and serum cystatin C (eGFRcys) in patients with type 2 diabetes mellitus from dapagliflozin clinical trials. METHODS: Post hoc analysis of data pooled from 9 phase 3, randomized, placebo-controlled, 24-week trials of dapagliflozin. The correlation between eGFRcr and eGFRcys was modeled by a simple linear regression. The proportions of patients with eGFR 30 to <60 and >=60 mL/min/1.73 m(2) based on creatinine versus cystatin C were compared. RESULTS: Of 4745 total patients, 4294 (90.5%) had serum cystatin C data available for calculation of eGFRcys. The correlation between eGFRcr and eGFRcys was poor (R (2) = 30%). Of patients with eGFRcr 30 to <60 mL/min/1.73 m(2), 66% had eGFR >=60 when recalculated based on cystatin C. Among patients with eGFRcr >=60 mL/min/1.73 m(2), 95.8% had eGFR >=60 when estimated using cystatin C. Decreases in HbA1c, body weight, and systolic blood pressure with dapagliflozin were similar among patient subgroups defined by either eGFR estimate and were statistically significant and clinically meaningful with dapagliflozin 10 mg/day in most subgroups. CONCLUSION: The correlation between eGFRcr and eGFRcys was poor. Renal function assessed by eGFRcr may be underestimated, and some patients may be misdiagnosed with chronic kidney disease and/or unjustifiably deemed ineligible for certain antidiabetes medications. This is in consonance with guidelines suggesting using eGFRcys as a confirmatory measure when eGFRcr is between 45 and <60 mL/min/1.73 m(2) with no evidence of kidney damage and/or in other situations where eGFRcr may be unreliable. FUNDING: AstraZeneca. PMID- 26899433 TI - Reduced volume of gray matter in patients with trigeminal neuralgia. AB - Accumulating evidence from brain structural imaging studies has supported that chronic pain could induce changes in brain gray matter volume. However, few studies have focused on the gray matter alterations of Trigeminal neuralgia (TN). In this study, twenty-eight TN patients (thirteen females; mean age, 45.86 years +/-11.17) and 28 healthy controls (HC; thirteen females; mean age, 44.89 years +/ 7.67) were included. Using voxel-based morphometry (VBM), we detected abnormalities in gray matter volume in the TN patients. Based on a voxel-wise analysis, the TN group showed significantly decreased gray matter volume in the bilateral superior/middle temporal gyrus (STG/MTG), bilateral parahippocampus, left anterior cingulate cortex (ACC), caudate nucleus, right fusiform gyrus, and right cerebellum compared with the HC. In addition, we found that the gray matter volume in the bilateral STG/MTG was negatively correlated with the duration of TN. These results provide compelling evidence for gray matter abnormalities in TN and suggest that the duration of TN may be a critical factor associated with brain alterations. PMID- 26899434 TI - Systematic Surface Phase Transition of Ag Thin Films by Iodine Functionalization at Room Temperature: Evolution of Optoelectronic and Texture Properties. AB - We show a simple room temperature surface functionalization approach using iodine vapour to control a surface phase transition from cubic silver (Ag) of thin films into wurtzite silver-iodid (beta-AgI) films. A combination of surface characterization techniques (optical, electronical and structural characterization) reveal distinct physical properties of the new surface phase. We discuss the AgI thin film formation dynamics and related transformation of physical properties by determining the work-function, dielectric constant and pyroelectric behavior together with morphological and structural thin film properties such as layer thickness, grain structure and texture formation. Notable results are: (i) a remarkable increase of the work-function (by 0.9 eV) of the Ag thin layer after short a iodine exposure time (<=60 s), with simultaneous increase of the thin film transparency (by two orders of magnitude), (ii) pinning of the Fermi level at the valance band maximum upon iodine functionalization, (iii) 84% of all crystallites grain were aligned as a result of the evolution of an internal electric field. Realizing a nano-scale layer stack composed of a dielectric AgI layer on top of a metallic thin Ag layer with such a simple method has some technological implications e.g. to realize optical elements such as planar optical waveguides. PMID- 26899435 TI - Borylation of Olefin C-H Bond via Aryl to Vinyl Palladium 1,4-Migration. AB - The aryl to vinyl palladium 1,4-migration was realized for the first time. The generated alkenyl palladium species was trapped by diboron reagents under Miyaura borylation conditions, providing a new method to synthesize beta,beta disubstituted vinylboronates. The excellent regioselectivity and broad substrate scope were observed for this novel transformation. PMID- 26899436 TI - Preferred supplier contracts in post-patent prescription drug markets. AB - In recent years, the expiration of patents for large drug classes has increased the importance of post-patent drug markets. However, previous research has focused solely on patent drug markets. In this study, the authors evaluate the influence of preferred supplier contracts, the German approach to tendering, in post-patent drug markets using a hierarchical market share attraction model. The authors find that preferred supplier contracts are a powerful strategic instrument for generic manufacturers in a highly competitive environment. They quantify the effects of signing a preferred supplier contract and show that brand name manufacturers are vulnerable to tendering. Therefore, brand-name manufacturers should readjust their strategies and consider including preferred supplier contracts in their marketing mix. In addition, the authors employ a simulation to demonstrate that a first-mover advantage might be gained from signing a preferred supplier contract. Furthermore, their results can be used as a blueprint for decision makers in the pharmaceutical industry to assess the market share effects of different contracting strategies regarding preferred supplier contracts. PMID- 26899437 TI - Concentration of glycosaminoglycan in ovariectomized mice uterus after treatment with ovarian steroids. AB - The aim of this study was to evaluate the amount of non- and sulfated glycosaminoglycans in the ovariectomized mice uterus, after treatment with ovarian steroids. For this purpose, 50 adult female mice were divided into five groups with 10 animals/each: control group: CG (ovary intact), and ovariectomized groups: OG (vehicle), EG (estradiol), PG (progesterone) and EPG (estradiol combined to progesterone). The treatments started 30 days after ovariectomy. All the animals were treated for 50 consecutive days. These hormones were administered in a sterile oily solution via gavage. Twenty-four hours after the last treatment, all animals were euthanized, removing the uterine horn for biochemical analyses. To quantify, the hyaluronic acid (HA) used ELISA-like fluorometric assay, and the sulfated glycosaminoglycans (GAGs) used agarose gel electrophoresis. The amount of HA was significantly higher in the group treated with progesterone (PG) compared to the others groups (p < 0.05), and in the group treated with estradiol (EG), the amount of chondroitin/dermatan sulfate was significantly higher compared to the others groups (p < 0.05), and in the group treated with progesterone (PG), the amount of heparan sulfate was significantly lower compared to the others groups, except to control group (p < 0.05). Our results showed that the estroprogestative therapy after long time (50 days) profoundly affected the amount of glycosaminoglycans in uterine. These changes may be indicative of uterine pathology such as the development of tumor. PMID- 26899438 TI - Vitamin D-binding protein: one more piece in the puzzle of acromegalic osteopathy? PMID- 26899439 TI - Type 2 diabetes-related foot care knowledge and foot self-care practice interventions in the United States: a systematic review of the literature. AB - INTRODUCTION: The purpose of this systematic literature review is to review published studies on foot care knowledge and foot care practice interventions as part of diabetic foot care self-management interventions. METHODS: Medline, CINAHL, CENTRAL, and Cochrane Central Register of Controlled Trials databases were searched. References from the included studies were reviewed to identify any missing studies that could be included. Only foot care knowledge and foot care practice intervention studies that focused on the person living with type 2 diabetes were included in this review. Author, study design, sample, intervention, and results were extracted. RESULTS: Thirty studies met the inclusion criteria and were classified according to randomized controlled trial (n=9), survey design (n=13), cohort studies (n=4), cross-sectional studies (n=2), qualitative studies (n=2), and case series (n=1). Improving lower extremity complications associated with type 2 diabetes can be done through effective foot care interventions that include foot care knowledge and foot care practices. CONCLUSION: Preventing these complications, understanding the risk factors, and having the ability to manage complications outside of the clinical encounter is an important part of a diabetes foot self-care management program. Interventions and research studies that aim to reduce lower extremity complications are still lacking. Further research is needed to test foot care interventions across multiple populations and geographic locations. PMID- 26899440 TI - Antidiabetic potentials of ethanolic extract of Aristolochia ringens (Vahl.) roots. AB - ETHNOPHARMACOLOGICAL IMPORTANCE: Oral administration of alcoholic decoctions of Aristolochia ringens is used extensively by Traditional Medicine Practitioners (TMP) of Yoruba heritage in South west, Nigeria for the management of diabetes and its associated complications. AIM OF THE STUDY: To assess the potentials of root ethanolic extract of Aristolochia ringens V. (REAR) in the management of diabetes using chemical induced experimental animal model. MATERIALS AND METHODS: Qualitative and quantitative analyses were carried out to elucidate chemical constituents of the REAR extract using phytochemical analyses and gas chromatography-mass spectrometry (GC-MS) technique. Streptozotocin (STZ)-induced diabetic rats were orally administered with 75, 150 and 300mg/kg body weight of the REAR, once a day and the blood glucose (GLU) levels were monitored for 14 days. Mechanisms of GLU lowering effect were investigated by performing oral glucose tolerance test (OGTT) and modulation of diabetes associated biomarkers including hepatic glycogen (GLY), GLU, alpha amylase (alphaAMY) and glucose-6 phosphate dehydrogenase (GPDH) by the extract. RESULTS: Extraction from A. ringens roots using ethanol/water (70/30) yielded 10.25% w/w REAR extract. Preliminary phytochemical profiling of REAR extract revealed the presence of flavonoids (23.03%), phenols (19.15%), alkaloids (16.13%), tannins (4.21%), saponins (1.44%) and GC-MS analyses showed that bulk of the extract was constituted by aristolone (92.3%). Oral administration of 300mg/kg b. wt. REAR extract caused significant reduction (>90%) in hyperglycemia to normal GLU level (<= 120mg/dl) after 11 days of treatment. Lower doses of 75 and 150mg/kg b. wt. caused similar effect after 13 days. The extract also normalized postprandial GLU to baseline level within 90-120min. Also, GLY concentrations and GPDH activity were significantly increased, whereas GLU levels and alphaAMY activity were reduced in the liver of diabetic rats treated with REAR extract compared to values in non-treated diabetic group. CONCLUSION: These findings revealed that ethanolic extract from A. ringens root possess antihyperglycemic activity and the data established its usage in folkloric decoctions for management of diabetes. PMID- 26899441 TI - Anti-depressant effects of Gastrodia elata Blume and its compounds gastrodin and 4-hydroxybenzyl alcohol, via the monoaminergic system and neuronal cytoskeletal remodeling. AB - ETHNOPHARMACOLOGY RELEVANCE: Gastrodia elata Blume is a highly valuable traditional Chinese medicine used in the treatment of depression. However, compounds with antidepressant effects in water extracts of G. elata Bl. (WGE) have not been identified. The aims of this study were to determine the major antidepressant compound in WGE and to evaluate the antidepressant effects of WGE and its active compounds which involved the monoaminergic system and neuronal cytoskeletal remodeling. MATERIALS AND METHODS: Gastrodin (GAS) and 4 hydroxybenzyl alcohol (HBA) in WGE, were analyzed with high-performance liquid chromatography (HPLC)-ultraviolet detection. The forced swimming test (FST) was used to induce depression-like symptoms in 9 weeks old male Sprague-Dawley rats. The open field test (OFT) was used to measure anxiety after WGE, GAS, and HBA treatments. The levels of monoamine such as serotonin (5-HT), dopamine (DA), and their metabolites 5-hydroxyindoleacetic acid (5-HIAA), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) were measured using HPLC electrochemical detection. Western blotting was used to examine the 5-HT1A receptor and the neuronal cytoskeleton remodeling-related proteins, Slit, dihydropyrimidinase-related protein 2 (DPYSL2, also called CRMP2), Ras homologous member A (RhoA), and profilin 1 (PFN1) in vivo. Slit1 expression was evaluated in Hs683 cell line after treated with WGE (0.5mg/mL), GAS (50, 100 and 100MUM), and HBA (50, 100 and 100MUM). RESULTS: Oral administration of WGE (500mg/kg bw), GAS (100mg/kg bw), and HBA (100mg/kg bw) exhibited the anti-depressant effect by significantly reducing the immobility time in FST, monoamine metabolism including the 5-HT to 5-HIAA in the hippocampus and DA to DOPAC and HVA ratios in the frontal cortex, amygdala, and hippocampus. In the hippocampus, the expression of the neuronal cytoskeleton remodeling-related negative regulators Slit1 and RhoA were significantly down-regulated. In addition, the positive regulators CRMP2 and PFN1 were significantly up-regulated following GAS, HBA, and WGE treatments. Moreover, WGE, GAS, and HBA were directly down-regulated Slit1 expression in Hs683 cells. CONCLUSION: WGE, GAS, and HBA exhibited potential anti-depressant effects in rats by decreasing monoamine metabolism and modulated cytoskeleton remodeling-related protein expression in the Slit-Robo pathway. These results suggest that WGE can be used as agent for depressive prevention. PMID- 26899442 TI - Urinary NMR-based metabolomic analysis of rats possessing variable sperm count following orally administered Eurycoma longifolia extracts of different quassinoid levels. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Eurycoma longifolia (Tongkat Ali, TA) roots have been ethnically used as a remedy to boost male sexual desire, libido, energy and fertility. AIM OF THE STUDY: The study evaluated the effect of TA extracts with different quassinoid levels on rats sperm count and examined corresponding post treatment urinary metabolic changes. MATERIALS AND METHODS: Twenty-four male Sprague-Dawley rats, categorized into 4 groups of 6 rats each, were orally administered for 48 days with water for the control (group 1), 125mg/kg of TA water extract (TAW, group 2), 125mg/kg of TA quassinoid-poor extract (TAQP, group 3) and 21mg/kg of TA quassinoid-rich extract (TAQR, group 4). Upon completion of the 48-day treatment, the urine samples were analyzed by NMR and the animals were subsequently sacrificed for sperm count analysis. The urine profiles were categorized according to sperm count level. RESULTS: The results showed that the sperm count in TAW- and TAQR-treated groups was significantly higher compared to the TAQP-administered and control groups. The orthogonal partial least squares discriminant analysis (OPLS-DA) model indicated a clear separation among the urine profiles with respect to sperm count level. Urine (1)H-NMR profiles of the high-sperm count group contained higher concentrations of trigonelline, alanine, benzoic acid and higher intensity of a signal at 3.42ppm, while ethanol was at higher concentration in the normal-sperm count group. CONCLUSIONS: The results proved the efficacy of quassinoids on sperm count increase in rats and provided quantitative markers in urine suitable for analysis of sperm profile and male fertility status. PMID- 26899445 TI - Underlying mechanisms and chemical/biochemical therapeutic approaches to ameliorate protein misfolding neurodegenerative diseases. AB - Protein misfolding and inclusion body formations are common events in neurodegenerative diseases characterized by deposition of misfolded proteins inside or outside of neurons, and are commonly referred to as "protein misfolding neurodegenerative diseases" (PMNDs). These phenotypically diverse but biochemically similar aggregates suggest a highly conserved molecular mechanism of pathogenesis. These challenges are magnified by presence of mutations that render individual proteins subject to misfolding and/or aggregation. Cell proteostasis network and molecular chaperoning are maintaining cell proteome to preserve the protein folding, refolding, oligomerization, or disaggregation, and play formidable tasks to maintain the health of organism in the face of developmental changes, environmental insults, and rigors of aging. Maintenance of cell proteome requires the orchestration of major pathways of the cellular proteostasis network (heat shock response (HSR) in the cytosol and the unfolded protein response (UPR) in the endoplasmic reticulum). Proteostasis responses culminate in transcriptional and post-transcriptional programs that up-regulate the homeostatic mechanisms. Proteostasis is strongly influenced by the general properties of individual proteins for folding, misfolding, and aggregation. We examine a growing body of evidence establishing that when cellular proteostasis goes awry, it can be reestablished by deliberate chemical and biological interventions. We first try to introduce some new chemical approaches to prevent the misfolding or aggregation of specific proteins via direct binding interactions. We then start with approaches that employ chemicals or biological agents to enhance the general capacity of the proteostasis network. We finish with evidence that synergy is achieved with the combination of mechanistically distinct approaches to reestablish organ proteostasis. (c) 2016 BioFactors, 43(6):737-759, 2017. PMID- 26899446 TI - The comparison of microRNA profile of the dermis between the young and elderly. AB - BACKGROUND: Skin aging is a process of structural and compositional remodeling that can be manifested as wrinkling and sagging. Remarkably, the dermis plays a dominant role in the process of skin aging. Recent studies suggest that microRNAs (miRNAs) may play a role in the regulation of gene expression in organism aging. However, studies about age-related miRNAs in human skin remain limited. OBJECTIVE: To obtain an overall view of miRNAs expression in human aged dermis by comparison of dermis samples between young and elderly, construct the miRNA-gene network and reveal the pivotal miRNAs in the regulatory network. METHODS: Human dermis tissue was obtained from 12 donors, including 6 of young group and 6 of elderly one. The miRNA microarray and data analysis were performed. Target genes of differentially expressed miRNAs were predicted, followed by a gene ontology and pathway enrichment analysis. A miRNA-gene-network was then constructed, and the pivotal miRNAs in the network was revealed. Primary human dermal fibroblasts (HDFs) were isolated, and the cellular senescence was induced by serial passaging. Alteration in the expression of miRNAs between young and senescent fibroblasts was evaluated by real-time quantitative RT-PCR. MiR-34b-5p mimics were transfected into primary HDFs. Subsequent cell cycle analysis was performed and expression level of COL1A1, elastin and MMP-1 were evaluated. RESULTS: The expression of a total of 40 miRNAs (25 upregulated and 15 downregulated) was found to be significantly altered in aged dermis compared with young dermis. Real time quantitative PCR results confirmed the differential expression of miR-34 family and miR-29 family between young and aged dermis. A computational approach demonstrated that predicted target genes of the miRNA profile were found to be mainly involved in processes including cell adhesion, collagen synthesis, positive or negative regulation of transcription, as well as pathways such as insulin signaling pathway, ErbB (Erythroblastic Leukemia Viral Oncogene Homolog) signaling pathway and Focal adhesion pathway. The miRNA-Gene-Network revealed that miR-34 family, miR-29 family and miR-424 may play a dominant role in the regulatory network. A similar miRNA alteration was observed in senescent fibroblasts in vitro, and the age-related miRNA profile may interact with p16 pathway to regulate the fibroblasts' senescence. Additionally, transfection of miR-34b-5p mimics induced cell cycle arrest in HDFs, decreased the expression of both COL1A1 and elastin and increased MMP-1 expression. CONCLUSION: The miR-34 family and miR-29 family expressed differentially in young and aged dermis. MiR 34 in HDFs modulated the cell function and expression of MMP-1, COL1A1 and elastin. The miRNAs may play critical roles in affecting dermis aging. PMID- 26899447 TI - Place of diagnostic tools in the identification of Anaerobiospirillum succiniciproducens bacteraemia. AB - Anaerobiospirillum succiniciproducens is a rare but potentially lethal pathogen. We report a case of A. succiniciproducens bloodstream infection in a 55-year-old man hospitalized for pelvic trauma. The strain was identified by 16sRNA sequencing after several failures of identification by MALDI-TOF MS. The strain was susceptible to beta-lactam antibiotics and ciprofloxacin, but resistant to macrolides and clindamycin. Identification tools must be improved to enhance our knowledge on this rare pathogen and to define optimal therapy. PMID- 26899449 TI - Role of dimethyl fumarate in oxidative stress of multiple sclerosis: A review. AB - Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS affecting both white and grey matter. Inflammation and oxidative stress are also thought to promote tissue damage in multiple sclerosis. Recent data point at an important role of anti-oxidative pathways for tissue protection in chronic MS, particularly involving the transcription factor nuclear factor (erythroid-derived 2)-related factor 2 (Nrf2). Thus, novel therapeutics enhancing cellular resistance to free radicals could prove useful for MS treatment. Oxidative stress and anti-oxidative pathways are important players in MS pathophysiology and constitute a promising target for future MS therapy with dimethyl fumarate. The clinical utility of DMF in multiple sclerosis is being explored through phase III trials with BG-12, which is an oral therapeutic agent. Currently a wide research is going on to find out the exact mechanism of DMF, till date it is not clear. Based on strong signals of nephrotoxicity in non-humans and the theoretical risk of renal cell cancer from intracellular accumulation of fumarate, post-marketing study of a large population of patients will be necessary to fully assess the long-term safety of dimethyl fumarate. The current treatment goals are to shorten the duration and severity of relapses, prolong the time between relapses, and delay progression of disability. In this regard, dimethyl fumarate offers a promising alternative to orally administered fingolimod (GILENYA) or teriflunomide (AUBAGIO), which are currently marketed in the United States under FDA-mandated Risk Evaluation and Mitigation Strategy (REMS) programs because of serious safety concerns. More clinical experience with all three agents will be necessary to differentiate the tolerability of long-term therapy for patients diagnosed with multiple sclerosis. This write-up provides the detailed information of dimethyl fumarate in treating the neuro disease, multiple sclerosis and its mechanism involved via oxidative stress pathway. The rapid screening methods are also need to be developed to estimate DMF in biological samples to perform and proceed for further investigations. PMID- 26899448 TI - Clostridium kogasensis sp. nov., a novel member of the genus Clostridium, isolated from soil under a corroded gas pipeline. AB - Two bacterial strains, YHK0403(T) and YHK0508, isolated from soil under a corroded gas pipe line, were revealed as Gram-negative, obligately anaerobic, spore-forming and mesophilic bacteria. The cells were rod-shaped and motile by means of peritrichous flagella. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the isolates were members of the genus Clostridium and were the most closely related to Clostridium scatologenes KCTC 5588(T) (95.8% sequence similarity), followed by Clostridium magnum KCTC 15177(T) (95.8%), Clostridium drakei KCTC 5440(T) (95.7%) and Clostridium tyrobutyricum KCTC 5387(T) (94.9%). The G + C contents of the isolates were 29.6 mol%. Peptidoglycan in the cell wall was of the A1gamma type with meso-diaminopimelic acid. The major polar lipid was diphosphatidylglycerol (DPG), and other minor lipids were revealed as phosphatidylglycerol (PG), phosphatidylethanolamine (PE), two unknown glycolipids (GL1 and GL2), an unknown aminoglycolipid (NGL), two unknown aminophospholipids (PN1 and PN2) and four unknown phospholipids (PL1 to PL4). Predominant fatty acids were C16:0 and C16:1cis9 DMA. The major end products from glucose fermentation were identified as butyrate (12.2 mmol) and acetate (9.8 mmol). Collectively, the results from a wide range of phenotypic tests, chemotaxonomic tests, and phylogenetic analysis indicated that the two isolates represent novel species of the genus Clostridium, for which the name Clostridium kogasensis sp. nov. (type strain, YHK0403(T) = KCTC 15258(T) = JCM 18719(T)) is proposed. PMID- 26899450 TI - Rapid N-glycan release from glycoproteins using immobilized PNGase F microcolumns. AB - N-glycosylation profiling of glycoprotein biotherapeutics is an essential step in each phase of product development in the biopharmaceutical industry. For example, during clone selection, hundreds of clones should be analyzed quickly from limited amounts of samples. On the other hand, identification of disease related glycosylation alterations can serve as early indicators (glycobiomarkers) for various pathological conditions in the biomedical field. Therefore, there is a growing demand for rapid and easy to automate sample preparation methods for N glycosylation analysis. In this paper, we report on the design and implementation of immobilized recombinant glutathione-S-transferase (GST) tagged PNGase F enzyme microcolumns for rapid and efficient removal of N-linked carbohydrates from glycoproteins. Digestion speed and efficiency were compared to conventional in solution based protocols. The use of PNGase F functionalized microcolumns resulted in efficient N-glycan removal in 10min from all major N-linked glycoprotein types of: (i) neutral (IgG), (ii) highly sialylated (fetuin), and (iii) high mannose (ribonuclease B) carbohydrate containing glycoprotein standards. The approach can be readily applied to automated sample preparation systems, such as liquid handling robots. PMID- 26899451 TI - Mechanism of action of brexpiprazole: comparison with aripiprazole. AB - Brexpiprazole is a new therapeutic agent that was recently approved for the treatment of schizophrenia and for the adjunctive treatment of major depressive disorder. Brexpiprazole has features that both overlap and contrast with a related molecule, aripiprazole, and these features are discussed here. PMID- 26899455 TI - The Ball and Chain of Polyubiquitin Structures. AB - Ubiquitylation is a post-translational modification implicated in several different cellular pathways. The possibility of forming chains through covalent crosslinking between any of the seven lysines, or the initial methionine, and the C terminus of another moiety provides ubiquitin (Ub) with special flexibility in its function in signalling. Here, we review the knowledge accumulated over the past several years about the functions and structural features of polyUb chains. This analysis reveals the need to understand further the functional role of some of the linkages and the structural code that determines recognition of polyUbs by protein partners. PMID- 26899454 TI - Recommendations for utilization of the paracorporeal lung assist device in neonates and young children with pulmonary hypertension. AB - The management of decompensating critically ill children with severe PH is extremely challenging and requires a multidisciplinary approach. Unfortunately, even with optimal care, these children might continue to deteriorate and develop inadequate systemic perfusion and at times cardiac arrest secondary to a pulmonary hypertensive crisis. Tools to support these children are limited, and at times, the team should proceed with offering extracorporeal support, especially in newly diagnosed patients who have not benefitted from medical therapy prior to their acute deterioration, in patients with severe pulmonary venous disease and in patients with alveolar capillary dysplasia. Currently, the only approved mode for extracorporeal support in pediatric patients with PH eligible for lung transplantation is ECMO. To decrease the risks associated with ECMO, and offer potential for increased duration of support, extubation, and rehabilitation, we transitioned four small children with refractory PH from ECMO to a device comprising an oxygenator interposed between the PA and LA. This work describes in great detail our experience with this mode of support with emphasis on exclusion criteria, the implantation procedure, and the post-implantation management. PMID- 26899456 TI - Sparse cliques trump scale-free networks in coordination and competition. AB - Cooperative behavior, a natural, pervasive and yet puzzling phenomenon, can be significantly enhanced by networks. Many studies have shown how global network characteristics affect cooperation; however, it is difficult to understand how this occurs based on global factors alone, low-level network building blocks, or motifs are necessary. In this work, we systematically alter the structure of scale-free and clique networks and show, through a stochastic evolutionary game theory model, that cooperation on cliques increases linearly with community motif count. We further show that, for reactive stochastic strategies, network modularity improves cooperation in the anti-coordination Snowdrift game and the Prisoner's Dilemma game but not in the Stag Hunt coordination game. We also confirm the negative effect of the scale-free graph on cooperation when effective payoffs are used. On the flip side, clique graphs are highly cooperative across social environments. Adding cycles to the acyclic scale-free graph increases cooperation when multiple games are considered; however, cycles have the opposite effect on how forgiving agents are when playing the Prisoner's Dilemma game. PMID- 26899458 TI - Neural networks applied to determine the thermophysical properties of amino acid based ionic liquids. AB - A series of models based on artificial neural networks (ANNs) have been designed to estimate the thermophysical properties of different amino acid-based ionic liquids (AAILs). Three different databases of AAILs were modeled using these algorithms with the goal set to estimate the density, viscosity, refractive index, ionic conductivity, and thermal expansion coefficient, and requiring only data regarding temperature and electronic polarizability of the chemicals. Additionally, a global model was designed combining all of the databases to determine the robustness of the method. In general, the results were successful, reaching mean prediction errors below 1% in many cases, as well as a statistically reliable and accurate global model. Attaining these successful models is a relevant fact as AAILs are novel biodegradable and biocompatible compounds which may soon make their way into the health sector forming a part of useful biomedical applications. Therefore, understanding the behavior and being able to estimate their thermophysical properties becomes crucial. PMID- 26899457 TI - Microfluidic devices with templated regular macroporous structures for HIV viral capture. AB - There is a need to develop inexpensive, portable and easy-to-use devices for viral sample processing for resource-limited settings. Here we offer a solution to efficient virus capture by incorporating macroporous materials with regular structures into microfluidic devices for affinity chromatography. Two-dimensional simulations were first conducted to investigate the effects of two structures, a nanopost array and a spherical pore network, on nanoparticle capture. Then, the two structures were created in polymers by templating anodic aluminum oxide films and 3D close-packed silica particles, respectively. When the microdevices containing functionalized porous materials were tested for human immunodeficiency virus (HIV) isolation, capture efficiencies of 80-99% were achieved under a continuous flow. Comparatively, functionalized flatbed microchannels captured around 10% of HIV particles. As the characteristic dimensions of the nanostructures are tunable, such devices can be adapted for the capture of different submicron bioparticles. The high capture efficiency and easy-to-operate nature suit the needs of resource-limited settings and may find applications in point-of-care diagnostics. PMID- 26899459 TI - Ketamine as Rescue Treatment for Difficult-to-Sedate Severe Acute Behavioral Disturbance in the Emergency Department. AB - STUDY OBJECTIVE: We investigate the effectiveness and safety of ketamine to sedate patients with severe acute behavioral disturbance who have failed previous attempts at sedation. METHODS: This was a prospective study of patients given ketamine for sedation who had failed previous sedation attempts. Patients with severe acute behavioral disturbance requiring parenteral sedation were treated with a standardized sedation protocol including droperidol. Demographics, drug dose, observations, and adverse effects were recorded. The primary outcome was the number of patients who failed to sedate within 120 minutes of ketamine administration or requiring further sedation within 1 hour. RESULTS: Forty-nine patients from 2 hospitals were administered rescue ketamine during 27 months; median age was 37 years (range 20-82 years); 28 were men. Police were involved with 20 patients. Previous sedation included droperidol (10 mg; 1), droperidol (10+10 mg; 33), droperidol (10+10+5 mg; 1), droperidol (10+10+10 mg; 11), and combinations of droperidol and benzodiazepines (2) and midazolam alone (1). The median dose of ketamine was 300 mg (range 50 to 500 mg). Five patients (10%; 95% confidence interval 4% to 23%) were not sedated within 120 minutes or required additional sedation within 1 hour. Four of 5 patients received 200 mg or less. Median time to sedation postketamine was 20 minutes (interquartile range 10 to 30 minutes; 2 to 500 minutes). Three patients (6%) had adverse effects, 2 had vomiting, and a third had a transient oxygen desaturation to 90% after ketamine that responded to oxygen. CONCLUSION: Ketamine appeared effective and did not cause obvious harm in this small sample and is a potential option for patients who have failed previous attempts at sedation. A dose of 4 to 5 mg/kg is suggested, and doses less than 200 mg are associated with treatment failure. PMID- 26899460 TI - Let's "Take 'Em Down" With a Ketamine Blow Dart. PMID- 26899461 TI - Differences in prescribing psychotropic drugs for elderly with depression. AB - OBJECTIVE: The escalating tendency of elderly population aged 65 and over, which grown up to 9% since 2001 in Taiwan, remarks the important issue of mental health among ageing population. Depression in the elderly is frequently undetected or inadequately treated. This study aimed to investigate the pharmacotherapy of elderly patients with depression by comparing the patterns of prescribing psychotropic drugs (psychotropics) of psychiatrists and non-psychiatrists. METHODS: A random sampling of 5% of inpatients from the National Health Insurance (NHI) database in Taiwan from 2001 to 2003 was selected. In all, 1058 (0.9%) inpatients aged 65 and older with a diagnosis of any depressive disorder were included. The psychotropic prescribing pattern and the dosages used were analysed and compared. Physician specialties were based on the record of NHI database. Non psychiatrists were defined by physicians other than psychiatry. RESULTS: A total of 88% of elderly depressed inpatients had two or more comorbid physical illnesses. The most commonly prescribed psychotropics were: antidepressants (71.4%), anxiolytics (62.6%) and hypnotics (51.4%). Psychiatrists had a higher rate of prescribing psychotropics, except anxiolytics, than non-psychiatrists. Although selective serotonin reuptake inhibitors were commonly prescribed, non psychiatrists preferred the use of tricyclic antidepressants and moclobemide. Trazodone was the most preferred antidepressant, but was generally used in low dosages. CONCLUSION: Psychiatrists generally utilised higher dosages of newer antidepressants than non-psychiatrists. Differences in the prescribing pattern of psychotropics existed between physician specialties. Further investigations are warranted to determine how the selection and dosing of drugs influence the outcome of depression on the elderly. PMID- 26899463 TI - Corrigendum. PMID- 26899462 TI - Synthesis and biological evaluation of novel hydrogen sulfide releasing glycyrrhetic acid derivatives. AB - A series of hybrids, which are composed of glycyrrhetic acid (GA) and slowly hydrogen sulfide-releasing donor ADT-OH, were designed and synthesized to develop anticancer and anti-inflammatory agents. Most of the compounds, whose inhibitory rates were comparable to or higher than those of GA and aspirin, respectively, significantly inhibited xylene-induced ear edema in mice. Especially, compound V4 exhibited the most potent inhibitory rate of 60.7%. Furthermore, preliminary structure-activity relationship studies demonstrated that 3-substituted GA derivatives had stronger anti-inflammatory activities than the corresponding 3 unsubstituted GA derivatives. In addition, anti-proliferative activities of compounds V1-9 were evaluated in three different human cancer cell lines. Compound V4 showed the most high potency against all three tumor cell lines with IC50 values ranging from 10.01 MUM in Hep G2 cells to 17.8 MUM in MDA-MB-231 cells, which were superior to positive GA. PMID- 26899464 TI - Needle electromyography findings in patients with MATR3 mutation - A prospective study. PMID- 26899465 TI - Idiopathic Cervical Hematomyelia in an Infant: Spinal Cord Injury without Radiographic Abnormality Caused by a Trivial Trauma? Case Report and Review of the Literature. AB - BACKGROUND: Spontaneous or idiopathic intramedullary bleeding is a very rare event in pediatric patients. This diagnosis requires an extended clinical, laboratory, and radiologic work-up to rule out all potential causes of hematomyelia. However, children may present with hematomyelia or spinal cord injury without radiographic abnormality even after a minor trauma. CASE DESCRIPTION: A 15-month-old girl presented with a 24-hour history of progressive neurologic deficits. A trivial trauma had occurred a few days before the clinical onset. Head computed tomography scan and craniospinal magnetic resonance imaging revealed an isolated hemorrhagic central medullary lesion extending from the obex to C3 level. No underlying causes of intramedullary bleeding were identified. In the absence of obvious vascular abnormalities, the patient underwent an urgent occipitocervical decompression with hematoma evacuation. Postoperatively, the patient's motor symptoms rapidly resolved, and she was discharged with cervical collar immobilization. CONCLUSIONS: We discuss the differential diagnosis of intramedullary bleeding in children, focusing on the diagnostic protocol and therapeutic options in this age group. PMID- 26899466 TI - Dural Arteriovenous Fistula Could Be Due to Hemodynamic Disturbance in Dural Physiological Shunts? Histopathological Study and a Case Report. AB - BACKGROUND: Histopathologic studies of dural arteriovenous fistulas (dAVFs) are important for clarifying the pathogenesis. We present a case of Cognard type IV dAVF with detailed histopathologic studies in correlation with radiologic and intraoperative findings. CASE DESCRIPTION: An otherwise asymptomatic 53-year-old man presented with chronic headache. Neurologic examination revealed no abnormalities. Neuroimaging and cerebral catheter angiographic studies disclosed a left frontoparietal dAVF close to the middle third of the superior sagittal sinus, fed by the left superficial temporal and bilateral middle meningeal arteries and draining into ectatic cortical and dural veins. No evidence of superior sagittal sinus thrombosis or occlusion was seen. Intraoperatively, the parietal branch of the left superficial temporal artery penetrated the skull vault to feed the fistula; arterialized cortical and draining dural veins were also noted. Complete obliteration of the dAVF with removal of the affected dura mater was achieved safely. Histopathologic studies in serial sections documented a shunt point between the dural artery and the dural vein within the dura mater and a draining point between the dural and cortical veins. CONCLUSIONS: On the basis of clinical, angiographic, intraoperative, and histologic findings in our case, we strongly excluded acquired etiologies. PMID- 26899467 TI - Endoscopic Endonasal Management of Olfactory Neuroblastoma: A Retrospective Analysis of 10 Patients with Quality-of-Life Measures. AB - OBJECTIVE: Anterior craniofacial resection has served as the traditional surgical treatment of olfactory neuroblastoma (ON). With the development of extended endonasal approaches, the opportunity exists for using minimal access techniques for management of select tumors. This study assesses the impact of endoscopic resection on ON and patient outcomes and quality of life. METHODS: A retrospective review identified 10 patients with ON (3 women, 7 men; mean age 49.1 years) who underwent endoscopic resection during the period 2010-2013. Modified Kadish staging divided the cohort into 3 stage B patients (30%), 5 stage C patients (50%), and 2 stage D patients (20%). Outcome measures included extent of resection, complications, recurrence, and preoperative and postoperative Sino Nasal Outcome Test-20 scores. RESULTS: Gross total resection was achieved in all patients, with negative margins in 9 patients. One patient had negative frozen section pathology but was noted to have a positive posterior dural margin on final pathology. There was a 20% complication rate (pneumocephalus, ethmoid meningoencephalocele). Neoadjuvant chemotherapy and radiation were performed in 2 patients (Kadish stage C and D). Adjuvant chemotherapy and radiation were performed in 5 patients (4 Kadish stage C and 1 stage D). Postoperative radiation alone was administered in 3 patients (Kadish stage B). Analysis of postoperative Sino-Nasal Outcome Test-20 scores demonstrated no significant change relative to preoperative Sino-Nasal Outcome Test-20 scores. At the most recent follow-up examination, there was no evidence of recurrent disease in patients who underwent endoscopic resection. One patient (Kadish stage D) died during the follow-up period. Mean follow-up duration was 21.1 months. CONCLUSIONS: This series adds to the growing body of literature that suggests equivalent or improved outcomes of purely endonasal resection for select patients. Given the advanced Kadish stage of most of our patients, longer follow-up is required to determine the full applicability of purely endoscopic approaches to the treatment of ON. PMID- 26899468 TI - Integration of conductive reduced graphene oxide into microstructured optical fibres for optoelectronics applications. AB - Integration of conductive materials into optical fibres can largely expand functions of fibre devices including surface plasmon resonator/metamaterial, modulators/detectors, or biosensors. Some early attempts have been made to incorporate metals such as tin into fibres during the fibre drawing process. Due to the restricted range of materials that have compatible melting temperatures with that of silica glass, the methods to incorporate metals along the length of the fibres are very challenging. Moreover, metals are nontransparent with strong light absorption, which causes high fibre loss. This article demonstrates a novel but simple method for creating transparent conductive reduced graphene oxide film onto microstructured silica fibres for potential optoelectronic applications. The strongly confined evanescent field of the suspended core fibres with only 2 MUW average power was creatively used to transform graphene oxide into reduced graphene oxide with negligible additional loss. Existence of reduced graphene oxide was confirmed by their characteristic Raman signals, shifting of their fluorescence peaks as well as largely decreased resistance of the bulk GO film after laser beam exposure. PMID- 26899469 TI - Inhibition of DNA methyltransferase or histone deacetylase protects retinal pigment epithelial cells from DNA damage induced by oxidative stress by the stimulation of antioxidant enzymes. AB - Epigenetic modifications influence DNA damage response (DDR). In this study we explored the role of DNA methylation and histone acetylation in DDR in cells challenged with acute or chronic oxidative stress. We used retinal pigment epithelial cells (ARPE-19), which natively are exposed to oxidative stress due to permanent exposure to light and high blood flow. We employed a DNA methyltransferase inhibitor - RG108 (RG), or a histone deacetylase inhibitor - valproic acid (VA). ARPE-19 cells were exposed to tert-butyl hydroperoxide, an acute oxidative stress inducer, or glucose oxidase, which slowly liberates low doses of hydrogen peroxide in the presence of glucose, creating chronic conditions. VA and RG reduced level of intracellular reactive oxygen species and DNA damage in ARPE-19 cells in normal condition and in oxidative stress. This protective effect of VA and RG was associated with the up-regulated expression of antioxidant enzyme genes: CAT, GPx1, GPx4, SOD1 and SOD2. RG decreased the number of cells in G2/M checkpoint in response to chronic oxidative stress. Neither RG nor VA changed the DNA repair or apoptosis induced by oxidative stress. Therefore, certain epigenetic manipulations may protect ARPE-19 cells from detrimental effects of oxidative stress by modulation of antioxidative enzyme gene expression, which may be further explored in pharmacological studies on oxidative stress-related eye diseases. PMID- 26899470 TI - Spectroscopic, Structural, and Computational Characterization of Three Bispidinone Derivatives, as Ligands for Enantioselective Metal Catalyzed Reactions. AB - Three chiral derivatives of the alkaloid sparteine (bispidines), characterized by the 3,7-diazabicyclo[3.3.1]nonane moiety, were designed as efficient ligands in a number of enantioselective reactions due to their metal coordination properties. A full evaluation of the 3D properties of the compounds was carried out, as the geometrical features of the bicyclic framework are strictly related to the efficiency of the ligands in the asymmetric catalysis. The selected molecules have different molecular complexity for investigating the effects of different chiral groups on the bicycle conformation. We report here a thorough analysis of their molecular arrangement, by NMR spectroscopy, single crystal X-ray crystallography, and computational techniques, which put in evidence their conformational preferences and the parameters needed for the design of more efficient ligands in asymmetric synthetic routes. The results confirmed the high molecular flexibility of the compounds, and indicated how to achieve a control of the chair-chair/boat-chair conformational ratio, by adjusting the relative size of the substituents on the piperidine nitrogens. PMID- 26899472 TI - Clinical trials for personalized glioblastoma radiotherapy: Markers for efficacy and late toxicity but often delayed treatment - Does that matter? PMID- 26899471 TI - Glasgow Prognostic Score may be a prognostic index for overall and perioperative survival in gastric cancer without perioperative treatment. AB - BACKGROUND: Systemic inflammation is a key factor in tumor growth. C-reactive protein and albumin are parameters of systemic inflammation from the Glasgow Prognostic Score (GPS). The purpose was to evaluate the prognostic role of GPS in a homogeneous population of gastric cancer patients undergoing surgical treatment only. METHODS: Patients underwent operations between 2009 and 2014. Those who had received perioperative treatment or had other malignancies or inflammatory diseases were excluded. Eighty-eight patients met all inclusion criteria (age >18 years, documented preoperative serum levels of albumin and C-reactive protein, histologically proven gastric cancer, curative operation, including lymphadenectomy). C-reactive protein and albumin levels were retrieved from our prospective database. GPS was correlated with clinicopathologic characteristics and outcome. RESULTS: Increasing GPS was linked to aggressive tumor biology in terms of tumor size (GPS 0: 51.2% T1 and T2, 48.8% T3 and T4; GPS 1: 23.8% T1 and T2, 76.2% T3 and T4; GPS 2: 23.1% T1 and T2, 76.9% T3 and T4; P = .026), synchronous distant metastases (GPS 0: 47.1% M0, 0.0% M1; GPS 1: 25.9% M0, 0.0% M1; GPS 2: 27.1% M0, 100.0% M1; P = .030), venous vessel invasion (GPS 0: 91.2% V0, 8.8% V1; GPS 1: 66.7% V0, 33.3% V1; GPS 2: 55.0% V0, 45.0% V1; P = .008), resection margin status (GPS 0: 97.4% R0, 2.6% R1; GPS 1: 90.0% R0, 10.0% R1; GPS 2: 77.3% R0, 22.7% R1; P = .044), reduced overall survival (GPS 0: median 25.2 months [range 0.4-106.0]; GPS 1: 15.3 [0.2-59.5]; GPS 2: 5.8 [0.1-55.3]; P = .016) with median overall survival in the whole cohort being 16.2 months (range 0.1-106.0) and perioperative mortality (GPS 0: 0.0% of perioperative deaths, GPS 1: 20.0%, GPS 2: 80.0%; P = .036). Furthermore, GPS was identified as an independent prognosticator of overall survival (P = .033). A gradual decrease in survival between GPS subgroups was evident. CONCLUSION: GPS represents an independent prognostic factor for long-term outcome in resected gastric cancer patients without perioperative treatment and is strongly associated with perioperative mortality. PMID- 26899473 TI - Reactive oxygen species regulate leaf pulvinus abscission zone cell separation in response to water-deficit stress in cassava. AB - Cassava (Manihot esculenta Crantz) plant resists water-deficit stress by shedding leaves leading to adaptive water-deficit condition. Transcriptomic, physiological, cellular, molecular, metabolic, and transgenic methods were used to study the mechanism of cassava abscission zone (AZ) cell separation under water-deficit stress. Microscopic observation indicated that AZ cell separation initiated at the later stages during water-deficit stress. Transcriptome profiling of AZ suggested that differential expression genes of AZ under stress mainly participate in reactive oxygen species (ROS) pathway. The key genes involved in hydrogen peroxide biosynthesis and metabolism showed significantly higher expression levels in AZ than non-separating tissues adjacent to the AZ under stress. Significantly higher levels of hydrogen peroxide correlated with hydrogen peroxide biosynthesis related genes and AZ cell separation was detected by microscopic observation, colorimetric detection and GC-MS analyses under stress. Co-overexpression of the ROS-scavenging proteins SOD and CAT1 in cassava decreased the levels of hydrogen peroxide in AZ under water-deficit stress. The cell separation of the pulvinus AZ also delayed in co-overexpression of the ROS scavenging proteins SOD and CAT1 plants both in vitro and at the plant level. Together, the results indicated that ROS play an important regulatory role in the process of cassava leaf abscission under water-deficit stress. PMID- 26899474 TI - Arginine side chain interactions and the role of arginine as a gating charge carrier in voltage sensitive ion channels. AB - Gating charges in voltage-sensing domains (VSD) of voltage-sensitive ion channels and enzymes are carried on arginine side chains rather than lysine. This arginine preference may result from the unique hydration properties of the side chain guanidinium group which facilitates its movement through a hydrophobic plug that seals the center of the VSD, as suggested by molecular dynamics simulations. To test for side chain interactions implicit in this model we inspected interactions of the side chains of arginine and lysine with each of the 19 non-glycine amino acids in proteins in the protein data bank. The arginine guanidinium interacts with non-polar aromatic and aliphatic side chains above and below the guanidinium plane while hydrogen bonding with polar side chains is restricted to in-plane positions. In contrast, non-polar side chains interact largely with the aliphatic part of the lysine side chain. The hydration properties of arginine and lysine are strongly reflected in their respective interactions with non-polar and polar side chains as observed in protein structures and in molecular dynamics simulations, and likely underlie the preference for arginine as a mobile charge carrier in VSD. PMID- 26899476 TI - Comparing Local Infiltration and Continuous Femoral Nerve Block for Pain Relief After Total Knee Arthroplasty. PMID- 26899475 TI - Perceived social support, hopefulness, and emotional regulations as mediators of the relationship between enacted stigma and post-traumatic growth among children affected by parental HIV/AIDS in rural China. AB - Some previous studies have revealed a negative impact of enacted stigma on post traumatic growth (PTG) of children affected by HIV/AIDS, but little is known about protective psychological factors that can mitigate the effect of enacted stigma on children's PTG. This study aims to examine the mediating effects of perceived social support, hopefulness, and emotional regulation on the relationship between enacted stigma and PTG among HIV-affected children. Cross sectional data were collected from 790 children affected by parental HIV (382 girls, 408 boys) aged 6-17 years in 2012 in rural central China. Multiple regression was conducted to test the mediation model. The study found that the experience of enacted stigma had a negative effect on PTG among children affected by HIV/AIDS. Emotional regulation together with hopefulness and perceived social support mediated the impact of enacted stigma on PTG. Perceived social support, hopefulness, and emotional regulation offer multiple levels of protection that can mitigate the impact of enacted stigma on PTG. Results suggest that future psychological intervention programs should seek strategies to reduce the stigmatizing experience of these children and promote children's level of PTG, and health professionals should also emphasize the development of these protective psychological factors. PMID- 26899477 TI - Total Joint Arthroplasty in Patients Taking Methadone or Buprenorphine/Naloxone Preoperatively for Prior Heroin Addiction: A Prospective Matched Cohort Study. AB - BACKGROUND: Preoperative narcotic use has been associated with poor outcomes after total joint arthroplasty (TJA). The purpose of this study is to compare clinical outcomes of patients undergoing elective TJA while concurrently being treated with methadone or buprenorphine/naloxone for prior heroin addiction to a matched control group. METHODS: From an electronic medical record, we collected age, gender, body mass index, the presence of back pain, smoking status, history of alcohol abuse, preoperative use of a pain clinic, and use of antipsychotics, antidepressants, or systemic corticosteroids. Validated outcome measures including the 12-Item Short Form Survey, Knee Society Score (KSS), and Harris Hip Score were used to assess functional outcomes preoperatively and postoperatively. Perioperative data were retrospectively obtained from patient charts. Postoperative functional outcomes were prospectively collected at follow-up visits. Subjects were matched to 2:1 control group on the basis of procedure, sex, diagnosis, age (+/-5 years), and body mass index (+/-5 kg/m(2)). Average follow-up was 27.2 months. RESULTS: Significant preoperative differences between the groups included mean morphine-equivalent requirements (997.1 mg for study group vs 24.8 mg for controls), 12-Item Short Form Survey Mental Component Scores (MCS-12; 37.8 for study group vs 49.0 for controls), smoking history, and antipsychotic medication use. Perioperative referral to inpatient Acute Pain Service and mean in-hospital morphine-equivalent narcotic usage (793 mg/24 h for study group vs 109 mg/24 h for controls) also significantly differed between groups. Knee range of motion differed significantly between the cohorts at 1 year (77.5 for study group vs 109.4); however, no significant difference in KSS pain (87.6 vs 84.4), KSS function (61 vs 80.9), Harris Hip Score (89.2 vs 85.3), MCS 12 (47.1 vs 52.9), or complications was observed. CONCLUSION: Equivalent pain control and successful clinical outcome at 1 year can be achieved in patients who use methadone or buprenorphine/naloxone preoperatively. PMID- 26899479 TI - Denosumab: An Alternative Therapy for the Management of Giant Cell Lesions. PMID- 26899480 TI - Condylar Erosion in Patients With Chronic Temporomandibular Joint Arthralgia: A Cone-Beam Computed Tomography Study. AB - PURPOSE: The objective of this study was to assess the association between temporomandibular joint (TMJ) condylar erosion and chronic TMJ arthralgia. MATERIALS AND METHODS: Based on a sample size estimation, this case-and-control study involved 198 patients 16 to 73 years old recruited from a routine clinical practice (99 cases, patients with chronic TMJ arthralgia and mean pain duration of 16.4 months; 99 controls, asymptomatic patients without a history of orofacial pain). The clinical diagnosis of arthralgia was made according to the Research Diagnostic Criteria for Temporomandibular Disorders. Cone-beam computed tomographic (CBCT) images were evaluated for the presence or absence of erosive osseous changes of the TMJ condyle. Severity of TMJ condylar erosion was classified as grade 0 (absence of erosion), grade I (slight erosion), grade II (moderate erosion), or grade III (extensive erosion). Logistic regression analysis was used to assess the association between chronic TMJ arthralgia and condylar erosion, adjusting for age, gender, number of missing posterior teeth, and number of dental quadrants with missing posterior teeth. RESULTS: TMJ condylar erosion was found in 59.6% of cases and 21.2% of controls. There was a significant association between TMJ arthralgia and degree of condylar erosion (P < .001). The odds ratio that a TMJ with condylar erosion grade II might belong to the TMJ arthralgia group was strong (3.1:1; 95% confidence interval [CI], 1.17 to 8.09) and significant (P = .023). Significant increases in risk of TMJ arthralgia occurred with condylar erosion grade III (7.7:1; 95% CI, 3.09 to 19.18; P < .001). CONCLUSIONS: The study provides evidence of an association between TMJ condylar erosion and chronic TMJ arthralgia. PMID- 26899478 TI - Autotransplantation of Premolars With a 3-Dimensional Printed Titanium Replica of the Donor Tooth Functioning as a Surgical Guide: Proof of Concept. AB - PURPOSE: Autotransplantation of premolars is a good treatment option for young patients who have missing teeth. This study evaluated the use of a preoperatively 3-dimensional (3D)-printed replica of the donor tooth that functions as a surgical guide during autotransplantation. MATERIALS AND METHODS: Five consecutive procedures were prospectively observed. Transplantations of maxillary premolars with optimal root development were included in this study. A 3D-printed replica of the donor tooth was used to prepare a precisely fitting new alveolus at the recipient site before extracting the donor tooth. Procedure time, extra alveolar time, and number of attempts needed to achieve a good fit of the donor tooth in the new alveolus were recorded. RESULTS: For each transplantation procedure, the surgical time was shorter than 30 minutes. An immediate good fit of the donor tooth in the new alveolus was achieved with an extra-alveolar time shorter than 1 minute for all transplantations. CONCLUSION: These results show that the extra-alveolar time is very short when the surgical guide is used; therefore, the chance of iatrogenic damage to the donor tooth is minimized. The use of a replica of the donor tooth makes the autotransplantation procedure easier for the surgeon and facilitates optimal placement of the transplant. PMID- 26899481 TI - Bird and ant synergy increases the seed dispersal effectiveness of an ornithochoric shrub. AB - Seed dispersal may involve different vectors of dispersal in two or more sequential phases (i.e., diplochory). However, contributions of each phase to the overall seed dispersal effectiveness (SDE) are poorly understood and hard to evaluate due to post-dispersal processes that affect seed and seedling survival. We investigated the simultaneous bird (phase 1, in plant canopy) and ant (phase 2, on the floor) contributions to SDE with the ornithochoric shrub Erythroxylum ambiguum in a Brazilian Atlantic forest. Twelve species of birds fed on fruit and dispersed approximately 26 % of the seed crop. The remaining seed crop, 90 % of which contained viable seeds, fell to the ground beneath the parental plant. Ants either cleaned seeds in fruits or carried fallen fruit and seeds from bird feces to their nests. Although E. ambiguum has no adaptation for ant dispersal, ants were as quantitatively important as birds. Birds and ants equally increased germination rates compared to controls. However, birds deposited seeds farther from the parent, where seedling survival was higher (78 %) than it was beneath the parent (44 %), whereas ants carried seeds to their nests, where seedling survival was higher (83 %) than in controls away from their nests (63 %). Diplochory allowed a 42 % increase in SDE compared to dispersal in phase 1 alone. High lipid content in the fruit pulp of E. ambiguum may facilitate the inclusion of ants in a second step of dispersal after diaspores reach the floor. Ants can also buffer the dispersal of diplochorous plants against decreases in phase 1 dispersers. PMID- 26899482 TI - TOM1L1 drives membrane delivery of MT1-MMP to promote ERBB2-induced breast cancer cell invasion. AB - ERBB2 overexpression in human breast cancer leads to invasive carcinoma but the mechanism is not clearly understood. Here we report that TOM1L1 is co-amplified with ERBB2 and defines a subgroup of HER2(+)/ER(+) tumours with early metastatic relapse. TOM1L1 encodes a GAT domain-containing trafficking protein and is a SRC substrate that negatively regulates tyrosine kinase signalling. We demonstrate that TOM1L1 upregulation enhances the invasiveness of ERBB2-transformed cells. This pro-tumoural function does not involve SRC, but implicates membrane-bound membrane-type 1 MMP (MT1-MMP)-dependent activation of invadopodia, membrane protrusions specialized in extracellular matrix degradation. Mechanistically, ERBB2 elicits the indirect phosphorylation of TOM1L1 on Ser321. The phosphorylation event promotes GAT-dependent association of TOM1L1 with the sorting protein TOLLIP and trafficking of the metalloprotease MT1-MMP from endocytic compartments to invadopodia for tumour cell invasion. Collectively, these results show that TOM1L1 is an important element of an ERBB2-driven proteolytic invasive programme and that TOM1L1 amplification potentially enhances the metastatic progression of ERBB2-positive breast cancers. PMID- 26899483 TI - Displaced intra-articular calcaneal fractures: is there a consensus on treatment in Germany? AB - INTRODUCTION: Open reduction in displaced intra-articular calcaneal fractures entails a high rate of wound healing deficits and infections as well as an uncertain outcome, which leads to remaining ambiguity in treatment preferences. METHODS: Between January and July 2011, we emailed 575 German chairpersons of trauma and/or orthopaedic departments, asking them to complete a 31-question web based survey regarding three broad domains: fracture classification, surgical treatment algorithms and risk factors for wound healing deficits. RESULTS: The response rate was 47 %. With an incidence of 77 %, open reduction via an extended lateral approach and plate fixation was the main treatment option for displaced intra-articular fractures of the joint-depression-type (Sanders II or III). Percutaneous techniques were only preferred in individual cases, with mainly precarious wound situations (59 %) as well as in patients with a reduced general health condition (ASA 3 and 4; 41 %). The re-operation rate due to infections and wound healing deficits after an extended lateral approach was reported with a percentage of 0-5 % by 88 % of the respondents. Participants stated that especially a poor microcirculation of the foot, disregard of soft tissue conserving techniques, overall condition of the patient, smoking, long time-to surgery and operation time are the main reasons for wound healing deficits. CONCLUSION: Given the extended lateral approach as the preferred treatment option, we found minimally invasive techniques and primary arthrodesis of the lower ankle joint play a minor role in treating intra-articular calcaneal fractures in Germany. Ninety percent of our respondents stated less than 5 % of patients required re-operations due to infections and wound healing deficits. Level of Evidence Level V, expert opinion. PMID- 26899484 TI - Effect of local anaesthetic wound infiltration on acute pain and bleeding after primary total hip arthroplasty: the EDIPO randomised controlled study. AB - PURPOSE: Total hip arthroplasty (THA) is considered a painful procedure with significant blood loss. The aim of the this study was to determine whether local infiltration analgaesia (LIA) (with long-acting local anaesthetics and epinephrine) during THA could reduce acute postoperative pain, improve early recovery and reduce per- and postoperative bleeding. METHODS: One hundred and fifty patients scheduled for primary THA were randomised into two groups. The treatment group received LIA (ropivacaine with epinephrine), whereas the control group had no infiltration. Pain intensity was measured with a visual analogue scale (VAS) for the duration of hospital stay and analgaesic consumption. Length of hospital stay, time to get out of bed alone and the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index at 3, 6 and 12 months were recorded to evaluate recovery. Per- and postoperative bleeding were evaluated using direct and indirect criteria (operative blood loss, haemoglobin, estimation of uncompensated blood loss and red blood cell transfusion). RESULTS: Patients with LIA had significantly less pain during the first 24 h (p = 0.04). No significant differences were found in terms of analgaesic consumption (p = 0.57), early and delayed recovery or bleeding between groups. CONCLUSIONS: Operative wound infiltration of LIA reduced acute pain after primary THA but did not improve recovery or influence per- and postoperative bleeding. PMID- 26899485 TI - Trends in primary and revision knee arthroplasty among orthopaedic surgeons who take the American Board of Orthopaedics part II exam. AB - PURPOSE: A certified list of all operative cases performed within a six month period is required of surgeons by the American Board of Orthopaedic Surgery (ABOS) as a prerequisite to taking the Part II Oral Examination. Using the data on these cases collected and maintained by ABOS, this study assessed the influence of prior fellowship training in adult reconstruction on the volume and surgeon-reported complication rate of knee joint arthroplasty cases over time. METHODS: All data were self reported to a secure Internet database (SCRIBE) by candidates who applied to take Part II of the ABOS Examination for the first time. This database was searched for all procedures done between 2003 and 2013 with CPT codes for total and revision knee arthroplasty and removal of knee implant (static or dynamic spacer) to determine procedural volumes and early complication rates among Board-eligible orthopaedic surgeons with and without adult reconstructive fellowship training. RESULTS: More than 43,000 knee arthroplasty surgeries were identified. Surgeons who had completed adult reconstruction fellowship training after residency performed 55 % of total knee arthroplasties, averaging 33.5 knee arthroplasties during the six month case collection period compared to 7.4 procedures by non-fellowship-trained surgeons (p < 0.001). Adult reconstruction fellowship-trained surgeons performed significantly more revisions for infection (average 6.6 versus 2.2 revisions) (p < 0.001). Adult reconstruction fellowship training did not significantly affect complication rates for primary arthroplasty but was associated with an increased complication rate for revisions. Those surgeons who performed more than 100 arthroplasties a year reported significantly fewer complications in primary arthroplasties (12.7 % versus 16.9 %) (p < 0.001). Over time, an increasing percentage of arthroplasties were done by surgeons with adult reconstruction fellowship training. CONCLUSIONS: Adult reconstruction fellowship-trained surgeons performed an increasing number of primary and more complex knee arthroplasties from 2003 to 2013. Surgeons who perform a larger volume of knee arthroplasty surgeries report fewer early complications than surgeons with fewer cases. LEVEL OF EVIDENCE: 4. PMID- 26899487 TI - Association between amount of sleep, daytime sleepiness and health-related quality of life in schoolchildren. AB - AIMS: To analyse the association between amount of sleep and daytime sleepiness and health-related quality of life in schoolchildren during adolescence and to study the effect of age on this association. BACKGROUND: Sufficient sleep is essential for the health of children and adolescents. Sleep influences almost all dimensions of life. DESIGN: A 5-year prospective follow-up study (2004-2010) following 568 Finnish schoolchildren aged between 10-15. METHODS: The amount of sleep and perceived daytime sleepiness were assessed by a special questionnaire added to The Health Behaviour in School-aged Children questionnaire. The Finnish version of the Paediatric Quality of Life Inventory was used to assess health related quality of life. The data were collected in 2004, 2006 and 2009/2010. Data were analysed with hierarchical linear mixed models. RESULTS/FINDINGS: The more daytime sleepiness occurred, the lower the health-related quality of life was and similar linear association was seen in every age group. The amount of sleep was significantly positively linearly associated with health-related quality of life but not persistent across age groups. Positive association was significant at 15 years of age but not at other age groups. Similar linear association between daytime sleepiness and school-related sub scores was also found. CONCLUSION: Sufficient sleep is essential for health-related quality of life and should be protected and measured in the school health service. PMID- 26899488 TI - Prognostic role of Gli1 expression in solid malignancies: a meta-analysis. AB - Gli1 is a downstream transcriptional factor of Sonic hedgehog pathway in mammalians, and has been recognized as a proliferative indicator of carcinogenesis. However, its actual role in prognosis among solid malignancies remains unclear. Therefore we performed this meta-analysis aiming to discover the correlation between Gli1 positivity and clinical prognosis in patients suffering from diverse carcinomas. A total of 39 studies containing 4496 cases were selected into our quantitative analysis via electronic database search. Original data of 3-year, 5-year, 10-year overall survival and disease-free survival were extracted and calculated using odds ratio and Mantel-Haenszel model. Subgroup analysis was also conducted to clarify the possible confounding factors. P < 0.05 was considered significant in statistics. Gli1 redundancy was associated with worse 3-year, 5-year, 10-year overall survival and disease-free survival in solid malignancies. Different source regions, sample-size, mean-age and detection approaches had no impact on the negative prognostic effect of Gli1 over expression. Nevertheless, stratified by cancer type and subcellular localization, cytoplasmic Gli1 expression and Gli1 positivity in intracranial tumors was not correlated to poorer 3-year and 5-year prognosis. The over-expression of Gli1 is a credible indicator of poorer prognosis in most of solid malignancies, irrespective of intracranial tumors. PMID- 26899489 TI - Meta-Analysis of Effects of Bivalirudin Versus Heparin on Myocardial Ischemic and Bleeding Outcomes After Percutaneous Coronary Intervention. AB - Bivalirudin is an alternative to unfractionated heparin (UFH) anticoagulation during percutaneous coronary intervention. Previously, we have reported clinical benefit on major bleeding in favor of bivalirudin compared with UFH monotherapy but inconclusive results on mortality. Controversial data have been reported in the last 2 years. We conducted an updated meta-analysis including randomized trials and observational studies, which evaluated ischemic and bleeding outcomes for bivalirudin compared with UFH-only during percutaneous coronary intervention. We included 18 observational studies and 12 randomized trials published from 2003 to 2015. Primary outcomes were major adverse cardiovascular events within 30 days including death, myocardial infarction, and urgent revascularization and stent thrombosis, major bleeding, and transfusion. Overall, we found a significant risk reduction with bivalirudin for major bleeding (odds ratio [OR] 0.59, 95% confidence interval [CI] 0.49 to 0.71, p <0.0001) and for transfusion (OR 0.79, 95% CI 0.66 to 0.95, p = 0.01) and similar risk for major adverse cardiovascular events (OR 0.98, 95% CI 0.86 to 1.12, p = 0.80). However, there was a substantial increased risk of stent thrombosis associated with bivalirudin (OR 1.52, 95% CI 1.11 to 2.08, p = 0.009). No impact on mortality was found. Meta-regression analyses on major bleeding suggested that bivalirudin was more effective than UFH at doses >60 IU/kg and independent of radial access. In conclusion, compared with UFH monotherapy, bivalirudin remains associated with less bleeding risk but higher stent thrombosis risk. Further study remains required to define its role in current antithrombotic armamentarium. PMID- 26899491 TI - Cost Savings Associated With Implementation of Peer-Reviewed Appropriate Use Criteria for Percutaneous Coronary Interventions. AB - Appropriate use criteria (AUC) for coronary revascularization have been developed to provide a practical standard to assess the quality of patient selection for percutaneous coronary interventions (PCI). However, the economic impact of AUC implementation has yet to be quantified. A peer-reviewed AUC process was implemented at UnityPoint Trinity in February 2012. Volumes of PCI cases were measured in 12-month intervals for 2 years after AUC implementation and compared with volumes from the corresponding 12-month intervals in the 2 years preceding implementation of AUC. Hospital reimbursement was averaged based on each year's payer mix and reimbursement contracts. In the 2 years preceding AUC implementation, PCI volumes were similar (1,414 in 2010 and 1,411 in 2011). After AUC implementation, volumes of PCI decreased by 17% in both 2012 and 2013. From 2012 to 2013, the relative ratio of elective to acute interventions decreased from 1.36 to 1.02. In the same time frame, the proportion of appropriate PCI significantly increased from 76% to 84% (p <0.001). Total hospital reimbursement for PCI decreased by 36% after AUC implementation. In conclusion, implementation of a peer-reviewed AUC process at the UnityPoint Trinity led to significant cost savings through a large decrease in volume of PCI with concurrent improvement in PCI appropriateness. PMID- 26899490 TI - Comparison of Causes of Death After Heart Transplantation in Patients With Left Ventricular Ejection Fractions <=35% Versus >35. AB - Sudden cardiac death (SCD) is a common cause of death in the general population, occurring in 300,000 to 350,000 people in the United States alone. Currently, there are no data supporting implantable cardioverter-defibrillator therapy in patients who underwent orthotopic heart transplant (OHT) with low left ventricular ejection fraction (LVEF). In this retrospective study, we included all patients who underwent primary OHT at our institution from 2007 to 2013. We compared the cause of death in patients who underwent OHT and evaluated the correlation of the cause of death and the patients' LVEF. Our objectives were to determine whether patients who underwent OHT with LVEF <35% are at increased risk for SCD compared with those who underwent OHT with normal LVEF. To summarize our results, a total of 345 patients were included in our study (mean age 50 +/- 14 years, 68% men). The mean follow-up was 1,260 +/- 698 days. Forty patients (11.5%) died >6 months after OHT. Surviving patients had higher LVEF compared with deceased patients (64 +/- 7% and 50 +/- 24%, respectively, p <=0.001). In all, 10 (25%) of the deceased patients died suddenly, 9 (23%) from sepsis, and 8 (20%) from malignancy. Of the 11 deceased patients with LVEF <=35%, 2 patients (18%) died suddenly compared with 9 SCDs among the 29 deceased patients (31%) with LVEF >35% (p = 0.54). In conclusion, patients who underwent OHT who died were more likely to have LVEF <35%, and a quarter of the deceased patients who underwent OHT died suddenly. A reduced LVEF was not associated with an increased risk of SCD. PMID- 26899492 TI - Comparisons of Clinical and Procedural Outcomes Between Transradial and Transfemoral Approaches in Percutaneous Coronary Intervention (from the Korean Transradial Intervention Prospective Registry). AB - As few studies have reported the impact of transradial interventions (TRIs) versus transfemoral interventions (TFIs) on percutaneous coronary interventions using real-world registry data, we compared the clinical and procedural outcomes between TRIs and TFIs in the Korean Transradial Intervention Prospective Registry. Patients undergoing percutaneous coronary interventions were consecutively registered from February 2014 to July 2014 in this multicenter registry. Composite events were evaluated for all-cause deaths, nonfatal myocardial infarctions, and repeat revascularizations within 30 days. Nonlesion complications included access site complications and bleeding events. A total of 1,225 patients (232 for TFIs and 993 for TRIs) were analyzed. All-cause deaths and composite events were more frequent in the TFI group than in the TRI group. Procedure failures and nonlesion complications were also more frequent in the TFI group, whereas lesion complication rates were similar in the 2 groups. Procedure times were not different between the 2 groups, whereas fluoroscopy times were longer and contrast volumes were larger in the TFI group. However, in a propensity score-matched cohort, all-cause deaths, composite events, procedure failures, and lesion and nonlesion complications were not different between the 2 groups. In contrast, in the matched cohort, the procedure and fluoroscopy times were longer and the contrast volumes were larger in the TFI group. In conclusion, TRI was as effective and safe as TFI in terms of short-term clinical outcomes, procedure success rates, and complication rates, whereas TRI was more effective for reducing procedure times and hazardous exposure to radiation and contrast media. PMID- 26899495 TI - A Case of a Bilateral Inflammatory Breast Cancer: A Case Report. AB - Cases of bilateral inflammatory breast cancer (IBC) are extremely rare. Our search criteria only found one other record of metachronous bilateral IBC (1). We present the case of a patient who was treated for IBC with neoadjuvant chemotherapy, modified radical mastectomy (MRM), and whole breast radiation. Less than 1 year later, the patient had a recurrence of IBC on the left chest wall with in the radiated field, as well as a new IBC on the contralateral side. Bilateral IBC is extremely rare. This entity can present challenges for the standard treatment of IBC with neoadjuvant chemotherapy, MRM, and whole breast radiation (2). Our case study shows the importance of scheduled routine imaging, screening with physical examination after IBC management, and good patient compliance in this aggressive disease (3). PMID- 26899494 TI - Gender, Race, and Health Insurance Status in Patients Undergoing Catheter Ablation for Atrial Fibrillation. AB - Catheter ablation for atrial fibrillation (AF) has emerged as a popular procedure. The purpose of this study was to examine whether there exist differences or disparities in ablation utilization across gender, socioeconomic class, insurance, or race. Using the Nationwide Inpatient Sample (2000 to 2012), we identified adults hospitalized with a principal diagnosis of AF by ICD 9 code 427.31 who had catheter ablation (ICD 9 code-37.34). We stratified patients by race, insurance status, age, gender, and hospital characteristics. A hierarchical multivariate mixed-effect model was created to identify the independent predictors of AF ablation. Among an estimated total of 3,508,122 patients (extrapolated from 20% Nationwide Inpatient Sample) hospitalized with a diagnosis of AF in the United States from the year 2000 to 2012, 102,469 patients (2.9%) underwent catheter ablations. The number of ablations was increased by 940%, from 1,439 in 2000 to 15,090 in 2012. There were significant differences according to gender, race, and health insurance status, which persisted even after adjustment for other risk factors. Female gender (0.83 [95% CI 0.79 to 0.87; p <0.001]), black (0.49 [95% CI 0.44 to 0.55; p <0.001]), and Hispanic race (0.64 [95% CI 0.56 to 0.72; p <0.001]) were associated with lower likelihoods of undergoing an AF ablation. Medicare (0.93, 0.88 to 0.98, <0.001) or Medicaid (0.67, 0.59 to 0.76, <0.001) coverage and uninsured patients (0.55, 0.49 to 0.62, <0.001) also had lower rates of AF ablation compared to patients with private insurance. In conclusion we found differences in utilization of catheter ablation for AF based on gender, race, and insurance status that persisted over time. PMID- 26899493 TI - Effect of Previous Failure on Subsequent Procedural Outcomes of Chronic Total Occlusion Percutaneous Coronary Intervention (from a Contemporary Multicenter Registry). AB - We sought to examine the impact of previous failure on the outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI). We examined the clinical and angiographic characteristics and procedural outcomes of 1,213 consecutive patients who underwent 1,232 CTO PCIs from 2012 to 2015 at 12 US centers. Mean age was 65 +/- 10 years, and 84.8% of patients were men. A previously failed attempt had been performed in 215 patients (17.5%). As compared with patients without previous CTO PCI failure, patients with previous failure had higher Multicenter CTO Registry in Japan CTO score (2.40 +/- 1.13 vs 3.28 +/- 1.29, p <0.0001) and were more likely to have in-stent restenosis (10.5% vs 28.4%, p <0.0001) and to undergo recanalization attempts using the retrograde approach (41% vs 50%, p = 0.011). Technical (90% vs 88%, p = 0.390) and procedural (89% vs 86%, p = 0.184) success were similar in the 2 study groups; however, median procedure time (125 vs 142 minutes, p = 0.026) and fluoroscopy time (45 vs 55 minutes, p = 0.015) were longer in the previous failure group. In conclusion, a previously failed CTO PCI attempt is associated with higher angiographic complexity, longer procedural duration, and fluoroscopy time, but not with the success and complication rates of subsequent CTO PCI attempts. PMID- 26899497 TI - Large Bone Vertical Augmentation Using a Three-Dimensional Printed TCP/HA Bone Graft: A Pilot Study in Dog Mandible. AB - BACKGROUND: Osteoflux is a three-dimensional printed calcium phosphate porous structure for oral bone augmentation. It is a mechanically stable scaffold with a well-defined interconnectivity and can be readily shaped to conform to the bone bed's morphology. PURPOSE: An animal experiment is reported whose aim was to assess the performance and safety of the scaffold in promoting vertical growth of cortical bone in the mandible. MATERIALS AND METHODS: Four three-dimensional blocks (10 mm length, 5 mm width, 5 mm height) were affixed to edentulous segments of the dog's mandible and covered by a collagen membrane. During bone bed preparation, particular attention was paid not to create defects 0.5 mm or more so that the real potential of the three-dimensional block in driving vertical bone growth can be assessed. Histomorphometric analyses were performed after 8 weeks. RESULTS: At 8 weeks, the three-dimensional blocks led to substantial vertical bone growth up to 4.5 mm from the bone bed. Between 0 and 1 mm in height, 44% of the surface was filled with new bone, at 1 to 3 mm it was 20% to 35%, 18% at 3 to 4, and ca. 6% beyond 4 mm. New bone was evenly distributed along in mesio-distal direction and formed a new crest contour in harmony with the natural mandibular shape. CONCLUSIONS: After two months of healing, the three-dimensional printed blocks conducted new bone growth above its natural bed, up to 4.5 mm in a canine mandibular model. Furthermore, the new bone was evenly distributed in height and density along the block. These results are very promising and need to be further evaluated by a complete powerful study using the same model. PMID- 26899496 TI - Natural thioallyl compounds increase oxidative stress resistance and lifespan in Caenorhabditis elegans by modulating SKN-1/Nrf. AB - Identification of biologically active natural compounds that promote health and longevity, and understanding how they act, will provide insights into aging and metabolism, and strategies for developing agents that prevent chronic disease. The garlic-derived thioallyl compounds S-allylcysteine (SAC) and S allylmercaptocysteine (SAMC) have been shown to have multiple biological activities. Here we show that SAC and SAMC increase lifespan and stress resistance in Caenorhabditis elegans and reduce accumulation of reactive oxygen species (ROS). These compounds do not appear to activate DAF-16 (FOXO orthologue) or mimic dietary restriction (DR) effects, but selectively induce SKN-1 (Nrf1/2/3 orthologue) targets involved in oxidative stress defense. Interestingly, their treatments do not facilitate SKN-1 nuclear accumulation, but slightly increased intracellular SKN-1 levels. Our data also indicate that thioallyl structure and the number of sulfur atoms are important for SKN-1 target induction. Our results indicate that SAC and SAMC may serve as potential agents that slow aging. PMID- 26899498 TI - A beacon of hope in stroke therapy-Blockade of pathologically activated cellular events in excitotoxic neuronal death as potential neuroprotective strategies. AB - Excitotoxicity, a pathological process caused by over-stimulation of ionotropic glutamate receptors, is a major cause of neuronal loss in acute and chronic neurological conditions such as ischaemic stroke, Alzheimer's and Huntington's diseases. Effective neuroprotective drugs to reduce excitotoxic neuronal loss in patients suffering from these neurological conditions are urgently needed. One avenue to achieve this goal is to clearly define the intracellular events mediating the neurotoxic signals originating from the over-stimulated glutamate receptors in neurons. In this review, we first focus on the key cellular events directing neuronal death but not involved in normal physiological processes in the neurotoxic signalling pathways. These events, referred to as pathologically activated events, are potential targets for the development of neuroprotectant therapeutics. Inhibitors blocking some of the known pathologically activated cellular events have been proven to be effective in reducing stroke-induced brain damage in animal models. Notable examples are inhibitors suppressing the ion channel activity of neurotoxic glutamate receptors and those disrupting interactions of specific cellular proteins occurring only in neurons undergoing excitotoxic cell death. Among them, Tat-NR2B9c and memantine are clinically effective in reducing brain damage caused by some acute and chronic neurological conditions. Our second focus is evaluation of the suitability of the other inhibitors for use as neuroprotective therapeutics. We also discuss the experimental approaches suitable for bridging our knowledge gap in our current understanding of the excitotoxic signalling mechanism in neurons and discovery of new pathologically activated cellular events as potential targets for neuroprotection. PMID- 26899499 TI - Cancer TARGETases: DSB repair as a pharmacological target. AB - Cancer is a disease attributed to the accumulation of DNA damages due to incapacitation of DNA repair pathways resulting in genomic instability and a mutator phenotype. Among the DNA lesions, double stranded breaks (DSBs) are the most toxic forms of DNA damage which may arise as a result of extrinsic DNA damaging agents or intrinsic replication stress in fast proliferating cancer cells. Accurate repair of DSBs is therefore paramount to the cell survival, and several classes of proteins such as kinases, nucleases, helicases or core recombinational proteins have pre-defined jobs in precise execution of DSB repair pathways. On one hand, the proper functioning of these proteins ensures maintenance of genomic stability in normal cells, and on the other hand results in resistance to various drugs employed in cancer therapy and therefore presents a suitable opportunity for therapeutic targeting. Higher relapse and resistance in cancer patients due to non-specific, cytotoxic therapies is an alarming situation and it is becoming more evident to employ personalized treatment based on the genetic landscape of the cancer cells. For the success of personalized treatment, it is of immense importance to identify more suitable targetable proteins in DSB repair pathways and also to explore new synthetic lethal interactions with these pathways. Here we review the various alternative approaches to target the various protein classes termed as cancer TARGETases in DSB repair pathway to obtain more beneficial and selective therapy. PMID- 26899501 TI - Regulation of brain-derived neurotrophic factor (BDNF) and its precursor proBDNF in the brain by serotonin. PMID- 26899502 TI - Intrinsic polarization control in rectangular GaN nanowire lasers. AB - We demonstrate intrinsic, linearly polarized lasing from single GaN nanowires using cross-sectional shape control. A two-step top-down fabrication approach was employed to create straight nanowires with controllable rectangular cross sections. A clear lasing threshold of 444 kW cm(-2) and a narrow spectral line width of 0.16 nm were observed under optical pumping at room temperature, indicating the onset of lasing. The polarization was along the short dimension (y direction) of the nanowire due to the higher transverse confinement factors for y polarized transverse modes resulting from the rectangular nanowire cross-section. The results show that cross-sectioned shape control can enable inherent control over the polarization of nanowire lasers without additional environment requirements, such as placement onto lossy substrates. PMID- 26899503 TI - Evaluation of combined use of the MALDI-TOF and GenomEra MRSA/SA assay for the direct detection of methicillin resistance in Staphylococcus aureus from positive blood culture bottles. PMID- 26899505 TI - Light-triggered assembly-disassembly of an ordered donor-acceptor pi-stack using a photoresponsive dimethyldihydropyrene pi-switch. AB - Self-organization of donor and acceptor pi-systems forms alternate D-A stacks of the donor and acceptor molecules. Using a photochromic pi-switch as a donor and an electron deficient acceptor dye such stacks were formed. Photomodulation of the donor unit with visible light led to a photoisomerized state having a non planar structure with reduced donor ability, thereby causing destruction of the alternate D-A pi-stacks. The formation and destruction of the stacks were studied by various spectroscopy methods. Both the stacks and the depleted stacks were studied by DLS and SEM experiments. The regeneration of the stacks occurred in solution with the reversal of the photoisomerization process with ultraviolet light. Computational and differential scanning calorimetric studies validated the thermodynamics of the formation of the stacks. This work presents a reversible assembly-disassembly of a donor-acceptor pi system devoid of additional auxiliary non-covalent bonding motifs in the donor and acceptor molecules. PMID- 26899504 TI - Predictors of and attitudes toward counseling about SUDEP and other epilepsy risk factors among Austrian, German, and Swiss neurologists and neuropediatricians. AB - OBJECTIVE: To examine the attitudes toward counseling about sudden unexpected death in epilepsy (SUDEP) and other epilepsy risk factors among Austrian, German, and Swiss neurologists and neuropediatricians, and to determine factors associated with not discussing SUDEP. METHODS: Questionnaires were sent to approximately 5,000 neurologists and neuropediatricians in 2014 regarding respondents' demographics, their working environments, and how often they discussed SUDEP, suicidal ideations on anticonvulsive medication, driving restrictions, and risks in daily life activities. RESULTS: In total, 519 surveys were completed (respondents' mean age: 45.5 years, 41.6% female, 66.9% adult neurologists, 31.0% neuropediatricians). A minority of 2.7% reported that they counseled all of their patients on SUDEP, 8.7% counseled most of the time (50 90%), 20.8% sometimes (10-49%), 44.5% rarely (1-9%), and 23.3% reported not counseling about SUDEP at all. In contrast, 92.9% reported that they counseled all patients about driving restrictions and 81.5% about risks in daily life activities. Suicidal ideations were discussed in 59.0% for some and in 3.3% for all patients, whereas 35.1% of respondents reported never discussing suicidal ideations. Independent predictors of not discussing SUDEP were no additional epilepsy training, no or uncertain SUDEP cases in the past, <10 years in practice, <25 epilepsy patients seen per quarter, and the opinion of a lack of consequences in SUDEP prevention. The opinion that SUDEP is a risk factor in particular patient groups and the attitude that all risks should be discussed predicted counseling on SUDEP. SIGNIFICANCE: Our findings show a discrepancy between guidelines and practice regarding the discussion of premature mortality due to SUDEP or suicidality. Both are not discussed at all by a substantial proportion of neurologists and neuropediatricians. This is in contrast to ubiquitous education about driving restrictions. Dissemination of knowledge among physicians about potential preventive strategies might increase the likelihood of discussion. Clinical practice guidelines are welcomed by the majority of physicians in this process. PMID- 26899507 TI - Neural oscillations in antipsychotic-naive patients with a first psychotic episode. AB - OBJECTIVES: In chronic schizophrenic psychoses, oscillatory abnormalities predominantly occur in prefrontal cortical regions and are associated with reduced communication across cortical areas. Nevertheless, it remains unclear whether similar alterations can be observed in patients with a first episode of psychosis (FEP), a state characterised by pathological features occurring in both late prodromal patients and initial phases of frank schizophrenic psychoses. METHODS: We assessed resting-state electroencephalographic data of 31 antipsychotic-naive FEP patients and 29 healthy controls (HC). We investigated the three-dimensional (3D) current source density (CSD) distribution and lagged phase synchronisation (LPS) of oscillations across small-scale and large-scale brain networks. We additionally investigated LPS relationships with clinical symptoms using linear mixed-effects models. RESULTS: Compared to HC, FEP patients demonstrated abnormal CSD distributions in frontal areas of the brain; while decreased oscillations were found in the low frequencies, an increase was reported in the high frequencies (P < 0.01). Patients also exhibited deviant LPS in the high frequencies, whose dynamics changed over increasing 3D cortico cortical distances and increasing psychotic symptoms. CONCLUSIONS: These results indicate that in addition to prefrontal cortical abnormalities, altered synchronised neural oscillations are also present, suggesting possible disruptions in cortico-cortical communications. These findings provide new insights into the pathophysiological mechanisms of emerging schizophrenic psychoses. PMID- 26899506 TI - Genetic diversity, viraemic and aminotransferases levels in chronic infected hepatitis B patients from Cameroon. AB - BACKGROUND: HBV infection annually accounts for 1 million deaths worldwide as a result of cirrhosis, liver failure, and hepatocellular carcinoma. In addition to varying responses to antiviral therapy, HBV genotypes have also been shown to be associated with different pattern of disease progression. Despite a high HBV prevalence of >8%, very few studies have been carried out in Cameroon to determine the genotype distribution across the country. The aim of this study was to determine the prevalent genotypes, level of viraemia and correlate these parameters with liver enzymes known to be the most affordable and widely used biomarkers for monitoring disease progression in Cameroon. METHODS: This was a hospital-community based study in which 81 participants who had been previously diagnosed of HBV were recruited and screened for HIV, HCV (for exclusion) and HBsAg for confirmation. Fifty known negative cases for HIV, HBV and HCV were tested and recruited to be used as healthy controls. Viral load and genotyping was performed only for HBV-mono infected cases using the Abbott RealTime HBV automated m2000 system and INNO-LiPA HBV Genotyping assay respectively. Liver enzymes were measured by spectrophotometry on both hepatitis B positive and healthy control cases. RESULTS: The mean alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were significantly higher (p < 0.001) in HBV infected patients than "healthy controls". Of the 81 HBV infected cases viral load was detected in 76 (93.8%) with mean viral load of 120,807 IU/ml +/- 440,159 SD. Mean viral load was significantly different in patients with abnormal AST and ALT when compared with patients who had normal ALT and AST. The identified genotypes in order of prevalence were A (47.4%), E (39.5%), C/E (3.9%) A/C (2.6%), A/E (2.6%), B (1.3%), A/B (1.3%) and B/C (1.3%). CONCLUSION: Genotype E was significantly associated with higher mean viral load and mean AST levels. However, aminotransferase levels may not be a good marker for HBV disease progression as some patients could have normal levels but still present with very high viral loads and therefore, remain active HBV infection with possible high transmission. PMID- 26899508 TI - Improving Neurodevelopmental Surveillance and Follow-up in Infants with Congenital Heart Disease. AB - OBJECTIVE: We hypothesize that neurodevelopmental surveillance of targeted patients with congenital heart disease during the admission for their cardiac surgery would improve neurodevelopmental assessment and outpatient follow-up rates. DESIGN: All patients under 12 months of age who were operated on between October 2013 and October 2014 and were considered at risk for neurodevelopmental delay in accordance with the 2012 American Heart Association Scientific Statement were included. A protocol was implemented to increase surveillance of targeted patients during the hospitalization for their cardiac surgery. A historical control cohort was used from a 6-month period that preceded initiation of the program from July 2012 to December 2012. Univariate analysis assessed the effects of patient demographics, anatomy, postoperative course, and distance from clinic on inpatient screening and follow-up to evaluate areas for future improvement. RESULTS: Neurodevelopmental surveillance in the post-protocol period increased from 21% to 82% (P < .001) as did compliance rates for outpatient follow-up from 38% to 52% (P < .001). Patients receiving consultation were younger (median 1.2 months range 0.3-3.1 vs. 4.0 range 1.2-5.5, P = .002), had a longer intensive care unit duration (median 8 days range 4-13 vs. 4 range 3-8, P = .044), and a longer total hospital duration (median 14 days range 8-25 vs. 8 range 6-16, P = .023). The presence of single ventricle anatomy was associated with a lower follow-up rate at 29% than those with biventricular hearts at 64% (P = .009). Distance from the clinic did not have an effect on follow-up (P = .39). CONCLUSION: The protocol described increased neurodevelopmental surveillance of high risk patients. Individuals that were younger and in the hospital longer were more likely to be successfully seen and comply with outpatient follow-up than those not receiving inpatient risk assessment. Patients with single ventricle anatomy may benefit from a modified follow-up schedule to improve compliance rates. Travel distance has no effect on likelihood of outpatient cardiac neurodevelopmental follow-up. PMID- 26899509 TI - Not by the Red on My Chinny Chin Chin: A Case of Mandibular Osteomyelitis in a 5 Year-Old Girl. AB - BACKGROUND: Osteomyelitis is not an uncommon emergency department diagnosis in pediatric patients, and most cases are in the lower extremities. Children can present with acute, subacute, or chronic erythema, pain, swelling, or decreased use of the extremity; some patients will also have fever or elevated serum inflammatory markers, or both. CASE REPORT: We present the case of a healthy 5 year-old girl who presented to the emergency department with 3 weeks of painless chin swelling and 2 days of erythema and pain. While laboratory testing was normal, magnetic resonance imaging demonstrated osteomyelitis of the mandible, later confirmed by biopsy. After 4 weeks of intravenous antibiotics and an additional 2 weeks of oral antibiotics, the patient recovered completely without any residual findings. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case demonstrates that osteomyelitis can develop in previously healthy, fully vaccinated children with competent immune systems. Systemic findings (ie, fever and elevated serum inflammatory markers) may be absent, and osteomyelitis should always be considered in the differential diagnosis for a child presenting with subacute to chronic cutaneous findings without other clear explanation. PMID- 26899510 TI - Superior Vena Cava Syndrome with Cardiac Device-related Infective Endocarditis Secondary to Pacemaker Infection. PMID- 26899500 TI - Cancer stem cells and chemoresistance: The smartest survives the raid. AB - Chemoresistant metastatic relapse of minimal residual disease plays a significant role for poor prognosis of cancer. Growing evidence supports a critical role of cancer stem cell (CSC) behind the mechanisms for this deadly disease. This review briefly introduces the basics of the conventional chemotherapies, updates the CSC theories, highlights the molecular and cellular mechanisms by which CSC smartly designs and utilizes multiple lines of self-defense to avoid being killed by chemotherapy, and concisely summarizes recent progress in studies on CSC-targeted therapies in the end, with the hope to help guide future research toward developing more effective therapeutic strategies to eradicate tumor cells in the patients. PMID- 26899511 TI - Osteoid Osteoma. PMID- 26899512 TI - Reducing a Shoulder Dislocation Without Sweating. The Davos Technique and its Results. Evaluation of a Nontraumatic, Safe, and Simple Technique for Reducing Anterior Shoulder Dislocations. AB - BACKGROUND: Anterior shoulder dislocation is a well-known injury for people working in emergency departments (EDs). Throughout the years, the focus has been shifted onto more gentle reduction techniques with less risk of iatrogenic injury, fracture displacement, and less pain for the patient. We present the results of one such technique, the Davos reduction maneuver, also known as the Boss-Holzach-Matter technique, as well as its advantages, disadvantages, and a few practical tips. DISCUSSION: We evaluated, retrospectively, 100 patients presenting with an anteroinferior shoulder dislocation, who were treated in the ED of the university hospital of Geneva, Switzerland, in a time period of 18 months. In every case, the Davos technique was used for shoulder reduction. The detailed technique is described. Successful reduction was achieved in 86 patients. There were no neurological complications. Greater tuberosity fracture malreduction was noted in one case. Eighteen patients received no analgesia. Our results were comparable or superior to other reduction techniques. CONCLUSION: We concluded that the Davos technique is an easy, nontraumatic, very well-tolerated, and most of all, safe way to reduce a shoulder. It is complication free and easy to apply, giving reproducible and comparable or superior results to other reduction techniques. At the same time, it is well tolerated by a compliant patient, which makes it an ideal first-time reduction technique for anterior shoulder dislocations. PMID- 26899514 TI - Horner's Syndrome after Scalene Block and Carotid Dissection. AB - BACKGROUND: Horner's syndrome refers to the clinical triad of ptosis, miosis, and anhidrosis resulting from disruption of the ocular and facial sympathetic pathways. A myriad of etiologies can lead to Horner's syndrome; awareness of the underlying anatomy can assist physicians in identifying potential causes and initiating appropriate care. CASE REPORT: Two patients presented to our Nashville area hospital in 2014. Patient 1 was a 26-year-old man who noticed facial asymmetry one day after an outpatient orthopedic procedure. His symptoms were attributed to his posterior interscalene anesthesia device; with deactivation of this device, the symptoms rapidly resolved. Patient 2 was a 42-year-old man who presented to our emergency department with persistent headache and ptosis over several weeks. Computed tomography angiography revealed ipsilateral carotid dissection and the patient was admitted for further management. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: The pathologies underlying Horner's syndrome are exceedingly diverse. Although classic teaching often focuses on neoplastic causes, and more specifically Pancoast tumors, neoplasms are discovered only in a small minority of Horner's syndrome cases. Other etiologies include trauma, cervical artery dissection, and infarction. With a better understanding of the pertinent anatomy and array of possible etiologies, emergency physicians may have more success in identifying and treating the causes of Horner's syndrome. PMID- 26899513 TI - Outcomes of Patients With Premature Discontinuation of the 21-h Intravenous N Acetylcysteine Protocol After Acute Acetaminophen Overdose. AB - BACKGROUND: The minimum recommended treatment duration for i.v. N-acetylcysteine (NAC) after an acute, single acetaminophen (APAP) overdose is 21 h. Some have questioned whether shorter courses may be sufficient in carefully selected cases. OBJECTIVE: We sought to describe the incidence of hepatotoxicity in a cohort of acute APAP overdose patients who received <21 h of i.v. NAC for any reason. METHODS: We performed a secondary analysis of a large multicenter retrospective cohort of patients hospitalized for APAP poisoning. We selected patients with a potentially toxic serum APAP concentration measured between 4 and 24 h post ingestion, in whom i.v. NAC was initiated but discontinued before completing the full 21-h course. We further characterized outcomes in these patients as a function of two novel risk-prediction tools, the psi (psi) parameter and APAP * aminotransferase (AT) product. The psi parameter is an estimate of the cellular burden of injury based on the area under the concentration-time curve before treatment, and calculated with respect to the APAP concentration and time to initiation of NAC. RESULTS: Fifty-nine patients met inclusion criteria. Intravenous NAC was initiated a median of 11.3 h post ingestion and administered for a median of 11.0 h. Hepatotoxicity (aspartate aminotransferase [AST] or alanine aminotransferase [ALT] > 1,000 IU/L) occurred in one patient (1.7%; 95% confidence interval 0.04-9.1), and eight additional patients developed hepatic injury (AST or ALT > 100 IU/L). No fatalities occurred. A multiplication product of APAP and AT (APAP * AT) that falls below 10,000 MUmol/L/IU-L, or pretreatment psi < 5 mmol/L-h suggested a low risk of hepatic injury. CONCLUSIONS: In this retrospective analysis of patients treated with < 21 h of i.v. NAC for acute APAP overdose, the incidence of hepatotoxicity and coagulopathy was low, despite delays to NAC treatment. PMID- 26899515 TI - Seizure and Fever. PMID- 26899516 TI - Isolated Intestinal Angioedema in the Emergency Department. AB - BACKGROUND: Angioedema is a condition that can cause cutaneous and mucosal edema of practically any part of the body. Isolated edema of the intestines is a rather rare manifestation, but it can cause important morbidity. Hereditary angioedema as well as certain medications can give rise to intestinal angioedema. We have seen a rise in frequency of intestinal angioedema since the advent of angiotensin converting enzyme inhibitors. Ultrasound of the abdomen is an inexpensive, safe, and easy tool that can help in the differential diagnosis. CASE REPORT: We describe the case of a 25-year-old woman who presented with acute abdominal pain. She was diagnosed with intestinal angioedema due to hereditary angioedema type I. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Misdiagnosis can lead to administering the wrong treatment or even unnecessary surgical interventions. Intestinal angioedema is best treated with purified C1-inhibitor, icatibant, or ecallantide. Fresh frozen plasma is to be avoided because it carries the risk of worsening the symptoms. PMID- 26899517 TI - Acute Cerebellar Ataxia: An Unusual Pediatric Case. AB - BACKGROUND: Acute cerebellar ataxia is a clinical syndrome with sudden onset of uncoordinated gait and normal mental status in young children. Although it has a benign clinical course, it often requires an exhaustive diagnostic work-up in order to rule out potentially life-threatening etiologies that present similarly. The wide differential encompasses causes from infections, brain masses, drugs, toxins, trauma, paraneoplastic syndromes, as well as hereditary or congenital disorders. CASE REPORT: We report on a 4-year-old boy with recent hand-foot-mouth disease who presented with acute cerebellar ataxia. In addition to his marked truncal ataxia and wide-based, staggering gait, he had slowness of speech, which is not commonly reported with this condition in the literature. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physicians have a unique role in being first to evaluate pediatric ataxia and can make a significant impact on identifying potentially fatal mimickers of acute cerebellar ataxia. This article will attempt to outline major diagnostic considerations in order to aid emergency physicians through their clinical approach. PMID- 26899518 TI - Comparison of Unintentional Exposures to Codeine and Hydrocodone Reported to Texas Poison Centers. AB - BACKGROUND: Hydrocodone has recently been reclassified as a Schedule II drug by the United States Drug Enforcement Administration and Food and Drug Administration in order to curtail prescription drug abuse. There is concern that analgesic substitutes, such as codeine, will not be as safe or effective. OBJECTIVE: The purpose of this study is to compare the demographics, adverse events, and medical outcomes of patients who had unintentional hydrocodone or codeine exposures through the use of a state's poison center database. METHODS: The Texas Poison Center Network's database was utilized to find all reported unintentional ingestions or adverse reactions of products containing codeine or hydrocodone. Comparisons were made between the two medications by calculating the rate ratios (RR) and 95% confidence intervals (CI). RESULTS: Children aged 5 years or younger were more exposed to codeine (51.6%). Hydrocodone exposures had more serious outcomes (11% vs. 9%; RR = 0.82; 95% CI 0.73-0.91) and had more nausea (7.1% vs. 2.8%; RR = 0.4; 95% CI 0.32-0.48) and vomiting (6.5% vs. 3.3%; RR = 0.51; 95% CI 0.43-0.62). Hydrocodone had a higher rate of intravenous fluids administration (2.4% vs. 1.7%; RR = 0.71; 95% CI 0.54-0.92) and antiemetics (0.4% vs. 0.1%; RR = 0.23; 95% CI 0.08-0.64). Codeine was more closely associated with dermal reactions and patients were given antihistamines (2.5% vs. 1.3%; RR = 1.88; 95% CI 1.46-2.41) more frequently. Cardiovascular side effects, ataxia, and headache occurred equally between the groups. CONCLUSIONS: Both drugs had a wide array of reported side effects, but the overall incidence of serious outcomes was low. PMID- 26899519 TI - Lemierre Syndrome of the Femoral Vein, Related to Fusobacterium necrophorum Abscess of Vastus Lateralis. AB - BACKGROUND: Lemierre syndrome is an uncommon, potentially lethal disorder combining acute oropharyngeal infection caused by Fusobacterium necrophorum, with jugular vein suppurative thrombosis, complicated by anaerobic sepsis with secondary multiple metastatic abscesses. Optimal treatment outcome with reduced or absence of sequelae can be achieved with early diagnosis. CASE REPORT: We present a clinical case of Fusobacterium necrophorum abscess complicated with femoral vein thrombosis, called atypical localization of Lemierre syndrome. This uncommon disease was diagnosed on the basis of clinical, biological, and imaging tests, with a favorable outcome, after a well-orientated antibiotic and surgical course of therapy. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Since its first description in 1936, Lemierre syndrome has been reported in locations other than its initial oropharyngeal site. Because optimal treatment outcome is dependent on early diagnosis, it is imperative for emergency physicians to be aware of this uncommon disease, because in many instances they are the patient's initial point of contact with medical care. PMID- 26899520 TI - Racial Differences in Pediatric Emergency Department Triage Scores. AB - BACKGROUND: Racial disparities are frequently reported in emergency department (ED) care. OBJECTIVES: To examine racial differences in triage scores of pediatric ED patients. We hypothesized that racial differences existed but could be explained after adjusting for sociodemographic and clinical factors. METHODS: We examined all visits to two urban, pediatric EDs between August 2009 and March 2010. Demographic and clinical data were electronically extracted from the medical record. We used logistic regression to analyze racial differences in triage scores, controlling for possible covariates. RESULTS: There were 54,505 ED visits during the study period, with 7216 (13.2%) resulting in hospital admission. White patients accounted for 36.4% of visits, African Americans 28.5%, Hispanics 18.0%, Asians 4.1%, and American Indians 1.8%. After adjusting for potential confounders, African American (adjusted odds ratio [aOR] 1.89, 95% confidence interval [CI] 1.69-2.12), Hispanic (aOR 1.77, 95% CI 1.55-2.02), and American Indian (aOR 2.57, 95% CI 1.80-3.66) patients received lower-acuity triage scores than Whites. In three out of four subgroup analyses based on presenting complaints (breathing difficulty, abdominal pain, fever), African Americans and Hispanics had higher odds of receiving low-acuity triage scores. No racial differences were detected for patients with presenting complaints of laceration/head injury/arm injury. However, among patients admitted to the hospital, African Americans (aOR 1.47, 95% CI 1.13-1.90) and Hispanics (aOR 1.71, CI 1.22-2.39) received lower-acuity triage scores than Whites. CONCLUSION: After adjusting for available sociodemographic and clinical covariates, African American, Hispanic, and American Indian patients received lower-acuity triage scores than Whites. PMID- 26899521 TI - Appendicitis in the Infant Population: A Case Report and Review of a Four-Month Old With Appendicitis. AB - BACKGROUND: Appendicitis is uncommon in children <6 months old, with few observational studies reporting cases of children younger than 5 years old with the diagnosis. The classic periumbilical pain that migrates to the right lower quadrant, followed by the onset of fever and vomiting, is present in approximately 40% of pediatric patients under 12 years of age with appendicitis. CASE REPORT: A 4-month-old girl presented to the Emergency Department (ED) with acute onset of grunting, pallor, fussiness, emesis, and diarrhea. The patient was initially afebrile, tachycardic, and tachypneic with a soft, nondistended, nontender abdomen and active bowel sounds. The patient became febrile, with a maximum temperature of 39.3 degrees C (102.7 degrees F), and remained tachycardic despite receiving fluids and antipyretics. Laboratory studies were notable for mild dehydration and sterile pyuria. Chest x-ray study was negative for infectious etiologies. Initial abdominal ultrasound found no clear etiology of the patient's symptoms. The patient was admitted to inpatient pediatrics for dehydration, fever, and presumed pyelonephritis. Twenty-four hours later the patient's abdomen became distended and diffusely tender to palpation, with obstipation and increasing episodes of emesis. Abdominal x-ray study demonstrated mild gaseous distension of multiple bowel loops with repeat abdominal ultrasound notable for a focal 8-mm, noncompressible hyperemic structure in the right lower quadrant. The patient was taken to the operating room for a laparoscopic appendectomy. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Appendicitis is a potentially life-threatening condition. In the infant population it frequently presents without the features typically seen in older children. PMID- 26899522 TI - Editorial. PMID- 26899524 TI - A mechanism of Cu work function reduction in CsBr/Cu photocathodes. AB - Thin films of CsBr deposited on Cu(100) have been proposed as next-generation photocathode materials for applications in particle accelerators and free electron lasers. However, the mechanisms underlying an improved photocathode performance as well as their long-term stability remain poorly understood. We present Density Functional Theory (DFT) calculations of the work function reduction following the application of CsBr thin film coatings to Cu photocathodes. The effects of both flat and rough interface and van der Waals forces are examined. Calculations suggest that CsBr films can reduce the Cu(100) work function by about 1.5 eV, which would explain the observed increase in quantum efficiency (QE) of coated vs. uncoated photocathodes. A model explaining the experimentally observed laser activation of photocathodes is provided whereby the photo-induced creation of Br vacancies and Cs-Br di-vacancies and their subsequent diffusion to the Cu/CsBr interface lead to a further increase in QE after a period of laser irradiation. PMID- 26899523 TI - A Clinical Study Evaluating the Effects of Fluvastatin on Serum Osteoprotegerin Levels in Rheumatoid Arthritis Patients. AB - Osteoprotegerin (OPG), a member of the tumor necrosis factor receptor family, has been identified as a critical regulator of bone resorption. Considering the possible role of OPG in rheumatoid arthritis (RA) and in the osteoclastogenesis suppression effects of statins, the present study aims to investigate the effects of fluvastatin on serum levels OPG and disease activity score (DAS) in patients with RA. Forty patients with RA were randomized in a placebo-controlled trial to receive 40 mg fluvastatin or placebo as an adjunct to existing disease-modifying antirheumatic drug (DMARD) therapy (methotrexate, leflunomide, hydroxychloroquine). Patients were followed up over 12 weeks. OPG and disease activity variables were measured at baseline and after 12 weeks of treatment. After 12 weeks, the OPG level was significantly increased in the fluvastatin group compared to the placebo group. DAS-28 was significantly decreased in the fluvastatin group compared to the placebo group. C-reactive protein (CRP), morning stiffness, swollen joint count (SJC), and tender joint count (TJC) were significantly decreased in the fluvastatin group compared to the placebo group; however, erythrocyte sedimentation rate (ESR), modified health assessment questionnaire (MHAQ), and visual analogue screen (VAS) were not changed significantly. In conclusion, fluvastatin administration could increase the OPG levels and improve disease activity variables in patients with RA. Therefore, fluvastatin may serve a potential benefit in the treatment of RA patients. PMID- 26899525 TI - Expression, purification and biochemical characterization of a family 6 carboxylesterase from Methylococcus capsulatus (bath). AB - The genome of Methylococcus capsulatus (bath) encodes a protein R-est6 that is annotated as a lipase family 3 protein. The phylogenetic and the sequence analyses linked this protein to the family 6 carboxylesterase. The gene encoding R-est6 was cloned and overexpressed in Escherichia coli and the recombinant 6x His tagged protein was purified by Ni-NTA affinity chromatography. The buffers used in the purification were modified by adding 1% glycerol instead of the salt to prevent the protein aggregation. Far UV-CD spectrum and gel filtration chromatography of the purified R-est6 confirmed that the protein was well folded like a typical alpha/beta hydrolase and had the quaternary structure of a tetramer, in addition to a compact monomer. The optimum pH was in the range of 7.0-9.0 and the optimum temperature was at 55 degrees C for the hydrolysis of pNP-butyrate. As expected, being a member of the family 6 carboxylesterase, R est6 hydrolyzed triglycerides, pNP esters of the small and the medium fatty acid chain esters and an aryl ester-phenyl acetate. However, R-est6 was also found to hydrolyze the long-chain fatty acid ester which had never been reported for the family 6 carboxylesterase. Additionally, R-est6 was stable and active in the different water-miscible organic solvents. Therefore, the broad substrate range and the structural stability of R-est6 would be advantageous for its application in industrial processes. PMID- 26899526 TI - Differentiating infectious and noninfectious ventilator-associated complications: A new challenge. AB - BACKGROUND: The purpose of this study was to develop an electronic search algorithm which reliably differentiates infectious and noninfectious ventilator associated events (VAEs). This was a retrospective cohort study used to derive a predictive model. It took place at a tertiary care hospital campus. METHODS: Participants included all ventilated patients who met the Centers for Disease Control and Prevention's National Health Safety Network definitions for VAEs between January 1, 2012, and December 31, 2013. There were 164 patients who experienced 185 VAEs in the study period. RESULTS: The most predictive variables were fever 2 days before VAE onset, oxygenation changes, and appearance of respiratory secretions. No other variable, including laboratory tests, radiologic findings, and vital sign values, reached statistical significance. A multivariate regression model was constructed, with 68% sensitivity and 75% specificity (receiver operator characteristic area under the curve [ROC-AUC], 0.83). This was modestly better than the clinical pulmonary infection score (CPIS), which had sensitivity of 50%, specificity of 59%, and ROC-AUC of 0.60. CONCLUSIONS: Although diagnosis of VAEs remains challenging, our data indicate that clinical signs and symptoms of a VAE may be present up to 2 days before they screen positive. Sputum, fever, and oxygenation requirements all were indicative, but aggregate models failed to create a sensitive and specific model for differentiation of VAEs. The existing clinical tool, the CPIS, is also insufficiently sensitive and specific. Further research is needed to create a clinically viable tool for differentiating VAE types at the bedside. PMID- 26899527 TI - Evaluating the impact of an antimicrobial stewardship program on the length of stay of immune-competent adult patients admitted to a hospital ward with a diagnosis of community-acquired pneumonia: A quasi-experimental study. AB - BACKGROUND: The purpose of this study was to demonstrate an antimicrobial stewardship intervention can reduce length of stay for patients admitted to hospital with community-acquired pneumonia (CAP). METHODS: Starting April 1, 2013, consecutive adult patients with CAP admitted to an acute care community hospital in Barrie, Ontario, Canada, were eligible for enrollment until March 31, 2015. The antimicrobial stewardship intervention was a prospective audit and feedback recommendation implemented in a stepped-wedge design across 4 wards. The primary outcome was time to hospital discharge, and secondary outcomes included time to antibiotic discontinuation and a composite outcome of 30-day readmission or all-cause mortality. The intervention effect was estimated by survival (time to discharge and antibiotic discontinuation) and logistic (30-day readmission or all-cause mortality) regression analyses. RESULTS: Complete data were available for 763 patients. The primary outcome was observed in 196 (82%) control patients and 402 (77%) intervention patients. Length of stay was reduced by 11% (95% confidence interval [CI], -9% to 35%). Time to antibiotic discontinuation was shortened by 29% (95% CI, 10%-52%). Odds ratio for 30-day readmission or all cause mortality was 0.79 (95% CI, 0.49-1.29). CONCLUSIONS: A prospective audit and feedback intervention did not significantly reduce length of hospital stay in CAP patients despite reducing overall antibiotic utilization. PMID- 26899528 TI - Disinfection practices in intravenous drug administration. AB - The aim of the study was to determine the effectiveness of a feedback intervention on adherence to disinfection procedures during intravenous medication preparation and administration. We found that full adherence to the protocols significantly improved from 7.3% to 21.5% (P < .001) regarding medication preparation and from 7.9% to 15.5% (P = .012) regarding medication administration. However, disinfection practices still need improvement. PMID- 26899529 TI - Simulation education as a single intervention does not improve hand hygiene practices: A randomized controlled follow-up study. AB - BACKGROUND: To evaluate how critical nurses' knowledge of and adherence to current care hand hygiene (HH) guidelines differ between randomly allocated intervention and control groups before and after simulation education in both a simulation setting and clinical practice during a 2-year follow-up period. It was hypothesized that intervention group knowledge of and adherence to current HH guidelines might increase compared with a control group after simulation education. METHODS: A prospective, parallel, randomized controlled trial with repeated measurements was conducted in a 22-bed adult mixed medical-surgical intensive care unit in Oulu, Finland. Thirty out of 40 initially randomized critical care nurses participated in the baseline measurements; of these, 17 completed all the study procedures. Participants' HH adherence was observed only in high-risk contact situations prior to and postendotracheal suctioning events using a direct, nonparticipatory method of observation. Participants' HH knowledge was evaluated at the end of each observational session. RESULTS: The overall HH adherence increased from a baseline value of 40.8% to 50.8% in the final postintervention measurement at 24 months (P = .002). However, the linear mixed model did not identify any significant group (P = .77) or time-group interactions (P = .17) between the study groups after 2 years of simulation education. In addition, simulation education had no impact on participants' HH knowledge. CONCLUSIONS: After a single simulation education session, critical care nurses' knowledge of and adherence to current HH guidelines remained below targeted behavior rates. PMID- 26899530 TI - Performance characteristics and associated outcomes for an automated surveillance tool for bloodstream infection. AB - BACKGROUND: The objective of this study was to evaluate performance metrics and associated patient outcomes of an automated surveillance system, the blood Nosocomial Infection Marker (NIM). METHODS: We reviewed records of 237 patients with and 36,927 patients without blood NIM using the National Healthcare Safety Network (NHSN) definition for laboratory-confirmed bloodstream infection (BSI) as the gold standard. We matched cases with noncases by propensity score and estimated attributable mortality and cost of NHSN-reportable central line associated bloodstream infections (CLABSIs) and non-NHSN-reportable BSIs. RESULTS: For patients with central lines (CL), the blood NIM had 73.2% positive predictive value (PPV), 99.9% negative predictive value (NPV), 89.2% sensitivity, and 99.7% specificity. For all patients regardless of CL status, the blood NIM had 53.6% PPV, 99.9% NPV, 84.0% sensitivity, and 99.9% specificity. For CLABSI cases compared with noncases, mortality was 17.5% versus 9.4% (P = .098), and median charge was $143,935 (interquartile range [IQR], $89,794-$257,447) versus $115,267 (IQR, $74,937-$173,053) (P < .01). For non-NHSN-reportable BSI cases compared with noncases, mortality was 23.6% versus 6.7% (P < .0001), and median charge was $86,927 (IQR, $54,728-$156,669) versus $62,929 (IQR, $36,743-$115,693) (P < .0001). CONCLUSIONS: The NIM is an effective screening tool for BSI. Both NHSN-reportable and nonreportable BSI cases were associated with increased mortality and cost. PMID- 26899531 TI - The challenge of improving boiling: lessons learned from a randomized controlled trial of water pasteurization and safe storage in Peru. AB - Boiling is the most common method of household water treatment in developing countries; however, it is not always effectively practised. We conducted a randomized controlled trial among 210 households to assess the effectiveness of water pasteurization and safe-storage interventions in reducing Escherichia coli contamination of household drinking water in a water-boiling population in rural Peru. Households were randomized to receive either a safe-storage container or a safe-storage container plus water pasteurization indicator or to a control group. During a 13-week follow-up period, households that received a safe-storage container and water pasteurization indicator did not have a significantly different prevalence of stored drinking-water contamination relative to the control group [prevalence ratio (PR) 1.18, 95% confidence interval (CI) 0.92 1.52]. Similarly, receipt of a safe-storage container alone had no effect on prevalence of contamination (PR 1.02, 95% CI 0.79-1.31). Although use of water pasteurization indicators and locally available storage containers did not increase the safety of household drinking water in this study, future research could illuminate factors that facilitate the effective use of these interventions to improve water quality and reduce the risk of waterborne disease in populations that boil drinking water. PMID- 26899532 TI - Synthesis and carbonic anhydrase I, II, IV and XII inhibitory properties of N protected amino acid - sulfonamide conjugates. AB - N-protected amino acids (Gly, Ala and Phe protected with Boc and Z groups) were reacted with sulfonamide derivatives, leading to the corresponding N-protected amino acid-sulfonamide conjugates. The carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activity of the new compounds was assessed against four human (h) isoforms, hCA I, hCA II, hCA IV and hCA XII. Among them, hCA II, IV and XII are antiglaucoma drug targets, being involved in aqueous humor secretion within the eye. Low nanomolar inhibition was measured against all four isoforms with the 20 reported sulfonamides, but no selective inhibitory profiles, except for some CA XII-selective derivatives, were observed. hCA I, II and XII were generally better inhibited by sulfonamides incorporating longer scaffolds and Gly/Ala, whereas the best hCA IV inhibitors were homosulfanilamide derivatives, incorporating Phe moieties. The amino acid-sulfonamide conjugates show good water solubility and effective hCA II, IV and XII inhibition, and may be considered as interesting candidates for antiglaucoma studies. PMID- 26899535 TI - Gamma knife radiosurgery for pituitary adenomas. AB - Pituitary adenomas are frequently occurring intracranial neoplasms. The aim of the treatment of pituitary adenomas is to normalize hormonal hypersecretion, to preserve the normal pituitary function, to reserve or treat impaired pituitary function and to control tumor growth and its mechanical effects on the surrounding structures. Treatment modalities include surgical, medical and radiation therapy. Radiosurgery is mainly used as a secondary line treatment after surgery for residual or recurrent tumors. The antiproliferative effect is achieved by LKG irradiation in more than 90% of patients. Regarding the functioning pituitary adenomas, the manifestation of the treatment effect is slow and depends mainly on the type of adenoma. Gamma knife irradiation is safe when the maximal doses to pituitary and infundibulum are respected. PMID- 26899536 TI - Solid-phase extraction of explosive nitramines on macroreticular polymers modified by freezing with water or acetone. AB - A novel approach is proposed to modify the porous structure and surface properties of the polymers used in solid-phase extraction. The approach involves soaking in water or acetone, followed by freezing in liquid nitrogen (77.4 K) and was employed for two polymeric materials: Amberlite XAD-7 and Amberlite XAD-16. Variations in the surface properties of the adsorbents were justified by the action of acetone and water as solvents affecting the textural and other characteristic of the materials. The initial and treated adsorbents were used in extraction of explosive nitramines from aqueous samples. The performed modifications of the polymer texture allow us to increase the recovery rate as compared with the initial adsorbents. The results were justified by the swelling of fragments of the polymers and by the additional process of sorption of nitramines. The results indicate that polymeric adsorbents can be easily modified by the soaking/freezing process and the materials can be achieved that prove usefulness for the effective separation of explosive nitramines from aqueous samples. PMID- 26899533 TI - Clinical and biological significance of circulating tumor cells in cancer. AB - During the process of metastasis, which is the leading cause of cancer-related death, cancer cells dissociate from primary tumors, migrate to distal sites, and finally colonize, eventually leading to the formation of metastatic tumors. The migrating tumor cells in circulation, e.g., those found in peripheral blood (PB) or bone marrow (BM), are called circulating tumor cells (CTCs). CTCs in the BM are generally called disseminated tumor cells (DTCs). Many studies have reported the detection and characterization of CTCs to facilitate early diagnosis of relapse or metastasis and improve early detection and appropriate treatment decisions. Initially, epithelial markers, such as EpCAM and cytokeratins (CKs), identified using immunocytochemistry or reverse transcription polymerase chain reaction (RT-PCR) were used to identify CTCs in PB or BM. Recently, however, other markers such as human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), and immuno-checkpoint genes also have been examined to facilitate detection of CTCs with metastatic potential. Moreover, the epithelial-to mesenchymal transition (EMT) and cancer stem cells (CSCs) have also received increasing attention as important CTC markers owing to their roles in the biological progression of metastasis. In addition to these markers, researchers have attempted to develop detection or capture techniques for CTCs. Notably, however, the establishment of metastasis requires cancer-host interactions. Markers from host cells, such as macrophages, mesenchymal stem cells, and bone marrow-derived cells, which constitute the premetastatic niche, may become novel biomarkers for predicting relapse or metastasis or monitoring the effects of treatment. Biological studies of CTCs are still emerging. However, recent technical innovations, such as next-generation sequencing, are being used more commonly and could help to clarify the mechanism of metastasis. Additionally, biological findings are gradually being accumulated, adding to our body of knowledge on CTCs. In this review, we will summarize recent approaches to detect or capture CTCs. Moreover, we will introduce recent studies of the clinical and biological importance of CTCs and host cells. PMID- 26899534 TI - Selective inhibition of tumor cell associated Vacuolar-ATPase 'a2' isoform overcomes cisplatin resistance in ovarian cancer cells. AB - Development of resistance to platinum compounds significantly hinders successful ovarian cancer (OVCA) treatment. In tumor cells, dysregulated pH gradient across cell membranes is a key physiological mechanism of metastasis/chemo-resistance. These pH alterations are mediated by aberrant activation of key multi-subunit proton pumps, Vacuolar-ATPases (V-ATPases). In tumor cells, its 'a2' isoform (V ATPase-V0a2) is a component of functional plasma-membrane complex and promotes tumor invasion through tumor-acidification and immuno-modulation. Its involvement in chemo-resistance has not been studied. Here, we show that V-ATPase-V0a2 is over-expressed in acquired-cisplatin resistant OVCA cells (cis-A2780/cis TOV112D). Of all the 'a' subunit isoforms, V-ATPase-V0a2 exhibited an elevated expression on plasma membrane of cisplatin-resistant cells compared to sensitive counterparts. Immuno-histochemistry revealed V-ATPase-V0a2 expression in both low grade (highly drug-resistant) and high grade (highly recurrent) human OVCA tissues indicating its role in a centralized mechanism of tumor resistance. In cisplatin resistant cells, shRNA mediated inhibition of V-ATPase-V0a2 enhanced sensitivity towards both cisplatin and carboplatin. This improved cytotoxicity was mediated by enhanced cisplatin-DNA-adduct formation and suppressed DNA-repair pathway, leading to enhanced apoptosis. Suppression of V0a2 activity strongly reduced cytosolic pH in resistant tumor cells, which is known to enhance platinum associated DNA-damage. As an indicator of reduced metastasis and chemo resistance, in contrast to plasma membrane localization, a diffused cytoplasmic localization of acidic vacuoles was observed in V0a2-knockdown resistant cells. Interestingly, pre-treatment with monoclonal V0a2-inhibitory antibody enhanced cisplatin cytotoxicity in resistant cells. Taken together, our findings suggest that the isoform specific inhibition of V-ATPase-V0a2 could serve as a therapeutic strategy for chemo-resistant ovarian carcinoma and improve efficacy of platinum drugs. PMID- 26899537 TI - Efficacy of Short-Term Statin Treatment for the Prevention of Contrast-Induced Acute Kidney Injury in Patients Undergoing Coronary Angiography/Percutaneous Coronary Intervention: A Meta-Analysis of 21 Randomized Controlled Trials. AB - BACKGROUND: The results of previous studies have been contradictory in terms of the efficacy of statin treatment in preventing contrast-induced acute kidney injury (CI-AKI) and clinical adverse events (AEs). OBJECTIVE: This meta-analysis was undertaken to assess the role of short-term statin treatment in the prevention of CI-AKI and clinical AEs. METHODS: We searched the Cochrane Library, EMBASE, and PubMed databases for randomized controlled trials (RCTs) with the development of CI-AKI as a primary outcome. Secondary outcomes were the post procedural serum creatinine (SCr) level, estimated glomerular filtration rate (eGFR), and development of AEs. We also performed prespecified subgroup analyses. RESULTS: A total of 21 RCTs involving 7746 patients were included. Short-term statin treatment significantly reduced the risk of CI-AKI [risk ratio (RR) 0.57; 95 % confident interval (CI) 0.47-0.69; p < 0.00001) and was associated with a lower post-procedural SCr level and a higher eGFR. High-dose statins resulted in a lower incidence of CI-AKI than the lower-dose statins. In addition, the benefit was seen across various subgroups for patients at risk of CI-AKI, statin-naive patients, and East Asians, regardless of statin type, definition of CI-AKI, use of N-acetylcysteine (NAC) and hydration, and osmolality of contrast. However, there was no significant difference between the two groups in terms of the incidence of AEs. CONCLUSIONS: The meta-analysis suggests that short-term statin treatment can effectively prevent CI-AKI, and the benefit is also observed in high-risk patients, statin-naive patients, and an East Asian population. However, the effect of simvastatin for the prevention of CI-AKI, of statins for the prevention of AEs, and whether high-dose statins have a better effect than lower dose statins are all still uncertain. PMID- 26899538 TI - Time to Viremia for Patients Taking their First Antiretroviral Regimen and the Subsequent Resistance Profiles. AB - BACKGROUND: The resistance profiles for patients on first-line antiretroviral therapy (ART) regimens after viremia have not been well studied in community clinic settings in the modern treatment era. OBJECTIVE: To determine time to viremia and the ART resistance profiles of viremic patients. METHODS: HIV positive patients aged >=16 years initiating a three-drug regimen were retrospectively identified from 01/01/06 to 12/31/12. The regimens were a backbone of two nucleoside reverse transcriptase inhibitors (NRTIs) and a third agent: a protease inhibitor (PI), non-nucleoside reverse transcriptase inhibitor (NNRTI), or an integrase inhibitor (II). Time to viremia was compared using a proportional hazards model, adjusting for demographic and clinical factors. Resistance profiles were described in those with baseline and follow-up genotypes. RESULTS: For 653 patients, distribution of third-agent use and viremia was: 244 (37%) on PIs with 80 viremia, 364 (56%) on NNRTIs with 84 viremia, and 45 (7%) on II with 11 viremia. Only for NNRTIs, time to viremia was longer than PIs (p = 0.04) for patients with a CD4 count >=200 cells/mm(3). Of the 175 with viremia, 143 (82%) had baseline and 37 (21%) had follow-up genotype. Upon viremia, emerging ART resistance was rare. One new NNRTI (Y181C) mutation was identified and three patients taking PI-based regimens developed NRTI mutations (M184 V, M184I, and T215Y). CONCLUSIONS: Time to viremia for NNRTIs was longer than PIs. With viremia, ART resistance rarely developed without PI or II mutations, but with a few NRTI mutations in those taking PI-based regimens, and NNRTI mutations in those taking NNRTI-based regimens. PMID- 26899540 TI - Clinical Outcomes of Virologically-Suppressed Patients with Pre-existing HIV-1 Drug Resistance Mutations Switching to Rilpivirine/Emtricitabine/Tenofovir Disoproxil Fumarate in the SPIRIT Study. AB - OBJECTIVES: Antiretroviral regimen switching may be considered for HIV-1 infected, virologically-suppressed patients to enable treatment simplification or improve tolerability, but should be guided by knowledge of pre-existing drug resistance. The current study examined the impact of pre-existing drug resistance mutations on virologic outcomes among virologically-suppressed patients switching to Rilpivirine (RPV)/emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF). METHODS: SPIRIT was a phase 3b study evaluating the safety and efficacy of switching to RPV/FTC/TDF in virologically-suppressed HIV-1-infected patients. Pre existing drug resistance at baseline was determined by proviral DNA genotyping for 51 RPV/FTC/TDF-treated patients with known mutations by historical RNA genotype and matched controls and compared with clinical outcome at Week 48. RESULTS: Drug resistance mutations in protease or reverse transcriptase were detected in 62.7% of patients by historical RNA genotype and in 68.6% by proviral DNA genotyping at baseline. Proviral DNA sequencing detected 89% of occurrences of NRTI and NNRTI resistance-associated mutations reported by historical genotype. Mutations potentially affecting RPV activity, including E138A/G/K/Q, Y181C, and H221Y, were detected in isolates from 11 patients by one or both assays. None of the patients with single mutants had virologic failure through Week 48. One patient with pre-existing Y181Y/C and M184I by proviral DNA genotyping experienced virologic failure. Nineteen patients with K103N present by historical genotype were confirmed by proviral DNA sequencing and 18/19 remained virologically-suppressed. DISCUSSION: Virologic success rates were high among virologically-suppressed patients with pre-existing NRTI and NNRTI resistance associated mutations who switched to RPV/FTC/TDF in the SPIRIT study. While plasma RNA genotyping remains preferred, proviral DNA genotyping may provide additional value in virologically-suppressed patients for whom historical resistance data are unavailable. PMID- 26899541 TI - Metabolic effect of pancreatoduodenectomy: Resolution of diabetes mellitus after surgery. AB - BACKGROUND: It is considered natural that glucose tolerance worsens after pancreatectomy. However, diabetes mellitus (DM) resolves after metabolic bypass surgery and anatomic changes after PD resemble those after metabolic surgery. This study assessed the incidence of DM resolution after pancreatectomy and differences in metabolic parameters following pancreatoduodenectomy (PD) and distal pancreatectomy (DP). METHODS: Between 2007 and 2013, 218 consecutive patients with pancreatic diseases underwent PD (n = 112) or DP (n = 106) at Seoul National University Hospital. Factors associated with changes in glucose homeostasis were evaluated by assaying serum glucose concentrations in prospectively collected samples. RESULTS: Of the 218 patients, 88 (40.4%) had preoperative DM, with 27 (30.7%) of the latter showing postoperative resolution of DM, a rate significantly higher in patients who had undergone PD than DP (40.4% vs. 12.9%, p = 0.008). Fasting blood glucose (p = 0.001), PP2 (p < 0.001), and HOMA-IR (p = 0.005) significantly decreased after PD but not after DP. Multivariate analysis revealed that PD was independently associated with DM resolution (odds ratio 7.790, p = 0.003). PD was associated with a significantly higher DM resolution rate than DP among the 37 pancreatic cancer patients with preoperative DM (34.6% vs. 0%, p = 0.036). DM resolution rates were similar in pancreatic cancer and other pancreatic diseases (p = 0.419). CONCLUSION: More than 40% of patients with preoperative DM show resolution after PD. Decreased insulin resistance and suspected enhanced glucose stimulated insulin secretion decreasing PP2 seem to contribute improved glucose homeostasis after PD. BMI was unrelated to DM resolution, indicating that PD-associated physio-anatomical changes may help resolve DM independent of weight. PMID- 26899539 TI - Long-Term Efficacy, Tolerability, and Renal Safety of Atazanavir/Ritonavir-based Antiretroviral Therapy in a Cohort of Treatment-Naive Patients with HIV-1 Infection: the REMAIN Study. AB - BACKGROUND: Boosted protease inhibitors (PIs), including ritonavir-boosted atazanavir (ATV/r), are a recommended option for the initial treatment of HIV-1 infection based upon clinical trial data; however, long-term real-life clinical data are limited. OBJECTIVE: We evaluated the long-term use of ATV/r as a component of antiretroviral combination therapy in the real-life setting in the REMAIN study. METHODS: This was an observational cohort study conducted at sites across Germany, Portugal, and Spain. Retrospective historical and prospective longitudinal follow-up data were extracted every six months from medical records of HIV-infected treatment-naive patients aged >= 18 years initiating a first-line ATV/r-containing regimen. RESULTS: Eligible patients (n = 517) were followed up for a median of 3.4 years. The proportion remaining on ATV/r at 5 years was 51.5% with an estimated Kaplan-Meier median time to treatment discontinuation of 4.9 years. Principal reasons for discontinuation were adverse events (15.9%; 8.9% due to hyperbilirubinemia) and virologic failure (6.8%). The Kaplan-Meier probability of not having virologic failure (HIV-1 RNA < 50 copies/mL) was 0.79 (95% CI: 0.75, 0.83) at five years. No treatment-emergent major PI resistance occurred. ATV/r was generally well tolerated during long-term treatment with no significant changes in estimated glomerular filtration rate over five years. CONCLUSIONS: In a real-life clinical setting over five years, treatment-naive patients with HIV-1 infection initiating an ATV/r-based regimen showed sustained virologic suppression, an overall treatment persistence rate of 51.5%, an absence of treatment-emergent major PI resistance mutations at virologic failure, a long term safety profile consistent with that observed in clinical trials, and no significant decline in renal function. PMID- 26899542 TI - Telomerase activity in pancreatic juice differentiates pancreatic cancer from chronic pancreatitis: A meta-analysis. AB - BACKGROUND/OBJECTIVE: To evaluate the usefulness of genetic markers in pancreatic juice (PJ), and the combination of these markers with telomerase activity in the differential diagnosis of pancreatic ductal adenocarcinoma (PDAC) from chronic pancreatitis. METHODS: We conducted a meta-analysis for the diagnostic utility of the four major altered genes in PDAC (KRAS, CDKN2A/p16, TP53, and SMAD4/DPC4), telomerase activity, and a combination assay using PJ samples. A literature search was conducted in MEDLINE, Cochrane Library, and Web of Science. Data were pooled and presented as diagnostic sensitivity and specificity with 95% confidence intervals (CIs). RESULTS: Thirty-nine studies fulfilled the inclusion criteria. Pooled estimates of KRAS analysis were as follows: sensitivity was 0.67 (95% CI, 0.63-0.71) and specificity, 0.82 (95% CI, 0.79-0.85). For telomerase activity analysis, sensitivity was 0.82 (95% CI, 0.76-0.87) and specificity, 0.96 (95% CI, 0.90-0.99). The other three tumor suppressors demonstrated low sensitivity. The data did not suggest any publication bias. A combined analysis of KRAS and telomerase activity showed a higher diagnostic sensitivity (0.94; 95% CI, 0.83-0.99) than KRAS alone. A combined analysis of telomerase activity and cytology revealed more reliable diagnostic accuracy than telomerase activity alone, with high sensitivity (0.88; 95% CI, 0.74-0.96) and specificity (1.00; 95% CI, 0.91-1.00). CONCLUSIONS: The most reliable marker in PJ samples for diagnosis of PDAC was telomerase activity. Telomerase activity can play a central role in diagnostic analysis using PJ samples, and can increase diagnostic accuracy when combined with KRAS mutations or cytological examination. PMID- 26899543 TI - High flow nasal cannula for respiratory support in preterm infants. AB - BACKGROUND: High flow nasal cannulae (HFNC) are small, thin, tapered binasal tubes that deliver oxygen or blended oxygen/air at gas flows of more than 1 L/min. HFNC are increasingly being used as a form of non-invasive respiratory support for preterm infants. OBJECTIVES: To compare the safety and efficacy of HFNC with other forms of non-invasive respiratory support in preterm infants. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 1), MEDLINE via PubMed (1966 to 1 January 2016), EMBASE (1980 to 1 January 2016), and CINAHL (1982 to 1 January 2016). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: Randomised or quasi-randomised trials comparing HFNC with other non-invasive forms of respiratory support in preterm infants immediately after birth or following extubation. DATA COLLECTION AND ANALYSIS: The authors extracted and analysed data, and calculated risk ratio, risk difference and number needed to treat for an additional beneficial outcome. MAIN RESULTS: We identified 15 studies for inclusion in the review. The studies differed in the interventions compared (nasal continuous positive airway pressure (CPAP), nasal intermittent positive pressure ventilation (NIPPV), non-humidified HFNC, models for delivering HFNC), the gas flows used and the indications for respiratory support (primary support from soon after birth, post-extubation support, weaning from CPAP support). When used as primary respiratory support after birth compared to CPAP (4 studies, 439 infants), there were no differences in the primary outcomes of death (typical risk ratio (RR) 0.36, 95% CI 0.01 to 8.73; 4 studies, 439 infants) or chronic lung disease (CLD) (typical RR 2.07, 95% CI 0.64 to 6.64; 4 studies, 439 infants). HFNC use resulted in longer duration of respiratory support, but there were no differences in other secondary outcomes. One study (75 infants) showed no differences between HFNC and NIPPV as primary support. Following extubation (total 6 studies, 934 infants), there were no differences between HFNC and CPAP in the primary outcomes of death (typical RR 0.77, 95% CI 0.43 to 1.36; 5 studies, 896 infants) or CLD (typical RR 0.96, 95% CI 0.78 to 1.18; 5 studies, 893 infants). There was no difference in the rate of treatment failure (typical RR 1.21, 95% CI 0.95 to 1.55; 5 studies, 786 infants) or reintubation (typical RR 0.91, 95% CI 0.68 to 1.20; 6 studies, 934 infants). Infants randomised to HFNC had reduced nasal trauma (typical RR 0.64, 95% CI 0.51 to 0.79; typical risk difference (RD) -0.14, 95% CI -0.20 to -0.08; 4 studies, 645 infants). There was a small reduction in the rate of pneumothorax (typical RR 0.35, 95% CI 0.11 to 1.06; typical RD -0.02, 95% CI -0.03 to -0.00; 5 studies 896 infants) in infants treated with HFNC. Subgroup analysis found no difference in the rate of the primary outcomes between HFNC and CPAP in preterm infants in different gestational age subgroups, though there were only small numbers of extremely preterm and late preterm infants. One trial (28 infants) found similar rates of reintubation for humidified and non-humidified HFNC, and two other trials (100 infants) found no difference between different models of equipment used to deliver humidified HFNC. For infants weaning from non-invasive respiratory support (CPAP), two studies (149 infants) found that preterm infants randomised to HFNC had a reduced duration of hospitalisation compared with infants who remained on CPAP. AUTHORS' CONCLUSIONS: HFNC has similar rates of efficacy to other forms of non-invasive respiratory support in preterm infants for preventing treatment failure, death and CLD. Most evidence is available for the use of HFNC as post-extubation support. Following extubation, HFNC is associated with less nasal trauma, and may be associated with reduced pneumothorax compared with nasal CPAP. Further adequately powered randomised controlled trials should be undertaken in preterm infants comparing HFNC with other forms of primary non-invasive support after birth and for weaning from non invasive support. Further evidence is also required for evaluating the safety and efficacy of HFNC in extremely preterm and mildly preterm subgroups, and for comparing different HFNC devices. PMID- 26899544 TI - Performance of a specific algorithm to minimize right ventricular pacing: A multicenter study. AB - BACKGROUND: In Boston Scientific dual-chamber devices, the RYTHMIQ algorithm aims to minimize right ventricular pacing. OBJECTIVE: We evaluated the performance of this algorithm determining (1) the appropriateness of the switch from the AAI(R) mode with backup VVI pacing to the DDD(R) mode in case of suspected loss of atrioventricular (AV) conduction and (2) the rate of recorded pacemaker-mediated tachycardia (PMT) when AV hysteresis searches for restored AV conduction. METHODS: In this multicenter study, we included 157 patients with a Boston Scientific dual-chamber device (40 pacemakers and 117 implantable cardioverter defibrillators) without permanent AV conduction disorder and with the RYTHMIQ algorithm activated. We reviewed the last 10 remote monitoring-transmitted RYTHMIQ and PMT episodes. RESULTS: We analyzed 1266 episodes of switch in 142 patients (90%): 207 (16%) were appropriate and corresponded to loss of AV conduction, and 1059 (84%) were inappropriate, of which 701 (66%) were related to compensatory pause (premature atrial contraction, 7%; premature ventricular contraction, 597 (56%); or both, 27 (3%)) or to a premature ventricular contraction falling in the post-atrial pacing ventricular refractory period interval (219, 21%) and 94 (10%) were related to pacemaker dysfunction. One hundred fifty-four PMT episodes were diagnosed in 27 patients (17%). In 85 (69%) of correctly diagnosed episodes, the onset of PMT was directly related to the algorithm-related prolongation of the AV delay, promoting AV dissociation and retrograde conduction. CONCLUSION: This study highlights some of the limitations of the RYTHMIQ algorithm: high rate of inappropriate switch and high rate of induction of PMT. This may have clinical implications in terms of selection of patients and may suggest required changes in the algorithm architecture. PMID- 26899545 TI - PACES/HRS expert consensus statement on the use of catheter ablation in children and patients with congenital heart disease: Developed in partnership with the Pediatric and Congenital Electrophysiology Society (PACES) and the Heart Rhythm Society (HRS). Endorsed by the governing bodies of PACES, HRS, the American Academy of Pediatrics (AAP), the American Heart Association (AHA), and the Association for European Pediatric and Congenital Cardiology (AEPC). PMID- 26899546 TI - Muscle Weakness and Perceived Disability of Upper Limbs in Persons With Late Effects of Polio. AB - BACKGROUND: Muscle weakness in one or both upper limbs is common in persons with previous polio, but there is very limited knowledge how it influences daily life. OBJECTIVE: To assess muscle weakness and self-perceived disability of the upper limbs in persons with late effects of polio and evaluate their association. DESIGN: Cross-sectional study. SETTINGS: University hospital outpatient clinic. PARTICIPANTS: Twenty-eight persons (mean age 67, SD 16 years) with late effects of polio in their upper limbs. MAIN OUTCOME MEASURES: A fixed dynamometer (Biodex System 3 PRO dynamometer (Biodex Medical Systems Inc, Shirley, NY) was used to measure isometric shoulder abduction and elbow flexion, as well as isokinetic concentric elbow flexion and extension. A hand-held dynamometer (Grippit, Hagersten, Sweden) was used to measure isometric grip strength. The Disabilities of Arm, Shoulder and Hand (DASH) questionnaire was used to assess self-perceived disability of the upper limbs. The relationships between the measures were analyzed with the Spearman rank correlation coefficients (rho). RESULTS: The participants were 20%-31% weaker in their more-affected upper limb compared with their less-affected limb. The DASH score was on average 33.5 (SD 18.6), indicating a mild-to-moderate disability of their upper limbs. Changing a lightbulb overhead, carrying a heavy object, and performing recreational activities that required muscle force with the arms were perceived as most difficult. The correlations (rho) between the muscle strength measurements and DASH scores ranged from -0.46 (95% confidence interval [95% CI] -0.10 to -0.71) to -0.61 (95% CI -0.31 to -0.80) for the more affected upper limb, and from -0.54 (95% CI -0.21 to -0.76) to -0.68 (95% CI -0.41 to -0.84) for the less affected upper limb (P < .05-.01). CONCLUSIONS: Persons with previous polio and muscle weakness in their upper limbs perceive difficulties to use their arms in daily life, especially when performing activities above their head and strenuous household or leisure activities. The fair-to-moderate correlations of muscle strength with self-perceived disability imply that the weakness can only partially explain the perceived disabilities of arm, shoulder and hand. Other factors are therefore important to consider in the rehabilitation of persons with late effects of polio and upper limb disability. PMID- 26899547 TI - The Impaired Balance Systems Identified by the BESTest in Older Patients With Knee Osteoarthritis. AB - BACKGROUND: Balance decreases and activities of daily living (ADLs) deteriorate in older people with knee osteoarthritis (KOA); however, little is known about the systems underlying poor balance control and how those impaired systems are related to decreased ADL. OBJECTIVES: To explore which balance systems are particularly impaired and to examine the relationship between physical ADL and balance in older people with KOA. DESIGN: Case-control study. SETTING: Outpatient clinic. PARTICIPANTS: Thirty people with KOA (mean age: 75.4 years) and 30 age matched healthy adults (mean age: 75.4 years). METHODS: The Balance Evaluation Systems Test (BESTest), consisting of 6 sections to evaluate theoretically driven balance control systems, was used for balance assessment. BESTest section scores were compared by use of the Wilcoxon rank-sum test. Pain and physical ADL in the KOA group were evaluated with the Japanese edition of the Western Ontario and McMaster Universities Osteoarthritis Index. Spearman correlation coefficients and partial rank correlation coefficients were used to investigate the relationship between physical ADL and the BESTest scores, pain, radiography findings, and body mass index. MAIN OUTCOME MEASUREMENTS: The BESTest total and section scores. RESULTS: Compared with controls, 5 of 6 BESTest section scores were significantly lower in the KOA group. Physical ADL was significantly correlated with the total BESTest score (r = -0.484, P = .007), pain (r = 0.635, P < .001), Kellgren and Lawrence grade (r = 0.601, P < .001), and body mass index (r = 0.403, P = .027). Partial rank correlation coefficients between physical ADL and the total BESTest score (r = -0.443, P = .021) or section VI-Stability in Gait (r = -0.466, P = .014) were significant after we controlled for other variables. CONCLUSIONS: Most balance systems were impaired in older people with KOA, and this impairment was associated independently with decreased physical ADL. PMID- 26899548 TI - Non-invasive cell type selective in vivo monitoring of insulin resistance dynamics. AB - Insulin resistance contributes to the development of cardio-vascular disease and diabetes. An important but unresolved task is to study the dynamics of insulin resistance in selective cell types of insulin target tissues in vivo. Here we present a novel technique to monitor insulin resistance dynamics non-invasively and longitudinally in vivo in a cell type-specific manner, exemplified by the pancreatic beta-cell situated within the micro-organ the islet of Langerhans. We utilize the anterior chamber of the eye (ACE) as a transplantation site and the cornea as a natural body-window to study the development and reversibility of insulin resistance. Engrafted islets in the ACE that express a FoxO1-GFP-based biosensor in their beta-cells, report on insulin resistance measured by fluorescence microscopy at single-cell resolution in the living mouse. This technique allows monitoring of cell type specific insulin sensitivity/resistance in real-time in the context of whole body insulin resistance during progression and intervention of disease. PMID- 26899549 TI - The usefulness of 'age at first drink' as a concept in alcohol research and prevention. PMID- 26899551 TI - A Ruthenium/Phosphoramidite-Catalyzed Asymmetric Interrupted Metallo-ene Reaction. AB - Allylic chlorides prepared from commercially available trans-1,4-dichloro-2 butene were converted to trans-disubstituted 5- and 6-membered ring systems with perfect diastereoselectivity and high enantioselectivity under chiral ruthenium catalysis. These products contain stereodefined secondary and tertiary alcohols that originate from the trapping of an alkylruthenium intermediate with adventitious water. Key to the success of this transformation was the development of a new BINOL-based phosphoramidite ligand containing bulky substitution at its 3- and 3'-positions. As a demonstration of product utility, diastereoselective Friedel-Crafts reactions were performed on the chiral benzylic alcohols in high yield and stereoselectivity. PMID- 26899550 TI - Ultrasound triggered image-guided drug delivery to inhibit vascular reconstruction via paclitaxel-loaded microbubbles. AB - Paclitaxel (PTX) has been recognized as a promising drug for intervention of vascular reconstructions. However, it is still difficult to achieve local drug delivery in a spatio-temporally controllable manner under real-time image guidance. Here, we introduce an ultrasound (US) triggered image-guided drug delivery approach to inhibit vascular reconstruction via paclitaxel (PTX)-loaded microbubbles (PLM) in a rabbit iliac balloon injury model. PLM was prepared through encapsulating PTX in the shell of lipid microbubbles via film hydration and mechanical vibration technique. Our results showed PLM could effectively deliver PTX when exposed to US irradiation and result in significantly lower viability of vascular smooth muscle cells. Ultrasonographic examinations revealed the US signals from PLM in the iliac artery were greatly increased after intravenous administration of PLM, making it possible to identify the restenosis regions of iliac artery. The in vivo anti-restenosis experiments with PLM and US greatly inhibited neointimal hyperplasia at the injured site, showing an increased lumen area and reduced the ratio of intima area and the media area (I/M ratio). No obvious functional damages to liver and kidney were observed for those animals. Our study provided a promising approach to realize US triggered image guided PTX delivery for therapeutic applications against iliac restenosis. PMID- 26899553 TI - BPTF, a chromatin remodeling-related gene, exhibits frameshift mutations in gastric and colorectal cancers. PMID- 26899552 TI - Recurrent acute thermal lesion induces esophageal hyperproliferative premalignant lesions in mice esophagus. AB - Hot beverage consumption is a risk factor for esophageal squamous cell carcinoma, but the underlying mechanisms are still unknown. We developed an experimental mouse model to understand the mechanism of thermal lesion to esophageal carcinogenesis. Female BALB/c mice were treated by gavage with water at different temperatures three times a week and nitrosamines in the drinking water. Water at 70 degrees C, but not at lower temperatures, initially induced an esophageal necrosis that healed and became resistant to necrosis after further administrations. However, when 70 degrees C water was associated with N nitrosodiethylamine at doses above 1 ppm, there was interference in epithelial regeneration, allowing recurrent thermal injury and inflammation. Recurrent thermal injury resulted in hyper proliferative premalignant lesions being induced earlier (at 4 weeks) and at a higher frequency (4-fold increase at 16 weeks) when compared to mice treated with NDEA only. Ki-67 immunostaining revealed that recurrent thermal injury induced basal cell proliferation resulting in the expansion of epithelial basal cells, confirmed by the increase in cytokeratin 14 positive cells with concomitant reduction of differentiated cytokeratin 5 positive cells. We conclude that recurrent thermal lesion may act as a tumor promoter though a strong proliferation stimulus of esophageal epithelial basal cells. PMID- 26899554 TI - Mean deviation coupling synchronous control for multiple motors via second-order adaptive sliding mode control. AB - A new mean deviation coupling synchronization control strategy is developed for multiple motor control systems, which can guarantee the synchronization performance of multiple motor control systems and reduce complexity of the control structure with the increasing number of motors. The mean deviation coupling synchronization control architecture combining second-order adaptive sliding mode control (SOASMC) approach is proposed, which can improve synchronization control precision of multiple motor control systems and make speed tracking errors, mean speed errors of each motor and speed synchronization errors converge to zero rapidly. The proposed control scheme is robustness to parameter variations and random external disturbances and can alleviate the chattering phenomena. Moreover, an adaptive law is employed to estimate the unknown bound of uncertainty, which is obtained in the sense of Lyapunov stability theorem to minimize the control effort. Performance comparisons with master-slave control, relative coupling control, ring coupling control, conventional PI control and SMC are investigated on a four-motor synchronization control system. Extensive comparative results are given to shown the good performance of the proposed control scheme. PMID- 26899555 TI - Generalized minimum variance control under long-range prediction horizon setups. AB - This paper presents the design and evaluation of a minimal order Generalized Minimum Variance controller with long-range prediction horizon and how it affects the controller and plant output variances. This study investigates how the increased prediction horizon can contribute to mitigate stochastic disturbances and attenuate oscillations. In order to design high order prediction minimum variance filters, a design procedure independent of the Diophantine Equation solution is used. The evaluation is conducted through simulations and practical essays with two different plants: a first order water flow rate problem and a second order under-damped electronic circuit. Both problems are assessed under an incremental control scheme and based on identified stochastic models. Also, two optimal tuning procedures for the algorithm are proposed. PMID- 26899557 TI - Degradation mechanism of a high-performance real micro gas sensor, as determined by spatially resolved XAFS. AB - Of late, battery-driven high-performance gas sensors have gained acceptability in practical usage, whose atomic-scale structure has been revealed by MU fluorescence X-ray absorption fine structure analysis. We studied the chemical distribution of Pd species in the Pd/Al2O3 catalyst overlayer in the real gas sensor at various degrees of deterioration. In a freshly prepared sensor, all Pd species were in the PdO form; in a heavily deteriorated sensor, Pd/Al2O3 in the external region changed to metallic Pd particles, while the PdO structure in the inner region near the heater remained unchanged. The Pd species distribution was in agreement with the simulated thermal distribution. Temperature control was crucial to maintain the high performance of the gas sensor. The improved sensor allows homogeneous heating and has a lifetime of more than 5 years. PMID- 26899556 TI - Discussions about reproductive and sexual health among young adult survivors of cancer. AB - Fertility preservation and sexual health are increasingly important as more young cancer patients survive their disease. Our aims were to describe the frequency with which reproductive and sexual health discussions occur, and to identify clinical factors associated with these discussions. Medical records of patients aged 20-39 diagnosed with solid tumors from 2008-2010 who survived >=2 years were retrospectively reviewed. Multivariate logistic models were used to explore the relationship between clinical factors and occurrence of discussions. We analyzed 427 survivors: median age was 35 years, 29% were men, 88% had baseline [Eastern Cooperative Oncology Group (ECOG)] ECOG 0, and 79% were in a relationship. Only 58% and 7% of patients received discussions about reproductive and sexual health, respectively, at their initial oncology consultation, most of which were led by medical oncologists. There was a significant association between reproductive and sexual health conversations, in that those who engaged in dialog about one topic were more likely to participate in discussions about the other (P = 0.01). Patients with gynecologic malignancies (P < 0.0001) were more inclined to engage in sexual health discussions. Only a minority (19%) of patients took specific action toward fertility preservation, but the receipt of reproductive health discussions was a strong and independent driver for pursuing fertility preservation (P < 0.0001). The impact of cancer and its treatment on fertility and sexual health was inadequately addressed at the time of diagnosis among young cancer survivors. This warrants specific attention since having reproductive health discussions was strongly predictive of patients pursuing fertility preservation strategies. PMID- 26899558 TI - The centriole adjunct of insects: Need to update the definition. AB - The ancestral eukaryotes presumably had an MTOC (microtubule organizing center) which late gave origin to the centriole and the flagellar axoneme. The centrosome of insect early spermatids is in general composed of two components: a single centriole and a cloud of electron-dense pericentriolar material (PCM). During spermiogenesis, the centriole changes its structure and gives rise to a flagellar axoneme, while the proteins of PCM, gamma tubulin in particular, are involved in the production of microtubules for the elongation and shaping of spermatid components. At the end of spermiogenesis, in many insects, additional material is deposited beneath the nucleus to form the centriole adjunct (ca). This material can also extend along the flagellum in two accessory bodies (ab) flanking the axoneme. Among Homoptera Sternorrhyncha, a progressive modification of their sperm flagella until complete disappearance has been verified. In the Archaeococcidae Matsucoccus feytaudi, however, a motile sperm flagellum-like structure is formed by an MTOC activity. This finding gives support to the hypothesis that an evolutionary reversal has occurred in the group and that the cell, when a non-functional centriole is present, activates an ancestral structure, an MTOC, to form a polarized motile bundle of microtubules restoring sperm motility. The presence and extension of the centriole adjunct in the different insect orders is also enlisted. PMID- 26899559 TI - Lake bathymetry and species occurrence predict the distribution of a lacustrine apex predator. AB - This study examined the abiotic and biotic characteristics of ecosystems that allow expression of a life history called ferox trout, the colloquial name given to brown trout Salmo trutta adopting a piscivorous life history strategy, an apex predator in post-glacial lakes in northern Europe. One hundred and ninety-two lakes in Scotland show evidence of currently, or historically, supporting ferox S. trutta; their presence was predicted in logistic models by larger and deeper lakes with a large catchment that also support populations of Arctic charr Salvelinus alpinus. PMID- 26899560 TI - Nitric Oxide is a Central Common Metabolite in Vascular Dysfunction Associated with Diseases of Human Pregnancy. AB - Preeclampsia (PE), gestational diabetes mellitus (GDM), and maternal supraphysiological hypercholesterolaemia (MSPH) are pregnancy-related conditions that cause metabolic disruptions leading to alterations of the mother, fetus and neonate health. These syndromes result in fetoplacental vascular dysfunction, where nitric oxide (NO) plays a crucial role. PE characterizes by abnormal increase in the placental blood pressure and a negative correlation between NO level and fetal weight, suggesting that increased NO level and oxidative stress could be involved. GDM courses with macrosomia along with altered function of the fetal cardiovascular system and fetoplacental vasculature. Even when NO synthesis in the fetoplacental vasculature is increased, NO bioavailability is reduced due to the higher oxidative stress seen in this disease. In MSPH, there is an early development of atherosclerotic lesions in fetal and newborn arteries, altered function of the fetoplacental vasculature, and higher markers of oxidative stress in fetal blood and placenta, thus, vascular alterations related with NO metabolism occur as a consequence of this syndrome. Potential mechanisms of altered NO synthesis and bioavailability result from transcriptional and post translational NO synthases (NOS) modulation, including phosphorylation/dephosphorylation cycles, coupling/uncoupling of NOS, tetrahydrobiopterin bioavailability, calcium/calmodulin-NOS and caveolin-1-NOS interaction. Additionally, oxidative stress also plays a role in the reduced NO bioavailability. This review summarizes the available information regarding lower NO bioavailability in these pregnancy pathologies. A common NO-dependent mechanism in PE, GDM and MSPH contributing to fetoplacental endothelial dysfunction is described. PMID- 26899561 TI - Quantification of Acute Lymphoblastic Leukemia Clonotypes in Leukapheresed Peripheral Blood Progenitor Cells Predicts Relapse Risk after Autologous Hematopoietic Stem Cell Transplantation. AB - Since the incorporation of tyrosine kinase inhibitors into the treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), the notion that all patients with "high-risk" ALL uniformly require allogeneic (allo) hematopoietic cell transplantation (HCT) has received increasing scrutiny. Although multiple studies have shown superiority of alloHCT over autologous (auto) hematopoietic cell transplantation for high-risk patients, these findings may be explained, in part, by contamination of the peripheral blood progenitor cell (PBPC) leukapheresis product by residual leukemic cells in patients undergoing autoHCT. We retrospectively evaluated minimal residual disease (MRD) using next-generation sequencing (NGS) in the PBPC leukapheresis product of 32 ALL patients who underwent autoHCT. Twenty-eight patients (88%) had diagnostic samples with quantifiable immunoreceptor rearrangements to follow for MRD. Twelve (38%) patients had Ph+ B-ALL, 12 (38%) had Philadelphia chromosome-negative (Ph-) B-ALL, and 4 (14%) had T cell ALL. With a median follow-up of 41 months (range, 3 to 217), median relapse-free survival (RFS) and overall survival for the entire cohort were 3.2 and 4.2 years, respectively; at 5 years after transplantation, 42% of patients remain alive and relapse free. Using MRD detection at a threshold of >= 1 * 10(-6), median RFS for patients with detectable MRD was 6.5 months and was not reached for patients without detectable disease (P = .0005). In multivariate analysis, the only factor significantly associated with relapse was the presence of MRD >=1 * 10(-6) (odds ratio, 23.8; confidence interval, 1.8 to 312.9; P = .0158). Our findings suggest that NGS for MRD detection can predict long-term RFS in patients undergoing autoHCT for high-risk ALL. PMID- 26899562 TI - Role of Maintenance Therapy after High-Dose Chemotherapy and Autologous Hematopoietic Cell Transplantation in Aggressive Lymphomas: A Systematic Review. AB - Significant uncertainty exists in regard to the efficacy of maintenance therapy after high-dose chemotherapy (HDC) as well as autologous stem cell transplantation (ASCT) for the treatment of patients with aggressive lymphoma. A systematic review was performed to evaluate the effectiveness of post-ASCT maintenance therapy in patients with relapsed/refractory lymphoma. A comprehensive literature search yielded 4476 studies and a total of 42 studies (11 randomized controlled trials [RCT], 9 retrospective comparative studies, and 22 single-arm studies) were included in the systematic review. There was significant heterogeneity in study design, chemotherapeutic regimens, post-ASCT maintenance strategies, patient enrollment criteria, and study endpoints. Our findings suggest that post-ASCT maintenance immune-targeting strategies, including PD-1/PD-L1 blocking antibodies, rituximab, and brentuximab, may improve progression-free survival but not overall survival. Collectively, the results indicate a need for testing new strategies with well-designed and adequately powered RCTs to better address the role of post-ASCT maintenance in relapsed/refractory lymphomas. PMID- 26899564 TI - The involvement of ankle muscles in maintaining balance in the upright posture is higher in elderly fallers. AB - The purpose of this study was to determine whether the mechanical contribution of ankle muscles in the upright stance differed among young adults (YA) (n=10, age: ~24.3), elderly non-fallers (ENF) (n=12, age: ~77.3) and elderly fallers (EF) (n=20, age: ~80.7). Torque and electromyographic (EMG) activity were recorded on the triceps surae and tibialis anterior during maximum and submaximum contractions in the seated position. EMG activity was also recorded in subjects standing still. Plantar flexor (PF) and dorsal flexor (DF) torques generated in the upright posture were estimated from the torque-EMG relationship obtained during submaximum contractions in the seated position. Center of pressure (CoP) displacement was measured to quantify postural stability. Results showed that, in upright standing, EF generated greater ankle muscle relative torque (i.e. PF+DF torque in the upright stance/PF+DF during maximum isometric torque) than non fallers (i.e. ENF, YA). The greater involvement of ankle muscles in EF was associated with higher CoP displacement. PF+DF torque in the upright stance was no different among the groups, but PF+DF torque during maximum effort was impaired in older groups compared with YA and was lower in EF than ENF. These results suggest that the postural stability impairment observed with aging is highly related to ankle muscle weakness. PMID- 26899563 TI - Overexpression of Suprabasin is Associated with Proliferation and Tumorigenicity of Esophageal Squamous Cell Carcinoma. AB - Suprabasin is a recently identified oncoprotein that is upregulated in multiple cancers. However, the clinical significance and biological role of suprabasin in human esophageal squamous cell carcinoma (ESCC) remains unclear. In the current study, we reported that suprabasin was markedly overexpressed in ESCC cell lines and tissues at both mRNA and protein levels, and this was associated with advanced clinical stage, tumor-nodes-metastasis (TNM) classification, histological differentiation, tumor size and poorer survival. Furthermore, we found that both proliferation and tumorigenicity of ESCC cells were significantly induced by suprabasin overexpression, but inhibited by suprabasin knock-down. Moreover, we demonstrated that upregulation of suprabasin activated the Wnt/beta catenin signaling pathway and led to nuclear localization of beta-catenin and upregulation of Cyclin D1 and c-Myc. Together, our results suggest that suprabasin plays an important oncogenic role in promoting proliferation and tumorigenesis of ESCC. PMID- 26899566 TI - Use of dynamic (18)F-fluorodeoxyglucose positron emission tomography to investigate choroid plexus function in Alzheimer's disease. AB - Choroid plexuses (CPs) are structures involved in CSF production and cerebral regulation and present atypical glucose metabolism. In addition, CPs impairment may be related to Alzheimer disease (AD). In the present study, we present the first results pointing out glucose metabolism in the CP with dynamic fluorodeoxyglucose positron emission tomography (dynamic (18)F-FDG-PET). We studied 47 elderly adults who were classified into three classes: healthy subjects (HS), amnestic mild cognitive impairment (aMCI) and AD. All participants have undergone dynamic (18)F-FDG-PET for 45 min. Acquisitions were divided into 34 frames to extract tissue time-activity curves (TTACs) in various structures including CSF and CPs. Results showed a decreased CPs (18)F-FDG metabolism in AD compared with aMCI and HS. Conversely, dynamic uptake was higher in CSF for AD compared with the other groups. ROC analysis showed that CPs TTACs are a promising tool as it yielded sensitivity of 85.7% and a specificity of 83.3%. Our study showed a disturbance of glucose exchange at the blood-CSF barrier level which is in favour of a key-role of the CPs in AD. PMID- 26899565 TI - Lower gray matter integrity is associated with greater lap time variation in high functioning older adults. AB - BACKGROUND: Lower integrity of cerebral gray matter is associated with higher gait variability. It is not known whether gray matter integrity is associated with higher lap time variation (LTV), a clinically accessible measure of gait variability, high levels of which have been associated with mortality. This study examines the cross-sectional association between gray matter mean diffusivity (MD) and LTV in community-dwelling older adults. METHODS: Study participants consisted of 449 high-functioning adults aged 50 and older (56.8% female) in the Baltimore Longitudinal Study of Aging, free of overt neurological disease. The magnitude of MD in the gray matter, a measure of impaired tissue integrity, was assessed by diffusion tensor imaging in 16 regions of interest (ROIs) involved with executive function, sensorimotor function, and memory. LTV was assessed as variability in lap time based on individual trajectories over ten 40-m laps. Age, sex, height, and weight were covariates. The model additionally adjusted for mean lap time and health conditions that may affect LTV. RESULTS: Higher levels of average MD across 16 ROIs were significantly associated with higher LTV after adjustment for covariates. Specifically, higher MD in the precuneus and the anterior and middle cingulate cortices was strongly associated with higher LTV, as compared to other ROIs. The association persisted after adjustment for mean lap time, hypertension, and diabetes. CONCLUSIONS: Lower gray matter integrity in selected areas may underlie greater LTV in high-functioning community-dwelling older adults. Longitudinal studies are warranted to examine whether changes in gray matter integrity precede more variable gait. PMID- 26899568 TI - The roasting process does not influence the extent of conjugation of coffee chlorogenic and phenolic acids. AB - Understanding the bioavailability and metabolism of coffee compounds will contribute to identify the unknown biological mechanism(s) linked to their beneficial effects. The influence of the roasting process on the metabolism of coffee chlorogenic acids in humans was evaluated. In a randomized, double-blind, crossover study, 12 healthy volunteers consumed four instant coffees namely, high roasted coffee (HRC), low roasted coffee (LRC), unroasted coffee (URC), and in vitro hydrolyzed unroasted coffee (HURC). The sum of areas under the curve (AUC) ranged from 8.65-17.6 to 30.9-126 uM/h (P < 0.05) for HRC, LRC, URC, and HURC, respectively. The AUC of HRC, LRC, and URC was correlated with the initial level of phenolic acids in the coffee drinks. Despite different absorption rates, the extent of conjugation was comparable between HRC, LRC, and URC coffees but different for HURC. The most abundant circulating metabolites during the first 5 H were dihydroferulic acid (DHFA), caffeic acid-3'-O-sulfate (CA3S) and isoferulic-3'-O-glucuronide (iFA3G). DHFA and 5-4-dihydro-m-coumaric acid (mDHCoA) were the main metabolites in the period of 5-24 H. The phenolic compounds after consumption of HURC were most rapidly absorbed (Tmax 1 H) compared with the other coffees (Tmax between 9 and 11 H). Using coffees with different degrees of roasting we highlighted that in spite of different absorption rates the extent of conjugation of phenolic acids was comparable. In addition, by using a hydrolyzed unroasted coffee we demonstrated an increased absorption of phenolic acids in the small intestine. (c) 2016 BioFactors, 42(3):259-267, 2016. PMID- 26899567 TI - Nano-thick calcium oxide armed titanium: boosts bone cells against methicillin resistant Staphylococcus aureus. AB - Since the use of systemic antibiotics for preventing acute biomaterial-associated infections (BAIs) may build up bacterial resistance and result in huge medical costs and unpredictable mortality, new precaution strategies are required. Here, it demonstrated that titanium armed with a nano-thick calcium oxide layer was effective on averting methicillin-resistant Staphylococcus aureus (MRSA) infections in rabbits. The calcium oxide layer was constructed by, firstly, injecting of metallic calcium into titanium via a plasma immersion ion implantation process, and then transforming the outer most surface into oxide by exposing to the atmosphere. Although the calcium oxide armed titanium had a relative low reduction rate (~74%) in growth of MRSA in vitro, it could markedly promote the osteogenic differentiation of bone marrow stem cells (BMSCs), restore local bone integration against the challenge of MRSA, and decrease the incidence of MRSA infection with a rate of 100% (compared to the titanium control). This study demonstrated for the first time that calcium, as one of the major elements in a human body, could be engineered to avert MRSA infections, which is promising as a safe precaution of disinfection for implantable biomedical devices. PMID- 26899570 TI - Testing social-cognitive mediators for objective estimates of physical activity from the Healthy Eating and Active Living for Diabetes in Primary Care Networks (HEALD-PCN) study. AB - OBJECTIVE: More evidence from prospective studies is needed to determine 'if' and 'how' social cognitive constructs mediate behaviour change. In a longitudinal study, we aimed to examine potential social cognitive mediators of objectively measured physical activity (PA) behaviour among people with type 2 diabetes (T2D) who participated in a six-month PA intervention. METHODS: All participants from the proven effective Healthy Eating and Active Living for Diabetes in Primary Care Networks trial were included for this secondary analysis. Change in pedometer-derived daily step counts (baseline to six months) was the outcome of interest. Primary constructs of interest were from Social Cognitive Theory, however constructs from and Theory of Planned Behaviour were also tested in a mediating variable framework using a product-of-coefficients test. RESULTS: The sample (N = 198) had a mean age of 59.5 (SD 8.3) years, haemoglobin A1c 6.8% (SD 1.1), 50% women, BMI 33.6 kg/m(2) (SD 6.5), systolic pressure 125.6 mmHg (SD 16.2) and average daily steps were 5879 (SD 3130). Daily pedometer-determined steps increased for the intervention group compared to usual care control at six months (1481 [SD 2631] vs. 336 [SD 2712]; adjusted p = .002). There was a significant action theory test effect for 'planning' (A = .21, SE = .10, p = .037), and significant conceptual theory test results for 'subjective norms' (B = 657, SE = 312, p = .037) and 'cons' (B = -664, SE = 270, p = .015). None of the constructs satisfied the criteria for mediation. CONCLUSIONS: We were unable to account for the effect of a pedometer-based PA intervention for people with T2D through our examination of mediators. Our findings are inconsistent with some literature concerning PA interventions in diabetes; this may be due to variability in measures used or in study populations. PMID- 26899569 TI - Increased TMEM16A Involved in Alveolar Fluid Clearance After Lipopolysaccharide Stimulation. AB - Transmembrane protein 16A (TMEM16A) regulates a wide variety of cellular activities, including epithelial fluid secretion and maintenance of ion homeostasis. Lipopolysaccharide (LPS), an outer membrane component of Gram negative bacteria, is one of the major causes of acute lung injury (ALI). In this study, we investigated the effects of LPS on the expression of TMEM16A in LA795 cells and mouse lung tissue and the potential mechanism. RESULT: We detected the expression of TMEM16A in LA795 cells and mouse lung tissue by RT-PCR, Western blot, and RNA interference techniques. TMEM16A expression was significantly increased by LPS stimulation in LA795 cells and in mouse lung tissue. Moreover, the LPS-induced TMEM16A expression enhancement in lung tissue was much more prominent in the alveolar epithelial region than in bigger airway epithelial cells. The typical TMEM16A current was recorded, and LPS treatment significantly enhances the current amplitude in LA795 cells. TMEM16A shRNA or TMEM16A inhibitor (T16Ainh-A01) did not affect alveolar fluid clearance (AFC), while co-application of T16Ainh-A01 induced a stronger AFC inhibition than LPS alone. LPS notably and synchronously enhanced Akt phosphorylation (p-Akt) and TMEM16A expression in a time-dependent manner in LA795 cells. Taken together, our results suggest that TMEM16A maybe plays an important role in pathological conditions of LPS-induced ALI as a protective protein. PMID- 26899571 TI - The effect of filled pauses on the processing of the surface form and the establishment of causal connections during the comprehension of spoken expository discourse. AB - The purpose of this study was to examine the effect of filled pauses (uh) on the verification of words and the establishment of causal connections during the comprehension of spoken expository discourse. With this aim, we asked Spanish speaking students to listen to excerpts of interviews with writers, and to perform a word-verification task and a question-answering task on causal connectivity. There were two versions of the excerpts: filled pause present and filled pause absent. Results indicated that filled pauses increased verification times for words that preceded them, but did not make a difference on response times to questions on causal connectivity. The results suggest that, as signals of delay, filled pauses create a break with surface information, but they do not have the same effect on the establishment of meaningful connections. PMID- 26899572 TI - Chronic treatment with epigallocatechin gallate reduces motor hyperactivity and affects in vitro tested intestinal motility of spontaneously hypertensive rats. AB - BACKGROUND: Green tea catechins seem to contribute toward reducing body weight and fat. OBJECTIVE: We aimed to investigate whether chronic administration of (-) epigallocatechin-3-gallate (EGCG), the most abundant catechin of green tea, reduces weight gain in spontaneously hypertensive rats (SHR), an animal model of metabolic syndrome, by increasing motor activity and/or by altering gastrointestinal motility. DESIGN: Nine-week-old SHR were randomly assigned to two groups and treated by gavage for 3 weeks with vehicle dimethyl sulfoxide or EGCG (200 mg/kg/day). Age-matched Wistar-Kyoto (WKY) control rats were treated with vehicle alone. The effect of chronic administration of EGCG was evaluated on open-field motor activity and on ex vivo colonic and duodenal motility. Moreover, in vitro acute effect of 20-min incubation with EGCG (100 uM) or vehicle was evaluated in colonic and duodenal specimens from untreated WKY rats and SHR. RESULTS: Vehicle-treated SHR were normoglycemic and hyperinsulinemic, and showed a reduction of plasma adiponectin when compared to vehicle-treated WKY rats. In addition, consistent with fasting glucose and insulin values, vehicle-treated SHR were more insulin resistant than age-matched vehicle-treated WKY rats. Chronic treatment for 3 weeks with EGCG improved insulin sensitivity, raised plasma adiponectin levels, and reduced food intake and weight gain in SHR. Vehicle treated SHR showed increased open-field motor activity (both crossings and rearings) when tested after each week of treatment. The overall hyperactivity of vehicle-treated SHR was significantly reduced to the levels of vehicle-treated WKY rats after 2 and 3 weeks of EGCG treatment. Colonic and duodenal preparations obtained from SHR chronically treated in vivo with EGCG showed reduced responses to carbachol (0.05-5 uM) and increased inhibitory response to electrical field stimulation (EFS, 1-10 Hz, 13 V, 1 msec, 10-sec train duration), respectively. In vitro acute EGCG incubation (100 uM, 20 min) of colonic and duodenum strips obtained from untreated SHR and WKY rats showed a reduced contractile colonic response to a fixed dose of carbachol (1.5 uM) only in SHR with respect to its own vehicle, whereas the inhibitory duodenal response to a fixed EFS frequency (5 Hz) was significantly reduced in both WKY rats and SHR groups with respect to their own vehicle. CONCLUSIONS: These data suggest that EGCG affects body weight gain in rats and this effect seems to be due to the altered intestinal motility and not to increased motor activity. PMID- 26899573 TI - Inhibitory effects and molecular mechanisms of tetrahydrocurcumin against human breast cancer MCF-7 cells. AB - BACKGROUND: Tetrahydrocurcumin (THC), an active metabolite of curcumin, has been reported to have similar biological effects to curcumin, but the mechanism of the antitumor activity of THC is still unclear. METHODS: The present study was to investigate the antitumor effects and mechanism of THC in human breast cancer MCF 7 cells using the methods of MTT assay, LDH assay, flow cytometry analysis, and western blot assay. RESULTS: THC was found to have markedly cytotoxic effect and antiproliferative activity against MCF-7 cells in a dose-dependent manner with the IC50 for 24 h of 107.8 MUM. Flow cytometry analysis revealed that THC mediated the cell-cycle arrest at G0/G1 phase, and 32.8% of MCF-7 cells entered the early phase of apoptosis at 100 MUM for 24 h. THC also dose-dependently led to apoptosis in MCF-7 cells via the mitochondrial pathway, as evidenced by the activation of caspase-3 and caspase-9, the elevation of intracellular ROS, a decrease in Bcl-2 and PARP expression, and an increase in Bax expression. Meanwhile, cytochrome C was released to cytosol and the loss of mitochondria membrane potential (Deltapsim) was observed after THC treatment. CONCLUSION: THC is an excellent source of chemopreventive agents in the treatment of breast cancer and has excellent potential to be explored as antitumor precursor compound. PMID- 26899574 TI - Serum Resistin Levels May Contribute to an Increased Risk of Acute Cerebral Infarction. AB - The objective of this study was to investigate the association between serum resistin levels and acute cerebral infarction (ACI). PubMed, SpringerLink, Wiley, EBSCO, Ovid, Web of Science, Wanfang, China National Knowledge Infrastructure, and VIP databases (last updated search in October 2014) were exhaustively searched, and data from the eligible studies were extracted and analyzed to assess the association between serum resistin levels and ACI. STATA software (version 12.0, Stata Corporation, College Station, TX, USA) was utilized for data analysis. Ten studies including 1829 ACI patients and 1557 healthy controls were eligible for inclusion in the meta-analysis. Our major result revealed that ACI patients exhibited higher serum resistin levels compared with healthy controls. Asubgroup analysis based on ethnicity showed a significant association between serum resistin levels and ACI in Asians, but surprisingly not in Caucasians. The results of our meta-analysis suggest that serum resistin levels are associated with an increased risk of ACI. PMID- 26899577 TI - Common Limb Length Does Not Influence Weight Loss After Standard Laparoscopic Roux-En-Y Gastric Bypass. PMID- 26899578 TI - In vitro effect of octenidine dihydrochloride against Trichomonas vaginalis. AB - Trichomoniasis is the most common non-viral sexually transmitted disease. It is associated with a wide spectrum of complications, including infertility and increased susceptibility to human immunodeficiency virus (HIV). A rising number of reports of Trichomonas vaginalis strains resistant to metronidazole has driven the search for new compounds. In the present study, the in vitro effects of the common antiseptic octenidine dihydrochloride against T. vaginalis were tested on metronidazole-resistant and -susceptible strains. Assays were performed under microaerophilic conditions in three different media containing varying concentrations of protein. It was shown that octenidine dihydrochloride is highly effective against T. vaginalis, with no difference between metronidazole resistant and -susceptible strains. The 50% effective concentration (EC50) values ranged from 5.7 to 21.37MUg/mL after 5min, from 6.48 to 10.82MUg/mL after 15min and from 0.68 to 2.11MUg/mL after 30min of treatment depending on the protein concentration of the test medium. Octenidine dihydrochloride, already approved in some countries for the treatment of bacterial and fungal vaginal infections, appears to be a promising alternative treatment for trichomoniasis, particularly in mixed vaginal infections or in cases caused by metronidazole-resistant strains. PMID- 26899579 TI - Could Better Phenotyping Small Vessel Disease Provide New Insights into Alzheimer Disease and Improve Clinical Trial Outcomes? AB - Alzheimer Disease (AD) is the most common primary cause of dementia with a burgeoning epidemic as life expectancy and general medical care improve worldwide. Recent data from pathologic studies has shown that the cooccurrence of other neurodegenerative and vascular pathologies is in fact the rule rather than the exception. In late onset AD, cerebral small vessel disease (SVD) is almost invariably co-existent to a greater or lesser extent and is known to promote cognitive deterioration. Previous observational studies and clinical trials have largely sought to divide dementia based on predominant neurodegenerative or vascular mechanisms. Given the high degree of overlap, findings from such studies may be difficult to interpret and apply to population cohorts. Additionally opportunities may be lost for uncovering novel interventions that target interactions between co-existent vascular and neurodegenerative pathologies. In the current review, we consider potential pathophysiologic mechanisms through which SVD may be associated with and promote AD pathology. In particular we explore shared environmental and genetic associations and how these may converge via neuroinflammatory pathways potentially providing novel therapeutic targets. SVD has heterogenous manifestations on cerebral imaging and at pathology. We discuss how studying SVD topography may enable us to better identify those at risk for more rapid cognitive decline and improve future clinical trial design. PMID- 26899580 TI - Peripheral Immune Signatures in Alzheimer Disease. AB - According to the current paradigm, the main cause of AD is the accumulation of neurotoxic amyloid beta (Abeta) peptide aggregates resulting from the cleavage of the amyloid precursor protein into peptides of different length, with the 42 amino acid long Abeta42 being the most toxic form. Abeta can aggregate and form plaques in the brain. It further promotes the hyperphosphorylation of the tau protein which forms characteristic neurofibrillary tangles and thereby loses its important role in axonal transport and contributes to neurodegeneration. Therefore, treatments have targeted Abeta, but clinical trials of immunotherapies caused severe side effects and showed that Abeta clearance alone did not result in any cognitive improvement. This leads to the question: what else promotes AD pathology? Here, we review data on systemic inflammation and the possible roles that the immune system might play in AD. Microglia and astrocytes are activated and secrete inflammatory cytokines and chemokines. Via a disturbed blood-brain barrier, peripheral immune cells are activated and recruited towards inflamed brain lesions and amyloid plaques, but due to the chronic nature of the amyloid burden and their reduced function, these cells are not able to control inflammation and the associated detrimental immune responses. In addition, age related inflammation and chronic infection with herpes viruses might contribute to the systemic inflammation and exacerbate attempts to restore the balance of inflammation. PMID- 26899576 TI - A Novel, Multi-Target Natural Drug Candidate, Matrine, Improves Cognitive Deficits in Alzheimer's Disease Transgenic Mice by Inhibiting Abeta Aggregation and Blocking the RAGE/Abeta Axis. AB - The treatment of AD is a topic that has puzzled researchers for many years. Current mainstream theories still consider Abeta to be the most important target for the cure of AD. In this study, we attempted to explore multiple targets for AD treatments with the aim of identifying a qualified compound that could both inhibit the aggregation of Abeta and block the RAGE/Abeta axis. We believed that a compound that targets both Abeta and RAGE may be a feasible strategy for AD treatment. A novel and small natural compound, Matrine (Mat), was identified by high-throughput screening of the main components of traditional Chinese herbs used to treat dementia. Various experimental techniques were used to evaluate the effect of Mat on these two targets both in vitro and in AD mouse model. Mat could inhibit Abeta42-induced cytotoxicity and suppress the Abeta/RAGE signaling pathway in vitro. Additionally, the results of in vivo evaluations of the effects of Mat on the two targets were consistent with the results of our in vitro studies. Furthermore, Mat reduced proinflammatory cytokines and Abeta deposition and attenuated the memory deficits of AD transgenic mice. We believe that this novel, multi-target strategy to inhibit both Abeta and RAGE, is worthy of further exploration. Therefore, our future studies will focus on identifying even more effective multi-target compounds for the treatment of AD based on the molecular structure of Mat. PMID- 26899575 TI - Citalopram Ameliorates Synaptic Plasticity Deficits in Different Cognition Associated Brain Regions Induced by Social Isolation in Middle-Aged Rats. AB - Our previous experiments demonstrated that social isolation (SI) caused AD-like tau hyperphosphorylation and spatial memory deficits in middle-aged rats. However, the underlying mechanisms of SI-induced spatial memory deficits remain elusive. Middle-aged rats (10 months) were group or isolation reared for 8 weeks. Following the initial 4-week period of rearing, citalopram (10 mg/kg i.p.) was administered for 28 days. Then, pathophysiological changes were assessed by performing behavioral, biochemical, and pathological analyses. We found that SI could cause cognitive dysfunction and decrease synaptic protein (synaptophysin or PSD93) expression in different brain regions associated with cognition, such as the prefrontal cortex, dorsal hippocampus, ventral hippocampus, amygdala, and caudal putamen, but not in the entorhinal cortex or posterior cingulate. Citalopram could significantly improve learning and memory and partially restore synaptophysin or PSD93 expression in the prefrontal cortex, hippocampus, and amygdala in SI rats. Moreover, SI decreased the number of dendritic spines in the prefrontal cortex, dorsal hippocampus, and ventral hippocampus, which could be reversed by citalopram. Furthermore, SI reduced the levels of BDNF, serine-473 phosphorylated Akt (active form), and serine-9-phosphorylated GSK-3beta (inactive form) with no significant changes in the levels of total GSK-3beta and Akt in the dorsal hippocampus, but not in the posterior cingulate. Our results suggest that decreased synaptic plasticity in cognition-associated regions might contribute to SI-induced cognitive deficits, and citalopram could ameliorate these deficits by promoting synaptic plasticity mainly in the prefrontal cortex, dorsal hippocampus, and ventral hippocampus. The BDNF/Akt/GSK-3beta pathway plays an important role in regulating synaptic plasticity in SI rats. PMID- 26899581 TI - Traumatic Brain Injury as a Risk Factor for Alzheimer's Disease: Is Inflammatory Signaling a Key Player? AB - Traumatic brain injury (TBI) has become a significant medical and social concern within the last 30 years. TBI has acute devastating effects, and in many cases, seems to initiate long-term neurodegeneration. With advances in medical technology, many people are now surviving severe brain injuries and their long term consequences. Post trauma effects include communication problems, sensory deficits, emotional and behavioral problems, physical complications and pain, increased suicide risk, dementia, and an increased risk for chronic CNS diseases, such as Alzheimer's disease (AD). In this review, we provide an introduction to TBI and hypothesize how it may lead to neurodegenerative disease in general and AD in particular. In addition, we discuss the evidence that supports the hypothesis that TBI may lead to AD. In particular, we focus on inflammatory responses as key processes in TBI-induced secondary injury, with emphasis on nuclear factor kappa B (NF-kappaB) signaling. PMID- 26899582 TI - Direct single-shot phase retrieval from the diffraction pattern of separated objects. AB - The non-crystallographic phase problem arises in numerous scientific and technological fields. An important application is coherent diffractive imaging. Recent advances in X-ray free-electron lasers allow capturing of the diffraction pattern from a single nanoparticle before it disintegrates, in so-called 'diffraction before destruction' experiments. Presently, the phase is reconstructed by iterative algorithms, imposing a non-convex computational challenge, or by Fourier holography, requiring a well-characterized reference field. Here we present a convex scheme for single-shot phase retrieval for two (or more) sufficiently separated objects, demonstrated in two dimensions. In our approach, the objects serve as unknown references to one another, reducing the phase problem to a solvable set of linear equations. We establish our method numerically and experimentally in the optical domain and demonstrate a proof-of principle single-shot coherent diffractive imaging using X-ray free-electron lasers pulses. Our scheme alleviates several limitations of current methods, offering a new pathway towards direct reconstruction of complex objects. PMID- 26899585 TI - Evaluation of functional methods for human movement modelling. AB - PURPOSE: accurate assessment of human joint parameters is a critical issue for the quantitative movement analysis, due to a direct influence on motion patterns. In this study three different known functional methods are experimentally compared to identify knee joint kinematics for further gait and motion analysis purposes. METHODS: taking into account the human knee physiology complexity, within its roto-translation, the study is conducted on a lower limb mechanical analogue with a polycentric hinge-based kinematic model. The device mimics a joint with a mobile axis of rotation whose position is definable. Sets of reflective markers are placed on the dummy and flexion-extension movements are imposed to the shank segment. Marker positions are acquired using an optoelectronic motion capture system (Vicon 512). RESULTS: acquired markers' positions are used as input data to the three functional methods considered. These ones approximate the polycentric knee joint with a fixed single axis model. Different ranges of motion and number of markers are considered for each functional method. Results are presented through the evaluation of accuracy and precision concerning both misalignment and distance errors between the estimated axis of rotation and the instantaneous polycentric one, used as reference. CONCLUSION: the study shows the feasibility of the identification of joint parameters with functional approaches applied on a polycentric mechanism, differently from those usually conceived by the reviewed algorithms. Moreover, it quantifies and compares the approximation errors using different algorithms, by varying number and position of markers, as well ranges of motion. PMID- 26899583 TI - Gender, Position of Authority, and the Risk of Depression and Posttraumatic Stress Disorder among a National Sample of U.S. Reserve Component Personnel. AB - BACKGROUND: Recent U.S. military operations in Iraq and Afghanistan have seen dramatic increases in the proportion of women serving and the breadth of their occupational roles. General population studies suggest that women, compared with men, and persons with lower, as compared with higher, social position may be at greater risk of posttraumatic stress disorder (PTSD) and depression. However, these relations remain unclear in military populations. Accordingly, we aimed to estimate the effects of 1) gender, 2) military authority (i.e., rank), and 3) the interaction of gender and military authority on a) risk of most recent deployment related PTSD and b) risk of depression since most recent deployment. METHODS: Using a nationally representative sample of 1,024 previously deployed Reserve Component personnel surveyed in 2010, we constructed multivariable logistic regression models to estimate effects of interest. RESULTS: Weighted multivariable logistic regression models demonstrated no statistically significant associations between gender or authority, and either PTSD or depression. Interaction models demonstrated multiplicative statistical interaction between gender and authority for PTSD (beta = -2.37; p = .01), and depression (beta = -1.21; p = .057). Predicted probabilities of PTSD and depression, respectively, were lowest in male officers (0.06, 0.09), followed by male enlisted (0.07, 0.14), female enlisted (0.07, 0.15), and female officers (0.30, 0.25). CONCLUSIONS: Female officers in the Reserve Component may be at greatest risk for PTSD and depression after deployment, relative to their male and enlisted counterparts, and this relation is not explained by deployment trauma exposure. Future studies may fruitfully examine whether social support, family responsibilities peri-deployment, or contradictory class status may explain these findings. PMID- 26899584 TI - Rapid response team and hospital mortality in hospitalized patients. AB - PURPOSE: Although rapid response systems are known to reduce in-hospital cardiac arrest rate, their effect on mortality remains debated. The present study aimed to evaluate the effect of implementing an intensivist-led rapid response team (RRT) on mortality in hospitalized patients. METHODS: An implementation of an intervention and a comparison with retrospective data analysis were performed in the four hospitals of Montpellier regional healthcare centre, in France. An intensivist-led RRT was implemented on a 24/7 basis along with educational modules, publicity and bedside simulation-based training in only one of the four hospitals from January 2012 to June 2012. A single activation criterion (heart rate below 40/min or above 140/min, systolic blood pressure below 80 mmHg, cardiac arrest, respiratory rate below 8/min or above 30/min, pulse oximetry below 90% with O2 above 6 l/min, respiratory distress in a tracheotomised patient, respiratory arrest, coma or sudden change in level of consciousness, seizure) allowed any caregiver to directly contact the RRT using a dedicated cell phone number. Patients over 18 years admitted for more than 24 h in the medical surgical wards from July 2010 to December 2011 (pre-RRT period) and from July 2012 to December 2013 (RRT period) were included. The main outcome was unexpected mortality. Analyses of data from one RRT hospital and three control hospitals (no RRT hospital) were performed. RESULTS: RRT implementation was associated with a decrease in unexpected mortality rate in the hospital that implemented RRT (from 21.9 to 17.4 per 1000 discharges; p = 0.002). Reduction in unexpected mortality associated with RRT implementation could be estimated at 1.5 lives saved per week in the RRT hospital. In the three other hospitals, mortality rate was not significantly modified (from 19.5 to 19.9 per 1000 discharges; p = 0.69). Overall mortality decreased from 39.6 to 34.6 per 1000 discharges between the pre-RRT and RRT period in the RRT hospital (p = 0.012), but did not significantly change in the other hospitals. Patients in the RRT hospital were more frequently admitted to the intensive care unit (ICU) during the RRT period (45.8 vs 52.9 per 1000; p = 0.002), and their sequential organ failure assessment (SOFA) score upon ICU admission significantly decreased from 7 (4-10) to 5 (2-9); p < 0.001. CONCLUSIONS: In the present retrospective study, implementation of an intensivist led RRT along with educational modules, publicity and bedside simulation-based training was associated with a significant decrease in unexpected and overall mortality of inpatients. PMID- 26899586 TI - Differential response properties of peripherally and cortically evoked swallows by electrical stimulation in anesthetized rats. AB - We compared onset latency, motor-response patterns, and the effect of electrical stimulation of the cortical masticatory area between peripherally and cortically evoked swallows by electrical stimulation in anesthetized rats. The number of swallows and the motor patterns were determined using electromyographic recordings from the thyrohyoid, digastric, and masseter muscles. The onset latency of the first swallow evoked by electrical stimulation of the cortical swallowing area (Cx) was significantly longer than that evoked by stimulation of the superior laryngeal nerve (SLN). The duration of thyrohyoid burst activity associated with SLN-evoked swallows was significantly longer than that associated with either Cx-evoked or spontaneous swallows. Combining Cx with SLN stimulation increased the number of swallows at low levels of SLN stimulation. Finally, A area (the orofacial motor cortex) stimulation inhibited Cx-evoked swallows significantly more than it inhibited SLN-evoked swallows. These findings suggest that peripherally and cortically evoked swallows have different response properties and are affected differently by the mastication network. PMID- 26899587 TI - Stimulant treatment history predicts frontal-striatal structural connectivity in adolescents with attention-deficit/hyperactivity disorder. AB - Diffusion tensor imaging (DTI) has revealed white matter abnormalities in individuals with attention-deficit/hyperactivity disorder (ADHD). Stimulant treatment may affect such abnormalities. The current study investigated associations between long-term stimulant treatment and white matter integrity within the frontal-striatal and mesolimbic pathways, in a large sample of children, adolescents and young adults with ADHD. Participants with ADHD (N=172; mean age 17, range 9-26) underwent diffusion-weighted MRI scanning, along with an age- and gendermatched group of 96 control participants. Five study-specific white matter tract masks (orbitofrontal-striatal, orbitofrontal-amygdalar, amygdalar-striatal, dorsolateral-prefrontal-striatal and medialprefrontal striatal) were created. First we analyzed case-control differences in fractional anisotropy (FA) and mean diffusivity (MD) within each tract. Second, FA and MD in each tract was predicted from cumulative stimulant intake within the ADHD group. After correction for multiple testing, participants with ADHD showed reduced FA in the orbitofrontal-striatal pathway (p=0.010, effect size=0.269). Within the ADHD group, higher cumulative stimulant intake was associated with lower MD in the same pathway (p=0.011, effect size=-0.164), but not with FA. The association between stimulant treatment and orbitofrontal-striatal MD was of modest effect size. It fell short of significance after adding ADHD severity or ADHD type to the model (p=0.036 and p=0.094, respectively), while the effect size changed little. Our findings are compatible with stimulant treatment enhancing orbitofrontal-striatal white matter connectivity, and emphasize the importance of the orbitofrontal cortex and its connections in ADHD. Longitudinal studies including a drug-naive baseline assessment are needed to distinguish between subject variability in ADHD severity from treatment effects. PMID- 26899589 TI - Maternity staff perspectives regarding resource demands of breastfeeding supportive practices in accordance with the Baby-Friendly Hospital Initiative accreditation: a Q methodology approach. AB - AIM: To explore the resource demands of implementing the Baby-Friendly Hospital Initiative among maternity staff. BACKGROUND: Implementing the Baby-Friendly Hospital Initiative is the most recognized global strategy for ensuring that hospital routines support breastfeeding. The maternity services of Baby-Friendly Hospital Initiative accredited hospitals are evaluated according to the Ten Steps to Successful Breastfeeding. DESIGN: Q methodology was applied to investigate the perspectives of 60 maternity staff in Northern Taiwan. METHODS: Data were collected from May - December 2014. An online Q-sort platform was designed for the participants to perform sorting. The Q-sorts were subjected to factor analysis by using PQ Method software. Factors were extracted using principal component analysis with a varimax rotation. A combination of eigenvalues and a scree plot were employed to determine the number of retained factors. RESULTS: Four factors retained in the final model accounted for 56% of the total variance: (1) emphasis on implementing an institutional policy; (2) emphasis on providing supportive practices for breastfeeding mothers; (3) emphasis on establishing continual breastfeeding support; and (4) emphasis on managing breastfeeding supportive practices concerning a designated time period. The participants that were associated with Factors 1 and 3 emphasized the necessity of allocating resources to Steps 1, 2 and 10 of the Ten Steps. The participants associated with Factors 2 and 4 emphasized allocating resources to Steps 2-5 and 7. CONCLUSIONS: This study revealed the various perspectives of maternity staff regarding the resource demands of implementing the Baby-Friendly Hospital Initiative. These perspectives may serve as a reference for decision-makers in prioritizing resource allocation. PMID- 26899588 TI - Randomized controlled study of early medication change for non-improvers to antidepressant therapy in major depression--The EMC trial. AB - Patients with Major Depressive Disorder (MDD) and no improvement after two weeks of antidepressant pharmacotherapy have a high risk of treatment failure. The aim of the study was to determine whether an early medication change (EMC) strategy is superior to a guideline-based treatment in MDD patients without improvement after two weeks of antidepressant pharmacotherapy. Eight-hundred-and-eighty-nine patients with MDD were enrolled, 879 patients received the SSRI escitalopram. Of those, 192 patients had no improvement, defined as a reduction of < 20% on the Hamilton Depression Rating Scale (HAMD-17) after 14 days of treatment, and were randomly assigned to open treatment with the EMC strategy (n = 97; venlafaxine XR for study days 15-56; in case of sustained non-improvement on day 28, lithium augmentation for days 29-56) or TAU (n = 95; escitalopram continuation; non responders on day 28 were switched to venlafaxine XR for four weeks, i.e. days 29 56). The primary outcome was remission (HAMD-17 <= 7) after 8 weeks of treatment as assessed by blinded raters. Remission rates were 24% for EMC and 16% for TAU, which was not significantly different (p = 0.2056). Sensitivity analyses for the primary and secondary effectiveness endpoints consistently showed favorable results for patients randomized to EMC. The results confirm data from post-hoc analyses of clinical trials showing that early non-improvement identifies patients who likely need alternate interventions. However, the herein used two step switch/augmentation strategy for this risk group was not more effective than the control intervention. Alternate strategies and other design aspects are discussed in order to support researchers addressing the same research question. PMID- 26899590 TI - Intra-arterial nitroglycerin for intra-operative arterial vasospasm during pediatric renal transplantation. AB - Intra-operative arterial vasospasm during pediatric renal transplantation is an urgent clinical situation resulting in end-organ ischemia, associated changes in parenchymal turgor and color, diminished flow on ultrasound, and if left untreated, allograft loss. We hypothesized that intra-operative intra-arterial injection of nitroglycerin would reverse vasospasm and improve renal perfusion. A three-yr-old girl with end-stage renal disease due to autosomal recessive polycystic kidney disease on peritoneal dialysis underwent deceased donor renal transplantation. After optimal immediate reperfusion and hemodynamic parameters, the kidney lost turgor and became mottled in appearance despite adequate hilar arterial and venous Doppler waveforms. Two aliquots of 40 MUg (0.4 mL of a 100 MUg/mL) nitroglycerin solution were injected directly into the renal artery 10 min apart. Nitroglycerin resulted in dramatic change in the consistency and appearance of the allograft. An improvement in renal blood flow was demonstrated by ultrasound after the second intra-arterial nitroglycerin injection with only a transient decrease in systemic arterial blood pressure. The child experienced normal allograft perfusion on serial postoperative ultrasounds, with a prompt decrease in serum creatinine and excellent diuresis. Intra-arterial nitroglycerin is a promising option for intra-operative arterial vasospasm during pediatric renal transplantation with objective improvement in blood flow and perfusion. PMID- 26899591 TI - Growth and Deposition of Au Nanoclusters on Polymer-wrapped Graphene and Their Oxygen Reduction Activity. AB - The development of a non-Pt electrocatalyst with a high performance for the oxygen reduction reaction (ORR) is one of the central issues in polymer electrolyte fuel cells science. Au-nanoparticles (Au-NPs) with a diameter of <2 nm are one of the promising substitutes of Pt-NPs; however, it is still a challenge to synthesize such a small-sized Au-NPs with a narrow diameter distribution on a carbon support without using capping agents. We here describe a facile method to deposit uniform Au-NPs (diameter = 1.6 nm and 3.3 nm) on the stacked-graphene (<10 layers) coated with poly[2,2'-(2,6-pyridine)-5,5' bibenzimidazole] without using any capping agents. The obtained Au-NPs exhibit an excellent ORR activity with the onset potential at -0.11 V and -0.09 V (vs. Ag/AgCl) for 1.6 nm and 3.3 nm, respectively. On the other hand, inhomogeneous Au NPs with 4.6 nm in average diameter shows the onset potential at -0.15 V (vs. Ag/AgCl). PMID- 26899592 TI - Effects of Oriental Medicine Kyung-Ok-Ko on Uterine Abnormality in Hyperandrogenized Rats. AB - A traditional herbal prescription Kyung-Ok-Ko (KOK), composed of Rehmannia glutinosa Liboschitz var. purpurae, Lycium chinense, Aquilaria agallocha, Poria cocos, Panax ginseng, and honey, has been widely used in Oriental medicine as an invigorant for age-related diseases, such as amnesia and stroke. However, the beneficial value of KOK on uterine dysfunction related to hyperandrogenism is largely unknown. We investigated the effect of KOK (2.0 g/kg/day, per os) on endometrial abnormalities in a dehydroepiandrosterone (DHEA, subcutaneous) induced polycystic ovary syndrome (PCOS) rat model. Preadministration of KOK significantly (p<0.05) decreased the elevated body weight, uterus weight, and endometrial thickness by PCOS induction, corresponding to reduced apoptosis and the infiltration of immune cells (CD4+ T cells, CD8+ T cells, and macrophages) in the endometrium. These results were associated with reduced mRNA expression of interleukin (IL)-1beta, IL-6, IL-8, and matrix metalloproteinase-3 and increased mRNA expression of IGF-beta1, transforming growth factor (TGF)-beta, TGF-beta1, and vascular endothelial growth factor in the uterus after DHEA injection. These multiple effects of KOK may synergistically prevent the development of endometrial abnormalities in DHEA-induced hyperandrogenism via anti-inflammatory action, indicating that KOK has preventive and therapeutic potential for suppressing PCOS. PMID- 26899594 TI - Design, RNA cleavage and antiviral activity of new artificial ribonucleases derived from mono-, di- and tripeptides connected by linkers of different hydrophobicity. AB - A novel series of metal-free artificial ribonucleases (aRNases) was designed, synthesized and assessed in terms of ribonuclease activity and ability to inactivate influenza virus WSN/A33/H1N1 in vitro. The compounds were built of two short peptide fragments, which include Lys, Ser, Arg, Glu and imidazole residues in various combinations, connected by linkers of different hydrophobicity (1,12 diaminododecane or 4,9-dioxa-1,12-diaminododecane). These compounds efficiently cleaved different RNA substrates under physiological conditions at rates three to five times higher than that of artificial ribonucleases described earlier and displayed RNase A-like cleavage specificity. aRNases with the hydrophobic 1,12 diaminododecane linker displayed ribonuclease activity 3-40 times higher than aRNases with the 4,9-dioxa-1,12-diaminododecane linker. The assumed mechanism of RNA cleavage was typical for natural ribonucleases, that is, general acid-base catalysis via the formation of acid/base pairs by functional groups of amino acids present in the aRNases; the pH profile of cleavage confirmed this mechanism. The most active aRNases under study exhibited high antiviral activity and entirely inactivated influenza virus A/WSN/33/(H1N1) after a short incubation period of viral suspension under physiological conditions. PMID- 26899596 TI - Design, synthesis and biological evaluation of dinucleotide mRNA cap analog containing propargyl moiety. AB - The first example of the synthesis of new dinucleotide cap analog containing propargyl group such as m(7,3'-O-propargyl)G[5']ppp[5']G is reported. The effect of propargyl cap analog with standard cap was evaluated with respect to their capping efficiency, in vitro T7 RNA polymerase transcription efficiency, and translation activity using cultured HeLa cells. It is noteworthy that propargyl cap analog outperforms standard cap by 3.1 fold in terms of translational properties. The propargyl cap analog forms a more stable complex with translation initiation factor eIF4E based on the molecular modeling studies. PMID- 26899595 TI - A potent and selective inhibitor targeting human and murine 12/15-LOX. AB - Human reticulocyte 12/15-lipoxygenase (h12/15-LOX) is a lipid-oxidizing enzyme that can directly oxidize lipid membranes in the absence of a phospholipase, leading to a direct attack on organelles, such as the mitochondria. This cytotoxic activity of h12/15-LOX is up-regulated in neurons and endothelial cells after a stroke and thought to contribute to both neuronal cell death and blood brain barrier leakage. The discovery of inhibitors that selectively target recombinant h12/15-LOX in vitro, as well as possessing activity against the murine ortholog ex vivo, could potentially support a novel therapeutic strategy for the treatment of stroke. Herein, we report a new family of inhibitors discovered in a High Throughput Screen (HTS) that are selective and potent against recombinant h12/15-LOX and cellular mouse 12/15-LOX (m12/15-LOX). MLS000099089 (compound 99089), the parent molecule, exhibits an IC50 potency of 3.4+/-0.5 MUM against h12/15-LOX in vitro and an ex vivo IC50 potency of approximately 10 MUM in a mouse neuronal cell line, HT-22. Compound 99089 displays greater than 30-fold selectivity versus h5-LOX and COX-2, 15-fold versus h15-LOX-2 and 10-fold versus h12-LOX, when tested at 20 MUM inhibitor concentration. Steady-state inhibition kinetics reveals that the mode of inhibition of 99089 against h12/15-LOX is that of a mixed inhibitor with a Kic of 1.0+/-0.08 MUM and a Kiu of 6.0+/-3.3 MUM. These data indicate that 99089 and related derivatives may serve as a starting point for the development of anti stroke therapeutics due to their ability to selectively target h12/15-LOX in vitro and m12/15-LOX ex vivo. PMID- 26899597 TI - Flexible double-headed cytosine-linked 2'-deoxycytidine nucleotides. Synthesis, polymerase incorporation to DNA and interaction with DNA methyltransferases. AB - New types of double-headed 2'-deoxycytidine 5'-O-triphosphates (dC(XC)TPs) bearing another cytosine or 5-fluorocytosine linked through a flexible propargyl, homopropargyl or pent-1-ynyl linker to position 5 were prepared by the aqueous Sonogashira cross-coupling reactions of 5-iodo-dCTP with the corresponding (fluoro)cytosine-alkynes. The modified dC(XC)TPs were good substrates for DNA polymerases and were used for enzymatic synthesis of cytosine-functionalized DNA by primer extension or PCR. The cytosine- or fluorocytosine-linked DNA probes did not significantly inhibit DNA methyltransferases and did not cross-link to these proteins. PMID- 26899598 TI - Chemical injuries caused by hydrofluoric acid leak. PMID- 26899599 TI - An easy and noninvasive technique for harvesting split thickness skin grafts in rats. AB - Skin graft studies in rats constitute a valuable adjunct to scientific human experimentations, however the harvesting of split thickness skin graft poses a challenge to the researcher due to the presence of panniculus carnosus tissue in rat skin. This striated muscle tissue renders significant laxity and mobility to the skin layer, greatly interfering with the process of skin graft harvest. In order to fixate the rat skin and limit its flexibility various techniques and modifications have been described, which mostly rely on the use of subdermal implanted templates. These methods are therefore time consuming, with an additional exposure to surgical stress and wounds. A new and simple technique is presented which offers a rapid and reliable alternative to the existing methods of split thickness skin graft harvesting without any additional invasive procedure or extra instruments other than the researchers hands and a dermatome. PMID- 26899601 TI - Enhancement of hydrolysis of Chlorella vulgaris by hydrochloric acid. AB - Chlorella vulgaris is considered as one of the potential sources of biomass for bio-based products because it consists of large amounts of carbohydrates. In this study, hydrothermal acid hydrolysis with five different acids (hydrochloric acid, nitric acid, peracetic acid, phosphoric acid, and sulfuric acid) was carried out to produce fermentable sugars (glucose, galactose). The hydrothermal acid hydrolysis by hydrochloric acid showed the highest sugar production. C. vulgaris was hydrolyzed with various concentrations of hydrochloric acid [0.5-10 % (w/w)] and microalgal biomass [20-140 g/L (w/v)] at 121 degrees C for 20 min. Among the concentrations examined, 2 % hydrochloric acid with 100 g/L biomass yielded the highest conversion of carbohydrates (92.5 %) into reducing sugars. The hydrolysate thus produced from C. vulgaris was fermented using the yeast Brettanomyces custersii H1-603 and obtained bioethanol yield of 0.37 g/g of algal sugars. PMID- 26899602 TI - Power consumption evaluation of different fed-batch strategies for enzymatic hydrolysis of sugarcane bagasse. AB - The minimization of costs in the distillation step of lignocellulosic ethanol production requires the use of a high solids loading during the enzymatic hydrolysis to obtain a more concentrated glucose liquor. However, this increase in biomass can lead to problems including increased mass and heat transfer resistance, decreased cellulose conversion, and increased apparent viscosity with the associated increase in power consumption. The use of fed-batch operation offers a promising way to circumvent these problems. In this study, one batch and four fed-batch strategies for solids and/or enzyme feeding during the enzymatic hydrolysis of sugarcane bagasse were evaluated. Determinations of glucose concentration, power consumption, and apparent viscosity were made throughout the experiments, and the different strategies were compared in terms of energy efficiency (mass of glucose produced according to the energy consumed). The best energy efficiency was obtained for the strategy in which substrate and enzyme were added simultaneously (0.35 kg(glucose) kWh-1). This value was 52% higher than obtained in batch operation. PMID- 26899600 TI - MEGSA: A Powerful and Flexible Framework for Analyzing Mutual Exclusivity of Tumor Mutations. AB - The central challenges in tumor sequencing studies is to identify driver genes and pathways, investigate their functional relationships, and nominate drug targets. The efficiency of these analyses, particularly for infrequently mutated genes, is compromised when subjects carry different combinations of driver mutations. Mutual exclusivity analysis helps address these challenges. To identify mutually exclusive gene sets (MEGS), we developed a powerful and flexible analytic framework based on a likelihood ratio test and a model selection procedure. Extensive simulations demonstrated that our method outperformed existing methods for both statistical power and the capability of identifying the exact MEGS, particularly for highly imbalanced MEGS. Our method can be used for de novo discovery, for pathway-guided searches, or for expanding established small MEGS. We applied our method to the whole-exome sequencing data for 13 cancer types from The Cancer Genome Atlas (TCGA). We identified multiple previously unreported non-pairwise MEGS in multiple cancer types. For acute myeloid leukemia, we identified a MEGS with five genes (FLT3, IDH2, NRAS, KIT, and TP53) and a MEGS (NPM1, TP53, and RUNX1) whose mutation status was strongly associated with survival (p = 6.7 * 10(-4)). For breast cancer, we identified a significant MEGS consisting of TP53 and four infrequently mutated genes (ARID1A, AKT1, MED23, and TBL1XR1), providing support for their role as cancer drivers. PMID- 26899603 TI - Treatment of feet deformities in epidermolysis bullosa. AB - BACKGROUND: Inherited epidermolysis bullosa is a rare disease characterised by mechanical fragility of the skin when under insignificant stress. The main consequences of epidermolysis bullosa, mainly the dystrophic type, despite pseudosyndactyly, are joint contractures and deformities in hands and feet. In this study, we describe our experience treating patients suffering from epidermolysis bullosa, as far as feet deformities are concerned. METHODS: This is a retrospective analysis of a consecutive series of patients presenting feet deformities related to epidermolysis bullosa. Extension contractures of the toes, equinus and cavus deformities were treated with soft tissues surgery. RESULTS: Thirteen surgical procedures were done in six patients with feet deformities caused by epidermolysis bullosa. Of the feet operated 85.7 % extension contracture of the toes was asymptomatic at follow-up. However, 42.9 % developed hammertoe deformities. There were no recurrence or complications for other deformities. Subjectively, all patients declared themselves very satisfied with the results. CONCLUSION: Foot deformities must be treated as early as possible, due to progressive disability for walking and pain symptoms. We considered that, despite long term complications, treatment was adequate and we recommend it. Level of Evidence Level IV. PMID- 26899604 TI - Entecavir Reduces Hepatocarcinogenesis in Chronic Hepatitis B Patients. AB - Chronic hepatitis B (CHB) leads to cirrhosis and hepatocellular carcinoma (HCC). With a cohort of 1,206 CHB patients who visited Okayama University Hospital and related hospitals in 2011 and 2012, we compared the incidence rates of HCC among the patients grouped by age, hepatitis B virus (HBV) DNA, hepatitis B e antigen (HBeAg), and treatment. HCCs were observed in 115 patients with the median observation period of 1,687 days. Among the HCC patients aged > 35 years, HBV DNA > 4 log copies/mL and positive HBeAg at diagnosis (n=184), the HCC incidence rate was 8.4% at 5 years in the entecavir (ETV)-treated patients, 21.8% in the lamivudine (LVD)-treated patients, and 26.4% among the patients not treated with drugs. The cumulative HCC incidence was significantly reduced in the ETV-treated patients compared to those treated with LVD or not treated (p=0.013). Among the patients aged >35 years with HBV DNA > 4 log copies/mL and negative HBeAg (n=237), the cumulative HCC incidence was 14.6% in 5 years in ETV group and 13.9% among those not treated with a drug (p>0.05). Only small numbers of HCCs occurred in other patients. In CHB patients aged > 35 years with HBV DNA > 4 log copies/mL and positive HBeAg, ETV treatment is recommended for the suppression of HCC development. PMID- 26899605 TI - The Function of beta2-glycoprotein I in Angiogenesis and Its in Vivo Distribution in Tumor Xenografts. AB - Intact beta2-glycoprotein I (ibeta2GPI) is a glycoprotein that regulates coagulation and fibrinolysis. Nicked beta2GPI (nbeta2GPI) possesses an angiogenic property at a relatively low concentration, and an antiangiogenic property at a high concentration. Here we investigated the functions of betai 2GPI and nbeta2GPI in vascular endothelial growth factor (VEGF)-A-induced endothelial cell proliferation and tube formation. We used noninvasive PET imaging to analyze the in vivo distribution of intravenously injected beta2GPI variants in tumor lesions in mice. ibeta2GPI was incubated with plasmin to obtain nbeta2GPI, and its N terminal sequence was analyzed. nbeta2GPI had at least one other cleavage site upstream of the beta2GPI's domain V, whereas the former plasmin-cleavage site locates between K317 and T318. Both of intact and nicked beta2GPI significantly inhibited the VEGF-A-induced cell proliferation and the tube formation of human umbilical vein endothelial cells (HUVECs). PET imaging visualized considerably distributed intensities of all tested beta2GPI variants in tumor lesions of pancreatic tumor cell-xenografts. These results indicate that beta2GPI may be physiologically and pathophysiologically important in the regulation of not only coagulation and fibrinolysis, but also angiogenesis. PMID- 26899606 TI - Calcium Phosphate Composition Affects Ureteroscopic Laser Lithotripsy. AB - The effects of stone composition on transurethral lithotripsy (TUL) have not been sufficiently elucidated. The purpose of this study was to identify how calcium phosphate stone composition impacts TUL. Two hundred eighty-nine cases of semi rigid and/or flexible TUL for upper urinary tract calculi were reviewed retrospectively. Inclusion criteria were a preoperative assessment by noncontrast computed tomography (NCCT) and a stone composition analysis. Small stones and those without calcium composition were excluded. Stone core radiodensity (SCR) was measured by taking the average of the upper 3 of 5 points in the proximity of the center of the stone on NCCT. Fifty-three patients with calcium phosphate composition (CaP) and 118 patients with calcium oxalate and without phosphate composition were eligible for analysis. SCR was significantly higher in the CaP group (p<0.01). The CaP patient group needed a significantly longer operation time (p=0.014) and more laser energy (p=0.085), and tended to have a lower rate of complete lithotripsy (p=0.096) and higher incidence of postoperative pyelonephritis (p=0.181). Stones containing calcium phosphate are harder, demand more laser energy, and require a longer operating time. NCCT evaluation can estimate stone composition preoperatively, and may be a useful tool for predicting operative outcomes. PMID- 26899607 TI - A Long-term Survivor after Congenital Acute Myeloid Leukemia with t(8 ; 16)(p11 ; p13). AB - The treatment of patients with congenital leukemia is difficult and often results in a poor prognosis. We present here the case of a female child with congenital acute myeloid leukemia (AML) with t(8 ; 16) (p11 ; p13) who received chemotherapy and survived for more than 10 years without relapse. A novel MOZ-CBP chimera was found in her diagnostic sample. Although adult AML patients with MOZ-CBP have mainly been reported as having therapy-related AML and showed poor prognoses, the present case supports the idea that AML with MOZ-CBP in the pediatric population might show better prognoses. PMID- 26899608 TI - Effects of Dexmedetomidine on Serum Interleukin-6, Hemodynamic Stability, and Postoperative Pain Relief in Elderly Patients under Spinal Anesthesia. AB - The beneficial effects of dexmedetomidine (DEX) have not been extensively investigated in elderly patients receiving spinal anesthesia. This study evaluated the effects of intravenous DEX infusion on stress and hemodynamic response, as well as on postoperative analgesia in elderly patients undergoing total knee arthroplasty (TKA). We randomly allocated 45 adult patients to 3 patient groups (n=15 each): uni-saline group patients underwent unilateral TKA with saline administration, uni-DEX group patients underwent unilateral TKA with DEX administration, and bilateral-DEX group patients underwent bilateral TKA with DEX administration. Serum interleukin-6 (IL-6) levels were significantly lower in the bilateral-DEX group than in the uni-saline group 6 and 24h postoperatively, and were negatively correlated with total DEX dosage 24h postoperatively. Bradycardia occurred more frequently in the uni-DEX and bilateral-DEX groups than in the uni-saline group. The total dose of required supplementary analgesics was significantly higher in the uni-saline group than in the uni-DEX and bilateral DEX groups 6h postoperatively. The results indicate that perioperative intravenous DEX administration decreases postoperative serum IL-6 levels in patients undergoing bilateral TKA, and has a postoperative analgesic effect in patients undergoing unilateral or bilateral TKA. PMID- 26899609 TI - Importance of Milk Expression for Preterm Infants. AB - Mothers of preterm infants may find it difficult to express breast milk. There is a low breast milk rate among preterm infants at discharge at our hospital, and here we tested the hypothesis that milk expression factors were the cause of the low rate. The study subjects were born before 33 gestational weeks at our hospital between March 2005 and June 2014. Nutritional evaluation was performed at discharge and noted whether breast milk, infant formula, or a mix of the 2 was being given. We compared the group given breast milk or the mix versus the group given formula. Of the 337 infants, 40 cases were excluded. Data from 297 infants were analyzed. The mean (SD) gestational age and birth weight were 29.5 (2.4) weeks and 1,230 (391) g, respectively. At discharge, 26 (8.8% ), 102 (33.3% ), and 174 (57.9% ) infants were given breast milk, formula, and the mix, respectively. A multivariate logistic regression analysis showed that the first milk expression (h) was the risk factor for the formula group: adjusted odds ratio (95% confidence interval) 1.06 (1.02-1.09) and p=0.002. Delayed first milk expression could affect the low breast milk rate at discharge. Improvement of milk expression should be achieved to promote breastfeeding. PMID- 26899610 TI - Computer-assisted Minimally Invasive Posterior Lumbar Interbody Fusion without C arm Fluoroscopy. AB - Computer-assisted spinal surgery is becoming more common; however, this is the first technical report to describe the technique of minimally invasive spinal posterior lumbar interbody fusion (MIS-PLIF) without using C-arm fluoroscopy. The authors report 2 years of follow-up of a 49-year-old female patient with L4 degenerative spondylolisthesis. The patient suffered from low back pain and intermittent claudication for more than 6 years. The authors performed computer assisted MIS-PLIF without C-arm fluoroscopy. Instead, O-arm(r) navigation, the use of which reduces radiation exposure to patients as well as others in the operating room, was employed. Surgery was successful, and correct lumbar alignment was maintained. She had neither neurological deficits nor low back pain at her 12-month final follow-up. In conclusion, computer-assisted MIS-PLIF without C-arm fluoroscopy is a useful technique that reduces radiation exposure to the surgeon and operating room staff. PMID- 26899611 TI - Orthodontic Treatment of a Patient with Bilateral Congenitally Missing Maxillary Canines: The Effects of First Premolar Substitution on the Functional Outcome. AB - Permanent canines are thought to play a pivotal role in obtaining an ideal occlusion. Dentists occasionally encounter patients who lack canines and are therefore missing a key to harmonious guidance during functional mandibular excursions. This case report describes the substitution of maxillary first premolars for congenitally missing canines in the context of an orthodontic treatment plan. A boy, age 10 years and 11 months, with a chief complaint of crooked teeth was diagnosed with Class II division 2 malocclusion associated with a high mandibular plane angle and deep overbite. A stable occlusion with a satisfactory facial profile and functional excursions without interference were achieved after a comprehensive two-stage orthodontic treatment process. The resulting occlusion and satisfactory facial profile were maintained for 12 months. These results indicate that substituting the first premolars for the canines is an effective option in treating patients with missing canines while maintaining functional goals. PMID- 26899613 TI - Erratum. Anxiety and Feelings toward the Baby among Pregnant Women with Uterine Leiomyomas. Vol. 69, No. 6, pp 339-348. PMID- 26899612 TI - Induction S-1+Concurrent Radiotherapy Followed by Surgical Resection of Locally Advanced Non-small-cell Lung Cancer in an Elderly Patient. AB - We present the case of a 77-year-old Japanese man diagnosed with lung squamous cell carcinoma with mediastinal lymph node metastasis. He was treated with induction chemoradiotherapy for T1bN2M0 stage IIIA disease. Considering his age, we selected S-1 as the chemotherapeutic drug. Observing an objective response with no severe adverse events, we performed a left upper lobectomy with sleeve resection of the pulmonary artery. No residual tumor cells were found in the resected specimens, and no critical complication was observed in the clinical course. This case suggests that induction chemoradiotherapy using S-1 combined with concurrent radiation followed by surgery can be a therapeutic option for elderly patients with locally advanced non-small-cell lung cancer. PMID- 26899617 TI - Ambulatory Blood Pressure Monitoring: New Directions and Uncertainties Arise From the U.S. Preventive Services Task Force Recommendation on the Diagnosis of Hypertension. PMID- 26899615 TI - Herpes Mastitis: Diagnosis and Management. AB - Herpetic lesions most frequently occur on oral and genital areas. However, herpes simplex virus (HSV) can be a rare cause of breast infection. In few published articles, the route of transmission is predominantly from infant to mother. We report two cases about simultaneous mammary and extramammary (oral and genital) herpetic infection in nonlactating women. In both cases, HSV breast lesions were acquired by sexual contacts with partners who were asymptomatic HSV carriers. Through a review of literature, we highlight clinical signs for an early diagnosis. We also emphasize the advantage of the valacyclovir for treating this uncommon pathology. PMID- 26899614 TI - Long distance dispersal and vertical gene flow in the Caribbean brooding coral Porites astreoides. AB - To date, most assessments of coral connectivity have emphasized long-distance horizontal dispersal of propagules from one shallow reef to another. The extent of vertical connectivity, however, remains largely understudied. Here, we used newly-developed and existing DNA microsatellite loci for the brooding coral Porites astreoides to assess patterns of horizontal and vertical connectivity in 590 colonies collected from three depth zones (<=10 m, 15-20 m and >=25 m) at sites in Florida, Bermuda and the U.S. Virgin Islands (USVI). We also tested whether maternal transmission of algal symbionts (Symbiodinium spp.) might limit effective vertical connectivity. Overall, shallow P. astreoides exhibited high gene flow between Florida and USVI, but limited gene flow between these locations and Bermuda. In contrast, there was significant genetic differentiation by depth in Florida (Upper Keys, Lower Keys and Dry Tortugas), but not in Bermuda or USVI, despite strong patterns of depth zonation in algal symbionts at two of these locations. Together, these findings suggest that P. astreoides is effective at dispersing both horizontally and vertically despite its brooding reproductive mode and maternal transmission of algal symbionts. In addition, these findings might help explain the ecological success reported for P. astreoides in the Caribbean in recent decades. PMID- 26899618 TI - Fatal non-occlusive mesenteric ischemia and the use of propranolol in paediatric burns. AB - Abdominal complications without abdominal injury are infrequently seen in children with major burns. They are divided into those that occur early during the emergency phase of treatment and those that occur late in the course of treatment. One of the most serious late onset complications is non-occlusive mesenteric ischaemia associated with the use of vasoactive drugs. We report on 2 children who late in the course of their burn injury developed ischaemic necrosis of their entire intestine. Both were on propranolol, the administration of which was continued with even during the periods of septic shock which preceded their demise. We are of the opinion that endogenous catecholamine release during hypotensive and septic episodes in conjunction with beta-adrenergic blockage from propranolol could lead to severe splanchnic vasoconstriction from unopposed alpha adrenergic activity and hence critical circulation impairment to the bowel in the 2 children. PMID- 26899616 TI - Replication and shedding of MERS-CoV in Jamaican fruit bats (Artibeus jamaicensis). AB - The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) highlights the zoonotic potential of Betacoronaviruses. Investigations into the origin of MERS-CoV have focused on two potential reservoirs: bats and camels. Here, we investigated the role of bats as a potential reservoir for MERS-CoV. In vitro, the MERS-CoV spike glycoprotein interacted with Jamaican fruit bat (Artibeus jamaicensis) dipeptidyl peptidase 4 (DPP4) receptor and MERS-CoV replicated efficiently in Jamaican fruit bat cells, suggesting there is no restriction at the receptor or cellular level for MERS-CoV. To shed light on the intrinsic host-virus relationship, we inoculated 10 Jamaican fruit bats with MERS CoV. Although all bats showed evidence of infection, none of the bats showed clinical signs of disease. Virus shedding was detected in the respiratory and intestinal tract for up to 9 days. MERS-CoV replicated transiently in the respiratory and, to a lesser extent, the intestinal tracts and internal organs; with limited histopathological changes observed only in the lungs. Analysis of the innate gene expression in the lungs showed a moderate, transient induction of expression. Our results indicate that MERS-CoV maintains the ability to replicate in bats without clinical signs of disease, supporting the general hypothesis of bats as ancestral reservoirs for MERS-CoV. PMID- 26899620 TI - Crystal phase-controlled synthesis of rod-shaped AgInTe2 nanocrystals for in vivo imaging in the near-infrared wavelength region. AB - Rod-shaped AgInTe2 nanocrystals (NCs) exhibiting intense near-band edge photoluminescence in the near-infrared (NIR) wavelength region, were successfully prepared by the thermal reaction of metal acetates and Te precursors in 1 dodecanethiol. Increasing the reaction temperature resulted in the formation of larger AgInTe2 NCs with crystal structures varying from hexagonal to tetragonal at reaction temperatures of 280 degrees C or higher. The energy gap was increased from 1.13 to 1.20 eV with a decrease in rod width from 8.3 to 5.6 nm, accompanied by a blue shift in the photoluminescence (PL) peak wavelength from 1097 to 1033 nm. The optimal PL quantum yield was approximately 18% for AgInTe2 NCs with rod widths of 5.6 nm. The applicability of AgInTe2 NCs as a NIR-emitting material for in vivo biological imaging was examined by injecting AgInTe2 NC incorporated liposomes into the back of a C57BL/6 mouse, followed by in vivo photoluminescence imaging in the NIR region. PMID- 26899619 TI - Measurements in wound healing with observations on the effects of topical agents on full thickness dermal incised wounds. AB - INTRODUCTION: A multitude of topical wound treatments are used today. Although it is well established that the micro-environment of healing wounds can be altered to improve healing, it is difficult to measure the subtle differences in outcome where therapies are compared. METHOD: We compared wound healing properties between four different topical agents in surgically incised wounds in a pig model. The four topical agents, 5% Povidone-Iodine cream, 1% Silver Sulphadiazine, 2% Mupirocin, and 1% Silver-Sulphadiazine plus 1mg/100g recombinant-human epithelial growth factor (EGF) were randomly assigned to four test animals each. Test agents were compared to each other and to untreated controls. We investigated existing and new methodologies of measurement of wound healing: clinical and histological visual scoring systems, immuno-histochemistry, and computerized image analysis of the wounds on days 3, 7, and 28. RESULTS: All agents were found to have improved healing rates with better cellular architecture. Healing was faster, histological appearance resembled normal architecture sooner, clinical appearance improved, mitotic activity was stimulated and more collagen was deposited in comparison to the wounds with no agents. EGF-treated wounds showed an increased rate of epithelisation, but the rate of healing did not correlate well with evaluation of cosmetic outcome. CONCLUSION: Topical agents improve all aspects of wound healing. The addition of a human recombinant EGF to Silver-Sulphadiazine increases epithelial growth and amounts of collagen in the regenerating wounds at day 7. PMID- 26899621 TI - Exploring the effects of the atherosclerosis progression and the choice of affected arteries in the design of experiments with Apolipoprotein E-deficient mice. AB - The objective of this study is to explore the longitudinal progression of atherosclerosis and the correlation between methods to measure the lesion in apolipoprotein E-deficient mice. Atherosclerosis progression was assessed by measurements of foam cell-rich depositions in their proximal aortas, and/or in surgically excised arteries, to assess the histological luminal narrowing. A longitudinal study was performed by comparing the values for carotid, aorta, and femoral and iliac arteries using common histological techniques. There were no significant differences in progression between different arteries, but correlation with the classical measurement of atherosclerosis in the aortic root was poor. Each laboratory requires specific standardization. Carotid arteries were sensitive to atherosclerosis in these mice, and progression was exponential. In conclusion, morphometric data show the importance of the choice of the duration of treatment, the appropriate controls, and the age at which to begin the experiments. PMID- 26899622 TI - Sampling diverse characters improves phylogenies: Craniodental and postcranial characters of vertebrates often imply different trees. AB - Morphological cladograms of vertebrates are often inferred from greater numbers of characters describing the skull and teeth than from postcranial characters. This is either because the skull is believed to yield characters with a stronger phylogenetic signal (i.e., contain less homoplasy), because morphological variation therein is more readily atomized, or because craniodental material is more widely available (particularly in the palaeontological case). An analysis of 85 vertebrate datasets published between 2000 and 2013 confirms that craniodental characters are significantly more numerous than postcranial characters, but finds no evidence that levels of homoplasy differ in the two partitions. However, a new partition test, based on tree-to-tree distances (as measured by the Robinson Foulds metric) rather than tree length, reveals that relationships inferred from the partitions are significantly different about one time in three, much more often than expected. Such differences may reflect divergent selective pressures in different body regions, resulting in different localized patterns of homoplasy. Most systematists attempt to sample characters broadly across body regions, but this is not always possible. We conclude that trees inferred largely from either craniodental or postcranial characters in isolation may differ significantly from those that would result from a more holistic approach. We urge the latter. PMID- 26899625 TI - Copper-catalyzed three-component cascade reaction of alkynes, sulfonyl azides and simple aldehydes/ketones. AB - A copper-catalyzed dimethylzinc-promoted three-component cascade reaction of alkynes, sulfonyl azides, and simple aldehydes or ketones is described. Polysubstituted olefins were thus constructed expeditiously in a one-pot procedure under mild conditions. PMID- 26899623 TI - Association Analysis of Interleukin-17 Gene Polymorphisms with the Risk Susceptibility to Tuberculosis. AB - BACKGROUND: Recently, many institutions have investigated the associations of interleukin-17 (IL17) polymorphisms with tuberculosis (TB) susceptibility, while those results are inconsistent. The purpose of this meta-analysis is to comprehensively assess whether IL17A rs22275913, IL17F rs763780, and IL17A rs3748067 polymorphisms are correlated with TB risk. METHODS: Electronic bibliographic databases were searched for case-control studies which potentially focused on the relationship between the aforementioned polymorphisms and TB risk on October 15th, 2015. Pooled odds ratios (OR) combined with 95 % confidence intervals (CI) were employed to assess the associations. RESULTS: There was no significant association of IL-17A rs22275913 polymorphism with susceptibility to TB in Asians or Caucasians. For IL-17A rs3748067 polymorphism, significant associations were observed in Asian (T vs. C: OR 1.461, 95 % CI 1.158-1.844, P = 0.001; TT vs. CC: OR 1.871, 95 % CI 1.140-3.069, P = 0.013; TT/TC vs. CC: OR 1.392 95 % CI 1.062-1.825, P = 0.017; TT vs. TC/CC: OR 1.820, 95 % CI 1.111 2.981, P = 0.017). For IL-17F rs763780, we detected the significant associations under allele contrast, heterozygote, dominant and recessive models (C vs. T: OR 1.571, 95 % CI 1.352-1.824, P = 0.000; CT vs. TT: OR 1.624, 95 % CI 1.346-1.958, P = 0.000; CT/TT vs. TT: OR 1.639, 95 % CI 1.381-1.946, P = 0.000, respectively). The corresponding results were also detected in Asian populations (C vs. T: OR 1.068, 95 % CI 1.380-1.875, P = 0.000; CT vs. TT: OR 1.689, 95 % CI 1.390-2.053, P = 0.000; CT/TT vs. TT: OR 1.695, 95 % CI 1.420-2.023, P = 0.000), while there were no significant associations in Caucasian. CONCLUSION: IL-17F rs763780 allele C and IL-17A rs3748067 allele C may be involved in the susceptibility to TB in Asian populations. There were no significant associations between IL-17A rs22275913 polymorphism and risk of TB. PMID- 26899624 TI - Impaired Lung Mitochondrial Respiration Following Perinatal Nicotine Exposure in Rats. AB - Perinatal smoke/nicotine exposure predisposes to chronic lung disease and morbidity. Mitochondrial abnormalities may contribute as the PPARgamma pathway is involved in structural and functional airway deficits after perinatal nicotine exposure. We hypothesized perinatal nicotine exposure results in lung mitochondrial dysfunction that can be rescued by rosiglitazone (RGZ; PPARgamma receptor agonist). Sprague-Dawley dams received placebo (CON), nicotine (NIC, 1 mg kg(-1)), or NIC + RGZ (3 mg kg(-1)) daily from embryonic day 6 to postnatal day 21. Parenchymal lung (~10 mg) was taken from adult male offspring for mitochondrial assessment in situ. ADP-stimulated O2 consumption was less in NIC and NIC + RGZ compared to CON (F[2,14] = 17.8; 4.5 +/- 0.8 and 4.1 +/- 1.4 vs. 8.8 +/- 2.5 pmol s mg(-1); p < 0.05). The respiratory control ratio for ADP, an index of mitochondrial coupling, was reduced in NIC and remediated in NIC + RGZ (F[2,14] = 3.8; p < 0.05). Reduced mitochondrial oxidative capacity and abnormal coupling were evident after perinatal nicotine exposure. RGZ improved mitochondrial function through tighter coupling of oxidative phosphorylation. PMID- 26899626 TI - Three-dimensional Echocardiography of Right Ventricular Function Correlates with Severity of Pediatric Pulmonary Hypertension. AB - BACKGROUND: Right ventricular function and biomarkers of B-type natriuretic peptide (BNP) and N-Terminal pro-BNP (NT pro-BNP) are used to determine the severity of right ventricular failure and outcomes from pulmonary hypertension. Real-time three-dimensional echocardiography (3DE) is a novel quantitative measure of the right ventricle and decreases the geometric assumptions from conventional two-dimensional echocardiography (2DE). We correlated right ventricular functional measures using 2DE and single-beat 3DE with biomarkers and hemodynamics to determine the severity of pediatric pulmonary hypertension. METHODS: We retrospectively evaluated 35 patients (mean age 12.67 +/- 5.78 years) with established pulmonary hypertension who had echocardiograms and biomarkers on the same day. Ten out of 35 patients had hemodynamic evaluation within 3 days. 2DE evaluation included tricuspid annular plane systolic excursion (TAPSE), right ventricular myocardial performance index from tissue Doppler imaging (RV TDI MPI), and right ventricular fractional area change (FAC). Three-dimensional echocardiography evaluation included right ventricular ejection fraction (EF), end-systolic volume, and end-diastolic volume. The quality of the 3DE was graded as good, fair, or poor. Pearson correlation coefficients were utilized to evaluate between biomarkers and echocardiographic parameters and between hemodynamics and echocardiography. RESULTS: Three-dimensional echocardiography and FAC correlated significantly with BNP and NT pro-BNP. TAPSE and RV TDI MPI did not correlate significantly with biomarkers. 3D right ventricular EF correlated significantly with hemodynamics. Two-dimensional echocardiography did not correlate with hemodynamics. CONCLUSIONS: Single-beat 3DE is a noninvasive, feasible tool in the quantification of right ventricular function and maybe more accurate than conventional 2DE in evaluating severity of pulmonary hypertension. PMID- 26899627 TI - Pediatric diabetic retinopathy: experience of a tertiary hospital in Ethiopia. AB - BACKGROUND: Diabetic retinopathy is one of the micro vascular complications of diabetes mellitus. To date there are no studies that show the magnitude of diabetic retinopathy in the pediatric population of Ethiopia with only very few in Africa. The purpose of this study was to determine the prevalence of diabetic retinopathy in children and adolescents at a tertiary center in Ethiopia. METHODS: This cross-sectional hospital based descriptive study included children aged between 9 and 17 years attending the endocrine follow-up clinic of Tikur Anbesa Specialized Hospital. A structured questionnaire was used for evaluating sociodemographic data and information pertinent to diabetes. The prevalence of diabetic retinopathy was determined by fundus photography of each eye. RESULTS: A total of 86 patients were examined with a mean age of 13.7 (SD = 1.8) years. At onset of diabetes, 95.6% of children presented with diabetic ketoacidosis(DKA); 22 children (25.6%) had at least two episodes of DKA, and 45 children (52.3%) had poor glycemic control. Background retinopathy was present in four children (4.7%) with a mean age of 14.25 (SD = 1.89) years and two of them also had maculopathy. CONCLUSION: Although there are some methodological limitations, this study highlights the difficulties of achieving good glycemic control and the early occurrence of diabetic retinopathy in Ethiopian diabetic children. PMID- 26899628 TI - Stereoselective hydroxylation by CYP2C19 and oxidation by ADH4 in the in vitro metabolism of tivantinib. AB - 1. In prior studies, it has been shown that tivantinib is extensively metabolized in humans to many oxidative metabolites and glucuronides. In order to identify the responsible enzymes, we investigated the in vitro metabolism of tivantinib and its four major circulating metabolites. 2. The primary isoforms involved in the elimination of tivantinib were CYP2C19 and CYP3A4/5. CYP2C19 showed catalytic activity for the formation of M5 (hydroxylated metabolite), but not for M4 (a stereoisomer of M5), whereas CYP3A4/5 catalyzed the formation of both metabolites. For the elimination of M4, M5 and M8 (keto-metabolite), CYP3A4/5 was the major cytochrome P450 isoform and UGT1A9 was mainly involved in the glucuronidation of M4 and M5. 3. ADH4 was identified as one of the major alcohol dehydrogenase isoforms contributing to the formation of M6 (sequential keto metabolite of M4 and M5) and M8. The substrate preference of ADH for M4, and not M5, was observed in the formation of M6. 4. In conclusion, CYP2C19, CYP3A4/5, UGT1A9 and ADH4 were the primary drug metabolizing enzymes involved in the in vitro metabolism of tivantinib and its metabolites. The stereoselective hydroxylation by CYP2C19 and substrate stereoselectivity of ADH4-catalyzed oxidation in the in vitro metabolism of tivantinib was discovered. PMID- 26899629 TI - Effects of a broad-spectrum caspase inhibitor, Z-VAD(OMe)-FMK, on viral hemorrhagic septicemia virus (VHSV) infection-mediated apoptosis and viral replication. AB - In the development of inactivated or attenuated viral vaccines for cultured fish, viral titers harvested from the cultured cells would be the most important factor for the determination of vaccine's cost effectiveness. In this study, we hypothesized that the lengthening of cell survival time by the inhibition of apoptosis can lead to an increase of the final titer of viral hemorrhagic septicemia virus (VHSV). To test the hypothesis, we investigated the effects of a broad-spectrum caspase inhibitor, Z-VAD(OMe)-FMK, on VHSV infection-mediated apoptosis in Epithelioma papulosum cyprini (EPC) cells and on the VHSV titers. VHSV infection induced the DNA laddering in EPC cells, and the progression of DNA fragmentation was in proportion to the CPE extension. The progression of DNA fragmentation in EPC cells infected with VHSV was clearly inhibited by exposure to Z-VAD(OMe)-FMK, and the inhibition was intensified according to the increase of the inhibitor concentration. These results confirmed the previous reports that the death of host cells by VHSV infection is through apoptosis. Cells infected with a recombinant VHSV, rVHSV-DeltaNV-eGFP, that was generated from our previous study by replacement of the NV gene ORF with the enhanced green fluorescent protein (eGFP) gene ORF, showed earlier and more distinct DNA fragmentations compared to the cells infected with wild-type VHSV, suggesting the inhibitory role of the NV protein in VHSV-mediated apoptosis that was previously reported. The final viral titers in the supernatant isolated from Z-VAD(OMe)-FMK treated cells after showing an extensive CPE were significantly higher than the viral titers from cells infected with virus alone, indicating that the delay of apoptosis by Z-VAD(OMe)-FMK extended the survival time of EPC cells, which lengthen the time for VHSV replication in the cells. In conclusion, Z-VAD(OMe) FMK-mediated inhibition of apoptosis significantly increased the final titers of both wild-type VHSV and rVHSV-DeltaNV-eGFP, indicating that apoptosis inhibition can be a way to get higher titers of VHSV. PMID- 26899630 TI - Immune indices and identical functions of two prophenoloxidases from the haemolymph of green tiger shrimp Penaeus semisulcatus and its antibiofilm activity. AB - In the present study, we purified two prophenoloxidases (proPO) from haemolymph of green tiger shrimp, Penaeus semisulcatus by gel fermentation chromatography using blue Sepharose matrix. The two purified prophenoloxidase macromolecules are of about 76 and 75 kDa determined through SDS-PAGE and named as Penaeus semisulcatus prophenoloxidase I (PSproPO I) and Penaeus semisulcatus prophenoloxidase II (PSproPO II). It was further characterized by X-Ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), Circular Dichroism (CD) and High Performance Liquid Chromatography (HPLC) analysis. The purified PSproPO I and PSproPO II showed the strongest agglutination titre against human erythrocytes compared to goat RBC. The PSproPO I and PSproPO II showed phagocytic activity against yeast Saccharomyces cerevisiae and encapsulation activity against Sepharose CL 6B beads compared to CM Sepharose and Sodium alginate beads. The functional analysis of purified PSproPO I and PSproPO II showed enhanced PO activity when added with the triggering molecules such as pathogen associated molecular patterns (PAMPs), metals and chemicals. In addition, eluted fraction containing PSproPO I and PSproPO II showed antibiofilm activity against Gram positive and Gram negative bacteria. The above results concluded that no significant differences were found between the purified PSproPO I and PSproPO II immune indices and functions. This study might provide a sensitive platform to understand more about the critical roles of PSproPO I and PSproPO II in crustacean immune system. PMID- 26899631 TI - Development of a decision aid for the treatment of benign prostatic hyperplasia: A four stage method using a Delphi consensus study. AB - OBJECTIVE: To develop a web-based decision aid (DA) for the treatment of lower urinary tract symptoms due to benign prostatic hyperplasia (LUTS/BPH). METHODS: From February-September 2014 we performed a four-stage development method: 1: Two round Delphi consensus method among urologists, 2: Identifying patients' needs and expectations, 3: Development of DA content and structure, 4: Usability testing with LUTS/BPH patients. RESULTS: 1 (N=15): Dutch urologists reached consensus on 61% of the statements concerning users' criteria, decision options, structure, and medical content. 2 (N=24): Consensus was reached in 69% on statements concerning the need for improvement of information provision, the need for DA development and that the DA should clarify patients' preferences. 3: DA development based on results from stage 1 and stage 2. 4 (N=10): Pros of the DA were clear information provision, systematic design and easy to read and re-read. CONCLUSION: A LUTS/BPH DA containing VCEs(**) was developed in cooperation with urologists and patients following a structured 4 stage method and was stated to be well accepted. PRACTICE IMPLICATIONS: This method can be adopted for the development of DAs to support other medical decision issues. PMID- 26899633 TI - Practicing death. AB - This narrative describes the struggle of a primary care physician contending with the challenge of remaining committed to his patient's care despite a sense of burnout in relation to an intense period of patient deaths. The story presents two patient deaths and the physician's reflections on how he handled both cases. PMID- 26899632 TI - Health literacy and adherence to medical treatment in chronic and acute illness: A meta-analysis. AB - OBJECTIVE: To use meta-analytic techniques to assess average effect sizes in studies of: (1) the correlation between patient health literacy and both medication and non-medication adherence, and (2) the efficacy of health literacy interventions on improving health literacy and treatment adherence. METHODS: PsychINFO and PubMed databases were searched (1948-2012). A total of 220 published articles met the criteria for inclusion; effect sizes were extracted and articles were coded for moderators. RESULTS: Health literacy was positively associated with adherence (r=0.14), and this association was significantly higher among non-medication regimens and in samples with cardiovascular disease. Health literacy interventions increased both health literacy (r=0.22) and adherence outcomes (r=0.16). Moderator analyses revealed greater intervention efficacy when health literacy and adherence were assessed using subjective measures compared to objective measures. Health literacy interventions had a greater effect on adherence in samples of lower income and of racial-ethnic minority patients than in non-minority and higher income samples. CONCLUSION: This is the first study to synthesize both correlational and intervention studies examining the relationship between health literacy and adherence to both medication and non-medication regimens. IMPLICATIONS: These findings demonstrate the importance of health literacy and the efficacy of health literacy interventions especially among more vulnerable patient groups. PMID- 26899634 TI - The natural history of an umbilical cord hemangioma. AB - Umbilical cord hemangiomas are rare, and the natural history is poorly understood. We present a case where the clinical course was complicated by distal umbilical cord edema, episodes of proximal obstruction of umbilical artery blood flow, transient fetal pleural and pericardial effusions, and position-dependent abnormal fetal heart rate monitoring with periods of sustained fetal tachycardia. Delivery was performed for fetal growth restriction with abnormal fetal surveillance. This case highlights possible mechanisms for fetal decompensation as well as the importance of a multifaceted approach to the management of an umbilical cord mass using multiple tools for fetal assessment. (c) 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:455-458, 2016. PMID- 26899635 TI - Selective separation behavior of graphene flakes in interaction with halide anions in the presence of an external electric field. AB - The adsorption of halide anions in the absence, and presence, of a perpendicularly external electric field on the C54H18 graphene surface has been investigated using M06-2X/6-31G(d,p) density functional theory (DFT). The structural characteristics, charge transfer, electric surface potential (ESP) maps, equilibrium distances between ions and the graphene surface and dipole moments of the ion-graphene complexes were investigated. The optimized structures show that halide anions (F(-) and Br(-)) adsorb on the graphene surface in contrast to the chloride anion that was stabilized on the edge area of the graphene flake. To clarify this unexpected behavior, diffusion of the chloride anion on the graphene surface was analyzed. The observations suggest that the moving of the chloride halide anion between barrier energies on the graphene flake has been facilitated as a result of the applied external electric field. In addition, an effective anion-pi interaction between the fluoride anion and the graphene surface in the presence of an electric field holds out the capability of these anion-graphene complexes to design anion-selective nanoscale materials. PMID- 26899637 TI - Rapid growth of environmental research in China. PMID- 26899636 TI - Prevalence of antibodies to Rickettsia conorii in human beings and dogs from Catalonia: a 20-year perspective. AB - The incidence of Mediterranean spotted fever (MSF) in Catalonia (Spain) has decreased in the last two decades. The prevalence of antibodies to Rickettsia conorii in human beings and dogs in the region of Valles Occidental (Catalonia) was assessed by indirect immunofluorescence, and the results compared with those obtained in a similar study from 1987. Nineteen (5.0%) out of 383 human serum samples had antibodies to R. conorii. This seroprevalence was significantly lower (11.5%) (P = 0.003) than that recorded in the 1987 survey. Forty-two out (42.0%) of 100 canine serum samples had antibodies to R. conorii. A high proportion of the studied dogs (91.0%) were receiving anti-tick treatment, mainly with permethrin-imidacloprid spot-on (Advantix, Bayer, Germany). The current canine seroprevalence was not significantly different from that recorded in the 1987 survey (36.9%). In conclusion, this study shows a significant decrease in the prevalence of antibodies to R. conorii in the human population of Catalonia in the last 20 years, which corresponds with a decrease in the number of cases of MSF. We suggest that the widespread use of anti-tick treatment in dogs could limit the introduction of ticks to humans due to a reduction of infestation duration in dogs, thus contributing to the decrease in MSF incidence. PMID- 26899638 TI - Temporal variation of microbial population in a thermophilic biofilter for SO2 removal. AB - The performance of a biofilter relies on the activity of microorganisms during the gas contaminant treatment process. In this study, SO2 was treated using a laboratory-scale biofilter packed with polyurethane foam cubes (PUFC), on which thermophilic desulfurization bacteria were attached. The thermophilic biofilter effectively reduced SO2 within 10months of operation time, with a maximum elimination capacity of 48.29 g/m(3)/hr. Temporal shifts in the microbial population in the thermophilic biofilter were determined through polymerase chain reaction-denaturing gradient gel electrophoresis and deoxyribonucleic acid (DNA) sequence analysis. The substrate species and environmental conditions in the biofilter influenced the microbial population. Oxygen distribution in the PUFC was analyzed using a microelectrode. When the water-containing rate in PUFC was over 98%, the oxygen distribution presented aerobic-anoxic-aerobic states along the test route on the PUFC. The appearance of sulfate-reducing bacteria was caused by the anaerobic conditions and sulfate formation after 4months of operation. PMID- 26899639 TI - Hydroxyl carboxylate based non-phosphorus corrosion inhibition process for reclaimed water pipeline and downstream recirculating cooling water system. AB - A combined process was developed to inhibit the corrosion both in the pipeline of reclaimed water supplies (PRWS) and in downstream recirculating cooling water systems (RCWS) using the reclaimed water as makeup. Hydroxyl carboxylate-based corrosion inhibitors (e.g., gluconate, citrate, tartrate) and zinc sulfate heptahydrate, which provided Zn(2+) as a synergistic corrosion inhibition additive, were added prior to the PRWS when the phosphate (which could be utilized as a corrosion inhibitor) content in the reclaimed water was below 1.7 mg/L, and no additional corrosion inhibitors were required for the downstream RCWS. Satisfactory corrosion inhibition was achieved even if the RCWS was operated under the condition of high numbers of concentration cycles. The corrosion inhibition requirement was also met by the appropriate combination of PO4(3-) and Zn(2+) when the phosphate content in the reclaimed water was more than 1.7 mg/L. The process integrated not only water reclamation and reuse, and the operation of a highly concentrated RCWS, but also the comprehensive utilization of phosphate in reclaimed water and the application of non-phosphorus corrosion inhibitors. The proposed process reduced the operating cost of the PRWS and the RCWS, and lowered the environmental hazard caused by the excessive discharge of phosphate. Furthermore, larger amounts of water resources could be conserved as a result. PMID- 26899640 TI - Mercury in alpine fish from four rivers in the Tibetan Plateau. AB - As a global pollutant, high levels of mercury (Hg) have been found in remote ecosystem due to the long range atmospheric transport. In this study, a total of 60 fish samples were collected from four rivers across the Tibetan Plateau to study the accumulation of Hg in remote and high-altitude aquatic environment. The total Hg (THg) and methylmercury (MeHg) in fish muscles ranged from 11 to 2097 ng/g dry weight (dw) (average: 819 ng/g dw) and from 14 to 1960 ng/g dw (average: 756 ng/g dw), respectively. Significantly positive linear relationships were observed between the THg (r=0.591, p<0.01, n=36) and MeHg concentrations (r=0.473, p<0.01, n=36) with the trophic level of fish from Lhasa River, suggesting trophic transfer and biomagnification of Hg in this aquatic ecosystem. Moreover, the THg levels in fish had significantly positive correlations with the length (r=0.316, p<0.05, n=60) and weight (r=0.271, p<0.05, n=60) of fish. The high levels of Hg were attributed to the slow growth and long lifespan of the fish under this sterile and cold environment. Risk assessment revealed that the consumption of Oxygymnocypris stewartii, Schizothorax macropogon, Schizothorax waltoni, Schizopygopsis younghusbandi and Schizothorax o'connori would lead to a high exposure to MeHg. PMID- 26899641 TI - Effect of organic matter on phosphorus recovery from sewage sludge subjected to microwave hybrid pretreatment. AB - Microwave (MW) hybrid processes are able to disrupt the flocculent structure of complex waste activated sludge, and help promote the recovery of phosphorus as struvite. In this study, to optimize struvite yield, (1) the characteristics of matter released in MW-hybrid treatments were compared, including MW, MW-acid, MW alkali, MW-H2O2, and MW-H2O2-alkali. The results showed that selective release of carbon, nitrogen, phosphorus, Ca(2+), and Mg(2+) achieved by sludge pretreatment using MW-hybrid processes. MW-H2O2 is the recommended sludge pretreatment process for phosphorus recovery in the form of struvite. The ratio of Mg(2+):NH4(+) N:PO4(3-)-P was 1.2:2.9:1 in the supernatant. (2) To clarify the effects of organic matter on struvite recovery, the composition and molecular weight distribution of organic matters were analyzed. Low molecular weight COD was found to facilitate the removal rate of NH4(+)-N and PO4(3)-P via crystallization, and the amorphous struvite crystals (<1kDa) from the filtered solutions had high purity. Therefore, the present study reveals the necessity of taking into consideration the interference effect of high molecular weight organic matters during struvite crystallization from sewage sludge. PMID- 26899642 TI - Estimation of bioaccessibility and potential human health risk of mercury in Chinese patent medicines. AB - Mercury (Hg), mainly in cinnabar species, has been used in medicine for thousands of years in China, and worldwide concern has been raised on its toxicity. In this work, the amount of bioaccessible mercury in 16 Chinese patent medicines (CPMs) was measured by using an in vitro simulated digestion system, consisting of simulated gastric and intestinal fluid, to investigate the bioavailability of mercury in CPMs and evaluate its potential risk to human health. Total mercury and mercury in the gastrointestinal extracts were measured by inductively coupled plasma mass spectrometry (ICP-MS). The levels of total Hg in 16 CPMs ranged from not detected to 11.89 mg/g, with a mean value of 1.13 mg/g, while the extractable Hg ranged from not detected to 4.37 MUg/g, with a mean value of 0.42 MUg/g. Mercury bioaccessibility varied significantly in the investigated CPMs, depending on the ingredient. Compared to the CPMs without cinnabar (2.5%-30.9%), the percentage of mercury in the gastrointestinal supernatants for CPMs with cinnabar was quite a bit lower (0.037%). By comparing with the Food and Agricultural Organization/World Health Organization Joint Expert Committee on Food Additives (FAO/WHO) safety guideline, the average daily intake dose (ADD) of Hg in the medicines was then calculated to access the risk of mercury to human health from taking CPMs. PMID- 26899643 TI - Distribution and assessment of heavy metals in the surface sediment of Yellow River, China. AB - Large amounts of heavy metals discharged by industrial cities that are located along the middle reach of Yellow River, China have detrimental impacts on both the ecological environment and human health. In this study, fourteen surface sediment samples were taken in the middle reach of the Yellow River. Contents of Zn, Pb, Ni, Cu, Cr, Cd, As were measured, and the pollution status was assessed using three widely used pollution assessment methods, including the single factor index method, Nemerow pollution index method and potential ecological risk index. The concentrations of the studied heavy metals followed the order: Zn>Cr>Cu>Ni>Pb>As>Cd. Nearly 50% of sites had Cu and Cr accumulation. The concentration of Cu at the Yiluo River exceeded the secondary standard value of the Environmental quality standard for soils. Comparison of heavy metal concentrations between this study and other selected rivers indicated that Cu and Cr may be the major pollutants in our case. The single factor index indicated that many samples were at high levels of pollution for Cu and Cd; the Nemerow pollution index indicated that the Yihe River, Luohe River, Yiluo River and Huayuankou were polluted. According to the results of potential ecological risk assessment, Cd in the tributaries of Luo River, Yihe River, and Yiluo River showed high risk toward the ecosystem and human health, Cd in Huanyuankou and Cu in Yiluo River showed a middle level of risk and other samples were at a low level of risk. PMID- 26899645 TI - Variation of airborne quartz in air of Beijing during the Asia-Pacific Economic Cooperation Economic Leaders' Meeting. AB - Quartz particles are a toxic component of airborne particulate matter (PM). Quartz concentrations were analyzed by X-ray diffraction in eighty-seven airborne PM samples collected from three locations in Beijing before, during, and after the Asia-Pacific Economic Cooperation (APEC) Leaders' Meeting in 2014. The results showed that the mean concentrations of quartz in PM samples from the two urban sites were considerably higher than those from the rural site. The quartz concentrations in samples collected after the APEC meeting, when the pollution restriction lever was lifted, were higher than those in the samples collected before or during the APEC meeting. The quartz concentrations ranged from 0.97 to 13.2 MUg/m(3), which were among the highest values amid those reported from other countries. The highest quartz concentration exceeded the Californian Office of Environmental Health Hazard Assessment reference exposure level and was close to the occupational threshold limit values for occupational settings. Moreover, a correlation analysis showed that quartz concentrations were positively correlated with concentrations of pollution parameters PM10, PM2.5, SO2 and NOx, but were negatively correlated with O3 concentration. The results suggest that the airborne quartz particles may potentially pose health risks to the general population of Beijing. PMID- 26899646 TI - Effect of phosphate on heterogeneous Fenton oxidation of catechol by nano-Fe3O4 Inhibitor or stabilizer? AB - The effect of phosphate on adsorption and oxidation of catechol, 1,2 dihydroxybenzene, in a heterogeneous Fenton system was investigated. In situ attenuated total reflectance infrared spectroscopy (ATR-FTIR) was used to monitor the surface speciation at the nano-Fe3O4 catalyst surface. The presence of phosphate decreased the removal rate of catechol and the abatement of dissolved organic compounds, as well as the decomposition of H2O2. This effect of phosphate was mainly due to its strong reaction with surface sites on the iron oxide catalyst. At neutral and acid pH, phosphate could displace the adsorbed catechol from the surface of catalyst and also could compete for surface sites with H2O2. In situ IR spectra indicated the formation of iron phosphate precipitation at the catalyst surface. The iron phosphate surface species may affect the amount of iron atoms taking part in the catalytic decomposition of H2O2 and formation of hydroxyl radicals, and inhibit the catalytic ability of Fe3O4 catalyst. Therefore, phosphate ions worked as stabilizer and inhibitor in a heterogeneous Fenton reaction at the same time, in effect leading to an increase in oxidation efficiency in this study. However, before use of phosphate as pH buffer or H2O2 stabilizer in a heterogeneous Fenton system, the possible inhibitory effect of phosphate on the actual removal of organic pollutants should be fully considered. PMID- 26899644 TI - Distinct potential aerosol masses under different scenarios of transport at a suburban site of Beijing. AB - In order to evaluate the secondary aerosol formation potential at a suburban site of Beijing, in situ perturbation experiments in a potential aerosol mass (PAM) reactor were carried out in the winter of 2014. The variations of secondary aerosol formation as a function of time, OH exposure, and the concentrations of gas phase pollutants and particles were reported in this study. Two periods with distinct secondary aerosol formation potentials, marked as Period I and Period II, were identified during the observation. In Period I, the secondary aerosol formation potential was high, and correlated well to the air pollutants, i.e., SO2, NO2, and CO. The maximal secondary aerosol formation was observed with an aging time equivalent to about 3 days of atmospheric oxidation. In period II, the secondary aerosol formation potential was low, with no obvious correlation with the air pollutants. Meanwhile, the aerosol mass decreased, instead of showing a peak, with increasing aging time. Backward trajectory analysis during the two periods confirmed that the air mass in Period I was mainly from local sources, while it was attributed mostly to long distance transport in Period II. The air lost its reactivity during the long transport and the particles became highly aged, resulting in a low secondary aerosol formation potential. Our experimental results indicated that the in situ measurement of the secondary aerosol formation potential could provide important information for evaluating the contributions of local emission and long distance transport to the aerosol pollution. PMID- 26899647 TI - Layered sphere-shaped TiO2 capped with gold nanoparticles on structural defects and their catalysis of formaldehyde oxidation. AB - We describe here a one-step method for the synthesis of Au/TiO2 nanosphere materials, which were formed by layered deposition of multiple anatase TiO2 nanosheets. The Au nanoparticles were stabilized by structural defects in each TiO2 nanosheet, including crystal steps and edges, thereby fixing the Au-TiO2 perimeter interface. Reactant transfer occurred along the gaps between these TiO2 nanosheet layers and in contact with catalytically active sites at the Au-TiO2 interface. The doped Au induced the formation of oxygen vacancies in the Au-TiO2 interface. Such vacancies are essential for generating active oxygen species (*O( )) on the TiO2 surface and Ti(3+) ions in bulk TiO2. These ions can then form Ti(3+)-O(-)-Ti(4+) species, which are known to enhance the catalytic activity of formaldehyde (HCHO) oxidation. These studies on structural and oxygen vacancy defects in Au/TiO2 samples provide a theoretical foundation for the catalytic mechanism of HCHO oxidation on oxide-supported Au materials. PMID- 26899648 TI - Wastewater reclamation and reuse in China: Opportunities and challenges. AB - The growing water stress both in terms of water scarcity and quality deterioration promotes the development of reclaimed water as a new water resource use. This paper reviewed wastewater reuse practices in China, and the opportunities and challenges of expanding reclaimed water use were analyzed. Rapid urbanization with the increasing of water demand and wastewater discharge provides an opportunity for wastewater reuse. The vast amount of wastewater discharge and low reclaimed water production mean that wastewater reuse still has a great potential in China. Many environmental and economic benefits and successful reclamation technologies also provide opportunities for wastewater reuse. In addition, the overall strategy in China is also encouraging for wastewater reuse. In the beginning stage of wastewater reclamation and reuse, there are many significant challenges to expand wastewater reuse in China including slow pace in adopting urban wastewater reuse programs, the establishment of integrated water resources management framework and guidelines for wastewater reuse programs, incoherent water quality requirements, the limited commercial development of reclaimed water and the strengthening of public awareness and cooperation among stakeholders. PMID- 26899649 TI - Interfacial mechanisms of heterogeneous Fenton reactions catalyzed by iron-based materials: A review. AB - The heterogeneous Fenton reaction can generate highly reactive hydroxyl radicals (OH) from reactions between recyclable solid catalysts and H2O2 at acidic or even circumneutral pH. Hence, it can effectively oxidize refractory organics in water or soils and has become a promising environmentally friendly treatment technology. Due to the complex reaction system, the mechanism behind heterogeneous Fenton reactions remains unresolved but fascinating, and is crucial for understanding Fenton chemistry and the development and application of efficient heterogeneous Fenton technologies. Iron-based materials usually possess high catalytic activity, low cost, negligible toxicity and easy recovery, and are a superior type of heterogeneous Fenton catalysts. Therefore, this article reviews the fundamental but important interfacial mechanisms of heterogeneous Fenton reactions catalyzed by iron-based materials. OH, hydroperoxyl radicals/superoxide anions (HO2/O2(-)) and high-valent iron are the three main types of reactive oxygen species (ROS), with different oxidation reactivity and selectivity. Based on the mechanisms of ROS generation, the interfacial mechanisms of heterogeneous Fenton systems can be classified as the homogeneous Fenton mechanism induced by surface-leached iron, the heterogeneous catalysis mechanism, and the heterogeneous reaction-induced homogeneous mechanism. Different heterogeneous Fenton systems catalyzed by characteristic iron-based materials are comprehensively reviewed. Finally, related future research directions are also suggested. PMID- 26899650 TI - The molecular diversity of arbuscular mycorrhizal fungi in the arsenic mining impacted sites in Hunan Province of China. AB - Arbuscular mycorrhizal fungi (AMF) can establish a mutualistic association with most terrestrial plants even in heavy metal contaminated environments. It has been documented that high concentrations of toxic metals, such as arsenic (As) in soil could adversely affect the diversity and function of AMF. However, there are still gaps in understanding the community composition of AMF under long-term As contaminations. In the present study, six sampling sites with different As concentrations were selected in the Realgar mining area in Hunan Province of China. The AMF biodiversity in the rhizosphere soils of the dominant plant species was investigated by sequencing the nuclear small subunit ribosomal RNA (SSU rRNA) gene fragments using 454-pyrosequencing technique. A total of 11 AMF genera were identified, namely Rhizophagus, Glomus, Funneliformis, Acaulospora, Diversispora, Claroideoglomus, Scutellopora, Gigaspora, Ambispora, Praglomus, and Archaeospora, among which Glomus, Rhizophagus, and Claroideoglomus clarodeum were detected in all sampling sites, and Glomus was the dominant AMF genus in the Realgar mining area. Redundancy analysis indicated that soil pH, total As and Cd concentrations were the main factors influencing AMF community structure. There was a negative correlation between the AMF species richness and the total As concentration in the soil, but no significant correlation between the Shannon Wiener index of the AMF and plants. Our study showed that high As concentrations can exert a selective effect on the AMF populations. PMID- 26899651 TI - Performance of pond-wetland complexes as a preliminary processor of drinking water sources. AB - Shijiuyang Constructed Wetland (110 hm(2)) is a drinking water source treatment wetland with primary structural units of ponds and plant-bed/ditch systems. The wetland can process about 250,000 tonnes of source water in the Xincheng River every day and supplies raw water for Shijiuyang Drinking Water Plant. Daily data for 28 months indicated that the major water quality indexes of source water had been improved by one grade. The percentage increase for dissolved oxygen and the removal rates of ammonia nitrogen, iron and manganese were 73.63%, 38.86%, 35.64%, and 22.14% respectively. The treatment performance weight of ponds and plant-bed/ditch systems was roughly equal but they treated different pollutants preferentially. Most water quality indexes had better treatment efficacy with increasing temperature and inlet concentrations. These results revealed that the pond-wetland complexes exhibited strong buffering capacity for source water quality improvement. The treatment cost of Shijiuyang Drinking Water Plant was reduced by about 30.3%. Regional rainfall significantly determined the external river water levels and adversely deteriorated the inlet water quality, thus suggesting that the "hidden" diffuse pollution in the multitudinous stream branches as well as their catchments should be the controlling emphases for river source water protection in the future. The combination of pond and plant bed/ditch systems provides a successful paradigm for drinking water source pretreatment. Three other drinking water source treatment wetlands with ponds and plant-bed/ditch systems are in operation or construction in the stream networks of the Yangtze River Delta and more people will be benefited. PMID- 26899652 TI - Recent progress in detection of mercury using surface enhanced Raman spectroscopy -A review. AB - Concerns over exposure to mercury have motivated the exploration of cost effective, rapid, and reliable method for monitoring Hg(2+) in the environment. Recently, surface-enhanced Raman scattering (SERS) has become a promising alternative method for Hg(2+) analysis. SERS is a spectroscopic technique which combines modern laser spectroscopy with the optical properties of nano-sized noble metal structures, resulting in substantially increased Raman signals. When Hg(2+) is in a close contact with metallic nanostructures, the SERS effect provides unique structural information together with ultrasensitive detection limits. This review introduces the principles and contemporary approaches of SERS based Hg(2+) detection. In addition, the perspective and challenges are briefly discussed. PMID- 26899653 TI - Development and preliminary application of a method to assess river ecological status in the Hai River Basin, north China. AB - The river ecosystem in the Hai River Basin (HRB), an important economic region in China, is seriously degraded. With the aim of river restoration in the HRB, we developed a method to assess the river's ecological status and conducted a preliminary application of the method. The established method was a predictive model, which used macroinvertebrates as indicator organisms. The river's ecological status was determined by calculating the ratio of observed to expected values (O/E). The method included ecoregionalization according to natural factors, and the selection of reference sites based on combinations of habitat quality and macroinvertebrate community. Macroinvertebrate taxa included Insecta, Crustacea, Gastropoda, and Oligochaeta, with 39 families and 95 genera identified in the HRB. The HRB communities were dominated by pollution tolerant taxa, such as Lymnaeidae, Chironomus, Limnodrilus, Glyptotendipes, and Tubifex. The average Shannon-Wiener index was 1.40+/-0.5, indicating a low biodiversity. In the river length of 3.31*10(4) km, 55% of the sites were designated poor, with a bad ecological status. Among nine secondary river systems, Luan and Zi-ya had the best and worst river conditions, respectively. Only 17 reference site groups were selected for river management in the 41 ecoregions examined. This study lays the foundation for river restoration and related research in the HRB, and we anticipate further developments of this novel method. PMID- 26899654 TI - Copper pollution decreases the resistance of soil microbial community to subsequent dry-rewetting disturbance. AB - Dry-rewetting (DW) disturbance frequently occurs in soils due to rainfall and irrigation, and the frequency of DW cycles might exert significant influences on soil microbial communities and their mediated functions. However, how microorganisms respond to DW alternations in soils with a history of heavy metal pollution remains largely unknown. Here, soil laboratory microcosms were constructed to explore the impacts of ten DW cycles on the soil microbial communities in two contrasting soils (fluvo-aquic soil and red soil) under three copper concentrations (zero, medium and high). Results showed that the fluctuations of substrate induced respiration (SIR) decreased with repeated cycles of DW alternation. Furthermore, the resistance values of substrate induced respiration (RS-SIR) were highest in non-copper-stressed (zero) soils. Structural equation model (SEM) analysis ascertained that the shifts of bacterial communities determined the changes of RS-SIR in both soils. The rate of bacterial community variance was significantly lower in non-copper-stressed soil compared to the other two copper-stressed (medium and high) soils, which might lead to the higher RS-SIR in the fluvo-aquic soil. As for the red soil, the substantial increase of the dominant group WPS-2 after DW disturbance might result in the low RS-SIR in the high copper-stressed soil. Moreover, in both soils, the bacterial diversity was highest in non-copper-stressed soils. Our results revealed that initial copper stress could decrease the resistance of soil microbial community structure and function to subsequent DW disturbance. PMID- 26899655 TI - Development and characterization of monoclonal antibodies against human aryl hydrocarbon receptor. AB - Aryl hydrocarbon receptor (AhR), a ligand-dependent nuclear receptor, is involved in a diverse spectrum of biological and toxicological effects. Due to the lack of three dimensional (3D) crystal or nuclear magnetic resonance structure, the mechanisms of these complex effects of AhR remain to be unclear. Also, commercial monoclonal antibodies (mAbs) against human AhR protein (hAhR), as alternative immunological tools, are very limited. Thus, in order to provide more tools for further studies on hAhR, we prepared two mAbs (1D6 and 4A6) against hAhR. The two newly generated mAbs specifically bound to amino acids 484-508 (located in transcription activation domain) and amino acids 201-215 (located in Per-ARNT-Sim domain) of hAhR, respectively. These epitopes were new as compared with those of commercial mAbs. The mAbs were also characterized by enzyme-linked immunosorbent assay, western blot, immunoprecipitation and indirect immunofluorescence assay in different cell lines. The results showed that the two mAbs could recognize the linearized AhRs in six different human cell lines and a rat hepatoma cell line, as well as the hAhR with native conformations. We concluded that the newly generated mAbs could be employed in AhR-based bioassays for analysis of environmental contaminants, and held great potential for further revealing the spatial structure of AhR and its biological functions in future studies. PMID- 26899656 TI - Simultaneous denitrification and denitrifying phosphorus removal in a full-scale anoxic-oxic process without internal recycle treating low strength wastewater. AB - Performance of a full-scale anoxic-oxic activated sludge treatment plant (4.0*10(5) m(3)/day for the first-stage project) was followed during a year. The plant performed well for the removal of carbon, nitrogen and phosphorus in the process of treating domestic wastewater within a temperature range of 10.8 degrees C to 30.5 degrees C. Mass balance calculations indicated that COD utilization mainly occurred in the anoxic phase, accounting for 88.2% of total COD removal. Ammonia nitrogen removal occurred 13.71% in the anoxic zones and 78.77% in the aerobic zones. The contribution of anoxic zones to total nitrogen (TN) removal was 57.41%. Results indicated that nitrogen elimination in the oxic tanks was mainly contributed by simultaneous nitrification and denitrification (SND). The reduction of phosphorus mainly took place in the oxic zones, 61.46% of the total removal. Denitrifying phosphorus removal was achieved biologically by 11.29%. Practical experience proved that adaptability to gradually changing temperature of the microbial populations was important to maintain the plant overall stability. Sudden changes in temperature did not cause paralysis of the system just lower removal efficiency, which could be explained by functional redundancy of microorganisms that may compensate the adverse effects of temperature changes to a certain degree. Anoxic-oxic process without internal recycling has great potential to treat low strength wastewater (i.e., TN<35 mg/L) as well as reducing operation costs. PMID- 26899657 TI - Chlorination pattern effect on thermodynamic parameters and environmental degradability for C10-SCCPs: Quantum chemical calculation based on virtual combinational library. AB - Short-chain chlorinated paraffins (SCCPs) are still controversial candidates for inclusion in the Stockholm Convention. The inherent mixture nature of SCCPs makes it rather difficult to explore their environmental behaviors. A virtual molecule library of 42,720 C10-SCCP congeners covering the full structure spectrum was constructed. We explored the structural effects on the thermodynamic parameters and environmental degradability of C10-SCCPs through semi-empirical quantum chemical calculations. The thermodynamic properties were acquired using the AM1 method, and frontier molecular orbital analysis was carried out to obtain the E(HOMO), E(LUMO) and E(LUMO)-E(HOMO) for degradability exploration at the same level. The influence of the chlorination degree (N(Cl)) on the relative stability and environmental degradation was elucidated. A novel structural descriptor, MU, was proposed to measure the dispersion of the chlorine atoms within a molecule. There were significant correlations between thermodynamic values and N(Cl), while the reported N(Cl)-dependent pollution profile of C10-SCCPs in environmental samples was basically consistent with the predicted order of formation stability of C10-SCCP congeners. In addition, isomers with large MU showed higher relative stability than those with small MU. This could be further verified by the relationship between MU and the reactivity of nucleophilic substitution and OH attack respectively. The C10-SCCP congeners with less Cl substitution and lower dispersion degree are susceptible to environmental degradation via nucleophilic substitution and hydroxyl radical attack, while direct photolysis of C10-SCCP congeners cannot readily occur due to the large E(LUMO)-E(HOMO) values. The chlorination effect and the conclusions were further checked with appropriate density functional theory (DFT) calculations. PMID- 26899658 TI - Efficient treatment of azo dye containing wastewater in a hybrid acidogenic bioreactor stimulated by biocatalyzed electrolysis. AB - In this study, a novel scaled-up hybrid acidogenic bioreactor (HAB) was designed and adopted to evaluate the performance of azo dye (acid red G, ARG) containing wastewater treatment. Principally, HAB is an acidogenic bioreactor coupled with a biocatalyzed electrolysis module. The effects of hydraulic retention time (HRT) and ARG loading rate on the performance of HAB were investigated. In addition, the influent was switched from synthetic wastewater to domestic wastewater to examine the key parameters for the application of HAB. The results showed that the introduction of the biocatalyzed electrolysis module could enhance anoxic decolorization and COD (chemical oxygen demand) removal. The combined process of HAB-CASS presented superior performance compared to a control system without biocatalyzed electrolysis (AB-CASS). When the influent was switched to domestic wastewater, with an environment having more balanced nutrients and diverse organic matters, the ARG, COD and nitrogen removal efficiencies of HAB-CASS were further improved, reaching 73.3%+/-2.5%, 86.2%+/-3.8% and 93.5%+/-1.6% at HRT of 6 hr, respectively, which were much higher than those of AB-CASS (61.1%+/-4.7%, 75.4%+/-5.0% and 82.1%+/-2.1%, respectively). Moreover, larger TCV/TV (total cathode volume/total volume) for HAB led to higher current and ARG removal. The ARG removal efficiency and current at TCV/TV of 0.15 were 39.2%+/-3.7% and 28.30+/-1.48 mA, respectively. They were significantly increased to 62.1%+/-2.0% and 34.55+/-0.83 mA at TCV/TV of 0.25. These results show that HAB system could be used to effectively treat real wastewater. PMID- 26899659 TI - Modifying glass fiber surface with grafting acrylamide by UV-grafting copolymerization for preparation of glass fiber reinforced PVDF composite membrane. AB - Experimental design and response surface methodology (RSM) were used to optimize the modification of conditions for glass surface grafting with acrylamide (AM) monomer for preparation of a glass fiber reinforced poly(vinylidene fluoride) (PVDF) composite membrane (GFRP-CM). The factors considered for experimental design were the UV (ultraviolet)-irradiation time, the concentrations of the initiator and solvent, and the kinds and concentrations of the silane coupling agent. The optimum operating conditions determined were UV-irradiation time of 25 min, an initiator concentration of 0-0.25 wt.%, solvent of N-Dimethylacetamide (DMAC), and silane coupling agent KH570 with a concentration of 7 wt.%. The obtained optimal parameters were located in the valid region and the experimental confirmation tests conducted showed good accordance between predicted and experimental values. Under these optimal conditions, the water absorption of the grafted modified glass fiber was improved from 13.6% to 23%; the tensile strength was enhanced and the peeling strength of the glass fiber reinforced PVDF composite membrane was improved by 23.7% and 32.6% with an AM concentration at 1 wt.% and 2 wt.%. The surface composition and microstructure of AM grafted glass fiber were studied via several techniques including Field Emission Scanning Electron Microscopy (FESEM), Fourier transform infrared spectroscopy-attenuated total reflectance (FTIR-ATR) and energy dispersive X-ray spectroscopy (EDX). The analysis of the EDX and FTIR-ATR results confirmed that the AM was grafted to the glass fiber successfully by detecting and proving the existence of nitrogen atoms in the GFRP-CM. PMID- 26899660 TI - Chronic TCDD exposure results in the dysregulation of gene expression in splenic B-lymphocytes and in the impairments in T-cell and B-cell differentiation in mouse model. AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) exposure in humans is associated with marked immune suppressions and increased incidence of lymphoblastic diseases. To elucidate mechanisms of impairments in humoral immune responses, we used a murine model. Following a 20-week administration of low doses of TCDD, we observed severely reduced antibody titers, dramatically decreased number of splenic Th1 and Th2 cells and an increase in CD19(+) B cells. Transcriptional profiling of CD19(+) B cells showed that markers of pre-B cells were significantly elevated, indicating delayed B cell maturation. These changes in B cells were accompanied by decreases of T helper cell numbers and reduced IgM and IgG titers. A transcriptome analysis of splenic B cells followed by Ingenuity Pathway Analysis (IPA) revealed a set of differentially expressed genes known to play roles in tumorigenesis, cell-proliferation and cell-migration. The most up-regulated transcript gene was Eph receptor A2 (EphA2), a known oncogene, and the most down regulated transcript was ZBTB16 that codes for a negative transcriptional regulator important in epigenetic chromatin remodeling. IPA identified cAMP responsive element modulator (CREM) and cAMP-responsive element binding protein 1 (CREB1) as top upstream regulators. Consistently, a MAPPER promoter database analysis showed that all top dysregulated genes had CREM and/or CREB1 binding sites in their promoter regions. In summary, our data showed that chronic TCDD exposure in mice caused suppressed humoral immunity accompanied with profound dysregulation of gene expression in splenic B-lymphocytes, likely through cAMP dependent pathways. This dysregulation resulted in impairments in T-cell and B cell differentiation and activation of the tumorigenic transcription program. PMID- 26899661 TI - Urban and rural transport of semivolatile organic compounds at regional scale: A multimedia model approach. AB - Urban areas are generally regarded as major sources of some semivolatile organic compounds and other persistent organic pollutants (POPs) to the surrounding regions. Huge differences in contaminant emissions between urban and rural areas directly affect their fate in environmental media. Little is known about POPs behavior between urban and rural areas at a regional scale. A spatially resolved Berkeley-Trent-Urban-Rural Fate Model (BETR-UR) was designed by coupling land cover information to simulate the transport of POPs between urban and rural areas, and the Bohai Rim was used as a case study to estimate Polycyclic Aromatic Hydrocarbon (PAH) fate. The processes of contaminant fate including emission, inter-compartmental transfer, advection and degradation in urban and rural areas were simulated in the model. Simulated PAH concentrations in environmental media of urban and rural areas were very close to measured values. The model accuracy was highly improved, with the average absolute relative error for PAH concentrations reduced from 37% to 3% compared with unimproved model results. PAH concentrations in urban soil and air were considerably higher than those in rural areas. Sensitivity analysis showed temperature was the most influential parameter for Phen rather than for Bap, whose fate was more influenced by emission rate, compartment dimension, transport velocity and chemical persistence. Uncertainty analysis indicated modeled results in urban media had higher uncertainty than those in rural areas due to larger variations of emissions in urban areas. The differences in urban and rural areas provided us with valuable guidance on policy setting for urban-rural POP control. PMID- 26899662 TI - Performance and recent improvement in microbial fuel cells for simultaneous carbon and nitrogen removal: A review. AB - Microbial fuel cells (MFCs) have become a promising technology for wastewater treatment accompanying electricity generation. Carbon and nitrogen removal can be achieved by utilizing the electron transfer between the anode and cathode in an MFC. However, large-scale power production and high removal efficiency must be achieved at a low cost to make MFCs practical and economically competitive in the future. This article reviews the principles, feasibility and bottlenecks of MFCs for simultaneous carbon and nitrogen removal, the recent advances and prospective strategies for performance improvement, as well as the involved microbes and electron transfer mechanisms. PMID- 26899663 TI - Arsenic retention and transport behavior in the presence of typical anionic and nonionic surfactants. AB - The massive production and wide use of surfactants have resulted in a large amount of surfactant residuals being discharged into the environment, which could have an impact on arsenic behavior. In the present study, the influence of the anionic surfactant sodium dodecyl benzene sulfonate (SDBS) and nonionic surfactant polyethylene glycol octylphenyl ether (Triton X-100) on arsenic behavior was investigated in batch and column tests. The presence of SDBS and Triton X-100 reduced arsenic retention onto ferrihydrite (FH), enhanced arsenic transport through FH coated sand (FH-sand) columns and promoted arsenic release from the FH surface. With coexisting surfactants in solution, the equilibrium adsorbed amount of arsenic on FH decreased by up to 29.7% and the adsorption rate decreased by up to 52.3%. Pre-coating with surfactants caused a decrease in the adsorbed amount and adsorption rate of arsenic by up to 15.1% and 58.3%, respectively. Because of the adsorption attenuation caused by surfactants, breakthrough of As(V) and As(III) with SDBS in columns packed with FH-sand was 23.8% and 14.3% faster than that in those without SDBS, respectively. In columns packed with SDBS-coated FH-sand, transport of arsenic was enhanced to a greater extent. Breakthrough of As(V) and As(III) was 52.4% and 43.8% faster and the cumulative retention amount was 44.5% and 57.3% less than that in pure FH-sand column systems, respectively. Mobilization of arsenic by surfactants increased with the increase of the initial adsorbed amount of arsenic. The cumulative release amount of As(V) and As(III) from the packed column reached 10.8% and 36.0%, respectively. PMID- 26899664 TI - Quantifying the characteristics of particulate matters captured by urban plants using an automatic approach. AB - It is widely accepted that urban plant leaves can capture airborne particles. Previous studies on the particle capture capacity of plant leaves have mostly focused on particle mass and/or size distribution. Fewer studies, however, have examined the particle density, and the size and shape characteristics of particles, which may have important implications for evaluating the particle capture efficiency of plants, and identifying the particle sources. In addition, the role of different vegetation types is as yet unclear. Here, we chose three species of different vegetation types, and firstly applied an object-based classification approach to automatically identify the particles from scanning electron microscope (SEM) micrographs. We then quantified the particle capture efficiency, and the major sources of particles were identified. We found (1) Rosa xanthina Lindl (shrub species) had greater retention efficiency than Broussonetia papyrifera (broadleaf species) and Pinus bungeana Zucc. (coniferous species), in terms of particle number and particle area cover. (2) 97.9% of the identified particles had diameter <=10 MUm, and 67.1% of them had diameter <=2.5 MUm. 89.8% of the particles had smooth boundaries, with 23.4% of them being nearly spherical. (3) 32.4%-74.1% of the particles were generated from bare soil and construction activities, and 15.5%-23.0% were mainly from vehicle exhaust and cooking fumes. PMID- 26899665 TI - Brivaracetam: First Global Approval. AB - Brivaracetam (Briviact((r))), a 4-n-propyl analogue of levetiracetam developed by UCB Pharma, has been approved in the EU as an adjunctive therapy for the treatment of partial-onset seizures. Brivaracetam binds to synaptic vesicle glycoprotein 2a (SV2A) in the brain with greater selectivity and 15- to 30-fold higher affinity than levetiracetam, as demonstrated in preclinical models, and has demonstrated efficacy in reducing the frequency of partial onset seizures in clinical trials. This article summarizes the milestones in the development of brivaracetam leading to this first approval for use as adjunctive therapy for uncontrolled partial-onset seizures in adults with epilepsy. PMID- 26899666 TI - Associations of awareness of physical activity recommendations for health and self-reported physical activity behaviours among adult South Australians. AB - OBJECTIVES: Despite widespread media campaigns to encourage physical activity (PA), participation is poor among Australian adults. This study aimed to explore the prevalence of and relationships between awareness of PA recommendations and PA participation. DESIGN: Cross-sectional study of n=2402 South Australian adults (aged>=18 years) via a computer-assisted telephone interview. METHODS: PA recommendation awareness was determined by asking for the number of minutes of PA recommended for health benefits and whether PA is needed to make you 'puff and pant' to confer a health benefit. Respondents were defined as sufficiently active if they reported >=150min/week of PA as measured by the Active Australia Survey. RESULTS: A total of 43.0% correctly identified that 30min of PA is recommended per day (Recommendation 1) and 43.3% correctly disagreed/strongly disagreed that PA is needed to make you 'puff and pant' (Recommendation 2). Overall, 60.6% of respondents were sufficiently active. Of those who correctly identified Recommendation 1, 53.2% reported participating in sufficient PA, significantly fewer than those who did not know Recommendation 1 (69.6%) (chi(2)=64.74 (4), p<0.001). There was no difference in levels of sufficient PA between those who correctly identified Recommendation 2 and those who did not. CONCLUSIONS: There was relatively low awareness of PA recommendations among South Australian adults. More research is needed in how recommendations are promoted and how they impact PA behaviours. PA recommendations are based on the best available epidemiological evidence but largely fail to guide the choices people currently make about PA. PMID- 26899667 TI - [Acantosis nigricans in severe insulin resistance syndromes]. PMID- 26899668 TI - Targeting methionyl tRNA synthetase: design, synthesis and antibacterial activity against Clostridium difficile of novel 3-biaryl-N-benzylpropan-1-amine derivatives. AB - The synthesis of a series of benzimidazole-N-benzylpropan-1-amines and adenine-N benzylpropan-1-amines is described. Subsequent evaluation against two strains of the anaerobic bacterium Clostridium difficile was performed with three amine derivatives displaying MIC values of 16 MUg/mL. Molecular docking studies of the described amines determined that the amines interact within two active site pockets of C. difficile methionyl tRNA synthetase with methoxy substituents in the benzyl ring and an adenine biaryl moiety resulting in optimal binding interactions. PMID- 26899669 TI - Management of chronic cervical lymphadenopathy in a group of children. AB - BACKGROUND: It is important how to evaluate chronic cervical lymphadenopathies and when to perform excisional biopsy in children. We tried to analyze the usefulness of clinical and ultrasonographic findings in order to differentiate malign lymphadenopathies from benign ones. METHODS: This prospective study included 100 children who had cervical lymphadenopathies, larger than 1. 5 cm for 4 weeks duration at least. Children were between 2 and 14 years old, the mean age was 6.88 +/- 3.38 years. They were examined by clinical symptoms and ultrasonographic appearances. Persistent lymphadenopathies were evaluated by excisional biopsy. RESULTS: Cervical lymhadenopathies of 80 children with well clinical symptoms decreased and resolved within 10 weeks durations. Their ultrasonographic findings revealed regular margins, ovoid shapes and getting smaller than 1. 5 cm, The remaining 20 children persisting longer than 10 weeks at the same size, with worrisome clinical symptoms and susceptible ultrasonographic findings (round shapes, irregular margins) underwent excisional biopsy. According to the biopsy results, 5 had tubercular lymphadenopathies, 3 had Hodgkin'slenfoma, 2 had acute lymphoblastic leukemia. CONCLUSIONS: Chronic cervical lymphadenopathies can persist up to 10 weeks, althoughthey are reactive and benign. PMID- 26899670 TI - Association of healthy foods intake with anthropometric measures and blood pressure in a national sample of Iranian children and adolescents: the CASPIAN- IV study. AB - BACKGROUND: This study aims to evaluate the association of consuming healthy foods with anthropometric measures and blood pressure (BP) in a national sample of Iranian children and adolescents. METHODS: This nationwide study was conducted in 2011-2012 among 13,486 students, aged 6-18 years, selected by multistage cluster sampling from 30 provinces. Weight, height, waist circumference (WC), hip circumference (HC), wais to height ratio (WHtR), waist to hip ratio (WHR), as well as systolic and diastolic blood pressures (SBP, DBP) were measured. Healthy foods were considered as four categories including fresh fruits, dried fruits, vegetables, and dairy products. The frequency consumption of each of these foods was recorded as daily, weekly, and seldom. RESULTS: The intake of fruits was significantly associated with anthropometric indices. Moreover, a significant association was found between vegetables consumption, DBP levels, and anthropometric indices (except for WHtR and WHR). Milk consumption was significantly associated with anthropometric indices (except for WHtR and WHR). The odds of general obesity among participants who seldom consumed dried fruits was less than those who consumed daily (OR: 0.84, 95%CI: 0.74-0.96). We did not find any significant association for the frequency of fresh fruits and vegetables consumption with obesity, abdominal obesity, DBP and SBP. CONCLUSIONS: Consumption of dried fruits was associated with general obesity in children and adolescents. These results highlight the effect of dietary quality and food choices on weight control in children and adolescents. PMID- 26899671 TI - Developmental writing disorders: assess to rehabilitate. AB - BACKGROUND: Writing ability requires to use and control several processes of visual and phonological information processing and an adequate programming and coordination of motor sequences. We studied a writing precursor gesture in children with developmental dysorthography and/or developmental dysgraphia in order to point out anomalies to be treated with specific rehabilitative interventions. METHODS: Twenty-five children affected by developmental dysortography (ICD 9 CM: 315.09; ICD 10: F81.1) and/or developmental dysgraphia (ICD 9 CM: 315.2; ICD 10: F81.8) (mean age 9.1 years [range: 6.3-11.4 years]) ran a maze, project in front of them, using a wireless mouse. Data regarding angular excursions, execution times and gesture accuracy were collected and elaborated using Dartfish 6.0 software and the labyrinth generating program (PRINC), and compared with normative data previously obtained from a sample of 226 healthy children of the same age and grade. RESULTS: The comparison did not evidence significant differences regarding gesture structure (trajectories of arm segments and angular excursions of interested joints). Angular and temporal execution patterns were reached in delay in these children. No correlation was found with general cognitive and visuomotor integration skills; a deficit of visual attention was associated with an abnormal elbow range of motion. CONCLUSIONS: Although these findings need to be confirmed in larger studies, data obtained evidence that children with developmental writing disorders have a time delay in the acquisition of writing motor patterns and not an alteration of gesture structure itself. This has relevant implications for the rehabilitative approach. PMID- 26899672 TI - Cognitive phenotype and language skills in children with achondroplasia. AB - AIM: Although Achondroplasia (ACH) may not be considered a condition strictly related to neuropsychiatric problems, many children referred to paediatric neurologists and psychiatrists to undergo motor and linguistic diagnostic-rehab procedures. The purpose of this study was to delineate a characterization of language difficulties in a sample of Italian children with Achondroplasia and analyze how an untreated language disorder can develop into a learning disability. METHODS: 17 Italian children (average age of 5 years and 8 months) with a clinical diagnosis genetically confirmed of Achondroplasia were enrolled. Each child underwent a neuropsychological evaluation depending on the age, which included the following areas: intelligence, language, visual-spatial skills, memory, academic achievements, behaviour. RESULTS: Most of ACH patients showed delayed speech development milestones. Cognitive evaluation revealed average abilities. All the ACH children have received a diagnosis of language impairment (DSM-5 "The Diagnostic and Statistical Manual of Mental Disorders 5 degrees edition"): "Speech sound disorder" in the pre-school-age group, "Language disorder" with impairment of both verbal expression and verbal comprehension in the school age children. CONCLUSIONS: Several studies on general population demonstrated that children with developmental speech and language problems are at considerable risk for learning disability. Considering that in our ACH sample the language disorder has been diagnosed in all children, we expect a higher prevalence of learning disabilities in ACH than in general population. PMID- 26899673 TI - 2-(1-Pyrenyl) benzimidazole as a ratiometric and "turn-on" fluorescent probe for iron(III) ions in aqueous solution. AB - A highly selective and sensitive ratiometric and "turn-on" fluorescent probe for Fe(3+), 2-(1-pyrenyl) benzimidazole (L), was synthesized by a one-step process. In emission spectra, the relative intensity ratio of excimer to monomer fluorescence (IE450/IM387) of L increased 510-fold upon the addition of 30 equiv. of Fe(3+) with a detection limit of 0.2 MUM (11.2 ppb) in aqueous solution. Meanwhile, the fluorescence excitation spectra of L showed a fluorescent "turn on" probe for Fe(3+) with 30-fold enhancement in excitation band intensity of excimer. PMID- 26899674 TI - Self-made microextraction by packed sorbent device for the cleanup of polychlorinated biphenyls from bovine serum. AB - Microextraction by packed sorbent, a miniaturized form of the solid-phase extraction, is a new sample pretreatment technology mainly used for bioanalysis. In this work, self-made device was fabricated by packing C18 sorbent into a microinjection needle (50 MUL) and then applied for the analysis of polychlorinated biphenyls in bovine serum followed by gas chromatography with mass spectrometry determination. Compared with conventional solid-phase extraction, the developed method bears many intriguing properties such as low consumption of the sample and organic solvent, time-saving and easy operation, which are of great interest and desire for bioanalysis applications. A series of parameters that affect the analytical performance, such as the type of elution, the aspirating/dispensing cycles of sample loading and elution, washing solution, and matrix effects, was investigated in detail. Under the optimized conditions, the proposed method presented a good linearity (R >= 0.986) and satisfactory sensitivity and limits of detection (0.06-0.53 ng/mL) and quantification (0.20 1.77 ng/mL), respectively. In addition, satisfactory recoveries (60.0-91.4%) and accuracy (RSD <= 5.72%) were achieved after optimizing the conditions when applying the developed method to real sample analysis. The screening of polychlorinated biphenyls residues in bovine serum samples by the developed method demonstrated that the assay is ideally suited as a monitoring method for polychlorinated biphenyls residues in bioanalysis. PMID- 26899676 TI - Rocuronium pharmacokinetics and pharmacodynamics in the adductor pollicis and masseter muscles. AB - BACKGROUND: The aim of this study was to characterize the dose-effect relationship of rocuronium at the adductor pollicis and masseter muscles. METHODS: Ten, ASA I, adult patients, received a bolus dose of rocuronium 0.3 mg/kg during propofol based anesthesia. Train-of-four (TOF) was simultaneously monitored at the masseter and the adductor pollicis muscles until recovery. Rocuronium arterial serum concentrations were measured during 120 min. The first twitch of the TOF response was used to characterize the time-effect profile of both muscles using pharmacokinetic-pharmacodynamic analysis in NONMEM. A decrease in NONMEM objective function (?OFV) of 3.84 points for an added parameter was considered significant at the 0.05 level. RESULTS: Onset time at the masseter (mean +/- SD, 1.5 +/- 0.9 min) was faster than at the adductor pollicis (2.7 +/- 1.4 min, P < 0.05). Recovery, measured as the time to TOF ratio = 0.9 was similar between muscles 29.9 +/- 6.7 (adductor pollicis) vs. 29.3 +/- 8.1 (masseter). (P = 0.77). The estimated pharmacodynamic parameters [mean (95% CI)] of the adductor pollicis muscle and the masseter muscle were; plasma effect-site equilibration half-time (teq) 3.25 (2.34, 3.69) min vs. 2.86 (1.83, 3.29) min, (?OFV 383.665); Ce50 of 1.24 (1.13, 1.56) mg/l vs. 1.19 (1.00, 1.21) mg/l, (?OFV 184.284); Hill coefficient of 3.97 (3.82, 5.62) vs. 4.68 (3.83, 5.71), (?OFV 78.906). CONCLUSIONS: We found that the masseter muscle has faster onset of blockade and similar recovery profile than adductor pollicis muscle. These findings were best, explained by a faster plasma effect-site equilibration of the masseter muscle to rocuronium. PMID- 26899677 TI - An A-PLAuse to a new assay that unveils previously undetected alpha synucleinopathies. PMID- 26899675 TI - Xeno-sensing activity of the aryl hydrocarbon receptor in human pluripotent stem cell-derived hepatocyte-like cells. AB - Although hepatocyte-like cells derived from human pluripotent stem cells (hPSC HLCs) are considered a promising model for predicting hepatotoxicity, their application has been restricted because of the low activity of drug metabolizing enzymes (DMEs). Here we found that the low expression of xenobiotic receptors (constitutive androstane receptor, CAR; and pregnane X receptor, PXR) contributes to the low activity of DMEs in hPSC-HLCs. Most CAR- and PXR-regulated DMEs and transporters were transcriptionally down-regulated in hPSC-HLC. Transcriptional expression of CAR and PXR was highly repressed in hPSC-HLCs, whereas mRNA levels of aryl hydrocarbon receptor (AHR) were comparable to those of adult liver. Furthermore, ligand-induced transcriptional activation was observed only at AHR in hPSC-HLCs. Bisulfite sequencing analysis demonstrated that promoter hypermethylation of CAR and PXR was associated with diminished transcriptional activity in hPSC-HLCs. Treatment with AHR-selective ligands increased the transcription of AHR-dependent target genes by direct AHR-DNA binding at the xenobiotic response element. In addition, an antagonist of AHR significantly inhibited AHR-dependent target gene expression. Thus, AHR may function intrinsically as a xenosensor as well as a ligand-dependent transcription factor in hPSC-HLCs. Our results indicate that hPSC-HLCs can be used to screen toxic substances related to AHR signaling and to identify potential AHR-targeted therapeutics. PMID- 26899678 TI - Evaluation of the Goldmann-Witmer coefficient in the immunological diagnosis of ocular toxocariasis. AB - Ocular toxocariasis (OT) is a zoonotic parasitic infection mainly caused by the intraocular tissue invasion of second-stage Toxocara canis or Toxocara cati larva. Measuring specific anti-T. canis antibodies in the intraocular fluid (IF) can increase OT diagnosis accuracy using Goldmann-Witmer coefficient (GWC). However, there is no systemic evaluation of GWC application in the immunological diagnosis of OT. To assess GWC for the immunodiagnosis of ocular toxocariasis, paired IF and serum samples from 72 patients diagnosed with OT were retrospectively analyzed for specific anti-T. canis IgG by enzyme linked immunosorbent assay (ELISA). GWC values were calculated to determine intraocular specific IgG production. Clinical features and other laboratory data were recorded, and their correlations with GWC evaluated. Of the 72 OT patients, 60 (83.33%) showed intraocular specific IgG production confirmed by GWC, while intraocular nonspecific IgE production was found in 64/69 (92.75%) cases. No significant correlation was found among clinical features and IF specific IgG production. Values for peripheral blood samples were lower than those of intraocular fluid regarding OT screening, and vitreous humor samples showed increased local specific IgG and nonspecific IgE production compared with aqueous humor samples. Overall, our results indicate that GWC and intraocular IgE production have referential values in diagnosing ocular toxocariasis. PMID- 26899679 TI - Identification of novel CAP superfamily protein members of Echinococcus granulosus protoscoleces. AB - Echinoccocus granulosus is the causative agent of Cyst Echinococcosis, a zoonotic infection affecting humans and livestock representing a public health and an economic burden for several countries. Despite decades of investigation an effective vaccine still remains to be found. Parasitic cysteine-rich secretory proteins, antigen 5 and pathogenesis-related 1 proteins (CAPs) have been proposed as vaccine candidates against helmith's infection. In this work we have identified two novel proteins of this superfamily expressed at the protoescoleces larval stage named EgVAL1 and EgVAL2. The open reading frame sequences were deduced. The aminoacidic sequence was analyzed and confronted against already known vertebrate' and helminth's proteins sequences in order to infer putative functions. Immunolocalization studies were also performed. The obtained data supported by immunolocalization studies and homology models suggest that these proteins could be involved in protease activity inhibition. PMID- 26899681 TI - Phylogenetic structure of Leishmania tropica in the new endemic focus Birjand in East Iran in comparison to other Iranian endemic regions. AB - Iran has been identified being among the countries with the highest number of cutaneous leishmaniasis (CL) cases. South Khorasan province in East Iran is an emerging focus of CL. Species identification of sixty clinical samples by ITS1 PCR-RFLP presented evidence for the dominance of Leishmania tropica (90%) in this region. Analysis of the ITS1 sequence of 19 L. tropica isolates revealed seven closely related sequence types. In addition, ITS1 sequences available in GenBank from other Iranian regions were compiled for comparison with the studied isolates. Iranian L. tropica was distributed in two main clusters. All East Iranian sequence types were grouped with strains from foci from Southeast and Central regions in cluster A, showing highly similar sequences. The highest similarity was observed between most L. tropica from East and all isolates from Southeast regions and from Savojbolagh county in Central Iran. Southwest L. tropica was shown to be paraphyletic as the isolates were distributed in both clusters A and B. All Northeastern L. tropica were part of cluster B, however they showed significant heterogeneity and were distributed in different subclusters. Distribution of L. tropica populations was to some extent congruent with genetic lineages of Phlebotomus sergenti in Iran and may be an evidence for parasite-vector co-evolution. Southeast-East L. tropica was also similar to strains from Herat province in Afghanistan at the East border of Iran. This is the first comprehensive study on population structure of L. tropica in Iran that provides a guideline for appropriate sampling for further molecular based epidemiological studies. PMID- 26899680 TI - Epidemiology of brucellosis, Q Fever and Rift Valley Fever at the human and livestock interface in northern Cote d'Ivoire. AB - Northern Cote d'Ivoire is the main livestock breeding zone and has the highest livestock cross-border movements in Cote d'Ivoire. The aim of this study was to provide updated epidemiological data on three neglected zoonotic diseases, namely brucellosis, Q Fever and Rift Valley Fever (RVF). We conducted three-stage cross sectional cluster surveys in livestock and humans between 2012 and 2014 in a random selection of 63 villages and a sample of 633 cattle, 622 small ruminants and 88 people. We administered questionnaires to capture risk factors and performed serological tests including the Rose Bengal Plate Test (RBPT), Brucella spp. indirect and competitive ELISAs, Coxiella burnetii indirect ELISA and RVF competitive ELISA. The human seroprevalence for Brucella spp. was 5.3%. RBPT positive small ruminants tested negative by the indirect ELISA. The seroprevalence of Brucella spp. in cattle adjusted for clustering was 4.6%. Cattle aged 5-8 years had higher odds of seropositivity (OR=3.5) than those aged <=4years. The seropositivity in cattle was associated with having joint hygromas (OR=9), sharing the pastures with small ruminants (OR=5.8) and contact with pastoralist herds (OR=11.3). The seroprevalence of Q Fever was 13.9% in cattle, 9.4% in sheep and 12.4% in goats. The seroprevalence of RVF was 3.9% in cattle, 2.4% in sheep and 0% in goats. Seropositive ewes had greater odds (OR=4.7) of abortion than seronegative ones. In cattle, a shorter distance between the night pens and nearest permanent water bodies was a protective factor (OR=0.1). The study showed that the exposure to the three zoonoses is rather low in northern Cote d'Ivoire. Within a One Health approach, cost-benefit and cost-effectiveness of control measures should be assessed for an integrated control. PMID- 26899682 TI - Tunable Thermal Transport in Polysilsesquioxane (PSQ) Hybrid Crystals. AB - Crystalline polymers have attracted significant interest in recent years due to their enhanced mechanical and thermal properties. As one type of organic inorganic hybrid polymer crystals, polysilsesquioxane can be synthesized by large scale and inexpensive so-gel processes with two precursors. In this paper, both octylene-bridged and hexylene-bridged PSQ crystals are characterized with infrared spectroscopy and X-ray crystallography to reveal their super high crystallinity. To study the thermal transport in these unique polymer crystals, we use a suspended micro thermal device to examine their thermal properties from 20 K to 320 K, and demonstrate their tunable thermal conductivity by varying the length of alkyl chains. We also conduct non-equilibrium molecular dynamics simulations to study the phonon behaviors across the hydrogen bond interface. The simulation results demonstrate good agreement with the experimental results regarding both the value and trend of the PSQ thermal conductivity. Furthermore, from the simulation, we find that the anharmonic phonon scattering and interfacial anharmnic coupling effects across the hydrogen bond interface may explain the experimentally observed thermal properties. PMID- 26899711 TI - "Inverse" Frustrated Lewis Pairs--Activation of Dihydrogen with Organosuperbases and Moderate to Weak Lewis Acids. AB - A new approach to intermolecular frustrated Lewis pairs (FLPs) that combines readily available bulky organosuperbases with moderate to weak boron-containing Lewis acids is reported. These so-called "inverse" FLPs are demonstrated to heterolytically cleave dihydrogen, allowing for the isolation and structural characterization of various phosphonium borohydride salts; two FLPs proved to be efficient catalyst's in the metal-free hydrogenation of N-benzylidenaniline. PMID- 26899709 TI - PI3K/Akt/FoxO3a signaling mediates cardioprotection of FGF-2 against hydrogen peroxide-induced apoptosis in H9c2 cells. AB - Cardiovascular disease is a growing major global public health problem. Oxidative stress is regarded as one of the key regulators of pathological physiology, which eventually leads to cardiovascular disease. However, mechanisms by which FGF-2 rescues cells from oxidative stress damage in cardiovascular disease is not fully elucidated. Herein this study was designed to investigate the protective effects of FGF-2 in H2O2-induced apoptosis of H9c2 cardiomyocytes, as well as the possible signaling pathway involved. Apoptosis of H9c2 cardiomyocytes was induced by H2O2 and assessed using methyl thiazolyl tetrazolium assay, Hoechst, and TUNEL staining. Cells were pretreated with PI3K/Akt inhibitor LY294002 to investigate the possible PI3K/Akt pathways involved in the protection of FGF-2. The levels of p-Akt, p-FoxO3a, and Bim were detected by immunoblotting. Stimulation with H2O2 decreased the phosphorylation of Akt and FoxO3a, and induced nuclear localization of FoxO3a and apoptosis of H9c2 cells. These effects of H2O2 were abrogated by pretreatment with FGF-2. Furthermore, the protective effects of FGF-2 were abolished by PI3K/Akt inhibitor LY294002. In conclusion, our data suggest that FGF-2 protects against H2O2-induced apoptosis of H9c2 cardiomyocytes via activation of the PI3K/Akt/FoxO3a pathway. PMID- 26899712 TI - Low-grade malignant peripheral nerve sheath tumor: a report of the first case in the breast and literature review. PMID- 26899713 TI - Should we revisit the 'Age at First Drink' concept in alcohol research? PMID- 26899714 TI - Distinguishing the roles of energy funnelling and delocalization in photosynthetic light harvesting. AB - Photosynthetic complexes improve the transfer of excitation energy from peripheral antennas to reaction centers in several ways. In particular, a downward energy funnel can direct excitons in the right direction, while coherent excitonic delocalization can enhance transfer rates through the cooperative phenomenon of supertransfer. However, isolating the role of purely coherent effects is difficult because any change to the delocalization also changes the energy landscape. Here, we show that the relative importance of the two processes can be determined by comparing the natural light-harvesting apparatus with counterfactual models in which the delocalization and the energy landscape are altered. Applied to the example of purple bacteria, our approach shows that although supertransfer does enhance the rates somewhat, the energetic funnelling plays the decisive role. Because delocalization has a minor role (and is sometimes detrimental), it is most likely not adaptive, being a side-effect of the dense chlorophyll packing that evolved to increase light absorption per reaction center. PMID- 26899710 TI - Platelet protective efficacy of 3,4,5 trisubstituted isoxazole analogue by inhibiting ROS-mediated apoptosis and platelet aggregation. AB - Thrombocytopenia is a major hematological concern in oxidative stress-associated pathologies and chronic clinical disorders, where premature platelet destruction severely affects the normal functioning of thrombosis and hemostasis. In addition, frequent exposure of platelets to chemical entities and therapeutic drugs immensely contributes in the development of thrombocytopenia leading to huge platelet loss, which might be fatal sometimes. Till date, there are only few platelet protective molecules known to combat thrombocytopenia. Hence, small molecule therapeutics are extremely in need to relieve the burden on limited treatment strategies of thrombocytopenia. In this study, we have synthesized a series of novel 3,4,5 trisubstituted isoxazole derivatives, among which compound 4a [4-methoxy-N'-(5-methyl-3-phenylisoxazole-4-carbonyl) benzenesulfonohydrazide] was found to significantly ameliorate the oxidative stress-induced platelet apoptosis by restoring various apoptotic markers such as ROS content, cytosolic Ca(2+) levels, eIF2-alpha phosphorylation, mitochondrial membrane depolarization, cytochrome c release, caspase activation, PS externalization, and cytotoxicity markers. Additionally, compound 4a dose dependently inhibits collagen-induced platelet aggregation. Hence, compound 4a can be considered as a prospective molecule in the treatment regime of platelet activation and apoptosis and other clinical conditions of thrombocytopenia. Further studies might ensure the use of compound 4a as a supplementary therapeutic agent to treat, thrombosis and CVD associated complications. Over all, the study reveals a platelet protective efficacy of novel isoxazole derivative 4a with a potential to combat oxidative stress-induced platelet apoptosis. PMID- 26899715 TI - DNA double-strand break formation and repair in Tetrahymena meiosis. AB - The molecular details of meiotic recombination have been determined for a small number of model organisms. From these studies, a general picture has emerged that shows that most, if not all, recombination is initiated by a DNA double-strand break (DSB) that is repaired in a recombinogenic process using a homologous DNA strand as a template. However, the details of recombination vary between organisms, and it is unknown which variant is representative of evolutionarily primordial meiosis or most prevalent among eukaryotes. To answer these questions and to obtain a better understanding of the range of recombination processes among eukaryotes, it is important to study a variety of different organisms. Here, the ciliate Tetrahymena thermophila is introduced as a versatile meiotic model system, which has the additional bonus of having the largest phylogenetic distance to all of the eukaryotes studied to date. Studying this organism can contribute to our understanding of the conservation and diversification of meiotic recombination processes. PMID- 26899716 TI - Double Circular Stapler, or Laparoscopic Double Discoid Resection With a Circular Stapler. PMID- 26899718 TI - Partial Tubal Salvage Through Laparoscopic Neosalpingostomy in a Woman With Chronic Isolated Torsion of the Fallopian Tube. PMID- 26899717 TI - Double Circular Stapler (DCS) or Laparoscopic Double Discoid Resection with a Circular Stapler? Standardization of the Procedure's Nomenclature. PMID- 26899719 TI - Pre-packing of cost effective antibiotic cement beads for the treatment of traumatic osteomyelitis in the developing world - an in-vitro study based in Cambodia. AB - The developing world often lacks the resources to effectively treat the most serious injuries including osteomyelitis following open fractures or surgical fracture treatment. Antibiotic cement beads are a widely accepted method of delivering antibiotics locally to the infected area following trauma. This study is based in Cambodia, a low income country struggling to recover from a recent genocide. The study aims to test the effectiveness of locally made antibiotic beads and analyse their effectiveness after being gas sterilised, packaged and kept in storage Different antibiotic beads were manufactured locally using bone cement and tested against MRSA bacteria grown from a case of osteomyelitis. Each antibiotic was tested before and after a process of gas sterilisation as well as later being tested after storage in packaging up to 42 days. The gentamicin, vancomycin, amikacin and ceftriaxone beads all inhibited growth of the MRSA on the TSB and agar plates, both before and after gas sterilisation. All four antibiotics continued to show similar zones of inhibition after 42 days of storage. The results show significant promise to produce beads with locally obtainable ingredients in an austere environment and improve cost effectiveness by storing them in a sterilised condition. PMID- 26899720 TI - Identified lhb-expressing cells from medaka (Oryzias latipes) show similar Ca(2+) response to all endogenous Gnrh forms, and reveal expression of a novel fourth Gnrh receptor. AB - We have previously characterized the response to gonadotropin-releasing hormone (Gnrh) 2 in luteinizing hormone (lhb)-expressing cells from green fluorescent protein (Gfp)-transgenic medaka (Oryzias latipes), with regard to changes in the cytosolic Ca(2+) concentration. In the current study we present the corresponding responses to Gnrh1 and Gnrh3. Ca(2+) imaging revealed three response patterns to Gnrh1 and Gnrh3, one monophasic and two types of biphasic patterns. There were few significant differences in the shape of the response patterns between the three Gnrh forms, although the amplitude of the Ca(2+) signal was considerably lower for Gnrh1 and Gnrh3 than for Gnrh2, and the distribution between the two different biphasic patterns differed. The different putative Ca(2+) sources were examined by depleting intracellular Ca(2+) stores with thapsigargin, or preventing influx of extracellular Ca(2+) by either extracellular Ca(2+) depletion or the L-type Ca(2+)-channel blocker verapamil. Both Gnrh1 and 3 relied on Ca(2+) from both intracellular and extracellular sources, with some unexpected differences in the relative contribution. Furthermore, gene expression of Gnrh receptors (gnrhr) in whole pituitaries was studied during development from juvenile to adult. Only two of the four identified medaka receptors were expressed in the pituitary, gnrhr1b and gnrhr2a, with the newly discovered gnrhr2a showing the highest expression level at all stages as analyzed by quantitative PCR. While both receptors differed in expression level according to developmental stage, only the expression of gnrhr2a showed a clear-cut increase with gonadal maturation. RNA sequencing analysis of FACS-sorted Gfp-positive lhb cells revealed that both gnrhr1b and gnrhr2a were expressed in lhb-expressing cells, and confirmed the higher expression of gnrhr2a compared to gnrhr1b. These results show that although lhb-expressing gonadotropes in medaka show similar Ca(2+) response patterns to all three endogenous Gnrh forms through the activation of two different receptors, gnrhr1b and gnrhr2a, the differences observed between the Gnrh forms indicate activation of different Ca(2+) signaling pathways. PMID- 26899721 TI - Sex steroid profiles in zebra finches: Effects of reproductive state and domestication. AB - The zebra finch is a common model organism in neuroscience, endocrinology, and ethology. Zebra finches are generally considered opportunistic breeders, but the extent of their opportunism depends on the predictability of their habitat. This plasticity in the timing of breeding raises the question of how domestication, a process that increases environmental predictability, has affected their reproductive physiology. Here, we compared circulating steroid levels in various "strains" of zebra finches. In Study 1, using radioimmunoassay, we examined circulating testosterone levels in several strains of zebra finches (males and females). Subjects were wild or captive (Captive Wild-Caught, Wild-Derived, or Domesticated). In Study 2, using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we examined circulating sex steroid profiles in wild and domesticated zebra finches (males and females). In Study 1, circulating testosterone levels in males differed across strains. In Study 2, six steroids were detectable in plasma from wild zebra finches (pregnenolone, progesterone, dehydroepiandrosterone (DHEA), testosterone, androsterone, and 5alpha-dihydrotestosterone (5alpha-DHT)). Only pregnenolone and progesterone levels changed across reproductive states in wild finches. Compared to wild zebra finches, domesticated zebra finches had elevated levels of circulating pregnenolone, progesterone, DHEA, testosterone, androstenedione, and androsterone. These data suggest that domestication has profoundly altered the endocrinology of this common model organism. These results have implications for interpreting studies of domesticated zebra finches, as well as studies of other domesticated species. PMID- 26899722 TI - Expression of regulatory neuropeptides in the hypothalamus of red deer (Cervus elaphus) reveals anomalous relationships in the seasonal control of appetite and reproduction. AB - Red deer are seasonal with respect to reproduction and food intake, so we tested the hypothesis that their brains would show seasonal changes in numbers of cells containing hypothalamic neuropeptides that regulate these functions. We examined the brains of male and female deer in non-breeding and breeding seasons to quantify the production of kisspeptin, gonadotropin inhibitory hormone (GnIH), neuropeptide Y (NPY) and gamma-melanocyte stimulating hormone (gamma-MSH - an index of pro-opiomelanocortin production), using immunohistochemistry. These neuropeptides are likely to be involved in the regulation of reproductive function and appetite. During the annual breeding season there were more cells producing kisspeptin in the arcuate nucleus of the hypothalamus than during the non-breeding season in males and females whereas there was no seasonal difference in the expression of GnIH. There were more cells producing the appetite stimulating peptide, NPY, in the arcuate/median eminence regions of the hypothalamus of females during the non-breeding season whereas the levels of an appetite suppressing peptide, gamma-MSH, were highest in the breeding season. Male deer brains exhibited the converse, with NPY cell numbers highest in the breeding season and gamma-MSH levels highest in the non-breeding season. These results support a role for kisspeptin as an important stimulatory regulator of seasonal breeding in deer, as in other species, but suggest a lack of involvement of GnIH in the seasonality of reproduction in deer. In the case of appetite regulation, the pattern exhibited by females for NPY and gamma-MSH was as expected for the breeding and non-breeding seasons, based on previous studies of these peptides in sheep and the seasonal cycle of appetite reported for various species of deer. An inverse result in male deer most probably reflects the response of appetite regulating cells to negative energy balance during the mating season. Differences between the sexes in the seasonal changes in appetite regulating peptide cells of the hypothalamus present an interesting model for future studies. PMID- 26899723 TI - The use of energy devices for thyroid surgical procedures. Harmonic Focus versus Biclamp 150. AB - BACKGROUND: Thyroidectomy is the most frequently performed endocrine surgery, and in recent years, the surgical instruments and techniques used in this surgery have greatly evolved. New devices are created to facilitate dissection, haemostasis increasing the intraoperative cost. MATERIAL AND METHOD: We prospectively examined patients undergoing to traditional thyroidectomy using reusable vs disposable devices (BiClamp 150, ERBE (r) - group A vs. Harmonic Focus, ETHICON(r) - group B). The patients were treated for benign and malignant diseases from two experienced surgeons. The two groups were separated based on age, sex, skin-to-skin operative time, the number of parathyroid glands identified by the surgeon during the operation, preand post-operative serum calcium levels evaluated with PTH until 24 hours after surgery, the mean hospital stay, the evaluation of the content of the drainages at 6 hours and 24 hours, and the thyroid gland volume calculated via ultrasound preoperatively. The patients were asked to complete a form at 24 hours post-op to self-evaluate dysphagia to liquids and pain on a scale from 0 to 10. RESULTS: The patients analysed were 80 pts. Analysis of the data showed no significant differences between the groups with respect to age, (p = 0:48), or gender, 9 males and 31 females in group A and 8 males and 32 females in group B.The thyroid volume (in ml), calculated on the basis of preoperative ultrasonography, was 43.89 +/- 37.10 in group A vs. 54.54 +/- 51.92 in group B (p = 0.35). The skin-to-skin operative time was equal to 50.16 +/- 10.43 min.vs. 52.39 +/- 11:54 min.(p = 0.36) in groups A and B, respectively. No statistically significant differences in pre e postoperative calcium levels. The amount of drainage at 6 hours after surgery was 16.63 +/- 15.24ml. in group A and 23.72 +/- 21.93ml. in group B (p = 0.07). At 24 hours after surgery, the amount was 57.84 +/- 32.56ml. in group A and 66.79 +/- 39.94ml. in group B (p = 0.28). For group A and group B, we analysed dysphagia for liquids on a scale from 0 to 10 (4.5 +/- 2.35 vs. 4.18 +/- 2.4, p = 0.48, respectively), alterations in patients' tone of voice (1.97 +/- 2.51 vs. 1.43 +/- 0:48, p = 0.29, respectively), and postoperative pain at 24 hours after surgery (2.76 +/- 1.99 vs. 2.68 +/- 2.12, p = 0.87, respectively). The average cost for group A was equal to ? 25 * 40 = 1000 vs. ? 450 * 40 = 18000 for Group B. The hospital stay in days was equal to 1.70 +/- 0.46 (Group A) vs. 1.66 +/- 0.53 (Group B) (p = 0.69). CONCLUSIONS: One limitation of the current study is its small sample size. Both devices are effective and safe for total thyroidectomy because they have similar effects on the operative time, postoperative bleeding and patient outcomes in endocrine experienced surgical team. On the other hand, in a time of the spending review and the standardisation of surgical techniques to ensure the highest quality of services offered, the BiClamp is a viable alternative tool with a high security standard and low cost that offers significant savings to the health care system. KEY WORDS: Energy devices, Health care, Thyroidectomy. PMID- 26899724 TI - Reality Monitoring and Metamemory in Adults with Autism Spectrum Conditions. AB - Studies of reality monitoring (RM) often implicate medial prefrontal cortex (mPFC) in distinguishing internal and external information, a region linked to autism-related deficits in social and self-referential information processing, executive function, and memory. This study used two RM conditions (self-other; perceived-imagined) to investigate RM and metamemory in adults with autism. The autism group showed a deficit in RM, which did not differ across source conditions, and both groups exhibited a self-encoding benefit on recognition and source memory. Metamemory for perceived-imagined information, but not for self other information, was significantly lower in the autism group. Therefore, reality monitoring and metamemory, sensitive to mPFC function, appear impaired in autism, highlighting a difficulty in remembering and monitoring internal and external details of past events. PMID- 26899726 TI - CdS-Nanowires Flexible Photo-detector with Ag-Nanowires Electrode Based on Non transfer Process. AB - In this study, UV-visible flexible resistivity-type photo-detectors were demonstrated with CdS-nanowires (NWs) percolation network channel and Ag-NWs percolation network electrode. The devices were fabricated on Mixed Cellulose Esters (MCE) membrane using a lithographic filtration method combined with a facile non-transfer process. The photo-detectors demonstrated strong adhesion, fast response time, fast decay time, and high photo sensitivity. The high performance could be attributed to the high quality single crystalline CdS-NWs, encapsulation of NWs in MCE matrix and excellent interconnection of the NWs. Furthermore, the sensing performance was maintained even the device was bent at an angle of 90 degrees . This research may pave the way for the facile fabrication of flexible photo-detectors with high performances. PMID- 26899727 TI - New Quality Measure Core Sets Provide Continuity for Measuring Quality Improvement: Concerns Raised About Conflicting BP Measures. PMID- 26899725 TI - Widespread White Matter Differences in Children and Adolescents with Autism Spectrum Disorder. AB - Diffusion tensor imaging studies show white matter (WM) abnormalities in children with autism spectrum disorder (ASD). However, investigations are often limited by small samples, particularly problematic given the heterogeneity of ASD. We explored WM using DTI in a large sample of 130 children and adolescents (7-15 years) with and without ASD, whether age-related changes differed between ASD and control groups, and the relation between DTI measures and ASD symptomatology. Reduced fractional anisotropy and axial diffusivity were observed in ASD in numerous WM tracts, including the corpus callosum and thalamocortical fibres tracts crucial for interhemispheric connectivity and higher order information processing. Widespread WM compromise in ASD is consistent with the view that ASD is a disorder of generalized complex information processing. PMID- 26899728 TI - Optimized determination of elastic constants of crystals and their uncertainties from surface Brillouin scattering. AB - Surface Brillouin scattering of light allows the angular-dependent velocities of Rayleigh surface acoustic waves (SAW), pseudo-SAW and longitudinal lateral waves (L) on the surface of an opaque crystal to be measured, and the elastic constants thereby determined. Closed form expressions exist for the surface wave velocities in high symmetry directions on crystallographic symmetry planes, and these have been exploited in the past for obtaining the values of the elastic constants. This paper describes a procedure for obtaining an optimized set of elastic constants from SAW, pseudo-SAW and L velocities measured in arbitrary directions in the (001) and (110) surfaces of cubic crystals. It does so by affecting a linearization of the numerically determined angular-dependent SAW and pseudo-SAW velocities near the best fit, and using analytic expressions for the L velocity. The method also generates covariance ellipsoids, from which the uncertainties in the determined values of the elastic constants can be read off. The method is illustrated using surface Brillouin scattering data to obtain the room temperature elastic constants C11, C12 and C44 of the cubic crystals VC0.75 and Rh3Nb. PMID- 26899730 TI - Tumor vasculogenic mimicry predicts poor prognosis in cancer patients: a meta analysis. AB - BACKGROUND: Vasculogenic mimicry (VM) is the formation of vascular channels by tumor cells or tumor cell-derived, trans-differentiated cells in highly aggressive, solid tumors. However, the disease features and prognostic value of VM for overall survival of cancer patients remain controversial. METHOD: To systematically investigate the roles of VM in cancer progression and its prognostic values, we performed a meta-analysis based on 36 studies (33 eligible articles) including 3609 patients. The pooled hazard ratios (HRs) with 95 % confidence intervals (95 % CIs) were used to assess the relationship between VM and overall survival in cancer patients. RESULTS: Vasculogenic mimicry was significantly associated with cancer differentiation, lymph node metastasis, distant metastasis, and TNM stage. The prognostic value of VM was significant in overall survival (HR 2.16; 95 % CI 1.98-2.38; P < 0.001). Analyses stratified by confounders, such as cancer type, ethnicity, VM detection methods, sample size, and Newcastle-Ottawa quality score, found similar significant results. CONCLUSIONS: The presence of VM predicts poorer survival outcomes in cancer patients. PMID- 26899729 TI - Effects of Nrf2 silencing on oxidative stress-associated intestinal carcinogenesis in mice. AB - To assess the risk of colorectal cancer in humans with inactivation of NRF2, Nrf2 proficient (Nrf2(+/+) ) and -deficient (Nrf2(-/-) ) mice were exposed to potassium bromate (KBrO3 ) at concentrations of 750 or 1500 ppm for 52 weeks. Neoplastic proliferative lesions were observed in the small intestine and exhibited accumulations of beta-catenin and cyclin D1. The lesions had characteristics similar to those in experimental models of human hereditary colorectal cancer. An additional 13-week study was performed to examine the role of Nrf2 in the effects of oxidative stress. Significant increase in combined incidences of preneoplastic and neoplastic lesions in Nrf2(-/-) mice administered high-dose KBrO3 . In the short-term study, although 8-hydroxydeoxyguanosine (8 OHdG) levels in the epithelial DNA of Nrf2(-/-) mice at the high dose were significantly lower than those of the corresponding Nrf2(+/+) mice, the difference was very small. mRNA levels of Nrf2-regulated genes were increased in Nrf2(+/+) mice. Overexpression of cyclooxygenase 2 (COX2) and increased numbers of proliferating cell nuclear antigen (PCNA)-positive cells in the jejunal crypts were observed in Nrf2(-/-) mice administered high-dose KBrO3 . Overall, these data suggested that individuals having single-nucleotide polymorphisms in NRF2 may have a risk of colorectal cancer to some extent. PMID- 26899731 TI - A group of patients with Marfan's syndrome, who have finger and toe contractures, displays tendons' alterations upon an ultrasound examination: are these features common among classical Marfan patients? AB - The involvement of the musculoskeletal system with other mild pleiotropic manifestations represents a clinical criterion, called "systemic features," to d iagnose Marfan's syndrome. We aimed to investigate the features of the hands and feet redressable contractures present in a group of Marfan patients. In 13 patients with previously diagnosed Marfan's syndrome, an accurate clinical examination was performed. In particular the characterization of the musculoskeletal system by visual analogic scale to measure muscle pain (VAS) and muscle strength (MRC system) was carried out; the Beighton scale score was used to evaluate the articular hypermobility. Ultrasound examination (US) was performed to detect deep-superficial flexor tendons and extensor tendons of both hands, and the short and long flexor and extensor tendons of the fingers and toes in static and dynamic positions. The ImageJ program was adopted to measure a profile of tendon echo-intensity. A reduction of the thickness of all tendons was detected by US in our patients; the VAS and Beighton scale scores were in normal ranges. The profile of tendon echo-intensity showed different textural details in all Marfan patients. This study provides evidence for other contractures' localization, and for altered findings of the tendons in patients with Marfan syndrome and finger/toe contractures. These changes may be associated with structural modifications in connective tissue. PMID- 26899732 TI - Graphene growth on Ge(100)/Si(100) substrates by CVD method. AB - The successful integration of graphene into microelectronic devices is strongly dependent on the availability of direct deposition processes, which can provide uniform, large area and high quality graphene on nonmetallic substrates. As of today the dominant technology is based on Si and obtaining graphene with Si is treated as the most advantageous solution. However, the formation of carbide during the growth process makes manufacturing graphene on Si wafers extremely challenging. To overcome these difficulties and reach the set goals, we proposed growth of high quality graphene layers by the CVD method on Ge(100)/Si(100) wafers. In addition, a stochastic model was applied in order to describe the graphene growth process on the Ge(100)/Si(100) substrate and to determine the direction of further processes. As a result, high quality graphene was grown, which was proved by Raman spectroscopy results, showing uniform monolayer films with FWHM of the 2D band of 32 cm(-1). PMID- 26899733 TI - Editorial: Effective and Promising Treatments for Neurological Disorders and Cancer. PMID- 26899734 TI - Indole-3-acetic acid biosynthetic pathways in the basidiomycetous yeast Rhodosporidium paludigenum. AB - Microorganisms produce plant growth regulators, such as auxins, cytokinins and gibberellins, to promote plant growth. Auxins are a group of compounds with an indole ring that have a positive effect on plant growth. Indole-3-acetic acid (IAA) is a plant growth hormone classified as an indole derivative of the auxin family. IAA biosynthesis pathways have been reported and widely studied in several groups of bacteria. Only a few studies on IAA biosynthesis pathways have been conducted in yeast. This study aimed to investigate IAA biosynthesis pathways in a basidiomycetous yeast (Rhodosporidium paludigenum DMKU-RP301). Investigations were performed both with and without a tryptophan supplement. Indole compound intermediates were detected by gas chromatography-mass spectrometry. Indole-3-lactic acid and indole-3-ethanol were found as a result of the enzymatic reduction of indole-3-pyruvic acid and indole-3-acetaldehyde, in IAA biosynthesis via an indole-3-pyruvic acid pathway. In addition, we also found indole-3-pyruvic acid in culture supernatants determined by high-performance liquid chromatography. Identification of tryptophan aminotransferase activity supports indole-3-pyruvic acid-routed IAA biosynthesis in R. paludigenum DMKU RP301. We hence concluded that R. paludigenum DMKU-RP301 produces IAA through an indole-3-pyruvic acid pathway. PMID- 26899736 TI - Interannual variability of average minimum temperatures derived from tree rings in the mid-Qinling Mountains, China, for the past 138 years. AB - In this study, spruce tree rings from the southern slope of mid-Qinling Mountains were adopted to investigate the characteristics of average minimum temperatures during the past 138 years. Analysis showed that the interannual variability in radial growth of trees was positively correlated with the interannual variability of average minimum temperatures from previous December to current September (VTM DS) in the study area during 1955-2010 AD. Based on the correlation analysis, the VTM DS were reconstructed for 1876-2013 AD with an explained variance of 42.5 % for the calibration period. Among the 22 dramatic changing years, extreme changes occurred more times when it was cooling, while the warming was comparatively gentle. Both the 10-year filtering of VTM DS series and the frequency of occurrences for those dramatic changing years showed a relatively stationary variation after the early 1950s. Over the last five decades, the accumulated VTM DS series showed an obvious warming trend, and the increase of the minimum temperature had contributed to the regional warming. The comparison of VTM DS and the dryness/wetness indices generally reflected cold-wet and warm-dry climate conditions in the study area. Significant positive correlations between the reconstructed VTM DS and the gridded minimum temperature indicated a regional representative of the temperature reconstruction, and positive correlations between VTM DS and sea surface temperature (SST) of the Indian Ocean and western Pacific regions suggested a possible linkage between the VTM DS variations and the Asian summer monsoon. Synchronous fluctuations in three tree-ring study series and connections of VTM DS with Arctic oscillation (AO) and El Nino Southern Oscillation (ENSO) activities suggested that the minimum temperature variations in the TTH area responded sensitively to large-scale climate fluctuations and were the results of atmosphere-ocean interactions. PMID- 26899737 TI - Plain water consumption in relation to energy intake and diet quality among US adults, 2005-2012. AB - OBJECTIVE: The present study examined plain water consumption in relation to energy intake and diet quality among US adults. METHODS: A nationally representative sample of 18 311 adults aged >=18 years, from the National Health and Nutrition Examination Survey 2005-2012, was analysed. The first-difference estimator approach addressed confounding bias from time-invariant unobservables (e.g. eating habits, taste preferences) by using within-individual variations in diet and plain water consumption between two nonconsecutive 24-h dietary recalls. RESULTS: One percentage point increase in the proportion of daily plain water in total dietary water consumption was associated with a reduction in mean (95% confidence interval) daily total energy intake of 8.58 (7.87-9.29) kcal, energy intake from sugar-sweetened beverages of 1.43 (1.27-1.59) kcal, energy intake from discretionary foods of 0.88 (0.44-1.32) kcal, total fat intake of 0.21 (0.17 0.25) g, saturated fat intake of 0.07 (0.06-0.09) g, sugar intake of 0.74 (0.67 0.82) g, sodium intake of 9.80 (8.20-11.39) mg and cholesterol intake of 0.88 (0.64-1.13) g. The effects of plain water intake on diet were similar across race/ethnicity, education attainment, income level and body weight status, whereas they were larger among males and young/middle-aged adults than among females and older adults, respectively. Daily overall diet quality measured by the Healthy Eating Index-2010 was not found to be associated with the proportion of daily plain water in total dietary water consumption. CONCLUSIONS: Promoting plain water intake could be a useful public health strategy for reducing energy and targeted nutrient consumption in US adults, which warrants confirmation in future controlled interventions. PMID- 26899735 TI - There's Something Wrong with my MAM; the ER-Mitochondria Axis and Neurodegenerative Diseases. AB - Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis with associated frontotemporal dementia (ALS/FTD) are major neurodegenerative diseases for which there are no cures. All are characterised by damage to several seemingly disparate cellular processes. The broad nature of this damage makes understanding pathogenic mechanisms and devising new treatments difficult. Can the different damaged functions be linked together in a common disease pathway and which damaged function should be targeted for therapy? Many functions damaged in neurodegenerative diseases are regulated by communications that mitochondria make with a specialised region of the endoplasmic reticulum (ER; mitochondria-associated ER membranes or 'MAM'). Moreover, several recent studies have shown that disturbances to ER-mitochondria contacts occur in neurodegenerative diseases. Here, we review these findings. PMID- 26899738 TI - Tall Grass Invasion After Grassland Abandonment Influences the Availability of Palatable Plants for Wild Herbivores: Insight into the Conservation of the Apennine Chamois Rupicapra pyrenaica ornata. AB - Invasion of the tall grass Brachypodium genuense was observed in an area of the central Apennines (Italy) where the population size of Apennine chamois (Rupicapra pyrenaica ornata) was in strong decline. Since this dominant tall grass threatens biodiversity and forage quality, our hypothesis was that B. genuense abundance influenced that of palatable species for the chamois, depending on their functional traits and distribution patterns. Our sampling design used plots of 10 * 10 m and 1 * 1 m to investigate the plant community level and fine-scale interactions. We analyzed data using correlation, generalized linear models, and redundancy analyses. We found that B. genuense can reach high abundance values on the deepest soils. Its high cover value influences plant community composition by competitive exclusion of subordinate species and suppression of functional features because of temporal or spatial niche overlap. This leads to low cover of palatable species at a fine scale, and to poor pasture quality for chamois at a wider scale. Therefore, we postulated that B. genuense invasion, enhanced by long-term grazing cessation, may reduce the availability of palatable plants for Apennine chamois, especially below the potential timberline (1900-2000 m a.s.l.). The high abundance of B. genuense may amplify the effect of other negative factors, such as competition with red deer (Cervus elaphus) and climate change, in restricting the suitable habitat of the Apennine chamois to the higher sectors of the central Apennines. Thus, we suggested that B. genuense spread should be monitored carefully and plans to control its invasion should be implemented. PMID- 26899739 TI - Autophagy-Modulated Human Bone Marrow-Derived Mesenchymal Stem Cells Accelerate Liver Restoration in Mouse Models of Acute Liver Failure. AB - BACKGROUND: Mesenchymal stem cells (MSCs) have been recently received increasing attention for cell-based therapy, especially in regenerative medicine. However, the low survival rate of these cells restricts their therapeutic applications. It is hypothesized that autophagy might play an important role in cellular homeostasis and survival. This study aims to investigate the regenerative potentials of autophagy-modulated MSCs for the treatment of acute liver failure (ALF) in mice. METHODS: ALF was induced in mice by intraperitoneal injection of 1.5 ml/kg carbon tetrachloride. Mice were intravenously infused with MSCs, which were suppressed in their autophagy pathway. Blood and liver samples were collected at different intervals (24, 48 and 72 h) after the transplantation of MSCs. Both the liver enzymes and tissue necrosis levels were evaluated using biochemical and histopathological assessments. The survival rate of the transplanted mice was also recorded during one week. RESULTS: Biochemical and pathological results indicated that 1.5 ml/kg carbon tetrachloride induces ALF in mice. A significant reduction of liver enzymes and necrosis score were observed in autophagy-modulated MSC-transplanted mice compared to sham (with no cell therapy) after 24 h. After 72 h, liver enzymes reached their normal levels in mice transplanted with autophagy-suppressed MSCs. Interestingly, normal histology without necrosis was also observed. CONCLUSION: Autophagy suppression in MSCs ameliorates their liver regeneration potentials due to paracrine effects and might be suggested as a new strategy for the improvement of cell therapy in ALF. PMID- 26899740 TI - The influence of perceived family support on post surgery recovery. AB - The objective of this work was to investigate the possible relationship between perceived family support, levels of cortisol and post surgery recovery. The study sample comprised 42 patients that were due to undergo open cholecystectomy surgery in a Regional Health Authority Reference Centre of the Autonomous Community of Extremadura in Spain. The FACES-II questionnaire was used for the evaluation of perceived family support and to measure the three fundamental dimensions of perceived family behaviour: cohesion, adaptability and family type. The day before surgery, a sample of saliva was taken from each subject in order to determine the level of cortisol. Results showed a clear relationship between family support and recovery. Patients with higher scores on the Cohesion Scale demonstrated better post surgery recovery (F = 8.8; gl = 40; p = .005). A relationship between levels of cortisol, perceived family support and recovery was also revealed. Patients with lower scores on the Cohesion scale and higher cortisol levels demonstrated poorer post surgery recovery (F = 10.96; gl = 40; p = .006). These results are coherent with other studies that have highlighted the beneficial effects of perceived family support on mental and physical health. PMID- 26899741 TI - Parent knowledge of children's sleep: A systematic review. AB - We completed a systematic review of literature related to parent knowledge of children's sleep, to determine how much parents know about typical child sleep and symptoms related to sleep problems in childhood and how parent knowledge has been assessed. We also examined whether relationships have been reported between parent knowledge of children's sleep, parent education, child sleep problems, sleep duration, and sleep hygiene. An extensive literature search of five electronic databases was conducted, and of 615 articles identified, eight met inclusion criteria for review: four descriptive studies and four educational interventions. These studies varied considerably in the number of items included in scales, the specific content measured, the response scales used, and the populations included, limiting the conclusions that could be drawn across studies. In general, parent knowledge of child sleep was poor. Greater accuracy was reported for items pertaining to healthy sleep practices at sleep onset and daytime symptoms, in comparison with items pertaining to child sleep problems during the night. More knowledgeable parents were more likely to report that their children exhibited healthy sleep practices; associations with sleep duration were mixed. Small interventions demonstrated an increase in parental knowledge in the short-term, but effects were not maintained at follow-up. Future work is needed to clarify relations between parental knowledge and child sleep, and to design and evaluate effective methods of promoting education about child sleep in a range of parent populations. The further development of validated tools to assess parent knowledge of child sleep will be required to underpin this work. PMID- 26899742 TI - Sleep and emotion regulation: An organizing, integrative review. AB - A growing body of research suggests that disrupted sleep is a robust risk and maintenance factor for a range of psychiatric conditions. One explanatory mechanism linking sleep and psychological health is emotion regulation. However, numerous components embedded within this construct create both conceptual and empirical challenges to the study of emotion regulation. These challenges are reflected in most sleep-emotion research by way of poor delineation of constructs and insufficient distinction among emotional processes. Most notably, a majority of research has focused on emotions generated as a consequence of inadequate sleep rather than underlying regulatory processes that may alter these experiences. The current review utilizes the process model of emotion regulation as an organizing framework for examining the impact of sleep upon various aspects of emotional experiences. Evidence is provided for maladaptive changes in emotion at multiple stages of the emotion generation and regulation process. We conclude with a call for experimental research designed to clearly explicate which points in the emotion regulation process appear most vulnerable to sleep loss as well as longitudinal studies to follow these processes in relation to the development of psychopathological conditions. PMID- 26899744 TI - It Is Time to Leave the Wilderness: A Commentary on Valencia et al.'s "Program Director Survey: Attitudes Regarding Child Neurology Training". PMID- 26899743 TI - Single-Walled Carbon Nanotubes Inhibit the Cytochrome P450 Enzyme, CYP3A4. AB - We report a detailed computational and experimental study of the interaction of single-walled carbon nanotubes (SWCNTs) with the drug-metabolizing cytochrome P450 enzyme, CYP3A4. Dose-dependent inhibition of CYP3A4-mediated conversion of the model compound, testosterone, to its major metabolite, 6beta-hydroxy testosterone was noted. Evidence for a direct interaction between SWCNTs and CYP3A4 was also provided. The inhibition of enzyme activity was alleviated when SWCNTs were pre-coated with bovine serum albumin. Furthermore, covalent functionalization of SWCNTs with polyethylene glycol (PEG) chains mitigated the inhibition of CYP3A4 enzymatic activity. Molecular dynamics simulations suggested that inhibition of the catalytic activity of CYP3A4 is mainly due to blocking of the exit channel for substrates/products through a complex binding mechanism. This work suggests that SWCNTs could interfere with metabolism of drugs and other xenobiotics and provides a molecular mechanism for this toxicity. Our study also suggests means to reduce this toxicity, eg., by surface modification. PMID- 26899745 TI - Similar rebleeding rate in 3-day and 7-day intravenous ceftriaxone prophylaxis for patients with acute variceal bleeding. AB - BACKGROUND/PURPOSE: Although prophylactic antibiotics have been recommended for cirrhotic patients with upper gastrointestinal bleeding, the duration of its use remains an inconclusive issue. We designed this study to investigate the duration of antibiotic prophylaxis for cirrhotic patients with acute esophageal variceal bleeding. METHODS: We enrolled those patients suffering from acute esophageal variceal bleeding and receiving band ligation. They were randomly allocated to two groups to receive prophylactic antibiotics; Group I: receiving intravenous ceftriaxone 500 mg every 12 hours for 3 days, and Group II: same regimen for 7 days. We used rebleeding rate within 14 days as the primary end point and also evaluated the survival rate within 28 days and the amount of transfusion during admission. RESULTS: There were 38 patients in Group I and 33 patients in Group II that completed the study course for analysis. Overall, there was no significant difference in the baseline characteristics between these two groups. There were three patients both in Group I and Group II who developed rebleeding within 14 days (8% vs. 9%, p > 0.99). There was also no difference between Group I and Group II in transfusion amount (2.71 +/- 2.84 units vs. 3.18 +/- 4.07, p = 0.839) and survival rate in 28 days (100 vs. 97%, p = 0.465). CONCLUSION: Our small scale study demonstrated that there was no difference in the rebleeding rate between 3-day and 7-day ceftriaxone prophylaxis for cirrhotic patients with acute esophageal variceal bleeding. There was also no difference in 28 day survival rate between these two groups. PMID- 26899746 TI - The pharmacology of effort-related choice behavior: Dopamine, depression, and individual differences. AB - This review paper is focused upon the involvement of mesolimbic dopamine (DA) and related brain systems in effort-based processes. Interference with DA transmission affects instrumental behavior in a manner that interacts with the response requirements of the task, such that rats with impaired DA transmission show a heightened sensitivity to ratio requirements. Impaired DA transmission also affects effort-related choice behavior, which is assessed by tasks that offer a choice between a preferred reinforcer that has a high work requirement vs. less preferred reinforcer that can be obtained with minimal effort. Rats and mice with impaired DA transmission reallocate instrumental behavior away from food-reinforced tasks with high response costs, and show increased selection of low reinforcement/low cost options. Tests of effort-related choice have been developed into models of pathological symptoms of motivation that are seen in disorders such as depression and schizophrenia. These models are being employed to explore the effects of conditions associated with various psychopathologies, and to assess drugs for their potential utility as treatments for effort-related symptoms. Studies of the pharmacology of effort-based choice may contribute to the development of treatments for symptoms such as psychomotor slowing, fatigue or anergia, which are seen in depression and other disorders. PMID- 26899747 TI - Resistant Hypertension and the Pivotal Role for Mineralocorticoid Receptor Antagonists: A Clinical Update 2016. AB - True resistant hypertension must be distinguished from apparent resistant hypertension, of which important causes include medication nonadherence, illicit drug use, and alcoholism. Ambulatory blood pressure monitoring should be considered to rule out white coat hypertension. The pathogenesis is multifactorial, but the 2 pivotal factors include volume excess and the myriad effects of aldosterone. Aldosterone increases vascular tone because of endothelial dysfunction and enhances the pressor response to catecholamines. It also plays a crucial role in vascular remodeling of small and large arteries. Aldosterone also promotes collagen synthesis, which leads to increased arterial stiffness and elevation of blood pressure. Because aldosterone has been demonstrated to modulate baroreflex resetting, in cases of severe hypertension, there would be fewer compensatory mechanisms available to offset the blood pressure elevation. PMID- 26899748 TI - The 'Normal' Heart: Fascicular Ventricular Tachycardia. PMID- 26899749 TI - Grill-Cleaning Wire Brush Bristle Ingestion: Two Cases and Review of Literature with Focus on Diagnostic Approach. PMID- 26899750 TI - Keep Your Eyes Peeled: Chemosis and Proptosis from Relapsed Leukemia. PMID- 26899752 TI - Does Long-Term Furosemide Therapy Cause Thiamine Deficiency in Patients with Heart Failure? A Focused Review. AB - Diuretic therapy is a cornerstone in the management of heart failure. Most studies assessing body thiamine status have reported variable degrees of thiamine deficiency in patients with heart failure, particularly those treated chronically with high doses of furosemide. Thiamine deficiency in patients with heart failure seems predominantly to be due to increased urine volume and urinary flow rate. There is also evidence that furosemide may directly inhibit thiamine uptake at the cellular level. Limited data suggest that thiamine supplementation is capable of increasing left ventricular ejection fraction and improving functional capacity in patients with heart failure and a reduced left ventricular ejection fraction who were treated with diuretics (predominantly furosemide). Therefore, it may be reasonable to provide such patients with thiamine supplementation during heart failure exacerbations. PMID- 26899751 TI - Changes in Lipid Profile of Obese Patients Following Contemporary Bariatric Surgery: A Meta-Analysis. AB - BACKGROUND: Although metabolic surgery was originally performed to treat hypercholesterolemia, the effects of contemporary bariatric surgery on serum lipids have not been systematically characterized. METHODS: MEDLINE, EMBASE, and Cochrane databases were searched for studies with >= 20 obese adults undergoing bariatric surgery (Roux-en-Y gastric bypass [RYGBP], adjustable gastric banding, biliopancreatic diversion [BPD], or sleeve gastrectomy). The primary outcome was change in lipids from baseline to 1 year after surgery. The search yielded 178 studies with 25,189 subjects (preoperative body mass index 45.5 +/- 4.8 kg/m(2)) and 47,779 patient-years of follow-up. RESULTS: In patients undergoing any bariatric surgery, compared with baseline, there were significant reductions in total cholesterol (TC; -28.5mg/dL), low-density lipoprotein cholesterol (LDL-C; 22.0 mg/dL), triglycerides (-61.6 mg/dL), and a significant increase in high density lipoprotein cholesterol (6.9 mg/dL) at 1 year (P < .00001 for all). The magnitude of this change was significantly greater than that seen in nonsurgical control patients (eg LDL-C; -22.0 mg/dL vs -4.3 mg/dL). When assessed separately, the magnitude of changes varied greatly by surgical type (Pinteraction < .00001; eg, LDL-C: BPD -42.5 mg/dL, RYGBP -24.7 mg/dL, adjustable gastric banding -8.8 mg/dL, sleeve gastrectomy -7.9 mg/dL). In the cases of adjustable gastric banding (TC and LDL-C) and sleeve gastrectomy (LDL-C), the response at 1 year following surgery was not significantly different from nonsurgical control patients. CONCLUSIONS: Contemporary bariatric surgical techniques produce significant improvements in serum lipids, but changes vary widely, likely due to anatomic alterations unique to each procedure. These differences may be relevant in deciding the most appropriate technique for a given patient. PMID- 26899754 TI - Progressive Collapse of the Thoracic Cage. PMID- 26899753 TI - Healthy Lifestyle and Functional Outcomes from Stroke in Women. AB - PURPOSE: While a healthy lifestyle has been associated with reduced risk of developing ischemic stroke, less is known about its effect on stroke severity. METHODS: We performed a prospective cohort study among 37,634 women without stroke or missing risk factor data at baseline. The healthy lifestyle index was composed of smoking, physical activity, body mass index, alcohol consumption, and diet (range 0-20, with 20 representing healthiest lifestyle). Possible functional outcomes were no stroke or stroke with modified Rankin Scale score of 0-1 (mild), 2-3 (moderate), or 4-6 (severe). Multinomial logistic regression was used to analyze the association between healthy lifestyle and functional outcomes from stroke. RESULTS: Over 17.2 years of follow-up, 867 total strokes were confirmed. Compared with the lowest category (0-4), the highest category (17-20) was associated with reductions in risk of total stroke with mild (odds ratio [OR] 0.43; 95% confidence interval [CI], 0.20-0.90), moderate (OR 0.53; 95% CI, 0.27 1.06), and severe (OR 0.48; 95% CI, 0.20-1.18) functional outcomes. Even a modest healthy lifestyle index (5-8 points) was associated with significant decreases in total stroke with severe and moderate functional outcomes. Similar results were seen for ischemic but not hemorrhagic strokes. CONCLUSIONS: Highest vs lowest scores on the healthy lifestyle index were associated with reductions in risk of total and ischemic strokes with mild, moderate, and severe functional outcomes among women. The evidence that even modest healthy lifestyle index scores reduced risks of total and ischemic stroke with moderate and severe functional outcomes suggests modest lifestyle changes may reduce risk of disabling stroke events. PMID- 26899755 TI - The Impact of Aging and Medical Status on Dysgeusia. AB - Disorders of taste and smell can cause an aversion to food in a sick patient and therefore affect his/her ability to maintain optimal nutrition. This can lead to a reduced level of strength, muscle mass, function, and quality of life. Additionally, reduced ability to differentiate between various intensities or concentrations of a tastant can result in increased intake of salt and sugar and exacerbation of chronic diseases such as heart failure and diabetes. These implications can be heightened in the elderly, who are particularly frail and are challenged by polypharmacy and multiple comorbid conditions. In this article, we will review the prevalence, etiology, and management of taste disorders. Additionally, we will review the association between taste and smell disorders and how disorders of smell can affect perception of taste. PMID- 26899756 TI - The Prognostic Impact of Tumor Volume in Patients with Clinical Stage IA Non Small Cell Lung Cancer. AB - INTRODUCTION: Tumor volume promises to be an important factor for predicting the prognosis of patients with non-small cell lung cancer (NSCLC). METHODS: A total of 255 patients who underwent curative surgical resection for clinical stage IA NSCLC were included. We performed semiautomated measurement of the whole tumor volume and the volume of the solid part (referred to as the solid part volume) from a volumetric analysis of chest three-dimensional computed tomography scans using the SYNAPSE VINCENT imaging software program (Fujifilm Medical, Tokyo, Japan). We evaluated the relationships among tumor size, tumor volume, and survival. RESULTS: The mean whole tumor size, the ratio of the maximum diameter of consolidation to the maximum tumor diameter (CTR), the whole tumor volume, and the solid part volume were 20 mm (range 0-30 mm), 0.84 (range 0-1.0), 3080 mm(3) (range 123-17509 mm(3)), and 2032 mm(3) (0-12466 mm(3)), respectively. The receiver operating characteristic area under the curve for the whole tumor size, CTR, whole tumor volume, and solid part volume used to identify recurrence were 0.60, 0.68, 0.58, and 0.69, respectively. A univariate analysis revealed that the whole tumor size, CTR, whole tumor volume, and solid part volume were associated with disease-free survival (DFS). A multivariate analysis of these factors identified the solid part volume to be the only independent factor for the prediction of DFS. CONCLUSIONS: The whole tumor volume and the solid part volume were associated with DFS. In particular, the solid part volume was a very useful factor for predicting prognosis in clinical stage IA NSCLC. PMID- 26899757 TI - Economic Analysis of First-Line Treatment with Erlotinib in an EGFR-Mutated Population with Advanced NSCLC. AB - INTRODUCTION: The cost-effectiveness of first-line tyrosine kinase inhibitor therapy in epidermal growth factor receptor gene (EGFR)-mutated advanced-stage non-small cell lung cancer (NSCLC) is poorly documented. We therefore conducted a cost-effectiveness analysis of first-line treatment with erlotinib versus standard chemotherapy in European patients with advanced-stage EGFR-mutated NSCLC who were enrolled in the European Erlotinib versus Chemotherapy trial. METHODS: The European Erlotinib versus Chemotherapy study was a multicenter, open-label, randomized phase III trial performed mainly in Spain, France, and Italy. We based our economic analysis on clinical data and data on resource consumption (drugs, drug administration, adverse events, and second-line treatments) collected during this trial. Utility values were derived from the literature. Incremental cost effectiveness ratios were calculated for the first-line treatment phase and for the overall strategy from the perspective of the three participating countries. Sensitivity analyses were performed by selecting the main cost drivers. RESULTS: Compared with standard first-line chemotherapy, the first-line treatment with erlotinib was cost saving (?7807, ?17,311, and ?19,364 for Spain, Italy and France, respectively) and yielded a gain of 0.117 quality-adjusted life-years. A probabilistic sensitivity analysis indicated that, given a willingness to pay at least ?90,000 for 1 quality-adjusted life-year, the probability that a strategy of first-line erlotinib would be cost-effective was 100% in France, 100% in Italy, and 99.8% in Spain. CONCLUSION: This economic analysis shows that first line treatment with erlotinib, versus standard chemotherapy, is a dominant strategy for EGFR-mutated advanced-stage NSCLC in three European countries. PMID- 26899758 TI - Pulmonary Hydatid Cyst Mimicking a Lung Cancer. PMID- 26899760 TI - Marmoset cytochrome P450 2J2 mainly expressed in small intestines and livers effectively metabolizes human P450 2J2 probe substrates, astemizole and terfenadine. AB - 1. Common marmoset (Callithrix jacchus), a New World Monkey, has potential to be a useful animal model in preclinical studies. However, drug metabolizing properties have not been fully understood due to insufficient information on cytochrome P450 (P450), major drug metabolizing enzymes. 2. Marmoset P450 2J2 cDNA was isolated from marmoset livers. The deduced amino acid sequence showed a high-sequence identity (91%) with cynomolgus monkey and human P450 2J2 enzymes. A phylogenetic tree revealed that marmoset P450 2J2 was evolutionarily closer to cynomolgus monkey and human P450 2J2 enzymes, than P450 2J forms in pigs, rabbits, rats or mice. 3. Marmoset P450 2J2 mRNA was abundantly expressed in the small intestine and liver, and to a lesser extent in the brain, lung and kidney. Immunoblot analysis also showed expression of marmoset P450 2J2 protein in the small intestine and liver. 4. Enzyme assays using marmoset P450 2J2 protein heterologously expressed in Escherichia coli indicated that marmoset P450 2J2 effectively catalyzed astemizole O-demethylation and terfenadine t-butyl hydroxylation, similar to human and cynomolgus monkey P450 2J2 enzymes. 5. These results suggest the functional characteristics of P450 2J2 enzymes are similar among marmosets, cynomolgus monkeys and humans. PMID- 26899761 TI - Erratum: Nanoscale visualization of functional adhesion/excitability nodes at the intercalated disc. PMID- 26899759 TI - Combined Pan-HER and ALK/ROS1/MET Inhibition with Dacomitinib and Crizotinib in Advanced Non-Small Cell Lung Cancer: Results of a Phase I Study. AB - INTRODUCTION: This phase I study investigated the activity of the irreversible pan-human epidermal growth factor receptor inhibitor dacomitinib in combination with the mesenchymal-epithelial transition factor/anaplastic lymphoma kinase/ROS proto-oncogene 1, receptor tyrosine kinase inhibitor crizotinib in advanced non small cell lung cancer. METHODS: Patients with progression after at least one line of chemotherapy or targeted therapy received dacomitinib once daily and crizotinib once daily or twice daily, with doses escalated until intolerable toxicity; the expansion cohorts received the maximum tolerated dose of the combination. The primary objective was to define the recommended phase II dose; secondary objectives included assessment of safety and activity of the combination in epidermal growth factor receptor inhibitor-resistant patients and correlation with tumor biomarkers. RESULTS: Seventy patients were treated in the dose-escalation (n = 33) and expansion phases (n = 37), with the maximum tolerated dose defined as dacomitinib, 30 mg once daily, plus crizotinib, 200 mg twice daily. Grade 3 or 4 treatment-related adverse events were reported in 43% of patients: the most common were diarrhea (16%), rash (7%), and fatigue (6%). There were 16 deaths; none were considered treatment related. One patient (1%) had a partial response; 46% had stable disease. Most of the tumor samples analyzed had activating epidermal growth factor receptor gene (EGFR) mutations (18 of 20 [90%]); 50% (10 of 20) had a concurrent resistance mutation. Only one sample showed MMNG HOS Transforming gene (MET) amplification (the patient had progressive disease), whereas 59% (13 of 22) and 47% (14 of 30) had high levels of expression of epidermal growth factor receptor and mesenchymal-epithelial transition factor on the basis of H-scores, respectively. There was no apparent association between biomarker expression and antitumor activity. CONCLUSION: The combination of dacomitinib and crizotinib showed limited antitumor activity in patients with advanced non-small cell lung cancer and was associated with substantial toxicity. PMID- 26899762 TI - Novel agonists of free fatty acid receptor 1 (GPR40) based on 3-(1,3,4-thiadiazol 2-yl)propanoic acid scaffold. AB - 1,3,4-Thiadiazole was explored as a more polar, heterocyclic replacement for the phenyl ring in the 3-arylpropionic acid pharmacophore present in the majority of GPR40 agonists. Out of 13 compounds synthesized using a flexible, three-step protocol (involving no chromatographic purification), four compounds were confirmed to activate the target in micromolar concentration range. While the potency of the series should be subject of further optimization, the remarkable aqueous solubility and microsomal stability observed for the lead compound (8g) apparently attests to this new scaffold's high promise in the GPR40 agonist field. PMID- 26899763 TI - HER-2, ER, PR status concordance in primary breast cancer and corresponding metastatic lesion in lymph node in Chinese women. AB - AIMS AND BACKGROUND: To compare the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) in the primary site and the metastatic lesion of lymph nodes in invasive breast cancer for investigating whether the expression of these biomarkers in the primary site could act as a surrogate to the lymphatic metastatic lesion in the same patient. METHODS: In lymphatic metastatic lesion and corresponding primary lesion of 107 cases of invasive breast cancer, ER and PR statuses were assessed by immunohistochemistry (IHC). HER-2 expression level was evaluated by IHC and/or fluorescence in situ hybridization (FISH). RESULTS: In the primary lesions, 43.9% were ER positive; 46.7% were PR positive; 34.6% were HER-2 positive. In corresponding lymphatic metastatic lesions, the HER-2 status was concordant in 90 patients; 9 patients were diagnosed positive in metastatic lesion while negative in primary lesion; 8 patients were negative in metastatic lesion while positive in primary site (agreement, 84.1%; kappa=0.647). A change in ER status was observed in 24 cases: 17 cases positive in metastatic site while negative in primary site; 7 cases negative in metastatic site while positive in primary site (agreement, 77.6%; kappa=0.534). PR status discordance between the primary lesion and the metastatic regional lymph nodes was reported in 19 cases (agreement, 82.2%; kappa=0.640). CONCLUSIONS: This study revealed that there was only a moderate concordance of ER, PR and HER-2 status between primary tumors and metastatic lymph nodes. These results indicate that it was inappropriate to predict the status of ER, PR and HER-2 in metastatic lymph nodes based on the results of evaluation of that in primary lesions. PMID- 26899765 TI - Left ventricular non-compaction cardiomyopathy in children listed for heart transplant: Analysis from the Pediatric Heart Transplant Study Group. PMID- 26899766 TI - Virtual implantation of the 50cc SynCardia total artificial heart. PMID- 26899764 TI - Vascular inflammation and abnormal aortic histomorphometry in patients after pulsatile- and continuous-flow left ventricular assist device placement. AB - BACKGROUND: Left ventricular assist devices are increasingly being used in patients with advanced heart failure as both destination therapy and bridge to transplant. We aimed to identify histomorphometric, structural and inflammatory changes after pulsatile- and continuous-flow left ventricular assist device placement. METHODS: Clinical and echocardiographic data were collected from medical records. Aortic wall diameter, cellularity and inflammation were assessed by immunohistochemistry on aortic tissue collected at left ventricular assist device placement and at explantation during heart transplantation. Expression of adhesion molecules was quantified by Western blot. RESULTS: Decellularization of the aortic tunica media was observed in patients receiving continuous-flow support. Both device types showed an increased inflammatory response after left ventricular assist device placement with variable T-cell and macrophage accumulations and increased expression of vascular E-selectin, ICAM and VCAM in the aortic wall. CONCLUSIONS: Left ventricular assist device implantation is associated with distinct vascular derangements with development of vascular inflammation. These changes are pronounced in patients on continuous-flow left ventricular assist and associated with aortic media decellularization. The present findings help to explain the progressive aortic root dilation and vascular dysfunction in patients after continuous-flow device placement. PMID- 26899767 TI - Advanced heart failure secondary to muscular dystrophy: Clinical outcomes after left ventricular assist device implantation. PMID- 26899769 TI - The role of lung transplantation in excessive dynamic collapse. PMID- 26899768 TI - Genetic basis of familial dilated cardiomyopathy patients undergoing heart transplantation. AB - BACKGROUND: Dilated cardiomyopathy (DCM) is the most frequent cause of heart transplantation (HTx). The genetic basis of DCM among patients undergoing HTx has been poorly characterized. We sought to determine the genetic basis of familial DCM HTx and to establish the yield of modern next generation sequencing (NGS) technologies in this setting. METHODS: Fifty-two heart-transplanted patients due to familial DCM underwent NGS genetic evaluation with a panel of 126 genes related to cardiac conditions (59 associated with DCM). Genetic variants were initially classified as pathogenic mutations or as variants of uncertain significance (VUS). Final pathogenicity status was determined by familial cosegregation studies. RESULTS: Initially, 24 pathogenic mutations were found in 21 patients (40%); 25 patients (48%) carried 19 VUS and 6 (12%) did not show any genetic variant. Familial evaluation of 220 relatives from 36 of the 46 families with genetic variants confirmed pathogenicity in 14 patients and allowed reclassification of VUS as pathogenic in 17 patients, and as non-pathogenic in 3 cases. At the end of the study, the DCM-causing mutation was identified in 38 patients (73%) and 5 patients (10%) harbored only VUS. No genetic variants were identified in 9 cases (17%). CONCLUSIONS: The genetic spectrum of familial DCM patients undergoing HTx is heterogeneous and involves multiple genes. NGS technology plus detailed familial studies allow identification of causative mutations in the vast majority of familial DCM cases. Detailed familial studies remain critical to determine the pathogenicity of underlying genetic defects in a substantial number of cases. PMID- 26899770 TI - Improved heart function from older donors using pharmacologic conditioning strategies. AB - BACKGROUND: Hearts from older donors are increasingly being referred for transplantation. However, these hearts are more susceptible to ischemia reperfusion injury (IRI), reflected in higher rates of primary graft dysfunction. We assessed a strategy of pharmacologic conditioning, supplementing Celsior (Genzyme, Naarden, The Netherlands) preservation solution with glyceryl trinitrate (GTN; Hospira Australia Pty, Ltd, Mulgrave, VIC, Australia), erythropoietin (EPO; Eprex; Janssen-Cilag, North Ryde, NSW, Australia), and zoniporide (ZON; Pfizer, Inc., Groton, CT), to protect older hearts against IRI and improve graft function. METHODS: Wistar rats, aged 3, 12, and 18 months old, were used to represent adolescent, 30-year-old, and 45-year-old human donors, respectively. Animals were subjected to brain death (BD) and hearts stored for 6 hours at 2 degrees to 3 degrees C in Celsior or Celsior supplemented with GTN+EPO+ZON. Cardiac function and lactate dehydrogenase before and after storage were assessed during ex vivo perfusion. Western blots and histopathology were also analyzed. RESULTS: After BD, 18-month hearts demonstrated impaired aortic flow, coronary flow, and cardiac output compared with 3-month hearts (p < 0.001 to p < 0.0001). After storage in Celsior, the recovery of aortic flow, coronary flow, and cardiac output in 18-month BD hearts was further impaired (p < 0.01 vs 3-month hearts). Percentage functional recovery of 18-month BD hearts stored in Celsior supplemented with GTN+EPO+ZON was equivalent to that of 3-month hearts and significantly improved compared with 18-month hearts stored in Celsior alone (p < 0.01 to p < 0.001), with reduced lactate dehydrogenase release (p < 0.01) and myocardial edema (p < 0.05) and elevated phosphorylated extracellular signal related kinase 1/2 (p < 0.05) and phosphorylated Akt (p < 0.01). CONCLUSIONS: Older hearts are more susceptible to IRI induced by BD and prolonged hypothermic storage. Supplemented Celsior activates cell survival signaling in older hearts, reduces IRI, and enhances donor heart preservation. PMID- 26899771 TI - Successful therapy of pancreatitis after heart transplantation-A case series. PMID- 26899773 TI - Global public health today: connecting the dots. AB - BACKGROUND: Global public health today faces new challenges and is impacted by a range of actors from within and outside state boundaries. The diversity of the actors involved has created challenges and a complex environment that requires a new context-tailored global approach. The World Federation of Public Health Associations has embarked on a collaborative consultation with the World Health Organization to encourage a debate on how to adapt public health to its future role in global health. DESIGN: A qualitative study was undertaken. High-level stakeholders from leading universities, multilateral organizations, and other institutions worldwide participated in the study. Inductive content analyses were performed. RESULTS: Stakeholders underscored that global public health today should tackle the political, commercial, economic, social, and environmental determinants of health and social inequalities. A multisectoral and holistic approach should be guaranteed, engaging public health in broad dialogues and a concerted decision-making process. The connection between neoliberal ideology and public health reforms should be taken into account. The WHO must show leadership and play a supervising and technical role. More and better data are required across many programmatic areas of public health. Resources should be allocated in a sustainable and accountable way. Public health professionals need new skills that should be provided by a collaborative global education system. A common framework context-tailored to influence governments has been evaluated as useful. CONCLUSIONS: The study highlighted some of the main public health challenges currently under debate in the global arena, providing interesting ideas. A more inclusive integrated vision of global health in its complexity, shared and advocated for by all stakeholders involved in decision-making processes, is crucial. This vision represents the first step in innovating public health at the global level and should lead to a serious rethinking of education curricula to allow the next generation to engage within political contexts for restructuring global public health. PMID- 26899772 TI - New-onset diabetes after renal transplantation in a patient with a novel HNF1B mutation. AB - CAKUT are the most frequent causes of ESRD in children. Mutations in the gene encoding HNF1B, a transcription factor involved in organ development and maintenance, cause a multisystem disorder that includes CAKUT, diabetes, and liver dysfunction. Here, we describe the case of a patient with renal hypodysplasia who developed NODAT presenting with liver dysfunction. The NODAT was initially thought to be steroid and FK related. However, based on the patient's clinical features, including renal hypodysplasia and recurrent elevations of transaminase, screening for an HNF1B mutation was performed. Direct sequencing identified a novel splicing mutation of HNF1B, designated c.344 + 2T>C. Because CAKUT is the leading cause of ESRD in children and HNF1B mutations can cause both renal hypodysplasia and diabetes, HNF1B mutations may account for a portion of the cases of NODAT in pediatric patients who have undergone kidney transplantation. NODAT is a serious and major complication of solid organ transplantation and is associated with reduced graft survival. Therefore, for the appropriate management of kidney transplantation, screening for HNF1B mutations should be considered in pediatric patients with transplants caused by CAKUT who develop NODAT and show extra-renal symptoms. PMID- 26899774 TI - Implementation of the Integrated Management of Childhood Illnesses strategy: challenges and recommendations in Botswana. AB - BACKGROUND: Under-five mortality has been a major public health challenge from time immemorial. In response to this challenge, the World Health Organization and the United Nations Children's Fund developed the Integrated Management of Childhood Illnesses (IMCI) strategy and presented it to the whole world as a key approach to reduce child morbidity and mortality. Botswana started to implement the IMCI strategy in 1998. Reductions in the under-five mortality rate (U5MR) have been documented, although the reduction is not on par with the expected Millennium Development Goal 4 predictions. DESIGN: A quantitative study was done to identify the problems IMCI implementers face when tending children under 5 years in the Gaborone Health District of Botswana. The study population was made up of all the IMCI-trained and registered nurses, and systematic sampling was used to randomly select study participants. Questionnaires were used to collect data. RESULTS: The study findings indicated challenges related to low training coverage, health systems, and the unique features of the IMCI strategy. CONCLUSIONS: The comprehensive implementation of the IMCI strategy has the potential to significantly influence the U5MR in Botswana. PMID- 26899775 TI - Realizing omnidirectional light harvesting by employing hierarchical architecture for dye sensitized solar cells. AB - To improve the omnidirectional light-harvesting in dye-sensitized solar cells (DSSCs), here we present a dandelion-like structure composed of ZnO hemispherical shells and nanorods. Uniformly distributed hemispherical shells effectively suppress the reflection over the broadband region at incident angles up to 60 degrees , greatly improving the optical absorption of the DSSCs. In addition, modulating the length of the ZnO nanorods controls the omnidirectional characteristics of DSSCs. This phenomenon is attributed to the degree of periodicity of the ZnO dandelion-like structures. Cells with shorter rods exhibit a high degree of periodicity, thus the conversion efficiencies of the cells show specific angle-independent features. On the other hand, the cells with longer lengths reveal angle-dependent photovoltaic performance. Along with the simulation, the cells with dandelion-like ZnO structures can couple incident photons efficiently to achieve excellent broadband and omnidirectional light harvesting performances experimentally, and the DSSCs enhanced the conversion efficiency by 48% at large incident angles. All these findings not only provide further insight into the light-trapping mechanism in these complex three dimensional nanostructures but also offer efficient omnidirectional and broadband nanostructured photovoltaics for advanced applications. PMID- 26899777 TI - Skinfold creep under load of caliper. Linear visco- and poroelastic model simulations. AB - PURPOSE: This paper addresses the diagnostic idea proposed in [11] to measure the parameter called rate of creep of axillary fold of tissue using modified Harpenden skinfold caliper in order to distinguish normal and edematous tissue. Our simulations are intended to help understanding the creep phenomenon and creep rate parameter as a sensitive indicator of edema existence. The parametric analysis shows the tissue behavior under the external load as well as its sensitivity to changes of crucial hydro-mechanical tissue parameters, e.g., permeability or stiffness. METHODS: The linear viscoelastic and poroelastic models of normal (single phase) and oedematous tissue (twophase: swelled tissue with excess of interstitial fluid) implemented in COMSOL Multiphysics environment are used. Simulations are performed within the range of small strains for a simplified fold geometry, material characterization and boundary conditions. The predicted creep is the result of viscosity (viscoelastic model) or pore fluid displacement (poroelastic model) in tissue. RESULTS: The tissue deformations, interstitial fluid pressure as well as interstitial fluid velocity are discussed in parametric analysis with respect to elasticity modulus, relaxation time or permeability of tissue. The creep rate determined within the models of tissue is compared and referred to the diagnostic idea in [11]. CONCLUSIONS: The results obtained from the two linear models of subcutaneous tissue indicate that the form of creep curve and the creep rate are sensitive to material parameters which characterize the tissue. However, the adopted modelling assumptions point to a limited applicability of the creep rate as the discriminant of oedema. PMID- 26899776 TI - [Prevention of infections in adults and adolescents with systemic lupus erythematosus: Guidelines for the clinical practice based on the literature and expert opinion]. AB - PURPOSE: To develop French recommendations about the management of vaccinations, the screening of cervical cancer and the prevention of pneumocystis pneumonia in systemic lupus erythematosus (SLE). METHODS: Thirty-seven experts qualified in internal medicine, rheumatology, dermatology, nephrology and pediatrics have selected recommendations from a list of proposition based on available data from the literature. For each recommendation, the level of evidence and the level of agreement among the experts were specified. RESULTS: Inactivated vaccines do not cause significant harm in SLE patients. Experts recommend that lupus patient should receive vaccinations accordingly to the recommendations and the schedules for the general public. Pneumococcal vaccination is recommended for all SLE patients. Influenza vaccination is recommended for immunosuppressed SLE patients. Live attenuated vaccines should be avoided in immunosuppressed patients. Yet, recent works suggest that they can be considered in mildly immunosuppressed patients. Experts have recommended a cervical cytology every year for immunosuppressed patients. No consensus was obtained for the prevention of pneumocystis pneumonia. CONCLUSION: These recommendations can be expected to improve clinical practice uniformity and, in the longer term, to optimize the management of SLE patients. PMID- 26899779 TI - Immunomodulatory agents in mantle cell lymphoma. PMID- 26899780 TI - Exploratory Analysis on Overall Survival after Either Surgery or Stereotactic Radiotherapy for Lung Oligometastases from Colorectal Cancer. AB - AIMS: Lung metastasectomy and, more recently, stereotactic body radiotherapy (SBRT), are frequently proposed to stage IV oligometastatic colorectal cancer (CRC) patients. In the absence of a randomised comparison between the two treatments, we aimed to retrospectively explore the effect on overall survival and progression-free survival (PFS) in a comparative cohort study. MATERIALS AND METHODS: We included patients who consecutively underwent surgery (n = 142) or SBRT (n = 28) as first local therapy at the time of lung progression, between 2005 and 2012. Both overall survival and PFS functions according to treatment were calculated using the Kaplan-Meier method and compared using the Log-rank test. The effect of treatment on overall survival and PFS was estimated by Cox models using different adjustment methods. RESULTS: Patients receiving SBRT were older and were treated more recently, whereas the two cohorts were similar for most baseline prognostic factors. Overall survival at 1 and 2 years was 0.89 and 0.77 for SBRT and 0.96 and 0.82 for surgery (P = 0.134), respectively. Multivariable analyses did not highlight a clear treatment effect on overall survival (adjusted hazard ratioSBRT versus surgery = 1.71; 95% confidence interval 0.82-3.54; P = 0.149) and even smaller differences using the inverse probability treatment weighting method (hazard ratioSBRT versus surgery = 1.28, 95% confidence interval 0.58-2.82; P = 0.547). The results of PFS were unreliable because different follow-up protocols were applied in the two cohorts. CONCLUSION: With limitations consisting in the retrospective observational design and different sample sizes, the results of this explorative analysis indicate that overall survival probability after SBRT is similar to surgery for the first 2 years from treatment. This finding supports the need for high-quality trials comparing different treatment modalities for lung oligometastases from CRC. PMID- 26899778 TI - Lenalidomide versus investigator's choice in relapsed or refractory mantle cell lymphoma (MCL-002; SPRINT): a phase 2, randomised, multicentre trial. AB - BACKGROUND: Lenalidomide, an immunomodulatory drug with antineoplastic and antiproliferative effects, showed activity in many single-group studies in relapsed or refractory mantle cell lymphoma. The aim of this randomised study was to examine the efficacy and safety of lenalidomide versus best investigator's choice of single-agent therapy in relapsed or refractory mantle cell lymphoma. METHODS: The MCL-002 (SPRINT) study was a randomised, phase 2 study of patients with mantle cell lymphoma aged 18 years or older at 67 clinics and academic centres in 12 countries who relapsed one to three times, had Eastern Cooperative Oncology Group performance status of 0-2, at least one measurable lesion to be eligible, and who were ineligible for intensive chemotherpy or stem-cell transplantation. Using a centralised interactive voice response system, we randomly assigned (2:1) patients in a permuted block size of six to receive lenalidomide (25 mg orally on days 1-21 every 28 days) until progressive disease or intolerability, or single-agent investigator's choice of either rituximab, gemcitabine, fludarabine, chlorambucil, or cytarabine. Randomisation was stratified by time from diagnosis, time from last anti-lymphoma therapy, and previous stem-cell transplantation. Individual treatment assignment between lenalidomide and investigator's choice was open label, but investigators had to register their choice of comparator drug before randomly assigning a patient. Patients who progressed on investigator's choice could cross over to lenalidomide treatment. We present the prespecified primary analysis results in the intention to-treat population for the primary endpoint of progression-free survival, defined as the time from randomisation to progressive disease or death, whichever occurred first. Patient enrolment is complete, although treatment and collection of additional time-to-event data are ongoing. This study is registered with ClinicalTrials.gov, number NCT00875667. FINDINGS: Between April 30, 2009, and March 7, 2013, we enrolled 254 patients in the intention-to-treat population (170 [67%] were randomly assigned to receive lenalidomide, 84 [33%] to receive investigator's choice monotherapy). Patients had a median age of 68.5 years and received a median of two previous regimens. With a median follow-up of 15.9 months (IQR 7.6-31.7), lenalidomide significantly improved progression-free survival compared with investigator's choice (median 8.7 months [95% CI 5.5-12.1] vs 5.2 months [95% CI 3.7-6.9]) with a hazard ratio of 0.61 (95% CI 0.44-0.84; p=0.004). In the 167 patients in the lenalidomide group and 83 patients in the investigator's choice group who received at least one dose of treatment the most common grade 3-4 adverse events included neutropenia (73 [44%] of 167 vs 28 [34%] of 83) without increased risk of infection, thrombocytopenia (30 [18%] vs 23 [28%]), leucopenia (13 [8%] vs nine [11%]), and anaemia (14 [8%] vs six [7%]). INTERPRETATION: Patients with relapsed or refractory mantle cell lymphoma ineligible for intensive chemotherapy or stem-cell transplantation have longer progression-free survival, with a manageable safety profile when treated with lenalidomide compared with monotherapy investigator's choice options. FUNDING: Celgene Corporation. PMID- 26899782 TI - The effect of spatial resolution on decoding accuracy in fMRI multivariate pattern analysis. AB - Multivariate pattern analysis (MVPA) in fMRI has been used to extract information from distributed cortical activation patterns, which may go undetected in conventional univariate analysis. However, little is known about the physical and physiological underpinnings of MVPA in fMRI as well as about the effect of spatial smoothing on its performance. Several studies have addressed these issues, but their investigation was limited to the visual cortex at 3T with conflicting results. Here, we used ultra-high field (7T) fMRI to investigate the effect of spatial resolution and smoothing on decoding of speech content (vowels) and speaker identity from auditory cortical responses. To that end, we acquired high-resolution (1.1mm isotropic) fMRI data and additionally reconstructed them at 2.2 and 3.3mm in-plane spatial resolutions from the original k-space data. Furthermore, the data at each resolution were spatially smoothed with different 3D Gaussian kernel sizes (i.e. no smoothing or 1.1, 2.2, 3.3, 4.4, or 8.8mm kernels). For all spatial resolutions and smoothing kernels, we demonstrate the feasibility of decoding speech content (vowel) and speaker identity at 7T using support vector machine (SVM) MVPA. In addition, we found that high spatial frequencies are informative for vowel decoding and that the relative contribution of high and low spatial frequencies is different across the two decoding tasks. Moderate smoothing (up to 2.2mm) improved the accuracies for both decoding of vowels and speakers, possibly due to reduction of noise (e.g. residual motion artifacts or instrument noise) while still preserving information at high spatial frequency. In summary, our results show that - even with the same stimuli and within the same brain areas - the optimal spatial resolution for MVPA in fMRI depends on the specific decoding task of interest. PMID- 26899781 TI - Transcription reactivation during the first meiotic prophase in bugs is not dependent on synapsis. AB - During meiosis, transcription is precisely regulated in relation to the process of chromosome synapsis. In mammals, transcription is very low until the completion of synapsis in early pachytene, and then reactivates during mid pachytene, up to the end of diplotene. Moreover, chromosomes or chromosomal regions that do not achieve synapsis undergo a specific process of inactivation called meiotic silencing of unpaired chromatin (MSUC). Sex chromosomes, which are mostly unsynapsed, present a special case of inactivation named meiotic sex chromosome inactivation (MSCI). Although processes that are similar to MSUC/MSCI have been described in other species like Sordaria and Caenorhabditis elegans, very few studies have been developed in insects. We present a study on the relationships between synapsis and transcription in two hemipteran species (Graphosoma italicum and Carpocoris fuscispinus) that possess holocentric chromosomes but develop different synaptic patterns. We have found that transcription, revealed by the presence of RNA polymerase II, is very low at the beginning of meiosis, but robustly increases during zygotene, long before the completion of synapsis, excepting in the sex chromosomes. In fact, we show that histone H3 methylation at lysine 9 (H3K9me3) may be present in the sex chromosomes at leptotene, thus acting as a likely epigenetic mark for this inactive state. Our results suggest that the meiotic transcription in these two species is differently regulated from that of mammals and, therefore, offer new opportunities to understand the relationship between synapsis and transcription and the mechanisms that govern MSUC/MSCI processes. PMID- 26899783 TI - The effect of aging on fronto-striatal reactive and proactive inhibitory control. AB - Inhibitory control, like most cognitive processes, is subject to an age-related decline. The effect of age on neurofunctional inhibition processing remains uncertain, with age-related increases as well as decreases in activation being reported. This is possibly because reactive (i.e., outright stopping) and proactive inhibition (i.e., anticipation of stopping) have not been evaluated separately. Here, we investigate the effects of aging on reactive as well as proactive inhibition, using functional MRI in 73 healthy subjects aged 30 70years. We found reactive inhibition to slow down with advancing age, which was paralleled by increased activation in the motor cortex. Behaviorally, older adults did not exercise increased proactive inhibition strategies compared to younger adults. However, the pattern of activation in the right inferior frontal gyrus (rIFG) showed a clear age-effect on proactive inhibition: rather than flexibly engaging the rIFG in response to varying stop-signal probabilities, older subjects showed an overall hyperactivation. Whole-brain analyses revealed similar hyperactivations in various other frontal and parietal brain regions. These results are in line with the neural compensation hypothesis of aging: processing becomes less flexible and efficient with advancing age, which is compensated for by overall enhanced activation. Moreover, by disentangling reactive and proactive inhibition, we can show for the first time that the age related increase in activation during inhibition that is reported generally by prior studies may be the result of compensation for reduced neural flexibility related to proactive control strategies. PMID- 26899784 TI - Financial literacy is associated with white matter integrity in old age. AB - Financial literacy, the ability to understand, access, and utilize information in ways that contribute to optimal financial outcomes, is important for independence and wellbeing in old age. We previously reported that financial literacy is associated with greater functional connectivity between brain regions in old age. Here, we tested the hypothesis that higher financial literacy would be associated with greater white matter integrity in old age. Participants included 346 persons without dementia (mean age=81.36, mean education=15.39, male/female=79/267, mean MMSE=28.52) from the Rush Memory and Aging Project. Financial literacy was assessed using a series of questions imbedded as part of an ongoing decision making study. White matter integrity was assessed with diffusion anisotropy measured with diffusion tensor magnetic resonance imaging (DTI). We tested the hypothesis that higher financial literacy is associated with higher diffusion anisotropy in white matter, adjusting for the effects of age, education, sex, and white matter hyperintense lesions. We then repeated the analysis also adjusting for cognitive function. Analyses revealed regions with significant positive associations between financial literacy and diffusion anisotropy, and many remained significant after accounting for cognitive function. White matter tracts connecting right hemisphere temporal-parietal brain regions were particularly implicated. Greater financial literacy is associated with higher diffusion anisotropy in white matter of nondemented older adults after adjusting for important covariates. These results suggest that financial literacy is positively associated with white matter integrity in old age. PMID- 26899786 TI - Voluntary control of anterior insula and its functional connections is feedback independent and increases pain empathy. AB - Real-time functional magnetic resonance imaging (rtfMRI)-assisted neurofeedback (NF) training allows subjects to acquire volitional control over regional brain activity. Emerging evidence suggests its potential clinical utility as an effective non-invasive treatment approach in mental disorders. The therapeutic potential of rtfMRI-NF training depends critically upon whether: (1) acquired self-regulation produces functionally relevant changes at behavioral and brain network levels and (2) training effects can be maintained in the absence of feedback. To address these key questions, the present study combined rtfMRI-NF training for acquiring volitional anterior insula (AI) regulation with a sham controlled between-subject design. The functional relevance of acquired AI control was assessed using both behavioral (pain empathy) and neural (activity, functional connectivity) indices. Maintenance of training effects in the absence of feedback was assessed two days later. During successful acquisition of volitional AI up-regulation subjects exhibited stronger empathic responses, increased AI-prefrontal coupling in circuits involved in learning and emotion regulation and increased resting state connectivity within AI-centered empathy networks. At follow-up both self-regulation and increased connectivity in empathy networks were fully maintained, although without further increases in empathy ratings. Overall these findings support the potential clinical application of rtfMRI-NF for inducing functionally relevant and lasting changes in emotional brain circuitry. PMID- 26899785 TI - A ventral salience network in the macaque brain. AB - Successful navigation of the environment requires attending and responding efficiently to objects and conspecifics with the potential to benefit or harm (i.e., that have value). In humans, this function is subserved by a distributed large-scale neural network called the "salience network". We have recently demonstrated that there are two anatomically and functionally dissociable salience networks anchored in the dorsal and ventral portions of the human anterior insula (Touroutoglou et al., 2012). In this paper, we test the hypothesis that these two subnetworks exist in rhesus macaques (Macaca mulatta). We provide evidence that a homologous ventral salience network exists in macaques, but that the connectivity of the dorsal anterior insula in macaques is not sufficiently developed as a dorsal salience network. The evolutionary implications of these finding are considered. PMID- 26899787 TI - Magnetic susceptibility of brain iron is associated with childhood spatial IQ. AB - Iron is an essential micronutrient for healthy brain function and development. Because of the importance of iron in the brain, iron deficiency results in widespread and lasting effects on behavior and cognition. We measured iron in the basal ganglia of young children using a novel MRI method, quantitative susceptibility mapping, and examined the association of brain iron with age and cognitive performance. Participants were a community sample of 39 young children recruited from pediatric primary care who were participating in a 5-year longitudinal study of child brain development and anxiety disorders. The children were ages 7 to 11years old (mean age: 9.5years old) at the time of the quantitative susceptibility mapping scan. The differential abilities scale was administered when the children were 6years old to provide a measure of general intelligence and verbal (receptive and expressive), non-verbal, and spatial performance. Magnetic susceptibility values, which are linearly related to iron concentration in iron-rich areas, were extracted from regions of interest within iron-rich deep gray matter nuclei from the basal ganglia, including the caudate, putamen, substantia nigra, globus pallidus, and thalamus. Controlling for scan age, there was a significant positive association between iron in the basal ganglia and spatial IQ, with this effect being driven by iron in the right caudate We also replicated previous findings of a significant positive association between iron in the bilateral basal ganglia and age. Our finding of a positive association between spatial IQ and mean iron in the basal ganglia, and in the caudate specifically, suggests that iron content in specific regions of the iron-rich deep nuclei of the basal ganglia influences spatial intelligence. This provides a potential neurobiological mechanism linking deficits in spatial abilities reported in children who were severely iron deficient as infants to decreased iron within the caudate. PMID- 26899789 TI - Particle alignment reliability in single particle electron cryomicroscopy: a general approach. AB - Electron Microscopy is reaching new capabilities thanks to the combined effect of new technologies and new image processing methods. However, the reconstruction process is still complex, requiring many steps and elaborated optimization procedures. Therefore, the possibility to reach a wrong structure exists, justifying the need of robust statistical tests. In this work, we present a conceptually simple alignment test, which does not require tilt-pair images, to evaluate the alignment consistency between a set of projection images with respect to a given 3D density map. We test the approach on a number of problems in 3DEM, especially the ranking and evaluation of initial 3D volumes and high resolution 3D maps, where we show its usefulness in providing an objective evaluation for maps that have recently been subject to a strong controversy in the field. Additionally, this alignment statistical test can be linked to the early stages of structure solving of new complexes, streamlining the whole process. PMID- 26899791 TI - New developments in porphyrin-like macrocyclic chemistry: a novel family of dibenzotetraaza[14]annulene-based cofacial dimers. AB - The first known homoleptic cofacial dimers, based on covalently linked dibenzotetraaza[14]annulenes, were synthesized in reasonable 35-40% yields, without recourse to high-dilution techniques. Dinuclear zinc(ii) dimer showed strong binding affinity toward DABCO. Site-selective monometallation of the dimer, triggered by the linkers' structure, was observed, allowing access to heterobimetallic co-receptors. PMID- 26899788 TI - Direct neural current imaging in an intact cerebellum with magnetic resonance imaging. AB - The ability to detect neuronal currents with high spatiotemporal resolution using magnetic resonance imaging (MRI) is important for studying human brain function in both health and disease. While significant progress has been made, we still lack evidence showing that it is possible to measure an MR signal time-locked to neuronal currents with a temporal waveform matching concurrently recorded local field potentials (LFPs). Also lacking is evidence that such MR data can be used to image current distribution in active tissue. Since these two results are lacking even in vitro, we obtained these data in an intact isolated whole cerebellum of turtle during slow neuronal activity mediated by metabotropic glutamate receptors using a gradient-echo EPI sequence (TR=100ms) at 4.7T. Our results show that it is possible (1) to reliably detect an MR phase shift time course matching that of the concurrently measured LFP evoked by stimulation of a cerebellar peduncle, (2) to detect the signal in single voxels of 0.1mm(3), (3) to determine the spatial phase map matching the magnetic field distribution predicted by the LFP map, (4) to estimate the distribution of neuronal current in the active tissue from a group-average phase map, and (5) to provide a quantitatively accurate theoretical account of the measured phase shifts. The peak values of the detected MR phase shifts were 0.27-0.37 degrees , corresponding to local magnetic field changes of 0.67-0.93nT (for TE=26ms). Our work provides an empirical basis for future extensions to in vivo imaging of neuronal currents. PMID- 26899790 TI - Immunological and biochemical characterizations of coxsackievirus A6 and A10 viral particles. AB - Childhood exanthema caused by different serotypes of coxsackievirus (CV-A) and enterovirus A71 (EV-A71) has become a serious global health problem; it is commonly known as hand, foot, and mouth disease (HFMD). Current EV-A71 vaccine clinical trials have demonstrated that human antibody responses generated by EV A71 vaccinations do not cross-neutralize coxsackievirus A16 (CV-A16). An effective multivalent HFMD vaccine is urgently needed. From molecular epidemiological studies in Southeast Asia, CV-A6 and CV-A10 are commonly found in HFMD outbreaks. In this study, CV-A6 and CV-A10 were individually cultured in rhabdomyosarcoma (RD) cells grown in medium containing serum, harvested and concentrated. In viral downstream purification, two viral fractions were separated by sucrose gradient zonal ultracentrifugation and detected using a SDS PAGE analysis and a virus infectivity assay. These two viral fractions were formalin-inactivated, and only the infectious particle fraction was found to be capable of inducing CV-A serotype-specific neutralizing antibody responses in animal immunogenicity studies. These mouse and rabbit antisera also failed to cross-neutralize EV-A71 and CV-A16 infections. Only a combination of formalin inactivated EV-A71, CV-A6, CV-A10 and CV-A16 multivalent vaccine candidates elicited cross-neutralizing antibody responses in both mouse and rabbit immunogenicity studies. The current results certainly provide important information for multivalent HFMD vaccine development. PMID- 26899792 TI - Computational prediction of optimal metal ions to induce coordinated polymerization of muscle-like [c2]daisy chains. AB - Recently, a muscle-like organometallic polymer has been successfully synthesized using Fe(2+) as a linker atom. The polymer exhibits acid-base controllable muscle like expansion and contraction on the micrometer scale. Further development could be facilitated by revealing the polymerization mechanism and by searching for optimal linker atoms. In this work, we have examined possible equilibrium and intermediate polymer structures, which consist of [c2]daisy chains linked by divalent transition metal ions (Sc(2+), Ti(2+), Fe(2+), Co(2+), Ni(2+) or Zn(2+)) with various hexa-coordination arrangements, based on calculations using density functional theory. We find that the metal linkers in polymers are weaker in acid than in base due to excess positive charges on the polymer, leading to their thermodynamical instability or even decomposition. This can explain the experimental difficulty in improving the degree of polymerization for metal linked polymers. We also find that the polymers with either Fe(2+) or Co(2+) are the most favorable, with the latter extending 1.4% longer than with the former. Since Fe(2+) has been confirmed experimentally to be a successful linker, Co(2+) would function equally well and thus could be used as an alternative choice for polymerization. PMID- 26899793 TI - Eco-evolutionary feedback promotes Red Queen dynamics and selects for sex in predator populations. AB - Although numerous hypotheses exist to explain the overwhelming presence of sexual reproduction across the tree of life, we still cannot explain its prevalence when considering all inherent costs involved. The Red Queen hypothesis states that sex is maintained because it can create novel genotypes with a selective advantage. This occurs when the interactions between species induce frequent environmental change. Here, we investigate whether coevolution and eco-evolutionary feedback dynamics in a predator-prey system allows for indirect selection and maintenance of sexual reproduction in the predator. Combining models and chemostat experiments of a rotifer-algae system we show a continuous feedback between population and trait change along with recurrent shifts from selection by predation and competition for a limited resource. We found that a high propensity for sex was indirectly selected and was maintained in rotifer populations within environments containing these eco-evolutionary dynamics; whereas within environments under constant conditions, predators evolved rapidly to lower levels of sex. Thus, our results indicate that the influence of eco-evolutionary feedback dynamics on the overall evolutionary change has been underestimated. PMID- 26899794 TI - Quantitative CT indexes are significantly associated with exercise oxygen desaturation in interstitial lung disease related to systemic sclerosis. AB - INTRODUCTION: Interstitial Lung Disease (ILD) is the first cause of death related to Systemic Sclerosis (SSc). The ILD severity can be assessed with clinical, functional and radiological outcome. Nevertheless none of them is completely validated in clinical practice. Recently a new radiological evaluation based on Quantitative Computed Tomography Indexes (QCTI) was proposed on the basis of voxel-wise quantitative analysis of chest CT. OBJECTIVES: The main aim of this study is to verify if QCTI can identify SSc patients with significant oxygen desaturation during the 6 min walking test. The discrimination performance of QCTI and the other clinical, functional and radiological outcomes was also investigated. METHODS: Sixty three SSc patients were enrolled and underwent clinical, functional and radiological assessment. Inspiratory chest CT of each patient was evaluated with both a visual score and a dedicated software for segmentation of the lung in order to obtained QCTI. RESULTS: Patients with or without severe oxygen desaturation showed different QCTI, CT visual score and functional outcomes (P < 0.05). In particular, QCTI and functional outcomes showed almost the same discriminating ability. CONCLUSION: QCTI detect SSc patients with a severe oxygen desaturation after exercise as well as functional and other radiological outcomes. It is remarkable that QCTI are the only outcome without intra- or inter-reader variability because they are obtained with an algorithm. These findings bring out the QCTI as a concrete tool in SSc-ILD assessment. PMID- 26899796 TI - Single level anterior cervical discectomy and fusion for cervical disc herniation in a professional soccer player. AB - A 29-year old midfielder playing professional soccer complains of neck and right shoulder pain without apparent cause. A cervical MR shows disc herniation between C4 and C5 compressing 5th nerve root. The patient undergoes surgical discectomy plus interbody fusion with autologous bone and plate fixation with unicortical screws. No surgical complication is observed and after four weeks of rest, the patient begins a specific rehabilitation program including Tecar Therapy sessions and manual passive physical therapy for six weeks. Two times a week he attends hydrokinesis sessions. After eight weeks the athlete can restart working directly on soccer field and after less than four months he is back on an official competition. PMID- 26899797 TI - Walking at non-constant speeds: mechanical work, pendular transduction, and energy congruity. AB - Although almost half of all walking bouts in urban environments consist of less than 12 consecutive steps and several day-to-day gait activities contain transient gait responses, in most studies gait analysis is performed at steady state. This study aimed to analyze external (Wext ) and internal mechanical work (Wint ), pendulum-like mechanics, and elastic energy usage during constant and non-constant speeds. The mechanical work, pendular transduction, and energy congruity (an estimate of storage and release of elastic energy) during walking were computed using two force platforms. We found that during accelerating gait (+NCS) energy recovery is maintained, besides extra W+ext , for decelerating gait (-NCS) poor energy recovery was counterbalanced by W-ext and C% predominance. We report an increase in elastic energy usage with speed (4-11%). Both W-ext and %C suggests that elastic energy usage is higher at faster speeds and related to -NCS (~20% of elastic energy usage). This study was the first to show evidences of elastic energy usage during constant and non-constant speeds. PMID- 26899795 TI - HMGB1 Facilitated Macrophage Reprogramming towards a Proinflammatory M1-like Phenotype in Experimental Autoimmune Myocarditis Development. AB - Macrophages can be reprogramming, such as the classical activated macrophage, M1 or alternative activated macrophages, M2 phenotype following the milieu danger signals, especially inflammatory factors. Macrophage reprogramming is now considered as a key determinant of disease development and/or regression. Experimental autoimmune myocarditis (EAM) is characterized by monocytes/macrophage infiltration, Th17 cells activation and inflammatory factors producing such as high mobility group box 1 (HMGB1). Whether infiltrated macrophages could be reprogramming in EAM? HMGB1 was associated with macrophage reprogramming? Our results clearly demonstrated that infiltrated macrophage was reprogrammed towards a proinflammatory M1-like phenotype and cardiac protection by monocytes/macrophages depletion or HMGB1 blockade in EAM; in vitro, HMGB1 facilitated macrophage reprogramming towards M1-like phenotype dependent on TLR4 PI3Kgamma-Erk1/2 pathway; furthermore, the reprogramming M1-like macrophage promoted Th17 expansion. Therefore, we speculated that HMGB1 contributed EAM development via facilitating macrophage reprogramming towards M1-like phenotype except for directly modulating Th17 cells expansion. PMID- 26899798 TI - Primary caregivers of in-home oxygen-dependent children: predictors of stress based on characteristics, needs and social support. AB - AIM: To identify the predictors of primary caregivers' stress in caring for in home oxygen-dependent children by examining the association between their levels of stress, caregiver needs and social support. BACKGROUND: Increasing numbers of primary caregivers of oxygen-dependent children experience caregiving stress that warrants investigation. DESIGN: The study used a cross-sectional design with three psychometric scales - Modified-Parenting Stress Index, Caregiver Needs Scale and Social Support Index. METHODS: The data collected during 2010-2011 were from participants who were responsible for their child's care that included oxygen therapy for ?6 hours/day; the children's ages ranged from 3 months-16 years. Descriptive statistics and multivariable linear regression were used. RESULTS: A total of 104 participants (M = 34, F = 70) were recruited, with an average age of 39.7 years. The average age of the oxygen-dependent children was 6.68 years and their daily use of oxygen averaged 11.39 hours. The caregivers' overall levels of stress were scored as high and information needs were scored as the highest. The most available support from family and friends was emotional support. Informational support was mostly received from health professionals, but both instrumental and emotional support were important. Levels of stress and caregiver needs were significantly correlated. Multivariable linear regression analyses identified three risk factors predicting stress, namely, the caregiver's poor health status, the child's male gender and the caregiver's greater financial need. CONCLUSION: To support these caregivers, health professionals can maintain their health status and provide instrumental, emotional, informational and financial support. PMID- 26899799 TI - LRRK2 pathobiology in Parkinson's disease - virtual inclusion. AB - A common cause of Parkinson disease are missense mutations in the leucine-rich repeat kinase 2 (LRRK2) catalytic Roc-COR domain, leading to a decrease in GTPase activity; and its kinase domain, leading to an increase in kinase activity and subsequent LRRK2 toxicity. Targeting LRRK2 with selective, brain-permeable kinase inhibitors is a promising approach to reduce toxicity, and thus is a major goal of clinical development. Understanding the specific signaling cascades triggered by LRRK2 mutations will be key to this aim. This article is part of a special issue on Parkinson disease. PMID- 26899800 TI - Revision Surgery of Deep Brain Stimulation Leads. AB - INTRODUCTION: Deep brain stimulation (DBS) is widely used for various movement disorders. DBS lead revisions are becoming more common as the indications and number of cases increases. METHODS: Patients undergoing DBS lead revisions at a single institution were retrospectively analyzed based on diagnosis, reason for revision, where the lead was relocated, and surgical technique. RESULTS: We reviewed 497 consecutive DBS lead placements and found that there was need for 25 DBS lead revisions with at least six months of follow-up. Loss of efficacy and development of adverse effects over time were the most common reasons for lead revision across all diagnosis. Lead malfunction was the least common. Ten patients requiring 19 DBS lead revisions that underwent their original surgery at another institution were also analyzed. Surgical technique dictated replacing with a new lead while maintaining brain position and tract with the old lead until final placement. Methods to seal exposed wire were developed. CONCLUSION: Surgical technique, as well as variable options are important in lead revision and can be dictated based on reason for revision. Over time patients who have had adequate relief with DBS placement may experience loss of efficacy and development of adverse effects requiring revision of the DBS lead to maintain its effects. PMID- 26899801 TI - John Henryism Active Coping as a Cultural Correlate of Substance Abuse Treatment Participation Among African American Women. AB - The rates of illicit drug use among African American women are increasing, yet African American women are least likely to participate in treatment for substance use disorders when compared to women of other racial groups. The current study examined family history of substance use, perceived family support, and John Henryism Active Coping (JHAC) as correlates to seeking treatment for substance abuse. The underlying theoretical frame of JHAC (James et al., 1983) suggests that despite limited resources and psychosocial stressors, African Americans believe that hard work and self-determination are necessary to cope with adversities. The current study is a secondary data analyses of 206 drug-using African American women (N=104 urban community women with no criminal justice involvement and N=102 women living in the community on supervised probation) from urban cities in a southern state. It was expected that African American women with a family history of substance abuse, higher levels of perceived family support, and more active coping skills would be more likely to have participated in substance abuse treatment. Step-wise logistic regression results reveal that women on probation, had children, and had a family history of substance abuse were significantly more likely to report participating in substance abuse treatment. Perceived family support and active coping were significant negative correlates of participating in treatment. Implication of results suggests coping with psychosocial stressors using a self-determined and persistent coping strategy may be problematic for drug-using women with limited resources. PMID- 26899802 TI - Estimating demand for primary care-based treatment for substance and alcohol use disorders. AB - BACKGROUND AND AIMS: While there is broad recognition of the high societal costs of substance use disorders (SUD), treatment rates are low. We examined whether, in the United States, participants with substance or alcohol use disorder would report a greater willingness to enter SUD treatment located in a primary care setting (primary care) or more commonly found specialty care setting in the United States (usual care). DESIGN: Randomized survey-embedded experiment. SETTING: US web-based research panel in which participants were randomized to read one-paragraph vignettes describing treatment in usual care (specialty drug or alcohol treatment center), primary care or collaborative care within a primary care setting. PARTICIPANTS: A total of 42 451 panelists aged 18+ were screened for substance or alcohol use disorder using validated diagnostic criteria. Participants included 344 with a substance use disorder and 634 with an alcohol use disorder not in treatment with no prior treatment history. MEASURES: Willingness to enter treatment across vignettes by condition. FINDINGS: Among participants with a substance use disorder, 24.6% of those randomized to usual care reported being willing to enter drug treatment compared with 37.2% for primary care [12.6 percentage point difference; 95% confidence interval (CI) = 0.8, 24.4) and 34.0% for collaborative care (9.4 percentage point difference; 95% CI = -2.0, 20.8). Among participants with an alcohol use disorder, 17.6% of those randomized to usual care reported being willing to enter alcohol treatment compared with 20.3% for primary care (2.6 percentage point difference; 95% CI = 4.9, 10.1) and 20.8% for collaborative care (3.1 percentage point difference; 95% CI = -4.3, 10.6). The most common reason for not being willing to enter drug (63%) and alcohol (78%) treatment was the belief that treatment was not needed. CONCLUSIONS: In the United States, people diagnosed with substance or alcohol use disorders appear to be more willing to enter treatment in a primary care setting than in a specialty drug treatment center. Expanding availability of primary care based substance use disorder treatment could increase treatment rates in the United States. PMID- 26899804 TI - Some chemical speculation on the biosynthesis of corallidictyals A-D. AB - The efficient conversion of siphonodictyal B into the spirocyclic natural products corallidictyals A-D has been achieved via oxidative and acid catalyzed cyclizations. The oxidative cyclization of siphonodictyal B occured spontaneously under aerobic oxidation conditions, which suggests that corallidictyals A and B are possibly artefacts of the isolation process. The mechanism of the oxidative cyclization of siphonodictyal B could be described as either an anionic 5-endo trig cyclization (which is formally disfavoured by Baldwin's rules), or as an electrocyclic reaction, of an ortho-quinone intermediate. PMID- 26899803 TI - Ocean acidification increases copper toxicity differentially in two key marine invertebrates with distinct acid-base responses. AB - Ocean acidification (OA) is expected to indirectly impact biota living in contaminated coastal environments by altering the bioavailability and potentially toxicity of many pH-sensitive metals. Here, we show that OA (pH 7.71; pCO2 1480 MUatm) significantly increases the toxicity responses to a global coastal contaminant (copper ~0.1 MUM) in two keystone benthic species; mussels (Mytilus edulis) and purple sea urchins (Paracentrotus lividus). Mussels showed an extracellular acidosis in response to OA and copper individually which was enhanced during combined exposure. In contrast, urchins maintained extracellular fluid pH under OA by accumulating bicarbonate but exhibited a slight alkalosis in response to copper either alone or with OA. Importantly, copper-induced damage to DNA and lipids was significantly greater under OA compared to control conditions (pH 8.14; pCO2 470 MUatm) for both species. However, this increase in DNA-damage was four times lower in urchins than mussels, suggesting that internal acid-base regulation in urchins may substantially moderate the magnitude of this OA-induced copper toxicity effect. Thus, changes in metal toxicity under OA may not purely be driven by metal speciation in seawater and may be far more diverse than either single-stressor or single-species studies indicate. This has important implications for future environmental management strategies. PMID- 26899805 TI - In situ chemical behaviour of methylisothiazolinone (MI) and methylchloroisothiazolinone (MCI) in reconstructed human epidermis: a new approach to the cross-reactivity issue. AB - BACKGROUND: Methylisothiazolinone (MI) [with methylchloroisothiazolinone (MCI) in a ratio of 1:3, a well-recognized allergenic preservative] was released as an individual preservative in the 2000s for industrial products and in 2005 for cosmetics. The high level of exposure to MI since then has provoked an epidemic of contact allergy to MI, and an increase in MI/MCI allergy. There are questions concerning the MI/MCI cross-reaction pattern. OBJECTIVES: To bring a new perspective on the MI/MCI cross-reactivity issue by studying their in situ chemical behaviour in 3D reconstructed human epidermis (RHE). METHODS: MI and MCI were synthesized with (13) C substitution at positions C-4/C-5 and C-5, respectively. Their in situ chemical behaviours in an RHE model were followed by use of the high-resolution magic angle spinning nuclear magnetic resonance technique. RESULTS: MI was found to react exclusively with cysteine thiol residues, whereas MCI reacted with histidines and lysines. The reaction mechanisms were found to be different for MI and MCI, and the adducts formed had different molecular structures. CONCLUSION: In RHE, different MI/MCI reactions towards different nucleophilic amino acids were observed, making it difficult to explain cross-reactivity between MI and MCI. PMID- 26899806 TI - Thoughts on how to improve the quality of multicentre patch test studies. AB - Multicentre patch test studies (MPTSs) can contribute useful information for diagnostic and preventive measures. The aim of the present paper is to propose how to perform high-quality MPTSs. To this end, factors of significance for the patch test result are discussed with regard to the standardization and calibration of high-quality MPTSs. The 16 factors discussed are scored 0, 1, 2, or 3, depending on the relative importance of a particular factor for the patch test result. The total score of an MPTS allows it to be ranked as having doubtful, acceptable, high or excellent quality. A total score of 30 is possible. Depending on the total score the MPTSs are grouped into those with a doubtful, acceptable, high, and excellent quality. In conclusion, high-quality MPTSs can be performed and are facilitated if a guideline and check list are followed when the study is being planned. The scoring enables the calculation of a total score, which can be used for quality ranking. PMID- 26899807 TI - Allergic contact dermatitis caused by ethylhexylglycerin in both an ointment and a skin aerosol. PMID- 26899808 TI - Further evidence of thioctic acid (alpha-lipoic acid) being a strong cosmetic sensitizer. PMID- 26899809 TI - The danger of wearing dreadlocks at work. PMID- 26899810 TI - A case of allergic contact cheilitis caused by propolis and honey. PMID- 26899811 TI - Allergic contact cheilitis and hand dermatitis caused by a toothpaste. PMID- 26899812 TI - A case of contact urticaria syndrome stage 3 after honey ingestion, induced by epicutaneous sensitization during skin care with honey. PMID- 26899813 TI - Contact allergy to liquorice flavonoids: analysis with liquid chromatography-mass spectrometry. PMID- 26899815 TI - Efficient blue and white polymer light emitting diodes based on a well charge balanced, core modified polyfluorene derivative. AB - Fabrication of efficient blue and white polymer light-emitting diodes (PLEDs) using a well charge balanced, core modified polyfluorene derivative, poly[2,7 (9,9'-dioctylfluorene)-co-N-phenyl-1,8-naphthalimide (99:01)] (PFONPN01), is presented. The excellent film forming properties as observed from the morphological study and the enhanced electron transport properties due to the inclusion of the NPN unit in the PFO main chain resulted in improved device properties. Bright blue light was observed from single layer PLEDs with PFONPN01 as an emissive layer (EML) as well as from double layer PLEDs using tris-(8 hydroxyquinoline) aluminum (Alq3) as an electron transporting layer (ETL) and LiF/Al as a cathode. The effect of ETL thickness on the device performance was studied by varying the Alq3 thickness (5 nm, 10 nm and 20 nm) and the device with an ETL thickness of 20 nm was found to exhibit the maximum brightness value of 11 662 cd m(-2) with a maximum luminous efficiency of 4.87 cd A(-1). Further, by using this highly electroluminescent blue PFONPN01 as a host and a narrow band gap, yellow emitting small molecule, dithiophene benzothiadiazole (DBT), as a guest at three different concentrations (0.2%, 0.4% and 0.6%), WPLEDs with the ITO/PEDOT:PSS/emissive layer/Alq3(20 nm)/LiF/Al configuration were fabricated and maximum brightness values of 8025 cd m(-2), 9565 cd m(-2) and 10 180 cd m(-2) were achieved respectively. 0.4% DBT in PFONPN01 was found to give white light with Commission International de l'Echairage (CIE) coordinates of (0.31, 0.38), a maximum luminous efficiency of 6.54 cd A(-1) and a color-rendering index (CRI) value of 70. PMID- 26899816 TI - The effect of prenatal and intrapartum care on the stillbirth rate among women in rural Ethiopia. AB - OBJECTIVE: To determine whether community-based prenatal and intrapartum care in Ethiopia results in a lower stillbirth rate. METHODS: Between May and December 2014, a randomly selected sample of women in northern and eastern Ethiopia who had delivered a neonate in the preceding 12months completed a face-to-face survey about their experiences of maternal services and the fetal outcome for each delivery. The stillbirth rates among women delivering at home and at health facilities were compared. RESULTS: Overall, 4442 women completed surveys. Stillbirth was reported by 42 (1.7%) of the 2437 women who had received prenatal care and 53 (2.8%) of the 1921 women who did not receive prenatal care (P=0.01). The stillbirth rate was similar among women who delivered in a health center (27/1417 [1.9%]), in a hospital (6/126 [4.8%]), and at home (62/2725 [2.3%]; P=0.13). However, women experiencing an intrapartum emergency were twice as likely to deliver in a health facility (odds ratio 2.6, 95% confidence interval 2.2-3.0). Satisfaction with health-center care was moderately good (median score 77.5/100). CONCLUSION: The stillbirth rate was reduced among women receiving prenatal care, although delivering in a health facility did not reduce the risk of stillbirth. Improving the quality of health-center care could lead to their planned use for childbirth, which might reduce stillbirth rates. PMID- 26899817 TI - Melancholic features in inpatients with major depressive disorder associate with differential clinical characteristics and treatment outcomes. AB - To determine whether the presence of melancholic features in hospitalized patients with major depressive disorder (MDD) was associated with specific clinical characteristics and treatment outcomes, supporting melancholic depression as a distinct subtype within MDD. 126 acutely ill inpatients with MDD were enrolled in an open, 6-week trial with fixed-dose fluoxetine 20mg daily. Symptom severity was assessed regularly, using the 17-item Hamilton Depression Rating Scale (HAMD-17) and Clinical Global Impression of Severity (CGI-S). Melancholic features were defined according to the DSM-IV criteria. Clinical variables were compared between patients with and without melancholic features. Generalized estimating equations method was used to explore the differences in HAMD-17 and CGI-S scores between the 2 groups over time. Clinical response was defined as having a 50% or greater reduction in HAMD-17 scores. 96 (76.2%) of the 126 patients with at least one post-baseline assessment met the criteria for melancholic depression. Melancholic depression differed from non-melancholic depression in clinical characteristics and predicted a better response to fluoxetine treatment. The differentiation between melancholic and non-melancholic depression within MDD hence is clinically significant and valid. PMID- 26899818 TI - Will integrated surveillance systems for vectors and vector-borne diseases be the future of controlling vector-borne diseases? A practical example from China. AB - Vector-borne diseases are one of the world's major public health threats and annually responsible for 30-50% of deaths reported to the national notifiable disease system in China. To control vector-borne diseases, a unified, effective and economic surveillance system is urgently needed; all of the current surveillance systems in China waste resources and/or information. Here, we review some current surveillance systems and present a concept for an integrated surveillance system combining existing vector and vector-borne disease monitoring systems. The integrated surveillance system has been tested in pilot programmes in China and led to a 21.6% cost saving in rodent-borne disease surveillance. We share some experiences gained from these programmes. PMID- 26899819 TI - The Multidimensional Orientation Toward Dying and Death Inventory (MODDI-F): Factorial Validity and Reliability in a U.S. Sample. AB - CONTEXT: Death anxiety has been hypothesized to be a transdiagnostic construct, meaning that the fear of death may increase one's vulnerability to the development or maintenance of a number of psychological disorders. As such, effective and efficient measurement of this construct becomes a priority for hospice and palliative medicine specialists. The Multidimensional Orientation Toward Dying and Death Inventory (MODDI-F) is the only factor-analytically constructed multidimensional scale with a conceptual rationale that measures both the fear and acceptance of dying and death. OBJECTIVES: To determine the factor structure of the MODDI-F with an English-speaking sample, so as to expand the scale's potential for use in hospice and palliative medicine, clinical psychology, and thanatology research. METHODS: Participants comprise a random sample of 404 adults ranging in age from 20 to 85, stratified by sex, age, and ethnicity. They completed the 47-item MODDI-F/eng and were contacted five months later for a test-retest follow-up survey. RESULTS: Although confirmatory factor analyses did not fit the models previously found for the German- and Chinese language versions of the MODDI-F, exploratory factor analyses resulted in a five factor fear dimension and a two-factor acceptance dimension that were empirically and conceptually similar to the German- and Chinese-language versions. Additional psychometric analyses yielded evidence for the internal consistency reliability, five-month test-retest reliability, and construct validity of the seven-factor scores of the English-language MODDI-F. CONCLUSION: The results from this psychometric investigation of the English-language version of the MODDI-F are promising and warrant further investigation with clinical populations in hospice and palliative care settings. PMID- 26899820 TI - Differences in Symptom Burden Among Patients With Moderate, Severe, or Very Severe Chronic Obstructive Pulmonary Disease. AB - CONTEXT: The symptom experience of patients with chronic obstructive pulmonary disease (COPD) is extremely complex. It is characterized by multiple co-occurring symptoms. However, very few studies have described this experience in COPD patients. OBJECTIVES: The aims of this study were to evaluate for differences in symptom occurrence rates, as well as ratings of symptom severity, frequency, and distress among patients (n = 267) with moderate, severe, and very severe COPD. METHODS: The Memorial Symptom Assessment Scale was used to evaluate the multiple dimensions of the patient's symptom experience. Binary and ordinal logistic regression analyses with stage of disease as an ordinal predictor variable were used to evaluate for differences in symptom occurrence rates and ratings of symptom severity, frequency, and distress. RESULTS: Regardless of the severity of their disease, patients reported an average of 12 co-occurring symptoms. Shortness of breath and lack of energy were the only two symptoms that differed significantly among the three disease severity groups in terms of occurrence, severity, frequency, and distress. Patients with very severe COPD reported the highest ratings for shortness of breath and lack of energy across all four symptom dimensions. CONCLUSION: Regardless of stage of disease, the high symptom burden identified in this study underscores the need for COPD patients to be screened for multiple co-occurring symptoms. PMID- 26899821 TI - Chemotherapy Use in the Months Before Death and Estimated Costs of Care in the Last Week of Life. AB - CONTEXT: Considerable attention has been paid to the disproportionately high costs of care for patients nearing death, yet little is known about the costs associated with chemotherapy use among end-stage cancer patients. OBJECTIVES: To compare costs of care other than chemotherapy in the last week of life based on whether cancer patients were using chemotherapy in the months just before death. METHODS: A total of 311 patients with advanced cancer who died between 2002 and 2008 were studied. Data included medical records, patient baseline surveys (median four months before death), and postmortem interviews of caregivers and clinicians. Costs of care were estimated based on reports of death site and services other than chemotherapy received in the week before death (e.g., resuscitation). We tested whether end-of-life (EOL) care preferences, do-not resuscitate order completion, or EOL discussions accounted for relationships between chemotherapy use and estimated care costs. RESULTS: Half (50.5%) of patients were receiving chemotherapy at baseline. Estimated EOL care costs for patients with baseline chemotherapy use (median = $2681) were significantly higher than for patients without baseline chemotherapy use (median = $1092) (P = 0.003). This relationship persisted after adjusting for sociodemographic and clinical characteristics in a generalized linear model (mean incremental cost = $2681, 95% confidence interval $611-$4751, P = 0.01). None of the psychosocial variables accounted for the relationship between chemotherapy use and estimated care costs. CONCLUSION: Chemotherapy for end-stage cancer patients is associated with higher estimated EOL care costs. Given evidence of limited benefit and potential harm of chemotherapy for end-stage cancer patients, the cost effectiveness of such care is questioned and further study warranted. PMID- 26899822 TI - Psychometric Validation of the M. D. Anderson Symptom Inventory-Head and Neck Module in the Spanish Language. AB - CONTEXT: The assessment of cancer-related symptoms requires culturally adapted and psychometrically validated symptom assessment tools. The M. D. Anderson Symptom Inventory-Head and Neck Module (MDASI-HN) is a useful instrument for measuring symptom burden that was specifically developed for head and neck cancer patients. OBJECTIVES: To validate the Spanish version of the MDASI-HN. METHODS: We evaluated the psychometric features of the MDASI-HN in patients with head and neck cancer. We evaluated the item-scale correlations and the internal consistency. We conducted principal axis factoring to identify the underlying dimensions as a measure of construct validity. The convergence/concurrent validity was assessed with the University of Washington Quality of Life Questionnaire for Head and Neck Patients, and known-group validity and test retest reliability also were assessed. RESULTS: One hundred thirty patients were included. The mean +/- SD age was 60.5 +/- 13.6 years; 68% of patients were male, 42% had laryngeal tumors, and 45.9% had Stage III tumors. Forty-seven percent of the patients underwent surgery, 55% underwent radiotherapy, and 36% underwent chemotherapy. The global Cronbach alpha for the HN module was 0.81. The factor analysis identified two factors (Factor 1: speech, mucus, coughing, and constipation; Factor 2: teeth, taste, sores, swallowing, and skin). The correlation with the global score of the University of Washington Quality of Life was -0.68. The difference in the MDASI-HN scores according to Eastern Cooperative Oncology Group performance status was statistically significant (2.72 vs. 4.01, P = 0.006). The intraclass test-retest correlation was 0.62. CONCLUSION: The Spanish version of the MDASI-HN is reliable and valid for evaluating cancer related symptoms in head and neck cancer patients. PMID- 26899823 TI - Pseudobulbar Affect or Depression in Dementia? PMID- 26899824 TI - A novel approach for reliable detection of cathepsin S activities in mouse antigen presenting cells. AB - Cathepsin S (CTSS) is a eukaryotic protease mostly expressed in professional antigen presenting cells (APCs). Since CTSS activity regulation plays a role in the pathogenesis of various autoimmune diseases like multiple sclerosis, atherosclerosis, Sjogren's syndrome and psoriasis as well as in cancer progression, there is an ongoing interest in the reliable detection of cathepsin S activity. Various applications have been invented for specific detection of this enzyme. However, most of them have only been shown to be suitable for human samples, do not deliver quantitative results or the experimental procedure requires technical equipment that is not commonly available in a standard laboratory. We have tested a fluorogen substrate, Mca-GRWPPMGLPWE-Lys(Dnp)-DArg NH2, that has been described to specifically detect CTSS activities in human APCs for its potential use for mouse samples. We have modified the protocol and thereby offer a cheap, easy, reproducible and quick activity assay to detect CTSS activities in mouse APCs. Since most of basic research on CTSS is performed in mice, this method closes a gap and offers a possibility for reliable and quantitative CTSS activity detection that can be performed in almost every laboratory. PMID- 26899825 TI - Distinction between bacterial and viral infections by serum measurement of human neutrophil lipocalin (HNL) and the impact of antibody selection. AB - The distinction between acute infections of bacterial or viral causes is clinically important, but often very difficult even for experienced doctors. Previous studies indicated that serum measurements of HNL (Human Neutrophil Lipocalin) might be a superior diagnostic means in this regard, but also indicated that the antibody conformation of the HNL assay might have an impact on the diagnostic performance. The aim of the present report was to examine this further. METHODS: Several different (n=24) HNL ELISA assays were developed using different combinations of monoclonal and polyclonal HNL antibodies. Sera were collected from healthy persons (n=188) and from 155 patients with acute infections before any antibiotics treatment. The patients were diagnosed as having bacterial (n=69) or viral causes (n=86) of their infections. Plasma and serum were also examined by Western blotting using HNL-specific polyclonal antibodies. RESULTS: The optimal assay format for the distinction between bacterial and viral infection resulted in an area under the receiver operating characteristics curve (AuROC) for S-HNL of 0.98. (95% CI 0.94-1.00) as compared to 0.83 (0.76-0.88) for blood neutrophil counts and 0.69 (0.61-0.76) for S-CRP. Results also showed that different assay formats of HNL identified monomeric and dimeric HNL differently, the monomeric HNL being elevated in viral infections and the dimeric HNL being elevated in bacterial infections. CONCLUSION: We conclude that serum measurement of HNL is a superior diagnostic means to distinguish between acute infections caused by bacteria or virus. For optimal clinical performance the immunoassay should address conformational epitopes in the dimeric HNL. PMID- 26899826 TI - Systematic review of antibiotic consumption in acute care hospitals. AB - Antibiotic consumption is an easily quantifiable performance measure in hospitals and might be used for monitoring. We conducted a review of published studies and online surveillance reports reporting on antibiotic consumption in acute care hospitals between the years 1997 and 2013. A pooled estimate of antibiotic consumption was calculated using a random effects meta-analysis of rates with 95% confidence intervals. Heterogeneity was assessed through subgroup analysis and metaregression. Eighty studies, comprising data from 3130 hospitals, met the inclusion criteria. The pooled rate of hospital-wide consumption was 586 (95% confidence interval 540 to 632) defined daily doses (DDD)/1000 hospital days (HD) for all antibacterials. However, consumption rates were highly heterogeneous. Antibacterial consumption was highest in intensive care units, at 1563 DDD/1000 HD (95% confidence interval 1472 to 1653). Hospital-wide antibacterial consumption was higher in Western Europe and in medium-sized, private and university-affiliated hospitals. The methods of data collection were significantly associated with consumption rates, including data sources, dispensing vs. purchase vs. usage data, counting admission and discharge days and inclusion of low-consumption departments. Heterogeneity remained in all subgroup analyses. Major heterogeneity currently precludes defining acceptable antibiotic consumption ranges in acute care hospitals. Guidelines on antibiotic consumption reporting that will account for case mix and a minimal set of hospital characteristics recommending standardized methods for monitoring and reporting are needed. PMID- 26899827 TI - Pan-genome multilocus sequence typing and outbreak-specific reference-based single nucleotide polymorphism analysis to resolve two concurrent Staphylococcus aureus outbreaks in neonatal services. AB - We used a two-step whole genome sequencing analysis for resolving two concurrent outbreaks in two neonatal services in Belgium, caused by exfoliative toxin A encoding-gene-positive (eta+) methicillin-susceptible Staphylococcus aureus with an otherwise sporadic spa-type t209 (ST-109). Outbreak A involved 19 neonates and one healthcare worker in a Brussels hospital from May 2011 to October 2013. After a first episode interrupted by decolonization procedures applied over 7 months, the outbreak resumed concomitantly with the onset of outbreak B in a hospital in Asse, comprising 11 neonates and one healthcare worker from mid-2012 to January 2013. Pan-genome multilocus sequence typing, defined on the basis of 42 core and accessory reference genomes, and single-nucleotide polymorphisms mapped on an outbreak-specific de novo assembly were used to compare 28 available outbreak isolates and 19 eta+/spa-type t209 isolates identified by routine or nationwide surveillance. Pan-genome multilocus sequence typing showed that the outbreaks were caused by independent clones not closely related to any of the surveillance isolates. Isolates from only ten cases with overlapping stays in outbreak A, including four pairs of twins, showed no or only a single nucleotide polymorphism variation, indicating limited sequential transmission. Detection of larger genomic variation, even from the start of the outbreak, pointed to sporadic seeding from a pre-existing exogenous source, which persisted throughout the whole course of outbreak A. Whole genome sequencing analysis can provide unique fine-tuned insights into transmission pathways of complex outbreaks even at their inception, which, with timely use, could valuably guide efforts for early source identification. PMID- 26899828 TI - Not so bad after all: retroviruses and long terminal repeat retrotransposons as a source of new genes in vertebrates. AB - Viruses and transposable elements, once considered as purely junk and selfish sequences, have repeatedly been used as a source of novel protein-coding genes during the evolution of most eukaryotic lineages, a phenomenon called 'molecular domestication'. This is exemplified perfectly in mammals and other vertebrates, where many genes derived from long terminal repeat (LTR) retroelements (retroviruses and LTR retrotransposons) have been identified through comparative genomics and functional analyses. In particular, genes derived from gag structural protein and envelope (env) genes, as well as from the integrase-coding and protease-coding sequences, have been identified in humans and other vertebrates. Retroelement-derived genes are involved in many important biological processes including placenta formation, cognitive functions in the brain and immunity against retroelements, as well as in cell proliferation, apoptosis and cancer. These observations support an important role of retroelement-derived genes in the evolution and diversification of the vertebrate lineage. PMID- 26899829 TI - Development of a new protocol for rapid bacterial identification and susceptibility testing directly from urine samples. AB - The current gold standard method for the diagnosis of urinary tract infections (UTI) is urine culture that requires 18-48 h for the identification of the causative microorganisms and an additional 24 h until the results of antimicrobial susceptibility testing (AST) are available. The aim of this study was to shorten the time of urine sample processing by a combination of flow cytometry for screening and matrix-assisted laser desorption/ionization time-of flight mass spectrometry (MALDI-TOF-MS) for bacterial identification followed by AST directly from urine. The study was divided into two parts. During the first part, 675 urine samples were processed by a flow cytometry device and a cut-off value of bacterial count was determined to select samples for direct identification by MALDI-TOF-MS at >=5 * 10(6) bacteria/mL. During the second part, 163 of 1029 processed samples reached the cut-off value. The sample preparation protocol for direct identification included two centrifugation and two washing steps. Direct AST was performed by the disc diffusion method if a reliable direct identification was obtained. Direct MALDI-TOF-MS identification was performed in 140 urine samples; 125 of the samples were positive by urine culture, 12 were contaminated and 3 were negative. Reliable direct identification was obtained in 108 (86.4%) of the 125 positive samples. AST was performed in 102 identified samples, and the results were fully concordant with the routine method among 83 monomicrobial infections. In conclusion, the turnaround time of the protocol described to diagnose UTI was about 1 h for microbial identification and 18-24 h for AST. PMID- 26899831 TI - Assessing Medication Problems in those >= 65 Using the STOPP and START Criteria. AB - BACKGROUND: Polypharmacy is a key problem for those >=65. OBJECTIVE: To summarise for individuals >=65 the rates of Potentially Inappropriate Medications (PIMs) identified by application of STOPP, and Potential Prescribing Omissions (PPOs) by START criteria. METHODS: Search: Databases were searched 1980 to 1 December 2015. For Medline the search yielded 3,691 systematic reviews or meta-analyses and 301 when limited to 65 years and over. STOPP.mp yielded 180 citations, START.mp 109,132 and 105 when limited to both. For Embase the search yielded 24,681 systematic reviews or meta-analyses, and 881 when limited to 65+ years. STOPP.mp yielded 427 citations and START.mp 147,322, and 327 when limited to both. RESULTS: Search: identified 28 studies with data and plus a systematic review using STOPP/START criteria. For community dwelling-individuals for national outpatient databases (n=1,528,785) PIMs weighted average was 31%, PPOs 47%. For small community studies (n=2,228) PIMs weighted average was 26%, PPOs 24%. For hospitalised patients (n=4,237) PIMs weighted average was 47%, PPOs 50%. For nursing home patients PIMs weighted average (n=1,539 patients) was 59%, PPOs (n=463 residents) 49%. Principal PIMs were benzodiazepines, proton pump inhibitors, NSAIDs, aspirin, and duplicate medications. Principal PPOs were omissions of medications for cardiovascular diseases, hypertension, osteoporosis, diabetes and hyperlipidemia. CONCLUSIONS: Rates of PIMs and PPOs are high. Criteria are currently based on expert consensus. Next steps are to link criteria to the best internationally-accepted evidence-based systematic reviews/guidelines and conduct RCTs to test whether application of the criteria leads to lower rates of medication errors and hospital admissions. PMID- 26899830 TI - Aspergillus PCR in serum for the diagnosis, follow-up and prognosis of invasive aspergillosis in neutropenic and nonneutropenic patients. AB - We evaluated the usefulness of a serum Aspergillus PCR assay for the diagnosis and prognosis of invasive aspergillosis in a study involving 941 patients for a total of 5146 serum samples. Fifty-one patients had proven/probable aspergillosis. We compared galactomannan (GM), PCR and mycologic analysis of pulmonary samples in both neutropenic and nonneutropenic patients. PCR performed in serum yielded 66.7% sensitivity, 98.7% specificity, 75.6% positive predictive value and 98.0% negative predictive value, while the GM index yielded 78.4% sensitivity, 87.5% specificity, 27% positive predictive value and 98.6% negative predictive value. The inclusion of PCR in the European Organization for Research and Treatment of Cancer (EORTC) and the Mycosis Study Group (MSG) mycologic criteria permitted the reclassification of nine other cases from possible to probable aspergillosis and increased the sensitivity to 71.7%. Combining the GM index with serum PCR increased the detection rate of invasive aspergillosis with 88.2% sensitivity. PCR was systematically negative in 16 patients with noninvasive forms of aspergillosis (namely aspergilloma and chronic aspergillosis). Remaining PCR positive after a period of 14 to 20 days of treatment was related to poor outcome at 30 and 90 days. Our results also indicate that, unlike the determination of the GM index, the initial fungus load as determined by PCR was highly predictive of 90-day mortality, with the rate of the latter being 15.8% for patients with <150 copies/mL vs. 73.2% for patients at or above that cutoff (p <0.0001). Therefore, PCR appears to be a powerful and interesting tool for the identification of patients with invasive aspergillosis who might benefit from more intense care. PMID- 26899833 TI - Cost Implications of Value-Based Pricing for Companion Diagnostic Tests in Precision Medicine. AB - Many interpretations of personalized medicine, also referred to as precision medicine, include discussions of companion diagnostic tests that allow drugs to be targeted to those individuals who are most likely to benefit or that allow treatment to be designed in a way such that individuals who are unlikely to benefit do not receive treatment. Many authors have commented on the clinical and competitive implications of companion diagnostics, but there has been relatively little formal analysis of the cost implications of companion diagnostics, although cost reduction is often cited as a significant benefit of precision medicine. We investigate the potential impact on costs of precision medicine implemented through the use of companion diagnostics. We develop a framework in which the costs of companion diagnostic tests are determined by considerations of profit maximization and cost effectiveness. We analyze four scenarios that are defined by the incremental cost-effectiveness ratio of the new drug in the absence of a companion diagnostic test. We find that, in most scenarios, precision medicine strategies based on companion diagnostics should be expected to lead to increases in costs in the short term and that costs would fall only in a limited number of situations. PMID- 26899832 TI - Systematic Review of Model-Based Economic Evaluations of Treatments for Alzheimer's Disease. AB - BACKGROUND: Numerous economic evaluations using decision-analytic models have assessed the cost effectiveness of treatments for Alzheimer's disease (AD) in the last two decades. It is important to understand the methods used in the existing models of AD and how they could impact results, as they could inform new model based economic evaluations of treatments for AD. OBJECTIVE: The aim of this systematic review was to provide a detailed description on the relevant aspects and components of existing decision-analytic models of AD, identifying areas for improvement and future development, and to conduct a quality assessment of the included studies. METHODS: We performed a systematic and comprehensive review of cost-effectiveness studies of pharmacological treatments for AD published in the last decade (January 2005 to February 2015) that used decision-analytic models, also including studies considering patients with mild cognitive impairment (MCI). The background information of the included studies and specific information on the decision-analytic models, including their approach and components, assumptions, data sources, analyses, and results, were obtained from each study. A description of how the modeling approaches and assumptions differ across studies, identifying areas for improvement and future development, is provided. At the end, we present our own view of the potential future directions of decision-analytic models of AD and the challenges they might face. RESULTS: The included studies present a variety of different approaches, assumptions, and scope of decision-analytic models used in the economic evaluation of pharmacological treatments of AD. The major areas for improvement in future models of AD are to include domains of cognition, function, and behavior, rather than cognition alone; include a detailed description of how data used to model the natural course of disease progression were derived; state and justify the economic model selected and structural assumptions and limitations; provide a detailed (rather than high-level) description of the cost components included in the model; and report on the face-, internal-, and cross-validity of the model to strengthen the credibility and confidence in model results. The quality scores of most studies were rated as fair to good (average 87.5, range 69.5-100, in a scale of 0-100). CONCLUSION: Despite the advancements in decision-analytic models of AD, there remain several areas of improvement that are necessary to more appropriately and realistically capture the broad nature of AD and the potential benefits of treatments in future models of AD. PMID- 26899834 TI - Molecular analysis of DNA in blastocoele fluid using next-generation sequencing. AB - BACKGROUND: Preimplantation genetic testing (PGT) requires an invasive biopsy to obtain embryonic material for genetic analysis. The availability of a less invasive procedure would increase the overall efficacy of PGT. The aim of the study was to explore the potential of blastocoele fluid (BF) as an alternative source of embryonic DNA for PGT. METHODS: Collection of BF was performed by aspiration with a fine needle prior to vitrification. BF DNA was subjected to whole-genome amplification (WGA) and analyzed by high-resolution next-generation sequencing (NGS). RESULTS: A high-quality WGA product was obtained from 8 of 11 (72.7 %) samples. Comparison of matching BF and blastomere samples showed that the genomic representation of sequencing reads was consistently similar with respect to density and regional coverage across the 24 chromosomes. A genome-wide survey of the sample sequencing data also indicated that BF was highly representative of known single gene sequences, and this observation was validated by PCR analyses of ten randomly selected genes, with an overall efficiency of 84 %. CONCLUSION: This study provides further evidence that BF is a promising alternative source of DNA for PGT. PMID- 26899836 TI - Effect of Endothelial Cells on Angiogenic Properties of Multipotent Stromal Cells from the Umbilical Cord during Angiogenesis Modeling in the Basement Membrane Matrix. AB - Short-term cell culturing on basement membrane matrix is a common and very convenient in vitro model of angiogenesis. We studied the possibility of interaction of multipotent stromal cells from the umbilical cord and Ea.hy926 endothelial cells on this model at the early and late periods of the experiment. Multipotent stromal cells alone and in combination with endothelial cells formed an unstable tubular network. Clusters formed after its disassembling later became the sprouting centers in co-culture of the two cell types, but not in pure culture of multipotent stromal cells. Multipotent stromal cells with CD31+ phenotype constitute the structural basis of newly formed stable 3D capillary like network. Prolongation of the time of culturing and combination of the two in vitro models of angiogenesis (tubulogenesis and sprouting) allowed more complete assessment of the angiogenic potential of multipotent stromal cells. PMID- 26899837 TI - Quantitative PCR studies of Aggregatibacter actinomycetemcomitans and Treponema denticola/Tanerella forsythensis Complex as Etiological Factors of Chronic Periodontitis. AB - Real-time quantitative PCR (Dentofl or kit) was used to detect DNA of periodontal pathogens in specimens from 92 patients with chronic periodontitis and from a control sample of 12 normal subjects. A bimodal distribution of patients by periodontium colonization with A. actinomycetemcomitans, P. gingivalis, P. intermedia, T. forsythensis, and T. denticola was demonstrated. A new approach to interpretation of the results of quantitative evaluation of periodontal pathogens, including the notion of pathological colonization level, led to classification of all cases with chronic generalized periodontitis into 3 groups: associated with A. actinomycetemcomitans, with T. forsythensis/T. denticola complex, and cases of uncertain genesis. PMID- 26899835 TI - Mini Mental State Examination and Logical Memory scores for entry into Alzheimer's disease trials. AB - BACKGROUND: Specific cutoff scores on the Mini Mental State Examination (MMSE) and the Logical Memory (LM) test are used to determine inclusion in Alzheimer's disease (AD) clinical trials and diagnostic studies. These screening measures have known psychometric limitations, but no study has examined the diagnostic accuracy of the cutoff scores used to determine entry into AD clinical trials and diagnostic studies. METHODS: ClinicalTrials.gov entries were reviewed for phases II and III active and recruiting AD studies using the MMSE and LM for inclusion. The diagnostic accuracy of MMSE and LM-II cutoffs used in AD trials and diagnostic studies was examined using 23,438 subjects with normal cognition, mild cognitive impairment (MCI), and AD dementia derived from the National Alzheimer's Coordinating Center database. RESULTS: MMSE and LM cutoffs used in current AD clinical trials and diagnostic studies had limited diagnostic accuracy, particularly for distinguishing between normal cognition and MCI, and MCI from AD dementia. The MMSE poorly discriminated dementia stage. CONCLUSIONS: The MMSE and LM may result in inappropriate subject enrollment in large-scale, multicenter studies designed to develop therapeutics and diagnostic methods for AD. PMID- 26899838 TI - New Silk Fibroin-Based Bioresorbable Microcarriers. AB - We fabricated bioresorbable microcarriers from water solution of Bombyx mori silk fi broin. The microcarriers are 3D structures with intricate surface and pores allowing penetration of culture medium, gas exchange, and cell adhesion. Fibroin molecules form hydrophobic structures and normally have a negative charge, which stimulates migration, but inhibits cell adhesion and makes it less effective. In order to improve adhesion efficiency and velocity, gelatin (hydrophilic biopolymer with integrin-recognizing RGD sequence) was added to the microcarrier composition. The resultant bioresorbable microcarriers support adhesion and proliferation of 3T3 murine fibroblasts. PMID- 26899839 TI - Erratum to: Content of HLA-G(+) T Cells in the Peripheral Blood from Healthy Women and Breast Cancer Patients. PMID- 26899840 TI - Characteristics of Multipotent Mesenchymal Stromal Cells Isolated from Human Endometrium. AB - Cell cultures isolated from human endometrium by enzyme digestion consisted of highly viable fibroblast-like mesenchymal cells expressing CD90, CD73, and CD105. During passage 1, the cultures contained a small fraction of cytokeratin-7(+) epithelial cells that disappeared by passage 2. The cultures from the endometrium could be induced to adipogenic, osteogenic and chondrogenic differentiation in vitro. These findings suggest that human endometrium is a convenient source of biomaterial for minimally invasive isolation of cultures that exhibit typical morphology and immunophenotypic profile of resident multipotent mesenchymal stromal cells retain high viability in vitro. PMID- 26899841 TI - Possibility of Using Mesenchymal Stromal Cells to Restore Lymph Flow in Experimental Phlebothrombosis. AB - The possibility of formation of lymphatic vessels after introduction of autologous bone marrow-derived multipotent mesenchymal stromal cells transfected with GFP gene into thrombosed femoral vein was studied by fluorescent microscopy. Vascular thrombosis caused by ligation of the great vein with subsequent injection of thrombin solution was accompanied by blockade of regional lymph flow. The cells injected into thrombosed vein directly participate in the formation of new lymphatic vessels in the paravasal tissue surrounding the vein, its tissue region, and around regional lymph nodes. This is seen from bright specific fluorescence of individual cells in the walls of lymphatic vessels and all vascular layers and valves in UV light. PMID- 26899842 TI - Efficiency of Umbilical Cord Blood Cells in Patients with Treatment-Resistant Depressions. AB - We studied the efficacy of umbilical cord blood cells in the therapy of treatment resistant depressive states in women. Concentrated umbilical cord blood cells were administered in a dose of 250 millions cells (4 injections at 1-week intervals). The control group received placebo. In both groups, reduction of depressive disorders and the decrease in hypothymia severity were observed. Infusions of cell concentrate contributed to delayed correction of treatment resistance and reduced the severity of depression to moderate. In the main group, significant, persistent, and long-term positive dynamics was observed in the cognitive sphere. The therapeutic potential of umbilical cord blood cell concentrate can be used to overcome treatment resistance formed in depressive patients. PMID- 26899843 TI - Comparative Analysis of Proliferation and Viability of Multipotent Mesenchymal Stromal Cells in 3D Scaffolds with Different Architectonics. AB - 3D biodegradable materials (scaffolds) containing bioactive hydroxyapatite molecules fabricated by foaming in supercritical carbon dioxide and by selective laser sintering were used for culturing of mesenchymal stromal cells from the human adipose tissue. Experiments showed that stromal cells from the human adipose tissue adhered and proliferated on all studied types of structures. Addition of hyproxyapatite to the scaffold stimulated proliferation of stromal adipose tissue cells. PMID- 26899844 TI - Effects of Millimeter-Wave Electromagnetic Radiation on the Experimental Model of Migraine. AB - Effects of millimeter-wave electromagnetic radiation (40 GHz frequency, 0.01 mW power) on the spontaneous fi ring of convergent neurons of the spinal trigeminal nucleus and their responses to electrical stimulation of the dura mater were studied in neurophysiological experiments on rats. Irradiation of the area of cutaneous receptive fields of spinal trigeminal nucleus reversibly inhibited both spontaneous discharges and activity induced by electrical stimulation of the dura mater. The second and third exposures to electromagnetic radiation with an interval of 10 min were ineffective. These results suggest that suppression of neuronal excitability in the spinal trigeminal ganglion can be a mechanism of the anti-migraine effects of electromagnetic radiation observed in clinical practice. PMID- 26899845 TI - Structural Characteristics of Gastric Cell Populations in Chronic Gastritis and Chronic Hepatitis under Conditions of Helicobacter pylori Persistence. AB - Helicobacter pylori persistence in patients with chronic gastritis is associated with a complex of nonspecific structural reactions, the type of these reactions correlates with the severity of infection: catarrhal fibrotic changes in the gastric mucosa predominate in cases with manifest colonization, while the absence of H. pylori is associated with predominance of fibrotic process. Analysis of the incidence of some pathomorphological phenomena (degeneration, atrophy, metaplasia, and dysplasia of the surface epithelium) shows no relationship between the presence of H. pylori and colonization intensity. In all patients with chronic hepatitis, the gastric mucosa is involved in the pathological process; fibrosis (gastropathy) was the most common process. No appreciable correlations between the structural changes and hepatitis activity and the presence of H. pylori were detected. PMID- 26899846 TI - Quantitative Evaluation of Changes in the Striatal Astrocyte Axons in Simulated Parkinsonism. AB - Three parkinsonism models using neurotoxin 6-OHDA and pesticides rotenone and paraquat were reproduced in Wistar rats and parameters of astrocyte processes in the striatum (axon number and length, area occupied by them, and axon branching pattern) detected by immunohistochemical reaction for acid glial fibrillary protein were studied by computer morphometry. By these parameters, three morphological types of astrocytes were distinguished. Two variants of changes were found in the used parkinsonism models: 1) more intense branching and even elongation of all axons and 2) reduction of small and elongation of the main remaining stems, which manifested in polarization of glial cell. Type 1 reaction was obviously associated with compensatory increase in astrocyte interaction with neurons, while type 2 reflected astrocyte response to injury and impaired glioneuronal interactions. PMID- 26899847 TI - Variability of the Phenotype and Proliferation and Migration Characteristics of Human Mesenchymal Stromal Cells Derived from the Deciduous Teeth Pulp of Different Donors. AB - We performed a comparative study of cell phenotype and proliferation and migration activities in vitro of mesenchymal stromal cells from human exfoliated deciduous teeth (SHED cells) from three donors. In the primary cultures, the cells of different donors had the same morphology and cytophenotype, but differed by proliferative and migration capacities. The results indicate that individual mesenchymal stromal cells cultures can differ considerably by important cell properties, and this should be considered when evaluating their potential therapeutic efficacy and in experimental studies. PMID- 26899848 TI - Effects of Hypobaric Hypoxia in Various Modes on Expression of Neurogenesis Marker NeuroD2 in the Dentate Gyrus of Rats Hippocampus. AB - The expression of neurogenesis marker--NeuroD2 transcription factor--in the hippocampal dentate gyrus was studied in rats exposed to severe destructive hypoxia, a single or three episodes of moderate hypobaric hypoxia, preconditioned severe hypoxia, and severe hypoxia followed by 3 sessions of postconditioning by moderate hypobaric hypoxia. All the studied hypoxic exposure modes led to an increase of NeuroD2 level. Three-fold moderate hypoxia per se and in the preconditioning mode (followed by exposure to severe hypoxia) produced most pronounced up-regulatory effect on NeuroD2 expression. The results indicated that stimulation of neurogenesis processes seemed to be one of the aspects of the neuroprotective effect of three-fold preconditioning moderate hypoxia, but not of hypoxic postconditioning. PMID- 26899849 TI - The Use of Atomic Force Microscopy for Cytomorphological Analysis of Bacterial Infection Agents. AB - Cytomorphological signs of bacterial infection agents were studied by atomic force microscopy. Analysis of the elastic mechanical characteristics of Staphylococcus spp. from the skin of patients with chronic dermatoses showed lower elasticity of S. aureus cell membrane in comparison with that of transitory flora representatives. Significant differences in characteristics of cell membrane relief and presence of fimA pathogenicity factor were detected in E. coli isolated from the reproductive tract mucosa of clinically healthy women and patients with inflammatory urogenital infections. PMID- 26899850 TI - Effect of Vascular Endothelial Growth Factor and Erythropoietin on Functional Activity of Fibroblasts and Multipotent Mesenchymal Stromal Cells. AB - The study examined the effect of VEGF and erythropoietin on proliferative and migratory activities of skin fibroblasts and multipotent mesenchymal stromal cells of human adipose tissue. VEGF stimulated proliferation and migration of fi broblasts, but produced no significant effect on functional activity of multipotent mesenchymal stem cells. Erythropoietin stimulated proliferation of both cell types, but did not affect their migration. PMID- 26899852 TI - Inflammasome as a New Therapeutic Target for Diabetic Complications. AB - BACKGROUND: Inflammation is an innate immune response which is considered a common basis for several diseases such as ageing, diabetes, obesity, gout, neurodegenerative diseases and others. Among other platforms, inflammasomes are part of a superfamily of Pattern Recognition Receptors (PRR) and act as cytoplasmatic sensors for stimulation with Pathogen Associated Molecular Pattern (PAMPs) and/or Danger/Damage-Associated Molecular Patterns (DAMPs) leading to an infectious/ pathogenic or sterile inflammation. Inflammasomes constitute a complex platform with high molecular weight and functionality, divided into two families: NOD-like or NLR and PYHIN (pyrin and HIN200 - hematopoietic interferoninducible nuclear antigens). After activation by PAMPs or DAMPs, NLRP3 inflammasome promotes conversion of procaspase 1 in caspase-1 to form the active complex which is able to cleave pro-IL-1beta and pro-IL-18 in respective active inflammatory cytokines IL-1beta and IL-18 inducing cellular death by pyroptosis. Diabetes has a very intricate pathology with metabolic adaptation and inflammatory components apparently responsible for diabetic complications. OBJECTIVE: The present review evaluates the role of inflammasome, emphasizing NRLP3 on diabetes. An overview on several inflammatory diseases in which inflammasomes appear to play a role is included. Patents on inflammasomes associated with diabetes are evaluated and discussed. CONCLUSION: There are a significant number of patents on inflammation but few of them are specifically on inflammasome and diabetes. The patents WO2015003246; US20130273588; WO2012016145; and CN104258398 are shown and their mechanisms are discussed. In conclusion, deeply studies on inflammasomes mechanisms will help the proposition of new therapeutic targets for controlling inflammatory process in diabetic complications. PMID- 26899851 TI - Fear of cancer recurrence in survivor and caregiver dyads: differences by sexual orientation and how dyad members influence each other. AB - PURPOSE: The purpose of this study was to identify explanatory factors of fear of recurrence (FOR) in breast cancer survivors of different sexual orientations and their caregivers and to assess the directionality in the survivor and caregiver dyads' FOR. METHODS: We recruited survivors of non-metastatic breast cancer of different sexual orientations and invited their caregivers into this study. Using a telephone survey, we collected data from 167 survivor and caregiver dyads. Using simultaneous equation models and a stepwise selection process, we identified the significant determinants of survivors' and caregivers' FOR and determined the directionality of survivors' and caregivers' FOR. Weighting the model by the inverse propensity score ensured that differences by sexual orientation in age and proportion of life in the caregiver-survivor relationship were accounted for. RESULTS: Caregivers' FOR predicted survivors' FOR, and sexual orientation had a significant effect on survivors' FOR, in that sexual minority women reported less FOR than heterosexual women. Other determinants of survivors' FOR included their medical characteristics, coresidence with caregivers, and caregivers' social support and use of counseling. Caregivers' FOR was related to their social support and survivors' medical characteristics. CONCLUSIONS: This study suggests a need for caregiver interventions. Because survivors' FOR is affected by caregivers' FOR, caregiver interventions will likely benefit survivors' FOR. IMPLICATIONS FOR CANCER SURVIVORS: Both sexual minority and heterosexual breast cancer survivors' FOR are affected by their caregivers' FOR, which suggests that the caregivers of breast cancer survivors are central for the survivors' well-being and shall therefore be integrated into the care process. PMID- 26899853 TI - Antibacterial and Antiinflammatory Properties of Bovine Colostrum. AB - CONTEXT: Immunity related disorder is one of the leading causes of disease in the world. Oxidative stress and microbial infections play a major role in inflammation-induced diseases. Bovine colostrum (BC) contains immunoglobulins and lactoferrins which help in building the immunity and protect against the bacterial proliferation and growth. AIM: This study was designed to investigate the antimicrobial and antiinflammatory activities of BC. MATERIALS AND METHODS: Antimicrobial activity was determined by the pour-plate method using five different strains of bacteria (Gram -ve and +ve), and carrageenan-induced rat paw edema method was used for the evaluation of antiinflammatory activity in adult Wistar rats. Diclofenac was used as standard antiinflammatory drug, and amoxicillin was used as standard antimicrobial agent. RESULTS: BC showed significant antimicrobial activity against Escherichia. coli, Staphylococcus. aureus, Proteus. vulgaris, Enterobacter. aerogenes and Salmonella. typhi. At 100 ug/mL of BC, the inhibition zones were found to be 13mm, 11mm, 12mm, 12mm, and 11mm, respectively. The BC zones were comparatively smaller than those of amoxicillin at 10ug/mL, where the inhibition zones were 16mm, 30mm, 23mm, 22mm and 23mm, respectively. In the BC treated animals, the percentage edema inhibition was found to be 67.94% at the third hour, suggesting high antiinflammatory activity of BC in rats. CONCLUSION: BC may be beneficial in reducing the risks of inflammation associated diseases. Further studies are needed before BC can be recommended for therapeutic interventions in humans. PMID- 26899854 TI - PPCPs in Jiulong River estuary (China): Spatiotemporal distributions, fate, and their use as chemical markers of wastewater. AB - The occurrence and fate of 50 pharmaceuticals and personal care products (PPCPs) were investigated in the surface water of Jiulong River estuary in the southeast of China in spring, wet season, summer, autumn and winter. Results demonstrated a wide distribution of PPCPs in Jiulong River estuary, where 34 PPCPs were detected at least once and 5 PPCPs were detected in all the samples, including caffeine, diclofenac, metoprolol, methyl paraben, and propyl paraben. Spatial and seasonal variations were observed. Special emphasis was placed on the PPCP fate in the estuary. Most PPCPs showed a non-conservative behavior in the estuary, while the non-steroidal anti-inflammatory drugs and bisphenol A showed a pseudo conservative behavior. The non-conservative and pseudo-conservative behavior was attributed to the combination of the seawater dilution, the introduction of PPCPs via the sewage water, and the physical, chemical, or biological removal processes. Furthermore, PPCP concentrations showed drastic variations in the turbidity maximum zones. To our best knowledge, this is the first work to indicate the pseudo-conservative behavior of PPCPs in the estuary, and to show the drastic variations of PPCPs in the turbidity maximum zone. In addition, the ratio of labile to conservative PPCPs was calculated to track the source of untreated sewage contamination. Results showed a significantly higher ratio compared to the average value in WWTP effluents, indicating the ubiquitous discharge of untreated domestic wastewater in Jiulong River estuary. In addition, the high ratio of bisphenol A to conservative PPCPs implied the potential input of untreated industrial wastewater in Jiulong River estuary. PMID- 26899855 TI - Cu2O loaded titanate nanotube arrays for simultaneously photoelectrochemical ibuprofen oxidation and hydrogen generation. AB - A p-n junction Cu2O doped TiO2 nanotube arrays (Cu2O/TNAs) were synthesized by square wave voltammetry electrochemical (SWVE) deposition method and employed as the working anode. The crystalline, optical properties, surface morphology, and structure of the Cu2O/TNAs were characterized by XRD, UV-vis absorbance edges, SEM, and XPS. Results showed that the Cu2O/TNAs were dominated by anatase phase after sintering at 450 degrees C with significant visible light response. XPS finding confirmed XRD results that the copper element in Cu2O/TNAs was Cu (I) instead of Cu (II). SEM images illustrated the diameter and the length of supported TiO2 nanotubes was approximately 100 nm and 2.75-4.34 MUm, respectively. After Cu2O doping, the nano-tubular structure of TiO2 nanotube kept its integrity with no significant morphological change, which was beneficial for PEC applications. The photocurrent of Cu2O/TNAs was 1.45 times larger than that of TNAs, implying that Cu2O doping significantly enhanced electron mobility by reducing the recombination of electron-hole pairs. In addition, electrochemical impedance spectroscopy (EIS) measurements revealed that the recombination of photogenerated electron-hole pairs was inhibited as the bias potential was applied. Results of Bode plot further demonstrated that the electron lifetime tauel of Cu2O/TNAs-20 (30.79 ms), under 0.5 V bias potential, was about 2.23 times higher than that of pure TNAs (13.82 ms). Results of electron spin resonance (ESR) analyses demonstrate that the hydroxyl radicals (OH) are responsible for the PEC decomposition of Ibuprofen. PMID- 26899856 TI - Guest Editorial: Inherited bone marrow failure and myelodysplasia in children: how much do we know about pediatric diseases? PMID- 26899858 TI - Unresolved grief and its consequences. A nationwide follow-up of teenage loss of a parent to cancer 6-9 years earlier. AB - PURPOSE: The early loss of a parent is a tragedy and a serious life event. This study investigated grief resolution and morbidity in cancer-bereaved teenagers 6 to 9 years after the loss of a parent to cancer. METHODS: In a nationwide population-based study of 622 of 851 (73 %) youths who as teenagers 6 to 9 years earlier had lost a parent to cancer, we explored the magnitude of unresolved grief and its association with psychological and physiological morbidity. Participants answered a study-specific anonymous questionnaire including questions about if they had worked through their grief and about their current health. RESULTS: Six to nine years post-loss 49 % reported unresolved grief (8 % no and 41 % a little grief resolution). They had, in comparison with youths reporting resolved grief, statistically significantly elevated risks, e.g. for insomnia (sons' relative risk (RR) 2.3, 95 % CI 1.3-4.0; daughters' RR 1.7, 95 % CI 1.1-2.7), fatigue (sons' RR 1.8, 95 % CI 1.3-2.5; daughters' RR 1.4, 95 % CI 1.1-1.7) and moderate to severe depression, i.e. score >9, PHQ-9 (sons' RR 3.6, 95 % CI 1.4-8.8; daughters' RR 1.8, 95 % CI 1.1-3.1). Associations remained for insomnia in sons, exhaustion in daughters and fatigue in both sons and daughters when depression, negative intrusive thoughts and avoiding reminders of the parents' disease or death were included in a model. CONCLUSIONS: Approximately half of cancer-bereaved youth report no or little grief resolution 6 to 9 years post-loss, which is associated with fatigue, sleeping problems and depressive symptoms. PMID- 26899859 TI - The characteristics and occurrence of the talon cusps in Turkish population: a retrospective sample study. AB - PURPOSE: The purpose of this study was to figure out the characteristics and occurrence of talon cusps in a sample of Turkish population. METHODS: In this retrospective study, talon cusps in permanent dentition were evaluated on radiographs and intraoral photographs which were obtained from patients who were referred to Oral and Maxillofacial Radiology Department, Faculty of Dentistry, Adnan Menderes University, Aydin, Turkey between January 2013 and January 2014. RESULTS: Talon cusps were observed in 365 of 4116 patients, with a frequency of 8.86 %. There were 208 (57 %) females and 157 (43 %) males with this variation. Maxillary canines were the most affected anterior teeth (40.83 %), followed by lateral incisors (39.60 %) and central incisors (19.55 %). Of the patients, 81 (22.19 %) had type I talon cusp with two periapical pathologies, 114 (31.23 %) had type II talon cusp with four periapical pathologies and 226 (61.91 %) had type III talon cusp with also four periapical pathologies. CONCLUSIONS: The occurrence of talon cusps was higher than other studies reported in the literature, with an exception of the study in Alaskan Eskimos. The most commonly detected type of talon cusp was type III (61.91 %), and dens invaginatus was the most frequent variation observed with talon cusps. PMID- 26899857 TI - Human polyomaviruses and incidence of cutaneous squamous cell carcinoma in the New Hampshire skin cancer study. AB - Squamous cell carcinoma (SCC) of the skin is a malignancy arising from epithelial keratinocytes. Experimental and epidemiologic evidence raise the possibility that human polyomaviruses (PyV) may be associated with the occurrence of SCC. To investigate whether the risk for SCC was associated with PyV infection, seropositivity to 10 PyV types was assessed following diagnosis in a population based case-control study conducted in the United States. A total of 253 SCC cases and 460 age group and gender-matched controls were included. Antibody response against each PyV was measured using a multiplex serology-based glutathione S transferase capture assay of recombinantly expressed VP1 capsid proteins. Odds ratios (OR) for SCC associated with seropositivity to each PyV type were estimated using logistic regression, with adjustment for potentially confounding factors. SCC cases were seropositive for a greater number of PyVs than controls (P = 0.049). Those who were JC seropositive had increased odds of SCC when compared to those who were JC seronegative (OR = 1.37, 95% CI: 0.98-1.90), with an increasing trend in SCC risk with increasing quartiles of seroreactivity (P for trend = 0.04). There were no clear associations between SCC risk and serostatus for other PyV types. This study provides limited evidence that infection with certain PyVs may be related to the occurrence of SCC in the general population of the United States. PMID- 26899860 TI - Seroepidemiology of HTLV-1 and HTLV-2 Infection in Neyshabur City, North-Eastern Iran, during 2010-2014. AB - BACKGROUND: Retroviruses of human T-lymphotropic viruses (HTLV-1 and HTLV-2) have been demonstrated to be endemic in the north-eastern region of Iran. This study was aimed to determine the HTLV-1 and HTLV-2 prevalence among healthy individuals in Neyshabur City during 2010-2014. METHODS: A total of 8054 blood samples were collected from healthy participants in Neyshabur, North-Eastern Iran. The blood samples were screened for the presence of specific antibodies against HTLV-1 and HTLV-2 by using ELISA according to the manufacturer's instructions. RESULTS: The overall seropositivity rate for HTLV-1 and HTLV-2 was found to be 6.55% (528 out of 8054) among participants. CONCLUSION: Both HTLV-1 and HTLV-2 were demonstrated to be at a high rate in healthy individuals. However, a smaller number of asymptomatic carriers were found in this study, as compared to those identified in previous investigations in the city. PMID- 26899861 TI - Modulation of Candida albicans Biofilm by Different Carbon Sources. AB - In the present investigation, the role of carbon sources (glucose, lactate, sucrose, and arabinose) on Candida albicans biofilm development and virulence factors was studied on polystyrene microtiter plates. Besides this, structural changes in cell wall component beta-glucan in presence of different carbon sources have also been highlighted. Biofilm formation was analyzed by XTT (2,3 bis[2-Methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide) reduction assay. Glucose-grown cells exhibited the highest metabolic activity during adhesion among all carbon sources tested (p < 0.05). However, cells exposed to sucrose exhibited highest biofilm formation and matrix polysaccharides secretion after 48 h. The results also correlated with the biofilm height and roughness measurements by atomic force microscopy. Exposure to lactate induced hyphal structures with the highest proteinase activity while arabinose-grown cells formed pseudohyphal structures possessing the highest phospholipase activity. Structural changes in beta-glucan characterized by Fourier transform infrared (FTIR) spectroscopy displayed characteristic band of beta-glucan at 892 cm(-1) in all carbon sources tested. The beta(1->6) to beta(1->3) glucan ratio calculated as per the band area of the peak was less in lactate (1.15) as compared to glucose (1.73), sucrose (1.62), and arabinose (2.85). These results signify that carbon sources influence C. albicans biofilm development and modulate virulence factors and structural organization of cell wall component beta-glucan. PMID- 26899862 TI - Perineural versus intravenous dexamethasone as adjuncts to local anaesthetic brachial plexus block for shoulder surgery. AB - This randomised, double-blind, placebo-controlled study compared the effect of perineural with intravenous dexamethasone, both administered concomitantly with interscalene brachial plexus block for shoulder surgery. Patients received 8 mg dexamethasone mixed with ropivacaine in the block injection (n = 42), 8 mg dexamethasone intravenously at the time of the block (n = 37), or intravenous saline (n = 41) at the time of the block. Perineural and intravenous dexamethasone resulted in prolonged mean (SD) duration of block to 16.9 (5.2) h and 18.2 (6.4) h, respectively, compared with 13.8 (3.8) h for saline (p = 0.001). Mean (SD) opioid consumption (morphine equivalents) during the first 24 h after postanaesthesia recovery arrival was 12.2 (9.3) mg in the perineural dexamethasone, 17.1 (15.9) mg in the intravenous dexamethasone and 24.1 (14.3) mg in the saline groups (p = 0.001). Dexamethasone via either route reduced anti emetic use (p = 0.046). There was no effect on patient satisfaction. These results suggest that both perineural and intravenous dexamethasone are useful adjuncts to ropivacaine interscalene block, with the intravenous route preferred as this avoids the possibility of neural toxicity of dexamethasone. PMID- 26899865 TI - Editorial for Special Issue on Chemical Complexity and Biology. PMID- 26899863 TI - Transportan 10 improves the anticancer activity of cisplatin. AB - The aim of this paper was to examine whether cell-penetrating peptides (CPPs) such as transportan 10 (TP10) or protein transduction domain (PTD4) may improve the anticancer activity of cisplatin (cPt). The complexes of TP10 or PTD4 with cPt were used in the experiments. They were carried out on two non-cancer (HEK293 (human embryonic kidney) and HEL299 (human embryo lung)) and two cancer (HeLa (human cervical cancer) and OS143B (human osteosarcoma 143B)) cell lines. Both complexes were tested (MTT assay) with respect to their anticancer or cytotoxic actions. TAMRA (fluorescent dye)-stained preparations were visualized in a fluorescence microscope. The long-term effect of TP10 + cPt and its components on non-cancer and cancer cell lines was observed in inverted phase contrast microscopy. In the MTT test (cell viability assay), the complex of TP10 + cPt produced a more potent effect on the cancer cell lines (HeLa, OS143B) in comparison to that observed after separate treatment with TP10 or cPt. At the same time, the action of the complex and its components was rather small on non cancer cell lines. On the other hand, a complex of another CPP with cPt, i.e., PTD4 + cPt, was without a significant effect on the cancer cell line (OS143B). The images of the fluorescent microscopy showed TAMRA-TP10 or TAMRA-TP10 + cPt in the interior of the HeLa cells. In the case of TAMRA-PTD4 or TAMRA-PTD4 + cPt, only the first compound was found inside the cancer cell line. In contrast, none of the tested compounds gained access to the interior of the non-cancer cells (HEK293, HEL299). Long-term incubation with the TP10 + cPt (estimated by inverted phase contrast microscopy) lead to an enhanced action of the complex on cell viability (decrease in the number of cells and change in their morphology) as compared with that produced by each single agent. With regard to the tested CPPs, only TP10 improved the anticancer activity of cisplatin if both compounds were used in the form of a complex. Additionally, the complex was relatively safe for non-cancer cells. What is more, TP10 also produced an anticancer effect on HeLa and OS143B cell lines. PMID- 26899866 TI - Inferring the determinants of protein evolutionary rates in mammals. AB - Understanding the determinants of protein evolutionary rates is one of the most fundamental evolutionary questions. Previous studies have revealed that many biological variables are tightly associated with protein evolutionary rates in mammals. However, the dominant role of these biological variables and their combinatorial effects to evolutionary rates of mammalian proteins are still less understood. In this work, we derived a quantitative model to correlate protein evolutionary rates with the levels of these variables. The result showed that only a small number of variables are necessary to accurately predict protein evolutionary rates, among which miRNA regulation plays the most important role. Our result suggested that biological variables are extensively interrelated and suffer from hidden redundancies in determining protein evolutionary rates. Various variables should be considered in a natural ensemble to comprehensively assess the determinants of protein evolutionary rate. PMID- 26899867 TI - A novel approach to investigation of the pathogenesis of pterygium based on assessment of promoter hyper-methylation and expression profile of CTLA4 gene: A credible report of CTLA4 gene expression in human eye tissue. AB - BACKGROUND: Pterygium is the human eye lesion whose prevalence in the general population is estimated about 2%. The disease, in extreme phase, can lead to visual disturbance and eventually causes complete loss of vision due to the lesion growth over the papillary axis. Pterygium invasive tissue is a tumor-like tissue that is initially identified and then is attacked by cytotoxic T cells. Cytotoxic T lymphocyte associated antigen 4 (CTLA4), as a modulator molecule of the adaptive immune system, plays a critical role in maintaining peripheral T cell tolerance by diminishing its responsiveness and increasing its activation threshold. The aim of this study is to investigate the association between some epigenetic changes of the CTLA4 gene, such as promoter methylation and gene expression, and pathogenesis of pterygia. MATERIALS AND METHODS: Genomic DNA was extracted from 75 formalin-fixed, paraffin-embedded tissues of pterygia and 70 specimens of normal conjunctiva from eyes without pterygium as the control group, collected from Sistan and Baluchestan population. CTLA4 gene promoter methylation was carried out by methylation-specific PCR technique. The gene expression analysis was done on extracted total RNA from 20 healthy and 23 pterygium tissue samples using Real-Time PCR technique. RESULTS: Promoter methylation changes of CTLA4 gene were not statistically different in patients with pterygium in comparison with healthy controls (OR=1.614; 95% CI=0.57-4.75; P value=0.37). However, gene expression level of CTLA4 was remarkably different in patients and healthy controls (Mean+/-SD: 1.343+/-0.133 and 2.027+/-0.219, respectively; P value=0.009). CONCLUSION: This is a credible evidence of CTLA4 gene expression in human eye tissue. This first hand attempt of investigating the association of epigenetic changes of the CTLA4 gene and pathogenesis of pterygia, indicated a significant intensification of the gene expression of CTLA4 in patients with pterygia. We suggest that increasing CTLA4 gene expression can be a trigger which promotes pterygium enlargement. However, further studies on more populations with larger sample sizes need to be done to verify this hypothesis in the future. PMID- 26899864 TI - Reduction of autophagy markers mediated protective effects of JNK inhibitor and bucladesine on memory deficit induced by Abeta in rats. AB - Autophagy, the process of self-degradation of cellular components, has an important role in neurodegenerative diseases, such as Alzheimer's disease. In this study, we investigated the effects of SP600125 as c-Jun N-terminal kinase (JNK) inhibitor and bucladesine as a cyclic adenosine 3',5'-monophosphate (cAMP) analog on spatial memory and expression of autophagic factors in Abeta-injected rats. Male Wistar rats were used. Rats were randomly allocated into five groups as following: amyloid beta (Abeta)-only group, Abeta + SP600125 (30 MUg/1 MU/side, n = 7) and/or bucladesine (100 MUM/1 MUl/side, n = 7), and the normal control (vehicle only) group. The treatments were administered bilaterally to the CA1 sub-region of the hippocampus stereotaxically. Spatial reference memory was performed using Morris Water Maze 21 days later. The expression of authophagy markers (beclin1, Atg7, Atg12, and LC3 II/LC3 I) in the hippocampus was evaluated using western blotting. Compared to the vehicle group, Abeta administration reduced spatial reference learning (P < 0.001) and memory (P < 0.01) and upregulated the expression of beclin1, Atg7, Atg12, and LC3 II/I (P < 0.0001). Compare to Abeta-only group, the administration of SP600125 and/or bucladesine improved spatial reference learning (P < 0.001) and memory (P < 0.01). Compared to the Abeta-only group, the treatment with SP600125 and/or bucladesine also reduced beclin1, Atg7, Atg12, and LC3 II/I (P < 0.0001) which was similar to amount of normal rats. In summary, it seems that the improvement of spatial memory by SP600125 and/or bucladesine in Abeta-injected rats is in relation with normalizing of autophagy to the physiologic level, possibly through neuroprotection and/or neuroplasticity. PMID- 26899868 TI - Fractality and entropic scaling in the chromosomal distribution of conserved noncoding elements in the human genome. AB - Conserved non-coding elements (CNEs) are defined using various degrees of sequence identity and thresholds of minimal length. Their conservation frequently exceeds the one observed for protein-coding sequences. We explored the chromosomal distribution of different classes of CNEs in the human genome. We employed two methodologies: the scaling of block entropy and box-counting, with the aim to assess fractal characteristics of different CNE datasets. Both approaches converged to the conclusion that well-developed fractality is characteristic of elements that are either extremely conserved between species or are of ancient origin, i.e. conserved between distant organisms across evolution. Given that CNEs are often clustered around genes, we verified by appropriate gene masking that fractal-like patterns emerge even when elements found in proximity or inside genes are excluded. An evolutionary scenario is proposed, involving genomic events that might account for fractal distribution of CNEs in the human genome as indicated through numerical simulations. PMID- 26899869 TI - Expression of recombinant human alpha-lactalbumin in milk of transgenic cloned pigs is sufficient to enhance intestinal growth and weight gain of suckling piglets. AB - Human alpha-lactalbumin (HLA) has very high nutritional value and important physiological functions during the neonatal period. The peptides derived from HLA provide diverse health benefits including antimicrobial, antiviral, immune modulating, and antihypertensive effects. Thus, it is worth investigating the effects on offspring development of increasing HLA in milk. In this study, we found that recombinant human alpha-lactalbumin (rHLA) exhibits efficient inhibition of dipeptidyl peptidase-IV (DPP-IV) activity in an in vitro simulated gastrointestinal digestion system. Using a BAC clone containing the complete HLA gene as a candidate vector, we generated two lines of transgenic cloned sows via somatic cell nuclear transfer that over-expressed rHLA. The average concentrations of rHLA in milk from the two lines of transgenic cloned sows were 2.24 +/- 0.71 mg/ml and 2.67 +/- 1.29 mg/ml. The feeding experiments revealed that rHLA represses dipeptidyl peptidase-IV (DPP-IV) activity in vivo. Furthermore, the piglets reared by rHLA transgenic cloned sows exhibit better performance in gain of body weight and intestine growth than the control piglets reared by non-transgenic sows. Therefore, these findings indicate that rHLA could serve as a natural precursor for a DPP-IV inhibitor, and the transgenic technology that produced the over-expression of rHLA could be a useful method for pig breeders to improve lactation performance. PMID- 26899870 TI - Dysregulation of miRNA isoform level at 5' end in Alzheimer's disease. AB - Alzheimer's disease (AD) is the most common form of dementia, whose mechanism is still not yet fully understood. A miRNA-based signature method, commonly according to the changes of expression levels, is widely used for AD analysis in previous studies. Recently, miRNA isoforms called as isomiR variants, which is considered to play important biological roles, have been demonstrated as the applications of high throughput sequencing platforms. Here, we presented an entropy-based model to detect the miRNA isoform level at the 5' end, and found many miRNAs with significant changes of isoform levels between the early stage and the late stage of AD by the application of this model to the public data. The statistical significance of the overlap between isoform-level changed miRNAs and AD related miRNAs extracted from HMDD2 supports that these miRNA isoforms are not degradation products. Based on the most common isomiR seed analysis of isoform level changed AD related miRNAs, the predicted targets are also found to be enriched for genes involved in transcriptional regulation and the nervous system. After comparing with the expression level based method, we detected that changes of 5' isoform levels are more stable than those of expression levels for AD related miRNA detecting. PMID- 26899871 TI - Identification of ten mevalonate enzyme-encoding genes and their expression in response to juvenile hormone levels in Leptinotarsa decemlineata (Say). AB - The mevalonate pathway is responsible for the biosynthesis of many essential molecules important in insect development, reproduction, chemical communication and defense. Based on Leptinotarsa decemlineata transcriptome and genome data, we identified ten genes that encoded acetoacetyl-CoA thiolase (LdAACT1 and LdAACT2), hydroxymethylglutaryl (HMA)-CoA synthase (LdHMGS), HMG-CoA reductase (LdHMGR1 and LdHMGR2), mevalonate kinase (LdMevK), phospho-mevalonate kinase (LdPMK), mevalonate diphosphate decarboxylase (LdMDD), isopentenyl-diphosphate isomerase (LdIDI) and farnesyl pyrophosphate synthetase (LdFPPS). Nine of these genes (except for LdAACT1) were mainly expressed in the larval brain-corpora cardiaca corpora allata complex, and adult ovary and testis. The 9 genes were transcribed at high levels right after each ecdysis, and at low levels in the mid instar. Therefore, the 9 genes were indicated to be involved in JH biosynthesis. Moreover, knockdown of a JH biosynthesis gene LdJHAMT to lower JH titer significantly downregulated the transcription of the 9 genes. Ingestion of JH to activate JH signaling also significantly suppressed the expression of the 9 genes. It appears that the accumulation of JH precursors in LdJHAMT RNAi larvae and a high JH titer in JH-fed specimens may cause negative feedbacks to repress the expression of the 9 mevalonate enzyme-encoding genes (excluding LdAACT1) to balance the enzyme quantity in L. decemlineata. PMID- 26899872 TI - Anti-obesity effects of artificial planting blueberry (Vaccinium ashei) anthocyanin in high-fat diet-treated mice. AB - This study aimed to evaluate the anti-obesity effects of artificial planting blueberry (Vaccinium ashei) anthocyanin (BA) in high-fat diet-induced obese male C57BL/6 mice. BA at doses of 50, 100, and 200 mg/kg was supplemented in the daily food of obese C57BL/6 mice during an 8-week experiment. Our findings indicate that consumption of BA at high doses reduced body weight by 19.4%, whereas both low and middle doses did not affect the body weight. Furthermore, BA supplementation at high dose could effectively decrease serum glucose, attenuate epididymal adipocytes, improve lipid profiles, and significantly down-regulate expression levels of TNFalpha, IL-6 PPARgamma, and FAS genes. Therefour, BA might alter bodyweight by suppressing fatty acid synthesis and alleviating inflammation. PMID- 26899875 TI - Comproportionation Synthesis of Copper(I) Alkynyl Complexes Encapsulating Polyoxomolybdate Templates: Bowl-Shaped Cu33 and Peanut-Shaped Cu62 Nanoclusters. AB - Comproportionation reaction of Cu(II) salt and copper metallic powder in the presence of tert-butylacetylene (tBuC=CH) in methanol at room temperature yielded discrete Cu(I) tert-butylethynide clusters whose identity depended on the particular co-existing anion employed. Introduction of polyoxomolybdate to the reaction system afforded two new core-shell nanoclusters, [Cu33(tBuC=C)24(Mo4O16)].BF4 (3) and [Cu62(tBuC=C)34(Mo5O19)2(MoO4)2(OTf)2(OH)4].(OTf)2 (4). Complexes 3 and 4 represent the first examples of high-nuclearity Cu(I) clusters that encapsulate polyoxometalate templates, and the latter features the largest Cu(I) alkynyl cluster known to date. The present study not only demonstrates a new paradigm for the designed synthesis of Cu(I) alkynyl clusters but also opens the door to understanding Cu(I) alkynyl structural chemistry. PMID- 26899874 TI - Cell-free ribosome display and selection of antibodies on arrayed antigens. AB - In vitro display technology is a powerful tool for discovery and optimisation of novel antibodies. With increasing demands on various binding molecules in proteomics studies, techniques for a large-scale generation of antibodies or antibody fragments are needed. Here, we describe a novel method for parallel generation of different antibody fragments (scFv) by integrating cell-free ribosome display with array technology. We have demonstrated the procedure by successfully isolating scFv antibodies specific to 16 different cancer biomarkers via a single process. Our results provide proof of principle for multiple production of various scFv antibodies simultaneously. PMID- 26899873 TI - Activated FXR Inhibits Leptin Signaling and Counteracts Tumor-promoting Activities of Cancer-Associated Fibroblasts in Breast Malignancy. AB - Cancer-associated fibroblasts (CAFs), the principal components of the tumor stroma, play a central role in cancer development and progression. As an important regulator of the crosstalk between breast cancer cells and CAFs, the cytokine leptin has been associated to breast carcinogenesis. The nuclear Farnesoid X Receptor-(FXR) seems to exert an oncosuppressive role in different tumors, including breast cancer. Herein, we demonstrated, for the first time, that the synthetic FXR agonist GW4064, inhibiting leptin signaling, affects the tumor-promoting activities of CAFs in breast malignancy. GW4064 inhibited growth, motility and invasiveness induced by leptin as well as by CAF-conditioned media in different breast cancer cell lines. These effects rely on the ability of activated FXR to increase the expression of the suppressor of the cytokine signaling 3 (SOCS3) leading to inhibition of leptin-activated signaling and downregulation of leptin-target genes. In vivo xenograft studies, using MCF-7 cells alone or co-injected with CAFs, showed that GW4064 administration markedly reduced tumor growth. Interestingly, GW4064-treated tumors exhibited decreased levels of leptin-regulated proteins along with a strong staining intensity for SOCS3. Thus, FXR ligands might represent an emerging potential anti-cancer therapy able to block the tumor supportive role of activated fibroblasts within the breast microenvironment. PMID- 26899876 TI - Computer-aided multiple-head 3D printing system for printing of heterogeneous organ/tissue constructs. AB - Recently, much attention has focused on replacement or/and enhancement of biological tissues via the use of cell-laden hydrogel scaffolds with an architecture that mimics the tissue matrix, and with the desired three dimensional (3D) external geometry. However, mimicking the heterogeneous tissues that most organs and tissues are formed of is challenging. Although multiple-head 3D printing systems have been proposed for fabricating heterogeneous cell-laden hydrogel scaffolds, to date only the simple exterior form has been realized. Here we describe a computer-aided design and manufacturing (CAD/CAM) system for this application. We aim to develop an algorithm to enable easy, intuitive design and fabrication of a heterogeneous cell-laden hydrogel scaffolds with a free-form 3D geometry. The printing paths of the scaffold are automatically generated from the 3D CAD model, and the scaffold is then printed by dispensing four materials; i.e., a frame, two kinds of cell-laden hydrogel and a support. We demonstrated printing of heterogeneous tissue models formed of hydrogel scaffolds using this approach, including the outer ear, kidney and tooth tissue. These results indicate that this approach is particularly promising for tissue engineering and 3D printing applications to regenerate heterogeneous organs and tissues with tailored geometries to treat specific defects or injuries. PMID- 26899877 TI - Regulatory development of geriatric medicines: To GIP or not to GIP? AB - Geriatric patients represent the main users of medicines, but are historically often minimally included in clinical trials, resulting in a gap in the knowledge of the benefit/risk balance of medicines in this heterogeneous population. As the worldwide population is aging, the need for safe and effective medicines for older patients is proportionally increasing. The aim of this review is to provide an overview of the current regulatory status of the development of geriatric medicines, the encountered challenges and the view of the involved stakeholders, coming to the conclusion whether it is necessary or not to implement a Geriatric Investigation Plan (GIP), by analogy with pediatrics. PMID- 26899878 TI - Comparative Proteomic Study of Fatty Acid-treated Myoblasts Reveals Role of Cox-2 in Palmitate-induced Insulin Resistance. AB - Accumulated studies demonstrate that saturated fatty acids (FAs) such as palmitic acid (PA) inhibit insulin signaling in skeletal muscle cells and monounsaturated fatty acids such as oleic acid (OA) reverse the effect of PA on insulin signaling. The detailed molecular mechanism of these opposite effects remains elusive. Here we provide a comparative proteomic study of skeletal myoblast cell line C2C12 that were untreated or treated with PA, and PA plus OA. A total of 3437 proteins were quantified using SILAC in this study and 29 proteins fall into the pattern that OA reverses PA effect. Expression of some these proteins were verified using qRT-PCR and Western blot. The most significant change was cyclooxygenase-2 (Cox-2). In addition to whole cell comparative proteomic study, we also compared lipid droplet (LD)-associated proteins and identified that Cox-2 was one of three major altered proteins under the FA treatment. This finding was then confirmed using immunofluorescence. Finally, Cox-2 selective inhibitor, celecoxib protected cells from PA-reduced insulin signaling Akt phosphorylation. Together, these results not only provide a dataset of protein expression change in FA treatment but also suggest that Cox-2 and lipid droplets (LDs) are potential players in PA- and OA-mediated cellular processes. PMID- 26899880 TI - Wealth differentials in the impact of conditional and unconditional cash transfers on education: findings from a community-randomised controlled trial in Zimbabwe. AB - We investigated (1) how household wealth affected the relationship between conditional cash transfers (CCT) and unconditional cash transfers (UCT) and school attendance, (2) whether CCT and UCT affected educational outcomes (repeating a year of school), (3) if baseline school attendance and transfer conditions affected how much of the transfers participants spent on education and (4) if CCT or UCT reduced child labour in recipient households. Data were analysed from a cluster-randomized controlled trial of CCT and UCT in 4043 households from 2009 to 2010. Recipient households received $18 dollars per month plus $4 per child. CCT were conditioned on above 80% school attendance, a full vaccination record and a birth certificate. In the poorest quintile, the odds ratio of above 80% school attendance at follow-up for those with below 80% school attendance at baseline was 1.06 (p = .67) for UCT vs. CCT. UCT recipients reported spending slightly more (46.1% (45.4-46.7)) of the transfer on school expenses than did CCT recipients (44.8% (44.1-45.5)). Amongst those with baseline school attendance of below 80%, there was no statistically significant difference between CCT and UCT participants in the proportion of the transfer spent on school expenses (p = .63). Amongst those with above 80% baseline school attendance, CCT participants spent 3.5% less (p = .001) on school expenses than UCT participants. UCT participants were no less likely than those in the control group to repeat a grade of school. CCT participants had .69 (.60-.79) lower odds vs. control of repeating the previous school grade. Children in CCT recipient households spent an average of .31 fewer hours in paid work than those in the control group (p < .001) and children in the UCT arm spent an average of .15 fewer hours in paid work each week than those in the control arm (p = .06). PMID- 26899882 TI - Anti-VEGF and its impact on the outer retina: retinal pigment epithelium tear after an injection of aflibercept in contralateral eye. AB - CASE REPORT: A 62-year-old woman with a history of bilateral retinal pigment epithelium detachment (PED), secondary of age-related macular degeneration (AMD), who presented with a retinal pigment epithelium (RPE) tear on her left eye after an aflibercept injection in the contralateral eye one month earlier. DISCUSSION: A RPE tear is the main complication when the anti-VEGF therapy is used for the management of the PED. Furthermore, it should be noted that systemic absorption of the drug can induce an effect on the untreated eye. PMID- 26899883 TI - Genetics of movement disorders in the next-generation sequencing era. AB - Several innovative and extremely powerful methods for sequencing nucleic acids (DNA and RNA), collectively known as next-generation sequencing technologies, have become available in the past few years. The application of these technologies is rapidly changing the landscape of both medical genetic research and clinical practice: the pace of discovery of novel disease-causing or disease predisposing genes is markedly accelerating; the phenotypic spectra associated with previously known genes is expanding; and novel tools for rapid, cheap, and comprehensive genetic testing are entering the clinical practice. As with every technological revolution, next-generation sequencing also comes with new challenges concerning the storage, the analysis, and crucially, the interpretation of the large amounts of generated data. The current possibility to sequence entire human exomes (the coding part of the genome) or entire genomes at affordable costs has brought the era of personalized medicine closer than ever, also raising new legal and ethical issues. In this article, we summarize the essential technological aspects of next-generation sequencing and discuss their applications in the field of movement disorders. We review the different strategies for gene finding enabled by these technologies (including project designs, filtering approaches, and bioinformatic tools) and we then discuss their applications in clinical practice. PMID- 26899884 TI - Enhanced performance in capacitive force sensors using carbon nanotube/polydimethylsiloxane nanocomposites with high dielectric properties. AB - Force sensors have attracted tremendous attention owing to their applications in various fields such as touch screens, robots, smart scales, and wearable devices. The force sensors reported so far have been mainly focused on high sensitivity based on delicate microstructured materials, resulting in low reproducibility and high fabrication cost that are limitations for wide applications. As an alternative, we demonstrate a novel capacitive-type force sensor with enhanced performance owing to the increased dielectric properties of elastomers and simple sensor structure. We rationally design dielectric elastomers based on alkylamine modified-multi-walled carbon nanotube (MWCNT)/polydimethylsiloxane (PDMS) composites, which have a higher dielectric constant than pure PDMS. The alkylamine-MWCNTs show excellent dispersion in a PDMS matrix, thus leading to enhanced and reliable dielectric properties of the composites. A force sensor array fabricated with alkylamine-MWCNT/PDMS composites presents an enhanced response due to the higher dielectric constant of the composites than that of pure PDMS. This study is the first to report enhanced performance of capacitive force sensors by modulating the dielectric properties of elastomers. We believe that the disclosed strategy to improve the sensor performance by increasing the dielectric properties of elastomers has great potential in the development of capacitive force sensor arrays that respond to various input forces. PMID- 26899879 TI - Diet and adipose tissue distributions: The Multi-Ethnic Study of Atherosclerosis. AB - BACKGROUND AND AIMS: Dietary quality affects cardiometabolic risk, yet its pathways of influence on regional adipose tissue depots involved in metabolic and diabetes risk are not well established. We aimed to investigate the relationship between dietary quality and regional adiposity. METHODS AND RESULTS: We investigated 5079 individuals in the Multi-Ethnic Study of Atherosclerosis (MESA) who had food-frequency questionnaires and measurement of pericardial fat and hepatic attenuation at the baseline study visit in MESA, as well as a subgroup with imaging for visceral and subcutaneous fat (N = 1390). A dietary quality score (DietQuality) was constructed to include established food group constituents of a Mediterranean-type diet. Linear models estimated associations of dietary score as well as its constituents with regional adiposity. Baseline mean age was 61 (+/- 10) years, and approximately half of the participants (47%) were male. Those with a higher DietQuality score were generally older, female, with a lower body mass index, C-reactive protein, and markers of insulin resistance. After adjustment, a higher DietQuality score was associated with lower visceral fat (lowest vs. highest dietary score quartile: 523.6 vs. 460.5 cm(2)/m; P < 0.01 for trend), pericardial fat (47.5 vs. 41.3 cm(3)/m; P < 0.01 for trend), lesser hepatic steatosis (by hepatic attenuation; 58.6 vs. 60.7 Hounsfield units; P < 0.01 for trend), but not subcutaneous fat (P = 0.39). Greater fruits, vegetables, whole grains, seeds/nuts and yogurt intake were associated with decreased adiposity, while red/processed meats were associated with greater regional adiposity. CONCLUSION: A higher quality diet pattern is associated with less regional adiposity, suggesting a potential mechanism of beneficial dietary effects on diabetes, metabolic, and cardiovascular risk. PMID- 26899885 TI - Averting the legacy of kidney disease: focus on childhood. PMID- 26899886 TI - On the relative utility of specialist-specialists and generalist-specialists. PMID- 26899887 TI - Autoimmune encephalitis. AB - Over the past decade, the clinical spectrum of autoimmune encephalitis has expanded with the emergence of several new clinicopathological entities. In particular, autoimmune encephalitis has recently been described in association with antibodies to surface receptors and ion channels on neurological tissues. Greater clinician awareness has resulted in autoimmune encephalitis being increasingly recognised in patients with unexplained neurological and psychiatric symptoms and signs. The clinical spectrum of presentations, as well as our understanding of disease mechanisms and treatment regimens, is rapidly developing. An understanding of these conditions is important to all subspecialties of Internal Medicine, including neurology and clinical immunology, psychiatry, intensive care and rehabilitation medicine. This review provides a contemporary overview of the aetiology, investigations and treatment of the most recently described autoimmune encephalitides. PMID- 26899888 TI - A tertiary hospital audit of the use of medical imaging in the 24 h preceding death. AB - This study aims to investigate the number, modality and indication for imaging studies performed on acute hospital inpatients in the 24 h prior to death. Data were obtained from retrospective analysis of deceased patients from a university affiliated tertiary hospital over a 2-year period and it was found that around one in five inpatients received medical imaging in the last 24 h of their life (364 of 1855, 19.6%). PMID- 26899889 TI - Point prevalence of general ward patients fulfilling criteria for systemic inflammatory response syndrome. AB - The systemic inflammatory response syndrome (SIRS) is defined by abnormal temperature, heart rate, minute ventilation or white cell count and can be due to infectious or non-infectious causes. In a single day, 23% of hospital ward patients fulfilled SIRS criteria. Patients with SIRS were more likely to be under medical than surgical units. One-third of the patients had evidence of infection. There was no association between SIRS criteria and increased mortality or hospital length of stay. PMID- 26899890 TI - Radiation dose difference between state of the art myocardial perfusion scintigraphy and computed tomography coronary angiography in patients undergoing evaluation for suspected coronary artery disease. AB - Minimisation of radiation exposure with cardiac imaging reduces the potential of secondary side effects. Radiation exposure from myocardial perfusion scintigraphy and computed tomography coronary angiography (CTCA) was compared. Overall doses were low with both modalities. Doses were lower in the CTCA group, but by only a small difference of 1.1 mSv. Radiation exposure should not be the primary consideration when choosing between these two modalities. PMID- 26899891 TI - What's new in osteoarthritis pathogenesis? AB - Osteoarthritis is the leading musculoskeletal cause of disability in the Western society. Despite this, it is still difficult to gain a precise definition of what osteoarthritis actually is. The methods used for the study are narrative review and viewpoint focussing on the knee. It is well known that there is a modest correlation between X-ray changes and pain. Improvements in imaging have shown that osteoarthritis should be regarded as an umbrella term for a number of pathophysiological processes leading to pain and/or cartilage loss. If these are inside the joint (such as bone marrow lesions, cartilage defects or meniscal tear) then they can be considered osteoarthritis, while those outside the joint (such as obesity, weak muscles and vitamin D deficiency) could be considered the osteoarthritis syndrome. These improvements in basic science are leading to lesion-specific therapies indicating the importance of trying to pinpoint causes of pain in the individual. PMID- 26899892 TI - An unusual case of amyloidosis leading to death. PMID- 26899893 TI - Disseminated visceral varicella zoster virus presenting with the constellation of colonic pseudo-obstruction, acalculous cholecystitis and syndrome of inappropriate ADH secretion. PMID- 26899894 TI - Screening coagulation tests are underutilised in patients on dabigatran presenting with thromboembolic or haemorrhagic events. PMID- 26899896 TI - Erratum. PMID- 26899895 TI - First, do no harm, second, do some good, third, give choice and fourth, save cash: the 1, 2, 3 and 4 of transdermal oestradiol as androgen deprivation therapy ticks all the boxes. PMID- 26899897 TI - Efficacy of antibiotic treatment and test-based culling strategies for eradicating brucellosis in commercial swine herds. AB - Swine brucellosis caused by Brucella suis biovar 2 is an emerging disease in continental Europe. Without effective vaccines being available, the European Food Safety Authority (EFSA) recommends the full depopulation of infected herds as the only strategy to eradicate B. suis outbreaks. Using data collected from 8 herds suffering natural swine brucellosis outbreaks, we assessed the efficacy of four control strategies: (i) oxytetracycline treatment only, as a default scenario, (ii) oxytetracycline treatment combined with skin testing and removal of positive animals, (iii) oxytetracycline treatment combined with serological testing (Rose Bengal test-RBT-and indirect ELISA -iELISA-) and removal of seropositive animals and (iv) oxytetracycline treatment combined with both serological (RBT/iELISA) and skin testing and removal of positive animals. A Susceptible-Infectious Removal model was used to estimate the reproduction ratio (R) for each strategy. According to this model, the oxytetracycline treatment alone was not effective enough to eradicate the infection. However, this antibiotic treatment combined with diagnostic testing at 4-monthly intervals plus immediate removal of positive animals showed to be effective to eradicate brucellosis independent of the diagnostic test strategy used in an acceptable time interval (1-2 years), depending on the initial number of infected animals. PMID- 26899898 TI - Phacoaspiration with a Cionni ring versus pars plana lensectomy, vitrectomy and sutureless transscleral IOL fixation in pediatric patients with a subluxated lens. AB - PURPOSE: To compare outcomes of phacoaspiration (PA) with Cionni ring-assisted posterior-chamber intraocular lens implantation (PCIOL) versus pars plana lensectomy (PPL) with anterior vitrectomy (AV) and sutureless transscleral fixation of the IOL (TSFIOL) assisted with fibrin glue in the management of a subluxated lens. METHODS: In this prospective and comparative interventional study, one eye of children with a bilateral subluxated lens was randomized to undergo PA with PCIOL using a Cionni ring (group A: n = 14 eyes), and the other eye underwent PPL + AV with glue-assisted TSFIOL (group B: n = 14 eyes). The outcome measures included best-corrected visual acuity (BCVA) in logMAR units and rates of complications at 12-month follow-up visits. RESULTS: 28 eyes of 14 children (age: 8.06 +/- 4.49 years) were included in the study. BCVA improved from preoperative value of 1.21 to 0.4 (p = 0.001) in group A and from 1.53 to 0.31 (p = 0.001) in group B at month 12. There was no significant difference in the BCVA on comparing the two groups at month 12 (p > 0.411). Postoperative complications in group A included corneal edema (two eyes), Cionni hook capture (one eye), elevated IOP (one eye), and posterior capsular opacification (five eyes). In group B, corneal edema was seen in two eyes, hypotony in one eye, vitreous hemorrhage in one eye and pupillary optic capture in four eyes. CONCLUSION: Head-to-head comparison of the two techniques demonstrates no significant difference in the rates of complications at month 12. The decision to choose either technique may be based on the operating surgeon's skill, experience and preference. PMID- 26899899 TI - Development and testing of an automated computer tablet-based method for self testing of high and low contrast near visual acuity in ophthalmic patients. AB - PURPOSE: Many eye diseases require on-going assessment for optimal management, creating an ever-increasing burden on patients and hospitals that could potentially be reduced through home vision monitoring. However, there is limited evidence for the utility of current applications and devices for this. To address this, we present a new automated, computer tablet-based method for self-testing near visual acuity (VA) for both high and low contrast targets. We report on its reliability and agreement with gold standard measures. METHODS: The Mobile Assessment of Vision by intERactIve Computer (MAVERIC) system consists of a calibrated computer tablet housed in a bespoke viewing chamber. Purpose-built software automatically elicits touch-screen responses from subjects to measure their near VA for either low or high contrast acuity. Near high contrast acuity was measured using both the MAVERIC system and a near Landolt C chart in one eye for 81 patients and low contrast acuity using the MAVERIC system and a 25 % contrast near EDTRS chart in one eye of a separate 95 patients. The MAVERIC near acuity was also retested after 20 min to evaluate repeatability. RESULTS: Repeatability of both high and low contrast MAVERIC acuity measures, and their agreement with the chart tests, was assessed using the Bland-Altman comparison method. One hundred and seventy-three patients (96 %) completed the self- testing MAVERIC system without formal assistance. The resulting MAVERIC vision demonstrated good repeatability and good agreement with the gold-standard near chart measures. CONCLUSIONS: This study demonstrates the potential utility of the MAVERIC system for patients with ophthalmic disease to self-test their high and low contrast VA. The technique has a high degree of reliability and agreement with gold standard chart based measurements. PMID- 26899901 TI - Echinocandins for antifungal prophylaxis in liver transplant recipients: Advance in the field or variation on a theme? PMID- 26899900 TI - A retrospective cohort study in patients with tractional diseases of the vitreomacular interface (ReCoVit). AB - PURPOSE: To assess how vitreomacular adhesion (VMA), vitreomacular traction (VMT), and macular holes (MH) evolve, and to assess visual acuity outcomes associated with different management strategies for each subgroup. METHODS: Retrospective, single-center, observational study of 400 patients (556 eyes) who presented with optical coherence tomography (OCT) findings related to tractional diseases of the vitreomacular interface (187 with bilateral disease). The outcomes measured include prevalence of symptoms, rates of disease stabilization, spontaneous resolution, and disease progression necessitating surgical intervention. Size of VMA/VMT was not measured. RESULTS: Vision loss and metamorphopsia were the leading causes for referral. Patients were followed for a mean of 10.9 months (median 6.9 months). Spontaneous resolution occurred in 22.7 % (46/203) of eyes with VMT and in 7.3 % (9/124) of eyes with VMA (P < .001). In the former group, 34.1 % (14 eyes) showed improved visual acuity (P = .001). During follow-up, 11.3 % (14/124) of eyes with VMA showed disease progression; six (4.8 %) developed a macular hole. Eleven of the 203 eyes with VMT (5.4 %) developed a macular hole; 52 of 203 eyes with VMT (25.6 %) had disease progression that resulted in patients opting for pars plana vitrectomy (PPV). Of the eyes with VMA, 4.8 % (6/124) had disease progression resulting in patients opting for PPV. CONCLUSIONS: Better visual acuity outcomes were found in eyes with spontaneous resolution compared to the other groups. Spontaneous resolution of VMT and VMA was rare, whereas disease progression resulting in PPV was more common. PMID- 26899902 TI - [Hospital readmission after postpartum discharge of term newborns in two maternity wards in Stockholm and Marseille]. AB - The consequences of early postpartum discharge (EPPD, within 2 days after birth) on newborn health remain debated. Early discharge has been associated with increased neonatal morbidity. However, neonatal re-hospitalization can be prevented by careful follow-up during the 1st week after birth. We compared the early neonatal hospitalization of term newborns over 2 years in two hospitals: Karolinska University Hospital in Stockholm (n=7300 births), which allowed early discharge from 6h after birth with specific neonatal follow-up, and Marseille University Hospital (AP-HM) (n=4385) where postpartum discharge was more conventional after 72 h. During the study period, the EPPD rate was 41% vs. 2% in Stockholm and Marseille, respectively (P<0.001). Hospital readmission was comparable (5.60/00 vs. 70/00, P=0.2). The leading cause associated with hospitalization was icterus in Stockholm (76% vs. 26%, P<0.001) and feeding difficulties in Marseille (17% vs. 48%, P<0.001). In conclusion, close neonatal follow-up during the 1st week of life associated with restricted maternal and neonatal eligibility criteria for EPPD are required to prevent early neonatal re hospitalization. PMID- 26899903 TI - Confirmed severe maternal morbidity is associated with high rate of preterm delivery. AB - BACKGROUND: Because severe maternal morbidity (SMM) is increasing in the United States, affecting up to 50,000 women per year, there was a recent call to review all mothers with SMM to better understand their morbidity and improve outcomes. Administrative screening methods for SMM have recently been shown to have low positive predictive value for true SMM after chart review. To ultimately reduce maternal morbidity and mortality we must better understand risk factors, and preventability issues about true SMM such that interventions could be designed to improve care. OBJECTIVE: Our objective was to determine risk factors associated with true SMM identified from California delivery admissions, including the relationship between SMM and preterm delivery. STUDY DESIGN: In this retrospective cohort study, SMM cases were screened for using International Classification of Diseases, Ninth Revision codes for severe illness and procedures, prolonged postpartum length of stay, intensive care unit admission, and transfusion from all deliveries in 16 hospitals from July 2012 through June 2013. Charts of screen-positive cases were reviewed and true SMM diagnosed based on expert panel agreement. Underlying disease diagnosis was determined. Women with true-positive SMM were compared to SMM-negative women for the following variables: maternal age, ethnicity, gestational age at delivery, prior cesarean delivery, and multiple gestation. RESULTS: In all, 491 women had true SMM and 66,977 women did not have SMM for a 0.7% rate of true SMM. Compared to SMM negative women, SMM cases were significantly more likely to be age >35 years (33.6 vs 23.8%; P < .0001), be African American (14.1 vs 7.9%; P < .0001), have had a multiple gestation (9.7 vs 2.1%; P < .0001), and, for the multiparous women, have had a prior cesarean delivery (58 vs 30.2%; P < .0001). Preterm delivery was significantly more common in SMM women compared to SMM-negative women (41 vs 8%; P < .0001), including delivery <32 weeks (18 vs 2%; P < .0001). The most common underlying disease was obstetric hemorrhage (42%) followed by hypertensive disorders (20%) and placental hemorrhage (14%). Only 1.6% of women with SMM had cardiovascular disease as the underlying disease category. CONCLUSION: An extremely high proportion of women with severe morbidity (42.5%) delivered preterm with 17.8% delivering <32 weeks, which underscores the importance of access to appropriate-level care for mothers with SMM and their newborns. Further, the extremely high rate of preterm delivery (75%) in women with placental hemorrhage in combination with their 63% prior cesarean delivery rate highlights another risk of prior cesarean delivery: subsequent preterm delivery. These data provide a reminder that a cesarean delivery could be a contributing factor to not only hemorrhage-related SMM, but also to increased subsequent preterm delivery, more reason to continue national efforts to safely reduce initial cesarean deliveries. PMID- 26899904 TI - Assessment of a cervicometer compared to transvaginal ultrasound in identifying women with a short cervical length: a multicenter study. AB - BACKGROUND: Preterm birth remains a major cause of neonatal morbidity and mortality worldwide. Short cervical length (CL) as measured by transvaginal ultrasound (TVU) in the second trimester represents the single most predictive risk factor for spontaneous preterm birth. Previous studies have addressed, in part, the limitations of TVU availability by utilizing a cervicometer to screen patients for short cervix, identifying those patients who may not benefit from TVU CL screening. In view of the prior studies indicating that a cervicometer measurement may have a high negative predictive value (NPV) for a sonographically short cervix, we sought to identify the ideal cervicometer threshold value in a prospective, multicenter study. OBJECTIVE: The primary objective was to determine the cervicometer CL measurement threshold that provides a high NPV for the identification of patients who are highly unlikely to have a TVU CL measurement <=20 and <=25 mm and, therefore, may forego TVU. STUDY DESIGN: This prospective study, executed in 5 US centers, included 401 women >=18 years of age who provided written informed consent to undergo CL measurement in the mid trimester. All women underwent both cervicometer- and TVU-measured CLs by individuals blinded to results of the other measurement. Both measurements were performed at 17-23 weeks' gestation (visit 1) and repeated at 24-29 weeks' gestation (visit 2). All TVU measurement images were reviewed by a central reader. Test characteristics and receiver operating characteristic curves were created to determine and confirm the optimal cervicometer CL threshold, maximizing the NPV. RESULTS: In all, 358 subjects were evaluable at visit 1 and 267 at visit 2. At visit 1, the average TVU CL was 38.7 +/- 7.6 mm and the average cervicometer CL was 30.3 +/- 8.8 mm. Similar measurements were seen at visit 2. Receiver operating characteristic curves were utilized to graphically identify a cervicometer CL threshold of 30 mm that maximized sensitivity while minimizing the false-positive rate. The 30-mm cervicometer CL threshold provided a 98-100% NPV and 0.0 negative likelihood ratio for identification of women who have a low likelihood to have a sonographic short cervix (ie, transvaginal CL <=20 mm or <=25 mm). The 17-23 weeks' gestation 30-mm cervicometer CL threshold has 100% sensitivity, 45-46% specificity, and 1.8 and 0.0 positive and negative likelihood ratios to predict sonographic CL <=20 and <=25 mm. CONCLUSION: Cervicometer CL screening successfully identifies women at low risk for short transvaginal CL. Use of a 30-mm threshold by cervicometer CL measurement confers a 98-100% NPV, with high sensitivity and moderate specificity to predict a TVU short CL. Cervicometer measurement of CL may permit almost 50% of women to avoid TVU. PMID- 26899905 TI - Temporal trends in obstetric trauma and inpatient surgery for pelvic organ prolapse: an age-period-cohort analysis. AB - BACKGROUND: The rates of cesarean delivery have increased over time in industrialized countries, while the rates of instrumental vaginal delivery have declined. Instrumental vaginal delivery and obstetric trauma are risk factors for pelvic floor disorders. OBJECTIVE: We carried out a population-based study to quantify the association between temporal changes in obstetric trauma during childbirth and temporal changes in surgery for pelvic organ prolapse. STUDY DESIGN: We designed a retrospective analysis to examine age-specific trends in vaginal and cesarean delivery, obstetric trauma, and surgery for pelvic organ prolapse among all women (pregnant and nonpregnant) in Washington State, from 1987 through 2009. Cases of obstetric trauma (including severe perineal tears and high vaginal lacerations) and inpatient surgery for pelvic organ prolapse were identified among all hospitalizations. Temporal trends and age-period-cohort regression analyses were used to quantify the time period, age, and birth cohort effects among women born from 1920 through 1980. RESULTS: From 1987 through 2009, cesarean delivery rates among women aged 15-44 years increased from 12.7-18.1 per 1000 women, vaginal delivery rates remained stable, and instrumental vaginal delivery rates declined from 6.3-3.9 per 1000 women. Obstetric trauma decreased from 6.7 in 1987 to 2.5 per 1000 women aged 15-44 years in 2009. Surgery for pelvic organ prolapse decreased from 2.1 in 1987 to 1.4 per 1000 women aged 20-84 years in 2009. Obstetric trauma rates in 1987 through 1999 among women 15-44 years old were strongly correlated with the rates of surgery for pelvic organ prolapse among women 25-54 years of age 10 years later in 1997 through 2009 (correlation coefficient 0.87, P < .001). Similarly, rates of midpelvic forceps delivery in 1987 through 1999 were correlated with the rates of surgery for pelvic organ prolapse 10 years later (correlation coefficient 0.72, P < .01). Regression analyses showed a strong effect of age on surgery for prolapse, temporal decline in surgery, and an effect of birth cohort, as younger cohorts (women born in >=1965 vs 1940) had lower rates of surgery for pelvic organ prolapse. CONCLUSION: Temporal decline in instrumental vaginal delivery and obstetric trauma may have contributed to the reduction in surgery for pelvic organ prolapse. PMID- 26899906 TI - Clinical validation of a noninvasive prenatal test for genomewide detection of fetal copy number variants. AB - BACKGROUND: Current cell-free DNA assessment of fetal chromosomes does not analyze and report on all chromosomes. Hence, a significant proportion of fetal chromosomal abnormalities are not detectable by current noninvasive methods. Here we report the clinical validation of a novel noninvasive prenatal test (NIPT) designed to detect genomewide gains and losses of chromosomal material >=7 Mb and losses associated with specific deletions <7 Mb. OBJECTIVE: The objective of this study is to provide a clinical validation of the sensitivity and specificity of a novel NIPT for detection of genomewide abnormalities. STUDY DESIGN: This retrospective, blinded study included maternal plasma collected from 1222 study subjects with pregnancies at increased risk for fetal chromosomal abnormalities that were assessed for trisomy 21 (T21), trisomy 18 (T18), trisomy 13 (T13), sex chromosome aneuploidies (SCAs), fetal sex, genomewide copy number variants (CNVs) >=7 Mb, and select deletions <7 Mb. Performance was assessed by comparing test results with findings from G-band karyotyping, microarray data, or high coverage sequencing. RESULTS: Clinical sensitivity within this study was determined to be 100% for T21 (95% confidence interval [CI], 94.6-100%), T18 (95% CI, 84.4-100%), T13 (95% CI, 74.7-100%), and SCAs (95% CI, 84-100%), and 97.7% for genomewide CNVs (95% CI, 86.2-99.9%). Clinical specificity within this study was determined to be 100% for T21 (95% CI, 99.6-100%), T18 (95% CI, 99.6-100%), and T13 (95% CI, 99.6-100%), and 99.9% for SCAs and CNVs (95% CI, 99.4-100% for both). Fetal sex classification had an accuracy of 99.6% (95% CI, 98.9-99.8%). CONCLUSION: This study has demonstrated that genomewide NIPT for fetal chromosomal abnormalities can provide high resolution, sensitive, and specific detection of a wide range of subchromosomal and whole chromosomal abnormalities that were previously only detectable by invasive karyotype analysis. In some instances, this NIPT also provided additional clarification about the origin of genetic material that had not been identified by invasive karyotype analysis. PMID- 26899907 TI - A human papillomavirus vaccination program for low-income postpartum women. AB - BACKGROUND: Effective interventions are needed to address the low rate of human papillomavirus (HPV) vaccination in the United States, particularly among girls and women 16-26 years old. Counseling and offering the vaccine to postpartum patients could be an effective strategy to increase uptake among young women who did not complete the 3-dose series at an earlier age. OBJECTIVE: The purpose of this evaluation was to assess the effectiveness of a multicomponent program designed for postpartum women that used patient navigators (PNs) and reminders for follow-up visits to improve uptake and completion of the HPV vaccine series. STUDY DESIGN: As part of standard care, patients <=26 years of age from Galveston County, Texas, who delivered an infant from November 2012 through June 2014 at a public hospital were counseled and offered the HPV vaccine postpartum. PNs assisted with scheduling follow-up injections during postpartum or well-child visits. A program evaluation was conducted after 20 months. RESULTS: Of 1038 patients approached, only 161 (15.5%) had previously completed the vaccine series. Of the 877 patients who had not completed the series, 661 (75.4%) received at least 1 dose postpartum, with 575 patients receiving their first dose and 86 receiving their second or third doses. By April 2015, initiation rates had increased as a result of this program from 25.4% before the program was initiated to 80.8% and completion rates from 15.5-65.1%. Missed appointments for injections were less likely among those who received text message reminders and more likely among those with >=2 prior pregnancies. Those who were Hispanic or had received an influenza vaccination in the last year were more likely to initiate and complete the series through this program. Patients who missed >=1 follow-up appointments were less likely to complete the vaccine series. CONCLUSION: Offering the HPV vaccine postpartum dramatically increased initiation rates among postpartum patients. PN and text messages ensured that a high percentage completed all 3 doses. PMID- 26899908 TI - Easy sonographic differential diagnosis between intrauterine pregnancy and cesarean delivery scar pregnancy in the early first trimester. AB - BACKGROUND: Cesarean scar pregnancy (CSP) is a serious complication of pregnancy, which consists of implantation of the gestational sac in the hysterotomy scar. This condition is increasing in frequency and often poses a diagnostic challenge. Its diagnosis is dependent on visual assessment of the uterus on the longitudinal sagittal ultrasound plane. Misdiagnosing a low intrauterine chorionic sac as a CSP, or a true scar pregnancy as an intrauterine pregnancy (IUP), may lead to adverse outcomes including hysterectomy. OBJECTIVE: The objective of the study is to describe a sonographic method for the differential diagnosis of CSP vs IUP in early gestation. The current study tests the hypothesis that on a first-trimester ultrasound performed between 5-10 weeks of gestation, the relative location of the center of gestational sac to the midpoint of the uterus along a longitudinal line between the external cervical os and the fundus can be used for early detection of CSPs. STUDY DESIGN: This is a retrospective review of electronically archived ultrasound images of IUP and CSP between 5-10 weeks of gestation. A total of 242 ultrasound images were analyzed: 185 cases of normal IUPs (including 128 in anteverted uteri, 31 in retroverted uteri, and 26 IUPs with history of cesarean delivery) and 57 cases of CSPs diagnosed from 2004 through 2015 in a single institution. The following measurements were made for each case: distance from the external cervical os to the uterine fundus, the midpoint axis of the uterus, the distance from the external cervical os to the center of gestational sacs, and the distance from the external cervical os to the most distant edge of the gestational sacs from the cervix. RESULTS: The location of the center of the gestational sac relative to the midpoint axis of the uterus between 5-10 weeks of gestation differentiated between IUP and CSP (mean 17.8 vs -10.6 mm, respectively, P = .0001), indicating that most CSPs are located proximally to the midpoint axis of the uterus whereas most normal IUPs are located distally from the midpoint of the uterus. Using location of the center of the gestational sac as a marker of CSPs between 5-10 weeks of gestation yielded the following characteristics of diagnostic accuracy: sensitivity 93.0% and specificity 98.9%. The likelihood ratio of the positive test was 84.5. The likelihood ratio of the negative test was 0.07. CONCLUSION: The location of the center of the gestational sac relative to the midpoint axis of the uterus can be used as an easy method for sonographic differentiation of IUP and CSP between 5-10 weeks of gestation. PMID- 26899909 TI - The impact of acute and chronic strenuous exercise on pelvic floor muscle strength and support in nulliparous healthy women. AB - BACKGROUND: Strenuous physical activity, which is known to increase intraabdominal pressure and theoretically places stress on the pelvic floor, may affect pelvic support in nulliparous women. OBJECTIVE: The aims of this study were to: (1) examine the differences in maximal vaginal descent (MVD), vaginal resting pressure (VRP), and pelvic floor muscle strength (PFMS) between women who habitually perform strenuous exercise vs women who refrain from performing strenuous exercise; and (2) compare MVD, VRP, and PFMS before and immediately following physical activity in the strenuous and nonstrenuous groups separately. STUDY DESIGN: Participants were healthy nulliparous women ages 18-35 years who were habitual strenuous or nonstrenuous exercisers. Women in the strenuous group participated in CrossFit (CrossFit, Inc., Washington, DC) at least 3 days per week for at least 6 months. We assessed anthropometric and body composition values using standardized procedures. Participants completed the Pelvic Organ Prolapse Quantification examination and pelvic muscle strength assessment before and again within 15 minutes of completing exercise (CrossFit for the strenuous group and self-paced walking for the nonstrenuous). A research nurse masked to study group assignment recorded MVD, defined as the greatest value of anterior, posterior, or apical support, and VRP and PFMS using a perineometer. Maximal PFMS was recorded as the highest pressure measured in 3 vaginal contraction trials. Data were analyzed using parametric and nonparametric tests as appropriate. P < .05 was considered significant. RESULTS: Seventy nulliparous women participated in the study, 35 in each group. The mean age was 24.77 +/- 4.3 years. Compared to the nonstrenuous group, strenuous participants were heavier (64.70 +/- 7.78 kg vs 60.6 +/- 8.99 kg, P = .027), had lower percent body fat (23.36 +/- 5.88% vs 27.55 +/- 7.07%, P = .003), and had higher handgrip strength (20.78 +/- 5.97 kg vs 16.04 +/- 11.04 kg, P = .001). Before exercise, there were no significant differences in VRP (P = .167), MVD (P = .49), or maximal PFMS (P = .773) between the strenuous and nonstrenuous groups. Immediately following exercise, we observed significant increases in MVD in both the strenuous (P = .008) and nonstrenuous (P = .025) groups, indicating marginal decreases in support. VRP significantly decreased in both groups after exercise. Maximal PFMS did not change significantly in either group after exercise. CONCLUSION: After an exercise bout typical for each group, vaginal support and VRP decreased slightly in both groups. Based on preexercise measures, chronic strenuous exercise demonstrated neither beneficial nor deleterious effects on pelvic floor strength or support. While strenuous women had greater grip strength than nonstrenuous women, PFMS was not significantly greater, suggesting that targeted pelvic floor muscle strengthening, rather than general muscle fitness, is needed to maximize PFMS. PMID- 26899910 TI - Digital image correlation of coated and uncoated Religa Heart_Ext ventricular assist device. AB - The digital image correlation is used to estimate influence of deposited heamocompatible coatings (gold and titanium nitride) on mechanical response of ventricular assist device Religa Heart_Ext made of Bionate II (thermoplastic polycarbonate urethane) under working conditions by comparison of the coated Religa Heart_Ext with uncoated Religa Heart_Ext. The DIC is applied for experimental investigation of the strains and displacements distribution on external surface of the blood chamber of ventricular assist device during loading. The experiment was conducted in a hydraulic system with water at operating temperatures of 25 and 37 degrees C, as well as under static pressures: 80, 120, 180, 220 and 280 mmHg, and static underpressures: -25, -45, 75 mmHg. The subsequent images were taken after stabilization of pressure on a set level. The applied research method shows that the nano-coating of 30 nm in thickness significantly affects deformation of the blood chamber of Religa Heart_Ext in macro scale. The proposed composition of coatings increases strain on external surface of the ventricular assist device. PMID- 26899912 TI - Ectopic expression of a tobacco vacuolar invertase inhibitor in guard cells confers drought tolerance in Arabidopsis. AB - There are several hypotheses that explain stomatal behavior. These include the concept of osmoregulation mediated by potassium and its counterions malate and chlorine and the more recent starch-sugar hypothesis. We have previously reported that the activity of the sucrose cleavage enzyme, vacuolar invertase (VIN), is significantly higher in guard cells than in other leaf epidermal cells and its activity is correlated with stomatal aperture. Here, we examined whether VIN indeed controls stomatal movement under normal and drought conditions by transforming Arabidopsis with a tobacco vacuolar invertase inhibitor homolog (Nt inhh) under the control of an abscisic acid-sensitive and guard cell-specific promoter (AtRab18). The data obtained showed that guard cells of transgenic Arabidopsis plants had lower VIN activity, stomatal aperture and conductance than that of wild-type plants. Moreover, the transgenic plants also displayed higher drought tolerance than wild-type plants. The data indicate that VIN is a promising target for manipulating stomatal function to increase drought tolerance. PMID- 26899913 TI - Imaging and outcomes in cardiac, valvular, and peripheral arterial disease. PMID- 26899914 TI - CardioPulse: EHJ Interview with Jeroen Bax. AB - Jeroen Bax discusses training in imaging for cardiology Fellows at ESC Congress in London on EHJ Today-The voice of leaders, with Julia Stehli MD. PMID- 26899911 TI - Histone acetyltransferease p300 modulates TIM4 expression in dendritic cells. AB - TIM4 (T cell immunoglobulin mucin domain molecule-4) plays a critical role in the initiation of skewed T helper (Th) 2 polarization. The factors regulating TIM4 expression are unclear. This study tests a hypothesis that p300 and STAT6 (signal transducer and activator transcription-6) regulates TIM4 expression in dendritic cells (DC). In this study, a food allergy mouse model was developed with ovalbumin (a specific antigen) and cholera toxin (CT; an adjuvant). The chromatin immunoprecipitation assay was performed to evaluate the chromatin changes at TIM4 and STAT6 promoters. The TIM4 expression was evaluated by real time RT-PCR and Western blotting. The results showed that high levels of p300 and TIM4 were detected in the intestinal DCs of mice with intestinal allergy. p300 is involved in the CT-induced TIM4 expression in DCs. p300 interacts with the chromatin at the TIM4 promoter locus in DCs isolated from allergic mice. CT increases p300 expression to regulate STAT6 levels in DCs. STAT6 mediates the CT-induced TIM4 expression in DCs. In conclusion, p300 and STAT6 mediate the microbial product CT induced TIM4 expression in DCs. PMID- 26899915 TI - Blood collection, components preparation and distribution in Iran, 2008-2012. AB - BACKGROUND: The information about the dynamics of blood collection, components preparation and distribution in Iran was measured and compared during 2008-2012. STUDY DESIGNS AND METHODS: The survey instruments were based on collecting data from all 220 blood collections and blood processing centers over the country, registering them in the validated data base and reporting them to headquarter of Iranian Blood Transfusion Organization. RESULTS: Total blood collection increased during this period, and in 2012 represented a 12.6 percent increase compared to that in 2008. On average, red blood cells, fresh frozen plasma and platelet concentrate were prepared from 95.5 +/- 2.4, 81 +/- 3.8 and 47 +/- 8.8 percent of all whole blood collection. From 2008 to 2011, the distribution of whole blood and fresh frozen plasma revealed different patterns. For whole blood, declines were noted, while for fresh frozen plasma increases were reported. In addition the distribution of red blood cells and platelet concentrate did not change considerably. Also between 2008 and 2012, the mean percentage of outdated and discarded units was 3.6 +/- 1 and 5.2 +/- 4.6. CONCLUSION: This study as a first national survey provides comprehensive information about the blood supply, components preparation and distribution, and helps to define strategy for the future. PMID- 26899916 TI - Hematopoietic cell transplantation activity of Turkey in 2014: Ongoing increase in HCT rates. AB - Hematopoietic cell transplantation is an established treatment option with curative potential for a variety of clinical conditions. The last decade especially witnessed a remarkable increase in HCT activity in Turkey. In 2014, 696 pediatric and 2631 adult (total 3327) HCT were performed in Turkey. Corresponding transplant rates per 10 million inhabitants for autologous-HCT and allogeneic-HCT were 226 and 202, respectively. Total HCT procedures in Turkey increased 177% in the last 5 years and 791% in the last 14 years. This report focuses mainly on HCT activity of Turkey in 2014 based on the national HCT registry and presents a general picture of national HCT activity. PMID- 26899917 TI - Low serum vitamin D levels are associated with shorter survival after first-line azacitidine treatment in patients with myelodysplastic syndrome and secondary oligoblastic acute myeloid leukemia. AB - BACKGROUND & AIMS: Azacitidine (AZA) therapy has become the recommended first line treatment for patients with high-risk myelodysplastic syndromes (MDS) and oligoblastic (<30% bone marrow blasts) acute myeloid leukemia (AML). However, improvement of the efficacy of AZA treatment remains a challenge. We retrospectively tested the hypothesis that VitD levels (25-hydroxyvitamin D3) prior to start of first-line AZA therapy are predictive of overall survival (OS) in patients diagnosed with MDS and secondary oligoblastic AML. Furthermore, the antiproliferative effects of AZA in combination with 25-hydroxyvitamin D3 and 1alpha,25-dihydroxyvitamin D3 were investigated in vitro. METHODS: A total of 58 patients treated at our center between 2006 and 2014 were analyzed. Serum levels of VitD were quantified using a standard, commercially available 25 hydroxyvitamin D3 chemiluminescent immunoassay. Effects on cell proliferation were assessed using tetrazolium-based MTT assays. RESULTS: Median serum VitD level prior to AZA treatment was 32.8 nM (range 11.0-101.5 nM). Patient, disease and treatment characteristics did not differ significantly between the low (<=32.8 nM; n = 29) and high (>32.8 nM; n = 29) VitD group. Estimated probability of 2-year OS in the low versus high VitD group was 14% versus 40% (P < 0.05). In multivariable analysis with OS as endpoint, adverse cytogenetics (HR 2.66, P = 0.03) and VitD (per 10 nM decrease, HR 1.68, P = 0.02) were independent predictors of worse survival. In-vitro treatment of myeloid cell lines with AZA in combination with VitD produced synergistic and additive antiproliferative effects. Addition of nanomolar VitD concentrations to AZA resulted in potentiation of AZA activity. Conversely, combination with the VitD antagonist TEI-9647 resulted in inhibition of AZA activity. CONCLUSIONS: Our study suggests that higher VitD levels were associated with a survival advantage following first line AZA therapy. Enhanced cytotoxic effects upon combination treatment may contribute to the observed clinical effects. VitD repletion/supplementation during AZA treatment should be explored. PMID- 26899919 TI - MxMn8O16 (M = Ag or K) as promising cathode materials for secondary Mg based batteries: the role of the cation M. AB - AgxMn8O16 (Ag-OMS-2) and KxMn8O16 (K-OMS-2) were investigated as high voltage cathode materials for Mg based batteries. Both MxMn8O16 materials delivered high initial capacities (>180 mA h g(-1)), and KxMn8O16 showed high cycle stability with a reversible capacity of >170 mA h g(-1) after 20 cycles. PMID- 26899921 TI - Danish Ophthalmology - from start to 1865. AB - This short paper mentioned the medical treatment using the 'holy' springs, the first 'eye doctor' in Denmark, the first picture of spectacles which was found in Viborg Cathedral of the high priest before he performs circumcisio praeputii on Jesus Christ, further cataract reclination in Denmark from around year zero and cataract extraction in 1667 in Denmark on a goose by Francisco Borri and on humans by the Danish Georg Heuermann in 1755. Epidemic military eye diseases in 1807, 1856 and 1865 are also described in this study. From 1856, a new ophthalmological period started in Denmark with the first eye hospital (lazaret only for eye diseases), and in 1864, patients with eye diseases were transported from the few beds in the surgical departments in the municipal hospital to the first civil eye department in Denmark, the eye hospital Sct. Annae in Copenhagen. The new scientific period started with Jacob Christian Bentz (ophthalmia granulosa, joint editor of the Danish Medical Journal) and Heinrich Lehmann. PMID- 26899918 TI - A historical study of appendicular fractures in veterans with traumatic chronic spinal cord injury: 2002-2007. AB - OBJECTIVE: Describe the incidence and distribution of appendicular fractures in a cohort of veterans with spinal cord injury (SCI). DESIGN: Retrospective, observational study of fractures in veterans with a chronic traumatic SCI. SETTING: The Veterans Health Administration (VA) healthcare system. PARTICIPANTS: Veterans included in the VA Spinal Cord Dysfunction Registry from Fiscal Years (FY) FY2002-FY2007. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Description of fractures by site and number. Mortality at one year following incident fracture among men with single vs. multiple fractures. RESULTS: Male and female veterans sustained incident fractures with similar observed frequency (10.5% vs 11.5%). The majority of fractures occurred in the lower extremities for both men and women. In men, a complete extent of injury (compared to incomplete) was associated with 41% greater relative risk (RR) of incident fracture (RR 1.41, 95% confidence interval [1.17, 1.70]) among those with tetraplegia, but not paraplegia. Furthermore, many men (33.9%, n = 434) sustained multiple fractures over the course of the study. There were no differences in mortality between men who sustained a single fracture and those who had multiple fractures. CONCLUSIONS: The extent of injury may be an important predictor of fracture risk for male veterans with tetraplegia. Once a fracture occurs, male veterans with SCI appear to be at high risk for additional fractures. PMID- 26899922 TI - Reduced mate availability leads to evolution of self-fertilization and purging of inbreeding depression in a hermaphrodite. AB - Basic models of mating-system evolution predict that hermaphroditic organisms should mostly either cross-fertilize, or self-fertilize, due to self-reinforcing coevolution of inbreeding depression and outcrossing rates. However transitions between mating systems occur. A plausible scenario for such transitions assumes that a decrease in pollinator or mate availability temporarily constrains outcrossing populations to self-fertilize as a reproductive assurance strategy. This should trigger a purge of inbreeding depression, which in turn encourages individuals to self-fertilize more often and finally to reduce male allocation. We tested the predictions of this scenario using the freshwater snail Physa acuta, a self-compatible hermaphrodite that preferentially outcrosses and exhibits high inbreeding depression in natural populations. From an outbred population, we built two types of experimental evolution lines, controls (outcrossing every generation) and constrained lines (in which mates were often unavailable, forcing individuals to self-fertilize). After ca. 20 generations, individuals from constrained lines initiated self-fertilization earlier in life and had purged most of their inbreeding depression compared to controls. However, their male allocation remained unchanged. Our study suggests that the mating system can rapidly evolve as a response to reduced mating opportunities, supporting the reproductive assurance scenario of transitions from outcrossing to selfing. PMID- 26899923 TI - A polyphasic taxonomic approach in isolated strains of Cyanobacteria from thermal springs of Greece. AB - Strains of Cyanobacteria isolated from mats of 9 thermal springs of Greece have been studied for their taxonomic evaluation. A polyphasic taxonomic approach was employed which included: morphological observations by light microscopy and scanning electron microscopy, maximum parsimony, maximum likelihood and Bayesian analysis of 16S rDNA sequences, secondary structural comparisons of 16S-23S rRNA Internal Transcribed Spacer sequences, and finally environmental data. The 17 cyanobacterial isolates formed a diverse group that contained filamentous, coccoid and heterocytous strains. These included representatives of the polyphyletic genera of Synechococcus and Phormidium, and the orders Oscillatoriales, Spirulinales, Chroococcales and Nostocales. After analysis, at least 6 new taxa at the genus level provide new evidence in the taxonomy of Cyanobacteria and highlight the abundant diversity of thermal spring environments with many potential endemic species or ecotypes. PMID- 26899924 TI - Impact of sustainable feeds on omega-3 long-chain fatty acid levels in farmed Atlantic salmon, 2006-2015. AB - As the global population and its demand for seafood increases more of our fish will come from aquaculture. Farmed Atlantic salmon are a global commodity and, as an oily fish, contain a rich source of the health promoting long-chain omega-3 fatty acids, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. Replacing the traditional finite marine ingredients, fishmeal and fish oil, in farmed salmon diets with sustainable alternatives of terrestrial origin, devoid of EPA and DHA, presents a significant challenge for the aquaculture industry. By comparing the fatty acid composition of over 3,000 Scottish Atlantic salmon farmed between 2006 and 2015, we find that terrestrial fatty acids have significantly increased alongside a decrease in EPA and DHA levels. Consequently, the nutritional value of the final product is compromised requiring double portion sizes, as compared to 2006, in order to satisfy recommended EPA + DHA intake levels endorsed by health advisory organisations. Nevertheless, farmed Scottish salmon still delivers more EPA + DHA than most other fish species and all terrestrial livestock. Our findings highlight the global shortfall of EPA and DHA and the implications this has for the human consumer and examines the potential of microalgae and genetically modified crops as future sources of these important fatty acids. PMID- 26899925 TI - Comparison of pectin-degrading fungal communities in temperate forests using glycosyl hydrolase family 28 pectinase primers targeting Ascomycete fungi. AB - Fungi have developed a wide assortment of enzymes to break down pectin, a prevalent polymer in plant cell walls that is important in plant defense and structure. One enzyme family used to degrade pectin is the glycosyl hydrolase family 28 (GH28). In this study we developed primers for the amplification of GH28 coding genes from a database of 293 GH28 sequences from 40 fungal genomes. The primers were used to successfully amplify GH28 pectinases from all Ascomycota cultures tested, but only three out of seven Basidiomycota cultures. In addition, we further tested the primers in PCRs on metagenomic DNA extracted from senesced tree leaves from different forest ecosystems, followed by cloning and sequencing. Taxonomic specificity for Ascomycota GH28 genes was tested by comparing GH28 composition in leaves to internal transcribed spacer (ITS) amplicon composition using pyrosequencing. All sequences obtained from GH28 primers were classified as Ascomycota; in contrast, ITS sequences indicated that fungal communities were up to 39% Basidiomycetes. Analysis of leaf samples indicated that both forest stand and ecosystem type were important in structuring fungal communities. However, site played the prominent role in explaining GH28 composition, whereas ecosystem type was more important for ITS composition, indicating possible genetic drift between populations of fungi. Overall, these primers will have utility in understanding relationships between fungal community composition and ecosystem processes, as well as detection of potentially pathogenic Ascomycetes. PMID- 26899930 TI - In search of non-conventional surface oxidic motifs of Cu on Au(111). AB - Growing ultrathin oxide layers on metal surfaces presents a new class of low dimensional nanomaterials with exceptional chemical and physical properties. These "new oxides" can be used in many niche technologies and applications such as nanoscale electronics and heterogeneous nanocatalysis. In this work, we study the formation of surface oxidic structures and motifs of Cu, supported on the Au(111) substrate, using first-principles density-functional theory calculations in conjunction with an ab initio atomistic thermodynamics model. In particular, we systematically examine and analyze the detailed atomic structure and surface energetics of various oxidic motifs of Cu on Au(111), in particular, p2, p2s, p2(6q6) and the newly suggested metastable p2(6q6) + O3, in comparison to both the binary O/Cu(111) and O/Au(111) systems. Depending on the oxygen atmosphere and the type of surface defects introduced in the oxidic layer, various non conventional, non-hexagonal surface oxidic motifs of Cu could be obtained. Our theoretical results agree with recent scanning tunneling microscopy (STM) experiments and we propose that metastable non-hexagonal surface motifs may pave a way to pursue further studies of these interesting complex surface oxidic layers on various metal supports. PMID- 26899926 TI - Glucose is a key driver for GLUT1-mediated nanoparticles internalization in breast cancer cells. AB - The mesenchymal state in cancer is usually associated with poor prognosis due to the metastatic predisposition and the hyper-activated metabolism. Exploiting cell glucose metabolism we propose a new method to detect mesenchymal-like cancer cells. We demonstrate that the uptake of glucose-coated magnetic nanoparticles (MNPs) by mesenchymal-like cells remains constant when the glucose in the medium is increased from low (5.5 mM) to high (25 mM) concentration, while the MNPs uptake by epithelial-like cells is significantly reduced. These findings reveal that the glucose-shell of MNPs plays a major role in recognition of cells with high-metabolic activity. By selectively blocking the glucose transporter 1 channels we showed its involvement in the internalization process of glucose coated MNPs. Our results suggest that glucose-coated MNPs can be used for metabolic-based assays aimed at detecting cancer cells and that can be used to selectively target cancer cells taking advantage, for instance, of the magnetic thermotherapy. PMID- 26899928 TI - Measurement of serum testosterone during androgenic suppression in patients with prostate cancer: A systematic review. AB - INTRODUCTION: Clinical practice guidelines recommend measuring serum testosterone (ST) during androgenic suppression (AS) to assess its efficacy and define castration resistance (CR). The objectives of this systematic review were to assess the level of scientific evidence that justify checking ST levels during AS, when to perform it and for what purpose. MATERIAL AND METHODS: We performed a search in PubMed with the following mesh terms: androgen suppression, testosterone, and prostate cancer. The search was narrowed to original articles published in English. RESULTS: We found 8 publications that analysed the clinical impact of ST concentrations during AS. In all of the series, ST was measured using chemiluminescent assays. However, only indirect methods based on liquid or gas chromatography for its extraction and subsequent quantification using mass spectrometry are recommended, especially for measuring low levels. The endpoints were specific survival and CR-free survival. Six studies were retrospective. The series were not uniform in terms of clinical stage, types of AS and ST assessment methods. In general, low ST levels (<20ng/dL or <32ng/dL) were related to longer CR-free survival. The measurements were performed every 3 or 6 months. Four studies confirmed the beneficial effect of adding bicalutamide when detecting microelevations above 50ng/dL. CONCLUSIONS: The level of scientific evidence justifying the measurement of ST during AS is low, and the methods employed for quantifying ST levels are inadequate. However, we consider it useful to check ST levels during AS, and there appears to be an association between low ST levels and better disease outcomes. In the event of microelevations above 50ng/dL, we recommend the administration of bicalutamide. PMID- 26899927 TI - The frequency and skewed T-cell receptor beta-chain variable patterns of peripheral CD4(+)CD25(+) regulatory T-cells are associated with hepatitis B e antigen seroconversion of chronic hepatitis B patients during antiviral treatment. AB - The frequency and T-cell receptor beta-chain variable (TCRBV) patterns of peripheral CD4(+)CD25(+) regulatory T-cells (Tregs) are ambiguously altered in chronic hepatitis B (CHB) patients following tenofovir disoproxil fumarate (TDF) treatment. Moreover, the clinical significance of these parameters in relation to hepatitis B e antigen (HBeAg) seroconversion (SC) is largely unknown. In this study, the circulation of Tregs in HBeAg-positive CHB patients was determined by flow cytometry, and the molecular profiles of frequent TCRBV patterns of Tregs were analyzed using a gene melting spectral pattern. The parameters, such as Treg frequency, the number of skewed TCRBV patterns, hepatitis B virus (HBV) DNA levels, and alanine aminotransferase (ALT) levels, were analyzed by comparing their associations in seroconverting and non-seroconverting patients following TDF treatment. The Treg frequency was significantly correlated with the ALT level in seroconverting but not in non-seroconverting patients. Similarly, skewed TCRBV patterns were remarkably associated with HBV DNA levels in the SC group. Six TCRBV families (BV3, BV11, BV12, BV14, BV20, and BV24) were more prevalent than other TCRBV members in seroconverting patients pretreated with TDF, while BV12, BV15, and BV22 were predominant in non-seroconverting patients during TDF treatment. Taken together, the preferential TCRBV patterns may be associated with immune responses related to SC. The dynamic frequency and skewed TCRBV patterns of peripheral Tregs could contribute to predicting SC in CHB patients. Moreover, the conserved TCRBV complementarity-determining region (CDR3) motif may be targeted to develop personalized immunotherapy for CHB patients. PMID- 26899931 TI - Quantifying intraclass correlations for count and time-to-event data. AB - The intraclass correlation is commonly used with clustered data. It is often estimated based on fitting a model to hierarchical data and it leads, in turn, to several concepts such as reliability, heritability, inter-rater agreement, etc. For data where linear models can be used, such measures can be defined as ratios of variance components. Matters are more difficult for non-Gaussian outcomes. The focus here is on count and time-to-event outcomes where so-called combined models are used, extending generalized linear mixed models, to describe the data. These models combine normal and gamma random effects to allow for both correlation due to data hierarchies as well as for overdispersion. Furthermore, because the models admit closed-form expressions for the means, variances, higher moments, and even the joint marginal distribution, it is demonstrated that closed forms of intraclass correlations exist. The proposed methodology is illustrated using data from agricultural and livestock studies. PMID- 26899932 TI - ERP variabilities as a function of reading maturation. PMID- 26899933 TI - Stereo-electroencephalography (SEEG) in children surgically cured of their epilepsy. AB - PURPOSE: SEEG in children has a low morbidity and leads to a good surgical outcome, in particular in younger patients. We analysed, in detail, the SEEG data of patients that were subsequently cured by surgery. METHODS: We selected the 48 children explored between 2009 and 2013 in our centre and surgically cured after SEEG-based resections with at least one-year follow-up. We retrospectively studied demographic and surgical data and paid particular attention to the data acquired during the invasive recording. Moreover, we compared the children younger than 5 years of age (group 1: 17 children) to those older than 5 years of age at the time of exploration (group 2: 31 patients). RESULTS: SEEG was well tolerated. Only one patient had slight intracerebral bleeding seen on the post operative CT-scan without any clinical consequence and which did not prevent the recording. SEEG explored at least four lobes in 59% of patients, either because of a suspected very widespread epileptogenic zone or because of the lack of a precise hypothesis. Auras were recorded only in group 2 (32% of patients, P=0.0009). Despite these difficulties, SEEG led to tailored resections including multilobar resections in 14% and infralobar resections in 69% of patients. The electrical pattern of seizures had no particularities as compared with adults. Interictal spikes and slow waves outside the resection zone were significantly less frequent in group 1 (P=0.02). In symptomatic epilepsies, the lesion matched the irritative zone in only 11% of patients and the ictal onset zone in 32% respectively. CONCLUSION: Our study confirms the low morbidity of SEEG in children. SEEG can disclose a limited epileptogenic zone. Our data suggest that the epileptic network is less complex in younger patients, which has to be confirmed by a quantitative analysis of SEEG signals. PMID- 26899934 TI - Central and peripheral motor drive to the palatal muscles. AB - AIM OF THE STUDY: To characterize the motor command of the soft palate muscles using a magnetic stimulation technique. MATERIAL AND METHODS: Motor evoked potentials (MEPs) were recorded in 10 right-handed and 5 left-handed subjects at the midline of the palate or on the right or left hemipalate to peripheral and cortical magnetic stimulation. RESULTS: Mean palatal MEP amplitude ranged from 0.06 to 0.26mV to peripheral stimulation and from 0.36 to 1.09mV to cortical stimulation. In hemipalate recordings, MEPs to peripheral stimulation had greater amplitude when recorded ipsilaterally to the stimulation side, whereas MEPs to cortical stimulation were symmetrical. In midline recordings, right-handed subjects showed greater palatal MEP amplitude to right (rather than left) peripheral stimulation and to left (rather than right) cortical stimulation. Mean palatal MEP latency ranged from 4.0 to 4.1ms to peripheral stimulation and from 9.0 to 10.2ms to cortical stimulation; mean central conduction time ranged from 4.9 to 6.2ms. CONCLUSION: Palatal MEPs were easily and reliably obtained, including selective responses in each hemipalate. A bilateral cortical command of the palate is supported by our results, with a possible predominant motor drive from the left hemisphere in right-handed subjects. PMID- 26899935 TI - One Health and EcoHealth: the same wine in different bottles? PMID- 26899937 TI - Do the Emotional Benefits of Optimism Vary Across Older Adulthood? A Life Span Perspective. AB - This study examined whether the emotional benefits of dispositional optimism for managing stressful encounters decrease across older adulthood. Such an effect might emerge because age-related declines in opportunities for overcoming stressors could reduce the effectiveness of optimism. This hypothesis was tested in a 6-year longitudinal study of 171 community-dwelling older adults (age range = 64-90 years). Hierarchical linear models showed that dispositional optimism protected relatively young participants from exhibiting elevations in depressive symptoms over time, but that these benefits became increasingly reduced among their older counterparts. Moreover, the findings showed that an age-related association between optimism and depressive symptoms was observed particularly during periods of enhanced, as compared to reduced, stress. These results suggest that dispositional optimism protects emotional well-being during the early phases of older adulthood, but that its effects are reduced in advanced old age. PMID- 26899936 TI - Octahedral Rotation Preferences in Perovskite Iodides and Bromides. AB - Phase transitions in ABX3 perovskites are often accompanied by rigid rotations of the corner-connected BX6 octahedral network. Although the mechanisms for the preferred rotation patterns of perovskite oxides are fairly well recognized, the same cannot be said of halide variants (i.e., X = Cl, Br, or I), several of which undergo an unusual displacive transition to a tetragonal phase exhibiting in phase rotations about one axis (a(0)a(0)c(+) in Glazer notation). To discern the chemical factors stabilizing this unique phase, we investigated a series of 12 perovskite bromides and iodides using density functional theory calculations and compared them with similar oxides. We find that in-phase tilting provides a better arrangement of the larger bromide and iodide anions, which minimizes the electrostatic interactions, improves the bond valence of the A-site cations, and enhances the covalency between the A-site metal and Br(-) or I(-) ions. The opposite effect is present in the oxides, with out-of-phase tilting maximizing these factors. PMID- 26899938 TI - Psychosurgery Reduces Uncertainty and Increases Free Will? A Review. AB - OBJECTIVE: A definition of free will is the ability to select for or against a course of action to fulfill a desire, without extrinsic or intrinsic constraints that compel the choice. Free will has been linked to the evolutionary development of flexible decision making. In order to develop flexibility in thoughts and behavioral responses, learning mechanisms have evolved as a modification of reflexive behavioral strategies. The ultimate goal of the brain is to reduce uncertainty inherently present in a changing environment. A way to reduce the uncertainty, which is encoded by the rostral anterior cingulate, is to make multiple predictions about the environment which are updated in parallel by sensory inputs. The prediction/behavioral strategy that fits the sensory input best is then selected, becomes the next percept/behavioral strategy, and is stored as a basis for future predictions. Acceptance of predictions (positive feedback) is mediated via the accumbens, and switching to other predictions by the dorsal anterior cingulate cortex (ACC) (negative feedback). Maintenance of a prediction is encoded by the pregenual ACC. Different cingulate territories are involved in rejection, acceptance and maintenance of predictions. Free will is known to be decreased in multiple psychopathologies, including obsessive compulsive disorder and addictions. METHODOLOGY: In modern psychosurgery three target structures exist for obsessive compulsive disorder and addiction: the dorsal ACC, the nucleus accumbens, and/or the anterior limb of the internal capsula. Research in all three areas reports favorable results with acceptable side effects. Psychosurgical interventions seem to exert their effect by a common final common pathway mediated via the pregenual ACC. CONCLUSION: Successful neuromodulation increases the capacity to choose from different options for the affected individual, as well as inhibiting unwanted options, therefore increasing free will and free won't. PMID- 26899939 TI - Consultation via telemedicine and access to operative care for patients with head and neck cancer in a Veterans Health Administration population. AB - BACKGROUND: The purpose of this study was to evaluate a telemedicine model that utilizes an audiovisual teleconference as a preoperative visit. METHODS: Veterans Health Administration (VHA) patients with head and neck cancer at 2 remote locations were provided access to the Palo Alto Veterans Affairs (PAVA) Health Care System otolaryngology department via the telemedicine protocol: tissue diagnosis and imaging at the patient site; data review at PAVA; and a preoperative teleconference connecting the patient to PAVA. Operative care occurred at PAVA. Follow-up care was provided remotely via teleconference. RESULTS: Fifteen patients were evaluated. Eleven underwent surgery, 4 with high grade neoplasms (carcinoma). Average time from referral to operation was 28 days (range, 17-36 days) and 72 (range, 31-108 days), respectively, for high-grade and low-grade groups. The average patient was spared 28 hours traveling time and $900/patient was saved on travel-related costs. CONCLUSION: A telemedicine model enables timely access to surgical care and permits considerable savings among select VHA patients with head and neck cancer. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: 925-929, 2016. PMID- 26899940 TI - Localized melanoma in older patients, the impact of increasing age and comorbid medical conditions. AB - BACKGROUND: Elderly patients experience a different spectrum of disease and poorer outcomes than younger patients. This study investigated the impact of age and medical comorbidities on the management and outcome of patients >=65 years. METHODS: A retrospective review of all patients >=65 years (481 patients with 525 primary melanomas) presenting with AJCC clinical stage I-II melanoma to an Australian cancer centre between 2000 and 2008. RESULT: The median age was 74 years (65-94) with a male predominance (313 males, 65.0%) and median tumour thickness of 1.90 mm (IQR = 0.40-2.90, T1 = 33%, T2 = 20%, T3 = 24%, T4 = 23%). Inadequate surgical margins of excision (<10 mm) were common in older patients independent of site, thickness and ulceration (OR = 1.04, 95%CI = 1.00-1.07, p = 0.038). Inadequate excision margins were strongly associated with time to local recurrence, independent of age, thickness, ulceration and mitotic rate (HR = 3.00, 95%CI = 1.49-6.03, p = 0.0021), but not time to progression (p = 0.10) or disease specific survival (DSS, p = 0.27). Overall survival (OS) was strongly related to increasing age (HR = 1.04, 95%CI = 1.01-1.07, p = 0.015) and comorbid medical conditions (HR = 1.26, 95%CI = 1.12-1.42, p < 0.001), as assessed by the Charlson comorbidity index (CCI). DSS was significantly related to CCI (HR = 1.20, 95%CI = 1.01-1.42, p = 0.041) and not age (p = 0.46), when adjusting for thickness, ulceration and mitotic rate on multivariate analysis. CONCLUSION: Older patients present with poor prognosis melanomas yet are less likely to receive adequate surgical excision margins resulting in higher rates of local recurrence. In melanoma patients >=65 years, the increasing number of medical comorbidities explains much of the age related variations in OS and DSS and should be considered when planning treatment. PMID- 26899941 TI - Physical function of the upper limb after breast cancer surgery. Results from the SOUND (Sentinel node vs. Observation after axillary Ultra-souND) trial. AB - BACKGROUND: The SOUND (Sentinel node vs. Observation after axillary Ultra-souND) trial is an ongoing prospective randomized study comparing sentinel node biopsy vs. no axillary surgical staging in patients with small breast cancer and negative pre-operative ultra-sound of the axilla. PATIENTS AND METHODS: The first 180 recruited patients were administered the QuickDASH (Disability Arm and Shoulder) questionnaire at different time points (before surgery, 1 week, 6 months and 1 year after surgery) to evaluate the physical function of the ipsilateral upper limb, The QuickDASH score ranges from 0 (no disability) to 100 (complete disability). RESULTS: 176 patients were available for analysis (94 in SNB arm and 82 in observation arm). The two groups were comparable with respect to age, tumor characteristics and treatments. Pre-surgery score values were 3.0% and 2.7% in the SNB arm and observation arm, respectively (P = 0.730). One week after surgery, the score increased to 24.0% in the SNB arm and 10.6% in the observation arm (P < 0.001). After 6 and 12 months, the score decreased in both arms to values similar to baseline values. The overall trend in time of the score was significantly different between the two arms (P < 0.001), even after the exclusion of five patients who received AD in the SNB arm (P < 0.001). CONCLUSIONS: Patients who underwent SNB had a significantly higher rate of disability in the early post-operative period compared to patients who did not. The avoidance of SNB might translate into a considerable reduction of physical and emotional distress. PMID- 26899942 TI - Do we need new high-risk criteria for surgically treated renal cancer patients to improve the outcome of future clinical trials in the adjuvant setting? Results of a comprehensive analysis based on the multicenter CORONA database. AB - BACKGROUND: Since there is still an unmet need for potent adjuvant strategies for renal cancer patients with high progression risk after surgery, several targeted therapies are currently evaluated in this setting. We analyzed whether inclusion criteria of contemporary trials (ARISER, ASSURE, SORCE, EVEREST, PROTECT, S-TRAC, ATLAS) correctly identify high-risk patients. METHODS: The study group comprised 8873 patients of the international CORONA-database after surgery for non metastatic renal cancer without any adjuvant treatment. Patients were divided into potentially eligible high-risk and assumable low-risk patients who didn't meet inclusion criteria of contemporary adjuvant clinical trials. The ability of various inclusion criteria for disease-free survival (DFS) prediction was evaluated by Harrell's c-index. RESULTS: During a median follow-up of 53 months 15.2% of patients experienced recurrence (5-year-DFS 84%). By application of trial inclusion criteria, 24% (S-TRAC) to 47% (SORCE) of patients would have been eligible for enrollment. Actual recurrence rates of eligible patients ranged between 29% (SORCE) and 37% (S-TRAC) opposed to <10% in excluded patients. Highest Hazard Ratio for selection criteria was proven for the SORCE-trial (HR 6.42; p < 0.001), while ASSURE and EVEREST reached the highest c-index for DFS prediction (both 0.73). In a separate multivariate Cox-model, two risk-groups were identified with a maximum difference in 5-year-DFS (94% vs. 61%). CONCLUSION: Results of contemporary adjuvant clinical trials will not be comparable as inclusion criteria differ significantly. Risk assessment according to our model might improve patient selection in clinical trials by defining a high-risk group (28% of all patients) with a 5-year-recurrence rate of almost 40%. PMID- 26899943 TI - Preoperative treatment with gemcitabine plus nab-paclitaxel is a safe and effective chemotherapy for pancreatic adenocarcinoma. AB - INTRODUCTION: Recently, novel chemotherapeutic agents like nab-paclitaxel and gemcitabine demonstrated a survival benefit over gemcitabine alone in metastatic pancreatic cancer. However, there are limited clinical results using this chemotherapy in potentially resectable pancreatic adenocarcinoma. Our aim is to report the oncological results of patients affected by potentially resectable pancreatic adenocarcinoma that underwent surgery after a combination of gemcitabine and nab-paclitaxel. METHODS: A total of 25 patients have been included. We evaluated: (1) Drug toxicity; (2) tumoral response (tumoral size at CT scan, SUV of FDG PET-CT scan and CA 19.9; (3) resection rate; (4) R0 resection rate and histopathological response and (5) survival and disease free survival. RESULTS: Overall treatment was well tolerated. Treatment resulted in a statistical decrease of CA19-9 (p = 0.019) tumoral size (p = 0.04) and SUV (p = 0.004). The resection rate was 68% (17/25 patients). All specimens were R0 and 13 of 17 specimens had major pathological regressions (complete and important response). Median survival and medial disease free survival of patients that underwent surgery was 21 months and 19 months, respectively at a mean follow up of 38.5 months. CONCLUSIONS: This data suggests that nab-paclitaxel and gemcitabine is a safe and effective neoadjuvant treatment for potentially resectable pancreatic adenocarcinoma. This promising data should be confirmed in larger, randomized studies. PMID- 26899945 TI - Catalytic selective deuteration of halo(hetero)arenes. AB - Deuterium labeled aromatic and heteroaromatic compounds are synthesized in good to excellent yields with >98% deuterium purity via palladium catalyzed deuterodehalogenation reaction using commercially available and inexpensive reagents. Selective deuteration of bromoaniline is also demonstrated without H/D exchange in an amino N-H group. PMID- 26899944 TI - Progestins alter photo-transduction cascade and circadian rhythm network in eyes of zebrafish (Danio rerio). AB - Environmental progestins are implicated in endocrine disruption in vertebrates. Additional targets that may be affected in organisms are poorly known. Here we report that progesterone (P4) and drospirenone (DRS) interfere with the photo transduction cascade and circadian rhythm network in the eyes of zebrafish. Breeding pairs of adult zebrafish were exposed to P4 and DRS for 21 days with different measured concentrations of 7-742 ng/L and 99-13'650 ng/L, respectively. Of totally 10 key photo-transduction cascade genes analyzed, transcriptional levels of most were significantly up-regulated, or normal down-regulation was attenuated. Similarly, for some circadian rhythm genes, dose-dependent transcriptional alterations were also observed in the totally 33 genes analyzed. Significant alterations occurred even at environmental relevant levels of 7 ng/L P4. Different patterns were observed for these transcriptional alterations, of which, the nfil3 family displayed most significant changes. Furthermore, we demonstrate the importance of sampling time for the determination and interpretation of gene expression data, and put forward recommendations for sampling strategies to avoid false interpretations. Our results suggest that photo-transduction signals and circadian rhythm are potential targets for progestins. Further studies are required to assess alterations on the protein level, on physiology and behavior, as well as on implications in mammals. PMID- 26899946 TI - Using Fourier transform infrared spectroscopy to evaluate biological effects induced by photodynamic therapy. AB - BACKGROUND AND OBJECTIVE: Vibrational spectroscopic methods associated with multivariate statistical techniques have been succeeded in discriminating skin lesions from normal tissues. However, there is no study exploring the potential of these techniques to assess the alterations promoted by photodynamic effect in tissue. The present study aims to demonstrate the ability of Fourier Transform Infrared (FTIR) spectroscopy on Attenuated total reflection (ATR) sampling mode associated with principal component-linear discriminant analysis (PC-LDA) to evaluate the biochemical changes caused by photodynamic therapy (PDT) in skin neoplastic tissue. MATERIALS AND METHODS: Cutaneous neoplastic lesions, precursors of squamous cell carcinoma (SCC), were chemically induced in Swiss mice and submitted to a single session of 5-aminolevulinic acid (ALA)-mediated PDT. Tissue sections with 5 MUm thickness were obtained from formalin-fixed paraffin-embedded (FFPE) and processed prior to the histopathological analysis and spectroscopic measurements. Spectra were collected in mid-infrared region using a FTIR spectrometer on ATR sampling mode. Principal Component-Linear Discriminant Analysis (PC-LDA) was applied on preprocessed second derivatives spectra. Biochemical changes were assessed using PCA-loadings and accuracy of classification was obtained from PC-LDA . RESULTS: Sub-bands of Amide I (1,624 and 1,650 cm(-1) ) and Amide II (1,517 cm(-1) ) indicated a protein overexpression in non-treated and post-PDT neoplastic tissue compared with healthy skin, as well as a decrease in collagen fibers (1,204, 1,236, 1,282, and 1,338 cm(-1) ) and glycogen (1,028, 1,082, and 1,151 cm(-1) ) content. Photosensitized neoplastic tissue revealed shifted peak position and decreased beta-sheet secondary structure of proteins (1,624 cm(-1) ) amount in comparison to non-treated neoplastic lesions. PC-LDA score plots discriminated non-treated neoplastic skin spectra from post-PDT cutaneous lesions with accuracy of 92.8%, whereas non-treated neoplastic skin was discriminated from healthy tissue with 93.5% accuracy and post-PDT cutaneous lesions was discriminated from healthy tissue with 89.7% accuracy. CONCLUSION: PC-LDA was able to discriminate ATR-FTIR spectra of non-treated and post-PDT neoplastic lesions, as well as from healthy skin. Thus, the method can be used for early diagnosis of premalignant skin lesions, as well as to evaluate the response to photodynamic treatment. Lasers Surg. Med. 48:538-545, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26899948 TI - Quantification of Epidermal Filaggrin in Human Skin and its Response to Skin Irritation. PMID- 26899949 TI - Trajectories of emotional-behavioral difficulty and academic competence: A 6 year, person-centered, prospective study of affluent suburban adolescents. AB - This longitudinal study of affluent suburban youth (N = 319) tracked from 6th to 12th grade is parsed into two segments examining prospective associations concerning emotional-behavioral difficulties and academic achievement. In Part 1 of the investigation, markers of emotional-behavioral difficulty were used to cluster participants during 6th grade. Generalized estimating equations were then used to document between-cluster differences in academic competence from 6th to 12th grade. In Part 2 of the study, indicators of academic competence were used to cluster the same students during 6th grade, and generalized estimating equations were used to document between-cluster differences in emotional behavioral difficulty from 6th to 12th grade. The results from Part 1 indicated that patterns of emotional-behavioral difficulty during 6th grade were concurrently associated with poorer grades and classroom adjustment with some group differences in the rate of change in classroom adjustment over time. In Part 2, patterns of academic competence during 6th grade were concurrently associated with less emotional-behavioral difficulty and some group differences in the rate of change in specific forms of emotional-behavioral difficulty over time. These results suggest that the youth sampled appeared relatively well adjusted and any emotional-behavioral-achievement difficulty that was evident at the start of middle school was sustained through the end of high school. PMID- 26899951 TI - Molecular dynamics simulations of the atom packing characteristics of three deformed silver nanoparticles at room temperature. AB - Deformation is of significance in controlling the shape of materials, but the key structural information of metal nanoparticles is still limited. Molecular dynamics simulations are performed to explore the microscopic details of atom packing differences in three deformed silver nanoparticles with one atom difference. Analytical tools are used to demonstrate the effects of external load and surface atoms of particles on the packing patterns in these deformed nanoparticles including internal energy per atom, pair numbers, and pair distribution functions as well as cross-sectional images. The simulation results show that under small compression, the particles present elastic behaviors. The increasing compression results in the sliding of the atoms in different parts of these particles, and some interfaces are formed between these parts. As the external load becomes large, these deformed particles are compressed into the thickness of several atomic layers. The unloaded particles present different behaviors. PMID- 26899950 TI - Hyperthermia and Radiation Therapy in Locoregional Recurrent Breast Cancers: A Systematic Review and Meta-analysis. AB - PURPOSE: To conduct a systematic review and meta-analysis to evaluate the outcome of hyperthermia (HT) and radiation therapy (RT) in locally recurrent breast cancers (LRBCs). METHODS AND MATERIALS: A total of 708 abstracts were screened from 8 databases according to the PRISMA guidelines. Single-arm and 2-arm studies, treating LRBCs with HT and RT but without surgery (for local recurrence) or concurrent chemotherapy were considered. The evaluated endpoint was complete response (CR). RESULTS: Thirty-one full text articles, pertaining to 34 studies, were shortlisted for the meta-analysis. Eight were 2-arm (randomized, n=5; nonrandomized, n=3), whereas 26 were single-arm studies. In all, 627 patients were enrolled in 2-arm and 1483 in single-arm studies. Patients were treated with a median of 7 HT sessions, and an average temperature of 42.5 degrees C was attained. Mean RT dose was 38.2 Gy (range, 26-60 Gy). Hyperthermia was most frequently applied after RT. In the 2-arm studies, a CR of 60.2% was achieved with RT + HT versus 38.1% with RT alone (odds ratio 2.64, 95% confidence interval [CI] 1.66-4.18, P<.0001). Risk ratio and risk difference were 1.57 (95% CI 1.25 1.96, P<.0001) and 0.22 (95% CI 0.11-0.33, P<.0001), respectively. In 26 single arm studies, RT + HT attained a CR of 63.4% (event rate 0.62, 95% CI 0.57-0.66). Moreover, 779 patients had been previously irradiated (696 from single-arm and 83 from 2-arm studies). A CR of 66.6% (event rate 0.64, 95% CI 0.58-0.70) was achieved with HT and reirradiation (mean +/- SD dose: 36.7 +/- 7.7 Gy). Mean acute and late grade 3/4 toxicities with RT + HT were 14.4% and 5.2%, respectively. CONCLUSIONS: Thermoradiation therapy enhances the likelihood of CR rates in LRBCs over RT alone by 22% with minimal acute and late morbidities. For even those previously irradiated, reirradiation with HT provides locoregional control in two-thirds of the patients. Thermoradiation therapy could therefore be considered as an effective and safe palliative treatment option for LRBCs. PMID- 26899947 TI - Collagen VII Half-Life at the Dermal-Epidermal Junction Zone: Implications for Mechanisms and Therapy of Genodermatoses. AB - The tissue half-life of proteins largely determines treatment frequency of non gene-editing-based therapies targeting the cause of genodermatoses. Surprisingly, such knowledge is missing for a vast number of proteins involved in pathologies. The dermal-epidermal junction zone is believed to be a rather static structure, but to our knowledge no detailed analysis of the stability of proteins within this zone has been performed. Here, we addressed the in vivo half-life of collagen type VII using genetic ablation of its expression and therapeutic introduction of exogenous collagen VII in a preclinical model. A similar in vivo stability of collagen VII was observed in the skin, tongue, and esophagus, with a half-life of about 1 month. Collagen VII expressed by intradermally injected mesenchymal stromal cells also exhibited a similar half-life. Our study provides key information needed for the development of protein replacement or cell-based therapies for dystrophic epidermolysis bullosa caused by genetic deficiency of collagen VII. Moreover, by showing what we define as an intermediate half-life of collagen VII, our study challenges the view of the dermal-epidermal junction zone as a static structure with very slow turnover. PMID- 26899952 TI - The free neural grafting for recurrent nerve laceration Experimental study in rabbit. AB - AIM: The most dreaded complication of thyroidectomy is recurrent laryngeal nerve damage, which is most of the time hardly irreversible. In our experimental study we researched the use of free nerve grafts in the treatment of laryngeal nerve damage in rabbit. MATERIAL AND METHODS: There were three groups in our study. In the first group, the recurrent laryngeal nerve was severed and then a free nerve graft was interposed between the phrenic nerve and distal end of recurrent laryngeal nerve. In the second group, a defect in the continuity of the laryngeal nerve was created. The two ends of the nerve were joined together later by an interposed free nerve graft. In the third group, only a defect in the recurrent nerve was created without any attempt at uniting the ends together so that these latter subjects could be assigned as control group. In the evaluation process we performed laryngeal endoscopy, laryngeal EMG and histopathologic examination. RESULTS: On the 21. day of trial, in the first and second group vocal cord movements were detected on the laryngoscopy along with regeneration waves on EMG. In the third group there was no vocal cord movements on the side where a neural damage was created intentionally. On EMG there was degeneration waves as opposed to regeneration waves seen in the first and second groups. Histopathologic findings were similar. CONCLUSIONS: Recurrrent laryngeal nerve paralysis is an unwanted complication because it causes permenant sequela. Studies which intend to find a cure for this complication are increasing in number. We aim to find new approaches to cure patients suffering from this devastating complication as well. In our exprerimental study, vocal cord movements were reproduced without causing diaphragmatic paralysis. We believe the results of our study promise to relieve the suffering of patients. The results are encouraging. KEY WORDS: Muscle, Rat model, Reinnervation, Surgery. PMID- 26899953 TI - Immunity factor contributes to altered brain functional networks in individuals at risk for Alzheimer's disease: Neuroimaging-genetic evidence. AB - Clusterin (CLU) is recognized as a secreted protein that is related to the processes of inflammation and immunity in the pathogenesis of Alzheimer's disease (AD). The effects of the risk variant of the C allele at the rs11136000 locus of the CLU gene are associated with variations in the brain structure and function. However, the relationship of the CLU-C allele to architectural disruptions in resting-state networks in amnestic mild cognitive impairment (aMCI) subjects (i.e., individuals with elevated risk of AD) remains relatively unknown. Using resting-state functional magnetic resonance imaging and an imaging genetic approach, this study investigated whether individual brain functional networks, i.e., the default mode network (DMN) and the task-positive network, were modulated by the CLU-C allele (rs11136000) in 50 elderly participants, including 26 aMCI subjects and 24 healthy controls. CLU-by-aMCI interactions were associated with the information-bridging regions between resting-state networks rather than with the DMN itself, especially in cortical midline regions. Interestingly, the complex communications between resting-state networks were enhanced in aMCI subjects with the CLU rs11136000 CC genotype and were modulated by the degree of memory impairment, suggesting a reconstructed balance of the resting-state networks in these individuals with an elevated risk of AD. The neuroimaging-genetic evidence indicates that immunity factors may contribute to alterations in brain functional networks in aMCI. These findings add to the evidence that the CLU gene may represent a potential therapeutic target for slowing disease progression in AD. PMID- 26899954 TI - Carriage of beta-lactamase-producing Enterobacteriaceae among nursing home residents in north Lebanon. AB - BACKGROUND: Multidrug-resistant (MDR) Enterobacteriaceae can cause severe infections with high morbidity, mortality, and health care costs. Individuals can be fecal carriers of these resistant organisms. Data on the extent of MDR Enterobacteriaceae fecal carriage in the community setting in Lebanon are very scarce. The aim of this study was to investigate the fecal carriage of MDR Enterobacteriaceae among the elderly residents of two nursing homes located in north Lebanon. METHODS: Over a period of 4 months, five fecal swab samples were collected from each of 68 elderly persons at regular intervals of 3-4 weeks. Fecal swabs were subcultured on selective media for the screening of resistant organisms. The phenotypic detection of extended-spectrum beta-lactamase (ESBL), AmpC, metallo-beta-lactamase (MBL), and Klebsiella pneumoniae carbapenemase (KPC) production was performed using the beta-lactamase inhibitors ethylenediaminetetraacetic acid, phenylboronic acid, and cloxacillin. A temocillin disk was used for OXA-48. Multiplex PCRs were used for the genotypic detection of ESBL and carbapenemase genes, and sequencing was performed to identify CTX-M-15. The medical records of each subject were reviewed on a regular basis in order to assess the risk factors associated with MDR Enterobacteriaceae fecal carriage. RESULTS: Over the study period, 76.5% of the recruited elderly persons were at least one-time carriers. A total of 178 isolates were obtained. Phenotypic testing revealed that 91.5% of them were ESBL producers, 4% were AmpC producers, 2.8% were co-producers of ESBL and AmpC, and 1.7% were co-producers of OXA-48 and ESBL. Recent antibiotic intake was found to be the only independent risk factor associated with the fecal carriage of MDR Enterobacteriaceae. CONCLUSIONS: The high prevalence of MDR Enterobacteriaceae detected in this study and the emergence of carbapenem resistance is alarming. Efficient infection control measures and antibiotic stewardship programs are urgently needed in these settings in order to limit the spread of resistant strains. PMID- 26899955 TI - Molecular Characterization of Wild Type Measles Virus from Adult Patients in Northern China, 2014. AB - OBJECTIVES: In this study, we studied the N and H genes from wild type measles viruses (MeVs) isolated during the 2013-2014 outbreak. METHODS: Clinical samples were collected, and the genotyping, phylogenetic analysis were performed. RESULTS: The vaccination rate of the study population was 4%. Genotype H1a was the predominant genotype. Wild type viruses were classified into clusters A and B, C and may have different origins. N-450 sequences from wild type viruses were highly homologous with, and likely evolved from MeVs circulating in Tianjing and Henan in 2012. MVs/Shenyang.CHN/18.14/3 could have evolved from MeVs from Liaoning, Beijing, Hebei, Heilongjiang, Henan, Jilin, and Tianjin. Our data suggested that one or more of the same viruses circulated between Beijing, Shenyang, Hong Kong, Taiwan and Berlin. CONCLUSIONS: Important factors contributing to outbreaks could include weak vaccination coverage, poor vaccination strategies, and migration of adult workers between cities, countries, and from rural areas to urban areas. PMID- 26899956 TI - Molecular characterization of hepatitis B virus from chronically-infected patients in Niamey, Niger. AB - OBJECTIVES: In Niger, 65% of hepatocarcinoma and 75% of cirrhosis cases were due to hepatitis B virus (HBV). We studied the genotypic characteristics of HBsAg in chronically HBV-infected patients in Niamey. METHODS: We studied prospectively HBV genotypic patterns among hospitalized patients with HBV infection in the National Hospital of Niamey, Niger. Patients were screened for hepatitis B surface antigen (HBsAg) and HBV genotyping was performed on the HBsAg-positive patients. RESULTS: In this study, we have confirmed the predominance of the HBV genotype E (HBV-E) in Niger and have identified 2 recombinant forms including HBV E/D and HBV-A3/E reported previously among blood donors in Niger and Ghana, respectively. Amino acid substitutions found in HBV sequences obtained here included P120T, S143L, G145A and A194T. These substitutions were characterized as being associated with modified antigenicity and, notably, with impaired serological detection of HBsAg, while the A194T variant was found to have a controversial role in reduced susceptibility to tenofovir. CONCLUSIONS: We have identified two recombinant HBV forms and rare genotypic patterns in Niger that may affect hepatitis B surface antigen antigenicity, and improve current knowledge of epidemiological, clinical and virological patterns of hepatitis B in this country. PMID- 26899957 TI - Non-invasive ventilation with neurally adjusted ventilatory assist in newborns. AB - Neurally adjusted ventilatory assist (NAVA) is a mode of ventilation in which both the timing and degree of ventilatory assist are controlled by the patient. Since NAVA uses the diaphragm electrical activity (Edi) as the controller signal, it is possible to deliver synchronized non-invasive NAVA (NIV-NAVA) regardless of leaks and to monitor continuously patient respiratory pattern and drive. Advantages of NIV-NAVA over conventional modes include improved patient ventilator interaction, reliable respiratory monitoring and self-regulation of respiratory support. In theory, these characteristics make NIV-NAVA an ideal mode to provide effective, appropriate non-invasive support to newborns with respiratory insufficiency. NIV-NAVA has been successfully used clinically in neonates as a mode of ventilation to prevent intubation, to allow early extubation, and as a novel way to deliver nasal continuous positive airway pressure. The use of NAVA in neonates is described with an emphasis on studies and clinical experience with NIV-NAVA. PMID- 26899958 TI - Open reduction and internal fixation of rib fractures in polytrauma patients with flail chest. AB - BACKGROUND: Open reduction and internal fixation (ORIF) of fractured ribs for flail chest is safe and effective but who is most likely to benefit is unknown. Our purpose is to compare ORIF with nonoperative management (NOM) in polytrauma patients. METHODS: Albany Medical Center Hospital Trauma Registry was queried for adult patients with flail chest admitted over 7 years. RESULTS: Eighty-six patients with radiographic flail chest were identified who met inclusion criteria. The 41 ORIF and 45 NOM patients had similar demographics and injury severity. Hospital length of stay and intensive care unit length of stay were significantly longer in the ORIF group than that of the NOM group. There was a trend toward longer time on the ventilator in the ORIF group. CONCLUSIONS: In this retrospective study, patients treated by ORIF had longer hospitalization and ventilator duration. Future studies should be designed to optimally identify patients who are most likely to benefit from ORIF. PMID- 26899959 TI - Injury to the conduction system: management of life-threatening arrhythmias after penetrating cardiac trauma. AB - BACKGROUND: Life-threatening conduction abnormalities after penetrating cardiac injuries (PCIs) are rare, and rapid identification and treatment of these arrhythmias are critical to survival. This study highlights diagnosis and management strategies for conduction abnormalities after PCI. METHODS: Patients with life-threatening arrhythmias after PCI were identified at an urban, level I trauma center registry. RESULTS: Seventy-one patients survived to reach the hospital after PCI. Of these, 3 (4%) survivors (male = 3, mean age 41.3, median injury severity score = 25) had critical conduction abnormalities after cardiorrhaphy. All patients had multichamber and atrioventricular nodal injury. After initial cardiorrhaphy and control of hemorrhage, all patients had sustained hypotension with bradycardia from complete heart block. Two patients had ventricular septal defects requiring repair. All 3 patients survived. CONCLUSIONS: Rapid recognition of injury to the cardiac conduction system after PCI as a source of sustained hypotension is essential to early restoration of cardiac function and survival. PMID- 26899960 TI - Glucose- and glycaemic factor-lowering effects of probiotics on diabetes: a meta analysis of randomised placebo-controlled trials. AB - This meta-analysis examined the effect of probiotics on glucose and glycaemic factors in diabetes and its associated risk factors. All randomised-controlled trials published in English in multiple databases from January 2000 to June 2015 were systematically searched. Only studies that addressed glucose- and glycaemic related factors as outcome variables were included. The main outcomes of interest in trials were mean changes in glucose, HbA1c, insulin and homoeostasis model assessment-estimated insulin resistance (HOMA-IR). Using the Physiotherapy Evidence Database (PEDro) scale to assess the quality of studies, a total of eleven studies with 614 subjects were included. The pooled mean difference and effect size with a 95% CI were extracted using a random-effect model. It was found that there are statistically significant pooled mean differences between the probiotics and the placebo-controlled groups on the reduction of glucose ( 0.52 mmol/l, 95% CI -0.92, -0.11 mmol/l; P=0.01) and HbA1c (-0.32%, 95% CI -0.57, -0.07%; P=0.01). There was no statistically significant pooled mean difference between the probiotics and the placebo-controlled groups on the reduction of insulin (-0.48 uIU/ml, 95% CI -1.34, 0.38 uIU/ml; P=0.27) and HOMA-IR (pooled effect of -0.44, 95% CI -1.57, 0.70; P=0.45). Meta-regression analysis identified that probiotics had significant effects on reduction of glucose, HbA1c, insulin and HOMA-IR in participants with diabetes, but not in participants with other risk factors. The present meta-analysis suggested that probiotics may be used as an important dietary supplement in reducing the glucose metabolic factors associated with diabetes. PMID- 26899962 TI - Results of a fracture liaison service on hip fracture patients in an open healthcare system. AB - We assessed osteoporosis management in patients admitted for rehabilitation of acute hip fracture to an open system community hospital before and after institution of a fracture liaison service (FLS). Pre-FLS, we surveyed 60 patients 4-6 months after hip fracture. Subsequently, the FLS program performed routine consultations, and recommended lab, bone density testing (BMD) and osteoporosis medication. FLS program outcomes were assessed by survey in 75 patients after hip fracture. In the pre-FLS population, after hip fracture, 55 % changed calcium intake, 48 % changed vitamin D intake, and 35 % obtained a BMD. Osteoporosis medication was taken by 38 % before and 33 % after hip fracture. Post-FLS, 56 % changed calcium intake, 68 % changed vitamin D intake and 65 % obtained a BMD. Post-FLS, osteoporosis medication was taken by 21 % of patients before and 19 % after hip fracture. Our FLS program in hip fracture patients improved non pharmacologic measures, but not the use of osteoporosis medication. PMID- 26899961 TI - Modeling the effects of extracellular potassium on bursting properties in pre Botzinger complex neurons. AB - There are many types of neurons that intrinsically generate rhythmic bursting activity, even when isolated, and these neurons underlie several specific motor behaviors. Rhythmic neurons that drive the inspiratory phase of respiration are located in the medullary pre-Botzinger Complex (pre-BotC). However, it is not known if their rhythmic bursting is the result of intrinsic mechanisms or synaptic interactions. In many cases, for bursting to occur, the excitability of these neurons needs to be elevated. This excitation is provided in vitro (e.g. in slices), by increasing extracellular potassium concentration (K out) well beyond physiologic levels. Elevated K out shifts the reversal potentials for all potassium currents including the potassium component of leakage to higher values. However, how an increase in K out , and the resultant changes in potassium currents, induce bursting activity, have yet to be established. Moreover, it is not known if the endogenous bursting induced in vitro is representative of neural behavior in vivo. Our modeling study examines the interplay between K out, excitability, and selected currents, as they relate to endogenous rhythmic bursting. Starting with a Hodgkin-Huxley formalization of a pre-BotC neuron, a potassium ion component was incorporated into the leakage current, and model behaviors were investigated at varying concentrations of K out. Our simulations show that endogenous bursting activity, evoked in vitro by elevation of K out , is the result of a specific relationship between the leakage and voltage dependent, delayed rectifier potassium currents, which may not be observed at physiological levels of extracellular potassium. PMID- 26899963 TI - Suppression of prostate cancer progression by cancer cell stemness inhibitor napabucasin. AB - A small population of cells with stem cell-like properties in prostate cancer (PCa), called prostate cancer stem cells (PrCSCs) or prostate stemness-high cancer cells, displays highly tumorigenic and metastatic features and may be responsible for the therapy resistance. A small molecule, napabucasin (BBI608), recently have been identified with suppression of stemness-high cancer cells in a variety of cancers. However, the effects of napabucasin on PCa cells as well as PrCSCs isolated from PCa cells have not yet been defined. The effect of napabucasin on PCa cells in cell proliferation, colony formation, and cell migration in vitro were measured by MTS, colony formation assay, and Transwell, respectively. Flow cytometry was employed to evaluate cell cycle and cell apoptosis, and the effect on tumorigenesis in vivo was examined by tumor growth assays. Furthermore, the role of napabucasin on self-renewal and survival of PrCSCs was evaluated by their ability to grow spheres and cell viability assay, respectively. Western Blot and qRT-PCR were used to determine the effect of napabucasin on the expressions of stemness markers. Decrease in cell viability, colony formation, migration, and survival with cell cycle arrest, higher sensitivity to docetaxel in vitro, and repressed tumorigenesis in vivo was observed upon napabucasin treatment. More importantly, napabucasin can obviously inhibit spherogenesis and even kill PrCSCs in vitro. Downregulation of stemness markers was observed after PrCSCs were treated with napabucasin. This study demonstrates that napabucasin may be a novel approach in the treatment of advanced PCa, specifically for castration-resistant prostate cancer (CRPC). PMID- 26899964 TI - S100b Induces Expression of Myoglobin in APbeta Treated Neuronal Cells In Vitro: A Possible Neuroprotective Mechanism. AB - BACKGROUND: In this study, human neuroblastoma cells (IMR32) treated with Amyloid Beta Peptide (APbeta), were used as model to evaluate the molecular basis of protective role of S100b, a neurotrophic factor and neuronal survival protein, highly expressed by reactive astrocytes close to amyloid deposition in the cortex of Alzheimer's patients. The aim of this work is to value the effect of S100b on ROS production in cells treated with Amyloid Beta Peptide and the subsequent influence on globin gene expression. METHOD: In this study we investigated the effect of S100b on ROS production and on globin gene expression in human neuroblastoma cells (IMR32) treated with Amyloid Beta Peptide (APbeta). RESULTS: Our results have shown that at nanomolar concentrations, S100b protects cells against AP. mediated cytotoxicity and the protective mechanism could be related, almost in part, to the control of ROS production through an over expression of Myoglobin gene. CONCLUSION: In light of our results, we speculate that over expression of the Myoglobin gene could be read as a possible attempt of the cell to increase the scavengers of reactive oxygen species (ROS). PMID- 26899965 TI - Magnetophoretic-based microfluidic device for DNA Concentration. AB - Nucleic acids serve as biomarkers of disease and it is highly desirable to develop approaches to extract small number of such genomic extracts from human bodily fluids. Magnetic particles-based nucleic acid extraction is widely used for concentration of small amount of samples and is followed by DNA amplification in specific assays. However, approaches to integrate such magnetic particles based capture with micro and nanofluidic based assays are still lacking. In this report, we demonstrate a magnetophoretic-based approach for target-specific DNA extraction and concentration within a microfluidic device. This device features a large chamber for reducing flow velocity and an array of MU-magnets for enhancing magnetic flux density. With this strategy, the device is able to collect up to 95 % of the magnetic particles from the fluidic flow and to concentrate these magnetic particles in a collection region. Then an enzymatic reaction is used to detach the DNA from the magnetic particles within the microfluidic device, making the DNA available for subsequent analysis. Concentrations of over 1000-fold for 90 bp dsDNA molecules is demonstrated. This strategy can bridge the gap between detection of low concentration analytes from clinical samples and a range of micro and nanofluidic sensors and devices including nanopores, nano-cantilevers, and nanowires. PMID- 26899966 TI - Single step neutravidin patterning: a lithographic approach for patterning proteins. AB - Protein patterning on surfaces is studied extensively for its potential use in proteomic, nanostructures, drug delivery and sensing. Patterning of proteins at micro and nano scales is especially important not only to understand the function of patterned protein but also to study its interaction with subsequent layers of bio-molecules/cells. Micro scale protein patterning is especially difficult due to the fragile nature of proteins. The already available methods either involve complex chemistries or are specific to a few proteins. Thus, in this regard, a versatile approach to pattern proteins using neutravidin is developed. With this approach of lithography and subsequent lift-off of the photoresist, any biotinylated moiety can be patterned at micron scale resolution. Functionality of patterned neutravidin is confirmed by showing binding of biotinylated polystyrene beads and biotinylated antibodies. In addition, stronger physisorption of neutravidin on bare glass surface, as a result of acetone lift-off, helps sustain the protein layers onto the glass surface without the need of chemical immobilization. PMID- 26899967 TI - Spontaneous (Autoimmune) Chronic Urticaria in Children: Current Evidences, Diagnostic Pitfalls and Therapeutic Management. AB - BACKGROUND: Etiologic diagnosis of pediatric chronic urticaria is quite challenging, as few cases can be associated to specific triggers. Thus, more than 50% of chronic urticaria in children are labeled as idiopathic. Several evidences supported an autoimmune pathogenesis in 30-40% of patients with idiopathic (or spontaneous) chronic urticaria in adults, where the diagnosis of autoimmune chronic urticaria included in vivo and in vitro tests, revealing the presence of autoantibodies against high-affinity IgE receptors mainly. OBJECTIVE: This review aimed at collecting and analyzing all the available evidences on the diagnosis and treatment of autoimmune chronic urticaria in children, including most recent developments and patents. RESULTS AND CONCLUSION: Most pediatric studies relied on autologous serum skin test only, in order to evidence autoimmune urticaria. A complete diagnostic assessment of pediatric autoimmune chronic urticaria, demonstrating an antibodymediated mechanism of disease, might ameliorate the therapeutic management of spontaneous (autoimmune) chronic urticaria in children, supporting the use of omalizumab rather than immuno-suppressive therapy in cases resistant to the firstline treatments. PMID- 26899968 TI - A novel analytical ultracentrifugation based approach to the low resolution structure of gum arabic. AB - Under investigation are the structural properties of gum arabic, an industrially important biopolymer for use as a stabilizer or in drug delivery, using Analytical Ultracentrifugation-a well-established, matrix-free probe for macromolecular size and shape. These results are combined with chromatographically-coupled methods (multi-angle light scattering, differential press imbalance viscometry) to provide a global analysis of its structure in varying ionic strength conditions. This analysis indicates that gum Arabic may have a compact, elliptical structure in solution, the significance of which for biotechnological use is indicated. This modelling method can be applied to other biopolymers and synthetic polymers. (c) 2016 Wiley Periodicals, Inc. Biopolymers 105: 618-625, 2016. PMID- 26899970 TI - Skin glomic tumors referred for local pain and cured by surgical removal. AB - BACKGROUND: Under the definition "glomus tumors" are often erroneously enclosed neoplasms that are absolutely unlike for origin, location, and behavior. Glomus tumors (GTs) are small but extremely painful skin tumors of mesenchymal origin. GTs derive from the neuromyoarterial glomus in adults of middle-age and are generally benign. Due to their small size, diagnosis is often difficult and patients harboring these tumors usually consult many physicians, including sometimes neurosurgeons. More familiar to neurosurgeons are neoplasms as glomus jugular, glomus vagale, and glomus tympanicum that instead all belong to the family of paragangliomas (PGs) and for this reason should not be confused with the aforementioned skin tumors. METHOD AND RESULTS: Here we present a brief review of these two different classes of tumors and also the clarification of any misunderstanding that may derive from an improper use of the terminology. In order to illustrate why skin tumors may interest neurosurgeons, we have reviewed our institutional series of outpatient surgical procedures. Differential diagnosis with other tumors that appear as cutaneous nodules is also discussed. From January 2012 to May 2015, seven patients harboring a GT (six male and one female) were treated. The age ranged from 34 to 71 years (mean, 54.1). The clinical suspect of GT, was validated by ultrasound (US) and, if necessary, by magnetic resonance imaging (MRI). All patients underwent surgery for total tumor removal. Immediate pain relief was obtained in all the patients, and no recurrences were observed during follow-up. Histology confirmed the diagnosis of GT. CONCLUSIONS: Subcutaneous painful nodules, originating from the glomus body, are properly called GTs. Unlikely from other tumors, as schwannomas or neurofibromas, GTs are the cause of pain that is disproportionate to their tiny size and that is not associated to neurological disturbances. Surgical treatment allows a complete regression of pain with significant patient satisfaction. Neoplasms originating from neuroepithelial cells, on the contrary, should not be defined as GTs. PMID- 26899971 TI - Clinicopathologic and neuroradiologic studies of papillary glioneuronal tumors. AB - BACKGROUND: Papillary glioneuronal tumor (PGNT) is a rare, recently described distinct low-grade brain neoplasm. This study was performed to characterize the clinicopathologic and neuroradiologic features of PGNTs. METHODS: We reviewed the medical records of 16 patients with PGNT who underwent surgery, including 11 males and five females (median age 27 years). The clinical, neuroradiologic, histopathologic, and immunohistochemical findings were documented. RESULTS: Headache was the principal presentation. Neuroimaging showed contrast-enhancing, cystic-solid or cystic masses with a mural nodule, mostly involved the frontal or parietal lobes. Histologically, the tumors were characterized by glial fibrillary acidic protein (GFAP)-positive small cuboidal cells lining hyalinized vascular pseudopapillae and synaptophysin and/or NeuN-positive interpapillary neuronal elements. Other findings included small angiomatous areas in ten, small islands of neuropil and rosettes in seven, and microvascular proliferation and/or nuclear atypia in six. Mitoses or necrosis were absent. All lacked isocitrate dehydrogenase 1 (IDH1) R132H protein expression. Low expression of p53 was observed in three cases. Ki67 labeling index ranged from less than 1 to 3 %. All but one was totally resected. Median follow-up was 65 months, and one patient had tumor recurrence. CONCLUSIONS: PGNTs display distinct clinicopathologic and imaging characteristics and indicate a favorable prognosis. However, recurrences sometimes occur. Immunohistochemistry facilitates the appropriate diagnosis of these tumors. Complete resection of the tumor is important for a favorable outcome. PMID- 26899969 TI - Developmental anomalies of the distal vertebral artery and posterior inferior cerebellar artery: diagnosis by CT angiography and literature review. AB - PURPOSE: The aim of this study was to identify variations in the anatomy of the distal vertebral artery (VA) and posterior inferior cerebellar artery (PICA) with computed tomography (CT) angiography. METHODS: CT angiography was performed at two hospitals. And the results were analyzed for VA anomalies. RESULTS: Seven of the 3067 patients who received brain CT angiography in first hospital had seven intracranial VA fenestrations. Twelve of 546 patients who received CT angiography of intracranial and extracranial vessels in second hospital had 16 anatomical variations of the V3 segment. Two fenestrations of the V3 segment, three C1 origins of the PICA, seven aberrant VAs with an intradural course at the C2 level without a normal VA, and four aberrant VAs with an intradural course at the C2 level with a normal VA were observed. Seventeen of the 314 patients who received cervical CT angiography in second hospital had 21 anatomical variations of the VA. Two fenestrations of the V3 segment, six C1 origins of the PICA, three C2 origins of the PICA, one VA origin of the occipital artery, one fenestration of the V4 segment, five aberrant VAs with an intradural course at the C2 level without a normal VA, and three aberrant VAs with an intradural course at the C2 level with a normal VA were observed. CONCLUSIONS: A certain number of anatomical variants of the distal VA and PICA may reflect variations in size and connections of the lateral or posterior spinal artery. PMID- 26899972 TI - Melatonin, but not melatonin receptor agonists Neu-P11 and Neu-P67, attenuates TNBS-induced colitis in mice. AB - Melatonin is known as a strong antioxidant and possesses anti-inflammatory properties. Recently, melatonin was shown to improve colitis in animal models of inflammatory bowel diseases. The aim of the present study was to characterize the role of melatonin receptors (MT) in the anti-inflammatory effect of melatonin and to assess the anti-inflammatory potential of two novel MT receptor agonists, Neu P11 and Neu-P67, in the mouse model of trinitrobenzenesulfonic acid (TNBS) induced colitis. Colitis was induced on day 1 by intracolonic (i.c.) administration of TNBS in 30 % ethanol in saline. Melatonin (4 mg/kg, per os (p.o.)), Neu-P11 (20 mg/kg, p.o.; 50 mg/kg, intraperitoneally (i.p.), 50 mg/kg, i.c.), and Neu-P67 (20 mg/kg, p.o.) were given twice daily for 3 days. Luzindole (5 mg/kg, i.p.) was injected 15 min prior to melatonin administration. On day 4, macroscopic and microscopic damage scores were assessed and myeloperoxidase (MPO) activity quantified using O-dianisidine-based assay. Melatonin significantly attenuated colitis in mice, as indicated by the macroscopic score (1.90 +/- 0.34 vs. 3.82 +/- 0.62 for melatonin- and TNBS-treated mice, respectively), ulcer score (0.87 +/- 0.18 vs. 1.31 +/- 0.19, respectively), and MPO activity (4.68 +/- 0.70 vs.6.26 +/- 0.94, respectively). Luzindole, a MT receptor antagonist, did not inhibit the anti-inflammatory effect of melatonin (macroscopic score 1.12 +/- 0.22, ulcer score 0.50 +/- 0.16); however, luzindole increased MPO activity (7.57 +/- 1.05). MT receptor agonists Neu-P11 and Neu-P67 did not improve inflammation induced by TNBS. Melatonin, but not MT receptor agonists, exerts potent anti inflammatory action in acute TNBS-induced colitis. Our data suggests that melatonin attenuates colitis by additional, MT receptor-independent pathways. PMID- 26899973 TI - Electrospun formulations of acyclovir, ciprofloxacin and cyanocobalamin for ocular drug delivery. AB - Two series of fibers containing the active ingredients acyclovir, ciprofloxacin and cyanocobalamin, and combinations of these drugs, were prepared by electrospinning. One set used the hydrophilic poly(vinylpyrrolidone) (PVP) as the filament-forming polymer, while the other used the slow-dissolving poly(epsilon caprolactone) (PCL). The fibers were found to have cylindrical morphologies, although there was evidence for solvent occlusion with the PVP systems and for some drug particles in the PCL materials. The active ingredients were generally present in the amorphous physical form in the case of PVP, but evidence of crystallinity was observed with PCL. The existence of intermolecular interactions between the drugs and polymers was proven using simple molecular modeling calculations. Drug release from the various fibers was tested in a validated in vitro outflow model of the eye, and the fiber formulations found to be capable of extending drug release. We thus conclude that electrospun matrices such as those prepared in this work have potential for use as intravitreal implants. PMID- 26899974 TI - Prediction and characterization of P-glycoprotein substrates potentially bound to different sites by emerging chemical pattern and hierarchical cluster analysis. AB - P-glycoprotein (P-gp), an ATP-binding cassette (ABC) multidrug transporter, can actively transport a broad spectrum of chemically diverse substrates out of cells and is heavily involved in multidrug resistance (MDR) in tumors. So far, the multiple specific binding sites remain a major obstacle in developing an efficient prediction method for P-gp substrates. Herein, emerging chemical pattern (ECP) combined by hierarchical cluster analysis was utilized to predict P gp substrates as well as their potential binding sites. An optimal ECP model using only 3 descriptors was established with prediction accuracies of 0.80, 0.81 and 0.74 for 803 training samples, 120 test samples, and 179 independent validation samples, respectively. Hierarchical cluster analysis (HCA) of the ECPs of P-gp substrates derived 2 distinct ECP groups (ECPGs). Interestingly, HCA of the P-gp substrates based on ECP similarities also showed 2 distinct classes, which happened to be dominated by the 2 ECPGs, respectively. In the light of available experimental proofs and molecular docking results, the 2 distinct ECPGs were proved to be closely related to the binding profiles of R- and H-site substrates, respectively. The present study demonstrates, for the first time, a successful ECP model, which can not only accurately predict P-gp substrates, but also identify their potential substrate-binding sites. PMID- 26899975 TI - Sustained release of risperidone from biodegradable microspheres prepared by in situ suspension-evaporation process. AB - Risperidone-loaded poly (D,L-lactide-co-glycolide) (PLGA) microspheres were prepared with a suspension-evaporation process with an aqueous suspension containing an in situ-formed aluminum hydroxide inorganic gel (SEP-AL process) and evaluated for encapsulation efficiency, particle size, surface morphology, glass transition temperature, in vitro drug release profile, and in vivo behavior. The SEP-AL microspheres were compared with conventional oil-in-water (O/W) emulsion solvent evaporation method using polyvinylalcohol (PVA) as an emulsifier (CP-PVA process). The microspheres were spherical in shape. DSC measurements showed that risperidone crystallinity was greatly reduced due to the homogeneous distribution of risperidone in PLGA microspheres. In vitro drug release profile from the microspheres showed a sigmoidal pattern of negligible initial burst up to 24h and minimal release (time-lag) for 7 days. After the lag phase, slow release took a place up to 25 days and then rapid release occurred sharply for 1 week. In vivo rat pharmacokinetic profile from the microspheres showed very low blood concentration level at the initial phase (up to 24h) followed by the latent phase up to 21 days. At the 3rd week, main phase started and the blood concentration of the drug increased up to the 5th week, and then gradually decreased. The risperidone-loaded PLGA microspheres produced by SEP-AL process showed excellent controlled release characteristics for the effective treatment of schizophrenia patients. PMID- 26899977 TI - In situ gelling systems based on Pluronic F127/Pluronic F68 formulations for ocular drug delivery. AB - This study evaluated the use of Pluronic F127 and Pluronic F68 as excipients for formulating in situ gelling systems for ocular drug delivery. Thermal transitions have been studied in aqueous solutions of Pluronic F127, Pluronic F68 as well as their binary mixtures using differential scanning calorimetry, rheological measurements, and dynamic light scattering. It was established that the formation of transparent gels at physiologically relevant temperatures is observed only in the case of 20 wt% of Pluronic F127. The addition of Pluronic F68 to Pluronic F127 solutions increases the gelation temperature of binary formulation to above physiological range of temperatures. The biocompatibility evaluation of these formulations using slug mucosa irritation assay and bovine corneal erosion studies revealed that these polymers and their combinations do not cause significant irritation. In vitro drug retention study on glass surfaces and freshly excised bovine cornea showed superior performance of 20 wt% Pluronic F127 compared to other formulations. In addition, in vivo studies in rabbits demonstrated better retention performance of 20 wt% Pluronic F127 compared to Pluronic F68. These results confirmed that 20 wt% Pluronic F127 offers an attractive ocular formulation that can form a transparent gel in situ under physiological conditions with minimal irritation. PMID- 26899978 TI - Novel polymeric nanoparticles targeting the lipopolysaccharides of Pseudomonas aeruginosa. AB - Considering outburst of various infectious diseases globally, nanoparticle assisted targeted drug delivery has emerged as a promising strategy that can enhance the therapeutic efficacy and minimize the undesirable side effects of an antimicrobial agents. Molecular imprinting is a newly developed strategy that can synthesize a drug carrier with highly stable ligand-like 'cavity', may serve as a new platform of ligand-free targeted drug delivery systems. In this study, we use the amphiphilic lipopolysaccharides, derived from Pseudomonas aeruginosa as imprinting template and obtained an evenly distributed sub-40 nm polymeric nanoparticles by using inverse emulsion method. These molecularly imprinted nanoparticles (MIPNPs) showed specific binding to the lipopolysaccharide as determined by fluorescence polarization and microscale thermophoresis. MIPNPs showed selective recognition of target bacteria as detected by flow cytometry. Additionally, MIPNPs exhibited the in vivo targeting capabilities in both the keratitis model and meningitis model. Moreover, the photosensitizer methylene blue-loaded MIPNPs presented significantly strong inhibition of bacterial Growth, compared to non-imprinted controls for in vitro model of the photodynamic therapy. Our study shows an attempt to design a magic bullet by molecular imprinting that may provide a novel approach to generate synthetic carrier for targeting pathogen and treatment for a variety of infectious human diseases. PMID- 26899976 TI - Lipid-based nanoformulations for peptide delivery. AB - Nanoformulations have attracted a lot of attention because of their size dependent properties. Among the array of nanoformulations, lipid nanoformulations (LNFs) have evoked increasing interest because of the advantages of their high degree of biocompatibility and versatility. The performance of lipid nanoformulations is greatly influenced by their composition and structure. Therapeutic peptides represent a growing share of the pharmaceutical market. However, the main challenge for their development into commercial products is their inherent physicochemical and biological instability. Important peptides such as insulin, calcitonin and cyclosporin A have been incorporated into LNFs. The association or encapsulation of peptides within lipid-based carriers has shown to protect the labile molecules against enzymatic degradation. This review describes strategies used for the formulation of peptides and some methods used for the assessment of association efficiency. The advantages and drawbacks of such carriers are also described. PMID- 26899979 TI - Preparation and characterization of fast dissolving flurbiprofen and esomeprazole solid dispersion using spray drying technique. AB - We aimed to develop an immediate-release flurbiprofen (FLU) and esomeprazole (ESO) combination formulation with enhanced gastric aqueous solubility and dissolution rate. Aqueous solubility can be enhanced by formulating solid dispersions (SDs) with a polyvinylpyrrolidone (PVP)-K30 hydrophilic carrier, using spray-drying technique. Aqueous and gastric pH dissolution can be achieved by macro-environmental pH modulation using sodium bicarbonate (NaHCO3) and magnesium hydroxide (Mg(OH)2) as the alkaline buffer. FLU/ESO-loaded SDs (FLU/ESO SDs) significantly improved aqueous solubility of both drugs, compared to each drug powder. Dissolution studies in gastric pH and water were compared with the microenvironmental pH modulated formulations. The optimized FLU/ESO-SD powder formulation consisted of FLU/ESO/PVP-K30/sodium carbonate (Na2CO3) in a weight ratio 1:0.22:1.5:0.3, filled in the inner capsule. The outer capsule consisted of NaHCO3 and Mg(OH)2, which created the macro-environmental pH modulation. Increased aqueous and gastric pH dissolution of FLU and ESO from the SD was attributed to the alkaline buffer effects and most importantly, to drug transformation from crystalline to amorphous SD powder, clearly revealed by scanning electron microscopy, differential scanning calorimetry, and powder X-ray diffraction studies. Thus, the combined FLU and ESO SD powder can be effectively delivered as an immediate-release formulation using the macro-environmental pH modulation concept. PMID- 26899980 TI - Tumor targeted delivery of octreotide-periplogenin conjugate: Synthesis, in vitro and in vivo evaluation. AB - Periplogenin (PPG), a cardiac glycoside prepared from Cortex periplocae, with similar structure to bufalin, has been found to induce apoptosis in many tumor cells. However, lots of cardiac glycosides possessing strong antitumor activity in vitro have still not passed phase I clinical trials, mostly due to poor tumor selectivity and systemic toxicity. To overcome this drawback, we designed octreotide-periplogenin (OCT-PPG) conjugate by coupling PPG-succinate to the amino-terminal end of octreotide. In comparison with free PPG, the conjugate exhibited significantly stronger cytotoxicity on HepG2 cells (SSTRs overexpression) but much less toxicity in L-02 cells. After intravenous injection of OCT-PPG conjugate into H22 tumor-bearing mice, its total accumulation in tumor was 2.3 fold higher than that of free PPG, but was 0.71- and 0.84-fold lower in heart and liver, respectively, suggesting somatostatin-mediated target delivery of PPG into the tumor tissue and reduced distribution in heart and liver. In vivo studies using H22 tumor model in mice confirmed the remarkable therapeutic effect of this conjugate. These results suggested that OCT-PPG conjugate could provide a new approach for clinical application of cardiac glycosides and as a targeting agent for cancer therapy. PMID- 26899981 TI - Statistical tools and control of internal lubricant content of inhalation grade HPMC capsules during manufacture. AB - The internal lubricant content (ILC) of inhalation grade HPMC capsules is a key factor to ensure good powder release when the patient inhales a medicine from a dry powder inhaler (DPI). Powder release from capsules has been shown to be influenced by the ILC. The characteristics used to measure this are the emitted dose, fine particle fraction and mass median aerodynamic diameter. In addition the ILC level is critical for capsule shell manufacture because it is an essential part of the process that cannot work without it. An experiment has been applied to the manufacture of inhalation capsules with the required ILC. A full factorial model was used to identify the controlling factors and from this a linear model has been proposed to improve control of the process. PMID- 26899982 TI - Plasmablastic lymphoma involving the stomach in an HIV positive man. PMID- 26899984 TI - Secondary conditions in a community sample of people with spinal cord damage. AB - OBJECTIVE: To compare secondary conditions in people with traumatic spinal cord injury (SCI) and non-traumatic spinal cord dysfunction (SCDys). DESIGN: Survey; completed August 2012 - June 2013. SETTING: Community, Australia. PARTICIPANTS: Adults with spinal cord damage from any cause. INTERVENTIONS: Nil. OUTCOME MEASURES: Demographic and clinical variables and the SCI-Secondary Conditions Scale (SCI-SCS). RESULTS: Survey completed by 150 people: 112 (74.7%) with traumatic SCI and 38 (25.3%) with non-traumatic SCDys a median of 10 years post onset. No significant difference (t = -0.6, P = 0.6) in the total SCI-SCS score between those with SCI (mean 13.7) and SCDys (mean 14.4). Except for bladder problems (SCDys mean = 1.5, SD = 1.1; SCI mean = 1.0, SD=1.1; t = -2.6, P = 0.01) there were no significant differences between the aetiology groups regarding the conditions comprising the SCI-SCS (all other P values >0.1). The most common significant or chronic problems from the SCI-SCS were: sexual problems 41%; chronic pain 24%; bladder dysfunction 17%; spasms 17%; joint and muscle pain 15%; bowel dysfunction 14%; circulation problems 14%; contractures 9%; urinary tract infections 9%; pressure ulcer 7% and postural hypotension 5%. A linear regression analysis found that tetraplegia and higher disability were the only variables that significantly influenced (R2 = 0.13; P = 0.005) the total SCI-SCS score and that sex, age, years post injury and etiology of spinal cord damage had no influence. CONCLUSIONS: Secondary conditions following spinal cord damage do not appear to be influenced by etiology. Prevention and management of secondary conditions following need to consider people with non-traumatic SCDys as well as those with traumatic SCI. PMID- 26899983 TI - Commentary to "Detailed evaluation of the upper urinary tract in patients with prune belly syndrome using magnetic resonance urography". PMID- 26899986 TI - The design of a bipodal bis(pentafluorophenoxy)aluminate supported on silica as an activator for ethylene polymerization using surface organometallic chemistry. AB - A new class of well-defined activating supports for olefin polymerization was obtained via the surface organometallic chemistry approach. High activities in slurry polymerization of ethylene along with industrial-grade physical properties of the resulting polyethylene were obtained when these activators were combined with metallocene complexes in the presence of triisobutylaluminium. PMID- 26899985 TI - Towards a better spatial quantification of nitrogen deposition: A case study for Czech forests. AB - The quantification of atmospheric deposition flux is essential for assessment of its impact on ecosystems. We present an advanced approach for the estimation of the spatial pattern of atmospheric nitrogen deposition flux over the Czech forests, collating all available measured data and model results. The aim of the presented study is to provide an improved, more complete, more reliable and more realistic estimate of the spatial pattern of nitrogen deposition flux over one country. This has so far usually been based on measurements of ambient NOx concentrations as dry deposition proxy, and [Formula: see text] and [Formula: see text] in precipitation as wet deposition proxy. For estimation of unmeasured species contributing to dry deposition, we used the CAMx Eulerian photochemical dispersion model, coupled with the Aladin regional numeric weather prediction model. The contribution of fog and dissolved organic nitrogen was estimated using a geostatistical data driven model. We prepared individual maps for particular components applying the most relevant approach and then merged all layers to obtain a final map representing the best estimate of nitrogen deposition over the Czech Republic. Final maps accounting for unmeasured species clearly indicate that the approach used so far may result in a substantial underestimation of nitrogen deposition flux. Our results showed that nitrogen deposition over the Czech forested area in 2008 was well above 2 g N m(-2) yr(-1), with almost 70% of forested area receiving 3-4 g N m(-2) yr(-1). NH3 and gaseous HNO3, contributing about 80%, dominated the dry nitrogen deposition. Estimating the unmeasured nitrogen species by modeled values provides realistic approximations of total nitrogen deposition that also result in more realistic spatial patterns that could be used as input for further studies of likely nitrogen impacts on ecosystems. PMID- 26899987 TI - Differential Effects of Antiepileptic Drugs on Focal Seizures in the Intrahippocampal Kainate Mouse Model of Mesial Temporal Lobe Epilepsy. AB - AIMS: Mesial temporal lobe epilepsy (MTLE) is the most common form of drug refractory epilepsy. Most of the morphological and electrophysiological features of human MTLE can be reproduced in a mouse by a unilateral intrahippocampal injection of kainate (MTLE mouse model). The effects of antiepileptic drugs (AEDs) on the occurrence of recurrent focal hippocampal seizures in this model remain to be specified. Here, we addressed the pharmacological reactivity of this model to the most commonly used AEDs. METHODS: Using depth electroencephalographical (EEG) recordings, we tested the dose-response effects of acute injection of nine AEDs on the occurrence of hippocampal paroxysmal discharges (HPDs) as well as on ictal and interictal power spectra in the MTLE mouse model. RESULTS: Valproate, carbamazepine, and lamotrigine dose dependently suppressed HPDs and modified the general behavior and/or EEG activity. Levetiracetam and pregabalin suppressed HPDs at high doses but without any behavioral nor interictal EEG changes. Finally, phenobarbital, tiagabine, vigabatrin, and diazepam suppressed HPDs in a dose-dependent manner at doses devoid of obvious behavioral effects. CONCLUSION: The MTLE mouse model displays a differential sensitivity to AEDs with a greater efficacy of drug that facilitates GABAergic transmission. This model provides an efficient tool to identify new treatment for drug-resistant forms of focal epilepsies. PMID- 26899988 TI - Body shape transformation along a shared axis of anatomical evolution in labyrinth fishes (Anabantoidei). AB - Major morphological transformations, such as the evolution of elongate body shape in vertebrates, punctuate evolutionary history. A fundamental step in understanding the processes that give rise to such transformations is identification of the underlying anatomical changes. But as we demonstrate in this study, important insights can also be gained by comparing these changes to those that occur in ancestral and closely related lineages. In labyrinth fishes (Anabantoidei), rapid evolution of a highly derived torpedo-shaped body in the common ancestor of the pikehead (Luciocephalus aura and L. pulcher) occurred primarily through exceptional elongation of the head, with secondary contributions involving reduction in body depth and lengthening of the precaudal vertebral region. This combination of changes aligns closely with the primary axis of anatomical diversification in other anabantoids, revealing that pikehead evolution involved extraordinarily rapid change in structures that were ancestrally labile. Finer-scale examination of the anatomical components that determine head elongation also shows alignment between the pikehead evolutionary trajectory and the primary axis of cranial diversification in anabantoids, with much higher evolutionary rates leading to the pikehead. Altogether, our results show major morphological transformation stemming from extreme change along a shared morphological axis in labyrinth fishes. PMID- 26899989 TI - Differential Odour Coding of Isotopomers in the Honeybee Brain. AB - The shape recognition model of olfaction maintains that odorant reception probes physicochemical properties such as size, shape, electric charge, and hydrophobicity of the ligand. Recently, insects were shown to distinguish common from deuterated isotopomers of the same odorant, suggesting the involvement of other molecular properties to odorant reception. Via two-photon functional microscopy we investigated how common and deuterated isoforms of natural odorants are coded within the honeybee brain. Our results provide evidence that (i) different isotopomers generate different neuronal activation maps, (ii) isotopomer sensitivity is a general mechanism common to multiple odorant receptors, and (iii) isotopomer specificity is highly consistent across individuals. This indicates that honeybee's olfactory system discriminates between isotopomers of the same odorant, suggesting that other features, such as molecular vibrations, may contribute to odour signal transduction. PMID- 26899990 TI - An unusual adverse reaction to iodine-based contrast agent. PMID- 26899991 TI - Kounis syndrome: Aspects on pathophysiology and management. PMID- 26899992 TI - The modulating role of ADRA2B in emotional working memory: Attending the negative but remembering the positive. AB - Previous studies found that the ADRA2B gene modulates early perception and attention. Here, we aimed to examine whether ADRA2B polymorphisms also influence emotional working memory and the willingness to implement behaviors (switching affective intonation) in order to avoid negative information, both considered indexes of cognitive-affective flexibility. We examined genotype data collected from 212 healthy females, 91 ADRA2B carriers and 121 non-carriers, and found that carriers showed a positivity bias in working memory. That is, carriers remembered a higher number of positive words compared to negative and neutral words. In addition, although carriers were more unwilling to switch intonation in order to avoid negative information, they showed better recognition memory for words read with a positive intonation. These findings suggest that deletion variants of ADRA2B may show greater levels of cognitive-affective flexibility compared to non carriers. PMID- 26899993 TI - Concurrent assessment of memory for object and place: Evidence for different preferential importance of perirhinal cortex and hippocampus and for promnestic effect of a neurokinin-3 R agonist. AB - We here explore the utility of a paradigm that allows the simultaneous assessment of memory for object (what) and object location (where) and their comparative predominance. Two identical objects are presented during a familiarity trial; during the test trial one of these is displaced, and a new object is presented in a familiar location. When tested 5 or 80min later, rats explored both the novel and the displaced objects more than two familiar stationary objects, indicating intact memory for both, object and place. When tested 24h later rats explored the novel object more than the displaced familiar one, suggesting that forgetting differently influenced object and place memory, with memory for object being more robust than memory for place. Animals that received post-trial administration of the neurokinin-3 receptor agonist senktide and were tested 24h later, now explored the novel and displaced objects equally, suggesting that the treatment prevented the selective decay of memory for location. Next, animals received NMDA lesions in either the perirhinal cortex or the hippocampus, which are hypothesized to be preferentially involved in memory for objects and memory for place, respectively. When tested 5 or 80min later, the perirhinal cortex lesion group explored the displaced object more, indicating relatively deficient object memory, while the hippocampal lesion led to the opposite pattern, demonstrating comparatively deficient place memory. These results suggest different preferential engagement of the perirhinal cortex and hippocampus in their processing of memory for object and place. This preference test lends itself to application in the comparison of selective lesions of neural sites and projection systems as well as to the assessment of possible preferential action of pharmacological agents on neurochemical processes that subserve object vs place learning. PMID- 26899995 TI - Simultaneous magnetic resonance imaging and pharmacokinetic analysis of intramuscular depots. AB - The present pilot study introduces a method that might give novel insights in drug absorption processes from intramuscularly administered depots. An oily suspension or an aqueous solution of paracetamol (6 mg/kg body mass), prednisolone or its hemisuccinate sodium salt for the aqueous solutions (10mg/kg body mass) or diclofenac (10mg/kg body mass) was injected into the muscle tissue of the hind leg of female Lewis-rats (n=47). For the oily suspensions the micronized particles were suspended in medium-chain triglycerides. The aqueous solutions were buffered to a pH of 7.4 +/- 0.5. Polyethylene glycol was added as a cosolvent in the formulations containing paracetamol (acetaminophen) and diclofenac and sodium chloride was added to the aqueous solutions of prednisolone hemisuccinate sodium to achieve nearly isotonic formulations. The formed depot was visualized by magnetic resonance imaging (MRI) and characterized with regard to volume and surface area. A 7 T-small animal scanner was used and T1-weighted and T2-weighted sequences including a fat saturation were performed. Simultaneously blood samples were taken and the drugs were quantitatively analyzed. The water based solvent and the oily dispersion agent were visible in the MRI images without the use of contrast agents. Since a free hand injection mostly led to an application directly into the fascia, resulting in a fast removal of the depot, MRI-guided injection was conducted. Comparing pharmacokinetic data with MRI data it was observed that maximal blood levels occurred before the solvent and the dispersion agent were removed from the muscle tissue. Thus, the drug is not absorbed together with the depot. Furthermore, no correlation was found between the shape of the depot and the rate of absorption. Consequently, a higher surface area or volume of the depot did not result in a faster release or absorption of the drugs from the tested formulations. In contrast to the paracetamol and prednisolone formulations the formulations containing diclofenac led to a massive accumulation of interstitial fluid around the injection area being a sign for an acute local reaction. Histological analysis of the muscle tissue revealed a clear correspondence between the amount of interstitial fluid and the extent of infiltrating lymphocytes and granulocytes indicating a tissue response. In conclusion combining MRI with pharmacokinetic data is a suitable method to gain deeper insights into drug absorption processes from intramuscular depots. Furthermore, MRI offers a great possibility detecting local side effects caused by an intramuscularly applied dosage form. This might be very useful in preclinical phases during the development of new intramuscular formulations. PMID- 26899994 TI - miR-155 acts as an anti-inflammatory factor in atherosclerosis-associated foam cell formation by repressing calcium-regulated heat stable protein 1. AB - Atherosclerosis (AS) is chronic inflammation in response to lipid accumulation. MicroRNA-155 (miR-155) is being increasingly studied to evaluate its potential as diagnostic biomarkers and therapeutic targets in many diseases. However, delineating the role of miR-155 in AS remains difficult. Here, we detected constitutive expression of several microRNAs (miRNAs) possibly associated with cardiovascular disease in foam cells and clinical specimens from patients with AS. Among them, we found that the level of miR-155 in foam cells was the most significantly elevated in a dose- and time-dependent manner. In addition, the expression of miR-155 was elevated in the plasma and plaque of patients with AS. We also reported for the first time that miR-155 targets calcium-regulated heat stable protein 1 (CARHSP1), which regulates the stability of tumor necrosis factor alpha (TNF-alpha) mRNA. Furthermore, we investigated the mechanism by which the miR-155 level is elevated. miR-155 upregulation is due to transcriptional regulation by nuclear factor (NF)-kappaB, which is activated by the inflammatory factor TNF-alpha. In summary, increased miR-155 relieves chronic inflammation by a negative feedback loop and plays a protective role during atherosclerosis-associated foam cell formation by signaling through the miR-155 CARHSP1-TNF-alpha pathway. PMID- 26899997 TI - Bifurcation-based adiabatic quantum computation with a nonlinear oscillator network. AB - The dynamics of nonlinear systems qualitatively change depending on their parameters, which is called bifurcation. A quantum-mechanical nonlinear oscillator can yield a quantum superposition of two oscillation states, known as a Schrodinger cat state, via quantum adiabatic evolution through its bifurcation point. Here we propose a quantum computer comprising such quantum nonlinear oscillators, instead of quantum bits, to solve hard combinatorial optimization problems. The nonlinear oscillator network finds optimal solutions via quantum adiabatic evolution, where nonlinear terms are increased slowly, in contrast to conventional adiabatic quantum computation or quantum annealing, where quantum fluctuation terms are decreased slowly. As a result of numerical simulations, it is concluded that quantum superposition and quantum fluctuation work effectively to find optimal solutions. It is also notable that the present computer is analogous to neural computers, which are also networks of nonlinear components. Thus, the present scheme will open new possibilities for quantum computation, nonlinear science, and artificial intelligence. PMID- 26899996 TI - GATA3 inhibits GCM1 activity and trophoblast cell invasion. AB - Development of human placenta involves the invasion of trophoblast cells from anchoring villi into the maternal decidua. Placental transcription factor GCM1 regulates trophoblast cell invasion via transcriptional activation of HtrA4 gene, which encodes a serine protease enzyme. The GATA3 transcription factor regulates trophoblast cell differentiation and is highly expressed in invasive murine trophoblast giant cells. The regulation of trophoblastic invasion by GCM1 may involve novel cellular factors. Here we show that GATA3 interacts with GCM1 and inhibits its activity to suppress trophoblastic invasion. Immunohistochemistry demonstrates that GATA3 and GCM1 are coexpressed in villous cytotrophoblast cells, syncytiotrophoblast layer, and extravillous trophoblast cells of human placenta. Interestingly, GATA3 interacts with GCM1, but not the GCM2 homologue, through the DNA-binding domain and first transcriptional activation domain in GCM1 and the transcriptional activation domains and zinc finger 1 domain in GATA3. While GATA3 did not affect DNA-binding activity of GCM1, it suppressed transcriptional activity of GCM1 and therefore HtrA4 promoter activity. Correspondingly, GATA3 knockdown elevated HtrA4 expression in BeWo and JEG-3 trophoblast cell lines and enhanced the invasion activities of both lines. This study uncovered a new GATA3 function in placenta as a negative regulator of GCM1 activity and trophoblastic invasion. PMID- 26899999 TI - [Obstetrical ultrasound simulator as a tool for improving teaching strategies for beginners: Pilot study and review of the literature]. AB - OBJECTIVES: The aim of this study was to evaluate the obstetrical ultrasound simulator as an initiation tool for teaching obstetrical ultrasound scanning for beginners. METHODS: Twenty medical students with no experience in ultrasound scan (US) received a basic theoretical ultrasonography course on US principles and 2nd trimester biometrical measurements. The participants were then divided into 2 groups (A, B). Only group A received a practical 2nd trimester scan training session on the simulator where they were asked to determine fetal and placental position, and to take the 3 biometrical standardized measurements. Group B had the same training session but with a real ultrasound machine and a pregnant volunteer. The 2 groups were then asked to perform an US session on real patients (22 weeks) during which they had to do the same US study. The time needed to complete the whole scan was analyzed. The quality of the measurements was compared based on the previously published Objective Quality Criteria scoring. RESULTS: The mean total score was significantly (P=0.001) better for group A (14.3+/-1.4) compared to group B 10.3 (+/-2.75) for group A and B respectively. The time needed to accomplish the whole exam tended to be longer for group A (569+/-174s) compared to group A (479+/-104s) (P=0.18). CONCLUSIONS: The simulator might be a useful initiation tool to obstetric ultrasound for those who never practiced. It might prove a time sparing procedure in the training process and allow trainees to reach a basic practice level before performing examinations on actual patients. PMID- 26900000 TI - How digital storytelling is used in mental health: A scoping review. AB - The creative arts can be used to support stakeholders of mental health services to communicate and share their lived experience. Digital storytelling is one method that has been used to capture people's lived experience. In this scoping review, we were interested in mapping how digital storytelling has been used in mental health, and to identify gaps in the literature. Nine databases were searched to identify peer reviewed literature published between January 2000 and August 2015; 15 articles were included in the review. The articles were categorized across four broad areas: educational interventions, learning skills, learning about other people's lived experience, and learning about personal lived experience. We identify that while digital storytelling has potential as a participatory process to promote mutual understanding of and empathy towards lived experiences in mental health, there is a dearth of research in this area. More research is needed on the use of digital storytelling in mental health to determine its effectiveness in progressing a recovery orientation in service provision that is built on solidarity and a social justice agenda. PMID- 26899998 TI - Differences in attitude, education, and knowledge about oral anticoagulation therapy among patients with atrial fibrillation in Europe: result of a self assessment patient survey conducted by the European Heart Rhythm Association. AB - The purpose of this patient survey was to analyse the knowledge about blood thinning medications relative to gender, age, education, and region of residence in patients with atrial fibrillation (AF). A total of 1147 patients with AF [mean age 66 +/- 13 years, 529 (45%) women] from eight European countries responded to this survey. Most patients understood that the indication for anticoagulation therapy was to 'thin the blood', but 8.1% responded that the purpose of the medication was to treat the arrhythmia. Patients with college or university grades reported less frequent deviations from their target INR range compared with those without schooling (2.8% vs. 5.1%, P < 0.05). The awareness of anticoagulation-related risk of bleedings was lowest in patients without schooling (38.5%) and highest in those with college and university education (57.0%), P < 0.05. The same pattern was also observed regarding patient's awareness of non-vitamin K antagonist oral anticoagulants (NOACs): 56.5% of the patients with university education and only 20.5% of those without schooling (P < 0.05) knew about NOACs, indicating that information about new anticoagulation therapies remains well below the target. Bleeding events were statistically less frequent in patients on NOACs compared with vitamin K antagonists. The education level and patients' knowledge have a direct influence on the global management of the anticoagulation. PMID- 26900001 TI - [Solitary papule above the right eyebrow in patient with chronic lymphocytic leukemia: Importance of early diagnosis]. PMID- 26900002 TI - A six-month Serratia marcescens outbreak in a Neonatal Intensive Care Unit. AB - OBJECTIVE: To investigate a Serratia marcescens (S. marcescens) outbreak in a Neonatal Unit in a tertiary university hospital. METHODS: Descriptive study of children admitted to the Unit with S. marcescens infection from November 2012 to March 2013. Conventional microbiological methods for clinical and environmental samples were used. The clonal relationship between all available isolates was established by molecular methods. A multidisciplinary team was formed, and preventive measures were taken. RESULTS: S. marcescens was isolated from 18 children. The overall attack rate was 12%, and the case fatality rate in the Intensive Care Unit was 23.5%. The most prevalent types of infections were pneumonia (6), conjunctivitis (6), and bloodstream infection (5). Clinical isolates and environmental isolates obtained from an incubator belonged to a unique clone. The clonal relationship between all S. marcescens strains helped us to identify the possible source of the outbreak. CONCLUSION: Isolation of S. marcescens from stored water in a container, and from the surface of an incubator after cleaning, suggests a possible environmental source as the outbreak origin, which has been perpetuated due to a failure of cleaning methods in the Unit. The strict hygiene and cleaning measures were the main factors that contributed to the end of the outbreak. PMID- 26900004 TI - Acute effects of different inspiratory efforts on ventilatory pattern and chest wall compartmental distribution in elderly women. AB - It is not completely described how aging affect ventilatory kinematics and what are the mechanisms adopted by the elderly population to overcome these structural modifications. Given this, the aim was to evaluate the acute effects of different inspiratory efforts on ventilatory pattern and chest wall compartmental distribution in elderly women. Variables assessed included: tidal volume (Vt), total chest wall volume (Vcw), pulmonary rib cage (Vrcp%), abdominal rib cage (Vrca%) and abdominal compartment (Vab%) relative contributions to tidal volume. These variables were assessed during quiet breathing, maximal inspiratory pressure maneuver (MIP), and moderate inspiratory resistance (MIR; i.e., 40% of MIP). 22 young women (age: 23.9 +/- 2.5 years) and 22 elderly women (age: 68.2 +/ 5.0 years) participated to this study. It was possible to show that during quiet breathing, Vab% was predominant in elderly (p<0.001), in young, however, Vab% was similar to Vrcp% (p=0.095). During MIR, Vrcp% was predominant in young (p<0.001) and comparable to Vab% in elderly (p=0.249). When MIP was imposed, both groups presented a predominance of Vrcp%. In conclusion, there are differences in abdominal kinematics between young and elderly women during different inspiratory efforts. In elderly, during moderate inspiratory resistance, the pattern is beneficial, deep, and slow. Although, during maximal inspiratory resistance, the ventilatory pattern seems to predict imminent muscle fatigue. PMID- 26900003 TI - Neuroanatomical and physiological evidence that the retrotrapezoid nucleus/parafacial region regulates expiration in adult rats. AB - The rostroventrolateral medulla contains two functional neuronal populations: (1) the parafacial respiratory group (pFRG) neurons and (2) the chemosensitive retrotrapezoid nucleus (RTN) neurons. Using anatomical and physiological techniques, we investigated the role of the RTN/pFRG in CO2-induced active expiration (AE) in urethane-anesthetized rats. Anterograde tracing using biotinylated dextran amine (BDA) revealed dense neuronal projections emanating from the RTN/pFRG to the caudal ventral respiratory group (cVRG), 60% of which contained vesicular glutamate transporter-2. The minority (16%) of the RTN projections to the cVRG emanated from Phox2b positive neurons. Hypercapnia (10% CO2) increased DiaEMG and elicited AbdEMG activity. Bilateral injections of muscimol (2mM) into the RTN/pFRG reduced the activation of DiaEMG (23+/-4%) and abolished AE-induced by chemoreflex stimulation. Taken together, these results support the presence of direct excitatory projections from RTN/pFRG neurons to cVRG expiratory premotor neurons, playing a role in the generation/modulation of AE. PMID- 26900005 TI - Biomedical Potential of mTOR Modulation by Nanoparticles. AB - Modulation of the mammalian target of rapamycin (mTOR), the principal regulator of cellular homeostasis, underlies the biological effects of engineered nanoparticles, including regulation of cell death/survival and metabolic responses. Understanding the mechanisms and biological actions of nanoparticle mediated mTOR modulation may help in developing safe and efficient nanotherapeutics to fight human disease. PMID- 26900006 TI - Synthetic Biology R&D Risks: Social-Institutional Contexts Matter! AB - Factors that shape actual research practices - 'social and institutional context' - typically are missing from considerations of synthetic biology R&D-related risk and containment. We argue that analyzing context is essential in identifying circumstances that create, amplify, or diminish risk, and in revealing new opportunities for avoiding or managing those risks. PMID- 26900007 TI - Halogen bonding. The role of the polarizability of the electron-pair donor. AB - The nature of F-BrX-R interactions (with X = F, Cl, Br, I and R = -H, -F) has been investigated through theoretical calculation of molecular potential electrostatic (MEP), molecular polarizability, atoms in molecules (AIM) analysis and energetic decomposition analysis (EDA). A detailed analysis of the MEPs reveals that considering only the static electrostatic interactions is not sufficient to explain the nature of these interactions. The molecular polarizabilities of X-R molecules suggest that the deformation capacity of the electronic cloud of the lone pairs of the X atom plays an important role in the stability of these complexes. The topological analysis of the L(r) = 1/4?(2)rho(r) function and the detailed analysis of the atomic quadrupole moments reveal that the BrX interactions are electrostatic in nature. The electron acceptor Br atom causes a polarization of the electronic cloud (electronic induction) on the valence shell of the X atom. Finally, the electrostatic forces and charge transfer play an important role not only in the stabilization of the complex, but also in the determination of the molecular geometry of equilibrium. The dispersive and polarization forces do not influence the equilibrium molecular geometry. PMID- 26900009 TI - Assessing aortic regurgitation severity from 2D, M-mode and pulsed wave Doppler echocardiographic measurements in horses. AB - Aortic regurgitation (AR) in horses can lead to left ventricular (LV) eccentric hypertrophy, ventricular arrhythmia and heart failure. Objective quantification of the severity of regurgitation is difficult. The aim of this study was to evaluate dimensional measurements, systolic time intervals and blood flow velocities, acquired by standard 2D, M-mode and pulsed wave Doppler echocardiography, for quantification of AR. Echocardiography was performed in 32 healthy horses and 35 horses with AR that were subdivided in three groups (mild, moderate or severe AR). From the recorded images LV, left atrial and aortic dimensions, systolic time intervals and aortic blood flow velocities were measured. Diastolic run-off in the aorta (AoDiastDecr) was calculated as the difference in aortic diameter between early diastole and late diastole. Stroke volume (SV) was calculated from pulsed wave Doppler measurements, by the bullet method (SVbullet) and by the area-length method. Pre-ejection period (PEP) and ejection time (LVET) were determined from the M-mode images. Horses with AR showed enlargement of the LV, left atrium and aorta compared to the control group. The SV, the AoDiastDecr and the rate of AoDiastDecr were significantly larger than controls. PEP decreased significantly in horses with AR, whereas LVET did not change. PEP and the newly defined variable AoDiastDecr proved to be easy to measure parameters that provided a good indication of AR severity. There was increased SV in horses with AR using all three methods, but SVbullet was superior for the detection of increased AR severity. PMID- 26900008 TI - A simplified method of walking track analysis to assess short-term locomotor recovery after acute spinal cord injury caused by thoracolumbar intervertebral disc extrusion in dogs. AB - The purpose of this study was to evaluate a simplified method of walking track analysis to assess treatment outcome in canine spinal cord injury. Measurements of stride length (SL) and base of support (BS) were made using a 'finger painting' technique for footprint analysis in all limbs of 20 normal dogs and 27 dogs with 28 episodes of acute thoracolumbar spinal cord injury (SCI) caused by spontaneous intervertebral disc extrusion. Measurements were determined at three separate time points in normal dogs and on days 3, 10 and 30 following decompressive surgery in dogs with SCI. Values for SL, BS and coefficient of variance (COV) for each parameter were compared between groups at each time point. Mean SL was significantly shorter in all four limbs of SCI-affected dogs at days 3, 10, and 30 compared to normal dogs. SL gradually increased toward normal in the 30 days following surgery. As measured by this technique, the COV SL was significantly higher in SCI-affected dogs than normal dogs in both thoracic limbs (TL) and pelvic limbs (PL) only at day 3 after surgery. BS-TL was significantly wider in SCI-affected dogs at days 3, 10 and 30 following surgery compared to normal dogs. These findings support the use of footprint parameters to compare locomotor differences between normal and SCI-affected dogs, and to assess recovery from SCI. Additionally, our results underscore important changes in TL locomotion in thoracolumbar SCI-affected dogs. PMID- 26900010 TI - Serum amyloid A1 secreted from UV-irradiated keratinocytes induces matrix metalloproteinase-1 in fibroblasts through toll-like receptor 4. AB - Ultraviolet (UV) irradiation on skin triggers photoageing-related phenotypes such as formation of wrinkles. UV ray upregulates matrix metalloproteinase-1 (MMP-1), which in turn degrades extracellular matrix proteins, mostly collagens. Serum amyloid A1 (SAA1) is an acute-phase protein of which plasma concentration increases in response to inflammation. Although the expression of SAA1 in the skin was reported, its function in the skin is yet to be studied. In this research, we found that the expression of SAA1 was increased in acute UV irradiated buttock skin and photoaged forearm skin in vivo. UV irradiation also increased SAA1 in normal human epidermal keratinocytes (NHEK), and treatment of recombinant human SAA1 (rhSAA1) induced MMP-1 in normal human dermal fibroblasts (NHDF) but not in NHEK. Next, we demonstrated that NHDF treated with UV irradiated keratinocyte-conditioned media showed the increased MMP-1 expression; however, this increase of MMP-1 in NHDF was inhibited by knockdown of SAA1 in NHEK. In addition, knockdown of Toll-like receptor 4 (TLR4) inhibited rhSAA1 induced MMP-1 expression in NHDF. Taken together, our data showed that UV-induced SAA1 production in NHEK, and this secreted SAA1 induced MMP-1 expression in NHDF in a paracrine manner through TLR4 signalling pathway. Therefore, our results suggest that SAA1 can be a potential mediator for UV-induced MMP-1 expression in human skin. PMID- 26900011 TI - Comparison of automatic summarisation methods for clinical free text notes. AB - OBJECTIVE: A major source of information available in electronic health record (EHR) systems are the clinical free text notes documenting patient care. Managing this information is time-consuming for clinicians. Automatic text summarisation could assist clinicians in obtaining an overview of the free text information in ongoing care episodes, as well as in writing final discharge summaries. We present a study of automated text summarisation of clinical notes. It looks to identify which methods are best suited for this task and whether it is possible to automatically evaluate the quality differences of summaries produced by different methods in an efficient and reliable way. METHODS AND MATERIALS: The study is based on material consisting of 66,884 care episodes from EHRs of heart patients admitted to a university hospital in Finland between 2005 and 2009. We present novel extractive text summarisation methods for summarising the free text content of care episodes. Most of these methods rely on word space models constructed using distributional semantic modelling. The summarisation effectiveness is evaluated using an experimental automatic evaluation approach incorporating well-known ROUGE measures. We also developed a manual evaluation scheme to perform a meta-evaluation on the ROUGE measures to see if they reflect the opinions of health care professionals. RESULTS: The agreement between the human evaluators is good (ICC=0.74, p<0.001), demonstrating the stability of the proposed manual evaluation method. Furthermore, the correlation between the manual and automated evaluations are high (> 0.90 Spearman's rho). Three of the presented summarisation methods ('Composite', 'Case-Based' and 'Translate') significantly outperform the other methods for all ROUGE measures (p<0.05, Wilcoxon signed-rank test and Bonferroni correction). CONCLUSION: The results indicate the feasibility of the automated summarisation of care episodes. Moreover, the high correlation between manual and automated evaluations suggests that the less labour-intensive automated evaluations can be used as a proxy for human evaluations when developing summarisation methods. This is of significant practical value for summarisation method development, because manual evaluation cannot be afforded for every variation of the summarisation methods. Instead, one can resort to automatic evaluation during the method development process. PMID- 26900012 TI - 3D flexible water channel: stretchability of nanoscale water bridge. AB - Artificial water channels can contribute to a better understanding of natural water channels and offer a highly selective, advanced conductance system. Most studies use nanotubes, however it is difficult to fabricate a flexible structure, and the nanosized diameter brings nanoconfinement effects, and nanotube toxicity arouses biosafety concerns. In this paper, we use an electric field to restrain the water molecules to form a nanoscale water bridge as an artificial water channel to connect a separated solid plate by molecular dynamics simulations. We observe strong 3D flexible stretchability in the water bridge, maintaining a variable length and an arbitrary angle for a considerably long time. The stretching of the water bridge enables it to be polarized at an arbitrary angle and the stretchability is linearly dependent upon the polarization strength. More interestingly, we show the possibility of establishing complex water networks, e.g., triangle, rectangle, hexagon, and tetrahedron-tetrahedron water networks. Our results may help realize structurally flexible and environmentally friendly water channels for lab-on-a-chip applications in nanofluidics. PMID- 26900013 TI - Protective upregulation of activating transcription factor-3 against glutamate neurotoxicity in neuronal cells under ischemia. AB - This study evaluates the pathological role of the stress sensor activating transcription factor-3 (ATF3) in ischemic neurotoxicity. Upregulation of the transcript and protein for ATF3 was seen 2-10 hr after reperfusion in the ipsilateral cerebral hemisphere of mice with transient middle cerebral artery occlusion for 2 hr. Immunohistochemical analysis confirmed the expression of ATF3 by cells immunoreactive for a neuronal marker in neocortex, hippocampus, and striatum within 2 hr after reperfusion. In murine neocortical neurons previously cultured under ischemic conditions for 2 hr, transient upregulation of both Atf3 and ATF3 expression was similarly found during subsequent culture for 2-24 hr under normoxia. Lentiviral overexpression of ATF3 ameliorated the neurotoxicity of glutamate (Glu) in cultured murine neurons along with a slight but statistically significant inhibition of both Fluo-3 and rhodamine-2 fluorescence increases by N-methyl-D-aspartate. Similarly, transient upregulation was seen in Atf3 and ATF3 expression during the culture for 48 hr in neuronal Neuro2A cells previously cultured under ischemic conditions for 2 hr. Luciferase reporter analysis with ATF3 promoter together with immunoblotting revealed the possible involvement of several transcription factors responsive to extracellular and intracellular stressors in the transactivation of the Atf3 gene in Neuro2A cells. ATF3 could be upregulated to play a role in mechanisms underlying mitigation of the neurotoxicity mediated by the endogenous neurotoxin Glu at an early stage after ischemic signal inputs. PMID- 26900014 TI - Point-of-Care Testing in Bathhouses: A Narrative Inquiry into the Experience of Receiving a Positive Preliminary HIV Test Result. AB - With a call to increase the accessibility of HIV testing, point-of-care testing for HIV is being readily adopted, but little attention has been paid to the experiences of people being tested at HIV point-of-care sites. Some testing environments, such as bathhouses, promote testing for HIV in higher-risk groups. In this narrative inquiry study we explored the experiences of people testing positive for HIV through point-of-care while at a bathhouse. Three narrative threads for reconsidering the practice were identified: (a) seeing complexities, understanding testing decisions in relation to time, place, and social context; (b) recognizing the impact and significance of secret and silent stories; and (c) tentative and tension-filled connections to care. It is important to understand testing experiences across time, place, and in diverse social contexts. These experiences are embedded within the larger life histories of people and raise questions about adequate support, follow-up, and counseling. PMID- 26900015 TI - Using the Conceptual Model of Nursing and Health Policy to Examine Substance Abuse Treatment for Incarcerated Individuals. PMID- 26900016 TI - Tailoring electromagnetically induced transparency with different coupling mechanisms. AB - Tailoring electromagnetically induced transparency with two different coupling mechanisms has been numerically demonstrated. The results show that EIT based on simultaneous electric resonance and magnetic resonance has relatively larger coupling distance compared with that based on electric resonance near field coupling to magnetic resonance. The relatively large coupling distance is due to the relatively small susceptibility change. For EIT based on simultaneous electric resonance and magnetic resonance, not only incident electric field but also the incident magnetic field pays a role on the susceptibility of system. The influence of the incident magnetic field leads to relatively smaller susceptibility change compared with that based on electric resonance near field coupling to magnetic resonance. PMID- 26900017 TI - Quasi-static and dynamic properties of the intervertebral disc: experimental study and model parameter determination for the porcine lumbar motion segment. AB - PURPOSE: The study of axial loading is essential to determine the properties of intervertebral disc. The objectives of this work are (1) to quantify the mechanical properties of porcine lumbar intervertebral discs under static and cyclic compressive loading, and (2) to determine the parameters of a five parameter rheological model for porcine and compare them with those obtained for human lumbar intervertebral discs. METHODS: Thus, the porcine lumbar motion segments were subjected to quasi-static and dynamic compression tests. The quasi static tests were used to obtain the static stiffness coefficient at different strain rates, while the data from the cyclic compressive tests were used to both determine the dynamic stiffness coefficient and to be fitted in a 5-parameter model, in order to simulate the creep response of the porcine intervertebral discs. RESULTS: The results demonstrated that dynamic stiffness coefficient of porcine discs is between four and ten times higher than the static stiffness coefficient, depending on load applied. The parameters of the rheological model suggested a low permeability of nucleus and endplate during the fast response of porcine discs. In addition, the fast response in terms of displacement is four times higher than those documented for human discs. CONCLUSIONS: This study revealed that care must be taken on the comparison between porcine and human discs, since they present different behaviour under quasi-static and dynamic compressive loading. PMID- 26900018 TI - Unlocking the therapeutic potential of plant extracts. PMID- 26900019 TI - Evaporation-Induced Self-Assembly of Ultrathin Tungsten Oxide Nanowires over a Large Scale for Ultraviolet Photodetector. AB - Self-assembly of inorganic nanowires on a large scale directly on a substrate represents a great challenge. Starting from colloidally stable dispersions of ultrathin tungsten oxide nanowires, we successfully assemble the nanowires on a centimeter scale on flat or patterned substrates by a simple evaporation-induced self-assembly method. The capillary flow generated during the evaporation is responsible for the assembly of the nanowires. The concentration of the nanowire dispersion has a significant influence on the self-assembly behavior. Well aligned tungsten oxide nanowire thin films are achieved when the concentration of the dispersion is in the range from 0.5 to 3.0 mg/mL. While at higher concentrations disordered nanowire thin films with cracks are formed, lower concentrations do not result in the formation of a continuous thin film. A macroscopic device based on the self-assembled tungsten oxide nanowires is fabricated, exhibiting good performance for UV light detection. Our results may pave the road for integrating aligned ultrathin semiconductor nanowires into macroscopic devices for optoelectronic applications. PMID- 26900020 TI - Nuclear F-actin enhances the transcriptional activity of beta-catenin by increasing its nuclear localization and binding to chromatin. AB - Actin plays multiple roles both in the cytoplasm and in the nucleus. Cytoplasmic actin, in addition to its structural role in the cytoskeleton, also contributes to the subcellular localization of transcription factors by interacting with them or their partners. The transcriptional cofactor beta-catenin, which acts as an intracellular transducer of canonical Wnt signaling, indirectly associates with the cytoplasmic filamentous actin (F-actin). Recently, it has been observed that F-actin is transiently formed within the nucleus in response to serum stimulation and integrin signaling, and also during gene reprogramming. Despite these earlier observations, information about the function of nuclear F-actin is poorly defined. Here, by facilitating the accumulation of nuclear actin artificially, we demonstrate that polymerizing nuclear actin enhanced the nuclear accumulation and transcriptional function of beta-catenin. Our results also show that the nuclear F-actin colocalizes with beta-catenin and enhances the binding of beta-catenin to the downstream target genes of the Wnt/beta-catenin signaling pathway, including the genes for the cell cycle regulators c-myc and cyclin D, and the OCT4 gene. Nuclear F-actin itself also associated with these genes. Since Wnt/beta-catenin signaling has important roles in cell differentiation and pluripotency, our observations suggest that nuclear F-actin formed during these biological processes is involved in regulating Wnt/beta-catenin signaling. PMID- 26900022 TI - Introduction to the 1st International Symposium on Phytochemicals in Medicine and Food (ISPMF 2015). AB - The 1st International Symposium on Phytochemicals in Medicine and Food (ISPMF 2015) was held in Shanghai, China, from June 26th to 29th, 2015. The 1st ISPMF was organized by the Phytochemical Society of Europe (PSE) and the Phytochemical Society of Asia (PSA). More than 270 scientists from 48 countries attended this meeting. The program of ISPMF 2015 consisted of 12 plenary lectures, 20 invited talks, and 55 short oral presentations in 16 sessions, including phytochemistry, phytomedicine, pharmacology, and application of phytochemicals in medicine and food. The 1st ISPMF has obtained support from Critical Reviews in Food Science and Nutrition, Food Chemistry, Phytochemistry Reviews, and Nutrients. As supported by Prof. Thomas F. Hofmann, a special issue on Journal of Agricultural and Food Chemistry (ACS) for the 1st ISPMF was initiated in January 2015. PMID- 26900021 TI - Copper stress-induced changes in leaf soluble proteome of Cu-sensitive and tolerant Agrostis capillaris L. populations. AB - Changes in leaf soluble proteome were explored in 3-month-old plants of metallicolous (M) and nonmetallicolous (NM) Agrostis capillaris L. populations exposed to increasing Cu concentrations (1-50 MUM) to investigate molecular mechanisms underlying plant responses to Cu excess and tolerance of M plants. Plants were cultivated on perlite (CuSO4 spiked-nutrient solution). Soluble proteins, extracted by the trichloroacetic acid/acetone procedure, were separated with 2-DE (linear 4-7 pH gradient). Analysis of CCB-stained gels (PDQuest) reproducibly detected 214 spots, and 64 proteins differentially expressed were identified using LC-MS/MS. In both populations, Cu excess impacted both light dependent (OEE, cytochrome b6-f complex, and chlorophyll a-b binding protein), and -independent (RuBisCO) photosynthesis reactions, more intensively in NM leaves (ferredoxin-NADP reductase and metalloprotease FTSH2). In both populations, upregulation of isocitrate dehydrogenase and cysteine/methionine synthases respectively suggested increased isocitrate oxidation and enhanced need for S-containing amino-acids, likely for chelation and detoxification. In NM leaves, an increasing need for energetic compounds was indicated by the stimulation of ATPases, glycolysis, pentose phosphate pathway, and Calvin cycle enzymes; impacts on protein metabolism and oxidative stress increase were respectively suggested by the rise of chaperones and redox enzymes. Overexpression of a HSP70 may be pivotal for M Cu tolerance by protecting protein metabolism. All MS data have been deposited in the ProteomeXchange with the dataset identifier PXD001930 (http//proteomecentral.proteomexchange.org/dataset/PXD001930). PMID- 26900023 TI - Epigenetics: A three-state model for epigenetic silencing. PMID- 26900024 TI - Complex traits: Integrating gene variation and expression to understand complex traits. PMID- 26900025 TI - Feeling Closer to the Future Self and Doing Better: Temporal Psychological Mechanisms Underlying Academic Performance. AB - This research examined the function of future self-continuity and its potential downstream consequences for academic performance through relations with other temporal psychological factors and self-control. We also addressed the influence of cultural factors by testing whether these relations differed by college generation status. Undergraduate students enrolled at a large public university participated in two studies (Study 1: N = 119, Mage = 20.55, 56.4% women; Study 2: N = 403, Mage = 19.83, 58.3% women) in which they completed measures of temporal psychological factors and psychological resources. In Study 2, we also obtained academic records to link responses to academic performance. Future self continuity predicted subsequent academic performance and was related positively to future focus, negatively to present focus, and positively to self-control. Additionally, the relation between future focus and self-control was stronger for continuing-generation college students than first-generation college students. Future self-continuity plays a pivotal role in academic contexts. Findings suggest that it may have positive downstream consequences on academic achievement by directing attention away from the present and toward the future, which promotes self-control. Further, the strategy of focusing on the future may be effective in promoting self-control only for certain cultural groups. PMID- 26900026 TI - Airborne transmission from a neonate with Netherton syndrome during an outbreak of MRSA. AB - We encountered a 4 month outbreak of methicillin-resistant Staphylococcus aureus (MRSA) colonization or infection that was difficult to control despite implementation of standard prevention methods. A neonate with Netherton syndrome had accelerated scaling of the skin and continued positive results for MRSA from clinical samples. The results of air sampling suggested the possibility of airborne transmission. The MRSA outbreak stopped after the patient was transferred to an isolation room, suggesting that airborne MRSA can play a role in MRSA colonization. Isolation rooms should be considered in specific circumstances, as described in the present study. PMID- 26900027 TI - Corrigendum: Site Specific Genetic Incorporation of Azidophenylalanine in Schizosaccharomyces pombe. PMID- 26900028 TI - Heterotrophic respiration does not acclimate to continuous warming in a subtropical forest. AB - As heterotrophic respiration (R(H)) has great potential to increase atmospheric CO2 concentrations, it is important to understand warming effects on R(H) for a better prediction of carbon-climate feedbacks. However, it remains unclear how R(H) responds to warming in subtropical forests. Here, we carried out trenching alone and trenching with warming treatments to test the climate warming effect on R(H) in a subtropical forest in southwestern China. During the measurement period, warming increased annual soil temperature by 2.1 degrees C, and increased annual mean R(H) by 22.9%. Warming effect on soil temperature (WE(T)) showed very similar pattern with warming effect on R(H) (WE(RH)), decreasing yearly. Regression analyses suggest that WE(RH) was controlled by WE(T) and also regulated by the soil water content. These results showed that the decrease of WE(RH) was not caused by acclimation to the warmer temperature, but was instead due to decrease of WE(T). We therefore suggest that global warming will accelerate soil carbon efflux to the atmosphere, regulated by the change in soil water content in subtropical forests. PMID- 26900029 TI - Transition-metal free thiocyanooxygenation of functionalized alkenes: facile routes to SCN-containing dihydrofurans and lactones. AB - An efficient transition-metal free tandem cyclization of functionalized alkenes with easily available thiocyanate salts has been developed under mild conditions. This protocol offers a simple, easy-to-handle, and atom-economical method for the synthesis of SCN-containing dihydrofurans and lactones with good to excellent yields. A detailed mechanistic investigation indicates that a tandem radical pathway is involved in this transformation. PMID- 26900030 TI - Correlating thyroid cytology and histopathology: Implications for molecular testing. AB - BACKGROUND: A gene expression classifier (GEC) has been advocated in management of some indeterminate nodules without surgery. We assessed the potential negative predictive value (NPV) of the GEC at our academic center. METHODS: Retrospectively, all cytologically indeterminate fine-needle aspirates (FNAs) diagnosed by University of Iowa cytopathologists over a 3-year period were identified. Histopathologic findings were recorded. Using published sensitivity and specificity, NPVs were calculated. RESULTS: Of 178 nodules (17, 135, and 26 in classes III, IV, and V, respectively), 71 (40%) were malignant. Prevalence of malignancy was 41%, 29%, and 96% for classes III, IV, and V, respectively. Using sensitivities and specificities for the GEC, NPVs were 91% for the cohort: 88%, 92%, and 26% for classes III, IV, and V, respectively. CONCLUSION: Molecular testing should be associated with an NPV no lower than that from clinical criteria alone. With the prevalences reported, GEC use may result in more missed cancer diagnoses. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: 1104-1106, 2016. PMID- 26900032 TI - Oral PrEP for young African women and men. PMID- 26900033 TI - Differences between clinical "snap-shot" and "real-life" assessments of lumbar spine alignment and motion - What is the "real" lumbar lordosis of a human being? AB - The individual lumbar lordosis and lumbar motion have been identified to play an important role in pathogenesis of low back pain and are essential references for preoperative planning and postoperative evaluation. The clinical "gold-standard" for measuring lumbar lordosis and its motion are radiological "snap-shots" taken while standing and during upper-body flexion and extension. The extent to which these clinically assessed values characterise lumbar alignment and its motion in daily life merits discussion. A non-invasive measurement-system was employed to measure lumbar lordosis and lumbar motion in 208 volunteers (age: 20-74yrs; ?/?: 115/93). For an initial short-term measurement, comparable with the clinical "snap-shot", lumbar lordosis and its motion were assessed while standing and during flexion and extension. Subsequently, volunteers were released to their daily lives while wearing the device, and measurements were performed during the following 24h. The average lumbar lordosis during 24h (8.0 degrees ) differed significantly from the standardised measurement while standing (33.3 degrees ). Ranges of motion were significantly different throughout the day compared to standing measurements. The influence of the factors age and gender on lordosis and its motion resulted in conflicting results between long- and short-term measurements. In conclusion, results of short-term examinations differ considerably from the average values during real-life. These findings might be important for surgical planning and increase the awareness of the biomechanical challenges that spinal structures and implants face in real-life. Furthermore, long-term assessments of spinal alignment and motion during daily life can provide valid data on spinal function and can reveal the importance of influential factors. PMID- 26900034 TI - Hemodynamics of left internal mammary artery bypass graft: Effect of anastomotic geometry, coronary artery stenosis, and postoperative time. AB - Although the left internal mammary artery (LIMA) bypass graft is the best choice for surgical revascularization, its hemodynamics are still complex and can result in long-term graft failure. Here, we performed a hemodynamic analysis of the LIMA coronary artery with end-to-side/side-to-side anastomoses based on 15 patient specific CTA images at various postoperative periods. We hypothesize that hemodynamic patterns are determined by the interplay of LIMA geometry, anastomotic configuration, and severity of native coronary artery stenosis, which are strongly affected by the postoperative time. A 3D finite volume method with the inlet pressure wave and outlet resistance boundary conditions was used to compute the distribution of pressure and flow, from which the time-averaged wall shear stress (TAWSS), oscillation shear index (OSI), time-averaged WSS gradient (TAWSSG), and transverse WSS (transWSS) were determined. To characterize the hemodynamic environment, we defined surface area ratios of low TAWSS (<=4dynes/cm(2)), high OSI (>=0.15), TAWSSG (>=500dynes/cm(3)), and transWSS (>=6dynes/cm(2)) in the LIMA graft and at the anastomosis between LIMA graft and coronary artery. These ratios were determined by the interplay of multiple morphometric parameters in the LIMA-coronary artery, but increased with postoperative time. These findings have significant implications for understanding LIMA graft patency. PMID- 26900031 TI - Barriers to a cure for HIV in women. AB - INTRODUCTION: Distinct biological factors exist that affect the natural history of HIV and the host immune response between women and men. These differences must be addressed to permit the optimal design of effective HIV eradication strategies for much of the HIV-positive population. METHODS AND RESULTS: Here, we review the literature on sex-based differences in HIV pathogenesis and natural history in tissues and anatomic compartments, HIV latency and transcriptional activity, and host immunity including the role of sex hormones. We then outline the potential effects of these differences on HIV persistence, and on the safety and efficacy of HIV eradication and curative interventions. Finally, we discuss the next steps necessary to elucidate these factors to achieve a cure for HIV, taking in account the complex ethical issues and the regulatory landscape in the hopes of stimulating further research and awareness in these areas. CONCLUSIONS: Targeted enrollment of women in clinical trials and careful sex-based analysis will be crucial to gain further insights into sex-based differences in HIV persistence and to design sex-specific approaches to HIV eradication, if required. PMID- 26900035 TI - A database of lumbar spinal mechanical behavior for validation of spinal analytical models. AB - Data from two experimental studies with eight specimens each of spinal motion segments and/or intervertebral discs are presented in a form that can be used for comparison with finite element model predictions. The data include the effect of compressive preload (0, 250 and 500N) with quasistatic cyclic loading (0.0115Hz) and the effect of loading frequency (1, 0.1, 0.01 and 0.001Hz) with a physiological compressive preload (mean 642N). Specimens were tested with displacements in each of six degrees of freedom (three translations and three rotations) about defined anatomical axes. The three forces and three moments in the corresponding axis system were recorded during each test. Linearized stiffness matrices were calculated that could be used in multi-segmental biomechanical models of the spine and these matrices were analyzed to determine whether off-diagonal terms and symmetry assumptions should be included. These databases of lumbar spinal mechanical behavior under physiological conditions quantify behaviors that should be present in finite element model simulations. The addition of more specimens to identify sources of variability associated with physical dimensions, degeneration, and other variables would be beneficial. Supplementary data provide the recorded data and Matlab(r) codes for reading files. Linearized stiffness matrices derived from the tests at different preloads revealed few significant unexpected off-diagonal terms and little evidence of significant matrix asymmetry. PMID- 26900036 TI - Insights into the co-localization of magnitude-based versus direction-based indicators of disturbed shear at the carotid bifurcation. AB - The observed co-localization of disturbed flow and lesion prevalence at predisposed districts such as the carotid bifurcation has led to the identification of the wall shear stress (WSS) as biomechanical localizing factor of vascular dysfunction. In particular, a proatherogenic role is attributed to low and oscillatory WSS. However, the endothelial cells (ECs) are exposed to a complex hemodynamic milieu that can be only partially described by low/oscillatory WSS. Recently, in the attempt to close this gap, descriptors of the complex multidirectional nature of WSS have been proposed, i.e., the axial component of WSS (aligned with the vessel's centerline, to quantify flow reversal), and the transverse WSS (transWSS, quantifying the WSS component orthogonal to the cycle averaged WSS direction). Here we explore the relationship between recently-proposed indicators quantifying WSS multidirectionality and "established" WSS-based hemodynamic descriptors of low/oscillatory WSS, in a representative sample (N=46) of subject-specific computational hemodynamics models of ostensibly normal carotid bifurcations. To do it, we quantitatively assess the co-localization of those descriptors at the luminal surface, aiming at providing connections among the peculiar hemodynamic features captured by the different descriptors. According to our findings: (1) regions of flow reversal are moderately co-localized with low WSS; (2) high WSS oscillations (quantified by the oscillatory shear index, OSI) at the carotid bulb are prevalently aligned with the main flow, where flow reversal is predominant; (3) regions where transWSS is high do not co-localize with the other descriptors. We suggest that the investigated WSS-based descriptors might represent different hemodynamic disturbances with different impact on ECs homeostasis, potentially being part of WSS phenotypes more effective in localizing the map of vascular atherosclerotic lesions. PMID- 26900037 TI - Finite element simulation of articular contact mechanics with quadratic tetrahedral elements. AB - Although it is easier to generate finite element discretizations with tetrahedral elements, trilinear hexahedral (HEX8) elements are more often used in simulations of articular contact mechanics. This is due to numerical shortcomings of linear tetrahedral (TET4) elements, limited availability of quadratic tetrahedron elements in combination with effective contact algorithms, and the perceived increased computational expense of quadratic finite elements. In this study we implemented both ten-node (TET10) and fifteen-node (TET15) quadratic tetrahedral elements in FEBio (www.febio.org) and compared their accuracy, robustness in terms of convergence behavior and computational cost for simulations relevant to articular contact mechanics. Suitable volume integration and surface integration rules were determined by comparing the results of several benchmark contact problems. The results demonstrated that the surface integration rule used to evaluate the contact integrals for quadratic elements affected both convergence behavior and accuracy of predicted stresses. The computational expense and robustness of both quadratic tetrahedral formulations compared favorably to the HEX8 models. Of note, the TET15 element demonstrated superior convergence behavior and lower computational cost than both the TET10 and HEX8 elements for meshes with similar numbers of degrees of freedom in the contact problems that we examined. Finally, the excellent accuracy and relative efficiency of these quadratic tetrahedral elements was illustrated by comparing their predictions with those for a HEX8 mesh for simulation of articular contact in a fully validated model of the hip. These results demonstrate that TET10 and TET15 elements provide viable alternatives to HEX8 elements for simulation of articular contact mechanics. PMID- 26900038 TI - Computer simulations of thermal tissue remodeling during transvaginal and transurethral laser treatment of female stress urinary incontinence. AB - BACKGROUND AND OBJECTIVES: A non-surgical method is being developed for treating female stress urinary incontinence by laser thermal remodeling of subsurface tissues with applied surface tissue cooling. Computer simulations of light transport, heat transfer, and thermal damage in tissue were performed, comparing transvaginal and transurethral approaches. STUDY DESIGN/MATERIALS AND METHODS: Monte Carlo (MC) simulations provided spatial distributions of absorbed photons in the tissue layers (vaginal wall, endopelvic fascia, and urethral wall). Optical properties (n,MUa ,MUs ,g) were assigned to each tissue at lambda = 1064 nm. A 5-mm-diameter laser beam and incident power of 5 W for 15 seconds was used, based on previous experiments. MC output was converted into absorbed energy, serving as input for finite element heat transfer simulations of tissue temperatures over time. Convective heat transfer was simulated with contact probe cooling temperature set at 0 degrees C. Variables used for thermal simulations (kappa,c,rho) were assigned to each tissue layer. MATLAB code was used for Arrhenius integral thermal damage calculations. A temperature matrix was constructed from ANSYS output, and finite sum was incorporated to approximate Arrhenius integral calculations. Tissue damage properties (Ea ,A) were used to compute Arrhenius sums. RESULTS: For the transvaginal approach, 37% of energy was absorbed in the endopelvic fascia target layer with 0.8% deposited beyond it. Peak temperature was 71 degrees C, the treatment zone was 0.8-mm-diameter, and 2.4 mm of the 2.7-mm-thick vaginal wall was preserved. For transurethral approach, 18% energy was absorbed in endopelvic fascia with 0.3% deposited beyond the layer. Peak temperature was 80 degrees C, treatment zone was 2.0-mm-diameter, and 0.6 mm of 2.4-mm-thick urethral wall was preserved. CONCLUSIONS: Computer simulations suggest that transvaginal approach is more feasible than transurethral approach. Lasers Surg. Med. 49:198-205, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 26900039 TI - CARD9 knockout ameliorates myocardial dysfunction associated with high fat diet induced obesity. AB - Obesity is associated with chronic inflammation which plays a critical role in the development of cardiovascular dysfunction. Because the adaptor protein caspase recruitment domain-containing protein 9 (CARD9) in macrophages regulates innate immune responses via activation of pro-inflammatory cytokines, we hypothesize that CARD9 mediates the pro-inflammatory signaling associated with obesity en route to myocardial dysfunction. C57BL/6 wild-type (WT) and CARD9(-/-) mice were fed normal diet (ND, 12% fat) or a high fat diet (HFD, 45% fat) for 5months. At the end of 5-month HFD feeding, cardiac function was evaluated using echocardiography. Cardiomyocytes were isolated and contractile properties were measured. Immunofluorescence was performed to detect macrophage infiltration in the heart. Heart tissue homogenates, plasma, and supernatants from isolated macrophages were collected to measure the concentrations of pro-inflammatory cytokines using ELISA kits. Western immunoblotting analyses were performed on heart tissue homogenates and isolated macrophages to explore the underlying signaling mechanism(s). CARD9 knockout alleviated HFD-induced insulin resistance and glucose intolerance, prevented myocardial dysfunction with preserved cardiac fractional shortening and cardiomyocyte contractile properties. CARD9 knockout also significantly decreased the number of infiltrated macrophages in the heart with reduced myocardium-, plasma-, and macrophage-derived cytokines including IL 6, IL-1beta and TNFalpha. Finally, CARD9 knockout abrogated the increase of p38 MAPK phosphorylation, the decrease of LC3BII/LC3BI ratio and the up-regulation of p62 expression in the heart induced by HFD feeding and restored cardiac autophagy signaling. In conclusion, CARD9 knockout ameliorates myocardial dysfunction associated with HFD-induced obesity, potentially through reduction of macrophage infiltration, suppression of p38 MAPK phosphorylation, and preservation of autophagy in the heart. PMID- 26900040 TI - Child and environmental risk factors predicting readiness for learning in children at high risk of dyslexia. AB - We investigate the role of distal, proximal, and child risk factors as predictors of reading readiness and attention and behavior in children at risk of dyslexia. The parents of a longitudinal sample of 251 preschool children, including children at family risk of dyslexia and children with preschool language difficulties, provided measures of socioeconomic status, home literacy environment, family stresses, and child health via interviews and questionnaires. Assessments of children's reading-related skills, behavior, and attention were used to define their readiness for learning at school entry. Children at family risk of dyslexia and children with preschool language difficulties experienced more environmental adversities and health risks than controls. The risks associated with family risk of dyslexia and with language status were additive. Both home literacy environment and child health predicted reading readiness while home literacy environment and family stresses predicted attention and behavior. Family risk of dyslexia did not predict readiness to learn once other risks were controlled and so seems likely to be best conceptualized as representing gene environment correlations. Pooling across risks defined a cumulative risk index, which was a significant predictor of reading readiness and, together with nonverbal ability, accounted for 31% of the variance between children. PMID- 26900041 TI - Arteriovenous malformation of the iris. Two cases. AB - CASE REPORT: A 50-year-old patient was seen during a regular follow up. The main complaint was decreased near-sight vision. Biomicroscopy showed a vascular malformation on the temporal sector of the iris in the left eye, diagnosed as an arteriovenous malformation. A second case of similar features is also presented. DISCUSSION: The vascular malformations of the iris may be asymptomatic and go unnoticed or cause recurrent spontaneous hyphemas. Treatment must be individualised and may range from observation to photocoagulation with laser, or even surgery. PMID- 26900042 TI - Five-year experience of tele-ophthalmology for diabetic retinopathy screening in a rural population. AB - OBJECTIVE: To identify the prevalence and risk factors of diabetic retinopathy (DR) among rural inhabitants included in a tele-ophthalmology program. To analyse diagnostic accuracy among primary care physicians, concordance with ophthalmologists, and financial savings. MATERIAL AND METHODS: An observational randomised study was conducted on 394 patients included in a tele-ophthalmology program (from January 2010 to January 2015). An analysis was performed on the clinical characteristics, DR findings in retinography images, and correspondence between the request for a second interpretation by an ophthalmologist, and previously established criteria for it: presence of moderate to severe DR, vision loss, poor image quality and/or intraocular pressure >22mmHg. Statistical analysis was performed using the SPSS program (Student t and chi(2) tests). RESULTS: DR prevalence was 12.1%. Patients with glycosylated haemoglobin values >7.68% or those treated with a combination of insulin and oral antidiabetic drugs showed a higher risk of DR (P<.05). 43.3% of patients correctly referred to ophthalmologists showed moderate to severe DR. Unnecessary referrals to specialists were improved from 91.7% in 2010 to 98.6% in 2014. It is estimated that the program has made a total saving of ?152,550.45. CONCLUSIONS: Tele ophthalmology programs are a useful tool in DR screening. Primary care physicians are able to distinguish patients who need specialist care, avoiding unnecessary referrals to ophthalmologists, and saving costs. PMID- 26900043 TI - Cost of myopic patients with and without myopic choroidal neovascularisation. AB - OBJECTIVE: To study the costs associated with high myopia (HM) with choroidal neovascularisation (mCNV) or without mCNV. METHODS: Observational, retrospective, cross-sectional, and multicentre study (HM and mCNV) conducted on adult patients. Annualised medical direct cost (MDC) from the perspective of the National Health System, the non-medical direct cost (nMDC) from the patient perspective, and productivity losses were calculated. RESULTS: A total of 137 mCNV and 48 HM patients were included (mean age [SD]: 55.1 [2.8] vs. 54.7 [13.8]; P=.2), with 80% women in both groups. The observation time (months) ranged from 17.9 (9.6) right eye (RE) and 20.0 (9.7), left eye (LE) in mCNV and 47.1 (21.5) RE/45.5 (20.7) LE in MM. A higher percentage of emergency room visits was observed in mCNV vs. HM patients (41.7 vs. 25%; P=.06) and retinal specialists (91.2 vs. 77.1%; P=.01). The MDC was higher in mCNV: ? 1,985 (95% CI: 1772-2198) vs. ? 356 (251-480) HM, P<.001. The nMDC was also higher in mCNV: ? 256 (11-524) vs. ?19 (11-26) HM, P>.4. The number of affected eyes, the follow-up time, and the mCNV were factors associated with direct costs. The impact on work productivity was higher in mCNV (quite/very concerned): 27.7 vs. 10.4% HM. The mCNV showed a significant association with activity impairment (OR: 3.47, 95% CI: 10.101 1.195). CONCLUSIONS: mCNV involves higher medical costs than HM. In addition, mCNV patients have a greater need of care and assistive devices, and greater impact of the disease in their work productivity. PMID- 26900044 TI - Parinaud "plus" syndrome in a patient with dysgerminoma. AB - CLINICAL CASE: A 33-year-old male diagnosed with Parinaud's syndrome, exotropia and post-papillary oedema optic atrophy in his left eye. A pineal germinoma was diagnosed after performing neuroimaging scans and a stereotactic biopsy. He was treated with chemotherapy and radiotherapy, showing a complete pathological response. The Parinaud's syndrome persists one year after diagnosis and the patient has refused to have strabismus surgery. DISCUSSION: Parinaud's syndrome consists of a supranuclear vertical gaze palsy resulting from damage to the midbrain tectum. The involvement of adjacent structures leads to the "Parinaud plus" syndrome. When a Parinaud's syndrome is accompanied by diplopia ("Parinaud plus" syndrome), extension of the injury into adjacent areas must be considered. PMID- 26900046 TI - Editorial Comment. PMID- 26900045 TI - Repurposing Drugs to Target the Diabetes Epidemic. AB - Despite major investment by pharmaceutical companies in conventional drug discovery pipelines, development of new drugs has failed to keep up with the increasing incidence of many diseases, including type 2 diabetes (T2D). Drug repurposing, where existing drugs are applied to a new indication, is gaining momentum as a successful approach to overcome the bottlenecks commonly encountered with conventional approaches. Repurposing takes advantage of available information on the molecular pharmacology of clinical agents to drastically shorten drug development timelines. This review discusses recent advances in the discovery of new antidiabetic agents using repurposing strategies. PMID- 26900047 TI - Editorial Comment. PMID- 26900048 TI - New "all-in-one" device for mesh plug hernioplasty: the Trabucco repair. AB - Although Mesh Plug Repair (MPR) represents an effective method for the treatment of groin hernia, some criticisms still concern adverse effects related to the plug (shrinkage, chronic pain, migration and erosion). Different mesh and plug devices have been proposed in the past mostly to prevent migration but none of these achieved the same popularity as the cone or flower-shaped plug. Authors hereby present a pilot study with a new tridimensional device, denominated NeT Plug and Patch, that avoids any risk of migration. Results after 12 months follow up have demonstrated low incidence of postoperative and chronic pain, with both patients and surgeons greatly satisfied. NeT Plug and Patch has proven to achieve a simple and effective repair for primary inguinal hernias. KEY WORDS: Mesh-plug, Plug migration, Trabucco repair. PMID- 26900049 TI - The impact mitigation of a heterojunction nanotube-water system: behavior and mechanism. AB - A novel nanofluidic impact protection system is introduced in this paper, consisting of hydrophobic heterojunction carbon nanotubes (HCNTs) and water molecules. When the capillary resistance of the nanopores is overcome, water molecules can infiltrate into nanopores such as to convert external impact energy into excessive surface energy. A model of a single HCNT with water molecules in a reservoir is established and validated. The effects of several dominant parameters (e.g., nanopore size, impact velocity) are evaluated, and the potential mechanism is illustrated. The effect of the carbon nanotube structure on the nanofluidic behavior of the HCNT-water system is investigated. Results reveal that the segment of carbon nanotubes close to the water reservoir determines the energy absorption efficiency of the system. PMID- 26900050 TI - The use of experimental design in the optimization of risperidone biodegradable nanoparticles: in vitro and in vivo study. AB - The aim of this study was optimization of risperidone (model drug) biodegradable nanoparticles utilizing emulsion-solvent evaporation technique. Box-Behnken design was adopted to optimize the preparation process. Optimized nanoparticles were characterized for surface morphology using scanning electron microscope. Pharmacokinetic parameters were compared with the marketed tablets. Results revealed that the optimized formula showed 297.37 nm, 85.12%, and 59.79% for Y1, Y2, and Y3, respectively. Optimized formula showed significant improved bioavailability compared with marketed tablets. Successful achievement of prolonged risperidone release with improved bioavailability is expected to maximize patients' adherence to their antipsychotic drug therapy and to minimize risk of relapse during maintenance therapy. PMID- 26900051 TI - Effects of oral exposure to silver nanoparticles on the sperm of rats. AB - It has been demonstrated that exposure to silver nanoparticles (AgNPs) can induce toxicological effects in rodents. In this study, we investigated whether sub chronic oral exposure to different doses of polyvinil pyrrolidone (PVP)-coated AgNPs (PVP-AgNPs) (50, 100 and 200mg/kg/day) could induce harmful effects on epididymal sperm rat parameters. Sperm motility, viability and morphology were examined. Moreover, a histological evaluation of testis and epididymis was also performed. High doses of PVP-AgNPs showed higher sperm morphology abnormalities, while a progressive, but not significant effect, was observed in other sperm parameters. The current results suggest that oral sub-chronic exposure to PVP AgNPs induces slight toxicological effects in sperm rat parameters. PMID- 26900052 TI - Forensic study of Schistosoma japonicum eggs found in an autopsy case. PMID- 26900053 TI - Clinical and echocardiographic findings in an 8 year old Brown Swiss cow with myocardial abscess. AB - Intramyocardial abscesses are rare in cattle and may lead to unspecific clinical signs. This case report describes the clinical and echocardiographic findings in an 8 year old Brown Swiss cow presented with an intramural myocardial abscess. The main clinical findings were anorexia, drop in milk yield, fever, tachycardia, and hyperfibrinogenemia. Neither heart murmurs nor cardiac arrhythmias were present on auscultation. Transthoracic echocardiographic examination revealed a prominent intramural mass embedded in the left ventricular free wall and bulging into the lumen of the left ventricle. Diagnosis was confirmed at necropsy. A culture of the abscess grew Trueperella pyogenes. PMID- 26900054 TI - Rasmussen's legacy and the long arm of rational choice. AB - Rational choice theory says that operators and others make decisions by systematically and consciously weighing all possible outcomes along all relevant criteria. This paper first traces the long historical arm of rational choice thinking in the West to Judeo-Christian thinking, Calvin and Weber. It then presents a case study that illustrates the consequences of the ethic of rational choice and individual responsibility. It subsequently examines and contextualizes Rasmussen's legacy of pushing back against the long historical arm of rational choice, showing that bad outcomes are not the result of human immoral choice, but the product of normal interactions between people and systems. If we don't understand why people did what they did, Rasmussen suggested, it is not because people behaved inexplicably, but because we took the wrong perspective. PMID- 26900055 TI - What do prisoners eat? Nutrient intakes and food practices in a high-secure prison. AB - There are limited studies on the adequacy of prisoner diet and food practices, yet understanding these are important to inform food provision and assure duty of care for this group. The aim of this study was to assess the dietary intakes of prisoners to inform food and nutrition policy in this setting. This research used a cross-sectional design with convenience sampling in a 945-bed male high-secure prison. Multiple methods were used to assess food available at the group level, including verification of food portion, quality and practices. A pictorial tool supported the diet history method. Of 276 eligible prisoners, 120 dietary interviews were conducted and verified against prison records, with 106 deemed plausible. The results showed the planned food to be nutritionally adequate, with the exception of vitamin D for older males and long-chain fatty acids, with Na above upper limits. The Australian dietary targets for chronic disease risk were not achieved. High energy intakes were reported with median 13.8 (se 0.3) MJ. Probability estimates of inadequate intake varied with age groups: Mg 8 % (>30 years), 2.9 % (70 years), 1.5 % (<70 years); folate 3.5 %; Zn and I 2.7 %; and vitamin A 2.3 %. Nutrient intakes were greatly impacted by self-funded snacks. Results suggest the intakes to be nutritionally favourable when compared with males in the community. This study highlights the complexity of food provision in the prison environment and also poses questions for population-level dietary guidance in delivering appropriate nutrients within energy limits. PMID- 26900057 TI - Discovery of HLA-A*11:01:69, a novel HLA-A*11:01 variant, in a Taiwanese hematopoietic stem cell donor. AB - One nucleotide replacement at residue 210 of HLA-A*11:01:01:01 results in a novel allele, HLA-A*11:01:69. PMID- 26900056 TI - Editorial Comment. PMID- 26900058 TI - Studies of the B-Z transition of DNA: The temperature dependence of the free energy difference, the composition of the counterion sheath in mixed salt, and the preparation of a sample of the 5'-d[T-(m(5) C-G)12 -T] duplex in pure B-DNA or Z-DNA form. AB - It is often envisioned that cations might coordinate at specific sites of nucleic acids and play an important structural role, for instance in the transition between B-DNA and Z-DNA. However, nucleic acid models explicitly devoid of specific sites may also exhibit features previously considered as evidence for specific binding. Such is the case of the "composite cylinder" (or CC) model which spreads out localized features of DNA structure and charge by cylindrical averaging, while sustaining the main difference between the B and Z structures, namely the better immersion of the B-DNA phosphodiester charges in the solution. Here, we analyze the non-electrostatic component of the free-energy difference between B-DNA and Z-DNA. We also compute the composition of the counterion sheath in a wide range of mixed-salt solutions and of temperatures: in contrast with the large difference of composition between the B-DNA and Z-DNA forms, the temperature dependence of sheath composition, previously unknown, is very weak. In order to validate the model, the mixed-salt predictions should be compared to experiment. We design a procedure for future measurements of the sheath composition based on Anomalous Small-Angle X-ray Scattering and complemented by (31) P NMR. With due consideration for the kinetics of the B-Z transition and for the capacity of generating at will the B or Z form in a single sample, the 5'-d[T (m(5) C-G)12 -T] 26-mer emerges as a most suitable oligonucleotide for this study. Finally, the application of the finite element method to the resolution of the Poisson-Boltzmann equation is described in detail. (c) 2016 Wiley Periodicals, Inc. Biopolymers 105: 369-384, 2016. PMID- 26900059 TI - Assessment of Itch and Pain in Animal Models and Human Subjects. AB - For the past century, scientists have developed a variety of methods to evaluate itch and pain in both animal models and human subjects to throw light on some of the most important pathways mediating these unpleasant sensations. Discoveries in the mechanisms underlying itch and pain in both physiological and pathological conditions relied greatly upon these studies and may eventually lead to the discovery of new therapeutics. However, it was a much more complicated job to access itch and pain in animal models than in human subjects due to the subjective nature of these sensations. The results could be contradictory or even misleading when applying different methodologies in animal models, especially under pathological conditions with a mixed sensation of itch and pain. This chapter introduces and evaluates some of the classical and newly designed methodologies to access the sensation of itch and pain in animal models as well as human subjects. PMID- 26900061 TI - Modulation of C-nociceptive Activities by Inputs from Myelinated Fibers. AB - To understand the mechanisms of neuropathic pain caused by demyelination, a rapid onset, completed but reversible demyelination of peripheral A-fibers and neuropathic pain behaviors in adult rats by single injection of cobra venom into the sciatic nerve, was created. Microfilament recording revealed that cobra venom selectively blocked A-fibers, but not C-fibers. Selective blockade of A-fibers may result from A-fiber demyelination at the site of venom injection as demonstrated by microscope examination. Neuropathic pain behaviors including inflammatory response appeared almost immediately after venom injection and lasted about 3 weeks. Electrophysiological studies indicated that venom injection induced loss of conduction in A-fibers, increased sensitivity of C-polymodal nociceptors to innocuous stimuli, and triggered spontaneous activity from peripheral and central terminals of C-fiber nociceptors. Neurogenic inflammatory responses were also observed in the affected skin via Evans blue extravasation experiments. Both antidromic C-fiber spontaneous activity and neurogenic inflammation were substantially decreased by continuous A-fiber threshold electric stimuli applied proximally to the venom injection site. The data suggest that normal activity of peripheral A-fibers may produce inhibitory modulation of C-polymodal nociceptors. Removal of inhibition to C-fiber polymodal nociceptors following demyelination of A-fibers may result in pain and neurogenic inflammation in the affected receptive field. PMID- 26900060 TI - Allergic Contact Dermatitis: A Model of Inflammatory Itch and Pain in Human and Mouse. AB - This chapter is an overview of published observations from our laboratory on the psychophysics and neurobiology of the persistent itch and pain of allergic contact dermatitis (ACD). ACD is a clinically significant problem with many features characteristic of other pruritic disorders. Our approach was to produce ACD experimentally in humans and in the mouse. The goal was to use the mouse as an animal model for investigating the peripheral neural mechanisms of itch and pain of ACD in humans. Humans and mice were each sensitized by cutaneous topical application of squaric acid dibutyl ester, a hapten not encountered in the environment. Subsequent challenge at another cutaneous site produced local inflammation ("ACD") with humans reporting persistent itch (lasting up to a week) and mice exhibiting persistent itch- and pain-like behaviors directed toward the ACD site. Enhanced mechanically evoked itch and pain in surrounding skin in humans were reversibly blocked by numbing the ACD site with cold, suggesting dependence on ongoing activity from the site. In mice, in vivo recordings revealed spontaneous activity in a subset of pruriceptive, mechanoheat-sensitive nociceptors with unmyelinated axons innervating the ACD site. These and a larger subpopulation of acutely dissociated small-diameter neurons innervating the ACD site exhibited an upregulation of the receptor CXCR3 and excitatory responses to one of its ligands, the chemokine CXCL10 (IP-10) that contributes to the pathogenesis of ACD. Preliminary findings point to possible therapeutic targets that could be investigated in inflammatory itch disorders in humans. PMID- 26900062 TI - New Mechanism of Bone Cancer Pain: Tumor Tissue-Derived Endogenous Formaldehyde Induced Bone Cancer Pain via TRPV1 Activation. AB - In recent years, our serial investigations focused on the role of cancer cells derived endogenous formaldehyde in bone cancer pain. We found that cancer cells produced formaldehyde through demethylation process by serine hydroxymethyltransferase (SHMT1 and SHMT2) and lysine-specific histone demethylase 1 (LSD1). When the cancer cells metastasized into bone marrow, the elevated endogenous formaldehyde induced bone cancer pain through activation on the transient receptor potential vanilloid subfamily member 1 (TRPV1) in the peripheral nerve fibers. More interestingly, TRPV1 expressions in the peripheral fibers were upregulated by the local insulin-like growth factor I (IGF-I) produced by the activated osteoblasts. In conclusion, tumor tissue-derived endogenous formaldehyde induced bone cancer pain via TRPV1 activation. PMID- 26900063 TI - Neuropathic Pain: Sensory Nerve Injury or Motor Nerve Injury? AB - Peripheral nerve injury often induces chronic neuropathic pain. Peripheral nerve is consisted of sensory fibers and motor fibers, it is questioned injury to which type of fibers is responsible for generation of neuropathic pain? Because neuropathic pain is sensory disorder, it is generally believed that the disease should be induced by injury to sensory fibers. In recent years, however, emergent evidence shows that motor fiber injury but not sensory fiber injury is necessary and sufficient for induction of neuropathic pain. Motor fiber injury leads to neuropathic pain by upregulating pro-inflammatory cytokines and brain-derived neurotrophic factor in pain pathway. PMID- 26900065 TI - Mas-Related G Protein-Coupled Receptors Offer Potential New Targets for Pain Therapy. AB - The founding member of the Mas-related G-protein-coupled receptor (Mrgpr) family was discovered in 1986. Since then, many more members of this receptor family have been identified in multiple species, and their physiologic functions have been investigated widely. Because they are expressed exclusively in small diameter primary sensory neurons, the roles of Mrgpr proteins in pain and itch have been best studied. This review will focus specifically on the current knowledge of their roles in pathological pain and the potential development of new pharmacotherapies targeted at some Mrgprs for the treatment of chronic pain. We will also discuss the limitations and future scope of this receptor family in pain treatment. PMID- 26900064 TI - Peripheral Nociceptors as Immune Sensors in the Development of Pain and Itch. AB - The peripheral nervous system and the immune system perform a series of similar functionalities such as recognizing, responding, and adapting to external or internal stimuli despite significant morphological differences. The peripheral nervous system actively communicates and coordinates with the immune system to function as a unified defense system. The peripheral nervous system is highly regulated by the immune system, especially under inflammatory conditions. On the other hand, the nervous system can modulate the immune system via neurotransmitters and chemokines released by the peripheral nerve endings, particularly from nociceptors. In both physiological and pathological conditions, peripheral nociceptive (including pruriceptive) neurons may express a variety of immune-related receptors, such as chemokine receptors and immunoglobulin (Fc) receptors that are usually found on immune cells. Certain ligands such as chemokines and immune complexes may induce abnormal neuronal hyperexcitability and even ectopic action potential discharges, therefore producing the sensation of pain and/or itch in immune-related diseases. The immune-sensing mechanisms of peripheral nociceptors may play an important role in the development of chronic pain and pruritus and may indicate novel therapeutic strategies for these pathological conditions. PMID- 26900066 TI - Pain Modulation and the Transition from Acute to Chronic Pain. AB - There is now increasing evidence that pathological pain states are at least in part driven by changes in the brain itself. Descending modulatory pathways are known to mediate top-down regulation of nociceptive processing, transmitting cortical and limbic influences to the dorsal horn. However, these modulatory pathways are also intimately intertwined with ascending transmission pathways through positive and negative feedback loops. Models of persistent pain that fail to include descending modulatory pathways are thus incomplete. Although teasing out individual links in a recurrent network is never straightforward, it is imperative that understanding of pain modulation be fully integrated into how we think about pain. PMID- 26900067 TI - Advances in the Treatment of Neuropathic Pain. AB - Neuropathic pain is pain that arises as a direct consequence of a lesion or diseases affecting the somatosensory system. Treatments for neuropathic pain include pharmacological, nonpharmacological, and interventional therapies. Currently recommended first-line pharmacological treatments include antidepressants and anticonvulsants (gabapentin and pregabalin). However, in some cases, pharmacological therapy alone fails to give adequate control of the chronic pain. New techniques have been invented and have been proved effective on neuropathic pain, such as behavioral, cognitive, integrative, and physical therapies. In this review, we focused on the advances in the treatment of central neuropathic pain, diabetic peripheral neuropathy, postherpetic neuralgia, and cancer pain. PMID- 26900068 TI - Integrated, Team-Based Chronic Pain Management: Bridges from Theory and Research to High Quality Patient Care. AB - Chronic pain is a significant public health concern. For many, chronic pain is associated with declines in physical functioning and increases in emotional distress. Additionally, the socioeconomic burden associated with costs of care, lost wages and declines in productivity are significant. A large and growing body of research continues to support the biopsychosocial model as the predominant framework for conceptualizing the experience of chronic pain and its multiple negative impacts. The model also informs a widely accepted and empirically supported approach for the optimal management of chronic pain. This chapter briefly articulates the historical foundations of the biopsychosocial model of chronic pain followed by a relatively detailed discussion of an empirically informed, integrated, multimodal and interdisciplinary treatment approach. The role of mental health professionals, especially psychologists, in the management of chronic pain is particularly highlighted. PMID- 26900070 TI - Vestibular function is associated with residual low-frequency hearing loss in patients with bi-allelic mutations in the SLC26A4 gene. AB - DFNB4 is non-syndromic, autosomal recessive type of hearing loss with an enlarged vestibular aqueduct (EVA) caused by mutations in SLC26A4/pendrin. Although the characteristics of hearing loss are well known in DFNB4, vestibular function remains inconclusive. We evaluated the vestibular function of 31 patients with bi allelic mutations in SLC26A4/pendrin and analyzed genetic, radiological, and audiological correlations with vestibular function. In a caloric test, unilateral and bilateral vestibulopathies were detected in 45.2% and 6.4% of patients, respectively; however, only 22.6% had subjective vertigo symptoms. While vestibular phenotype was not significantly associated with specific mutations in genetic alleles or the sizes of the endolymphatic sac and vestibular aqueduct, a residual hearing threshold at a low frequency (500 Hz) was definitely correlated with vestibular function in DFNB4 (p = 0.005). These findings may indicate that vestibular function in DFNB4 deteriorates unilaterally in ears when hearing loss occurs. In conclusion, DFNB4 shows vestibular dysfunction, which is strongly linked to hearing loss at low frequencies without any allelic or anatomical predisposing factor. PMID- 26900071 TI - Reply to: Psychometric properties of the Tinnitus Functional Index (TFI): Assessment in a UK research volunteer population. PMID- 26900069 TI - Using Functional Near Infrared Spectroscopy (fNIRS) to Study Dynamic Stereoscopic Depth Perception. AB - The parietal cortex has been widely implicated in the processing of depth perception by many neuroimaging studies, yet functional near infrared spectroscopy (fNIRS) has been an under-utilised tool to examine the relationship of oxy- ([HbO]) and de-oxyhaemoglobin ([HbR]) in perception. Here we examine the haemodynamic response (HDR) to the processing of induced depth stimulation using dynamic random-dot-stereograms (RDS). We used fNIRS to measure the HDR associated with depth perception in healthy young adults (n = 13, mean age 24). Using a blocked design, absolute values of [HbO] and [HbR] were recorded across parieto occipital and occipital cortices, in response to dynamic RDS. Control and test images were identical except for the horizontal shift in pixels in the RDS that resulted in binocular disparity and induced the percept of a 3D sine wave that 'popped out' of the test stimulus. The control stimulus had zero disparity and induced a 'flat' percept. All participants had stereoacuity within normal clinical limits and successfully perceived the depth in the dynamic RDS. Results showed a significant effect of this complex visual stimulation in the right parieto-occipital cortex (p < 0.01, eta(2) = 0.54). The test stimulus elicited a significant increase in [HbO] during depth perception compared to the control image (p < 0.001, 99.99 % CI [0.008-0.294]). The similarity between the two stimuli may have resulted in the HDR of the occipital cortex showing no significant increase or decrease of cerebral oxygenation levels during depth stimulation. Cerebral oxygenation measures of [HbO] confirmed the strong association of the right parieto-occipital cortex with processing depth perception. Our study demonstrates the validity of fNIRS to investigate [HbO] and [HbR] during high-level visual processing of complex stimuli. PMID- 26900072 TI - Anatomical and physiological development of the human inner ear. AB - We describe the development of the human inner ear with the invagination of the otic vesicle at 4 weeks gestation (WG), the growth of the semicircular canals from 5 WG, and the elongation and coiling of the cochlea at 10 WG. As the membranous labyrinth takes shape, there is a concomitant development of the sensory neuroepithelia and their associated structures within. This review details the growth and differentiation of the vestibular and auditory neuroepithelia, including synaptogenesis, the expression of stereocilia and kinocilia, and innervation of hair cells by afferent and efferent nerve fibres. Along with development of essential sensory structures we outline the formation of crucial accessory structures of the vestibular system - the cupula and otolithic membrane and otoconia as well as the three cochlea compartments and the tectorial membrane. Recent molecular studies have elaborated on classical anatomical studies to characterize the development of prosensory and sensory regions of the fetal human cochlea using the transcription factors, PAX2, MAF-B, SOX2, and SOX9. Further advances are being made with recent physiological studies that are beginning to describe when hair cells become functionally active during human gestation. This article is part of a Special Issue entitled . PMID- 26900073 TI - Musical experience sharpens human cochlear tuning. AB - The mammalian cochlea functions as a filter bank that performs a spectral, Fourier-like decomposition on the acoustic signal. While tuning can be compromised (e.g., broadened with hearing impairment), whether or not human cochlear frequency resolution can be sharpened through experiential factors (e.g., training or learning) has not yet been established. Previous studies have demonstrated sharper psychophysical tuning curves in trained musicians compared to nonmusicians, implying superior peripheral tuning. However, these findings are based on perceptual masking paradigms, and reflect engagement of the entire auditory system rather than cochlear tuning, per se. Here, by directly mapping physiological tuning curves from stimulus frequency otoacoustic emissions (SFOAEs)-cochlear emitted sounds-we show that estimates of human cochlear tuning in a high-frequency cochlear region (4 kHz) is further sharpened (by a factor of 1.5*) in musicians and improves with the number of years of their auditory training. These findings were corroborated by measurements of psychophysical tuning curves (PTCs) derived via simultaneous masking, which similarly showed sharper tuning in musicians. Comparisons between SFOAE and PTCs revealed closer correspondence between physiological and behavioral curves in musicians, indicating that tuning is also more consistent between different levels of auditory processing in trained ears. Our findings demonstrate an experience dependent enhancement in the resolving power of the cochlear sensory epithelium and the spectral resolution of human hearing and provide a peripheral account for the auditory perceptual benefits observed in musicians. Both local and feedback (e.g., medial olivocochlear efferent) mechanisms are discussed as potential mechanisms for experience-dependent tuning. PMID- 26900074 TI - Avoiding complications in gynecological minimal-access surgery. PMID- 26900075 TI - The challenges associated with molecular targeted therapies for glioblastoma. AB - Glioblastoma (GBM) is the most aggressive malignant brain tumor in adults. Improvements in the treatment of GBM have remained static since the advent of the standard therapy which includes radiation with concurrent and adjuvant temozolomide treatment. Developing treatment and diagnostic or companion biomarker combinations is transforming the way we treat numerous cancers. However, can this emerging paradigm be also effective for GBM? Can GBM be treated the same way as other cancers? Here we review the challenges for a personalized molecular targeted therapeutic approach in GBM. The specific challenges for establishing a personalized molecular targeted medicine program for GBM patients include overcoming the blood brain barrier, unravelling the intra- and inter heterogeneity that exists and the importance of developing more relevant animal models that recapitulate a patient's GBM tumor. PMID- 26900076 TI - Posterior reversible encephalopathy syndrome in cancer patients: a single institution retrospective study. AB - Posterior reversible encephalopathy syndrome (PRES) is a clinico-radiologic entity. Its management and outcome in the oncology population is limited because it is still difficult to identify despite an increasingly recognized occurrence. This is the largest retrospective study of PRES in cancer patients reported from a single institution. We explore the clinical manifestations and radiologic features to comprehensively assess PRES in order to prevent permanent neurologic deficits and mortality. We retrospectively identified 69 patients with cancer who developed PRES at MDACC between 01/2006 to 06/2012. Clinical and radiographic data were abstracted from their records and reviewed for our analysis. Mean age at PRES onset was 52 +/- 17.8 years. Fifty-two (75 %; p < 0.001) patients were women. Most common diagnoses were leukemia (30 %) and lymphoma (12 %). Forty eight (70 %) patients were treated with chemotherapy, 21 (30 %) bone marrow transplant and 14 (20 %) tacrolimus. Most common clinical presentation was seizures (67 %). PRES was associated with hypertension in 62 (90 %) patients. On brain MRI, 33 (44 %) patients had some evidence of hemorrhage, 22 (73 %) of these were thrombocytopenic. Thirty-five (51 %) patients fully recovered and 19 (28 %) had permanent neurological deficits. Morbidity and mortality were associated with continuation with offending agent, thrombocytopenia, variations in mean arterial pressure >=20 mmHg, electrographic seizures at onset, atypical MRI pattern and delay in diagnostic imaging (7.4 +/- 4.8 days vs. 1.9 +/- 1.8 days; p = 0.031) as half of them did not receive a prompt intervention. Special attention should be given to patients who present with high-risk factors in order to prevent development of PRES or decrease patient morbidity and mortality. Management of PRES should be guided by the radiographic findings. Overall, early recognition, discontinuation of the offending agents, correction of thrombocytopenia and blood pressure control are still the main strategies to manage PRES. PMID- 26900077 TI - Pro-apoptotic and anti-angiogenic properties of the alpha /beta-thujone fraction from Thuja occidentalis on glioblastoma cells. AB - The most aggressive type of brain tumor is glioblastoma multiforme, which to date remains incurable. Thuja occidentalis is used in homeopathy for the treatment of cancer, however, its mechanism of action remains unknown. We set out to study the effects of thujone fractions of Thuja on glioblastoma using in vitro and in vivo models. We found that the alpha/ beta-thujone fraction decrease the cell viability and exhibit a potent anti-proliferative, pro-apoptotic and anti angiogenic effects in vitro. In vivo assays showed that alpha /beta-thujone promotes the regression of neoplasia and inhibits the angiogenic markers VEGF, Ang-4 and CD31 into the tumor. PMID- 26900080 TI - Genetics-directed drug discovery for combating Mycobacterium tuberculosis infection. AB - Mycobacterium tuberculosis (Mtb), the pathogen of tuberculosis (TB), is one of the most infectious bacteria in the world. The traditional strategy to combat TB involves targeting the pathogen directly; however, the rapid evolution of drug resistance lessens the efficiency of this anti-TB method. Therefore, in recent years, some researchers have turned to an alternative anti-TB strategy, which hinders Mtb infection through targeting host genes. In this work, using a theoretical genetic analysis, we identified 170 Mtb infection-associated genes from human genetic variations related to Mtb infection. Then, the agents targeting these genes were identified to have high potential as anti-TB drugs. In particular, the agents that can target multiple Mtb infection-associated genes are more druggable than the single-target counterparts. These potential anti-TB agents were further screened by gene expression data derived from connectivity map. As a result, some agents were revealed to have high interest for experimental evaluation. This study not only has important implications for anti TB drug discovery, but also provides inspirations for streamlining the pipeline of modern drug discovery. PMID- 26900079 TI - Comparing the discriminative stimulus effects of modulators of GABAA receptors containing alpha4-delta subunits with those of gaboxadol in rats. AB - RATIONALE: Gaboxadol is a selective agonist at gamma-aminobutyric acidA (GABAA) receptors that contain alpha4-delta subunits, and it produces anxiolytic and sedative effects. Although adverse effects preclude its clinical use, its mechanism of action suggests that those receptors might provide novel therapeutic targets, particularly for modulators of those GABAA receptor subtypes, by retaining therapeutic effects of gaboxadol and not adverse effects. OBJECTIVES: The current study compared discriminative stimulus effects of gaboxadol with those of modulators acting at GABAA receptors containing alpha4-delta subunits. MATERIALS: Eight rats discriminated 5.6 mg/kg gaboxadol from vehicle while responding under a fixed - ratio 10 schedule for food. Modulators acting at GABAA receptors containing alpha4-delta subunits (pregnanolone, ethanol, and flumazenil) and receptors that do not contain those subunits (midazolam) were studied alone; pregnanolone and ethanol were also combined with gaboxadol. In addition, gaboxadol was studied in separate groups discriminating 0.32 mg/kg midazolam, 3.2 mg/kg pregnanolone, or 0.75 g/kg ethanol from vehicle. RESULTS: Gaboxadol produced >=80 % gaboxadol-lever responding and did not alter rates. No other drug produced, on average, >=80 % drug-lever responding up to doses that decreased rates, although 1.78 mg/kg midazolam produced 32 % gaboxadol-lever responding. Ethanol and pregnanolone did not enhance the effects of gaboxadol. Rats discriminating midazolam, pregnanolone, or ethanol from vehicle responded predominantly on the vehicle lever after receiving gaboxadol. CONCLUSIONS: Drugs that modulate GABAA receptors containing alpha4-delta subunits neither mimicked nor enhanced the discriminative stimulus effects of gaboxadol, indicating that at least some effects of gaboxadol are not shared with modulators of that GABAA receptor subtype. PMID- 26900081 TI - MRP1 mediates folate transport and antifolate sensitivity in Plasmodium falciparum. AB - Multidrug resistance-associated proteins (MRP) of Plasmodium falciparum have been associated with altered drug sensitivity. Knowledge on MRP substrate specificity is indispensible for the characterization of resistance mechanisms and identifying its physiological roles. An untargeted metabolomics approach detected decreased folate concentrations in red blood cells infected with schizont stage parasites lacking expression of MRP1. Furthermore, a tenfold decrease in sensitivity toward the folate analog methotrexate was detected for parasites lacking MRP1. PfMRP1 is involved in the export of folate from parasites into red blood cells and is therefore a relevant factor for efficient malaria treatment through the folate pathway. PMID- 26900078 TI - An investigation into aripiprazole's partial D2 agonist effects within the dorsolateral prefrontal cortex during working memory in healthy volunteers. AB - RATIONALE: Working memory impairments in schizophrenia have been attributed to dysfunction of the dorsolateral prefrontal cortex (DLPFC) which in turn may be due to low DLPFC dopamine innervation. Conventional antipsychotic drugs block DLPFC D2 receptors, and this may lead to further dysfunction and working memory impairments. Aripiprazole is a D2 receptor partial agonist hypothesised to enhance PFC dopamine functioning, possibly improving working memory. OBJECTIVES: We probed the implications of the partial D2 receptor agonist actions of aripiprazole within the DLPFC during working memory. Investigations were carried out in healthy volunteers to eliminate confounds of illness or medication status. Aripiprazole's prefrontal actions were compared with the D2/5-HT2A blocker risperidone to separate aripiprazole's unique prefrontal D2 agonist actions from its serotinergic and striatal D2 actions that it shares with risperidone. METHOD: A double-blind, placebo-controlled, parallel design was implemented. Participants received a single dose of either 5 mg aripiprazole, 1 mg risperidone or placebo before performing the n-back task whilst undergoing fMRI scanning. RESULTS: Compared with placebo, the aripiprazole group demonstrated enhanced DLPFC activation associated with a trend for improved discriminability (d') and speeded reaction times. In contrast to aripiprazole's neural effects, the risperidone group demonstrated a trend for reduced DLPFC recruitment. Unexpectedly, the risperidone group demonstrated similar effects to aripiprazole on d' and additionally had reduced errors of commission compared with placebo. CONCLUSION: Aripiprazole has unique DLPFC actions attributed to its prefrontal D2 agonist action. Risperidone's serotinergic action that results in prefrontal dopamine release may have protected against any impairing effects of its prefrontal D2 blockade. PMID- 26900082 TI - TRPM7 channel regulates ox-LDL-induced proliferation and migration of vascular smooth muscle cells via MEK-ERK pathways. AB - Transient receptor potential melastatin 7 (TRPM7) plays a key role in the pathophysiological response of multiple cell types. However, the role of TRPM7 channels in ox-LDL-induced proliferation and migration of VSMC remains unclear. This study used the thoracic aorta VSMCs to explore the effects of ox-LDL on cell proliferation and migration and to investigate the underlying molecular mechanisms and signaling pathways. Data demonstrated that ox-LDL significantly increased TRPM7 activity, and induced VSMC proliferation and migration. VSMC proliferation and migration were inhibited by nonspecific TRPM7 blocker 2-APB or synthetic siRNA targeting TRPM7. Furthermore, the phosphorylation of ERK1/2 and MEK1/2 associated with cell proliferation and migration decreased in TRPM7 deficient VSMC. Therefore, TRPM7 may constitute a useful target for the treatment of atherosclerosis. PMID- 26900083 TI - Friend or foe? Biological and ecological traits of the European ash dieback pathogen Hymenoscyphus fraxineus in its native environment. AB - Hymenoscyphus fraxineus, an introduced ascomycete fungus and primary causal agent of European ash dieback, was investigated on Fraxinus mandshurica trees in its native range in Primorye region of Far East Russia. This evidence is the first report of H. fraxineus on healthy, asymptomatic F. mandshurica trees. High throughput sequencing revealed 49 distinct fungal taxa associated with leaves of F. mandshurica, 12 of which were identified to species level. Phyllosphere fungal assemblages were similar among sites despite being largely geographically distant. Many organisms comprising the foliar fungal community on F. mandshurica in Far East Russia have similarity to those reported inhabiting F. excelsior in Europe based on previous studies. However, Mycosphaerella sp., the most dominant species in this study and detected in nearly all samples, was associated only with F. mandshurica. Genetic diversity of H. fraxineus was significantly higher in the Far East Russian population than in Europe. In contrast to its aggressive behaviour on Fraxinus excelsior in Europe, H. fraxineus appears to be a benign associate of indigenous F. mandshurica that initially induces quiescent and asymptomatic infections in healthy trees prior to active host colonization normally associated with modification of host tissue during senescence. PMID- 26900084 TI - Impact of Gut Colonization by Antibiotic-Resistant Bacteria on the Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation: A Retrospective, Single Center Study. AB - Gut colonization by antibiotic-resistant bacteria may underlie hard-to-treat systemic infections. There is also accumulating evidence on the immunomodulatory function of gut microbiota after allogeneic stem cell transplantation (alloSCT) and its impact on graft-versus-host disease (GVHD). We investigated the epidemiology and clinical impact of gut colonization after alloSCT and retrospectively analyzed data on 107 alloSCTs performed at a single transplant center. Pretransplant microbiology screening identified colonization in 31% of cases. Colonization had a negative impact on overall survival after alloSCT in univariate (34% versus 74% at 24 months, P < .001) and multivariate (hazard ratio, 3.53; 95% confidence interval, 1.71 to 7.28; P < .001) analyses. Nonrelapse mortality was significantly higher in colonized than in noncolonized patients (42% versus 11% at 24 months, P = .001). Colonized patients more frequently experienced bacteremia (48% versus 24%, P = .01), and more deaths were attributable to infectious causes in the colonized group (42% versus 11% of patients and 67% versus 29% of deaths, P < .05). We observed a significantly higher incidence of grades II to IV acute GVHD in colonized than in noncolonized patients (42% versus 23%, P < .05), especially involving the gastrointestinal system (33% versus 13.5%, P = .07). In summary, we determined that gut colonization by antibiotic-resistant bacteria decreases the overall survival of patients undergoing alloSCT by increasing nonrelapse mortality and the incidences of systemic infection and acute GVHD. PMID- 26900085 TI - Two different genetic diseases in the same patient: Coincident, concomitant, or causally related? PMID- 26900086 TI - On the causal structure between CO2 and global temperature. AB - We use a newly developed technique that is based on the information flow concept to investigate the causal structure between the global radiative forcing and the annual global mean surface temperature anomalies (GMTA) since 1850. Our study unambiguously shows one-way causality between the total Greenhouse Gases and GMTA. Specifically, it is confirmed that the former, especially CO2, are the main causal drivers of the recent warming. A significant but smaller information flow comes from aerosol direct and indirect forcing, and on short time periods, volcanic forcings. In contrast the causality contribution from natural forcings (solar irradiance and volcanic forcing) to the long term trend is not significant. The spatial explicit analysis reveals that the anthropogenic forcing fingerprint is significantly regionally varying in both hemispheres. On paleoclimate time scales, however, the cause-effect direction is reversed: temperature changes cause subsequent CO2/CH4 changes. PMID- 26900087 TI - Costs of fear: behavioural and life-history responses to risk and their demographic consequences vary across species. AB - Behavioural responses to reduce predation risk might cause demographic 'costs of fear'. Costs differ among species, but a conceptual framework to understand this variation is lacking. We use a life-history framework to tie together diverse traits and life stages to better understand interspecific variation in responses and costs. We used natural and experimental variation in predation risk to test phenotypic responses and associated demographic costs for 10 songbird species. Responses such as increased parental attentiveness yielded reduced development time and created benefits such as reduced predation probability. Yet, responses to increased risk also created demographic costs by reducing offspring production in the absence of direct predation. This cost of fear varied widely across species, but predictably with the probability of repeat breeding. Use of a life history framework can aid our understanding of potential demographic costs from predation, both from responses to perceived risk and from direct predation mortality. PMID- 26900088 TI - The Alba protein family: Structure and function. AB - Alba family proteins are small, basic, dimeric nucleic acid-binding proteins, which are widely distributed in archaea and a number of eukaryotes. This family of proteins bears the distinct features of regulation through acetylation/deacetylation, hence named as acetylation lowers binding affinity (Alba). Alba family proteins bind DNA cooperatively with no apparent sequence specificity. Besides DNA, Alba proteins also interact with diverse RNA species and associate with ribonucleo-protein complexes. Initially, Alba proteins were recognized as chromosomal proteins and supposed to be involved in the maintenance of chromatin architecture and transcription repression. However, recent studies have shown increasing evidence of functional plasticity among Alba family of proteins that widely range from genome packaging and organization, transcriptional and translational regulation, RNA metabolism, and development and differentiation processes. In recent years, Alba family proteins have attracted growing interest due to their widespread occurrence in large number of organisms. Presence in multiple copies, functional crosstalk, differential binding affinity, and posttranslational modifications are some of the key factors that might regulate the biological functions of Alba family proteins. In this review article, we present an overview of the Alba family proteins, their salient features and emphasize their functional role in different organisms reported so far. PMID- 26900089 TI - Prognostic value of diffusion-weighted magnetic resonance imaging and 18F fluorodeoxyglucose-positron emission tomography/computed tomography after concurrent chemoradiotherapy in uterine cervical cancer. AB - PURPOSE: To evaluate the prognostic value of diffusion-weighted imaging (DWI) and positron emission tomography/computed tomography (PET/CT) for predicting disease progression after concurrent chemoradiotherapy (CCRT) in cervical cancer. MATERIALS AND METHODS: A total of 67 locally advanced cervical cancer patients who received CCRT underwent both DWI and PET/CT before and during (at 1month) treatment. The mean apparent diffusion coefficient (ADCmean) and maximum standardized uptake value (SUVmax) were measured on the tumor and the percentage changes between 2 time points (DeltaADCmean and DeltaSUVmax) were calculated. The DeltaADCmean and DeltaSUVmax were compared in terms of predicting disease progression after CCRT. RESULTS: During a mean follow-up of 2.7years, disease progression was identified in 16 patients (23.9%). The DeltaADCmean and DeltaSUVmax were significantly correlated (Spearman correlation coefficient, 0.38; P=0.002). For predicting disease progression, the integrated area under the curves of DeltaADCmean (0.791) and DeltaSUVmax (0.781) were not significantly different (P=0.88). On multivariate analysis, both DeltaADCmean and DeltaSUVmax were the independent predictors of disease progression (hazard ratio, 7.9 and 8.7; P, 0.001 and <0.001, respectively). CONCLUSION: The percentage changes of ADCmean and SUVmax during CCRT have a similar prognostic value for predicting disease progression after CCRT in cervical cancers. PMID- 26900090 TI - Dose escalation to dominant intraprostatic lesions with MRI-transrectal ultrasound fusion High-Dose-Rate prostate brachytherapy. Prospective phase II trial. AB - BACKGROUND AND PURPOSE: To demonstrate the feasibility, safety and effectiveness of dose escalation to intraprostatic lesions with MRI-transrectal ultrasound fusion High-Dose-Rate (HDR) brachytherapy. MATERIALS AND METHODS: 15 patients with intermediate-high risk prostate cancer and visible dominant intra-prostatic nodule on mpMRI have been treated. The treatment consisted of combined MRI-TRUS fusion HDR-brachytherapy (1 fraction of 1500cGy) and hypofractionated external beam (3750cGy in 15 fractions). A dose of 1875Gy was delivered to at least 98% of the DIL volume. RESULTS: Median prostate volume was 23.8cc; median number of needles was 16 (13-18). Dose escalation to DIL was feasible in 14/15 patients (93%) without violating dosimetric constraints and 1 patient presented a minimal deviation of dosimetric restrictions. With a median follow-up of 18months (17 24), none of the patients developed acute urinary retention or grade ?3 toxicity. In addition to standard PSA follow-up, response has been assessed by mpMRI at 12months. All patients presented adequate morphological responses on anatomical and functional sequences. CONCLUSIONS: HDR brachytherapy using MRI-transrectal ultrasound fusion for image guidance is a suitable technique for partial prostate dose escalation. Tolerance and toxicity profiles are excellent and results are encouraging in terms of biochemical, morphological and functional response. PMID- 26900091 TI - Long-term follow-up of patients with locally advanced non-small cell lung cancer receiving concurrent hypofractionated chemoradiotherapy with or without cetuximab. AB - BACKGROUND AND PURPOSE: Radiation dose escalation using hypofractionation might improve overall survival (OS). We investigated OS in a phase II multicenter study in locally advanced non-small cell lung cancer (LA-NSCLC) patients treated with hypofractionated concurrent chemoradiotherapy. MATERIALS AND METHODS: A 2-armed phase II, multi-center study (NTR2230) was performed with the aim to assess the effect of cetuximab to concurrent chemoradiotherapy in LA-NSCLC patients (stage II/IIIA/B). Arm A received high dose radiotherapy (24 * 2.75 Gy) and concurrent daily low-dose cisplatin (6 mg/m(2)). Arm B received an identical treatment regimen with additional weekly cetuximab. Kaplan-Meier survival curves and 1-, 2- and 5-year OS proportions were calculated. RESULTS: Between February 2009 and May 2011, 102 patients were randomly allocated in two arms. Median OS was 31.5 months (range 12.8-52.3), not significantly different between arms A and B; 33.0 (range 17.0-57.0) and 30.0 (11.0-52.0) months. 1-, 2- and 5-year OS rates were 74.5%, 59.4% and 37.3%, respectively. In multivariate analyses, worse performance score, V35 of the esophagus and the existence of comorbidities were significantly (P value<0.05) associated with a shorter OS. DISCUSSION: In this phase II trial, the median OS for the entire group was remarkably high; 31.5 months. Furthermore, 5 year OS was still 37.3%. Hypofractionation might contribute to improved OS in LA NSCLC patients. PMID- 26900092 TI - Differential analysis of local and regional failure in locally advanced non-small cell lung cancer patients treated with concurrent chemoradiotherapy. AB - BACKGROUND AND PURPOSE: Concurrent chemoradiotherapy (CCRT) is the standard treatment in locally advanced non-small cell lung cancer (NSCLC) patients. In clinical practice, the primary tumor (PT) and involved lymph nodes (LNs) receive the same radiotherapy dose. This study investigates differences between local failure (LF) and regional failure (RF). MATERIAL AND METHODS: Patients were irradiated with 66 Gy in 24 fractions (using IMRT) combined with daily low dose cisplatin. The PT and LNs were contoured on the planning CT-scan registered with a (18)FDG-PET-scan. Log10(Volume) and SUVmax of PT and LNs, location (LNs versus PT), performance status, age and gender were tested as prognostic factors for lesion failure using cox regression analysis. RESULTS: In total, 226 patients were analyzed. LF or RF as first event was seen in 37 PT (16%) and 14 LNs (6%). Log10(Volume), location and SUVmax were significantly associated with failure in univariate analysis. In multivariate analysis, only log10(Volume) remained as a significant factor. CONCLUSIONS: A LF and RF as first event of respectively 16% and 6% were observed in locally advanced NSCLC patients treated with CCRT. This difference was primarily associated with the difference in log10(Volume) of the primary tumor and lymph nodes. PMID- 26900093 TI - Automated daily breath hold stability measurements by real-time imaging in radiotherapy of breast cancer. AB - BACKGROUND AND PURPOSE: Breath hold is increasingly used for cardiac sparing in left-sided breast cancer irradiation. We have developed a fast automated method to verify breath hold stability in each treatment fraction. MATERIAL AND METHODS: We evaluated 504 patients treated with breath hold. Moderate deep inspiration breath hold was audio-guided. Medial and lateral large tangential field segments were delivered in a single breath hold and movieloops of these fields were acquired with an EPID. The thoracic wall position was automatically detected in each frame and the full range of thoracic wall motion (RTWM) was determined. If the RTWM >4mm more than 3 times, the patient was excluded from breath hold treatment if further coaching did not yield improvement. RESULTS: Unstable breath hold was observed in 2.8% of the patients. However, this frequency dropped from 9.5% in the first 6months to 1.6% in the subsequent 16months. The 97% of patients with proper breath hold showed excellent stability: the average RTWM was 0.9+/ 0.5mm. The reproducibility of the breath hold depth was confirmed by (1) the small difference between the thoracic wall positions in the medial and lateral fields within one fraction and (2) the setup errors of breath hold patients showed no significant differences with those of right-sided breast patients. CONCLUSIONS: We have developed and clinically applied an imaging tool to automatically determine stability of breath holds in each treatment fraction during beam delivery. PMID- 26900094 TI - Bone marrow derived macrophages fuse with intestine stromal cells and contribute to chronic fibrosis after radiation. AB - BACKGROUND AND PURPOSE: Bone marrow-derived cells (BMDC) have been demonstrated to play a critical role in intestine regeneration. However, organ fibrosis was one of the major side effects of bone marrow (BM) transplantation. It warrants further investigation on the mechanisms of BM cell therapy in radiation induced intestine damage. MATERIALS AND METHODS: We established three murine models to evaluate BMDC within intestines after radiation, including cre-loxP system of transgenic mice. In vitro co-culture between murine BM with human intestine stromal cells was also performed to measure the level of fusion and fibrosis after treatment with anti-fibrotic agents or after macrophage depletion. RESULTS: Despite complete recovery of epithelial mucosa from radiation damage, we found persistent proliferation and repopulation of BMDC within the lamina propria. Fusion between BM derived monocytic and intestine stromal cells correlated with the level of fibrosis and proliferation index. Depleting macrophages genetically using CD11b-DTR mouse model or pharmacologically using clodronate liposome reduced the level of cell fusion and intestine fibrosis. CONCLUSIONS: Fibrotic cues from intestine enhance fusion between BM-derived monocytes/macrophages with intestine stromal cells. The fusion hybrids promote cell cycle re-entry, proliferation and reinforce fibrosis signal. Depleting macrophages interferes with cell fusion and ameliorates radiation-induced intestine fibrosis. PMID- 26900095 TI - Guidelines for endoscopic management of non-variceal upper gastrointestinal bleeding. AB - Japan Gastroenterological Endoscopy Society (JGES) has compiled a set of guidelines for endoscopic management of non-variceal upper gastrointestinal bleeding using evidence-based methods. The major cause of non-variceal upper gastrointestinal bleeding is peptic gastroduodenal ulcer bleeding. As a result, these guidelines mainly focus on peptic gastroduodenal ulcer bleeding, although bleeding from other causes is also overviewed. From the epidemiological aspect, in recent years in Japan, bleeding from drug-related ulcers has become predominant in comparison with bleeding from Helicobacter pylori (HP)-related ulcers, owing to an increase in the aging population and coverage of HP eradication therapy by national health insurance. As for treatment, endoscopic hemostasis, in which there are a variety of methods, is considered to be the first-line treatment for bleeding from almost all causes. It is very important to precisely evaluate the severity of the patient's condition and stabilize the patient's vital signs with intensive care for successful endoscopic hemostasis. Additionally, use of antisecretory agents is recommended to prevent rebleeding after endoscopic hemostasis, especially for gastroduodenal ulcer bleeding. Eighteen statements with evidence and recommendation levels have been made by the JGES committee of these guidelines according to evidence obtained from clinical research studies. However, some of the statements that are supported by a low level of evidence must be confirmed by further clinical research. PMID- 26900096 TI - [Pictocam instead of Pictogram - a quality improvement study in abdominal ultrasound imaging]. AB - AIM: To replace pictograms with pictocam pictures: A prospective blinded quality improvement study in documenting image orientation and localisation in abdominal ultrasound imaging. MATERIALS AND METHODS: A minicam was mounted on the ultrasound scanhead to record pictocam pictures. The primary examiner produced an ultrasound image together with the routinely embedded pictogram. Subsequently the pictogram was covered by the synchronically taken pictocam picture. Subsequently, the primary examiner assessed the pictograms and the second examiner the pictocam pictures (blinded to the pictogram findings of the primary examiner). RESULTS: A total of 679 paired pictogram and pictocam pictures were available from 114 patients. The localisation of the utrasound head showed an absolute or close agreement of 99.7% (677/679) with a 95% confidence interval of [98.94%-99.96%]. The angle of the ultrasound head showed an absolute or close agreement of 99.0% (672/679) with a 95% confidence interval of [97.98% - 99.58%]. CONCLUSION: This study shows that the pictogram can validely be replaced by a pictocam picture. The routine addition of a minicam to the ultrasound scanhead would thus not only improve the quality of the documentation, but would also result in time savings during examinations. PMID- 26900097 TI - Evaluation of biomarkers for the prediction of pre-eclampsia in women with type 1 diabetes mellitus: A systematic review. AB - BACKGROUND: Pre-eclampsia is a leading cause of maternal and perinatal morbidity and mortality. Women with type 1 diabetes are considered a high-risk group for developing pre-eclampsia. Much research has focused on biomarkers as a means of screening for pre-eclampsia in the general maternal population; however, there is a lack of evidence for women with type 1 diabetes. OBJECTIVES: To undertake a systematic review to identify potential biomarkers for the prediction of pre eclampsia in women with type 1 diabetes. SEARCH STRATEGY: We searched Medline, EMBASE, Maternity and Infant Care, Scopus, Web of Science and CINAHL SELECTION CRITERIA: Studies were included if they measured biomarkers in blood or urine of women who developed pre-eclampsia and had pre-gestational type 1 diabetes mellitus Data collection and analysis A narrative synthesis was adopted as a meta analysis could not be performed, due to high study heterogeneity. MAIN RESULTS: A total of 72 records were screened, with 21 eligible studies being included in the review. A wide range of biomarkers was investigated and study size varied from 34 to 1258 participants. No single biomarker appeared to be effective in predicting pre-eclampsia; however, glycaemic control was associated with an increased risk while a combination of angiogenic and anti-angiogenic factors seemed to be potentially useful. CONCLUSIONS: Limited evidence suggests that combinations of biomarkers may be more effective in predicting pre-eclampsia than single biomarkers. Further research is needed to verify the predictive potential of biomarkers that have been measured in the general maternal population, as many studies exclude women with diabetes preceding pregnancy. PMID- 26900098 TI - Oral antidiabetics use among diabetic type 2 patients with chronic kidney disease. Do nephrologists take account of recommendations? AB - BACKGROUND: There is an increasing prevalence of diabetes type 2 and chronic kidney disease, challenging appropriate prescribing of oral anti-diabetic drugs (OADs). METHODS: We have described the practice patterns of 13 nephrologists in 4 centers, in a cohort of 301 consecutive adult type 2 diabetic patients. Among oral anti-diabetic prescriptions, we have detailed drugs dosage for each subject, with 3 different formulae for estimating glomerular filtration rate (GFR) and its adequation according to the latest ERBP recommendations (2015). As individuals were mostly obese in this work, we also compare adequacy rates using both standard indexed CKD-EPI formula and CKD-EPI formula de-indexed from body surface area. RESULTS: Using the CKD-EPI formula as the reference method for estimating GFR, 53.5% of patients were outside the recommendations, mostly for metformin (30% of the whole cohort) and for sitagliptin (17.9% of the whole cohort). With Cockcroft and Gault formula, 38.2% of persons were outside recommendations and 45.9% (p<0.001) with CKD-EPI de-indexed. Among individuals consulting a nephrologist for the first time (n=90), 61.1% were outside recommendations (p=0.1). Among those persons under diabetologist supervision (n=103), 63.1% were outside recommendations (p=0.09), and were taking significantly more often metformin and insulin. CONCLUSION: We have found a substantial number of inadequate OAD prescriptions in type 2 diabetic patients with chronic kidney disease. The proportion of individuals outside guidelines was strongly affected by the method used for estimating GFR and by the type of practice, i.e., specialists versus general practitioners. PMID- 26900099 TI - Impact of a community-based exercise programme on physical fitness in middle-aged and older patients with type 2 diabetes. AB - OBJECTIVES: Physical fitness is related to all-cause mortality, quality of life and risk of falls in patients with type 2 diabetes. This study aimed to analyse the impact of a long-term community-based combined exercise program (aerobic+resistance+agility/balance+flexibility) developed with minimum and low cost material resources on physical fitness in middle-aged and older patients with type 2 diabetes. METHODS: This was a non-experimental pre-post evaluation study. Participants (N=43; 62.92+/-5.92 years old) were engaged in a community based supervised exercise programme (consisting of combined aerobic, resistance, agility/balance and flexibility exercises; three sessions per week; 70min per session) of 9 months' duration. Aerobic fitness (6-Minute Walk Test), muscle strength (30-Second Chair Stand Test), agility/balance (Timed Up and Go Test) and flexibility (Chair Sit and Reach Test) were assessed before (baseline) and after the exercise intervention. RESULTS: Significant improvements in the performance of the 6-Minute Walk Test (Delta=8.20%, p<0.001), 30-Second Chair Stand Test (Delta=28.84%, p<0.001), Timed Up and Go Test (Delta=14.31%, p<0.001), and Chair Sit and Reach Test (Delta=102.90%, p<0.001) were identified between baseline and end-exercise intervention time points. CONCLUSIONS: A long-term community-based combined exercise programme, developed with low-cost exercise strategies, produced significant benefits in physical fitness in middle-aged and older patients with type 2 diabetes. This supervised group exercise programme significantly improved aerobic fitness, muscle strength, agility/balance and flexibility, assessed with field tests in community settings. PMID- 26900100 TI - [Length of stay in patients admitted for acute heart failure]. AB - OBJECTIVE: To identify the factors associated with prolonged length of hospital stay in patients admitted for acute heart failure. METHODS: Multipurpose observational cohort study including patients from the EAHFE registry admitted for acute heart failure in 25 Spanish hospitals. Data were collected on demographic and clinical variables and on the day and place of admission. The primary outcome was length of hospital stay longer than the median. RESULTS: We included 2,400 patients with a mean age of 79.5 (9.9) years; of these, 1,334 (55.6%) were women. Five hundred and ninety (24.6%) were admitted to the short stay unit (SSU), 606 (25.2%) to cardiology, and 1,204 (50.2%) to internal medicine or gerontology. The mean length of hospital stay was 7.0 (RIC 4-11) days. Fifty-eight (2.4%) patients died and 562 (23.9%) were readmitted within 30 days after discharge. The factors associated with prolonged length of hospital stay were chronic pulmonary disease; being a device carrier; having an unknown or uncommon triggering factor; the presence of renal insufficiency, hyponatremia and anaemia in the emergency department; not being admitted to an SSU or the lack of this facility in the hospital; and being admitted on Monday, Tuesday or Wednesday. The factors associated with length of hospital stay<=7days were hypertension, having a hypertensive episode, or a lack of treatment adherence. The area under the curve of the mixed model adjusted to the center was 0.78 (95% CI: 0.76-0.80; p<0.001). CONCLUSIONS: A series of factors is associated with prolonged length of hospital stay and should be taken into account in the management of acute heart failure. PMID- 26900101 TI - [Use of customer relationship management to improve healthcare for citizens. The 24h Andalusian Health Service: Healthline]. AB - Salud Responde (in English: Healthline) is a Health Service and Information Centre of the taxpayer-funded Andalusian Health System (AHS) that offers a Telephone Health Advisory Service called SA24h, among other services. The main objective of SA24h is to inform and advise citizens on health issues and the available health resources of the AHS. SA24h has a Customer Relationship Management information technology tool that organises information at various levels of specialization. Depending on the difficulty of the query, the citizen is attended by professionals with distinct profiles, providing a consensual response within the professionals working within Salud Responde or within other healthcare levels of the AHS. SA24h provided responses to 757,168 patient queries from late 2008 to the end of 01/12/2015. A total of 9.38% of the consultations were resolved by the non-health professionals working at Salud Responde. The remaining 84.07% were resolved by health staff. A total of 6.5% of users were referred to accident and emergency facilities while 88.77% did not need to attend their general practitioner within the next 24hours, thus avoiding unnecessary visits to health care facilities. PMID- 26900102 TI - [The transition process from paediatric to adult services: A perspective from hospitalised adolescent sufferers of chronic diseases]. AB - INTRODUCTION: Chronic illnesses during adolescence are a big challenge for the patient, his or her family, and health care providers. The transition from paediatric health services to adult health services involves a programmed and planned transfer process of adolescent sufferers of chronic illnesses, in order to maintain a high quality of life and bio-psycho-social development. There is currently no transition model. The objective of the study is to understand the transition process from the perspective of hospitalised adolescents to collaborate towards the design of a model that meets the needs studied. PATIENTS AND METHOD: Semi-structured interviews with 13 adolescent sufferers of chronic illnesses, hospitalised in two healthcare centres in Santiago, Chile, in one analytical-relational study, supported by qualitative methodology. RESULTS: In the analysis, 5 major themes stand out: experience of living with the illness, the importance of the doctor-patient relationship, the concept of limited autonomy to the pharmacology, the absence of the transition process as such, and the identification of barriers and needs for an adequate transition. CONCLUSIONS: This study is new in Chile in that it explores the phenomenom of the transition of adolescents with chronic illnesses. It emphasises the need to reinforce the concept of self-care and autonomy from early stages of care, and the importance of early planning of a healthy transition process, in accordance to the detected needs of the adolescents themselves. PMID- 26900103 TI - Longitudinal extensive transverse myelitis with cervical epidural haematoma following dengue virus infection. AB - BACKGROUND: Longitudinal extensive transverse myelitis associated with dengue infection is rare with no reported paediatric cases. METHODS: We report a 12-year old girl who presented with flaccid quadriplegia 8 days after onset of acute dengue fever. MRI spine showed T2 hyperintensity associated with epidural hematoma at C3-C6 level of the spinal cord. Transcranial magnetic brain stimulation revealed absent motor evoked potentials bilaterally. We also summarise and compare the reported cases of transverse myelitis associated with dengue infection. RESULTS: Immunomodulatory treatment was given which included pulse methylprednisolone, intravenous immunoglobulin and plasmapharesis. Six months post-admission, there was a good (near-complete) clinical recovery with the repeat MRI showing mild residual hyperintensity at C4 level and complete resolution of epidural haematoma. CONCLUSION: This is the first reported paediatric case of longitudinal extensive transverse myelitis following dengue infection. It is also the first to illustrate that in patients with concomitant epidural haematoma a good outcome is possible despite not having surgical decompression. Clinicians should be aware of parainfectious dengue-related longitudinal extensive transverse myelitis in children and consider prompt immunomodulatory treatment. PMID- 26900105 TI - Centrifugal photovoltaic and photogalvanic effects driven by structured light. AB - Much efforts are devoted to material structuring in a quest to enhance the photovoltaic effect. We show that structuring light in a way it transfers orbital angular momentum to semiconductor-based rings results in a steady charge accumulation at the outer boundaries that can be utilized for the generation of an open circuit voltage or a photogalvanic (bulk photovoltaic) type current. This effect which stems both from structuring light and matter confinement potentials, can be magnified even at fixed moderate intensities, by increasing the orbital angular momentum of light which strengthens the effective centrifugal potential that repels the charge outwards. Based on a full numerical time propagation of the carriers wave functions in the presence of light pulses we demonstrate how the charge buildup leads to a useable voltage or directed photocurrent whose amplitudes and directions are controllable by the light pulse parameters. PMID- 26900106 TI - Dissipation of disturbances seen in the knee joint kinematics of children with cerebral palsy. AB - PURPOSE: Children with cerebral palsy (CP) often use a crouch gait pattern that has disturbances in the knee joint kinematics. Although the length and rate of lengthening of the hamstring musculature have been speculated to be the reason that these disturbances are not adequately dissipated, this relationship has not been adequately explored. The purpose of this exploratory investigation was to use simulations of a musculoskeletal model and Floquet analysis to evaluate how the performance of hamstrings musculature during gait may be related to the knee joint instabilities seen in children with CP. METHODS: Children with CP and typically developing (TD) children walked on a treadmill as a motion capture system assessed the knee joint kinematics. Floquet analysis was used to quantify the rate that disturbances present at the knee joint were dissipated, and simulations of a musculoskeletal model were used to estimate the in vivo length and velocity of the hamstrings. Pearson correlation coefficients were calculated to determine if there was a relationship between the rate that the disturbances were dissipated and the performance of the hamstring musculature. RESULTS: The children with CP had hamstrings that lengthened more slowly than TD children, and required more strides to dissipate disturbances in the knee joint kinematics. There was negative correlation between the rate that the hamstrings lengthened and the rate that the knee joint disturbances were dissipated. CONCLUSIONS: Our results suggest that the ability of children with CP to dissipate the knee joint disturbances may be related to the inability to properly control the hamstring musculature. PMID- 26900104 TI - Autoantibodies against homocysteinylated protein in a mouse model of folate deficiency-induced neural tube defects. AB - BACKGROUND: Periconceptional supplementation with folic acid results in a significant reduction in the incidence of neural tube defects (NTDs). Nonetheless, NTDs remain a leading cause of perinatal morbidity and mortality worldwide, and the mechanism(s) by which folate exerts its protective effects are unknown. Homocysteine is an amino acid that accumulates under conditions of folate-deficiency, and is suggested as a risk factor for NTDs. One proposed mechanism of homocysteine toxicity is its accumulation into proteins in a process termed homocysteinylation. METHODS & RESULTS: Herein, we used a folate-deficient diet in pregnant mice to demonstrate that there is: (i) a significant inverse correlation between maternal serum folate levels and serum homocysteine; (ii) a significant positive correlation between serum homocysteine levels and titers of autoantibodies against homocysteinylated protein; and (iii) a significant increase in congenital malformations and NTDs in mice deficient in serum folate. Furthermore, in mice administered the folate-deplete diet before conception, supplementation with folic acid during the gestational period completely rescued the embryos from congenital defects, and resulted in homocysteinylated protein titers at term that are comparable to that of mice administered a folate-replete diet throughout both the pre- and postconception period. These results demonstrate that a low-folate diet that induces NTDs also increases protein homocysteinylation and the subsequent generation of autoantibodies against homocysteinylated proteins. CONCLUSION: These data support the hypotheses that homocysteinylation results in neo-self antigen formation under conditions of maternal folate deficiency, and that this process is reversible with folic acid supplementation. PMID- 26900107 TI - A Tailor-Made Synthetic Polymer for Cell Encapsulation: Design Rationale, Synthesis, Chemical-Physics and Biological Characterizations. AB - This study presents a custom-made in situ gelling polymeric precursor for cell encapsulation. Composed of poly((2-hydroxyethyl)methacrylate-co-(3 aminopropyl)methacrylamide) (P(HEMA-co-APM) mother backbone and RGD-mimicking poly(amidoamine) (PAA) moiteis, the comb-like structured polymeric precursor is tailored to gather the advantages of the two families of synthetic polymers, i.e., the good mechanical integrity of PHEMA-based polymers and the biocompatibility and biodegradability of PAAs. The role of P(HEMA-co-APM) in the regulation of the chemico-physical properties of P(HEMA-co-APM)/PAA hydrogels is thoroughly investigated. On the basis of obtained results, namely the capability of maintaining vital NIH3T3 cell line in vitro for 2 d in a 3D cell culture, the in vivo biocompatibility in murine model for 16 d, and the ability of finely tuning mechanical properties and degradation kinetics, it can be assessed that P(HEMA-co-APM)/PAAs offer a cost-effective valid alternative to the so far studied natural polymer-based systems for cell encapsulation. PMID- 26900108 TI - Ginger Essential Oil Ameliorates Hepatic Injury and Lipid Accumulation in High Fat Diet-Induced Nonalcoholic Fatty Liver Disease. AB - The objective of this study was to investigate the hepatoprotective efficacy and mechanism of action of ginger essential oil (GEO) against the development of nonalcoholic fatty liver disease (NAFLD). Mice were maintained on either a control diet or high-fat diet (HFD) supplemented with GEO (12.5, 62.5, and 125 mg/kg) or citral (2.5 and 25 mg/kg) for 12 weeks. We demonstrated that GEO and its major component (citral) lowered HFD-induced obesity in a dose-dependent manner, accompanied by anti-hyperlipidemic effects by reducing serum free fatty acid, triglyceride, and total cholesterol levels. Moreover, liver histological results showed that administration of 62.5 and 125 mg/kg GEO and 25 mg/kg citral significantly reduced hepatic lipid accumulation. Further assessment by Western blotting and investigation of the lipid metabolism revealed that hepatic protein expression of sterol regulatory element-binding protein-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), and cytochrome P450 2E1 (CYP2E1) were down-regulated by GEO and citral, indicating that GEO and citral suppressed HFD-stimulated lipid biosynthesis and oxidative stress. Furthermore, GEO and citral effectively enhanced the antioxidant capacities and reduced inflammatory response in mouse liver, which exerted protective effects against steatohepatitis. Collectively, GEO and citral exhibited potent hepatoprotective effects against NAFLD induced by HFD in obese mice. Thus, GEO might be an effective dietary supplement to ameliorate NAFLD-related metabolic diseases, and citral could play a vital role in its management. PMID- 26900109 TI - Hypertension in Canada and the Global Context. The Wine Is Vintage and the Glass Is Two-Thirds Full, but Is the Bottle Empty? PMID- 26900110 TI - The Ethics of Medical Volunteerism. AB - Responding to disparities in health, thousands of health care providers volunteer annually for short-term medical service trips (MSTs) to serve communities in need as a result of environmental, geographic, historical, or sociopolitical factors. Although well intentioned, short-term MSTs have the potential to benefit and harm those involved, including participants and communities being served. The contexts, resource and time limitations, and language and cultural barriers present ethical challenges. There have been increasing requests for standardized global guidelines, transparency, and open review of MSTs and their outcomes. Principles of mission, partnership, preparation, reflection, support, sustainability, and evaluation inform and equip those engaging in medical volunteerism. PMID- 26900111 TI - Immunizations. AB - Vaccinations are a cornerstone of the pretravel consultation. The pretravel provider should assess a traveler's past medical history, planned itinerary, activities, mode of travel, and duration of stay and make appropriate vaccine recommendations. Given that domestic vaccine-preventable illnesses are more common in international travelers than are exotic or low-income nation-associated vaccine-preventable illnesses, clinicians should first ensure that travelers are current regarding routine immunizations. Additional immunizations may be indicated in some travelers. Familiarity with geographic distribution and seasonality of infectious diseases is essential. Clinicians should be cognizant of which vaccines are live, as there exist contraindications for live vaccines. PMID- 26900112 TI - Travel Medical Kit. AB - "The traveler's medical kit is an essential tool for both the novice and expert traveler. It is designed to treat travel-related illness and injury and to ensure preexisting medical conditions are managed appropriately. Travelers are at increased risk for common gastrointestinal issues during travel. Respiratory illnesses make up approximately 8% of the ailments present in returned international travelers. Approximately 12% of travelers experience a travel related skin condition. First aid treatment for minor injuries is essential to all travel medical kits. The complexity ranges from a small, simple case for the urban traveler to a larger, extensive case for wilderness travel." PMID- 26900113 TI - Care for the Health Care Provider. AB - Pretravel care for the health care provider begins with an inventory, including the destination, length of stay, logistical arrangements, type of lodging, food and water supply, team members, personal medical needs, and the needs of the community to be treated. This inventory should be created and processed well in advance of the planned medical excursion. The key thing to remember in one's planning is to be a health care provider during one's global health care travel and not to become a patient oneself. This article will help demonstrate the medical requirements and recommendations for such planning. PMID- 26900114 TI - Malaria in the Traveler: How to Manage Before Departure and Evaluate Upon Return. AB - Malaria is the clinical syndrome when a patient experiences symptoms in response to infection with one of several strains of the Plasmodium parasite. This article is intended for health care providers to become familiar with some of the basics of care of patients who are travelling to or returning from an area with ongoing malaria transmission. The specific focus is on patients from nonendemic areas who plan on travel for a finite period to an area where malaria is endemic. PMID- 26900115 TI - Personal Protection Measures Against Mosquitoes, Ticks, and Other Arthropods. AB - Arthropod-associated diseases are a major cause of morbidity among travelers. Obtaining a detailed travel itinerary and understanding traveler-specific and destination-specific risk factors can help mitigate the risk of vector-borne diseases. DEET, picaridin, PMD, and IR3535 are insect repellents that offer sufficient protection against arthropod bites. IR3535 does not provide adequate protection against Anopheles mosquitoes, and should be avoided in malaria-endemic regions. General protective measures, such as bite avoidance, protective clothing, insecticide-treated bed nets, and insecticide-treated clothing, should be recommended, especially in malaria-endemic areas. Spatial repellents may prevent nuisance biting, but have not been shown to prevent against vector-borne disease. PMID- 26900116 TI - Traveler's Diarrhea. AB - Traveler's diarrhea (TD) is the most common travel-related illness, and it can have a significant impact on the traveler. Pretravel consultation provides an excellent opportunity for the clinician to counsel the traveler and discuss strategies such as food and water hygiene, vaccinations, and medications for prophylaxis or self-treatment that may decrease the incidence and impact of TD. Postinfectious sequelae, such as postinfectious irritable bowel syndrome, reactive arthritis, and Guillain-Barre syndrome, may develop weeks or months after return. PMID- 26900118 TI - Wilderness Medicine. AB - Wilderness medicine encompasses prevention and treatment of illness and injury, education and training, emergency medical services, and search and rescue in the wilderness. Although traumatic injuries, including minor injuries, outnumber medical illness as the cause of morbidity in the wilderness, basic understanding of the prevention and management of injury and illness, including recognition, identification, treatment, initial management, and stabilization, is essential, in addition to the ability to facilitate evacuation of affected patients. An important theme throughout wilderness medicine is planning and preparation for the best- and worst-case scenarios, and being ready for the unexpected. PMID- 26900117 TI - Road Traffic and Other Unintentional Injuries Among Travelers to Developing Countries. AB - Injuries result in nearly 6 million deaths and incur 52 million disability adjusted life-years annually, making up 15% of the global disease burden. More than 90% of this burden occurs in low- and middle-income countries. Given this burden, it is not unexpected that injuries are the leading cause of death among travelers to low- and middle-income countries, namely, from road traffic crashes and drowning. Therefore, pretravel advice regarding foreseeable dangers and how to avoid them may significantly mitigate injury risk, such as wearing seatbelts, helmets, and personal flotation devices when appropriate; responsibly consuming alcohol; and closely supervising children. PMID- 26900119 TI - High-Altitude Medicine. AB - Individuals may seek the advice of medical providers when considering travel to high altitude. This article provides a basic framework for counseling and evaluating such patients. After defining "high altitude" and describing the key environmental features at higher elevations, the physiologic changes that occur at high altitude and how these changes are experienced by the traveler are discussed. Clinical features and strategies for prevention and treatment of the main forms of acute altitude illness are outlined, and frameworks for approaching the common clinical scenarios that may be encountered regarding high-altitude travelers are provided. PMID- 26900120 TI - Adventure and Extreme Sports. AB - Adventure and extreme sports often involve unpredictable and inhospitable environments, high velocities, and stunts. These activities vary widely and include sports like BASE jumping, snowboarding, kayaking, and surfing. Increasing interest and participation in adventure and extreme sports warrants understanding by clinicians to facilitate prevention, identification, and treatment of injuries unique to each sport. This article covers alpine skiing and snowboarding, skateboarding, surfing, bungee jumping, BASE jumping, and whitewater sports with emphasis on epidemiology, demographics, general injury mechanisms, specific injuries, chronic injuries, fatality data, and prevention. Overall, most injuries are related to overuse, trauma, and environmental or microbial exposure. PMID- 26900121 TI - Illness in the Returned International Traveler. AB - Familiarity with the distribution, mode of transmission, and risk factors for acquisition of illnesses commonly transmitted to travelers to low-income nations can help guide clinicians in their work-up of an ill returned traveler. The 3 most common categories of illness in returned international travelers are gastrointestinal illness, fever, and dermatoses. Diarrhea is the most common illness reported in returned international travelers. Fever is a marker of a potentially significant illness; work-up of the ill febrile returned traveler should be conducted promptly. PMID- 26900122 TI - Travel and Adventure Medicine Resources. AB - Given the ever-changing nature of travel medicine, practitioners who provide pretravel and posttravel care are obligatorily students for the duration of their professional careers. A large variety of resources are available for medical practitioners. Providers should join at least one travel or tropical medicine professional association, attend its annual meeting, and read its journal. The largest general travel medicine association is the International Society of Travel Medicine. PMID- 26900123 TI - Travel and Adventure Medicine. PMID- 26900124 TI - Travel and Adventure Medicine. PMID- 26900127 TI - Rationalizing ethnopharmacological uses of Alternanthera sessilis: A folk medicinal plant of Pakistan to manage diarrhea, asthma and hypertension. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Tribal herbal practitioners of Pakistan use Alternanthera sessilis (Amaranthaceae) to treat diarrhea, asthma and hypertension. OBJECTIVE: The current study was conducted to provide mechanistic basis for anti-spasmodic, anti- asthmatic and anti-hypertensive use of Alternanthera sessilis. MATERIALS AND METHODS: The crude ethanolic extract of Alternanthera sessilis (As.Cr) and its fractions were tested in- vitro on isolated rabbit tissue preparations (i.e., jejunum, trachea, and aorta) and in vivo in ketamin-diazepam anaesthetized normotensive rats.The responses were recorded using isotonic and isometric transducers coupled with Power Lab data acquisition system. RESULTS: On isolated rabbit jejunum preparations, As.Cr exerted concentration-dependent (0.01-1.0mg/ml) spasmolytic effect and caused relaxation of K(+)(80mM)-induced spastic contractions. Furthermore, there was non parallel shift in Ca(++)concentration response curves (CRCs) towards right at tissue bath concentrations of 0.1 and 0.3mg/ml. On isolated rabbit trachea, it relaxed carbachol (1MUM)- and K(+()80mM)-induced contractions at respective tissue bath concentrations of 5.0 and 1.0mg/ml. On isolated rabbit aorta, it also demonstrated relaxant effect on phenylephrine (1MUM)- and K(+()80mM)-induced contractions at tissue bath concentrations of 5.0 and 3.0mg/ml respectively. These findings were found to be comparable with verapamil, a reference Ca(++)channel blocker (CCB). The solvent-solvents fractionation revealed domination of spasmolytic effects in dichloromethane fraction as compared to aqueous fraction. Intravenous administration of As.Cr decreased mean arterial blood pressure, systolic blood pressure and diastolic blood pressure of ketamine diazepam anaesthetized normotensive albino rats dose-dependently, at dose range of 1-10mg/kg. CONCLUSION: Our results reflected presence of Ca(++) channel blocking (CCB) activity in As.Cr, thus rationalizing medicinal use of Alternanthera sessilis in diarrhea, asthma and hypertension. PMID- 26900125 TI - Detection and delineation of oral cancer with a PARP1 targeted optical imaging agent. AB - Earlier and more accurate detection of oral squamous cell carcinoma (OSCC) is essential to improve the prognosis of patients and to reduce the morbidity of surgical therapy. Here, we demonstrate that the nuclear enzyme Poly(ADP ribose)Polymerase 1 (PARP1) is a promising target for optical imaging of OSCC with the fluorescent dye PARPi-FL. In patient-derived OSCC specimens, PARP1 expression was increased 7.8 +/- 2.6-fold when compared to normal tissue. Intravenous injection of PARPi-FL allowed for high contrast in vivo imaging of human OSCC models in mice with a surgical fluorescence stereoscope and high resolution imaging systems. The emitted signal was specific for PARP1 expression and, most importantly, PARPi-FL can be used as a topical imaging agent, spatially resolving the orthotopic tongue tumors in vivo. Collectively, our results suggest that PARP1 imaging with PARPi-FL can enhance the detection of oral cancer, serve as a screening tool and help to guide surgical resections. PMID- 26900128 TI - Antipyretic, analgesic and anti-inflammatory effects of Kickxia ramosissima. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Branched cancerwort, Kickxia ramosissima (Wall.) Janchen (Scrophulariaceae) is traditionally used for the treatment of inflammatory disorders such as rheumatism, diabetes, jaundice and for activation of immune system. Local communities also used this plant for the treatment of spleen enlargement, as febrifuge and in dysmenorrhea. In this investigation antipyretic, analgesic and anti-inflammatory effects of K. ramosissima have been evaluated. METHODS: Dried powder of the whole plant of K. ramosissima was extracted with methanol (KRM) and partitioned with solvents to obtain the n hexane (KRH), chloroform (KRC), ethyl acetate (KRE), n-butanol (KRB) and the residual aqueous (KRA) fraction. KRM and the derived fractions were analyzed for the phytochemical constituents, yeast induced pyrexia, analgesic and anti inflammatory activities by using carrageenan and Freunds' complete adjuvant induced paw edema model in rat. On account of appreciable effects of KRM in the aforesaid models, KRM was subjected to the carrageenan induced air pouch model in rat. The exudate of air pouch was analyzed for the count of neutrophils, monocytes, lymphocytes and WBCs and for the estimation of tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), nitric oxide (NO) and prostaglandin (PGE2). RESULTS: Phytochemical investigation of KRM indicated the existence of tannins, flavonoids, alkaloids, coumarins, cardiac glycosides, saponins, terpenoids and phlobatannins. Maximum concentration of total phenolic was determined in KRB followed by KRM while reverse was true for total flavonoids contents. KRM (200mg/kg) distinctly decreased the rectal temperature in yeast induced pyrexia comparable to standard, paracetamol. Pain sensation was effectively inhibited at 200mg/kg p.o. of KRM and KRB as manifested by a decrease (P<0.001) in count of writhing induced with acetic acid and increase of latency time in hot plate. Anti-inflammatory effects of KRM were evident and edema formation induced with carrageenan and Freunds' complete adjuvant-induced paw edema in rat was significantly (P<0.001) inhibited. Count of neutrophils, monocytes, lymphocytes, and WBCs along with inflammatory mediators; IL-6, NO, TNF alpha and PGE2 was significantly (P<0.001) decreased in subcutaneous air pouch exudate with KRM. HPLC analysis of KRM indicated the presence of gallic acid, caffeic acid, rutin, catechin and myricetin. CONCLUSION: The results suggested the anti-inflammatory effects of KRM in inflammation related disorders, might be attributed by the presence of active phytoconstituents; flavonoids, saponins and terpenoids. PMID- 26900126 TI - Opuntia dillenii cladode: Opuntiol and opuntioside attenuated cytokines and eicosanoids mediated inflammation. AB - ETHANOPHARMACOLOGICAL RELEVANCE: Opuntia dillenii Haw (Nagphana) traditionally used against inflammation. The present study addressed the anti-inflammatory activity of O. dillenii derived methanol extract, fractions and pure compounds and their underlying mechanism of action. MATERIALS AND METHODS: O. dillenii cladode methanol extract was subjected to vacuum liquid chromatography (VLC) furnishing two main fractions viz (T-1 and -2) leading to isolation of opuntiol (aglycone) and opuntioside (O-glucoside), respectively. Anti-inflammatory activity of extract, fractions, pure compounds and reference drugs were evaluated using: (1) arachidonic acid (AA) and 12-O-tetradecanoyl-phorbol-13-acetate (TPA) induced ear edema accompanied by histological studies of mice ear sections and phospholipase A2 (PLA2)-induced mice paw edema. (2) Carrageenan and glycogen induced peritonitis in rodents. In parallel levels of leukotriene B4 (LTB4) and reactive oxygen species (ROS) were also determined via HPLC and fluoroemetrically using 2', 7'-dichlorodihydrofluorescein diacetate (DCFH-DA) dye, respectively. Additionally, levels of prostaglandin E2 (PGE2), tumor necrosis factor (TNF alpha), interleukins IL-1beta and -6 were measured by ELISA assay. RESULTS: O. dillenii methanol extract, fractions and pure compounds reduced AA and TPA induced ear punch weight in a dose dependent fashion. The corresponding IC50 values obtained also suppressed inflammatory features observed histologically. Furthermore, paw edema and peritonitis were also attenuated. Similar to indomethacin and diclofenac sodium, opuntioside reduced PGE2 levels of inflamed ear which was comparatively 1.3* better than opuntiol. However, opuntiol was more potent in reducing LTB4 levels in rat neutrophils with an IC50 value of 19+/ 3.3MUMU, while opuntioside was ineffective. Opuntiol also effectively suppressed ROS (37%) and cytokine levels (TNF-alpha, IL-1beta and -6) by ~50% and comparable to dexamethasone. CONCLUSIONS: O. dillenii cladodes possess anti-inflammatory properties via inhibition of arachidonic acid metabolites and cytokines. Opuntiol (aglycone) emerged as a dual inhibitor of cyclooxygenase (COX) and lipooxygenase (LOX) pathways. It also suppressed ROS and cytokine levels. However, opuntioside manifested its selectivity towards COX (PGE2) pathway without affecting LTB4 levels. The present report describing the anti-inflammatory activity of opuntiol and opuntioside for the first time thereby, supporting and justifying the traditional use of O. dillenii against inflammation and may serve as lead compound in designing of new anti-inflammatory agents. PMID- 26900129 TI - Ethnomedical and ethnobotanical investigations on the response capacities of Guinean traditional health practioners in the management of outbreaks of infectious diseases: The case of the Ebola virus epidemic. AB - ETHNOPHARMACOLOGICAL RELEVANCE: The recent outbreak of Ebola virus infections has mostly remained confined to the West African countries Guinea-Conakry, Sierra Leone and Liberia. Due to intense national and international mobilizations, a significant reduction in Ebola virus transmission has been recorded. While international efforts focus on new vaccines, medicines and diagnostics, no coherent national or international approach exists to integrate the potential of the traditional health practitioners (THPs) in the management of infectious diseases epidemics. Nevertheless, the first contact of most of the Ebola infected patients is with the THPs since the symptoms are similar to those of common traditionally treated diseases or symptoms such as malaria, hemorrhagic syndrome, typhoid or other gastrointestinal diseases, fever and vomiting. MATERIALS AND METHODS: In an ethnomedical survey conducted in the 4 main Guinean regions contacts were established with a total of 113 THPs. The socio-demographic characteristics, the professional status and the traditional perception of Ebola Virus Disease (EVD) were recorded. RESULTS: The traditional treatment of the main symptoms was based on 47 vegetal recipes which were focused on the treatment of diarrhea (22 recipes), fever (22 recipes), vomiting (2 recipes), external antiseptic (2 recipes), hemorrhagic syndrome (2 recipes), convulsion and dysentery (one recipe each). An ethnobotanical survey led to the collection of 54 plant species from which 44 identified belonging to 26 families. The most represented families were Euphorbiaceae, Caesalpiniaceae and Rubiaceae. Literature data on the twelve most cited plant species tends to corroborate their traditional use and to highlight their pharmacological potential. CONCLUSIONS: It is worth to document all available knowledge on the traditional management of EVD like symptoms in order to evaluate systematically the anti-Ebola potential of Guinean plant species. PMID- 26900130 TI - Detecting Spatial Chromatin Organization by Chromosome Conformation Capture II: Genome-Wide Profiling by Hi-C. AB - The chromosome conformation capture (3C) method has been invaluable in studying chromatin interactions in a population of cells at a resolution surpassing that of light microscopy, for example in the detection of functional contacts between enhancers and promoters. Recent developments in sequencing-based chromosomal contact mapping (Hi-C, 5C and 4C-Seq) have allowed researchers to interrogate pairwise chromatin interactions on a wider scale, shedding light on the three dimensional organization of chromosomes. These methods present significant technical and bioinformatic challenges to consider at the start of the project. Here, we describe two alternative methods for Hi-C, depending on the size of the genome, and discuss the major computational approaches to convert the raw sequencing data into meaningful models of how genomes are organized. PMID- 26900133 TI - Targeting Mitochondrial Biogenesis and Mitochondrial Substrate Utilization to Treat Obesity and Insulin Resistance, Respectively - Two Data-Driven Hypotheses. AB - INTRODUCTION: The mitochondrion plays a critical role in cellular energy metabolism. For this reason it is considered as a plausible target for the treatment of metabolic diseases such as obesity and type-2 diabetes. Although several mitochondrial molecular targets have been suggested and investigated, currently there are no marketed drugs that target the mitochondrion to treat metabolic diseases. Through an investigation of current drugs and investigational compounds, two hypotheses have emerged: 1) inhibition of mitochondrial substrate utilization is associated with increased insulinstimulated glucose uptake; 2) stimulation of mitochondrial biogenesis is related to increased energy expenditure and potentially weight loss. The mode-of-action of both mechanistic hypotheses is currently unknown and potentially controversial since they contradict other experimental findings. However, the fact that both processes are stimulated by different types of compounds with different sites of action supports their potential existence. CONCLUSION: This review summarizes the data that support these two hypotheses; with the hope that this will stimulate further research and intensify the development of future drugs for the treatment of obesity and type-2 diabetes. PMID- 26900131 TI - Associations between metabolic disorders and risk of cancer in Danish men and women--a nationwide cohort study. AB - BACKGROUND: The prevalence of metabolic disorders is increasing and has been suggested to increase cancer risk, but the relation between metabolic disorders and risk of cancer is unclear, especially in young adults. We investigated the associations between diabetes, hypertension, and hypercholesterolemia on risk of all-site as well as site-specific cancers. METHODS: We consecutively included men and women from nationwide Danish registries 1996-2011, if age 20-89 and without cancer prior to date of entry. We followed them throughout 2012. Metabolic disorders were defined using discharge diagnosis codes and claimed prescriptions. We used time-dependent sex-stratified Poisson regression models adjusted for age and calendar year to assess associations between metabolic disorders, and risk of all-site and site-specific cancer (no metabolic disorders as reference). RESULTS: Over a mean follow-up of 12.6 (+/- 5.7 standard deviations [SD]) years, 4,826,142 individuals (50.2% women) with a mean age of 41.4 (+/- 18.9 SD) years had 423,942 incident cancers. Incidence rate ratios (IRRs) of all-site cancer in patients with diabetes or hypertension were highest immediately following diagnosis of metabolic disorder. In women, cancer risk associated with diabetes continued to decline albeit remained significant (IRRs of 1.18-1.22 in years 1-8 following diagnosis). For diabetes in men, and hypertension, IRRs stabilized and remained significantly increased after about one year with IRRs of 1.10-1.13 in men for diabetes, and 1.07-1.14 for hypertension in both sexes. Conversely, no association was observed between hypercholesterolemia (treatment with statins) and cancer risk. The association between hypertension and cancer risk was strongest in young adults aged 20-34 and decreased with advancing age. CONCLUSIONS: Diabetes and hypertension were associated with increased risk of all site cancer. PMID- 26900132 TI - Impact of interventions to reduce Alzheimer's disease pathology on the prevalence of dementia in the oldest-old. AB - INTRODUCTION: The number of persons aged >90 years will grow significantly in coming decades. This group has the highest rates of dementia, most commonly Alzheimer's disease (AD). METHODS: Using The 90+ Study, we developed a statistical model for dementia risk based on brain pathologies. Intervention scenarios which reduce or eliminate AD pathology were considered, and the numbers of dementia cases among the U.S. oldest-old that could be prevented were estimated. RESULTS: The U.S. dementia prevalence among the oldest-old will increase from 1.35 million in 2015 to 4.72 million in 2050. If interventions eliminate AD pathology, dementia prevalence would be reduced by approximately 50%, averting nearly 2.4 million cases in 2050. However, large numbers of dementia cases would still remain. DISCUSSION: Reducing AD pathology would significantly decrease the public health burden of dementia. However, other interventions are needed to address the burden associated with other dementing pathologies prevalent in the oldest-old. PMID- 26900134 TI - Mitochondrial Uncoupling and the Regulation of Glucose Homeostasis. AB - INTRODUCTION: Mitochondrial uncoupling is a physiological process that has direct and indirect consequences on glucose homeostasis. Non-shivering thermogenesis in brown adipose tissue, which is the most well-recognized biological process related to the physiological uncoupling of mitochondria, is caused by uncoupling protein-1 (UCP1), which mediates a regulated permeabilization of the mitochondrial inner membrane to protons. CONCLUSION: The uncoupled brown fat mitochondria are specialized to produce heat by oxidizing large amounts of substrates, making brown fat a sink that can actively drain glucose from circulation. This has been confirmed in human studies in which active brown fat was detected by glucose-derivative-based positron emission tomography scans. Thus, UCP1-mediated activation of brown fat appears to be a likely mechanism through which hyperglycemia could be ameliorated. In other tissues, mitochondria are reported to be mildly uncoupled by the UCP1-like proteins, UCP2 and UCP3. The primary role of these other UCPs does not appear to be the oxidation of a metabolic substrate (e.g., glucose) for heat production; instead, they participate in other processes, such as regulating the production of reactive oxygen species and transporting certain metabolites across the mitochondrial membrane. UCP2 activity influences glucose homeostasis by fine tuning intracellular events related to the cellular energy status, thereby controlling insulin secretion, food intake behavior and adiponectin secretion in pancreatic . cells, brain and white adipose tissue, respectively. UCP3 appears to be more specifically involved in promoting fatty acid oxidation in muscle, and is thus likely to influence glucose metabolism indirectly. Several genetic association studies have related polymorphisms in the genes encoding UCPs with obesity and/or type 2 diabetes phenotypes. In this review, we will focus on what is known about the specific role of mitochondrial uncoupling in glucose metabolism, and its implications in diabetes. PMID- 26900135 TI - Autophagy and Mitochondria in Obesity and Type 2 Diabetes. AB - INTRODUCTION: Obesity and type 2 diabetes are growing health problems worldwide. The three principal diabetogenic factors are adiposity, insulin resistance in skeletal muscle, and decreased insulin production by pancreatic beta cells. During recent years, macroautophagy (hereafter autophagy) - sequestration and lysosomal degradation of cellular components - has emerged as an important player in these processes, playing a protective role against development of insulin resistance and diabetes. Of particular importance is the removal of dysfunctional mitochondria via mitophagy, a form of macroautophagy selective for mitochondria. Both muscle insulin resistance and beta-cell dysfunction largely depend on metabolic overload of mitochondria, which results in incomplete beta-oxidation, oxidative stress, accumulation of toxic lipid intermediates, and mitochondrial damage. Mitophagy eliminates this vicious cycle of oxidative stress and mitochondrial damage, and thus counteracts pathogenic processes. Autophagy also mediates exercise-induced increases in muscle glucose uptake and protects beta cells against ER stress in diabetogenic conditions. On the other hand, adipose tissue autophagy promotes adipocyte differentiation, possibly through its role in mitochondrial clearance. Being involved in many aspects, autophagy appears to be an attractive target for therapeutic interventions against obesity and diabetes. CONCLUSION: Here we explore the connections of autophagy with mitochondria in obesity and type 2 diabetes, and discuss its roles in diabetic complications. Understanding how autophagy protects against diabetes could help design new strategies against this growing epidemic. PMID- 26900136 TI - Mitochondrial Post-translational Modifications and Metabolic Control: Sirtuins and Beyond. AB - INTRODUCTION: In order to maintain metabolic homeostasis, organisms adjust the capacity and efficiency of ATP generation to changes in energetic demand and supply. While the transcriptional control of mitochondrial biogenesis allows to adapt mitochondrial respiratory capacity with long-term requirements for differential energy demand (e.g.: exercise training), bioenergetic adaptation also needs to take place within shorter time frames in order to properly fine tune nutrient availability, energy production and demand, either in a circadian fashion or after a meal. These quick metabolic responses can be achieved through exquisite modulation of diverse post-translational modifications, which influence a variety of mitochondrial processes, including mitochondrial dynamics, fatty acid oxidation, lipogenesis and bioenergetic efficiency. CONCLUSION: In this review, we will specially focus on the role of mitochondrial sirtuin enzymes as modulators of mitochondrial ac(et)ylation and the possible interactions with other posttranslational modification events. PMID- 26900137 TI - The globus pallidus pars interna in goal-oriented and routine behaviors: Resolving a long-standing paradox. AB - BACKGROUND: There is an apparent contradiction between experimental data showing that the basal ganglia are involved in goal-oriented and routine behaviors and clinical observations. Lesion or disruption by deep brain stimulation of the globus pallidus interna has been used for various therapeutic purposes ranging from the improvement of dystonia to the treatment of Tourette's syndrome. None of these approaches has reported any severe impairment in goal-oriented or automatic movement. METHOD: To solve this conundrum, we trained 2 monkeys to perform a variant of a 2-armed bandit-task (with different reward contingencies). In the latter we alternated blocks of trials with choices between familiar rewarded targets that elicit routine behavior and blocks with novel pairs of targets that require an intentional learning process. RESULTS: Bilateral inactivation of the globus pallidus interna, by injection of muscimol, prevents animals from learning new contingencies while performance remains intact, although slower for the familiar stimuli. We replicate in silico these data by adding lateral competition and Hebbian learning in the cortical layer of the theoretical model of the cortex basal ganglia loop that provided the framework of our experimental approach. CONCLUSION: The basal ganglia play a critical role in the deliberative process that underlies learning but are not necessary for the expression of routine movements. Our approach predicts that after pallidotomy or during stimulation, patients should have difficulty with complex decision-making processes or learning new goal-oriented behaviors. (c) 2016 Movement Disorder Society. PMID- 26900138 TI - Healing process following laser cordectomy of early glottis carcinoma from endoscopic view. AB - BACKGROUND AND OBJECTIVE: Transoral laser surgery is useful for treating early glottic carcinoma. Wound areas after carbon dioxide (CO2 ) laser surgery are not covered by flaps, delaying healing. The healing process following laser cordectomy is not well understood. In this study, laryngoscopes were used to monitor the normal healing process after laser cordectomy and to determine if there was residual or recurrent disease. MATERIALS AND METHODS: This prospective case study included 36 patients who underwent CO2 laser surgery for early glottis carcinoma between January 2011 and June 2014 at a university tertiary referral center. Postoperative complications, oncologic results, and mucosal stabilization time were analyzed. Vocal fold stabilization was defined as an absence of gross changes during two consecutive follow-up examinations. RESULTS: The 3-year overall survival rate was 100% and the 3-year local control rate was 94%. Vocal cord stabilization was observed in 29 patients at a mean 88.1 days, with stabilization associated with the type of cordectomy (P < 0.05). During the wound healing process, two patients experienced local recurrences. One had a persistent white patch for over 4 months and the other presented with a new mass in a non operated area. Biopsies of both lesions showed recurrent disease. Postoperative complications included granulation in two patients and anterior commissure adhesion in one. CONCLUSION: CO2 laser microsurgery is an effective treatment for early glottis carcinoma. Close attention should be paid to delays in healing process after laser surgery. Interventions should be considered for patients with abnormal laryngoscopic appearance or overly prolonged healing. Lasers Surg. Med. 48:483-489, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26900139 TI - Postoperative wound infections after a proctectomy--Patient experiences. AB - Poor perineal wound healing and infections after proctectomy surgery cause a significant proportion of physical and psychological morbidities, such as pain, leakage, and abscesses. In the long run, some of these symptoms will lead to extended periods of hospitalization. These kinds of postoperative complications are also associated with delays in possible chemotherapy treatment. The aim of this study was to describe patient experiences of perineal wound infections following proctectomy due to rectal cancer, and the importance of the communication with and the self-care support from the nurse for these patients. Five women and five men (61-87 years, median age 71 years) were included and interviewed. A qualitative content analysis of the interviews was carried out and the following main categories emerged: "Managing postoperative complications," "Being independent," "Feeling safe," and "Accepting the situation." A perineal wound infection after a proctectomy is devastating for the individual patient. The limitations and changes to the patients' lives turn into new daily routines, which force them to find new ways to live and to accept the situation. For many of them, the infections remained for several months and, sometimes, for years. The ability to lead an independent life is drastically reduced, but through continuity in care it is possible to create a feeling of safety. Information, communication, and self-care support are all important and valuable factors for recovery. Specialized care containing an action plan is therefore needed in clinical practice to reduce the number of perineal wound infections postoperatively and should be initiated when the patient is discharged from the ward and continue until recovery. PMID- 26900140 TI - [The policy of systematic first line IVF in patients with severe deep endometriosis and pregnancy intention: A thin scientific support with severe collateral damages]. PMID- 26900141 TI - Association-Dissociation of Glycolate Oxidase with Catalase in Rice: A Potential Switch to Modulate Intracellular H2O2 Levels. AB - Rapid and dynamic change in hydrogen peroxide (H2O2) levels can serve as an important signal to regulate various biological processes in plants. The change is realized by tilting the balance between its production and scavenging rates, in which membrane-associated NADPH oxidases are known to play a crucial role. Functioning independently from NADPH oxidases, glycolate oxidase (GLO) was recently demonstrated as an alternative source for H2O2 production during both gene-for-gene and non-host resistance in plants. In this study, we show that GLO physically interacts with catalase (CAT) in rice leaves, and that the interaction can be deregulated by salicylic acid (SA). Furthermore, the GLO-mediated H2O2 accumulation is synergistically enhanced by SA. Based on the well-known mechanism of substrate channeling in enzyme complexes, SA-induced H2O2 accumulation likely results from SA-induced GLO-CAT dissociation. In the GLO-CAT complex, GLO mediated H2O2 production during photorespiration is very high, whereas the affinity of CAT for H2O2 (measured Km ~ 43 mM) is extraordinarily low. This unique combination can further potentiate the increase in H2O2 when GLO is dissociated from CAT. Taken together, we propose that the physical association dissociation of GLO and CAT, in response to environmental stress or stimuli, seems to serve as a specific mechanism to modulate H2O2 levels in rice. PMID- 26900142 TI - Less is more: "incision and curettage" as an optimal procedure for recurrent pilonidal disease. AB - AIM: Although pilonidal disease has been a well-known entity for more than a century, recurrence of pilonidal disease is still not rare. The optimal surgical approach to recurrent disease is under debate. In this study, we aimed to investigate the efficacy of "incision and curettage" procedure for recurrent pilonidal disease. MATERIAL AND METHODS: From May 2009 to May 2013, 42 patients (37 male/5 female) underwent surgical treatment for recurrent pilonidal disease. Incision and curettage of granulation tissue, hair and debris in the cavity were performed in all cases. Data collection included demographics, visual analogue scale (VAS) score, hospital stay, return to daily activities (lying, sitting down in comfort) and work, and complete wound healing time. RESULTS: Mean operating time was 16.6+/-4.7 (10-24) minutes. Mean pain score was 1.4+/-1.1 (0-5) with VAS. The mean duration of returning to daily activities such as comfortable lying down, sitting and returning to work were 1.6+/-0.8 (1-4) days, and 3.3+/-2.3 (1 15) days, and 10.2+/-5.4 (5-33) days, respectively. The mean wound healing time was 19.9+/-7.8 (7-52) days. During the three-year follow-up period, no recurrence was observed. DISCUSSION: "Incision and curettage" may be performed as first-line treatment for recurrent cases. It does not require surgical skill and can be easily applied in a short time. CONCLUSION: This simple surgical option, incision curettage provides short hospital stay and quick return to daily activities, in addition to patient comfort and satisfaction. KEY WORDS: Pilonidal sinus, Recurrence, Sacrococcygeal. PMID- 26900143 TI - Frequency and complications after operative fixation of clavicular fractures. AB - BACKGROUND: The purpose of this study was to analyze whether a recent trend in evidence supporting operative treatment of clavicular fractures is matched with an increase in operative fixation and complication rates in the United States. METHODS: The American Board of Orthopaedic Surgery database was reviewed for cases with Current Procedural Terminology (American Medical Association, Chicago, IL, USA) code 23515 (clavicle open reduction internal fixation [ORIF]) from 1999 to 2010. The procedure rate for each year and the number of procedures for each candidate performing clavicle ORIF were calculated to determine if a change had occurred in the frequency of ORIF for clavicular fractures. Complication and outcome data were also reviewed. RESULTS: In 2010 vs, 1999, there were statistically significant increases in the mean number of clavicle ORIF performed among all candidates (0.89 vs. 0.13; P < .0001) and in the mean number of clavicle ORIF per candidate performing clavicle ORIF (2.47 vs. 1.20, P < .0473). The difference in the percentage of part II candidates performing clavicle ORIF from the start to the end of the study (11% vs. 36%) was significant (P < .0001). There was a significant increase in the clavicle ORIF percentage of total cases (0.11% vs. 0.74%, P < .0001). The most common complication was hardware failure (4%). CONCLUSION: The rate of ORIF of clavicular fractures has increased in candidates taking part II of the American Board of Orthopaedic Surgery, with a low complication rate. The increase in operative fixation during this interval may have been influenced by literature suggesting improved outcomes in patients treated with operative stabilization of their clavicular fracture. PMID- 26900144 TI - Hemiglossectomy tongue reconstruction: Modeling of elevation, protrusion, and functional outcome using receiver operator characteristic curve. AB - BACKGROUND: The purpose of this study was to model >12 month speech and the oral phase of swallowing outcomes with the reconstructive metrics of tongue elevation and protrusion in patients reconstructed with the rectangle tongue template for a hemiglossectomy defect. METHODS: We conducted a study using 40 surviving patients (23 men, 17 women) treated between 2000 and 2012. Statistically significant correlations of elevation and protrusion with functional outcomes were modeled with receiver operator characteristic (ROC) curves to understand the performance and reliability of the rectangle tongue reconstruction. RESULTS: Tongue elevation (1.8-1.9 cm) reliably produces best outcomes in nutritional mode, range of liquids, and >=4/6 for range of solids. Greater tongue elevation (2.1-2.2 cm) reliably produces best outcomes for eating and speaking in public and understandability of speech. Tongue protrusion (0.8-1.0 cm) reliably produces best scores across all assessed outcomes except >=4/6 for range of solids and >=4/5 understandability of speech. CONCLUSION: ROC curves are useful for assessing reliability and relating reconstructive objectives to functional outcomes. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: 1066-1073, 2016. PMID- 26900145 TI - Preference weights for the spectrum of alcohol use in the U.S. Population. AB - BACKGROUND: Little is known about the cost-utility of population-based alcohol interventions. One barrier to research has been the lack of preference weights needed to calculate Quality Adjusted Life Years (QALYs). Preference weights can be estimated from measures of health-related quality of life (HRQOL). The objective of this study was to describe preference weights for the full spectrum of alcohol use. METHODS: This cross-sectional study included participants in both the National Health Interview Survey (NHIS; 1999-2002) and the Medical Expenditure Panel Survey (MEPS; 2000-2003). The AUDIT-C alcohol screen was derived from NHIS with scores categorized into 6 groups (0,1-3, 4-5, 6-7, 8-9, 10 12 points), ranging from nondrinking (0) to very severe unhealthy alcohol use (10 12). AUDIT-C scores were mapped to EQ-5D and SF-6D preference weights using the linked datasets and analyses adjusted for demographics. RESULTS: Among 17,440 participants, mean EQ-5D and SF-6D preference weights were 0.82 (95% CI 0.82 0.83) and 0.79 (95% CI 0.79-0.80), respectively. Adjusted EQ-5D preference weights for nondrinking (0.80; 95% CI 0.79-0.81) and moderate unhealthy drinking (0.85; 95% CI 0.84-0.86) were significantly different from low-risk drinking (0.83; 95% CI 0.83-0.84), but no other differences were significant. Results for the SF-6D were similar. CONCLUSIONS: This study provides EQ-5D and SF-6D preference weights for various alcohol use categories in a representative U.S. adult sample. However, neither measure suggested meaningful differences in HRQOL based on AUDIT-C categories. Self-reported alcohol consumption may not be associated with preference weights or generic instruments may not capture alcohol related differences in HRQOL. PMID- 26900146 TI - Response to Therapy With Teriparatide, Denosumab, or Both in Postmenopausal Women in the DATA (Denosumab and Teriparatide Administration) Study Randomized Controlled Trial. AB - Both antiresorptive and anabolic osteoporosis medications increase bone mineral density (BMD), but no single agent can restore normal bone strength in most osteoporotic patients. Moreover, the magnitude and consistency of the patient response to each individual agent vary depending on the anatomic site. In the DATA study, we reported that in postmenopausal osteoporotic women, 2 years of combined denosumab and teriparatide increase mean BMD at the hip and spine more than either drug alone. In the current analysis, we wished to determine if the individual rates of BMD response were also greater among women treated with both drugs. In DATA, 94 postmenopausal osteoporotic women (ages 51-91) were randomized to receive teriparatide (20 mcg subcutaneously daily), denosumab (60 mg subcutaneously every 6 mo), or both medications for 24 mo. The BMD of the total hip (TH), femoral neck (FN), and lumbar spine (LS) were assessed by dual-energy X ray absorptiometry. The 82 subjects who completed all 2-yr treatments were analyzed. Responders were defined as experiencing BMD increases of >3%. An "excellent response" was defined as an increase of >6%. Over 24 mo, TH BMD increased by >3% in 36%, 53%, and 92% of women in the teriparatide, denosumab, and combination groups, respectively, and by >6% in 11%, 17%, and 50% in the teriparatide, denosumab, and combination groups, respectively (p < 0.01 for all comparisons vs combination). FN response rates were similar to TH. In the LS, BMD increased by >3% in 85%, 93%, and 100% of women in the teriparatide, denosumab, and combination groups, respectively (p = nonsignificant for all comparisons) and by >6% in 63%, 78%, and 100% of women in the teriparatide, denosumab, and combination groups, respectively (combination vs teriparatide, p = 0.001; combination vs denosumab, p = 0.016). In summary, more women treated with 24 mo of combined denosumab and teriparatide achieved a significant response at the TH and FN than those treated with either drug alone. All women treated with both agents together experienced an excellent response at the LS. These results support the continued investigation of combined denosumab and teriparatide therapy in postmenopausal osteoporotic women utilizing clinical endpoints such as fracture reduction. PMID- 26900147 TI - Nighttime sleep duration, 24-hour sleep duration and risk of all-cause mortality among adults: a meta-analysis of prospective cohort studies. AB - A dose-response meta-analysis was conducted to summarize evidence from prospective cohort studies about the association of nighttime sleep duration and 24-hour sleep duration with risk of all-cause mortality among adults. Pertinent studies were identified by a search of Embase and PubMed databases to March 2015. A two-stage random-effects dose-response meta-analysis was used to combine study specific relative risks and 95% confidence intervals [RRs (95% CIs)]. Thirty-five articles were included. Compared with 7 hours/day, the RRs (95% CIs) of all-cause mortality were 1.07 (1.03-1.13), 1.04 (1.01-1.07), 1.01 (1.00-1.02), 1.07 (1.06 1.09), 1.21 (1.18-1.24), 1.37 (1.32-1.42) and 1.55 (1.47-1.63) for 4, 5, 6, 8, 9, 10 and 11 hours/day of nighttime sleep, respectively (146,830 death cases among 1,526,609 participants), and the risks were 1.09 (1.04-1.14), 1.05 (1.02-1.09), 1.02 (1.00-1.03), 1.08 (1.05-1.10), 1.27 (1.20-1.36), 1.53 (1.38-1.70) and 1.84 (1.59-2.13) for 4, 5, 6, 8, 9, 10 and 11 hours/day of 24-hour sleep, respectively (101,641 death cases among 903,727 participants). The above relationships were also found in subjects without cardiovascular diseases and cancer at baseline, and other covariates did not influence the relationships substantially. The results suggested that 7 hours/day of sleep duration should be recommended to prevent premature death among adults. PMID- 26900148 TI - Cystic Adverse Local Tissue Reactions in Asymptomatic Modular Metal-on-Metal Total Hips May Decrease Over Time. AB - BACKGROUND: The presence of pain as a harbinger of bearing-related problems has recently been challenged. Adverse local tissue reactions (ALTRs) have been noted on cross-sectional imaging even in asymptomatic patients. The purpose of this study was to determine the natural history of such lesions in asymptomatic patients. METHODS: Eighty-three asymptomatic patients with modular metal-on-metal total hip arthroplasties underwent metal ion reports and metal artifact reduction sequence magnetic resonance imaging (MARS MRI). MARS MRI images were reviewed and evaluated for the presence or absence of an ALTR lesion by a musculoskeletal radiologist and the senior author. We defined an ALTR lesion as abnormal fluid collections, solid or semisolid pseudotumors, or muscle or bone damage and was classified according to the MRI Classification System of Hart et al. In addition, serum cobalt and chromium levels were measured and analyzed at the time of MRI. RESULTS: Twenty-six of 83 (31%) asymptomatic patients had cystic lesions identified. All patients with positive MRIs were contacted to have repeat studies a year later. Nineteen of 26 were available for follow-up. Three patients who became symptomatic were revised. Most ALTRs in asymptomatic patients with modular metal-on-metal total hip arthroplasties that underwent repeat MARS MRI decreased in size (15 of 19 [79%]); 3 lesions increased, whereas 1 remained the same. All patients in the series had Co and Cr ion levels below the threshold of 7 ppb. CONCLUSION: Although most cystic lesions decreased in size, vigilance is still required as 3 patients became symptomatic requiring revision. PMID- 26900149 TI - Acetaminophen induces accumulation of functional rat CYP3A via polyubiquitination dysfunction. AB - Acetaminophen (APAP) is extensively used as an analgesic and antipyretic drug. APAP is partly metabolized to N-acetyl-p-benzoquinone imine, a reactive metabolite, by cytochrome P450 (CYP) 1A2, 2E1 and 3A4. Some reports have indicated that CYP3A protein production and its metabolic activity are induced by APAP in rats in vivo. The CYP3A subfamily is believed to be transcriptionally regulated by chemical compounds. However, the mechanism underlying these responses is not completely understood. To clarify these mechanisms, we assessed the effects of APAP on CYP3A1/23 protein levels according to mRNA synthesis and protein degradation in rat hepatocyte spheroids, a model of liver tissue, in vivo. APAP induced CYP3A1/23 protein levels and metabolic activity. However, no change in CYP3A1/23 mRNA levels was observed. Moreover, APAP prolonged the half life of CYP3A1/23 protein. CYP3A is known to be degraded via the ubiquitin proteasome system. APAP significantly was found to decrease levels of polyubiquitinated CYP3A1/23 and glycoprotein 78, an E3 ligase of CYP3A1/23. These findings demonstrate that APAP induces accumulation of functional CYP3A protein via inhibition of protein degradation. Our findings may lead to the determination of novel drug-drug interactions with APAP. PMID- 26900150 TI - Sustained Endocannabinoid Signaling Compromises Decidual Function and Promotes Inflammation-induced Preterm Birth. AB - Recent studies provide evidence that premature maternal decidual senescence resulting from heightened mTORC1 signaling is a cause of preterm birth (PTB). We show here that mice devoid of fatty acid amide hydrolase (FAAH) with elevated levels ofN-arachidonyl ethanolamide (anandamide), a major endocannabinoid lipid mediator, were more susceptible to PTB upon lipopolysaccharide (LPS) challenge. Anandamide is degraded by FAAH and primarily works by activating two G-protein coupled receptors CB1 and CB2, encoded by Cnr1 and Cnr2, respectively. We found thatFaah(-/-)decidual cells progressively underwent premature senescence as marked by increased senescence-associated beta-galactosidase (SA-beta-Gal) staining and gammaH2AX-positive decidual cells. Interestingly, increased endocannabinoid signaling activated MAPK p38, but not p42/44 or mTORC1 signaling, inFaah(-/-)deciduae, and inhibition of p38 halted premature decidual senescence. We further showed that treatment of a long-acting anandamide in wild-type mice at midgestation triggered premature decidual senescence utilizing CB1, since administration of a CB1 antagonist greatly reduced the rate of PTB inFaah(-/ )females exposed to LPS. These results provide evidence that endocannabinoid signaling is critical in regulating decidual senescence and parturition timing. This study identifies a previously unidentified pathway in decidual senescence, which is independent of mTORC1 signaling. PMID- 26900151 TI - Ligand Binding Induces Conformational Changes in Human Cellular Retinol-binding Protein 1 (CRBP1) Revealed by Atomic Resolution Crystal Structures. AB - Important in regulating the uptake, storage, and metabolism of retinoids, cellular retinol-binding protein 1 (CRBP1) is essential for trafficking vitamin A through the cytoplasm. However, the molecular details of ligand uptake and targeted release by CRBP1 remain unclear. Here we report the first structure of CRBP1 in a ligand-free form as well as ultra-high resolution structures of this protein bound to either all-trans-retinol or retinylamine, the latter a therapeutic retinoid that prevents light-induced retinal degeneration. Superpositioning of human apo- and holo-CRBP1 revealed major differences within segments surrounding the entrance to the retinoid-binding site. These included alpha-helix II and hairpin turns between beta-strands betaC-betaD and betaE-betaF as well as several side chains, such as Phe-57, Tyr-60, and Ile-77, that change their orientations to accommodate the ligand. Additionally, we mapped hydrogen bond networks inside the retinoid-binding cavity and demonstrated their significance for the ligand affinity. Analyses of the crystallographic B-factors indicated several regions with higher backbone mobility in the apoprotein that became more rigid upon retinoid binding. This conformational flexibility of human apo-CRBP1 facilitates interaction with the ligands, whereas the more rigid holoprotein structure protects the labile retinoid moiety during vitamin A transport. These findings suggest a mechanism of induced fit upon ligand binding by mammalian cellular retinol-binding proteins. PMID- 26900152 TI - Insight into Structure-Function Relationships and Inhibition of the Fatty Acyl AMP Ligase (FadD32) Orthologs from Mycobacteria. AB - Mycolic acids are essential components of the mycobacterial cell envelope, and their biosynthetic pathway is one of the targets of first-line antituberculous drugs. This pathway contains a number of potential targets, including some that have been identified only recently and have yet to be explored. One such target, FadD32, is required for activation of the long meromycolic chain and is essential for mycobacterial growth. We report here an in-depth biochemical, biophysical, and structural characterization of four FadD32 orthologs, including the very homologous enzymes fromMycobacterium tuberculosisandMycobacterium marinum Determination of the structures of two complexes with alkyl adenylate inhibitors has provided direct information, with unprecedented detail, about the active site of the enzyme and the associated hydrophobic tunnel, shedding new light on structure-function relationships and inhibition mechanisms by alkyl adenylates and diarylated coumarins. This work should pave the way for the rational design of inhibitors of FadD32, a highly promising drug target. PMID- 26900153 TI - Task-Specific Dystonia in Professional Musicians. A Systematic Review of the Importance of Intensive Playing as a Risk Factor. AB - BACKGROUND: Focal dystonia in professional musicians is a movement disorder that manifests itself during playing. It is a multifactorial condition in which a genetic predisposition and exogenous factors both play a role. Evidence suggests that intensive playing is a risk factor for the development of task-specific dystonia in professional musicians. METHODS: This review is based on pertinent publications (1950-2013) retrieved by a systematic search in medical and musicological databases. The references of the retrieved publications were also considered in the search. RESULTS: 16 articles with clinical information on a total of 1144 affected musicians were reviewed systematically. Their overall quality was intermediate to poor, and a meta-analysis was therefore not possible. The Bradford Hill criteria were applied to study a possible causative link between intensive playing and musician's dystonia. Musician's dystonia generally arises after at least ten years of intensive playing (corresponding to roughly 10 000 hours of practice). An association was found between the affected limb and the type of instrument: the limb that is subject to the greatest fine motor demands is the one most commonly affected. The average age of onset is 28 to 44 years. CONCLUSION: The Bradford Hill causality criteria indicate that intensive playing is related to the development of musician's dystonia. In particular, the association of the type of instrument with the site of dystonia supports this thesis. The findings imply that task-specific dystonia in professional musicians should be included in the list of occupational diseases in Germany. PMID- 26900155 TI - The Treatment of Autosomal Dominant Polycystic Kidney Disease. AB - BACKGROUND: About one in 2000 persons in Europe suffers from autosomal dominant polycystic kidney disease (ADPKD). The treatment of this disease up to the present has been limited to the management of complications. METHODS: This review is based on pertinent publications, mostly of the last three years, that were retrieved by a selective search in PubMed. RESULTS: Kidney volume is probably the most important predictive factor for the loss of renal function. A measurement of kidney size is, therefore, recommended as soon as the diagnosis is made. ADPKD patients under age 30 with a combined kidney volume above 1500 mL and an estimated glomerular filtration rate (eGFR) below 90 mL/min are at high risk of needing kidney-replacement therapy (dialysis or transplantation) within 20 years, even if their renal function is normal. Ultrasonographic follow-up can identify affected persons whose risk for rapid progression is especially high. Currently available evidence reveals that, in patients at risk whose renal function is normal, the maintenance of blood pressure at or below a target value of 110/75 mmHg lessens renal enlargement, albuminuria, and left-ventricular hypertrophy. In another study, the treatment of selected patients with tolvaptan, a vasopressin-2 receptor (V2R) blocker, was found to delay cyst enlargement and the related decline in renal function for three years. It is unclear, however, how long the effect of tolvaptan persists, or whether persons whose renal function is already impaired can benefit from it. The main side effects are marked polyuria and, in rare cases, liver toxicity. CONCLUSION: In patients with ADPKD, an effort should be made to keep the arterial blood pressure below 120/80 mmHg. In patients at high risk of progression whose renal function is still intact (eGFR > 60 mL/min), strict blood pressure control (< 110/75 mm Hg) is indicated, and possibly V2R blockade with tolvaptan as well. Tolvaptan is an expensive drug, and patients taking it must be carefully monitored for hepatotoxicity. PMID- 26900154 TI - The Effects of Climate Change on Patients With Chronic Lung Disease. A Systematic Literature Review. AB - BACKGROUND: Ever since higher overall mortality rates due to heat stress were reported during the European heat waves of 2003 and 2006, the relation between heat waves and disease-specific events has been an object of scientific study. The effects of heat waves on the morbidity and mortality of persons with chronic lung disease remain unclear. METHODS: We conducted a systematic search using PubMed, the Cochrane Library, and Google Advanced Search to identify relevant studies published between 1990 and 2015. The reference lists of the primarily included articles were searched for further pertinent articles. All articles were selected according to the PRISMA guidelines. The heat-wave-related relative excess mortality was descriptively expressed as a mean daily rate ratio ([incidence 1]/[incidence 2]), and the cumulative excess risk (CER) was expressed in percent. RESULTS: 33 studies with evaluable raw data concerning the effect of heat waves on patients with chronic lung disease (chronic obstructive pulmonary disease, bronchial asthma, pulmonary arterial hypertension, and idiopathic pulmonary fibrosis) were analyzed in this review. By deriving statistics from the overall data set, we arrived at the conclusion that future heat waves will-with at least 90% probability-result in a mean daily excess mortality (expressed as a rate ratio) of at least 1.018, and-with 50% probability-in a mean daily excess mortality of at least 1.028. These figures correspond, respectively, to 1.8% and 2.8% rises in the daily risk of death. CONCLUSION: Heat waves significantly increase morbidity and mortality in patients with chronic lung disease. The argument that the excess mortality during heat waves is compensated for by a decrease in mortality in the subsequent weeks/months (mortality displacement) should not be used as an excuse for delay in implementing adaptive strategies to protect lung patients from this risk to their health. PMID- 26900157 TI - Hoarseness Caused by Glucocorticoids. PMID- 26900156 TI - The Differential Diagnosis and Treatment of Atypical Parkinsonism. AB - BACKGROUND: Aside from idiopathic Parkinson syndrome (Parkinson's disease), there are a number of other, so-called atypical parkinsonian syndromes: dementia with Lewy bodies (DLB), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). DLB is a common disease, with a prevalence of 0.4% (400 cases per 100 000 persons) in the elderly; MSA and PSP both have a prevalence of 5 to 10 per 100 000 persons, while the prevalence of CBD is about 1 per 100 000. METHODS: This review is based on pertinent publications retrieved by a selective literature search. RESULTS: The atypical parkinsonian syndromes are synucleinopathies and tauopathies, i.e., disorders characterized by the abnormal deposition of the proteins alpha-synuclein and tau. The site of deposition is correlated with the clinical features. In DLB, synuclein is mainly deposited in neocortical neurons, with some brain stem involvement as well. The main clinical features are dementia and, later on, parkinsonism. In MSA, synuclein is deposited in oligodendrocytes, mainly in the cerebellum but also in the brain stem; the main clinical feature is autonomic dysfunction combined with parkinsonism or cerebellar ataxia. Synucleinopathies often impair REM (rapid eye movement) sleep. PSP and CBD, on the other hand, are primary tauopathies. PSP usually causes predominantly supranuclear vertical gaze palsy and early postural instability with falls, less commonly parkinsonism (PSP P) or frontotemporal dementia (PSP-FTD) as its most prominent feature. CBD typically manifests itself as markedly asymmetrical parkinsonism with apraxia or cortical sensory disturbance. At present, there is no accepted causal treatment for any of these disorders; the available symptomatic treatments are of limited efficacy and are supported only by low-level evidence. CONCLUSION: Causal treatments for neurodegenerative diseases are now being developed and tested, and thus a molecular diagnosis is desirable. This will require the cooperation of primary care physicians with specialized centers. PMID- 26900158 TI - Rule out Cancer Early. PMID- 26900159 TI - In Reply. PMID- 26900160 TI - Inflammatory Bowel Disease. AB - BACKGROUND: Inflammatory bowel diseases are common in Europe, with prevalences as high as 1 in 198 persons (ulcerative colitis) and 1 in 310 persons (Crohn's disease). METHODS: This review is based on pertinent articles retrieved by a search in PubMed and in German and European guidelines and Cochrane reviews of controlled trials. RESULTS: Typically, the main clinical features of inflammatory bowel diseases are diarrhea, abdominal pain, and, in the case of ulcerative colitis, peranal bleeding. These diseases are due to a complex immunological disturbance with both genetic and environmental causes. A defective mucosal barrier against commensal bowel flora plays a major role in their pathogenesis. The diagnosis is based on laboratory testing, ultrasonography, imaging studies, and, above all, gastrointestinal endoscopy. Most patients with Crohn's disease respond to budesonide or systemic steroids; aminosalicylates are less effective. Refractory exacerbations may be treated with antibodies against tumor necrosis factor (TNF) or, more recently, antibodies against integrin, a protein of the cell membrane. In ulcerative colitis, aminosalicylates are given first; if necessary, steroids or antibodies against TNF-alpha or integrin are added. Maintenance therapy to prevent further relapses often involves immunosuppression with thiopurines and/or antibodies. Once all conservative treatment options have been exhausted, surgery may be necessary. CONCLUSION: The treatment of chronic inflammatory bowel diseases requires individually designed therapeutic strategies and the close interdisciplinary collaboration of internists and surgeons. PMID- 26900162 TI - Determination of the Stoichiometry of the Complete Bacterial Type III Secretion Needle Complex Using a Combined Quantitative Proteomic Approach. AB - Precisely knowing the stoichiometry of their components is critical for investigating structure, assembly, and function of macromolecular machines. This has remained a technical challenge in particular for large, hydrophobic membrane spanning protein complexes. Here, we determined the stoichiometry of a type III secretion system of Salmonella enterica serovar Typhimurium using two complementary protocols of gentle complex purification combined with peptide concatenated standard and synthetic stable isotope-labeled peptide-based mass spectrometry. Bacterial type III secretion systems are cell envelope-spanning effector protein-delivery machines essential for colonization and survival of many Gram-negative pathogens and symbionts. The membrane-embedded core unit of these secretion systems, termed the needle complex, is composed of a base that anchors the machinery to the inner and outer membranes, a hollow filament formed by inner rod and needle subunits that serves as conduit for substrate proteins, and a membrane-embedded export apparatus facilitating substrate translocation. Structural analyses have revealed the stoichiometry of the components of the base, but the stoichiometry of the essential hydrophobic export apparatus components and of the inner rod protein remain unknown. Here, we provide evidence that the export apparatus of type III secretion systems contains five SpaP, one SpaQ, one SpaR, and one SpaS. We confirmed that the previously suggested stoichiometry of nine InvA is valid for assembled needle complexes and describe a loose association of InvA with other needle complex components that may reflect its function. Furthermore, we present evidence that not more than six PrgJ form the inner rod of the needle complex. Providing this structural information will facilitate efforts to obtain an atomic view of type III secretion systems and foster our understanding of the function of these and related flagellar machines. Given that other virulence-associated bacterial secretion systems are similar in their overall buildup and complexity, the presented approach may also enable their stoichiometry elucidation. PMID- 26900161 TI - Lactosylceramide contributes to mitochondrial dysfunction in diabetes. AB - Sphingolipids have been implicated as key mediators of cell-stress responses and effectors of mitochondrial function. To investigate potential mechanisms underlying mitochondrial dysfunction, an important contributor to diabetic cardiomyopathy, we examined alterations of cardiac sphingolipid metabolism in a mouse with streptozotocin-induced type 1 diabetes. Diabetes increased expression of desaturase 1, (dihydro)ceramide synthase (CerS)2, serine palmitoyl transferase 1, and the rate of ceramide formation by mitochondria-resident CerSs, indicating an activation of ceramide biosynthesis. However, the lack of an increase in mitochondrial ceramide suggests concomitant upregulation of ceramide-metabolizing pathways. Elevated levels of lactosylceramide, one of the initial products in the formation of glycosphingolipids were accompanied with decreased respiration and calcium retention capacity (CRC) in mitochondria from diabetic heart tissue. In baseline mitochondria, lactosylceramide potently suppressed state 3 respiration and decreased CRC, suggesting lactosylceramide as the primary sphingolipid responsible for mitochondrial defects in diabetic hearts. Moreover, knocking down the neutral ceramidase (NCDase) resulted in an increase in lactosylceramide level, suggesting a crosstalk between glucosylceramide synthase- and NCDase mediated ceramide utilization pathways. These data suggest the glycosphingolipid pathway of ceramide metabolism as a promising target to correct mitochondrial abnormalities associated with type 1 diabetes. PMID- 26900164 TI - Featured Article: Genotation: Actionable knowledge for the scientific reader. AB - We present an article viewer application that allows a scientific reader to easily discover and share knowledge by linking genomics-related concepts to knowledge of disparate biomedical databases. High-throughput data streams generated by technical advancements have contributed to scientific knowledge discovery at an unprecedented rate. Biomedical Informaticists have created a diverse set of databases to store and retrieve the discovered knowledge. The diversity and abundance of such resources present biomedical researchers a challenge with knowledge discovery. These challenges highlight a need for a better informatics solution. We use a text mining algorithm, Genomine, to identify gene symbols from the text of a journal article. The identified symbols are supplemented with information from the GenoDB knowledgebase. Self-updating GenoDB contains information from NCBI Gene, Clinvar, Medgen, dbSNP, KEGG, PharmGKB, Uniprot, and Hugo Gene databases. The journal viewer is a web application accessible via a web browser. The features described herein are accessible on www.genotation.org The Genomine algorithm identifies gene symbols with an accuracy shown by .65 F-Score. GenoDB currently contains information regarding 59,905 gene symbols, 5633 drug-gene relationships, 5981 gene-disease relationships, and 713 pathways. This application provides scientific readers with actionable knowledge related to concepts of a manuscript. The reader will be able to save and share supplements to be visualized in a graphical manner. This provides convenient access to details of complex biological phenomena, enabling biomedical researchers to generate novel hypothesis to further our knowledge in human health. This manuscript presents a novel application that integrates genomic, proteomic, and pharmacogenomic information to supplement content of a biomedical manuscript and enable readers to automatically discover actionable knowledge. PMID- 26900165 TI - Investigating the impact of missense mutations in hCES1 by in silico structure based approaches. AB - Genetic variations in drug-metabolizing enzymes have been reported to influence pharmacokinetics, drug dosage, and other aspects that affect therapeutic outcomes. Most particularly, non-synonymous single-nucleotide polymorphisms (nsSNPs) resulting in amino acid changes disrupt potential functional sites responsible for protein activity, structure, or stability, which can account for individual susceptibility to disease and drug response. Investigating the impact of nsSNPs at a protein's structural level is a key step in understanding the relationship between genetic variants and the resulting phenotypic changes. For this purpose, in silico structure-based approaches have proven their relevance in providing an atomic-level description of the underlying mechanisms. The present review focuses on nsSNPs in human carboxylesterase 1 (hCES1), an enzyme involved in drug metabolism. We highlight how prioritization of functional nsSNPs through computational prediction techniques in combination with structure-based approaches, namely molecular docking and molecular dynamics simulations, is a powerful tool in providing insight into the underlying molecular mechanisms of nsSNPs phenotypic effects at microscopic level. Examples of in silico studies of carboxylesterases (CESs) are discussed, ranging from exploring the effect of mutations on enzyme activity to predicting the metabolism of new hCES1 substrates as well as to guiding rational design of CES-selective inhibitors. PMID- 26900163 TI - European Society of Cardiology - Acute Cardiovascular Care Association position paper on safe discharge of acute heart failure patients from the emergency department. AB - Heart failure is a global public health challenge frequently presenting to the emergency department. After initial stabilization and management, one of the most important decisions is to determine which patients can be safely discharged and which require hospitalization. This is a complex decision that depends on numerous subjective factors, including both the severity of the patient's underlying condition and an estimate of the acuity of the presentation. An emergency department observation period may help select the correct option. Ideally, during an observation period, risk stratification should be carried out using parameters specifically designed for use in the emergency department. Unfortunately, there is little objective literature to guide this disposition decision. An objective and reliable definition of low-risk characteristics to identify early discharge candidates is needed. Benchmarking outcomes in patients discharged from the emergency department without hospitalization could aid this process. Biomarker determinations, although undoubtedly useful in establishing diagnosis and predicting longer-term prognosis, require prospective validation for emergency department disposition guidance. The challenge of identifying emergency department acute heart failure discharge candidates will only be overcome by future multidisciplinary research defining the current knowledge gaps and identifying potential solutions. PMID- 26900167 TI - EARLY LIFE RISKS, ANTISOCIAL TENDENCIES, AND PRETEEN DELINQUENCY. AB - Early age-of-onset delinquency and substance use confer a major risk for continued criminality, alcohol and drug abuse, and other serious difficulties throughout the life course. Our objective is to examine the developmental roots of preteen delinquency and substance use. Using nationally representative longitudinal data from the UK Millennium Cohort Study (n = 13,221), we examine the influence of early childhood developmental and family risks on latent pathways of antisocial tendencies from ages 3 to 7, and the influence of those pathways on property crime and substance use by age 11. We identified a normative, non-antisocial pathway; a pathway marked by oppositional behavior and fighting; a pathway marked by impulsivity and inattention; and a rare pathway characterized by a wide range of antisocial tendencies. Children with developmental and family risks that emerged by age 3-specifically difficult infant temperament, low cognitive ability, weak parental closeness, and disadvantaged family background-face increased odds of antisocial tendencies. There is minimal overlap between the risk factors for early antisocial tendencies and those for preteen delinquency. Children on an antisocial pathway are more likely to engage in preteen delinquency and substance use by age 11, even after accounting for early life risk factors. PMID- 26900166 TI - The misbehaviour of a metacognitive monkey. AB - Metacognition, the monitoring of one's own mental states, is a fundamental aspect of human intellect. Despite tests in nonhuman animals suggestive of uncertainty monitoring, some authors interpret these results solely in terms of primitive psychological mechanisms and reinforcement regimes, where "reinforcement" is invariably considered to be the delivery and consumption of earned food rewards. Surprisingly, few studies have detailed the trial-by-trial behaviour of animals engaged in such tasks. Here we report ethology-based observations on a rhesus monkey completing sparse-dense discrimination problems, and given the option of escaping trials (i.e., responding "uncertain") at its own choosing. Uncertainty responses were generally made on trials of high objective difficulty, and were characterized by long latencies before beginning visible trials, long times taken for response, and, even after controlling for difficulty, high degrees of wavering during response. Incorrect responses were also common in trials of high objective difficulty, but were characterized by low degrees of wavering. This speaks to the likely adaptive nature of "hesitation," and is inconsistent with models which argue or predict implicit, inflexible information-seeking or "alternative option" behaviours whenever challenging problems present themselves, Confounding models which suggest that nonhuman behaviour in metacognition tasks is driven solely by food delivery/consumption, the monkey was also observed allowing pellets to accumulate and consuming them during and after trials of all response/outcome categories (i.e., whether correct, incorrect, or escaped). This study thus bolsters previous findings that rhesus monkey behaviour in metacognition tasks is in some respects disassociated from mere food delivery/consumption, or even the avoidance of punishment. These and other observations fit well with the evolutionary status and natural proclivities of rhesus monkeys, but weaken arguments that responses in such tests are solely associated with associative mechanisms, and instead suggest more derived and controlled cognitive processing. The latter interpretation appears particularly parsimonious given the neurological adaptations of primates, as well as their highly flexible social and ecological behaviour. PMID- 26900168 TI - Consciousness. AB - No one did more to draw neuroscientists' attention to the problem of consciousness in the twentieth century than Francis Crick, who may be better known as the co-discoverer (with James Watson) of the structure of DNA. Crick focused his research on visual awareness and based his analysis on the progress made over the last fifty years in uncovering the neural mechanisms underlying visual perception. Because much of what happens in our brains occurs below the level of consciousness and many of our intuitions about unconscious processing are misleading, consciousness remains an elusive problem. In the end, when all of the brain mechanisms that underlie consciousness have been identified, will we still be asking: "What is consciousness?" Or will the question shift, just as the question "What is life?" is no longer the same as it was before Francis Crick? PMID- 26900169 TI - Urban inoculation and the decline of smallpox mortality in eighteenth-century cities-a reply to Razzell. AB - Smallpox was probably the single most lethal disease in eighteenth-century Britain but was reduced to a minor cause of death by the mid-nineteenth century due to vaccination programmes post-1798. While the success of vaccination is unquestionable, it remains disputed to what extent the prophylactic precursor of vaccination, inoculation, reduced smallpox mortality in the eighteenth century. Smallpox was most lethal in urban populations, but most researchers have judged inoculation to have been unpopular in large towns. Recently, however, Razzell argued that inoculation significantly reduced smallpox mortality of adults and older children in London in the last third of the eighteenth century. This article uses demographic evidence from London and Manchester to confirm previous findings of a sudden fall in adult smallpox mortality and a rise in the importance of smallpox in early childhood c. 1770. The nature of these changes is consistent with an increase in smallpox transmission in London and Manchester after 1770 and indicates that smallpox inoculation was insufficient to reduce smallpox mortality in large towns. It remains unclear whether inoculation could have operated to enhance smallpox transmission or whether changes in the properties of the smallpox virus drove the intensification of smallpox mortality among young children post-1770. PMID- 26900171 TI - Symmetrical and asymmetrical outcomes of leader anger expression: A qualitative study of army personnel. AB - Recent studies have highlighted the utility of anger at work, suggesting that anger can have positive outcomes. Using the Dual Threshold Model, we assess the positive and negative consequences of anger expressions at work and focus on the conditions under which expressions of anger crossing the impropriety threshold are perceived as productive or counterproductive by observers or targets of that anger. To explore this phenomenon, we conducted a phenomenological study (n = 20) to probe the lived experiences of followers (as observers and targets) associated with anger expressions by military leaders. The nature of task (e.g. the display rules prescribed for combat situations) emerged as one condition under which the crossing of the impropriety threshold leads to positive outcomes of anger expressions. Our data reveal tensions between emotional display rules and emotional display norms in the military, thereby fostering paradoxical attitudes toward anger expression and its consequences among followers. Within this paradoxical space, anger expressions have both positive (asymmetrical) and negative (symmetrical) consequences. We place our findings in the context of the Dual Threshold Model, discuss the practical implications of our research and offer avenues for future studies. PMID- 26900170 TI - Durable resistance to the wheat rusts: Integrating systems biology and traditional phenotype-based research methods to guide the deployment of resistance genes. AB - Genes which confer partial resistance to the rusts in wheat figure prominently in discussions of potential durable resistance strategies. The positional cloning of the first of these genes, Lr34/Yr18 and Yr36, has revealed different protein structures, suggesting that the category of partial resistance genes, as defined by phenotype, likely groups together suites of functionally heterogenous genes. With the number of mapped partial rust resistance genes increasing rapidly as a result of ongoing advances in marker and sequencing technologies, breeding programs needing to select and prioritize genes for deployment confront a fundamental question: which genes or gene combinations are more likely to provide durable protection against these evolving pathogens? We argue that a refined classification of partial rust resistance genes is required to start answering this question, one based not merely on disease phenotype but also on gene cloning, molecular functional characterization, and interactions with other host and pathogen proteins. Combined with accurate and detailed disease phenotyping and standard genetic studies, an integrated wheat-rust interactome promises to provide the basis for a functional classification of partial resistance genes and thus a conceptual framework for their rational deployment. PMID- 26900172 TI - Anthropic Correction of Information Estimates and Its Application to Neural Coding. AB - Information theory has been used as an organizing principle in neuroscience for several decades. Estimates of the mutual information (MI) between signals acquired in neurophysiological experiments are believed to yield insights into the structure of the underlying information processing architectures. With the pervasive availability of recordings from many neurons, several information and redundancy measures have been proposed in the recent literature. A typical scenario is that only a small number of stimuli can be tested, while ample response data may be available for each of the tested stimuli. The resulting asymmetric information estimation problem is considered. It is shown that the direct plug-in information estimate has a negative bias. An anthropic correction is introduced that has a positive bias. These two complementary estimators and their combinations are natural candidates for information estimation in neuroscience. Tail and variance bounds are given for both estimates. The proposed information estimates are applied to the analysis of neural discrimination and redundancy in the avian auditory system. PMID- 26900173 TI - Child development accounts (CDAs): An asset-building strategy to empower girls in Uganda. AB - This study explores an innovative intervention for orphaned children in Uganda. It combines standard health care with an economic empowerment component. We refer to this combination as a family asset-based intervention, which provides each child with a child development account (CDA), a matched savings account for secondary schooling; financial education; and a mentor. This article examines the educational outcomes of the girls in this study. The results from the first two waves of the study indicate that CDAs have the potential to begin to help negate the effects of past gender inequalities and to help provide a path for young girls to move forward. PMID- 26900174 TI - Rehabilitating the cyanobacteria - niche partitioning, resource use efficiency and phytoplankton community structure during diazotrophic cyanobacterial blooms. AB - Blooms of nitrogen-fixing cyanobacteria are recurrent phenomena in marine and freshwater habitats, and their supplying role in aquatic biogeochemical cycles is generally considered vital. The objective of this study was to analyse whether an increasing proportion of nitrogen-fixing cyanobacteria affects (i) the composition of the non-diazotrophic component of ambient phytoplankton communities and (ii) resource use efficiency (RUE; ratio of Chl a to total nutrients) - an important ecosystem function. We hypothesize that diazotrophs increase community P use and decrease N use efficiencies, as new N is brought into the system, relaxing N, and concomitantly aggravating P limitation. We test this by analysing an extensive data set from the Baltic Sea (> 3700 quantitative phytoplankton samples), known to harbour conspicuous and recurrent blooms of Nodularia spumigena and Aphanizomenon sp.System-level phosphorus use efficiency (RUEP) was positively related to high proportion of diazotrophic cyanobacteria, suggesting aggravation of phosphorus limitation. However, concomitant decrease of nitrogen use efficiency (RUEN) was not observed. Nodularia spumigena, a dominant diazotroph and a notorious toxin producer, had a significantly stronger relationship with RUEP, compared to the competing non-toxic Aphanizomenon sp., confirming niche differentiation in P acquisition strategies between the major bloom-forming cyanobacterial species in the Baltic Sea. Nodularia occurrences were associated with stronger temperature stratification in more offshore environments, indicating higher reliance on in situ P regeneration.By using constrained and unconstrained ordination, permutational multivariate analysis of variance and local similarity analysis, we show that diazotrophic cyanobacteria explained no more than a few percentage of the ambient phytoplankton community variation. The analyses furthermore yielded rather evenly distributed negative and positive effects on individual co-occurring phytoplankton taxa, with no obvious phylogenetic or functional trait-based patterns. Synthesis. Our study reveals that despite the widely acknowledged noxious impacts of cyanobacterial blooms, the overall effect on phytoplankton community structure is minor. There are no predominantly positive or negative associations with ambient phytoplankton species. Species-specific niche differences in cyanobacterial resource acquisition affect important ecosystem functions, such as biomass production per unit limiting resource. PMID- 26900175 TI - Scaling solution in the large population limit of the general asymmetric stochastic Luria-Delbruck evolution process. AB - One of the most popular models for quantitatively understanding the emergence of drug resistance both in bacterial colonies and in malignant tumors was introduced long ago by Luria and Delbruck. Here, individual resistant mutants emerge randomly during the birth events of an exponentially growing sensitive population. A most interesting limit of this process occurs when the population size N is large and mutation rates are low, but not necessarily small compared to 1/N. Here we provide a scaling solution valid in this limit, making contact with the theory of Levy alpha-stable distributions, in particular one discussed long ago by Landau. One consequence of this association is that moments of the distribution are highly misleading as far as characterizing typical behavior. A key insight that enables our solution is that working in the fixed population size ensemble is not the same as working in a fixed time ensemble. Some of our results have been presented previously in shortened form [11]. PMID- 26900176 TI - Indirect effects of red imported fire ants on Attwater's prairie-chicken brood survival. AB - The invasive red imported fire ant (Solenopsis invicta) has negatively affected a host of taxonomic groups throughout its acquired North American range. Many studies have hypothesized indirect trophic impacts, but few documented those impacts. We evaluated invertebrate abundance as a factor limiting juvenile survival of the endangered Attwater's prairie-chicken (Tympanuchus cupido attwateri), and whether fire ants reduce invertebrate numbers and biomass. From 2009-2013, we monitored survival of Attwater's prairie-chicken broods (n = 63) with radio telemetry during the first 2 weeks post-hatch and collected daily invertebrate samples at brood sites. Broods located in areas with the highest median invertebrate count (338 invertebrates/25 sweeps) had a survival probability of 0.83 at 2 weeks post-hatch compared to 0.07 for broods located in areas with the lowest median invertebrate count (18 invertebrates/25 sweeps). During 2011-2012, we evaluated the reduction of fire ants on invertebrate numbers and biomass by aerially treating areas with Extinguish PlusTM in an impact reference study design. Treated fields had 27% more individual invertebrates and 26% higher invertebrate biomass than reference fields. Our results clearly document that invertebrate abundance affects Attwater's prairie-chicken brood survival and that fire ants may indirectly contribute to low brood survival by suppressing invertebrate abundance. We posit that within the fire ant's acquired North American range, fire ants are likely contributing to declines of other insectivorous species. Published 2015. This article is a U.S. Government work and is in the public domain in the USA. PMID- 26900178 TI - The calcareous brown alga Padina pavonica in southern Britain: population change and tenacity over 300 years. AB - Understanding long-term persistence and variability in species populations can help to predict future survival, growth and distribution; however, sustained observations are exceedingly rare. We examine and interpret a remarkable record of the calcareous brown alga Padina pavonica (Phaeophyceae) at its northern limit on the south coast of England (50 degrees N, 1-3 degrees W) from 1680 to 2014, which is probably the longest compilation and review of any marine algal species. Over this period, which extends from the middle of the Little Ice Age to the present, there has been considerable variability in temperature and storminess. We identified a significant number of site extinctions in the second half of the nineteenth century, which coincided with cooler conditions and stormier weather. To interpret these changes, we measured recruitment, growth and production of tetraspores at sheltered and exposed sites in 2012-2014, years which had low and high spring temperatures. Potential spore production was greater at the sheltered site due to a longer growing period and survival of larger fronds. Delayed growth in the cooler spring resulted in smaller fronds and lower potential production of tetraspores by early summer. Yet in the warmer year, rapid initial growth caused higher sensitivity to damage and dislodgement by summer storms, which also limited potential spore production. Antagonistic responses to multiple stressors and disturbances make future predictions of survival and distribution difficult. Fronds of Padinapavonica are sensitive to both temperature and physical disturbances, yet vegetative perennation appears to have enabled population persistence and explained the longevity of remaining populations. PMID- 26900177 TI - Remarkable ancient divergences amongst neglected lorisiform primates. AB - Lorisiform primates (Primates: Strepsirrhini: Lorisiformes) represent almost 10% of the living primate species and are widely distributed in sub-Saharan Africa and South/South-East Asia; however, their taxonomy, evolutionary history, and biogeography are still poorly understood. In this study we report the largest molecular phylogeny in terms of the number of represented taxa. We sequenced the complete mitochondrial cytochrome b gene for 86 lorisiform specimens, including ~80% of all the species currently recognized. Our results support the monophyly of the Galagidae, but a common ancestry of the Lorisinae and Perodicticinae (family Lorisidae) was not recovered. These three lineages have early origins, with the Galagidae and the Lorisinae diverging in the Oligocene at about 30 Mya and the Perodicticinae emerging in the early Miocene. Our mitochondrial phylogeny agrees with recent studies based on nuclear data, and supports Euoticus as the oldest galagid lineage and the polyphyletic status of Galagoides. Moreover, we have elucidated phylogenetic relationships for several species never included before in a molecular phylogeny. The results obtained in this study suggest that lorisiform diversity remains substantially underestimated and that previously unnoticed cryptic diversity might be present within many lineages, thus urgently requiring a comprehensive taxonomic revision of this primate group. PMID- 26900179 TI - Metrological challenges for measurements of key climatological observables: Oceanic salinity and pH, and atmospheric humidity. Part 1: Overview. AB - Water in its three ambient phases plays the central thermodynamic role in the terrestrial climate system. Clouds control Earth's radiation balance, atmospheric water vapour is the strongest "greenhouse" gas, and non-equilibrium relative humidity at the air-sea interface drives evaporation and latent heat export from the ocean. On climatic time scales, melting ice caps and regional deviations of the hydrological cycle result in changes of seawater salinity, which in turn may modify the global circulation of the oceans and their ability to store heat and to buffer anthropogenically produced carbon dioxide. In this paper, together with three companion articles, we examine the climatologically relevant quantities ocean salinity, seawater pH and atmospheric relative humidity, noting fundamental deficiencies in the definitions of those key observables, and their lack of secure foundation on the International System of Units, the SI. The metrological histories of those three quantities are reviewed, problems with their current definitions and measurement practices are analysed, and options for future improvements are discussed in conjunction with the recent seawater standard TEOS 10. It is concluded that the International Bureau of Weights and Measures, BIPM, in cooperation with the International Association for the Properties of Water and Steam, IAPWS, along with other international organisations and institutions, can make significant contributions by developing and recommending state-of-the-art solutions for these long standing metrological problems in climatology. PMID- 26900180 TI - Contrasting temperature responses of dissolved organic carbon and phenols leached from soils. AB - BACKGROUND AND AIMS: Plant-derived phenols are a major input to the terrestrial carbon cycle that might be expected to contribute substantially to dissolved organic carbon (DOC) losses from soils. This study investigated changes in DOC and phenols in leachates from soil treated with individual plant litter types under seasonal temperature change. METHODS: Senescing grass, buttercup, ash and oak litters were applied to soil lysimeters. Leachates were collected over 22 months and analysed for DOC and phenols. Phenols in litter and DOC were analysed using on-line thermally assisted hydrolysis and methylation with tetramethylammonium hydroxide (TMAH). RESULTS: Mass loss differed between litter type (buttercup>ash>grass>oak). Phenol concentrations in the senescing litters (<2 % TOC) were small, resulting in minor losses to water. Seasonal soil temperature positively correlated with DOC loss from litter-free soils. An initial correlation between temperature change and total phenol concentration in grass and ash litter treatment leachates diminished with time. Dissolved phenol variety in all litter-amended soil leachates increased with time. CONCLUSIONS: Plant-derived phenols from senescing litter made a minor contribution to DOC loss from soils. The strength of the relationship between seasonal temperature change and phenol type and abundance in DOC changed with time and was influenced by litter type. PMID- 26900181 TI - The influence of negative response style on survey-based household inflation expectations. AB - The study identified a sub-group of respondents adopting a negative response style in consumer tendency surveys and investigated their influence on aggregate household inflation expectations. Households prone to negative response style were identified using multi-group latent class models. The data source was the State of the Household Survey, conducted following European Commission methodology, in Poland between 1999 and 2010 (45 quarters). Although group size for households with negative response style was shown to fluctuate, negative response was comparable between periods. Micro-level information on response style was used to correct inflation expectations by the creation of additional factors for respondent weights. After compensation: (1) respondent inflation expectations proved more consistent with professional forecasts; (2) there was significantly better correlation between inflation expectations and consumer confidence; (3) compensated inflation expectations demonstrated the Ball-Friedman hypothesis; whereas, this pattern did not emerge for uncorrected data. Of the available household characteristics, income and age were the only significant determinants for negative response style. PMID- 26900182 TI - Exploring Teacher Intervention in the Intersection of Digital Resources, Peer Collaboration, and Instructional Design. AB - This paper reports on a case study of the teacher's role as facilitator in computer-supported collaborative learning (CSCL) settings in science. In naturalistic classroom settings, the teacher most often acts as an important resource and provides various forms of guidance during students' learning activities. Few studies, however, have focused on the role of teacher intervention in CSCL settings. By analyzing the interactions between secondary school students and their teacher during a science project, the current study provides insight into the concerns that teachers might encounter when facilitating students' learning processes in these types of settings. The analyses show that one main concern was creating a balance between providing the requested information and supporting students in utilizing each other's knowledge and understanding. Another concern was balancing support on an individual versus group level, and a third concern was directing the students' attention to coexisting conceptual perspectives. Most importantly, however, the analyses show how teacher intervention constitutes the pivotal "glue" that aids students in linking and using coexisting aspects of support such as peer collaboration, digital tools, and instructional design. PMID- 26900183 TI - The emergence of hydrogeophysics for improved understanding of subsurface processes over multiple scales. AB - A review of the emergence and development of hydrogeophysicsOutline of emerging techniques in hydrogeophysicsPresentation of future opportunities in hydrogeophysics. PMID- 26900184 TI - Uncertainty in global groundwater storage estimates in a Total Groundwater Stress framework. AB - Groundwater resilience is defined and quantified with remote sensing from GRACETimescales of aquifer depletion are assessed as a Total Groundwater Stress ratioThe volume of usable global groundwater storage is found to be largely unknown. PMID- 26900185 TI - Quantifying renewable groundwater stress with GRACE. AB - Renewable groundwater stress is quantified in the world's largest aquifersCharacteristic stress regimes are defined to determine the severity of stressOverstressed aquifers are mainly in rangeland biomes with some croplands. PMID- 26900186 TI - The Dynamics and Correlates of Religious Service Attendance in Adolescence. AB - This study examines changes in religious service attendance over time for a contemporary cohort of adolescents moving from middle to late adolescence. We use two waves of a nationally representative panel survey of youth from the National Study of Youth and Religion (NSYR) to examine the dynamics of religious involvement during adolescence. We then follow with an analysis of how demographic characteristics, family background, and life course transitions relate to changes in religious service attendance during adolescence. Our findings suggest that, on average, adolescent religious service attendance declines over time, related to major life course transitions such as becoming employed, leaving home, and initiating sexual activity. Parents' affiliation and attendance, on the other hand, are protective factors against decreasing attendance. PMID- 26900187 TI - Arsenic and Lead Uptake by Vegetable Crops Grown on an Old Orchard Site Amended with Compost. AB - The potential for lead (Pb) and arsenic (As) transfer into vegetables was studied on old orchard land contaminated by lead arsenate pesticides. Root (carrot), leafy (lettuce), and vegetable fruits (green bean, tomato) were grown on seven "miniplots" with soil concentrations ranging from near background to ~ 800 and ~ 200 mg kg-1 of total Pb and As, respectively. Each miniplot was divided into sub plots and amended with 0% (control), 5% and 10% (by weight) compost and cropped for 3 years. Edible portions of each vegetable were analyzed for total Pb and As to test the effect of organic matter on transfer of these toxic elements into the crop. Vegetable Pb and As concentrations were strongly correlated to soil total Pb and As, respectively, but not to soil organic matter content or compost addition level. For Pb vegetable concentrations, carrot >= lettuce > bean > tomato. For As, lettuce > carrot > bean > tomato. A complementary single-year study of lettuce, arugula, spinach, and collards revealed a beneficial effect of compost in reducing both Pb and As concentrations in leafy vegetables. Comparisons of all measured vegetable concentrations to international health based standards indicate that tomatoes can be grown without exceeding standards even in substantially Pb- and As-contaminated soils, but carrots and leafy greens may exceed standards when grown in soils with more than 100-200 mg kg-1 Pb. Leafy greens may also exceed health-based standards in gardens where soil As is elevated, with arugula having a particularly strong tendency to accumulate As. PMID- 26900188 TI - Collective Opinion Paper on a 2013 AACB Workshop of Experts seeking Harmonisation of Approaches to Setting a Laboratory Quality Control Policy. PMID- 26900189 TI - Consensus Statement for the Management and Communication of High Risk Laboratory Results. AB - Ineffective test follow-up is a major source of harm for patients around the world. Unreliable communication from medical laboratories (henceforth termed 'laboratories') to clinicians of results that represent critical or significant risk to patients (collectively termed 'high risk results') is a contributing factor to this problem. Throughout Australasia, management practices for such results vary considerably. The recommendations presented in this document are based on best practice derived from the published literature and follow consultation with a wide range of stakeholders. These recommendations were created to harmonise Australasian practices by guiding laboratories in the design and implementation of safe and effective communication procedures for managing high risk results which require timely notification. PMID- 26900191 TI - Aspects to Consider in Adopting Pregnancy-Specific Reference Intervals. PMID- 26900192 TI - Variation in Laboratory Reporting of Haemolysis - a Need for Harmonisation. AB - AIM: The purpose of this survey was to determine the cut-offs being used by Australian laboratories using their instrument's Haemolysis Index (HI), whether these cut-offs vary, and at what level of haemolysis (or haemolysis index) did laboratories stop reporting one or more analytes. This was done in response to the large numbers of haemolysed samples reported in the RCPAQAP Key Incident Monitoring and Management System External Quality Assurance program (KIMMS EQA) and lack of information in the literature at the time regarding what to do once a haemolysed sample was identified. As it was known from discussions with laboratory personnel that different instruments reported their HI differently, we asked for the results to be provided in g/L free haemoglobin. METHOD: An electronic survey was conducted with participants enrolled in the RCPA Quality Assurance Programs with a total of 68 laboratories responding to this survey. Some questions attracted a lower level of response. RESULTS: The responses showed a poor understanding of the relationship between HI units and haemoglobin concentration. There was wide variation in the way HI results were reported and thus comparing cut-off values for reporting specific analytes based on the HI was impossible to determine. CONCLUSION: There is a need to harmonise the way laboratories report analytes in the presence of haemolysis. This would involve adopting a uniform definition of HI and a protocol for laboratories to confirm for themselves the level of HI at which each analyte is no longer reported, as this is method dependent and so will vary from laboratory to laboratory. PMID- 26900190 TI - Reporting Thyroid Function Tests in Pregnancy. AB - While there is agreement that overt maternal hypothyroidism (serum thyroid stimulating hormone (TSH) >10 mIU/L) should be treated immediately, the evidence is mixed regarding the harm associated with subclinical hypothyroidism and the benefits of thyroxine replacement. The diagnosis of subclinical hypothyroidism rests on the recognition of an increased serum concentration of TSH which may be affected by many factors including gestational age, analytical method, the antibody status of the mother, ethnicity, iodine nutrition and even the time of day when the blood is collected. The 97.5(th) percentile of TSH at the end of the first trimester is commonly used as the upper boundary of normal in early pregnancy with a default value of 2.5 mIU/L specified in a number of recent clinical guidelines. There have now been numerous papers showing that a more realistic figure is between 3.0 and 4.0 mIU/L depending on the analytical method that is used. There are suggestions that ethnicity may also have a significant effect on TSH and FT4 reference limits in pregnancy. PMID- 26900193 TI - The Academic Adaptation of Children of Immigrants in New and Established Settlement States: The Role of Family, Schools, and Neighborhoods. AB - The dispersion of immigrants has challenged educators in new immigrant destinations to adapt to the needs of their first cohorts of children of immigrants. This paper evaluates how families, schools, and neighborhoods shape the academic adaptation of immigrants' children in new and established immigrant states. Using the Educational Longitudinal Study (ELS) from 2002, the paper examines how 10th grade math and reading test scores differ across three settlement locations: established, new, and other immigrant states. Results indicate that achievement in math and reading is highest in new immigrant states. While demographic differences between settlement locations largely explained differences in achievement, families and schools in new immigrant states also strongly influenced achievement. PMID- 26900194 TI - Noise Perturbation for Supervised Speech Separation. AB - Speech separation can be treated as a mask estimation problem, where interference dominant portions are masked in a time-frequency representation of noisy speech. In supervised speech separation, a classifier is typically trained on a mixture set of speech and noise. It is important to efficiently utilize limited training data to make the classifier generalize well. When target speech is severely interfered by a nonstationary noise, a classifier tends to mistake noise patterns for speech patterns. Expansion of a noise through proper perturbation during training helps to expose the classifier to a broader variety of noisy conditions, and hence may lead to better separation performance. This study examines three noise perturbations on supervised speech separation: noise rate, vocal tract length, and frequency perturbation at low signal-to-noise ratios (SNRs). The speech separation performance is evaluated in terms of classification accuracy, hit minus false-alarm rate and short-time objective intelligibility (STOI). The experimental results show that frequency perturbation is the best among the three perturbations in terms of speech separation. In particular, the results show that frequency perturbation is effective in reducing the error of misclassifying a noise pattern as a speech pattern. PMID- 26900195 TI - Gain-Sparsity and Symmetry-Forced Rigidity in the Plane. AB - We consider planar bar-and-joint frameworks with discrete point group symmetry in which the joint positions are as generic as possible subject to the symmetry constraint. We provide combinatorial characterizations for symmetry-forced rigidity of such structures with rotation symmetry or dihedral symmetry of order 2k with odd k, unifying and extending previous work on this subject. We also explore the matroidal background of our results and show that the matroids induced by the row independence of the orbit matrices of the symmetric frameworks are isomorphic to gain sparsity matroids defined on the quotient graph of the framework, whose edges are labeled by elements of the corresponding symmetry group. The proofs are based on new Henneberg type inductive constructions of the gain graphs that correspond to the bases of the matroids in question, which can also be seen as symmetry preserving graph operations in the original graph. PMID- 26900196 TI - African American caregivers' resources for support: Implications for children's perceived support from their caregiver. PMID- 26900197 TI - Temperament disturbances measured in infancy progress to substance use disorder 20 years later. AB - OBJECTIVE: This prospective study determined whether temperament before two years of age predicts transmissible risk for substance use disorder (SUD) up to a decade later and SUD outcome in adulthood. METHOD: Boys between 10 and 12 years of age (N = 482) were tracked to age 22. The previously validated transmissible liability index (TLI) was administered at baseline, and temperament prior to two years of age was retrospectively rated. The Structured Clinical Interview for DSM III-R (SCID) was administered to document presence/absence of SUD for parents at baseline and sons at age 22. RESULTS: Path analysis revealed that number of parents with SUD predicted severity of temperament disturbance in their sons which in turn predicted TLI score at age 10-12, presaging SUD. Temperament before age two did not predict SUD at age 22. The association between number of SUD parents and transmissible risk was mediated by severity of temperament disturbance. CONCLUSION: Temperament disturbance in early childhood, reflecting quality of behavioral and emotion regulation, comprise psychological antecedents of transmissible risk for SUD. PMID- 26900199 TI - Migration and Development: A Theoretical Perspective. AB - The debate on migration and development has swung back and forth like a pendulum, from developmentalist optimism in the 1950s and 1960s, to neo-Marxist pessimism over the 1970s and 1980s, towards more optimistic views in the 1990s and 2000s. This paper argues how such discursive shifts in the migration and development debate should be primarily seen as part of more general paradigm shifts in social and development theory. However, the classical opposition between pessimistic and optimistic views is challenged by empirical evidence pointing to the heterogeneity of migration impacts. By integrating and amending insights from the new economics of labor migration, livelihood perspectives in development studies and transnational perspectives in migration studies - which share several though as yet unobserved conceptual parallels - this paper elaborates the contours of a conceptual framework that simultaneously integrates agency and structure perspectives and is therefore able to account for the heterogeneous nature of migration-development interactions. The resulting perspective reveals the naivety of recent views celebrating migration as self-help development "from below". These views are largely ideologically driven and shift the attention away from structural constraints and the vital role of states in shaping favorable conditions for positive development impacts of migration to occur. PMID- 26900198 TI - Relationship Satisfaction and Communication Among Urban Minority HIV-Positive and HIV-Negative Mothers: The Influence on Daughter's Alcohol Use. AB - Family relationships influence children's beliefs and behaviors. This work examined qualities associated with communication about alcohol among 176 mothers and the influence of this communication on daughters' alcohol use. Path analyses by maternal HIV status indicated significant differences. Relationship satisfaction was associated with self-efficacy for both HIV-positive (beta = 0.545, p < .001) and HIV-negative (beta = 0.557, p < .001) mothers. Maternal self efficacy was associated with communication for both HIV-positive (beta = 0.364, p < .01) and HIV-negative (beta = 0.310, p < .05) mothers; maternal attitudes toward alcohol use were associated with communication among HIV-negative mothers (beta = 0.20, p < .05). Relationship satisfaction was indirectly related to daughter's alcohol use in HIV-positive dyads (beta = 0.153, p < .05). In families with interfamilial and environmental stressors, investing in the mother-daughter relationship, in part by discussing issues related to alcohol use, is protective in nature. PMID- 26900200 TI - The Decade of Immigrant Dispersion and Growth: A Cohort Analysis of Children of Immigrants' Educational Experiences 1990-2002. AB - The 1990s marked the beginning of a new era of immigration in terms of volume and settlement patterns and also witnessed significant changes in the social contexts confronting immigrants. These changes could have significant repercussions for immigrant youth. While previous research on high school dropout behavior suggests immigrant youth are faring better in US schools, our research provides a less optimistic outlook. Using the National Educational Longitudinal Study (1988) and Educational Longitudinal Study (2002), we use multivariate analysis, regression decomposition and fixed effect models to examine how reading and math test scores of children of immigrants changed during the 1990s. PMID- 26900201 TI - The Representation of Agents in Auditory Verbal Hallucinations. AB - Current models of auditory verbal hallucinations (AVHs) tend to focus on the mechanisms underlying their occurrence, but often fail to address the content of the auditory experience. In other words, they tend to ask why there are AVHs at all, instead of asking why, given that there are AVHs, they have the properties that they have. One such property, which has been largely overlooked and which we will focus on here, is why the voices are often experienced as coming from (or being the voices of) agents, and often specific, individualised agents. In this article, we argue not only that the representation of agents is important in accurately describing many cases of AVH, but also that deeper reflection on what is involved in the representation of agents has potentially vital consequences for our aetiological understanding of AVH, namely, for understanding how and why AVHs come about. PMID- 26900203 TI - A Combination of Spatial and Recursive Temporal Filtering for Noise Reduction when Using Region of Interest (ROI) Fluoroscopy for Patient Dose Reduction in Image Guided Vascular Interventions with Significant Anatomical Motion. AB - Because x-ray based image-guided vascular interventions are minimally invasive they are currently the most preferred method of treating disorders such as stroke, arterial stenosis, and aneurysms; however, the x-ray exposure to the patient during long image-guided interventional procedures could cause harmful effects such as cancer in the long run and even tissue damage in the short term. ROI fluoroscopy reduces patient dose by differentially attenuating the incident x rays outside the region-of-interest. To reduce the noise in the dose-reduced regions previously recursive temporal filtering was successfully demonstrated for neurovascular interventions. However, in cardiac interventions, anatomical motion is significant and excessive recursive filtering could cause blur. In this work the effects of three noise-reduction schemes, including recursive temporal filtering, spatial mean filtering, and a combination of spatial and recursive temporal filtering, were investigated in a simulated ROI dose-reduced cardiac intervention. First a model to simulate the aortic arch and its movement was built. A coronary stent was used to simulate a bio-prosthetic valve used in TAVR procedures and was deployed under dose-reduced ROI fluoroscopy during the simulated heart motion. The images were then retrospectively processed for noise reduction in the periphery, using recursive temporal filtering, spatial filtering and a combination of both. Quantitative metrics for all three noise reduction schemes are calculated and are presented as results. From these it can be concluded that with significant anatomical motion, a combination of spatial and recursive temporal filtering scheme is best suited for reducing the excess quantum noise in the periphery. This new noise-reduction technique in combination with ROI fluoroscopy has the potential for substantial patient-dose savings in cardiac interventions. PMID- 26900202 TI - Social immunity of the family: parental contributions to a public good modulated by brood size. AB - Social immunity refers to any immune defence that benefits others, besides the individual that mounts the response. Since contributions to social immunity are known to be personally costly, they are contributions to a public good. However, individuals vary in their contributions to this public good and it is unclear why. Here we investigate whether they are responding to contributions made by others with experiments on burying beetle (Nicrophorus vespilloides) families. In this species, females, males and larvae each contribute to social immunity through the application of antimicrobial exudates upon the carrion breeding resource. We show experimentally that mothers reduce their contributions to social immunity when raising large broods, and test two contrasting hypotheses to explain why. Either mothers are treating social immunity as a public good, investing less in social immunity when their offspring collectively contribute more, or mothers are trading off investment in social immunity with investment in parental care. Overall, our experiments yield no evidence to support the existence of a trade-off between social immunity and other parental care traits: we found no evidence of a trade-off in terms of time allocated to each activity, nor did the relationship between social immunity and brood size change with female condition. Instead, and consistent with predictions from models of public goods games, we found that higher quality mothers contributed more to social immunity. Therefore our results suggest that mothers are playing a public goods game with their offspring to determine their personal contribution to the defence of the carrion breeding resource. PMID- 26900204 TI - Interactive Image Segmentation Framework Based On Control Theory. AB - Segmentation of anatomical structures in medical imagery is a key step in a variety of clinical applications. Designing a generic, automated method that works for various structures and imaging modalities is a daunting task. Instead of proposing a new specific segmentation algorithm, in this paper, we present a general design principle on how to integrate user interactions from the perspective of control theory. In this formulation, Lyapunov stability analysis is employed to design and analyze an interactive segmentation system. The effectiveness and robustness of the proposed method are demonstrated. PMID- 26900205 TI - Bioenabled SERS Substrates for Food Safety and Drinking Water Monitoring. AB - We present low-cost bioenabled surface-enhanced Raman scattering (SERS) substrates that can be massively produced in sustainable and eco-friendly methods with significant commercial potentials for the detection of food contamination and drinking water pollution. The sensors are based on diatom frustules with integrated plasmonic nanoparticles. The ultra-high sensitivity of the SERS substrates comes from the coupling between the diatom frustules and Ag nanoparticles to achieve dramatically increased local optical field to enhance the light-matter interactions for SERS sensing. We successfully applied the bioenabled SERS substrates to detect melamine in milk and aromatic compounds in water with sensitivity down to 1MUg/L. PMID- 26900206 TI - Creation and Validation of Sintered PTFE BRDF Targets & Standards. AB - Sintered polytetrafluoroethylene (PTFE) is an extremely stable, near-perfect Lambertian reflecting diffuser and calibration standard material that has been used by national labs, space, aerospace and commercial sectors for over two decades. New uncertainty targets of 2 % on-orbit absolute validation in the Earth Observing Systems community have challenged the industry to improve is characterization and knowledge of almost every aspect of radiometric performance (space and ground). Assuming "near perfect" reflectance for angular dependent measurements is no longer going to suffice for many program needs. The total hemispherical spectral reflectance provides a good mark of general performance; but, without the angular characterization of bidirectional reflectance distribution function (BRDF) measurements, critical data is missing from many applications and uncertainty budgets. Therefore, traceable BRDF measurement capability is needed to characterize sintered PTFE's angular response and provide a full uncertainty profile to users. This paper presents preliminary comparison measurements of the BRDF of sintered PTFE from several laboratories to better quantify the BRDF of sintered PTFE, assess the BRDF measurement comparability between laboratories, and improve estimates of measurement uncertainties under laboratory conditions. PMID- 26900207 TI - Design and Evaluation of a Personal Diffusion Battery. AB - A four-stage personal diffusion battery (pDB) was designed and constructed to measure submicron particle size distributions. The pDB consisted of a screen-type diffusion battery, solenoid valve system, and electronic controller. A data inversion spreadsheet was created to solve for the number median diameter (NMD), geometric standard deviation (GSD), and particle number concentration of unimodal aerosols using stage number concentrations from the pDB combined with a handheld condensation particle counter (pDB+CPC). The inversion spreadsheet included particle entry losses, theoretical penetrations across screens, the detection efficiency of the CPC, and constraints so the spreadsheet solved to values within the pDB range. Size distribution parameters (NMD, GSD, and number concentration) measured with the pDB+CPC with inversion spreadsheet were within 25% of those measured with a scanning mobility particle sizer (SMPS) for 5 of 12 polydisperse combustion aerosols. For three tests conducted with propylene torch exhaust, the pDB+CPC with inversion spreadsheet successfully identified that the NMD was smaller than the constraint value of 16 nm. The ratio of the nanoparticle portion of the aerosol compared to the reference (Rnano) was calculated to determine the ability of pDB+CPC with inversion spreadsheet to measure the nanoparticle portion of the aerosols. The Rnano ranged from 0.87 to 1.01 when the inversion solved and from 0.06 to 2.01 when the inversion solved to a constraint. The pDB combined with CPC has limited use as a personal monitor but combining the pDB with a different detector would allow for the pDB to be used as a personal monitor. PMID- 26900208 TI - A Granular Bed for Use in a Nanoparticle Respiratory Deposition Sampler. AB - A granular bed was designed to collect nanoparticles as an alternative to nylon mesh screens for use in a nanoparticle respiratory deposition (NRD) sampler. The granular bed consisted of five layers in series: a coarse mesh, a large-bead layer, a small-bead layer, a second large-bead layer, and a second coarse mesh. The bed was designed to primarily collect particles in the small-bead layer, with the coarse mesh and large-bead layers designed to hold the collection layer in position. The collection efficiency of the granular bed was measured for varying depths of the small-bead layer and for test particles with different shape (cuboid, salt particles; and fractal, and stainless steel and welding particles). Experimental measurements of collection efficiency were compared to estimates of efficiency from theory and to the nanoparticulate matter (NPM) criterion, which was established to reflect the total deposition in the human respiratory system for particles smaller than 300 nm. The shape of the collection efficiency curve for the granular bed was similar to the NPM criterion in these experiments. The collection efficiency increased with increasing depth of the small-bead layer: the particle size associated with 50% collection efficiency, d50, for salt particles was 25 nm for a depth of 2.2 mm, 35 nm for 3.2 mm, and 45 nm for 4.3 mm. The best-fit to the NPM criterion was found for the bed with a small-bead layer of 3.2 mm. Compared to cubic salt particles, the collection efficiency was higher for fractal-shaped particles larger than 50 nm, presumably due to increased interception. PMID- 26900209 TI - The Replacement Rate: An Imperfect Indicator of Pension Adequacy in Cross-Country Analyses. AB - Pension systems are usually evaluated from the perspective of two basic criteria: pension adequacy and financial sustainability. The first criterion concerns the level of pension benefits and protection of the elderly from poverty. The second criterion applies to financial liquidity. This paper is primarily of methodological nature. We discuss the problem of measuring pension adequacy, focusing mainly on the replacement rate, which, defined in a number of ways, is the most common measure of pension adequacy. However, as we argue in this paper, it covers only one of its dimensions, namely consumption smoothing. Meanwhile, an equally important dimension, often discussed in the literature and included in most definitions of pension adequacy, is protection of old-age pensioners from poverty. Accordingly, we have proved the thesis that the replacement rate is not a sufficient measure of broadly understood pension adequacy in cross-country studies. Consequently, we have proposed alternative (or possibly complementary) measures called the synthetic pension adequacy indicators (SPAI1-3), defined in basic form as a quotient of relative median income and the at-risk-of-poverty rate. These indicators provide for both the above-mentioned dimensions of adequacy and, according to statistical analysis, also represent them very well. Moreover, the indicators, calculated separately for men and for women, enables evaluation of the third dimension of pension adequacy, namely gender-related differences in pension adequacy. PMID- 26900210 TI - Conversion of Verbal Response Scales: Robustness Across Demographic Categories. AB - Happiness and life satisfaction have traditionally been measured using verbal response scales, however, these verbal scales have not kept up with the present trend to use numerical response scales. A switch from a verbal scale to a numerical scale, however, causes a severe problem for trend analyses, due to the incomparability of the old and new measurements. The Reference Distribution Method is a method that has been developed recently to deal with this comparison problem. In this method use is made of a reference distribution based on responses to a numerical scale which is used to decide at which point verbally labelled response options transit from one state to another, for example from 'happy' to 'very happy'. Next, for each wave of the time series in which the verbal scale is used, a population mean is estimated for the beta distribution that fits best to these transition points and the responses in this wave. These estimates are on a level that is comparable to that of the mean of the reference distribution and are appropriate for use in an extended time series based on the responses measured using a verbal and a numerical scale. In this paper we address the question of whether the transition points derived for the general population can be used for demographic categories to produce reliable, extended time series to monitor differences in trends among these categories. We conclude that this is possible and that it is not necessary to derive transition points for each demographic category separately. PMID- 26900211 TI - Sex and friendship in a multilevel society: behavioural patterns and associations between female and male Guinea baboons. AB - One key question in social evolution is the identification of factors that promote the formation and maintenance of stable bonds between females and males beyond the mating context. Baboons lend themselves to examine this question, as they vary in social organisation and male-female association patterns. We report the results from the first systematic observations of individually identified wild female Guinea baboons. Guinea baboons live in a multilevel society with female-biased dispersal. Although several males could be found within 5 m of females, each female chiefly associated with one "primary" male at the 2 m distance. Social interactions occurred predominantly with the primary male, and female reproductive state had little influence on interaction patterns. The number of females per primary male varied from 1 to 4. During the 17-month study period, half of the females transferred between different males one or multiple times. A subset of females maintained weaker affiliative nonsexual relationships with other "secondary" males. Units composed of primary males with females, and occasional secondary males, apparently form the core of the Guinea baboon society. The social organisation and mating patterns of Guinea and hamadryas baboons may have a common evolutionary origin, despite notable differences in relationship quality. Specifically, Guinea baboon females appear to have greater leverage in their association patterns than hamadryas baboon females. Although we cannot yet explain the lack of overt male control over females, results generally support the notion that phylogenetic descent may play an important role in shaping social systems. PMID- 26900212 TI - The reproductive advantages of a long life: longevity and senescence in wild female African elephants. AB - Long-lived species such as elephants, whales and primates exhibit extended post fertile survival compared to species with shorter lifespans but data on age related fecundity and survival are limited to few species or populations. We assess relationships between longevity, reproductive onset, reproductive rate and age for 834 longitudinally monitored wild female African elephants in Amboseli, Kenya. The mean known age at first reproduction was 13.8 years; only 5 % commenced reproduction by 10 years. Early reproducers (<12.5 years) had higher age-specific fertility rates than did females who commenced reproduction late (15+ years) with no differences in survival between these groups. Age-specific reproductive rates of females dying before 40 years were reduced by comparison to same-aged survivors, illustrating a mortality filter and reproductive advantages of a long life. Overall, 95 % of fertility was completed before 50, and 95 % of mortality experienced by age 65, with a mean life expectancy of 41 years for females who survived to the minimum age at first birth (9 years). Elephant females have a relatively long period (c. 16 years) of viability after 95 % completed fertility, although reproduction does not entirely cease until they are over 65. We found no evidence of increased investment among females aged over 40 in terms of delay to next birth or calf mortality. The presence of a mother reproducing simultaneously with her daughter was associated with higher rates of daughter reproduction suggesting advantages from maternal (and grandmaternal) co residence during reproduction. PMID- 26900214 TI - Glaucoma: The 'Black hole' of irreversible blindness. PMID- 26900213 TI - Spatial patterns of extra-pair paternity in a waterbird colony: separating the effects of nesting density and nest site location. AB - Centres of avian colonies are usually associated with reduced predation risk and, thus, attract individuals of high quality, while poor-quality individuals are relegated to peripheral zones. Assuming that the incidence of extra-pair paternity (EPP) is dependent on individual quality, we could expect lower incidence of extra-pair offspring in the central parts of colonies. On the other hand, central pairs often nest in higher densities, which might increase EPP rate. To test these hypotheses, we sampled 124 great cormorant Phalacarocorax carbo sinensis chicks from 30 broods from different zones of a colony and genotyped them at seven highly polymorphic microsatellite loci. Sibship reconstruction confirmed the presence of at least one extra-pair chick in 30.0 % of broods. We found that EPP varied significantly between the zones of the colony, with higher incidence of extra-pair broods in the peripheral zone (53.3 vs. 6.7 % of broods). Centre-edge difference in EPP was consistent with the expected distribution of pair quality and suggested that poor-quality peripheral females were more likely to solicit extra-pair interactions, possibly to gain 'good genes' for their offspring. By contrast, we found no evidence for density dependence in EPP rate, indicating that likelihood of raising extra-pair offspring was not constrained by limited availability of local males. The results indicate that spatial randomization of sampling within avian colonies is critical to obtain robust estimations of EPP for non-solitary species. To our knowledge, this study provides the first evidence for the centre-edge difference in EPP within a breeding colony of birds. PMID- 26900215 TI - Paramedical personnel of the Armed Forces Medical Services: The unsung heroes. PMID- 26900216 TI - Acceptance of family planning methods by induced abortion seekers: An observational study over five years. AB - BACKGROUND: Prior to legalization of abortion, induced abortions were performed in an illegal manner and that resulted in many complications hence abortion was legalized in India in 1971 and the number of induced abortions has been gradually increasing since then. One way of preventing abortions is to provide family planning services to these abortion seekers so that same is not repeated. The study was performed to find out the acceptance of contraception after abortion. METHODS: A prospective study was performed over a period of five years from 2010 to 2014. The study group included all the cases reporting for abortion. A proforma was filled in detail to find out the type of contraception being used before pregnancy and acceptance of contraception after abortion. The existing facilities were also evaluated. RESULTS: 1228 abortions were performed over a period of five years. 94.5% of abortions were during the first trimester. 39.9% had not used any contraceptive before, contraceptives used were natural and barrier which had high failure. The main indication for seeking abortion was failure of contraception and completion of family. 39.6% of patients accepted sterilization as a method of contraception. The existing post abortion family planning services are inadequate. CONCLUSION: Post abortion period is one which is important to prevent subsequent abortions and family planning services after abortion need to be strengthened. PMID- 26900217 TI - Evaluation of surgical outcomes following oncoplastic breast surgery in early breast cancer and comparison with conventional breast conservation surgery. AB - BACKGROUND: The aim of this study was to determine whether oncoplastic breast surgery (OBS) ensures better tumour resection than conventional breast conservation surgery (BCS). METHODS: A prospective comparative study, conducted over a 3-year period, enrolled patients with early breast cancer who underwent OBS. The total volume of glandular resection, tumour volume resection and width of the margins obtained were noted. The incidence of complications, requirement of revision surgery and locoregional recurrence during follow-up period were also noted. The data were compared with matched controls who had undergone convention BCS in the past. RESULTS: Thirty-three patients underwent oncoplastic surgery and the data was compared with 46 patients of conventional breast conservation. The mean volume of specimen was higher in the oncoplastic group (173.5 cm(3) vs 101.4 cm(3), p = 0.03) though the tumour volume excised was similar (43.2 cm(3) vs 36.4 cm(3), p = 0.14). The mean margin widths were larger in the oncoplastic group (14 mm vs 6 mm, p = 0.01). There were more instances of close and positive margins seen in conventional BCS groups. The incidence of complication rate was similar. Median follow-up 18 months for oncoplasty group showed no cases of locoregional recurrence while in median follow-up of 38 months for conventional BCS group, six cases of locoregional relapse were noted. CONCLUSIONS: Oncoplastic surgery results in excision of larger volume of breast tissue and correspondingly obtain wider surgical margins as compared to conventional BCS. Longer follow-up is required to determine if wider resection translates into better locoregional control. PMID- 26900218 TI - To study the effects of gamma irradiation on single donor apheresis platelet units by measurement of cellular counts, functional indicators and a panel of biochemical parameters, in order to assess pre-transfusion platelet quantity and quality during the shelf life of the product. AB - BACKGROUND: The occurrence of transfusion associated graft versus host disease can be prevented by gamma irradiation of blood components. This study was undertaken to assess the effects of gamma irradiation on single donor platelet (SDP) concentrate units. METHOD: SDPs were collected by a continuous flow apheresis technique (n = 400). The SDPs from each donor were divided into two parts, one gamma-irradiated with 25 Gy and the other used as a non-irradiated control. Swirling and morphological features, cellular counts, biochemical parameters including blood gas analysis, and platelet activation levels (CD62P: p selectin) by flow cytometry were analyzed on Day 1 and on Day 5. RESULTS: Swirling and morphology were maintained in all products, in both the groups throughout the shelf life. No significant change was seen in both groups, on the first and fifth day, as far as pO2, pCO2, Na(+), K(+), HCO3 (-) & Ca(2+) were concerned. However, lactate increased and glucose decreased significantly in irradiated products over 5-day storage period. A small but significant decrease in pH and platelet count was found in the irradiated PCs after 5-day storage. The mean proportion of platelets expressing CD62P over 5-day storage increased significantly. CONCLUSION: After an overall assessment of all our in vitro parameter results and observations, a few of which were significant, while most were not significant, we concluded that a well-preserved quality of gamma irradiated apheresis platelets is maintained throughout the entire 5-day shelf life of the platelet product, with minimal difference compared to non-irradiated platelets. PMID- 26900219 TI - Study of a structured action pathway and persistent monitoring tool among nurses to achieve cent percent management of hypoglycaemia in in-patients: A measure of quality of healthcare. AB - BACKGROUND: Reporting and management of hypoglycaemia is a reflection of quality of healthcare delivery. The study evaluates success of a structured plan implemented in a tertiary care hospital in terms of an evidence-based hypoglycaemia management protocol, training and awareness among all nurses in the organisation to achieve 100% reporting of hypoglycaemia. METHODS: A prospective study was conducted over a 3-year period. An in-house hypoglycaemia management protocol was designed, included in the induction training programme of nurses and implemented in wards under the guidance of master trainers. Each episode of hypoglycaemia was reported, managed and logged into centralised database, Quality Flash Matrix (QF). The QF was analysed at end of each 24 h cycle to carry out a root cause analyses and appropriate correction in training modules. Data were extracted from hospital records, patient case records and QF in terms of total number of cases receiving insulin and total number of episodes of hypoglycaemia documented and reported. RESULTS: Incidence of hypoglycaemia recorded was 6.4, 5.3 and 4.7 per 1000 patient hours for the years 2011, 2012 and 2013, respectively. The percentage of episodes of hypoglycaemia reported improved from 78% (1st quarter 2011) to 100% (4th quarter 2012). Root cause analysis showed change in diet of patient with no corresponding change in insulin and vice versa being the commonest cause for hypoglycaemia consistent over the study period. CONCLUSION: Constant structured training of nurses, constant surveillance and appropriate feedback analysis result in decreased incidence of hypoglycaemia and increased reporting of episodes of hypoglycaemia. PMID- 26900220 TI - 'Empty sella' on routine MRI studies: An incidental finding or otherwise? AB - BACKGROUND: Empty sella (ES) has been regarded as an incidental finding. Recently, there have been studies documenting association of ES with hormonal and non-hormonal abnormalities. To detect the prevalence of empty sella in routine MRI brain study and to find associations with other diseases. METHODS: A retrospective study was carried out for patients undergoing MRI brain studies in the radiology department of a teaching institution. Patients with ES formed the study group. The rest formed the baseline population. Presence of nine select variables, viz. hormonal disturbances, headache, sensorineural hearing loss, seizures, vertigo, psychiatric disorders, visual disturbances, ataxia and raised intracranial tension, was analyzed amongst the study group, as well as the baseline population. Association of ES and the select variables was analyzed by determining means and proportions and using Chi-square test. RESULTS: During the study period, a total of 12,414 patients underwent MRI brain studies at our centre. ES was found in 241 (1.94%) patients. The proportion of patients in the ES and non-empty sella groups for each of the variables were as follows: hormonal disturbances (3.31% vs 0.56%, P = .000), headache (8.3% vs 7.4%, P = .596), SNHL (3.7% vs 1.3%, P = .0010), seizure (6.2% vs 13%, P = .002), vertigo (4.6% vs 1.6%, P = .000), psychiatric disorders (4.6% vs 1.3%, P = .000), visual disturbances (2% vs 1.1%, P = .166), ataxia (1.7% vs 1.2%, P = .519) and raised ICT (2% vs 0.5%, P = .002). CONCLUSION: Hormonal disturbances, psychiatric disorders, raised ICT and SNHL have been found to be more often associated with ES as compared to general population. PMID- 26900221 TI - Blood lactate changes in professional Indian divers under hyperbaric conditions. AB - BACKGROUND: Hyperoxia due to hyperbaric conditions influences lactate metabolism. Previous studies on lactate levels in hyperbaric conditions have reported varied results depending on the depth of evaluation and breathing gas mixture used. METHODS: This study compared post-exercise blood lactate levels of Indian professional male divers (breathing ambient air under normobaric conditions) with their post-exercise blood lactate levels measured under simulated hyperbaric conditions. RESULT: In the present study, blood lactate levels in divers were found to have decreased significantly during recovery phase of exercise in hyperbaric conditions of dry diving at 2.8 Atmospheres Absolute (ATA) as compared to normobaric conditions. A significant improvement was observed in physical performance in terms of HR max and duration of exercise. CONCLUSION: This study revealed that hyperoxia due to moderate hyperbaric condition leads to improvement in lactate metabolism in muscles and organs (liver and heart) for its removal. PMID- 26900222 TI - Spectrum of ocular diseases in patients attending eye camps in Andaman and Nicobar. AB - BACKGROUND: Andaman and Nicobar Island is a group of 572 islands with a population of 3,80,500. The only service hospital as well as govt hospital is situated at its capital, Portblair. The islands are interconnected only by sea passage and to reach the capital by this route it sometimes takes two days. METHODS: The objective of this study is to assess the spectrum of different ocular diseases in remote islands of Andaman and Nicobar. Author had conducted various camps on these remote islands as a community outreach programme over two years. RESULTS: Top eye diseases found were refractive error (35%), cataract (22%), conjunctival infammatory disease (15%), glaucoma cases (07%), pterygium (07%), NLDO (02%) and uveitis (02%). Out of total 132 cataract patients screened, 32 patients (approximately 24%) were operated in INHS Dhanvantari at free of cost with help of NPCB (National Programme for Control of Blindness). CONCLUSION: This was the first kind of study conducted on these remote islands to know the prevalence of different ocular diseases. The important point to be seen in this study was unawareness of glaucoma and cataract load. No optometrist was posted in the PHCs to provide primary eye care like prescribing glasses, which is also a big concern. PMID- 26900223 TI - Role of single photon emission computerised tomography in evaluating osseointegration of indigenous DRDO implants: An in vivo study. AB - BACKGROUND: A study of first indigenous titanium dental implant developed by DRDO was undertaken at INMAS, Delhi. The aim was to establish the time taken for osseointegration, along with objectives to define the time of implant loading and compare the osseointegration of indigenous dental implants with already established dental implant systems. METHODS: 21 subjects rehabilitated using 39 indigenous dental implants were evaluated by bone SPECT before implantation and at regular intervals towards establishing the aim and objectives. RESULTS: The rise followed by fall in Osteoblastic activity indicates the postoperative physiologic changes, which peaked at 2 weeks (mean) post-implantation and falls off to pre-implantation levels in 12 weeks (mean) indicating completion of osseointegration, healing and time of loading. CONCLUSION: It can be summarized that the Osteoblastic activity of indigenous dental implants completes within three months, which can be taken as the time required for complete healing/osseointegration and loading the implants. On comparison with the available data of already established implants the figures appear similar, indicating indigenous implants to be similar in biologic behaviour. PMID- 26900224 TI - Antiretroviral therapy: Shifting sands. AB - HIV/AIDS has been an extremely difficult pandemic to control. However, with the advent of antiretroviral therapy (ART), HIV has now been transformed into a chronic illness in patients who have continued treatment access and excellent long-term adherence. Existing indications for ART initiation in asymptomatic patients were based on CD4 levels; however, recent evidence has broken the shackles of CD4 levels. Early initiation of ART in HIV patients irrespective of CD4 counts can have profound positive impact on morbidity and mortality. Early initiation of ART has been found not only beneficial for patients but also to community as it reduces the risk of transmission. There have been few financial concerns about providing ART to all HIV-positive people but various studies have proven that early initiation of ART not only proves to be cost-effective but also contributes to economic and social growth of community. A novel multidisciplinary approach with early initiation and availability of ART at its heart can turn the tide in our favor in future. Effective preexposure prophylaxis and postexposure prophylaxis can also lower transmission risk of HIV in community. New understanding of HIV pathogenesis is opening new vistas to cure and prevention. Various promising candidate vaccines and drugs are undergoing aggressive clinical trials, raising optimism for an ever-elusive cure for HIV. This review describes various facets of tectonic shift in management of HIV. PMID- 26900225 TI - Improving medical stores management through automation and effective communication. AB - BACKGROUND: Medical stores management in hospitals is a tedious and time consuming chore with limited resources tasked for the purpose and poor penetration of Information Technology. The process of automation is slow paced due to various inherent factors and is being challenged by the increasing inventory loads and escalating budgets for procurement of drugs. METHODS: We carried out an indepth case study at the Medical Stores of a tertiary care health care facility. An iterative six step Quality Improvement (QI) process was implemented based on the Plan-Do-Study-Act (PDSA) cycle. The QI process was modified as per requirement to fit the medical stores management model. The results were evaluated after six months. RESULTS: After the implementation of QI process, 55 drugs of the medical store inventory which had expired since 2009 onwards were replaced with fresh stock by the suppliers as a result of effective communication through upgraded database management. Various pending audit objections were dropped due to the streamlined documentation and processes. Inventory management improved drastically due to automation, with disposal orders being initiated four months prior to the expiry of drugs and correct demands being generated two months prior to depletion of stocks. The monthly expense summary of drugs was now being done within ten days of the closing month. CONCLUSION: Improving communication systems within the hospital with vendor database management and reaching out to clinicians is important. Automation of inventory management requires to be simple and user-friendly, utilizing existing hardware. Physical stores monitoring is indispensable, especially due to the scattered nature of stores. Staff training and standardized documentation protocols are the other keystones for optimal medical store management. PMID- 26900226 TI - Nevus Lipomatosis Cutaneous Superficialis - A clinicopathologic study of the solitary type. AB - BACKGROUND: Nevus Lipomatosis Cutaneous Superficialis (NLCS) is a rare, benign hamartomatous lesion characterized by the ectopic presence of mature adipocytes in the reticular dermis not associated with the underlying subcutaneous tissue. Two clinical forms-classical and solitary occur. The solitary form is relatively uncommon, due to which these lesions are commonly clinically misdiagnosed. The aim was to study the clinical and histopathological features of the solitary type of NLCS. METHODS: Seven cases of histopathologically documented solitary type of NLCS which presented at our institute between August 2013 and June 2014 were retrospectively analysed for clinical data and histopathological findings. Haematoxylin and Eosin (H&E) and Elastic Van Gieson (EVG) stained slides were studied in all cases. RESULTS: Mean age of the patients was 42.5 years. These lesions were more common in adult females (5/7). Thigh was the commonest location (4/7). The mean duration of these lesions was 2.0 years. Clinical diagnosis was papilloma (4/7) and acrochordon (3/7). Histopathology revealed the presence of varying amounts of mature ectopic adipocytes in the dermis located around dilated, ectactic blood vessels. Disorganised dermal collagen bundles and atrophic pilosebaceous units were seen. CONCLUSION: This study is a first from the Indian subcontinent and highlights the need for awareness of this rare clinical condition both by the dermatologists and the surgeons. Histopathology is essential for diagnosis as clinically they may mimic papillomas or skin tags. An early diagnosis may permit a more conservative resection of the tumour. PMID- 26900227 TI - Species distribution and antimicrobial resistance pattern of Coagulase-negative Staphylococci at a tertiary care centre. AB - BACKGROUND: Coagulase-negative Staphylococci (CoNS), previously dismissed at contaminants, have now emerged as an important cause of nosocomial infections especially in patients with implants and prosthetic devices. They are a well known cause of bloodstream infections, urinary tract infections, wound infections, prosthetic valve endocarditis and eye infections. This study was conducted with an aim to identify CoNS at the species level from various clinical samples and determine the antimicrobial resistance pattern of these isolates. METHODS: This cross sectional study was carried out from September 2011 to February 2014 in which 150 non-repetitive clinical isolates of CoNS were identified at the species level by conventional phenotypic methods. Complete antimicrobial susceptibility profile was also determined by Kirby Bauer disc diffusion method. Susceptibility testing to vancomycin was done by E-test method. RESULTS: Only three species of CoNS were isolated, the most common being Staphylococcusepidermidis (60%) followed by Staphylococcussaprophyticus (27.3%) and Staphylococcushemolyticus (12.7%). Most S. epidermidis were isolated from blood and intravascular catheter tip samples, whereas all S. saprophyticus were isolated from urine samples of female patients. All isolates were found to be resistant to penicillin, but were susceptible to glycopeptides and linezolid and showed variable resistance to fluoroquinolones, aminoglycosides and macrolides. CONCLUSION: CoNS are emerging nosocomial pathogens and should not always be overlooked as contaminants. However, growth of CoNS from blood cultures and intravascular catheter tips should be clinically correlated and carefully interpreted. As many CoNS strains exhibit drug resistance, antimicrobial susceptibility profile should be determined prior to treatment of these infections. PMID- 26900228 TI - Hypoxic-Ischemic brain injury in an adult: Magnetic Resonance Imaging findings. PMID- 26900229 TI - Ultrasonography and magnetic resonance imaging of ulnar nerve abscess in leprosy. PMID- 26900230 TI - A case of orbitocranial foreign body. PMID- 26900231 TI - Intraosseous hemangioma of the zygomatic bone: A rare site for hemangioma. PMID- 26900232 TI - A case of Aspergillus nidulans causing white granule mycetoma. PMID- 26900233 TI - Primary amyloidosis of urinary bladder: Mimicking transitional cell carcinoma bladder? PMID- 26900234 TI - Missed retained tick: "Look for the legs". PMID- 26900235 TI - Letter to the Editor. PMID- 26900236 TI - Reply. PMID- 26900237 TI - Cutaneous pili migrans: A creeping eruption like condition easy to diagnose and cure. PMID- 26900238 TI - Interpretation of ER and Her2neu hormonal receptor in breast cancer. PMID- 26900239 TI - Aspiration of endodontic file. PMID- 26900240 TI - Reply. PMID- 26900241 TI - Evaluation of three-dimensional mandibular movements after reconstruction with free fibula flap. AB - Seven patients who underwent mandibular reconstruction with a fibula free flap (one on the midline, six on either right or left side) and were rehabilitated with implant supported prostheses, performed free mandibular border movements (maximal mouth opening and closing, right and left lateral excursions, protrusion) that were recorded by a non-invasive motion analyser. Temporomandibular joint (TMJ) kinematic parameters were compared to those calculated in healthy control subjects using z-scores. Maximum mouth opening was reduced in all patients, with z-scores ranging from -2.742 to -0.106, and performed with a reduced sagittal plane mandibular rotation. Interincisal point forward movement during protrusion was reduced in all but one patient. Lateral mandibular movements (displacement of the interincisal point) and bilateral condylar movements during mouth opening were very variable and sometimes asymmetrical. Mandibular rotation was also variable, with z-scores ranging from 1.265 to 1.388. Together with mandibular range of motion, we investigated biomechanical characteristics of TMJ motion that can provide further information about the joint without submitting the patient to harmful procedures, and that can be followed-up during healing. The investigation indicates those areas that need to be given special attention in preoperative planning, patient information and rehabilitation. PMID- 26900242 TI - Human papillomavirus-associated cancers: a survey on otorhinolaryngologists' knowledge and attitudes on prevention. AB - Human papillomavirus (HPV) infection is a recognised causal factor associated with oropharyngeal cancers. The global burden of HPVrelated oropharyngeal cancers is on the increase and is predicted to surpass the burden of cervical cancer in the near future. As evidence is accumulating on the potential effectiveness of an HPV vaccine in controlling the oropharyngeal cancer epidemic; otorhinolaryngologists assume a key role - not only in the diagnosis and treatment of HPV-related cancers - but also in educating and advocating on HPV prevention. We conducted a survey to assess Italian otorhinolaryngologists' knowledge and attitudes regarding HPV infection, HPV-related oropharyngeal diseases and cancers and available prevention measures, including vaccines. This is the first study conducted in Italy and Europe on this topic. A total of 262 Italian otorhinolaryngologists were recruited during the National Conference of the Italian Association of Otorhinolaryngologists. Our results show that Italian otorhinolaryngologists are knowledgeable regarding HPV infection and have a positive attitude towards HPV vaccine. Our findings provide a useful basis to plan, implement and evaluate targeted educational programmes and training. As we show herein, educational programmes and training specifically focusing on HPV are effective in increasing physicians' knowledge and positive attitudes towards prevention; this ultimately contributes to enhance vaccine uptake among patients and the general population. With the overall aim of controlling the burden of HPV related cancers, resources and efforts should be devoted to promote continuing education among otorhinolaryngologists and the general medical community and to increase awareness on the role of vaccines in prevention of HPV-related cancers. In this context, there is tremendous opportunity for healthcare providers across fields to cooperate and for public health and otorhinolaryngologist communities to join forces and engage in fruitful collaboration. PMID- 26900243 TI - Impact of microvascular free flap reconstruction in oral cavity cancer: our experience in 130 cases. AB - The aim of this study was to investigate the oncological outcomes in patients affected by oral carcinoma treated with radical compartmental surgery followed by microvascular flap reconstruction. We conducted a retrospective analysis on a cohort of 130 patients. All patients underwent ablative tumour resection (compartmental surgery) followed by immediate reconstruction with free flaps and adjuvant chemoradiotherapy, when necessary according to our tumour board and international guidelines. Disease-specific survival (DSS) curves were obtained using the Kaplan-Meier method. Log-rank test and generalised Wilcoxon test were used to investigate the most important prognostic factors on 5-year DSS. A Cox proportional hazards model was constructed to provide hazard ratios or relative risks for individual variables. 88.5% of patients were affected by SCC. There were 46 (35.4%) women and 84 (64.6%) men in the sample with a mean age of 58.5 years. At the end of the follow-up period, 36 (27.7%) patients died, only 3 of which for other causes. The 5-year DSS rate was 67.8% (S.E. 4.9%). In univariate Kaplan-Meier analysis and in multivariate Cox regression model, seven variables were found to have a significant relationship with DSS: T (p = 0.026) and N (p = 0.0001) status, clinical stage (according to the UICC TNM Sixth Edition) (p = 0.007), margins of resection (p = 0.001), extracapsular spread (p = 0.005), recurrence of disease (p = 0.00002) and treatment modality (evaluated as surgery alone or surgery + RT/CHT) (p = 0.004). Our results confirmed findings already reported in the literature, and allowed us to conclude that compartmental surgery combined with free flap reconstruction can increase survival in oral cancer patients. PMID- 26900244 TI - Osteoperiosteal free fibula flap as an effective preprosthetic reconstructive option in severe jaw atrophy and oncological resection. AB - The gold standard in modern surgical treatment of patients with severe maxillo mandibular atrophy must include the aim to achieve restoration of function and aesthetics with immediate reconstruction of the oro-mandibular defects. The medical records of 14 patients who were treated in a 5-year period (2010-2014) at our department with severe maxillary and mandibular atrophy, and reconstructed by vascularised free fibula flap were reviewed. Among the former, a total of 14 patients underwent maxillary and mandibular reconstruction using the osteoperiosteal fibula free flap. No major complications were reported. The main advantage of this technique is that it allows the formation of keratinised gengiva, which provides the best implantological options. The only disadvantage of the technique is that the wounds have to heal for second intention, and for this reason patients have to undergo strict follow-up for the first months after the operation. The aim of this article is to evaluate the efficiency of the technique in bone reconstruction after jaw resection or severe atrophy. PMID- 26900245 TI - Pharyngocutaneous fistula following total laryngectomy: analysis of risk factors, prognosis and treatment modalities. AB - The aim of this study was to establish the incidence, risk factors, and the management of pharyngocutaneous fistula (PCF) after primary and salvage total laryngectomy. A retrospective, match-paired analysis of 86 patients who developed fistula after total laryngectomy was carried out and compared with a control group of 86 patients without fistula, randomly selected from a pool of 352 total laryngectomies, performed between January 1999 to October 2014. The overall incidence of PCF in the series was 24.4%; we recorded rates of 19.0%, 28.6% and 30.3% following primary total laryngectomy (PTL), salvage laryngectomy post radiotherapy (RT-STL) and salvage laryngectomy postchemoradiotherapy (CRT-STL), respectively. Multivariate analysis revealed that the relative risk of fistula was respectively 2.47, 3.09 and 7.69 for hypoalbuminaemia <=3.5 g/dL, RT-STL and CRT-STL. An early onset of PCF within 10 postoperative days was recorded in case of salvage total laryngectomy. The management of PCF significantly differed between PTL, RT-STL and CTRT-STL, with exclusive conservative treatment for PTL (93.55%), while in the CRT-STL group surgical closure with regional flaps (58.82%) prevailed. Conservative management, adjuvant hyperbaric oxygen therapy and surgical closure were equally distributed in the RT-STL group. Thorough knowledge of patient-related risk factors and its prognostic value, allows the surgeon to better evaluate preventive strategies with the aim of minimising fistula formation, hospitalisation times and related costs. PMID- 26900246 TI - Use of the SMAS flap for reconstruction of the parotid lodge. AB - The purpose of our study was to evaluate the benefits of the SMAS flap in patients with benign tumours of the parotid gland treated by superficial parotidectomy. We carried out a retrospective chart review on 123 patients suffering from benign tumours of the parotid gland admitted to our Institution between March 1997 and March 2010. A superficial parotidectomy was performed in all the cases reported. Our sample was divided in two groups basing SMAS flap reconstruction done (Group 2) or not (Group 1) after superficial parotidectomy. Reconstruction using SMAS flap was accomplished in 64 patients. Chi-square test was used to assess statistical difference between the two groups. The level of statistical significance was P < 0.05. No significant differences concerning hematoma, wound infection and facial paralysis were observed between the first and second group (3.38 vs 1.56% [P > 0.05], 8.47% vs 4.68% [P > 0.05], 5.08% vs 0.00% [P > 0.05]). Transient facial nerve weakness, fistula, dip skin and Frey's syndrome were significantly more frequent without SMAS flap reconstruction (10.16% vs 3.125% [P < 0.05], 13.55% vs 3.125% [P < 0.05], 13.55% vs 3.125% [P < 0.05], 20.33% vs 0% [P < 0.05] respectively). The use of the SMAS flap is able to reduce the cosmetic and functional complications that occur after the removal of a benign tumour of the parotid through the superficial parotidectomy technique, above all, it reduces the occurrence of Frey's syndrome. PMID- 26900247 TI - Post-laryngectomy voice rehabilitation with voice prosthesis: 15 years experience of the ENT Clinic of University of Catania. Retrospective data analysis and literature review. AB - This study reports our 15-year experience, in Sicily, with the use of voice prostheses, analysing the different variables that have influenced the success or failure of speech rehabilitation. The retrospective clinical analysis was carried out by reviewing the clinical histories of 95 patients with laryngeal cancer, in whom a voice prosthesis had been placed by trachea-oesophageal puncture between 1998 and 2013. Age, type of tumour, type of surgery, use of prior radiation therapy, type of puncture, prosthesis used and its duration, number of replacements, complications and causes for prosthetic success or failure were analysed. The results showed a mean of Harrison-Robillard-Schultz (HRS) TEP rating scale of 11.8 in primary TEP and 12.6 in secondary TEP (P =0.613). PORT did not affect overall rehabilitation success. In these patients, the mean HRS rating scale was 11.2, with long-term success of 85% (P =0.582). In patients over 70 years old, long-term success was 82.5%, with 78% in primary and 86% in secondary TEP, the mean HRS was 11.2 in primary and 12 in secondary TEP (P =0.648). In total, long-term success was 87.5%, with 84% in primary and 91% in secondary TEP. The results obtained by retrospective analysis of 15 years of prosthetic rehabilitation in the Sicilian territory highlighted standard rehabilitation, in terms of intra and postoperative complications, fistula related pathology and overall success. PMID- 26900248 TI - Oxidative stress in patients with obstructive sleep apnoea syndrome. AB - Obstructive sleep apnoea syndrome (OSAS) is a disorder that leads to metabolic abnormalities and increased cardiovascular risk. The aim of this study was to identify early laboratory markers of cardiovascular disease through analysis of oxidative stress in normal subjects and patients with OSAS. A prospective study was designed to compare outcomes of oxidative stress laboratory tests in 20 adult patients with OSAS and a control group of 20 normal subjects. Laboratory techniques for detecting and quantifying free radical damage must be targeted to assess the pro-oxidant component and the antioxidant in order to obtain an overall picture of oxidative balance. No statistical differences in age, sex distribution, or BMI were found between the two groups (p>0.05). There were significant differences in the apnoea/hypopnoea index (AHI) between OSAS patients and the control group (p<0.05). Statistically significant differences in isoprostane, advanced oxidation protein products (AOPP) and non-protein bound iron (NPBI) levels were found between the study and control groups. No significant difference in the levels of thiol biomarkers was found between the two groups. The main finding of the present study was increased production of oxidative stress biomarkers in OSAS patients. The major difference between thiols and other oxidative stress biomarkers is that thiols are antioxidants, while the others are expressions of oxidative damage. The findings of the present study indicate that biomarkers of oxidative stress in OSAS may be used as a marker of upper airway obstructive episodes due to mechanical trauma, as well as a marker of hypoxaemia causing local oropharyngeal inflammation. PMID- 26900249 TI - Drug-induced sleep endoscopy as a selection tool for mandibular advancement therapy by oral device in patients with mild to moderate obstructive sleep apnoea. AB - Nowadays oral appliance therapy is recognised as an effective therapy for many patients with primary snoring and mild to moderate obstructive sleep apnoea (OSA), as well as those with more severe OSA who cannot tolerate positive airway pressure (PAP) therapies. For this reason, it is important to focus on objective criteria to indicate which subjects may benefit from treatment with a mandibular advancement device (MAD). Various anthropometric and polysomnographic predictors have been described in the literature, whereas there are still controversies about the role of drug-induced sleep endoscopy (DISE) and advancement bimanual manoeuvre as predictor factors of treatment outcome by oral device. Herein, we report our experience in treatment of mild moderate OSA by oral appliance selected by DISE. We performed a single institution, longitudinal prospective evaluation of a consecutive group of mild moderate patients with obstructive sleep apnoea syndrome who underwent DISE. During sleep endoscopy, gentle manoeuvre of mandibular advancement less than 5 mm was performed. In 30 of 65 patients (46.2%) we obtained an unsuccessful improvement of airway patency whereas in 35 of 65 patients (53.8%) the improvement was successful and patients were considered suitable for oral device application. Because 7 of 35 patients were excluded due to conditions interfering with oral appliance therapy, we finally treated 28 patients. After 3 months of treatment, we observed a significant improvement in the Epworth medium index [(7.35 +/- 2.8 versus 4.1 +/- 2.2 (p < 0.05)], in mean AHI [(21.4 +/- 6 events per hour versus 8.85 +/- 6.9 (p < 0.05)] and in mean ODI [(18.6 +/- 8 events per hour to 7 +/- 5.8 (p < 0.05)]. We observed that the apnoea/hypopnoea index (AHI) improved by up to 50% from baseline in 71.4% of patients selected after DISE for MAD therapy. In the current study, mandibular advancement splint therapy was successfully prescribed on the basis not only of severity of disease, as determined by the subject's initial AHI, but also by DISE findings combined with results of gentle mandibular advancement manoeuvre allowing direct view of the effects of mandibular protrusion on breathing spaces in obstruction sites, and showing good optimisation of selection of patients for oral device treatment. PMID- 26900250 TI - Factors affecting residual hearing preservation in cochlear implantation. AB - The likelihood of residual hearing preservation in cochlear implantation (CI) is related to surgical factors such as type of cochleostomy (trans-fenestral vs. promontorial), use of lubricants and protective drugs, and device-related factors such as shape, length and flexibility of the array. We investigated the impact of these factors on the hearing preservation rate in adults and children with conventional audiological indications to CI. Eighty-two children aged 1-9 years and 73 adults (16-79 years) received a CI in the right (59%) or left ear (41%). An anterior-inferior promontorial cochleostomy was performed in 143 ears (92%); a trans-fenestral approach was used in 12 (8%). A perimodiolar electrode was implanted in 144 ears (93%), and a straight electrode in the remaining 11 (7%). Overall, some post-operative hearing was retained in 39% of ears. The rate of preservation was higher at the low than at the high frequencies. When correlated with age, side of implant, implant model and type of cochleostomy, the mean threshold variations did not reach statistical significance for any of these variables. A slight trend in favour of better residual hearing preservation in children vs. adults was seen, especially at lower frequencies. PMID- 26900251 TI - Role of bimodal stimulation for auditory-perceptual skills development in children with a unilateral cochlear implant. AB - This is a prospective randomised study that evaluated the differences arising from a bimodal stimulation compared to a monaural electrical stimulation in deaf children, particularly in terms of auditory-perceptual skills development. We enrolled 39 children aged 12 to 36 months, suffering from severe-to-profound bilateral sensorineural hearing loss with residual hearing on at least one side. All were unilaterally implanted: 21 wore only the cochlear implant (CI) (unilateral CI group), while the other 18 used the CI and a contralateral hearing aid at the same time (bimodal group). They were assessed with a test battery designed to appraise preverbal and verbal auditory-perceptual skills immediately before and 6 and 12 months after implantation. No statistically significant differences were observed between groups at time 0, while at 6 and 12 months children in the bimodal group had better scores in each test than peers in the unilateral CI group. Therefore, although unilateral deafness/hearing does not undermine hearing acuity in normal listening, the simultaneous use of a CI and a contralateral hearing aid (binaural hearing through a bimodal stimulation) provides an advantage in terms of acquisition of auditory-perceptual skills, allowing children to achieve the basic milestones of auditory perception faster and in greater number than children with only one CI. Thus, "keeping awake" the contralateral auditory pathway, albeit not crucial in determining auditory acuity, guarantees benefits compared with the use of the implant alone. These findings provide initial evidence to establish shared guidelines for better rehabilitation of patients undergoing unilateral cochlear implantation, and add more evidence regarding the correct indications for bilateral cochlear implantation. PMID- 26900252 TI - The GOCCLES(r) medical device is effective in detecting oral cancer and dysplasia in dental clinical setting. Results from a multicentre clinical trial. AB - The purpose of this study is to demonstrate that the GOCCLES(r) medical device allows proper autofluorescence examination of the oral mucosa in a dental care setting. This is a non-randomised multicentre clinical trial on consecutive patients at risk for oral cancer. Patients underwent a classical naked eye inspection of the oral cavity followed by autofluorescence examination wearing the GOCCLES(r) spectacles while the light from a dental curing light irradiated the oral mucosa. Lesions were defined as visible potentially malignant lesions and/or fluorescence loss areas. All persisting lesions underwent excisional or incisional biopsy. Sixty-one patients were enrolled. Data from 64 biopsies were analysed. Of the 62 lesions identified by the device, 31 were true positives. The device identified 31 of 32 true positive lesions. One lesion (an invasive carcinoma) was not visible to the naked eye. The device identified all lesions classified as moderate dysplasia to invasive cancer. In 56.7% of cases, true positive lesions showed greater extension when observed through the device. The GOCCLES(r) medical device allowed the direct visualisation of fluorescence loss in patients suffering from mild to severe dysplasia and in situ to invasive oral cancer. It allowed autofluorescence examination with each source of light used during the study. These results suggest that the role of the autofluorescence visualisation is that of a complementary inspection following naked eye examination when dealing with patients at risk for oral cancer. The device allows detection of otherwise invisible lesions and otherwise impossible complete resections. PMID- 26900253 TI - Sinonasal and rhinopharyngeal solitary fibrous tumour: a case report and review of the literature. AB - Solitary fibrous tumours are rare neoplasms that arise mostly from the pleura. Much more rarely they can also be found in extrapleural sites, including the head and neck. We report a rare case of a sinonasal and rhinopharyngeal solitary fibrous tumour. The tumour, measuring 67 x 28 x 55 mm, was first embolised and then successfully removed through endonasal endoscopic surgery. Histopathologic analysis confirmed the nature of the lesion, which was positive for CD34 and vimentin. A post-operative CT scan and endoscopic follow-up demonstrated total resection and absence of recurrence after 13 months. PMID- 26900254 TI - Orthotic Body-Weight Support Through Underactuated Potential Energy Shaping with Contact Constraints. AB - Body-weight support is an effective clinical tool for gait rehabilitation after neurological impairment. Body-weight supported training systems have been developed to help patients regain mobility and confidence during walking, but conventional systems constrain the patient's treatment in clinical environments. We propose that this challenge could be addressed by virtually providing patients with body-weight support through the actuators of a powered orthosis (or exoskeleton) utilizing potential energy shaping control. However, the changing contact conditions and degrees of underactuation encountered during human walking present significant challenges to consistently matching a desired potential energy for the human in closed loop. We therefore introduce a generalized matching condition for shaping Lagrangian systems with holonomic contact constraints. By satisfying this matching condition for four phases of gait, we derive control laws to achieve virtual body-weight support through a powered knee ankle orthosis. We demonstrate beneficial effects of virtual body-weight support in simulations of a human-like biped model, indicating the potential clinical value of this proposed control approach. PMID- 26900255 TI - Child Care Enrollment Decisions Among Dual Language Learner Families: The Role of Spanish Language Instruction in the Child Care Setting. AB - Data from the Head Start Impact Study (N = 1,141) and the Head Start Family and Child Experiences Survey, 2009 Cohort (N = 825) were used to describe child care enrollment decisions among Spanish-speaking Dual Language Learner (DLL) families. In particular, logistic regression models tested which child, family, and institutional characteristics predicted enrollment in early care and education (ECE) settings that used Spanish for instruction versus enrollment in settings that did not use Spanish. Results showed that whether the child's first language was exclusively Spanish and whether other DLL families previously attended the ECE arrangement strongly predicted whether that child enrolled. Policy implications for Head Start-eligible Spanish-speaking DLLs are discussed. PMID- 26900256 TI - Feasibility of the Simultaneous Determination of Monomer Concentrations and Particle Size in Emulsion Polymerization Using in Situ Raman Spectroscopy. AB - An immersion Raman probe was used in emulsion copolymerization reactions to measure monomer concentrations and particle sizes. Quantitative determination of monomer concentrations is feasible in two-monomer copolymerizations, but only the overall conversion could be measured by Raman spectroscopy in a four-monomer copolymerization. The feasibility of measuring monomer conversion and particle size was established using partial least-squares (PLS) calibration models. A simplified theoretical framework for the measurement of particle sizes based on photon scattering is presented, based on the elastic-sphere-vibration and surface tension models. PMID- 26900257 TI - Is Trait Rumination Associated with the Ability to Generate Effective Problem Solving Strategies? Utilizing Two Versions of the Means-Ends Problem-Solving Test. AB - This study examined the relationship between trait rumination and the effectiveness of problem solving strategies as assessed by the Means-Ends Problem Solving Test (MEPS) in a nonclinical population. The present study extended previous studies in terms of using two instructions in the MEPS: the second person, actual strategy instructions, which has been utilized in previous studies on rumination, and the third-person, ideal-strategy instructions, which is considered more suitable for assessing the effectiveness of problem solving strategies. We also replicated the association between rumination and each dimension of the Social Problem-Solving Inventory-Revised Short Version (SPSI R:S). Japanese undergraduate students (N = 223) completed the Beck Depression Inventory-Second Edition, Ruminative Responses Scale (RRS), MEPS, and SPSI-R:S. One half of the sample completed the MEPS with the second-person, actual strategy instructions. The other participants completed the MEPS with the third-person, ideal-strategy instructions. The results showed that neither total RRS score, nor its subscale scores were significantly correlated with MEPS scores under either of the two instructions. These findings taken together with previous findings indicate that in nonclinical populations, trait rumination is not related to the effectiveness of problem solving strategies, but that state rumination while responding to the MEPS deteriorates the quality of strategies. The correlations between RRS and SPSI-R:S scores indicated that trait rumination in general, and its brooding subcomponent in particular are parts of cognitive and behavioral responses that attempt to avoid negative environmental and negative private events. Results also showed that reflection is a part of active problem solving. PMID- 26900259 TI - Under-approximating loops in C programs for fast counterexample detection. AB - Many software model checkers only detect counterexamples with deep loops after exploring numerous spurious and increasingly longer counterexamples. We propose a technique that aims at eliminating this weakness by constructing auxiliary paths that represent the effect of a range of loop iterations. Unlike acceleration, which captures the exact effect of arbitrarily many loop iterations, these auxiliary paths may under-approximate the behaviour of the loops. In return, the approximation is sound with respect to the bit-vector semantics of programs. Our approach supports arbitrary conditions and assignments to arrays in the loop body, but may as a result introduce quantified conditionals. To reduce the resulting performance penalty, we present two quantifier elimination techniques specially geared towards our application. Loop under-approximation can be combined with a broad range of verification techniques. We paired our techniques with lazy abstraction and bounded model checking, and evaluated the resulting tool on a number of buffer overflow benchmarks, demonstrating its ability to efficiently detect deep counterexamples in C programs that manipulate arrays. PMID- 26900258 TI - Smart Cup: A Minimally-Instrumented, Smartphone-Based Point-of-Care Molecular Diagnostic Device. AB - Nucleic acid amplification-based diagnostics offer rapid, sensitive, and specific means for detecting and monitoring the progression of infectious diseases. However, this method typically requires extensive sample preparation, expensive instruments, and trained personnel. All of which hinder its use in resource limited settings, where many infectious diseases are endemic. Here, we report on a simple, inexpensive, minimally-instrumented, smart cup platform for rapid, quantitative molecular diagnostics of pathogens at the point of care. Our smart cup takes advantage of water-triggered, exothermic chemical reaction to supply heat for the nucleic acid-based, isothermal amplification. The amplification temperature is regulated with a phase-change material (PCM). The PCM maintains the amplification reactor at a constant temperature, typically, 60-65 degrees C, when ambient temperatures range from 12 to 35 degrees C. To eliminate the need for an optical detector and minimize cost, we use the smartphone's flashlight to excite the fluorescent dye and the phone camera to record real-time fluorescence emission during the amplification process. The smartphone can concurrently monitor multiple amplification reactors and analyze the recorded data. Our smart cup's utility was demonstrated by amplifying and quantifying herpes simplex virus type 2 (HSV-2) with LAMP assay in our custom-made microfluidic diagnostic chip. We have consistently detected as few as 100 copies of HSV-2 viral DNA per sample. Our system does not require any lab facilities and is suitable for use at home, in the field, and in the clinic, as well as in resource-poor settings, where access to sophisticated laboratories is impractical, unaffordable, or nonexistent. PMID- 26900260 TI - Synthesis of Novel C-Pivot Lariat 18-Crown-6 Ethers and their Efficient Purification. AB - The syntheses of various lariat ethers including several not previously reported and their efficient purification are presented. The synthesis route brings together reactions from a variety of previous works leading to a robust and generalized approach to these C-pivot lariats. The main steps are condensation of functionalized diols with pentaethylene glycol ditosylate in the presence of potassium as a templating cation. Purification of the final products was achieved without chromatography by extracting from an aqueous potassium hydroxide solution. PMID- 26900261 TI - Pulsed Rydberg four-wave mixing with motion-induced dephasing in a thermal vapor. AB - We report on time-resolved pulsed four-wave mixing (FWM) signals in a thermal Rubidium vapor involving a Rydberg state. We observe FWM signals with dephasing times up to 7 ns, strongly dependent on the excitation bandwidth to the Rydberg state. The excitation to the Rydberg state is driven by a pulsed two-photon transition on ns timescales. Combined with a cw de-excitation laser, a strongly directional and collective emission is generated according to a combination of the phase matching effect and averaging over Doppler classes. In contrast to a previous report (Huber et al. in Phys Rev A 90: 053806, 2014) using off-resonant FWM, at a resonant FWM scheme we observe additional revivals of the signal shortly after the incident pulse has ended. We infer that this is a revival of motion-induced constructive interference between the coherent emissions of the thermal atoms. The resonant FWM scheme reveals a richer temporal structure of the signals, compared to similar, but off-resonant excitation schemes. A simple explanation lies in the selectivity of Doppler classes. Our numerical simulations based on a four-level model including a whole Doppler ensemble can qualitatively describe the data. PMID- 26900263 TI - Observed changes in the Earth's dynamic oblateness from GRACE data and geophysical models. AB - A new methodology is proposed to estimate changes in the Earth's dynamic oblateness ([Formula: see text] or equivalently, [Formula: see text]) on a monthly basis. The algorithm uses monthly Gravity Recovery and Climate Experiment (GRACE) gravity solutions, an ocean bottom pressure model and a glacial isostatic adjustment (GIA) model. The resulting time series agree remarkably well with a solution based on satellite laser ranging (SLR) data. Seasonal variations of the obtained time series show little sensitivity to the choice of GRACE solutions. Reducing signal leakage in coastal areas when dealing with GRACE data and accounting for self-attraction and loading effects when dealing with water redistribution in the ocean is crucial in achieving close agreement with the SLR based solution in terms of de-trended solutions. The obtained trend estimates, on the other hand, may be less accurate due to their dependence on the GIA models, which still carry large uncertainties. PMID- 26900262 TI - Randomized controlled trials: still the backbone of vascular surgery? AB - Prior to the introduction of evidence-based medicine, decision-making was largely based upon 'intuitive reasoning', whereby senior clinicians dictated practice based upon personal dogma, personal experience and (often) biased observational studies. This era began to end (in vascular surgery) following completion of the landmark randomized trials in carotid disease, which recruited patients throughout the 1980s. Despite scepticism amongst some surgeons of the time these particular randomized trials have stood the test of time and remain the cornerstone of virtually every guideline of practice to this day. The carotid randomized trials became a beacon for using 'evidence' rather than 'intuitive reasoning' and randomized trials have now been used to determine optimal practice in a plethora of carotid surgery and stenting trials, lower limb revascularization and numerous aortic aneurysm based studies. The literature abounds with situations where practice (previously based on observational study data) was changed overnight following publication of a well-designed randomized trial. However, while observational studies are prone to selection bias, randomized trials bring their own unique limitations including problems with external validity, they take too long to complete, they are very expensive, they are notorious for problems with recruitment and they can frequently become obsolete. This has led to a (not unreasonable) call for more observational studies to be used in the development of practice guidelines. Unfortunately, the principle guideline bodies around the world, e.g. National Institute for Health and Care Excellence (NICE) and the American Heart Association (AHA), prioritize randomized trial evidence above all else. Until that changes, guideline makers will find it very difficult to deviate from using historical randomized trial evidence, even when high quality observational data suggest that 'real world' practice bears little comparison to that reported in the randomized trials. Nowhere is that more evident than in developing contemporary guidelines for the management of asymptomatic carotid disease. PMID- 26900264 TI - From facial expressions to bodily gestures: Passions, photography and movement in French 19th-century sciences. AB - This article aims to determine to what extent photographic practices in psychology, psychiatry and physiology contributed to the definition of the external bodily signs of passions and emotions in the second half of the 19th century in France. Bridging the gap between recent research in the history of emotions and photographic history, the following analyses focus on the photographic production of scientists and photographers who made significant contributions to the study of expressions and gestures, namely Duchenne de Boulogne, Charles Darwin, Paul Richer and Albert Londe. This article argues that photography became a key technology in their works due to the adequateness of the exposure time of different cameras to the duration of the bodily manifestations to be recorded, and that these uses constituted facial expressions and bodily gestures as particular objects for the scientific study. PMID- 26900265 TI - Eccentricity error identification and compensation for high-accuracy 3D optical measurement. AB - The circular target has been widely used in various three-dimensional optical measurements, such as camera calibration, photogrammetry and structured light projection measurement system. The identification and compensation of the circular target systematic eccentricity error caused by perspective projection is an important issue for ensuring accurate measurement. This paper introduces a novel approach for identifying and correcting the eccentricity error with the help of a concentric circles target. Compared with previous eccentricity error correction methods, our approach does not require taking care of the geometric parameters of the measurement system regarding target and camera. Therefore, the proposed approach is very flexible in practical applications, and in particular, it is also applicable in the case of only one image with a single target available. The experimental results are presented to prove the efficiency and stability of the proposed approach for eccentricity error compensation. PMID- 26900267 TI - Dopamine and Furosemide for the Treatment of Hepatorenal Syndrome: A Reappraisal or Just Smoke and Mirrors? PMID- 26900266 TI - Model-based clustering based on sparse finite Gaussian mixtures. AB - In the framework of Bayesian model-based clustering based on a finite mixture of Gaussian distributions, we present a joint approach to estimate the number of mixture components and identify cluster-relevant variables simultaneously as well as to obtain an identified model. Our approach consists in specifying sparse hierarchical priors on the mixture weights and component means. In a deliberately overfitting mixture model the sparse prior on the weights empties superfluous components during MCMC. A straightforward estimator for the true number of components is given by the most frequent number of non-empty components visited during MCMC sampling. Specifying a shrinkage prior, namely the normal gamma prior, on the component means leads to improved parameter estimates as well as identification of cluster-relevant variables. After estimating the mixture model using MCMC methods based on data augmentation and Gibbs sampling, an identified model is obtained by relabeling the MCMC output in the point process representation of the draws. This is performed using [Formula: see text] centroids cluster analysis based on the Mahalanobis distance. We evaluate our proposed strategy in a simulation setup with artificial data and by applying it to benchmark data sets. PMID- 26900268 TI - Randomized Controlled Trial Comparing the Efficacy of Terlipressin and Albumin with a Combination of Concurrent Dopamine, Furosemide, and Albumin in Hepatorenal Syndrome. AB - BACKGROUND: Terlipressin with albumin is recommended in hepatorenal syndrome (HRS). Terlipressin is expensive and not licensed in many countries. Alternative therapy is necessary. We compared the efficacy of terlipressin and albumin with concurrent low-dose dopamine, furosemide, and albumin in HRS. METHODS: In an open label, randomized trial, forty consecutive patients each with HRS type I and HRS type II received either concurrent infusion of terlipressin 0.5 mg for every 6 hr and albumin 20 g/day for 5 days (n = 20) or a combination of dopamine 2 MUg/kg/min, furosemide 0.01 mg/kg/hr, and albumin 20 g/day (triple therapy), in one of two therapeutic arms. Twenty-four-hour urine output, urinary sodium, and plasma renin activity (PRA) were assessed before and after treatment. RESULTS: The two groups were comparable at baseline in both HRS-I and II. In HRS-I, 24 hr urine output and urine sodium at the end of 5 days increased in both treatment groups (terlipressin, urine output 278 +/- 136 to 765 +/- 699 ml/day, P < 0.01; urine sodium 28 +/- 25.1 to 39 +/- 32.1 meq/l, P = 0.05. Triple therapy: urine output 219 +/- 134 to 706 +/- 595 ml/day, P < 0.01; urine sodium 25 +/- 18.3 to 41 +/- 27.5 meq/l, P < 0.01). PRA (ng/ml/hr) decreased from 28.1 +/- 9.76 to 24.2 +/- 9.5 (P = 0.01) and from 29.5 +/- 15.8 to 27.3 +/- 17.1 (P = 0.02) in the terlipressin and triple therapy groups, respectively. In HRS-II, similar significant improvement (P < 0.01) was seen in 24 hr urine output and urine sodium; decrease in PRA (P < 0.05) was documented after treatment in both the arms. Post-treatment changes in parameters were comparable between the two arms, in both HRS-I and HRS-II cases. CONCLUSIONS: Concurrent triple therapy improved renal function in HRS and was less expensive than terlipressin (Registration: CTRI/2011/07/001860; www.ctri.nic.in). PMID- 26900269 TI - Plasma Lipid Profiling in a Rat Model of Hepatocellular Carcinoma: Potential Modulation Through Quinolone Administration. AB - BACKGROUND/AIMS: The primary aim of this study was to characterise the blood metabolic profile of hepatocellular carcinoma (HCC) in a rat model, and the secondary aim was to evaluate the effect of the quinolone, norfloxacin on metabolic profiles and exploring the role that gut sterilisation may have on HCC development. METHODS: HCC was induced in 10 Fischer rats by administration of intra-peritoneal diethylnitrosamine (DEN) and oral N-nitrosomorpholine. Plasma was collected upon sacrifice. Five of these rats were concomitantly administered oral norfloxacin. Six Fischer non-treated rats acted as healthy controls. Proton nuclear magnetic resonance (NMR) spectra were acquired using a 600 MHz NMR system. RESULTS: Control animals were 120 g heavier than diseased counterparts. Proton NMR spectra from diseased rats displayed significant decreases in lipoproteins, unsaturated fatty acids, acetyl-glycoprotein, acetoacetate, and glucose (P <= 0.001). Plasma citrate and formate levels were increased (P = 0.02). Norfloxacin appeared to abrogate this effect slightly. CONCLUSION: The spectral profiles of plasma in rats with HCC display marked changes with relation to lipid metabolism and cellular turnover. Norfloxacin appears to moderate these metabolic alterations to a small degree. PMID- 26900270 TI - Risk Factors Associated With Non-Alcoholic Fatty Liver Disease in Indians: A Case Control Study. AB - BACKGROUND/AIMS: NAFLD has today emerged as the leading cause of liver disorder. There is scanty data on risk factors associated with NAFLD emanating from India. The present study was conducted to identify the risk factors associated with NAFLD. METHODS: 464 consecutive NAFLD patients and 181 control patients were subjected to detailed questionnaire regarding their lifestyle and dietary risk factors. Anthropometric measurements were obtained and biochemical assays were done. Comparison of different variables was made between NAFLD patients and controls using principal component analysis (PCA). RESULTS: NAFLD patients had higher BMI [26.25 +/- 3.80 vs 21.46 +/- 3.08 kg/m(2), P = 0.000], waist-hip ratio [0.96 +/- 0.12 vs 0.90 +/- 0.08, P = 0.000] and waist-height ratio [0.57 +/- 0.09 vs 0.50 +/- 0.06, P = 0.000] compared to controls. Fasting blood sugar [101.88 +/ 31.57 vs 90.87 +/- 10.74 mg/dl] and triglyceride levels [196.16 +/- 102.66 vs 133.20 +/- 58.37 mg/dl] were significantly higher in NAFLD group. HOMA-IR was also higher in NAFLD group [2.53 +/- 2.57 vs 1.16 +/- 0.58, P = 0.000]. Majority (90.2%) of NAFLD patients were sedentary. Family history of metabolic syndrome (MS) was positively correlated with NAFLD. Dietary risk factors associated with NAFLD were non-vegetarian diet [35% vs 23%, P = 0.002], fried food [35% vs 9%, P = 0.000], spicy foods [51% vs 15%, P = 0.001] and tea [55% vs 39%, P = 0.001]. Diabetes, hypertension, snoring and sleep apnoea syndrome were common factors in NAFLD. On multivariate PCA, waist/height ratio and BMI were significantly higher in the NAFLD patients. CONCLUSION: The risk factors associated with NAFLD are sedentary lifestyle, obesity family history of MS, consumption of meat/fish, spicy foods, fried foods and tea. Other risk factors associated with NAFLD included snoring and MS. PMID- 26900271 TI - Role of Transient Elastography (Fibroscan) in Differentiating Severe Acute Hepatitis and Acute on Chronic Liver Failure. AB - INTRODUCTION: It is difficult to differentiate acute severe hepatitis (AH) with acute on chronic liver failure (ACLF). Aim was to study the role of transient elastography (Fibroscan) in identifying the patients with AH and ACLF. MATERIALS AND METHODS: Consecutive patients of severe AH or ACLF presented within two weeks of jaundice were enrolled. LSM and liver function tests were done at admission, week 1, 4 and at 6 months. Diagnosis of ACLF was based on documenting cirrhotic morphology on imaging and/or liver biopsy and follow-up of these patients for six months. Similarly, AH patients were diagnosed based on serology, no features of cirrhosis on imaging and follow-up of these patients for 6 months documenting reversal of liver stiffness measurement (LSM) to normal. RESULTS: 104 patients were included in the final analysis (AH, n = 59, ACLF, n = 45). Out of 59 patients in severe AH group, etiology of acute hepatitis included hepatitis A (HAV, n = 22), hepatitis E (HEV, n = 21), hepatitis B (HBV, n = 4), indeterminate (n = 8) and drug induced liver injury (n = 4). Similarly for ACLF, the causes of chronic liver disease were alcohol (n = 26), hepatitis B (n = 7), hepatitis C (n = 2) and cryptogenic (n = 10). Patients with ACLF were significantly older, had low hemoglobin, low albumin, high bilirubin and lower transaminases level compared to severe AH at admission. LSM was higher in patients with ACLF compared to severe AH (61 +/- 18 kPa vs 15 +/- 6.4 kPa, P = 0.001) at admission. On multivariate analysis of noninvasive tests only LSM was found to differentiate AH with ACLF significantly. When we took a cutoff of 26 kPa the sensitivity and specificity of diagnosis of ACLF were 96% and 93%, respectively, with area under the curve was 0.98 (0.95-1.005), P = 0.001. CONCLUSION: LSM could differentiate patients with severe AH and ACLF at admission. PMID- 26900272 TI - Safety of Ascitic Paracentesis in Patients with Budd-Chiari Syndrome on Oral Anticoagulation and Elevated International Normalized Ratio. AB - BACKGROUND/AIMS: Anticoagulation is the standard of care in patients with Budd Chiari Syndrome (BCS). Ascites is a common symptom in patients with BCS. Often such patients require paracentesis while taking oral anticoagulation concurrently. It is unclear whether paracentesis leads to increased bleeding in such patients or whether anticoagulation has to be temporarily suspended. We describe our experience with paracentesis in patients with BCS taking oral anticoagulation. METHODS: Our study subjects included consecutive patients with BCS with ascites on oral anticoagulation admitted between 2007 and 2011. The dose of oral anticoagulation was titrated to achieve international normalized ratio (INR) between 2 and 3. Routine hematological tests included Factor VIII (FVIII) levels. Paracentesis was undertaken without the prior administration of fresh frozen plasma and without the aid of ultrasonography. We looked for occurrences of bleeding at the puncture site or hemoperitoneum during and after the procedure. RESULTS: Thirty-two of the 60 patients with BCS patients taking oral anticoagulation concurrently developed ascites. Thirty among 32 patients required paracentesis on one or more occasions. A total of 51 paracentesis procedures were performed (Median 1.6, Range 1-7). The mean INR was 3.1 (Range 1.4-7.9). No patient developed bleeding or hemoperitoneum. The mean FVIII measured was 138.8% of laboratory control and mean platelet level was 2.2 * 10(5)/ml. CONCLUSIONS: Ascitic paracentesis in patients with BCS on anticoagulation is safe without an increased risk of abdominal wall bleeding or hemoperitoneum. Normal or high FVIII and platelet levels likely mitigate against bleeding risks. PMID- 26900273 TI - Indications of Liver Biopsy in the Era of Noninvasive Assessment of Liver Fibrosis. AB - BACKGROUND: Liver biopsy (LB) has been used as diagnostic modality in liver diseases (LD). Over last two decades, there has been remarkable improvement in understanding of natural history, molecular diagnostics of viral hepatitis, genetic of LD, and also limitations of LB. There is current trend in avoiding LB in the management of various LDs. AIM: To determine utility of LB in clinical practice. MATERIAL AND METHODS: In a prospective study, 2413 patients of LD were followed up, 219 (9%) were acute, and remaining 2194 (90.9%) were chronic LD. Patients were evaluated by biochemical parameters, virological studies, and imaging endoscopy as and when required. LB was performed in 176 (7.2%) patients when no conclusion could be drawn from the noninvasive workup. Patients with platelet count <50,000/cm(2), ascites, and overt bleeding were excluded. Patients with international normalization ratio (INR) more than 1.5 were not excluded. No prophylactic use of fresh frozen plasma and platelet transfusion was done. There was no major complication related to the procedure. Indications for LB were as follows: cryptogenic LD 38 cases, hepatitis B infection 35, suspected autoimmune hepatitis 30, mass lesion in the liver and lymphoma 29, evaluation of portal hypertension 15, elevated liver enzymes 11, hepatitis C infection 9, and drug induced LD 4, and miscellaneous 5 cases which were primary biliary cholangitis, primary sclerosing cholangitis, cholestatic LD, sarcoidosis, and amyloidosis. RESULTS: LB changed the diagnosis in 55 (31.2%). These were cryptogenic LD in 24 cases, portal hypertension 15, elevated liver enzymes 11, and 5 others. In remaining, LB confirmed clinical diagnosis and helped in making management decisions. CONCLUSION: LB was required in 7.2% of patients with chronic LD. In 31.2% cases, LB changed the diagnosis. LB was a safe procedure even in presence of low platelet count and abnormal INR. PMID- 26900274 TI - Magnetic Resonance Spectroscopy: Principles and Techniques: Lessons for Clinicians. AB - Magnetic resonance spectroscopy (MRS) provides a non-invasive 'window' on biochemical processes within the body. Its use is no longer restricted to the field of research, with applications in clinical practice increasingly common. MRS can be conducted at high magnetic field strengths (typically 11-14 T) on body fluids, cell extracts and tissue samples, with new developments in whole-body magnetic resonance imaging (MRI) allowing clinical MRS at the end of a standard MRI examination, obtaining functional information in addition to anatomical information. We discuss the background physics the busy clinician needs to know before considering using the technique as an investigative tool. Some potential applications of hepatic and cerebral MRS in chronic liver disease are also discussed. PMID- 26900275 TI - Liver Transplantation in India: At the Crossroads. AB - As the liver transplant journey in India reaches substantial numbers and suggests quality technical expertise, it is time to dispassionately look at the big picture, identify problems, and consider corrective measures for the future. Several features characterize the current scenario. Although the proportion of deceased donor liver transplants is increasing, besides major regional imbalances, the activity is heavily loaded in favor of the private sector and live donor transplants. The high costs of the procedure, the poor participation of public hospitals, the lack of a national registry, and outcomes reporting are issues of concern. Organ sharing protocols currently based on chronology or institutional rotation need to move to a more justiciable severity-based system. Several measures can expand the deceased donor pool. The safety of the living donor continues to need close scrutiny and focus. Multiple medical challenges unique to the Indian situation are also being thrown up. Although many of the deficits demand state intervention and policy changes the transplant community needs to take notice and highlight them. The future of liver transplantation in India should move toward a more accountable, equitable, and accessible form. We owe this to our citizens who have shown tremendous faith in us by volunteering to be living donors as well as consenting for deceased donation. PMID- 26900276 TI - Primary Liver Sinusoidal Non-Hodgkin's Lymphoma Presenting as Acute Liver Failure. AB - We describe a case of a middle-aged woman, who presented to us with fever, anorexia, abdominal distension from a massive hepatomegaly, low hemoglobin, and acute liver failure. A liver biopsy revealed B cell non-Hodgkin's lymphoma predominantly in the sinusoids with CD10, CD20, and Bcl-2 positive on immunohistochemistry. She initially responded well to chemotherapy but succumbed 6 months later to the recurrence of disease. Sinusoidal non-Hodgkin's lymphoma of the liver should be considered in the differential diagnosis of a patient with large hepatomegaly presenting with acute liver failure. PMID- 26900277 TI - Liver Transplantation After Bone Marrow Transplantation for End Stage Liver Disease with Severe Hepatopulmonary Syndrome in Dyskeratosis Congenita: A Literature First. AB - Dyskeratosis congenita is a multisystem genetic disorder. Although hepatic involvement is reported in about 7% of patients with dyskeratosis congenita, it is not well characterized and often attributed to hemochromatosis from frequent blood transfusions. A few case reports describe cirrhosis and hepatic cell necrosis in affected individuals in autosomal dominant pedigrees. Bone marrow failure and malignancies are the principal causes of death in dyskeratosis congenita. We describe the first case of living donor liver transplantation, in dyskeratosis congenita for decompensated cirrhosis with portal hypertension. The patient also had associated severe hepatopulmonary syndrome, interstitial lung disease, bilateral hip replacement for avascular necrosis of the head of femur, and a past history of bone marrow transplantation for bone marrow failure. PMID- 26900278 TI - Upper Gastrointestinal Bleed Following Percutaneous Liver Abscess Drainage. PMID- 26900279 TI - Use of Non-selective Beta-blockers in Decompensated Cirrhosis: Controversy Continues. PMID- 26900280 TI - Hepatobiliary Quiz (Answers)-16 (2015). PMID- 26900281 TI - Pharmacological cyclin dependent kinase inhibitors: Implications for colorectal cancer. AB - Colorectal cancer accounts for a significant proportion of cancer deaths worldwide. The need to develop more chemotherapeutic agents to combat this disease is critical. Cyclin dependent kinases (CDKs), along with its binding partner cyclins, serve to control the growth of cells through the cell cycle. A new class of drugs, termed CDK inhibitors, has been studied in preclinical and now clinical trials. These inhibitors are believed to act as an anti-cancer drug by blocking CDKs to block the uncontrolled cellular proliferation that is hallmark of cancers like colorectal cancer. CDK article provides overview of the emerging drug class of CDK inhibitors and provides a list of ones that are currently in clinical trials. PMID- 26900282 TI - Diagnostic imaging and radiation exposure in inflammatory bowel disease. AB - Diagnostic imaging plays a key role in the diagnosis and management of inflammatory bowel disease (IBD). However due to the relapsing nature of IBD, there is growing concern that IBD patients may be exposed to potentially harmful cumulative levels of ionising radiation in their lifetime, increasing malignant potential in a population already at risk. In this review we explore the proportion of IBD patients exposed to high cumulative radiation doses, the risk factors associated with higher radiation exposures, and we compare conventional diagnostic imaging with newer radiation-free imaging techniques used in the evaluation of patients with IBD. While computed tomography (CT) performs well as an imaging modality for IBD, the effective radiation dose is considerably higher than other abdominal imaging modalities. It is increasingly recognised that CT imaging remains responsible for the majority of diagnostic medical radiation to which IBD patients are exposed. Magnetic resonance imaging (MRI) and small intestine contrast enhanced ultrasonography (SICUS) have now emerged as suitable radiation-free alternatives to CT imaging, with comparable diagnostic accuracy. The routine use of MRI and SICUS for the clinical evaluation of patients with known or suspected small bowel Crohn's disease is to be encouraged wherever possible. More provision is needed for out-of-hours radiation-free imaging modalities to reduce the need for CT. PMID- 26900283 TI - Diet therapy for inflammatory bowel diseases: The established and the new. AB - Although patients with inflammatory bowel diseases (IBD) have a strong interest in dietary modifications as part of their therapeutic management, dietary advice plays only a minor part in published guidelines. The scientific literature shows that dietary factors might influence the risk of developing IBD, that dysbiosis induced by nutrition contributes to the pathogenesis of IBD, and that diet may serve as a symptomatic treatment for irritable bowel syndrome-like symptoms in IBD. The role of nutrition in IBD is underscored by the effect of various dietary therapies. In paediatric patients with Crohn's disease (CD) enteral nutrition (EN) reaches remission rates similar to steroids. In adult patients, however, EN is inferior to corticosteroids. EN is not effective in ulcerative colitis (UC). Total parenteral nutrition in IBD is not superior to steroids or EN. The use of specific probiotics in patients with IBD can be recommended only in special clinical situations. There is no evidence for efficacy of probiotics in CD. By contrast, studies in UC have shown a beneficial effect in selected patients. For patients with pouchitis, antibiotic treatment followed by probiotics, like VSL#3 or Lactobacillus GG, is effective. When probiotics are used, the risk of bacterial translocation and subsequent bacteremia has to be considered. More understanding of the normal intestinal microflora, and better characterization of probiotic strains at the phenotypic and genomic levels is needed as well as clarification of the mechanisms of action in different clinical settings. A FODMAP reduced diet may improve symptoms in IBD. PMID- 26900284 TI - Role of regulatory T cell in the pathogenesis of inflammatory bowel disease. AB - Regulatory T (Treg) cells play key roles in various immune responses. For example, Treg cells contribute to the complex pathogenesis of inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis during onset or development of that disease. Many animal models of IBD have been used to investigate factors such as pathogenic cytokines, pathogenic bacteria, and T-cell functions, including those of Treg cells. In addition, analyses of patients with IBD facilitate our understanding of the precise mechanism of IBD. This review article focuses on the role of Treg cells and outlines the pathogenesis and therapeutic strategies of IBD based on previous reports. PMID- 26900285 TI - miRNAs as new molecular insights into inflammatory bowel disease: Crucial regulators in autoimmunity and inflammation. AB - Inflammatory bowel disease (IBD) is characterized by chronic relapsing inflammatory disorders of the gastrointestinal tract, and includes two major phenotypes: ulcerative colitis and Crohn's disease. The pathogenesis of IBD is not fully understood as of yet. It is believed that IBD results from complicated interactions between environmental factors, genetic predisposition, and immune disorders. miRNAs are a class of small non-coding RNAs that can regulate gene expression by targeting the 3'-untranslated region of specific mRNAs for degradation or translational inhibition. miRNAs are considered to play crucial regulatory roles in many biologic processes, such as immune cellular differentiation, proliferation, and apoptosis, and maintenance of immune homeostasis. Recently, aberrant expression of miRNAs was revealed to play an important role in autoimmune diseases, including IBD. In this review, we discuss the current understanding of how miRNAs regulate autoimmunity and inflammation by affecting the differentiation, maturation, and function of various immune cells. In particular, we focus on describing specific miRNA expression profiles in tissues and peripheral blood that may be associated with the pathogenesis of IBD. In addition, we summarize the opportunities for utilizing miRNAs as new biomarkers and as potential therapeutic targets in IBD. PMID- 26900288 TI - Management of pancreatic fluid collections: A comprehensive review of the literature. AB - Pancreatic fluid collections (PFCs) are a frequent complication of pancreatitis. It is important to classify PFCs to guide management. The revised Atlanta criteria classifies PFCs as acute or chronic, with chronic fluid collections subdivided into pseudocysts and walled-off pancreatic necrosis (WOPN). Establishing adequate nutritional support is an essential step in the management of PFCs. Early attempts at oral feeding can be trialed in patients with mild pancreatitis. Enteral feeding should be implemented in patients with moderate to severe pancreatitis. Jejunal feeding remains the preferred route of enteral nutrition. Symptomatic PFCs require drainage; options include surgical, percutaneous, or endoscopic approaches. With the advent of newer and more advanced endoscopic tools and expertise, and an associated reduction in health care costs, minimally invasive endoscopic drainage has become the preferable approach. An endoscopic ultrasonography-guided approach using a seldinger technique is the preferred endoscopic approach. Both plastic stents and metal stents are efficacious and safe; however, metal stents may offer an advantage, especially in infected pseudocysts and in WOPN. Direct endoscopic necrosectomy is often required in WOPN. Lumen apposing metal stents that allow for direct endoscopic necrosectomy and debridement through the stent lumen are preferred in these patients. Endoscopic retrograde cholangio pancreatography with pancreatic duct (PD) exploration should be performed concurrent to PFC drainage. PD disruption is associated with an increased severity of pancreatitis, an increased risk of recurrent attacks of pancreatitis and long-term complications, and a decreased rate of PFC resolution after drainage. Any pancreatic ductal disruption should be bridged with endoscopic stenting. PMID- 26900287 TI - Inflammation in irritable bowel syndrome: Myth or new treatment target? AB - Low-grade intestinal inflammation plays a key role in the pathophysiology of irritable bowel syndrome (IBS), and this role is likely to be multifactorial. The aim of this review was to summarize the evidence on the spectrum of mucosal inflammation in IBS, highlighting the relationship of this inflammation to the pathophysiology of IBS and its connection to clinical practice. We carried out a bibliographic search in Medline and the Cochrane Library for the period of January 1966 to December 2014, focusing on publications describing an interaction between inflammation and IBS. Several evidences demonstrate microscopic and molecular abnormalities in IBS patients. Understanding the mechanisms underlying low-grade inflammation in IBS may help to design clinical trials to test the efficacy and safety of drugs that target this pathophysiologic mechanism. PMID- 26900290 TI - Genomic characterization of esophageal squamous cell carcinoma: Insights from next-generation sequencing. AB - Two major types of cancer occur in the esophagus: squamous cell carcinoma, which is associated with chronic smoking and alcohol consumption, and adenocarcinoma, which typically arises in gastric reflux-associated Barrett's esophagus. Although there is increasing incidence of esophageal adenocarcinoma in Western counties, esophageal squamous cell carcinoma (ESCC) accounts for most esophageal malignancies in East Asia, including China and Japan. Technological advances allowing for massively parallel, high-throughput next-generation sequencing (NGS) of DNA have enabled comprehensive characterization of somatic mutations in large numbers of tumor samples. Recently, several studies were published in which whole exome or whole genome sequencing was performed in ESCC tumors and compared with matched normal DNA. Mutations were validated in several genes, including in TP53, CDKN2A, FAT1, NOTCH1, PIK3CA, KMT2D and NFE2L2, which had been previously implicated in ESCC. Several new recurrent alterations have also been identified in ESCC. Combining the clinicopathological characteristics of patients with information obtained from NGS studies may lead to the development of effective diagnostic and therapeutic approaches for ESCC. As this research becomes more prominent, it is important that gastroenterologist become familiar with the various NGS technologies and the results generated using these methods. In the present study, we describe recent research approaches using NGS in ESCC. PMID- 26900291 TI - Role of Tim-3 in hepatitis B virus infection: An overview. AB - Hepatitis B virus (HBV) infection has received increasing public attention. HBV is the prototypical member of hepadnaviruses, which naturally infect only humans and great apes and induce the acute and persistent chronic infection of hepatocytes. A large body of evidence has demonstrated that dysfunction of the host anti-viral immune response is responsible for persistent HBV replication, unresolved inflammation and disease progression. Many regulatory factors are involved in immune dysfunction. Among these, T cell immunoglobulin domain and mucin domain-3 (Tim-3), one of the immune checkpoint proteins, has attracted increasing attention due to its critical role in regulating both adaptive and innate immune cells. In chronic HBV infection, Tim-3 expression is elevated in many types of immune cells, such as T helper cells, cytotoxic T lymphocytes, dendritic cells, macrophages and natural killer cells. Tim-3 over-expression is often accompanied by impaired function of the above-mentioned immunocytes, and Tim-3 inhibition can at least partially rescue impaired immune function and thus promote viral clearance. A better understanding of the regulatory role of Tim-3 in host immunity during HBV infection will shed new light on the mechanisms of HBV-related liver disease and suggest new therapeutic methods for intervention. PMID- 26900289 TI - Hepatitis E virus: An ancient hidden enemy in Latin America. AB - Hepatitis E virus (HEV) infection is a common cause of acute clinical hepatitis worldwide. HEV is an RNA-containing virus and the only member of the genus Hepevirus in the family Hepeviridae. Human HEV is classified into four genotypes widely distributed across the world. The virus is mainly transmitted via the fecal-oral route, and water-borne epidemics have become characteristic of hepatitis E in developing countries, including those in Latin America. The zoonotic potential of HEV is broadly recognized. Thus, there is an urgent need to re-evaluate virus transmission scenarios and to enforce epidemiological surveillance systems. Additionally, it is known that HEV infections, initially defined as self-limiting, can also take chronic courses in immunocompromised patients. Moreover, we recently reported a high seroprevalence of HEV in samples from cirrhotic patients with no other etiological agents present, suggesting the potential role of HEV in the development of chronic liver illness. In this review, HEV genomic variability, transmission, chronic infectious course, zoonotic potential and treatment are discussed. Focus is placed on the impact of HEV infection in Latin America, to support the development of specific control strategies and the handling of this important and typically imperceptible viral infection. PMID- 26900292 TI - Chronic pancreatitis: A diagnostic dilemma. AB - Typical clinical symptoms of chronic pancreatitis are vague and non-specific and therefore diagnostic tests are required, none of which provide absolute diagnostic certainly, especially in the early stages of disease. Recently published guidelines bring much needed structure to the diagnostic work-up of patients with suspected chronic pancreatitis. In addition, novel diagnostic modalities bring promise for the future. The assessment and diagnosis of pancreatic exocrine insufficiency remains challenging and this review contests the accepted perspective that steatorrhea only occurs with > 90% destruction of the gland. PMID- 26900286 TI - Gut microbiota role in irritable bowel syndrome: New therapeutic strategies. AB - In the last decade the impressive expansion of our knowledge of the vast microbial community that resides in the human intestine, the gut microbiota, has provided support to the concept that a disturbed intestinal ecology might promote development and maintenance of symptoms in irritable bowel syndrome (IBS). As a correlate, manipulation of gut microbiota represents a new strategy for the treatment of this multifactorial disease. A number of attempts have been made to modulate the gut bacterial composition, following the idea that expansion of bacterial species considered as beneficial (Lactobacilli and Bifidobacteria) associated with the reduction of those considered harmful (Clostridium, Escherichia coli, Salmonella, Shigella and Pseudomonas) should attenuate IBS symptoms. In this conceptual framework, probiotics appear an attractive option in terms of both efficacy and safety, while prebiotics, synbiotics and antibiotics still need confirmation. Fecal transplant is an old treatment translated from the cure of intestinal infective pathologies that has recently gained a new life as therapeutic option for those patients with a disturbed gut ecosystem, but data on IBS are scanty and randomized, placebo-controlled studies are required. PMID- 26900293 TI - Mutation analysis of 13 driver genes of colorectal cancer-related pathways in Taiwanese patients. AB - AIM: To investigate the driver gene mutations associated with colorectal cancer (CRC) in the Taiwanese population. METHODS: In this study, 103 patients with CRC were evaluated. The samples consisted of 66 men and 37 women with a median age of 59 years and an age range of 26-86 years. We used high-resolution melting analysis (HRM) and direct DNA sequencing to characterize the mutations in 13 driver genes of CRC-related pathways. The HRM assays were conducted using the LightCycler(r) 480 Instrument provided with the software LightCycler(r) 480 Gene Scanning Software Version 1.5. We also compared the clinicopathological data of CRC patients with the driver gene mutation status. RESULTS: Of the 103 patients evaluated, 73.79% had mutations in one of the 13 driver genes. We discovered 18 novel mutations in APC, MLH1, MSH2, PMS2, SMAD4 and TP53 that have not been previously reported. Additionally, we found 16 de novo mutations in APC, BMPR1A, MLH1, MSH2, MSH6, MUTYH and PMS2 in cancerous tissues previously reported in the dbSNP database; however, these mutations could not be detected in peripheral blood cells. The APC mutation correlates with lymph node metastasis (34.69% vs 12.96%, P = 0.009) and cancer stage (34.78% vs 14.04%, P = 0.013). No association was observed between other driver gene mutations and clinicopathological features. Furthermore, having two or more driver gene mutations correlates with the degree of lymph node metastasis (42.86% vs 24.07%, P = 0.043). CONCLUSION: Our findings confirm the importance of 13 CRC-related pathway driver genes in the development of CRC in Taiwanese patients. PMID- 26900294 TI - Choledochojejunostomy with an innovative magnetic compressive anastomosis: How to determine optimal pressure? AB - AIM: To investigate the optimal magnetic pressure and provide a theoretical basis for choledochojejunostomy magnetic compressive anastomosis (magnamosis). METHODS: Four groups of neodymium-iron-boron magnets with different magnetic pressures of 0.1, 0.2, 0.3 and 0.4 MPa were used to complete the choledochojejunostomy magnamosis. Twenty-six young mongrel dogs were randomly divided into five groups: four groups with different magnetic pressures and 1 group with a hand-suture anastomosis. Serum bilirubin levels were measured in all groups before and 1 wk, 2 wk, 3 wk, 1 mo and 3 mo after surgery. Daily abdominal X-ray fluoroscopy was carried out postoperatively to detect the path and the excretion of the magnet. The animals were euthanized at 1 or 3 mo after the operation, the burst pressure was detected in each anastomosis, and the gross appearance and histology were compared according to the observation. RESULTS: The surgical procedures were all successfully performed in animals. However, animals of group D (magnetic pressure of 0.4 MPa) all experienced complications with bile leakage (4/4), whereas half of animals in group A (magnetic pressure of 0.1 MPa) experienced complications (3/6), 1 animal in the manual group E developed anastomotic stenosis, and animals in group B and group C (magnetic pressure of 0.2 MPa and 0.3 MPa, respectively) all healed well without complications. These results also suggested that the time required to form the stoma was inversely proportional to the magnetic pressure; however, the burst pressure of group A was smaller than those of the other groups at 1 mo (187.5 +/- 17.7 vs 290 +/- 10/296.7 +/- 5.7/287.5 +/- 3.5, P < 0.05); the remaining groups did not differ significantly. A histologic examination demonstrated obvious differences between the magnamosis groups and the hand-sewn group. CONCLUSION: We proved that the optimal range for choledochojejunostomy magnamosis is 0.2 MPa to 0.3 MPa, which will help to improve the clinical application of this technique in the future. PMID- 26900295 TI - Recurrent colorectal cancer after endoscopic resection when additional surgery was recommended. AB - AIM: To evaluate the type of recurrence after endoscopic resection in colorectal cancer patients and whether rescue was possible by salvage operation. METHODS: Among 4972 patients who underwent surgical resection at our institution for primary or recurrent colorectal cancers from January 2005 to February 2015, we experienced eight recurrent colorectal cancers after endoscopic resection when additional surgical resection was recommended. RESULTS: The recurrence patterns were: intramural local recurrence (five cases), regional lymph node recurrence (three cases), and associated with simultaneous distant metastasis (three cases). Among five cases with lymphatic invasion observed histologically in endoscopic resected specimens, four cases recurred with lymph node metastasis or distant metastasis. All cases were treated laparoscopically and curative surgery was achieved in six cases. Among four cases located in the rectum, three cases achieved preservation of the anus. Postoperative complications occurred in two cases (enteritis). CONCLUSION: For high-risk submucosal invasive colorectal cancers after endoscopic resection, additional surgical resection with lymphadenectomy is recommended, particularly in cases with lymphovascular invasion. PMID- 26900296 TI - Risk factors of biliary intervention by imaging after living donor liver transplantation. AB - AIM: To determine the risk factors of biliary intervention using magnetic resonance cholangiopancreatography (MRCP) after living donor liver transplantation (LDLT). METHODS: We retrospectively enrolled 196 patients who underwent right lobe LDLT between 2006 and 2010 at a single liver transplantation center. Direct duct-to-duct biliary anastomosis was performed in all 196 patients. MRCP images routinely taken 1 mo after LDLT were analyzed to identify risk factors for biliary intervention during follow-up, such as retrograde cholangiopancreatography or percutaneous transhepatic biliary drainage. Two experienced radiologists evaluated the MRCP findings, including the anastomosis site angle on three-dimensional images, the length of the filling defect on maximum intensity projection, bile duct dilatation, biliary stricture, and leakage. RESULTS: Eighty-nine patients underwent biliary intervention during follow-up. The anastomosis site angle [hazard ratio (HR) = 0.48; 95% confidence interval (CI), 0.30-0.75, P < 0.001], a filling defect in the anastomosis site (HR = 2.18, 95%CI: 1.41-3.38, P = 0.001), and biliary leakage (HR = 2.52, 95%CI: 1.02-6.20, P = 0.048) on MRCP were identified in the multivariate analysis as significant risk factors for biliary intervention during follow-up. Moreover, a narrower anastomosis site angle (i.e., below the median angle of 113.3 degrees ) was associated with earlier biliary intervention (38.5 +/- 4.2 mo vs 62. 1 +/- 4.1 mo, P < 0.001). Kaplan-Meier analysis comparing biliary intervention-free survival according to the anastomosis site angle revealed that lower survival was associated with a narrower anastomosis site angle (36.3% vs 62.0%, P < 0.001). CONCLUSION: The biliary anastomosis site angle in MRCP after LDLT may be associated with the need for biliary intervention. PMID- 26900297 TI - Using typical endoscopic features to diagnose esophageal squamous papilloma. AB - AIM: To better understand some of the superficial tiny lesions that are recognized as squamous papilloma of the esophagus (SPE) and receive a different pathological diagnosis. METHODS: All consecutive patients with esophageal polypoid lesions detected by routine endoscopy at our Endoscopy Centre between October 2009 and June 2014 were retrospectively analysed. We enrolled patients with SPE or other superficial lesions to investigate four key endoscopic appearances (whitish color, exophytic growth, wart-like shape, and surface vessels) and used narrow band imaging (NBI) to distinguish their differences. These series endoscopic images of each patient were retrospectively reviewed by three experienced endoscopists with no prior access to the images. All lesion specimens obtained by forceps biopsy were fixed in formalin and processed for pathological examination. The following data were collected from patient medical records: gender, age, indications for esophagogastroduodenoscopy, and endoscopic characteristics including lesion location, number, color, size, surface morphology, surrounding mucosa, and surface vessels under NBI. Clinicopathological features were also compared. RESULTS: During the study period, 41 esophageal polypoid lesions from 5698 endoscopic examinations were identified retrospectively. These included 24 patients with pathologically confirmed SPE, 11 patients with squamous hyperplasia, three patients with glycogenic acanthosis, two patients with ectopic sebaceous glands, and one patient with a xanthoma. In the chi (2) test, exophytic growth (P = 0.003), a wart-like shape (P < 0.001), and crossing surface vessels under NBI (P = 0.001) were more frequently observed in SPE than in other lesion types. By contrast, there was no significant difference regarding the appearance of a whitish color between SPE and other lesion types (P = 0.872). The most sensitive characteristic was wart-like projections (81.3%) and the most specific was exophytic growth (87.5%). Promising positive predictive values of 84.2%, 80.8%, and 82.6% were noted for exophytic growth, wart-like projections, and surface vessel crossing on NBI, respectively. CONCLUSION: The use of three key typical endoscopic appearances--exophytic growth, a wart-like shape, and vessel crossing on the lesion surface under NBI--has a promising positive predictive value of 88.2%. This diagnostic triad is useful for the endoscopic diagnosis of SPE. PMID- 26900298 TI - Effects of endoplasmic reticulum stress on the expression of inflammatory cytokines in patients with ulcerative colitis. AB - AIM: To explore the changes of X-box binding protein 1 splicing (XBP1s) and inflammatory cytokine expression in patients with ulcerative colitis (UC) in response to endoplasmic reticulum stress (ERS). METHODS: Reverse transcription polymerase chain reaction and quantitative polymerase chain reaction were performed to detect the forms of XBP1s and the expression of interleukin (IL)-2, interferon (IFN)-gamma, and IL-17alpha. Differences between patients with UC and normal subjects were then determined. RESULTS: Mononuclear cells of the peripheral blood of normal subjects and UC patients with were stimulated with no drugs (control), phytohemagglutinin (PHA), thapsigargin (TG), or both PHA and TG. XBP1s in patients with UC exhibited splicing, which was greater with co stimulation than single stimulation. Co-stimulation increased the expression level of IL-2, IFN-gamma, and IL-17alpha. CONCLUSION: The T lymphocytes of both normal subjects and patients with UC responded to ERS by activating the XBP1s mediated signalling pathway, upregulating the expression of inflammatory cytokines, and increasing the occurrence of inflammation. The mononuclear cells in the peripheral blood of patients with UC were more sensitive to ERS than those in the peripheral blood of normal subjects. PMID- 26900299 TI - Endoscopic dilation of complete oesophageal obstructions with a combined antegrade-retrograde rendezvous technique. AB - AIM: To investigate the combined antegrade-retrograde endoscopic rendezvous technique for complete oesophageal obstruction and the swallowing outcome. METHODS: This single-centre case series includes consecutive patients who were unable to swallow due to complete oesophageal obstruction and underwent combined antegrade-retrograde endoscopic dilation (CARD) within the last 10 years. The patients' demographic characteristics, clinical parameters, endoscopic therapy, adverse events, and outcomes were obtained retrospectively. Technical success was defined as effective restoration of oesophageal patency. Swallowing success was defined as either percutaneous endoscopic gastrostomy (PEG)-tube independency and/or relevant improvement of oral food intake, as assessed by the functional oral intake scale (FOIS) (>= level 3). RESULTS: The cohort consisted of six patients [five males; mean age 71 years (range, 54-74)]. All but one patient had undergone radiotherapy for head and neck or oesophageal cancer. Technical success was achieved in five out of six patients. After discharge, repeated dilations were performed in all five patients. During follow-up (median 27 mo, range, 2 115), three patients remained PEG-tube dependent. Three of four patients achieved relevant improvement of swallowing (two patients: FOIS 6, one patient: FOIS 7). One patient developed mediastinal emphysema following CARD, without a need for surgery. CONCLUSION: The CARD technique is safe and a viable alternative to high risk blind antegrade dilation in patients with complete proximal oesophageal obstruction. Although only half of the patients remained PEG-tube independent, the majority improved their ability to swallow. PMID- 26900300 TI - CD24 genetic variants contribute to overall survival in patients with gastric cancer. AB - AIM: To investigate the role of single nucleotide polymorphisms (SNPs) in CD24 gene in susceptibility and overall survival of gastric cancer (GC). METHODS: We genotyped 3 tagging SNPs of CD24-P-534 in the promoter region, P170 in the coding region of exon 2 and P1527 in the 3' untranslated region - using polymerase chain reaction-restriction fragment length polymorphism in specimens from 679 histologically-confirmed GC cases, 111 gastric atrophy (GA) cases and 976 tumor free controls. Serum immunoglobulin G antibodies to Helicobacter pylori (H. pylori) of all subjects were detected by enzyme-linked immunosorbent assay. CD24 expression was evaluated by immunohistochemistry in 131 GC specimens. Correlations between SNPs and risk of GC or GA were shown by P values and odd ratios (ORs) with 95% confidence intervals (95%CI) compared with the most common genotype of each SNP using the unconditional logistic regression model after adjusting for age, sex and H. pylori infection. Survival within each SNP group was plotted by Kaplan-Meier method and compared by log-rank test (recessive model). Hazard ratios with 95%CIs were computed by Cox regression model after adjusting for age, sex, histological type, tumor differentiation, clinical stage and post-operational chemotherapy. RESULTS: All of the three loci were in Hardy Weinberg equilibrium in the control group. Median follow-up time for the 600 GC patients included in the survival analysis was 36.2 mo (range, 2.1-66.7 mo; 95%CI: 34.3-36.5 mo). Patients with the P-534 A/A genotype had significantly shorter survival (HR = 1.38, 95%CI: 1.01-1.88, P = 0.042) than did the C/C or C/A genotype carriers after adjusting for age, sex, histological type, tumor differentiation, clinical stage and post-operational chemotherapy. This trend was more evident in patients who lived longer than 2.5 years (HR = 7.55, 95%CI: 2.16 26.32, P = 0.001). The P170 T/T genotype was associated with a shorter lifespan than the non-T/T genotypes, but not significantly so. None of the three genetic variants was found to be associated with risk of GC (including tumor stage, grade and distant metastasis) or with risk of gastric atrophy. Furthermore, no difference of CD24 expression was found among the genotypes. CONCLUSION: The P 534 site in CD24 gene affects the overall survival of gastric cancer and may serve as a prognostic marker for gastric cancer. PMID- 26900301 TI - Rare type of pancreatitis as the first presentation of anti-neutrophil cytoplasmic antibody-related vasculitis. AB - A pancreatic tumor was suspected on the abdominal ultrasound of a 72-year-old man. Abdominal computed tomography showed pancreatic enlargement as well as a diffuse, poorly enhanced area in the pancreas; endoscopic ultrasound-guided fine needle aspiration biopsy and endoscopic retrograde cholangiopancreatography failed to provide a definitive diagnosis. Based on the trend of improvement of the pancreatic enlargement, the treatment plan involved follow-up examinations. Later, he was hospitalized with an alveolar hemorrhage and rapidly progressive glomerulonephritis; he tested positive for myeloperoxidase-anti-neutrophil cytoplasmic antibody (ANCA) and was diagnosed with ANCA-related vasculitis, specifically microscopic polyangiitis. It appears that factors such as thrombus formation caused by the vasculitis in the early stages of ANCA-related vasculitis cause abnormal distribution of the pancreatic blood flow, resulting in non uniform pancreatitis. Pancreatic lesions in ANCA-related vasculitis are very rare. Only a few cases have been reported previously. Therefore, we report our case and a review of the literature. PMID- 26900302 TI - Cystic micropapillary neoplasm of peribiliary glands with concomitant perihilar cholangiocarcinoma. AB - We report a case of a 75-year-old man with cystic micropapillary neoplasm of peribiliary glands detected preoperatively by radiologic examination. Enhanced computed tomography showed a low-density mass 2.2 cm in diameter in the right hepatic hilum and a cystic lesion around the common hepatic duct. Under a diagnosis of perihilar cholangiocarcinoma, right hepatectomy with caudate lobectomy and bile duct resection were performed. Pathological examination revealed perihilar cholangiocarcinoma mainly involving the right hepatic duct. The cystic lesion was multilocular and covered by columnar lining epithelia exhibiting increased proliferative activity and p53 nuclear expression; it also contained foci of micropapillary and glandular proliferation. Therefore, the lesion was diagnosed as a cystic micropapillary neoplasm of peribiliary glands and resembled flat branch-type intraductal papillary mucinous neoplasm of the pancreas. Histological examination showed the lesion was discontinuous with the perihilar cholangiocarcinoma. Immunohistochemistry showed the cystic neoplasm was strongly positive for MUC6 and that the cholangiocarcinoma was strongly positive for MUC5AC and S100P. These results suggest these two lesions have different origins. This case warrants further study on whether this type of neoplasm is associated with concomitant cholangiocarcinoma as observed in pancreatic intraductal papillary mucinous neoplasm with concomitant pancreatic duct adenocarcinoma. PMID- 26900303 TI - Laparoscopic resection of adult colon duplication causing intussusception. AB - Gastrointestinal duplications are uncommon congenital malformations that can occur anywhere along the gastrointestinal tract. Most cases are recognized before the age of 2 years, and those encountered in adults are rare. We describe here a case of ascending colon duplication in a 20-year-old male that caused intussusception and was treated laparoscopically. Although computed tomography revealed a cystic mass filled with stool-like material, the preoperative diagnosis was a submucosal tumor of the ascending colon. We performed a laparoscopic right colectomy, and the postoperative pathological diagnosis was duplication of the ascending colon, both cystic and tubular components. We conclude that gastrointestinal duplications, although rare, should be considered in the differential diagnosis of all abdominal and submucosal cystic lesions and that laparoscopy is a preferred approach for the surgical treatment of gastrointestinal duplications. PMID- 26900304 TI - Parental involvement, child effort, and the development of immigrant boys' and girls' reading and mathematics skills: A latent difference score growth model. AB - Gender differences in elementary school performance among immigrant children have not yet been well documented. This study examined how differences in parental involvement, child effort, and family characteristics and resources contribute to immigrant boys'-and girls' academic achievement from kindergarten through 5th grade. The sample was drawn from the Early Childhood Longitudinal Study Kindergarten cohort. Using a latent score growth model, this study found that parents' involvement at home benefited boys' reading and mathematics skills throughout all early elementary school years, but did not have the same benefit for girls. For both boys and girls, child effort in reading appears to be strongly linked to better reading and mathematics skills at kindergarten and to subsequent improvement between grades. The positive associations of parental involvement and child's effort with test scores were greater during earlier years than during later years for boys, whereas there was no difference in the association over time for girls. PMID- 26900305 TI - The Dilemmas of Frontline Staff Working with the Homeless: Housing First, Discretion, and the Task Environment. AB - This paper examines staff discretion in permanent supportive housing facilities run by a nonprofit agency claiming to use a housing-first approach. Field observation, archival data, and individual and group interviews with staff and clients were examined to better understand agency processes involved in intake, sanctions, and disposal of clients to evaluate housing-first fidelity. In their day-to-day interactions with clients, frontline workers' discretion is affected by working conditions such as lack of resources and heavy workloads, as well as by demands placed on the agency by members of the its task environment. Implications for housing-first programs and homeless clients are discussed. PMID- 26900307 TI - Brachial Artery-Brachial Vein Fistula for Hemodialysis: One- or Two-Stage Procedure-A Review. AB - Purpose The purpose of the study was to investigate the patency rate of the brachial vein transposition-arteriovenous fistula [BVT-AVF] and to review the available literature regarding the comparison of the one-stage with the two-stage procedure. Methods A multiple electronic health database search was performed, aiming to identify studies on brachial vein superficialization. Case reports and series with five or less patients were excluded from the study. End points of the study were the patency rates at 12, 24, and 36 months of follow-up. The patency of the one- or two-stage BVT-AVF procedure was investigated. Results Overall, 380 BVT-AVFs were analyzed. The primary patency rate at 12 months ranged between 24 and 77%. Rate of early fistula malfunction or failure of maturation of the fistula resulting in loss of functionality ranged from 0 to 53%. Forearm edema, hematomas, wound infection, and early thrombosis were among the most common complications. Limited data were available for the comparison of patency rates between the one- and the two-stage procedure because of the absence of sufficient comparative studies. However, series with one-stage procedure presented a lower patency rate at 12 months compared to series with two stages. Conclusion Patency rates after BVT-AVF, although not excellent, has encouraging results taking into account that patients undergoing these procedures do not have an accessible superficial vein network; failure of maturation and the increased rate of early postoperative complications remain a concern. The BVT-AVF is a valuable option for creating an autologous vascular access in patients lacking adequate superficial veins. PMID- 26900308 TI - Manual Aspiration Thrombectomy in Acute Myocardial Infarction: A Clinical Experience. AB - Multiple clinical studies have failed to establish the role of routine use of thrombectomy in ST-elevation myocardial infarction (STEMI) patients. There is a paucity of data on the impact of thrombectomy in unselected STEMI patients outside clinical trials. We sought to evaluate the clinical variables and outcomes associated with the performance of thrombectomy in STEMI patients. We retrospectively examined the clinical outcomes in all STEMI patients who underwent successful percutaneous intervention (PCI) at our center. Patients were divided into two groups, one with patients who underwent conventional PCI and another with patients who had thrombus aspiration in addition to conventional PCI. We compared the baseline clinical characteristics, laboratory investigations, re-infarction rates, and all-cause mortality. Total 477 consecutive STEMI patients were identified. Overall, 29% (139) of the patients underwent conventional PCI and 71% (338) of the patients were treated with aspiration thrombectomy and PCI. In addition to the presence of thrombus, patients with nonanterior infarction, and patients with hemodynamic instability requiring intra-aortic balloon pump support were more likely to undergo thrombectomy. Thrombectomy was associated with higher enzymatic infarction (creatine kinase: 2,796 [2,575] vs. 1,716 [1,662]; p < 0.0001; CK-MB: 210.6 [156.0] vs. 142.0 [121.9], p < 0.0001). However, thrombectomy was not associated with any difference in 30 day reinfarction rate (3.3 vs. 2.9%, p = 0.83), mortality (5.0 vs. 7.2%, p = 0.35), or composite of death and 30 day reinfarction (7.7 vs. 9.4%, p = 0.55). We observed that STEMI patients with anterior infarction and hemodynamic instability were more likely to undergo thrombectomy during primary PCI. PMID- 26900306 TI - Association between Bacterial Infection and Peripheral Vascular Disease: A Review. AB - There are an increasing number of data showing a clinically important association between bacterial infection and peripheral artery disease (PAD). Bacteria suspected of being involved in PAD pathogenesis are: periodontal bacteria, gut microbiota, Helicobacter pylori, and Chlamydia pneumoniae. Infectious agents may be involved in the pathogenesis of atherosclerosis via activation of a systemic or local host immunological response to contamination of extravascular tissues or the vascular wall, respectively. A systemic immunological reaction may damage vascular walls in the course of autoimmunological cross-reactions between anti pathogen antibodies and host vascular antigens (immunological mimicry), pathogen burden mechanisms (nonspecific activation of inflammatory processes in the vascular wall), and neuroendocrine-immune cross-talk. Besides activating the inflammatory pathway, bacterial infection may trigger PAD progression or exacerbation by enhancement of platelet reactivity, by a stimulatory effect on von Willebrand factor binding, factor VIII, fibrinogen, P-selectin activation, disturbances in plasma lipids, increase in oxidative stress, and resistance to insulin. Local inflammatory host reaction and induction of atherosclerotic plaque progression and/or instability result mainly from atherosclerotic plaque colonization by microorganisms. Despite these premises, the role of bacterial infection in PAD pathogenesis should still be recognized as controversial, and randomized, controlled trials are required to evaluate the outcome of periodontal or gut bacteria modification (through diet, prebiotics, and probiotics) or eradication (using antibiotics) in hard and surrogate cardiovascular endpoints. PMID- 26900309 TI - Recipient Criteria Predictive of Graft Failure in Kidney Transplantation. AB - Several classifications systems have been developed to predict outcomes of kidney transplantation based on donor variables. This study aims to identify kidney transplant recipient variables that would predict graft outcome irrespective of donor characteristics. All U.S. kidney transplant recipients between October 25,1999 and January 1, 2007 were reviewed. Cox proportional hazards regression was used to model time until graft failure. Death-censored and nondeath-censored graft survival models were generated for recipients of live and deceased donor organs. Recipient age, gender, body mass index (BMI), presence of cardiac risk factors, peripheral vascular disease, pulmonary disease, diabetes, cerebrovascular disease, history of malignancy, hepatitis B core antibody, hepatitis C infection, dialysis status, panel-reactive antibodies (PRA), geographic region, educational level, and prior kidney transplant were evaluated in all kidney transplant recipients. Among the 88,284 adult transplant recipients the following groups had increased risk of graft failure: younger and older recipients, increasing PRA (hazard ratio [HR],1.03-1.06], increasing BMI (HR, 1.04-1.62), previous kidney transplant (HR, 1.17-1.26), dialysis at the time of transplantation (HR, 1.39-1.51), hepatitis C infection (HR, 1.41-1.63), and educational level (HR, 1.05-1.42). Predictive criteria based on recipient characteristics could guide organ allocation, risk stratification, and patient expectations in planning kidney transplantation. PMID- 26900310 TI - Common Carotid Artery Occlusion: A Single-Center Experience in 40 Cases. AB - The incidence of common carotid artery occlusion (CCAO) is approximately 3% in patients who undergo angiography for symptomatic cerebrovascular disease; however, few studies have reported on management of this condition. The objective of this article was to analyze risk factors, therapeutic options, and clinical benefits of surgical treatment at a hospital in the city of Sao Paulo, Brazil. Data were collected from medical records of 40 patients with CCAO who were treated from June 2002 to October 2013. Results were analyzed retrospectively. Most of the patients were men (63.0%), who were significantly younger than women. Most of the participants had hypertension (90.0%), and more than half had a history of smoking (52.5%). The mean number of coexisting comorbidities/risk factors was 2.9 +/- 1.0. Half of our sample had ipsilateral patent internal and external carotid artery, and 32.5% presented with an occluded internal carotid artery and a patent external artery. Patients with both an internal and an external occluded carotid artery (12.5%) were significantly older. Contralateral arteriosclerosis was observed in 65% of the patients, mainly represented by 50 to 90% stenosis. Most patients were symptomatic (67.5%), and hemiparesis was the most common symptom (55.0%) found. Most (77.5%) of the patients underwent the medical treatment; one out of three endovascular approaches failed. During the mean follow-up of 55 +/- 43 months (range, 2-136 months), 17.5% of the patients died within 4 days after surgical repair and after along 123 months of clinical follow-up. Coexisting comorbidities/risk factors were significantly associated with fatal outcomes, such as acute myocardial infarction. This study provides scientific evidences on treatment and outcomes of CCAO. PMID- 26900311 TI - Plasma Levels of Advanced Glycation End Products Are Related to the Clinical Presentation and Angiographic Severity of Symptomatic Lower Extremity Peripheral Arterial Disease. AB - Evidence implicates a role of advanced glycation end products (AGEs) in the development of atherosclerosis. The present study examined the relationship between plasma levels of AGEs and the clinical and angiographic characteristics of patients with symptomatic peripheral arterial disease (PAD). A total of 40 consecutive patients with symptomatic lower extremity PAD undergoing invasive evaluation were enrolled. Clinical history, angiographic data, and plasma levels of total AGE (tAGE), N'-carboxymethyllysine (CML), and high-sensitivity C reactive protein were obtained. In multivariate analyses, there were independent relationships noted between tAGE levels and the presence of critical limb ischemia (CLI) (r (2) = 0.195, p = 0.003), Rutherford stage (r (2) = 0.351, p < 0.001), and the average below the knee (BTK) score (r (2) = 0.119, p = 0.006). Presence of CLI (r (2) = 0.154, p = 0.012) and the Rutherford stage (r (2) = 0.194, p = 0.003) were associated with CML levels. We demonstrate a relationship between tAGE and the symptom profile of patients with PAD and an association between tAGE and infrapopliteal angiographic disease severity. Both tAGE and CML levels were related to the presence of CLI. These data suggest that AGE levels may reflect the severity of PAD and may be of importance in CLI. PMID- 26900313 TI - Laparoscopic Repair of Foramen of Winslow Hernia. AB - Foramen of Winslow hernia is a rare surgical entity with very few reported cases in literature. Preoperative diagnosis used to be difficult but with emerging computed tomography technology, diagnosing this internal abdominal hernia has become easier. We present an unusual case report of foramen of Winslow hernia in a 77-year-old patient who presented with severe abdominal pain. The patient underwent laparoscopic repair of the hernia and recovered well postoperatively. This presentation of symptoms in a 77-year-old male is unusual and laparoscopic management of foramen of Winslow hernia presents an interesting and challenging management scenario. PMID- 26900312 TI - Predictors of Peak Troponin Level in Acute Coronary Syndromes: Prior Aspirin Use and SYNTAX Score. AB - The peak troponin level has been associated with cardiovascular (CV) mortality and adverse CV events. The association of peak troponin with CV risk factors and severity and complexity of coronary artery disease remains unknown. We assessed the predictors of peak troponin in patients with acute coronary syndrome (ACS). This study aims to determine the predictors of peak troponin in ACS. Cardiac catheterization (CC) reports and electronic medical records from 2010 to 2013 were retrospectively reviewed. A total of 219 patients were eligible for the study. All major CV risk factors, comorbidities, laboratory data, CC indications, and coronary lesion characteristics were included. Univariate and multivariate regression analyses were done. On multivariate linear regression analysis, ST elevation myocardial infarction (p = 0.001, beta = 65.16) and increasing synergy between percutaneous coronary intervention with Taxus and cardiac surgery (SYNTAX) score (p = 0.002, beta = 1.15) were associated with higher peak troponin. The Pearson correlation between SYNTAX score and peak troponin was r = 0.257, p = 0.001. History of daily aspirin use was associated with lower peak troponin (p = 0.002, beta = -24.32). Prior statin use (p = 0.321, beta = -8.98) and the presence of CV risk factors were not associated with peak troponin. Coronary artery disease severity and complexity, urgency of CC, and prior aspirin use are associated with peak troponin levels in ACS. Our findings may help predict patient population with ACS who would be at a greater risk for short- and long-term CV morbidity and mortality due to elevated peak troponin. PMID- 26900314 TI - Cystic Adventitial Disease of Popliteal Artery: Case Report. AB - Cystic adventitial disease (CAD) is a rare cause of arterial stenosis. A total of 85% of cases are usually found in the popliteal artery. Men in their fourth and fifth decade are more commonly affected. If untreated the disease will progress eventually ending in occlusion of the affected vessel and limb-threatening ischemia. With this in mind an effective and long-lasting treatment is required, and here we present a case with CAD of the popliteal artery and discuss the merits of different treatment strategies. PMID- 26900315 TI - Successful Endovascular Removal of a Perforated Inferior Vena Cava Filter Complicated by a Large Retroperitoneal Hematoma: Pitfall of Catheter-Directed Thrombolysis. AB - Symptomatic caval perforation is rare complication after inferior vena cava (IVC) filter insertion. A 44-year-old woman developed back pain after the placement of retrieval IVC filter during catheter-directed thrombolysis (CDT). Her computed tomography showed a large right-sided retroperitoneal hematoma. After 2 weeks, endovascular removal of the perforated filter was successfully performed without complication. Because thrombolytic agents can accelerate bleeding caused by endovascular procedures, the bleeding rate of the IVC filter deployment during CDT might be higher than expected. PMID- 26900316 TI - Parent Programs for Reducing Adolescent's Antisocial Behavior and Substance Use: A Randomized Controlled Trial. AB - Two theoretically based parent training programs, delivered in real-world settings by the social services, were examined in this randomized controlled trial for effectiveness in reducing adolescents' antisocial behavior and substance use. Two hundred and thirty-seven (237) adolescents in ages between 12 and 18 and their parents were assigned to one of two programs or to a wait-list control condition. The programs were the nine weekly group sessions program Comet 12-18 (Swedish Parent Management Training Program) and the six weekly ParentSteps (Swedish shortened version by Strengthening Families Program 10-14). Outcome measures were antisocial behavior, substance use, and delinquency, and psychosocial dysfunction. Data based on adolescents' and parents' ratings of the adolescents' problem behavior at baseline and 6 months later were analyzed with repeated measures ANVOA, Logistic regression, and Kruskal-Wallis H test. The results showed that parents' ratings of adolescents' antisocial behaviors decreased significantly over time, but no time by group effect emerged. No program effects were found in the adolescents' self-reported antisocial behavior, delinquency, or psychosocial functioning. A threefold risk of illicit drug use was found in both intervention groups. The results suggest that neither Comet nor ParentSteps had beneficial effects on adolescent's antisocial or delinquent behavior, or on alcohol use. The only significant group difference found was a threefold risk of drug use in the intervention adolescents at follow-up, but for several reasons this finding should be interpreted with caution. Trial registration number: ISRCTN76141538. PMID- 26900318 TI - The Mediating Role of Romantic Desolation and Dating Anxiety in the Association Between Interpersonal Competence and Life Satisfaction Among Polish Young Adults. AB - This study investigates the role of romantic desolation on life satisfaction in young adulthood. Using data from a Polish sample of 330 (205 females and 125 males) young adults aged 20-30, who completed Polish versions of the Satisfaction With Life Scale, Dating Anxiety Scale, Interpersonal Competence Questionnaire Revised, and Social and Emotional Loneliness Scale for Adults-Short Form, romantic desolation (romantic loneliness and lack of a romantic partner) and dating anxiety were tested as mediators of the association between interpersonal competence and life satisfaction. Results revealed that single individuals reported lower life satisfaction and higher romantic loneliness than did partnered individuals. At the same time, no differences emerged between single and partnered individuals in dating anxiety or interpersonal competence. Structural equation modeling results showed that low interpersonal competence has an indirect effect on romantic desolation through higher levels of dating anxiety. Also, dating anxiety had an indirect effect on lower life satisfaction through increased romantic desolation. These results highlight the important role of dating anxiety and romantic desolation for explaining why low interpersonal competence is associated with diminished life satisfaction in young adults. PMID- 26900317 TI - Stress and Alcohol, Cigarette, and Marijuana Use Among Latino Adolescents in Families with Undocumented Immigrants. AB - Families in which one or more members are undocumented immigrants experience unique hardships. Yet, little is known about stress and substance use among adolescents growing up in these families. The present study examined associations between two sources of adolescent stress (i.e., low parental involvement due to contextual constraints and family economic insecurity) and lifetime alcohol, cigarette, and marijuana use among adolescents in families with undocumented members. The sample was comprised of 102 adolescents (10-18 years old) and one of his or her parents. Participants responded a survey in English or Spanish. Adolescent lifetime use of alcohol, cigarette, and marijuana was 51%, 32.4%, and 37.3%, respectively. Chi-Square analyses found no significant gender differences in lifetime substance use. Logistic regression models showed that adolescent stress due to hindered parental involvement increased the odds of both lifetime cigarette and marijuana use after controlling for gender, age, linguistic acculturation, familism, parental control, and negative peer affiliation. Being a girl increased the odds of lifetime alcohol use. Family economic stress was not associated with lifetime substance use. Results suggest that hindered parental involvement might be a stressor and a risk factor for cigarette and marijuana use among adolescents growing up in families with undocumented members. Because parents in these families are likely to be undocumented, policies that allow immigrants to apply for legal status could improve parents' working conditions and facilitate parental involvement; in turn, such policies could decrease the risk for adolescent substance use among children of Latino immigrants. PMID- 26900319 TI - Resilience of the Childhood Origins of Dutch Mothers' Gender Role Attitudes. AB - Based on qualitative analysis of 39 in depth interviews with Dutch mothers, this paper firstly explores if differences in primary socialization are relevant to an understanding of Dutch mothers' current diverse (personal) gender role attitudes. Secondly, it addresses the interplay of a mother's own gender role attitude and those of her partner and peers. The findings reveal that Dutch mothers' current diverse gender role attitudes have origins in the transmission of different mental and verbal parental, especially maternal, symbols. Egalitarian mothers often recall a strong mother-figure, the verbal persuasion of economic independence and/or particular non-traditional upbringing matters that appealed to their logic of being financially independent. The memories of traditional/adaptive mothers rather stand out for the resignation of unpaid tasks by their own mothers, and the absence of parental encouragement to consider their professional life. The findings further indicate that in childhood originated aspects of mother's personal gender role attitude continue to shape the character of mother's behavior and new social relationships. PMID- 26900320 TI - 'A confession of ignorance': deaths from old age and deciphering cause-of-death statistics in Scotland, 1855-1949. AB - A large amount of the research undertaken in an attempt to discover the reasons underlying the late nineteenth- and early twentieth-century mortality decline in Britain has relied on the statistics published by the Registrars General. The processes by which individual causes of death are recorded and then processed in order to create the statistics are not, however, well understood. In this article, the authors build on previous work to piece together a time series of causes of death for Scotland, which removes many of the discontinuities encountered in the published statistics that result from the Registrar General deciding to update the nosology, or classification system, which was being used to compile his figures. Having regrouped individual causes of death to 'smooth' the time series, the authors use the new groups to examine the changing causes of death in Scotland for selected age groups, before turning to undertake a detailed examination of mortality amongst those aged 55 or more. The authors find that when deaths from 'old age' in the latter age group are separated from other 'ill defined' causes, it becomes obvious that there was a 'rebranding' of cause of death. The authors then use individual-level data from two Scottish communities to further dissect the roles played by 'informants' and 'doctors' in this rebranding, in order to see how these roles may have altered over time and what the consequences might be for one's view of how mortality changed in Scotland between 1855 and 1949. Finally, the authors argue that their findings have important implications for some of historical demography's most prominent theories: the McKeown thesis and the theory of epidemiological transition. PMID- 26900321 TI - PCR analysis for assessment of bacterial bioburden in orthokeratology lens cases. AB - PURPOSE: To develop a PCR gel analysis method for assessing the bacterial bioburden in orthokeratology contact lens (OK) case fluid determined by culture. METHODS: A prospective study with the participation of 41 OK wearers (20 girls, 21 boys) was performed. The mean OK-wearing experience was 3.5+/-1.9 years. PCR was used to assess the bacterial bioburden (colony-forming units per milliliter) of OK after removal and soaking in the storage case for 6 h. The signal intensity of the PCR bands was analyzed after grayscale image transformation. The difference (cPCR-d) and ratio (cPCR-r) between a PCR signal and its background were used as two standardized indices of PCR signals. The association between the two indices of the PCR signals and the bacterial bioburden determined by culture were analyzed with Pearson's correlation coefficient (r) and receiver operating characteristic (ROC) plots. RESULTS: At least one microbe was isolated from the OK lens case from 38 of the 41 subjects. Both cPCR-d and cPCR-r showed strong correlations with the bacterial bioburden (r>0.7, p<0.0001). ROC analysis enabled good determination of the cutoff values for the two PCR indices with acceptable sensitivity and specificity (78-89%) to assess the degree of bacterial contamination. CONCLUSIONS: The high microbial contamination rate of the OK lens cases revealed the general inappropriate lens care by OK wearers. PCR analysis provides an alternative and rapid method for assessing the bacterial bioburden of OK lens cases, and these results should serve as a warning to OK wearers to follow appropriate lens care procedures to prevent infection. PMID- 26900322 TI - CFI-rs7356506 polymorphisms associated with Vogt-Koyanagi-Harada syndrome. AB - PURPOSE: Complement factor I (CFI) plays an important role in complement activation pathways and is known to affect the development of uveitis. The present study was performed to investigate the existence of an association between CFI genetic polymorphisms and Vogt-Koyanagi-Harada (VKH) syndrome. METHODS: A total of 100 patients diagnosed with VKH syndrome and 300 healthy controls were recruited for the study. Two milliliters of peripheral blood were collected in a sterile anticoagulative tube. CFI-rs7356506 polymorphisms were genotyped using Sequenom MassARRAY technology. Allele and genotype frequencies were compared between patients and controls using a chi(2) test. The analyses were stratified for recurrent status, complicated cataract status, and steroid sensitive status. RESULTS: No significant association was found between CFI rs7356506 polymorphisms and VKH syndrome. However, patients with recurrent VKH syndrome had lower frequencies of the G allele and GG homozygosity in CFI rs7356506 when compared to the controls (p=0.016, odds ratio [OR]=0.429, 95% confidence interval [CI]=0.212-0.871; p=0.014, OR=0.364, 95% CI=0.158-0.837, respectively). Furthermore, there were significant decreases in the frequencies of the G allele and GG homozygosity in CFI-rs7356506 in patients with VKH syndrome with complicated cataract compared to the controls (p<0.001, OR=0.357, 95% CI=0.197-0.648; p<0.001, OR=0.273, 95% CI=0.135-0.551, respectively). Nevertheless, no significant association with patients with VKH syndrome in steroid-sensitive statuses was detected for CFI-rs7356506 polymorphisms. CONCLUSIONS: Our results indicate that CFI polymorphisms are not significantly associated with VKH syndrome; nevertheless, we identified a trend for the association of CFI-7356506 with VKH syndrome that depends on the recurrent status and the complicated cataract status but not on the steroid-sensitive status. PMID- 26900323 TI - EPHA2 MUTATIONS CONTRIBUTE TO CONGENITAL CATARACT THROUGH DIVERSE MECHANISMS. AB - PURPOSE: Congenital cataract is a leading cause of childhood blindness. Mutations in the EPHA2 gene are one of the causes of inherited congenital cataract. The EPHA2 gene encodes a membrane-bound tyrosine kinase receptor and is highly expressed in epithelial cells, including in the ocular lens. Signaling through the EPHA2 receptor plays a pivotal role in epithelial cell homeostasis. The aim of this study was to determine the effect of congenital cataract causing mutations in the EPHA2 gene on the encoded protein in epithelial cells. METHODS: The effect of five disease-causing mutations, p.P584L (c.1751C>T), p.T940I (c.2819C>T), p.D942fsXC71 (c.2826-9G>A), p.A959T (c.2875G>A), and p.V972GfsX39 (c.2915_2916delTG), on localization of the protein was examined in two in vitro epithelial cell culture systems: Madin-Darby Canine Kidney (MDCK) and human colorectal adenocarcinoma (Caco-2) epithelial cells. Myc-tagged mutant constructs were generated by polymerase chain reaction (PCR)-based mutagenesis. The Myc tagged wild-type construct was used as a control. The Myc-tagged wild-type and mutant proteins were ectopically expressed and detected by immunofluorescence labeling. RESULTS: Two of the mutations, p.T940I and p.D942fsXC71, located within the cytoplasmic sterile-alpha-motif (SAM) domain of EPHA2, led to mis localization of the protein to the perinuclear space and co-localization with the cis-golgi apparatus, indicating sub-organellar/cellular retention of the mutant proteins. The mutant proteins carrying the remaining three mutations, similar to the wild-type EPHA2, localized to the cell membrane. CONCLUSIONS: Mis localization of two of the mutant proteins in epithelial cells suggests that some disease-causing mutations in EPHA2 likely affect lens epithelial cell homeostasis and contribute to cataract. This study suggests that mutations in EPHA2 contribute to congenital cataract through diverse mechanisms. PMID- 26900324 TI - RNA-seq analysis of impact of PNN on gene expression and alternative splicing in corneal epithelial cells. AB - PURPOSE: The specialized corneal epithelium requires differentiated properties, specific for its role at the anterior surface of the eye. Thus, tight maintenance of the differentiated qualities of the corneal epithelial is essential. Pinin (PNN) is an exon junction component (EJC) that has dramatic implications for corneal epithelial cell differentiation and may act as a stabilizer of the corneal epithelial cell phenotype. Our studies revealed that PNN is involved in transcriptional repression complexes and spliceosomal complexes, placing PNN at the fulcrum between chromatin and mRNA splicing. Transcriptome analysis of PNN knockdown cells revealed clear and reproducible alterations in transcript profiles and splicing patterns of a subset of genes that would significantly impact the epithelial cell phenotype. We further investigated PNN's role in the regulation of gene expression and alternative splicing (AS) in a corneal epithelial context. METHODS: Human corneal epithelial (HCET) cells that carry the doxycycline-inducible PNN-knockdown shRNA vector were used to perform RNA-seq to determine differential gene expression and differential AS events. RESULTS: Multiple genes and AS events were identified as differentially expressed between PNN-knockdown and control cells. Genes upregulated by PNN knockdown included a large proportion of genes that are associated with enhanced cell migration and ECM remodeling processes, such as MMPs, ADAMs, HAS2, LAMA3, CXCRs, and UNC5C. Genes downregulated in response to PNN depletion included IGFBP5, FGD3, FGFR2, PAX6, RARG, and SOX10. AS events in PNN-knockdown cells compared to control cells were also more likely to be detected, and upregulated. In particular, 60% of exon skipping events, detected in only one condition, were detected in PNN-knockdown cells and of the shared exon-skipping events, 92% of those differentially expressed were more frequent in the PNN knockdown. CONCLUSIONS: These data suggest that lowering of PNN levels in epithelial cells results in dramatic transformation in the number and composition of splicing variants and that PNN plays a crucial role in the selection of which RNA isoforms differentiating cells produce. Many of the genes affected by PNN knockdown are known to affect the epithelial phenotype. This window into the complexity of RNA splicing in the corneal epithelium implies that PNN exerts broad influence over the regulation and maintenance of the epithelial cell phenotype. PMID- 26900325 TI - Effects of blue light on the circadian system and eye physiology. AB - Light-emitting diodes (LEDs) have been used to provide illumination in industrial and commercial environments. LEDs are also used in TVs, computers, smart phones, and tablets. Although the light emitted by most LEDs appears white, LEDs have peak emission in the blue light range (400-490 nm). The accumulating experimental evidence has indicated that exposure to blue light can affect many physiologic functions, and it can be used to treat circadian and sleep dysfunctions. However, blue light can also induce photoreceptor damage. Thus, it is important to consider the spectral output of LED-based light sources to minimize the danger that may be associated with blue light exposure. In this review, we summarize the current knowledge of the effects of blue light on the regulation of physiologic functions and the possible effects of blue light exposure on ocular health. PMID- 26900326 TI - A novel H395R mutation in MKKS/BBS6 causes retinitis pigmentosa and polydactyly without other findings of Bardet-Biedl or McKusick-Kaufman syndrome. AB - PURPOSE: To identify the causative mutation in two siblings from a consanguineous family in India with retinitis pigmentosa (RP) and polydactyly without other findings of Bardet-Biedl syndrome (BBS). We also performed functional characterization of the mutant protein to explore its role in this limited form of BBS. METHODS: The siblings underwent a thorough ophthalmological examination, including retinal optical coherence tomography (OCT) imaging, and an extensive physical examination with abdominal ultrasonography to characterize the disease phenotype. Next-generation sequencing (NGS) using a panel targeting retinal degeneration genes was performed on genomic DNA samples from the siblings and parents. Upon identification of the causative mutation, functional characterization was accomplished by performing protein-protein interaction studies in human embryonic kidney (HEK-293T) and human adult retinal pigmented epithelium (ARPE-19) cells. RESULTS: The two siblings showed signs of RP and polydactyly. The patients did not have truncal obesity, renal anomalies, hydrometrocolpos, congenital heart disease, or overt cognitive defects. NGS identified a homozygous c.1184A>G mutation in the MKKS/BBS6 gene in both patients resulting in a p.H395R substitution in the MKKS/BBS6 protein. This mutant protein decreased the interaction of MKKS/BBS6 with BBS12 but did so to a different extent in the HEK-293T versus ARPE-19 cells. Nonetheless, the effect of the H395R variant on disrupting interactions with BBS12 was not as profound as other reported MKKS/BBS6 mutations associated with syndromic RP. CONCLUSIONS: We identified a novel H395R substitution in MKKS/BBS6 that results in a unique phenotype of only RP and polydactyly. Our observations reaffirm the notion that mutations in MKKS/BBS6 cause phenotypic heterogeneity and do not always result in classic MKKS or BBS findings. PMID- 26900328 TI - TNF-alpha mediates choroidal neovascularization by upregulating VEGF expression in RPE through ROS-dependent beta-catenin activation. AB - PURPOSE: Inflammation, oxidative stress, and angiogenesis have been proposed to interact in age-related macular degeneration. It has been postulated that external stimuli that cause oxidative stress can increase production of vascular endothelial growth factor (VEGF) in retinal pigment epithelial (RPE) cells. In this study, we tested the hypothesis that the inflammatory cytokine, tumor necrosis factor alpha (TNF-alpha), contributed to choroidal neovascularization (CNV) by upregulating VEGF in RPE through intracellular reactive oxygen species (ROS)-dependent signaling and sought to understand the mechanisms involved. METHODS: In a murine laser-induced CNV model, 7 days after laser treatment and intravitreal neutralizing mouse TNF-alpha antibody or isotype immunoglobulin G (IgG) control, the following measurements were made: 1) TNF-alpha protein and VEGF protein in RPE/choroids with western blot, 2) CNV volume in RPE/choroidal flatmounts, and 3) semiquantification of oxidized phospholipids stained with E06 antibody within CNV with immunohistochemistry (IHC). In cultured human RPE cells treated with TNF-alpha or PBS control, 1) ROS generation was measured using the 2',7'-dichlorodihydrofluorescein diacetate (DCFDA) fluorescence assay, and 2) NOX4 protein and VEGF protein or mRNA were measured with western blot or quantitative real-time PCR in cells pretreated with apocynin or nicotinamide adenine dinucleotide phosphate-oxidase (NADPH) inhibitor, VAS 2870, or transfected with p22phox siRNA, and each was compared to its appropriate control. Western blots of phosphorylated p65 (p-p65), total p65 and beta-actin, and quantitative real-time PCR of VEGF mRNA were measured in human RPE cells treated with TNF-alpha and pretreatment with the nuclear factor kappa B inhibitor, Bay 11 7082 or control. Western blots of beta-catenin, VEGF, and p22phox and coimmunoprecipitation of beta-catenin and T-cell transcriptional factor were performed in human RPE cells treated with TNF-alpha following pretreatment with beta-catenin transcriptional inhibitors, XAV939 or JW67, or transfection with p22phox siRNA and compared to appropriate controls. RESULTS: Compared to the non lasered control, TNF-alpha and VEGF protein were increased in the RPE/choroids in a murine laser-induced CNV model (p<0.05). An intravitreal neutralizing antibody to mouse TNF-alpha reduced CNV volume, and VEGF protein in the RPE/choroids (p<0.01) and oxidized phospholipids within CNV compared to IgG control (p<0.05). In cultured RPE cells and compared to controls, TNF-alpha induced ROS generation and increased activation of NOX4, an isoform of NADPH oxidase; both were prevented by pretreatment with the apocynin or VAS2870 or knockdown of p22phox, a subunit of NADPH oxidase. TNF-alpha treatment increased VEGF expression (p<0.001) and the formation of a transcriptional complex of beta-catenin and T-cell transcriptional factor; both were prevented by pretreatment with apocynin or knockdown of p22phox. Inhibition of beta-catenin by XAV939, but not the nuclear factor kappa B inhibitor, Bay 11-7082, prevented TNF-alpha-induced VEGF upregulation. CONCLUSIONS: Our results support the thinking that TNF-alpha contributes to CNV by upregulating VEGF production in RPE cells through ROS dependent activation of beta-catenin signaling. These results provide mechanisms of crosstalk between inflammatory mediator, TNF-alpha, and ROS in RPE cells. PMID- 26900327 TI - Scleral fibroblast response to experimental glaucoma in mice. AB - PURPOSE: To study the detailed cellular and molecular changes in the mouse sclera subjected to experimental glaucoma. METHODS: Three strains of mice underwent experimental bead-injection glaucoma and were euthanized at 3 days and 1, 3, and 6 weeks. Scleral protein expression was analyzed with liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) using (16)O/(18)O labeling for quantification in 1- and 6-week tissues. Sclera protein samples were also analyzed with immunoblotting with specific antibodies to selected proteins. The proportion of proliferating scleral fibroblasts was quantified with Ki67 and 4',6 diamidino-2-phenylindole (DAPI) labeling, and selected proteins were studied with immunohistochemistry. RESULTS: Proteomic analysis showed increases in molecules involved in integrin-linked kinase signaling and actin cytoskeleton signaling pathways at 1 and 6 weeks after experimental glaucoma. The peripapillary scleral region had more fibroblasts than equatorial sclera (p=0.001, n=217, multivariable regression models). There was a sixfold increase in proliferating fibroblasts in the experimental glaucoma sclera at 1 week and a threefold rise at 3 and 6 weeks (p=0.0005, univariate regression). Immunoblots confirmed increases for myosin, spectrin, and actinin at 1 week after glaucoma. Thrombospondin-1 (TSP-1), HINT1, vimentin, actinin, and alpha-smooth muscle actin were increased according to immunohistochemistry. CONCLUSIONS: Scleral fibroblasts in experimental mouse glaucoma show increases in actin cytoskeleton and integrin-related signaling, increases in cell division, and features compatible with myofibroblast transition. PMID- 26900329 TI - How can the results of Health Technology Assessment (HTA) evaluations applied to vaccinations be communicated to decision-makers and stakeholders? The ISPOR Rome Chapter Project. AB - HTA is considered the most comprehensive and transparent method of supporting decision-makers in their choices in Public Health. HTA on vaccines is being performed by many experts. However, they often present their studies to colleagues, but not to decisionmakers, who should be the main target and current users. It is therefore crucial to improve the transfer of scientific data to decision- makers and all stakeholders. The aims of the present project are: 1) to set up a team of experts to collect economic evaluations and HTA studies on vaccines and assess their actual use in decision-making processes; 2) to constitute regional working groups in order to identify the critical aspects of the communication process and identify the most appropriate method of data transfer. Systematic reviews of economic evaluations and HTA on vaccines and their actual use in decision-making will be used to draw up the basic documents for discussion by the 3 regional working boards. The working groups will discuss the current scientific evidence and communication methods and will try to implement a model of technology assessment with well-defined and objective criteria, in order to better fit pharmaco-economic and HTA methods to the field of vaccinations. Improving the transfer of HTA results to stakeholders, particularly decision-makers, will enable decisions to be taken on the basis of scientific evidence, and appropriate, sustainable actions to be undertaken. PMID- 26900330 TI - A Health Technology Assessment: laparoscopy versus colpoceliotomy. AB - INTRODUCTION: The objective of this paper is the comparison between two different technologies used for the removal of a uterine myoma, a frequent benign tumor: the standard technology currently used, laparoscopy, and an innovative one, colpoceliotomy. It was considered relevant to evaluate the real and the potential effects of the two technologies implementation and, in addition, the consequences that the introduction or exclusion of the innovative technology would have for both the National Health System (NHS) and the entire community. METHODS: The comparison between these two different technologies, the standard and the innovative one, was conducted using a Health Technology Assessment (HTA). In particular, in order to analyse their differences, a multi-dimensional approach was considered: effectiveness, costs and budget impact analysis data were collected, applying different instruments, such as the Activity Based Costing methodology (ABC), the Cost-Effectiveness Analysis (CEA) and the Budget Impact Analysis (BIA). Organisational, equity and social impact were also evaluated. RESULTS: The results showed that the introduction of colpoceliotomy would provide significant economic savings to the Regional and National Health Service; in particular, a saving of ? 453.27 for each surgical procedure. DISCUSSION: The introduction of the innovative technology, colpoceliotomy, could be considered a valuable tool; one offering many advantages related to less invasiveness and a shorter surgical procedure than the standard technology currently used (laparoscopy). PMID- 26900331 TI - Impact of different scoring algorithms applied to multiple-mark survey items on outcome assessment: an in-field study on health-related knowledge. AB - INTRODUCTION: Health-related knowledge is often assessed through multiple-choice tests. Among the different types of formats, researchers may opt to use multiple mark items, i.e. with more than one correct answer. Although multiple-mark items have long been used in the academic setting - sometimes with scant or inconclusive results - little is known about the implementation of this format in research on in-field health education and promotion. METHODS: A study population of secondary school students completed a survey on nutrition-related knowledge, followed by a single- lecture intervention. Answers were scored by means of eight different scoring algorithms and analyzed from the perspective of classical test theory. The same survey was re-administered to a sample of the students in order to evaluate the short-term change in their knowledge. RESULTS: In all, 286 questionnaires were analyzed. Partial scoring algorithms displayed better psychometric characteristics than the dichotomous rule. In particular, the algorithm proposed by Ripkey and the balanced rule showed greater internal consistency and relative efficiency in scoring multiple-mark items. A penalizing algorithm in which the proportion of marked distracters was subtracted from that of marked correct answers was the only one that highlighted a significant difference in performance between natives and immigrants, probably owing to its slightly better discriminatory ability. This algorithm was also associated with the largest effect size in the pre-/post-intervention score change. DISCUSSION: The choice of an appropriate rule for scoring multiple- mark items in research on health education and promotion should consider not only the psychometric properties of single algorithms but also the study aims and outcomes, since scoring rules differ in terms of biasness, reliability, difficulty, sensitivity to guessing and discrimination. PMID- 26900332 TI - The relationship between physical activity and quality of life in prisoners: a pilot study. AB - INTRODUCTION: Imprisoned people have usually a poor health status in comparison with the general population. The aim is to investigate a possible association between the quality of life and physical activity level in male inmates. METHODS: A cross-sectional pilot study was carried out between 2010 and 2011. A questionnaire contained SF12 and International Physical Activity Questionnaire was administered. Mental Component Score (MCS) and Physical Component Score (PCS) were computed. The physical activity level was measured using Metabolic Equivalents score (MET). RESULTS: 121 inmates entered the survey. MCS is directly correlated to MET of physical activity (beta = 0.23; P = 0.03) and negatively to BMI variations (beta = -0.24; P = 0.02) and smoking status (beta = -0.24; P = 0.02). DISCUSSION: This pilot study suggests to improve the investigation to support the promotion of physical activity programs in Italian prisons in order to improve inmates QoL and allow a better social integration at the end of detention. PMID- 26900333 TI - Susceptibility of multidrug resistant clinical pathogens to a chlorhexidine formulation. AB - Multidrug resistant pathogens are a widespread problem in the hospital setting especially on intensive care units (ICU). This study evaluated the susceptibility of clinical isolates of gramnegative extensively drug resistant organisms (XDR), methicillinresistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococcus (VRE) to a proprietary chlorhexidine digluconate (CHG) formulation used in one brand of CHG-impregnated cloths. Ten isolates each of XDR Pseudomonas aeruginosa, XDR Acinetobacter baumannii, XDR Klebsiella pneumoniae, XDR Escherichia coli, MRSA, and vancomycin-resistant Enterococcus faecium from our hospital were tested. All isolates were susceptible to the proprietary CHG formulation (0.5%, 1%, 2%), with 99% to 100% suppression of growth at the earliest time point in time kill assays (1 minute for gram-positive and 15 seconds for gram-negative organisms). Minimum inhibitory concentrations ranged from 1 : 4096 to 1 : 65536 for MRSA, 1 : 1024 to 1 : 2048 for VRE, 1 : 2048 to 1 : 4096 for XDR E. coli, 1 : 512 to 1 : 2048 for XDR A. baumannii, 1 : 512 to 1 : 1024 for XDR P. aeruginosa, and 1 : 512 to 1 : 1024 for XDR K. pneumoniae. Cloths impregnated with this CHG formulation provide effective protection against colonization and infection by many pathogens. This study provides in vitro evidence that the proprietary CHG formulation used in one brand of CHG impregnated cloths is effective against XDR gram-negative organisms, MRSA, and VRE. PMID- 26900334 TI - Determinants of failure to thrive (FTT) among infants aged 6-24 months: a case control study. AB - INTRODUCTION: Failure to thrive (FTT) in children is one of the most important health issues around the world, especially in developing countries. Lack of success in identifying and controlling this health problem may lead to dangerous health consequences for children. The aim of this research was to explore the risk factors for this health problem in infants under two years of age in Urmia, Northwest of Iran. METHODS: This case-control study was carried out on 445 infants of 6 to 24 months (180 as cases, and 265 as controls) in Urmia, Northwest of Iran, during 2013. The study samples were selected from six health centers, using the purposeful sampling method. To collect data, a questionnaire including items regarding sociodemographics of the children's families, and demographic and nutrition-related variables of infants was utilized. To analysis data and determine the real effect of the aforementioned factors on growth status of infants, a chi-square test and logistic regression analysis were applied. RESULTS: The regression analysis revealed that education level of infants' mothers [AOR = 1.421, 95% CI (1.172, 1.724)], duration of breastfeeding [AOR = 1.859, 95% CI (1.212, 2.852)], birth weight of infants [AOR = 2.777, 95% CI (1.276, 7.166)], family's monthly income [AOR = 1.492, 95% CI (1.117, 2.230)] were correlated with FTT as significant risk factors (P < 0.05). Birth order of infants [AOR = .741, 95% CI ( .573- .958)], however, appeared to be a protective factor for child growth (P < 0.05). DISCUSSION: The findings of the study may help health care providers in designing and implementing appropriate interventions for improving children's health. In addition, taking into account the importance of healthy growth of children, educating mothers/caretakers would seem beneficial in preventing dangerous diseases in children. PMID- 26900335 TI - Nitrates in drinking water: relation with intensive livestock production. AB - INTRODUCTION: An excess of nitrates causes environmental pollution in receiving water bodies and health risk for human, if contaminated water is source of drinking water. The directive 91/676/ CEE [1] aims to reduce the nitrogen pressure in Europe from agriculture sources and identifies the livestock population as one of the predominant sources of surplus of nutrients that could be released in water and air. Directive is concerned about cattle, sheep, pigs and poultry and their territorial loads, but it does not deal with fish farms. Fish farms effluents may contain pollutants affecting ecosystem water quality. METHODS: On the basis of multivariate statistical analysis, this paper aims to establish what types of farming affect the presence of nitrates in drinking water in the province of Cuneo, Piedmont, Italy. In this regard, we have used data from official sources on nitrates in drinking water and data Arvet database, concerning the presence of intensive farming in the considered area. For model selection we have employed automatic variable selection algorithm. RESULTS AND DISCUSSION: We have identified fish farms as a major source of nitrogen released into the environment, while pollution from sheep and poultry has appeared negligible. We would like to emphasize the need to include in the "Nitrate Vulnerable Zones" (as defined in Directive 91/676/CEE [1]), all areas where there are intensive farming of fish with open-system type of water use. Besides, aquaculture open-system should be equipped with adequate downstream system of filtering for removing nitrates in the wastewater. PMID- 26900336 TI - Occurrence of Acrylamide in breakfast cereals and biscuits available in Italy. AB - INTRODUCTION: Acrylamide, produced during thermal processing of carbohydrate-rich foods, is classified as "probably carcinogenic to humans" by the International Agency for Research on Cancer. OBJECTIVE: The aim of this study was to determine acrylamide levels in biscuits and breakfast cereals considering the widespread use of these products for all ages. METHOD: Acrylamide determination was carried out in 56 samples by HPLC-UV technique. RESULTS AND DISCUSSION: The results showed a considerable variability in the contents of acrylamide in the samples analysed, most likely due to differences in industrial processing and ingredients. The percentages of contaminated samples tested were very high (95.5% of the biscuits and 75% of the breakfast cereals) with a wide range of contamination: from 30 MUg/kg to 940 MUg/kg. Our results showed that 22.7% of biscuits and 33% of breakfast cereals exceeded the indicative values recommended by EC 2013/647 set at 500 MUg/kg and 200-400 MUg/kg (according to the composition) respectively. CONCLUSIONS: Our findings suggest concern about the risk for human health. PMID- 26900337 TI - Prevalence of acute alcohol intoxication in Borgo Trento Hospital Emergency Department (Verona). AB - INTRODUCTION: Alcohol is an important factor weighting towards global disease burden, premature death and Disability-Adjusted Life Years. This study examines the burden imposed on the Borgo Trento Verona Hospital Emergency Department (ED) Italy by patients with Acute Alcohol Intoxication (AAI). METHODS: A 6-year retrospective study was performed by reviewing medical records in all patients (>= 16 years old) diagnosed with AAI. Clinical criteria for inclusion in the sample followed those defined in the "Alcohol Intoxication Symptoms" section of DSM-IV-TR. Ambiguous cases presenting traumas potentially related to AAI were confirmed positive using a Blood Alcohol Level (BAL) test before inclusion in the sample. Socio-demographic data, case history, timing of admission/discharge and outcome were collected for each patient. RESULTS: One thousand five hundred forty seven patients (males:females = 6.6:1) were included in the study. With regard to marital status, the crude rate within the sample shows that single and married subjects have a significantly higher prevalence (p < 0.01). When demographic data of residents was taken into consideration, divorced/separated and single categories were significantly more represented (p < 0.05). The admissions appeared fairly constant throughout the week with a higher prevalence of patients aged between 25-55 years, and a significant peak of the youngest age class on weekends. Higher rates of admission were recorded during the late afternoon and night. The triage code of admission appeared uniformly distributed along the week, with the highest prevalence of green code (67.7%), followed by yellow one (25.8%). The analysis of clinical symptoms and BAL highlights that moderate clinical severity concerns almost 50%, and clinically critical severity the 6.6% of cases of access. Admissions rates of foreign patients resulted to be 3 times higher compared to those of natives when adjusted to demographic data. DISCUSSION: Social disadvantages such as foreign provenance and social difficulties as unemployment, low money intake, perception of loneliness, and dysfunction in family life were frequently identified in the sample. An exception was found within the youngest age group, where the AAI are mostly related to alcohol abuse during social outings over the weekend. EDs play a crucial role in helping patients with AAI, but prevention of alcohol abuse though implementation of social and sanitary health policies on all ages (but especially among the youngest) is essential. PMID- 26900338 TI - A very rare case of uterine PEComa HMB45 negative: primitive or relapse? AB - Perivascular epithelioid cell tumors (PEComas) represent a rare group of tumours with uncertain malignancy potential exhibiting an immunophenotype characterized by actin and Human Melanoma Black 45 (HMB45) immunoreactivity. Our case concerns about a rare malignant uterine perivascular epithelioid cell tumour diagnosed in a patient underwent to subtotal hysterectomy with unclear diagnosis, 12 years before. Histological diagnosis after colposcopic exam with biopsy revealed a perivascular epithelioid cell tumor, with immunohistochemical profle negative for HMB45. Negativity for HMB45, already described in literature, could be due to important cellular modifcations of tumoral tissue. In our case, tumour was unresectable, progression of disease occurred during medical treatment and the patient died after 6 months. Lack of information about frst surgery doesn't allow to surely categorized the tumor as primitive or relapse. Further studies are necessary to understand some immunohistochemical anomaly like negativity for HMB45. PMID- 26900339 TI - Efficient and automatic methods for flexible regression on spatiotemporal data, with applications to groundwater monitoring. AB - Fitting statistical models to spatiotemporal data requires finding the right balance between imposing smoothness and following the data. In the context of P splines, we propose a Bayesian framework for choosing the smoothing parameter, which allows the construction of fully automatic data-driven methods for fitting flexible models to spatiotemporal data. An implementation, which is highly computationally efficient and exploits the sparsity of the design and penalty matrices, is proposed. The findings are illustrated using a simulation study and two examples, all concerned with the modelling of contaminants in groundwater. This suggests that the proposed strategy is more stable that competing methods based on the use of criteria such as generalised cross-validation and Akaike's Information Criterion. (c) 2015 The Authors. Environmetrics Published by John Wiley Sons Ltd. PMID- 26900340 TI - Surface modification of a polyethylene film for anticoagulant and anti-microbial catheter. AB - A functional anticoagulant and anti-bacterial coating for polyethylene (PE) films is described. The stepwise preparation of this nanocomposite surface coating involves O2 plasma etching of PE film, carbodiimide coupling of cysteamine to the etched PE film, binding of Ag to sulfhydryl groups of cysteamine, and assembly of heparin capped AgNPs on the PE film. The nanocomposite film and its components were characterized by 1H-nuclear magnetic resonance spectroscopy, attenuated total reflectance-Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and field emission-scanning electron microscopy. The resulting PE films demonstrate anticoagulant activity using a hemoglobin whole blood clotting assay, and anti-bacterial activity against Bacillus cereus 3551 (Gram-positive) and Escherichia coli BL21 (Gram-negative) bacteria. The hydrophilicity of the heparin coated PE was determined by contact angle measurements; and the stability of the nanocomposite film, with respect to Ag leaching, was assessed by atomic absorption spectroscopy. PMID- 26900341 TI - Prospects for improving the LHC W boson mass measurement with forward muons. AB - Measurements of the W boson mass are planned by the ATLAS and CMS experiments, but for the time being, these may be unable to compete with the current world average precision of 15 MeV, due to uncertainties in the PDFs. We discuss the potential of a measurement by the LHCb experiment based on the charged lepton transverse momentum [Formula: see text] spectrum in [Formula: see text] decays. The unique forward acceptance of LHCb means that the PDF uncertainties would be anti-correlated with those of [Formula: see text] based measurements by ATLAS and CMS. We compute an average of ATLAS, CMS and LHCb measurements of [Formula: see text] from the [Formula: see text] distribution. Considering PDF uncertainties, this average is a factor of 1.3 more precise than an average of ATLAS and CMS alone. Despite the relatively low rate of W production in LHCb, we estimate that with the Run-II dataset, a measurement could be performed with sufficient experimental precision to exploit this anti-correlation in PDF uncertainties. The modelling of the lepton-pair transverse momentum distribution in the neutral current Drell-Yan process could be a limiting factor of this measurement and will deserve further studies. PMID- 26900342 TI - NLO+NLL squark and gluino production cross sections with threshold-improved parton distributions. AB - We present updated predictions for the cross sections for pair production of squarks and gluinos at the LHC Run II. First of all, we update the calculations based on NLO+NLL partonic cross sections by using the NNPDF3.0NLO global analysis. This study includes a full characterization of theoretical uncertainties from higher orders, PDFs and the strong coupling. Then we explore the implications for this calculation of the recent NNPDF3.0 PDFs with NLO+NLL threshold resummation. We find that the shift in the results induced by the threshold-improved PDFs is within the total theory uncertainty band of the calculation based on NLO PDFs. However, we also observe that the central values of the NLO+NLL cross sections are modified both in a qualitative and a quantitative way, illustrating the relevance and impact of using threshold improved PDFs together with resummed partonic cross sections. The updated NLO+NLL cross sections based on NNPDF3.0NLO are publicly available in the NLL-fast format, and should be an important ingredient for the interpretation of the searches for supersymmetric particles at Run II. PMID- 26900344 TI - Techniques for the treatment of IR divergences in decay processes at NLO and application to the top-quark decay. AB - We present the extension of two general algorithms for the treatment of infrared singularities arising in electroweak corrections to decay processes at next-to leading order: the dipole subtraction formalism and the one-cutoff slicing method. The former is extended to the case of decay kinematics which has not been considered in the literature so far. The latter is generalised to production and decay processes with more than two charged particles, where new "surface" terms arise. Arbitrary patterns of massive and massless external particles are considered, including the treatment of infrared singularities in dimensional or mass regularisation. As an application of the two techniques we present the calculation of the next-to-leading order QCD and electroweak corrections to the top-quark decay width including all off-shell and decay effects of intermediate [Formula: see text] bosons. The result, e.g., represents a building block of a future calculation of NLO electroweak effects to off-shell top-quark pair ([Formula: see text]) production. Moreover, this calculation can serve as the first step towards an event generator for top-quark decays at next-to-leading order accuracy, which can be used to attach top-quark decays to complicated many particle top-quark processes, such as for [Formula: see text] or [Formula: see text]. PMID- 26900345 TI - The effects of wealth, occupation, and immigration on epidemic mortality from selected infectious diseases and epidemics in Holyoke township, Massachusetts, 1850-1912. AB - BACKGROUND: Previous research suggests individual-level socioeconomic circumstances and resources may be especially salient influences on mortality within the broader context of social, economic, and environmental factors affecting urban 19th century mortality. OBJECTIVE: We sought to test individual level socioeconomic effects on mortality from infectious and often epidemic diseases in the context of an emerging New England industrial mill town. METHOD: We analyze mortality data from comprehensive death records and a sample of death records linked to census data, for an emergent industrial New England town, to analyze infectious mortality and model socioeconomic effects using Poisson rate regression. RESULTS: Despite our expectations that individual resources might be especially salient in the harsh mortality setting of a crowded, rapidly growing, emergent, industrial mill town with high levels of impoverishment, infectious mortality was not significantly lowered by individual socio-economic status or resources. PMID- 26900346 TI - Transgenic plants as a sustainable, terrestrial source of fish oils. AB - 1An alternative, sustainable source of omega-3 long chain polyunsaturated fatty acids is widely recognized as desirable, helping to reduce pressure on current sources (wild capture fisheries) and providing a de novo source of these health beneficial fatty acids. This review will consider the efforts and progress to develop transgenic plants as terrestrial sources of omega-3 fish oils, focusing on recent developments and the possible explanations for advances in the field. We also consider the utility of such a source for use in aquaculture, since this industry is the major consumer of oceanic supplies of omega-3 fish oils. Given the importance of the aquaculture industry in meeting global requirements for healthy foodstuffs, an alternative source of omega-3 fish oils represents a potentially significant breakthrough for this production system. Transgenic Camelina seeds engineered to accumulate the omega-3 fatty acids EPA and DHA, represent a sustainable alternative to fish oils. PMID- 26900347 TI - MicroRNA-410-5p as a potential serum biomarker for the diagnosis of prostate cancer. AB - BACKGROUND: Prostate cancer (PCa) remains to be a diagnostic challenge due to its variable presentation and the lack of reliable diagnosis tool. MicroRNAs (miRNAs) regulate gene in extensive range of pathophysiologic processes. Plasma miRNAs are ideal biomarkers in heart failure, diabetes and other disease. However, using circulating miRNAs as biomarkers for the diagnosis of PCa is still unknown. METHODS: 149 PCa patients, 57 healthy controls, and 121 non-cancer patients (benign prostatic hyperplasia and other urinary diseases) were enrolled in this study. The reverse transcription of miRNA and SYBR-Green-based double standards curve miRNA quantitative polymerase chain reactions (qPCR) were used to evaluate the dysregulated miR-410-5p. Receiver operator characteristic (ROC) curve analysis was used to evaluate the diagnostic accuracy of miR-410-5p identified as the alternative biomarker. RESULTS: Circulating miRNA-410-5p (miR-410-5p) level was significantly higher in the PCa patients than in healthy controls or non cancer patients. ROC curve analysis showed that plasma miR-410-5p was a specific diagnostic biomarker of PCa with an area under curve(AUC) of 0.8097 (95 % confidence interval, 0.7371-0.8823; P < 0.001). CONCLUSIONS: The serum miR-410-5p level is a potential biomarker for the diagnosis of PCa. PMID- 26900348 TI - Tumor suppressor genes and their underlying interactions in paclitaxel resistance in cancer therapy. AB - OBJECTIVES: Paclitaxel (PTX) is frequently used in the clinical treatment of solid tumors. But the PTX-resistance is a great obstacle in cancer treatment. Exploration of the mechanisms of drug resistance suggests that tumor suppressor genes (TSGs) play a key role in the response of chemotherapeutic drugs. TSGs, a set of genes that are often inactivated in cancers, can regulate various biological processes. In this study, an overview of the contribution of TSGs to PTX resistance and their underlying relationship in cancers are reported by using GeneMANIA, a web-based tool for gene/protein function prediction. METHODS: Using PubMed online database and Google web site, the terms "paclitaxel resistance" or "taxol resistance" or "drug resistance" or "chemotherapy resistance", and "cancer" or "carcinoma", and "tumor suppressor genes" or "TSGs" or "negative regulated protein" or "antioncogenes" were searched and analyzed. GeneMANIA data base was used to predict gene/protein interactions and functions. RESULTS: We identified 22 TSGs involved in PTX resistance, including BRCA1, TP53, PTEN, APC, CDKN1A, CDKN2A, HIN-1, RASSF1, YAP, ING4, PLK2, FBW7, BLU, LZTS1, REST, FADD, PDCD4, TGFBI, ING1, Bax, PinX1 and hEx. The TSGs were found to have direct and indirect relationships with each other, and thus they could contribute to PTX resistance as a group. The varied expression status and regulation function of the TSGs on cell cycle in different cancers might play an important role in PTX resistance. CONCLUSION: A further understanding of the roles of tumor suppressor genes in drug resistance is an important step to overcome chemotherapy tolerance. Tumor suppressor gene therapy targets the altered genes and signaling pathways and can be a new strategy to reverse chemotherapy resistance. PMID- 26900349 TI - Diagnostic utility of serum and pleural fluid carcinoembryonic antigen, and cytokeratin 19 fragments in patients with effusion from nonsmall cell lung cancer. AB - AIMS: To assess the diagnostic value of CEA and CYFRA 21-1 (cytokeratin 19 fragments) in serum and pleural fluid in non small cell lung cancer with malignant pleural effusion (MPE). SETTINGS AND DESIGN: Two subsets of patients were recruited with lymphocytic exudative effusion, one subset constituted diagnosed patients of NSCLC with malignant pleural effusion and the other subset of constituted with Tubercular pleural effusion. MATERIALS AND METHODS: CYFRA 21 1 and CEA levels were measured using Electrochemilumiscence Immunoassay (ECLIA). The test principle used the Sandwich method. For both the tests, results are determined via a calibration curve which is instrument specifically generated by 2 - point calibration and a master curve provided via reagent barcode. STATISTICAL ANALYSIS USED: All data are expressed as means +/- SD and percentage. All the parametric variables were analysed by student-t test where as non parametric variables were compared by Mann-Whitney U-test Statistical significance was accepted for P values < 0.05. Software used were SPSS 11.5, and MS excel 2007. In order to compare the performance of the tumor markers, receiver operating characteristic (ROC) curves were constructed and compared with area under the curve (AUC). The threshold for each marker was selected based on the best diagnostic efficacy having achieved equilibrium between sensitivity and specificity. RESULTS: In cases serum CYFRA21-1 levels had mean value of 34.1 +/- 29.9 with a range of 1.6-128.3 where as in controls serum CYFRA21-1 levels had mean value of 1.9 +/- 1.0 with a range of 0.5-4.7. In cases serum CEA levels had mean value of 24.9 +/- 47.3 with a range of 1.0, 267.9 where as in controls serum CEA levels had mean value of 1.9 +/- 1.4 with a range of 0.2-6.8. The difference in the means of serum CYFRA 21-l (P = 0.000) and CEA (P = 0.046) were statistically significant. In cases pleural fluid CYFRA21-1 levels had mean value of 160.1 +/- 177.1 with a range of 5.4-517.2 where as in controls pleural fluid CYFRA21-1 levels had mean value of 15.9 +/- 5.7 with a range of 7.2-29.6. In cases CEA pleural fluid levels had mean value of 89.8 +/- 207.4 with a range of 1.0-861.2 where as in controls CEA levels had mean value of 2.5 +/- 2.3 with a range of 1-8.9. The difference in the means of CYERA 21-1 (P = 0.001) between cases and controls is statistically significant. CONCLUSIONS: CYFRA21-1 (serum - pleural fluid) is a sensitive marker for NSCLC with sensitivity of 96.7%, highest of any combination [Serum (CYFRA 21-1 - CEA). CEA (Serum + Pleural Fluid), Pleural Fluid (CYFRA 21-1 + CEA)] and specificity of 77.8%. Levels of CYFRA21-l (serum + pleural fluid) are increased in malignant pleural effusion, so it is better to be used in suspicious malignant pleural effusion showing negative cytology, particularly in the absence of a visible tumor and or unsuitability for invasive procedure. PMID- 26900350 TI - Incidence of venous thromboembolism in France: a retrospective analysis of a national insurance claims database. AB - BACKGROUND: Data estimating the annual incidence of venous thromboembolism (VTE) in France, taking into account both hospital and community settings, are very lacking. This study aimed to estimate the annual incidence of VTE (pulmonary embolism (PE) and deep vein thrombosis (DVT)) in France in 2011 in "real world" population. METHODS: This was a longitudinal insurance claims study of the incidence of VTE in France over 2 years (2010 and 2011). The data analysis was performed using the EGB (Echantillon Generaliste des Beneficiaires) database, a randomly selected sample of the French national insurance database (CNAMTS) which covers 77 % of the population. All adult patients experiencing a VTE event during the study period were analysed. Recurrence rate of VTE and all-cause mortality rate were also estimated over a 12-month follow-up period. RESULTS: The estimated annual incidence of VTE in France was 184.0 per 100 000 subjects, corresponding to a total of 119 670 events countrywide. The estimated incidence of DVT and PE were respectively 119.8 and 64.2 per 100 000 subjects. Annual recurrence of VTE was reported in 5.5 % (n = 99) patients, with a significantly higher recurrence rate in patients with PE than those with DVT (p = 0.02). Overall, 6.2 % (n = 112) of patients had died over the 12-month follow-up (respectively 10.2 and 7.7 % of patients with DVT and PE). DISCUSSION: To our knowledge, this analysis is the first to estimate the annual incidence of VTE in France using exhaustive data from the EGB database. This has allowed the incidence of DVT in the community to be documented, which to date has not been characterised. Previous studies in France have been limited to the hospital setting and have yielded incidence rates comparable to ours. CONCLUSIONS: This analysis is the first to estimate the annual incidence of VTE in France using exhaustive data from the EGB database. This study showed that the incidence and the burden of the disease remains elevated. PMID- 26900352 TI - Tissue composition effect on dose distribution in neutron brachytherapy/neutron capture therapy. AB - AIM: The aim of this study is to assess the effect of the compositions of various soft tissues and tissue-equivalent materials on dose distribution in neutron brachytherapy/neutron capture therapy. BACKGROUND: Neutron brachytherapy and neutron capture therapy are two common radiotherapy modalities. MATERIALS AND METHODS: Dose distributions were calculated around a low dose rate (252)Cf source located in a spherical phantom with radius of 20.0 cm using the MCNPX code for seven soft tissues and three tissue-equivalent materials. Relative total dose rate, relative neutron dose rate, total dose rate, and neutron dose rate were calculated for each material. These values were determined at various radial distances ranging from 0.3 to 15.0 cm from the source. RESULTS: Among the soft tissues and tissue-equivalent materials studied, adipose tissue and plexiglass demonstrated the greatest differences for total dose rate compared to 9-component soft tissue. The difference in dose rate with respect to 9-component soft tissue varied with compositions of the materials and the radial distance from the source. Furthermore, the total dose rate in water was different from that in 9 component soft tissue. CONCLUSION: Taking the same composition for various soft tissues and tissue-equivalent media can lead to error in treatment planning in neutron brachytherapy/neutron capture therapy. Since the International Commission on Radiation Units and Measurements (ICRU) recommends that the total dosimetric uncertainty in dose delivery in radiotherapy should be within +/-5%, the compositions of various soft tissues and tissue-equivalent materials should be considered in dose calculation and treatment planning in neutron brachytherapy/neutron capture therapy. PMID- 26900351 TI - Chordoma in children: Case-report and review of literature. AB - We report an exceptional case of a very late local failure in a 9-year-old boy presenting with a chordoma of the cranio-cervical junction. The child was initially treated with a combination of surgical resection followed by high dose photon-proton radiation therapy. This aggressive therapy allowed a 9-year remission with minimal side-effects. Unfortunately, he subsequently presented with a local failure managed with a second full-dose course of protons. The child died one year later from local bleeding of unclear etiology. PMID- 26900353 TI - Evaluation of hypothetical (153)Gd source for use in brachytherapy. AB - AIM: The purpose of this work is to evaluate the dosimetric parameters of a hypothetical (153)Gd source for use in brachytherapy and comparison of the dosimetric parameters with those of (192)Ir and (125)I sources. MATERIALS AND METHODS: Dose rate constant, the radial dose function and the two dimensional (2D) anisotropy function data for the hypothetical (153)Gd source were obtained by simulation of the source using MCNPX code and then were compared with the corresponding data reported by Enger et al. A comprehensive comparison between this hypothetical source and a (192)Ir source with similar geometry and a (125)I source was performed as well. RESULTS: Excellent agreement was shown between the results of the two studies. Dose rate constant values for the hypothetical (153)Gd, (192)Ir, (125)I sources are 1.173 cGyh(-1) U(-1), 1.044 cGyh(-1) U(-1), 0.925 cGyh(-1) U(-1), respectively. Radial dose function for the hypothetical (153)Gd source has an increasing trend, while (192)Ir has more uniform and (125)I has more rapidly falling off radial dose functions. 2D anisotropy functions for these three sources indicate that, except at 0.5 cm distance, (192)Ir and (125)I have more isotropic trends as compared to the (153)Gd source. CONCLUSION: A more uniform radial dose function, and 2D anisotropy functions with more isotropy, a much higher specific activity are advantages of (192)Ir source over (153)Gd. However, a longer half-life of (153)Gd source compared to the other two sources, and lower energy of the source with respect to (192)Ir are advantages of using (153)Gd in brachytherapy versus (192)Ir source. PMID- 26900354 TI - Unintended irradiation of internal mammary chain - Is that enough? AB - AIM: To evaluate the unintentional coverage of the internal mammary chain (IMC) with tangential fields irradiation to the breast, and its relation with the type of surgery employed. BACKGROUND: The dose distribution in regions adjacent to the treatment targets (mammary gland or chest wall), with incidental irradiation of the IMC, could translate into clinical benefit, due to the proximity of these regions. MATERIALS AND METHODS: One hundred and twelve consecutive conformal radiotherapy plans were correlating the average dose to the IMC with the type of surgery employed, the extent of disease and the irradiation techniques. RESULTS: The mean doses to IMC after modified radical mastectomy (MRM), modified radical mastectomy with immediate reconstruction (MRM + R), and breast conservative surgery (BCS) were 30.34 Gy, 30.26 Gy, and 18.67 Gy, respectively. Significant differences were identified between patients who underwent MRM or MRM + R over BCS (p = 0.01 and 0.003, respectively), but not between MRM and MRM + R (p = 0.88). Mean doses to IMC were greater in patients with T3-T4 tumors when compared with more initial stages (<=T2) (p = 0.0096). The lymph node involvement also correlated with higher average doses to IMC (node positive: 26.1 Gy * node negative: 17.8 Gy, p = 0.0017). CONCLUSIONS: The moderate dose level to the IMC in the unintentional irradiation scenario seems to be insufficient to treat the subclinical disease, although it could have an impact in patients undergoing mastectomy. PMID- 26900355 TI - Muscle-invasive bladder cancer treated with TURB followed by concomitant boost with small reduction of radiotherapy field with or without of chemotherapy. AB - AIM: To evaluate the clinical outcome and toxicity of the treatment of muscle invasive bladder cancer (MIBC) that combined transurethral resection of bladder tumor (TURB) with "concomitant boost" radiotherapy delivered over a shortened overall treatment time of 5 weeks, with or without concurrent chemotherapy. BACKGROUND: Local control of MIBC by bladder-sparing approach is unsatisfactory. In order to improve the effectiveness of radiotherapy, we have designed a protocol that combines TURB with a non-conventionally fractionated radiotherapy "concomitant boost". MATERIALS AND METHODS: Between 2004 and 2010, 73 patients with MIBC cT2-4aN0M0, were treated with "concomitant boost" radiotherapy. The whole bladder with a 2-3 cm margin was irradiated with fractions of 1.8 Gy to a dose of 45 Gy, with a "concomitant boost" to the bladder with 1-1.5 cm margin, during the last two weeks of treatment, as a second fraction of 1.5 Gy, to a total dose of 60 Gy. Radiochemotherapy using mostly cisplatin was delivered in 42/73(58%) patients, 31/73(42%) patients received radiotherapy alone. RESULTS: Acute genitourinary toxicity of G3 was scored in 3/73(4%) patients. Late gastrointestinal toxicity higher than G2 and genitourinary higher than G3 were not reported. Complete remission was achieved in 48/73(66%), partial remission in 17/73(23%), and stabilization disease in 8/73(11%) patients. Three- and five-year overall, disease specific and invasive locoregional disease-free survival rates were 65% and 52%, 70% and 59%, 52% and 43%, respectively. CONCLUSIONS: An organ sparing approach using TURB followed by radio(chemo)therapy with "concomitant boost" in patients with MIBC allows to obtain long-term survival with acceptable toxicity. PMID- 26900356 TI - A novel dynamic field-matching technique for treatment of patients with para aortic node-positive cervical cancer: Clinical experience. AB - AIM: To report outcomes for patients with para-aortic lymph node positive cervical cancer treated with a dynamic field-matching technique. BACKGROUND: PET staging of cervical cancer has increased identification of patients with para aortic lymph node metastasis. IMRT enables dose escalation in this area, but matching IMRT fields with traditional whole pelvis fields presents a challenge. MATERIALS AND METHODS: From 2003 to 2012, 20 patients with cervical cancer and para-aortic lymph node metastasis were treated utilizing the dynamic field matching technique. As opposed to single-isocenter half-beam junction techniques, this technique employs wedge-shaped dose junctions for the abutment of fields. We reviewed the records of all patients who completed treatment with the technique and abstracted treatment, toxicity, and disease-related outcome data for analysis. RESULTS: Median prescribed dose to the whole pelvis field was 45 Gy and para-aortic IMRT field 50.4 Gy. All but 3 patients underwent HDR (13 pts) or LDR (4 pts) brachytherapy. All patients developed lower GI toxicity; 10 grade 1, 9 grade 2, and 1 grade 4 (enterovaginal fistula). Median DFS was 12.4 months with 1 and 2-year DFS 60.0% and 38.1%. One-year OS was 83.7% and 2-year OS, 64.4%. A total of 10 patients developed recurrence; none occurred at the matched junction. CONCLUSIONS: The dynamic field-matching technique provides a means for joining conventional whole pelvis fields and para-aortic IMRT fields that substantially reduces dose deviations at the junction due to field mismatch. Treatment with the dynamic matching technique is simple, effective, and tolerated with no apparent increase in toxicity. PMID- 26900357 TI - Safe bunker designing for the 18 MV Varian 2100 Clinac: a comparison between Monte Carlo simulation based upon data and new protocol recommendations. AB - AIM: The aim of this study was to compare two bunkers designed by only protocols recommendations and Monte Carlo (MC) based upon data derived for an 18 MV Varian 2100Clinac accelerator. BACKGROUND: High energy radiation therapy is associated with fast and thermal photoneutrons. Adequate shielding against the contaminant neutron has been recommended by IAEA and NCRP new protocols. MATERIALS AND METHODS: The latest protocols released by the IAEA (safety report No. 47) and NCRP report No. 151 were used for the bunker designing calculations. MC method based upon data was also derived. Two bunkers using protocols and MC upon data were designed and discussed. RESULTS: From designed door's thickness, the door designed by the MC simulation and Wu-McGinley analytical method was closer in both BPE and lead thickness. In the case of the primary and secondary barriers, MC simulation resulted in 440.11 mm for the ordinary concrete, total concrete thickness of 1709 mm was required. Calculating the same parameters value with the recommended analytical methods resulted in 1762 mm for the required thickness using 445 mm as recommended by TVL for the concrete. Additionally, for the secondary barrier the thickness of 752.05 mm was obtained. CONCLUSION: Our results showed MC simulation and the followed protocols recommendations in dose calculation are in good agreement in the radiation contamination dose calculation. Difference between the two analytical and MC simulation methods revealed that the application of only one method for the bunker design may lead to underestimation or overestimation in dose and shielding calculations. PMID- 26900358 TI - Analyzing the performance of ArcCHECK diode array detector for VMAT plan. AB - AIM: The aim of this study is to evaluate performance of ArcCHECK diode array detector for the volumetric modulated arc therapy (VMAT) patient specific quality assurance (QA). VMAT patient specific QA results were correlated with ion chamber measurement. Dose response of the ArcCHECK detector was studied. BACKGROUND: VMAT delivery technique improves the dose distribution. It is complex in nature and requires proper QA before its clinical implementation. ArcCHECK is a novel three dimensional dosimetry system. MATERIALS AND METHODS: Twelve retrospective VMAT plans were calculated on ArcCHECK phantom. Point dose and dose map were measured simultaneously with ion chamber (IC-15) and ArcCHECK diode array detector, respectively. These measurements were compared with their respective TPS calculated values. RESULTS: The ion chamber measurements are in good agreement with TPS calculated doses. Mean difference between them is 0.50% with standard deviation of 0.51%. Concordance correlation coefficient (CCC) obtained for ion chamber measurements is 0.9996. These results demonstrate a strong correlation between the absolute dose predicted by our TPS and the measured dose. The CCC between ArcCHECK doses and TPS predictions on the CAX was found to be 0.9978. In gamma analysis of dose map, the mean passing rate was 98.53% for 3% dose difference and 3 mm distance to agreement. CONCLUSIONS: The VMAT patient specific QA with an ion chamber and ArcCHECK phantom are consistent with the TPS calculated dose. Statistically good agreement was observed between ArcCHECK measured and TPS calculated. Hence, it can be used for routine VMAT QA. PMID- 26900359 TI - Use of planar kV vs. CBCT in evaluation of setup errors in oesophagus carcinoma radiotherapy. AB - AIM: The aim of this study is to evaluate differences in terms of the setup errors observed using kV planar image compared to CBCT for oesophageal cancer patients. BACKGROUND: Planar kV images are quick to acquire but only allow the observation of bony structures. CBCT allows the evaluation of soft tissues, which includes the oesophagus (and tumour) and OAR, giving a more accurate verification of the positioning. MATERIALS AND METHODS: All patients were imaged with both techniques between January 2012 and March 2014 were included in the study (16 patients, 212 kV images and 116 CBCT images). Differences between the setup errors observed on the two images modalities were studied. A correlation study between TNM staging, tumour location and immobilization systems with setup errors was also done. Finally, the calculation of systematic and random errors allowed to determine the CTV-PTV margin. RESULTS: A significant discrepancy (p < 0.05) between the setup errors observed with kV and CBCT was observed in the lateral direction. No statistical correlation was found between setup errors and tumour location, immobilization system or TNM staging. The CTV-PTV margin was smaller with CBCT in the vertical (0.6 cm vs. 0.9 cm) and longitudinal (0.7 cm vs. 1 cm) directions and smaller with kV for the lateral directions (0.8 cm vs. 0.9 cm). CONCLUSIONS: The chosen modality influences the setup error observed which will influence the correction applied. Allowing a better observation of the volumes of interest, CBCT should be the modality of choice in this pathology. The CTV-PTV margins could be shrunk if CBCT is used. PMID- 26900360 TI - A surface energy spectral study on the bone heterogeneity and beam obliquity using the flattened and unflattened photon beams. AB - AIM: Using flattened and unflattened photon beams, this study investigated the spectral variations of surface photon energy and energy fluence in the bone heterogeneity and beam obliquity. BACKGROUND: Surface dose enhancement is a dosimetric concern when using unflattened photon beam in radiotherapy. It is because the unflattened photon beam contains more low-energy photons which are removed by the flattening filter of the flattened photon beam. MATERIALS AND METHODS: We used a water and bone heterogeneity phantom to study the distributions of energy, energy fluence and mean energy of the 6 MV flattened and unflattened photon beams (field size = 10 cm * 10 cm) produced by a Varian TrueBEAM linear accelerator. These elements were calculated at the phantom surfaces using Monte Carlo simulations. The photon energy and energy fluence calculations were repeated with the beam angle turned from 0 degrees to 15 degrees , 30 degrees and 45 degrees in the water and bone phantom. RESULTS: Spectral results at the phantom surfaces showed that the unflattened photon beams contained more photons concentrated mainly in the low-energy range (0-2 MeV) than the flattened beams associated with a flattening filter. With a bone layer of 1 cm under the phantom surface and within the build-up region of the 6 MV photon beam, it is found that both the flattened and unflattened beams had slightly less photons in the energy range <0.4 MeV compared to the water phantom. This shows that the presence of the bone decreased the low-energy photon backscatters to the phantom surface. When both the flattened and unflattened photon beams were rotated from 0 degrees to 45 degrees , the number of photon and mean photon energy increased. This indicates that both photon beams became more hardened or penetrate when the beam angle increased. In the presence of bone, the mean energies of both photon beams increased. This is due to the absorption of low energy photons by the bone, resulting in more beam hardening. CONCLUSIONS: This study explores the spectral relationships of surface photon energy and energy fluence with bone heterogeneity and beam obliquity for the flattened and unflattened photon beams. The photon spectral information is important in studies on the patient's surface dose enhancement using unflattened photon beams in radiotherapy. PMID- 26900361 TI - Tension pneumocephalus secondary to osteoradionecrosis of the clivus. AB - We report the case of a 36 year-old man with relapsing undifferentiated nasopharyngeal carcinoma treated with a re-irradiation Cyberknife, who subsequently developed tension pneumocephalus due to a cerebrospinal fluid leakage located at the clivus. The fistula was caused by osteonecrosis of the skull base secondary to the tumor invasion and to the sequelae of the radiotherapy. An endoscopic endonasal technique was used in order to repair the defect, with a peduncolated nasoseptal flap harvested to perform the skull base reconstruction. In this paper, we discuss the importance of identifying this possible complication related to radiotherapy in the management of neoplasm along the skull base; moreover, the role of endoscopy in the diagnosis and treatment of skull base fistulas is also described and commented. PMID- 26900362 TI - Vemurafenib and concomitant stereotactic radiation for the treatment of melanoma with spinal metastases: A case report. AB - A 56-year-old man with BRAFV600E melanoma and spinal metastases treated with vemurafenib and stereotactic radiation showed a partial response without neurological, skin or mucosal toxicity, 8 months after completion of this combination. This case suggests that stereotactic radiation spares normal tissues and might be safer than conventional fractionated radiation with vemurafenib. PMID- 26900363 TI - Toxic epidermal necrolysis associated with radiotherapy and phenytoin in a patient with non-Hodking's lymphoma: A case report. AB - Toxic epidermal necrolysis (TEN) is a disease which is characterized by fever and desquamation of the skin and mucosal membranes. It is usually related with drugs, especially aromatic anticonvulsants which are recognized as the most common cause of this disorder. Cranial irradiation may act as a precipitating factor along with anticonvulsants for the development of TEN. We report a 28-year-old patient with central nervous system (CNS) relapsed non-Hodgkin lymphoma (NHL) who developed TEN after cranial radiotherapy and concurrent phenytoin treatment. PMID- 26900364 TI - Metachronous medulloblastoma and glioblastoma: Implications for clinical and technical aspects of re-irradiation. AB - A seven-year-old male underwent surgical resection and chemoradiation for average risk medulloblastoma; twelve years later, the presence of a necrotic and infiltrative mass in the same area and invading the brainstem prompted a subtotal resection. Pathology was indicative of glioblastoma. He was then treated with concurrent temozolomide and using biologically effective dose calculations for gross residual tumor tissue in the brainstem as well as brainstem tolerance, a radiotherapy dose of 3750 cGy was chosen, fractionated in twice-daily fractions of 125 cGy each. The gross tumor volume was expanded with a 5 mm margin to the planning target volume, which was also judiciously subtracted from the normal brainstem. He completed his radiotherapy course with subsequent imaging free of residual tumor and continued adjuvant temozolomide and remains under follow-up surveillance. This case underscores the rarity of metachronous medulloblastoma and glioblastoma, of which only five known cases heretofore have been described. We discuss the technicalities of radiotherapy planning in this patient, including common hurdles for radiation oncologists in similar patients. PMID- 26900365 TI - Corrigendum to "Uroncor consensus statement: Management of biochemical recurrence after radical radiotherapy for prostate cancer: From biochemical failure to castration resistance". [Rep. Pract. Oncol. Radiother. 20 (2015) 259-272]. AB - [This corrects the article DOI: 10.1016/j.rpor.2015.04.003.]. PMID- 26900367 TI - Genetic Testing in Epileptic Encephalopathy: Rosetta Stone or Just an Expensive Rock? PMID- 26900366 TI - Effective Disinfectants for Coccidioides immitis and C. posadasii. AB - The lack of published data on effective disinfectants and contact times for use on the fungal pathogens Coccidioides immitis and C. posadasii prompted the authors to investigate the fungicidal activity of three commonly used laboratory disinfectants on arthroconidia harvested from C. immitis strain 2009. They tested the ability of 10% bleach, 70% ethanol, and Vesphene(r) IIse to inactivate 107 arthroconidia in an aqueous suspension within 1, 2, 5, 10, or 20 minutes of contact time. Both 10% bleach and 70% ethanol provided a 7-log10 reduction in arthroconidia in less than 1 minute, with no growth observed at any of the tested time points. Vesphene(r) IIse was less effective, providing a 6-log10 reduction in arthroconidia after 5 minutes, but was unable to completely inactivate all of the arthroconidia, even after 20 minutes of contact time. PMID- 26900368 TI - Connecting the Dots? Linking Anatomy, Connectivity, and Physiology in Epilepsy. PMID- 26900369 TI - Finding the Missing Pieces: The Microdeletion Burden in GGE. PMID- 26900370 TI - Generic Substitution of AEDs: Is it Time to Put This Issue to Rest? PMID- 26900371 TI - Inspecting Resecting: Examining 20-Year Trends in Epilepsy Surgery. PMID- 26900372 TI - Imaging Brain Inflammation: If We Can See It, Maybe We Can Treat It. PMID- 26900373 TI - Perampanel: Another Choice for Patients With Idiopathic Generalized Epilepsy Who Have Tonic-Clonic Seizures. PMID- 26900374 TI - Synaptic Sweet Talk: How Do Perineuronal Nets Contribute to Epileptogenesis and Neuroplasticity? PMID- 26900375 TI - Epileptogenesis: More Than Just the Latent Period. PMID- 26900376 TI - Breathe Easy: Modifying Mitochondrial Respiration to Treat Seizures. PMID- 26900377 TI - Criminal Minds: Cav3.2 Channels Are the Culprits, but NMDAR Are the Co Conspirators. PMID- 26900378 TI - Microglial TLR9: Guardians of Homeostatic Hippocampal Neurogenesis. PMID- 26900379 TI - Fingerprints of Interictal Spikes: Can Imprints Deliver a Verdict on Their Role in Epilepsy? PMID- 26900380 TI - Locus Heterogeneity in Epilepsy of Infancy with Migrating Focal Seizures. PMID- 26900381 TI - Attitudes Toward Epilepsy Genetics Testing Among Adult and Pediatric Epileptologists-Results of a Q-PULSE Survey. PMID- 26900383 TI - Commentary on SE Guidelines. PMID- 26900384 TI - Integrating Primary Care and Behavioral Health: A Nurse Practitioner's Perspective. AB - Health equity for individuals with serious mental illness (SMI) requires collaborative partnerships between primary care and behavioral health organizations. This paper presents the experiences and perspectives of a nurse practitioner in a large-scale pilot program to integrate primary care and behavioral health between an FQHC and a community mental health center, both serving predominantly Asian immigrant populations. This paper discusses lessons learned through program implementation and provides insights on developing a truly integrated system involving equal and full cooperation across disciplines to provide quality and holistic care for patients with SMI. Implications for clinical practice and policy are discussed. PMID- 26900382 TI - Evidence-Based Guideline: Treatment of Convulsive Status Epilepticus in Children and Adults: Report of the Guideline Committee of the American Epilepsy Society. AB - CONTEXT: The optimal pharmacologic treatment for early convulsive status epilepticus is unclear. OBJECTIVE: To analyze efficacy, tolerability and safety data for anticonvulsant treatment of children and adults with convulsive status epilepticus and use this analysis to develop an evidence-based treatment algorithm. DATA SOURCES: Structured literature review using MEDLINE, Embase, Current Contents, and Cochrane library supplemented with article reference lists. STUDY SELECTION: Randomized controlled trials of anticonvulsant treatment for seizures lasting longer than 5 minutes. DATA EXTRACTION: Individual studies were rated using predefined criteria and these results were used to form recommendations, conclusions, and an evidence-based treatment algorithm. RESULTS: A total of 38 randomized controlled trials were identified, rated and contributed to the assessment. Only four trials were considered to have class I evidence of efficacy. Two studies were rated as class II and the remaining 32 were judged to have class III evidence. In adults with convulsive status epilepticus, intramuscular midazolam, intravenous lorazepam, intravenous diazepam and intravenous phenobarbital are established as efficacious as initial therapy (Level A). Intramuscular midazolam has superior effectiveness compared to intravenous lorazepam in adults with convulsive status epilepticus without established intravenous access (Level A). In children, intravenous lorazepam and intravenous diazepam are established as efficacious at stopping seizures lasting at least 5 minutes (Level A) while rectal diazepam, intramuscular midazolam, intranasal midazolam, and buccal midazolam are probably effective (Level B). No significant difference in effectiveness has been demonstrated between intravenous lorazepam and intravenous diazepam in adults or children with convulsive status epilepticus (Level A). Respiratory and cardiac symptoms are the most commonly encountered treatment-emergent adverse events associated with intravenous anticonvulsant drug administration in adults with convulsive status epilepticus (Level A). The rate of respiratory depression in patients with convulsive status epilepticus treated with benzodiazepines is lower than in patients with convulsive status epilepticus treated with placebo indicating that respiratory problems are an important consequence of untreated convulsive status epilepticus (Level A). When both are available, fosphenytoin is preferred over phenytoin based on tolerability but phenytoin is an acceptable alternative (Level A). In adults, compared to the first therapy, the second therapy is less effective while the third therapy is substantially less effective (Level A). In children, the second therapy appears less effective and there are no data about third therapy efficacy (Level C). The evidence was synthesized into a treatment algorithm. CONCLUSIONS: Despite the paucity of well-designed randomized controlled trials, practical conclusions and an integrated treatment algorithm for the treatment of convulsive status epilepticus across the age spectrum (infants through adults) can be constructed. Multicenter, multinational efforts are needed to design, conduct and analyze additional randomized controlled trials that can answer the many outstanding clinically relevant questions identified in this guideline. PMID- 26900385 TI - iqLearn: Interactive Q-Learning in R. AB - Chronic illness treatment strategies must adapt to the evolving health status of the patient receiving treatment. Data-driven dynamic treatment regimes can offer guidance for clinicians and intervention scientists on how to treat patients over time in order to bring about the most favorable clinical outcome on average. Methods for estimating optimal dynamic treatment regimes, such as Q-learning, typically require modeling nonsmooth, nonmonotone transformations of data. Thus, building well-fitting models can be challenging and in some cases may result in a poor estimate of the optimal treatment regime. Interactive Q-learning (IQ learning) is an alternative to Q-learning that only requires modeling smooth, monotone transformations of the data. The R package iqLearn provides functions for implementing both the IQ-learning and Q-learning algorithms. We demonstrate how to estimate a two-stage optimal treatment policy with iqLearn using a generated data set bmiData which mimics a two-stage randomized body mass index reduction trial with binary treatments at each stage. PMID- 26900387 TI - Ion mobility mass spectrometry enhances low-abundance species detection in untargeted lipidomics. AB - We describe a simple method for the detection of low intensity lipid signals in complex tissue samples, based on a combination of liquid chromatography/mass spectrometry and ion mobility mass spectrometry. The method relies on visual and software-assisted analysis of overlapped mobilograms (diagrams of mass-to-charge ratio, m/z, vs drift time, DT) and was successfully applied in untargeted lipidomics analyses of mouse brain tissue to detect relatively small variations in a scarce class of phospholipids (N-acyl phosphatidylethanolamines) generated during neural tissue damage, against a background of hundreds of lipid species. Standard analytical tools, including Principal Component Analysis, failed to detect such changes. PMID- 26900386 TI - Oral L-citrulline supplementation enhances cycling time trial performance in healthy trained men: Double-blind randomized placebo-controlled 2-way crossover study. AB - BACKGROUND: Many human studies report that nitric oxide (NO) improves sport performance. This is because NO is a potential modulator of blood flow, muscle energy metabolism, and mitochondrial respiration during exercise. L-Citrulline is an amino acid present in the body and is a potent endogenous precursor of L arginine, which is a substrate for NO synthase. Here, we investigated the effect of oral L-citrulline supplementation on cycling time trial performance in humans. METHODS: A double-blind randomized placebo-controlled 2-way crossover study was employed. Twenty-two trained males consumed 2.4 g/day of L-citrulline or placebo orally for 7 days. On Day 8 they took 2.4 g of L-citrulline or placebo 1 h before a 4-km cycling time trial. Time taken to complete the 4 km cycle, along with power output/VO2 ratio (PO/VO2), plasma nitrite and nitrate (NOx) and amino acid levels, and visual analog scale (VAS) scores, was evaluated. RESULTS: L Citrulline supplementation significantly increased plasma L-arginine levels and reduced completion time by 1.5 % (p < 0.05) compared with placebo. Moreover, L citrulline significantly improved subjective feelings of muscle fatigue and concentration immediately after exercise. CONCLUSIONS: Oral L-citrulline supplementation reduced the time take to complete a cycle ergometer exercise trial. TRIAL REGISTRATION: Current Controlled Trials UMIN000014278. PMID- 26900388 TI - Changes in serum fatty acid and lipoprotein subclass concentrations from prepuberty to adulthood and during aging. AB - Concentrations in serum were determined for 18 fatty acids (FAs) and 21 lipoprotein main and subclasses by chromatographic analyses and the average size was calculated for very low density (VLDL), low density (LDL) and high density (HDL) particles. 283 ethnic Norwegian children and adults from the rural Fjord region of Western Norway were compared with the objectives to reveal patterns and gender differences during the development from prepuberty to adulthood and during aging in adults. Both genders showed a large increase in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from child to adult. Males, but not females, show a significant increase in most C16-C18 FAs from prepuberty to adulthood. These changes in males correlate to a pattern of increased concentrations of triglycerides, VLDL and LDL particles, especially the atherogenic subclasses of small and very small LDL particles. Furthermore, concentrations of medium, large and very large HDL particles decrease, while concentration of very small HDL particles increase leading to reduced average size of HDL particles. Females only showed significant increase in concentrations of small and very small LDL particles, very small HDL particles and apolipoprotein B. While EPA and DHA continued to increase during aging in women, no validated model for connecting age to FA profile was obtained for men. Women showed significant increase in concentrations of all subclasses of LDL particles during aging, while men exhibited a more complex pattern with increase also in apolipoprotein A1 and HDL particles. PMID- 26900389 TI - Random access with adaptive packet aggregation in LTE/LTE-A. AB - While random access presents a promising solution for efficient uplink channel access, the preamble collision rate can significantly increase when massive number of devices simultaneously access the channel. To address this issue and improve the reliability of the random access, an adaptive packet aggregation method is proposed. With the proposed method, a device does not trigger a random access for every single packet. Instead, it starts a random access when the number of aggregated packets reaches a given threshold. This method reduces the packet collision rate at the expense of an extra latency, which is used to accumulate multiple packets into a single transmission unit. Therefore, the tradeoff between packet loss rate and channel access latency has to be carefully selected. We use semi-Markov model to derive the packet loss rate and channel access latency as functions of packet aggregation number. Hence, the optimal amount of aggregated packets can be found, which keeps the loss rate below the desired value while minimizing the access latency. We also apply for the idea of packet aggregation for power saving, where a device aggregates as many packets as possible until the latency constraint is reached. Simulations are carried out to evaluate our methods. We find that the packet loss rate and/or power consumption are significantly reduced with the proposed method. PMID- 26900390 TI - Gene expression analysis supports tumor threshold over 2.0 cm for T-category breast cancer. AB - Tumor size, as indicated by the T-category, is known as a strong prognostic indicator for breast cancer. It is common practice to distinguish the T1 and T2 groups at a tumor size of 2.0 cm. We investigated the 2.0-cm rule from a new point of view. Here, we try to find the optimal threshold based on the differences between the gene expression profiles of the T1 and T2 groups (as defined by the threshold). We developed a numerical algorithm to measure the overall differential gene expression between patients with smaller tumors and those with larger tumors among multiple expression datasets from different studies. We confirmed the performance of the proposed algorithm by a simulation study and then applied it to three different studies conducted at two Norwegian hospitals. We found that the maximum difference in gene expression is obtained at a threshold of 2.2-2.4 cm, and we confirmed that the optimum threshold was over 2.0 cm, as indicated by a validation study using five publicly available expression datasets. Furthermore, we observed a significant differentiation between the two threshold groups in terms of time to local recurrence for the Norwegian datasets. In addition, we performed an associated network and canonical pathway analyses for the genes differentially expressed between tumors below and above the given thresholds, 2.0 and 2.4 cm, using the Norwegian datasets. The associated network function illustrated a cellular assembly of the genes for the 2.0-cm threshold: an energy production for the 2.4-cm threshold and an enrichment in lipid metabolism based on the genes in the intersection for the 2.0- and 2.4 cm thresholds. PMID- 26900392 TI - Physicians' working conditions in hospitals from the students' perspective (iCEPT Study)-results of a web-based survey. AB - BACKGROUND: Medical students undergo numerous clinical clerkships. On these occasions they are confronted with current working conditions in hospitals. Because of the many implications of the students' perceptions of these working conditions, it is important to assess those. Hereby the focus was put on the students' perception of their supervising physician. METHODS: This study is a part of a prospective anonymized web-based survey (iCEPT-Study). The study was conducted in Germany among medical students after their clinical rotations. 1587 medical students took part in this study (63,0 % female and 37,0 % male). 11259 were invited to take part (response rate of 14,1 %). In this study a questionnaire was used which was based on the Effort-Reward-Imbalance (ERI) model and the Job-Demand-Control (JDC) model. A mathematical calculated ratio (ER- and JDC-Ratio; combined as 'ER/JDC-Ratio') was used to measure the students' perceptions of working conditions, namely distress (primary outcome). As a secondary outcome perceived job satisfaction was measured. RESULTS: Distress was perceived by 67.4 % (95 %-CI: 65.1|69.7) of the students. 54.1 % (95 %-CI: 51.7|56.6) of polled students stated that their supervising physician seemed to be very satisfied with his job. Analysis of age distribution revealed that the proportion of students' who perceived their supervising physician as very satisfied with his job dropped from 72.5 % among under 20-year olds to 63.0 % among 20-24-year olds and was at 44.5 % among the over 30-year olds. Looking at the specialty, the specialty of surgery was rated with the highest distress prevalence (ER/JDC-Ratio > 1): 81.3 % of students stated that their supervising surgeon encountered unfavorable working conditions. CONCLUSION: Two out of three medical students rated the physicians working conditions as stressful. This implicates that already in this early phase of their career the majority of medical students get to know the hospital as an unfavorable workplace concerning working conditions. To facilitate the transition from medical schools to hospitals working conditions of physicians must be improved. PMID- 26900391 TI - Probiotics in prevention and treatment of obesity: a critical view. AB - The worldwide prevalence of obesity more than doubled between 1980 and 2014. The obesity pandemic is tightly linked to an increase in energy availability, sedentariness and greater control of ambient temperature that have paralleled the socioeconomic development of the past decades. The most frequent cause which leads to the obesity development is a dysbalance between energy intake and energy expenditure. The gut microbiota as an environmental factor which influence whole body metabolism by affecting energy balance but also inflammation and gut barrier function, integrate peripheral and central food intake regulatory signals and thereby increase body weight. Probiotics have physiologic functions that contribute to the health of gut microbiota, can affect food intake and appetite, body weight and composition and metabolic functions through gastrointestinal pathways and modulation of the gut bacterial community. PMID- 26900393 TI - Utilization of personal protective equipment and associated factors among textile factory workers at Hawassa Town, Southern Ethiopia. AB - BACKGROUND: Use of personal protective equipment is one of the important measures to safeguard workers from exposure to occupational hazards, especially in developing countries. However, there is a dearth of studies describing personal protective equipment utilization in Ethiopia. The present study has determined the magnitude of personal protective equipment utilization and identified associated factors among textile factory workers at Hawassa Town, southern Ethiopia. METHODS: An institution-based cross-sectional study was conducted among textile factory workers at Hawassa Town, southern Ethiopia from January to March 2014. Stratified sampling followed by simple random sampling techniques was used to select the total of 660 study participants. A pre-tested and structured questionnaire was used to collect data. Multivariate analyses were employed to see the effect of explanatory variables on dependent variable. RESULTS: The magnitude of personal protective equipment utilization was 82.4 %. Service duration of >10 years [AOR: 0.23, 95 % CI: (0.09, 0.58)], availability of personal protective equipments [AOR: 21.73, 95 % CI: (8.62, 54.79)], shift work [AOR: 2.28, 95 % CI: (1.12, 4.66)], alcohol drinking [AOR: 0.26, 95 % CI: (0.10, 0.66)], and cigarette smoking [AOR: 0.20, 95 % CI: (0.05, 0.78)] were factors significantly associated with use of personal protective equipment. CONCLUSION: In this study a relatively higher personal protective equipment utilization rate was reported compared to other studies in developing countries. However, this does not mean that there will be no need for further strengthening the safety programs as there are significant proportion of the workers still does not use all the necessary personal protective equipment during work. Interventions to promote use personal protective equipment should focus on areas, such as service duration, availability of protective equipment, presence of shift work, and control of substance abuse. PMID- 26900394 TI - Health status of male steel workers at an electric arc furnace (EAF) in Trentino, Italy. AB - BACKGROUND: The aim of this retrospective cohort study was to determine if the workers of an Electric Arc Furnace (EAF), which recycles scrap, had higher mortality and morbidity due to possible exposure to pollutants at work. EAFs do not run on coke ovens. In EAFs 40 % of the particulate matter (PM) is made up of PM 2.5. The foundry dust contained iron, aluminum, zinc, manganese, lead, chromium, nickel, cadmium, mercury, arsenic, polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls and dioxins. METHODS: Mortality study: a cohort of 331 exposed workers (6731 person-years) was studied from 19/03/1979 to 31/12/2009 (mean follow up 20.7 years). The group of exposed workers was compared to the general population and to a small control group of 32 workers from the same company. Morbidity study: rates of exemption from health fee for the seven major diseases of 235 exposed workers were compared to the rates of exemption in the Province of Trento. RESULTS: Mortality study: an excess mortality was found in the exposed workers as compared to the general population (SMR 1.13; 95 % CI: 0.76-1.62; 29 deaths) and to the internal group (RR 2.34; 95 % CI: 0.39-95.7). The mortality rate was increased for all tumours (SMR 1.36; 95 % CI: 0.75-2.29; 14 cases), for lung cancer (SMR 3.35; 95 % CI 1.45-6.60; 8 cases), for ischemic heart disease (SMR 1.27; 95 % CI: 0.35-3.26; 4 cases), for chronic liver disease (SMR 1.16; 95 % CI: 0.14-4.20; 2 cases) and for injury and poisoning (SMR 1.32; 95 % CI: 0.48-2.88; 6 cases). Morbidity study: there was a statistically significant increase of diabetes, rheumatoid arthritis, hypertension and cardiovascular diseases in exposed workers. CONCLUSIONS: With the limitations of this relatively small cohort, we found a statistically significant increase of diabetes, cardiovascular diseases and deaths due to lung cancer in exposed workers. These findings cannot be explained by PAH exposure alone; metal particulates are the most important pollutants in the working area of EAFs. A reliable method for measuring metal PM in tissues is urgently needed for exposure assessment. This study underlines the necessity to maximize the standards of security toward foundry dusts/diffuse emission. Further studies on EAF's are needed to confirm our findings and to increase statistical power. PMID- 26900395 TI - The assessment of inflammatory activity and toxicity of treated sewage using RAW264.7 cells. AB - Toxicity and inflammatory activity of wastewater samples were evaluated using RAW264.7 cells as a bioassay model. The RAW264.7 cell cultures were exposed to sterile filtered wastewater samples collected from a sewage treatment plant. Cell viability was evaluated using WST-1 and XTT assays. Inflammatory effects of samples were assessed by determination of nitric oxide (NO) and interleukin 6 (IL 6). The NO was estimated using the Griess reaction and IL-6 was measured by enzyme-linked immunoassay. All samples had no toxicity effects to RAW264.7 cells, however they significantly (P < 0.001) induced NO and IL-6 production. The highest NO (12.5 +/- 0.38 MUM) and IL-6 (25383.84 +/- 2327 pg/mL) production was induced by postbiofiltration sample. Final effluent induced the lowest inflammatory response, which indicates effective sewage treatment. In conclusion, wastewater samples can induce inflammatory activities in RAW264.7 cells. The RAW264.7 cells, therefore, can be used as a model for monitoring the quality of treated sewage. PMID- 26900397 TI - Determination of heavy metals in the soils of tea plantations and in fresh and processed tea leaves: an evaluation of six digestion methods. AB - BACKGROUND: The aim of this study was to determine the levels of cadmium (Cd), chromium (Cr), lead (Pb), arsenic (As) and selenium (Se) in (1) fresh tea leaves, (2) processed (black) tea leaves and (3) soils from tea plantations originating from Bangladesh. METHODS: Graphite furnace atomic absorption spectrometry (GF AAS) was used to evaluate six digestion methods, (1) nitric acid, (2) nitric acid overnight, (3) nitric acid-hydrogen peroxide, (4) nitric-perchloric acid, (5) sulfuric acid, and (6) dry ashing, to determine the most suitable digestion method for the determination of heavy metals in the samples. RESULTS: The concentration ranges of Cd, Pb, As and Se in fresh tea leaves were from 0.03 0.13, 0.19-2.06 and 0.47-1.31 ug/g, respectively while processed tea contained heavy metals at different concentrations: Cd (0.04-0.16 ug/g), Cr (0.45-10.73 ug/g), Pb (0.07-1.03 ug/g), As (0.89-1.90 ug/g) and Se (0.21-10.79 ug/g). Moreover, the soil samples of tea plantations also showed a wide range of concentrations: Cd (0.11-0.45 ug/g), Pb (2.80-66.54 ug/g), As (0.78-4.49 ug/g), and Se content (0.03-0.99 ug/g). Method no. 2 provided sufficient time to digest the tea matrix and was the most efficient method for recovering Cd, Cr, Pb, As and Se. Methods 1 and 3 were also acceptable and can be relatively inexpensive, easy and fast. The heavy metal transfer factors in the investigated soil/tea samples decreased as follows: Cd > As > Se > Pb. CONCLUSION: Overall, the present study gives current insights into the heavy metal levels both in soils and teas commonly consumed in Bangladesh. PMID- 26900396 TI - Nanoscale Assemblies of Small Molecules Control the Fate of Cells. AB - Being driven by non-covalent interactions, the formation of functional assemblies (or aggregates) of small molecules at nanoscale is a more common process in water than one would think. While most efforts on self-assembly in cellular environment concentrate on the assemblies of proteins (e.g., microtubules or amyloid fibers), nanoscale assemblies of small molecules are emerging functional entities that exhibit important biological function in cellular environments. This review describes the increasing efforts on the exploration of nanoscale assemblies of small molecules that largely originate from the serendipitous observations in research fields other than nanoscience and technology. Specifically, we describe that nanoscale assemblies of small molecules exhibit unique biological functions in extracellular and intracellular environment, thus inducing various cellular responses, like causing cell death or promoting cell proliferation. We first survey certain common feature of nanoscale molecular assemblies, then discuss several specific examples, such as, nanoscale assemblies of small peptides accumulated in the cells for selectively inhibiting cancer cells via promiscuous interactions with proteins, and nanoscale assemblies of a glycoconjugate for promoting the proliferation of stem cells or for suppressing immune responses. Subsequently, we emphasize the spatiotemporal control of nanoscale assemblies for controlling the cell fate, particularly illustrate a paradigm-shifting approach enzyme-instructed self-assembly (EISA), that is, the integration of enzymatic reaction and self-assembly-for generating nanoscale assemblies from innocuous monomers for selectively inhibiting cancer cells. Moreover, we introduce a convenient assay for proteomic study of the proteins that interact with nanoscale assemblies of small molecules in cellular environment. Furthermore, we introduce the use of ligand-receptor interaction to catalyze the formation of nanoscale assemblies. By illustrating these experimental strategies for controlling the formation of nanoscale assemblies of small molecules and for identifying their corresponding protein targets, we aim to highlight that, though not being defined at the genetic level, nanoscale assemblies of small molecules are able to perform many critical biological functions. We envision that nanoscale assemblies of small molecules are a new frontier at the intersection of nanoscience and cell biology and biomedicine. In addition, we discuss the challenges and perspectives of relevant potential biomedical applications of nanoscale assemblies of small molecules. PMID- 26900399 TI - Erratum to: Indirect land use changes of biofuel production - a review of modelling efforts and policy developments in the European Union. AB - [This corrects the article DOI: 10.1186/1754-6834-7-35.]. PMID- 26900398 TI - Service user and family member perspectives on services for mental health, substance use/addiction, and violence: a qualitative study of their goals, experiences and recommendations. AB - BACKGROUND: Mental health and substance use disorders (MSD) are significant public health concerns that often co-occur with violence. To improve services that address MSD and violence [MSD(V)], it is critical to understand the perspectives of those most affected, people who have sought help for MSD(V) (i.e., "service users"), especially those with co-occurring issues, as well as their family members. METHODS: We conducted structured interviews with 73 service users and 41 family members of service users in two Ontario communities (one urban, one rural) regarding their goals related to help-seeking, positive and negative experiences, and recommendations for improving systems of care. RESULTS: Overall, participants expressed a need for services that: (1) are respectful, nonjudgmental, and supportive, help service users to feel more 'normal' and include education to reduce stigma; (2) are accessible, varied and publicly funded, thereby meeting individual needs and addressing equity concerns at a systems level; and (3) are coordinated, holistic and inclusive of family members who often support service users. CONCLUSIONS: The findings provide a rich understanding of how service users and their families perceive services for MSD(V) issues and identify key ways to better meet their needs. PMID- 26900400 TI - Sexual crossing of thermophilic fungus Myceliophthora heterothallica improved enzymatic degradation of sugar beet pulp. AB - BACKGROUND: Enzymatic degradation of plant biomass requires a complex mixture of many different enzymes. Like most fungi, thermophilic Myceliophthora species therefore have a large set of enzymes targeting different linkages in plant polysaccharides. The majority of these enzymes have not been functionally characterized, and their role in plant biomass degradation is unknown. The biotechnological challenge is to select the right set of enzymes to efficiently degrade a particular biomass. This study describes a strategy using sexual crossing and screening with the thermophilic fungus Myceliophthora heterothallica to identify specific enzymes associated with improved sugar beet pulp saccharification. RESULTS: Two genetically diverse M. heterothallica strains CBS 203.75 and CBS 663.74 were used to generate progenies with improved growth on sugar beet pulp. One progeny, named SBP.F1.2.11, had a different genetic pattern from the parental strains and had improved saccharification activity after the growth on 3 % sugar beet pulp. The improved SBP saccharification was not explained by altered activities of the major (hemi-)cellulases. Exo-proteome analysis of progeny and parental strains after 7-day growth on sugar beet pulp showed that only 17 of the 133 secreted CAZy enzymes were more abundant in progeny SBP.F1.2.11. Particularly one enzyme belonging to the carbohydrate esterase family 5 (CE5) was more abundant in SBP.F1.2.11. This CE5-CBM1 enzyme, named as Axe1, was phylogenetically related to acetyl xylan esterases. Biochemical characterization of Axe1 confirmed de-acetylation activity with optimal activities at 75-85 degrees C and pH 5.5-6.0. Supplementing Axe1 to CBS 203.75 enzyme set improved release of xylose and glucose from sugar beet pulp. CONCLUSIONS: This study identified beneficial enzymes for sugar beet pulp saccharification by selecting progeny with improved growth on this particular substrate. Saccharification of sugar beet pulp was improved by supplementing enzyme mixtures with a previously uncharacterized CE5-CBM1 acetyl xylan esterase. This shows that sexual crossing and selection of M. heterothallica are the successful strategy to improve the composition of enzyme mixtures for efficient plant biomass degradation. PMID- 26900401 TI - Comparative analysis of the secretomes of Schizophyllum commune and other wood decay basidiomycetes during solid-state fermentation reveals its unique lignocellulose-degrading enzyme system. AB - BACKGROUND: The genome of Schizophyllum commune encodes a diverse repertoire of degradative enzymes for plant cell wall breakdown. Recent comparative genomics study suggests that this wood decayer likely has a mode of biodegradation distinct from the well-established white-rot/brown-rot models. However, much about the extracellular enzyme system secreted by S. commune during lignocellulose deconstruction remains unknown and the underlying mechanism is poorly understood. In this study, extracellular proteins of S. commune colonizing Jerusalem artichoke stalk were analyzed and compared with those of two white-rot fungi Phanerochaete chrysosporium and Ceriporiopsis subvermispora and a brown-rot fungus Gloeophyllum trabeum. RESULTS: Under solid-state fermentation (SSF) conditions, S. commune displayed considerably higher levels of hydrolytic enzyme activities in comparison with those of P. chrysosporium, C. subvermispora and G. trabeum. During biodegradation process, this fungus modified the lignin polymer in a way which was consistent with a hydroxyl radical attack, similar to that of G. trabeum. The crude enzyme cocktail derived from S. commune demonstrated superior performance over a commercial enzyme preparation from Trichoderma longibrachiatum in the hydrolysis of pretreated lignocellulosic biomass at low enzyme loadings. Secretomic analysis revealed that compared with three other fungi, this species produced a higher diversity of carbohydrate-degrading enzymes, especially hemicellulases and pectinases acting on polysaccharide backbones and side chains, and a larger set of enzymes potentially supporting the generation of hydroxyl radicals. In addition, multiple non-hydrolytic proteins implicated in enhancing polysaccharide accessibility were identified in the S. commune secretome, including lytic polysaccharide monooxygenases (LPMOs) and expansin-like proteins. CONCLUSIONS: Plant lignocellulose degradation by S. commune involves a hydroxyl radical-mediated mechanism for lignocellulose modification in parallel with the synergistic system of various polysaccharide degrading enzymes. Furthermore, the complex enzyme system of S. commune holds significant potential for application in biomass saccharification. These discoveries will help unveil the diversity of natural lignocellulose-degrading mechanisms, and advance the design of more efficient enzyme mixtures for the deconstruction of lignocellulosic feedstocks. PMID- 26900402 TI - Transcriptomic analysis of the effects of Toll-like receptor 4 and its ligands on the gene expression network of hepatic stellate cells. AB - BACKGROUND: Intact Toll-like receptor 4 (TLR4) has been identified in hepatic stellate cells (HSCs), the primary fibrogenic cell type in liver. Here, we investigated the impact of TLR4 signaling on the gene expression network of HSCs by comparing the transcriptomic changes between wild-type (JS1) and TLR4 knockout (JS2) murine HSCs in response to two TLR4 ligands, lipopolysacchride (LPS), or high-mobility group box 1 (HMGB1). RESULTS: Whole mouse genome microarray was performed for gene expression analysis. Gene interaction and co-expression networks were built on the basis of ontology and pathway analysis by Kyoto Encyclopedia of Genes and Genomes (KEGG). Gene expression profiles are markedly different between Wild type (JS1) and TLR4 knockout (JS2) HSCs under basal conditions or following stimulation with LPS or HMGB1. The differentially expressed genes between TLR4 intact and null HSCs were enriched in signaling pathways including p53, mTOR, NOD-like receptor, Jak-STAT, chemokine, focal adhesion with some shared downstream kinases, and transcriptional factors. Venn analysis revealed that TLR4-dependent, LPS-responsive genes were clustered into pathways including Toll-like receptor and PI3K-Akt, whereas TLR4-dependent, HMGB1 responsive genes were clustered into pathways including metabolism and phagosome signaling. Genes differentially expressed that were categorized to be TLR4 dependent and both LPS- and HMGB1-responsive were enriched in cell cycle, ubiquitin mediated proteolysis, and mitogen-activated protein kinase (MAPK) signaling pathways. CONCLUSIONS: TLR4 mediates complex gene expression alterations in HSCs. The affected pathways regulate a wide spectrum of HSC functions, including inflammation, fibrogenesis, and chemotaxis, as well as cell growth and metabolism. There are common and divergent regulatory signaling downstream of LPS and HMGB1 stimulation via TLR4 on HSCs. These findings emphasize the complex cascades downstream of TLR4 in HSCs that could influence their cellular biology and function. PMID- 26900404 TI - What is healthcare for? PMID- 26900403 TI - Complex intrachromosomal rearrangement in 1q leading to 1q32.2 microdeletion: a potential role of SRGAP2 in the gyrification of cerebral cortex. AB - BACKGROUND: Van der Woude syndrome (MIM: 119300, VWS) is a dominantly inherited and the most common orofacial clefting syndrome; it accounts for ~2 % of all cleft lip and palate cases. Intellectual disability (ID) is characterized by significant limitations, both in intellectual functioning (cognitive deficit) and in adaptive behavior as expressed in conceptual, social and practical adaptive skills. Karyotyping has been the first standard test for the detection of genetic imbalance in patients with ID for more than 35 years. Advances in genetic diagnosis have laid chromosomal microarrays (CMA) as a new standard and first first-line test for diagnosis of patients with ID, as well as other conditions, such as autism spectrum disorders or multiple congenital anomalies. CASE PRESENTATION: The present case was initially studied due to unexplained cognitive deficit. Physical examination at the age of 18 years revealed cleft palate, lower lip pits and hypodontia, accompanied with other dysmorphic features and absence of speech. Brain MRI uncovered significantly reduced overall volume of gray matter and cortical gyrification. Banding cytogenetics revealed an indistinct intrachromosomal rearrangement in the long arm of one chromosome 1, and subsequent microarray analyses identified a 5.56 Mb deletion in 1q32.1-1q32.3, encompassing 52 genes; included were the entire IRF6 gene (whose mutations/deletions underlay VWS) and SRGAP2, a gene with an important role in neuronal migration during development of cerebral cortex. Besides, a duplication in 3q26.32 (1.9 Mb in size) comprising TBL1XR1 gene was identified. Multicolor banding for chromosome 1 and molecular cytogenetics applying a battery of locus specific probes covering 1q32.1 to 1q44 characterized a four breakpoint insertional-rearrangement-event, resulting in 1q32.1-1q32.3 deletion. CONCLUSIONS: Considering that the human-specific three-fold segmental duplication of SRGAP2 gene evolutionary corresponds to the beginning of neocortical expansion, we hypothesize that aberrations in SRGAP2 are strong candidates underlying specific brain abnormalities, namely reduced volume of grey matter and reduced gyrification. PMID- 26900405 TI - Genomic characterization and assessment of the virulence and antibiotic resistance of the novel species Paenibacillus sp. strain VT-400, a potentially pathogenic bacterium in the oral cavity of patients with hematological malignancies. AB - BACKGROUND: Paenibacillus sp. strain VT-400, a novel spore-forming bacterium, was isolated from patients with hematological malignancies. METHODS: Paenibacillus sp. strain VT-400 was isolated from the saliva of four children with acute lymphoblastic leukemia. The genome was annotated using RAST and the NCBI Prokaryotic Genome Annotation Pipeline to characterize features of antibiotic resistance and virulence factors. Susceptibility to antibiotics was determined by the Kirby-Bauer disc diffusion method. We used a mouse model of pneumonia to study virulence in vivo. Mice were challenged with 7.5 log10-9.5 log10 CFU, and survival was monitored over 7 days. Bacterial load was measured in the lungs and spleen of surviving mice 48 h post-infection to reveal bacterial invasion and dissemination. RESULTS: Whole-genome sequencing revealed a large number of virulence factors such as hemolysin D and CD4+ T cell-stimulating antigen. Furthermore, the strain harbors numerous antibiotic resistance genes, including small multidrug resistance proteins, which have never been previously found in the Paenibacillus genus. We then compared the presence of antibiotic resistance genes against results from antibiotic susceptibility testing. Paenibacillus sp. strain VT-400 was found to be resistant to macrolides such as erythromycin and azithromycin, as well as to chloramphenicol and trimethoprim-sulphamethoxazole. Finally, the isolate caused mortality in mice infected with >=8.5 log10 CFU. CONCLUSIONS: Based on our results and on the available literature, there is yet no strong evidence that shows Paenibacillus species as an opportunistic pathogen in immunocompromised patients. However, the presence of spore-forming bacteria with virulence and antibiotic resistance genes in such patients warrants special attention because infections caused by spore-forming bacteria are poorly treatable. PMID- 26900406 TI - Effects of using structured templates for recalling chemistry experiments. AB - BACKGROUND: The way that we recall information is dependent upon both the knowledge in our memories and the conditions under which we recall the information. Electronic Laboratory Notebooks can provide a structured interface for the capture of experiment records through the use of forms and templates. These templates can be useful by providing cues to help researchers to remember to record particular aspects of their experiment, but they may also constrain the information that is recorded by encouraging them to record only what is asked for. It is therefore unknown whether using structured templates for capturing experiment records will have positive or negative effects on the quality and usefulness of the records for assessment and future use. In this paper we report on the results of a set of studies investigating the effects of different template designs on the recording of experiments by undergraduate students and academic researchers. RESULTS: The results indicate that using structured templates to write up experiments does make a significant difference to the information that is recalled and recorded. These differences have both positive and negative effects, with templates prompting the capture of specific information that is otherwise forgotten, but also apparently losing some of the personal elements of the experiment experience such as observations and explanations. Other unexpected effects were seen with templates that can change the information that is captured, but also interfere with the way an experiment is conducted. CONCLUSIONS: Our results showed that using structured templates can improve the completeness of the experiment context information captured but can also cause a loss of personal elements of the experiment experience when compared with allowing the researcher to structure their own record. The results suggest that interfaces for recording information about chemistry experiments, whether paper-based questionnaires or templates in Electronic Laboratory Notebooks, can be an effective way to improve the quality of experiment write-ups, but that care needs to be taken to ensure that the correct cues are provided.Graphical abstractScientists have traditionally recorded their research in paper notebooks, a format that provides great flexibility for capturing information. In contrast, Electronic Laboratory Notebooks frequently make use of forms or structured templates for capturing experiment records. Structured templates can provide cues that can improve record quality by increasing the amount of information captured and encouraging consistency. However, using the wrong cues can lead to a loss of personal elements of the experiment experience and frustrate users. This image shows two participants from one of our studies recording their experiment using a computer-based template. PMID- 26900409 TI - Bio-conjugation of antioxidant peptide on surface-modified gold nanoparticles: a novel approach to enhance the radical scavenging property in cancer cell. AB - BACKGROUND: Functionalized gold nanoparticles are emerging as a promising nanocarrier for target specific delivery of the therapeutic molecules in a cancer cell, as a result it targeted selectively to the cancer cell and minimized the off-target effect. The functionalized nanomaterial (bio conjugate) brings novel functional properties, for example, the high payload of anticancer, antioxidant molecules and selective targeting of the cancer molecular markers. The current study reported the synthesis of multifunctional bioconjugate (GNPs-Pep-A) to target the cancer cell. METHODS: The GNPs-Pep-A conjugate was prepared by functionalization of GNPs with peptide-A (Pro-His-Cys-Lys-Arg-Met; Pep-A) using thioctic acid as a linker molecule. The GNPs-Pep-A was characterized and functional efficacy was tested using Retinoblastoma (RB) cancer model in vitro. RESULTS: The GNPs-Pep-A target the reactive oxygen species (ROS) in RB, Y79, cancer cell more effectively, and bring down the ROS up to 70 % relative to control (untreated cells) in vitro. On the other hand, Pep-A and GNPs showed 40 and 9 % reductions in ROS, respectively, compared to control. The effectiveness of bioconjugate indicates the synergistic effect, due to the coexistence of both organic (Pep-A) and inorganic phase (GNPs) in novel GNPs-Pep-A functional material. In addition to this, it modulates the mRNA expression of antioxidant genes glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase (CAT) by two-threefolds as observed. CONCLUSIONS: The effects of GNPs-Pep-A on ROS reduction and regulation of antioxidant genes confirmed that Vitis vinifera L. polyphenol-coated GNPs synergistically improve the radical scavenging properties and enhanced the apoptosis of cancer cell. PMID- 26900407 TI - Fibronectin Mechanobiology Regulates Tumorigenesis. AB - Fibronectin (Fn) is an essential extracellular matrix (ECM) glycoprotein involved in both physiological and pathological processes. The structure-function relationship of Fn has been and is still being studied, as changes in its molecular structure are integral in regulating (or dysregulating) its biological activities via its cell, matrix component, and growth factor binding sites. Fn comprises three types of repeating modules; among them, FnIII modules are mechanically unstable domains that may be extended/unfolded upon cell traction and either uncover cryptic binding sites or disrupt otherwise exposed binding sites. Cells assemble Fn into a fibrillar network; its conformational flexibility implicates Fn as a critical mechanoregulator of the ECM. Fn has been shown to contribute to altered stroma remodeling during tumorigenesis. This review will discuss (i) the significance of the structure-function relationship of Fn at both the molecular and the matrix scales, (ii) the role of Fn mechanobiology in the regulation of tumorigenesis, and (iii) Fn-related advances in cancer therapy development. PMID- 26900408 TI - Heading in the Right Direction: Understanding Cellular Orientation Responses to Complex Biophysical Environments. AB - The aim of cardiovascular regeneration is to mimic the biological and mechanical functioning of tissues. For this it is crucial to recapitulate the in vivo cellular organization, which is the result of controlled cellular orientation. Cellular orientation response stems from the interaction between the cell and its complex biophysical environment. Environmental biophysical cues are continuously detected and transduced to the nucleus through entwined mechanotransduction pathways. Next to the biochemical cascades invoked by the mechanical stimuli, the structural mechanotransduction pathway made of focal adhesions and the actin cytoskeleton can quickly transduce the biophysical signals directly to the nucleus. Observations linking cellular orientation response to biophysical cues have pointed out that the anisotropy and cyclic straining of the substrate influence cellular orientation. Yet, little is known about the mechanisms governing cellular orientation responses in case of cues applied separately and in combination. This review provides the state-of-the-art knowledge on the structural mechanotransduction pathway of adhesive cells, followed by an overview of the current understanding of cellular orientation responses to substrate anisotropy and uniaxial cyclic strain. Finally, we argue that comprehensive understanding of cellular orientation in complex biophysical environments requires systematic approaches based on the dissection of (sub)cellular responses to the individual cues composing the biophysical niche. PMID- 26900411 TI - Haloarchaeal gas vesicle nanoparticles displaying Salmonella antigens as a novel approach to vaccine development. AB - A safe, effective, and inexpensive vaccine against typhoid and other Salmonella diseases is urgently needed. In order to address this need, we are developing a novel vaccine platform employing buoyant, self-adjuvanting gas vesicle nanoparticles (GVNPs) from the halophilic archaeon Halobacterium sp. NRC-1, bioengineered to display highly conserved Salmonella enterica antigens. As the initial antigen for testing, we selected SopB, a secreted inosine phosphate effector protein injected by pathogenic S. enterica bacteria during infection into the host cells. Two highly conserved sopB gene segments near the 3'-region, named sopB4 and sopB5, were each fused to the gvpC gene, and resulting SopB-GVNPs were purified by centrifugally accelerated flotation. Display of SopB4 and SopB5 antigenic epitopes on GVNPs was established by Western blotting analysis using antisera raised against short synthetic peptides of SopB. Immunostimulatory activities of the SopB4 and B5 nanoparticles were tested by intraperitoneal administration of SopB-GVNPs to BALB/c mice which had been immunized with S. enterica serovar Typhimurium 14028 DeltapmrG-HM-D (DV-STM-07), a live attenuated vaccine strain. Proinflammatory cytokines IFN-gamma, IL-2, and IL-9 were significantly induced in mice boosted with SopB5-GVNPs, consistent with a robust Th1 response. After challenge with virulent S. enterica serovar Typhimurium 14028, bacterial burden was found to be diminished in spleen of mice boosted with SopB4-GVNPs and absent or significantly diminished in liver, mesenteric lymph node, and spleen of mice boosted with SopB5-GVNPs, indicating that the C-terminal portions of SopB displayed on GVNPs elicit a protective response to Salmonella infection in mice. SopB antigen-GVNPs were also found to be stable at elevated temperatures for extended periods without refrigeration. The results show that bioengineered GVNPs are likely to represent a valuable platform for antigen delivery and development of improved vaccines against Salmonella and other diseases. PMID- 26900410 TI - Development of 5' LTR DNA methylation of latent HIV-1 provirus in cell line models and in long-term-infected individuals. AB - BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) latency represents the major barrier to virus eradication in infected individuals because cells harboring latent HIV-1 provirus are not affected by current antiretroviral therapy (ART). We previously demonstrated that DNA methylation of HIV-1 long terminal repeat (5' LTR) restricts HIV-1 reactivation and, together with chromatin conformation, represents an important mechanism of HIV-1 latency maintenance. Here, we explored the new issue of temporal development of DNA methylation in latent HIV-1 5' LTR. RESULTS: In the Jurkat CD4(+) T cell model of latency, we showed that the stimulation of host cells contributed to de novo DNA methylation of the latent HIV-1 5' LTR sequences. Consecutive stimulations of model CD4(+) T cell line with TNF-alpha and PMA or with SAHA contributed to the progressive accumulation of 5' LTR DNA methylation. Further, we showed that once established, the high DNA methylation level of the latent 5' LTR in the cell line model was a stable epigenetic mark. Finally, we explored the development of 5' LTR DNA methylation in the latent reservoir of HIV-1-infected individuals who were treated with ART. We detected low levels of 5' LTR DNA methylation in the resting CD4(+) T cells of the group of patients who were treated for up to 3 years. However, after long-term ART, we observed an accumulation of 5' LTR DNA methylation in the latent reservoir. Importantly, within the latent reservoir of some long-term-treated individuals, we uncovered populations of proviral molecules with a high density of 5' LTR CpG methylation. CONCLUSIONS: Our data showed the presence of 5' LTR DNA methylation in the long-term reservoir of HIV-1 infected individuals and implied that the transient stimulation of cells harboring latent proviruses may contribute, at least in part, to the methylation of the HIV-1 promoter. PMID- 26900413 TI - Time Evolution of the Wettability of Supported Graphene under Ambient Air Exposure. AB - The wettability of graphene is both fundamental and crucial for interfacing in most applications, but a detailed understanding of its time evolution remains elusive. Here we systematically investigate the wettability of metal-supported, chemical vapor deposited graphene films as a function of ambient air exposure time using water and various other test liquids with widely different surface tensions. The wettability of graphene is not constant, but varies with substrate interactions and air exposure time. The substrate interactions affect the initial graphene wettability, where, for instance, water contact angles of ~85 and ~61 degrees were measured for Ni and Cu supported graphene, respectively, after just minutes of air exposure. Analysis of the surface free energy components indicates that the substrate interactions strongly influence the Lewis acid-base component of supported graphene, which is considerably weaker for Ni supported graphene than for Cu supported graphene, suggesting that the classical van der Waals interaction theory alone is insufficient to describe the wettability of graphene. For prolonged air exposure, the effect of physisorption of airborne contaminants becomes increasingly dominant, resulting in an increase of water contact angle that follows a universal linear-logarithmic relationship with exposure time, until saturating at a maximum value of 92-98 degrees . The adsorbed contaminants render all supported graphene samples increasingly nonpolar, although their total surface free energy decreases only by 10-16% to about 37-41 mJ/m2. Our finding shows that failure to account for the air exposure time may lead to widely different wettability values and contradicting arguments about the wetting transparency of graphene. PMID- 26900414 TI - Paying on the margin for medical care: Evidence from breast cancer treatments. AB - We present a simple graphical framework to illustrate the potential welfare gains from a "top-up" health insurance policy requiring patients to pay the incremental price for more expensive treatment options. We apply this framework to breast cancer treatments, where lumpectomy with radiation therapy is more expensive than mastectomy but generates similar average health benefits. We estimate the relative demand for lumpectomy using variation in distance to the nearest radiation facility, and estimate that the "top-up" policy increases social welfare by $700-2,500 per patient relative to two common alternatives. We briefly discuss additional tradeoffs that arise from an ex-ante perspective. PMID- 26900412 TI - BFLCRM: A BAYESIAN FUNCTIONAL LINEAR COX REGRESSION MODEL FOR PREDICTING TIME TO CONVERSION TO ALZHEIMER'S DISEASE. AB - The aim of this paper is to develop a Bayesian functional linear Cox regression model (BFLCRM) with both functional and scalar covariates. This new development is motivated by establishing the likelihood of conversion to Alzheimer's disease (AD) in 346 patients with mild cognitive impairment (MCI) enrolled in the Alzheimer's Disease Neuroimaging Initiative 1 (ADNI-1) and the early markers of conversion. These 346 MCI patients were followed over 48 months, with 161 MCI participants progressing to AD at 48 months. The functional linear Cox regression model was used to establish that functional covariates including hippocampus surface morphology and scalar covariates including brain MRI volumes, cognitive performance (ADAS-Cog), and APOE status can accurately predict time to onset of AD. Posterior computation proceeds via an efficient Markov chain Monte Carlo algorithm. A simulation study is performed to evaluate the finite sample performance of BFLCRM. PMID- 26900415 TI - Gulf Implantable Cardioverter-defibrillator Registry Reflects Advanced Cardiac Care in the Arab Gulf. PMID- 26900416 TI - The Gulf Implantable Cardioverter-defibrillator Registry: Rationale, Methodology, and Implementation. AB - BACKGROUND: The implantable cardioverter-defibrillator (ICD) is effective in the prevention of sudden cardiac death in high-risk patients. Little is known about ICD use in the Arabian Gulf. We designed a study to describe the characteristics and outcomes of patients receiving ICDs in the Arab Gulf region. METHODS: Gulf ICD is a prospective, multi-center, multinational, and observational study. All adult patients 18 years or older, receiving a de novo ICD implant and willing to sign a consent form will be eligible. Data on baseline characteristics, ICD indication, procedure and programing, in-hospital, and 1-year outcomes will be collected. Target enrollment is 1500 patients, which will provide adequate precision across a wide range of expected event rates. RESULTS: Fifteen centers in six countries are enrolling patients (Saudi Arabia, United Arab Emirates, Kuwait, Oman, Bahrain, and Qatar). Two-thirds of the centers have dedicated electrophysiology laboratories, and in almost all centers ICDs are implanted exclusively by electrophysiologists. Nearly three-quarters of the centers reported annual ICD implant volumes of <=150 devices, and pulse generator replacements constitute <30% of implants in the majority of centers. Enrollment started in December 2013, and accrual rate increased as more centers entered the study reaching an average of 98 patients per month. CONCLUSIONS: Gulf ICD is the first prospective, observational, multi-center, and multinational study of the characteristics and, the outcomes of patients receiving ICDs in the Arab Gulf region. The study will provide valuable insights into the utilization of and outcomes related to ICD therapy in the Gulf region. PMID- 26900417 TI - A Community-based Cross-sectional Study of Cardiovascular Risk in a Rural Community of Puducherry. AB - BACKGROUND: The World Health Organization (WHO) / International Society of Hypertension (ISH) risk prediction chart can predict the risk of cardiovascular events in any population. AIM: To assess the prevalence of cardiovascular risk factors and to estimate the cardiovascular risk using the WHO/ISH risk charts. MATERIALS AND METHODS: A cross-sectional study was done from November 2011 to January 2012 in a rural area of Puducherry. Method of sampling was a single stage cluster random sampling, and subjects were enrolled depending on their suitability with the inclusion and exclusion criteria. The data collection tool was a piloted and semi-structured questionnaire, while WHO/ISH cardiovascular risk prediction charts for the South-East Asian region was used to predict the cardiovascular risk. Institutional Ethics committee permission was obtained before the start of the study. Statistical analysis was done using SPSS version 16 and appropriate statistical tests were applied. RESULTS: The mean age in years was 54.2 (+/-11.1) years with 46.7% of the participants being male. On application of the WHO/ISH risk prediction charts, almost 17% of the study subjects had moderate or high risk for a cardiovascular event. Additionally, high salt diet, alcohol use and low HDL levels, were identified as the major CVD risk factors. CONCLUSION: To conclude, stratification of people on the basis of risk prediction chart is a major step to have a clear idea about the magnitude of the problem. The findings of the current study revealed that there is a high burden of CVD risk in the rural Puducherry. PMID- 26900418 TI - Right Bundle Branch Block and Electromechanical Coupling of the Right Ventricle: An Echocardiographic Study. AB - BACKGROUND: A growing body of evidence suggests that the presence of a right bundle branch block (RBBB) is a negative prognostic indicator in patients with and without preexisting heart disease. Even though electromechanical activation of the right ventricle (RV) in patients with RBBB and pulmonary hypertension (PH) has been investigated; a direct comparison of the presence of RBBB, on the duration of RV mechanical systole using echocardiography has not been studied. MATERIALS AND METHODS: In this retrospective study, we analyzed the echocardiograms of 40 patients by measuring the magnitude and timing of tricuspid annulus plane systolic excursion (TAPSE) and tricuspid annulus systolic velocity (TA S'). Patients were selected to form four groups of ten patients based on the presence or absence of RBBB and PH to determine if RBBB has any effect on the time-to-peak of TAPSE or TA S', which for our purposes serves as a measure of duration of RV mechanical systole. RESULTS: Our results demonstrate that RBBB leads to a measurable prolongation of TAPSE and TA S' in patients without PH. Time-to-peak of TAPSE or TA S' was not significantly prolonged in patients with PH. CONCLUSIONS: The results of this pilot study show that RV mechanical systole is prolonged in patients with RBBB, and the addition of PH attenuates this change. Additional prospective studies are now required to elucidate further the electrical and mechanical dyssynchrony that occurs as a result of RBBB, and how these new echocardiographic measurements can be applied clinically to risk stratify patients with RBBB and PH. PMID- 26900419 TI - Schwarz Type C Myocardial Bridge Unraveled Post-Thrombus Aspiration in a Patient with Hypertrophic Cardiomyopathy. AB - Hypertrophic cardiomyopathy (HCM), a heterogenous disease with diverse pathology and variable clinical course has a high prevalence of myocardial bridging. Despite the high prevalence of myocardial bridging in HCM patients, acute ST elevation myocardial infarction (STEMI) due to concomitant atherothrombosis proximal to Schwarz type C myocardial bridge unraveled during trans-radial primary percutaneous intervention has rarely been reported in medical literature. Herein, we report a case of Schwarz type C myocardial bridge unmasked postthrombosuction in a patient with HCM presenting with acute STEMI. He had atherothrombosis proximal to the tunneled left anterior descending artery which was successfully stented with drug-eluting stent without the aid of intravascular ultrasound. PMID- 26900420 TI - Cleft Anterior Mitral Leaflet with Supravalvular Aortic Stenosis a Rare Association. AB - A 20 year old female was referred to us for evaluation of effort dyspnoea of NYHA class II with feeble left common carotid, left brachial and left radial artery as compared to other sides. Detail evaluation with two dimensional (2D) transthoracic echocardiographic, 2D transesophageal echocardiography and multidetector computed tomography (MDCT) delineated Cleft AML and diffuse type of supravalvular aortic stenosis. To the best of our knowledge, no such case have been described in the literature where these anomalies co-existed in the same patient. PMID- 26900421 TI - Retrieval of Embolized Intracardiac Peripherally Inserted Central Catheter Line: Novel Percutaneous Technique by Utilizing a Flexible Biopsy Forceps. AB - Peripheral catheter embolization to the heart is common but infrequently reported. In view of the hazardous complications of thrombosis, embolism, infection, arrhythmia and even death, percutaneous retrieval of such foreign bodies is usually attempted. Previously reported percutaneous technique of retrieval mainly involved the snaring technique. Herein, we report a novel nonsurgical retrieval technique for successful removal of a 46 cm long embolized intracardiac peripherally inserted central catheter by utilizing a flexible biopsy forceps. To the best of our knowledge, the use of flexible biopsy forceps for retrieval has hitherto been unreported and this case report therefore adds to the repertoire of percutaneous retrieval techniques for safe and easy removal of embolized catheters to the heart. PMID- 26900422 TI - Incidental Spontaneous Coronary Dissection: An Interventionist's Dilemma. AB - Spontaneous coronary artery dissection (SCAD) is an uncommon entity, frequently presenting as ST-elevation myocardial infarction (MI) or sudden cardiac death. It is usually reported in association with pregnancy and has a high mortality. We present here a case of asymptomatic dissection of the right coronary artery, incidentally detected, in a young normotensive male when coronary angiography was done following acute anterior wall MI. This patient had none of the risk factors to which SCAD is generally ascribed. While management of the infarct-related artery was clear-cut, whether or not to intervene for this nonocclusive dissection was a difficult decision. A conservative approach was finally adopted for the spontaneous dissection and the patient is faring well till date. PMID- 26900423 TI - Left Ventricular Outflow Tract Pseudoaneurysm Formation Following Three Aortic Valve Replacement Surgeries. AB - We present a case of a pseudoaneurysm arising from the left ventricular outflow tract/aortic root as a complication of aortic valve surgery. A 45-year-old Nigerian female presented to our institution's emergency department with chest discomfort. She had three bioprosthetic aortic valve replacements in the preceding year at an outside institution for aortic regurgitation and wanted a second opinion on remaining surgical options. The learning points relevant to this case are as follows: (1) Recognizing potential complications postmultiple valve surgeries, (2) screening patients for chronic infections and rheumatologic conditions that can contribute to failed valve surgeries. PMID- 26900424 TI - Noncompaction Cardiomyopathy: Case Presentation with Cardiac Magnetic Resonance Imaging Findings and Literature Review. AB - Left ventricular noncompaction cardiomyopathy is a very rare condition, yet believed to be often overlooked. It is thought to be caused by the developmental arrest in embryogenesis and characterized by an increase in the noncompacted, trabeculated myocardium adjacent to compacted myocardium in the left ventricular. The clinical presentations of this type of cardiomyopathy are of variable severity. Echocardiography used to be the diagnostic modality, but recent reports suggest that cardiac magnetic resonance imaging has higher sensitivity and specificity by showing a ratio of the noncompacted myocardium to compacted myocardium of >2.3. PMID- 26900425 TI - "Puffing" Left Atrium in a Smoker! PMID- 26900426 TI - Anatomical-botanical art. PMID- 26900427 TI - The Clinicopathologic Conference. PMID- 26900428 TI - Review of Recent Progress of Plasmonic Materials and Nano-Structures for Surface Enhanced Raman Scattering. AB - Surface-enhanced Raman scattering (SERS) has demonstrated single-molecule sensitivity and is becoming intensively investigated due to its significant potential in chemical and biomedical applications. SERS sensing is highly dependent on the substrate, where excitation of the localized surface plasmons (LSPs) enhances the Raman scattering signals of proximate analyte molecules. This paper reviews research progress of SERS substrates based on both plasmonic materials and nano-photonic structures. We first discuss basic plasmonic materials, such as metallic nanoparticles and nano-rods prepared by conventional bottom-up chemical synthesis processes. Then, we review rationally-designed plasmonic nano-structures created by top-down approaches or fine-controlled synthesis with high-density hot-spots to provide large SERS enhancement factors (EFs). Finally, we discuss the research progress of hybrid SERS substrates through the integration of plasmonic nano-structures with other nano-photonic devices, such as photonic crystals, bio-enabled nanomaterials, guided-wave systems, micro-fluidics and graphene. PMID- 26900429 TI - Fast-scan Cyclic Voltammetry for the Characterization of Rapid Adenosine Release. AB - Adenosine is a signaling molecule and downstream product of ATP that acts as a neuromodulator. Adenosine regulates physiological processes, such as neurotransmission and blood flow, on a time scale of minutes to hours. Recent developments in electrochemical techniques, including fast-scan cyclic voltammetry (FSCV), have allowed direct detection of adenosine with sub-second temporal resolution. FSCV studies have revealed a novel mode of rapid signaling that lasts only a few seconds. This rapid release of adenosine can be evoked by electrical or mechanical stimulations or it can be observed spontaneously without stimulation. Adenosine signaling on this time scale is activity dependent; however, the mode of release is not fully understood. Rapid adenosine release modulates oxygen levels and evoked dopamine release, indicating that adenosine may have a rapid modulatory role. In this review, we outline how FSCV can be used to detect adenosine release, compare FSCV with other techniques used to measure adenosine, and present an overview of adenosine signaling that has been characterized using FSCV. These studies point to a rapid mode of adenosine modulation, whose mechanism and function will continue to be characterized in the future. PMID- 26900430 TI - News in livestock research - use of Omics-technologies to study the microbiota in the gastrointestinal tract of farm animals. AB - Technical progress in the field of next-generation sequencing, mass spectrometry and bioinformatics facilitates the study of highly complex biological samples such as taxonomic and functional characterization of microbial communities that virtually colonize all present ecological niches. Compared to the structural information obtained by metagenomic analyses, metaproteomic approaches provide, in addition, functional data about the investigated microbiota. In general, integration of the main Omics-technologies (genomics, transcriptomics, proteomics and metabolomics) in live science promises highly detailed information about the specific research object and helps to understand molecular changes in response to internal and external environmental factors. The microbial communities settled in the mammalian gastrointestinal tract are essential for the host metabolism and have a major impact on its physiology and health. The microbiotas of livestock like chicken, pig and ruminants are becoming a focus of interest for veterinaries, animal nutritionists and microbiologists. While pig is more often used as an animal model for human-related studies, the rumen microbiota harbors a diversity of enzymes converting complex carbohydrates into monomers which bears high potential for biotechnological applications. This review will provide a general overview about the recent Omics-based research of the microbiota in livestock including its major findings. Differences concerning the results of pre Omics-approaches in livestock as well as the perspectives of this relatively new Omics-platform will be highlighted. PMID- 26900432 TI - Are We on the Right Track to Achieve Global Immunization Targets? Public Health Perspective. PMID- 26900433 TI - Survival Analysis for Predictive Factors of Delay Vaccination in Iranian Children. AB - BACKGROUND: Today, beside immunization coverage the age appropriate vaccination is another helpful index in public health. Evidences have shown that high immunization coverage rates do not necessarily imply age-appropriate vaccination status. The current study aimed to show the predictive factors of delayed vaccination by survival models. METHODS: A historical cohort study conducted on 3610 children aged between 24 and 47 months who was living in the suburbs of five big cities of Iran. Time of delay in vaccination of first dose of mumps-measles rubella (MMR) was calculated from date of vaccination minus age appropriate time according to vaccine card. Kaplan-Maier and Log rank tests were used for comparison the median of delay time. For controlling of confounding variables, multivariate cox model was used and hazard ratio with 95% confidence interval (95%) was reported. RESULTS: The mean +/- standard deviation and median interquartile range of delay time was 38.34 +/- 73.1 and 16 (11-31) days in delayed group. The Log rank test showed that city of living, nationality, parents' education, and birth order are related with prolonged delay time in MMR vaccination (P < 0.05). Nevertheless, child sex, prior living place (rural or city) and parent's job are not related with delay time of vaccination (P > 0.05). Cox regression showed that city of living, mother education, and nationality are the most predictive factors of delay time duration in MMR vaccination. CONCLUSIONS: Delay time duration of vaccination increased by faring from capital to the east south. Moreover, concentration of foreign immigrants in big cities and low level of mother education are the most predictors of delayed vaccination. Educational intervention should focus on immigrants and mothers with low education level. PMID- 26900431 TI - The role of purinergic receptors in stem cell differentiation. AB - A major challenge modern society has to face is the increasing need for tissue regeneration due to degenerative diseases or tumors, but also accidents or warlike conflicts. There is great hope that stem cell-based therapies might improve current treatments of cardiovascular diseases, osteochondral defects or nerve injury due to the unique properties of stem cells such as their self renewal and differentiation potential. Since embryonic stem cells raise severe ethical concerns and are prone to teratoma formation, adult stem cells are still in the focus of research. Emphasis is placed on cellular signaling within these cells and in between them for a better understanding of the complex processes regulating stem cell fate. One of the oldest signaling systems is based on nucleotides as ligands for purinergic receptors playing an important role in a huge variety of cellular processes such as proliferation, migration and differentiation. Besides their natural ligands, several artificial agonists and antagonists have been identified for P1 and P2 receptors and are already used as drugs. This review outlines purinergic receptor expression and signaling in stem cells metabolism. We will briefly describe current findings in embryonic and induced pluripotent stem cells as well as in cancer-, hematopoietic-, and neural crest-derived stem cells. The major focus will be placed on recent findings of purinergic signaling in mesenchymal stem cells addressed in in vitro and in vivo studies, since stem cell fate might be manipulated by this system guiding differentiation towards the desired lineage in the future. PMID- 26900434 TI - Assessment of Three "WHO" Patient Safety Solutions: Where Do We Stand and What Can We Do? AB - BACKGROUND: Most medical errors are preventable. The aim of this study was to compare the current execution of the 3 patient safety solutions with WHO suggested actions and standards. METHODS: Data collection forms and direct observation were used to determine the status of implementation of existing protocols, resources, and tools. RESULTS: In the field of patient hand-over, there was no standardized approach. In the field of the performance of correct procedure at the correct body site, there were no safety checklists, guideline, and educational content for informing the patients and their families about the procedure. In the field of hand hygiene (HH), although availability of necessary resources was acceptable, availability of promotional HH posters and reminders was substandard. CONCLUSIONS: There are some limitations of resources, protocols, and standard checklists in all three areas. We designed some tools that will help both wards to improve patient safety by the implementation of adapted WHO suggested actions. PMID- 26900435 TI - Low Birth Weight as a Predictor of Cardiovascular Risk Factors in Childhood and Adolescence? The PEP Family Heart Study. AB - BACKGROUND: Low birth weight is considered a risk factor for cardiovascular disease (CVD) in later life. Because data in children and adolescents are sparse and controversial, we assessed the association of birth weight with CVD risk factors in German youths. METHODS: We categorized 843 urban children and adolescents aged 3-18 years by quintiles of birth weight and measured nine traditional risk factors in terms of body mass index (BMI), waist circumference (WC), systolic (SBP) and diastolic (DBP) blood pressure, total cholesterol (TC), LDL-C, HDL-C, Non HDL-C and triglycerides (TG). SPSS 21 was used for statistical analysis. RESULTS: Mean values and prevalence of nine anthropometric and lipid risk variables were equally distributed over the five birth weight groups. Though risk factors clustered between 3.0 kg and 4.0 kg of birth weight in both genders we found only one significant correlation of birth weight with TG for males and females and another one for HDL-C in males. The strongest clustering of significant regression coefficients occurred in the 2(nd) birth weight quintile for SBP (beta 0.018), TC (beta -0.050), LDL-C (beta -0.039), non LDL-C (beta 0.049) and log TG (beta -0.001) in males and females. CONCLUSIONS: Overall we did not find significant associations between birth weight and nine traditional cardiovascular risk factors in children and adolescents. However, the 2(nd) quintile of birth weight might suggest clustering of risk factors. PMID- 26900436 TI - Body Composition in Type 2 Diabetes: Change in Quality and not Just Quantity that Matters. AB - BACKGROUND: Deranged body fat and muscle mass are aftermaths of uncontrolled diabetes. Anthropometric methods like body mass index (BMI) do not give qualitative inferences like total body fat (TBF), visceral fat (VF) or subcutaneous fat (SF) that can be given by bio-electrical impedance analysis (BIA). We studied body composition of type 2 diabetics in comparison to controls matched by age-sex, weight and BMI separately. METHODS: Seventy-eight under treatment type 2 diabetics of either sex with known glycemic and lipidemic control and equal number of controls with three patterns of matching were taken from our city. We derived parameters of body composition in both groups by Omron Karada Scan (Model HBF-510, China), using the principle of tetra poplar BIA and compared them for statistical significance. RESULTS: We found significantly more SF (30.47% +/- 7.73%), VF (11.94% +/- 4.97%) and TBF (33.96% +/- 6.07%) and significantly lesser skeletal muscle mass (23.39% +/- 4.49%) in type 2 diabetics as compared to controls, persisting even after matching with weight or BMI. On assessing qualitatively, the risk of high VF, high TBF, low skeletal muscle mass was significantly high in type 2 diabetics, which were 10.41, 3.01, 9.21 respectively for comparable BMI and 6.78, 3.51, 11.93 respectively for comparable weight. CONCLUSIONS: BIA reveals that type 2 diabetics have more ectopic fat on the expense of skeletal muscle that persists even after matching by weight or BMI, both quantitatively and qualitatively. Measurement of body composition can be included as a primary care strategy to motivate lifestyle modifications while managing metabolic derangements of type 2 diabetes. PMID- 26900437 TI - Assessment of Health Consequences of Steel Industry Welders' Occupational Exposure to Ultraviolet Radiation. AB - BACKGROUND: Welding is among the most important frequently used processes in the industry with a wide range of applications from the food industry to aerospace and from precision tools to shipbuilding. The aim of this study was to assess the level of steel industry welders' exposure to ultraviolet (UV) radiation and to investigate the health impacts of these exposures. METHODS: In this case-control study, we measured the intensity of UV at the workers' wrist in Fars Steel Company through manufacture of different types of heavy metal structures, using UV-meter model 666230 made by Leybold Co., from Germany. RESULTS: The population under the study comprised 400 people including 200 welders as the exposed group and 200 nonwelders as the unexposed group. The results of the questionnaire were analyzed using SPSS software, version 19. The average, standard deviation, maximum and minimum of the UV at the welders' wrist were 0.362, 0.346, 1.27, and 0.01 MUW/cm(2), respectively. There was a significantly (P < 0.01) higher incidence of cataracts, keratoconjunctivitis, dermatitis and erythema in welders than in their nonwelders. CONCLUSIONS: This study showed that the time period of UV exposure in welders is higher than the permissible contact threshold level. Therefore, considering the outbreak of the eye and skin disorders in the welders, decreasing exposure time, reducing UV radiation level, and using personal protective equipment seem indispensable. As exposure to UV radiation can be linked to different types of skin cancer, skin aging, and cataract, welders should be advised to decrease their occupational exposures. PMID- 26900438 TI - Effects of Administering Prophylactic Acetaminophen on Short-term Complications of Vaccination in 6-month-old Infants. AB - BACKGROUND: We aimed to assess the effects of administering prophylactic acetaminophen on short-term complications of vaccination in 6-month-old infants admitted to a private pediatric clinic in Rasht (Iran) during 2002-2013. METHODS: This quasi-experimental study was conducted on 696, infants aged 6-month-old admitted to a pediatric clinic in Rasht before vaccination during 2002-2013. Overall, 31 infants were excluded during the course of the study. While prophylactic acetaminophen was administered in 322 participants (intervention group), 343 infants (control group) received acetaminophen after vaccination. Data were collected by a checklist including complications such as fever, drowsiness, anorexia, seizure, long and excessive crying, mood change, pain, and wound at the site of injection, abscess, induration, limb swelling, and erythema. The time of occurrence of each complication was also recorded. Data were analyzed by Chi-square test in SPSS 16.0. P < 0.05 was considered significant. RESULTS: Six hundred sixty-five participants (49.6% boy) were assessed in this study. The intervention and control groups had no significant difference in terms of sex distribution (P = 0.53). Short-term complications occurred in 45% of the infants. The most common complications were erythema (24.4%), induration (19.9%), and low grade fever (16.1%). There was a significant relation between administering prophylactic acetaminophen and the incidence of low-grade fever (P = 0.01), induration (P = 0.01), and anorexia (P = 0.03). CONCLUSIONS: Our findings indicated the efficacy of prophylactic acetaminophen in reducing postvaccination complications in a population of Iranian infants. According to our findings, further research is required to determine the preferred dose and time of administering acetaminophen. PMID- 26900439 TI - Effect of Fingolimod on Platelet Count Among Multiple Sclerosis Patients. AB - BACKGROUND: While many studies have previously focused on fingolimod's effect on immune cells, the effect it has on circulating and local central nervous system platelets (Plts) has not yet been investigated. This study will elucidate what effects fingolimod treatment has on multiple sclerosis (MS) patients' plasma Plt levels. In addition, it will propose possible reasoning for these effects and suggest further investigation into this topic. METHODS: This quasi-experimental study used patients from the Isfahan Multiple Sclerosis Society to produce a subject pool of 80 patients, including 14 patients who ceased fingolimod use due to complications. The patients had their blood analyzed to determine Plt levels both 1-month prior to fingolimod treatment and 1-month after fingolimod treatment had been started. RESULTS: The mean level of Plts before initiation of fingolimod therapy (Plt1) among these MS patients was 256.53 +/- 66.26. After 1-month of fingolimod treatment, the Plt level yielded an average of 229.96 +/- 49.67 (Plt2). This number is significantly lower than the average Plt count before treatment (P < 0.01). CONCLUSIONS: MS patients taking oral fingolimod treatment may be at risk for side-effects caused by low Plt levels. This may not be a factor for patients with higher or normal Plt levels. However, a patient with naturally low Plt levels may experience a drop below the normal level and be at risk for excessive bleeding. In addition to these possible harmful side-effects, the decreased Plt population may pose positive effects for MS patients. PMID- 26900440 TI - Psychological, Social, and Familial Problems of People Living with HIV/AIDS in Iran: A Qualitative Study. AB - BACKGROUND: HIV/AIDS is one of the diseases which not only makes threats to physical health, but also, due to the negative attitudes of people and the social stigma, affects the emotional and social health of patients. The aim of this study was to identify the psychological, social, and family problems of people living with HIV/AIDS (PLWHA) in Iran. METHODS: In this qualitative study, we used purposive sampling to enroll PLWHA, their families, and physicians and consultants in two cities of Kermanshah and Tehran. Each group of PLWHA, their families, physicians, and consultants participated in two focus group discussions (FGDs), and a total of eight FGDs were conducted. Six interviews were held with all key people, individually. RESULTS: Based on the views and opinions of various groups involved in the study, the main problems of PLWHA were: Ostracism, depression, anxiety, a tendency to get revenge and lack of fear to infect others, frustration, social isolation, relationship problems, and fear due to the social stigma. Their psychological problems included: Marriage problems, family conflict, lack of family support, economic hardships inhibiting marriage, and social rejection of patient's families. Their family problems were: Unemployment, the need for housing, basic needs, homelessness, and lack of social support associations. CONCLUSIONS: It seems that the identification and focusing on psychological, social, and family problems of affected people not only is an important factor for disease prevention and control, but also enables patients to have a better response to complications caused by HIV/AIDS. PMID- 26900441 TI - Is the Use of Nutritional Supplements in Dosage Forms a "Gateway" to Oral Substance Abuse? PMID- 26900443 TI - Tuberculosis Notification by Private Sector' Physicians in Tehran. AB - BACKGROUND: A small proportion of physicians adhere to tuberculosis (TB) notification regulations, particularly in the private sector. In most developing countries, the private sector has dominance over delivering services in big cities. In such circumstances deviation from the TB treatment protocol is frequently happening. This study sought to estimate TB notification in the private sector and settle on determinants of TB notification by private sector physicians. METHODS: A population-based study has been conducted; private physicians at their clinics were interviewed. The total number of 443 private sectors' physicians has been chosen by the stratified random sampling method. Appropriate descriptive analysis was used to describe the study's participants. Logistic regression was used for bivariable and multivariable analysis. RESULTS: The response rate of the study was 90.06 (399%). Among responders, who had stated that they were suspicious of TB over the recent year, 62 (16.45%) stated that they reported cases of TB at least once during the same period. Having reporting requirements and the number of visited patients was significantly related to TB suspicious (odds ratio = 2.84, confidence interval: 1.62-5, P < 0.01). Workplace and access to relevant resources are associated with TB notification (P < 0.05). CONCLUSIONS: In poor resource settings with a high burden of TB, the public health administration can promote notification activities in the private sector by simple and quick interventions. It seems that a considerable fraction of private sector physicians, not all of them, will notify TB if they are provided with primary information and primary resources. To optimize the TB notification, however, intersectoral interventions are more likely to be successful. PMID- 26900442 TI - Preventive Role of Endothelin Antagonist on Kidney Ischemia: Reperfusion Injury in Male and Female Rats. AB - BACKGROUND: Renal ischemia/reperfusion injury (RIRI) is the most common cause of acute kidney injury. We tested the protective role of endothelin-1 receptor blocker; bosentan (BOS) in animal model of RIRI in two different genders. METHODS: Male and female Wistar rats were assigned as sham operated (sham), control group (ischemia), and case group (ischemia + BOS) treated with BOS (50 mg/kg) 2 h before bilateral kidney ischemia induced by clamping renal vessels for 45 min followed by 24 h of renal reperfusion. RESULTS: The RIRI significantly increased the serum levels of blood urea nitrogen and creatinine in both genders (P < 0.05). These values were significantly decreased by BOS in both genders. In male rats, the serum levels of malondialdehyde in the ischemia + BOS group were decreased significantly when compared with ischemia group (P < 0.05). CONCLUSIONS: BOS can be used in both genders to attenuate kidney ischemia injury possibly due to its effect in the renal vascular system. PMID- 26900444 TI - Budd-Chiari Syndrome: An Unusual Presentation of Multisystemic Sarcoidosis. AB - Sarcoidosis is a multisystem granulomatous disease of unknown origin. All organs may be affected. Liver involvement is common but it is rarely symptomatic. Only a few cases of Budd-Chiari syndrome (BCS) secondary to a hepatic sarcoidosis have been described so far. We describe a case of multisystemic sarcoidosis presenting with BCS. A 42-year old female was referred to our department for chronic and anicteric cholestasis. Laboratory and imaging investigations disclosed features of chronic BCS associated with multisystemic sarcoidosis. The positive diagnosis was based on microscopic features, which showed hepatic, gastric and cutaneous non-caseating granulomas. Screening for an underlying thrombophilic disorder was negative. The diagnosis of BCS complicating hepatic sarcoidosis was the most likely. She was put on corticosteroids and anticoagulation therapy. To our knowledge, few cases of sarcoidosis-related BCS have been reported in the literature. In addition to being an uncommon presentation of sarcoidosis, this case illustrates the importance of recognizing an unusual cause of BCS and its therapeutic difficulties. PMID- 26900445 TI - Efficient conversion of primary azides to aldehydes catalyzed by active site variants of myoglobin. AB - The oxidation of primary azides to aldehydes constitutes a convenient but underdeveloped transformation for which no efficient methods are available. Here, we demonstrate that engineered variants of the hemoprotein myoglobin can catalyze this transformation with high efficiency (up to 8,500 turnovers) and selectivity across a range of structurally diverse aryl-substituted primary azides. Mutagenesis of the 'distal' histidine residue was particularly effective in enhancing the azide oxidation reactivity of myoglobin, enabling these reactions to proceed in good to excellent yields (37-89%) and to be carried out at a synthetically useful scale. Kinetic isotope effect, isotope labeling, and substrate binding experiments support a mechanism involving heme-catalyzed decomposition of the organic azide followed by alpha hydrogen deprotonation to generate an aldimine which, upon hydrolysis, releases the aldehyde product. This work provides the first example of a biocatalytic azide-to-aldehyde conversion and expands the range of non-native chemical transformations accessible through hemoprotein-mediated catalysis. PMID- 26900446 TI - Deciphering the Mode of Action of the Processive Polysaccharide Modifying Enzyme Dermatan Sulfate Epimerase 1 by Hydrogen-Deuterium Exchange Mass Spectrometry. AB - Distinct from template-directed biosynthesis of nucleic acids and proteins, the enzymatic synthesis of heterogeneous polysaccharides is a complex process that is difficult to study using common analytical tools. Therefore, the mode of action and processivity of those enzymes are largely unknown. Dermatan sulfate epimerase 1 (DS-epi1) is the predominant enzyme during the formation of iduronic acid residues in the glycosaminoglycan dermatan sulfate. Using recombinant DS-epi1 as a model enzyme, we describe a tandem mass spectrometry-based method to study the mode of action of polysaccharide processing enzymes. The enzyme action on the substrate was monitored by hydrogen-deuterium exchange mass spectrometry and the sequence information was then fed into mathematical models with two different assumptions of the mode of action for the enzyme: processive reducing end to non reducing end, and processive non-reducing end to reducing end. Model data was scored by correlation to experimental data and it was found that DS-epi1 attacks its substrate on a random position, followed by a processive mode of modification towards the non-reducing end and that the substrate affinity of the enzyme is negatively affected by each additional epimerization event. It could also be shown that the smallest active substrate was the reducing end uronic acid in a tetrasaccharide and that octasaccharides and longer oligosaccharides were optimal substrates. The method of using tandem mass spectrometry to generate sequence information of the complex enzymatic products in combination with in silico modeling can be potentially applied to study the mode of action of other enzymes involved in polysaccharide biosynthesis. PMID- 26900447 TI - Comparative study of Hippo pathway genes in cellular conveyor belts of a ctenophore and a cnidarian. AB - BACKGROUND: The Hippo pathway regulates growth rate and organ size in fly and mouse, notably through control of cell proliferation. Molecular interactions at the heart of this pathway are known to have originated in the unicellular ancestry of metazoans. They notably involve a cascade of phosphorylations triggered by the kinase Hippo, with subsequent nuclear to cytoplasmic shift of Yorkie localisation, preventing its binding to the transcription factor Scalloped, thereby silencing proliferation genes. There are few comparative expression data of Hippo pathway genes in non-model animal species and notably none in non-bilaterian phyla. RESULTS: All core Hippo pathway genes could be retrieved from the ctenophore Pleurobrachia pileus and the hydrozoan cnidarian Clytia hemisphaerica, with the important exception of Yorkie in ctenophore. Expression study of the Hippo, Salvador and Scalloped genes in tentacle "cellular conveyor belts" of these two organisms revealed striking differences. In P. pileus, their transcripts were detected in areas where undifferentiated progenitors intensely proliferate and where expression of cyclins B and D was also seen. In C. hemisphaerica, these three genes and Yorkie are expressed not only in the proliferating but also in the differentiation zone of the tentacle bulb and in mature tentacle cells. However, using an antibody designed against the C. hemiphaerica Yorkie protein, we show in two distinct cell lineages of the medusa that Yorkie localisation is predominantly nuclear in areas of active cell proliferation and mainly cytoplasmic elsewhere. CONCLUSIONS: This is the first evidence of nucleocytoplasmic Yorkie shift in association with the arrest of cell proliferation in a cnidarian, strongly evoking the cell division-promoting role of this protein and its inhibition by the activated Hippo pathway in bilaterian models. Our results furthermore highlight important differences in terms of deployment and regulation of Hippo pathway genes between cnidarians and ctenophores. PMID- 26900449 TI - Constrained body shape among highly genetically divergent allopatric lineages of the supralittoral isopod Ligia occidentalis (Oniscidea). AB - Multiple highly divergent lineages have been identified within Ligia occidentalis sensu lato, a rocky supralittoral isopod distributed along a ~3000 km latitudinal gradient that encompasses several proposed marine biogeographic provinces and ecoregions in the eastern Pacific. Highly divergent lineages have nonoverlapping geographic distributions, with distributional limits that generally correspond with sharp environmental changes. Crossbreeding experiments suggest postmating reproductive barriers exist among some of them, and surveys of mitochondrial and nuclear gene markers do not show evidence of hybridization. Populations are highly isolated, some of which appear to be very small; thus, the effects of drift are expected to reduce the efficiency of selection. Large genetic divergences among lineages, marked environmental differences in their ranges, reproductive isolation, and/or high isolation of populations may have resulted in morphological differences in L. occidentalis, not detected yet by traditional taxonomy. We used landmark-based geometric morphometric analyses to test for differences in body shape among highly divergent lineages of L. occidentalis, and among populations within these lineages. We analyzed a total of 492 individuals from 53 coastal localities from the southern California Bight to Central Mexico, including the Gulf of California. We conducted discriminant function analyses (DFAs) on body shape morphometrics to assess morphological variation among genetically differentiated lineages and their populations. We also tested for associations between phylogeny and morphological variation, and whether genetic divergence is correlated to multivariate morphological divergence. We detected significant differences in body shape among highly divergent lineages, and among populations within these lineages. Nonetheless, neither lineages nor populations can be discriminated on the basis of body shape, because correct classification rates of cross-validated DFAs were low. Genetic distance and phylogeny had weak to no effect on body shape variation. The supralittoral environment appears to exert strong stabilizing selection and/or strong functional constraints on body shape in L. occidentalis, thereby leading to morphological stasis in this isopod. PMID- 26900448 TI - Prenatal muscle development in a mouse model for the secondary dystroglycanopathies. AB - BACKGROUND: The defective glycosylation of alpha-dystroglycan is associated with a group of muscular dystrophies that are collectively referred to as the secondary dystroglycanopathies. Mutations in the gene encoding fukutin-related protein (FKRP) are one of the most common causes of secondary dystroglycanopathy in the UK and are associated with a wide spectrum of disease. Whilst central nervous system involvement has a prenatal onset, no studies have addressed prenatal muscle development in any of the mouse models for this group of diseases. In view of the pivotal role of alpha-dystroglycan in early basement membrane formation, we sought to determine if the muscle formation was altered in a mouse model of FKRP-related dystrophy. RESULTS: Mice with a knock-down in FKRP (FKRP(KD)) showed a marked reduction in alpha-dystroglycan glycosylation and reduction in laminin binding by embryonic day 15.5 (E15.5), relative to wild type controls. In addition, the total number of Pax7(+) progenitor cells in the FKRP(KD) tibialis anterior at E15.5 was significantly reduced, and myotube cluster/myofibre size showed a significant reduction in size. Moreover, myoblasts isolated from the limb muscle of these mice at E15.5 showed a marked reduction in their ability to form myotubes in vitro. CONCLUSIONS: These data identify an early reduction of laminin alpha2, reduction of myogenicity and depletion of Pax7(+) progenitor cells which would be expected to compromise subsequent postnatal muscle growth and its ability to regenerate postnatally. These findings are of significance to the development of future therapies in this group of devastating conditions. PMID- 26900450 TI - Wolverine behavior varies spatially with anthropogenic footprint: implications for conservation and inferences about declines. AB - Understanding a species' behavioral response to rapid environmental change is an ongoing challenge in modern conservation. Anthropogenic landscape modification, or "human footprint," is well documented as a central cause of large mammal decline and range contractions where the proximal mechanisms of decline are often contentious. Direct mortality is an obvious cause; alternatively, human-modified landscapes perceived as unsuitable by some species may contribute to shifts in space use through preferential habitat selection. A useful approach to tease these effects apart is to determine whether behaviors potentially associated with risk vary with human footprint. We hypothesized wolverine (Gulo gulo) behaviors vary with different degrees of human footprint. We quantified metrics of behavior, which we assumed to indicate risk perception, from photographic images from a large existing camera-trapping dataset collected to understand wolverine distribution in the Rocky Mountains of Alberta, Canada. We systematically deployed 164 camera sites across three study areas covering approximately 24,000 km(2), sampled monthly between December and April (2007-2013). Wolverine behavior varied markedly across the study areas. Variation in behavior decreased with increasing human footprint. Increasing human footprint may constrain potential variation in behavior, through either restricting behavioral plasticity or individual variation in areas of high human impact. We hypothesize that behavioral constraints may indicate an increase in perceived risk in human modified landscapes. Although survival is obviously a key contributor to species population decline and range loss, behavior may also make a significant contribution. PMID- 26900451 TI - Disentangling vegetation diversity from climate-energy and habitat heterogeneity for explaining animal geographic patterns. AB - Broad-scale animal diversity patterns have been traditionally explained by hypotheses focused on climate-energy and habitat heterogeneity, without considering the direct influence of vegetation structure and composition. However, integrating these factors when considering plant-animal correlates still poses a major challenge because plant communities are controlled by abiotic factors that may, at the same time, influence animal distributions. By testing whether the number and variation of plant community types in Europe explain country-level diversity in six animal groups, we propose a conceptual framework in which vegetation diversity represents a bridge between abiotic factors and animal diversity. We show that vegetation diversity explains variation in animal richness not accounted for by altitudinal range or potential evapotranspiration, being the best predictor for butterflies, beetles, and amphibians. Moreover, the dissimilarity of plant community types explains the highest proportion of variation in animal assemblages across the studied regions, an effect that outperforms the effect of climate and their shared contribution with pure spatial variation. Our results at the country level suggest that vegetation diversity, as estimated from broad-scale classifications of plant communities, may contribute to our understanding of animal richness and may be disentangled, at least to a degree, from climate-energy and abiotic habitat heterogeneity. PMID- 26900452 TI - A demographic model for sex ratio evolution and the effects of sex-biased offspring costs. AB - The evolution of the primary sex ratio, the proportion of male births in an individual's offspring production strategy, is a frequency-dependent process that selects against the more common sex. Because reproduction is shaped by the entire life cycle, sex ratio theory would benefit from explicitly two-sex models that include some form of life cycle structure. We present a demographic approach to sex ratio evolution that combines adaptive dynamics with nonlinear matrix population models. We also determine the evolutionary and convergence stability of singular strategies using matrix calculus. These methods allow the incorporation of any population structure, including multiple sexes and stages, into evolutionary projections. Using this framework, we compare how four different interpretations of sex-biased offspring costs affect sex ratio evolution. We find that demographic differences affect evolutionary outcomes and that, contrary to prior belief, sex-biased mortality after parental investment can bias the primary sex ratio (but not the corresponding reproductive value ratio). These results differ qualitatively from the widely held conclusions of previous models that neglect demographic structure. PMID- 26900453 TI - FACS-style detection for real-time cell viscoelastic cytometry. AB - Cell mechanical properties have been established as a label-free biophysical marker of cell viability and health; however, real-time methods with significant throughput for accurately and non-destructively measuring these properties remain widely unavailable. Without appropriate labels for use with fluorescence activated cell sorters (FACS), easily implemented real-time technology for tracking cell-level mechanical properties remains a current need. Employing modulated optical forces and enabled by a low-dimensional FACS-style detection method introduced here, we present a viscoelasticity cytometer (VC) capable of real-time and continuous measurements. We demonstrate the utility of this approach by tracking the high-frequency cell physical properties of populations of chemically-modified cells at rates of ~ 1 s-1 and explain observations within the context of a simple theoretical model. PMID- 26900454 TI - Nanocatalyst shape and composition during nucleation of single-walled carbon nanotubes. AB - The dynamic evolution of nanocatalyst particle shape and carbon composition during the initial stages of single-walled carbon nanotube growth by chemical vapor deposition synthesis is investigated. Classical reactive and ab initio molecular dynamics simulations are used, along with environmental transmission electron microscope video imaging analyses. A clear migration of carbon is detected from the nanocatalyst/substrate interface, leading to a carbon gradient showing enrichment of the nanocatalyst layers in the immediate vicinity of the contact layer. However, as the metal nanocatalyst particle becomes saturated with carbon, a dynamic equilibrium is established, with carbon precipitating on the surface and nucleating a carbon cap that is the precursor of nanotube growth. A carbon composition profile decreasing towards the nanoparticle top is clearly revealed by the computational and experimental results that show a negligible amount of carbon in the nanoparticle region in contact with the nucleating cap. The carbon composition profile inside the nanoparticle is accompanied by a well defined shape evolution of the nanocatalyst driven by the various opposing forces acting upon it both from the substrate and from the nascent carbon nanostructure. This new understanding suggests that tuning the nanoparticle/substrate interaction would provide unique ways of controlling the nanotube synthesis. PMID- 26900456 TI - Treatment of choledochal cyst in a pediatric population. A single institution experience of 15-years. Case series. AB - BACKGROUND: Choledochal cyst (CC) is a rare congenital anomaly of the bile duct that approximately 75% of the patients are diagnosed in childhood. Without a standardized surgical procedure for the biliary reconstruction, we present our experience over the last 15 years and show the differences between the biliary reconstructions techniques in our population. METHODS: We did a retrospective hospital archive search for patients admitted to the pediatric surgery department with the diagnosis of a choledochal cyst from January 2000 to June 2015. RESULTS: We found 15 patients, of which, 1 was excluded because of missing data from the hospital record. Of the remaining 14, eight had hepaticojejunal (HY) anastomosis in Roux-en-Y, with a 25% rate of complications; six had hepatoduodenal (HD) anastomosis with a rate of complications of 16.6%. The average hospital length of stay in the group of HD vs. HY was 14 +/- 1.6-days vs. 19 +/- 8.2-days respectively. DISCUSSION: There are no standardized surgical reconstruction techniques of the biliary tract after the CC excision, there is literature that supports the biliary reconstruction with an HY and an HD without a distinct advantage over one or the other. CONCLUSION: In our series HD anastomosis represents a safe procedure with fewer complications than HY. PMID- 26900455 TI - Comparison of open gastrostomy tube to percutaneous endoscopic gastrostomy tube in lung transplant patients. AB - INTRODUCTION: Lung transplant patients require a high degree of immunosuppression, which can impair wound healing when surgical procedures are required. We hypothesized that because of impaired healing, lung transplant patients requiring gastrostomy tubes would have better outcomes with open gastrostomy tube (OGT) as compared to percutaneous endoscopic gastrostomy tube (PEG). METHODS: The National Inpatient Sample (NIS) Database (2005-2010) was queried for all lung transplant recipients requiring OGT or PEG. RESULTS: There were 215 patients requiring gastrostomy tube, with 44 OGT and 171 PEG. The two groups were not different with respect to age (52.0 vs. 56.9 years, p = 0.40) and Charlson Comorbidity Index (3.3 vs. 3.5, p = 0.75). Incidence of acute renal failure was higher in the PEG group (35.2 vs. 11.8%, p = 0.003). Post-operative pneumonia, myocardial infarction, surgical site infection, DVT/PE, and urinary tract infection were not different. Post-operative mortality was higher in the PEG group (11.2 vs. 0.0%, p = 0.02). Using multiple variable analysis, PEG tube was independently associated with mortality (HR: 1.94, 95%C.I: 1.45-2.58). Variables associated with survival included age, female gender, white race, and larger hospital bed capacity. DISCUSSION: OGT may be the preferred method of gastric access for lung transplant recipients. CONCLUSIONS: In lung transplant recipients, OGT results in decreased morbidity and mortality when compared to PEG. PMID- 26900457 TI - Impact of surgeon factor on radiocephalic fistula patency rates. AB - INTRODUCTION: Hemodialysis with arteriovenous fistula (AVF) has been widely accepted treatment modality for patients with chronic renal failure (CRF). Radiocephalic fistulas are considered to be the most desirable for the initial vascular access. The aim of this study is to investigate the surgeon factor on radiocephalic fistula patency rates. METHODS: A total of 186 patients with diagnosis of CRF underwent Radiocephalic fistula for hemodialysis access were included. Patients were divided into 2 groups according to operating surgeon. Patients were evaluated according to demographic characteristics, secondary patency rates, second AVF creation and complications. RESULTS: Mean age was 57.7 +/- 14.8 years. The most common etiology of CRF was idiopathic (66.6%). 40 (75.5%) patients in group 1 and 122 (91.7%) patients in group 2 were pre-dialysis patients (p < 0.05). Overall secondary patency rate was 77.4%. Patients in group 1 and group 2 have secondary patency rates of 83% and 75.2%, respectively (p = 0.458). Second AVF creation was done in 2 (3.8%) patients in group 1 and 23 (17.3%) patients in group 2 (p < 0.05). Postoperative complication rate was 9.6%. CONCLUSION: Operating surgeon is not a major factor of secondary patency in radiocephalic arteriovenous fistulas. PMID- 26900458 TI - Surgical approach and technique in retrosternal goiter: Case report and review of the literature. AB - BACKGROUND: Retrosternal goiter is defined as a thyroid mass of which more than 50% is located below the thoracic inlet. The aim of this study is to assess the retrosternal goiter surgically approach through a neck incision and analyze the surgical technique. CASE PRESENTATION: The case reported by us used a single neck collar-shaped incision for huge retrosternal goiter with good outcome. The patient was surgically treated through a neck incision without the need for sternotomy or lateral thoracotomy. We did not observe definitive lesions in the inferior laryngeal nerve or definitive hypoparathyroidism. CONCLUSIONS: Patients with retrosternal goiter can be safely treated surgically through a single neck incision, which is less trauma and recovery quickly. PMID- 26900459 TI - The surgery for blue rubber bleb nevus syndrome. AB - Blue rubber bleb nevus syndrome (BRBNS) is a rare vascular anomaly syndrome consisting of multifocal venous malformations (VM). The malformations are most. prominent in the skin, soft tissues and gastrointestinal (GI) tract. Chronic bleeding induced by the vascular malformation (VM) lesions in gastrointestinal (GI) tract was the main clinical problem which should be treated. In this paper, two patients with BRBNS were treated by surgery for gastrointestinal bleeding. Our results indicated the endoscope examination was the best diagnostic way for VM in GI. Although many therapeutic methods have been tried, aggressive surgical eradication was the most effective for venous anomalies that cause GI bleeding in BRBNS. PMID- 26900460 TI - Peri-colonic haematoma following routine colonoscopy. AB - INTRODUCTION: We present a case of an extra-luminal haematoma following routine colonoscopy. This case highlights an uncommon but potentially life threatening complication in which there is little published literature to date. PRESENTATION OF CASE: A 73 year old male presented with abdominal pain and a reduction in haemoglobin following an uneventful colonoscopy. The imaging had been required as part of colorectal cancer follow up. Initial differential diagnosis included colonic perforation and the patient was admitted for further investigations. Same day CT scan imaging revealed an extra-luminal haematoma in the mid descending colon. The patient was managed non-operatively and was discharged with antibiotics following a period of observation. DISCUSSION: Colonoscopy is a highly effective imaging modality for direct visualisation of the lower gastrointestinal tract and for simultaneous diagnostic or therapeutic interventions. In recent years the use of colonoscopy has increased greatly, this is largely due to an increasingly aging population, increased availability of the resource and as a consequence of the implementation of the Bowel Cancer Screening Programme. Extra-colonic bleeding following colonoscopy is rare. Causes that have been identified in the literature include splenic injury, mesenteric tears, hepatic injury and retroperitoneal haemorrhage. To the authors' knowledge, there is very little published literature specifically on isolated peri-colonic haematomas following colonoscopy. CONCLUSION: This case highlights an unusual but potentially life threatening complication following colonoscopy. Endoscopists and clinicians should be aware of the diagnosis to allow for early recognition and appropriate management. PMID- 26900461 TI - Peritoneal mesothelioma metastasis to the tongue - Comparison with 8 pleural mesothelioma reports with tongue metastases. AB - PURPOSE: Malignant mesothelioma (MM) rarely arises from the peritoneum. We describe the 1st such case which metastasised to the head and neck region (tongue). METHODS: We briefly surveyed the American Surveillance Epidemiology and End Results (SEER) database, and the British Cancer Research UK database for the latest trends in MM incidence. We did a systematic Pubmed search for other MM reports with tongue metastases. RESULTS AND PRESENTATION OF CASE: American and British data show that MM incidence in men has stabilised in the last 10 years, earlier than previously predicted. The tongue is an unusual site for MM spread, with ours being only the 9th such case described. Our summary of published cases of MM metastasising to the tongue brings out our patient to be the least in age(35 years), and the only one to have peritoneal MM as the primary. Seven of the 9 cases were male. Only 2 had a recorded history of exposure to asbestos. All 9 patients had the epithelioid subtype of MM. Surgery was done as the exclusive reported intervention in 4 out of the 9 patients. Only 2 cases received radiotherapy, amongst whom, only our patient responded. CONCLUSIONS: Metastasis of MM to the tongue is rare and usually in the uncommon context of MM with multiple sites of extra-thoracic or extra-abdominal spread. We have described a unique clinical manifestation of a rare subtype of mesothelioma. Moreover, we have tabulated and summarised details (including responses to surgery or/and radiotherapy) regarding all reported cases of mesotheliomas with tongue metastasis. PMID- 26900462 TI - Avascular necrosis of the femoral head at 2 years after pertrochanteric fracture surgery: Case report. AB - INTRODUCTION: The avascular necrosis of the femoral head represents the death of bone tissue due to the lack of blood supply. The disease has a progressive evolution and left untreated leads to femoral head collapse and severe arthritis. CASE PRESENTATION: We present a case of a pertrochanteric fracture which has been successfully operated with a dynamic interlocking trochanteric gamma nail on the right hip. At 2 years after surgery the patient developed an incipient avascular necrosis of the femoral head. Despite the good positioning of the implant, we considered that the source of the pain was an intolerance of the implant, and thus we removed it. After implant removal, the patient was kept under observation and conservative treatment, to prevent further damage to the right hip and allow the healing to occur. At 6 months after the gamma nail was removed the X-rays revealed advanced avascular necrosis of the femoral head and secondary osteoarthritis on the right hip. The patient underwent surgery with an uncemented total hip arthroplasty. DISCUSSION: There are a few discussions regarding the avascular necrosis of the femoral head. These discussions may include the predisposing risk factors, the treatment of choice and the postoperative complications. CONCLUSION: The avascular necrosis of the femoral head is a complication of pertrochanteric fractures that can not be foreseen or avoided. The optimal treatment in these cases is uncemented total hip arthroplasty. PMID- 26900463 TI - Traumatic partial amputation of the tongue. Case report and literature review. AB - INTRODUCTION: The traumatic injuries to the tongue can go form section to partial or complete amputation, the latter being a rare presentation in the setting of facial trauma or even in patients with mental illness. CASE REPORT: We present 25 year-old patient with traumatic partial amputation of the tongue who presented to the emergency department with successful surgical repair with good functional and esthetic outcome. DISCUSSION: The tongue can suffer a broad type of traumatic injuries, in the setting of active bleeding, the muscular planes must be closed with absorbable sutures to stop the hemorrhage and prevent hematoma formation. Tongue surgical repair in the setting of a total section requires integrity of arterial and venous flow, so anastomosis must be executed. CONCLUSION: Amputation of the tongue can put the patient's life at risk and its management needs to be mastered by the surgeons treating polytraumatized patients. PMID- 26900464 TI - Small cell neuroendocrine carcinoma of the endometrium with pulmonary metastasis: A clinicopathologic study of a case and a brief review of the literature. AB - Neuroendocrine carcinomas (NEC) of the female genital tract are aggressive and rare tumors that usually involve the cervix and ovary, and are seen rarely in the endometrium in perimenopausal or postmenopausal women. We presented a case of a73 year-old postmenopausal woman with vaginal bleeding and abdominal pain. A subsequent computerized tomography (CT) scan of pelvis showed an enlarged uterus (20,0 * 12,0 cm) with para-aortic and pelvic lymph node metastases. She underwent surgical debulking and staging of an endometrial tumor with omental metastasis and positive lymph nodes. The pathological diagnosis was primary small cell carcinoma (SCC) combined with endometrioid carcinoma of uterine corpus. Her final FIGO stage was IVB. Three months after surgery CT-total body showed a metastasis to left lung of SCC. Because the small-cell component of endometrial tumor showed a strong positivity for TTF1 as pulmonary counterpart a differential diagnosis with a primary small cell carcinoma of the lung should be made. Identifying an appropriate therapeutic management for SCC of endometrium is challenging since these are extremely rare tumors. An optimal initial therapeutic approach to this rare disease, especially at an advanced stage, has not yet been clearly defined. However, in these a multidisciplinary therapy, including surgery, chemotherapy, and radiotherapy represent until this time the only therapeutic option. PMID- 26900465 TI - Association of H-FABP gene polymorphisms with intramuscular fat content in Three yellow chickens and Hetian-black chickens. AB - BACKGROUND: To explore the relationship between the heart-type fatty acid binding protein (H-FABP) gene and intramuscular fat (IMF), a polymorphism of the second exon of the H-FABP gene was investigated in 60 Three-yellow chickens (TYCs) and 60 Hetian-black chickens (HTBCs). RESULTS: The IMF contents of the cardiac, chest and leg muscles in HTBC were increased compared with TYC. Both TYC and HTBC populations exhibited Hardy-Weinberg Equilibrium (HWE) according to the chi(2) test. Three variations of the two birds were detected, namely, G939A, G982A and C1014T. HTBCs with the TT genotypes exhibit increased IMF content in the chest muscles compared with the TC genotype. Thus, the G982A site could be considered a genetic marker for selecting increased IMF content in the chest muscles of HTBC. The correlation coefficients revealed that H-FABP mRNA expression was negatively correlated with the IMF content in the cardiac, chest and leg muscles of HTBC and in the cardiac and chest muscles of TYC. The relative mRNA expression of H-FABP was reduced in the cardiac and leg muscles of HTBC compared with TYC, but this difference was not observed at the protein level, as assessed by Western blot analysis. CONCLUSIONS: These findings offer essential data that can be useful in the breeding program of HTBC and future research exploring the role of H-FABP in IMF deposition and regulation in chickens. PMID- 26900467 TI - Intake, digestibility and nitrogen utilization in cattle fed tropical forage and supplemented with protein in the rumen, abomasum, or both. AB - BACKGROUND: There is little information in the tropics with regard the comparative understanding of how an increased nitrogen supply in the rumen or in the intestines affects efficiency of nitrogen utilization in cattle. This study evaluated the effects of supplementation with nitrogenous compounds in the rumen, abomasum, or both on intake, digestibility and the characteristics of nitrogen utilization in cattle fed tropical forage. Four rumen- and abomasum-fistulated Nellore bulls (227 +/- 11 kg) were used. Four treatments were evaluated: control, ruminal supplementation (230 g/d of supplemental protein in the rumen), abomasal supplementation (230 g/d of supplemental protein in the abomasum), and ruminal and abomasal supplementation (115 g/d protein in both the rumen and the abomasum). The basal forage diet consisted of Tifton 85 hay with a crude protein (CP) level of 78.4 g/kg dry matter. Casein was used as a supplement. The experiment was conducted using a 4 * 4 Latin square. RESULTS: There were no differences between the treatments (P > 0.10) with regard to forage intake. The intake and total digestibility of CP increased (P < 0.01) with supplementation. The nitrogen balance in the body increased (P < 0.01) and muscle protein mobilization decreased (P < 0.01) with supplementation, regardless of the supplementation site. The efficiency of nitrogen utilization did not differ among the treatments (P > 0.10). CONCLUSIONS: The supplementation of cattle fed tropical forage with protein in the rumen, abomasum, or both similarly increased the nitrogen accretion in animal, which reflects improvements on nitrogen status in animal body. PMID- 26900466 TI - Cellular reprogramming in farm animals: an overview of iPSC generation in the mammalian farm animal species. AB - Establishment of embryonic stem cell (ESC) lines has been successful in mouse and human, but not in farm animals. Development of direct reprogramming technology offers an alternative approach for generation of pluripotent stem cells, applicable also in farm animals. Induced pluripotent stem cells (iPSCs) represent practically limitless, ethically acceptable, individuum-specific source of pluripotent cells that can be generated from different types of somatic cells. iPSCs can differentiate to all cell types of an organism's body and have a tremendous potential for numerous applications in medicine, agriculture, and biotechnology. However, molecular mechanisms behind the reprogramming process remain largely unknown and hamper generation of bona fide iPSCs and their use in human clinical practice. Large animal models are essential to expand the knowledge obtained on rodents and facilitate development and validation of transplantation therapies in preclinical studies. Additionally, transgenic animals with special traits could be generated from genetically modified pluripotent cells, using advanced reproduction techniques. Despite their applicative potential, it seems that iPSCs in farm animals haven't received the deserved attention. The aim of this review was to provide a systematic overview on iPSC generation in the most important mammalian farm animal species (cattle, pig, horse, sheep, goat, and rabbit), compare protein sequence similarity of pluripotency-related transcription factors in different species, and discuss potential uses of farm animal iPSCs. Literature mining revealed 32 studies, describing iPSC generation in pig (13 studies), cattle (5), horse (5), sheep (4), goat (3), and rabbit (2) that are summarized in a concise, tabular format. PMID- 26900468 TI - Integration of omics: more than the sum of its parts. AB - Genome scale data on biological systems has increasingly become available by sequencing of DNA and RNA, and by mass spectrometric quantification of proteins and metabolites. The cellular components from which these -omics regimes are derived act as one integrated system in vivo; thus, there is a natural instinct to integrate -omics data types. Statistical analyses, the use of previous knowledge in the form of networks, and the use of time-resolved measurements are three key design elements for life scientists to consider in planning integrated omics studies. These design elements are reviewed in the context of multiple recent systems biology studies that leverage data from different types of -omics analyses. While most of these studies rely on well-established model organisms, the concepts for integrating -omics data that were developed in these studies can help to enable systems research in the field of cancer biology. PMID- 26900469 TI - Differentiation of human monocytes and derived subsets of macrophages and dendritic cells by the HLDA10 monoclonal antibody panel. AB - The mononuclear phagocyte system, consisting of monocytes, macrophages and dendritic cells (DCs), has an important role in tissue homeostasis as well as in eliciting immune responses against invading pathogens. Blood monocytes have been viewed for decades as precursors of tissue macrophages. Although the newest data show that in the steady state resident macrophages of many organs are monocyte independent, blood monocytes critically contribute to tissue macrophage and DC pools upon inflammation. To better understand the relationship between these populations and their phenotype, we isolated and differentiated human blood CD14(+) monocytes in vitro into immature and mature monocyte-derived dendritic cells (MoDCs) as well as into seven different monocyte-derived macrophage subsets. We used the panel of 70 monoclonal antibodies (mAbs) submitted to the 10th Human Leukocyte Differentiation Antigen Workshop to determine the expression profiles of these 10 populations by flow cytometry. We now can compile subpanels of mAbs to differentiate the 10 monocyte/macrophage/MoDC subsets, providing the basis for novel diagnostic and therapeutic tools. PMID- 26900470 TI - Treg activation defect in type 1 diabetes: correction with TNFR2 agonism. AB - Activated T-regulatory cells (aTregs) prevent or halt various forms of autoimmunity. We show that type 1 diabetics (T1D) have a Treg activation defect through an increase in resting Tregs (rTregs, CD4(+)CD25(+)Foxp3(+)CD45RA) and decrease in aTregs (CD4(+)CD25(+)Foxp3(+)CD45RO) (n= 55 T1D, n=45 controls, P=0.01). The activation defect persists life long in T1D subjects (T1D=45, controls=45, P=0.01, P=0.04). Lower numbers of aTregs had clinical significance because they were associated with a trend for less residual C-peptide secretion from the pancreas (P=0.08), and poorer HbA1C control (P=0.03). In humans, the tumor necrosis factor receptor 2 (TNFR2) is obligatory for Treg induction, maintenance and expansion of aTregs. TNFR2 agonism is a method for stimulating Treg conversion from resting to activated. Using two separate in vitro expansion protocols, TNFR2 agonism corrected the T1D activation defect by triggering conversion of rTregs into aTregs (n=54 T1D, P<0.001). TNFR2 agonism was superior to standard protocols and TNF in proliferating Tregs. In T1D, TNFR2 agonist expanded Tregs were homogeneous and functionally potent by virtue of suppressing autologous cytotoxic T cells in a dose-dependent manner comparable to controls. Targeting the TNFR2 receptor for Treg expansion in vitro demonstrates a means to correct the activation defect in T1D. PMID- 26900471 TI - Nomenclature of CD molecules from the Tenth Human Leucocyte Differentiation Antigen Workshop. PMID- 26900472 TI - Common variable immunodeficiency associated with microdeletion of chromosome 1q42.1-q42.3 and inositol 1,4,5-trisphosphate kinase B (ITPKB) deficiency. AB - Common variable immunodeficiency (CVID) is a heterogenous disorder characterized by hypogammaglobulinemia and impaired specific antibody response and increased susceptibility to infections, autoimmunity and malignancies. A number of gene mutations, including ICOS, TACI and BAFF-R, and CD19, CD20, CD21, CD81, MSH5 and LRBA have been described; however, they account for approximately 20-25% of total cases of CVID. In this study, we report a patient with CVID with an intrinsic microdeletion of chromosome 1q42.1-42.3, where gene for inositol 1,3,4, trisphosphate kinase beta (ITPKB) is localized. ITPKB has an important role in the development, survival and function of B cells. In this subject, the expression of ITPKB mRNA as well as ITKPB protein was significantly reduced. The sequencing of ITPKB gene revealed three variants, two of them were missense variants and third was a synonymous variant; the significance of each of them in relation to CVID is discussed. This case suggests that a deficiency of ITPKB may have a role in CVID. PMID- 26900474 TI - New insights into the phenotype of human dendritic cell populations. AB - HLDA10 is the Tenth Human Leukocyte Differentiation Antigen (HLDA) Workshop. The HLDA Workshops provide a mechanism to allocate cluster of differentiation (CD) nomenclature by engaging in interlaboratory studies. As the host laboratory, we invited researchers from national and international academic and commercial institutions to submit monoclonal antibodies (mAbs) to human leukocyte surface membrane molecules, particularly those that recognised molecules on human myeloid cell populations and dendritic cells (DCs). These mAbs were tested for activity and then distributed as a blinded panel to 15 international laboratories to test on different leukocyte populations. These populations included blood DCs, skin derived DCs, tonsil leukocytes, monocyte-derived DCs, CD34-derived DCs, macrophage populations and diagnostic acute myeloid leukaemia and lymphoma samples. Each laboratory was provided with enough mAb to perform five repeat experiments. Here, we summarise the reactivity of different mAb to 68 different cell-surface molecules expressed by human myeloid and DC populations. Submitted mAbs to some of the molecules were further validated to collate data required to designate a formal CD number. This collaborative process provides the broader scientific community with an invaluable data set validating mAbs to leukocyte surface molecules. PMID- 26900473 TI - Oral immune therapy: targeting the systemic immune system via the gut immune system for the treatment of inflammatory bowel disease. AB - Inflammatory bowel diseases (IBD) are associated with an altered systemic immune response leading to inflammation-mediated damage to the gut and other organs. Oral immune therapy is a method of systemic immune modulation via alteration of the gut immune system. It uses the inherit ability of the innate system of the gut to redirect the systemic innate and adaptive immune responses. Oral immune therapy is an attractive clinical approach to treat autoimmune and inflammatory disorders. It can induce immune modulation without immune suppression, has minimal toxicity and is easily administered. Targeting the systemic immune system via the gut immune system can serve as an attractive novel therapeutic method for IBD. This review summarizes the current data and discusses several examples of oral immune therapeutic methods for using the gut immune system to generate signals to reset systemic immunity as a treatment for IBD. PMID- 26900477 TI - A robust prognostic gene expression signature for early stage lung adenocarcinoma. AB - BACKGROUND: Stage I lung adenocarcinoma is usually not treated with adjuvant chemotherapy; however, around half of these patients do not survive 5 years. Therefore, a reliable prognostic biomarker for early stage patients would be critical to identify those most likely to benefit from early additional treatments. Several studies have searched for gene expression prognostic biomarkers for lung adenocarcinoma, but these have not yielded a widely accepted prognosticator. RESULTS: We analyzed gene expression from seven published lung adenocarcinoma cohorts for which we included only stage I and II patients who were not given adjuvant therapy. Seven genes consistently obtained statistical significance in Cox regression for overall survival. The combined signature has a weighted mean hazard ratio of 3.2 in all cohorts and 3.0 (C.I. 1.3-7.4, p < 0.01) in an independent validation cohort and is strongly correlated with previously published signatures of chromosomal instability and cell cycle progression. CONCLUSIONS: The new prognostic signature, if validated prospectively, may enable better stratification and treatment of early stage lung cancer patients. PMID- 26900475 TI - Histone deacetylases in monocyte/macrophage development, activation and metabolism: refining HDAC targets for inflammatory and infectious diseases. AB - Macrophages have central roles in danger detection, inflammation and host defense, and consequently, these cells are intimately linked to most disease processes. Major advances in our understanding of the development and function of macrophages have recently come to light. For example, it is now clear that tissue resident macrophages can be derived from either blood monocytes or through local proliferation of phagocytes that are originally seeded during embryonic development. Metabolic state has also emerged as a major control point for macrophage activation phenotypes. Herein, we review recent literature linking the histone deacetylase (HDAC) family of enzymes to macrophage development and activation, particularly in relation to these recent developments. There has been considerable interest in potential therapeutic applications for small molecule inhibitors of HDACs (HDACi), not only for cancer, but also for inflammatory and infectious diseases. However, the enormous range of molecular and cellular processes that are controlled by different HDAC enzymes presents a potential stumbling block to clinical development. We therefore present examples of how classical HDACs control macrophage functions, roles of specific HDACs in these processes and approaches for selective targeting of drugs, such as HDACi, to macrophages. Development of selective inhibitors of macrophage-expressed HDACs and/or selective delivery of pan HDACi to macrophages may provide avenues for enhancing efficacy of HDACi in therapeutic applications, while limiting unwanted side effects. PMID- 26900478 TI - Reliability of the Q Force; a mobile instrument for measuring isometric quadriceps muscle strength. AB - BACKGROUND: The ability to generate muscle strength is a pre-requisite for all human movement. Decreased quadriceps muscle strength is frequently observed in older adults and is associated with a decreased performance and activity limitations. To quantify the quadriceps muscle strength and to monitor changes over time, instruments and procedures with a sufficient reliability are needed. The Q Force is an innovative mobile muscle strength measurement instrument suitable to measure in various degrees of extension. Measurements between 110 and 130 degrees extension present the highest values and the most significant increase after training. The objective of this study is to determine the test retest reliability of muscle strength measurements by the Q Force in older adults in 110 degrees extension. METHODS: Forty-one healthy older adults, 13 males and 28 females were included in the study. Mean (SD) age was 81.9 (4.89) years. Isometric muscle strength of the Quadriceps muscle was assessed with the Q Force at 110 degrees of knee extension. Participants were measured at two sessions with a three to eight day interval between sessions. To determine relative reliability, the intraclass correlation coefficient (ICC) was calculated. To determine absolute reliability, Bland and Altman Limits of Agreement (LOA) were calculated and t-tests were performed. RESULTS: Relative reliability of the Q Force is good to excellent as all ICC coefficients are higher than 0.75. Generally a large 95 % LOA, reflecting only moderate absolute reliability, is found as exemplified for the peak torque left leg of -18.6 N to 33.8 N and the right leg of -9.2 N to 26.4 N was between 15.7 and 23.6 Newton representing 25.2 % to 39.9 % of the size of the mean. Small systematic differences in mean were found between measurement session 1 and 2. CONCLUSION: The present study shows that the Q Force has excellent relative test-retest reliability, but limited absolute test-retest reliability. Since the Q Force is relatively cheap and mobile it is suitable for application in various clinical settings, however, its capability to detect changes in muscle force over time is limited but comparable to existing instruments. PMID- 26900479 TI - Mercury pollution for marine environment at Farwa Island, Libya. AB - BACKGROUND: Farwa is an Island in Libya receives petrochemical wastes generated from General Company of Chemical Industries (GCCI) since more than 40 years. AIM: The present work aimed to determine the concentrations of mercury (Hg(+2)) in fish, marine plants and sediment collected from Farwa lagoon to evaluate effect of industrial wastewater from GCCI on the marine environment. METHODS: Hundred and twelve samples of fish, pearl oyster, cuttlefish sediments and marine plants were analyzed to determine Hg(2+) concentration during the period from January to August 2014 by using Atomic Absorption Spectrometer (AAS). RESULTS: The highest concentration of Hg(2+) was detected in Pinctada radiata (11.67 +/- 3.30 MUgg ( 1)) followed by Serranus scriba (6.37 +/- 0.11 MUg g (-1)) and Epinephelus marginatus (6.19 +/- 0.02 MUg g (-1)). About 75 % of marine plants contained the maximum contaminations during the summer season. In fish samples Hg(2+) concentrations exceeded the levels provided by international standards. CONCLUSIONS: The fish at Farwa lagoon is heavily contaminated with Hg(2+) which may represent a source for mercury poisoning for human. PMID- 26900481 TI - Effects of season and age at first calving on genetic and phenotypic characteristics of lactation curve parameters in Holstein cows. AB - In this research data representing 72,946 primiparous cows from 724 herds with 638,063 total test day records calved between 2001 and 2011. These data were analysed to determine the effect of age at first and season of calving on parameters of the Wood lactation curve. Also, genetic trend of the lactation curve parameters in different calving years were evaluated. The results indicate that the highest rate of atypical lactation curve was related to cows that calved in summer (28.05 %). The maximum phenotypic relationship between initial milk yield and total 305-d milk yield was observed in cows calved in spring (0.40). The role of peak yield is more than peak time on 305-d total milk yield in primiparous Holstein. One month increase in age at first calving from 18 to 26 month raised 305-d milk yield by around 138 kg and from 27 to 32 month decreased by 61 kg. The persistency of lactation between 101 and 200 days is higher than that of 201-305 days. Our results indicate that the shape of lactation curve is largely dependent on the season of calving (higher level of milk production in cows which calved in autumn and winter). The heritabilities of parameters of lactation curve and persistency measures were low. The genetic trends for peak time, peak yield and 305-d milk yields were positive and estimated to be 0.019, 0.021 and 8.13 kg/year respectively. So the range from 24 to 26.5 month of calving is the optimum calving time in primiparous Holstein for maximizing 305-d milk yield. PMID- 26900480 TI - Anxiety, coping skills and hypothalamus-pituitary-adrenal (HPA) axis in patients with endometriosis. AB - BACKGROUND: Endometriosis is an inflammatory disease that is defined by growth of endometrial tissue outside the uterus, resulting in pain, infertility, and emotional distress. Previous studies have shown that the HPA axis is compromised in patients with chronic, painful diseases, including endometriosis. However, the underlying mechanisms and the physiological and emotional consequences of dysfunctions in the HPA axis in these patients are largely unknown. We aimed to understand whether diurnal circulating cortisol levels in women with endometriosis are affected and how this impacts their emotional and behavioral responses. METHODS: Thirty-two patients with endometriosis and 36 healthy control women provided saliva samples and completed a series of psychological questionnaires. Salivary cortisol levels were measured in duplicate using a colorimetric immunoassay. RESULTS: There were significant differences in average cortisol levels between endometriosis patients and controls. A negative correlation was found between cortisol levels and infertility and dyspareunia. Furthermore, incapacitating pain was found to be a strong predictor of hypocortisolism. Women with endometriosis reported higher levels of trait anxiety, but showed no differences in perceived stress or in coping styles compared to the control group. CONCLUSIONS: This study supports previous reports of hypocortisolism as a biomarker of aberrant HPA responses in women with endometriosis. Moreover, it provides further insight into the link between HPA axis dysregulation, emotional responses, and the high comorbidity between endometriosis and other inflammatory conditions. PMID- 26900482 TI - Erratum to: Investigation of the changes of biophysical/mechanical characteristics of differentiating preosteoblasts in vitro. AB - [This corrects the article DOI: 10.1186/s40824-015-0046-y.]. PMID- 26900483 TI - Bivalve-specific gene expansion in the pearl oyster genome: implications of adaptation to a sessile lifestyle. AB - INTRODUCTION: Bivalve molluscs have flourished in marine environments, and many species constitute important aquatic resources. Recently, whole genome sequences from two bivalves, the pearl oyster, Pinctada fucata, and the Pacific oyster, Crassostrea gigas, have been decoded, making it possible to compare genomic sequences among molluscs, and to explore general and lineage-specific genetic features and trends in bivalves. In order to improve the quality of sequence data for these purposes, we have updated the entire P. fucata genome assembly. RESULTS: We present a new genome assembly of the pearl oyster, Pinctada fucata (version 2.0). To update the assembly, we conducted additional sequencing, obtaining accumulated sequence data amounting to 193* the P. fucata genome. Sequence redundancy in contigs that was caused by heterozygosity was removed in silico, which significantly improved subsequent scaffolding. Gene model version 2.0 was generated with the aid of manual gene annotations supplied by the P. fucata research community. Comparison of mollusc and other bilaterian genomes shows that gene arrangements of Hox, ParaHox, and Wnt clusters in the P. fucata genome are similar to those of other molluscs. Like the Pacific oyster, P. fucata possesses many genes involved in environmental responses and in immune defense. Phylogenetic analyses of heat shock protein70 and C1q domain-containing protein families indicate that extensive expansion of genes occurred independently in each lineage. Several gene duplication events prior to the split between the pearl oyster and the Pacific oyster are also evident. In addition, a number of tandem duplications of genes that encode shell matrix proteins are also well characterized in the P. fucata genome. CONCLUSIONS: Both the Pinctada and Crassostrea lineages have expanded specific gene families in a lineage-specific manner. Frequent duplication of genes responsible for shell formation in the P. fucata genome explains the diversity of mollusc shell structures. These duplications reveal dynamic genome evolution to forge the complex physiology that enables bivalves to employ a sessile lifestyle in the intertidal zone. PMID- 26900484 TI - Association between insufficient medication of antihypertensives and the severity of acute ischemic stroke. AB - BACKGROUND: Although recent studies have suggested that adherence to antihypertensive treatment reduced stroke incidence, the relationship of adherence to antihypertensives with stroke severity has not been studied. This study attempted to know whether nonadherence before stroke is associated with initial severity of acute ischemic stroke. METHODS: Consecutive patients with acute ischemic stroke were identified in Soonchunhyang University Hospital from Mar 2005 to Aug 2014, excluding the cases without hypertension or information of antihypertensive adherence. We compared the mean of National Institute of Health Stroke Scale (NIHSS) score between adherence groups and insufficient medication group, and additionally in each stroke subtype. Multiple linear regression model was established for initial NIHSS score adjusting alleged factors linked to stroke severity. RESULTS: Initial NIHSS score were higher in insufficient medication group than adherence group (6.5 +/- 7.2 VS 5.4 +/- 5.7, P = .11). In large artery atherosclerosis (LAA) and small vessel occlusion (SVO), initial NIHSS score were significantly higher in insufficient medication group (6.1 +/- 6.5 VS 4.4 +/- 4.4, P = .004 for LAA; 3.8 +/- 3.5 VS 2.7 +/- 1.8, P = .014 for SVO). In multiple linear regression model, insufficient medication to antihypertensives had a significant effect on NIHSS score (t = 3.417, P = .001) after adjusting covariates. CONCLUSION: Insufficient medication of antihypertensives before stroke was independently associated with the severity of acute ischemic stroke. Further studies with prospective designs are warranted to evaluate clinical implication of adherence to antihypertensives for ischemic stroke. PMID- 26900486 TI - Dyadic Adjustment and Spiritual Activities in Parents of Children with Cystic Fibrosis. AB - Children's diseases can negatively impact marital adjustment and contribute to poorer child health outcomes. To cope with increased marital stress and childhood diseases severity, many people turn to spirituality. While most studies show a positive relationship between spirituality and marital adjustment, spirituality has typically been measured only in terms of individual behaviors. Using the Dyadic Adjustment Scale (DAS) and Daily Phone Diary data from a sample of 126 parents of children with cystic fibrosis as a context for increased marital stress, spiritual behavior of mother-father dyads and of whole families were used as predictors of marital adjustment. Frequency and duration of individual, dyadic and familial spiritual activities correlated positively with dyadic adjustment. Significant differences in spiritual activities existed between couples with marital adjustment scores above and below the cutoff for distress. The only significant factors in regressions of spiritual activities on marital adjustment scores were number of pulmonary exacerbations and parent age. Higher odds of maintaining a marital adjustment score greater than 100 were significantly associated with spending approximately twelve minutes per day in individual, but not conjugal or familial, spiritual activities. The Daily Phone Diary is a feasible tool to study conjugal and familial activities and their relationships with beliefs and attitudes, including spirituality. PMID- 26900487 TI - DataSpread: Unifying Databases and Spreadsheets. AB - Spreadsheet software is often the tool of choice for ad-hoc tabular data management, processing, and visualization, especially on tiny data sets. On the other hand, relational database systems offer significant power, expressivity, and efficiency over spreadsheet software for data management, while lacking in the ease of use and ad-hoc analysis capabilities. We demonstrate DataSpread, a data exploration tool that holistically unifies databases and spreadsheets. It continues to offer a Microsoft Excel-based spreadsheet front-end, while in parallel managing all the data in a back-end database, specifically, PostgreSQL. DataSpread retains all the advantages of spreadsheets, including ease of use, ad hoc analysis and visualization capabilities, and a schema-free nature, while also adding the advantages of traditional relational databases, such as scalability and the ability to use arbitrary SQL to import, filter, or join external or internal tables and have the results appear in the spreadsheet. DataSpread needs to reason about and reconcile differences in the notions of schema, addressing of cells and tuples, and the current "pane" (which exists in spreadsheets but not in traditional databases), and support data modifications at both the front-end and the back-end. Our demonstration will center on our first and early prototype of the DataSpread, and will give the attendees a sense for the enormous data exploration capabilities offered by unifying spreadsheets and databases. PMID- 26900485 TI - Epigenetics-a potential mediator between air pollution and preterm birth. AB - Preterm birth is a major cause of infant morbidity and mortality and a potential risk factor for adult chronic disease. With over 15 million infants born preterm worldwide each year, preterm birth poses a global health concern. There is a possible association between air pollution and preterm birth, though studies have been inconsistent, likely due to variation in study design. How air pollution induces health effects is uncertain; however, studies have repeatedly demonstrated the effects of air pollution on epigenetic modifications. More recent evidence suggests that epigenetics may, in turn, be linked to preterm birth. Discovery of environmentally modifiable epigenetic processes connected to preterm birth may help to identify women at risk of preterm birth, and ultimately lead to development of new preterm birth prevention measures. PMID- 26900488 TI - Mechanistic Studies of epsilon-Caprolactone Polymerization by (salen)AlOR Complexes and a Predictive Model for Cyclic Ester Polymerizations. AB - Aluminum alkoxide complexes (2) of salen ligands with a three-carbon linker and para substituents having variable electron-withdrawing capabilities (X = NO2, Br, OMe) were prepared, and the kinetics of their ring-opening polymerization (ROP) of epsilon-caprolactone (CL) were investigated as a function of temperature, with the aim of drawing comparisons to similar systems with two-carbon linkers investigated previously (1). While 1 and 2 exhibit saturation kinetics and similar dependences of their ROP rates on substituents X (invariant Keq, similar Hammett rho = +1.4(1) and 1.2(1) for k2, respectively), ROP by 2 was significantly faster than for 1. Theoretical calculations confirm that, while the reactant structures differ, the transition state geometries are quite similar, and by analyzing the energetics of the involved distortions accompanying the structural changes, a significant contribution to the basis for the rate differences was identified. Using this knowledge, a simplified computational method for evaluating ligand structural influences on cyclic ester ROP rates is proposed that may have utility for future catalyst design. PMID- 26900490 TI - Adherence of Academic Radiologists in a Non-English Speaking Imaging Center to the BI-RADS Standards of Reporting Breast MRI. AB - OBJECTIVES: To assess the adherence of academic radiologists in a university center to BI-RADS lexicon (BLA) and to evaluate the structural completeness of breast MRI reports. MATERIALS AND METHODS: Breast MRI reports made during 2012 in a single academic center by six readers were scored for formal completeness (FS) including recording the MRI protocol, making relevant clinical correlation, and describing background enhancement; BLA including mass rather than lesion, describing lesion outline, enhancement characteristics, and dynamic curve; and also expressing the final conclusion using BLA, resulting in a maximal total score of 8. FS and BLA were correlated with reader characteristics including breast imaging background, years of academic experience, and number of breast MRIs reported yearly. Tests used for statistical analysis were the Mann-Whitney U test and analysis of variance (ANOVA). RESULTS: Overall BLA was 38.9%. This percentage was 60.1% and 3.7% in radiologists with and without breast imaging background, respectively (P = 0.000). Mean FS among all readers was 3.81 +/- 1.75. This score was 2.54 +/- 1.1 for readers without breast imaging background and 4.6 +/- 1.6 for the readers regularly involved in breast imaging (P = 0.000). CONCLUSIONS: Higher degree of BLA and higher mean FS were associated with radiologists regularly involved in breast imaging. No association was found with years of academic experience or number of breast MRIs interpreted yearly. PMID- 26900489 TI - Specimen Referral Network to Rapidly Scale-Up CD4 Testing: The Hub and Spoke Model for Haiti. AB - OBJECTIVES: Regular and quality CD4 testing is essential to monitor disease progression in people living with HIV. In Haiti, most laboratories have limited infrastructure and financial resources and have relied on manual laboratory techniques. We report the successful implementation of a national specimen referral network to rapidly increase patient coverage with quality CD4 testing while at the same time building infrastructure for referral of additional sample types over time. METHOD: Following a thorough baseline analysis of facilities, expected workload, patient volumes, cost of technology and infrastructure constraints at health institutions providing care to HIV patients, the Haitian National Public Health Laboratory designed and implemented a national specimen referral network. The specimen referral network was scaled up in a step-wise manner from July 2011 to July 2014. RESULTS: Fourteen hubs serving a total of 67 healthcare facilities have been launched; in addition, 10 healthcare facilities operate FACSCount machines, 21 laboratories operate PIMA machines, and 11 healthcare facilities are still using manual CD4 tests. The number of health institutions able to access automated CD4 testing has increased from 27 to 113 (315%). Testing volume increased 76% on average. The number of patients enrolled on ART at the first healthcare facilities to join the network increased 182% within 6 months following linkage to the network. Performance on external quality assessment was acceptable at all 14 hubs. CONCLUSION: A specimen referral network has enabled rapid uptake of quality CD4 testing, and served as a backbone to allow for other future tests to be scaled-up in a similar way. PMID- 26900491 TI - Cardiac Tamponade as Initial Presentation of Hodgkin Lymphoma. AB - Cardiac involvement in malignant lymphoma is one of the least investigated subjects. Pericardial effusion is rarely symptomatic in patients of Hodgkin lymphoma (HL). Few case reports are available in the literature. There are case reports of diagnosed HL patients presenting with pericardial effusion. HL patients who present with recurrent episodes of pericardial effusion have also been reported. Pericardial effusion has also been reported in cases of non HL. However, pericardial effusion leading to cardiac tamponade as an initial presentation of HL is extremely rare. Very few such cases are there in the literature. Here, we present a case of a 26-year-old male patient who presented with cardiac tamponade and in due course was found to be a case of classical type of HL. This case is interesting because of its presentation. PMID- 26900492 TI - Magnetic Resonance Imaging Features of a Juxtaglomerular Cell Tumor. AB - OBJECTIVE: To retrospectively determine whether magnetic resonance imaging (MRI) findings can help differentiate a juxtaglomerular cell tumor (JCT) from clear cell renal cell carcinoma (ccRCC). MATERIALS AND METHODS: Eight patients with JCTs and 24 patients with pathologically proven ccRCC were included for image analysis. All patients underwent unenhanced MRI and dynamic contrast-enhanced MRI. Fat-suppressed T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), in- and opposed-phase imaging, and fat-suppressed preliver acquisitions with volume acceleration sequences were performed before enhancement. After the administration of contrast, dynamic imaging was performed in the corticomedullary, nephrographic, and excretory phases. Student's t-test, t'-test, Chi-square test, and nonparametric Kruskal-Wallis H-test were used to determine the significance of the difference between the two groups. The sensitivity and specificity of the MRI findings were calculated. RESULTS: In patients with a JCT, a cystic part of the lesion of <10%, isointensity or mild hyperintensity on T2WI, heterogeneous hyperintensity on DWI, less signal drop (<10%) in in- and opposed phase imaging, and a degree of enhancement <200% in the corticomedullary phase showed statistically significant differences compared with those of ccRCC (P < 0.05). After combining a lower apparent diffusion coefficient (ADC) value (heterogeneous hyperintensity) on DWI and a degree of enhancement <200% in the corticomedullary phase using a parallel test, the sensitivity and specificity were 90.9% and 91.7%, respectively. CONCLUSIONS: Isointensity or mild hyperintensity on T2WI, a lower ADC value (heterogeneous hyperintensity) on DWI, and a degree of enhancement <200% in the corticomedullary phase are the major MRI findings for JCTs, combined with relative clinical manifestations and excluding other renal masses. A main solid tumor, less signal drop (<10%) in in- and opposed-phase imaging, and a less-washout pattern of <10% in the delayed phase are secondary MRI findings for JCTs. PMID- 26900493 TI - Perirenal PEComa: Computed Tomography Findings and Differential Diagnosis. AB - The World Health Organization defines perivascular epithelioid cell tumors (PEComas) as mesenchymal tumors and tumor-like conditions composed of epithelioid cells with a perivascular distribution. These tumors may show benign or malignant histology and/or biological behavior. However, the pathological features of malignancy may not correlate with biologic aggressiveness, and the criteria for malignancy are not clearly defined. Abdominopelvic PEComas are very rare and have been reported in various locations, including kidney, liver, pancreas, gastrointestinal tract, genitourinary tract, peritoneum, and retroperitoneum. Cross-sectional imaging techniques, including computed tomography (CT) may play an important role in the accurate detection and characterization of these tumors. We present the third case of an extremely rare PEComa with perirenal location, discuss CT findings and differential diagnosis. PMID- 26900494 TI - The Role of DNA Mismatch Repair and Recombination in the Processing of DNA Alkylating Damage in Living Yeast Cells. AB - It is proposed that mismatch repair (MMR) mediates the cytotoxic effects of DNA damaging agents by exerting a futile repair pathway which leads to double strand breaks (DSBs). Previous reports indicate that the sensitivity of cells defective in homologous recombination (HR) to DNA alkylation is reduced by defects in MMR genes. We have assessed the contribution of different MMR genes to the processing of alkylation damage in vivo. We have directly visualized recombination complexes formed upon DNA damage using fluorescent protein (FP) fusions. We find that msh6 mutants are more resistant than wild type cells to MNNG, and that an msh6 mutation rescues the sensitivity of rad52 strains more efficiently than an msh3 mutation. Analysis of RAD52-GFP tagged strains indicate that MNNG increases repair foci formation, and that the inactivation of the MHS2 and MSH6 genes but not the MSH3 gene result in a reduction of the number of foci formed. In addition, in the absence of HR, NHEJ could process the MNNG-induced DSBs as indicated by the formation of NHEJ-GFP tagged foci. These data suggest that processing of the alkylation damage by MMR, mainly by MSH2-MSH6, is required for recruitment of recombination proteins to the damage site for repair. PMID- 26900495 TI - DRY NEEDLING IN SUBJECTS WITH MUSCULAR TRIGGER POINTS IN THE LOWER QUARTER: A SYSTEMATIC REVIEW. AB - BACKGROUND: Trigger points, which have been defined as highly localized, hyperirritable locations in a palpable taut band of skeletal muscle fibers, have been identified with a variety of musculoskeletal conditions. The incidence of trigger point pain is high, with studies showing them as the primary source of pain in 30-85% of patients presenting in a primary care setting or pain clinic. Dry needling has emerged as a possible intervention for trigger points, but its effectiveness has not yet fully been determined. PURPOSE: To assess and provide a summary on the current literature for the use of dry needling as an intervention for lower quarter trigger points in patients with various orthopedic conditions. STUDY DESIGN: Systematic review. METHODS: CINAHL, NCBI-PubMed, PEDro, SPORTDiscus, Cochrane Library, and APTA's PTNow were searched to identify relevant randomized controlled trials. Six studies meeting the inclusion criteria were analyzed using the PEDro scale. RESULTS: Four of the studies assessed by the PEDro scale were deemed 'high' quality and two were 'fair' quality. Each of the six included studies reported statistically significant improvements with dry needling for the reduction of pain intensity in the short-term. Only one study reported a statistically significant improvement in short-term functional outcomes; however, there was no maintenance of improved function at long-term follow-up. Furthermore, none of the studies reported statistically significant changes regarding the effect of dry needling on quality of life, depression, range of motion, or strength. CONCLUSION: A review of current literature suggests that dry needling is effective in reducing pain associated with lower quarter trigger points in the short-term. However, the findings suggest that dry needling does not have a positive effect on function, quality of life, depression, range of motion, or strength. Further high quality research with long-term follow-up investigating the effect of dry needling in comparison to and in conjunction with other interventions is needed to determine the optimal use of dry needling in treating patients with lower quarter trigger points. LEVELS OF EVIDENCE: 1. PMID- 26900496 TI - VALIDATION OF TWO CLINICAL MEASURES OF CORE STABILITY. AB - BACKGROUND: Emerging evidence suggests poor core stability is a risk factor for low back and lower extremity injuries in athletes. Recently the trunk stability test (TST) and unilateral hip bridge endurance test (UHBE) were developed to clinically assess core stability. Although these and other clinical tests of core stability exist, how well they assess core stability when compared to biomechanical measures of isolated core stability has not been thoroughly evaluated. PURPOSE/HYPOTHESIS: The purposes of this study were to 1) determine concurrent validity of two novel clinical core stability assessments (TST and UHBE), and 2) assess relationships between these assessments and the trunk endurance and Y-Balance tests. The authors' hypothesized that the TST and UHBE would be highly correlated to the lab-based biomechanical measure of isolated core stability. Also, the TST and UHBE would be moderately correlated with each other, but not with the trunk extensor endurance and Y-Balance. STUDY DESIGN: Cross-Sectional design. METHODS: Twenty healthy active individuals completed the TST (recorded number of errors), UHBE (s), trunk extensor endurance (s), Y Balance (% leg length) test (YBT), and biomechanical test of core stability. RESULTS: Correlational analyses revealed a small, non-significant association between TST and biomechanical measures (rs = 0.2 - 0.22), while a moderate, significant relationship existed between UHBE and biomechanical measures (rs = 0.49 to -0.56, p < 0.05). There was little to no relationship between TST and UHBE (r = -0.07 to - 0.21), or TST and extensor endurance (r = -0.18 to -0.24). A moderate, significant association existed between TST and two reach directions of the YBT (r = -0.41 to -0.43, p < 0.05). CONCLUSIONS: Study data support the utility of UHBE as a clinical measure of core stability. The poor relationship between the TST and biomechanical measures, combined with observation of most control faults occurring in the lower extremity (LE) suggest the TST may not be an appropriate clinical test of core stability. LEVELS OF EVIDENCE: Level 3. PMID- 26900497 TI - TEST-RETEST RELIABILITY OF TWO CLINICAL TESTS FOR THE ASSESSMENT OF HIP ABDUCTOR ENDURANCE IN HEALTHY FEMALES. AB - BACKGROUND: Substantial deficits in performance of hip abductor in patients with common lower extremity injuries are reported in literature. Therefore, assessing hip abductor endurance might be of major importance for clinicians and researchers. PURPOSES: The purpose of this study was to examine the test-retest reliability of two hip abductor endurance tests in healthy females. Learning effect, systematic difference in the rate of perceived exertion and relationship between endurance performance and some clinical characteristics of participants were also investigated. DESIGN: Observational study, with a test-retest design. METHODS: Thirty-six healthy females, aged 18-30 years, were recruited. In two identical assessment sessions, the participants performed an isometric hip abductor strength test and two different hip abductor endurance tests. RESULTS: Isometric and dynamic endurance tests demonstrated good test-retest reliability (intraclass correlation coefficients (ICC) = 0.73 and 0.78, respectively). The standard errors of measurement (SEM) and the minimal detectable changes (MDC) were, respectively, 19.8 and 54.9 seconds for isometric endurance test and 21.2 and 58.7 repetitions for dynamic endurance test. Moderate correlation between both endurance tests (r = 0.60, p = 0.0001) and weak correlation between dynamic endurance test and strength (r = 0.44, p = 0.008) were found. CONCLUSIONS: The results of the present study demonstrate good test-retest reliability of two non instrumented clinical tests of hip abductor endurance in healthy females. LEVEL OF EVIDENCE: 2b. PMID- 26900498 TI - LOWER LIMB ASYMMETRIES IN RHYTHMIC GYMNASTICS ATHLETES. AB - BACKGROUND: Different limb training demands and limb preference may determine anthropometric and muscle force inter-limb asymmetries in Rhythmic Gymnastics (RG) athletes. PURPOSE: The purpose of this study was to evaluate the influence of lateral preference of the lower extremity on anthropometric, range of motion, and isokinetic torque measurements of RG athletes. STUDY DESIGN: Cross sectional study. METHODS: Lower limb anthropometric measurements (girth, estimated anatomical cross-sectional area), hip, knee and ankle range of motion, flexor and extensor isokinetic torques (angular velocities = 60, 180, e 240 degrees .s(-1)) and bilateral asymmetry index were evaluated in 11 international level Rhythmic Gymnastics athletes (17.9 +/- 4.0 years of age; 9.1 +/- 5,1 years of experience; 26.8 +/- 6.0 weekly training hours). RESULTS: The preferred limb showed larger thigh girth and anatomical cross-sectional area, higher ankle dorsiflexor range of motion, higher hip flexor torque at 60 degrees .s(-1) and higher plantarflexor torque at 180 degrees .s(-1) compared to the non-preferred limb. CONCLUSIONS: The observed differences seem to be strictly related to lateral preference and rhythmic gymnastics training. LEVELS OF EVIDENCE: 3. PMID- 26900499 TI - SPORTSMETRICSTM TRAINING IMPROVES POWER AND LANDING IN HIGH SCHOOL ROWERS. AB - BACKGROUND: Successful rowing participation requires leg power, back strength, cardiovascular endurance, and balance. SportsMetricsTM training improves lower limb alignment, hamstring peak torque, and vertical jump height; however, this training has not been used in athletes who row and may have different outcomes based on experience level. PURPOSE/HYPOTHESES: The purpose of this study was to compare the effects of a six-week SportsMetricsTM training program on vertical jump height (VJH), Y Balance Test (YBT), and Drop Jump Screening Test (DJST) between novice and varsity high school rowers. The authors hypothesized that following SportsmetricsTM training; novice rowers would not be different from varsity rowers in VJH and YBT. All rowers will have improved normalized knee joint separation distance in DJST following training. STUDY DESIGN: Cross sectional. METHODS: 52 (31 varsity: 16.4 +/- 0.8 years, 62.0 +/- 9.0 kg, 1.7 +/- 0.1m [mean +/- SD], 21 novice: 14.5 +/- 0.7years, 58.6 +/- 5.4 kg, 1.7 +/- 0.1m [mean +/- SD]) high school rowers completed the SportsmetricsTM training and participated in the study. Varsity rowers were defined as a returner; any new rower was considered novice. Differences in age, weight, and height were examined using independent t-tests. Repeated measures ANOVA assessed pre- to post-training differences between groups in VJH, YBT composite score (CS) and reach asymmetry (ASY), and normalized knee joint separation distance (DJST). RESULTS: VJH significantly improved for all athletes from pre- to post-training (mean +/- SD: 29.0 +/- 7.0 vs. 31.9 +/- 5.1cm; p=0.001) and normalized knee separation distance significantly increased for all athletes pre to post training at the pre-landing (mean +/- SD: 58.2 +/- 12.5 vs. 68.7 +/- 7.4%; p<0.001), landing (mean +/- SD: 49.4 +/- 18.2 vs. 66.3 +/- 14.2%; p<0.001), and take off (mean +/- SD: 47.8 +/- 18.4 vs. 64.8 +/- 13.8%; p<0.001) phases of the jump; there was no effect for group. There was no difference in varsity and novice pre to post training in YBT CS (99.3 +/- 7.5 vs. 99.7 +/- 7.1%; p=0.53) or ANT ASY (mean +/- SD: 3.4 +/- 4.6 vs. 2.7 +/- 2.3; p=0.36). CONCLUSIONS: SportsMetricsTM training improved VJH regardless of experience level; which suggests that rowers may have more leg power following training. Normalized knee joint separation distance increased to greater than 60% of hip joint separation distance following training, indicating that training reduced serious knee injury risk. LEVEL OF EVIDENCE: Level 3. PMID- 26900500 TI - THE EFFECT OF STEP RATE MANIPULATION ON FOOT STRIKE PATTERN OF LONG DISTANCE RUNNERS. AB - PURPOSE/BACKGROUND: Running gait retraining to change foot strike pattern in runners from a heel strike pattern to a non heel- strike pattern has been shown to reduce impact forces and may help to reduce running related injuries. Step rate manipulation above preferred is known to help decrease step length, foot inclination angle, and vertical mass excursion, but has not yet been evaluated as a method to change foot strike pattern. The purpose of this study was to investigate the effect of step rate manipulation on foot strike pattern in shod recreational runners who run with a heel strike pattern. A secondary purpose was to describe the effect of step rate manipulation at specific percentages above preferred on foot inclination angle at initial contact. METHODS: Forty volunteer runners, who were self-reported heel strikers and had a weekly running mileage of at least 10 miles, were recruited. Runners were confirmed to be heel strikers during the warm up period on the treadmill. The subject's step rate was determined at their preferred running pace. A metronome was used to increase step rate above the preferred step rate by 5%, 10% and 15%. 2D video motion analysis was utilized to determine foot strike pattern and to measure foot inclination angle at initial contact for each step rate condition. RESULTS: There was a statistically significant change in foot strike pattern from a heel strike pattern to a mid-foot or forefoot strike pattern at both 10% and 15% step rates above preferred. Seven of the 40 subjects (17.5%) changed from a heel- strike pattern to a non- heel strike pattern at +10% and 12 of the 40 subjects (30%) changed to a non-heel strike pattern at +15%. Mean foot inclination angle at initial contact showed a statistically significant change (reduction) as step rate increased. CONCLUSION: Step rate manipulation of 10% or greater may be enough to change foot strike pattern from a heel strike to a mid-foot or forefoot strike pattern in a small percentage of recreational runners who run in traditional running shoes. If changing the foot strike pattern is the main goal, other gait re-training methods may be needed to make a change from a heel strike to a non-heel strike pattern. Step rate manipulation shows a progressive reduction of foot inclination angle at 5%, 10%, and 15% above preferred step rate which reduces the severity of the heel strike at initial contact. Step rate manipulation of at least +10% above preferred may be an effective running gait retraining method for clinicians to decrease the severity of heel strike and possibly assist a runner to change to a non-heel strike pattern. LEVEL OF EVIDENCE: 3. PMID- 26900501 TI - THE USE OF A STATIC MEASURE TO PREDICT FOOT POSTURE AT MIDSUPPORT DURING RUNNING. AB - BACKGROUND: The posture of the foot has been implicated as a factor in the development of running-related injuries. A static measure of foot posture, such as the longitudinal arch angle (LAA), that can be easily performed and is predictive of the posture of the foot at midsupport while running could provide valuable information to enhance the clinician's overall evaluation of the runner. PURPOSE: The purpose of this study was to determine if the LAA, assessed in relaxed standing, could predict the posture of the foot at midsupport while running on a treadmill. STUDY DESIGN: Cross-sectional Study. METHODS: Forty experienced runners (mean age 26.6 years) voluntarily consented to participate. Inclusion criteria included running at least 18 miles per week, previous experience running on a treadmill, no history of lower extremity congenital or traumatic deformity, or acute injury three months prior to the start of the study. Each runner had markers placed on the medial malleolus, navicular tuberosity, and medial aspect 1(st) metatarsal head of both feet. A high speed camera (240 Hz) was used to film both feet of each runner in standing and while running on a treadmill at their preferred speed. The LAA in standing and at mid support while running was determined by angle formed by two lines drawn between the three markers with the navicular tuberosity serving as the apex. The LAA in midsupport was determined using the mean of the middle five running trials. RESULTS: The levels of intra-rater and inter-rater reliability for the dynamic LAA were excellent. The results of the t-tests indicated that mean values between the left and right foot were not significantly different for the standing or running LAA. The results of the t-tests between male and female runners were also not significantly different for standing or running LAA. The Pearson correlation between standing and running LAA for all 80 feet was r = 0.95 (r(2) = 0.90). CONCLUSIONS: The standing LAA was found to be highly predictive of the running LAA at midsupport while running. Approximately 90% of the variance associated with foot posture at midsupport in running could be explained by the standing LAA. LEVEL OF EVIDENCE: 4, Controlled laboratory study. PMID- 26900502 TI - RELIABILITY, COMPARABILITY, AND VALIDITY OF FOOT INVERSION AND EVERSION STRENGTH MEASUREMENTS USING A HAND-HELD DYNAMOMETER. AB - BACKGROUND: There are conflicting results with respect to the validity and reliability of lower extremity strength measurements using a hand-held dynamometer (HHD) in the healthy population. Previous studies exploring foot inversion and eversion strength using a HHD were carried out with predominantly clinically affected participants in different positions. The question arises whether HHD measurements of isometric foot inversion and eversion strength performed with participants in different positions are valid, reliable and comparable and can be used alternatively. PURPOSE: The aims of this study were to investigate: a) the intra- and inter-tester reliability of measurements of foot inversion and eversion strength in different participant positions using a belt stabilized HHD; b) the comparability of results obtained in different positions; and c) the concurrent validity of the aforementioned measurements using an isokinetic dynamometer. METHODS: Thirty adults (12 females and 18 males; mean age 22.5 +/- 3.9 years) volunteered to participate in this study. Maximal isometric foot inversion and eversion torques (Nm) were measured with participants lying supine, sitting with knees extended and lying on their side using a belt stabilized HHD. Measurements were performed independently by two physiotherapists over two days and were repeated using an isokinetic dynamometer. Validity and intra- and inter-tester reliability were determined using the intra-class correlation coefficient (ICC). A two-way ANOVA (p < 0.05) and post-hoc tests with Bonferroni correction were used to compare data from different positions. Bland Altman plots were used to demonstrate the range of error and difference between HHD and isokinetic measurements. RESULTS: Intra-tester reliability for inversion and eversion torques was fair to excellent in all positions (ICC = 0.598-0.828). Excellent inter-tester reliability was found for eversion torques in all positions (ICC = 0.773-0.860). For inversion torques, inter-tester reliability was fair to excellent (ICC = 0.519-0.879). ICC values of 0.205 to 0.562 indicated a low to fair concurrent validity. A significant difference was observed between the torques of the supine and side-lying positions as well as sitting and side lying positions (p < 0.05). Bland-Altman plots showed that the mean of the differences for inversion and eversion torques deviates considerably from zero, indicating that measurements with the HHD in the three positions produce lower values compared to using the isokinetic dynamometer. CONCLUSIONS: Inversion and eversion strength measurements with subjects in different positions using HHD seem to be reliable, but consistently underestimated torque output when compared with measurements using isokinetic dynamometry. While the HHD outcomes measured in supine and sitting positions seem to be comparable, those measured in supine/sitting and side-lying positions differed. LEVEL OF EVIDENCE: Diagnostic study, Level 3. PMID- 26900503 TI - INTERSESSION RELIABILITY OF UPPER EXTREMITY ISOKINETIC PUSH-PULL TESTING. AB - BACKGROUND: Based on the frequency pushing and pulling patterns are used in functional activities, there is a need to establish an objective method of quantifying the muscle performance characteristics associated with these motions, particularly during the later stages of rehabilitation as criteria for discharge. While isokinetic assessment offers an approach to quantifying muscle performance, little is known about closed kinetic chain (CKC) isokinetic testing of the upper extremity (UE). PURPOSE: To determine the intersession reliability of isokinetic upper extremity measurement of pushing and pulling peak force and average power at slow (0.24 m/s), medium (0.43 m/s) and fast (0.61 m/s) velocities in healthy young adults. The secondary purpose was to compare pushing and pulling peak force (PF) and average power (AP) between the upper extremity limbs (dominant, non dominant) across the three velocities. METHODS: Twenty-four physically active men and women completed a test-retest (>96 hours) protocol in order to establish isokinetic UE CKC reliability of PF and AP during five maximal push and pull repetitions at three velocities. Both limb and speed orders were randomized between subjects. RESULTS: High test-retest relative reliability using intraclass correlation coefficients (ICC2, 1) were revealed for PF (.91-.97) and AP (.85 .95) across velocities, limbs and directions. PF typical error (% coefficient of variation) ranged from 6.1% to 11.3% while AP ranged from 9.9% to 26.7%. PF decreased significantly (p < .05) as velocity increased whereas AP increased as velocity increased. PF and AP during pushing were significantly greater than pulling at all velocities, however the push-pull differences in PF became less as velocity increased. There were no significant differences identified between the dominant and nondominant limbs. CONCLUSION: Isokinetically derived UE CKC push pull PF and AP are reliable measures. The lack of limb differences in healthy normal participants suggests that clinicians can consider bilateral comparisons when interpreting test performance. The increase in pushing PF and AP compared to pulling can be attributed to the muscles involved and the frequency that pushing patterns are used during functional activities. LEVEL OF EVIDENCE: 3. PMID- 26900504 TI - THE EFFECT OF AXIOSCAPULAR AND ROTATOR CUFF EXERCISE TRAINING SEQUENCE IN PATIENTS WITH SUBACROMIAL IMPINGEMENT SYNDROME: A RANDOMIZED CROSSOVER TRIAL. AB - BACKGROUND: While physical therapy is an effective element in the rehabilitation of rotator cuff (RC) disease, the most effective sequence of exercise training interventions has not been defined. HYPOTHESIS/PURPOSE: The purpose of this study is to determine if there is a difference in pain or function in patients who are given RC strengthening prior to or after initiating scapular stabilization exercises. STUDY DESIGN: Level I randomized crossover trial. METHODS: This was a prospective study of 26 men and 14 women with a mean age 51 who were diagnosed with subacromial impingement syndrome (SAIS). They were randomly assigned to one of two groups for a comprehensive and standardized rehabilitation program over six visits at an orthopedic outpatient clinic. One group was prescribed a 4-week program of scapular stabilization exercises while the other group began with RC strengthening exercises. The crossover design had each group add the previously excluded four exercises to their second month of rehabilitation. RESULTS: The results showed significant improvements in pain (p < 0.001), function (p < 0.001), and patient satisfaction (p < 0.001) at all follow-up times for both groups. There was not a statistically significant difference in pain or function at any follow-up period for initiating one group of exercise before the other (p > 0.05). There was a statistically significant interaction between the patient's global rating of change at the 4 week follow-up as compared to 8 weeks (p = 0.04) or 16 (p < 0.001). CONCLUSION: Patients with SAIS demonstrate improvement in pain and function with a standardized program of physical therapy regardless of group exercise sequencing. LEVEL OF EVIDENCE: 1b. PMID- 26900505 TI - COMPARISON OF SCAPULAR MUSCLE ACTIVATIONS DURING THREE OVERHEAD THROWING EXERCISES. AB - BACKGROUND: With shoulder pain and injury on the rise in overhead athletes, clinicians are often examining preventative exercises to address functional abnormalities. Because shoulder impingement is prevalent in overhead athletes, much focus is on scapular stability and the function of the stabilizing force couple of the upper and lower trapezius and serratus anterior. HYPOTHESIS/PURPOSE: The purpose of this study was to examine scapular muscle activation during a series of throws and holds (throwing without releasing) with two different ball weights (7oz and 12oz). It was hypothesized that the holds exercises would elicit greater activation of the scapular musculature than the throw, irrespective of ball weight. STUDY DESIGN: Case control laboratory study. METHODS: Twenty-two NCAA Division I, right hand dominant, softball players (19.91 + 1.04 years; 169.24 + 7.36 cm; 72.09 + 10.61 kg) volunteered to participate. Surface EMG was utilized to measure muscle activity in the upper, middle and lower trapezius and serratus anterior muscles during three different throwing activities. RESULTS: MANOVA results revealed no significant differences in muscle activity between throwing conditions, F(16,82) = 1.02, p = 0.446, Wilks' Lambda = 0.696, Cohen's d = 0.44 (7oz holds), 0.24 (12oz holds), power = 0.625. CONCLUSION/CLINICAL RELEVANCE: The results may provide some clinical insight in advocating the use of holds with different ball weights. The holds throw may be an effective step in shoulder strengthening that can more closely mimic the functional movement of throwing without the element of ball release. LEVELS OF EVIDENCE: Level 3. PMID- 26900506 TI - A COMPARISON BETWEEN CIVILIAN AND MILITARY PHYSICAL THERAPISTS' KNOWLEDGE IN MANAGING MUSCULOSKELETAL CONDITIONS: A DESCRIPTIVE STUDY. AB - BACKGROUND: Military physical therapists have been shown to have the necessary knowledge in musculoskeletal medicine in order to practice as a direct access provider. However, research about musculoskeletal knowledge in the civilian physical therapist (non-military) population is lacking. PURPOSE: The purpose of the current study was to compare the knowledge in managing musculoskeletal conditions between civilian and military physical therapists using a validated and standardized musculoskeletal competency examination. Furthermore, this study aims to investigate the potential factors that may lead to increased musculoskeletal competency. STUDY DESIGN: Cross-sectional, electronic survey. METHODS: This study involved a cross-sectional, electronic survey completed in August and September of 2014 in order to assess licensed physical therapists' knowledge in identifying and managing musculoskeletal conditions. Only physical therapists practicing in orthopedics were permitted to be involved in the study. Descriptive statistics of the participants, and logistic regressions analyzing variables correlated with passing the musculoskeletal exam were calculated using SPSS 22.0. Frequencies were produced for multiple variables. Binary logistic regressions were used to correlate the frequency variables with performing at competency level on the musculoskeletal exam. RESULTS: A total of 22,750 surveys were sent to physical therapists in Arizona, Ohio, Texas, Maine and Wyoming. Two thousand sixty-five surveys were returned for a response rate of 10.6%. Of the 2,065 surveys completed, 408 responses were included for analysis. The average score for the respondents on the exam was 65.08% and only 28.2% of all respondents met the competency cutoff score (previously established to be 73.1%). Respondents who were orthopedic certified specialists (OCS) or sports certified specialists (SCS) were 3.091 times more likely to perform at the competency level on the examination with a p-value of < 0.001 and a confidence interval >95%. CONCLUSION: The current study utilized the results from a previous study for a comparison between the civilian and military physical therapist populations. The results indicate that civilian physical therapists in the current study (65.08%) scored lower than their military counterparts in the previous study (75.9%) on the musculoskeletal exam. Potential reasons for this include less autonomous practice responsibilities and a disparity in educational experiences. Board certifications may enhance civilian physical therapists ability to practice with greater autonomy as primary care clinicians when managing musculoskeletal conditions. LEVEL OF EVIDENCE: Level 4. PMID- 26900507 TI - PREVALENCE OF MUSCULOSKELETAL PAIN IN MARATHON RUNNERS WHO COMPETE AT THE ELITE LEVEL. AB - BACKGROUND: Musculoskeletal pain can be an important sign of overuse injury in elite athletes. However, its prevalence and whether it is associated with aspects of training in marathon runners who compete at the elite level is still not clear. PURPOSE: The purpose of this research was to assess the prevalence, location and intensity of running-related musculoskeletal pain over the previous 12 months in marathon runners who compete at the elite level and to verify whether certain training characteristics are associated with musculoskeletal pain. DESIGN: Cross sectional study. METHODS: One hundred and ninety-nine elite marathon runners were verbally interviewed regarding their personal demographics, training routines, and the presence, location and intensity of musculoskeletal pain. RESULTS: The prevalence of any running-related musculoskeletal pain in elite distance runners was 75%, and the most frequently reported location was the lower leg (19.1%). The presence of pain was independent of age, experience, and volume of training. CONCLUSIONS: Running-related musculoskeletal pain is highly prevalent in marathon runners who compete at the elite level. CLINICAL RELEVANCE: Studies about prevalence and location of musculoskeletal pain and factors-related in this population are important to contribute to the development of educational and preventive strategies. EVIDENCE LEVEL: 2. PMID- 26900508 TI - INJURIES IN DISC GOLF - A DESCRIPTIVE CROSS-SECTIONAL STUDY. AB - BACKGROUND: Disc golf is rapidly increasing in popularity and more than two million people are estimated to regularly participate in disc golf activities. Despite this popularity, the epidemiology of injuries in disc golf remains under reported. PURPOSE: The purpose of the present study was to investigate the prevalence and anatomic distribution of injuries acquired through disc-golf participation in Danish disc golf players. METHODS: The study was a cross sectional study conducted on Danish disc-golf players. In May 2015, invitations to complete a web-based questionnaire were spread online via social media, and around disc-golf courses in Denmark. The questionnaire included questions regarding disc-golf participation and the characteristics of injuries acquired through disc golf participation. The data was analyzed descriptively. RESULTS: An injury prevalence of 13.3% (95% CI: 6.7% to 19.9%) was reported amongst the 105 disc-golf players who completed the questionnaire. The anatomical locations most commonly affected by injury were the shoulder (31%) and the elbow (20%). Injuries affecting the players at the time of completion of the questionnaire had a median duration of 240 days (IQR 1410 days), and the majority (93%) had a gradual onset. CONCLUSIONS: A 13.3% point prevalence of injury was reported. Most injuries occurred in the shoulder and elbow regions, and were gradual in onset. Injuries affecting the players at the time of data collection had median symptomatic duration of 240 days. LEVELS OF EVIDENCE: 3b. PMID- 26900509 TI - CLINICAL APPLICATIONS OF CRYOTHERAPY AMONG SPORTS PHYSICAL THERAPISTS. AB - BACKGROUND: Therapeutic modalities (TM) are used by sports physical therapists (SPT) but how they are used is unknown. PURPOSE: To identify the current clinical use patterns for cryotherapy among SPT. STUDY DESIGN: Cross-sectional survey. METHODS: All members (7283) of the Sports Physical Therapy Section of the APTA were recruited. A scenario-based survey using pre-participation management of an acute or sub-acute ankle sprain was developed. A Select Survey link was distributed via email to participants. Respondents selected a treatment approach based upon options provided. Follow-up questions were asked. The survey was available for two weeks with a follow-up email sent after one week. Question answers were the main outcome measures. RESULTS: Reliability: Cronbach's alpha=>0.9. The SPT response rate = 6.9% (503); responses came from 48 states. Survey results indicated great variability in respondents' approaches to the treatment of an acute and sub-acute ankle sprain. CONCLUSIONS AND CLINICAL RELEVANCE: SPT applied cryotherapy with great variability and not always in accordance to the limited research on the TM. Continuing education, application of current research, and additional outcomes based research needs to remain a focus for clinicians. LEVEL OF EVIDENCE: 3. PMID- 26900510 TI - Hexanoyl-Chitosan-PEG Copolymer Coated Iron Oxide Nanoparticles for Hydrophobic Drug Delivery. AB - Nanoparticle (NP) formulations may be used to improve in vivo efficacy of hydrophobic drugs by circumventing solubility issues and providing targeted delivery. In this study, we developed a hexanoyl-chitosan-PEG (CP6C) copolymer coated, paclitaxel (PTX)-loaded, and chlorotoxin (CTX) conjugated iron oxide NP (CTX-PTX-NP) for targeted delivery of PTX to human glioblastoma (GBM) cells. We modified chitosan with polyethylene glycol (PEG) and hexanoyl groups to obtain the amphiphilic CP6C. The resultant copolymer was then coated onto oleic acid stabilized iron oxide NPs (OA-IONP) via hydrophobic interactions. PTX, a model hydrophobic drug, was loaded into the hydrophobic region of IONPs. CTX-PTX-NP showed high drug loading efficiency (>30%), slow drug release in PBS and the CTX conjugated NP was shown to successfully target GBM cells. Importantly, the NPs showed great therapeutic efficacy when evaluated in GBM cell line U-118 MG. Our results indicate that this nanoparticle platform could be used for loading and targeted delivery of hydrophobic drugs. PMID- 26900511 TI - ATRP Synthesis of Sunflower Polymers using Cyclic Multimacroinitiators. AB - Polymers with advanced architectures can now be readily and reproducibly synthesized using controlled living polymerization. These materials are attractive as potential drug carriers due to their tunable size, versatile methods of drug incorporation and release, and ease of functionalization with targeting ligands. In this work, we report the design and development of macrocyclic brush, or "sunflower," polymers, synthesized by controlled radical polymerization of hydrophilic "petals" from a cyclic multimacroinitiator "core." These nanostructures can be synthesized with low polydispersity and controlled sizes depending on polymerization time. We further demonstrate that folate functionalized sunflower polymers facilitate receptor-mediated uptake into cancer cells. These materials therefore show potential as drug carriers for anti-cancer therapies. PMID- 26900512 TI - Researcher-library collaborations: Data repositories as a service for researchers. AB - INTRODUCTION: New interest has arisen in organizing, preserving, and sharing the raw materials-the data and metadata-that undergird the published products of research. Library and information scientists have valuable expertise to bring to bear in the effort to create larger, more diverse, and more widely used data repositories. However, for libraries to be maximally successful in providing the research data management and preservation services required of a successful data repository, librarians must work closely with researchers and learn about their data management workflows. DESCRIPTION OF SERVICES: Databrary is a data repository that is closely linked to the needs of a specific scholarly community researchers who use video as a main source of data to study child development and learning. The project's success to date is a result of its focus on community outreach and providing services for scholarly communication, engaging institutional partners, offering services for data curation with the guidance of closely involved information professionals, and the creation of a strong technical infrastructure. NEXT STEPS: Databrary plans to improve its curation tools that allow researchers to deposit their own data, enhance the user-facing feature set, increase integration with library systems, and implement strategies for long-term sustainability. PMID- 26900514 TI - Double-Focusing Thermal Triple-Axis Spectrometer at the NCNR. AB - The new thermal triple-axis spectrometer at the NIST Center for Neutron Research (NCNR) is located at the BT-7 beam port. The 165 mm diameter reactor beam is equipped with a selection of Soller collimators, beam-limiters, and a pyrolytic graphite (PG) filter to tailor the beam for the dual 20*20 cm(2) double-focusing monochromator system that provides monochromatic fluxes exceeding 10(8) n/cm(2)/s onto the sample. The two monochromators installed are PG(002) and Cu(220), which provide incident energies from 5 meV to above 500 meV. The computer controlled analyzer system offers six standard modes of operation, including a diffraction detector, a position-sensitive detector (PSD) in diffraction mode, horizontal energy focusing analyzer with detector, a Q-E mode employing a flat analyzer and PSD, a constant-E mode with the analyzer crystal system and PSD, and a conventional mode with a selection of Soller collimators and detector. Additional configurations for specific measurement needs are also available. This paper discusses the capabilities and performance for this new state-of-the-art neutron spectrometer. PMID- 26900513 TI - The Interaction of Radio-Frequency Fields With Dielectric Materials at Macroscopic to Mesoscopic Scales. AB - The goal of this paper is to overview radio-frequency (RF) electromagnetic interactions with solid and liquid materials from the macroscale to the nanoscale. The overview is geared toward the general researcher. Because this area of research is vast, this paper concentrates on currently active research areas in the megahertz (MHz) through gigahertz (GHz) frequencies, and concentrates on dielectric response. The paper studies interaction mechanisms both from phenomenological and fundamental viewpoints. Relaxation, resonance, interface phenomena, plasmons, the concepts of permittivity and permeability, and relaxation times are summarized. Topics of current research interest, such as negative-index behavior, noise, plasmonic behavior, RF heating, nanoscale materials, wave cloaking, polaritonic surface waves, biomaterials, and other topics are overviewed. Relaxation, resonance, and related relaxation times are overviewed. The wavelength and material length scales required to define permittivity in materials is discussed. PMID- 26900515 TI - NIST Ionization Chamber "A" Sample-Height Corrections. AB - For over 30 years scientists in the NIST radioactivity group have been using their pressurized ionization chamber "A" (PIC "A") to make measurements of radioactivity and radioactive half-lives. We now have evidence that some of those reported measurements were incorrect due to slippage of the source positioning ring over time. The temporal change in the holder caused an error in the source height within the chamber, which was thought to be invariant. This unaccounted for height change caused a change in the detector response and thus a relative error in measured activity on the order of 10(-5) to 10(-3) per year, depending on the radionuclide. The drifting detector response affected calibration factors and half-life determinations. After discovering the problem, we carried out historic research and new sensitivity tests. As a result, we have created a quantitative model of the effect and have used that model to estimate corrections to some of the past measurement results from PIC "A". In this paper we report the details and results of that model. Meanwhile, we have fixed the positioning ring and are recalibrating the detector using primary measurement methods and enhanced quality control measures. PMID- 26900516 TI - Standardization of Broadband UV Measurements for 365 nm LED Sources. AB - Broadband UV measurements are evaluated when UV-A irradiance meters measure optical radiation from 365 nm UV sources. The CIE standardized rectangular-shape UV-A function can be realized only with large spectral mismatch errors. The spectral power-distribution of the 365 nm excitation source is not standardized. Accordingly, the readings made with different types of UV meters, even if they measure the same UV source, can be very different. Available UV detectors and UV meters were measured and evaluated for spectral responsivity. The spectral product of the source-distribution and the meter's spectral-responsivity were calculated for different combinations to estimate broad-band signal-measurement errors. Standardization of both the UV source-distribution and the meter spectral responsivity is recommended here to perform uniform broad-band measurements with low uncertainty. It is shown what spectral responsivity function(s) is needed for new and existing UV irradiance meters to perform low-uncertainty broadband 365 nm measurements. PMID- 26900517 TI - The Effect of Non-equispaced Sampling Instants, Sub-period Record Epochs, and Timebase Gain on the Information Content of Discretized Replicas of Periodic Signals. AB - The effect of non-equispaced sampling instants and timebase gain on the information content of the discretized replica of a periodic signal is examined. The effect of the duration of record epochs that are not equal to an integer number of signal periods on the information content of the discretized replica is also explored. A general model describing sampled and windowed data is provided and compared to related models developed by other researchers. PMID- 26900518 TI - Fractional Diffusion, Low Exponent Levy Stable Laws, and 'Slow Motion' Denoising of Helium Ion Microscope Nanoscale Imagery. AB - Helium ion microscopes (HIM) are capable of acquiring images with better than 1 nm resolution, and HIM images are particularly rich in morphological surface details. However, such images are generally quite noisy. A major challenge is to denoise these images while preserving delicate surface information. This paper presents a powerful slow motion denoising technique, based on solving linear fractional diffusion equations forward in time. The method is easily implemented computationally, using fast Fourier transform (FFT) algorithms. When applied to actual HIM images, the method is found to reproduce the essential surface morphology of the sample with high fidelity. In contrast, such highly sophisticated methodologies as Curvelet Transform denoising, and Total Variation denoising using split Bregman iterations, are found to eliminate vital fine scale information, along with the noise. Image Lipschitz exponents are a useful image metrology tool for quantifying the fine structure content in an image. In this paper, this tool is applied to rank order the above three distinct denoising approaches, in terms of their texture preserving properties. In several denoising experiments on actual HIM images, it was found that fractional diffusion smoothing performed noticeably better than split Bregman TV, which in turn, performed slightly better than Curvelet denoising. PMID- 26900519 TI - A Comparison of Harwell & FWT Alanine Temperature Coefficients from 25 degrees C to 80 degrees C. AB - The dosimeters used to monitor industrial irradiation processing commonly experience significant temperature rises that must be considered in the dose analysis stage. The irradiation-temperature coefficient for a dosimetry system is derived from the dosimeter's radiation response to the absorbed dose and the irradiation temperature. This temperature coefficient is typically expressed in percent change per degree. The temperature rise in dosimeters irradiated with high-intensity ionizing radiation sources can be appreciable. This is especially true for electron-beam processing in which dosimeter temperatures can approach 80 degrees C. A recent National Institute of Standards and Technology (NIST) study revealed modest (0.5 % to 1.0 %) deviations from the predicted value at temperatures above 70 degrees C for absorbed doses of 1 kGy and 20 kGy. However, these data were inconsistent with a concurrent manuscript published by National Physical Laboratory (NPL) researchers that found a significant dose-dependent non linear alanine response but used dosimeters from a different manufacturer and a different experimental design. The current work was undertaken to reconcile the two studies. Alanine dosimeters from each manufacturer used by NIST and NPL were co-irradiated over a wide range of absorbed dose and irradiation temperature. It was found that though there was a slight variation in the temperature coefficient between the two alanine dosimeter sources both systems were linear with irradiation temperature up to 70 degrees C and the NPL observations of non linearity were not reproduced. These data confirmed that there is no fundamental difference in the two commercial alanine dosimeter sources and that temperature corrections could be made on industrial irradiations at the extremes of irradiation temperature and absorbed dose. PMID- 26900520 TI - Measurements for the Development of a Simulated Naturally Occurring Radioactive Material. AB - Nineteen different commercially available samples containing naturally occurring radioactive materials (NORM) (i.e., natural uranium, thorium, radium and potassium) were investigated, including zircon sand, cat litter, roofing tiles, ice melt and fertilizer among others. A large variation in isotopic composition was observed across the measured samples. As a result of this observation, a need was identified to develop and implement the use of a simulated NORM sample to serve as a reference standard sample containing naturally occurring radioactive elements. The purpose of the simulated NORM sample would be to simulate typical samples containing NORM to be used for testing radiation detection instruments against ANSI/IEEE and IEC document standards requirements. The design and construction of the proposed new simulated NORM sample and the subsequent energy spectra characterization measurements are presented as part of this work. PMID- 26900521 TI - Computational Seebeck Coefficient Measurement Simulations. AB - We have employed finite element analysis to develop computational Seebeck coefficient metrology simulations. This approach enables a unique exploration of multiple probe arrangements and measurement techniques within the same temporal domain. To demonstrate the usefulness of this approach, we have performed these Seebeck coefficient measurement simulations to quantitatively explore perturbations to voltage and temperature correspondence, by comparing simultaneous and staggered data acquisition techniques under the quasi-steady state condition. The results indicate significant distortions to the Seebeck coefficient and a strong dependence on the time delay, the acquisition sequence, and the probe arrangement. PMID- 26900522 TI - Instrument Control (iC) - An Open-Source Software to Automate Test Equipment. AB - It has become common practice to automate data acquisition from programmable instrumentation, and a range of different software solutions fulfill this task. Many routine measurements require sequential processing of certain tasks, for instance to adjust the temperature of a sample stage, take a measurement, and repeat that cycle for other temperatures. This paper introduces an open-source Java program that processes a series of text-based commands that define the measurement sequence. These commands are in an intuitive format which provides great flexibility and allows quick and easy adaptation to various measurement needs. For each of these commands, the iC-framework calls a corresponding Java method that addresses the specified instrument to perform the desired task. The functionality of iC can be extended with minimal programming effort in Java or Python, and new measurement equipment can be addressed by defining new commands in a text file without any programming. PMID- 26900523 TI - Lunar Spectral Irradiance and Radiance (LUSI): New Instrumentation to Characterize the Moon as a Space-Based Radiometric Standard. AB - The need to understand and monitor climate change has led to proposed radiometric accuracy requirements for space-based remote sensing instruments that are very stringent and currently outside the capabilities of many Earth orbiting instruments. A major problem is quantifying changes in sensor performance that occur from launch and during the mission. To address this problem on-orbit calibrators and monitors have been developed, but they too can suffer changes from launch and the harsh space environment. One solution is to use the Moon as a calibration reference source. Already the Moon has been used to remove post launch drift and to cross-calibrate different instruments, but further work is needed to develop a new model with low absolute uncertainties capable of climate quality absolute calibration of Earth observing instruments on orbit. To this end, we are proposing an Earth-based instrument suite to measure the absolute lunar spectral irradiance to an uncertainty(1) of 0.5 % (k=1) over the spectral range from 320 nm to 2500 nm with a spectral resolution of approximately 0.3 %. Absolute measurements of lunar radiance will also be acquired to facilitate calibration of high spatial resolution sensors. The instruments will be deployed at high elevation astronomical observatories and flown on high-altitude balloons in order to mitigate the effects of the Earth's atmosphere on the lunar observations. Periodic calibrations using instrumentation and techniques available from NIST will ensure traceability to the International System of Units (SI) and low absolute radiometric uncertainties. PMID- 26900524 TI - Measurement of Scattering Cross Section with a Spectrophotometer with an Integrating Sphere Detector. AB - A commercial spectrometer with an integrating sphere (IS) detector was used to measure the scattering cross section of microspheres. Analysis of the measurement process showed that two measurements of the absorbance, one with the cuvette placed in the normal spectrometer position, and the second with the cuvette placed inside the IS, provided enough information to separate the contributions from scattering and molecular absorption. Measurements were carried out with microspheres with different diameters. The data was fitted with a model consisting of the difference of two terms. The first term was the Lorenz-Mie (L M) cross section which modeled the total absorbance due to scattering. The second term was the integral of the L-M differential cross section over the detector acceptance angle. The second term estimated the amount of forward scattered light that entered the detector. A wavelength dependent index of refraction was used in the model. The agreement between the model and the data was good between 300 nm and 800 nm. The fits provided values for the microsphere diameter, the concentration, and the wavelength dependent index of refraction. For wavelengths less than 300 nm, the scattering cross section had significant spectral structure which was inversely related to the molecular absorption. This work addresses the measurement and interpretation of the scattering cross section for wavelengths between 300 nm and 800 nm. PMID- 26900525 TI - A Model for Geometry-Dependent Errors in Length Artifacts. AB - We present a detailed model of dimensional changes in long length artifacts, such as step gauges and ball bars, due to bending under gravity. The comprehensive model is based on evaluation of the gauge points relative to the neutral bending surface. It yields the errors observed when the gauge points are located off the neutral bending surface of a bar or rod but also reveals the significant error associated with out-of-straightness of a bar or rod even if the gauge points are located in the neutral bending surface. For example, one experimental result shows a length change of greater than 1.5 um on a 1 m ball bar with an out-of straightness of 0.4 mm. This and other results are in agreement with the model presented in this paper. PMID- 26900526 TI - Sealed Gravitational Capillary Viscometry of Dimethyl Ether and Two Next Generation Alternative Refrigerants. AB - The viscosities of dimethyl ether (DME, C2H6O) and of the fluorinated propene isomers 2,3,3,3-tetrafluoroprop-1-ene (R1234yf, C3H2F4) and trans-1,3,3,3 tetrafluoropropene (R1234ze(E)) were measured in a combined temperature range from 242 K to 350 K at saturated liquid conditions. The instrument was a sealed gravitational capillary viscometer developed at NIST for volatile liquids. Calibration and adjustment of the instrument constant were conducted with n pentane. The repeatability of the measurements was found to be approximately 1.5 %, leading to a temperature-dependent estimated combined standard uncertainty of the experimental data between 5.7 % at 242 K for dimethyl ether and 2.6 % at 340 K for R1234yf. The measurements were supplemented by ab initio calculations of the molecular size, shape, and charge distributions of the measured compounds. The viscosity results for dimethyl ether were compared with literature data. One other data set measured with a sealed capillary viscometer and exceeding the present results by up to 7 % could be reconciled by applying the vapor buoyancy correction. Then, all data agreed within the estimated uncertainty of the present results. Viscosities for the fluorinated propene isomers deviate up to 4 % from values predicted with the NIST extended corresponding-states model. The viscosities of the two isomers do not scale with their dipole moments. While the measured viscosity of R1234ze(E) with the lower dipole moment is close to that of R134a, the refrigerant to be replaced, that of R1234yf with the higher dipole moment is up to 25 % lower. The viscosity of dimethyl ether is compared with those of water and methanol. PMID- 26900527 TI - Variances of Cylinder Parameters Fitted to Range Data. AB - Industrial pipelines are frequently scanned with 3D imaging systems (e.g., LADAR) and cylinders are fitted to the collected data. Then, the fitted as-built model is compared with the as-designed model. Meaningful comparison between the two models requires estimates of uncertainties of fitted model parameters. In this paper, the formulas for variances of cylinder parameters fitted with Nonlinear Least Squares to a point cloud acquired from one scanning position are derived. Two different error functions used in minimization are discussed: the orthogonal and the directional function. Derived formulas explain how some uncertainty components are propagated from measured ranges to fitted cylinder parameters. PMID- 26900528 TI - Evolution of Microwave Spectroscopy at the National Bureau of Standards (NBS) and the National Institute of Standards and Technology (NIST). AB - This paper describes the beginning and evolution of microwave rotational spectroscopic research starting in 1954 at the National Bureau of Standards (NBS), located at that time in Washington, DC, through the present at NIST in Gaithersburg, MD. David Lide was hired in 1954 to start this research employing Stark modulated waveguide septum cells. When Donald R. Johnson joined the lab in 1968, he developed parallel plate cells coupled with rf and DC discharge methods to study free radicals and transient species. In the mid 1980s Lovas and Suenram constructed a pulsed molecular beam Fourier Transform microwave (FTMW) spectrometer to study hydrogen bonded and van der Waals dimers and trimers. This article describes the types of molecules studied and the type molecular properties derived from these measurements as well as some of the instruments developed for these studies. The two major areas of application described are atmospheric chemistry and molecular radio astronomy. PMID- 26900529 TI - Reduction Formulae for Products of Theta Functions. AB - In four cases it is already known that the product of two distinct Jacobian theta functions having the same variable z and the same nome q is a multiple of a single Jacobian theta function, with the multiple independent of z. The main purpose of the present note is to show that this property also applies in the remaining two cases. PMID- 26900530 TI - Evaluation of the Current Status of the Combinatorial Approach for the Study of Phase Diagrams. AB - This paper provides an evaluation of the effectiveness of using the high throughput combinatorial approach for preparing phase diagrams of thin film and bulk materials. Our evaluation is based primarily on examples of combinatorial phase diagrams that have been reported in the literature as well as based on our own laboratory experiments. Various factors that affect the construction of these phase diagrams are examined. Instrumentation and analytical approaches needed to improve data acquisition and data analysis are summarized. PMID- 26900531 TI - Optical-Fiber Power Meter Comparison between NIST and KRISS. AB - We describe the results of a comparison of reference standards between the National Institute of Standards and Technology (NIST-USA) and Korea Research Institute of Standards and Science (KRISS-R.O. Korea) for optical fiber-based power measurements at wavelengths of 1302 nm and 1546 nm. We compare the laboratories' reference standards by means of a temperature-controlled optical trap detector. Measurement results showed the largest difference of less than 2.5 parts in 10(3), which is within the combined standard (k=1) uncertainty for the two laboratories' reference standards. PMID- 26900532 TI - Self-powered p-NiO/n-ZnO heterojunction ultraviolet photodetectors fabricated on plastic substrates. AB - A self-powered ultraviolet (UV) photodetector (PD) based on p-NiO and n-ZnO was fabricated using low-temperature sputtering technique on indium doped tin oxide (ITO) coated plastic polyethylene terephthalate (PET) substrates. The p-n heterojunction showed very fast temporal photoresponse with excellent quantum efficiency of over 63% under UV illumination at an applied reverse bias of 1.2 V. The engineered ultrathin Ti/Au top metal contacts and UV transparent PET/ITO substrates allowed the PDs to be illuminated through either front or back side. Morphology, structural, chemical and optical properties of sputtered NiO and ZnO films were also investigated. PMID- 26900533 TI - The Need and Initial Practice of Parallel Imaging and Compressed Sensing in Hyperpolarized 13C MRI in vivo. PMID- 26900536 TI - Competencies in Training at the Graduate Student Level: Example of a Pediatric Psychology Seminar Course. AB - The recently developed competencies in pediatric psychology from the Society of Pediatric Psychology (SPP) Task Force on Competencies and Best Training Practices in Pediatric Psychology provide a benchmark to evaluate training program practices and student progress toward training in level-specific competency goals. Graduate-level training presents a unique challenge for addressing the breadth of competencies required in pediatric psychology while maintaining development of broader clinical psychology training goals. We describe a recurring graduate-level pediatric psychology seminar course that addresses training in a number of the competency cluster areas. The structure of the seminar, examples of classroom topics that correspond with competency cluster areas as well as benchmarks used to evaluate each student's development in the competency area are provided. Specific challenges in developing and maintaining the seminar in this format are identified, and possible solutions are offered. This training format could serve as a model for established pediatric psychology programs to expand their didactic training goals or for programs without formal pediatric psychology training to address competencies outside of clinical placements. PMID- 26900535 TI - Compartmental and Data-Based Modeling of Cerebral Hemodynamics: Linear Analysis. AB - Compartmental and data-based modeling of cerebral hemodynamics are alternative approaches that utilize distinct model forms and have been employed in the quantitative study of cerebral hemodynamics. This paper examines the relation between a compartmental equivalent-circuit and a data-based input-output model of dynamic cerebral autoregulation (DCA) and CO2-vasomotor reactivity (DVR). The compartmental model is constructed as an equivalent-circuit utilizing putative first principles and previously proposed hypothesis-based models. The linear input-output dynamics of this compartmental model are compared with data-based estimates of the DCA-DVR process. This comparative study indicates that there are some qualitative similarities between the two-input compartmental model and experimental results. PMID- 26900534 TI - Obstacles and future of gene therapy for hemophilia. AB - INTRODUCTION: The recent success of early-phase clinical trials for adeno associated viral (AAV) liver-directed gene therapy for hemophilia B (HB) demonstrates the potential for gene therapy, in the future, to succeed protein based prophylaxis therapy for HB. Significant obstacles, however, need to be overcome prior to widespread adoption. The largest obstacles include immune responses to the AAV capsid including preexisting neutralizing antibodies (NAbs) and a delayed cellular immune response. Emerging evidence suggests that the latter is vector-dose dependent. Furthermore, the development and eradication of inhibitors remains a significant safety concern. Similarly, biological differences between Factor VIII and Factor IX (FIX) impose challenges to direct adoption of the successes for HB to hemophilia A (HA). AREAS COVERED: The advantages and limitations of the current strategies addressing these obstacles for gene therapy for HB and HA are discussed, as well as vector manufacturing issues relevant to widespread adoption. Alternative strategies including both ex vivo and in-vivo lentiviral-based methods are discussed, though we focus on AAV based approaches because of their recent clinical success and potential. EXPERT OPINION: Our opinion is that these obstacles can be overcome with current approaches, and AAV-based gene therapy for HB will likely translate into future clinical care. Innovative approaches are, however, likely needed to solve the current problems obstructing HA gene therapy. PMID- 26900537 TI - Measuring and modeling the lifetime of nitrous oxide including its variability. AB - Nitrous oxide lifetime is computed empirically from MLS satellite dataEmpirical N2O lifetimes compared with models including interannual variabilityResults improve values for present anthropogenic and preindustrial emissions. PMID- 26900538 TI - Green synthesis of silver nanoparticles: characterization and determination of antibacterial potency. AB - Silver ions (Ag+) and its compounds are highly toxic to microorganisms, exhibiting strong biocidal effects on many species of bacteria but have a low toxicity toward animal cells. In the present study, silver nanoparticles (SNPs) were biosynthesized using aqueous extract of Chlorella vulgaris as reducing agent and size of SNPs synthesized ranged between 15 and 47 nm. SNPs were characterized by UV-visible spectroscopy, scanning electron microscopy, transmission electron microscopy, X-ray diffraction and Fourier infrared spectroscopy, and analyzed for its antibacterial property against human pathogens. This approach of SNPs synthesis involving green chemistry process can be considered for the large-scale production of SNPs and in the development of biomedicines. PMID- 26900539 TI - Integrated measures for rough sets based on general binary relations. AB - Uncertainty measures are important for knowledge discovery and data mining. Rough set theory (RST) is an important tool for measuring and processing uncertain information. Although many RST-based methods for measuring system uncertainty have been investigated, the existing measures cannot adequately characterise the imprecision of a rough set. Moreover, these methods are suitable only for complete information systems, and it is difficult to generalise methods for complete information systems to incomplete information systems. To overcome these shortcomings, we present new uncertainty measures, integrated accuracy and integrated roughness, that are based on general binary relations, and we study important properties of these measures. A theoretical analysis and examples show that the proposed integrated measures are more precise than existing uncertainty measures, they are suitable for both complete and incomplete information systems, and they are logically consistent. Therefore, integrated accuracy and integrated roughness overcome the limitations of existing measures. This research not only develops the theory of uncertainty, it also expands the application domain of uncertainty measures and provides a theoretical basis for knowledge acquisition in information systems based on general binary relations. PMID- 26900541 TI - Operational method of solution of linear non-integer ordinary and partial differential equations. AB - We propose operational method with recourse to generalized forms of orthogonal polynomials for solution of a variety of differential equations of mathematical physics. Operational definitions of generalized families of orthogonal polynomials are used in this context. Integral transforms and the operational exponent together with some special functions are also employed in the solutions. The examples of solution of physical problems, related to such problems as the heat propagation in various models, evolutional processes, Black-Scholes-like equations etc. are demonstrated by the operational technique. PMID- 26900540 TI - Evaluation of wild herbivore faeces from South Africa as a potential source of hydrolytically active microorganisms. AB - This study assessed faecal matter from three indigenous South African herbivores zebra, giraffe and impala-as a potential source for hydrolytically active aerobic and facultatively anaerobic bacteria. Herbivore droppings were collected freshly in a local nature reserve in Pietermaritzburg, South Africa. Soil samples adjacent to faecal collection sites and faeces from a domestic herbivore, the Nguni cow, were included as controls. Hydrolase and dehydrogenase activity in faecal matter and soil samples were measured by the fluorescein diacetate and the triphenyltetrazolium chloride assay. Viable counts and counts for amylase, cellulase, esterase and protease producers were established using plate count agar and solid media containing cellulose, skim milk, starch and Tween 80. Zebra droppings produced the highest hydrolase and dehydrogenase activity. Faecal matter of the three indigenous herbivores generally produced higher hydrolytic activity than Nguni cow faeces and soil controls, thereby confirming that these materials are potential targets for hydrolytic enzyme mining. PMID- 26900542 TI - Assessment of genetic diversity, population structure and relationships in Indian and non-Indian genotypes of finger millet (Eleusine coracana (L.) Gaertn) using genomic SSR markers. AB - We evaluated the genetic variation and population structure in Indian and non Indian genotypes of finger millet using 87 genomic SSR primers. The 128 finger millet genotypes were collected and genomic DNA was isolated. Eighty-seven genomic SSR primers with 60-70 % GC contents were used for PCR analysis of 128 finger millet genotypes. The PCR products were separated and visualized on a 6 % polyacrylamide gel followed by silver staining. The data were used to estimate major allele frequency using Power Marker v3.0. Dendrograms were constructed based on the Jaccard's similarity coefficient. Statistical fitness and population structure analyses were performed to find the genetic diversity. The mean major allele frequency was 0.92; the means of polymorphic alleles were 2.13 per primer and 1.45 per genotype; the average polymorphism was 59.94 % per primer and average PIC value was 0.44 per primer. Indian genotypes produced an additional 0.21 allele than non-Indian genotypes. Gene diversity was in the range from 0.02 to 0.35. The average heterozygosity was 0.11, close to 100 % homozygosity. The highest inbreeding coefficient was observed with SSR marker UGEP67. The Jaccard's similarity coefficient value ranged from 0.011 to 0.836. The highest similarity value was 0.836 between genotypes DPI009-04 and GPU-45. Indian genotypes were placed in Eleusine coracana major cluster (EcMC) 1 along with 6 non-Indian genotypes. AMOVA showed that molecular variance in genotypes from various geographical regions was 4 %; among populations it was 3 % and within populations it was 93 %. PCA scatter plot analysis showed that GPU-28, GPU-45 and DPI009-04 were closely dispersed in first component axis. In structural analysis, the genotypes were divided into three subpopulations (SP1, SP2 and SP3). All the three subpopulations had an admixture of alleles and no pure line was observed. These analyses confirmed that all the genotypes were genetically diverse and had been grouped based on their geographic regions. PMID- 26900543 TI - Missing data approaches for probability regression models with missing outcomes with applications. AB - In this paper, we investigate several well known approaches for missing data and their relationships for the parametric probability regression model Pbeta (Y|X) when outcome of interest Y is subject to missingness. We explore the relationships between the mean score method, the inverse probability weighting (IPW) method and the augmented inverse probability weighted (AIPW) method with some interesting findings. The asymptotic distributions of the IPW and AIPW estimators are derived and their efficiencies are compared. Our analysis details how efficiency may be gained from the AIPW estimator over the IPW estimator through estimation of validation probability and augmentation. We show that the AIPW estimator that is based on augmentation using the full set of observed variables is more efficient than the AIPW estimator that is based on augmentation using a subset of observed variables. The developed approaches are applied to Poisson regression model with missing outcomes based on auxiliary outcomes and a validated sample for true outcomes. We show that, by stratifying based on a set of discrete variables, the proposed statistical procedure can be formulated to analyze automated records that only contain summarized information at categorical levels. The proposed methods are applied to analyze influenza vaccine efficacy for an influenza vaccine study conducted in Temple-Belton, Texas during the 2000 2001 influenza season. PMID- 26900546 TI - Lateralization of the Subthalamic Nucleus with Age in Parkinson's Disease. AB - Age-related changes in subthalamic nucleus (STN) position have not been well characterized in patients with Parkinson's disease (PD). We report a systematic retrospective analysis of age-related changes in radiographic and final deep brain stimulator (DBS) STN coordinates in PD patients. The charts of 134 PD patients (97 males, 28-84 years) representing 255 STN were reviewed. Multiple linear regression, stepwise regression, and relative importance of regressors analysis was performed to determine the significance of the relationship between STN position and age. Across all subjects, both radiographic STN localization and final DBS position within the STN showed a lateralization of the STN target with age (R2=0.1096,p=6.9*10-8 and R2=0.0433,p=8.7*10-4, respectively). Lateralization with age was observed regardless of MR field strength (1.5T and 3.0T) (R2=0.0946,p=7.6*10-6 and R2=0.2687,p=9.2*10-5, respectively). No other consistent or clinically significant age-related changes were identified. Multiple linear regression revealed that the third ventricle width and age are statistically significant predictors of radiographic STN lateralization (R2 = 0.2404, p = 1.51*10-5 and p = .00784 respectively). Step-wise regression demonstrated that age is a non-redundant predictor of STN lateralization relative to third ventricle width. Similar to healthy controls, STN position appears to shift laterally with age in PD. This highlights limitations of indirect targeting and atlas-based stereotactic surgery and argues for reliance on patient specific anatomy since factors such as age and 3rd ventricular width can contribute to patient-specific variability in STN localization. PMID- 26900547 TI - Why won't it Stick? Positive Psychology and Positive Education. AB - Following the launch of the positive psychology movement teachers and educators emerged as early adopters of this fledgling science. This approach was called positive education. It describes scientifically validated programs from positive psychology, taught in schools, that have an impact on student well-being. The growing body of evidence about the reach of positive psychology has formed a convincing case to consider well-being an operational goal for educational systems. It is argued that this goal is pivotal and should be pursued in the same way in which we develop strategies to harness academic growth, school retention rates, and student engagement. National education policies can have widespread influence at the grassroots level on school improvement, good quality of classroom teaching and learning, student performance, creating confident and creative individuals and active and informed citizens, but not necessarily on the preventative skills for lifelong well-being. In this article I take stock on the positive education movement. Three approaches to positive education are identified and eight hurdles to the field are noted as reasons why positive education won't stick in policy. Then, I reflect on two case studies: a Well being Summit and Round Table held at Wellington College and No. 10 Downing Street and Dr. Martin Seligman's role as Adelaide's Thinker in Residence as examples of grass-roots initiatives in well-being. Finally, six strategies are suggested for researchers and practitioners to grow the field. Last, I argued that until research centers focus on the development of common definitions of the key terms underpinning positive psychology, positive education and well-being the impact of the movement will be limited to a handful of institutions as models of best practice. PMID- 26900548 TI - Semitendinosus Tendon Transfer Associated With Distal Alignment for Patella Alta in a Patient With Recurrent Dislocations. AB - Patellofemoral instability is characterized by pain during normal daily activities and frequent dislocation events. In the reported case, an adolescent girl, aged 15 years, affected by left patellofemoral instability, underwent surgery with a double technique comprising tibial tubercle distalization and medial patellofemoral ligament reconstruction. In case of patella alta associated with patellofemoral instability, surgical treatment should focus on medial patellofemoral ligament repair and on recurrent instability prevention. PMID- 26900549 TI - Endoscopic Thermal Fasciotomy for Chronic Exertional Compartment Syndrome. AB - Chronic exertional compartment syndrome is an activity-induced condition that occurs when intracompartmental pressures within an osteofascial envelope increase during exercise, leading to reversible ischemic symptoms such as pain, cramping, numbness, or weakness. Nonoperative treatment options for this condition have shown limited success and are often undesirable for the patient given the requirement for activity modification. Traditional surgical treatment options involving open or subcutaneous fasciotomies have more favorable results, but these techniques are associated with significant morbidity. Endoscopically assisted fasciotomy techniques afford the advantages of being minimally invasive, providing excellent visualization, and allowing accelerated rehabilitation. The purpose of this article is to describe a technique for performing endoscopically assisted fasciotomies for chronic exertional compartment syndrome of the lower leg using an entirely endoscopic thermal ablating device. The endoscopic thermal fasciotomy technique is associated with minimal morbidity, ensures excellent hemostasis, and affords an early return to sports. PMID- 26900550 TI - The Subscapularis Interlocking Stitch for the Arthroscopic Treatment of Subscapularis Tendon Tears at the Shoulder. AB - Restoration of subscapularis function is essential for long-term maintenance of good clinical results for both traumatic and nontraumatic rotator cuff tears. The anatomic repair of partially and completely torn tendons from the footprint at the lesser tuberosity is the goal of surgical repair. The described technique, with a combination of an interlocking stitch and additional mattress sutures using a double-loaded suture anchor, provides reduction of the retracted tendon, sufficient pullout strength, and compression of the tendon to the footprint to facilitate healing. PMID- 26900551 TI - Inside-Out Antegrade Tibial Tunnel Drilling Through the Posterolateral Portal Using a Flexible Reamer in Posterior Cruciate Ligament Reconstruction. AB - Posterior cruciate ligament (PCL) reconstruction using the transtibial drilling or arthroscopic tibial-inlay technique has a risk of injury to the popliteal neurovascular bundle because a pin is drilled anterior to posterior. Intraoperative fluoroscopy is used to decrease the risk of neurovascular injury. In addition, graft passage in the transtibial technique may be problematic because of a sharp turn when placing the graft into the tibial tunnel, which may damage graft fibers. In the surgical technique described in this report, the posteromedial portal is used for visualization and the posterolateral portal is used for debridement of the PCL tibial footprint and the synovial fold closest to the PCL. A curved guide is placed from the posterolateral portal to the tibial footprint, and a flexible pin is drilled across the tibia. The tibial tunnel is then created using a flexible reamer under direct visualization up to the desired length, and a graft can be positioned in the tibial tunnel through the posterolateral portal. This technique has the potential advantages of decreasing the risk of injury to the popliteal neurovascular bundle (use of anteriorly directed, inside-out drilling), avoiding a sharp turn during graft passage, and allowing accurate and anatomic tibial tunnel placement without intraoperative fluoroscopy. PMID- 26900544 TI - Microfabricated Systems and Assays for Studying the Cytoskeletal Organization, Micromechanics, and Motility Patterns of Cancerous Cells. AB - Cell motions are driven by coordinated actions of the intracellular cytoskeleton actin, microtubules (MTs) and substrate/focal adhesions (FAs). This coordination is altered in metastatic cancer cells resulting in deregulated and increased cellular motility. Microfabrication tools, including photolithography, micromolding, microcontact printing, wet stamping and microfluidic devices have emerged as a powerful set of experimental tools with which to probe and define the differences in cytoskeleton organization/dynamics and cell motility patterns in non-metastatic and metastatic cancer cells. In this review, we discuss four categories of microfabricated systems: (i) micropatterned substrates for studying of cell motility sub-processes (for example, MT targeting of FAs or cell polarization); (ii) systems for studying cell mechanical properties, (iii) systems for probing overall cell motility patterns within challenging geometric confines relevant to metastasis (for example, linear and ratchet geometries), and (iv) microfluidic devices that incorporate co-cultures of multiple cells types and chemical gradients to mimic in vivo intravasation/extravasation steps of metastasis. Together, these systems allow for creating controlled microenvironments that not only mimic complex soft tissues, but are also compatible with live cell high-resolution imaging and quantitative analysis of single cell behavior. PMID- 26900552 TI - The Double-Pulley Anatomic Technique for Type II SLAP Lesion Repair. AB - The annual incidence and number of repairs of SLAP lesions in the United States are constantly increasing. Surgical repairs of type II SLAP lesions have overall good success rates. However, a low satisfaction rate and low rate of return to preinjury level of play remain a challenge with elite overhead and throwing athletes. Recent anatomic studies suggest that current surgical techniques over tension the biceps anchor and the superior labrum. These studies suggest that restoration of the normal anatomy will improve clinical outcomes and sports performance. We present a "double-pulley" technique for arthroscopic fixation of type II SLAP lesions. In this technique the normal anatomy is respected by preserving the mobility of the articular aspect of the superior labrum while reinforcing the biceps anchor and its posterior fibers medially. PMID- 26900553 TI - Scapulothoracic Endoscopy for the Painful Snapping Scapula: Endoscopic Anatomy and Scapuloplasty Technique. AB - Chronic painful snapping scapula is characterized by inflammation and scarring of 1 or more bursae in the infraserratus space and is often refractory to conservative treatment. Surgical treatment involves excision of the bursae, as well as partial scapulectomy of the superomedial impinging region; both open and endoscopic approaches have been described with good results. Scapulothoracic endoscopy is technically difficult, and the potential complications can be serious. This report describes an endoscopic approach that can be performed with only 2 medial parascapular portals for visualization and instrumentation. The endoscopic anatomy of the infraserratus space is revisited, and 3 anatomic landmarks (serratus anterior, subspinous bursal curtain, and superomedial bony angle) are identified for safe dissection and intraoperative orientation. The surgical field is subdivided into 3 anatomic zones (superomedial space, subspinous space, and scapular bony angle), and the anatomic boundaries of these zones are demonstrated. The decompression procedure is subdivided into 4 stages (superomedial bursectomy, subspinous adhesiolysis, tuberoplasty, and scapuloplasty), and a measured resection technique for scapuloplasty is performed. The use of newer motorized rasps permits optimal bony resection, and additional portals are unnecessary. Overall, the step-by-step technique provides a methodical approach for safety, reproducibility, and optimization of the procedure. PMID- 26900554 TI - Arthroscopic Meniscal Allograft Transplantation With Soft-Tissue Fixation Through Bone Tunnels. AB - Meniscal allograft transplantation improves clinical outcomes for patients with symptomatic meniscus-deficient knees. We describe an established arthroscopic technique for meniscal allograft transplantation without the need for bone fixation of the meniscal horns. After preparation of the meniscal bed, the meniscus is parachuted into the knee through a silicone cannula and the meniscal horns are fixed with sutures through bone tunnels. The body of the meniscus is then fixed with a combination of all-inside and inside-out sutures. This technique is reliable and reproducible and has clinical outcomes comparable with those of bone plug fixation techniques. PMID- 26900555 TI - Arthroscopic Management of Popliteal Tendon Dysfunction in Total Knee Arthroplasty. AB - Unexplainable knee pain may follow knee replacement surgery. The popliteal tendon should be evaluated as a possible cause of lateral knee pain and dysfunction after knee arthroplasty. The tendon can snap over or impinge on lateral osteophytes or prominent femoral components and produce mechanical symptoms and pain. Ultrasound-guided injections may confirm the diagnosis and provide symptomatic relief in some patients. Those who respond well to injections and in whom conservative management ultimately fails may be offered arthroscopic release of the popliteal tendon. We present the arthroscopic technique for popliteal tendon release in a symptomatic patient whose pain resolved immediately postoperatively. We recommend the use of an anterolateral viewing portal and an accessory lateral working portal to access the posterolateral knee. There can be extensive scar tissue overlying the popliteal tendon after arthroplasty. Arthroscopic tendon transection and excision comprise a reliable procedure for popliteal tendon impingement after knee arthroplasty without compromising knee stability. PMID- 26900556 TI - "The Superficial Quad Technique" for Medial Patellofemoral Ligament Reconstruction: The Surgical Video Technique. AB - With the introduction of the superficial quad technique, there has been a recent revival of interest in the quadriceps tendon as a graft choice for medial patellofemoral ligament (MPFL) reconstruction. The superficial quad technique has many anatomic advantages because the length, breadth, and thickness of the graft are similar to those of the native MPFL; moreover, the graft provides a continuous patellar attachment at the superior half of the medial border of the patella. The technique requires neither a patellar bony procedure nor patellar hardware. Biomechanically, the mean strength and stiffness of the graft are very similar to those of the native MPFL. The anatomic and biomechanical advantages depend on correct identification of the anatomic superficial lamina of the quadriceps tendon; hence the correct harvesting technique for the superficial lamina is crucial. Various sub-techniques for harvesting the quadriceps graft have emerged recently, such as superficial strip, pedicled, or partial graft harvesting; these can create confusion for surgeons. Additional confusion related to the preparation and fixation of the graft should also be addressed to avoid any potential complications. A step-by-step video of the superficial quad technique is presented, covering the exact dissection of the graft material and its preparation, delivery, and fixation. PMID- 26900557 TI - Arthroscopic-Assisted Outside-In Repair of Triangular Fibrocartilage Complex Tears. AB - With advances in surgical instrumentation and techniques, as well as expanding surgical indications, wrist arthroscopy is now being used to treat a variety of conditions previously managed only with open techniques. Triangular fibrocartilage complex (TFCC) injuries remain among the most common causes of ulnar-sided wrist pain and can result from both acute and chronic mechanisms of injury. The most common mechanism of acute injury to the TFCC is a fall onto an outstretched hand with the wrist in a supinated, extended position. In patients with unrelenting pain, swelling, or mechanical symptoms despite a concerted effort at nonoperative management, which often consists of bracing, therapy, or injections, surgical intervention is often indicated. Treatment historically consisted of open exploration and repair; however, recently, arthroscopic assisted and all-arthroscopic techniques have been described. We describe a safe, reproducible, and reliable surgical technique for arthroscopic-assisted outside in repair of peripheral TFCC tears. In addition, a specific focus on surgical anatomy, including pearls and pitfalls for protecting the dorsal sensory branch of the ulnar nerve, is presented. PMID- 26900343 TI - Search for single top-quark production via flavour-changing neutral currents at 8 TeV with the ATLAS detector. AB - A search for single top-quark production via flavour-changing neutral current processes from gluon plus up- or charm-quark initial states in proton-proton collisions at the LHC is presented. Data collected with the ATLAS detector in 2012 at a centre-of-mass energy of 8 TeV and corresponding to an integrated luminosity of 20.3 fb[Formula: see text] are used. Candidate events for a top quark decaying into a lepton, a neutrino and a jet are selected and classified into signal- and background-like candidates using a neural network. No signal is observed and an upper limit on the production cross-section multiplied by the [Formula: see text] branching fraction is set. The observed 95 % CL limit is [Formula: see text] and the expected 95 % CL limit is [Formula: see text]. The observed limit can be interpreted as upper limits on the coupling constants of the flavour-changing neutral current interactions divided by the scale of new physics [Formula: see text] and [Formula: see text] and on the branching fractions [Formula: see text] and [Formula: see text]. PMID- 26900558 TI - Arthroscopically Assisted Anatomic Coracoclavicular Ligament Reconstruction Technique Using Coracoclavicular Fixation and Soft-Tissue Grafts. AB - Acromioclavicular joint injuries are common and are often seen in contact athletes. Good to excellent clinical results have been reported using soft-tissue grafts to reconstruct the coracoclavicular ligaments; however, complications remain. Some complications are unique to the surgical technique, particularly clavicle and coracoid fractures that are associated with drilling large or multiple bone tunnels. The described technique allows for an anatomic coracoclavicular reconstruction using a large soft-tissue graft while minimizing the risk of clavicle fracture by avoiding large bone tunnels. PMID- 26900559 TI - Rotator Cerclage Technique for Partial Rotator Cuff Ruptures. AB - The frequency of partial rotator cuff tears is gradually increasing because of the advancements in imaging methods and arthroscopy techniques. One of the repair techniques is repair of the partial rotator cuff tear by conversion to a full thickness tear. Another technique, the transtendon technique, has some practical challenges and risks. We attempted to develop a practical and easy technique with low morbidity to repair partial tears called the rotator cerclage technique. PMID- 26900560 TI - Ankle Arthroscopic Reconstruction of Lateral Ligaments (Ankle Anti-ROLL). AB - Ankle instability is a condition that often requires surgery to stabilize the ankle joint that will improve pain and function if nonoperative treatments fail. Ankle stabilization surgery may be performed as a repair in which the native existing anterior talofibular ligament or calcaneofibular ligament (or both) is imbricated or reattached. Alternatively, when native ankle ligaments are insufficient for repair, a reconstruction of the ligaments may be performed in which an autologous or allograft tendon is used to reconstruct the anterior talofibular ligament or calcaneofibular ligament (or both). Currently, ankle stabilization surgery is most commonly performed through an open incision, but arthroscopic ankle stabilization using repair techniques has been described and is being used more often. We present our technique for anatomic ankle arthroscopic reconstruction of the lateral ligaments (anti-ROLL) performed in an all-inside-out manner that is likely safe for patients and minimally invasive. PMID- 26900561 TI - Medial Patellofemoral Ligament Reconstruction Using a Femoral Loop Button Fixation Technique. AB - Medial patellofemoral ligament (MPFL) reconstruction is a common procedure used to treat both acute and chronic patellar instability. Although many variations of MPFL reconstruction have been described, there is no consensus regarding the optimal surgical technique. We describe a technique for MPFL reconstruction with a looped gracilis tendon autograft using suture anchors to secure the graft to the patella and a suspensory loop button system for fixation to the femur. This technique replicates the native shape of the MPFL while minimizing the risk of patellar fracture and allowing for gradual tensioning of the graft. PMID- 26900562 TI - Enhanced Bone-Tendon-Bone Approach for Open Anterior Cruciate Ligament Replacement With Conservation of the Joint Capsule. AB - Arthroscopic procedures for ruptured anterior cruciate ligament (ACL) tears are a common standard. However, there are strong alternatives to this standard. The purpose of this study is to present a precise, fast, and minimally invasive but open procedure for reconstruction of the ruptured ACL. The torn ACL is substituted by a widely used bone-patellar tendon-bone (BPTB) autograft. After the BPTB graft has been harvested, the Hoffa body is exposed and mobilized ventrally. The surgeon then has a free view of the remnants of the torn ACL, which are to be removed completely. Through the tibial and femoral footprints of the ACL, a tunnel is drilled under a direct view, thus ensuring optimal anatomic positioning of the BPTB graft. The described approach is simple in handling and advantageous because all steps are performed under a direct view, which improves overall precision and intraoperative functional control. PMID- 26900564 TI - All-Inside Posterior Cruciate Ligament Reconstruction: GraftLink Technique. AB - Posterior cruciate ligament (PCL) injuries account for nearly 20% of knee ligament injuries. PCL injuries can occur in isolation or, more commonly, in the setting of multiligamentous knee injuries. Isolated PCL disruptions are commonly treated nonoperatively; however, symptomatic grade III injuries, as well as PCL injuries found in multiligamentous injuries, are frequently treated surgically. Several reconstructive techniques exist for the treatment of PCL deficiency without a clear optimal approach. We describe our preferred operative technique to reconstruct the PCL using an all-inside arthroscopic approach with a quadrupled tibialis anterior or peroneus longus allograft with both tibial and femoral suspensory fixation. PMID- 26900563 TI - Endoscopic Gastrocnemius Intramuscular Aponeurotic Recession. AB - Gastrocnemius aponeurotic recession is the surgical treatment for symptomatic gastrocnemius contracture. Endoscopic gastrocnemius recession procedures has been developed recently and reported to have fewer complications and better cosmetic outcomes. Classically, this is performed at the aponeurosis distal to the gastrocnemius muscle attachment. We describe an alternative endoscopic approach in which the intramuscular portion of the aponeurosis is released. PMID- 26900566 TI - Neural correlates of processing harmonic expectancy violations in children and adolescents with OCD. AB - It has been suggested that patients with obsessive-compulsive disorder (OCD) exhibit enhanced awareness of embedded stimulus patterns as well as enhanced allocation of attention towards unexpected stimuli. Our study aimed at investigating these OCD characteristics by running the harmonic expectancy violation paradigm in 21 boys with OCD and 29 healthy controls matched for age, gender and IQ during a functional magnetic resonance imaging (fMRI) scan. Each trial consisted of a chord sequence in which the first four chords induced a strong expectancy for a harmonic chord at the next position. In 70% of the trials the fifth chord fulfilled this expectancy (harmonic condition), while in 30% the expectancy was violated (disharmonic condition). Overall, the harmonic condition elicited blood-oxygen-level dependent (BOLD) activation in the auditory cortex, while during the disharmonic condition the precuneus, the auditory cortex, the medial frontal gyrus, the premotor cortex, the lingual gyrus, the inferior frontal gyrus and the superior frontal gyrus were activated. In a cluster extending from the right superior temporal gyrus to the inferior frontal gyrus, boys with OCD exhibited increased activation compared to healthy controls in the harmonic condition and decreased activation in the disharmonic condition. Our findings might indicate that patients with OCD are excessively engaged in processing the implicit structure embedded in music stimuli, but they speak against the suggestion that OCD is associated with a misallocation of attention towards the processing of unexpected stimuli. PMID- 26900569 TI - Learning intervention-induced deformations for non-rigid MR-CT registration and electrode localization in epilepsy patients. AB - This paper describes a framework for learning a statistical model of non-rigid deformations induced by interventional procedures. We make use of this learned model to perform constrained non-rigid registration of pre-procedural and post procedural imaging. We demonstrate results applying this framework to non-rigidly register post-surgical computed tomography (CT) brain images to pre-surgical magnetic resonance images (MRIs) of epilepsy patients who had intra-cranial electroencephalography electrodes surgically implanted. Deformations caused by this surgical procedure, imaging artifacts caused by the electrodes, and the use of multi-modal imaging data make non-rigid registration challenging. Our results show that the use of our proposed framework to constrain the non-rigid registration process results in significantly improved and more robust registration performance compared to using standard rigid and non-rigid registration methods. PMID- 26900565 TI - Voxel-based lesion-symptom mapping of stroke lesions underlying somatosensory deficits. AB - The aim of this study was to investigate the relationship between stroke lesion location and the resulting somatosensory deficit. We studied exteroceptive and proprioceptive somatosensory symptoms and stroke lesions in 38 patients with first-ever acute stroke. The Erasmus modified Nottingham Sensory Assessment was used to clinically evaluate somatosensory functioning in the arm and hand within the first week after stroke onset. Additionally, more objective measures such as the perceptual threshold of touch and somatosensory evoked potentials were recorded. Non-parametric voxel-based lesion-symptom mapping was performed to investigate lesion contribution to different somatosensory deficits in the upper limb. Additionally, structural connectivity of brain areas that demonstrated the strongest association with somatosensory symptoms was determined, using probabilistic fiber tracking based on diffusion tensor imaging data from a healthy age-matched sample. Voxels with a significant association to somatosensory deficits were clustered in two core brain regions: the central parietal white matter, also referred to as the sensory component of the superior thalamic radiation, and the parietal operculum close to the insular cortex, representing the secondary somatosensory cortex. Our objective recordings confirmed findings from clinical assessments. Probabilistic tracking connected the first region to thalamus, internal capsule, brain stem, postcentral gyrus, cerebellum, and frontal pathways, while the second region demonstrated structural connections to thalamus, insular and primary somatosensory cortex. This study reveals that stroke lesions in the sensory fibers of the superior thalamocortical radiation and the parietal operculum are significantly associated with multiple exteroceptive and proprioceptive deficits in the arm and hand. PMID- 26900568 TI - Regional brain stiffness changes across the Alzheimer's disease spectrum. AB - Magnetic resonance elastography (MRE) is an MRI-based technique to noninvasively measure tissue stiffness. Currently well established for clinical use in the liver, MRE is increasingly being investigated to measure brain stiffness as a novel biomarker of a variety of neurological diseases. The purpose of this work was to apply a recently developed MRE pipeline to measure regional brain stiffness changes in human subjects across the Alzheimer's disease (AD) spectrum, and to gain insights into the biological processes underlying those stiffness changes by correlating stiffness with existing biomarkers of AD. The results indicate that stiffness changes occur mostly in the frontal, parietal and temporal lobes, in accordance with the known topography of AD pathology. Furthermore, stiffness in those areas correlates with existing imaging biomarkers of AD including hippocampal volumes and amyloid PET. Additional analysis revealed preliminary but significant evidence that the relationship between brain stiffness and AD severity is nonlinear and non-monotonic. Given that similar relationships have been observed in functional MRI experiments, we used task-free fMRI data to test the hypothesis that brain stiffness was sensitive to structural changes associated with altered functional connectivity. The analysis revealed that brain stiffness is significantly and positively correlated with default mode network connectivity. Therefore, brain stiffness as measured by MRE has potential to provide new and essential insights into the temporal dynamics of AD, as well as the relationship between functional and structural plasticity as it relates to AD pathophysiology. PMID- 26900567 TI - Dissociation of working memory impairments and attention-deficit/hyperactivity disorder in the brain. AB - Prevailing neuropsychological models of attention-deficit/hyperactivity disorder (ADHD) propose that ADHD arises from deficits in executive functions such as working memory, but accumulating clinical evidence suggests a dissociation between ADHD and executive dysfunctions. This study examined whether ADHD and working memory capacity are behaviorally and neurobiologically separable using functional magnetic resonance imaging (fMRI). Participants diagnosed with ADHD in childhood who subsequently remitted or persisted in their diagnosis as adults were characterized at follow-up in adulthood as either impaired or unimpaired in spatial working memory relative to controls who never had ADHD. ADHD participants with impaired spatial working memory performed worse than controls and ADHD participants with unimpaired working memory during an n-back working memory task while being scanned. Both controls and ADHD participants with unimpaired working memory exhibited significant linearly increasing activation in the inferior frontal junction, precuneus, lingual gyrus, and cerebellum as a function of working-memory load, and these activations did not differ significantly between these groups. ADHD participants with impaired working memory exhibited significant hypoactivation in the same regions, which was significantly different than both control participants and ADHD participants with unimpaired working memory. These findings support both a behavioral and neurobiological dissociation between ADHD and working memory capacity. PMID- 26900571 TI - Sexually dimorphic brain volume interaction in college-aged binge drinkers. AB - BACKGROUND: Binge consumption of alcohol is a major societal problem associated with important cognitive, physiological and neurotoxic consequences. Converging evidence highlights the need to assess binge drinking (BD) and its effects on the developing brain while taking into account gender differences. Here, we compared the brain volumetric differences between genders in college-aged binge drinkers and healthy volunteers. METHOD: T1-weighted magnetic resonance imaging (MRI) images of 30 binge drinkers (18 males) and 46 matched healthy volunteers (23 males) were examined using voxel-based morphometry. The anatomical scans were covaried with Alcohol Use Disorders Identification Test (AUDIT) scores. Whole brain voxel-wise group comparisons were performed using a cluster extent threshold correction. RESULTS: Several large clusters qualified with group-by gender interactions were observed in prefrontal, striatal and medial temporal areas, whereby BD females had more volume than non-BD females, while males showed the inverse pattern of decreased volume in BD males and increased volume in non BD males. AUDIT scores negatively correlated with volume in the right superior frontal cortex and precentral gyrus. CONCLUSIONS: These findings dovetail with previous studies reporting that a state effect of BD in college-aged drinkers and the severity of alcohol use are associated with volumetric alterations in the cortical and subcortical areas of the brain. Our study indicates that these widespread volumetric changes vary differentially by gender, suggesting either sexual dimorphic endophenotypic risk factors, or differential neurotoxic sensitivities for males and females. PMID- 26900570 TI - Functional network topology associated with posttraumatic stress disorder in veterans. AB - Posttraumatic stress disorder (PTSD) is a disabling disorder associated with resting state functional connectivity alterations. However, whether specific brain regions are altered in PTSD or whether the whole brain network organization differs remains unclear. PTSD can be treated with trauma-focused therapy, although only half of the patients recover after treatment. In order to better understand PTSD psychopathology our aim was to study resting state networks in PTSD before and after treatment. Resting state functional magnetic resonance images were obtained from veterans with PTSD (n = 50) and controls (combat and civilian controls; n = 54) to explore which network topology properties (degree and clustering coefficient) of which brain regions are associated with PTSD. Then, PTSD-associated brain regions were investigated before and after treatment. PTSD patients were subdivided in persistent (n = 22) and remitted PTSD patients (n = 17), and compared with combat controls (n = 22), who were also reassessed. Prior to treatment associations with PTSD were found for the degree of orbitofrontal, and temporoparietal brain regions, and for the clustering coefficient of the anterior cingulate cortex. No significant effects were found over the course of treatment. Our results are in line with previous resting state studies, showing resting state connectivity alterations in the salience network and default mode network in PTSD, and also highlight the importance of other brain regions. However, network metrics do not seem to change over the course of treatment. This study contributes to a better understanding of the psychopathology of PTSD. PMID- 26900572 TI - Detectability of the somatosensory evoked high frequency oscillation (HFO) co recorded by scalp EEG and ECoG under propofol. AB - OBJECTIVE: The somatosensory evoked potential (SEP) elicited by median nerve stimulation consists of the N20 peak together with the concurrent high frequency oscillation (HFO, > 500 Hz). We describe the conditions for HFO detection in ECoG and scalp EEG in intraoperative recordings. METHODS: During neurosurgical interventions in six patients under propofol anesthesia, the SEP was recorded from subdural electrode strips (15 recordings) and from scalp electrodes (10/15 recordings). We quantified the spatial attenuation of the Signal-to-Noise Ratio (SNR) of N20 and HFO along the contacts of the electrode strip. We then compared the SNR of ECoG and simultaneous scalp EEG in a biophysical framework. RESULTS: HFO detection under propofol anesthesia was demonstrated. Visual inspection of strip cortical recordings revealed phase reversal for N20 in 14/15 recordings and for HFO in 10/15 recordings. N20 had higher maximal SNR (median 33.5 dB) than HFO (median 23 dB). The SNR of N20 attenuated with a larger spatial extent (median 7.2 dB/cm) than the SNR of HFO (median 12.3 dB/cm). We found significant correlations between the maximum SNR (rho = 0.58, p = 0.025) and the spatial attenuation (rho = 0.86, p < 0.001) of N20 and HFO. In 3/10 recordings we found HFO in scalp EEG. Based on the spatial attenuation and SNR in the ECoG, we estimated the scalp EEG amplitude ratio N20/HFO and found significant correlation with recorded values (rho = 0.65, p = 0.049). CONCLUSIONS: We proved possible the intraoperative SEP HFO detection under propofol anesthesia. The spatial attenuation along ECoG contacts represents a good estimator of the area contributing to scalp EEG. The SNR and the spatial attenuation in ECoG recordings provide further insights for the prediction of HFO detectability in scalp EEG. The results obtained in this context may not be limited to SEP HFO, but could be generalized to biological signatures lying in the same SNR and frequency range. PMID- 26900573 TI - Building laboratory capacity to support HIV care in Nigeria: Harvard/APIN PEPFAR, 2004-2012. AB - INTRODUCTION: From 2004-2012, the Harvard/AIDS Prevention Initiative in Nigeria, funded through the US President's Emergency Plan for AIDS Relief programme, scaled up HIV care and treatment services in Nigeria. We describe the methodologies and collaborative processes developed to improve laboratory capacity significantly in a resource-limited setting. These methods were implemented at 35 clinic and laboratory locations. METHODS: Systems were established and modified to optimise numerous laboratory processes. These included strategies for clinic selection and management, equipment and reagent procurement, supply chains, laboratory renovations, equipment maintenance, electronic data management, quality development programmes and trainings. RESULTS: Over the eight-year programme, laboratories supported 160 000 patients receiving HIV care in Nigeria, delivering over 2.5 million test results, including regular viral load quantitation. External quality assurance systems were established for CD4+ cell count enumeration, blood chemistries and viral load monitoring. Laboratory equipment platforms were improved and standardised and use of point-of-care analysers was expanded. Laboratory training workshops supported laboratories toward increasing staff skills and improving overall quality. Participation in a World Health Organisation-led African laboratory quality improvement system resulted in significant gains in quality measures at five laboratories. CONCLUSIONS: Targeted implementation of laboratory development processes, during simultaneous scale-up of HIV treatment programmes in a resource limited setting, can elicit meaningful gains in laboratory quality and capacity. Systems to improve the physical laboratory environment, develop laboratory staff, create improvements to reduce costs and increase quality are available for future health and laboratory strengthening programmes. We hope that the strategies employed may inform and encourage the development of other laboratories in resource-limited settings. PMID- 26900575 TI - Hypoxia inducible factor-1 alpha and multiple myeloma. AB - Rapid tumor growth creates a state of hypoxia in the tumor microenvironment and results in release of hypoxia inducible factor-1 alpha (HiF-1alpha) in the local milieu. Hypoxia inducible factor activity is deregulated in many human cancers, especially those that are highly hypoxic. In multiple myeloma (MM) in initial stages of disease establishment, the hypoxic bone marrow microenvironment supports the initial survival and growth of the myeloma cells. Hypoxic tumour cells are usually resistant to radiotherapy and most conventional chemotherapeutic agents, rendering them highly aggressive and metastatic. Therefore, HIF is an attractive, although challenging, therapeutic target in MM directly or indirectly in recent years. PMID- 26900576 TI - Clinical Care Pathways for Patients With Hepatitis C: Reducing Critical Barriers to Effective Treatment. AB - Background. Engagement of individuals infected with hepatitis C virus (HCV) with care pathways remains a major barrier to realizing the benefits of new and more effective antiviral therapies. After an exploratory study, we have undertaken an evidence-based redesign of care pathways for HCV, including the following: (1) reflex testing of anti-HCV-positive samples for HCV RNA; (2) annotation of laboratory results to recommend referral of actively infected patients to specialist clinics; (3) educational programs for primary care physicians and nurses; and (4) the establishment of needs-driven community clinics in substance misuse services. Methods. In this study, we conducted a retrospective cohort study of progression through care pathways of individuals with a new diagnosis of HCV infection made between January 2010 and January 2012. We also analyzed patient flow through new care pathways and compared this with our baseline study of identical design. Results. A total of 28 980 samples were tested for anti-HCV antibody during the study period and yielded 273 unique patients with a new diagnosis of HCV infection. Of these, 38% were tested in general practice, 21% were tested in substance misuse services, 23% were tested in secondary care, and 18% were tested in local prisons. Overall, 80% of patients were referred to specialist clinics, 70% attended for assessment, and 38% commenced treatment, in comparison to 49%, 27%, and 10%, respectively, in the baseline study. Referral rates from all testing sources improved. Conclusions. This study provides timely evidence that progression through care pathways can be enhanced, and it demonstrates reduction of key barriers to eradication of HCV. PMID- 26900574 TI - Dietary Factors and Cognitive Decline. AB - Cognitive decline is an increasingly important public health problem, with more than 100 million adults worldwide projected to develop dementia by 2050. Accordingly, there has been an increased interest in preventive strategies that diminish this risk. It has been recognized that lifestyle factors including dietary patterns, may be important in the prevention of cognitive decline and dementia in later life. Several dietary components have been examined, including antioxidants, fatty acids, and B vitamins. In addition, whole dietary eating plans, including the Mediterranean diet (MeDi), and the Dietary Approaches to Stop Hypertension (DASH) diet, with and without weight loss, have become areas of increasing interest. Although prospective epidemiological studies have observed that antioxidants, fatty acids, and B vitamins are associated with better cognitive functioning, randomized clinical trials have generally failed to confirm the value of any specific dietary component in improving neurocognition. Several randomized trials have examined the impact of changing 'whole' diets on cognitive outcomes. The MeDi and DASH diets offer promising preliminary results, but data are limited and more research in this area is needed. PMID- 26900577 TI - Molecular Epidemiology of Rhinovirus Detections in Young Children. AB - Background. Human rhinoviruses (HRVs) are frequently detected in children with acute respiratory illnesses (ARIs) but also in asymptomatic children. We compared features of ARI with HRV species (A, B, C) and determined genotypes associated with repeated HRV detections within individuals. Methods. We used clinical data and respiratory samples obtained from children <3 years old during weekly active household-based surveillance. A random subset of samples in which HRV was detected from individuals during both ARI and an asymptomatic period within 120 days of the ARI were genotyped. Features of ARI were compared among HRV species. Concordance of genotype among repeated HRV detections within individuals was assessed. Results. Among 207 ARI samples sequenced, HRV-A, HRV-B, and HRV-C were detected in 104 (50%), 20 (10%), and 83 (40%), respectively. Presence of fever, decreased appetite, and malaise were significantly higher in children with HRV-B. When codetections with other viruses were excluded (n = 155), these trends persisted, but some did not reach statistical significance. When 58 paired sequential HRV detections during asymptomatic and ARI episodes were sequenced, only 9 (16%) were identical genotypes of HRV. Conclusions. Clinical features may differ among HRV species. Repeated HRV detections in young children frequently represented acquisition of new HRV strains. PMID- 26900578 TI - "Central vessel sign" on 3T FLAIR* MRI for the differentiation of multiple sclerosis from migraine. AB - OBJECTIVE: The diagnosis of multiple sclerosis (MS) presently relies on radiographic assessments of imperfect specificity. Recent data using T2* methodology for the detection of the "central vessel sign" (CVS) in MS lesions suggests this novel MRI technique may distinguish MS from other disorders. Our aim was to determine if evaluation for CVS on 3T FLAIR* MRI differentiates MS from migraine. METHODS: Patients with MS or migraine and a prior brain MRI demonstrating at least two hyperintense lesions >=3 mm were recruited. Exclusion criteria included any additional comorbidity known to cause brain MRI abnormalities. 3T MRI was performed in each participant with administration of gadopentetate dimeglumine, and FLAIR* images were generated in postprocessing. The total number of discrete ovoid lesions >=3 mm were counted on FLAIR, per participant, and subsequently evaluated for presence of CVS on FLAIR*. An exploratory method evaluating for CVS in a maximum of 12 lesions per subject was also completed. RESULTS: Ten participants with MS and 10 with migraine completed the study. The median percentage (quartiles) of lesions in MS participants with CVS was 84 (79, 94) compared to 22 (15, 54) in migraine (P = 0.008). In a subanalysis by brain region, in the subcortical and deep white matter, the median percentage (quartiles) of lesions in MS participants with CVS was 88 (81, 100) compared to 19 (11, 54) in migraine (P = 0.004). This difference was not identified in juxtacortical, periventricular, or infratentorial regions. INTERPRETATION: Identification of CVS using FLAIR* on 3T MRI helps differentiate MS from migraine, particularly in the subcortical and deep white matter. PMID- 26900579 TI - Corneal confocal microscopy in chronic inflammatory demyelinating polyneuropathy. AB - OBJECTIVE: There is an unmet need for better diagnostic tools to further delineate clinical subsets of heterogeneous chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN) to facilitate treatment decisions. Corneal confocal microscopy (CCM) is a noninvasive and reproducible nerve imaging technique. This study evaluates the potential of CCM as a diagnostic surrogate in CIDP and MMN. METHODS: In a cross-sectional prospective approach, 182 patients and healthy controls were studied using CCM to quantify corneal nerve damage and immune cell infiltration. RESULTS: Patients with CIDP and MMN had a reduction in corneal nerve fiber (CNF) measures and an increase in corneal immune cell infiltrates. In CIDP, CNF parameters decreased with increasing duration of disease. The number of dendritic cells in proximity to CNFs was increased in patients with early disease and correlated with the degree of motor affection. A further reduction in CNF parameters and an increase in nondendritic cells were observed in patients with painful neuropathy. In CIDP patients with antineuronal antibodies the number of nondendritic cells was increased. INTERPRETATION: Our findings suggest that CNF loss may reflect severity of neuropathy and quantification of distinct cells around the CNF plexus may help in stratifying CIDP subtypes, clinical course, and disease activity. However, further longitudinal studies are required before CCM can be considered as a valid surrogate endpoint for patients with CIDP and MMN. PMID- 26900580 TI - Pathogenic mechanism of recurrent mutations of SCN8A in epileptic encephalopathy. AB - OBJECTIVE: The early infantile epileptic encephalopathy type 13 (EIEE13, OMIM #614558) results from de novo missense mutations of SCN8A encoding the voltage gated sodium channel Nav1.6. More than 20% of patients have recurrent mutations in residues Arg1617 or Arg1872. Our goal was to determine the functional effects of these mutations on channel properties. METHODS: Clinical exome sequencing was carried out on patients with early-onset seizures, developmental delay, and cognitive impairment. Two mutations identified here, p.Arg1872Leu and p.Arg1872Gln, and two previously identified mutations, p.Arg1872Trp and p.Arg1617Gln, were introduced into Nav1.6 cDNA, and effects on electrophysiological properties were characterized in transfected ND7/23 cells. Interactions with FGF14, G-protein subunit Gbetagamma, and sodium channel subunit beta1 were assessed by coimmunoprecipitation. RESULTS: We identified two patients with the novel mutation p.Arg1872Leu and one patient with the recurrent mutation p.Arg1872Gln. The three mutations of Arg1872 and the mutation of Arg1617 all impaired the sodium channel transition from open state to inactivated state, resulting in channel hyperactivity. Other observed abnormalities contributing to elevated channel activity were increased persistent current, increased peak current density, hyperpolarizing shift in voltage dependence of activation, and depolarizing shift in steady-state inactivation. Protein interactions were not affected. INTERPRETATION: Recurrent mutations at Arg1617 and Arg1872 lead to elevated Nav1.6 channel activity by impairing channel inactivation. Channel hyperactivity is the major pathogenic mechanism for gain-of-function mutations of SCN8A. EIEE13 differs mechanistically from Dravet syndrome, which is caused by loss-of-function mutations of SCN1A. This distinction has important consequences for selection of antiepileptic drugs and the development of gene- and mutation specific treatments. PMID- 26900582 TI - A LRSAM1 mutation links Charcot-Marie-Tooth type 2 to Parkinson's disease. AB - LRSAM1 mutations have been found in recessive and dominant forms of Charcot-Marie Tooth disease. Within one generation of the original Dutch family in which the dominant LRSAM1 mutation was identified, three of the five affected family members have developed Parkinson's disease between ages 50 and 65 years, many years after neuropathy onset. We speculate that this late-onset parkinsonism is part of the LRSAM1 phenotype, thus associating a hitherto peripheral nerve disease with a central nervous system phenotype. How the mutated Lrsam1 protein, which normally has E3 ubiquitin ligase activity and is expressed in the nervous system, impacts on substantia nigra neurons is unclear. PMID- 26900581 TI - Reduced brain connectivity and mental flexibility in mild traumatic brain injury. AB - OBJECTIVE: A mild traumatic brain injury (mTBI), or concussion, has known neuropsychological sequelae, and neuroimaging shows disturbed brain connectivity during the resting state. We hypothesized that task-based functional connectivity measures, using magnetoencephalography (MEG), would better link the neurobiological underpinnings of cognitive deficits to specific brain damage. METHODS: We used a mental flexibility task in the MEG and compared brain connectivity between adults with and without mTBI. RESULTS: Affected individuals showed significant reductions in connectivity. When challenged with a more difficult task, these individuals were not able to "boost" their connectivity, and as such, showed deterioration in performance. INTERPRETATION: We discuss these findings in the context of limitations in cognitive reserve as a consequence of a mTBI. PMID- 26900583 TI - Blood transcriptome changes after stroke in an African American population. AB - OBJECTIVE: Molecular diagnostic medicine holds much promise to change point of care treatment. An area where additional diagnostic tools are needed is in acute stroke care, to assist in diagnosis and prognosis. Previous studies using microarray-based gene expression analysis of peripheral blood following stroke suggests this approach may be effective. Next-generation sequencing (NGS) approaches have expanded genomic analysis and are not limited to previously identified genes on a microarray chip. Here, we report on a pilot NGS study to identify gene expression and exon expression patterns for the prediction of stroke diagnosis and prognosis. METHODS: We recruited 28 stroke patients and 28 age- and sex-matched hypertensive controls. RNA was extracted from 3 mL blood samples, and RNA-Seq libraries were assembled and sequenced. RESULTS: Bioinformatical analysis of the aligned RNA data reveal exonic (30%), intronic (36%), and novel RNA components (not currently annotated: 33%). We focused our study on patients with confirmed middle cerebral artery occlusion ischemic stroke (n = 17). On the basis of our observation of differential splicing of gene transcripts, we used all exonic RNA expression rather than gene expression (combined exons) to build prediction models using support vector machine algorithms. Based on model building, these models have a high predicted accuracy rate >90% (spec. 88% sen. 92%). We further stratified outcome based on the improvement in NIHss scores at discharge; based on model building we observe a predicted 100% accuracy rate. INTERPRETATION: NGS-based exon expression analysis approaches have a high potential for patient diagnosis and outcome prediction, with clear utility to aid in clinical patient care. PMID- 26900584 TI - Altered paired associative stimulation-induced plasticity in NMDAR encephalitis. AB - OBJECTIVE: To determine whether neurophysiological mechanisms indicating cortical excitability, long-term potentiation (LTP)-like plasticity, GABAergic and glutamatergic function are altered in patients with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis and whether they can be helpful as markers of diagnostic assessment, disease progression, and potentially therapy response. METHODS: Neurophysiological characterizations of patients with NMDAR encephalitis (n = 34, mean age: 28 +/- 11 years; 30 females) and age/gender-matched healthy controls (n = 27, 28.5 +/- 10 years; 25 females) were performed using transcranial magnetic stimulation-derived protocols including resting motor threshold, recruitment curve, intracortical facilitation, short intracortical inhibition, and cortical silent period. Paired associative stimulation (PAS) was applied to assess LTP-like mechanisms which are mediated through NMDAR. Moreover, resting state functional connectivity was determined using functional magnetic resonance imaging. RESULTS: PAS-induced plasticity differed significantly between groups (P = 0.0056). Cortical excitability, as assessed via motor-evoked potentials after PAS, decreased in patients, whereas it increased in controls indicating malfunctioning of NMDAR in encephalitis patients. Lower PAS-induced plasticity significantly correlated with the modified Rankin Scale (mRS) (r = 0.41; P = 0.0031) and was correlated with lower functional connectivity within the motor network in NMDAR encephalitis patients (P < 0.001, uncorrected). Other neurophysiological parameters were not significantly different between groups. Follow-up assessments were available in six patients and demonstrated parallel improvement of PAS-induced plasticity and mRS. INTERPRETATION: Assessment of PAS induced plasticity may help to determine NMDAR dysfunction and disease severity in NMDAR encephalitis, and might even aid as a sensitive, noninvasive, and well tolerated "electrophysiological biomarker" to monitor therapy response in the future. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: Identifier: NCT01865578. PMID- 26900587 TI - Primary Care Clinics and Accountable Care Organizations. AB - BACKGROUND: The Accountable Care Organization (ACO) is one of the new models of health care delivery in the U.S. To date, little is known about the characteristics of health care organizations that have joined ACOs. We report on the findings of a survey of primary care clinics, the objective of which was to investigate the opinions of clinic management about participation in ACOs, and the characteristics of clinic organizational structure that may contribute to joining ACOs or be willing to do so. METHODS: A 27-item survey questionnaire was developed and distributed by mail in 3 annual waves to all Rural Health Clinics (RHCs) in 9 states. Two dependent variables - participation in ACOs and willingness to join ACOs - were created and analyzed using a generalized estimating equation (GEE) approach. RESULTS: 257 RHCs responded to the survey. A small percentage (5.2%) of the respondent clinics reported that they were participating in ACOs. RHCs in isolated areas were 78% less likely to be in ACOs (odds= 0.22, p= 0.059). Non-profit RHCs indicated a higher willingness to join an ACO than for-profit RHCs (B= 1.271, p= 0.054). There is a positive relationship between RHC size and willingness to join an ACO (B= 0.402, p=0.010). CONCLUSIONS: At this early stage of ACO development, many RHC personnel are unfamiliar with the ACO model. Rural providers' limited technological and human resources, and the lack of ACO development in rural areas, may delay or prevent their participation in ACOs. PMID- 26900586 TI - Implications of Childhood Experiences for the Health and Adaptation of Lesbian, Gay, and Bisexual Individuals: Sensitivity to Developmental Process in Future Research. AB - The empirical literature on lesbian, gay, and bisexual (LGB) individuals has predominantly focused on sexual-orientation disparities between LGB and heterosexual individuals on health and adaptation, as well as on the role of gay related or minority stress in the health and adaptation of LGB individuals. Aside from demographic control variables, the initial predictor is a marker of sexual orientation or LGB-related experience (e.g., minority stress). Missing are potential strengths and vulnerabilities that LGB individuals develop over time and bring to bear on their sexual identity development and other LGB-related experiences. Those strengths and vulnerabilities may have profound consequences for the sexual identity development, health, and adaptation of LGB individuals. Here, I focus on one such set of strengths and vulnerabilities derived from attachment. I conclude by emphasizing the importance of attachment in the lives of LGB individuals and the need to identify other developmental processes that may be equally consequential. PMID- 26900588 TI - Authentication of experimental materials: A remedy for the reproducibility crisis? PMID- 26900585 TI - Baseline results of the NeuroNEXT spinal muscular atrophy infant biomarker study. AB - OBJECTIVE: This study prospectively assessed putative promising biomarkers for use in assessing infants with spinal muscular atrophy (SMA). METHODS: This prospective, multi-center natural history study targeted the enrollment of SMA infants and healthy control infants less than 6 months of age. Recruitment occurred at 14 centers within the NINDS National Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT) Network. Infant motor function scales and putative electrophysiological, protein and molecular biomarkers were assessed at baseline and subsequent visits. RESULTS: Enrollment began November, 2012 and ended September, 2014 with 26 SMA infants and 27 healthy infants enrolled. Baseline demographic characteristics of the SMA and control infant cohorts aligned well. Motor function as assessed by the Test for Infant Motor Performance Items (TIMPSI) and the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) revealed significant differences between the SMA and control infants at baseline. Ulnar compound muscle action potential amplitude (CMAP) in SMA infants (1.4 +/- 2.2 mV) was significantly reduced compared to controls (5.5 +/- 2.0 mV). Electrical impedance myography (EIM) high frequency reactance slope (Ohms/MHz) was significantly higher in SMA infants than controls SMA infants had lower survival motor neuron (SMN) mRNA levels in blood than controls, and several serum protein analytes were altered between cohorts. INTERPRETATION: By the time infants were recruited and presented for the baseline visit, SMA infants had reduced motor function compared to controls. Ulnar CMAP, EIM, blood SMN mRNA levels, and serum protein analytes were able to distinguish between cohorts at the enrollment visit. PMID- 26900589 TI - Anonymous nuclear markers data supporting species tree phylogeny and divergence time estimates in a cactus species complex in South America. AB - Supportive data related to the article "Anonymous nuclear markers reveal taxonomic incongruence and long-term disjunction in a cactus species complex with continental-island distribution in South America" (Perez et al., 2016) [1]. Here, we present pyrosequencing results, primer sequences, a cpDNA phylogeny, and a species tree phylogeny. PMID- 26900590 TI - Energy audit data for a resort island in the South China Sea. AB - The data consists of actual generation-side auditing including the distribution of loads, seasonal load profiles, and types of loads as well as an analysis of local development planning of a resort island in the South China Sea. The data has been used to propose an optimal combination of hybrid renewable energy systems that able to mitigate the diesel fuel dependency on the island. The resort island selected is Tioman, as it represents the typical energy requirements of many resort islands in the South China Sea. The data presented are related to the research article "Optimal Combination of Solar, Wind, Micro Hydro and Diesel Systems based on Actual Seasonal Load Profiles for a Resort Island in the South China Sea" [1]. PMID- 26900591 TI - Tree traits and canopy closure data from an experiment with 34 planted species native to Sabah, Borneo. AB - The data presented in this paper is supporting the research article "Life history traits predict the response to increased light among 33 tropical rainforest tree species" [3]. We show basic growth and survival data collected over the 6 years duration of the experiment, as well as data from traits inventories covering 12 tree traits collected prior to and after a canopy reduction treatment in 2013. Further, we also include canopy closure and forest light environment data from measurements with hemispherical photographs before and after the treatment. PMID- 26900592 TI - Exploratory factor structure of the neurological evaluation scale in black africans with first episode schizophrenia. AB - While the organization of neurological soft signs (NSS) in schizophrenia into Sensory integration, Motor coordination, and Motor sequencing, is functionally 'meaningful', it has not been confirmed by empirical methods such as factor analysis. Data on the exploratory factor analysis of the Neurological Evaluation scale in Black Africans with first episode schizophrenia are presented in this report. Data on the confirmatory factor structure of NSS in this population as well as their interpretation can be found in the work by Ojagbemi et al. (2015) [7]. PMID- 26900593 TI - Data supporting mitochondrial morphological changes by SPG13-associated HSPD1 mutants. AB - The data is related to the research article entitled "Hypomyelinating leukodystrophy-associated missense mutation in HSPD1 blunts mitochondrial dynamics" [1]. In addition to hypomyelinating leukodystrophy (HLD) 4 (OMIM no. 612233), it is known that spastic paraplegia (SPG) 13 (OMIM no. 605280) is caused by HSPD1's amino acid mutation. Two amino acid mutations Val-98-to-Ile (V98I) and Gln-461-to-Glu (Q461E) are associated with SPG13 [2]. In order to investigate the effects of HSPD1's V98I or Q461E mutant on mitochondrial morphological changes, we transfected each of the respective mutant-encoding genes into Cos-7 cells. Either of V98I or Q461E mutant exhibited increased number of mitochondria and short length mitochondrial morphologies. Using MitoTracker dye-incorporating assay, decreased mitochondrial membrane potential was also observed in both cases. The data described here supports that SPG13-associated HSPD1 mutant participates in causing aberrant mitochondrial morphological changes with decreased activities. PMID- 26900594 TI - Thermodynamic database for the Co-Pr system. AB - In this article, we describe data on (1) compositions for both as-cast and heat treated specimens were summarized in Table 1; (2) the determined enthalpy of mixing of liquid phase is listed in Table 2; (3) thermodynamic database of the Co Pr system in TDB format for the research articled entitle Chemical partitioning for the Co-Pr system: First-principles, experiments and energetic calculations to investigate the hard magnetic phase W. PMID- 26900595 TI - Personal and ambient PM2.5 exposure assessment in the city of Agra. AB - Human exposure to fine particles can have significant harmful effects on the respiratory and cardiovascular system. To investigate daily exposure characteristics to PM2.5 with ambient concentrations in an urban environment, a personal exposure measurements were conducted for school children, office workers and at their residents, in the city of Taj 'Agra', India. In order to account for all the sources of particulate matter exposure, measurements on several different days during December 2013 to February 2014 were carried out. Personal environment monitors (PEM) and APM 550 were used to measure PM2.5 concentration. The research findings provide insight into possible sources and their interaction with human activities in modifying the human exposure levels. PMID- 26900596 TI - Data supporting the role of enzymes and polysaccharides during cassava postharvest physiological deterioration. AB - This data article is referred to the research article entitled The role of ascorbate peroxidase, guaiacol peroxidase, and polysaccharides in cassava (Manihot esculenta Crantz) roots under postharvest physiological deterioration by Uarrota et al. (2015). Food Chemistry 197, Part A, 737-746. The stress duo to PPD of cassava roots leads to the formation of ROS which are extremely harmful and accelerates cassava spoiling. To prevent or alleviate injuries from ROS, plants have evolved antioxidant systems that include non-enzymatic and enzymatic defence systems such as ascorbate peroxidase, guaiacol peroxidase and polysaccharides. In this data article can be found a dataset called "newdata", in RData format, with 60 observations and 06 variables. The first 02 variables (Samples and Cultivars) and the last 04, spectrophotometric data of ascorbate peroxidase, guaiacol peroxidase, tocopherol, total proteins and arcsined data of cassava PPD scoring. For further interpretation and analysis in R software, a report is also provided. Means of all variables and standard deviations are also provided in the Supplementary tables ("data.long3.RData, data.long4.RData and meansEnzymes.RData"), raw data of PPD scoring without transformation (PPDmeans.RData) and days of storage (days.RData) are also provided for data analysis reproducibility in R software. PMID- 26900597 TI - A Biosynthetic Scaffold that Facilitates Chondrocyte-Mediated Degradation and Promotes Articular Cartilage Extracellular Matrix Deposition. AB - Articular cartilage remains a significant clinical challenge to repair because of its limited self-healing capacity. Interest has grown in the delivery of autologous chondrocytes to cartilage defects, and combining cell-based therapies with scaffolds that capture aspects of native tissue and allow cell-mediated remodeling could improve outcomes. Currently, scaffold-based therapies with encapsulated chondrocytes permit matrix production; however, resorption of the scaffold often does not match the rate of matrix production by chondrocytes, which can limit functional tissue regeneration. Here, we designed a hybrid biosynthetic system consisting of poly (ethylene glycol) (PEG) endcapped with thiols and crosslinked by norbornene-functionalized gelatin via a thiol-ene photopolymerization. The protein crosslinker was selected to facilitate chondrocyte-mediated scaffold remodeling and matrix deposition. Gelatin was functionalized with norbornene to varying degrees (~4-17 norbornenes/gelatin), and the shear modulus of the resulting hydrogels was characterized (<0.1-0.5 kPa). Degradation of the crosslinked PEG-gelatin hydrogels by chondrocyte secreted enzymes was confirmed by gel permeation chromatography. Finally, chondrocytes encapsulated in these biosynthetic scaffolds showed significantly increased glycosaminoglycan deposition over just 14 days of culture, while maintaining high levels of viability and producing a distributed matrix. These results indicate the potential of a hybrid PEG-gelatin hydrogel to permit chondrocyte-mediated remodeling and promote articular cartilage matrix production. Tunable scaffolds that can easily permit chondrocyte-mediated remodeling may be useful in designing treatment options for cartilage tissue engineering applications. PMID- 26900599 TI - A Randomized Controlled Trial of a Mobile Medical App for Kidney Transplant Recipients: Effect on Use of Sun Protection. AB - BACKGROUND: Perception of skin cancer risk, belief that sun protection prevents skin cancer, and having sun protection choices enhance sun protection behaviors by kidney transplant recipients, who are at greater risk of developing skin cancer than the general population. METHODS: A randomized controlled trial used stratified recruitment of non-Hispanic White, non-Hispanic Black, and Hispanic/Latino kidney transplant recipients, who received a transplant 2-24 months prior to the study. The same culturally sensitive SunProtectTM program was delivered to all recipients with tablet personal computers in two urban ambulatory offices. Text messages reminders were provided at two week intervals. Self-reported surveys and skin pigmentation measured prior to the intervention and six weeks later were analyzed. RESULTS: Among 552 eligible participants, 170 participated (62 non-Hispanic Whites, 60Blacks, and 48 Hispanics). Among participants receiving the intervention with skin that burns after sun exposure and becomes tan or becomes irritated and gets darker, there was a statistically significant increase in self-reported knowledge, recognition of personal skin cancer risk, confidence in sun protection preventing skin cancer, and sun protection behaviors in participants compared to those receiving usual education (p<0.05). At the six week follow-up, participants in the intervention group with skin that burns or becomes irritated, had significantly less darkening of the sun exposed forearm than control participants (p<0.05). CONCLUSIONS: Providing sun protection education with SunProtectTM in the springwith reminders during the summer facilitated adoption of sun protection behaviors among kidney transplant recipients with skin that burns or becomes irritated. PMID- 26900598 TI - Evaluation of polymer shielding for adenovirus serotype 6 (Ad6) for systemic virotherapy against human prostate cancers. AB - Oncolytic viruses hold promise as "self-amplifying" cancer therapies wherein a virally killed cell can produce thousands of new viral "drugs" that can kill more cancer cells. Adenoviruses (Ads) are one family of oncolytic viruses. Most human studies have used human Ad serotype 5 (Ad5). Unfortunately, most patients are already immune to Ad5 increasing the likelihood that the agent will be neutralized if used as a cancer therapy. In this work, lower seroprevalence Ad6 was tested as a systemic therapy for prostate cancer. Ad5 and Ad6 were injected intravenously a single time in nude mice bearing human prostate tumors, and toxicity and efficacy were assessed. Ad6 was chemically shielded with polyethylene glycol (PEG) to test if this would further improve its pharmacology. Ad6 produced 30-fold lower liver damage and less toxicity than Ad5. Ad6 significantly repressed the growth of androgen-resistant human DU145 prostate tumors and androgen-sensitive LNCaP tumors after single intravenous injection. PEGylation did not change virus distribution, but blunted liver damage and cytokine production by Ad6. PEGylated Ad6 eradicated LNCaP tumors and maintained body mass, but lost potency against the more challenging DU145 tumors. These and other data suggest that low seroprevalent Ad6 has better efficacy and safety than the benchmark oncolytic virus Ad5 for systemic therapy of prostate cancer. These data also indicate that PEGylation may improve Ad6 safety, but that this shielding may reduce oncolytic efficacy after intravenous treatment. PMID- 26900600 TI - Hypothesizing Balancing Endorphinergic and Glutaminergic Systems to Treat and Prevent Relapse to Reward Deficiency Behaviors: Coupling D-Phenylalanine and N Acetyl-L-Cysteine (NAC) as a Novel Therapeutic Modality. PMID- 26900602 TI - Exploring Adult Care Experiences and Barriers to Transition in Adult Patients with Sickle Cell Disease. AB - BACKGROUND: Young adults with sickle cell anemia are at high risk for increased hospitalization and death at the time of transition to adult care. This may be related to failure of the transition system to prepare young adults for the adult healthcare system. This qualitative study was designed to identify factors related to transition that may affect the health of adults with sickle cell anemia. PROCEDURE: Ten patients currently treated in an adult hematology clinic participated in semi-structured qualitative interviews to describe their experience transitioning from pediatric to adult care and differences in adult and pediatric healthcare systems. RESULTS: Participants were generally unprepared for the adult healthcare system. Negative issues experienced by participants included physician mistrust, difficulty with employers, keeping insurance, and stress in personal relationships. Positive issues experienced by participants included improved self efficacy with improved self care and autonomy. CONCLUSIONS: In the absence of a formalized transition program, adults with sickle cell anemia experience significant barriers to adult care. In addition to medical history review and identification of an adult provider, transition programs should incorporate strategies to navigate the adult medical system, insurance and relationships as well as encouraging self efficacy. PMID- 26900601 TI - Blocking MHC class II on human endothelium mitigates acute rejection. AB - Acute allograft rejection is mediated by host CD8+ cytotoxic T lymphocytes (CTL) targeting graft class I major histocompatibility complex (MHC) molecules. In experimental rodent models, rejection requires differentiation of naive CD8+ T cells into alloreactive CTL within secondary lymphoid organs, whereas in humans, CTL may alternatively develop within the graft from circulating CD8+ effector memory T cells (TEM) that recognize class I MHC molecules on graft endothelial cells (EC). This latter pathway is poorly understood. Here, we show that host CD4+ TEM, activated by EC class II MHC molecules, provide critical help for this process. First, blocking HLA-DR on EC lining human artery grafts in immunodeficient mice reduces CD8+ CTL development within and acute rejection of the artery by adoptively transferred allogeneic human lymphocytes. Second, siRNA knockdown or CRISPR/Cas9 ablation of class II MHC molecules on EC prevents CD4+ TEM from helping CD8+ TEM to develop into CTL in vitro. Finally, implanted synthetic microvessels, formed from CRISPR/Cas9-modified EC lacking class II MHC molecules, are significantly protected from CD8+ T cell-mediated destruction in vivo. We conclude that human CD8+ TEM-mediated rejection targeting graft EC class I MHC molecules requires help from CD4+ TEM cells activated by recognition of class II MHC molecules. PMID- 26900603 TI - Preclinical Assessment of Low Doses of Cisplatin in the Management of Acute Promyelocytic Leukemia. AB - Cis-diamminedichloroplatinum (II) (cisplatin) is the most widely used chemotherapeutic drug for various cancers, but its effectiveness is limited by tumor cell resistance and the severe side effects it causes. Since high level of cisplatin is cytotoxic to both cancer and normal cells, the goal of the present study was to explore the effectiveness of prolonged low doses of cisplatin in the management of leukemia. To achieve our goal, human leukemia (HL-60) cells were treated with different doses (1, 2, or 3 uM) of cisplatin for 24, 48, 72 and 96 hours. Cell viability was assessed by MTS assay. Both oxidative stress damage and genotoxicity were estimated by antioxidants, lipid peroxidation, and comet assays, respectively. Data obtained from the MTS assay demonstrated that cisplatin treatment decreased the number of viable tumor cells by direct cell killing or by simply decreasing the rate of cellular proliferation in a dose- and time-dependent fashion. The results of the lipid peroxidation showed a significant increase (p<0.05) of malondialdehyde levels with increasing cisplatin doses. Results obtained from super oxide dismutase and catalase assays showed a gradual increase in antioxidant enzyme activity in cisplatin-treated cells compared to control cells. Data generated from the Comet assay demonstrated a significant dose-dependent increase in genotoxicity with respect to DNA damage as a result of cisplatin treatment. Taken together, our research demonstrated that cisplatin-induced cytotoxicity in HL-60 cells is mediated at least in part via induction of oxidative stress and oxidative damage. PMID- 26900604 TI - Collagen I and the fibroblast: high protein expression requires a new paradigm of post-transcriptional, feedback regulation. AB - BACKGROUND: Scaling protein production seems like a simple perturbation of transcriptional control. However, when embryonic tendon fibroblasts have to produce >50% procollagen and secrete it from the cell 4 times faster than the average protein, this taxes the cellular machinery and requires a fresh look at how the pathway is controlled. Ascorbate, a reducing agent, can stimulate procollagen production 6-fold. Procollagen mRNA levels goes up 6-fold but requires 3 days for the cell to accomplish this task. Secretion rates, the last cellular step in the process, also goes up 6-fold but this occurs in <1 h. What regulatory scheme is consistent with these properties? SCOPE OF THIS REVIEW: This review focuses on fibroblasts that make high levels of procollagen (type I) and how they regulate the collagen pathway. Data from many different labs are relevant to this problem but it is hard to see the bigger picture from a large number of small studies. This review aims to consolidate this data into a coherent model and this requires solutions to some controversies and postulating potential mechanisms where the details are still missing. MAJOR CONCLUSIONS: In high collagen producing cells, the pathway is controlled by post-transcriptional regulation. This requires feedback control between secretion and translation rates that is based on the helical structure of the procollagen molecule and additional tissue-specific modifications. GENERAL SIGNIFICANCE: Transcriptional control does not scale well to high protein production with rapid regulation. New paradigms lead to better understanding of collagen diseases and tendon morphogenesis. PMID- 26900605 TI - Pre-exposure to fine particulate matters may induce endotoxin tolerance in a mouse model. AB - Exposure to low or moderate doses of lipopolysaccharides (LPS) renders the host tolerance to a subsequent lethal dose of LPS, which is termed as endotoxin tolerance. It is characterized as the decrease in production of pro-inflammatory cytokines and the increase in production of anti-inflammatory mediators in response to a second LPS challenge. The alteration of cytokine profile protects LPS-primed hosts against a normally lethal dose of subsequent LPS challenge. Nevertheless, whether other environmental factors also trigger endotoxin tolerance remains unclear. Both epidemiologic and experimental studies have provided a link between particulate matter and human health. Here, we speculated on the effect of fine particles priming on endotoxin tolerance in a mouse model. PMID- 26900606 TI - The Relationship between Metformin and Obstructive Sleep Apnea. AB - OBJECTIVES: This study aimed to assess if metformin had any associations with the prevalence of obstructive sleep apnea in an adult type 2 diabetes population in the Midwest. HYPOTHESIS: Use of metformin is associated with decreased prevalence of obstructive sleep apnea in a adult type 2 diabetes population. METHODS: A retrospective secondary database analysis was carried out with metformin use by patients with type 2 diabetes as the primary variable of interest and obstructive sleep apnea status as the primary outcome. A sample population of 9,853 type 2 diabetes patients with one year of follow-up was used. Other variables that were analyzed included age, gender, race, hypertension, Congestive Heart Failure, Hemoglobin A1c (HbA1c), and Body Mass Index. A p-value of <0.01 was considered significant. RESULTS: Metformin usage was not significantly associated with obstructive sleep apnea prevalence (Odds Ratio: 1.17, Confidence Interval: 1.00 1.36, p = 0.049), but trended in the direction where metformin usage was associated with having obstructive sleep apnea. Lower HbA1c was found to be significantly associated with lower prevalence of obstructive sleep apnea (p <0.001). The rest of the variables followed previously published associations. CONCLUSIONS: Metformin therapy may improve sleep quality, but it may not be through methods that reduce the likelihood of developing obstructive sleep apnea. Future studies that can prove causation about this association should be considered. PMID- 26900607 TI - Identification of Infants at Risk for Autism Using Multi-parameter Hierarchical White Matter Connectomes. AB - Autism spectrum disorder (ASD) is a variety of developmental disorders that cause life-long communication and social deficits. However, ASD could only be diagnosed at children as early as 2 years of age, while early signs may emerge within the first year. White matter (WM) connectivity abnormalities have been documented in the first year of lives of ASD subjects. We introduce a novel multi-kernel support vector machine (SVM) framework to identify infants at high-risk for ASD at 6 months old, by utilizing the diffusion parameters derived from a hierarchical set of WM connectomes. Experiments show that the proposed method achieves an accuracy of 76%, in comparison to 70% with the best single connectome. The complementary information extracted from hierarchical networks enhances the classification performance, with the top discriminative connections consistent with other studies. Our framework provides essential imaging connectomic markers and contributes to the evaluation of ASD risks as early as 6 months. PMID- 26900609 TI - Hospira wins UK court case to overturn patents on Herceptin(r). PMID- 26900608 TI - Multi-view Classification for Identification of Alzheimer's Disease. AB - In this paper, we propose a multi-view learning method using Magnetic Resonance Imaging (MRI) data for Alzheimer's Disease (AD) diagnosis. Specifically, we extract both Region-Of-Interest (ROI) features and Histograms of Oriented Gradient (HOG) features from each MRI image, and then propose mapping HOG features onto the space of ROI features to make them comparable and to impose high intra-class similarity with low inter-class similarity. Finally, both mapped HOG features and original ROI features are input to the support vector machine for AD diagnosis. The purpose of mapping HOG features onto the space of ROI features is to provide complementary information so that features from different views can not only be comparable (i.e., homogeneous) but also be interpretable. For example, ROI features are robust to noise, but lack of reflecting small or subtle changes, while HOG features are diverse but less robust to noise. The proposed multi-view learning method is designed to learn the transformation between two spaces and to separate the classes under the supervision of class labels. The experimental results on the MRI images from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset show that the proposed multi-view method helps enhance disease status identification performance, outperforming both baseline methods and state-of-the-art methods. PMID- 26900610 TI - Amarin files patent infringement suit on lipid-lowering drug. PMID- 26900611 TI - Supreme Court rules against Teva in Copaxone(r) patent fight. PMID- 26900612 TI - Preface. PMID- 26900613 TI - Preface. PMID- 26900614 TI - Preface. PMID- 26900615 TI - In memoriam Jean-Marie Besson 1938 to 2014. PMID- 26900616 TI - Clinical round-up. PMID- 26900617 TI - Making productive use of the internet. PMID- 26900618 TI - Love Thy Neighbor? Ethnoracial Diversity and Trust Reexamined. AB - According to recent research, ethnoracial diversity negatively affects trust and social capital. This article challenges the current conception and measurement of "diversity" and invites scholars to rethink "so-cial capital" in complex societies. It reproduces the analysis of Putnam and shows that the association between diversity and self-reported trust is a compositional artifact attributable to residential sorting: non-whites report lower trust and are overrepresented in heterogeneous communities. The association between diversity and trust is better explained by differences between communities and their residents in terms of race/ethnicity, residential stability, and economic conditions; these classic indicators of inequality, not diversity, strongly and consistently predict self-reported trust. Diversity indexes also obscure the distinction between in-group and out-group contact. For whites, heterogeneity means more out-group neighbors; for nonwhites, heterogeneity means more in-group neighbors. Therefore, separate analyses were conducted by ethnoracial groups. Only for whites does living among out-group members--not in diverse communities per se--negatively predict trust. PMID- 26900619 TI - Abortion Liberalization in World Society, 1960-2009. AB - Controversy sets abortion apart from other issues studied by world society theorists, who consider the tendency for policies institutionalized at the global level to diffuse across very different countries. The authors conduct an event history analysis of the spread (however limited) of abortion liberalization policies from 1960 to 2009. After identifying three dominant frames (a women's rights frame, a medical frame, and a religious, natural family frame), the authors find that indicators of a scientific, medical frame show consistent association with liberalization of policies specifying acceptable grounds for abortion. Women's leadership roles have a stronger and more consistent liberalizing effect than do countries' links to a global women's rights discourse. Somewhat different patterns emerge around the likelihood of adopting an additional policy, controlling for first policy adoption. Even as support for women's autonomy has grown globally, with respect to abortion liberalization, persistent, powerful frames compete at the global level, preventing robust policy diffusion. PMID- 26900620 TI - Peer Influence, Genetic Propensity, and Binge Drinking: A Natural Experiment and a Replication. AB - The authors draw data from the College Roommate Study (ROOM) and the National Longitudinal Study of Adolescent Health to investigate gene-environment interaction effects on youth binge drinking. In ROOM, the environmental influence was measured by the precollege drinking behavior of randomly assigned roommates. Random assignment safeguards against friend selection and removes the threat of gene-environment correlation that makes gene-environment interaction effects difficult to interpret. On average, being randomly assigned a drinking peer as opposed to a nondrinking peer increased college binge drinking by 0.5-1.0 episodes per month, or 20%-40% the average amount of binge drinking. However, this peer influence was found only among youths with a medium level of genetic propensity for alcohol use; those with either a low or high genetic propensity were not influenced by peer drinking. A replication of the findings is provided in data drawn from Add Health. The study shows that gene-environment interaction analysis can uncover social-contextual effects likely to be missed by traditional sociological approaches. PMID- 26900621 TI - Droplet Microfluidic Platform for the Determination of Single-Cell Lactate Release. AB - Cancer cells release high levels of lactate that has been correlated to increased metastasis and tumor recurrence. Single-cell measurements of lactate release can identify malignant cells and help decipher metabolic cancer pathways. We present here a novel droplet microfluidic method that allows the fast and quantitative determination of lactate release in many single cells. Using passive forces, droplets encapsulated cells are positioned in an array. The single-cell lactate release rate is determined from the increase in droplet fluorescence as the lactate is enzymatically converted to a fluorescent product. The method is used to measure the cell-to-cell variance of lactate release in K562 leukemia and U87 glioblastoma cancer cell lines and under the chemical inhibition of lactate efflux. The technique can be used in the study of cancer biology, but more broadly in cell biology, to capture the full range of stochastic variations in glycolysis activity in heterogeneous cell populations in a repeatable and high throughput manner. PMID- 26900623 TI - Real-world outcome and healthcare costs of relapsed or refractory multiple myeloma: A retrospective analysis from the Chinese experience. AB - OBJECTIVES: Our aim was to retrospectively investigate the real-world outcome and healthcare costs associated with the treatment of patients with relapsed or refractory multiple myeloma (RRMM) in a Chinese single center. METHODS: A retrospective study was conducted for 93 patients between January 2008 and December 2013 in a Chinese hematology department. Total monthly costs attributable to each cost component were described across all regimens and for bortezomib-based treatment regimens. RESULTS: Mean total cost per patient-month ($1139.85) varied depending on the sequence of therapy (range: mean $51.63 $6600.96). Drugs and hospital visit were the most and the least consumed resource (65.48% and 2.87%, respectively). Mean total monthly costs were $2071.96 (range: $679.73-$6600.96) and $551.14 (range: $51.63-$1698.59) for patients receiving bortezomib and patients not receiving bortezomib, respectively. Differences between the two groups were significant for drugs; drugs costs were higher for patients treated with bortezomib. Kaplan-Meier curves showed a longer overall survival (mean [median] 31.43 [25] vs. 21.93 [18] months) for patients treated with bortezomib. CONCLUSION: Real-world costs during treatment of RRMM varied greatly. Total costs during bortezomib-based regimens are significantly higher compared with non-bortezomib regimens. Further multi-center studies are needed to assess the cost-effectiveness of bortezomib for the treatment of RRMM in China. PMID- 26900622 TI - Mechanistic Insight into Receptor-Mediated Delivery of Cationic-beta Cyclodextrin:Hyaluronic Acid-Adamantamethamidyl Host:Guest pDNA Nanoparticles to CD44(+) Cells. AB - Targeted delivery is a key element for improving the efficiency and safety of nonviral vectors for gene therapy. We have recently developed a CD44 receptor targeted, hyaluronic acid-adamantamethamidyl based pendant polymer system (HA Ad), capable of forming complexes with cationic beta-cyclodextrins (CD-PEI(+)) and pDNA. Complexes formed using these compounds (HA-Ad:CD-PEI(+):pDNA) display high water solubility, good transfection efficiency, and low cytotoxicity. Spatial and dynamic tracking of the transfection complexes by confocal microscopy and multicolor flow cytometry techniques was used to evaluate the target specificity, subcellular localization, and endosomal escape process. Our data shows that cells expressing the CD44 receptor undergo enhanced cellular uptake and transfection efficiency with HA-Ad:CD-PEI(+):pDNA complexes. This transfection system, comprised noncovalent assembly of cyclodextrin:adamantamethamidyl-modified hyaluronic acid via host:guest interactions to condense pDNA, is a potentially useful tool for targeted delivery of nucleic acid therapeutics. PMID- 26900624 TI - Rabies post-exposure prophylaxis for a child with severe allergic reaction to rabies vaccine. AB - Most adverse events (AEs) during the immunization of rabies vaccine were slight, there was little information about the allergic reaction induced by rabies vaccines and had to stop or change the immunization program. Here, we reported a case that a 4-year-old boy had category II exposure to rabies and showed severe allergic reaction after being immunized with lyophilized purified vero cell rabies vaccine (PVRV). After the anti-allergy therapy with hormone, allergy testing indicated medium allergy to egg and milk, and implied the allergic reaction most likely associated with animal-sourced gelatin in lyophilized PVRV. Therefore, a new immunization program with liquid PVRV without stabilizers under the Zegrab regimen (2-1-1) was enrolled at day 7 post-exposure. Although lower than the levels of normal <5 -year population at day 14 and 45, the neutralizing antibody (RVNA) titers of this boy showed adequate protective antibody (>= 0.5 IU/ml), even after 365 d post-immunization. This study not only highlighted the importance of several types of rabies vaccines co-existing in the market, but also implied the necessary for doctors to fully understand the allergies history of patients prior to immunize rabies vaccine. PMID- 26900625 TI - Simplified Bryostatin Analogues Protect Cells from Chikungunya Virus-Induced Cell Death. AB - Chikungunya virus (CHIKV) is a mosquito-borne alphavirus showing a recent resurgence and rapid spread worldwide. While vaccines are under development, there are currently no therapies to treat this disease, except for over-the counter (OTC) analgesics, which alleviate the devastating arthritic and arthralgic symptoms. To identify novel inhibitors of the virus, analogues of the natural product bryostatin 1, a clinical lead for the treatment of cancer, Alzheimer's disease, and HIV eradication, were investigated for in vitro antiviral activity and were found to be among the most potent inhibitors of CHIKV replication reported to date. Bryostatin-based therapeutic efforts and even recent anti-CHIKV strategies have centered on modulation of protein kinase C (PKC). Intriguingly, while the C ring of bryostatin primarily drives interactions with PKC, A- and B-ring functionality in these analogues has a significant effect on the observed cell-protective activity. Significantly, bryostatin 1 itself, a potent pan-PKC modulator, is inactive in these assays. These new findings indicate that the observed anti-CHIKV activity is not solely mediated by PKC modulation, suggesting possible as yet unidentified targets for CHIKV therapeutic intervention. The high potency and low toxicity of these bryologs make them promising new leads for the development of a CHIKV treatment. PMID- 26900630 TI - Novel Therapies for Thyroid Autoimmune Diseases. AB - C-X-C chemokine receptor (CXCR)3 and its interferon(IFN)gamma-dependent chemokines (CXCL10, CXCL9, CXCL11) are implicated in the immune-pathogenesis of autoimmune thyroiditis (AT), Graves disease (GD) and Graves Ophthalmopathy (GO). In tissue, recruited Th1 lymphocytes produce IFNgamma, enhancing the tissue secretion of IFNgamma-inducible chemokines, initiating and perpetuating the autoimmune process. Patients with AT (with hypothyroidism), and with GO and GD, particularly in the active phase, have high IFNgamma-inducible chemokines. Peroxisome proliferator-activated receptor (PPAR)gamma or -alpha agonists and methimazole exert an immune-modulation on CXCR3 chemokines in AT, GD and GO. Other studies are ongoing to evaluate new molecules acting as antagonists of CXCR3, or blocking CXCL10, in Hashimoto thyroiditis (HT), GD and GO. Recently, novel molecules targeting the various agents involved in the pathogenesis of GO, such as rituximab, have been proposed as an alternative to corticosteroids. However, randomized and controlled studies are needed to generalize these interesting results. PMID- 26900632 TI - Direct Measure of Metal-Ligand Bonding Replacing the Tolman Electronic Parameter. AB - The Tolman electronic parameter (TEP) derived from the A1-symmetrical CO stretching frequency of nickel-tricarbonyl complexes L-Ni(CO)3 with varying ligands L is misleading as (i) it is not based on a mode decoupled CO stretching frequency and (ii) a generally applicable and quantitatively correct or at least qualitatively reasonable relationship between the TEP and the metal-ligand bond strength does not exist. This is shown for a set of 181 nickel-tricarbonyl complexes using both experimental and calculated TEP values. Even the use of mode mode decoupled CO stretching frequencies (L(ocal)TEPs) does not lead to a reliable description of the metal-ligand bond strength. This is obtained by introducing a new electronic parameter that is directly based on the metal-ligand local stretching force constant. For the test set of 181 nickel complexes, a direct metal-ligand electronic parameter (MLEP) in the form of a bond strength order is derived, which reveals that phosphines and related ligands (amines, arsines, stibines, bismuthines) are bonded to Ni both by sigma-donation and pi back-donation. The strongest Ni-L bonds are identified for carbenes and cationic ligands. The new MLEP quantitatively assesses electronic and steric factors. PMID- 26900631 TI - Sericin/Dextran Injectable Hydrogel as an Optically Trackable Drug Delivery System for Malignant Melanoma Treatment. AB - Severe side effects of cancer chemotherapy prompt developing better drug delivery systems. Injectable hydrogels are an effective site-target system. For most of injectable hydrogels, once delivered in vivo, some properties including drug release and degradation, which are critical to chemotherapeutic effects and safety, are challenging to monitor. Developing a drug delivery system for effective cancer therapy with in vivo real-time noninvasive trackability is highly desired. Although fluorescence dyes are used for imaging hydrogels, the cytotoxicity limits their applications. By using sericin, a natural photoluminescent protein from silk, we successfully synthesized a hydrazone cross linked sericin/dextran injectable hydrogel. This hydrogel is biodegradable and biocompatible. It achieves efficient drug loading and controlled release of both macromolecular and small molecular drugs. Notably, sericin's photoluminescence from this hydrogel is directly and stably correlated with its degradation, enabling long-term in vivo imaging and real-time monitoring of the remaining drug. The hydrogel loaded with Doxorubicin significantly suppresses tumor growth. Together, the work demonstrates the efficacy of this drug delivery system, and the in vivo effectiveness of this sericin-based optical monitoring strategy, providing a potential approach for improving hydrogel design toward optimal efficiency and safety of chemotherapies, which may be widely applicable to other drug delivery systems. PMID- 26900633 TI - Correlated Electrochemical and Optical Detection Reveals the Chemical Reactivity of Individual Silver Nanoparticles. AB - Electrochemical (EC) impacts of single nanoparticles (NPs) on an ultramicroelectrode are coupled with optics to identify chemical processes at the level of individual NPs. While the EC signals characterize the charge transfer process, the optical monitoring gives a complementary picture of the transport and chemical transformation of the NPs. This is illustrated in the case of electrodissolution of Ag NPs. In the simplest case, the optically monitored dissolution of individual NPs is synchronized with individual EC spikes. Optics then validates in situ the concept of EC nanoimpacts for sizing and counting of NPs. Chemical complexity is introduced by using a precipitating agent, SCN(-), which tunes the overall electrodissolution kinetics. Particularly, the charge transfer and dissolution steps occur sequentially as the synchronicity between the EC and optical signals is lost. This demonstrates the level of complexity that can be revealed from such electrochemistry/optics coupling. PMID- 26900634 TI - An integrated approach for assessing the bioreceptivity of glazed tiles to phototrophic microorganisms. AB - A laboratory-based methodology was designed to assess the bioreceptivity of glazed tiles. The experimental set-up consisted of multiple steps: manufacturing of pristine and artificially aged glazed tiles, enrichment of phototrophic microorganisms, inoculation of phototrophs on glazed tiles, incubation under optimal conditions and quantification of biomass. In addition, tile intrinsic properties were assessed to determine which material properties contributed to tile bioreceptivity. Biofilm growth and biomass were appraised by digital image analysis, colorimetry and chlorophyll a analysis. SEM, micro-Raman and micro particle induced X-ray emission analyses were carried out to investigate the biodeteriorating potential of phototrophic microorganisms on the glazed tiles. This practical and multidisciplinary approach showed that the accelerated colonization conditions allowed different types of tile bioreceptivity to be distinguished and to be related to precise characteristics of the material. Aged tiles showed higher bioreceptivity than pristine tiles due to their higher capillarity and permeability. Moreover, biophysical deterioration caused by chasmoendolithic growth was observed on colonized tile surfaces. PMID- 26900636 TI - Will treatment intensification in early-stage Hodgkin lymphoma patients with a positive interim FDG-PET improve outcome? PMID- 26900635 TI - Cirrhosis is a risk factor for total hip arthroplasty for avascular necrosis. AB - Background and purpose - There are limited data on risk factors for avascular necrosis of the hip, but cirrhosis has been proposed as a risk factor. We examined the association between cirrhosis and incidence of total hip arthroplasty for avascular necrosis. Methods - We used nationwide healthcare data to identify all Danish residents diagnosed with cirrhosis in 1994-2011, and matched them 1:5 by age and sex to non-cirrhotic reference individuals from the general population. We excluded people with a previous total hip arthroplasty, a previous hip fracture, or a previous diagnosis of avascular necrosis. We used stratified Cox regression to estimate the hazard ratio (HR) for cirrhosis patients relative to reference individuals, adjusting for potential confounders. We used the cumulative incidence function to compute 5-year risks. Results - We included 25,421 cirrhosis patients and 114,052 reference individuals. Their median age was 57 years, and 65% were men. 45 cirrhosis patients and 44 reference individuals underwent total hip arthroplasty for avascular necrosis. Cirrhosis patients' HR for a total hip arthroplasty for avascular necrosis was 10 (95% CI: 6-17), yet their 5-year risk of avascular necrosis was only 0.2%. For the reference individuals, the 5-year risk was 0.02%. Interpretation - Cirrhosis is a strong risk factor for avascular necrosis of the hip, but it is rare even in cirrhosis patients. PMID- 26900637 TI - A review of trials investigating efavirenz-induced neuropsychiatric side effects and the implications. AB - Efavirenz is part of the first-line treatment for HIV patients including those in South Africa with approximately 50% experiencing neuropsychiatric side effects. A systematic review of papers reporting neuropsychiatric side effects with efavirenz published between January 2001 and December 2014 was performed, to provide guidance. 13 articles were reviewed. Patient ages ranged between 37 to 41 years, with a high percentage males. Scales used to measure incidence and severity of side effects were varied; with disease severity or stage not reported. Patients with psychoses were excluded. Most commonly reported side effects were a reduction in sleep quality, depression, dizziness and anxiety. These were generally mild and not warranting discontinuation of efavirenz. It is difficult to directly compare the studies. Standardised methods need to be introduced and all patient groups represented including the elderly, children, patients with active symptomatic illness and more women especially among the African population. PMID- 26900638 TI - Delayed graft function and chronic allograft nephropathy: diagnostic and prognostic role of neutrophil gelatinase-associated lipocalin. AB - CONTEXT: Available markers are not reliable parameters to early detect kidney injury in transplanted patients. OBJECTIVE: Examine neutrophil gelatinase associated lipocalin (NGAL) in early detection of delayed graft function (DGF) and as a long-term predictor of graft outcome. PATIENTS AND METHODS: NGAL was evaluated in 124 transplanted patients. RESULTS: Urinary NGAL levels were associated to a 10% (HR: 1.10; 95% CI: 1.04-1.25; p < 0.001) and 15% (HR: 1.15; 95% CI: 1.09-1.26; p < 0.001) increased risk of DGF and allograft nephropathy progression, respectively. CONCLUSION: NGAL reflects the entity of renal impairment in transplanted patients, representing a biomarker and an independent risk factor for DGF and chronic allograft nephropathy progression. PMID- 26900639 TI - Effects of Dosimetrically Guided I-131 Therapy on Hematopoiesis in Patients With Differentiated Thyroid Cancer. AB - OBJECTIVE: The objective of the study was to evaluate the effects of dosimetrically guided I-131 prescribed activities on hematopoiesis reflected by changes in complete blood counts (CBCs). DESIGN: This was a retrospective analysis. SETTING: The study was conducted at an academic center. PATIENTS: A total of 152 patients with differentiated thyroid cancer who had 185 dosimetrically guided I-131 treatments. INTERVENTIONS: There were no interventions. MAIN OUTCOME MEASURES: Repeated-measure ANOVA was used for the analysis of the differences in the averages of CBCs that were documented at baseline and 1, 6, 12, 24-36, and 48-60 months after I-131 treatment. RESULTS: All parameters decreased to their respective nadir at 1 month and then gradually returned toward baseline values. White blood cells (WBCs) and platelets (PLTs) were the most significantly affected cells. At 1 month, the decrease was 29.6% (P < .0001) for WBCs and 25% (P < .0001) for PLTs, whereas at 12 months, the decrease was 15.5% (P < .0001) and 13% (P < .0001), respectively. Lymphocytes appeared to be more susceptible to I-131 than neutrophils (ANCs). The decreases were small in absolute numbers for red blood cells, hematocrit and hemoglobin not surpassing 10%. Multivariate analysis demonstrated that the ratio of administered prescribed activity-to-maximum tolerated activity was associated with the decreases in WBCs (P = .0038), ANCs (P = .0063), and red blood cells (P = .029), with borderline significance for PLTs (P = .057) and hemoglobin (P = .057). CONCLUSIONS: Dosimetrically guided I-131 resulted in statistically significant decreases in CBC parameters, which were more prominent in WBCs and PLTs. Lymphocytes were more severely affected than ANCs, whereas all parameters reached a nadir at 1 month and then gradually returned toward baseline values over the 5 year follow-up of our study. PMID- 26900640 TI - Effect of Teriparatide on Bone Formation in the Human Femoral Neck. AB - PURPOSE: Teriparatide (TPTD) improves bone mass and microstructure resulting in reduced risk of vertebral and nonvertebral fractures. However, hip bone mineral density improvements are modest and there are no data confirming that TPTD reduces hip fracture risk. To study the effects of TPTD on the proximal femur, we performed a double-blind trial of TPTD vs placebo (PBO) in patients with osteoarthritis from whom femoral neck (FN) samples were obtained at total hip replacement (THR) surgery. METHODS: Participants were randomly assigned to receive TPTD or PBO for an average of 40 days before THR. Double tetracycline labeling was initiated 21 days prior to THR to allow histomorphometric assessment of bone formation. During the THR, an intact sample of the FN was procured, fixed, and sectioned transversely. Serum levels of bone turnover markers were measured at baseline and during the THR. Standard histomorphometric parameters were measured and calculated on four bone envelopes (cancellous, endocortical, intracortical, and periosteal). The primary outcome measure was bone formation rate/bone surface (BFR/BS). RESULTS: Forty individuals were enrolled (25 women, mean age, 71.5 +/- 8.0 y and 15 men, mean age, 68.9 +/- 7.7 y). In cancellous and endocortical envelopes, BFR/BS was 100% higher in the TPTD vs PBO group (P < .05). Bone turnover markers measured at the time of THR correlated with BFR/BS. CONCLUSIONS: TPTD stimulates bone formation rapidly in cancellous and endocortical envelopes of the FN. Our findings provide a mechanistic basis for TPTD-mediated improvement in FN bone mass and ultimately hip strength. This study is the first demonstration of the effect of any osteoporosis medication on osteoblast activity in the human proximal femur. PMID- 26900642 TI - Effect of Leptin Administration on Circulating Apolipoprotein CIII levels in Patients With Lipodystrophy. AB - CONTEXT: Apolipoprotein CIII (apoCIII), an inhibitor of lipoprotein lipase, plays an important role in triglyceride metabolism. However, the role of apoCIII in hypertriglyceridemia in lipodystrophy and the effects of leptin replacement on apoCIII levels are unknown. OBJECTIVE: The objective of the study was to test the hypotheses that apoCIII is elevated in hypertriglyceridemic patients with lipodystrophy and that leptin replacement in these patients lowers circulating apoCIII. DESIGN, SETTING, STUDY PARTICIPANTS, INTERVENTION, AND OUTCOME MEASURES: Using a post hoc cross-sectional case-control design, we compared serum apoCIII levels from patients with lipodystrophy not associated with HIV (n = 60) and age , gender-, race-, and ethnicity-matched controls (n = 54) participating in ongoing studies at the National Institutes of Health. In a prospective, open label, ongoing study, we studied the effects of 6-12 months of leptin replacement on apoCIII in lipodystrophy patients as an exploratory outcome. RESULTS: ApoCIII was higher in lipodystrophy patients (geometric mean [25th and 75th percentiles]) (23.9 mg/dL [14.6, 40.3]) compared with controls (14.9 mg/dL [12.3, 17.7]) (P < .0001). ApoCIII and triglyceride levels were positively correlated in patients with lipodystrophy (R = 0.72, P < .0001) and healthy controls (R = 0.6, P < .0001). Leptin replacement (6-12 mo) did not significantly alter apoCIII (before leptin: 23.4 mg/dL [14.5, 40.1]; after leptin: 21.4 mg/dL [16.7, 28.3]; P = .34). CONCLUSIONS: Leptin replacement in lipodystrophy did not alter serum apoCIII levels. Elevated apoCIII may play a role in the hypertriglyceridemia of lipodystrophy independent of leptin deficiency and replacement. PMID- 26900641 TI - Long-term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study. AB - CONTEXT: Vitamin B12 deficiency may occur with metformin treatment, but few studies have assessed risk with long-term use. OBJECTIVE: To assess the risk of B12 deficiency with metformin use in the Diabetes Prevention Program (DPP)/DPP Outcomes Study (DPPOS). DESIGN: Secondary analysis from the DPP/DPPOS. Participants were assigned to the placebo group (PLA) (n = 1082) or the metformin group (MET) (n = 1073) for 3.2 years; subjects in the metformin group received open-label metformin for an additional 9 years. SETTING: Twenty-seven study centers in the United States. PATIENTS: DPP eligibility criteria were: elevated fasting glucose, impaired glucose tolerance, and overweight/obesity. The analytic population comprised participants with available stored samples. B12 levels were assessed at 5 years (n = 857, n = 858) and 13 years (n = 756, n = 764) in PLA and MET, respectively. INTERVENTION: Metformin 850 mg twice daily vs placebo (DPP), and open-label metformin in the metformin group (DPPOS). MAIN OUTCOME MEASURES: B12 deficiency, anemia, and peripheral neuropathy. RESULTS: Low B12 (<= 203 pg/mL) occurred more often in MET than PLA at 5 years (4.3 vs 2.3%; P = .02) but not at 13 years (7.4 vs 5.4%; P = .12). Combined low and borderline-low B12 (<= 298 pg/mL) was more common in MET at 5 years (19.1 vs 9.5%; P < .01) and 13 years (20.3 vs 15.6%; P = .02). Years of metformin use were associated with increased risk of B12 deficiency (odds ratio, B12 deficiency/year metformin use, 1.13; 95% confidence interval, 1.06-1.20). Anemia prevalence was higher in MET, but did not differ by B12 status. Neuropathy prevalence was higher in MET with low B12 levels. CONCLUSIONS: Long-term use of metformin in DPPOS was associated with biochemical B12 deficiency and anemia. Routine testing of vitamin B12 levels in metformin-treated patients should be considered. PMID- 26900643 TI - Hypothyroidism Following Hemithyroidectomy: Incidence, Risk Factors, and Clinical Characteristics. AB - We conducted a retrospective cohort study involving 405 patients to evaluate characteristics of hypothyroidism following hemithyroidectomy, suggesting an appropriate follow-up strategy after thyroid-conserving surgery. PMID- 26900644 TI - First-Principles United Atom Force Field for the Ionic Liquid BMIM(+)BF4(-): An Alternative to Charge Scaling. AB - Molecular dynamics study of ionic liquids (ILs) is a challenging task. While accurate fully polarizable atomistic models exist, they are computationally too demanding for routine use. Most nonpolarizable atomistic models predict diffusion constants that are much lower than experiment. Scaled charge atomistic models are cost-effective and give good results for single component ILs but are in qualitative error for the phase behavior of mixtures, due to inaccurate prediction of the IL cohesive energy. In this work, we present an alternative approach for developing computationally efficient models that importantly preserves both the correct dynamics and cohesive energy of the IL. Employing a "top-down" approach, a hierarchy of coarse-grained models for BMIM(+)BF4(-) are developed by systematically varying the polarization/atomic resolution of the distinct functional groups. Parametrization is based on symmetry-adapted perturbation theory (SAPT) calculations involving the homomolecular species; all cross interactions are obtained from mixing rules, and there are no adjustable parameters. We find that enhanced dynamics from a united-atom description counteracts the effect of reduced polarization, enabling computationally efficient models that exhibit quantitative agreement with experiment for both static and dynamic properties. We give explicit suggestions for reduced description models that are computationally more efficient, more accurate, and more fundamentally sound than existing nonpolarizable atomistic models. PMID- 26900645 TI - Manifestations of Torsion-CH Stretch Coupling in the Infrared Spectrum of CH3OO. AB - With a step-scan Fourier-transform spectrometer we recorded temporally resolved infrared absorption spectra of CH3OO radicals that were produced upon irradiation of CH3COCH3 and O2 at 193 nm in a flowing mixture. At a resolution of 0.15 cm( 1), the rotational structure of the nu2 band of CH3OO near 2954.4 cm(-1) is partially resolved and shows an unexpectedly broadened, and somewhat distorted, Q branch. A 4D model Hamiltonian, consisting of three CH stretches and the methyl torsion, was developed to explore the origins of this broadening. The vibrational progressions predicted by the model Hamiltonian and the rotational contours of the nu2 band, based on experimental ground-state rotational parameters and their values scaled by their calculated ratios for the upper state, produced simulations in satisfactory agreement with the observed spectrum. These results provide new insight into the vibrational couplings in CH3OO. PMID- 26900647 TI - Copper-Catalyzed Diastereoselective Addition of Diborylmethane to N-tert Butanesulfinyl Aldimines: Synthesis of beta-Aminoboronates. AB - We have developed a highly chemo- and diastereoselective alkylation of N-tert butanesulfinyl aldimines with diborylmethane. Whereas the addition of diborylmethane under metal-free conditions shows poor diastereoselectivity, the use of a copper catalyst and a bidentate phosphine ligand significantly enhances the diastereoselectivity, providing chiral beta-aminoboronates in good yields. On the basis of the stereochemical outcome, we propose that the reaction likely proceeds via a boron-chelating six-membered chairlike transition state. PMID- 26900646 TI - Vaccine criticism on the Internet: Propositions for future research. AB - Research on vaccine criticism on the Internet is now at a crossroads, with an already important body of knowledge published on the subject but also a continuous and even growing interest in the scientific community. In this commentary, we reflect on the published literature from the standpoint of sociologists interested in social movements and their activists and the influence they can have on vaccination behaviors. We suggest several avenues of research for future studies of vaccine criticism on the Internet: 1) paying more attention to the actors who publish vaccine critical contents and to their use of the Internet in relationship to the other means through which they try to mobilize the population - the production of vaccine critical information on the Internet, and not only its nature and its reception, should therefore become one of the main objects of this strand of research -; 2) paying closer attention to what distinguishes the different strands of vaccine criticism regarding both what they dislike about vaccines (or about a given vaccine) and how this fight is integrated in a more general political or cultural struggle; 3) investigating further how the new forms of social interactions allowed by the Internet affect the transmission of vaccine related information and the capacity of vaccine critical actors to enroll members of the public in their political or cultural struggle. PMID- 26900648 TI - Genes involved in Listeria monocytogenes biofilm formation at a simulated food processing plant temperature of 15 degrees C. AB - Listeria monocytogenes is a pathogenic foodborne bacterium whose persistence in food processing environments is in part attributed to its biofilm formation. Most biofilm studies have been carried out at 30-37 degrees C rather than at temperatures found in the food processing plants (i.e., 10-20 degrees C). The objective of the present study was to mine for novel genes that contribute to L. monocytogenes biofilm formation at 15 degrees C using the random insertional mutagenesis approach. A library of 11,024 L. monocytogenes 568 (serotype 1/2a) Himar1 insertional mutants was created. Mutants with reduced or enhanced biofilm formation at 15 degrees C were detected in microtiter plate assays with crystal violet and safranin staining. Fourteen mutants expressed enhanced biofilm phenotypes, and harbored transposon insertions in genes encoding cell wall biosynthesis, motility, metabolism, stress response, and cell surface associated proteins. Deficient mutants (n=5) contained interruptions in genes related to peptidoglycan, teichoic acid, or lipoproteins. Enhanced mutants produced significantly (p<0.05) higher cell densities in biofilm formed on stainless steel (SS) coupons at 15 degrees C (48 h) than deficient mutants, which were also more sensitive to benzalkonium chloride. All biofilm deficient mutants and four enhanced mutants in the microtiter plate assay (flaA, cheR, lmo2563 and lmo2488) formed no biofilm in a peg lid assay (Calgary biofilm device) while insertions in lmo1224 and lmo0543 led to excess biofilm in all assays. Two enhanced biofilm formers were more resistant to enzymatic removal with DNase, proteinase K or pectinase than the parent strain. Scanning electron microscopy of individual biofilms made by five mutants and the parent on SS surfaces showed formation of heterogeneous biofilm with dense zones by immotile mutants, while deficient mutants exhibited sparse growth. In conclusion, interruptions of 9 genes not previously linked to biofilm formation in L. monocytogenes (lmo2572, lmo2488 (uvrA), lmo1224, lmo0434 (inlB), lmo0263 (inlH), lmo0543, lmo0057 (EsaA), lmo2563, lmo0453), caused enhanced biofilm formation in the bacterium at 15 degrees C. The remaining mutants harbored interruptions in 10 genetic loci previously associated with biofilm formation at higher temperatures, indicating some temperature driven differences in the formation of biofilm by L. monocytogenes. PMID- 26900650 TI - Cognitive deterioration in adult epilepsy: Does accelerated cognitive ageing exist? AB - A long-standing concern has been whether epilepsy contributes to cognitive decline or so-called 'epileptic dementia'. Although global cognitive decline is generally reported in the context of chronic refractory epilepsy, it is largely unknown what percentage of patients is at risk for decline. This review is focused on the identification of risk factors and characterization of aberrant cognitive trajectories in epilepsy. Evidence is found that the cognitive trajectory of patients with epilepsy over time differs from processes of cognitive ageing in healthy people, especially in adulthood-onset epilepsy. Cognitive deterioration in these patients seems to develop in a 'second hit model' and occurs when epilepsy hits on a brain that is already vulnerable or vice versa when comorbid problems develop in a person with epilepsy. Processes of ageing may be accelerated due to loss of brain plasticity and cognitive reserve capacity for which we coin the term 'accelerated cognitive ageing'. We believe that the concept of accelerated cognitive ageing can be helpful in providing a framework understanding global cognitive deterioration in epilepsy. PMID- 26900649 TI - The hairpin region of Ndc80 is important for the kinetochore recruitment of Mph1/MPS1 in fission yeast. AB - The establishment of proper kinetochore-microtubule attachments facilitates faithful chromosome segregation. Incorrect attachments activate the spindle assembly checkpoint (SAC), which blocks anaphase onset via recruitment of a cohort of SAC components (Mph1/MPS1, Mad1, Mad2, Mad3/BubR1, Bub1 and Bub3) to kinetochores. KNL1, a component of the outer kinetochore KMN network (KNL1/Mis12 complex/Ndc80 complex), acts as a platform for Bub1 and Bub3 localization upon its phosphorylation by Mph1/MPS1. The Ndc80 protein, a major microtubule-binding site, is critical for MPS1 localization to the kinetochores in mammalian cells. Here we characterized the newly isolated mutant ndc80-AK01 in fission yeast, which contains a single point mutation within the hairpin region. This hairpin connects the preceding calponin-homology domain with the coiled-coil region. ndc80-AK01 was hypersensitive to microtubule depolymerizing reagents with no apparent growth defects without drugs. Subsequent analyses indicated that ndc80 AK01 is defective in SAC signaling, as mutant cells proceeded into lethal cell division in the absence of microtubules. Under mitotic arrest conditions, all SAC components (Ark1/Aurora B, Mph1, Bub1, Bub3, Mad3, Mad2 and Mad1) did not localize to the kinetochore. Further genetic analyses indicated that the Ndc80 hairpin region might act as a platform for the kinetochore recruitment of Mph1, which is one of the most upstream SAC components in the hierarchy. Intriguingly, artificial tethering of Mph1 to the kinetochore fully restored checkpoint signaling in ndc80-AK01 cells, further substantiating the notion that Ndc80 is a kinetochore platform for Mph1. The hairpin region of Ndc80, therefore, plays a critical role in kinetochore recruitment of Mph1. PMID- 26900651 TI - A systematic review of the relationship between eating, weight and inhibitory control using the stop signal task. AB - Altered inhibitory control (response inhibition, reward-based inhibition, cognitive inhibition, reversal learning) has been implicated in eating disorders (EDs) and obesity. It is unclear, however, how different types of inhibitory control contribute to eating and weight-control behaviours. This review evaluates the relationship between one aspect of inhibitory control (a reactive component of motor response inhibition measured by the stop signal task) and eating/weight in clinical and non-clinical populations. Sixty-two studies from 58 journal articles were included. Restrained eaters had diminished reactive inhibitory control compared to unrestrained eaters, and showed greatest benefit to their eating behaviour from manipulations of inhibitory control. Obese individuals may show less reactive inhibitory control but only in the context of food-specific inhibition or after executive resources are depleted. Of the limited studies in EDs, the majority found no impairment in reactive inhibitory control, although findings are inconsistent. Thus, altered reactive inhibitory control is related to some maladaptive eating behaviours, and hence may provide a therapeutic target for behavioural manipulations and/or neuromodulation. However, other types of inhibitory control may also contribute. Methodological and theoretical considerations are discussed. PMID- 26900652 TI - The 2015 Pregnancy Summit, London, UK. AB - Pregnancy Summit, Cineworld, The O2, London, UK, 29 September to 1 October 2015 The 2015 Pregnancy Summit was held over 3 days from 29 September to 1 October at Cineworld, The O2, London, UK. The event brings together a multidisciplinary faculty of international researchers and clinicians to discuss both scientific and clinical aspects of pregnancy-related issues in an informal setting. The goal of the meeting was to provide delegates with an update of recent advances in management of pregnancy-related conditions, to present research data and to discuss the current attitudes and practices in relevant topics. An extensive range of topics were discussed, from preeclampsia and treatment of hypertension, to the psychological impact of termination of pregnancy and feticide. This report will summarize a selection of the lectures presented. PMID- 26900653 TI - Weight Gain Alters Adiponectin Receptor 1 Expression on Adipose Tissue-Resident Helios+ Regulatory T Cells. AB - Adipose tissue produces multiple mediators that modulate the immune response. Adiponectin is an adipocyte-derived cytokine that exhibits metabolic and anti inflammatory effects. Adiponectin acts through binding to adiponectin receptor 1 and 2 (AdipoR1/AdipoR2). AdipoR1 is ubiquitously expressed, whereas AdipoR2 is restricted to skeletal muscle and liver. AdipoR1 expression has been reported on a small percentage of T cells; nevertheless, it is still unknown whether Foxp3(+) regulatory T cells (Tregs) express AdipoR1. Recently, it has been shown that Tregs accumulate in adipose tissue and that they play a potential role in modulating adipose tissue inflammation. Our aim was to evaluate AdipoR1 expression in adipose tissue-resident Tregs and to evaluate the effect of weight gain on this expression. Male C57BL/6 mice were fed with a high-fat diet for 14 weeks (to develop overweight) or 21 weeks (to develop obesity). Mice on a standard diet were used as age-matched controls. Helios expression was evaluated as a marker to discriminate thymic-derived from peripherally induced Tregs. The majority of Tregs in both adipose tissue and the spleen expressed Helios. Adipose tissue Tregs expressed higher levels of AdipoR1 than Tregs in the spleen. AdipoR1 expression on adipose tissue Helios(+) Tregs was negatively correlated with epididymal fat. Overall, we show that AdipoR1 is expressed on adipose tissue resident Tregs, mainly Helios(+) Tregs, and that this expression is dependent on weight and fat accumulation. Because both adiponectin and Tregs play roles in anti-inflammatory mechanisms, our data propose a new mechanism through which weight gain might alter immunoregulation. PMID- 26900654 TI - Are the Responses to Resistance Training Different Between the Preferred and Nonpreferred Limbs? AB - Humans preferentially recruit limbs to functionally perform a range of daily tasks, which may lead to performance asymmetries. Because initial training status plays an important role in the rate of progression during resistance training, could asymmetries between the preferred and nonpreferred limbs lead to different magnitudes of strengthening during a resistance training program? This issue motivated this study, in which 12 healthy and physically active men completed a 4 week control period followed by a 12-week isokinetic resistance training program, performed twice a week, including 3-5 sets of 10 maximal eccentric contractions for each limb. Every 4 weeks, knee extensor peak torques at concentric, isometric, and eccentric tests were measured using an isokinetic dynamometer and the sum of quadriceps muscle thickness was determined by ultrasound images. Before training, concentric peak torque was similar between limbs but isometric and eccentric peak torques were significantly smaller in the nonpreferred compared with the preferred limb (4.9 and 5.8%, respectively). Bilateral strength symmetry remained constant throughout the training period for concentric tests. For eccentric and isometric tests, symmetry was reached at the fourth and eighth training weeks, respectively. After 12 weeks, between-limb percent nonsignificant differences were -0.62% for isometric and -1.93% for eccentric tests. The sum of knee extensor muscle thickness had similar values before training and presented similar changes throughout the study for both the preferred and the nonpreferred limbs. In conclusion, the nonpreferred limb presents higher strength gain than the preferred limb at the initial phase of an isokinetic resistance training program, and this increased strength gain is not associated with muscle hypertrophy. PMID- 26900655 TI - Discovery of novel heteroarylmethylcarbamodithioates as potent anticancer agents: Synthesis, structure-activity relationship analysis and biological evaluation. AB - A series of new analogs based on the structure of lead compound 10 were designed, synthesized and evaluated for their in vitro anti-cancer activities against four selected human cancer cell lines (HL-60, Bel-7402, SK-BR-3 and MDA-MB-468). Several synthesized compounds exhibited improved anti-cancer activities comparing with lead compound 10. Among them, 1,3,4-oxadiazole analogs 17o showed highest bioactivity with IC50 values of 1.23, 0.58 and 4.29 MUM against Bel-7402, SK-BR-3 and MDA-MB-468 cells, respectively. It is noteworthy that 17o has potent anti proliferation activity toward a panel of cancer cells with relatively less cytotoxicity to nonmalignant cells. The further mechanistic study showed that it induced apoptosis and cell cycle arrest through disrupting spindle assembly in mitotic progression, indicating these synthesized dithiocarbamates represented a novel series of anti-cancer compounds targeting mitosis. PMID- 26900656 TI - Dihydropyrazole derivatives as telomerase inhibitors: Structure-based design, synthesis, SAR and anticancer evaluation in vitro and in vivo. AB - It is of our interest to generate and identify novel compounds with regulation telomerase for cancer therapy. In order to carry out more rational design, based on structure-based drug design, several series of N-substituted-dihydropyrazole derivatives, totally 78 compounds as potential human telomerase inhibitors were designed and synthesized. The results demonstrated that some compounds had potent anticancer activity against four tumor cell lines, and showed good selectivity on tumor cells over somatic cells. By the modified TRAP assay, compound 13i exhibited the most potent inhibitory activity against telomerase with an IC50 value of 0.98 MUM. In vivo evaluation results indicated that compound 13i could inhibit growth of S180 and HepG2 tumor-bearing mice, and it also significantly enhanced the survival rate of EAC tumor-bearing mice. The further results in vivo confirmed that it could significantly improve pathological changes of N,N diethylnitrosamine (DEN)-induced rat hepatic tumor. These data support further studies to assess rational design of more efficient telomerase inhibitors in the future. PMID- 26900657 TI - New direct inhibitors of InhA with antimycobacterial activity based on a tetrahydropyran scaffold. AB - Tetrahydropyran derivative 1 was discovered in a high-throughput screening campaign to find new inhibitors of mycobacterial InhA. Following initial in-vitro profiling, a structure-activity relationship study was initiated and a focused library of analogs was synthesized and evaluated. This yielded compound 42 with improved antimycobacterial activity and low cytotoxicity. Additionally, the crystal structure of InhA in complex with inhibitor 1 was resolved, to reveal the binding mode and provide hints for further optimization. PMID- 26900658 TI - Rational design in search for 5-phenylhydantoin selective 5-HT7R antagonists. Molecular modeling, synthesis and biological evaluation. AB - A series of novel arylpiperazine 5-(4-fluorophenyl)-5-methylhydantoins with 2 hydroxypropyl linker (2-15) was synthesized and evaluated on their affinity towards serotonin 5-HT7 receptor (5-HT7R) in comparison to other closely related GPCRs: serotonin 5-HT1A, and dopamine D2 receptors. The functional activity studied through the measurement of 5-HT7R-mediated cyclic AMP production in Human Embryonic Kidney 293 cells (HEK293) stably expressing human 5-HT7 proved their antagonistic properties. The lead structure was also examined in the preliminary metabolic stability study using human liver microsomes (HMLs). The process of selection of candidates for synthesis was supported by a special molecular modeling workflow including combinatorial library generation, docking, and machine learning-based assessment. Additionally, in silico predictions of selectivity over 5-HT1AR and D2R, as well as functional activity were carried out. The newly synthesized compounds were proved to possess a potent affinity for 5-HT7R, similar to that of the lead structure of 5-(4-fluorophenyl)-3-(3-(4-(2 methoxyphenyl)piperazin-1-yl)-2-hydroxypropyl)-5-methylimidazolidine-2,4-dione (1). For several derivatives, significant selectivity both over 5-HT1AR and D2R was found. PMID- 26900659 TI - Novel morpholinoquinoline nucleus clubbed with pyrazoline scaffolds: Synthesis, antibacterial, antitubercular and antimalarial activities. AB - A series of novel morpholinoquinoline based conjugates with pyrazoline moiety were synthesized under microwave irradiation. The newly synthesized compounds were screened for their preliminary in vitro antibacterial activity against a panel of pathogenic strains of bacteria and fungi, antituberculosis activity against Mycobacterium tuberculosis H37Rv and antimalarial activity against Plasmodium falciparum. Most of them exhibited significant antibacterial activity as compared to the first line drugs. Compounds 6a and 9d were found to possess excellent antibacterial activity potency as compared to ampicillin (286 MUM), chloramphenicol (154 MUM) and ciprofloxacin (150 MUM). In antifungal screening, against Candida albicans, compounds 6c, 7c, 8a, 8b, 8c and 9b showed significant activity as compared to griseofulvin (1147 MUM). Compounds 8b, 6b, 9d, 6a, 9b, 7b and 8a displayed brilliant activity against P. falciparum strain as compared to chloroquine (IC50 0.062 MUM) as well as quinine (IC50 0.826 MUM). Compounds 6d, 7b, 8b, 9c and 9d exhibited superior antitubercular activity. Among them 8b was found to be equipotent to rifampicin with 95% inhibition. The cytotoxicity of the synthesized compounds was tested using bioassay of Schizosaccharomyces pombe cells at cellular level. PMID- 26900660 TI - Design, synthesis, and structure-activity relationship study of glycyrrhetinic acid derivatives as potent and selective inhibitors against human carboxylesterase 2. AB - Human carboxylesterase 2 (hCE2), one of the major carboxylesterases in the human intestine and various tumour tissues, plays important roles in the oral bioavailability and treatment outcomes of ester- or amide-containing drugs or prodrugs, such as anticancer agents CPT-11 (irinotecan) and LY2334737 (gemcitabine). In this study, 18beta-glycyrrhetinic acid (GA), the most abundant pentacyclic triterpenoid from natural source, was selected as a reference compound for the development of potent and specific inhibitors against hCE2. Simple semi-synthetic modulation on GA was performed to obtain a series of GA derivatives. Structure-activity relationship analysis brought novel insights into the structure modification of GA. Converting the 11-oxo-12-ene of GA to 12-diene moiety, and C-3 hydroxyl and C-30 carboxyl group to 3-O-beta-carboxypropionyl and ethyl ester respectively, led to a significant enhancement of the inhibitory effect on hCE2 and the selectivity over hCE1. These exciting findings inspired us to design and synthesize the more potent compound 15 (IC50 0.02 MUM) as a novel and highly selective inhibitor against hCE2, which was 3463-fold more potent than the parent compound GA and demonstrated excellent selectivity (>1000-fold over hCE1). The molecular docking study of compound 15 and the active site of hCE1 and hCE2 demonstrated that the potent and selective inhibition of compound 15 toward hCE2 could partially be attributed to its relatively stronger interactions with hCE2 than with hCE1. PMID- 26900662 TI - Transcriptome-scale RNase-footprinting of RNA-protein complexes. AB - Ribosome profiling is widely used to study translation in vivo, but not all sequence reads correspond to ribosome-protected RNA. Here we describe Rfoot, a computational pipeline that analyzes ribosomal profiling data and identifies native, nonribosomal RNA-protein complexes. We use Rfoot to precisely map RNase protected regions within small nucleolar RNAs, spliceosomal RNAs, microRNAs, tRNAs, long noncoding (lnc)RNAs and 3' untranslated regions of mRNAs in human cells. We show that RNAs of the same class can show differential complex association. Although only a subset of lncRNAs show RNase footprints, many of these have multiple footprints, and the protected regions are evolutionarily conserved, suggestive of biological functions. PMID- 26900664 TI - Inclusion of Strep-tag II in design of antigen receptors for T-cell immunotherapy. AB - Adoptive immunotherapy with genetically engineered T cells has the potential to treat cancer and other diseases. The introduction of Strep-tag II sequences into specific sites in synthetic chimeric antigen receptors or natural T-cell receptors of diverse specificities provides engineered T cells with a marker for identification and rapid purification, a method for tailoring spacer length of chimeric receptors for optimal function, and a functional element for selective antibody-coated, microbead-driven, large-scale expansion. These receptor designs facilitate cGMP manufacturing of pure populations of engineered T cells for adoptive T-cell therapies and enable in vivo tracking and retrieval of transferred cells for downstream research applications. PMID- 26900666 TI - Geometric effects in the electronic transport of deformed nanotubes. AB - Quasi-two-dimensional systems may exibit curvature, which adds three-dimensional influence to their internal properties. As shown by da Costa (1981 Phys. Rev. A 23 1982-7), charged particles moving on a curved surface experience a curvature dependent potential which greatly influence their dynamics. In this paper, we study the electronic ballistic transport in deformed nanotubes. The one-electron Schrodinger equation with open boundary conditions is solved numerically with a flexible MAPLE code made available as supplementary data. We find that the curvature of the deformations indeed has strong effects on the electron dynamics, suggesting its use in the design of nanotube-based electronic devices. PMID- 26900665 TI - Timing of adjuvant chemotherapy in colorectal cancer. AB - AIM: Delay in commencing adjuvant therapy for colorectal cancer seems to impair survival in some retrospective studies. This study was planned to evaluate its impact on survival. METHODS: This was a retrospective study enrolling patients registered from 2000 to 2012 in two large cancer-dedicated institutions in Brazil. The primary outcome was overall survival according to early vs late chemotherapy initiation. The interval between the primary surgery and the start of adjuvant chemotherapy was calculated. Survival was estimated using the Kaplan Meier method and the impact of multiple prognostic factors on survival by Cox regression analysis. RESULTS: By the end of 2012, a total of 1963 Stage II and III colorectal patients were identified and 1318 patients received adjuvant chemotherapy, with 22% and 46% of those starting adjuvant chemotherapy within 6 weeks and 8 weeks of surgery. The median period of follow-up was 41 months. Patients starting chemotherapy within 6-8 weeks of surgery had longer overall survival compared with those who started after (6 weeks vs later, hazard ratio 0.76, 95% CI 0.57-0.99, P = 0.046; 8 weeks vs later, hazard ratio 0.74, 95% CI 0.59-0.93, P = 0.011). In the multivariate analysis, age, stage, histological grade, angiolymphatic invasion, emergency surgery and preoperative therapy were independent prognostic factors, but the interval between surgery and start of adjuvant therapy was not. CONCLUSION: In this large retrospective study, the standard prognostic factors impacted on survival whereas the timing of adjuvant therapy did not. Patients with delayed adjuvant chemotherapy may have worse prognostic factors which could play a major role in their poor outcome. PMID- 26900663 TI - Directed evolution of a recombinase that excises the provirus of most HIV-1 primary isolates with high specificity. AB - Current combination antiretroviral therapies (cART) efficiently suppress HIV-1 reproduction in humans, but the virus persists as integrated proviral reservoirs in small numbers of cells. To generate an antiviral agent capable of eradicating the provirus from infected cells, we employed 145 cycles of substrate-linked directed evolution to evolve a recombinase (Brec1) that site-specifically recognizes a 34-bp sequence present in the long terminal repeats (LTRs) of the majority of the clinically relevant HIV-1 strains and subtypes. Brec1 efficiently, precisely and safely removes the integrated provirus from infected cells and is efficacious on clinical HIV-1 isolates in vitro and in vivo, including in mice humanized with patient-derived cells. Our data suggest that Brec1 has potential for clinical application as a curative HIV-1 therapy. PMID- 26900667 TI - Two Case Reports on Use of Prazosin for Drug Dreams. AB - Substance abuse and dependence is estimated to cost roughly $700 billion annually including direct and indirect care in the United States. Drug dreams (DD), or using dreams, are a reportedly common phenomenon among patients with substance abuse, and have been postulated as triggers for relapse. Prazosin is an alpha-1 receptor antagonist originally approved by the United States Food and Drug Administration for the treatment of hypertension. Prazosin passes the blood brain barrier easily, contributing to central and cognitive effects. Prazosin's efficacy has been demonstrated in the management of posttraumatic stress disorder (PTSD), and associated nightmares. We present the cases of two patients with substance use disorder experiencing DD which resolved after the addition of prazosin during an acute psychiatric hospitalization. To our knowledge, this is the first time treatment of DD with prazosin has been reported in the literature. Both patients reported an alleviation of their DD after the medication was initiated. The effect was immediate and results were seen on the same night of the initial dose. The precise mechanism of this effect is unclear, but we hypothesize it is related to the decrease in noradrenaline effects at alpha-1 adrenoreceptors in the brain, similar to the effect on nightmares in PTSD. The key limitation is the low number of patients and lack of follow up presented in this report. No causal relationship can be established between the use of prazosin and resolution of DD in our patients. PMID- 26900668 TI - Tobacco Use Disorder: A Family Disease. AB - This clinical case presentation discusses a family in which 3 generations are affected by tobacco. The discussants discuss approaches to be taken to minimize the exposure of an infant to tobacco smoke from older relatives, behavioral and pharmacological approaches to assist smoking cessation, and concerns regarding electronic cigarettes. PMID- 26900669 TI - Using a Learning Collaborative Strategy With Office-based Practices to Increase Access and Improve Quality of Care for Patients With Opioid Use Disorders. AB - OBJECTIVES: Rapidly escalating rates of heroin and prescription opioid use have been widely observed in rural areas across the United States. Although US Food and Drug Administration-approved medications for opioid use disorders exist, they are not routinely accessible to patients. One medication, buprenorphine, can be prescribed by waivered physicians in office-based practice settings, but practice patterns vary widely. This study explored the use of a learning collaborative method to improve the provision of buprenorphine in the state of Vermont. METHODS: We initiated a learning collaborative with 4 cohorts of physician practices (28 total practices). The learning collaborative consisted of a series of 4 face-to-face and 5 teleconference sessions over 9 months. Practices collected and reported on 8 quality-improvement data measures, which included the number of patients prescribed buprenorphine, and the percent of unstable patients seen weekly. Changes from baseline to 8 months were examined using a p-chart and logistic regression methodology. RESULTS: Physician engagement in the learning collaborative was favorable across all 4 cohorts (85.7%). On 6 of the 7 quality improvement measures, there were improvements from baseline to 8 months. On 4 measures, these improvements were statistically significant (P < 0.001). Importantly, practice variation decreased over time on all measures. The number of patients receiving medication increased only slightly (3.4%). CONCLUSIONS: Results support the effectiveness of a learning collaborative approach to engage physicians, modestly improve patient access, and significantly reduce practice variation. The strategy is potentially generalizable to other systems and regions struggling with this important public health problem. PMID- 26900670 TI - Platinum(IV) prodrug conjugated Pd@Au nanoplates for chemotherapy and photothermal therapy. AB - Owing to the excellent near infrared (NIR) light absorption and efficient passive targeting toward tumor tissue, two-dimensional (2D) core-shell PEGylated Pd@Au nanoplates have great potential in both photothermal therapy and drug delivery systems. In this work, we successfully conjugate Pd@Au nanoplates with a platinum(IV) prodrug c,c,t-[Pt(NH3)2Cl2(O2CCH2CH2CO2H)2] to obtain a nanocomposite (Pd@Au-PEG-Pt) for combined photothermal-chemotherapy. The prepared Pd@Au-PEG-Pt nanocomposite showed excellent stability in physiological solutions and efficient Pt(IV) prodrug loading. Once injected into biological tissue, the Pt(IV) prodrug was easily reduced by physiological reductants (e.g. ascorbic acid or glutathione) into its cytotoxic and hydrophilic Pt(II) form and released from the original nanocomposite, and the NIR laser irradiation could accelerate the release of Pt(II) species. More importantly, Pd@Au-PEG-Pt has high tumor accumulation (29%ID per g), which makes excellent therapeutic efficiency at relatively low power density possible. The in vivo results suggested that, compared with single therapy the combined thermo-chemotherapy treatment with Pd@Au-PEG-Pt resulted in complete destruction of the tumor tissue without recurrence, while chemotherapy using Pd@Au-PEG-Pt without irradiation or photothermal treatment using Pd@Au-PEG alone did not. Our work highlights the prospects of a feasible drug delivery strategy of the Pt prodrug by using 2D Pd@Au nanoplates as drug delivery carriers for multimode cancer treatment. PMID- 26900671 TI - Bimetallic Metal-Organic Frameworks: Probing the Lewis Acid Site for CO2 Conversion. AB - A highly porous metal-organic framework (MOF) incorporating two kinds of second building units (SBUs), i.e., dimeric paddlewheel (Zn2 (COO)4 ) and tetrameric (Zn4 (O)(CO2 )6 ), is successfully assembled by the reaction of a tricarboxylate ligand with Zn(II) ion. Subsequently, single-crystal-to-single-crystal metal cation exchange using the constructed MOF is investigated, and the results show that Cu(II) and Co(II) ions can selectively be introduced into the MOF without compromising the crystallinity of the pristine framework. This metal cation exchangeable MOF provides a useful platform for studying the metal effect on both gas adsorption and catalytic activity of the resulted MOFs. While the gas adsorption experiments reveal that Cu(II) and Co(II) exchanged samples exhibit comparable CO2 adsorption capability to the pristine Zn(II) -based MOF under the same conditions, catalytic investigations for the cycloaddition reaction of CO2 with epoxides into related carbonates demonstrate that Zn(II) -based MOF affords the highest catalytic activity as compared with Cu(II) and Co(II) exchanged ones. Molecular dynamic simulations are carried out to further confirm the catalytic performance of these constructed MOFs on chemical fixation of CO2 to carbonates. This research sheds light on how metal exchange can influence intrinsic properties of MOFs. PMID- 26900673 TI - Prevalence, Distribution, and Development of an Ecological Niche Model of Dermacentor variabilis Ticks Positive for Rickettsia montanensis. AB - Rickettsia montanensis has long been considered a nonpathogenic member of the spotted fever group rickettsiae. However, the infection potential of R. montanensis is being revisited in light of its recent association with a case of human infection in the United States and the possibility that additional cases may have been misdiagnosed as Rocky Mountain spotted fever. To this end, DNA was extracted from American dog ticks (Dermacentor variabilis) removed from Department of Defense (DoD) personnel and their dependents at DoD medical treatment facilities (MTFs) during 2002-2012 (n = 4792). These 4792 samples were analyzed for the presence of R. montanensis (n = 36; 2.84%) and all vector DNA was confirmed to be of D. variabilis origin using a novel Dermacentor genus specific quantitative real-time polymerase chain reaction procedure, Derm, and a novel Dermacentor species multilocus sequence typing assay. To assess the risk of R. montanensis infection, the positive and negative samples were geographically mapped utilizing MTF site locations. Tick localities were imported into a geographical information systems (GIS) program, ArcGIS, for mapping and analysis. The ecological niche modeling (ENM) program, Maxent, was used to estimate the probability of tick presence in eastern United States using locations of both R. montanensis-positive and -negative ticks, climate, and elevation data. The ENM for R. montanensis-positive D. variabilis estimated high probabilities of the positive ticks occurring in two main areas, including the northern Midwest and mid-Atlantic portions of the northeastern regions of United States, whereas the R. montanensis-negative D. variabilis tick model showed a wider estimated range. The results suggest that R. montanensis-positive and -negative D. variabilis have different ranges where humans may be at risk and are influenced by similar and different factors. PMID- 26900674 TI - SCAPIS Pilot Study: Sitness, Fitness and Fatness - Is Sedentary Time Substitution by Physical Activity Equally Important for Everyone's Markers of Glucose Regulation? AB - BACKGROUND: Although moderate-to-vigorous physical activity (MVPA) is mainly recommended for glucose control, light physical activity (LIPA) may also have the potential to induce favorable changes. We investigated sedentary time (SED) substitution with equal time in LIPA and MVPA, and the association with markers of glucose regulation and insulin sensitivity after stratification by waist circumference, fitness and fasting glucose levels. METHODS: A total of 654 men and women, 50 to 64 years, from the SCAPIS pilot study were included. Daily SED, LIPA and MVPA were assessed using hip-worn accelerometers. Fasting plasma glucose, insulin and HOMA-IR were determined. RESULTS: Substituting 30 min of SED with LIPA was significantly associated with 3.0% lower fasting insulin values and 3.1% lower HOMA-IR values, with even lower levels when substituting SED with MVPA. Participants with lower fitness and participants with high fasting glucose levels benefited significantly more from substituting 30 min of SED with LIPA compared with participants with normal to high fitness levels and participants with normal glucose levels, respectively. CONCLUSIONS: LIPA, and not only MVPA, may have beneficial associations with glucose regulation. This is of great clinical and public health importance, not least because it may confer a higher compliance rate to regular PA. PMID- 26900672 TI - Gamma band oscillations: a key to understanding schizophrenia symptoms and neural circuit abnormalities. AB - PURPOSE OF REVIEW: We review our current understanding of abnormal gamma band oscillations in schizophrenia, their association with symptoms and the underlying cortical circuit abnormality, with a particular focus on the role of fast-spiking parvalbumin gamma-aminobutyric acid (GABA) neurons in the disease state. RECENT FINDINGS: Clinical electrophysiological studies of schizophrenia patients and pharmacological models of the disorder show an increase in spontaneous gamma band activity (not stimulus-evoked) measures. These findings provide a crucial link between preclinical and clinical work examining the role of gamma band activity in schizophrenia. MRI-based experiments measuring cortical GABA provides evidence supporting impaired GABAergic neurotransmission in schizophrenia patients, which is correlated with gamma band activity level. Several studies suggest that stimulation of the cortical circuitry, directly or via subcortical structures, has the potential to modulate cortical gamma activity, and improve cognitive function. SUMMARY: Abnormal gamma band activity is observed in patients with schizophrenia and disease models in animals, and is suggested to underlie the psychosis and cognitive/perceptual deficits. Convergent evidence from both clinical and preclinical studies suggest the central factor in gamma band abnormalities is impaired GABAergic neurotransmission, particularly in a subclass of neurons which express parvalbumin. Rescue of gamma band abnormalities presents an intriguing option for therapeutic intervention. PMID- 26900675 TI - PREVALENCE OF MYD88 L265P MUTATION IN HISTOLOGICALLY PROVEN, DIFFUSE LARGE B-CELL VITREORETINAL LYMPHOMA. AB - PURPOSE: Myeloid differentiation primary response gene 88 (MYD88) is a universal adaptor protein in the innate immune system. When associated with a proline for leucine substitution mutation at position 265 (L265P), the protein becomes constitutively activated, amplifying the intracellular pro-inflammatory signal. Recently, we reported two cases of vitreoretinal lymphoma (VRL) that were positive for the mutation. The purpose of this study was to determine prevalence of the MYD88 L265P mutation in a larger series of VRL. METHODS: Retrospective chart review of 25 patients with histologically confirmed VRL evaluated at Mayo Clinic, Rochester, between January 2000 and March 2015. Paraffin-embedded blocks from the vitreous were submitted for polymerase chain reaction testing of the L265P mutation. RESULTS: The mutation was positive in 82.4% of all VRL cases and 86.7% of primary VRL cases. The minimum necessary DNA concentration needed for the polymerase chain reaction assay was 4.93 ng/mL. CONCLUSION: MYD88 gene analysis is a helpful ancillary tool for diagnosing VRL. It often requires fewer cells than flow cytometry or cytology and may be especially useful in early cases where a sufficient number of cells may not be available. PMID- 26900676 TI - Correspondence. PMID- 26900677 TI - Adolescent weight and height are predictors of specific non-Hodgkin lymphoma subtypes among a cohort of 2,352,988 individuals aged 16 to 19 years. AB - BACKGROUND: The age-adjusted annual incidence of non-Hodgkin lymphoma (NHL) has risen worldwide. This trend may be affected by the secular increase in height and the sharp upswing in adolescent overweight; these drive increased insulinlike growth factor 1 and chronic inflammation, which may play an etiologic role. This study examined the association of the body mass index (BMI) and height of adolescents with NHL subtypes, which have been insufficiently evaluated. METHODS: Health-related data on 2,352,988 Israeli adolescents, aged 16 to 19 years, who were examined between 1967 and 2011 were linked to the Israel National Cancer Registry to derive the NHL incidence up to December 31, 2012 (4021 cases). Cox proportional hazards modeling was used to estimate the multivariate-adjusted hazard ratio (HR) for NHL subtypes associated with the BMI and height of adolescents. RESULTS: Adolescent overweight and obesity were associated with an HR of 1.25 (95% confidence interval [CI], 1.13-1.37; P = 1.14 * 10(-5) ) for NHL in comparison with normal weight. There was a graded association of height with NHL (P = 4.29 * 10(-9) ), with the tallest adolescents (>= 95th percentile vs 25th to < 50th percentiles [US Centers for Disease Control and Prevention]) exhibiting an HR of 1.28 (95% CI, 1.04-1.56). Marginal zone lymphoma, primary cutaneous lymphoma (PCL), and diffuse large B-cell lymphoma (DLBCL) showed the strongest associations for overweight/obesity, and DLBCL and PCL showed the strongest associations for height. CONCLUSIONS: The findings of this large cohort study add to the growing body of evidence showing that higher body weight and taller stature during adolescence are associated with an increased risk of NHL and may modestly contribute to its increasing incidence. Further studies are needed to elucidate the mechanisms linking anthropometric measures and NHL risk. PMID- 26900679 TI - Dendrite-Free Lithium Deposition Induced by Uniformly Distributed Lithium Ions for Efficient Lithium Metal Batteries. AB - Li dendrite-free growth is achieved by employing glass fiber with large polar functional groups as the interlayer of Li metal anode and separator to uniformly distribute Li ions. The evenly distributed Li ions render the dendrite-free Li deposits at high rates (10 mA cm(-2)) and high lithiation capacity (2.0 mAh cm( 2)). PMID- 26900678 TI - A multisample dissolution dynamic nuclear polarization system for serial injections in small animals. AB - PURPOSE: Several in vivo applications of dissolution dynamic nuclear polarization (DNP) require rapid successive injections of hyperpolarized substrates. Here we present the design and performance of a custom-built multisample dissolution DNP setup for small animal research. METHODS: The DNP setup consists of a commercial wide-bore magnet charged to 3.35 T, a cryostat, a 94-GHz microwave source, and a custom-built skeleton that accommodates four identical sample sticks. Each sample stick features a dissolver locked into the skeleton port and a lifter, which permits moving the sample cup out of the liquid helium bath for dissolution. RESULTS: The dissolution of the first sample was triggered after 2 hours of polarization buildup during single-shot operation of the cryostat. Thereafter, a time window of 75-90 min was available to dissolve the remaining three polarized samples. The average liquid state polarization over all four sticks was measured as 18.7% +/- 2.3% for [1-13C] pyruvate 30 s after dissolution. In vivo applicability of the setup using serial injections of [1-13C] pyruvate to study cardiac metabolism in rats revealed good reproducibility. CONCLUSION: The proposed four-sample DNP insert provides reproducible liquid state polarization of [1-13C] pyruvate and allows for rapid repeat injections in small animals. Magn Reson Med 77:904-910, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 26900681 TI - Identification of Differentially Expressed Genes Related to Dehydration Resistance in a Highly Drought-Tolerant Pear, Pyrus betulaefolia, as through RNA Seq. AB - Drought is a major abiotic stress that affects plant growth, development and productivity. Pear is one of the most important deciduous fruit trees in the world, but the mechanisms of drought tolerance in this plant are still unclear. To better understand the molecular basis regarding drought stress response, RNA seq was performed on samples collected before and after dehydration in Pyrus betulaefolia. In total, 19,532 differentially expressed genes (DEGs) were identified. These genes were annotated into 144 Gene Ontology (GO) terms and 18 clusters of orthologous groups (COG) involved in 129 Kyoto Encyclopedia of Genes and Genomes (KEGG) defined pathways. These DEGs comprised 49 (26 up-regulated, 23 down-regulated), 248 (166 up-regulated, 82 down-regulated), 3483 (1295 up regulated, 2188 down-regulated), 1455 (1065 up-regulated, 390 down-regulated) genes from the 1 h, 3 h and 6 h dehydration-treated samples and a 24 h recovery samples, respectively. RNA-seq was validated by analyzing the expresson patterns of randomly selected 16 DEGs by quantitative real-time PCR. Photosynthesis, signal transduction, innate immune response, protein phosphorylation, response to water, response to biotic stimulus, and plant hormone signal transduction were the most significantly enriched GO categories amongst the DEGs. A total of 637 transcription factors were shown to be dehydration responsive. In addition, a number of genes involved in the metabolism and signaling of hormones were significantly affected by the dehydration stress. This dataset provides valuable information regarding the Pyrus betulaefolia transcriptome changes in response to dehydration and may promote identification and functional analysis of potential genes that could be used for improving drought tolerance via genetic engineering of non-model, but economically-important, perennial species. PMID- 26900682 TI - Bcl6 Is Required for Somatic Hypermutation and Gene Conversion in Chicken DT40 Cells. AB - The activation induced cytosine deaminase (AID) mediates diversification of B cell immunoglobulin genes by the three distinct yet related processes of somatic hypermutation (SHM), class switch recombination (CSR), and gene conversion (GCV). SHM occurs in germinal center B cells, and the transcription factor Bcl6 is a key regulator of the germinal center B cell gene expression program, including expression of AID. To test the hypothesis that Bcl6 function is important for the process of SHM, we compared WT chicken DT40 B cells, which constitutively perform SHM/GCV, to their Bcl6-deficient counterparts. We found that Bcl6-deficient DT40 cells were unable to perform SHM and GCV despite enforced high level expression of AID and substantial levels of AID in the nucleus of the cells. To gain mechanistic insight into the GCV/SHM dependency on Bcl6, transcriptional features of a highly expressed SHM target gene were analyzed in Bcl6-sufficient and deficient DT40 cells. No defect was observed in the accumulation of single stranded DNA in the target gene as a result of Bcl6 deficiency. In contrast, association of Spt5, an RNA polymerase II (Pol II) and AID binding factor, was strongly reduced at the target gene body relative to the transcription start site in Bcl6-deficient cells as compared to WT cells. However, partial reconstitution of Bcl6 function substantially reconstituted Spt5 association with the target gene body but did not restore detectable SHM. Our observations suggest that in the absence of Bcl6, Spt5 fails to associate efficiently with Pol II at SHM targets, perhaps precluding robust AID action on the SHM target DNA. Our data also suggest, however, that Spt5 binding is not sufficient for SHM of a target gene even in DT40 cells with strong expression of AID. PMID- 26900683 TI - Applicability and Efficiency of NGS in Routine Diagnosis: In-Depth Performance Analysis of a Complete Workflow for CFTR Mutation Analysis. AB - BACKGROUND: Actually, about 2000 sequence variations have been documented in the CFTR gene requiring extensive and multi-step genetic testing in the diagnosis of cystic fibrosis and CFTR-related disorders. We present a two phases study, with validation and performance monitoring, of a single experiment methodology based on multiplex PCR and high throughput sequencing that allows detection of all variants, including large rearrangements, affecting the coding regions plus three deep intronic loci. METHODS: A total of 340 samples, including 257 patients and 83 previously characterized control samples, were sequenced in 17 MiSeq runs and analyzed with two bioinformatic pipelines in routine diagnostic conditions. We obtained 100% coverage for all the target regions in every tested sample. RESULTS: We correctly identified all the 87 known variants in the control samples and successfully confirmed the 62 variants identified among the patients without observing false positive results. Large rearrangements were identified in 18/18 control samples. Only 17 patient samples showed false positive signals (6.6%), 12 of which showed a borderline result for a single amplicon. We also demonstrated the ability of the assay to detect allele specific dropout of amplicons when a sequence variation occurs at a primer binding site thus limiting the risk for false negative results. CONCLUSIONS: We described here the first NGS workflow for CFTR routine analysis that demonstrated equivalent diagnostic performances compared to Sanger sequencing and multiplex ligation-dependent probe amplification. This study illustrates the advantages of NGS in term of scalability, workload reduction and cost-effectiveness in combination with an improvement of the overall data quality due to the simultaneous detection of SNVs and large rearrangements. PMID- 26900685 TI - Early Decision-Making in Drug Development: The Potential Role of Pharmaco-EEG and Pharmaco-Sleep. AB - The pharmaceutical industry has been suffering from low clinical success rates of new drugs for some time with particularly high attrition in early clinical development, especially for drugs aimed at central targets. Both pharmaco electroencephalography (EEG) and pharmaco-sleep, along with other biomarker techniques, have significant potential to assist with this problem by enabling early decisions to be made about the likelihood of a compound proving successful in the clinic. This paper discusses the role and points of application of biomarker techniques in early drug development. It proposes a framework for the use of pharmaco-EEG and pharmaco-sleep in drug development that (i) relies on the combination of preclinical data and an understanding of translatability to generate robust hypotheses for testing in early clinical studies and (ii) is backed up by a clear decision-making process. The areas that need further development before this framework can be put fully into practice are discussed, along with some possible routes by which this could be achieved through precompetitive co-operation within the industry. PMID- 26900684 TI - Sustainable Soil Washing: Shredded Card Filtration of Potentially Toxic Elements after Leaching from Soil Using Organic Acid Solutions. AB - Shredded card (SC) was assessed for use as a sorbent of potentially toxic elements (PTE) carried from contaminated soil in various leachates (oxalic acid, formic acid, CaCl2, water). We further assessed SC for retention of PTE, using acidified water (pH 3.4). Vertical columns and a peristaltic pump were used to leach PTE from soils (O and A/B horizons) before passing through SC. Sorption onto SC was studied by comparing leachates, and by monitoring total PTE contents on SC before and after leaching. SC buffers against acidic soil conditions that promote metals solubility; considerable increases in solution pH (+4.49) were observed. Greatest differences in solution PTE content after leaching with/without SC occurred for Pb. In oxalic acid, As, Cd, Pb showed a high level of sorption (25, 15, and 58x more of the respective PTE in leachates without SC). In formic acid, Pb sorption was highly efficient (219x more Pb in leachate without SC). In water, only Pb showed high sorption (191x more Pb in leachate without SC). In desorption experiments, release of PTE from SC varied according to the source of PTE (organic/mineral soil), and type of solvent used. Arsenic was the PTE most readily leached in desorption experiments. Low As sorption from water was followed by fast release (70% As released from SC). A high rate of Cd sorption from organic acid solutions was followed by strong retention (~12% Cd desorption). SC also retained Pb after sorption from water, with subsequent losses of <=8.5% of total bound Pb. The proposed use of this material is for the filtration of PTE from extract solution following soil washing. Low-molecular mass organic acids offer a less destructive, biodegradable alternative to strong inorganic acids for soil washing. PMID- 26900686 TI - Insomnia and Relationship with Anxiety in University Students: A Cross-Sectional Designed Study. AB - PURPOSE: Sleep disorders (SDs) are now recognized as a public health concern with considerable psychiatric and societal consequences specifically on the academic life of students. The aims of this study were to assess SDs in a group of university students in Lebanon and to examine the relationship between SDs and anxiety. METHODS: An observational cross-sectional study was conducted at Saint Joseph University, Lebanon, during the academic year 2013-2014. Four questionnaires were face-to-face administered to 462 students after obtaining their written consent: Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and Generalized Anxiety Disorder 7 item scale (GAD-7). RESULTS: The prevalence of clinically significant insomnia was 10.6% (95% CI: 7.8-13.4%), more frequent in first year students. ISI mean score was 10.06 (SD = 3.76). 37.1% of the participants were poor sleepers. Excessive daytime sleepiness (EDS) and poor sleep were significantly more frequent among participants with clinical insomnia (p = 0.031 and 0.001 respectively). Clinically significant anxiety was more frequent in students suffering from clinical insomnia (p = 0.006) and in poor sleepers (p = 0.003). 50.8% of the participants with clinically significant anxiety presented EDS versus 30.9% of those with no clinically significant anxiety (p<0.0001). CONCLUSIONS: The magnitude of SDs in this sample of Lebanese university students demonstrate the importance of examining sleep health in this population. Moreover, the link between SD and anxiety reminds us of the importance of treating anxiety as soon as detected and not simply targeting the reduction of sleep problems. PMID- 26900687 TI - The Mare Model to Study the Effects of Ovarian Dynamics on Preantral Follicle Features. AB - Ovarian tissue collected by biopsy procedures allows the performance of many studies with clinical applications in the field of female fertility preservation. The aim of the present study was to investigate the influence of reproductive phase (anestrous vs. diestrous) and ovarian structures (antral follicles and corpus luteum) on the quality, class distribution, number, and density of preantral follicles, and stromal cell density. Ovarian fragments were harvested by biopsy pick-up procedures from mares and submitted to histological analysis. The mean preantral follicle and ovarian stromal cell densities were greater in the diestrous phase and a positive correlation of stromal cell density with the number and density of preantral follicles was observed. The mean area (mm2) of ovarian structures increased in the diestrous phase and had positive correlations with number of preantral follicles, follicle density, and stromal cell density. Biopsy fragments collected from ovaries containing an active corpus luteum had a higher follicle density, stromal cell density, and proportion of normal preantral follicles. In conclusion, our results showed: (1) the diestrous phase influenced positively the preantral follicle quality, class distribution, and follicle and stromal cell densities; (2) the area of ovarian structures was positively correlated with the follicle and stromal cell densities; and (3) the presence of an active corpus luteum had a positive effect on the quality of preantral follicles, and follicle and stromal densities. Therefore, herein we demonstrate that the presence of key ovarian structures favors the harvest of ovarian fragments containing an appropriate number of healthy preantral follicles. PMID- 26900689 TI - Predicting Thermodynamic Properties of PBXTHs with New Quantum Topological Indexes. AB - Novel group quantitative structure-property relationship (QSPR) models on the thermodynamic properties of PBXTHs were presented, by the multiple linear regression (MLR) analysis method. Four thermodynamic properties were studied: the entropy (Stheta), the standard enthalpy of formation (DeltafHtheta), the standard Gibbs energy of formation (DeltafGtheta), and the relative standard Gibbs energy of formation (DeltaRGtheta). The results by the formula indicate that the calculated and predicted data in this study are in good agreement with those in literature and the deviation is within the experimental errors. To validate the estimation reliability for internal samples and the predictive ability for other samples, leave-one-out (LOO) cross validation (CV) and external validation were performed, and the results show that the models are satisfactory. PMID- 26900688 TI - Seasonal Dynamics of Phlebotomine Sand Fly Species Proven Vectors of Mediterranean Leishmaniasis Caused by Leishmania infantum. AB - BACKGROUND: The recent geographical expansion of phlebotomine vectors of Leishmania infantum in the Mediterranean subregion has been attributed to ongoing climate changes. At these latitudes, the activity of sand flies is typically seasonal; because seasonal phenomena are also sensitive to general variations in climate, current phenological data sets can provide a baseline for continuing investigations on sand fly population dynamics that may impact on future scenarios of leishmaniasis transmission. With this aim, in 2011-2013 a consortium of partners from eight Mediterranean countries carried out entomological investigations in sites where L. infantum transmission was recently reported. METHODS/PRINCIPAL FINDINGS: A common protocol for sand fly collection included monthly captures by CDC light traps, complemented by sticky traps in most of the sites. Collections were replicated for more than one season in order to reduce the effects of local weather events. In each site, the trapping effort was left unchanged throughout the survey to legitimate inter-seasonal comparisons. Data from 99,000 collected specimens were analyzed, resulting in the description of seasonal dynamics of 56,000 sand flies belonging to L. infantum vector species throughout a wide geographical area, namely P. perniciosus (Portugal, Spain and Italy), P. ariasi (France), P. neglectus (Greece), P. tobbi (Cyprus and Turkey), P. balcanicus and P. kandelakii (Georgia). Time of sand fly appearance/disappearance in collections differed between sites, and seasonal densities showed variations in each site. Significant correlations were found between latitude/mean annual temperature of sites and i) the first month of sand fly appearance, that ranged from early April to the first half of June; ii) the type of density trend, varying from a single peak in July/August to multiple peaks increasing in magnitude from May through September. A 3-modal trend, recorded for P. tobbi in Cyprus, represents a novel finding for a L. infantum vector. Adults ended the activity starting from mid September through November, without significant correlation with latitude/mean annual temperature of sites. The period of potential exposure to L.infantum in the Mediterranean subregion, as inferred by adult densities calculated from 3 years, 37 sites and 6 competent vector species, was associated to a regular bell-shaped density curve having a wide peak center encompassing the July-September period, and falling between early May to late October for more than 99% of values. Apparently no risk for leishmaniasis transmission took place from December through March in the years considered. We found a common pattern of nocturnal females activity, whose density peaked between 11 pm and 2 am. CONCLUSIONS: Despite annual variations, multiple collections performed over consecutive years provided homogeneous patterns of the potential behavior of leishmaniasis vectors in selected sites, which we propose may represent sentinel areas for future monitoring. In the investigated years, higher potential risk for L. infantum transmission in the Mediterranean was identified in the June-October period (97% relative vector density), however such risk was not equally distributed throughout the region, since density waves of adults occurred earlier and were more frequent in southern territories. PMID- 26900690 TI - Effects of Caricaturing in Shape or Color on Familiarity Decisions for Familiar and Unfamiliar Faces. AB - Recent evidence suggests that while reflectance information (including color) may be more diagnostic for familiar face recognition, shape may be more diagnostic for unfamiliar face identity processing. Moreover, event-related potential (ERP) findings suggest an earlier onset for neural processing of facial shape compared to reflectance. In the current study, we aimed to explore specifically the roles of facial shape and color in a familiarity decision task using pre-experimentally familiar (famous) and unfamiliar faces that were caricatured either in shape only, color-only, or both (full; shape + color) by 15%, 30%, or 45%. We recorded accuracies, mean reaction times, and face-sensitive ERPs. Performance data revealed that shape caricaturing facilitated identity processing for unfamiliar faces only. In the ERP data, such effects of shape caricaturing emerged earlier than those of color caricaturing. Unsurprisingly, ERP effects were accentuated for larger levels of caricaturing. Overall, our findings corroborate the importance of shape for identity processing of unfamiliar faces and demonstrate an earlier onset of neural processing for facial shape compared to color. PMID- 26900691 TI - Renal Function Trajectories in Patients with Prior Improved eGFR Slopes and Risk of Death. AB - BACKGROUND: Multiple prior studies demonstrated that patients with early Chronic Kidney Disease (CKD) and positive estimated Glomerular Filtration Rate (eGFR) slopes experience increased risk of death. We sought to characterize patients with positive eGFR slopes, examine the renal function trajectory that follows the time period where positive slope is observed, and examine the association between different trajectories and risk of death. METHODS AND FINDINGS: We built a cohort of 204,132 United States veterans with early CKD stage 3; eGFR slopes were defined based on Bayesian mixed-effects models using outpatient eGFR measurements between October 1999 and September 2004; to build renal function trajectories, patients were followed longitudinally thereafter (from October 2004) until September 2013. There were 41,410 (20.29%) patients with positive eGFR slope and they exhibited increased risk of death compared to patients with stable eGFR slope (HR = 1.33, CI:1.31-1.35). There was an inverse graded association between severity of albuminuria and the odds of positive eGFR slope (OR = 0.94, CI:0.90 0.98, and OR = 0.76, CI:0.69-0.84 for microalbuminuria and albuminuria; respectively). Following the time period where positive eGFR slope is observed, we characterized 4 trajectory phenotypes: high eGFR intercept and positive trajectory (HIPT) (12.42%), intermediate intercept and mild negative trajectory (IIMNT) (60.04%), low intercept and fast negative trajectory (LIFNT)(23.33%), and high intercept and fast negative trajectory (HIFNT) (4.20%). Compared to IIMNT (reference group), HIPT is associated with younger age, dementia, HIV, chronic lung disease, peripheral artery disease, weight loss, and inversely associated with albuminuria; LIFNT and HIFNT were associated with diabetes, hypertension, cardiovascular disease, peripheral artery disease, and albuminuria. The risk of death at 9 years was lowest in IIMNT (HR = 1.12, CI:1.09-1.14), highest in HIPT (HR = 1.71, CI:1.63-1.79), and intermediate in LIFNT (HR = 1.36, CI:1.32-1.40) and HIFNT (HR = 1.56, CI:1.45-1.68). CONCLUSIONS: Our results demonstrate that patients with positive eGFR slopes, when followed over longer period of time, follow 4 distinct trajectory phenotypes that have distinct demographic and clinical correlates and are differentially associated with risk of death. PMID- 26900692 TI - Characterization of a Complex Chromosomal Rearrangement Involving a de novo Duplication of 9p and 9q and a Deletion of 9q. AB - Rearrangements of the distal region of 9p are important chromosome imbalances in human beings. Trisomy 9p is the fourth most frequent chromosome anomaly and is a clinically recognizable syndrome. Kleefstra syndrome, previously named 9q subtelomeric deletion syndrome, is either caused by a submicroscopic deletion in 9q34.3 or an intragenic mutation of EHMT1. We report a Mexican male patient with abnormal development, dysmorphism, systemic anomalies and a complex chromosomal rearrangement (CCR). GTG-banding revealed a 46,XY,add(9)(q34.3) karyotype, whereas array analysis resulted in arr[hg19] 9p24.3p23(203,861-11,842,172)*3, 9q34.3(138,959,881-139,753,294)*3, 9q34.3(139,784,913-141,020,389)*1. Array and karyotype analyses were normal in both parents. Partial duplication of 9p is one of the most commonly detected autosomal structural abnormalities in liveborn infants. A microdeletion in 9q34.3 corresponds to Kleefstra syndrome, whereas a microduplication in 9q34.3 shows a great clinical variability. Here, we present a CCR in a patient with multiple congenital anomalies who represents the first case with partial 9p trisomy, partial 9q trisomy and partial 9q monosomy. PMID- 26900693 TI - Identification of an HIV-1 BG Intersubtype Recombinant Form (CRF73_BG), Partially Related to CRF14_BG, Which Is Circulating in Portugal and Spain. AB - HIV-1 exhibits a characteristically high genetic diversity, with the M group, responsible for the pandemic, being classified into nine subtypes, 72 circulating recombinant forms (CRFs) and numerous unique recombinant forms (URFs). Here we characterize the near full-length genome sequence of an HIV-1 BG intersubtype recombinant virus (X3208) collected in Galicia (Northwest Spain) which exhibits a mosaic structure coincident with that of a previously characterized BG recombinant virus (9601_01), collected in Germany and epidemiologically linked to Portugal, and different from currently defined CRFs. Similar recombination patterns were found in partial genome sequences from three other BG recombinant viruses, one newly derived, from a virus collected in Spain, and two retrieved from databases, collected in France and Portugal, respectively. Breakpoint coincidence and clustering in phylogenetic trees of these epidemiologically unlinked viruses allow to define a new HIV-1 CRF (CRF73_BG). CRF73_BG shares one breakpoint in the envelope with CRF14_BG, which circulates in Portugal and Spain, and groups with it in a subtype B envelope fragment, but the greatest part of its genome does not appear to derive from CRF14_BG, although both CRFs share as parental strain the subtype G variant circulating in the Iberian Peninsula. Phylogenetic clustering of partial pol and env segments from viruses collected in Portugal and Spain with X3208 and 9691_01 indicates that CRF73_BG is circulating in both countries, with proportions of around 2-3% Portuguese database HIV-1 isolates clustering with CRF73_BG. The fact that an HIV-1 recombinant virus characterized ten years ago as a URF has been shown to represent a CRF suggests that the number of HIV-1 CRFs may be much greater than currently known. PMID- 26900694 TI - Non-monotonic Response to Monotonic Stimulus: Regulation of Glyoxylate Shunt Gene Expression Dynamics in Mycobacterium tuberculosis. AB - Understanding how dynamical responses of biological networks are constrained by underlying network topology is one of the fundamental goals of systems biology. Here we employ monotone systems theory to formulate a theorem stating necessary conditions for non-monotonic time-response of a biochemical network to a monotonic stimulus. We apply this theorem to analyze the non-monotonic dynamics of the sigmaB-regulated glyoxylate shunt gene expression in Mycobacterium tuberculosis cells exposed to hypoxia. We first demonstrate that the known network structure is inconsistent with observed dynamics. To resolve this inconsistency we employ the formulated theorem, modeling simulations and optimization along with follow-up dynamic experimental measurements. We show a requirement for post-translational modulation of sigmaB activity in order to reconcile the network dynamics with its topology. The results of this analysis make testable experimental predictions and demonstrate wider applicability of the developed methodology to a wide class of biological systems. PMID- 26900695 TI - Delivery Mode, Duration of Labor, and Cord Blood Adiponectin, Leptin, and C Reactive Protein: Results of the Population-Based Ulm Birth Cohort Studies. AB - BACKGROUND: Numerous studies have reported associations between delivery mode and health outcomes in infancy and later life. Previous smaller studies indicated a relationship between delivery mode and newborn inflammation potentially constituting a mediating factor. We aimed to determine the influence of delivery mode and duration of labor on cord blood concentrations of adiponectin, leptin, and high-sensitivity C-reactive protein (hs-CRP). METHODS: In the Ulm SPATZ Health Study, 934 singleton newborns and their mothers were recruited during their hospital stay in the University Medical Center Ulm, Southern Germany, from 04/2012-05/2013. Inflammatory biomarkers were measured by ELISAs (n = 836). Delivery mode was analyzed categorically (elective cesarean (reference), active labor delivery: emergency cesarean, assisted vaginal, and spontaneous vaginal); duration of labor continuously. Following log-transformation, linear regression was used to estimate geometric means ratios (GMR) adjusted for potential confounders for the effects of delivery mode and duration of labor on each biomarker separately. Independent replication was sought in the similarly conducted Ulm Birth Cohort Study recruited from 11/2000-11/2001. RESULTS: Individually, active labor delivery modes as well as increasing duration of labor were associated with higher leptin and hs-CRP concentrations. After mutual adjustment, the associations with delivery modes were attenuated but those for duration of labor remained statistically significant (GMR (95%CI) 1.10 (1.00; 1.21) and 1.15 (1.04; 1.27) for leptin and hs-CRP per hour of labor, respectively). No significant adjusted associations were observed between delivery modes and adiponectin concentrations. These findings were replicated in an independent birth cohort study. CONCLUSIONS: Cord blood leptin and hs-CRP concentrations were associated with duration of labor rather than delivery mode. Further research is warranted to investigate these associations with additional cytokines involved in inflammatory response to delineate the inflammatory profile. Subsequently, research on determinants of these associations and their role in development of chronic disease is needed. PMID- 26900696 TI - Brain Atrophy Correlates with Severe Enlarged Perivascular Spaces in Basal Ganglia among Lacunar Stroke Patients. AB - BACKGROUND: Enlarged perivascular spaces (EPVS) correlate with cognitive impairment and incident dementia. However, etiologies for severe basal ganglia EPVS (BG-EPVS) are still unclear. Our aim was to investigate the independent risk factors for severe BG-EPVS in patients with acute lacunar stroke. METHODS: We prospectively identified patients with lacunar stroke (diameter on DWI <= 20mm) from Jan 2011 to May 2015. Patients with severe BG-EPVS were identified on T2 weighted MRI. Age (+/- 1 year) and sex matched controls were also recruited in the same population (two controls for one case). Vascular risk factors, clinical data, EPVS in centrum semiovale (rated 0 to 4), white matter hyperintensities (WMH) (by Fazekas scale), brain atrophy (rated 0 to 6) were compared between two groups. Logistic regression was performed to determine independent risk factors for severe BG-EPVS. RESULTS: During study period, 89 patients with severe BG-EPVS and 178 matched controls were included. Vascular risk factors did not differ between two groups. Patients with severe BG-EPVS had lower level of HbA1c and diastolic BP at admission, but presented with larger infarct size, more severe WMH (including total WMH, periventricular WMH and deep WMH) and brain atrophy. In logistic regression, brain atrophy (OR = 1.40; 95%CI 1.13, 1.73) and deep WMH (OR = 1.88; 95%CI 1.24, 2.83) were independent risk factors for severe BG-EPVS. CONCLUSIONS: Brain atrophy and deep WMH are independent risk factors for severe BG-EPVS, supporting the hypothesis that brain atrophy may be associated with the development of EPVS in basal ganglia. PMID- 26900697 TI - Galactomannan Testing and the Incidence of Invasive Pulmonary Aspergillosis: A 10 Year Nationwide Population-Based Study in Taiwan. AB - BACKGROUND: The clinical impact of the galactomannan (GM) test for the diagnosis of invasive pulmonary aspergillosis (IPA) is controversial. Our study evaluated the incidence and trends of IPA and GM testing in patients with aspergillus infections. METHODS: We conducted a nationwide inpatient population study using the Taiwan National Health Insurance Research Database. A total of 346 IPA (62.14% male) patients from the years 2002 to 2011 were identified for inclusion in the study. RESULTS: The average incidence of IPA was 1.51 per million person years. Over the study period, we observed an increasing trend from 0.94 to 2.06 per million person-years (P < 0.0001). We observed male predominance in IPA incidence (M/F: 1.85/1.15). Both males and females showed significantly increasing trends of IPA incidence over time (0.87 to 4.55 and 0.36 to 2.07 per million person-years for the males and females, respectively). GM testing for IPA significantly increased from 2002 to 2011, and the GM test was utilized more frequently for males than females. The increase in the incidence of IPA might be positively associated with the increase in GM testing over the past decade. CONCLUSION: The incidence rates of both IPA and GM testing have increased over time. GM testing is recommended for the early diagnosis of patients with suspected aspergillosis. PMID- 26900698 TI - Inter-Segmental Coordination Pattern in Patients with Anterior Cruciate Ligament Deficiency during a Single-Step Descent. AB - Anterior cruciate ligament injury is a debilitating pathology which may alter lower limb coordination pattern in both intact and affected lower extremities during activities of daily living. Emerging evidence supports the notion that kinematic variables may not be a good indicator to differentiate patients with anterior cruciate ligament deficiency during step descent task. The aim of the present study was to examine alterations in kinematics as well as coordination patterns and coordination variability of both limbs of these patients during a single step descent task. Continuous relative phase technique was used to measure coordination pattern and coordination variability between a group of anterior cruciate ligament deficient (n = 23) and a healthy control group (n = 23). A third order polynomial Curve fitting was utilized to provide a curve that best fitted to the data points of coordination pattern and coordination variability of the healthy control group. This was considered as a reference to compare to that of patient group using nonlinear regression analysis. The results of the present study demonstrated an altered coordination pattern of the supporting shank-thigh and the stepping foot-shank couplings in anterior cruciate ligament deficient subjects. It was further noticed that there was an increased coordination variability in foot-shank and shank-thigh couplings of both supporting and stepping legs. There was no significant difference in the hip, knee and ankle joints kinematics in either side of these patients. Anterior cruciate ligament deficient individuals showed altered strategies in both intact and affected legs, with increased coordination variability. Kinematic data did not indicate any significant difference between the two groups. It could be concluded that more sophisticated dynamic approach such as continuous relative phase would uncover discrepancies between the healthy and anterior cruciate ligament deficient individuals. PMID- 26900699 TI - Mechanics in the Production of Mandibular Fractures: A Clinical, Retrospective Case-Control Study. AB - As the mandible is susceptible to fracture, the aim of this study was to use multivariate logistic regression analysis to identify and distinguish various internal factors that may influence the location of mandibular fractures. The study included 1131 patients with maxillofacial fractures during the period from January 2000 to December 2009 to evaluate the association of mandibular fracture location (unilateral symphysis, body, angle, condylar, or bilateral condylar fractures) with various internal factors. Among the 1131 patients, 869 had mandibular fractures. Data on age, sex, soft tissue injuries, dental trauma, and maxillofacial fracture type were collected and analyzed using multivariate logistic regression. In total, 387, 210, 139, 319, and 172 patients were diagnosed with unilateral symphysis, body, angle, unilateral, or bilateral condylar fractures, respectively. The dental trauma in patients with bilateral condylar fractures differed from that in patients with unilateral condylar fractures. Patients with mandibular fracture (unilateral symphysis, body, unilateral or bilateral condylar) possessed an approximately equal risk of soft tissue injuries in the mandible. Patients with either unilateral or bilateral condylar fractures were associated with a low risk of mandibular angle fracture (OR < 1). Similarly, patients with mandibular angle fracture were associated with a low risk of unilateral or bilateral condylar fractures (OR < 1). Moreover, patients with symphysis fracture were associated with a low risk of bilateral condylar fractures (90 of 387 [23.3%], OR 0.899). By contrast, patients with bilateral condylar fractures were associated with a high risk of symphysis fracture (90 of 172 [52.3%], OR 17.38). Patients with condylar fractures, particularly those with bilateral condylar fractures, were infrequently associated with secondary mandibular fractures. Mandibular fractures tended to have less of an association with midfacial fractures. The occurrence of mandibular fractures is strongly correlated with age, sex, soft tissue injuries, dental trauma, and the pattern and position of the maxillofacial fractures in patients. PMID- 26900700 TI - Functional Rescue of Trafficking-Impaired ABCB4 Mutants by Chemical Chaperones. AB - Multidrug resistance protein 3 (MDR3, ABCB4) is a hepatocellular membrane protein that mediates biliary secretion of phosphatidylcholine. Null mutations in ABCB4 gene give rise to severe early-onset cholestatic liver disease. We have previously shown that the disease-associated mutations p.G68R, p.G228R, p.D459H, and p.A934T resulted in retention of ABCB4 in the endoplasmic reticulum, thus failing to target the plasma membrane. In the present study, we tested the ability of two compounds with chaperone-like activity, 4-phenylbutyrate and curcumin, to rescue these ABCB4 mutants by assessing their effects on subcellular localization, protein maturation, and phospholipid efflux capability. Incubation of transfected cells at a reduced temperature (30 degrees C) or exposure to pharmacological doses of either 4-PBA or curcumin restored cell surface expression of mutants G228R and A934T. The delivery of these mutants to the plasma membrane was accompanied by a switch in the ratio of mature to inmature protein forms, leading to a predominant expression of the mature protein. This effect was due to an improvement in the maturation rate and not to the stabilization of the mature forms. Both mutants were also functionally rescued, displaying bile salt-dependent phospholipid efflux activity after addition of 4 PBA or curcumin. Drug-induced rescue was mutant specific, given neither 4-PBA nor curcumin had an effect on the ABCB4 mutants G68R and A934T. Collectively, these data indicate that the functionality of selected trafficking-defective ABCB4 mutants can be recovered by chemical chaperones through restoration of membrane localization, suggesting a potential treatment for patients carrying such mutations. PMID- 26900701 TI - Contributions of EspA Filaments and Curli Fimbriae in Cellular Adherence and Biofilm Formation of Enterohemorrhagic Escherichia coli O157:H7. AB - In Escherichia coli O157:H7 (O157), the filamentous structure of the type III secretion system is produced from the polymerization of the EspA protein. EspA filaments are essential for O157 adherence to epithelial cells. In previous studies, we demonstrated that O157 hha deletion mutants showed increased adherence to HEp-2 cells and produced abundant biofilms. Transcriptional analysis revealed increased expression of espA as well as the csgA gene, which encodes curli fimbriae that are essential for biofilm formation. In the present study, we constructed hha espA, hha csgA, and hha csgA espA deletion mutants to determine the relative importance of EspA and CsgA in O157 adherence to HEp-2 cells and biofilm formation. In vitro adherence assays, conducted at 37 degrees C in a tissue culture medium containing 0.1% glucose, showed that HEp-2 cell adherence required EspA because hha espA and hha csgA espA mutants adhered to HEp-2 cells at higher levels only when complemented with an espA-expressing plasmid. Biofilm assays performed at 28 degrees C in a medium lacking glucose showed dependency of biofilm formation on CsgA; however EspA was not produced under these conditions. Despite production of detectable levels of EspA at 37 degrees C in media supplemented with 0.1% glucose, the biofilm formation occurred independent of EspA. These results indicate dependency of O157 adherence to epithelial cells on EspA filaments, while CsgA promoted biofilm formation under conditions mimicking those found in the environment (low temperature with nutrient limitations) and in the digestive tract of an host animal (higher temperature and low levels of glucose). PMID- 26900702 TI - The Factors Related to CD4+ T-Cell Recovery and Viral Suppression in Patients Who Have Low CD4+ T Cell Counts at the Initiation of HAART: A Retrospective Study of the National HIV Treatment Sub-Database of Zhejiang Province, China, 2014. AB - BACKGROUND: Since China has a unique system of delivering HIV care that includes all patients' records. The factors related to CD4+ T-cell recovery and viral suppression in patients who have low CD4+ T cell counts at the initiation of HAART are understudied in the China despite subsequent virological suppression (viral load < 50 copies/mL) is unknown. METHODS: The authors conducted a retrospective cohort study using data from the national HIV treatment sub database of Zhejiang province to identify records of HIV+ patients. Patient records were included if they were >= 16 years of age, had an initial CD4 count < 100 cells/MUL, were on continuous HAART for at least one year by the end of December 31, 2014; and achieved and maintained continued maximum virological suppression (MVS) (< 50 copies/ml) by 9 months after starting HAART. The primary endpoint for analysis was time to first CD4+ T cell count recovery (>= 200, 350, 500 cells/MUL). Cox proportional hazard regression was used to identify the risk factors for CD4+ T cell count recovery to key thresholds (200-350, 350-500, >= 500 cells/MUL) by the time of last clinical follow-up (whichever occurred first), key thresholds (follow-up date for analysis), with patients still unable to reach the endpoints being censored by the end December 31, 2014 (follow-up date for analysis). RESULTS: Of the 918 patients who were included in the study, and the median CD4+ T cell count was 39 cells/MUL at the baseline. At the end of follow up, 727 (79.2%), 363 (39.5%) and 149 (16.2%) patients had return to >= 200, 350, and 500 cells/MUL, respectively. Kaplan-Meier analysis demonstrated that the rate of patients with CD4+ count recovery to >= 200, 350, and 500 cells/MUL after 1 year on HAART was 43.6, 8.6, and 2.5%, respectively, after 3 years on treatment was 90.8, 46.3, and 17.9%, respectively, and after 5 years on HAART was 97.1, 72.2, and 36.4%, respectively. The median time to return to 200-350, 350-500, >= 500cells/MUL was 1.11, 3.33 and 6.91 years, respectively. Factors of age (aHR = 0.77, 95%CI 0.61-0.97), baseline CD4+ count (aHR = 1.60, 95%CI 1.37-1.86), initial regimens, changes in regimen (aHR = 0.58, 95%CI 0.49-0.69), and inclusion of a cotrimoxazole prophylaxis (aHR = 0.66, 95%CI 0.51-0.85) were associated with CD4+ T cell count recovery. CONCLUSION: The proportion of patients with initially low CD4 counts after nine months of treatment and that achieved continuous virological suppression was greater than 70% for persons with CD4+ count >= 350. Conversely, only 35% of patients recovered to levels of 500 cells/MUL after 5 years of treatment, and levels continued to rise significantly with further long term HAART. Early HAART intervention will be necessary for achieving effective CD4+ T cell responses and optimal immunological function in HIV+ patients. PMID- 26900703 TI - Cytokinin Production by the Rice Blast Fungus Is a Pivotal Requirement for Full Virulence. AB - Plants produce cytokinin (CK) hormones for controlling key developmental processes like source/sink distribution, cell division or programmed cell-death. Some plant pathogens have been shown to produce CKs but the function of this mimicry production by non-tumor inducing pathogens, has yet to be established. Here we identify a gene required for CK biosynthesis, CKS1, in the rice blast fungus Magnaporthe oryzae. The fungal-secreted CKs are likely perceived by the plant during infection since the transcriptional regulation of rice CK-responsive genes is altered in plants infected by the mutants in which CKS1 gene was deleted. Although cks1 mutants showed normal in vitro growth and development, they were severely affected for in planta growth and virulence. Moreover, we showed that the cks1 mutant triggered enhanced induction of plant defenses as manifested by an elevated oxidative burst and expression of defense-related markers. In addition, the contents of sugars and key amino acids for fungal growth were altered in and around the infection site by the cks1 mutant in a different manner than by the control strain. These results suggest that fungal derived CKs are key effectors required for dampening host defenses and affecting sugar and amino acid distribution in and around the infection site. PMID- 26900705 TI - Horizontal Gaze Palsy With Progressive Scoliosis and Severe Keratoconus With a Compound Heterozygous Mutation in ROBO3. AB - The authors report the case of a child with horizontal gaze palsy with progressive scoliosis and keratoconus. ROBO3 analysis identified compound heterozygous mutations. Keratoconus surgical approach resulted in visual acuity improvement in both eyes. The previously unreported occurrence of keratoconus with horizontal gaze palsy with progressive scoliosis suggests that ophthalmologic assessment should search for signs of this ectasia in these patients. PMID- 26900704 TI - Direct Measurements of Oxygen Gradients in Spheroid Culture System Using Electron Parametric Resonance Oximetry. AB - Advanced in vitro culture from tissues of different origin includes three dimensional (3D) organoid micro structures that may mimic conditions in vivo. One example of simple 3D culture is spheroids; ball shaped structures typically used as liver and tumour models. Oxygen is critically important in physiological processes, but is difficult to quantify in 3D culture: and the question arises, how small does a spheroid have to be to have minimal micro-environment formation? This question is of particular importance in the growing field of 3D based models for toxicological assessment. Here, we describe a simple non-invasive approach modified for the quantitative measurement and subsequent evaluation of oxygen gradients in spheroids developed from a non-malignant fish cell line (i.e. RTG-2 cells) using Electron Paramagnetic Resonance (EPR) oximetry. Sonication of the paramagnetic probe Lithium phthalocyanine (LiPc) allows for incorporation of probe particulates into spheroid during its formation. Spectra signal strength after incorporation of probe into spheroid indicated that a volume of 20 MUl of probe (stock solution: 0.10 mg/mL) is sufficient to provide a strong spectra across a range of spheroid sizes. The addition of non-toxic probes (that do not produce or consume oxygen) report on oxygen diffusion throughout the spheroid as a function of size. We provide evidence supporting the use of this model over a range of initial cell seeding densities and spheroid sizes with the production of oxygen distribution as a function of these parameters. In our spheroid model, lower cell seeding densities (~2,500 cells/spheroid) and absolute size (118+/-32 MUm) allow control of factors such as pre-existing stresses (e.g. ~ 2% normoxic/hypoxic interface) for more accurate measurement of treatment response. The applied methodology provides an elegant, widely applicable approach to directly characterize spheroid (and other organoid) cultures in biomedical and toxicological research. PMID- 26900706 TI - Bilateral Combined Hamartomas of the Retina and Retinal Pigment Epithelium as the Presenting Feature of Neurofibromatosis Type 2 (Wishart Type). AB - An 8-week-old healthy female infant manifested leukocoria and reduced vision in the left eye. She was found to have bilateral combined hamartomas of the retina and retinal pigment epithelium. There were no other features of neurofibromatosis type 2 and brain imaging was normal. At 6 months of age, subtle posterior subcapsular lens opacity was noted in the right eye. Genetic testing for neurofibromatosis type 2 was advised but not performed. At 3 years of age, leg weakness with quadriceps atrophy led to neuroimaging and detection of multiple tumors, including bilateral vestibular schwannomas and cervical, thoracic, and lumbar paraspinal schwannomas. Molecular testing revealed a nonsense mutation in the neurofibromatosis type 2 gene. Bilateral combined hamartomas were the presenting feature of a severe phenotype of neurofibromatosis type 2. PMID- 26900707 TI - Unilateral Morning Glory Disc Anomaly With Ipsilateral Limbal Dermoids. AB - The authors present the case of a child with multiple limbal dermoids and morning glory disc anomaly in the right eye. These anomalies are rarely associated and this is the first report of co-occurrence in the same eye in a patient without additional systemic anomalies. PMID- 26900708 TI - Spatial working memory capacity predicts bias in estimates of location. AB - Spatial memory research has attributed systematic bias in location estimates to a combination of a noisy memory trace with a prior structure that people impose on the space. Little is known about intraindividual stability and interindividual variation in these patterns of bias. In the current work, we align recent empirical and theoretical work on working memory capacity limits and spatial memory bias to generate the prediction that those with lower working memory capacity will show greater bias in memory of the location of a single item. Reanalyzing data from a large study of cognitive aging, we find support for this prediction. Fitting separate models to individuals' data revealed a surprising variety of strategies. Some were consistent with Bayesian models of spatial category use, however roughly half of participants biased estimates outward in a way not predicted by current models and others seemed to combine these strategies. These analyses highlight the importance of studying individuals when developing general models of cognition. (PsycINFO Database Record PMID- 26900710 TI - Triazolinediones as Highly Enabling Synthetic Tools. AB - Triazolinediones (TADs) are unique reagents in organic synthesis that have also found wide applications in different research disciplines, in spite of their somewhat "exotic" reputation. In this review, we offer two case studies that demonstrate the possibilities of these versatile and reliable synthetic tools, namely, in the field of polymer science as well as in more recently emerging applications in the field of click chemistry. As the general use of triazolinediones has always been hampered by the limited commercial and synthetic availability of such reagents, we also offer a review of the available TAD reagents, together with a detailed discussion of their synthesis and reactivity. This review thus aims to serve as a practical guide for researchers that are interested in exploiting and further developing the exceptional click-like reactivity of triazolinediones in various applications. PMID- 26900709 TI - Reading Out Single-Molecule Digital RNA and DNA Isothermal Amplification in Nanoliter Volumes with Unmodified Camera Phones. AB - Digital single-molecule technologies are expanding diagnostic capabilities, enabling the ultrasensitive quantification of targets, such as viral load in HIV and hepatitis C infections, by directly counting single molecules. Replacing fluorescent readout with a robust visual readout that can be captured by any unmodified cell phone camera will facilitate the global distribution of diagnostic tests, including in limited-resource settings where the need is greatest. This paper describes a methodology for developing a visual readout system for digital single-molecule amplification of RNA and DNA by (i) selecting colorimetric amplification-indicator dyes that are compatible with the spectral sensitivity of standard mobile phones, and (ii) identifying an optimal ratiometric image-process for a selected dye to achieve a readout that is robust to lighting conditions and camera hardware and provides unambiguous quantitative results, even for colorblind users. We also include an analysis of the limitations of this methodology, and provide a microfluidic approach that can be applied to expand dynamic range and improve reaction performance, allowing ultrasensitive, quantitative measurements at volumes as low as 5 nL. We validate this methodology using SlipChip-based digital single-molecule isothermal amplification with lambdaDNA as a model and hepatitis C viral RNA as a clinically relevant target. The innovative combination of isothermal amplification chemistry in the presence of a judiciously chosen indicator dye and ratiometric image processing with SlipChip technology allowed the sequence-specific visual readout of single nucleic acid molecules in nanoliter volumes with an unmodified cell phone camera. When paired with devices that integrate sample preparation and nucleic acid amplification, this hardware-agnostic approach will increase the affordability and the distribution of quantitative diagnostic and environmental tests. PMID- 26900712 TI - Influence of Anion and Mole Ratio on the Coordination Behavior of an NO2S3 Macrocycle: The Formation of a Dumbbell-Shaped Macrocyclic Cadmium(II) Iodide Complex. AB - Anion and mole ratio dependent formations of cadmium(II) complexes with an NO2S3 macrocycle (L) incorporating a pyridine subunit are reported. When the cadmium(II) salts (1-10 equiv) with different halide ions (Br(-) or I(-)) were reacted with L, CdBr2 afforded a monomer complex, [Cd(L)Br]2[Cd2Br6].CH2Cl2 (1), with three separated parts in the whole mole ratio range: two 1:1 stoichiometric complex cation parts and one Cd2Br6 cluster anion part. After separation of 1 by filtration, [Cd(L)Br]2[CdBr4].CH2Cl2 (2) with similar composition was afforded, except the cluster was isolated from the filtrate. Unlike the CdBr2 complexation, CdI2 afforded the mole ratio dependent products (3-5). Below 2.5 equiv of CdI2, [Cd(L)I]2[CdI4].CH2Cl2 (3) and [Cd(L)I]2[Cd2I6].0.5CH2Cl2 (4) with different cadmium(II) iodide clusters were isolated as kinetic (3) and a thermodynamic (4) products. Notably, the use of 3 equiv or above amount of CdI2 gave a dumbbell shaped complex, {[Cd(L)]2(MU-Cd4I12)} (5), in which two mononuclear macrocyclic complex units are linked by a (MU-Cd4I12)(4-) cluster. To monitor the mole ratio dependency as well as their reactivities, the systematic powder X-ray diffraction (PXRD) analysis has also been applied. PMID- 26900711 TI - Inhibition of Chikungunya Virus-Induced Cell Death by Salicylate-Derived Bryostatin Analogues Provides Additional Evidence for a PKC-Independent Pathway. AB - Chikungunya virus (CHIKV) has been spreading rapidly, with over one million confirmed or suspected cases in the Americas since late 2013. Infection with CHIKV causes devastating arthritic and arthralgic symptoms. Currently, there is no therapy to treat this disease, and the only medications focus on relief of symptoms. Recently, protein kinase C (PKC) modulators have been reported to inhibit CHIKV-induced cell death in cell assays. The salicylate-derived bryostatin analogues described here are structurally simplified PKC modulators that are more synthetically accessible than the natural product bryostatin 1, a PKC modulator and clinical lead for the treatment of cancer, Alzheimer's disease, and HIV eradication. Evaluation of the anti-CHIKV activity of these salicylate derived bryostatin analogues in cell culture indicates that they are among the most potent cell-protective agents reported to date. Given that they are more accessible and significantly more active than the parent natural product, they represent new therapeutic leads for controlling CHIKV infection. Significantly, these analogues also provide evidence for the involvement of a PKC-independent pathway. This adds a fundamentally distinct aspect to the importance or involvement of PKC modulation in inhibition of chikungunya virus replication, a topic of recent and growing interest. PMID- 26900713 TI - Chemically Induced Cryptic Sesquiterpenoids and Expression of Sesquiterpene Cyclases in Botrytis cinerea Revealed New Sporogenic (+)-4-Epieremophil-9-en-11 ols. AB - The sequencing of the genomes of the B05.10 and T4 strains of the fungus Botrytis cinerea revealed an abundance of novel biosynthetic gene clusters, the majority of which were unexpected on the basis of the previous analyses of the fermentation of these and closely related species. By systematic alteration of easy accessible cultivation parameters, using chemical induction with copper sulfate, we have found a cryptic sesquiterpenoid family with new structures related to eremophil-9-ene, which had the basic structure of the sesquiterpene (+)-5-epiaristolochene ((+)-4-epieremophil-9-ene). An expression study of the sesquiterpene cyclase genes present in the Botrytis cinerea genome, under culture conditions, is reported. In general, a 3 day delay and a higher BcSTC genes expression were observed when copper (5 ppm) was fed to the fermentation broth. In addition, to the observed effect on the BcBOT2 (BcSTC1) gene, involved in the biosynthesis of the botrydial toxin, a higher expression level for BcSTC3 and BcSTC4 was observed with respect to the control in the strain B05.10. Interestingly, under copper conditions, the BcSTC4 gene was the most expressed gene in the Botrytis cinerea UCA992 strain. In vitro evaluation of the biological role of these metabolites indicates that they contributed to the conidial development in B. cinerea and appear to be involved in self-regulation of the production of asexual spores. Furthermore, they promoted the formation of complex appressoria or infection cushions. PMID- 26900714 TI - Photoinduced Electron Transfer within Supramolecular Donor-Acceptor Peptide Nanostructures under Aqueous Conditions. AB - We report the synthesis, self-assembly, and electron transfer capabilities of peptide-based electron donor-acceptor molecules and supramolecular nanostructures. These modified peptides contain pi-conjugated oligothiophene electron donor cores that are peripherally substituted with naphthalene diimide electron acceptors installed via imidation of site-specific lysine residues. These molecules self-assemble into one-dimensional nanostructures in aqueous media, as shown through steady-state absorption, photoluminescence, and circular dichroism spectra, as well as transmission electron microscopy. Excitation of the oligothiophene donor moieties results in electron transfer to the acceptor units, ultimately creating polar, charge-separated states that persist for over a nanosecond as observed with transient absorption spectroscopy. This study demonstrates how transient electric fields can be engineered into aqueous nanomaterials of biomedical relevance through external, temporally controlled photonic inputs. PMID- 26900715 TI - Mechanisms of Chromate, Selenate, and Sulfate Adsorption on Al-Substituted Ferrihydrite: Implications for Ferrihydrite Surface Structure and Reactivity. AB - Ferrihydrite is a nanocrystalline Fe (hydr)oxide and important sink for environmental contaminants. Although Fe (hydr)oxides are rarely pure in natural systems, little is known about the effects of structural impurities such as Al on the surface properties and reactivity of ferrihydrite. In this study, we characterized the adsorption mechanisms of chromate, selenate, and sulfate on Al substituted ferrihydrite (0, 6, 12, 18, and 24 mol % Al) using in situ attenuated total reflection Fourier transform infrared spectroscopy. Spectral data sets recorded as a function of pH were processed using a multivariate curve resolution technique to identify which types of surface species form and to generate their concentration profiles as a function of pH and Al content. Results show a significant increase in relative fraction of outer-sphere complexes for all three oxyanions with increasing Al substitution. In addition, the effect of Al substitution is found to be mechanism-specific in the case of chromate, with bidentate complexes disproportionately suppressed over monodentate complexes at higher Al contents. Overall, our findings have important implications for the fate of chromate, selenate, and sulfate in subsurface environments and offer new insight into the surface reactivity of Al-ferrihydrite. PMID- 26900716 TI - Insights into the Inhibitory Mechanism of D13-9001 to the Multidrug Transporter AcrB through Molecular Dynamics Simulations. AB - The resistance-nodulation-cell division transporter AcrB is responsible for energy transduction and substrate recognition in the tripartite AcrAB-TolC efflux system in Escherichia coli. Despite a broad substrate specificity, only a few compounds have been cocrystallized with AcrB inside the distal binding pocket (DBP), including doxorubicin (DOX) and D13-9001. D13-9001 is a promising efflux pump inhibitor that potentiates the efficacy of a wide variety of antibiotics. To understand its inhibition effect under the framework of functional rotating mechanism, we performed targeted and steered molecular dynamics simulations to compare the binding and extrusion processes of this inhibitor and the substrate DOX in AcrB. The results demonstrate that, with respect to DOX, the interaction of D13-9001 with the hydrophobic trap results in delayed disassociation from the DBP. Notably, the detachment of D13-9001 is tightly correlated with the side chain reorientation of Phe628 and large-scale displacement of Tyr327. Furthermore, the inhibitor induces much more significant conformational changes at the exit gate than DOX does, thereby causing higher energy cost for extrusion and contributing to the inhibitory effect in addition to the tight binding at DBP. PMID- 26900717 TI - The Nature of the Donor Motif in Acceptor-Bridge-Donor Dyes as an Influence in the Electron Photo-Injection Mechanism in DSSCs. AB - The combination and balance of acceptor(A)-bridge-donor(D) architecture of molecules confer suitable attributes and/or properties to act as efficient light harvesting and sensitizers in dye sensitized solar cells (DSSCs). An important process in a DSSC performance is the electron photoinjection (PI) mechanism which can take place either via type I (indirect), that consists in injecting from the excited state of the dye to the semiconductor, or type II (direct), where the PI is from the ground state of the dye to the semiconductor upon photoexcitation. Here, we present a computational study about the role of the donor motif in the PI mechanisms displayed from a family of 11 A-bridge-D structured dyes to a (TiO2)15 anatase cluster. To this end, different donor motifs (D1-D11) were evaluated while the A and bridge motifs remained the same. All the computations were carried out within the DFT framework, using the B3LYP, PW91, PBE, M06L and CAM-B3LYP functionals. The 6-31G(d) basis set was employed for nonmetallic atoms and the LANL2DZ pseudopotential for Ti atoms. The solvation effects were incorporated using the polarized continuum model (PCM) for acetonitrile. As benchmark systems, alizarin and naphthalenediol dyes were analyzed, as they are known to undergo Type I and Type II PI pathways in DSSCs, respectively. Donors in the studied family of dyes could influence to drive Type I or II PI since it was found that D2 could show some Type II PI route, showing a new absorption band, although with CAM-B3LYP this shows a very low oscillator strength, while the remaining dyes behave according to Type I photoinjectors. Finally, the photovoltaic parameters that govern the light absorption process were evaluated, as the use of these criteria could be applied to predict the efficiency of the studied dyes in DSSCs devices. PMID- 26900718 TI - Dodecaborate-Functionalized Anchor Dyes for Cyclodextrin-Based Indicator Displacement Applications. AB - A new type of water-soluble anchor dyes, that is, dyes which carry an auxiliary unit for strong binding to macrocyclic host molecules, has been synthesized. It consists of 7-nitrobenzofurazan (NBD) as a dye and the dodecaborate cluster (B12H11R) as a dianionic, globular, and purely inorganic anchoring group for cyclodextrins (Ka > 10(5) M(-1)). The synthesized dodecaborate-substituted dyes show marked changes in their photophysical properties (UV-vis and fluorescence) upon complexation with cyclodextrins (beta-CD and gamma-CD), such that the resulting host.dye complexes (1:1 stoichiometry) present sensitive reporter pairs for indicator displacement applications. PMID- 26900719 TI - Optimal therapy for polycythemia vera and essential thrombocythemia: Preferred use of interferon therapy based on phase 2 trials. AB - OBJECTIVES: To determine the value of recombinant interferon-alfa (rIFNalpha) in the treatment of polycythemia vera (PV) and essential thrombocythemia (ET) based on its biological activities and phase 2 clinical studies, pending completion of phase 3 trials; to determine importance of the Internet in patient decision making in treatment selection. RESULTS: The value of rIFNalpha in PV and ET is based upon its biological effects on PV stem cells and megakaryocyte proliferation. Single-arm trials are useful for life-threatening diseases when there are relatively few patients to evaluate endpoints, such as rIFNalpha treatment of PV and ET. Proper diagnostic criteria are mandatory; for PV, the current World Health Organization criteria emphasizing increased hemoglobin values exclude approximately one-third of eligible patients. Importance of these data: Single-arm studies in diseases exemplified by rIFNalpha in PV require updated diagnostic criteria for research and for clinical practice. The influence of the Internet on patient decisions for treatment is noteworthy. CONCLUSION: The biologic basis for selecting therapy is exemplified by rIFNalpha in treating PV and ET. Current single-arm studies of rIFNalpha in PV and ET are relevant and acceptable. The importance of the Internet in patient decision-making is important. PMID- 26900720 TI - Sulforaphane improves oxidative status without attenuating the inflammatory response or cardiac impairment induced by ischemia-reperfusion in rats. AB - Sulforaphane, a natural isothiocyanate, demonstrates cardioprotection associated with its capacity to stimulate endogenous antioxidants and to inhibit inflammation. The aim of this study was to investigate whether sulforaphane is capable of attenuating oxidative stress and inflammatory responses through the TLR4/MyD88/NFkappaB pathway, and thereby could modulate post-ischemic ventricular function in isolated rat hearts submitted to ischemia and reperfusion. Male Wistar rats received sulforaphane (10 mg.kg(-1).day(-1)) or vehicle i.p. for 3 days. Global ischemia was performed using isolated hearts, 24 h after the last injection, by interruption of the perfusion flow. The protocol included a 20 min pre-ischemic period followed by 20 min of ischemia and a 20 min reperfusion. Although no changes in mechanical function were observed, sulforaphane induced a significant increase in superoxide dismutase and heme oxygenase-1 expression (both 66%) and significantly reduced reactive oxygen species levels (7%). No differences were observed for catalase and glutathione peroxidase expression or their activities, nor for thioredoxin reductase, glutaredoxin reductase and glutathione-S-transferase. No differences were found in lipid peroxidation or TLR4, MyD88, and NF-kappaB expression. In conclusion, although sulforaphane was able to stimulate endogenous antioxidants modestly, this result did not impact inflammatory signaling or cardiac function of hearts submitted to ischemia and reperfusion. PMID- 26900722 TI - The role of cardiac biochemical markers in aortic stenosis. AB - Calcified aortic stenosis is one of the most common causes of heart failure in the elderly. Current guidelines recommend aortic valve replacement in patients with severe disease and evidence of decompensation based on either symptoms or impaired systolic ejection fraction. However, symptoms are often subjective whilst impaired ejection fraction is not a sensitive marker of ventricular decompensation. Interest has surrounded the use of cardiac biochemical markers as objective measures of left ventricular decompensation in aortic stenosis. We will first examine mechanisms of release of biochemical markers associated with myocardial wall stress (BNP/NT-proBNP), myocardial fibrosis (markers of collagen metabolism, galectin-3, soluble ST2) and myocyte death/myocardial ischemia (high sensitivity cardiac troponins, heart-type fatty acid binding protein, myosin binding protein C); and discuss future directions of these markers. PMID- 26900721 TI - CHOP Contributes to, But Is Not the Only Mediator of, IAPP Induced beta-Cell Apoptosis. AB - The islet in type 2 diabetes is characterized by beta-cell loss, increased beta cell apoptosis, and islet amyloid derived from islet amyloid polypeptide (IAPP). When protein misfolding protective mechanisms are overcome, human IAPP (h-IAPP) forms membrane permeant toxic oligomers that induce beta-cell dysfunction and apoptosis. In humans with type 2 diabetes (T2D) and mice transgenic for h-IAPP, endoplasmic reticulum (ER) stress has been inferred from nuclear translocation of CCAAT/enhancer-binding protein homologous protein (CHOP), an established mediator of ER stress. To establish whether h-IAPP toxicity is mediated by ER stress, we evaluated diabetes onset and beta-cell mass in h-IAPP transgenic (h-TG) mice with and without deletion of CHOP in comparison with wild-type controls. Diabetes was delayed in h-TG CHOP(-/-) mice, with relatively preserved beta-cell mass and decreased beta-cell apoptosis. Deletion of CHOP attenuates dysfunction of the autophagy/lysosomal pathway in beta-cells of h-TG mice, uncovering a role for CHOP in mediating h-IAPP-induced dysfunction of autophagy. As deletion of CHOP delayed but did not prevent h-IAPP-induced beta-cell loss and diabetes, we examined CHOP-independent stress pathways. JNK, a target of the IRE-1pTRAF2 complex, and the Bcl-2 family proapoptotic mediator BIM, a target of ATF4, were comparably activated by h-IAPP expression in the presence and absence of CHOP. Therefore, although these studies affirm that CHOP is a mediator of h-IAPP induced ER stress, it is not the only one. Therefore, suppression of CHOP alone is unlikely to be a durable therapeutic strategy to protect against h-IAPP toxicity because multiple stress pathways are activated. PMID- 26900723 TI - 'Old and ill': death anxiety and coping strategies influencing health professionals' well-being and dementia care. AB - OBJECTIVES: This paper examined the psychological factors that influence the well being of health professionals who work with people with dementia and the types of care (person-centred or task-oriented) provided to these patients. METHODS: The literature was reviewed to identify the factors influencing the well-being of, and types of care provided by, health professionals working with people experiencing dementia. RESULTS: Based on our review of the literature, we propose that approaches to care and the well-being of health professionals working with dementia patients are influenced by the characterisation of dementia as a terminal illness that typically occurs in older people. Drawing upon terror management theory, we argue that exposure to dementia patients is likely to promote awareness of one's own mortality and death-related anxiety. A theoretical model is presented which posits that health professionals working in dementia care draw on experiential avoidance to manage this anxiety. Both death anxiety, and coping strategies, such as experiential avoidance, used to manage this anxiety may influence health professionals' approaches to care of, and attitudes towards, dementia patients. We also suggest a bi-directional relationship between health professionals' approaches to care and well-being. CONCLUSION: Recommendations are made regarding future directions for research and implications for training of health professionals providing direct service or consultation in dementia care. PMID- 26900725 TI - Immunomodulators for the treatment of Crohn's disease in adults: optimal use and prospects for future drug treatments. AB - Crohn's disease (CD) requires treatment beyond symptoms by enabling and maintaining mucosal healing and therefore clinical remission. However, with the increasing use of biologics there have been safety concerns and there is a significant cost implication with the early use of biologics. Therefore, it is imperative that patients with severe/complicated disease or poor prognostic factors are treated with an aggressive strategy while all remaining patients should be treated in a step-up strategy. The potential for disease modification with thiopurines and methotrexate is debated in CD when they are used as a monotherapy. In this review we discuss existing and newer therapies that have recently been developed for CD. We will also provide an algorithm for current management of adult CD patients in routine clinical practice. PMID- 26900724 TI - Psychiatric disease as a risk factor in fast-track hip and knee replacement. AB - Recent studies suggest that patients with psychiatric disorders tend to do worse than patients without a psychiatric diagnosis when undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA). Whether this is due to their psychiatric condition, pharmacological treatment, a combination of the two, or something else has not been thoroughly analyzed-and there are no internationally accepted guidelines for perioperative management of psychiatric patients. This overview summarizes our current knowledge on perioperative risks in patients with preoperative psychiatric disorders and the possible role of psychotropic drugs in the perioperative course. This will be useful when planning future strategies for improvement of surgical outcome following hip and knee arthroplasty. PMID- 26900726 TI - Physician support of HPV vaccination school-entry requirements. AB - School-entry requirements in the US have led to high coverage for several vaccines, but few states and jurisdictions have adopted these policies for human papillomavirus (HPV) vaccination. Because physicians play a key role in advocating for vaccination policies, we assessed physician support of requiring HPV vaccine for school entry and correlates of this support. Participants were a national sample of 775 physicians who provide primary care, including vaccines, to adolescents. Physicians completed an online survey in 2014 that assessed their support for school-entry requirements for HPV vaccination of 11 and 12 y olds. We used multivariable logistic regression to assess correlates of support for these requirements. The majority of physicians (74%) supported some form of school entry requirements, with or without opt-out provisions. When opt-out provisions were not specified, 47% agreed that laws requiring HPV vaccination for school attendance were a "good idea." Physicians more often agreed with requirements, without opt-out provisions, if they: had more years in practice (OR=1.49; 95% CI: 1.09-2.04), gave higher quality HPV vaccine recommendations (OR=2.06; 95% CI: 1.45-2.93), believed that having requirements for Tdap, but not HPV, vaccination undermined its importance (OR=3.33; 95% CI: 2.26-4.9), and believed HPV vaccination was as or more important than other adolescent vaccinations (OR=2.30; 95% CI: 1.65-3.18). In conclusion, we found that many physicians supported school entry requirements for HPV vaccination. More research is needed to investigate the extent to which opt-out provisions might weaken or strengthen physician support of HPV vaccination school-entry requirements. PMID- 26900727 TI - How ovarian transplantation works and how resting follicle recruitment occurs: a review of results reported from one center. AB - Ovarian freezing and transplantation has garnered increasing interest as a potential way of preserving fertility in cancer patients. This special report aims to identify the success rate of frozen compared with fresh ovarian cortex transplantation (in one single series from one center for the sake of consistency), as well as potentially provides insight into the mechanism behind ovarian follicle recruitment. A comparison of fresh versus frozen transplantation techniques is presented, highlighting the similarity and differences between the fresh and frozen transplantation procedures. Much of the literature is scattered case reports with different patient populations and different techniques. This represents an effort to simplify and popularize an approach that has yielded favorable results (all cases recovered ovulation and 75% had successful spontaneous pregnancy) in one single, disciplined study. PMID- 26900728 TI - Rotavirus vaccination in a Medicaid infant population from four US states: compliance, vaccination completion rate, and predictors of compliance. AB - A retrospective observational cohort study was conducted using Medicaid administrative claims data from four states in the United States (US) to analyze overall and state-specific compliance and completion rates for rotavirus (RV) vaccines. Compliance was based on an infant receiving the recommended number of doses each within the appropriate time frame, and completion was based on an infant receiving the recommended number of doses over a recommended time period. Compliance and completion were defined separately for RV vaccines by package insert (PI) and Advisory Committee on Immunization Practices (ACIP) guidelines. Infants born between 1 May 2008 and 31 October 2011 in Florida, 31 July 2012 in Iowa and Kansas, and 30 April 2013 in Mississippi, and continuously enrolled in Medicaid with medical and pharmacy benefits for >=8 months from birth were included. Study participants were assigned to cohorts based on type of RV vaccinations received within recommended vaccination windows. Using the PI guidelines, there were 658,219 eligible infants; 40% received no RV vaccines. The RV1 cohort had a significantly higher proportion of compliant infants compared to the RV5 cohort (54% vs. 25%; p <0.001). For infants initiating RV1, 55% completed both doses; for infants initiating RV5, 44% completed all three doses (p<0.001). Analysis by state and by ACIP guidelines yielded similar trends. Major predictors of compliance to RV vaccination were use of RV1 vaccine and DTaP vaccination completion. Increased awareness to the importance and timeliness of vaccination is needed. PMID- 26900730 TI - Fever and neutropenia hospital discharges in children with cancer: A 2012 update. AB - Fever and neutropenia (FN) is a common precipitant for hospitalization among children with cancer, but hospital utilization trends are not well described. This study describes national trends for hospital discharges for FN among children with cancer for the year 2012, compared with the authors' previous analysis from 2009. Data were analyzed from the Kids' Inpatient Database (KID), an all-payer US hospital database, for 2012. Pediatric patients with cancer who had a discharge for FN were identified using age <=19 years, urgent or emergent admit type, nontransferred, and a combination of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for fever and neutropenia. The authors evaluated factors associated with a "short length of stay" (SLOS). Sampling weights were used to permit national inferences. In 2012, children with cancer accounted for 1.8% of pediatric hospital discharges (n = 120,675), with 12.2% (n = 13,456) of cancer-related discharges meeting FN criteria. Two fifths of FN discharges had a SLOS, which accounted for $91 million (2015 US$) in hospital charges. The majority had no serious infections; most common infections were viral infection (9.6%) or upper respiratory infection (9.6%). Factors significantly associated with SLOS included having a diagnosis of ear infection (odds ratio [OR] = 1.54, 95% confidence interval [CI]: 1.16-2.03), soft tissue sarcoma (OR = 1.47, CI: 1.10-1.95), and Hodgkin lymphoma (OR = 1.51, CI: 1.09-2.10), as compared with not having those diagnoses. SLOS admissions continue to be rarely associated with serious infections, but contribute substantially to the burden of hospitalization for pediatric FN. Implementation of risk stratification schemas to identify patients who meet low-risk criteria may decrease financial burden. PMID- 26900731 TI - Newer patents in antimycotic therapy. AB - There has been a global upsurge in fungal infections due to rise in immunodeficiencies, debilitation and situations of violated anatomical barriers. The available antifungal repertoire has limited activity and is fraught with toxicity concerns. Drug resistance has also shown a rapid upward trend. This has resulted in increased treatment failures, mortality and health care costs. Novel effective and safe antimycotics are needed. Analogues of existing antifungal compounds and new molecules are being developed. New targets are being explored for their putative role in curtailing fungal infections. Newer antigens as vaccine candidates are being researched into. Focused efforts in this direction have yielded encouraging results. This review illuminates the various antifungal strategies which hold promise for the future. PMID- 26900729 TI - The homologous recombination component EEPD1 is required for genome stability in response to developmental stress of vertebrate embryogenesis. AB - Stressed replication forks can be conservatively repaired and restarted using homologous recombination (HR), initiated by nuclease cleavage of branched structures at stalled forks. We previously reported that the 5' nuclease EEPD1 is recruited to stressed replication forks, where it plays critical early roles in HR initiation by promoting fork cleavage and end resection. HR repair of stressed replication forks prevents their repair by non-homologous end-joining (NHEJ), which would cause genome instability. Rapid cell division during vertebrate embryonic development generates enormous pressure to maintain replication speed and accuracy. To determine the role of EEPD1 in maintaining replication fork integrity and genome stability during rapid cell division in embryonic development, we assessed the role of EEPD1 during zebrafish embryogenesis. We show here that when EEPD1 is depleted, zebrafish embryos fail to develop normally and have a marked increase in death rate. Zebrafish embryos depleted of EEPD1 are far more sensitive to replication stress caused by nucleotide depletion. We hypothesized that the HR defect with EEPD1 depletion would shift repair of stressed replication forks to unopposed NHEJ, causing chromosome abnormalities. Consistent with this, EEPD1 depletion results in nuclear defects including anaphase bridges and micronuclei in stressed zebrafish embryos, similar to BRCA1 deficiency. These results demonstrate that the newly characterized HR protein EEPD1 maintains genome stability during embryonic replication stress. These data also imply that the rapid cell cycle transit seen during embryonic development produces replication stress that requires HR to resolve. PMID- 26900732 TI - Biofouling community composition across a range of environmental conditions and geographical locations suitable for floating marine renewable energy generation. AB - Knowledge of biofouling typical of marine structures is essential for engineers to define appropriate loading criteria in addition to informing other stakeholders about the ecological implications of creating novel artificial environments. There is a lack of information regarding biofouling community composition (including weight and density characteristics) on floating structures associated with future marine renewable energy generation technologies. A network of navigation buoys were identified across a range of geographical areas, environmental conditions (tidal flow speed, temperature and salinity), and deployment durations suitable for future developments. Despite the perceived importance of environmental and temporal factors, geographical location explained the greatest proportion of the observed variation in community composition, emphasising the importance of considering geography when assessing the impact of biofouling on device functioning and associated ecology. The principal taxa associated with variation in biofouling community composition were mussels (Mytilus edulis), which were also important when determining loading criteria. PMID- 26900733 TI - Functional Neuroanatomy and Neurophysiology of Functional Neurological Disorders (Conversion Disorder). AB - Much is known regarding the physical characteristics, comorbid symptoms, psychological makeup, and neuropsychological performance of patients with functional neurological disorders (FNDs)/conversion disorders. Gross neurostructural deficits do not account for the patients' deficits or symptoms. This review describes the literature focusing on potential neurobiological (i.e. functional neuroanatomic/neurophysiological) findings among individuals with FND, examining neuroimaging and neurophysiological studies of patients with the various forms of motor and sensory FND. In summary, neural networks and neurophysiologic mechanisms may mediate "functional" symptoms, reflecting neurobiological and intrapsychic processes. PMID- 26900734 TI - The Dialectic Between Empathy and Violence: An Opportunity for Intervention? AB - The authors provide a comprehensive review of the neurobiology of empathy and compare this with the neurobiology of psychopathic predatory violence-the most extreme deficit of empathy. This suggests that the specific areas of the prefrontal cortex and limbic system, which have been associated with violent behavior, also appear to subserve the capacity for empathy. Damage to these regions may result in the emergence of aggression, but not of empathy, suggesting a structurally inverse relationship between the two. The authors examine the evidence for a dialectic between empathy and predatory violence and explore the implications for early interventions with empathy training in treatment-resistant psychopathy. PMID- 26900735 TI - Quantifying Poststroke Apathy With Actimeters. AB - The authors tested the hypothesis that wrist-worn actimeters can quantify the severity of poststroke apathy. The authors studied 57 patients admitted to an acute rehabilitation unit for ischemic or hemorrhagic stroke. After accounting for motor deficit of the affected arm and accounting for age, each increment of the Apathy Inventory score correlated with 5.6 fewer minutes of moving per hour. The overall statistical model had an R(2) of only 0.34, suggesting unexplained factors for total movement time. Wrist-worn actimeters may serve as an objective, quantifiable measure of poststroke apathy in patients with an intact upper extremity but cannot be used alone to diagnose apathy. PMID- 26900736 TI - Exploring the Structural Relationship Between Interviewer and Self-Rated Affective Symptoms in Huntington's Disease. AB - This study explores the structural relationship between self-report and interview measures of affect in Huntington's disease. The findings suggest continued use of both to recognize the multidimensionality within a single common consideration of distress. PMID- 26900737 TI - Pathological Joking or Witzelsucht Revisited. AB - Humor, or the perception or elicitation of mirth and funniness, is distinguishable from laughter and can be differentially disturbed by neuropsychiatric disease. The authors describe two patients with constant joking, or Witzelsucht, in the absence of pseudobulbar affect and review the literature on pathological humor. These patients had involvement of frontal structures, impaired appreciation of nonsimple humor, and a compulsion for disinhibited joking. Current neuroscience suggests that impaired humor integration from right lateral frontal injury and disinhibition from orbitofrontal damage results in disinhibited humor, preferentially activating limbic and subcortical reward centers. Additional frontal-subcortical circuit dysfunction may promote pathological joking as a compulsion. PMID- 26900739 TI - Psychiatric Symptoms in the Initial Motor Stage of Parkinson's Disease. AB - Neuropsychiatric symptoms (NPS) are common in Parkinson's disease (PD). The aim of this study was to estimate the correlates of NPS in patients with PD in the initial motor stage of the disease (hemiparkinsonism). A total of 111 patients with PD and 105 healthy control participants were assessed. Patients with PD experienced apathy, depression, and anxiety more frequently compared with healthy controls. Sleep disturbances occurred commonly in early PD patients. Patients with PD and mild cognitive impairment (MCI) had depression and anxiety more frequently, but not apathy, compared with patients with PD without MCI. The results of this study confirm a high burden of NPS even in the earliest motor stage of PD. PMID- 26900740 TI - Lesion-Related Delusional Misidentification Syndromes: A Comprehensive Review of Reported Cases. AB - Delusional misidentification syndromes (DMSs) are persistent delusions of hyper- or hypofamiliarity for meaningful persons and places in one's environment. This study set to determine the clinical course, neuroanatomical localization, neuropsychological abnormalities, and delusional content in patients with DMSs occurring after focal neurological injuries. Sixty-one patients were identified: 28 with hypofamiliar delusions, 27 with hyperfamiliar delusions, and, most surprisingly, six patients with both hypo- and hyperfamiliar delusions. Recognition is often delayed by months from the time of injury, and the delusions are self-limited. Patients with DMSs had right hemisphere (92%) injuries (specifically right frontal injuries in 63%), prominent memory impairment (73%), and multiple concurrent DMSs (29%). PMID- 26900738 TI - Apathy Is Associated With Ventral Striatum Volume in Schizophrenia Spectrum Disorder. AB - Apathy is prevalent in schizophrenia, but its etiology has received little investigation. The ventral striatum (VS), a key brain region involved in motivated behavior, has been implicated in studies of apathy. We therefore evaluated whether apathy is associated with volume of the VS on MRI in 23 patients with schizophrenia using voxel-based morphometry. Results indicated that greater self-reported apathy severity was associated with smaller volume of the right VS even when controlling for age, gender, depression, and total gray matter volume. The finding suggests that apathy is related to abnormality of brain circuitry subserving motivated behavior in patients with schizophrenia. PMID- 26900741 TI - CORRELATION OF OPTICAL COHERENCE TOMOGRAPHIC HYPERREFLECTIVE FOCI WITH VISUAL OUTCOMES IN DIFFERENT PATTERNS OF DIABETIC MACULAR EDEMA. AB - PURPOSE: To investigate the correlation between the hyperreflective foci (HF) on spectral domain optical coherence tomography at the baseline and visual outcomes after intravitreal bevacizumab injections in different patterns of diabetic macular edema. METHODS: We retrospectively reviewed the medical records of 97 eyes (80 patients) with diabetic macular edema that were treated with intravitreal bevacizumab injection. The eyes were categorized into three groups by optical coherence tomographic features: diffuse retinal thickening, cystoid macular edema, and serous retinal detachment. The baseline and final best corrected visual acuity, foveal thickness, the number of HF, and status of the external limiting membrane and the ellipsoid zone were evaluated and compared among the three groups. RESULTS: The number of HF in all retinal layers was reduced in patients with diabetic macular edema after treatment. In multivariate regression analysis, the final visual acuity was associated with baseline visual acuity (P = 0.004) and number of outer retinal HF (P = 0.004) in the diffuse retinal thickening group, baseline visual acuity (P = 0.002) and number of outer retinal HF (P < 0.001) in the cystoid macular edema group, and baseline number of inner and outer retinal HF (P = 0.041, P = 0.025, respectively) in the serous retinal detachment group. The baseline number of the outer retinal HF was correlated with the final visual acuity, ellipsoid zone disruption length, and external limiting membrane disruption length in all three groups. CONCLUSION: The number of HF in outer retinal layer on spectral domain optical coherence tomography at baseline might predict the final visual acuity in all three patterns of diabetic macular edema groups. PMID- 26900742 TI - En Face Optical Coherence Tomography of Bilateral Myopic Macular Retinoschisis. PMID- 26900743 TI - Correspondence. PMID- 26900744 TI - Reply. PMID- 26900746 TI - Application of Reverse Engineering Template for the Correction of Asymmetric Deformity of Maxillofacial Fibrous Dysplasia. AB - Facial asymmetry deformity is the most common symptom of patients with fibrous dysplasia. This study provides a novel method based on computed tomography scan data, mirror-imaged reverse engineering and rapid prototyping for design and manufacture of an individual template guiding accurately the extent and quantity of partial resection of hyperplastic tissues to reshape the affected bones during operation. Ten adult patients with unilateral facial fibrous dysplasia accepted these treatments, the postoperative appearances showed that the protrusions were effectively reduced; bilateral faces were basically symmetric with no serious complications. This method shorts operation time, decreases surgical risk, and guarantees the aesthetic symmetry. Apparent recurrence was not observed during the follow-up period, and the final outcomes were satisfactory for both surgeons and patients. PMID- 26900745 TI - MRI postprocessing in presurgical evaluation. AB - PURPOSE OF REVIEW: Advanced MRI postprocessing techniques are increasingly used to complement visual analysis and elucidate structural epileptogenic lesions. This review summarizes recent developments in MRI postprocessing in the context of epilepsy presurgical evaluation, with the focus on patients with unremarkable MRI by visual analysis (i.e. 'nonlesional' MRI). RECENT FINDINGS: Various methods of MRI postprocessing have been reported to show additional clinical values in the following areas: lesion detection on an individual level; lesion confirmation for reducing the risk of over reading the MRI; detection of sulcal/gyral morphologic changes that are particularly difficult for visual analysis; and delineation of cortical abnormalities extending beyond the visible lesion. Future directions to improve the performance of MRI postprocessing include using higher magnetic field strength for better signal-to-noise ratio and contrast-to-noise ratio adopting a multicontrast frame work and integration with other noninvasive modalities. SUMMARY: MRI postprocessing can provide essential value to increase the yield of structural MRI and should be included as part of the presurgical evaluation of nonlesional epilepsies. MRI postprocessing allows for more accurate identification/delineation of cortical abnormalities, which should then be more confidently targeted and mapped. PMID- 26900747 TI - Reconstruction of Extended Orbitomaxillectomy and Hemimandibulectomy Defects With Fibula Flaps and Patient-Specific Implants. AB - An extended orbitomaxillectomy and hemimandibulectomy for polyostotic juvenile ossifying fibroma resection were performed with the assistance of patient specific cutting guides. The resulting defects were reconstructed in stages. First, a patient-specific mandibular reconstruction plate was fixed to the hemimandibulectomy defect in the same operation as the resection. After margins were proven to be free of tumor on histologic analysis, a free fibula flap contoured to the reconstruction plate was used to reconstruct the mandible. Reconstruction of the maxilla, alveolus, and orbit were performed with a second free fibula flap and patient-specific implants. The lining of the total nasal vault cavity was reconstructed with septal flaps. At 7 months postoperatively, the patient had an excellent esthetic result and resolved diplopia. PMID- 26900748 TI - One-step continuous synthesis of functionalized magnetite nanoflowers. AB - For the first time, functionalized magnetite nanoparticles (Fe3O4 NPs) that form aggregates with a nanoflower morphology were synthesized using a rapid (11 s) one step continuous hydrothermal process, which was recently modified, and their application as a T 2 magnetic resonance imaging (MRI) contrast agent was evaluated. The nanoparticles functionalized with 3,4-dihydroxy-L-phenylalanine (LDOPA) or 3,4-dihydroxyhydrocinnamic acid (DHCA) consisted of small crystallites of approximately 15 nm of diameter that assembled to form flower-shaped aggregate structures. The Fe3O4-LDOPA nanoflowers exhibited a high transverse relaxivity, r 2 of 418 +/- 10 l mmolFe (-1) s(-1) at 3 T owing to magnetic dipolar interactions, which is twice as that of the commercial Feridex(r)/Endorem(r). The prepared nanostructures were compared with bare Fe3O4 NPs and citrated Fe3O4 NPs. DHCA, LDOPA, and citric acid (CA) were found to have an anti-oxidizing effect and to influence the crystallite size and the lattice parameter of the NPs. DHCA and LDOPA increased the crystallite size, whereas CA decreased it. Surface modification increased the colloidal stability of NPs as compared to bare NPs. Nanoflower suspensions of Fe3O4-LDOPA NPs were found to be stable in the phosphate-buffered saline, saline medium, and minimal essential medium and formed aggregates of sizes smaller than 120 nm. All samples were found to be superparamagnetic in nature and the highest saturation magnetization was obtained for the Fe3O4-LDOPA samples. These NPs can bind to polymers such as PEG, and to fluorescent and chelating agents owing to the presence of free -NH2 or -COOH groups on the surface of NPs, allowing their use in dual imaging applications. PMID- 26900749 TI - Bartonella Species Identified in Rodent and Feline Hosts from Island and Mainland Western Australia. AB - Bacteria of the genus Bartonella have been described in multiple mammalian hosts with many species capable of causing disease in humans. Cats and various species of rats have been reported to play a role as vertebrate hosts to a number of Bartonella spp. This study aimed to identify Bartonella spp. in Western Australia, Dirk Hartog Island (DHI), and Christmas Island (CI) and to investigate the presence of potential arthropod vectors. Feral cats were collected from CI (n = 35), DHI (n = 23) and southwest Western Australia (swWA; n = 58), and black rats were collected from CI (n = 48). Individuals were necropsied, ectoparasites were collected by external examination of carcasses, and splenic tissue was collected for polymerase chain reaction analysis to detect Bartonella DNA. Bartonella henselae DNA was detected from two cats and Bartonella koehlerae DNA from one cat in southwest WA, but Bartonella DNA was not identified in cats on DHI or CI. Bartonella phoceensis (28/48 = 58.3%) and a novel Bartonella genotype (8/48 = 16.7%) based on the internal transcribed space region were detected in the spleens of black rats on CI. Detection of Bartonella spp. in each location corresponded to the presence of ectoparasites. Cats from southwest WA harbored four species of fleas, including Ctenocephalides felis, and black rats on CI were infested with multiple species of ectoparasites, including mites, fleas, and lice. Conversely, cats on Dirk Hartog and CI were free of ectoparasites. This study has identified the DNA of Bartonella species from island and mainland swWA with some (B. henselae and B. koehlerae) of known zoonotic importance. This study further extends the geographical range for the pathogenic B. koehlerae. The association of Bartonella with ectoparasites is unsurprising, but little is known about the specific vector competence of the ectoparasites identified in this study. PMID- 26900750 TI - Physical Activity Coparticipation and Independent Mobility as Correlates of Objectively Measured Nonschool Physical Activity in Different School Grades. The UP&DOWN Study. AB - BACKGROUND: The aim was to investigate the association of (i) parental, sibling, and friend coparticipation in physical activity (PA); and (ii) independent mobility (IM) for walking, cycling, and taking public transport with objectively measured nonschool PA on week- and weekend days in different school grades. METHODS: A total of 1376 Spanish youngsters (50.8% boys; mean age 11.96 +/- 2.48 years) participated in the study. Participants reported the frequency of their parental, sibling, and best friend coparticipation in PA with them and their IM for walking, cycling, and taking public transport. PA was objectively measured by accelerometry. RESULTS: Coparticipation in PA and IM were more frequently related to nonschool PA among adolescents than among children. Friend coparticipation in PA was positively associated with higher levels of nonschool PA in adolescents. IM for walking and IM for cycling in adolescents were related to nonschool PA on weekdays. CONCLUSIONS: Our results highlight the need for age-focused interventions and the integration of family and friends to promote PA in youth. PMID- 26900753 TI - Reversible Nanoparticle Cubic Lattices in Blue Phase Liquid Crystals. AB - Blue phases (BPs), a distinct class of liquid crystals (LCs) with 3D periodic ordering of double twist cylinders involving orthogonal helical director twists, have been theoretically studied as potential templates for tunable colloidal crystals. Here, we report the spontaneous formation of thermally reversible, cubic crystal nanoparticle (NP) assemblies in BPs. Gold NPs, functionalized to be highly miscible in cyanobiphenyl-based LCs, were dispersed in BP mixtures and characterized by polarized optical microscopy and synchrotron small-angle X-ray scattering (SAXS). The NPs assemble by selectively migrating to periodic strong trapping sites in the BP disclination lines. The NP lattice, remarkably robust given the small particle size (4.5 nm diameter), is commensurate with that of the BP matrix. At the BP I to BP II phase transition, the NP lattice reversibly switches between two different cubic structures. The simultaneous presence of two different symmetries in a single material presents an interesting opportunity to develop novel dynamic optical materials. PMID- 26900751 TI - CHIP controls necroptosis through ubiquitylation- and lysosome-dependent degradation of RIPK3. AB - Receptor-interacting protein kinase 3 (RIPK3) functions as a key regulator of necroptosis. Here, we report that the RIPK3 expression level is negatively regulated by CHIP (carboxyl terminus of Hsp70-interacting protein; also known as STUB1) E3 ligase-mediated ubiquitylation. Chip(-/-) mouse embryonic fibroblasts and CHIP-depleted L929 and HT-29 cells exhibited higher levels of RIPK3 expression, resulting in increased sensitivity to necroptosis induced by TNF (also known as TNFalpha). These phenomena are due to the CHIP-mediated ubiquitylation of RIPK3, which leads to its lysosomal degradation. Interestingly, RIPK1 expression is also negatively regulated by CHIP-mediated ubiquitylation, validating the major role of CHIP in necrosome formation and sensitivity to TNF mediated necroptosis. Chip(-/-) mice (C57BL/6) exhibit inflammation in the thymus and massive cell death and disintegration in the small intestinal tract, and die within a few weeks after birth. These phenotypes are rescued by crossing with Ripk3(-/-) mice. These results imply that CHIP is a bona fide negative regulator of the RIPK1-RIPK3 necrosome formation leading to desensitization of TNF-mediated necroptosis. PMID- 26900754 TI - Scanning probe microscopy and spectroscopy of colloidal semiconductor nanocrystals and assembled structures. AB - Colloidal semiconductor nanocrystals become increasingly important in materials science and technology, due to their optoelectronic properties that are tunable by size. The measurement and understanding of their energy levels is key to scientific and technological progress. Here we review how the confined electronic orbitals and related energy levels of individual semiconductor quantum dots have been measured by means of scanning tunneling microscopy and spectroscopy. These techniques were originally developed for flat conducting surfaces, but they have been adapted to investigate the atomic and electronic structure of semiconductor quantum dots. We compare the results obtained on colloidal quantum dots with those on comparable solid-state ones. We also compare the results obtained with scanning tunneling spectroscopy with those of optical spectroscopy. The first three sections provide an introduction to colloidal quantum dots, and a theoretical basis to be able to understand tunneling spectroscopy on dots attached to a conducting surface. In sections 4 and 5 , we review the work performed on lead-chalcogenide nanocrystals and on colloidal quantum dots and rods of II-VI compounds, respectively. In section 6 , we deal with colloidal III V nanocrystals and compare the results with their self-assembled counter parts. In section 7 , we review the work on other types of semiconductor quantum dots, especially on Si and Ge nanocrystals. PMID- 26900752 TI - Dicer1-miR-328-Bace1 signalling controls brown adipose tissue differentiation and function. AB - Activation of brown adipose tissue (BAT) controls energy homeostasis in rodents and humans and has emerged as an innovative strategy for the treatment of obesity and type 2 diabetes mellitus. Here we show that ageing- and obesity-associated dysfunction of brown fat coincides with global microRNA downregulation due to reduced expression of the microRNA-processing node Dicer1. Consequently, heterozygosity of Dicer1 in BAT aggravated diet-induced-obesity (DIO)-evoked deterioration of glucose metabolism. Analyses of differential microRNA expression during preadipocyte commitment and mouse models of progeria, longevity and DIO identified miR-328 as a regulator of BAT differentiation. Reducing miR-328 blocked preadipocyte commitment, whereas miR-328 overexpression instigated BAT differentiation and impaired muscle progenitor commitment-partly through silencing of the beta-secretase Bace1. Loss of Bace1 enhanced brown preadipocyte specification in vitro and was overexpressed in BAT of obese and progeroid mice. In vivo Bace1 inhibition delayed DIO-induced weight gain and improved glucose tolerance and insulin sensitivity. These experiments reveal Dicer1-miR-328-Bace1 signalling as a determinant of BAT function, and highlight the potential of Bace1 inhibition as a therapeutic approach to improve not only neurodegenerative diseases but also ageing- and obesity-associated impairments of BAT function. PMID- 26900755 TI - Sensitivity and specificity of human brain glutathione concentrations measured using short-TE (1)H MRS at 7 T. AB - Although the MR editing techniques that have traditionally been used for the measurement of glutathione (GSH) concentrations in vivo address the problem of spectral overlap, they suffer detriments associated with inherently long TEs. The purpose of this study was to characterize the sensitivity and specificity for the quantification of GSH concentrations without editing at short TE. The approach was to measure synthetically generated changes in GSH concentrations from in vivo stimulated echo acquisition mode (STEAM) spectra after in vitro GSH spectra had been added to or subtracted from them. Spectra from five test subjects were synthetically altered to mimic changes in the GSH signal. To account for different background noise between measurements, retest spectra (from the same individuals as used to generate the altered data) and spectra from five other individuals were compared with the synthetically altered spectra to investigate the reliability of the quantification of GSH concentration. Using STEAM spectroscopy at 7 T, GSH concentration differences on the order of 20% were detected between test and retest studies, as well as between differing populations in a small sample (n = 5) with high accuracy (R(2) > 0.99) and certainty (p <= 0.01). Both increases and decreases in GSH concentration were reliably quantified with small impact on the quantification of ascorbate and gamma-aminobutyric acid. These results show the feasibility of using short-TE (1)H MRS to measure biologically relevant changes and differences in human brain GSH concentration. Although these outcomes are specific to the experimental approach used and the spectral quality achieved, this study serves as a template for the analogous scrutiny of quantification reliability for other compounds, methodologies and spectral qualities. PMID- 26900756 TI - Chiral atomically thin films. AB - Chiral materials possess left- and right-handed counterparts linked by mirror symmetry. These materials are useful for advanced applications in polarization optics, stereochemistry and spintronics. In particular, the realization of spatially uniform chiral films with atomic-scale control of their handedness could provide a powerful means for developing nanodevices with novel chiral properties. However, previous approaches based on natural or grown films, or arrays of fabricated building blocks, could not offer a direct means to program intrinsic chiral properties of the film on the atomic scale. Here, we report a chiral stacking approach, where two-dimensional materials are positioned layer-by layer with precise control of the interlayer rotation (theta) and polarity, resulting in tunable chiral properties of the final stack. Using this method, we produce left- and right-handed bilayer graphene, that is, a two-atom-thick chiral film. The film displays one of the highest intrinsic ellipticity values (6.5 deg MUm(-1)) ever reported, and a remarkably strong circular dichroism (CD) with the peak energy and sign tuned by theta and polarity. We show that these chiral properties originate from the large in-plane magnetic moment associated with the interlayer optical transition. Furthermore, we show that we can program the chiral properties of atomically thin films layer-by-layer by producing three layer graphene films with structurally controlled CD spectra. PMID- 26900757 TI - Physically unclonable cryptographic primitives using self-assembled carbon nanotubes. AB - Information security underpins many aspects of modern society. However, silicon chips are vulnerable to hazards such as counterfeiting, tampering and information leakage through side-channel attacks (for example, by measuring power consumption, timing or electromagnetic radiation). Single-walled carbon nanotubes are a potential replacement for silicon as the channel material of transistors due to their superb electrical properties and intrinsic ultrathin body, but problems such as limited semiconducting purity and non-ideal assembly still need to be addressed before they can deliver high-performance electronics. Here, we show that by using these inherent imperfections, an unclonable electronic random structure can be constructed at low cost from carbon nanotubes. The nanotubes are self-assembled into patterned HfO2 trenches using ion-exchange chemistry, and the width of the trench is optimized to maximize the randomness of the nanotube placement. With this approach, two-dimensional (2D) random bit arrays are created that can offer ternary-bit architecture by determining the connection yield and switching type of the nanotube devices. As a result, our cryptographic keys provide a significantly higher level of security than conventional binary-bit architecture with the same key size. PMID- 26900758 TI - Inhibitory Effect of Imiquimod-Induced Psoriasis-Like Skin Inflammation in Mice by Histamine H4 Receptor Agonist 4-Methylhistamine. AB - Psoriasis is a chronic inflammatory immune-mediated autoimmune skin disorder. The histamine H4 receptor (H4R) agonist 4-methylhistamine (4-MH) plays an important role in immunomodulation of inflammatory responses associated with allergic inflammatory diseases. In this study, we investigated the effects of H4R agonist 4-MH on the development of imiquimod (IMQ)-induced psoriasis-like skin inflammation in mice and explored the immunoregulatory mechanism involved. The total clinical severity scores were significantly ameliorated by treatment with 4 MH (20 mg/kg) and 4-MH (40 mg/kg). Histological analysis of the skin revealed that 4-MH (20 mg/kg) and 4-MH (40 mg/kg) significantly attenuated the psoriatic phenotypes, including epidermal hyperplasis, hyperkeratosis and lymphocytes infiltration. Treatment with 4-MH (20 mg/kg) and 4-MH (40 mg/kg) led to reductions in the levels of Th1 cytokines (TNF-alpha, IFN-alpha, and IL-27) in the serum and dorsal skin, whereas Th17 cytokines levels (IL-17A and IL-23) did not change in response to treatment with 4-MH (20 mg/kg) and 4-MH (40 mg/kg). Furthermore, the number of CD4(+) CD25(+) FoxP3(+) regulatory T (Treg) cells was significantly increased by treatment with 4-MH (40 mg/kg). Taken together, these results imply that H4R agonist 4-MH might be an effective immunomodulatory approach for treatment of patients with psoriasis and the effects may be related to inhibited epidermal alteration, selectively reduced Th1 pro-inflammatory cytokines, and recruited CD4(+) CD25(+) FoxP3(+) Treg cells. PMID- 26900760 TI - A Comparative Study of Cellular Uptake and Subcellular Localization of Doxorubicin Loaded in Self-Assemblies of Amphiphilic Copolymers with Pendant Dendron by MDA-MB-231 Human Breast Cancer Cells. AB - Previously synthesized amphiphilic diblock copolymers with pendant dendron moieties have been investigated for their potential use as drug carriers to improve the delivery of an anticancer drug to human breast cancer cells. Diblock copolymer (P71 D3 )-based micelles effectively encapsulate the doxorubicin (DOX) with a high drug-loading capacity (~95%, 104 DOX molecules per micelle), which is approximately double the amount of drug loaded into the diblock copolymer (P296 D1 ) vesicles. DOX released from the resultant P71 D3 /DOX micelles is approximately 1.3-fold more abundant, at a tumoral acidic pH of 5.5 compared with a pH of 7.4. The P71 D3 /DOX micelles also enhance drug potency in breast cancer MDA-MB-231 cells due to their higher intracellular uptake, by approximately twofold, compared with the vesicular nanocarrier, and free DOX. Micellar nanocarriers are taken up by lysosomes via energy-dependent processes, followed by the release of DOX into the cytoplasm and subsequent translocation into the nucleus, where it exert its cytotoxic effect. PMID- 26900761 TI - Feeling Nature's PAINS: Natural Products, Natural Product Drugs, and Pan Assay Interference Compounds (PAINS). AB - We have previously reported on classes of compounds that can interfere with bioassays via a number of different mechanisms and termed such compounds Pan Assay INterference compoundS, or PAINS. These compounds were defined on the basis of high-throughput data derived from vendor-supplied synthetics. The question therefore arises whether the concept of PAINS is relevant to compounds of natural origin. Here, it is shown that this is indeed the case, but that the context of the biological readout is an important factor that must be brought into consideration. PMID- 26900759 TI - On-resonance variable delay multipulse scheme for imaging of fast-exchanging protons and semisolid macromolecules. AB - PURPOSE: To develop an on-resonance variable delay multipulse (VDMP) scheme to image magnetization transfer contrast (MTC) and the chemical exchange saturation transfer (CEST) contrast of total fast-exchanging protons (TFP) with exchange rate above approximately 1 kHz. METHODS: A train of high power binomial pulses was applied at the water resonance. The interpulse delay, called mixing time, was varied to observe its effect on the water signal reduction, allowing separation and quantification of MTC and CEST contributions as a result of their different proton transfer rates. The fast-exchanging protons in CEST and MTC are labeled together with the short T2 components in MTC and separated out using a variable mixing time. RESULTS: Phantom studies of selected metabolite solutions (glucose, glutamate, creatine, myo-inositol), bovine serum albumin (BSA), and hair conditioner show the capability of on-resonance VDMP to separate out exchangeable protons with exchange rates above 1 kHz. Quantitative MTC and TFP maps were acquired on healthy mouse brains using this method, showing strong gray/white matter contrast for the slowly transferring MTC protons, whereas the TFP map was more uniform across the brain but somewhat higher in gray matter. CONCLUSIONS: The new method provides a simple way of imaging fast-exchanging protons and MTC components with a slow transfer rate. Magn Reson Med 77:730-739, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 26900762 TI - Comparison of lidocaine, levobupivacaine or ropivacaine for distal paravertebral thoracolumbar anesthesia in ewes. AB - OBJECTIVE: To compare the effects of lidocaine, levobupivacaine, or ropivacaine on the onset time and duration of anesthesia of the flank of ewes, using the distal paravertebral thoracolumbar approach. STUDY DESIGN: Randomized experimental study. ANIMALS: Twenty-six healthy mixed-breed ewes (46 +/- 3.1 kg). METHODS: Thoracolumbar paravertebral nerve blocks were performed using the distal approach in sheep for ruminal fistulation. The 13th thoracic (T13), first lumbar (L1) and second lumbar (L2) nerves were infiltrated with 2% lidocaine (group GLI, n = 9), 0.5% levobupivacaine (group GLE, n = 8) or 0.5% ropivacaine (group GRO, n = 9); 1.5 mL on the dorsal branch and 2.5 mL on the ventral branch, total volume of 12 mL per ewe. Anesthesia onset time and duration were assessed by application of superficial and deep pin pricks, and skin clamping with a hemostat. Heart rate, respiratory rate, rectal temperature and systemic arterial pressures were recorded prior to nerve block (T0), after the anesthetic agent injection and onset time (T1) and predetermined time points during the surgical procedure (T2 T6). RESULTS: Incomplete nerve blocks were present in five of the 26 ewes enrolled in the study and they were not included in the statistical analyzes. Onset times in GLI, GLE and GRO were 1.5 +/- 0.5, 3.1 +/- 1.5 and 2.1 +/- 0.8 minutes, respectively, with GLE significantly longer than GLI. The durations of anesthesia for GLI, GLE and GRO were 80 +/- 27, 649 +/- 68 and 590 +/- 40 minutes, respectively, with the duration of GLI significantly shorter than GLE and GRO. There were no clinically important changes in cardiopulmonary variables. CONCLUSION AND CLINICAL RELEVANCE: Administration of levobupivacaine and ropivacaine at the distal paravertebral site to block nerves T13, L1 and L2 produced a longer duration of anesthesia of the ewe's flanks compared with lidocaine. PMID- 26900763 TI - Performance Improvement of Polymer Solar Cells by Surface-Energy-Induced Dual Plasmon Resonance. AB - The surface plasmon resonance (SPR) effect of metal nanoparticles (MNPs) is effectively applied on polymer solar cells (PSCs) to improve power conversion efficiency (PCE). However, universality of the reported results mainly focused on utilizing single type of MNPs to enhance light absorption only in specific narrow wavelength range. Herein, a surface-energy-induced dual MNP plasmon resonance by thermally evaporating method was presented to achieve the absorption enhancement in wider range. The differences of surface energy between silver (Ag), gold (Au), and tungsten trioxide (WO3) compared by contact angle images enable Ag and Au prefer to respectively aggregate into isolated islands rather than films at the initial stage of the evaporation process, which was clearly demonstrated in the atomic force microscopy (AFM) measurement. The sum of plasmon-enhanced wavelength range induced by both Ag NPs (350-450 nm) and Au NPs (450-600 nm) almost cover the whole absorption spectra of active layers, which compatibly contribute a significant efficiency improvement from 4.57 +/- 0.16 to 6.55 +/- 0.12% compared to the one without MNPs. Besides, steady state photoluminescence (PL) measurements provide strong evidence that the SPR induced by the Ag-Au NPs increase the intensity of light absorption. Finally, ultraviolet photoelectron spectroscopy (UPS) reveals that doping Au and Ag causes upper shift of both the work function and valence band of WO3, which is directly related to hole collection ability. We believe the surface-energy-induced dual plasmon resonance enhancement by simple thermally evaporating technique might pave the way toward higher-efficiency PSCs. PMID- 26900764 TI - Field-Induced Slow Magnetic Relaxation in the Ni(I) Complexes [NiCl(PPh3)2].C4H8O and [Ni(N(SiMe3)2)(PPh3)2]. AB - Direct current (dc) and alternating current (ac) magnetic measurements have been performed on the three Ni(I) complexes: [NiCl(PPh3)3], [NiCl(PPh3)2].C4H8O, and [Ni(N(SiMe3)2)(PPh3)2]. Fits of the dc magnetic data suggest an almost similar behavior of the three compounds, which display only moderate deviations from the spin-only values. The ac magnetic investigations reveal that the two complexes with trigonal planar coordination--[NiCl(PPh3)2].C4H8O and [Ni(N(SiMe3)2)(PPh3)2] -display slow magnetic relaxation at low temperatures under applied dc fields, whereas tetrahedral [NiCl(PPh3)3] does not. Ground and excited states as well as magnetic data were calculated by ab initio wave function based multi configurational methods, including dynamic correlation as well as spin-orbit coupling. The two trigonal planar complexes comprise well-isolated S = (1)/2 ground states, whereas two S = (1)/2 states with a splitting of less than 100 cm( 1) were found in the tetrahedral compound. PMID- 26900765 TI - Apical access and closure devices for transapical transcatheter heart valve procedures. AB - The majority of transcatheter aortic valve implantations, structural heart procedures and the newly developed transcatheter mitral valve repair and replacement are traditionally performed either through a transfemoral or a transapical access site, depending on the presence of severe peripheral vascular disease or anatomic limitations. The transapical approach, which carries specific advantages related to its antegrade nature and the short distance between the introduction site and the cardiac target, is traditionally performed through a left anterolateral mini-thoracotomy and requires rib retractors, soft tissue retractors and reinforced apical sutures to secure, at first, the left ventricular apex for the introduction of the stent-valve delivery systems and then to seal the access site at the end of the procedure. However, despite the advent of low-profile apical sheaths and newly designed delivery systems, the apical approach represents a challenge for the surgeon, as it has the risk of apical tear, life-threatening apical bleeding, myocardial damage, coronary damage and infections. Last but not least, the use of large-calibre stent-valve delivery systems and devices through standard mini-thoracotomies compromises any attempt to perform transapical transcatheter structural heart procedures entirely percutaneously, as happens with the transfemoral access site, or via a thoracoscopic or a miniaturised video-assisted percutaneous technique. During the past few years, prototypes of apical access and closure devices for transapical heart valve procedures have been developed and tested to make this standardised successful procedure easier. Some of them represent an important step towards the development of truly percutaneous transcatheter transapical heart valve procedures in the clinical setting. PMID- 26900766 TI - Increment in Drug Loading on an Antibody-Drug Conjugate Increases Its Binding to the Human Neonatal Fc Receptor in Vitro. AB - Antibody-drug conjugates, such as brentuximab vedotin (BTXv), are an innovative category of monoclonal antibodies. BTXv is bioconjugated via the chemical reduction of cysteine residues involved in disulfide bonds. Species of BTXv containing zero, two, four, six, or eight vedotin molecules per antibody coexist in the stock solution. We investigated the influence of drug loading on the binding of the antibody to FcRn, a major determinant of antibody pharmacokinetics in humans. We developed a hydrophobic interaction chromatography (HIC) method for separating the different species present in the stock solution of BTXv, and we purified and characterized the collected species before use. We assessed the binding of these different species to FcRn in a cellular assay based on flow cytometry and surface plasmon resonance. HIC separated the different species of BTXv and allowed their collection at adequate levels of purity. Physicochemical characterization showed that species with higher levels of drug loading tended to form more aggregates. FcRn binding assays showed that the most conjugated species, particularly those with saturated loading, interacted more strongly than unconjugated BTXv with the FcRn. PMID- 26900767 TI - Glycogenic hepatopathy in young adults: a case series. AB - Glycogenic hepatopathy is a rare and under-recognized complication in long standing poorly controlled type 1 diabetes mellitus patients. This is a distinct entity from other causes of hepatomegaly and elevated liver enzymes in diabetics, such as nonalcoholic fatty liver disease. Glycogenic hepatopathy is characterized by the combination of poorly controlled diabetes, acute liver injury with marked elevation in serum aminotransferases, and the characteristic histological features on liver biopsy. It is important to distinguish this entity as it has the potential for resolution following improved glycemic control. In this report, we describe four cases of adult patients presenting elevated serum transaminases and hepatomegaly with a history of poorly controlled type I diabetes mellitus. One of the patients had also elevated amylase and lipase in the serum, without clinical or imagiologic evidence of acute pancreatitis (AP). Liver biopsy was performed in all patients and revealed glycogenic hepatopathy. Clinician's awareness of glycogenic hepatopathy should prevent diagnostic delay or misdiagnosis and will provide better insight and management for this condition. PMID- 26900768 TI - Application of an Integrated GPCR SAR-Modeling Platform To Explain the Activation Selectivity of Human 5-HT2C over 5-HT2B. AB - Agonism of the 5-HT2C serotonin receptor has been associated with the treatment of a number of diseases including obesity, psychiatric disorders, sexual health, and urology. However, the development of effective 5-HT2C agonists has been hampered by the difficulty in obtaining selectivity over the closely related 5 HT2B receptor, agonism of which is associated with irreversible cardiac valvulopathy. Understanding how to design selective agonists requires exploration of the structural features governing the functional uniqueness of the target receptor relative to related off targets. X-ray crystallography, the major experimental source of structural information, is a slow and challenging process for integral membrane proteins, and so is currently not feasible for every GPCR or GPCR-ligand complex. Therefore, the integration of existing ligand SAR data with GPCR modeling can be a practical alternative to provide this essential structural insight. To demonstrate this, we integrated SAR data from 39 azepine series 5-HT2C agonists, comprising both selective and unselective examples, with our hierarchical GPCR modeling protocol (HGMP). Through this work we have been able to demonstrate how relatively small differences in the amino acid sequences of GPCRs can lead to significant differences in secondary structure and function, as supported by experimental data. In particular, this study suggests that conformational differences in the tilt of TM7 between 5-HT2B and 5-HT2C, which result from differences in interhelical interactions, may be the major source of selectivity in G-protein activation between these two receptors. Our approach also demonstrates how the use of GPCR models in conjunction with SAR data can be used to explain activity cliffs. PMID- 26900769 TI - Pesticide Mixture Toxicity in Surface Water Extracts in Snails (Lymnaea stagnalis) by an in Vitro Acetylcholinesterase Inhibition Assay and Metabolomics. AB - Many chemicals in use end up in the aquatic environment. The toxicity of water samples can be tested with bioassays, but a metabolomic approach has the advantage that multiple end points can be measured simultaneously and the affected metabolic pathways can be revealed. A current challenge in metabolomics is the study of mixture effects. This study aims at investigating the toxicity of an environmental extract and its most abundant chemicals identified by target chemical analysis of >100 organic micropollutants and effect-directed analysis (EDA) using the acetylcholinesterase (AChE) bioassay and metabolomics. Surface water from an agricultural area was sampled with a large volume solid phase extraction (LVSPE) device using three cartridges containing neutral, anionic, and cationic sorbents able to trap several pollutants classes like pharmaceuticals, pesticides, PAHs, PCBs, and perfluorinated surfactants. Targeted chemical analysis and AChE bioassay were performed on the cartridge extracts. The extract of the neutral sorbent cartridge contained most of the targeted chemicals, mainly imidacloprid, thiacloprid, and pirimicarb, and was the most potent AChE inhibitor. Using an EDA approach, other AChE inhibiting candidates were identified in the neutral extract, such as carbendazim and esprocarb. Additionally, a metabolomics experiment on the central nervous system (CNS) of the freshwater snail Lymnaea stagnalis was conducted. The snails were exposed to the extract, the three most abundant chemicals individually, and a mixture of these. The extract disturbed more metabolic pathways than the three most abundant chemicals individually, indicating the contribution of other chemicals. Most pathways perturbed by the extract exposure overlapped with those related to exposure to neonicotinoids, like the polyamine metabolism involved in CNS injuries. Metabolomics for the straightforward comparison between a complex mixture and single compound toxicity is still challenging but, compared to traditional biotesting, is a promising tool due to its increased sensitivity. PMID- 26900770 TI - Use of Phase Transition Curves for Testing Models of the pH-Oscillatory Hydrogen Peroxide-Thiosulfate-Sulfite Reaction. AB - The reaction system hydrogen peroxide-thiosulfate-sulfite in diluted sulfuric acid (HPTS) displays strongly nonlinear dynamics when operated in a continuous flow stirred tank reactor. Due to a crucial role of hydrogen ion during the reaction, this system is a prime example of an inorganic pH-oscillator. Under specific external conditions the system exhibits multiple steady states, periodic oscillations and chaotic behavior. We focus on evaluating alternative kinetic models by exploring phase resetting of the periodic oscillatory regime caused by a single-pulse perturbation with various reacting species. Phase transition curve (PTC), the plot of phase after the resetting against the phase of perturbation, is a convenient characteristic of the oscillatory dynamics adopted as a major tool in this work. Experimental results for hydrogen ions, hydroxide ions, thiosulfate ions, sulfite ions, and hydrogen sulfite ions used as perturbants are systematically compared with calculations under corresponding conditions using two available reaction mechanisms. In addition, we use the stoichiometric network analysis to identify possible core oscillatory subnetworks in the models and choose the one that corresponds best to the measured PTCs. PMID- 26900772 TI - Validation of the Neurological Disorders Depression Inventory for Epilepsy (NDDI E) Serbian version. AB - The Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) was developed and proven efficient for the rapid detection of a major depressive episode in people with epilepsy. This study describes the development, validation, and psychometric properties of the NDDI-E Serbian version. A consecutive sample of 103 patients with epilepsy was assessed using the Beck Depression Inventory (BDI) and the NDDI-E. All patients had no major difficulties in understanding or answering the questions of the Serbian version. Cronbach's alpha coefficient was 0.763. Receiver operating characteristic analysis showed an area under the curve of 0.943 (95% CI; 0.826 to 0.951), a cutoff score of >=14, a sensitivity of 72.2%, a specificity of 95.2%, a positive predictive value of 81.3%, and a negative predictive value of 94.3%. The NDDI-E Serbian version scores were significantly and positively correlated with those of the BDI (p<0.001). The NDDI-E Serbian version constitutes a concise and consistent depression screening instrument for patients with epilepsy. PMID- 26900771 TI - Cell-Penetrating, Guanidinium-Rich Oligophosphoesters: Effective and Versatile Molecular Transporters for Drug and Probe Delivery. AB - The design, synthesis, and biological evaluation of a new family of highly effective cell-penetrating molecular transporters, guanidinium-rich oligophosphoesters, are described. These unique transporters are synthesized in two steps, irrespective of oligomer length, by the organocatalytic ring-opening polymerization (OROP) of 5-membered cyclic phospholane monomers followed by oligomer deprotection. Varying the initiating alcohol results in a wide variety of cargo attachment strategies for releasable or nonreleasable transporter applications. Initiation of oligomerization with a fluorescent probe produces, upon deprotection, a transporter-probe conjugate that is shown to readily enter multiple cell lines in a dose-dependent manner. These new transporters are superior in cell uptake to previously studied guanidinium-rich oligocarbonates and oligoarginines, showing over 2-fold higher uptake than the former and 6-fold higher uptake than the latter. Initiation with a protected thiol gives, upon deprotection, thiol-terminated transporters which can be thiol-click conjugated to a variety of probes, drugs and other cargos as exemplified by the conjugation and delivery of the model probe fluorescein-maleimide and the medicinal agent paclitaxel (PTX) into cells. Of particular significance given that drug resistance is a major cause of chemotherapy failure, the PTX-transporter conjugate, designed to evade Pgp export and release free PTX after cell entry, shows efficacy against PTX-resistant ovarian cancer cells. Collectively this study introduces a new and highly effective class of guanidinium-rich cell penetrating transporters and methodology for their single-step conjugation to drugs and probes, and demonstrates that the resulting drug/probe-conjugates readily enter cells, outperforming previously reported guanidinium-rich oligocarbonates and peptide transporters. PMID- 26900773 TI - The impact of anxiety, seizure severity, executive dysfunction, subjectively perceived psychological deficits, and depression on social function in patients with epilepsy. AB - The impact of anxiety, seizure severity, executive dysfunction, subjectively perceived psychological deficits, and depression on social function in patients with epilepsy (PWE) was analyzed. A brief cognitive screening test (EpiTrack) and an estimation of the last 6 months' cumulative seizure severity (Chalfont seizure severity scale) were performed, and questionnaires on subjectively perceived cognitive deficits (c.I.-Skala), anxiety (State-Trait Anxiety Inventory, STAIX1 and STAIX2), depression (Self Rating Depression Scale, SDS), and social function (Soziale Aktivitat Selbstbeurteilungsskala, SASS) were completed. Forty PWE (aged 41.8 years, SD 16; 24 female, 16 male) were analyzed. Thirty-eight point 5 percent had a score signifying depression in the SDS; 20% had a pathological result in at least one of the anxiety scores. The ANOVA revealed that only anxiety as a trait symptom (STAIX2) had a significant influence on social function apart from the other factors (p<0.004). Additionally there was a trend for a significant influence of depressive symptoms (SDS) on social functioning (p=0.093). Symptoms of anxiety impair the social function of patients with epilepsy apart from depression, cognitive function, and seizure severity. They should be taken into account in the treatment of patients with epilepsy. PMID- 26900774 TI - Talking about epilepsy: Challenges parents face when communicating with their child about epilepsy and epilepsy-related issues. AB - The aim of this qualitative study was to explore the challenges that parents of children with epilepsy experienced when engaging in dialog with their child about epilepsy and epilepsy-related issues. Using a qualitative exploratory approach, interviews were conducted with 34 parents of children with epilepsy (aged 6-16 years), consisting of 27 mothers and 7 fathers. Data were transcribed verbatim and thematically analyzed. Findings revealed five main themes: normalizing epilepsy, the invisibility of epilepsy, information concealment, fear of misinforming the child, and difficulty in discussing particular epilepsy-related issues. Many of the communicative challenges experienced by parents impacted on their ability to engage openly in parent-child dialog about epilepsy in the home. Parents face specific challenges when choosing to communicate with their child about epilepsy, relating to creating a sense of normality, reducing fear of causing their child worry, and having a lack of epilepsy-related knowledge. Healthcare professionals who work closely with families living with epilepsy should remain mindful of the importance of discussing family communication surrounding epilepsy and the challenges parents of children with epilepsy face when talking about epilepsy within the home. PMID- 26900776 TI - Support to mothers of premature babies using NIDCAP method: a non-randomized controlled trial. AB - BACKGROUND: The Newborn Individualized Developmental Care and Assessment Program (NIDCAP) is based on preterm infant's observation during hospitalization and considers infant's behavior as the key to evaluate the level of neurobehavioral maturation. OBJECTIVES: To evaluate the effectiveness of NIDCAP program on mother's support and infant development. STUDY DESIGN: Non-randomized controlled study, including 43 infants of 32 weeks gestation receiving either a Standard Care (SC) or NIDCAP assessment. The Nurse Parent Support Tool (NPST) was given to mothers before discharge to evaluate the support given by NICU staff. Infants' motor, visual and auditory development was investigated by a neurofunctional assessment (NFA) at term and at 3 months. The effect of NIDCAP assessment on length of hospital stay and feeding status at discharge were also evaluated. RESULTS: Mothers in the NIDCAP group awarded higher scores in the majority of the NPST items than mothers in the SC group. NFA at term resulted to be normal in a significant higher percentage of infants that underwent NIDCAP, while no difference could be detected at 3 months. CONCLUSIONS: NIDCAP is an effective program to promote mothers' involvement in infants' care, that, in turn, could endorse infants' neurofunctional development in the short term. PMID- 26900775 TI - Improved survival and neurodevelopmental outcomes among extremely premature infants born near the limit of viability. AB - BACKGROUND: Infants born near the limit of viability are at high risk for death or adverse neurodevelopmental outcomes. It is unclear whether these outcomes have improved over the past 15 years. AIM: To determine if death and neurodevelopmental impairment have declined over the past 15 years in infants born at 22 to 24 weeks' gestation. STUDY DESIGN: Retrospective cohort study. SUBJECTS: We identified infants born at 22 to 24 weeks' gestation in our center in two epochs: 1998-2004 (Epoch 1) and 2005-2011 (Epoch 2). OUTCOME MEASURES: The primary outcome, death or neurodevelopmental impairment, was evaluated at 17-25 months' corrected gestational age with neurologic exams and Bayley Scales of Infant Development. Perinatal characteristics, major morbidities, and outcomes were compared between epochs. RESULTS: Birth weight and gestational age were similar between 170 infants in Epoch 1 and 187 infants in Epoch 2. Mortality was significantly lower in Epoch 2, 55% vs. 42% (p=0.02). Among surviving infants, late-onset sepsis (p<0.01), bronchopulmonary dysplasia (p<0.01), and surgical necrotizing enterocolitis (p=0.04) were less common in Epoch 2. Neurodevelopmental impairment among surviving infants declined from 68% in Epoch 1 to 47% in Epoch 2, p=0.02. Odds of death or NDI were significantly lower in Epoch 2 vs. Epoch 1, OR=0.31 (95% confidence interval; 0.16, 0.58). CONCLUSION: Risk of death or neurodevelopmental impairment decreased over time in infants born at 22 to 24 weeks' gestation. PMID- 26900777 TI - Identification of sources of polycyclic aromatic hydrocarbons based on concentrations in soils from two sides of the Himalayas between China and Nepal. AB - To understand distribution and sources of polycyclic aromatic hydrocarbons (PAHs) in the Himalayas, 77 soil samples were collected from the northern side of the Himalayas, China (NSHC), and the southern side of the Himalayas, Nepal (SSHN), based on altitude, land use and possible trans-boundary transport of PAHs driven by wind from Nepal to the Tibetan Plateau, China. Soils from the SSHN had mean PAH concentration greater than those from the NSHC. Greater concentrations of PAHs in soils were mainly distributed near main roads and agricultural and urban areas. PAHs with 2-3 rings were the most abundant PAHs in the soils from the Himalayas. Concentrations of volatile PAHs were significantly and positively correlated with altitude. Simulations of trajectories of air masses indicated that distributions of soil PAH concentrations were associated with the cyclic patterns of the monsoon. PAH emissions from traffic and combustion of biomass or coal greatly contributed to concentrations of PAHs in soils from the Himalayas. PMID- 26900778 TI - Maternal nationality and developmental delays in young children: Analysis of the data from the national registry in Taiwan. AB - BACKGROUND: With globalization, transnational marriages become more and more common around the world. Children born to immigrant mothers might be more likely to have developmental delays, but studies on this topic are limited and with inconsistent results. AIMS: To determine whether children born to immigrant mothers are more likely to have developmental delays. METHODS AND PROCEDURES: We analyzed the data from the national registry of children with developmental delays from 2009 to 2013 and compared the incidence of developmental delays between children born to immigrant mothers and native mothers. We also performed stratified analyses by age, sex, and geographic area. OUTCOMES AND RESULTS: From 2009 to 2013, 78,946 new cases of developmental delays under 6 years of age were registered, including 5619 (7.1%) born to immigrant mothers. The incidence was higher in children born to native mothers in every year with rate ratios ranging from 1.32 to 1.48, and the differences reached statistical significance even after stratification by age, sex, and geographic area. CONCLUSIONS AND IMPLICATIONS: Children born to immigrant mothers had lower incidence of developmental delays in Taiwan. The result may help reduce the discrimination of foreign spouses and their children. PMID- 26900779 TI - Auditory and visual sustained attention in Down syndrome. AB - BACKGROUND: Sustained attention (SA) is important to task performance and development of higher functions. It emerges as a separable component of attention during preschool and shows incremental improvements during this stage of development. AIMS: The current study investigated if auditory and visual SA match developmental level or are particular challenges for youth with DS. Further, we sought to determine if there were modality effects in SA that could predict those seen in short-term memory (STM). METHODS AND PROCEDURES: We compared youth with DS to typically developing youth matched for nonverbal mental age and receptive vocabulary. Groups completed auditory and visual sustained attention to response tests (SARTs) and STM tasks. OUTCOMES AND RESULTS: Results indicated groups performed similarly on both SARTs, even over varying cognitive ability. Further, within groups participants performed similarly on auditory and visual SARTs, thus SA could not predict modality effects in STM. However, SA did generally predict a significant portion of unique variance in groups' STM. CONCLUSIONS AND IMPLICATIONS: Ultimately, results suggested both auditory and visual SA match developmental level in DS. Further, SA generally predicts STM, though SA does not necessarily predict the pattern of poor auditory relative to visual STM characteristic of DS. PMID- 26900780 TI - Brief report: Growth in polysubstance use among youth in the child welfare system. AB - PURPOSE: This paper establishes foundational knowledge on development of polysubstance use among adolescents in the U.S. child welfare system (CWS). METHOD: Data on U.S. CWS adolescents from the National Study of Child and Adolescent Well-Being were examined for rates of alcohol, marijuana, and hard drug use; and change in use over time. RESULTS: Past 30-day absolute use was highest for alcohol, but daily/near-daily use highest for marijuana. Marijuana use increased at later time points. A correlated growth model suggested covariation in use of the substances. A curve-of-factors model suggested that higher-order factors explain most variation in substance use, except at the last time point. Those with lower use changed the most across time. CONCLUSIONS: Subsequent research among CWS adolescents in the U.S. should consider substances jointly. Prevention should focus on marijuana, and later periods of adolescence and CWS involvement. Youth not thought of as at great risk upon entering the CWS may be most vulnerable. PMID- 26900781 TI - Tobacco and alcohol as risk factors for oesophageal cancer in a high incidence area in South Africa. AB - BACKGROUND: The Eastern Cape Province of South Africa, which includes the former Transkei has high rates of squamous cell oesophageal cancer (OC), thought to be caused mainly by nutritional deficiencies and fungal contamination of staple maize. A hospital-based case-control study was conducted at three of the major referral hospitals in this region to measure, among other suspected risk factors, the relative importance of tobacco smoking and alcohol consumption for the disease in this population. METHODS: Incident cases (n=670) of OC and controls (n=1188) were interviewed using a structured questionnaire which included questions on tobacco and alcohol-related consumption. Odds ratios (ORs) with 95% confidence intervals for each of the risk factors were calculated using unconditional multiple logistic regression models. RESULTS: A monotonic dose response was observed across the categories of each tobacco-related variable in both sexes. Males and females currently smoking a total of >14g of tobacco per day were observed to have over 4-times the odds of developing OC (males OR=4.36, 95% CI 2.24-8.48; females OR=4.56, 95% CI 1.46-14.30), with pipe smoking showing the strongest effect. Similar trends were observed for the alcohol-related variables. The quantity of ethanol consumed was the most important factor in OC development rather than any individual type of alcoholic beverage, especially in smokers. Males and females consuming >53g of ethanol per day had approximately 5 times greater odds in comparison to non-drinkers (males OR=4.72, 95% CI 2.64 8.41; females OR=5.24, 95% CI 3.34-8.23) and 8.5 greater odds in those who smoked >14g tobacco daily. The attributable fractions for smoking and alcohol consumption were 58% and 48% respectively, 64% for both factors combined. CONCLUSION: Tobacco and alcohol use are major risk factors for OC development in this region. IMPACT: This study provides evidence for further reinforcement of cessation of smoking and alcohol consumption to curb OC development. PMID- 26900782 TI - Spacers for Geometrically Well-Defined Water-Soluble Molecular Rulers and Their Application. AB - The synthesis and application of monodisperse oligo(para-phenyleneethynylene)s (oligoPPEs) with side chains that are adjustable to specific needs, such as water solubility, on a very late stage of the multistep synthesis are described. The adjustable side chains allow for circumventing problems associated with the isolation of highly hydrophilic compounds during early stages of a synthesis. Furthermore, these oligoPPEs can be stocked as adaptable advanced building blocks for rapid assembly of tailor-made spacers and rulers. A rapid growth synthesis provides oligoPPEs with alkyne termini protected with the orthogonal groups trimethylsilyl and 1-hydroxy-1-methylethyl (HOP) and with propargyloxy side chains protected with the triisopropylsilyl group. The three protecting groups allow independent modification of the two termini and the side chains. The HOP group not only acts as a protecting group but also as a polar tag for simple product isolation. We demonstrate one application of these oligoPPEs as spacers for the water-soluble Gd rulers of the type Gd-PyMTA-spacer-Gd-PyMTA with Gd-Gd distances of 2.1-10.9 nm. For this purpose, the terminal alkyne units were used for backbone assembly and attachment of the ligand PyMTA, and the porpargyloxy side chains were used to attach water solubilizing poly(ethylene glycol) chains through a click reaction after spacer assembly. PMID- 26900783 TI - Stability and Anharmonic N-H Stretching Frequencies of 1-Methylthymine Dimers: Hydrogen Bonding versus pi-Stacking. AB - Stability of three hydrogen-bonded and six stacked 1-methylthymine (1 mT) dimers was studied with the DFT-D3 method at various temperatures. It was demonstrated that the stacked dimers are slightly less stable than the hydrogen-bonded counterparts. Existence of T-shaped dimers is addressed. Anharmonic couplings that involve N-H stretching modes of the nine species are studied. Surprisingly, we find that N-H stretching modes of the two 1 mT molecules are significantly coupled in four stacked dimers. The presented results shed light on existence of strong mode couplings between the two N-H stretching modes in stacked aromatic species. Our calculations support the proposal ( J. Phys. Chem. A 2011 , 115 , 9429 - 9439 ) that presence of several dimers is responsible for appearance of wide and structured bands in 1 mT homodimers' jet-cooled spectra above 2900 cm( 1). PMID- 26900784 TI - Aza-Conjugate Addition Methodology for the Synthesis of N-Hydroxy-isoindolin-1 ones. AB - Aryl-aldehydes containing ortho-substituted propiolate fragments react with hydroxylamine to afford carbinolamine intermediates that undergo intramolecular aza-conjugate addition reactions to afford N-hydroxy-2.3-dihydro-isoindolin-1 ones that can be reduced to their corresponding isoindolin-1-ones and isoindoles. PMID- 26900785 TI - Lycopene modulates cholinergic dysfunction, Bcl-2/Bax balance, and antioxidant enzymes gene transcripts in monosodium glutamate (E621) induced neurotoxicity in a rat model. AB - The effect of monosodium glutamate (MSG) on brain tissue and the relative ability of lycopene to avert these neurotoxic effects were investigated. Thirty-two male Wistar rats were distributed into 4 groups: group I, untreated (placebo); group II, injected with MSG (5 mg.kg(-1)) s.c.; group III, gastrogavaged with lycopene (10 mg.kg(-1)) p.o.; and group IV received MSG with lycopene with the same mentioned doses for 30 days. The results showed that MSG induced elevation in lipid peroxidation marker and perturbation in the antioxidant homeostasis and increased the levels of brain and serum cholinesterase (ChE), total creatine phosphokinase (CPK), creatine phosphokinase isoenzymes BB (CPK-BB), and lactate dehydrogenase (LDH). Glutathione S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT) activities and gene expression were increased and glutathione content was reduced in the MSG-challenged rats, and these effects were ameliorated by lycopene. Furthermore, MSG induced apoptosis in brain tissues reflected in upregulation of pro-apoptotic Bax while lycopene upregulated the anti-apoptotic Bcl-2. Our results indicate that lycopene appears to be highly effective in relieving the toxic effects of MSG by inhibiting lipid peroxidation and inducing modifications in the activity of cholinesterase and antioxidant pathways. Interestingly, lycopene protects brain tissue by inhibiting apoptosis signaling induced by MSG. PMID- 26900786 TI - Noncoding RNAs of Plant Viruses and Viroids: Sponges of Host Translation and RNA Interference Machinery. AB - Noncoding sequences in plant viral genomes are well-known to control viral replication and gene expression in cis. However, plant viral and viroid noncoding (nc)RNA sequences can also regulate gene expression acting in trans, often acting like 'sponges' that bind and sequester host cellular machinery to favor viral infection. Noncoding sequences of small subgenomic (sg)RNAs of Barley yellow dwarf virus (BYDV) and Red clover necrotic mosaic virus (RCNMV) contain a cap independent translation element that binds translation initiation factor eIF4G. We provide new evidence that a sgRNA of BYDV can globally attenuate host translation, probably by sponging eIF4G. Subgenomic ncRNA of RCNMV is generated via 5' to 3' degradation by a host exonuclease. The similar noncoding subgenomic flavivirus (sf)RNA, inhibits the innate immune response, enhancing viral pathogenesis. Cauliflower mosaic virus transcribes massive amounts of a 600-nt ncRNA, which is processed into small RNAs that overwhelm the host's RNA interference (RNAi) system. Viroids use the host RNAi machinery to generate viroid-derived ncRNAs that inhibit expression of host defense genes by mimicking a microRNA. More examples of plant viral and viroid ncRNAs are likely to be discovered, revealing fascinating new weaponry in the host-virus arms race. PMID- 26900787 TI - Infant birth weight and third trimester maternal plasma markers of vascular integrity: the MIREC study. AB - BACKGROUND: There is paucity of information on mechanisms constituting adverse birth outcomes. We assessed here the relationship between vascular integrity and adverse birth effects. METHODS AND RESULTS: Third trimester maternal plasma (n = 144) from the Maternal-Infant Research on Environmental Chemicals Study (MIREC) was analysed for vascular, inflammatory and oxidative stress markers by HPLC fluorescence, protein array and EIA method. Analysis of the <25th and >75th percentile birth weight subgroups revealed markers associated with birth weight (ETs, MMP-9, VEGF, and 8-isoPGF-2alpha) and gestational age (ET-1, MMP-2, and VEGF). CONCLUSIONS: Mechanistic insights into adverse birth outcome pathways can be achieved by integrating information on multiple biomarkers, physiology using systems biology approach. PMID- 26900791 TI - To drink or not to drink: Harmful drinking is associated with hyperactivation of reward areas rather than hypoactivation of control areas in men. AB - BACKGROUND: The maintenance of harmful alcohol use can be considered a reiterated decision in favour of alcohol in concrete drinking occasions. These decisions are often made despite an intention to quit or reduce alcohol consumption. We tested if a hyperactive reward system and/or an impaired cognitive control system contribute to such unfavourable decision-making. METHODS: In this fMRI study, men with modest to harmful drinking behaviour, which was measured using the Alcohol Use Disorders Identification Test (AUDIT), repeatedly made decisions between alcoholic and nonalcoholic drinks. Based on prior individual ratings, decision pairs were created with an alcoholic decision option considered more desirable but less beneficial by the participant. By correlating AUDIT scores with brain activation during decision-making, we determined areas explicitly related to pro alcohol decisions in men with greater drinking severity. RESULTS: Thirty-eight men participated in our study. Behaviourally, we found a positive correlation between AUDIT scores and the number of decisions for desired alcoholic drinks compared with beneficial nonalcoholic drinks. The fMRI results show that AUDIT scores were positively associated with activation in areas associated with reward and motivation processing (i.e., ventral striatum, amygdala, medial prefrontal cortex) during decisions favouring a desired, nonbeneficial alcoholic drink. Conversely, we did not find hypoactivation in areas associated with self-control (dorsolateral prefrontal cortex). These effects were not present when participants chose a desired, nonbenefical, nonalcoholic drink. LIMITATIONS: The men participating in our study had to be abstinent and would potentially consume an alcoholic drink at the end of the experiment. Hence, we did not define manifest alcohol dependence as an inclusion criterion and instead focused on less severely affected individuals. CONCLUSION: Our results indicate that with growing drinking severity, decisions for alcoholic drinks are associated with increasing activity in reward-associated neural systems, rather than decreasing activity in self-control-associated systems. PMID- 26900792 TI - Cocaine cue-induced dopamine release in the human prefrontal cortex. AB - BACKGROUND: Accumulating evidence indicates that drug-related cues can induce dopamine (DA) release in the striatum of substance abusers. Whether these same cues provoke DA release in the human prefrontal cortex remains unknown. METHODS: We used high-resolution positron emission tomography with [18F]fallypride to measure cortical and striatal DA D2/3 receptor availability in the presence versus absence of drug-related cues in volunteers with current cocaine dependence. RESULTS: Twelve individuals participated in our study. Among participants reporting a craving response (9 of 12), exposure to the cocaine cues significantly decreased [18F]fallypride binding potential (BPND) values in the medial orbitofrontal cortex and striatum. In all 12 participants, individual differences in the magnitude of craving correlated with BPND changes in the medial orbitofrontal cortex, dorsolateral prefrontal cortex, anterior cingulate, and striatum. Consistent with the presence of autoreceptors on mesostriatal but not mesocortical DA cell bodies, midbrain BPND values were significantly correlated with changes in BPND within the striatum but not the cortex. The lower the midbrain D2 receptor levels, the greater the striatal change in BPND and self reported craving. LIMITATIONS: Limitations of this study include its modest sample size, with only 2 female participants. Newer tracers might have greater sensitivity to cortical DA release. CONCLUSION: In people with cocaine use disorders, the presentation of drug-related cues induces DA release within cortical and striatal regions. Both effects are associated with craving, but only the latter is regulated by midbrain autoreceptors. Together, the results suggest that cortical and subcortical DA responses might both influence drug-focused incentive motivational states, but with separate regulatory mechanisms. PMID- 26900793 TI - Elevated prefrontal cortex GABA in patients with major depressive disorder after TMS treatment measured with proton magnetic resonance spectroscopy. AB - BACKGROUND: GABAergic and glutamatergic neurotransmitter systems are central to the pathophysiology of depression and are potential targets of repetitive transcranial magnetic stimulation (rTMS). We assessed the effect of 10-Hz rTMS over the left dorsolateral prefrontal cortex (DLPFC) of patients with major depressive disorder on the levels of medial prefrontal cortex (MPFC) gamma aminobutyric acid (GABA) and the combined resonance of glutamate and glutamine (Glx) as assessed in vivo with proton magnetic resonance spectroscopy ((1)H MRS). METHODS: Currently depressed individuals between the ages of 23 and 68 years participated in a 5-week naturalistic, open-label treatment study of rTMS, with (1)H MRS measurements of MPFC GABA and Glx levels at baseline and following 5 weeks of the rTMS intervention. We applied rTMS pulses over the left DLPFC at 10 Hz and 80%-120% of motor threshold for 25 daily sessions, with each session consisting of 3000 pulses. We assessed therapeutic response using the 24-item Hamilton Rating Scale for Depression (HAMD24). The GABA and Glx levels are expressed as ratios of peak areas relative to the area of the synchronously acquired and similarly fitted unsuppressed voxel water signal (W). RESULTS: Twenty-three currently depressed individuals (7 men) participated in the study. GABA/W in the MPFC increased 13.8% (p = 0.013) in all depressed individuals. There were no significant effects of rTMS on Glx/W. GABA/W and Glx/W were highly correlated in severely depressed patients at baseline but not after TMS. LIMITATIONS: The primary study limitations are the open-label design and the inclusion of participants currently taking stable regimens of antidepressant medications. CONCLUSION: These results implicate GABAergic and glutamatergic systems in the mechanism of action of rTMS for major depression, warranting further investigation in larger samples. PMID- 26900795 TI - Rotational deformities of the long bones can be corrected with rotationally guided growth during the growth phase. AB - Background and purpose - Coronal and sagittal plane long bone deformities can be corrected with guided growth, whereas transverse plane rotational deformities require osteotomy and internal or external fixation. We investigated whether rotational changes can be introduced with the plating technique. Methods - 45 rabbits (6 weeks old) were divided into 3 groups. The unoperated right tibia was used as control. In groups 1 and 3, two plates were placed obliquely to the long axis and in different directions. In group 2, a sham operation was performed with screws. Animals in groups 1 and 2 were followed for 4 weeks. In group 3 the implants were removed 4 weeks after the operation to observe rebound effect, and the animals were followed for another 4 weeks. The tibial torsion was assessed on computed tomography (CT). External rotation was accepted as a negative value. Results - In group 1, mean torsion was -20 degrees (SD 7.9) in the right tibia and -2.9 degrees (SD 7.2) in the left tibia (p < 0.001). In group 2, mean torsion was -23 degrees (SD 4.9) in the right tibia and -26 degrees (SD 6.5) in the left tibia (p = 0.2). In group 3, mean torsion was -21 degrees (SD 6.3) in the right tibia and -9.5 degrees (SD 5.3) in the left tibia (p < 0.001). Intergroup evaluation for left torsion showed a significant difference between group 2 and the other groups (p < 0.001). When the rebound effect was evaluated, there was no statistically significant difference between groups 1 and 3 (p = 0.08). Interpretation - A rotational change was attained with this technique. Although a rebound effect was seen after implant removal, it did not reach statistical significance. The final rotational change remained constant. PMID- 26900796 TI - The efficacy and safety of hyperbaric oxygen therapy in traumatic brain injury. PMID- 26900794 TI - Autophagy and Obesity-Related Lung Disease. AB - Obesity-related disease is a significant source of premature death and economic burden globally. It is also a common comorbidity in patients suffering from lung disease, affecting both severity and treatment success. However, this complex association between obesity and the lung is poorly understood. Autophagy is a self-recycling homeostatic process that has been linked to beneficial or deleterious effects, depending on the specific lung disease. Obesity affects autophagy in a tissue-specific manner, activating autophagy in adipocytes and impairing autophagy in hepatocytes, immune cells, and pancreatic beta-cells, among others. Obesity is also characterized by chronic low-grade inflammation that can be modulated by the pro- and antiinflammatory effects of the autophagic machinery. Scant evidence exists regarding the impact of autophagy in obesity related lung diseases, but there are communal pathways that could be related to disease pathogenesis. Important signaling molecules in obesity, including IL-17, leptin, adiponectin, NLRP3 inflammasome, and TLR-4, have been implicated in the pathogenesis of lung disease. These mediators are known to be modulated by autophagy activity. In this perspective, we highlight the recent advances in the understanding of autophagy in obesity-related conditions, as well as the potential mechanisms that can link autophagy and obesity in the pathogenesis of lung disease. PMID- 26900797 TI - Prelamin A processing, accumulation and distribution in normal cells and laminopathy disorders. AB - Lamin A is part of a complex structural meshwork located beneath the nuclear envelope and is involved in both structural support and the regulation of gene expression. Lamin A is initially expressed as prelamin A, which contains an extended carboxyl terminus that undergoes a series of post-translational modifications and subsequent cleavage by the endopeptidase ZMPSTE24 to generate lamin A. To facilitate investigations of the role of this cleavage in normal and disease states, we developed a monoclonal antibody (PL-1C7) that specifically recognizes prelamin A at the intact ZMPSTE24 cleavage site, ensuring prelamin A detection exclusively. Importantly, PL-1C7 can be used to determine prelamin A localization and accumulation in cells where lamin A is highly expressed without the use of exogenous fusion proteins. Our results show that unlike mature lamin A, prelamin A accumulates as discrete and localized foci at the nuclear periphery. Furthermore, whereas treatment with farnesylation inhibitors of cells overexpressing a GFP-prelamin A fusion protein results in the formation of large nucleoplasmic clumps, these aggregates are not observed upon similar treatment of cells expressing endogenous prelamin A or in cells lacking ZMPSTE24 expression and/or activity. Finally, we show that specific laminopathy-associated mutations exhibit both positive and negative effects on prelamin A accumulation, indicating that these mutations affect prelamin A processing efficiency in different manners. PMID- 26900798 TI - Technologies for assessment of bone reflecting bone strength and bone mineral density in elderly women: an update. AB - Reduced bone mineral density is a strong risk factor for fracture. The WHO's definition of osteoporosis is based on bone mineral density measurements assessed by dual x-ray absorptiometry. Several on other techniques than dual x-ray absorptiometry have been developed for quantitative assessment of bone, for example, quantitative ultrasound and digital x-ray radiogrammetry. Some of these techniques may also capture other bone properties than bone mass that contribute to bone strength, for example, bone porosity and microarchitecture. In this article we give an update on technologies which are available for evaluation primarily of bone mass and bone density, but also describe methods which currently are validated or are under development for quantitative assessment of other bone properties. PMID- 26900799 TI - A preliminary cost-effectiveness analysis of hepatitis E vaccination among pregnant women in epidemic regions. AB - Objective To estimate the cost-effectiveness of hepatitis E vaccination among pregnant women in epidemic regions. Methods A decision tree model was constructed to evaluate the cost-effectiveness of 3 hepatitis E virus vaccination strategies from societal perspectives. The model parameters were estimated on the basis of published studies and experts' experience. Sensitivity analysis was used to evaluate the uncertainties of the model. Results Vaccination was more economically effective on the basis of the incremental cost-effectiveness ratio (ICER< 3 times China's per capital gross domestic product/quality-adjusted life years); moreover, screening and vaccination had higher QALYs and lower costs compared with universal vaccination. No parameters significantly impacted ICER in one-way sensitivity analysis, and probabilistic sensitivity analysis also showed screening and vaccination to be the dominant strategy. Conclusion Screening and vaccination is the most economical strategy for pregnant women in epidemic regions; however, further studies are necessary to confirm the efficacy and safety of the hepatitis E vaccines. PMID- 26900801 TI - Red blood cell distribution width in iron-deficient young children. PMID- 26900800 TI - Combining p53 stabilizers with metformin induces synergistic apoptosis through regulation of energy metabolism in castration-resistant prostate cancer. AB - Since altered energy metabolism is a hallmark of cancer, many drugs targeting metabolic pathways are in active clinical trials. The tumor suppressor p53 is often inactivated in cancer, either through downregulation of protein or loss-of function mutations. As such, stabilization of p53 is considered as one promising approach to treat those cancers carrying wild type (WT) p53. Herein, SIRT1 inhibitor Tenovin-1 and polo-like kinase 1 (Plk1) inhibitor BI2536 were used to stabilize p53. We found that both Tennovin-1 and BI2536 increased the anti neoplastic activity of metformin, an inhibitor of oxidative phosphorylation, in a p53 dependent manner. Since p53 has also been shown to regulate metabolic pathways, we further analyzed glycolysis and oxidative phosphorylation upon drug treatments. We showed that both Tennovin-1 and BI2536 rescued metformin-induced glycolysis and that both Tennovin-1 and BI2536 potentiated metformin-associated inhibition of oxidative phosphorylation. Of significance, castration-resistant prostate cancer (CRPC) C4-2 cells show a much more robust response to the combination treatment than the parental androgen-dependent prostate cancer LNCaP cells, indicating that targeting energy metabolism with metformin plus p53 stabilizers might be a valid approach to treat CRPC carrying WT p53. PMID- 26900802 TI - Lopinavir/ritonavir enhanced the antimalarial activity of amodiaquine and artesunate in a mouse model of Plasmodium berghei. AB - Treatment of malaria and HIV in co-infected patients remains a challenge due to the limited information on interaction between drugs used for the treatment of the two infections. Thus, this study evaluated the interaction between lopinavir/ritonavir (LR) and artesunate (AS), amodiaquine (AQ) or a fixed dose of AS/AQ in a mouse model of chloroquine-resistant Plasmodium berghei. Combination of LR with graded doses of AS or AQ resulted in a significant reduced ED50. In addition, parasites cleared completely from day 3 till day 21 post-infection in animals infected, treated with AS/AQ alone or AS/AQ with LR and all the animals survived till day 21 post-infection. In contrast, survival on day 21 in animals treated with AQ alone or AQ with LR was 20 and 60%, respectively. It appears that the protease inhibitor LR enhanced the antimalarial drugs AS and AQ. PMID- 26900803 TI - Present Your Paper (#PresentYourPaper): A New Social Media Initiative. PMID- 26900804 TI - Transdisciplinary tour-de-force: The Canadian National Transplant Research Program. AB - The Canadian National Transplant Research Program, launched in 2013 with funding from the Canadian Institutes for Health Research and partners, bridges research in the fields of solid organ transplant, hematopoietic cell transplant, and organ donation. We describe the philosophy, structure, accomplishments, and challenges faced by the Canadian National Transplant Research Program to expand on facilitators and overcome roadblocks to successfully developing a transdisciplinary national research structure. PMID- 26900806 TI - Angiotensin-Converting Enzyme Inhibitors-Beneficial Effects Seen in Many Patient Groups May Not Extend to Kidney Transplant Recipients. PMID- 26900807 TI - Care of Transplant Recipients in Primary Practice. PMID- 26900808 TI - Jon van Rood, FRCP: Senior Consultant Europdonor Foundation. PMID- 26900809 TI - A Primer on Bayesian Decision Analysis With an Application to a Kidney Transplant Decision. AB - A clinical decision support system (CDSS) is a computer program, which is designed to assist health care professionals with decision making tasks. A well developed CDSS weighs the benefits of therapy versus the cost in terms of loss of quality of life and financial loss and recommends the decision that can be expected to provide maximum overall benefit. This article provides an introduction to developing CDSSs using Bayesian networks, such CDSS can help with the often complex decisions involving transplants. First, we review Bayes theorem in the context of medical decision making. Then, we introduce Bayesian networks, which can model probabilistic relationships among many related variables and are based on Bayes theorem. Next, we discuss influence diagrams, which are Bayesian networks augmented with decision and value nodes and which can be used to develop CDSSs that are able to recommend decisions that maximize the expected utility of the predicted outcomes to the patient. By way of comparison, we examine the benefit and challenges of using the Kidney Donor Risk Index as the sole decision tool. Finally, we develop a schema for an influence diagram that models generalized kidney transplant decisions and show how the influence diagram approach can provide the clinician and the potential transplant recipient with a valuable decision support tool. PMID- 26900810 TI - Acute Fibrinoid Organizing Pneumonia in Lung Transplant: The Most Feared Allograft Dysfunction. PMID- 26900811 TI - Prevalence of IgA Antibodies to beta2-Glycoprotein I: A Population-Dependent Feature? PMID- 26900812 TI - Activation of Complement C3 Does Not Hamper the Outcome of Experimental Intramuscular Islet Transplantation. PMID- 26900813 TI - T Cell PTLD Successfully Treated With Single-Agent Brentuximab Vedotin First-Line Therapy. PMID- 26900814 TI - Ovarian Low-grade Serous Carcinoma: A Clinicopathologic Study of 33 Cases With Primary Surgery Performed at a Single Institution. AB - Ovarian low-grade serous carcinoma (LGSC) is an entity with distinct pathologic and clinical features. The number of studies on this type of tumor is limited. In this article, we present our experience with 33 cases of ovarian LGSC with primary surgical treatment at our institution. For comparison, a cohort of ovarian high-grade serous carcinoma (HGSC) was also studied. Clinical information was obtained from the patients' charts or from the treating physicians. Hematoxylin and eosin slides were reviewed of 28 available LGSCs, and the following parameters were recorded: presence/absence of a serous borderline tumor (SBT), presence/absence of micropapillary/cribriform pattern (MP/CP), architectural pattern in the invasive component, and presence/absence of desmoplasia or fibrosis. The incidence of ovarian LGSC was 4.7%. LGSC patients ranged in age from 19 to 79 years (mean, 52 y), with 21.2% younger than 40 years. HGSC patients ranged in age from 38 to 90 years (mean, 62 y), with 1.6% younger than 40 years. LGSCs were staged as follows: stage I (2), stage III (23), and stage IV (8). Twenty-eight of 33 LGSC cases had concurrent SBT, with this component accounting for >50% of the neoplasm in 15 cases. In addition, MP/CP was noted in 19 cases. Invasion patterns included micropapillae (93%), cribriform nests (74%), elongated papillae (26%), glandular (44.4%), medium-sized papillae (33.3%), solid nests (22.2%), macropapillae (19%), and single cells (19%). In addition, desmoplasia (44.4%) and fibrosis (37%) were noted. Follow-up data ranging from 13 to 195 months (median 61.2 mo) were available on 30/33 LGSC patients: 18 (60%) were dead of disease; 1 (3.3%) was dead of other cause; 5 (16.7%) were alive with disease; and 6 (20%) had no evidence of disease. Follow up data from 1 to 169 months (median 48 mo) were available on 185 HGSC patients: 132 (71.4%) were dead of disease; 3 (1.6%) were dead of other cause; 21 (11.4%) were alive with disease; and 29 (15.7%) had no evidence of disease. Ovarian LGSC is rare with a predilection for younger patients relative to HGSC. Most LGSC cases are associated with SBT with an MP/CP, and their invasive component usually contains a micropapillary pattern. Most patients with ovarian LGSC present with advanced-stage disease and have a short-term survival advantage over patients with HGSC (estimated 5 y survival: 62.3% vs. 43.9%). However, over a prolonged period of time, this survival advantage decreases (estimated 10 y survival: 21.2% vs. 22.7%). PMID- 26900815 TI - BAP1 Immunohistochemistry and p16 FISH in the Diagnosis of Sarcomatous and Desmoplastic Mesotheliomas. AB - The separation of sarcomatous and desmoplastic mesotheliomas from benign organizing pleuritis can be morphologically very difficult. Deletion of p16 (CDKN2A) by fluorescence in situ hybridization (FISH) testing appears to be a reliable marker of malignancy in mesothelial proliferations, and more recently it has been reported that, in this setting, loss of BAP1 by immunohistochemistry is only seen in malignant mesotheliomas. To determine how useful these tests are with sarcomatous and desmoplastic mesotheliomas, we examined 20 such tumors. Loss of BAP1 was seen in 3/20 (15%) and deletion of p16 by FISH was seen in 16/20 (80%) cases. Loss of one or the other marker was observed in 17/20 (85%). We also examined 13 sarcomatoid carcinomas, an important differential diagnosis of sarcomatoid mesotheliomas, and found that BAP1 was never lost, but p16 was deleted in 3/11 (27%). We conclude that: (1) BAP1 immunohistochemistry is relatively insensitive in the context of sarcomatous and desmoplastic mesotheliomas, but as a matter of time and cost efficiency may nonetheless be a useful first approach to the problem; (2) deletion of p16 by FISH is considerably more sensitive, but there remain a proportion of cases in which p16 is not deleted; (3) a small improvement in sensitivity can be achieved by using both markers; (4) in the context of a spindle cell malignant tumor in the pleura or peritoneum, which morphologically might be a metastatic sarcomatoid carcinoma or a mesothelioma, the finding of BAP1 loss favors mesothelioma, but p16 FISH cannot be used to separate sarcomatous mesotheliomas from sarcomatoid carcinomas. PMID- 26900817 TI - Significance of Paneth Cells in Histologically Unremarkable Rectal Mucosa. AB - Paneth cell metaplasia of the rectal epithelium is a common histologic finding in patients with chronic inflammatory bowel disease. However, the clinical significance of isolated Paneth cells in otherwise unremarkable rectal mucosa has not been extensively examined. This study examined the frequency and clinical correlates of rectal Paneth cells in 245 biopsies obtained from patients between the ages of 2 weeks to 20 years in a pediatric tertiary care facility from 2010 to 2011. The specimens comprised 193 endoscopic pinch biopsies and 52 rectal suction biopsies. All 245 cases were endoscopically and histologically unremarkable with no prominence of eosinophils, no altered mucosal architecture, and no inflammation. Paneth cells were present in 42 cases (17.1%), which is higher than previous reports. Only 1 of 42 patients with rectal Paneth cells was subsequently diagnosed with Crohn disease. In our study population, the finding of Paneth cells was associated with young age, and the incidence of Paneth cell cases decreased with increasing age (chi=13.69, P=0.0002). Constipation was the most common presenting symptom in patients with rectal Paneth cells and was highly associated with the presence of Paneth cells (odds ratio 4.5, 95% confidence interval: 2.2-9.0). Paneth cells in otherwise unremarkable pediatric rectal biopsies are not rare and frequently occur in common conditions such as idiopathic constipation. PMID- 26900816 TI - Fumarate Hydratase-deficient Renal Cell Carcinoma Is Strongly Correlated With Fumarate Hydratase Mutation and Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome. AB - Hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cell carcinomas (RCC) are difficult to diagnose prospectively. We used immunohistochemistry (IHC) to identify fumarate hydratase (FH)-deficient tumors (defined as FH negative, 2-succinocysteine [2SC] positive) in cases diagnosed as "unclassified RCC, high grade or with papillary pattern," or "papillary RCC type 2," from multiple institutions. A total of 124 tumors (from 118 patients) were evaluated by IHC for FH and 2SC. An FH deficiency was found in 24/124 (19%) cases. An indeterminate result (only 1 marker abnormal) was found in 27/124 (22%) cases. In a tissue microarray of 776 RCCs of different types, only 2 (0.5%) tumors, initially considered papillary type 2, were FH deficient. FH mutations were found in 19/21 FH-deficient tumors (with confirmed germline mutations in 9 of 9 tumors in which germline status could be assessed) and in 1/26 FH indeterminate tumors identified by IHC. No FH mutations were found in 2/21 FH deficient RCCs, 25/26 FH-indeterminate RCCs, and 10/10 RCCs demonstrating FH expression by IHC. Patients with FH-deficient RCC had a median age of 44 years (range, 21 to 65 y). Average tumor size was 8.2 cm (range, 0.9 to 18 cm). FH deficient RCCs were characterized by at least focal macronucleoli and demonstrated 2 or more growth patterns in 93% cases. Papillary was the most common (74%) and dominant (59%) pattern, whereas other common patterns included: solid (44%), tubulocystic (41%), cribriform (41%), and cystic (33%). At presentation, 57% were stage >=pT3, 52% had positive nodes, and 19% had distant metastases. After a mean follow-up of 27 months (range, 1 to 114 mo), 39% of patients were dead of disease, and 26% had disease progression. We conclude that FH and 2SC are useful IHC ancillary tools, which allow recognition of FH deficient RCC. PMID- 26900818 TI - Spectrum of Cystic Epithelial Tumors of the Prostate: Most Cystadenocarcinomas Are Ductal Type With Intracystic Papillary Pattern. AB - Cystic epithelial tumors arising from the prostate are rare, and their full histologic spectrum has yet to be defined. Herein, we present 8 examples of prostatic cystic tumors including 1 giant multilocular cystadenoma and 7 cystadenocarcinomas. We divided the cystadenocarcinomas into "giant multilocular" cystadenocarcinoma (3) and "microscopic" cystadenocarcinoma (4) because of their differing clinical presentations with clinically apparent cystic masses in the former. The cystadenoma was an 11 cm multilocular cystic pelvic tumor in a 55 year-old man who presented with lower urinary tract symptoms. The cystadenoma was lined predominantly by benign acinar cells and had a distinct basal cell layer. No recurrence occurred 3 months after resection. The 3 patients with giant multilocular cystadenocarcinomas were 62 to 82 years old, had large pelvic cystic masses (up to 16 cm), and 2 presented with obstructive urinary and lower intestinal tract symptoms. One giant multilocular cystadenocarcinoma had a markedly high cystic fluid prostate-specific antigen at >80,000 ng/mL. All 3 giant multilocular cystadenocarcinomas were ductal adenocarcinoma with exuberant intracystic papillary formations. One tumor was associated with a high-grade noncystic conventional (acinar) adenocarcinoma (Gleason score 9 [ISUP grade group 5]). Follow-up on the 3 giant multilocular cystadenocarcinoma cases (7 to 21 mo) showed multiple metastases in 1 patient but was attributed to the high-grade conventional adenocarcinoma component. In addition, we described 4 examples of microscopic cystadenocarcinomas that were small (<=1 cm) solitary or multiple cystic tumors identified on pathologic examination of the prostate. In 3 of 4 microscopic cystadenocarcinomas the lining was ductal adenocarcinoma with occasional to exuberant papillae and appeared similar to the smaller cysts in the giant multilocular cystadenocarcinomas. One of the 4 microscopic cystadenocarcinomas had an acinar adenocarcinoma lining with occasional papillae and was associated with a conventional adenocarcinoma. Follow-up of the 4 patients with microscopic cystadenocarcinoma (1 to 14 mo) showed no evidence of disease. Review of literature highlighted similarities between the findings in our cases and previously published prostatic cystadenocarcinomas, including the markedly high cystic fluid prostate-specific antigen level in giant multilocular cystadenocarcinomas and the typical ductal adenocarcinoma morphology with intracystic papillary pattern. In conclusion, cystic epithelial tumors of the prostate exhibit unique clinicopathologic features. Cystadenocarcinomas, whether the clinically apparent giant multilocular form or the incidentally identified microscopic type, represent a rare underrecognized pattern of prostatic adenocarcinoma mostly within the histologic spectrum of the ductal variant. PMID- 26900819 TI - Vocal tract characteristics in Parkinson's disease. AB - PURPOSE OF REVIEW: Voice tremor is strongly linked to the Parkinson's disease speech-voice symptom complex. Little is known about the underlying anatomic source(s) of voice tremor when it occurs. We review recent literature addressing this issue. Additionally we report findings from a study we conducted employing rating of vocal tract structures viewed using nasolaryngoscopy during vocal and nonspeech tasks. RECENT FINDINGS: In Parkinson's disease, using laryngeal electromyography, tremor has not been identified in muscles in the vocal folds even when perceived auditorily. Preliminary findings using nasolaryngoscopy suggest that Parkinson's disease voice tremor is not associated with the vocal folds and may involve the palate, the global larynx, and the arytenoids. Tremor in the vertical larynx on /a/, and tremor in the arytenoid cartilages on /s/ differentiated patients with Parkinson's disease from neurologically healthy controls. Visual reliable detection of tremor when it is absent or borderline present, is challenging. SUMMARY: Parkinson's disease voice tremor is likely to be related to oscillatory movement in structures across the vocal tract rather than just the vocal folds. To progress clinical practice, more refined tools for the visual rating of tremor would be beneficial. How far voice tremor represents a functionally significant factor for speakers would also add to the literature. PMID- 26900820 TI - Reconstructive techniques in skull base surgery after resection of malignant lesions: a wide array of choices. AB - PURPOSE OF REVIEW: In this manuscript, we will provide a panorama of the current status of skull base reconstruction following endoscopic endonasal or open resection of malignant lesions, focusing on novel options and recent modifications of previously described techniques. RECENT FINDINGS: New developments in skull base reconstruction continue to arise, mostly as in the form of vascularized pedicled flaps that can be used following endoscopic and open resections of the skull base. SUMMARY: Resection of skull base tumors, often creating large dural defects that couple with extensive intradural dissection, involving multiple cisterns or the third ventricle, may lead to high-flow cerebrospinal fluid leaks. Reconstruction of the skull base is paramount to achieve an uncomplicated postoperative course. Repair of small dural defects can be reliably achieved using a multilayer grafting technique, which yields a high success rate (>90%). Repair of larger defects associated with a high-flow cerebrospinal fluid leak, or defects in previously irradiated fields, often requires a local or regional pedicled vascularized graft as the first reconstructive choice. When these are unavailable, free microvascular tissue transfer remains an option. PMID- 26900821 TI - Review of differential diagnosis and management of spasmodic dysphonia. AB - PURPOSE OF REVIEW: The recent literature on spasmodic dysphonia is reviewed with regard to pathogenesis, differential diagnosis, treatment options, audits, and current methods of management. RECENT FINDINGS: Advances in technology have enabled clinicians to better understand the connection between brain and laryngeal function and dysfunction. Refinements in imaging and genetic investigation techniques have led to advances in the understanding of the underlying mechanism of this neurolaryngeal disorder. Development of diagnostic assessment tools and measures of quality of life hold the potential to improve treatment and care. SUMMARY: Fifty articles published between 2014 and 2015 were selected for this review. The sources were drawn from several clinical specialties: 54% come under the scope of laryngology, 32% from neurology, and 14% from other areas. It remains poorly understood, misdiagnosed, and underdiagnosed. Its identification, diagnosis, treatment selection, and coordination of care require an expert specialist multidisciplinary team. More training is required to help people who have this chronic and psychosocially disabling voice disorder, which impinges on all aspects of their lives. Spasmodic dysphonia is now classified as a 'rare' disease in the United States. This designation will assist in international standards of diagnosis, assessment, treatment, and management. PMID- 26900822 TI - A review of diet standardization and bolus rheology in the management of dysphagia. AB - PURPOSE OF REVIEW: Texture modification is a widespread practice as a strategy for the management of dysphagia and can be very effective in individual cases. However, it is often performed in a qualitative, subjective manner and practices vary internationally according to multiple sets of national guidelines. This article aims to identify best practice by reviewing the theory and practice of texture modification, focussing on recent advances. RECENT FINDINGS: Instrumental assessment of texture modification in vivo is challenging, and studies including rheology and perception have indicated that fluid viscosity is only one of many factors affecting texture modification in practice. Systematic reviews have identified a historical lack of high-quality clinical evidence, but recent controlled studies are beginning to identify positive and negative aspects of thickened fluids. Research and practice to date have been limited by the lack of control and standardization of foods and drinks. However in 2015 a not-for-profit organization, the International Dysphagia Diet Standardisation Initiative, has published a framework for texture modification from thin liquids to solid foods based on all the existing documentation and guidance, and the - limited - available clinical evidence. SUMMARY: Rheology exists in the lab; however, normal practice is often subjective or lacking control and standardization. In the near future, cohesion of practice and the availability of practical standardization tools may increase awareness and use of rheology. PMID- 26900823 TI - Evaluation of Nonmydriatic Hand-held Optic Disc Photography Grading in the Philadelphia Glaucoma Detection and Treatment Project. AB - PURPOSE: To determine the reproducibility of optic disc photograph grading obtained by a hand-held fundus camera and to determine the diagnostic value of these photographs in detecting patients with glaucoma in a community-based glaucoma-detection program. MATERIALS AND METHODS: Patients underwent slit-lamp examination by an ophthalmologist who graded each patient's optic discs using 2 methods: cup-to-disc ratio (CDR) and disc damage likelihood scale (DDLS). After a comprehensive glaucoma evaluation, patients were diagnosed as having "glaucoma," "glaucoma suspect," or "no glaucoma." Nonmydriatic, monoscopic optic disc photographs were then taken with a portable digital imaging device. On a different day, the same examiner and a second observer graded the disc photographs in a masked manner and determined a diagnostic impression based only on the disc photographs. RESULTS: Of the 1649 patients examined, 119 subjects were randomly selected according to 3 groups of diagnoses: "glaucoma" (n=36), "glaucoma suspect" (n=50), and "no glaucoma" (n=33). For CDR, the intraobserver agreement was 0.71 and the interobserver agreement was 0.69. For disc DDLS, the intraobserver agreement was 0.65 and the interobserver agreement was 0.67. The area under the receiver-operating characteristic distinguishing between normal and glaucoma was 0.88 and 0.86 for CDR and disc DDLS, respectively. CONCLUSIONS: Nonmydriatic, monoscopic disc photographs obtained by a hand-held camera had only moderate disc grading reproducibility. This could be due to a reduced quality of images, making interpretation more challenging, due to taking photographs through small pupils by a hand-held camera and the high percentage of patients with significant cataracts. PMID- 26900824 TI - Raised Intraocular Pressure in Nonjuvenile Idiopathic Arthritis-Uveitis Children: Risk Factors and Effect on Retinal Nerve Fiber Layer. AB - PURPOSE: To determine risk factors for intraocular pressure (IOP) elevation and glaucoma in children with nonjuvenile idiopathic arthritis-related uveitis and any IOP-related changes in the retinal nerve fiber layer (RNFL) thickness. PATIENTS AND METHODS: Clinical data were collected from children attending a tertiary referral uveitis clinic between May 2010 and October 2012. We assigned 206 eyes of 103 children into 32 normal eyes, 108 normotensive uveitics (NU), 41 hypertensive uveitics (HU: raised IOP without glaucomatous disc), and 25 glaucomatous uveitics (GU: raised IOP with glaucomatous disc). Risk factors for raised IOP, glaucoma and steroid response (SR) were evaluated and RNFL thickness across groups was compared with determine changes related to raised IOP. RESULTS: IOP elevation occurred in 40 patients (38.8%) or 66/174 eyes with uveitis (37.9%); and SR occurred in 35.1% of all corticosteroid-treated eyes. Chronic uveitis was a significant risk factor for raised IOP [odds ratio (OR)=9.28, P=0.001], glaucoma, and SR (OR=8.4, P<0.001). Higher peak IOP was also a risk factor for glaucoma (OR=1.4, P=0.003). About 70% of SR eyes were high responders (IOP increase >15 mm Hg from baseline), associated with younger age and corticosteroid injections. Although no significant RNFL thinning was detected between HU and NU eyes, significant thinning was detected in the inferior quadrant of GU (121.3+/-28.9 MUm) compared with NU eyes (142.1+/-32.0 MUm, P=0.043). CONCLUSIONS: Children with chronic uveitis are at higher risk of raised IOP and glaucoma. Thinning of the inferior RNFL quadrant may suggest glaucomatous changes in uveitic children with raised IOP. PMID- 26900825 TI - Effect of Switching From Latanoprost to Bimatoprost in Primary Open-Angle Glaucoma Patients Who Experienced Intraocular Pressure Elevation During Treatment. AB - PURPOSE: We investigated the intraocular pressure (IOP) variations after switching from 0.005% latanoprost to 0.01% bimatoprost in open-angle glaucoma patients who experienced IOP elevation during treatment. PATIENTS AND METHODS: Retrospective, interventional cohort study. Of the 625 patients with open-angle glaucoma, we included 41 patients on latanoprost who showed a peak IOP increase of at least 15% [assessed during the water drinking test (WDT)2] relative to the peak IOP measured during the previous WDT (WDT1). MAIN OUTCOME MEASURE: Baseline, peak, and IOP measurements at each timepoint (15, 30, and 45 min) during all 3 WDT sessions (WDT1, WDT2, and WDT3) were measured. RESULTS: The mean peak IOP was 15.6 mm Hg (SE, 0.73) during WDT1; 21.1 mm Hg (SE, 0.73) during WDT2; and 16.1 mm Hg (SE, 0.73) during WDT3 (P<0.001, repeated-measures analysis of variance). Comparing WDT1 versus WDT2, the mean peak IOP difference was 5.5 mm Hg (P<0.001); for WDT1 versus WDT3, the difference was 0.5 mm Hg (P=0.312); for WDT2 versus WDT3, the mean difference was -5.0 mm Hg (P<0.001). The mean IOP at each timepoint during the WDT sessions was significantly different between WDT1 and WDT2 and between WDT2 and WDT3. CONCLUSIONS: Our study suggests that glaucoma patients on latanoprost who experienced IOP elevation during the course of therapy may benefit from switching to bimatoprost. This alternative can potentially postpone more costly or invasive treatment options. PMID- 26900826 TI - The Maccabi Glaucoma Study: Treatment Patterns and Persistence With Glaucoma Therapy in a Large Israeli Health Maintenance Organization. AB - PURPOSE: To describe treatment patterns, adherence, and persistence with initial therapy among glaucoma patients in the community. MATERIALS AND METHODS: A population-based historical prospective cohort study, using the electronic medical databases of Maccabi Healthcare Services, a 2 million member health maintenance organization in Israel. Newly diagnosed glaucoma patients between 2003 and 2010, who purchased at least 1 antiglaucoma medication, were followed up to December 31, 2012. Outcome measures included medication adherence analyzed by proportion of days covered by drugs during follow-up time, and persistence with initial therapy measured by time until switch or discontinuation of first-line therapy. RESULTS: A total of 5934 incident definite glaucoma patients were identified, 13% of whom were nonadherent with therapy (covered <20% of the follow up time), and only 25% exhibited high adherence (covered at least 80% of the follow-up period). Adherence was positively associated with female sex, age, socioeconomic status, frequent follow-up visits, and higher baseline intraocular pressure. Lower median adherence (P<0.01) was observed among patients of normal tension glaucoma (52%) and angle closure (59%) as compared with open angle (65%) and exfoliation glaucoma (68%). Patients treated by glaucoma specialists had similar adherence to those treated by general ophthalmologists (proportion of days covered=65% vs. 63%, P=0.42). Persistence with initial line of therapy varied by type of medication, with prostaglandin initiators exhibiting the highest persistence (13% reduced likelihood of switch or discontinuation as compared with beta-blockers, P<0.01) and alpha-agonists the lowest persistence (39% increased likelihood of switch or discontinuation as compared with beta blockers, P<0.01). CONCLUSIONS: This large-scale analysis of real-world use of glaucoma medications reveals that adherence to glaucoma therapy is associated with medication type, patient's sex, age, socioeconomic status, type of glaucoma, follow-up visits, and baseline intraocular pressure. PMID- 26900827 TI - Evaluation of Retinal Nerve Fiber Layer and Ganglion Cell Complex Thickness in Unilateral Exfoliation Syndrome Using Optical Coherence Tomography. AB - PURPOSE: To evaluate retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thickness by using optical coherence tomography in unilateral exfoliation syndrome (XFS) and to assess whether exfoliation itself is an independent risk factor for glaucomatous optic nerve damage. MATERIALS AND METHODS: Thirty exfoliative eyes of unilateral XFS cases, 30 fellow eyes of unilateral exfoliation, and 30 eyes of healthy subjects were enrolled the study. Peripapillary RNFL and macular GCC thickness measurements by Cirrus HD OCT (Carl Zeiss Meditec, Dublin, CA) were performed on all subjects. RESULTS: RNFL thickness in superior quadrant was significantly different between groups (P=0.025) and it was thinner in XFS than healthy subjects (P=0.020). All GCC parameters except GCC thickness in inferior quadrant were significantly different between groups (P=0.110 for inferior quadrant, P<0.046 for other GCC parameters). GCC were thinner in XFS than healthy subjects except inferior and inferonasal quadrants (P=0.091, 0.051 for inferior and inferonasal quadrants, respectively, P<0.039 for other GCC parameters). Minimum GCC thickness, GCC thicknesses in superior, and inferonasal quadrants were significantly thinner in fellow eyes than healthy subjects (P=0.011, 0.013, 0.047, respectively). CONCLUSIONS: XFS is related with thinner RNFL and GCC even in normal intraocular pressure values, similar optic disc parameters and visual field results. XFS may be an independent risk factor for glaucomatous optic nerve damage. So, further studies are needed to evaluate whether exfoliation itself is an independent risk factor for optic nerve damage. PMID- 26900828 TI - The Prevalence and the Incidence of Diagnosed Open-Angle Glaucoma and Diagnosed Angle-Closure Glaucoma: Changes From 2001 to 2010. AB - PURPOSE: To explore the trends in diagnosed open-angle glaucoma (OAG) and diagnosed angle-closure glaucoma (ACG) in Taiwan during the period of 2001 to 2010. MATERIALS AND METHODS: Data were sourced from the National Longitudinal Health Insurance Database 2000 (LHID2000). The study population comprised all patients with a diagnosis of OAG or ACG (International Classification of Diseases, 9th Revision, Clinical Modification codes 365). Patients were stratified by their sex and age; differences in standardized incidence rates were compared between the stratified groups. RESULTS: Throughout the study period, the prevalence of diagnosed OAG (slope=0.18, P<0.0001) and ACG (slope=0.09, P<0.0001) increased. Before 2005, the prevalence of ACG was higher than that of OAG; however, from 2005 to 2010, the prevalence of OAG was higher than that of ACG. The standardized incidence of diagnosed OAG increased insignificantly (slope=1.06, P=0.18), and that of diagnosed ACG decreased significantly (slope= 1.17, P=0.009). The prevalence and the incidence of OAG and ACG were the highest among people of advanced age. Women had higher standardized incidence rates of ACG during the study period. Men had higher standardized incidence rates of OAG in every year of the study with the exception of 2007. CONCLUSIONS: In Taiwan, ACG was more prevalent in women and OAG might be more prevalent in men. The prevalence of ACG was higher than that of OAG before 2005, but the prevalence of OAG has been higher than that of ACG since 2005. PMID- 26900829 TI - A Systematic Review of End-of-Life Visual Impairment in Open-Angle Glaucoma: An Epidemiological Autopsy. AB - PURPOSE: Glaucoma patients are still at risk of becoming blind. It is of clinical significance to determine the risk of blindness and its causes to prevent its occurrence. This systematic review estimates the number of treated glaucoma patients with end-of-life visual impairment (VI) and blindness and the factors that are associated with this. METHODS: A systematic literature search in relevant databases was conducted in August 2014 on end-of-life VI. A total of 2574 articles were identified, of which 5 on end-of-life VI. Several data items were extracted from the reports and presented in tables. RESULTS: All studies had a retrospective design. A considerable number of glaucoma patients were found to be blind at the end of their life; with up to 24% unilateral and 10% bilateral blindness. The following factors were associated with blindness: (1) baseline severity of visual field loss: advanced stage of glaucoma or substantial visual field loss at the initial visit; (2) factors influencing progression: fluctuation of intraocular pressure (IOP) during treatment, presence of pseudoexfoliation, poor patient compliance, higher IOP; (3) longer time period: longer duration of disease and older age at death because of a longer life expectancy; and (4) coexistence of other ocular pathology. CONCLUSIONS: Further prevention of blindness in glaucoma patients is needed. To reach this goal, it is important to address the risk factors for blindness identified in this review, especially those that can be modified, such as advanced disease at diagnosis, high and fluctuating IOP, and poor compliance. PMID- 26900830 TI - Outcomes of Trabeculectomy With Mitomycin-C in Uveitis Associated With Vogt Koyanagi-Harada Disease. AB - OBJECTIVES: To evaluate the outcomes of trabeculectomy with mitomycin-C (MMC) in uveitis associated with Vogt-Koyanagi-Harada disease (VKH). METHODS: Retrospective cohort study included 27 eyes of 15 patients with uveitic glaucoma associated with VKH disease who underwent trabeculectomy with MMC as a first glaucoma procedure at King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia between 1992 and 2011. The main outcome measures were: the intraocular pressure (IOP), the number of antiglaucoma medications, the presence of visually threatening complications, and the need for further surgeries to control the IOP. RESULTS: The mean follow-up was 78.19 months. The IOP decreased significantly from a mean of 40.15+/-7.0 to 13.12+/-6.9 mm Hg on the last follow-up (P<0.01) as well as during the whole follow-up period. The number of medications needed to control the IOP also decreased significantly from 3.89+/-0.6 to 1.04+/-1.3. The cumulative probabilities of success were 77.8%, 74.1%, 63.0%, and 51.9% at 12, 24, 36, and 48 months postoperatively, respectively. The most common complications were cataract development and progression (53.8%), hypotony (IOP<=5 mm Hg) (33.3%), choroidal effusion (7.4%), and decompressive retinopathy (7.4%). Eight eyes (29.6%) needed a second procedure to control the IOP. CONCLUSIONS: Trabeculectomy with MMC offers an acceptable intermediate term success and IOP control in uveitic glaucoma associated with VKH. However, significant number of eyes needed further procedures to control the pressure. Therefore, continuous monitoring of the pressure is important. PMID- 26900831 TI - In Vivo Confocal Microscopy and Biomicroscopy of Filtering Blebs After Trabeculectomy. AB - PURPOSE: The aim of this study is to analyze filtering blebs (FBs) after trabeculectomy with in vivo confocal microscopy (IVCM) and slit-lamp biomicroscopy. MATERIALS AND METHODS: IVCM using the Heidelberg Retina Tomograph/Rostock Cornea Module and biomicroscopic examination were performed in 67 FBs in 55 patients 3 months to 30 years postoperatively (mean, 3.2 +/- 2.1 y). Although the blebs were evaluated by slit-lamp biomicroscopy, standardized FB classification was used. RESULTS: Of the patients, 9 were female (16.3%) and 46 were male (83.7%), ranging in age from 32 to 81 (51.5 +/- 13.2) years. The absence of vascularization and tortuous vessels and the presence of epithelial microcysts on the bleb were significantly correlated with good bleb function (P=0.001). IVCM findings significantly correlated with good bleb function, including the number of epithelial microcysts (P=0.002), the stromal cysts without capsule (P<0.001), minimal vascularization (P=0.002), and the absence of tortuous conjunctival vessels (P=0.003) and reticular and trabecular bleb patterns (P=0.01 and <0.01, respectively). In contrast, a hyperreflective condensed bleb stroma was significantly associated with bleb failure (P<0.001). CONCLUSIONS: IVCM supports biomicroscopic evaluation as the mainstay for FB analysis and permits diagnostic imaging of FBs to evaluate and follow-up the bleb, differentiation between good and insufficient bleb function, and a microscopic analysis at a cellular level including the structural pattern of the bleb. PMID- 26900832 TI - Repeatability of Spectral Domain Optical Coherence Tomography Measurements in High Myopia. AB - PURPOSE: The purpose of this study was to compare the repeatability of spectral domain optical coherence tomography (SDOCT) parameters in high-myopic and emmetropic healthy subjects, and to evaluate the influence of axial length on the repeatability of SDOCT parameters in high myopia. METHODS: In a prospective study, 93 eyes of 63 high-myopic subjects (spherical refractive error, -6 to -12 D; median age, 25 y) and 28 eyes of 14 emmetropic (spherical refractive error, 0 D; median age, 30 y) subjects underwent optic nerve head, retinal nerve fiber layer (RNFL), and ganglion cell complex imaging with SDOCT. For the repeatability analysis, 31 eyes of 31 high-myopic subjects and 14 eyes of 14 emmetropic subjects underwent 3 repeated scans in the same session. RESULTS: Among the optic nerve head parameters, within-subject coefficient of variation (CVw) measurements of the disc area (0.6% vs. 0.2%), rim area (8.7 vs. 2.8), and rim volume (16.7 vs. 8.9) were significantly larger (worse) in high-myopic compared with the emmetropic subjects. CVw measurements of all RNFL (range, 1.7 to 22.4) and ganglion cell complex (range, 1.8 to 2.5) parameters in high-myopic subjects were comparable to that in emmetropic subjects (2.4 to 24.0 and 1.7 to 2.0, respectively). Axial length significantly affected the CVw of nasal (coefficient, 0.01; P=0.04) and average RNFL (coefficient, 0.004; P=0.001) parameters but not that of the other SDOCT parameters. CONCLUSIONS: Repeatabilities of most of the SDOCT parameters in high-myopic subjects were good and comparable to that of emmetropic subjects. This suggests that SDOCT can be useful for following up high myopic glaucoma patients to detect progression. PMID- 26900833 TI - Regression Analysis of Optical Coherence Tomography Disc Variables for Glaucoma Diagnosis. AB - PURPOSE: To report diagnostic accuracy of optical coherence tomography (OCT) disc variables using both time-domain (TD) and Fourier-domain (FD) OCT, and to improve the use of OCT disc variable measurements for glaucoma diagnosis through regression analyses that adjust for optic disc size and axial length-based magnification error. DESIGN: Observational, cross-sectional. PARTICIPANTS: In total, 180 normal eyes of 112 participants and 180 eyes of 138 participants with perimetric glaucoma from the Advanced Imaging for Glaucoma Study. METHODS: Diagnostic variables evaluated from TD-OCT and FD-OCT were: disc area, rim area, rim volume, optic nerve head volume, vertical cup-to-disc ratio (CDR), and horizontal CDR. These were compared with overall retinal nerve fiber layer thickness and ganglion cell complex. Regression analyses were performed that corrected for optic disc size and axial length. Area-under-receiver-operating curves (AUROC) were used to assess diagnostic accuracy before and after the adjustments. An index based on multiple logistic regression that combined optic disc variables with axial length was also explored with the aim of improving diagnostic accuracy of disc variables. MAIN OUTCOME MEASURE: Comparison of diagnostic accuracy of disc variables, as measured by AUROC. RESULTS: The unadjusted disc variables with the highest diagnostic accuracies were: rim volume for TD-OCT (AUROC=0.864) and vertical CDR (AUROC=0.874) for FD-OCT. Magnification correction significantly worsened diagnostic accuracy for rim variables, and while optic disc size adjustments partially restored diagnostic accuracy, the adjusted AUROCs were still lower. Axial length adjustments to disc variables in the form of multiple logistic regression indices led to a slight but insignificant improvement in diagnostic accuracy. CONCLUSIONS: Our various regression approaches were not able to significantly improve disc-based OCT glaucoma diagnosis. However, disc rim area and vertical CDR had very high diagnostic accuracy, and these disc variables can serve to complement additional OCT measurements for diagnosis of glaucoma. PMID- 26900834 TI - Trends in the Treatment of Metastatic Colon and Rectal Cancer in Elderly Patients. AB - BACKGROUND: Little is known about the use and costs of antineoplastic regimens for elderly patients with metastatic colorectal cancer (mCRC). We report population-based trends over a 10-year period in the treatment, survival, and costs in mCRC patients, stratified by ages 65-74 and 75+. METHODS: We used Surveillance, Epidemiology, and End Results-Medicare data for persons diagnosed with metastatic colon (N=16117) or rectal cancer (N=4008) between 2000 and 2009. We estimated the adjusted percent of patients who received antineoplastic agents, by type, number, and their costs 12 months following diagnosis. We report the percent of patients who received 3 or more of commonly prescribed agents and estimate survival for the 24-month period following diagnosis by age and treatment. RESULTS: The percentage that received 3 or more agents increased from 3% to 73% in colon patients aged 65-74 and from 2% to 53% in patients 75+. Similar increases were observed in rectal patients. Average 1-year costs per patient in 2009 were $106,461 and $102,680 for colon and rectal cancers, respectively, reflecting an increase of 32% and 20%, for patients who received antineoplastic agents. Median survival increased by about 6 and 10 months, respectively, for colon and rectal patients aged 65-74 who received antineoplastic agents, but an improvement of only 1 month of median survival was observed for patients 75+. CONCLUSIONS: Expensive multiple agent regimens are increasingly used in older mCRC patients. For patients aged 64-75 years, these treatments may be associated with several months of additional life, but patients aged 75+ may incur considerable expense without any survival benefit. PMID- 26900835 TI - Avian Influenza Virus and DIVA Strategies. AB - Vaccination is becoming a more acceptable option in the effort to eradicate avian influenza viruses (AIV) from commercial poultry, especially in countries where AIV is endemic. The main concern surrounding this option has been the inability of the conventional serological tests to differentiate antibodies produced due to vaccination from antibodies produced in response to virus infection. In attempts to address this issue, at least six strategies have been formulated, aiming to differentiate infected from vaccinated animals (DIVA), namely (i) sentinel birds, (ii) subunit vaccine, (iii) heterologous neuraminidase (NA), (iv) nonstructural 1 (NS1) protein, (v) matrix 2 ectodomain (M2e) protein, and (vi) haemagglutinin subunit 2 (HA2) glycoprotein. This short review briefly discusses the strengths and limitations of these DIVA strategies, together with the feasibility and practicality of the options as a part of the surveillance program directed toward the eventual eradication of AIV from poultry in countries where highly pathogenic avian influenza is endemic. PMID- 26900836 TI - Carrier gas effects on aluminum-catalyzed nanowire growth. AB - Aluminum-catalyzed silicon nanowire growth under low-pressure chemical vapor deposition conditions requires higher reactor pressures than gold-catalyzed growth, but the reasons for this difference are not well understood. In this study, the effects of reactor pressure and hydrogen partial pressure on silicon nanowire growth using an aluminum catalyst were studied by growing nanowires in hydrogen and hydrogen/nitrogen carrier gas mixtures at different total reactor pressures. Nanowires grown in the nitrogen/hydrogen mixture have faceted catalyst droplet tips, minimal evidence of aluminum diffusion from the tip down the nanowire sidewalls, and significant vapor-solid deposition of silicon on the sidewalls. In comparison, wires grown in pure hydrogen show less well-defined tips, evidence of aluminum diffusion down the nanowire sidewalls at increasing reactor pressures and reduced vapor-solid deposition of silicon on the sidewalls. The results are explained in terms of a model wherein the hydrogen partial pressure plays a critical role in aluminum-catalyzed nanowire growth by controlling hydrogen termination of the silicon nanowire sidewalls. For a given reactor pressure, increased hydrogen partial pressures increase the extent of hydrogen termination of the sidewalls which suppresses SiH4 adsorption thereby reducing vapor-solid deposition of silicon but increases the surface diffusion length of aluminum. Conversely, lower hydrogen partial pressures reduce the hydrogen termination and also increase the extent of SiH4 gas phase decomposition, shifting the nanowire growth window to lower growth temperatures and silane partial pressures. PMID- 26900837 TI - Three Dimensional Collagen Scaffold Promotes Intrinsic Vascularisation for Tissue Engineering Applications. AB - Here, we describe a porous 3-dimensional collagen scaffold material that supports capillary formation in vitro, and promotes vascularization when implanted in vivo. Collagen scaffolds were synthesized from type I bovine collagen and have a uniform pore size of 80 MUm. In vitro, scaffolds seeded with primary human microvascular endothelial cells suspended in human fibrin gel formed CD31 positive capillary-like structures with clear lumens. In vivo, after subcutaneous implantation in mice, cell-free collagen scaffolds were vascularized by host neovessels, whilst a gradual degradation of the scaffold material occurred over 8 weeks. Collagen scaffolds, impregnated with human fibrinogen gel, were implanted subcutaneously inside a chamber enclosing the femoral vessels in rats. Angiogenic sprouts from the femoral vessels invaded throughout the scaffolds and these degraded completely after 4 weeks. Vascular volume of the resulting constructs was greater than the vascular volume of constructs from chambers implanted with fibrinogen gel alone (42.7+/-5.0 MUL in collagen scaffold vs 22.5+/-2.3 MUL in fibrinogen gel alone; p<0.05, n = 7). In the same model, collagen scaffolds seeded with human adipose-derived stem cells (ASCs) produced greater increases in vascular volume than did cell-free collagen scaffolds (42.9+/-4.0 MUL in collagen scaffold with human ASCs vs 25.7+/-1.9 MUL in collagen scaffold alone; p<0.05, n = 4). In summary, these collagen scaffolds are biocompatible and could be used to grow more robust vascularized tissue engineering grafts with improved the survival of implanted cells. Such scaffolds could also be used as an assay model for studies on angiogenesis, 3-dimensional cell culture, and delivery of growth factors and cells in vivo. PMID- 26900838 TI - Apolipoprotein(a) Kringle-IV Type 2 Copy Number Variation Is Associated with Venous Thromboembolism. AB - In addition to the established association between high lipoprotein(a) [Lp(a)] concentrations and coronary artery disease, an association between Lp(a) and venous thromboembolism (VTE) has also been described. Lp(a) is controlled by genetic variants in LPA gene, coding for apolipoprotein(a), including the kringle IV type 2 (KIV-2) size polymorphism. Aim of the study was to investigate the role of LPA gene KIV-2 size polymorphism and single nucleotide polymorphisms (SNPs) (rs1853021, rs1800769, rs3798220, rs10455872) in modulating VTE susceptibility. Five hundred and sixteen patients with VTE without hereditary and acquired thrombophilia and 1117 healthy control subjects, comparable for age and sex, were investigated. LPA KIV-2 polymorphism, rs3798220 and rs10455872 SNPs were genotyped by TaqMan technology. Concerning rs1853021 and rs1800769 SNPs, PCR-RFLP assay was used. LPA KIV-2 repeat number was significantly lower in patients than in controls [median (interquartile range) 11(6-17) vs 15(9-25), p<0.0001]. A significantly higher prevalence of KIV-2 repeat number <=7 was observed in patients than in controls (33.5% vs 15.5%, p<0.0001). KIV-2 repeat number was independently associated with VTE (p = 4.36 x10-9), as evidenced by the general linear model analysis adjusted for transient risk factors. No significant difference in allele frequency for all SNPs investigated was observed. Haplotype analysis showed that LPA haplotypes rather than individual SNPs influenced disease susceptibility. Receiver operating characteristic curves analysis showed that a combined risk prediction model, including KIV-2 size polymorphism and clinical variables, had a higher performance in identifying subjects at VTE risk than a clinical-only model, also separately in men and women. PMID- 26900841 TI - The Fundamental Structure and the Reproduction of Spiral Wave in a Two Dimensional Excitable Lattice. AB - In this paper we have systematically investigated the fundamental structure and the reproduction of spiral wave in a two-dimensional excitable lattice. A periodically rotating spiral wave is introduced as the model to reproduce spiral wave artificially. Interestingly, by using the dominant phase-advanced driving analysis method, the fundamental structure containing the loop structure and the wave propagation paths has been revealed, which can expose the periodically rotating orbit of spiral tip and the charity of spiral wave clearly. Furthermore, the fundamental structure is utilized as the core for artificial spiral wave. Additionally, the appropriate parameter region, in which the artificial spiral wave can be reproduced, is studied. Finally, we discuss the robustness of artificial spiral wave to defects. PMID- 26900842 TI - Source and Size of Emotional and Financial-Related Social Support Network on Physical Activity Behavior Among Older Adults. AB - OBJECTIVE: To examine the association of source of emotional- and financial related social support and size of social support network on physical activity behavior among older adults. METHODS: Data from the 1999-2006 NHANES were used (N = 5616; 60 to 85 yrs). Physical activity and emotional- and financial-related social support were assessed via self-report. RESULTS: Older adults with perceived having emotional social support had a 41% increased odds of meeting physical activity guidelines (OR = 1.41; 95% CI: 1.01-1.97). The only specific sources of social support that were associated with meeting physical activity guidelines was friend emotional support (OR = 1.19; 95% CI: 1.01-1.41) and financial support (OR = 1.28; 95% CI: 1.09-1.49). With regard to size of social support network, a dose-response relationship was observed. Compared with those with 0 close friends, those with 1 to 2, 3 to 4, 5, and 6+ close friends, respectively, had a 1.70-, 2.38-, 2.57-, and 2.71-fold increased odds of meeting physical activity guidelines. There was some evidence of gender- and age-specific associations between social support and physical activity. CONCLUSIONS: Emotional and financial-related social support and size of social support network are associated with higher odds of meeting physical activity guidelines among older adults. PMID- 26900839 TI - Hepatitis C Virus Epidemiology in Djibouti, Somalia, Sudan, and Yemen: Systematic Review and Meta-Analysis. AB - OBJECTIVES: To characterize hepatitis C virus (HCV) epidemiology and assess country-specific population-level HCV prevalence in four countries in the Middle East and North Africa (MENA) region: Djibouti, Somalia, Sudan, and Yemen. METHODS: Reports of HCV prevalence were systematically reviewed as per PRISMA guidelines. Pooled HCV prevalence estimates in different risk populations were conducted when the number of measures per risk category was at least five. RESULTS: We identified 101 prevalence estimates. Pooled HCV antibody prevalence in the general population in Somalia, Sudan and Yemen was 0.9% (95% confidence interval [95%CI]: 0.3%-1.9%), 1.0% (95%CI: 0.3%-1.9%) and 1.9% (95%CI: 1.4% 2.6%), respectively. The only general population study from Djibouti reported a prevalence of 0.3% (CI: 0.2%-0.4%) in blood donors. In high-risk populations (e.g., haemodialysis and haemophilia patients), pooled HCV prevalence was 17.3% (95%CI: 8.6%-28.2%) in Sudan. In Yemen, three studies of haemodialysis patients reported HCV prevalence between 40.0%-62.7%. In intermediate-risk populations (e.g.. healthcare workers, in patients and men who have sex with men), pooled HCV prevalence was 1.7% (95%CI: 0.0%-4.9%) in Somalia and 0.6% (95%CI: 0.4%-0.8%) in Sudan. CONCLUSION: National HCV prevalence in Yemen appears to be higher than in Djibouti, Somalia, and Sudan as well as most other MENA countries; but otherwise prevalence levels in this subregion are comparable to global levels. The high HCV prevalence in patients who have undergone clinical care appears to reflect ongoing transmission in clinical settings. HCV prevalence in people who inject drugs remains unknown. PMID- 26900840 TI - Effects of Varied Housing Density on a Hybrid Mouse Strain Followed for 20 Months. AB - To evaluate the effect of increased housing density in a hybrid mouse strain, we evaluated a panel of physiological and behavioral traits in animals that were housed in groups of 3, 5, 8, or 12, using cages that provide 78.1 in2 of floor space. Such groupings resulted in cage densities that ranged from half to almost twice the density recommended by the Guide for the Care and Use of Laboratory Animals. While previous studies have investigated physiological effects of increased housing density using inbred mouse strains, including C57BL/6J and 129S1/SvImJ, this study tested an F1 hybrid population of C57BL/6J x 129S1/SvImJ for changes resulting from either decreased or increased housing density. Mice were followed until they were 20 months old, a substantially longer duration than has been used in previous density studies. We evaluated mortality, growth, home cage behavior, blood pressure, body composition, clinical plasma chemistries, immune function, and organ weights (heart, kidney, adrenal glands, and testes) as endpoints of chronic stress that may arise from sub-optimal housing conditions. Few statistically different parameters were observed in this study, none of which describe chronic stress and all within normal physiological ranges for research mice, suggesting that this hybrid strain was not adversely affected by housing at twice the density currently recommended. PMID- 26900843 TI - Cell Treatment for Stroke in Type Two Diabetic Rats Improves Vascular Permeability Measured by MRI. AB - Treatment of stroke with bone marrow stromal cells (BMSC) significantly enhances brain remodeling and improves neurological function in non-diabetic stroke rats. Diabetes is a major risk factor for stroke and induces neurovascular changes which may impact stroke therapy. Thus, it is necessary to test our hypothesis that the treatment of stroke with BMSC has therapeutic efficacy in the most common form of diabetes, type 2 diabetes mellitus (T2DM). T2DM was induced in adult male Wistar rats by administration of a high fat diet in combination with a single intraperitoneal injection (35mg/kg) of streptozotocin. These rats were then subjected to 2h of middle cerebral artery occlusion (MCAo). T2DM rats received BMSC (5x106, n = 8) or an equal volume of phosphate-buffered saline (PBS) (n = 8) via tail-vein injection at 3 days after MCAo. MRI was performed one day and then weekly for 5 weeks post MCAo for all rats. Compared with vehicle treated control T2DM rats, BMSC treatment of stroke in T2DM rats significantly (p<0.05) decreased blood-brain barrier disruption starting at 1 week post stroke measured using contrast enhanced T1-weighted imaging with gadopentetate, and reduced cerebral hemorrhagic spots starting at 3 weeks post stroke measured using susceptibility weighted imaging, although BMSC treatment did not reduce the ischemic lesion volumes as demarcated by T2 maps. These MRI measurements were consistent with histological data. Thus, BMSC treatment of stroke in T2DM rats initiated at 3 days after stroke significantly reduced ischemic vascular damage, although BMSC treatment did not change infarction volume in T2DM rats, measured by MRI. PMID- 26900844 TI - DNA Barcoding Green Microalgae Isolated from Neotropical Inland Waters. AB - This study evaluated the feasibility of using the Ribulose Bisphosphate Carboxylase Large subunit gene (rbcL) and the Internal Transcribed Spacers 1 and 2 of the nuclear rDNA (nuITS1 and nuITS2) markers for identifying a very diverse, albeit poorly known group, of green microalgae from neotropical inland waters. Fifty-one freshwater green microalgae strains isolated from Brazil, the largest biodiversity reservoir in the neotropics, were submitted to DNA barcoding. Currently available universal primers for ITS1-5.8S-ITS2 region amplification were sufficient to successfully amplify and sequence 47 (92%) of the samples. On the other hand, new sets of primers had to be designed for rbcL, which allowed 96% of the samples to be sequenced. Thirty-five percent of the strains could be unambiguously identified to the species level based either on nuITS1 or nuITS2 sequences' using barcode gap calculations. nuITS2 Compensatory Base Change (CBC) and ITS1-5.8S-ITS2 region phylogenetic analysis, together with morphological inspection, confirmed the identification accuracy. In contrast, only 6% of the strains could be assigned to the correct species based solely on rbcL sequences. In conclusion, the data presented here indicates that either nuITS1 or nuITS2 are useful markers for DNA barcoding of freshwater green microalgae, with advantage for nuITS2 due to the larger availability of analytical tools and reference barcodes deposited at databases for this marker. PMID- 26900845 TI - Learning of Precise Spike Times with Homeostatic Membrane Potential Dependent Synaptic Plasticity. AB - Precise spatio-temporal patterns of neuronal action potentials underly e.g. sensory representations and control of muscle activities. However, it is not known how the synaptic efficacies in the neuronal networks of the brain adapt such that they can reliably generate spikes at specific points in time. Existing activity-dependent plasticity rules like Spike-Timing-Dependent Plasticity are agnostic to the goal of learning spike times. On the other hand, the existing formal and supervised learning algorithms perform a temporally precise comparison of projected activity with the target, but there is no known biologically plausible implementation of this comparison. Here, we propose a simple and local unsupervised synaptic plasticity mechanism that is derived from the requirement of a balanced membrane potential. Since the relevant signal for synaptic change is the postsynaptic voltage rather than spike times, we call the plasticity rule Membrane Potential Dependent Plasticity (MPDP). Combining our plasticity mechanism with spike after-hyperpolarization causes a sensitivity of synaptic change to pre- and postsynaptic spike times which can reproduce Hebbian spike timing dependent plasticity for inhibitory synapses as was found in experiments. In addition, the sensitivity of MPDP to the time course of the voltage when generating a spike allows MPDP to distinguish between weak (spurious) and strong (teacher) spikes, which therefore provides a neuronal basis for the comparison of actual and target activity. For spatio-temporal input spike patterns our conceptually simple plasticity rule achieves a surprisingly high storage capacity for spike associations. The sensitivity of the MPDP to the subthreshold membrane potential during training allows robust memory retrieval after learning even in the presence of activity corrupted by noise. We propose that MPDP represents a biophysically plausible mechanism to learn temporal target activity patterns. PMID- 26900846 TI - Determinant Factors of Untreated Dental Caries and Lesion Activity in Preschool Children Using ICDAS. AB - The aim of the present study was to investigate determinant factors associated with the presence of dental caries and lesion activity in preschool children. A population-based, cross-sectional study was carried out with 843 children of aged three to five years enrolled at public and private preschools in the city of Campina Grande, Brazil. A questionnaire addressing socio-demographic data and oral health care was self-administered by parents/caregivers. Three dentists previously calibrated examined the children for the diagnosis of dental caries and lesion activity using the International Caries Detection and Assessment System (ICDAS). Nutritional status was evaluated based on the body mass index. Logistic regression analysis for complex samples was performed (alpha = 5%). The prevalence of dental caries was 66.3%. Among the children with caries, 88.0% had active lesions. Dental caries was more prevalent in girls (OR = 1.53, 95%CI: 1.05 2.23), in children from families with a monthly household income <=US$312.50 (OR = 2.38, 95%CI: 1.65-3.43) and those whose mothers had up to eight years of schooling (OR = 1.55, 95%CI: 1.07-2.23). Lesion activity was significantly associated with mother's schooling <= 8 years (OR = 2.15, 95%CI: 1.15-4.00). The prevalence rates of dental caries and lesion activity were high and mainly associated with a lower socioeconomic status and mother's schooling. PMID- 26900847 TI - Factors Related to Social Support in Neurological and Mental Disorders. AB - Despite the huge body of research on social support, literature has been primarily focused on its beneficial role for both physical and mental health. It is still unclear why people with mental and neurological disorders experience low levels of social support. The main objective of this study was to explore what are the strongest factors related to social support and how do they interact with each other in neuropsychiatric disorders. The study used cross-sectional data from 722 persons suffering from dementia, depression, epilepsy, migraine, multiple sclerosis, Parkinson's disease, schizophrenia, stroke, and substance use disorders. Multiple linear regressions showed that disability was the strongest factor for social support. Extraversion and agreeableness were significant personality variables, but when the interaction terms between personality traits and disability were included, disability remained the only significant variable. Moreover, level of disability mediated the relationship between personality (extraversion and agreeableness) and level of social support. Moderation analysis revealed that people that had mental disorders experienced lower levels of support when being highly disabled compared to people with neurological disorders. Unlike previous literature, focused on increasing social support as the origin of improving disability, this study suggested that interventions improving day-to-day functioning or maladaptive personality styles might also have an effect on the way people perceive social support. Future longitudinal research, however, is warranted to explore causality. PMID- 26900848 TI - Comparative Transcriptomic Analysis of Primary Duck Hepatocytes Provides Insight into Differential Susceptibility to DHBV Infection. AB - Primary duck hepatocytes (PDH) displays differential susceptibility to duck hepatitis B virus when maintained in the media supplemented with fetal bovine serum or dimethyl sulfoxide (DMSO) which has been widely used for the maintenance of hepatocytes, and prolonging susceptibility to hepadnavirus. However the mechanism underlying maintenance of susceptibility to hepadnavirus by DMSO treatment remains unclear. In this study, a global transcriptome analysis of PDHs under different culture conditions was conducted for investigating the effects of DMSO on maintenance of susceptibility of PDH to DHBV in vitro. The 384 differential expressed genes (DEGs) were identified by comparisons between each library pair (PDHs cultured with or without DMSO or fresh isolated PDH). We analyzed canonical pathways in which the DEGs were enriched in Hepatic Fibrosis / Hepatic Stellate Cell Activation, Bile Acid Biosynthesis and Tight Junction signaling. After re-annotation against human genome data, the 384 DEGs were pooled together with proteins belonging to hepatitis B pathway to construct a protein-protein interaction network. The combination of decreased expression of liver-specific genes (CYP3A4, CYP1E1, CFI, RELN and GSTA1 et al) with increased expression of hepatocyte-dedifferentiation-associated genes (PLA2G4A and PLCG1) suggested that in vitro culture conditions results in the fading of hepatocyte phenotype in PDHs. The expression of seven DEGs associated with tight junction formation (JAM3, PPP2R2B, PRKAR1B, PPP2R2C, MAGI2, ACTA2 and ACTG2) was up regulated after short-term culture in vitro, which was attenuated in the presence of DMSO. Those results could shed light on DHBV infection associated molecular events affected by DMSO. PMID- 26900849 TI - Characterization of Three New Glutaredoxin Genes in the Arbuscular Mycorrhizal Fungus Rhizophagus irregularis: Putative Role of RiGRX4 and RiGRX5 in Iron Homeostasis. AB - Glutaredoxins (GRXs) are small ubiquitous oxidoreductases involved in the regulation of the redox state in living cells. In an attempt to identify the full complement of GRXs in the arbuscular mycorrhizal (AM) fungus Rhizophagus irregularis, three additional GRX homologs, besides the formerly characterized GintGRX1 (renamed here as RiGRX1), were identified. The three new GRXs (RiGRX4, RiGRX5 and RiGRX6) contain the CXXS domain of monothiol GRXs, but whereas RiGRX4 and RiGRX5 belong to class II GRXs, RiGRX6 belongs to class I together with RiGRX1. By using a yeast expression system, we observed that the newly identified homologs partially reverted sensitivity of the GRX deletion yeast strains to external oxidants. Furthermore, our results indicated that RiGRX4 and RiGRX5 play a role in iron homeostasis in yeast. Gene expression analyses revealed that RiGRX1 and RiGRX6 were more highly expressed in the intraradical (IRM) than in the extraradical mycelium (ERM). Exposure of the ERM to hydrogen peroxide induced up-regulation of RiGRX1, RiGRX4 and RiGRX5 gene expression. RiGRX4 expression was also up-regulated in the ERM when the fungus was grown in media supplemented with a high iron concentration. These data indicate the two monothiol class II GRXs, RiGRX4 and RiGRX5, might be involved in oxidative stress protection and in the regulation of fungal iron homeostasis. Increased expression of RiGRX1 and RiGRX6 in the IRM suggests that these GRXs should play a key role in oxidative stress protection of R. irregularis during its in planta phase. PMID- 26900850 TI - N-Terminal-Based Targeted, Inducible Protein Degradation in Escherichia coli. AB - Dynamically altering protein concentration is a central activity in synthetic biology. While many tools are available to modulate protein concentration by altering protein synthesis rate, methods for decreasing protein concentration by inactivation or degradation rate are just being realized. Altering protein synthesis rates can quickly increase the concentration of a protein but not decrease, as residual protein will remain for a while. Inducible, targeted protein degradation is an attractive option and some tools have been introduced for higher organisms and bacteria. Current bacterial tools rely on C-terminal fusions, so we have developed an N-terminal fusion (Ntag) strategy to increase the possible proteins that can be targeted. We demonstrate Ntag dependent degradation of mCherry and beta-galactosidase and reconfigure the Ntag system to perform dynamic, exogenously inducible degradation of a targeted protein and complement protein depletion by traditional synthesis repression. Model driven analysis that focused on rates, rather than concentrations, was critical to understanding and engineering the system. We expect this tool and our model to enable inducible protein degradation use particularly in metabolic engineering, biological study of essential proteins, and protein circuits. PMID- 26900851 TI - Specific Neuropilins Expression in Alveolar Macrophages among Tissue-Specific Macrophages. AB - In the immune system, neuropilins (NRPs), including NRP-1 and NRP-2, are expressed in thymocytes, dendritic cells, regulatory T cells and macrophages. Their functions on immune cells around the neoplastic cells vary into pro angiogenesis, tumor progression and anti-angiogenesis according to their ligands. Even though NRPs expression on malignant tumors and immune system has studied, a PubMed-based literature query did not yield any articles describing NRPs expression on tissue-specific macrophages. The aims of this study were (i) to detect NRPs expression on tissue-specific macrophages in the brain, liver, spleen, lymph node and lung; (ii) to observe NRPs expression in classes of macrophages, including alveolar macrophages (AMs), bronchial macrophages (BMs), interstitial macrophages (IMs), intravascular macrophages (IVMs) and macrophage subsets (M1, M2 and Mox) in lung; and (iii) to detect the co-expression of NRPs and dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) in AMs. Both NRPs were specifically detected in AMs among tissue-specific macrophages by immunohistochemistry (IHC). NRPs mRNA expression levels were characterized in normal lung by reverse transcriptase polymerase chain reaction (RT-PCR) and in situ-polymerase chain reaction (in situ-PCR). The expression of both NRPs was detected in AMs, BMs and IVMs by IHC. The frequency of NRPs+ AMs in lung tissue adjacent to the cancer margin was significantly higher than the frequencies in inflamed and normal lung tissue. Double and triple IHC demonstrated that NRPs are expressed on all macrophage subsets in lung. Double IHC showed co-expression of DC-SIGN and NRPs in AMs. This study demonstrated for the first time the specific expression of both NRPs in AMs among tissue-specific macrophages and their expression on M1, M2 and Mox macrophages. Furthermore, the possible origin of AMs from blood monocytes could be suggested from a co-expression of NRPs and DC-SIGN. PMID- 26900853 TI - Blood Group Antigens C, Lub and P1 May Have a Role in HIV Infection in Africans. AB - BACKGROUND: Botswana is among the world's countries with the highest rates of HIV infection. It is not known whether or not this susceptibility to infection is due to genetic factors in the population. Accumulating evidence, however, points to the role of erythrocytes as potential mediators of infection. We therefore sought to establish the role, if any, of some erythrocyte antigens in HIV infection in a cross-section of the population. METHODS: 348 (346 HIV-negative and 2 HIV positive) samples were obtained from the National Blood Transfusion Service as residual samples, while 194 HIV-positive samples were obtained from the Botswana Harvard HIV Reference Laboratory. Samples were grouped for twenty three antigens. Chi-square or Fischer Exact analyses were used to compare the frequencies of the antigens in the two groups. A stepwise, binary logistic regression was used to study the interaction of the various antigens in the light of HIV-status. RESULTS: The Rh antigens C and E were associated with HIV-negative status, while blood group Jka, P1 and Lub were associated with HIV-positive status. A stepwise binary logistic regression analysis yielded group C as the most significant protective blood group while Lub and P1 were associated with significantly higher odds ratio in favor of HIV-infection. The lower-risk-associated group C was significantly lower in Africans compared to published data for Caucasians and might partially explain the difference in susceptibility to HIV-1. CONCLUSION: The most influential antigen C, which also appears to be protective, is significantly lower in Africans than published data for Caucasians or Asians. On the other hand, there appear to be multiple antigens associated with increased risk that may override the protective role of C. A study of the distribution of these antigens in other populations may shed light on their roles in the HIV pandemic. PMID- 26900852 TI - In Vivo Screening Using Transgenic Zebrafish Embryos Reveals New Effects of HDAC Inhibitors Trichostatin A and Valproic Acid on Organogenesis. AB - The effects of endocrine disrupting chemicals (EDCs) on reproduction are well known, whereas their developmental effects are much less characterized. However, exposure to endocrine disruptors during organogenesis may lead to deleterious and permanent problems later in life. Zebrafish (Danio rerio) transgenic lines expressing the green fluorescent protein (GFP) in specific organs and tissues are powerful tools to uncover developmental defects elicited by EDCs. Here, we used seven transgenic lines to visualize in vivo whether a series of EDCs and other pharmaceutical compounds can alter organogenesis in zebrafish. We used transgenic lines expressing GFP in pancreas, liver, blood vessels, inner ear, nervous system, pharyngeal tooth and pectoral fins. This screen revealed that four of the tested chemicals have detectable effects on different organs, which shows that the range of effects elicited by EDCs is wider than anticipated. The endocrine disruptor tetrabromobisphenol-A (TBBPA), as well as the three drugs diclofenac, trichostatin A (TSA) and valproic acid (VPA) induced abnormalities in the embryonic vascular system of zebrafish. Moreover, TSA and VPA induced specific alterations during the development of pancreas, an observation that was confirmed by in situ hybridization with specific markers. Developmental delays were also induced by TSA and VPA in the liver and in pharyngeal teeth, resulting in smaller organ size. Our results show that EDCs can induce a large range of developmental alterations during embryogenesis of zebrafish and establish GFP transgenic lines as powerful tools to screen for EDCs effects in vivo. PMID- 26900854 TI - Surfactant Protein-D Is Essential for Immunity to Helminth Infection. AB - Pulmonary epithelial cell responses can enhance type 2 immunity and contribute to control of nematode infections. An important epithelial product is the collectin Surfactant Protein D (SP-D). We found that SP-D concentrations increased in the lung following Nippostrongylus brasiliensis infection; this increase was dependent on key components of the type 2 immune response. We carried out loss and gain of function studies of SP-D to establish if SP-D was required for optimal immunity to the parasite. N. brasiliensis infection of SP-D-/- mice resulted in profound impairment of host innate immunity and ability to resolve infection. Raising pulmonary SP-D levels prior to infection enhanced parasite expulsion and type 2 immune responses, including increased numbers of IL-13 producing type 2 innate lymphoid cells (ILC2), elevated expression of markers of alternative activation by alveolar macrophages (alvM) and increased production of the type 2 cytokines IL-4 and IL-13. Adoptive transfer of alvM from SP-D-treated parasite infected mice into naive recipients enhanced immunity to N. brasiliensis. Protection was associated with selective binding by the SP-D carbohydrate recognition domain (CRD) to L4 parasites to enhance their killing by alvM. These findings are the first demonstration that the collectin SP-D is an essential component of host innate immunity to helminths. PMID- 26900855 TI - Dog Demography, Animal Bite Management and Rabies Knowledge-Attitude and Practices in the Awash Basin, Eastern Ethiopia. AB - BACKGROUND: Rabies is a viral zoonosis that has been described in limited numbers of studies in Ethiopia at large and among pastoralists in particular. This study assessed dog demography, bite wound prevalence and management, potential risk factors of disease transmission and knowledge attitude practice towards rabies among urban dwellers, pastoralists and health workers in Awash, Eastern Ethiopia. METHODOLOGY: Information was collected by means of structured questionnaires and interviews and through medical and official records from the Agricultural and Health bureaus. PRINCIPAL FINDINGS: Respondents totaled 539 (471 urban, 49 pastoralists, 19 medical). Dog(s) were owned in 33% urban and 75.5% pastoralist households respectively. Mean dog number per dog owning household was 1.50 (95%CI: 1.40-1.60) in urban and 2.05 (95%CI: 1.51-2.60) in pastoralists sites. Human Dog Ratio in Metahara was 4.7:1. No bite wounds records were kept in medical facilities, where staff recalled around 100 bites per year, 2/3 being in adults. Over 90% of the respondents claimed knowing rabies but up to 79.2% pastoralist did not know how dogs acquire the disease; 37.3% urban and 23% pastoralist did not know the symptoms of rabies in dogs; 36% urban and 44% pastoralists did not know rabies symptoms in people. Eighty percent of pastoralists did not know that the disease was fatal in people if untreated. Over half (58.7%) of pastoralist respondents go to traditional healers if bitten, despite a health extension worker program in place in the study area. Knowledge gaps were also shown amidst medical staff. CONCLUSIONS: The study highlighted overall poor disease knowledge, severe under-reporting of human rabies cases, lack of record keeping and poor collaboration between the public and animal health sectors and communities in rabies control. PMID- 26900856 TI - Model-Driven Understanding of Palmitoylation Dynamics: Regulated Acylation of the Endoplasmic Reticulum Chaperone Calnexin. AB - Cellular functions are largely regulated by reversible post-translational modifications of proteins which act as switches. Amongst these, S-palmitoylation is unique in that it confers hydrophobicity. Due to technical difficulties, the understanding of this modification has lagged behind. To investigate principles underlying dynamics and regulation of palmitoylation, we have here studied a key cellular protein, the ER chaperone calnexin, which requires dual palmitoylation for function. Apprehending the complex inter-conversion between single-, double- and non-palmitoylated species required combining experimental determination of kinetic parameters with extensive mathematical modelling. We found that calnexin, due to the presence of two cooperative sites, becomes stably acylated, which not only confers function but also a remarkable increase in stability. Unexpectedly, stochastic simulations revealed that palmitoylation does not occur soon after synthesis, but many hours later. This prediction guided us to find that phosphorylation actively delays calnexin palmitoylation in resting cells. Altogether this study reveals that cells synthesize 5 times more calnexin than needed under resting condition, most of which is degraded. This unused pool can be mobilized by preventing phosphorylation or increasing the activity of the palmitoyltransferase DHHC6. PMID- 26900857 TI - Happier People Show Greater Neural Connectivity during Negative Self-Referential Processing. AB - Life satisfaction is an essential component of subjective well-being and provides a fundamental resource for optimal everyday functioning. The goal of the present study was to examine how life satisfaction influences self-referential processing of emotionally valenced stimuli. Nineteen individuals with high life satisfaction (HLS) and 21 individuals with low life satisfaction (LLS) were scanned using functional MRI while performing a face-word relevance rating task, which consisted of 3 types of face stimuli (self, public other, and unfamiliar other) and 3 types of word stimuli (positive, negative, and neutral). We found a significant group x word valence interaction effect, most strikingly in the dorsal medial prefrontal cortex. In the positive word condition dorsal medial prefrontal cortex activity was significantly higher in the LLS group, whereas in the negative word condition it was significantly higher in the HLS group. The two groups showed distinct functional connectivity of the dorsal medial prefrontal cortex with emotional processing-related regions. The findings suggest that, in response to emotional stimuli, individuals with HLS may successfully recruit emotion regulation-related regions in contrast to individuals with LLS. The difference in functional connectivity during self-referential processing may lead to an influence of life satisfaction on responses to emotion-eliciting stimuli. PMID- 26900859 TI - Complete Genome Sequence and Comparative Genomics of a Novel Myxobacterium Myxococcus hansupus. AB - Myxobacteria, a group of Gram-negative aerobes, belong to the class delta proteobacteria and order Myxococcales. Unlike anaerobic delta-proteobacteria, they exhibit several unusual physiogenomic properties like gliding motility, desiccation-resistant myxospores and large genomes with high coding density. Here we report a 9.5 Mbp complete genome of Myxococcus hansupus that encodes 7,753 proteins. Phylogenomic and genome-genome distance based analysis suggest that Myxococcus hansupus is a novel member of the genus Myxococcus. Comparative genome analysis with other members of the genus Myxococcus was performed to explore their genome diversity. The variation in number of unique proteins observed across different species is suggestive of diversity at the genus level while the overrepresentation of several Pfam families indicates the extent and mode of genome expansion as compared to non-Myxococcales delta-proteobacteria. PMID- 26900860 TI - State-of-the-Art Analysis of High-Frequency (Gamma Range) Electroencephalography in Humans. AB - Gamma oscillations (>30 Hz) in the brain are involved in attention, perception and memory. They are altered in various pathological states, as well as by neuropharmaceuticals, so that they are of interest in drug and clinical investigations. However, when the human electroencephalogram is recorded on the scalp, this neural high-frequency signal is buried under a range of other electrical signals such that, without careful handling, recordings of the high frequency electroencephalogram cannot be considered reliable. The artefacts of concern originate from: power line noise, saccade-associated contraction of the extra-ocular muscles, activity of muscles in the scalp, face and neck, screen refresh artefacts and activity of the muscles associated with blinking. Recent progress in dealing with these artefacts is described, including either noise cancellation or phased noise template subtraction for power line noise, regression or independent component analysis for correcting extra-ocular muscle activity and mathematical modelling for reducing scalp, face and neck muscle activity. If the artefacts are properly addressed, the neural gamma signal can be uncovered. PMID- 26900858 TI - Continuous AMD3100 Treatment Worsens Renal Fibrosis through Regulation of Bone Marrow Derived Pro-Angiogenic Cells Homing and T-Cell-Related Inflammation. AB - AMD3100 is a small molecule inhibitor of chemokine receptor type 4 (CXCR4), which is located in the cell membranes of CD34+ cells and a variety of inflammatory cells and has been reported to reduce organ fibrosis in the lung, liver and myocardium. However, the effect of AMD3100 on renal fibrosis is unknown. This study investigated the impact of AMD3100 on renal fibrosis. C57bl/6 mice were subjected to unilateral ureteral obstruction (UUO) surgery with or without AMD3100 administration. Tubular injury, collagen deposition and fibrosis were detected and analyzed by histological staining, immunocytochemistry and Western Blot. Bone marrow derived pro-angiogenic cells (CD45+, CD34+ and CD309+ cells) and capillary density (CD31+) were measured by flow cytometry (FACS) and immunofluorescence (IF). Inflammatory cells, chemotactic factors and T cell proliferation were characterized. We found that AMD3100 treatment did not alleviate renal fibrosis but, rather, increased tissue damage and renal fibrosis. Continuous AMD3100 administration did not improve bone marrow derived pro angiogenic cells mobilization but, rather, inhibited the migration of bone marrow derived pro-angiogenic cells into the fibrotic kidney. Additionally, T cell infiltration was significantly increased in AMD3100-treated kidneys compared to un-treated kidneys. Thus, treatment of UUO mice with AMD3100 led to an increase in T cell infiltration, suggesting that AMD3100 aggravated renal fibrosis. PMID- 26900862 TI - Cytogenetic Characterization of the TM4 Mouse Sertoli Cell Line. II. Chromosome Microdissection, FISH, Scanning Electron Microscopy, and Confocal Laser Scanning Microscopy. AB - The chromosomes and interphase cell nuclei of the permanent mouse Sertoli cell line TM4 were examined by chromosome microdissection, FISH, scanning electron microscopy, and confocal laser scanning microscopy. The already known marker chromosomes m1-m5 were confirmed, and 2 new large marker chromosomes m6 and m7 were characterized. The minute heterochromatic marker chromosomes m4 and m5 were microdissected and their DNA amplified by DOP-PCR. FISH of this DNA probe on TM4 metaphase chromosomes demonstrated that the m4 and m5 marker chromosomes have derived from the centromeric regions of normal telocentric mouse chromosomes. Ectopic pairing of the m4 and m5 marker chromosomes with the centromeric region of any of the other chromosomes (centromeric associations) was apparent in ~60% of the metaphases. Scanning electron microscopy revealed DNA-protein bridges connecting the centromeric regions of normal chromosomes and the associated m4 and m5 marker chromosomes. Interphase cell nuclei of TM4 Sertoli cells did not exhibit the characteristic morphology of Sertoli cells in the testes of adult mice as shown by fluorescence microscopy and confocal laser scanning microscopy. PMID- 26900863 TI - Nanotopography Promotes Pancreatic Differentiation of Human Embryonic Stem Cells and Induced Pluripotent Stem Cells. AB - Although previous studies suggest that nanotopographical features influence properties and behaviors of stem cells, only a few studies have attempted to derive clinically useful somatic cells from human pluripotent stem cells using nanopatterned surfaces. In the present study, we report that polystyrene nanopore patterned surfaces significantly promote the pancreatic differentiation of human embryonic and induced pluripotent stem cells. We compared different diameters of nanopores and showed that 200 nm nanopore-patterned surfaces highly upregulated the expression of PDX1, a critical transcription factor for pancreatic development, leading to an approximately 3-fold increase in the percentage of differentiating PDX1(+) pancreatic progenitors compared with control flat surfaces. Furthermore, in the presence of biochemical factors, 200 nm nanopore patterned surfaces profoundly enhanced the derivation of pancreatic endocrine cells producing insulin, glucagon, or somatostatin. We also demonstrate that nanopore-patterned surface-induced upregulation of PDX1 is associated with downregulation of TAZ, suggesting the potential role of TAZ in nanopore-patterned surface-mediated mechanotransduction. Our study suggests that appropriate cytokine treatments combined with nanotopographical stimulation could be a powerful tool for deriving a high purity of desired cells from human pluripotent stem cells. PMID- 26900864 TI - Host-pathogen interactions: A cholera surveillance system. PMID- 26900865 TI - Chemoproteomic profiling of host and pathogen enzymes active in cholera. AB - Activity-based protein profiling (ABPP) is a chemoproteomic tool for detecting active enzymes in complex biological systems. We used ABPP to identify secreted bacterial and host serine hydrolases that are active in animals infected with the cholera pathogen Vibrio cholerae. Four V. cholerae proteases were consistently active in infected rabbits, and one, VC0157 (renamed IvaP), was also active in human choleric stool. Inactivation of IvaP influenced the activity of other secreted V. cholerae and rabbit enzymes in vivo, and genetic disruption of all four proteases increased the abundance of intelectin, an intestinal lectin, and its binding to V. cholerae in infected rabbits. Intelectin also bound to other enteric bacterial pathogens, suggesting that it may constitute a previously unrecognized mechanism of bacterial surveillance in the intestine that is inhibited by pathogen-secreted proteases. Our work demonstrates the power of activity-based proteomics to reveal host-pathogen enzymatic dialog in an animal model of infection. PMID- 26900868 TI - Meaning Making in the Context of Disasters. AB - OBJECTIVE: Understanding the factors underlying adaptive psychological responses and recovery after disasters has important implications for intervention and prevention efforts. To date, little attention has been paid to successful coping processes in recovering from natural and technological disasters. This article takes a meaning making perspective to explicate how survivors successfully adapt after disasters. METHOD: Relevant literature is reviewed to illustrate the process of adaptation and resilience after disasters. RESULTS: Studies to date suggest both survivors' global meaning, particularly their religiousness and sense of meaning, and their appraisals and meaning making after the disaster are important influences on their postdisaster resilience. Meanings made in the form of changes in global beliefs and perceived growth have been reported and shown to have inconsistent relations with adjustment. CONCLUSIONS: Although much more research is needed, current literature suggests that meaning making processes are central to recovery and resilience after a range of disasters. PMID- 26900866 TI - Autopalmitoylation of TEAD proteins regulates transcriptional output of the Hippo pathway. AB - TEA domain (TEAD) transcription factors bind to the coactivators YAP and TAZ and regulate the transcriptional output of the Hippo pathway, playing critical roles in organ size control and tumorigenesis. Protein S-palmitoylation attaches a fatty acid, palmitate, to cysteine residues and regulates protein trafficking, membrane localization and signaling activities. Using activity-based chemical probes, we discovered that human TEADs possess intrinsic palmitoylating enzyme like activities and undergo autopalmitoylation at evolutionarily conserved cysteine residues under physiological conditions. We determined the crystal structures of lipid-bound TEADs and found that the lipid chain of palmitate inserts into a conserved deep hydrophobic pocket. Strikingly, palmitoylation did not alter TEAD's localization, but it was required for TEAD's binding to YAP and TAZ and was dispensable for its binding to the Vgll4 tumor suppressor. Moreover, palmitoylation-deficient TEAD mutants impaired TAZ-mediated muscle differentiation in vitro and tissue overgrowth mediated by the Drosophila YAP homolog Yorkie in vivo. Our study directly links autopalmitoylation to the transcriptional regulation of the Hippo pathway. PMID- 26900867 TI - Pooled screening for antiproliferative inhibitors of protein-protein interactions. AB - Protein-protein interactions (PPIs) are emerging as a promising new class of drug targets. Here, we present a novel high-throughput approach to screen inhibitors of PPIs in cells. We designed a library of 50,000 human peptide-binding motifs and used a pooled lentiviral system to express them intracellularly and screen for their effects on cell proliferation. We thereby identified inhibitors that drastically reduced the viability of a pancreatic cancer line (RWP1) while leaving a control line virtually unaffected. We identified their target interactions computationally, and validated a subset in experiments. We also discovered their potential mechanisms of action, including apoptosis and cell cycle arrest. Finally, we confirmed that synthetic lipopeptide versions of our inhibitors have similarly specific and dosage-dependent effects on cancer cell growth. Our screen reveals new drug targets and peptide drug leads, and it provides a rich data set covering phenotypes for the inhibition of thousands of interactions. PMID- 26900869 TI - Peri-implantitis - onset and pattern of progression. AB - BACKGROUND: While information on the prevalence of peri-implantitis is available, data describing onset and progression of the disease are limited. MATERIAL & METHODS: A 9-year follow-up examination of 596 randomly selected implant-carrying individuals identified 62 patients with moderate/severe peri-implantitis. Longitudinal assessments of peri-implant marginal bone levels were used to construct a statistical model with bone loss as the dependent variable. A multilevel growth model estimated the pattern of bone loss for each implant/patient. Onset of peri-implantitis was determined by evaluating the cumulative percentage of implants/patients presenting with estimated bone loss at each year following prosthesis delivery. RESULTS: The analysis showed a non linear, accelerating pattern of bone loss at the 105 affected implants. The onset of peri-implantitis occurred early, and 52% and 66% of implants presented with bone loss of >0.5 mm at years 2 and 3 respectively. A total of 70% and 81% of subjects presented with >=1 implants with bone loss of >0.5 mm at years 2 and 3 respectively. CONCLUSIONS: It is suggested that peri-implantitis progresses in a non-linear, accelerating pattern and that, for the majority of cases, the onset occurs within 3 years of function. PMID- 26900870 TI - Two-Component Polymeric Materials of Fullerenes and the Transition Metal Complexes: A Bridge between Metal-Organic Frameworks and Conducting Polymers. AB - In this review, we examined the interactions of metal complexes and metal surfaces with fullerenes. That information has been related to the formation of redox-active materials produced by electrochemical reduction of solutions of various transition metal complexes and fullerene or fullerene adducts. These redox-active polymers are strongly bound to electrode surfaces and display electrochemical activity in solutions containing only supporting electrolyte. Extensive studies of the electrochemical behavior of these films have been used to characterize their properties and structure. The process that produces these poly-Pd(n)C60 and poly-Pt(n)C60 films can also produce composite materials that consist of metal nanoparticles interspersed with the poly-Pd(n)C60 and poly Pt(n)C60 materials. The relationship between these redox-active films and conducting metal organic framework materials has been examined. These insoluble, redox-active polymers have potential utility for the adsorption of various gases, for the construction of capacitors, for sensing, for the preparation of metal containing heterofullerenes, and for catalysis. PMID- 26900872 TI - Convex optimized diffusion encoding (CODE) gradient waveforms for minimum echo time and bulk motion-compensated diffusion-weighted MRI. AB - PURPOSE: To evaluate convex optimized diffusion encoding (CODE) gradient waveforms for minimum echo time and bulk motion-compensated diffusion-weighted imaging (DWI). METHODS: Diffusion-encoding gradient waveforms were designed for a range of b-values and spatial resolutions with and without motion compensation using the CODE framework. CODE, first moment (M1 ) nulled CODE-M1 , and first and second moment (M2 ) nulled CODE-M1 M2 were used to acquire neuro, liver, and cardiac ADC maps in healthy subjects (n=10) that were compared respectively to monopolar (MONO), BIPOLAR (M1 = 0), and motion-compensated (MOCO, M1 + M2 = 0) diffusion encoding. RESULTS: CODE significantly improved the SNR of neuro ADC maps compared with MONO (19.5 +/- 2.5 versus 14.5 +/- 1.9). CODE-M1 liver ADCs were significantly lower (1.3 +/- 0.1 versus 1.8 +/- 0.3 * 10-3 mm2 /s, ie, less motion corrupted) and more spatially uniform (6% versus 55% ROI difference) than MONO and had higher SNR than BIPOLAR (SNR = 14.9 +/- 5.3 versus 8.0 +/- 3.1). CODE-M1 M2 cardiac ADCs were significantly lower than MONO (1.9 +/- 0.6 versus 3.8 +/- 0.3 x10-3 mm2 /s) throughout the cardiac cycle and had higher SNR than MOCO at systole (9.1 +/- 3.9 versus 7.0 +/- 2.6) while reporting similar ADCs (1.5 +/- 0.2 versus 1.4 +/- 0.6 * 10-3 mm2 /s). CONCLUSIONS: CODE significantly improved SNR for ADC mapping in the brain, liver and heart, and significantly improved DWI bulk motion robustness in the liver and heart. Magn Reson Med 77:717 729, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 26900873 TI - Need assessment of enhancing the weightage of applied biochemistry in the undergraduate curriculum at MGIMS, sevagram. AB - In order to review the need assessment of enhancing the weightage of Applied Biochemistry in the undergraduate curriculum at Mahatma Gandhi Institute of Medical Sciences (MGIMS), Sevagram, a validated questionnaire was sent to 453 participants which include 387 undergraduate students, 11 interns, 23 postgraduate students, and 32 faculty members. A web-based data collection and analysis tool was designed for online questionnaire distribution, data collection, and analysis. Response rate was 100%. Most of the respondents agreed that the subject Biochemistry has relevance in clinical practice (81.24%) and applied based learning of Biochemistry by medical undergraduates would help in overall improvement in the health standards/patients care (83.44%). According to 65.12% respondents, most of the medical undergraduates read Biochemistry just for examination purpose only. Nearly half of the respondents agreed that minute details of biochemical reactions were not much useful in clinical practice (53.86%) and the vast majority of diagrammatic cycles memorized by the medical undergraduates had no relevance in clinical practice (51.21%), the decreased interest in learning the Applied Biochemistry was due to more amount of clinically irrelevant information taught to medical undergraduates (73.51%), there was a need to rethink for removing the diagrammatic biochemical cycles from curriculum for medical undergraduates (48.12%), the less learning of Applied Biochemistry or competencies would affect the clinical skills and knowledge of medical undergraduates (70.42%). The result of this study suggests that there is need for restructuring the Biochemistry curriculum with more clinical relevance. (c) 2016 by The International Union of Biochemistry and Molecular Biology, 44:230 240, 2016. PMID- 26900871 TI - Cerebellar brain inhibition in the target and surround muscles during voluntary tonic activation. AB - Motor surround inhibition is the neural mechanism that selectively favours the contraction of target muscles and inhibits nearby muscles to prevent unwanted movements. This inhibition was previously reported at the onset of a movement, but not during a tonic contraction. Cerebellar brain inhibition (CBI) is reduced in active muscles during tonic activation; however, it has not been studied in the surround muscles. CBI was evaluated in the first dorsal interosseus (FDI) muscle as the target muscle, and the abductor digiti minimi, flexor carpi radialis and extensor carpi radialis muscles as surround muscles, during rest and tonic activation of the FDI muscle in 21 subjects. Cerebellar stimulation was performed under magnetic resonance imaging-guided neuronavigation targeting lobule VIII of the cerebellar hemisphere. Stimulus intensities for cerebellar stimulation were based on the resting motor cortex threshold (RMT) and adjusted for the depth difference between the cerebellar and motor cortices. We used 90 120% of the adjusted RMT as the conditioning stimulus intensity during rest. The intensity that generated the best CBI at rest in the FDI muscle was selected for use during tonic activation. During selective tonic activation of the FDI muscle, CBI was significantly reduced only for the FDI muscle, and not for the surround muscles. Unconditioned motor evoked potential sizes were increased in all muscles during FDI muscle tonic activation as compared with rest, despite background electromyography activity increasing only for the FDI muscle. Our study suggests that the cerebellum may play an important role in selective tonic finger movement by reducing its inhibition in the motor cortex only for the relevant agonist muscle. PMID- 26900874 TI - Sepsis: the need for tolerance not complacency. AB - Sepsis is a life-threatening condition that arises as a systemic inflammatory response syndrome to an infection. Its uncontrolled progression can in frequent cases lead to multiple organ failure, which is still associated with high mortality rates. Modern antibiotics made clear that the infection is only an initiating, and not always necessary, event of this syndrome as many patients with sepsis die despite effective eradication of the inciting pathogen. This observation critically contributed to a paradigm shift that focused the pathogenesis of sepsis on the host and not on the pathogen. However, therapeutic strategies based on the inhibition of proinflammatory critical mediators of sepsis or immunostimulation have so far failed to improve sepsis outcome and, therefore, this condition urgently needs transformative therapeutic ideas and strategies. Here we argue that the induction of tolerance, a defence strategy that minimises the impact of an infection on organ function without directly affecting the pathogen burden, is perhaps the missing but essential element to add to the current components of sepsis care and treatment. PMID- 26900876 TI - DFT Studies on the Mechanism of the Vanadium-Catalyzed Deoxydehydration of Diols. AB - The mechanism of the vanadium-catalyzed deoxydehydration of glycols to alkenes by phosphanes (Chapman, G.; Nicholas, K. M. Chem. Commun. 2013, 49, 8199-8201) has been investigated with density functional calculations. Two alternative pathways, A and B, have been evaluated, and the three stages generally recognized in DODH processes have been identified: (i) activation of the diol by condensation on the vanadium complex and eventual formation of vanadium-glycolate, (ii) oxygen atom transfer to phosphane with reduction to a vanadium(III) species, and, finally, (iii) alkene extrusion from the vanadium-glycolate with regeneration of the starting catalyst. Pathway B, in which the reduction by the phosphane from vanadium(V) to V(III) species occurred before the diol condensation, is energetically preferred to pathway A, in which the diol activation preceded the oxo-transfer to the phosphane reductant. PMID- 26900877 TI - Iridoid Glucosides and Diterpenoids from Caryopteris glutinosa. AB - Five new iridoid glucoside derivatives (1-5), three new diterpenoids (7, 12, and 15), and 11 known compounds were isolated from the aqueous EtOH extract of Caryopteris glutinosa. Cell-based estrogen biosynthesis assays indicated that caryopteriside C (3) and caryopterisoid B (12) promote the biosynthesis of estrogen E2, with EC50 values of 11.1 and 8.0 MUM, respectively, in human ovarian granulosa-like KGN cells via upregulating the expression of aromatase. PMID- 26900875 TI - Structure of the BAM complex and its implications for biogenesis of outer membrane proteins. AB - In Gram-negative bacteria, the assembly of beta-barrel outer-membrane proteins (OMPs) requires the beta-barrel-assembly machinery (BAM) complex. We determined the crystal structure of the 200-kDa BAM complex from Escherichia coli at 3.55-A resolution. The structure revealed that the BAM complex assembles into a hat-like shape, in which the BamA beta-barrel domain forms the hat's crown embedded in the outer membrane, and its five polypeptide transport-associated (POTRA) domains interact with the four lipoproteins BamB, BamC, BamD and BamE, thus forming the hat's brim in the periplasm. The assembly of the BAM complex creates a ring-like apparatus beneath the BamA beta-barrel in the periplasm and a potential substrate exit pore located at the outer membrane-periplasm interface. The complex structure suggests that the chaperone-bound OMP substrates may feed into the chamber of the ring-like apparatus and insert into the outer membrane via the potential substrate-exit pore in an energy-independent manner. PMID- 26900878 TI - The Sheffield ACS sickle knife for endoscopic anterior cricoid split. PMID- 26900879 TI - Shape Memory Composites Based on Electrospun Poly(vinyl alcohol) Fibers and a Thermoplastic Polyether Block Amide Elastomer. AB - The present study aimed at developing new thermally responsive shape-memory composites, that were fabricated by compacting mats of electrospun poly(vinyl alcohol) (PVA) fibers and sheets of a thermoplastic polyether block amide elastomer (PEBA). This design was based on the expectation that the combination of the rubber elasticity of the PEBA matrix and the mechanical switching exploitable through the reversible glass transition temperature (Tg) of the PVA filler could be combined to create materials that display shape memory characteristics as an emergent effect. Dynamic mechanical analyses (DMA) show that, upon introduction of 10-20% w/w PVA fibers, the room-temperature storage modulus (E') increased by a factor of 4-5 in comparison to the neat PEBA, and they reveal a stepwise reduction of E' around the Tg of PVA (85 degrees C). This transition could indeed be utilized to fix a temporary shape and recover the permanent shape. At low strain, the fixity was 66 +/- 14% and the recovery was 98 +/- 2%. Overall, the data validate a simple and practical strategy for the fabrication of shape memory composites that involves a melt compaction process and employs two commercially available polymers. PMID- 26900880 TI - Structural Analysis of the Tobramycin and Gentamicin Clinical Resistome Reveals Limitations for Next-generation Aminoglycoside Design. AB - Widespread use and misuse of antibiotics has allowed for the selection of resistant bacteria capable of avoiding the effects of antibiotics. The primary mechanism for resistance to aminoglycosides, a broad-spectrum class of antibiotics, is through covalent enzymatic modification of the drug, waning their bactericidal effect. Tobramycin and gentamicin are two medically important aminoglycosides targeted by several different resistance factors, including aminoglycoside 2"-nucleotidyltransferase [ANT(2")], the primary cause of aminoglycoside resistance in North America. We describe here two crystal structures of ANT(2"), each in complex with AMPCPP, Mn(2+), and either tobramycin or gentamicin. Together these structures outline ANT(2")'s specificity for clinically used substrates. Importantly, these structures complete our structural knowledge for the set of enzymes that most frequently confer clinically observed resistance to tobramycin and gentamicin. Comparison of tobramycin and gentamicin binding to enzymes in this resistome, as well as to the intended target, the bacterial ribosome, reveals surprising diversity in observed drug-target interactions. Analysis of the diverse binding modes informs that there are limited opportunities for developing aminoglycoside analogs capable of evading resistance. PMID- 26900881 TI - Bioelectrochemical Reduction of Fe(II)EDTA-NO in a Biofilm Electrode Reactor: Performance, Mechanism, and Kinetics. AB - A biofilm electrode reactor (BER) is proposed to effectively regenerate Fe(II)EDTA, a solvent for NOx removal from flue gas, from Fe(II)EDTA-NO, a spent solution. In this study, the performance, mechanism, and kinetics of the bioelectrochemical reduction of Fe(II)EDTA-NO were investigated. The pathways of Fe(II)EDTA-NO reduction were investigated via determination of nitrogen element balance in the BER and an abiotic electrode reactor. The experimental results indicate that the chelated NO (Fe(II)EDTA-NO) is reduced to N2 with N2O as an intermediate. However, the oxidation of NO occurred in the absence of Fe(II)EDTA in abiotic reactors. Furthermore, the accumulation of N2O was suppressed with the help of electricity. The preponderant electron donor for reduction of Fe(II)EDTA NO was also confirmed via analysis of the electron conservation. About 87% of Fe(II)EDTA-NO was reduced using Fe(II)EDTA as the electron donor in the presence of both glucose and cathode electrons while the cathode electrons were utilized for the reduction of Fe(III)EDTA to Fe(II)EDTA. Michaelis-Menten kinetic constants of bioelectrochemical reduction of Fe(II)EDTA-NO were also calculated. The maximum reduction rate of Fe(II)EDTA-NO was 13.04 mol m(-3) h(-1), which is 50% higher than that in a conventional biofilter. PMID- 26900882 TI - Synergism in a HDEHP/TOPO Liquid-Liquid Extraction System: An Intrinsic Ligands Property? AB - Among the proposed mechanisms to predict and understand synergism in solvent extraction, the possibility of a preorganization of the mixture of extractant molecules has never been considered. Whether involving synergistic aggregation as for solubilization enhancement with reverse micelles or favored molecular interaction between the extractant molecules, evaluation of this hypothesis requires characterization of the aggregates formed by the extractant molecules at different scales. We investigate here the HDEHP/TOPO couple of extractant with methods ranging from vibrational spectroscopy and ESI-MS spectrometry to vapor pressure osmometry and neutron and X-ray scattering to cover both molecular and supramolecular scales. These experimental methods are subjected to DFT calculations and molecular dynamics calculations, allowing a rationalization of the results through the different scales. Performed in the absence of any cation, this original study allows a decorrelation of the mechanisms at the origin of synergy: it appears that no clear preorganization of the extractants can explain the synergy and therefore that the synergistic aggregation observed in the presence of cations is rather due to the chelation mechanisms than to intrinsic properties of the extractant molecules. PMID- 26900883 TI - Perivascular epithelioid cell tumor of the ileum. A case report. AB - Perivascular epithelioid cell tumors (PEComa) are tumors of perivascular epithelioid cells with immunohistochemical features of smooth muscle and melanocytic tumors. The PEComa of the gastrointestinal tract is rare. The treatment is surgical, although there are data that suggest a good response to rapamycin. PMID- 26900884 TI - Phosphate and FGF23 in the renoprotective benefit of RAAS inhibition. AB - Renin angiotensin-aldosterone system (RAAS) blockade is a mainstay of chronic kidney disease (CKD) treatment given its beneficial effects on proteinuria, nephroprotection, heart disease and global mortality. The FGF23/Klotho/phosphate axis is crucial for phosphate excretion. During CKD, loss of Klotho, decreased phosphate excretion and FGF23 elevation are early events contributing both to renal disease progression and to cardiovascular complications. Experimental evidence suggests that Klotho replacement may improve renal and cardiovascular disease during CKD. Recent evidence suggests that both RAAS activation and proteinuria decrease Klotho expression and lead to phosphate retention and FGF23 elevation. In opposition RAAS blockade may reverse Klotho loss during CKD in both experimental and human studies, with direct and indirect expected beneficial effects on the kidney and cardiovascular system. This effect of RAAS blockade on the FGF23/Klotho/phosphate axis may participate in explaining some of the beneficial effects of these drugs during CKD. In this article we review the evidence linking RAAS blockade to modulation of the FGF23/Klotho/phosphate axis and the beneficial effects of these regulations. PMID- 26900885 TI - Influence of various sterilization procedures on TiO2 nanotubes used for biomedical devices. AB - Sterilization is the final surface treatment procedure of all implantable devices and is one of the key factors which have to be considered before implementation. Since different sterilization procedures for all implantable devices influence mechanical properties as well as biological response, the influence of different sterilization techniques on titanium nanotubes was studied. Commonly used sterilization techniques such as autoclaving, ultra-violet light sterilization, hydrogen peroxide plasma sterilization as well as the not so frequently used gaseous oxygen plasma sterilization were used. Three different nanotube diameters; 15 nm, 50 nm and 100 nm were employed to study the effects of various sterilization techniques. It was observed that autoclave sterilization resulted in destruction of nanotubular features on all three studied nanotube diameters, while UV-light and both kinds of plasma sterilization did not cause any significant morphological changes on the surfaces. Differences between the sterilization techniques employed influenced cytocompatibility, especially in the case of nanotubes with 100 nm diameter. PMID- 26900886 TI - Mortality in people with epilepsy: A statewide retrospective cohort study. AB - RATIONALE: People with epilepsy (PWE) have a higher risk of mortality than the general population, because of disparities in the receipt of appropriate epilepsy care, which may be affected by socioeconomic status, race/ethnicity and insurance coverage. Increased epilepsy prevalence has been associated with black race, low educational attainment, unemployment, and low income levels. Rural/urban residence may affect health through individual or environmental factors. Health disparities seen in rural residents are likely amplified in rural PWE because of limited access to specialized care. This analysis aims to examine the risk of mortality attributable to rural residence in the statewide population of South Carolina (SC) after adjusting for potential confounders. METHODS: This statewide retrospective cohort study of PWE seen in SC non-federal hospitals and emergency departments from 2000 to 2013 describes the hazard of mortality by rural/urban residential status in addition to other demographic and clinical characteristics. Differences in proportions were assessed by comparison of 95% confidence intervals. The association of rural/urban residence with mortality was further evaluated with Cox proportional hazard regression controlling for demographic and clinical covariables. RESULTS: 62,794 PWE were identified, of whom 21,451 (25.7%) had died. Deceased PWE were more likely to be rural residents, black, older than age 45, Medicare insured, in the middle income group, and have 5 or more comorbid conditions compared with living PWE. After adjustment for all other covariables, the risk of mortality did not differ by rural/urban residence. Blacks had a weak but significantly higher risk than whites (hazard ratio (HR)=1.14; 95% confidence interval (CI)=1.11, 1.18) while PWE of other races had a slightly lower risk of mortality (HR=0.79; 95% CI=0.67, 0.93). Male PWE had higher hazard as did Medicare, Medicaid or commercially insured PWE, those living in zip codes with annual median incomes less than $36,000, and those with 2 or more comorbid conditions. CONCLUSIONS: While other covariables were more strongly associated with mortality after adjustment (older age, insurance coverage, income level of zip code, and number of comorbidities), the finding of a higher hazard in black PWE than white PWE after adjustment for rural/urban residence and other demographic and clinical covariables is a concern. Further, the increased risk of mortality with higher numbers of comorbid conditions warrants regular management of these conditions. PMID- 26900887 TI - RNA helicase Belle/DDX3 regulates transgene expression in Drosophila. AB - Belle (Bel), the Drosophila homolog of the yeast DEAD-box RNA helicase DED1 and human DDX3, has been shown to be required for oogenesis and female fertility. Here we report a novel role of Bel in regulating the expression of transgenes. Abrogation of Bel by mutations or RNAi induces silencing of a variety of P element-derived transgenes. This silencing effect depends on downregulation of their RNA levels. Our genetic studies have revealed that the RNA helicase Spindle E (Spn-E), a nuage RNA helicase that plays a crucial role in regulating RNA processing and PIWI-interacting RNA (piRNA) biogenesis in germline cells, is required for loss-of-bel-induced transgene silencing. Conversely, Bel abrogation alleviates the nuage-protein mislocalization phenotype in spn-E mutants, suggesting a competitive relationship between these two RNA helicases. Additionally, disruption of the chromatin remodeling factor Mod(mdg4) or the microRNA biogenesis enzyme Dicer-1 (Dcr-1) also alleviates the transgene silencing phenotypes in bel mutants, suggesting the involvement of chromatin remodeling and microRNA biogenesis in loss-of-bel-induced transgene silencing. Finally we show that genetic inhibition of Bel function leads to de novo generation of piRNAs from the transgene region inserted in the genome, suggesting a potential piRNA-dependent mechanism that may mediate transgene silencing as Bel function is inhibited. PMID- 26900889 TI - The influences of perceived social support and personality on trajectories of subsequent depressive symptoms in Taiwanese youth. AB - Little is known about the combined effect of personality and social support on trajectories of depressive symptoms among youth. This study aims to investigate the influence of social support in different contexts on the development of depressive symptoms during adolescence and whether the association is moderated by adolescents' personality. The data using in this study is selected from the Taiwan Educational Panel Survey (TEPS), a longitudinal panel study since the year 2000 (at age 13) and three more waves (at ages 15, 17, and 18). A total of four waves of students' data (N = 4163) are analyzed using the latent growth models. The results indicate that the depressive symptom trajectory of Taiwan adolescents gradually grows in a quadratic curve. Social support in family context rather than school context was associated with depressive symptoms, while only a positive association is found between maternal support and depressive symptoms at the start. Meanwhile, increased extroversion personality is associated with the decreased initial level, increased linear changes, and decreased non-linear quadratic changes of adolescents' depressive symptoms. Further analyses show that a significant interaction between maternal support and extroversion personality is associated with increased non-linear quadratic growth curve of adolescents' depressive symptoms. In conclusion, adolescents' extroversion personality might moderate the effect of maternal support on developmental trajectory of depressive symptoms. Intervention that improves social support should take account for adolescent's personality, which may alter trajectory of psychological distress during adolescence. PMID- 26900888 TI - Interventions for comorbid problem gambling and psychiatric disorders: Advancing a developing field of research. AB - Despite significant psychiatric comorbidity in problem gambling, there is little evidence on which to base treatment recommendations for subpopulations of problem gamblers with comorbid psychiatric disorders. This mini-review draws on two separate systematic searches to identify possible interventions for comorbid problem gambling and psychiatric disorders, highlight the gaps in the currently available evidence base, and stimulate further research in this area. In this mini-review, only 21 studies that have conducted post-hoc analyses to explore the influence of psychiatric disorders or problem gambling subtypes on gambling outcomes from different types of treatment were identified. The findings of these studies suggest that most gambling treatments are not contraindicated by psychiatric disorders. Moreover, only 6 randomized studies comparing the efficacy of interventions targeted towards specific comorbidity subgroups with a control/comparison group were identified. The results of these studies provide preliminary evidence for modified dialectical behavior therapy for comorbid substance use, the addition of naltrexone to cognitive-behavioral therapy (CBT) for comorbid alcohol use problems, and the addition of N-acetylcysteine to tobacco support programs and imaginal desensitisation/motivational interviewing for comorbid nicotine dependence. They also suggest that lithium for comorbid bipolar disorder, escitalopram for comorbid anxiety disorders, and the addition of CBT to standard drug treatment for comorbid schizophrenia may be effective. Future research evaluating interventions sequenced according to disorder severity or the functional relationship between the gambling behavior and comorbid symptomatology, identifying psychiatric disorders as moderators of the efficacy of problem gambling interventions, and evaluating interventions matched to client comorbidity could advance this immature field of study. PMID- 26900890 TI - Association of neighborhood context with offspring risk of preterm birth and low birthweight: A systematic review and meta-analysis of population-based studies. AB - Findings from studies investigating associations of residential environment with poor birth outcomes have been inconsistent. In a systematic review and meta analysis, we examined associations of neighborhood disadvantage with preterm birth (PTB) and low birthweight (LBW), and explored differences in relationships among racial groups. Two reviewers searched English language articles in electronic databases of published literature. We used random effects logistic regression to calculate odds ratios (and 95% confidence intervals) relating neighborhood disadvantage with PTB and LBW. Neighborhood disadvantage, most disadvantaged versus least disadvantaged neighborhoods, was defined by researchers of included studies, and comprised of poverty, deprivation, racial residential segregation or racial composition, and crime. We identified 1314 citations in the systematic review. The meta-analyses included 7 PTB and 14 LBW cross-sectional studies conducted in the United States (U.S.). Overall, we found 27% [95%CI: 1.16, 1.39] and 11% [95%CI: 1.07, 1.14] higher risk for PTB and LBW among the most disadvantaged compared with least disadvantaged neighborhoods. No statistically significant association was found in meta-analyses of studies that adjusted for race. In race-stratified meta-analyses models, we found 48% [95%CI: 1.25, 1.75] and 61% [95%CI: 1.30, 2.00] higher odds of PTB and LBW among non Hispanic white mothers living in most disadvantaged neighborhoods compared with those living in least disadvantaged neighborhoods. Similar, but less strong, associations were observed for PTB (15% [95%CI: 1.09, 1.21]) and LBW (17% [95%CI: 1.10, 1.25]) among non-Hispanic black mothers. Neighborhood disadvantage is associated with PTB and LBW, however, associations may differ by race. Future studies evaluating causal mechanisms underlying the associations, and racial/ethnic differences in associations, are warranted. PMID- 26900892 TI - On-Water Synthesis of Biaryl Sulfonyl Fluorides. AB - Herein, we report an efficient, ligand-free, and additive-free Suzuki-Miyaura coupling that is compatible with the aromatic sulfonyl fluoride functional group. The protocol proceeds at room temperature, on water, and offers facile access to a wide range of biaryl sulfonyl fluorides as bioorthogonal "click" reagents. PMID- 26900891 TI - Mortality attributable to extreme temperatures in Spain: A comparative analysis by city. AB - BACKGROUND: The Low Temperature Days (LTD) have attracted far less attention than that of High Temperature Days (HTD), though its impact on mortality is at least comparable. This lower degree of attention may perhaps be due to the fact that its influence on mortality is less pronounced and longer-term, and that there are other concomitant infectious winters factors. In a climate-change scenario, the studies undertaken to date report differing results. The aim of this study was to analyse mortality attributable to both thermal extremes in Spain's 52 provinces across the period 2000-2009, and estimate the related economic cost to show the benefit or "profitability" of implementing prevention plans against LTD. METHODS: Previous studies enabled us: to obtain the maximum daily temperature above which HTD occurred and the minimum daily temperature below which LTD occurred in the 52 provincial capitals analysed across the same study period; and to calculate the relative and attributable risks (%) associated with daily mortality in each capital. These measures of association were then used to make different calculations to obtain the daily mean mortality attributable to both thermal extremes. To this end, we obtained a summary of the number of degrees whereby the temperature exceeded (excess degrees C) or fell short (deficit degrees C) of the threshold temperature for each capital, and calculated the respective number of extreme temperatures days. The economic estimates rated the prevention plans as being 68% effective. RESULTS: Over the period considered, the number of HTD (4373) was higher than the number of LTD (3006) for Spain as a whole. Notwithstanding this, in every provincial capital the mean daily mortality attributable to heat was lower (3deaths/day) than that attributable to cold (3.48deaths/day). In terms of the economic impact of the activation of prevention plans against LTD, these could be assumed to avoid 2.37 deaths on each LTD, which translated as a saving of ?0.29M. Similarly, in the case of heat, 2.04 deaths could be assumed to be avoided each day on which the prevention plan against HTD was activated, amounting to a saving of ?0.25M. While the economic cost of cold related mortality across the ten-year period 2000-2009 was ?871.7M, that attributable to heat could be put at ?1093.2M. CONCLUSION: The effect of extreme temperatures on daily mortality was similar across the study period for Spain overall. The lower number of days with LTD meant, however, that daily cold related mortality was higher than daily heat-related mortality, thereby making prevention plans against LTD more "profitable" prevention plans against HTD in terms of avoidable mortality. PMID- 26900893 TI - Does action follow intention with participation in home and group-based falls prevention exercise programs? An exploratory, prospective, observational study. AB - BACKGROUND: Exercise for falls prevention is effective but of limited uptake in real life. The link between intention and behavior is central to many health behavior models, but has not been examined in the falls prevention exercise context. OBJECTIVE: This study examines this relationship and prospectively identifies factors associated with participation in group and home-based falls prevention exercise. DESIGN: This was an observational study of community dwelling adults in Australia >70 years of age with a 12 month follow-up (n=394 commenced baseline assessment, n=247 commenced follow-up). METHODS: Intention, and other potential predictive factors examined, were measured at baseline while participation was measured using self-report at 12 month follow-up. RESULTS: Between 65% and 72% of our sample at baseline agreed or strongly agreed they would participate in the falls prevention exercise programs. n=27 respondents participated in home-based exercise during follow-up and had intention to do so while n=29 who participated did not have intention. In contrast, n=43 respondents participated in group exercise and had intention to do so compared to 11 who participated but did not intend to at baseline. Perception of personal effectiveness and previous exposure to the exercise intervention were most strongly predictive of future participation. CONCLUSION: More people who do not want to participate in home exercise actually participate in home exercise than people who do not want to participate in group exercise that actually do. It may be easier to convince people who do not want to participate in falls prevention exercise to participate in a home program. PMID- 26900895 TI - Long-term outcomes of brief, intensive CBT for specific phobias: The negative impact of ADHD symptoms. AB - OBJECTIVES: The objectives were twofold: (a) examine long-term treatment effects in youth receiving 1-session treatment (OST) or educational support (EST) for a specific phobia (SP) and (b) examine the differential predictive and moderation effects of attention-deficit/hyperactivity disorder (ADHD) symptoms on immediate and long-term outcomes following the interventions. METHOD: Eighty-three children (ages 6-15, 47% female, 89% White) with a SP were randomly assigned to receive OST or EST. Follow up assessments occurred at 1 week, 6 months, 1 year, and 4 years. Hierarchical linear growth modeling (HLGM) was used to explore the association of parent-reported ADHD symptoms, the 2 treatment conditions (i.e., OST vs. EST), and the trajectory of change in the severity of the SP from pretreatment to the 4-year follow-up. Age, conduct problems and learning problems were controlled for in all analyses. RESULTS: A greater immediate reduction in severity rating of the SP was observed in the OST compared to EST, whereas the trajectory of long-term outcomes was similar across conditions over time. Higher levels of ADHD symptoms predicted poor immediate and long-term treatment outcomes across treatment conditions. ADHD symptoms, however, did not moderate the relationship between treatment condition and immediate or long-term treatment outcomes. CONCLUSIONS: The results of the study need to be interpreted in light of several study limitations. However, if confirmed, the findings suggest that anxious youth with comorbid ADHD symptoms are less likely to benefit from brief, intensive psychotherapy and may require either longer, standard CBT treatment or adjunctive pharmacotherapy. PMID- 26900896 TI - The Impact of Chocolate Goat's and Cow's Milk on Postresistance Exercise Endocrine Responses and Isometric Mid-Thigh Pull Performance. AB - The present investigation examined the effects of chocolate cow's and goat's milk on endocrine responses and isometric mid-thigh pull performance post back squat exercise. Twelve college-aged males volunteered to participate and reported to the lab on four occasions. The first visit included anthropometric measurement, one-repetition back squat (1RM), and familiarization with the isometric mid-thigh pull assessment (IMTP). During the subsequent three visits, five sets of eight repetitions of the back squat exercise at 80% of 1RM were performed. For these trials, the participants performed an IMTP and gave a saliva sample prior to, immediately after, 1 hr and 2 hr post exercise. After exercise, a treatment of low-fat chocolate goat's milk (355 ml, 225 kcal), low-fat chocolate cow's milk (355 ml, 225 kcal), or control (water 355 ml, 0 kcal) was given in a counterbalanced order. Saliva samples were analyzed for testosterone, cortisol, and dehydroepiandrosterone (DHEA). Cortisol and DHEA hormone were unaffected by exercise; however, testosterone values did increase significantly post exercise. For IMTP, there was a significant main effect for time (F = 8.41, p = .007) but no treatment or interactions effects. N changes were noted post supplementation for cortisol or DHEA, but testosterone was found to be significantly reduced in both diary treatments compared to control (F = 4.27, p = .022). Based upon these data, it appears that a single treatment of chocolate goat's or cow's milk results in similar endocrine alterations but both fail to enhance postexercise isometric strength following resistance exercise. PMID- 26900894 TI - Changes in temporal attention inhibition following prolonged exposure and sertraline in the treatment of PTSD. AB - OBJECTIVE: Attentional inhibitory deficits expressed as difficulty ignoring irrelevant stimuli in the pursuit of goal-directed behavior may serve as a fundamental mechanism of posttraumatic stress disorder (PTSD). Evidence of inhibitory processes as central to extinction suggests that exposure-based treatments may act more directly on the inhibitory deficits implicated in PTSD, whereas, in facilitating serotonergic neurotransmission, selective serotonin reuptake inhibitors (SSRIs) may be less direct and bring about general neurochemical changes in the fear circuitry. If these inhibitory deficits underlie PTSD, then inhibition should improve with successful treatment, with those treated with prolonged exposure (PE) potentially resulting in greater changes in inhibition than those treated with sertraline. METHOD: Changes in temporal attentional inhibition, using an attentional blink (AB) paradigm, were examined at pre- and posttreatment in 49 individuals (74.5% female, 66.7% Caucasian, age M = 37.69, SD = 12.8 years) with chronic PTSD. Participants completed 10 weeks of either PE or sertraline. RESULTS: Individuals who made greater improvements with PE showed faster improvements in temporal inhibition on the critical inhibitory lag of AB than those who made greater improvements with sertraline (d = 0.94). These changes could not be accounted for by basic attention. CONCLUSIONS: Greater improvement in fundamental attentional inhibitory processes with better treatment response to PE, compared with sertraline, suggests potential specificity in how PTSD treatments normalize inhibitory processes, such that exposure-based treatments like PE may target inhibitory processes and improve basic inhibitory functioning. PMID- 26900897 TI - What Keeps Passion Alive? Sexual Satisfaction Is Associated With Sexual Communication, Mood Setting, Sexual Variety, Oral Sex, Orgasm, and Sex Frequency in a National U.S. Study. AB - Passion and sexual satisfaction typically diminish in longer-term relationships, but this decline is not inevitable. We identified the attitudes and behaviors that most strongly differentiated sexually satisfied from dissatisfied men and women who had been together for at least three years (N = 38,747). Data were collected in 2006 from cohabiting and married men (M) and women (W) via an online survey on a major national U.S. news Web site. The vast majority of these participants reported being satisfied with their sex lives during their first six months together (83% W; 83% M). Satisfaction with their current sex lives was more variable, with approximately half of participants reporting overall satisfaction (55% W; 43% M) and the rest feeling neutral (18% W; 16% M) or dissatisfied (27% W; 41% M). More than one in three respondents (38% W; 32% M) claimed their sex lives were as passionate now as in the beginning. Sexual satisfaction and maintenance of passion were higher among people who had sex most frequently, received more oral sex, had more consistent orgasms, and incorporated more variety of sexual acts, mood setting, and sexual communication. We discuss implications of these findings for research and for helping people revitalize their sex lives. PMID- 26900898 TI - Comment on "The Performance and Usability of a Factory-Calibrated Flash Glucose Monitoring System" by Bailey et al. PMID- 26900904 TI - Assessment of Prostate Cancer Aggressiveness by Use of the Combination of Quantitative DWI and Dynamic Contrast-Enhanced MRI. AB - OBJECTIVE: The objective of this study was to investigate whether the apparent diffusion coefficient (ADC) value from DWI and the forward volume transfer constant (K(trans)) value from dynamic contrast-enhanced MRI independently predict prostate cancer aggressiveness, and to determine whether the combination of both parameters performs better than either parameter alone in assessing tumor aggressiveness before treatment. MATERIALS AND METHODS: This retrospective study included 158 men with histopathologically confirmed prostate cancer who underwent 3-T MRI before undergoing prostatectomy in 2011. Whole-mount step-section pathologic maps identified 195 prostate cancer foci that were 0.5 mL or larger; these foci were then volumetrically assessed to calculate the per-tumor ADC and K(trans) values. Associations between MRI and histopathologic parameters were assessed using Spearman correlation coefficients, univariate and multivariable logistic regression, and AUCs. RESULTS: The median ADC and K(trans) values showed moderate correlation only for tumors for which the Gleason score (GS) was 4 + 4 or higher (rho = 0.547; p = 0.042). The tumor ADC value was statistically significantly associated with all dichotomized GSs (p < 0.005), including a GS of 3 + 3 versus a GS of 3 + 4 or higher (AUC, 0.693; p = 0.001). The tumor K(trans) value differed statistically significantly only between tumors with a GS of 3 + 3 and those with a primary Gleason grade of 4 (p <= 0.015), and it made a statistically significant contribution only in differentiating tumors with a GS of 4 + 3 or higher (AUC, 0.711; p < 0.001) and those with a GS of 4 + 4 or higher (AUC, 0.788; p < 0.001) from lower-grade tumors. Combining ADC and K(trans) values improved diagnostic performance in characterizing tumors with a GS of 4 + 3 or higher and those with a GS of 4 + 4 or higher (AUC, 0.739 and 0.856, respectively; p < 0.01). CONCLUSION: Although the ADC value helped to differentiate between all GSs, the K(trans) value was only a benefit in characterizing more aggressive tumors. Combining these parameters improves their performance in identifying patients with aggressive tumors who may require radical treatment. PMID- 26900905 TI - Does Reducing the Concentration of Bupivacaine When Performing Therapeutic Shoulder Joint Injections Impact the Clinical Outcome? AB - OBJECTIVE: Mixtures of local anesthetics and steroids are routinely injected intraarticularly to temporarily relieve joint pain, even though local anesthetics have been reported to cause chondrocyte death in a dose- and time-dependent manner. This study aimed to determine if intraarticular injections of bupivacaine 0.5% and bupivacaine 0.25% would provide similar pain relief. MATERIALS AND METHODS: All fluoroscopically guided glenohumeral joint injections performed using 2.5 mL of bupivacaine and 0.5 mL (20 mg) of triamcinolone acetonide over a 42-month period were included if a pain score was recorded before, 5-10 minutes after, and 1 week after injection. Pain reduction of more than 2 points was considered much improved clinically with pain reduction of more than 1 point considered the minimum clinically important difference (MCID) threshold. RESULTS: Statistically significant and much improved pain reduction was achieved using both bupivacaine 0.5% and 0.25% 5-10 minutes (-3.7 points; 95% CI, -3.4 to -4.0 points; p <= 0.001; and -3.3 points; 95% CI, -3.0 to -3.5 points; p <= 0.001) and 1 week (-2.5 points; 95% CI, -2.2 to -2.9 points; p <= 0.001; and -2.1 points; 95% CI, -1.8 to -2.3 points; p <= 0.001) after injection, respectively. Adjusting for age, sex, pain score before injection, and indication, the mean decrease in pain was greater in the bupivacaine 0.5% group by 0.30 points 5-10 minutes after injection (95% CI, -0.03 to 0.63 points; p = 0.08) and 0.46 points 1 week after injection (95% CI, 0.13-0.77 points; p = 0.01). CONCLUSION: Both bupivacaine 0.5% and bupivacaine 0.25% provide statistically significant and much improved pain relief 5-10 minutes and 1 week after intraarticular glenohumeral injections. Bupivacaine 0.5% provided greater pain relief than bupivacaine 0.25%, but the difference was less than 0.5 points and therefore did not meet the MCID threshold. PMID- 26900903 TI - Mercapturic acids: recent advances in their determination by liquid chromatography/mass spectrometry and their use in toxicant metabolism studies and in occupational and environmental exposure studies. AB - This review describes recent selected HPLC/MS methods for the determination of urinary mercapturates that are useful as noninvasive biomarkers in characterizing human exposure to electrophilic industrial chemicals in occupational and environmental studies. High-performance liquid chromatography/mass spectrometry is a sensitive and specific method for analysis of small molecules found in biological fluids. In this review, recent selected mercapturate quantification methods are summarized and specific cases are presented. The biological formation of mercapturates is introduced and their use as indicators of metabolic processing of reactive toxicants is discussed, as well as future trends and limitations in this area of research. PMID- 26900906 TI - Triggering Akkermansia with dietary polyphenols: A new weapon to combat the metabolic syndrome? AB - The gut and its bacterial colonizers are now well characterized as key players in whole-body metabolism, opening new avenues of research and generating great expectation for new treatments against obesity and its cardiometabolic complications. As diet is the main environmental factor affecting the gut microbiota, it has been suggested that fruits and vegetables, whose consumption is strongly associated with a healthy lifestyle, may carry phytochemicals that could help maintain intestinal homeostasis and metabolic health. We recently demonstrated that oral administration of a cranberry extract rich in polyphenols prevented diet-induced obesity and several detrimental features of the metabolic syndrome in association with a remarkable increase in the abundance of the mucin degrading bacterium Akkermansia in the gut microbiota of mice. This addendum provides an extended discussion in light of recent discoveries suggesting a mechanistic link between polyphenols and Akkermansia, also contemplating how this unique microorganism may be exploited to fight the metabolic syndrome. PMID- 26900907 TI - Influence of pro-algesic foods on chronic pain conditions. AB - This paper examines current knowledge about putative "pro-algesic" dietary components, and discusses whether limiting the intake of these substances can help improve chronic pain. Although there is a common impression that numerous food components, natural and synthetic, can cause or worsen pain symptoms, very few of these substances have been investigated. This article focuses on four substances, monosodium glutamate, aspartame, arachidonic acid, and caffeine, where research shows that overconsumption may induce or worsen pain. For each substance, the mechanism whereby it may act to induce pain is examined, and any clinical trials examining the effectiveness of reducing the intake of the substance discussed. While all four substances are associated with pain, decreased consumption of them does not consistently reduce pain. PMID- 26900908 TI - Revision of infected knee arthroplasties in Denmark. AB - Background and purpose - The surgical treatment of periprosthetic knee infection is generally either a partial revision procedure (open debridement and exchange of the tibial insert) or a 2-stage exchange arthroplasty procedure. We describe the failure rates of these procedures on a nationwide basis. Patients and methods - 105 partial revisions (100 patients) and 215 potential 2-stage revision procedures (205 patients) performed due to infection from July 1, 2011 to June 30, 2013 were identified from the Danish Knee Arthroplasty Register (DKR). Failure was defined as surgically related death <= 90 days postoperatively, re revision due to infection, or not reaching the second stage for a planned 2-stage procedure within a median follow-up period of 3.2 (2.2-4.2) years. Results - The failure rate of the partial revisions was 43%. 71 of the partial revisions (67%) were revisions of a primary prosthesis with a re-revision rate due to infection of 34%, as compared to 55% in revisions of a revision prosthesis (p = 0.05). The failure rate of the 2-stage revisions was 30%. Median time interval between stages was 84 (9-597) days. 117 (54%) of the 2-stage revisions were revisions of a primary prosthesis with a re-revision rate due to infection of 21%, as compared to 29% in revisions of a previously revised prosthesis (p = 0.1). Overall postoperative mortality was 0.6% in high-volume centers (> 30 procedures within 2 years) as opposed to 7% in the remaining centers (p = 0.003). Interpretation - The failure rates of 43% after the partial revision procedures and 30% after the 2-stage revisions in combination with the higher mortality outside high-volume centers call for centralization and reconsideration of surgical strategies. PMID- 26900909 TI - New theory of uterovaginal embryogenesis. AB - BACKGROUND: The explanation of uterine and vaginal embryogenesis in humans still poses many controversies, because it is difficult to assess early stages of an embryo. The literature review revealed many disagreements in Mullerian theory, inciting some authors to propose new embryological hypotheses. In the original Mullerian theory: the paramesonephral ducts form the Fallopian tubes, uterus and vagina; the mesonephral ducts regress in female embryos. AIMS: The aim of this article is to investigate the development of Mullerian ducts in humans, using comparative analysis of fundamental embryological theory and various utero vaginal anomalies. MATERIAL AND METHODS: Between 1998 and 2015, 434 patients with various uterovaginal malformations had been operated on at the Scientific Centre of Obstetrics Gynaecology and Perynatology in Moscow. The anatomies of the uterovaginal malformations in these patients were diagnosed with ultrasound and MRI and then verified during surgical correction by laparoscopy. RESULTS: A systematic comparison of uterovaginal malformations to those in the literature has allowed us to formulate a new theory of embryonic morphogenesis. The new theory is significantly different: ovary, ovarian ligamentum proprium, and ligamentum teres uteri derive from gonadal ridges; Fallopian tubes and vagina completely develop from mesonephral ducts. The uterus develops in the area of intersection between the mesonephral ducts with gonadal ridges by the fusion of the two. CONCLUSIONS: The new theory may to induce future embryological studies. The hypothetic possibility that the ovary and endometrium derive from the gonadal ridges could be the key to understanding the enigmatic aetiologies of extragenital and ovarian endometriosis. PMID- 26900910 TI - Methods and background characteristics of the TOHNN study: a population-based study of oral health conditions in northern Norway. AB - OBJECTIVES: The aim of the Tromstannen-Oral Health in Northern Norway (TOHNN) study was to investigate oral health and dental-related diseases in an adult population. This article provides an overview of the background of the study and a description of the sample characteristics and methods employed in data collection. STUDY DESIGN: Cross-sectional population-based study including a questionnaire and clinical dental examination. METHODS: A randomly selected sample of 2,909 individuals (20-79 years old) drawn from the population register was invited to participate in the study. The data were collected between October 2013 and November 2014 in Troms County in northern Norway. The questionnaire focused on oral health-related behaviours and attitudes, oral health-related quality of life, sense of coherence, dental anxiety and symptoms from the temporomandibular joint. The dental examinations, including radiographs, were conducted by 11 dental teams in 5 dental offices. The examination comprised of registration of dental caries, full mouth periodontal status, temporomandibular disorders, mucosal lesions and height and weight. The participants were grouped by age (20-34, 35-49, 50-64 and 65-79) and ethnicity (Norwegian, Sami, other European and other world). RESULTS: From the original sample of 2,909 individuals, 1,986 (68.3%) people participated, of whom 1,019 (51.3%) were women. The highest attendance rate was among women 20-34 years old (80.3%) and the lowest in the oldest age group of women (55.4%). There was no difference in response rate between rural and urban areas. There was a positive correlation between population size and household gross income (p < 0.001) and education level (p < 0.001). The majority of Sami resided in smaller municipalities. In larger cities, most participants used private dental health care services, whereas, in rural areas, most participants used the public dental health care service. CONCLUSION: The TOHNN study has the potential to generate new knowledge on a wide range of oral health conditions beneficial to the population in Troms County. Due to the high participation rate, generalization both nationally and to the circumpolar area ought to be possible. PMID- 26900911 TI - The use of ultrasound and other markers for early detection of preeclampsia. AB - Preeclampsia (PE) is a multisystem disorder of pregnancy classically characterized with the onset of hypertension after 20 weeks gestation in the presence of proteinuria. PE typically affects 2-8% of pregnancies and is a leading cause of maternal and perinatal morbidity and mortality. This article reviews the most effective biomarkers used in first trimester screening for PE. It explores their use both in isolation and as part of an algorithm to yield the best detection rates. Screening by a combination of maternal risk factors, uterine artery Doppler, mean arterial pressure, maternal serum PAPP-A and PlGF can identify about 75% of cases of preterm PE for a false-positive rate of 10%. By identifying these patients at high risk for PE, appropriately tailored antenatal surveillance can be instigated and prophylactic pharmacological interventions can be prescribed to improve placentation and ultimately, the outcome for both the mother and fetus. PMID- 26900912 TI - Impact of a Surgeon-Led Peripherally Inserted Central Venous Catheter Team on Peripherally Inserted Central Venous Catheter-Related Complications and Costs. AB - BACKGROUND: Peripherally inserted central venous catheters (PICCs) are popular for a broad range of indications. As with other forms of central access, PICC use can be associated with serious and potentially costly complications. In 2000, in response to the rising popularity of PICC use, a surgeon-led team was created to steward their placement. All requests were screened rigorously to ensure rational use. Our hypothesis was that creation of a dedicated PICC team would decrease inappropriate PICC placement, overall complication rates, and cost. METHODS: The study was a retrospective review of prospectively collected data captured in the PICC team-maintained database between 2000 and 2013. The database was reviewed for PICC indications, reasons PICC requests were denied, and septic or thrombotic complications after PICC placement. To estimate cost savings, PICC supplies and each occurrence of blood stream infection (BSI) and thrombotic complication was assigned a cost on the basis of the available literature. RESULTS: Between 2000 and 2013, 35,651 PICC placements were requested, of which 24,638 (69.1%) were approved, 22,157 (62.1%) immediately and 2,481 (6.9%) after initial refusal in view of further review of the indications. Most (95%) of the PICCs inserted were placed at the bedside within 1 d of approval. Blood stream infections occurred in 5.9% of patients and thrombosis in 2.7%. The attributable costs saved by declining placement of unnecessary PICCs, assuming the same proportions of patients would have developed a complication, could be as high as $5.4 million (M) in supplies, $7.77 M in avoided BSI and $2.25 M in avoided thrombotic complications, for a total savings of $15.44 M. CONCLUSIONS: The implementation of a surgeon-led PICC team had a significant impact on the placement rate, reducing cost by supplies foregone and complications avoided. Cost savings related to PICC placement alone should be considered as the definite cost savings because of the judicious allocation of resources. PMID- 26900913 TI - C3-Luc Cells Are an Excellent Model for Evaluation of Cellular Immunity following HPV16L1 Vaccination. AB - C3 and TC-1 are the two model cell lines most commonly used in studies of vaccines and drugs against human papillomavirus (HPV) infection. Because C3 cells contain both the HPV16 E and L genes, but TC-1 cells contain only the HPV16 E genes, C3 cells are usually used as the model cell line in studies targeting the HPV16 L protein. However, expression of the L1 protein is difficult to detect in C3 cells using common methods. In our study, Short tandem repeat analysis (STR) was used to demonstrate that C3 cells are indeed derived from mice, PCR results show that HPV16 L1, E6 and E7 genes were detected in C3 genomic DNA, and RT-PCR results demonstrated that L1 transcription had occurred in C3 cells. However, the expression of C3 protein was not found in the results of western blot and immunohistochemistry (IHC). Growth and proliferation of C3 were inhibited by mice spleen lymphocytes that had been immunized with a vaccine against HPV16L1. The luciferase gene was integrated into C3 cells, and it was confirmed that addition of the exogenous gene had no effect on C3 cells by comparing cell growth and tumor formation with untransformed cells. Cells stably expressing luciferase (C3 luc) were screened and subcutaneously injected into the mice. Tumors became established and were observed using a Spectrum Pre-clinical in Vivo Imaging System. Tumor size of mice in the different groups at various time points was calculated by counting photons. The sensitivity of the animals to the vaccine was quantified by statistical comparison. Ten or 30 days following injection of the C3-luc cells, tumor size differed significantly between the PBS and vaccine groups, indicating that C3 cells were susceptible to vaccination even after tumors were formed in vivo. PMID- 26900914 TI - Short Meditation Trainings Enhance Non-REM Sleep Low-Frequency Oscillations. AB - STUDY OBJECTIVES: We have recently shown higher parietal-occipital EEG gamma activity during sleep in long-term meditators compared to meditation-naive individuals. This gamma increase was specific for NREM sleep, was present throughout the entire night and correlated with meditation expertise, thus suggesting underlying long-lasting neuroplastic changes induced through prolonged training. The aim of this study was to explore the neuroplastic changes acutely induced by 2 intensive days of different meditation practices in the same group of practitioners. We also repeated baseline recordings in a meditation-naive cohort to account for time effects on sleep EEG activity. DESIGN: High-density EEG recordings of human brain activity were acquired over the course of whole sleep nights following intervention. SETTING: Sound-attenuated sleep research room. PATIENTS OR PARTICIPANTS: Twenty-four long-term meditators and twenty-four meditation-naive controls. INTERVENTIONS: Two 8-h sessions of either a mindfulness-based meditation or a form of meditation designed to cultivate compassion and loving kindness, hereafter referred to as compassion meditation. MEASUREMENTS AND RESULTS: We found an increase in EEG low-frequency oscillatory activities (1-12 Hz, centered around 7-8 Hz) over prefrontal and left parietal electrodes across whole night NREM cycles. This power increase peaked early in the night and extended during the third cycle to high-frequencies up to the gamma range (25-40 Hz). There was no difference in sleep EEG activity between meditation styles in long-term meditators nor in the meditation naive group across different time points. Furthermore, the prefrontal-parietal changes were dependent on meditation life experience. CONCLUSIONS: This low-frequency prefrontal-parietal activation likely reflects acute, meditation-related plastic changes occurring during wakefulness, and may underlie a top-down regulation from frontal and anterior parietal areas to the posterior parietal and occipital regions showing chronic, long-lasting plastic changes in long-term meditators. PMID- 26900915 TI - Pre-Dialysis Visits to a Nephrology Department and Major Cardiovascular Events in Patients Undergoing Dialysis. AB - BACKGROUND AND OBJECTIVES: Pre-dialysis care by a nephrology out-patient department (OPD) may affect the outcomes of patients who ultimately undergo maintenance dialysis. This study examined the effect of pre-dialysis care by a nephrology OPD on the incidence of one-year major cardiovascular events after initiation of dialysis. DESIGN, SETTING PARTICIPANTS, & MEASUREMENTS: The study consisted of Taiwanese patients with chronic kidney disease (CKD) who commenced dialysis from 2006 to 2008. The number of nephrology OPD visits during the critical care period (within 6 months of initiation of dialysis) and the early care period (6-36 months before initiation of dialysis) were analyzed. The primary outcome measure was one-year major cardiovascular events. RESULTS: A total of 1191 CKD patients who initiated dialysis from 2006 to 2008 were included. Binary logistic regression showed that patients with ?3 visits during the critical care period and those with ?11 visits during the early care period had fewer composite major cardiovascular events than those with 0 visits. Patients with early referral are less likely to experience composite major cardiovascular events than those with late referral, with aOR 0.574 (95% CI = 0.43-0.77, P<0.001). Patients with both ?3 visits during critical care period and ?11 visits during early care period were less likely to experience composite major cardiovascular events (aOR = 0.25, 95% CI = 0.16-0.39, P < 0.001). CONCLUSIONS: Patients with adequate pre-dialysis nephrology OPD visits, not just early referral, may had fewer one-year composite major cardiovascular events after initiation of dialysis. This information may be important to medical care providers and public health policy makers in their efforts to improve the well being of CKD patients. PMID- 26900916 TI - Hydrology Affects Environmental and Spatial Structuring of Microalgal Metacommunities in Tropical Pacific Coast Wetlands. AB - The alternating climate between wet and dry periods has important effects on the hydrology and therefore on niche-based processes of water bodies in tropical areas. Additionally, assemblages of microorganism can show spatial patterns, in the form of a distance decay relationship due to their size or life form. We aimed to test spatial and environmental effects, modulated by a seasonal flooding climatic pattern, on the distribution of microalgae in 30 wetlands of a tropical dry forest region: the Pacific coast of Costa Rica and Nicaragua. Three surveys were conducted corresponding to the beginning, the highest peak, and the end of the hydrological year during the wet season, and species abundance and composition of planktonic and benthic microalgae was determined. Variation partitioning analysis (as explained by spatial distance or environmental factors) was applied to each seasonal dataset by means of partial redundancy analysis. Our results show that microalgal assemblages were structured by spatial and environmental factors depending on the hydrological period of the year. At the onset of hydroperiod and during flooding, neutral effects dominated community dynamics, but niche-based local effects resulted in more structured algal communities at the final periods of desiccating water bodies. Results suggest that climate-mediated effects on hydrology can influence the relative role of spatial and environmental factors on metacommunities of microalgae. Such variability needs to be accounted in order to describe accurately community dynamics in tropical coastal wetlands. PMID- 26900918 TI - Human genome regulation. PMID- 26900917 TI - First Fall-Related Injuries Requiring Hospitalization Increase the Risk of Recurrent Injurious Falls: A Nationwide Cohort Study in Taiwan. AB - OBJECTIVES: Recurrent falls not only have risk factors different from those of single falls but also have less favorable outcomes. The aim of our study was to determine the association between the injury characteristics of a first fall and the likelihood of recurrent injurious falls in a cohort of hospitalized patients. METHODS: We designed a nationwide retrospective cohort study and selected hospitalized patients who had injurious falls between 2001 and 2010. Cox proportional hazards models were used to estimate the hazard ratios (HRs) of recurrent injurious falls requiring hospitalization in the following year on the basis of the patients' demographic characteristics, comorbidities, and the characteristics of injuries from the first injurious fall requiring hospitalization. RESULTS: Among the 504 512 patients hospitalized for injurious falls, 19 442 experienced recurrent injurious falls requiring hospitalization. The 1-year incidence of recurrent injurious falls requiring hospitalization was 3.85%. The incidence density was the highest within the 3-month period after the first injurious fall. The risk of recurrent injurious falls among patients aged 40 to 64, 65 to 74, and >= 75 years increased progressively (HR: 2.11, 95% confidence interval [CI]: 1.90-2.34; HR: 2.80, 95% CI: 2.51-3.11; and HR: 3.80, 95% CI: 3.42-4.23, respectively). The length of hospitalization (LOH) >= 15 or >= 31 days (HR: 1.39, 95% CI: 1.30-1.48; and HR: 1.59, 95% CI: 1.43-1.77, respectively) and injury to the head (HR: 1.59, 95% CI: 1.53-1.65) or spine (HR: 1.66, 95% CI: 1.59-1.74) were also found to be major risk factors. CONCLUSIONS: Our findings show that the LOH and head and spine injuries are associated with an increased risk of recurrent injurious falls leading to hospitalization. The risk of recurrent injurious falls requiring hospitalization increased significantly among adults older than 40 years. We suggest further research on the effects of injury characteristics associated with the first injurious fall requiring hospitalization and resultant anatomical damages on the risk of recurrent injurious falls requiring hospitalization. High-risk patients should receive tailored rehabilitation addressing their respective injuries within 3 months after hospital discharge. PMID- 26900920 TI - Biomimetic Hierarchical Assembly of Helical Supraparticles from Chiral Nanoparticles. AB - Chiroptical materials found in butterflies, beetles, stomatopod crustaceans, and other creatures are attributed to biocomposites with helical motifs and multiscale hierarchical organization. These structurally sophisticated materials self-assemble from primitive nanoscale building blocks, a process that is simpler and more energy efficient than many top-down methods currently used to produce similarly sized three-dimensional materials. Here, we report that molecular-scale chirality of a CdTe nanoparticle surface can be translated to nanoscale helical assemblies, leading to chiroptical activity in the visible electromagnetic range. Chiral CdTe nanoparticles coated with cysteine self-organize around Te cores to produce helical supraparticles. D-/L-Form of the amino acid determines the dominant left/right helicity of the supraparticles. Coarse-grained molecular dynamics simulations with a helical pair-potential confirm the assembly mechanism and the origin of its enantioselectivity, providing a framework for engineering three-dimensional chiral materials by self-assembly. The helical supraparticles further self-organize into lamellar crystals with liquid crystalline order, demonstrating the possibility of hierarchical organization and with multiple structural motifs and length scales determined by molecular-scale asymmetry of nanoparticle interactions. PMID- 26900919 TI - ER Adaptor SCAP Translocates and Recruits IRF3 to Perinuclear Microsome Induced by Cytosolic Microbial DNAs. AB - Stimulator of interferon genes (STING, also known as MITA, ERIS or MPYS) induces the activation of TBK1 kinase and IRF3 transcription factor, upon sensing of microbial DNAs. How IRF3 is recruited onto the STING signalosome remains unknown. We report here that silencing of the ER adaptor SCAP markedly impairs the IRF3 responsive gene expression induced by STING. Scap knockdown mice are more susceptible to HSV-1 infection. Interestingly, SCAP translocates from ER, via Golgi, to perinuclear microsome in a STING-dependent manner. Mechanistically, the N-terminal transmembrane domain of SCAP interacts with STING, and the C-terminal cytosolic domain of SCAP binds to IRF3, thus recruiting IRF3 onto STING signalosome. Mis-localization of SCAP abolishes its antiviral function. Collectively, this study characterizes SCAP as an essential adaptor in the STING signaling pathway, uncovering a critical missing link in DNAs-triggered host antiviral responses. PMID- 26900921 TI - Childhood skin and soft tissue infections: new discoveries and guidelines regarding the management of bacterial soft tissue infections, molluscum contagiosum, and warts. AB - PURPOSE OF REVIEW: Pediatric skin and soft tissue infections (SSTIs) constitute a significant number of office-based pediatric visits. With SSTIs on the rise, it is not only important to effectively treat the individual, but to do so appropriately and cost-consciously. In this article, we highlight new research related to the treatment of bacterial skin infections, molluscum contagiosum, and cutaneous warts, with the goal of guiding pediatricians in their practice against these common skin conditions. RECENT FINDINGS: Recent data supports the use of topical antibiotics for noncomplicated impetigo. Systemic antibiotics covering gram-positive cocci are recommended for complicated cases of impetigo and deeper nonpurulent SSTIs. Localized purulent bacterial SSTIs can be treated with incision and drainage alone but more systemic involvement warrants treatment with systemic antibiotics covering Staphylococcus aureus species, especially community acquired methicillin-resistant S. aureus. For the treatment of molluscum contagiosum, topical cantharidin has a high satisfaction rate among patients and providers. Potassium hydroxide solution is a potentially effective and cheap form of molluscum contagiosum treatment. Imiquimod, however, has an unfavorable efficacy and safety profile as a therapy for molluscum contagiosum. Regarding warts, high-risk human papilloma virus strains have been detected in cutaneous warts in children. SUMMARY: The high-risk human papilloma virus vaccine may play a role in treating pediatric cutaneous warts in the future, and topical squaric acid dibutylester may effectively treat recalcitrant warts. Finally, both molluscum contagiosum and warts have a high rate of resolution after an extended period of time without any intervention. PMID- 26900922 TI - MEF2C and EBF1 Co-regulate B Cell-Specific Transcription. AB - Hematopoietic stem cells are capable of self-renewal or differentiation along three main lineages: myeloid, erythroid, and lymphoid. One of the earliest lineage decisions for blood progenitor cells is whether to adopt the lymphoid or myeloid fate. Previous work had shown that myocyte enhancer factor 2C (MEF2C) is indispensable for the lymphoid fate decision, yet the specific mechanism of action remained unclear. Here, we have identified early B cell factor-1 (EBF1) as a co-regulator of gene expression with MEF2C. A genome-wide survey of MEF2C and EBF1 binding sites identified a subset of B cell-specific genes that they target. We also determined that the p38 MAPK pathway activates MEF2C to drive B cell differentiation. Mef2c knockout mice showed reduced B lymphoid-specific gene expression as well as increased myeloid gene expression, consistent with MEF2C's role as a lineage fate regulator. This is further supported by interaction between MEF2C and the histone deacetylase, HDAC7, revealing a likely mechanism to repress the myeloid transcription program. This study thus elucidates both activation and repression mechanisms, identifies regulatory partners, and downstream targets by which MEF2C regulates lymphoid-specific differentiation. PMID- 26900924 TI - Recoding a cocaine-place memory engram to a neutral engram in the hippocampus. AB - The hippocampus provides the brain's memory system with a subset of neurons holding a map-like representation of each environment experienced. We found in mice that optogenetic silencing those neurons active in an environment unmasked a subset of quiet neurons, enabling the emergence of an alternative map. When applied in a cocaine-paired environment, this intervention neutralized an otherwise long-lasting drug-place preference, showing that recoding a spatial memory engram can alleviate associated maladaptive behavior. PMID- 26900923 TI - Integrated genomics and proteomics define huntingtin CAG length-dependent networks in mice. AB - To gain insight into how mutant huntingtin (mHtt) CAG repeat length modifies Huntington's disease (HD) pathogenesis, we profiled mRNA in over 600 brain and peripheral tissue samples from HD knock-in mice with increasing CAG repeat lengths. We found repeat length-dependent transcriptional signatures to be prominent in the striatum, less so in cortex, and minimal in the liver. Coexpression network analyses revealed 13 striatal and 5 cortical modules that correlated highly with CAG length and age, and that were preserved in HD models and sometimes in patients. Top striatal modules implicated mHtt CAG length and age in graded impairment in the expression of identity genes for striatal medium spiny neurons and in dysregulation of cyclic AMP signaling, cell death and protocadherin genes. We used proteomics to confirm 790 genes and 5 striatal modules with CAG length-dependent dysregulation at the protein level, and validated 22 striatal module genes as modifiers of mHtt toxicities in vivo. PMID- 26900902 TI - Use of a Vaginal Ring Containing Dapivirine for HIV-1 Prevention in Women. AB - BACKGROUND: Antiretroviral medications that are used as prophylaxis can prevent acquisition of human immunodeficiency virus type 1 (HIV-1) infection. However, in clinical trials among African women, the incidence of HIV-1 infection was not reduced, probably because of low adherence. Longer-acting methods of drug delivery, such as vaginal rings, may simplify use of antiretroviral medications and provide HIV-1 protection. METHODS: We conducted a phase 3, randomized, double blind, placebo-controlled trial of a monthly vaginal ring containing dapivirine, a non-nucleoside HIV-1 reverse-transcriptase inhibitor, involving women between the ages of 18 and 45 years in Malawi, South Africa, Uganda, and Zimbabwe. RESULTS: Among the 2629 women who were enrolled, 168 HIV-1 infections occurred: 71 in the dapivirine group and 97 in the placebo group (incidence, 3.3 and 4.5 per 100 person-years, respectively). The incidence of HIV-1 infection in the dapivirine group was lower by 27% (95% confidence interval [CI], 1 to 46; P=0.046) than that in the placebo group. In an analysis that excluded data from two sites that had reduced rates of retention and adherence, the incidence of HIV 1 infection in the dapivirine group was lower by 37% (95% CI, 12 to 56; P=0.007) than that in the placebo group. In a post hoc analysis, higher rates of HIV-1 protection were observed among women over the age of 21 years (56%; 95% CI, 31 to 71; P<0.001) but not among those 21 years of age or younger (-27%; 95% CI, -133 to 31; P=0.45), a difference that was correlated with reduced adherence. The rates of adverse medical events and antiretroviral resistance among women who acquired HIV-1 infection were similar in the two groups. CONCLUSIONS: A monthly vaginal ring containing dapivirine reduced the risk of HIV-1 infection among African women, with increased efficacy in subgroups with evidence of increased adherence. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01617096 .). PMID- 26900925 TI - Fluorescent false neurotransmitter reveals functionally silent dopamine vesicle clusters in the striatum. AB - Neurotransmission at dopaminergic synapses has been studied with techniques that provide high temporal resolution, but cannot resolve individual synapses. To elucidate the spatial dynamics and heterogeneity of individual dopamine boutons, we developed fluorescent false neurotransmitter 200 (FFN200), a vesicular monoamine transporter 2 (VMAT2) substrate that selectively traces monoamine exocytosis in both neuronal cell culture and brain tissue. By monitoring electrically evoked Ca(2+) transients with GCaMP3 and FFN200 release simultaneously, we found that only a small fraction of dopamine boutons that exhibited Ca(2+) influx engaged in exocytosis, a result confirmed with activity dependent loading of the endocytic probe FM1-43. Thus, only a low fraction of striatal dopamine axonal sites with uptake-competent VMAT2 vesicles are capable of transmitter release. This is consistent with the presence of functionally 'silent' dopamine vesicle clusters and represents, to the best of our knowledge, the first report suggestive of presynaptically silent neuromodulatory synapses. PMID- 26900926 TI - Explicit information for category-orthogonal object properties increases along the ventral stream. AB - Extensive research has revealed that the ventral visual stream hierarchically builds a robust representation for supporting visual object categorization tasks. We systematically explored the ability of multiple ventral visual areas to support a variety of 'category-orthogonal' object properties such as position, size and pose. For complex naturalistic stimuli, we found that the inferior temporal (IT) population encodes all measured category-orthogonal object properties, including those properties often considered to be low-level features (for example, position), more explicitly than earlier ventral stream areas. We also found that the IT population better predicts human performance patterns across properties. A hierarchical neural network model based on simple computational principles generates these same cross-area patterns of information. Taken together, our empirical results support the hypothesis that all behaviorally relevant object properties are extracted in concert up the ventral visual hierarchy, and our computational model explains how that hierarchy might be built. PMID- 26900928 TI - Analyses of transcriptome sequences reveal multiple ancient large-scale duplication events in the ancestor of Sphagnopsida (Bryophyta). AB - The goal of this research was to investigate whether there has been a whole genome duplication (WGD) in the ancestry of Sphagnum (peatmoss) or the class Sphagnopsida, and to determine if the timing of any such duplication(s) and patterns of paralog retention could help explain the rapid radiation and current ecological dominance of peatmosses. RNA sequencing (RNA-seq) data were generated for nine taxa in Sphagnopsida (Bryophyta). Analyses of frequency plots for synonymous substitutions per synonymous site (Ks ) between paralogous gene pairs and reconciliation of 578 gene trees were conducted to assess evidence of large scale or genome-wide duplication events in each transcriptome. Both Ks frequency plots and gene tree-based analyses indicate multiple duplication events in the history of the Sphagnopsida. The most recent WGD event predates divergence of Sphagnum from the two other genera of Sphagnopsida. Duplicate retention is highly variable across species, which might be best explained by local adaptation. Our analyses indicate that the last WGD could have been an important factor underlying the diversification of peatmosses and facilitated their rise to ecological dominance in peatlands. The timing of the duplication events and their significance in the evolutionary history of peat mosses are discussed. PMID- 26900927 TI - Hyperactive somatostatin interneurons contribute to excitotoxicity in neurodegenerative disorders. AB - Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are overlapping neurodegenerative disorders whose pathogenesis remains largely unknown. Using TDP-43(A315T) mice, an ALS and FTD model with marked cortical pathology, we found that hyperactive somatostatin interneurons disinhibited layer 5 pyramidal neurons (L5-PNs) and contributed to their excitotoxicity. Focal ablation of somatostatin interneurons efficiently restored normal excitability of L5-PNs and alleviated neurodegeneration, suggesting a new therapeutic target for ALS and FTD. PMID- 26900931 TI - Optimizing Semantic Pointer Representations for Symbol-Like Processing in Spiking Neural Networks. AB - The Semantic Pointer Architecture (SPA) is a proposal of specifying the computations and architectural elements needed to account for cognitive functions. By means of the Neural Engineering Framework (NEF) this proposal can be realized in a spiking neural network. However, in any such network each SPA transformation will accumulate noise. By increasing the accuracy of common SPA operations, the overall network performance can be increased considerably. As well, the representations in such networks present a trade-off between being able to represent all possible values and being only able to represent the most likely values, but with high accuracy. We derive a heuristic to find the near-optimal point in this trade-off. This allows us to improve the accuracy of common SPA operations by up to 25 times. Ultimately, it allows for a reduction of neuron number and a more efficient use of both traditional and neuromorphic hardware, which we demonstrate here. PMID- 26900934 TI - Nerve-racking - apoptotic and non-apoptotic roles of caspases in the nervous system of Drosophila. AB - Studies using Drosophila as a model system have contributed enormously to our knowledge of caspase function and regulation. Caspases are best known as central executioners of apoptosis but also control essential physiological processes in a non-apoptotic manner. The Drosophila genome codes for seven caspases and in this review we provide an overview of current knowledge about caspase function in the nervous system. Caspases regulate neuronal death at all developmental stages and in various neuronal populations. In contrast, non-apoptotic roles are less well understood. The development of new genetically encoded sensors for caspase activity provides unprecedented opportunities to study caspase function in the nervous system in more detail. In light of these new tools we discuss the potential of Drosophila as a model to discover new apoptotic and non-apoptotic neuronal roles of caspases. PMID- 26900930 TI - Influential Factors for and Outcomes of Hospitalized Patients with Suicide Related Behaviors: A National Record Study in Taiwan from 1997-2010. AB - BACKGROUND: Investigating the factors related to suicide is crucial for suicide prevention. Psychiatric disorders, gender, socioeconomic status, and catastrophic illnesses are associated with increased risk of suicide. Most studies have typically focused on the separate influences of physiological or psychological factors on suicide-related behaviors, and have rarely used national data records to examine and compare the effects of major physical illnesses, psychiatric disorders, and socioeconomic status on the risk of suicide-related behaviors. OBJECTIVES: To identify the characteristics of people who exhibited suicide related behaviors and the multiple factors associated with repeated suicide related behaviors and deaths by suicide by examining national data records. DESIGN: This is a cohort study of Taiwan's national data records of hospitalized patients with suicide-related behaviors from January 1, 1997, to December 31, 2010. PARTICIPANTS: The study population included all people in Taiwan who were hospitalized with a code indicating suicide or self-inflicted injury (E950-E959) according to the International Classification of Disease, Ninth Revision, Clinical Modification. RESULTS: Self-poisoning was the most common method of self inflicted injury among hospitalized patients with suicide-related behaviors who used a single method. Those who were female, had been hospitalized for suicide related behaviors at a younger age, had a low income, had a psychiatric disorder (i.e., personality disorder, major depressive disorder, bipolar disorder, schizophrenia, alcohol-related disorder, or adjustment disorder), had a catastrophic illness, or had been hospitalized for suicide-related behaviors that involved two methods of self-inflicted injury had a higher risk of hospitalization for repeated suicide-related behaviors. Those who were male, had been hospitalized for suicide-related behaviors at an older age, had low income, had schizophrenia, showed repeated suicide-related behaviors, had a catastrophic illness, or had adopted a single lethal method had an increased risk of death by suicide. CONCLUSIONS: High-risk factors should be considered when devising suicide-prevention strategies. PMID- 26900929 TI - Development and Evaluation of Reverse Transcription-Loop-Mediated Isothermal Amplification (RT-LAMP) Assay Coupled with a Portable Device for Rapid Diagnosis of Ebola Virus Disease in Guinea. AB - Given the current absence of specific drugs or vaccines for Ebola virus disease (EVD), rapid, sensitive, and reliable diagnostic methods are required to stem the transmission chain of the disease. We have developed a rapid detection assay for Zaire ebolavirus based on reverse transcription-loop-mediated isothermal amplification (RT-LAMP) and coupled with a novel portable isothermal amplification and detection platform. The RT-LAMP assay is based on primer sets that target the untranscribed trailer region or nucleoprotein coding region of the viral RNA. The test could specifically detect viral RNAs of Central and West African Ebola virus strains within 15 minutes with no cross-reactivity to other hemorrhagic fever viruses and arboviruses, which cause febrile disease. The assay was evaluated using a total of 100 clinical specimens (serum, n = 44; oral swab, n = 56) collected from suspected EVD cases in Guinea. The specificity of this diagnostic test was 100% for both primer sets, while the sensitivity was 100% and 97.9% for the trailer and nucleoprotein primer sets, respectively, compared with a reference standard RT-PCR test. These observations suggest that our diagnostic assay is useful for identifying EVD cases, especially in the field or in settings with insufficient infrastructure. PMID- 26900935 TI - Gait Performance and Use of Mental Imagery as a Measure of Disease Progression in Amyotrophic Lateral Sclerosis. AB - OBJECTIVE: Gait and balance are key determinants of disease status in amyotrophic lateral sclerosis (ALS). This study aims at testing the relationship between the imagery of gait and disability in patients with ALS. METHODS: Twenty-five consecutive patients (63.8 +/- 2.4 years; 52% female) performed the timed up and go (TUG) test and a validated imagined version of the TUG between March 2011 and May 2012. The revised ALS functional rating score (ALSFRS-R) was assessed simultaneously. RESULTS: The mean duration of TUG (16.7 +/- 2.2 s) was significantly longer than imagined TUG (iTUG; 10.5 +/- 1.4 s, p < 0.001). The TUG (R2 = 0.40, p = 0.001) and the iTUG (R2 = 0.30, p = 0.007) were significantly associated with results of the ALSFRS-R score (37.0 +/- 7.3) as well as with muscle strength in arms (TUG R2 = 0.42, p < 0.001, iTUG R2 = 0.38, p = 0.001) and legs (TUG R2 = 0.47, p < 0.001, iTUG R2 = 0.46, p < 0.001). TUG and iTUG increased with age (TUG R2 = 0.18, p = 0.04, iTUG R2 = 0.12, p = 0.05). CONCLUSION: ALS patients performed the imagined gait faster than the real gait. Both TUG and iTUG correlated with disability measured by the ALSFRS-R score and by muscle strength. These inexpensive and easy clinical tests represent promising tools in clinical practice to study gait in ALS. PMID- 26900932 TI - The Patient-Provider Relationship Is Associated with Hepatitis C Treatment Eligibility: A Prospective Mixed-Methods Cohort Study. AB - Hepatitis C virus (HCV) treatment has the potential to cure the leading cause of cirrhosis and hepatocellular carcinoma. However, only those deemed eligible for treatment have the possibility of this cure. Therefore, understanding the determinants of HCV treatment eligibility is critical. Given that effective communication with and trust in healthcare providers significantly influences treatment eligibility decisions in other diseases, we aimed to understand patient provider interactions in the HCV treatment eligibility process. This prospective cohort study was conducted in the VA Pittsburgh Healthcare System. Patients were recruited after referral for gastroenterology consultation for HCV treatment with interferon and ribavirin. Consented patients completed semi-structured interviews and validated measures of depression, substance and alcohol use, and HCV knowledge. Two coders analyzed the semi-structured interviews. Factors associated with patient eligibility for interferon-based therapy were assessed using multivariate logistic regression. Of 339 subjects included in this analysis, only 56 (16.5%) were deemed eligible for HCV therapy by gastroenterology (GI) providers. In the multivariate logistic regression, patients who were older (OR = 0.96, 95%CI = 0.92-0.99, p = .049), reported concerns about the GI provider (OR = 0.40, 95%CI = 0.10-0.87, p = 0.02) and had depression symptoms (OR = 0.32, 95%CI = 0.17-0.63, p = 0.001) were less likely to be eligible. Patients described barriers that included feeling stigmatized and poor provider interpersonal or communication skills. In conclusion, we found that patients' perceptions of the relationship with their GI providers were associated with treatment eligibility. Establishing trust and effective communication channels between patients and providers may lower barriers to potential HCV cure. PMID- 26900936 TI - Advanced Analysis of Pharmaco-EEG Data in Humans. AB - Pharmaco-electroencephalography (EEG) is a non-invasive method used to assess the effects of pharmacological compounds on the central nervous system by processing the EEG signals which directly reveal the spontaneous synchronised postsynaptic neuronal activity of the cortex with high temporal resolution. The International Pharmaco-Encephalography Society (IPEG) has recently published guidelines, which were produced by a global panel of EEG experts, with the goal to increase the standardisation of pharmaco-EEG studies in human subjects and facilitate the comparability of data across laboratories, thus enabling data-pooling and meta analyses. The recommended standard experimental procedure is to measure EEG activity under vigilance-controlled and resting conditions. The IPEG guidelines thoroughly present the technical details and therefore constitute a robust reference. The complementary aim of the present paper is to focus on practical aspects, pitfalls and precautions to be considered when processing pharmaco-EEG data by covering the following topics: (1) investigate the stability and reliability of 5-min EEG recordings under both vigilance-controlled and resting conditions; (2) assess the spontaneous time-dependent changes in spectral activity over time, and (3) apply the data-processing strategies suggested in the pharmaco-EEG guidelines and designed to optimally capture drug effects. For this purpose, the EEG data from a randomised, double-blind, crossover trial aimed at comparing the effect of diazepam (10 mg) and placebo in 16 healthy male volunteers is used to illustrate the discussion of the processing techniques and difficulties commonly faced when analysing pharmaco-EEG data. PMID- 26900933 TI - Stage-dependent effects of exogenous TRAIL on atherogenesis: role of ER stress mediated sensitization of macrophage apoptosis. AB - Deletion of the gene of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in apolipoprotein E-deficient (ApoE-/-) mice increased atherosclerosis. However, the effect of TRAIL at a supra-physiological level on early atherogenesis is unknown. ApoE-/- mice were divided into Early (high-fat diet with concomitant TRAIL treatment for 4 weeks) and Late (high-fat diet for 16 weeks with TRAIL being given during the last 4 weeks) groups. It was found that TRAIL stimulated atherogenesis in the Early group but not in the Late group. TRAIL did not change the intra-plaque macrophage content in Early group, but decreased it in the Late group. In cultured macrophages, induction of endoplasmic reticulum (ER) stress increased death receptor 5 (DR5) expression and TRAIL induced apoptosis, which were mediated by the transcription factor CCAAT/enhancer binding protein homologous protein (CHOP). The expression levels of CHOP, 78 kDa glucose-regulated protein (GRP78) and DR5 were all elevated in the Late group. TRAIL treatment in vivo also increased intra-plaque apoptotic only in Late lesions. Moreover, the chemical chaperone 4-phenylbutyrate blocked the development of ER stress and upregulation of DR5 in Late lesions in vivo. In conclusion, TRAIL at a supra-physiological level has a stimulatory effect on early atherogenesis, but not in the advanced lesions. The differential effects of TRAIL may be related to differences in ER stress, DR5 expression, and the sensitivity of macrophage apoptosis in response to TRAIL in early versus advanced lesions. The results presented here raise the possibility that treatment with exogenous TRAIL as a therapeutic agent may be detrimental in patients with increased risk of atherosclerosis. PMID- 26900937 TI - Temperature Mediated Morphological Transition during Drying of Spray Colloidal Droplets. AB - Understanding how a tiny dilute evaporative colloidal spray droplet gets transformed into a microgranule with a characteristic morphology is crucial from scientific as well as technological points of view. In the present work, it is demonstrated that the morphology and the size distribution of the microcapsules can be tuned simply by adjusting the drying temperature. Shape and size of the capsules are quantified at four different drying temperatures. It is shown that the morphology transits gradually from sphere to toroid with increasing temperature keeping the average volume-fraction of the correlated nanoparticles nearly unaffected for the synthesized granules. A plausible mechanism for the chronological pathway of such morphological transformation is illustrated. Computer simulation corroborates the experimentally observed morphological transition. The variation in hollowness and buckling tendency of the capsules are elucidated by scattering and imaging techniques. PMID- 26900938 TI - Strongly enhanced photoluminescence in nanostructured monolayer MoS2 by chemical vapor deposition. AB - Two-dimensional (2D) layered molybdenum disulfide (MoS2) has become a very promising candidate semiconducting material for future optoelectronic devices, owing to its unique properties. However, monolayer MoS2 is still a weak photon emitter, compared with other direct band gap semiconductors, which requires extra techniques or complicated steps to enhance its photon emission efficiency. Here, we demonstrated that nanostructured monolayer MoS2, produced by one-step chemical vapor deposition (CVD) growth, shows highly enhanced PL emission. The effective enhancement factor could be up to ~43. Our results open the door to manipulating the optical properties of future devices by using nanostructured 2D monolayers. PMID- 26900939 TI - Sulindac Sulfide Induces the Formation of Large Oligomeric Aggregates of the Alzheimer's Disease Amyloid-beta Peptide Which Exhibit Reduced Neurotoxicity. AB - Alzheimer's disease is characterized by deposition of the amyloid beta-peptide (Abeta) in brain tissue of affected individuals. In recent years, many potential lead structures have been suggested that can potentially be used for diagnosis and therapy. However, the mode of action of these compounds is so far not understood. Among these small molecules, the nonsteroidal anti-inflammatory drug (NSAID) sulindac sulfide received a lot of attention. In this manuscript, we characterize the interaction between the monomeric Abeta peptide and the NSAID sulindac sulfide. We find that sulindac sulfide efficiently depletes the pool of toxic oligomers by enhancing the rate of fibril formation. In vitro, sulindac sulfide forms colloidal particles which catalyze the formation of fibrils. Aggregation is immediate, presumably by perturbing the supersaturated Abeta solution. We find that sulindac sulfide induced Abeta aggregates are structurally homogeneous. The C-terminal part of the peptide adopts a beta-sheet structure, whereas the N-terminus is disordered. The salt bridge between D23 and K28 is present, similar as in wild type fibril structures. (13)C-(19)F transferred echo double resonance experiments suggest that sulindac sulfide colocalizes with the Abeta peptide in the aggregate. PMID- 26900940 TI - Physical Activity and Children in Care: A Scoping Review of Barriers, Facilitators, and Policy for Disadvantaged Youth. AB - BACKGROUND: It is argued that regular engagement in physical activity (PA) has the potential to mitigate the negative health and educational outcomes that disadvantaged children living in care frequently face. However, little is currently known about children in care's participation in PA. This scoping review primarily aimed to identify barriers and facilitators to PA participation for children in care. METHODS: The main phases of the scoping review were 1) identifying relevant studies; 2) selecting studies based on predefined inclusion criteria; 3) charting the data; and 4) collating, summarizing, and reporting the results. All relevant studies were included in the review regardless of methodological quality and design. RESULTS: The 7 articles that met the inclusion criteria were published between 1998 and 2013 and conducted in the USA (3), England (2), and Norway (2). A social ecological model was incorporated to map results against levels of influence. CONCLUSIONS: Various factors influence PA engagement for children in care. Barriers include low self-efficacy, instability of their social environment, which impacts on schooling and maintaining friendship groups, and, specific institutional practices and policies that may prevent access to PA. Before fully considering policy implications, further research with children in care is warranted in this area. PMID- 26900941 TI - Golden angle dual-inversion recovery acquisition coupled with a flexible time resolved sparse reconstruction facilitates sequence timing in high-resolution coronary vessel wall MRI at 3 T. AB - PURPOSE: The need for performing dual-inversion recovery (DIR) coronary vessel wall MRI in correspondence to minimal cardiac motion and optimal blood signal nulling is a major challenge. We propose to address this hurdle by combining DIR with a prolonged acquisition window in conjunction with a golden angle radial trajectory and k-t sparse sensitivity encoding (SENSE) reconstruction to enable a flexible a-posteriori selection of optimized imaging parameters. METHODS: Coronary vessel wall data acquisition was performed with DIR golden angle radial imaging in n=15 healthy subjects. Images reconstructed using k-t sparse SENSE and different reconstruction window settings were quantitatively (vessel wall conspicuity, thickness, acquisition, and reconstruction window settings) compared with those obtained with more conventional radial DIR imaging. RESULTS: A flexible retrospective selection of the reconstruction window width and position improved vessel wall conspicuity with respect to baseline acquisitions (P < 0.01). Vessel wall thickness remained unchanged (P = nonsignificant (NS)). Temporal window widths were similar for both approaches (P = NS), yet their position within the cardiac cycle differed significantly (P < 0.02). CONCLUSIONS: A flexible DIR coronary vessel wall MRI technique that alleviates constraints associated with sophisticated sequence timing was proposed. When compared with a more conventional approach, the technique significantly improved image quality. Magn Reson Med 77:961-969, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 26900942 TI - Structure prediction and analysis of neuraminidase sequence variants. AB - Analyzing protein structure has become an integral aspect of understanding systems of biochemical import. The laboratory experiment endeavors to introduce protein folding to ascertain structures of proteins for which the structure is unavailable, as well as to critically evaluate the quality of the prediction obtained. The model system used is the highly mutable influenza virus protein neuraminidase, which is the key target in the development of therapeutics. In light of recent pandemics, understanding how mutations confer drug resistance, which translates at the molecular level to understanding how different sequence variants differ, constitutes an area of great interest because of the ramifications in public health. This lab targets upper level undergraduate biochemistry students, and aims to introduce tools to be used to explore protein folding and protein visualization in the context of the neuraminidase case study. Students proceed to critically evaluate the folded models by comparison with crystallographic structures. When validity is established, they fold a neuraminidase sequence for which a structure is not available. Through structural alignment and visual inspection of the 150 loop, students gain molecular insight into two possible conformations of the protein, which are actively being studied. Folding the third chosen sequence mimics a true research environment in allowing students to generate a structure from a sequence for which a structure was not previously available, and to assess whether their particular variant has an open or closed loop. From this vantage, they are then challenged to speculate about the connection between loop conformation and drug susceptibility. (c) 2016 by The International Union of Biochemistry and Molecular Biology, 44(4):361-376, 2016. PMID- 26900943 TI - Androgen therapy in Fanconi anemia: A retrospective analysis of 30 years in Germany. AB - A substantial number of individuals with Fanconi anemia (FA) develop bone marrow failure and are treated with androgen therapy in order to increase blood counts. The authors retrospectively identified 70 patients who received androgen therapy any time between July 1976 and September 2014. Among these patients, 37 had medical records for analysis. Twenty-five of the 37 (68%) patients had response in hemoglobin level (n = 25), platelet count (n = 21), and/or absolute neutrophil count (n = 13). The median rise in hemoglobin was 6.5 mg/dL, platelet count 70,000/mm(3), and absolute neutrophil count (ANC) 1530/MUL. The majority of patients (n = 22) had a response in 2 or more blood parameters. Reasons for discontinuation of therapy included development of cytogenetic aberrations (n = 9), lack of response (n = 7), hepatic adenoma (n = 6), progression to myelodysplastic syndrome/acute myeloid leukemia (n = 3), stabilization of blood parameters (n = 3), resolution of cytopenia secondary to mosaicism (n = 1), virilization (n = 1), development of anogenital carcinoma (n = 1), inaccessibility of medication (n = 1), and unknown (n = 1). Four patients at last follow-up remain on androgen therapy. These results highlight that androgen therapy can significantly improve blood counts for many FA patients, but progression of underlying bone marrow disease and development of liver adenomas requires careful monitoring. PMID- 26900944 TI - The Economic Impact of Eradicating Peste des Petits Ruminants: A Benefit-Cost Analysis. AB - Peste des petits ruminants (PPR) is an important cause of mortality and production loss among sheep and goats in the developing world. Despite control efforts in a number of countries, it has continued to spread across Africa and Asia, placing an increasing burden on the livelihoods of livestock keepers and on veterinary resources in affected countries. Given the similarities between PPR and rinderpest, and the lessons learned from the successful global eradication of rinderpest, the eradication of PPR seems appealing, both eliminating an important disease and improving the livelihoods of the poor in developing countries. We conducted a benefit-cost analysis to examine the economic returns from a proposed programme for the global eradication of PPR. Based on our knowledge and experience, we developed the eradication strategy and estimated its costs. The benefits of the programme were determined from (i) the averted mortality costs, based on an analysis of the literature, (ii) the downstream impact of reduced mortality using a social accounting matrix, and (iii) the avoided control costs based on current levels of vaccination. The results of the benefit-cost analysis suggest strong economic returns from PPR eradication. Based on a 15-year programme with total discounted costs of US$2.26 billion, we estimate discounted benefits of US$76.5 billion, yielding a net benefit of US$74.2 billion. This suggests a benefit cost ratio of 33.8, and an internal rate of return (IRR) of 199%. As PPR mortality rates are highly variable in different populations, we conducted a sensitivity analysis based on lower and higher mortality scenarios. All the scenarios examined indicate that investment in PPR eradication would be highly beneficial economically. Furthermore, removing one of the major constraints to small ruminant production would be of considerable benefit to many of the most vulnerable communities in Africa and Asia. PMID- 26900945 TI - Effects of Hospital Workers' Friendship Networks on Job Stress. AB - BACKGROUND: This study attempted to identify the sources of job stress according to job position and investigate how friendship networks affect job stress. METHODS: Questionnaires based on The Health Professions Stress Inventory (HPSI) developed by Wolfgang experienced by healthcare providers were collected from 420 nurses, doctors and radiological technologists in two general hospitals in Korea by a multistage cluster sampling method. Multiple regression analysis was used to examine the effects of friendship networks on job stress after controlling for other factors. RESULTS: The severity of job stress differed according to level of job demands (p = .006); radiologic technologists experienced the least stress (45.4), nurses experienced moderate stress (52.4), and doctors experienced the most stress (53.6). Those with long-term friendships characterized by strong connections reported lower levels of stress than did those with weak ties to friends among nurses (1.3, p < .05) and radiological technologists (11.4, p < .01). The degree of cohesion among friends had a positive impact on the level of job stress experienced by nurses (8.2, p < .001) and radiological technologists (14.6, p < .1). Doctors who participated in workplace alumni meetings scored higher than those who did not. However, those who participated in alumni meetings outside the workplace showed the opposite tendency, scoring 9.4 (p < .05) lower than those who did not. The resources from their friendship network include both information and instrumental support. As most radiological technologists were male, their instrumental support positively affected their job stress (9.2, p < .05). Life information support was the primary positive contributor to control of nurses' (4.1, p < .05), radiological technologists' (8.0, p < .05) job stress. CONCLUSION: The strength and density of such friendship networks were related to job stress. Life information support from their friendship network was the primary positive contributor to control of job stress. PMID- 26900946 TI - An Oxalyl-CoA Dependent Pathway of Oxalate Catabolism Plays a Role in Regulating Calcium Oxalate Crystal Accumulation and Defending against Oxalate-Secreting Phytopathogens in Medicago truncatula. AB - Considering the widespread occurrence of oxalate in nature and its broad impact on a host of organisms, it is surprising that so little is known about the turnover of this important acid. In plants, oxalate oxidase is the most well studied enzyme capable of degrading oxalate, but not all plants possess this activity. Recently, an Acyl Activating Enzyme 3 (AAE3), encoding an oxalyl-CoA synthetase, was identified in Arabidopsis. AAE3 has been proposed to catalyze the first step in an alternative pathway of oxalate degradation. Whether this enzyme and proposed pathway is important to other plants is unknown. Here, we identify the Medicago truncatula AAE3 (MtAAE3) and show that it encodes an oxalyl-CoA synthetase activity exhibiting high activity against oxalate with a Km = 81 +/- 9 MUM and Vmax = 19 +/- 0.9 MUmoles min-1mg protein-1. GFP-MtAAE3 localization suggested that this enzyme functions within the cytosol of the cell. Mtaae3 knock down line showed a reduction in its ability to degrade oxalate into CO2. This reduction in the capacity to degrade oxalate resulted in the accumulation of druse crystals of calcium oxalate in the Mtaae3 knock-down line and an increased susceptibility to oxalate-secreting phytopathogens such as Sclerotinia sclerotiorum. Taken together, these results suggest that AAE3 dependent turnover of oxalate is important to different plants and functions in the regulation of tissue calcium oxalate crystal accumulation and in defense against oxalate secreting phytopathogens. PMID- 26900948 TI - Exploring Market State and Stock Interactions on the Minute Timescale. AB - A stock market is a non-stationary complex system. The stock interactions are important for understanding the state of the market. However, our knowledge on the stock interactions on the minute timescale is limited. Here we apply the random matrix theory and methods in complex networks to study the stock interactions and sector interactions. Further, we construct a new kind of cross correlation matrix to investigate the correlation between the stock interactions at different minutes within one trading day. Based on 50 million minute-to-minute price data in the Shanghai stock market, we discover that the market states in the morning and afternoon are significantly different. The differences mainly exist in three aspects, i.e. the co-movement of stock prices, interactions of sectors and correlation between the stock interactions at different minutes. In the afternoon, the component stocks of sectors are more robust and the structure of sectors is firmer. Therefore, the market state in the afternoon is more stable. Furthermore, we reveal that the information of the sector interactions can indicate the financial crisis in the market, and the indicator based on the empirical data in the afternoon is more effective. PMID- 26900949 TI - The role of low acid load in vegetarian diet on bone health: a narrative review. AB - Vegetarian and vegan diets contain low amounts of protein and calcium. For this reason they are supposed to cause low bone mineral density (BMD) and osteoporosis. But this is not the case, except for vegans with a particularly low calcium intake. The absence of osteoporosis or low BMD can be explained by the low acid load of these diets. Nutritional acid load is negatively correlated with bone mineral density (BMD) and positively with fracture risk. Low acid load is correlated with lower bone resorption and higher BMD. It is linked to high intake of potassium-rich nutrients, such as fruits and vegetables, as found in vegetarian diets. The total nutritional acid load, which not only depends on the potassium content of the nutrition, was recently assessed in several studies on vegetarian and vegan diets and was found to be very low or absent, while the diet of Western-style omnivores produces daily 50 to 70 mEq of acid. This might be an important factor for the protection of vegetarians from osteoporosis. PMID- 26900947 TI - Suboptimal Larval Habitats Modulate Oviposition of the Malaria Vector Mosquito Anopheles coluzzii. AB - Selection of oviposition sites by gravid females is a critical behavioral step in the reproductive cycle of Anopheles coluzzii, which is one of the principal Afrotropical malaria vector mosquitoes. Several studies suggest this decision is mediated by semiochemicals associated with potential oviposition sites. To better understand the chemosensory basis of this behavior and identify compounds that can modulate oviposition, we examined the generally held hypothesis that suboptimal larval habitats give rise to semiochemicals that negatively influence the oviposition preference of gravid females. Dual-choice bioassays indicated that oviposition sites conditioned in this manner do indeed foster significant and concentration dependent aversive effects on the oviposition site selection of gravid females. Headspace analyses derived from aversive habitats consistently noted the presence of dimethyl disulfide (DMDS), dimethyl trisulfide (DMTS) and 6 methyl-5-hepten-2-one (sulcatone) each of which unitarily affected An. coluzzii oviposition preference. Electrophysiological assays across the antennae, maxillary palp, and labellum of gravid An. coluzzii revealed differential responses to these semiochemicals. Taken together, these findings validate the hypothesis in question and suggest that suboptimal environments for An. coluzzii larval development results in the release of DMDS, DMTS and sulcatone that impact the response valence of gravid females. PMID- 26900950 TI - Hepatic carcinoma-associated fibroblasts induce IDO-producing regulatory dendritic cells through IL-6-mediated STAT3 activation. AB - Although carcinoma-associated fibroblasts (CAFs) in tumor microenvironments have a critical role in immune cell modulation, their effects on the generation of regulatory dendritic cells (DCs) are still unclear. In this study, we initially show that CAFs derived from hepatocellular carcinoma (HCC) tumors facilitate the generation of regulatory DCs, which are characterized by low expression of costimulatory molecules, high suppressive cytokines production and enhanced regulation of immune responses, including T-cell proliferation impairment and promotion of regulatory T-cell (Treg) expansion via indoleamine 2,3-dioxygenase (IDO) upregulation. Our findings also indicate that STAT3 activation in DCs, as mediated by CAF-derived interleukin (IL)-6, is essential to IDO production. Moreover, IDO inhibitor, STAT3 and IL-6 blocking antibodies can reverse this hepatic CAF-DC regulatory function. Therefore, our results provide new insights into the mechanisms by which CAFs induce tumor immune escape as well as a novel cancer immunotherapeutic approach (for example, targeting CAFs, IDO or IL-6). PMID- 26900951 TI - The T-box transcription factor 3 is a promising biomarker and a key regulator of the oncogenic phenotype of a diverse range of sarcoma subtypes. AB - Sarcomas represent a complex group of malignant neoplasms of mesenchymal origin and their heterogeneity poses a serious diagnostic and therapeutic challenge. There is therefore a need to elucidate the molecular mechanisms underpinning the pathogenesis of the more than 70 distinguishable sarcoma subtypes. The transcription factor TBX3, a critical developmental regulator, is overexpressed in several cancers of epithelial origin where it contributes to tumorigenesis by different molecular mechanisms. However, the status and role of TBX3 in sarcomas have not been reported. Here we show that a diverse subset of soft tissue and bone sarcoma cell lines and patient-derived sarcoma tissues express high levels of TBX3. We further explore the significance of this overexpression using a small interferring RNA approach and demonstrate that TBX3 promotes the migratory ability of chondrosarcoma, rhabdomyosarcoma and liposarcoma cells but inhibits fibrosarcoma cell migration. This suggested that TBX3 may play a key role in the development of different sarcoma subtypes by functioning as either an oncoprotein or as a brake to prevent tumour progression. To further explore this, TBX3 knockdown and overexpression cell culture models were established using chondrosarcoma and fibrosarcoma cells as representatives of each scenario, and the resulting cells were characterized with regard to key features of tumorigenesis. Results from in vitro and in vivo assays reveal that, while TBX3 promotes substrate-dependent and -independent cell proliferation, migration and tumour formation in chondrosarcoma cells, it discourages fibrosarcoma formation. Our findings provide novel evidence linking TBX3 to cancers of mesenchymal origin. Furthermore, we show that TBX3 may be a biomarker for the diagnosis of histologically dynamic sarcoma subtypes and that it impacts directly on their oncogenic phenotype. Indeed, we reveal that TBX3 may exhibit oncogene or tumour suppressor activity in sarcomas, which suggests that its role in cancer progression may rely on cellular context. PMID- 26900953 TI - High-Pressure Synthesis, Crystal Structure, and Magnetic Properties of Sr2MnO3F: A New Member of Layered Perovskite Oxyfluorides. AB - We have successfully synthesized Sr2MnO3F, a new layered perovskite oxyfluoride with a n = 1 Ruddlesden-Popper-type structure using a high-pressure, high temperature method. Structural refinements against synchrotron X-ray diffraction data collected from manganese oxyfluoride demonstrated that it crystallizes in a tetragonal cell with the space group I4/mmm, in which the Mn cation is located at the octahedral center position. This is in stark contrast to the related oxyhalides that have square-pyramidal coordination such as Sr2MO3X (M = Fe, Co, Ni; X = F, Cl) and Sr2MnO3Cl. There was no evidence of O/F site order, but close inspection of the anion environment centered at the Mn cation on the basis of bond-valence-sum calculation suggested preferential occupation of the apical sites by the F ion with one oxide ion in a random manner. Magnetic susceptibility and heat capacity measurements revealed an antiferromagnetic ordering at 133 K (=TN), which is much higher than that of the chloride analogue with corrugated MnO2 planes (TN = 80 K). PMID- 26900954 TI - Antistaphylococcal Prenylated Acylphoroglucinol and Xanthones from Kielmeyera variabilis. AB - Bioactivity-guided fractionation of the EtOH extract of the branches of Kielmeyera variabilis led to the isolation of a new acylphoroglucinol (1), which was active against all the MRSA strains tested herein, with pronounced activity against strain EMRSA-16. Compound 1 displayed an MIC of 0.5 mg/L as compared with an MIC of 128 mg/L for the control antibiotic norfloxacin. The structure of the new compound was elucidated by 1D and 2D NMR spectroscopic analysis and mass spectrometry, and experimental and calculated ECD were used to determine the absolute configurations. The compounds beta-sitosterol (2), stigmasterol (3), ergost-5-en-3-ol (4), and osajaxanthone (5) also occurred in the n-hexane fraction. The EtOAc fraction contained nine known xanthones: 3,6-dihydroxy-1,4,8 trimethoxyxanthone (6), 3,5-dihydroxy-4-methoxyxanthone (7), 3,4-dihydroxy-6,8 dimethoxyxanthone (8), 3,4-dihydroxy-2-methoxyxanthone (9), 5-hydroxy-1,3 dimethoxyxanthone (10), 4-hydroxy-2,3-dimethoxyxanthone (11), kielcorin (12), 3 hydroxy-2-methoxyxanthone (13), and 2-hydroxy-1-methoxyxanthone (14), which showed moderate to low activity against the tested MRSA strains. PMID- 26900955 TI - Kinetic barriers in transdifferentiation. PMID- 26900956 TI - Foot pedal-controlled CT review during functional endoscopic sinus surgery. PMID- 26900952 TI - Understanding cachexia as a cancer metabolism syndrome. AB - Metabolic reprogramming occurs in tumors to foster cancer cell proliferation, survival and metastasis, but as well at a systemic level affecting the whole organism, eventually leading to cancer cachexia. Indeed, as cancer cells rely on external sources of nitrogen and carbon skeleton to grow, systemic metabolic deregulation promoting tissue wasting and metabolites mobilization ultimately supports tumor growth. Cachectic patients experience a wide range of symptoms affecting several organ functions such as muscle, liver, brain, immune system and heart, collectively decreasing patients' quality of life and worsening their prognosis. Moreover, cachexia is estimated to be the direct cause of at least 20% of cancer deaths. The main aspect of cachexia syndrome is the unstoppable skeletal muscle and fat storage wasting, even with an adequate caloric intake, resulting in nutrient mobilization - both directly as lipid and amino acids and indirectly as glucose derived from the exploitation of liver gluconeogenesis - that reaches the tumor through the bloodstream. From a metabolic standpoint, cachectic host develops a wide range of dysfunctions, from increased insulin and IGF-1 resistance to induction of mitochondrial uncoupling proteins and fat tissue browning resulting in an increased energy expenditure and heat generation, even at rest. For a long time, cachexia has been merely considered an epiphenomenon of end-stage tumors. However, in specific tumor types, such as pancreatic cancers, it is now clear that patients present markers of tissue wasting at a stage in which tumor is not yet clinically detectable, and that host amino acid supply is required for tumor growth. Indeed, tumor cells actively promote tissue wasting by secreting specific factors such as parathyroid hormone-related protein and micro RNAs. Understanding the molecular and metabolic mediators of cachexia will not only advance therapeutic approaches against cancer, but also improve patients' quality of life. PMID- 26900957 TI - Race Guides Attention in Visual Search. AB - It is known that faces are rapidly and even unconsciously categorized into social groups (black vs. white, male vs. female). Here, I test whether preferences for specific social groups guide attention, using a visual search paradigm. In Experiment 1 participants searched displays of neutral faces for an angry or frightened target face. Black target faces were detected more efficiently than white targets, indicating that black faces attracted more attention. Experiment 2 showed that attention differences between black and white faces were correlated with individual differences in automatic race preference. In Experiment 3, using happy target faces, the attentional preference for black over white faces was eliminated. Taken together, these results suggest that automatic preferences for social groups guide attention to individuals from negatively valenced groups, when people are searching for a negative emotion such as anger or fear. PMID- 26900959 TI - Nickel-Doped La0.8Sr0.2Mn(1-x)Ni(x)O3 Nanoparticles Containing Abundant Oxygen Vacancies as an Optimized Bifunctional Catalyst for Oxygen Cathode in Rechargeable Lithium-Air Batteries. AB - In this work, Ni-doped manganite perovskite oxides (La0.8Sr0.2Mn(1-x)Ni(x)O3, x = 0.2 and 0.4) and undoped La0.8Sr0.2MnO3 were synthesized via a general and facile sol-gel route and used as bifunctional catalysts for oxygen cathode in rechargeable lithium-air batteries. The structural and compositional characterization results showed that the obtained La0.8Sr0.2Mn(1-x)Ni(x)O3 (x = 0.2 and 0.4) contained more oxygen vacancies than did the undoped La0.8Sr0.2MnO3 as well as a certain amount of Ni(3+) (eg = 1) on their surface. The Ni-doped La0.8Sr0.2Mn(1-x)Ni(x)O3 (x = 0.2 and 0.4) was provided with higher bifunctional catalytic activities than that of the undoped La0.8Sr0.2MnO3. In particular, the La0.8Sr0.2Mn0.6Ni0.4O3 had a lower total over potential between the oxygen evolution reaction and the oxygen reduction reaction than that of the La0.8Sr0.2MnO3, and the value is even comparable to that of the commercial Pt/C yet is provided with a much reduced cost. In the lithium-air battery, oxygen cathodes containing the La0.8Sr0.2Mn0.6Ni0.4O3 catalyst delivered the optimized electrochemical performance in terms of specific capacity and cycle life, and a reasonable reaction mechanism was given to explain the improved performance. PMID- 26900958 TI - Changes in Olfactory Bulb Volume in Parkinson's Disease: A Systematic Review and Meta-Analysis. AB - OBJECTIVE: The changes in olfactory bulb (OB) volume in Parkinson's disease (PD) patients have not yet been comprehensively evaluated. The purpose of this meta analysis was to explore whether the OB volume was significantly different between PD patients and healthy controls. METHODS: PubMed and Embase were searched up to March 6, 2015 with no language restrictions. Two independent reviewers screened eligible studies and extracted data on study characteristics and OB volume. Additionally, a systematic review and meta-analysis using a random-effects model were conducted. Publication bias was determined by using funnel plots and Begg's and Egger's tests. Subgroup analyses were performed to assess possible sources of heterogeneity. RESULTS: Six original case-control studies of 216 PD patients and 175 healthy controls were analyzed. The pooled weighted mean difference (WMD) in the OB volume between the PD patients and the healthy participants was -8.071 for the right OB and -10.124 for the left OB; these values indicated a significant difference among PD patients compared with healthy controls. In addition, a significant difference in the lateralized OB volume was observed in PD patients, with a pooled WMD of 1.618; these results indicated a larger right OB volume than left OB volume in PD patients. In contrast, no difference in the lateralized OB volume was found in healthy controls. No statistical evidence of publication bias among studies was found based on Egger's or Begg's tests. Sensitivity analyses revealed that the results were consistent and robust. CONCLUSIONS: Overall, both the left and the right OB volume were significantly smaller in PD patients than in healthy controls. However, significant heterogeneity and an insufficient number of studies underscore the need for further observational research. PMID- 26900960 TI - VEGF-C Is a Thyroid Marker of Malignancy Superior to VEGF-A in the Differential Diagnostics of Thyroid Lesions. AB - INTRODUCTION: Thyroid nodular goiter is one of the most common medical conditions affecting even over a half of adult population. The risk of malignancy is rather small but noticeable-estimated by numerous studies to be about 3-10%. The definite differentiation between benign and malignant ones is a vital issue in endocrine practice. The aim of the current study was to assess the expression of vascular endothelial growth factor A (VEGF-A) and VEGF-C on the mRNA level in FNAB washouts in case of benign and malignant thyroid nodules and to evaluate the diagnostic value of these markers of malignancy. MATERIALS AND METHODS: Patients undergoing fine-needle aspiration biopsy (FNAB) in our department between January 2013 and May 2014 were included. In case of all patients who gave the written consent, after ultrasonography (US) and fine-needle aspiration biopsy (FNAB) performed as routine medical procedure the needle was flushed with RNA Later solution, the washouts were frozen in -80 Celsius degrees. Expression of VEGF-A and VEGF-C and GADPH (reference gene) was assessed in washouts on the mRNA level using the real-time PCR technique. Probes of patients who underwent subsequent thyroidectomy and were diagnosed with differentiated thyroid cancer (DTC; proved by post-surgical histopathology) were analyzed. Similar number of patients with benign cytology were randomly selected to be a control group. RESULTS: Thirty one DTCs and 28 benign thyroid lesions were analyzed. Expression of VEGF-A was insignificantly higher in patients with DTCs (p = 0.13). Expression of VEGF-C was significantly higher in patients with DTC. The relative expression of VEGF-C (in comparison with GAPDH) was 0.0049 for DTCs and 0.00070 for benign lesions, medians - 0.0036 and 0.000024 respectively (p<0.0001). CONCLUSIONS: Measurement of expression VEGF-C on the mRNA level in washouts from FNAB is more useful than more commonly investigated VEGF-A. Measurement of VEGF-C in FNAB washouts do not allow for fully reliable differentiation of benign and malignant thyroid nodules and should be interpreted carefully. Further studies on larger groups are indicated. However, measurement of VEGF-C on mRNA level can bring important information without exposing patient for additional risk and invasive procedures. PMID- 26900961 TI - Perceived Comfort and Blinding Efficacy in Randomised Sham-Controlled Transcranial Direct Current Stimulation (tDCS) Trials at 2 mA in Young and Older Healthy Adults. AB - BACKGROUND: tDCS studies typically find that: lowest levels of comfort occur at stimulation-onset; young adult participants experience less comfort than older participants; and participants' blinding seems effective at low current strengths. At 2 mA conflicting results have been reported, questioning the effectiveness of blinding in sham-controlled paradigms using higher current strengths. Investigator blinding is rarely reported. OBJECTIVE: Using a protocol with 30 min of 2 mA stimulation we sought to: (a) investigate the level of perceived comfort in young and older adults, ranging in age from 19 to 29 years and 63 to 76 years, respectively; (b) test investigator and participant blinding; (c) assess comfort over a longer stimulation duration; (d) add to the literature on protocols using 2 mA current strength. METHODS: A two-session experiment was conducted where sham and active stimulation were administered to the frontal cortex at the F8/FP1 sites in a within-subjects manner. Levels of perceived comfort were measured, using a visual analogue scale, at the start and end of stimulation in young and older adults. Post-stimulation, participants and investigators judged whether or not active stimulation was used. RESULTS: Comfort scores were lower at stimulation onset in both age groups. Older adults reported: (i) more comfort than young participants overall; (ii) comparable levels of comfort in sham and active stimulation; (iii) significantly more comfort than the young participants during active stimulation. Stimulation mode was correctly identified above chance in the second of the two sessions; 65% of all participants correctly identified the stimulation mode, resulting in a statistical trend. Similarly, the experimenter correctly identified stimulation mode significantly above chance, with 62% of all investigator judgements correct across 120 judgements. CONCLUSIONS: Using 2 mA current strength over 30 minutes, tDCS stimulation comfort is lower at stimulation onset in young and older adults and, overall, lower for young participants. Investigators and participants may be able to identify active stimulation at above chance levels, although accuracy never exceeded 65% for either participants or the experimenter. Further research into blinding efficacy is recommended. PMID- 26900962 TI - Alteration of Pituitary Tumor Transforming Gene-1 Regulates Trophoblast Invasion via the Integrin/Rho-Family Signaling Pathway. AB - Trophoblast invasion ability is an important factor in early implantation and placental development. Recently, pituitary tumor transforming gene 1 (PTTG1) was shown to be involved in invasion and proliferation of cancer. However, the role of PTTG1 in trophoblast invasion remains unknown. Thus, in this study we analyzed PTTG1 expression in trophoblasts and its effect on trophoblast invasion activity and determined the mechanism through which PTTG1 regulates trophoblast invasion. Trophoblast proliferation and invasion abilities, regardless of PTTG1 expression, were analyzed by quantitative real-time polymerase chain reaction, fluorescence activated cell sorting analysis, invasion assay, western blot, and zymography after treatment with small interfering RNA against PTTG1 (siPTTG1). Additionally, integrin/Rho-family signaling in trophoblasts by PTTG1 alteration was analyzed. Furthermore, the effect of PTTG1 on trophoblast invasion was evaluated by microRNA (miRNA) mimic and inhibitor treatment. Trophoblast invasion was significantly reduced through decreased matrix metalloproteinase (MMP)-2 and MMP 9 expression when PTTG1 expression was inhibited by siPTTG1 (p < 0.05). Furthermore, knockdown of PTTG1 increased expression of integrin alpha 4 (ITGA4), ITGA5, and integrin beta 1 (ITGB1); otherwise, RhoA expression was significantly decreased (p < 0.05). Treatment of miRNA-186-5p mimic and inhibitor controlled trophoblast invasion ability by altering PTTG1 and MMP expression. PTTG1 can control trophoblast invasion ability via regulation of MMP expression through integrin/Rho-family signaling. In addition, PTTG1 expression and its function were regulated by miRNA-186-5p. These results help in understanding the mechanism through which PTTG1 regulates trophoblast invasion and thereby implantation and placental development. PMID- 26900963 TI - Intersubtype Reassortments of H5N1 Highly Pathogenic Avian Influenza Viruses Isolated from Quail. AB - H5N1 highly pathogenic avian influenza (HPAI) viruses are considered a threat to national animal industries, causing production losses and high mortality in domestic poultry. In recent years, quail has become a popular terrestrial poultry species raised for production of meat and eggs in Asia. In this study, to better understand the roles of quail in H5N1 viral evolution, two H5N1-positive samples, designated A/quail/Vietnam/CVVI-49/2010 (CVVI-49/2010) and A/quail/Vietnam/CVVI 50/2014 (CVVI-50/2014), were isolated from quail during H5N1 outbreaks in Vietnam, and their whole genome were analyzed. The phylogenetic analysis reveals new evolutionary variation in the worldwide H5N1 viruses. The quail HA genes were clustered into clades 1.1.1 (CVVI-49/2010) and clade 2.3.2.1c (CVVI-50/2014), which may have evolved from viruses circulating from chickens and/or ducks in Cambodia, mainland of China, Taiwan, Indonesia, and South Korea in recent years. Interestingly, the M2 gene of the CVVI-49/2010 strain contained amino acid substitutions at position 26L-I and 31S-N that are related to amantadine resistance. In particular, the CVVI-50/2014 strain revealed evidence of multiple intersubtype reassortment events between virus clades 2.3.2.1c, 2.3.2.1b, and 2.3.2.1a. Data from this study supports the possible role of quail as an important intermediate host in avian influenza virus evolution. Therefore, additional surveillance is needed to monitor these HPAI viruses both serologically and virologically in quail. PMID- 26900964 TI - gamma-AApeptides: Design, Structure, and Applications. AB - The development of sequence-specific peptidomimetics has led to a variety of fascinating discoveries in chemical biology. Many peptidomimetics can mimic primary, secondary, and even tertiary structure of peptides and proteins, and because of their unnatural backbones, they also possess significantly enhanced resistance to enzymatic hydrolysis, improved bioavailability, and chemodiversity. It is known that peptide nucleic acids (PNAs) are peptidic sequences developed for the mimicry of nucleic acids; however, their unique backbone as the molecular scaffold of peptidomimetics to mimic structure and function of bioactive peptides has not been investigated systematically. As such, we recently developed a new class of peptidomimetics, "gamma-AApeptides", based on the chiral gamma-PNA backbone. They are termed gamma-AApeptides because they are the oligomers of gamma-substituted-N-acylated-N-aminoethyl amino acids. Similar to other classes of peptidomimetics, gamma-AApeptides are also resistant to proteolytic degradation and possess the potential to enhance chemodiversity. Moreover, in our scientific journey on the exploration of this class of peptidomimetics, we have discovered some intriguing structures and functions of gamma-AApeptides. In this Account, we summarize the current development and application of gamma-AApeptides with biological potential. Briefly, both linear and cyclic (either through head to-tail or head-to-side-chain cyclization) gamma-AApeptides with diverse functional groups can be synthesized easily on the solid phase using the synthetic protocol we developed. gamma-AApeptides could mimic the primary structure of peptides, as they project the same number of side chains as peptides of the same lengths. For instance, they could mimic the Tat peptide to permeate cell membranes and bind to HIV RNA with high specificity and affinity. Certain gamma-AApeptides show similar activity to the RGD peptide and target integrin specifically on the cell surface. gamma-AApeptides with function akin to fMLF peptides are also identified. More importantly, we found that gamma-AApeptides can fold into discrete secondary structures, such as helical and beta-turn-like structures. Therefore, they could be rationally designed for a range of biological applications. For instance, gamma-AApeptides can mimic host-defense peptides and display potent and broad-spectrum activity toward a panel of drug resistant bacterial pathogens. Meanwhile, because of their stability against proteolysis and their chemodiversity, gamma-AApeptides are also amenable for combinatorial screening. We demonstrate that, through combinatorial selection, certain gamma-AApeptides are identified to inhibit Abeta40 peptide aggregation, suggesting their potential use as a molecular probe to intervene in Alzheimer's disease. In addition, a few gamma-AApeptides identified from the gamma-AApeptide library have been shown to bind to the DNA-binding domain of STAT3 and antagonize STAT3/DNA interactions. Our studies suggest that, with further studies and exploration on both structures and functions, gamma-AApeptides may emerge to be a new class of peptidomimetics that play an important role in chemical biology and biomedical sciences. PMID- 26900965 TI - Size-Resolved Identification, Characterization, and Quantification of Primary Biological Organic Aerosol at a European Rural Site. AB - Primary biological organic aerosols (PBOA) represent a major component of the coarse organic matter (OMCOARSE, aerodynamic diameter > 2.5 MUm). Although this fraction affects human health and the climate, its quantification and chemical characterization currently remain elusive. We present the first quantification of the entire PBOACOARSE mass and its main sources by analyzing size-segregated filter samples collected during the summer and winter at the rural site of Payerne (Switzerland), representing a continental Europe background environment. The size-segregated water-soluble OM was analyzed by a newly developed offline aerosol mass spectrometric technique (AMS). Collected spectra were analyzed by three-dimensional positive matrix factorization (3D-PMF), showing that PBOA represented the main OMCOARSE source during summer and its contribution to PM10 was comparable to that of secondary organic aerosol. We found substantial cellulose contributions to OMCOARSE, which in combination with gas chromatography mass spectrometry molecular markers quantification, underlined the predominance of plant debris. Quantitative polymerase chain reaction (qPCR) analysis instead revealed that the sum of bacterial and fungal spores mass represented only a minor OMCOARSE fraction (<0.1%). X-ray photoelectron spectroscopic (XPS) analysis of C and N binding energies throughout the size fractions revealed an organic N increase in the PM10 compared to PM1 consistent with AMS observations. PMID- 26900966 TI - Redescription of two little-known urostyloid ciliates, Anteholosticharandani (Groliere, 1975) Berger, 2003 and A. antecirrata Berger, 2006 (Ciliophora, Urostylida). AB - The morphology of two little-known urostyloid ciliates, Anteholosticha randani (Groliere, 1975) Berger, 2003 and A. antecirrataBerger, 2006, collected from freshwater biotopes in southern China, was studied based on live observations and protargol staining. Anteholosticha randani is characterized by its bipartite adoral zone and short, longitudinally aligned undulating membranes. One early stage of reorganization/morphogenesis, one early-middle stage of reorganization and one middle stage of morphogenesis are also reported. Anteholosticha antecirrata is characterized by its large body size in vivo (200-400 * 40-80 MUm), a row of buccal cirri and conspicuous, yellow-green cortical granules. Phylogenetic analyses based on SSU rDNA sequence data reveal that A. antecirrata may share a most recent common ancestor with Urostyla grandis and Bakuella granulifera, whereas A. randani branches independently and is sister to a large clade that includes Pseudourostyla, Pseudokeronopsis, Caudiholosticha and several species of Anteholosticha. PMID- 26900968 TI - Aluminum-induced changes in properties and fouling propensity of DOM solutions revealed by UV-vis absorbance spectral parameters. AB - The integration of pre-coagulation with ultrafiltration (UF) is expected to not only reduce membrane fouling but also improve natural organic matter (NOM) removal. However, it is difficult to determine the proper coagulant dosage for different water qualities. The objective of this study was to probe the potential of UV-vis spectroscopic analysis to reveal the coagulant-induced changes in the fouling potentials of dissolved organic matter (DOM) and to determine the optimal coagulant dosage. The Zeta potentials (ZPs) and average particle size of the four DOM solutions (Aldrich humic acid (AHA), AHA-sodium alginate (SA), AHA-bovine serum albumin (BSA) and AHA-dextran (DEX)) coagulated with aluminum chloride (AlCl3) were measured. Results showed that increasing the aluminum coagulant dosage induced the aggregation of DOM. Meanwhile, the addition of aluminum coagulant resulted in an increase in DSlope(325-375) (the slope of the log transformed absorbance spectra from 325 to 375 nm) and a decrease in S(275-295) (the slope of the log-transformed absorption coefficient from 275 to 295 nm) and SR (the ratio of Slope(275-295) and Slope(350-400)). The variations of these spectral parameters (i.e., DSlope(325-375), S(275-295) and SR) correlated well with the aluminum-caused changes in ZPs and average particle size. This implies that spectral parameters have the potential to indicate DOM aggregation. In addition, good correlations of spectral parameters and membrane fouling behaviors (i.e., unified membrane fouling index (UMFI)) suggest that the changes in DSlope(325-375), S(275-295) and SR were indicative of the aluminum-caused alterations of fouling potentials of all DOM solutions. Interestingly, the optimal dosage of aluminum (40 MUM for AHA, AHA-BSA, and AHA-DEX) was obtained based on the relation between spectral parameters and fouling behaviors. Overall, the spectroscopic analysis, particularly for the utilization of spectral parameters, provided a convenient approach for the exploration of combined coagulation and UF systems for DOM removal. PMID- 26900967 TI - Hippocampal functional connectivity and episodic memory in early childhood. AB - Episodic memory relies on a distributed network of brain regions, with the hippocampus playing a critical and irreplaceable role. Few studies have examined how changes in this network contribute to episodic memory development early in life. The present addressed this gap by examining relations between hippocampal functional connectivity and episodic memory in 4- and 6-year-old children (n=40). Results revealed similar hippocampal functional connectivity between age groups, which included lateral temporal regions, precuneus, and multiple parietal and prefrontal regions, and functional specialization along the longitudinal axis. Despite these similarities, developmental differences were also observed. Specifically, 3 (of 4) regions within the hippocampal memory network were positively associated with episodic memory in 6-year-old children, but negatively associated with episodic memory in 4-year-old children. In contrast, all 3 regions outside the hippocampal memory network were negatively associated with episodic memory in older children, but positively associated with episodic memory in younger children. These interactions are interpreted within an interactive specialization framework and suggest the hippocampus becomes functionally integrated with cortical regions that are part of the hippocampal memory network in adults and functionally segregated from regions unrelated to memory in adults, both of which are associated with age-related improvements in episodic memory ability. PMID- 26900969 TI - Examination of effects of Cu(II) and Cr(III) on Al(III) binding by dissolved organic matter using absorbance spectroscopy. AB - Effects of Cu(II) and Cr(III) ions on the binding of Al(III) onto Dissolved Organic Matter (DOM) exemplified by Suwannee River Humic Acid (SRHA) at pH 6.0 were quantified in this study using linear and log-transformed SRHA absorbance spectra acquired at varying Al(3+) concentrations and Cu(2+) or Cr(3+) levels. The competition between Al(3+) and Cu(2+)/Cr(3+) for the binding sites in DOM was ascertained by examining the intensity and shapes of the metal-specific differential spectra of DOM. The results indicated that the binding of Al(3+) onto SRHA is little influenced in the cases of in presence of 1.0 and 10.0 MUM background Cr(3+) and in presence of 1.0 MUM background Cu(2+), but it is significantly depressed in presence of 10.0 MUM Cu(2+). Changes of the spectral slope of the log-transformed absorbance spectra in the 350-400 nm wavelength range (S350-400) were unambiguously correlated with the total amount of DOM-bound metals. The concentrations of Me-DOM complexes were determined using the NICA Donnan Model. The results demonstrate that differential absorbance measurements provide quantitatively interpretable information concerning the nature and mechanisms of metal-DOM interactions and effects of metal cations competition on these processes. PMID- 26900970 TI - Strontium concentrations and isotope ratios in a forest-river system in the South Qinling Mts., China. AB - The concentrations of dissolved strontium (Sr) and isotope ratios ((87)Sr/(86)Sr) in rainwater, river water, and water from forest soil are measured to investigate the contributions of these sources to a river during base flow conditions in the relatively pristine South Qinling Mountains, China. Dissolved Sr concentrations and (87)Sr/(86)Sr ratios vary significantly between different water types (p < 0.01) suggesting that it is suitable for differentiating sources. Dissolved Sr is also positively correlated with most ions and a range of physicochemical parameters (p < 0.01 and p < 0.05 respectively) in water samples including Ca(2+), Mg(2+), EC, and TDS (p < 0.001) indicating their similarities in the drivers of biogeochemical processes and common origins. The correlations between Sr isotopes and Ca/Na, Ca/K, and 1000/Sr ratios suggest that three end-members of atmospheric inputs, carbonate and silicate weathering control the Sr water chemistry in the river water. Using the three-source mixing model, atmospheric inputs, carbonate, and silicate weathering contribute 74%, 20%, and 6% respectively to the dissolved Sr in the river water. This research has provided new insights into the contribution of sources of Sr to a river system in a mountainous catchment. PMID- 26900971 TI - Characterization and quantification of humic substances 2D-Fluorescence by usage of extended size exclusion chromatography. AB - In this article, two methods for in-depth analysis of humic substances fluorescence are presented. The first one allows the combined analysis of fluorescence excitation-emission matrix (EEM) with chromatography technique. The main issue is the coupling of size exclusion chromatography (SEC) with spectroscopy by the use of an absorption and a fluorescence spectrometer as additional detectors. These allow a detailed characterization of humic substances depending on their molecular size, concentration and optical properties. For the evaluation of the resulting complex data, a model based on non-negative matrix factorization, which is also presented in this article, was developed. From the results of the examined humic substances standards, the second method was developed. It allows the characterization and quantification of humic substances fluorescence of a natural water sample solely on the basis of an excitation emission matrix. The validation of the model is carried out within the framework of extensive analysis of real water samples. PMID- 26900972 TI - Transformation of Contaminant Candidate List (CCL3) compounds during ozonation and advanced oxidation processes in drinking water: Assessment of biological effects. AB - The removal of emerging contaminants during water treatment is a current issue and various technologies are being explored. These include UV- and ozone-based advanced oxidation processes (AOPs). In this study, AOPs were explored for their degradation capabilities of 25 chemical contaminants on the US Environmental Protection Agency's Contaminant Candidate List 3 (CCL3) in drinking water. Twenty three of these were found to be amenable to hydroxyl radical-based treatment, with second-order rate constants for their reactions with hydroxyl radicals (OH) in the range of 3-8 * 10(9) M(-1) s(-1). The development of biological activity of the contaminants, focusing on mutagenicity and estrogenicity, was followed in parallel with their degradation using the Ames and YES bioassays to detect potential changes in biological effects during oxidative treatment. The majority of treatment cases resulted in a loss of biological activity upon oxidation of the parent compounds without generation of any form of estrogenicity or mutagenicity. However, an increase in mutagenic activity was detected by oxidative transformation of the following CCL3 parent compounds: nitrobenzene (OH, UV photolysis), quinoline (OH, ozone), methamidophos (OH), N nitrosopyrolidine (OH), N-nitrosodi-n-propylamine (OH), aniline (UV photolysis), and N-nitrosodiphenylamine (UV photolysis). Only one case of formation of estrogenic activity was observed, namely, for the oxidation of quinoline by OH. Overall, this study provides fundamental and practical information on AOP-based treatment of specific compounds of concern and represents a framework for evaluating the performance of transformation-based treatment processes. PMID- 26900973 TI - Natural organic matter fouling behaviors on superwetting nanofiltration membranes. AB - Nanofiltration has been widely recognized as a promising technology for the removal of micro-molecular organic components from natural water. Natural organic matter (NOM), a very important precursor of disinfection by-products, is currently considered as the major cause of membrane fouling. It is necessary to develop a membrane with both high NOM rejection and anti-NOM fouling properties. In this study, both superhydrophilic and superhydrophobic nanofiltration membranes for NOM removal have been fabricated. The fouling behavior of NOM on superwetting nanofiltration membranes has been extensively investigated by using humic acid (HA) as the model foulant. The extended Derjaguin-Landau-Verwey Overbeek approach and nanoindentor scratch tests suggested that the superhydrophilic membrane had the strongest repulsion force to HA due to the highest positive total interaction energy (DeltaG(TOT)) value and the lowest critical load. Excitation emission matrix analyses of natural water also indicated that the superhydrophilic membrane showed resistance to fouling by hydrophobic substances and therefore high removal thereof. Conversely, the superhydrophobic membrane showed resistance to fouling by hydrophilic substances and therefore high removal capacity. Long-term operation suggested that the superhydrophilic membrane had high stability due to its anti-NOM fouling capacity. Based on the different anti-fouling properties of the studied superwetting membranes, a combination of superhydrophilic and superhydrophobic membranes was examined to further improve the removal of both hydrophobic and hydrophilic pollutants. With a combination of superhydrophilic and superhydrophobic membranes, the NOM rejection (RUV254) and DOC removal rates (RDOC) could be increased to 83.6% and 73.3%, respectively. PMID- 26900974 TI - Optimization of gravity-driven membrane (GDM) filtration process for seawater pretreatment. AB - Seawater pretreatment by gravity-driven membrane (GDM) filtration at 40 mbar has been investigated. In this system, a beneficial biofilm develops on the membrane that helps to stabilize flux. The effects of membrane type, prefiltration and system configuration on stable flux, biofilm layer properties and dissolved carbon removal were studied. The results show that the use of flat sheet PVDF membranes with pore sizes of 0.22 and 0.45 MUm in GDM filtration achieved higher stabilized permeate fluxes (7.3-8.4 L/m(2)h) than that of flat sheet PES 100 kD membranes and hollow fibre PVDF 0.1 MUm membranes. Pore constriction and cake filtration were identified as major membrane fouling mechanisms, but their relative contributions varied with filtration time for the various membranes. Compared to raw seawater, prefiltering of seawater with meshes at sizes of 10, 100 and 1000 MUm decreased the permeate flux, which was attributed to removal of beneficial eukaryotic populations. Optical coherence tomography (OCT) showed that the porosity of the biofouling layer was more significantly related with permeate flux development rather than its thickness and roughness. To increase the contact time between the biofilm and the dissolved organics, a hybrid biofilm-submerged GDM reactor was evaluated, which displayed significantly higher permeate fluxes than the submerged GDM reactor. Although integrating the biofilm reactor with the membrane system displayed better permeate quality than the GDM filtration cells, it could not effectively reduce dissolved organic substances in the seawater. This may be attributed to the decomposition/degradation of solid organic substances in the feed and carbon fixation by the biofilm. Further studies of the dynamic carbon balance are required. PMID- 26900975 TI - Growth, microcystin-production and proteomic responses of Microcystis aeruginosa under long-term exposure to amoxicillin. AB - Ecological risk of antibiotics due to the induction of antibiotic-resistant bacteria has been widely investigated, while studies on the hazard of antibiotic contaminants via the regulation of cyanobacteria were still limited. This study focused on the long-term action effect and mechanism of amoxicillin (a broadly used antibiotic) in Microcystis aeruginosa at environmentally relevant concentrations through 30 days of semi-continuous culture. Amoxicillin stimulated the photosynthesis activity and the production of microcystins, and interaction of differential proteins under amoxicillin exposure further manifested the close correlation between the two processes. D1 protein, ATP synthase subunits alpha and beta, enolase, triosephosphate isomerase and phosphoglycerate kinase were candidate target positions of amoxicillin in M. aeruginosa under long-term exposure. Amoxicillin affected the cellular biosynthesis process and the metabolism of carbohydrate and nucleoside phosphate according to the proteomic responses. Under exposure to amoxicillin, stimulated growth rate at the beginning phase and increased production and release of microcystins during the whole exposure period would lead to a higher contamination of M. aeruginosa cells and microcystins, indicating that amoxicillin was harmful to aquatic environments through the promotion of cyanobacterial bloom. PMID- 26900976 TI - Settleability and characteristics of ferrate(VI)-induced particles in advanced wastewater treatment. AB - Ferrate(VI) as an emerging water treatment agent has recently recaptured interests for advanced wastewater treatment. A large number of studies were published to report ferrate(VI)-driven oxidation for various water contaminants. In contrast, very few efforts were made to characterize ferrate(VI) resultant particles in water and wastewater. In this study, jar tests were performed to examine the settleability and characteristics of ferrate(VI)-induced iron oxide particles, particularly the non-settable fraction of these particles, after ferrate(VI) reduction in a biologically treated municipal wastewater. The particle settleability was evaluated through the measurement of turbidity and particulate iron concentration in the supernatant with the settling time. Results showed that a majority of ferrate(VI)-induced iron oxide aggregates remained suspended and caused an increased turbidity. For example, at a Fe(VI) dose of 5.0 mg/L and pH 7.50, 82% of the added iron remained in the supernatant and the turbidity was 8.97 NTU against the untreated sample turbidity (2.33 NTU) after 72 h settling. The poor settling property of these particles suggested that coagulation and flocculation did not perform well in the ferrate(VI) treatment. Particle size analysis and transmission electron microscopy (TEM) revealed that nano-scale particles were produced after ferrate(VI) decomposition, and gradually aggregated to form micro-scale larger particles in the secondary effluent. Zeta potentials of the non-settable ferrate(VI) resultant aggregates varied between 7.36 and -8.01 mV at pH 7.50 during the 72-h settling. The negative surface charges made the aggregates to be relatively stable in the wastewater matrix. PMID- 26900977 TI - The role of helper lipids in lipid nanoparticles (LNPs) designed for oligonucleotide delivery. AB - Lipid nanoparticles (LNPs) have shown promise as delivery vehicles for therapeutic oligonucleotides, including antisense oligos (ONs), siRNA, and microRNA mimics and inhibitors. In addition to a cationic lipid, LNPs are typically composed of helper lipids that contribute to their stability and delivery efficiency. Helper lipids with cone-shape geometry favoring the formation hexagonal II phase, such as dioleoylphosphatidylethanolamine (DOPE), can promote endosomal release of ONs. Meanwhile, cylindrical-shaped lipid phosphatidylcholine can provide greater bilayer stability, which is important for in vivo application of LNPs. Cholesterol is often included as a helper that improves intracellular delivery as well as LNP stability in vivo. Inclusion of a PEGylating lipid can enhance LNP colloidal stability in vitro and circulation time in vivo but may reduce uptake and inhibit endosomal release at the cellular level. This problem can be addressed by choosing reversible PEGylation in which the PEG moiety is gradually released in blood circulation. pH-sensitive anionic helper lipids, such as fatty acids and cholesteryl hemisuccinate (CHEMS), can trigger low-pH-induced changes in LNP surface charge and destabilization that can facilitate endosomal release of ONs. Generally speaking, there is no correlation between LNP activity in vitro and in vivo because of differences in factors limiting the efficiency of delivery. Designing LNPs requires the striking of a proper balance between the need for particle stability, long systemic circulation time, and the need for LNP destabilization inside the target cell to release the oligonucleotide cargo, which requires the proper selection of both the cationic and helper lipids. Customized design and empirical optimization is needed for specific applications. PMID- 26900978 TI - Tissue extraction technique at the time of laparoscopic myomectomy. PMID- 26900979 TI - Internalization and thermal susceptibility of Shiga toxin-producing Escherichia coli (STEC) in marinated beef products. AB - This study evaluated the internalization and cooking susceptibility of seven individual Escherichia coli (STEC) serogroups in surface-inoculated (10(5)log CFU/cm(2)) and vacuum tumbled marinated (30 or 60 min) bottom sirloin steaks. After storage for 14 days (0 to 2 degrees C), flaps were cooked to various endpoint temperatures (55, 60, 65, and 71 degrees C) for evaluation of pathogen survival by direct plating or rapid PCR based detection (BAX(r)). Direct plating of cooked samples yielded no enumerable plates. The data indicate varied internalization, translocation, and heat susceptibility patterns among serogroups. Using the rapid PCR based detection method O26, O103, and O111 were detected in flaps after cooking to 55 and 60 degrees C, while O157:H7 survived in flaps cooked to 60 and 65 degrees C. However, STEC O145 was the only serogroup that survived in all cooking temperatures. Serogroup O121 was not detected by plating or PCR in any cooked products. Intriguingly, STEC serogroups can be internalized during marination and the internalized pathogens vary in thermal susceptibility. PMID- 26900980 TI - Comparative toxicity and bioaccumulation of fenvalerate and esfenvalerate to earthworm Eisenia fetida. AB - More attention is being paid to the enantioselective toxicity of chiral pesticides. However, limited investigations have been done to assess the ecological risks of chiral pesticides to soil community. Fenvalerate (FV), an extensively used synthetic pyrethroid, is a typical chiral pesticide. The most insecticidally active enantiomer of FV, esfenvalerate (ESFV), also has been marketed and widely used. In this study, the toxicological sensitivity and bioaccumulation of FV and ESFV in earthworms were assessed. The results showed that FV was less toxic than ESFV, but more accumulated in earthworms. ESFV was at least 4 times more toxic to earthworms than FV according to the filter paper contact toxicity test and the artificial soil test. Enantiospecific induction in oxidative stress was observed in earthworms exposed to FV and ESFV. The bioaccumulation of FV and ESFV in earthworm tissues was also enantioselective, preferentially accumulating FV. The uptake of ESFV by earthworms was lower than that of FV, so that the biota to soil accumulation factor (BSAF) value of ESFV was lower than that of FV. Our findings suggest that the enantioselective toxicity and bioaccumulation of chiral pesticides should be considered for evaluating ecological risks of these compounds to non-target organisms. PMID- 26900981 TI - Carbamazepine degradation using a N-doped TiO2 coated photocatalytic membrane reactor: Influence of physical parameters. AB - Commercial alpha-Al2O3 photocatalytic membranes with a pore size of 200 and 800 nm were coated with N-doped TiO2 photocatalytic film using a sol-gel technique for concurrent bottom-up filtration and photocatalytic oxidation. X-ray diffraction confirmed that the deposited N-doped TiO2 films are in the form of anatase with 78-84% coverage of the membrane surface. The concentration of N found by X-ray photoelectron spectroscopy was in the range of 0.3-0.9 atomic percentage. Membrane permeability after coating decreased by 50% and 12% for the 200- and 800-nm membrane substrates, respectively. The impact of operational parameters on the photocatalytic activity (PCA) of the N-doped TiO2-coated membranes was examined in a laboratory flow cell based on degradation of the model micropollutant carbamazepine, using a solar simulator as the light source. The significant gap in degradation rate between flow through the membrane and flow on the surface of the membrane was attributed both to the hydraulic effect and in-pore PCA. N-doped TiO2-coated membranes showed enhanced activity for UV wavelengths, in addition to activity under visible light. Experiments of PCA under varying flow rates concluded that the process is in the mass-transfer control regime. Carbamazepine removal rate increased with temperature, despite the decrease in dissolved oxygen concentration. PMID- 26900982 TI - Carbon and nitrogen removal from glucose-glycine melanoidins solution as a model of distillery wastewater by catalytic wet air oxidation. AB - Sugarcane molasses distillery wastewater contains melanoidins, which are dark brown recalcitrant nitrogenous polymer compounds. Studies were carried out in batch mode to evaluate Pt and Ru supported catalysts in the Catalytic Wet Air Oxidation (CWAO) process of a synthetic melanoidins solution, prepared by stoichiometric reaction of glucose with glycine. The addition of a catalyst slightly improved TOC removal compared with the non-catalytic reaction, and especially promoted the conversion of ammonium produced from organically-bound nitrogen in melanoidins to molecular nitrogen and nitrate. The selectivity to N2 attained 89% in the presence of the Pt catalysts in the reaction conditions used (TOC=2200mgL(-1), TN=280mgL(-1), 0.5g catalyst loaded with 3% metal, 210 degrees C, 70bar total air pressure). To avoid leaching of the active metal by organically-bound nitrogen, the reaction was very efficiently performed in a two step reaction consisting in WAO to convert nitrogen into ammonium, before the introduction of a catalyst. PMID- 26900983 TI - Plasma Cholesterol-Lowering Activity of Lard Functionalized with Mushroom Extracts Is Independent of Niemann-Pick C1-like 1 Protein and ABC Sterol Transporter Gene Expression in Hypercholesterolemic Mice. AB - Interest in food matrices supplemented with mushrooms as hypocholesterolemic functional foods is increasing. This study was to (i) investigate the hypocholesterolemic activity of lard functionalized with mushroom extracts (LF) including fungal beta-glucans, water-soluble polysaccharides, or ergosterol and (ii) examine the LF influence on transcriptional mechanisms involved in cholesterol metabolism. mRNA levels of 17 cholesterol-related genes were evaluated in jejunum, cecum, and liver of high cholesterol-fed mice. The four tested LFs decreased plasma cholesterol by 22-42%, HDLc by 18-40%, and LDLc by 27 51%, and two of them increased mRNA levels of jejunal Npc1l1 and Abcg5 and hepatic Npc1l1. mRNA levels of other cholesterol-related genes were unchanged. These findings suggest that LF may have potential as a dietary supplement for counteracting diet-induced hypercholesterolemia and could be a source for the development of novel cholesterol-lowering functional foods. However, the cholesterol-lowering effect was unrelated to transcriptional changes, suggesting that post-transcriptional mechanisms could be involved. PMID- 26900984 TI - Meningococcal quadrivalent tetanus toxoid conjugate vaccine (MenACWY-TT, NimenrixTM): A review of its immunogenicity, safety, co-administration, and antibody persistence. AB - INTRODUCTION: Meningococcal disease is a major cause of morbidity and mortality worldwide with reported epidemics and outbreaks in different parts of the world. Despite the availability of antimicrobial therapy, challenges remain in early recognition and prevention of disease. Several vaccines have been developed to date aiming at preventing disease spread. DISCUSSION: MenACWY-TT (NimenrixTM) has been extensively studied for use in different age groups. Phase II and III randomized trials have demonstrated its immunogenicity when administered in children aged 1 year and older, adolescents and adults. It has an acceptable safety profile with minor adverse events comparable to other vaccines. Follow up studies have shown persistence of protective antibodies up to three years. MenACWY-TT was safely and effectively co-administered with different recommended vaccines. CONCLUSION: MenACWY-TT is a safe and immunogenic vaccine that can be used to protect against these four serogroups in individuals older than 1 year of age. PMID- 26900985 TI - Disseminated tumor cells and dormancy in prostate cancer metastasis. AB - It has been reported that disseminated tumor cells (DTCs) can be found in the majority of prostate cancer (PCa) patients, even at the time of primary treatment with no clinical evidence of metastatic disease. This suggests that these cells escaped the primary tumor early in the disease and exist in a dormant state in distant organs until they develop in some patients as overt metastases. Understanding the mechanisms by which cancer cells exit the primary tumor, survive the circulation, settle in a distant organ, and exist in a quiescent state is critical to understanding tumorigenesis, developing new prognostic assays, and designing new therapeutic modalities to prevent and treat clinical metastases. PMID- 26900986 TI - Endoscopic sleeve gastroplasty (the Apollo method): a new approach to obesity management. AB - BACKGROUND: Many obese patients cannot lose weight or reject conventional obesity management. Endoscopic sleeve gastroplasty (the Apollo method) is a pioneering coadjuvant, interventionist technique for the integral management of obesity. OBJECTIVES: The goals of this study were to report safety and efficacy results obtained at 6 months in patients undergoing endoscopic sleeve gastroplasty. MATERIAL AND METHODS: A prospective study was performed in 55 patients (13 males, 42 females) who were subjected to the Apollo technique; mean age was 43.5 years (range 25-60) and mean BMI was 37.7 kg/m2 (range 30-48). All received multidisciplinary follow-up for weight loss. Weight changes and presence of complications were assessed. Through the endoscope a triangular pattern suture is performed consisting of approximately 3-6 transmural (mucosa to serosa) stitches, using a cinch device to bring them nearer and form a plication. RESULTS: A total of 6-8 plications are used to provide a tubular or sleeve-shaped restriction to the gastric cavity. No major complications developed and patients were discharged at 24 hours following the procedure. Endoscopic and radiographic follow-up at 6 months post-procedure showed a well preserved tubular form to the stomach. After 6 months patients had lost 18.9 kg and 55.3% of excess weight. CONCLUSIONS: Endoscopic sleeve gastroplasty, together with dietary and psycho-behavioral changes, is a safe, effective technique in the coadjuvant management of obese patients. PMID- 26900987 TI - Transcription factor Fli-1 positively regulates lipopolysaccharide-induced interleukin-27 production in macrophages. AB - IL-27 is an important regulator of TLR4-activated innate immune. The mechanism by which IL-27 production is regulated in TLR4-activated innate immune remains largely unclear. Here we show that expression of transcription factor Fli-1 at protein level is increased in macrophages following LPS stimulation. Fli-1 overexpression increases LPS-activated IL-27 production in macrophages. Consistently, Fli-1 knockdown inhibits LPS-induced IL-27 production in macrophages. Chromatin immunoprecipitation (ChIP) assay reveals that Fli-1 binds the promoter of IL-27 p28 subunit. Further experiments manifest that Fli-1 binds the region between -250 and -150 bp upstream of the transcriptional start site of p28 gene and increases p28 gene promoter-controlled transcription. These results demonstrate that Fli-1 positively regulates IL-27 production in TLR4-activated immune response by promoting transcription of IL-27 p28 gene. PMID- 26900988 TI - Both Financial and Cognitive Decline Predict Clinical Progression in MCI. AB - We investigated the roles of financial/functional and cognitive abilities in predicting clinical progression in patients with mild cognitive impairment (MCI). In a longitudinal sample of 51 patients with consensus conference diagnosed MCI likely due to Alzheimer disease (AD), two-year change scores were calculated for a performance measure of functional ability, cognitive variables, and 3 outcome measures used to track progression in neurological disorders. We examined patterns of financial and cognitive decline across the 2-year study period, and used these data and the 3 outcome variables to construct discrete predictor models of clinical progression in MCI. We found that both financial skills and cognitive abilities declined over the 2-year study period, were significantly associated with clinical progression, and contributed unique variance to all 3 predictor models. The resulting models accounted for 40% to 75% of variance in clinical progression across outcome variables. Taken together, our results indicate that changes in both cognitive abilities and higher order functional skills appear integral to understanding clinical progression in MCI likely due to AD. Specifically, declines in financial skills contribute unique variance to measures commonly used to track progression in neurological disorders associated with aging, and thus represent an important functional marker of clinical progression in prodromal AD. PMID- 26900989 TI - Cytomegalovirus Immunoglobulin After Thoracic Transplantation: An Overview. AB - Cytomegalovirus (CMV) is a highly complex pathogen which, despite modern prophylactic regimens, continues to affect a high proportion of thoracic organ transplant recipients. The symptomatic manifestations of CMV infection are compounded by adverse indirect effects induced by the multiple immunomodulatory actions of CMV. These include a higher risk of acute rejection, cardiac allograft vasculopathy after heart transplantation, and potentially bronchiolitis obliterans syndrome in lung transplant recipients, with a greater propensity for opportunistic secondary infections. Prophylaxis for CMV using antiviral agents (typically oral valganciclovir or intravenous ganciclovir) is now almost universal, at least in high-risk transplants (D+/R-). Even with extended prophylactic regimens, however, challenges remain. The CMV events can still occur despite antiviral prophylaxis, including late-onset infection or recurrent disease, and patients with ganciclovir-resistant CMV infection or who are intolerant to antiviral therapy require alternative strategies. The CMV immunoglobulin (CMVIG) and antiviral agents have complementary modes of action. High-titer CMVIG preparations provide passive CMV-specific immunity but also exert complex immunomodulatory properties which augment the antiviral effect of antiviral agents and offer the potential to suppress the indirect effects of CMV infection. This supplement discusses the available data concerning the immunological and clinical effects of CMVIG after heart or lung transplantation. PMID- 26900990 TI - The Immunology of Posttransplant CMV Infection: Potential Effect of CMV Immunoglobulins on Distinct Components of the Immune Response to CMV. AB - The immune response to cytomegalovirus (CMV) infection is highly complex, including humoral, cellular, innate, and adaptive immune responses. Detection of CMV by the innate immune system triggers production of type I IFNs and inflammatory cytokines which initiate cellular and humoral responses that are critical during the early viremic phase of CMV infection. Sustained control of CMV infection is largely accounted for by cellular immunity, involving various T cell and B-cell subsets. In solid organ transplant patients, global suppression of innate and adaptive immunities by immunosuppressive agents limits immunological defense, including inhibition of natural killer cell activity with ongoing lowering of Ig levels and CMV-specific antibody titers. This is coupled with a short-term suppression of CMV-specific T cells, the extent and duration of which can predict risk of progression to CMV viremia. CMV immunoglobulin (CMVIG) preparations have the potential to exert immunomodulatory effects as well as providing passive immunization. Specific CMVIG antibodies and virus neutralization might be enhanced by modulation of dendritic cell activity and by a decrease in T-cell activation, effects which are of importance during the initial phase of infection. In summary, the role of CMVIG in reconstituting specific anti-CMV antibodies may be enhanced by some degree of modulation of the innate and adaptive immune responses, which could help to control some of the direct and indirect effects of CMV infection. PMID- 26900991 TI - Cytomegalovirus Hyper Immunoglobulin for CMV Prophylaxis in Thoracic Transplantation. AB - Cytomegalovirus (CMV) infection negatively influences both short- and long-term outcomes after cardiothoracic transplantation. In heart transplantation, registry analyses have shown that CMV immunoglobulin (CMVIG) with or without virostatic prophylaxis is associated with a significant reduction in mortality and graft loss versus no prophylaxis, particularly in high-risk donor (D)+/recipient (R)- transplants. Randomized comparative trials are lacking but retrospective data suggest that addition of CMVIG to antiviral prophylaxis may reduce rates of CMV related events after heart transplantation, including the incidence of acute rejection or chronic allograft vasculopathy. However, available data consistently indicate that when CMVIG is used, it should be administered with concomitant antiviral therapy, and that evidence concerning preemptive management with CMVIG is limited, but promising. In lung transplantation, CMVIG should again only be used with concomitant antiviral therapy. Retrospective studies have shown convincing evidence that addition of CMVIG to antiviral prophylaxis lowers CMV endpoints and mortality. The current balance of evidence suggests that CMVIG prophylaxis reduces the risk of bronchiolitis obliterans syndrome, but a controlled trial is awaited. Overall, the relatively limited current data set suggests that prophylaxis with CMVIG in combination with antiviral therapy appears effective in D+/R- heart transplant patients, whereas in lung transplantation, addition of CMVIG in recipients of a CMV-positive graft may offer an advantage in terms of CMV infection and disease. PMID- 26900993 TI - When to throw the switch: The adaptiveness of modifying emotion regulation strategies based on affective and physiological feedback. AB - Particular emotion regulation (ER) strategies are beneficial in certain contexts, but little is known about the adaptiveness of switching strategies after implementing an initial strategy. Research and theory on regulatory flexibility suggest that people switch strategies dynamically and that internal states provide feedback indicating when switches are appropriate. Frequent switching may predict positive outcomes among people who respond to this feedback. We investigated whether internal feedback (particularly corrugator activity, heart rate, or subjective negative intensity) guides people to switch to an optimal (i.e., distraction) but not nonoptimal (i.e., reappraisal) strategy for regulating strong emotion. We also tested whether switching frequency and responsiveness to internal feedback (RIF) together predict well-being. While attempting to regulate emotion elicited by unpleasant pictures, participants could switch to an optimal (Study 1; reappraisal-to-distraction order; N = 90) or nonoptimal (Study 2; distraction-to-reappraisal order; N = 95) strategy for high arousal emotion. A RIF score for each emotion measure indexed the relative strength of emotion during the initial phase for trials on which participants later switched strategies. As hypothesized, negative intensity, corrugator activity, and the magnitude of heart rate deceleration during this early phase were higher on switch than maintain trials in Study 1 only. Critically, in Study 1 only, greater switching frequency predicted higher and lower life satisfaction for participants with high and low corrugator RIF, respectively, even after controlling for reappraisal success. Individual differences in RIF may contribute to subjective well-being provided that the direction of strategy switching aligns well with regulatory preferences for high emotion. (PsycINFO Database Record PMID- 26900992 TI - CMV Immunoglobulins for the Treatment of CMV Infections in Thoracic Transplant Recipients. AB - Intravenous ganciclovir and, increasingly, oral valganciclovir are now considered the mainstay of treatment for cytomegalovirus (CMV) infection or CMV disease. Under certain circumstances, CMV immunoglobulin (CMVIG) may be an appropriate addition or, indeed, alternative. Data on monotherapy with CMVIG are limited, but encouraging, for example in cases of ganciclovir intolerance. In cases of recurrent CMV in thoracic transplant patients after a disease- and drug-free period, adjunctive CMVIG can be considered in patients with hypogammaglobulinemia. Antiviral-resistant CMV, which is more common among thoracic organ recipients than in other types of transplant, can be an indication for introduction of CMVIG, particularly in view of the toxicity associated with other options, such as foscarnet. Due to a lack of controlled trials, decision making is based on clinical experience. In the absence of a robust evidence base, it seems reasonable to consider the use of CMVIG to treat CMV in adult or pediatric thoracic transplant patients with ganciclovir-resistant infection, or in serious or complicated cases. The latter can potentially include (i) treatment of severe clinical manifestations, such as pneumonitis or eye complications; (ii) patients with a positive biopsy in end organs, such as the lung or stomach; (iii) symptomatic cases with rising polymerase chain reaction values (for example, higher than 5.0 log10) despite antiviral treatment; (iv) CMV disease or CMV infection or risk factors, such as CMV-IgG-negative serostatus; (vi) ganciclovir intolerance; (vii) patients with hypogammaglobulinemia. PMID- 26900994 TI - Towards lag phase of microbial populations at growth-limiting conditions: The role of the variability in the growth limits of individual cells. AB - The water activity (aw) growth limits of unheated and heat stressed Listeria monocytogenes individual cells were studied. The aw limits varied from 0.940 to 0.997 and 0.951 to 0.997 for unheated and heat stressed cells, respectively. Due to the above variability a decrease in aw results in the presence of a non growing fraction in the population leading to an additional pseudo-lag in population growth. In this case the total apparent lag of the population is the sum of the physiological lag of the growing cells (time required to adjust to the new environment) and the pseudo-lag. To investigate the effect of aw on the above lag components, the growth kinetics of L. monocytogenes on tryptone soy agar with aw adjusted to values ranging from 0.997 to 0.940 was monitored. The model of B&R was fitted to the data for the estimation of the apparent lag. In order to estimate the physiological lag of the growing fraction of the inoculum, the model was refitted to the growth data using as initial population level the number of cells that were able to grow (estimated from the number of colonies formed on the agar at the end of storage) and excluding the rest data during the lag. The results showed that for the unheated cells the apparent lag was almost identical to the physiological lag for aw values ranging from 0.997 to 0.970, as the majority of the cells in the initial population was able to grow in these conditions. As the aw decreased from 0.970 to 0.940 however, the number of cells in the population which were able to grow, decreased resulting to an increase in the pseudo-lag. The maximum value of pseudo-lag was 13.1h and it was observed at aw=0.940 where 10% of the total inoculated cells were able to grow. For heat stressed populations a pseudo-lag started to increase at higher aw conditions (0.982) compared to unheated cells. In contrast to the apparent lag, a linear relation between physiological lag and aw was observed for both unheated and heat stressed cells. PMID- 26900997 TI - Chronic restraint stress exacerbates nociception and inflammatory response induced by bee venom in rats: the role of the P2X7 receptors. AB - OBJECTIVE: Chronic restraint stress exacerbates pain and inflammation. The present study was designed to evaluate the effect of chronic restraint stress on inflammatory pain induced by subcutaneous injection of bee venom (BV). METHODS: First, we investigated: (1) the effect of two-week restraint stress with daily 2 or 8 h on the baseline paw withdrawal mechanical threshold (PWMT), paw withdrawal thermal latency (PWTL) and paw circumference (PC); (2) the effect of chronic stress on the spontaneous paw-flinching reflex (SPFR), decrease in PWM, PWTL and increase in PC of the injected paw induced by BV. RESULTS: The results showed that (1) chronic restraint decreased significantly the PWMT and inhibited significantly the increase in PC, but had no effect on PWTL, compared with control group; (2) chronic restraint enhanced significantly BV-induced SPFR and inflammatory swelling of the injected paw. In a second series of experiments, the role of P2X7 receptor (P2X7R) in the enhancement of BV-induced inflammatory pain produced by chronic restraint stress was determined. Systemic pretreatment with P2X7R antagonist completely reversed the decrease in PWMT produced by chronic restraint, inhibited significantly the enhancement of BV-induced inflammatory pain produced by chronic restraint stress. CONCLUSION: Taken together, our data indicate that chronic restraint stress-enhanced nociception and inflammation in the BV pain model, possibly involving the P2X7R. PMID- 26900998 TI - A hypothetical model of host-pathogen interaction of Streptococcus suis in the gastro-intestinal tract. AB - Streptococcus suis (SS) is a zoonotic pathogen that can cause systemic infection in pigs and humans. The ingestion of contaminated pig meat is a well-established risk factor for zoonotic S. suis disease. In our studies, we provide experimental evidence that S. suis is capable to translocate across the host gastro-intestinal tract (GIT) using in vivo and in vitro models. Hence, S. suis should be considered an emerging foodborne pathogen. In this addendum, we give an overview of the complex interactions between S. suis and host-intestinal mucosa which depends on the host origin, the serotype and genotype of S. suis, as well as the presence and expression of virulence factors involved in host-pathogen interaction. Finally, we propose a hypothetical model of S. suis interaction with the host-GIT taking in account differences in conditions between the porcine and human host. PMID- 26900999 TI - Cognitive grammar and aphasic discourse. AB - In cognitive grammar (CG), there is no clear division between language and other cognitive processes; all linguistic form is conceptually meaningful. In this pilot study, a CG approach was applied to investigate whether people with aphasia (PWA) have cognitive linguistic difficulty not predicted from traditional, componential models of aphasia. Narrative samples from 22 PWA (6 fluent, 16 non fluent) were compared with samples from 10 participants without aphasia. Between group differences were tested statistically. PWA had significant difficulty with temporal sequencing, suggesting problems that are not uniquely linguistic. For some, these problems were doubly dissociated with naming, used as a general measure of severity, which indicates that cognitive linguistic difficulties are not linked with more widespread brain damage. Further investigation may lead to a richer account of aphasia in line with contemporary linguistics and cognitive science approaches. PMID- 26901000 TI - Reviewer Assistance: Optimizing Comments for Major Revision and Reject Decisions. PMID- 26901001 TI - Imaging of Cystic Fibrosis and Pediatric Bronchiectasis. AB - 1. CT is superior to pulmonary function tests and chest radiography for the assessment and monitoring of cystic fibrosis (CF)-related lung disease and, also, of pediatric bronchiectasis not caused by CF (hereafter referred to as non-CF bronchiectasis). 2. Low-dose CT protocols that impart radiation doses similar to those used in chest radiography are feasible for the surveillance of patients with bronchiectasis. 3. Chest radiography is still most commonly used as the first-line imaging examination of choice for the assessment of acute complications related to bronchiectasis. 4. Pulmonary MRI, with or without the use of inhaled hyperpolarized gas, can be performed to obtain functional information, and, in dedicated centers, it may yield imaging results comparable to those obtained by CT. 5. Gastrointestinal and pancreaticobiliary manifestations of CF are observed with greater frequency in adults, because of increased life expectancy. PMID- 26901002 TI - Estimation of the Number of Compartments Associated With the Apparent Diffusion Coefficient in MRI: The Theoretical and Experimental Investigations. AB - OBJECTIVE: The goal of the present study was to estimate the number of compartments and the mean apparent diffusion coefficient (ADC) value with the use of the DWI signal curve. MATERIALS AND METHODS: A useful new mathematic model that includes internal correlation among subcompartments with a distinct number of compartments was proposed. The DWI signal was simulated to estimate the approximate association between the number of subcompartments and the molecular density, with density corresponding to the ratio of the ADC values of the compartments, as determined using the Monte Carlo method. RESULTS: Various factors, such as energy depletion, temperature, intracellular water accumulation, changes in the tortuosity of the extracellular diffusion paths, and changes in cell membrane permeability, have all been implicated as factors contributing to changes in the ADC of water (ADCw); therefore, one may consider them as pseudocompartments in the new model proposed in this study. The lower the coefficient is, the lower the contribution of the compartment to the net signal will be. The results of the simulation indicate that when the number of compartments increases, the signal will become significantly lower, because the gradient factor (i.e., the b value) will increase. In other words, the signal curve is approximately linear at all b values when the number of compartments in which the tissues have been severely damaged is low; however, when the number of compartments is high, the curve will become constant at high b values, and the perfusion parameters will prevail on the diffusion parameters at low b values. Therefore, normal tissues will be investigated when the number of compartments and the ADC values are high and the b values are low, whereas damaged tissues will be evaluated when the number of compartments and the ADC values are low and the b values are high. CONCLUSION: The present study investigates damaged tissues at high b values for which the effect of eddy currents will also be compensated. These b values will probably be used in functional MRI. PMID- 26901003 TI - The Value of a Multidisciplinary Approach to the Diagnosis of Usual Interstitial Pneumonitis and Idiopathic Pulmonary Fibrosis: Radiology, Pathology, and Clinical Correlation. AB - OBJECTIVE: Multidisciplinary discussion is essential in establishing the diagnosis of idiopathic pulmonary fibrosis (IPF) and in determining prognosis. CONCLUSION: The CT and histopathologic correlate for IPF is usual interstitial pneumonitis (UIP). If a high-confidence diagnosis of UIP is made on CT, IPF is almost always the diagnosis, obviating lung biopsy. If a confident diagnosis of UIP cannot be made on CT, further assessment with lung biopsy and multidisciplinary discussion are often necessary to achieve a confident final diagnosis. PMID- 26901004 TI - Influence of Respiratory Position on Contrast Attenuation in Pulmonary CT Angiography: A Prospective Randomized Clinical Trial. AB - OBJECTIVE: The purpose of this study was to prospectively compare the effect of inspiration and resting expiratory position on contrast enhancement in pulmonary CT angiography (CTA) in a randomized clinical trial. SUBJECTS AND METHODS: In accordance with a power analysis performed before the study, we included 28 consecutive patients referred for evaluation of suspected pulmonary embolism in this prospective study. Patients were randomly assigned to perform either inspiration (n = 14; six men, eight women; mean age [SD], 38.1 +/- 9.8 years) or resting expiratory position (n = 14; six men, eight women; mean age: 42.1 +/- 9.2 years). All patients were scanned in a standardized supine position and scanning parameters were kept constant. Contrast medium was injected automatically with bolus tracking. Objective pulmonary vessel attenuation was quantified with digital measurement. Results were analyzed by using the unpaired t test and chi square test. RESULTS: Patients in the resting expiratory position showed significantly higher contrast attenuation than those who performed inspiration (302.9 +/- 11.9 HU vs 221.5 +/- 20.9 HU; p < 0.01). There were no significant differences in applied total volume of contrast agent (76.8 +/- 1.9 mL vs 75.7 +/ 1.6 mL; p = 0.6765), total volume including normal saline bolus (116.8 mL +/- 2.8 mL vs 121.8 mL +/- 2.3 mL; p = 0.1724) or flow rate (3.1 mL/s +/- 0.1 mL/s vs 3.2 mL/s +/- 0.1 mL/s). CONCLUSION: Pulmonary CTA should be performed in the resting expiratory position, and patients should be instructed to avoid inspiration to achieve the highest possible attenuation in the pulmonary arteries. PMID- 26901005 TI - CT in Idiopathic Pulmonary Fibrosis: Diagnosis and Beyond. AB - OBJECTIVE: This review focuses on recent idiopathic pulmonary fibrosis guidelines with regard to CT-based diagnosis, the limitations and potential sources of diagnostic error in their clinical application, and proposals for future guideline modification and improvement. The review also addresses the use of CT in disease monitoring, prognostic assessment, and therapeutic clinical trials. CONCLUSION: Ongoing research and clinical experience highlight the need for updating existing guidelines frequently. PMID- 26901006 TI - A Systematic Review and Meta-Analysis of Diagnostic Performance of MRI for Evaluation of Acute Appendicitis. AB - OBJECTIVE: A meta-analysis was performed to determine the accuracy of MRI in the diagnosis of acute appendicitis in the general population and in subsets of pregnant patients and children. MATERIALS AND METHODS: A systematic search of the PubMed and EMBASE databases for articles published through the end of October 2014 was performed to identify studies that used MRI to evaluate patients suspected of having acute appendicitis. Pooled data for sensitivity, specificity, and positive and negative predictive values were calculated. RESULTS: A total of 30 studies that comprised 2665 patients were reviewed. The sensitivity and specificity of MRI for the diagnosis of acute appendicitis are 96% (95% CI, 95 97%) and 96% (95% CI, 95-97%), respectively. In a subgroup of studies that focused solely on pregnant patients, the sensitivity and specificity of MRI were 94% (95% CI, 87-98%) and 97% (95% CI, 96-98%), respectively, whereas in studies that focused on children, sensitivity and specificity were found to be 96% (95% CI, 95-97%) and 96% (95% CI, 94-98%), respectively. CONCLUSION: MRI has a high accuracy for the diagnosis of acute appendicitis, for a wide range of patients, and may be acceptable for use as a first-line diagnostic test. PMID- 26901007 TI - Minimally Required Iodine Dose for the Detection of Hypervascular Hepatocellular Carcinoma on 80-kVp CT. AB - OBJECTIVE: The objective of our study was to determine the iodine dose per unit of body weight (BW) or body surface area (BSA) that is minimally required to detect hypervascular hepatocellular carcinoma (HCC) on 80-kVp CT. SUBJECTS AND METHODS: One hundred eleven patients (78 men and 33 women; mean age, 68 years; age range, 43-85 years) with chronic hepatitis were randomized into three groups with different iodine loads (0.5, 0.4, and 0.3 g I/kg BW) and underwent contrast enhanced CT at 80 kVp. Enhancement of the liver and of hypervascular HCCs was quantitatively and qualitatively assessed on hepatic arterial, portal venous, and equilibrium phase images and compared between the groups. Values for iodine dose per unit of BSA (g I/m(2)) were also computed and analyzed. RESULTS: No significant differences in the contrast-to-noise ratio (CNR) of hypervascular HCCs in any phase were found between the groups (p = 0.34-0.99). In the portal venous phase, the mean increase in hepatic contrast enhancement (DeltaHU) of the 0.5 g I/kg group (80.3 HU) was higher than those of the 0.4 g I/kg (63.4 HU) and 0.3 g I/kg (53.3 HU) groups (p < 0.001). Linear correlation equations for the increase in hepatic contrast enhancement were as follows: DeltaHU = 5.9 + 150.0 * IL(BW) (r = 0.69, p < 0.001), where IL(BW) is the iodine load per unit of BW (g I/kg), and DeltaHU = 13.0 + 3.68 * IL(BSA) (r = 0.66, p < 0.001), where IL(BSA) is the iodine load pre unit of BSA (g I/m(2)). CONCLUSION: The minimal iodine dose required to achieve a tumor-to-liver CNR that is acceptable for the detection of hypervascular HCCs on 80-kVp CT was 0.3 g I/kg BW or 11.0 g I/m(2) BSA. PMID- 26901008 TI - Presurgical Evaluation of Pancreatic Cancer: A Comprehensive Imaging Comparison of CT Versus MRI. AB - OBJECTIVE: The purpose of this study was to compare comprehensive CT and MRI in the presurgical evaluation of pancreatic cancer. MATERIALS AND METHODS: Thirty eight patients with pathologically proven pancreatic cancer were included in a retrospective study. CT with negative-contrast CT cholangiopancreatography and CT angiography (CTA) (CT image set) versus MRI with MRCP and MR angiography (MRI image set) were analyzed independently by two reviewers for tumor detection, extension, metastasis, vascular invasion, and resectability. These results were compared with the surgical and pathologic findings. RESULTS: The rate of detection of tumors was higher with MRI than with CT but not significantly so (reviewer 1, p = 1.000; reviewer 2, p = 0.500). In the evaluation of vessel involvement, nodal status, and resectability, although CT had higher ROC AUC values than did MRI (reviewer 1, 0.913 vs 0.858, 0.613 vs 0.503, and 0.866 vs 0.774; reviewer 2, 0.879 vs 0.849, 0.640 vs 0.583, and 0.830 vs 0.815), the differences were not statistically significant (p = 0.189 vs 0.494, 0.328 vs 0.244, and 0.193 vs 0.813 for reviewers 1 and 2). In the evaluation of tumor extension and organ metastases in the 38 patients, correct diagnosis of one of two liver metastases was achieved with both image sets, one case of omental and one case of peritoneal seeding were underestimated, and one case of stomach invasion was overestimated. CONCLUSION: MRI and CT had similar performance in the presurgical evaluation of pancreatic cancer. PMID- 26901009 TI - Threshold for Enhancement in Treated Hepatocellular Carcinoma on MDCT: Effect on Necrosis Quantification. AB - OBJECTIVE: The objective of our study was to determine whether the conventionally used enhancement threshold of 10 HU for assessing tumor viability in treated hepatocellular carcinoma (HCC) lesions is valid. MATERIALS AND METHODS: To distinguish pseudoenhancement from enhancement in a tumor, we used an in vivo model: The attenuation of 54 hepatic cysts during the unenhanced and portal venous phases of MDCT, similar to what may be observed in HCC with central necrosis, was used to determine the threshold for pseudoenhancement. To validate this model, we compared the attenuation value of liver parenchyma in this cohort with that of 22 HCCs during the late arterial phase of enhancement. We tested the effect of this pseudoenhancement on quantifying necrosis in HCC compared with the conventionally used threshold of 10 HU. RESULTS: Values of enhancing HCC tissue on arterial phase MDCT (mean, 121.3 HU) were comparable with normal liver parenchyma on venous phase MDCT (117.3 HU) (p = 0.27). The threshold of 17.1 HU was the best threshold for the detection of pseudoenhancement in cysts (99% accuracy, 100% sensitivity, and 98% specificity). When this threshold was used instead of the conventional threshold of 10 HU, the mean necrosis proportion of treated HCC increased from 34.0% to 42.6% and the mean viable tumor proportion decreased from 66.0% to 57.4%. The quantification of viable HCC tissue based on 10 HU and the quantification of viable HCC tissue based on 17.1 HU were found to be significantly different (p < 0.0001). CONCLUSION: The threshold of 17.1 HU may be the appropriate cutoff for nonenhancement in a necrotic HCC. Use of this threshold may potentially affect how response to therapy is quantified and categorized. PMID- 26901011 TI - Enhancement Threshold of Small (< 4 cm) Solid Renal Masses on CT. AB - OBJECTIVE: The objective of our study was to determine whether small (< 4 cm) solid renal cell carcinomas (RCCs) enhance on CT below the published enhancement thresholds. MATERIALS AND METHODS: For this retrospective study, we reviewed CT examinations of patients with pathologically characterized small solid renal masses. Patients with lipid-rich angiomyolipomas were excluded. The study included consecutive patients who had pathologically characterized small (< 4 cm) renal masses and had undergone CT during the un-enhanced phase and nephrographic phase (NP). Most CT examinations also included imaging during the corticomedullary phase (CMP); four patients did not have CMP images. The CT examinations were performed on a 64-MDCT scanner. Similar-sized ROIs were placed on each lesion on unenhanced and enhanced images and enhancement (in Hounsfield units) was calculated. Masses were considered solid with a threshold enhancement greater than either 15 or 20 HU. RESULTS: There were 137 masses in 137 patients, 90 men and 47 women (age range, 21-91 years; median age, 65 years). The renal masses were 1.0-3.9 cm (median, 2.4 cm). Of the 137 masses, 117 (85.4%) were malignant and 20 (14.6%) were benign. One malignant mass and three benign masses did not have CMP images. Twenty of the 116 (17.2%) renal cell carcinomas (RCCs) did not reach the 15-HU threshold enhancement on CMP images, nine of 117 masses (7.7%) did not reach the 15-HU enhancement threshold on NP images, and four of 117 masses (3.4%) did not reach the 15-HU enhancement threshold on both CMP and NP images. The numbers of masses that did not reach the 20-HU enhancement threshold were 24 of 116 masses (20.7%) on CMP images, 14 of 117 masses (11.9%) on NP images, and 11 of 117 masses (9.4%) on both CMP and NP images. Depending on the phase or enhancement threshold, 13.6-59.1% of papillary RCCs did not reach the enhancement threshold. CONCLUSION: A minority of small RCCs do not reach either a 15- or 20-HU enhancement threshold and might be misinterpreted as a hyperattenuating cyst. Most RCCs below these enhancement thresholds are papillary RCC. PMID- 26901010 TI - Effect of Stereotactic Body Radiotherapy on the Growth Kinetics and Enhancement Pattern of Primary Renal Tumors. AB - OBJECTIVE: The objective of our study was to assess the growth rate and enhancement of renal masses before and after treatment with stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS: This retrospective study included all patients with renal masses who underwent SBRT during a 5-year period. Orthogonal measurements of renal masses were obtained on pre- and posttreatment CT or MRI. Pre- and posttreatment growth rates were compared for renal mass diameter and volume using the t test. Pre- and posttreatment tumor enhancement values were compared for tumors that underwent multiphasic contrast-enhanced MRI. RESULTS: Forty patients underwent SBRT for the treatment of 41 renal tumors: clear cell renal cell carcinomas (RCCs) (n = 16), papillary RCCs (n = 6), oncocytic neoplasms (n = 8), unclassified RCCs (n = 2), urothelial carcinoma (n = 1), and no pathologic diagnosis (n = 8). The mean maximum tumor diameter before treatment was 3.9 cm (range, 1.6-8.3 cm). Three hundred thirty-eight pre- and posttreatment imaging studies were analyzed: 214 MRI studies and 124 CT studies. The mean pre- and posttreatment lengths of observation were 416 days (range, 2-1800 days) and 561 days (83-1366 days), respectively. The mean pretreatment tumor growth rate of 0.68 cm/y decreased to -0.37 cm/y post treatment (p < 0.0001), and the mean tumor volume growth rate of 21.2 cm(3)/y before treatment decreased to -5.35 cm(3)/y after treatment (p = 0.002). Local control-defined as less than 5 mm of growth was achieved in 38 of 41 (92.7%) tumors. The Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 showed progression in one tumor (2.4%), stability in 31 tumors (75.6%), partial response in eight tumors (19.5%), and complete response in one tumor (2.4%). No statistically significant change in tumor enhancement was shown (mean follow-up, 142 days; range, 7-581 days). CONCLUSION: Renal tumors treated with SBRT show statistically significant reductions in growth rate and tumor size after treatment but do not show statistically significant differences in enhancement in the initial (mean, 142 days) posttreatment period. PMID- 26901013 TI - Use of MRI in Differentiation of Papillary Renal Cell Carcinoma Subtypes: Qualitative and Quantitative Analysis. AB - OBJECTIVE: The purpose of this study was to determine whether qualitative and quantitative MRI feature analysis is useful for differentiating type 1 from type 2 papillary renal cell carcinoma (PRCC). MATERIALS AND METHODS: This retrospective study included 21 type 1 and 17 type 2 PRCCs evaluated with preoperative MRI. Two radiologists independently evaluated various qualitative features, including signal intensity, heterogeneity, and margin. For the quantitative analysis, a radiology fellow and a medical student independently drew 3D volumes of interest over the entire tumor on T2-weighted HASTE images, apparent diffusion coefficient parametric maps, and nephrographic phase contrast enhanced MR images to derive first-order texture metrics. Qualitative and quantitative features were compared between the groups. RESULTS: For both readers, qualitative features with greater frequency in type 2 PRCC included heterogeneous enhancement, indistinct margin, and T2 heterogeneity (all, p < 0.035). Indistinct margins and heterogeneous enhancement were independent predictors (AUC, 0.822). Quantitative analysis revealed that apparent diffusion coefficient, HASTE, and contrast-enhanced entropy were greater in type 2 PRCC (p < 0.05; AUC, 0.682-0.716). A combined quantitative and qualitative model had an AUC of 0.859. Qualitative features within the model had interreader concordance of 84-95%, and the quantitative data had intraclass coefficients of 0.873-0.961. CONCLUSION: Qualitative and quantitative features can help discriminate between type 1 and type 2 PRCC. Quantitative analysis may capture useful information that complements the qualitative appearance while benefiting from high interobserver agreement. PMID- 26901012 TI - Quantitative Multiparametric MRI Features and PTEN Expression of Peripheral Zone Prostate Cancer: A Pilot Study. AB - OBJECTIVE: The objective of our study was to investigate associations between quantitative image features of multiparametric MRI of the prostate and PTEN expression of peripheral zone prostate cancer. MATERIALS AND METHODS: A total of 45 peripheral zone cancer foci from 30 patients who had undergone multiparametric prostate MRI before prostatectomy were identified by a genitourinary pathologist and a radiologist who reviewed histologic findings and MR images. Histologic sections of cancer foci underwent immunohistochemical analysis and were scored according to the percentage of tumor-positive cells expressing PTEN as negative (0-20%), mixed (20-80%), or positive (80-100%). Average and 10th percentile apparent diffusion coefficient (ADC) values, skewness of T2-weighted signal intensity histogram, and quantitative perfusion parameters (i.e., forward volume transfer constant [K(trans)], extravascular extracellular volume fraction [ve], and reverse reflux rate constant between the extracellular space and plasma [k(ep)]) from the Tofts model were calculated for each cancer focus. Associations between the quantitative image features and PTEN expression were analyzed with the Spearman rank correlation coefficient (r). RESULTS: Analysis of the 45 cancer foci revealed that 21 (47%) were PTEN-positive, 12 (27%) were PTEN-negative, and 12 (27%) were mixed. There was a weak but significant negative correlation between Gleason score and PTEN expression (r = -0.30, p = 0.04) and between k(ep) and PTEN expression (r = -0.35, p = 0.02). There was no significant correlation between other multiparametric MRI features and PTEN expression. CONCLUSION: This preliminary study of radiogenomics of peripheral zone prostate cancer revealed weak-but significant-associations between the quantitative dynamic contrast enhanced MRI feature k(ep) and Gleason score with PTEN expression. These findings warrant further investigation and validation with the aim of using multiparametric MRI to improve risk assessment of patients with prostate cancer. PMID- 26901014 TI - Impact of Communication Errors in Radiology on Patient Care, Customer Satisfaction, and Work-Flow Efficiency. AB - OBJECTIVE: The purpose of this study is to analyze the impact of communication errors on patient care, customer satisfaction, and work-flow efficiency and to identify opportunities for quality improvement. MATERIALS AND METHODS: We performed a search of our quality assurance database for communication errors submitted from August 1, 2004, through December 31, 2014. Cases were analyzed regarding the step in the imaging process at which the error occurred (i.e., ordering, scheduling, performance of examination, study interpretation, or result communication). The impact on patient care was graded on a 5-point scale from none (0) to catastrophic (4). The severity of impact between errors in result communication and those that occurred at all other steps was compared. Error evaluation was performed independently by two board-certified radiologists. Statistical analysis was performed using the chi-square test and kappa statistics. RESULTS: Three hundred eighty of 422 cases were included in the study. One hundred ninety-nine of the 380 communication errors (52.4%) occurred at steps other than result communication, including ordering (13.9%; n = 53), scheduling (4.7%; n = 18), performance of examination (30.0%; n = 114), and study interpretation (3.7%; n = 14). Result communication was the single most common step, accounting for 47.6% (181/380) of errors. There was no statistically significant difference in impact severity between errors that occurred during result communication and those that occurred at other times (p = 0.29). In 37.9% of cases (144/380), there was an impact on patient care, including 21 minor impacts (5.5%; result communication, n = 13; all other steps, n = 8), 34 moderate impacts (8.9%; result communication, n = 12; all other steps, n = 22), and 89 major impacts (23.4%; result communication, n = 45; all other steps, n = 44). In 62.1% (236/380) of cases, no impact was noted, but 52.6% (200/380) of cases had the potential for an impact. CONCLUSION: Among 380 communication errors in a radiology department, 37.9% had a direct impact on patient care, with an additional 52.6% having a potential impact. Most communication errors (52.4%) occurred at steps other than result communication, with similar severity of impact. PMID- 26901015 TI - Dual-Energy CT-Based Differentiation of Benign Posttreatment Changes From Primary or Recurrent Malignancy of the Head and Neck: Comparison of Spectral Hounsfield Units at 40 and 70 keV and Iodine Concentration. AB - OBJECTIVE: The goals of our study were to evaluate dual-energy CT (DECT) differences between benign posttreatment changes and primary or recurrent head and neck malignancies in terms of spectral Hounsfield units for virtual monochromatic series at 40 keV and iodine concentration and compare their utility with that of spectral Hounsfield units at 70 keV. MATERIALS AND METHODS: A retrospective review of patients with a history of head and neck malignancy evaluated with DECT of the neck from November 2012 through December 2014 revealed 16 patients with benign posttreatment changes and 24 with malignancies (17 primary tumors and seven recurrent tumors). One reader placed ROIs within benign posttreatment changes or malignant tumors in each patient to generate spectral Hounsfield units at 40 keV, iodine concentration, and spectral Hounsfield units at 70 keV, and the Wilcoxon rank sum test was used to evaluate the differences between the two cohorts. ROC curves were also generated, and AUC and partial AUC were calculated at the three following specificities: 75%, 80%, and 90%. RESULTS: Malignant tissues were significantly different from benign posttreatment changes in spectral Hounsfield units at 40 keV (p < 0.0001), iodine concentration (p < 0.0001), and spectral Hounsfield units at 70 keV (p = 0.0001). The AUCs were 0.949, 0.943, and 0.858 for spectral Hounsfield units at 40 keV, iodine concentration, and spectral Hounsfield units at 70 keV, respectively. Both spectral Hounsfield units at 40 keV and iodine concentration had statistically higher partial AUCs than spectral Hounsfield units at 70 keV at 90% specificity (p = 0.0133 and 0.0063, respectively) but were not significantly different from each other. CONCLUSION: DECT-derived spectral Hounsfield units at 40 keV and iodine concentration may be superior to spectral Hounsfield units at 70 keV, which is similar to MDCT, in differentiating benign posttreatment changes from primary or recurrent head and neck malignancies. PMID- 26901016 TI - Radiographic Appearance of Transforaminal Lumbar Interbody Fusion Performed With and Without Recombinant Human Morphogenetic Protein-2. AB - OBJECTIVE: The purpose of this study is to determine whether recombinant human morphogenetic protein-2 (rhBMP-2) alters the findings on routine radiographs performed after transforaminal lumbar interbody fusion (TLIF). MATERIALS AND METHODS: A retrospective review of 256 TLIF procedures in 200 patients was performed over a 4-year period. The rhBMP-2 group included 204 TLIFs in 160 patients, and the control group included 52 TLIFs in 40 patients. Two musculoskeletal radiologists reviewed the postoperative radiographs for endplate resorption, resorption resolution, new bone formation, bridging bone, and allograft migration. Statistical analysis was performed using logistic regression. RESULTS: The median age was 53 years in the rhBMP-2 group and 54 years in the control group (p = 0.182). The groups were similar with regard to sex (p = 0.517), single or multilevel TLIF (p = 0.921), specific TLIF levels (p = 0.53), and median radiographic follow-up (373 vs 366 days; p = 0.34). Findings that were more common in the rhBMP-2 group than in the control group included endplate resorption (38% [78/204] vs 12% [6/52]; odds ratio [OR], 4.67; 95% CI, 1.99-12.54; p < 0.001), resorption resolution (59% [46/78] vs 0% [0/6]; OR, 8.09; 95% CI, 1.41 to infinity; p = 0.022), new bone formation (84% [171/204] vs 67% [35/52]; OR, 2.51; 95% CI, 1.24-4.99; p = 0.011), bridging bone (55% [112/204] vs 31% [16/52]; OR, 2.73; 95% CI, 1.43-5.34; p = 0.002), and allograft migration (17% [35/204] vs 2% [1/52]; OR, 6.30; 95% CI, 0.91-151.41; p = 0.065). CONCLUSION: A statistically significant higher frequency of endplate resorption, new bone formation, and bone bridging is present in TLIF augmented by rhBMP-2 compared with TLIF performed without rhBMP-2. Endplate resorption resolves without treatment in most cases after rhBMP-2 use. PMID- 26901017 TI - MRI of the Trigeminal Nerve in Patients With Trigeminal Neuralgia Secondary to Vascular Compression. AB - OBJECTIVE: Trigeminal neuralgia is a debilitating facial pain disorder, frequently caused by vascular compression of the trigeminal nerve. Vascular compression that results in trigeminal neuralgia occurs along the cisternal segment of the nerve. CONCLUSION: Imaging combined with clinical information is critical to correctly identify patients who are candidates for microvascular decompression. The purpose of this article is to review trigeminal nerve anatomy and to provide strategies for radiologists to recognize important MRI findings in patients with trigeminal neuralgia. PMID- 26901018 TI - Investigation of Acoustic Structure Quantification in the Diagnosis of Thyroiditis. AB - OBJECTIVE: The objective of this study was to evaluate the ability of acoustic structure quantification (ASQ) to diagnose thyroiditis. MATERIALS AND METHODS: The echogenicity of 439 thyroid lobes, as determined using ASQ, was quantified and analyzed retrospectively. Thyroiditis was categorized into five subgroups. The results were presented in a modified chi-square histogram as the mode, average, ratio, blue mode, and blue average. We determined the cutoff values of ASQ from ROC analysis to detect and differentiate thyroiditis from a normal thyroid gland. We obtained data on the sensitivity and specificity of the cutoff values to distinguish between euthyroid patients with thyroiditis and patients with a normal thyroid gland. RESULTS: The mean ASQ values for patients with thyroiditis were statistically significantly greater than those for patients with a normal thyroid gland (p < 0.001). The AUCs were as follows: 0.93 for the ratio, 0.91 for the average, 0.90 for the blue average, 0.87 for the mode, and 0.87 for the blue mode. For the diagnosis of thyroiditis, the cutoff values were greater than 0.27 for the ratio, greater than 116.7 for the mean, and greater than 130.7 for the blue average. The sensitivities and specificities were as follows: 84.0% and 96.6% for the ratio, 85.3% and 83.0%, for the average, and 79.1% and 93.2% for the blue average, respectively. The ASQ parameters were successful in distinguishing patients with thyroiditis from patients with a normal thyroid gland, with likelihood ratios of 24.7 for the ratio, 5.0 for the average, and 11.6 for the blue average. With the use of the aforementioned cutoff values, the sensitivities and specificities for distinguishing between patients with thyroiditis and euthyroid patients without thyroiditis were 77.05% and 94.92% for the ratio, 85.25% and 82.20% for the average, and 77.05% and 92.37% for the blue average, respectively. CONCLUSION: ASQ can provide objective and quantitative analysis of thyroid echogenicity. ASQ parameters were successful in distinguishing between patients with thyroiditis and individuals without thyroiditis, with likelihood ratios of 24.7 for the ratio, 5.0 for the average, and 11.6 for the blue average. PMID- 26901019 TI - Reliability of Shear-Wave Elastography Estimates of the Young Modulus of Tissue in Follicular Thyroid Neoplasms. AB - OBJECTIVE: The purpose of this study is to determine the reliability of shear wave elastographic estimates of the Young modulus in thyroid follicular neoplasms. SUBJECTS AND METHODS: In this study, 35 adults with follicular nodules diagnosed by fine-needle aspiration (FNA) biopsy were enrolled. A single sonographer examined all nodules in three planes (sagittal, transverse, and transverse center). Two raters independently placed ROIs in each nodule. Intra- and interrater reliability were computed as intraclass correlation coefficients (ICCs) and were reported using the Guidelines for Reporting Reliability and Agreement Studies. RESULTS: Thirty-five subjects with 35 follicular pattern nodules diagnosed by FNA biopsy were enrolled; 23 (65.7%) patients were female, with a mean age of 55.1 years (range, 23-85 years). For rater 1, intrarater agreement showed ICCs for single measurements of 0.87, 0.87, and 0.90 in the sagittal, transverse, and transverse center plans, respectively; ICCs for the median of multiple measurements were 0.97, 0.94, and 0.96 in the sagittal, transverse, and transverse center planes, respectively. For rater 2, intrarater agreement showed ICCs for single measurements of 0.94, 0.86, and 0.92 in the sagittal, transverse, and transverse center planes, respectively; ICCs for the median of multiple measurements were 0.97, 0.92, and 0.96 in the sagittal, transverse, and transverse center planes, respectively. Interrater agreement between measurements performed for the same subject showed ICCs for single measurements of 0.87, 0.87, and 0.80 in the sagittal, transverse, and transverse center planes, respectively; ICCs for the median of multiple measurements were 0.96, 0.93, and 0.92 in the sagittal, transverse, and transverse center planes, respectively. CONCLUSION: ROI placement is a reliable method for estimating the Young modulus of tissue in follicular thyroid nodules. PMID- 26901020 TI - Functional MRI of the Eustachian Tubes in Patients With Nasopharyngeal Carcinoma: Correlation With Middle Ear Effusion and Tumor Invasion. AB - OBJECTIVE: We sought to combine the Valsalva maneuver with MRI to evaluate eustachian tube function in patients with nasopharyngeal carcinoma (NPC) and to correlate the extent of tumor invasion with the presence of middle ear effusion (MEE) and eustachian tube dysfunction (ETD). SUBJECTS AND METHODS: We performed MRI along the lengths of the eustachian tubes, before and after the Valsalva maneuver was performed, in 53 patients with untreated NPC. The images were reviewed by two radiologists. RESULTS: A total of 106 eustachian tubes and middle ears were studied. There was dysfunction in 37 eustachian tubes, which was always ipsilateral to the NPC. There was MEE in 26 ears of 22 patients. In all cases of MEE, there was ipsilateral ETD. ETD was correlated with tumor invasion of the ipsilateral pharyngeal recess (p < 0.001), pharyngeal opening of the eustachian tube (p < 0.001), the cartilaginous eustachian tube (p < 0.001), the eustachian cartilage (p < 0.001), Ostmann fat pad (p < 0.001), the levator veli palatine muscle (p < 0.001), and the tensor veli palatine muscle (p < 0.001). There was a strong correlation between the grade of parapharyngeal space invasion and ETD (r = 0.809; p < 0.001) and MEE (r = 0.693; p < 0.001). CONCLUSION: Combining the Valsalva maneuver with MRI is helpful in assessing the function of the eustachian tube in patients with NPC. The cause of MEE in patients with NPC is dysfunction of the eustachian tube opening, which is associated with tumor invasion around the eustachian tube. PMID- 26901021 TI - Assessment of Sequential PET/MRI in Comparison With PET/CT of Pediatric Lymphoma: A Prospective Study. AB - OBJECTIVE: The objective of our study was to compare the diagnostic performance of sequential (18)F-FDG PET/MRI (PET/MRI) and (18)F-FDG PET/CT (PET/CT) in a pediatric cohort with lymphoma for lesion detection, lesion classification, and disease staging; quantification of FDG uptake; and radiation dose. SUBJECTS AND METHODS: For this prospective study of 25 pediatric patients with lymphoma, 40 PET/CT and PET/MRI examinations were performed after a single-injection dual-time point imaging protocol. Lesions detected, lesion classification, Ann Arbor stage, and radiation dose were tabulated for each examination, and statistical evaluations were performed to compare the modalities. Quantification of standardized uptake values (SUVs) was performed for all lesions. All available examinations and clinical history were used as the reference standard. RESULTS: No statistically significant differences between PET/MRI and PET/CT were observed in lesion detection rates, lesion classification, or Ann Arbor staging. Fifty four regions of focal uptake were observed on PET/MRI compared with 55 on PET/CT. Both modalities accurately classified 82% of the lesions relative to the reference standard. Disease staging based on PET/MRI was correct for 35 of the 40 studies, and disease staging based on PET/CT was correct for 35 of the 40 studies; there was substantial agreement between the modalities for disease staging (kappa = 0.684; p < 0.001). PET SUVs were strongly correlated between PET/CT and PET/MRI (rho > 0.72), although PET/MRI showed systematically lower SUV measurements. PET/MRI offered an average 45% reduction in radiation dose relative to PET/CT. CONCLUSION: In a pediatric cohort with lymphoma, sequential PET/MRI showed lesion detection, lesion classification, and Ann Arbor staging comparable to PET/CT. PET/MRI quantification of FDG uptake strongly correlated with PET/CT, but the SUVs were not interchangeable. PET/MRI significantly reduced radiation exposure and is a promising new alternative in the care of pediatric lymphoma patients. PMID- 26901022 TI - Acute Pancreatitis in Pediatric Patients: Demographics, Etiology, and Diagnostic Imaging. AB - OBJECTIVE: The objective of this article is to provide updates on acute pancreatitis in children regarding the imaging findings, causes, and complications based on a review of the current studies in the pediatrics literature. We discuss the epidemiology of acute pancreatitis, the role of imaging and imaging findings in the diagnosis of acute pancreatitis, and the causes and complications of acute pancreatitis. CONCLUSION: The incidence of acute pancreatitis is increasing in children. Imaging plays an important role in the diagnosis of acute pancreatitis because imaging findings can be used to establish the cause of acute pancreatitis, evaluate for complications of acute pancreatitis, and possibly predict the course of the disease. PMID- 26901023 TI - Conventional Ethiodized Oil Transarterial Chemoembolization for Treatment of Hepatocellular Carcinoma: Contemporary Single-Center Review of Clinical Outcomes. AB - OBJECTIVE: The purpose of this study is to investigate the outcomes of conventional transarterial chemoembolization (TACE) treatment of hepatocellular carcinoma (HCC) in contemporary clinical practice. MATERIALS AND METHODS: In this single-institution retrospective study, 188 patients underwent conventional TACE for HCC between 2007 and 2013. Medical record and imaging review was used to collect baseline demographic and disease data, tumor response, time to progression (TTP), and progression-free survival (PFS) outcomes, as well as transplant-free survival, calculated from the time of the first conventional TACE treatment. Data were censored in April 2014. RESULTS: The study cohort included 140 men and 48 women (mean age, 60 years; Barcelona Clinic Liver Cancer [BCLC] stage 0 = 5%, BCLC stage A = 41%, BCLC stage B = 28%, BCLC stage C = 15%, and BCLC stage D = 11%) with 207 index tumors (mean size, 4.0 cm; 11% with portal vein invasion) treated with a mean of 1.6 selective (79%) or lobar (21%) conventional TACE sessions. Concurrent thermal ablation was performed for 19% of patients. Objective response rates included size response in 29% (World Health Organization) and 28% (Response Evaluation Criteria for Solid Tumors [RECIST]) of patients, and necrosis response in 79% (European Association for the Study of the Liver) and 70% (modified RECIST) of patients. Median local TTP, distant site TTP, local PFS, and other site PFS were 51.7, 11.2, 10.8, and 10.5 months. Eighteen percent of patients underwent liver transplantation; 48% of United Network for Organ Sharing stage T3 tumors were downstaged to stage T2. Transplant-free survival for the entire cohort was 16.8 months (not reached, 33.9, 16.0, 4.4, and 6.9 months for BCLC stages 0, A, B, C, and D, respectively). Postembolization syndrome requiring extended hospital stay or readmission occurred in only 6% of patients. CONCLUSION: Conventional TACE is effective and safe for HCC therapy and may confer a survival benefit. The current data are in line with reported conventional TACE outcomes, and the minor postembolization syndrome incidence supports the low morbidity of this approach. PMID- 26901024 TI - Safety and Accuracy of Percutaneous Image-Guided Core Biopsy of the Spleen. AB - OBJECTIVE: The purpose of this study is to assess the complication rate and diagnostic accuracy of percutaneous image-guided core needle biopsy (CNB) of the spleen at a single center over the course of 12 years. MATERIALS AND METHODS: A retrospective review of an institutionally maintained biopsy database was used to identify CNBs of the spleen performed between October 2002 and January 2015. Clinical notes were reviewed from the date of biopsy to 3 months after biopsy to ascertain whether any immediate or delayed complications had occurred. Minor complications included pain requiring analgesia and incidental asymptomatic bleeding. Major complications were those scored at or above grade 3 according to the National Institutes of Health's Common Terminology Criteria for Adverse Events, version 4.0. The pathology reports issued for each specimen were evaluated and compared with results obtained from splenectomy, biopsy performed at another anatomic site, or longitudinal clinical or imaging follow-up. Sensitivity, specificity, and accuracy were calculated. RESULTS: A total of 97 CNBs of the spleen were performed, 23 of which were CT guided and 74 of which were ultrasound guided. There were seven (7.2%) minor complications and a single (1.0%) major complication; the overall complication rate was 8.2% (n = 8). The diagnostic yield-defined as adequate tissue to establish a diagnosis-of CNB was 93.8%, the sensitivity was 90.7%, the specificity was 100%, and the accuracy was 94.5%. CONCLUSION: Percutaneous image-guided CNB of the spleen is safe and effective in achieving a tissue diagnosis. PMID- 26901025 TI - Imaging Features Associated With Posttraumatic Breast Neuromas. AB - OBJECTIVE: The aim of this study is to review the clinical and imaging features of patients with a histopathologic diagnosis of posttraumatic breast neuromas. MATERIALS AND METHODS: We report eight biopsy-proven posttraumatic neuromas in six patients with a history of breast surgery. Mammographic, sonographic, and breast MRI examinations were reviewed according to the BI-RADS lexicon. In addition, the tail sign, a specific sign known to be associated with neuromas in other parts of the body, was assessed. RESULTS: Mammographic, MRI, and sonographic examinations were performed in three, four and all six patients, respectively. The neuromas were occult on the three mammograms performed but all of them were identified on ultrasound as hypoechoic masses with parallel orientation; seven of the eight neuromas (87.5%) had an oval shape with circumscribed margins. Strain elastography performed for two patients (three neuromas) showed benign features (benign elasticity scores and fat-to-lesion ratio). Half of the masses showed a tail sign (focal thickening of the nerve adjacent to posttraumatic neuroma, similar to the dural tail sign). Of five lesions investigated by MRI, two were occult on MRI. The remaining three were visible as isointense foci on T1-weighted images, with a benign type 1 enhancement curve. CONCLUSION: In patients who underwent breast surgery, a mass with benign features raises the possibility of a neuroma. Although the tail sign was present in half of the posttraumatic neuromas, imaging-guided biopsy remains the standard of care. PMID- 26901027 TI - Children's Clinic. PMID- 26901028 TI - Corrections. PMID- 26901026 TI - Reassessment and Follow-Up Results of BI-RADS Category 3 Lesions Detected on Screening Breast Ultrasound. AB - OBJECTIVE: The purpose of this study is to determine the frequency and the malignancy rate of BI-RADS category 3 lesions detected on screening breast ultrasound and to reassess whether they satisfied the requirements of the American College of Radiology Imaging Network (ACRIN) 6666 protocol. MATERIALS AND METHODS: Of 28,796 asymptomatic women who underwent screening mammography during 2 years, 12,187 underwent additional ultrasound as part of the screening. Patients for whom BI-RADS category 3 lesions were seen on the ultrasound were selected. We reviewed the initial ultrasound showing BI-RADS category 3 lesions and mammograms. We also investigated the clinical outcome of these lesions using the reference standard of a combination of pathologic analysis and follow-up for at least 24 months. RESULTS: The frequency of BI-RADS category 3 lesions detected on screening ultrasound was 14.6% (1783/12,187). Of the 1164 patients with a follow-up duration of at least 24 months or whose lesions were biopsied, eight were eventually proven to have malignancy (0.7%). The malignancy rate was 2.2% (4/184) for patients with abnormal mammograms and 0.4% (4/980) for those with normal mammograms. When the ACRIN 6666 protocols were strictly applied, 225 (19.3%) lesions were retrospectively recategorized as BI-RADS category 4 (n = 12) or category 2 (n = 213). All detected malignancies were early breast cancers with no lymph node metastasis. CONCLUSION: Although the frequency of ultrasound BI RADS category 3 lesions is considerably high (14.6%), the malignancy rate is very low (0.7%), especially in patients with a normal mammogram. Therefore, with BI RADS category 3 assessment, careful evaluation is required to avoid unnecessary short-interval follow-up or biopsy. PMID- 26901029 TI - Medicolegal--Malpractice and Ethical Issues in Radiology. PMID- 26901030 TI - Whole-Body MRI Screening in Children With Li-Fraumeni and Other Cancer Predisposition Syndromes. PMID- 26901031 TI - Reply to "Whole-Body MRI Screening in Children With Li-Fraumeni and Other Cancer Predisposition Syndromes.". PMID- 26901032 TI - The Half-Moon Sign of the Femoral Neck Is Nonspecific for the Diagnosis of Osteoid Osteoma. PMID- 26901033 TI - Reply to "The Half-Moon Sign of the Femoral Neck Is Nonspecific for the Diagnosis of Osteoid Osteoma.". PMID- 26901034 TI - How MALDI-TOF mass spectrometry can aid diagnosis of hard-to-identify pathogenic bacteria. PMID- 26901035 TI - The Prevalence of Metabolic Syndrome Using Three Different Diagnostic Criteria among Low Earning Nomadic Kazakhs in the Far Northwest of China: New Cut-Off Points of Waist Circumference to Diagnose MetS and Its Implications. AB - BACKGROUND: Although the epidemic of metabolic syndrome (MetS) has aroused wide public concern, most studies on MetS tend to examine urban and high income settings, and few studies cover nomadic areas and low earning populations. This research aims to investigate the prevalence of MetS and explore the cut-off point of waist circumference in a nomadic minority typical of low income populations in the remote northwest region of China. METHODS: A cross-sectional study was performed in a representative sample of 3900 Kazakh adults aged 18-84 years from 2009-2010. Three widely used criteria (ATP III?IDF?JIS) were employed to estimate the prevalence of MetS in Kazakhs to compare them with other populations. Receiver operator characteristic (ROC) curve analysis was used to explore the optimal cut-off values of waist circumference. RESULTS: The age-adjusted prevalence of MetS was 13.8%, 20.9%, and 24.8% based on the ATP III, IDF, and JIS criteria, respectively. The prevalence of MetS was higher in women and increased with age. Except for reduced HDL-cholesterol, the risk of other components of MetS increased with waist circumference enlargement. The cut-off point of waist circumference in screening at least two other components of MetS was 88 cm in men (Sensitivity = 61.1%, Specificity = 62.1%, ROC Curve Distance = 0.54) and 83 cm in women (Sensitivity = 60.0%, Specificity = 59.6%, ROC Curve Distance = 0.57). CONCLUSION: The prevalence of MetS in Kazakhs is higher than the national level of China and falls in between the Euro-American and Asia levels, as their cut-off points of waist circumference differ from that recommended for Chinese. We suggest a cost-effective strategy to screen for MetS and prevent cardiovascular disease using new cut-off points of waist circumference in low earning nomadic Kazakhs. PMID- 26901036 TI - Alleles of HLA-DRB1*04 Associated with Pulmonary Tuberculosis in Amazon Brazilian Population. AB - Immunogenetic host factors are associated with susceptibility or protection to tuberculosis (TB). Strong associations of HLA class II genes with TB are reported. We analyzed the HLA-DRB1*04 alleles to identify subtypes associated with pulmonary TB and their interaction with risk factors such as alcohol, smoking, and gender in 316 pulmonary TB patients and 306 healthy individuals from the Brazilian Amazon. The HLA-DRB1*04 was prevalent in patients with pulmonary TB (p<0.0001; OR = 2.94; 95% CI = 2.12 to 4.08). Direct nucleotide sequencing of DRB1 exon 2 identified nine subtypes of HLA-DRB1*04. The subtype HLA DRB1*04:11:01 (p = 0.0019; OR = 2.23; 95% CI = 1.34 to 3.70) was associated with susceptibility to pulmonary TB while DRB1*04:07:01 (p<0.0001; OR = 0.02; 95% CI = 0.001 to 0.33) to protection. Notably, the interaction between alcohol and HLA DRB1*04:11:01 increased the risk for developing pulmonary TB (p = 0.0001; OR = 51.3; 95% CI = 6.81 to 386). Multibacillary pulmonary TB, the clinical presentation of disease transmission, was strongly associated with interaction to alcohol (p = 0.0026; OR = 11.1; 95% CI = 3.99 to 30.9), HLA-DRB1*04:11:01 (p = 0.0442; OR = 2.01; 95% CI = 1.03 to 3.93) and DRB1*04:92 (p = 0.0112; OR = 8.62; 95% CI = 1.63 to 45.5). These results show that HLA-DRB1*04 are associated with pulmonary TB. Interestingly, three subtypes, DRB1*04:07:01, DRB1*04:11:01 and DRB1*04:92 of the HLA-DRB1*04 could be potential immunogenetic markers that may help to explain mechanisms involved in disease development. PMID- 26901037 TI - Effects of Intra-Operative Total Intravenous Anaesthesia with Propofol versus Inhalational Anaesthesia with Sevoflurane on Post-Operative Pain in Liver Surgery: A Retrospective Case-Control Study. AB - BACKGROUND: Patients receiving total intravenous anesthesia (TIVA) with propofol have been shown to experience less postoperative pain. We evaluated the post operative analgesic effects of propofol compared with sevoflurane maintenance of anesthesia in liver surgery. This study was registered at ClinicalTrials.gov (NCT02179437). METHODS: In this retrospective study, records of patients who underwent liver surgery between 2010 and 2013 were reviewed. Ninety-five patients anesthetized with propofol TIVA were matched with 95 patients anesthetized with sevoflurane. Numeric pain rating scale (NRS) pain scores, postoperative morphine consumption, side effects and patients' satisfaction with pain relief were evaluated. RESULTS: The TIVA group reported lower NRS pain scores during coughing on postoperative days 1 and 2 but not 3 (p = 0.0127, p = 0.0472, p = 0.4556 respectively). They also consumed significantly less daily (p = 0.001 on day 1, p = 0.0231 on day 2, p = 0.0004 on day 3), accumulative (p = 0.001 on day 1, p<0.0001 on day 2 and p = 0.0064 on day 3) and total morphine (p = 0.03) when compared with the sevoflurane group. There were no differences in total duration of intravenous patient controlled analgesia (PCA) morphine use and patient satisfaction. No difference was found in reported side effects. CONCLUSION: Patients anesthetized with propofol TIVA reported less pain during coughing and consumed less daily, accumulative and total morphine after liver surgery. PMID- 26901038 TI - Association between maternal age at conception and risk of idiopathic clubfoot. AB - Background and purpose - Results from case-control studies of maternal age at conception and risk of idiopathic clubfoot have been inconsistent. We conducted a meta-analysis to determine whether there is any association between maternal age at conception and the morbidity of idiopathic clubfoot. Methods - We searched PubMed-MEDLINE, EMBASE, and the Cochrane Library up to June 2015 and supplemented the search with manual searches of the reference lists of the articles identified. 11 studies published between 1990 and 2015 were pooled. We investigated heterogeneity in maternal age and whether publication bias might have affected the results. Results - Compared to a control group, maternal age at conception of between 20 and 24 years old was associated with an increased risk of occurrence of clubfoot (OR = 1.2, 95% CI: 1.1-1.4). No such association was found for the age groups of >= 35, 30-34, 25-29, and < 20 years. There was no heterogeneity in the age groups of >= 35, 30-34, and 20-24 years, moderate heterogeneity in the 25- to 29-year age group, and a large degree of heterogeneity in the group that was < 20 years of age. The prediction intervals for the age groups of 25-29 and < 20 years were 0.56 to 1.3 and -0.39 to 2.4, respectively. We found no evidence of significant publication bias. Interpretation - From the results of this meta-analysis of 11 studies, maternal age at conception between 20 to 24 years of age appears to be associated with an increased risk of occurrence of clubfoot. PMID- 26901040 TI - [Birth weight of newborns and health behaviours and haematological parameters of pregnant women - results of preliminary studies]. PMID- 26901039 TI - Wnt-YAP interactions in the neural fate of human pluripotent stem cells and the implications for neural organoid formation. AB - Human pluripotent stem cells (hPSCs) have shown the ability to self-organize into different types of neural organoids (e.g., whole brain organoids, cortical spheroids, midbrain organoids etc.) recently. The extrinsic and intrinsic signaling elicited by Wnt pathway, Hippo/Yes-associated protein (YAP) pathway, and extracellular microenvironment plays a critical role in brain tissue morphogenesis. This article highlights recent advances in neural tissue patterning from hPSCs, in particular the role of Wnt pathway and YAP activity in this process. Understanding the Wnt-YAP interactions should provide us the guidance to predict and modulate brain-like tissue structure through the regulation of extracellular microenvironment of hPSCs. PMID- 26901041 TI - [Are children from resort spa healthy? The overweight and obesity in children from Kudowa-Zdroj]. AB - ABSTRACT: Overweight and obesity are becoming a more and more common problem among children and teenagers. AIM: . The aim of this study is to evaluate the development of children and teenagers from Kudowa-Zdroj and to assess the prevalence of overweight and obesity in this population. MATERIALS AND METHODS: . The study included 545 children, aged 5-16 years from Kudowa-Zdroj. The following anthropometric parameters were assessed: body weight and height, BMI, Quetelet index, Rohrer's index, waist circumference, hip circumference and waist to height ratio (WHtR). RESULTS: . Overweight or obesity diagnosed by BMI SDS were observed in 26.7% of children from grades 0-3, 22.02% of children from grades 4-6 and 22.52% of Junior High School students. Students in grades 0-3 (mean 0.95 +/- 2.17) achieved higher BMI SDS compared to students in grades 4-6 (mean 0.37 +/- 1.71) and secondary school (mean 0.65 +/- 1.61) (p= 0.023).Overweight or obesity diagnosed by Rohrer index SDS and Quetelet index SDS were observed in 22,84% and 17,13% children. Elevated value of the hip circumference SDS was found in 19.48% of children and waist circumference SDS was increased in 17.5% of children. In the group of children with overweight and obesity 59.4% had elevated waist circumference SDS and 53.4% waist circumference SDS. WHtR was elevated in 8.3% of children, more often in boys (p <0.001), 3.1% of girls and 13.07% of boys. CONCLUSIONS: . The BMI is the best index for diagnosis of overweight and obesity. Overweight and obesity are common disorders among children from Kudowa-Zdroj. It is recommended to educate children, adolescence and their family about healthy lifestyle in order to reduce the prevalence of overweight and obesity. PMID- 26901042 TI - [Assessments of dietary patterns of children aged 10-12 in the city of Olsztyn]. AB - MATERIAL AND METHODS: The aim of the research was to evaluate the dietary patterns of children aged 10-12 in the city of Olsztyn. The research involved a group of 288 children (144 boys and 144 girls) aged 10-12, living in the city of Olsztyn. Evaluation of dietary patterns was carried out on the basis of individual dietary interviews concerning food intake over the past 24h, followed by determination of energy and nutritional values of the daily diet as well as the content of basic nutrients, such as protein, fat, carbohydrates, microelements and vitamins. RESULTS: The research demonstrated that although the amount of consumed meals was correct, they did not cover the energy requirements of the examined children (in the case of boys, the average energy value of the daily diet was 1960,92 kcal, and for girls it was 1627,7 kcal) and were too poor in protein and carbohydrates. Moreover, it was found that the calcium intake norms were met at the level of approximately 50% of the average demand and an excessively low content of fibre were found in the daily diet. CONCLUSIONS: The study results showed the mistakes made by the studied population group in the method of nutrition, including daily diet energy value (deficiencies), its structure and the quality of the meals. PMID- 26901043 TI - Metabolicsyndrome in youngpatients. PMID- 26901044 TI - [Gene polymorphism and dyslipidemias]. PMID- 26901045 TI - [Congenital hyperinsulinism: course and consequences - case report]. PMID- 26901046 TI - Which Genetics Variants in DNase-Seq Footprints Are More Likely to Alter Binding? AB - Large experimental efforts are characterizing the regulatory genome, yet we are still missing a systematic definition of functional and silent genetic variants in non-coding regions. Here, we integrated DNaseI footprinting data with sequence based transcription factor (TF) motif models to predict the impact of a genetic variant on TF binding across 153 tissues and 1,372 TF motifs. Each annotation we derived is specific for a cell-type condition or assay and is locally motif driven. We found 5.8 million genetic variants in footprints, 66% of which are predicted by our model to affect TF binding. Comprehensive examination using allele-specific hypersensitivity (ASH) reveals that only the latter group consistently shows evidence for ASH (3,217 SNPs at 20% FDR), suggesting that most (97%) genetic variants in footprinted regulatory regions are indeed silent. Combining this information with GWAS data reveals that our annotation helps in computationally fine-mapping 86 SNPs in GWAS hit regions with at least a 2-fold increase in the posterior odds of picking the causal SNP. The rich meta information provided by the tissue-specificity and the identity of the putative TF binding site being affected also helps in identifying the underlying mechanism supporting the association. As an example, the enrichment for LDL level associated SNPs is 9.1-fold higher among SNPs predicted to affect HNF4 binding sites than in a background model already including tissue-specific annotation. PMID- 26901047 TI - Serum TGF-beta1 as a Biomarker for Type 2 Diabetic Nephropathy: A Meta-Analysis of Randomized Controlled Trials. AB - BACKGROUND: Abnormal expression of serum TGF-beta1 was found in patients with diabetic nephropathy. However, the association of TGF-beta1 with the risk of diabetic nephropathy remains unknown. The present study was undertaken to investigate whether such an association exists. METHODS: We searched the Chinese VIP, Wangfang, China National Knowledge Infrastructure, PubMed, Embase, and Google Scholar databases for relevant studies and extracted all eligible data. Stata12 software was used for statistical analysis. RESULTS: Nine reports met our criteria and were used for data extraction. There were 264 patients and 227 healthy controls from qualified reports in this meta-analysis. The results suggested that serum TGF-beta1 levels were significantly up-regulated in patients with diabetic nephropathy; the instrumental variable was 3.94 (95% confidence interval 3.20-4.68, p<0.01). CONCLUSIONS: Meta-analysis suggested that elevated serum TGF-beta level in patients with diabetes is associated with a high risk of nephropathy. Further studies are required to validate these observations. PMID- 26901048 TI - The Association of Medication-Use and Frailty-Related Factors with Gait Performance in Older Patients. AB - The increased fall risk associated with the use of psychotropic drugs might be caused by underlying problems in postural control that are induced by sedative side-effects of these drugs. The current literature on the effects of psychotropics on postural control only examined acute single-drug effects, and included relatively healthy young elderly. Consequently, it is unclear what the impact of the long-term use of these drugs is on gait in frail older persons with polypharmacy. Therefore, it was aimed in the present study to explore the association between the use of psychotropics, multiple other medications, frailty related parameters and gait performance in older patients. Eighty older persons (79+/-5.6 years) were recruited. Comorbid diseases, frailty-related parameters, and medication-use were registered. Trunk accelerations during a 3-minute-walking task were recorded, whereof walking speed, mean stride times, coefficient of variation (CV) of stride times, and step consistency were determined. Multivariate Partial Least Squares (PLS) regression analysis was used to examine the association between population characteristics and medication-use, versus gait parameters. A PLS-model existing of four latent variables was built, explaining 45% of the variance in four gait parameters. Frailty-related factors, being female, and laxative-use were most strongly associated with lower walking speed, higher mean stride times, higher CV of stride times, and less consistent steps. In conclusion, frailty-related parameters were stronger associated with impaired gait performance than the use of psychotropic drugs. Possibly, at a certain frailty-level, the effect of the deterioration in physical functioning in frailty is so large, that the instability-provoking side-effects of psychotropic drugs have less impact on gait. PMID- 26901049 TI - A Molecular Method to Discriminate between Mass-Reared Sterile and Wild Tsetse Flies during Eradication Programmes That Have a Sterile Insect Technique Component. AB - BACKGROUND: The Government of Senegal has embarked several years ago on a project that aims to eradicate Glossina palpalis gambiensis from the Niayes area. The removal of the animal trypanosomosis would allow the development more efficient livestock production systems. The project was implemented using an area-wide integrated pest management strategy including a sterile insect technique (SIT) component. The released sterile male flies originated from a colony from Burkina Faso. METHODOLOGY/PRINCIPAL FINDINGS: Monitoring the efficacy of the sterile male releases requires the discrimination between wild and sterile male G. p. gambiensis that are sampled in monitoring traps. Before being released, sterile male flies were marked with a fluorescent dye powder. The marking was however not infallible with some sterile flies only slightly marked or some wild flies contaminated with a few dye particles in the monitoring traps. Trapped flies can also be damaged due to predation by ants, making it difficult to discriminate between wild and sterile males using a fluorescence camera and / or a fluorescence microscope. We developed a molecular technique based on the determination of cytochrome oxidase haplotypes of G. p. gambiensis to discriminate between wild and sterile males. DNA was isolated from the head of flies and a portion of the 5' end of the mitochondrial gene cytochrome oxidase I was amplified to be finally sequenced. Our results indicated that all the sterile males from the Burkina Faso colony displayed the same haplotype and systematically differed from wild male flies trapped in Senegal and Burkina Faso. This allowed 100% discrimination between sterile and wild male G. p. gambiensis. CONCLUSIONS/SIGNIFICANCE: This tool might be useful for other tsetse control campaigns with a SIT component in the framework of the Pan-African Tsetse and Trypanosomosis Eradication Campaign (PATTEC) and, more generally, for other vector or insect pest control programs. PMID- 26901050 TI - Continental Island Formation and the Archaeology of Defaunation on Zanzibar, Eastern Africa. AB - With rising sea levels at the end of the Pleistocene, land-bridge or continental islands were formed around the world. Many of these islands have been extensively studied from a biogeographical perspective, particularly in terms of impacts of island creation on terrestrial vertebrates. However, a majority of studies rely on contemporary faunal distributions rather than fossil data. Here, we present archaeological findings from the island of Zanzibar (also known as Unguja) off the eastern African coast, to provide a temporal perspective on island biogeography. The site of Kuumbi Cave, excavated by multiple teams since 2005, has revealed the longest cultural and faunal record for any eastern African island. This record extends to the Late Pleistocene, when Zanzibar was part of the mainland, and attests to the extirpation of large mainland mammals in the millennia after the island became separated. We draw on modeling and sedimentary data to examine the process by which Zanzibar was most recently separated from the mainland, providing the first systematic insights into the nature and chronology of this process. We subsequently investigate the cultural and faunal record from Kuumbi Cave, which provides at least five key temporal windows into human activities and faunal presence: two at the end of the Last Glacial Maximum (LGM), one during the period of post-LGM rapid sea level rise and island formation, and two in the late Holocene (Middle Iron Age and Late Iron Age). This record demonstrates the presence of large mammals during the period of island formation, and their severe reduction or disappearance in the Kuumbi Cave sequence by the late Holocene. While various limitations, including discontinuity in the sequence, problematize attempts to clearly attribute defaunation to anthropogenic or island biogeographic processes, Kuumbi Cave offers an unprecedented opportunity to examine post-Pleistocene island formation and its long-term consequences for human and animal communities. PMID- 26901051 TI - Intravital Fluorescence Excitation in Whole-Animal Optical Imaging. AB - Whole-animal fluorescence imaging with recombinant or fluorescently-tagged pathogens or cells enables real-time analysis of disease progression and treatment response in live animals. Tissue absorption limits penetration of fluorescence excitation light, particularly in the visible wavelength range, resulting in reduced sensitivity to deep targets. Here, we demonstrate the use of an optical fiber bundle to deliver light into the mouse lung to excite fluorescent bacteria, circumventing tissue absorption of excitation light in whole-animal imaging. We present the use of this technology to improve detection of recombinant reporter strains of tdTomato-expressing Mycobacterium bovis BCG (Bacillus Calmette Guerin) bacteria in the mouse lung. A microendoscope was integrated into a whole-animal fluorescence imager to enable intravital excitation in the mouse lung with whole-animal detection. Using this technique, the threshold of detection was measured as 103 colony forming units (CFU) during pulmonary infection. In comparison, the threshold of detection for whole-animal fluorescence imaging using standard epi-illumination was greater than 106 CFU. PMID- 26901054 TI - Advanced Analysis of Pharmaco-Sleep Data in Humans. AB - Pharmaco-sleep studies in humans aim at the description of the effects of drugs, most frequently substances that act on the central nervous system, by means of quantitative analysis of biosignals recorded in subjects during sleep. Up to 2007, the only standard for the classification of sleep macrostructure that found worldwide acceptance were the rules published in 1968 by Rechtschaffen and Kales. In May 2007, the AASM Manual for the Scoring of Sleep and Associated Events was published by the American Academy of Sleep Medicine, and concerning the classification of sleep stages, these new rules are supposed to replace those developed by Rechtschaffen and Kales. As compared to the rather low interrater reliability of manual sleep scoring, semiautomated approaches may achieve a reliability close to 1 (Cohen's kappa 0.99 for 2 semiautomated scorings as compared to 0.76 for 2 manual scorings) without any decline in validity. Depending on the aim of the pharmaco-sleep study, additional analyses concerning sleep fragmentation, sleep microstructure, sleep depth, sleep processes and local aspects of sleep should be considered. For some of these additional features, rules for visual scoring have been established, while for others automatic analysis is obligatory. Generally, for reasons of cost-effectiveness but also reliability, automatic analysis is preferable to visual analysis. However, the validity of the automatic method applied has to be proven. PMID- 26901053 TI - Overall Survival Endpoint in Oncology Clinical Trials: Addressing the Effect of Crossover--The Case of Pazopanib in Advanced Renal Cell Carcinoma. AB - OBJECTIVE: To identify the issues of using overall survival (OS) as a primary endpoint in the presence of crossover and the statistical analyses available to adjust for confounded OS due to crossover in oncology clinical trials. METHODS: An indirect comparison was conducted between pazopanib and sunitinib in advanced renal cell carcinoma. Statistical adjustment methods were used to estimate the true comparative effectiveness of these treatments. Recently, a head-to-head trial comparing pazopanib and sunitinib was completed. This provided the opportunity to compare the OS treatment effect estimated for pazopanib versus sunitinib using indirect comparison and statistical adjustment techniques with that observed in the head-to-head trial. RESULTS: Using a rank-preserving structural failure time model to adjust for crossover in the pazopanib registration trial, the indirect comparison of pazopanib versus sunitinib resulted in an OS hazard ratio (HR) of 0.97, while an unadjusted analysis resulted in an OS HR of 1.96. The head-to-head trial reported a final OS HR of 0.92 for pazopanib versus sunitinib. CONCLUSION: This case study supports the need to adjust for confounded OS due to crossover, which enables trials to meet ethical standards and provides decision makers with a more accurate estimate of treatment benefit. PMID- 26901052 TI - The Brain Network of Naming: A Lesson from Primary Progressive Aphasia. AB - OBJECTIVE: Word finding depends on the processing of semantic and lexical information, and it involves an intermediate level for mapping semantic-to lexical information which also subserves lexical-to-semantic mapping during word comprehension. However, the brain regions implementing these components are still controversial and have not been clarified via a comprehensive lesion model encompassing the whole range of language-related cortices. Primary progressive aphasia (PPA), for which anomia is thought to be the most common sign, provides such a model, but the exploration of cortical areas impacting naming in its three main variants and the underlying processing mechanisms is still lacking. METHODS: We addressed this double issue, related to language structure and PPA, with thirty patients (11 semantic, 12 logopenic, 7 agrammatic variant) using a picture naming task and voxel-based morphometry for anatomo-functional correlation. First, we analyzed correlations for each of the three variants to identify the regions impacting naming in PPA and to disentangle the core regions of word finding. We then combined the three variants and correlation analyses for naming (semantic-to-lexical mapping) and single-word comprehension (lexical-to-semantic mapping), predicting an overlap zone corresponding to a bidirectional lexical semantic hub. RESULTS AND CONCLUSIONS: Our results showed that superior portions of the left temporal pole and left posterior temporal cortices impact semantic and lexical naming mechanisms in semantic and logopenic PPA, respectively. In agrammatic PPA naming deficits were rare, and did not correlate with any cortical region. Combined analyses revealed a cortical overlap zone in superior/middle mid temporal cortices, distinct from the two former regions, impacting bidirectional binding of lexical and semantic information. Altogether, our findings indicate that lexical/semantic word processing depends on an anterior-posterior axis within lateral-temporal cortices, including an anatomically intermediate hub dedicated to lexical-semantic integration. Within this axis our data reveal the underpinnings of anomia in the PPA variants, which is of relevance for both diagnosis and future therapy strategies. PMID- 26901055 TI - Post-H1N1 Flu Vaccination Narcolepsy in Switzerland: A Retrospective Survey in the 30 Sleep-Certified Swiss Centers. AB - Narcolepsy-cataplexy is a sleep-wake disorder and suggested to be immune mediated, involving genetic and environmental factors. The autoimmune process eventually leads to a loss of hypocretin neurons in the lateral hypothalamus. Epidemiological studies in several countries proved an increased incidence of narcolepsy after H1N1 flu vaccination and infection. This survey in 30 sleep centers in Switzerland led to the identification of 9 H1N1-vaccinated children and adults as newly diagnosed narcolepsy. Clinical features included the abrupt and severe onset of sleepiness, cataplexy and sleep fragmentation. PMID- 26901057 TI - Detection of changes in the ventral tegmental area of patients with schizophrenia using neuromelanin-sensitive MRI. AB - The ventral tegmental area (VTA), one of the neuromelanin-containing dopaminergic nuclei in the midbrain, is closely related to the pathogenesis of schizophrenia, but its imaging findings remain unclear. Here, we investigated whether neuromelanin-sensitive MRI can detect alterations in the signals of the VTA of patients with schizophrenia. Neuromelanin-sensitive T1-weighted images at 3 T were obtained in 14 patients with schizophrenia and 22 healthy individuals. After signal inhomogeneity correction, brain signal rescaling of the images, and spatial normalization, signal intensity of the VTA and substantia nigra pars compacta (SNc) was automatically measured using the regions-of-interest constructed from the images of the healthy individuals. The normalized signal intensity of the VTA in patients with schizophrenia (median +/- quartile deviation, 998 +/- 10) was significantly decreased compared with that in healthy controls (1018 +/- 15) (P=0.010), whereas that of the SNc was not significantly different between the groups (1093 +/- 6 and 1098 +/- 10, respectively, P=0.84). The VTA/SNc ratio was also significantly lower in patients with schizophrenia (0.916 +/- 0.007) than in the control participants (0.934 +/- 0.010) (P=0.010). In addition, the scores of the Scale for the Assessment of Positive Symptoms showed an independent negative correlation with VTA signaling (r=-0.69, P=0.012). Neuromelanin-sensitive MRI enables direct visualization of the selective signal attenuation in the VTA, which was correlated with positive symptoms, in patients with schizophrenia. PMID- 26901056 TI - A novel multiplex bead-based platform highlights the diversity of extracellular vesicles. AB - The surface protein composition of extracellular vesicles (EVs) is related to the originating cell and may play a role in vesicle function. Knowledge of the protein content of individual EVs is still limited because of the technical challenges to analyse small vesicles. Here, we introduce a novel multiplex bead based platform to investigate up to 39 different surface markers in one sample. The combination of capture antibody beads with fluorescently labelled detection antibodies allows the analysis of EVs that carry surface markers recognized by both antibodies. This new method enables an easy screening of surface markers on populations of EVs. By combining different capture and detection antibodies, additional information on relative expression levels and potential vesicle subpopulations is gained. We also established a protocol to visualize individual EVs by stimulated emission depletion (STED) microscopy. Thereby, markers on single EVs can be detected by fluorophore-conjugated antibodies. We used the multiplex platform and STED microscopy to show for the first time that NK cell derived EVs and platelet-derived EVs are devoid of CD9 or CD81, respectively, and that EVs isolated from activated B cells comprise different EV subpopulations. We speculate that, according to our STED data, tetraspanins might not be homogenously distributed but may mostly appear as clusters on EV subpopulations. Finally, we demonstrate that EV mixtures can be separated by magnetic beads and analysed subsequently with the multiplex platform. Both the multiplex bead-based platform and STED microscopy revealed subpopulations of EVs that have been indistinguishable by most analysis tools used so far. We expect that an in-depth view on EV heterogeneity will contribute to our understanding of different EVs and functions. PMID- 26901058 TI - Disrupting frontal eye-field activity impairs memory recall. AB - A large body of research demonstrated that participants preferably look back to the encoding location when retrieving visual information from memory. However, the role of this 'looking back to nothing' is still debated. The goal of the present study was to extend this line of research by examining whether an important area in the cortical representation of the oculomotor system, the frontal eye field (FEF), is involved in memory retrieval. To interfere with the activity of the FEF, we used inhibitory continuous theta burst stimulation (cTBS). Before stimulation was applied, participants encoded a complex scene and performed a short-term (immediately after encoding) or long-term (after 24 h) recall task, just after cTBS over the right FEF or sham stimulation. cTBS did not affect overall performance, but stimulation and statement type (object vs. location) interacted. cTBS over the right FEF tended to impair object recall sensitivity, whereas there was no effect on location recall sensitivity. These findings suggest that the FEF is involved in retrieving object information from scene memory, supporting the hypothesis that the oculomotor system contributes to memory recall. PMID- 26901059 TI - beta-Cell-Specific Mafk Overexpression Impairs Pancreatic Endocrine Cell Development. AB - The MAF family transcription factors are homologs of v-Maf, the oncogenic component of the avian retrovirus AS42. They are subdivided into 2 groups, small and large MAF proteins, according to their structure, function, and molecular size. MAFK is a member of the small MAF family and acts as a dominant negative form of large MAFs. In previous research we generated transgenic mice that overexpress MAFK in order to suppress the function of large MAF proteins in pancreatic beta-cells. These mice developed hyperglycemia in adulthood due to impairment of glucose-stimulated insulin secretion. The aim of the current study is to examine the effects of beta-cell-specific Mafk overexpression in endocrine cell development. The developing islets of Mafk-transgenic embryos appeared to be disorganized with an inversion of total numbers of insulin+ and glucagon+ cells due to reduced beta-cell proliferation. Gene expression analysis by quantitative RT-PCR revealed decreased levels of beta-cell-related genes whose expressions are known to be controlled by large MAF proteins. Additionally, these changes were accompanied with a significant increase in key beta-cell transcription factors likely due to compensatory mechanisms that might have been activated in response to the beta-cell loss. Finally, microarray comparison of gene expression profiles between wild-type and transgenic pancreata revealed alteration of some uncharacterized genes including Pcbd1, Fam132a, Cryba2, and Npy, which might play important roles during pancreatic endocrine development. Taken together, these results suggest that Mafk overexpression impairs endocrine development through a regulation of numerous beta-cell-related genes. The microarray analysis provided a unique data set of differentially expressed genes that might contribute to a better understanding of the molecular basis that governs the development and function of endocrine pancreas. PMID- 26901060 TI - The Role of Noninvasive Ventilation in Patients with "Do Not Intubate" Order in the Emergency Setting. AB - BACKGROUND: Noninvasive ventilation (NIV) is being used increasingly in patients who have a "do not intubate" (DNI) order. However, the impact of NIV on the clinical and health-related quality of life (HRQOL) in the emergency setting is not known, nor is its effectiveness for relieving symptoms in end-of-life care. OBJECTIVE: The aim of this prospective study was to determine the outcome and HRQOL impact of regular use of NIV outcomes on patients with a DNI order who were admitted to the emergency room department (ED). METHODS: Eligible for participation were DNI-status patients who receive NIV for acute or acute-on chronic respiratory failure when admitted to the ED of a tertiary care, university-affiliated, 600-bed hospital between January 2014 and December 2014. Patients were divided into 2 groups: (1) those whose DNI order related to a decision to withhold therapy and (2) those for whom any treatment, including NIV, was provided for symptom relief only. HRQOL was evaluated only in group 1, using the 12-item Short Form Health Survey (SF-12). Long-term outcome was evaluated 90 days after hospital discharge by means of a telephone interview. RESULTS: During the study period 1727 patients were admitted to the ED, 243 were submitted to NIV and 70 (29%) were included in the study. Twenty-nine (41%) of the 70 enrollees received NIV for symptom relief only (group2). Active cancer [7% vs 35%, p = 0,004] and neuromuscular diseases [0% vs. 17%] were more prevalent in this group. NIV was stopped in 59% of the patients in group 2 due to lake of clinical benefit. The in-hospital mortality rate was 37% for group 1 and 86% for group 2 0,001). Among patients who were discharged from hospital, 23% of the group 1 and all patients in group 2 died within 90 days. Relative to baseline, no significant decline in HRQOL occurred in group 1 by 90 days postdischarge. CONCLUSION: The survival rate was 49% among DNI-status patients for whom NIV was used as a treatment in ED, and these patients did not experience a decline in HRQOL throughout the study. NIV did not provide significant relief of symptoms in more than half the patients who receive it for that purpose. PMID- 26901061 TI - Sterile alpha Motif Domain Containing 9 Is a Novel Cellular Interacting Partner to Low-Risk Type Human Papillomavirus E6 Proteins. AB - Low-risk type human papillomavirus (HPV) 6 and 11 infection causes recurrent respiratory papillomatosis (RRP) and genital warts. RRP is the most common benign tumor of the larynx in children with frequent relapses. Repeated surgeries are often needed to improve vocal function and prevent life-threatening respiratory obstruction. Currently, there are no effective treatments available to completely eliminate these diseases, largely due to limited knowledge regarding their viral molecular pathogenesis. HPV E6 proteins contribute to cell immortalization by interacting with a variety of cellular proteins, which have been well studied for the high-risk type HPVs related to cancer progression. However, the functions of low-risk HPV E6 proteins are largely unknown. In this study, we report GST pulldown coupled mass spectrometry analysis with low-risk HPV E6 proteins that identified sterile alpha motif domain containing 9 (SAMD9) as a novel interacting partner. We then confirmed the interaction between HPV-E6 and SAMD9 using co immunoprecipitation, proximity ligation assay, and confocal immunofluorescence staining. The SAMD9 gene is down-regulated in a variety of neoplasms and deleteriously mutated in normophosphatemic familial tumoral calcinosis. Interestingly, SAMD9 also has antiviral functions against poxvirus. Our study adds to the limited knowledge of the molecular properties of low-risk HPVs and describes new potential functions for the low-risk HPV E6 protein. PMID- 26901062 TI - The Impacts of Inclusion in Clinical Trials on Outcomes among Patients with Metastatic Breast Cancer (MBC). AB - BACKGROUND: Metastatic breast cancer (MBC) remains a devastating and incurable disease. Over the past decade, the implementation of clinical trials both with and without molecular targeted therapeutics has impacted the daily clinical treatment of patients with MBC. In this study, we determine whether including MBC patients in clinical trials affects clinical outcomes. METHODS: We retrospectively reviewed data for a total of 863 patients diagnosed with initial or recurrent (after receiving adjuvant systemic treatments following surgery) metastatic disease between January 2000 and December 2013. Data were obtained from the breast cancer database of Samsung Medical Center. RESULTS: Among the 806 patients selected for inclusion, 188 (23%) had participated in clinical trials. A total of 185 clinical trials were conducted from 2000 to 2014. When compared with earlier periods (n = 10 for 2000-2004), clinical trial enrollment significantly increased over time (n = 103 for 2005-2009, P = 0.024; n = 110 for 2010-2014, P = 0.046). Multivariate analyses revealed that biologic subtype, distant recurrence free interval (DRFI), and clinical trial enrollment were independent predictors of overall survival. Patients who participated in clinical trials showed improved survival, with a hazard ratio of 0.75 (95% CI, 0.59-0.95), which was associated with a 25% reduction in the risk of death. However, subgroup analysis showed that this improved survival benefit was not maintained in patients with triple negative breast cancer (TNBC). CONCLUSIONS: Although not conclusive, we could speculate that there were differences in the use of newer agents or regimens over time, and these differences appear to be associated with improved survival. PMID- 26901063 TI - Application of Probabilistic Multiple-Bias Analyses to a Cohort- and a Case Control Study on the Association between PandemrixTM and Narcolepsy. AB - BACKGROUND: An increase in narcolepsy cases was observed in Finland and Sweden towards the end of the 2009 H1N1 influenza pandemic. Preliminary observational studies suggested a temporal link with the pandemic influenza vaccine PandemrixTM, leading to a number of additional studies across Europe. Given the public health urgency, these studies used readily available retrospective data from various sources. The potential for bias in such settings was generally acknowledged. Although generally advocated by key opinion leaders and international health authorities, no systematic quantitative assessment of the potential joint impact of biases was undertaken in any of these studies. METHODS: We applied bias-level multiple-bias analyses to two of the published narcolepsy studies: a pediatric cohort study from Finland and a case-control study from France. In particular, we developed Monte Carlo simulation models to evaluate a potential cascade of biases, including confounding by age, by indication and by natural H1N1 infection, selection bias, disease- and exposure misclassification. All bias parameters were evidence-based to the extent possible. RESULTS: Given the assumptions used for confounding, selection bias and misclassification, the Finnish rate ratio of 13.78 (95% CI: 5.72-28.11) reduced to a median value of 6.06 (2.5th- 97.5th percentile: 2.49-15.1) and the French odds ratio of 5.43 (95% CI: 2.6-10.08) to 1.85 (2.5th-97.5th percentile: 0.85-4.08). CONCLUSION: We illustrate multiple-bias analyses using two studies on the PandemrixTM-narcolepsy association and advocate their use to better understand the robustness of study findings. Based on our multiple-bias models, the observed PandemrixTM-narcolepsy association consistently persists in the Finnish study. For the French study, the results of our multiple-bias models were inconclusive. PMID- 26901064 TI - From first love to marriage and maturity: a life-course perspective on HIV risk among young Swazi adults. AB - This paper uses a life-course approach to explore the sexual partnerships and HIV related risk of men and women in Swaziland throughout their adolescence, 20s and 30s. Twenty-eight Swazi men and women between the ages of 20 and 39 discussed their life histories in 117 in-depth interviews, with an average follow-up of nine months. Many participants described painful childhood experiences, including a lack of positive role models for couple relationships. Women's first sexual partnerships often involved coercion or force and resulted in pregnancy and abandonment by partners, leaving women economically vulnerable. Most men and women reported a desire to marry and associated marriage with respectability and monogamy. Men typically did not feel ready to marry until their 30s, while women often married only after years in tumultuous relationships. A high degree of relationship instability and change was observed over the study period, with half of participants reporting concurrency within their primary relationship. Participants' narratives revealed significant sources and circumstances of risk, particularly multiple and concurrent sexual partnerships, violence and lack of mutual trust within relationships, as well as social ideals that may provide opportunities for effective HIV prevention. PMID- 26901066 TI - Recurring exon deletions in the HP (haptoglobin) gene contribute to lower blood cholesterol levels. AB - One of the first protein polymorphisms identified in humans involves the abundant blood protein haptoglobin. Two exons of the HP gene (encoding haptoglobin) exhibit copy number variation that affects HP protein structure and multimerization. The evolutionary origins and medical relevance of this polymorphism have been uncertain. Here we show that this variation has likely arisen from many recurring deletions, more specifically, reversions of an ancient hominin-specific duplication of these exons. Although this polymorphism has been largely invisible to genome-wide genetic studies thus far, we describe a way to analyze it by imputation from SNP haplotypes and find among 22,288 individuals that these HP exonic deletions associate with reduced LDL and total cholesterol levels. We further show that these deletions, and a SNP that affects HP expression, appear to drive the strong association of cholesterol levels with SNPs near HP. Recurring exonic deletions in HP likely enhance human health by lowering cholesterol levels in the blood. PMID- 26901065 TI - A multiple-phenotype imputation method for genetic studies. AB - Genetic association studies have yielded a wealth of biological discoveries. However, these studies have mostly analyzed one trait and one SNP at a time, thus failing to capture the underlying complexity of the data sets. Joint genotype phenotype analyses of complex, high-dimensional data sets represent an important way to move beyond simple genome-wide association studies (GWAS) with great potential. The move to high-dimensional phenotypes will raise many new statistical problems. Here we address the central issue of missing phenotypes in studies with any level of relatedness between samples. We propose a multiple phenotype mixed model and use a computationally efficient variational Bayesian algorithm to fit the model. On a variety of simulated and real data sets from a range of organisms and trait types, we show that our method outperforms existing state-of-the-art methods from the statistics and machine learning literature and can boost signals of association. PMID- 26901067 TI - Frequent somatic CDH1 loss-of-function mutations in plasmacytoid variant bladder cancer. AB - Plasmacytoid bladder cancer is an aggressive histologic variant with a high risk of disease-specific mortality. Using whole-exome and targeted sequencing, we find that truncating somatic alterations in the CDH1 gene occur in 84% of plasmacytoid carcinomas and are specific to this histologic variant. Consistent with the aggressive clinical behavior of plasmacytoid carcinomas, which frequently recur locally, CRISPR/Cas9-mediated knockout of CDH1 in bladder cancer cells enhanced cell migration. PMID- 26901069 TI - RNA-Seq Reveals the Angiogenesis Diversity between the Fetal and Adults Bone Mesenchyme Stem Cell. AB - In this research, we used RNA sequencing (RNA-seq) to analyze 23 single cell samples and 2 bulk cells sample from human adult bone mesenchyme stem cell line and human fetal bone mesenchyme stem cell line. The results from the research demonstrated that there were big differences between two cell lines. Adult bone mesenchyme stem cell lines showed a strong trend on the blood vessel differentiation and cell motion, 48/49 vascular related differential expressed genes showed higher expression in adult bone mesenchyme stem cell lines (Abmsc) than fetal bone mesenchyme stem cell lines (Fbmsc). 96/106 cell motion related genes showed the same tendency. Further analysis showed that genes like ANGPT1, VEGFA, FGF2, PDGFB and PDGFRA showed higher expression in Abmsc. This work showed cell heterogeneity between human adult bone mesenchyme stem cell line and human fetal bone mesenchyme stem cell line. Also the work may give an indication that Abmsc had a better potency than Fbmsc in the future vascular related application. PMID- 26901070 TI - Characterization of the Photophysical, Thermodynamic, and Structural Properties of the Terbium(III)-DREAM Complex. AB - DREAM (also known as K(+) channel interacting protein 3 and calsenilin) is a calcium binding protein and an active modulator of KV4 channels in neuronal cells as well as a novel Ca(2+)-regulated transcriptional modulator. DREAM has also been associated with the regulation of Alzheimer's disease through the prevention of presenilin-2 fragmentation. Many interactions of DREAM with its binding partners (Kv4, calmodulin, DNA, and drugs) have been shown to be dependent on calcium. Therefore, understanding the structural changes induced by binding of metals to DREAM is essential for elucidating the mechanism of signal transduction and biological activity of this protein. Here, we show that the fluorescence emission and excitation spectra of the calcium luminescent analogue, Tb(3+), are enhanced upon binding to the EF-hands of DREAM due to a mechanism of energy transfer between Trp and Tb(3+). We also observe that unlike Tb(3+)-bound calmodulin, the luminescence lifetime of terbium bound to DREAM decays as a complex multiexponential (tauaverage ~ 1.8 ms) that is sensitive to perturbation of the protein structure and drug (NS5806) binding. Using isothermal calorimetry, we have determined that Tb(3+) binds to at least three sites with high affinity (Kd = 1.8 MUM in the presence of Ca(2+)) and displaces bound Ca(2+) through an entropically driven mechanism (DeltaH ~ 12 kcal mol(-1), and TDeltaS ~ 22 kcal mol(-1)). Furthermore, the hydrophobic probe 1,8-ANS shows that Tb(3+), like Ca(2+), triggers the exposure of a hydrophobic surface on DREAM, which modulates ligand binding. Analogous to Ca(2+) binding, Tb(3+) binding also induces the dimerization of DREAM. Secondary structural analyses using far-UV circular dichroism and trapped ion mobility spectrometry-mass spectrometry reveal that replacement of Ca(2+) with Tb(3+) preserves the folding state with minimal changes to the overall structure of DREAM. These findings pave the way for further investigation of the metal binding properties of DREAM using lanthanides as well as the study of DREAM-protein complexes by lanthanide resonance energy transfer or nuclear magnetic resonance. PMID- 26901071 TI - Not flavone-8-acetic acid (FAA) but its murine metabolite 6-OH-FAA exhibits remarkable antivascular activities in vitro. AB - Flavone-8-acetic acid (FAA) has been proved to be a potent vascular-disrupting agent in mice. Unfortunately, FAA did not produce any anticancer activity in clinical trials. Previously, we had reported that FAA is metabolized by mouse microsomes into six metabolites, whereas it was poorly metabolized by human microsomes, with fewer metabolites formed in lesser amounts. Especially, 6-OH-FAA was not formed by human microsomes. In this work, two major available metabolites, 4'-OH-FAA and 6-OH-FAA, were tested and compared with the parent compound FAA for their potential antivascular activities in vitro. The ability of the products to induce morphological changes, disrupt preformed capillaries of EA.hy926 endothelial cells and inhibit tubulin polymerization in vitro was assessed. The action mechanism was determined using the RhoA and Rac1 inhibitors. At 25 ug/ml, 6-OH-FAA induced morphological changes and membrane blebbing, whereas 300 ug/ml of FAA and 4'-OH-FAA slightly changed the morphology without inducing membrane blebbing. At 300 ug/ml, 6-OH-FAA produced morphological changes that were 2.1-6.9-fold greater than that produced by FAA and 4'-OH-FAA, an effect that was consistent with its much greater inhibitory effect on tubulin polymerization compared with FAA and 4'-OH-FAA. 6-OH-FAA significantly disrupted the EA.hy926 cell capillaries. 6-OH-FAA activities were prevented in EA.hy926 cells pretreated with RhoA, but not Rac1, inhibitor. In this short communication we report for the first time that, in vitro, 6-OH-FAA, a mouse-specific FAA metabolite, exhibits significantly stronger antivascular activities compared with FAA and 4'-OH-FAA, which are mediated through the RhoA kinase pathway. PMID- 26901068 TI - The genome sequences of Arachis duranensis and Arachis ipaensis, the diploid ancestors of cultivated peanut. AB - Cultivated peanut (Arachis hypogaea) is an allotetraploid with closely related subgenomes of a total size of ~2.7 Gb. This makes the assembly of chromosomal pseudomolecules very challenging. As a foundation to understanding the genome of cultivated peanut, we report the genome sequences of its diploid ancestors (Arachis duranensis and Arachis ipaensis). We show that these genomes are similar to cultivated peanut's A and B subgenomes and use them to identify candidate disease resistance genes, to guide tetraploid transcript assemblies and to detect genetic exchange between cultivated peanut's subgenomes. On the basis of remarkably high DNA identity of the A. ipaensis genome and the B subgenome of cultivated peanut and biogeographic evidence, we conclude that A. ipaensis may be a direct descendant of the same population that contributed the B subgenome to cultivated peanut. PMID- 26901072 TI - The prognostic significance of bacterial DNA in patients with decompensated cirrhosis and suspected infection. AB - BACKGROUND & AIMS: Circulating and peritoneal fragments of microbial DNA (bactDNA) are evidence for bacterial translocation in decompensated cirrhosis and may serve as a rational approach for antibiotic therapy when infection is suspected. METHODS: Prospective multicenter study to investigate whether identification of bactDNA from blood or ascitic fluid (AF) by multiplex polymerase chain reaction (PCR) is associated with increased 90-day mortality in 218 patients with cirrhosis and signs of infection. RESULTS: BactDNA in either compartment was detected in 134 (61%) patients, comprising 54 with bactDNA in blood and AF, 48 with AF bactDNA only, and 32 with blood bactDNA only. BactDNA was associated with spontaneous bacterial peritonitis and blood stream infections (SBP/BSI), acute-on-chronic liver failure (ACLF), encephalopathy and markers of inflammation. The prevalence of bactDNA in patients with proven SBP/BSI (36/49; 73%) was similar to that in patients with sterile ACLF (37/52; 71%). Actuarial 90 day survival was 56 +/- 5% in the absence of bactDNA in both compartments and did not differ if bactDNA was detected in blood only (63 +/- 9%), AF only (63 +/- 7%), or in blood and AF (52 +/- 7%). Predictors of 90-day mortality were SBP (HR = 3.10; 95% CI: 1.90-5.06), BSI (HR = 4.94; 95% CI: 2.71-9.02), and ACLF (HR = 2.20; 95% CI: 1.44-3.35). The detection of resistance genes in blood or AF in the absence of SBP/BSI (n = 11) was associated with poor 1-year survival (HR = 2.35; 95% CI: 1.03-5.35). CONCLUSIONS: BactDNA in sterile body fluids did not indicate increased mortality in cirrhotic patients with suspected infection. Using multiplex PCR for risk stratification cannot be recommended in these patients. PMID- 26901073 TI - Spatial distribution of dust-bound trace elements in Pakistan and their implications for human exposure. AB - This study aims to assess the spatial patterns of selected dust-borne trace elements alongside the river Indus Pakistan, their relation with anthropogenic and natural sources, and the potential risk posed to human health. The studied elements were found in descending concentrations: Mn, Zn, Pb, Cu, Ni, Cr, Co, and Cd. The Index of Geo-accumulation indicated that pollution of trace metals were higher in lower Indus plains than on mountain areas. In general, the toxic elements Cr, Mn, Co and Ni exhibited altitudinal trends (P < 0.05). The few exceptions to this trend were the higher values for all studied elements from the northern wet mountainous zone (low lying Himalaya). Spatial PCA/FA highlighted that the sources of different trace elements were zone specific, thus pointing to both geological influences and anthropogenic activities. The Hazard Index for Co and for Mn in children exceeded the value of 1 only in the riverine delta zone and in the southern low lying zone, whereas the Hazard Index for Pb was above the bench mark for both children and adults (with few exceptions) in all regions, thus indicating potential non-carcinogenic health risks. These results will contribute towards the environmental management of trace metal(s) with potential risk for human health throughout Pakistan. PMID- 26901074 TI - Changes in atmospheric concentrations of polycyclic aromatic hydrocarbons and polychlorinated biphenyls between the 1990s and 2010s in an Australian city and the role of bushfires as a source. AB - Over recent decades, efforts have been made to reduce human exposure to atmospheric pollutants including polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) through emission control and abatement. Along with the potential changes in their concentrations resulting from these efforts, profiles of emission sources may have also changed over such extended timeframes. However relevant data are quite limited in the Southern Hemisphere. We revisited two sampling sites in an Australian city, where the concentration data in 1994/5 for atmospheric PAHs and PCBs were available. Monthly air samples from July 2013 to June 2014 at the two sites were collected and analysed for these compounds, using similar protocols to the original study. A prominent seasonal pattern was observed for PAHs with elevated concentrations in cooler months whereas PCB levels showed little seasonal variation. Compared to two decades ago, atmospheric concentrations of ?13 PAHs (gaseous + particle-associated) in this city have decreased by approximately one order of magnitude and the apparent halving time (t1/2) was estimated as 6.2 +/- 0.56 years. ?6iPCBs concentrations (median value; gaseous + particle-associated) have decreased by 80% with an estimated t1/2 of 11 +/- 2.9 years. These trends and values are similar to those reported for comparable sites in the Northern Hemisphere. To characterise emission source profiles, samples were also collected from a bushfire event and within a vehicular tunnel. Emissions from bushfires are suggested to be an important contributor to the current atmospheric concentrations of PAHs in this city. This contribution is more important in cooler months, i.e. June, July and August, and its importance may have increased over the last two decades. PMID- 26901075 TI - Selenium inhibits sulfate-mediated methylmercury production in rice paddy soil. AB - There is increasing interest in understanding factors controlling methylmercury (MeHg) production in mercury-contaminated rice paddy soil. Sulfate has been reported to affect MeHg biogeochemistry under anoxic conditions, and recent studies revealed that selenium (Se) could evidently reduce MeHg production in paddy soil. However, the controls of sulfate and Se on net MeHg production in paddy soil under fluctuating redox conditions remain largely unknown. Microcosm experiments were conducted to explore the effects of sulfate and Se on net MeHg production in rice paddy soil. Soil was added with 0-960 mg/kg sulfate, in the presence or absence of 3.0 mg/kg selenium (selenite or selenate), and incubated under anoxic (40 days) or suboxic conditions (5 days), simulating fluctuating redox conditions in rice paddy field. Sulfate addition moderately affected soil MeHg concentrations under anoxic conditions, while reoxidation resulted in evidently higher (18-40%) MeHg levels in sulfate amended soils than the control. The observed changes in net MeHg production were related to dynamics of sulfate and iron. However, Se could inhibit sulfate-mediated MeHg production in the soils: Se addition largely reduced net MeHg production in the soils (23-86%, compared to the control), despite of sulfate addition. Similarly, results of the pot experiments (i.e., rice cultivation in amended soils) indicated that soil MeHg levels were rather comparable in Se-amended soils during rice growth period, irrespective of added sulfate doses. The more important role of Se than sulfate in controlling MeHg production was explained by the formation of HgSe nanoparticles irrespective of the presence of sulfate, confirmed by TEM-EDX and XANES analysis. Our findings regarding the effects of sulfate and Se on net MeHg production in rice paddy soil together with the mechanistic explanation of the processes advance our understanding of MeHg dynamics and risk in soil-rice systems. PMID- 26901076 TI - Intestinal Graft Failure: Should We Perform the Allograft Enterectomy Before or With Retransplantation? AB - BACKGROUND: Intestinal graft dysfunction is sometimes irreversible and requires allograft enterectomy with or without retransplantation. There is no comprehensive assessment of allograft enterectomy regarding indications and outcomes. The aim of this study was to evaluate management of patients with intestinal graft failure with special reference to indications and outcomes of allograft enterectomy and the procedure's validity as a bridge to retransplantation. METHODS: Graft and patient survivals, reason for graft failure, and rejection episodes were evaluated in 221 intestinal recipients (primary transplantation [n = 201], retransplantation [n = 20]). Indications, surgical factors, and outcomes of allograft enterectomy were investigated. RESULTS: Reasons for isolated enterectomy included systemic infection in 11, gastrointestinal bleeding in 1, and severe electrolyte imbalance in 1, all of which were associated with rejection. One isolated intestinal transplantation patient underwent isolated enterectomy due to cytomegalovirus enteritis. One multivisceral transplantation patient underwent isolated allograft enterectomy due to bowel necrosis. Of these 15 patients, 3 died from persistent infection postoperatively, whereas 8 underwent retransplantation with median interval of 74 days (42-252 days). Allosensitization occurred between isolated enterectomy and retransplantation in 2, one of whom lost the second graft due to rejection. Simultaneous allograft enterectomy and retransplantation was performed in 3 isolated intestinal transplantation and 9 multivisceral transplantation patients. Patient survival after retransplantation was similar between patients who underwent isolated allograft enterectomy and those who did simultaneous enterectomy with retransplantation (P = 0.82). CONCLUSIONS: In cases of irreversible intestinal graft dysfunction, isolated allograft enterectomy successfully provides recovery from comorbidities as a lifesaving procedure and does not compromise outcomes of retransplantation. PMID- 26901077 TI - HLA Matching for Renal Transplantation: The Last Word? PMID- 26901078 TI - The Risk of Transplant Failure With HLA Mismatch in First Adult Kidney Allografts From Deceased Donors. AB - BACKGROUND: Since the beginning of the technology, there has been active debate about the role of human leucocyte antigen (HLA) matching in kidney allograft survival. Recent studies have reported diminishing importance of HLA matching, which have, in turn, been challenged by reports that suggest the continuing importance of these loci. Given the controversies, we examined the effect of HLA compatibility on kidney allograft survival by studying all first adult kidney transplants in the United States from a deceased donor. METHODS: Using the United Network for Organ Sharing data, we identified first deceased donor kidney transplants between October 1, 1987, and December 31, 2013. Recipients were classified by their number of HLA mismatches. Cox multivariate regression analyses adjusting for recipient and donor transplant characteristics were performed to determine the impact of HLA compatibility on kidney allograft survival. RESULTS: Study cohort included 189 141 first adult kidney alone transplants, with a total of 994 558 years of kidney allograft follow-up time. Analyses adjusted for recipient and donor characteristics demonstrated a 13% higher risk (hazard ratio, 1.13; 95% confidence interval, 1.06-1.21) with 1 mismatch and a 64% higher risk (hazard ratio, 1.64, 95% confidence interval, 1.56 1.73) with 6 mismatches. Dividing the mismatch categories into 27 ordered permutations, and testing their 57 within mismatch category differences, demonstrated that all but 1 were equal, independent of locus. CONCLUSIONS: A significant linear relationship of hazard ratios was associated with HLA mismatch and affects allograft survival even during the recent periods of increasing success in renal transplantation. PMID- 26901079 TI - Rejection of the Renal Allograft in the Absence of Demonstrable Antibody and Complement. AB - BACKGROUND: Recent literature has stressed the prominent role of antibodies in graft loss. This study was designed to assess a growing perception that T cell mediated rejection (TCMR) is no longer clinically relevant. METHODS: Five hundred forty-five renal allograft recipients over a 3-year period were screened for biopsies with: (a) TCMR including borderline change (BL), (b) negative complement protein C4 degradation fragment, and (c) absence of donor-specific antibody at time of transplant, within 30 days of the biopsy, and up to 4 measurements at later time points. RESULTS: These stringent requirements identified 28 "pure" cases of late TCMR/BL. Low-grade glomerulitis, peritubular capillaritis, or chronic transplant glomerulopathy were found in 9/28 (32%) biopsies. Serum creatinine showed complete short-term remission in 7/10 (70%) BL and 9/18 (50%) TCMR patients 1 month postbiopsy. Yet, both treated and untreated patients demonstrated further decline in graft function as assessed by serum creatinine and estimated glomerular filtration rate. CONCLUSIONS: Late TCMR seen in 7.9% of biopsies can contribute to significant deterioration of graft function in patients in whom the dominant contribution of antibody-mediated injury has been reasonably excluded. Our data also reinforce existing literature showing that microvascular lesions do not have absolute specificity for a diagnosis of antibody-mediated rejection. PMID- 26901080 TI - Overall Graft Loss Versus Death-Censored Graft Loss: Unmasking the Magnitude of Racial Disparities in Outcomes Among US Kidney Transplant Recipients. AB - BACKGROUND: Black kidney transplant recipients experience disproportionately high rates of graft loss. This disparity has persisted for 40 years, and improvements may be impeded based on the current public reporting of overall graft loss by US regulatory organizations for transplantation. METHODS: Longitudinal cohort study of kidney transplant recipients using a data set created by linking Veterans Affairs and US Renal Data System information, including 4918 veterans transplanted between January 2001 and December 2007, with follow-up through December 2010. Multivariable analysis was conducted using 2-stage joint modeling of random and fixed effects of longitudinal data (linear mixed model) with time to event outcomes (Cox regression). RESULTS: Three thousand three hundred six non Hispanic whites (67%) were compared with 1612 non-Hispanic black (33%) recipients with 6.0 +/- 2.2 years of follow-up. In the unadjusted analysis, black recipients were significantly more likely to have overall graft loss (hazard ratio [HR], 1.19; 95% confidence interval [95% CI], 1.07-1.33), death-censored graft loss (HR, 1.67; 95% CI, 1.45-1.92), and lower mortality (HR, 0.83; 95% CI, 0.72-0.96). In fully adjusted models, only death-censored graft loss remained significant (HR, 1.38; 95% CI, 1.12-1.71; overall graft loss [HR, 1.08; 95% CI, 0.91-1.28]; mortality [HR, 0.84; 95% CI, 0.67-1.06]). A composite definition of graft loss reduced the magnitude of disparities in blacks by 22%. CONCLUSIONS: Non-Hispanic black kidney transplant recipients experience a substantial disparity in graft loss, but not mortality. This study of US data provides evidence to suggest that researchers should focus on using death-censored graft loss as the primary outcome of interest to facilitate a better understanding of racial disparities in kidney transplantation. PMID- 26901081 TI - Urinary Calprotectin Differentiates Between Prerenal and Intrinsic Acute Renal Allograft Failure. AB - BACKGROUND: Urinary calprotectin has recently been identified as a promising biomarker for the differentiation between prerenal and intrinsic acute kidney injury (AKI) in the nontransplant population. The present study investigates whether calprotectin is able to differentiate between these 2 entities in transplant recipients as well. METHODS: Urinary calprotectin was assessed by enzyme-linked immunosorbent assay in 328 subjects including 125 cases of intrinsic acute allograft failure, 27 prerenal graft failures, 118 patients with stable graft function, and 58 healthy controls. Acute graft failure was defined as AKI stages 1 to 3 (Acute Kidney Injury Network criteria), exclusion criteria were obstructive uropathy, urothelial carcinoma, and metastatic cancer. The clinical differentiation of prerenal and intrinsic graft failure was performed either by biopsy or by a clinical algorithm including response to fluid repletion, history, physical examination, and urine dipstick examination. RESULTS: Reasons for intrinsic graft failure comprised rejection, acute tubular necrosis, urinary tract infection/pyelonephritis, viral nephritis, and interstitial nephritis. Calprotectin concentrations of patients with stable graft function (50.4 ng/mL) were comparable to healthy controls (54.8 ng/mL, P = 0.70) and prerenal graft failure (53.8 ng/mL, P = 0.62). Median urinary calprotectin was 36 times higher in intrinsic AKI (1955 ng/mL) than in prerenal AKI (P < 0.001). Receiver-operating characteristic curve analysis revealed a high accuracy of calprotectin (area under the curve, 0.94) in the differentiation of intrinsic versus prerenal AKI. A cutoff level of 134.5 ng/mL provided a sensitivity of 90.4% and a specificity of 74.1%. Immunohistochemical stainings for calprotectin in renal allograft biopsy specimens confirmed the serological results. CONCLUSIONS: Urinary calprotectin is a promising biomarker for the differentiation of prerenal and intrinsic acute renal allograft failure. PMID- 26901082 TI - A bifactor model of the Beck Depression Inventory and its association with medical prognosis after myocardial infarction. AB - OBJECTIVES: Evidence suggests that depression is associated with adverse outcomes in patients with myocardial infarction (MI). Some of the symptoms of depression may also be symptoms of somatic illness and these may confound the association between depression and prognosis. We investigated whether depression following MI is associated with medical prognosis independent of these somatic symptoms. METHOD: The database of an individual patient data meta-analysis was used. Endpoints were all-cause mortality and cardiovascular events. Nine studies were included. Bifactor factor analysis included 13,100 participants and 7,595 participants were included in survival models. Dimensions were generated from the Beck Depression Inventory using factor analyses. The prognostic association was assessed using mixed-effects Cox regression analysis. RESULTS: A bifactor model, consisting of a general factor and 2 general depression-free subgroup factors (a somatic/affective and a cognitive/affective), provided the best fit. There was a significant association between the general depression factor and all-cause mortality (hazard ratio [HR] = 1.25; 95% confidence interval [CI] [1.17, 1.34], p < .001) and cardiovascular events (HR = 1.18; 95% CI [1.13, 1.23], p < .001). After adjustment for demographics, measures of cardiac disease severity, and health-related variables, the association between the general depression factor and all-cause mortality (HR = 1.14; 95% CI [1.04, 1.25], p = .003) and cardiovascular events (HR = 1.16; 95% CI [1.10, 1.23], p = .014) attenuated. Additionally, the general depression-free somatic/affective factor was significantly associated with the endpoints, while the general depression-free cognitive/affective was not. CONCLUSIONS: A general depression factor is associated with adverse medical prognosis following MI independent of somatic/affective symptoms that may be partly attributable to somatic illness. (PsycINFO Database Record PMID- 26901083 TI - The impact of item order and sex on self-report of pain intensity in children. AB - OBJECTIVE: When questionnaires are used for pain assessment, the order effect must be taken into consideration; that is, whether the answer to a pain item is influenced by answers given to previous items. This study aimed to evaluate possible order effects in children and adolescents when answering pain items. Furthermore, the possible influence of sex on order effects was analyzed. METHOD: Three pain items (worst, at movement, and at rest) were given in 6 different orders. Two hundred and 46 postoperative hospitalized children and adolescents (age range of 11-18 years, mean of 14.4 years; female: 41%, duration of surgery range of 2-274 min) participated in this study. Each item order was answered by 40-43 children and adolescents. RESULTS: While there were no general order effects, we observed a sex-specific order effect. The position of pain at rest (p = .034) and pain on movement (p = .036) items had different influences on worst pain values in female patients compared to male patients. A sex-specific influence on pain at rest values was only caused by the position of pain on movement items (p = .036). CONCLUSION: The fact that male and female pediatric patients are differently influenced by the order of pain items has to be considered in planning a questionnaire. As more specific items (pain on movement) are less influenced by the item order effect, they should be preferred. PMID- 26901084 TI - A rapidly progressive defective spermatogenesis in a Mexican family affected by spino-bulbar muscular atrophy. AB - Spino-bulbar muscular atrophy (SBMA) is an X-linked recessive adult progressive disorder affecting motor neurons. It is caused by a poly-glutamine tract expansion in the androgen receptor (AR) which generates protein aggregates that cannot be processed by proteasomes. A secondary mild androgen resistance is developed by AR dysfunction and patients present endocrine abnormalities including gynecomastia and poor function of testosterone in tissues; however, normally they are fertile. In this report we describe a Mexican family with three affected brothers with primary infertility caused by a progressive impairment of spermatogenesis leading to azoospermia before 40 years of age. They presented common features associated to patients affected by SMBA, such as gynecomastia, high level of CPK, muscle cramps, fasciculations, muscle wastage, and impaired swallowing. Two intracytoplasmic sperm injection (ICSI) cycles were performed in one of the patients resulting in fertilization failure. Molecular analysis of AR gene exon 1 revealed 54 CAG repeats in DNA extracted from leukocytes in affected patients and 22 repeats in the fertile non-affected brother. Severe impaired spermatogenesis of rapid progression has not been associated before to SBMA. This is the first report of assisted reproduction techniques indicated by male infertility in patients with this rare disorder. Further studies are required to confirm the unusual result of intracytoplasmic sperm injection cycles. We discuss the implications and possible pathogenesis of these unique features of SBMA in this family. PMID- 26901085 TI - Chemical Diversity, Origin, and Analysis of Phycotoxins. AB - Microalgae, particularly those from the lineage Dinoflagellata, are very well known for their ability to produce phycotoxins that may accumulate in the marine food chain and eventually cause poisoning in humans. This includes toxins accumulating in shellfish, such as saxitoxin, okadaic acid, yessotoxins, azaspiracids, brevetoxins, and pinnatoxins. Other toxins, such as ciguatoxins and maitotoxins, accumulate in fish, where, as is the case for the latter compounds, they can be metabolized to even more toxic metabolites. On the other hand, much less is known about the chemical nature of compounds that are toxic to fish, the so-called ichthyotoxins. Despite numerous reports of algal blooms causing massive fish kills worldwide, only a few types of compounds, such as the karlotoxins, have been proven to be true ichthyotoxins. This review will highlight marine microalgae as the source of some of the most complex natural compounds known to mankind, with chemical structures that show no resemblance to what has been characterized from plants, fungi, or bacteria. In addition, it will summarize algal species known to be related to fish-killing blooms, but from which ichthyotoxins are yet to be characterized. PMID- 26901086 TI - Brugada Phenocopy as a Dynamic Electrocardiographic Pattern during Acute Anterior Myocardial Infarction. AB - Brugada phenocopies represent some unusual clinical cases with identical characteristics to Brugada syndrome (BrS) elicited by various clinical circumstances. We report the case of a woman exhibiting "Brugada Phenocopy" during an acute anterior myocardial infarction, highlighting differential diagnosis with true BrS and discussing possible mechanisms underlying its dynamic ECG pattern. PMID- 26901087 TI - Symptomatic giant peritoneal loose body in the pelvic cavity: A case report. AB - INTRODUCTION: Giant peritoneal loose bodies (gPLB) occur rarely and therefore only few have been described. Often they are found incidentally and have no clinical relevance, whereas symptomatic forms may require surgical removal. PRESENTATION OF CASE: We report the case of a male patient suffering from abdominal discomfort with alternating localizations for several years, actually presenting with a proctitis. With elevated inflammatory markers, a conspicuous resistance in the lower abdomen and in order to evaluate further affection of the colon, an abdominal CT-scan was performed. It revealed a spherical mass in the lesser pelvis. A colonoscopy confirmed the proctitis, showing no further pathologies. Due to the symptoms and the uncertain entity of the mass, a diagnostic laparoscopy was performed and a boiled egg-like structure (diameter 5.2cm) was removed. The patient recovered well and was free of symptoms. DISCUSSION: The patient had two potential reasons for his symptoms, one of them being a suspected leftover foreign body years after an appendectomy. The proctitis was treated conservatively but without complete remission of the abdominal discomfort. Therefore, a diagnostic laparoscopy was performed and the mass turned out to be a gPLB. CONCLUSION: To obtain a fast diagnosis and to perform an adequate conservative or surgical therapy, the knowledge about the rare entity of a gPLB is necessary. An exact anamnesis, clinical examination and the knowledge about the diagnostic values of radiological and endoscopic investigations are crucial. PMID- 26901088 TI - Evaluation of military helmets and roof padding on head injury potential from vertical impacts. AB - OBJECTIVE: Soldiers in military vehicles subjected to underbelly blasts can sustain traumatic head and neck injuries due to a head impact with the roof. The severity of head and neck trauma can be influenced by the amount of head clearance available to the occupant as well as factors such as wearing a military helmet or the presence of padding on the interior roof. The aim of the current study was to examine the interaction between a Hybrid III headform, the helmet system, and the interior roof of the vehicle under vertical loading. METHODS: Using a head impact machine and a Hybrid III headform, tests were conducted on a rigid steel plate in a number of different configurations and velocities to assess helmet shell and padding performance, to evaluate different vehicle roof padding materials, and to determine the relative injury mitigating contributions of both the helmet and the roof padding. The resultant translational head acceleration was measured and the head injury criterion (HIC) was calculated for each impact. RESULTS: For impacts with a helmeted headform hitting the steel plate only, which represented a common scenario in an underbelly blast event, velocities of <=6 m/s resulted in HIC values below the FMVSS 201U threshold of 1,000, and a velocity of 7 m/s resulted in HIC values well over the threshold. Roof padding was found to reduce the peak translational head acceleration and the HIC, with rigid IMPAXX foams performing better than semirigid ethylene vinyl acetate (EVA) foam. However, the head injury potential was reduced considerably more by wearing a helmet than by the addition of roof padding. CONCLUSIONS: The results of this study provide initial quantitative findings that provide a better understanding of helmet-roof interactions in vertical impacts and the contributions of the military helmet and roof padding to mitigating head injury potential. Findings from this study will be used to inform further testing with the future aim of developing a new minimum head clearance standard for occupants of light armored vehicles. PMID- 26901089 TI - A novel Pseudomonas gessardii strain LZ-E simultaneously degrades naphthalene and reduces hexavalent chromium. AB - Combined pollutants with polycyclic aromatic hydrocarbons (PAHs) and heavy metals have been identified as toxic and unmanageable contaminates. In this work, Pseudomonas gessardii strain LZ-E isolated from wastewater discharge site of a petrochemical company degrades naphthalene and reduces Cr(VI) simultaneously. 95% of 10mgL(-1) Cr(VI) was reduced to Cr(III) while 77% of 800mgL(-1) naphthalene was degraded when strain LZ-E was incubated in BH medium for 48h. Furthermore, naphthalene promotes Cr(VI) reduction in strain LZ-E as catechol and phthalic acid produced in naphthalene degradation are able to reduce Cr(VI) abiotically. An aerated bioreactor system was setup to test strain LZ-E's remediation ability. Strain LZ-E continuously remediated naphthalene and Cr(VI) at rates of 15mgL( 1)h(-1) and 0.20mgL(-1)h(-1) of 800mgL(-1) naphthalene and 10mgL(-1) Cr(VI) addition with eight batches in 16days. In summary, strain LZ-E is a potential applicant for combined pollution remediation. PMID- 26901090 TI - Thermochemical conversion of biomass in smouldering combustion across scales: The roles of heterogeneous kinetics, oxygen and transport phenomena. AB - The thermochemical conversion of biomass in smouldering combustion is investigated here by combining experiments and modeling at two scales: matter (1mg) and bench (100g) scales. Emphasis is put on the effect of oxygen (0 33vol.%) and oxidation reactions because these are poorly studied in the literature in comparison to pyrolysis. The results are obtained for peat as a representative biomass for which there is high-quality experimental data published previously. Three kinetic schemes are explored, including various steps of drying, pyrolysis and oxidation. The kinetic parameters are found using the Kissinger-Genetic Algorithm method, and then implemented in a one-dimensional model of heat and mass transfer. The predictions are validated with thermogravimetric and bench-scale experiments and then analyzed to unravel the role of heterogeneous reaction. This is the first time that the influence of oxygen on biomass smouldering is explained in terms of both chemistry and transport phenomena across scales. PMID- 26901091 TI - Overexpression of beta-Klotho in Adipose Tissue Sensitizes Male Mice to Endogenous FGF21 and Provides Protection From Diet-Induced Obesity. AB - The endocrine hormone fibroblast growth factor 21 (FGF21) is induced in the adaptive response to nutrient deprivation, where it serves to regulate the integrated response to fasting via its primary receptor complex, FGF receptor 1 coupled with the cofactor beta-klotho (KLB) in target tissues. Curiously, endogenous FGF21 levels are also elevated in preclinical models of obesity and in obese/diabetic individuals. In addition to higher FGF21 levels, reduced KLB expression in liver and adipose tissue has been noted in these same individuals, suggesting that obesity may represent an FGF21 resistant state. To explore the contribution of tissue-specific KLB levels to endogenous FGF21 activity, in both fasting and high-fat diet feeding conditions, we generated animals overexpressing KLB in liver (LKLBOE) or adipose (ATKLBOE). Supportive of tissue-specific partitioning of FGF21 action, after chronic high-fat feeding, ATKLBOE mice gained significantly less weight than WT. Reduced weight gain was associated with elevated caloric expenditure, accompanied by a reduced respiratory exchange ratio and lower plasma free fatty acids levels, suggestive of augmented lipid metabolism. In contrast, LKLBOE had no effect on body weight but did reduce plasma cholesterol. The metabolic response to fasting was enhanced in LKLBOE mice, evidenced by increased ketone production, whereas no changes in this were noted in ATKLBOE mice. Taken together, these data provide further support that specific effects of FGF21 are mediated via engagement of distinct target organs. Furthermore, enhancing KLB expression in adipose may sensitize to endogenous FGF21, thus representing a novel strategy to combat metabolic disease. PMID- 26901097 TI - Cortical and subcortical vascular hypointensity on T2* weighted imaging in moyamoya disease. AB - OBJECTIVES: Decreased cortical and subcortical vascular signals in gradient echo T2* weighted imaging have been reported in acute stroke due to major artery occlusion. The purpose of this study was to evaluate this cortical and subcortical vascular hypointensity (CSVH) in patients with moyamoya disease. METHODS: Subjects were 20 consecutive patients with moyamoya disease. The numbers of CSVH in each hemisphere were counted and the numbers were compared between patients with moyamoya disease and controls. The distribution of CSVH, clinical features of cases exhibiting large numbers of CSVH and post-operative changes were analysed. RESULTS: Patients with moyamoya disease had significantly more CSVH in the middle cerebral artery territory (p < 0.001) and the anterior cerebral artery territory (p < 0.001) compared with controls. The number of CSVH was correlated significantly with regional cerebral blood flow, as shown through simple regression analysis (R = 0.461, p = 0.006), and the numbers of CSVH were significantly higher in patients with higher magnetic resonance angiography scores (p = 0.017). A given patient's total number of CSVH per hemisphere was significantly decreased after surgery (p = 0.018). CONCLUSION: CSVH on T2* WI may be a useful tool for diagnosing and evaluating the extent of moyamoya disease. Our small series study shows that revascularization surgery can decrease the number of CSVH. PMID- 26901093 TI - Diurnal Corticosterone Presence and Phase Modulate Clock Gene Expression in the Male Rat Prefrontal Cortex. AB - Mood disorders are associated with dysregulation of prefrontal cortex (PFC) function, circadian rhythms, and diurnal glucocorticoid (corticosterone [CORT]) circulation. Entrainment of clock gene expression in some peripheral tissues depends on CORT. In this study, we characterized over the course of the day the mRNA expression pattern of the core clock genes Per1, Per2, and Bmal1 in the male rat PFC and suprachiasmatic nucleus (SCN) under different diurnal CORT conditions. In experiment 1, rats were left adrenal-intact (sham) or were adrenalectomized (ADX) followed by 10 daily antiphasic (opposite time of day of the endogenous CORT peak) ip injections of either vehicle or 2.5 mg/kg CORT. In experiment 2, all rats received ADX surgery followed by 13 daily injections of vehicle or CORT either antiphasic or in-phase with the endogenous CORT peak. In sham rats clock gene mRNA levels displayed a diurnal pattern of expression in the PFC and the SCN, but the phase differed between the 2 structures. ADX substantially altered clock gene expression patterns in the PFC. This alteration was normalized by in-phase CORT treatment, whereas antiphasic CORT treatment appears to have eliminated a diurnal pattern (Per1 and Bmal1) or dampened/inverted its phase (Per2). There was very little effect of CORT condition on clock gene expression in the SCN. These experiments suggest that an important component of glucocorticoid circadian physiology entails CORT regulation of the molecular clock in the PFC. Consequently, they also point to a possible mechanism that contributes to PFC disrupted function in disorders associated with abnormal CORT circulation. PMID- 26901092 TI - Increased Gs Signaling in Osteoblasts Reduces Bone Marrow and Whole-Body Adiposity in Male Mice. AB - Bone is increasingly recognized as an endocrine organ that can regulate systemic hormones and metabolism through secreted factors. Although bone loss and increased adiposity appear to be linked clinically, whether conditions of increased bone formation can also change systemic metabolism remains unclear. In this study, we examined how increased osteogenesis affects metabolism by using an engineered G protein-coupled receptor, Rs1, to activate Gs signaling in osteoblastic cells in ColI(2.3)(+)/Rs1(+) transgenic mice. We previously showed that these mice have dramatically increased bone formation resembling fibrous dysplasia of the bone. We found that total body fat was significantly reduced starting at 3 weeks of age. Furthermore, ColI(2.3)(+)/Rs1(+) mice showed reduced O2 consumption and respiratory quotient measures without effects on food intake and energy expenditure. The mice had significantly decreased serum triacylglycerides, leptin, and adiponectin. Resting glucose and insulin levels were unchanged; however, glucose and insulin tolerance tests revealed increased sensitivity to insulin. The mice showed resistance to fat accumulation from a high-fat diet. Furthermore, ColI(2.3)(+)/Rs1(+) mouse bones had dramatically reduced mature adipocyte differentiation, increased Wingless/Int-1 (Wnt) signaling, and higher osteoblastic glucose utilization than controls. These findings suggest that osteoblasts can influence both local and peripheral adiposity in conditions of increased bone formation and suggest a role for osteoblasts in the regulation of whole-body adiposity and metabolic homeostasis. PMID- 26901094 TI - Spontaneous and CRH-Induced Excitability and Calcium Signaling in Mice Corticotrophs Involves Sodium, Calcium, and Cation-Conducting Channels. AB - Transgenic mice expressing the tdimer2(12) form of Discosoma red fluorescent protein under control of the proopiomelanocortin gene's regulatory elements are a useful model for studying corticotrophs. Using these mice, we studied the ion channels and mechanisms controlling corticotroph excitability. Corticotrophs were either quiescent or electrically active, with a 22-mV difference in the resting membrane potential (RMP) between the 2 groups. In quiescent cells, CRH depolarized the membrane, leading to initial single spiking and sustained bursting; in active cells, CRH further facilitated or inhibited electrical activity and calcium spiking, depending on the initial activity pattern and CRH concentration. The stimulatory but not inhibitory action of CRH on electrical activity was mimicked by cAMP independently of the presence or absence of arachidonic acid. Removal of bath sodium silenced spiking and hyperpolarized the majority of cells; in contrast, the removal of bath calcium did not affect RMP but reduced CRH-induced depolarization, which abolished bursting electrical activity and decreased the spiking frequency but not the amplitude of single spikes. Corticotrophs with inhibited voltage-gated sodium channels fired calcium dependent action potentials, whereas cells with inhibited L-type calcium channels fired sodium-dependent spikes; blockade of both channels abolished spiking without affecting the RMP. These results indicate that the background voltage insensitive sodium conductance influences RMP, the CRH-depolarization current is driven by a cationic conductance, and the interplay between voltage-gated sodium and calcium channels plays a critical role in determining the status and pattern of electrical activity and calcium signaling. PMID- 26901098 TI - Insights from ultrasound: Enhancing our understanding of clinical phonetics. PMID- 26901099 TI - L-Cysteine enhances nutrient absorption via a cystathionine-beta-synthase-derived H2 S pathway in rodent jejunum. AB - Hydrogen sulphide (H2 S) is generated endogenously from L-cysteine (L-Cys) by the enzymes cystathionine-beta-synthase (CBS) and cystathionine-gamma-lyase (CSE). In addition, L-Cys is commonly used as a precursor in the food and pharmaceutical industries. The aim of the present study is to determine whether L-Cys regulates intestinal nutrient transport. To that end, the presence of CBS and CSE in the jejunum epithelium was assessed by immunohistochemistry, Western blotting and the methylene blue assay. In addition, in vivo L-Cys (100 mg/kg, administered immediately after the glucose load) significantly increased blood glucose levels 30 min after the oral administration of glucose to mice. This effect of L-Cys was completely blocked by amino-oxyacetic acid (AOA; 50 mg/kg; administered at the same time as L-Cys) an inhibitor of CBS. Measurements of the short-circuit current (Isc) in the rat jejunum epithelium revealed that L-Cys (1 mmol/L; 6 min before the administration of L-alanine) enhances Na(+)-coupled L-alanine or glucose transport, and that this effect is inhibited by AOA (1 mmol/L;10 min before the administration of L-Cys), but not D,L-propargylglycine (PAG;1 mmol/L; 10 min before the administration of L-Cys), a CSE inhibitor. Notably, L-Cys evoked enhancement of nutrient transport was alleviated by glibenclamide (Gli;0.1 mmol/L; 10 min before the administration of L-Cys), a K(+) channel blocker. Together, the data indicate that L-Cys enhances jejunal nutrient transport, suggesting a new approach to future treatment of nutrition-related maladies, including a range of serious health consequences linked to undernutrition. PMID- 26901100 TI - Knock-down of a RING finger gene confers cold tolerance. AB - The plant-specific RING-domain finger proteins play important roles in plant development and stress responses. We recently identified and functionally characterized a stress-induced gene OsSRFP1 (Oryza sativa Stress-related RING Finger Protein 1) from rice. We showed evidences of the biotechnological potential of the suppression of OsSRFP1 expression in conferring cold tolerance. The increased cold tolerance of OsSRFP1 knock-down plants was associated with higher amounts of free proline and activities of antioxidant enzymes. In vitro ubiquitination assays showed that OsSRFP1 possessed E3 ubiquitin ligase activity. Some predicted interacting partners of OsSRFP1 might be the substrates for OsSRFP1-mediated protein degradation. Interestingly, OsSRFP1 had trans-activation activity, suggesting the dual roles of OsSRFP1 in post-translational and transcriptional regulations in stress responses. PMID- 26901101 TI - Chemical conversations in the gut microbiota. AB - The gut microbiota is a complex, densely populated community, home to many different species that collectively provide huge benefits for host health. Disruptions to this community, as can result from recurrent antibiotic exposure, alter the existing network of interactions between bacteria and can render this community susceptible to invading pathogens. Recent findings show that direct antagonistic and metabolic interactions play a critical role in shaping the microbiota. However, the part played by quorum sensing, a means of regulating bacterial behavior through secreted chemical signals, remains largely unknown. We have recently shown that the interspecies signal, autoinducer-2 (AI-2), can modulate the structure of the gut microbiota by using Escherichia coli to manipulate signal levels. Here, we discuss how AI-2 could influence bacterial behaviors to restore the balance between the 2 major bacteria phyla, the Bacteroidetes and Firmicutes, following antibiotic treatment. We explore how this may impact on host physiology, community susceptibility or resistance to pathogens, and the broader potential of AI-2 as a means to redress the imbalances in microbiota composition that feature in many infectious and non-infectious diseases. PMID- 26901102 TI - Comparison of Protein-Pacing Alone or With Yoga/Stretching and Resistance Training on Glycemia, Total and Regional Body Composition, and Aerobic Fitness in Overweight Women. AB - BACKGROUND: Yoga/Stretching (YS) and functional resistance (FR) training are popular exercise routines. A protein-pacing (PP) diet is a common dietary regimen. Thus, we assessed the effectiveness of a PP diet alone and in combination with either YS or FR to improve body composition and cardiometabolic health. METHODS: Twenty-seven overweight women (age = 43.2 +/- 4.6 years) were randomized into 3 groups: yoga (YS, n = 8) or resistance (FR, n = 10) training (3 days/week) in conjunction with PP diet (50% carbohydrate, 25% protein, and 25% fat) or PP diet-only (PP, n = 9) throughout 12-week study. PP maintained preexisting levels of physical activity. Body weight (BW), total (BF) and abdominal (ABF) body fat, waist circumference (WC), plasma biomarkers, and aerobic fitness (VO2) were measured at baseline and 12 weeks. RESULTS: WC and total cholesterol improved in all groups, whereas glycemia tended to improve (P = .06) in S. BF, ABF, and VO2 increased significantly in YS and FR (P < .05). Feelings of vigor increased in YS and tension decreased in FR (P < .05). CONCLUSIONS: YS training tended to decrease blood glucose compared with FR and PP and is equally effective at enhancing body composition, and aerobic fitness in overweight women providing a strong rationale for further research on YS training. PMID- 26901103 TI - The updated Swiss guidelines 2016 for the treatment and follow-up of cutaneous melanoma. AB - Cutaneous melanoma is the most deadly cutaneous neoplasm. In order to guide treatment decisions and follow-up of melanoma patients, guidelines for the management of melanoma in Switzerland were inaugurated in 2001 and revised in 2006 and 2016. Recent data on surgical and medical treatments from randomised trials necessitated modification of the treatment and follow-up recommendations. PMID- 26901104 TI - Response to: a review of the management of 84 cases of nasal polyposis in a Tertiary Otorhinolaryngology Centre: our experience. PMID- 26901107 TI - Correction: Maelstrom promotes hepatocellular carcinoma metastasis by inducing epithelial-mesenchymal transition via Akt/GSK-3beta/snail signaling. PMID- 26901108 TI - Correction: Characterization of the genotype and integration patterns of hepatitis B virus in early- and late-onset hepatocellular carcinoma. PMID- 26901109 TI - What is the clinical relevance of drug-resistant pneumococcus? AB - PURPOSE OF REVIEW: Pneumococcal infections are a major cause of morbidity and mortality worldwide. In recent years, Streptococcus pneumoniae has shown increasing resistance to a several antibiotics, becoming a worldwide problem. The impact of antibiotic resistance of S. pneumoniae on clinical outcomes is still controversial. The principal reason for this controversy is the existence of several factors related to the patients and to the pathogen that may influence how antibiotic resistance patterns affect clinical outcomes. The aim of this review is to discuss current knowledge of the epidemiological data on antibiotic resistance; we also discuss mechanisms and risk factors for antibiotic resistance. RECENT FINDINGS: The phenomenon of serotype replacement after the introduction of conjugate pneumococcal vaccinations and the escalation of antibiotic resistance worldwide remains an important issue in terms of their impact on clinical outcomes in pneumococcal disease. Antimicrobial resistance of pneumococcus leads to changes in the clinical presentation of pneumococcal disease, making it more difficult to diagnose and to treat. Consumption of antibiotics in the community is directly proportional to antimicrobial resistance. Carriage of S. pneumoniae and infection with antibiotic-resistant pneumococcus is associated with prior antibiotic therapy, extremes of age, presence of comorbidities (i.e. COPD), attendance at child day care centers, crowded conditions, intra-familial transmission, and nursing home residence. SUMMARY: Antibiotic-resistant S. pneumoniae is a worldwide problem. The implementation of several strategies including vaccine campaigns, prudent use of current antibiotics, and programs for the surveillance of pneumococcal infections, could limit the increasing resistance of this pathogen to antimicrobials. PMID- 26901106 TI - PI3K/AKT/mTOR-dependent stabilization of oncogenic far-upstream element binding proteins in hepatocellular carcinoma cells. AB - Transcription factors of the far-upstream element-binding protein (FBP) family represent cellular pathway hubs, and their overexpression in liver cancer (hepatocellular carcinoma [HCC]) stimulates tumor cell proliferation and correlates with poor prognosis. Here we determine the mode of oncogenic FBP overexpression in HCC cells. Using perturbation approaches (kinase inhibitors, small interfering RNAs) and a novel system for rapalog-dependent activation of AKT isoforms, we demonstrate that activity of the phosphatidylinositol-4,5 biphosphate 3-kinase/AKT pathway is involved in the enrichment of nuclear FBP1 and FBP2 in liver cancer cells. In human HCC tissues, phospho-AKT significantly correlates with nuclear FBP1/2 accumulation and expression of the proliferation marker KI67. Mechanistic target of rapamycin (mTOR) inhibition or blockade of its downstream effector eukaryotic translation initiation factor 4E activity equally reduced FBP1/2 concentrations. The mTORC1 inhibitor rapamycin diminishes FBP enrichment in liver tumors after hydrodynamic gene delivery of AKT plasmids. In addition, the multikinase inhibitor sorafenib significantly reduces FBP levels in HCC cells and in multidrug resistance 2-deficient mice that develop HCC due to severe inflammation. Both FBP1/2 messenger RNAs are highly stable, with FBP2 being more stable than FBP1. Importantly, inhibition of phosphatidylinositol-4,5 biphosphate 3-kinase/AKT/mTOR signaling significantly diminishes FBP1/2 protein stability in a caspase-3/-7-dependent manner. CONCLUSION: These data provide insight into a transcription-independent mechanism of FBP protein enrichment in liver cancer; further studies will have to show whether this previously unknown interaction between phosphatidylinositol-4,5-biphosphate 3-kinase/AKT/mTOR pathway activity and caspase-mediated FBP stabilization allows the establishment of interventional strategies in FBP-positive HCCs. PMID- 26901111 TI - Implementation of Milestones-Based Assessment for a Safe and Effective Discharge. PMID- 26901110 TI - Organic Nanoflowers from a Wide Variety of Molecules Templated by a Hierarchical Supramolecular Scaffold. AB - Nanoflowers (NFs) are flowered-shaped particles with overall sizes or features in the nanoscale. Beyond their pleasing aesthetics, NFs have found a number of applications ranging from catalysis, to sensing, to drug delivery. Compared to inorganic based NFs, their organic and hybrid counterparts are relatively underdeveloped mostly because of the lack of a reliable and versatile method for their construction. We report here a method for constructing NFs from a wide variety of biologically relevant molecules (guests), ranging from small molecules, like doxorubicin, to biomacromolecules, like various proteins and plasmid DNA. The method relies on the encapsulation of the guests within a hierarchically structured particle made from supramolecular G-quadruplexes. The size and overall flexibility of the guests dictate the broad morphological features of the resulting NFs, specifically, small and rigid guests favor the formation of NFs with spiky petals, while large and/or flexible guests promote NFs with wide petals. The results from experiments using confocal fluorescence microscopy, and scanning electron microscopy provides the basis for the proposed mechanism for the NF formation. PMID- 26901112 TI - Tucked Away: An Infected Thrombus. PMID- 26901114 TI - Impact of orthodontic treatment on self-esteem and quality of life of adult patients requiring oral rehabilitation. AB - OBJECTIVE: To evaluate whether orthodontic treatment in adults requiring oral rehabilitation is effective for increasing patients' self-esteem and quality of life (QoL). MATERIALS AND METHODS: The sample consisted of 102 adult patients (77 women and 25 men) aged between 18 and 66 years (mean, 35.1 years) requiring oral rehabilitation and orthodontic treatment simultaneously. Rosenberg's Self-Esteem (RSE) Scale and a questionnaire about QoL based on the Oral Health Impact Profile (OHIP-14) were used to determine self-esteem and QoL scores retrospectively. Questionnaires were carried out in two stages, T1 (start of treatment) and T2 (6 months after). To compare score changes between T1 and T2, the data obtained from the RSE Scale were evaluated with paired t tests, and data from the quality-of life questionnaire were assessed by applying descriptive statistics. RESULTS: The results showed a statistically significant increase in self-esteem (P < .001) and a great improvement on patients' QoL. CONCLUSIONS: Orthodontic treatment causes a significant increase in self-esteem and QoL, providing psychological benefits for adult patients in need of oral rehabilitation. PMID- 26901113 TI - The Economic Burden Attributable to a Child's Inpatient Admission for Diarrheal Disease in Rwanda. AB - BACKGROUND: Diarrhea is one of the leading causes of childhood morbidity and mortality. Hospitalization for diarrhea can pose a significant burden to health systems and households. The objective of this study was to estimate the economic burden attributable to hospitalization for diarrhea among children less than five years old in Rwanda. These data can be used by decision-makers to assess the impact of interventions that reduce diarrhea morbidity, including rotavirus vaccine introduction. METHODS: This was a prospective costing study where medical records and hospital bills for children admitted with diarrhea at three hospitals were collected to estimate resource use and costs. Hospital length of stay was calculated from medical records. Costs incurred during the hospitalization were abstracted from the hospital bills. Interviews with the child's caregivers provided data to estimate household costs which included transport costs and lost income. The portion of medical costs borne by insurance and household were reported separately. Annual economic burden before and after rotavirus vaccine introduction was estimated by multiplying the reported number of diarrhea hospitalizations in public health centers and district hospitals by the estimated economic burden per hospitalization. All costs are presented in 2014 US$. RESULTS: Costs for 203 children were analyzed. Approximately 93% of the children had health insurance coverage. Average hospital length of stay was 5.3 +/- 3.9 days. Average medical costs for each child for the illness resulting in a hospitalization were $44.22 +/- $23.74 and the total economic burden was $101, of which 65% was borne by the household. For households in the lowest income quintile, the household costs were 110% of their monthly income. The annual economic burden to Rwanda attributable to diarrhea hospitalizations ranged from $1.3 million to $1.7 million before rotavirus vaccine introduction. CONCLUSION: Households often bear the largest share of the economic burden attributable to diarrhea hospitalization and the burden can be substantial, especially for households in the lowest income quintile. PMID- 26901115 TI - Effect of Actin Organization on the Stiffness of Living Breast Cancer Cells Revealed by Peak-Force Modulation Atomic Force Microscopy. AB - We study the correlation between cytoskeleton organization and stiffness of three epithelial breast cancer cells lines with different degrees of malignancy: MCF 10A (healthy), MCF-7 (tumorigenic/noninvasive), and MDA-MB-231 (tumorigenic/invasive). Peak-force modulation atomic force microscopy is used for high-resolution topography and stiffness imaging of actin filaments within living cells. In healthy cells, local stiffness is maximum where filamentous actin is organized as well-aligned stress fibers, resulting in apparent Young's modulus values up to 1 order of magnitude larger than those in regions where these structures are not observed, but these organized actin fibers are barely observed in tumorigenic cells. We further investigate cytoskeleton conformation in the three cell lines by immunofluorescence confocal microscopy. The combination of both techniques determines that actin stress fibers are present at apical regions of healthy cells, while in tumorigenic cells they appear only at basal regions, where they cannot contribute to stiffness as probed by atomic force microscopy. These results substantiate that actin stress fibers provide a dominant contribution to stiffness in healthy cells, while the elasticity of tumorigenic cells appears not predominantly determined by these structures. We also discuss the effects of the high-frequency indentations inherent to peak-force atomic force microscopy for the identification of mechanical cancer biomarkers. Whereas conventional low loading rate indentations (1 Hz) result in slightly differentiated average stiffness for each cell line, in high-frequency measurements (250 Hz) healthy cells are clearly discernible from both tumorigenic cells with an enhanced stiffness ratio; however, the two cancerous cell lines produced indistinguishable results. PMID- 26901116 TI - High-Performance Liquid Chromatographic Resolution of Neutral and Cationic Hetero[6]Helicenes. AB - Cationic hetero[6]helicenes 1+, 2+ and 3+ have been recently disclosed. Herein we report on their enantiomeric separation using high-performance liquid chromatography. Separation of the antipodes can be achieved in preparative scale on neutral adducts with Chiralcel OD-I or Chiralpak ID CSP. Selectivity factors of 1.90, 1.67, and 1.96 were obtained for 1-H, 2-H, and 3-H, respectively. Separation can also be performed on the carbenium ions on regular Chiralpak IA CSP using water-containing eluents, thus allowing for enantiomeric purity determinations in aqueous environments. Resolution of neutral and cationic helicenes is also achieved on more recently developed LARIHC columns. The versatility of the cyclofructan phases allows for baseline separations for both cases and their loading capabilities are demonstrated. Finally, the configurational stability of 1+, 2+, and 3+ was measured. For each replacement of an oxygen atom by an amino group, the racemization barrier increases significantly (DeltaG? = 29.8, 36.3 and >37 kcal mol(-1) for 1+, 2+, and 3+ respectively). PMID- 26901119 TI - Stable electrical performance observed in large-scale monolayer WSe2(1-x)S2x with tunable band gap. AB - Two-dimensional (2D) semiconductor materials have attracted broad interest due to their unique structures and physical properties. The stability of the 2D-material based devices plays a key role in their practical applications. Here, we report the promising stable electrical performance in the large-scale monolayer WSe2(1 x)S2x with a tunable band gap. Photoluminescence (PL) spectroscopy was utilized to verify the tunable band gap in the as-grown monolayer with a tuning capability of 120 meV. Gated field effect transistor (FET) performance confirmed the p-type transport behavior in monolayer WSe2(1-x)S2x with a high on/off ratio (>10(4)). Top-gated FET configuration improves the carrier mobility with two orders larger than that in the back-gated FET device. After exposure to air for three months, the device performance manifested excellent stability with no source-drain current drop observed. P-type WSe2(1-x)S2x with a tunable band gap is the ideal complement to n-type tunable monolayers in the application of pn junction-related flexible nanodevices. PMID- 26901120 TI - Surface Properties of CH3NH3PbI3 for Perovskite Solar Cells. AB - Perovskite solar cells (PSCs) have attracted considerable interest because of their high potential for solar energy conversion. Power conversion efficiencies of the PSCs have rapidly increased from 3.8 to over 20% only in the past few years. PSCs have several similarities to dye-sensitized solar cells in their device compositions; mesoporous TiO2 (mp-TiO2) is sensitized by light-absorbing components and placed into a medium containing hole transporting materials (HTMs). On the other hand, the perovskite materials for the light-harvesting, for example, CH3NH3PbI3 (MAPbI3), have a greater advantage for the photovoltaic applications; extremely long photocarrier diffusion lengths (over 1 MUm) enable carrier transports without singnificant loss. In this respect, the surface states, that can be possible recombination centers, are also of great importance. Availability of solution processes is another important aspect in terms of low cost fabrication of PSCs. Two-step methods, where PbI2 is first introduced from solution onto a mp-TiO2 film and subsequently transformed into the MAPbI3 by the exposition of a solution containing MAI, suggest that use of such a high PbI2 concentration is crucial to obtain higher performance. The experiments also indicate that the PbI2-rich growth condition modifies TiO2/ or HTM/MAPbI3 interfaces in such a way that the photocarrier transport is improved. Thus, the characteristics of surfaces and interfaces play key roles in the high efficiencies of the PSCs. In this Account, we focus on the structural stability and electronic states of the representative (110), (001), (100), and (101) surfaces of tetragonal MAPbI3, which can be regarded as reasonable model HTM/MAPbI3 interfaces, by use of first-principles calculations. By examining various types of PbIx polyhedron terminations, we found that there are two major phases on all of the four surface facets. They can be classified as vacant- and flat-type terminations, and the former is more stable than the latter under thermodynamically equilibrium conditions. More interestingly, both terminations can coexist especially on the more probable (110) and (001) surfaces. Electronic states, that is, projected density of states, of the stable-vacant and PbI2-rich flat terminations on the two surfaces are almost the same as that in bulk MAPbI3. These surfaces can contribute to the long carrier lifetime actually observed for the PSCs because they have no midgap surface states. Furthermore, the shallow surface states on the (110) and (001) flat terminations can be efficient intermediates for hole transport to HTMs. Consequently, the formation of the flat terminations under the PbI2-rich condition will be beneficial for the improvement of PSC performance. PMID- 26901121 TI - Competitive Coadsorption Dynamics of Viruses and Dissolved Organic Matter to Positively Charged Sorbent Surfaces. AB - Adsorption onto solid-water interfaces is a key process governing the fate and transport of waterborne viruses. Although negatively charged viruses are known to extensively adsorb onto positively charged adsorbent surfaces, virus adsorption in such systems in the presence of negatively charged dissolved organic matter (DOM) as coadsorbate remains poorly studied and understood. This work provides a systematic assessment of the adsorption dynamics of negatively charged viruses (i.e., bacteriophages MS2, fr, GA, and Qbeta) and polystyrene nanospheres onto a positively charged model sorbent surface in the presence of varying DOM concentrations. In all systems studied, DOM competitively suppressed the adsorption of the viruses and nanospheres onto the model surface. Electrostatic repulsion of the highly negatively charged MS2, fr, and the nanospheres impaired their adsorption onto DOM adlayers that formed during the coadsorption process. In contrast, the effect of competition on overall adsorption was attenuated for less-negatively charged GA and Qbeta because these viruses also adsorbed onto DOM adlayer surfaces. Competition in MS2-DOM coadsorbate systems were accurately described by a random sequential adsorption model that explicitly accounts for the unfolding of adsorbed DOM. Consistent findings for viruses and nanospheres suggest that the coadsorbate effects described herein generally apply to systems containing negatively charged nanoparticles and DOM. PMID- 26901123 TI - Sigmoid incision rescue nasoseptal flap technique for endoscopic endonasal skull base surgery. AB - Conclusion The sigmoid-incision (S-I) rescue flap technique has the advantage of both reduced-invasiveness and providing a sufficient surgical corridor for endoscopic endonasal skull base surgery (EESBS). Objective Skull base reconstruction with nasoseptal flap (NSF) is critically important in managing post-operative cerebrospinal fluid (CSF) leakage after tumor removal by EESBS. The NSF needs to be elevated before sphenoidotomy and posterior septectomy to preserve the pedicle. However, most extradural surgery without CSF leakage does not require NSF and, therefore, NSF preparation is often futile. As a result, a rescue flap technique to overcome this problem has been developed, whereby a new S-I rescue flap method is used that enables wide exposure of the sphenoidal rostrum and smooth manipulation of surgical instruments to preserve the NSF pedicle. Materials and methods Starting in April 2014, 19 cases underwent EESBS with S-I rescue flap. Results All patients underwent tumor resection under an adequate operative field with smooth manipulation of surgical instruments. Two complications were experienced. One patient had CSF leak after removal of the nasal packing, but the leakage was successfully closed by conventional NSF. Another patient had epistaxis from the septal wall, but this was controlled by electrocautery. PMID- 26901118 TI - Current state in the development of candidate therapeutic HPV vaccines. AB - The identification of human papillomavirus (HPV) as an etiological factor for HPV associated malignancies creates the opportunity to control these cancers through vaccination. Currently, available preventive HPV vaccines have not yet demonstrated strong evidences for therapeutic effects against established HPV infections and lesions. Furthermore, HPV infections remain extremely common. Thus, there is urgent need for therapeutic vaccines to treat existing HPV infections and HPV-associated diseases. Therapeutic vaccines differ from preventive vaccines in that they are aimed at generating cell-mediated immunity rather than neutralizing antibodies. The HPV-encoded early proteins, especially oncoproteins E6 and E7, form ideal targets for therapeutic HPV vaccines since they are consistently expressed in HPV-associated malignancies and precancerous lesions, playing crucial roles in the generation and maintenance of HPV associated disease. Our review will cover various therapeutic vaccines in development for the treatment of HPV-associated lesions and cancers. Furthermore, we review strategies to enhance vaccine efficacy and the latest clinical trials on therapeutic HPV vaccines. PMID- 26901124 TI - Identification of six novel mutations in Iranian patients with maple syrup urine disease and their in silico analysis. AB - Maple syrup urine disease (MSUD) is a rare inborn error of branched-chain amino acid metabolism. The disease prevalence is higher in populations with elevated rate of consanguineous marriages such as Iran. Different types of disease causing mutations have been previously reported in BCKDHA, BCKDHB, DBT and DLD genes known to be responsible for MSUD phenotype. In this study, two sets of multiplex polymorphic STR (Short Tandem Repeat) markers linked to the above genes were used to aid in homozygosity mapping in order to find probable pathogenic change(s) in the studied families. The families who showed homozygote haplotype for the BCKDHA gene were subsequently sequenced. Our findings showed that exons 2, 4 and 6 contain most of the mutations which are novel. The changes include two single nucleotide deletion (i.e. c. 143delT and c.702delT), one gross deletion covering the whole exon four c.(375+1_376-1)_(8849+1_885-1), two splice site changes (c.1167+1G>T, c. 288+1G>A), and one point mutation (c.731G>A). Computational approaches were used to analyze these two novel mutations in terms of their impact on protein structure. Computational structural modeling indicated that these mutations might affect structural stability and multimeric assembly of branched-chain alpha-keto acid dehydrogenase complex (BCKDC). PMID- 26901122 TI - A Novel Synthetic TLR-4 Agonist Adjuvant Increases the Protective Response to a Clinical-Stage West Nile Virus Vaccine Antigen in Multiple Formulations. AB - West Nile virus (WNV) is a mosquito-transmitted member of the Flaviviridae family that has emerged in recent years to become a serious public health threat. Given the sporadic nature of WNV epidemics both temporally and geographically, there is an urgent need for a vaccine that can rapidly provide effective immunity. Protection from WNV infection is correlated with antibodies to the viral envelope (E) protein, which encodes receptor binding and fusion functions. Despite many promising E-protein vaccine candidates, there are currently none licensed for use in humans. This study investigates the ability to improve the immunogenicity and protective capacity of a promising clinical-stage WNV recombinant E-protein vaccine (WN-80E) by combining it with a novel synthetic TLR-4 agonist adjuvant. Using the murine model of WNV disease, we find that inclusion of a TLR-4 agonist in either a stable oil-in-water emulsion (SE) or aluminum hydroxide (Alum) formulation provides both dose and dosage sparing functions, whereby protection can be induced after a single immunization containing only 100 ng of WN-80E. Additionally, we find that inclusion of adjuvant with a single immunization reduced viral titers in sera to levels undetectable by viral plaque assay. The enhanced protection provided by adjuvanted immunization correlated with induction of a Th1 T-cell response and the resultant shaping of the IgG response. These findings suggest that inclusion of a next generation adjuvant may greatly enhance the protective capacity of WNV recombinant subunit vaccines, and establish a baseline for future development. PMID- 26901125 TI - Management of a Wilms' tumor with intracardiac extension using extracorporeal circulation and deep hypothermic circulatory arrest: Case report and review of the literature. AB - Wilms' tumor is a relatively common malignancy among childhood cancers. However, intracardiac extension of the lesion is rare and challenging. In this report, the authors present a successful management of intracardiac extension of Wilms' tumor in a 3-year-old child using cardiopulmonary bypass and deep hypothermic circulatory arrest. The authors also reviewed the published literature on Wilms' tumor with cardiac extension, which were managed by cardiopulmonary bypass and deep hypothermic circulatory arrest to provide an optimum management plan in this challenging condition. PMID- 26901127 TI - The Composite Structure and Two-Peak Emission Behavior of a Ca1.5Ba0.5Si5O3N6:Eu(2+) Phosphor. AB - A Ca1.5Ba0.5Si5O3N6:Eu(2+) phosphor with a monoclinic lattice in the Cm space group exhibiting a composite structure consisting of CaSi2O2N2-like and BaSi6N8O like structures was examined in terms of structure and luminescence. The luminescent properties of the Ca1.5Ba0.5Si5O3N6:Eu(2+) phosphor could be suitable for light-emitting diode applications since it exhibited a promising yellow (or amber) emission peaking at ~ 570-590 nm at excitations of 450-460 nm. The present investigation was focused on verifying the composite structure by employing quantum mechanical calculations such as the Hartree-Fock ab initio calculation and a density functional theory calculation along with precise structural and compositional analyses. The two-peak emission behavior ascribed to the composite structure was also examined in terms of continuous wave and time-resolved photoluminescence. In addition, the energy transfer between two activator sites ascribed to the composite structure was examined in detail. PMID- 26901126 TI - Does the tail wag the dog? How the structure of a glycosylphosphatidylinositol anchor affects prion formation. AB - There is increasing interest in the role of the glycosylphosphatidylinositol (GPI) anchor attached to the cellular prion protein (PrP(C)). Since GPI anchors can alter protein targeting, trafficking and cell signaling, our recent study examined how the structure of the GPI anchor affected prion formation. PrP(C) containing a GPI anchor from which the sialic acid had been removed (desialylated PrP(C)) was not converted to PrP(Sc) in prion-infected neuronal cell lines and in scrapie-infected primary cortical neurons. In uninfected neurons desialylated PrP(C) was associated with greater concentrations of gangliosides and cholesterol than PrP(C). In addition, the targeting of desialylated PrP(C) to lipid rafts showed greater resistance to cholesterol depletion than PrP(C). The presence of desialylated PrP(C) caused the dissociation of cytoplasmic phospholipase A2 (cPLA2) from PrP-containing lipid rafts, reduced the activation of cPLA2 and inhibited PrP(Sc) production. We conclude that the sialic acid moiety of the GPI attached to PrP(C) modifies local membrane microenvironments that are important in PrP-mediated cell signaling and PrP(Sc) formation. PMID- 26901128 TI - Antibody response to respiratory syncytial virus infection in children <18 months old. AB - The development of a safe and effective respiratory syncytial virus (RSV) vaccine might be facilitated by knowledge of the natural immune response to this virus. The aims of this study were to evaluate the neutralizing antibody response of a cohort of healthy children <18 months old to RSV infection. During the RSV season, 89 healthy children <18 months old were enrolled and followed up weekly for 12 weeks. At each visit, a nasopharyngeal swab was obtained for RSV detection by real-time polymerase chain reaction (PCR). During the study period, 2 blood samples were drawn and they were used to determine RSV geometric mean neutralizing antibody titres (GMT) against RSV. A total of 35 (39.3%) children had RSV detected during the study period. Among RSV-positive patients, children >=7 months showed a significantly higher increase in antibody response (p<0.001). A significantly higher number of patients with a >=4 -fold increase in GMT were >=7 months old (p = 0.02) and presented lower respiratory tract infections (LRTIs) during the study period (p = 0.01). Viral shedding was longer among children aged >=7 months (p = 0.06), those with viral load >=10(6) copies/mL (p = 0.03), and those with LRTIs during the study period (p = 0.03), but it was not associated with the immune response (p = 0.41). In conclusion, natural RSV infection seems to evoke a low immune response in younger children. To be effective in this infant population, which is at highest risk of developing severe LRTIs, vaccines must be able to induce in the first months of life a stronger immune response than that produced by the natural infection. PMID- 26901129 TI - Intermuscular Coherence in Normal Adults: Variability and Changes with Age. AB - We investigated beta-band intermuscular coherence (IMC) in 92 healthy adults stratified by decade of age, and analysed variability between and within subjects. In the dominant upper limb, IMC was estimated between extensor digitorum communis and first dorsal interosseous as well as between flexor digitorum superficialis and first dorsal interosseous. In the ipsilateral lower limb, IMC was measured between medial gastrocnemius and extensor digitorum brevis as well as between tibialis anterior and extensor digitorum brevis. Age-related changes in IMC were analysed with age as a continuous variable or binned by decade. Intrasession variance of IMC was examined by dividing sessions into pairs of epochs and comparing coherence estimates between these pairs. Eight volunteers returned for a further session after one year, allowing us to compare intrasession and intersession variance. We found no age-related changes in IMC amplitude across almost six decades of age, allowing us to collate data from all ages into an aggregate normative dataset. Interindividual variability ranged over two orders of magnitude. Intrasession variance was significantly greater than expected from statistical variability alone, and intersession variance was even larger. Potential contributors include fluctuations in task performance, differences in electrode montage and short-term random variation in central coupling. These factors require further exploration and, where possible, minimisation. This study provides evidence that coherence is remarkably robust to senescent changes in the nervous system and provides a large normative dataset for future applications of IMC as a biomarker in disease states. PMID- 26901130 TI - Education and Self-Reported Health: Evidence from 23 Countries on the Role of Years of Schooling, Cognitive Skills and Social Capital. AB - We examine the contribution of human capital to health in 23 countries worldwide using the OECD Survey of Adult Skills, a unique large-scale international assessment of 16-65 year olds that contains information about self-reported health, schooling, cognitive skills and indicators of interpersonal trust, which represents the cognitive dimension of social capital. We identify cross-national differences in education, skill and social capital gradients in self-reported health and explore the interaction between human capital and social capital to examine if and where social capital is a mediator or a moderator of years of schooling and cognitive abilities. We find large education gaps in self-reported health across all countries in our sample and a strong positive relationship between self-reported health and both literacy and trust in the majority of countries. Education and skill gradients in self-reported health appear to be largest in the United States and smallest in Italy, France, Sweden and Finland. On average around 5.5% of both the schooling gap in self-reported health and the literacy gap in self-reported health can be explained by the higher levels of interpersonal trust that better educated/more skilled individuals have, although the mediating role of trust varies considerably across countries. We find no evidence of a moderation effect: the relationships between health and years of schooling and health and cognitive skills are similar among individuals with different levels of trust. PMID- 26901132 TI - Laparoscopic Radiofrequency Ablation for Large Subcapsular Hepatic Hemangiomas: Technical and Clinical Outcomes. AB - OBJECTIVES: The aim of this study was to evaluate the technical and clinical outcomes of using laparoscopic radiofrequency (RF) ablation for treating large subcapsular hepatic hemangiomas. METHODS: We retrospectively reviewed our sequential experience of treating 124 large subcapsular hepatic hemangiomas in 121 patients with laparoscopic RF ablation. RESULTS: The mean diameter of the 124 hemangiomas was 9.1 +/- 3.2 cm (5.0-16.0 cm). RF ablation was performed successfully in all patients. There were 55 complications related to the ablation in 26 patients, including 5 of 69 (7.3%) patients with hemangioma <10 cm and 21 of 52 (40.4%) patients with hemangiomas >=10 cm (P < 0.001). No injuries to abdominal viscera occurred in all the 121 patients. According to the Dindo Clavien classification, all the complications were minor in 26 patients (Grade I). Out of 124 hepatic hemangiomas, 118 (95.2%) were completely ablated, including 70 of 72 (97.2%) lesions < 10 cm and 48 of 52 (92.3%) lesions >= 10 cm (P = 0.236). CONCLUSION: Laparoscopic RF ablation therapy is a safe, feasible and effective procedure for large subcapsular hepatic hemangiomas, even in the hepatic hemangiomas >= 10 cm. Its use avoids thermal injury to the abdominal viscera. PMID- 26901131 TI - Bacillus subtilis extracytoplasmic function (ECF) sigma factors and defense of the cell envelope. AB - Bacillus subtilis provides a model for investigation of the bacterial cell envelope, the first line of defense against environmental threats. Extracytoplasmic function (ECF) sigma factors activate genes that confer resistance to agents that threaten the integrity of the envelope. Although their individual regulons overlap, sigma(W) is most closely associated with membrane active agents, sigma(X) with cationic antimicrobial peptide resistance, and sigma(V) with resistance to lysozyme. Here, I highlight the role of the sigma(M) regulon, which is strongly induced by conditions that impair peptidoglycan synthesis and includes the core pathways of envelope synthesis and cell division, as well as stress-inducible alternative enzymes. Studies of these cell envelope stress responses provide insights into how bacteria acclimate to the presence of antibiotics. PMID- 26901133 TI - Gender Gap in the ERASMUS Mobility Program. AB - Studying abroad has become very popular among students. The ERASMUS mobility program is one of the largest international student exchange programs in the world, which has supported already more than three million participants since 1987. We analyzed the mobility pattern within this program in 2011-12 and found a gender gap across countries and subject areas. Namely, for almost all participating countries, female students are over-represented in the ERASMUS program when compared to the entire population of tertiary students. The same tendency is observed across different subject areas. We also found a gender asymmetry in the geographical distribution of hosting institutions, with a bias of male students in Scandinavian countries. However, a detailed analysis reveals that this latter asymmetry is rather driven by subject and consistent with the distribution of gender ratios among subject areas. PMID- 26901134 TI - Multi Texture Analysis of Colorectal Cancer Continuum Using Multispectral Imagery. AB - PURPOSE: This paper proposes to characterize the continuum of colorectal cancer (CRC) using multiple texture features extracted from multispectral optical microscopy images. Three types of pathological tissues (PT) are considered: benign hyperplasia, intraepithelial neoplasia and carcinoma. MATERIALS AND METHODS: In the proposed approach, the region of interest containing PT is first extracted from multispectral images using active contour segmentation. This region is then encoded using texture features based on the Laplacian-of-Gaussian (LoG) filter, discrete wavelets (DW) and gray level co-occurrence matrices (GLCM). To assess the significance of textural differences between PT types, a statistical analysis based on the Kruskal-Wallis test is performed. The usefulness of texture features is then evaluated quantitatively in terms of their ability to predict PT types using various classifier models. RESULTS: Preliminary results show significant texture differences between PT types, for all texture features (p-value < 0.01). Individually, GLCM texture features outperform LoG and DW features in terms of PT type prediction. However, a higher performance can be achieved by combining all texture features, resulting in a mean classification accuracy of 98.92%, sensitivity of 98.12%, and specificity of 99.67%. CONCLUSIONS: These results demonstrate the efficiency and effectiveness of combining multiple texture features for characterizing the continuum of CRC and discriminating between pathological tissues in multispectral images. PMID- 26901135 TI - A Comprehensive Analysis of the Phylogeny, Genomic Organization and Expression of Immunoglobulin Light Chain Genes in Alligator sinensis, an Endangered Reptile Species. AB - Crocodilians are evolutionarily distinct reptiles that are distantly related to lizards and are thought to be the closest relatives of birds. Compared with birds and mammals, few studies have investigated the Ig light chain of crocodilians. Here, employing an Alligator sinensis genomic bacterial artificial chromosome (BAC) library and available genome data, we characterized the genomic organization of the Alligator sinensis IgL gene loci. The Alligator sinensis has two IgL isotypes, lambda and kappa, the same as Anolis carolinensis. The Iglambda locus contains 6 Clambda genes, each preceded by a Jlambda gene, and 86 potentially functional Vlambda genes upstream of (Jlambda-Clambda)n. The Igkappa locus contains a single Ckappa gene, 6 Jkappas and 62 functional Vkappas. All VL genes are classified into a total of 31 families: 19 Vlambda families and 12 Vkappa families. Based on an analysis of the chromosomal location of the light chain genes among mammals, birds, lizards and frogs, the data further confirm that there are two IgL isotypes in the Alligator sinensis: Iglambda and Igkappa. By analyzing the cloned Iglambda/kappa cDNA, we identified a biased usage pattern of V families in the expressed Vlambda and Vkappa. An analysis of the junctions of the recombined VJ revealed the presence of N and P nucleotides in both expressed lambda and kappa sequences. Phylogenetic analysis of the V genes revealed V families shared by mammals, birds, reptiles and Xenopus, suggesting that these conserved V families are orthologous and have been retained during the evolution of IgL. Our data suggest that the Alligator sinensis IgL gene repertoire is highly diverse and complex and provide insight into immunoglobulin gene evolution in vertebrates. PMID- 26901137 TI - Evaluation of selected endocrine disorders after anticancer treatment of solid tumors in childhood. PMID- 26901136 TI - Identification of Novel Candidate Genes for Early-Onset Colorectal Cancer Susceptibility. AB - Approximately 25-30% of colorectal cancer (CRC) cases are expected to result from a genetic predisposition, but in only 5-10% of these cases highly penetrant germline mutations are found. The remaining CRC heritability is still unexplained, and may be caused by a hitherto-undefined set of rare variants with a moderately penetrant risk. Here we aimed to identify novel risk factors for early-onset CRC using whole-exome sequencing, which was performed on a cohort of CRC individuals (n = 55) with a disease onset before 45 years of age. We searched for genes that were recurrently affected by rare variants (minor allele frequency <= 0.001) with potentially damaging effects and, subsequently, re-sequenced the candidate genes in a replication cohort of 174 early-onset or familial CRC individuals. Two functionally relevant genes with low frequency variants with potentially damaging effects, PTPN12 and LRP6, were found in at least three individuals. The protein tyrosine phosphatase PTP-PEST, encoded by PTPN12, is a regulator of cell motility and LRP6 is a component of the WNT-FZD-LRP5-LRP6 complex that triggers WNT signaling. All variants in LRP6 were identified in individuals with an extremely early-onset of the disease (<=30 years of age), and two of the three variants showed increased WNT signaling activity in vitro. In conclusion, we present PTPN12 and LRP6 as novel candidates contributing to the heterogeneous susceptibility to CRC. PMID- 26901138 TI - Reasons for the discontinuation of therapy of personal insulin pump in children with type 1 diabetes. AB - INTRODUCTION: Pump discontinuation is rare. It is estimated that only about 4% of patients return to multiple daily injections (MDI). OBJECTIVE: To study the factors that influence the decision to stop continuous subcutaneous insulin infusion therapy (CSII). MATERIAL AND METHODS: Analysis of the anonymous questionnaires indicating factors that influenced pump discontinuation and return to the MDI. RESPONDENTS: 30 children (17girls), mean age 14.3yr(+/- 3,57), at the start of CSII 11.06yr(+/- 4.01), at discontinuation of pump therapy 13,23yr(+/ 3,82). RESULTS: The mean duration of pump usage was significantly higher in boys: 3.28yr+/-2.31 vs 1, 27yr+/-1.04(p=0.01); mean HbA1c: boys-8.03%+/-1.03, girls 7.78+/-1.42. The most frequently reported disconnection reasons were: greater sense of disease (93%), difficulties in doing sports (70%), worse well-being during pump therapy (63%), having to attach the pump to the body (60%), embarrassment (56%), adhesions and pain in the place of needle insertion (50%), difficulties in controlling glycemia during physical exercise, fear (43%), high levels of HbA1c (36%), frequent blood glucose monitoring (26%). Problems with technical operation of the pump or frequent episodes of severe hypoglycemia or ketoacidosis were not reported. Among those who indicated difficulty in controlling glycaemia during physical exercise or infection, the average age at the time of quitting the pump was significantly lower than the rest: 12.3+/-3.33 vs. 14.69 +/-2.82 (p=0.04). CONCLUSIONS: The individual psycho-emotional state of the child and appropriate education are important at the start and continuation of CSII. PMID- 26901139 TI - [Overweight, obesity and lipids abnormalities in adolescents with type 1 diabetes]. AB - INTRODUCTION: Overweight children are growing problem as in the pediatric, as well in the diabetic population. The aim of the study was to research the percentage of overweight and obesity in a group of adolescents with type 1 diabetes, and to analyzethe lipid parameters, as well risk factors of these abnormalities. MATERIAL AND METHODS: The study group consist of 60 type 1 diabetic adolescents (including 32 girls, 53.3%), aged above 12 years (mean age for girls 14.6+/-0,3years, boys 15.6+/-0.4 years) with diabetes duration (girls 5.7+-0.6 years, boys 4.4+/-0.8 years). Statistical analysis was performed using Statistica v 9.0 and SPSS v20. RESULTS: The study revealed that boys with type 1 diabetes are significantly higher than healthy population, with weight, waist circumference and BMI comparable to the healthy counterparts. However, diabetic girls are more likely to be overweight and have bigger waist circumference, and higher BMI than the healthy population. Overweight were 12 adolescents (20%) using BMI >=1SD criterion, and 10 (16%) using waist circumference as obesity parameter. Logistic regression revealed that the most important factors for obesity and abdominal obesity are female gender (OR=2.43 and OR=4.56for obesity and abdominal, respectively), diabetes duration above 5 years (respectively OR=1.96 and OR=3.27) and poor metabolic control (respectively OR=1.74 and OR=2.89). CONCLUSIONS: The most important risk factor for obesity in adolescents with type 1 diabetes is female gender. Lipids profile is closely dependent on metabolic control and mass excess. Diabetes duration, metabolic control and lipids profile are significant risk factors for overweight and abdominal obesity. PMID- 26901140 TI - [New onset diabetes after transplantation]. PMID- 26901141 TI - LPL gene mutation as the cause of severe hypertriglyceridemia in the course of ketoacidosis in a patient with newly diagnosed type 1 diabetes mellitus. AB - INTRODUCTION: Severe hypertriglyceridemia is a condition associated with extremely high triglycerides (TG) plasma concentrations exceeding 1000mg/dl. This condition may result in mutations in genes encoding lipoprotein lipase (LPL), apolipoprotein C2 (APOC2) and apolipoprotein A5 (APOA5) characterized by an autosomal recessive inheritance pattern. AIM: A case report of a patient in which clinical picture of type 1 diabetes mellitus (T1DM) was accompanied by diabetic ketoacidosis (DKA) and severe hypertriglyceridemia. CASE REPORT: A 2.5-year-old boy was admitted to the hospital with ketoacidosis (pH - 7.0, BE - 20mmol/l, HCO3 10mmol/l), glucose level of 850mg%, hyponatremia (Na 100mmol/l) and hyperlipidemia (TG 13493 mg/dl, TC 734 mg/dl). The administered treatment resulted in nearly normal glycemic values and lipid disturbances normalization. This child was diagnosed with a heterozygous mutation of the LPL gene. Currently with an intensive insulin therapy and correct metabolic control of type 1 diabetes mellitus (T1DM), this patient maintains a normal lipid profile. CONCLUSION: In patient with T1DM the diagnosis of severe hypertriglyceridemia in the course of ketoacidosis should be based on careful interpretation of laboratory tests results. Moreover genetic tests of the patient and his/her immediate relatives blood samples should be performed. PMID- 26901142 TI - Down syndrome and hyperthyroidism - two case reports. PMID- 26901144 TI - Letter: Evaluating Risks and Benefit of Deep Brain Stimulation for Treatment Refractory Tourette Syndrome. PMID- 26901143 TI - 4E-BP1, a multifactor regulated multifunctional protein. AB - Eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1) is a member of a family of translation repressor proteins, and a well-known substrate of mechanistic target of rapamycin (mTOR) signaling pathway. Phosphorylation of 4E-BP1 causes its release from eIF4E to allow cap-dependent translation to proceed. Recently, 4E-BP1 was shown to be phosphorylated by other kinases besides mTOR, and overexpression of 4E-BP1 was found in different human carcinomas. In this review, we summarize the novel findings on mTOR independent 4E-BP1 phosphorylation in carcinomas. The implications of overexpression and possible multi-function of 4E-BP1 are also discussed. PMID- 26901145 TI - Commentary: Rates and Predictors of Seizure Freedom With Vagus Nerve Stimulation for Intractable Epilepsy. PMID- 26901146 TI - In Reply: Glioblastoma Resection Guided by Flow Cytometry. PMID- 26901147 TI - Model predictive control of two-step nitrification and its validation via short cut nitrification tests. AB - Short-cut nitrification (SCN) is shown to be an attractive technology due to its savings in aeration and external carbon source addition cost. However, the shortage of excluding nitrite nitrogen as a model state in an Activated Sludge Model limits the model predictive control of biological nitrogen removal via SCN. In this paper, a two-step kinetic model was developed based on the introduction of pH and temperature as process controller, and it was implemented in an SBR reactor. The simulation results for optimizing operating conditions showed that with increasing of dissolved oxygen (DO) the rate of ammonia oxidation and nitrite accumulation firstly increased in order to achieve a SCN process. By further increasing DO, the SCN process can be transformed into a complete nitrification process. In addition, within a certain range, increasing sludge retention time and aeration time are beneficial to the accumulation of nitrite. The implementation results in the SBR reactor showed that the data predicted by the kinetic model are in agreement with the data obtained, which indicate that the two-step kinetic model is appropriate to simulate the ammonia removal and nitrite production kinetics. PMID- 26901148 TI - Colonic leishmaniasis in a patient with HIV: a case report. AB - BACKGROUND: To describe an unusual clinical presentation of visceral leishmaniasis affecting the colon. CASE REPORT: We report the case of an HIV positive patient with visceral leishmaniasis. We describe the clinical case, the procedures performed, the treatment provided and the patient's evolution. A comparative table of previously reported similar cases is shown. DISCUSSION: Visceral leishmaniasis with intestinal involvement is an uncommon process. Nevertheless, this possibility should be taken into consideration in the differential diagnosis of immunosuppressed patients with symptoms of diarrhea, as a favorable prognosis depends on early diagnosis and appropriate treatment. PMID- 26901149 TI - Modulatory Effects of Attention on Lateral Inhibition in the Human Auditory Cortex. AB - Reduced neural processing of a tone is observed when it is presented after a sound whose spectral range closely frames the frequency of the tone. This observation might be explained by the mechanism of lateral inhibition (LI) due to inhibitory interneurons in the auditory system. So far, several characteristics of bottom up influences on LI have been identified, while the influence of top down processes such as directed attention on LI has not been investigated. Hence, the study at hand aims at investigating the modulatory effects of focused attention on LI in the human auditory cortex. In the magnetoencephalograph, we present two types of masking sounds (white noise vs. withe noise passing through a notch filter centered at a specific frequency), followed by a test tone with a frequency corresponding to the center-frequency of the notch filter. Simultaneously, subjects were presented with visual input on a screen. To modulate the focus of attention, subjects were instructed to concentrate either on the auditory input or the visual stimuli. More specific, on one half of the trials, subjects were instructed to detect small deviations in loudness in the masking sounds while on the other half of the trials subjects were asked to detect target stimuli on the screen. The results revealed a reduction in neural activation due to LI, which was larger during auditory compared to visual focused attention. Attentional modulations of LI were observed in two post-N1m time intervals. These findings underline the robustness of reduced neural activation due to LI in the auditory cortex and point towards the important role of attention on the modulation of this mechanism in more evaluative processing stages. PMID- 26901151 TI - Control of T cell antigen reactivity via programmed TCR downregulation. AB - The T cell antigen receptor (TCR) is unique in that its affinity for ligand is unknown before encounter and can vary by orders of magnitude. How the immune system regulates individual T cells that display very different reactivity to antigen remains unclear. Here we found that activated CD4(+) T cells, at the peak of clonal expansion, persistently downregulated their TCR expression in proportion to the strength of the initial antigen recognition. This programmed response increased the threshold for cytokine production and recall proliferation in a clone-specific manner and ultimately excluded clones with the highest antigen reactivity. Thus, programmed downregulation of TCR expression represents a negative feedback mechanism for constraining T cell effector function with a suitable time delay to thereby allow pathogen control while avoiding excess inflammatory damage. PMID- 26901150 TI - The microRNA miR-148a functions as a critical regulator of B cell tolerance and autoimmunity. AB - Autoreactive B cells have critical roles in a large diversity of autoimmune diseases, but the molecular pathways that control these cells remain poorly understood. We performed an in vivo functional screen of a lymphocyte-expressed microRNA library and identified miR-148a as a potent regulator of B cell tolerance. Elevated miR-148a expression impaired B cell tolerance by promoting the survival of immature B cells after engagement of the B cell antigen receptor by suppressing the expression of the autoimmune suppressor Gadd45alpha, the tumor suppressor PTEN and the pro-apoptotic protein Bim. Furthermore, increased expression of miR-148a, which occurs frequently in patients with lupus and lupus prone mice, facilitated the development of lethal autoimmune disease in a mouse model of lupus. Our studies demonstrate a function for miR-148a as a regulator of B cell tolerance and autoimmunity. PMID- 26901153 TI - New Introductions, Spread of Existing Matrilines, and High Rates of Pyrethroid Resistance Result in Chronic Infestations of Bed Bugs (Cimex lectularius L.) in Lower-Income Housing. AB - Infestations of the common bed bug (Cimex lectularius L.) have increased substantially in the United States in the past 10-15 years. The housing authority in Harrisonburg, Virginia, conducts heat-treatments after bed bugs are detected in a lower-income housing complex, by treating each infested unit at 60 degrees C for 4-6 hours. However, a high frequency of recurrent infestations called into question the efficacy of this strategy. Genetic analysis using Bayesian clustering of polymorphic microsatellite loci from 123 bed bugs collected from 23 units from May 2012 to April 2013 in one building indicated that (a) 16/21 (73%) infestations were genetically similar, suggesting ineffective heat-treatments or reintroductions from within the building or from a common external source, followed by local spread of existing populations; and (b) up to 5 of the infestations represented new genotypes, indicating that 5 new populations were introduced into this building in one year, assuming they were not missed in earlier screens. There was little to no gene flow among the 8 genetic clusters identified in the building. Bed bugs in the U.S. often possess one or both point mutations in the voltage-gated sodium channel, termed knockdown resistance (kdr), from valine to leucine (V419L) and leucine to isoleucine (L925I) that confer target-site resistance against pyrethroid insecticides. We found that 48/121 (40%) bed bugs were homozygous for both kdr mutations (L419/I925), and a further 59% possessed at least one of the kdr mutations. We conclude that ineffective heat treatments, new introductions, reintroductions and local spread, and an exceptionally high frequency of pyrethroid resistance are responsible for chronic infestations in lower-income housing. Because heat treatments fail to protect from reintroductions, and pesticide use has not decreased the frequency of infestations, preventing new introductions and early detection are the most effective strategies to avoid bed bug infestations in multistory apartment buildings. PMID- 26901154 TI - Multimodal EEG Recordings, Psychometrics and Behavioural Analysis. AB - High spatial and temporal resolution measurements of neuronal activity are preferably combined. In an overview on how this approach can take shape, multimodal electroencephalography (EEG) is treated in 2 main parts: by experiments without a task and in the experimentally cued working brain. It concentrates first on the alpha rhythm properties and next on data-driven search for patterns such as the default mode network. The high-resolution volumic distributions of neuronal metabolic indices result in distributed cortical regions and possibly relate to numerous nuclei, observable in a non-invasive manner in the central nervous system of humans. The second part deals with paradigms in which nowadays assessment of target-related networks can align level dependent blood oxygenation, electrical responses and behaviour, taking the temporal resolution advantages of event-related potentials. Evidence-based electrical propagation in serial tasks during performance is now to a large extent attributed to interconnected pathways, particularly chronometry-dependent ones, throughout a chain including a dorsal stream, next ventral cortical areas taking the flow of information towards inferior temporal domains. The influence of aging is documented, and results of the first multimodal studies in neuropharmacology are consistent. Finally a scope on implementation of advanced clinical applications and personalized marker strategies in neuropsychiatry is indicated. PMID- 26901152 TI - Stromal cells control the epithelial residence of DCs and memory T cells by regulated activation of TGF-beta. AB - Cells of the immune system that reside in barrier epithelia provide a first line of defense against pathogens. Langerhans cells (LCs) and CD8(+) tissue-resident memory T cells (TRM cells) require active transforming growth factor-beta1 (TGF beta) for epidermal residence. Here we found that integrins alphavbeta6 and alphavbeta8 were expressed in non-overlapping patterns by keratinocytes (KCs) and maintained the epidermal residence of LCs and TRM cells by activating latent TGF beta. Similarly, the residence of dendritic cells and TRM cells in the small intestine epithelium also required alphavbeta6. Treatment of the skin with ultraviolet irradiation decreased integrin expression on KCs and reduced the availability of active TGF-beta, which resulted in LC migration. Our data demonstrated that regulated activation of TGF-beta by stromal cells was able to directly control epithelial residence of cells of the immune system through a novel mechanism of intercellular communication. PMID- 26901156 TI - Fetoscopic versus Open Repair for Spina Bifida Aperta: A Systematic Review of Outcomes. AB - OBJECTIVE: To compare outcomes of fetoscopic spina bifida aperta repair (FSBAR) with the results of the open approach (OSBAR) as in the Management Of Myelomeningocele Study (MOMS). METHODS: This was a systematic comparison of reports on FSBAR with data from the MOMS (n = 78). Inclusion criteria were studies of spina bifida aperta patients who underwent FSBAR and were followed for >=12 months. Primary outcome was perinatal mortality. Secondary outcomes included operative, maternal, fetal, neonatal and infant outcomes. RESULTS: Out of 16 reports, we included 5 from 2 centers. Due to bias and heterogeneity, analysis was restricted to two overlapping case series (n = 51 and 71). In those, FSBAR was technically different from OSBAR, had comparable perinatal mortality (7.8 vs. 2.6%, p = 0.212) and shunt rate at 12 months (45 vs. 40%, p = 0.619), longer operation time (223 vs. 105 min, p < 0.001), higher preterm prelabor membrane rupture rate (84 vs. 46%, p < 0.001), earlier gestational age at birth (32.9 vs. 34.1 weeks, p = 0.03), higher postnatal reoperation rate (28 vs. 2.56%, p < 0.001) and absence of uterine thinning or dehiscence (0 vs. 36%, p < 0.001). Functional outcomes were not available. CONCLUSION: FSBAR utilizes a different neurosurgical technique, takes longer to complete, induces more prematurity, requires additional postnatal procedures, yet has a comparable shunt rate and is not associated with uterine thinning or dehiscence. Long-term functional data are awaited. PMID- 26901155 TI - Chronic Administration of Benzo(a)pyrene Induces Memory Impairment and Anxiety Like Behavior and Increases of NR2B DNA Methylation. AB - BACKGROUND: Recently, an increasing number of human and animal studies have reported that exposure to benzo(a)pyrene (BaP) induces neurological abnormalities and is also associated with adverse effects, such as tumor formation, immunosuppression, teratogenicity, and hormonal disorders. However, the exact mechanisms underlying BaP-induced impairment of neurological function remain unclear. The aim of this study was to examine the regulating mechanisms underlying the impact of chronic BaP exposure on neurobehavioral performance. METHODS: C57BL mice received either BaP in different doses (1.0, 2.5, 6.25 mg/kg) or olive oil twice a week for 90 days. Memory and emotional behaviors were evaluated using Y-maze and open-field tests, respectively. Furthermore, levels of mRNA expression were measured by using qPCR, and DNA methylation of NMDA receptor 2B subunit (NR2B) was examined using bisulfate pyrosequencing in the prefrontal cortex and hippocampus. RESULTS: Compared to controls, mice that received BaP (2.5, 6.25 mg/kg) showed deficits in short-term memory and an anxiety-like behavior. These behavioral alterations were associated with a down-regulation of the NR2B gene and a concomitant increase in the level of DNA methylation in the NR2B promoter in the two brain regions. CONCLUSIONS: Chronic BaP exposure induces an increase in DNA methylation in the NR2B gene promoter and down-regulates NR2B expression, which may contribute to its neurotoxic effects on behavioral performance. The results suggest that NR2B vulnerability represents a target for environmental toxicants in the brain. PMID- 26901157 TI - Long-Term Outcomes of Hepatitis-C-Infected Patients Achieving a Sustained Virological Response and Undergoing Radical Treatment for Hepatocellular Carcinoma. AB - BACKGROUND AND AIMS: A sustained virological response (SVR) decreases the incidence of hepatocellular carcinoma (HCC) in patients with hepatitis C. We investigated the long-term outcomes of patients who developed HCC after achieving SVR with interferon therapy. PATIENTS: Of 75 patients who developed HCC after SVR, 40 patients underwent radical therapies (SVR group). From 436 patients undergoing surgical resection for hepatitis C virus-positive HCC, 80 patients were randomly chosen as a control cohort, after adjusting for age, gender, and extent of hepatic fibrosis (non-SVR group). Patients were observed for a median of 5.08 years. RESULTS: HCC recurrence was found in 16 SVR patients and in 66 non SVR patients. The respective HCC recurrence rates of SVR and non-SVR patients were 23 and 56% at 3 years, 42 and 77% at 5 years, and 53 and 90% at 10 years (p = 0.001). The respective overall survival rates in the SVR and non-SVR groups were 93 and 68% at 5 years, 88 and 34% at 10 years, and 53 and 21% at 15 years (p = 0.001). CONCLUSION: Although SVR patients had a significantly lower HCC recurrence rate than the non-SVR patients, the cumulative recurrence rate of SVR patients increased to 86% at 15 years. PMID- 26901158 TI - The Quantity and Quality of Illegally Imported Products of Animal Origin in Personal Consignments into the European Union Seized at Two German Airports between 2010 And 2014. AB - The import of products of animal origin (POAO) in travellers' personal consignments presents a considerable risk of introducing animal diseases and emerging zoonoses into the European Union. The current regulation (EU) 206/2009 implements strict measures for illegally imported POAO, whereupon non-complying products have to be seized and destroyed regardless. Especially airports serve as global bottlenecks for illegally imported POAO where passenger controls of non European flights are performed by customs and veterinary services in collaboration. Results of these control measures have to be submitted in the form of annual reports to the European Commission. However, few data on qualities and quantities of seizures have been published so far. In this study, POAO seized at two German airports between 2010 and 2014 were analysed in terms of quantities, qualitative categories and region of origin. In most years considered, more than 20 tonnes POAO were seized at each airport. However, reported amounts of seizures seem to be only the tip of the iceberg as an all-passenger control is not feasible and therefore travellers are only spot-checked. The analysis suggests that the organisational structures of both customs and official veterinary services and their different risk perceptions interfere in completing an effective ban on the illegal import of POAO. PMID- 26901160 TI - Intrinsic Disorder to Order Transitions in the Scaffold Phosphoprotein P from the Respiratory Syncytial Virus RNA Polymerase Complex. AB - Intrinsic disorder is at the center of biochemical regulation and is particularly overrepresented among the often multifunctional viral proteins. Replication and transcription of the respiratory syncytial virus (RSV) relies on a RNA polymerase complex with a phosphoprotein cofactor P as the structural scaffold, which consists of a four-helix bundle tetramerization domain flanked by two domains predicted to be intrinsically disordered. Because intrinsic disorder cannot be reduced to a defined atomic structure, we tackled the experimental dissection of the disorder-order transitions of P by a domain fragmentation approach. P remains as a tetramer above 70 degrees C but shows a pronounced reversible secondary structure transition between 10 and 60 degrees C. While the N-terminal module behaves as a random coil-like IDP in a manner independent of tetramerization, the isolated C-terminal module displays a cooperative and reversible metastable transition. When linked to the tetramerization domain, the C-terminal module becomes markedly more structured and stable, with strong ANS binding. Therefore, the tertiary structure in the C-terminal module is not compact, conferring "late" molten globule-like IDP properties, stabilized by interactions favored by tetramerization. The presence of a folded structure highly sensitive to temperature, reversibly and almost instantly formed and broken, suggests a temperature sensing activity. The marginal stability allows for exposure of protein binding sites, offering a thermodynamic and kinetic fine-tuning in order disorder transitions, essential for the assembly and function of the RSV RNA polymerase complex. PMID- 26901159 TI - The Glycoproteins of All Filovirus Species Use the Same Host Factors for Entry into Bat and Human Cells but Entry Efficiency Is Species Dependent. AB - Ebola and marburgviruses, members of the family Filoviridae, can cause severe hemorrhagic fever in humans. The ongoing Ebola virus (EBOV) disease epidemic in Western Africa claimed more than 11,300 lives and was associated with secondary cases outside Africa, demonstrating that filoviruses pose a global health threat. Bats constitute an important natural reservoir of filoviruses, including viruses of the recently identified Cuevavirus genus within the Filoviridae family. However, the interactions of filoviruses with bat cells are incompletely understood. Here, we investigated whether filoviruses employ different strategies to enter human and bat cells. For this, we examined host cell entry driven by glycoproteins (GP) from all filovirus species into cell lines of human and fruit bat origin. We show that all GPs were able to mediate entry into human and most fruit bat cell lines with roughly comparable efficiency. In contrast, the efficiency of entry into the cell line EidNi/41 derived from a straw-colored fruit bat varied markedly between the GPs of different filovirus species. Furthermore, inhibition studies demonstrated that filoviruses employ the same host cell factors for entry into human, non-human primate and fruit bat cell lines, including cysteine proteases, two pore channels and NPC1 (Niemann-Pick C1 molecule). Finally, processing of GP by furin and the presence of the mucin-like domain in GP were dispensable for entry into both human and bat cell lines. Collectively, these results show that filoviruses rely on the same host cell factors for entry into human and fruit bat cells, although the efficiency of the usage of these factors might differ between filovirus species. PMID- 26901161 TI - Vital Sign Prediction of Adverse Maternal Outcomes in Women with Hypovolemic Shock: The Role of Shock Index. AB - OBJECTIVE: To determine the optimal vital sign predictor of adverse maternal outcomes in women with hypovolemic shock secondary to obstetric hemorrhage and to develop thresholds for referral/intensive monitoring and need for urgent intervention to inform a vital sign alert device for low-resource settings. STUDY DESIGN: We conducted secondary analyses of a dataset of pregnant/postpartum women with hypovolemic shock in low-resource settings (n = 958). Using receiver operating curve analysis, we evaluated the predictive ability of pulse, systolic blood pressure, diastolic blood pressure, shock index, mean arterial pressure, and pulse pressure for three adverse maternal outcomes: (1) death, (2) severe maternal outcome (death or severe end organ dysfunction morbidity); and (3) a combined severe maternal and critical interventions outcome comprising death, severe end organ dysfunction morbidity, intensive care admission, blood transfusion >= 5 units, or emergency hysterectomy. Two threshold parameters with optimal rule-in and rule-out characteristics were selected based on sensitivities, specificities, and positive and negative predictive values. RESULTS: Shock index was consistently among the top two predictors across adverse maternal outcomes. Its discriminatory ability was significantly better than pulse and pulse pressure for maternal death (p<0.05 and p<0.01, respectively), diastolic blood pressure and pulse pressure for severe maternal outcome (p<0.01), and systolic and diastolic blood pressure, mean arterial pressure and pulse pressure for severe maternal outcome and critical interventions (p<0.01). A shock index threshold of >= 0.9 maintained high sensitivity (100.0) with clinical practicality, >= 1.4 balanced specificity (range 70.0-74.8) with negative predictive value (range 93.2-99.2), and >= 1.7 further improved specificity (range 80.7-90.8) without compromising negative predictive value (range 88.8 98.5). CONCLUSIONS: For women with hypovolemic shock from obstetric hemorrhage, shock index was consistently a strong predictor of all adverse outcomes. In lower level facilities in low resource settings, we recommend a shock index threshold of >= 0.9 indicating need for referral, >= 1.4 indicating urgent need for intervention in tertiary facilities and >= 1.7 indicating high chance of adverse outcome. The vital sign alert device incorporated values 0.9 and 1.7; however, all thresholds will be prospectively validated and clinical pathways for action appropriate to setting established prior to clinical implementation. PMID- 26901162 TI - A neurotensin analog blocks cocaine-conditioned place preference and reinstatement. AB - Neurotensin (NT) is a neuropeptide that acts as a neurotransmitter and neuromodulator in the central nervous system. Several studies suggest a therapeutic role for NT analogs in nicotine and other psychostimulant addictions. We studied the effects of the nonselective NT receptor agonist NT69L, which has equal affinity for the two major NT receptors, NTS1 and NTS2, on the expression of cocaine-conditioned place preference (cocaine-CPP) and reinstatement after extinction. Robust cocaine-CPP was obtained after 5 days of conditioning. Extinction was induced using eight repeated daily injections of saline. Reinstatement was prompted by priming with one injection of cocaine (12 mg/kg intraperitoneally). On the test day, NT69L (1 mg/kg intraperitoneally) was administered 30 min before assessing cocaine-CPP. Extinction led to the loss of cocaine-CPP. One injection of cocaine (12 mg/kg intraperitoneally) for cocaine priming reinstated cocaine-CPP. NT69L blocked cocaine-CPP reinstatement in cocaine-primed animals. In addition, NT69L blocked cocaine-CPP reinstatement when administered before priming with cocaine. Thus, the NT agonist NT69L blocked both cocaine-CPP and reinstatement to cocaine preference. NT69L may exert this action by modulating the mesocorticolimbic dopamine and glutamatergic pathways involved in addiction and relapse processes. Therefore, NT agonists may represent a novel therapy for the treatment of addiction to cocaine and possibly to other psychostimulants. PMID- 26901163 TI - Regional differences in sorafenib-treated patients with hepatocellular carcinoma: GIDEON observational study. AB - BACKGROUND & AIMS: Treatment approaches for hepatocellular carcinoma (HCC) vary across countries, but these differences and their potential impact on outcomes have not been comprehensively assessed. Data from the multinational GIDEON (Global Investigation of therapeutic DEcisions in HCC and Of its treatment with sorafeNib) registry evaluated differences in patient characteristics, practice patterns and outcomes in HCC across geographical regions in patients who received sorafenib. METHODS: GIDEON is a non-randomised, observational registry study conducted in 39 countries across five global regions. HCC patients in whom a decision to treat with sorafenib was made in clinical practice and according to local practices were included. RESULTS: 3202 patients were evaluable for safety analysis: Asia-Pacific (n = 928), Japan (n = 508), Europe (n = 1113), USA (n = 563) and Latin America (n = 90). Patients in Japan had earlier-stage disease at initial diagnosis compared with patients in other regions (Barcelona Clinic Liver Cancer stage A; 43.7% vs 9.1-24.3%). Use of locoregional therapies before sorafenib, including transarterial chemoembolisation, was more common in Japan (84.4%) and Asia-Pacific (67.2%) compared with the USA (49.4%) and Europe (43.5%). Treatment patterns with respect to sorafenib also differed, with a shorter duration of treatment reported in the USA and Asia-Pacific. Time from initial diagnosis to death was longer in Japan compared with other regions (median, 79.6 months vs 14.8-25.0 months). CONCLUSIONS: Data from GIDEON highlight regional variations in the management of HCC and patient outcomes. Greater standardisation of management may help optimise outcomes for HCC patients. PMID- 26901164 TI - Assessment of Vascularity in Hepatic Alveolar Echinococcosis: Comparison of Quantified Dual-Energy CT with Histopathologic Parameters. AB - PURPOSE: To investigate whether dual-energy computer tomography(DECT) could determine the angiographic vascularity of alveolar echinococcosis lesions by comparing the quantitative iodine concentration (IC) with the microvascular density (MVD). MATERIAL AND METHODS: Twenty-five patients (16 men, 9 women; mean age, 40.9 +/- 13.8 years) with confirmed hepatic alveolar echinococcosis (HAE) underwent DECT of the abdomen, consisting of arterial phase (AP), portal venous phase (PVP), and delayed phase (DP) scanning, in dual-source mode (100 kV/140 kV). Image data were processed with a DECT software algorithm that was designed for the evaluation of iodine distribution in the different layers (marginal zone, solid and cystic) of the lesions. The CT patterns of HAE lesions were classified into three types: solid type, pseudocystic type and 'geographic map' (mixed) type. The IC measurements in different layers and different types of lesions were statistically compared. MVD was examined using CD34 immunohistochemical staining of the resected HAE tissue and scored based on the percentage of positively stained cells and their intensity. Pearson's correlation analysis was used to evaluate the potential correlation between DECT parameters and MVD. RESULTS: A total of 27 HAE lesions were evaluated, of which 9 were solid type, 3 were pseudocystic type and 15 were mixed type. The mean lesion size was 100.7 +/- 47.3 mm. There was a significant difference in the IC measurements between different layers of HAE lesions during each scan phase (p < 0.001). The IC in the marginal zone was significantly higher than in the solid and cystic components in AP (2.15 mg/mL vs. 0.17 or 0.01 mg/mL), PVP (3.08 mg/mL vs. 0.1 or 0.02 mg/mL), and DP (2.93 mg/mL vs. 0.04 or 0.02 mg/mL). No significant difference was found among the different CT patterns of HAE lesions. Positive expression of CD34 in the marginal zones surrounding HAE lesions was found in 92.5% (25/27) of lesions, of which 18.5% (5/27) were strongly positive, 62.7% (17/27) were moderately positive, and 11.1% (3/27) were weakly positive. In contrast, 7.4% (2/27) of the lesions were negative for CD34. There was a positive correlation between IC measurements and MVD in the marginal zone of HAE lesions (r = 0.73, p < 0.05). CONCLUSIONS: The DECT quantitative iodine concentration was significantly correlated with MVD in the marginal zones surrounding HAE lesions. Dual-energy CT using a quantitative analytic methodology can be used to evaluate the vascularity of AE. PMID- 26901166 TI - How Reliable Are Current Data for Assessing the Actual Prevalence of Chronic Obstructive Pulmonary Disease? AB - BACKGROUND: Estimating COPD occurrence is perceived by the scientific community as a matter of increasing interest because of the worldwide diffusion of the disease. We aimed to estimate COPD prevalence by using administrative databases from a city in central Italy for 2002-2006, improving both the sensitivity and the reliability of the estimate. METHODS: Multiple sources were used, integrating the hospital discharge register (HDR), clinical charts, spirometry and the cause specific mortality register (CMR) in a longitudinal algorithm, to reduce underestimation of COPD prevalence. Prevalence was also estimated on the basis of COPD cases confirmed through spirometry, to correct misclassification. Estimating such prevalence relied on using coefficients of validation, derived as the positive predictive value (PPV) for being an actual COPD case from clinical and spirometric data at the Institute of Clinical Physiology of the National Research Council. RESULTS: We found that sensitivity of COPD prevalence increased by 37%. The highest estimate (4.43 per 100 residents) was observed in the 5-year period, using a 3-year longitudinal approach and combined data from three sources. We found that 17% of COPD cases were misclassified. The above estimate of COPD prevalence decreased (3.66 per 100 residents) when coefficients of validation were applied. The PPV was 80% for the HDR, 82% for clinical diagnoses and 91% for the CMR. CONCLUSIONS: Adjusting the COPD prevalence for both underestimation and misclassification of the cases makes administrative data more reliable for epidemiological purposes. PMID- 26901165 TI - How Do Urban Indian Private Practitioners Diagnose and Treat Tuberculosis? A Cross-Sectional Study in Chennai. AB - SETTING: Private practitioners are frequently the first point of healthcare contact for patients with tuberculosis (TB) in India. Inappropriate TB management practices among private practitioners may contribute to delayed TB diagnosis and generate drug resistance. However, these practices are not well understood. We evaluated diagnostic and treatment practices for active TB and benchmarked practices against International Standards for TB Care (ISTC) among private medical practitioners in Chennai. DESIGN: A cross-sectional survey of 228 practitioners practicing in the private sector from January 2014 to February 2015 in Chennai city who saw at least one TB patient in the previous year. Practitioners were randomly selected from both the general community and a list of practitioners who referred patients to a public-private mix program for TB treatment in Chennai. Practitioners were interviewed using standardized questionnaires. RESULTS: Among 228 private practitioners, a median of 12 (IQR 4 28) patients with TB were seen per year. Of 10 ISTC standards evaluated, the median of standards adhered to was 4.0 (IQR 3.0-6.0). Chest physicians reported greater median ISTC adherence than other MD and MS practitioners (score 7.0 vs. 4.0, P<0.001), or MBBS practitioners (score 7.0 vs. 4.0, P<0.001). Only 52% of all practitioners sent >5% of patients with cough for TB testing, 83% used smear microscopy for diagnosis, 33% monitored treatment response, and 22% notified TB cases to authorities. Of 228 practitioners, 68 reported referring all patients with new pulmonary TB for treatment, while 160 listed 27 different regimens; 78% (125/160) prescribed a regimen classified as consistent with ISTC. Appropriate treatment practices differed significantly between chest physicians and other MD and MS practitioners (54% vs. 87%, P<0.001). CONCLUSION: TB management practices in India's urban private sector are heterogeneous and often suboptimal. Private providers must be better engaged to improve diagnostic capacity and decrease TB transmission in the community. PMID- 26901167 TI - Ion Pairing in Alkali Nitrate Electrolyte Solutions. AB - In this study, we investigate the thermodynamics of alkali nitrate salt solutions, especially the formation of contact ion pairs between alkali cation and nitrate anion. The ion-pairing propensity shows an order of LiNO3 < NaNO3 < KNO3. Such results explain the salt activity coefficients and suggest that the empirical "law of matching water affinity" is followed by these alkali nitrate salt solutions. The spatial patterns of contact ion pairs are different in the three salt solutions studied here: Li(+) forms the contact ion pair with only one oxygen of the nitrate while Na(+) and K(+) can also be shared by two oxygens of the nitrate. In reproducing the salt activity coefficient using Kirkwood-Buff theory, we find that it is essential to include electronic polarization for Li(+) which has a high charge density. The electronic continuum correction for nonpolarizable force field significantly improves the agreement between the calculated activity coefficients and their experimental values. This approach also improves the performance of the force field on salt solubility. From these two aspects, this study suggests that electronic continuum correction can be a promising approach to force-field development for ions with high charge densities. PMID- 26901168 TI - Actinobacteria Isolated from an Underground Lake and Moonmilk Speleothem from the Biggest Conglomeratic Karstic Cave in Siberia as Sources of Novel Biologically Active Compounds. AB - Actinobacteria isolated from unstudied ecosystems are one of the most interesting and promising sources of novel biologically active compounds. Cave ecosystems are unusual and rarely studied. Here, we report the isolation and characterization of ten new actinobacteria strains isolated from an ancient underground lake and moonmilk speleothem from the biggest conglomeratic karstic cave in Siberia with a focus on the biological activity of the obtained strains and the metabolite dereplication of one active strain. Streptomyces genera isolates from moonmilk speleothem demonstrated antibacterial and antifungal activities. Some of the strains were able to inhibit the growth of pathogenic Candida albicans. PMID- 26901169 TI - A critical evaluation of the validity of episodic future thinking: A clinical neuropsychology perspective. AB - OBJECTIVE: Episodic future thinking is defined as the ability to mentally simulate a future event. Although episodic future thinking has been studied extensively in neuroscience, this construct has not been explored in depth from the perspective of clinical neuropsychology. The aim of this critical narrative review is to assess the validity and clinical implications of episodic future thinking. METHOD: A systematic review of episodic future thinking literature was conducted. PubMed and PsycInfo were searched through July 2015 for review and empirical articles with the following search terms: "episodic future thinking," "future mental simulation," "imagining the future," "imagining new experiences," "future mental time travel," "future autobiographical experience," and "prospection." RESULTS: The review discusses evidence that episodic future thinking is important for adaptive functioning, which has implications for neurological populations. To determine the validity of episodic future thinking, the construct is evaluated with respect to related constructs, such as imagination, episodic memory, autobiographical memory, prospective memory, narrative construction, and working memory. Although it has been minimally investigated, there is evidence of convergent and discriminant validity for episodic future thinking. Research has not addressed the incremental validity of episodic future thinking. Practical considerations of episodic future thinking tasks and related constructs in a clinical neuropsychological setting are considered. CONCLUSIONS: The utility of episodic future thinking is currently unknown due to the lack of research investigating the validity of episodic future thinking. Future work is discussed, which could determine whether episodic future thinking is an important missing piece in standard clinical neuropsychological assessment. (PsycINFO Database Record PMID- 26901170 TI - Neural correlates of recognition and naming of musical instruments. AB - OBJECTIVE: Retrieval of lexical (names) and conceptual (semantic) information is frequently impaired in individuals with neurological damage. One category of items that is often affected is musical instruments. However, distinct neuroanatomical correlates underlying lexical and conceptual knowledge for musical instruments have not been identified. METHOD: We used a neuropsychological approach to explore the neural correlates of knowledge retrieval for musical instruments. A large sample of individuals with focal brain damage (N = 298), viewed pictures of 16 musical instruments and were asked to name and identify each instrument. Neuroanatomical data were analyzed with a proportional MAP-3 method to create voxelwise lesion proportion difference maps. RESULTS: Impaired naming (lexical retrieval) of musical instruments was associated with damage to the left temporal pole and inferior pre- and postcentral gyri. Impaired recognition (conceptual knowledge retrieval) of musical instruments was associated with a more broadly and bilaterally distributed network of regions, including ventromedial prefrontal cortices, occipital cortices, and superior temporal gyrus. CONCLUSIONS: The findings extend our understanding of how musical instruments are processed at neural system level, and elucidate factors that may explain why brain damage may or may not produce anomia or agnosia for musical instruments. Our findings also help inform broader understanding of category-related knowledge mapping in the brain, as musical instruments possess several characteristics that are similar to various other categories of items: They are inanimate and highly manipulable (similar to tools), produce characteristic sounds (similar to animals), and require fine grained visual differentiation between each other (similar to people). (PsycINFO Database Record PMID- 26901171 TI - Differences in visual naming performance between patients with temporal lobe epilepsy associated with temporopolar lesions versus hippocampal sclerosis. AB - OBJECTIVE: Naming difficulties are frequently observed in patients with temporal lobe epilepsy (TLE). Although damage/removal of regions of the anterior temporal neocortex including the temporal pole is considered critical for those difficulties, 1 relevant hypothesis proposes that hippocampal damage also has a role. Our aim was to better understand the specific involvement of temporal pole and hippocampus in visual object naming. METHOD: We assessed 2 types of patients with TLE on a visual confrontation-naming task: patients with hippocampal sclerosis (HS; n = 16) and patients with a lesion on the tip of the temporal pole that spared the hippocampus entirely (n = 18). A common battery of verbal and nonverbal semantic tasks was administered and used as a semantic memory background. Control group were 20 matched healthy participants. RESULTS: Patients with lesions on their temporal poles differed from patients with HS and control group on naming ability, proportion and rate of error type, and influence of concept familiarity. Of note, naming performance was not affected by hippocampal damage. Using a Bayesian model averaging approach, we found that the number of omission errors distinguished patients with temporal pole damage from patients with HS and controls. This differential pattern occurred despite similar impairment on the semantic memory background in both clinical groups. CONCLUSION: Current findings provide evidence that temporal pole damage produces or contributes to naming impairment in TLE, while also suggesting that the hippocampus is not critical for naming. They also highlight the importance of error-type analysis when evaluating visual naming in TLE. (PsycINFO Database Record PMID- 26901172 TI - Molecular Mechanisms of Inhibition of Streptococcus Species by Phytochemicals. AB - This review paper summarizes the antibacterial effects of phytochemicals of various medicinal plants against pathogenic and cariogenic streptococcal species. The information suggests that these phytochemicals have potential as alternatives to the classical antibiotics currently used for the treatment of streptococcal infections. The phytochemicals demonstrate direct bactericidal or bacteriostatic effects, such as: (i) prevention of bacterial adherence to mucosal surfaces of the pharynx, skin, and teeth surface; (ii) inhibition of glycolytic enzymes and pH drop; (iii) reduction of biofilm and plaque formation; and (iv) cell surface hydrophobicity. Collectively, findings from numerous studies suggest that phytochemicals could be used as drugs for elimination of infections with minimal side effects. PMID- 26901173 TI - Antimicrobial Activity of Some Novel Armed Thiophene Derivatives and Petra/Osiris/Molinspiration (POM) Analyses. AB - Tetrasubstituted 2-acetylthiophene derivative 5 was synthesized and then condensed with various nitrogen nucleophiles such as 5-amino-1,2,4-triazole, 2 aminobenzimidazole, aniline or p-chloroaniline to afford the corresponding iminothiophene derivatives 6-8a,b. Condensation of thiophene 5 with malononitrile as carbon nucleophile afforded compound 9, which underwent nucleophilic addition with DMF-DMA to afford compound 10. The newly synthesized products were characterized by elemental analysis, IR, MS, 1H-(13)C-NMR and CHN analysis and then evaluated for their antimicrobial activity. Results of the in vitro antibacterial activity showed that thiophene derivative 7 was found to be more potent than the standard drug gentamicin against Pseudomonas aeruginosa. Some of these compounds showed potential antimicrobial activities. Molecular docking and Osiris/Molinspiration analyses show the crucial role and impact of substituents on bioactivity and indicate the unfavorable structural parameters in actual drug design: more substitution with electronic donor group doesn't guarantee more effective bioactivity. This study should greatly help in an intelligent and a controlled pharmacomodulation of antibiotics. PMID- 26901174 TI - Novel 2-Phenoxyanilide Congeners Derived from a Hit Structure of the TCAMS: Synthesis and Evaluation of Their in Vitro Activity against Plasmodium falciparum. AB - The Tres Cantos Antimalarial Compound Set (TCAMS) is a publicly available compound library which contains 13533 hit structures with confirmed activity against Plasmodium falciparum, the infective agent responsible for malaria tropica. The TCAMS provides a variety of starting points for the investigation of new antiplasmodial drug leads. One of the promising compounds is TCMDC-137332, which seemed to be a good starting point due to its antiplasmodial potency and its predicted physicochemical properties. Several new analogues based on a 2 phenoxyanilide scaffold were synthesized by standard amide coupling reactions and were fully characterized regarding their identity and purity by spectroscopic and chromatographic methods. Furthermore, the results of the biological evaluation of all congeners against Plasmodium falciparum NF54 strains are presented. The findings of our in vitro screening could not confirm the presumed nanomolar antiplasmodial activity of TCMDC-137332 and its derivatives. PMID- 26901175 TI - Conjugated Oligo-Aromatic Compounds Bearing a 3,4,5-Trimethoxy Moiety: Investigation of Their Antioxidant Activity Correlated with a DFT Study. AB - A series of heterocyclic compounds bearing the well-known free radical scavenging 3,4,5-trimethoxybenzyloxy group, was synthesized. The key compound 4-(3,4,5 trimethoxybenzyl-oxy)benzohydrazide was converted into thiosemicarbazide derivatives, which were subsequently cyclized with NaOH to provide 1,2,4-triazole derivatives. Alternative treatment of the acid hydrazide with carbon disulfide in the presence of KOH led to the corresponding 1,3,4-oxadiazole and various alkylated derivatives. The newly synthesized compounds were purified and the structures of the products were elucidated and confirmed on the basis of their analytical and spectral data. Their antioxidant activities were evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH(*)) and Ferric Reducing Antioxidant Power (FRAP) assays. The thiosemicarbazide derivatives were highly active in both antioxidant assays with the lowest IC50 value for DPPH radical scavenging. Theoretical calculations based on density functional theory (DFT) were performed to understand the relative importance of NH, SH and CH hydrogens on the radical scavenging activities of these compounds. PMID- 26901176 TI - Antimicrobial Activity and Stability of Short and Long Based Arachnid Synthetic Peptides in the Presence of Commercial Antibiotics. AB - Four antimicrobial peptides (AMPs) named Pin2[G], Pin2[14], P18K and FA1 were chemically synthesized and purified. The four peptides were evaluated in the presence of eight commercial antibiotics against four microorganisms of medical importance: Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae. The commercial antibiotics used were amoxicillin, azithromycin, ceftriaxone, gentamicin, levofloxacin, sulfamethoxazole, trimethoprim and vancomycin. The best AMP against P. aeruginosa was the peptide FA1, and the best AMP against S. aureus was Pin2[G]. Both FA1 and Pin2[G] were efficient against E. coli, but they were not effective against K. pneumoniae. As K. pneumoniae was resistant to most of the commercial antibiotics, combinations of the AMPs FA1 and Pin2[G] were prepared with these antibiotics. According to the fractional inhibitory concentration (FIC) index, the best antimicrobial combinations were obtained with concomitant applications of mixtures of FA1 with levofloxacin and sulfamethoxazole. However, combinations of FA1 or Pin2[G] with other antibiotics showed that total inhibitory effect of the combinations were greater than the sum of the individual effects of either the antimicrobial peptide or the antibiotic. We also evaluated the stability of the AMPs. The AMP Pin2[G] manifested the best performance in saline buffer, in supernatants of bacterial growth and in human blood plasma. Nevertheless, all AMPs were cleaved using endoproteolytic enzymes. These data show advantages and disadvantages of AMPs for potential clinical treatments of bacterial infections, using them in conjunction with commercial antibiotics. PMID- 26901177 TI - Screening of Korean Natural Products for Anti-Adipogenesis Properties and Isolation of Kaempferol-3-O-rutinoside as a Potent Anti-Adipogenetic Compound from Solidago virgaurea. AB - In this study, the anti-adipogenetic activity of 300 plant extracts was investigated using an Oil Red O staining assay in a 3T3-L1 cell line. Our results indicate that three plants, including the stem and leaf of Physalis angulata, the whole grass of Solidago virgaurea, and the root of Dioscorea nipponica, produced over 90% inhibition of adipogenesis. Kaempferol-3-O-rutinoside, which demonstrated a 48.2% inhibitory effect on adipogenesis without cytotoxicity, was isolated from the butanol layer of a water extract of S. virgaurea guided by the anti-adipogenesis assay in 3T3-L1. PPAR-gamma and C/EBPalpha expression levels were determined using western blot, and our results indicate that kaempferol-3-O rutinoside has a strong anti-adipogenic effect in 3T3-L1 cells through the suppression of increases in PPAR-gamma and C/EBPalpha expression. PMID- 26901178 TI - Optimization of Ultrasound-Assisted Extraction of Natural Antioxidants from the Osmanthus fragrans Flower. AB - An ultrasound-assisted extraction (UAE) method was developed to extract natural antioxidants from the Osmanthus fragrans flower. The effect of UAE on antioxidant activity of the extract from the Osmanthus fragrans flower was studied using a Trolox equivalent antioxidant capacity (TEAC) assay. Optimization conditions were firstly determined using a single-factor experiment, and response surface methodology was then used to evaluate interaction of several experimental parameters. Analysis of the coefficient of determination showed that second-order polynomial models produced a highly satisfactory fitting of the experimental data with regard to TEAC values (R2 = 0.9829, p < 0.0001). The optimal conditions were 39.1% ethanol, and extraction for 35.2 min at 59.4 degrees C. Under these conditions, the maximum TEAC value was 584.9 +/- 6.0 MUmol Trolox/g DW, which was higher than those obtained by the conventional extracting method (486.4 +/- 12.6 MUmol Trolox/g DW) and the Soxhlet extraction method (339.1 +/- 16.2 MUmol Trolox/g DW). The crude extract obtained could be used either as a food additive or in pharmaceuticals for the prevention and treatment of diseases caused by oxidative stress. PMID- 26901179 TI - Screening and Analysis of the Potential Bioactive Components of Poria cocos (Schw.) Wolf by HPLC and HPLC-MS(n) with the Aid of Chemometrics. AB - The aim of the present study was to establish a new method based on Similarity Analysis (SA), Cluster Analysis (CA) and Principal Component Analysis (PCA) to determine the quality of different samples of Poria cocos (Schw.) Wolf obtained from Yunnan, Hubei, Guizhou, Fujian, Henan, Guangxi, Anhui and Sichuan in China. For this purpose 15 samples from the different habitats were analyzed by HPLC-PAD and HPLC-MS(n). Twenty-three compounds were detected by HPLC-MS(n), of which twenty compounds were tentatively identified by comparing their retention times and mass spectrometry data with that of reference compounds and reviewing the literature. The characteristic fragmentations were summarized. 3-epi Dehydrotumulosic acid (F13), 3-oxo-16alpha,25-dihydroxylanosta-7,9(11),24(31) trien-21-oic acid (F4), 3-oxo-6,16alpha-dihydroxylanosta-7,9(11),24(31)-trien-21 oic acid (F7) and dehydropachymic acid (F15) were deemed to be suitable marker compounds to distinguish between samples of different quality according to CA and PCA. This study provides helpful chemical information for further anti-tumor activity and active mechanism research on P. cocos. The results proved that fingerprint combined with a chemometric approach is a simple, rapid and effective method for the quality discrimination of P. cocos. PMID- 26901180 TI - Synthesis and Structure-Activity Relationships of Imidazole-Coumarin Conjugates against Hepatitis C Virus. AB - A series of new conjugated compounds with a -SCH2- linkage were synthesized by chemical methods from imidazole and coumarin derivatives. The experimental results indicate that of the twenty newly synthesized imidazole-coumarin conjugates, three of them exhibited appealing EC50 values (5.1-8.4 MUM) and selective indices >20 against hepatitis C virus. Their potency and selectivity were increased substantially by modification of their structure with two factors: imidazole nucleus with a hydrogen atom at the N(1) position and coumarin nucleus with a substituent, such as Cl, F, Br, Me, and OMe. These guidelines provide valuable information for further development of conjugated compounds as anti viral agents. PMID- 26901181 TI - Discovery of Uracil Derivatives as Potent Inhibitors of Fatty Acid Amide Hydrolase. AB - Fatty Acid Amide Hydrolase (FAAH) is an intracellular serine enzyme involved in the biological degradation of the fatty acid ethanolamide family of signaling lipids, which exerts neuroprotective, anti-inflammatory, and analgesic properties. In the present study, a conjugated 2,4-dioxo-pyrimidine-1-carboxamide scaffold was confirmed as a novel template for FAAH inhibitors, based on which, a series of analogues had been prepared for an initial structure-activity relationship (SAR) study. Most of the synthesized compounds displayed moderate to significant FAAH inhibitory potency. Among them, compounds 11 and 14 showed better activity than others, with IC50 values of 21 and 53 nM. SAR analysis indicated that 2,4-dioxopyrimidine-1-carboxamides represented a novel class of potent inhibitors of FAAH, and substitution at the uracil ring or replacement of the N-terminal group might favor the inhibitory potency. Selected compounds of this class may be used as useful parent molecules for further investigation. PMID- 26901182 TI - New 3-Cyano-2-Substituted Pyridines Induce Apoptosis in MCF 7 Breast Cancer Cells. AB - The synthesis of new 3-cyano-2-substituted pyridines bearing various pharmacophores and functionalities at position 2 is described. The synthesized compounds were evaluated for their in vitro anti-cancer activities on five cancer cell lines using 5-FU as reference compound. The results revealed that the benzohydrazide derivative 9a induced growth inhibition in human breast cancer cell line MCF-7 with an IC50 value of 2 MUM and it showed lower cytotoxicity on MCF-12a normal breast epithelial cells. Additionally, 9a induced apoptotic morphological changes and induced apoptosis in MCF-7 in a dose and time-dependent manner according to an enzyme linked immunosorbent apoptosis assay which is further confirmed by a TUNEL assay. Flow cytometric analysis indicated that 9a arrested MCF-7 cells in the G1 phase, which was further confirmed by increased expression of p21 and p27 and reduced expression of CDK2 and CDK4. Western blot data revealed significant upregulation of the expression of p53, Bax, caspase-3 and down-regulation of Bcl-2, Mdm-2 and Akt. Additionally, 9a increased the release of cytochrome c from mitochondria to cytoplasm which provokes the mitochondrial apoptotic pathway while it showed no significant change on the expression of the death receptor proteins procaspase-8, caspase-8 and FAS. Furthermore, 9a reduced the expression of phospho AKT and beta-catenin in dose dependent manner while inhibiting the expression of migration-related genes such as matrix metalloproteinase (MMP)-9 and vascular endothelial growth factor (VEGF). Our findings suggest that compound 9a could be considered as a lead structure for further development of more potent apoptosis inducing agents with anti-metastatic activities. PMID- 26901183 TI - Bioadhesive Surfactant Systems for Methotrexate Skin Delivery. AB - Methotrexate (MTX) is an immunosuppressive drug for systemic use in the treatment of skin diseases, however, MTX presents a number of side effects, such as hepatotoxicity. To overcome this limitation, this study developed skin MTX delivery surfactant systems, such as a microemulsion (ME) and a liquid crystalline system (LCS), consisting of a glycol copolymer-based silicone fluid (SFGC) as oil phase, polyether functional siloxane (PFS) as surfactant, and carbomer homopolymer type A (C971) dispersion at 0.5% (wt/wt) as aqueous phase. Polarized light microscopy and small-angle X-ray scattering evidenced the presence of hexagonal and lamellar LCSs, and also a ME. Texture profile and in vitro bioadhesion assays showed that these formulations are suitable for topical application, showing interesting hardness, adhesiveness and compressibility values. Rheology analysis confirmed the Newtonian behaviour of the ME, whereas lamellar and hexagonal LCSs behave as pseudoplastic and dilatant non-Newtonian fluids, respectively. In vitro release profiles indicated that MTX could be released in a controlled manner from all the systems, and the Weibull model showed the highest adjusted coefficient of determination. Finally, the formulations were not cytotoxic to the immortalized human keratinocyte line HaCaT. Therefore, these bioadhesive surfactant systems established with PFS and C971 have great potential as skin delivery systems. PMID- 26901184 TI - Multicomponent Analysis of the Differential Induction of Secondary Metabolite Profiles in Fungal Endophytes. AB - Small molecule histone deacetylase (HDAC) and DNA methyltransferase (DNMT) inhibitors are commonly used to perturb the production of fungal metabolites leading to the induction of the expression of silent biosynthetic pathways. Several reports have described the variable effects observed in natural product profiles in fungi treated with HDAC and DNMT inhibitors, such as enhanced chemical diversity and/or the induction of new molecules previously unknown to be produced by the strain. Fungal endophytes are known to produce a wide variety of secondary metabolites (SMs) involved in their adaptation and survival within higher plants. The plant-microbe interaction may influence the expression of some biosynthetic pathways, otherwise cryptic in these fungi when grown in vitro. The aim of this study was to setup a systematic approach to evaluate and identify the possible effects of HDAC and DNMT inhibitors on the metabolic profiles of wild type fungal endophytes, including the chemical identification and characterization of the most significant SMs induced by these epigenetic modifiers. PMID- 26901185 TI - Influence of Thermal Treatment Conditions on the Properties of Dental Silicate Cements. AB - In this study the sol-gel process was used to synthesize a precursor mixture for the preparation of silicate cement, also called mineral trioxide aggregate (MTA) cement. This mixture was thermally treated under two different conditions (1400 degrees C/2 h and 1450 degrees C/3 h) followed by rapid cooling in air. The resulted material (clinker) was ground for one hour in a laboratory planetary mill (v = 150 rot/min), in order to obtain the MTA cements. The setting time and mechanical properties, in vitro induction of apatite formation by soaking in simulated body fluid (SBF) and cytocompatibility of the MTA cements were assessed in this study. The hardening processes, nature of the reaction products and the microstructural characteristics were also investigated. The anhydrous and hydrated cements were characterized by different techniques e.g., X-ray diffraction (XRD), scanning electron microscopy (SEM), infrared spectroscopy (FT IR) and thermal analysis (DTA-DTG-TG). The setting time of the MTA cement obtained by thermal treatment at 1400 degrees C/2 h (MTA1) was 55 min and 15 min for the MTA cement obtained at 1450 degrees C/3 h (MTA2). The compressive strength values were 18.5 MPa (MTA1) and 22.9 MPa (MTA2). Both MTA cements showed good bioactivity (assessed by an in vitro test), good cytocompatibility and stimulatory effect on the proliferation of cells. PMID- 26901186 TI - Delivery of Flavonoids and Saponins from Black Bean (Phaseolus vulgaris) Seed Coats Incorporated into Whole Wheat Bread. AB - Cereal-based products can be used as vehicles for the delivery of relevant bioactive compounds since they are staple foods for most cultures throughout the world. The health promoting benefits of flavonoids and saponins contained in black bean seed coats have been previously described. In the present work, the effect of adding flavonoids and saponins from black bean seed coat to the typical yeast-leavened whole wheat bread formulation in terms of bread features, organoleptic properties and phytochemical profile was studied. The retention of bioactive compounds was determined and the inhibitory effects of in vitro enzyme digested samples on two colon cancer cell lines (Caco-2 and HT29) was evaluated. The addition of bioactive compounds did not significantly affect baking properties or texture parameters. Among organoleptic properties of enriched breads, only crumb color was affected by the addition of bioactive compounds. However, the use of whole wheat flour partially masked the effect on color. More than 90% of added flavonoids and saponins and 80% of anthocyanins were retained in bread after baking. However, saponins were reduced more than 50% after the in vitro enzyme digestion. The black bean seed coat phytochemicals recovered after in vitro enzyme digestion of enriched breads significantly reduced by 20% the viability of colon cancer cells without affecting standard fibroblast cells (p < 0.05). PMID- 26901187 TI - Therapeutic Effects of Erythroid Differentiation Regulator 1 on Imiquimod-Induced Psoriasis-Like Skin Inflammation. AB - Psoriasis is a common skin disease accompanied by chronic inflammation. In previous studies, erythroid differentiation regulator 1 (ERDR1) was shown to have a negative correlation with proinflammatory cytokine IL-18. However, the role of ERDR1 in the inflammatory skin disease psoriasis has not been evaluated. In this study, to investigate the role of ERDR1 in psoriasis, recombinant ERDR1 was injected intraperitoneally into a psoriasis mouse model. Recombinant ERDR1 (rERDR1) significantly alleviated the symptoms of psoriasis-like skin inflammation and reduced the mRNA of various psoriasis-related markers, including keratin 14, S100A8, and Th17-related cytokines IL-17 and IL-22, suggesting that rERDR1 exerts therapeutic effects on psoriasis via the regulation of Th17 functions. Additionally, the expression of CCL20, a well-known Th17 attracting chemokine, was determined. CCL20 expression significantly decreased in the rERDR1 injected group compared with the vehicle (PBS)-injected group. CCR6 expression in the psoriatic lesional skin was also decreased by rERDR1 administration, implying the inhibition of CCR6-expressing Th17 cell chemotaxis via the downregulation of CCL20. Taken together, this study provides the first evidence that ERDR1 may be a potential therapeutic target for psoriasis. PMID- 26901188 TI - Investigation of the Antiproliferative Properties of Natural Sesquiterpenes from Artemisia asiatica and Onopordum acanthium on HL-60 Cells in Vitro. AB - Plants and plant extracts play a crucial role in the research into novel antineoplastic agents. Four sesquiterpene lactones, artecanin (1), 3beta-chloro 4alpha,10alpha-dihydroxy-1alpha,2alpha-epoxy-5alpha,7alphaH-guaia-11(13)-en 12,6alpha-olide (2), iso-seco-tanapartholide 3-O-methyl ether (3) and 4beta,15 dihydro-3-dehydrozaluzanin C (4), were isolated from two traditionally used Asteraceae species (Onopordum acanthium and Artemisia asiatica). When tested for antiproliferative action on HL-60 leukemia cells, these compounds exhibited reasonable IC50 values in the range 3.6-13.5 MUM. Treatment with the tested compounds resulted in a cell cycle disturbance characterized by increases in the G1 and G2/M populations, while there was a decrease in the S phase. Additionally, 1-3 elicited increases in the hypodiploid (subG1) population. The compounds elicited concentration-dependent chromatin condensation and disruption of the membrane integrity, as revealed by Hoechst 33258-propidium staining. Treatment for 24 h resulted in significant increases in activity of caspases-3 and -9, indicating that the tested sesquiterpenes induced the mitochondrial pathway of apoptosis. The proapoptotic properties of the sesquiterpene lactones were additionally demonstrated withannexin V staining. Compounds 1 and 2 increased the Bax/Bcl-2 expression and decreased the expressions of CDK1 and cyclin B2, as determined at the mRNA level by means of RT-PCR. These experimental results indicate that sesquiterpene lactones may be regarded as potential starting structures for the development of novel anticancer agents. PMID- 26901189 TI - Integrative Transcriptome, Genome and Quantitative Trait Loci Resources Identify Single Nucleotide Polymorphisms in Candidate Genes for Growth Traits in Turbot. AB - Growth traits represent a main goal in aquaculture breeding programs and may be related to adaptive variation in wild fisheries. Integrating quantitative trait loci (QTL) mapping and next generation sequencing can greatly help to identify variation in candidate genes, which can result in marker-assisted selection and better genetic structure information. Turbot is a commercially important flatfish in Europe and China, with available genomic information on QTLs and genome mapping. Muscle and liver RNA-seq from 18 individuals was carried out to obtain gene sequences and markers functionally related to growth, resulting in a total of 20,447 genes and 85,344 single nucleotide polymorphisms (SNPs). Many growth related genes and SNPs were identified and placed in the turbot genome and genetic map to explore their co-localization with growth-QTL markers. Forty-five SNPs on growth-related genes were selected based on QTL co-localization and relevant function for growth traits. Forty-three SNPs were technically feasible and validated in a wild Atlantic population, where 91% were polymorphic. The integration of functional and structural genomic resources in turbot provides a practical approach for QTL mining in this species. Validated SNPs represent a useful set of growth-related gene markers for future association, functional and population studies in this flatfish species. PMID- 26901190 TI - Deep Sequencing and Screening of Differentially Expressed MicroRNAs Related to Milk Fat Metabolism in Bovine Primary Mammary Epithelial Cells. AB - Milk fat is a key factor affecting milk quality and is also a major trait targeted in dairy cow breeding. To determine how the synthesis and the metabolism of lipids in bovine milk is regulated at the miRNA level, primary mammary epithelial cells (pMEC) derived from two Chinese Holstein dairy cows that produced extreme differences in milk fat percentage were cultured by the method of tissue nubbles culture. Small RNA libraries were constructed from each of the two pMEC groups, and Solexa sequencing and bioinformatics analysis were then used to determine the abundance of miRNAs and their differential expression pattern between pMECs. Target genes and functional prediction of differentially expressed miRNAs by Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes analysis illustrated their roles in milk fat metabolism. Results show that a total of 292 known miRNAs and 116 novel miRNAs were detected in both pMECs. Identification of known and novel miRNA candidates demonstrated the feasibility and sensitivity of sequencing at the cellular level. Additionally, 97 miRNAs were significantly differentially expressed between the pMECs. Finally, three miRNAs including bta miR-33a, bta-miR-152 and bta-miR-224 whose predicted target genes were annotated to the pathway of lipid metabolism were screened and verified by real-time qPCR and Western-blotting experiments. This study is the first comparative profiling of the miRNA transcriptome in pMECs that produce different milk fat content. PMID- 26901193 TI - Antinociceptive and Anti-Inflammatory Effects of Zerumbone against Mono Iodoacetate-Induced Arthritis. AB - The fresh rhizome of Zingiber zerumbet Smith (Zingiberaceae) is used as a food flavoring and also serves as a folk medicine as an antipyretic and for analgesics in Taiwan. Zerumbone, a monocyclic sesquiterpene was isolated from the rhizome of Z. zerumbet and is the major active compound. In this study, the anti inflammatory and antinociceptive effects of zerumbone on arthritis were explored using in vitro and in vivo models. Results showed that zerumbone inhibited inducible nitric oxide (NO) synthase (iNOS), cyclooxygenase (COX)-2 expressions, and NO and prostaglandin E2 (PGE2) production, but induced heme oxygenase (HO)-1 expression in a dose-dependent manner in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. When zerumbone was co-treated with an HO-1 inhibitor (tin protoporphyrin (SnPP)), the NO inhibitory effects of zerumbone were recovered. The above results suggest that zerumbone inhibited iNOS and COX-2 through induction of the HO-1 pathway. Moreover, matrix metalloproteinase (MMP)-13 and COX-2 expressions of interleukin (IL)-1beta-stimulated primary rat chondrocytes were inhibited by zerumbone. In an in vivo assay, an acetic acid-induced writhing response in mice was significantly reduced by treatment with zerumbone. Furthermore, zerumbone reduced paw edema and the pain response in a mono iodoacetate (MIA)-induced rat osteoarthritis model. Therefore, we suggest that zerumbone possesses anti-inflammatory and antinociceptive effects which indicate zerumbone could be a potential candidate for osteoarthritis treatment. PMID- 26901192 TI - Systems Pharmacology in Small Molecular Drug Discovery. AB - Drug discovery is a risky, costly and time-consuming process depending on multidisciplinary methods to create safe and effective medicines. Although considerable progress has been made by high-throughput screening methods in drug design, the cost of developing contemporary approved drugs did not match that in the past decade. The major reason is the late-stage clinical failures in Phases II and III because of the complicated interactions between drug-specific, human body and environmental aspects affecting the safety and efficacy of a drug. There is a growing hope that systems-level consideration may provide a new perspective to overcome such current difficulties of drug discovery and development. The systems pharmacology method emerged as a holistic approach and has attracted more and more attention recently. The applications of systems pharmacology not only provide the pharmacodynamic evaluation and target identification of drug molecules, but also give a systems-level of understanding the interaction mechanism between drugs and complex disease. Therefore, the present review is an attempt to introduce how holistic systems pharmacology that integrated in silico ADME/T (i.e., absorption, distribution, metabolism, excretion and toxicity), target fishing and network pharmacology facilitates the discovery of small molecular drugs at the system level. PMID- 26901194 TI - Hinokitiol Inhibits Melanogenesis via AKT/mTOR Signaling in B16F10 Mouse Melanoma Cells. AB - H inokitiol purified from the heartwood of cupressaceous plants has had various biological functions of cell differentiation and growth. Hinokitiol has been demonstrated as having an important role in anti-inflammation and anti-bacteria effect, suggesting that it is potentially useful in therapies for hyperpigmentation. Previously, hinokitiol inhibited the production of melanin by inhibiting tyrosinase activity. The autophagic signaling pathway can induce hypopigmentation. This study is warranted to investigate the mechanism of hinokitiol-induced hypopigmentation through autophagy in B16F10 melanoma cells. The melanin contents and expression of microthphalmia associated transcription factor (MITF) and tyrosinase were inhibited by treatment with hinokitiol. Moreover, the phosphorylation of the protein express levels of phospho-protein kinase B (P-AKT) and phospho-mammalian targets of rapamycin (P-mTOR) were reduced after hinokitiol treatment. In addition, the microtubule associated protein 1 light chain 3 (LC3) -II and beclin 1 (autophagic markers) were increased after the B16F10 cell was treated with hinokitiol. Meanwhile, hinokitiol decreased cellular melanin contents in a dose-dependent manner. These findings establish that hinokitiol inhibited melanogenesis through the AKT/mTOR signaling pathway. PMID- 26901191 TI - The Potential of Plant Phenolics in Prevention and Therapy of Skin Disorders. AB - Phenolic compounds constitute a group of secondary metabolites which have important functions in plants. Besides the beneficial effects on the plant host, phenolic metabolites (polyphenols) exhibit a series of biological properties that influence the human in a health-promoting manner. Evidence suggests that people can benefit from plant phenolics obtained either by the diet or through skin application, because they can alleviate symptoms and inhibit the development of various skin disorders. Due to their natural origin and low toxicity, phenolic compounds are a promising tool in eliminating the causes and effects of skin aging, skin diseases, and skin damage, including wounds and burns. Polyphenols also act protectively and help prevent or attenuate the progression of certain skin disorders, both embarrassing minor problems (e.g., wrinkles, acne) or serious, potentially life-threatening diseases such as cancer. This paper reviews the latest reports on the potential therapy of skin disorders through treatment with phenolic compounds, considering mostly a single specific compound or a combination of compounds in a plant extract. PMID- 26901197 TI - Exploring Architectural Details Through a Wearable Egocentric Vision Device. AB - Augmented user experiences in the cultural heritage domain are in increasing demand by the new digital native tourists of 21st century. In this paper, we propose a novel solution that aims at assisting the visitor during an outdoor tour of a cultural site using the unique first person perspective of wearable cameras. In particular, the approach exploits computer vision techniques to retrieve the details by proposing a robust descriptor based on the covariance of local features. Using a lightweight wearable board, the solution can localize the user with respect to the 3D point cloud of the historical landmark and provide him with information about the details at which he is currently looking. Experimental results validate the method both in terms of accuracy and computational effort. Furthermore, user evaluation based on real-world experiments shows that the proposal is deemed effective in enriching a cultural experience. PMID- 26901195 TI - Energy Metabolism Plays a Critical Role in Stem Cell Maintenance and Differentiation. AB - Various stem cells gradually turned to be critical players in tissue engineering and regenerative medicine therapies. Current evidence has demonstrated that in addition to growth factors and the extracellular matrix, multiple metabolic pathways definitively provide important signals for stem cell self-renewal and differentiation. In this review, we mainly focus on a detailed overview of stem cell metabolism in vitro. In stem cell metabolic biology, the dynamic balance of each type of stem cell can vary according to the properties of each cell type, and they share some common points. Clearly defining the metabolic flux alterations in stem cells may help to shed light on stemness features and differentiation pathways that control the fate of stem cells. PMID- 26901196 TI - Metabolic Activity of Radish Sprouts Derived Isothiocyanates in Drosophila melanogaster. AB - We used Drosophila melanogaster as a model system to study the absorption, metabolism and potential health benefits of plant bioactives derived from radish sprouts (Raphanus sativus cv. Rambo), a Brassicaceae species rich in glucosinolates and other phytochemicals. Flies were subjected to a diet supplemented with lyophilized radish sprouts (10.6 g/L) for 10 days, containing high amounts of glucoraphenin and glucoraphasatin, which can be hydrolyzed by myrosinase to the isothiocyanates sulforaphene and raphasatin, respectively. We demonstrate that Drosophila melanogaster takes up and metabolizes isothiocyanates from radish sprouts through the detection of the metabolite sulforaphane-cysteine in fly homogenates. Moreover, we report a decrease in the glucose content of flies, an upregulation of spargel expression, the Drosophila homolog of the mammalian PPARgamma-coactivator 1 alpha, as well as the inhibition of alpha amylase and alpha-glucosidase in vitro. Overall, we show that the consumption of radish sprouts affects energy metabolism in Drosophila melanogaster which is reflected by lower glucose levels and an increased expression of spargel, a central player in mitochondrial biogenesis. These processes are often affected in chronic diseases associated with aging, including type II diabetes mellitus. PMID- 26901198 TI - Inertial Sensor Error Reduction through Calibration and Sensor Fusion. AB - This paper presents the comparison between cooperative and local Kalman Filters (KF) for estimating the absolute segment angle, under two calibration conditions. A simplified calibration, that can be replicated in most laboratories; and a complex calibration, similar to that applied by commercial vendors. The cooperative filters use information from either all inertial sensors attached to the body, Matricial KF; or use information from the inertial sensors and the potentiometers of an exoskeleton, Markovian KF. A one minute walking trial of a subject walking with a 6-DoF exoskeleton was used to assess the absolute segment angle of the trunk, thigh, shank, and foot. The results indicate that regardless of the segment and filter applied, the more complex calibration always results in a significantly better performance compared to the simplified calibration. The interaction between filter and calibration suggests that when the quality of the calibration is unknown the Markovian KF is recommended. Applying the complex calibration, the Matricial and Markovian KF perform similarly, with average RMSE below 1.22 degrees. Cooperative KFs perform better or at least equally good as Local KF, we therefore recommend to use cooperative KFs instead of local KFs for control or analysis of walking. PMID- 26901200 TI - Classification between Failed Nodes and Left Nodes in Mobile Asset Tracking Systems. AB - Medical asset tracking systems track a medical device with a mobile node and determine its status as either in or out, because it can leave a monitoring area. Due to a failed node, this system may decide that a mobile asset is outside the area, even though it is within the area. In this paper, an efficient classification method is proposed to separate mobile nodes disconnected from a wireless sensor network between nodes with faults and a node that actually has left the monitoring region. The proposed scheme uses two trends extracted from the neighboring nodes of a disconnected mobile node. First is the trend in a series of the neighbor counts; the second is that of the ratios of the boundary nodes included in the neighbors. Based on such trends, the proposed method separates failed nodes from mobile nodes that are disconnected from a wireless sensor network without failures. The proposed method is evaluated using both real data generated from a medical asset tracking system and also using simulations with the network simulator (ns-2). The experimental results show that the proposed method correctly differentiates between failed nodes and nodes that are no longer in the monitoring region, including the cases that the conventional methods fail to detect. PMID- 26901201 TI - An Efficient Virtual Machine Consolidation Scheme for Multimedia Cloud Computing. AB - Cloud computing has innovated the IT industry in recent years, as it can delivery subscription-based services to users in the pay-as-you-go model. Meanwhile, multimedia cloud computing is emerging based on cloud computing to provide a variety of media services on the Internet. However, with the growing popularity of multimedia cloud computing, its large energy consumption cannot only contribute to greenhouse gas emissions, but also result in the rising of cloud users' costs. Therefore, the multimedia cloud providers should try to minimize its energy consumption as much as possible while satisfying the consumers' resource requirements and guaranteeing quality of service (QoS). In this paper, we have proposed a remaining utilization-aware (RUA) algorithm for virtual machine (VM) placement, and a power-aware algorithm (PA) is proposed to find proper hosts to shut down for energy saving. These two algorithms have been combined and applied to cloud data centers for completing the process of VM consolidation. Simulation results have shown that there exists a trade-off between the cloud data center's energy consumption and service-level agreement (SLA) violations. Besides, the RUA algorithm is able to deal with variable workload to prevent hosts from overloading after VM placement and to reduce the SLA violations dramatically. PMID- 26901199 TI - Tunable Microcavity-Stabilized Quantum Cascade Laser for Mid-IR High-Resolution Spectroscopy and Sensing. AB - The need for highly performing and stable methods for mid-IR molecular sensing and metrology pushes towards the development of more and more compact and robust systems. Among the innovative solutions aimed at answering the need for stable mid-IR references are crystalline microresonators, which have recently shown excellent capabilities for frequency stabilization and linewidth narrowing of quantum cascade lasers with compact setups. In this work, we report on the first system for mid-IR high-resolution spectroscopy based on a quantum cascade laser locked to a CaF2 microresonator. Electronic locking narrows the laser linewidth by one order of magnitude and guarantees good stability over long timescales, allowing, at the same time, an easy way for finely tuning the laser frequency over the molecular absorption line. Improvements in terms of resolution and frequency stability of the source are demonstrated by direct sub-Doppler recording of a molecular line. PMID- 26901202 TI - Determination and Visualization of pH Values in Anaerobic Digestion of Water Hyacinth and Rice Straw Mixtures Using Hyperspectral Imaging with Wavelet Transform Denoising and Variable Selection. AB - Biomass energy represents a huge supplement for meeting current energy demands. A hyperspectral imaging system covering the spectral range of 874-1734 nm was used to determine the pH value of anaerobic digestion liquid produced by water hyacinth and rice straw mixtures used for methane production. Wavelet transform (WT) was used to reduce noises of the spectral data. Successive projections algorithm (SPA), random frog (RF) and variable importance in projection (VIP) were used to select 8, 15 and 20 optimal wavelengths for the pH value prediction, respectively. Partial least squares (PLS) and a back propagation neural network (BPNN) were used to build the calibration models on the full spectra and the optimal wavelengths. As a result, BPNN models performed better than the corresponding PLS models, and SPA-BPNN model gave the best performance with a correlation coefficient of prediction (rp) of 0.911 and root mean square error of prediction (RMSEP) of 0.0516. The results indicated the feasibility of using hyperspectral imaging to determine pH values during anaerobic digestion. Furthermore, a distribution map of the pH values was achieved by applying the SPA BPNN model. The results in this study would help to develop an on-line monitoring system for biomass energy producing process by hyperspectral imaging. PMID- 26901203 TI - A Rapid Coordinate Transformation Method Applied in Industrial Robot Calibration Based on Characteristic Line Coincidence. AB - Coordinate transformation plays an indispensable role in industrial measurements, including photogrammetry, geodesy, laser 3-D measurement and robotics. The widely applied methods of coordinate transformation are generally based on solving the equations of point clouds. Despite the high accuracy, this might result in no solution due to the use of ill conditioned matrices. In this paper, a novel coordinate transformation method is proposed, not based on the equation solution but based on the geometric transformation. We construct characteristic lines to represent the coordinate systems. According to the space geometry relation, the characteristic line scan is made to coincide by a series of rotations and translations. The transformation matrix can be obtained using matrix transformation theory. Experiments are designed to compare the proposed method with other methods. The results show that the proposed method has the same high accuracy, but the operation is more convenient and flexible. A multi-sensor combined measurement system is also presented to improve the position accuracy of a robot with the calibration of the robot kinematic parameters. Experimental verification shows that the position accuracy of robot manipulator is improved by 45.8% with the proposed method and robot calibration. PMID- 26901204 TI - One-Pot Hydrothermal Synthesis of Magnetite Prussian Blue Nano-Composites and Their Application to Fabricate Glucose Biosensor. AB - In this work, we presented a simple method to synthesize magnetite Prussian blue nano-composites (Fe3O4-PB) through one-pot hydrothermal process. Subsequently, the obtained nano-composites were used to fabricate a facile and effective glucose biosensor. The obtained nanoparticles were characterized using transmission electron microscopy, scanning electron microscopy, Fourier-transform infrared spectroscopy, UV-vis absorbance spectroscopy, cyclic voltammetry and chronoamperometry. The resultant Fe3O4-PB nanocomposites have magnetic properties which could easily controlled by an external magnetic field and the electro catalysis of hydrogen peroxide. Thus, a glucose biosensor based on Fe3O4-PB was successfully fabricated. The biosensor showed super-electrochemical properties toward glucose detection exhibiting fast response time within 3 to 4 s, low detection limit of 0.5 uM and wide linear range from 5 uM to 1.2 mM with sensitivity of 32 uA?mM(-1)?cm(-2) and good long-term stability. PMID- 26901208 TI - Pollution and Oral Bioaccessibility of Pb in Soils of Villages and Cities with a Long Habitation History. AB - The Dutch cities Utrecht and Wijk bij Duurstede were founded by the Romans around 50 B.C. and the village Fijnaart and Graft-De Rijp around 1600 A.D. The soils of these villages are polluted with Pb (up to ~5000 mg/kg). Lead isotope ratios were used to trace the sources of Pb pollution in the urban soils. In ~75% of the urban soils the source of the Pb pollution was a mixture of glazed potsherd, sherds of glazed roof tiles, building remnants (Pb sheets), metal slag, Pb-based paint flakes and coal ashes. These anthropogenic Pb sources most likely entered the urban soils due to historical smelting activities, renovation and demolition of houses, disposal of coal ashes and raising and fertilization of land with city waste. Since many houses still contain Pb-based building materials, careless renovation or demolition can cause new or more extensive Pb pollution in urban soils. In ~25% of the studied urban topsoils, Pb isotope compositions suggest Pb pollution was caused by incinerator ash and/or gasoline Pb suggesting atmospheric deposition as the major source. The bioaccessible Pb fraction of 14 selected urban soils was determined with an in vitro test and varied from 16% to 82% of total Pb. The bioaccessibility appears related to the chemical composition and grain size of the primary Pb phases and pollution age. Risk assessment based on the in vitro test results imply that risk to children may be underestimated in ~90% of the studied sample sites (13 out of 14). PMID- 26901207 TI - Biosurfactants Produced by Marine Microorganisms with Therapeutic Applications. AB - Marine microorganisms possess unique metabolic and physiological features and are an important source of new biomolecules, such as biosurfactants. Some of these surface-active compounds synthesized by marine microorganisms exhibit antimicrobial, anti-adhesive and anti-biofilm activity against a broad spectrum of human pathogens (including multi-drug resistant pathogens), and could be used instead of existing drugs to treat infections caused by them. In other cases, these biosurfactants show anti-cancer activity, which could be envisaged as an alternative to conventional therapies. However, marine biosurfactants have not been widely explored, mainly due to the difficulties associated with the isolation and growth of their producing microorganisms. Culture-independent techniques (metagenomics) constitute a promising approach to study the genetic resources of otherwise inaccessible marine microorganisms without the requirement of culturing them, and can contribute to the discovery of novel biosurfactants with significant biological activities. This paper reviews the most relevant biosurfactants produced by marine microorganisms with potential therapeutic applications and discusses future perspectives and opportunities to discover novel molecules from marine environments. PMID- 26901205 TI - Cognitive Dysfunction in Major Depressive Disorder. A Translational Review in Animal Models of the Disease. AB - Major Depressive Disorder (MDD) is the most common psychiatric disease, affecting millions of people worldwide. In addition to the well-defined depressive symptoms, patients suffering from MDD consistently complain about cognitive disturbances, significantly exacerbating the burden of this illness. Among cognitive symptoms, impairments in attention, working memory, learning and memory or executive functions are often reported. However, available data about the heterogeneity of MDD patients and magnitude of cognitive symptoms through the different phases of MDD remain difficult to summarize. Thus, the first part of this review briefly overviewed clinical studies, focusing on the cognitive dysfunctions depending on the MDD type. As animal models are essential translational tools for underpinning the mechanisms of cognitive deficits in MDD, the second part of this review synthetized preclinical studies observing cognitive deficits in different rodent models of anxiety/depression. For each cognitive domain, we determined whether deficits could be shared across models. Particularly, we established whether specific stress-related procedures or unspecific criteria (such as species, sex or age) could segregate common cognitive alteration across models. Finally, the role of adult hippocampal neurogenesis in rodents in cognitive dysfunctions during MDD state was also discussed. PMID- 26901209 TI - Metabolic Syndrome and Serum Liver Enzymes in the General Chinese Population. AB - BACKGROUND: The aim of this study was to evaluate the associations between alanine aminotransferase (ALT) and aspartate aminotransferase (AST) with metabolic syndrome (MetS) in the general Chinese population. METHODS: This study was a multicenter, cross-sectional study which was conducted in rural areas of China from the 2012 to 2013 Northeast China Rural Cardiovascular Health Study (NCRCHS), and 11,573 adults with complete data were included in our final analysis. Elevated ALT and AST levels were defined as >40 U/L. Serum ALT and AST levels within the reference range were divided into quartiles, and their associations with MetS were evaluated by logistic regressions. RESULTS: A total of 7.4% and 3.5% participants had elevated serum ALT and AST levels, respectively. The prevalence of MetS was 37.3% in males and 45.8% in females. After adjusting for potential confounders, we found ALT level elevation, even within the reference range, was independently associated with MetS. The odds ratio (OR) values of MetS in the ALT quartiles 2-4 groups within the reference range were 1.113 (95% CI: 1.019-1.280), 1.375 (95% CI: 1.212-1.560), 1.878 (95% CI: 1.650-2.138) compared with the ALT quartile 1 group, and OR in the elevated ALT group was 3.020 (95% CI: 2.496-3.653). Positive relationship for MetS was also observed in elevated AST group (OR: 1.689, 95% CI: 1.314-2.171), but within the reference range, the AST level was not associated with MetS. CONCLUSIONS: Serum ALT level, even within the reference range, was significantly associated with MetS. However, only elevated AST levels above 40 U/L was positively associated with MetS. Within the reference range, we did not find a relationship between AST levels and MetS. PMID- 26901210 TI - Assessment of the Casualty Risk of Multiple Meteorological Hazards in China. AB - A study of the frequency, intensity, and risk of extreme climatic events or natural hazards is important for assessing the impacts of climate change. Many models have been developed to assess the risk of multiple hazards, however, most of the existing approaches can only model the relative levels of risk. This paper reports the development of a method for the quantitative assessment of the risk of multiple hazards based on information diffusion. This method was used to assess the risks of loss of human lives from 11 types of meteorological hazards in China at the prefectural and provincial levels. Risk curves of multiple hazards were obtained for each province and the risks of 10-year, 20-year, 50 year, and 100-year return periods were mapped. The results show that the provinces (municipalities, autonomous regions) in southeastern China are at higher risk of multiple meteorological hazards as a result of their geographical location and topography. The results of this study can be used as references for the management of meteorological disasters in China. The model can be used to quantitatively calculate the risks of casualty, direct economic losses, building collapse, and agricultural losses for any hazards at different spatial scales. PMID- 26901206 TI - Bioactive Compounds Produced by Strains of Penicillium and Talaromyces of Marine Origin. AB - In recent years, the search for novel natural compounds with bioactive properties has received a remarkable boost in view of their possible pharmaceutical exploitation. In this respect the sea is entitled to hold a prominent place, considering the potential of the manifold animals and plants interacting in this ecological context, which becomes even greater when their associated microbes are considered for bioprospecting. This is the case particularly of fungi, which have only recently started to be considered for their fundamental contribution to the biosynthetic potential of other more valued marine organisms. Also in this regard, strains of species which were previously considered typical terrestrial fungi, such as Penicillium and Talaromyces, disclose foreground relevance. This paper offers an overview of data published over the past 25 years concerning the production and biological activities of secondary metabolites of marine strains belonging to these genera, and their relevance as prospective drugs. PMID- 26901211 TI - Environmental Exposure to Triclosan and Semen Quality. AB - Triclosan (2,4,4'-trichloro-2'-hydroxy-diphenyl ether, TCS) is widely used in personal care, household, veterinary and industrial products. It was considered as a potential male reproductive toxicant in previous in vitro and in vivo studies. However, evidence from human studies is scarce. Our study aims to investigate the relationship between TCS exposure and semen quality. We measured urinary TCS concentrations in 471 men recruited from a male reproductive health clinic. TCS was detected in 96.7% of urine samples, with a median concentration of 0.97 ng (mg.creatinine)(-1) (interquartile range, 0.41-2.95 ng (mg.creatinine)(-1)). A multiple linear regression analysis showed a negative association between natural logarithm (Ln) transformed TCS concentration (Ln-TCS) and Ln transformed number of forward moving sperms (adjusted coefficient beta = 0.17; 95% confidence interval (CI) (-0.32, -0.02). Furthermore, among those with the lowest tertile of TCS level, Ln-TCS was negatively associated with the number of forward moving sperms (beta = -0.35; 95% CI (-0.68, -0.03)), percentage of sperms with normal morphology (beta = -1.64; 95% CI (-3.05, -0.23)), as well as number of normal morphological sperms, sperm concentration and count. Our findings suggest that the adverse effect of TCS on semen quality is modest at the environment-relevant dose in humans. Further studies are needed to confirm our findings. PMID- 26901212 TI - Screening for Structural Hemoglobin Variants in Bahia, Brazil. AB - Brazil was the country that received the largest number of Africans during the time of colonization, and Bahia was the Brazilian state that received the largest number of slaves from Africa. The purpose of this study was to evaluate the coverage of the newborn screening program for sickle cell disease in the Reconcavo Baiano region of the state of Bahia, and to show the frequency of the subjects with hemoglobin variants in the 2006-2009 period. Blood samples from neonates in twelve cities in the Reconcavo Baiano region were analyzed by High Performance Liquid Chromatography. A total of 16,402 children were born in this period, 14,773 of which underwent newborn screening. In this period 1416 children were born carrying hemoglobin variants HbS and HbC. Forty-seven patients--20 HbSS genotype and 27 HbSC genotype--were diagnosed in eleven of the twelve cities surveyed. The proportion of children born with sickle cell disease in the Reconcavo Baiano region was 1/314, which was higher than the 1/650 rate for the state of Bahia. The data presented in this study confirm the high frequency of sickle cell disease in Reconcavo Baiano, demonstrating the need to create a referral center for the care of patients with sickle cell diseases in the region. PMID- 26901213 TI - Mental Illness and Juvenile Offenders. AB - Within the past decade, reliance on the juvenile justice system to meet the needs of juvenile offenders with mental health concerns has increased. Due to this tendency, research has been conducted on the effectiveness of various intervention and treatment programs/approaches with varied success. Recent literature suggests that because of interrelated problems involved for youth in the juvenile justice system with mental health issues, a dynamic system of care that extends beyond mere treatment within the juvenile justice system is the most promising. The authors provide a brief overview of the extent to which delinquency and mental illness co-occur; why treatment for these individuals requires a system of care; intervention models; and the juvenile justice systems role in providing mental health services to delinquent youth. Current and future advancements and implications for practitioners are provided. PMID- 26901214 TI - Anthropometric Indices in Adults: Which Is the Best Indicator to Identify Alanine Aminotransferase Levels? AB - BACKGROUND: To evaluate the correlations between serum alanine aminotransferase (ALT) levels and anthropometric indices including body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-to-height ratio (WHtR), waist to-hip ratio (WHR), and a new body index, the A Body Shape Index (ABSI) in Chinese adults. METHODS: A multicenter, cross-sectional study was conducted in rural areas of China in 2012-2013, and 11,331 adults were included in our final analysis. RESULTS: BMI, WC, HC, WHtR, WHR and ABSI were significantly positively correlated with ALT levels. Spearman rank test showed that WHtR (r = 0.346 for men, r = 0.282 for women, both p < 0.001) had the highest correlation coefficient for ALT level, whereas ABSI showed the lowest, and the correlation coefficient of each measure was higher in men than that in women. Comparing the lowest with the highest quintile of each anthropometric measure, the multivariate logistic model presented that WHtR had the superiority of identifying the presence of elevated ALT (OR 4.38; 95% CI 3.15-6.08 for men, OR 4.29; 95% CI 2.91-6.33 for women, both p < 0.001), and the ABSI was the poorest predictor in men (OR 2.51; 95% CI 1.93 3.27, p < 0.001). No association was observed for ABSI in women. CONCLUSIONS: Our results indicated that BMI, WC, HC, WHtR and WHR were able to determine elevated ALT presence, while ABSI was not capable. WHtR and to some extent BMI were the best body indices, for predicting the ALT levels in this population. Nevertheless, the predictive ability of ABSI as a novel body index was not superior compared to established anthropometric indices. PMID- 26901215 TI - Exposure to Agrochemicals and Cardiovascular Disease: A Review. AB - INTRODUCTION: In the agricultural world there is a continuous loss of food, fiber and other commodities due to pests, disease and weeds before harvesting time. These losses had create lots of financial burden to the farm owners that might lead to shutting down of their daily business. Worldwide, there is an overall very high loss of agricultural products due to weeds growth alone. To counteract this problem most farmers resort to the use of agrochemicals to increase their production but compromising the health of their farmworkers. The purpose of the study will be to assess the relationship between the agrochemical particles and cardiovascular diseases among farmworkers. METHOD: Non-systematic review was used to collect data. The following database were use: Medline, EBSCO, and Science Direct to search for the existing journal articles. RESULTS: This study addresses the relationship between agrochemicals particles and cardiovascular diseases in the farming industries using literature review. DISCUSSION: Other researchers had already done an extensive research on the pathway of potential mechanisms linking the ultrafine particulate matter to cardiovascular diseases. The outcomes of those investigations were the clinical results of events that might lead to the development of myocardial infarction, congestive heart failure (CHF), stroke, arrhythmia and sudden death. Xenobiotic compounds that maybe implicated in the pathophysiology of human cardiovascular diseases, will be examined and included in this study. There is compelling evidence suggesting that toxic free radicals of pesticides play an important role in human health. CONCLUSION: There is a close relationship between agrochemicals particle and cardiovascular diseases. PMID- 26901216 TI - The Pathogenesis of Saffold Virus in AG129 Mice and the Effects of Its Truncated L Protein in the Central Nervous System. AB - Saffold Virus (SAFV) is a human cardiovirus that has been suggested to cause severe infection of the central nervous system (CNS). Compared to a similar virus, Theiler's murine encephalomyelitis virus (TMEV), SAFV has a truncated Leader (L) protein, a protein essential in the establishment of persistent CNS infections. In this study, we generated a chimeric SAFV by replacing the L protein of SAFV with that of TMEV. We then compared the replication in cell cultures and pathogenesis in a mouse model. We showed that both SAFV and chimeric SAFV are able to infect Vero and Neuro2a cells well, but only chimeric SAFV was able to infect RAW264.7. We then showed that mice lacking IFN-alpha/beta and IFN gamma receptors provide a good animal model for SAFV infection, and further identified the locality of the infection to the ventral horn of the spine and several locations in the brain. Lastly, we showed that neither SAFV nor chimeric SAFV causes persistence in this model. Overall, our results provide a strong basis on which the mechanisms underlying Saffold virus induced neuropathogenesis can be further studied and, hence, facilitating new information about its pathogenesis. PMID- 26901217 TI - Infectious Salmon Anaemia Virus (ISAV) RNA Binding Protein Encoded by Segment 8 ORF2 and Its Interaction with ISAV and Intracellular Proteins. AB - Infectious salmon anaemia virus (ISAV) is an orthomyxovirus infecting salmonid fish. The virus is adapted to low temperature and has a replication optimum between 10-15 degrees C. In this study the subcellular localization and protein interactions for the protein encoded by the largest open reading frame of gene segment 8 (s8ORF2) were investigated. In ISAV infected cells the s8ORF2 protein was found mainly in the cytosol but a minor fraction of cells expressed the protein in the nucleus as well. Green fluorescent protein-tagged s8ORF2 did not leak out of the cell when the plasma membrane was permeabilized, suggesting interactions with intracellular structural components. The s8ORF2 protein exists both as monomer and homodimer, and co-immunoprecipitation experiments strongly suggests it binds to the ISAV fusion-, nucleo- and matrix proteins. Two versions of s8ORF2 were detected with apparent molecular weights of 24-26 and 35 kDa in lysates of infected cells. The 35 kDa type is an early viral protein while the smaller version appears during the later phases of infection. The 24-26 kDa type was also the predominant form in viral particles. The s8ORF2 protein has previously been shown to bind RNA and interfere with interferon induction and signaling. Here we found that a fraction of the s8ORF2 protein pool in infected cells is likely to be conjugated to the interferon stimulated gene 15 (ISG15) and ubiquitin. Furthermore, several endogenous proteins pulled down by the s8ORF2 protein were identified by liquid chromatography mass spectrometry (LC-MS). PMID- 26901218 TI - Microarray Analysis of Differentially-Expressed Genes Encoding CYP450 and Phase II Drug Metabolizing Enzymes in Psoriasis and Melanoma. AB - Cytochrome P450 drug metabolizing enzymes are implicated in personalized medicine for two main reasons. First, inter-individual variability in CYP3A4 expression is a confounding factor during cancer treatment. Second, inhibition or induction of CYP3A4 can trigger adverse drug-drug interactions. However, inflammation can downregulate CYP3A4 and other drug metabolizing enzymes and lead to altered metabolism of drugs and essential vitamins and lipids. Little is known about effects of inflammation on expression of CYP450 genes controlling drug metabolism in the skin. Therefore, we analyzed seven published microarray datasets, and identified differentially-expressed genes in two inflammatory skin diseases (melanoma and psoriasis). We observed opposite patterns of expression of genes regulating metabolism of specific vitamins and lipids in psoriasis and melanoma samples. Thus, genes controlling the turnover of vitamin D (CYP27B1, CYP24A1), vitamin A (ALDH1A3, AKR1B10), and cholesterol (CYP7B1), were up-regulated in psoriasis, whereas melanomas showed downregulation of genes regulating turnover of vitamin A (AKR1C3), and cholesterol (CYP39A1). Genes controlling abnormal keratinocyte differentiation and epidermal barrier function (CYP4F22, SULT2B1) were up-regulated in psoriasis. The up-regulated CYP24A1, CYP4F22, SULT2B1, and CYP7B1 genes are potential drug targets in psoriatic skin. Both disease samples showed diminished drug metabolizing capacity due to downregulation of the CYP1B1 and CYP3A5 genes. However, melanomas showed greater loss of drug metabolizing capacity due to downregulation of the CYP3A4 gene. PMID- 26901220 TI - Tucum-Do-Cerrado (Bactris setosa Mart.) Consumption Modulates Iron Homeostasis and Prevents Iron-Induced Oxidative Stress in the Rat Liver. AB - This study investigated the effect of tucum-do-cerrado consumption in the oxidative status of iron-supplemented rats. Four groups of rats were treated: Control (AIN-93G), Tuc (AIN-93G added of tucum-do-cerrado), Fe (AIN-93G iron enriched), or TucFe (AIN-93G with tucum-do-cerrado and iron-enriched) diet, for 30 days. Iron-enriched diet increased serum, liver, spleen, and intestine iron levels; transferrin saturation; liver lipid oxidation; mRNA levels of hepatic Hamp and Bmp6, and Nrf2 in the intestine. Tucum-do-cerrado consumption reduced spleen lipid and protein oxidation; mRNA levels of hepatic Hamp and Ftl, and increased serum antioxidant capacity and hepatic mRNA levels of Bmp6, Hmox1, Nqo1, and Nrf2. TucFe diet consumption abrogated the liver Hamp iron-induced up regulation, prevented intestinal iron accumulation; hepatic lipid peroxidation; splenic protein damage, and the increase of catalase, glutathione reductase, and glutathione peroxidase activity in some tissues. These results suggest that tucum do-cerrado protects tissues against oxidative damage, by reducing iron availability in liver and consequently inhibiting liver Hamp expression. PMID- 26901219 TI - Anemia and Micronutrient Status of Women of Childbearing Age and Children 6-59 Months in the Democratic Republic of the Congo. AB - Little is known about the micronutrient status of women and children in the Democratic Republic of the Congo, which is critical for the design of effective nutrition interventions. We recruited 744 mother-child pairs from South Kivu (SK) and Kongo Central (KC). We determined hemoglobin (Hb), serum zinc, vitamin B12, folate, ferritin, soluble transferrin receptor (sTfR), retinol binding protein (RBP), C-reactive protein, and alpha-1 acid glycoprotein concentrations. Anemia prevalence was determined using Hb adjusted for altitude alone and Hb adjusted for both altitude and ethnicity. Anemia prevalence was lower after Hb adjustment for altitude and ethnicity, compared to only altitude, among women (6% vs. 17% in SK; 10% vs. 32% in KC), children 6-23 months (26% vs. 59% in SK; 25% vs. 42% in KC), and children 24-59 months (14% vs. 35% in SK; 23% vs. 44% in KC), respectively. Iron deficiency was seemingly higher with sTfR as compared to inflammation-adjusted ferritin among women (18% vs. 4% in SK; 21% vs. 5% in KC), children 6-23 months (51% vs. 14% in SK; 74% vs. 10% in KC), and children 24-59 months (23% vs. 4% in SK; 58% vs. 1% in KC). Regardless of indicator, iron deficiency anemia (IDA) never exceeded 3% in women. In children, IDA reached almost 20% when sTfR was used but was only 10% with ferritin. Folate, B12, and vitamin A (RBP) deficiencies were all very low (<5%); RBP was 10% in children. The prevalence of anemia was unexpectedly low. Inflammation-adjusted zinc deficiency was high among women (52% in SK; 58% in KC), children 6-23 months (23% in SK; 20% in KC), and children 24-59 months (25% in SK; 27% in KC). The rate of biochemical zinc deficiency among Congolese women and children requires attention. PMID- 26901221 TI - Using NMR-Based Metabolomics to Evaluate Postprandial Urinary Responses Following Consumption of Minimally Processed Wheat Bran or Wheat Aleurone by Men and Women. AB - Wheat bran, and especially wheat aleurone fraction, are concentrated sources of a wide range of components which may contribute to the health benefits associated with higher consumption of whole-grain foods. This study used NMR metabolomics to evaluate urine samples from baseline at one and two hours postprandially, following the consumption of minimally processed bran, aleurone or control by 14 participants (7 Females; 7 Males) in a randomized crossover trial. The methodology discriminated between the urinary responses of control, and bran and aleurone, but not between the two fractions. Compared to control, consumption of aleurone or bran led to significantly and substantially higher urinary concentrations of lactate, alanine, N-acetylaspartate acid and N acetylaspartylglutamate and significantly and substantially lower urinary betaine concentrations at one and two hours postprandially. There were sex related differences in urinary metabolite profiles with generally higher hippurate and citrate and lower betaine in females compared to males. Overall, this postprandial study suggests that acute consumption of bran or aleurone is associated with a number of physiological effects that may impact on energy metabolism and which are consistent with longer term human and animal metabolomic studies that used whole-grain wheat diets or wheat fractions. PMID- 26901222 TI - Beyond Effectiveness--The Adversities of Implementing a Fortification Program. A Case Study on the Quality of Iron Fortification of Fish and Soy Sauce in Cambodia. AB - Fortification of fish and soy sauces is a cost-effective strategy to deliver and increase iron intake in the Cambodian diet, as both are widely consumed by the entire population. In order to qualify as fortified sauces recognized by international regulations, iron content must be between 230 and 460 mg/L, whilst nitrogen and salt should contain no less than 10 g/L and 200 g/L respectively. This survey aims to analyze the progress of the fortification program. Through a better understanding of its obstacles and successes, the paper will then consider approaches to strengthen the program. Two hundred and fifty two samples were collected from 186 plants and 66 markets in various provinces. They were then analyzed for iron, nitrogen and salt content. The study demonstrates that 74% of fortified fish and soy sauces comply with Cambodian regulations on iron content. 87% and 53.6% of the collected samples do not have adequate level of nitrogen and salt content, respectively. The paper will discuss additional efforts that need to be implemented to ensure the sustainability of the project, including the need to: (i) comply with International Codex; (ii) adopt mandatory legislation; and (iii) ensure enforcement. PMID- 26901224 TI - Allomyrina Dichotoma Larvae Regulate Food Intake and Body Weight in High Fat Diet Induced Obese Mice Through mTOR and Mapk Signaling Pathways. AB - Recent evidence has suggested that the Korean horn beetle (Allomyrina dichotoma) has anti-hepatofibrotic, anti-neoplastic, and antibiotic effects and is recognized as a traditional medicine. In our previous works, Allomyrina dichotoma larvae (ADL) inhibited differentiation of adipocytes both in vitro and in vivo. However, the anorexigenic and endoplasmic reticulum(ER) stress-reducing effects of ADL in obesity has not been examined. In this study, we investigated the anorexigenic and ER stress-reducing effects of ADL in the hypothalamus of diet induced obese (DIO) mice. Intracerebroventricular (ICV) administration of ethanol extract of ADL (ADE) suggested that an antagonizing effect on ghrelin-induced feeding behavior through the mTOR and MAPK signaling pathways. Especially, ADE resulted in strong reduction of ER stress both in vitro and in vivo. These findings strongly suggest that ADE and its constituent bioactive compounds are available and valuable to use for treatment of various diseases driven by prolonged ER stress. PMID- 26901225 TI - Association between Genetic Variants in DNA Double-Strand Break Repair Pathways and Risk of Radiation Therapy-Induced Pneumonitis and Esophagitis in Non-Small Cell Lung Cancer. AB - Radiation therapy (RT)-induced pneumonitis and esophagitis are commonly developed side effects in non-small cell lung cancer (NSCLC) patients treated with definitive RT. Identifying patients who are at increased risk for these toxicities would help to maximize treatment efficacy while minimizing toxicities. Here, we systematically investigated single nucleotide polymorphisms (SNPs) within double-strand break (DSB) repair pathway as potential predictive markers for radiation-induced esophagitis and pneumonitis. We genotyped 440 SNPs from 45 genes in DSB repair pathways in 250 stage I-III NSCLC patients who received definitive radiation or chemoradiation therapy, followed by internal validation in 170 additional patients. We found that 11 SNPs for esophagitis and 8 SNPs for pneumonitis showed consistent effects between discovery and validation populations (same direction of OR and reached significance in meta-analysis). Among them, rs7165790 in the BLM gene was significantly associated with decreased risk of esophagitis in both discovery (OR = 0.59, 95% CI: 0.37-0.97, p = 0.037) and validation subgroups (OR = 0.45, 95% CI: 0.22-0.94, p = 0.032). A strong cumulative effect was observed for the top SNPs, and gene-based tests revealed 12 genes significantly associated with esophagitis or pneumonitis. Our results support the notion that genetic variations within DSB repair pathway could influence the risk of developing toxicities following definitive RT in NSCLC. PMID- 26901226 TI - Silent Polymorphisms: Can the tRNA Population Explain Changes in Protein Properties? AB - Silent mutations are being intensively studied. We previously showed that the estrogen receptor alpha Ala87's synonymous polymorphism affects its functional properties. Whereas a link has been clearly established between the effect of silent mutations, tRNA abundance and protein folding in prokaryotes, this connection remains controversial in eukaryotic systems. Although a synonymous polymorphism can affect mRNA structure or the interaction with specific ligands, it seems that the relative frequencies of isoacceptor tRNAs could play a key role in the protein-folding process, possibly through modulation of translation kinetics. Conformational changes could be subtle but enough to cause alterations in solubility, proteolysis profiles, functional parameters or intracellular targeting. Interestingly, recent advances describe dramatic changes in the tRNA population associated with proliferation, differentiation or response to chemical, physical or biological stress. In addition, several reports reveal changes in tRNAs' posttranscriptional modifications in different physiological or pathological conditions. In consequence, since changes in the cell state imply quantitative and/or qualitative changes in the tRNA pool, they could increase the likelihood of protein conformational variants, related to a particular codon usage during translation, with consequences of diverse significance. These observations emphasize the importance of genetic code flexibility in the co translational protein-folding process. PMID- 26901228 TI - Perspective: Adhesion Mediated Signal Transduction in Bacterial Pathogens. AB - During the infection process, pathogenic bacteria undergo large-scale transcriptional changes to promote virulence and increase intrahost survival. While much of this reprogramming occurs in response to changes in chemical environment, such as nutrient availability and pH, there is increasing evidence that adhesion to host-tissue can also trigger signal transduction pathways resulting in differential gene expression. Determining the molecular mechanisms of adhesion-mediated signaling requires disentangling the contributions of chemical and mechanical stimuli. Here we highlight recent work demonstrating that surface attachment drives a transcriptional response in bacterial pathogens, including uropathogenic Escherichia coli (E. coli), and discuss the complexity of experimental design when dissecting the specific role of adhesion-mediated signaling during infection. PMID- 26901227 TI - The Role of Staphylococcus aureus Virulence Factors in Skin Infection and Their Potential as Vaccine Antigens. AB - Staphylococcus aureus (S. aureus) causes the vast majority of skin and soft tissue infections (SSTIs) in humans. S. aureus has become increasingly resistant to antibiotics and there is an urgent need for new strategies to tackle S. aureus infections. Vaccines offer a potential solution to this epidemic of antimicrobial resistance. However, the development of next generation efficacious anti-S. aureus vaccines necessitates a greater understanding of the protective immune response against S. aureus infection. In particular, it will be important to ascertain if distinct immune mechanisms are required to confer protection at distinct anatomical sites. Recent discoveries have highlighted that interleukin 17-producing T cells play a particularly important role in the immune response to S. aureus skin infection and suggest that vaccine strategies to specifically target these types of T cells may be beneficial in the treatment of S. aureus SSTIs. S. aureus expresses a large number of cell wall-anchored (CWA) proteins, which are covalently attached to the cell wall peptidoglycan. The virulence potential of many CWA proteins has been demonstrated in infection models; however, there is a paucity of information regarding their roles during SSTIs. In this review, we highlight potential candidate antigens for vaccines targeted at protection against SSTIs. PMID- 26901223 TI - Docosahexaenoic Acid and Cognition throughout the Lifespan. AB - Docosahexaenoic acid (DHA) is the predominant omega-3 (n-3) polyunsaturated fatty acid (PUFA) found in the brain and can affect neurological function by modulating signal transduction pathways, neurotransmission, neurogenesis, myelination, membrane receptor function, synaptic plasticity, neuroinflammation, membrane integrity and membrane organization. DHA is rapidly accumulated in the brain during gestation and early infancy, and the availability of DHA via transfer from maternal stores impacts the degree of DHA incorporation into neural tissues. The consumption of DHA leads to many positive physiological and behavioral effects, including those on cognition. Advanced cognitive function is uniquely human, and the optimal development and aging of cognitive abilities has profound impacts on quality of life, productivity, and advancement of society in general. However, the modern diet typically lacks appreciable amounts of DHA. Therefore, in modern populations, maintaining optimal levels of DHA in the brain throughout the lifespan likely requires obtaining preformed DHA via dietary or supplemental sources. In this review, we examine the role of DHA in optimal cognition during development, adulthood, and aging with a focus on human evidence and putative mechanisms of action. PMID- 26901229 TI - Factors Influencing the Safety Behavior of German Equestrians: Attitudes towards Protective Equipment and Peer Behaviors. AB - Human interactions with horses entail certain risks. Although the acceptance and use of protective gear is increasing, a high number of incidents and very low or inconsistent voluntary use of safety equipment are reported. While past studies have examined factors influencing the use of safety gear, they have explored neither their influence on the overall safety behavior, nor their relative influence in relation to each other. The aim of the present study is to fill this gap. We conducted an online survey with 2572 participants. By means of a subsequent multiple regression analysis, we explored 23 different variables in view of their influence on the protective behavior of equestrians. In total, we found 17 variables that exerted a significant influence. The results show that both having positive or negative attitudes towards safety products as well as the protective behavior of other horse owners or riding pupils from the stable have the strongest influence on the safety behavior of German equestrians. We consider such knowledge to be important for both scientists and practitioners, such as producers of protective gear or horse sport associations who might alter safety behavior in such a way that the number of horse-related injuries decreases in the long term. PMID- 26901231 TI - Rumination and Rebound from Failure as a Function of Gender and Time on Task. AB - Rumination is a trait response to blocked goals that can have positive or negative outcomes for goal resolution depending on where attention is focused. Whereas "moody brooding" on affective states may be maladaptive, especially for females, "reflective pondering" on concrete strategies for problem solving may be more adaptive. In the context of a challenging general knowledge test, we examined how Brooding and Reflection rumination styles predicted students' subjective and event-related responses (ERPs) to negative feedback, as well as use of this feedback to rebound from failure on a later surprise retest. For females only, Brooding predicted unpleasant feelings after failure as the task progressed. It also predicted enhanced attention to errors through both bottom-up and top-down processes, as indexed by increased early (400-600 ms) and later (600 1000 ms) late positive potentials (LPP), respectively. Reflection, despite increasing females' initial attention to negative feedback (i.e., early LPP), as well as both genders' recurring negative thoughts, did not result in sustained top-down attention (i.e., late LPP) or enhanced negative feelings toward errors. Reflection also facilitated rebound from failure in both genders, although Brooding did not hinder it. Implications of these gender and time-related rumination effects for learning in challenging academic situations are discussed. PMID- 26901230 TI - The Effects of Hypoxia and Inflammation on Synaptic Signaling in the CNS. AB - Normal brain function is highly dependent on oxygen and nutrient supply and when the demand for oxygen exceeds its supply, hypoxia is induced. Acute episodes of hypoxia may cause a depression in synaptic activity in many brain regions, whilst prolonged exposure to hypoxia leads to neuronal cell loss and death. Acute inadequate oxygen supply may cause anaerobic metabolism and increased respiration in an attempt to increase oxygen intake whilst chronic hypoxia may give rise to angiogenesis and erythropoiesis in order to promote oxygen delivery to peripheral tissues. The effects of hypoxia on neuronal tissue are exacerbated by the release of many inflammatory agents from glia and neuronal cells. Cytokines, such as TNF alpha, and IL-1beta are known to be released during the early stages of hypoxia, causing either local or systemic inflammation, which can result in cell death. Another growing body of evidence suggests that inflammation can result in neuroprotection, such as preconditioning to cerebral ischemia, causing ischemic tolerance. In the following review we discuss the effects of acute and chronic hypoxia and the release of pro-inflammatory cytokines on synaptic transmission and plasticity in the central nervous system. Specifically we discuss the effects of the pro-inflammatory agent TNF-alpha during a hypoxic event. PMID- 26901233 TI - Transcriptome Analysis of Cultured Limbal Epithelial Cells on an Intact Amniotic Membrane following Hypothermic Storage in Optisol-GS. AB - The aim of the present study was to investigate the molecular mechanisms underlying activation of cell death pathways using genome-wide transcriptional analysis in human limbal epithelial cell (HLEC) cultures following conventional hypothermic storage in Optisol-GS. Three-week HLEC cultures were stored in Optisol-GS for 2, 4, and 7 days at 4 degrees C. Partek Genomics Suite software v.6.15.0422, (Partec Inc., St. Louis, MO, USA) was used to identify genes that showed significantly different (P < 0.05) levels of expression following hypothermic storage compared to non-stored cell sheets. There were few changes in gene expression after 2 days of storage, but several genes were differently regulated following 4 and 7 days of storage. The histone-coding genes HIST1H3A and HIST4H4 were among the most upregulated genes following 4 and 7 days of hypothermic storage. Bioinformatic analysis suggested that these two genes are involved in a functional network highly associated with cell death, necrosis, and transcription of RNA. HDAC1, encoding histone deacetylase 1, was the most downregulated gene after 7 days of storage. Together with other downregulated genes, it is suggested that HDAC1 is involved in a regulating network significantly associated with cellular function and maintenance, differentiation of cells, and DNA repair. Our data suggest that the upregulated expression of histone-coding genes together with downregulated genes affecting cell differentiation and DNA repair may be responsible for increased cell death following hypothermic storage of cultured HLEC. In summary, our results demonstrated that a higher number of genes changed with increasing storage time. Moreover, in general, larger differences in absolute gene expression values were observed with increasing storage time. Further understanding of these molecular mechanisms is important for optimization of storage technology for limbal epithelial sheets. PMID- 26901234 TI - Pronuclear epigenetic modification of protamine deficient human sperm following injection into mouse oocytes. AB - Epigenetic abnormalities and abnormal chromatin structure in sperm may lead to male infertility. Protamine deficiency is among the disorders of chromatin structure in sperm. The study of epigenetic changes in male pronuclei is necessary since abnormal sperm is sometimes used to create embryos using assisted reproductive techniques. The present study was carried out to compare epigenetic global marks in male pronuclei derived from normal and protamine deficient sperm cells. To do so, interspecies fertilization was used to obtain the male pronucleus. Normal and protamine deficient sperm cells, which were identified by chromomycin A3 staining, were injected into mouse oocytes. Oocytes were cultured until pronuclear formation and were then labeled with different antibodies (anti 5-methylcytosine, anti 5-hydroxymethylcytosine, and anti acetyl H4K12). Based on the fluorescence intensity, the level of each of these epigenetic factors was determined and they revealed a significant relationship between the level of sperm protamine deficiency and sperm epigenetic factors. Protamine deficiency was found to be associated with an increased methylation (p=0) and decreased hydroxymethylation rate (p=0.015) of the male pronucleus chromatin. However, no association was found between protamine deficiency and the level of H4K12 acetylation (p=0.548). Also, the efficiency of fertilization in protamine deficient sperm cells was less than normal. These results suggest that protamine deficient sperm cells lead to the formation of epigenetically altered pronuclei. PMID- 26901232 TI - Homeostatic Signaling by Cell-Cell Junctions and Its Dysregulation during Cancer Progression. AB - The transition of sessile epithelial cells to a migratory, mesenchymal phenotype is essential for metazoan development and tissue repair, but this program is exploited by tumor cells in order to escape the confines of the primary organ site, evade immunosurveillance, and resist chemo-radiation. In addition, epithelial-to-mesenchymal transition (EMT) confers stem-like properties that increase efficiency of colonization of distant organs. This review evaluates the role of cell-cell junctions in suppressing EMT and maintaining a quiescent epithelium. We discuss the conflicting data on junctional signaling in cancer and recent developments that resolve some of these conflicts. We focus on evidence from breast cancer, but include other organ sites where appropriate. Current and potential strategies for inhibition of EMT are discussed. PMID- 26901236 TI - MicroRNA, a new target for engineering new crop cultivars. AB - Global sustainable development depends on, at least partially, the sustainable development of crop reproduction that provides food, cloth and bioenergy as well certain drugs. During thousands of years of human history, many crops have been domesticated for feeding the world. Perfectly, in the past 2 decades, scientists have innovated biotechnological tools for improving crop yield and quality. For sustainable development, more targets and tools are needed to develop. Among these, microRNA (miRNA) is becoming an emerging target for engineering new crop cultivars with high yield and quality as well tolerance to environmental abiotic and biotic stresses. miRNAs are an extensive class of small regulatory RNAs, which play essential roles in all plant biological and metabolic processes, not only in plant development and growth but also in compound biosynthesis and response to various environmental stress. miRNA-based biotechnology is becoming a new strategy for crop improvement, which will play important role in future agricultural sustainable development. PMID- 26901237 TI - Effects of Continuous Peritubal Local Anesthetic Instillation on Postoperative Pain After Percutaneous Nephrolithotomy: A Prospective, Randomized Three-Arm Study. AB - OBJECTIVE: We evaluated the effects of continuous instillation of a local anesthetic at the nephrostomy site on postoperative pain following percutaneous nephrolithotomy (PCNL). PATIENTS AND METHODS: Sixty patients who underwent PCNL between August 2013 and March 2015 were enrolled in this randomized prospective study. The following three groups comprising 20 patients each were analyzed: Group A, continuous infiltration of local anesthetic at the nephrostomy site; Group B, local anesthetic injected only once; and Group C, 0.9% saline injected as a control at the end of the procedure. Postoperative patients reported pain scores, and amount of analgesic use was recorded at 2, 6, 12, 24, and 48 hours after the surgery. RESULTS: The mean pain scores of patients in Group A and B were significantly lower compared with Group C patients as much as 12 hours postoperatively (p = 0.001). However, at 24 hours postoperatively, the mean pain scores of Group B and C patients became comparable, while those of Group A patients remained significantly lower until 48 hours after the surgery (p < 0.001). Patients in Group A and C demanded the least and greatest amounts of analgesics, respectively, at all-time intervals (all p < 0.05). CONCLUSIONS: Continuous infiltration of a local anesthetic is effective for both managing pain immediately after surgery and in dealing with pain that occurs late in the recovery period. PMID- 26901235 TI - Training children's theory-of-mind: A meta-analysis of controlled studies. AB - BACKGROUND: Theory-of-mind (ToM) refers to knowledge and awareness of mental states in oneself and others. Various training programs have been developed to improve ToM in children. OBJECTIVES: In the present study, we conducted a quantitative review of ToM training programs that have been tested in controlled studies. DATA SOURCES: A literature search was conducted using PubMed, PsycInfo, the Cochrane Library, and manual searches. REVIEW METHODS: We identified 32 papers with 45 studies or experiments that included 1529 children with an average age of 63 months (SD=28.7). RESULTS: ToM training procedures were more effective than control procedures and their aggregate effect size was moderately strong (Hedges' g=0.75, CI=0.60-0.89, p<.001). Moderator analyses revealed that although ToM training programs were generally effective, ToM skill-related outcomes increased with length of training sessions and were significantly higher in active control studies. CONCLUSION: ToM training procedures can effectively enhance ToM in children. PMID- 26901238 TI - Descriptive analysis and comparison of two French occupational exposure databases: COLCHIC and SCOLA. AB - BACKGROUND: Several countries have built databases of occupational hygiene measurements. In France, COLCHIC and SCOLA co-exist, started in 1987 and 2007, respectively. METHODS: A descriptive comparison of the content of the two databases was carried out during the period 1987-2012, including variables, workplaces and agents, as well as exposure levels. RESULTS: COLCHIC and SCOLA contain, respectively, 841,682 (670 chemicals) and 152,486 records (70). They cover similar industries and occupations, and contain the same ancillary information. Across 17 common agents with >500 samples, the ratio of the median concentration in COLCHIC to the median concentration in SCOLA was 3.45 [1.03 14.3] during 2007-2012. This pattern remained when stratified by industry, task, and occupation, but was attenuated when restricted to similar sampling duration. CONCLUSIONS: COLCHIC and SCOLA represent a considerable source of information, but result from different purposes (prevention, regulatory). Potential differences due to strategies should evaluated when interpreting data from these databases. PMID- 26901239 TI - Uncommon secondary metabolites from Etlingera pavieana rhizomes. AB - From the rhizomes of Etlingera pavieana (Pierre ex Gagnep.) R.M. Sm., four phenylpropens, (E)-3-(4-methoxyphenyl)prop-2-en-1-amine (1), (E)-4 methoxycinamaldehyde (2), (E)-4-methoxycinamic acid (3) and (E)-1-methoxy-4-(3 methoxyprop-1-enyl)benzene (4), together with two other compounds, (E)-((E)-3-(4 methoxyphenyl)allyl)3-(4-hydroxyphenyl)acrylate (5) and 4-methoxybenzoic acid (6) were isolated. This is the first report on the presence of all compounds in Etlingera. Compounds 1 and 5 have been previously synthesised, but this is the first report of their isolation from a natural source. Compound 5 exhibited weak activity against Mycobacterium tuberculosis with MIC 50.00 MUg/mL and cytotoxic activity against the KB, MCF7 and NCI-H187 cells with IC50 values of 25.11, 20.16 and 34.83 MUg/mL, respectively. PMID- 26901240 TI - Effects of temperature during the irradiation of calcium carbonate. AB - Calcium carbonate received gamma irradiation at different doses (0-309kGy) and temperature regimes (77-298K) to study the effects of irradiation temperature. The changes were followed by EPR spectroscopy. We observed the formation of a composite EPR spectrum, even at low radiation doses and temperature. There was a strong effect on the evaluation of the radicals formed as a function of irradiation temperature, probably due to the diffusion in the frozen powder and the recombination of some radicals at room temperature. PMID- 26901242 TI - Nonlinear Resistance Training Enhances the Lipid Profile and Reduces Inflammation Marker in People Living With HIV: A Randomized Clinical Trial. AB - BACKGROUND: Highly active antiretroviral therapy (HAART) is associated with high total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), triglyceride (TG), and C-reactive protein (CRP) levels. The natural course of the HIV infection reduces the high-density lipoprotein level (HDL-c). Thus, physical exercise plays a key role in reducing the effects of HAART and HIV. METHODS: Thirty people living with HIV (PLHIV) were randomized to the nonlinear resistance training (NLRT) and control (CON) groups. The NLRT group underwent 12 weeks of resistance training, whereas the CON group maintained usual daily activities. All volunteers underwent anthropometric, body composition, and biochemical assessments at the beginning and end of 12 weeks. RESULTS: After 12 weeks, the NLRT group had increased lean body mass (P < .0001), and a reduction in body fat mass (P < .0001) and body fat percentage (P < .0001). The levels of TC (P < .0001), LDL-c (P = .049), TG (P < .0001), and CRP (P = .004) were reduced, and the HDL-c level increased (P < .0001). CONCLUSION: Twelve weeks of NLRT causes beneficial changes in the body composition, lipid profile, and inflammation markers in PLHIV, and it can be used in this patient population. PMID- 26901243 TI - Multiple phonetically trained-listener comparisons of speech before and after articulatory intervention in two children with repaired submucous cleft palate. AB - Cleft Palate (CP) assessments based on phonetic transcription are the "gold standard" therapy outcome measure, despite reliability difficulties. Here we propose a novel perceptual evaluation, applied to ultrasound-visual biofeedback (U-VBF) therapy and therapy using visual articulatory models (VAMs) for two children with repaired submucous CP. Three comparisons were made: post VAM, post U-VBF and overall pre- and post-therapy. Twenty-two phonetically-trained listeners were asked to determine whether pre- or post-therapy recordings sounded "closer to the English target", using their own implicit phonological knowledge (prompted via orthographic representation). Results are compared with segment oriented percent target consonant correct (PTCC) derived from phonetic transcriptions. Listener judgements and PTCC suggest that both children made improvements using both VAM and U-VBF. Statistical analysis showed listener agreement in each comparison, though agreement was weak. However, perceptual evaluation offers a straightforward method of evaluating the effectiveness of interventions and can be used by phonetically trained or lay listeners. PMID- 26901241 TI - Genetic association of TLR4 Asp299Gly, TLR4 Thr399Ile, and CD14 C-159T polymorphisms with the risk of severe RSV infection: a meta-analysis. AB - Respiratory syncytial virus (RSV) is the most frequent cause of hospitalization in infants worldwide. It is recognized by Toll-like receptor 4 (TLR 4) and cluster of differentiation 14 (CD14) in the innate immune response. Previous case control studies reported the influence of TLR4 Asp299Gly, TLR4 Thr399Ile, and CD14 C-159T polymorphisms on the risk of severe RSV infection. However, a decisive conclusion has not been achieved. Therefore, we performed this meta analysis to examine the association between these three polymorphisms and the development of RSV bronchiolitis. A systematic literature search was performed using the PubMed, EMbase, Google Scholar Search, China National Knowledge Infrastructure, China Biological Medicine, and Wanfang Databases. The data were extracted and pooled odds ratios with 95% confidence intervals were calculated under six genetic models. A total of six studies with 1009 cases and 1348 controls, three studies with 473 cases and 481 controls, or four studies with 325 cases and 650 controls relating to each of the three polymorphisms were included in this meta-analysis. The analyzed data indicated that all of these polymorphisms were not associated with the risk of severe RSV infection. This is the first meta-analysis to investigate the relationship of TLR4 Asp299Gly, TLR4 Thr399Ile, and CD14 C-159T polymorphisms with the risk of severe RSV infection. Although the results of this retrospective analysis indicated a lack of the association, more extensive multicentric studies with large sample sizes are necessary to provide a more reliable estimation of the association between these three polymorphisms and RSV bronchiolitis susceptibility. PMID- 26901245 TI - Tetrachlorobenzoquinone Stimulates NLRP3 Inflammasome-Mediated Post-Translational Activation and Secretion of IL-1beta in the HUVEC Endothelial Cell Line. AB - Our previous studies suggested that tetrachlorobenzoquinone (TCBQ) elicits pro inflammatory activities; however, the mechanism of its toxicity toward vascular endothelial cell has not been characterized. Although TCBQ has been shown to stimulate interleukin-1 beta (IL-1beta) expression, it is unknown whether TCBQ regulates post-translational IL-1beta activation. Using human umbilical vein endothelial cells, we discovered that TCBQ not only promotes the expression of NOD-like receptor family, pyrin domain-containing protein 3 (NLRP3) components [composed of NLRP3, adaptor molecule apoptosis-associated speck like protein containing a caspase activation and recruitment domain (ASC), and pro-caspase 1] but also participates in priming the NLRP3 inflammasome. Activation of the NLRP3 inflammasome results in the maturation and release of IL-1beta. Further experiments showed that K(+) efflux, reactive oxygen species (ROS) production, and mitochondrial DNA damage may be involved in NLRP3 inflammasome activation mediated by TCBQ. Moreover, TCBQ downregulates the ubiquitination of NLRP3, further facilitating the activation of the NLRP3 inflammasome. These results suggest that the NLRP3/IL-1beta signaling pathway plays an important role in TCBQ induced endothelial cell pro-inflammatory responses, which may point to potential therapeutic approaches against TCBQ-mediated toxicity. PMID- 26901244 TI - A multistage mycobacterium tuberculosis subunit vaccine LT70 including latency antigen Rv2626c induces long-term protection against tuberculosis. AB - To develop an effective subunit vaccine which could target tubercle bacilli with different metabolic states and provide effective protective immunity, we fused antigens ESAT6, Ag85B, peptide 190-198 of MPT64, and Mtb8.4 mainly expressed by proliferating bacteria and latency-associated antigen Rv2626c together to construct a multistage protein ESAT6-Ag85B-MPT64(190-198)-Mtb8.4-Rv2626c (LT70 for short) with the molecular weight of 70 kDa. The human T-cell responses to LT70 and other antigens were analyzed. The immune responses of LT70 in the adjuvant of DDA and Poly I:C and its protective efficacy against Mycobacterium tuberculosis (M. tuberculosis) infection in C57BL/6 mice were evaluated. The results showed that LT70 was stably produced in Escherichia coli and could be purified by successive salting-out and chromatography. LT70 could be strongly recognized by human T cells from TB patients and persons who are supposed latently infected with M. tuberculosis. The subunit vaccine LT70 generated strong antigen-specific humoral and cell-mediated immunity, and induced higher protective efficacy (5.41+/-0.37 Log10 CFU in lung) than traditional vaccine Bacillus Calmette-Guerin (6.01+/-0.33 Log10 CFU) and PBS control (6.53+/-0.26 Log10 CFU) at 30 weeks post vaccination (10 weeks post-challenge) against M. tuberculosis infection (p < 0.05). These findings suggested that LT70 would be a promising subunit vaccine candidate against M. tuberculosis infection. PMID- 26901249 TI - A single-center retrospective analysis of first-line therapy of multiple myeloma with bendamustine-bortezomib-dexamethasone. AB - The aim of this retrospective study was to evaluate the efficacy and toxicity profile of bendamustine, bortezomib, and dexamethasone (BBD) combination treatment of patients with newly diagnosed multiple myeloma (MM). BBD treatment had a response rate of 80% regarding patients with >= partial response (PR). Median time to best response was 87.5 days and PFS was 22 months. Median of OS was not reached. PFS of non-responding patients was significantly shortened compared to those with >= PR. No statistically significant differences were determined concerning age (>= vs. < 68 years) and ISS stage (ISS stage I/II vs. III). Grade 3 hematological effects and grade 3/4 non-hematological effects occurred in 20% and 35% of patients, respectively. Most pronounced hematological adverse event was leukopenia, the most severe non-hematological ones affected the cardiovascular system. In summary, BBD treatment was of acceptable efficacy in patients with newly diagnosed MM and exhibited rather low toxicity. PMID- 26901250 TI - Mortality atlas of the main causes of death in Switzerland, 2008-2012. AB - PRINCIPLES: Analysis of the spatial distribution of mortality data is important for identification of high-risk areas, which in turn might guide prevention, and modify behaviour and health resources allocation. This study aimed to update the Swiss mortality atlas by analysing recent data using Bayesian statistical methods. We present average pattern for the major causes of death in Switzerland. METHODS: We analysed Swiss mortality data from death certificates for the period 2008-2012. Bayesian conditional autoregressive models were employed to smooth the standardised mortality rates and assess average patterns. Additionally, we developed models for age- and gender-specific sub-groups that account for urbanisation and linguistic areas in order to assess their effects on the different sub-groups. RESULTS: We describe the spatial pattern of the major causes of death that occurred in Switzerland between 2008 and 2012, namely 4 cardiovascular diseases, 10 different kinds of cancer, 2 external causes of death, as well as chronic respiratory diseases, Alzheimer's disease, diabetes, influenza and pneumonia, and liver diseases. In-depth analysis of age- and gender specific mortality rates revealed significant disparities between urbanisation and linguistic areas. CONCLUSIONS: We provide a contemporary overview of the spatial distribution of the main causes of death in Switzerland. Our estimates and maps can help future research to deepen our understanding of the spatial variation of major causes of death in Switzerland, which in turn is crucial for targeting preventive measures, changing behaviours and a more cost-effective allocation of health resources. PMID- 26901252 TI - [The BRIDGE study]. PMID- 26901253 TI - [Futility in Cardiology]. AB - Medical futility refers to interventions that are unlikely to produce any significant benefit for the patient. Medical and technological resources allow many patients affected by advanced cardiovascular diseases to receive more aggressive and expensive treatments than ever before. This wide range of available options can frequently lead to the delay of complex end-of-life decisions, such as starting palliative care programs. Medical futility is a daily problem, with significant ethical implications and concerns about the respect of the main ethics points: non maleficence, patient's autonomy, and justice. This paper examines some considerations and applications of the concept of medical futility, particularly about the various definitions of futility, the complexities of management when care is considered futile and the ethical and clinical criteria to withdrawing or withholding aggressive treatments. The patient-centered care, based on physician-patient communication, seems to be the best approach to this problem, even with a patient with advanced heart disease. Finally, the increasing power of technology and its relationship with the current cultural values of the developed societies are outlined, particularly when end-of life decisions are addressed. PMID- 26901251 TI - Perceptual Learning of Intonation Contour Categories in Adults and 9- to 11-Year Old Children: Adults Are More Narrow-Minded. AB - We report on rapid perceptual learning of intonation contour categories in adults and 9- to 11-year-old children. Intonation contours are temporally extended patterns, whose perception requires temporal integration and therefore poses significant working memory challenges. Both children and adults form relatively abstract representations of intonation contours: Previously encountered and novel exemplars are categorized together equally often, as long as distance from the prototype is controlled. However, age-related differences in categorization performance also exist. Given the same experience, adults form narrower categories than children. In addition, adults pay more attention to the end of the contour, while children appear to pay equal attention to the beginning and the end. The age range we examine appears to capture the tail-end of the developmental trajectory for learning intonation contour categories: There is a continuous effect of age on category breadth within the child group, but the oldest children (older than 10;3) are adult-like. PMID- 26901254 TI - [The relationship between gut microbiota and cardiovascular diseases]. AB - The prevalence of cardiometabolic disorders (obesity, type 2 diabetes and cardiovascular disorders) is increasing globally and is a leading cause of mortality worldwide. Both genetics and environmental factors are involved in the pathogenesis of these disorders. Recent studies have shown that a state of dysbiosis may be implicated in body weight control, insulin resistance and cardio metabolic risk factors, but the underlying mechanisms remain to be fully understood. Here we describe the possible role of the gut microbiota in cardiovascular diseases. PMID- 26901255 TI - [Dilated cardiomyopathy: a dynamic disease - clinical course, reverse remodeling and prognostic stratification]. AB - Dilated cardiomyopathy (DCM) is a relatively rare primary heart muscle disease with genetic or post-inflammatory etiology. In the last decade, the incidence and prevalence of the disease have significantly increased as a consequence of an earlier diagnosis supported by extensive familial screening programs and by the improvement in diagnostic techniques. Moreover, current therapeutic strategies have deeply modified the prognosis of DCM with a dramatic reduction in mortality. A significant number of patients with DCM present an impressive response to pharmacological and non-pharmacological therapy in terms of left ventricular reverse remodeling (reduction in ventricular size with improvement of systolic function), which confers a more favorable prognosis in the long term. However, the identification of patients with an increased likelihood of improvement after therapeutic optimization remains a challenging issue; in particular the assessment of arrhythmic risk carries important implications. Finally, the long term follow-up of patients showing a significant left ventricular functional recovery under optimal treatment is still poorly known. Hence, the aim of the present review is to provide an insight into the clinical evolution/long-term follow-up of DCM, which should be actually considered a dynamic process rather than a static and chronic disease. Left ventricular reverse remodeling should be considered a key therapeutic goal, mostly associated with a long-standing recovery, but cannot be considered the expression of permanent "healing", confirming the need for a systematic and careful follow-up over time in this setting. PMID- 26901256 TI - [Echocardiography for the evaluation of patients with heart failure]. AB - Echocardiography is the most widely used technique for evaluating patients with heart failure owing to its widespread use, non-invasiveness and ability to provide diagnostic, functional, hemodynamic and prognostic information. However, echocardiography is not always used appropriately as regards both clinical indications to the examination and the information gathered in the course of the examination itself. This can lead to repeated, unnecessary or unhelpful echocardiographic evaluations, that is, non-optimal consumption of available resources. The purpose of this article is to describe how to use echocardiography appropriately for assessing patients with heart failure, and to highlight the advantages and limitations of this technique. PMID- 26901258 TI - [A national campaign for the promotion of the appropriate use of natriuretic peptide assays in heart failure patients]. PMID- 26901257 TI - [Natriuretic peptides for the management of patients with heart failure: a bridge between primary care and cardiology?]. AB - BACKGROUND: The increasing prevalence of heart failure (HF) mandates the establishment of shared strategies between primary care physicians (PCP) and cardiologists to offer patients continuity of care. Easily available, low-cost biomarkers hold potential to facilitate this process. Data on the diffusion of natriuretic peptides (NP), a major novelty in the HF field in the last decade, in primary care are scarce. METHODS: The Cardiovascular Area of the Italian General Practice Society led a web survey among its members to investigate knowledge, perceptions and use of NP for HF management among Italian PCP. RESULTS: Over 700 PCP took part in the survey, three out of four declared they never or only occasionally prescribed NP assays. Among participating PCP, 86% reported that PN values were not regularly mentioned in discharge summaries of their patients hospitalized for acute HF. Conversely, only 4% reported to receive regularly PN prescription by cardiologists for their outpatients with chronic HF. One of five respondents ignored whether the assay was reimbursed by the National Health Service. The high negative predictive value for HF of elevated NP levels, the strongest evidence-based indication of NP, was correctly pointed out only by 13% of PCP. CONCLUSIONS: In our PCP sample, we documented a marginal use of NP in the management of HF patients. This is likely, at least in part, linked to a perceived scarce indication of NP values in discharge summaries and limited prescription in HF outpatients by cardiologists. Overall, PCP knowledge of the evidence on NP assay use for diagnosis, risk stratification and guided therapy of HF was limited. Two expert cardiologists were asked to comment on these findings and on the controversial aspects of the current use of NP in HF patients to better define their role as a tool for shared care between cardiologists and PCP. PMID- 26901259 TI - [Strategies for reducing door to balloon time in patients with acute myocardial infarction undergoing primary angioplasty: the Pavia experience]. AB - BACKGROUND: Primary percutaneous coronary intervention (pPCI) is the treatment of choice in patients with ST-elevation myocardial infarction (STEMI) if performed by an experienced team within 120 min of first medical contact. The door to balloon time (DTB) has become a performance measure and is the focus of local, regional and national quality improvement initiatives. The primary objective of the present study was to evaluate whether the implementation of reperfusion strategies could result in shorter DTB times. METHODS: In 2007, at the cath lab of the IRCCS Policlinico San Matteo (a hub of a network including 7 spoke centers), 245 pPCI were performed with a median DTB time of 116 (25th-75th percentile, 96-155) min, and <90 min only in 20% of cases. To improve time to reperfusion, the following strategies were adopted in 2010 and 2011: direct access to the cath lab without initial coronary care unit admission; activation of the cath lab based on pre-hospital ECG; a faster triage with ECG performed within 10 min and use of a dedicated ambulance for patients presenting directly to the emergency room (ER) of the hub. RESULTS: Overall, 226 and 258 pPCI were performed in 2010 and 2011, respectively, with no differences in type of hospital admission (emergency medical service, ER, or spoke) compared with 2007. A significant DTB reduction was observed (2007 vs 2010 vs 2011: 116 [96-155] vs 99 [77-129] vs 97 [80-125] min, p<0.0001), with a significant improvement in the number of patients treated within 90 min (20 vs 41 vs 40%, p<0.0001) as a result of a significant reduction in the time from first medical contact to cath lab (86 [64-124] vs 66 [50-93] vs 62 [46-93] min, p<0.0001). By analyzing only data from 2010 and 2011, median DTB was 88 (73-104) min for patients arriving through the emergency medical service, 139 (116-179) min for patients presenting to spoke centers, and 96 (75-126) min for patients presenting to the ER, with pPCI performed within 90 min in 55%, 8% e 42% of cases, respectively. The longer DTB time of the spoke centers was solely due to transportation to the hub (emergency medical service vs spoke: 56 [42-68] vs 106 [86-147] min, p<0.0001), with no differences in time to reperfusion once the cath lab was reached. CONCLUSIONS: Based on our strategies and experience including 729 STEMI patients treated with pPCI in 2007, 2010 and 2011, a significant improvement in DTB time was achieved. The main factor affecting our results is transportation to the cath lab for patients with direct access to spoke centers. Further exploration and advocacy for DTB implementation in these patients are warranted. PMID- 26901260 TI - [A rare cause of dyspnea on exertion]. AB - Vascular rings are rare anomalies accounting for 1% to 3% of all congenital heart diseases with a similar frequency in both sexes, which can result in a variable degree of extrinsic compression of the trachea and esophagus. We report the case of a 46-year-old woman with symptomatic dyspnea and double aortic arch that caused esophageal tracheal compression. Considering the little impact of the functional vascular anomaly in our case, a conservative approach was adopted with clinical and functional annual follow-up. PMID- 26901261 TI - [Pulmonary stenosis and atrial septal defect: a rare association in the elderly]. AB - We report the case of an elderly woman with persistent unrepaired atrial septal defect and moderate pulmonary stenosis. The diagnostic work-up and the echocardiographic findings of such a rare case are reported, along with a brief description of heart failure pathophysiology in this grown-up congenital heart disease.To the best of our knowledge, this is the first case with the greater longevity in an elderly patient with unrepaired atrial septal defect and pulmonary stenosis ever reported in the literature. PMID- 26901262 TI - [Position paper of the Italian Society of Interventional Cardiology (SICI-GISE): antithrombotic therapy in elderly patients with acute coronary syndrome]. AB - With the ageing of the population in the Western world, an increasing proportion of patients seen in cardiology practice is represented by the elderly. Although approximately one third of patients admitted with acute coronary syndrome (ACS) are >75 years old and the mortality rate in this age group is doubled compared with younger patients, this population is underrepresented in randomized controlled trials and, consequently, clinical guidelines do not always provide clear indications for the management of elderly patients. Therefore, there is an unmet need for clinical guidance regarding this rapidly growing subset of ACS patients, also considering that decisions about optimal antithrombotic treatment strategies in the elderly are often challenging, mostly due to age-related organ dysfunction, the frequency of comorbidities and concomitant medications and an increased risk of both ischemic and bleeding events. A panel of Italian cardiology experts assembled under the auspices of the Italian Society of Interventional Cardiology (SICI-GISE) for comprehensive discussion and consensus development, with the aim to provide practical recommendations, for both clinical and interventional cardiologists, regarding optimal management of antithrombotic therapy in patients with ACS aged >=75 years. In this position paper, various clinical scenarios in patients with ST-elevation and non-ST-elevation myocardial infarction or unstable angina are presented and discussed, including special subsets (e.g., patients aged >=85 years, patients with chronic renal disease or previous cerebrovascular events, patients requiring triple therapy or long-term antithrombotic therapy), with the panel's recommendations being provided for each scenario. PMID- 26901263 TI - A Randomized Control Trial: Supplementing Hearing Aid Use with Listening and Communication Enhancement (LACE) Auditory Training. AB - OBJECTIVE: To examine the effectiveness of the Listening and Communication Enhancement (LACE) program as a supplement to standard-of-care hearing aid intervention in a Veteran population. DESIGN: A multisite randomized controlled trial was conducted to compare outcomes following standard-of-care hearing aid intervention supplemented with (1) LACE training using the 10-session DVD format, (2) LACE training using the 20-session computer-based format, (3) placebo auditory training (AT) consisting of actively listening to 10 hr of digitized books on a computer, and (4) educational counseling-the control group. The study involved 3 VA sites and enrolled 279 veterans. Both new and experienced hearing aid users participated to determine if outcomes differed as a function of hearing aid user status. Data for five behavioral and two self-report measures were collected during three research visits: baseline, immediately following the intervention period, and at 6 months postintervention. The five behavioral measures were selected to determine whether the perceptual and cognitive skills targeted in LACE training generalized to untrained tasks that required similar underlying skills. The two self-report measures were completed to determine whether the training resulted in a lessening of activity limitations and participation restrictions. Outcomes were obtained from 263 participants immediately following the intervention period and from 243 participants 6 months postintervention. Analyses of covariance comparing performance on each outcome measure separately were conducted using intervention and hearing aid user status as between-subject factors, visit as a within-subject factor, and baseline performance as a covariate. RESULTS: No statistically significant main effects or interactions were found for the use of LACE on any outcome measure. CONCLUSIONS: Findings from this randomized controlled trial show that LACE training does not result in improved outcomes over standard-of-care hearing aid intervention alone. Potential benefits of AT may be different than those assessed by the performance and self-report measures utilized here. Individual differences not assessed in this study should be examined to evaluate whether AT with LACE has any benefits for particular individuals. Clinically, these findings suggest that audiologists may want to temper the expectations of their patients who embark on LACE training. PMID- 26901265 TI - First-principles molecular dynamics simulation of the Ca2UO2(CO3)3 complex in water. AB - Recent experiments have shown that the neutral Ca2UO2(CO3)3 complex is the dominant species of uranium in many uranyl-containing streams. However, the structure and solvation of such a species in water has not been investigated from first principles. Herein we present a first principles molecular dynamics perspective of the Ca2UO2(CO3)3 complex in water based on density functional theory and Born-Oppenheimer approximation. We find that the Ca2UO2(CO3)3 complex is very stable in our simulation timeframe for three different concentrations considered and that the key distances from our simulation are in good agreement with the experimental data from extended X-ray absorption fine structure (EXAFS) spectroscopy. More important, we find that the two Ca ions bind differently in the complex, as a result of the hydrogen-bonding network around the whole complex. This finding invites confirmation from time-resolved EXAFS and has implications in understanding the dissociative equilibrium of the Ca2UO2(CO3)3 complex in water. PMID- 26901264 TI - The Effects of Acoustic Bandwidth on Simulated Bimodal Benefit in Children and Adults with Normal Hearing. AB - OBJECTIVES: The primary purpose of this study was to examine the effect of acoustic bandwidth on bimodal benefit for speech recognition in normal-hearing children with a cochlear implant (CI) simulation in one ear and low-pass filtered stimuli in the contralateral ear. The effect of acoustic bandwidth on bimodal benefit in children was compared with the pattern of adults with normal hearing. Our hypothesis was that children would require a wider acoustic bandwidth than adults to (1) derive bimodal benefit, and (2) obtain asymptotic bimodal benefit. DESIGN: Nineteen children (6 to 12 years) and 10 adults with normal hearing participated in the study. Speech recognition was assessed via recorded sentences presented in a 20-talker babble. The AzBio female-talker sentences were used for the adults and the pediatric AzBio sentences (BabyBio) were used for the children. A CI simulation was presented to the right ear and low-pass filtered stimuli were presented to the left ear with the following cutoff frequencies: 250, 500, 750, 1000, and 1500 Hz. RESULTS: The primary findings were (1) adults achieved higher performance than children when presented with only low-pass filtered acoustic stimuli, (2) adults and children performed similarly in all the simulated CI and bimodal conditions, (3) children gained significant bimodal benefit with the addition of low-pass filtered speech at 250 Hz, and (4) unlike previous studies completed with adult bimodal patients, adults and children with normal hearing gained additional significant bimodal benefit with cutoff frequencies up to 1500 Hz with most of the additional benefit gained with energy below 750 Hz. CONCLUSIONS: Acoustic bandwidth effects on simulated bimodal benefit were similar in children and adults with normal hearing. Should the current results generalize to children with CIs, these results suggest pediatric CI recipients may derive significant benefit from minimal acoustic hearing (<250 Hz) in the nonimplanted ear and increasing benefit with broader bandwidth. Knowledge of the effect of acoustic bandwidth on bimodal benefit in children may help direct clinical decisions regarding a second CI, continued bimodal hearing, and even optimizing acoustic amplification for the nonimplanted ear. PMID- 26901266 TI - Characterizing the Adsorption of Poly(vinyl alcohol) on Colloidal Silica with Aggregation-Induced Emission Fluorophore. AB - The adsorption of polymer on colloidal particle has significant influence on colloid structure and dynamics. Here we introduce a new method to monitor the adsorption in situ, based on the different emission behavior of aggregation induced emission (AIE) luminogen in different micro environments. Poly(vinyl alcohol) (PVA) and colloidal silica (CS) were used as a model system. It was found that AIE molecules exhibited extremely low fluorescence intensity in water and PVA solution, while their emission efficiency was enhanced when adsorbed on CS, and became significantly boosted when PVA was adsorbed on CS at the same time. The fluorescence intensity increases with the amount of added PVA and reaches a saturation point, which is earlier than that obtained by the well established solvent relaxation NMR method, due to their different sensitivities for adsorption segments in specific conformation. This new method is advantageous in quick response, where the measurement can be finished within 2 min, while others usually take hours. Therefore, it is expected that this new method may be used to monitor the dynamical adsorption process of polymer on colloidal particles. PMID- 26901267 TI - Influence of Self-Assembled Alkanethiol Monolayers on Stochastic Amperometric On Chip Detection of Silver Nanoparticles. AB - We investigate the influence of self-assembled alkanethiol monolayers at the surface of platinum microelectrode arrays on the stochastic amperometric detection of citrate-stabilized silver nanoparticles in aqueous solutions. The measurements were performed using a microelectrode array featuring 64 individually addressable electrodes that are recorded in parallel with a sampling rate of 10 kHz for each channel. We show that both the functional end group and the total length of the alkanethiol influence the charge transfer. Three different terminal groups, an amino, a hydroxyl, and a carboxyl, were investigated using two different molecule lengths of 6 and 11 carbon atoms. Finally, we show that a monolayer of alkanethiols with a length of 11 carbon atoms and a carboxyl terminal group can efficiently block the charge transfer of free nanoparticles in an aqueous solution. PMID- 26901269 TI - Risk of Delayed Intracerebral Hemorrhage in Anticoagulated Patients after Minor Head Trauma: The Role of Repeat Cranial Computed Tomography. AB - CONTEXT: Patients receiving anticoagulant medications who experience minor head injury are at increased risk of an intracerebral hemorrhage (ICH) developing, even after an initial computed tomography (CT) scan of the brain yields normal findings. Conflicting evidence exists regarding the frequency at which delayed bleeding occurs. OBJECTIVE: To identify the frequency of delayed traumatic ICH in patients receiving warfarin or clopidogrel. DESIGN: We performed a retrospective observational study of adult trauma encounters for anticoagulated patients undergoing head CT at 1 of 13 Kaiser Permanente Southern California Emergency Departments (EDs) between 2007 and 2011. Encounters were identified using structured data from electronic health and administrative records, and then records were individually reviewed for validation of results. MAIN OUTCOME MEASURES: The primary outcome measure was ICH within 60 days of an ED visit with a normal head CT result. RESULTS: Our sample included 443 (260 clopidogrel and 183 warfarin) eligible ED encounters with normal findings of initial head CT. Overall, 11 patients (2.5%, 95% confidence interval [CI] = 1.4%-4.4%) had a delayed ICH, and events occurred at similar rates between the clopidogrel group (6/260, 2.3%, CI 1.1%-5.0%) and warfarin group (5/183, 2.7%, CI 1.2%-6.2%). CONCLUSION: Trauma patients in the ED who are receiving warfarin or clopidogrel have approximately a 2.5% risk of delayed ICH after an initial normal finding on a head CT. PMID- 26901270 TI - Image Diagnosis: Worm-Induced Biliary Obstruction. PMID- 26901268 TI - Weight Loss and the Prevention of Weight Regain: Evaluation of a Treatment Model of Exercise Self-Regulation Generalizing to Controlled Eating. AB - CONTEXT: For decades, behavioral weight-loss treatments have been unsuccessful beyond the short term. Development and testing of innovative, theoretically based methods that depart from current failed practices is a priority for behavioral medicine. OBJECTIVE: To evaluate a new, theory-based protocol in which exercise support methods are employed to facilitate improvements in psychosocial predictors of controlled eating and sustained weight loss. METHODS: Women with obesity were randomized into either a comparison treatment that incorporated a print manual plus telephone follow-ups (n = 55) or an experimental treatment of The Coach Approach exercise-support protocol followed after 2 months by group nutrition sessions focused on generalizing self-regulatory skills from an exercise support to a controlled eating context (n = 55). Repeated-measures analysis of variance contrasted group changes in weight, physical activity, fruit and vegetable intake, mood, and exercise- and eating-related self-regulation and self-efficacy over 24 months. Regression analyses determined salient interrelations of change scores over both the weight-loss phase (baseline-month 6) and weight-loss maintenance phase (month 6-month 24). RESULTS: Improvements in all psychological measures, physical activity, and fruit and vegetable intake were significantly greater in the experimental group where a mean weight loss of 5.7 kg (6.1% of initial body weight) occurred at month 6, and was largely maintained at a loss of 5.1 kg (5.4%) through the full 24 months of the study. After establishing temporal intervals for changes in self-regulation, self efficacy, and mood that best predicted improvements in physical activity and eating, a consolidated multiple mediation model suggested that change in self regulation best predicted weight loss, whereas change in self-efficacy best predicted maintenance of lost weight. CONCLUSIONS: Because for most participants loss of weight remained greater than that required for health benefits, and costs for treatment administration were comparatively low, the experimental protocol was considered successful. After sufficient replication, physician referral and applications within health promotion and wellness settings should be considered. PMID- 26901272 TI - The Jigsaw Puzzle in the Lunchroom. PMID- 26901271 TI - Love and the Value of Life in Health Care: A Narrative Medicine Case Study in Medical Education. AB - This case study is an example of narrative medicine applied to promote self awareness and develop humanistic contents in medical education. The impact and the human appeal of the narrative lie in the maturity and empathy shown by a student when reporting his dramatic experience during the care given to a newborn (with Patau syndrome and multiple malformations diagnosed at birth) and to her mother. The narrative approach helped the student to be successful in bringing out the meaning behind the story and to position himself from the mother's and newborn's perspective. The student's introspection changed a seemingly scary interaction into a positive experience, overcoming many initial negative emotions, such as fear, disappointment, horror, hopelessness, and insecurity in the face of the unexpected. It is uplifting how the student was strengthened by the power of maternal love to the point of overcoming any remaining feelings of eugenics or rejection. Other important lessons emerging from the case study were the art of listening and the value of silence. This narrative shows how the development of narrative competence can help establish a good physician-patient relationship, because the physician or the student with such competence usually confirms the patient's value and demonstrates concern for them, focusing on what they say and allowing genuine contact to be established, which is necessary for effective therapeutic alliance. The student's interpretations of the meaning of love and value of life inspired him on his reframing process of a medical practice marked by vicarious suffering. PMID- 26901273 TI - Long-Term Stable Recombination Layer for Tandem Polymer Solar Cells Using Self Doped Conducting Polymers. AB - Recently, the most efficient tandem polymer solar cells (PSCs) have used poly(3,4 ethylenedioxythiophene):poly(styrenesulfonate) ( PEDOT: PSS) as a p-type component of recombination layer (RL). However, its undesirable acidic nature, originating from insulating PSS, of PEDOT: PSS drastically reduces the lifetime of PSCs. Here, we demonstrate the efficient and stable tandem PSCs by introducing acid-free self-doped conducting polymer (SCP), combined with zinc oxide nanoparticles (ZnO NPs), as RL for PEDOT: PSS-free tandem PSCs. Moreover, we introduce an innovative and versatile nanocomposite system containing photoactive and p-type conjugated polyelectrolyte (p-CPE) into the tandem fabrication of an ideal self-organized recombination layer. In our new RL, highly conductive SCP facilitates charge transport and recombination process, and p-CPE helps to achieve nearly loss-free charge collection by increasing effective work function of indium tin oxide (ITO) and SCP. Because of the synergistic effect of extremely low electrical resistance, ohmic contact, and pH neutrality, tandem devices with our novel RL performed well, exhibiting a high power conversion efficiency of 10.2% and a prolonged lifetime. These findings provide a new insight for strategic design of RLs using SCPs to achieve efficient and stable tandem PSCs and enable us to review and extend the usefulness of SCPs in various electronics research fields. PMID- 26901275 TI - Ultrasound screening for fetal microcephaly following Zika virus exposure. PMID- 26901274 TI - Maternal weight gain in excess of pregnancy guidelines is related to daughters being overweight 40 years later. AB - BACKGROUND: Exceeding the Institute of Medicine guidelines for pregnancy weight gain increases childhood and adolescent obesity. However, it is unknown if these effects extend to midlife. OBJECTIVE: We sought to determine if exceeding the Institute of Medicine guidelines for pregnancy weight gain increases risk of overweight/obesity in daughters 40 years later. STUDY DESIGN: This cohort study is based on adult offspring in the Child Health and Development Studies and the Collaborative Perinatal Project pregnancy cohorts originally enrolled in the 1960s. In 2005 through 2008, 1035 daughters in their 40s were recruited to the Early Determinants of Mammographic Density study. We classified maternal pregnancy weight gain as greater than vs less than or equal to the 2009 clinical guidelines. We used logistic regression to compare the odds ratios of daughters being overweight/obese (body mass index [BMI] >=25) at a mean age of 44 years between mothers who did not gain or gained more than pregnancy weight gain guidelines, accounting for maternal prepregnant BMI, and daughter body size at birth and childhood. We also examined potential family related confounding through a comparison of sisters using generalized estimating equations, clustered on sibling units and adjusted for maternal age and race. RESULTS: Mothers who exceeded guidelines for weight gain in pregnancy were more likely to have daughters who were overweight/obese in their 40s (odds ratio [OR], 3.4; 95% confidence interval {CI}, 2.0-5.7). This magnitude of association translates to a relative risk (RR) increase of 50% (RR = 1.5; 95% CI, 1.3-1.6). The association was of the same magnitude when examining only the siblings whose mother exceeded guidelines in 1 pregnancy and did not exceed the guidelines in the other pregnancy. The association was stronger with increasing maternal prepregnancy BMI (P trend < .001). Compared to mothers with BMI <25 who did not exceed guidelines, the relative risks (RR) for having an overweight/obese adult daughter were 1.3 (95% CI, 1.1-1.7), 1.7 (95% CI, 1.4-2.1) and 1.8 (95% CI, 1.5-2.1), respectively, if mothers exceeded guidelines and their prepregnancy BMI was <25, overweight (BMI 25-<30), or obese (BMI >30). This pattern held irrespective of daughters' weight status at birth, at age 4 years, or at age 20 years. CONCLUSION: Our findings support that obesity prevention before pregnancy and strategies to maintain weight gain during pregnancy within the IOM guidelines might reduce the risk of being overweight in midlife for the offspring. PMID- 26901276 TI - A comparison of 3 antibiotic regimens for prevention of postcesarean endometritis: an historical cohort study. AB - BACKGROUND: Prophylactic antibiotics are of proven value in decreasing the frequency of postcesarean endometritis. The beneficial effect of prophylaxis is enhanced when the antibiotics are administered before the surgical incision as opposed to after the clamping of the umbilical cord. However, the optimal antibiotic regimen for prophylaxis has not been established firmly. OBJECTIVE: The purpose of this study was to compare 3 different antibiotic regimens for the prevention of postcesarean endometritis. STUDY DESIGN: This retrospective historical cohort study was conducted at the University of Florida, which is a tertiary care facility that serves a predominantly indigent patient population. In the period January 2003 to December 2007, our standard prophylactic antibiotic regimen for all women who had cesarean delivery was cefazolin (1 g) administered immediately after the baby's umbilical cord was clamped. In November 2008, we began to administer the combined regimen of cefazolin (1 g intravenously) plus azithromycin (500 mg intravenously); both were given 30-60 minutes before the skin incision. In the period of January-December 2014, we continued the dual agent regimen but based the dose of cefazolin on the patient's body mass index: 2 g intravenously if the body mass index was <30 kg/m(2) and 3 g if the body mass index was >30 kg/m(2). The surgical technique was consistent throughout all 3 time periods. Our primary endpoint was the frequency of endometritis in each time period. This diagnosis was based on fever >=37.5 degrees C, lower abdominal pain and tenderness, the exclusion of other localizing signs of infection, and the requirement for administration of therapeutic antibiotics. In the first year after beginning the new antibiotic regimen, we also monitored the frequency of neonatal sepsis evaluations and compared it with the frequency that was recorded during the year immediately preceding the change in antibiotic regimens. RESULTS: During the entire period 2003-2014, 29,633 women delivered at our institution; 6455 women (22%) had a cesarean delivery. In the period January 2003 to December 2007, 1034 women had a primary or repeat cesarean delivery. One hundred seventy women (16.4%; 95% confidence interval, 14.4-18.4%) developed endometritis. In the period November 2008 to December 2013, 4484 women had a primary or repeat cesarean delivery. Fifty-nine patients (1.3%; 95% confidence interval, 1.0-1.7%) developed endometritis (P < .0001 compared with period 1). In the year 2014, 937 women had a cesarean delivery; 22 of them (2.3%, 95% confidence interval, 1.3 3.3%) developed endometritis (P < .0001 compared with period 1 and P > .5 and <.10 compared with period 2). The frequency of evaluations for suspected neonatal sepsis in infants who were delivered to mothers who had cesarean delivery was 17.6% in the period January to December 2007 and 19.3% in the period November 2008 to November 2009 (relative risk, 1.1; 95% confidence interval, 0.7-1.9). One infant had proven sepsis in the former period; 2 infants had proven sepsis in the latter period (not significant). CONCLUSIONS: When administered before skin incision, the combination of cefazolin plus azithromycin was significantly more effective in the prevention of endometritis than the administration of cefazolin after cord clamping; the rate of endometritis was reduced to a very low level without increasing the rate of neonatal sepsis evaluations. PMID- 26901277 TI - The gut microbiota: a puppet master in the pathogenesis of endometriosis? AB - Endometriosis is a frequent gynecologic disease with a complex, multifactorial cause. It is characterized by the cyclic estrogen-driven proliferation and bleeding of endometriotic lesions (ie, ectopic endometrial glands and stroma) outside the uterus. These lesions induce a chronic activation of the innate immune system within the peritoneal cavity that is associated with the release of various inflammatory cytokines and angiogenic growth factors into the peritoneal fluid. This stimulates angiogenesis and the further spread of the lesions and triggers the typical pain that is symptomatic of the disease. Moreover, circulating stem and progenitor cells are recruited into the ectopic endometrial tissue and contribute to its growth and vascularization. In recent years, an increasing number of studies have indicated that the gut microbiota is not only essential for a physiologic gastrointestinal function but acts as a central regulator of a variety of inflammatory and proliferative conditions. Besides, the gut flora affects estrogen metabolism and stem-cell homeostasis. Based on these findings, we hypothesize that the gut microbiota may be involved crucially in the onset and progression of endometriosis. In the future, this novel view of the pathogenesis of endometriosis may be verified by analysis of the development of endometriotic lesions in animal models with a defined composition of the gut microbiota and by investigation of the microbiota of patients with endometriosis with modern next-generation sequencing tools. This could open the door for completely new preventive, diagnostic, and therapeutic approaches for endometriosis. PMID- 26901279 TI - A Common Clinical Dilemma: Management of Abnormal Vaginal Cytology and Human Papillomavirus Test Results. AB - OBJECTIVE: Vaginal cancer is an uncommon cancer of the lower genital tract, and standardized screening is not recommended. Risk factors for vaginal cancer include a history of other lower genital tract neoplasia or cancer, smoking, immunosuppression, and exposure to diethylstilbestrol in utero. Although cervical cancer screening after total hysterectomy for benign disease is not recommended, many women inappropriately undergo vaginal cytology and/or human papillomavirus (HPV) tests, and clinicians are faced with managing their abnormal results. Our objectives were to review the literature on vaginal cytology and high-risk HPV (hrHPV) testing and to develop guidance for the management of abnormal vaginal screening tests. MATERIALS AND METHODS: An electronic search of the PubMed database through 2015 was performed. Articles describing vaginal cytology or vaginal hrHPV testing were reviewed, and diagnostic accuracy of these tests when available was noted. RESULTS: The available literature was too limited to develop evidence-based recommendations for managing abnormal vaginal cytology and hrHPV screening tests. However, the data did show that (1) the risk of vaginal cancer in women after hysterectomy is extremely low, justifying the recommendation against routine screening, and (2) in women for whom surveillance is recommended, e.g., women posttreatment for cervical precancer or cancer, hrHPV testing may be useful in identification of vaginal cancer precursors. CONCLUSIONS: Vaginal cancer is rare, and asymptomatic low-risk women should not be screened. An algorithm based on expert opinion is proposed for managing women with abnormal vaginal test results. PMID- 26901278 TI - Hyperglycemia-Induced Hypovolemia Is Involved in Early Cardiac Magnetic Resonance Alterations in Streptozotocin-Induced Diabetic Mice: A Comparison with Furosemide Induced Hypovolemia. AB - AIMS: The aim of the study was to assess the early features of diabetic cardiomyopathy using cardiac magnetic resonance within the first week after streptozotocin injection in mice. We focused on the relationship between left ventricular function and hypovolemia markers in diabetic animals compared to a hypovolemic rodent model. METHODS AND RESULTS: Swiss mice were randomized into control (group C), streptozotocin-induced diabetes (group D) and furosemide induced hypovolemia (group F) groups. Cardiac magnetic resonance, non-invasive blood pressure, urine volume, plasma markers of dehydration and cardiac histology were assessed in all groups. Mean blood glucose was higher in diabetic animals than in groups C and F (30.5+/-5.8 compared to 10.4+/-2.1 and 11.1+/-2.8 mmol/L, respectively; p<0.01). Diuresis was increased in animals from group D and F compared to C (14650+/-11499 and 1533+/-540 compared to 192+/-111 MUL/24 h; p<0.05). End diastolic and end systolic volumes were lower in group D than in group C at week 1 (1.52+/-0.36 vs. 1.93+/-0.35 and 0.54+/-0.22 vs. 0.75+/-0.18 mL/kg, p<0.05). These left ventricular volume values in group D were comparable to those observed in the acute hypovolemia model (group F). Increased dehydration plasma markers and an absence of obvious intrinsic myocardial damage (evaluated by cardiac magnetic resonance and histology) suggest that a hemodynamic mechanism underlies the very early drop in left ventricular volumes in group D and provides a potential link to hyperglycemic osmotic diuresis. CONCLUSIONS: Researchers using cardiac magnetic resonance in hyperglycemic rodent models should be aware of this hemodynamic mechanism, which may partially explain modifications in cardiac parameters in addition to diabetic myocardial damage. PMID- 26901280 TI - Screening for Spiritual Struggle in an Adolescent Transgender Clinic: Feasibility and Acceptability. AB - Spiritual struggles are associated with poorer health outcomes, including depression, which has higher prevalence among transgender individuals than the general population. This study's objective was to improve the quality of care in an outpatient transgender clinic by screening patients and caregivers for spiritual struggle and future intervention. The quality improvement questions addressed were whether screening for spiritual struggle was feasible and acceptable; and whether the sensitivity and specificity of the Rush Protocol were acceptable. Revision of the screening was based on cognitive interviews with the 115 adolescents and caregivers who were screened. Prevalence of spiritual struggle was 38-47%. Compared to the Negative R-COPE, the Rush Protocol screener had sensitivities of 44-80% and specificities of 60-74%. The Rush Protocol was acceptable to adolescents seen in a transgender clinic, caregivers, and clinic staff; was feasible to deliver during outpatient clinic visits, and offers a straightforward means of identifying transgender persons and caregivers experiencing spiritual struggle. PMID- 26901281 TI - Health Care Chaplaincy: A Scoping Review of the Evidence 2009-2014. AB - There is a growing body of evidence investigating chaplaincy services. The purpose of this scoping review was to examine the empirical literature specific to the role of chaplaincy within health care published since 2009. Electronic searches of four databases were conducted in August 2015. After screening, 48 studies were retained and reviewed. Four themes emerged: experiences and perceptions of the health care chaplain (n = 15), chaplain practice (n = 9), emerging areas of health care chaplaincy (n = 16), and outcome studies (n = 8). Studies were diverse in topics covered, methods, national contexts, and clinical settings. The majority were descriptive in nature. Evidence continues to demonstrate a relationship between chaplains and increased patient satisfaction. Nascent areas of research include chaplain's role with diverse populations, involvement in clinical ethics, and confidence with research and evidence-based practice. Few conclusions can be drawn from the limited evidence on the outcomes of chaplain interventions. PMID- 26901282 TI - Direct Measurement of the Thermodynamics of Chiral Recognition in Bile Salt Micelles. AB - Isothermal titration calorimetry (ITC) is shown to be a sensitive reporter of bile salt micellization and chiral recognition. Detailed ITC characterization of bile micelle formation as well as the chiral recognition capabilities of sodium cholate (NaC), deoxycholate (NaDC), and taurodeoxycholate (NaTDC) micelle systems are reported. The DeltaH(demic) of these bile salt micelle systems is directly observable and is strongly temperature-dependent, allowing also for the determination of DeltaCp(demic). Using the pseudo-phase separation model, DeltaG(demic) and TDeltaS(demic) were also calculated. Chirally selective guest host binding of model racemic compounds 1,1'-bi-2-napthol (BN) and 1,1' binaphthyl-2,2'-diylhydrogenphosphate (BNDHP) to bile salt micelles was then investigated. The S-isomer was shown to bind more tightly to the bile salt micelles in all cases. A model was developed that allows for the quantitative determination of the enthalpic difference in binding affinity that corresponds to chiral selectivity, which is on the order of 1 kJ mol(-1). PMID- 26901283 TI - Role of Particle Focusing in Resistive-Pulse Technique: Direction-Dependent Velocity in Micropores. AB - Passage time through single micropores is an important parameter used to quantify the surface charge and zeta potential of particles. In the resistive-pulse technique, the measured time of pressure- or electric-field-induced translocation is assumed to be direction independent. This assumption is supported by the low velocities of the particles and the supporting fluid such that the transport reversibility known for Stokes flow is expected to apply. In this article, we present examples of micropores in which passage time of ~400 nm diameter particles becomes direction-dependent; that is, the particles' translocation times from left to right and right to left are different. These pores are characterized by an undulating inner diameter such that at least one wider zone called a cavity separates two narrower regions of different lengths. We propose that the observed direction-dependence of the translocation velocity is caused by an asymmetric efficiency of particle focusing toward the pore axis, which leads to a direction-dependent set of particle trajectories. The reported pores present the simplest system in which time-broken symmetry has been observed. The results are of importance for sensing of particles and molecules by the resistive-pulse technique since pores used for detection are often characterized by finite roughness or noncylindrical shape. This article also points to the role of particle focusing in the magnitude and distribution of the translocation times. PMID- 26901284 TI - Next-Generation Sequencing Informatics: Challenges and Strategies for Implementation in a Clinical Environment. AB - CONTEXT: -Next-generation sequencing (NGS) is revolutionizing the discipline of laboratory medicine, with a deep and direct impact on patient care. Although it empowers clinical laboratories with unprecedented genomic sequencing capability, NGS has brought along obvious and obtrusive informatics challenges. Bioinformatics and clinical informatics are separate disciplines with typically a small degree of overlap, but they have been brought together by the enthusiastic adoption of NGS in clinical laboratories. The result has been a collaborative environment for the development of novel informatics solutions. Sustaining NGS based testing in a regulated clinical environment requires institutional support to build and maintain a practical, robust, scalable, secure, and cost-effective informatics infrastructure. OBJECTIVE: -To discuss the novel NGS informatics challenges facing pathology laboratories today and offer solutions and future developments to address these obstacles. DATA SOURCES: -The published literature pertaining to NGS informatics was reviewed. The coauthors, experts in the fields of molecular pathology, precision medicine, and pathology informatics, also contributed their experiences. CONCLUSIONS: -The boundary between bioinformatics and clinical informatics has significantly blurred with the introduction of NGS into clinical molecular laboratories. Next-generation sequencing technology and the data derived from these tests, if managed well in the clinical laboratory, will redefine the practice of medicine. In order to sustain this progress, adoption of smart computing technology will be essential. Computational pathologists will be expected to play a major role in rendering diagnostic and theranostic services by leveraging "Big Data" and modern computing tools. PMID- 26901285 TI - Favorable outcome of alternate systemic and intra-arterial chemotherapy for retinoblastoma. AB - The recent trend of treatment for retinoblastoma is to salvage the eye globes as well as achieving patients' survival. Intra-arterial chemotherapy (IAC) is one of the current standard treatment; however, it cannot exclude the risk of occult micrometastases in the central nervous system in advanced-stage retinoblastoma. Alternate fashion of intravenous chemotherapy (IVC) and IAC strategy was developed to increase the eye salvage rate and to reduce the metastatic risk. Between January 2012 and December 2014, 13 eyes of 12 patients with newly diagnosed retinoblastoma received alternate chemotherapy using IVC and IAC in Yonsei Cancer Center. Eye salvage rate was assessed by the eye preservation time, which was defined as the duration from the diagnosis to the time of enucleation. Total 13 eyes were classified according to the International Classification of Retinoblastoma (ICRB) as group B (n = 1, 7.7%), group C (n = 2, 15.4%), group D (n = 5, 38.5%), or group E (n = 5, 38.5%). IAC was performed, 3 to 5 times (median: 4 times) for each eye, total 54 times. Five to 15 courses (median: 8 courses) of systemic chemotherapy were performed in the patients. During the median follow-up period of 30.4 months, overall eye salvage rate was 63.9 +/- 14.7%. All patients survived. The treatment was tolerable without significant complications. These results showed that primary alternate IVC-IAC was tolerable and effective for retinoblastoma. PMID- 26901286 TI - Correction: Bioconversion of Pinoresinol Diglucoside and Pinoresinol from Substrates in the Phenylpropanoid Pathway by Resting Cells of Phomopsis sp.XP-8. PMID- 26901288 TI - Obstructive sleep apnea in preschool-aged Japanese children - efficiency of screening using lateral neck radiography. AB - Conclusions The prevalence of obstructive sleep apnea (OSA) in preschool-aged children diagnosed by the International Classification of Sleep Disorders (ICSD) version 3 criteria was relatively higher than that diagnosed by ICSD-2. Although the assessment of the upper airway by lateral neck radiography was effective for detecting OSA in this age group, this assessment is not recommended for all children as a screening method because of parental concern related to radiation exposure. Objective This study investigated the prevalence of OSA and the screening capacity of lateral neck radiography in community-based preschool-aged children. Methods Parents of 211 children aged 3-6 years were requested to complete the sleep-related questionnaire. Subjects who agreed to further investigations were invited to undergo home type 3 portable monitoring and clinical examination, including radiography. We estimated the prevalence of OSA and evaluated the detection power of radiography for predicting OSA. Results One hundred and eighty-eight (89.1%) subjects completed the questionnaire and 67 (31.8%) agreed to further examinations. The weighted prevalence was 7.3% and 12.8% by ICSD-2 and 3, respectively. Area under the receiver operator curve for the adenoidal/nasopharyngeal and tonsil/pharyngeal ratios measured using radiography was slightly larger than that for tonsil size graded by visual inspection. PMID- 26901287 TI - Multifunctional nanoparticles for cancer immunotherapy. AB - During the last decades significant progress has been made in the field of cancer immunotherapy. However, cancer vaccines have not been successful in clinical trials due to poor immunogenicity of antigen, limitations of safety associated with traditional systemic delivery as well as the complex regulation of the immune system in tumor microenvironment. In recent years, nanotechnology-based delivery systems have attracted great interest in the field of immunotherapy since they provide new opportunities to fight the cancer. In particular, for delivery of cancer vaccines, multifunctional nanoparticles present many advantages such as targeted delivery to immune cells, co-delivery of therapeutic agents, reduced adverse outcomes, blocked immune checkpoint molecules, and amplify immune activation via the use of stimuli-responsive or immunostimulatory materials. In this review article, we highlight recent progress and future promise of multifunctional nanoparticles that have been applied to enhance the efficiency of cancer vaccines. PMID- 26901289 TI - Comorbid substance use diagnoses and partner violence among offenders receiving pharmacotherapy for opioid dependence. AB - While previous studies find mixed evidence of an association between opioid use and intimate partner violence perpetration among community samples, initial evidence has detected increased rates of partner violence among individuals receiving pharmacological intervention for opioid dependence. The current study evaluated the role of current comorbid substance use diagnoses, a robust risk factor for violent behavior, on the likelihood of perpetrating partner violence among a high risk sample of offenders receiving pharmacological intervention for opioid dependence. The authors analyzed self-report data provided by 81 (55 male) opioid dependent offenders during a court-ordered substance use interview. Approximately one-third of the sample evidenced the recent use of intimate partner violence. Findings indicated that cocaine and benzodiazepine use were independently associated with an increased likelihood of reporting physical partner violence. Alcohol and cannabis use were not associated with partner violence. The current results offer further support for the ongoing need to conduct routine partner violence screenings among substance involved offenders and highlight the importance of developing individualized treatment plans that address comorbid substance use and partner-violent behaviors among individuals in treatment for opioid dependence. PMID- 26901292 TI - On the Use of Dynamical Diffraction Theory To Refine Crystal Structure from Electron Diffraction Data: Application to KLa5O5(VO4)2, a Material with Promising Luminescent Properties. AB - A new lanthanum oxide, KLa5O5(VO4)2, was synthesized using a flux growth technique that involved solid-state reaction under an air atmosphere at 900 degrees C. The crystal structure was solved and refined using an innovative approach recently established and based on three-dimensional (3D) electron diffraction data, using precession of the electron beam and then validated against Rietveld refinement and denisty functional theory (DFT) calculations. It crystallizes in a monoclinic unit cell with space group C2/m and has unit cell parameters of a = 20.2282(14) A, b = 5.8639(4) A, c = 12.6060(9) A, and beta = 117.64(1) degrees . Its structure is built on Cresnel-like two-dimensional (2D) units (La5O5) of 4*3 (OLa4) tetrahedra, which run parallel to (001) plane, being surrounded by isolated VO4 tetrahedra. Four isolated vanadate groups create channels that host K(+) ions. Substitution of K(+) cations by another alkali metal is possible, going from lithium to rubidium. Li substitution led to a similar phase with a primitive monoclinic unit cell. A complementary selected area electron diffraction (SAED) study highlighted diffuse streaks associated with stacking faults observed on high-resolution electron microscopy (HREM) images of the lithium compound. Finally, preliminary catalytic tests for ethanol oxidation are reported, as well as luminescence evidence. This paper also describes how solid-state chemists can take advantages of recent progresses in electron crystallography, assisted by DFT calculations and powder X-ray diffraction (PXRD) refinements, to propose new structural types with potential applications to the physicist community. PMID- 26901290 TI - Adder and a coarse-grained approach to cell size homeostasis in bacteria. AB - Cell size control and homeostasis is a long-standing subject in biology. Recent experimental work provides extensive evidence for a simple, quantitative size homeostasis principle coined adder (as opposed to sizer or timer). The adder principle provides unexpected insights into how bacteria maintain their size without employing a feedback mechanism. We review the genesis of adder and recent cell size homeostasis study on evolutionarily divergent bacterial organisms and beyond. We propose new coarse-grained approaches to understand the underlying mechanisms of cell size control at the whole cell level. PMID- 26901293 TI - Vertical Bone Grafting and Periosteal Vertical Mattress Suture for the Fixation of Resorbable Membranes and Stabilization of Particulate Grafts in Horizontal Guided Bone Regeneration to Achieve More Predictable Results: A Technical Report. AB - Osteosynthesis screws and titanium or resorbable pins have been recommended for fixing guided bone regeneration (GBR) membranes and stabilizing the graft. However, the removal of fixation screws or pins often requires an additional surgical procedure. This article presents a periosteal suturing technique with resorbable sutures for the fixation of grafts and membranes in GBR in single implant sites. This technique avoids potential complications of using fixation screws or pins, such as perforation of the roots when inserting the pins, and eliminates the need for a second retrieval surgery. PMID- 26901291 TI - Jujuboside B Reduces Vascular Tension by Increasing Ca2+ Influx and Activating Endothelial Nitric Oxide Synthase. AB - Jujuboside B has been reported to have protective effect on many cardiovascular diseases. However, the effects of Jujuboside B on vascular tension and endothelial function are unknown. The present study investigated the effects of Jujuboside B on reducing vascular tension, protecting endothelial function and the potential mechanisms. The tension of isolated rat thoracic aorta ring was measured by Wire myograph system. The concentration of nitric oxide (NO) and the activity of endothelial nitric oxide synthase (eNOS) in human aortic endothelial cells (HAECs) were determined by Griess reagent method and enzyme-linked immune sorbent assay. The protein levels of eNOS and p-eNOS at Serine-1177 were determined by western blot analysis. Intracellular Ca2+ concentration in HAECs was measured by laser confocal imaging microscopy. Results showed that Jujuboside B reduced the tension of rat thoracic aorta rings with intact endothelium in a dose-dependent manner. L-NAME, KN93, EGTA, SKF96365, iberiotoxin and glibenclamide significantly attenuated Jujuboside B-induced vasodilation in endothelium-intact tissues. In contrast, indometacin and 4-DAMP had no such effects. Jujuboside B also promoted NO generation and increased eNOS activity, which were attenuated by L-NAME, EGTA and SKF96365. Moreover, Jujuboside B increased intracellular Ca2+ concentration dose-dependently, which was inhibited by EGTA and SKF96365. Besides, Jujuboside B induced a rapid Ca2+ influx instantaneously after depleting intracellular Ca2+ store, which was significantly inhibited by SKF96365. In conclusion, this study preliminarily confirmed that Jujuboside B reduced vascular tension endothelium-dependently. The underlying mechanisms involved that Jujuboside B increased extracellular Ca2+ influx through endothelial transient receptor potential cation (TRPC) channels, phosphorylated eNOS and promoted NO generation in vascular endothelial cells. In addition, Jujuboside B-induced vasodilation involved endothelium-dependent hyperpolarizaiton through endothelial potassium channels. Jujuboside B is a natural compound with new pharmacological effects on improving endothelial dysfunction and treating vascular diseases. PMID- 26901294 TI - New Surgical Protocol to Create Interimplant Papilla: The Preliminary Results of a Case Series. AB - The aim of this study was to introduce a new surgical technique to regenerate the papilla adjacent to multiple or single implants using a novel instrument and a new incision design. A total of 10 consecutively treated patients with maxillary anterior implant-supported provisional restorations and missing interproximal papillae received a subepithelial connective tissue graft. The recipient site was prepared with a buccal incision apical to the mucogingival junction and to the defective papilla, and a palatal incision, followed by buccolingual tunneling performed with a translingual curette (EBINA). A total of 10 sites were treated and evaluated pre- and postoperatively with the papilla score based on the Jemt classification. The final prosthesis was delivered 3 months after the papilla regeneration surgical procedure. An average improvement in papilla index score from 0.8 to 2.4 was found after an average follow-up period of 16.3 months. This case series demonstrated that interimplant papilla regeneration can be successful over a period of 11 to 30 months postloading. Long-term prospective studies on tissue stability and esthetic outcomes are needed to corroborate the findings in this study. PMID- 26901295 TI - Treatment of Moderate to Severe Buccal Gingival Recession Defects with Placental Allografts. AB - A multicenter prospective consecutive case series study was conducted to evaluate the effectiveness of placental allografts to correct moderate to severe buccogingival recession defects. Nineteen healthy patients, 13 women and 6 men, ranging in age from 29 to 63 years, with 43 maxillary and mandibular gingival recession defects of > 4 mm deep were included. Clinical examination at multiple postsurgery time points revealed healthy maturation of gingival tissues with normal color and texture matched to adjacent soft tissue areas. Complete root coverage was not achieved in all cases in this proof of principle evaluation. Severe buccal bone loss had occurred in most of the selected cases, which may have negatively influenced the results. Nonetheless, it was possible to achieve root coverage and demonstrate gain in clinical attachment level and height of keratinized tissue when placental allograft was used. Future randomized clinical trials are needed to further explore the potential of placental allografts for treatment of localized gingival recession defects. PMID- 26901296 TI - Horizontal Ridge Augmentation with a Novel Resorbable Collagen Membrane: A Retrospective Analysis of 36 Consecutive Patients. AB - The aim of this investigation was to evaluate a new resorbable, monolayer, noncross-linked collagen barrier membrane for immobilizing bone augmentation material during horizontal guided bone regeneration (GBR) procedures. GBR was performed on 36 consecutive patients in 49 sites, with 103 implants placed either simultaneously or after a healing period. Healing time, suture retention, postoperative complications, and functional outcome after GBR, implant placement, and prosthesis loading were assessed. A wound dehiscence rate of only 12% and a graft failure rate of 4% occurred. Mean healing time was 5.8 months for simultaneous placement and 7.9 + 4.8 months for two-stage procedures. The implant survival rate was 100% after a mean follow-up of 18.3 months from implantation. These early data demonstrate a low dehiscence rate and excellent potential of this new noncross-linked collagen membrane for use with horizontal ridge augmentation. PMID- 26901297 TI - Three Years of a Nonsurgical Periodontal Treatment Protocol to Observe Clinical Outcomes in >= 6-mm Pockets: A Retrospective Case Series. AB - A total of 25 patients were treated with a nonsurgical periodontal treatment protocol (NSPTP) consisting of four appointments (three within 1 week and one approximately 30 days later). Nonsurgical periodontal instrumentation was implemented, with the adjunctive use of thermal diode lasers (wavelength of 808 or 980 nm). The patients were scheduled for recall visits every 3 months and reevaluated 1 year post-NSPTP. They were subsequently monitored at 4-month intervals for the remaining 2-year follow-up maintenance period. In total, 698 teeth (210 multirooted and 488 single-rooted) were included in the study. The mean bleeding on probing was 43% at baseline and decreased to 12% at 12 months and to 8% at 3 years. The initial >= 6-mm probing pocket depth (PPD) in single rooted teeth decreased from 6.2 mm at baseline to a mean of 1.8 mm at 12 months and remained at 1.8 mm at 3 years, with a mean clinical attachment level (CAL) gain of 4.4 mm. In multirooted teeth, the PPD decreased from 6.7 mm to a mean of 3.9 mm at 12 months and 3.6 mm at 3 years, with a mean CAL gain of 2.9 mm. The mean overall recession was 0.3 mm at baseline, 0.1 mm at 1 year, and 0.3 mm at the 3-year follow-up. In the short-term followup period, uniform and consistent implementation of the NSPTP used here with adjunctive use of thermal diode lasers seemed to convey therapeutic benefits, stable periodontal soft tissue levels, and satisfactory esthetics in patients with moderate to severe chronic periodontitis. The present protocol is relevant as a treatment option for medically compromised patients, those who refuse or delay surgical treatment, or those who present with other limitations. PMID- 26901298 TI - Mini-invasive Implant Placement in Combination with Maxillary Sinus Membrane Perforation During Transcrestal Sinus Floor Elevation: A Retrospective Study. AB - The aim of this retrospective study was to report preliminary outcomes of a modified technique for transcrestal sinus floor elevation with simultaneous implant placement. A total of 165 implants were placed in 110 patients using a modified Summers technique. During implant site preparation, after fracturing the sinus floor, a small perforation of the membrane was made using the first osteotome. After grafting with anorganic bovine bone mixed with venous blood, standard-length implants were inserted. The prosthetic phase occurred after 4 to 5 months. Patients were followed for at least 2 years after loading. During the follow-up, sinus condition was assessed by cone beam computed tomography. Periapical radiographs were taken to assess graft height and peri-implant bone levels. Three implants failed within 2 months of placement, yielding an overall implant survival of 98.2%. The mean follow-up was 38.3 months (range: 28 to 60 months) from placement. All other implants were stable and peri-implant soft tissues were healthy throughout the observation period. Peri-implant bone loss averaged 0.62 +/- 0.26 mm after 1 year of function. No biologic or biomechanical complications occurred. No evidence of graft material dispersion into the sinus space was detected, except for two cases that resolved spontaneously. After 1 year of loading the graft height averaged 4.8 +/- 1.3 mm above the sinus floor level. In the presence of sinus membrane perforation, the proposed modified osteotome technique may allow a predictable rehabilitation of the atrophic posterior maxilla by means of standard length implants without the occurrence of adverse events. PMID- 26901299 TI - A Clinical and Radiographic Assessment of Positional Variations of Gingival Papilla and Its Proportions. AB - In 60 healthy subjects, 720 interdental papilla sites in maxillary anterior teeth were investigated. Interdental papilla heights were measured from the gingival zenith along the clinical crown lengths. Radiovisiography was used to measure the relative bone length. Percentage of papilla height to crown length and radiographic bone length to crown length were computed and defined as papilla proportion (PP) and crestal papilla proportion (cPP), respectively. The overall mean mesial PP was 44.95 +/- 6.80% and distal PP was 45.70 +/- 7.87%. The total mean mesial cPP was 54.12 +/- 9.50% and distal cPP was 54.95 +/- 9.28%. Taken together, the cPP was around 55% and the PP was around 45% for all tooth groups. PMID- 26901300 TI - Soft Tissue and Marginal Bone Adaptation on Platform-Switched Implants with a Morse Cone Connection: A Histomorphometric Study in Dogs. AB - The purpose of this study was to investigate peri-implant tissue adaptation on platform-switched implants with a Morse cone-type connection, after 3 and 12 weeks of healing in dogs. Ten weeks after mandibular premolar extractions, eight beagle dogs received three implants each. At each biopsy interval, four animals were sacrificed and biopsies were processed for histologic analysis. The height of the peri-implant mucosa was 2.32 mm and 2.88 mm, respectively, whereas the bone level in relation to the implant platform was -0.39 mm and -0.67 mm, respectively, after 3 and 12 weeks of healing. Within the limits of the present study, platform-switched implants exhibited reduced values of biologic width and marginal bone loss when compared with previous data. PMID- 26901301 TI - Multiple Gingival Recession Defects Treated with Coronally Advanced Flap and Either the VISTA Technique Enhanced with GEM 21S or Periosteal Pedicle Graft: A 9 Month Clinical Study. AB - The objective of this study was to clinically evaluate and compare the efficacy of the vestibular incision subperiosteal tunnel access (VISTA) technique using Bio-Gide (Geistlich) membrane enhanced with GEM 21S (Osteohealth) with periosteal pedicle graft (PPG) using a coronally advanced flap. Multiple gingival recession sites in 15 individuals were randomly assigned either to experimental site A (VISTA) or experimental site B (PPG) in a split-mouth design. The clinical parameters were recorded at baseline and 9 months postoperatively. Repeated measures analysis of variance with post hoc Bonferroni correction and paired t test were used to assess statistical significance (P < .05). Mean recession depth significantly decreased from 4.21 +/- 1.08 mm (presurgery) to 0.61 +/- 0.92 mm (9 months) with VISTA (87.37 +/- 17.78% root coverage) and from 4.17 +/- 1.18 mm (presurgery) to 1.16 +/- 0.92 mm (9 months) with PPG (71.84 +/- 19.25% root coverage). Width of keratinized tissue and clinical attachment gain were significantly higher in the VISTA group compared with the PPG group. Within the limits of the study both VISTA and PPG groups resulted in a significant amount of root coverage. The VISTA technique was less invasive and required minimal time and clinical maneuvering. It also resulted in a superior esthetic outcome. PMID- 26901302 TI - Optimizing Esthetics and Function in a Case of Moderate Reduced Bone Support. AB - The aim of this article is to report the orthodontic treatment of a woman aged 53 years 6 months whose chief complaint involved her facial esthetics and crowding. She presented a moderate reduction in bone support, but no periodontal disease, over the past 15 years. The maxillary left first premolar and both mandibular first premolars were extracted. The dental protrusion was reduced and all the spaces were closed, resulting in a significant improvement in facial esthetics. After 16 months, the satisfactory results in terms of the functional position of the teeth were maintained with the bone level remaining unchanged. PMID- 26901303 TI - Clinical Comparison of At-Home and In-Office Dental Bleaching Procedures: A Randomized Trial of a Split-Mouth Design. AB - The objective of this split-mouth clinical study was to compare a combination of in-office and at-home dental bleaching with at-home bleaching alone. Two applications of in-office bleaching were performed, with one appointment per week, using 38% hydrogen peroxide. At-home bleaching was performed with or without in-office bleaching using 10% carbamide peroxide in a custom-made tray every night for 2 weeks. The factor studied was the bleaching technique on two levels: Technique 1 (in-office bleaching combined with home bleaching) and Technique 2 (home bleaching only). The response variables were color change, dental sensitivity, morphology, and surface roughness. The maxillary right and left hemiarches of the participants were submitted to in-office placebo treatment and in-office bleaching, respectively (Phase 1), and at-home bleaching (Phase 2) treatment was performed on both hemiarches, characterizing a split-mouth design. Enamel surface changes and roughness were analyzed with scanning electron microscopy and optical interferometry using epoxy replicas. No statistically significant differences were observed between the bleaching techniques for either the visual or the digital analyses. There was a significant difference in dental sensitivity when both dental bleaching techniques were used, with in-office bleaching producing the highest levels of dental sensitivity after the baseline. Microscopic analysis of the morphology and roughness of the enamel surface showed no significant changes between the bleaching techniques. The two techniques produced similar results in color change, and the combination technique produced the highest levels of sensitivity. Neither technique promoted changes in morphology or surface roughness of enamel. PMID- 26901304 TI - Periodontal Management of a Patient Undergoing Liver Transplantation. AB - This case report describes the periodontal management of a patient with end-stage liver disease undergoing liver transplantation. In the first part of this article, all medical and dental findings are reported to elaborate adequate diagnoses. A patient-specific treatment plan was structured given the challenging periodontal and systemic scenarios. The second part describes the periodontal therapy delivered in close interaction with the referring physicians. Last, the article reviews current principles and protocols in managing these patients. PMID- 26901305 TI - Effects of Repeated Screw Tightening on Implant Abutment Interfaces in Terms of Bacterial and Yeast Leakage in Vitro: One-Time Abutment Versus the Multiscrewing Technique. AB - Screw loosening can damage the interfaces of implant components, resulting in susceptibility to contamination of the internal parts by microorganisms. The aim of this study was to investigate the impact of abutment screw retightening on the leakage of two different types of bacteria, Streptococcus sanguinis and Fusobacterium nucleatum, and of the yeast Candida albicans. Two types of implant abutment systems with tube-in-tube interfaces were tested. Groups A and B each used a different type of system that consisted of 20 different pieces that were assembled according to the manufacturer's torque recommendations; four samples in each group were closed just one time, four samples three times, four samples five times, four samples seven times, and four samples nine times. The implants of groups A and B were contaminated with 0.1 MUL of microbial solution just before being assembled for the last time to minimize the possibility of contamination. Results showed a direct correlation between the number of colony-forming units grown in the plates and the closing/opening cycles of the implant-abutment systems. Within the limitations of this study, the results indicate the possibility that repeated closing/opening cycles of the implant-abutment unit may influence bacterial/yeast leakage, most likely as a consequence of decreased precision of the coupling between the abutment and the internal part of the dental implant. These findings suggest that a one-time abutment technique may avoid microbiologic leakage in cases of implant-abutment systems with tube-in tube interfaces. PMID- 26901306 TI - Socket Preservation Therapy with Acellular Dermal Matrix and Mineralized Bone Allograft After Tooth Extraction in Humans: A Clinical and Histomorphometric Study. AB - The aim of this study was to analyze through clinical and histomorphometric parameters the use of acellular dermal matrix (ADM) with or without mineralized bone allograft (AB) on bone formation in human alveoli after a 6- to 8-month healing period. A total of 19 patients in need of extraction of the maxillary anterior teeth were selected and randomly assigned to the test group (ADM plus AB) or to the control group (ADM only). Clinical and histomorphometric measurements and histologic analysis were recorded 6 to 8 months after ridge preservation procedures. Clinical parameters and amount of mineralized and nonmineralized tissue were measured and analyzed. In the clinical measurements, the test group showed reduced bone loss in the buccopalatal dimension after 6 to 8 months (intragroup analysis P < .01). Histologic findings showed higher percentages of mineralized tissue and lower percentages of nonmineralized tissue in the test group when compared with the control group (P < .05). In this randomized controlled clinical and histomorphometric study in humans, acellular dermal matrix in association with mineralized bone allograft reduced alveolar bone loss in the anterior maxillae both in height and width after a follow-up period of 6 to 8 months. PMID- 26901307 TI - Flapless Extraction Socket Healing Around an Immediate Implant Placed into a Mandibular Molar Site Without the Use of Regenerative Materials: A Case Report. AB - The aim of this case report is to expand on previous studies of flapless immediate implant placement in sites with a large gap distance, without the application of regenerative materials. In this case report, an immediate implant was placed in a fresh molar extraction site with a large gap distance from the implant surface to the socket walls without the use of a bone graft, membrane, or coronal flap advancement for primary closure. Clinical healing was consistent with spontaneous extraction socket healing. Uncovery at 3 months revealed complete socket fill and secondary stability of the implant. After 2 years and 2 months, bone levels remain stable. This case report demonstrates the natural healing potential of an extraction socket, which can provide sufficient bone healing and dimensional stability for implant osseointegration and a functional restoration. PMID- 26901308 TI - A Case Report of Esthetic and Functional Correction of Maxillary Protrusion Using a Prosthodontics-Centered Multidisciplinary Approach. AB - Maxillary protrusion usually requires orthodontic therapy and orthognathic surgery. However, for some exceptional cases, a prosthodontics-centered multidisciplinary approach could serve as an alternative. This case report describes a 53-year-old patient with protrusive and proclined maxillary incisors, compensatory eruption of mandibular incisors, color and morphologic abnormalities of anterior teeth lip incompetence, and gummy smile. Final esthetic improvement was achieved in this patient by means of a multidisciplinary approach involving endodontic and periodontal procedures before prosthodontic treatment. Accurate diagnosis, comprehensive communication, a sophisticated treatment plan, and state of-the-art therapeutic processes are all important factors for achieving a predictable esthetic result. PMID- 26901309 TI - A Morphometric Study of Labial Grooves on Anterior Maxillary Dentition. AB - This study was performed to investigate the shape, characteristics, and correlation of labial grooves on anterior maxillary dentition. Individual teeth (N = 621) were investigated using a microscopic three-dimensional digital image correlation system. The average length, width, and depth of grooves were quantified, and groove patterns in anterior maxillary teeth and the symmetry and correlation of grooves in anterior maxillary dentition were studied. There were nine common groove patterns in central incisors, eight in lateral incisors, and nine in canines. A good symmetry of grooves was found between the left and right dentition. The number of grooves and the groove pattern were correlated among central incisors, lateral incisors, and canines. This study may provide guidance for clinical design of labial grooves. PMID- 26901310 TI - Label-free capture of breast cancer cells spiked in buffy coats using carbon nanotube antibody micro-arrays. AB - We demonstrate the rapid and label-free capture of breast cancer cells spiked in buffy coats using nanotube-antibody micro-arrays. Single wall carbon nanotube arrays were manufactured using photo-lithography, metal deposition, and etching techniques. Anti-epithelial cell adhesion molecule (EpCAM) antibodies were functionalized to the surface of the nanotube devices using 1-pyrene-butanoic acid succinimidyl ester functionalization method. Following functionalization, plain buffy coat and MCF7 cell spiked buffy coats were adsorbed on to the nanotube device and electrical signatures were recorded for differences in interaction between samples. A statistical classifier for the 'liquid biopsy' was developed to create a predictive model based on dynamic time warping to classify device electrical signals that corresponded to plain (control) or spiked buffy coats (case). In training test, the device electrical signals originating from buffy versus spiked buffy samples were classified with ~100% sensitivity, ~91% specificity and ~96% accuracy. In the blinded test, the signals were classified with ~91% sensitivity, ~82% specificity and ~86% accuracy. A heatmap was generated to visually capture the relationship between electrical signatures and the sample condition. Confocal microscopic analysis of devices that were classified as spiked buffy coats based on their electrical signatures confirmed the presence of cancer cells, their attachment to the device and overexpression of EpCAM receptors. The cell numbers were counted to be ~1-17 cells per 5 MUl per device suggesting single cell sensitivity in spiked buffy coats that is scalable to higher volumes using the micro-arrays. PMID- 26901311 TI - Arabidopsis thaliana siRNA biogenesis mutants have the lower frequency of homologous recombination. AB - Small interfering RNAs (siRNAs) are involved in the regulation of plant development and response to stress. We have previously shown that mutants impaired in Dicer-like 2 (DCL2), DCL3 and DCL4, RDR2, RDR6 and NPRD1 are partially impaired in their response to stress and dcl2 and dcl3 plants are also impaired in transgenerational response to stress, including changes in homologous recombination frequency (HRF). Here, we have analyzed genome stability of dcl2, dcl3, dcl4, dcl2 dcl3, dcl2 dcl3 dcl4 and rdr6 mutants by measuring the non induced and the stress-induced recombination frequency. We found that all mutants had the lower spontaneous HRF. The analysis of strand breaks showed that all tested Arabidopsis mutants had a higher level of spontaneous strand breaks, suggesting that the lower HRF is not due to the unusually low level of breaks. Exposure to methyl methane sulfonate (MMS) resulted in an increase in the level of strand breaks in wild-type plants and a decrease in mutants. All mutants had the higher methylation of cytosines at CpG sites under non-induced conditions. Exposure to MMS resulted in a decrease in methylation level in wild-type plants and an increase in methylation in all dcl mutants. The expression of several DNA repair genes was altered in dcl4 plants under non-induced and induced conditions. Our data suggest that siRNA biogenesis may be essential for the maintenance of the genome stability and stress response in Arabidopsis. PMID- 26901312 TI - A Central Nervous System-Dependent Intron-Embedded Gene Encodes a Novel Murine Fyn Binding Protein. AB - The interplay between the nervous and immune systems is gradually being unraveled. We previously reported in the mouse the novel soluble immune system factor ISRAA, whose activation in the spleen is central nervous system-dependent. We also showed that ISRAA plays a role in modulating anti-infection immunity. Herein, we report the genomic description of the israa locus, along with some insights into the structure-function relationship of the protein. Our findings revealed that israa is nested within intron 6 of the mouse zmiz1 gene. Protein sequence analysis revealed a typical SH2 binding motif (Y102TEV), with Fyn being the most likely binding partner. Docking simulation showed a favorable conformation for the ISRAA-Fyn complex, with a specific binding mode for the binding of the YTEV motif to the SH2 domain. Experimental studies showed that in vitro, recombinant ISRAA is phosphorylated by Fyn at tyrosine 102. Cell transfection and pull-down experiments revealed Fyn as a binding partner of ISRAA in the EL4 mouse T-cell line. Indeed, we demonstrated that ISRAA downregulates T cell activation and the phosphorylation of an activation tyrosine (Y416) of Src family kinases in mouse splenocytes. Our observations highlight ISRAA as a novel Fyn binding protein that is likely to be involved in a signaling pathway driven by the nervous system. PMID- 26901313 TI - The Oropharyngeal Airway in Young Adults with Skeletal Class II and Class III Deformities: A 3-D Morphometric Analysis. AB - OBJECTIVES: 1) To determine the accuracy and reliability of an automated anthropometric measurement software for the oropharyngeal airway and 2) To compare the anthropometric dimensions of the oropharyngeal airway in skeletal class II and III deformity patients. METHODS: Cone-beam CT (CBCT) scans of 62 patients with skeletal class II or III deformities were used for this study. Volumetric, linear and surface area measurements retroglossal (RG) and retropalatal (RP) compartments of the oropharyngeal airway was measured with the 3dMDVultus software. Accuracy of automated anthropometric pharyngeal airway measurements was assessed using an airway phantom. RESULTS: The software was found to be reasonably accurate for measuring dimensions of air passages. The total oropharyngeal volume was significantly greater in the skeletal class III deformity group (16.7 +/- 9.04 mm3) compared with class II subjects (11.87 +/- 4.01 mm3). The average surface area of both the RG and RP compartments were significantly larger in the class III deformity group. The most constricted area in the RG and RP airway was significantly larger in individuals with skeletal class III deformity. The anterior-posterior (AP) length of this constriction was significantly greater in skeletal class III individuals in both compartments, whereas the width of the constriction was not significantly different between the two groups in both compartments. The RP compartment was larger but less uniform than the RG compartment in both skeletal deformities. CONCLUSION: Significant differences were observed in morphological characteristics of the oropharyngeal airway in individuals with skeletal class II and III deformities. This information may be valuable for surgeons in orthognathic treatment planning, especially for mandibular setback surgery that might compromise the oropharyngeal patency. PMID- 26901314 TI - Multiplex PCR and Next Generation Sequencing for the Non-Invasive Detection of Bladder Cancer. AB - BACKGROUND: Highly sensitive and specific urine-based tests to detect either primary or recurrent bladder cancer have proved elusive to date. Our ever increasing knowledge of the genomic aberrations in bladder cancer should enable the development of such tests based on urinary DNA. METHODS: DNA was extracted from urine cell pellets and PCR used to amplify the regions of the TERT promoter and coding regions of FGFR3, PIK3CA, TP53, HRAS, KDM6A and RXRA which are frequently mutated in bladder cancer. The PCR products were barcoded, pooled and paired-end 2 x 250 bp sequencing performed on an Illumina MiSeq. Urinary DNA was analysed from 20 non-cancer controls, 120 primary bladder cancer patients (41 pTa, 40 pT1, 39 pT2+) and 91 bladder cancer patients post-TURBT (89 cancer-free). RESULTS: Despite the small quantities of DNA extracted from some urine cell pellets, 96% of the samples yielded mean read depths >500. Analysing only previously reported point mutations, TERT mutations were found in 55% of patients with bladder cancer (independent of stage), FGFR3 mutations in 30% of patients with bladder cancer, PIK3CA in 14% and TP53 mutations in 12% of patients with bladder cancer. Overall, these previously reported bladder cancer mutations were detected in 86 out of 122 bladder cancer patients (70% sensitivity) and in only 3 out of 109 patients with no detectable bladder cancer (97% specificity). CONCLUSION: This simple, cost-effective approach could be used for the non invasive surveillance of patients with non-muscle-invasive bladder cancers harbouring these mutations. The method has a low DNA input requirement and can detect low levels of mutant DNA in a large excess of normal DNA. These genes represent a minimal biomarker panel to which extra markers could be added to develop a highly sensitive diagnostic test for bladder cancer. PMID- 26901317 TI - Efficiency of Portable Antennas for Detecting Passive Integrated Transponder Tags in Stream-Dwelling Salmonids. AB - Portable antennas have become an increasingly common technique for tracking fish marked with passive integrated transponder (PIT) tags. We used logistic regression to evaluate how species, fish length, and physical habitat characteristics influence portable antenna detection efficiency in stream dwelling brown trout (Salmo trutta), bull trout (Salvelinus confluentus), and redband trout (Oncorhynchus mykiss newberrii) marked with 12-mm PIT tags. We redetected 56% (20/36) of brown trout, 34% (68/202) of bull trout, and 33% (20/61) of redband trout after a recovery period of 21 to 46 hours. Models indicate support for length and species and minor support for percent boulder, large woody debris, and percent cobble as parameters important for describing variation in detection efficiency, although 95% confidence intervals for estimates were large. The odds of detecting brown trout (1.5 +/- 2.2 [mean +/- SE]) are approximately four times as high as bull trout (0.4 +/- 1.6) or redband trout (0.3 +/- 1.8) and species-specific differences may be related to length. Our reported detection efficiency for brown trout falls within the range of other studies, but is the first reported for bull trout and redband trout. Portable antennas may be a relatively unbiased way of redetecting varying sizes of all three salmonid species. PMID- 26901315 TI - Polyunsaturated Fatty Acids Attenuate Diet Induced Obesity and Insulin Resistance, Modulating Mitochondrial Respiratory Uncoupling in Rat Skeletal Muscle. AB - OBJECTIVES: Omega (omega)-3 polyunsaturated fatty acids (PUFA) are dietary compounds able to attenuate insulin resistance. Anyway, the precise actions of omega-3PUFAs in skeletal muscle are overlooked. We hypothesized that PUFAs, modulating mitochondrial function and efficiency, would ameliorate pro inflammatory and pro-oxidant signs of nutritionally induced obesity. STUDY DESIGN: To this aim, rats were fed a control diet (CD) or isocaloric high fat diets containing either omega-3 PUFA (FD) or lard (LD) for 6 weeks. RESULTS: FD rats showed lower weight, lipid gain and energy efficiency compared to LD-fed animals, showing higher energy expenditure and O2 consumption/CO2 production. Serum lipid profile and pro-inflammatory parameters in FD-fed animals were reduced compared to LD. Accordingly, FD rats exhibited a higher glucose tolerance revealed by an improved glucose and insulin tolerance tests compared to LD, accompanied by a restoration of insulin signalling in skeletal muscle. PUFAs increased lipid oxidation and reduced energy efficiency in subsarcolemmal mitochondria, and increase AMPK activation, reducing both endoplasmic reticulum and oxidative stress. Increased mitochondrial respiration was related to an increased mitochondriogenesis in FD skeletal muscle, as shown by the increase in PGC1-alpha and -beta. CONCLUSIONS: our data strengthened the association of high dietary omega3-PUFA intake with reduced mitochondrial energy efficiency in the skeletal muscle. PMID- 26901316 TI - Cost-Effectiveness Analysis of Six Strategies to Treat Recurrent Clostridium difficile Infection. AB - OBJECTIVE: To assess the cost-effectiveness of six treatment strategies for patients diagnosed with recurrent Clostridium difficile infection (CDI) in Canada: 1. oral metronidazole; 2. oral vancomycin; 3.oral fidaxomicin; 4. fecal transplantation by enema; 5. fecal transplantation by nasogastric tube; and 6. fecal transplantation by colonoscopy. PERSPECTIVE: Public insurer for all hospital and physician services. SETTING: Ontario, Canada. METHODS: A decision analytic model was used to model costs and lifetime health effects of each strategy for a typical patient experiencing up to three recurrences, over 18 weeks. Recurrence data and utilities were obtained from published sources. Cost data was obtained from published sources and hospitals in Toronto, Canada. The willingness-to-pay threshold was $50,000/QALY gained. RESULTS: Fecal transplantation by colonoscopy dominated all other strategies in the base case, as it was less costly and more effective than all alternatives. After accounting for uncertainty in all model parameters, there was an 87% probability that fecal transplantation by colonoscopy was the most beneficial strategy. If colonoscopy was not available, fecal transplantation by enema was cost-effective at $1,708 per QALY gained, compared to metronidazole. In addition, fecal transplantation by enema was the preferred strategy if the probability of recurrence following this strategy was below 8.7%. If fecal transplantation by any means was unavailable, fidaxomicin was cost-effective at an additional cost of $25,968 per QALY gained, compared to metronidazole. CONCLUSION: Fecal transplantation by colonoscopy (or enema, if colonoscopy is unavailable) is cost-effective for treating recurrent CDI in Canada. Where fecal transplantation is not available, fidaxomicin is also cost-effective. PMID- 26901318 TI - Gene Activation through the Modulation of Nucleoid Structures by a Horizontally Transferred Regulator, Pch, in Enterohemorrhagic Escherichia coli. AB - The horizontally transferred chromosomal segments, which are the main source of genetic diversity among bacterial pathogens, are bound by the nucleoid protein H NS, resulting in the formation of a nucleoprotein complex and the silencing of gene expression. The de-silencing or activation of virulence genes necessary for the colonization of enterohemorrhagic Escherichia coli is achieved mainly by the action of two regulators, Pch and Ler, which are encoded by horizontally transferred elements. Although Ler has been shown to activate transcription by counteracting H-NS silencing, the mechanism for Pch is poorly understood. We show here that Pch activates the LEE1 promoter and also enhances the Ler-mediated activation of other LEE promoters. Transcriptional activation was completely dependent on repression by the H-NS/StpA/Hha/YdgT complex, indicating that Pch derived activation was achieved by alleviating H-NS-mediated silencing. Expression of pch reduced the binding of H-NS at LEE1 promoter and altered the nucleoprotein complex. Furthermore, in vitro reconstruction of the protein-DNA complex on LEE1 promoter DNA confirmed the exclusive effect of Pch on H-NS binding. These results demonstrated that Pch is another anti-silencing regulator and a modulator of H-NS-containing nucleoprotein complexes. Thus, the anti silencing mechanism plays a key role in the coordinated regulation of virulence genes in EHEC. PMID- 26901319 TI - Phase Transitions in the Ruddlesden-Popper Phase Li2CaTa2O7: X-ray and Neutron Powder Thermodiffraction, TEM, Raman, and SHG Experiments. AB - The structure of the Ruddlesden-Popper layered perovskite Li2CaTa2O7, known for its high photocatalytic water activity since its discovery in 2008, is reinvestigated. This oxide has been characterized by powder X-ray and neutron thermodiffraction, TEM, second harmonic generation (SHG), and Raman experiments on powders and single crystals. It is shown that it undergoes two structural phase transitions (i) around 220 degrees C, mainly characterized by the progressive emergence of SHG signal at low temperatures, and (ii) at 660 degrees C, mainly characterized by changes of the temperature behavior of lattice parameters and by the emergence of Raman signals that linearly increase on decreasing temperature. It is shown by powder neutron diffraction profile refinements at RT, 400, and 800 degrees C that the space groups of the successive phases of Li2CaTa2O7 are the acentric Pna21 (RT <= T <= 220 degrees C), Pnma (220 degrees C <= T <= 660 degrees C), and Cmcm (T >= 660 degrees C). A soft mode associated with the transition to the highest symmetry for this structural arrangement (I4/mmm) is also found in the Raman spectra. All these transitions appear continuous: the high temperature ones can be attributed to progressive vanishings of the octahedra tiltings (displacives) while the transition in the vicinity of 220 degrees C from Pna21 to Pnma exhibits order disorder character. PMID- 26901321 TI - Precesarean Prophylactic Balloon Catheters for Suspected Placenta Accreta: A Randomized Controlled Trial. PMID- 26901320 TI - Liver-Enriched Gene 1, a Glycosylated Secretory Protein, Binds to FGFR and Mediates an Anti-stress Pathway to Protect Liver Development in Zebrafish. AB - Unlike mammals and birds, teleost fish undergo external embryogenesis, and therefore their embryos are constantly challenged by stresses from their living environment. These stresses, when becoming too harsh, will cause arrest of cell proliferation, abnormal cell death or senescence. Such organisms have to evolve a sophisticated anti-stress mechanism to protect the process of embryogenesis/organogenesis. However, very few signaling molecule(s) mediating such activity have been identified. liver-enriched gene 1 (leg1) is an uncharacterized gene that encodes a novel secretory protein containing a single domain DUF781 (domain of unknown function 781) that is well conserved in vertebrates. In the zebrafish genome, there are two copies of leg1, namely leg1a and leg1b. leg1a and leg1b are closely linked on chromosome 20 and share high homology, but are differentially expressed. In this report, we generated two leg1a mutant alleles using the TALEN technique, then characterized liver development in the mutants. We show that a leg1a mutant exhibits a stress dependent small liver phenotype that can be prevented by chemicals blocking the production of reactive oxygen species. Further studies reveal that Leg1a binds to FGFR3 and mediates a novel anti-stress pathway to protect liver development through enhancing Erk activity. More importantly, we show that the binding of Leg1a to FGFR relies on the glycosylation at the 70th asparagine (Asn(70) or N(70)), and mutating the Asn(70) to Ala(70) compromised Leg1's function in liver development. Therefore, Leg1 plays a unique role in protecting liver development under different stress conditions by serving as a secreted signaling molecule/modulator. PMID- 26901322 TI - In Reply. PMID- 26901323 TI - A Proactive Approach to Neonates Born at 23 Weeks of Gestation. PMID- 26901324 TI - In Reply. PMID- 26901325 TI - Disseminated Intravascular Coagulation Syndromes in Obstetrics. PMID- 26901326 TI - In Reply. PMID- 26901331 TI - Executive summary: Collaboration in Practice: Implementing Team-Based Care: Report of the American College of Obstetricians and Gynecologists' Task Force on Collaborative Practice. PMID- 26901332 TI - ACOG Committee Opinion No. 659 Summary: The Use of Vaginal Estrogen in Women With a History of Estrogen-Dependent Breast Cancer. AB - Cancer treatment should address female-specific survivorship issues, including the hypoestrogenic- related adverse effects of cancer therapies or of natural menopause in survivors. Systemic and vaginal estrogen are widely used for symptomatic relief of vasomotor symptoms, sexual dysfunction, and lower urinary tract infections in the general population. However, given that some types of cancer are hormone sensitive, there are safety concerns about the use of local hormone therapy in women who currently have breast cancer or have a history of breast cancer. Nonhormonal approaches are the first-line choices for managing urogenital symptoms or atrophy-related urinary symptoms experienced by women during or after treatment for breast cancer. Among women with a history of estrogen-dependent breast cancer who are experiencing urogenital symptoms, vaginal estrogen should be reserved for those patients who are unresponsive to nonhormonal remedies. The decision to use vaginal estrogen may be made in coordination with a woman's oncologist. Additionally, it should be preceded by an informed decision-making and consent process in which the woman has the information and resources to consider the benefits and potential risks of low dose vaginal estrogen. Data do not show an increased risk of cancer recurrence among women currently undergoing treatment for breast cancer or those with a personal history of breast cancer who use vaginal estrogen to relieve urogenital symptoms. PMID- 26901333 TI - ACOG Committee Opinion No. 660 Summary: Family Building Through Gestational Surrogacy. AB - Gestational surrogacy is an increasingly common form of family building that can allow individuals or a couple to become parents despite circumstances in which carrying a pregnancy is biologically impossible or medically contraindicated. The practice of gestational surrogacy involves a woman known as a gestational carrier who agrees to bear a genetically unrelated child with the help of assisted reproductive technologies for an individual or couple who intend(s) to be the legal and rearing parent(s), referred to as the intended parent(s). Obstetrician gynecologists may become involved in gestational surrogacy through caring for the gestational carrier or by caring for the intended parent(s). Although gestational surrogacy increases options for family building, this treatment also involves ethical, medical, psychosocial, and legal complexities that must be taken into account to minimize risks of adverse outcomes for the gestational carrier, intended parent(s), and resulting children. The purpose of this document is to provide an overview of gestational surrogacy and to describe the ethical responsibilities for obstetrician-gynecologists who take part in the care of women who participate in these arrangements. PMID- 26901334 TI - ACOG Committee Opinion No. 659: The Use of Vaginal Estrogen in Women With a History of Estrogen-Dependent Breast Cancer. AB - Cancer treatment should address female-specific survivorship issues, including the hypoestrogenic- related adverse effects of cancer therapies or of natural menopause in survivors. Systemic and vaginal estrogen are widely used for symptomatic relief of vasomotor symptoms, sexual dysfunction, and lower urinary tract infections in the general population. However, given that some types of cancer are hormone sensitive, there are safety concerns about the use of local hormone therapy in women who currently have breast cancer or have a history of breast cancer. Nonhormonal approaches are the first-line choices for managing urogenital symptoms or atrophy-related urinary symptoms experienced by women during or after treatment for breast cancer. Among women with a history of estrogen-dependent breast cancer who are experiencing urogenital symptoms, vaginal estrogen should be reserved for those patients who are unresponsive to nonhormonal remedies. The decision to use vaginal estrogen may be made in coordination with a woman's oncologist. Additionally, it should be preceded by an informed decision-making and consent process in which the woman has the information and resources to consider the benefits and potential risks of low dose vaginal estrogen. Data do not show an increased risk of cancer recurrence among women currently undergoing treatment for breast cancer or those with a personal history of breast cancer who use vaginal estrogen to relieve urogenital symptoms. PMID- 26901335 TI - ACOG Committee Opinion No. 660: Family Building Through Gestational Surrogacy. AB - Gestational surrogacy is an increasingly common form of family building that can allow individuals or a couple to become parents despite circumstances in which carrying a pregnancy is biologically impossible or medically contraindicated. The practice of gestational surrogacy involves a woman known as a gestational carrier who agrees to bear a genetically unrelated child with the help of assisted reproductive technologies for an individual or couple who intend(s) to be the legal and rearing parent(s), referred to as the intended parent(s). Obstetrician gynecologists may become involved in gestational surrogacy through caring for the gestational carrier or by caring for the intended parent(s). Although gestational surrogacy increases options for family building, this treatment also involves ethical, medical, psychosocial, and legal complexities that must be taken into account to minimize risks of adverse outcomes for the gestational carrier, intended parent(s), and resulting children. The purpose of this document is to provide an overview of gestational surrogacy and to describe the ethical responsibilities for obstetrician-gynecologists who take part in the care of women who participate in these arrangements. PMID- 26901337 TI - Segmental colitis caused by idiopathic myointimal hyperplasia of mesenteric veins. AB - Diseases causing colonic ischemia may be mistaken with other causes of segmental colitis such as inflammatory bowel disease, especially in young patients. The authors present the case of a 47-year-old male with severe proctosigmoiditis. Assessment excluded infectious causes, thrombophilia and systemic vasculitis. The initial histological specimen was suggestive of inflammatory bowel disease and therapy was initiated with intravenous steroids and, at day 5, infliximab, with no response. The patient was proposed for surgery. Pathological examination of the surgical specimen revealed an idiopathic myointimal hyperplasia of mesenteric veins, a rare entity exhibiting necrotizing phlebitis with rapid progression to segmental necrosis in the rectosigmoid colon. In this paper the authors discuss the differential diagnosis of proctosigmoiditis in young ages and the approach to this exceptionally rare ischemic entity. PMID- 26901336 TI - Foot-and-mouth disease virus structural protein VP3 degrades Janus kinase 1 to inhibit IFN-gamma signal transduction pathways. AB - Foot-and-mouth disease is a highly contagious viral disease of cloven-hoofed animals that is caused by foot-and-mouth disease virus (FMDV). To replicate efficiently in vivo, FMDV has evolved methods to circumvent host antiviral defense mechanisms, including those induced by interferons (IFNs). Previous research has focused on the effect of FMDV L(pro) and 3C(pro) on type I IFNs. In this study, FMDV VP3 was found to inhibit type II IFN signaling pathways. The overexpression of FMDV VP3 inhibited the IFN-gamma-triggered phosphorylation of STAT1 at Tyr701 and the subsequent expression of downstream genes. Mechanistically, FMDV VP3 interacted with JAK1/2 and inhibited the tyrosine phosphorylation, dimerization and nuclear accumulation of STAT1. FMDV VP3 also disrupted the assembly of the JAK1 complex and degraded JAK1 but not JAK2 via a lysosomal pathway. Taken together, the results reveal a novel mechanism used by which FMDV VP3 counteracts the type II IFN signaling pathways. PMID- 26901340 TI - The effects of renal denervation on resistant hypertension patients: a meta analysis. AB - We carried out this meta-analysis to assess the effects of renal denervation (RDN) on resistant hypertension patients. According to the collaborative review group search strategy, we searched MEDLINE (1996 to 2015.10); EBCO (1996 to 2015.10) and CNKI. A meta-analysis was carried out using RevMan 5.0. We identified 11 reports that fulfilled the inclusion criteria for our review. Controlled trials reporting systolic blood pressure (SBP), diastolic blood pressure in RDN, and control groups at the 6-month follow-up in patients with resistant hypertension were systematically reviewed. Pooled analysis of all 11 included studies showed significant reductions in SBP (weighted mean difference 13.9 mmHg, 95% confidence interval -21.17 to -6.63, P=0.00025, I=93%) and diastolic blood pressure (weighted mean difference -4.41 mmHg, 95% confidence interval -6.95 to -1.88, P=0.004, I=90%) compared with the control group at the 6 month follow-up. Six controlled trials reported specific values of ambulatory SBP that showed no significant difference between two groups. It has also been found that RDN has benefits in protecting cardiac and renal function compared with the control group without increasing adverse events. In conclusion, this meta analysis shows that RDN is superior to the control group in lowering office blood pressure rather than ambulatory SBP, and might have other potential benefits to protect heart and renal function. PMID- 26901338 TI - Predicting Progression from Mild Cognitive Impairment to Alzheimer's Dementia Using Clinical, MRI, and Plasma Biomarkers via Probabilistic Pattern Classification. AB - BACKGROUND: Individuals with mild cognitive impairment (MCI) have a substantially increased risk of developing dementia due to Alzheimer's disease (AD). In this study, we developed a multivariate prognostic model for predicting MCI-to dementia progression at the individual patient level. METHODS: Using baseline data from 259 MCI patients and a probabilistic, kernel-based pattern classification approach, we trained a classifier to distinguish between patients who progressed to AD-type dementia (n = 139) and those who did not (n = 120) during a three-year follow-up period. More than 750 variables across four data sources were considered as potential predictors of progression. These data sources included risk factors, cognitive and functional assessments, structural magnetic resonance imaging (MRI) data, and plasma proteomic data. Predictive utility was assessed using a rigorous cross-validation framework. RESULTS: Cognitive and functional markers were most predictive of progression, while plasma proteomic markers had limited predictive utility. The best performing model incorporated a combination of cognitive/functional markers and morphometric MRI measures and predicted progression with 80% accuracy (83% sensitivity, 76% specificity, AUC = 0.87). Predictors of progression included scores on the Alzheimer's Disease Assessment Scale, Rey Auditory Verbal Learning Test, and Functional Activities Questionnaire, as well as volume/cortical thickness of three brain regions (left hippocampus, middle temporal gyrus, and inferior parietal cortex). Calibration analysis revealed that the model is capable of generating probabilistic predictions that reliably reflect the actual risk of progression. Finally, we found that the predictive accuracy of the model varied with patient demographic, genetic, and clinical characteristics and could be further improved by taking into account the confidence of the predictions. CONCLUSIONS: We developed an accurate prognostic model for predicting MCI-to dementia progression over a three-year period. The model utilizes widely available, cost-effective, non-invasive markers and can be used to improve patient selection in clinical trials and identify high-risk MCI patients for early treatment. PMID- 26901339 TI - Chilling-Mediated DNA Methylation Changes during Dormancy and Its Release Reveal the Importance of Epigenetic Regulation during Winter Dormancy in Apple (Malus x domestica Borkh.). AB - Winter dormancy is a well known mechanism adopted by temperate plants, to mitigate the chilling temperature of winters. However, acquisition of sufficient chilling during winter dormancy ensures the normal phenological traits in subsequent growing period. Thus, low temperature appears to play crucial roles in growth and development of temperate plants. Apple, being an important temperate fruit crop, also requires sufficient chilling to release winter dormancy and normal phenological traits, which are often associated with yield and quality of fruits. DNA cytosine methylation is one of the important epigenetic modifications which remarkably affect the gene expression during various developmental and adaptive processes. In present study, methylation sensitive amplified polymorphism was employed to assess the changes in cytosine methylation during dormancy, active growth and fruit set in apple, under differential chilling conditions. Under high chill conditions, total methylation was decreased from 27.2% in dormant bud to 21.0% in fruit set stage, while no significant reduction was found under low chill conditions. Moreover, the demethylation was found to be decreased, while methylation increased from dormant bud to fruit set stage under low chill as compared to high chill conditions. In addition, RNA-Seq analysis showed high expression of DNA methyltransferases and histone methyltransferases during dormancy and fruit set, and low expression of DNA glcosylases during active growth under low chill conditions, which was in accordance with changes in methylation patterns. The RNA-Seq data of 47 genes associated with MSAP fragments involved in cellular metabolism, stress response, antioxidant system and transcriptional regulation showed correlation between methylation and their expression. Similarly, bisulfite sequencing and qRT-PCR analysis of selected genes also showed correlation between gene body methylation and gene expression. Moreover, significant association between chilling and methylation changes was observed, which suggested that chilling acquisition during dormancy in apple is likely to affect the epigenetic regulation through DNA methylation. PMID- 26901341 TI - Analysis of Trigger Factors in Episodic Migraineurs Using a Smartphone Headache Diary Applications. AB - BACKGROUND: Various stimuli can trigger migraines in susceptible individuals. We examined migraine trigger factors by using a smartphone headache diary application. METHOD: Episodic migraineurs who agreed to participate in our study downloaded smartphone headache diary application, which was designed to capture the details regarding headache trigger factors and characteristics for 3 months. The participants were asked to access the smartphone headache diary application daily and to confirm the presence of a headache and input the types of trigger factors. RESULTS: Sixty-two participants kept diary entries until the end of the study. The diary data for 4,579 days were analyzed. In this data set, 1,099 headache days (336 migraines, 763 non-migraine headaches) were recorded; of these, 772 headache events had with trigger factors, and 327 events did not have trigger factors. The common trigger factors that were present on headache days included stress, fatigue, sleep deprivation, hormonal changes, and weather changes. The likelihood of a headache trigger was 57.7% for stress, 55.1% for sleep deprivation, 48.5% for fatigue, and 46.5% for any trigger. The headaches with trigger factors were associated with greater pain intensity (p<0.001), headache-related disability (p<0.001), abortive medication use (p = 0.02), and the proportion of migraine (p < 0.001), relative to those without trigger factors. Traveling (odd ratios [OR]: 6.4), hormonal changes (OR: 3.5), noise (OR: 2.8), alcohol (OR: 2.5), overeating (OR: 2.4), and stress (OR:1.8) were significantly associated with migraines compared to non-migraine headaches. The headaches that were associated with hormonal changes or noise were more often migraines, regardless of the preventive medication. The headaches due to stress, overeating, alcohol, and traveling were more often migraines without preventive medication, but it was not evident with preventive medication. CONCLUSION: Smartphone headache diary application is an effective tool to assess migraine trigger factors. The headaches with trigger factors had greater severity or migraine features. The type of triggers and the presence of preventive medication influenced the headache characteristics; hence, an investigation of trigger factors would be helpful in understanding migraine occurrences. PMID- 26901342 TI - THC:CBD in Daily Practice: Available Data from UK, Germany and Spain. AB - BACKGROUND: From the time Sativex (THC:CBD) oromucosal spray first became available in European Union countries in 2010 for the management of treatment resistant multiple sclerosis (MS) spasticity, data from daily practice have been collected through various projects. METHODS: A retrospective registry study and a prospective safety study of THC:CBD oromucosal spray are reported. RESULTS: The most recent analysis of a retrospective registry established in the United Kingdom (UK), Germany and Switzerland, which collected safety data on more than 900 patients, has indicated a positive risk-benefit profile for THC:CBD oromucosal spray during long-term use. Long-term continuation rates were 68% (mean follow-up time 1 year) and the mean dose was 5.4 sprays/day. No new safety concerns were identified, and adverse events of special interest for a cannabis based medicine were limited. The UK registry has since been closed but remains open in Germany and Switzerland. A prospective safety study undertaken in Spain involved 207 patients from 13 specialized MS centres who had been prescribed THC:CBD oromucosal spray. The findings aligned closely with the UK/German/Swiss registry data in terms of 1-year continuation rates (64.7%), mean daily dose (6.6 sprays/day) and safety profile, including no evidence of addiction, abuse or misuse. CONCLUSIONS: The homogeneity between these observational studies supports the interest in THC:CBD oromucosal spray for management of MS spasticity in daily practice. PMID- 26901343 TI - THC:CBD Observational Study Data: Evolution of Resistant MS Spasticity and Associated Symptoms. AB - BACKGROUND: The prospective observational MObility ImproVEment (MOVE) 2 study is collecting real-life clinical outcomes data on patients with treatment-resistant multiple sclerosis (MS) spasticity treated with THC:CBD oromucosal spray in routine clinical practice. The MOVE 2 study has been ongoing in Italy, involving more than 30 MS centres across the country, since 2013. METHODS: Web-based real time data collection techniques are combined with traditional patients' diaries to capture a wide spectrum of outcomes associated with this innovative cannabis based medication. After surpassing the recruitment threshold of 300 patients, an interim analysis was performed to determine whether the data collected to date align with those from MOVE 2-Germany and the largest phase III randomized controlled trial (RCT) of THC:CBD oromucosal spray. RESULTS: In the Italian cohort, THC:CBD oromucosal spray was added mainly to oral baclofen. Similar to MOVE 2-Germany, during 3 months' observation, treatment discontinuations were limited and patients recorded meaningful improvements on the patient-based 0-10 numerical rating scale and physician-rated modified Ashworth scale at mean daily doses that were about one-third lower than those used in the RCT. Also, similar to MOVE 2-Germany, the proportion of patients reporting adverse events was about one-third of the rate recorded in the RCT. CONCLUSIONS: While MOVE 2-Italy continues, this interim analysis has enabled us to better define the place in therapy of THC:CBD oromucosal spray within the context of daily management of our patients with MS spasticity. PMID- 26901344 TI - Health Authorities Data Collection of THC:CBD Oromucosal Spray (L'Agenzia Italiana del Farmaco Web Registry): Figures after 1.5 Years. AB - BACKGROUND: In Italy, all prescriptions for THC:CBD oromucosal spray for treatment of multiple sclerosis (MS) spasticity are linked to the official Agenzia Italiana del Farmaco (AIFA) web-based registry, which tracks the effectiveness and tolerability of medications in a prospective and observational manner. METHODS: AIFA e-registry data for THC:CBD oromucosal spray collected between January 2014 and February 2015 for 1,534 patients from 30 large Italian specialized MS centres were compiled. Patients had a long disease history (17.6 +/- 8.6 years) and significant impairment (mean Expanded Disability Status Scale score 6.4 +/- 1.2). MS spasticity was evaluated using the 0-10 numerical rating scale (NRS). RESULTS: After the first month titration and trial period, 61.9% of patients achieved sufficient improvement in spasticity (>=20% NRS) to qualify for continued treatment. After 6 months, clinically meaningful >=30% NRS improvement was recorded in 40.2% of patients continuing with treatment. Spasticity associated symptoms such as cramps and nocturnal spasms improved in most responding patients. Mean reported doses of THC:CBD oromucosal spray (6.2-6.7 sprays/day) were lower than those reported in clinical trials. Adverse events (mainly mild to moderate) were reported by 15% of patients; no new safety concerns beyond the approved label were identified. CONCLUSION: The results of the AIFA e-registry analysis align with those of other THC:CBD observational projects and reaffirm the characteristics of this therapeutic option in the management of treatment-resistant MS spasticity, a frequently overlooked symptom. PMID- 26901346 TI - Heavy-Tailed Fluctuations in the Spiking Output Intensity of Semiconductor Lasers with Optical Feedback. AB - Although heavy-tailed fluctuations are ubiquitous in complex systems, a good understanding of the mechanisms that generate them is still lacking. Optical complex systems are ideal candidates for investigating heavy-tailed fluctuations, as they allow recording large datasets under controllable experimental conditions. A dynamical regime that has attracted a lot of attention over the years is the so-called low-frequency fluctuations (LFFs) of semiconductor lasers with optical feedback. In this regime, the laser output intensity is characterized by abrupt and apparently random dropouts. The statistical analysis of the inter-dropout-intervals (IDIs) has provided many useful insights into the underlying dynamics. However, the presence of large temporal fluctuations in the IDI sequence has not yet been investigated. Here, by applying fluctuation analysis we show that the experimental distribution of IDI fluctuations is heavy tailed, and specifically, is well-modeled by a non-Gaussian stable distribution. We find a good qualitative agreement with simulations of the Lang-Kobayashi model. Moreover, we uncover a transition from a less-heavy-tailed state at low pump current to a more-heavy-tailed state at higher pump current. Our results indicate that fluctuation analysis can be a useful tool for investigating the output signals of complex optical systems; it can be used for detecting underlying regime shifts, for model validation and parameter estimation. PMID- 26901345 TI - Hyperinsulinemic Hypoglycemia after Bariatric Surgery: Diagnosis and Management Experience from a Spanish Multicenter Registry. AB - BACKGROUND: Severe postprandial hypoglycemia after bariatric surgery is a rare but invalidating complication. Our aim was to describe the different tests performed for its diagnosis and their outcomes as well as the response to the prescribed pharmacological and surgical treatments. METHODS: Multicenter, retrospective systematic review of cases with recurrent severe postprandial hypoglycemia. RESULTS: Over 11 years of follow-up, 22 patients were identified. The test most used to provoke hypoglycemia was the oral glucose load test followed by the mixed meal test which was the least standardized test. With pharmacological treatment, 3 patients were symptom-free (with octreotide) and in 12 patients hypoglycemic episodes were attenuated. Seven patients had persistent hypoglycemic episodes and underwent surgery. Partial pancreatectomy was performed in 3 patients who had positive selective arterial calcium stimulation, and nesidioblastosis was confirmed in 2 patients. Reconversion to normal anatomy was performed in 3 patients, and 1 patient underwent a resection of the 'candy cane' roux limb, with resolution of hypoglycemia in all cases. CONCLUSIONS: There is high heterogeneity in the evaluation and treatment options for postoperative hypoglycemia. In patients that do not respond to pharmacological treatment, reconstruction of gastrojejunal continuity may be the safest and most successful procedure. PMID- 26901347 TI - miRNA-221-3p Enhances the Secretion of Interleukin-4 in Mast Cells through the Phosphatase and Tensin Homolog/p38/Nuclear Factor-kappaB Pathway. AB - Mast cells play a central role in asthma. Moreover, serum miRNA-221-3p (miR-221) has been shown to be markedly increased in children with asthma. In the current study, we aimed to examine miR-221 expression in an asthma model and elucidate the mechanisms regulating interleukin (IL)-4 secretion in mast cells. Using polymerase chain reaction, we found that miR-221 was upregulated in a murine asthma model and in P815 mast cells after lipopolysaccharide (LPS) stimulation. Moreover, miR-221 upregulated IL-4 secretion from P815 cells, as shown by enzyme linked immunosorbent assays. Bioinformatics analysis, luciferase reporter gene assays, and western blotting showed that phosphatase and tensin homolog (PTEN) was a target of miR-221 and could block IL-4 secretion stimulated by miR-221. The phosphorylation of p38 (protein) and activity of nuclear factor-kappaB (NF kappaB) were increased after overexpression of miR-221, as shown by electrophoretic mobility shift assays. Finally, treatment with specific inhibitors could block IL-4 secretion. In conclusion, miR-221, which was overexpressed in a murine asthma model, stimulated IL-4 secretion in mast cells through a pathway involving PTEN, p38, and NF-kappaB. PMID- 26901348 TI - Substance P Inhibits Hyperosmotic Stress-Induced Apoptosis in Corneal Epithelial Cells through the Mechanism of Akt Activation and Reactive Oxygen Species Scavenging via the Neurokinin-1 Receptor. AB - Hyperosmolarity has been recognized as an important pathological factor in dry eye leading to ocular discomfort and damage. As one of the major neuropeptides of corneal innervation, substance P (SP) has been shown to possess anti-apoptotic effects in various cells. The aim of this study was to determine the capacity and mechanism of SP against hyperosmotic stress-induced apoptosis in cultured corneal epithelial cells. The cells were exposed to hyperosmotic stress by the addition of high glucose in the presence or absence of SP. The results showed that SP inhibited hyperosmotic stress-induced apoptosis of mouse corneal epithelial cells. Moreover, SP promoted the recovery of phosphorylated Akt level, mitochondrial membrane potential, Ca2+ contents, intracellular reactive oxygen species (ROS) and glutathione levels that impaired by hyperosmotic stress. However, the antiapoptotic capacity of SP was partially suppressed by Akt inhibitor or glutathione depleting agent, while the neurokinin-1 (NK-1) receptor antagonist impaired Akt activation and ROS scavenging that promoted by SP addition. In conclusion, SP protects corneal epithelial cells from hyperosmotic stress-induced apoptosis through the mechanism of Akt activation and ROS scavenging via the NK-1 receptor. PMID- 26901350 TI - Multilayer Black Phosphorus as a Versatile Mid-Infrared Electro-optic Material. AB - We investigate the electro-optic properties of black phosphorus (BP) thin films for optical modulation in the mid-infrared frequencies. Our calculation indicates that an applied out-of-plane electric field may lead to red-, blue-, or bidirectional shift in BP's absorption edge. This is due to the interplay between the field-induced quantum-confined Franz-Keldysh effect and the Pauli-blocked Burstein-Moss shift. The relative contribution of the two electro-absorption mechanisms depends on doping range, operating wavelength, and BP film thickness. For proof-of concept, simple modulator configuration with BP overlaid over a silicon nanowire is studied. Simulation results show that operating BP in the quantum-confined Franz-Keldysh regime can improve the maximal attainable absorption as well as power efficiency compared to its graphene counterpart. PMID- 26901349 TI - Neuroprotective Role of Intermittent Hypobaric Hypoxia in Unpredictable Chronic Mild Stress Induced Depression in Rats. AB - Hypoxic exposure results in several pathophysiological conditions associated with nervous system, these include acute and chronic mountain sickness, loss of memory, and high altitude cerebral edema. Previous reports have also suggested the role of hypoxia in pathogenesis of depression and related psychological conditions. On the other hand, sub lethal intermittent hypoxic exposure induces protection against future lethal hypoxia and may have beneficial effect. Therefore, the present study was designed to explore the neuroprotective role of intermittent hypobaric hypoxia (IHH) in Unpredictable Chronic Mild Stress (UCMS) induced depression like behaviour in rats. The IHH refers to the periodic exposures to hypoxic conditions interrupted by the normoxic or lesser hypoxic conditions. The current study examines the effect of IHH against UCMS induced depression, using elevated plus maze (EPM), open field test (OFT), force swim test (FST), as behavioural paradigm and related histological and molecular approaches. The data indicated the UCMS induced depression like behaviour as evident from decreased exploration activity in OFT with increased anxiety levels in EPM, and increased immobility time in the FST; whereas on providing the IHH (5000m altitude, 4hrs/day for two weeks) these behavioural changes were ameliorated. The morphological and molecular studies also validated the neuroprotective effect of IHH against UCMS induced neuronal loss and decreased neurogenesis. Here, we also explored the role of Brain-Derived Neurotrophic Factor (BDNF) in anticipatory action of IHH against detrimental effect of UCMS as upon blocking of BDNF-TrkB signalling the beneficial effect of IHH was nullified. Taken together, the findings of our study demonstrate that the intermittent hypoxia has a therapeutic potential similar to an antidepressant in animal model of depression and could be developed as a preventive therapeutic option against this pathophysiological state. PMID- 26901351 TI - A componential emotion approach for the assessment of emotional awareness in youth. AB - The Levels of Emotional Awareness Scale for Children (LEAS-C) is a performance based instrument that assesses emotional awareness in the structure of written responses to a set of real-life scenarios. While it is theoretically expected that emotional awareness develops with age, virtually no age differences have been established with the LEAS-C. The present study investigated whether an adaptation of the instructions and scoring procedure on the basis of the componential emotion approach could improve the validity of the LEAS-C and reveal the theoretically expected age differences. An adapted LEAS-C was administered to a sample of 574 children and adolescents and scored with the original and a new componential scoring procedure. An acceptable reliability for the original and a good reliability and a high interrater reliability for the componential scoring procedure were observed. Multigroup confirmatory factor analyses showed measurement invariance of factor loadings and intercepts across children (8 to 12 years) and adolescents (13 to 16 years) for all tested models, for both scoring procedures. A one-factor model fitted well for the total scores and self and other scores for both scoring procedures. The pattern of relationships with alexithymia, emotional intelligence, intelligence, personality, and social and emotional impairment as well as gender differences were comparable with prior research. Furthermore, the expected relationship with age was found, with stronger correlations for the componential than the original scoring procedure. In conclusion, analyses of the reliability, internal structure, and nomological network supported the adaptations of the LEAS-C on the basis of the componential emotion approach. (PsycINFO Database Record PMID- 26901352 TI - Anatomical Grading for Metabolic Activity of Brown Adipose Tissue. AB - BACKGROUND: Recent advances in obesity research suggest that BAT activity, or absence thereof, may be an important factor in the growing epidemic of obesity and its manifold complications. It is thus important to assess larger populations for BAT-activating and deactivating factors. 18FDG-PET/CT is the standard method to detect and quantify metabolic BAT activity, however, the manual measurement is not suitable for large studies due to its time-consuming nature and poor reproducibility across different software and devices. METHODOLOGY/MAIN FINDINGS: In a retrospective study, 1060 consecutive scans of 1031 patients receiving a diagnostic 18FDG-PET/CT were examined for the presence of active BAT. Patients were classified according to a 3-tier system (supraclavicular, mediastinal, infradiaphragmatic) depending on the anatomical location of their active BAT depots, with the most caudal location being the decisive factor. The metabolic parameters (maximum activity, total volume and total glycolysis) were measured on a standard PET/CT workstation. Mean age of the population was 60+/-14.6y. 41.61% of patients were female. Metabolically active BAT was found in 53 patients (5.1%). Female, younger and leaner patients tended to have more active BAT, higher metabolic activity and more caudally active BAT. In total, 15 patients showed only supraclavicular, 27 additional mediastinal, and 11 infradiaphragmal activity. Interestingly, the activation of BAT always followed a cranio-caudal gradient. This anatomical pattern correlated with age and BMI as well as with all metabolic parameters, including maximum and total glycolysis (p<0.001). CONCLUSION: Based on our data we propose a simple method to grade or quantify the degree of BAT amount/activity in patients based on the most caudally activated depot. As new modalities for BAT visualization may arise in the future, this system would allow direct comparability with other modalities, in contrary to the PET-metrics, which are restricted to 18FDG-PET/CT. PMID- 26901353 TI - Dynamic Drusen Remodelling in Participants of the Nutritional AMD Treatment-2 (NAT-2) Randomized Trial. AB - PURPOSE: To evaluate the dynamic remodeling of drusen in subjects with unilateral neovascular age-related macular degeneration (AMD) receiving a three-year course of oral docosahexaenoic acid (DHA) or placebo. SETTING: Institutional setting. METHODS: Three hundred subjects with age-related maculopathy and neovascular AMD in the fellow eye were randomly assigned to receive either 840 mg/day DHA or placebo for 3 years. Main outcome measures of this post-hoc sub-group analysis were progression of drusen number, total diameter, and total area on fundus photography, and their association with DHA supplementation, socio-demographic and genetic characteristics. RESULTS: Drusen progression was analyzed in 167 subjects that did not develop CNV (87 that received DHA and 80 that received placebo). None of the drusen remodeling outcomes were significantly associated with DHA supplementation. Total drusen diameter reduction in the inner subfield was significantly associated with age (older patients: r = -0.17; p = 0.003). Women showed a tendency to decreased total drusen diameter in the inner subfield with CFH polymorphism (p = 0.03), where women with TT genotype tended to have a greater reduction in drusen diameter than other genotypes (CC and CT). Drusen area in the inner subfield was more reduced in older patients (r = -0.17) and in women (p = 0.01). Drusen number showed no significant trends. CONCLUSIONS: Dynamic drusen remodeling with net reduction in drusen load over three years was found in patients with exudative AMD in one eye and drusen in the other eye (study-eye). This reduction was correlated with increased age and female gender, and showed a tendency to be influenced by CFH genotype, but did not appear to be affected by DHA supplementation. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN98246501. PMID- 26901356 TI - Retraction of Chen et al. (2012) 16:952-956; DOI: 10.1089/gmtb.2012.0033. PMID- 26901354 TI - Progress and prospects for L2-based human papillomavirus vaccines. AB - Human papillomavirus (HPV) is a worldwide public health problem, particularly in resource-limited countries. Fifteen high-risk genital HPV types are sexually transmitted and cause 5% of all cancers worldwide, primarily cervical, anogenital and oropharyngeal carcinomas. Skin HPV types are generally associated with benign disease, but a subset is linked to non-melanoma skin cancer. Licensed HPV vaccines based on virus-like particles (VLPs) derived from L1 major capsid antigen of key high risk HPVs are effective at preventing these infections but do not cover cutaneous types and are not therapeutic. Vaccines targeting L2 minor capsid antigen, some using capsid display, adjuvant and fusions with early HPV antigens or Toll-like receptor agonists, are in development to fill these gaps. Progress and challenges with L2-based vaccines are summarized. PMID- 26901355 TI - A Non-Destructive Method for Distinguishing Reindeer Antler (Rangifer tarandus) from Red Deer Antler (Cervus elaphus) Using X-Ray Micro-Tomography Coupled with SVM Classifiers. AB - Over the last decade, biomedical 3D-imaging tools have gained widespread use in the analysis of prehistoric bone artefacts. While initial attempts to characterise the major categories used in osseous industry (i.e. bone, antler, and dentine/ivory) have been successful, the taxonomic determination of prehistoric artefacts remains to be investigated. The distinction between reindeer and red deer antler can be challenging, particularly in cases of anthropic and/or taphonomic modifications. In addition to the range of destructive physicochemical identification methods available (mass spectrometry, isotopic ratio, and DNA analysis), X-ray micro-tomography (micro-CT) provides convincing non-destructive 3D images and analyses. This paper presents the experimental protocol (sample scans, image processing, and statistical analysis) we have developed in order to identify modern and archaeological antler collections (from Isturitz, France). This original method is based on bone microstructure analysis combined with advanced statistical support vector machine (SVM) classifiers. A combination of six microarchitecture biomarkers (bone volume fraction, trabecular number, trabecular separation, trabecular thickness, trabecular bone pattern factor, and structure model index) were screened using micro-CT in order to characterise internal alveolar structure. Overall, reindeer alveoli presented a tighter mesh than red deer alveoli, and statistical analysis allowed us to distinguish archaeological antler by species with an accuracy of 96%, regardless of anatomical location on the antler. In conclusion, micro-CT combined with SVM classifiers proves to be a promising additional non-destructive method for antler identification, suitable for archaeological artefacts whose degree of human modification and cultural heritage or scientific value has previously made it impossible (tools, ornaments, etc.). PMID- 26901357 TI - Personalized Medicine: Review and Perspectives of Promising Baseline EEG Biomarkers in Major Depressive Disorder and Attention Deficit Hyperactivity Disorder. AB - Personalized medicine in psychiatry is in need of biomarkers that resemble central nervous system function at the level of neuronal activity. Electroencephalography (EEG) during sleep or resting-state conditions and event related potentials (ERPs) have not only been used to discriminate patients from healthy subjects, but also for the prediction of treatment outcome in various psychiatric diseases, yielding information about tailored therapy approaches for an individual. This review focuses on baseline EEG markers for two psychiatric conditions, namely major depressive disorder and attention deficit hyperactivity disorder. It covers potential biomarkers from EEG sleep research and vigilance regulation, paroxysmal EEG patterns and epileptiform discharges, quantitative EEG features within the EEG main frequency bands, connectivity markers and ERP components that might help to identify favourable treatment outcome. Further, the various markers are discussed in the context of their potential clinical value and as research domain criteria, before giving an outline for future studies that are needed to pave the way to an electrophysiological biomarker-based personalized medicine. PMID- 26901359 TI - Connection between Hybrid Functionals and Importance of the Local Density Approximation. AB - The exchange-correlation (XC) local density approximation (LDA) is the original density functional used to investigate the electronic structure of molecules and solids within the formulation of Kohn and Sham. The LDA is fundamental for the development of density-functional approximations. In this work we consider the generalized Kohn-Sham (GKS) theory of hybrid functionals. The GKS formalism is an extension of the Kohn-Sham theory for electronic ground states and leads to a vast set of alternative density functionals, which can be estimated by the LDA and related methods. Herein we study auxiliary electronic systems with parametrized interactions and derive (i) a set of exact equations relating the GKS XC energies in the parameter space and (ii) a formal relation between the parameters and the standard XC derivative discontinuity. In view of the new results and previously reported findings, we discuss why the inclusion of Fock exchange, and its long-range-corrected form (in the ground-state calculations and in linear-response Kohn-Sham equations), dominate over the generalized gradient corrections to enhance the quality of the fundamental gap and to enhance excitation-energy estimations. As an example, we show that the adiabatic CAM-LDA0 (a functional with 1/4 global and 1/2 long-range Hartree-Fock interaction, respectively, a range separation factor of 1/3, and pure LDA exchange and correlation) works for electronic excitations as well as the adiabatic CAM-B3LYP functional. PMID- 26901358 TI - Risk of nosocomial respiratory syncytial virus infection and effectiveness of control measures to prevent transmission events: a systematic review. AB - Respiratory syncytial virus (RSV) causes a significant public health burden, and outbreaks among vulnerable patients in hospital settings are of particular concern. We reviewed published and unpublished literature from hospital settings to assess: (i) nosocomial RSV transmission risk (attack rate) during outbreaks, (ii) effectiveness of infection control measures. We searched the following databases: MEDLINE, EMBASE, CINAHL, Cochrane Library, together with key websites, journals and grey literature, to end of 2012. Risk of bias was assessed using the Cochrane risk of bias tool or Newcastle-Ottawa scale. A narrative synthesis was conducted. Forty studies were included (19 addressing research question one, 21 addressing question two). RSV transmission risk varied by hospital setting; 6-56% (median: 28.5%) in neonatal/paediatric settings (n = 14), 6-12% (median: 7%) in adult haematology and transplant units (n = 3), and 30-32% in other adult settings (n = 2). For question two, most studies (n = 13) employed multi component interventions (e.g. cohort nursing, personal protective equipment (PPE), isolation), and these were largely reported to be effective in reducing nosocomial transmission. Four studies examined staff PPE; eye protection appeared more effective than gowns and masks. One study reported on RSV prophylaxis for patients (RSV-Ig/palivizumab); there was no statistical evidence of effectiveness although the sample size was small. Overall, risk of bias for included studies tended to be high. We conclude that RSV transmission risk varies widely during hospital outbreaks. Although multi-component control strategies appear broadly successful, further research is required to disaggregate the effectiveness of individual components including the potential role of palivizumab prophylaxis. PMID- 26901360 TI - Validating new diagnostic imaging criteria for primary progressive aphasia via anatomical likelihood estimation meta-analyses. AB - Recently, diagnostic clinical and imaging criteria for primary progressive aphasia (PPA) have been revised by an international consortium (Gorno-Tempini et al. Neurology 2011;76:1006-14). The aim of this study was to validate the specificity of the new imaging criteria and investigate whether different imaging modalities [magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET)] require different diagnostic subtype-specific imaging criteria. Anatomical likelihood estimation meta-analyses were conducted for PPA subtypes across a large cohort of 396 patients: firstly, across MRI studies for each of the three PPA subtypes followed by conjunction and subtraction analyses to investigate the specificity, and, secondly, by comparing results across MRI vs. FDG-PET studies in semantic dementia and progressive nonfluent aphasia. Semantic dementia showed atrophy in temporal, fusiform, parahippocampal gyri, hippocampus, and amygdala, progressive nonfluent aphasia in left putamen, insula, middle/superior temporal, precentral, and frontal gyri, logopenic progressive aphasia in middle/superior temporal, supramarginal, and dorsal posterior cingulate gyri. Results of the disease-specific meta-analyses across MRI studies were disjunct. Similarly, atrophic and hypometabolic brain networks were regionally dissociated in both semantic dementia and progressive nonfluent aphasia. In conclusion, meta-analyses support the specificity of new diagnostic imaging criteria for PPA and suggest that they should be specified for each imaging modality separately. PMID- 26901361 TI - Predictive Method for Correct Identification of Archaeological Charred Grape Seeds: Support for Advances in Knowledge of Grape Domestication Process. AB - The identification of archaeological charred grape seeds is a difficult task due to the alteration of the morphological seeds shape. In archaeobotanical studies, for the correct discrimination between Vitis vinifera subsp. sylvestris and Vitis vinifera subsp. vinifera grape seeds it is very important to understand the history and origin of the domesticated grapevine. In this work, different carbonisation experiments were carried out using a hearth to reproduce the same burning conditions that occurred in archaeological contexts. In addition, several carbonisation trials on modern wild and cultivated grape seeds were performed using a muffle furnace. For comparison with archaeological materials, modern grape seed samples were obtained using seven different temperatures of carbonisation ranging between 180 and 340oC for 120 min. Analysing the grape seed size and shape by computer vision techniques, and applying the stepwise linear discriminant analysis (LDA) method, discrimination of the wild from the cultivated charred grape seeds was possible. An overall correct classification of 93.3% was achieved. Applying the same statistical procedure to compare modern charred with archaeological grape seeds, found in Sardinia and dating back to the Early Bronze Age (2017-1751 2sigma cal. BC), allowed 75.0% of the cases to be identified as wild grape. The proposed method proved to be a useful and effective procedure in identifying, with high accuracy, the charred grape seeds found in archaeological sites. Moreover, it may be considered valid support for advances in the knowledge and comprehension of viticulture adoption and the grape domestication process. The same methodology may also be successful when applied to other plant remains, and provide important information about the history of domesticated plants. PMID- 26901362 TI - Decreased Level of IgE is Associated with Breast Cancer and Allergic Diseases. AB - BACKGROUND The aim of this study was to explore the prevalence of type I allergic diseases in patients with breast cancer by carrying out a questionnaire survey and IgE detection in a healthy population and in patients with breast cancer. MATERIAL AND METHODS There were 309 patients enrolled and they were further divided into the type I allergic disease group, the newly diagnosed breast cancer with type I allergic disease group, the re-visit breast cancer with type I allergic disease group, and the re-visit breast cancer without type I allergic disease group, as well as a healthy control group. Serum total IgE level was detected by immunoassay. RESULTS The IgE value in the healthy population with type I allergic diseases (89.3+/-51.4 IU/ml) was significantly higher than in those without type I allergic diseases (45.6+/-65.1 IU/ml). There was no significant difference between IgE values in the re-visit breast cancer patients with type I allergic disease (25.1+/-65.1 IU/ml) and those without type I allergic disease (23.0+/-45.9 IU/ml). The area under the ROC curve was 0.618+/ 0.04, sensitivity was 78%, specificity was 47.1%, Youden index was 0.251, and IgE threshold was 32.6 IU/ml. CONCLUSIONS The patients with newly diagnosed breast cancer were susceptible to type I allergic disease at about the same levels as in the healthy population. There was no correlation between breast cancer and type I allergic disease. PMID- 26901364 TI - [Governance of innovative cardiovascular devices: when evidence is not enough]. AB - Aortic stenosis is the most common valve disease and transcatheter aortic valve implantation (TAVI) is considered as an alternative to surgical valve replacement or to medical treatment in inoperable or high-risk patients. Although physicians have learned how to care for critically ill old patients and enable many to survive, major surgical procedures, operating on patients at very high risk, are often not suitable. Studies showed that selected cohorts of patients undergoing TAVI might have better outcomes in terms of survival and quality of life. However, mortality and safety data associated with the less invasive intervention do not always justify such new technologies for all patients with severe aortic stenosis, taking into account also the high cost associated. A systematic review of the available scientific literature has been performed. In this context, a DECIDE framework has been used providing a systematic and transparent approach for going from evidence to healthcare decisions. Before suggesting final recommendations, historical data of interventions done at regional level and regulatory decisions adopted in other countries following health technology assessment analysis, have been analyzed. All final recommendations based on this document have been discussed and reviewed with a working group done by the health operators directly involved in this technology within the regional health service context. Recommendations for the identification of patients suitable for TAVI are given together with a list of characteristics that should be required to all centers eligible for the performance of TAVI and with a procedure able to allow better quality assurance and prospective monitoring process of all new cases enrolled for such intervention. Impact of these recommendations will be measured using a regional registry collecting data on new patients undergoing TAVI. PMID- 26901365 TI - [Facing the unreliability of clinical trials literature]. AB - Journal publications of randomized controlled trials ("literature") have so far formed the basis for evidence of the effects of pharmaceuticals and biologicals. In the last decade, progressively accumulating evidence has shown that literature is affected by reporting bias with evident implications for the reliability of any decision based on literature or its derivatives such as research synthesis. Another important factor is the growing body of evidence of the fragility of editorial quality control mechanisms in biomedicine ande their easy exploitation for marketing purposes in the symbiosis between publishing and the pharmaceutical industry. Regulatory documents are probably more reliable than currently accessible other sources but there are many severe limitations to the long-term use of regulatory documents for research synthesis and decision-making. Instead of trying to reform the fields of research, industry, government, regulation and publishing, I propose basing public health decisions and reimbursement of any important interventions on independent trials and studies following the model pioneered by the Mario Negri Institute of Pharmacological Research. PMID- 26901366 TI - [The criminal liability of the hospital pharmacist vs the liability of the hospital]. AB - This study proposes an analysis of the boundaries of liability of the negligent hospital pharmacist, in relation with the liability of the hospital. The conditions of departure are: the knowledge that the pharmacist works within the limits of compliance programs adopted by the hospital; the finding that, in recent times, there has been an expansion in the objective sense of liability of the pharmacist. The laudable aim of protecting the patient is well accompanied by the violation of the principle of individual criminal liability (Art. 27 of the Constitution) and practical reason for discouraging the risky assets even useful. Through the analysis of the d. lgs. n. 231/2001 regarding the corporate liability for the crime and law n. 158/2012 regarding criminal liability limited to the gross negligence of the health care, it will arrive at the conclusion about the need to recognize a liability for the organization to hospitals, limiting the liability of the hospital pharmacist to cases of chargeability/criminal liability of negligent conduct. PMID- 26901367 TI - [Transcatheter aortic valve implantation: a systematic review of the literature on efficacy and safety data]. AB - BACKGROUND: Aortic stenosis is the most common valve disease and transcatheter aortic valve replacement is considered as an alternative to surgical valve replacement or to medical treatment in inoperable or high-risk patients, but it is not suitable for all patients with severe aortic stenosis, taking into account also the high cost associated. OBJECTIVE: To evaluate the efficacy and safety of transcatheter aortic valve implantation (TAVI) for aortic stenosis via percutaneous, (transfemoral, or endovascular approach) or surgically (transapical, or transventricular) approach. RESULTS: The present review includes 10 randomized controlled trials (RCTs) and 29 observational studies. We combined the outcomes from the individual trials through meta-analysis where possible. We assessed the overall quality of the evidence for the primary outcome using the GRADE system. Regarding TAVI vs. standard surgery, there were no significant differences between TAVI and conventional surgery for mortality at 1 year or more, the frequency of stroke, and heart attack; for mortality at 30 days, no difference was observed in RCTs and the result was in favor of TAVI in observational studies. Another outcome in favor of TAVI was the frequency of major bleeding that was significantly lower in patients treated with TAVI. The quality of the evidence ranged from moderate to very low. Regarding TAVI vs. medical therapy, for the outcome death at 1 year or more, if we consider the RCTs, the results are favorable to TAVI, while in observational studies no significant differences were observed between the two interventions. In contrast, for the outcome mortality at 30 days, in RCTs no significant differences between the two interventions were observed, while the results were favorable to TAVI in observational studies. For the frequency of stroke in the single RCT that reported this outcome, it was significantly lower in patients treated with medical therapy, with no significant differences in the results of observational studies. The results related to the frequency of heart attack from observational studies are in favor of TAVI. The quality of the evidence ranged from low to very low. CONCLUSIONS: Candidates for TAVI are those patients for which conventional open-heart surgery is not recommended because of the risk due to advanced age or important comorbidities. PMID- 26901368 TI - [The clinical pharmacist interventions to improve the immunosuppressive therapy management in a pediatric population: education, adherence, pharmacovigilance]. AB - AIM: To value and improve the adherence to the immunosuppressive therapy in a pediatric population and the pharmacovigilance activity. MATERIALS AND METHODS: From January 2013 to October 2014, the pharmacist has developed an education program for 147 pediatric patients in the management of their home therapy. The methods used to evaluate the adherence were three: the measuring of trough blood concentration of immunosuppressive drugs, a questionnaire and the prescription refill rate. Our secondary goal was to create a family collaboration sensitizing patients and their parents to inform the physician or the pharmacist of any adverse drug reactions. RESULTS: During the education phase, the pharmacist answered patient/family's questions about therapy doubts and curiosities. In the trough blood level monitoring of immunosuppressive drugs, 9% of the patients had an average hematic concentration of immunosuppressive drug out of the expected range. Questionnaires showed that: 12.2% of the patients missed a dose of immunosuppressant drug in the previous month, 2% 2 doses and 1.3% 3 doses. 8.8% of the patients diverged once for about 2 hours the scheduled time in the previous month and 3.4% 2-3 times. 21% of the children/parents said they did not know the correct way of drugs intake in relation to meals. After the training, 45 children/parents followed pharmacist tips more. According the analysis of the prescription refill rate, 10.8% of the patients were late in withdrawing their medications. Through the combination of the three methods, 17.7% of the patients were non-adherent. We identified and reported 15 suspected ADR, of which 4 were serious. CONCLUSION: Children adherence is widely determined by the ability and role of their parents to manage home therapy. On the contrary, teenagers often want to manage their home therapy by themselves. Pharmacist has to talk to the patient to evaluate adherence obstacles and collaborate with the patient in order to overcome them. Parents can have an active role in reporting ADRs to the pharmacist. PMID- 26901370 TI - [Not Available]. PMID- 26901369 TI - [Microbial contamination of surfaces in the departments of Medicine and Surgery: single center prevalence study in Sassari (Italy)]. AB - INTRODUCTION: Healthcare-associated infections (HAIs) represent a clinical and public health problem worldwide. Microbial transmission can frequently occurs between patients or between patients and health-care workers; however, several devices and surfaces could act as reservoir and source of microorganisms. Aim of this cross-sectional study was to show the microbial contamination of devices or surfaces located in the departments of Medicine and Surgery of an Italian University Hospital. METHODS: Swabs were used to sample devices (keyboards, phones) and surfaces (door handles, water closed, light switches), at two different time-points. Samples were then evaluated in the UOC Hygiene and Preventive Medicine laboratory of the same University Hospital. RESULTS: 189 swabs were collected, 95 (53.3%) from the Medicine and 94 (49.7%) from the Surgery Department. The bacterial contamination prevalence was 42.9%, significantly higher in the Medicine than in the Surgery Department (51.6% vs 34%; p=0.015). A greater contamination was observed in water closed (22/36, 61.1%), phones (22/40, 55%), and keyboards of personal computers (18/36, 51.4%; p<0.001). No statistical differences were detected in the contamination rates when the different time-points were compared, as well as in the isolation rate of pathogenic bacterial strains. DISCUSSION: This survey highlights the potential role of devices and surfaces in the HAI pathogenesis. Further longitudinal and analytical studies might better assess the HAI risk associated with bacterial contamination in nosocomial settings. PMID- 26901372 TI - [Not Available]. PMID- 26901373 TI - Good quality blastocyst from non-/mono-pronuclear zygote may be used for transfer during IVF. AB - Although healthy infants have developed from non- and mono-pronuclear zygotes, the transfer of embryos from non- and mono-pronuclear zygotes is not recommended because there are no proper selection criteria. In the present study, we discuss how to select non- and mono-pronuclear embryos with the highest developmental potential at 19-20 hours post-insemination. We found that the percentage of blastocysts with normal chromosome constitution in non-pronuclear zygotes was slightly higher than in mono-pronuclear zygotes. Non- and mono-pronuclear embryos that were at the 4-cell stage on D2 and/or at the 6- to 8-cell stage on D3 had higher incidence rates of blastocysts with normal chromosome constitutions. We also found higher incidences of blastocysts with normal chromosome constitution on D6 than on D5. The results suggest that if high quality non- and mono pronuclear zygotes develop to the 4-cell stage on D2 and the 6-to 8- cell stages on D3, along with high quality D6 blastocysts, the incidence of blastocysts with normal chromosome constitution is higher. PMID- 26901374 TI - Balancing Effort and Information Transmission During Language Acquisition: Evidence From Word Order and Case Marking. AB - Across languages of the world, some grammatical patterns have been argued to be more common than expected by chance. These are sometimes referred to as (statistical) language universals. One such universal is the correlation between constituent order freedom and the presence of a case system in a language. Here, we explore whether this correlation can be explained by a bias to balance production effort and informativity of cues to grammatical function. Two groups of learners were presented with miniature artificial languages containing optional case marking and either flexible or fixed constituent order. Learners of the flexible order language used case marking significantly more often. This result parallels the typological correlation between constituent order flexibility and the presence of case marking in a language and provides a possible explanation for the historical development of Old English to Modern English, from flexible constituent order with case marking to relatively fixed order without case marking. In addition, learners of the flexible order language conditioned case marking on constituent order, using more case marking with the cross-linguistically less frequent order, again mirroring typological data. These results suggest that some cross-linguistic generalizations originate in functionally motivated biases operating during language learning. PMID- 26901375 TI - Improving the safety of vaccine delivery. AB - Vaccines save millions of lives per annum as an integral part of community primary care provision worldwide. Adverse events due to the vaccine delivery process outnumber those arising from the pharmacological properties of the vaccines themselves. Whilst one in three patients receiving a vaccine will encounter some form of error, little is known about their underlying causes and how to mitigate them in practice. Patient safety incident reporting systems and adverse drug event surveillance offer a rich opportunity for understanding the underlying causes of those errors. Reducing harm relies on the identification and implementation of changes to improve vaccine safety at multiple levels: from patient interventions through to organizational actions at local, national and international levels. Here we highlight the potential for maximizing learning from patient safety incident reports to improve the quality and safety of vaccine delivery. PMID- 26901376 TI - Moving toward appropriateness of breast cancer care: a balanced act to redefine the scope of standard of care. PMID- 26901377 TI - Common invasive fungal diseases: an overview of invasive candidiasis, aspergillosis, cryptococcosis, and Pneumocystis pneumonia. AB - Every year, Candida, Aspergillus, Cryptococcus and Pneumocystis infect an estimated two million individuals worldwide. Most are immunocompromised or critically ill. Candida is the most common fungal pathogen of the critically ill and of recipients of transplanted abdominal organs. In high-risk haemato oncological patients, in contrast, the introduction of antifungal prophylaxis with fluconazole and later with mould-active posaconazole has led to a remarkable reduction of invasive candidiasis and is likely to have a similar effect on invasive aspergillosis. Invasive aspergillosis remains the dominant invasive fungal disease (IFD) of haemato-oncological patients and solid-organ transplant recipients and is increasingly found in individuals with exacerbated chronic obstructive pulmonary disease on corticosteroids. In the developed world, owing to antiretroviral therapy Pneumocystis pneumonia and cryptococcosis have become rare in patients with human immunodeficiency virus (HIV) and are mainly found in solid-organ transplant recipients or immunocompromised patients. In the developing world, cryptococcosis remains a common and highly lethal disease of HIV positive individuals. With invasive candidiasis and invasive aspergillosis, timely diagnosis is the principal challenge. The clinical presentation is nonspecific and current diagnostic tests lack sensitivity and specificity. The combination of several tests improves sensitivity, but not specificity. Standardised polymerase chain-reaction-based assays may be promising tools for more rapid and specific diagnosis of candidiasis and invasive aspergillosis. Nevertheless, initiation of treatment is often based solely on clinical suspicion. Empirical therapy, however, may lead to over-treatment of patients without IFD or it may miss its target in the case of resistance. Despite the success of antifungal prophylaxis in reducing the incidence of IFDs in haemato oncological patients, there are a considerable number of breakthrough infections demonstrating not only fungal resistance but also the emergence of rare and often lethal fungal pathogens. Knowledge of the local epidemiology and antifungal resistance is therefore pivotal. Current trial-based guidelines leave major gaps in identifying those most at risk, who may benefit from prophylaxis. Ongoing searches for disease-associated genetic polymorphisms may contribute to the establishment of individual risk profiles and targeted prophylaxis. PMID- 26901378 TI - Concentrations of adipokines in children before and after hematopoietic stem cell transplantation. AB - Adipokines have multiple effects, including regulation of glucose metabolism, cell proliferation, inflammation, and angiogenesis. The aim of the study was to determine plasma concentrations of adiponectin, apelin, leptin, and resistin as well as soluble leptin receptor in pediatric hematopoietic stem cell transplantation (HSCT). The expression of genes encoding the studied peptides was measured using microarray technique. Plasma concentrations of tested peptides were measured before and after oral glucose tolerance test in children treated with HSCT (n = 38) and in healthy controls (n = 26). The peptides were measured before HSCT (pre-HSCT group; n = 38) and after a median of 6 months after HSCT (post-HSCT group; n = 27 of 38 children treated with HSCT). In addition, measurements of fasting plasma glucose, insulin, lipids, and high-sensitivity C reactive protein (hsCRP) were performed. In both HSCT groups, atherogenic lipid profile, low-grade systemic inflammation was observed. Leptin, adiponectin, and resistin also appear to be good markers of disease burden and low-grade systemic inflammation. Adipokines may be good markers of disease burden and may influence metabolic complications of HSCT. Future studies on larger groups of patients will explain if changes of the concentrations of leptin, adiponectin, and apelin observed in our study and confirmed by expression levels influence engraftment and reconstitution of cell lines. PMID- 26901380 TI - Chemically prepared La2Se3 nanocubes thin film for supercapacitor application. AB - Lanthanum selenide (La2Se3) nanocubes thin film is prepared via successive ionic layer adsorption and reaction (SILAR) method and utilized for energy storage application. The prepared La2Se3 thin film is characterized by X-ray diffraction, field emission scanning electron microscopy and contact angle measurement techniques for structural, surface morphological and wettability studies, respectively. Energy dispersive X-ray microanalysis (EDAX) is performed in order to obtain the elemental composition of the thin film. The La2Se3 film electrode shows a maximum specific capacitance of 363 F g(-1) in a 0.8 M LiClO4/PC electrolyte at a scan rate of 5 mV s(-1) within 1.3 V/SCE potential range. The specific capacitive retention of 83 % of La2Se3 film electrode is obtained over 1000 cyclic voltammetry cycles. The predominant performance, such as high energy (80 Wh kg(-1)) and power density (2.5 kW kg(-1)), indicates that La2Se3 film electrode facilitates fast ion diffusion during redox processes. PMID- 26901379 TI - The impact of retinol loading and surface charge on the hepatic delivery of lipid nanoparticles. AB - The present work developed lipid nanoparticles to determine whether retinol loading and surface charge influenced liver targeting and biodistribution. Silibinin for treating liver fibrosis was used as the active model. The capability of nanoparticles to suppress hepatic stellate cells (HSCs) was investigated by examining cell viability and alpha-smooth muscle actin (alpha SMA). The biodistribution of the nanocarriers in rats was monitored by real-time and organ bioimaging after an intravenous injection. Silibinin concentration in the organs was detected as well. Anionic nanoparticles showed a mean size of around 260 nm, which was greater than that of cationic nanoparticles (about 170 nm). The encapsulation percentage of silibinin was >98% for both anionic and cationic nanoparticles. All nanoparticles tested were able to be ingested into HSCs, with no difference between the formulations. The positive nanoparticles produced activated HSC apoptosis much more strongly than negative nanoparticles. The alpha-SMA suppression exhibited a contrary trend. The nanoparticles rapidly accumulated in the liver and spleen. Retinol incorporation in nanoparticles offers an active targeting approach to the liver via retinol binding protein (RBP). The negatively charged formulation containing retinol achieved higher uptake and longer retention in the liver than the other formulations. Silibinin inclusion in nanoparticles significantly decreased lung deposition and increased liver uptake. The lipid nanosystems promoted silibinin distribution to the liver by 2-3-fold compared to the free control. A better liver-specific selectivity was obtained by retinol-loaded anionic nanocarriers. It is important to optimize the formulations of the lipid nanoparticles for maximizing hepatic targeting. PMID- 26901381 TI - Fraxinus pollen and allergen concentrations in Ourense (South-western Europe). AB - In temperate zones of North-Central Europe the sensitization to ash pollen is a recognized problem, also extended to the Northern areas of the Mediterranean basin. Some observations in Switzerland suggest that ash pollen season could be as important as birch pollen period. The allergenic significance of this pollen has been poorly studied in Southern Europe as the amounts of ash pollen are low. Due to the high degree of family relationship with the olive pollen major allergen (backed by a sequence identity of 88%), the Fraxinus pollen could be a significant cause of early respiratory allergy in sensitized people to olive pollen as consequence of cross-reactivity processes. Ash tree flowers in the Northwestern Spain during the winter months. The atmospheric presence of Ole e 1 like proteins (which could be related with the Fra a 1 presence) can be accurately detected using Ole e 1 antibodies. The correlation analysis showed high Spearman correlation coefficients between pollen content and rainfall (R(2)= 0.333, p<0.01) or allergen concentration and maximum temperature (R(2)=-0.271, p<0.01). In addiction CCA analysis showed not significant differences (p<0.05) between the component 1 and 2 variables. PCFA analysis plots showed that the allergen concentrations are related to the presence of the Fraxinus pollen in the air, facilitating the wind speed its submicronic allergen proteins dispersion. In order to forecast the Fraxinus allergy risk periods, two regression equations were developed with Adjusted R(2) values around 0.48-0.49. The t-test for dependent samples shows no significant differences between the observed data and the estimated by the equations. The combination of the airborne pollen content and the allergen quantification must be assessed in the epidemiologic study of allergic respiratory diseases. PMID- 26901383 TI - Fatigue- and training-related changes in 'beta' intermuscular interactions between agonist muscles. AB - The synchronous activation of the muscles involved in force production is crucial for the neuromuscular performance, but the underlying mechanisms remain to be fully elucidated. Our aim was thus to contribute to understand the mechanisms involved in the synergistic activation of agonist muscles. Through wavelet-based time-frequency analysis, this study investigated the modulation of 'beta' intermuscular interactions (IM) during maximum isometric knee extensions performed before and after repetitive submaximal fatiguing contractions. Three groups of participants were included: 9 untrained subjects (control group, CO), 10 elite rugby league players (strength-trained group, ST) and 7 trail runners (endurance-trained group, ED), engaged for 5+ years in intense strength and endurance training, respectively. Before fatigue, CO showed higher IM when compared to ED, and a trend to higher IM when compared to ST. Following fatiguing contractions, all groups showed a decline in neuromuscular performance concomitant with a change (decline) in IM values for CO only. No differences were found between ST and ED regarding to IM either before or after fatiguing contractions. These findings suggested both a form of optimization of intermuscular coupling in trained individuals and the functional importance of intermuscular coupling as a mechanism responsible for the maintenance of the neuromuscular performance. PMID- 26901382 TI - Patterns and Associated Factors of Physical Activity among Adolescents in Nigeria. AB - INTRODUCTION: Understanding the context where adolescents' physical activity (PA) takes place could impact a more targeted approach to implement PA promotion and interventions in Africa. However, standardized data on adolescents' PA behaviour is lacking in Nigeria. We described PA patterns in the various domains (home, school, transport, leisure-time) and intensity categories (light-intensity PA, moderate- to vigorous- intensity physical activity [MVPA] and total PA), and their associations with sociodemographic factors and socioeconomic status (SES) among secondary school adolescents in Nigeria. METHODS: A cross-sectional survey was conducted in a representative sample of 1006 secondary school adolescents (12 18 years, 50.4% girls) in Maiduguri, Nigeria. Self-reported PA was assessed with an adapted version of the Activity Questionnaire for Adolescents and Young Adults. Outcomes were weekly minutes (min/wk) of PA spent in the various domains and intensity categories. Multivariate ANOVA was used to examine associations of PA scores (domains and intensity levels) with adolescents' sociodemographic characteristics and SES, and track differences in PA scores between subgroups. RESULTS: The total sample reported most PA at school (1525 min/wk), the least during active transportation (210 min/wk), and only 37% engaged in 60 min of MVPA daily. Boys reported significantly more leisure-time PA (P<0.001), active transportation (P<0.001), MVPA (P = 0.023) and total PA (P = 0.003) than girls, while girls reported more school-based PA (P = 0.009), home-based PA (P<0.001) and light-intensity PA (P<0.001) than boys. Moderate-intensity PA (P = 0.024) and total PA (P = 0.049) were significantly higher in younger age group than in older group. Household car ownership was associated with less active transportation (P = 0.009), less moderate-intensity PA (P = 0.048) and with more leisure-time PA (P = 0.013). High parental SES was associated with more leisure-time PA (P = 0.002), more MVPA (P = 0.047) and less active transportation (P<0.001). Adolescents of various weight status differed significantly in their leisure-time PA (P<0.001), moderate-intensity PA (P = 0.011) and total PA (P = 0.033). CONCLUSIONS: The patterns and levels of physical activity among adolescents in Nigeria vary according to the adolescents' age, gender, weight status and SES. These findings have important public health implications for identifying subgroups of Nigerian adolescents that should be targeted for effective physical activity promoting interventions. PMID- 26901384 TI - Deregulated hepatic microRNAs underlie the association between non-alcoholic fatty liver disease and coronary artery disease. AB - BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) appears to be a new risk factor for the development of coronary artery disease (CAD). Members of a class of non-coding RNAs, termed microRNAs (miRNAs), have been identified as post transcriptional regulators of cholesterol homoeostasis and can contribute to the development of NAFLD. The aims of this study were to (i) to assess the relationship between NAFLD and sudden cardiac death (SCD) from severe CAD in forensic autopsies and (ii) to quantify several hepatic miRNAs previously associated with lipid metabolism and NAFLD to correlate their expression with the presence of NAFLD, CAD, obesity parameters and postmortem lipid profile. METHODS: A total of 133 cases of autopsies with SCD and established CAD (patient group, CAD-SCD) and 106 cases of non-CAD sudden death (control group, non-CAD-SD) were included. miRNAs were quantified in frozen liver tissues. RESULTS: Males predominated in both groups. Patients more frequently exhibited NAFLD and necroinflammatory steatohepatitis (NASH) than controls (62% vs 26%, P = 0.001 and 42% vs 26%, P = 0.001 respectively). In both groups, the presence of NAFLD correlated with body mass index and abdominal circumference (P < 0.05). An increase in miR-34a-5p and a decrease in miR-122-5p and -29c-3p in patients with NASH vs controls without NAFLD were observed (P < 0.05). Finally, significant correlations between miR-122-5p and unfavourable lipid profile and also hs-CRP and miR-34a-5p were noted. CONCLUSIONS: CAD is associated with NAFLD and NASH. The hepatic miRNAs studied appear to be associated with NAFLD severity and may promote CAD through lipid metabolism alteration and/or promotion of the systemic inflammation. PMID- 26901385 TI - Does SOD3 R213G Homozygosity Influence Morbidity, Mortality, and Lung Function in the General Population? AB - The extracellular superoxide dismutase (SOD3, EC-SOD) enzyme is a major extracellular scavenger of the superoxide anion, a free radical with the potential to cause oxidative damage. Previously, R213G heterozygosity has been associated with a decreased risk of chronic obstructive pulmonary disease (COPD) and an increased risk of ischemic heart disease (IHD). We questioned whether SOD3 R213G homozygosity (213GG) influences morbidity, mortality, and lung function. We found 14 R213G homozygotes (213GG) among 95,871 individuals (1/7000) from the Copenhagen General Population Study and the Copenhagen City Heart Study. The hazard ratio for homozygotes versus noncarriers (NC) (213RR) was 2.8 (95% confidence interval: 1.2-6.8, p = 0.02) for IHD, 1.8 (0.7-4.8, p = 0.25) for any form of cancer, and 2.3 (0.9-6.2, p = 0.10) for all-cause mortality. R213G heterozygosity was not associated with morbidity or mortality. Among never smokers, we found a 20% lower forced expiratory volume in 1 s (FEV1)% predicted (p = 0.003), a 16% lower FVC% predicted (p = 0.01), and a 7% lower FEV1/FVC ratio (p = 0.02) in R213G homozygotes compared to NC. Our results lead to the hypotheses that the SOD3 enzyme plays a role in cardiovascular disease and in impairing and maintaining lung function in never-smokers. However, our findings should be retested in larger studies and in nonsmoking COPD patient cohorts. Antioxid. Redox Signal. 24, 884-891. PMID- 26901386 TI - A Prospective, Descriptive Study to Determine the Rate and Characteristics of and Risk Factors for the Development of Medical Device-related Pressure Ulcers in Intensive Care Units. AB - Pressure ulcers do not develop only in areas with bony prominences; they can develop in any tissue under pressure, including pressure exerted by medical devices. A prospective, descriptive study was conducted from December 15, 2013 to March 25, 2014 to determine the prevalence, risk factors, and characteristics of medical device-related hospitalacquired pressure ulcers (MDR HAPUs) among all patients (N = 175) in 5 adult intensive care units (ICUs) in a university hospital in Turkey. The previously established point prevalence of hospital acquired pressure ulcers (HAPUs) in these ICUs was 15%. Patients were evaluated in the first 24 hours after admission and observed 6 times thereafter in intervals of 48 hours. Demographic (eg, age, gender, body mass index) and medical device-related pressure ulcer data (eg, location, device type, stage), and Braden Scale scores were collected and analyzed; frequencies and percentages were calculated and Mann-Whitney U Test, t-test, and odds ratios were applied. Twenty seven (27) patients (15.4%) developed nonMDR HAPUs and 70 (40.0%) developed MDR HAPUs. MDR HAPUs occurred most frequently (45.0%) in patients with an endotracheal tube. The most frequent type (42.6%) was Stage II. The highest rates of MDR HAPUs were observed among internal medicine ICU patients (OR 7.041), patients who also had a nonMDR HAPU (OR 6.6), patients in the high Braden risk score group (OR 1.8), or patients who received enteral feeding (OR 2.12). Because of the high rate of MDR HAPUs noted, policies and procedures aimed at preventing medical device-related pressure ulcers are needed. PMID- 26901387 TI - Critical Evaluation of the Jackson/Cubbin Pressure Ulcer Risk Scale - A Secondary Analysis of a Retrospective Cohort Study Population of Intensive Care Patients. AB - Although the Jackson/Cubbin pressure ulcer (PU) risk scale performs best among risk scales used in intensive care units (ICUs), its performance was not fully satisfactory. In 2010, a minimally modified Jackson/Cubbin (mJ/C) PU risk scale was introduced to formalize PU risk assessment in a large medical-surgical ICU in Finland. The purpose of this secondary analysis was to examine whether individual categories of the mJ/C scale have similar weight and whether the scores within each category (from 1 to 4; 1 equaling highest risk and 4 equaling lowest risk) are linear, as is assumed for the original and modified scales. Using data from a cohort of 1,616 consecutively admitted patients retrieved from the ICU database, a detailed secondary analysis of each of the 12 main scoring categories of the Jackson/Cubbin risk scale was performed using logistic regression and analysis of linearity and weight. Of the 1,616 admitted patients, 168 developed a PU during their ICU stay. Among the risk categories, body mass index, nutrition, respiration, age, and transportation during the 48 hours before scoring did not contribute significantly (P >0.05) to the total risk score or the actual development of a PU. The 7 other main categories - incontinence, mobility, medical history, oxygen requirement, need for assistance with hygiene, hemodynamics, and general skin condition - were the main risk contributors. Although only the linearity of the different categories correlated significantly with the predictive value of the categories, the linearity as well as the weights of the categories were at variance from what was assumed originally. The mJ/C scale needs refinement to be a more accurate instrument for PU risk assessment of ICU patients. Not all mJ/C categories were found to contribute to the risk and, when they do, their weight and linearity vary from what has been assumed. The categories respiration and oxygen requirement and the categories mental condition, mobility, and hygiene may overlap. The importance of the incontinence category depends on the frequency of urinary and fecal incontinence management system usage. A simpler, more valid and more sensitive risk assessment scale than the current Jackson/Cubbin scale is needed for ICU patients. PMID- 26901388 TI - Turkish Nurses' Opinions of the Braden and Waterlow Pressure Ulcer Risk Assessment Scales: A Descriptive Pilot Study. AB - Risk evaluation scales are used as part of prevention strategies for pressure ulcers (PUs). Two of the more used scales, the Braden and Waterlow Pressure Ulcer Risk Assessment Scales (B-PURAS and W-PURAS, respectively) are used in Turkey and worldwide, and their validity in terms of sensitivity, specificity, and predictive validity have been examined in various studies. To determine nurses' opinions of B-PURAS and W-PURAS in terms of administration time, practicality, clarity, and perceived ability to encompass PU risks and accurately predict PUs, a descriptive study was conducted from October 15, 2011 to November 20, 2011 at a university hospital among nurses who volunteered to participate. Demographic information collected and assessed included age, highest degree of education completed, and practice area. Participants were trained to use both scales by researchers during a 1-hour session and asked to use them for 2 weeks in their daily practice. The nurses then completed a paper-and-pencil, 12-item questionnaire measuring agreement with general questions about PURAS with options to provide comments. In addition, the questionnaire contained 3 openended questions on scale preference, 1 question to rate perceived scale accuracy in predicting PUs, and the opportunity to recommend changes to the scales. Data were analyzed using SPSS 20.0. Frequencies, percentages, and Spearman's rank correlations were calculated. Eighty-three (83) registered nurses (mean age 27.46 +/- 3.73, mean nursing experience 6.53 +/- 3.25 [range 0.5-16] years) participated; 18.1% of the nurses had prior experience using such scales, and none of the clinics in the study facility had used PU risk scales previously. Most participants (71, 85.5%) had a bachelor's degree, 62 (74.7%) worked in a facility that admitted patients at high risk for developing PU, but 66 (almost 80%) saw fewer than 4 ulcers per week. Each nurse performed an average of 22 assessments during the study for a total of 1,826 assessments. Participants generally found both scales practical and appropriate; almost 75% thought the B PURAS was acceptable for use in all clinics, compared to 51% for the W-PURAS; only 20 participants questioned the scales' accuracy in predicting PUs. While 43% preferred the B-PURAS for precision, clarity, and practicability, 25% preferred the W-PURAS because it was more comprehensive. Also, the older the nurse, the more likely the preference for the B-PURAS (P less than 0.019). Some nurses (13%) suggested adding different risk factors such as serum albumin. Overall, 61.4% stated they would prefer to use the B-PURAS over the W-PURAS. Nurses' recommendations should be considered for practice and new scale development and testing, ideally in different patient populations. PMID- 26901389 TI - Cardiac troponins and volatile anaesthetics in coronary artery bypass graft surgery: A systematic review, meta-analysis and trial sequential analysis. AB - BACKGROUND: Reports from animal studies indicate that volatile anaesthetics protect the myocardium against the effects of acute ischaemia-reperfusion injury by reducing infarct size. This cardioprotective effect in the clinical setting of coronary artery bypass graft (CABG) surgery, where the heart is subjected to global ischaemia-reperfusion injury, remains controversial. OBJECTIVE: The objective was to demonstrate that clinical studies investigating the cardioprotective effect of volatile anaesthetics on cardiac troponins in CABG are no longer warranted. We also investigated the effect of volatile anaesthetics on cardiac enzymes in off-pump cardiac surgery. DESIGN: Systematic review of randomised clinical trials, meta-analyses and trial sequential analysis (TSA). DATA SOURCES: Trials between January 1985 and March 2015 were obtained from electronic databases (Medline, Excerpta Medica Database (EMBASE), Cochrane Controlled Trial Register, abstracts from major anaesthesiology and cardiology journals and reference lists of relevant randomised trials and review articles. ELIGIBILITY CRITERIA: Relevant randomised clinical trials were included. We investigated the effect of volatile anaesthetics in both off-pump and on-pump CABG surgery with respect to troponin release [peak postoperative cardiac troponin I (cTnI) and cardiac troponin T (cTnT), cTnI/cTnT] and performed two separate meta-analyses. TSA was used to overcome the weakness of a type-1 error associated with repeated meta-analyses. RESULTS: From 30 studies, 2578 patients were pooled for the meta-analysis. The outcome significantly favours the use of peroperative volatile over non-volatile anaesthetics during on-pump CABG surgery with regard to peak postoperative cTnI (0.995 mg l; standard mean difference, 95% confidence interval, -1.316 to -0.673; P < 0.001). Meta-analysis of 11 off-pump studies showed no difference in peak postoperative cTnI (0.385 mg l; standard mean difference, 95% confidence interval, -0.857 to 0.087; P = 0.11). TSA indicated that the required information size for on-pump surgery was 1072 patients, and for off-pump surgery it was 1442; this latter figure has not yet been reached. CONCLUSION: Studies investigating the cardioprotective effect of volatile anaesthetics on cardiac troponins in on-pump CABG surgery are no longer warranted. This is not yet the case for off-pump surgery. PMID- 26901390 TI - Morbidity and mortality of vulvar and vaginal cancers: Impact of 2-, 4-, and 9 valent HPV vaccines. AB - Vaginal and vulvar cancers do not account for a large proportion of gynecologic malignancies but their impact is significant. Both vaginal and vulvar lesions have precursors and display levels of dysplasia before progression to invasive disease. Human Papillomavirus (HPV) is a known causative agent of such dysplasia and can be detected now more readily than ever with adequate recognition techniques and provider awareness. Although HPV vaccination is still lagging compared to other recommended childhood vaccinations, the impact on lower genital tract neoplasia is promising. The bivalent and quadrivalent vaccines have been shown to be efficacious and the newest nonavalent vaccine should add even more of impact on coverage of cancer-causing HPV types. Although it is still early to show true clinical and population-based disease reduction due to low disease incidence and relatively short time of vaccine availability, the potential is noteworthy. PMID- 26901391 TI - Food web effects of titanium dioxide nanoparticles in an outdoor freshwater mesocosm experiment. AB - Over the course of 78 days, nine outdoor mesocosms, each with 1350 L capacity, were situated on a pontoon platform in the middle of a lake and exposed to 0 MUg L(-1) TiO2, 25 MUg L(-1) TiO2 or 250 MUg L(-1) TiO2 nanoparticles in the form of E171 TiO2 human food additive five times a week. Mesocosms were inoculated with sediment, phytoplankton, zooplankton, macroinvertebrates, macrophytes and fish before exposure, ensuring a complete food web. Physicochemical parameters of the water, nutrient concentrations, and biomass of the taxa were monitored. Concentrations of 25 MUg L(-1) TiO2 and 250 MUg L(-1) TiO2 caused a reduction in available soluble reactive phosphorus in the mesocosms by 15 and 23%, respectively, but not in the amount of total phosphorus. The biomass of Rotifera was significantly reduced by 32 and 57% in the TiO2 25 MUg L(-1) and TiO2 250 MUg L(-1) treatments, respectively, when compared to the control; however, the biomass of the other monitored groups-Cladocera, Copepoda, phytoplankton, macrophytes, chironomids and fish-remained unaffected. In conclusion, environmentally relevant concentrations of TiO2 nanoparticles may negatively affect certain parameters and taxa of the freshwater lentic aquatic ecosystem. However, these negative effects are not significant enough to affect the overall function of the ecosystem, as there were no cascade effects leading to a major change in its trophic state or primary production. PMID- 26901392 TI - 24-hour work shifts, sedentary work, and obesity in male firefighters. AB - BACKGROUND: Little is known about the occupational risk factors for obesity in US firefighters. METHODS: 308 male California firefighters, who participated in a work and obesity project, were chosen. Working conditions were measured with a firefighter-specific occupational health questionnaire. Adiposity was clinically assessed using body mass index (BMI), waist circumference (WC), and body fat percent. RESULTS: In a multivariate analysis, the prevalence of obesity by all measures was significantly higher (PRs = 3.69-6.03, P < 0.05) in the firefighters who reported seventeen to twenty-one shifts than those who reported eight to eleven shifts in the past month. Prolonged sedentary work was also a risk factor for obesity by BMI (PR = 4.18, P < 0.05). Furthermore, there was a linear dose response relationship of obesity by BMI and WC with the number of 24-hr shifts and sedentary work. CONCLUSIONS: Many additional 24-hr shifts and prolonged sedentary work substantially increased the risk for obesity in male firefighters. Am. J. Ind. Med. 59:486-500, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26901394 TI - Predictors of perceived benefits and drawbacks of using paid service among daughter and daughter-in-law caregivers of people with dementia. AB - This study examines the types of benefits and drawbacks of a sample of daughter and daughter-in-law caregivers (CG) of people with dementia and explores the predictors associated with the identified benefits and drawbacks. The current study used a secondary analysis of a purposive sample of 102 daughters or daughters-in-law living in Northeast Ohio who were required to be using at least 8 hours of paid services per week to help in caring for their care recipient (CR) with Alzheimer's disease or other memory problems. Logistic regression was used. All respondents answered that there were benefits of having the paid help, but 51% of them reported drawbacks as well. The analyses revealed that predictors of each identified benefit and drawback were different. Information about benefits and drawbacks of paid help is useful for service providers to design better services for CGs of people with dementia. PMID- 26901393 TI - Ex Vivo and In Vivo Imaging and Biodistribution of Aptamers Targeting the Human Matrix MetalloProtease-9 in Melanomas. AB - The human Matrix MetalloProtease-9 (hMMP-9) is overexpressed in tumors where it promotes the release of cancer cells thus contributing to tumor metastasis. We raised aptamers against hMMP-9, which constitutes a validated marker of malignant tumors, in order to design probes for imaging tumors in human beings. A chemically modified RNA aptamer (F3B), fully resistant to nucleases was previously described. This compound was subsequently used for the preparation of F3B-Cy5, F3B-S-acetylmercaptoacetyltriglycine (MAG) and F3B-DOTA. The binding properties of these derivatives were determined by surface plasmon resonance and electrophoretic mobility shift assay. Optical fluorescence imaging confirmed the binding to hMMP-9 in A375 melanoma bearing mice. Quantitative biodistribution studies were performed at 30 min, 1h and 2 h post injection of 99mTc-MAG-aptamer and 111In-DOTA-F3B. 99mTc radiolabeled aptamer specifically detected hMMP-9 in A375 melanoma tumors but accumulation in digestive tract was very high. Following i.v. injection of 111In-DOTA-F3B, high level of radioactivity was observed in kidneys and bladder but digestive tract uptake was very limited. Tumor uptake was significantly (student t test, p<0.05) higher for 111In-DOTA-F3B with 2.0%ID/g than for the 111In-DOTA-control oligonucleotide (0.7%ID/g) with tumor to muscle ratio of 4.0. Such difference in tumor accumulation has been confirmed by ex vivo scintigraphic images performed at 1h post injection and by autoradiography, which revealed the overexpression of hMMP-9 in sections of human melanomas. These results demonstrate that F3B aptamer is of interest for detecting hMMP-9 in melanoma tumor. PMID- 26901395 TI - Spin State Energetics and Oxyl Character of Mn-Oxo Porphyrins by Multiconfigurational ab Initio Calculations: Implications on Reactivity. AB - Important electromeric states in manganese-oxo porphyrins MnO(P)(+) and MnO(PF4)(+) (porphyrinato or meso-tetrafluoroporphyrinato) have been investigated with correlated ab initio methods (CASPT2, RASPT2), focusing on their possible role in multistate reactivity patterns in oxygen transfer (OAT) reactions. Due to the lack of oxyl character, the Mn(V) singlet ground state is kinetically inert. OAT reactions should therefore rather proceed through thermally accessible triplet and quintet states that have a more pronounced oxyl character. Two states have been identified as possible candidates: a Mn(V) triplet state and a Mn(IV)O(L(*)a2u)(+) quintet state. The latter state is high-lying in MnO(P)(+) but is stabilized by the substitutions of H by F at the meso carbons (where the a2u orbital has a significant amplitude). Oxyl character and Mn-O bond weakening in these two states stems from the fact that the Mn-O pi* orbitals become singly (triplet) or doubly occupied (quintet). Moreover, an important role for the reactivity of the triplet state is also likely to be played by the pi bond that has an empty pi* orbital, because of the manifest diradical character of this pi bond, revealed by the CASSCF wave function. Interestingly, the diradical character of this bond increases when the Mn-O bond is stretched, while the singly occupied pi* orbital looses its oxygen radical contribution. The RASPT2 results were also used as a benchmark for the description of excited state energetics and Mn-O oxyl character with a wide range of pure and hybrid density functionals. With the latter functionals both the Mn(V) -> Mn(IV) promotion energy and the diradical character of the pi bond (with empty pi*) are found to be extremely dependent on the contribution of exact exchange. For this reason, pure functionals are to be preferred. PMID- 26901396 TI - Interaction Mechanism of Oil-in-Water Emulsions with Asphaltenes Determined Using Droplet Probe AFM. AB - Emulsions with interface-active components at the oil/water interface have long been of fundamental and practical interest in many fields. In this work, the interaction forces between two oil droplets in water in the absence/presence of asphaltenes were directly measured using droplet probe atomic force microscopy (AFM) and analyzed using a theoretical model based on Reynolds lubrication theory and the augmented Young-Laplace equation by including the effects of disjoining pressure. It was revealed that the interaction forces measured between two pristine oil droplets (i.e., toluene) could be well described by the classical Derjaguin-Landau-Verwey-Overbeek (DLVO) theory, while an additional steric interaction should be included in the presence of asphaltenes in the oil. The surface interaction and the stability of oil droplets in aqueous solution were demonstrated to be significantly influenced by the asphaltenes concentration in oil, salt concentration, pH, and presence of divalent ions (Ca(2+)) in water. Adsorbed asphaltenes at the oil/water interface led to more negative surface potential of the oil/water interface and also induced steric repulsion between oil droplets, inhibiting the drop coalescence and stabilizing the oil-in-water emulsion. Lower pH of aqueous solution could lead to less negative surface potential and weaken the repulsion between oil droplets. Addition of divalent ions (Ca(2+)) was found to disrupt the protecting effects of adsorbed asphaltenes at oil/water interface and induce coalescence of oil droplets. Our results provide a useful methodology for quantifying the interaction forces and investigating the properties of asphaltenes at the oil/water interfaces and provide insights into the stabilization mechanism of oil-in-water emulsions due to asphaltenes in oil production and water treatment. PMID- 26901397 TI - A 3D Homochiral MOF [Cd2(d-cam)3]*2Hdma*4dma for HPLC Chromatographic Enantioseparation. AB - Up to now, some chiral metal-organic frameworks (MOFs) have been reported for enantioseparation in liquid chromatography. Here we report a homochiral MOF, [Cd2(d-cam)3].2Hdma.4dma, used as a new chiral stationary phase for high performance liquid chromatographic enantioseparation. Nine racemates of alcohol, naphthol, ketone, and base compounds were used as analytes for evaluating the separation properties of the chiral MOF packed column. Moreover, some effects such as mobile phase composition, column temperature, and analytes mass for separations on this chiral column also were investigated. The relative standard deviations for the resolution values of run-to-run and column-to-column were less than 2.1% and 3.2%, respectively. The experimental results indicate that the homochiral MOF offered good recognition ability, which promotes the application of chiral MOFs use as stationary phase for enantioseparation. PMID- 26901399 TI - Beyond MBRRACE: new developments to stem the tide of postpartum haemorrhage. PMID- 26901398 TI - Compliance with National Institute of Health and Care Excellence risk-based screening for Gestational Diabetes Mellitus in nulliparous women. AB - OBJECTIVE: To investigate compliance with risk-based screening for Gestational Diabetes Mellitus (GDM) in a nulliparous cohort. DESIGN: A retrospective analysis of nulliparous women recruited to a prospective cohort, the Screening for Pregnancy Endpoints (SCOPE) study, was performed. Population included 2428 healthy nulliparous women with singleton pregnancies, recruited within Cork, Ireland; and Manchester, Leeds and London, United Kingdom. Compliance with risk factor screening for GDM was assessed in relation to the following risk factors: obesity, family history of diabetes and increased ethnic risk. GDM was diagnosed using an oral Glucose Tolerance Test (GTT) with locally employed diagnostic criteria. Statistical analysis was performed using Statistical Packages for Social Sciences (SPSS V22). Descriptive statistics are presented for the various baseline characteristics using numbers and percentages. Cross tabulation was used to compare relevant groups. When comparing group distributions Chi-square test was used. p-value <0.05 was considered statistically significant. RESULTS: In the entire cohort of 2432 women, 27% (650 Women) had one or more identifiable risk factors as defined by National Institute of Health and Care Excellence (NICE) for GDM. Of those that had identifiable GDM risk factors according to the NICE guidelines, 395(60.8%) were appropriately screened. 253 (38.9%) had risk factors but were not screened. 261 (14.6%) had no GDM NICE risk factors but were screened with an oral GTT. Women with a risk factor that were screened with a GTT had an 8.9% (n=34) prevalence of GDM. Of those that were screened but did not have a risk factor 7.7% (n=20) were diagnosed with GDM. Overall, 2% (54 women) of the cohort had a diagnosis of GDM. Ethnicity was the risk factor most likely to be missed (n=55, 66.3%). The GTT test was completed within the recommended gestational window (24-28 weeks) 56.6% (n=371) of the time. CONCLUSION: This study highlights poor compliance with risk factor screening for GDM in nulliparous women. Further investigation into the underlying reasons is warranted as well as the implications for pregnancy outcome. TRIAL REGISTRATION NUMBER: ACTRN12607000551493. PMID- 26901400 TI - Molecular detection of intrauterine microbial colonization in women with endometriosis. AB - OBJECTIVE: Increased intrauterine microbial colonization by bacteria culture method and occurrence of endometritis have been reported in women with endometriosis. Here we investigated microbial colonization in intrauterine environment and cystic fluid of women with and without endometriosis by molecular approach. STUDY DESIGN: This is a case-controlled biological study with a total of 32 women each with and without endometriosis. Among them, 16 each in these two groups of women received treatment with gonadotropin-releasing hormone agonist (GnRHa). Pattern of microbial colonization in endometrial swabs and endometrioma/non-endometrioma cystic fluid was examined using broad-range polymerase-chain reaction (PCR) amplification of bacteria targeting 16S rRNA gene (rDNA). After quantification of index PCR product, 16S rDNA metagenome sequence analysis was done by Illumina Miseq system. RESULTS: A wide proportion (0.01 97.8%) of multiple bacteria was detected in both endometrial swabs and cystic fluid collected from women with and without endometriosis. 16S metagenome assay indicated that proportion of Lactobacillacae was significantly decreased (p<0.01) and of Streptococcaceae, Staphylococaceae, Enterobacteriaceae was significantly increased (p<0.05 for each) in GnRHa-treated women with endometriosis than in GnRHa-untreated women. While bacteria culture method failed to detect a single colony, 16S metagenome assay could detect significantly higher percentage of Streptococcaceae (p<0.01) and Staphylococaceae (p<0.05) in the cystic fluid derived from women with ovarian endometrioma comparing to that in cystic fluid collected from non-endometrioma cysts. CONCLUSION: These findings indicate the occurrence of sub-clinical infection in intrauterine environment and in the cystic fluid of ovarian endometrioma. Additional side effect of GnRHa treatment in promoting silent intrauterine and/or ovarian infection should be considered. PMID- 26901401 TI - Folic acid supplementation in pregnancy to prevent preterm birth: a systematic review and meta-analysis of randomized controlled trials. AB - Folic acid (FA) may have a role in the prevention of pregnancy complications. However, the efficacy of FA supplementation in reducing the risk of preterm birth (PTB) is still unclear. The aim of this systematic review with meta-analysis was to evaluate the efficacy of folic acid supplementation during pregnancy to prevent preterm birth (PTB). The research protocol was designed a priori, defining methods for searching the literature in electronic databases, including and examining articles, and extracting and analyzing data. We included all randomized trials (RCTs) of asymptomatic singleton gestations without prior PTB who were randomized to prophylactic treatment with either FA supplementation or control (placebo or no treatment). The primary outcome was the incidence of PTB <37 weeks. Five randomized trials including 5,332 asymptomatic singleton gestations without prior PTB were included in the analysis. Women who received FA supplementation had a similar rate of PTB <37 weeks (22.6% vs 22.9%; RR 0.99, 95% CI 0.82-1.18), PTB<34 weeks (7.1% vs 8.7%; RR 0.77, 95% CI 0.55-1.09) and of preterm premature rupture of membranes (2.4% vs 2.9%; RR 0.81, 95% CI 0.44-1.50) compared with control group. Regarding neonatal outcome we found no significant differences in birth weight (mean difference 85.58g, 95% CI -55.17-226.34), low birth weight (21.0% vs 15.1%; RR 0.79, 95% CI 0.49 to 1.28) and perinatal death (2.9% vs 2.4%; RR 0.90, 95% CI 0.60-1.34). In summary, FA supplementation during pregnancy does not prevent PTB <37 weeks. Daily FA supplementation remains the most important intervention to reduce the risk of neural tube defects. PMID- 26901403 TI - Functional metagenomics of extreme environments. AB - The bioprospecting of enzymes that operate under extreme conditions is of particular interest for many biotechnological and industrial processes. Nevertheless, there is a considerable limitation to retrieve novel enzymes as only a small fraction of microorganisms derived from extreme environments can be cultured under standard laboratory conditions. Functional metagenomics has the advantage of not requiring the cultivation of microorganisms or previous sequence information to known genes, thus representing a valuable approach for mining enzymes with new features. In this review, we summarize studies showing how functional metagenomics was employed to retrieve genes encoding for proteins involved not only in molecular adaptation and resistance to extreme environmental conditions but also in other enzymatic activities of biotechnological interest. PMID- 26901402 TI - Genetic Counseling and Testing for Alzheimer's Disease and Frontotemporal Lobar Degeneration: An Italian Consensus Protocol. AB - BACKGROUND: Genetic testing of familial Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD) is attracting interest thanks to innovative primary prevention clinical trials and increased request for information by at-risk individuals. However, ethical, social, and psychological implications are paramount and genetic testing must be supported by structured genetic counseling. In Italy, practice parameters and guidelines for genetic counseling in dementia are not available. OBJECTIVE: To develop a nationally harmonized protocol for genetic counseling and testing of familial AD and FTLD. METHODS: Activities were carried out in the context of the Italian Dominantly Inherited Alzheimer's and Frontotemporal Network (IT-DIAfN) project, a national network of centers of excellence with expertise in managing patients with familial AD and FTLD. A survey of the literature on genetic counseling protocols and guidelines was conducted. Local protocols for genetic counseling were surveyed. Differences and commonalities among protocols were identified and discussed among project partners. Consensus was reached following implicit aggregation methods. RESULTS: Consensus was reached on a protocol for patients with clinically diagnosed familial AD or FTLD and a distinct protocol for their at-risk relatives. Genetic counseling should be provided by a multidisciplinary team including a geneticist, a neurologist/geriatrician, and a psychologist/psychiatrist, according to the following schedule: (i) initial consultation with tailored information on the genetics of the dementias; (ii) clinical, psychological, and cognitive assessment; if deemed appropriate (iii) genetic testing following a structured decision tree for gene mutation search; (iv) genetic testing result disclosure; (v) psychological support follow-up. CONCLUSION: This genetic counseling protocol provides Italian centers with a line of shared practice for dealing with the requests for genetic testing for familial AD and FTLD from patients and at-risk relatives, who may also be eligible participants for novel prevention clinical trials. PMID- 26901404 TI - Perceptions and Practices of Community Pharmacists towards Antimicrobial Stewardship in the State of Selangor, Malaysia. AB - BACKGROUND: Increasing antimicrobial resistance is one of the pressing concerns globally. Injudicious use of antibiotics is one of the modifiable factors responsible for antimicrobial resistance. Given the widespread use of antimicrobials in community settings, pharmacists have an important role in ensuring appropriate use of antibiotics. The objective of this study was to assess the perception and self-reported practices of community pharmacists towards antimicrobial stewardship. METHODS: A cross-sectional study was conducted among community pharmacists between March-April, 2015, using a self-administered, pre-tested questionnaire in the State of Selangor, Malaysia. A simple random sampling approach was used to select pharmacy sites. Descriptive and inferential statistical methods were used to analyse the data. RESULTS: A total of 188 pharmacists responded to the survey, giving a response rate of 83.5%. The majority of participants (n = 182, 96.8%) believed that antimicrobial stewardship program helps healthcare professionals to improve the quality of patient care. However, more than half of pharmacists were neutral in their opinion about the incorporation of antimicrobial stewardship programs in community pharmacies (n = 102, 54.2%). Though collaboration was often done by pharmacists with other health professionals over the use of antibiotics (n = 104, 55.3%), a significant proportion of participants (n = 102, 54.2%) rarely/occasionally participate in antimicrobial awareness campaigns. Pharmacists having postgraduate qualification were more likely to held positive perceptions of, and were engaged in, antimicrobial stewardship than their non-postgraduate counterpart (p<0.05). Similarly, more experienced pharmacists (> 10 years) held positive perceptions towards antimicrobial stewardship (p<0.05). CONCLUSION: The study highlighted some gaps in the perception and practices of community pharmacist towards antimicrobial stewardship. Development of customized interventions would be critical to bridging these gaps and improve their perception and practices towards antimicrobial stewardship. PMID- 26901405 TI - Neuroprotective Effect of a DJ-1 Based Peptide in a Toxin Induced Mouse Model of Multiple System Atrophy. AB - Multiple System Atrophy (MSA) is a sporadic neurodegenerative disorder characterized by parkinsonism, cerebellar ataxia and dysautonomia, in various combinations. In MSA with parkinsonism (MSA-P), the degeneration is mainly restricted to the substantia nigra pars compacta and putamen. Studies have identified alterations in DJ-1 (PARK7), a key component of the anti-oxidative stress response, in Parkinson's disease (PD) and MSA patients. Previously we have shown that a short DJ-1-based peptide named ND-13, protected cultured cells against neurotoxic insults and improved behavioral outcome in animal models of Parkinson's disease (PD). In this study, we used the 3-Nitropropionic acid (3-NP) induced mouse model of MSA and treated the animals with ND-13 in order to evaluate its therapeutic effects. Our results show that ND-13 protects cultured cells against oxidative stress generated by the mitochondrial inhibitor, 3-NP. Moreover, we show that ND-13 attenuates nigrostriatal degeneration and improves performance in motor-related behavioral tasks in 3-NP-treated mice. Our findings suggest a rationale for using ND-13 as a promising therapeutic approach for treatment of MSA. PMID- 26901406 TI - Self-referential schemas and attentional bias predict severity and naturalistic course of depression symptoms. AB - Attentional bias and self-referential schemas have been observed in numerous cross-sectional studies of depressed adults and are theorised to maintain negative mood. However, few longitudinal studies have examined whether maladaptive cognition predicts the course of depressive symptoms. Fifty-seven adults with elevated depression symptoms were assessed for negative attentional bias using a dot-probe task with eye-tracking and self-referential schemas using a self-referent encoding task. Participants subsequently completed five weekly depression symptom assessments. Participants with more negative self-referential schemas had higher baseline depression symptoms (r = .55). However, participants who spent more time attending to negative words showed greater symptom worsening over time (r = .42). The findings for negative self-referential schemas replicate past research, while the findings for negative attention bias represent the first evidence showing that attentional biases predict naturalistic symptom course. This work suggests that negative attention biases maintain depression symptoms and represent an important treatment target for neurocognitive therapeutics. PMID- 26901408 TI - Selective Surface Charge Sign Reversal on Metallic Carbon Nanotubes for Facile Ultrahigh Purity Nanotube Sorting. AB - Semiconducting (semi-) single-walled carbon nanotubes (SWNTs) must be purified of their metallic (met-) counterparts for most applications including nanoelectronics, solar cells, chemical sensors, and artificial skins. Previous bulk sorting techniques are based on subtle contrasts between properties of different nanotube/dispersing agent complexes. We report here a method which directly exploits the nanotube band structure differences. For the heterogeneous redox reaction of SWNTs with oxygen/water couple, the aqueous pH can be tuned so that the redox kinetics is determined by the availability of nanotube electrons only at/near the Fermi level, as predicted quantitatively by the Marcus-Gerischer (MG) theory. Consequently, met-SWNTs oxidize much faster than semi-SWNTs and only met-SWNTs selectively reverse the sign of their measured surface zeta potential from negative to positive at the optimized acidic pH when suspended with nonionic surfactants. By passing the redox-reacted nanotubes through anionic hydrogel beads, we isolate semi-SWNTs to record high electrically verified purity above 99.94% +/- 0.04%. This facile charge sign reversal (CSR)-based sorting technique is robust and can sort SWNTs with a broad diameter range. PMID- 26901407 TI - Prospective identification of neoantigen-specific lymphocytes in the peripheral blood of melanoma patients. AB - Detection of lymphocytes that target tumor-specific mutant neoantigens--derived from products encoded by mutated genes in the tumor--is mostly limited to tumor resident lymphocytes, but whether these lymphocytes often occur in the circulation is unclear. We recently reported that intratumoral expression of the programmed cell death 1 (PD-1) receptor can guide the identification of the patient-specific repertoire of tumor-reactive CD8(+) lymphocytes that reside in the tumor. In view of these findings, we investigated whether PD-1 expression on peripheral blood lymphocytes could be used as a biomarker to detect T cells that target neoantigens. By using a high-throughput personalized screening approach, we identified neoantigen-specific lymphocytes in the peripheral blood of three of four melanoma patients. Despite their low frequency in the circulation, we found that CD8(+)PD-1(+), but not CD8(+)PD-1(-), cell populations had lymphocytes that targeted 3, 3 and 1 unique, patient-specific neoantigens, respectively. We show that neoantigen-specific T cells and gene-engineered lymphocytes expressing neoantigen-specific T cell receptors (TCRs) isolated from peripheral blood recognized autologous tumors. Notably, the tumor-antigen specificities and TCR repertoires of the circulating and tumor-infiltrating CD8(+)PD-1(+) cells appeared similar, implying that the circulating CD8(+)PD-1(+) lymphocytes could provide a window into the tumor-resident antitumor lymphocytes. Thus, expression of PD-1 identifies a diverse and patient-specific antitumor T cell response in peripheral blood, providing a novel noninvasive strategy to develop personalized therapies using neoantigen-reactive lymphocytes or TCRs to treat cancer. PMID- 26901409 TI - Systematic Review of Methods in Low-Consensus Fields: Supporting Commensuration through 'Construct-Centered Methods Aggregation' in the Case of Climate Change Vulnerability Research. AB - There is increasing interest in using systematic review to synthesize evidence on the social and environmental effects of and adaptations to climate change. Use of systematic review for evidence in this field is complicated by the heterogeneity of methods used and by uneven reporting. In order to facilitate synthesis of results and design of subsequent research a method, construct-centered methods aggregation, was designed to 1) provide a transparent, valid and reliable description of research methods, 2) support comparability of primary studies and 3) contribute to a shared empirical basis for improving research practice. Rather than taking research reports at face value, research designs are reviewed through inductive analysis. This involves bottom-up identification of constructs, definitions and operationalizations; assessment of concepts' commensurability through comparison of definitions; identification of theoretical frameworks through patterns of construct use; and integration of transparently reported and valid operationalizations into ideal-type research frameworks. Through the integration of reliable bottom-up inductive coding from operationalizations and top-down coding driven from stated theory with expert interpretation, construct centered methods aggregation enabled both resolution of heterogeneity within identically named constructs and merging of differently labeled but identical constructs. These two processes allowed transparent, rigorous and contextually sensitive synthesis of the research presented in an uneven set of reports undertaken in a heterogenous field. If adopted more broadly, construct-centered methods aggregation may contribute to the emergence of a valid, empirically grounded description of methods used in primary research. These descriptions may function as a set of expectations that improves the transparency of reporting and as an evolving comprehensive framework that supports both interpretation of existing and design of future research. PMID- 26901410 TI - Constrained Total Generalized p-Variation Minimization for Few-View X-Ray Computed Tomography Image Reconstruction. AB - Total generalized variation (TGV)-based computed tomography (CT) image reconstruction, which utilizes high-order image derivatives, is superior to total variation-based methods in terms of the preservation of edge information and the suppression of unfavorable staircase effects. However, conventional TGV regularization employs l1-based form, which is not the most direct method for maximizing sparsity prior. In this study, we propose a total generalized p variation (TGpV) regularization model to improve the sparsity exploitation of TGV and offer efficient solutions to few-view CT image reconstruction problems. To solve the nonconvex optimization problem of the TGpV minimization model, we then present an efficient iterative algorithm based on the alternating minimization of augmented Lagrangian function. All of the resulting subproblems decoupled by variable splitting admit explicit solutions by applying alternating minimization method and generalized p-shrinkage mapping. In addition, approximate solutions that can be easily performed and quickly calculated through fast Fourier transform are derived using the proximal point method to reduce the cost of inner subproblems. The accuracy and efficiency of the simulated and real data are qualitatively and quantitatively evaluated to validate the efficiency and feasibility of the proposed method. Overall, the proposed method exhibits reasonable performance and outperforms the original TGV-based method when applied to few-view problems. PMID- 26901411 TI - Genocide Exposure and Subsequent Suicide Risk: A Population-Based Study. AB - The association between periods of genocide-related exposures and suicide risk remains unknown. Our study tests that association using a national population based study design. The source population comprised of all persons born during1922-1945 in Nazi-occupied or dominated European nations, that immigrated to Israel by 1965, were identified in the Population Register (N = 220,665), and followed up for suicide to 2014, totaling 16,953,602 person-years. The population was disaggregated to compare a trauma gradient among groups that immigrated before (indirect, n = 20,612, 9%); during (partial direct, n = 17,037, 8%); or after (full direct, n = 183,016, 83%) exposure to the Nazi era. Also, the direct exposure groups were examined regarding pre- or post-natal exposure periods. Cox regression models were used to compute Hazard Ratios (HR) of suicide risk to compare the exposure groups, adjusting for confounding by gender, residential SES and history of psychiatric hospitalization. In the total population, only the partial direct exposure subgroup was at greater risk compared to the indirect exposure group (HR = 1.73, 95% CI, 1.10, 2.73; P < .05). That effect replicated in six sensitivity analyses. In addition, sensitivity analyses showed that exposure at ages 13 plus among females, and follow-up by years since immigration were associated with a greater risk; whereas in utero exposure among persons with no psychiatric hospitalization and early postnatal exposure among males were at a reduced risk. Tentative mechanisms impute biopsychosocial vulnerability and natural selection during early critical periods among males, and feelings of guilt and entrapment or defeat among females. PMID- 26901412 TI - Children Reading to Dogs: A Systematic Review of the Literature. AB - BACKGROUND: Despite growing interest in the value of human-animal interactions (HAI) to human mental and physical health the quality of the evidence on which postulated benefits from animals to human psychological health are based is often unclear. To date there exist no systematic reviews on the effects of HAI in educational settings specifically focussing on the perceived benefits to children of reading to dogs. With rising popularity and implementation of these programmes in schools, it is essential that the evidence base exploring the pedagogic value of these initiatives is well documented. METHODS: Using PRISMA guidelines we systematically investigated the literature reporting the pedagogic effects of reading to dogs. Because research in this area is in the early stages of scientific enquiry we adopted broad inclusion criteria, accepting all reports which discussed measurable effects related to the topic that were written in English. Multiple online databases were searched during January-March 2015; grey literature searches were also conducted. The search results which met the inclusion criteria were evaluated, and discussed, in relation to the Oxford Centre for Evidence Based Medicine levels of evidence; 27 papers were classified as Level 5, 13 as Level 4, 7 as Level 2c and 1 as Level 2b. CONCLUSION: The evidence suggests that reading to a dog may have a beneficial effect on a number of behavioural processes which contribute to a positive effect on the environment in which reading is practiced, leading to improved reading performance. However, the evidence base on which these inferences are made is of low quality. There is a clear need for the use of higher quality research methodologies and the inclusion of appropriate controls in order to draw causal inferences on whether or how reading to dogs may benefit children's reading practices. The mechanisms for any effect remain a matter of conjecture. PMID- 26901413 TI - IL-17 Induction by ArtinM is Due to Stimulation of IL-23 and IL-1 Release and/or Interaction with CD3 in CD4+ T Cells. AB - ArtinM is a D-mannose-binding lectin extracted from the seeds of Artocarpus heterophyllus that interacts with TLR2 N-glycans and activates antigen-presenting cells (APCs), as manifested by IL-12 production. In vivo ArtinM administration induces Th1 immunity and confers protection against infection with several intracellular pathogens. In the murine model of Candida albicans infection, it was verified that, in addition to Th1, ArtinM induces Th17 immunity manifested by high IL-17 levels in the treated animals. Herein, we investigated the mechanisms accounting for the ArtinM-induced IL-17 production. We found that ArtinM stimulates the IL-17 production by spleen cells in BALB/c or C57BL/6 mice, a response that was significantly reduced in the absence of IL-23, MyD88, or IL-1R. Furthermore, we showed that ArtinM directly induced the IL-23 mRNA expression and the IL-1 production by macrophages. Consistently, in cell suspensions depleted of macrophages, the IL-17 production stimulated by ArtinM was reduced by 53% and the exogenous IL-23 acted synergistically with ArtinM in promoting IL-17 production by spleen cell suspensions. We verified that the absence of IL-23, IL-1R, or MyD88 inhibited, but did not block, the IL-17 production by ArtinM-stimulated spleen cells. Therefore, we investigated whether ArtinM exerts a direct effect on CD4+ T cells in promoting IL-17 production. Indeed, spleen cell suspensions depleted of CD4+ T cells responded to ArtinM with very low levels of IL-17 release. Likewise, isolated CD4+ T cells under ArtinM stimulus augmented the expression of TGF-beta mRNA and released high levels of IL-17. Considering the observed synergism between IL-23 and ArtinM, we used cells from IL-23 KO mice to assess the direct effect of lectin on CD4+ T cells. We verified that ArtinM increased the IL-17 production significantly, a response that was inhibited when the CD4+ T cells were pre-incubated with anti-CD3 antibody. In conclusion, ArtinM stimulates the production of IL-17 by CD4+ T cells in two major ways: (I) through the induction of IL-23 and IL-1 by APCs and (II) through the direct interaction with CD3 on the CD4+ T cells. This study contributes to elucidation of mechanisms accounting for the property of ArtinM in inducing Th17 immunity and opens new perspectives in designing strategies for modulating immunity by using carbohydrate recognition agents. PMID- 26901414 TI - Various checkpoints prevent the synthesis of Staphylococcus aureus peptidoglycan hydrolase LytM in the stationary growth phase. AB - In Staphylococcus aureus, peptidoglycan metabolism plays a role in the host inflammatory response and pathogenesis. Transcription of the peptidoglycan hydrolases is activated by the essential 2-component system WalKR at low cell density. During stationary growth phase, WalKR is not active and transcription of the peptidoglycan hydrolase genes is repressed. In this work, we studied regulation of expression of the glycylglycine endopeptidase LytM. We show that, in addition to the transcriptional regulation mediated by WalKR, the synthesis of LytM is negatively controlled by a unique mechanism at the stationary growth phase. We have identified 2 different mRNAs encoding lytM, which vary in the length of their 5' untranslated (5'UTR) regions. LytM is predominantly produced from the WalKR-regulated mRNA transcript carrying a short 5'UTR. The lytM mRNA is also transcribed as part of a polycistronic operon with the upstream SA0264 gene and is constitutively expressed. Although SA0264 protein can be synthesized from the longer operon transcript, lytM cannot be translated because its ribosome binding site is sequestered into a translationally inactive secondary structure. In addition, the effector of the agr system, RNAIII, can inhibit translation of lytM present on the operon without altering the transcript level but does not have an effect on the translation of the upstream gene. We propose that this dual regulation of lytM expression, at the transcriptional and post-transcriptional levels, contributes to prevent cell wall damage during the stationary phase of growth. PMID- 26901415 TI - Using "On/Off" (19)F NMR/Magnetic Resonance Imaging Signals to Sense Tyrosine Kinase/Phosphatase Activity in Vitro and in Cell Lysates. AB - Tyrosine kinase and phosphatase are two important, antagonistic enzymes in organisms. Development of noninvasive approach for sensing their activity with high spatial and temporal resolution remains challenging. Herein, we rationally designed a hydrogelator Nap-Phe-Phe(CF3)-Glu-Tyr-Ile-OH (1a) whose supramolecular hydrogel (i.e., Gel 1a) can be subjected to tyrosine kinase-directed disassembly, and its phosphate precursor Nap-Phe-Phe(CF3)-Glu-Tyr(H2PO3)-Ile-OH (1b), which can be subjected to alkaline phosphatase (ALP)-instructed self-assembly to form supramolecular hydrogel Gel 1b, respectively. Mechanic properties and internal fibrous networks of the hydrogels were characterized with rheology and cryo transmission electron microscopy (cryo-TEM). Disassembly/self-assembly of their corresponding supramolecular hydrogels conferring respective "On/Off" (19)F NMR/MRI signals were employed to sense the activity of these two important enzymes in vitro and in cell lysates for the first time. We anticipate that our new (19)F NMR/magnetic resonance imaging (MRI) method would facilitate pharmaceutical researchers to screen new inhibitors for these two enzymes without steric hindrance. PMID- 26901421 TI - Individually Dispersed Wood-Based Cellulose Nanocrystals. AB - Good dispersion of cellulose nanocrystals (CNCs) in the polymer matrix is one of the key factors to obtaining good properties in the resulting nanocomposites. However, the preparation of individually dispersed CNCs in solvents or in polymer matrices has been a challenge. In this study, individually dispersed wood-based CNCs have been successfully prepared in solvents, including dimethylformamide (DMF), H2O, and a mixture of H2O/DMF, by sonication of moisture-containing CNCs. The CNCs dispersions were characterized by dynamic light scattering (DLS). It is found that CNCs containing above about 3.8 wt % moisture is critical for achieving individually dispersed CNC in solvents. Hydrodynamic radius (Rh) of CNCs is smaller in H2O/DMF co-solvent mixture than that in pure DMF or in pure H2O under same sonication treatment conditions. Experimental results have been corroborated using molecular simulation study. PMID- 26901417 TI - Long Term Outcomes of a Geriatric Liaison Intervention in Frail Elderly Cancer Patients. AB - BACKGROUND: The aim of this study was to evaluate the long term effects after discharge of a hospital-based geriatric liaison intervention to prevent postoperative delirium in frail elderly cancer patients treated with an elective surgical procedure for a solid tumour. In addition, the effect of a postoperative delirium on long term outcomes was examined. METHODS: A three month follow-up was performed in participants of the Liaison Intervention in Frail Elderly study, a multicentre, prospective, randomized, controlled trial. Patients were randomized to standard treatment or a geriatric liaison intervention. The intervention consisted of a preoperative geriatric consultation, an individual treatment plan targeted at risk factors for delirium and daily visits by a geriatric nurse during the hospital stay. The long term outcomes included: mortality, rehospitalisation, Activities of Daily Living (ADL) functioning, return to the independent pre-operative living situation, use of supportive care, cognitive functioning and health related quality of life. RESULTS: Data of 260 patients (intervention n = 127, Control n = 133) were analysed. There were no differences between the intervention group and usual-care group for any of the outcomes three months after discharge. The presence of postoperative delirium was associated with: an increased risk of decline in ADL functioning (OR: 2.65, 95% CI: 1.02 6.88), an increased use of supportive assistance (OR: 2.45, 95% CI: 1.02-5.87) and a decreased chance to return to the independent preoperative living situation (OR: 0.18, 95% CI: 0.07-0.49). CONCLUSIONS: A hospital-based geriatric liaison intervention for the prevention of postoperative delirium in frail elderly cancer patients undergoing elective surgery for a solid tumour did not improve outcomes 3 months after discharge from hospital. The negative effect of a postoperative delirium on late outcome was confirmed. TRIAL REGISTRATION: Nederlands Trial Register, Trial ID NTR 823. PMID- 26901416 TI - C-terminal Src Kinase Gates Homeostatic Synaptic Plasticity and Regulates Fasciclin II Expression at the Drosophila Neuromuscular Junction. AB - Forms of homeostatic plasticity stabilize neuronal outputs and promote physiologically favorable synapse function. A well-studied homeostatic system operates at the Drosophila melanogaster larval neuromuscular junction (NMJ). At the NMJ, impairment of postsynaptic glutamate receptor activity is offset by a compensatory increase in presynaptic neurotransmitter release. We aim to elucidate how this process operates on a molecular level and is preserved throughout development. In this study, we identified a tyrosine kinase-driven signaling system that sustains homeostatic control of NMJ function. We identified C-terminal Src Kinase (Csk) as a potential regulator of synaptic homeostasis through an RNAi- and electrophysiology-based genetic screen. We found that Csk loss-of-function mutations impaired the sustained expression of homeostatic plasticity at the NMJ, without drastically altering synapse growth or baseline neurotransmission. Muscle-specific overexpression of Src Family Kinase (SFK) substrates that are negatively regulated by Csk also impaired NMJ homeostasis. Surprisingly, we found that transgenic Csk-YFP can support homeostatic plasticity at the NMJ when expressed either in the muscle or in the nerve. However, only muscle-expressed Csk-YFP was able to localize to NMJ structures. By immunostaining, we found that Csk mutant NMJs had dysregulated expression of the Neural Cell Adhesion Molecule homolog Fasciclin II (FasII). By immunoblotting, we found that levels of a specific isoform of FasII were decreased in homeostatically challenged GluRIIA mutant animals-but markedly increased in Csk mutant animals. Additionally, we found that postsynaptic overexpression of FasII from its endogenous locus was sufficient to impair synaptic homeostasis, and genetically reducing FasII levels in Csk mutants fully restored synaptic homeostasis. Based on these data, we propose that Csk and its SFK substrates impinge upon homeostatic control of NMJ function by regulating downstream expression or localization of FasII. PMID- 26901422 TI - Power Analysis for Population-Based Longitudinal Studies Investigating Gene Environment Interactions in Chronic Diseases: A Simulation Study. AB - Conventional methods for sample size calculation for population-based longitudinal studies tend to overestimate the statistical power by overlooking important determinants of the required sample size, such as the measurement errors and unmeasured etiological determinants, etc. In contrast, a simulation based sample size calculation, if designed properly, allows these determinants to be taken into account and offers flexibility in accommodating complex study design features. The Canadian Longitudinal Study on Aging (CLSA) is a Canada wide, 20-year follow-up study of 30,000 people between the ages of 45 and 85 years, with in-depth information collected every 3 years. A simulation study, based on an illness-death model, was conducted to: (1) investigate the statistical power profile of the CLSA to detect the effect of environmental and genetic risk factors, and their interaction on age-related chronic diseases; and (2) explore the design alternatives and implementation strategies for increasing the statistical power of population-based longitudinal studies in general. The results showed that the statistical power to identify the effect of environmental and genetic risk exposures, and their interaction on a disease was boosted when: (1) the prevalence of the risk exposures increased; (2) the disease of interest is relatively common in the population; and (3) risk exposures were measured accurately. In addition, the frequency of data collection every three years in the CLSA led to a slightly lower statistical power compared to the design assuming that participants underwent health monitoring continuously. The CLSA had sufficient power to detect a small (1=0.1) and the disease of interest was not rare (such as diabetes and dementia). The CLSA had enough power to detect a large effect of the gene-environment interaction only when both risk exposures had relatively high prevalence (0.2) and the disease of interest was very common (such as diabetes). The minimum detectable hazard ratios (MDHR) of the CLSA for the environmental and genetic risk exposures obtained from this simulation study were larger than those calculated according to the conventional sample size calculation method. For example, the MDHR for the environmental risk exposure was 1.15 according to the conventional method if the prevalence of the risk exposure was 0.1 and the disease of interest was dementia. In contrast, the MDHR was 1.61 if the same exposure was measured every 3 years with a misclassification rate of 0.1 according to this simulation study. With a given sample size, higher statistical power could be achieved by increasing the measuring frequency in participants with high risk of declining health status or changing risk exposures, and by increasing measurement accuracy of diseases and risk exposures. A properly designed simulation-based sample size calculation is superior to conventional methods when rigorous sample size calculation is necessary. PMID- 26901424 TI - Endoluminal calprotectin measurement in assessment of pouchitis and a new index of disease activity: a pilot study. AB - Pouchitis is the most common complication following proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis (UC). To provide a standardized definition of pouchitis clinical, endoscopic and histological markers were grouped and weighted in the pouch disease activity index (PDAI). However, the delay in the assessment of the final score due to the time requested for histological analysis remains the main obstacle to the index implementation in clinical practice so that the use of modified-PDAI (mPDAI) with exclusion of histologic subscore has been proposed. We tested the ability of calprotectin measurement in the pouch endoluminal content to mimic the histologic score as defined in the PDAI, the index that we adopted as gold standard for pouchitis diagnosis. Calprotectin was measured by ELISA in the pouch endoluminal content collected during endoscopy in 40 consecutive patients with J-pouch. In each patient PDAI and mPDAI were calculated and 15% of patients were erroneously classified by mPDAI. ROC analysis of calprotectin values vs. acute histological subscore >= 3 identified different calprotectin cut-off values with corresponding sensitivity and specificity allowing the definition and scoring of different range of calprotectin subscores. We incorporated the calprotectin score in the mPDAI obtaining a new score that shows the same specificity as PDAI for diagnosis of pouchitis and higher sensitivity when compared with mPDAI. The use of the proposed new score, once validated in a larger series of patients, might be useful in the early management of patients with symptoms of pouchitis. PMID- 26901423 TI - Muscle Strength and Fitness in Pediatric Obesity: a Systematic Review from the European Childhood Obesity Group. AB - The increasing prevalence of paediatric obesity and related metabolic complications has been mainly associated with lower aerobic fitness while less is known regarding potential musculoskeletal impairments. The purpose of the present systematic review was to report the evidence regarding muscular fitness in children and adolescents with obesity. A systematic article search was conducted between November 2014 and June 2015 using MEDLINE, EMBASE, CINAHL psycINFO, SPORTDiscus and SocINDEX. Articles published in English and reporting results on muscle strength and muscular fitness in children and adolescents aged 6 to 18 years were eligible. Of 548 identified titles, 36 studies were included for analyses. While laboratory-based studies described higher absolute muscular fitness in youth with obesity compared with their lean peers, these differences are negated when corrected for body weight and lean mass, then supporting field based investigations. All interventional studies reviewed led to improved muscular fitness in youth with obesity. Children and adolescents with obesity display impaired muscular fitness compared to healthy-weight peers, which seems mainly due to factors such as excessive body weight and increased inertia of the body. Our analysis also points out the lack of information regarding the role of age, maturation or sex in the current literature and reveals that routinely used field tests analysing overall daily muscular fitness in children with obesity provide satisfactory results when compared to laboratory-based data. PMID- 26901425 TI - Cortical Reorganisation during a 30-Week Tinnitus Treatment Program. AB - Subjective tinnitus is characterised by the conscious perception of a phantom sound. Previous studies have shown that individuals with chronic tinnitus have disrupted sound-evoked cortical tonotopic maps, time-shifted evoked auditory responses, and altered oscillatory cortical activity. The main objectives of this study were to: (i) compare sound-evoked brain responses and cortical tonotopic maps in individuals with bilateral tinnitus and those without tinnitus; and (ii) investigate whether changes in these sound-evoked responses occur with amelioration of the tinnitus percept during a 30-week tinnitus treatment program. Magnetoencephalography (MEG) recordings of 12 bilateral tinnitus participants and 10 control normal-hearing subjects reporting no tinnitus were recorded at baseline, using 500 Hz, 1000 Hz, 2000 Hz, and 4000 Hz tones presented monaurally at 70 dBSPL through insert tube phones. For the tinnitus participants, MEG recordings were obtained at 5-, 10-, 20- and 30- week time points during tinnitus treatment. Results for the 500 Hz and 1000 Hz sources (where hearing thresholds were within normal limits for all participants) showed that the tinnitus participants had a significantly larger and more anteriorly located source strengths when compared to the non-tinnitus participants. During the 30-week tinnitus treatment, the participants' 500 Hz and 1000 Hz source strengths remained higher than the non-tinnitus participants; however, the source locations shifted towards the direction recorded from the non-tinnitus control group. Further, in the left hemisphere, there was a time-shifted association between the trajectory of change of the individual's objective (source strength and anterior posterior source location) and subjective measures (using tinnitus reaction questionnaire, TRQ). The differences in source strength between the two groups suggest that individuals with tinnitus have enhanced central gain which is not significantly influenced by the tinnitus treatment, and may result from the hearing loss per se. On the other hand, the shifts in the tonotopic map towards the non-tinnitus participants' source location suggests that the tinnitus treatment might reduce the disruptions in the map, presumably produced by the tinnitus percept directly or indirectly. Further, the similarity in the trajectory of change across the objective and subjective parameters after time shifting the perceptual changes by 5 weeks suggests that during or following treatment, perceptual changes in the tinnitus percept may precede neurophysiological changes. Subgroup analyses conducted by magnitude of hearing loss suggest that there were no differences in the 500 Hz and 1000 Hz source strength amplitudes for the mild-moderate compared with the mild-severe hearing loss subgroup, although the mean source strength was consistently higher for the mild-severe subgroup. Further, the mild-severe subgroup had 500 Hz and 1000 Hz source locations located more anteriorly (i.e., more disrupted compared to the control group) compared to the mild-moderate group, although this was trending towards significance only for the 500Hz left hemisphere source. While the small numbers of participants within the subgroup analyses reduce the statistical power, this study suggests that those with greater magnitudes of hearing loss show greater cortical disruptions with tinnitus and that tinnitus treatment appears to reduce the tonotopic map disruptions but not the source strength (or central gain). PMID- 26901426 TI - Caffeine Intake Is Associated with Urinary Incontinence in Korean Postmenopausal Women: Results from the Korean National Health and Nutrition Examination Survey. AB - INTRODUCTION: The objective of this study was to investigate whether caffeine intake is associated with urinary incontinence (UI) and quality of life (QOL) in Korean postmenopausal women. MATERIALS AND METHODS: We included 4,028 postmenopausal women who had participated in the Korea National Health and Nutrition Examination Survey IV (KNHANES IV). From the KNHANES questionnaire data, we ascertained the UI status of participants, defined as self-reported or medically diagnosed UI, and calculated their total daily caffeine intake through questions regarding the frequency of food consumption. The EuroQoL-5 Dimension (EQ-5D) descriptive system was used to evaluate QOL among the study population. RESULTS: The mean age of the study population was 63.19+/-0.25 years. Among the 4,028 women, the prevalence of medically diagnosed UI was 2.6% (n = 151), the prevalence of self-reported UI was 11.9% (n = 483), and the lifetime prevalence of UI was 15.8% (n = 639). In the study population, the presence of UI was not significantly different by age group, but daily caffeine consumption and the percentage of caffeine consumer decreased with age (P<0.001). Higher caffeine intake led to significantly higher prevalence of both medically diagnosed UI (p = 0.012) and self-reported UI (p = 0.040) in the study population. Even after adjusting for factors including age, parity, smoking status, hypertension and diabetes in logistic regression analysis, the positive association between caffeine intake and UI prevalence was observed in both medically diagnosed UI and self-reported UI (P = 0.017) among participants. In a subgroup analysis for EQ-5D (using continuous variables) in which we categorized participants into four groups according to UI presence and caffeine consumption, the EQ-5D scores were lower in the caffeine non-user group with UI than in the caffeine consumer group with or without UI. CONCLUSION: In a sample of Korean postmenopausal women, the prevalence of UI increased with higher caffeine consumption. Additionally, QOL was lower in caffeine non-users with UI than in the caffeine consumer groups. However, additional prospective studies are required to identify clear causation between caffeine consumption, UI prevalence and QOL. PMID- 26901427 TI - Effect of inhaled steroids on laryngeal microflora. AB - Conclusions As is known, this study is the first study to evaluate the effect of inhaled steroids on laryngeal microflora. The data support that ICS usage causes changes in the larynx microflora. Purpose The aim of this study was to determine the alteration in larynx microbial flora of the patients treated with ICS comparing the culture results of a control group. In addition, laryngeal microflora was compared to the smears obtained from the vallecula and pharynx. Materials and methods The study included 39 patients (mean age = 45.56 +/- 12.76 years) who had been using a corticosteroid inhaler and control group consisting of 27 persons (mean age = 43.07 +/- 13.23 years). Culture samples were obtained from the pharynx, larynx, and vallecula in the patient and control groups, and they were evaluated in the microbiology laboratory. Obtained culture results were named by the same microbiologist according to the basic microorganism classification method. Results Coagulase-negative staphylococci (CNS), Streptococcus viridians (VGS) and candida albicans were detected to grow significantly more in the patient group in all three anatomic localizations compared to the control group. Neisseria spp, basillus spp, and Non-viridans alpha-hemolytic streptococcus were detected to grow significantly more in the control group in all three anatomic localizations compared to the patient group. PMID- 26901428 TI - Comparative Analysis of Technologies for Quantifying Extracellular Vesicles (EVs) in Clinical Cerebrospinal Fluids (CSF). AB - Extracellular vesicles (EVs) have emerged as a promising biomarker platform for glioblastoma patients. However, the optimal method for quantitative assessment of EVs in clinical bio-fluid remains a point of contention. Multiple high-resolution platforms for quantitative EV analysis have emerged, including methods grounded in diffraction measurement of Brownian motion (NTA), tunable resistive pulse sensing (TRPS), vesicle flow cytometry (VFC), and transmission electron microscopy (TEM). Here we compared quantitative EV assessment using cerebrospinal fluids derived from glioblastoma patients using these methods. For EVs <150 nm in diameter, NTA detected more EVs than TRPS in three of the four samples tested. VFC particle counts are consistently 2-3 fold lower than NTA and TRPS, suggesting contribution of protein aggregates or other non-lipid particles to particle count by these platforms. While TEM yield meaningful data in terms of the morphology, its particle count are consistently two orders of magnitude lower relative to counts generated by NTA and TRPS. For larger particles (>150 nm in diameter), NTA consistently detected lower number of EVs relative to TRPS. These results unveil the strength and pitfalls of each quantitative method alone for assessing EVs derived from clinical cerebrospinal fluids and suggest that thoughtful synthesis of multi-platform quantitation will be required to guide meaningful clinical investigations. PMID- 26901430 TI - Cell-free multi-layered collagen-based scaffolds demonstrate layer specific regeneration of functional osteochondral tissue in caprine joints. AB - Developing repair strategies for osteochondral tissue presents complex challenges due to its interfacial nature and complex zonal structure, consisting of subchondral bone, intermediate calcified cartilage and the superficial cartilage regions. In this study, the long term ability of a multi-layered biomimetic collagen-based scaffold to repair osteochondral defects is investigated in a large animal model: namely critical sized lateral trochlear ridge (TR) and medial femoral condyle (MC) defects in the caprine stifle joint. The study thus presents the first data in a clinically applicable large animal model. Scaffold fixation and early integration was demonstrated at 2 weeks post implantation. Macroscopic analysis demonstrated improved healing in the multi-layered scaffold group compared to empty defects and a market approved synthetic polymer osteochondral scaffold groups at 6 and 12 months post implantation. Radiological analysis demonstrated superior subchondral bone formation in both defect sites in the multi-layered scaffold group as early as 3 months, with complete regeneration of subchondral bone by 12 months. Histological analysis confirmed the formation of well-structured subchondral trabecular bone and hyaline-like cartilage tissue in the multi-layered scaffold group by 12 months with restoration of the anatomical tidemark. Demonstration of improved healing following treatment with this natural polymer scaffold, through the recruitment of host cells with no requirement for pre-culture, shows the potential of this device for the treatment of patients presenting with osteochondal lesions. PMID- 26901429 TI - One-pot synthesis of pH-responsive hybrid nanogel particles for the intracellular delivery of small interfering RNA. AB - This report describes a novel, one-pot synthesis of hybrid nanoparticles formed by a nanostructured inorganic silica core and an organic pH-responsive hydrogel shell. This easy-to-perform, oil-in-water emulsion process synthesizes fluorescently-doped silica nanoparticles wrapped within a tunable coating of cationic poly(2-diethylaminoethyl methacrylate) hydrogel in one step. Transmission electron microscopy and dynamic light scattering analysis demonstrated that the hydrogel-coated nanoparticles are uniformly dispersed in the aqueous phase. The formation of covalent chemical bonds between the silica and the polymer increases the stability of the organic phase around the inorganic core as demonstrated by thermogravimetric analysis. The cationic nature of the hydrogel is responsible for the pH buffering properties of the nanostructured system and was evaluated by titration experiments. Zeta-potential analysis demonstrated that the charge of the system was reversed when transitioned from acidic to basic pH and vice versa. Consequently, small interfering RNA (siRNA) can be loaded and released in an acidic pH environment thereby enabling the hybrid particles and their payload to avoid endosomal sequestration and enzymatic degradation. These nanoparticles, loaded with specific siRNA molecules directed towards the transcript of the membrane receptor CXCR4, significantly decreased the expression of this protein in a human breast cancer cell line (i.e., MDA-MB 231). Moreover, intravenous administration of siRNA-loaded nanoparticles demonstrated a preferential accumulation at the tumor site that resulted in a reduction of CXCR4 expression. PMID- 26901432 TI - Structure of Thermobifida fusca DyP-type peroxidase and activity towards Kraft lignin and lignin model compounds. AB - A Dyp-type peroxidase enzyme from thermophilic cellulose degrader Thermobifida fusca (TfuDyP) was investigated for catalytic ability towards lignin oxidation. TfuDyP was characterised kinetically against a range of phenolic substrates, and a compound I reaction intermediate was observed via pre-steady state kinetic analysis at lambdamax 404 nm. TfuDyP showed reactivity towards Kraft lignin, and was found to oxidise a beta-aryl ether lignin model compound, forming an oxidised dimer. A crystal structure of TfuDyP was determined, to 1.8 A resolution, which was found to contain a diatomic oxygen ligand bound to the heme centre, positioned close to active site residues Asp-203 and Arg-315. The structure contains two channels providing access to the heme cofactor for organic substrates and hydrogen peroxide. Site-directed mutant D203A showed no activity towards phenolic substrates, but reduced activity towards ABTS, while mutant R315Q showed no activity towards phenolic substrates, nor ABTS. PMID- 26901431 TI - Venous Thromboembolism and Cerebrovascular Events in Patients with Giant Cell Arteritis: A Population-Based Retrospective Cohort Study. AB - OBJECTIVE: To investigate the incidence of venous thromboembolism (VTE) and cerebrovascular events in a community-based incidence cohort of patients with giant cell arteritis (GCA) compared to the general population. METHODS: A population-based inception cohort of patients with incident GCA between January 1, 1950 and December 31, 2009 in Olmsted County, Minnesota and a cohort of non GCA subjects from the same population were assembled and followed until December 31, 2013. Confirmed VTE and cerebrovascular events were identified through direct medical record review. RESULTS: The study population included 244 patients with GCA with a mean +/- SD age at diagnosis of 76.2 +/- 8.2 years (79% women) and an average length of follow-up of 10.2 +/- 6.8 years. Compared to non-GCA subjects of similar age and sex, patients diagnosed with GCA had a higher incidence (%) of amaurosis fugax (cumulative incidence +/- SE: 2.1 +/- 0.9 versus 0, respectively; p = 0.014) but similar rates of stroke, transient ischemic attack (TIA), and VTE. Among patients with GCA, neither baseline characteristics nor laboratory parameters at diagnosis reliably predicted risk of VTE or cerebrovascular events. CONCLUSION: In this population-based study, the incidence of VTE, stroke and TIA was similar in patients with GCA compared to non-GCA subjects. PMID- 26901433 TI - Designing proteins to combat disease: Cardiac troponin C as an example. AB - Throughout history, muscle research has led to numerous scientific breakthroughs that have brought insight to a more general understanding of all biological processes. Potentially one of the most influential discoveries was the role of the second messenger calcium and its myriad of handling and sensing systems that mechanistically control muscle contraction. In this review we will briefly discuss the significance of calcium as a universal second messenger along with some of the most common calcium binding motifs in proteins, focusing on the EF hand. We will also describe some of our approaches to rationally design calcium binding proteins to palliate, or potentially even cure cardiovascular disease. Considering not all failing hearts have the same etiology, genetic background and co-morbidities, personalized therapies will need to be developed. We predict designer proteins will open doors for unprecedented personalized, and potentially, even generalized medicines as gene therapy or protein delivery techniques come to fruition. PMID- 26901434 TI - Pitchfork and Gprasp2 Target Smoothened to the Primary Cilium for Hedgehog Pathway Activation. AB - The seven-transmembrane receptor Smoothened (Smo) activates all Hedgehog (Hh) signaling by translocation into the primary cilia (PC), but how this is regulated is not well understood. Here we show that Pitchfork (Pifo) and the G protein coupled receptor associated sorting protein 2 (Gprasp2) are essential components of an Hh induced ciliary targeting complex able to regulate Smo translocation to the PC. Depletion of Pifo or Gprasp2 leads to failure of Smo translocation to the PC and lack of Hh target gene activation. Together, our results identify a novel protein complex that is regulated by Hh signaling and required for Smo ciliary trafficking and Hh pathway activation. PMID- 26901435 TI - The Effects of Sub-Regional Climate Velocity on the Distribution and Spatial Extent of Marine Species Assemblages. AB - Many studies illustrate variable patterns in individual species distribution shifts in response to changing temperature. However, an assemblage, a group of species that shares a common environmental niche, will likely exhibit similar responses to climate changes, and these community-level responses may have significant implications for ecosystem function. Therefore, we examine the relationship between observed shifts of species in assemblages and regional climate velocity (i.e., the rate and direction of change of temperature isotherms). The assemblages are defined in two sub-regions of the U.S. Northeast Shelf that have heterogeneous oceanography and bathymetry using four decades of bottom trawl survey data and we explore temporal changes in distribution, spatial range extent, thermal habitat area, and biomass, within assemblages. These sub regional analyses allow the dissection of the relative roles of regional climate velocity and local physiography in shaping observed distribution shifts. We find that assemblages of species associated with shallower, warmer waters tend to shift west-southwest and to shallower waters over time, possibly towards cooler temperatures in the semi-enclosed Gulf of Maine, while species assemblages associated with relatively cooler and deeper waters shift deeper, but with little latitudinal change. Conversely, species assemblages associated with warmer and shallower water on the broad, shallow continental shelf from the Mid-Atlantic Bight to Georges Bank shift strongly northeast along latitudinal gradients with little change in depth. Shifts in depth among the southern species associated with deeper and cooler waters are more variable, although predominantly shifts are toward deeper waters. In addition, spatial expansion and contraction of species assemblages in each region corresponds to the area of suitable thermal habitat, but is inversely related to assemblage biomass. This suggests that assemblage distribution shifts in conjunction with expansion or contraction of thermal habitat acts to compress or stretch marine species assemblages, which may respectively amplify or dilute species interactions to an extent that is rarely considered. Overall, regional differences in climate change effects on the movement and extent of species assemblages hold important implications for management, mitigation, and adaptation on the U.S. Northeast Shelf. PMID- 26901437 TI - Comparison of Toxicities to Vibrio fischeri and Fish Based on Discrimination of Excess Toxicity from Baseline Level. AB - Investigations on the relationship of toxicities between species play an important role in the understanding of toxic mechanisms to environmental organisms. In this paper, the toxicity data of 949 chemicals to fish and 1470 chemicals to V. fischeri were used to investigate the modes of action (MOAs) between species. The results show that although there is a positive interspecies correlation, the relationship is poor. Analysis on the excess toxicity calculated from toxic ratios (TR) shows that many chemicals have close toxicities and share the same MOAs between the two species. Linear relationships between the toxicities and octanol/water partition coefficient (log KOW) for baseline and less inert compounds indicate that the internal critical concentrations (CBRs) approach a constant both to fish and V. fischeri for neutral hydrophobic compounds. These compounds share the same toxic mechanisms and bio-uptake processes between species. On the other hand, some hydrophilic compounds exhibit different toxic effects with greatly different log TR values between V. fischeri and fish species. These hydrophilic compounds were identified as reactive MOAs to V. fischeri, but not to fish. The interspecies correlation is improved by adding a hydrophobic descriptor into the correlation equation. This indicates that the differences in the toxic ratios between fish and V. fischeri for these hydrophilic compounds can be partly attributed to the differences of bioconcentration between the two species, rather than the differences of reactivity with the target macromolecules. These hydrophilic compounds may more easily pass through the cell membrane of V. fischeri than the gill and skin of fish, react with the target macromolecules and exhibit excess toxicity. The compounds with log KOW > 7 exhibiting very low toxicity (log TR < -1) to both species indicate that the bioconcentration potential of a chemical plays a very important role in the identification of excess toxicity and MOAs. PMID- 26901436 TI - Misexpression of cyclin D1 in embryonic germ cells promotes testicular teratoma initiation. AB - Testicular teratomas result from anomalies in embryonic germ cell development. In the 129 family of inbred mouse strains, teratomas arise during the same developmental period that male germ cells normally enter G1/G0 mitotic arrest and female germ cells initiate meiosis (the mitotic:meiotic switch). Dysregulation of this switch associates with teratoma susceptibility and involves three germ cell developmental abnormalities seemingly critical for tumor initiation: delayed G1/G0 mitotic arrest, retention of pluripotency, and misexpression of genes normally restricted to embryonic female and adult male germ cells. One misexpressed gene, cyclin D1 (Ccnd1), is a known regulator of cell cycle progression and an oncogene in many tissues. Here, we investigated whether Ccnd1 misexpression in embryonic germ cells is a determinant of teratoma susceptibility in mice. We found that CCND1 localizes to teratoma-susceptible germ cells that fail to enter G1/G0 arrest during the mitotic:meiotic switch and is the only D type cyclin misexpressed during this critical developmental time frame. We discovered that Ccnd1 deficiency in teratoma-susceptible mice significantly reduced teratoma incidence and suppressed the germ cell proliferation and pluripotency abnormalities associated with tumor initiation. Importantly, Ccnd1 expression was dispensable for somatic cell development and male germ cell specification and maturation in tumor-susceptible mice, implying that the mechanisms by which Ccnd1 deficiency reduced teratoma incidence were germ cell autonomous and specific to tumorigenesis. We conclude that misexpression of Ccnd1 in male germ cells is a key component of a larger pro-proliferative program that disrupts the mitotic:meiotic switch and predisposes 129 inbred mice to testicular teratocarcinogenesis. PMID- 26901438 TI - An experimentally validated network of nine haematopoietic transcription factors reveals mechanisms of cell state stability. AB - Transcription factor (TF) networks determine cell-type identity by establishing and maintaining lineage-specific expression profiles, yet reconstruction of mammalian regulatory network models has been hampered by a lack of comprehensive functional validation of regulatory interactions. Here, we report comprehensive ChIP-Seq, transgenic and reporter gene experimental data that have allowed us to construct an experimentally validated regulatory network model for haematopoietic stem/progenitor cells (HSPCs). Model simulation coupled with subsequent experimental validation using single cell expression profiling revealed potential mechanisms for cell state stabilisation, and also how a leukaemogenic TF fusion protein perturbs key HSPC regulators. The approach presented here should help to improve our understanding of both normal physiological and disease processes. PMID- 26901439 TI - Mitochondrial DNA copy number variation across human cancers. AB - Mutations, deletions, and changes in copy number of mitochondrial DNA (mtDNA), are observed throughout cancers. Here, we survey mtDNA copy number variation across 22 tumor types profiled by The Cancer Genome Atlas project. We observe a tendency for some cancers, especially of the bladder, breast, and kidney, to be depleted of mtDNA, relative to matched normal tissue. Analysis of genetic context reveals an association between incidence of several somatic alterations, including IDH1 mutations in gliomas, and mtDNA content. In some but not all cancer types, mtDNA content is correlated with the expression of respiratory genes, and anti-correlated to the expression of immune response and cell-cycle genes. In tandem with immunohistochemical evidence, we find that some tumors may compensate for mtDNA depletion to sustain levels of respiratory proteins. Our results highlight the extent of mtDNA copy number variation in tumors and point to related therapeutic opportunities. PMID- 26901441 TI - Linezolid is Associated with Improved Early Outcomes of Childhood Tuberculous Meningitis. AB - BACKGROUND: Linezolid serves as an important component for the treatment of drug resistant tuberculosis although there is little published data about linezolid use in children, especially in childhood tuberculous meningitis (TBM). METHODS: In this study, we retrospectively reviewed records of childhood TBM patients who started treatment between January 2012 and August 2014. A total of 86 childhood TBM patients younger than 15 years old were enrolled. Out of 86 children, 36 (41.9%) received the regimen containing linezolid. RESULTS: Thirty-two (88.9%) of 36 linezolid-treated cases had favorable outcomes, and 35 (70.0%) cases were successfully treated in the control group. The frequency of favorable outcome of linezolid group was significantly higher than that of control group (P = 0.037). In addition, compared with cases with fever clearance time of <1 week, the control group had more cases with fever clearance time of 1-4 weeks (P = 0.010) and >4 weeks (P = 0.000) than linezolid group. Furthermore, there was no significant difference in the frequency of adverse events between the two regimens (P = 0.896). In addition, the patients with adverse events were more likely to have treatment failure, the P value of which was 0.008. CONCLUSIONS: Our data demonstrate that linezolid improves early outcome of childhood TBM. The low frequency of linezolid-associated adverse effects highlights the promising prospects of its use for treatment of childhood TBM. PMID- 26901443 TI - Diagnosis and management of intramyocardial hematoma after coronary artery perforation: case studies of the Deutsches Herzzentrum Munchen. PMID- 26901444 TI - Differential incidence and type of spasm according to coronary arterial location. AB - BACKGROUND: We encounter a less provoked spasm in the left circumflex artery (LCX) by acetylcholine (ACh) testing compared with left anterior descending artery and right coronary artery (RCA) in the real world. OBJECTIVES: We investigated the clinical characteristics of provoked spasm in the LCX by ACh testing. METHODS: We retrospectively analyzed consecutive 1392 ACh testing over 20 years (1991-2011). The maximal ACh dose was 100 MUg into the left coronary artery and 80 MUg into the RCA. Positive spasm was defined as transient of more than or equal to 90% narrowing and usual chest symptoms or ischemic ECG changes. RESULTS: Positive provoked spasm was recognized in 622 patients (44.7%) including 456 RCA spasms, 448 left anterior descending artery spasms, and 176 LCX spasms. LCX-provoked spasm was significantly lower than other vessels (P<0.001). LCX provoked spasm was observed in 176 patients, of whom 113 patients (64.2%) had triple-vessel spasm, 46 patients (26.1%) had double-vessel spasm, and 17 patients (9.7%) had single-vessel spasm. More than 90% patients with LCX-provoked spasm had multiple spasms. Of 17 patients with LCX single-vessel spasm, 15 patients (88.2%) had focal spasm. CONCLUSION: Under a maximal ACh dose of 100 MUg into the left coronary artery, LCX-provoked spasm was significantly lower than other vessels and more than 90% of patients had multiple spasms. PMID- 26901440 TI - Resolving rates of mutation in the brain using single-neuron genomics. AB - Whether somatic mutations contribute functional diversity to brain cells is a long-standing question. Single-neuron genomics enables direct measurement of somatic mutation rates in human brain and promises to answer this question. A recent study (Upton et al., 2015) reported high rates of somatic LINE-1 element (L1) retrotransposition in the hippocampus and cerebral cortex that would have major implications for normal brain function, and suggested that these events preferentially impact genes important for neuronal function. We identify aspects of the single-cell sequencing approach, bioinformatic analysis, and validation methods that led to thousands of artifacts being interpreted as somatic mutation events. Our reanalysis supports a mutation frequency of approximately 0.2 events per cell, which is about fifty-fold lower than reported, confirming that L1 elements mobilize in some human neurons but indicating that L1 mosaicism is not ubiquitous. Through consideration of the challenges identified, we provide a foundation and framework for designing single-cell genomics studies. PMID- 26901446 TI - Repositioning Antitubercular 6-Nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazoles for Neglected Tropical Diseases: Structure-Activity Studies on a Preclinical Candidate for Visceral Leishmaniasis. AB - 6-Nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazole derivatives were initially studied for tuberculosis within a backup program for the clinical trial agent pretomanid (PA-824). Phenotypic screening of representative examples against kinetoplastid diseases unexpectedly led to the identification of DNDI-VL-2098 as a potential first-in-class drug candidate for visceral leishmaniasis (VL). Additional work was then conducted to delineate its essential structural features, aiming to improve solubility and safety without compromising activity against VL. While the 4-nitroimidazole portion was specifically required, several modifications to the aryloxy side chain were well-tolerated e.g., exchange of the linking oxygen for nitrogen (or piperazine), biaryl extension, and replacement of phenyl rings by pyridine. Several less lipophilic analogues displayed improved aqueous solubility, particularly at low pH, although stability toward liver microsomes was highly variable. Upon evaluation in a mouse model of acute Leishmania donovani infection, one phenylpyridine derivative (37) stood out, providing efficacy surpassing that of the original preclinical lead. PMID- 26901445 TI - High Throughput Screen for Escherichia coli Twin Arginine Translocation (Tat) Inhibitors. AB - The twin arginine translocation (Tat) pathway transports fully-folded and assembled proteins in bacteria, archaea and plant thylakoids. The Tat pathway contributes to the virulence of numerous bacterial pathogens that cause disease in humans, cattle and poultry. Thus, the Tat pathway has the potential to be a novel therapeutic target. Deciphering the Tat protein transport mechanism has been challenging since the active translocon only assembles transiently in the presence of substrate and a proton motive force. To identify inhibitors of Tat transport that could be used as biochemical tools and possibly as drug development leads, we developed a high throughput screen (HTS) to assay the effects of compounds in chemical libraries against protein export by the Escherichia coli Tat pathway. The primary screen is a live cell assay based on a fluorescent Tat substrate that becomes degraded in the cytoplasm when Tat transport is inhibited. Consequently, low fluorescence in the presence of a putative Tat inhibitor was scored as a hit. Two diverse chemical libraries were screened, yielding average Z'-factors of 0.74 and 0.44, and hit rates of ~0.5% and 0.04%, respectively. Hits were evaluated by a series of secondary screens. Electric field gradient (Deltapsi) measurements were particularly important since the bacterial Tat transport requires a Deltapsi. Seven low IC50 hits were eliminated by Deltapsi assays, suggesting ionophore activity. As Deltapsi collapse is generally toxic to animal cells and efficient membrane permeability is generally favored during the selection of library compounds, these results suggest that secondary screening of hits against electrochemical effects should be done early during hit validation. Though none of the short-listed compounds inhibited Tat transport directly, the screening and follow-up assays developed provide a roadmap to pursue Tat transport inhibitors. PMID- 26901447 TI - Importance of Orbital Optimization for Double-Hybrid Density Functionals: Application of the OO-PBE-QIDH Model for Closed- and Open-Shell Systems. AB - We assess here the reliability of orbital optimization for modern double-hybrid density functionals such as the parameter-free PBE-QIDH model. We select for that purpose a set of closed- and open-shell strongly and weakly bound systems, including some standard and widely used data sets, to show that orbital optimization improves the results with respect to standard models, notably for electronically complicated systems, and through first-order properties obtained as derivatives of the energy. PMID- 26901448 TI - Monolithically Integrated InGaAs Nanowires on 3D Structured Silicon-on-Insulator as a New Platform for Full Optical Links. AB - Monolithically integrated III-V semiconductors on a silicon-on-insulator (SOI) platform can be used as a building block for energy-efficient on-chip optical links. Epitaxial growth of III-V semiconductors on silicon, however, has been challenged by the large mismatches in lattice constants and thermal expansion coefficients between epitaxial layers and silicon substrates. Here, we demonstrate for the first time the monolithic integration of InGaAs nanowires on the SOI platform and its feasibility for photonics and optoelectronic applications. InGaAs nanowires are grown not only on a planar SOI layer but also on a 3D structured SOI layer by catalyst-free metal-organic chemical vapor deposition. The precise positioning of nanowires on 3D structures, including waveguides and gratings, reveals the versatility and practicality of the proposed platform. Photoluminescence measurements exhibit that the composition of ternary InGaAs nanowires grown on the SOI layer has wide tunability covering all telecommunication wavelengths from 1.2 to 1.8 MUm. We also show that the emission from an optically pumped single nanowire is effectively coupled and transmitted through an SOI waveguide, explicitly showing that this work lays the foundation for a new platform toward energy-efficient optical links. PMID- 26901449 TI - Could digital health applications improve the health of COPD patients? PMID- 26901450 TI - Should People with Patent Foramen Ovale Go to High Altitude? A Case Report of an Alpinist with a Patent Foramen Ovale Exposed to Extreme Altitude. PMID- 26901451 TI - Neuroanatomical correlates of tube dependency and impaired oral intake after hemispheric stroke. AB - BACKGROUND AND PURPOSE: Acute stroke patients with severely impaired oral intake are at risk of malnutrition and dehydration. Rapid identification of these patients is necessary to establish early enteral tube feeding. Whether specific lesion location predicts early tube dependency was analysed, and the neural correlates of impaired oral intake after hemispheric ischaemic stroke were assessed. METHODS: Tube dependency and functional oral intake were evaluated with a standardized comprehensive swallowing assessment within the first 48 h after magnetic resonance imaging proven first-time acute supratentorial ischaemic stroke. Voxel-based lesion symptom mapping (VLSM) was performed to compare lesion location between tube-dependent patients versus patients without tube feeding and impaired versus unimpaired oral intake. RESULTS: Out of 119 included patients 43 (36%) had impaired oral intake and 12 (10%) were tube dependent. Both tube dependency and impaired oral intake were significantly associated with a higher National Institutes of Health Stroke Scale score and larger infarct volume and these patients had worse clinical outcome at discharge. Clinical characteristics did not differ between left and right hemispheric strokes. In the VLSM analysis, mildly impaired oral intake correlated with lesions of the Rolandic operculum, the insular cortex, the superior corona radiata and to a lesser extent of the putamen, the external capsule and the superior longitudinal fascicle. Tube dependency was significantly associated with affection of the anterior insular cortex. CONCLUSIONS: Mild impairment of oral intake correlates with damage to a widespread operculo-insular swallowing network. However, specific lesions of the anterior insula lead to severe impairment and tube dependency and clinicians might consider early enteral tube feeding in these patients. PMID- 26901453 TI - Refolding of horseradish peroxidase is enhanced in presence of metal cofactors and ionic liquids. AB - The effects of various refolding additives, including metal cofactors, organic co solvents, and ionic liquids, on the refolding of horseradish peroxidase (HRP), a well-known hemoprotein containing four disulfide bonds and two different types of metal centers, a ferrous ion-containing heme group and two calcium atoms, which provide a stabilizing effect on protein structure and function, were investigated. Both metal cofactors (Ca(2+) and hemin) and ionic liquids have positive impact on the refolding of HRP. For instance, the HRP refolding yield remarkably increased by over 3-fold upon addition of hemin and calcium chloride to the refolding buffer as compared to that in the conventional urea-containing refolding buffer. Moreover, the addition of ionic liquids [EMIM][Cl] to the hemin and calcium cofactor-containing refolding buffer further enhanced the HRP refolding yield up to 80% as compared to 12% in conventional refolding buffer at relatively high initial protein concentration (5 mg/ml). These results indicated that refolding method utilizing metal cofactors and ionic liquids could enhance the yield and efficiency for metalloprotein. PMID- 26901452 TI - Hydration Properties and Solvent Effects for All-Atom Solutes in Polarizable Coarse-Grained Water. AB - Due to the importance of water in chemical and biological systems, a coarse grained representation of the solvent can greatly simplify the description of the system while retaining key thermodynamic properties of the medium. A multiscale solvation model that couples all-atom solutes and polarizable Martini coarse grained water (AAX/CGS) is developed to reproduce free energies of hydration of organic solutes. Using Monte Carlo/free energy perturbation (MC/FEP) calculations, results from multiscale and all-atom simulations are compared. Improved accuracy is obtained with the AAX/CGS approach for hydrophobic and sulfur- or halogen-containing solutes, but larger deviations are found for polar solute molecules where hydrogen bonding is featured. Furthermore, solvent effects on conformational and tautomeric equilibria of AA solutes were investigated using AA, CG, and GB/SA solvent models. It is found that the CG solvent model can reproduce well the medium effects from experiment and AA simulations; however, the GB/SA solvent model fails in some cases. A 7-30-fold reduction in computational cost is found for the present AAX/CGS multiscale simulations compared to the AA alternative. PMID- 26901454 TI - Is anti-Mullerian hormone associated with IVF outcomes in young patients with diminished ovarian reserve? AB - AIM: To investigate whether anti-Mullerian hormone (AMH) is associated with IVF cycle outcomes in young patients with diminished ovarian reserve. MATERIALS & METHODS: Retrospective study of patients <35 years of age undergoing fresh IVF who had at least two 8-cell, day-3 embryos transferred with grades 1, 1.5 or 2. Patients were subgrouped, a priori, based on serum AMH levels: <1 or >1 ng/ml and <0.5 or >0.5 ng/ml. RESULTS: In total, 1005 patients were included. Patients in the >1 ng/ml group required lesser gonadotropins compared with the <1 ng/ml and the <0.5 ng/ml group. More oocytes were retrieved from the same group compared with the latter two (p < 0.001). Despite these differences, the overall rates of clinical pregnancy, spontaneous abortion and live birth were comparable between the two groups. CONCLUSION: In patients with diminished ovarian reserve who have good quality embryos, AMH is not associated with clinical pregnancy, spontaneous miscarriage or live birth rates. PMID- 26901455 TI - Momentary symptoms of borderline personality disorder as a product of trait personality and social context. AB - Past studies identify Five Factor Model (FFM) domains that are characteristic of borderline personality disorder (BPD), including those associated with specific BPD symptoms, at a between-person level. The present study replicated these between-person associations and extended past research by assessing whether the FFM explains within-person variance in the manifestation of momentary BPD symptoms in the presence or absence of close social contact (CSC). We measured CSC and the BPD core symptoms negative affectivity, impulsivity, and interpersonal problems in 74 BPD patients and in a clinical control group of 40 depressed patients over the course of 28 days, 6 times a day. The FFM domains showed specificity in predicting momentary BPD symptoms and interacted with CSC in doing so. In particular, for BPD individuals only, momentary impulsivity and interpersonal problems were associated with higher neuroticism and extraversion and lower agreeableness, and these associations were especially strong in situations involving CSC. Negative affectivity was predicted by neuroticism for both groups of individuals, and this association was generally unaffected by CSC. Overall, experiencing CSC was positively associated with momentary BPD symptoms. Thus, both the FFM and CSC were associated with BPD patients' experience of symptoms in everyday life. Furthermore, specific FFM trait domains were particularly impactful in contexts where BPD symptoms are more likely to be manifested, providing further evidence that person-by-situation interactions are important for understanding BPD symptoms in the moment. (PsycINFO Database Record PMID- 26901456 TI - [Impact on non-adherence to farmacologic treatment on quality and sustainability of healthcare. Focus on cardiovascular diseases]. AB - Adherence to drug treatment is key to successful therapeutic intervention, especially in chronic conditions. This holds particularly true in the setting of cardiovascular diseases, because poor adherence may have serious adverse effects in terms of morbidity and mortality. Many factors may contribute to poor adherence, which can be either patient-related or dependent on the healthcare system, the physician and the environment. The identification and appropriate correction of these factors may result in both clinical and economic benefits. In this setting it is also important to assess the implications of the increasing use of generic or equivalent drugs on adherence to pharmacological therapy. This topic has recently been addressed by an important Expert Consensus Document, endorsed by the Italian Societies of Cardiovascular Disease and Prevention, which was published in the Giornale Italiano di Cardiologia. The document addressed the relevance of the problem, potential determinants and possible solutions. PMID- 26901457 TI - Cardiovascular adverse effects of targeted antiangiogenic drugs: mechanisms and management. AB - Anticancer treatment has evolved enormously over the last decade. Drugs targeting receptor tyrosine kinases, VEGFR and EGFR have changed the treatment landscape of certain cancers and have shifted the theme of anticancer therapy toward personalized care. However, these newer agents also come with unique side-effect profiles not seen with conventional chemotherapy including serious cardiovascular adverse effects. Hence, meticulous understanding of the adverse effects is crucial in maximizing clinical benefits and minimizing detrimental effects of these newer drugs. We have reviewed the cardiovascular adverse effects of anti VEGF therapy in this article. PMID- 26901458 TI - Using silver nanocluster/graphene nanocomposite to enhance photoelectrochemical activity of CdS:Mn/TiO2 for highly sensitive signal-on immunoassay. AB - A highly sensitive signal-on photoelectrochemical (PEC) immunosensor was fabricated here using CdS:Mn/TiO2 as photoelectrochemical sensing platform, and silver nanoclusters and graphene naocomposites (AgNCs-GR) as signal amplification tags. The immunosensor was constructed based on the specific sandwich immunoreaction, and the photo-to-current conversion efficiency of the isolated protein modified CdS:Mn/TiO2 matrix was improved based on the synergistic effect of AgNCs-GR. Under irradiation, the photogenerated electrons from the AgNCs at a higher conduction band edge level could be transport to the CdS:Mn/TiO2 matrix with the assistance of highly conductive graphene nanosheets, as well as recycle the trapped excitons in the defects-rich CdS:Mn/TiO2 interface. The electron transport and exciton recycle reduced the possibility of electron-hole recombination and greatly improved the photo-to-current conversion efficiency of the sensing matrix. Based on the signal enhancement, a signal-on PEC immunosensors was fabricated for the detection of carcinoembryonic antigen (CEA), a model analyte related to many malignant diseases. Under optimal conditions, the as-prepared immunosensor showed excellent analytical performance, with a wide linear range from 1.0 pg/mL to 100 ng/mL and a low limit of detection of 1.0 pg/mL. The signal-on mode provided 2.48 times higher sensitivity compared with signal-off mode. This strategy demonstrated good accuracy and high selectivity for practical sample analysis, thus may have great application prospective in the prediction and early diagnosis of diseases. PMID- 26901459 TI - Novel and simple electrochemical biosensor monitoring attomolar levels of miRNA 155 in breast cancer. AB - This work, describes for the first time, a simple biosensing design to yield an ultrasensitive electrochemical biosensor for a cancer biomarker detection, miRNA 155, with linear response down to the attomolar range. MiRNA-155 was selected for being overexpressed in breast cancer. The biosensor was assembled in two stages: (1) the immobilization of the anti-miRNA-155 that was thiol modified on an Au screen printed electrode (Au-SPE), followed by (2) blocking the areas of non specific binding with mercaptosuccinic acid. Atomic force microscopy (AFM) and electrochemical techniques including cyclic voltammetry (CV), impedance spectroscopy (EIS) and square wave voltammetry (SWV) confirmed the surface modification of these devices and their ability to hybridize successfully and stably with miRNA-155. The final biosensor provided a sensitive detection of miRNA-155 from 10 aM to 1.0 nM with a low detection limit (LOD) of 5.7 aM in real human serum samples. Good results were obtained in terms of selectivity towards breast cancer antigen CA-15.3 and bovine serum albumin (BSA). Raw fluid extracts from cell-lines of melanoma did not affect the biosensor response (no significant change of the blank), while raw extracts from breast cancer yielded a positive signal against miRNA-155. This simple and sensitive strategy is a promising alternative for simultaneous quantitative analysis of multiple miRNA in physiological fluids for biomedical research and point-of-care (POC) diagnosis. PMID- 26901460 TI - Multi-input and -output logic circuits based on bioelectrocatalysis with horseradish peroxidase and glucose oxidase immobilized in multi-responsive copolymer films on electrodes. AB - Herein, poly(N-isopropylacrylamide-co-N,N'-dimethylaminoethylmethacrylate) copolymer films were polymerized on electrode surface with a simple one-step method, and the enzyme horseradish peroxidase (HRP) was embedded in the films simultaneously, which were designated as P(NiPAAm-co-DMEM)-HRP. The films exhibited a reversible structure change with the external stimuli, such as pH, CO2, temperature and SO4(2-), causing the cyclic voltammetric (CV) response of electroactive K3Fe(CN)6 at the film electrodes to display the corresponding multi stimuli sensitive ON-OFF behavior. Based on the switchable CV property of the system and the electrochemical reduction of H2O2 catalyzed by HRP in the films and mediated by Fe(CN)6(3-) in solution, a 5-input/3-output logic gate was established. To further increase the complexity of the logic system, another enzyme glucose oxidase (GOD) was added into the films, designated as P(NiPAAm-co DMEM)-HRP-GOD. In the presence of oxygen, the oxidation of glucose in the solution was catalyzed by GOD in the films, and the produced H2O2 in situ was recognized and electrocatalytically reduced by HRP and mediated by Fe(CN)6(3-). Based on the bienzyme films, a cascaded or concatenated 4-input/3-output logic gate system was proposed. The present work combined the multi-responsive interface with bioelectrocatalysis to construct cascaded logic circuits, which might open a new avenue to develop biocomputing elements with more sophisticated functions and design novel glucose biosensors. PMID- 26901462 TI - Assessment of Wakefulness and Brain Arousal Regulation in Psychiatric Research. AB - During the last few decades, much knowledge has been gained about sleep being a heterogeneous condition with several distinct sleep stages that represent fundamentally different physiological states. The same applies for the wake state which also comprises distinct global functional states (called vigilance stages). However, various terms and concepts have been introduced describing different aspects of wakefulness, and accordingly several methods of assessment exist, e.g. sleep laboratory assessments (Multiple Sleep Latency Test, Maintenance of Wakefulness Test), questionnaires (Epworth Sleepiness Scale, Karolinska Sleepiness Scale), behavioural tasks (Psychomotor Vigilance Test) or electroencephalography (EEG)-based assessments (Alpha Attenuation Test, Karolinska Drowsiness Test). Furthermore, several theoretical concepts about the regulation of sleep and wakefulness have been put forward, and physiological correlates have been identified. Most relevant for healthy functioning is the regulation of brain arousal and the adaption of wakefulness to the environmental and situational needs so that the optimal balance between energy conservation and responsiveness can be obtained. Since one approach to the assessment of brain arousal regulation is the classification of EEG vigilance stages, a computer based algorithm (Vigilance Algorithm Leipzig) has been introduced, allowing classification of EEG vigilance stages in EEG recordings under resting conditions. The time course of EEG vigilance stages in EEGs of 15-20 min duration allows estimation of the individual arousal regulation (hyperstable, adaptive, or unstable vigilance pattern). The vigilance model of affective disorders and attention-deficit/hyperactivity disorder links a disturbed arousal regulation to the pathogenesis of psychiatric disorders and accordingly helps to explain and possibly also predict treatment effects of pharmacological and non pharmacological interventions for these conditions. PMID- 26901461 TI - Using DNA devices to track anticancer drug activity. AB - It is beneficial to develop systems that reproduce complex reactions of biological systems while maintaining control over specific factors involved in such processes. We demonstrated a DNA device for following the repair of DNA damage produced by a redox-cycling anticancer drug, beta-lapachone (beta-lap). These chips supported beta-lap-induced biological redox cycle and tracked subsequent DNA damage repair activity with redox-modified DNA monolayers on gold. We observed drug-specific changes in square wave voltammetry from these chips at therapeutic beta-lap concentrations of high statistical significance over drug free control. We also demonstrated a high correlation of this change with the specific beta-lap-induced redox cycle using rational controls. The concentration dependence of beta-lap revealed significant signal changes at levels of high clinical significance as well as sensitivity to sub-lethal levels of beta-lap. Catalase, an enzyme decomposing peroxide, was found to suppress DNA damage at a NQO1/catalase ratio found in healthy cells, but was clearly overcome at a higher NQO1/catalase ratio consistent with cancer cells. We found that it was necessary to reproduce key features of the cellular environment to observe this activity. Thus, this chip-based platform enabled tracking of beta-lap-induced DNA damage repair when biological criteria were met, providing a unique synthetic platform for uncovering activity normally confined to inside cells. PMID- 26901463 TI - Folic Acid Supplementation in Pregnancy and the Risk of Pre-Eclampsia-A Cohort Study. AB - This prospective cohort study designed to assess the effect of folic acid supplementation in pregnancy on the risk of preeclampsia (PE) took place in Ottawa, ON and Kingston, ON, Canada, from September 1, 2002 to August 31, 2008. Pregnant women, less than 20 weeks gestational age were recruited and delivered in the Ottawa region and the Kingston General Hospital. Demographic characteristics of the study participants and the patterns of supplementation of folic acid were described and occurrence of PE between women with folic acid supplementation during pregnancy and women without were compared. Multiple logistic regression was used in the estimation of the independent effect of supplementation of folic acid. Additional analyses assessing the effect of low RBC and serum folate and dose-response relationship were performed. Analyses were performed in all study participants, and then in high risk and low risk sub groups, respectively. A total of 7,669 participants were included in the final analysis. Ninety five percent of the study participants were taking folic acid supplementation in early second trimester. The rate of PE was lower in the supplementation group than in the no supplementation group, and the difference was statistically significant in high risk women. Similar patterns of associations were observed in analysis by RBC and serum folate levels and in dose response analysis. Folic acid supplementation in pregnancy may reduce PE risk in pregnant women, especially in those women with increased risk of developing PE. PMID- 26901464 TI - Comparative analyses on expression of galectins1-4, 7-10 and 12 in first trimester placenta, decidua and isolated trophoblast cells in vitro. AB - INTRODUCTION: Galectins are members of the mammalian beta-galactoside-binding proteins, which recognize Galbeta1-4GlcNAc sequences of several cell surface oligosaccharides. Plenty of galectins are already described in human tissue, especially in placenta. Here, gal-1-4, 7-10 and gal-12 were investigated systematically in trophoblast and decidua cells of first trimester placentas. MATERIAL AND METHODS: Within this study, 15 first trimester placentas after induced abortion (7th-14th week of gestation) were examined with immunohistology and immunofluorescence based on a scoring system. Moreover, isolated and cultivated trophoblast cells from the first trimester were analyzed and evaluated for expression of gal-1-4, gal-7-10 and gal-12 at mRNA and protein level with real-time RT-Polymerase chain Reaction/PCR (Taq-Man). Double immunofluorescence with trophoblast specific markers identified galectin expressing cells at the feto-maternal interface. RESULTS: We could detect immunohistochemical staining of galectins 1-4, 7-10 and 12 in first trimester placenta: all examined galectins were found in the cytotrophoblast (CTB) and syncytiotrophoblast (SCT). Gal-1, -2, -3, -4, -7, -8, -9, -10 and -12 were identified in extravillous trophoblast cells (EVT) in immunohistology and immunoflourescence. The expression of gal-1, -9, 10, and gal-12 increased after 96h incubation in vitro without stimulation at mRNA level, while gal-2, -3, -4, -7 and -8 were decreased. DISCUSSION AND CONCLUSION: This study describes a systematic analysis of the expression of gal-1 4, gal-7-10 and gal-12 in first trimester placentas and isolated trophoblast cells. Expression levels at mRNA level and the change within 96h cultivation in vitro indicate a possible influence on syncytium building of trophoblast cell on expression of galectins. Therefore, an interaction of galectins in vitro in syncytium building is possible. PMID- 26901465 TI - Novel approaches to pulmonary arterial hypertension drug discovery. AB - INTRODUCTION: Pulmonary arterial hypertension (PAH) is a rare disorder associated with abnormally elevated pulmonary pressures that, if untreated, leads to right heart failure and premature death. The goal of drug development for PAH is to develop effective therapies that halt, or ideally, reverse the obliterative vasculopathy that results in vessel loss and obstruction of blood flow to the lungs. AREAS COVERED: This review summarizes the current approach to candidate discovery in PAH and discusses the currently available drug discovery methods that should be implemented to prioritize targets and obtain a comprehensive pharmacological profile of promising compounds with well-defined mechanisms. EXPERT OPINION: To improve the successful identification of leading drug candidates, it is necessary that traditional pre-clinical studies are combined with drug screening strategies that maximize the characterization of biological activity and identify relevant off-target effects that could hinder the clinical efficacy of the compound when tested in human subjects. A successful drug discovery strategy in PAH will require collaboration of clinician scientists with medicinal chemists and pharmacologists who can identify compounds with an adequate safety profile and biological activity against relevant disease mechanisms. PMID- 26901466 TI - National Variation in Use of Immunosuppression for Kidney Transplantation: A Call for Evidence-Based Regimen Selection. AB - Immunosuppression management in kidney transplantation has evolved to include an increasingly diverse choice of medications. Although informed by patient and donor characteristics, choice of immunosuppression regimen varies widely across transplant programs. Using a novel database integrating national transplant registry and pharmacy fill records, immunosuppression use at 6-12 and 12-24 mo after transplant was evaluated for 22 453 patients transplanted in 249 U.S. programs in 2005-2010. Use of triple immunosuppression comprising tacrolimus, mycophenolic acid or azathioprine, and steroids varied widely (0-100% of patients per program), as did use of steroid-sparing regimens (0-77%), sirolimus-based regimens (0-100%) and cyclosporine-based regimens (0-78%). Use of triple therapy was more common in highly sensitized patients, women and recipients with dialysis duration >5 years. Sirolimus use appeared to diminish over the study period. Patient and donor characteristics explained only a limited amount of the observed variation in regimen use, whereas center choice explained 30-46% of the use of non-triple-therapy immunosuppression. The majority of patients who received triple-therapy (79%), cyclosporine-based (87.6%) and sirolimus-based (84.3%) regimens continued them in the second year after transplant. This population based study of immunosuppression practice demonstrates substantial variation in center practice beyond that explained by differences in patient and donor characteristics. PMID- 26901467 TI - TWEAK Regulates Muscle Functions in a Mouse Model of RNA Toxicity. AB - Myotonic dystrophy type 1 (DM1), the most common form of muscular dystrophy in adults, is caused by toxic RNAs produced from the mutant DM protein kinase (DMPK) gene. DM1 is characterized by progressive muscle wasting and weakness. Therapeutic strategies have mainly focused on targeting the toxic RNA. Previously, we found that fibroblast growth factor-inducible 14 (Fn14), the receptor for TWEAK, is induced in skeletal muscles and hearts of mouse models of RNA toxicity and that blocking TWEAK/Fn14 signaling improves muscle function and histology. Here, we studied the effect of Tweak deficiency in a RNA toxicity mouse model. The genetic deletion of Tweak in these mice significantly reduced muscle damage and improved muscle function. In contrast, administration of TWEAK in the RNA toxicity mice impaired functional outcomes and worsened muscle histopathology. These studies show that signaling via TWEAK is deleterious to muscle in RNA toxicity and support the demonstrated utility of anti-TWEAK therapeutics. PMID- 26901468 TI - Characterization of phosphorus leaching from phosphate waste rock in the Xiangxi River watershed, Three Gorges Reservoir, China. AB - Phosphate mining waste rocks dumped in the Xiangxi River (XXR) bay, which is the largest backwater zone of the Three Gorges Reservoir (TGR), are treated as Type I industry solid wastes by the Chinese government. To evaluate the potential pollution risk of phosphorus leaching from phosphate waste rocks, the phosphorus leaching behaviors of six phosphate waste rock samples with different weathering degrees under both neutral and acidic conditions were investigated using a series of column leaching experiments, following the Method 1314 standard of the US EPA. The results indicate that the phosphorus release mechanism is solubility controlled. Phosphorus release from waste rocks increases as pH decreases. The phosphorus leaching concentration and cumulative phosphorus released in acidic leaching conditions were found to be one order of magnitude greater than that in neutral leaching conditions. In addition, the phosphorus was released faster during the period when environmental pH turned from weak alkalinity to slight acidity, with this accelerated release period appearing when L/S was in the range of 0.5-2.0 mL/g. In both neutral and acidic conditions, the average values of Total Phosphorus (TP), including orthophosphates, polyphosphates and organic phosphate, leaching concentration exceed the availability by regulatory (0.5 mg/L) in the whole L/S range, suggesting that the phosphate waste rocks stacked within the XXR watershed should be considered as Type II industry solid wastes. Therefore, the phosphate waste rocks deposited within the study area should be considered as phosphorus point pollution sources, which could threaten the adjacent surface-water environment. PMID- 26901469 TI - Photocatalytic degradation and removal mechanism of ibuprofen via monoclinic BiVO4 under simulated solar light. AB - Characterized as by X-ray diffraction, scanning electron microscopy and UV-vis diffuse reflectance spectra techniques, BiVO4 photocatalyst was hydrothermally synthesized. The photocatalytic degradation mechanisms of ibuprofen (IBP) were evaluated in aqueous media via BiVO4. Results demonstrated that the prepared photocatalyst corresponded to phase-pure monoclinic scheelite BiVO4. The synthesized BiVO4 showed superior photocatalytic properties under the irradiation of visible-light. The photocatalytic degradation rate of IBP decreased with an increase in the initial IBP concentration. The degradation process followed first order kinetics model. At an IBP concentration of 10 mg L(-1), while a BiVO4 concentration of 5.0 g L(-1) with pH value of 4.5, the rate of IBP degradation was obtained as 90% after 25 min. The photocatalytic degradation of IBP was primarily accomplished via the generation of superoxide radical (O2(*-)) and hydroxyl radicals ((*)OH). During the process of degradation, part of the (*)OH was converted from the O2(*-). The direct oxidation of holes (h(+)) made a minimal contribution to the degradation of IBP. PMID- 26901471 TI - Enhancing post aerobic digestion of full-scale anaerobically digested sludge using free nitrous acid pretreatment. AB - Post aerobic digestion of anaerobically digested sludge (ADS) has been extensively applied to the wastewater treatment plants to enhance sludge reduction. However, the degradation of ADS in the post aerobic digester itself is still limited. In this work, an innovative free nitrous acid (HNO2 or FNA)-based pretreatment approach is proposed to improve full-scale ADS degradation in post aerobic digester. The post aerobic digestion was conducted by using an activated sludge to aerobically digest ADS for 4 days. Degradations of the FNA-treated (treated at 1.0 and 2.0 mg N/L for 24 h) and untreated ADSs were then determined and compared. The ADS was degraded by 26% and 32%, respectively, in the 4-day post aerobic digestion period while being pretreated at 1.0 and 2.0 mg HNO2-N/L. In comparison, only 20% of the untreated ADS was degraded. Economic analysis demonstrated that the implementation of FNA pretreatment can be economically favourable or not depending on the sludge transport and disposal cost. PMID- 26901470 TI - Bioconcentration and metabolism of ketoconazole and effects on multi-biomarkers in crucian carp (Carassius auratus). AB - The tissue distribution, bioconcentration, metabolism and biological effects of the antifungal medication ketoconazole were investigated in fish, crucian carp (Carassius auratus) were exposed to a series of nominal concentrations (0.2, 2 and 20 MUg/L) for 14 days. The ultra-high performance liquid chromatography tandem triple quadrupole mass spectroscopy (UPLC/MS/MS) analysis was used to determine the bioconcentration of ketoconazole and its metabolites in fish. The highest tissue concentration of ketoconazole was observed in the liver with the bioconcentration factor of 257.2, which is lower than the estimated BCF value. The ability of crucian carp to metabolize ketoconazole was confirmed and the results pointed out the existence of seven metabolites likely formed via oxidation of imidazole ring and the metabolic alteration of the piperazine rings. In addition, acetylcholinesterase, 7-ethoxyresorufin O-deethylase, superoxide dismutase and glutathione S-transferase changed significantly after 3, 7 and 14 days of exposure (P < 0.05), which indicated that the accumulation and metabolism of ketoconazole in fish tissues may account for the biological effects. PMID- 26901472 TI - Prediction of mixture toxicity from the hormesis of a single chemical: A case study of combinations of antibiotics and quorum-sensing inhibitors with gram negative bacteria. AB - The 50% effect level of a single chemical in the real environment is almost impossible to determine at the low exposure concentration, and the prediction of the concentration of a mixture at the 50% effect level from the concentration of a single chemical at the low effect level is even more difficult. The current literature does not address this problem. Thus, to determine solutions for this question, single/mixture chronic toxicities of sulfonamides (SAs) and quorum sensing inhibitors (QSIs) were determined using Gram-negative bacteria (Vibrio fischeri and E. coli.) and Gram-positive bacteria (B. subtilis) as the target organisms. The results showed that the joint effects of SAs and QSIs were primarily antagonistic responses. In addition, the toxicity mechanisms of mixtures of SAs and QSIs were investigated further, and the results revealed that the chronic joint effects were primarily an antagonistic response due to the QSI competing against acyl-homoserine lactones (AHL) for luxR in V. fischeri and SdiA in E. coli generated by the SAs, leading to negative effects exerted by the QSI luxR or QSI-SdiA complexes on luxI in V. fischeri or FtsZ in E. coli. This phenomenon eventually weakened the stimulatory effect caused by the SAs. Based on the mixture toxicity mechanism, the relationship between the mixture toxicity and the simulation effect was formulated. PMID- 26901473 TI - Mechanistic evaluation of polychlorinated dibenzo-p-dioxin, dibenzofuran and naphthalene isomer fingerprints in microwave pyrolysis of biomass. AB - Isomer distribution patterns of polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs) and naphthalenes (PCNs) were investigated in microwave assisted pyrolysis (MAP) products of woody biomass. The feedstocks included bark and impregnated wood. The results indicated that isomer distributions in MAP are more selective compared to those reported from wood burning and waste incineration. Favored formation of 4-MoCDF and highly selective chlorine substitution at the 2,4-position observed during MAP suggested a preferred formation pathway of PCDFs involving (chloro)phenol precursors followed by subsequent chlorination. The PCDD distribution was dominated by isomers typically formed from chlorophenol condensation at relatively low temperature. The PCN isomer distributions showed a tendency for sequential chlorination from non substituted naphthalene at successive positions. The presence of isomers such as 1-MoCDD, 4-MoCDF, 1,2,3-TriCN with low thermodynamic stability indicates that kinetic factors may be important in the MAP process. PMID- 26901474 TI - UFLC-ESI-MS/MS analysis of multiple mycotoxins in medicinal and edible Areca catechu. AB - A robust, sensitive and reliable ultra fast liquid chromatography combined with electrospray ionization tandem mass spectrometry (UFLC-ESI-MS/MS) was optimized and validated for simultaneous identification and quantification of eleven mycotoxins in medicinal and edible Areca catechu, based on one-step extraction without any further clean-up. Separation and quantification were performed in both positive and negative modes under multiple reaction monitoring (MRM) in a single run with zearalanone (ZAN) as internal standard. The chromatographic conditions and MS/MS parameters were carefully optimized. Matrix-matched calibration was recommended to reduce matrix effects and improve accuracy, showing good linearity within wide concentration ranges. Limits of quantification (LOQ) were lower than 50 MUg kg(-1), while limits of detection (LOD) were in the range of 0.1-20 MUg kg(-1). The accuracy of the developed method was validated for recoveries, ranging from 85% to 115% with relative standard deviation (RSD) <=14.87% at low level, from 75% to 119% with RSD <= 14.43% at medium level and from 61% to 120% with RSD <= 13.18% at high level, respectively. Finally, the developed multi-mycotoxin method was applied for screening of these mycotoxins in 24 commercial samples. Only aflatoxin B2 and zearalenone were found in 2 samples. This is the first report on the application of UFLC-ESI(+/-)-MS/MS for multi class mycotoxins in A. catechu. The developed method with many advantages of simple pretreatment, rapid determination and high sensitivity is a proposed candidate for large-scale detection and quantification of multiple mycotoxins in other complex matrixes. PMID- 26901475 TI - Anthropogenic signature of sediment organic matter probed by UV-Visible and fluorescence spectroscopy and the association with heavy metal enrichment. AB - Sediment organic matter (SOM) was extracted in an alkaline solution from 43 stream sediments in order to explore the anthropogenic signatures. The SOM spectroscopic characteristics including excitation-emission matrix (EEM)-parallel factor analysis (PARAFAC) were compared for five sampling site groups classified by the anthropogenic variables of land use, population density, the loadings of organics and nutrients, and metal enrichment. The conventional spectroscopic characteristics including specific UV absorbance, absorbance ratio, and humification index did not properly discriminate among the different cluster groups except in the case of metal enrichment. Of the four decomposed PARAFAC components, humic-like and tryptophan-like fluorescence responded negatively and positively, respectively, to increasing degrees of the anthropogenic variables except for land use. The anthropogenic enrichment of heavy metals was positively associated with the abundance of tryptophan-like component. In contrast, humic like component, known to be mostly responsible for metal binding, exhibited a decreasing trend corresponding with metal enrichment. These conflicting trends can be attributed to the overwhelmed effects of the coupled discharges of heavy metals and organic pollutants into sediments. Our study suggests that the PARAFAC components can be used as functional signatures to probe the anthropogenic influences on sediments. PMID- 26901476 TI - Proteomic and metabolomic analysis on the toxicological effects of As (III) and As (V) in juvenile mussel Mytilus galloprovincialis. AB - Inorganic arsenic (As) is a known pollutant including two chemical forms (arsenite (As III) and arsenate (As V)), in marine and coastal environment. Marine mussel Mytilus galloprovincialis is an important environmental monitoring species around the world. In this study, we focused on valence-specific responses of As in juvenile mussel M. galloprovincialis using a combined proteomic and metabolomic approach. Metabolic responses indicated that As (III) mainly caused disturbance in osmotic regulation in juvenile mussels. As (V) caused disturbances in both osmotic regulation and energy metabolism marked by different metabolic responses, including betaine, taurine, glucose and glycogen. Proteomic responses exhibited that As (III) had a significant negative effect on cytoskeleton and cell structure (actin and collagen alpha-6(VI) chain). As (V) affected some key enzymes involved in energy metabolism (cytosolic malate dehydrogenase, cMDH) and cell development (ornithine aminotransferase and astacin). Overall, all these results confirmed the valence-specific responses in juvenile mussels to As exposures. These findings demonstrate that a combined metabolomic and proteomic approach could provide an important insight into the toxicological effects of environmental pollutants in organisms. PMID- 26901477 TI - Statistical evaluation of biogeochemical variables affecting spatiotemporal distributions of multiple free metal ion concentrations in an urban estuary. AB - Free metal ion concentrations have been recognized as a better indicator of metal bioavailability in aquatic environments than total dissolved metal concentrations. However, our understanding of the determinants of free ion concentrations, especially in a metal mixture, is limited, due to underexplored techniques for measuring multiple free metal ions simultaneously. In this work, we performed statistical analyses on a large dataset containing repeated measurements of free ion concentrations of Cu, Zn, Pb, Ni, and Cd, the most commonly measured metals in seawater, at five inshore locations in Boston Harbor, previously collected using an in-situ equilibrium-based multi-metal free ion sampler, the 'Gellyfish'. We examined correlations among these five metals by season, and evaluated effects of 10 biogeochemical variables on free ion concentrations over time and location through multivariate regressions. We also explored potential clustering among the five metals through a principal component analysis. We found significant correlations among metals, with varying patterns over season. Our regression results suggest that instead of dissolved metals, pH, salinity, temperature and rainfall were the most significant determinants of free metal ion concentrations. For example, a one-unit decrease in pH was associated with a 2.2 (Cd) to 99 (Cu) times increase in free ion concentrations. This work is among the first to reveal key contributors to spatiotemporal variations in free ion concentrations, and demonstrated the usefulness of the Gellyfish sampler in routine sampling of free ions within metal mixtures and in generating data for statistical analyses. PMID- 26901478 TI - Roles of coagulant species and mechanisms on floc characteristics and filterability. AB - In full scale water treatment operation, the rapid filtration process, as the last step of solid-liquid separation, is largely influenced by floc characteristics. In this study, aluminium sulphate (alum) and nano-Al13 were investigated to understand the influence of coagulant species on the formation and filterability of flocs. At neutral pH, it was found that nano-Al13, a high MW polymer, showed better floc filterability than alum. This is because of the densely compacted and well-distributed size flocs from nano-Al13, even though floc sizes of alum were generally bigger. Al specie distributions of the two coagulants at different pH levels were compared by using electrospray ionization time-of-flight mass spectrometry (ESI-TOF-MS) to further elucidate the reasons for the superiority of nano-Al13 in floc filterability. Depolymerisation/re polymerisation of nano-Al13 occurred as pH changed, and Al species from nano Al13were more abundant than that from alum, especially for the high molecular weight (MW) oligomers such as Al11, Al12, Al13 and Al14. Under the charge neutralisation mechanism, higher MW Al species was found to improve coagulation performance and floc filterability. In addition, breakage resistance and regrowth ability of nano-Al13 was better than alum, at weak acid condition. Flocs formed by the charge neutralisation mechanism readily regenerated after being thoroughly broken up. The floc regrowth ability of nano-Al13 at high shear rates (200 rpm and 300 rpm) was much better than at low shear and better than any shear applied to alum., and the flocs after breakage at 200 rpm and 300 rpm also showed better filterability than other conditions. PMID- 26901479 TI - Hexachlorocyclohexane derivatives in industrial waste and samples from a contaminated riverine system. AB - Side and initial degradation products of the persistent organic pollutant hexachlorocyclohexane (HCH) were largely neglected in environmental analysis so far. However, these compounds can be indicative for biodegradation or emission sources. Thus, several samples from a contaminated riverine system in vicinity to a former HCH production site in Central Germany were analyzed. This area adjacent to the industrial megasite Bitterfeld-Wolfen is known for elevated concentrations of various organic industrial pollutants as legacy of decades of industrial activity and subsequent deposition of chemical waste and emission of waste effluents. In environmental compartments of this riverine system, several isomers of HCH related compounds were detected comprising the two lower chlorinated species tetrachlorocyclohexene (TeCCH) and pentachlorocyclohexene (PeCCH) and the higher chlorinated species heptachlorocyclohexane (HpCCH). Except for the uppermost soil of an analyzed riparian wetland, concentrations of these compounds were low. Detected isomers in sediment, water, and soil samples correlated and dominant isomers of PeCCH and HpCCH were observed in the alluvial deposits. Comparisons with industrial HCH waste revealed isomeric patterns similar to patterns found in soil samples. Therefore, the application of HpCCH as an indicator of industrial HCH pollution is suggested. PMID- 26901480 TI - Co-occurrence perspective of arsenic and fluoride in the groundwater of Diphu, Assam, Northeastern India. AB - Considerable lacunae exists in As and F(-) co-contamination investigation in the Brahmaputra and Gangetic floodplains. Therefore we selected Diphu a township in the Karbi Plateau rising from the Brahmaputra floodplains for evaluation of As and F co-occurrence, correlation with coexisting ions of the aquifer system and elucidation of potential processes for releasing As and F(-) in the groundwater. Our initial appraisal used generic plots for identification of hydro geochemical processes and major water types. Subsequently, As and F(-) co-occurrence with pH, depth, HCO3(-), SO4(2-), Ca(2+) and Fe were probed for possible correlation followed by hierarchical cluster analyses to identify key processes for co occurrence. Finally, saturation indices of groundwater minerals were calculated using MINTEQA2 to elucidate prospective As and F(-) release into groundwater. Results indicate F(-) and As presence in Ca-HCO3 rich water along with positive correlation between Ca(2+) and F(-) possibly due to limestone reserves in adjoining areas. Multivariate analyses suggest the presence of high concentrations of PO4(3-), and H4SiO4 either individually or in combination can enhance the mobility of both As and F(-) and possibly abet conditions conducive for co-contamination of aquifers. Initial release of As and F(-) from the parent rock seems driven by the anthropogenic activities while mobilization depends on chemical interactions and individual affinities of the elements. The results of speciation highlight further mobilization of As and F(-) into the groundwater which in turn require regular attention for sustainable management of scarce water resource present in the area. PMID- 26901481 TI - A five-year performance review of field-scale, slow-release permanganate candles with recommendations for second-generation improvements. AB - In 2009, we identified a TCE plume at an abandoned landfill that was located in a low permeable silty-clay aquifer. To treat the TCE, we manufactured slow-release potassium permanganate cylinders (oxidant candles) that had diameters of either 5.1 or 7.6 cm and were 91.4 cm long. In 2010, we compared two methods of candle installation by inserting equal masses of the oxidant candles (7.6-cm vs 5.1-cm dia). The 5.1-cm dia candles were inserted with direct-push rods while the 7.6-cm candles were housed in screens and lowered into 10 permanent wells. Since installation, the 7.6-cm oxidant candles have been refurbished approximately once per year by gently scraping off surface oxides. In 2012, we reported initial results; in this paper, we provide a 5-yr performance review since installation. Temporal sampling shows oxidant candles placed in wells have steadily reduced migrating TCE concentrations. Moreover, these candles still maintain an inner core of oxidant that has yet to contribute to the dissolution front and should provide several more years of service. Oxidant candles inserted by direct-push have stopped reducing TCE concentrations because a MnO2 scale developed on the outside of the candles. To counteract oxide scaling, we fabricated a second generation of oxidant candles that contain sodium hexametaphosphate. Laboratory experiments (batch and flow-through) show that these second-generation permanganate candles have better release characteristics and are less prone to oxide scaling. This improvement should reduce the need to perform maintenance on candles placed in wells and provide greater longevity for candles inserted by direct-push. PMID- 26901482 TI - The successful induction of T-cell and antibody responses by a recombinant measles virus-vectored tetravalent dengue vaccine provides partial protection against dengue-2 infection. AB - Dengue has a major impact on global public health, and the use of dengue vaccine is very limited. In this study, we evaluated the immunogenicity and protective efficacy of a dengue vaccine made from a recombinant measles virus (MV) that expresses envelope protein domain III (ED3) of dengue-1 to 4. Following immunization with the MV-vectored dengue vaccine, mice developed specific interferon-gamma and antibody responses against dengue virus and MV. Neutralizing antibodies against MV and dengue viruses were also induced, and protective levels of FRNT50 >= 10 to 4 serotypes of dengue viruses were detected in the MV-vectored dengue vaccine-immunized mice. In addition, specific interferon-gamma and antibody responses to dengue viruses were still induced by the MV-vectored dengue vaccine in mice that were pre-infected with MV. This finding suggests that the pre-existing immunity to MV did not block the initiation of immune responses. By contrast, mice that were pre-infected with dengue-3 exhibited no effect in terms of their antibody responses to MV and dengue viruses, but a dominant dengue-3 specific T-cell response was observed. After injection with dengue-2, a detectable but significantly lower viremia and a higher titer of anti-dengue-2 neutralizing antibodies were observed in MV-vectored dengue vaccine-immunized mice versus the vector control, suggesting that an anamnestic antibody response that provided partial protection against dengue-2 was elicited. Our results with regard to T-cell responses and the effect of pre-immunity to MV or dengue viruses provide clues for the future applications of an MV-vectored dengue vaccine. PMID- 26901483 TI - RAS signaling in ALK fusion lung cancer. AB - The success of ALK targeted therapy is blunted by resistance. To identify rational polytherapy strategies to improve clinical outcomes, we studied the molecular basis of ALK oncogene dependence in ALK gene rearrangement positive (ALK+) lung adenocarcinoma. We discovered that RAS-RAF-MEK-ERK signaling is the crucial downstream pathway that is required for ALK+ tumor cell survival. Upfront co-inhibition of ALK and MEK improved response and blocked resistance in preclinical ALK+ lung cancer models, providing rationale for a new treatment paradigm for ALK+ patients. PMID- 26901485 TI - Composition and Permeability of Oleate Adlayers of CdS Quantum Dots upon Dilution to Photoluminescence-Relevant Concentrations. AB - This paper describes the changes in surface chemistry that occur in oleate-capped CdS quantum dots (QDs) upon dilution from NMR-relevant concentrations (10 MUM) to photoluminescence (PL)-relevant concentrations (0.1 MUM) and the consequences these changes have on the relative probabilities of radiative and nonradiative decay of the QD exciton. Characterization of the QD surface by nuclear magnetic resonance (NMR) spectroscopy reveals that upon dilution in three solvents, C6D6, C6D12, and CDCl3, oleate ligands, in the form of cadmium oleate and Cd(x)OA(y) clusters, desorb. Changes in the ligand coverage by 30-40% do not impact the solubility of the QDs, do not have measurable influence on the absorption or PL line widths, produce small (+/-0.05), nonmonotonic changes in the relative PL quantum yield, and produce small, nonmonotonic changes the relative partitioning between band-edge and "trapped" exciton emission. Desorption of surface ligands as a result of dilution of the QDs does, however, make the QDs more redox-active with respect to a small-molecule photooxidant, benzoquinone (BQ), because less dense organic adlayers allow a greater number of BQs to permeate the ligand shell and adsorb to the QD surface. Unlike previous studies, in which the QD concentrations used for NMR characterization were more than a factor of 10 higher than those used for optical measurements, this study directly correlates the surface composition of the QDs to their photophysical properties. PMID- 26901484 TI - Early BMP, Wnt and Ca(2+)/PKC pathway activation predicts the bone forming capacity of periosteal cells in combination with calcium phosphates. AB - The development of osteoinductive calcium phosphate- (CaP) based biomaterials has, and continues to be, a major focus in the field of bone tissue engineering. However, limited insight into the spatiotemporal activation of signalling pathways has hampered the optimisation of in vivo bone formation and subsequent clinical translation. To gain further knowledge regarding the early molecular events governing bone tissue formation, we combined human periosteum derived progenitor cells with three types of clinically used CaP-scaffolds, to obtain constructs with a distinct range of bone forming capacity in vivo. Protein phosphorylation together with gene expression for key ligands and target genes were investigated 24 hours after cell seeding in vitro, and 3 and 12 days post ectopic implantation in nude mice. A computational modelling approach was used to deduce critical factors for bone formation 8 weeks post implantation. The combined Ca(2+)-mediated activation of BMP-, Wnt- and PKC signalling pathways 3 days post implantation were able to discriminate the bone forming from the non bone forming constructs. Subsequently, a mathematical model able to predict in vivo bone formation with 96% accuracy was developed. This study illustrates the importance of defining and understanding CaP-activated signalling pathways that are required and sufficient for in vivo bone formation. Furthermore, we demonstrate the reliability of mathematical modelling as a tool to analyse and deduce key factors within an empirical data set and highlight its relevance to the translation of regenerative medicine strategies. PMID- 26901487 TI - Genomic diversity of large-plaque-forming podoviruses infecting the phytopathogen Ralstonia solanacearum. AB - The genome organization, gene structure, and host range of five podoviruses that infect Ralstonia solanacearum, the causative agent of bacterial wilt disease were characterized. The phages fell into two distinctive groups based on the genome position of the RNA polymerase gene (i.e., T7-type and phiKMV-type). One-step growth experiments revealed that phiRSB2 (a T7-like phage) lysed host cells more efficiently with a shorter infection cycle (ca. 60 min corresponding to half the doubling time of the host) than phiKMV-like phages such as phiRSB1 (with an infection cycle of ca. 180 min). Co-infection experiments with phiRSB1 and phiRSB2 showed that phiRSB2 always predominated in the phage progeny independent of host strains. Most phages had wide host-ranges and the phage particles usually did not attach to the resistant strains; when occasionally some did, the phage genome was injected into the resistant strain's cytoplasm, as revealed by fluorescence microscopy with SYBR Gold-labeled phage particles. PMID- 26901491 TI - High-Flux Positively Charged Nanocomposite Nanofiltration Membranes Filled with Poly(dopamine) Modified Multiwall Carbon Nanotubes. AB - The poor dispensability of pristine carbon nanotubes in water impedes their implications in thin-film nanocomposite membranes for crucial utilities such as water purification. In this work, high-flux positively charged nanocomposite nanofiltration membranes were exploited by uniformly embedding poly(dopamine) modified multiwall carbon nanotubes (PDA-MWCNTs) in polyamide thin-film composite membranes. With poly(dopamine) modification, fine dispersion of MWCNTs in polyethyleneimine (PEI) aqueous solutions was achieved, which was interracially polymerized with trimesoyl chloride (TMC) n-hexane solutions to prepare nanocomposite membranes. The compatibility and interactions between modified MWCNTs and polyamide matrix were enhanced, attributed to the poly(dopamine) coatings on MWCNT surfaces, leading to significantly improved water permeability. At optimized conditions, pure water permeability of the PEI/PDA-MWCNTs/TMC nanofiltration membrane (M-4) was 15.32 L m(-2) h(-1) bar(-1), which was ~1.6 times increased compared with that of pristine PEI/TMC membranes. Salt rejection of M-4 to different multivalent cations decreased in the sequence ZnCl2 (93.0%) > MgCl2 (91.5%) > CuCl2 (90.5%) ~ CaCl2, which is well-suited for water softening and heavy metal ion removal. PMID- 26901486 TI - Caveolin- and clathrin-independent entry of BKPyV into primary human proximal tubule epithelial cells. AB - BK polyomavirus (BKPyV) is a human pathogen that causes polyomavirus-associated nephropathy and hemorrhagic cystitis in transplant patients. Gangliosides and caveolin proteins have previously been reported to be required for BKPyV infection in animal cell models. Recent studies from our lab and others, however, have indicated that the identity of the cells used for infection studies can greatly influence the behavior of the virus. We therefore wished to re-examine BKPyV entry in a physiologically relevant primary cell culture model, human renal proximal tubule epithelial cells. Using siRNA knockdowns, we interfered with expression of UDP-glucose ceramide glucosyltransferase (UGCG), and the endocytic vesicle coat proteins caveolin 1, caveolin 2, and clathrin heavy chain. The results demonstrate that while BKPyV does require gangliosides for efficient infection, it can enter its natural host cells via a caveolin- and clathrin independent pathway. The results emphasize the importance of studying viruses in a relevant cell culture model. PMID- 26901492 TI - Scaling Hydrodynamic Boundary Conditions of Microstructured Surfaces in the Thin Channel Limit. AB - Despite its importance in many applications and processes, a complete and unified view on how nano- and microscale asperities influence hydrodynamic interactions has yet to be reached. In particular, the effects of surface structure can be expected to become more dominant when the length scale of the asperities or textures becomes comparable to that of the fluid flow. Here we analyze the hydrodynamic drainage of a viscous silicone oil squeezed between a smooth plane and a surface decorated with hexagonal arrays of lyophilic microsized cylindrical posts. For all micropost arrays studied, the periodicity of the structures was much larger than the separation range of our measurements. In this thin channel geometry, we find the hydrodynamic drainage and separation forces for the micropost arrays cannot be fully described by existing boundary condition models for interfacial slip or a no-slip shifted plane. Instead, our results show that the influence of the microposts on the hydrodynamic drag exhibits three distinct regimes as a function of separation. For large separations, a no slip boundary condition (Reynolds theory) is observed for all surfaces until a critical (intermediate) separation, below which the position of the no-slip plane scales with surface separation until reaching a maximum, just before contact. Below this separation, a sharp decrease in the no-slip plane position then suggests that a boundary condition of a smooth surface is recovered at contact. PMID- 26901493 TI - Are baby boomer women unique? The moderating effect of birth cohort on age in substance use patterns during midlife. AB - This study examined the relationships of age to use of alcohol, marijuana, and illicit drugs, and misuse of prescription drugs, among midlife women and whether these relationships are modified by birth cohort. Structural Equation Modeling was used to analyze National Survey on Drug Use and Health data, which included 2,035 baby boomer and silent generation cohort women, ages 30 to 55. Midlife women across cohorts reduced alcohol and marijuana use, but not illicit and prescription drug misuse, as they aged. A modifying effect of birth cohort was not supported, but findings did support differential aging effects across substances. Implications are discussed. PMID- 26901494 TI - Grafting PMMA Brushes from alpha-Alumina Nanoparticles via SI-ATRP. AB - Alumina nanoparticles are widely used as nanofillers for polymer nanocomposites. Among several different polymorphs of alumina, alpha-alumina has the most desirable combination of physical properties. Hence, the attachment of polymer chains to alpha-alumina to enhance compatibility in polymeric matrixes is an important goal. However, the chemical inertness and low concentration of surface hydroxyl groups have rendered polymer modification of alpha-alumina a long standing challenge. Herein, we report that activation of alpha-alumina in concentrated or molten NaOH as well as in molten K2S2O7 increased polymer graft density up to 50%, thereby facilitating the synthesis of alpha-alumina brush particles with uniform grafting density of 0.05 nm(-2) that are readily miscible or dispersible in organic solvents or in chemically compatible polymeric hosts. PMID- 26901497 TI - Correction: Developmental Dynamics of X-Chromosome Dosage Compensation by the DCC and H4K20me1 in C. elegans. PMID- 26901495 TI - Photoactivated inhibition of cathepsin K in a 3D tumor model. AB - Collagenolytic activity of cathepsin K is important for many physiological and pathological processes including osteoclast-mediated bone degradation, macrophage function and fibroblast-mediated matrix remodeling. Here, we report application of a light-activated inhibitor for controlling activity of cathepsin K in a 3D functional imaging assay. Using prostate carcinoma cell line engineered to overexpress cathepsin K, we demonstrate the utility of the proteolytic assay in living tumor spheroids for the evaluation and quantification of the inhibitor effects on cathepsin K-mediated collagen I degradation. Importantly, we also show that utilizing the ruthenium-caged version of a potent nitrile cathepsin K inhibitor (4), cis-[Ru(bpy)2(4)2](BF4)2 (5), offers significant advantage in terms of effective concentration of the inhibitor and especially its light activated control in the 3D assay. Our results suggest that light activation provides a suitable, attractive approach for spatial and temporal control of proteolytic activity, which remains a critical, unmet need in treatment of human diseases, especially cancer. PMID- 26901496 TI - Hmga2 is dispensable for cutaneous squamous cell carcinoma. AB - Hmga2 functions as a chromatin-associated factor during development, but is not expressed in most adult tissues. Expression of Hmga2 in adult tissues has been associated with a variety of human cancers. Numerous studies have implicated Hmga2 in epithelial-to-mesenchymal transition (EMT) and cancer progression through gain of function studies, but it is unclear whether Hgma2 is necessary for EMT, tumor formation or tumor progression. We deleted Hmga2 in two mouse models of squamous cell carcinoma and found this gene to be dispensable. In fact, EMT, tumor initiation and progression all appeared to be mostly unaffected by the absence of Hmga2. Tumors lacking the ability to induce Hmga2 proceeded to initiate cutaneous spindle cell and squamous cell carcinomas with all the typical pathological and molecular hallmarks of these cancers. PMID- 26901498 TI - Genome Wide Association Studies (GWAS) Identify QTL on SSC2 and SSC17 Affecting Loin Peak Shear Force in Crossbred Commercial Pigs. AB - Of all the meat quality traits, tenderness is considered the most important with regard to eating quality and market value. In this study we have utilised genome wide association studies (GWAS) for peak shear force (PSF) of loin muscle as a measure of tenderness for 1,976 crossbred commercial pigs, genotyped for 42,721 informative SNPs using the Illumina PorcineSNP60 Beadchip. Four 1 Mb genomic regions, three on SSC2 (at 4 Mb, 5 Mb and 109 Mb) and one on SSC17 (at 20 Mb), were detected which collectively explained about 15.30% and 3.07% of the total genetic and phenotypic variance for PSF respectively. Markers ASGA0008566, ASGA0008695, DRGA0003285 and ASGA0075615 in the four regions were strongly associated with the effects. Analysis of the reference genome sequence in the region with the most important SNPs for SSC2_5 identified FRMD8, SLC25A45 and LTBP3 as potential candidate genes for meat tenderness on the basis of functional annotation of these genes. The region SSC2_109 was close to a previously reported candidate gene CAST; however, the very weak LD between DRGA0003285 (the best marker representing region SSC2_109) and CAST indicated the potential for additional genes which are distinct from, or interact with, CAST to affect meat tenderness. Limited information of known genes in regions SSC2_109 and SSC17_20 restricts further analysis. Re-sequencing of these regions for informative animals may help to resolve the molecular architecture and identify new candidate genes and causative mutations affecting this trait. These findings contribute significantly to our knowledge of the genomic regions affecting pork shear force and will potentially lead to new insights into the molecular mechanisms regulating meat tenderness. PMID- 26901499 TI - Molecular Detection of Rickettsia felis in Humans, Cats, and Cat Fleas in Bangladesh, 2013-2014. AB - High prevalence of Rickettsia felis in patients with fever of unknown origin was revealed in the north-central Bangladesh from 2012 to 2013. Subsequently, in this study, prevalence of R. felis in cats and cat fleas (Ctenocephalides felis), together with febrile patients, was studied by PCR detection of 17 kDa antigen gene and DNA sequencing. R. felis was detected in 28% (28/100) and 21% (14/68) of cat blood and cat flea samples, respectively, whereas 42% (21/50) of patients were positive for R. felis. R. felis-positive cat fleas were detected at significantly higher rate on R. felis-positive cats. The results suggested a potential role of cats and cat fleas for transmission of R. felis to humans in Bangladesh. PMID- 26901500 TI - Characterization of Liver Monocytic Myeloid-Derived Suppressor Cells and Their Role in a Murine Model of Non-Alcoholic Fatty Liver Disease. AB - Myeloid-derived suppressor cells (MDSCs) are potent suppressors of T cell immunity in tumors and inflammatory diseases. They are identified by surface expression of CD11b+Gr1+ in mice, and CD11b+Gr1+ cells accumulate in the livers of obese mice. However, many myeloid cells share these CD11b+Gr1+ markers. Accordingly, the aim of this study was to identify the authentic phenotype of MDSCs and investigate their functions in non-alcoholic fatty liver disease (NAFLD). C57BL/6J mice were divided into 2 diet groups: a normal control group and high-fat group to induce NAFLD. We demonstrated that monocytic CD11b+Gr1dim cells could be further divided into 2 populations based on side scatter (SSC) during flow cytometry. We found that SSClowCD11b+Gr1dim cells accumulated in the livers of NAFLD mice over time, and that these cells were recruited by the chemokine CCL2 and its receptor CCR2 and might expand in the liver via macrophage colony-stimulating factor stimulation. Furthermore, SSClowCD11b+Gr1dim cells had a strong suppressive ability on T cells; this effect was not observed for SSChighCD11b+Gr1dim cells, and was dependent on nitric oxide production by inducible nitric oxide synthase. Our findings demonstrate that SSClowCD11b+Gr1dim cells represent authentic MDSCs in NAFLD livers, and might serve an important negative feedback function in liver inflammation. PMID- 26901501 TI - Long-Term Predictors of Social and Leisure Activity 10 Years after Stroke. AB - BACKGROUND: Restrictions in social and leisure activity can have negative consequences for the health and well-being of stroke survivors. To support the growing number of people who are ageing with stroke, knowledge is needed about factors that influence such activity in a long-term perspective. AIM: To identify long-term predictors of the frequency of social and leisure activities 10 years after stroke. METHOD: 145 stroke survivors in Sweden were followed-up at 16 months and 10 years after a first-ever stroke. Data representing body functions, activities & participation, environmental factors and personal factors at 16 months after stroke, were used in multiple linear regression analyses to identify predictors of the activity frequency after 10 years, as assessed by the 'Community, social and civic life' sub-domain of the Frenchay Activities Index (FAI-CSC). RESULTS: At the 10-year follow-up the frequency of social and leisure activities varied considerably among the participants, with FAI-CSC scores spanning the entire score range 0-9 (mean/median 4.9/5.0). Several factors at 16 months post stroke were independently related to the long-term activity frequency. The final regression model included four significant explanatory variables. Driving a car (B = 0.999), ability to walk a few hundred meters (B = 1.698) and extent of social network (B = 1.235) had a positive effect on activity frequency, whereas an age >= 75 years had a negative effect (B = -1.657). This model explained 36.9% of the variance in the FAI-CSC (p<0.001). CONCLUSION: Stroke survivors who drive a car, have the ability to walk a few hundred meters and have a wide social network at 16 months after a first-ever stroke are more likely to have a high frequency of social and leisure activities after 10 years, indicating that supporting outdoor mobility and social anchorage of stroke survivors during rehabilitation is important to counteract long-term inactivity. PMID- 26901502 TI - Health-related quality of life and determinant factors in celiac disease. A population-based analysis of adult patients in Spain. AB - BACKGROUND: Celiac disease (CD) has a negative impact on the health-related quality of life (HRQL) of affected patients. Although HRQL and its determinants have been examined in Spanish CD patients specifically recruited in hospital settings, these aspects of CD have not been assessed among the general Spanish population. METHODS: An observational, transversal study of a non-randomized, representative sample of adult celiac patients throughout all of Spain's Autonomous Regions. Subjects were recruited through celiac patient associations. A Spanish version of the self-administered Celiac Disease-Quality of Life (CD QOL) questionnaire was used. Determinant factors of HRQL were assessed with the aid of multivariate analysis to control for confounding factors. RESULTS: We analyzed the responses provided by 1,230 patients, 1,092 (89.2%) of whom were women. The overall mean value for the CD-QOL index was 56.3 +/- 18.27 points. The dimension that obtained the most points was dysphoria, with 81.3 +/- 19.56 points, followed by limitations with 52.3 +/- 23.43 points; health problems, with 51.6 +/- 26.08 points, and inadequate treatment, with 36.1 +/- 21.18 points. Patient age and sex, along with time to diagnosis, and length of time on a gluten free diet were all independent determinant factors of certain dimensions of HRQL: women aged 31 to 40 expressed poorer HRQL while time to diagnosis and length of time on a gluten-free diet were determinant factors for better HRQL scores. CONCLUSIONS: The HRQL of adult Spanish celiac subjects is moderate, improving with the length of time patients remain on a gluten-free diet. PMID- 26901504 TI - Erratum. PMID- 26901505 TI - The comparison of high-resolution computed tomography findings in asbestosis and idiopathic pulmonary fibrosis. AB - BACKGROUND: To determine whether the HRCT findings are useful to differentiate asbestosis from idiopathic pulmonary fibrosis (IPF). METHODS: We assessed HRCT scans from patients with asbestosis (n = 96) and IPF (n = 65). The frequencies and extent of parenchymal abnormalities and the frequencies of pleural changes were evaluated by consensus of two chest radiologists. RESULTS: There was a significant difference between IPF and asbestosis in pleural changes. In addition, there were significant differences between IPF and asbestosis in several parenchymal abnormalities on CT, especially in the less advanced stage of both diseases. On multivariate analysis, HRCT features that distinguished asbestosis from IPF were subpleural lines at a distance of less than 5 mm from the inner chest wall, subpleural dots and parenchymal bands. CONCLUSIONS: There are significant differences between IPF and asbestosis in the parenchymal and pleural abnormalities on CT. PMID- 26901503 TI - High Resolution Topography of Age-Related Changes in Non-Rapid Eye Movement Sleep Electroencephalography. AB - Sleeping brain activity reflects brain anatomy and physiology. The aim of this study was to use high density (256 channel) electroencephalography (EEG) during sleep to characterize topographic changes in sleep EEG power across normal aging, with high spatial resolution. Sleep was evaluated in 92 healthy adults aged 18-65 years old using full polysomnography and high density EEG. After artifact removal, spectral power density was calculated for standard frequency bands for all channels, averaged across the NREM periods of the first 3 sleep cycles. To quantify topographic changes with age, maps were generated of the Pearson's coefficient of the correlation between power and age at each electrode. Significant correlations were determined by statistical non-parametric mapping. Absolute slow wave power declined significantly with increasing age across the entire scalp, whereas declines in theta and sigma power were significant only in frontal regions. Power in fast spindle frequencies declined significantly with increasing age frontally, whereas absolute power of slow spindle frequencies showed no significant change with age. When EEG power was normalized across the scalp, a left centro-parietal region showed significantly less age-related decline in power than the rest of the scalp. This partial preservation was particularly significant in the slow wave and sigma bands. The effect of age on sleep EEG varies substantially by region and frequency band. This non-uniformity should inform the design of future investigations of aging and sleep. This study provides normative data on the effect of age on sleep EEG topography, and provides a basis from which to explore the mechanisms of normal aging as well as neurodegenerative disorders for which age is a risk factor. PMID- 26901508 TI - When to Start Prostate Cancer Screening and When to Stop: Insights from Goteborg. PMID- 26901506 TI - Exogenous proline mediates alleviation of cadmium stress by promoting photosynthetic activity, water status and antioxidative enzymes activities of young date palm (Phoenix dactylifera L.). AB - The ability of exogenous compatible solutes, such as proline, to counteract cadmium (Cd) inhibitory effects in young date palm plants (Phoenix dactylifera L. cv Deglet Nour) was investigated. Two-year-old date palm plants were subjected for five months at different Cd stress levels (0, 10 and 30 mg CdCl2 kg(-1) soil) whether supplied or not with exogenous proline (20mM) added through the irrigation water. Different levels of Cd stress altered plant growth, gas exchanges and chlorophyll content as well as water status, but at different extent among them. In contrast, an increase of antioxidant enzymes activities of Cd-treated plants in association with high amounts of proline content, hydrogen peroxide (H2O2), thiobarbituric acid reactive substances (TBARS) and electrolyte leakage (EL) were observed. Interestingly, exogenous proline mitigated the adverse effects of Cd on young date palm. Indeed, it alleviated the oxidative damage induced by Cd accumulation and established better levels of plant growth, water status and photosynthetic activity. Moreover, proline-treated plants showed high antioxidant enzymes activities (superoxide dismutase, catalase and glutathione peroxydase) in roots and leaves as compared to Cd-treated plants. PMID- 26901507 TI - Diagnostic Accuracy and Risks of Biopsy in the Diagnosis of a Renal Mass Suspicious for Localized Renal Cell Carcinoma: Systematic Review of the Literature. AB - PURPOSE: Clinical practice varies widely on the diagnostic role of biopsy for clinically localized renal masses suspicious for renal cell carcinoma. Therefore, we performed a systematic review of the available literature to quantify the accuracy and rate of adverse events of renal mass biopsy. MATERIALS AND METHODS: MEDLINE(r), Embase(r) and the Cochrane databases were searched (January 1997 to May 2015) for relevant studies. The systematic review process established by the Agency for Healthcare Research and Quality was followed. Nondiagnostic biopsies were excluded from diagnostic accuracy calculations. RESULTS: A total of 20 studies with 2,979 patients and 3,113 biopsies were included in the study. The overall nondiagnostic rate was 14.1% with 90.4% of those undergoing surgery found to have malignancy. Repeat biopsy led to diagnosis in 80% of patients. The false positive rate was low (4.0%), histological and renal cell carcinoma subtype concordance was substantial, and Fuhrman upgrading notable (16%) from low grade (1 to 2) to high grade (3 to 4). Core biopsy was highly sensitive (97.5%, CI 96.5 98.5) and specific (96.2%, CI 90.7-100) when a diagnostic result was obtained, but most patients (~80%) did not undergo surgery after a benign biopsy. Among patients undergoing extirpation 36.7% with a negative biopsy had malignant disease on surgical pathology (negative predictive value 63.3%, CI 52.4-74.2). Direct complications included hematoma (4.9%), clinically significant pain (1.2%), gross hematuria (1.0%), pneumothorax (0.6%) and hemorrhage (0.4%). CONCLUSIONS: Diagnostic accuracy was generally high for biopsy of localized renal masses with a low complication rate, but the nondiagnostic rate and negative predictive value were concerning. Renal mass sampling should be used judiciously as further research will determine its true clinical utility. PMID- 26901509 TI - Editorial Comment. PMID- 26901512 TI - Charge transport and localization in atomically coherent quantum dot solids. AB - Epitaxial attachment of quantum dots into ordered superlattices enables the synthesis of quasi-two-dimensional materials that theoretically exhibit features such as Dirac cones and topological states, and have major potential for unprecedented optoelectronic devices. Initial studies found that disorder in these structures causes localization of electrons within a few lattice constants, and highlight the critical need for precise structural characterization and systematic assessment of the effects of disorder on transport. Here we fabricated superlattices with the quantum dots registered to within a single atomic bond length (limited by the polydispersity of the quantum dot building blocks), but missing a fraction (20%) of the epitaxial connections. Calculations of the electronic structure including the measured disorder account for the electron localization inferred from transport measurements. The calculations also show that improvement of the epitaxial connections will lead to completely delocalized electrons and may enable the observation of the remarkable properties predicted for these materials. PMID- 26901513 TI - Robust reconfigurable electromagnetic pathways within a photonic topological insulator. AB - The discovery of topological photonic states has revolutionized our understanding of electromagnetic propagation and scattering. Endowed with topological robustness, photonic edge modes are not reflected from structural imperfections and disordered regions. Here we demonstrate robust propagation along reconfigurable pathways defined by synthetic gauge fields within a topological photonic metacrystal. The flow of microwave radiation in helical edge modes following arbitrary contours of the synthetic gauge field between bianisotropic metacrystal domains is unimpeded. This is demonstrated in measurements of the spectrum of transmission and time delay along the topological domain walls. These results provide a framework for freely steering electromagnetic radiation within photonic structures. PMID- 26901514 TI - Coupling between diffusion and orientation of pentacene molecules on an organic surface. AB - The realization of efficient organic electronic devices requires the controlled preparation of molecular thin films and heterostructures. As top-down structuring methods such as lithography cannot be applied to van der Waals bound materials, surface diffusion becomes a structure-determining factor that requires microscopic understanding. Scanning probe techniques provide atomic resolution, but are limited to observations of slow movements, and therefore constrained to low temperatures. In contrast, the helium-3 spin-echo (HeSE) technique achieves spatial and time resolution on the nm and ps scale, respectively, thus enabling measurements at elevated temperatures. Here we use HeSE to unveil the intricate motion of pentacene admolecules diffusing on a chemisorbed monolayer of pentacene on Cu(110) that serves as a stable, well-ordered organic model surface. We find that pentacene moves along rails parallel and perpendicular to the surface molecules. The experimental data are explained by admolecule rotation that enables a switching between diffusion directions, which extends our molecular level understanding of diffusion in complex organic systems. PMID- 26901515 TI - Nanocrystal solids: Order and progress. PMID- 26901517 TI - New Ir Bis-Carbonyl Precursor for Water Oxidation Catalysis. AB - This paper introduces Ir(I)(CO)2(pyalc) (pyalc = (2-pyridyl)-2-propanoate) as an atom-efficient precursor for Ir-based homogeneous oxidation catalysis. This compound was chosen to simplify analysis of the water oxidation catalyst species formed by the previously reported Cp*Ir(III)(pyalc)OH water oxidation precatalyst. Here, we present a comparative study on the chemical and catalytic properties of these two precursors. Previous studies show that oxidative activation of Cp*Ir-based precursors with NaIO4 results in formation of a blue Ir(IV) species. This activation is concomitant with the loss of the placeholder Cp* ligand which oxidatively degrades to form acetic acid, iodate, and other obligatory byproducts. The activation process requires substantial amounts of primary oxidant, and the degradation products complicate analysis of the resulting Ir(IV) species. The species formed from oxidation of the Ir(CO)2(pyalc) precursor, on the other hand, lacks these degradation products (the CO ligands are easily lost upon oxidation) which allows for more detailed examination of the resulting Ir(pyalc) active species both catalytically and spectroscopically, although complete structural analysis is still elusive. Once Ir(CO)2(pyalc) is activated, the system requires acetic acid or acetate to prevent the formation of nanoparticles. Investigation of the activated bis-carbonyl complex also suggests several Ir(pyalc) isomers may exist in solution. By (1)H NMR, activated Ir(CO)2(pyalc) has fewer isomers than activated Cp*Ir complexes, allowing for advanced characterization. Future research in this direction is expected to contribute to a better structural understanding of the active species. A diol crystallization agent was needed for the structure determination of 3. PMID- 26901516 TI - Lattice engineering through nanoparticle-DNA frameworks. AB - Advances in self-assembly over the past decade have demonstrated that nano- and microscale particles can be organized into a large diversity of ordered three dimensional (3D) lattices. However, the ability to generate different desired lattice types from the same set of particles remains challenging. Here, we show that nanoparticles can be assembled into crystalline and open 3D frameworks by connecting them through designed DNA-based polyhedral frames. The geometrical shapes of the frames, combined with the DNA-assisted binding properties of their vertices, facilitate the well-defined topological connections between particles in accordance with frame geometry. With this strategy, different crystallographic lattices using the same particles can be assembled by introduction of the corresponding DNA polyhedral frames. This approach should facilitate the rational assembly of nanoscale lattices through the design of the unit cell. PMID- 26901518 TI - Shear Bond Strength of Intraoral Laser Welding and its Effect on Intrapulpal Temperature Rise in Primary Teeth: An in Vitro Study. AB - OBJECTIVE: This study compared the shear bond strength (SBS) of conventional welding (CW) and intraoral laser welding (LW) on fixed space maintainers (SMs), and investigated the intrapulpal temperature change (ITC) during LW. BACKGROUND DATA: Lasers have been used for intraoral welding. MATERIALS AND METHODS: The SBS test used 26 molar bands divided into two groups, CW and LW. Stainless steel wires were welded to the middle of the buccal and lingual aspects of all the bands, using an Nd:YAG laser for the LW group and silver solder and flux soldering media for the CW group. The samples, fixed to acrylic resin blocks, were subjected to shear testing. In the ITC test, 25 exfoliated primary second molar teeth were used to adapt molar bands. J-type thermocouple wire was positioned in the pulp chamber. ITCs were determined during Nd:YAG laser welding of stainless steel wires to the bands. Mann-Whitney U test was used to determine differences in SBS between the groups. ITCs were analyzed by paired t test. RESULTS: The SBS between groups showed significant differences (LW: 489.47 +/- 135.70; CW: 49.71 +/- 17.76; p < 0.001). The mean ITC during LW was 3.64 +/- 0.79 (min: 2.4; max: 5.10). None of the samples' ITCs exceeded the critical threshold value (5.5 degrees C). CONCLUSIONS: LW obtained a higher-strength joint than CW. ITCs during LW do not present a thermal risk to primary teeth. The intraoral use of LW for SMs in primary teeth is recommended in terms of strength and ITCs. PMID- 26901520 TI - Capturing Unknown Substrates via in Situ Formation of Tightly Bound Bisubstrate Adducts: S-Adenosyl-vinthionine as a Functional Probe for AdoMet-Dependent Methyltransferases. AB - Identifying an enzyme's substrates is essential to understand its function, yet it remains challenging. A fundamental impediment is the transient interactions between an enzyme and its substrates. In contrast, tight binding is often observed for multisubstrate-adduct inhibitors due to synergistic interactions. Extending this venerable concept to enzyme-catalyzed in situ adduct formation, unknown substrates were affinity-captured by an S-adenosyl-methionine (AdoMet, SAM)-dependent methyltransferase (MTase). Specifically, the electrophilic methyl sulfonium (alkyl donor) in AdoMet is replaced with a vinyl sulfonium (Michael acceptor) in S-adenosyl-vinthionine (AdoVin). Via an addition reaction, AdoVin and the nucleophilic substrate form a covalent bisubstrate-adduct tightly complexed with thiopurine MTase (2.1.1.67). As such, an unknown substrate was readily identified from crude cell lysates. Moreover, this approach is applicable to other systems, even if the enzyme is unknown. PMID- 26901519 TI - Global Health Diplomacy, Monitoring & Evaluation, and the Importance of Quality Assurance & Control: Findings from NIMH Project Accept (HPTN 043): A Phase III Randomized Controlled Trial of Community Mobilization, Mobile Testing, Same-Day Results, and Post-Test Support for HIV in Sub-Saharan Africa and Thailand. AB - BACKGROUND: Provision and scale-up of high quality, evidence-based services is essential for successful international HIV prevention interventions in order to generate and maintain intervention uptake, study integrity and participant trust, from both health service delivery and diplomatic perspectives. METHODS: We developed quality assurance (QAC) procedures to evaluate staff fidelity to a cluster-randomized trial of the NIMH Project Accept (HPTN 043) assessing the effectiveness of a community-based voluntary counseling and testing strategy. The intervention was comprised of three components-Mobile Voluntary Counseling and Testing (MVCT), Community Mobilization (CM) and Post-Test Support Services (PTSS). QAC procedures were based on standardized criteria, and were designed to assess both provider skills and adherence to the intervention protocol. Supervisors observed a random sample of 5% to 10% of sessions each month and evaluated staff against multiple criteria on scales of 1-5. A score of 5 indicated 100% adherence, 4 indicated 95% adherence, and 3 indicated 90% adherence. Scores below 3 were considered unsatisfactory, and protocol deviations were discussed with the respective staff. RESULTS: During the first year of the intervention, the mean scores of MVCT and CM staff across the 5 study sites were 4 (95% adherence) or greater and continued to improve over time. Mean QAC scores for the PTSS component were lower and displayed greater fluctuations. Challenges to PTSS staff were identified as coping with the wide range of activities in the PTSS component and the novelty of the PTSS process. QAC fluctuations for PTSS were also associated with new staff hires or changes in staff responsibilities. Through constant staff monitoring and support, by Year 2, QAC scores for PTSS activities had reached those of MVCT and CM. CONCLUSIONS: The implementation of a large-sale, evidence based HIV intervention requires extensive QAC to ensure implementation effectiveness. Ongoing appraisal of study staff across sites ensures consistent and high quality delivery of all intervention components, in keeping with the goals of the study protocol, while also providing a forum for corrective feedback, additional supervision and retraining of staff. QAC ensures staff fidelity to study procedures and is critical to the successful delivery of multi-site HIV prevention interventions, as well as the delivery of services scaled up in programmatic situations. PMID- 26901521 TI - Grape pomace and grape pomace extract improve insulin signaling in high-fat fructose fed rat-induced metabolic syndrome. AB - In this study the effect of diet supplementation with grape pomace (GP) and grape pomace extract (GPE) on insulin sensitive tissues (adipose, liver and muscle) was evaluated in an experimental model of metabolic syndrome (MetS). MetS was developed by giving a high-fat-fructose (HFF) diet to Wistar rats. Six weeks of HFF diet induced weight gain, which was partially attenuated by GP (1 g per kg per day) and GPE (300 mg per kg per day) supplementation. HFF diet increased systolic blood pressure, triglycerides, insulin resistance (HOMA:IR) and inflammation (c-reactive protein (CRP)). Supplementation with GP prevented SBP, triglycerides and CRP increased and partially attenuated insulin resistance. On the other hand, GPE partially reduced SBP and triglycerides and significantly prevented insulin resistance and inflammation. Also, HFF diet induced higher triglycerides content and enhanced NADPH oxidase activity in the liver. Also, HFF diet increased the epididymal adipose tissue weight, enlarged adipocyte size, and c-jun N-terminal kinase (JNK) activation, probably contributing to a pro inflammatory cytokine pattern (higher resistin) and lower adiponectin protein expression. These alterations may result in an impairment of insulin signaling cascade observed in adipose, liver and muscle tissue (IRS1, Akt, and extracellular signal-regulated kinases (ERK1/2)) from HFF rats. Supplementation with GP and to a greater extent GPE attenuated liver triglyceride content and adiposity and restored adipose, liver and muscle response to insulin. These findings show that supplementation with GP and GPE to a greater extent can counteract adiposity, inflammation, liver damage and impaired insulin signaling associated to MetS, supporting the utilization of winemaking residues in food industry/human health due to their high amount of bioactive compounds. PMID- 26901522 TI - Light-induced gradual activation of photosystem II in dark-grown Norway spruce seedlings. AB - Gymnosperms, unlike angiosperms, are able to synthesize chlorophyll and form photosystems in complete darkness. Photosystem I (PSI) formed under such conditions is fully active, but photosystem II (PSII) is present in its latent form with inactive oxygen evolving complex (OEC). In this work we have studied light-induced gradual changes in PSII function in dark-grown cotyledons of Norway spruce (Picea abies) via the measurement of chlorophyll a fluorescence rise, absorption changes at 830 nm, thermoluminescence glow curves (TL) and protein analysis. The results indicate that in dark-grown cotyledons, alternative reductants were able to act as electron donors to PSII with inactive OEC. Illumination of cotyledons for 5 min led to partial activation of PSII, which was accompanied by detectable oxygen evolution, but still a substantial number of PSII centers remained in the so called PSII-Q(B)-non-reducing form. Interestingly, even 24 h long illumination was not sufficient for the full activation of PSII centers. This was evidenced by a weak attachment of PsbP protein and the absence of PsbQ protein in PSII particles, the absence of PSII supercomplexes, the suboptimal maximum yield of PSII photochemistry, the presence of C band in TL curve and also the presence of up-shifted Q band in TL in DCMU treated cotyledons. This slow light-induced activation of PSII in dark-grown cotyledons could contribute to the prevention of PSII overexcitation before the light-induced increase in PSI/PSII ratio allows effective operation of linear electron flow. PMID- 26901523 TI - Polymorphisms in B Cell Co-Stimulatory Genes Are Associated with IgG Antibody Responses against Blood-Stage Proteins of Plasmodium vivax. AB - The development of an effective immune response can help decrease mortality from malaria and its clinical symptoms. However, this mechanism is complex and has significant inter-individual variation, most likely owing to the genetic contribution of the human host. Therefore, this study aimed to investigate the influence of polymorphisms in genes involved in the costimulation of B lymphocytes in the naturally acquired humoral immune response against proteins of the asexual stage of Plasmodium vivax. A total of 319 individuals living in an area of malaria transmission in the Brazilian Amazon were genotyped for four SNPs in the genes CD40, CD40L, BLYS and CD86. In addition, IgG antibodies against P. vivax apical membrane antigen 1 (PvAMA-1), Duffy binding protein (PvDBP) and merozoite surface protein 1 (PvMSP-119) were detected by ELISA. The SNP BLYS 871C>T was associated with the frequency of IgG responders to PvAMA-1 and PvMSP 119. The SNP CD40 -1C>T was associated with the IgG response against PvDBP, whereas IgG antibody titers against PvMSP-119 were influenced by the polymorphism CD86 +1057G>A. These data may help to elucidate the immunological aspects of vivax malaria and consequently assist in the design of malaria vaccines. PMID- 26901524 TI - A New 3D Tool for Assessing the Accuracy of Bimaxillary Surgery: The OrthoGnathicAnalyser. AB - AIM: The purpose of this study was to present and validate an innovative semi automatic approach to quantify the accuracy of the surgical outcome in relation to 3D virtual orthognathic planning among patients who underwent bimaxillary surgery. MATERIAL AND METHOD: For the validation of this new semi-automatic approach, CBCT scans of ten patients who underwent bimaxillary surgery were acquired pre-operatively. Individualized 3D virtual operation plans were made for all patients prior to surgery. During surgery, the maxillary and mandibular segments were positioned as planned by using 3D milled interocclusal wafers. Consequently, post-operative CBCT scan were acquired. The 3D rendered pre- and postoperative virtual head models were aligned by voxel-based registration upon the anterior cranial base. To calculate the discrepancies between the 3D planning and the actual surgical outcome, the 3D planned maxillary and mandibular segments were segmented and superimposed upon the postoperative maxillary and mandibular segments. The translation matrices obtained from this registration process were translated into translational and rotational discrepancies between the 3D planning and the surgical outcome, by using the newly developed tool, the OrthoGnathicAnalyser. To evaluate the reproducibility of this method, the process was performed by two independent observers multiple times. RESULTS: Low intra observer and inter-observer variations in measurement error (mean error < 0.25 mm) and high intraclass correlation coefficients (> 0.97) were found, supportive of the observer independent character of the OrthoGnathicAnalyser. The pitch of the maxilla and mandible showed the highest discrepancy between the 3D planning and the postoperative results, 2.72 degrees and 2.75 degrees respectively. CONCLUSION: This novel method provides a reproducible tool for the evaluation of bimaxillary surgery, making it possible to compare larger patient groups in an objective and time-efficient manner in order to optimize the current workflow in orthognathic surgery. PMID- 26901525 TI - Insulin-Like Growth Factors Are Expressed in the Taste System, but Do Not Maintain Adult Taste Buds. AB - Growth factors regulate cell growth and differentiation in many tissues. In the taste system, as yet unknown growth factors are produced by neurons to maintain taste buds. A number of growth factor receptors are expressed at greater levels in taste buds than in the surrounding epithelium and may be receptors for candidate factors involved in taste bud maintenance. We determined that the ligands of eight of these receptors were expressed in the E14.5 geniculate ganglion and that four of these ligands were expressed in the adult geniculate ganglion. Of these, the insulin-like growth factors (IGF1, IGF2) were expressed in the ganglion and their receptor, insulin-like growth factor receptor 1 (IGF1R), were expressed at the highest levels in taste buds. To determine whether IGF1R regulates taste bud number or structure, we conditionally eliminated IGF1R from the lingual epithelium of mice using the keratin 14 (K14) promoter (K14 Cre::Igf1rlox/lox). While K14-Cre::Igf1rlox/lox mice had significantly fewer taste buds at P30 compared with control mice (Igf1rlox/lox), this difference was not observed by P80. IGF1R removal did not affect taste bud size or cell number, and the number of phospholipase C beta2- (PLCbeta2) and carbonic anhydrase 4- (Car4) positive taste receptor cells did not differ between genotypes. Taste buds at the back of the tongue fungiform taste field were larger and contained more cells than those at the tongue tip, and these differences were diminished in K14 Cre::Igf1rlox/lox mice. The epithelium was thicker at the back versus the tip of the tongue, and this difference was also attenuated in K14-Cre::Igf1rlox/lox mice. We conclude that, although IGFs are expressed at high levels in the taste system, they likely play little or no role in maintaining adult taste bud structure. IGFs have a potential role in establishing the initial number of taste buds, and there may be limits on epithelial thickness in the absence of IGF1R signaling. PMID- 26901526 TI - Emx1 Is Required for Neocortical Area Patterning. AB - Establishing appropriate area patterning in the neocortex is a critical developmental event, and transcription factors whose expression is graded across the developing neural axes have been implicated in this process. While previous reports suggested that the transcription factor Emx1 does not contribute to neocortical area patterning, those studies were performed at perinatal ages prior to the emergence of primary areas. We therefore examined two different Emx1 deletion mouse lines once primary areas possess mature features. Following the deletion of Emx1, the frontal and motor areas were expanded while the primary visual area was reduced, and overall the areas shifted posterio-medially. This patterning phenotype was consistent between the two Emx1 deletion strategies. The present study demonstrates that Emx1 is an area patterning transcription factor and is required for the specification of the primary visual area. PMID- 26901527 TI - The Efficient Coding of Speech: Cross-Linguistic Differences. AB - Neural coding in the auditory system has been shown to obey the principle of efficient neural coding. The statistical properties of speech appear to be particularly well matched to the auditory neural code. However, only English has so far been analyzed from an efficient coding perspective. It thus remains unknown whether such an approach is able to capture differences between the sound patterns of different languages. Here, we use independent component analysis to derive information theoretically optimal, non-redundant codes (filter populations) for seven typologically distinct languages (Dutch, English, Japanese, Marathi, Polish, Spanish and Turkish) and relate the statistical properties of these filter populations to documented differences in the speech rhythms (Analysis 1) and consonant inventories (Analysis 2) of these languages. We show that consonant class membership plays a particularly important role in shaping the statistical structure of speech in different languages, suggesting that acoustic transience, a property that discriminates consonant classes from one another, is highly relevant for efficient coding. PMID- 26901528 TI - Geometry of Chemical Beam Vapor Deposition System for Efficient Combinatorial Investigations of Thin Oxide Films: Deposited Film Properties versus Precursor Flow Simulations. AB - An innovative deposition system has been developed to construct complex material thin films from single-element precursors by chemical beam vapor deposition (CBVD). It relies on well distributed punctual sources that emit individually controlled precursor beams toward the substrate under high vacuum conditions combined with well designed cryo-panel surfaces that avoid secondary precursor sources. In this configuration the impinging flows of all precursors can be calculated at any substrate point considering the controlled angular distribution of the emitted beams and the ballistic trajectory of the molecules. The flow simulation is described in details. The major advantage of the deposition system is its ability to switch between several possible controlled combinatorial configurations, in which the substrate is exposed to a wide range of flow compositions from the different precursors, and a uniform configuration, in which the substrate is exposed to a homogeneous flow, even on large substrates, with high precursor use efficiency. Agreement between calculations and depositions carried out in various system configurations and for single, binary, or ternary oxides in mass transfer limited regime confirms that the distribution of incoming precursors on the substrate follows the theoretical models. Additionally, for some selected precursors and in some selected conditions, almost 100% of the precursor impinging on the substrate is incorporated to the deposit. The results of this work confirm the potentialities of CBVD both as a research tool to investigate efficiently deposition processes and as a fabrication tool to deposit on large surfaces. PMID- 26901530 TI - Structural and functional insights into an archaeal L-asparaginase obtained through the linker-less assembly of constituent domains. Corrigendum. AB - A correction is made to Fig. 7 in the article by Tomar et al. [(2014). Acta Cryst. D70, 3187-3197]. PMID- 26901529 TI - Effect of Paternal Age on Reproductive Outcomes of Intracytoplasmic Sperm Injection. AB - The impact of paternal age on reproduction, especially using assisted reproductive technologies, has not been well studied to date. To investigate the effect of paternal age on reproductive outcomes, here we performed a retrospective analysis of 2,627 intracytoplasmic sperm injection (ICSI) cycles performed at the Reproductive Medicine Center of the Third Affiliated Hospital of Guangzhou Medical University (China) between January 2007 and May 2015. Effect of paternal age on embryo quality [number of fertilized oocytes, 2 pronucleus zygotes (2PNs), viable embryos, and high-quality embryos] was analyzed by multiple linear regression. Relationships between paternal age and pregnancy outcomes were analyzed by binary logistic regression. After adjusting for female age, no association between paternal age and the following parameters of embryo quality was observed: number of fertilized oocytes (B = -0.032; 95% CI -0.069 0.005; P = 0.088), number of 2PNs (B = -0.005; 95% CI -0.044-0.034; P = 0.806), and number of viable embryos (B = -0.025; 95% CI -0.052-0.001; P = 0.062). However, paternal age negatively influenced the number of high-quality embryos (B = -0.020; 95% CI -0.040-0.000; P = 0.045). Moreover, paternal age had no effect on pregnancy outcomes (OR for a 5-year interval), including the rates of clinical pregnancy (OR 0.919; 95% CI 0.839-1.006; P = 0.067), ongoing pregnancy (OR 0.914; 95% CI 0.833-1.003; P = 0.058), early pregnancy loss (OR 1.019; 95% CI 0.823 1.263; P = 0.861), live births (OR 0.916; 95% CI 0.833-1.007; P = 0.070), and preterm births (OR 1.061; 95% CI 0.898-1.254; P = 0.485). Therefore, increased paternal age negatively influences the number of high-quality embryos, but has no effect on pregnancy outcomes in couples undergoing ICSI cycles. However, more studies including men aged over 60 years with a longer-term follow-up are needed. PMID- 26901531 TI - The novel tumor suppressor AIRAPL regulates IGF1R proteostasis. PMID- 26901533 TI - Analysis of PEDI Normative Data Between Spain and the United States. AB - PURPOSE: To analyze the applicability of the Pediatric Evaluation of Disability Inventory (PEDI) to the Spanish population, and to assess the influence of demographic variables on the functional performance of the child. METHOD: The Spanish version of the PEDI was administered via interview representing a sample of 199 children without disability. The applicability of the PEDI was analyzed with the Welch t test and differences between the variables were analyzed using single-factor analysis of variance. RESULTS: Significant differences in overall and domain-specific performance were found between Spanish and American samples. The Spanish sample's average score was lower than the American sample. Differences in performance within the Spanish sample were found by age, sex, and rural/urban living environment. CONCLUSIONS: The normative values of the PEDI should be applied with caution in the Spanish population until further data are available; however, the PEDI remains a useful instrument for monitoring functional change. PMID- 26901532 TI - Autoantibodies against the Second Extracellular Loop of M3R Do neither Induce nor Indicate Primary Sjogren's Syndrome. AB - OBJECTIVES: Anti-muscarinic acetylcholine type-3 receptor (anti-M3R) autoantibodies have been suggested to be pathogenic for primary Sjogren's syndrome (pSS), and the second extracellular loop of M3R is suspected to carry a disease-promoting epitope. In this study, we aimed to evaluate the pathogenicity of autoantibodies against peptides derived from the second extracellular loop of M3R in mice and to determine whether those autoantibodies could be used as biomarker for pSS. METHODS: BALB/c mice were immunized with modified linear or cyclic peptides of the second extracellular loop of M3R. The function of exocrine glands was evaluated by measuring the secretion of saliva and tears. The histological evaluations were performed by using H&E staining or direct immunofluorescence staining. Autoantibodies against linear or cyclic peptides of the second extracellular loop of M3R in human and mice were determined using ELISA. RESULTS: Immunization induced mice to produce autoantibodies against the linear or cyclic peptides of the second extracellular loop of M3R, and those autoantibodies could bind onto salivary glands. However, those mice showed neither impairment in the secretion of tears or saliva nor histological abnormality in the exocrine glands. Furthermore, passive transfer of the IgG isolated from the immunized mice into healthy mice did not induced the dysfunction of the exocrine glands. The prevalence of autoantibodies against the peptides of the second extracellular loop of M3R was low in pSS patients, and it did not differ significantly from that in healthy controls. CONCLUSIONS: Our results suggest that the autoantibodies against peptides of the second extracellular loop of M3R are not pathogenic in vivo and they are not suitable as biomarkers for pSS diagnosis. PMID- 26901535 TI - Enabling 2-Wheeled Cycling for Youth With Down Syndrome. AB - PURPOSE: To study the effectiveness of cognitive orientation to daily occupational performance (CO-OP) to teach motor skills to youth with intellectual disabilities. METHODS: Six youth aged 12 to 19 years participated in this study. A multiple baseline design was employed to evaluate distance and time cycled, and a pre-post-follow-up design was used to evaluate the effect on cycling skills mastered, cycling performance, and parent satisfaction. RESULTS: At follow-up, 5 of the 6 youth rode their 2-wheeled bicycles over 100 m in their communities (range, 103-1400 m) and demonstrated improved cycling skills and parent satisfaction. CONCLUSIONS: The skills acquired by youth with Down syndrome using a CO-OP approach exceeded what has been reported in the literature. CO-OP offers a promising alternative to existing approaches for teaching 2-wheeled cycling to youth with Down syndrome. PMID- 26901534 TI - The Effect of Ankle-Foot Orthoses on Community-Based Walking in Cerebral Palsy: A Clinical Pilot Study. AB - PURPOSE: To examine the effect of ankle-foot orthoses (AFO) on walking activity in children with cerebral palsy (CP). METHODS: We used a randomized cross-over design with 11 children with bilateral CP, mean age 4.3 years. Subjects were randomized to current AFO-ON or AFO-OFF for 2 weeks and then crossed over. Walking activity (average total steps/day), intensity, and stride rate curves were collected via an ankle accelerometer. Group effects were examined with the Wilcoxon signed-rank test and within-subject effects examined for more than 1 standard deviation change. RESULTS: No significant group difference was found in average total daily step count between treatment conditions (P = .48). For the AFO-ON condition, 2 subjects (18%) increased total steps/day; 4 (36%) increased walking time; 2 (18%) had more strides at a rate of more than 30 strides/min; and 2 (18%) reached higher peak intensity. CONCLUSIONS: Clinically prescribed AFO/footwear did not consistently enhance walking activity levels or intensity. Larger studies are warranted. PMID- 26901536 TI - Distal Vibration Perception Threshold in Children Who Toe Walk. AB - PURPOSE: To compare distal vibratory perception threshold and sensation in children who toe walked (TW) and controls. METHODS: Vibration perception threshold was measured at the metacarpal and metatarsal phalangeal (MCP and MTP) joints in 11 TW and 15 age-matched controls. Mean vibratory threshold (MVT) was calculated for each site; a Pearson correlation coefficient was determined for MVT at MCP and MTP joints. Groups were compared using a Mann-Whitney U test. Parent/caregiver responses on the Short Sensory Profile (SSP) were compared using a chi test. RESULTS: MVTs at the MCP and MTP joints were highly correlated in both groups. MVT was higher in TW compared with controls at each site. Children who TW were more likely to have a total SSP score in the "probable difference" or "definite difference" categories compared with the "no difference" category. CONCLUSION: Sensation should not be overlooked in the evaluation and clinical management of toe walking. PMID- 26901537 TI - Inter- and Intrarater Reliability of the Infant Motor Profile in 3- to 18-Month Old Infants. AB - PURPOSE: To investigate inter- and intrarater reliability scoring the Infant Motor Profile (IMP). METHODS: A total of 20 infants at risk for motor developmental delay were assessed using the IMP. Six infants were born at term (gestational age: 38-42 weeks), and 14 infants were preterm (gestational age: 24 35 weeks). Videos were analyzed twice with an interval of 1 month by 4 assessors after 2 days of IMP training. RESULTS: Spearman rank scores demonstrated strong interrater and intrarater reliability for total IMP scores (inter: r = 0.80-0.96; intra: r = 0.85-0.97) and the domain of performance (r = 0.95-0.99). Reliability for the domains of variation, variability, and fluency was satisfactory (inter: r = 0.15-0.85; intra: r = 0.30-0.92). The weakest agreement was found in the domain of symmetry (inter: r = 0.20-0.69; intra: r = 0.33-0.65). CONCLUSION: Therapists naive to the IMP demonstrate good intra and interrater reliability (after 2 days of training) for most domains with the exception of symmetry. PMID- 26901538 TI - Vestibular Assessments in Children With Global Developmental Delay: An Exploratory Study. AB - PURPOSE: To compare results of 3 clinical vestibular tests between children with global developmental delay (GDD) and children with typical development (TD) and investigate the test-retest reliability. METHODS: Twenty children with GDD (aged 4.1-12.1 years) and 11 age-matched controls with TD participated. Participants with GDD underwent 2 sessions of testing. Each session consisted of the Clinical Test of Sensory Interaction and Balance (CTSIB), Dynamic Visual Acuity (DVA) test, and the modified Emory Clinical Vestibular Chair Test (m-ECVCT). RESULTS: Up to 33% of the children with GDD had abnormal DVA scores. m-ECVCT results of children with GDD demonstrated larger variance than children with TD. The CTSIB score was significantly reduced in the group with GDD. The test-retest reliability varied, with good reliability for the m-ECVCT and CTSIB, and fair reliability for the DVA. CONCLUSIONS: Findings suggest vestibular involvement in children in GDD. The clinical tests demonstrated moderate test-retest reliability. PMID- 26901539 TI - Introduction of a New Locking Nail for Treatment of Intraarticular Calcaneal Fractures. AB - OBJECTIVES: To reduce the complication rate associated with open reduction and internal fixation of displaced intraarticular calcaneal fractures through extensile approaches, a locking nail system (C-Nail) was developed for internal fixation. DESIGN: Prospective case-control study. SETTING: Two level I trauma centers (university hospital) and 1 large regional hospital in the Czech Republic and Germany. PATIENTS: One hundred three patients (89 male and 14 female; mean age, 45.6 years) with 106 calcaneal fractures were treated between February 2011 and October 2013. INTERVENTION: In all 106 cases, the stainless steel C-Nail with a length of 65 mm, a diameter of 8 mm, and 7 locking options was used for internal fixation. Previous reduction of the posterior facet was performed in 15 cases percutaneously, assisted by arthroscopy and fluoroscopy, and in 91 cases by a sinus tarsi approach. The reduced joint surface was fixed by 1 or 2 compression screws. All other fragments were fixed after reduction and temporary K-wire fixation with the C-Nail introduced percutaneously through the tuberosity and 5 to 6 interlocking screws. The latter were introduced into the sustentacular, the tuberosity, and the anterior process fragments with an aiming device consisting of 3 arms. MAIN OUTCOME MEASURES: Patients were assessed for complications, restoration of Bohler angle, posterior facet reduction with postoperative computed tomography, and weight-bearing radiographs at 6 months. Functional outcome was assessed using the American Orthopaedic Foot & Ankle Society (AOFAS) ankle/hindfoot scale after 6 and 12 months for all patients. RESULTS: Wound edge necrosis was seen in 2 cases (1.9%), and soft tissue infection was observed in 1 case (0.9%). Bohler angle improved from 7.3 degree preoperatively to 28.7 degree at 6 months. The posterior facet step-off was reduced from 5.3 mm preoperatively to 0.7 mm postoperatively. The average AOFAS score averaged 89.5 at 6-month and 92.6 at 12-month follow-up. CONCLUSIONS: The C-Nail is a new locking system for treatment of displaced intraarticular calcaneal fractures combining a primary stability with reduced soft tissue complications. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence. PMID- 26901541 TI - Critical Care Medicine After the 2014-2015 Ebola Outbreak: Are We Ready If It Happens Again? PMID- 26901540 TI - Progressive Injury in Chronic Multiple Sclerosis Lesions Is Gender-Specific: A DTI Study. AB - OBJECTIVE: To evaluate the longitudinal integrity of white matter tracts in patients with relapsing remitting multiple sclerosis (RRMS) as determined by changes in diffusivity indices of lesional and non-lesional white matter in the optic radiation over 12 months. METHODS: The optic radiation (OR) was identified in sixty RRMS patients using probabilistic tractography. MS lesions were segmented on FLAIR T2 images and a lesion mask was intersected with the co registered OR. Lesions within the OR were identified in 39 patients. Voxel-based analysis of axial diffusivity (AD) and radial diffusivity (RD) within OR lesions and non-lesional normal appearing white matter (NAWM) was performed at baseline and 12 months in 34 patients (five patients excluded due to new OR lesions). RESULTS: Both RD and AD demonstrated much higher values within the lesions compared with non-lesional NAWM. There was a significant (p<0.001) increase of lesional AD and RD during the follow-up period. This increase, however, was driven almost entirely by the male cohort, in which a significantly greater change in both AD (M-2.7%, F-0.9%) and RD (M-4.6%, F-0.7%) was observed during the follow-up period. Non-lesional NAWM also demonstrated an increase in both AD and RD, albeit on a much lesser scale (1.0% and 0.6% respectively). In contradistinction to lesions, the diffusivity change in non-lesional NAWM was similar between sexes. CONCLUSIONS: The evolution of AD and RD in chronic MS lesions over 12 months suggests ongoing inflammatory demyelinating activity accompanied by axonal loss. In addition, our findings are consistent with the recently observed trend of more rapid clinical progression in males and establish a potential in vivo biomarker of gender dichotomy by demonstrating a significantly faster rate of microstructural change in the chronic lesions of male patients with MS. PMID- 26901542 TI - Epidemiology of Massive Transfusion: A Binational Study From Sweden and Denmark. AB - OBJECTIVE: There is an increasing focus on massive transfusion, but there is a paucity of comprehensive descriptions of the massively transfused patients and their outcomes. The objective of this study is to describe the incidence rate of massive transfusion, patient characteristics, and the mortality of massively transfused patients. DESIGN: Descriptive cohort study. SETTING: Nationwide study with data from Sweden and Denmark. PATIENTS: The study was based on the Scandinavian Donations and Transfusions database, including all patients receiving 10 or more red cell concentrate transfusions in Sweden from 1987 and in Denmark from 1996. A total of 92,057 patients were included. Patients were followed until the end of 2012. MEASUREMENTS AND MAIN RESULTS: Descriptive statistics were used to characterize the patients and indications. Post transfusion mortality was expressed as crude 30-day mortality and as long-term mortality using the Kaplan-Meier method and using standardized mortality ratios. The incidence of massive transfusion was higher in Denmark (4.5 per 10,000) than in Sweden (2.5 per 10,000). The most common indication for massive transfusion was major surgery (61.2%) followed by trauma (15.4%). Massive transfusion due to obstetrical bleeding constituted only 1.8%. The overall 5-year mortality was very high (54.6%), however with large differences between indication groups, ranging from 91.1% among those transfused for a malignant disease without surgery to 1.7% among patients transfused for obstetrical bleeding. The early standardized mortality ratios were high and decreased thereafter, but remained elevated throughout the time period. CONCLUSIONS: This large-scale study based on nationwide data from Sweden and Denmark describes the complete range of massive transfusion. We report a nonnegligible incidence and both a high absolute mortality and high standardized mortality ratio. The general pattern was similar for Sweden and Denmark, and we believe that similar patterns may be found in other high-resource countries. The study provides a relevant background for clinicians and researchers for designing future studies in this field. PMID- 26901543 TI - Severity Scores in Emergency Department Patients With Presumed Infection: A Prospective Validation Study. AB - OBJECTIVES: The objectives of this study were to 1) validate a number of severity of illness scores in a large cohort of emergency department patients admitted with presumed infection and 2) compare the performance of scores in patient subgroups with increasing mortality: infection without systemic inflammatory response syndrome, sepsis, severe sepsis, and septic shock. DESIGN: Prospective, observational study. SETTING: Adult emergency department in a metropolitan tertiary, university-affiliated hospital. PATIENTS: Emergency department patients admitted with presumed infection. INTERVENTIONS: None. METHODS: Consecutive emergency department patients admitted with presumed infection were identified over 160 weeks in two periods between 2007 and 2011. Clinical and laboratory data sufficient to calculate Mortality in Emergency Department Sepsis score, Acute Physiology and Chronic Health Evaluation II, Simplified Acute Physiology Score II, Sequential Organ Failure Assessment, and the Severe Sepsis Score were entered into a database. Model discrimination was quantified using area under the receiver operating curve. Calibration was assessed using visual plots, Hosmer Lemeshow statistics, and linear regressions of observed and predicted values. MEASUREMENTS AND MAIN RESULTS: A total of 8,871 patients were enrolled with 30 day mortality of 3.7%. Area under the receiver operating curve values for the entire cohort were: Mortality in Emergency Department Sepsis score of 0.92, Simplified Acute Physiology Score II and Acute Physiology and Chronic Health Evaluation II scores of 0.90, Sequential Organ Failure Assessment score of 0.86, and Severe Sepsis Score of 0.82. Discrimination decreased in subgroups with greater mortality for each score. All scores overestimated mortality, but closest concordance between predicted and observed mortality was seen with Mortality in Emergency Department Sepsis score. CONCLUSIONS: The decrease in area under the receiver operating curve seen in subgroups with increasing mortality may explain some variation in results seen in previous validation studies. Scores developed in intensive care settings overestimated mortality in the emergency department. Our results underscore the importance of employing predictive models developed in similar patient populations. The Mortality in Emergency Department Sepsis score outperformed more complex predictive models and would be the most appropriate scoring system for use in similar emergency department populations with a wide spectrum of mortality risk. PMID- 26901545 TI - Implementation of Evidence-Based Critical Care Practices: A Sound Strategy, but Not for the Faint of Heart. PMID- 26901546 TI - Patients With Massive Transfusion: Who Are You? PMID- 26901544 TI - Development of Process Control Methodology for Tracking the Quality and Safety of Pain, Agitation, and Sedation Management in Critical Care Units. AB - OBJECTIVE: To develop sedation, pain, and agitation quality measures using process control methodology and evaluate their properties in clinical practice. DESIGN: A Sedation Quality Assessment Tool was developed and validated to capture data for 12-hour periods of nursing care. Domains included pain/discomfort and sedation-agitation behaviors; sedative, analgesic, and neuromuscular blocking drug administration; ventilation status; and conditions potentially justifying deep sedation. Predefined sedation-related adverse events were recorded daily. Using an iterative process, algorithms were developed to describe the proportion of care periods with poor limb relaxation, poor ventilator synchronization, unnecessary deep sedation, agitation, and an overall optimum sedation metric. Proportion charts described processes over time (2 monthly intervals) for each ICU. The numbers of patients treated between sedation-related adverse events were described with G charts. Automated algorithms generated charts for 12 months of sequential data. Mean values for each process were calculated, and variation within and between ICUs explored qualitatively. SETTING: Eight Scottish ICUs over a 12-month period. PATIENTS: Mechanically ventilated patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The Sedation Quality Assessment Tool agitation-sedation domains correlated with the Richmond Sedation Agitation Scale score (Spearman rho = 0.75) and were reliable in clinician-clinician (weighted kappa; kappa = 0.66) and clinician-researcher (kappa = 0.82) comparisons. The limb movement domain had fair correlation with Behavioral Pain Scale (rho = 0.24) and was reliable in clinician-clinician (kappa = 0.58) and clinician-researcher (kappa = 0.45) comparisons. Ventilator synchronization correlated with Behavioral Pain Scale (rho = 0.54), and reliability in clinician-clinician (kappa = 0.29) and clinician-researcher (kappa = 0.42) comparisons was fair-moderate. Eight hundred twenty-five patients were enrolled (range, 59-235 across ICUs), providing 12,385 care periods for evaluation (range 655-3,481 across ICUs). The mean proportion of care periods with each quality metric varied between ICUs: excessive sedation 12-38%; agitation 4-17%; poor relaxation 13-21%; poor ventilator synchronization 8-17%; and overall optimum sedation 45-70%. Mean adverse event intervals ranged from 1.5 to 10.3 patients treated. The quality measures appeared relatively stable during the observation period. CONCLUSIONS: Process control methodology can be used to simultaneously monitor multiple aspects of pain-sedation-agitation management within ICUs. Variation within and between ICUs could be used as triggers to explore practice variation, improve quality, and monitor this over time. PMID- 26901547 TI - Massive Transfusion: An Issue for Us All. PMID- 26901548 TI - Toward a Nuanced Understanding of the Role of Infection in Readmissions After Sepsis. PMID- 26901549 TI - System-Level Changes for Improving Survival From Cardiac Arrest. PMID- 26901550 TI - Iron Use in Critically Ill Patients: No More Stress? PMID- 26901551 TI - Keeping Score of Severity Scores: Taking the Next Step. PMID- 26901552 TI - Oxygen: Providing Too Much of a Good Thing? PMID- 26901553 TI - Understanding Variability in Palliative Care Utilization for Primary Intracranial Hemorrhage in the United States. PMID- 26901554 TI - Early Identification of Subsyndromal Delirium in the Critically Ill: Don't Let the Delirium Rise! PMID- 26901555 TI - Delirium in Preschool Children: Diagnostic Challenge, Piece of Cake, or Both? PMID- 26901556 TI - Back to the Present-Does Tracheostomy Technique Affect Long-Term Complications? PMID- 26901557 TI - Molecular Turbocharging Stem Cells to Improve Treatment of Experimental Spinal Cord Injury. PMID- 26901558 TI - Hypothermia as a Positive Inotropic Drug. PMID- 26901559 TI - A Framework for the Development and Interpretation of Different Sepsis Definitions and Clinical Criteria. AB - Although sepsis was described more than 2,000 years ago, and clinicians still struggle to define it, there is no "gold standard," and multiple competing approaches and terms exist. Challenges include the ever-changing knowledge base that informs our understanding of sepsis, competing views on which aspects of any potential definition are most important, and the tendency of most potential criteria to be distributed in at-risk populations in such a way as to hinder separation into discrete sets of patients. We propose that the development and evaluation of any definition or diagnostic criteria should follow four steps: 1) define the epistemologic underpinning, 2) agree on all relevant terms used to frame the exercise, 3) state the intended purpose for any proposed set of criteria, and 4) adopt a scientific approach to inform on their usefulness with regard to the intended purpose. Usefulness can be measured across six domains: 1) reliability (stability of criteria during retesting, between raters, over time, and across settings), 2) content validity (similar to face validity), 3) construct validity (whether criteria measure what they purport to measure), 4) criterion validity (how new criteria fare compared to standards), 5) measurement burden (cost, safety, and complexity), and 6) timeliness (whether criteria are available concurrent with care decisions). The relative importance of these domains of usefulness depends on the intended purpose, of which there are four broad categories: 1) clinical care, 2) research, 3) surveillance, and 4) quality improvement and audit. This proposed methodologic framework is intended to aid understanding of the strengths and weaknesses of different approaches, provide a mechanism for explaining differences in epidemiologic estimates generated by different approaches, and guide the development of future definitions and diagnostic criteria. PMID- 26901561 TI - Could Lactate Become a Biomarker of Hypoxia and a Target of Resuscitation in Sepsis? PMID- 26901560 TI - Application of a Framework to Assess the Usefulness of Alternative Sepsis Criteria. AB - The current definition of sepsis is life-threatening, acute organ dysfunction secondary to a dysregulated host response to infection. Criteria to operationalize this definition can be judged by six domains of usefulness (reliability, content, construct and criterion validity, measurement burden, and timeliness). The relative importance of these six domains depends on the intended purpose for the criteria (clinical care, basic and clinical research, surveillance, or quality improvement [QI] and audit). For example, criteria for clinical care should have high content and construct validity, timeliness, and low measurement burden to facilitate prompt care. Criteria for surveillance or QI/audit place greater emphasis on reliability across individuals and sites and lower emphasis on timeliness. Criteria for clinical trials require timeliness to ensure prompt enrollment and reasonable reliability but can tolerate high measurement burden. Basic research also tolerates high measurement burden and may not need stability over time. In an illustrative case study, we compared examples of criteria designed for clinical care, surveillance and QI/audit among 396,241 patients admitted to 12 academic and community hospitals in an integrated health system. Case rates differed four-fold and mortality three-fold. Predictably, clinical care criteria, which emphasized timeliness and low burden and therefore used vital signs and routine laboratory tests, had the greater case identification with lowest mortality. QI/audit criteria, which emphasized reliability and criterion validity, used discharge information and had the lowest case identification with highest mortality. Using this framework to identify the purpose and apply domains of usefulness can help with the evaluation of existing sepsis diagnostic criteria and provide a roadmap for future work. PMID- 26901562 TI - The authors reply. PMID- 26901563 TI - Why Did I Stop? Barriers and Facilitators to Uptake and Adherence to ART in Option B+ HIV Care in Lilongwe, Malawi. AB - Causes for loss-to-follow-up, including early refusals of and stopping antiretroviral therapy (ART), in Malawi's Option B+ program are poorly understood. This study examines the main barriers and facilitators to uptake and adherence to ART under Option B+. In depth interviews were conducted with HIV infected women who were pregnant or postpartum in Lilongwe, Malawi (N = 65). Study participants included women who refused ART initiation (N = 10), initiated ART and then stopped (N = 26), and those who initiated ART and remained on treatment (N = 29). The barriers to ART initiation were varied and included concerns about partner support, feeling healthy, and needing time to think. The main reasons for stopping ART included side effects and lack of partner support. A substantial number of women started ART after initially refusing or stopping ART. There were several facilitators for re-starting ART, including encouragement from community health workers, side effects subsiding, decline in health, change in partner, and fear of future sickness. Amongst those who remained on ART, desire to prevent transmission and improve health were the most influential facilitators. Reasons for refusing and stopping ART were varied. ART-related side effects and feeling healthy were common barriers to ART initiation and adherence. Providing consistent pre-ART counseling, early support for patients experiencing side effects, and targeted efforts to bring women who stop treatment back into care may improve long term health outcomes. PMID- 26901564 TI - Characterization and Predictive Value of Near Infrared 2-Deoxyglucose Optical Imaging in Severe Acute Pancreatitis. AB - BACKGROUND: Studying the uptake of 2-deoxy glucose (2-DG) analogs such as 2-Deoxy 2-[18F] fluoroglucose (FDG) is a common approach to identify and monitor malignancies and more recently chronic inflammation. While pancreatitis is a common cause for false positive results in human studies on pancreatic cancer using FDG, the relevance of these findings to acute pancreatitis (AP) is unknown. FDG has a short half-life. Thus, with an aim to accurately characterize the metabolic demand of the pancreas during AP in real-time, we studied the uptake of the non-radioactive, near infrared fluorescence labelled 2-deoxyglucose analog, IRDye(r) 800CW 2-DG probe (NIR 2-DG; Li-Cor) during mild and severe biliary AP. METHODS: Wistar rats (300 g; 8-12/group) were administered NIR 2-DG (10 nM; I.V.). Mild and severe biliary AP were respectively induced by biliopancreatic duct ligation (DL) alone or along with infusing glyceryl trilinoleate (GTL; 50 MUL/100 g) within 10 minutes of giving NIR 2-DG. Controls (CON) only received NIR 2-DG. Imaging was done every 5-10 minutes over 3 hrs. Average Radiant Efficiency [p/s/cm2/sr]/[MUW/cm2] was measured over the pancreas using the IVIS 200 in-vivo imaging system (PerkinElmer) using the Living Image(r) software and verified in ex vivo pancreata. Blood amylase, lipase and pancreatic edema, necrosis were measured over the course of AP. RESULTS: NIR 2-DG uptake over the first hour was not influenced by AP induction. However, while the signal declined in controls and rats with mild AP, there was significantly higher retention of NIR 2-DG in the pancreas after 1 hour in those with GTL pancreatitis. The increase was > 3 fold over controls in the GTL group and was verified to be in the pancreas ex vivo. In vitro, pancreatic acini exposed to GTL had a similar increase in NIR 2 DG uptake which was followed by progressively worse acinar necrosis. Greater retention of NIR 2-DG in vivo was associated with worse pancreatic necrosis, reduced ATP concentrations and mortality, which were not predicted by the blood parameters. CONCLUSION: In-vivo fluorescent imaging of a non-radioactive near infrared 2-DG optical probe can predict the AP severity early during the disease. PMID- 26901565 TI - Evaluation of Costimulatory Molecules in Peripheral Blood Lymphocytes of Canine Patients with Histiocytic Sarcoma. AB - Histiocytic sarcoma is a rapidly progressive and fatal neoplastic disease in dogs. It is unclear whether costimulatory molecules, including CD28, cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), and programmed death-1 (PD-1), are expressed on peripheral blood lymphocytes (PBLs) of canine patients with histiocytic sarcoma. The objective of this study was to evaluate the expression of CD28, CTLA-4, and PD-1 molecules on PBLs of patients with histiocytic sarcoma, patients with other tumors, and healthy controls. Twenty-six dogs were included in the study, with eight, ten, and eight dogs in the histiocytic sarcoma, other tumor, and healthy control groups, respectively. PBLs and serum were prospectively obtained from patients diagnosed histopathologically with histiocytic sarcoma, other tumors and healthy controls. The surface expression of CTLA-4, CD28, and PD-1 on T lymphocytes was examined using flow cytometric analysis. Serum samples were frozen at -30 degrees C until serum interferon-gamma (IFN-gamma) was measured by enzyme-linked immunosorbent assay. The expression level of CTLA-4 on CD4+ lymphocytes was significantly higher in the histiocytic sarcoma group than in the control group. The expression of CTLA-4 on CD8+ lymphocytes was significantly higher in the histiocytic sarcoma group than in the other two groups. In addition, the expression of PD-1 on CD8+ lymphocytes was significantly higher in the histiocytic sarcoma group than in the control group. However, no significant differences in CD28 expressions and serum IFN-gamma levels were observed. The present results provided evidence showing that the expression levels of CTLA-4 on both CD4+ and CD8+ lymphocytes and PD-1 on CD8+ lymphocytes in peripheral blood obtained from dogs with histiocytic sarcoma were upregulated. The overexpressions of CTLA 4 and PD-1 suggested that antitumor immunity may be suppressed in dogs with histiocytic sarcoma. PMID- 26901568 TI - Avoiding Missed Opportunities by Analyzing the Sensitivity of Our Decisions. AB - Drug discovery is a multiparameter optimization process in which the goal of a project is to identify compounds that meet multiple property criteria required to achieve a therapeutic objective. However, once a profile of property criteria has been chosen, the impact of these criteria on the decisions made regarding progression of compounds or chemical series should be carefully considered. In some cases the decision is very sensitive to a specific property criterion, and such a criterion may artificially distort the direction of the project; any uncertainty in the "correct" value or the importance of this criterion may lead to valuable opportunities being missed. In this paper, we describe a method for analyzing the sensitivity of the prioritization of compounds to a multiparameter profile of property criteria. We show how the results can be easily interpreted and illustrate how this analysis can highlight new avenues for exploration. PMID- 26901567 TI - Ultrafast Photochemistry of Copper(II) Monochlorocomplexes in Methanol and Acetonitrile by Broadband Deep-UV-to-Near-IR Femtosecond Transient Absorption Spectroscopy. AB - Photochemistry of copper(II) monochlorocomplexes in methanol and acetonitrile solutions is studied by UV-pump/broadband deep-UV-to-near-IR probe femtosecond transient absorption spectroscopy. Upon 255 and 266 nm excitation, the complexes in acetonitrile and methanol, respectively, are promoted to the excited ligand-to metal charge transfer (LMCT) state, which has a short (sub-250 fs) lifetime. From the LMCT state, the complexes decay via internal conversion to lower-lying ligand field (LF) d-d excited states or the vibrationally hot ground electronic state. A minor fraction of the excited complexes relaxes to the LF electronic excited states, which are relatively long-lived with lifetimes >1 ns. Also, in methanol solutions, about 3% of the LMCT-excited copper(II) monochlorocomplexes dissociate forming copper(I) solvatocomplexes and chlorine atoms, which then further react forming long-lived photoproducts. In acetonitrile, about 50% of the LMCT-excited copper(II) monochlorocomplexes dissociate forming radical and ionic products in a ratio of 3:2. Another minor process observed following excitation only in methanol solutions is the re-equilibration between several forms of the copper(II) ground-state complexes present in solutions. This re-equilibration occurs on a time scale from sub-nanoseconds to nanoseconds. PMID- 26901566 TI - Engineering Multi-Walled Carbon Nanotube Therapeutic Bionanofluids to Selectively Target Papillary Thyroid Cancer Cells. AB - BACKGROUND: The incidence of papillary thyroid carcinoma (PTC) has risen steadily over the past few decades as well as the recurrence rates. It has been proposed that targeted ablative physical therapy could be a therapeutic modality in thyroid cancer. Targeted bio-affinity functionalized multi-walled carbon nanotubes (BioNanofluid) act locally, to efficiently convert external light energy to heat thereby specifically killing cancer cells. This may represent a promising new cancer therapeutic modality, advancing beyond conventional laser ablation and other nanoparticle approaches. METHODS: Thyroid Stimulating Hormone Receptor (TSHR) was selected as a target for PTC cells, due to its wide expression. Either TSHR antibodies or Thyrogen or purified TSH (Thyrotropin) were chemically conjugated to our functionalized Bionanofluid. A diode laser system (532 nm) was used to illuminate a PTC cell line for set exposure times. Cell death was assessed using Trypan Blue staining. RESULTS: TSHR-targeted BioNanofluids were capable of selectively ablating BCPAP, a TSHR-positive PTC cell line, while not TSHR-null NSC-34 cells. We determined that a 2:1 BCPAP cell:alpha-TSHR-BioNanofluid conjugate ratio and a 30 second laser exposure killed approximately 60% of the BCPAP cells, while 65% and >70% of cells were ablated using Thyrotropin- and Thyrogen-BioNanofluid conjugates, respectively. Furthermore, minimal non-targeted killing was observed using selective controls. CONCLUSION: A BioNanofluid platform offering a potential therapeutic path for papillary thyroid cancer has been investigated, with our in vitro results suggesting the development of a potent and rapid method of selective cancer cell killing. Therefore, BioNanofluid treatment emphasizes the need for new technology to treat patients with local recurrence and metastatic disease who are currently undergoing either re-operative neck explorations, repeated administration of radioactive iodine and as a last resort external beam radiation or chemotherapy, with fewer side effects and improved quality of life. PMID- 26901569 TI - Species Richness Responses to Structural or Compositional Habitat Diversity between and within Grassland Patches: A Multi-Taxon Approach. AB - Habitat diversity (spatial heterogeneity within and between habitat patches in a landscape, HD) is often invoked as a driver of species diversity at small spatial scales. However, the effect of HD on species richness (SR) of multiple taxa is not well understood. We quantified HD and SR in a wet-dry gradient of open grassland habitats in Hortobagy National Park (E-Hungary) and tested the effect of compositional and structural factors of HD on SR of flowering plants, orthopterans, true bugs, spiders, ground beetles and birds. Our dataset on 434 grassland species (170 plants, 264 animals) showed that the wet-dry gradient (compositional HD at the between-patch scale) was primarily related to SR in orthopterans, ground-dwelling arthropods, and all animals combined. The patchiness, or plant association richness, of the vegetation (compositional HD at the within-patch scale) was related to SR of vegetation-dwelling arthropods, whereas vegetation height (structural HD at the within-patch scale) was related to SR of ground-dwelling arthropods and birds. Patch area was related to SR only in birds, whereas management (grazing, mowing, none) was related to SR of plants and true bugs. All relationships between HD and SR were positive, indicating increasing SR with increasing HD. However, total SR was not related to HD because different taxa showed similar positive responses to different HD variables. Our findings, therefore, show that even though HD positively influences SR in a wide range of grassland taxa, each taxon responds to different compositional or structural measures of HD, resulting in the lack of a consistent relationship between HD and SR when taxon responses are pooled. The idiosyncratic responses shown here exemplify the difficulties in detecting general HD-SR relationships over multiple taxa. Our results also suggest that management and restoration aimed specifically to sustain or increase the diversity of habitats are required to conserve biodiversity in complex landscapes. PMID- 26901570 TI - Imprint Control of BaTiO3 Thin Films via Chemically Induced Surface Polarization Pinning. AB - Surface-adsorbed polar molecules can significantly alter the ferroelectric properties of oxide thin films. Thus, fundamental understanding and controlling the effect of surface adsorbates are crucial for the implementation of ferroelectric thin film devices, such as ferroelectric tunnel junctions. Herein, we report an imprint control of BaTiO3 (BTO) thin films by chemically induced surface polarization pinning in the top few atomic layers of the water-exposed BTO films. Our studies based on synchrotron X-ray scattering and coherent Bragg rod analysis demonstrate that the chemically induced surface polarization is not switchable but reduces the polarization imprint and improves the bistability of ferroelectric phase in BTO tunnel junctions. We conclude that the chemical treatment of ferroelectric thin films with polar molecules may serve as a simple yet powerful strategy to enhance functional properties of ferroelectric tunnel junctions for their practical applications. PMID- 26901572 TI - Safety and efficacy of hematopoietic stem cells mobilization in patients with multiple sclerosis. AB - INTRODUCTION: Multiple sclerosis (MS) is a T-cell-mediated chronic inflammatory disorder of the central nervous system. Several agents have been approved for treatment of MS, however their efficacy is limited and short term. Autologous hematopoietic stem cell (HSC) transplantation may remain an encouraging option for some MS patients who failed prior conventional treatment. OBJECTIVE: To assess the safety and effectiveness of HSCs mobilization in patients with MS. MATERIAL AND METHODS: Thirty-nine patients (20 females, 19 males) with relapsing remitting MS at median age of 40 years (range 25-63) were included in this study. As a stem cell mobilization they received either granulocyte colony-stimulating factor (G-CSF) alone (10 MUg/kg s.c. daily; n = 1) or cyclophosphamide (CY; 2.0 g/m2 i.v. on days 1-2) followed by G-CSF (n = 38). RESULTS: The median number of mobilized HSCs per kilogram was 6.32 * 106 (range 2.64-26.3 * 106). One apheresis was sufficient for collection of HSCs in 30 out of 39 MS patients (77%). Two aphereses were required for seven patients, three for one patient, and four for one patient (17, 3, and 3%, respectively). Side effects of HSCs mobilization have been reported for eight patients (30%) and they were as follows: Staphylococcus epidermidis bacteremia (n = 1), fever of unknown origin (n = 3), diarrhea (n = 3), and headache (n = 1). CONCLUSIONS: Mobilization using CY and/or G-CSF resulted in effective mobilization in all MS patients. This procedure was found to be safe. No fatal outcome has been reported. PMID- 26901571 TI - Abstract Conceptual Feature Ratings Predict Gaze Within Written Word Arrays: Evidence From a Visual Wor(l)d Paradigm. AB - The Abstract Conceptual Feature (ACF) framework predicts that word meaning is represented within a high-dimensional semantic space bounded by weighted contributions of perceptual, affective, and encyclopedic information. The ACF, like latent semantic analysis, is amenable to distance metrics between any two words. We applied predictions of the ACF framework to abstract words using eyetracking via an adaptation of the classical "visual word paradigm" (VWP). Healthy adults (n = 20) selected the lexical item most related to a probe word in a 4-item written word array comprising the target and three distractors. The relation between the probe and each of the four words was determined using the semantic distance metrics derived from ACF ratings. Eye movement data indicated that the word that was most semantically related to the probe received more and longer fixations relative to distractors. Importantly, in sets where participants did not provide an overt behavioral response, the fixation rates were nonetheless significantly higher for targets than distractors, closely resembling trials where an expected response was given. Furthermore, ACF ratings which are based on individual words predicted eye fixation metrics of probe-target similarity at least as well as latent semantic analysis ratings which are based on word co occurrence. The results provide further validation of Euclidean distance metrics derived from ACF ratings as a measure of one facet of the semantic relatedness of abstract words and suggest that they represent a reasonable approximation of the organization of abstract conceptual space. The data are also compatible with the broad notion that multiple sources of information (not restricted to sensorimotor and emotion information) shape the organization of abstract concepts. While the adapted "VWP" is potentially a more metacognitive task than the classical visual world paradigm, we argue that it offers potential utility for studying abstract word comprehension. PMID- 26901573 TI - Changes in structural and metabolic muscle characteristics following exercise based interventions in patients with COPD: a systematic review. AB - Patients with COPD suffer from lower-limb muscle dysfunction characterized by lower muscle oxidative capacity and muscle mass. Exercise-based training is expected to attenuate lower-limb intramuscular characteristics, but a detailed systematic approach to review the available evidence has not been performed yet. PUBMED and PEDro databases were searched. Twenty-five studies that implemented an exercise-based training program (aerobic and/or resistance training, high intensity interval training, electrical or magnetic stimulation) and reported muscle biopsy data of patients with COPD were critically appraised. The coverage of results includes changes in muscle structure, muscle protein turnover regulation, mitochondrial enzyme activity, oxidative and nitrosative stress, and inflammation after exercise-based training interventions. Study design and training modalities varied among studies, which partly explains the observed heterogeneous response in muscle characteristics. Gaps in the current knowledge are identified and recommendations for future research are made to enhance our knowledge on exercise training effects in patients with COPD. PMID- 26901574 TI - Rapid improvements in pain and quality of life are sustained after surgery for spinal metastases in a large prospective cohort. AB - Introduction Metastatic spinal cancer is a common condition that may lead to spinal instability, pain and paralysis. In the 1980s, surgery was discouraged because results showed worse neurological outcomes and pain compared with radiotherapy alone. However, with the advent of modern imaging and spinal stabilisation techniques, the role of surgery has regained centre stage, though few studies have assessed quality of life and functional outcomes after surgery. Objective We investigated whether surgery provides sustained improvement in quality of life and pain relief for patients with symptomatic spinal metastases by analysing the largest reported surgical series of patients with epidural spinal metastases. Methods A prospective cohort study of 922 consecutive patients with spinal metastases who underwent surgery, from the Global Spine Tumour Study Group database. Pre- and post-operative EQ-5D quality of life, visual analogue pain score, Karnofsky physical functioning score, complication rates and survival were recorded. Results Quality of life (EQ-5D), VAS pain score and Karnofsky physical functioning score improved rapidly after surgery and these improvements were sustained in those patients who survived up to 2 years after surgery. In specialised spine centres, the technical intra-operative complication rate of surgery was low, however almost a quarter of patients experienced post-operative systemic adverse events. Conclusion Surgical treatment for spinal metastases produces rapid pain relief, maintains ambulation and improves good quality of life. However, as a group, patients with cancer are vulnerable to post-operative systemic complications, hence the importance of appropriate patient selection. PMID- 26901575 TI - Nonlinear Mechanics of Athermal Branched Biopolymer Networks. AB - Naturally occurring biopolymers such as collagen and actin form branched fibrous networks. The average connectivity in branched networks is generally below the isostatic threshold at which central force interactions marginally stabilize the network. In the submarginal regime, for connectivity below this threshold, such networks are unstable toward small deformations unless stabilized by additional interactions such as bending. Here we perform a numerical study on the elastic behavior of such networks. We show that the nonlinear mechanics of branched networks is qualitatively similar to that of filamentous networks with freely hinged cross-links. In agreement with a recent theoretical study,1 we find that branched networks also exhibit nonlinear mechanics consistent with athermal critical phenomena controlled by strain. We obtain the critical exponents capturing the nonlinear elastic behavior near the critical point by performing scaling analysis of the stiffening curves. We find that the exponents evolve with the connectivity in the network. We show that the nonlinear mechanics of disordered networks, independent of the detailed microstructure, can be characterized by a strain-driven second-order phase transition, and that the primary quantitative differences among different architectures are in the critical exponents describing the transition. PMID- 26901576 TI - Efficacy and safety of vi-tetanus toxoid conjugated typhoid vaccine (PedaTyphTM) in Indian children: School based cluster randomized study. AB - Vi polysaccharide typhoid vaccines cannot be used in children <2 years owing to poor immunogenic and T cell independent properties. Conjugate vaccine prepared by binding Vi to tetanus toxoids (Vi-TT) induces protective levels even in children <2 years. We evaluated efficacy and safety following vaccination with a Vi-TT vaccine in children 6 months to 12 years of age. Overall, 1765 subjects were recruited from two registered municipal urban slums of southern Kolkata. Most of the children of the slum dwellers attended the schools in the locality which was selected with permission from the school authority. Schools were randomly divided into vaccinated (Test group) and unvaccinated group (Control group). Children and their siblings of test group received 2-doses of PedaTyphTM vaccine at 6 weeks interval. Control group received vaccines as per national guidelines. Adverse events (AEs) were examined after 30 minutes, 1 month and clinical events were observed till 12 months post-vaccination. Incidence of culture positive typhoid fever in the control group was 1.27% vis-a-vis none in vaccine group during 12 months. In subgroup evaluated for immunogenicity, an antibody titer value of 1.8 EU/ml (95% CI: 1.5 EU/ml, 2.2 EU/ml), 32 EU/ml (95% CI: 27.0 EU/ml, 39.0 EU/ml) and 14 EU/ml (95% CI: 12.0 EU/ml, 17.0 EU/ml) at baseline, 6 weeks and 12 months, respectively was observed. Sero-conversion among the sub-group was 100% after 6 weeks of post-vaccination and 83% after 12 months considering 4-fold rise from baseline. The efficacy of vaccine was 100 % (95% CI: 97.6%, 100%) in the first year of follow-up with minimal AEs post vaccination. Vi conjugate typhoid vaccine conferred 100% protection against typhoid fever in 1765 children 6 months to 12 years of age with high immunogenicity in a subgroup from the vaccine arm. PMID- 26901577 TI - Epigenetic regulation in dental pulp inflammation. AB - Dental caries, trauma, and other possible factors could lead to injury of the dental pulp. Dental infection could result in immune and inflammatory responses mediated by molecular and cellular events and tissue breakdown. The inflammatory response of dental pulp could be regulated by genetic and epigenetic events. Epigenetic modifications play a fundamental role in gene expression. The epigenetic events might play critical roles in the inflammatory process of dental pulp injury. Major epigenetic events include methylation and acetylation of histones and regulatory factors, DNA methylation, and small non-coding RNAs. Infections and other environmental factors have profound effects on epigenetic modifications and trigger diseases. Despite growing evidences of literatures addressing the role of epigenetics in the field of medicine and biology, very little is known about the epigenetic pathways involved in dental pulp inflammation. This review summarized the current knowledge about epigenetic mechanisms during dental pulp inflammation. Progress in studies of epigenetic alterations during inflammatory response would provide opportunities for the development of efficient medications of epigenetic therapy for pulpitis. PMID- 26901578 TI - Women and functional dyspepsia. AB - Functional dyspepsia is relatively common yet poorly understood. The best accepted diagnostic criteria are the Rome III criteria. The epidemiology, healthcare seeking rates, impact and pathophysiology are reviewed with a focus on women. Treatment is limited with no clearly established regimen currently recommended. Duodenal eosinophilia may be found in a subset. Proton pump inhibitors and prokinetic agents represent the standard therapeutic regimen after Helicobacter pylori infection has been eliminated. Some novel agents such as the prokinetic acotiamide appear promising; however, the need for a safe and efficacious treatment remains largely unmet. This review also describes the currently available management options for functional dyspepsia. PMID- 26901581 TI - [Uses of scientific information and conflicts of interest]. AB - Conflicts of interest are defined as a situation in which a primary goal (such as individual or collective health, or access to information) conflicts with a secondary goal. Conflicts of interest arise for several reasons and under different circumstances: not only in relation to private profits, but also for reasons related to career or social roles. Conflicts of interest are very common and require increasing awareness in democratic societies that pursue primary goals such as health and independent information. The increasing role of profit oriented private industry and interactions between private enterprises and public research institutions (for example in research on drugs or alternative sources of energy) require that the safeguard role of the State be strengthened. Also State institutions, however, may be affected by conflicts of interest. Simple disclosure of conflicts is necessary but not sufficient to tackle them. These themes are discussed in the paper referring to two recent examples: an alleged access of total mortality in Italy in 2015, and the carcinogenicity of red meat. PMID- 26901579 TI - Rhizosecretion improves the production of Cyanovirin-N in Nicotiana tabacum through simplified downstream processing. AB - Rhizosecretion has many advantages for the production of recombinant pharmaceuticals, notably facile downstream processing from hydroponic medium. The aim of this study was to increase yields of the HIV microbicide candidate, Cyanovirin-N (CV-N), obtained using this production platform and to develop a simplified methodology for its downstream processing from hydroponic medium. Placing hydroponic cultures on an orbital shaker more than doubled the concentration of CV-N in the hydroponic medium compared to plants which remained stationary, reaching a maximum of approximately 20MUg/ml in one week, which is more than 3 times higher than previously reported yields. The protein composition of the hydroponic medium, the rhizosecretome, was characterised in plants cultured with or without the plant growth regulator alpha-napthaleneacetic acid by LC-ESI-MS/MS, and CV-N was the most abundant protein. The issue of large volumes in the rhizosecretion system was addressed by using ion exchange chromatography to concentrate CV-N and partially remove impurities. The semi purified CV-N was demonstrated to bind to HIV gp120 in an ELISA and to neutralise HIVBa-L with an IC50 of 6nM in a cell-based assay. Rhizosecretion is therefore a practicable and inexpensive method for the production of functional CV-N. PMID- 26901582 TI - [Ethical use of antibiotics in the era of multiresistance: a common good for the individual or the society?]. AB - Common goods refer to goods that may be used by anyone belonging to the community that has use rights over a commons and are fundamental to people's lives. Appropriate measures for safeguarding common goods should be undertaken, also for the benefit of future generations. Drugs in general, and antibiotics in particular, should be considered a common good as well. However, antibiotic use confined to the individual health benefit not only leads to less favorable outcomes for the society but also results in the development of antimicrobial resistance in the individual patient. This phenomenon is termed "tragedy of the commons" and identifies the impossibility of achieving over time the optimal treatment for each individual subject/patient. As a consequence, pursuing individual interests may lead to societal detriment. Conversely, restricting antibiotic prescriptions (e.g., avoiding overuse or misuse of last-generation antibiotics for the treatment of an infection) is not harmful for the individual, would benefit society with increased efficacy, and does not favor the emergence of antibiotic resistance. In this editorial, several suggestions as to how antibiotics should be appropriately used are provided in accordance with distributive justice principles, where individual and social interests meet. PMID- 26901583 TI - [Relationship between 25-hydroxy vitamin D and cognitive status in older adults: the COGNIDAGE study]. AB - AIM: The aim of the COGNIDAGE study was to examine the association between 25(OH)D and cognitive status in a group of elderly patients with vitamin D deficiency and high burden of comorbidities attending Geriatric Outpatient Clinics. MATERIALS AND METHODS: We studied the relationship between 25(OH)D and cognitive functions taking into account comorbidities and cognitive functions assessed by MMSE (Mini Mental State Examination), CDT (Clock Drawing Test) and CIRS (Cumulative Illness Rating Scale), in 132 consecutive elderly patients with low levels of 25(OH)D (<10 ng/ml) compatible with the condition of vitamin deficiency. The association among 25(OH)D levels, MMSE score, CDT score and CIRS scores were analyzed using Pearson correlation. All the elderly patients received an adequate vitamin D supplementation and were reassessed after 6 months. RESULTS: At baseline, mean MMSE and CIRS scores were: 21.8+5.56 and 2.96 +1.63 respectively. Mean CDT score was 3,66+-2.05. No associations were found between 25(OH)D levels and global cognitive function. A significant relationship was observed between the total CIRS score and 25(OH)D levels (r=0.305; p=0.000) as well as between total CIRS score and MMSE (r=-0.375; p=0.000). After 6 months, 83.9 % had 25(OH)D levels >20 ng/ml. Mean MMSE and CDT scores were 22.20+-5.76 and 3.90+-2.06 respectively. There was no significant correlation among 25(OH)D, MMSE and CDT scores while a significant correlation was found between 25(OH)D and CIRS- severity score (r=0.275; p=0.001) and between MMSE and total CIRS scores (r=-0.247; p=0.005 for CIRS-comorbidities; r=-0.184; p=0.04 for CIRS-severity). A post hoc evaluation on two subgroups of elderly patients (the first with vitamin D deficiency without cognitive impairment, the second with vitamin D deficiency and dementia) showed a statistically significant difference (p=0.00001) regarding the CIRS-comorbidities scores. CONCLUSIONS: In our cohort of elderly patients with a high burden of comorbidities, 25(OH)D low levels (<10 ng/ml) are not associated with MMSE and CDT scores. There is no statistically difference among the levels of 25(OH)D and MMSE and CDT scores after 6 months. The strong correlation we found regarding CIRS-comorbidities in the two sub-groups suggests that vitamin D deficiency may play a role in promoting cognitive impairment only with comorbidities. PMID- 26901584 TI - [Decisional framework for varicella vaccine: challenges in the face of opportunity]. AB - INTRODUCTION: Decision makers adopt interventions, including vaccines, which are most beneficial to populations. A transparent, unbiased, and comprehensive framework based on evidence-based criteria is a promising tool to guide decision making on vaccine adoption: we developed a multi-dimensional framework conceived from the DECIDE - Evidence to decision Framework (EtD framework). We validated the framework by conducting a real data and evidence set collection on varicella vaccination and tested it with a multidisciplinary group. METHODS: The EtD framework presented evidence concerning the varicella vaccination organized in six dimensions: Burden of disease, Vaccine characteristics and impact of immunization program, Values and preferences, Resource use, Equity and Feasibility. Two reviewers completed each dimension with information about varicella vaccine. A multidisciplinary group of 42 participants were asked to evaluate the information in the framework, decide whether to introduce varicella vaccine in the national immunization program, assess the usefulness, and propose some impovements of the decision-making tool. RESULTS: From 33 responders (79%) out of 42, 61% supported the adoption of the varicella vaccine as part of the national immunization program. A half (50%) favored the monovalent vaccine while the other half chose the tetravalent vaccine. About 90% of responders found information in the EtD framework comprehensive, easy to understand, and presented in a way that helped make decisions. CONCLUSIONS: Complete and transparent information are welcome. The EtD identified a situation of important divergences between policy makers regarding the introduction and the choice of vaccine. In our case study, for example, a third of the multidisciplinary group did not recommend the adoption of varicella vaccine. PMID- 26901586 TI - Study of the major essential oil compounds of Coriandrum sativum against Acinetobacter baumannii and the effect of linalool on adhesion, biofilms and quorum sensing. AB - Acinetobacter baumannii is a pathogen that has the ability to adhere to surfaces in the hospital environment and to form biofilms which are increasingly resistant to antimicrobial agents. The aim of this work was to study the antimicrobial activity of the major oil compounds of Coriandrum sativum against A. baumannii. The effect of linalool on planktonic cells and biofilms of A. baumannii on different surfaces, as well as its effect on adhesion and quorum sensing was evaluated. From all the compounds evaluated, linalool was the compound with the best antibacterial activity, with minimum inhibitory concentration values between 2 and 8 MUl ml(-1). Linalool also inhibited biofilm formation and dispersed established biofilms of A. baumannii, changed the adhesion of A. baumannii to surfaces and interfered with the quorum- sensing system. Thus, linalool could be a promising antimicrobial agent for controlling planktonic cells and biofilms of A. baumannii. PMID- 26901587 TI - Mini-review: Biofilm responses to oxidative stress. AB - Biofilms constitute the predominant microbial style of life in natural and engineered ecosystems. Facing harsh environmental conditions, microorganisms accumulate reactive oxygen species (ROS), potentially encountering a dangerous condition called oxidative stress. While high levels of oxidative stress are toxic, low levels act as a cue, triggering bacteria to activate effective scavenging mechanisms or to shift metabolic pathways. Although a complex and fragmentary picture results from current knowledge of the pathways activated in response to oxidative stress, three main responses are shown to be central: the existence of common regulators, the production of extracellular polymeric substances, and biofilm heterogeneity. An investigation into the mechanisms activated by biofilms in response to different oxidative stress levels could have important consequences from ecological and economic points of view, and could be exploited to propose alternative strategies to control microbial virulence and deterioration. PMID- 26901588 TI - Addendum. PMID- 26901589 TI - Corrigendum. PMID- 26901590 TI - Stress-related increases in risk taking and attentional failures predict earlier relapse to smoking in young adults: A pilot investigation. AB - Substantial evidence links greater impulsivity and stress exposure to poorer smoking cessation outcomes. Results from adolescents also indicate that stress related change in risk taking can impede cessation attempts. We investigated the effects of stress-related change in impulsivity, risk taking, attention and nicotine withdrawal, and craving in young adult smokers on time to smoking relapse in a relapse analogue paradigm. Twenty-six young adult smokers (50% women; mean age: 20.9 +/- 1.8) were exposed to a stress imagery session followed by a contingency management-based relapse analogue paradigm. Participants smoked at least 5 cigarettes daily, with a mean baseline carbon monoxide (CO) level of 13.7 (+/- 5.1) ppm. Repeated measures analysis of variance (ANOVA) and paired t tests examined stress induction validity and Cox regressions of proportional hazards examined the effects of stress-related changes in nicotine withdrawal, nicotine craving, attention, impulsivity, and risk taking on time to relapse. While stress-related change in impulsivity, nicotine craving and withdrawal did not predict time to relapse (all ps > .10), greater stress-related increases in reaction time (RT) variability (p = .02) were predictive of shorter time to relapse, with trend-level findings for inattention and risk taking. Furthermore, changes in stress-related risk taking affected outcome in women more than in men, with a significant relationship between stress-related change in risk taking only in women (p = .026). Smoking cessation attempts in young adults may be adversely impacted by stress-related increases in risk taking and attentional disruption. Clinicians working with young adults attempting cessation may need to target these stress-related impairments by fostering more adaptive coping and resilience. PMID- 26901591 TI - Effects of gaboxadol on the expression of cocaine sensitization in rats. AB - Behavioral sensitization to psychostimulants is associated with changes in dopamine (DA), glutamate, and GABA within the mesocorticolimbic and nigrostriatal DA systems. Because GABAA receptors are highly expressed within these systems, we examined the role of these receptors containing a delta subunit in cocaine behavioral sensitization. Experiment 1 examined the effects of Gaboxadol (GBX, also known as THIP [4,5,6,7-tetrahydro-isoxazolo[5,4-c]pyridin-3-ol]), a selective delta-GABAA receptor agonist, on the locomotor responses to acute cocaine. GBX at 1.25 mg/kg produced locomotor depression in female rats alone. We then examined the effects of GBX on the expression of cocaine-induced locomotion and stereotypy in female and male rats treated with 5 days of cocaine (15 mg/kg) followed by cocaine challenge 7 days later. We administered systemic (Experiment 2) or intranucleus accumbens (intra-NAC; Experiment 3) injections of GBX (0, 1.25, 2.5, 5, or 10 mg/kg subcutaneously, or 1 MUmol/L or 1 mM intra-NAC, respectively) prior to cocaine challenge (10 mg/kg). In our experiments females were robustly sensitized to cocaine at low dose whereas males did not show such sensitization-limiting comparisons between the 2 sexes. Sensitized females showed a biphasic response to low (1.25 mg/kg and 1 MUmol/L) and high (10 mg/kg and 1 mM) dose GBX whereas nonsensitized males showed this pattern only following intra NAC injection. Immunohistochemical analysis of the NAC revealed that females have more delta-containing GABAA receptors than do males and that following chronic cocaine injections this difference persisted (Experiment 4). Together, our results support the notion of the key role of extrasynaptic GABAA delta-subunit containing receptors in cocaine sensitization. PMID- 26901592 TI - Differences in weekday versus weekend drinking among nonstudent emerging adults. AB - In the current investigation, we sought to examine "day-of-the-week" drinking of an at-risk sample of nonstudent emerging adults and whether specific factors are associated with differential drinking patterns. Our study aims were to (a) identify differences in weekday versus weekend drinking, and (b) examine specific expectancies (i.e., sociability, tension reduction) and demographic factors (e.g., age, sex) relating to weekend versus weekday drinking after controlling for harmful drinking and holiday drinking. Participants were heavy-drinking noncollege attenders recruited from the community (N = 238; 63.4% men, 35.7% women; M age = 21.92 years). They reported daily drinking for the previous 30 days and completed measures of harmful drinking, alcohol expectancies, and demographic information. Results showed that more drinks were consumed on the weekends (i.e., Thursday to Saturday) than weekdays, with 63% of drinks consumed on weekends. Multilevel modeling analyses indicated that weekday drinking was associated with tension-reduction expectancies, social expectancies, sex, and age. Weekend-drinking increases were related to social expectancies, but not tension-reduction expectancies. Our final model indicated that, after controlling for the effect of holiday drinking, the within-person weekday-weekend distinction explained 18% of the total variance. In general, our findings highlight the importance of alcohol expectancies and drinking contexts in understanding the drinking behaviors of nonstudents. The differential role of tension-reduction and social-facilitation expectancies on drinking throughout the week imply that different cognitive pathways are involved in weekday versus weekend drinking, and both types of expected alcohol effects should be targets of risk-reduction efforts with nonstudent drinkers. PMID- 26901593 TI - Lectin-like oxidized low density lipoprotein receptor 1-deficient mice show resistance to instability-induced osteoarthritis. AB - OBJECTIVES: The lectin-like oxidized low density lipoprotein (ox-LDL) receptor 1 (LOX-1)/ox-LDL system, which contributes to the pathogenesis of atherosclerosis, may be involved in the development of osteoarthritis (OA). However, the mechanisms by which the LOX-1/ox-LDL system contributes to OA development in vivo are unclear. In this study, we investigated the direct involvement of LOX-1/ox LDL in OA development by using LOX-1-knockout (LOX-1(-)/(-)) mice in a joint instability-induced model of OA. METHOD: OA development was evaluated with histological scoring at 4 and 8 weeks after surgery to induce knee destabilization in LOX-1(+)/(+) and LOX-1(-)/(-) mice. Immunohistological analysis was used to evaluate the expression of LOX-1, ox-LDL, Runt-related transcription factor 2 (Runx2), and type X collagen (COL X) in articular chondrocytes and osteophyte-forming cells. In addition, double immunofluorescence staining was performed to determine the relationships between LOX-1 and Runx2 or COL X expression. RESULTS: In the model of knee destabilization, symptoms were significantly suppressed in LOX-1(-)/(-) mice. LOX-1, ox-LDL, Runx2, and COL X were overexpressed in articular chondrocytes and osteophyte-forming cells in LOX 1(+)/(+) mice and were significantly downregulated in articular chondrocytes and osteophyte-forming cells in LOX-1(-)/(-) mice compared with those in LOX-1(+)/(+) mice. Double immunostaining indicated that LOX-1 localization coincided with Runx2 and COL X expression. CONCLUSIONS: These data indicate that the LOX-1/ox LDL system plays a pivotal role in the pathogenesis of instability-induced OA through endochondral ossification. LOX-1-positive chondrocytes and osteophyte forming cells may be possible targets to prevent disease progression in OA. PMID- 26901594 TI - Hospitalization after Cataract Surgery in a Nationwide Managed-Care Population. AB - PURPOSE: Little is known regarding the extent by which patients undergoing outpatient cataract surgery are at risk for postoperative hospitalization. We sought to determine the percentage of patients undergoing cataract surgery who were subsequently hospitalized, the patient characteristics associated with postoperative hospitalization, and the reasons for hospitalization. METHODS: We identified all beneficiaries of a large U.S. managed care network age >=40 years old who underwent >=1 cataract surgery from 2001-2011. All enrollees who required inpatient hospitalization within 7, 14, 30, and 90 days following initial cataract surgery and the reasons for hospitalization were determined. Logistic regression was performed to assess factors that significantly impacted the odds of requiring postoperative hospitalization. RESULTS: Among the 64,981 patients who underwent cataract surgery, rates of hospitalization within 7, 14, 30, and 90 days were 0.3%, 0.5%, 1.3% and 4.2%, respectively. Among the 10,674 patients who had no major preexisting medical comorbidities, 0.1% were hospitalized within 7 days. The odds of hospitalization increased by 35% (OR = 1.35 [CI, 1.23-1.48]) with the presence of each additional comorbidity and by 14% with each additional hospitalization in the 3 years prior to cataract surgery (OR = 1.14 [CI, 1.10 1,18]). Those who were hospitalized in the 30 days prior to cataract surgery had 524% increased odds of being hospitalized within 7 days after cataract surgery (OR = 6.24, [CI, 3.37-11.57]) compared to those with no record of preoperative hospitalization. Postoperative hospitalizations were most commonly due to cardiovascular conditions, comprising over 25% of primary diagnoses associated with hospitalization. CONCLUSIONS: The risk of hospitalization after cataract surgery is low, and is very low among those with no major preexisting medical comorbidities. Opportunities may exist to limit comprehensive preoperative evaluation and testing to those who have serious pre-existing medical comorbidities. PMID- 26901595 TI - Organ-on-a-Chip Systems: Microengineering to Biomimic Living Systems. AB - "Organ-on-a-chip" systems integrate microengineering, microfluidic technologies, and biomimetic principles to create key aspects of living organs faithfully, including critical microarchitecture, spatiotemporal cell-cell interactions, and extracellular microenvironments. This creative platform and its multiorgan integration recapitulating organ-level structures and functions can bring unprecedented benefits to a diversity of applications, such as developing human in vitro models for healthy or diseased organs, enabling the investigation of fundamental mechanisms in disease etiology and organogenesis, benefiting drug development in toxicity screening and target discovery, and potentially serving as replacements for animal testing. Recent advances in novel designs and examples for developing organ-on-a-chip platforms are reviewed. The potential for using this emerging technology in understanding human physiology including mechanical, chemical, and electrical signals with precise spatiotemporal controls are discussed. The current challenges and future directions that need to be pursued for these proof-of-concept studies are also be highlighted. PMID- 26901596 TI - Pharmaco-EEG Studies in Animals: An Overview of Contemporary Translational Applications. AB - The contemporary value of animal pharmaco-electroencephalography (p-EEG)-based applications are strongly interlinked with progress in recording and neuroscience analysis methodology. While p-EEG in humans and animals has been shown to be closely related in terms of underlying neuronal substrates, both translational and back-translational approaches are being used to address extrapolation issues and optimize the translational validity of preclinical animal p-EEG paradigms and data. Present applications build further on animal p-EEG and pharmaco-sleep EEG findings, but also on stimulation protocols, more specifically pharmaco-event related potentials. Pharmaceutical research into novel treatments for neurological and psychiatric diseases has employed an increasing number of pharmacological as well as transgenic models to assess the potential therapeutic involvement of different neurochemical systems and novel drug targets as well as underlying neuronal connectivity and synaptic function. Consequently, p-EEG studies, now also readily applied in modeled animals, continue to have an important role in drug discovery and development, with progressively more emphasis on its potential as a central readout for target engagement and as a (translational) functional marker of neuronal circuit processes underlying normal and pathological brain functioning. In a similar vein as was done for human p-EEG studies, the contribution of animal p-EEG studies can further benefit by adherence to guidelines for methodological standardization, which are presently under construction by the International Pharmaco-EEG Society (IPEG). PMID- 26901597 TI - Newborn Screening for Sickle Cell Disease: Jamaican Experience. AB - Objectives: To review the history of newborn screening for sickle cell disease with especial reference to Jamaica. Methods: A summary was done of the history, the development of associated laboratory technology and the implementation of newborn screening for sickle cell disease in Jamaica. Results: Screening was initiated at Victoria Jubilee Hospital, Kingston from 1973-1981, reactivated in 1995 and extended to the University Hospital of the West Indies in 1997 and to Spanish Town Hospital in 1998. From August 2008, there was a progressive recruitment of 12 hospitals in the south and west of Jamaica which has raised the frequency of islandwide newborn coverage from 25% in 1973 to 81%. The results of this extended programme in southwest Jamaica are presented. Dried blood spots collected from the umbilical cord proved stable, cheap and efficient; mean sample collection rates were 98%, maternal contamination occurred in < 1% and caused diagnostic confusion in < 0.1%. By March 31, 2015, a total of 54 566 births have been screened, detecting 161 with homozygous sickle cell (SS) disease, 125 with sickle cell-haemoglobin C (SC) disease and 36 with sickle cell-beta thalassaemia. Of the 327 babies with clinically significant sickle cell syndromes, all except five who died within seven days of birth were confirmed by four to six weeks and recruited to local sickle cell clinics. Conclusion: Early detection of sickle cell disease and recruitment to clinics is known to reduce its morbidity and mortality. The methods currently detailed provide an effective and economic model of newborn screening which may be of value elsewhere. PMID- 26901599 TI - Trona Causes Fetal Loss in Pregnant Rat via an Oestrogen-dependent Mechanism. AB - Background: There is a claim in folklore medicine in Nigeria that trona (a sesquicarbonate or hydrated carbonate of sodium) causes fetal loss. However, this has not been substantiated or refuted by any scientific evidence. Aim: This study evaluates whether or not trona causes fetal loss in pregnant female Wistar rats. Methods: Pregnant Wistar rats of comparable weights were randomized into three groups. Group A (control) was given a single dose of 1.25 mL/kg body weight of lime while groups B and C were given 250 mg/kg and 500 mg/kg body weight of trona, respectively. Results: There was no significant difference in the body weight gained across all the groups. The dose of 250 mg/kg body weight of trona decreased the number of live fetus, while 500 mg/kg body weight produced no live fetus; 250 mg/kg and 500 mg/kg body weight of trona led to fetal loss rate of 83.33% and 100%, respectively. Trona also reduced the concentrations of serum progesterone and cholesterol, and increased serum oestradiol. Conclusion: This study revealed that trona causes fetal loss. This is possibly via an oestrogen dependent mechanism, and attributed to the chemical constituents of trona. PMID- 26901598 TI - Beta-lactamase Enzymes of Clinical Pseudomonas aeruginosa Strains. AB - Objectives: In this study, the production of extended spectrum beta-lactamase (ESBL), metallo-betalacatamase (MBL) and AmpC beta-lactamase enzymes of Pseudomonas aeruginosa (P aeruginosa) strains which were isolated from clinical samples were investigated. AmpC gene was also detected by the polymerase chain reaction (PCR) analysis. Methods: A hundred strains of P aeruginosa were included in the study. The presence of ESBL was investigated with combined disk confirmation test, MBL was investigated with E-test method and AmpC beta lactamase was investigated with disk induction test. In order to detect the production of AmpC betalactamase genotypically, the PCR method was used. Results: Only one strain was found to be MBL positive. Four per cent of strains were found to be ESBL positive. AmpC beta-lactamase production was positive in 73% of the strains with disk induction test. AmpC gene was detected in 96% of the studied strains with the PCR method. Conclusion: While ESBL and MBL rates in this study were significantly lower than those found in other studies, the rate of AmpC beta lactamase was higher. Although AmpC gene was detected in some strains (23%), they were not found to produce AmpC beta-lactamase with disk induction test. PMID- 26901600 TI - Alterations in Gold Nanoparticle Levels Are Size Dependent, with the Smaller Ones Inducing the Most Toxic Effects and Related to the Time of Exposure of the Gold Nanoparticles. AB - Background: Gold nanoparticle (GNP) levels in the blood of rats in vivo have not been previously documented. This study aimed to evaluate the influence of size and exposure duration of GNPs on the gold levels in the blood of rats in vivo. Methods: Thirty rats were divided into five groups, NG = control group, G1A: infusion of 10 nm GNPs for three days, G1B: 10 nm GNPs for seven days, G2A: 50 nm GNPs for three days and G2B: 50 nm GNPs for seven days. Fifty microlitres of GNPs dissolved in aqueous solution were administered intraperitoneally every day for three and seven days. Gold concentrations in different samples were measured using inductively coupled plasma-optical emission spectrometer (ICP-OES). Results: The percentage normalized value of 50nm GNPs increased in the blood of rats in both three and seven days when compared with 10 nm GNPs. Conclusions: It became evident from the results of this study that the alterations in GNP levels were size dependent, with the smaller ones inducing the most toxic effects and related to the time of exposure of GNPs. The results might indicate that the smaller GNPs are mostly taken up and accumulate in the different rat organs, suggesting their toxic effects, while the 50 nm GNPs are retained in the blood of rats for a long time. These conclusions are further supported by the histological investigation. PMID- 26901601 TI - Different Doses and Routes of Administration of Methimazole Affect Thyroid Status in Methimazole-induced Hypothyroidism in Rats. AB - Objective: It is agreed that methimazole (MMI) can be administered to induce hypothyroidism. However, there are conflicting data about its effect on thyroid function and development in rats through different administrations. In the present study, we established and compared differences of the rat hypothyroid model induced by MMI added to drinking water or given through an intragastric tube. Methods: Sixty-four male Wistar rats were randomly divided into seven groups. Methimazole was added to the drinking water (0.025%, 0.04% or 0.1% wt/vol), or through intragastric gavage (5 mg/100 g body weight (bw) or 8 mg/100 g bw) one time each day for 21 days. The rats were weighed every seven days. Blood samples were taken in order to detect the concentrations of serum triiodothyronine (T3), thyroxine (T4) and thyrotropin (TSH) at the end of the experiments. Results: Our results indicate that the effect of methimazole on a rat's thyroid function and body weight is similar in both the group given 0.1% concentration in drinking water and the group which received 8 mg/100 g bw once daily through the intragastric tube. Also, a similar effect was observed in the 0.025%, 0.04% and 5 mg/100 g bw groups. Conclusion: These findings suggest that a relationship between the concentration of MMI by oral administration and the dose of it through intragastric administration could exist, and may contribute to inducing hypothyroidism in rats. PMID- 26901602 TI - Investigation by the Method of INNO-LiPA of Primary Resistance to Lamivudine in Patients with Chronic Hepatitis B Who Have Not Used Antiviral Therapy. AB - Aim: Two billion people around the world are exposed to the hepatitis B virus (HBV) and about 350 million are infected with chronic HBV. The infection can be acquired early (neonatal) and becomes chronic in 90%; this rate reduces to 30% between ages one and five years. There is a 25% risk of chronicity in adults. Nowadays, immunomodulatory and antiviral pegylated-interferons or oral antiviral agents are used in the treatment of chronic hepatitis B. Lamivudine is an effective oral antiviral agent which inhibits the replication of HVB by blocking reverse transcriptase enzyme. The study aims to detect the resistance of HBV to lamivudine in the community and evaluate the effectiveness and suitability of early treatment with lamivudine. Subjects and Methods: One hundred patients who presented to our Faculty of Medicine Hospital Infectious Diseases and Clinical Microbiology Department and had not received any antiviral treatment were recruited. The INNO-LiPA method was applied to investigate primary lamivudine resistance in patients. Results: Seventy-eight patients were HBeAg-negative and 22 patients were HBeAg-positive. A statistically significant correlation was found between HBeAg positivity, alanine aminotransferase (ALT) elevation and HBV DNA (p < 0.05). The rtM204V and L180M mutation motif was found in one patient with HBeAg positivity. Conclusions: Hepatitis B virus in our region is not a lamivudine-resistant strain and early treatment with lamivudine is an effective and convenient method. PMID- 26901603 TI - The Investigation of Plasma Glucagon-like Peptide-1 Levels in Newly Diagnosed Type 1 Diabetic Children. AB - Objective: To reveal the possible role of glucagon-like peptide-1 (GLP-1) in newly diagnosed Type 1 diabetic children. Methods: Twenty-five newly diagnosed children and 22 healthy children were included in the study. Results: In oral glucose tolerance tests, no correlation was observed between C-peptide and GLP-1 levels at 0 and 30 minutes, and plasma GLP-1 levels in both groups at 0 and 30 minutes were not statistically different. Conclusion: Consequently, fasting and postprandial GLP-1 levels in newly diagnosed Type 1 diabetic children are not different from healthy children. Glucagon-like peptide-1 levels in newly diagnosed Type 1 diabetic children suggest that plasma GLP-1 levels do not have any role in the pathogenesis of Type 1 diabetes mellitus. PMID- 26901604 TI - Evaluation of Device-associated Nosocomial Infections in a Paediatric Intensive Care Unit. AB - Objective: The aim of this study was to evaluate the rate of device-associated healthcare-associated infections (DA-HAI) in a paediatric intensive care unit (PICU). In addition, the identities of the responsible micro-organisms and of their antibiotic sensitivities were determined. Subjects and Methods: Patients who had been treated and followed-up in a PICU for more than 48 hours between January 2008 and December 2013 were included in the study. Device-associated nosocomial infections were defined by the Centers for Disease Control (CDC) criteria. Results: Nosocomial infections were detected in 244 of the 7376 patients over the six-year period. A diagnosis of DA-HAI was made in 75 (30.7%) of these infections. The rates of device utilization were 26% for mechanical ventilators, 6% for central venous catheters and 0.9% for urethral catheters. The rate of device-associated infections was 30.7%, and their frequency was 1.9/1000 patient-days. The device-associated nosocomial infection rates for mechanic ventilators, central and urethral catheters were 5.6, 1.62 and 3.77 per 1000 patient-days, respectively. Of these infections, Pseudomonas aeruginosa was the most frequent pathogen. Patients who developed hospital infections had longer durations of ICU hospitalizations and more often had to use mechanical ventilators and central and urinary catheters. Conclusions: The duration of hospitalization and the use of mechanical ventilators and central and urinary catheters were related to the increases in nosocomial infections. Therefore, target-oriented active surveillance should be regularly performed, and the superfluous employment of invasive devices should be avoided. PMID- 26901606 TI - The Issue of Leptospirosis in Grenada. AB - The aim of this study was to conduct a literature and secondary data review regarding leptospirosis and its impact in Grenada. The data analysed consisted of a published secondary source of animal investigations. The results of this investigation suggested that the burden of this disease is quite substantial and significant for the population of Grenada, as well as its global visitors. An examination into the literature related to public health policies and practices that could be suited to a developing nation like Grenada was then conducted. Recommendations were made regarding these analysed public health programmes revolving around surveillance, vector control, sanitation and education. PMID- 26901607 TI - Preseptal Cellulitis Or Orbital Cellulitis? AB - Preseptal cellulitis and orbital cellulitis can both present with increasing swelling, tenderness and redness around the eye, but their management differs. Preseptal cellulitis is more common and much less aggressive than orbital cellulitis. In contrast, orbital cellulitis is a medical emergency requiring urgent management. In this article, we provide a systematic approach to distinguish between preseptal cellulitis and orbital cellulitis at presentation, as the distinction between the two entities and the prompt recognition of orbital cellulitis can be potentially life-saving. PMID- 26901609 TI - Cleft Lip and Palate and Alveolar Bone Grafting in the United Kingdom: A Brief Overview for Non-specialists. AB - Cleft lip and palate is a common congenital defect that is associated with various functional, aesthetic and psychosocial problems. The objective of this article is to share a brief overview of cleft and lip palate classification, aetiology, complications and management, particularly aimed at non-specialists. The literature suggests that the use of iliac crest bone in secondary alveolar bone grafting (ABG) still seems to be the favoured technique for cleft lip and palate repair. In conclusion, we suggest that advances in bone morphogenic proteins may be the key to further advancement in ABG. PMID- 26901613 TI - Versican expression is an adverse prognostic factor in MLL-rearranged infant acute lymphoblastic leukaemia. PMID- 26901612 TI - Ligand-Dependent Conformational Dynamics of Dihydrofolate Reductase. AB - Enzymes are known to change among several conformational states during turnover. The role of such dynamic structural changes in catalysis is not fully understood. The influence of dynamics in catalysis can be inferred, but not proven, by comparison of equilibrium structures of protein variants and protein-ligand complexes. A more direct way to establish connections between protein dynamics and the catalytic cycle is to probe the kinetics of specific protein motions in comparison to progress along the reaction coordinate. We have examined the enzyme model system dihydrofolate reductase (DHFR) from Escherichia coli with tryptophan fluorescence-probed temperature-jump spectroscopy. We aimed to observe the kinetics of the ligand binding and ligand-induced conformational changes of three DHFR complexes to establish the relationship among these catalytic steps. Surprisingly, in all three complexes, the observed kinetics do not match a simple sequential two-step process. Through analysis of the relationship between ligand concentration and observed rate, we conclude that the observed kinetics correspond to the ligand binding step of the reaction and a noncoupled enzyme conformational change. The kinetics of the conformational change vary with the ligand's identity and presence but do not appear to be directly related to progress along the reaction coordinate. These results emphasize the need for kinetic studies of DHFR with highly specific spectroscopic probes to determine which dynamic events are coupled to the catalytic cycle and which are not. PMID- 26901614 TI - Programmed cell death-ligand 1 expression is associated with a favourable immune microenvironment and better overall survival in stage I pulmonary squamous cell carcinoma. AB - BACKGROUND: Programmed cell death-ligand 1 (PD-L1) is expressed in a subgroup of lung cancer that may benefit from immunotherapy. The interaction between PD-L1 expression and tumour infiltrating lymphocytes (TIL) remains poorly understood. This study investigated the expression of PD-L1 in surgically resected stage I pulmonary squamous cell carcinoma (SqCC) and correlated it with TILs in tumour microenvironments, common driver mutations, and clinical outcomes. MATERIALS AND METHODS: One hundred and five patients with surgically resected stage I squamous cell carcinoma were examined. Paraffin-embedded tumour sections were stained with PD-L1 antibody. Tumours with moderate-to-strong membrane staining in >= 5% of tumour cells were scored as positive for PD-L1 expression. The driver mutation epidermal growth factor receptor (EGFR), Kirsten rat sarcoma viral oncogene homolog (KRAS), and v-raf murine sarcoma viral oncogene homolog B (BRAF) were examined by direct sequencing, while anaplastic lymphoma kinase (ALK), phosphoinositide 3-kinase catalytic alpha (PI3KCA), and fibroblast growth factor receptor 1 (FGFR1) were analysed by immunohistochemistry. The correlations of PD L1 expression with each subtype of TIL, driver mutations, clinicopathologic parameters, and clinical outcomes were analysed. RESULTS: There was positive PD L1 expression in 56.2% (59/105) of patients. PD-L1 expression was not associated with the common clinicopathologic features and mutations of EGFR, KRAS, BRAF, ALK, PI3KCA, and FGFR1. As regards TILs composition, tumour PD-L1 expression was significantly associated with increased tumour epithelial CD8+ T cells and stromal CD4+ T cells. Otherwise, PD-L1 (+) tumour cells were negatively correlated with PD-L1 (+) immune cells within tumour stroma. By multivariate analysis, tumour PD-L1 expression and increased CD4+ T cell infiltrations in the tumour stroma were independent predictors of better overall survival and had a trend of better disease-free survival. CONCLUSIONS: PD-L1 expression is associated with a favourable immune microenvironment in stage I pulmonary SqCC and correlates with better clinical outcome. PMID- 26901615 TI - Emerging drugs for the treatment of Primary Biliary Cholangitis. AB - INTRODUCTION: Primary biliary cholangitis (PBC) is an autoimmune chronic disease of the liver that can progress to cirrhosis and hepatocellular carcinoma. It affects approximately 1 in 4,000 with a 10:1 female to male ratio. The diagnosis of PBC can be made based on serum antimitochondrial antibodies (AMA) in a patient with abnormally high serum alkaline phosphatase after ruling out other causes of cholestasis and biliary obstruction. Genome-wide association studies have revealed several human leukocyte antigen (HLA) and non-HLA risk loci in PBC, and complex environmental-host immunogenetic interactions are believed to underlie the etiopathogenesis of the disease. Fatigue and pruritus are the most common and often problematic symptoms; although often mild, these can be severe and life alternating in a subset of patients. Ursodeoxycholic acid (UDCA) is the only drug approved by the United States Food and Drug Administration for the treatment of PBC. Clinical trials have shown that UDCA significantly improves transplant-free survival. However, nearly 40% of PBC patients do not respond adequately to PBC and are at higher risk for serious complications when compared to PBC patients with complete response to UDCA. AREAS COVERED: Here we provide a detailed discussion regarding novel therapeutic agents and potential areas for further investigation in PBC-related research. EXPERT OPINION: Results of ongoing clinical trials and emerging treatment paradigms for PBC will likely further improve medical management of this disorder in the near future. PMID- 26901616 TI - Correction: Biochemical Monitoring of Spinal Cord Injury by FT-IR Spectroscopy Effects of Therapeutic Alginate Implant in Rat Models. PMID- 26901617 TI - Can the probability of radiation esophagitis be reduced without compromising lung tumor control: A radiobiological modeling study. PMID- 26901618 TI - Pneumococcal conjugate vaccine in adults: Let's see what happens. AB - The recent recommendation for the use of the 13-valent pneumococcal conjugate vaccine (PCV13) in adults 65 y of age and older, provides a new tool for preventing disease in this at-risk population. The conjugate vaccine induces a T cell dependent response, which distinguishes it from the polysaccharide vaccine and could provide the longer-term protection necessary to have a significant impact in this population. PMID- 26901619 TI - A Multidisciplinary Quality Improvement Approach Increases Breastmilk Availability at Discharge from the Neonatal Intensive Care Unit for the Very-Low Birth-Weight Infant. AB - BACKGROUND: Mothers of very-low-birth-weight (VLBW) infants often struggle to establish and maintain a milk supply. Children's Hospital of Orange County (CHOC Children's) data from 2005 to 2011 showed that while the total percentage of all neonatal intensive care unit (NICU) babies being discharged on breastmilk had remained stable, the percentage of VLBW babies with breastmilk at discharge had declined. This information resulted in a quality improvement initiative to remove barriers and implement programs shown to have the greatest impact on initiating and sustaining lactation in this patient subset. The objective of this initiative was to increase breastmilk availability at discharge for the VLBW population. MATERIALS AND METHODS: A multidisciplinary program was initiated, which included NICU parent and staff education, clarification of roles, and improved access to pumping supplies. Physicians and nurses completed online education. An algorithm defining roles in lactation support was developed, and a resource team of trained bedside nurses was formed. Lactation consultant time was then refocused on the VLBW population. In addition, "Lactation Support" was added to the physician daily documentation to bring the topic to daily bedside rounds. Twice weekly lactation rounds between the lactation consultant and neonatologist addressed lactation concerns for each dyad. To address pumping issues, the loaner pump program was enhanced. RESULTS: To assess the effectiveness of the initiative, breastmilk availability at discharge for the VLBW population at CHOC Children's was compared from baseline (2011) to the end of June 2015. VLBW breastmilk availability at discharge upon project initiation was 58.7% and increased by 36% to a final rate of 80% by 2013--a rate sustained through the first 6 months of 2015. CONCLUSIONS: The results of this initiative suggest that a multidisciplinary approach, including education, changes in workflow, and redefinition of roles, is effective in improving breastmilk rates at discharge in the VLBW patient population. PMID- 26901620 TI - Correction: A Simple Auxin Transcriptional Response System Regulates Multiple Morphogenetic Processes in the Liverwort Marchantia polymorpha. PMID- 26901621 TI - Comparison of French and Worldwide Bacillus anthracis Strains Favors a Recent, Post-Columbian Origin of the Predominant North-American Clade. AB - BACKGROUND: Bacillus anthracis, the highly dangerous zoonotic bacterial pathogen species is currently composed of three genetic groups, called A, B and C. Group A is represented worldwide whereas group B is present essentially in Western Europe and Southern Africa. Only three strains from group C have been reported. This knowledge is derived from the genotyping of more than 2000 strains collected worldwide. Strains from both group A and group B are present in France. Previous investigations showed that the majority of sporadic French strains belong to the so-called A.Br.011/009 group A clade and define a very remarkable polytomy with six branches. Here we explore the significance of this polytomy by comparing the French B. anthracis lineages to worldwide lineages. We take advantage of whole genome sequence data previously determined for 122 French strains and 45 strains of various origins. RESULTS: A total of 6690 SNPs was identified among the available dataset and used to draw the phylogeny. The phylogeny of the French B group strains which belongs to B.Br.CNEVA indicates an expansion from the south east part of France (the Alps) towards the south-west (Massif-Central and Pyrenees). The relatively small group A strains belonging to A.Br.001/002 results from at least two independent introductions. Strikingly, the data clearly demonstrates that the currently predominant B. anthracis lineage in North America, called WNA for Western North American, is derived from one branch of the A.Br.011/009 polytomy predominant in France. CONCLUSIONS/SIGNIFICANCE: The present work extends the range of observed substitution rate heterogeneity within B. anthracis, in agreement with its ecology and in contrast with some other pathogens. The population structure of the six branches A.Br.011/009 polytomy identified in France, diversity of branch length, and comparison with the WNA lineage, suggests that WNA is of post-Columbian and west European origin, with France as a likely source. Furthermore, it is tempting to speculate that the polytomy's most recent common ancestor -MRCA- dates back to the Hundred Years' war between France and England started in the mid-fourteenth century. These events were associated in France with deadly epidemics and major economic and social changes. PMID- 26901623 TI - Causes of Stranding and Mortality, and Final Disposition of Loggerhead Sea Turtles (Caretta caretta) Admitted to a Wildlife Rehabilitation Center in Gran Canaria Island, Spain (1998-2014): A Long-Term Retrospective Study. AB - AIMS: The aims of this study were to analyze the causes of stranding of 1,860 loggerhead turtles (Caretta caretta) admitted at the Tafira Wildlife Rehabilitation Center in Gran Canaria Island, Spain, from 1998 to 2014, and to analyze the outcomes of the rehabilitation process to allow meaningful auditing of its quality. METHODS: Primary causes of morbidity were classified into seven categories: entanglement in fishing gear and/or plastics, ingestion of hooks and monofilament lines, trauma, infectious disease, crude oil, other causes, and unknown/undetermined. Final dispositions were calculated as euthanasia (Er), unassisted mortality (Mr), and release (Rr) rates. Time to death (Td) for euthanized and dead turtles, and length of stay for released (Tr) turtles were evaluated. RESULTS: The most frequent causes of morbidity were entanglement in fishing gear and/or plastics (50.81%), unknown/undetermined (20.37%), and ingestion of hooks (11.88%). The final disposition of the 1,634 loggerhead turtles admitted alive were: Er = 3.37%, Mr = 10.34%, and Rr = 86.29%. Er was significantly higher in the trauma category (18.67%) compared to the other causes of admission. The highest Mr was observed for turtles admitted due to trauma (30.67%). The highest Rr was observed in the crude oil (93.87%) and entanglement (92.38%) categories. The median Tr ranged from 12 days (unknown) to 70 days (trauma). CONCLUSIONS: This survey is the first large-scale epidemiological study on causes of stranding and mortality of Eastern Atlantic loggerheads and demonstrates that at least 71.72% of turtles stranded due to anthropogenic causes. The high Rr (86.29%) emphasizes the importance of marine rehabilitation centers for conservation purposes. The stratified analysis by causes of admission of the three final disposition rates, and the parameters Td and Tr should be included in the outcome research of the rehabilitation process of sea turtles in order to allow comparative studies between marine rehabilitation centers around the world. PMID- 26901624 TI - Hybrid treatment of dysphagia lusoria: right carotid to subclavian bypass and endovascular insertion of an Amplatzer II Vascular Plug. AB - Compression of the esophagus by a retroesophageal aberrant right subclavian artery (ARSA) is a rare cause of dysphagia. We present the case of a 47-year-old female with symptoms of progressive dysphagia diagnosed with dysphagia lusoria using barium swallow and contrast computed tomography and successfully treated with a hybrid procedure: right carotid to subclavian bypass and endovascular insertion of an Amplatzer II Vascular Plug through the right superficial femoral artery. We consider this approach safer, less invasive and more complete to avoid recurrent dysphagia. PMID- 26901622 TI - Arsenophonus nasoniae and Rickettsiae Infection of Ixodes ricinus Due to Parasitic Wasp Ixodiphagus hookeri. AB - Arsenophonus nasoniae, a male-killing endosymbiont of chalcid wasps, was recently detected in several hard tick species. Following the hypothesis that its presence in ticks may not be linked to the direct occurrence of bacteria in tick's organs, we identified A. nasoniae in wasps emerging from parasitised nymphs. We confirmed that 28.1% of Ixodiphagus hookeri wasps parasitizing Ixodes ricinus ticks were infected by A. nasoniae. Moreover, in examined I. ricinus nymphs, A. nasoniae was detected only in those, which were parasitized by the wasp. However, in part of the adult wasps as well as in some ticks that contained wasp's DNA, we did not confirm A. nasoniae. We also found, that in spite of reported male-killing, some newly emerged adult wasp males were also infected by A. nasoniae. Additionally, we amplified the DNA of Rickettsia helvetica and Rickettsia monacensis (known to be Ixodes ricinus-associated bacteria) in adult parasitoid wasps. This may be related either with the digested bacterial DNA in wasp body lumen or with a role of wasps in circulation of rickettsiae among tick vectors. PMID- 26901625 TI - Enhanced-Resolution Optical Coherence Tomography Imaging. AB - PURPOSE: The effect of the enhanced-resolution imaging (ERI) technique on optical coherence tomography (OCT) images was evaluated. METHODS: A total of 5 healthy subjects and 20 patients diagnosed with various eye diseases were recruited into the study. ERI, a novel image processing technique, was accomplished by using super-resolution technology, and was assessed by objectively and subjectively comparing the image quality among three different image groups: images enlarged without bicubic interpolation (NONE), with bicubic interpolation (IP), and with ERI. RESULTS: ERI showed a higher ratio of the detailed variance to the background variance than NONE, whereas no significant difference was detected between NONE and IP. The mean opinion score of 5 experienced retinal specialists for ERI was significantly higher than that for IP. CONCLUSIONS: ERI generated a sharper image and clearly visualized small objects. Additionally, it is effective in enhancing OCT image quality. PMID- 26901626 TI - A Mn(II) complex of boradiazaindacene (BODIPY) loaded graphene oxide as both LED light and H2O2 enhanced anticancer agent. AB - Cancer cells are more susceptible to H2O2 induced cell death than normal cells. H2O2-activatable and O2-evolving nanoparticles could be used as photodynamic therapy agents in hypoxic environments. In this report, a photo-active Mn(II) complex of boradiazaindacene derivatives (Mn1) was used as a dioxygen generator under irradiation with LED light in water. Moreover, the in vitro biological evaluation for Mn1 and its loaded graphene oxide (herein called Mn1@GO) on HepG-2 cells in normal and hypoxic conditions has been performed. In particular, Mn1@GO can react with H2O2 resulting active anticancer species, which show high inhibition on both HepG-2 cells and CoCl2-treated HepG-2 cells (hypoxic cancer cells). The mechanism of LED light enhanced anticancer activity for Mn1@GO on HepG-2 cells was discussed. Our results show that Mn(II) complexes of boradiazaindacene (BODIPY) derivatives loaded GO can be both LED light and H2O2 activated anticancer agents in hypoxic environments. PMID- 26901627 TI - Protein-based ferrogels. AB - We present a novel synthesis in which hemoglobin and Fe(2+) react, in the presence of KNO3 and KOH, to produce protein microgels that contain magnetic iron oxide nanoparticles. The synthesis results in microgels with polymer properties (denaturing and glass transition temperatures) that are consistent with the dried protein. The iron oxide nanoparticles that exhibit an average diameter of 22nm, are ferrimagnetic, and display properties consistent with Fe3O4. The multiple functional capabilities displayed by these materials: biocompatibility, magnetism, dye uptake and controlled release, and other properties archetypal of hydrogels, will make the magnetic hydrogels attractive for a number of biomedical applications. PMID- 26901628 TI - Topoisomerase I inhibition and DNA cleavage by zinc, copper, and nickel derivatives of 2-[2-bromoethyliminomethyl]-4-[ethoxymethyl]phenol complexes exhibiting anti-proliferation and anti-metastasis activity. AB - Three transition metal derivatives (Zn, Cu, and Ni) of 2-[2 bromoethyliminomethyl]-4-[ethoxymethyl]phenol (L) were synthesized by the reaction of the metal salts with the Schiff base ligand in one pot. In the crystal structure of [Zn(L)Br], the Schiff base ligand binds to the metal center through its phenolate oxygen and imine nitrogen, and adopts a distorted tetrahedral geometry. These compounds were found to inhibit topoisomerase I (topo I) activity, induce DNA cleavage and show DNA binding activity. Moreover, these compounds were found to be cytotoxic towards several cancer cell lines (A2780, MCF-7, HT29, HepG2, A549, PC3, LNCaP) and prevent metastasis of PC3. Collectively, Cu(II) complex 2 shows superior activity relative to its Zn(II) and Ni(II) analogs. PMID- 26901629 TI - Unbound position II in MXCXXC metallochaperone model peptides impacts metal binding mode and reactivity: Distinct similarities to whole proteins. AB - The effect of position II in the binding sequence of copper metallochaperones, which varies between Thr and His, was investigated through structural analysis and affinity and oxidation kinetic studies of model peptides. A first Cys-Cu(I) Cys model obtained for the His peptide at acidic and neutral pH, correlated with higher affinity and more rapid oxidation of its complex; in contrast, the Thr peptide with the Cys-Cu(I)-Met coordination under neutral conditions demonstrated weaker and pH dependent binding. Studies with human antioxidant protein 1 (Atox1) and three of its mutants where S residues were replaced with Ala suggested that (a) the binding affinity is influenced more by the binding sequence than by the protein fold (b) pH may play a role in binding reactivity, and (c) mutating the Met impacted the affinity and oxidation rate more drastically than did mutating one of the Cys, supporting its important role in protein function. Position II thus plays a dominant role in metal binding and transport. PMID- 26901630 TI - Wavelength-Scale Structures as Extremely High Haze Films for Efficient Polymer Solar Cells. AB - Wavelength-scale inverted pyramid structures with low reflectance and excellent haze have been designed for application to polymer solar cells (PSCs). The wavelength-scale structured haze films are fabricated on the back surface of glass without damages to organic active layer by using a soft lithographic technique with etched GaN molds. With a rigorous coupled-wave analysis of optical modeling, we find the shift of resonance peaks with the increase of pattern's diameter. Wavelength-scale structures could provide the number of resonances at the long wavelength spectrum (lambda = 650-800 nm), yielding enhancement of power conversion efficiency (PCE) in the PSCs. Compared with a flat device (PCE = 7.12%, Jsc = 15.6 mA/cm(2)), improved PCE of 8.41% is achieved in a haze film, which is mainly due to the increased short circuit current density (Jsc) of 17.5 mA/cm(2). Hence, it opens up exciting opportunities for a variety of PSCs with wavelength-scale structures to further improve performance, simplify complicated process, and reduce costs. PMID- 26901632 TI - NMR-Based Chemosensing via p-H2 Hyperpolarization: Application to Natural Extracts. AB - When dealing with trace analysis of complex mixtures, NMR suffers from both low sensitivity and signal overlap. NMR chemosensing, in which the association between an analyte and a receptor is "signaled" by an NMR response, has been proposed as a valuable analytical tool for biofluids and natural extracts. Such chemosensors offer the possibility to simultaneously detect and distinguish different analytes in solution, which makes them particularly suitable for analytical applications on complex mixtures. In this study, we have combined NMR chemosensing with nuclear spin hyperpolarization. This was realized using an iridium complex as a receptor in the presence of parahydrogen: association of the target analytes to the metal center results in approximately 1000-fold enhancement of the NMR response. This amplification allows the detection, identification, and quantification of analytes at low-micromolar concentrations, provided they can weakly associate to the iridium chemosensor. Here, our NMR chemosensing approach was applied to the quantitative determination of several flavor components in methanol extracts of ground coffee. PMID- 26901631 TI - Motor Unit Characteristics after Targeted Muscle Reinnervation. AB - Targeted muscle reinnervation (TMR) is a surgical procedure used to redirect nerves originally controlling muscles of the amputated limb into remaining muscles above the amputation, to treat phantom limb pain and facilitate prosthetic control. While this procedure effectively establishes robust prosthetic control, there is little knowledge on the behavior and characteristics of the reinnervated motor units. In this study we compared the m. pectoralis of five TMR patients to nine able-bodied controls with respect to motor unit action potential (MUAP) characteristics. We recorded and decomposed high-density surface EMG signals into individual spike trains of motor unit action potentials. In the TMR patients the MUAP surface area normalized to the electrode grid surface (0.25 +/- 0.17 and 0.81 +/- 0.46, p < 0.001) and the MUAP duration (10.92 +/- 3.89 ms and 14.03 +/- 3.91 ms, p < 0.01) were smaller for the TMR group than for the controls. The mean MUAP amplitude (0.19 +/- 0.11 mV and 0.14 +/- 0.06 mV, p = 0.07) was not significantly different between the two groups. Finally, we observed that MUAP surface representation in TMR generally overlapped, and the surface occupied by motor units corresponding to only one motor task was on average smaller than 12% of the electrode surface. These results suggest that smaller MUAP surface areas in TMR patients do not necessarily facilitate prosthetic control due to a high degree of overlap between these areas, and a neural information-based control could lead to improved performance. Based on the results we also infer that the size of the motor units after reinnervation is influenced by the size of the innervating motor neuron. PMID- 26901635 TI - Fabrication of Hybrid Nanostructures via Nanoscale Laser-Induced Reshaping for Advanced Light Manipulation. AB - Ordered hybrid nanostructures for nanophotonics applications are fabricated by a novel approach via femtosecond laser melting of asymmetric metal-dielectric (Au/Si) nanoparticles created by lithographical methods. The approach allows selective reshaping of the metal components of the hybrid nanoparticles without affecting the dielectric ones and is applied for tuning of the scattering properties of the hybrid nanostructures in the visible range. PMID- 26901633 TI - Glucocorticoids Inhibit Basal and Hormone-Induced Serotonin Synthesis in Pancreatic Beta Cells. AB - Diabetes is a major complication of chronic Glucocorticoids (GCs) treatment. GCs induce insulin resistance and also inhibit insulin secretion from pancreatic beta cells. Yet, a full understanding of this negative regulation remains to be deciphered. In the present study, we investigated whether GCs could inhibit serotonin synthesis in beta cell since this neurotransmitter has been shown to be involved in the regulation of insulin secretion. To this aim, serotonin synthesis was evaluated in vitro after treatment with GCs of either islets from CD1 mice or MIN6 cells, a beta-cell line. We also explored the effect of GCs on the stimulation of serotonin synthesis by several hormones such as prolactin and GLP 1. We finally studied this regulation in islet in two in vivo models: mice treated with GCs and with liraglutide, a GLP1 analog, and mice deleted for the glucocorticoid receptor in the pancreas. We showed in isolated islets and MIN6 cells that GCs decreased expression and activity of the two key enzymes of serotonin synthesis, Tryptophan Hydroxylase 1 (Tph1) and 2 (Tph2), leading to reduced serotonin contents. GCs also blocked the induction of serotonin synthesis by prolactin or by a previously unknown serotonin activator, the GLP-1 analog exendin-4. In vivo, activation of the Glucagon-like-Peptide-1 receptor with liraglutide during 4 weeks increased islet serotonin contents and GCs treatment prevented this increase. Finally, islets from mice deleted for the GR in the pancreas displayed an increased expression of Tph1 and Tph2 and a strong increased serotonin content per islet. In conclusion, our results demonstrate an original inhibition of serotonin synthesis by GCs, both in basal condition and after stimulation by prolactin or activators of the GLP-1 receptor. This regulation may contribute to the deleterious effects of GCs on beta cells. PMID- 26901636 TI - Effect of Resorbable Collagen Plug on Bone Regeneration in Rat Critical-Size Defect Model. AB - OBJECTIVE: The purpose of this investigation was to examine the effect of resorbable collagen plug (RCP) on bone regeneration in rat calvarial critical size defects. METHODS: About 5-mm-diameter calvarial defects were created in forty 12-week-old male Sprague-Dawley rats and implanted with or without RCP. Animals were killed at 1, 2, 4, and 8 weeks postoperatively. After being killed, specimens were collected and subjected to micro-computed tomography (MUCT) and histological analysis. RESULTS: The MUCT showed a significant increase of newly formed bone volume/tissue volume in RCP-implanted defect compared with controls at all designated time points. After 8 weeks, the defects implanted with RCP displayed almost complete closure. Hematoxylin and eosin staining of the decalcified sections confirmed these observations and evidenced active bone regeneration in the RCP group. In addition, Masson's trichrome staining demonstrated that RCP implantation accelerated the process of collagen maturation. CONCLUSIONS: The RCP enhances bone regeneration in rat critical-size cranial defects, which suggest it might be a desired material for bone defect repair. PMID- 26901637 TI - Geography and Timing of Cases of Eastern Equine Encephalitis in New York State from 1992 to 2012. AB - INTRODUCTION: In New York State (NYS), Eastern equine encephalitis (EEE) was first reported in a human in 1971, in horses in 1970, and in pheasants in 1952. MATERIAL AND METHOD: Following work for the interval from 1970 to 1991, we identified cases in vertebrates from 1992 to 2012, through a passive surveillance system involving veterinarians in clinical practice, county health departments, and the Departments of Agriculture and Markets, Environmental Conservation, and Health, of the State of New York. RESULT: During an 11-year hiatus, from 1992 to 2002, no case in any vertebrate was observed. In a re-emergence, from 2003 to 2012, disease occurred in 12 counties, including 7 counties where disease had never been documented. Vertebrate cases included 4 cases in humans and 77 nonhuman occurrences; in 58 horses, Equus ferus caballus L.; 2 deer, Odocoileus virginianus Zimmermann; 6 dogs, Canis familiaris; 10 birds; and 1 flock of pheasants, Phasianus colchicus L. These were the first reported cases in NYS in white-tailed deer, the domestic dog, and in five species of birds: American crow, Corvus brachyrhynchos Brehm; American goldfinch, Carduelis tristis L.; bald eagle, Haliaeetus leucocephalus L.; blue jay, Cyanocitta cristata (L.); and red tailed hawk, Buteo jamaicensis Gmelin. One crow was dually infected with EEE virus and West Nile virus. The northern, southern, and southeastern borders of the state were newly affected. CONCLUSION: The geographic area, time periods, and vertebrate species with risk of EEE disease expanded from 1992 to 2012. PMID- 26901638 TI - Detection of 3-methylmethcathinone and its metabolites 3-methylephedrine and 3 methylnorephedrine in pubic hair samples by liquid chromatography-high resolution/high accuracy Orbitrap mass spectrometry. AB - Hair testing is considered to be one of the most efficient tool to investigate drug-related histories, particularly when the period of use needs to be tested back to many days or even months before sampling. High-resolution mass spectrometry represents today one of the most specific and sensitive analytical techniques to detect psychoactive substances in hair samples following single or multiple drug exposures. In this study pubic hair testing, by means of liquid chromatography-high resolution/high accuracy Orbitrap mass spectrometry, was employed to document the potential intake of five new psychoactive substances by a drug dealer. Pubic hair samples were decontaminated and pulverized with a ball mill, and, after the addition of the internal standard 3,4 methylenedioxypropylamphetamine, extracted with methanol:trifluoroacetic acid 9:1 at 45 degrees C for one night. The obtained extracts were analyzed on a Thermo Fisher Scientific Accela 1250 liquid chromatography system coupled to a Thermo Fisher Scientific single-stage Exactive HCD mass spectrometry system. 3 methylmethcathinone (3-MMC) was found to be present at a concentration of 25.8ng/mg in the pubic hair sample, whereas the other four designer drugs were found to be absent. 3-methylephedrines and 3-methylnorephedrines, metabolites of 3-MMC, were identified in the same sample, thereby proving the 3-MMC intake by the drug dealer. PMID- 26901639 TI - Demographics and post-mortem toxicology findings in deaths among people arrested multiple times for use of illicit drugs and/or impaired driving. AB - BACKGROUND: Multiple arrests for use of illicit drugs and/or impaired driving strongly suggests the existence of a personality disorder and/or a substance abuse problem. METHODS: This retrospective study (1993-2010) used a national forensic toxicology database (TOXBASE), and we identified 3943 individuals with two or more arrests for use of illicit drugs and/or impaired driving. These individuals had subsequently died from a fatal drug poisoning or some other cause of death, such as trauma. RESULTS: Of the 3943 repeat offenders 1807 (46%) died from a fatal drug overdose and 2136 (54%) died from other causes (p<0.001). The repeat offenders were predominantly male (90% vs 10%) and mean age of drug poisoning deaths was 5 y younger (mean 35 y) than other causes of death (mean 40 y). Significantly more repeat offenders (46%) died from drug overdose compared with all other forensic autopsies (14%) (p<0.001). Four or more drugs were identified in femoral blood in 44% of deaths from poisoning (drug overdose) compared with 18% of deaths by other causes (p<0.001). The manner of death was considered accidental in 54% of deaths among repeat offenders compared with 28% for other suspicious deaths (p<0.001). The psychoactive substances most commonly identified in autopsy blood from repeat offenders were ethanol, morphine (from heroin), diazepam, amphetamines, cannabis, and various opioids. CONCLUSIONS: This study shows that people arrested multiple times for use of illicit drugs and/or impaired driving are more likely to die by accidentally overdosing with drugs. Lives might be saved if repeat offenders were sentenced to treatment and rehabilitation for their drug abuse problem instead of conventional penalties for drug-related crimes. PMID- 26901640 TI - Designer cantilevers for even more accurate quantitative measurements of biological systems with multifrequency AFM. AB - Multifrequency excitation/monitoring of cantilevers has made it possible both to achieve fast, relatively simple, nanometre-resolution quantitative mapping of mechanical of biological systems in solution using atomic force microscopy (AFM), and single molecule resolution detection by nanomechanical biosensors. A recent paper by Penedo et al [2015 Nanotechnology 26 485706] has made a significant contribution by developing simple methods to improve the signal to noise ratio in liquid environments, by selectively enhancing cantilever modes, which will lead to even more accurate quantitative measurements. PMID- 26901641 TI - Strategies To Achieve Control over the Surface Ratio of Two Different Components on Modified Electrodes Using Aryldiazonium Salts. AB - Controlling the composition of an interface is very important in tuning the chemical and physical properties of a surface in many applications including biosensors, biomaterials, and chemical catalysis. Frequently, this requires one molecular component to a minor component in a mixed layer. Such subtle control of composition has been difficult to achieve using aryldiazonium salts. Herein, aryldiazonium salts of carboxyphenyl (CP) and phenylphosphorylcholine (PPC), generated in situ from their corresponding anilines, are electrografted to form molecular platform that are available for further functionalization. These two components are chosen because CP provides a convenient functionality for further coupling of biorecognition species while PPC offers resistance to nonspecific adsorption of proteins to the surface. Mixed layers of CP and PPC were prepared by grafting them either simultaneously or consecutively. The latter strategy allows an interface to be developed in a controlled way where one component is at levels of less than 1% of the total layer. PMID- 26901642 TI - Synthetic Transcription Amplifier System for Orthogonal Control of Gene Expression in Saccharomyces cerevisiae. AB - This work describes the development and characterization of a modular synthetic expression system that provides a broad range of adjustable and predictable expression levels in S. cerevisiae. The system works as a fixed-gain transcription amplifier, where the input signal is transferred via a synthetic transcription factor (sTF) onto a synthetic promoter, containing a defined core promoter, generating a transcription output signal. The system activation is based on the bacterial LexA-DNA-binding domain, a set of modified, modular LexA binding sites and a selection of transcription activation domains. We show both experimentally and computationally that the tuning of the system is achieved through the selection of three separate modules, each of which enables an adjustable output signal: 1) the transcription-activation domain of the sTF, 2) the binding-site modules in the output promoter, and 3) the core promoter modules which define the transcription initiation site in the output promoter. The system has a novel bidirectional architecture that enables generation of compact, yet versatile expression modules for multiple genes with highly diversified expression levels ranging from negligible to very strong using one synthetic transcription factor. In contrast to most existing modular gene expression regulation systems, the present system is independent from externally added compounds. Furthermore, the established system was minimally affected by the several tested growth conditions. These features suggest that it can be highly useful in large scale biotechnology applications. PMID- 26901643 TI - New Phylogenetic Groups of Torque Teno Virus Identified in Eastern Taiwan Indigenes. AB - Torque teno virus (TTV) is a single-stranded DNA virus highly prevalent in the world. It has been detected in eastern Taiwan indigenes with a low prevalence of 11% by using N22 region of which known to underestimate TTV prevalence excessively. In order to clarify their realistic epidemiology, we re-analyzed TTV prevalence with UTR region. One hundred and forty serum samples from eastern Taiwanese indigenous population were collected and TTV DNA was detected in 133 (95%) samples. Direct sequencing revealed an extensive mix-infection of different TTV strains within the infected individual. Entire TTV open reading frame 1 was amplified and cloned from a TTV positive individual to distinguish mix-infected strains. Phylogenetic analysis showed eleven isolates were clustered into a monophyletic group that is distinct from all known groups. In addition, another our isolate was clustered with recently described Hebei-1 strain and formed an independent clade. Based on the distribution pattern of pairwise distances, both new clusters were placed at phylogenetic group level, designed as the 6th and 7th phylogenetic group. In present study, we showed a very high prevalence of TTV infection in eastern Taiwan indigenes and indentified new phylogenetic groups from the infected individual. Both intra- and inter-phylogenetic group mix infections can be found from one healthy person. Our study has further broadened the field of human TTVs and proposed a robust criterion for classification of the major TTV phylogenetic groups. PMID- 26901644 TI - Functional Anatomy of Recognition of Chinese Multi-Character Words: Convergent Evidence from Effects of Transposable Nonwords, Lexicality, and Word Frequency. AB - This fMRI study aimed to identify the neural mechanisms underlying the recognition of Chinese multi-character words by partialling out the confounding effect of reaction time (RT). For this purpose, a special type of nonword transposable nonword-was created by reversing the character orders of real words. These nonwords were included in a lexical decision task along with regular (non transposable) nonwords and real words. Through conjunction analysis on the contrasts of transposable nonwords versus regular nonwords and words versus regular nonwords, the confounding effect of RT was eliminated, and the regions involved in word recognition were reliably identified. The word-frequency effect was also examined in emerged regions to further assess their functional roles in word processing. Results showed significant conjunctional effect and positive word-frequency effect in the bilateral inferior parietal lobules and posterior cingulate cortex, whereas only conjunctional effect was found in the anterior cingulate cortex. The roles of these brain regions in recognition of Chinese multi-character words were discussed. PMID- 26901645 TI - Association of TLR4 and Treg in Helicobacter pylori Colonization and Inflammation in Mice. AB - The host immune response plays an important role in the pathogenesis of Helicobacter pylori infection. The aim of this study was to clarify the immune pathogenic mechanism of Helicobacter pylori infection via TLR signaling and gastric mucosal Treg cells in mice. To discover the underlying mechanism, we selectively blocked the TLR signaling pathway and subpopulations of regulatory T cells in the gastric mucosa of mice, and examined the consequences on H. pylori infection and inflammatory response as measured by MyD88, NF-kappaB p65, and Foxp3 protein expression levels and the levels of Th1, Th17 and Th2 cytokines in the gastric mucosa. We determined that blocking TLR4 signaling in H. pylori infected mice decreased the numbers of Th1 and Th17 Treg cells compared to controls (P < 0.001-0.05), depressed the immune response as measured by inflammatory grade (P < 0.05), and enhanced H. pylori colonization (P < 0.05). In contrast, blocking CD25 had the opposite effects, wherein the Th1 and Th17 cell numbers were increased (P < 0.001-0.05), immune response was enhanced (P < 0.05), and H. pylori colonization was inhibited (P < 0.05) compared to the non-blocked group. In both blocked groups, the Th2 cytokine IL-4 remained unchanged, although IL-10 in the CD25 blocked group was significantly decreased (P < 0.05). Furthermore, MyD88, NF-kappaB p65, and Foxp3 in the non-blocked group were significantly lower than those in the TLR4 blocked group (P < 0.05), but significantly higher than those of the CD25 blocked group (P < 0.05). Together, these results suggest that there might be an interaction between TLR signaling and Treg cells that is important for limiting H. pylori colonization and suppressing the inflammatory response of infected mice. PMID- 26901646 TI - A Model for Improving the Learning Curves of Artificial Neural Networks. AB - In this article, the performance of a hybrid artificial neural network (i.e. scale-free and small-world) was analyzed and its learning curve compared to three other topologies: random, scale-free and small-world, as well as to the chemotaxis neural network of the nematode Caenorhabditis Elegans. One hundred equivalent networks (same number of vertices and average degree) for each topology were generated and each was trained for one thousand epochs. After comparing the mean learning curves of each network topology with the C. elegans neural network, we found that the networks that exhibited preferential attachment exhibited the best learning curves. PMID- 26901647 TI - Trans-Sacral Epiduroscopic Laser Decompression for Symptomatic Lumbar Disc Herniation: A Preliminary Case Series. AB - OBJECTIVE: The purpose of this study was to investigate the effect of trans sacral epiduroscopic laser decompression (SELD) in patients with a herniated lumbar disc. METHODS: This prospective case series study was designed to determine the outcomes of SELD with regard to reducing pain and improving the functional status in patients with low back pain (LBP) and radiculopathy caused by definitive neural compression confirmed by MRI. A total of 250 patients with LBP and simultaneous radiculopathy underwent SELD by applying a Ho:YAG laser. Clinical outcomes were evaluated using the visual analogue scale (VAS) score for LBP, and radiculopathy and functional status were measured using the Oswestry Disability Index (ODI). RESULTS: At 2 weeks after the procedure, the average VAS score for leg pain decreased to 3.6 from 7.1 (p < 0.01), and the average VAS score for back pain decreased to 4.1 from 5.9 (p < 0.01). At 3 months, the average VAS scores for leg and back pain decreased to 2.6 and 2.7, respectively. The mean ODI improved from 50 to 19 at 2 weeks postoperatively and further decreased to 12 at 3 months postoperatively. CONCLUSIONS: The VAS score and ODI significantly improved after SELD in herniated nucleus pulposus (HNP) patients with LBP and radiculopathy. Postoperative MRI showed a notable decrease in the HNP size and a reduction in neural compression. SELD is suggested to be an effective therapeutic modality for patients with symptomatic HNP. PMID- 26901649 TI - Analysis of computational footprinting methods for DNase sequencing experiments. AB - DNase-seq allows nucleotide-level identification of transcription factor binding sites on the basis of a computational search of footprint-like DNase I cleavage patterns on the DNA. Frequently in high-throughput methods, experimental artifacts such as DNase I cleavage bias affect the computational analysis of DNase-seq experiments. Here we performed a comprehensive and systematic study on the performance of computational footprinting methods. We evaluated ten footprinting methods in a panel of DNase-seq experiments for their ability to recover cell-specific transcription factor binding sites. We show that three methods--HINT, DNase2TF and PIQ--consistently outperformed the other evaluated methods and that correcting the DNase-seq signal for experimental artifacts significantly improved the accuracy of computational footprints. We also propose a score that can be used to detect footprints arising from transcription factors with potentially short residence times. PMID- 26901651 TI - Multiple Sclerosis Epidemiology in East Asia, South East Asia and South Asia: A Systematic Review. AB - BACKGROUND: Multiple sclerosis (MS) is one of the most common chronic immune mediated diseases of the human central nervous system and an important cause of non-traumatic neurologic disability among young population in several countries. Recent reports from East Asia, South East Asia and South Asia have proposed a low to moderate prevalence of MS in these countries. METHODS: A literature review search was carried out in December 2014 in Medline, Embase, Scopus and Cochrane library to recover original population-based studies on MS epidemiology in East Asia, South East Asia and South Asia countries published between January 1, 1950 and December 30, 2014. We intended search strategies using the key words: multiple sclerosis, prevalence, incidence and epidemiology. Based on our inclusion criteria, 68 epidemiologic studies were included in this systematic review. RESULTS: The most extensively used diagnostic criteria in the studies were McDonald's criteria. Most studies were performed in a multi-center hospital setting. The female to male ratio varied and ranged from 0.7 in India to 9.0 in China. The mean age at disease onset ranged from the lowest age of 25.3 in Iran to the highest age of 46.4 in China. MS prevalence ranged from 0.77 in 100,000 populations in Hong Kong (1999) to 85.80 in 100,000 in Iran (2013). CONCLUSIONS: Advances in MS registries around the globe allow nationwide population-based studies and will allow worldly comparisons between the prevalence and incidence in different regions that are provided to monitor estimation. PMID- 26901650 TI - High-resolution mass spectrometry of small molecules bound to membrane proteins. AB - Small molecules are known to stabilize membrane proteins and to modulate their function and oligomeric state, but such interactions are often hard to precisely define. Here we develop and apply a high-resolution, Orbitrap mass spectrometry based method for analyzing intact membrane protein-ligand complexes. Using this platform, we resolve the complexity of multiple binding events, quantify small molecule binding and reveal selectivity for endogenous lipids that differ only in acyl chain length. PMID- 26901652 TI - On the Kaolinite Floc Size at the Steady State of Flocculation in a Turbulent Flow. AB - The flocculation of cohesive fine-grained sediment plays an important role in the transport characteristics of pollutants and nutrients absorbed on the surface of sediment in estuarine and coastal waters through the complex processes of sediment transport, deposition, resuspension and consolidation. Many laboratory experiments have been carried out to investigate the influence of different flow shear conditions on the floc size at the steady state of flocculation in the shear flow. Most of these experiments reported that the floc size decreases with increasing shear stresses and used a power law to express this dependence. In this study, we performed a Couette-flow experiment to measure the size of the kaolinite floc through sampling observation and an image analysis system at the steady state of flocculation under six flow shear conditions. The results show that the negative correlation of the floc size on the flow shear occurs only at high shear conditions, whereas at low shear conditions, the floc size increases with increasing turbulent shear stresses regardless of electrolyte conditions. Increasing electrolyte conditions and the initial particle concentration could lead to a larger steady-state floc size. PMID- 26901648 TI - Inferring causal molecular networks: empirical assessment through a community based effort. AB - It remains unclear whether causal, rather than merely correlational, relationships in molecular networks can be inferred in complex biological settings. Here we describe the HPN-DREAM network inference challenge, which focused on learning causal influences in signaling networks. We used phosphoprotein data from cancer cell lines as well as in silico data from a nonlinear dynamical model. Using the phosphoprotein data, we scored more than 2,000 networks submitted by challenge participants. The networks spanned 32 biological contexts and were scored in terms of causal validity with respect to unseen interventional data. A number of approaches were effective, and incorporating known biology was generally advantageous. Additional sub-challenges considered time-course prediction and visualization. Our results suggest that learning causal relationships may be feasible in complex settings such as disease states. Furthermore, our scoring approach provides a practical way to empirically assess inferred molecular networks in a causal sense. PMID- 26901655 TI - A DFT-Elucidated Comparison of the Solution-Phase and SAM Electrochemical Properties of Short-Chain Mercaptoalkylferrocenes: Synthetic and Spectroscopic Aspects, and the Structure of Fc-CH2CH2-S-S-CH2CH2-Fc. AB - Facile synthetic procedures to synthesize a series of difficult-to-obtain mercaptoalkylferrocenes, namely, Fc(CH2)nSH, where n = 1 (1), 2 (2), 3 (3), or 4 (4) and Fc = Fe(eta(5)-C5H5)(eta(5)-C5H4), are reported. Dimerization of 1-4 to the corresponding disulfides 19-22 was observed in air. Dimer 20 (Z = 2) crystallized in the triclinic space group P1. Dimers 20-22 could be reduced back to the original Fc(CH2)nSH derivatives with LiAlH4 in refluxing tetrahydrofuran. Density functional theory (DFT) calculations showed that the highest occupied molecular orbital of 1-4 lies exclusively on the ferrocenyl group implying that the electrochemical oxidation observed at ca. -15 < Epa < 76 mV versus FcH/FcH(+) involves exclusively an Fe(II) to Fe(III) process. Further DFT calculations showed this one-electron oxidation is followed by proton loss on the thiol group to generate a radical, Fc(CH2)nS(*), with spin density mainly located on the sulfur. Rapid exothermic dimerization leads to the observed dimers, Fc(CH2)n-S-S (CH 2)nFc. Reduction of the ferrocenium groups on the dimer occurs at potentials that still showed the ferrocenyl group DeltaE = Epa,monomer - Epc,dimer <= 78 mV, indicating that the redox properties of the ferrocenyl group on the mercaptans are very similar to those of the dimer. (1)H NMR measurements showed that, like ferrocenyl oxidation, the resonance position of the sulfhydryl proton, SH, and others, are dependent on -(CH2)n- chain length. Self-assembled monolayers (SAMs) on gold were generated to investigate the electrochemical behavior of 1-4 in the absence of diffusion. Under these conditions, DeltaE approached 0 mV for the longer chain derivatives at slow scan rates. The surface-bound ferrocenyl group of the metal-thioether, Fc(CH2)n -S-Au, is oxidized at approximately equal potentials as the equivalent CH2Cl2-dissolved ferrocenyl species 1-4. Surface coverage by the SAMs is dependent on alkyl chain length with the largest coverage obtained for 4, while the rate of heterogeneous electron transfer between SAM substrate and electrode was the fastest for the shortest chain derivative, Fc-CH2 S-Au. PMID- 26901654 TI - Mechanism(S) Involved in the Colon-Specific Expression of the Thiamine Pyrophosphate (Tpp) Transporter. AB - Microbiota of the large intestine synthesizes considerable amount of vitamin B1 (thiamine) in the form of thiamine pyrophosphate (TPP). We have recently demonstrated the existence of an efficient and specific carrier-mediated uptake process for TPP in human colonocytes, identified the TPP transporter (TPPT) involved (product of the SLC44A4 gene), and shown that expression of TPPT along the gastrointestinal (GI) tract is restricted to the colon. Our aim in this study was to determine the molecular basis of the colon-specific expression of TPPT focusing on a possible epigenetic mechanism. Our results showed that the CpG island predicted in the SLC44A4 promoter is non-methylated in the human colonic epithelial NCM460 cells, but is hyper-methylated in the human duodenal epithelial HuTu80 cells (as well as in the human retinal pigment epithelial ARPE19 cells). In the mouse (where TPPT expression in the GI tract is also restricted to the colon), the CpG island predicted in the Slc44a4 promoter is non-methylated in both the jejunum and colon, thus arguing against possible contribution of DNA methylation in the colon-specific expression of TPPT. A role for histone modifications in the tissue-specific pattern of Slc44a4 expression, however, was suggested by the findings that in mouse colon, histone H3 in the 5'-regulatory region of Slc44a4 is tri-methylated at lysine 4 and acetylated at lysine 9, whereas the tri-methylation at lysine 27 modification was negligible. In contrast, in the mouse jejunum, histone H3 is hyper-trimethylated at lysine 27 (repressor mark). Similarly, possible involvement of miRNA(s) in the tissue specific expression of TPPT was also suggested by the findings that the 3'-UTR of SLC44A4 is targeted by specific miRNAs/RNA binding proteins in non-colonic, but not in colonic, epithelial cells. These studies show, for the first time, epigenetic mechanisms (histone modifications) play a role in determining the tissue-specific pattern of expression of TPPT in the GI tract. PMID- 26901653 TI - SB203580 Modulates p38 MAPK Signaling and Dengue Virus-Induced Liver Injury by Reducing MAPKAPK2, HSP27, and ATF2 Phosphorylation. AB - Dengue virus (DENV) infection causes organ injuries, and the liver is one of the most important sites of DENV infection, where viral replication generates a high viral load. The molecular mechanism of DENV-induced liver injury is still under investigation. The mitogen activated protein kinases (MAPKs), including p38 MAPK, have roles in the hepatic cell apoptosis induced by DENV. However, the in vivo role of p38 MAPK in DENV-induced liver injury is not fully understood. In this study, we investigated the role of SB203580, a p38 MAPK inhibitor, in a mouse model of DENV infection. Both the hematological parameters, leucopenia and thrombocytopenia, were improved by SB203580 treatment and liver transaminases and histopathology were also improved. We used a real-time PCR microarray to profile the expression of apoptosis-related genes. Tumor necrosis factor alpha, caspase 9, caspase 8, and caspase 3 proteins were significantly lower in the SB203580 treated DENV-infected mice than that in the infected control mice. Increased expressions of cytokines including TNF-alpha, IL-6 and IL-10, and chemokines including RANTES and IP-10 in DENV infection were reduced by SB203580 treatment. DENV infection induced the phosphorylation of p38MAPK, and its downstream signals including MAPKAPK2, HSP27 and ATF-2. SB203580 treatment did not decrease the phosphorylation of p38 MAPK, but it significantly reduced the phosphorylation of MAPKAPK2, HSP27, and ATF2. Therefore, SB203580 modulates the downstream signals to p38 MAPK and reduces DENV-induced liver injury. PMID- 26901656 TI - 38 years of autopsy findings in South African mine workers. AB - BACKGROUND: South African miners have a statutory right to autopsies for occupational lung disease compensation. These autopsies also provide information for research and surveillance. METHODS: Cardio-respiratory organs are removed where miners die and are examined at the National Institute for Occupational Health. We extracted data from the PATHAUT database and described key demographic, exposure and disease trends (1975-2013). RESULTS: Of 109,101 autopsies, 72,348 (66.3%) were black, and 34,794 (31.9%) were white miners. Autopsies declined from over 3,000 (1975-1998) to 1,118 in 2013. Most were gold miners (74.0%). 78.6% black and 13.2% white miners died while in employment. Overall proportions of silicosis and pulmonary tuberculosis were 12.0% and 13.0% in black, and 20.5% and 2.4% in white miners, respectively. Disease increased over time. CONCLUSIONS: High levels of disease persist. Black ex-miners are underrepresented, indicating a need for strategies to improve awareness and provision of autopsy facilities in labor-sending areas. PMID- 26901657 TI - Barriers to access and participation in community mental health treatment for anxious children. AB - BACKGROUND: Anxiety disorders are the most common psychiatric disorders among children in the United States; yet many children do not receive treatment due to barriers to treatment access and participation. This study examined common barriers to treatment access and participation among anxious children who participated in computer-assisted cognitive behavioral therapy. Differences in barriers reported by treatment completers/non-completers were examined, as was the association with sociodemographic characteristics, anxiety severity, and impairment. The impact of barriers on treatment response was assessed, as well as the relationship with treatment expectancy and satisfaction. METHOD: Barriers to access and participation, demographics, anxiety severity/impairment, treatment credibility and satisfaction were assessed among parents and children with anxiety (N=100; ages 7-13) who were enrolled in a community-based randomized clinical trial. RESULTS: The most common access barrier was parents not knowing where or from whom to seek services (66%). Differences among completers and non completers were related to stigma, confidentiality, and costs. The most common parent-reported barrier to participating was stress (32.4%) and child-reported barrier to participation was not having enough time to complete homework (22.1%). Of the sociodemographic, clinical and treatment characteristics, minority status, satisfaction, and treatment response were associated with barriers to treatment participation, although these associations varied by barriers related to treatment and external factors. LIMITATIONS: Cross sectional design and lack of well-established psychometric properties for barriers measures were limitations. CONCLUSION: Findings suggest that accessible, time-efficient, cost-effective service delivery methods that minimize stigma and maximize engagement when delivering evidence-based treatment for pediatric anxiety are needed. PMID- 26901658 TI - Charge Carrier Lifetimes Exceeding 15 MUs in Methylammonium Lead Iodide Single Crystals. AB - The charge carrier lifetime in organic-inorganic perovskites is one of the most important parameters for modeling and design of solar cells and other types of devices. In this work, we use CH3NH3PbI3 single crystal as a model system to study optical absorption, charge carrier generation, and recombination lifetimes. We show that commonly applied photoluminescence lifetime measurements may dramatically underestimate the intrinsic carrier lifetime in CH3NH3PbI3, which could be due to severe charge recombination at the crystal surface and/or fast electron-hole recombination close to the surface. By using the time-resolved microwave conductivity technique, we investigated the lifetime of free mobile charges inside the crystals. Most importantly, we find that for homogeneous excitation throughout the crystal, the charge carrier lifetime exceeds 15 MUs. This means that the diffusion length in CH3NH3PbI3 can be as large as 50 MUm if it is no longer limited by the dimensions of the crystallites. PMID- 26901659 TI - Synthesis and Optical Properties of Lead-Free Cesium Tin Halide Perovskite Nanocrystals. AB - Metal halide perovskite crystal structures have emerged as a class of optoelectronic materials, which combine the ease of solution processability with excellent optical absorption and emission qualities. Restricting the physical dimensions of the perovskite crystallites to a few nanometers can also unlock spatial confinement effects, which allow large spectral tunability and high luminescence quantum yields at low excitation densities. However, the most promising perovskite structures rely on lead as a cationic species, thereby hindering commercial application. The replacement of lead with nontoxic alternatives such as tin has been demonstrated in bulk films, but not in spatially confined nanocrystals. Here, we synthesize CsSnX3 (X = Cl, Cl0.5Br0.5, Br, Br0.5I0.5, I) perovskite nanocrystals and provide evidence of their spectral tunability through both quantum confinement effects and control of the anionic composition. We show that luminescence from Sn-based perovskite nanocrystals occurs on pico- to nanosecond time scales via two spectrally distinct radiative decay processes, which we assign to band-to-band emission and radiative recombination at shallow intrinsic defect sites. PMID- 26901660 TI - Social workers as care coordinators: Leaders in ensuring effective, compassionate care. AB - The concept of care coordination is at the forefront of national conversations in the context of health care reform. As pediatric social workers, we are interested in how care coordination benefits our patients, and which disciplines are providing coordination services. We have determined that significant overlap exists between the work social workers are already doing in inpatient and outpatient medical settings and the literature's definition of care coordination activities. This article outlines our process of literature review and creation of a working definition of care coordination, and frames the concepts we believe remain central to the process of care coordination. PMID- 26901661 TI - An Active Type I-E CRISPR-Cas System Identified in Streptomyces avermitilis. AB - CRISPR-Cas systems, the small RNA-dependent immune systems, are widely distributed in prokaryotes. However, only a small proportion of CRISPR-Cas systems have been identified to be active in bacteria. In this work, a naturally active type I-E CRISPR-Cas system was found in Streptomyces avermitilis. The system shares many common genetic features with the type I-E system of Escherichia coli, and meanwhile shows unique characteristics. It not only degrades plasmid DNA with target protospacers, but also acquires new spacers from the target plasmid DNA. The naive features of spacer acquisition in the type I-E system of S. avermitilis were investigated and a completely conserved PAM 5'-AAG 3' was identified. Spacer acquisition displayed differential strand bias upstream and downstream of the priming spacer, and irregular integrations of new spacers were observed. In addition, introduction of this system into host conferred phage resistance to some extent. This study will give new insights into adaptation mechanism of the type I-E systems in vivo, and meanwhile provide theoretical foundation for applying this system on the genetic modification of S. avermitilis. PMID- 26901663 TI - Inferring Stop-Locations from WiFi. AB - Human mobility patterns are inherently complex. In terms of understanding these patterns, the process of converting raw data into series of stop-locations and transitions is an important first step which greatly reduces the volume of data, thus simplifying the subsequent analyses. Previous research into the mobility of individuals has focused on inferring 'stop locations' (places of stationarity) from GPS or CDR data, or on detection of state (static/active). In this paper we bridge the gap between the two approaches: we introduce methods for detecting both mobility state and stop-locations. In addition, our methods are based exclusively on WiFi data. We study two months of WiFi data collected every two minutes by a smartphone, and infer stop-locations in the form of labelled time intervals. For this purpose, we investigate two algorithms, both of which scale to large datasets: a greedy approach to select the most important routers and one which uses a density-based clustering algorithm to detect router fingerprints. We validate our results using participants' GPS data as well as ground truth data collected during a two month period. PMID- 26901662 TI - Sterol Carrier Protein-2, a Nonspecific Lipid-Transfer Protein, in Intracellular Cholesterol Trafficking in Testicular Leydig Cells. AB - Sterol carrier protein-2 (SCP2), also called nonspecific lipid-transfer protein, is thought to play a major role in intracellular lipid transport and metabolism, and it has been associated with diseases involving abnormalities in lipid trafficking, such as Zellweger syndrome. The Scp2 gene encodes the 58 kDa sterol carrier protein-x (SCPX) and 15 kDa pro-SCP2 proteins, both of which contain a 13 kDa SCP2 domain in their C-termini. We found that 22-NBD-cholesterol, a fluorescent analog of cholesterol and a preferred SCP2 ligands, was not localized in the peroxisomes. This raises questions about previous reports on the localization of the SCPX and SCP2 proteins and their relationship to peroxisomes and mitochondria in intracellular cholesterol transport. Immunofluorescent staining of cryosections of mouse testis and of MA-10 mouse tumor Leydig cells showed that SCPX and SCP2 are present in both mouse testicular interstitial tissue and in MA-10 cells. Fluorescent fusion proteins of SCPX and SCP2, as well as confocal live-cell imaging, were used to investigate the subcellular targeting of these proteins and the function of the putative mitochondrial targeting sequence. The results showed that SCPX and SCP2 are targeted to the peroxisomes by the C-terminal PTS1 domain, but the putative N-terminal mitochondrial targeting sequence alone is not potent enough to localize SCPX and SCP2 to the mitochondria. Homology modeling and molecular docking studies indicated that the SCP2 domain binds cholesterol, but lacks specificity of the binding and/or transport. These findings further our understanding of the role of SCPX and SCP2 in intracellular cholesterol transport, and present a new point of view on the role of these proteins in cholesterol trafficking. PMID- 26901665 TI - 1,2-Ethanediol and 1,3-Propanediol Conversions over (MO3)3 (M = Mo, W) Nanoclusters: A Computational Study. AB - The dehydration and dehydrogenation reactions of one and two 1,2-ethanediol and 1,3-propanediol molecules on (MO3)3 (M = Mo, W) nanoclusters have been studied computationally using density functional and coupled cluster (CCSD(T)) theory. The reactions are initiated by the formation of a Lewis acid-base complex with an additional hydrogen bond. Dehydration is the dominant reaction proceeding via a metal bisdiolate. Acetaldehyde, the major product for 1,2-ethanediol, is produced by alpha-hydrogen transfer from one CH2 group to the other. For 1,3-propanediol, the C-C bond breaking pathways to produce C2H4 and HCH?O simultaneously and proton transfer to generate propylene oxide have comparable barrier energies. The barrier to produce propanal from the propylene oxide complex is less than that for epoxide release from the cluster. On the Mo3O9 cluster, a redox reaction channel for 1,2-ethanediol to break the C-C bond to form two formaldehyde molecules and then to produce C2H4 is slightly more favorable than the formation of acetaldehyde. For W(VI), the energy barrier for the reduction pathway is larger due to the lower reducibility of W3O9. Similar reduction on Mo(VI) for 1,3 propanediol to form propene is not a favorable pathway compared with the other pathways as additional C-H bond breaking is required in addition to breaking a C C bond. The dehydrogenation and dehydration activation energies for the selected glycols are larger than the reactions of ethanol and 1-propanol on the same clusters. The CCSD(T) method is required because density functional theory with the M06 and B3LYP functionals does not predict quantitative energies on the potential energy surface. The M06 functional performs better than does the B3LYP functional. PMID- 26901664 TI - The Effect of an Acute Bout of Moderate-Intensity Aerobic Exercise on Motor Learning of a Continuous Tracking Task. AB - INTRODUCTION: There is evidence for beneficial effects of acute and long-term exercise interventions on several forms of memory, including procedural motor learning. In the present study we examined how performing a single bout of continuous moderate intensity aerobic exercise would impact motor skill acquisition and retention in young healthy adults, compared to a period of rest. We hypothesized that exercise would improve motor skill acquisition and retention, compared to motor practice alone. MATERIALS AND METHODS: Sixteen healthy adults completed sessions of aerobic exercise or seated rest that were immediately followed by practice of a novel motor task (practice). Exercise consisted of 30 minutes of continuous cycling at 60% peak O2 uptake. Twenty-four hours after practice, we assessed motor learning with a no-exercise retention test (retention). We also quantified changes in offline motor memory consolidation, which occurred between practice and retention (offline). Tracking error was separated into indices of temporal precision and spatial accuracy. RESULTS: There were no differences between conditions in the timing of movements during practice (p = 0.066), at retention (p = 0.761), or offline (p = 0.966). However, the exercise condition enabled participants to maintain spatial accuracy during practice (p = 0.477); whereas, following rest performance diminished (p = 0.050). There were no significant differences between conditions at retention (p = 0.532) or offline (p = 0.246). DISCUSSION: An acute bout of moderate-intensity aerobic exercise facilitated the maintenance of motor performance during skill acquisition, but did not influence motor learning. Given past work showing that pairing high intensity exercise with skilled motor practice benefits learning, it seems plausible that intensity is a key modulator of the effects of acute aerobic exercise on changes in complex motor behavior. Further work is necessary to establish a dose-response relationship between aerobic exercise and motor learning. PMID- 26901666 TI - Design and Synthesis of Benzimidazoles As Novel Corticotropin-Releasing Factor 1 Receptor Antagonists. AB - Benzazole derivatives with a flexible aryl group bonded through a one-atom linker as a new scaffold for a corticotropin-releasing factor 1 (CRF1) receptor antagonist were designed, synthesized, and evaluated. We expected that structural diversity could be expanded beyond that of reported CRF1 receptor antagonists. In a structure-activity relationship study, 4-chloro-N(2)-(4-chloro-2-methoxy-6 methylphenyl)-1-methyl-N(7),N(7)-dipropyl-1H-benzimidazole-2,7-diamine 29g had the most potent binding activity against a human CRF1 receptor and the antagonistic activity (IC50 = 9.5 and 88 nM, respectively) without concerns regarding cytotoxicity at 30 MUM. Potent CRF1 receptor-binding activity in brain in an ex vivo test and suppression of stress-induced activation of the hypothalamus-pituitary-adrenocortical (HPA) axis were also observed at 138 MUmol/kg of compound 29g after oral administration in mice. Thus, the newly designed benzimidazole 29g showed in vivo CRF1 receptor antagonistic activity and good brain penetration, indicating that it is a promising lead for CRF1 receptor antagonist drug discovery research. PMID- 26901667 TI - The efficiency of peptide immunotherapy for respiratory allergy. AB - Allergen immunotherapy (AIT) was introduced more than a century ago and is yet the only disease-modifying treatment for allergy. AIT is currently conducted with whole allergen extracts and several studies clearly support its efficacy in the treatment of respiratory allergies, however the need for a long treatment - that affects costs and patients compliance - and possible IgE-mediated adverse events are still unresolved issues. Peptide immunotherapy is based on the use of short synthetic peptides which represent major T-cell epitopes of the allergen with markedly reduced ability to cross-link IgE and activate mast cells and basophils. Data from clinical trials confirmed the efficacy and tolerability of peptide immunotherapy in patients with cat allergy, with a sustained clinical effect after a short course treatment. Peptide therapy is a promising safe and effective new specific treatment for allergy to be developed for the most important allergens causing rhinitis or asthma. PMID- 26901668 TI - TRPM3 gating in planar lipid bilayers defines peculiar agonist specificity. PMID- 26901669 TI - Acoustic Plate Mode sensing in liquids based on free and electrically shorted plate surfaces. AB - The sensing behavior to liquids for Acoustic Plate Modes (APMs) propagating along 64 degrees Y, 90 degrees X LiNbO3 plate was investigated vs. two electric boundary conditions. The changes in the APMs phase velocity and attenuation were measured upon exposure to different liquids wetting one of the surfaces of the plate, either free or electrically shorted by a thin conductive Al layer. The experimental data confirm that the presence of a metallic layer covering one of the plate surfaces affects the viscosity and temperature sensitivity of the device. The differences between the sensor response for various liquids, with free or metalized faces, are interpreted in terms of the APM polarization. PMID- 26901670 TI - Novel frameshift mutation in the CHD7 gene associated with CHARGE syndrome with preaxial polydactyly. PMID- 26901672 TI - Latest options for treatment of bronchiolitis in infants. AB - Bronchiolitis is the most frequent pathology associated with lower respiratory tract infection in newborns and young infants. The treatment of bronchiolitis is essentially supportive therapy for respiratory distress, hypoxia and dehydration. To date, no specific antiviral drug is used on a routine basis for the treatment of RSV infections. Currently, the only antiviral drug approved for the infection is ribavirin; however, its use is limited due to adverse side effects and the risks it poses to healthcare providers. Moreover, several drugs have been routinely administered for years in infants with acute RSV bronchiolitis, even if their efficacy is often not confirmed by clinical evidence, and studies on emerging antiviral drugs are still ongoing. In the present paper we review the recent literature about the drugs used during acute bronchiolitis and we summarize the main recommendations of national and international guidelines and the latest options for the treatment of bronchiolitis. PMID- 26901671 TI - Run of homozygosity analysis reveals a novel nonsense variant of the CNGB1 gene involved in retinitis pigmentosa 45. PMID- 26901673 TI - Atraumatic skin sparing mastectomy flap retraction for internal mammary vessel dissection in autologous breast reconstruction. PMID- 26901674 TI - Correction: Optic Disc Change during Childhood Myopic Shift: Comparison between Eyes with an Enlarged Cup-To-Disc Ratio and Childhood Glaucoma Compared to Normal Myopic Eyes. PMID- 26901675 TI - Pharmaco-EEG Studies in Animals: A History-Based Introduction to Contemporary Translational Applications. AB - Current research on the effects of pharmacological agents on human neurophysiology finds its roots in animal research, which is also reflected in contemporary animal pharmaco-electroencephalography (p-EEG) applications. The contributions, present value and translational appreciation of animal p-EEG-based applications are strongly interlinked with progress in recording and neuroscience analysis methodology. After the pioneering years in the late 19th and early 20th century, animal p-EEG research flourished in the pharmaceutical industry in the early 1980s. However, around the turn of the millennium the emergence of structurally and functionally revealing imaging techniques and the increasing application of molecular biology caused a temporary reduction in the use of EEG as a window into the brain for the prediction of drug efficacy. Today, animal p EEG is applied again for its biomarker potential - extensive databases of p-EEG and polysomnography studies in rats and mice hold EEG signatures of a broad collection of psychoactive reference and test compounds. A multitude of functional EEG measures has been investigated, ranging from simple spectral power and sleep-wake parameters to advanced neuronal connectivity and plasticity parameters. Compared to clinical p-EEG studies, where the level of vigilance can be well controlled, changes in sleep-waking behaviour are generally a prominent confounding variable in animal p-EEG studies and need to be dealt with. Contributions of rodent pharmaco-sleep EEG research are outlined to illustrate the value and limitations of such preclinical p-EEG data for pharmacodynamic and chronopharmacological drug profiling. Contemporary applications of p-EEG and pharmaco-sleep EEG recordings in animals provide a common and relatively inexpensive window into the functional brain early in the preclinical and clinical development of psychoactive drugs in comparison to other brain imaging techniques. They provide information on the impact of drugs on arousal and sleep architecture, assessing their neuropharmacological characteristics in vivo, including central exposure and information on kinetics. In view of the clear disadvantages as well as advantages of animal p-EEG as compared to clinical p EEG, general statements about the usefulness of EEG as a biomarker to demonstrate the translatability of p-EEG effects should be made with caution, however, because they depend on the particular EEG or sleep parameter that is being studied. The contribution of animal p-EEG studies to the translational characterisation of centrally active drugs can be furthered by adherence to guidelines for methodological standardisation, which are presently under construction by the International Pharmaco-EEG Society (IPEG). PMID- 26901676 TI - DNA Copy Number Aberrations, and Human Papillomavirus Status in Penile Carcinoma. Clinico-Pathological Correlations and Potential Driver Genes. AB - Penile squamous cell carcinoma is a rare disease, in which somatic genetic aberrations have yet to be characterized. We hypothesized that gene copy aberrations might correlate with human papillomavirus status and clinico pathological features. We sought to determine the spectrum of gene copy number aberrations in a large series of PSCCs and to define their correlations with human papillomavirus, histopathological subtype, and tumor grade, stage and lymph node status. Seventy formalin-fixed, paraffin embedded penile squamous cell carcinomas were centrally reviewed by expert uropathologists. DNA was extracted from micro-dissected samples, subjected to PCR-based human papillomavirus assessment and genotyping (INNO-LiPA human papillomavirus Genotyping Extra Assay) and microarray-based comparative genomic hybridization using a 32K Bacterial Artificial Chromosome array platform. Sixty-four samples yielded interpretable results. Recurrent gains were observed in chromosomes 1p13.3-q44 (88%), 3p12.3 q29 (86%), 5p15.33-p11 (67%) and 8p12-q24.3 (84%). Amplifications of 5p15.33-p11 and 11p14.1-p12 were found in seven (11%) and four (6%) cases, respectively. Losses were observed in chromosomes 2q33-q37.3 (86%), 3p26.3-q11.1 (83%) and 11q12.2-q25 (81%). Although many losses and gains were similar throughout the cohort, there were small significant differences observed at specific loci, between human papillomavirus positive and negative tumors, between tumor types, and tumor grade and nodal status. These results demonstrate that despite the diversity of genetic aberrations in penile squamous cell carcinomas, there are significant correlations between the clinico-pathological data and the genetic changes that may play a role in disease natural history and progression and highlight potential driver genes, which may feature in molecular pathways for existing therapeutic agents. PMID- 26901677 TI - Mating-Induced Transcriptome Changes in the Reproductive Tract of Female Aedes aegypti. AB - The Aedes aegypti mosquito is a significant public health threat, as it is the main vector of dengue and chikungunya viruses. Disease control efforts could be enhanced through reproductive manipulation of these vectors. Previous work has revealed a relationship between male seminal fluid proteins transferred to females during mating and female post-mating physiology and behavior. To better understand this interplay, we used short-read RNA sequencing to identify gene expression changes in the lower reproductive tract of females in response to mating. We characterized mRNA expression in virgin and mated females at 0, 6 and 24 hours post-mating (hpm) and identified 364 differentially abundant transcripts between mating status groups. Surprisingly, 60 transcripts were more abundant at 0 hpm compared to virgin females, suggesting transfer from males. Twenty of these encode known Ae. aegypti seminal fluid proteins. Transfer and detection of male accessory gland-derived mRNA in females at 0 hpm was confirmed by measurement of eGFP mRNA in females mated to eGFP-expressing males. In addition, 150 transcripts were up-regulated at 6 hpm and 24 hpm, while 130 transcripts were down-regulated at 6 hpm and 24 hpm. Gene Ontology (GO) enrichment analysis revealed that proteases, a protein class broadly known to play important roles in reproduction, were among the most enriched protein classes. RNAs associated with immune system and antimicrobial function were also up-regulated at 24 hpm. Collectively, our results suggest that copulation initiates broad transcriptome changes across the mosquito female reproductive tract, "priming" her for important subsequent processes of blood feeding, egg development and immune defense. Our transcriptome analysis provides a vital foundation for future studies of the consequences of mating on female biology and will aid studies seeking to identify specific gene families, molecules and pathways that support key reproductive processes in the female mosquito. PMID- 26901679 TI - Comparison of clinical trial versus non-clinical trial treatment outcomes of childhood acute lymphoblastic leukemia using comparable regimens. AB - OBJECTIVES: Treatment regimens tested in major clinical trials, conducted by cooperative groups, are often adapted as standard of care by cancer centers with the hope to replicate the treatment outcomes reported in these landmark studies. It is therefore postulated that applying clinical trial regimens in a non clinical trial setting yield similar outcomes. The aim of the present study was to explore this hypothesis in the context of childhood acute lymphoblastic leukemia (ALL) in our institution. METHODS: We retrospectively evaluated 224 consecutive pediatric ALL cases treated between January 2001 and December 2007. Standard-risk (SR) patients were treated on CCG-1991 (regimen OD) while high-risk (HR) patients were treated on CCG-1961 (regimen D). Results were compared with those of the equivalent regimen in the original clinical trials. Statistical analysis was carried using chi-square or Fisher's exact test, Kaplan-Meier and log-rank tests. RESULTS: Comparison of treatment outcomes revealed that SR patients had inferior 5-year overall survival (OS) of (89.0 +/- 2.9 vs. 96.0% +/- 0.9%); event-free survival of (82.3 +/- 3.5 vs. 88.7% +/- 1.4%); and relapse rate of (15.8 vs. 9.3% (P = 0.034)) compared to patients treated in the clinical trial. However, no statistically significant difference in treatment outcomes was observed between HR patients. CONCLUSIONS: Despite using comparable regimens, suboptimal outcomes were noted in SR patients implying that similar treatments do not necessarily yield similar outcomes. This underscores the need to evaluate outcomes of adapted regimens to identify areas that need further improvement in centers not enrolling patients on prospective collaborative clinical trials. PMID- 26901680 TI - Gaussian Mixture Models of Between-Source Variation for Likelihood Ratio Computation from Multivariate Data. AB - In forensic science, trace evidence found at a crime scene and on suspect has to be evaluated from the measurements performed on them, usually in the form of multivariate data (for example, several chemical compound or physical characteristics). In order to assess the strength of that evidence, the likelihood ratio framework is being increasingly adopted. Several methods have been derived in order to obtain likelihood ratios directly from univariate or multivariate data by modelling both the variation appearing between observations (or features) coming from the same source (within-source variation) and that appearing between observations coming from different sources (between-source variation). In the widely used multivariate kernel likelihood-ratio, the within source distribution is assumed to be normally distributed and constant among different sources and the between-source variation is modelled through a kernel density function (KDF). In order to better fit the observed distribution of the between-source variation, this paper presents a different approach in which a Gaussian mixture model (GMM) is used instead of a KDF. As it will be shown, this approach provides better-calibrated likelihood ratios as measured by the log likelihood ratio cost (Cllr) in experiments performed on freely available forensic datasets involving different trace evidences: inks, glass fragments and car paints. PMID- 26901681 TI - Oral Administration of Pregabalin in Rats before or after Nerve Injury Partially Prevents Spontaneous Neuropathic Pain and Long Outlasts the Treatment Period. AB - BACKGROUND AND METHODS: Pregabalin alleviates stimulus-evoked neuropathic pain (NeuP) in some pain patients and rodents in models of painful neuropathies. But it is not known if pregabalin can also alleviate spontaneous NeuP. Sciatic and saphenous neurectomy in rats elicits spontaneous self-mutilation of the denervated hindpaw, a behavior that models spontaneous NeuP. We tested if pregabalin (20 or 30 mg/kg/day; twice daily, per os) for 7 days before denervation, or 42 days thereafter, can suppress this behavior. RESULTS: Compared with the vehicle, pregabalin administered in both treatment regimens markedly and significantly delayed autotomy onset and suppressed its levels for weeks after treatment cessation. CONCLUSIONS: At doses known to effectively suppress stimulus evoked pain in rats, pregabalin can prevent development of spontaneous NeuP and suppress it postoperatively. PMID- 26901678 TI - Fluorescent Polymer Nanoparticles Based on Dyes: Seeking Brighter Tools for Bioimaging. AB - Speed, resolution and sensitivity of today's fluorescence bioimaging can be drastically improved by fluorescent nanoparticles (NPs) that are many-fold brighter than organic dyes and fluorescent proteins. While the field is currently dominated by inorganic NPs, notably quantum dots (QDs), fluorescent polymer NPs encapsulating large quantities of dyes (dye-loaded NPs) have emerged recently as an attractive alternative. These new nanomaterials, inspired from the fields of polymeric drug delivery vehicles and advanced fluorophores, can combine superior brightness with biodegradability and low toxicity. Here, we describe the strategies for synthesis of dye-loaded polymer NPs by emulsion polymerization and assembly of pre-formed polymers. Superior brightness requires strong dye loading without aggregation-caused quenching (ACQ). Only recently several strategies of dye design were proposed to overcome ACQ in polymer NPs: aggregation induced emission (AIE), dye modification with bulky side groups and use of bulky hydrophobic counterions. The resulting NPs now surpass the brightness of QDs by ~10-fold for a comparable size, and have started reaching the level of the brightest conjugated polymer NPs. Other properties, notably photostability, color, blinking, as well as particle size and surface chemistry are also systematically analyzed. Finally, major and emerging applications of dye-loaded NPs for in vitro and in vivo imaging are reviewed. PMID- 26901682 TI - Time Series Modelling of Syphilis Incidence in China from 2005 to 2012. AB - BACKGROUND: The infection rate of syphilis in China has increased dramatically in recent decades, becoming a serious public health concern. Early prediction of syphilis is therefore of great importance for heath planning and management. METHODS: In this paper, we analyzed surveillance time series data for primary, secondary, tertiary, congenital and latent syphilis in mainland China from 2005 to 2012. Seasonality and long-term trend were explored with decomposition methods. Autoregressive integrated moving average (ARIMA) was used to fit a univariate time series model of syphilis incidence. A separate multi-variable time series for each syphilis type was also tested using an autoregressive integrated moving average model with exogenous variables (ARIMAX). RESULTS: The syphilis incidence rates have increased three-fold from 2005 to 2012. All syphilis time series showed strong seasonality and increasing long-term trend. Both ARIMA and ARIMAX models fitted and estimated syphilis incidence well. All univariate time series showed highest goodness-of-fit results with the ARIMA(0,0,1)*(0,1,1) model. CONCLUSION: Time series analysis was an effective tool for modelling the historical and future incidence of syphilis in China. The ARIMAX model showed superior performance than the ARIMA model for the modelling of syphilis incidence. Time series correlations existed between the models for primary, secondary, tertiary, congenital and latent syphilis. PMID- 26901683 TI - Risk of hospitalization due to pneumococcal disease in adults in Spain. The CORIENNE study. AB - Pneumococcal disease causes a high burden of disease in adults, leading to high rates of hospitalization, especially in the elderly. All hospital discharges for pneumococcal disease and pneumococcal pneumonia among adults over 18 y of age reported in first diagnostic position in 2011 (January 1, 2011 through December 31, 2011) were obtained. A total of 10,861 hospital discharges due to pneumococcal disease were reported in adults in Spain in 2011 with an annual incidence of hospitalization of 0.285 (CI 95%: 0.280-0.291) per 1,000 population over 18 y old. Case-fatality rate was 8%. Estimated cost of these hospitalisations in 2011 was more than 57 million ?. Pneumococcal pneumonia accounted for the 92% of the hospital discharges All the chronic condition studied: asplenia, chronic respiratory disease, chronic heart disease, chronic renal disease, Diabetes Mellitus and immunosuppression, increased the risk of hospitalization in patients with pneumococcal pneumonia, especially in those aged 18-64 y old. Case-fatality rate among adult patients hospitalized with at least one underlying condition was significantly higher than among patients without comorbidities. Our results identified asplenia, chronic respiratory disease, chronic heart disease, chronic renal disease, chronic liver disease, Diabetes Mellitus and immunosuppression as risk groups for hospitalization. Older adults, immunocompromised patients and immunocompetent patients with underlying conditions could benefit from vaccination. PMID- 26901684 TI - Immunization against TGF-beta1 reduces collagen deposition but increases sustained inflammation in a murine asthma model. AB - Transforming growth factor (TGF)-beta1 is involved in the processes of airway inflammation and remodeling; however, its reported roles in asthma pathogenesis are controversial. We sought both to investigate the effects of active immunization targeting TGF-beta1 on allergen-induced airway inflammatory responses and to evaluate its possible application for asthma treatment. BALB/c mice were immunized with a virus-like-particle (VLP) vaccine presenting a TGF beta1 peptide. For the preventive intervention of acute allergic airway inflammation, immunization was conducted before sensitization and challenges with ovalbumin (OVA), and for the therapeutic treatment of chronic inflammatory responses, immunization was initiated after inflammatory responses were established. Preventive immunization with VLPs led to increased proinflammatory IL-4, IL-13, and IL-33 levels in the bronchoalveolar lavage fluids (BALF) with no significant effects on lung tissue inflammation and airway goblet cell hyperplasia. Therapeutic treatment showed that at 24 h after the fourth 2-day challenge with OVA following 2 intraperitoneal sensitizations, airway subepithelial collagen deposition was significantly ameliorated in vaccinated mice, whereas the lung histology and cytokine profile in the BALF were not changed. In contrast, after a 4-week recovery from the last OVA challenge, the vaccinated mice's collagen deposition remained reduced, but they sustained lung tissue inflammation and goblet-cell hyperplasia; elevated IL-13, TNF, and IFN gamma levels in the BALF; and increased airway resistance, tissue resistance, and tissue elastance. In a conclusion, the role of TGF-beta1 is complicated in allergic airway inflammatory responses. It is important to make a careful assessment in accordance with specific disease conditions when targeting TGF beta1 for a therapeutic purpose. PMID- 26901686 TI - White adipose tissue urea cycle activity is not affected by one-month treatment with a hyperlipidic diet in female rats. AB - Under high-energy diets, amino acid N is difficult to dispose of, as a consequence of the availability of alternative substrates. We found, recently, that WAT contains a complete functional urea cycle, we analyzed the possible overall changes in the WAT urea cycle (and other-related amino acid metabolism gene expressions) in rats subjected to a cafeteria diet. Adult female Wistar rats were fed control or simplified cafeteria diets. Samples of WAT sites: mesenteric, periovaric, retroperitoneal and subcutaneous, were used for the estimation of all urea cycle enzyme activities and gene expressions. Other key amino acid metabolism gene expressions, and lactate dehydrogenase were also measured. Subcutaneous WAT showed a differentiated amino acid metabolism profile, since its cumulative (whole site) activity for most enzymes was higher than the activities of the other sites studied. After one month of eating an energy-rich cafeteria diet, and in spite of doubling the size of WAT, the transforming capacity of most amino acid metabolism enzymes remained practically unchanged in the tissue. This was not only due to limited changes in the overall enzyme activity, but also a consequence of a relative decrease in the expression of the corresponding genes. Overall, the results of this study support the consideration of WAT as an organ, disperse but under uniform control. The metabolic peculiarities between its different sites, and their ability to adapt to different energy availability conditions only add to the variable nature of adipose tissue. We have presented additional evidence of the significant role of WAT in amino acid metabolism. PMID- 26901685 TI - A reagentless DNA-based electrochemical silver(I) sensor for real time detection of Ag(I) - the effect of probe sequence and orientation on sensor response. AB - Ag(I) is known to interact with cytosine (C) via the formation C-Ag(I)-C complexes. The authors have utilized this concept to design six electrochemical Ag(I) sensors using C-rich DNA probes. Alternating current voltammetry and cyclic voltammetry were used to analyze the sensors. The results show that the dual probe sensors that require the use of both 5'- and 3'-thiolated DNA probes are not suitable for this application, the differences in probe orientation impedes formation of C-Ag(I)-C complexes. Sensors fabricated with DNA probes containing both thymine (T) and C, independent of the location of the alkanethiol linker, do not response to Ag(I) either; T-T mismatches destabilize the duplex even in the presence of Ag(I). However, sensors fabricated with DNA probes containing both adenine (A) and C are ideal for this application, owing to the formation of C Ag(I)-C complexes, as well as other lesser known interactions between A and Ag(I). Both sensors are sensitive, specific and selective enough to be used in 50% human saliva. They can also be used to detect silver sulfadiazine, a commonly prescribed antimicrobial drug. With further optimization, this sensing strategy may offer a promising approach for detection of Ag(I) in environmental and clinical samples. PMID- 26901687 TI - Analysis of dental students' written peer feedback from a prospective peer assessment protocol. AB - INTRODUCTION: Peer assessment and feedback is encouraged to enhance students' learning. The aim of this study was to quantitatively and qualitatively analyse pre-clinical and clinical dental students' written peer feedback provided as part of a continuous, formative and structured peer assessment protocol. MATERIALS AND METHODS: A total of 309 Year-2 and Year-5 dental students were invited to participate in a peer assessment and peer feedback protocol. Consenting volunteer students were trained to observe each other whilst working in the skills laboratory (Year-2) and in the dental clinic (Year-5). Subsequently, they followed a structured protocol of peer assessment and peer feedback using specially designed work-based forms during a complete academic year. The content of their written feedback was coded according to the UK General Dental Council domain, sign (positive or negative), specificity (task specific or general), and grouped into themes. RESULTS: A total of 108 participants (40 Year-2 and 68 Year 5) completed 1169 peer assessment work-based forms (516 pre-clinical and 653 clinical); 94% contained written feedback. The large majority (82%) of Year-2 feedback represented the clinical domain, 89% were positive, 77% were task specific, and they were grouped into 14 themes. Year-5 feedback was related mostly to Management and Leadership (37%) and Communication (32%), 64% were positive, 75% task specific, and they were clustered into 24 themes. DISCUSSION: The content of the feedback showed notable differences between Year-2 and Year-5 students. Senior students focused more on Communication and Management and Leadership skills, whilst juniors were more concerned with clinical skills. Year 5 students provided 13% negative feedback compared to only 2% from Year-2. Regulatory focus theory is discussed to explain these differences. Both groups provided peer feedback on a wide and different range of themes. However, four themes emerged in both groups: efficiency, infection control, time management and working speed. CONCLUSION: A structured peer assessment framework can be used to guide pre-clinical and clinical students to provide peer feedback focused on different domains, and on contrasting signs and specificities. It can also present an opportunity to complement tutors' feedback. PMID- 26901688 TI - [Introduction. Editorial announcement]. PMID- 26901689 TI - [Sentinel node biopsy and axillary clearence in early breast cancer--An algorithm with explanations and queries]. AB - The introduction of sentinel lymph node biopsy in early breast cancer patients has substantially changed the approach to axillary management traditionally consisting of lymph node dissection. It has also rendered it more sophisticated. Several factors influence the decision on whether a patient should be offered sentinel lymph node biopsy or axillary lymph node dissection after the biopsy or instead of it. The potential options have been combined into an algorithm, of which each step is explained with the most important evidences in support or against summarized. PMID- 26901690 TI - [Laparoscopic removal of large spleens: Pfannenstiel incision as an alternative specimen extraction method]. AB - BACKGROUND: Removing the extremely enlarged spleen from the abdominal cavity is a common technical problem in case of laparoscopic splenectomy ( LS). In general, the specimen is placed into a plastic bag and removed after morcellation. In case of massive splenomegaly , when the spleen weight is 1000-2000 grams, this method is often not feasible, because the spleen size is larger than the maximum capacity of the EndoBag. According to the literature in this case the splenic extraction was performed by specimen fragmentation in the abdominal cavity (risk of splenosis) or by a laparotomy. To solve this problem our team removes the specimen via a Pfannenstiel incision since 2009. METHODS: Between January 1, 2002 and September 30, 2014, 74 LS procedures were performed at our department. The specimen was retrieved with morcellation in a conventional manner through the lateral port site in 56 cases, whereas in 12 cases, the large spleen was retrieved through a 10-12 cm long Pfannenstiel incision. RESULTS: The mean duration of surgery was 121 (50-220) minutes. In those cases where the specimen was retrieved through a Pfannenstiel incision the mean duration of surgery was significantly shorter (108 vs. 125 minutes; p=0.05), and the mean spleen size was significantly larger (1032 vs. 338 grams; p=0.0001) than in the case of morcellation. In the duration of the mean postoperative hospital stay there was no significant difference (4.7 vs. 5.2 days; p=0.178). CONCLUSION: Our study supports that laparoscopic splenectomy is safe and has numerous advantages even in the case of massive splenomegaly. The retrieval of the specimen through a Pfannenstiel incision is considered a safe and cosmetically acceptable alternative. PMID- 26901691 TI - [Technical questions of the transrectal specimen extraction]. AB - INTRODUCTION: During laparoscopic partial colectomy the specimen can be extracted transrectally. This technique decreases the invasiveness of the surgery, because the abdominal wall incision is avoided. Premises of a new surgical technique are precise technical description as well as a favourable balance of advantages and disadvantages. In this paper the authors review the technique they apply and analyse their first results. PATIENTS AND METHOD: 45 laparoscopic bowel resections were performed by a multidisciplinary team between 16th April 2014 and 1st November 2015. Indication of surgery was endometriosis, and the specimen was extracted transrectally in 11 patients. Having ligated both bowel ends proximal and distal to the section infiltrated with endometriosis, and the proximal bowel secured with a laparoscopic bulldog. Then the bowel was resected and the specimen was extracted in a camera bag transrectally. A purse-string suture was placed into the proximal bowel end, and the anvil of the circular stapler--which was introduced transrectally--was inserted into the bowel. After closing the rectal stump, the anastomosis was performed with a circular stapler. We used this technique when the upper third of the rectum or sigmoid colon was infiltrated with endometriosis. RESULTS: The difference between the operation time of the two techniques (transabdominal vs. transrectal specimen extraction: 108 min vs. 118 min) was not significant. There was not difference in the WBC count between the first and second postoperative day, and there was not any anastomosis leakage detected either. CONCLUSION: By using the above technique, postoperative infections could have been reduced to minimum. Transrectal specimen extraction did not increase postoperative complication The authors believe this is a safe way of specimen extraction after partial colectomy. PMID- 26901692 TI - [Fulminant isolated necrotizing fasciitis of the chest wall, complicating thoracic empyema]. AB - Authors introduce the case of a 64-year-old male patient with fulminant isolated necrotizing fasciitis of the chest wall, complicating empyema thoracis of unknown origin. The patient's co-morbidities were hypertension, ischaemic heart disease, atrial fibrillation with oral anticoagulation. The real etiology was revealed post mortem, due to the rapid progression. The autopsy demonstrated that the fasciitis was caused by a small blunt thoracic trauma (haematoma), not emerged from patient's history and was not visible during physical examination. Authors review diagnostic pitfalls, leading to delayed recognition in addition to this very case. After quick diagnosis surgical debridement, targeted wide spectrum antibiotics and maximal intensive care are the basic pillars of the management of necrotizing fasciitis. PMID- 26901695 TI - Nanoghosts as a Novel Natural Nonviral Gene Delivery Platform Safely Targeting Multiple Cancers. AB - Nanoghosts derived from mesenchymal stem cells and retaining their unique surface associated tumor-targeting capabilities were redesigned as a selective and safe universal nonviral gene-therapy platform. pDNA-loaded nanoghosts efficiently targeted and transfected diverse cancer cells, in vitro and in vivo, in subcutaneous and metastatic orthotopic tumor models, leading to no adverse effects. Nanoghosts loaded with pDNA encoding for a cancer-toxic gene inhibited the growth of metastatic orthotopic lung cancer and subcutaneous prostate cancer models and dramatically prolonged the animals' survival. PMID- 26901696 TI - Discriminant factors for adolescent sexual offending: On the usefulness of considering both victim age and sibling incest. AB - Understanding the pathways and circumstances of juvenile sexual offending is of utmost importance. However, juvenile sexual offenders (JSO) represent an especially diverse group of individuals, and several categorizations have been proposed to obtain more homogeneous subgroups. Victim age-based and family relation-based categorizations are particularly promising because they seem theoretically and clinically relevant. Empirical results however are still inconsistent, and most studies have not considered these two dimensions jointly. The first goal of this study was to further examine the value of subgrouping JSO according to the age of their victim. A second goal was to determine the supplementary value, if any, of considering sibling incest. Based on a sample of 351 male JSO, it was first confirmed that sexual abuse of children was more strongly related to asociality (social skill deficits) than sexual abuse of peers, the latter being more closely associated with antisociality (general delinquency). The relevance of considering mixed-type JSO (with both child and peer victims) separately was also confirmed. More importantly, multivariate statistical analyses demonstrated that adding sibling incest to the equation was useful. JSO of intra-familial child were significantly more likely to have been victimized during their own childhood compared to JSO with extra-familial victims. Nevertheless, adolescents who had committed sibling incest obtained middle ground results on most variables (except for crime severity), suggesting that they constitute a distinct but not extreme, subgroup. This study confirmed the utility of using both the age and the family relation with the victim in characterizing juvenile sexual offending. PMID- 26901697 TI - The potential influence of the microbiota and probiotics on women during long spaceflights. AB - Humans have been exploring space for almost 55 years but space travel comes with many psychological and physiological changes that astronauts have to adapt to, both during and post flight missions. Now, with the reality of such missions lasting years, maintaining proper health of the flight crew is a high priority. While conditions such as nausea, bone loss, renal calculi and depression have been recognized, and approaches to medical and surgical care in space considered, the influence of the microbiota could be of added significance in maintaining astronaut health. While probiotics have long been part of the Russian cosmonaut diet, their use for specific health concerns of women has not been assessed. In this article, we explore the ways in which the microbiome may influence the health of female astronauts during long space flights, and present a rationale for the use of probiotics. PMID- 26901699 TI - The Role of Conformational Changes in Molecular Recognition. AB - Conformational changes of molecules are crucial elements in many biochemical processes, and also in molecular recognition. Here, we present a novel exact mathematical equation for the binding free energy of a receptor-ligand pair. It shows that the energetic contribution due to conformational changes upon molecular recognition is defined by the so-called Kullback-Leibler (KL) divergence between the probability distributions of the conformational ensemble of the biomolecule in the bound and free states. We show that conformational changes always contribute positively to the change in free energy and therefore disfavor the association process. Using the example of ligands binding to a flexible cavity of T4 lysozyme, we illustrate that, due to enthalpy-entropy compensation, the conformational entropy is a misleading quantity for assessing the conformational contribution to the binding free energy, in contrast to the KL divergence, which is the correct quantity to use in this context. PMID- 26901698 TI - Albumin and apolipoprotein H mRNAs in human plasma as potential clinical biomarkers of liver injury: analyses of plasma liver-specific mRNAs in patients with liver injury. AB - CONTEXT: Plasma liver-specific mRNAs are useful biomarkers of hepatotoxicity in rats. OBJECTIVE: To investigate the potential application of liver-specific mRNAs as biomarkers for liver injury in humans. METHODS: We determined the plasma levels of liver-specific mRNAs by real-time qRT-PCR in healthy donors and patients with liver injury. RESULTS: Plasma levels of albumin (ALB) and apolipoprotein H (APOH) mRNAs increased in patients with elevated serum alanine aminotransferase. These mRNAs also increased in plasma after transcatheter arterial chemoembolization, which induces specific injury to liver. CONCLUSIONS: We demonstrated the potential application of plasma ALB and APOH mRNAs as clinical biomarkers for liver injury. PMID- 26901700 TI - Effects of Graphene Nanopetal Outgrowths on Internal Thermal Interface Resistance in Composites. AB - Thermal resistance at the interface between fiber and matrix is often the determining factor influencing thermal transport in carbon fiber composites. Despite its significance, few experimental measurements of its magnitude have been performed to date. Here, a 3omega method is applied to measure the interfacial thermal resistance between individual carbon fibers and an epoxy matrix. The method incorporates bulk and interfacial regions to extract interfacial characteristics. Measured values indicate an average thermal interface resistance of 18 mm(2) K/W for an interface between bare fiber and epoxy, but the average value drops to 3 mm(2) K/W after a microwave plasma chemical vapor deposition of two-dimensional graphene nanopetals on the carbon fiber surface. PMID- 26901702 TI - Medullar toxicity after prolonged nitrous oxide exposure: an unexpected cause of bone marrow failure post allogeneic transplant. PMID- 26901701 TI - Impact of Delftia tsuruhatensis and Achromobacter xylosoxidans on Escherichia coli dual-species biofilms treated with antibiotic agents. AB - Recently it was demonstrated that for urinary tract infections species with a lower or unproven pathogenic potential, such as Delftia tsuruhatensis and Achromobacter xylosoxidans, might interact with conventional pathogenic agents such as Escherichia coli. Here, single- and dual-species biofilms of these microorganisms were characterized in terms of microbial composition over time, the average fitness of E. coli, the spatial organization and the biofilm antimicrobial profile. The results revealed a positive impact of these species on the fitness of E. coli and a greater tolerance to the antibiotic agents. In dual species biofilms exposed to antibiotics, E. coli was able to dominate the microbial consortia in spite of being the most sensitive strain. This is the first study demonstrating the protective effect of less common species over E. coli under adverse conditions imposed by the use of antibiotic agents. PMID- 26901703 TI - Hematopoietic stem cell transplantation activity worldwide in 2012 and a SWOT analysis of the Worldwide Network for Blood and Marrow Transplantation Group including the global survey. AB - Data on 68 146 hematopoietic stem cell transplants (HSCTs) (53% autologous and 47% allogeneic) gathered by 1566 teams from 77 countries and reported through their regional transplant organizations were analyzed by main indication, donor type and stem cell source for the year 2012. With transplant rates ranging from 0.1 to 1001 per 10 million inhabitants, more HSCTs were registered from unrelated 16 433 donors than related 15 493 donors. Grafts were collected from peripheral blood (66%), bone marrow (24%; mainly non-malignant disorders) and cord blood (10%). Compared with 2006, an increase of 46% total (57% allogeneic and 38% autologous) was observed. Growth was due to an increase in reporting teams (18%) and median transplant activity/team (from 38 to 48 HSCTs/team). An increase of 167% was noted in mismatched/haploidentical family HSCT. A Strengths, Weaknesses, Opportunities, Threats (SWOT) analysis revealed the global perspective of WBMT to be its major strength and identified potential to be the key professional body for patients and authorities. The limited data collection remains its major weakness and threat. In conclusion, global HSCT grows over the years without plateauing (allogeneic>autologous) and at different rates in the four World Health Organization regions. Major increases were observed in allogeneic, haploidentical HSCT and, to a lesser extent, in cord blood transplantation. PMID- 26901705 TI - Hematopoietic stem cell transplantation for adults with EBV-positive T- or NK cell lymphoproliferative disorders: efficacy and predictive markers. PMID- 26901704 TI - Allogeneic transplantation for multiple myeloma: yes, no or maybe? PMID- 26901706 TI - Changes in the autoantibody pattern during allogeneic stem-cell transplantation for acute myeloid leukemia complicated by systemic lupus erythematosus. PMID- 26901707 TI - Efficacy of narrow band UVB in the treatment of cutaneous GvHD: an Indian experience. PMID- 26901708 TI - Greatly reduced risk of EBV reactivation in rituximab-experienced recipients of alemtuzumab-conditioned allogeneic HSCT. AB - EBV-associated post-transplant lymphoproliferative disease (PTLD) remains an important complication of allogeneic haematopoietic stem cell transplantation (allo-HSCT). We retrospectively analysed the incidence and risk factors for EBV reactivation in 186 adult patients undergoing consecutive allo-HSCT with alemtuzumab T-cell depletion at a single centre. The cumulative incidence of EBV reactivation was 48% (confidence interval (CI) 41-55%) by 1 year, with an incidence of high-level EBV reactivation of 18% (CI 13-24%); 8 patients were concurrently diagnosed with PTLD. Amongst patients with high-level reactivation 31/38 (82%) developed this within only 2 weeks of first EBV qPCR positivity. In univariate analysis age?50 years was associated with significantly increased risk of EBV reactivation (hazard ratio (HR) 1.54, CI 1.02-2.31; P=0.039). Furthermore, a diagnosis of non-Hodgkin lymphoma (NHL) was associated with greatly reduced risk of reactivation (HR 0.10, CI 0.03-0.33; P=0.0001) and this was confirmed in multivariate testing. Importantly, rituximab therapy within 6 months prior to allo-HSCT was also highly predictive for lack of EBV reactivation (HR 0.18, CI 0.07-0.48; P=0.001) although confounding with NHL was apparent. Our data emphasise the risk of PTLD associated with alemtuzumab. Furthermore, we report the clinically important observation that rituximab, administered in the peri transplant period, may provide effective prophylaxis for PTLD. PMID- 26901709 TI - Hematopoietic stem cell transplantation in Europe 2014: more than 40 000 transplants annually. AB - A record number of 40 829 hematopoietic stem cell transplantation (HSCT) in 36 469 patients (15 765 allogeneic (43%), 20 704 autologous (57%)) were reported by 656 centers in 47 countries to the 2014 survey. Trends include: continued growth in transplant activity, more so in Eastern European countries than in the west; a continued increase in the use of haploidentical family donors (by 25%) and slower growth for unrelated donor HSCT. The use of cord blood as a stem cell source has decreased again in 2014. Main indications for HSCT were leukemias: 11 853 (33%; 96% allogeneic); lymphoid neoplasias; 20 802 (57%; 11% allogeneic); solid tumors; 1458 (4%; 3% allogeneic) and non-malignant disorders; 2203 (6%; 88% allogeneic). Changes in transplant activity include more allogeneic HSCT for AML in CR1, myeloproliferative neoplasm (MPN) and aplastic anemia and decreasing use in CLL; and more autologous HSCT for plasma cell disorders and in particular for amyloidosis. In addition, data on numbers of teams doing alternative donor transplants, allogeneic after autologous HSCT, autologous cord blood transplants are presented. PMID- 26901710 TI - Physical Activity and the Risk of Gallbladder Disease: A Systematic Review and Meta-Analysis of Cohort Studies. AB - BACKGROUND: Physical activity has been hypothesized to reduce the risk of gallbladder disease (gallstones, cholecystitis, cholecystectomy); however, results from epidemiological studies have not always shown statistically significant associations. We conducted a systematic review and meta-analysis to clarify the presence and strength of an association between physical activity and gallbladder disease risk. METHODS: PubMed and Embase databases were searched for studies of physical activity and gallbladder disease up to 9th of January 2015. Prospective studies reporting relative risk (RR) estimates and 95% confidence intervals (CIs) of gallbladder disease associated with physical activity were included. Summary RRs were estimated using a random effects model. RESULTS: Eight studies including 6958 cases and 218,204 participants were included. The summary RR for the highest versus the lowest level of physical activity was 0.75 (95% CI: 0.69-0.81, n = 8) and there was no evidence of heterogeneity, I2 = 0%). In the dose-response analysis the summary relative risk per 20 MET-hours of activity was 0.85 (95% CI: 0.80-0.90, I2 = 0%, n = 2) for leisure-time physical activity, 0.83 (95% CI: 0.76-0.90, I2 = 0%, n = 2) for vigorous physical activity, and 0.86 (95% CI: 0.76-0.98, I2 = 0%, n = 2) for nonvigorous physical activity. CONCLUSION: Our analysis confirms a protective effect of physical activity on risk of gallbladder disease. PMID- 26901711 TI - Bioflocculant production by Haloplanus vescus and its application in acid brilliant scarlet yellow/red removal. AB - A novel bioflocculant MBF057 produced by a salt-tolerant Haloplanus vescus HW0579 was investigated in this study. The effects of culture conditions such as initial pH, inoculum size, and chemical oxygen demand (COD) of K-acid wastewater on MBF0579 production were studied. The result showed that 8.09 g/L purified MBF0579 was extracted with the following optimized conditions: 780 mg/L COD of K-acid wastewater as carbon source, inoculum size 12.5%, and initial pH 7.0. The biopolymer contained 78.6% polysaccharides and 21.1% proteins. The highest flocculating rate of 81.86 and 95.07% for the COD and chroma of acid brilliant scarlet gelb rot (yellow/red, GR) dye wastewater were achieved at a dosage of 150 mg/L, pH 2.0 and contact time 100 min. Overall, these findings indicate bioflocculation offers an effective alternative method of decreasing acid brilliant scarlet GR during dye wastewater treatment. PMID- 26901712 TI - Start-up of two moving bed membrane bioreactors treating saline wastewater contaminated by hydrocarbons. AB - This work aims to assess the acclimation of microorganisms to a gradual increase of salinity and hydrocarbons, during the start-up of two moving bed membrane bioreactors (MB-MBRs) fed with saline oily wastewater. In both systems an ultrafiltration membrane was used and two types of carriers were employed: polyurethane sponge cubes (MB-MBRI) and polyethylene cylindrical carriers (MB MBRII). A decreasing dilution factor of slops has been adopted in order to allow biomass acclimation. The simultaneous effect of salinity and hydrocarbons played an inhibitory role in biomass growth and this resulted in a decrease of the biological removal efficiencies. A reduction of bound extracellular polymeric substances and a simultaneous release of soluble microbial products (SMPs) were observed, particularly in the MB-MBRII system, probably due to the occurrence of a greater suspended biomass stress as response to the recalcitrance of substrate. On the one hand, a clear attachment of biomass occurred only in MB-MBRI and this affected the fouling deposition on the membrane surface. The processes of detachment and entrapment of biomass, from and into the carriers, significantly influenced the superficial cake deposition and its reversibility. On the other hand, in MB-MBRII, the higher production of SMPs implied a predominance of the pore blocking. PMID- 26901713 TI - A controlled wet-spinning and dip-coating process for preparation of high permeable TiO2 hollow fiber membranes. AB - In order to improve the permeate flux of photocatalytic membranes, we present an approach for coupling TiO2 with ceramic hollow fiber membranes. The ceramic hollow fiber membranes with high permeate flux were fabricated by a controlled wet-spinning process using polyethersulfone (PESf) and ceramic powder as precursors and 1-methyl-2-pyrrolidinone as solvent, and the subsequent TiO2 coating was performed by a dip-coating process using tetra-n-butyl titanate as precursor. It has been found that the PESf/ceramic powder ratio could influence the structure of the membranes. Here the as-prepared TiO2 hollow fiber membranes had a pure water flux of 4,450 L/(m(2).h). The performance of the TiO2 hollow fiber membrane was evaluated using humic acid (HA) as a test substance. The results demonstrated that this membrane exhibited a higher permeate flux under UV irradiation than in the dark and the HA removal efficiency was enhanced. The approach described here provides an operable route to the development of high permeable photocatalytic membranes for water treatment. PMID- 26901714 TI - Valuation of OSA process and folic acid addition as excess sludge minimization alternatives applied in the activated sludge process. AB - The aim of this study was to investigate the ability of the oxic-settling anaerobic (OSA)-process and the folic acid addition applied in the activated sludge process to reduce the excess sludge production. The study was monitored during two distinct periods: activated sludge system with OSA-process, and activated sludge system with folic acid addition. The observed sludge yields (Yobs) were 0.30 and 0.08 kgTSS kg(-1) chemical oxygen demand (COD), control phase and OSA-process (period 1); 0.33 and 0.18 kgTSS kg(-1) COD, control phase and folic acid addition (period 2). The Yobs decreased by 73 and 45% in phases with the OSA-process and folic acid addition, respectively, compared with the control phases. The sludge minimization alternatives result in a decrease in excess sludge production, without negatively affecting the performance of the effluent treatment. PMID- 26901715 TI - Dynamic control of nutrient-removal from industrial wastewater in a sequencing batch reactor, using common and low-cost online sensors. AB - On-line control of the biological treatment process is an innovative tool to cope with variable concentrations of chemical oxygen demand and nutrients in industrial wastewater. In the present study we implemented a simple dynamic control strategy for nutrient-removal in a sequencing batch reactor (SBR) treating variable tank truck cleaning wastewater. The control system was based on derived signals from two low-cost and robust sensors that are very common in activated sludge plants, i.e. oxidation reduction potential (ORP) and dissolved oxygen. The amount of wastewater fed during anoxic filling phases, and the number of filling phases in the SBR cycle, were determined by the appearance of the 'nitrate knee' in the profile of the ORP. The phase length of the subsequent aerobic phases was controlled by the oxygen uptake rate measured online in the reactor. As a result, the sludge loading rate (F/M ratio), the volume exchange rate and the SBR cycle length adapted dynamically to the activity of the activated sludge and the actual characteristics of the wastewater, without affecting the final effluent quality. PMID- 26901716 TI - Mineralization of sulfamethizole in photo-Fenton and photo-Fenton-like systems. AB - In this investigation, UV/H2O2, UV/H2O2/Fe(2+) (photo-Fenton) and UV/H2O2/Fe(3+) (photo-Fenton-like) systems were used to mineralize sulfamethizole (SFZ). The optimal doses of H2O2 (1-20 mM) in UV/H2O2 and iron (0.1-1 mM) in photo-Fenton and photo-Fenton-like systems were determined. Direct photolysis by UV irradiation and direct oxidation by added H2O2, Fe(2+) and Fe(3+) did not mineralize SFZ. The optimal dose of H2O2 was 10 mM in UV/H2O2 and that of iron (Fe(2+) or Fe(3+)) was 0.2 mM in both UV/H2O2/Fe(2+) and UV/H2O2/Fe(3+) systems. Under the best experimental conditions and after 60 min of reaction, the SFZ mineralization percentages in UV/H2O2, UV/H2O2/Fe(2+) and UV/H2O2/Fe(3+) systems were 16, 90 and 88%, respectively. The UV/H2O2/Fe(2+) and UV/H2O2/Fe(3+) systems effectively mineralized SFZ. PMID- 26901717 TI - Multivariate probability distribution for sewer system vulnerability assessment under data-limited conditions. AB - The lack of geometrical and hydraulic information about sewer networks often excludes the adoption of in-deep modeling tools to obtain prioritization strategies for funds management. The present paper describes a novel statistical procedure for defining the prioritization scheme for preventive maintenance strategies based on a small sample of failure data collected by the Sewer Office of the Municipality of Naples (IT). Novelty issues involve, among others, considering sewer parameters as continuous statistical variables and accounting for their interdependences. After a statistical analysis of maintenance interventions, the most important available factors affecting the process are selected and their mutual correlations identified. Then, after a Box-Cox transformation of the original variables, a methodology is provided for the evaluation of a vulnerability map of the sewer network by adopting a joint multivariate normal distribution with different parameter sets. The goodness-of fit is eventually tested for each distribution by means of a multivariate plotting position. The developed methodology is expected to assist municipal engineers in identifying critical sewers, prioritizing sewer inspections in order to fulfill rehabilitation requirements. PMID- 26901718 TI - Pilot scale studies on nitritation-anammox process for mainstream wastewater at low temperature. AB - Process of partial nitritation-anammox for mainstream wastewater at low temperature was run in a pilot scale moving bed biofilm reactor (MBBR) system for about 300 days. The biofilm history in the reactor was about 3 years of growth at low temperature (down to 10 degrees C). The goal of the studies presented in this paper was to achieve effective partial nitritation-anammox process. Influence of nitrogen loading rate, hydraulic retention time, aeration strategy (continuous versus intermittent) and sludge recirculation (integrated fixed-film activated sludge (IFAS) mode) on deammonification process' efficiency and microbial activity in the examined system was tested. It was found that the sole intermittent aeration strategy is not a sufficient method for successful suppression of nitrite oxidizing bacteria in MBBR. The best performance of the process was achieved in IFAS mode. The highest recorded capacity of ammonia oxidizing bacteria and anammox bacteria in biofilm was 1.4 gN/m(2)d and 0.5 gN/m(2)d, respectively, reaching 51% in nitrogen removal efficiency. PMID- 26901719 TI - Levels of six antibiotics used in China estimated by means of wastewater-based epidemiology. AB - Due to lack of proper regulation, information about antibiotics consumption in many countries such as China is difficult to obtain. In this study, a simple method based on wastewater-based epidemiology was adopted to estimate their usage in four megacities of China. Six antibiotics (norfloxacin, ofloxacin, sulfamethoxazole, trimethoprim, erythromycin and roxithromycin), which are the most frequently consumed antibiotics in China, were selected as the targets. Based on our results, Chongqing had the largest total annual consumption of the selected six antibiotics among the four megacities, followed by Guangzhou, then Hong Kong, with Beijing having the least, with values of 4.4 g/y/P, 4.0 g/y/P, 1.6 g/y/P, and 1.3 g/y/P, respectively. Compared with the daily consumption per capita in Italy, the estimated consumption levels of the selected six antibiotics in four cities of China were 12-41 times those of Italy. Our results suggested that the consumption of antibiotics in China was excessive. PMID- 26901720 TI - A novel positively charged membrane based on polyamide thin-film composite made by cross-linking for nanofiltration. AB - In this paper, a novel positively charged membrane was prepared through interfacial polymerization technique between polyethyleneimine in aqueous phase and trimesoyl chloride in organic phase. Next, cross-linking of polyamide (PA) layer using rho-xylylene dichloride (XDC) and glutaraldehyde (GA) was studied. The influences of cross-linking concentrations on the separation and permeation performance of membrane were also investigated. Membranes were characterized in terms of their chemical structure, the cross-sectional and surface morphologies, contact angles, molecular weight cut-off (MWCO) and effect of pH feed solution. The salt rejection sequence of CaCl2 >NaCl > Na2SO4 showed a positive charge at the membrane surface after cross-linking reaction. The MWCO of primary PA membrane decreased from 1,135 to 775 and 885 Da for XDC and GA, respectively. XDC membrane shows highest CaCl2 divalent cationic rejection (95.5%) and lowest water flux (21.1 L/m(2).h). This study illustrates a promising method for fabrication of positively charged membrane in cation separation. PMID- 26901721 TI - Factors affecting population of filamentous bacteria in wastewater treatment plants with nutrients removal. AB - Filamentous population in activated sludge and key operational parameters of full scale municipal wastewater treatment plants (WWTPs) with bulking problems representative for Poland were investigated with quantitative fluorescence in situ hybridization. Statistical analyses revealed few relationships between operational parameters and biovolume of filamentous bacteria. Sludge age was not only positively correlated with abundance of Chloroflexi (parametric correlation and principal component analysis (PCA)), but also differentiated Microthrix population (analysis of variance (ANOVA)). Phylum Chloroflexi and pH presented a negative relation during the study (PCA). ANOVA showed that pH of influent and sludge volume index (SVI) differentiated abundance of types 0803 and 1851 of Chloroflexi and candidate division TM7. SVI increased along with higher abundance of Microthrix (positive parametric and non-parametric correlations and positive relation in PCA). Biovolumes of morphotypes 0803 and 1851 of Chloroflexi were differentiated by organic matter in influent, also by nutrients in the case of Chloroflexi type 1851. Chemical and biological oxygen demands (COD and BOD5, respectively) were negatively correlated with Microthrix. COD also differentiated the abundance of Haliscomenobacter hydrossis. Results of the study can be used to prevent WWTPs from excessive proliferation of filamentous bacteria and operational problems caused by them--bulking and foaming of activated sludge. PMID- 26901722 TI - Dynamic modelling of nitrous oxide emissions from three Swedish sludge liquor treatment systems. AB - The objective of this paper is to model the dynamics and validate the results of nitrous oxide (N2O) emissions from three Swedish nitrifying/denitrifying, nitritation and anammox systems treating real anaerobic digester sludge liquor. The Activated Sludge Model No. 1 is extended to describe N2O production by both heterotrophic and autotrophic denitrification. In addition, mass transfer equations are implemented to characterize the dynamics of N2O in the water and the gas phases. The biochemical model is simulated and validated for two hydraulic patterns: (1) a sequencing batch reactor; and (2) a moving-bed biofilm reactor. Results show that the calibrated model is partly capable of reproducing the behaviour of N2O as well as the nitritation/nitrification/denitrification dynamics. However, the results emphasize that additional work is required before N2O emissions from sludge liquor treatment plants can be generally predicted with high certainty by simulations. Continued efforts should focus on determining the switching conditions for different N2O formation pathways and, if full-scale data are used, more detailed modelling of the measurement devices might improve the conclusions that can be drawn. PMID- 26901723 TI - Enhanced treatment of tannery wastewater in an integrated multistage bioreactor (IMBR) by the predominant bacterial strains enriched from marine sediments. AB - An innovative integrated multistage bioreactor (IMBR) system, which was augmented with three predominant bacterial strains (Lactobacillus paracasei CL1107, Pichia jadinii CL1705, and Serratia marcescens CL1502) isolated from marine sediments, was developed to treat real tannery wastewater without performing physicochemical pretreatment, with the potential to reduce the generation of waste sludge and odors. The performance of the IMBR treatment system, with and without the inclusion of the predominant bacterial strains, was compared. The results indicated that the performance of the IMBR system without bioaugmentation by the predominant bacterial strains was poor. However, when in the presence of the predominant bacterial strains, the IMBR system exhibited high removal efficiencies of chemical oxygen demand (COD) (97%), NH4(+)-N (97.7%), and total nitrogen (TN) (90%). In addition, the system had the capacity for the simultaneous removal of organics and nitrogen, heterotrophic nitrification and denitrification being carried out concurrently, thereby avoiding the strong inhibition of high concentrations of COD on nitrification. The system possessed excellent adaptability and ability to resist influent loading fluctuations, and had a good alkalinity balance such that it could achieve a high NH4(+)-N, and TN removal efficiency without a supplement of external alkalinity. In addition, an empirical performance modeling of the IMBR system was analyzed. PMID- 26901724 TI - Degradation of ethylparaben under simulated sunlight using photo-Fenton. AB - Ethylparaben (EPB) has been classified by different research groups as a potential endocrine-disrupting chemical, implying that it can potentially interfere with the normal balance of the endocrine system of living beings, which with its presence in different effluents, including drinking water, generates the need to seek methods that allow its removal from different water bodies. Advanced oxidation processes have been employed widely to remove organic compounds from different matrices. In this way, Fenton technology (process based on the reaction between ferrous ions and hydrogen peroxide) has been able to degrade different substrates, but due to the Fe(2+) requirements to carry out the reaction optimally, combination of the conventional Fenton process with visible light radiation (photo-Fenton) is an alternative used in the treatment of pollution due to the presence of chemicals. In this way, the effectiveness of photo-Fenton on EPB degradation was assessed using a face-centered central composite experimental design that allowed assessment of the effects of Fe(2+) and H2O2 initial concentrations on process. In general, results indicated that after 180 min of reaction almost all EPB was eliminated, the dissolved organic carbon in solution was reduced and the sample biodegradability index was increased. PMID- 26901725 TI - Enhancing nitrogen removal efficiency and reducing nitrate liquor recirculation ratio by improving simultaneous nitrification and denitrification in integrated fixed-film activated sludge (IFAS) process. AB - An integrated fixed-film activated sludge (IFAS) process (G1) and an activated sludge anoxic-oxic process (G2) were operated at nitrate liquor recirculation ratio (R) of 100, 200 and 300% to investigate the feasibility of enhancing nitrogen removal efficiency (RTN) and reducing R by improving simultaneous nitrification and denitrification (SND) in the IFAS process. The results showed that the effluent NH4(+)-N and total nitrogen (TN) of G1 at R of 200% were less than 1.5 and 14.5 mg/L, satisfying the Chinese discharge standard (NH4(+)-N < 5 mg/L; TN < 15 mg/L). However, the effluent NH4(+)-N and TN of G2 at R of 300% were higher than 8.5 and 15.3 mg/L. It indicated that better RTN could be achieved at a lower R in the IFAS process. The polymerase chain reaction denaturing gradient gel electrophoresis results implied that nitrifiers and denitrifiers co-existed in one microbial community, facilitating the occurrence of SND in the aerobic reactor of G1, and the contribution of SND to TN removal efficiency ranged 15-19%, which was the main reason that the RTN was improved in the IFAS process. Therefore, the IFAS process was an effective method for improving RTN and reducing R. In practical application, this advantage of the IFAS process can decrease the electricity consumption for nitrate liquor recirculation flow, thereby saving operational costs. PMID- 26901726 TI - Life cycle assessment of introducing an anaerobic digester in a municipal wastewater treatment plant in Spain. AB - Anaerobic digestion (AD) is being established as a standard technology to recover some of the energy contained in the sludge in wastewater treatment plants (WWTPs) as biogas, allowing an economy in electricity and heating and a decrease in climate gas emission. The purpose of this study was to quantify the contributions to the total environmental impact of the plant using life cycle assessment methodology. In this work, data from real operation during 2012 of a municipal WWTP were utilized as the basis to determine the impact of including AD in the process. The climate change human health was the most important impact category when AD was included in the treatment (Scenario 1), especially due to fossil carbon dioxide emissions. Without AD (Scenario 2), increased emissions of greenhouse gases, mostly derived from the use of electricity, provoked a rise in the climate change categories. Biogas utilization was able to provide 47% of the energy required in the WWTP in Scenario 1. Results obtained make Scenario 1 the better environmental choice by far, mainly due to the use of the digested sludge as fertilizer. PMID- 26901727 TI - Improved dewatering of CEPT sludge by biogenic flocculant from Acidithiobacillus ferrooxidans. AB - Bioleaching using an iron-oxidizing bacterium, Acidithiobacillus ferrooxidans, and its biogenic flocculants was evaluated to improve the dewaterability of chemically enhanced primary treatment (CEPT) sewage sludge. CEPT sludge in flasks was inoculated with A. ferrooxidans culture, medium-free cells and the cell-free culture filtrate with and without the energy substance Fe(2+), and periodically the sludge samples were analysed for the dewaterability. This investigation proves that bioleaching effectively improved the sludge dewaterability as evidenced from drastic reduction in capillary suction time (<=20 seconds) and specific resistance to filtration (>=90%); however, it requires an adaptability period of 1-2 days. On the other hand, the biogenic flocculant produced by A. ferrooxidans greatly decreased the time-to-filtration and facilitated the dewaterability within 4 h. Results indicate that rapid dewatering of CEPT sludge by biogenic flocculants provides an opportunity to replace the synthetic organic polymer for dewatering. PMID- 26901728 TI - Effect of thermal and alkaline pretreatment of giant miscanthus and Chinese fountaingrass on biogas production. AB - Giant miscanthus (Miscanthus * giganteus) and Chinese fountaingrass (Pennisetum alopecuroides (L.) Spreng), cultivated for landscaping and soil conservation, are potential energy crops. The study investigated the effect of combined thermal and alkaline pretreatments on biogas production of these energy crops. The pretreatment included two types of alkali (6% CaO and 6% NaOH) at 22, 70 and 100 degrees C. The alkaline pretreatment resulted in a greater breakdown of the hemicellulose fraction, with CaO more effective than NaOH. Pretreatment of giant miscanthus with 6% CaO at 100 degrees C for 24 h produced a CH4 yield (313 mL g( 1) volatile solids (VS)) that was 1.7 times that of the untreated sample (186 mL g(-1) VS). However, pretreatment of Chinese fountaingrass with 6% CaO or 6% NaOH at 70 degrees C for 24 h resulted in similar CH4 yields (328 and 302 mL g(-1) VS for CaO and NaOH pretreatments) as the untreated sample (311 mL g(-1) VS). Chinese fountaingrass was more easily digestible but had a low overall CH4 yield per hectare (1,831 m(3) ha(-1) y(-1)) compared to giant miscanthus (6,868 m(3) ha(-1) y(-1)). This study demonstrates the potential of thermal/alkaline pretreatment and the use of giant miscanthus and Chinese fountaingrass for biogas production. PMID- 26901729 TI - Adsorption of hexavalent chromium by crosslinked chitosan-iron(III) in an air lift reactor. AB - Column experiments were conducted in an airlift reactor containing a certain amount of crosslinked chitosan-iron(III) (Ch-Fe), to examine the effects of adsorbent mass, flow rate, and influent concentrations on Cr(VI) removal. The breakthrough time increased with an increase in Ch-Fe mass, but decreased with an increase in initial Cr(VI) concentration. The exhaustion time decreased with an increase in initial Cr(VI) concentration. The capacity at the breakthrough point increased with an increase in Ch-Fe mass, flow rate, and initial Cr(VI) concentration. The capacity at the exhaustion point increased with an increase in flow rate, but showed no specific trend with an increase in initial Cr(VI) concentration. The bed volumes at breakthrough point increased with an increase in Ch-Fe, flow rate and Cr(VI) concentration. The adsorbent exhaustion decreased with an increase in flow rate and Ch-Fe, but increased with an increase in initial Cr(VI) concentration. Columns with large amounts of Ch-Fe are preferable for obtaining optimal results during the adsorption process. The higher the flow velocity, the better the column performance. The Thomas, Clark and Yoon-Nelson models were applied to the experimental results. Good agreement was observed between the predicted theoretical breakthrough curves and the experimental results. PMID- 26901730 TI - Control of Microthrix parvicella and sludge bulking by ozone in a full-scale WWTP. AB - Bulking and rising sludge are common problems in wastewater treatment plants (WWTPs) and are primarily caused by increased growth of filamentous bacteria such as Microthrix parvicella. It has a negative impact on sludge settling properties in activated sludge (AS) process, in addition to being responsible for foam formation. Different methods can be used to control sludge bulking. The aim of this study was to evaluate the dosage of on-site generated ozone in the recycled AS flow in a full-scale WWTP having problems caused by M. parvicella. The evaluation of the experiment was assessed by process data, microscopic analysis and microbial screening on the experimental and control line before, during and after the period of ozone dosage. The ozone treatment resulted in decreased abundance of M. parvicella and improved the settling properties, without impairing the overall process performance. Both chemical oxygen demand (COD)- and N-removal were unaffected and the dominant populations involved in nitrification, as analysed by fluorescent in situ hybridization, remained during the experimental period. When the ozone treatment was terminated, the problems with sludge bulking reappeared, indicating the importance of continuous evaluation of the process. PMID- 26901731 TI - Influence of flocculation on sediment deposition process at the Three Gorges Reservoir. AB - By comparing the original particle gradation of sediment from the Three Gorges Reservoir with the single particle gradation, the differences in these two particle gradations showed that there is sediment flocculation in the Three Gorges Reservoir, which can accelerate the sediment deposition rate in the reservoir. In order to determine the influence of flocculation on the sediment settling velocity, sediment was collected at the Three Gorges Reservoir, and the indoor quiescent settling experiment was performed to study the mechanism of sediment flocculation. The experimental results showed that sediments aggregated from single particles into floccules in the settling processes. The single particles smaller than 0.022 mm will participate in the formation of floccules, which accounts for 83% of the total amount of sediment in the Three Gorges Reservoir. Moreover, the degree of sediment flocculation and the increase in sediment settling velocity were directly proportional to the sediment concentration. Taking the average particle size and the median particle size as the representative particle size, respectively, the maximum flocculation factors were calculated to be 3.4 and 5.0. Due to the sediment flocculation, the volume of sediment deposition will increase by 66% when the mass settling flux factor of total sediment had a maximum value of 1.66, suggesting that flocculation has a significant influence on the sediment deposition rate in the Three Gorges Reservoir. PMID- 26901732 TI - Adsorption and photocatalytic degradation of malachite green by vanadium doped zinc oxide nanoparticles. AB - Herein the degradation of malachite green (MG) dye from aqueous medium by vanadium doped zinc oxide (ZnO:V3%) nanopowder was investigated. The specific surface area and pore volume of the nanopowder was characterized by nitrogen adsorption method. Batch experimental procedures were conducted to investigate the adsorption and photocatalytic degradation of MG dye. Adsorption kinetics investigations were performed by varying the amount of the catalyst and the initial dye concentrations. Adsorption and photocatalytic degradation data were modeled using the Lagergren pseudo-first-order and second-order kinetic equation. The results showed that the ZnO:V3% nanopowder was particularly effective for the removal of MG and data were found to comply with Lagergreen pseudo-first-order kinetic model. PMID- 26901733 TI - Research on the stability of heavy metals (Cu, Zn) in excess sludge with the pretreatment of thermal hydrolysis. AB - Thermal hydrolysis (TH) has been used to improve anaerobic digestion performance as well as the stability of heavy metals in sludge. Because the toxicity of heavy metals is closely related to both the concentration and the chemical speciation, more exhaustive studies on speciation distribution are urgently needed. This research aimed to investigate the effects of TH treatment (especially the time and temperature) on the concentration and stability of heavy metals in sludge, and to define the optimal TH conditions. The TH experiment indicated that the content of the stable form of Cu and Zn reached 83% and 47.4%, respectively, with TH at 210 degrees C and 30 min. Compared with the raw sludge, the proportion of Cu and Zn increased by 11.88% and 7.3%, respectively. Results indicated that the heavy metals were combined with sludge in a more stable form with the pretreatment of TH, which improved the stability of heavy metals. PMID- 26901734 TI - Study of novel mechano-chemical activation process of red mud to optimize nitrate removal from water. AB - Red mud (RM) is the industrial waste of alumina production and causes serious environmental risks. In this paper, a novel activation procedure for RM (mechano chemical processing) is proposed in order to improve the nitrate adsorption from water. High-energy milling and acidification were selected as mechanical and chemical activation methods, respectively. Synthesized samples of adsorbent were produced considering two parameters of activation: acid concentrations and acidification time in two selected milling times. Optimization of the activation process was based on nitrate removal from a stock solution. Experimental data were analyzed with two-way analysis of variance and Kruskal-Wallis methods to verify and discover the accuracy and probable errors. Best conditions (acceptable removal percentage > 75) were 17.6% w/w for acid concentrate and 19.9 minutes for acidification time in 8 hours for milling time. A direct relationship between increase in nitrate removal and increasing the acid concentration and acidification time was observed. The adsorption isotherms were studied and compared with other nitrate adsorbents. Characterization tests (X-ray fluorescence, X-ray diffraction, Fourier transform infrared spectrophotometry, dynamic light scattering, surface area analysis and scanning electron microscopy) were conducted for both raw and activated adsorbents. Results showed noticeable superiority in characteristics after activation: higher specific area and porosity, lower particle size and lower agglomeration in structure. PMID- 26901735 TI - Contaminant removal in septage treatment with vertical flow constructed wetlands operated under batch flow conditions. AB - Individual septic tanks are the most common means of on-site sanitation in Malaysia, but they result in a significant volume of septage. A two-staged vertical flow constructed wetlands (VFCWs) system for the treatment of septage was constructed and studied in Sarawak, Malaysia. Raw septage was treated in the first stage wetlands, and the resulting percolate was fed onto the second stage wetlands for further treatment. Here, the effects of a batch loading regime on the contaminant removal efficiency at the second stage wetlands, which included palm kernel shell within their filter substrate, are presented. The batch loading regime with pond:rest (P:R) period of 1:1, 2:2 and 3:3 (day:day) was studied. The improvement of the effluent redox condition was evident with P:R = 3:3, resulting in excellent organic matters (chemical oxygen demand and biochemical oxygen demand) and nitrogen reduction. The bed operated with P:R = 1:1 experienced constant clogging, with a water layer observed on the bed surface. For the P:R = 3:3 regime, the dissolved oxygen profile was not found to decay drastically after 24 hours of ponding, suggesting that the biodegradation mainly occurred during the first day. The study results indicate that a suitable application regime with an adequate rest period is important in VFCWs to ensure efficient operation. PMID- 26901736 TI - Shock resistance characteristic of a spiral symmetry stream anaerobic bio reactor. AB - The shock resistance characteristic (SRC) of an anaerobic bioreactor characterizes the ability of the anaerobic community in the reactor to withstand violent change in the living environment. In comparison with an upflow anaerobic sludge blanket reactor (UASBR), the SRC of a spiral symmetry stream anaerobic bio reactor (SSSAB) was systematically investigated in terms of removal efficiency, adsorption property, settling ability, flocculability and fluctuations in these parameters. A quantitative assessment method for SRC was also developed. The results indicated that the SSSAB showed better SRC than the UASBR. The average value (m value) of chemical oxygen demand removal rates of the SSSAB was 86.0%. The contact angle of granules in the SSSAB present gradient distribution, that is the m value of contact angle increasing from bottom (84.5 degrees ) to top (93.9 degrees ). The m value of the density at the upper and lower sections of the SSSAB were 1.0611 g.cm(-3) and 1.0423 g.cm(-3), respectively. The surface mean diameter of granules in the SSSAB increased from 1.164 to 1.292 mm during operation. The absolute m value of zeta potential of granular sludge at the upper and lower sections of the SSSAB were 40.4 mV and 44.9 mV, respectively. The weighted mean coefficient variance (CV) value indicated SSSAB was more stable than the UASBR. PMID- 26901737 TI - Spatial-temporal distribution and fuzzy comprehensive evaluation of total phosphorus and total nitrogen in the Yangtze River Estuary. AB - Based on water sample data collected from the Yangtze River Estuary (YRE) during four sampling periods in 2010 and 2011, the total nitrogen (TN) and total phosphorus (TP) content were evaluated using the traditional single-factor evaluation (TSE) and the fuzzy comprehensive evaluation (FCE). Statistical analyses showed that the average TN and TP for the four periods were 2.60 mg/L and 0.11 mg/L, respectively. August 2010 showed the lowest TN (1.57 mg/L), and February 2011 showed the highest TP (0.15 mg/L). The annual spatial distribution results indicated that an area of high TN concentration (TN >= 3.0 mg/L) occurred in the adjacent sea and increased on an eastward gradient. An area of high TP concentration (TP >=0.10 mg/L) occurred in the inner YRE and decreased on an eastward gradient. There were significant differences in the results of TSE and FCE. The TSE results only reflected the TN evaluation results for certain locations of the YRE. The FCE method combined the effects of the TN and TP factors, and the results indicate that the Chinese water quality classification of Class 5 was dominant in the YRE. PMID- 26901738 TI - Evaluation of trichloroethylene degradation by starch supported Fe/Ni nanoparticles via response surface methodology. AB - In this study, degradation of trichloroethylene (TCE), a chlorinated hydrocarbon, using starch supported Fe/Ni nanoparticles was investigated. The scanning electron microscope images showed applying water soluble starch as a stabilizer for the Fe/Ni nanoparticles tended to reduce agglomeration and discrete particle. Also the mean particle diameter reduced from about 70 nm (unsupported Fe/Ni nanoparticle) to about 30 nm. Effects of three key independent operating parameters including initial TCE concentration (10.0-300.0 mg L(-1)), initial pH (4.00-10.00) and Fe(0) dosage (0.10-2.00) g L(-1) on TCE dechlorination efficiency in 1 hour were analysed by employing response surface methodology (RSM). Based on a five-level three-factor central composite design, TCE removal efficiency was examined and optimized. The obtained RSM model fitted the experimental data to a second order polynomial equation. The optimum dechlorination conditions at initial TCE concentration 100.0 mg L(-1) were initial pH 5.77, Fe(0) dosage 1.67 g L(-1). At these conditions TCE removal concentration reached 94.87%, which is in close acceptance with predicted value by the RSM model. PMID- 26901739 TI - Effect of cathode electron acceptors on simultaneous anaerobic sulfide and nitrate removal in microbial fuel cell. AB - The current investigation reports the effect of cathode electron acceptors on simultaneous sulfide and nitrate removal in two-chamber microbial fuel cells (MFCs). Potassium permanganate and potassium ferricyanide were common cathode electron acceptors and evaluated for substrate removal and electricity generation. The abiotic MFCs produced electricity through spontaneous electrochemical oxidation of sulfide. In comparison with abiotic MFC, the biotic MFC showed better ability for simultaneous nitrate and sulfide removal along with electricity generation. Keeping external resistance of 1,000 Omega, both MFCs showed good capacities for substrate removal where nitrogen and sulfate were the main end products. The steady voltage with potassium permanganate electrodes was nearly twice that of with potassium ferricyanide. Cyclic voltammetry curves confirmed that the potassium permanganate had higher catalytic activity than potassium ferricyanide. The potassium permanganate may be a suitable choice as cathode electron acceptor for enhanced electricity generation during simultaneous treatment of sulfide and nitrate in MFCs. PMID- 26901740 TI - Removal of 4-nitrophenol from aqueous solution by adsorption onto activated carbon prepared from Acacia glauca sawdust. AB - The present paper deals with a complete batch adsorption study of 4-nitrophenol (4NP) from aqueous solution onto activated carbon prepared from Acacia glauca sawdust (AGAC). The surface area of the adsorbent determined by methylene blue method is found to be 311.20 m(2)/g. The optimum dose of adsorbent was found to be 2 g/l with 4NP uptake of 25.93 mg/g. The equilibrium time was found to be 30 minutes with the percentage removal of 96.40 at the initial concentration of 50 ppm. The maximum removal of 98.94% was found to be at pH of 6. The equilibrium and kinetic study revealed that the Radke-Prausnitz isotherm and pseudo second order kinetics model fitted the respective data well. In the thermodynamic study, the negative value of Gibbs free energy change (-26.38 kJ/mol at 30 degrees C) and enthalpy change (-6.12 kJ/mol) showed the spontaneous and exothermic nature of the adsorption process. PMID- 26901741 TI - Erratum: Water Science and Technology 72 (11), 2034-2044: A downflow hanging sponge (DHS) reactor for faecal coliform removal from an upflow anaerobic sludge blanket (UASB) effluent, Rosa Elena Yaya Beas, Katarzyna Kujawa-Roeleveld, Jules B. van Lier and Grietje Zeeman, doi: 10.2166/wst.2015.427. PMID- 26901743 TI - Dioxins, furans, biphenyls, arsenic, thorium and uranium in natural and anthropogenic sources of phosphorus and calcium used in agriculture. AB - The aim of this study was to assess the presence of dioxins, furans and biphenyls, and the inorganic contaminants such as arsenic (As), thorium (Th) and uranium (U) in three main products used in Agriculture in Brazil: feed grade dicalcium phosphate, calcined bovine bone meal and calcitic limestone. The first two are anthropogenic sources of phosphorus and calcium, while calcitic limestone is a natural unprocessed mineral. Regarding to dioxin-like substances, all samples analyzed exhibited dioxins (PCDD) and furans (PCDF) and dioxin-like polychlorinated biphenyls (dl-PCBs) concentrations below limit of detection (LOD). In general, achieved is in accordance with regulation in Brazil where is established a maximum limit in limestone used in the citric pulp production (0.50pg WHO-TEQ g(-1)). In addition, reported data revealed very low levels for limestone in comparison with similar materials reported by European legislation. As result for toxic metals, achieved data were obtained using Instrumental Neutron Activation Analysis (INAA). On one hand, limestone sample exhibits the largest arsenic concentration. On another hand, dicalcium phosphate exhibited the largest uranium concentration, which represents a standard in animal nutrition. Therefore, it is phosphorus source in the animal feed industry can be a goal of concern in the feed field. PMID- 26901744 TI - The association of weather on pediatric emergency department visits in Changwon, Korea (2005-2014). AB - BACKGROUND: It is widely believed that patients are less likely to visit hospitals during bad weather. We hypothesized that weather and emergency department (ED) visits are associated. Thus, we investigated the association between pediatric ED visits and weather, and sought to determine whether admissions to the ED are affected by meteorological factors. METHODS: We retrospectively analyzed all 87,242 emergency visits to Samsung Changwon Hospital by pediatric patients under 19years of age from January 2005 to December 2014. ED visits were categorized by disease. We used Poisson regression and generalized linear model to examine the relationships between current weather and ED visits. Additionally a distributed lag non-linear model was used to investigate the effect of weather on ED visits. RESULTS: During this 10-year study period, the average temperature and diurnal temperature range (DTR) were 14.7 degrees C and 8.2 degrees C, respectively. There were 1,145days of rain or snow (31.4%) during the 3,652-day study period. The volume of ED visits decreased on days of rain or snow. Additionally ED visits increased 2days after rainy or snowy days. The volume of ED visits increased 1.013 times with every 1 degrees C increase in DTR. The volume of ED visits by patients with trauma, digestive diseases, and respiratory diseases increased when DTR was over 10 degrees C. As rainfall increased to over 25mm, the ward admission rate (23.8%, p=0.018) of ED patients increased significantly. CONCLUSION: The volume of ED visits decreased on days of rain or snow and the ED visits were increased 2days after rainy or snowy days. The volume of ED visits increased for every 1 degrees C increase in DTR. PMID- 26901745 TI - Single house on-site grey water treatment using a submerged membrane bioreactor for toilet flushing. AB - Wastewater recycling has been and continues to be practiced all over the world for a variety of reasons including: increasing water availability, combating water shortages and drought, and supporting environmental and public health protection. Nowadays, one of the most interesting issues for wastewater recycling is the on-site treatment and reuse of grey water. During this study the efficiency of a compact Submerged Membrane Bioreactor (SMBR) system to treat real grey water in a single house in Crete, Greece, was examined. In the study, grey water was collected from a bathtub, shower and washing machine containing significant amounts of organic matter and pathogens. Chemical oxygen demand (COD) removal in the system was approximately 87%. Total suspended solids (TSS) were reduced from 95mgL(-1) in the influent to 8mgL(-1) in the effluent. The efficiency of the system to reduce anionic surfactants was about 80%. Fecal and total coliforms decreased significantly using the SMBR system due to rejection, by the membrane, used in the study. Overall, the SMBR treatment produces average effluent values that would satisfy international guidelines for indoor reuse applications such as toilet flushing. PMID- 26901746 TI - Is goal ascription possible in minimal mindreading? AB - In this response to the commentary by Michael and Christensen, we first explain how minimal mindreading is compatible with the development of increasingly sophisticated mindreading behaviors that involve both executive functions and general knowledge and then sketch 1 approach to a minimal account of goal ascription. PMID- 26901747 TI - Thermal Emissivity-Based Chemical Spectroscopy through Evanescent Tunneling. AB - A new spectroscopic technique is presented, with which environmentalchemistry induced thermal emissivity changes of thin films are extracted with high isolation through evanescent tunneling. With this method the hydrogen-induced emissivity changes of films of TiO2 , Pd-TiO2 , and Au-TiO2 , with properties of high conductivity, hydrogen chemisorption, and plasmonic activity, are characterized in the UV-vis and NIR wavelength ranges, at 1073 K. PMID- 26901748 TI - A New 35-mm Short Intra-aortic Balloon Catheter: A Suitable Option Also for Non Small-Sized Patients? AB - OBJECTIVE: Visceral ischemia can be a potentially life-threatening complication of intra-aortic balloon pump (IABP) support. A shorter IABP catheter might lead to a reduction of visceral complications. In this animal study, we evaluate the effects of a 35-mL short catheter in comparison with a 40-mL standard-sized catheter. METHODS: Eighteen healthy swine underwent 120-minute ligation of the left anterior descending coronary artery followed by 6 hours of reperfusion being supported by either a short IABP catheter (short group) (n = 6) or a long IABP catheter (long group) (n = 6) or with no assistance (controls) (n = 6). Hemodynamics, visceral and coronary flows, as well as biochemical markers were evaluated throughout the different phases of the protocol. RESULTS: Mesenteric flows increased significantly at reperfusion (P < 0.001 both) remaining constant afterward (all, P > 0.05) in the short group, while remaining significantly lower in the long group at the start of reperfusion, remaining constantly lower than the short group and controls (P < 0.001 vs short, P < 0.003 vs controls). In both long and short groups, catheters improved renal flows at reperfusion (P < 0.001 both) without any further variation (P > 0.05). In the short group, the flows were higher during the whole of reperfusion (all, P < 0.05). Intra-aortic balloon pump support improved hemodynamic indices and coronary blood flows during reperfusion to a similar extent in both the small and the long group (P > 0.05). CONCLUSIONS: The short IABP catheter proved to be as effective as the standard sized catheter in supporting hemodynamics and coronary circulation. Furthermore, it even improves visceral flows in comparison with conventional IABP catheters. PMID- 26901749 TI - Nicorandil Infusion During Off-Pump Coronary Artery Bypass Grafting Reduces Incidence of Intra-aortic Balloon Pump Insertion. AB - OBJECTIVE: Off-pump coronary artery bypass grafting in patients with left ventricular dysfunction has proven to be advantageous. However, it carries risk of emergency conversion to cardiopulmonary bypass. We have successfully used an intra-aortic balloon pump to prevent such conversion. The objective of the present study was to evaluate if intravenous nicorandil infusion reduces the incidence of intraoperative intra-aortic balloon pump insertion. METHODS: Consecutive cases of isolated off-pump coronary artery bypass surgery performed by a single surgeon were studied. Patients were divided into two groups. The first group did not receive nicorandil, and the second group received intraoperative nicorandil infusion (started in the operating room after central line insertion). RESULTS: A total of 375 patients were included in the study. Four patients in the non-nicorandil group and the patients in nicorandil group were on preoperative intra-aortic balloon pump and hence excluded from the study. After routine use of nicorandil infusion, incidence of intra-aortic balloon pump insertion during off-pump coronary artery bypass surgery decreased from 12.4% (21/169) to 2.9% (6/206). CONCLUSIONS: Nicorandil infusion significantly (P = 0.007) reduced the incidence of intra-aortic balloon pump insertion in our series. In patients with left ventricular dysfunction (ejection fraction <= 30%), this difference (P = 0.008) assumes a special significance as off-pump bypass surgery is considered high risk in this subset. Nicorandil is an inexpensive drug, and the reduction in cost of surgery by avoiding intra-aortic balloon pump insertion is an added advantage. The use of nicorandil infusion during off-pump coronary artery bypass may result in favorable patient outcomes by reducing invasive intra-aortic balloon pump insertion during off-pump coronary artery bypass grafting. PMID- 26901750 TI - External Saphenous Vein Support Mesh Does Not Interfere With Transit-Time Flow Measurement on Venous Coronary Bypass Conduit: Clinical Confirmation. AB - A 65-year-old patient underwent double coronary artery bypass grafting using the left internal thoracic artery on the left anterior descending coronary artery and nitinol alloy mesh [external Saphenous Vein Support (eSVS)]-covered saphenous vein graft to the right posterior descending coronary artery. Transit-time flow measurements (TTFMs) were obtained on meshed and bare parts of the vein graft. There was no difference in TTFM parameters (flow, pulsatility index, and diastolic fraction values) obtained from the eSVS mesh-covered and the uncovered parts of the venous graft. This observation confirms that eSVS mesh does not interfere with TTFM on venous coronary bypass conduits. PMID- 26901751 TI - An Ixodes ricinus Tick Salivary Lectin Pathway Inhibitor Protects Borrelia burgdorferi sensu lato from Human Complement. AB - INTRODUCTION: We previously identified tick salivary lectin pathway inhibitor (TSLPI) in Ixodes scapularis, a vector for Borrelia burgdorferi sensu stricto (s.s.) in North America. TSLPI is a salivary protein facilitating B. burgdorferi s.s. transmission and acquisition by inhibiting the host lectin complement pathway through interference with mannose binding lectin (MBL) activity. Since Ixodes ricinus is the predominant vector for Lyme borreliosis in Europe and transmits several complement sensitive B. burgdorferi sensu lato (s.l.) strains, we aimed to identify, describe, and characterize the I. ricinus ortholog of TSLPI. METHODS: We performed (q)PCRs on I. ricinus salivary gland cDNA to identify a TSLPI ortholog. Next, we generated recombinant (r)TSLPI in a Drosophila expression system and examined inhibition of the MBL complement pathway and complement-mediated killing of B. burgdorferi s.l. in vitro. RESULTS: We identified a TSLPI ortholog in I. ricinus salivary glands with 93% homology at the RNA and 89% at the protein level compared to I. scapularis TSLPI, which was upregulated during tick feeding. In silico analysis revealed that TSLPI appears to be part of a larger family of Ixodes salivary proteins among which I. persulcatus basic tail salivary proteins and I. scapularis TSLPI and Salp14. I. ricinus rTSLPI inhibited the MBL complement pathway and protected B. burgdorferi s.s. and Borrelia garinii from complement-mediated killing. CONCLUSION: We have identified a TSLPI ortholog, which protects B. burgdorferi s.l. from complement mediated killing in I. ricinus, the major vector for tick-borne diseases in Europe. PMID- 26901752 TI - Genetic polymorphisms of pharmacogenomic VIP variants in Li nationality of southern China. AB - OBJECTIVES: The present study aimed to screen members of the Li nationality in southern China for genotype frequencies of VIP variants and to determine differences between the Li ethnicity and global human population samples in HapMap. METHODS: In this study, we genotyped 77 very important pharmacogenetic (VIP) variants selected from the pharmacogenomics knowledge base (PharmGKB) in members of the Li population and compared our data with other eleven populations from the HapMap data set. RESULTS: Our results showed that VDR rs1540339, VKORC1 rs9934438, and MTHFR rs1801133 were most different in Li compared with most of the eleven populations from the HapMap data set. Furthermore, population structure and F-statistics (Fst) analysis also showed differences between the Li and other HapMap populations, and the results suggest that the Li are most genetically similar to the CHD population, and the least similar to the YRI in HapMap. CONCLUSIONS: The findings of our study complement the pharmacogenomics database with information on members of the Li ethnicity and provide a stronger scientific basis for safer drug administration, which may help clinicians to predict individual drug responses, thereby avoiding the risk of adverse effects and optimizing efficacy in this population. PMID- 26901756 TI - Hyaluronic acid modified mesoporous carbon nanoparticles for targeted drug delivery to CD44-overexpressing cancer cells. AB - In this paper, hyaluronic acid (HA) functionalized uniform mesoporous carbon spheres (UMCS) were synthesized for targeted enzyme responsive drug delivery using a facile electrostatic attraction strategy. This HA modification ensured stable drug encapsulation in mesoporous carbon nanoparticles in an extracellular environment while increasing colloidal stability, biocompatibility, cell targeting ability, and controlled cargo release. The cellular uptake experiments of fluorescently labeled mesoporous carbon nanoparticles, with or without HA functionalization, demonstrated that HA-UMCS are able to specifically target cancer cells overexpressing CD44 receptors. Moreover, the cargo loaded doxorubicin (DOX) and verapamil (VER) exhibited a dual pH and hyaluronidase-1 responsive release in the tumor microenvironment. In addition, VER/DOX/HA-UMCS exhibited a superior therapeutic effect on an in vivo HCT-116 tumor in BALB/c nude mice. In summary, it is expected that HA-UMCS will offer a new method for targeted co-delivery of drugs to tumors overexpressing CD44 receptors. PMID- 26901757 TI - Before theory comes theorizing or how to make social science more interesting. AB - The basic argument in this article is that sociology and social science more generally are today severely hampered by the lack of attention being paid to theory. Methods--qualitative as well as quantitative methods--have proven to be very useful in practical research (as opposed to theory); and as a result they dominate modern social science. They do not, however, do the job that belongs to theory. One way to redress the current imbalance between methods and theory, it is suggested, would be to pay more attention to theorizing, that is, to the actual process that precedes the final formulation of a theory; and in this way improve theory. Students of social science are today primarily exposed to finished theories and are not aware of the process that goes into the production and design of a theory. Students need to be taught how to construct a theory in practical terms ('theorizing'); and one good way to do so is through exercises. This is the way that methods are being taught by tradition; and it helps the students to get a hands-on knowledge, as opposed to just a reading knowledge of what a theory is all about. Students more generally need to learn how to construct a theory while drawing on empirical material. The article contains a suggestion for the steps that need to be taken when you theorize. Being trained in what sociology and social science are all about--an important precondition!- students may proceed as follows. You start out by observing, in an attempt to get a good empirical grip on the topic before any theory is introduced. Once this has been done, it may be time to name the phenomenon; and either turn the name into a concept as the next step or bring in some existing concepts in an attempt to get a handle on the topic. At this stage one can also try to make use of analogies, metaphors and perhaps a typology, in an attempt to both give body to the theory and to invest it with some process. The last element in theorizing is to come up with an explanation; and at this point it may be helpful to draw on some ideas by Charles Peirce, especially his notion of abduction. Before having been properly tested against empirical material, according to the rules of the scientific community, the theory should be considered unproven. Students who are interested in learning more about theorizing may want to consult the works of such people as Everett C. Hughes, C. Wright Mills, Ludwig Wittgenstein and James G. March. Many of the issues that are central to theorizing are today also being studied in cognitive science; and for those who are interested in pursuing this type of literature, handbooks represent a good starting point. The article ends by arguing that more theorizing will not only redress the balance between theory and methods; it will also make sociology and social science more interesting. PMID- 26901758 TI - Epidemiologic Research on Malformations Associated with Cleft Lip and Cleft Palate in Japan. AB - To investigate malformations associated with cleft lip and cleft palate, we conducted surveys at neonatal intensive care units (NICUs) and other non-NICU facilities and to determine whether there are differences among facilities. The regional survey investigated NICU facilities located in Oita Prefecture, including 92 patients with cleft lip and palate (CLP) or cleft palate (CP) that occurred between 2004 and 2013, and the national survey investigated oral surgery, plastic surgery, and obstetrics and gynecology facilities located in Japan, including 16,452 patients with cleft lip (CL), CLP, or CP that occurred since 2000. The incidence per 10,000 births was 4.2, 6.2, and 2.8 for CL, CLP, and CP, respectively, according to the national survey, and 6.3 and 2.9 for CLP and CP, respectively according to the regional survey. These results indicated comparable incidences between the two surveys. In contrast, when the survey results on malformations associated with CLP and CP according to the ICD-10 classification were compared between the national survey conducted at oral surgery or plastic surgery facilities and the regional survey conducted at NICU facilities, the occurrence of associated malformations was 19.8% vs. 41.3% for any types of associated malformation, 6.8% vs. 21.7% for congenital heart disease, and 0.5% vs. 16.3% for chromosomal abnormalities. These results indicated that the incidences of all of these associated malformations were significantly greater in the survey conducted at NICU facilities and similar to the findings from international epidemiological surveys. When comparing the survey conducted at obstetrics facilities vs. NICU facilities, the occurrence of associated malformations was similar results as above. The incidence of CLP and CP was not different between surveys conducted at NICU facilities vs. non-NICU facilities; however, when conducting surveys on associated malformations, it is possible to obtain accurate epidemiological data by investigating NICU facilities where detailed examinations are thoroughly performed. PMID- 26901759 TI - Tel1 and Rif2 Regulate MRX Functions in End-Tethering and Repair of DNA Double Strand Breaks. AB - The cellular response to DNA double-strand breaks (DSBs) is initiated by the MRX/MRN complex (Mre11-Rad50-Xrs2 in yeast; Mre11-Rad50-Nbs1 in mammals), which recruits the checkpoint kinase Tel1/ATM to DSBs. In Saccharomyces cerevisiae, the role of Tel1 at DSBs remains enigmatic, as tel1Delta cells do not show obvious hypersensitivity to DSB-inducing agents. By performing a synthetic phenotype screen, we isolated a rad50-V1269M allele that sensitizes tel1Delta cells to genotoxic agents. The MRV1269MX complex associates poorly to DNA ends, and its retention at DSBs is further reduced by the lack of Tel1. As a consequence, tel1Delta rad50-V1269M cells are severely defective both in keeping the DSB ends tethered to each other and in repairing a DSB by either homologous recombination (HR) or nonhomologous end joining (NHEJ). These data indicate that Tel1 promotes MRX retention to DSBs and this function is important to allow proper MRX-DNA binding that is needed for end-tethering and DSB repair. The role of Tel1 in promoting MRX accumulation to DSBs is counteracted by Rif2, which is recruited to DSBs. We also found that Rif2 enhances ATP hydrolysis by MRX and attenuates MRX function in end-tethering, suggesting that Rif2 can regulate MRX activity at DSBs by modulating ATP-dependent conformational changes of Rad50. PMID- 26901760 TI - Prawn Shell Chitosan Exhibits Anti-Obesogenic Potential through Alterations to Appetite, Affecting Feeding Behaviour and Satiety Signals In Vivo. AB - The crustacean shells-derived polysaccharide chitosan has received much attention for its anti-obesity potential. Dietary supplementation of chitosan has been linked with reductions in feed intake, suggesting a potential link between chitosan and appetite control. Hence the objective of this experiment was to investigate the appetite suppressing potential of prawn shell derived chitosan in a pig model. Pigs (70 +/- 0.90 kg, 125 days of age, SD 2.0) were fed either T1) basal diet or T2) basal diet plus 1000 ppm chitosan (n = 20 gilts per group) for 63 days. The parameter categories which were assessed included performance, feeding behaviour, serum leptin concentrations and expression of genes influencing feeding behaviour in the small intestine, hypothalamus and adipose tissue. Pigs offered chitosan visited the feeder less times per day (P<0.001), had lower intake per visit (P<0.001), spent less time eating per day (P<0.001), had a lower eating rate (P<0.01) and had reduced feed intake and final body weight (P< 0.001) compared to animals offered the basal diet. There was a treatment (P<0.05) and time effect (P<0.05) on serum leptin concentrations in animals offered the chitosan diet compared to animals offered the basal diet. Pigs receiving dietary chitosan had an up-regulation in gene expression of growth hormone receptor (P<0.05), Peroxisome proliferator activated receptor gamma (P<0.01), neuromedin B (P<0.05), neuropeptide Y receptor 5 (P<0.05) in hypothalamic nuclei and neuropeptide Y (P<0.05) in the jejunum. Animals consuming chitosan had increased leptin expression in adipose tissue compared to pigs offered the basal diet (P<0.05). In conclusion, these data support the hypothesis that dietary prawn shell chitosan exhibits anti-obesogenic potential through alterations to appetite, and feeding behaviour affecting satiety signals in vivo. PMID- 26901761 TI - Evidence for Host-Genotype Associations of Borrelia burgdorferi Sensu Stricto. AB - Different genotypes of the agent of Lyme disease in North America, Borrelia burgdorferi sensu stricto, show varying degrees of pathogenicity in humans. This variation in pathogenicity correlates with phylogeny and we have hypothesized that the different phylogenetic lineages in North America reflect adaptation to different host species. In this study, evidence for host species associations of B. burgdorferi genotypes was investigated using 41 B. burgdorferi-positive samples from five mammal species and 50 samples from host-seeking ticks collected during the course of field studies in four regions of Canada: Manitoba, northwestern Ontario, Quebec, and the Maritimes. The B. burgdorferi genotypes in the samples were characterized using three established molecular markers (multi locus sequence typing [MLST], 16S-23S rrs-rrlA intergenic spacer, and outer surface protein C sequence [ospC] major groups). Correspondence analysis and generalized linear mixed effect models revealed significant associations between B. burgdorferi genotypes and host species (in particular chipmunks, and white footed mice and deer mice), supporting the hypotheses that host adaptation contributes to the phylogenetic structure and possibly the observed variation in pathogenicity in humans. PMID- 26901762 TI - Risk Factors and Post-Resection Independent Predictive Score for the Recurrence of Hepatitis B-Related Hepatocellular Carcinoma. AB - BACKGROUND: Independent risk factors associated with hepatitis B (HBV)-related hepatocellular carcinoma (HCC) after resection remains unknown. An accurate risk score for HCC recurrence is lacking. METHODS: We prospectively followed up 200 patients who underwent liver resection for HBV-related HCC for at least 2 years. Demographic, biochemical, tumor, virological and anti-viral treatment factors were analyzed to identify independent risk factors associated with recurrence after resection and a risk score for HCC recurrence formulated. RESULTS: Two hundred patients (80% male) who underwent liver resection for HBV-related HCC were recruited. The median time of recurrence was 184 weeks (IQR 52-207 weeks) for the entire cohort and 100 patients (50%) developed HCC recurrence. Stepwise Cox regression analysis identified that one-month post resection HBV DNA >20,000 IU/mL (p = 0.019; relative risk (RR) 1.67; 95% confidence interval (C.I.): 1.09 2.57), the presence of lymphovascular permeation (p<0.001; RR 2.69; 95% C.I.: 1.75-4.12), microsatellite lesions (p<0.001; RR 2.86; 95% C.I.: 1.82-4.51), and AFP >100ng/mL before resection (p = 0.021; RR 1.63; 95% C.I.: 1.08-2.47) were independently associated with HCC recurrence. Antiviral treatment before resection (p = 0.024; RR 0.1; 95% C.I.: 0.01-0.74) was independently associated with reduced risk of HCC recurrence. A post-resection independent predictive score (PRIPS) was derived and validated with sensitivity of 75.3% and 60.6% and specificity of 55.7% and 79.2%, to predict the 1- and 3-year risks for the HCC recurrence respectively with the hazard ratio of 2.71 (95% C.I.: 2.12-3.48; p<0.001). The AUC for the 1- and 3-year prediction were 0.675 (95% C.I.: 0.6 0.78) and 0.746 (95% C.I.: 0.69-0.82) respectively. CONCLUSION: Several tumor, virological and biochemical factors were associated with a higher cumulative risk of HCC recurrence after resection. PRIPS was derived for more accurate risk assessment. Regardless of the HBV DNA level, antiviral treatment should be given to patients before resection to reduce the risk of recurrence. PMID- 26901763 TI - Modeling Soil Carbon Dynamics in Northern Forests: Effects of Spatial and Temporal Aggregation of Climatic Input Data. AB - Boreal forests contain 30% of the global forest carbon with the majority residing in soils. While challenging to quantify, soil carbon changes comprise a significant, and potentially increasing, part of the terrestrial carbon cycle. Thus, their estimation is important when designing forest-based climate change mitigation strategies and soil carbon change estimates are required for the reporting of greenhouse gas emissions. Organic matter decomposition varies with climate in complex nonlinear ways, rendering data aggregation nontrivial. Here, we explored the effects of temporal and spatial aggregation of climatic and litter input data on regional estimates of soil organic carbon stocks and changes for upland forests. We used the soil carbon and decomposition model Yasso07 with input from the Norwegian National Forest Inventory (11275 plots, 1960-2012). Estimates were produced at three spatial and three temporal scales. Results showed that a national level average soil carbon stock estimate varied by 10% depending on the applied spatial and temporal scale of aggregation. Higher stocks were found when applying plot-level input compared to country-level input and when long-term climate was used as compared to annual or 5-year mean values. A national level estimate for soil carbon change was similar across spatial scales, but was considerably (60-70%) lower when applying annual or 5-year mean climate compared to long-term mean climate reflecting the recent climatic changes in Norway. This was particularly evident for the forest-dominated districts in the southeastern and central parts of Norway and in the far north. We concluded that the sensitivity of model estimates to spatial aggregation will depend on the region of interest. Further, that using long-term climate averages during periods with strong climatic trends results in large differences in soil carbon estimates. The largest differences in this study were observed in central and northern regions with strongly increasing temperatures. PMID- 26901765 TI - The Majority of the Pre-Antiretroviral Population Who Were Lost to Follow-Up Stopped Their Care in Freetown, Sierra Leone: A 12-Month Prospective Cohort Study Starting with HIV Diagnosis. AB - BACKGROUND: The heterogeneity of the pre-antiretroviral (pre-ART) population calls for more granular depictions of the cascade of HIV care. METHODS: We studied a prospective cohort of persons newly diagnosed with HIV infection from a single center in Freetown, Sierra Leone, over a 12-month period and then traced those persons who were lost to follow-up (LTFU) during pre-ART care (before ART initiation). ART eligibility was based on a CD4 cell count result of <= 350 mm/cells and/or WHO clinical stage 3 or 4. Persons who attended an appointment in the final three months were considered to be retained in care. Adherence to ART was measured using pharmacy refill dates. "Effective HIV care" was defined as completion of the cascade of care at 12-months regardless of whether patients are on ART. Tracing outcomes were obtained for those who were LTFU during pre-ART care. RESULTS: 408 persons newly diagnosed with HIV infection were screened, 338 were enrolled, and 255 persons were staged for ART. ART-ineligible persons had higher retention rates than ART-eligible persons (59.6% vs 41.8%, p = 0.03). 77 (22.8%) of 338 persons received effective HIV care. Most attrition (61.9%) occurred with persons during pre-ART care. 123 of 138 persons (89.1%) who were LTFU prior to ART initiation were found, and 91 of those 123 (74.0%) were alive. Of the 74 persons who were alive and described their engagement in care, 40 (54.1%) stopped care. Nearly half (42.5%) of those 40 stopped after assessment of ART-eligibility but before ART initiation. The main limitation of this study was the lack of tracing outcomes for those lost during ART care. CONCLUSIONS: The majority of the pre-ART LTFU population stopped their care, particularly after ART-eligibility but before ART initiation. Interventions to hasten ART initiation and retain this at-risk group may have significant downstream impact on effective HIV care. PMID- 26901764 TI - Trisulfate Disaccharide Decreases Calcium Overload and Protects Liver Injury Secondary to Liver Ischemia/Reperfusion. AB - BACKGROUND: Ischemia and reperfusion (I/R) causes tissue damage and intracellular calcium levels are a factor of cell death. Sodium calcium exchanger (NCX) regulates calcium extrusion and Trisulfated Disaccharide (TD) acts on NCX decreasing intracellular calcium through the inhibition of the exchange inhibitory peptide (XIP). OBJECTIVES: The aims of this research are to evaluate TD effects in liver injury secondary to I/R in animals and in vitro action on cytosolic calcium of hepatocytes cultures under calcium overload. METHODS: Wistar rats submitted to partial liver ischemia were divided in groups: CONTROL: (n = 10): surgical manipulation with no liver ischemia; Saline: (n = 15): rats receiving IV saline before reperfusion; and TD: (n = 15): rats receiving IV TD before reperfusion. Four hours after reperfusion, serum levels of AST, ALT, TNF alpha, IL-6, and IL-10 were measured. Liver tissue samples were collected for mitochondrial function and malondialdehyde (MDA) content. Pulmonary vascular permeability and histologic parameters of liver were determined. TD effect on cytosolic calcium was evaluated in BRL3A hepatic rat cell cultures stimulated by thapsigargin pre and after treatment with TD. RESULTS: AST, ALT, cytokines, liver MDA, mitochondrial dysfunction and hepatic histologic injury scores were less in TD group when compared to Saline Group (p<0.05) with no differences in pulmonary vascular permeability. In culture cells, TD diminished the intracellular calcium raise and prevented the calcium increase pre and after treatment with thapsigargin, respectively. CONCLUSION: TD decreases liver cell damage, preserves mitochondrial function and increases hepatic tolerance to I/R injury by calcium extrusion in Ca2+ overload situations. PMID- 26901766 TI - Bigger Is Not Always Better: Females Prefer Males of Mean Body Size in Philautus odontotarsus. AB - Most species are believed to evolve larger body sizes over evolutionary time. Previous studies have suggested that sexual selection, through male-male competition and female choice, favors larger males. However, there is little evidence of selection against large size. The female serrate-legged small treefrogs (Philautus odontotarsus) must carry passive males from leks to breeding grounds over relatively long distances after amplexus to find a suitable place to lay eggs. The costs of large male size may therefore decrease mating success due to reduced agility and/or higher energy requirements. Thus, we hypothesized that selection would not favor larger males in P. odontotarsus. Females can assess male body size on the basis of the dominant frequency of male calls in frogs. To assess female P. odontotarsus preferences for a potential mate's body size, male calls of high, average and low dominant frequency were played back to the females in phonotaxis experiments. Results showed that most females prefer the advertisement call with average dominant frequency. In addition, we compared the body mass distribution of amplectant males with that of single males in nature. The body masses of amplectant males are more narrowly distributed in the intermediate range than that of single males. The phonotaxis results and the data of actual female preferences in the field show that females strongly prefer potential mates of mean body sizes, consistent with the view that, in this species at least, larger males are not always perceived as better by females. In the present study, P. odontotarsus provides an example of an amphibian species in which large size does not have an advantage in mating success for males. Instead, our results provide evidences that stabilizing selection favors the optimal intermediate size of males. PMID- 26901767 TI - Proximal and Distal Predictors of the Spider Monkey's Stress Levels in Fragmented Landscapes. AB - The rapid loss, fragmentation and degradation of tropical forests threaten the survival of many animal species. However, the way in which these phenomena affect animal health has been poorly explored, thus limiting the design of appropriate conservation strategies. To address this, here we identified using linear mixed models the effect of proximal (diet, activity pattern, hunting and logging) and distal (sum of the basal areas of fruiting-tree species [SBAFS], landscape forest cover and degree of forest fragmentation) variables over fecal glucocorticoid metabolite (fGCM) levels-hormones associated with animal health and fitness-of six groups of spider monkeys (Ateles geoffroyi) inhabiting six landscapes with different spatial structures in Mexico. Proximal variables showed a stronger predictive power over fGCMs than distal. In this sense, increases in travel time, the occurrence of hunting, and reductions in rest time and fruit consumption resulted in higher fGCM levels. Regarding distal variables, increases in SBAFS were negatively related to fGCM levels, thus suggesting that food scarcity increases stress hormone levels. Nevertheless, contrary to theoretical expectations, spider monkeys living in smaller tracts of forest spent less time travelling, but the same time feeding on fruit as those in more forested areas. The lower net energy return associated with this combination of factors would explain why, contrary to theoretical expectations, increased forest cover was associated with increased levels of fGCMs in these groups. Our study shows that, at least in the short term, spider monkeys in fragmented landscapes do not always present higher levels of stress hormones compared to those inhabiting continuous forest, and the importance of preserving fruit sources and controlling hunting for reducing the levels of stress hormones in free ranging spider monkeys. PMID- 26901768 TI - Congenital neuroblastoma with symptoms of epidural compression at birth. AB - The occurrence of congenital neuroblastoma presenting at birth with symptoms of epidural compression secondary to spinal canal invasion is rare. Almost all cases reported in the literature have survived from the tumor but suffer severe sequelae, with the exception of the 2 most recently described whose birth was anticipated. The 3 cases of this article have been followed for a minimum of 5 years with the aim to describe their definitive late complications. In none of these cases had the routine ultrasound scan performed in third trimester of pregnancy discovered a tumor mass, nor had it shown abnormal fetal movements. All had leg hypotonia detected on the first day of life. In all, both primary and intraspinal tumors responded well to chemotherapy. All survive with motor deficit and severe bladder dysfunction despite early physiotherapy. Scoliosis has developed in the case with the longest follow-up. The description of these patients enforces the importance of early diagnosis of tumor masses in late pregnancy. Neonatologists should be aware of this rare clinical entity and take it into account in the differential diagnosis with other conditions of early onset hypotonia. On the other hand, obstetric sonologists should be aware of the possibility to detect such rare tumors in late pregnancy, as anticipation of delivery may reduce the risk of late sequelae. PMID- 26901769 TI - Vesicoureteral Reflux and Renal Scarring Risk in Children after the First Febrile Urinary Tract Infection. AB - BACKGROUND/AIMS: There are many controversies regarding the best approach for evaluating children after their first febrile urinary tract infection (UTI). The aim of this study was to define the clinical, laboratory, and radiological features of patients with their first febrile UTI and to investigate the factors that might predict the presence of vesicoureteral reflux (VUR) and renal scarring. METHODS: The files of patients who were followed due to their first febrile UTI between 2008 and 2013 were retrospectively reviewed (n = 300). Patients were divided into groups based on their age, the resistance state of microorganisms, the presence of VUR, and scarring on Tc99m dimercaptosuccinic acid scintigraphy. The chi-square test and Mann-Whitney U test were used for analysis. RESULTS: The median age at the first febrile UTI was 11 months and girls constituted 77% of the patient population. VUR and renal scarring were detected in 30.9 and 19.4% of the patients, respectively. C-reactive protein levels and the presence of renal scarring were significantly higher in patients with VUR (p < 0.05). Abnormal ultrasonography findings, VUR and recurrent UTIs were significantly higher in patients with renal scars (p < 0.001). In multivariate analysis, we did not detect any factor that might predict the presence of VUR and renal scarring. CONCLUSION: A majority of children had their first febrile UTI at a young age. Although we could not find any factor that might predict the VUR and scar risk in patients with their first febrile UTI, an abnormal renal scan at 6 months after infection was closely related with the presence of VUR and recurrent UTIs. PMID- 26901770 TI - Predicting Aggressive Tendencies by Visual Attention Bias Associated with Hostile Emotions. AB - The goal of the current study is to clarify the relationship between social information processing (e.g., visual attention to cues of hostility, hostility attribution bias, and facial expression emotion labeling) and aggressive tendencies. Thirty adults were recruited in the eye-tracking study that measured various components in social information processing. Baseline aggressive tendencies were measured using the Buss-Perry Aggression Questionnaire (AQ). Visual attention towards hostile objects was measured as the proportion of eye gaze fixation duration on cues of hostility. Hostility attribution bias was measured with the rating results for emotions of characters in the images. The results show that the eye gaze duration on hostile characters was significantly inversely correlated with the AQ score and less eye contact with an angry face. The eye gaze duration on hostile object was not significantly associated with hostility attribution bias, although hostility attribution bias was significantly positively associated with the AQ score. Our findings suggest that eye gaze fixation time towards non-hostile cues may predict aggressive tendencies. PMID- 26901771 TI - Paper-based analytical devices for environmental analysis. AB - The field of paper-based microfluidics has experienced rapid growth over the past decade. Microfluidic paper-based analytical devices (MUPADs), originally developed for point-of-care medical diagnostics in resource-limited settings, are now being applied in new areas, such as environmental analyses. Low-cost paper sensors show great promise for on-site environmental analysis; the theme of ongoing research complements existing instrumental techniques by providing high spatial and temporal resolution for environmental monitoring. This review highlights recent applications of MUPADs for environmental analysis along with technical advances that may enable MUPADs to be more widely implemented in field testing. PMID- 26901772 TI - PRMT5-Mediated Methylation of NF-kappaB p65 at Arg174 Is Required for Endothelial CXCL11 Gene Induction in Response to TNF-alpha and IFN-gamma Costimulation. AB - Inflammatory agonists differentially activate gene expression of the chemokine family of proteins in endothelial cells (EC). TNF is a weak inducer of the chemokine CXCL11, while TNF and IFN-gamma costimulation results in potent CXCL11 induction. The molecular mechanisms underlying TNF plus IFN-gamma-mediated CXCL11 induction are not fully understood. We have previously reported that the protein arginine methyltransferase PRMT5 catalyzes symmetrical dimethylation of the NF kappaB subunit p65 in EC at multiple arginine residues. Methylation of Arg30 and Arg35 on p65 is critical for TNF induction of CXCL10 in EC. Here we show that PRMT5-mediated methylation of p65 at Arg174 is required for induction of CXCL11 when EC are costimulated with TNF and IFN-gamma. Knockdown of PRMT5 by RNAi reduced CXCL11 mRNA and protein levels in costimulated cells. Reconstitution of p65 Arg174Ala or Arg174Lys mutants into EC that were depleted of endogenous p65 blunted TNF plus IFN-gamma-mediated CXCL11 induction. Mass spectrometric analyses showed that p65 Arg174 arginine methylation is enhanced by TNF plus IFN-gamma costimulation, and is catalyzed by PRMT5. Chromatin immunoprecipitation assays (ChIP) demonstrated that PRMT5 is necessary for p65 association with the CXCL11 promoter in response to TNF plus IFN-gamma. Further, reconstitution of p65 Arg174Lys mutant in EC abrogated this p65 association with the CXCL11 promoter. Finally, ChIP and Re-ChIP assays revealed that symmetrical dimethylarginine containing proteins complexed with the CXCL11 promoter were diminished in p65 Arg174Lys-reconstituted EC stimulated with TNF and IFN-gamma. In total, these results indicate that PRMT5-mediated p65 methylation at Arg174 is essential for TNF plus IFN-gamma-mediated CXCL11 gene induction. We therefore suggest that the use of recently developed small molecule inhibitors of PRMT5 may present a therapeutic approach to moderating chronic inflammatory pathologies. PMID- 26901774 TI - Neutral-Type One-Dimensional Mixed-Valence Halogen-Bridged Platinum Chain Complexes with Large Charge-Transfer Band Gaps. AB - One-dimensional (1D) electronic systems have attracted significant attention for a long time because of their various physical properties. Among 1D electronic systems, 1D halogen-bridged mixed-valence transition-metal complexes (the so called MX chains) have been thoroughly studied owing to designable structures and electronic states. Here, we report the syntheses, structures, and electronic properties of three kinds of novel neutral MX-chain complexes. The crystal structures consist of 1D chains of Pt-X repeating units with (1R,2R)-(-) diaminocychlohexane and CN(-) in-plane ligands. Because of the absence of a counteranion, the neutral MX chains have short interchain distances, so that strong interchain electronic interaction is expected. Resonance Raman spectra and diffuse-reflectance UV-vis spectra indicate that their electronic states are mixed-valence states (charge-density-wave state: Pt(2+)...X-Pt(4+)-X...Pt(2+)...X Pt(4+)-X...). In addition, the relationship between the intervalence charge transfer (IVCT) band gap and the degree of distortion of the 1D chain shows that the neutral MX chains have a larger IVCT band gap than that of cationic MX-chain complexes. These results provide new insight into the physical and electronic properties of 1D chain compounds. PMID- 26901775 TI - Sediment Burial Intolerance of Marine Macroinvertebrates. AB - The marine environment contains suspended particulate matter which originates from natural and anthropogenic sources. Settlement of this material can leave benthic organisms susceptible to smothering, especially if burial is sudden i.e. following storms or activities such as dredging. Their survival will depend on their tolerance to, and their ability to escape from burial. Here we present data from a multi-factorial experiment measuring burial responses incorporating duration, sediment fraction and depth. Six macroinvertebrates commonly found in sediment rich environments were selected for their commercial and/or conservation importance. Assessments revealed that the brittle star (Ophiura ophiura), the queen scallop (Aequipecten opercularis) and the sea squirt (Ciona intestinalis) were all highly intolerant to burial whilst the green urchin (Psammichinus miliaris) and the anemone (Sagartiogeton laceratus), showed intermediate and low intolerance respectively, to burial. The least intolerant, with very high survival was the Ross worm (Sabellaria spinulosa). With the exception of C. intestinalis, increasing duration and depth of burial with finer sediment fractions resulted in increased mortality for all species assessed. For C. intestinalis depth of burial and sediment fraction were found to be inconsequential since there was complete mortality of all specimens buried for more than one day. When burial emergence was assessed O. ophiura emerged most frequently, followed by P. miliaris. The former emerged most frequently from the medium and fine sediments whereas P. miliaris emerged more frequently from coarse sediment. Both A. opercularis and S. laceratus showed similar emergence responses over time, with A. opercularis emerging more frequently under coarse sediments. The frequency of emergence of S. laceratus increased with progressively finer sediment and C. intestinalis did not emerge from burial irrespective of sediment fraction or depth. Finally, and perhaps unsurprisingly, the greatest ability to emerge from burial in all other species was from shallow (2 cm) burial. Although survival was consistently highly dependent on duration and depth of burial as expected, emergence behaviour was not as easily predictable thereby confounding predictions. We conclude that responses to burial are highly species specific and therefore tolerance generalisations are likely to be oversimplifications. These data may be used to inform environmental impact models that allow forecasting of the cumulative impacts of seabed disturbance and may provide mitigation measures for the sustainable use of the seabed. PMID- 26901773 TI - Early Life Factors and Inter-Country Heterogeneity in BMI Growth Trajectories of European Children: The IDEFICS Study. AB - BACKGROUND: Starting from birth, this explorative study aimed to investigate between-country differences in body mass index (BMI) trajectories and whether early life factors explain these differences. METHODS: The sample included 7,644 children from seven European countries (Belgium, Cyprus, Germany, Hungary, Italy, Spain, Sweden) participating in the multi-centre IDEFICS study. Information on early life factors and in total 53,409 repeated measurements of height and weight from 0 to <12 years of age were collected during the baseline (2007/2008) and follow-up examination (2009/2010) supplemented by records of routine child health visits. Country-specific BMI growth curves were estimated using fractional polynomial mixed effects models. Several covariates focussing on early life factors were added to the models to investigate their role in the between countries differences. RESULTS: Large between-country differences were observed with Italian children showing significantly higher mean BMI values at all ages >= 3 years compared to the other countries. For instance, at age 11 years mean BMI values in Italian boys and girls were 22.3 [21.9;22.8; 99% confidence interval] and 22.0 [21.5;22.4], respectively, compared to a range of 18.4 [18.1;18.8] to 20.3 [19.8;20.7] in boys and 18.2 [17.8;18.6] to 20.3 [19.8;20.7] in girls in the other countries. After adjustment for early life factors, differences between country-specific BMI curves became smaller. Maternal BMI was the factor being most strongly associated with BMI growth (p<0.01 in all countries) with associations increasing during childhood. Gestational weight gain (GWG) was weakly associated with BMI at birth in all countries. In some countries, positive associations between BMI growth and children not being breastfed, mothers' smoking during pregnancy and low educational level of parents were found. CONCLUSION: Early life factors seem to explain only some of the inter-country variation in growth. Maternal BMI showed the strongest association with children's BMI growth. PMID- 26901776 TI - Young Cervical Cancer Patients May Be More Responsive than Older Patients to Neoadjuvant Chemotherapy Followed by Radical Surgery. AB - OBJECTIVE: To evaluate the effects of age and the clinical response to neoadjuvant chemotherapy (NACT) in patients with cervical cancer who received neoadjuvant chemotherapy followed by radical surgery. METHODS: A total of 1,014 patients with advanced cervical cancer who received NACT followed by radical surgery were retrospectively selected. Patients were divided into young (aged <=35 years, n = 177) and older (aged >35 years, n = 837) groups. We compared the short-term responses and survival rates between the groups. The five-year disease free survival (DFS) and overall survival (OS) rates were stratified by age, NACT response, and FIGO stage. RESULTS: The overall response rate was 86.8% in the young group and 80.9% in the older group. The young patients had an earlier FIGO stage (P<0.001), a higher rate of adenocarcinoma (P = 0.022), and more lymph node metastasis (P = 0.033) than the older patients. The presence of adenocarcinoma as the histological type (P = 0.024) and positive lymph node metastasis (P<0.001) were identified as independent risk factors for survival. When stratified by age and clinical response, young patients with no response to NACT had a worse clinicopathological condition compared with the other subgroups. Compared with non-responders, responders to NACT had a higher five-year DFS rate (80.1% versus 71.8%; P = 0.019) and OS rate (82.6% versus 71.8%; P = 0.003) among the young patients but not among the older patients. CONCLUSIONS: Responders to NACT aged 35 years or younger benefitted the most from NACT, while the young non-responders benefitted the least. Age might represent an important factor to consider when performing NACT in patients with cervical cancer. PMID- 26901777 TI - Latino immigrant day laborer perceptions of occupational safety and health information preferences. AB - BACKGROUND: We address immigrant day laborers' experiences with occupational safety in the construction industry in New Orleans, and opinions about content and method of communication for educational interventions to reduce occupational risks. METHODS: In 2011, we conducted seven focus groups with 48 Spanish-speaking day laborers (8 women, 40 men, 35 years on average). Focus group results are based on thematic analysis. RESULTS: Most employers did not provide safety equipment, threatened to dismiss workers who asked for it, and did not provide health insurance. Attitudes toward accepting unsafe work conditions varied. Women faced lower pay and hiring difficulties than men. Day laborers preferred audio format over written, and content about consequences from and equipment for different jobs/exposures. CONCLUSIONS: Day laborers have common occupational experiences, but differences existed by gender, literacy and sense of control over safety. Day laborer information preferences and use of media needs further studying. Am. J. Ind. Med. 59:476-485, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26901779 TI - Correction: Periconceptional Heat Stress of Holstein Dams Is Associated with Differences in Daughter Milk Production and Composition during Multiple Lactations. PMID- 26901780 TI - Photoacidic and Photobasic Behavior of Transition Metal Compounds with Carboxylic Acid Group(s). AB - Excited state proton transfer studies of six Ru polypyridyl compounds with carboxylic acid/carboxylate group(s) revealed that some were photoacids and some were photobases. The compounds [Ru(II)(btfmb)2(LL)](2+), [Ru(II)(dtb)2(LL)](2+), and [Ru(II)(bpy)2(LL)](2+), where bpy is 2,2'-bipyridine, btfmb is 4,4'-(CF3)2 bpy, and dtb is 4,4'-((CH3)3C)2-bpy, and LL is either dcb = 4,4'-(CO2H)2-bpy or mcb = 4-(CO2H),4'-(CO2Et)-2,2'-bpy, were synthesized and characterized. The compounds exhibited intense metal-to-ligand charge-transfer (MLCT) absorption bands in the visible region and room temperature photoluminescence (PL) with long tau > 100 ns excited state lifetimes. The mcb compounds had very similar ground state pKa's of 2.31 +/- 0.07, and their characterization enabled accurate determination of the two pKa values for the commonly utilized dcb ligand, pKa1 = 2.1 +/- 0.1 and pKa2 = 3.0 +/- 0.2. Compounds with the btfmb ligand were photoacidic, and the other compounds were photobasic. Transient absorption spectra indicated that btfmb compounds displayed a [Ru(III)(btfmb(-))L2](2+)* localized excited state and a [Ru(III)(dcb(-))L2](2+)* formulation for all the other excited states. Time dependent PL spectral shifts provided the first kinetic data for excited state proton transfer in a transition metal compound. PL titrations, thermochemical cycles, and kinetic analysis (for the mcb compounds) provided self-consistent pKa* values. The ability to make a single ionizable group photobasic or photoacidic through ligand design was unprecedented and was understood based on the orientation of the lowest-lying MLCT excited state dipole relative to the ligand that contained the carboxylic acid group(s). PMID- 26901778 TI - Rho Kinase ROCK2 Mediates Acid-Induced NADPH Oxidase NOX5-S Expression in Human Esophageal Adenocarcinoma Cells. AB - Mechanisms of the progression from Barrett's esophagus (BE) to esophageal adenocarcinoma (EA) are not fully understood. We have shown that NOX5-S may be involved in this progression. However, how acid upregulates NOX5-S is not well known. We found that acid-induced increase in NOX5-S expression was significantly decreased by the Rho kinase (ROCK) inhibitor Y27632 in BE mucosal biopsies and FLO-1 EA cells. In addition, acid treatment significantly increased the Rho kinase activity in FLO-1 cells. The acid-induced increase in NOX5-S expression and H2O2 production was significantly decreased by knockdown of Rho kinase ROCK2, but not by knockdown of ROCK1. Conversely, the overexpression of the constitutively active ROCK2, but not the constitutively active ROCK1, significantly enhanced the NOX5-S expression and H2O2 production. Moreover, the acid-induced increase in Rho kinase activity and in NOX5-S mRNA expression was blocked by the removal of calcium in both FLO-1 and OE33 cells. The calcium ionophore A23187 significantly increased the Rho kinase activity and NOX5-S mRNA expression. We conclude that acid-induced increase in NOX5-S expression and H2O2 production may depend on the activation of ROCK2, but not ROCK1, in EA cells. The acid-induced activation of Rho kinase may be mediated by the intracellular calcium increase. It is possible that persistent acid reflux present in BE patients may increase the intracellular calcium, activate ROCK2 and thereby upregulate NOX5-S. High levels of reactive oxygen species derived from NOX5-S may cause DNA damage and thereby contribute to the progression from BE to EA. PMID- 26901781 TI - Activity of selected hydrolytic enzymes in Allium sativum L. anthers. AB - The aim of the study was to determine enzymatic activity in sterile Allium sativum anthers in the final stages of male gametophyte development (the stages of tetrads and free microspores). The analysed enzymes were shown to occur in the form of numerous isoforms. In the tetrad stage, esterase activity was predominant, which was manifested by the greater number of isoforms of the enzyme. In turn, in the microspore stage, higher numbers of isoforms of acid phosphatases and proteases were detected. The development of sterile pollen grains in garlic is associated with a high level of protease and acid phosphatase activity and lower level of esterase activities in the anther locule. Probably this is the first description of the enzymes activity (ACPH, EST, PRO) in the consecutives stages of cell wall formation which is considered to be one of the causes of male sterility in flowering plant. PMID- 26901783 TI - Correction: Development of a Quantitative Food Frequency Questionnaire for Use among the Yup'ik People of Western Alaska. PMID- 26901782 TI - Overexpression of an F-box protein gene disrupts cotyledon vein patterning in Arabidopsis. AB - Plant vascular patterning is complex. However, the detailed molecular mechanism of vascular patterning is still unknown. In this study, FBXL, an Arabidopsis F box motif gene, was isolated by using 3' rapid amplification of cDNA ends (RACE) technique. The gene contained a coding sequence of 1407 nucleotides coding 468 amino acid residues. Amino acid sequence analysis revealed that the gene encoded a protein harboring an F-box motif at the N terminus, an LRRs motif in the middle, and an FBD motif at the C terminus. FBXL promoter-beta-glucuronidase (GUS) and 35S promoter-FBXL vectors were constructed and transformed into Arabidopsis thaliana to understand the function of the FBXL gene. GUS expression analysis indicated that FBXL was specifically expressed in the vascular tissues of the root, stem, leaf, and inflorescence. FBXL overexpression in Arabidopsis displayed an abnormal venation pattern in cotyledons. Furthermore, FBXL expression was not induced by exogenous auxin and its transcript accumulation did not overlap with the distribution of endogenous auxin. These results suggested that FBXL may be involved in cotyledon vein patterning via auxin-independent pathway. PMID- 26901784 TI - Pharmaco-EEG, Pharmaco-Sleep and EEG-Based Personalized Medicine. PMID- 26901785 TI - Delayed Time-to-Treatment of an Antisense Morpholino Oligomer Is Effective against Lethal Marburg Virus Infection in Cynomolgus Macaques. AB - Marburg virus (MARV) is an Ebola-like virus in the family Filovirdae that causes sporadic outbreaks of severe hemorrhagic fever with a case fatality rate as high as 90%. AVI-7288, a positively charged antisense phosphorodiamidate morpholino oligomer (PMOplus) targeting the viral nucleoprotein gene, was evaluated as a potential therapeutic intervention for MARV infection following delayed treatment of 1, 24, 48, and 96 h post-infection (PI) in a nonhuman primate lethal challenge model. A total of 30 cynomolgus macaques were divided into 5 groups of 6 and infected with 1,830 plaque forming units of MARV subcutaneously. AVI-7288 was administered by bolus infusion daily for 14 days at 15 mg/kg body weight. Survival was the primary endpoint of the study. While none (0 of 6) of the saline group survived, 83-100% of infected monkeys survived when treatment was initiated 1, 24, 48, or 96 h post-infection (PI). The antisense treatment also reduced serum viremia and inflammatory cytokines in all treatment groups compared to vehicle controls. The antibody immune response to virus was preserved and tissue viral antigen was cleared in AVI-7288 treated animals. These data show that AVI 7288 protects NHPs against an otherwise lethal MARV infection when treatment is initiated up to 96 h PI. PMID- 26901786 TI - Molecular Characterization of Coccidia Associated with an Epizootic in Green Sea Turtles (Chelonia mydas) in South East Queensland, Australia. AB - In the spring of 2014, mass mortalities among wild green sea turtles occurred off the coast of south-east Queensland, Australia. The suspected causative agent was Caryospora cheloniae, an eimeriid coccidian implicated in previous epizootics. Necropsies were undertaken on a subset of 11 dead turtles, with subsequent histopathology and molecular analyses. All turtles returned positive PCR results for coccidial infection in various tissues; these included the brain, gastrointestinal tract, lung, kidney and thyroid. Granulomatous encephalitis was consistently observed, as well as enteritis and, less frequently, thyroiditis and nephritis. Sequencing and phylogenetic analyses indicated the presence of two distinct coccidian genotypes, presumably separate species-one associated with the brain, gastrointestinal tract and lung, and the second with the thyroid and kidney. Maximum likelihood and Bayesian inference analyses placed the first genotype closest to the lankesterellid genus Schellackia, rather than in the Eimeriidae, while the second was paraphyletic to the eimeriids. Presence of coccidial stages in extra-intestinal tissues of the primary host raises questions about the potential presence of intermediate or paratenic hosts within the life cycles, as well as their current placement relative to the genus Caryospora. This study represents the first genetic characterization of this emerging disease agent in green sea turtles, an endangered species, and has relevance for life cycle elucidation and future development of diagnostics. PMID- 26901787 TI - Intramyocardial transplantation of mesenchymal stromal cells for chronic myocardial ischemia and impaired left ventricular function: Results of the MESAMI 1 pilot trial. AB - BACKGROUND: The MESAMI 1 trial was a bicentric pilot study designed to test the feasibility and safety of intramyocardially injected autologous bone marrow derived mesenchymal stromal cells (MSCs) for the treatment of ischemic cardiomyopathy. METHODS AND RESULTS: The study included 10 patients with chronic myocardial ischemia, left ventricular (LV) ejection fractions (EFs) of <=35%, and reversible perfusion defects who were on stable optimal medical therapy and were not candidates for revascularization. MSCs (mean: 61.5*10(6) cells per patient) were injected into 10-16 viable sites at the border of the LV scar via a NOGA guided catheter. Both primary endpoints, feasibility (successful harvest, expansion, and injection of autologous MSCs) and safety (absence of severe adverse events [SAEs]) were met in all 10 patients at the 1-month follow-up time point, and none of the SAEs reported during the full 2-year follow-up period were attributable to the study intervention. The results of secondary efficacy endpoint analyses identified significant improvements from baseline to Month 12 in LVEF (29.4+/-2.0% versus 35.7+/-2.5%; p=0.003), LV end-systolic volume (167.8+/-18.8mL versus 156.1+/-28.6mL; p=0.04), 6-min walk test and NYHA functional class. CONCLUSIONS: Our results suggest that autologous MSCs can be safely administered to the hearts of patients with severe, chronic, reversible myocardial ischemia and impaired cardiac function and may be associated with improvements in cardiac performance, LV remodeling, and patient functional status. A randomized, double blind, multicenter, placebo-controlled clinical trial (MESAMI 2) will evaluate the efficacy of this treatment approach in a larger patient population. CLINICAL TRIAL REGISTRATION: Unique identifier: NCT01076920. PMID- 26901788 TI - Bicuspid aortic valve complicated by pseudo-aneurysm of aortic root abscess. PMID- 26901789 TI - AGTR1 has undergone natural selection in Euro-Asian populations in relation to ambient temperature that predisposes Chinese populations to essential hypertension. PMID- 26901790 TI - Hyaluronidase 2 deficiency is a molecular cause of cor triatriatum sinister in mice. PMID- 26901791 TI - A New Tool for Transbronchial Cryobiopsies in the Lung: An Experimental Feasibility ex vivo Study. AB - BACKGROUND: Transbronchial cryobiopsy (TBCB) is a minimally invasive procedure to establish a diagnosis of interstitial lung disease though with the disadvantage that samples have to be extracted together with the bronchoscope. OBJECTIVES: The aim of the present study was to evaluate the feasibility of a new cryoprobe with which biopsy samples can be obtained through the working channel of the flexible bronchoscope. METHODS: The feasibility of obtaining transbronchial specimens with TBCB was tested and the technique was compared to transbronchial forceps biopsy (TBFB) in a prospectively randomized ex vivo animal study using a standard flexible bronchoscopy technique. The rate of successful biopsies and the duration of the sampling procedure were recorded for both methods. Size and quality of the biopsies were histologically evaluated and measured. RESULTS: Biopsy samples could be obtained in 93.3% of TBCB and in 79.0% of TBFB procedures (p = 0.182). Sampling procedure time did not differ in any clinically relevant manner between the two methods. The mean specimen area of TBCB samples was significantly higher compared to that of TBFB samples (8.08 +/- 5.80 vs. 2.61 +/- 2.14 mm2; p < 0.0001). TBCB specimens showed less artifacts and a significantly higher percentage of alveolar tissue (53.57 vs. 25.42%; p = 0.0285) than TBFB specimens. CONCLUSIONS: It is feasible to retrieve TBCB samples of good quality and size with the new mini cryoprobe through the working channel of the bronchoscope, while the bronchoscope remains within the central airways throughout the whole procedure. Further studies are necessary to evaluate the safety and efficacy in an in vivo setting. PMID- 26901792 TI - A systematic review and meta-analysis of the association between the apolipoprotein E genotype and delirium. AB - The role of apolipoprotein E (APOE) in Alzheimer's disease and other dementias has been investigated intensively. However, the relationship between APOE and delirium has only recently been explored in studies that have included relatively small samples. A meta-analysis of the published pooled data is timely to explore the relationship between APOE and delirium and to inform further research in this topic. PubMed, EBSCOhost, Google Scholar, Scopus, all EBM Reviews (OVID) and the Cochrane Database of Systematic Reviews were searched with relevant keywords and from the references of relevant papers. Ten papers were found that examined the relationship between APOE and delirium. Data were extracted from eight of them and pooled for meta-analysis using random effects with R software. Data from 1762 participants, of whom 479 (27.2%) were diagnosed with delirium, showed low heterogeneity (Q=13.11, d.f.=7, P=0.07; I=44.86%). The possession of the APOE epsilon4 allele has a small (log odds ratio: 0.18, 95% confidence interval: 0.23 0.59), nonsignificant (P=0.38) effect on the presence of delirium. No publication bias was identified. The metapower of the pooled data was low (alpha=0.05, power=0.65). On analysing the studies to date, it seems that there is no association between APOE and the occurrence of delirium. We suggest that further studies are needed with greater number of patients to clarify any association as well as to examine for other patterns of association including relevance for subgroups of patients who develop delirium and for effects on the phenotype of delirium and the outcomes. PMID- 26901793 TI - Complex genomic variants contribute toward the genetic architecture of autism spectrum disorder. AB - Genetic factor plays a critical role in the etiology of autism spectrum disorder (ASD). Both common variants with a small effect and rare mutations with a large effect contribute toward the genetic basis of ASD, showing the high genetic heterogeneity of ASD. Genomic rearrangements account for around 10-15% of its genetic landscape. However, they are highly individualized and each of them has a very rare frequency. PMID- 26901794 TI - Genetic variant analysis of the putative regulatory regions of the LRRC7 gene in bipolar disorder. PMID- 26901796 TI - Respiratory viruses as a cause of sudden death. PMID- 26901795 TI - Trends in CD4 Count Testing, Retention in Pre-ART Care, and ART Initiation Rates over the First Decade of Expansion of HIV Services in Haiti. AB - BACKGROUND: High attrition during the period from HIV testing to antiretroviral therapy (ART) initiation is widely reported. Though treatment guidelines have changed to broaden ART eligibility and services have been widely expanded over the past decade, data on the temporal trends in pre-ART outcomes are limited; such data would be useful to guide future policy decisions. METHODS: We evaluated temporal trends and predictors of retention for each step from HIV testing to ART initiation over the past decade at the GHESKIO clinic in Port-au-Prince Haiti. The 24,925 patients >17 years of age who received a positive HIV test at GHESKIO from March 1, 2003 to February 28, 2013 were included. Patients were followed until they remained in pre-ART care for one year or initiated ART. RESULTS: 24,925 patients (61% female, median age 35 years) were included, and 15,008 (60%) had blood drawn for CD4 count within 12 months of HIV testing; the trend increased over time from 36% in Year 1 to 78% in Year 10 (p<0.0001). Excluding transfers, the proportion of patients who were retained in pre-ART care or initiated ART within the first year after HIV testing was 84%, 82%, 64%, and 64%, for CD4 count strata <=200, 201 to 350, 351 to 500, and >500 cells/mm3, respectively. The trend increased over time for each CD4 strata, and in Year 10, 94%, 95%, 79%, and 74% were retained in pre-ART care or initiated ART for each CD4 strata. Predictors of pre-ART attrition included male gender, low income, and low educational status. Older age and tuberculosis (TB) at HIV testing were associated with retention in care. CONCLUSIONS: The proportion of patients completing assessments for ART eligibility, remaining in pre-ART care, and initiating ART have increased over the last decade across all CD4 count strata, particularly among patients with CD4 count <=350 cells/mm3. However, additional retention efforts are needed for patients with higher CD4 counts. PMID- 26901798 TI - The free serratus anterior artery perforator flap-A case report and anatomic study. AB - We report a reconstructive case using a free serratus anterior artery perforator flap and an anatomic study. A 50-year-old man with upper esophageal sphincter stricture underwent segmental cervical esophageal resection. The size of the defect was approximately 5.5 cm. We then performed esophageal reconstruction using the free serratus anterior artery perforator flap. Esophagography performed on postoperative day 7 revealed no definite leakage and a viable anastomosis site with wide patency. No complications developed during the long-term follow-up period of 3 years. We reviewed the literature and performed an anatomic study using four fresh cadavers. We performed an angiographic study using two specimens and dissection of this perforator using other two specimens. We found that a direct connection existed between the serratus anterior artery and intercostal perforator to the skin in two of eight chests. The connection was located at the 4th intercostal space in the left chest of one cadaver and at the 6th/7th intercostal space in the left chest of the other cadaver. The free serratus anterior artery perforator flap is a new flap that could be considered for use during the elevation of a perforator flap in the lateral chest area, and especially in the area overlying the serratus anterior muscle. (c) 2016 Wiley Periodicals, Inc. Microsurgery 36:339-344, 2016. PMID- 26901797 TI - An Unusual Member of the Papain Superfamily: Mapping the Catalytic Cleft of the Marasmius oreades agglutinin (MOA) with a Caspase Inhibitor. AB - Papain-like cysteine proteases (PLCPs) constitute the largest group of thiol based protein degrading enzymes and are characterized by a highly conserved fold. They are found in bacteria, viruses, plants and animals and involved in a number of physiological and pathological processes, parasitic infections and host defense, making them interesting targets for drug design. The Marasmius oreades agglutinin (MOA) is a blood group B-specific fungal chimerolectin with calcium dependent proteolytic activity. The proteolytic domain of MOA presents a unique structural arrangement, yet mimicking the main structural elements in known PLCPs. Here we present the X-ray crystal structure of MOA in complex with Z-VAD fmk, an irreversible caspase inhibitor known to cross-react with PLCPs. The structural data allow modeling of the substrate binding geometry and mapping of the fundamental enzyme-substrate interactions. The new information consolidates MOA as a new, yet strongly atypical member of the papain superfamily. The reported complex is the first published structure of a PLCP in complex with the well characterized caspase inhibitor Z-VAD-fmk. PMID- 26901799 TI - Spatial environmental heterogeneity affects plant growth and thermal performance on a green roof. AB - Green roofs provide ecosystem services, including stormwater retention and reductions in heat transfer through the roof. Microclimates, as well as designed features of green roofs, such as substrate and vegetation, affect the magnitude of these services. Many green roofs are partially shaded by surrounding buildings, but the effects of this within-roof spatial environmental heterogeneity on thermal performance and other ecosystem services have not been examined. We quantified the effects of spatial heterogeneity in solar radiation, substrate depth and other variables affected by these drivers on vegetation and ecosystem services in an extensive green roof. Spatial heterogeneity in substrate depth and insolation were correlated with differential growth, survival and flowering in two focal plant species. These effects were likely driven by the resulting spatial heterogeneity in substrate temperature and moisture content. Thermal performance (indicated by heat flux and substrate temperature) was influenced by spatial heterogeneity in vegetation cover and substrate depth. Areas with less insolation were cooler in summer and had greater substrate moisture, leading to more favorable conditions for plant growth and survival. Spatial variation in substrate moisture (7%-26% volumetric moisture content) and temperature (21 degrees C-36 degrees C) during hot sunny conditions in summer could cause large differences in stormwater retention and heat flux within a single green roof. Shaded areas promote smaller heat fluxes through the roof, leading to energy savings, but lower evapotranspiration in these areas should reduce stormwater retention capacity. Spatial heterogeneity can thus result in trade-offs between different ecosystem services. The effects of these spatial heterogeneities are likely widespread in green roofs. Structures that provide shelter from sun and wind may be productively utilized to design higher functioning green roofs and increase biodiversity by providing habitat heterogeneity. PMID- 26901800 TI - Changes in rhizosphere bacterial gene expression following glyphosate treatment. AB - In commercial agriculture, populations and interactions of rhizosphere microflora are potentially affected by the use of specific agrichemicals, possibly by affecting gene expression in these organisms. To investigate this, we examined changes in bacterial gene expression within the rhizosphere of glyphosate tolerant corn (Zea mays) and soybean (Glycine max) in response to long-term glyphosate (PowerMAXTM, Monsanto Company, MO, USA) treatment. A long-term glyphosate application study was carried out using rhizoboxes under greenhouse conditions with soil previously having no history of glyphosate exposure. Rhizosphere soil was collected from the rhizoboxes after four growing periods. Soil microbial community composition was analyzed using microbial phospholipid fatty acid (PLFA) analysis. Total RNA was extracted from rhizosphere soil, and samples were analyzed using RNA-Seq analysis. A total of 20-28 million bacterial sequences were obtained for each sample. Transcript abundance was compared between control and glyphosate-treated samples using edgeR. Overall rhizosphere bacterial metatranscriptomes were dominated by transcripts related to RNA and carbohydrate metabolism. We identified 67 differentially expressed bacterial transcripts from the rhizosphere. Transcripts downregulated following glyphosate treatment involved carbohydrate and amino acid metabolism, and upregulated transcripts involved protein metabolism and respiration. Additionally, bacterial transcripts involving nutrients, including iron, nitrogen, phosphorus, and potassium, were also affected by long-term glyphosate application. Overall, most bacterial and all fungal PLFA biomarkers decreased after glyphosate treatment compared to the control. These results demonstrate that long-term glyphosate use can affect rhizosphere bacterial activities and potentially shift bacterial community composition favoring more glyphosate-tolerant bacteria. PMID- 26901802 TI - Are the ratios of the two concentrations at steady state in the medium pairs of air-water, air-soil, water-soil, water-sediment, and soil-sediment? AB - For optimization and evaluation of a steady state multimedia model, concurrent multimedia monitoring data of steady state are necessary. In the lack of emission rate information, the primary aim of the present work was to assess if five concentration ratios (CRs) (C water/Cair, C soil/Cair, C sediment/C soil, C water/C soil, and C sediment/C water) of chemical compounds are at steady state in South Korea. A total of 16,676 CRs values were calculated using 74,641 concurrent multimedia (air, water, soil and sediment) monitoring data from 96 areas for 45 semi-volatile organic compounds (polychlorinated dibenzo-p dioxins/furans, polybrominated diphenyl ethers, phthalates, and polycyclic aromatic hydrocarbons). Test of steady state indicated that CR is statistically at steady state with an overall occurrence rate of 70% of the 223 tested cases while the rates of individual chemical groups were 94.5%, 88%, 82.5%, and 37.6% for polycyclic aromatic hydrocarbons, phthalates, polybrominated diphenyl ethers, and polychlorinated dibenzo-p-dioxins/furans, respectively. About 83% of the steady state CRs resulted from scattering of two concentrations in each of the medium pairs without a certain temporal trend while the rest due to closely co varying two concentrations. Analysis of the 95% confidence interval of the fugacity ratio indicated that CRs at steady state may occur in equilibrium state with higher chances than CRs at unsteady state. A total of 156 point values representing the CRs at steady state were determined that can be used for optimization and evaluation of steady state one-box multimedia models. However, potential influences of the uncertainties of the values arisen from the scattering of the concentration data should quantitatively be assessed in the model optimization and evaluation. PMID- 26901801 TI - Pollutant flows from a phosphogypsum disposal area to an estuarine environment: An insight from geochemical signatures. AB - Phosphogypsum wastes from phosphate fertilizer industries are stockpiled in stacks with high contamination potential. An assessment of the environmental impact, including the use of geochemical tracers such as rare earth elements (REE) and Cl/Br ratios, was carried out in the phosphogypsum stack located at the Estuary of Huelva (SW Spain). Inside the pile, highly polluted acid pore-waters flows up to the edge of the stack, emerging as small fluvial courses, known as edge outflows, which discharge directly into the estuary. The disposal area is divided into four zones; two unrestored zones with surface ponds of industrial process water and two a priori already-restored zones. However, an extensive sampling of edge outflows conducted in the perimeter of the four zones demonstrates the high potential of contamination of the whole stack, including those zones that were supposedly restored. These solutions are characterized by a pH of 1.9 and concentrations of 6100 mg/L for P, 1970 mg/L for S, 600 mg/L for F, 200mg/L for NH4(+), 100mg/L for Fe, 10-30 mg/L for Zn, As and U, and 1-10mg/L for Cr, Cu and Cd. Preliminary restoration actions and those planned for the future prioritize removal of ponded process water and cover of the phosphogypsum with artificial topsoil. These actions presuppose that the ponded process water percolates through the porous medium towards the edge up to reach the estuary. However, geochemical tracers rule out this connection and point to an estuarine origin for these leachates, suggesting a possible tidal-induced leaching of the waste pile in depth. These findings would explain the ineffectiveness of preliminary restoration measures and should be considered for the development of new action plans. PMID- 26901803 TI - Effects of polybrominated diphenyl ethers and plant species on nitrification, denitrification and anammox in mangrove soils. AB - Little is known about polybrominated diphenyl ethers (PBDEs) and planting affect biogeochemical processes, and their impact on microbial nitrogen (N) transformation in soil. A 12-month microcosm experiment was conducted to understand the effects of a mixture of PBDEs at two contamination levels, 2 and 20 mg kg(-1)dry weight representing low and high soil contamination, respectively, using two mangrove plant species, namely Kandelia obovata (Ko) and Bruguiera gymnorrhiza (Bg), on nitrification, denitrification and anammox in mangrove soils. No significant changes in these N transformation processes were found at month 3 and at a low level of PBDEs in both plant species, suggesting that short-term exposure to 2 mg kg(-1) contamination did not affect microbial N transformation. At month 12, a high level of PBDE contamination significantly decreased the nitrification potential activity and the copy numbers of archaeal amoA and bacterial amoA gene in Ko soil, but such inhibitory effect was not significant in Bg soil. On the contrary, the denitrification-related parameters, including the activities of nitrate reductase and nitrite reductase, potential denitrification activity and copy numbers of nirK, nirS and nosZ gene, were stimulated by a high level of PBDE contamination in both Ko and Bg soils, and the stimulation was higher in the more anaerobic Bg soil. Different from denitrification, a high level of PBDE contamination decreased the copy numbers of anammox bacterial 16S rRNA gene in Bg soil but not in Ko soil; this was possibly related to the lower nitrate concentration in Bg soil that might inhibit the growth of anammox bacteria. These results indicated that the effects of PBDEs on microbial N transformation were plant species-specific, with the nitrifying microorganisms in Ko soil more susceptible to PBDE contamination, while denitrification and anammox in Bg soil were more sensitive. PMID- 26901804 TI - Beyond the conventional life cycle inventory in wastewater treatment plants. AB - The conventional approach for the environmental assessment of wastewater treatment plants (WWTPs) is typically based on the removal efficiency of organic load and nutrients as well as the quantification of energy and chemicals consumption. Current wastewater treatment research entails the monitoring of direct emissions of greenhouse gases (GHG) and emerging pollutants such as pharmaceutical and personal care products (PPCPs), which have been rarely considered in the environmental assessment of a wastewater treatment facility by life cycle assessment (LCA) methodology. As a result of that, the real environmental impacts of a WWTP may be underestimated. In this study, two WWTPs located in different climatic regions (Atlantic and Mediterranean) of Spain were evaluated in extensive sampling campaigns that included not only conventional water quality parameters but also direct GHG emissions and PPCPs in water and sludge lines. Regarding the GHG monitoring campaign, on-site measurements of methane (CH4) and nitrous oxide (N2O) were performed and emission factors were calculated for both WWTPs. GHG direct emissions accounted for 62% of the total global warming potential (GWP), much more relevant than indirect CO2 emissions associated with electricity use. Regarding PPCPs, 19 compounds were measured in the main streams: influent, effluent and sludge, to perform the evaluation of the toxicity impact categories. Although the presence of heavy metals in the effluent and the sludge as well as the toxicity linked to the electricity production may shade the toxicity impacts linked to PPCPs in some impact categories, the latter showed a notable influence on freshwater ecotoxicity potential (FETP). For this impact category, the removal of PPCPs within the wastewater treatment was remarkably important and arose as an environmental benefit in comparison with the non-treatment scenario. PMID- 26901805 TI - Widespread somatosensory sensitivity in naturally occurring canine model of osteoarthritis. AB - Osteoarthritis (OA)-associated pain is a leading cause of disability. Central sensitization (CS), as a result of OA, is recognized as an important facet of human patients' chronic pain and has been measured in people using quantitative sensory testing (QST) testing. The spontaneous canine OA model has been suggested as a good translational model, but CS has not been explored in this model. In this study, QST was performed on dogs with and without spontaneous hip or stifle OA to determine whether OA is associated with CS in this model. Mechanical (von Frey and blunt pressure) and thermal (hot and cold) sensory thresholds obtained in dogs with chronic OA-associated pain (n = 31) were compared with those of normal dogs (n = 23). Dogs were phenotyped and joint-pain scored, and testing was performed at the OA-affected joint, cranial tibial muscle, and dorsal metatarsal region. QST summary data were evaluated using mixed-effect models to understand the influence of OA status and covariates, and dogs with OA and control dogs were compared. The presence of OA was strongly associated with hyperalgesia across all QST modalities at the index joint, cranial tibial muscle, and metatarsal site. Mechanical QST scores were significantly moderately negatively correlated with total joint-pain scores. The spontaneous canine OA model is associated with somatosensory sensitivity, likely indicative of CS. These data further validate the canine spontaneous OA model as an appropriate model of the human OA pain condition. PMID- 26901806 TI - Chronic pain in adolescence and internalizing mental health disorders: a nationally representative study. AB - Chronic pain in childhood and adolescence has been shown to heighten the risk for depressive and anxiety disorders in specific samples in adulthood; however, little is known about the association between a wider variety of chronic pains and internalizing mental health disorders. Using nationally representative data, the objectives of this study were to establish prevalence rates of internalizing mental health disorders (anxiety and depressive disorders) among cohorts with or without adolescent chronic pain, and to examine whether chronic pain in adolescence is associated with lifetime history of internalizing mental health disorders reported in adulthood. Data from the National Longitudinal Study of Adolescent to Adult Health (Add Health) was used (N = 14,790). Individuals who had chronic pain in adolescence subsequently reported higher rates of lifetime anxiety disorders (21.1% vs 12.4%) and depressive disorders (24.5% vs 14.1%) in adulthood as compared with individuals without a history of adolescent chronic pain. Multivariate logistic regression confirmed that chronic pain in adolescence was associated with an increased likelihood of lifetime history of anxiety disorders (odds ratio: 1.33; 95% confidence interval: 1.09-1.63, P = 0.005) and depressive disorders (odds ratio: 1.38; confidence interval: 1.16-1.64, P < 0.001) reported in adulthood. Future research is needed to examine neurobiological and psychological mechanisms underlying these comorbidities. PMID- 26901808 TI - Angiopoietins in the bone marrow microenvironment of acute lymphoblastic leukemia. AB - OBJECTIVE: Angiogenesis have implications in leukemia biology. Angiopoietin 1 (Ang 1) is an angiogenic cytokine which is essential in survival and proliferation of endothelial cells. Angiopoietin 2 (Ang 2) promotes dissociation of pericytes and increases vascular permeability and stromal derived factor 1 alpha (SDF 1alpha) which is a key player in stem cell traffic in the bone marrow (BM), has stimulating effects on angiogenesis as well. Here, we investigated the role of the leukemic BM microenvironment and specifically, the role of SDF 1alpha CXCR4 and Ang 1/Ang 2-Tie 2 axes. METHODS: Here, Ang 1, Ang 2, and SDF 1alpha levels were measured in the BM plasma and in supernatants of mesenchymal stem/stromal cells (MSCs) of patients with ALL and compared with those of healthy controls. RESULTS: The results showed that at diagnosis, BM plasma levels of Ang 1 and SDF 1alpha were significantly low and Ang 2 was high when compared to control values. Remission induction was associated with an increase in Ang 1/Ang 2 ratio and SDF levels in BM plasma. DISCUSSION: The results suggest that BM microenvironment and leukemic cell-stroma interaction influences the secretion of Ang 1, 2 and SDF 1alpha, thus, may affect both angiogenesis, homing and mobilization of leukemic blasts. PMID- 26901807 TI - Demoralization in Cancer Patients and Related Factors in Taiwan. AB - BACKGROUND: Demoralization frequently occurs in hospice, cancer, and critically ill patients. Severe demoralization can lead to suicidal ideation, making this issue of great import to healthcare providers. OBJECTIVE: The aim of this study is to inform nursing professionals of the risk factors of demoralization in cancer patients via investigating its relationship with cancer patients' demographic data and disease characteristics. METHODS: This is a cross-sectional descriptive study using a structured questionnaire including assessments of demographic data and disease characteristics, as well as the Demoralization Scale Mandarin version. Univariate logistic regression was used to explore the relations between demoralization and these other variables. RESULTS: The mean (SD) Demoralization Scale Mandarin version score was 30.08 (13.68) (range, 0-73). Demoralization was significantly related to age (r = 0.1, P = .050), marital status (r = 0.11, P = .034), education (r = 0.17, P < .001), monthly income (r = 0.22, P < .001), disease status (r = 0.10, P = .050), and treatment type (r = 0.12, P = .014). CONCLUSIONS: This study demonstrates the factors influencing demoralization among cancer patients. Future studies might expand to include patients with other chronic or critical illnesses or disadvantaged groups to better understand the prevalence of demoralization. This would help draw more attention from clinical healthcare providers, healthcare institutions, and other healthcare authorities to demoralization. IMPLICATIONS OR PRACTICE: The results provide reference data for nursing professionals about the care of cancer patients. PMID- 26901809 TI - Does a selection interview predict year 1 performance in dental school? AB - : It is important for dental schools to select students who will complete their degree and progress on to become the dentists of the future. The process should be transparent, fair and ethical and utilise selection tools that select appropriate students. The interview is an integral part of UK dental schools student selection procedures. OBJECTIVE: This study was undertaken in order to determine whether different interview methods (Cardiff with a multiple mini interview and Newcastle with a more traditional interview process) along with other components used in selection predicted academic performance in students. METHODS: The admissions selection data for two dental schools (Cardiff and Newcastle) were collected and analysed alongside student performance in academic examinations in Year 1 of the respective schools. Correlation statistics were used to determine whether selection tools had any relevance to academic performance once students were admitted to their respective Universities. RESULTS: Data was available for a total of 177 students (77 Cardiff and 100 Newcastle). Examination performance did not correlate with admission interview scores at either school; however UKCAT score was linked to poor academic performance. DISCUSSION: Although interview methodology does not appear to correlate with academic performance it remains an integral and very necessary part of the admissions process. Ultimately schools need to be comfortable with their admissions procedures in attracting and selecting the calibre of students they desire. PMID- 26901810 TI - Battle of the sex steroids in the male skeleton: and the winner is.... AB - Male osteoporosis is a multifactorial disease, although it is often in part related to hypogonadism. While testosterone replacement therapy has been shown to improve bone mineral density, studies have also linked bone loss and higher fracture risk in men to low estrogen levels. In this issue of the JCI, Finkelstein and colleagues report the results of a clinical study in a cohort of healthy adult men aimed at further discerning the specific roles of androgen and estrogen deficiency in bone loss. The results of their study support previous findings that estrogen deficiency has a dramatic effect on bone homeostasis in men. Future studies to corroborate and expand on these findings have potential to influence the clinical management of male osteoporosis. PMID- 26901811 TI - In situ analysis of intrahepatic virological events in chronic hepatitis B virus infection. AB - Persistent hepatitis B virus (HBV) infection is established by the formation of an intranuclear pool of covalently closed circular DNA (cccDNA) in the liver. Very little is known about the intrahepatic distribution of HBV cccDNA in infected patients, particularly at the single-cell level. Here, we established a highly sensitive and specific ISH assay for the detection of HBV RNA, DNA, and cccDNA. The specificity of our cccDNA probe set was confirmed by its strict intranuclear signal and by a series of Southern blot analyses. Use of our in situ assay in conjunction with IHC or immunofluorescence uncovered a surprisingly mosaic distribution of viral antigens and nucleic acids. Most strikingly, a mutually exclusive pattern was found between HBV surface antigen-positive (HBsA positive) and HBV DNA- and cccDNA-positive cells. A longitudinal observation of patients over a 1-year period of adeforvir therapy confirmed the persistence of a nuclear reservoir of viral DNA, although cytoplasmic DNA was effectively depleted in these individuals. In conclusion, our method for detecting viral nucleic acids, including cccDNA, with single-cell resolution provides a means for monitoring intrahepatic virological events in chronic HBV infection. More important, our observations unravel the complexity of the HBV life cycle in vivo. PMID- 26901812 TI - Gonadal steroid-dependent effects on bone turnover and bone mineral density in men. AB - BACKGROUND: Severe gonadal steroid deficiency induces bone loss in adult men; however, the specific roles of androgen and estrogen deficiency in hypogonadal bone loss are unclear. Additionally, the threshold levels of testosterone and estradiol that initiate bone loss are uncertain. METHODS: One hundred ninety eight healthy men, ages 20-50, received goserelin acetate, which suppresses endogenous gonadal steroid production, and were randomized to treatment with 0, 1.25, 2.5, 5, or 10 grams of testosterone gel daily for 16 weeks. An additional cohort of 202 men was randomized to receive these treatments plus anastrozole, which suppresses conversion of androgens to estrogens. Thirty-seven men served as controls and received placebos for goserelin and testosterone. Changes in bone turnover markers, bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA), and BMD by quantitative computed tomography (QCT) were assessed in all men. Bone microarchitecture was assessed in 100 men. RESULTS: As testosterone dosage decreased, the percent change in C-telopeptide increased. These increases were considerably greater when aromatization of testosterone to estradiol was also suppressed, suggesting effects of both testosterone and estradiol deficiency. Decreases in DXA BMD were observed when aromatization was suppressed but were modest in most groups. QCT spine BMD fell substantially in all testosterone-dose groups in which aromatization was also suppressed, and this decline was independent of testosterone dose. Estradiol deficiency disrupted cortical microarchitecture at peripheral sites. Estradiol levels above 10 pg/ml and testosterone levels above 200 ng/dl were generally sufficient to prevent increases in bone resorption and decreases in BMD in men. CONCLUSIONS: Estrogens primarily regulate bone homeostasis in adult men, and testosterone and estradiol levels must decline substantially to impact the skeleton. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00114114. FUNDING: AbbVie Inc., AstraZeneca Pharmaceuticals LP, NIH. PMID- 26901813 TI - Lymphatic endothelial cells are a replicative niche for Mycobacterium tuberculosis. AB - In extrapulmonary tuberculosis, the most common site of infection is within the lymphatic system, and there is growing recognition that lymphatic endothelial cells (LECs) are involved in immune function. Here, we identified LECs, which line the lymphatic vessels, as a niche for Mycobacterium tuberculosis in the lymph nodes of patients with tuberculosis. In cultured primary human LECs (hLECs), we determined that M. tuberculosis replicates both in the cytosol and within autophagosomes, but the bacteria failed to replicate when the virulence locus RD1 was deleted. Activation by IFN-gamma induced a cell-autonomous response in hLECs via autophagy and NO production that restricted M. tuberculosis growth. Thus, depending on the activation status of LECs, autophagy can both promote and restrict replication. Together, these findings reveal a previously unrecognized role for hLECs and autophagy in tuberculosis pathogenesis and suggest that hLECs are a potential niche for M. tuberculosis that allows establishment of persistent infection in lymph nodes. PMID- 26901814 TI - Neonatal thymectomy reveals differentiation and plasticity within human naive T cells. AB - The generation of naive T cells is dependent on thymic output, but in adults, the naive T cell pool is primarily maintained by peripheral proliferation. Naive T cells have long been regarded as relatively quiescent cells; however, it was recently shown that IL-8 production is a signatory effector function of naive T cells, at least in newborns. How this functional signature relates to naive T cell dynamics and aging is unknown. Using a cohort of children and adolescents who underwent neonatal thymectomy, we demonstrate that the naive CD4+ T cell compartment in healthy humans is functionally heterogeneous and that this functional diversity is lost after neonatal thymectomy. Thymic tissue regeneration later in life resulted in functional restoration of the naive T cell compartment, implicating the thymus as having functional regenerative capacity. Together, these data shed further light on functional differentiation within the naive T cell compartment and the importance of the thymus in human naive T cell homeostasis and premature aging. In addition, these results affect and alter our current understanding on the identification of truly naive T cells and recent thymic emigrants. PMID- 26901815 TI - New perspectives on the hepatitis B virus life cycle in the human liver. AB - The central role of the transcriptional template of the hepatitis B virus (HBV), covalently closed circular DNA (cccDNA), has been difficult to study in patients with chronic hepatitis B (CHB) infection. In this issue of the JCI, Zhang and colleagues reveal a mosaic distribution of viral antigens and nucleic acids and a mismatch between HBV cccDNA, RNA, and expression of the hepatitis B surface antigen (HBsAg). These unusual patterns varied over the natural history of CHB, prompting the authors to propose a new three-stage model of the HBV life cycle at the single-cell level. PMID- 26901817 TI - Xenotropic retrovirus Bxv1 in human pancreatic beta cell lines. AB - It has been reported that endogenous retroviruses can contaminate human cell lines that have been passaged as xenotransplants in immunocompromised mice. We previously developed and described 2 human pancreatic beta cell lines (EndoC betaH1 and EndoC-betaH2) that were generated in this way. Here, we have shown that B10 xenotropic virus 1 (Bxv1), a xenotropic endogenous murine leukemia virus (MuLV), is present in these 2 recently described cell lines. We determined that Bxv1 was also present in SCID mice that were used for in vivo propagation of EndoC-betaH1/2 cells, suggesting that contamination occurred during xenotransplantation. EndoC-betaH1/2 cells released Bxv1 particles that propagated to human 293T and Mus dunni cells. Mobilization assays demonstrated that Bxv1 transcomplements defective MuLV-based retrovectors. In contrast, common rodent beta cell lines, rat INS-1E and RIN-5F cells and mouse MIN6 and betaTC3 cells, displayed either no or extremely weak xenotropic helper activity toward MuLV based retrovectors, although xenotropic retrovirus sequences and transcripts were detected in both mouse cell lines. Bxv1 propagation from EndoC-betaH1/2 to 293T cells occurred only under optimized conditions and was overall poorly efficient. Thus, although our data imply that MuLV-based retrovectors should be cautiously used in EndoC-betaH1/2 cells, our results indicate that an involuntary propagation of Bxv1 from these cells can be easily avoided with good laboratory practices. PMID- 26901816 TI - A role for genetic susceptibility in sporadic focal segmental glomerulosclerosis. AB - Focal segmental glomerulosclerosis (FSGS) is a syndrome that involves kidney podocyte dysfunction and causes chronic kidney disease. Multiple factors including chemical toxicity, inflammation, and infection underlie FSGS; however, highly penetrant disease genes have been identified in a small fraction of patients with a family history of FSGS. Variants of apolipoprotein L1 (APOL1) have been linked to FSGS in African Americans with HIV or hypertension, supporting the proposal that genetic factors enhance FSGS susceptibility. Here, we used sequencing to investigate whether genetics plays a role in the majority of FSGS cases that are identified as primary or sporadic FSGS and have no known cause. Given the limited number of biopsy-proven cases with ethnically matched controls, we devised an analytic strategy to identify and rank potential candidate genes and used an animal model for validation. Nine candidate FSGS susceptibility genes were identified in our patient cohort, and three were validated using a high-throughput mouse method that we developed. Specifically, we introduced a podocyte-specific, doxycycline-inducible transactivator into a murine embryonic stem cell line with an FSGS-susceptible genetic background that allows shRNA-mediated targeting of candidate genes in the adult kidney. Our analysis supports a broader role for genetic susceptibility of both sporadic and familial cases of FSGS and provides a tool to rapidly evaluate candidate FSGS associated genes. PMID- 26901818 TI - Perseveration induces dissociative uncertainty in obsessive-compulsive disorder. AB - BACKGROUND AND OBJECTIVES: Obsessive compulsive (OC)-like perseveration paradoxically increases feelings of uncertainty. We studied whether the underlying mechanism between perseveration and uncertainty is a reduced accessibility of meaning ('semantic satiation'). METHODS: OCD patients (n = 24) and matched non-clinical controls (n = 24) repeated words 2 (non-perseveration) or 20 times (perseveration). They decided whether this word was related to another target word. Speed of relatedness judgments and feelings of dissociative uncertainty were measured. The effects of real-life perseveration on dissociative uncertainty were tested in a smaller subsample of the OCD group (n = 9). RESULTS: Speed of relatedness judgments was not affected by perseveration. However, both groups reported more dissociative uncertainty after perseveration compared to non perseveration, which was higher in OCD patients. Patients reported more dissociative uncertainty after 'clinical' perseveration compared to non perseveration.. LIMITATIONS: Both parts of this study are limited by some methodological issues and a small sample size. CONCLUSIONS: Although the mechanism behind 'perseveration -> uncertainty' is still unclear, results suggest that the effects of perseveration are counterproductive. PMID- 26901820 TI - Patterns of finasteride use in the male populations of four Nordic countries: A cross-national drug utilization study. AB - Objective Finasteride 5 mg is a drug used to treat prostate hyperplasia. Little is known about its pattern of usage. This cross-national analysis of individual level data from Denmark, Finland, Norway and Sweden was undertaken to appraise its usage and describe cross-national differences. Materials and methods Individual-level data from nationwide prescription registers in Denmark (1995 2009), Finland (1997-2010), Norway (2004-2009) and Sweden (July 2005-2011) were used to examine cross-national finasteride utilization patterns in the adult male population (>=15 years). The study presents period prevalences, incidence rates, waiting time distributions and Lorenz curves. Results During the study period, 295,620 men had at least one prescription redemption of finasteride 5 mg, and there were approximately 3 million dispensing events of finasteride prescriptions in the four Nordic countries. Different patterns of finasteride use were observed among the four Nordic countries. The period prevalence was markedly higher in Finland and Sweden than in Denmark and Norway. In 2009, period prevalences were 18.2/1000 males in Finland and 12.0/1000 males in Sweden compared to 6.7/1000 males in Norway and 4.9/1000 males in Denmark. Incidence rates of finasteride use for Finland, Norway and Sweden were about three times that for Denmark in 2008 2009. Long-term use of finasteride was found in all four Nordic countries with a high ratio between prevalent and incident users. Conclusion Despite resemblances regarding political systems and healthcare services in the Nordic countries, differences in finasteride utilization were found across Denmark, Finland, Norway and Sweden. PMID- 26901819 TI - Analysis of chromatin structure in mouse preimplantation embryos by fluorescent recovery after photobleaching. AB - Zygotes are totipotent cells that have the ability to differentiate into all cell types. It is believed that this ability is lost gradually and differentiation occurs along with the progression of preimplantation development. Here, we hypothesized that the loose chromatin structure is involved in the totipotency of one-cell stage embryos and that the change from loose to tight chromatin structure is associated with the loss of totipotency. To address this hypothesis, we investigated the mobility of eGFP-tagged histone H2B (eGFP-H2B), which is an index for the looseness of chromatin, during preimplantation development based on fluorescent recovery after photobleaching (FRAP) analysis. The highest mobility of eGFP-H2B was observed in pronuclei in 1-cell stage embryos and mobility gradually decreased during preimplantation development. The decrease in mobility between the 1- and 2-cell stages depended on DNA synthesis in 2-cell stage embryos. In nuclear transferred embryos, chromatin in the pseudopronuclei loosened to a level comparable to the pronuclei in 1-cell stage embryos. These results indicated that the mobility of eGFP-H2B is negatively correlated with the degree of differentiation of preimplantation embryos. Therefore, we suggest that highly loosened chromatin is involved in totipotency of 1-cell embryos and the loss of looseness is associated with differentiation during preimplantation development. PMID- 26901821 TI - Recent Development of Advanced Materials with Special Wettability for Selective Oil/Water Separation. AB - The increasing number of oil spill accidents have a catastrophic impact on our aquatic environment. Recently, special wettable materials used for the oil/water separation have received significant research attention. Due to their opposing affinities towards water and oil, i.e., hydrophobic and oleophilic, or hydrophilic and oleophobic, such materials can be used to remove only one phase from the oil/water mixture, and simultaneously repel the other phase, thus achieving selective oil/water separation. Moreover, the synergistic effect between the surface chemistry and surface architecture can further promote the superwetting behavior, resulting in the improved separation efficiency. Here, recently developed materials with special wettability for selective oil/water separation are summarized and discussed. These materials can be categorized based on their oil/water separating mechanisms, i.e., filtration and absorption. In each section, representative studies will be highlighted, with emphasis on the materials wetting properties and innovative aspects. Finally, challenges and future research directions in this emerging and promising research field will be briefly described. PMID- 26901823 TI - Antibiofouling Properties of Plasma-Deposited Oxazoline-Based Thin Films. AB - Infections caused by the bacterial colonization of medical devices are a substantial problem to patients and healthcare. Biopassive polyoxazoline coatings are attracting attention in the biomedical field as one of the potential solutions to this problem. Here, we present an original and swift way to produce plasma-deposited oxazoline-based films for antifouling applications. The films developed via the plasma deposition of 2-methyl-2-oxazoline and 2-ethyl-2 oxazoline have tunable thickness and surface properties. Diverse film chemistries were achieved by tuning and optimizing the deposition conditions. Human-derived fibroblasts were used to confirm the biocompatibility of oxazoline derived coatings. The capacity of the coatings to resist biofilm attachment was studied as a function of deposition power and mode (i.e., continuous wave or pulsed) and precursor flow rates for both 2-methyl-2-oxazoline and 2-ethyl-2-oxazoline. After careful tuning of the deposition parameters films having the capacity to resist biofilm formation by more than 90% were achieved. The substrate-independent and customizable properties of the new generation of plasma deposited oxazoline thin films developed in this work make them attractive candidates for the coating of medical devices and other applications where bacteria surface colonization and biofilm formation is an issue. PMID- 26901822 TI - Comparative Analysis of the Effects of Neurotrophic Factors CDNF and GDNF in a Nonhuman Primate Model of Parkinson's Disease. AB - Cerebral dopamine neurotrophic factor (CDNF) belongs to a newly discovered family of evolutionarily conserved neurotrophic factors. We demonstrate for the first time a therapeutic effect of CDNF in a unilateral 6-hydroxydopamine (6-OHDA) lesion model of Parkinson's disease in marmoset monkeys. Furthermore, we tested the impact of high chronic doses of human recombinant CDNF on unlesioned monkeys and analyzed the amino acid sequence of marmoset CDNF. The severity of 6-OHDA lesions and treatment effects were monitored in vivo using 123I-FP-CIT (DaTSCAN) SPECT. Quantitative analysis of 123I-FP-CIT SPECT showed a significant increase of dopamine transporter binding activity in lesioned animals treated with CDNF. Glial cell line-derived neurotrophic factor (GDNF), a well-characterized and potent neurotrophic factor for dopamine neurons, served as a control in a parallel comparison with CDNF. By contrast with CDNF, only single animals responded to the treatment with GDNF, but no statistical difference was observed in the GDNF group. However, increased numbers of tyrosine hydroxylase immunoreactive neurons, observed within the lesioned caudate nucleus of GDNF treated animals, indicate a strong bioactive potential of GDNF. PMID- 26901824 TI - The contribution of SIPA1 and RRP1B germline polymorphisms to breast cancer phenotype, lymph node status and survival in a group of Lithuanian young breast cancer patients. AB - The germline polymorphisms in signal-inducing proliferation-associated protein 1 (SIPA1) and ribosomal RNR processing 1B (RRP1B) might be involved in breast cancer metastasis. The aim of this study was to analyze how SIPA1 and RRP1B polymorphisms contribute to breast cancer phenotype, lymph node status and survival. A group of 100 young, I-II stage breast cancer patients were analyzed for SIPA1 and RRP1B polymorphisms with PCR-RFLP assay. SIPA1 c.2760G > A, c.545C > T and RRP1B c.436T > C polymorphisms were associated with lymph node status, survival and tumor grade, respectively. Our results suggest that SIPA1 and RRP1B germline polymorphisms are important for breast cancer prognosis. PMID- 26901825 TI - Letter to the Editor. PMID- 26901826 TI - Fenestrated sheet split-thickness skin grafting for reconstruction of penile skin loss in pediatric population. AB - OBJECTIVES: We aimed to evaluate our experience with fenestrated sheet split thickness skin grafts (STSGs) in the pediatric population. MATERIALS AND METHODS: We retrospectively studied a cohort of 17 children 2-18years old who underwent skin grafting owing to circumcision injuries (2 patients), traumatic penile injury (1) and after previous multiple hypospadias surgery (14). Fenestrated 0.012in sheet STSGs from thigh area (15 patients) and buttock area (2) were fashioned to resurface the denuded penis following reconstruction. The median follow up was 13years (range 1-19years). RESULTS: There was 94% take of the grafts. One patient required additional grafting following first graft infection. Six patients underwent concomitant surgery at the time of grafting (4 chordee repair and 2 meatoplasty). Two patients had slight chordee at 3 and 6years postoperatively, and 2 with the history of preputial tubularized island flap hypospadias repair had developed a urethral stricture, which required staged repair with buccal mucosa 12 and 14years following primary hypospadias repair. Six sexually active patients reported normal sexual intercourse and sensation following grafting. None of the patients demonstrated shrinkage of the STSGs over the follow up period. CONCLUSIONS: Our data demonstrated that the use of fenestrated sheet STSGs in patients with penile skin loss yields satisfactory functional and cosmetic outcomes. The buttocks might be considered as a preferable donor site in terms of avoiding a visible scar. PMID- 26901827 TI - A Global Meta-Analysis on the Impact of Management Practices on Net Global Warming Potential and Greenhouse Gas Intensity from Cropland Soils. AB - Management practices, such as tillage, crop rotation, and N fertilization, may affect net global warming potential (GWP) and greenhouse gas intensity (GHGI), but their global impact on cropland soils under different soil and climatic conditions need further evaluation. Available global data from 57 experiments and 225 treatments were evaluated for individual and combined effects of tillage, cropping systems, and N fertilization rates on GWP and GHGI which accounted for CO2 equivalents from N2O and CH4 emissions with or without equivalents from soil C sequestration rate (DeltaSOC), farm operations, and N fertilization. The GWP and GHGI were 66 to 71% lower with no-till than conventional till and 168 to 215% lower with perennial than annual cropping systems, but 41 to 46% greater with crop rotation than monocroppping. With no-till vs. conventional till, GWP and GHGI were 2.6- to 7.4-fold lower when partial than full accounting of all sources and sinks of greenhouse gases (GHGs) were considered. With 100 kg N ha-1, GWP and GHGI were 3.2 to 11.4 times greater with partial than full accounting. Both GWP and GHGI increased curvilinearly with increased N fertilization rate. Net GWP and GHGI were 70 to 87% lower in the improved combined management that included no till, crop rotation/perennial crop, and reduced N rate than the traditional combined management that included conventional till, monocopping/annual crop, and recommended N rate. An alternative soil respiration method, which replaces DeltaSOC by soil respiration and crop residue returned to soil in the previous year, similarly reduced GWP and GHGI by 133 to 158% in the improved vs. the traditional combined management. Changes in GWP and GHGI due to improved vs. traditional management varied with the duration of the experiment and inclusion of soil and climatic factors in multiple linear regressions improved their relationships. Improved management practices reduced GWP and GHGI compared with traditional management practices and combined management practices were even more effective than individual management practices in reducing net GHG emissions from cropland soils. Partial accounting overestimated GWP and GHGI values as sinks or sources of net GHGs compared with full accounting when evaluating the effect of management practices. PMID- 26901830 TI - Developments in precision medicine: Studies highlight new applications for cancer chemoprevention, treatment. PMID- 26901828 TI - A Comparison between BMI, Waist Circumference, and Waist-To-Height Ratio for Identifying Cardio-Metabolic Risk in Children and Adolescents. AB - BACKGROUND: There is controversial evidence on the associations between anthropometric measures with clustering of cardiovascular disease risk factors in pediatric ages. We aimed to examine the associations between body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) with clustered cardiometabolic risk factors and to determine whether these anthropometric variables can be used to discriminate individuals with increased cardiometabolic risk (increased clustered triglycerides, HDL-cholesterol, systolic and diastolic blood pressure, and HOMA-IR). METHODS: The study sample of 4255 (2191 girls and 2064 boys) participants (8-17 years) was derived from pooled cross-sectional data comprising five studies. Outcomes included a continuous cardiometabolic risk factor z-score [corresponding to the sum of z-scores for triglycerides, HDL cholesterol, systolic and diastolic blood pressure (mean arterial pressure), and HOMA-IR] and children with >=1.0 SD in this score were defined as being at risk for clustering cardiometabolic risk factors.. Exposure variables were BMI, WC, WHtR. Statistics included mixed-effect regression and ROC analysis. RESULTS: All anthropometric variables were associated with clustered risk and the magnitudes of associations were similar for BMI, WC, and WHtR. Models including anthropometric variables were similar in discriminating children and adolescents at increased risk with areas under the ROC curve between 0.70 and 0.74. The sensitivity (boys: 80.5-86.4%; girls: 76.6-82.3%) was markedly higher than specificity (boys: 51.85-59.4%; girls: 60.8%). CONCLUSIONS: The magnitude of associations for BMI, WC, and WHtR are similar in relation to clustered cardiometabolic risk factors, and perform better at higher levels of BMI. However, the precision of these anthropometric variables to classify increased risk is low. PMID- 26901831 TI - Older tobacco users pay more under the Affordable Care Act. PMID- 26901829 TI - BDNF Val66Met Polymorphism Is Associated with Self-Reported Empathy. AB - Empathy is an important driver of human social behaviors and presents genetic roots that have been studied in neuroimaging using the intermediate phenotype approach. Notably, the Val66Met polymorphism of the Brain-derived neurotrophic factor (BDNF) gene has been identified as a potential target in neuroimaging studies based on its influence on emotion perception and social cognition, but its impact on self-reported empathy has never been documented. Using a neurogenetic approach, we investigated the association between the BDNF Val66Met polymorphism and self-reported empathy (Davis' Interpersonal Reactivity Index; IRI) in a sample of 110 young adults. Our results indicate that the BDNF genotype is significantly associated with the linear combination of the four facets of the IRI, one of the most widely used self-reported empathy questionnaire. Crucially, the effect of BDNF Val66Met goes beyond the variance explained by two polymorphisms of the oxytocin transporter gene previously associated with empathy and its neural underpinnings (OXTR rs53576 and rs2254298). These results represent the first evidence suggesting a link between the BDNF gene and self reported empathy and warrant further studies of this polymorphism due to its potential clinical significance. PMID- 26901832 TI - ACS updates breast cancer screening guidelines. PMID- 26901833 TI - Pollack CE, Soulos PR and Gross CP. Physician's peer exposure and the adoption of a new cancer treatment modality. Cancer. 2015;121:2799-2807. PMID- 26901834 TI - Conservative Tests under Satisficing Models of Publication Bias. AB - Publication bias leads consumers of research to observe a selected sample of statistical estimates calculated by producers of research. We calculate critical values for statistical significance that could help to adjust after the fact for the distortions created by this selection effect, assuming that the only source of publication bias is file drawer bias. These adjusted critical values are easy to calculate and differ from unadjusted critical values by approximately 50% rather than rejecting a null hypothesis when the t-ratio exceeds 2, the analysis suggests rejecting a null hypothesis when the t-ratio exceeds 3. Samples of published social science research indicate that on average, across research fields, approximately 30% of published t-statistics fall between the standard and adjusted cutoffs. PMID- 26901835 TI - Adapting coculture in vitro models of the blood-brain barrier for use in cancer research: maintaining an appropriate endothelial monolayer for the assessment of transendothelial migration. AB - Although brain metastases are the most common brain tumors in adults, there are few treatment options in this setting. To colonize the brain, circulating tumor cells must cross the blood-brain barrier (BBB), which is situated within specialized, restrictive microvascular endothelium. Understanding how cancer cells manage to transmigrate through the BBB might enable this process to be prevented. In vitro models are dedicated tools for characterizing the cellular and molecular mechanisms that underlie transendothelial migration process, as long as they accurately mimic the brain endothelium's in vivo characteristics. The objective of the present study was to adapt an existing in vitro model of the human BBB for use in studying cancer cell transmigration. The model is based on the coculture of endothelial cells (ECs, derived from cord blood hematopoietic stem cells) and brain pericytes. To allow the migration of cancer cells into the lower compartment, our model had to be transposed onto inserts with a larger pore size. However, we encountered a problem when culturing ECs on large (3-MUm)-pore inserts: the cells crossed the membrane and formed a non-physiological second layer on the lower face of the insert. Using 3-MUm-pore inserts (in a 12-well plate format), we report here on a method that enables the maintenance of a single monolayer of ECs on the insert's upper face only. Under these chosen conditions, the ECs exhibited typical BBB properties found in the original model (including restricted paracellular permeability and the expression of continuous tight junctions). This modified in vitro model of the human BBB enabled us to investigate the migratory potential of the MDA-MB-231 cell line (derived from highly metastatic human breast cancer cells). Last, the results obtained were compared with the rate of transmigration through endothelia with no BBB features. PMID- 26901836 TI - PHD/HIF-1 upregulates CA12 to protect against degenerative disc disease: a human sample, in vitro and ex vivo study. AB - Intervertebral disc degeneration is a major cause of low back pain. The nucleus pulposus (NP) is an important intervertebral disc component. Recent studies have shown that carbonic anhydrase 12 (CA12) is a novel NP marker. However, the mechanism by which CA12 is regulated and its physiological function are unclear. In our study, CA12, hypoxia-inducible factor 1alpha (HIF-1alpha) and HIF-2alpha expression levels were examined in 81 human degenerated NP samples using real time RT-PCR, immunohistochemistry and western blot. Rat NP cells were cultured in a hypoxic environment, and hypoxia-induced CA12 expression was examined. Rat NP cells were treated with HIF-1alpha siRNA or the prolyl hydroxylase (PHD) inhibitor dimethyloxalylglycine (DMOG) to evaluate the role of PHD/HIF-1 in regulating CA12 expression. Rat NP cells were treated with CA12 siRNA to determine the function of CA12. A rat ex vivo model was established to confirm that PHD, HIF-1, and CA12 have important roles in disc degeneration. We found that CA12 was significantly downregulated in degenerated human NP samples at the mRNA and protein levels. CA12 expression sharply increased by ~30-fold in response to hypoxia. The expression of HIF-1alpha, but not HIF-2alpha, also decreased in degenerated human NP samples and was positively correlated with CA12 expression. HIF-1alpha knockdown under hypoxia reduced the CA12 mRNA and protein expression levels. DMOG treatment increased HIF-1alpha and CA12 expression. CA12 knockdown significantly inhibited anabolic protein expression, whereas catabolic enzymes remained unchanged. The ex vivo experiments supported our in vitro studies of the role of PHD/HIF-1/CA12. In conclusion, CA12 is downregulated in degenerated NPs, and its expression may be regulated by the PHD/HIF-1 axis. Decreased CA12 expression may lead to decreased extracellular matrix synthesis, which contributes to degenerative disc disease progression. PMID- 26901837 TI - Quantitative determination of the surfactant-induced split ratio of influenza virus by fluorescence spectroscopy. AB - The majority of marketed seasonal influenza vaccines are prepared using viruses that are chemically inactivated and treated with a surfactant. Treating with surfactants has important consequences: it produces 'split viruses' by solubilizing viral membranes, stabilizes free membrane proteins and ensures a low level of reactogenicity while retaining high vaccine potency. The formulation stability and potency of split influenza vaccines are largely determined by the specifics of this 'splitting' process; namely, the consequent conformational changes of proteins and interactions of solubilized particles, which may form aggregates. Robust methods to quantitatively determine the split ratio need to be developed before optimal splitting conditions can be investigated to streamline production of superior influenza vaccines. Here, we present a quantitative method, based on both steady-state and time-resolved fluorescence spectroscopy, to calculate the split ratio of the virus after surfactant treatment. We use the lipophilic dye Nile Red (NR) as a probe to elucidate molecular interactions and track changes in molecular environments. Inactivated whole influenza viruses obtained from a sucrose gradient were incubated with NR and subsequently treated with increasing concentrations of the surfactant Triton X-100 (TX-100) to induce virus splitting. NR's emission spectra showed that the addition of TX-100 caused ~27 nm red-shifts in the emission peak, indicative of increasingly hydrophilic environments surrounding NR. The emission spectra of NR at different surfactant concentrations were analyzed with multi-peak fitting to ascertain the number of different micro-environments surrounding NR and track its population change in these different environments. Results from both the emission spectra and fluorescence lifetime spectroscopy revealed that NR showed presence in 3 distinct molecular environments. The split ratio of the virus was then calculated from the percentages of NR in these environments using both fluorescence emission and lifetime data. This study can pave the way for the development of robust methods to rapidly quantify splitting extent during vaccine manufacturing. PMID- 26901838 TI - The Dietary Isoflavone Daidzein Reduces Expression of Pro-Inflammatory Genes through PPARalpha/gamma and JNK Pathways in Adipocyte and Macrophage Co-Cultures. AB - Obesity-induced inflammation caused by adipocyte-macrophage interactions plays a critical role in developing insulin resistance, and peroxisome proliferator activated receptors (PPARs) regulate inflammatory gene expression in these cells. Recently, the soy isoflavone daidzein was reported to act as a PPAR activator. We examined whether daidzein affected adipocyte-macrophage crosstalk via the regulation of PPARs. Co-cultures of 3T3-L1 adipocytes and RAW264 macrophages, or palmitate-stimulated RAW264 macrophages were treated with daidzein in the presence or absence of specific inhibitors for PPARs: GW6471 (a PPARalpha antagonist), and GW9662 (a PPARgamma antagonist). Inflammatory gene expression was then determined. Daidzein significantly decreased chemokine (C-C motif) ligand 2 (Ccl2, known in humans as monocyte chemo-attractant protein 1 (MCP1)) and interleukin 6 (Il6) mRNA levels induced by co-culture. In 3T3-L1 adipocytes, daidzein inversed the attenuation of adiponectin gene expression by co-culture, and these effects were inhibited by the PPAR-gamma specific inhibitor. Daidzein also decreased Ccl2 and Il6 mRNA levels in RAW264 macrophages stimulated with palmitate or conditioned medium (CM) from hypertrophied 3T3-L1 adipocytes. This inhibitory effect on Il6 expression was abrogated by a PPAR-alpha inhibitor. Additionally, we examined the activation of nuclear factor-kappa B (NF-kappaB) and c-Jun N-terminal kinase (JNK) pathways and found that daidzein significantly inhibited palmitate-induced phosphorylation of JNK. Our data suggest that daidzein regulates pro-inflammatory gene expression by activating PPAR-alpha and gamma and inhibiting the JNK pathway in adipocyte and macrophage co-cultures. These effects might be favorable in improving adipose inflammation, thus, treatment of daidzein may be a therapeutic strategy for chronic inflammation in obese adipose tissue. PMID- 26901839 TI - Long-term Surveillance of Physical Activity Habits of Latinas Enrolled in a 12 Month Physical Activity Intervention. AB - BACKGROUND: Long-term physical activity surveillance has not been conducted among Latinas. This study explored the variability of daily physical activity habits of inactive adult Latinas participating in a 12-month physical activity intervention. METHODS: We collected objective physical activity data (pedometer) from 139 Spanish speaking Latinas (age = 41.6 +/- 10.1 years; BMI = 29.6 +/- 4.3 kg/m2) enrolled in a 12-month physical activity intervention. Total and aerobic steps (>100 steps/minute) were computed by year, season, month, day of week, time of day, and hour. RESULTS: Participants walked an average of 6509 steps/day of which 1303 (20%) were aerobic steps. Significant physical activity differences were observed for subgroups including generational status, education, employment, income, marital status and health literacy. Significant and similar differences were observed for both total steps and aerobic steps for day of the week (weekdays > weekends) and season (summer > spring > fall > winter). Opposing trends were observed over the course of the day for total steps (early afternoon > late morning > late afternoon > early morning > evening) and aerobic steps (early morning > evening > late morning > late afternoon > early afternoon). CONCLUSIONS: Both seasonality and week day predicted physical activity habits of Latinas. This is the first long-term study to track daily physical activity habits of Latinas. These data have potential to inform the design of future physical activity interventions targeting Latinas. PMID- 26901840 TI - Single-scan MRI with exceptional resilience to field heterogeneities. AB - PURPOSE: Single-scan two-dimensional MRI has been generally constrained to acquisitions in high quality magnets. This study introduces a methodology, cross term spatiotemporal encoding (xSPEN), that delivers such images under much poorer external field conditions. METHODS: xSPEN departs from conventional k-space scanning, by relying on spatiotemporally encoding the image being sought. Unlike hitherto proposed SPEN methods, however, xSPEN's image readout does not take place using a field gradient along the direction being probed, but rather with the aid of an ancillary source of inhomogeneous frequency broadening. This ancillary dimension was here imposed by an orthogonal field gradient; for example, images along the "y" axis were read out by application of a "z" gradient. The principles and characteristics of this new approach, compatible with existing scanners and free from the need to collect auxiliary information such as field maps, are presented and discussed. RESULTS: Single- and multi-slice in vitro, ex vivo, and in vivo MRI experiments, confirmed the unusual resilience of this new single-shot MRI method to multiple chemical sites on phantoms, animals and humans. CONCLUSION: xSPEN can deliver single-scan MRI with good sensitivity and exceptional resilience to field inhomogeneities. This could enable investigations that have hitherto escaped from MRI's scope. Magn Reson Med 77:623-634, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 26901841 TI - Anti-Pseudomonas aeruginosa IgY antibodies promote bacterial opsonization and augment the phagocytic activity of polymorphonuclear neutrophils. AB - Moderation of polymorphonuclear neutrophils (PMNs) as part of a critical defense against invading pathogens may offer a promising therapeutic approach to supplement the antibiotic eradication of Pseudomonas aeruginosa infection in non chronically infected cystic fibrosis (CF) patients. We have observed that egg yolk antibodies (IgY) harvested from White leghorn chickens that target P. aeruginosa opsonize the pathogen and enhance the PMN-mediated respiratory burst and subsequent bacterial killing in vitro. The effects on PMN phagocytic activity were observed in different Pseudomonas aeruginosa strains, including clinical isolates from non-chronically infected CF patients. Thus, oral prophylaxis with anti-Pseudomonas aeruginosa IgY may boost the innate immunity against Pseudomonas aeruginosa in the CF setting by facilitating a rapid and prompt bacterial clearance by PMNs. PMID- 26901842 TI - Coupled reactions on bioparticles: Stereoselective reduction with cofactor regeneration on PhaC inclusion bodies. AB - Chiral alcohols are important building blocks for specialty chemicals and pharmaceuticals. The production of chiral alcohols from ketones can be carried out stereo selectively with alcohol dehydrogenases (ADHs). To establish a process for cost-effective enzyme immobilization on solid phase for application in ketone reduction, we used an established enzyme pair consisting of ADH from Rhodococcus erythropolis and formate dehydrogenase (FDH) from Candida boidinii for NADH cofactor regeneration and co-immobilized them on modified poly-p-hydroxybutyrate synthase (PhaC)-inclusion bodies that were recombinantly produced in Escherichia coli cells. After separate production of genetically engineered and recombinantly produced enzymes and particles, cell lysates were combined and enzymes endowed with a Kcoil were captured on the surface of the Ecoil presenting particles due to coiled-coil interaction. Enzyme-loaded particles could be easily purified by centrifugation. Total conversion of 4'-chloroacetophenone to (S)-4-chloro-alpha methylbenzyl alcohol could be accomplished using enzyme-loaded particles, catalytic amounts of NAD(+) and formate as substrates for FDH. Chiral GC-MS analysis revealed that immobilized ADH retained enantioselectivity with 99 % enantiomeric excess. In conclusion, this strategy may become a cost-effective alternative to coupled reactions using purified enzymes. PMID- 26901843 TI - ANXA5: a key to unlock the mystery of the spectrum of placental-mediated pregnancy complications? PMID- 26901844 TI - Increase in Ticks and Lyme Borreliosis, Yet Research into Its Prevention on the Wane. AB - There is increased concern about the upward incidence of Lyme Borreliosis (LB) in Europe, the United States, Asia, and Northern Africa. However, effective measures to control tick populations or vaccines for LB are not yet available. Therefore, behavioral measures including avoidance of areas inhabited by ticks, performing routine body checks, using protective clothing, and the application of tick repellents are of great importance. Unfortunately, acceptance and uptake of many of these preventive behaviors are currently low. Hence, effective health education and public health communication aimed at promoting the uptake of preventive behaviors regarding tick bites and LB are urgently needed. In 2012, Mowbray recommended to conduct more research aimed at improving evidence-based insights regarding the promotion of preventive behaviors among the general public when exposed to the risk of LB. We fully agree with Mowbray and repeated her systematic review in May 2015 covering the period 1995-May 2015. Unfortunately, our review yielded exactly the same studies as already included in the review by Mowbray. Therefore, we again sound the alarm bell, just as Mowbray did a few years ago. As long as there are no effective measures for controlling tick populations and there is no vaccine available, we rely solely on health education and communication efforts to prevent tick bites and LB. We call on researchers and funders to prioritize research in the field of public health interventions for tick bites and LB because, in the words of Benjamin Franklin, "an ounce of prevention is worth a pound of cure." PMID- 26901845 TI - End to End Digitisation and Analysis of Three-Dimensional Coral Models, from Communities to Corallites. AB - Coral reefs hosts nearly 25% of all marine species and provide food sources for half a billion people worldwide while only a very small percentage have been surveyed. Advances in technology and processing along with affordable underwater cameras and Internet availability gives us the possibility to provide tools and softwares to survey entire coral reefs. Holistic ecological analyses of corals require not only the community view (10s to 100s of meters), but also the single colony analysis as well as corallite identification. As corals are three dimensional, classical approaches to determine percent cover and structural complexity across spatial scales are inefficient, time-consuming and limited to experts. Here we propose an end-to-end approach to estimate these parameters using low-cost equipment (GoPro, Canon) and freeware (123D Catch, Meshmixer and Netfabb), allowing every community to participate in surveys and monitoring of their coral ecosystem. We demonstrate our approach on 9 species of underwater colonies in ranging size and morphology. 3D models of underwater colonies, fresh samples and bleached skeletons with high quality texture mapping and detailed topographic morphology were produced, and Surface Area and Volume measurements (parameters widely used for ecological and coral health studies) were calculated and analysed. Moreover, we integrated collected sample models with micro photogrammetry models of individual corallites to aid identification and colony and polyp scale analysis. PMID- 26901846 TI - Co-sputtered MoRe thin films for carbon nanotube growth-compatible superconducting coplanar resonators. AB - Molybdenum rhenium alloy thin films can exhibit superconductivity up to critical temperatures of T(c)=15K. At the same time, the films are highly stable in the high-temperature methane/hydrogen atmosphere typically required to grow single wall carbon nanotubes. We characterize molybdenum rhenium alloy films deposited via simultaneous sputtering from two sources, with respect to their composition as function of sputter parameters and their electronic dc as well as GHz properties at low temperature. Specific emphasis is placed on the effect of the carbon nanotube growth conditions on the film. Superconducting coplanar waveguide resonators are defined lithographically; we demonstrate that the resonators remain functional when undergoing nanotube growth conditions, and characterize their properties as function of temperature. This paves the way for ultra-clean nanotube devices grown in situ onto superconducting coplanar waveguide circuit elements. PMID- 26901847 TI - Radiotherapy diagnostic biomarkers in radioresistant human H460 lung cancer stem like cells. AB - Tumor cell radioresistance is a major contributor to radiotherapy failure, highlighting the importance of identifying predictive biomarkers for radioresistance. In this work, we established a radioresistant H460 (RR-H460) cell line from parental radiosensitive H460 lung cancer cells by exposure to fractionated radiation. The radiation-resistant, anti-apoptotic phenotype of RR H460 cell lines was confirmed by their enhanced clonogenic survival and increased expression of the radioresistance genes Hsp90 and Her-3. RR-H460 cells displayed characteristics of cancer stem-like cells (CSCs), including induction of the surface marker CD44 and stem cell markers Nanog, Oct4, and Sox2. RR-H460 cells also exhibited sphere formation and malignant behavior, further supporting a CSC phenotype. Using proteomic analyses, we identified 8 proteins that were up regulated in RR-H460 CSC lines and therefore potentially involved in radioresistance and CSC-related biological processes. Notably, 4 of these-PAI-2, NOMO2, KLC4, and PLOD3-have not been previously linked to radioresistance. Depletion of these individual genes sensitized RR-H460 cells to radiotoxicity and additively enhancing radiation-induced apoptosis. Our findings suggest the possibility of integrating molecular targeted therapy with radiotherapy as a strategy for resolving the radioresistance of lung tumors. PMID- 26901848 TI - Prefractionation methods for individual adult fruit fly hemolymph proteomic analysis. AB - The analysis of blood provides in depth chemical information of physiological states of organisms. Hemolymph (blood) is the fluid in the open circulatory system of Drosophila melanogaster that is the medium for molecules regulating a wide variety of physiological activities and signaling between tissues. Adult Drosophila is typically less than 3mm in length and, as a consequence, the available volume of hemolymph is usually less than 50 nL from individual flies. Proteomic analysis of volume-limited hemolymph is a great challenge for both sample handling and subsequent mass spectrometry characterization of this chemically diverse biological fluid with a wide dynamic range of proteins in concentrations. Less abundant proteins, in particular, could be easily lost during sample preparation or missed by current mass spectrometry methods. This article describes simple and customized RPLC column and IEX columns to prefractionate volume-limited hemolymph without excessive dilution. Step-gradient elution methods were developed and optimized to enhance the identification of novel proteins from an individual fruit fly hemolymph sample. Fractions from each step gradient was analyzed by an Agilent nano-RPLC chip column and then characterized by high mass resolution and high mass accuracy orbitrap mass spectrometry. As a result, both RPLC (11 proteins) and IEX fractionation approaches (9 proteins) identified more proteins than an unfractionated control approach with higher protein scores, emPAI values and coverage. Furthermore, a significant number of novel proteins were revealed by both RPLC and IEX fractionation methods, which were missed by unfractionated controls. The demonstration of this method establishes a means to deepen proteomic analysis to this commonly used, important biological model system. PMID- 26901849 TI - Chemometrics applied to quality control and metabolomics for traditional Chinese medicines. AB - Traditional Chinese medicines (TCMs) bring a great challenge in quality control and evaluating the efficacy because of their complexity of chemical composition. Chemometric techniques provide a good opportunity for mining more useful chemical information from TCMs. Then, the application of chemometrics in the field of TCMs is spontaneous and necessary. This review focuses on the recent various important chemometrics tools for chromatographic fingerprinting, including peak alignment information features, baseline correction and applications of chemometrics in metabolomics and modernization of TCMs, including authentication and evaluation of the quality of TCMs, evaluating the efficacy of TCMs and essence of TCM syndrome. In the conclusions, the general trends and some recommendations for improving chromatographic metabolomics data analysis are provided. PMID- 26901850 TI - Enhanced Photoresponse of Conductive Polymer Nanowires Embedded with Au Nanoparticles. AB - A conductive polymer nanowire embedded with a 1D Au nanoparticle chain with defined size, shape, and interparticle distance is fabricated which demonstrates enhanced photoresponse behavior. The precise and controllable positioning of 1D Au nanoparticle chain in the conductive polymer nanowire plays a critical role in modulating the photoresponse behavior by excitation light wavelength or power due to the coupled-plasmon effect of 1D Au nanoparticle chain. PMID- 26901851 TI - Effects of peri-operative bridging with low molecular weight heparins on coagulation during interruption of vitamin K antagonists: A mechanistic study. AB - BACKGROUND: Bridging with low molecular weight heparins (LMWH) is used in patients undergoing invasive procedures that require interruption of vitamin K antagonists (VKA). Little is known on the mechanisms underlying observed thrombotic and bleeding events. In this exploratory study we investigated the interactive effects of the co-administration of VKA, LMWH and surgery on coagulation. MATERIALS AND METHODS: Blood was sampled daily from day -3 to day +5 in 13 patients. In addition to measurement of INR, anti-Xa activity, thrombin generation (TG) testing and assessment of its protein determinants was performed. RESULTS: At the time of intervention the mean INR was 1.0 (SD 0.1, range 0.9 1.2); the mean residual anti-Xa level was 0.19 units/ml (SD 0.20 units/ml, range<0.05-0.60). The intervention caused a 2-3 fold increase in TG at day 0. Factor (F) XI had the strongest correlation with TG (peak and endogenous thrombin potential (ETP)) (r=0.6; p=0.02). Thrombomodulin-induced reduction of ETP increased from 10.0% (SD 9.2) at day -3 to 18.2% (SD 9.5) at day 0, p=0.02. After surgery, FVIII (175.9%(SD 58.9% to 246.7% (SD 71.4%); p=0.002) and fibrinogen (4.3 g/L (SD 1.1 g/L) to 5.6 g/L (SD 1.7 g/L); p=0.003) were significantly increased. CONCLUSIONS: Residual anti-Xa activity was present in 84.6% of patients at the day of the intervention. Three prothrombotic mechanisms were exposed: FXI dependent TG, reduced activity of the activated protein C pathway and postoperative rises in FVIII and fibrinogen. For the perioperative management the value of TG merits further study. PMID- 26901852 TI - Accuracy of point of care coagulometers compared to reference laboratory measurements in patients on oral anticoagulation therapy. AB - BACKGROUND: Vitamin K antagonists (VKA) are widely prescribed throughout the world. Patients on VKA therapy require international normalized ratio (INR) monitoring of venous blood to ensure the response remains within the therapeutic window. Point-of-care devices (POC-INR) can safely and easily monitor VKA efficacy but need to be evaluated in practice. The aim of this study was to assess the precision and accuracy of a new POC-INR (Qlab) compared to the laboratory plasma technique and the CoaguChek-XS system. METHODS: Consecutive patients on VKA referred to our institution were included. The study was designed to analyze 75 patients divided equally in the following subgroups: INR<2; INR=2 3; INR>3. INR was measured with an established laboratory method (INRREF) with an international sensitivity index of 1.0 and by two different POC-INRs: the Qlab (INRQlab) and the CoaguChek-XS systems (INRXS). RESULTS: 82 patients treated mainly for atrial fibrillation or venous thromboembolism disease were included. Precision in therapeutic range (INR=2-3) of both POC-INRs was satisfactory with a coefficient of variation of 4.6% for the Qlab and 4.3% for the CoaguChek-XS. INRRef was 2.70 +/- 1.36, INRQlab 2.59 +/- 1.25 and INRXS 2.89 +/- 1.37. Accuracy was low with the Qlab (R(2)=0.64) and higher with the CoaguChek-XS (R(2)=0.94). The mean relative difference from the INRRef was higher for the Qlab (18.4%) than for the CoaguChek-XS (12.9%). Clinical concordance was lower with the Qlab (78.2%) than with the CoaguChek-XS (90.0%). CONCLUSION: This study suggests that the Qlab has accuracy limitations with clinical consequences. New POC-INR devices require careful evaluation prior to clinical implementation. PMID- 26901853 TI - Efficacy of immunomodulatory therapy with all-trans retinoid acid in adult patients with chronic immune thrombocytopenia. AB - INTRODUCTION: Immune thrombocytopenia (ITP) is a common hematologic disorder characterized by isolated thrombocytopenia. In adults, ITP is more likely to be chronic, requiring individualised treatment and management. Corticosteroids and splenectomy are the most common therapy for ITP. However, these routine approaches failed in these patients with chronic ITP. The aim of this study was to evaluate the efficacy of immunomodulatory therapy with all-trans retinoid acid (ATRA) in adult patients with chronic ITP. MATERIALS AND METHODS: ATRA therapy was applied in a total of 35 patients with chronic ITP who failed with standard dose corticosteroids and/or splenectomy. The response ratio and the change of the T cell subsets including Th1, Th2, Th17 and Treg, were evaluated. RESULTS: Complete response and overall response were observed in 10 (28.6%) and 19 patients (54.3%), respectively. Compared with the control group, a significant decreased level of Treg cells, IL-10 and Foxp3 expression were found in ITP patients. ATRA therapy could significantly increase the percentage of Treg cell, IL-10 level and Foxp3 expression. CONCLUSIONS: Our findings indicate that ATRA therapy could induce significant changes of Treg cells to induce response in patients with chronic ITP. PMID- 26901854 TI - Community Perceptions of Community Health Workers (CHWs) and Their Roles in Management for HIV, Tuberculosis and Hypertension in Western Kenya. AB - Given shortages of health care providers and a rise in the number of people living with both communicable and non-communicable diseases, Community Health Workers (CHWs) are increasingly incorporated into health care programs. We sought to explore community perceptions of CHWs including perceptions of their roles in chronic disease management as part of the Academic Model Providing Access to Healthcare Program (AMPATH) in western Kenya. In depth interviews and focus group discussions were conducted between July 2012 and August 2013. Study participants were purposively sampled from three AMPATH sites: Chulaimbo, Teso and Turbo, and included patients within the AMPATH program receiving HIV, tuberculosis (TB), and hypertension (HTN) care, as well as caregivers of children with HIV, community leaders, and health care workers. Participants were asked to describe their perceptions of AMPATH CHWs, including identifying the various roles they play in engagement in care for chronic diseases including HIV, TB and HTN. Data was coded and various themes were identified. We organized the concepts and themes generated using the Andersen-Newman Framework of Health Services Utilization and considering CHWs as a potential enabling resource. A total of 207 participants including 110 individuals living with HIV (n = 50), TB (n = 39), or HTN (n = 21); 24 caregivers; 10 community leaders; and 34 healthcare providers participated. Participants identified several roles for CHWs including promoting primary care, encouraging testing, providing education and facilitating engagement in care. While various facilitating aspects of CHWs were uncovered, several barriers of CHW care were raised, including issues with training and confidentiality. Suggested resources to help CHWs improve their services were also described. Our findings suggest that CHWs can act as catalysts and role models by empowering members of their communities with increased knowledge and support. PMID- 26901855 TI - Public injury prevention system in the Italian manufacturing sector: What types of inspection are more effective? AB - BACKGROUND: Literature suggests that more research is needed to clarify the effect of workplace inspections by governmental officers on injury rates. This paper aims to compare comprehensive and partial inspections in Italian manufacturing companies. METHODS: Survival analysis was applied to the period free from injuries following inspection by means of the Kaplan-Meier method and of Cox models. RESULTS: Kaplan-Meier curves show that, compared to companies with a partial inspection, companies which had a comprehensive inspection had a higher survival through the entire period. Adjusting for confounders, the Cox model confirms a significant preventive effect of comprehensive inspection for companies with 10-30 employees, but not for those with >30 employees. CONCLUSIONS: The results suggest that the effect on injuries is greater if all aspects of safety are addressed during the inspection instead of focusing on a single aspect. These findings are interesting because they can help in planning effective prevention activities. PMID- 26901856 TI - The Activation of ERK1/2 and JNK MAPK Signaling by Insulin/IGF-1 Is Responsible for the Development of Colon Cancer with Type 2 Diabetes Mellitus. AB - Previous studies showed that type 2 diabetes mellitus (T2DM) is linked to increased risk of developing colon cancer. Insulin and insulin-like growth factor 1 (IGF-1) are increased in patients with T2DM. The increased insulin and IGF-1 may be responsible for the developing of colon cancer. In this study, we investigated the effects and mechanisms of insulin and IGF-1 in colon cancer development in vitro and in vivo. Insulin and IGF-1 alone or together elevated proliferation and reduced apoptosis in colon cancer MC38 cells. Meanwhile, insulin and IGF-1 promoted the phosphorylation of extracellular-signal regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK). Treatment with ERK1/2 or JNK inhibitor in the presence of insulin and IGF-1 significantly decreased B-cell lymphoma 2 (Bcl-2) and increased Bcl-2-associated X protein (Bax) expression and finally increased apoptosis and inhibited the proliferation. Accelerative colon tumor growth was found in a mouse model of T2DM with db/db mice which got high level of endogenous insulin and IGF-1. Furthermore, the inhibition of ERK1/2 or JNK suppressed the development of colon tumor in vivo. These results suggest that the activation of ERK1/2 and JNK signaling by insulin and IGF-1, at least in part, is responsible for the development of colon cancer with T2DM. PMID- 26901857 TI - An Attention-Sensitive Memory Trace in Macaque MT Following Saccadic Eye Movements. AB - We experience a visually stable world despite frequent retinal image displacements induced by eye, head, and body movements. The neural mechanisms underlying this remain unclear. One mechanism that may contribute is transsaccadic remapping, in which the responses of some neurons in various attentional, oculomotor, and visual brain areas appear to anticipate the consequences of saccades. The functional role of transsaccadic remapping is actively debated, and many of its key properties remain unknown. Here, recording from two monkeys trained to make a saccade while directing attention to one of two spatial locations, we show that neurons in the middle temporal area (MT), a key locus in the motion-processing pathway of humans and macaques, show a form of transsaccadic remapping called a memory trace. The memory trace in MT neurons is enhanced by the allocation of top-down spatial attention. Our data provide the first demonstration, to our knowledge, of the influence of top-down attention on the memory trace anywhere in the brain. We find evidence only for a small and transient effect of motion direction on the memory trace (and in only one of two monkeys), arguing against a role for MT in the theoretically critical yet empirically contentious phenomenon of spatiotopic feature-comparison and adaptation transfer across saccades. Our data support the hypothesis that transsaccadic remapping represents the shift of attentional pointers in a retinotopic map, so that relevant locations can be tracked and rapidly processed across saccades. Our results resolve important issues concerning the perisaccadic representation of visual stimuli in the dorsal stream and demonstrate a significant role for top-down attention in modulating this representation. PMID- 26901858 TI - Computing Molecular Devices in L.major through Transcriptome Analysis: Structured Simulation Approach. AB - In the modern era of post genomics and transcriptomics, non-coding RNAs and non coding regions of many RNAs are a big puzzle when we try deciphering their role in specific gene function. Gene function assessment is a main task wherein high throughput technologies provide an impressive body of data that enables the design of hypotheses linking genes to phenotypes. Gene knockdown technologies and RNA-dependent gene silencing are the most frequent approaches to assess the role of key effectors in a particular scenario. Ribozymes are effective modulators of gene expression because of their simple structure, site-specific cleavage activity, and catalytic potential. In our study, after an extensive transcriptomic search of Leishmania major transcriptome we found a Putative ATP dependent DNA helicase (Lmjf_09_0590) 3' UTR which has a structural signature similar to well-known HDV hammerhead ribozyme, even though they have variable sequence motifs. Henceforth, to determine their structural stability and sustainability we analyzed our predicted structural model of this 3'UTR with a 30ns MD simulation, further confirmed with 100ns MD simulation in presence of 5mM MgCl2 ionic environment. In this environment, structural stability was significantly improved by bonded interactions between a RNA backbone and Mg2+ ions. These predictions were further validated in silico using RNA normal mode analysis and anisotropic network modelling (ANM) studies. The study may be significantly imparted to know the functional importance of many such 3'UTRs to predict their role in a mechanistic manner. PMID- 26901861 TI - Low Dialysate Calcium: Between Low Arterial Calcification and Improved Low Bone Turnover. PMID- 26901859 TI - Transcriptional Auto-Regulation of RUNX1 P1 Promoter. AB - RUNX1 a member of the family of runt related transcription factors (RUNX), is essential for hematopoiesis. The expression of RUNX1 gene is controlled by two promoters; the distal P1 promoter and the proximal P2 promoter. Several isoforms of RUNX1 mRNA are generated through the use of both promoters and alternative splicing. These isoforms not only differs in their temporal expression pattern but also exhibit differences in tissue specificity. The RUNX1 isoforms derived from P2 are expressed in a variety of tissues, but expression of P1-derived isoform is restricted to cells of hematopoietic lineage. However, the control of hematopoietic-cell specific expression is poorly understood. Here we report regulation of P1-derived RUNX1 mRNA by RUNX1 protein. In silico analysis of P1 promoter revealed presence of two evolutionary conserved RUNX motifs, 0.6kb upstream of the transcription start site, and three RUNX motifs within 170bp of the 5'UTR. Transcriptional contribution of these RUNX motifs was studied in myeloid and T-cells. RUNX1 genomic fragment containing all sites show very low basal activity in both cell types. Mutation or deletion of RUNX motifs in the UTR enhances basal activity of the RUNX1 promoter. Chromatin immunoprecipitation revealed that RUNX1 protein is recruited to these sites. Overexpression of RUNX1 in non-hematopoietic cells results in a dose dependent activation of the RUNX1 P1 promoter. We also demonstrate that RUNX1 protein regulates transcription of endogenous RUNX1 mRNA in T-cell. Finally we show that SCL transcription factor is recruited to regions containing RUNX motifs in the promoter and the UTR and regulates activity of the RUNX1 P1 promoter in vitro. Thus, multiple lines of evidence show that RUNX1 protein regulates its own gene transcription. PMID- 26901862 TI - Highly Active and Redox-Stable Ce-Doped LaSrCrFeO-Based Cathode Catalyst for CO2 SOECs. AB - Lanthanum chromate-based perovskite oxides have attracted great attention as the cathode materials in the high-temperature CO2 electrolysis because of its good redox stability. However, the unsatisfied electrochemical catalytic activity and insufficient adsorption of CO2 at operating temperature still hindered the further improvement of electrochemical performance and the Faraday efficiency of the electrolysis cell. In this work, the catalytic and redox active Ce was doped into A site of La0.7Sr0.3Cr0.5Fe0.5O3-delta (LSCrF) to promote the catalytic performance, and to introduce oxygen vacancies in the lattice in situ after reduction under the operational condition. The increased amount of oxygen vacancies not only facilitates the mobility of oxygen ions, but also provides favorable accommodation for chemical adsorption of CO2. The CO2 electrolysis tests demonstrated the superior electrochemical performances, higher Faraday efficiencies of the Ce-doped LSCrF cathode catalyst in comparison with that without Ce doping, indicating the perspective application of this functional material. PMID- 26901860 TI - Renal Function Outcomes and Risk Factors for Stage 3B Chronic Kidney Disease after Urinary Diversion in Patients with Muscle Invasive Bladder Cancer [corrected]. AB - OBJECTIVES: To assess the effects of urinary diversion on renal function, we retrospectively investigated renal function over 5 years after urinary diversion using a propensity score matching strategy. METHODS: Between May 1996 and November 2013, 345 consecutive adult patients underwent radical cystectomy and urinary diversion in our hospital; one hundred and fifteen patients with more than a 5-year follow-up were enrolled. Propensity scores were calculated using logistic analysis, and the data used in the analyses included age, gender, Eastern Cooperative Oncology Group Performance Status (ECOG-PS), clinical tumor stage, presence of cardiovascular disease; hypertension; and type 2 diabetes and preoperative eGFR at the initial visit. Multivariate logistic regression analysis was used to assess the risk factors for stage 3B chronic kidney disease (CKD) after the different types of urinary diversion. RESULTS: Continent and incontinent diversion were performed in 68 and 47 patients, respectively. The mean preoperative eGFR was significantly lower in the incontinent than in the continent group (P < 0.001). In propensity score-matched patients (n = 34 each), no significant differences were observed in pre- and postoperative eGFR and 5 year eGFR decrease rates between the groups. In the incontinent group, the number of postoperative stage 3B CKD patients was significantly increased than the continent group. Using multivariate analysis, independent risk factors significantly associated with stage 3B CKD at 5 years after surgery were older age, eGFR before surgery, incontinent diversion (cutaneous ureterostomy), and postoperative hydronephrosis. CONCLUSIONS: The types of urinary diversion had no significant impact on renal function decline, whereas older age, preexisting impaired renal function, postoperative hydronephrosis, and cutaneous ureterostomy were independent risk factors for stage 3B CKD at 5 years after radical cystectomy. PMID- 26901864 TI - Osmoregulation during Long-Term Fasting in Lungfish and Elephant Seal: Old and New Lessons for the Nephrologist. AB - Vertebrates control the osmolality of their extra- and intra-cellular compartments despite large variations in salt and water intake. Aldosterone dependent sodium reabsorption and vasopressin-dependent water transport in the distal nephron and collecting duct play a critical role in the final control of sodium and water balance. Long-term fasting (no eating, no drinking) represents an osmotic challenge for survival. Evolution has found very different solutions to meet this challenge. To illustrate this point, I will discuss osmoregulation of a mammal (elephant seal pup) and of a fish (lungfish) that are able to survive long-term fasting for months or even years. Homer W. Smith taught us how informative comparative anatomy and physiology of the kidney could help physiologists and nephrologists to better understand how the kidney works. In recent years, comparative genomics, transcriptomics and proteomics across the tree of life have led to the emergence of a new discipline, evolutionary medicine. In the near future, physiologists and nephrologists will benefit from this new field of investigation, thanks to its potential for the identification of novel drug targets and therapies. PMID- 26901863 TI - Transcriptome Sequencing (RNAseq) Enables Utilization of Formalin-Fixed, Paraffin Embedded Biopsies with Clear Cell Renal Cell Carcinoma for Exploration of Disease Biology and Biomarker Development. AB - Formalin-fixed, paraffin-embedded (FFPE) tissues are an underused resource for molecular analyses. This proof of concept study aimed to compare RNAseq results from FFPE biopsies with the corresponding RNAlater(r) (Qiagen, Germany) stored samples from clear cell renal cell carcinoma (ccRCC) patients to investigate feasibility of RNAseq in archival tissue. From each of 16 patients undergoing partial or full nephrectomy, four core biopsies, such as two specimens with ccRCC and two specimens of adjacent normal tissue, were obtained with a 16g needle. One normal and one ccRCC tissue specimen per patient was stored either in FFPE or RNAlater(r). RNA sequencing libraries were generated applying the new Illumina TruSeq(r) Access library preparation protocol. Comparative analysis was done using voom/Limma R-package. The analysis of the FFPE and RNAlater(r) datasets yielded similar numbers of detected genes, differentially expressed transcripts and affected pathways. The FFPE and RNAlater datasets shared 80% (n = 1106) differentially expressed genes. The average expression and the log2 fold changes of these transcripts correlated with R2 = 0.97, and R2 = 0.96, respectively. Among transcripts with the highest fold changes in both datasets were carbonic anhydrase 9 (CA9), neuronal pentraxin-2 (NPTX2) and uromodulin (UMOD) that were confirmed by immunohistochemistry. IPA revealed the presence of gene signatures of cancer and nephrotoxicity, renal damage and immune response. To simulate the feasibility of clinical biomarker studies with FFPE samples, a classifier model was developed for the FFPE dataset: expression data for CA9 alone had an accuracy, specificity and sensitivity of 94%, respectively, and achieved similar performance in the RNAlater dataset. Transforming growth factor-beta1 (TGFB1) regulated genes, epithelial to mesenchymal transition (EMT) and NOTCH signaling cascade may support novel therapeutic strategies. In conclusion, in this proof of concept study, RNAseq data obtained from FFPE kidney biopsies are comparable to data obtained from fresh stored material, thereby expanding the utility of archival tissue specimens. PMID- 26901865 TI - Competitive Semantic Memory Retrieval: Temporal Dynamics Revealed by Event Related Potentials. AB - Memories compete for retrieval when they are related to a common retrieval cue. Previous research has shown that retrieval of a target memory may lead to subsequent retrieval-induced forgetting (RIF) of currently irrelevant competing memories. In the present study, we investigated the time course of competitive semantic retrieval and examined the neurocognitive mechanisms underlying RIF. We contrasted two theoretical accounts of RIF by examining a critical aspect of this memory phenomenon, namely the extent to which it depends on successful retrieval of the target memory. Participants first studied category-exemplar word-pairs (e.g. Fruit-Apple). Next, we recorded electrophysiological measures of brain activity while the participants performed a competitive semantic cued-recall task. In this task, the participants were provided with the studied categories but they were instructed to retrieve other unstudied exemplars (e.g. Fruit Ma__?). We investigated the event-related potential (ERP) correlates of retrieval success by comparing ERPs from successful and failed retrieval trials. To isolate the ERP correlates of continuous retrieval attempts from the ERP correlates of retrieval success, we included an impossible retrieval condition, with incompletable word-stem cues (Drinks-Wy__) and compared it with a non-retrieval presentation baseline condition (Occupation-Dentist). The participants' memory for all the studied exemplars was tested in the final phase of the experiment. Taken together, the behavioural results suggest that RIF is independent of target retrieval. Beyond investigating the mechanisms underlying RIF, the present study also elucidates the temporal dynamics of semantic cued-recall by isolating the ERP correlates of retrieval attempt and retrieval success. The ERP results revealed that retrieval attempt is reflected in a late posterior negativity, possibly indicating construction of candidates for completing the word-stem cue and retrieval monitoring whereas retrieval success was reflected in an anterior positive slow wave. PMID- 26901867 TI - Correction: Musculoskeletal Pain as a Marker of Health Quality. Findings from the Epidemiological Sleep Study among the Adult Population of Sao Paulo City. PMID- 26901866 TI - A Component-Based Study of the Effect of Diameter on Bond and Anchorage Characteristics of Blind-Bolted Connections. AB - Structural hollow sections are gaining worldwide importance due to their structural and architectural advantages over open steel sections. The only obstacle to their use is their connection with other structural members. To overcome the obstacle of tightening the bolt from one side has given birth to the concept of blind bolts. Blind bolts, being the practical solution to the connection hindrance for the use of hollow and concrete filled hollow sections play a vital role. Flowdrill, the Huck High Strength Blind Bolt and the Lindapter Hollobolt are the well-known commercially available blind bolts. Although the development of blind bolts has largely resolved this issue, the use of structural hollow sections remains limited to shear resistance. Therefore, a new modified version of the blind bolt, known as the "Extended Hollo-Bolt" (EHB) due to its enhanced capacity for bonding with concrete, can overcome the issue of low moment resistance capacity associated with blind-bolted connections. The load transfer mechanism of this recently developed blind bolt remains unclear, however. This study uses a parametric approach to characterising the EHB, using diameter as the variable parameter. Stiffness and load-carrying capacity were evaluated at two different bolt sizes. To investigate the load transfer mechanism, a component based study of the bond and anchorage characteristics was performed by breaking down the EHB into its components. The results of the study provide insight into the load transfer mechanism of the blind bolt in question. The proposed component based model was validated by a spring model, through which the stiffness of the EHB was compared to that of its components combined. The combined stiffness of the components was found to be roughly equivalent to that of the EHB as a whole, validating the use of this component-based approach. PMID- 26901869 TI - Effect of Surface Charge on Surface-Initiated Atom Transfer Radical Polymerization from Cellulose Nanocrystals in Aqueous Media. AB - Cellulose nanocrystals (CNCs) with different charge densities were utilized to examine the role of electrostatic interactions on surface-initiated atom transfer radical polymerization (SI-ATRP) in aqueous media. To this end, growth of hydrophilic uncharged poly(N,N-dimethylacrylamide) (PDMAM) brushes was monitored by electrophoresis, (1)H NMR spectroscopy, and dynamic light scattering (DLS). Molecular weight and polydispersity of PDMAM brushes was determined by GPC analysis of hydrolytically cleaved polymers. Initiator and polymer brush grafting densities, and thus, initiator efficiencies were derived from elemental analysis. Higher initiator efficiency of polymer brush growth was observed for CNCs with higher anionic surface sulfate half-ester group density, but at the expense of high polydispersity caused by inefficient deactivation. PDMAM grafts with number average molecular weights up to 530 kDa and polydispersity indices <1.5 were obtained under highly diluted monomer concentrations. The role of surface chemistry on the growth of neutral polymer brushes from CNCs in water is emphasized and a model of the interfacial region at the onset of polymerization is proposed. The results presented here could have implications for other substrates that present surface charges and for the assumption that the kinetics of Cu-mediated SI-CRP are analogous to those conducted in solution. PMID- 26901870 TI - Change of carrier density at the pseudogap critical point of a cuprate superconductor. AB - The pseudogap is a partial gap in the electronic density of states that opens in the normal (non-superconducting) state of cuprate superconductors and whose origin is a long-standing puzzle. Its connection to the Mott insulator phase at low doping (hole concentration, p) remains ambiguous and its relation to the charge order that reconstructs the Fermi surface at intermediate doping is still unclear. Here we use measurements of the Hall coefficient in magnetic fields up to 88 tesla to show that Fermi-surface reconstruction by charge order in the cuprate YBa2Cu3Oy ends sharply at a critical doping p = 0.16 that is distinctly lower than the pseudogap critical point p* = 0.19 (ref. 11). This shows that the pseudogap and charge order are separate phenomena. We find that the change in carrier density n from n = 1 + p in the conventional metal at high doping (ref. 12) to n = p at low doping (ref. 13) starts at the pseudogap critical point. This shows that the pseudogap and the antiferromagnetic Mott insulator are linked. PMID- 26901871 TI - Structural basis of outer membrane protein insertion by the BAM complex. AB - All Gram-negative bacteria, mitochondria and chloroplasts have outer membrane proteins (OMPs) that perform many fundamental biological processes. The OMPs in Gram-negative bacteria are inserted and folded into the outer membrane by the beta-barrel assembly machinery (BAM). The mechanism involved is poorly understood, owing to the absence of a structure of the entire BAM complex. Here we report two crystal structures of the Escherichia coli BAM complex in two distinct states: an inward-open state and a lateral-open state. Our structures reveal that the five polypeptide transport-associated domains of BamA form a ring architecture with four associated lipoproteins, BamB-BamE, in the periplasm. Our structural, functional studies and molecular dynamics simulations indicate that these subunits rotate with respect to the integral membrane beta-barrel of BamA to induce movement of the beta-strands of the barrel and promote insertion of the nascent OMP. PMID- 26901872 TI - Crystal structure of eukaryotic translation initiation factor 2B. AB - Eukaryotic cells restrict protein synthesis under various stress conditions, by inhibiting the eukaryotic translation initiation factor 2B (eIF2B). eIF2B is the guanine nucleotide exchange factor for eIF2, a heterotrimeric G protein consisting of alpha-, beta- and gamma-subunits. eIF2B exchanges GDP for GTP on the gamma-subunit of eIF2 (eIF2gamma), and is inhibited by stress-induced phosphorylation of eIF2alpha. eIF2B is a heterodecameric complex of two copies each of the alpha-, beta-, gamma-, delta- and epsilon-subunits; its alpha-, beta- and delta-subunits constitute the regulatory subcomplex, while the gamma- and epsilon-subunits form the catalytic subcomplex. The three-dimensional structure of the entire eIF2B complex has not been determined. Here we present the crystal structure of Schizosaccharomyces pombe eIF2B with an unprecedented subunit arrangement, in which the alpha2beta2delta2 hexameric regulatory subcomplex binds two gammaepsilon dimeric catalytic subcomplexes on its opposite sides. A structure-based in vitro analysis by a surface-scanning site-directed photo-cross linking method identified the eIF2alpha-binding and eIF2gamma-binding interfaces, located far apart on the regulatory and catalytic subcomplexes, respectively. The eIF2gamma-binding interface is located close to the conserved 'NF motif', which is important for nucleotide exchange. A structural model was constructed for the complex of eIF2B with phosphorylated eIF2alpha, which binds to eIF2B more strongly than the unphosphorylated form. These results indicate that the eIF2alpha phosphorylation generates the 'nonproductive' eIF2-eIF2B complex, which prevents nucleotide exchange on eIF2gamma, and thus provide a structural framework for the eIF2B-mediated mechanism of stress-induced translational control. PMID- 26901873 TI - The Prevalence and Impact of Heavy Menstrual Bleeding (Menorrhagia) in Elite and Non-Elite Athletes. AB - To identify the prevalence and impact of heavy menstrual bleeding (HMB) in exercising females where anemia may have a significant effect on training and performance a 'Female Health Questionnaire' was designed incorporating a validated diagnostic HMB series, demographics, exercise ability data, training status, anemia, iron supplementation and whether the menstrual cycle had affected training and performance. The survey was conducted in two stages; initially online, advertised via social media, and then repeated via face-to-face interviews with runners registered for the 2015 London Marathon. 789 participants responded to the online survey, and 1073 completed the survey at the marathon. HMB was reported by half of those online (54%), and by more than a third of the marathon runners (36%). Surprisingly, HMB was also prevalent amongst elite athletes (37%). Overall, 32% of exercising females reported a history of anemia, and 50% had previously supplemented with iron. Only a minority (22%) had sought medical advice. HMB is highly prevalent in exercising females, associated with self-reported anemia, increased use of iron supplementation and a perceived negative impact on performance. Further research is needed to investigate the impact of HMB, iron deficiency and anemia in exercising females. PMID- 26901874 TI - Alagille Syndrome Candidates for Liver Transplantation: Differentiation from End Stage Biliary Atresia Using Preoperative CT. AB - PURPOSE: To compare preoperative CT findings before liver transplantation between patients with Alagille syndrome (AGS) and those with end-stage biliary atresia (BA). MATERIALS AND METHODS: The institutional review board approved this retrospective study. Eleven children with AGS (median age, 19.0 +/- 13.0 months; male to female ratio, 3:8) and 109 children with end-stage BA (median age, 17.9 +/- 25.8 months; male to female ratio, 37:72) who underwent abdomen CT as candidates for liver transplant were included. CT images were reviewed focusing on hepatic parenchymal changes, vascular changes, presence of focal lesions, and signs of portal hypertension. RESULTS: Hepatic parenchymal changes were present in 27% (3/11) of AGS patients and 100% (109/109) of end-stage BA patients (P < .001). The hepatic artery diameter was significantly smaller (1.9 mm versus 3.6 mm, P = 008), whereas portal vein diameter was larger (6.8 mm versus 5.0 mm, P < .001) in patients with AGS compared with patients with end-stage BA. No focal lesion was seen in patients with AGS, whereas 44% (48/109) of patients with end stage BA had intrahepatic biliary cysts (39%, 43/109) and hepatic tumors (8%, 9/109) (P = .008). Splenomegaly was commonly seen in both groups (P = .082), and ascites (9% [1/11] versus 50% [54/109], P = .010) and gastroesophageal varix (0% [0/11] versus 80% [87/109], P < .001) were less common in patients with AGS than in patients with end-stage BA. CONCLUSION: Fibrotic or cirrhotic changes of the liver, presence of focal lesions, and relevant portal hypertension were less common in patients with AGS than in patients with end-stage BA. PMID- 26901876 TI - Relating Doses of Contrast Agent Administered to TIC and Semi-Quantitative Parameters on DCE-MRI: Based on a Murine Breast Tumor Model. AB - OBJECTIVE: To explore the changes in the time-signal intensity curve(TIC) type and semi-quantitative parameters of dynamic contrast-enhanced(DCE)imaging in relation to variations in the contrast agent(CA) dosage in the Walker 256 murine breast tumor model, and to determine the appropriate parameters for the evaluation ofneoadjuvantchemotherapy(NAC)response. MATERIALS AND METHODS: Walker 256 breast tumor models were established in 21 rats, which were randomly divided into three groups of7rats each. Routine scanning and DCE-magnetic resonance imaging (MRI) of the rats were performed using a 7T MR scanner. The three groups of rats were administered different dosages of the CA0.2mmol/kg, 0.3mmol/kg, and 0.5mmol/kg, respectively; and the corresponding TICs the semi-quantitative parameters were calculated and compared among the three groups. RESULTS: The TICs were not influenced by the CA dosage and presented a washout pattern in all of the tumors evaluated and weren't influenced by the CA dose. The values of the initial enhancement percentage(Efirst), initial enhancement velocity(Vfirst), maximum signal(Smax), maximum enhancement percentage(Emax), washout percentage(Ewash), and signal enhancement ratio(SER) showed statistically significant differences among the three groups (F = 16.952, p = 0.001; F = 69.483, p<0.001; F = 54.838, p<0.001; F = 12.510, p = 0.003; F = 5.248, p = 0.031; F = 9.733, p = 0.006, respectively). However, the values of the time to peak(Tpeak), maximum enhancement velocity(Vmax), and washout velocity(Vwash)did not differ significantly among the three dosage groups (F = 0.065, p = 0.937; F = 1.505, p = 0.273; chi2 = 1.423, p = 0.319, respectively); the washout slope(Slopewash), too, was uninfluenced by the dosage(F = 1.654, p = 0.244). CONCLUSION: The CA dosage didn't affect the TIC type, Tpeak, Vmax, Vwash or Slopewash. These dose-independent parameters as well as the TIC type might be more useful for monitoring the NAC response because they allow the comparisons of the DCE data obtained using different CA dosages. PMID- 26901875 TI - Shoulder dystocia: prediction and management. AB - Shoulder dystocia is a complication of vaginal delivery and the primary factor associated with brachial plexus injury. In this review, we discuss the risk factors for shoulder dystocia and propose a framework for the prediction and prevention of the complication. A recommended approach to management when shoulder dystocia occurs is outlined, with review of the maneuvers used to relieve the obstruction with minimal risk of fetal and maternal injury. PMID- 26901877 TI - Key Role of Sequencing to Trace Hepatitis A Viruses Circulating in Italy During a Large Multi-Country European Foodborne Outbreak in 2013. AB - BACKGROUND: Foodborne Hepatitis A Virus (HAV) outbreaks are being recognized as an emerging public health problem in industrialized countries. In 2013 three foodborne HAV outbreaks occurred in Europe and one in USA. During the largest of the three European outbreaks, most cases occurred in Italy (>1,200 cases as of March 31, 2014). A national Task Force was established at the beginning of the outbreak by the Ministry of Health. Mixed frozen berries were early demonstrated to be the source of infection by the identity of viral sequences in patients and in food. In the present study the molecular characterization of HAV isolates from 355 Italian cases is reported. METHODS: Molecular characterization was carried out by PCR/sequencing (VP1/2A region), comparison with reference strains and phylogenetic analysis. RESULTS: A unique strain was responsible for most characterized cases (235/355, 66.1%). Molecular data had a key role in tracing this outbreak, allowing 110 out of the 235 outbreak cases (46.8%) to be recognized in absence of any other link. The data also showed background circulation of further unrelated strains, both autochthonous and travel related, whose sequence comparison highlighted minor outbreaks and small clusters, most of them unrecognized on the basis of epidemiological data. Phylogenetic analysis showed most isolates from travel related cases clustering with reference strains originating from the same geographical area of travel. CONCLUSIONS: In conclusion, the study documents, in a real outbreak context, the crucial role of molecular analysis in investigating an old but re-emerging pathogen. Improving the molecular knowledge of HAV strains, both autochthonous and circulating in countries from which potentially contaminated foods are imported, will become increasingly important to control outbreaks by supporting trace back activities, aiming to identify the geographical source(s) of contaminated food, as well as public health interventions. PMID- 26901878 TI - Population Genetic Structure of the Magnificent Frigatebird Fregata magnificens (Aves, Suliformes) Breeding Colonies in the Western Atlantic Ocean. AB - The Magnificent Frigatebird Fregata magnificens has a pantropical distribution, nesting on islands along the Atlantic and Pacific coasts. In the Caribbean, there is little genetic structure among colonies; however, the genetic structure among the colonies off Brazil and its relationship with those in the Caribbean are unknown. In this study, we used mtDNA and microsatellite markers to infer population structure and evolutionary history in a sample of F. magnificens individuals collected in Brazil, Grand Connetable (French Guyana), and Barbuda. Virtually all Brazilian individuals had the same mtDNA haplotype. There was no haplotype sharing between Brazil and the Caribbean, though Grand Connetable shared haplotypes with both regions. A Bayesian clustering analysis using microsatellite data found two genetic clusters: one associated with Barbuda and the other with the Brazilian populations. Grand Connetable was more similar to Barbuda but had ancestry from both clusters, corroborating its "intermediate" position. The Caribbean and Grand Connetable populations showed higher genetic diversity and effective population size compared to the Brazilian population. Overall, our results are in good agreement with an effect of marine winds in isolating the Brazilian meta-population. PMID- 26901879 TI - Visual Acceleration Perception for Simple and Complex Motion Patterns. AB - Humans are able to judge whether a target is accelerating in many viewing contexts, but it is an open question how the motion pattern per se affects visual acceleration perception. We measured acceleration and deceleration detection using patterns of random dots with horizontal (simpler) or radial motion (more visually complex). The results suggest that we detect acceleration better when viewing radial optic flow than horizontal translation. However, the direction within each type of pattern has no effect on performance and observers detect acceleration and deceleration similarly within each condition. We conclude that sensitivity to the presence of acceleration is generally higher for more complex patterns, regardless of the direction within each type of pattern or the sign of acceleration. PMID- 26901881 TI - Fat Imaging via Magnetic Resonance Imaging (MRI) in Young Children (Ages 1-4 Years) without Sedation. AB - INTRODUCTION: This pilot study developed techniques to perform Magnetic Resonance Imaging (MRI) of specific fat deposition in 18 children (age 18 months to 4 years). METHODS: The children engaged in a series of practice tests to become acclimated to the scanner noises, reduce claustrophobia, and rehearse holding still for a set time. The practice tests assessed if the child could remain still for two minutes while watching a video, first while lying on a blanket, second, on the blanket with headphones, and third, in the mock scanner. The children who passed the three practice tests were then scanned with a 3T Siemens Skyra magnet. Abdominal fat distribution (region of interest (ROI) from the top of the ileac crest to the bottom of the ribcage) volume was measured using 2-point DIXON technique. This region was chosen to give an indication of the body composition around the liver. RESULTS: Twelve out of eighteen participants successfully completed the actual MRI scan. Chi-squared test showed no significant difference between male and female pass-fail rates. The median age of completed scans was 36 months, whereas the median age for children unable to complete a scan was 28 months. The average total trunk fat was 240.9+/-85.2mL and the average total VAT was 37.7+/-25.9mLand liver fat was not quantifiable due to physiological motion. Several strategies (modeling, videos, and incentives) were identified to improve pediatric imaging in different age ranges. CONCLUSION: Using an age-specific and tailored protocol, we were able to successfully use MRI for fat imaging in a majority of young children. Development of such protocols enables researchers to better understand the etiology of fat deposition in young children, which can be used to aid in the prevention and treatment of adiposity. PMID- 26901880 TI - Control of betaAR- and N-methyl-D-aspartate (NMDA) Receptor-Dependent cAMP Dynamics in Hippocampal Neurons. AB - Norepinephrine, a neuromodulator that activates beta-adrenergic receptors (betaARs), facilitates learning and memory as well as the induction of synaptic plasticity in the hippocampus. Several forms of long-term potentiation (LTP) at the Schaffer collateral CA1 synapse require stimulation of both betaARs and N methyl-D-aspartate receptors (NMDARs). To understand the mechanisms mediating the interactions between betaAR and NMDAR signaling pathways, we combined FRET imaging of cAMP in hippocampal neuron cultures with spatial mechanistic modeling of signaling pathways in the CA1 pyramidal neuron. Previous work implied that cAMP is synergistically produced in the presence of the betaAR agonist isoproterenol and intracellular calcium. In contrast, we show that when application of isoproterenol precedes application of NMDA by several minutes, as is typical of betaAR-facilitated LTP experiments, the average amplitude of the cAMP response to NMDA is attenuated compared with the response to NMDA alone. Models simulations suggest that, although the negative feedback loop formed by cAMP, cAMP-dependent protein kinase (PKA), and type 4 phosphodiesterase may be involved in attenuating the cAMP response to NMDA, it is insufficient to explain the range of experimental observations. Instead, attenuation of the cAMP response requires mechanisms upstream of adenylyl cyclase. Our model demonstrates that Gs to-Gi switching due to PKA phosphorylation of betaARs as well as Gi inhibition of type 1 adenylyl cyclase may underlie the experimental observations. This suggests that signaling by beta-adrenergic receptors depends on temporal pattern of stimulation, and that switching may represent a novel mechanism for recruiting kinases involved in synaptic plasticity and memory. PMID- 26901883 TI - [Exploration of Renal Microcirculation Perfusion During Cardiopulmonary Bypass with Contrast-enhanced Ultrasound]. AB - OBJECTIVE: To investigate the alteration of renal microcirculation perfusion during cardiopulmonary bypass (CPB) in adult patients with contrast-enhanced ultrasound (CEU). METHODS: Six patients undergoing cardiac surgery with CPB and twelve patients undergoing non-cardiac surgery were enrolled and classified into CPB group and control group. CEU images of kidney were collected at the point of 30 min after CPB or 5 min after anesthesia induction respectively. Time intensity curve (TIC) was derived from three regions of interest (ROD. superficial cortex, deep cortex and medulla. Parameters including wash in slope (a), area under curve (AUC), peak intensity (PI) and time to peak (TTP) were calculated based on gamma variant function. RESULTS: CEU showed a significant reduction of AUC in all three regions (superficial cortex, deep cortex and medulla) during CPB, compared with anesthetic condition. Ultrasound contrast agent-related adverse reactions were not occurred in all enrolled patients. CONCLUSION: Renal microcirculation perfusion was dramatically reduced during CPB, especially in the medulla. CEU could be detected the renal microcirculation perfusion in the perioperative period of cardiac surgery. PMID- 26901884 TI - [Reliability and Validity of Function Score for Adult Tibetans with Kashin Beck Disease in Aba Tibetan Autonomous Area in Sichuan Province]. AB - OBJECTIVE: To validate the function score for adult Tibetans with Kashin-Beck disease (FSAT- KBD) measuring daily life and work functional status of KBD patients. METHODS: From September to October 2010, 352 adult KBD patients in Rangtang County of Aba Tibetan autonomous region were invited to complete FSAT KBD. The internal consistency of FSAT-KBD was assessed using Cronbach's alpha coefficients. Principal component analysis with varimax rotation was performed to explore factor structure of the instrument, with item-domain correlations being examined using Spearman's rank correlation tests. Discriminant validity of the FSAT-KBD was assessed by comparing scores of the respondents with different ages and different functional status. Convergent validity of the FSAT-KBD was assessed through a comparison with the medical outcomes study short form health survey (SF 12) and visual analogue scale (VAS). RESULTS: 338 KBD patients (a response rate of 96.0%) completed the questionnaire in an average of (3.2 +/- 1.6) min. The instrument achieved a Cronbach's alpha of 0.945, with item-to-domain correlations exceeding 0.0. Two latent factors were extracted, which explained 72.8% of the total variance. The factor structure fitted well with our conceptual hypothesis. Respondents with different age, duration of suffering and number of affected joints had different FSAT-KBD scores. The FSAT-KBD results were correlated with those of SF-12 and VAS. CONCLUSION: FSAT-KBD is a reliable and valid instrument for measuring daily functional status of adult KBD patients in Aba Tibetan autonomous area in China. PMID- 26901885 TI - STFM launches initiative in response to faculty shortage. PMID- 26901882 TI - Reverse Genetics for Fusogenic Bat-Borne Orthoreovirus Associated with Acute Respiratory Tract Infections in Humans: Role of Outer Capsid Protein sigmaC in Viral Replication and Pathogenesis. AB - Nelson Bay orthoreoviruses (NBVs) are members of the fusogenic orthoreoviruses and possess 10-segmented double-stranded RNA genomes. NBV was first isolated from a fruit bat in Australia more than 40 years ago, but it was not associated with any disease. However, several NBV strains have been recently identified as causative agents for respiratory tract infections in humans. Isolation of these pathogenic bat reoviruses from patients suggests that NBVs have evolved to propagate in humans in the form of zoonosis. To date, no strategy has been developed to rescue infectious viruses from cloned cDNA for any member of the fusogenic orthoreoviruses. In this study, we report the development of a plasmid based reverse genetics system free of helper viruses and independent of any selection for NBV isolated from humans with acute respiratory infection. cDNAs corresponding to each of the 10 full-length RNA gene segments of NBV were cotransfected into culture cells expressing T7 RNA polymerase, and viable NBV was isolated using a plaque assay. The growth kinetics and cell-to-cell fusion activity of recombinant strains, rescued using the reverse genetics system, were indistinguishable from those of native strains. We used the reverse genetics system to generate viruses deficient in the cell attachment protein sigmaC to define the biological function of this protein in the viral life cycle. Our results with sigmaC-deficient viruses demonstrated that sigmaC is dispensable for cell attachment in several cell lines, including murine fibroblast L929 cells but not in human lung epithelial A549 cells, and plays a critical role in viral pathogenesis. We also used the system to rescue a virus that expresses a yellow fluorescent protein. The reverse genetics system developed in this study can be applied to study the propagation and pathogenesis of pathogenic NBVs and in the generation of recombinant NBVs for future vaccines and therapeutics. PMID- 26901886 TI - NAPCRG congratulates the 2014 Patient Choice Award winners. PMID- 26901887 TI - Sex Differences in Incline-Walking among Humans. AB - Previous research has shown that people tend to walk around the speed that minimizes energy consumption when traveling a given distance. It has further been shown that men and women have different speeds that minimize energy and that women will choose slower speeds when the activity itself is a high-rate activity (e.g. carrying a load). Here we investigate what men and women will do when given a high rate walking activity, namely walking on an inclined surface. Fourteen people (nine men and five women) walked at four speeds on a level treadmill and four speeds on an inclined treadmill while their metabolic rate, kinematics and core temperature were monitored. Following the data collection, participants were asked to identify their 'preferred' walking speed at each of the conditions. Cost of transport (CoT) curves were calculated for each individual, and the delta between the preferred and the 'optimal' speeds were calculated. People chose to walk at slightly slower speeds on the level; there was minimal change in the cost to walk at these slower speeds. Women walked at absolutely slower speeds on the incline than men (P=0.06) and had significantly larger speed deltas (P=0.02), thus choosing to walk at slower rate speeds. Women also showed a significant relationship between the rate of activity and core temperature, whereas men did not. This is consistent with other research showing that women choose behavioral strategies to minimize body temperature changes. PMID- 26901888 TI - [Analysis of the genome sequences of Dengue virus caused an outbreak of Dengue Fever in Henan province, 2013]. PMID- 26901889 TI - [A Case with Multiple Comorbidities of Obsessive-Compulsive and Related Disorders]. AB - Obsessive-compulsive and related disorders (OCRDs) have been introduced in a revision to DSM-5 as a novel category that is distinct from other anxiety disorders in DSM-IV. OCRDs consist of 5 primary disorders: obsessive-compulsive disorder (OCD), body dysmorphic disorder (BDD), hoarding disorder (HD), skin picking disorder (SPD), and hair pulling disorder (HPD), which share core clinical features such as preoccupation or recurrent thoughts and/or repetitive behaviors. Repetitive behaviors in BDD and HD can be differentially characterized by the presence of cognitive components associated with preceding anxiety from those in SPD or HPD, which are only observed as motoric components that regulate emotions or alleviate tension. Thus, the validity of the OCRD category and specific interrelationships between each OCRD remain uncertain. In the present study, therefore, we presented a case of multiple comorbidities of OCRDs in order to discuss the nature of the OCRD category. Our patient was a 20-year-old female university student. At the age of 11 years old, she started picking at acne on her face. The psychopathological, and treatment features observed in this case indicated possible interrelationships among OCRDs, especially between cognitive and motoric OCRDs, which supported the clinical utility and continuous nature of this category. PMID- 26901890 TI - [Perinatal Depression: The Meaning of the Paradigm Shift from "Postnatal" to "Perinatal"]. AB - Psychiatry regarding pregnancy, childbirth, and child-rearing is changing rapidly. In this paper, the meaning of the paradigm shift from postnantal to perinatal depression along with the changing treatment are discussed. Since the late 20 century, several large-scale epidemiological surveys on the incidence and outcomes of postnatal depression have concluded not only that postpartum depression is likely to occur at a high frequency, such as 10-15%, but that the subsequent maternal mortality rate as the number of deaths from suicide is higher than deaths due to obstetric medical conditions. Additionally, evidence of the negative impact of a mother's depression on the physical and mental development of children has been accumulated as well. Several studies regarding depression during pregnancy, such as on the relatively high frequency of prenatal depression or negative consequence of interrupted pharmacological treatment, should also be highlighted. These movements seemed to reflect the change in special attributes of depressive disorders and bipolar disorders, in that the term perinatal onset came to be preferred instead of postnatal, used in DSM-IV. Comprehensive treatment guidelines for depression applicable for all women with the potential for pregnancy, delivery, and lactation are needed as the next step. PMID- 26901891 TI - [Supporting the Love, Marriage, and Child-Rearing of Persons with Schizophrenia]. AB - Persons with schizophrenia and their families have strong interests and hopes for love, marriage, pregnancy, and child-rearing. These experiences often lead to recovery from schizophrenia. There are many partners with schizophrenia who enjoy fruitful lives even with their disability. However, only some persons can enter into such lives in the real world in Japan and other countries. This leads persons with schizophrenia to develop a discouraged and disappointed attitude, and also causes professionals of mental health to develop indifference or pessimism about these issues. Schizophrenics are thought to have interests in love and sexual behavior just as strong as the general population. I discuss with my patients about these issues and working life early in the course of treatment. Because they lose their chance to learn adult behavior in social lives with peers due to the beginning of schizophrenia, they need an opportunity to participate in a social situation to learn knowledge and skills of dating and related behaviors, and systematic education such as psycho-education and social skills training should be provided. Continuing married life and child-rearing require more support from experts with rich experience and knowledge. Psychiatrists are required to participate in shared decision-making about medication during pregnancy and breast-feeding, as well as provide knowledge on the benefits and risks of antipsychotics. Net-working with the family, professionals of child welfare, and the community is necessary to support child-rearing. Urakawa Bethel's House was introduced as a pioneering concept to support love, marriage, and child-rearing. Finally, professionals' negative or indifferent attitudes toward these issues are discussed in the setting of treatment. I hope that professionals of mental health will think about these issues from the standpoints of persons with schizophrenia and their families. PMID- 26901892 TI - [Monitoring and Care of Expectant Mothers with Epilepsy]. AB - Women with epilepsy are exposed to social stigma, and they have anxiety and lose self-confidence in their social role as a woman. Psychiatrists, especially female psychiatrists, are able to support them. Important considerations are: 1) Pre pregnant counseling; Physicians give appropriate advice and guidance. We need to provide the latest information on the teratogenicity of AEDs, and replace them with a safer combination of AEDs BEFORE pregnancy. Folate supplementation is also recommended. 2) Management during pregnancy: Patients are advised to adhere to taking AEDs as instructed, which prevents not only seizures during pregnancy but also reduces the risk of miscarriage and premature delivery. Doses of AED are to be increased after the second trimester. 3) Collaborating with obstetricians at delivery: Obstetricians are also nervous when faced with women with epilepsy. Basically, patients can deliver spontaneously, and the correct way to deal with unexpected seizures during labor should be fully understood. 4) Parental care: women with epilepsy can breastfeed. Physicians advise other family members on how to bottle feed at night to help mothers avoid a lack of sleep due to breastfeeding. Childcare is one of the most precious experiences in life. Patients with epilepsy, especially women, have a lower self-esteem; however, once they experience delivery, they act positively and become even-tempered. Physicians should be aware that childcare fosters a profound insight into their lives, allowing them to mature as a person. PMID- 26901893 TI - [Adverse Sensory Input of Childhood Maltreatment Modified by Early Experience Ascertaining the Neural Basis of Neurodevelopmental and Attachment Disorders]. AB - Childhood maltreatment, which markedly increases the risk of psychopathology such as depression, PTSD, and reduced cognitive abilities, is associated with structural and functional brain differences. Our earlier studies elucidated potential discernible effects on the brain morphology of childhood maltreatment on the gray matter volume or cortical thickness. Further, our preliminary studies revealed a significantly reduced gray matter volume (GMV) in the left primary visual cortex (Brodmann area 17) in the reactive attachment disorder (RAD) group compared to the typically developed group. These visual cortex GMV abnormalities may also be associated with such visual stimulus-induced emotion regulation impairments of RAD, leading to an increase in the risk of future psychopathology. Brain regions that process and convey the adverse sensory input of the abuse might be modified specifically by such experiences, particularly in subjects exposed to a single type of maltreatment. Thus, exposure to multiple types of maltreatment is more commonly associated with morphological alterations in corticolimbic regions. PMID- 26901894 TI - Determinants of Left Ventricular Mass Regression in Patients with Severe Symptomatic Aortic Stenosis Undergoing Transcatheter Aortic Valve Implantation. AB - BACKGROUND AND AIM OF THE STUDY: The dynamics of left ventricular mass (LVM) regression following the relief of chronic left ventricular pressure overload are prone to variation. The study aim was to identify determinants of LVM regression following transcatheter aortic valve implantation (TAVI). METHODS: A total of 134 patients undergoing TAVI was identified. A retrospective analysis was performed of LVM indexed to body surface area (LVMi), calculated using transthoracic echocardiography at baseline and at six to 12 months post-TAVI. RESULTS: At six to 12 months after TAVI, there was a significant reduction in mean LVMi (from 118.2 +/- 26.67 g/m2 to 103.4 +/- 27.07 g/m2; p < 0.001) driven by a decrease in left ventricular wall thickness. The relative wall thickness (RWT) was decreased (0.54 +/- 0.10 cm versus 0.51 +/- 0.09 cm; p = 0.006), whereas the prevalence of concentric remodeling (RWT >= 0.42) remained unchanged (85.1% versus 80.6%; p = 0.3). However, 47 patients (35.1%) demonstrated significant LVMi regression, but had a lower baseline LVMi than patients who demonstrated significant regression (109.8 +/- 25.8 g/m2 versus 122 +/- 26.1 g/m2; p = 0.008) but had otherwise similar characteristics. A greater magnitude of LVMi reduction was associated with a greater baseline LVMi (r = 0.39; p < 0.001), where patients with LVMi in the highest quartile had the most substantial reduction in LVMi (p < 0.001). Multivariable analysis identified pre-TAVI LVMi as the sole independent predictor of LVMi regression at six to 12 months post-TAVI (P = 0.45; 95% confidence interval 0.255-0.534; p < 0.001). CONCLUSION: LVM regression at six to months post-TAVI was variable, with about one-third of patients not showing a significant regression. Only baseline LVM predicted LVM regression; patients with a higher baseline LVM demonstrated a greater regression. PMID- 26901895 TI - Analysis of Specified Bernoulli Constant for Semilunar Valve Stenosis in Humans. AB - BACKGROUND AND AIM OF THE STUDY: To date, no study has determined the specified Bernoulli constant (K) and validated the simplified Bernoulli equation for semilunar valve stenosis by simultaneous measurement of peak jet flow velocity and maximum pressure gradient in humans. METHODS: Using multisensor catheters, the relationship between the peak jet flow velocity (V) and maximum-pressure gradient (max-PG) across the stenosis were analyzed, and K-values calculated for patients with pulmonary (n = 37) and aortic (n = 6) valve stenosis, who were stratified by max-PG into two groups: max-PG 50 mmHg (n = 28; group A) and those with max-PG > 50 mmHg (n = 15; group B). RESULTS: The specified constant K obtained for max-PG with peak jet flow velocity squared (V2) was 3.9, which was very close to the simplified Bernoulli constant (= 4.0), with a wide distribution in K-value for max-PG (median [interquartile range]: 3.9 [3.0-4.5]). Although there were no significant differences in specified K-values between two groups (p = 0.216), the values of K were significantly more widely scattered in group A than in group B (3.4 [2.5-4.8] versus 4.1 [3.8-4.4]; p < 0.001). CONCLUSION: The study results confirmed that, the more severe the stenosis the better suited the simplified Bernoulli constant (K = 4.0) could be for assessing semilunar valve stenosis. This result is consistent with the fluid-mechanical theorem that the kinetic energy of the jet (1/2) rhoV92) (= 4.0V(2)) produced by the stenosis disappears completely only downstream of the severe semilunar valve stenosis. PMID- 26901896 TI - Concurrent Transcatheter Aortic Valve Implantation and Percutaneous Transvenous Mitral Commissurotomy for Totally Percutaneous Treatment of Combined Severe Rheumatic Aortic and Mitral Stenosis. AB - Transcatheter aortic valve implantation (TAVI) is a new promising therapeutic option for patients with symptomatic severe calcific aortic valve stenosis (AS) who are inoperable or at high risk for conventional cardiac surgery. Percutaneous transvenous mitral commissurotomy (PTMC) is performed routinely in patients with severe mitral stenosis (MS) having a favorable anatomy. Although concurrent TAVI and PTMC is a theoretically possible approach in the treatment of patients with severe AS and MS who are unsuitable for conventional surgery, no cases have yet been reported in which this combined technique is used. For patients with severe AS and MS, the standard therapy is replacement of both the mitral and aortic valves. Herein are presented the details of a 52-year-old woman with urethral carcinoma, in whom simultaneous TAVI and PTMC was the chosen technique to treat combined severe rheumatic AS and MS in a single procedure. PMID- 26901897 TI - Reimplantation Technique: A New Approach to Increase Aortic Valve Coaptation. AB - The reimplantation technique is one of the most popular valve-sparing procedures. Previously published in-vitro studies have demonstrated the success of the aortic interleaflets triangle reshaping approach in increasing the coaptation surface. An alternative positioning of the pledgeted stitches used in the proximal suture line of the David operation is proposed to simultaneously stabilize the annulus and improve the valve functional reserve in case of annulo-aortic ectasia due to dilation of the interleaflet triangles. PMID- 26901898 TI - Gerbode Defect as a Result of Fungal Aortic Valve Endocarditis. AB - A 63-year-old male patient with HIV disease presented with dyspnea and complete heart block, and was found to have aortic valve (AV) endocarditis secondary to Candida parapsilosis infection. Echocardiography demonstrated AV endocarditis and possible aortic root versus subannular abscess with moderate AV regurgitation (AR), a ventricular septal defect (VSD) and possible left ventricular to right atrial shunt (Gerbode defect). Large AV vegetations, subannular abscess with an acquired membranous VSD, Gerbode defect, and tricuspid annular abscess at the insertion of septal leaflet were noted intraoperatively. The patient underwent AV replacement with a stented bioprosthesis, two-sided VSD patch closure, and tricuspid valve (TV) repair with an annuloplasty ring. The left-sided patch closed the VSD and facilitated AV replacement, while the right-sided patch facilitated the TV repair. PMID- 26901899 TI - Results and Quality of Life after Minimally Invasive Ross Procedure. AB - BACKGROUND AND AIM OF THE STUDY: Based on superior long-term results, an increasing interest in the Ross procedure for young adult patients can be observed. After the first publication of this challenging procedure through a minimally invasive access, this operation has become an alternative to conventional sternotomy at the authors' department. This analysis compares the results and quality of life of the conventional and the minimally invasive Ross procedures. METHODS: By April 2013, a total of 136 patients had undergone the Ross procedure at the authors' institution. Preoperative parameters did not differ between the conventional group (C-group; n = 58; mean age 49 years) and the minimally invasive group (M-group; n = 78; mean age 50 years). Only the aortic cross-clamp time was longer for the M-group (151 versus 140 min). RESULTS: One C-group patient died on the day of operation. Consecutively, survival was 99% for the follow up period of 1,093 +/- 601 days. Valve-related reoperations were necessary for four patients. One C-group patient developed a distal pulmonary stenosis due to fibrotic scar tissue. Two M-group patients showed fistulas after early endocarditis, but the native valves could be preserved in these cases. One C-group patient with recurrent severe aortic regurgitation showed holes in two of three cusps. The SF-36 questionnaire detected better physical parameters (physical function, physical role function) for patients after minimally invasive access. CONCLUSION: The minimally invasive Ross procedure allows the same excellent clinical outcome as the conventional technique. However, the physical quality of life is better with the minimally invasive procedure, in addition to an improved cosmetic result. PMID- 26901900 TI - Aortic Valve Replacement in Patients with End-Stage Liver Disease: A Modified Perfusion Concept in High-Risk Patients. AB - BACKGROUND AND AIM OF THE STUDY: Cardiac surgery with the use of cardiopulmonary bypass in patients with end-stage liver disease is associated with a high risk of postoperative morbidity and mortality due to bleeding, and a high incidence of bacterial infection with associated secondary complications. Minimized extracorporeal perfusion circuits (MECCs) with a lower priming volume, reduced foreign surface area, and interdisciplinary preoperative and postoperative treatment may address these negative effects and improve patient outcomes. The study aim was to evaluate the feasibility of the MECC and optimized supportive therapy in patients with advanced-stage liver cirrhosis. METHODS: Seven consecutive male patients (median age 56 years; range 54-67 years) with hepatic cirrhosis (Child-Pugh score B, median Model of End-stage Liver Disease (MELD) score 14; range 8-26) underwent aortic valve replacement (AVR) using MECC. Supportive preoperative and postoperative management included digestive decontamination, antioxidant supplements, and adjusted anti-infective therapy. RESULTS: All patients survived the hospital course, with 30-, 60-, and 90-day mortality of 0%. The median intensive care unit and in-hospital lengths of stay were 3 days (range: 1-5 days) and 13 days (range: 5-18 days), respectively. One patient required reexploration due to bleeding, and another suffered from a seizure without permanent neurologic deficits. No patient required new-onset hemodialysis. At a median follow up of 22 months (range: 2-46 months) all patients were alive but displayed only minor improvements in cardiac symptoms (median NYHA class III (range: II-III) at baseline versus II (range: II-III) postoperatively) and hepatic symptoms. CONCLUSION: Conventional AVR in patients with advanced-stage liver cirrhosis using MECC and optimal medical treatment is feasible. Further studies are required to evaluate the impact of alternative interventional techniques in this high-risk cohort. PMID- 26901901 TI - Large Abdominal Aortic Aneurysm in a High-Risk Surgical Patient: Combined Percutaneous Transfemoral TAVI and EVAR Procedure. AB - A 78-year-old man was referred for surgical treatment of a 55 x 59 mm abdominal aortic aneurysm (AAA). However, clinical and instrumental data revealed a more complex case than was initially thought, the patient having a large AAA in the setting of severe symptomatic aortic stenosis with multiple comorbidities. Following multidisciplinary discussion, a combined transcatheter aortic valve implantation and endovascular aneurysm repair was performed. The present case represents a good example of the importance of the heart team in the project of tailored operative strategies, and in the optimization of the interventional therapy for the individual patient. PMID- 26901902 TI - Emergent Percutaneous Biventricular Support during Transcatheter Aortic Valve Replacement. AB - Coronary obstruction following transcatheter aortic valve replacement (TAVR) is a dreaded complication which occurs in less than 1% of the procedures. Temporary hemodynamic support may be required in cases of hemodynamic collapse while performing a high-risk percutaneous coronary intervention in these patients. A challenging case is described where emergent percutaneous biventricular support (Tandem Heart for right ventricular support and Impella CPTM for left ventricular support) was used as a bridge to recovery in a patient with coronary obstruction during TAVR with the Edwards SAPIEN prosthesis. PMID- 26901903 TI - Percutaneous Mitral Valve Repair with the MitraClip System in Mitral Regurgitation Due to Mitral Annular Calcification. AB - Percutaneous valve repair with the MitraClip represents a new and promising therapeutic option for patients with severe mitral regurgitation (MR). Mitral valve prolapse and flail leaflet are two major causes of degenerative MR in patients who underwent the MitraClip procedure. Mitral annular calcification (MAC) is also a less-frequent cause of degenerative MR. Among patients with MAC, open surgical treatment or valvular replacement is the treatment of choice for severe MR. Herein we present a case with severe MR secondary to MAC in whom successful percutaneous valve repair was accomplished with the MitraClip system due to the high risk of open-heart surgery. PMID- 26901904 TI - Mitral Valve Replacement with Half-and-Half Technique for Recurrent Mitral Paravalvular Leakage. AB - Reoperation for paravalvular leakage can cause recurrent paravalvular leakage through severe damage to the mitral annulus. Previously, mitral valve replacement using a half-and-half technique for extensive mitral annular calcification was reported; here, application of the technique to treat recurrent paravalvular leakage is described. A 78-year-old male with three prior mitral valve replacements developed recurrent paravalvular leakage, for which he had undergone his third mitral valve replacement at the age of 69 years. On this occasion, a mechanical valve with circumferential equine pericardial patch reinforcement of the annulus had been used. Five years later, the patient developed hemolytic anemia and congestive heart failure due to recurrent paravalvular leakage. Intraoperatively, broad dehiscence was seen between the prosthetic valve and mitral annulus at two sites, the anterior and posterior commissures, without infection. A fourth mitral valve replacement was performed with a St. Jude Medical valve, using a half-and-half technique. This entailed the use of non everting mattress sutures on the anterior half of the annulus, and everting mattress sutures on the left atrial wall around the posterior half of the annulus. Extensive annular defects required reinforcement of the posterior mitral annulus with a bovine pericardial patch. Postoperative echocardiography showed no paravalvular leakage. The half-and-half technique may be useful in treating recurrent paravalvular leakage of the mitral valve. PMID- 26901905 TI - Vanishing V-Wave: Percutaneous Edge-to-Edge Repair for Severe Mitral Regurgitation. AB - Transcatheter mitral valve repair is an effective treatment option for patients with symptomatic mitral regurgitation and high surgical risk. Typically, transcatheter mitral valve repair is less effective in reducing mitral regurgitation severity compared to surgical mitral valve repair. Herein is presented a case of complete resolution of mitral regurgitation, as assessed by Doppler echocardiography and left atrial V-wave. PMID- 26901906 TI - Sleep Apnea in Patients with Rheumatic Mitral Stenosis. AB - BACKGROUND AND AIM OF THE STUDY: It was hypothesized that sleep disorders might be present due to functional heart failure in patients with mitral stenosis (MS), and might be accompanied by obstructive-type sleep disorders. To examine this hypothesis, non-smoker and non-obese patients with rheumatic MS and without concomitant diseases were investigated for sleep disorders. METHODS: Patients admitted to the cardiology outpatient clinic at the authors' institution for rheumatic MS during a one-year period were included in the study. Patients were evaluated using the Epworth sleepiness scale, apnea-hypopnea index (AHI), and echocardiographic examination. The relationship between echocardiographic findings and AHI was assessed. RESULTS: Eighteen patients were included in the study. All patients had sinus rhythm and normal electrocardiography recordings, with no coronary artery disease or concomitant cardiac disease. Obstructive sleep apnea (OSA) was determined in 16 patients. AHI was positively correlated with the mean apnea duration, mean gradient, rapid eye movement (REM)-AHI and non-REM-AHI. AHI, pulmonary artery pressure, mitral valve area, mean gradient, left ventricular end-systolic diameter, left ventricular end-diastolic diameter and mean REM-AHI differed significantly according to the degree of MS. AHI was shown to be increased as the degree of MS increased. CONCLUSION: The frequency of OSA was found to be significantly higher in patients with MS. In addition to cardiac problems, these patients need to be evaluated also for sleep problems and treated appropriately. PMID- 26901907 TI - The FORGOTTEN (TRICUSPID) VALVE; THIRD TIME, RIGHT TIME. AB - Tricuspid regurgitation (TR) remains a challenging condition, the indication, timing and type of surgery for which are not yet well established. A 42-year-old woman was referred to the authors' institution with recurrent, symptomatic TR at one year after she had undergone tricuspid valve repair for an Ebstein's anomaly. At 14 months after the first surgery a bioprosthesis was implanted for a detached annuloplasty ring, and she made a complete recovery. However, at 15 months after valve replacement she presented again with right heart failure and massive TR due to rare early pannus formation. A re-redo tricuspid valve replacement was performed. Tricuspid valve replacement with a bioprosthesis is a valid option if repair is unsuccessful. However, there is a need to be aware of concomitant problems such as a requirement for pacemaker implantation, the risk for prosthesis thrombosis or pannus formation, and the importance of anticoagulation therapy. Annual transthoracic echocardiographic follow up is advisable to exclude subclinical TR. PMID- 26901908 TI - Asymptomatic Tricuspid Stenosis Following a Complex Lead Extraction Procedure. AB - The number of transvenous extraction procedures for leads of intracardiac rhythm devices increased recently and the most common reason for lead extraction is device infection. In some cases, combined use of two different techniques is necessary. Long-term results of this approach are not clear. In this case report, we present a patient with biventricular implantable cardioverter defibrillator who underwent percutaneous hardware removal due to recurrent pacemaker pocket infections. Mechanical dilator sheath removal and Needle's Eye Snare were used in the same patient. Although asymptomatic, tricuspid stenosis was detected three years after the operation. PMID- 26901909 TI - Tricuspid Valve Repair with Pericardial Tube Placement via a Right Minithoracotomy. AB - The optimal surgical intervention for tricuspid valve endocarditis remains challenging in the setting of intravenous drug abuse. The situation is often complicated by aggressive bacterial pathogens, an increased risk of reinfection and reoperation, and poor long-term survival, despite a typically younger age at presentation. Herein, the case is presented of a 30-year-old female with infective endocarditis of the tricuspid valve secondary to intravenous drug abuse. The patient underwent minimally invasive tricuspid valve reconstruction utilizing a bovine pericardial tricuspid tube. This is a viable alternative to conventional techniques, and may reduce the risk of reinfection and reoperation, maintain ventriculo-tricuspid integrity, provide structural support, and also be performed via a minimally invasive approach. PMID- 26901910 TI - First Explantation of Direct Flow Medical Transcatheter Valve. AB - Next-generation transcatheter heart valves are designed to overcome procedure related adverse events such as vascular complications and annulus rupture, and to minimize paravalvular regurgitation. The Direct Flow Medical valve is fully repositionable and shows promising results. The case is presented of Direct Flow Medical valve implantation in a patient with a functional bicuspid aortic valve. Multiple repositioning maneuvers failed to overcome the anatomic difficulties, and this resulted in a moderately high persisting gradient and moderate paravalvular leakage. Surgical valve explantation was necessary which, to the present authors' knowledge, is the first such case of Direct Flow Medical valve explantation to be performed. PMID- 26901911 TI - Treatment of Aortic, Mitral and Tricuspid Structural Bioprosthetic Valve Deterioration Using the Valve-in-Valve Technique. AB - BACKGROUND AND AIM OF THE STUDY: The percutaneous approach for a failed bioprosthetic valve is an emerging alternative to redo-valve surgery in patients at high surgical risk. The study aim was to describe the treatment of patients with structural bioprosthetic valve deterioration, using the valve-in-valve technique. METHODS: A total of 33 consecutive patients with symptomatic structural bioprosthetic valve deterioration was treated at the authors' institution, using the valve-in-valve technique. RESULTS: The valve-in-valve procedure in the aortic position was performed in 23 patients (mean age 81.4 +/- 5.9 years; mean STS score 9.6 +/- 5.4). The self-expandable and balloon expandable devices were used in 21 cases (91.3%) and two cases (8.7%), respectively. Procedures were performed via the trans-femoral, trans-axillary and trans-apical routes in 18 (78.2%), three (13%) and two (8.7%) cases, respectively. After the procedure, all patients were in NYHA class I/II. Survival rates were 95.6% at the one-year follow up. The valve-in-valve procedure in the mitral position was performed in 10 patients (mean age 73.6 +/- 15 years; mean STS score 7.7 +/- 4.1). All procedures were performed using the balloon expandable device via the trans-apical route. The composite end point of device success was achieved in all patients. Survival rates were 100% and 75% at one month and two years' follow up, respectively. A single valve-in-valve implantation within a failed tricuspid bioprosthetic valve was also successfully performed. CONCLUSION: In the authors' experience, the valve-in-valve technique for the treatment of a wide range of bioprosthetic valve deterioration modes of failure in different valve positions is safe and very effective. PMID- 26901912 TI - A Case Series of Obstructive Prosthetic Mitral Valve Thrombosis, Successfully Treated with Low-Dose, Slow Infusion Tissue-Type Plasminogen Activator. AB - BACKGROUND AND AIM OF THE STUDY: Prosthetic valve thrombosis (PVT) is a rare but serious complication of the prosthetic heart valve. Although recent guidelines generally recommend surgical treatment as the main option for patients with obstructive left-sided PVT, thrombolytic therapy (TT) may offer another attractive approach. There is also no consensus on the type, dose and route of administration of thrombolytic agents. The present study included a small series of patients with low-dose, slow infusion tissue-type plasminogen activator (tPA) to treat PVT in the mitral position. METHODS: Eight consecutive episodes of mitral PVT (one woman was pregnant) in seven patients were treated with low-dose (25 mg), slow infusion (within 6 h) tPA, if needed, with repeat sessions of TT (with the same protocol up to a total dose of 150 mg) until a satisfactory result was achieved. RESULTS: The cause of PVT was inadequate anticoagulation with warfarin or low-molecular-weight heparin in all patients on admission. A complete resolution of hemodynamic instability and echocardiographic abnormalities was observed in all cases, without mortality. In addition, there were no thromboembolic and major hemorrhagic complications in the case series. CONCLUSION: These findings suggest that low-dose, slow infusion tPA may be applicable to bileaflet mitral PVT in relatively stable patients, and may represent a therapeutic option to surgery. PMID- 26901913 TI - Hemodynamic comparison between Trifecta and Freestyle valves implanted in small aortic roots. One-year echocardiographic results from a prospective randomized study. AB - BACKGROUND AND AIM OF THE STUDY: Aortic valve replacement in patients with a small aortic root may be associated to high residual gradients. In such patients, both stentless valves and aortic annulus enlargement can reduce these residual gradients. Several studies have reported that Trifecta valves yield very good hemodynamic results. The aim of the present study was to compare the hemodynamic performance of Trifecta vs. Freestyle valves at one year in patients with an aortic annulus <= 2.3 cm. METHODS: Between September 2011 and September 2013, 40 patients with a native aortic annulus diameter <= 2.3 cm and average age of 81 +/ 4 years, were randomized to receive either a St-Jude Trifecta stented prosthesis (20 patients) or a Medtronic Freestyle stentless prosthesis (20 patients). RESULTS: No differences between Trifecta and Freestyle were found at one year in mean gradient s: 6.1 +/- 3 mmHg and 6.6 +/- 3 mmHg (p = 0.796); effective ori fice area: 1.82 +/- 0.3 mmHg and 1.76 +/- 0.4 mmHg (p = 0.676) or regression of left ventricular mass: - 25% +/- 14 vs. -19% +/- 16 (p = 0.204), respectively. Only moderate patient -pro sthesis mismatch was found, which affected 3 patient s in each group. CONCLUSION: At one year both stentless and stented prostheses yielded comparable hemodynamic results. These data suggest that Trifecta implantation is a valid means of avoiding patient -prosthesis mismatch in aortic valve replacement in elderly patients with a small native aortic annulus. PMID- 26901914 TI - Ten Years' Experience of Pregnancy Outcomes in Women with Cardiac Valvulopathies: Are Valve Prostheses Worst? AB - BACKGROUND AND AIM OF THE STUDY: The population of pregnant women with valvular heart disease (VHD), and in particular with valvular heart prostheses (VHPs), represents a unique patient group where data are scarce, and where there is an increased risk for adverse maternal and obstetric events. The study aim was to assess the experience of a tertiary center with regards to cardiac and pregnancy outcomes in women with VHD, comparing VHPs with other VHD pathologies. METHODS: A retrospective analysis of 84 pregnancies in women with VHD (mean age 27.5 +/- 5.5 years) was carried out over a 10-year period. Twenty-three pregnancies with VHPs (group A) and 61 with other VHD pathologies (group B) were identified and their cardiac, obstetric, and neonatal outcomes evaluated. RESULTS: At the start of pregnancy, group A included more patients with an impaired left ventricular ejection fraction (LVEF) (15.8% versus 3.9%, p = 0.014), with a previous history of cardiac medication (82.6% versus 29.5%, p = 0.000), and with arrhythmic or ischemic events (18.2% versus 4.9%, p = 0.076). A deterioration in NYHA functional class was the most common cardiac complication (8.3%), and in 7.1% of patients it was necessary to initiate some form of cardiac medication. No maternal deaths were recorded. Group A presented significantly more hemorrhagic and thrombotic complications; all of these events were in women receiving low molecular-weight heparin. There were 95.5% live births, with a medium birth weight of 3068 +/- 498 g. In the VHP group there was also a higher incidence of spontaneous abortion (26.1 versus 3.3, p = 0.005), newborns small for gestational age (30.0 versus 0.4, p = 0.07) and mean Apgar score < 7 (16.7 versus 0.0, p = 0.031). Warfarin embryopathy was observed in one case. CONCLUSION: With the multidisciplinary care provided, pregnancy was relatively well tolerated and successful. However, the presence of a VHP remains a challenging condition that is associated with elevated maternal and fetal morbidity. A worse baseline cardiac status of the mother, as well as anticoagulation issues, were determinants for these findings. PMID- 26901915 TI - Management of Prosthetic Thrombosis During Pregnancy: Importance of a Multidisciplinary Approach. AB - A 40-year-old female of African origin presented in the 32nd week of her second pregnancy with thrombosis of a bileaflet mechanical prosthesis implanted in the mitral position. After an emergency cesarean section, she was successfully treated by means of a multidisciplinary approach. PMID- 26901916 TI - Radical Resection of Cardiac Angiosarcoma with Atrioventricular Reconstruction. AB - Cardiac sarcomas are rare and have a poor prognosis. The details are presented of a patient with a right atrial angiosarcoma who underwent radical resection with reconstruction of the right atrium with a bovine pericardial patch, tricuspid valve replacement, and bypass of the right coronary artery. Survival is improved in patients who successfully undergo total (R0) resection. For this reason, an aggressive approach to resection is recommended, with extensive reconstruction for all patients with cardiac sarcoma. PMID- 26901917 TI - Pulmonary Valvuloplasty by Autologous Pericardium in a Patient with Active Infectious Endocarditis and Osler's Disease. AB - Osler's disease is a rare condition of autosomal dominant inheritance characterized by bleeding and telangiectasia of the skin and mucosal membranes. A few reports exist of open-heart surgery in patients with Osler's disease. Here, the case is presented of a successful pulmonary valvuloplasty using autologous pericardium to treat active infectious endocarditis of the pulmonary valve in a patient with Osler's disease. Such patients are at higher risk of bacteremia because of their chronic nasal bleeding or pulmonary arteriovenous fistula. In patients with Osler's disease, valuvloplasty using autologous pericardium is considered effective for preventing the later recurrence of IE. PMID- 26901918 TI - Effectiveness of Anti-Calcification Technologies in a Rabbit Model. AB - BACKGROUND AND AIM OF STUDY: A kinetic profile revealing calcification progression is a powerful method for assessing the anti-calcification efficacy of various tissue treatments compared to the traditional analysis of a single time point in studies with rabbits. METHODS: Tissue calcification was compared between test and control discs in rabbits. Test groups received either ThermaFix processed bovine pericardium, or porcine leaflets processed with Linx, or alpha amino oleic acid (AOA). Control groups received glutaraldehyde-treated porcine valve leaflets, and bovine pericardium. Tissue discs were implanted intramuscularly in rabbits and explanted every five days until day 75. Levels of calcium and phosphorus were then monitored in the rabbit tissues. RESULTS: Calcium concentrations were plotted over time, with a sigmoidal curve being used for each kinetic profile. The ThermaFix group exhibited a lower calcium plateau level compared to the bovine control (107 +/- 24 versus 258 +/- 120 MUg Ca2+ per mg dry tissue, respectively), while the Linx group exhibited a lower calcium plateau compared to porcine controls (130 +/- 34 MUg versus 280 +/- 80 MUg Ca2+ per mg dry tissue, respectively). The AOA group showed a low level of calcification through 40 days, but this was subsequently increased to a plateau of 258 +/- 135 MUg Ca2+ per mg dry tissue. CONCLUSION: The study results showed that effects on the rate and level of calcification of anti-calcification technologies can be modulated. In particular, time is important when assessing tissue technology effectiveness. PMID- 26901919 TI - Computational Hemodynamic Investigation of Bileaflet and Trileaflet Mechanical Heart Valves. AB - BACKGROUND AND AIM OF THE STUDY: The trileaflet heart valve is a more desirable mechanical heart valve due to its similarity to native heart valves, which produce a central blood flow with decreased blood flow disturbance. There are, however, many challenges and difficulties in designing a trileaflet valve, mainly due to a greater number of moving mechanical parts. METHODS: The flow profiles through a bileaflet mechanical heart valve (BMHV) and a trileaflet mechanical heart valve (TMHV) were compared at downstream regions. Geometric models of a 29 mm St. Jude Medical BMHV and a TMHV were used and positioned at the anatomic position in a curved aortic downstream geometry. Three-dimensional numerical simulations for both types of mechanical heart valve were performed under normal physiological pulsatile flow conditions. Flow profiles were studied under three different implantation locations at Z = 1D (D = 29 mm inlet diameter), 2D and 4D along the aorta centerline during peak systole. RESULTS: The simulation results showed different flow fields at the downstream positions at Z = 1D and 2D. The leaflets of the BMHV obstructed the flow, while the TMHV allowed a central orifice flow which resulted in a more physiological flow profile. Further downstream, at Z = 4D, the flow fields shared similarities in terms of the flow profile and velocity magnitude. CONCLUSION: The findings of this study may help to further improve the development of the TMHV. PMID- 26901920 TI - Quantitative Cardiology: Back to Square One. PMID- 26901921 TI - Resolution from a different perspective. PMID- 26901922 TI - Looking back planning forward. PMID- 26901923 TI - New training standards for Wales' healthcare support workers. PMID- 26901924 TI - Additional L47.6 million health funding to tackle significant pressures. PMID- 26901925 TI - NICE issues new guideline to preserve national stocks of blood. PMID- 26901926 TI - Hospital inpatients care: over 10,000 more admissions a day than 10 years ago. PMID- 26901928 TI - Wrong site surgery: A critical incident analysis of a near miss. AB - This article is a reflective account of a near miss that happened in clinical practice during a particularly busy operating list. This critical incident highlights issues that can arise from a breakdown of communication between members of a multidisciplinary team and demonstrates how ineffective teamwork can jeopardise a patient's safety and wellbeing. It emphasises the effects of human factors on professional performance and how they can contribute to mistakes and misconducts. It also stresses the importance of reporting patient safety incidents so that the lessons can be learned and future practice improved. PMID- 26901927 TI - Constant exposure to the operating theatre can change our perception of the perioperative journey. PMID- 26901929 TI - Coordinating perioperative care for the 'high risk' general surgical patient using risk prediction scoring. AB - Identifying 'high risk' (> 5% mortality score) emergency general surgical patients early, allows appropriate perioperative care to be allocated by securing critical care beds and ensuring the presence of senior surgeons and senior anesthetists intraoperatively. Scoring systems can be used to predict perioperative risk and coordinate resources perioperatively. Currently it is unclear which estimate of risk correlates with current resource deployment. A retrospective study was undertaken assessing the relationship between deployment of perioperative resources: senior surgeon, senior anesthetist and critical care bed. The study concluded that almost all high risk patients with high POSSUM mortality and morbidity scores had a consultant senior surgeon present intraoperatively. Critically unwell patients with higher operative severity and perioperative morbidity scores received higher care (HDU/ICU) beds postoperatively, ensuring that they received appropriate care if their condition deteriorated. Therefore POSSUM scoring should be used perioperatively in emergency cases to coordinate appropriate perioperative care for high risk general surgical patients. PMID- 26901930 TI - Development and efficiency of dedicated upper limb trauma lists in a district general hospital. AB - The aim of this audit was to assess the impact of dedicated upper limb trauma lists on the hospital stay and satisfaction of patients treated operatively for upper limb injuries. In first audit, we reviewed the data of 52 consecutive patients with upper limb injuries treated on the routine trauma lists. Accordingly, a new pathway of dedicated upper limb trauma lists was introduced whereby patients presenting with injuries were safely discharged home with written instructions regarding arrangements for surgery. The audit loop was then closed by collecting data of 78 consecutive patients treated using the new scheme. Dedicated upper limb trauma lists have reduced our in-patient stay without affecting the care and outcomes for our patients. The lists also improved patient satisfaction as arrangements for surgery were more convenient. PMID- 26901931 TI - Wiring of patellar fractures by Joseph Lister. AB - Joseph Lister (1827-1912) was the father of modern surgery and, in particular, of today's orthopaedic surgery. Before Lister, surgeons seldom opened into a joint or performed an open operation for failed reduction or malunion of a fracture. Indeed, most surgical teachers condemned such procedures because of the almost invariable complications of wound suppuration, pyaemia prolonged illness and often death. PMID- 26901932 TI - "Nurses should lead the culture change". PMID- 26901933 TI - Guaranteed work scheme in store for London nurses. PMID- 26901934 TI - Capital's nursing post vacancy rate worsens. PMID- 26901935 TI - Trust matches London wages to retain nurses. PMID- 26901936 TI - Deadline up for replacement of syringe drivers. PMID- 26901937 TI - Slump in district nurse numbers amid overall rise in nursing staff. PMID- 26901938 TI - Placement system 'too fragile' to cope with student increase. PMID- 26901939 TI - Top nurse becomes England's first 'whistleblowing guardian'. PMID- 26901940 TI - Innovative HCA team eliminates falls among dementia inpatients. PMID- 26901941 TI - Alert for airway humidification devices issued. PMID- 26901942 TI - "Maternity care has improved but some areas can still do better". PMID- 26901943 TI - "The modern nurse needs to be capable of improvising". PMID- 26901944 TI - Proud providers of care. PMID- 26901945 TI - "Shared governance has given us the power of collaboration". PMID- 26901946 TI - Practical procedures: oxygen therapy. AB - Knowing when to start patients on oxygen therapy can save lives, but ongoing assessment and evaluation must be carried out to ensure the treatment is safe and effective. This article outlines when oxygen therapy should be used and the procedures to follow. It also describes the delivery methods applicable to different patient groups, along with the appropriate target saturation ranges, and details relevant nurse competencies. PMID- 26901947 TI - A hands-on teaching aid for pressure ulcer prevention. PMID- 26901948 TI - The right to be rude: managing conflict. AB - NHS staff are expected to behave respectfully and courteously to patients, but the same standards of behaviour do not apply to patients. While abusive behaviour is unacceptable from patients, what may be perceived as "rudeness" is often a result of emotions or other factors that may not be obvious. If healthcare staff see such patients as rude, it may negatively affect the care they give. This article discusses what may lie behind "rude" behaviour and presents a model that staff can use to reframe their perceptions of and responses to it to ensure a positive outcome. PMID- 26901949 TI - Using shared governance to empower nurses. AB - Service improvement is a key theme of nurse education and nurses are encouraged to continually improve care outcomes. However, in practice, nurses often lack time and support for continuous improvement. Amid a national shortage of nurses and midwives, as well as high turnovers of staff, shared governance offers a structure in which quality improvement is the main aim and career development is a benefit. This article explains the concept and outlines the benefits and barriers of such a structure. PMID- 26901951 TI - Charity begins ... overseas. PMID- 26901950 TI - 60 seconds with Karen Jackson. PMID- 26901952 TI - BATTLING DEMONS. PMID- 26901953 TI - LEFT WANTING MORE. PMID- 26901954 TI - AUTHOR MATTHEW KUNKLE, EMT-PM, CCP, RESPONDS. PMID- 26901955 TI - SELF ATTRIBUTES. PMID- 26901956 TI - A HOLIDAY HEART. PMID- 26901957 TI - DELAYED DEATH. PMID- 26901958 TI - ALS VS. BLS. PMID- 26901959 TI - CITIZEN RESCUERS. PMID- 26901960 TI - 2015 SALARY SURVEY. PMID- 26901961 TI - REBUILDING EMS IN THE MOTOR CITY. PMID- 26901962 TI - GETTING EMS FIT. PMID- 26901963 TI - BOARD APPROVED RESEARCH. PMID- 26901964 TI - UNNECESSARY CALLS. PMID- 26901965 TI - PEELING BACK THE LAYERS. PMID- 26901966 TI - CARRYING THE WEIGHT. PMID- 26901967 TI - Assisted Living and Nursing. AB - In summary, some Nebraska ALFs are admitting people on Medicaid waivers and people with relatively advanced dementia. They are retaining people on hospice care. Many employ and even advertize that they have RNs, yet regulations prevent these RNs from using their judgment, from practicing professional nursing. This is a total disregard of what RNs, exercising their full scope of professional practice, can bring to a setting, and of what many of the residents in ALFs need. It is time Nebraska ALFs stepped up to meeting the care needs of the residents they admit and retain by providing RN care and oversight to those who need it. They also should provide more than one level of care so that those who only need help with ADLs do not have to pay for a level of care they do not need. Now that there is a group studying the future of AL in Nebraska, is the time to make the changes in regulations--to no longer interfere with professional nurses' legal scope of practice in a setting where they are employed, and to meet the needs of the residents they are admitting and retaining. Other states should do likewise. PMID- 26901968 TI - Continuing Nursing Education and Needs Assessments. PMID- 26901969 TI - MIND THE GAP. HIM RUSHES TO BRIDGE EDUCATIONAL AND PROFESSIONAL GAPS CAUSED BY A QUICKLY ADVANCING INDUSTRY. PMID- 26901970 TI - DISSECTING THE DETAILS. DOCUMENTATION BASED CODING MODEL OFFERS ADVANCED APPROACH TO WORKFORCE CODING TRAINING. PMID- 26901971 TI - Optimizing PHI Disclosure Management in the Age of Compliance. PMID- 26901972 TI - HIM After Retirement. NO NEEDLEPOINT FOR THESE RETIREES, WHO ARE FINDING NEW WAYS TO CONTRIBUTE TO THE PROFESSION ... ON THEIR OWN TERMS. PMID- 26901973 TI - FDA Offers Guidance on Cybersecurity and Medical Devices. PMID- 26901974 TI - Metadata Offers Roadmap to Structured Data. PMID- 26901975 TI - Informatics Education for HIM Professionals in the Era of Interoperable Standards Based HIEs. PMID- 26901976 TI - Evaluating the Information Governance Principles for Healthcare: Accountability and Transparency. PMID- 26901977 TI - Including Patient-Generated Health Data in Electronic Health Records. PMID- 26901978 TI - Hospital Discharge Status Codes: Risks and Rewards. PMID- 26901979 TI - CPT Updates for CY 2015. PMID- 26901980 TI - Privacy or convenience? PMID- 26901981 TI - When medical devices fail: Lessons learned in a hemodialysis unit. AB - Technology and medical equipment devices have become integrated in the delivery of health care. These technologies and devices can introduce new risks, either through user error or malfunction. When these incidents occur, it is important they are reported so that learning and improvements are possible. A just culture encourages reporting of incidents by not blaming individuals, but rather by seeking to understand incidents in relation to how they occurred because of the systems in place. These concepts are explored through a case study in a dialysis unit where a malfunction of a medical equipment device (central venous catheter) was identified. The process for addressing the issue is defined and includes reviewing applicable data, reporting incidents, and evaluating devices that malfunctioned. Finally, the role of the frontline health care professional is identified as an important stakeholder in identifying issues with technology and medical devices, reporting these incidents, and participating in the process that resolves the issues. PMID- 26901982 TI - Delusional parasitosis in patients on dialysis. PMID- 26901983 TI - Early results suggest merits of enhanced recovery after surgery. PMID- 26901984 TI - Managing disruptive behavior will remove bullies from the OR. PMID- 26901985 TI - Lower patient satisfaction associated with nurses educated abroad. PMID- 26901986 TI - Nurse leaders play pivotal role in implementing enhanced recovery programs. PMID- 26901987 TI - Active listening lowers stress, builds confidence. PMID- 26901988 TI - Professional peer review compels staff to improve performance and quality--Part 1. PMID- 26901989 TI - ST to RN program speeds nurse orientation and bolsters perioperative workforce. PMID- 26901990 TI - Combine and conquer: OR/CSPD collaboration dramatically reduces IUSS rates. PMID- 26901991 TI - Fine print in supply contracts often holds keys to cost savings. PMID- 26901992 TI - A Unified Voice Is Needed To Affect Change: Maintenance of Certification in Michigan. PMID- 26901993 TI - Is Maintenance of Certification A Violation of the Antitrust Laws? PMID- 26901994 TI - E-cigarettes: A Physician's Dilemma. PMID- 26901995 TI - What Recourse Do Physicians Have To Express Their Concerns Regarding Meaningful Use? PMID- 26901996 TI - It's Time for Change! Conversations About Maintenance of Certification! PMID- 26901997 TI - Overcoming the Stress of Malpractice Litigation: Solutions to Help Physicians Stay Healthy and Engaged. PMID- 26901998 TI - Five Ways to Get Your Finances In Order In the New Year. PMID- 26901999 TI - Detection of Lymph Nodes Metastasis in Biliary Carcinomas: Morphological Criteria by MDCT and the Clinical Impact of DWI-MRI. AB - BACKGROUND/AIMS: This study was conducted to assess the usefulness of multi-slice CT (MDCT) and diffusion weighted MR images (DWI-MRI) for diagnosis of metastatic lymph nodes (LNs) in biliary carcinomas. METHODOLOGY: Eighteen patients with biliary carcinomas (total 121 LNs) underwent surgical resection were included. In MDCT, the following criteria were measured: the maximum diameter, the enhanced value and the long and short axis (L/S) ratio. In DWI-MRI, the apparent diffusion coefficients (ADCs) were measured from ADC maps. RESULTS: In ROC analysis, the maximum diameter has the highest diagnostic power with area under curves of 0.903. And when the maximum diameter 8 mm and L/S ratio is less than 2, the accuracy was improved with a sensitivity of 81%, positive predictive value (PPV) of 45%. In DWI-MRI, ADCs values of metastatic LNs significantly lower than that of non-metastatic LNs (mean: 1.65 vs. 2.11 x10 3mm2/s). When the ADC value of 1.8 x10(-3) was used as a cut-off value, the best results were obtained with sensitivity of 75%, PPV of 82%. CONCLUSIONS: Using MDCT, diagnosis of LNs metastasis should be more than 8mm diameter and less than 2 of L/S ratio. In addition, DWI-MRI is more useful modality for diagnosis of LNs metastasis. PMID- 26902000 TI - Utility of Intraductal Ultrasonography as a Diagnostic Tool in Patients with Early Distal Cholangiocarcinoma. AB - BACKGROUND/AIMS: It is difficult to diagnose cholangiocarcinoma in the early stages because most patients present with jaundice, which is generally thought to be the most important symptom at diagnosis. Despite improvements to surgical instruments and techniques, these rates are not quite satisfactory. Intraductal ultrasound (IDUS) is easy to handle due to the wire-guided, thin-caliber, and high-frequency probe. The purpose of the present study was to assess the efficacy of IDUS as a diagnostic tool for patients with early distal cholangiocarcinoma. METHODOLOGY: We enrolled 23 with early distal cholangiocarcinoma. The cholangiography and IDUS findings were retrospectively analyzed. The morphology of the tumors detected by IDUS was also classified including localized wall thickening, polypoid lesion, and sessile tumor. RESULTS: The morphologies on IDUS were as follows: five (21.7%) localized wall thickenings, five (21.7%) polypoid lesions, and 13 (56.5%) sessile tumors. CONCLUSIONS: Since forceps biopsy complemented by IDUS can substantially improve the diagnostic rate, pathological investigations should be performed simultaneously after detection by IDUS. We believe that noninvasive modalities should be followed by IDUS and used as a decisive approach to distinguish between benign and malignant status. PMID- 26902001 TI - Predictive Factors for NSAIDs-related Gastrointestinal Toxicity: Can COX-2 Selective Inhibtor Prevent it?. AB - BACKGROUND/AIMS: To identify predictive factors for NSAIDs-related GI toxicity and to clarify whether cox-2 selective inhibitors can prevent it or not. METHODOLOGY: We have surveyed all patients received esophagogastroduodenoscopy examined at our hospital between January 2008 and September 2011. We performed the following retrospective analyses of the clinical records of the 253 patients prescribed NSAIDs. The severity of gastro duodenal mucosal lesions was evaluated using the modified gastro duodenal LANZA score. The following scores for response were used: 0 = no lesions (LANZA score 0); 1 = erosion and redness (LANZA score 1 3); 2 = ulcer (LANZA score 4). Predictors evaluated were factors potentially related to pathogenesis of NSAIDs related GI toxicity. Ordered logistic regression analysis was performed to identify predictive factors for NSAIDs related. ulcer. RESULTS: A multivariate logistic regression identified number of risk factors (odds ratio (OR) = 6.82, confidence interval (CI) = 5.31-8.76; P = 0.01), concomitant use of anti- cancer drugs (OR = 2.17, Cl = 1.02-4.62; P = 0.04) were found to be significant factors. CONCLUSIONS: Number of risk factors and concomitant use of anticancer drugs were shown to be predictive factors for NSAID-related GI toxicity. Use of celecoxib or proton pump inhibitor was not identified as a protective factor. PMID- 26902002 TI - Risk Factors Associated with Intraoperative Major Blood Loss during Resection of Hepatocellular Carcinoma. AB - BACKGROUND/AIMS: Intraoperative blood loss is an independent predictor of recurrence and survival after resection of hepatocellular carcinoma (HCC). The aim of this study was to identify the risk factors associated with intraoperative major blood loss in patients undergoing liver resection for HCC. METHODOLOGY: Clinicopathologic data and perioperative outcomes of 386 patients who underwent liver resection for HCC were retrospectively reviewed. The patients were divided into high (> 1,000 mL) and low (51,000 mL) blood loss groups according to the intraoperative blood loss. Intraoperative blood loss,more than 1,000 mL was defined as major blood loss. The risk factors associated with intraoperative major blood loss were analyzed by univariate and multivariate analyses. RESULTS: Vascular invasion, major hepatectomy and prolonged operation time were risk factors associated with intraoperative major blood loss during resection of HCC on multivariate analysis. Moreover, HCC patients with intraoperative major blood loss had prolonged hospital stay, higher incidence of postoperative complication and mortality compared with patients' with blood loss 1,000 mL. CONCLUSIONS: Vascular invasion, major hepatectomy and prolonged operation time are independent predictors of intraoperative major blood loss during resection of HCC. PMID- 26902003 TI - Bypass Operation as Palliation for Unresectable Esophageal Cancer: Selection of Suitable Patients. AB - We evaluated the bypass operation as palliation for unresectable esophageal cancer. In this study, patients were divided into 2 groups. Group A included 19 patients with good progress, defined as sufficient oral ingestion for more than 2 months. The other 10 patients were in Group B and had poor progress. Oral ingestion was impossible postoperatively in 2 of 29 cases. Although there is a difference of a grade, other patients could have improvement of quality of life. Patients with no preoperative therapy and patients whose nutrient state was maintained comparatively well had a good adaptation after bypass surgery. We concluded that if the surgeon chooses the patients carefully, bypass is a very useful operative method. PMID- 26902004 TI - Bevacizumab Combined with Chemotherapy as First-line Therapy for Advanced Non Small Cell Lung Cancer: A Retrospective Study. AB - BACKGROUND/AIMS: This study was designed to investigate the effect of bevacizumab plus chemotherapy such as pemetrexed and carboplatin followed by maintenance bevacizumab in patients with advanced, nonsquamous nonsmall cell lung cancer. METHODOLOGY: Previously untreated patients with advanced, non-squamous nonsmall cell lung cancer received bevacizumab 15 mg/kg, pemetrexed 500 mg/m2 and carboplatin atan area under the concentration-time curve of 6 intravenously on day 1 every 21 days. Responding or stable patients who completed 6 cycles then received bevacizumab maintenance every 21 days until disease progression. In total, 32 patients were entered on the study. RESULTS: No complete responses were observed, and 16 patients (50%) had a partial response. Sixteen patients (50%) displayed disease stability. The progression-free survival was 11.92 +/- 6.12 months, and the overall survival was 12.52 +/- 5.56 months. Treatment-related grade adverse events were obsearved gastrointestinal reaction (68%), rash (2%), Pectoralgia (1%), headache (1%), rlopecia (1%), renal function (1%), liver function (1%), and diarrhea (1%). CONCLUSIONS: Combined pemetrexed, and carboplatin followed by maintenance bevacizumab was well tolerated and displayed remarkable effect in patients with advanced, nonsquamous nonsmall cell lung cancer. PMID- 26902005 TI - Circulating Hepatocellular Cells are a Bad Prognostic Factor for HCC Patients. AB - BACKGROUND/AIMS: Circulating hepatocellular carcinoma cells (CHCCs) may be detected by reverse transcription-polymerase chain reaction (RT-PCR). We investigated the relationship between CHCCs and hepatoma patients' survival period after different managements. METHODOLOGY: Peripheral blood (5 ml) samples were obtained from 93 patients with hepatocellular carcinoma (HCC), and from 33 control subjects (9 with liver cirrhosis after hepatitis B, 14 with chronic hepatitis B, 10 with healthy people) between January 1st, 2009 and December 31, 2012. To detect CHCCs in peripheral blood, alpha-fetoprotein (AFP) messenger RNA (mRNA) was amplified from total RNA extracted from whole blood by RT-PCR. RESULTS: AFPmRNA was detected in 49 blood samples from the HCC patients (49/93, 53.0%). In contrast, there were no clinical control subjects whose samples showed detectable AFPmRNA. The presence of AFPmRNA in blood seemed to be correlated with the tumor stage (by TNM classification) of HCC, the serum AFP value, and the presence of intrahepatic metastasis, portal vein thrombosis, tumor diameter and/or distant metastasis. CONCLUSIONS: The presence of AFP mRNA in peripheral blood may be an indicator of CHCCs, which might predict hematogenous spreading metastasis in patients with HCC and may be as a bad prognostic factor for HCC patients. PMID- 26902006 TI - The Clinical Effects of Dai-kenchu-to on Postoperative Intestinal Movement and Inflammatory Reaction in Colorectal Surgery. AB - BACKGROUND/AIMS: We analyzed the effects of the Kampo medicine "Dai-kenchu-to" (DKT) on clinical aspects in colorectal surgery. METHODOLOGY: Total 122 patients who underwent colorectal cancer surgery were divided into a DKT group (n = 53) and a non-DKT group (n = 69). The differences of postoperative course and anti inflammatory responses between those two groups were analyzed. RESULTS: The 53 out of 59 patients could completely take DKT. In the postoperative course, significant difference was observed in the first flatus day. In the anti inflammatory effects, differences were observed in the heart rate (HR) of the 3rd POD. In the change between 1st POD and 3rd POD, HR in the DKT group was well controlled compared to the non-DKT group. In the patients who had over 37.5 degrees C of body temperature in 1st POD (n = 53), inflammatory response of the DKT group was reduced compared to the non-DKT group. CONCLUSIONS: The DKT might have the favorable influences on postoperative bowel movement and systemic inflammatory reaction, and induce the better postoperative course. PMID- 26902007 TI - Infiltration of Local Anesthesia at Wound Site after Single-Incision Laparoscopic Colectomy Reduces Postoperative Pain and Analgesic Usage. AB - BACKGROUND/AIMS: Minimally invasive laparoscopy provides faster recovery, less pain, fewer complications, and better cosmesis than laparotomy. We aimed to evaluate outcomes of postoperative local anesthesia infiltration at the single incision laparoscopic surgery (SILS) wound. METHODOLOGY: This prospective, non randomized controlled study evaluated outcomes of 58 colorectal cancer cases receiving SILS from May 2010 to December 2010. Twenty-nine patients received postoperative infiltration of local anesthesia at the wound site; another 29 patients did not. Demographic, intra- and postoperative data were compared. Postoperative pain was assessed by visual analogue scale and analgesic usage. RESULTS: Local anesthesia group included 16 males, 13 females (mean age, 62.0 +/- 15.1 years); no local anesthesia group included 14 males, 15 females (mean age, 58.1 +/- 12.7 years). There were no significant differences between groups at baseline (i.e., age, gender, disease stage, tumor location or size) except BMI (25.2 +/- 2.8 vs. 23.5 +/- 3.4, p = 0.041) was significantly higher. Postoperative pain scores were significantly lower in local anesthesia group than in no local anesthesia group (median VAS score 2.0, IQR 2.0-3.0 vs. VAS score 3.0, IQR 3.0-4.0, respectively, P = 0.024). CONCLUSIONS: Our results provide further evidence of SILS safety. Local anesthesia infiltration at SILS wounds decreases postoperative wound pain and analgesic usage. PMID- 26902008 TI - Advancement of Buried Muco- Subcutaneous Sutures for Ostomy Creation in Surgery for Ulcerative Colitis. AB - BACKGROUND/AIMS: Ostomy creation is a fundamental technique. However, little information is available concerning the procedure and the associated complications. We reviewed the relationship between the ostomy procedure and complications. METHODOLOGY: The records of patients who were diagnosed with ulcerative colitis and underwent ostomy creation between January 2007 and July 2012 were reviewed. Stoma complications, including muco-cutaneous dehiscence, fistula and granulation were also reviewed. RESULTS: The study included 176 patients who received interrupted sutures with removal of the stitches and 202 patients who received subcutaneous sutures without removal of the stitches. Among the patients with buried sutures, 108 received braided absorbable sutures and 94 received with mono filament absorbable sutures. The incidence of dehiscence was significantly higher with the interrupted sutures (43.2%) than with the buried sutures (31.2%), although the granulation and fistula rates were not significantly different. Among the patients with buried sutures, fistula (6.4%) and granulation (21.3%) rates were slightly increased with the mono filament sutures compared with the braided sutures, although the differences were not significant. CONCLUSIONS. Suture removal appeared to be an unnecessary manipulation at ostomy creation. Further study for all colorectal surgery is needed to investigate whether the incidence of fistula increases with buried sutures. PMID- 26902009 TI - Factors Predicting Subsequent Hospitalization in Patients with Ulcerative Colitis: Total Colonoscopic Findings are the Strongest Predictor. AB - BACKGROUND/AIMS: Patients with ulcerative colitis suffer from long term impairment of quality of life, especially when subjected to repeated hospitalization. We aimed to identify factors that may predict future hospitalization. METHODOLOGY: We followed 139 consecutive patients with ulcerative colitis for average of 11.2 years (2.8 to 49.5 years) from the onset. Clinical and endoscopic stagings were determined by Japanese staging system, the extent of colitis by Montreal classification and endoscopic grading by Matts' grade. RESULTS: Overall hospitalization rate was 37% at 5 years, 47% at 10 years and 60% at 20 years from the onset. Of 5 parameters including demographic and staging scores, univariate analysis revealed clinical severity at onset (p = 0.003), total colonoscopic findings on severity (Matts' grade, p = 0.003), and total colonoscopic findings on sites of abnormality (p = 0.012) were significantly correlated with hospitalization. By multivariate analysis, total colonoscopic findings on sites of abnormality was the only baseline character significantly related to the need of hospitalization (p = 0.0007). In fact, 5/10/20 years hospitalization rates were only 18/26/33 percent for proctitis type, whereas those were 61/72/90 for total colitis type. CONCLUSIONS: The total colonoscopic finding on sites of abnormality at the onset is the only predictdr of hospitalization in patients with ulcerative colitis. PMID- 26902010 TI - Serum Type IV Collagen Concentration Correlates with Indocyanine Green Retention Rate. AB - BACKGROUND/AIMS: Assessment of oxaliplatin-associated hepatotoxicity in patients receiving oxaliplatin, fluorouracil and leucovorin chemotherapy (FOLFOX) for colorectal cancer remains controversial. The aims of this study were to clarify which variables are indicators of such hepatotoxicity. METHODOLOGY: Twenty-seven patients who were to receive FOLFOX for colorectal cancer were included in this study. A range of liver function tests, including serum hyaluronic acid (HA) and type IV collagen concentrations, indocyanine green (ICG) retention rate at 15 min (ICGR15) and splenic volume were assessed before commencement of chemotherapy and after four cycles of FOLFOX. RESULTS: No significant changes were found in conventional liver function tests or splenic volume. Significant changes pre- and post-FOLFOX were found in type IV collagen concentrations and ICGR15. Correlation analyses showed that the following two factors were associated with significant changes in ICGR15 after four cycles of FOLFOX: platelet count (p = 0.028, correlation coefficient 0.423), and type IV collagen concentration (p < 0.001, correlation coefficient 0.830). The regression line between type IV collagen concentration and ICGR15 was Y = 2.70 + 0.84 x X. CONCLUSION: Serum type IV collagen concentration is an indicator of oxaliplatin-associated hepatotoxicity and correlates with significant changes in ICGR15 in patients receiving FOLFOX. PMID- 26902011 TI - Anti-TNF-A Therapy about Infliximab and Adalimamab for the Effectiveness in Ulcerative Colitis Compared with Conventional Therapy: A Meta-Analysis. AB - BACKGROUND/AIMS: TNF-alpha has an important role in the pathogenesis of ulcerative colitis (UC). It seems that anti-TNF-alpha therapy is beneficial in the treatment of UC. The aim was to assess the effectiveness of Infliximab and Adalimamab with UC compared with con- ventional therapy. METHODOLOGY: The Pubmed and Embase databases were searched for studies investigating the efficacy of infliximab and adalimumab on UC. RESULTS: Infliximab had a statistically significant effects in induction of clinical response (RR = 1.67; 95% CI 1.12 to 2.50) of UC compared with conventional therapy, but those had not a statistically significant effects in clinical remission (RR = 1.63; 95% CI 0.84 to 3.18) and reduction of colectomy rate (RR = 0.54; 95% CI 0.26 to 1.12) of UC. And adalimumab had a statistically significant effects in induction of clinical remission (RR =1.82; 95% CI 1.24 to 2.67) and clinical response (RR =1.36; 95% CI 1.13 to 1.64) of UC compared with conventional therapy. CONCLUSION: Our meta analyses suggested that Infliximab had a statistically significant effects in induction of clinical response of UC compared with conventional therapy and adalimumab had a statistically significant effects in induction of clinical remission and clinical response of UC compared with conventional therapy. PMID- 26902012 TI - Synchronous and Metachronous Colorectal Cancers: Distinct Disease Entities or Different Disease Courses? AB - BACKGROUND/AIMS: This study aimed to investigate the clinicopathological characteristics of synchronous and metachronous colorectal cancers (CRCs). METHODOLOGY: From January 1, 2001 to December 31, 2010, 5898 patients who underwent surgical resection for CRCs were enrolled. Synchronous CRC was defined as presence of more than one primary CRC within 6 months of resection of the primary tumor; while CRC that occurred at least 6 months later was regarded as metachronous CRC. RESULTS: 5346 patients were eligible for the study and divided into three groups: solitary, synchronous and metachronous CRC. The overall prevalence of the synchronous CRC was 2.2% and the 10-year cumulative incidence of metachronous cancer was 0.84%. 29 (64%) metachronous cancers were diagnosed within 3 years of the index cancer and the mean time interval was 3.2 years. Male gender and presence of associated adenoma were significant risk factors for both synchronous and metachronous CRC. Synchronous and metachronous CRC patients shared similar clinicopathological features except that the former were older than the latter by 3.7 years. The five-year survival rates were not different among the three groups. CONCLUSIONS: Our study indicates that synchronous and metachronous CRC might represent similar disease entity with different courses. PMID- 26902013 TI - Development of a Novel Endoscopic Manipulation System: The Endoscopic Operation Robot ver. 2. AB - BACKGROUND/AIMS: The Endoscopic Operation Robot (EOR) ver. 1 was developed in order to provide robotized operational support for flexible endoscopes, which can be complicated to manipulate. However, total colonoscopy examinations with a colonoscopy training model by proficient operation of the joystick using the EOR ver. 1 took about 6 times longer to reach the cecum than with current manual operation. Thus, EOR ver. 2 is a newly developed robot. METHODOLOGY: The time required total colonoscopy examinations with a colonoscopy training model was performed compared using the EOR ver. 1 and using the EOR ver. 2. RESULTS: The median insertion time (in minutes) was 17.20 +/- 3.92 in the EOR ver. 1 group and 9.30 +/- 2.13 in the EOR ver. 2 group (p < 0.05). CONCLUSION: The study suggested the possibility of the clinical application Of the EOR. PMID- 26902014 TI - Simultaneous Laparoscopic Resection of Primary Tumor and Liver Metastases for Colorectal Cancer: Surgical Technique and Short-Term Outcome. AB - BACKGROUND/AIMS: Laparoscopic approaches are increasingly used in selected patients with either colorectal or liver disease. The aim of this study was to evaluate the safety and feasibility of laparoscopy-assisted combined colorectal and liver resection for primary colorectal cancer (CRC) with synchronous liver metastases. METHODOLOGY: Thirteen patients with CRC with synchronous liver metastases who underwent simultaneous laparoscopic colectomy and hepatic resection from January 2009 through July 2013 were evaluated. RESULTS: The patients' median age was 65 years and the median body mass index was 23.7 kg/M2. The primary sites were the right colon in 4 cases, left colon in 6, and rectum in 3. Liver resections consisted of 14 partial resections or 3 left lateral hepatectomies. One patient was converted to open hepatectomy. The median surgical time was 616 (range, 200-907) min, and the median estimated blood loss was 520 (range, 70-2016) mL. Postoperative mortality did not occur. Three patients experienced minor postoperative complications: bile leakage and wound infection. The median hospital stay was 14 (range, 9-58) days. CONCLUSIONS: This study shows that combined colon and liver resection with the laparoscopic approach is technically feasible and safe in selected patients with primary CRC and synchronous liver metastases. PMID- 26902015 TI - Clinical Characteristics and Postoperative Complications of Patients Undergoing Emergency Surgery for Ulcerative Colitis. AB - BACKGROUND/AIMS: Despite recent advances in medical therapy, the role of surgery for severe ulcerative colitis remains important and determining the timing and indications for colectomy are difficult for both gastroenterologists and surgeons. We compared the clinical characteristics and postoperative complications of emergency surgeries for ulcerative colitis to those of elective surgeries. METHODOLOGY: We retrospectively examined 77 patients with ulcerative colitis who underwent colectomy without cancer or dysplasia in our institute in 1989-2012. Clinicopathological features, cytomegalovirus involvement, and postoperative complications were evaluated. RESULTS: Twenty-seven patients underwent emergency surgeries and the other 50 underwent elective surgeries. Emergency surgeries were performed significantly earlier in the disease course than elective surgeries. Postoperative complications were more frequent in emergency surgeries than in elective surgeries. Those who underwent emergency surgeries with relative indications tended to develop postoperative complications more frequently when intensive long-term steroid therapy was introduced. CONCLUSIONS: Emergency surgeries were associated with frequent postoperative complications. For refractory severe ulcerative colitis, cytomegalovirus involvement should be determined and prolonged steroid therapy is associated with postoperative complications; therefore, early treatment decisions are important. PMID- 26902016 TI - New Prognostic Indicator is Useful for Predicting the Survival of Patients with Unresectable Advanced Colorectal Cancer. AB - BACKGROUND/AIMS: Complete resection of tumors is possible after heavy chemotherapy in a few patients with unresectable colorectal cancer (UCRC). This study evaluated the ability of new prognostic score to identify such patients. METHODOLOGY: Four peripheral blood markers were evaluated in 50 patients diagnosed with UCRC at the time of patients' first visit to the hospital: C reactive protein (CRP), albumin (ALB), neutrophil/lymphocyte ratio (NLR), and carcinoembryonic antigen (CEA). Each was scored +1 or 0 for that marker. For example, when patient shows CRP >= 1.0 mg/dL, ALB 3.5 g/dL, NLR >= 5, and CEA >= 10 ng/mL, his score is +4. Thus, patients' scores could range from 0 to +4. RESULTS: The median survival time (MST) of the 15 patients with scores 0 and +1 was longer than that of the 35 with scores +2, +3, and +4 (35 vs. 6 months, P < 0.001). R0 operation after treatment was performed in 2 patients (4%) with score 0 and +1. CONCLUSION: Our prognostic score is useful in selecting patients with UCRC who will survive. PMID- 26902017 TI - Transanal Minimally Invasive Surgery (TAMIS) for Rectal Lesions: A Systematic Review. AB - BACKGROUND/AIMS: Transanal minimally invasive surgery (TAMIS) has received attention as an alternative to transanal endoscopic microsurgery for rectal lesions. We review the effectiveness and safety of TAMIS for the treatment of rectal lesions. METHODOLOGY: The MEDLINE, Web of Science, and Cochrane Library databases were searched using predefined inclusion criteria. The primary outcomes were positive margin rate, recurrence rate, conversion rate, range of applications, and complication rates. To derive pooled estimates of proportions with 95% Confidence Interval (CI) for the outcomes, a random effect model was used. RESULTS: Twelve studies including 155 patients were identified. The weighted mean size of rectal lesions was 3.3 cm (range 0.2-10 cm) and the weighted mean distance from the anal verge was 7.4 cm (range 0-20 cm). Six studies enrolled only the patients with low and mid rectal lesions mainly to avoid peritoneal entrance during excision. CONCLUSIONS: Based on the evidence from this limited number of studies, TAMIS appears to be an effective and safe treatment for rec tal lesions. However, the clinical outcome of TAMIS according to the location of the rectal lesions needs to be clarified. Comparison with other established surgical treatments are also mandatory. PMID- 26902018 TI - Evaluation of Preoperative Chemotherapy with Modified OPTIMOX-1 Plus Bevacizumab in Patients with Advanced Rectal Cancer with Factors Contraindicative of Curative Surgery. AB - BACKGROUND/AIMS: The efficacy and safety of neoadjuvant chemotherapy in patients with highly advanced rectal cancer for whom radical surgery was considered difficult were evaluated. METHODOLOGY: From June 2007 to February 2011, 10 advanced lower rectal cancer patients with factors contraindicative of curative surgery with total mesenteric excision were eligible for this study. Neoadjuvant chemotherapy consisting of modified OPTIMOX1 (mFOLFOX6 and sLV5FU2 alternating administration) plus bevacizumab was administered. RESULTS: Adverse events seen with chemotherapy consisted of grade 2 leukopenia in 1 patient, but there were no cases of delayed administration or dosage reduction due to grade 2 neurotoxicity. The surgical procedures were anus-preserving resection in 8 patients, total pelvic exenteration in 1 patient, and posterior pelvic exenteration in 1 patient. A positive radial margin was confirmed in 3 patients, but radical surgery was performed, histologically as well, in the other patients. Upon comparing the clinical and postoperative histological stages, primary tumor and node downstaging was achieved in 20.0% and 70.0% of the patients, respectively. CONCLUSIONS: These findings suggest the potential utility of neoadjuvant chemotherapy consisting of modified OPTIMOX1 plus bevacizumab prior to permitting radical resection or anus-preserving surgery in patients with highly advanced rectal cancer. PMID- 26902019 TI - Feasibility of Reduced Port Laparoscopic Colectomy for Colon Cancer. AB - BACKGROUND/AIMS: Reduced port laparoscopic surgery has recently emerged as a method to improve the cosmetic results of conventional laparoscopic surgery. We reported our technique of reduced port laparoscopic colectomy using 3-port and short-time outcomes. METHODOLOGY: Between 2005 and 2012, we performed 161 reduced port laparoscopic colectomies using the 3-port technique. Data analyzed in-cluded age, gender, body mass index (BMI), duration of surgery, number of harvested lymph nodes, and duration of hospital stay. RESULTS: All of the cases were successfully performed using the 3-port procedure. The median durations of surgery and postoperative hospital stay were 140 mm (range 75-463 mm) and 9 days (range 5-38 days), respectively. No mortality was associated with this technique. CONCLUSION: Reduced port laparoscopic colectomy is feasible and may have advantages over conventional laparoscopic colectomy. PMID- 26902020 TI - Primary Tumor Resection Offers Higher Survival Advantage in KRAS Mutant Metastatic Colorectal Cancer Patients. AB - BACKGROUND/AIMS: Colorectal cancer is the fourth most common cancer diagnosed in the United States, and the third most common cause of death from cancer. Approximately 20% of the patients with colorectal cancer have distant metastasis during diagnosis. Primary tumor resection is controversial in unresectable metastatic colorectal cancer (CRC). We studied the survival effect of primary tumor resection in unresectable metastatic CRC according to kirsten ras (KRAS) mutation status. METHODOLOGY: Seventy eight CRC cases with unresectable metastasis were included in the study. The KRAS status was known in all patients. 34 patients had undergone primary tumor resection before 1st chemotherapy. RESULTS: ThE median time from primary tumor resection to first chemotherapy was 6 (3-17) weeks. The survival was better in the unresectable metastatic colon patients with resected primary tumor, but it was statistically non-significant (P = 0.07). The median OS was similar (P = 0.91) in the KRAS wild patients with or without primary tumor resection. The median OS was 28 months in KRAS mutant patients with primary tumor resection, 14 months in KRAS mutant patients without primary tumor resection (P = 0.002). CONCLUSION: Primary tumor resection offers survival advantage in KRAS mutant patients, but randomized prospective studies are required. PMID- 26902021 TI - Rapamycin-Mediated mTOR Inhibition Reverses Drug Resistance to Adriamycin in Colon Cancer Cells. AB - BACKGROUND/AIMS: To detect the cellular sensitivity to adriamycin (ADR) by assessing autophagy, apoptosis, and multidrug resistance gene 1 (mdr1) expression in LoVo/Adr cells. METHODOLOGY: LoVo/Adr cells were designated accordingly into ADR group, Rapamycin (RAPA) group, ADR plus RAPA, and control group in main observations. Autophage, cell death and mdr1 were examined. RESULTS: IC50 value of ADR in LoVo/Adr was significantly decreased in response to RAPA (P < 0.05). Autophagy rate of LoVo/Adr cells was higher in the ADR or RAPA-alone group than in control (p < 0.05), while ADR/RAPA combination has significantly increased autophagy rate compared to ADR or RAPA alone (p < 0.05). Compared with controls, apoptosis rate in the RAPA group had no difference (p > 0.05); whereas there was significant difference in ADR group (p < 0.05). Furthermore, apoptosis rate was significantly different in combined RAPA/ADR compared to ADR (p < 0.05). Expression of mRNA and protein P-gp level of mdr 1 gene in LoVo/Adr cells were significantly decreased under RAPA-treated groups at 25 umol/L and 50 umol/L (p < 0.05). CONCLUSION: This study has indicated that the inhibition of the mTOR pathway reverses multidrug resistance in colorectal cancer cells, which is associated with increased autophagy, apoptosis and reduced mdr1 gene expression in drug-resistant cells treated with Adriamycin. PMID- 26902022 TI - Planned Esophagectomy after Neoadjuvant Hyperthermo-Chemoradiotherapy using Weekly Low-Dose Docetaxel and Hyperthermia for Advanced Esophageal Carcinomas. AB - BACKGROUND/AIMS: The optimal treatment for locally advanced esophageal carcinoma has not yet been determined. We report results of neoadjuvant hyperthermo chemoradiotherapy (HCRT) using weekly low-dose docetaxel followed by surgery in patients with advanced esophageal squamous cell carcinoma. METHODOLOGY: Twenty four patients were enrolled. 7 patients were considered to have inoperable tumors or rejected surgery after HCRT, and the remaining 17 patients had an esophagectomy. Clinical responses, HCRT toxicity and survival after surgery were evaluated. RESULTS: In the 24 patients, the response rate was 41.7%. The pathological complete response (pCR) rate was 17.6% in the 17 patients. HCRT toxicity grade 2 occurred in six patients (25.0%: esophagitis, 4; leukopenia, 6; neutropenia, 4) and grade 3 (pneumonia) in 3 patients (12.5%). The 3- and 5-year survival rates were 56.3% and 50.0%, respectively. When the patients were divided into a pCR group and a pathological partial response (pPR) group, the 3-year survival rates were 66.7% and 42.9% and the 5-year survival rates were 66.7% and 42.9%, respectively (log-rank P = .5842). CONCLUSIONS: Esophagectomy after docetaxel HCRT may have potential for prolonging survival in patients with locally advanced esophageal cancer. A larger randomized, controlled study will be required to confirm the benefit of esophagectomy after HCRT. PMID- 26902023 TI - Incidence and Risk Factors for Anastomotic Stricture after Esophagectomy with Gastric Tube Reconstruction. AB - BACKGROUND/AIMS: The aim of this study was to investigate the incidence and risk factors for anastomotic stricture after esophagectomy with gastric tube reconstruction. METHODOLOGY: A total of 150 consecutive patients with esophageal cancer who underwent esophagectomy with gastric tube reconstruction were analyzed in this study. Anastomotic stricture was de fined as disturbance of the passage of a standard endo scope, with no evidence of locoregional cancer recurrence. Cumulative incidence was calculated using the Kaplan-Meier method. A total of 38 clinicopathological variables were assessed to elucidate the risk factors by univariate and multivariate analyses. RESULTS: Anastomotic stricture developed in 61 of 150 patients 41%). The cumulative incidences were 34.2% at 6 months, and 37.9% at 12 months. Fifty-seven patients (93%) developed anastomotic stricture within 12 months after esophagectomy. A low preoperative partial pressure of arterial oxygen (odds ratio, 2.23; 95% confidence interval, 1.10-4.55; p = 0.027) and the presence of postoperative complications of Grade 3 or higher (3.05; 1.04 9.00; p = 0.043) were identified as the independent risk factors. CONCLUSIONS: The incidence of anastomotic stricture after esophagectomy was high. A modification of anastomotic procedure may be necessary for patients with a low preoperative partial pressure of arterial oxygen to prevent the development of stricture. PMID- 26902025 TI - Second-Line Modified FOLFOX6 Regimen in The Patients with Metastatic Esophagus Cancer. AB - BACKGROUND/AIMS: We aimed to investigate the efficacy of second line treatment with modified FOLFOX6 (mFOLFOX6) following cisplatin- plus 5-fluorourasil (CF) chemotherapy in patients with metastatic esophagus cancer (mEC). METHODOLOGY: In our oncology clinic, between March 2011 and September 2014, we reviewed patients admitted with progressive mEC following first line CF chemotherapy and those with >60 kanofsky performance status performed second line mFOLFOX6 regimen. RESULTS: A total of 242 patients with mEC were evaluated. 94 of 242 patients (38.8%) had received second-line chemotherapy treatment. All of these patients had received mFOLFOX6 regime. Median age was 53 years (range: 28-71). The received median number of chemotherapy cycles was 6 (2-12). Objective response rate (ORR) was obtained in 39 of 94 (41.4%) patients, 6 (6.3%) of these had complete response (CR) and 33 (35.1%) had partial response (PR). Stable disease (SD) was obtained in 20 (21.3%) patients and progression was observed in 35 (37.3%) patients. Grade 3/4 toxicity was observed in 67 (71.2%) patients. The hematologic toxicity was found as the most common toxicity (69.1%). CONCLUSIONS: mFOLFOX6 regimen as a second line treatment can be applied to the mEC patients with progressive disease following CF chemotherapy. PMID- 26902024 TI - Usefulness of 18f-Fluorodeoxyglucose Positron Emission Tomography for Predicting the Pathological Response of Neoadjuvant Chemoradiotherapy for T4 Esophageal Squamous Cell Carcinoma. AB - BACKGROUND/AIMS: The purpose of this study is to assess the efficacy of 18F fluorodeoxyglucose (FDG)-positron emission tomography (PET) in predicting the pathological response of neoadjuvant chemoradiation (CRT) for clinically diagnosed T4 esophageal squamous cell carcinoma (SCC). METHODOLOGY: We examined 32 patients with T4 thoracic esophageal SCC who received neoadjuvant CRT followed by surgery. RESULTS: Pathological complete response (pCR) was achieved in 7 patients (21.9%). pCR was significant correlated with standardized uptake value (SUV) after neoadjuvant CRT (P = 0.034) and SUV decrease (%) (P = 0.030). The optimal cut-off values to predict pCR were 2.25 for SUV after neoadjuvant CRT and 79.3 for SUV decrease (%). Of note, no patients who did not reach both cut-off values achieved pCR. Conclusions: SUV after CRT and SUV decrease (%) in FDG-PET of the primary tumor are useful tools to predict pathological response of neoadjuvant CRT for T4 esophageal SCC. PMID- 26902026 TI - Risk Factors Associated with Mortality and Increased Drug Costs in Nonvariceal Upper Gastrointestinal Bleeding. AB - BACKGROUND/AIMS: To determine risk factors associated with mortality and increased drug costs in patients with nonvariceal upper gastrointestinal bleeding. METHODOLOGY: We retrospectively analyzed data from patients hospitalized with nonvariceal upper gastrointestinal bleeding between January 2001-December 2011. Demographic and clinical characteristics and drug costs were documented. Univariate analysis determined possible risk factors for mortality. Statistically significant variables were analyzed using a logistic regression model. Multiple linear regression analyzed factors influencing drug costs. p < 0.05 was considered statistically significant. RESULTS: The study included data from 627 patients. Risk factors associated with increased mortality were age > 60, systolic blood pressure<100 mmHg, lack of endoscopic examination, comorbidities, blood transfusion, and rebleeding. Drug costs were higher in patients with rebleeding, blood transfusion, and prolonged hospital stay. CONCLUSION: In this patient cohort, re-bleeding rate is 11.20% and mortality is 5.74%. The mortality risk in patients with comorbidities was higher than in patients without comorbidities, and was higher in patients requiring blood transfusion than in patients not requiring transfusion. Rebleeding was associ ated with mortality. Rebleeding, blood transfusion, and prolonged hospital stay were associated with increased drug costs, whereas bleeding from lesions in the esophagus and duodenum was associated with lower drug costs. PMID- 26902027 TI - Segmental Duodenectomy in Surgical Therapy of Tumor of the Third and Fourth Portions of Duodenum. AB - BACKGROUND/AIMS: To analyze our experience of segmental duodenectomy for tumors located at the third and fourth portion of the duodenum and attempt to explore the security and feasibility of this surgical procedure. METHODOLOGY: A retrospective cohort study of five patients who underwent segmental duodenectomy in our hospital, medical records were analyzed in this study. RESULTS: The initial symptoms in five patients are not specific. Five were surgically treated by segmental resection. All patients without postoperative anastomotic leakage, the gastroparesis and anastomotic stenosis each appeared in a case and all recovered after supportive care. Pathological examination showed: 3 cases of stromal tumor, 1 :ases of lymphangioma, diffuse large B-cell lymphoma. Postoperative gastrointestinal bleeding does not appear in the lymphangioma,two cases of high risk group of stromal tumor patients received targeting therapy with Imatinib Mesylate for 2 years after resection, the patient with lymphoma administer postoperative adjuvant chemotherapy. All patients are still alive and the lymphoma patient developed postoperative local recurrence after approximately six months. CONCLUSIONS: Segmental duodenectomy is a reliable and curative option for most duodenal benign tumor and stromal tumor located at the third and fourth portion. It is also applicable to some malignant tumor. PMID- 26902029 TI - Weak Points of a Stapled Side-to-Side Anastomosis. AB - BACKGROUND/AIMS: In recent years, the side-to-side intestinal anastomosis has become a widely used technique. The purpose of this study was to evaluate the difference in the burst pressures and weak points using three different kinds of suture instruments. METHODOLOGY: Fresh pig esophagus and small bowel were used for all experiments. A side-to-side anastomosis was performed using three linear staplers, and the burst pressure was measured. Stapling devices used were the GIATM60-3.8, Endo GIATM60-3.5 and 60AMT. RESULTS: In the GIATM6O-3.8 group, mean burst pressure was 34.5mmHg, with the burst point being the side of the staple line in one case, the side and the crotch simultaneously in two cases, and the crotch alone in two cases. In the GIA TM60-3.5 and 60AMT groups, mean burst pressure was 74.3 mmHg and 55.5 mmHg, and the burst point was the crotch in all cases. The difference between the instruments was significant. CONCLUSION: With two-row stapling devices, the side and the crotch of the staple line are equally weak. On the other hand, three-row staplers have not only greater burst pressures, but also the only weak point is the crotch. Thus, crotch reinforcement in side- to-side stapled anastomoses is critical regardless of the amount of rows used. PMID- 26902028 TI - Risk Classification using the Ki-67 Labeling Index for Surgically-Treated Gastric Gastrointestinal Stromal Tumors. AB - BACKGROUND/AIMS: Adjuvant treatment with imatinib mesylate (IM) improves survival of patients with a high risk of recurrence of gastrointestinal stromal tumors (GISTs). However, the optimal adjuvant treatment strategy remains unknown. Thus, this study aimed to identify patients who do not require adjuvant IM treatment using the Ki-67 labeling index (LI). METHODOLOGY: The Ki-67 LI was calculated in 59 patients with gastric GISTs. A new risk classification using the Ki-67LI and tumor size was established using cut-off values determined by receiver operating characteristic analysis. This Ki-67 classification was compared with the modified Fletcher classification (MF). RESULTS: The best cut-off values for the Ki-67LI and tumor size were 8.6% and 80 mm, respectively. According to the MF, 42, 10, and 7 patients were categorized as low, intermediate, and high risk, respectively, while the Ki-67 classification rated 38, 17, and 4 patients as low, intermediate, and high risk, respectively. The 7 patients classified as high risk by MF were graded high risk (4 patients) and intermediate risk (3 patients) by the Ki-67 classification. Recurrence was not observed in patients classed intermediate risk by the Ki-67 classification. CONCLUSIONS: The Ki-67 classification is helpful for identifying patients for whom adjuvant IM treatment is not necessary. PMID- 26902030 TI - Contrast-Enhanced Ultrasonography in Crohn's Disease Diagnostics. AB - The chronic nature of Crohn's disease (CD) implicates necessity of multiple control assessments throughout patient's life. It is accepted that in patients with CD requiring disease monitoring, magnetic resonance enterography (MRE) and computed tomography enterography (CTE) are--apart from endoscopy--imaging studies of first choice. In practice, diagnostic imaging of patients with CD is troublesome, since MRE is an expensive and complicated study, and CTE exposes patients to high doses of ionizing radiation. Therefore, there is a need for new, both non-invasive and effective, methods of imaging in CD. Contrast-Enhanced Ultrasonography (CEUS) is a relatively new method using gas-filled microbubbles serving as contrast agent. It allows for detailed assessment of blood perfusion within intestine wall and peri-intestinal tissues, which enables detection and monitoring of inflammation and its qualitative assessment. The purpose of this paper is to describe CEUS examination technique and its clinical applications in patients with Crohn's disease. PMID- 26902031 TI - Liver Transplantation for Non-B and Non-C Hepatocellular Carcinoma. AB - BACKGROUND/AIMS: Few studies have characterized the outcomes and clinical features of patients who undergo liver transplantation (LT) for hepatocellular carcinoma (HCC) due to non-viral causes. METHODOLOGY: We retrospectively analyzed 188 patients with HCC who underwent LT between February 1999 and October 2010. The clinicopathological factors and overall survival rates as well as recurrence rates of 17 patients with non-hepatitis B virus (HBV) and non-hepatitis C virus (HCV) infection (NBNC group) and 171 patients with HBV or HCV infection (HBV/ HCV group) were compared. RESULTS: HCC patients in the NBNC group were significantly younger at time of transplant, had higher serum des-gamma-carboxy prothrombin levels, and had larger pathological tumor size when compared with patients in the HBV/ HCV group. Overall survival rates were lower, and recurrence rates were higher in the NBNC group than in the HBV/HCV group. However, both these rates were significantly improved in NBNC patients who met our expanded selection criteria when compared with those that did not meet these criteria. CONCLUSIONS: The patients with NBNC HCC had more advanced and biologically aggressive tumors with inferior outcomes when compared with those with HBV/HCV. However, use of appropriate selection criteria for LT yields improved outcomes even in this subgroup of patients. PMID- 26902032 TI - Liver Transplantation in Adults with Acute Liver Failure: A Single Center Experience over A Period of 15 Years. AB - BACKGROUND/AIMS: Liver transplantation (LT) is an effective treatment modality for acute liver failure (ALF). However, no reports have examined a large number of patients who underwent adult living donor LT (LDLT) for ALF. METHODOLOGY: Seventy-four adult patients who underwent LT including 72 LDLT in a single center over a period of 15 years were reviewed. RESULTS: Of 74 cases, there were 17 cases with acute type ALF and 57 cases with subacute type of ALF. Etiologies of hepatitis were hepatitis B virus in 31 cases, drug exposure in 11 cases, autoimmune hepatitis in two cases, and unknown in 30 cases. Patient survival was 65%, 65%, and 61% at 1, 3, and 5 years, respectively. The overall survival rates did not differ among patients divided by etiology of ALE (p = 0.693), type of ALE (p 0.745), ABD compatibility (p a, 0.912), total scores for predictive variables (p = 0.975), or graft-to-recipient weight ratio greater or less than 0.8% (p = 0.063). The most frequent cause of death within 1 month aftet LT was infection. CONCLUSION: LT produces favorable outcomes in adult patients with ALE irrespective of etiology, type of ALE, or pre-transpiant liver conditions. PMID- 26902033 TI - Outcomes and Prognostic Factors in Patients with Spontaneously Ruptured Hepatocellular Carcinoma. AB - BACKGROUND/AIMS: Spontaneous rupture is a life-threatening complication of hepatocellular carcinoma (HCC). Although hemostasis can be achieved by transarterial embolization (TAE), the prognosis remains poor. The aims of this study were to evaluate the effectiveness of emergent TAE for ruptured HCC and to clarify the prognostic factors. METHODOLOGY: Thirty-six patients with spontaneously ruptured HCC were retrospectively analyzed. Prognostic factors of short-term (57 days) and long-term (>7 days) survival after HCC rupture were investigated by univariate and multivariate analyses. RESULTS: Emergent TAE was performed in 22 patients and conservative treatment was applied in 14. The hemostasis rate of TAE was 86.4%, and median survival time in patients with TAE was significantly longer than that in patients with conservative treatment (142 days vs. 5 days, p = 0.0006). In multivariate analysis, high serum creatinine (p = 0.036) was a significant independent predictor of poor 7-day survival, and low serum albumin (p = 0.050) and absence of emergent TAE (p = 0.061) tended to be associated with poor 7-day survival. HCC treatment within the past 12 months (p = 0.048) and, high serum total bilirubin (p = 0.016) were predictors of poor long term survival. Conclusions: We identified some survival predictors after HCC rupture. Emergent TAE appears to be effective for improving short-term oroLnosis after HCC ruoture. PMID- 26902034 TI - Interleukin 28B Polymorphism Predicts Treatment Outcome Among Egyptian Patients Infected With HCV Genotype 4. AB - BACKGROUND/AIMS: Egypt has the highest prevalence of HCV worldwide (15%) with a high morbidity and mortality from chronic liver disease, cirrhosis, and hepatocellular carcinoma. The Aim of this study was to investigate the associations between IL-28B single nucleotide polymorphisms (SNP rs12979860) and treatment outcome among Egyptian patients infected with HCV genotype 4. METHODOLOGY: HCV patients were genotyped as CC, CT, or TT at the polymorphic site, rs12979860 in unrelated case control of Egyptian population with HCV. RESULTS: By using univariate regression analysis, the minor allele of IL28B (p < 0.0001), high serum level of HCV-RNA (p = 0.035), and advanced fibrosis (p = 0.02) were associated with (NRs) (Odds ratio, 3.75 with 95% confidence nterval (2.308-6.1067). While, in multivariate logistic regression analysis, rs12979860 CC genotype was the strongest predictive of SVR (OR = 20.83, 95% CI = 11.63- 37.04, p < 0.0001). CONCLUSION: The IL28B rs12979860 SNP is the strongest predictor of an SVR among Egyptian patients infected with HCV-4. PMID- 26902035 TI - Oxidized Regenerated Cellulose Reduces the Amount of Fluid Drainage after Liver Resection: A Randomized Prospective Clinical Trial. AB - BACKGROUND/AIMS: Oxidized regenerated cellulose (ORC) has been registered as adjuncts to stimulate hemostasis in liver surgery. However, most previous studies were primarily designed to study the intra-operative hemostatic efficacy, and the effect on prophylactic application was never studied as a primary endpoint. This randomized prospective clinical trial was undertaken to evaluate whether ORC is safe and effective when used as a prophylactic agent covering the raw cut surface during the hepatectomy to reduce the volume and duration of drainage. METHODOLOGY: Between June 2011 and August 2012, a total of 40 patients undergoing major hepatectomy were randomly assigned to ORC or control groups (20 in each group). Patient characteristics, resection-related factors, debit of drainage and postoperative complications were compared between the two groups. RESULTS: The two groups were comparable in terms of demographics, indications for surgery, extent of hepatectomy, and intraoperative blood loss. The amount of drainage after operation was significantly less in the ORC group compared with the control group (406.9 +/- 308.1 vs. 627.0 +/- 301.6 ml, P = 0.028). CONCLUSIONS: Application of ORC covering the raw cut surface during the hepatectomy can significantly decrease the amount of drainage. PMID- 26902036 TI - Survival after Liver Transplant: Influence of Progression of Disease and of Restoration of the "Milan" Criteria in Patients with Hepato-cellular Carcinoma undergoing Down-staging Procedures. AB - BACKGROUND/AIMS: Selection of patients with hepa- to-cellular carcinoma for liver transplantation is gen- erally performed according to the so-called Milan cri- teria. The aim of this study was to learn whether, after down-staging loco regional therapies, patients origi- nally non-fulfilling the MC (Milan-OUT) meet these criteria (Milan-IN). METHODOLOGY: Between January 2000 and December 2008, 172 patients with HCC re- ceived LT at our Department. Of these, 142 were sub- jected to DS before LT. RESULTS: Of the 142 patients who received DS, 115 (81%) were Milan-IN and 27 (19%) were Milan-OUT at the time of their enrollment in the waiting list for LT. After a median follow-up of 50 months, overall 1-, 3-, and 5 year survival and dis- ease recurrence-free survival were not significantly different. CONCLUSIONS: Patients with Milan-OUT HCC can be successfully subjected to LT when they fulfill the MC after being subjected to DS. Imaging progres- sion while on the waiting list is a strong predictor of high rates of HCC recurrence even in patients meet- ing the MC. Lack of imaging progression seems to be a strong predictor of positive LT outcome and should be added to the eligibility criteria for the assessment of LT candidates with HCC. PMID- 26902037 TI - Primary and Metastatic Liver Malignancy: Utility Low and High B Value (1600-2000) in 3 Tesla MRI. AB - BACKGROUND/AIMS: To determine the utility of the quantitative apparent diffusion coefficient (ADC) values at various b values, in the differentiation of malignant hepatic masses on 3.0 Tesla (T) MRI. METHODOLOGY: We evaluated 81 consecutive patients presenting with 529 malignant masses in the liver. Of those patients 27 had a primary hepatic malignancy while the other 54 patients had metastases in the liver. Quantitative ADC values of malignant hepatic masses was measured at four b values (b 400, b 800, b 1600, b 2000 mm2/s) on MR-DWI. We compared the primary and metastatic tumors within their groups and also with each other in terms of their ADC values. RESULTS: In 4 various b value measurements, the mean ADC values of the primary and metastatic hepatic masses were 1. x 10(-3), 1.06 x 10(-3), 0.87 x 10(-3), and 0.736 x 10(-3)mm2/ seconds, 1.30 x 10(-3), 1.10 x 10( 3), 0.84 x 10(-3), and 0.715 x 10(-3) mm2/seconds respectively. There was no significant difference between mean ADC values of HCCs and metastases at b 400, 800, 1600 and 2000 gradients (P > 0.05). CONCLUSIONS: The ADC values obtained at intermediate (400, 800) and high (b 1600, 2000) diffusion gradients are not helpful in differentiation between HCCs and liver metastases. PMID- 26902038 TI - C-Reactive Protein as a Prognostic Marker in Patients with Hepatocellular Carcinoma. AB - C-reactive protein (CRP) is an acute phase reactant synthesized by hepatocytes that is regulated by pro-inflammatory cytokines, particulary interleukin-6 (IL 6). Over the last decade, CRP has been reported to be associated with a poor prognosis in patients with various types of cancer. Although the mechanisms by which the systemic inflammatory response reflected by an elevated serum CRP level influences survival in patients with cancer have not been fully elucidated, several possibilities involving the activation of IL-6, thereby elevating the CRP level, in cancer patients have been proposed. With regard to hepatocellular carcinoma (HCC), since Hashimoto et al. first demonstrated that the preoperative serum CRP level is an independent and significant factor predictive of a poor prognosis in patients undergoing surgical resection, several investigators have identified an elevated serum CRP level to be an indicator of poor outcomes in HCC patients undergoing transplantation, transarterial chemoembolization, radiofrequency ablation, percutaneous ethanol injection and best supportive care. Recently, the CRP level has been reported to be clinically applicable as a marker of treatment outcomes in HCC patients. However, large-scale, prospective validation studies are needed to confirm these results. PMID- 26902039 TI - Multidisciplinary Approach in Hepatocellular Carcinoma in a Level II Hospital: The First Decade of Hospital Universitario Fundacion Alcorcon. AB - BACKGROUND/AIMS: Mean survival in hepatocellular carcinoma remains low. Many efforts have been done during the last years through screening, diagnosis and treatment to improve the results. The aim of this work is to present the experience of our hospital multidisciplinary group during the first decade of this century. METHODOLOGY: The patients with hepatocellullar carcinoma presented at the multidisciplinary meeting from 1999 to 2009 were prospectively studied. According to the tumor and functional status they were treated through the current available guidelines by transplant, partial hepatectomy, local/regional procedures, systemic or symptomatic treatment. RESULTS: One hundred and forty two patients were studied. Median tumor size was 3 cm. A single tumor was diagnosed in 64.8% of the patients. Eighteen patients had liver resection (6 transplantation and 12 with partial resection), 53 tumors were not treated due to advanced stage or liver dysfunction, and in the remaining patients radiofrequency, ethanol or embolization treatments were used, single or combined. CONCLUSIONS: a multidisciplinary approach of hepatocellular carcinoma in a second level hospital with trained professionals permits a diagnosis in early tumoral and functional stages in the majority of patients, and a variety of possible treatments with adequate survival outcomes. PMID- 26902040 TI - Use of 18F-FDG PET Scan and Ultrasound-guided Biopsy in the Diagnosis of Hepatic Carcinomas. AB - BACKGROUND/AIMS: PET is a highly specific tool in liver cancer diagnosis. However, in small hepatic lesions, typical imaging characteristics are lacking. The aim of this study was to investigate the accuracy of PET-CT and ultrasound guided biopsy for diagnosis of liver carcinomas. METHODOLOGY: Clinical data of 58 patients who were diagnosed and treated in our hospital from January 2008 to December 2012 were retrospectively reviewed. Before surgery, patients received PET-CT assessment, ultrasound examination, and ultrasound-guided biopsy of liver tissues. Forty three patients with cancer underwent partial hepatectomy. Clinical data were collected from hospital records and follow-up questionnaires. RESULTS: Postoperative histology revealed hepatocellular carcinoma in 26 patients (46.4%), liver metastases in 12 patients (21.4%). Only 4 patients (7.1%) had cholangiocarcinoma. The sensitivity of PET-CT, ultrasound, and ultrasound-guided biopsy for diagnosis of hepatocellular carcinoma (HCC) was 92.9%, 95.5%, and 100%, respectively. The surgery-related complication rate was 3.6%. Prognosis was good, with 1- and 3-year survival rates of 83.4% and 67.9%, respectively. CONCLUSIONS: PET-CT is highly specific for diagnosis of hepatic cancer, which is consistent with the diagnosis of ultrasound-guided biopsy and postoperative histological assessments. Combination use of PET-CT, ultrasound assessment and ultrasound-guided biopsy will provide the most accurate diagnosis of liver cancer. PMID- 26902041 TI - Head-To-Head Comparison of Two Years Efficacy of Entecavir and Tenofovir in Patients with Treatment-Naive Chronic Hepatitis B--The Real Life Data. AB - BACKGROUND/AIMS: Entecavir and tenofovir are generally accepted as first-line therapeutic options in chronic hepatitis B. Both of them are potent and have high genetic barrier to viral resistance. Aim of this study was to compare the two year efficacy of entecavir and tenofovir in treatment-naive chronic hepatitis B patients. METHODOLOGY: Study was comprised 164 patients with treatment naive chronic hepatitis or compensated liver cirrhosis. At least twenty four mouths of entecavir or tenofovir were given to all patients. RESULTS: Mean ALT levels, ALT normalization rates, mean HBV DNA levels, HBV DNA negativity rates and HBeAg negativity rates were not different in entecavir and tenofovir groups throughout the study. Mean serum creatinine levels were also similar between groups. CONCLUSIONS: Two-years of antiviral treatment of treatment-naive patients with chronic hepatitis B or cirrhosis with entecavir or tenofovir were equally effective. PMID- 26902042 TI - Portal Vein Embolization Followed by Liver Resection versus Liver Resection Alone: a Comparison of Liver Regeneration Dynamics. AB - BACKGROUND/AIMS: Portal vein embolization (PVE) is an accepted procedure, which, by redirecting portal vein flow toward specific hepatic segments, is able to pre operatively increase the volume of the future liver remnant (FLR). The consequent reduction of liver dysfunction risk enables to extend the number of pa tients eligible for major hepatic resection. This study aims at comparing liver regeneration dynamics and long-term volumetric recovery after major hepatic re section preceded by PVE versus major hepatic resec tion not preceded by PVE. METHODOLOGY: Data from 24 consecutive patients who underwent PVE prior to major hepatic resection were collected and compared to 24 consecutive patients who underwent major hepatic resection, but on whom PVE was not performed. RESULTS: A significant growth of the FLR was observed after PVE. The liver remnant underwent a further regeneration burst after resection, with long-term volumetric recovery rates around 85% of the estimated total liver volume, similar to those observed for the control group and to those previously documented in the relevant literature. CONCLUSION: PVE gives a first impulse to liver regeneration before liver resection without compromising further regeneration after resection, resulting in long-term volumetric recovery rates similar to those known for regeneration after liver resection without prior PVE. PMID- 26902043 TI - Effect of Acute Normovolemic Hemodilution Combined with Controlled Low Central Venous Pressure on Blood Coagulation Function and Blood Loss in Patients Undergoing Resection of Liver Cancer Operation. AB - BACKGROUND/AIMS: This paper aims to investigate the effect of acute normovolemic hemodilution (ANH) used with controlled low central venous pressure (LCVP) technology on perioperative bleeding and coagulation in hepatocellular carcinoma operation patients. METHODOLOGY: A total of 60 cases undergoing hepatic resection operation were randomly divided into the control group, LCVP group (Group II), and ANH + LCVP group (Group III). The changes of hemodynamic indexes at different time points in each group were observed and recorded, along with the volume of allogenous blood transfusion and the number of patients undergoing allogenous blood transfusion. RESULTS: Compared with Group I (control), there was evident reduction of the bleeding volume, allogenic blood transfusion volume, and number of patients undergoing allogenic blood transfusion in Groups II and III. CONCLUSION: The application of ANH combined with LCVP in hepatic resection can evidently reduce intraoperative hemorrhages and homologous blood transfusions; moreover, it has no significant adverse effect on the coagulation function. PMID- 26902044 TI - Study on the Function of Tumor Necrosis Factor alpha Before and After Mutation in Hepatitis B. AB - BACKGROUND/AIMS: To explore the cause of functional changes of TNF-alpha in removing hepatitis B virus (HBV) through the structural changes of each site in TNF-alpha before and after mutation. METHODOLOGY: Three typical mutant sites (TNF alpha-308G/A, 857C/T and 863C/A of TNF-alpha) were chosen and methods like ab initio modeling was adopted for 3D modeling of TNF-alpha before and after mutation. The structural changes were also analyzed. Then structural changes and functional changes were brought together for comparison to infer the root cause of the changes. RESULTS: Mutation of TNF-alpha-308G/A led to the production of multiple helical structures and that of 863C/A caused the production of one helical structure in its adjacent region. Mutation of 857C/T, however, did not cause the change in the basic structure of TNF-alpha. CONCLUSIONS: The helical structure of TNF-alpha may have a positive effect on the removal of hepatitis B virus. PMID- 26902045 TI - Meta-Analysis of Doxorubicin-Eluting Beads via Transcatheter Arterial Chemoembolization in the Treatment of Unresectable Hepatocellular Carcinoma. AB - BACKGROUND/AIMS: To evaluate the efficacy and safety of doxorubicin-eluting beads combined with transcatheter arterial chemoembolization (DEB-TACE) compared with conventional TACE (cTACE). METHODOLOGY: PubMed, EMBASE, MEDLINE and Cochrane Controlled Trials Register were searched for articles published to identify randomized controlled trials evaluating efficacy and side effects between DEB TACE and cTACE. The RR (relative risk) with a 95% confidence interval (CI) was calculated by the Revman 5.0 software. RESULTS: Totally 4 studies, including 527 patients, compared the efficacy and safety of DEB-TACE with cTACE. The DEB-TACE achieved fewer side effects in alopecia (p = 0.0002, RR = 0.05, 95% CI: 0.01 0.24) and myelosuppression (p = 0.009, RR = 0.32, 95% CI: 0.14-0.75). Meanwhile, there was no significant difference in efficacy evaluation including complete response (p = 0.16, RR = 1.36, 95% CI: 0.89-2.08), partial response (p = 0.48, RR = 1.14, 95% CI: 0.80-1.62), stable disease (p = 0.73, RR = 0.93,95% CI: 0.60 1.40), progressive disease (p 0.19, RR = 0.80, 95% CI: 0.56-1.12), objective response (p = 0.26, RR 0.91, 95% CI: 0.48-1.72) and disease control (p = 0.05, RR = 1.18, 95% CI: 1.00-1.39). CONCLUSIONS: DEB-TACE shows similar therapeutic efficacy to cTACE method and fewer adverse events. PMID- 26902046 TI - Effect of Mast Cell Chymase on Activation, Proliferation and Transdifferentiation of Hepatic Stellate Cells. AB - BACKGROUND/AIMS: This work aims to observe the effects of mast cell (MC) chymase on activation, proliferation and transdifferentiation of hepatic stellate cells (HSCs) and to discuss the role of chymase in development of liver fibrosis. METHODOLOGY: Rat HSCs were isolated by in situ perfusion using collagenase IV and proteinase E and density gradient centrifugation (Percoll method), followed by culture. After intervention by chymase with series of concentration (1, 10 and 100 ng/mL), MTT assay was performed to determine HSC proliferation. Expressions of alpha-SMA and TGF-beta1 protein in HSCs were determined by Western blotting method, and TGF-beta1 and Col-I mRNA expression were determined using semi quantitive RT-PCR method. RESULTS: MC Chymase could significantly promote the proliferation of HSCs (P < 0.05), with chymase concentration dependence from 1 ng/mL to 100 ng/mL. The OD value of HSCs in 100 ng/ml chymase group was 1.45 times to control group. Compared with control group, expressions of alpha-SMA and TGF-beta1 protein and expressions of TGF-beta1 and Col-I mRNA in chymase groups were significantly increased, respectively (P < 0.05), with chymase concentration dependence. CONCLUSIONS: MC chymase can promote the activation, proliferation and transdifferentiation of HSCs, and plays an important role in occurrence and development of liver fibrosis. PMID- 26902047 TI - The Charlson Comorbidity Index is an Independent Prognostic Factor for Treatment Naive Hepatocellular Carcinoma Patients with Extrahepatic Metastases. AB - BACKGROUND/AIMS: This study aimed to investigate the association between comorbidity, anti-cancer treatment, and overall survival in patients with hepatocellular carcinoma (HCC) with extrahepatic metastases. METHODOLOGY: We retrospectively analyzed data from 57 patients diagnosed as having treatment naive stage IV HCC with extrahepatic metastases between 2007 and 2010. Comorbidity was assessed using two scoring systems, the Charlson comorbidity index (CCI) and the Kaplan-Feinstein index. Associations between comorbidity, demographic variables, treatment modality, and overall survival were analyzed. RESULTS: Univariate analysis showed that a CCI of >= 2 (P = 0.017), an Okuda score of II/III (P = 0.026), and the use of anti-cancer therapy (P = 0.039) was associated with overall survival. Fewer patients with a CCI of >= 2 received treatment (P < 0.001), and anti-cancer treatment of any modality did not show a survival benefit in these patients (P = 0.174). The multivariate analysis showed that a CCI of >= 2 was the only independent prognostic factor for overall survival (P = 0.043). CONCLUSIONS: The pre-treatment comorbidity status played an important role in overall survival because of its association with the administration of anti-cancer therapy. Therefore, comprehensive evaluation of comorbidities before treatment is recommended for HCC patients with extrahepatic metastases. PMID- 26902048 TI - Hydrodynamics Analysis and CFD Simulation of Portal Venous System by TIPS and LS. AB - In cirrhotic patients, portal hypertension is often associated with a hyperdynamic changes. Transjugular Intrahepatic Portosystemic Shunt (TIPS) and Laparoscopic splenectomy are both treatments for liver cirrhosis due to portal hypertension. While, the two different interventions have different effects on hemodynamics after operation and the possibilities of triggering PVT are different. How hemodynamics of portal vein system evolving with two different operations remain unknown. Based on ultrasound and established numerical methods, CFD technique is applied to analyze hemodynamic changes after TIPS and Laparoscopic splenectomy. In this paper, we applied two 3-D flow models to the hemodynamic analysis for two patients who received a TIPS and a laparoscopic splenectomy, both therapies for treating portal hypertension induced diseases. The current computer simulations give a quantitative analysis of the interplay between hemodynamics and TIPS or splenectomy. In conclusion, the presented computational model can be used for the theoretical analysis of TIPS and laparoscopic splenectomy, clinical decisions could be made based on the simulation results with personal properly treatment. PMID- 26902049 TI - Which Factors are Predictive for Mortality among Hospitalized Patients with Cirrhosis? AB - BACKGROUND/AIMS: Cirrhotic patients admitted to the hospital have a high mortality rate. The aim of this study was to evaluate predictors of mortality in patients hospitalized for specific complications of cirrhosis. METHODOLOGY: All patients admitted to the gastroenterology service with cirrhosis during a 2-year period were retrospectively identified. We compared the clinical characteristics of patients who died and those who survived. Multivariable analysis was performed to determine predictors of mortality. RESULTS: A total of 84 patients were included in the study. In hospital mortality rate was 35%. Hepatorenal syndrome development (41% vs 4%, p < 0.001), MELD score (17 vs 12, p = 0.003), Child Pugh score (11 vs 8, p < 0.001), serum creatinine (p < 0.001) and serum potassium values (p = 0.01) were significantly higher in patients who died. Stepwise logistic regression analysis revealed that the best model in prediction of death included serum potassium levels (OR = 2.182; 95% Cl: 1.189-4.006; p < 0.001) and Child Pugh score (OR = 2.140; 95% CI: 1.507-3,038; p = 0.012). CONCLUSIONS: The mortality of cirrhotic patients admitted to hospital is significantly high. Prevention of acute kidney injury will be an appropriate approach for improving the survival in hospitalized patients with cirrhosis. PMID- 26902050 TI - A Novel Approach for Endoscopic Papillary Balloon Dilation with the Guidewire Left in the Pancreatic Duct to Ensure Pancreatic Stenting. AB - BACKGROUND/AIMS: Endoscopic papillary balloon dilation (EPBD) was reported to be superior for preserving the function of the sphincter of Oddi and to cause fewer late complications than endoscopic sphincterotomy. If the early complication of post-EPBD pancreatitis can be prevented, EPBD might be useful as long-term outcomes. This study assessed the feasibility of a novel EPBD for the purpose of reliable post-EPBD pancreatic stenting. METHODOLOGY: Among 1814 ER-CPs, in 17 patients undergoing biliary cannulation with pancreatic duct guidewire placement method, we performed EPBD with the guidewire left in the pancreatic duct by the two-devices-in-one-channel method. This approach employed in order to ensure pancreatic stenting. RESULTS: Procedures were successfully performed without the guidewire displacement, and pancreatic stents were easily placed in all patients. Post-EPBD pancreatitis occurred in only 1 patient (5.9%), and the severity was mild. Asymptomatic hyperamylasemia occurred in 3 patients (17.6%). There were no other early complications. The mean serum amylase levels (mean +/- SD) before, 1 day, and 2 days after procedure were 81.4 +/- 61.9, 301.2 +/- 273.0, and 220.0 +/ 177.6 IU/L. CONCLUSIONS: EPBD with a guidewire left in the pancreatic duct is useful method allowing reliable pancreatic stenting and may contribute to the prevention of pancreatitis. PMID- 26902051 TI - A Phase I Study of S-1 and Gemcitabine with Concurrent Radiotherapy in Patients with Non-Metastatic Advanced Pancreatic Cancer. AB - BACKGROUND/AIMS: To determine the recommended dose (RD) for full-dose S-1 and low dose gemcitabine combined with radiotherapy in patients with non-metastatic advanced pancreatic cancer. METHODOLOGY: Adult patients with non-metastatic advanced pancreatic cancer (Union for International Cancer Control T stage 3 or 4) were eligible. The weekly intravenous gemcitabine (level 0-1: 200 mg/ml,level 2: 300 mg/m on Days 1, 8, 15, 22, 29, 36) dose was escalated starting from level 1 in a 3+3 design along with full dose twice-daily oral S-1 (level 0: 60 mg/m2/day, level 1-2: 80 mg/ml/day), and was administered on the same days as radiotherapy (1.8 Gy x 28 days). RESULTS: Eight patients were included in this study. A dose-limiting toxicity (DLT) (grade 4 neutropenia) was observed in one of the first three patients in level 1, and three additional patients received the level 1 dose without any severe adverse events. DLTs (grade 3/4 neutropenia) were then observed in the first two patients given level 2 dose. Therefore, level 1 was designated as the RD. Common grade 3/4 toxicities included neutropenia (62.5%), anorexia (37.5%), and pneumonitis (12.5%). CONCLUSIONS: The combination of S-1 and gemcitabine with concurrent radiotherapy is a feasible regimen at the level 1 dose. PMID- 26902052 TI - A Novel "Artery First" Approach Allowing Safe Resection in Laparoscopic Pancreaticoduodenectomy: The Uncinate Process First Approach. AB - BACKGROUND/AIMS: Laparoscopic pancreaticoduodenectomy (LPD) is still a challenging operation, particularly because the dissection around the superior mesenteric artery (SMA) and bleeding control are difficult. Although it has been reported that early ligation of the origin of the inferior pancreaticoduodenal artery (IPDA) reduces blood loss, it is difficult to laparoscopically expose the origin of the IPDA. We sought to develop a novel approach to simplify the dissection of the IPDA and reduce bleeding. METHODOLOGY: The uncinate process was exposed at the left posterior side of the SMA, and the branches of the IPDA were divided at positions where they enter and exit the uncinate process before isolating the pancreatic head from the right aspect of the SMA. Ten patients were operated using this new approach, and the results were retrospectively compared to those of 22 patients treated with conventional LPD. RESULTS: The operation times did not differ significantly between the two groups. However, the intraoperative blood loss was significantly lower in the "uncinate process first" group than in the conventional LPD group. (162.7 ml vs. 463.8 ml, respectively; P = 0.023). CONCLUSIONS: The new approach facilitates the initial dissection of the IPDA at the right side of the SMA, reducing intraopera- tive blood loss. PMID- 26902053 TI - Palliative Surgery for Gastric Cancer with Gastric Outlet Obstruction or Anemia due to Tumor Bleeding. AB - BACKGROUND/AIMS: The aim of this study was to evaluate the surgical outcomes after palliative surgery for patients with incurable gastric cancer. METHODOLOGY: This retrospective study included 45 patients with gastric outlet obstruction (GOO) who needed parental nutrition and 33 patients with anemia due to tumor bleeding who required blood transfusions. We compared the surgical outcomes of palliative gastrectomy (PG) and bypass surgery (BS) in each group. RESULTS: In the GOO patients, the clinical success rate, as indicated by a resumption of an oral diet, was similar in the PG and BS groups. The time to treatment failure, when the GOO patients again required parental nutrition, was also similar between the two groups. In the anemia patients, the clinical success rate of the PG group was higher than that of BS group, and the post-operative performance status (PS) of the PG group was also better than that of the BS group, although the pre operative PS were similar in both groups. CONCLUSIONS: PG for the GOO patients gave little advantage compared to BS, and was associated with a longer operation, higher blood loss and more frequent complications. PG may be recommended for patients with GOO when they simultaneously have anemia due to tumor bleeding. PMID- 26902054 TI - [History of Knowledge Perspectives on the Military: An Introduction]. PMID- 26902055 TI - [Medecine, Law, and Knowledge Production about the "Civilized" War in the Long 19th Century]. AB - The aim to 'civilize' warfare accompanied Medicine and International Law ever since the mid-19th century. However, the entanglement of Medicine and Law, crucial for such an endeavour, has not been taken into consideration so far; likewise, the huge importance of medical knowledge for the perception of wars and their ramifications did not garner much attention in historical research. Hence, by focusing on the 'long' 19th century, this paper shows, firstly, that the production of surgical knowledge during warfare aimed at measuring the effects of combat on human bodies in order to develop prognostic medical knowledge for future wars, as well as maintaining the combat strength of soldiers. Moreover, this knowledge production during warfare strived for the enhancement of medical competence in the diagnosis and treatment of wounds in general. Secondly, I show that this medical knowledge was not only relevant for warfare, but also crucial for the design of International Law: it served to nourish the debates among the so called 'civilized' nations about legitimate and illegitimate weaponry and warfare. PMID- 26902056 TI - [Military Knowledge: War Sciences and Army Libraries in France in the 19th Century (c. 1800-c. 1900)]. AB - This article analyses the development of military knowledge in France in the 19th century, both in terms of production of knowledge (especially through the Depot de la Guerre) and of transmission through a network of army libraries. The strategic dimension of this form of knowledge required a direct intervention of the state, to control or restrict the publication of sensitive data. State intervention was also necessary to coordinate and generate a unified, applied military knowledge using data submitted by members of different army branches, or by civilians. The work of military librarians and bibliologists was all the more difficult because of the very wide range of sciences which could be used by the army. Growing state intervention and public funding were thus essential for the production and transmission of military knowledge. PMID- 26902057 TI - [From the Local to the Global: French Military Surgeons, Algeria, and "Tropical Pathologies" (1830-1880)]. AB - Up to the 1860s, understanding of the disease consists first of a reflection on the ground and the situation of people on this place. This includes the writing of medical topographies and the development of a new science: medical geography. How could extra-European territories contribute to this knowledge and how this knowledge about tropics and their pathologies could contribute to the formation of an epidemiological reflection at a global level? This contribution tries to suggest the role of military doctors in this process, the importance of Algeria in this intellectual training and, finally, how this work on the "hot" countries contributed to the structuring of a professional identity. PMID- 26902058 TI - [From Geomorphological Research in the Canton of Aargau to European Military Pathologies. Entangling Anthropological Discourses of Crisis through the Army, 1860-1900]. AB - Military statistics and medical research were closely related over the 19th century. The army not only made use of these new forms of knowledge, but also provided an important institutional setting through the military medicine, which was of crucial importance to medical research in the 19th century. Besides that, Swiss military also played a crucial role in new geographical and geological research, resulting in a series of new mapping projects. This article looks on the ways, in which military context gained influence on scientific research practices in the second half of the 19th century, by analyzing the case of Heinrich Bircher's work on military recruiting statistics and the endemic goiter. New mapping projects and statistical practices were linked, transforming big parts of the country into pathological spaces. Coming from this point, the article discusses in how far the military context lead to politicizing medical discourses and, furthermore, linked them to discourses of an anthropological crisis, common in many European countries. PMID- 26902059 TI - [Mobilization of Blood: Blood Transfusion Service, Blood Group Research, and Total Defence in Switzerland, 1940-1960]. AB - During World War II and the early Cold War period, a rapid development of the blood transfusion service and a boom in blood group research occurred in Switzerland. Unprecedented volumes of blood were stored and enormous quantities of blood group data were recorded. In the following paper I will argue that this mobilization of blood was strongly shaped by military institutions and aims. The military worked closely with the Red Cross in order to build a blood transfusion service that was supposed to guarantee a permanent readiness for war and help prepare the nation for an imagined nuclear conflict. Concurrently, geneticists, anthropologists, and physicians obtained new opportunities for scientific research in collaboration with the military and the Red Cross enabling them access to comprehensive military data and modern serological laboratories. The paper points out how this cooperation between the military and the sciences influenced and transformed the cultural meanings, the medical uses of as well as the knowledge about human blood. PMID- 26902060 TI - Analysis of the Prevalence and Situation of Myopia in Adolescents from South China. AB - PURPOSE: To conduct dynamic detection of refraction changes in adolescents with myopia and analyze the correlation between different reexamination times and factors that included age of onset, initial refractive power, and rate of myopia progression. METHODS: A total of 900 adolescents (aged 6-15 years) with myopia admitted to Zhongshan Ophthalmic Center between 2009 and 2013 were randomly selected in this investigation. All participants underwent objective refraction measurement with an autorefractometer (Topcon 8900) or streak retinoscopy and subjective refraction detection with an autorefractor (Nidek) or minus-lens procedures at different time intervals (6 months, 1, and 2 years). Accurate refractive power was obtained. All data were analyzed with SPSS 18.0 statistical software. RESULTS: The mean refractive power was increased by 0.56 +/- 0.37 diopters(D) after 6 months, by 0.83 +/- 0.45 D after 1 year, and by 1.50 +/- 0.70 D after 2 years. Among the 900 adolescents, the most rapid increase in refractive power was observed at the age of 8 years at the 6-month reexamination, at the age of 8 and 9 years at the 1-year reexamination, and at the age of 7-9 years at the 2-year reexamination. The increase in index of refraction tended to diminish with aging. The different cycles of reexamination revealed a slowing of the rate of myopia progression along with the increase in the initial index of refraction. The highest rate of myopia progression was noted in low-myopic adolescents with initial refractive power ranging from -0.25 to 2.75 D. CONCLUSION: No positive correlation was documented between different cycles of reexamination and the refractive power. The increase in refractive power was associated with factors that included the reexamination cycle, age of onset, and initial refractive power. PMID- 26902061 TI - Application of Preoperative Visits during the Perioperative Period of Ophthalmic Surgery. AB - PURPOSE: To evaluate the effect of preoperative visits on patients' psychology, physiology, and behavior during the perioperative period of eye surgery under local anesthesia, with the aim of enhancing patients' cooperation with the surgery and improving their degree of satisfaction. METHODS: A total of 240 patients scheduled to undergo eye surgery between August and October 2013 were randomly divided into an observation (n = 120) and a control (n = 120) group. Patients in the observation group attended preoperative visits with nurses and received conventional nursing care. The control group received only conventional nursing. RESULTS: The Zung self-rating anxiety scale (SAS) scores were significantly lower in patients from the observation group than in the control group (P<0.05). Surgeons operating on the observation group were more satisfied with their patients' cooperation with the surgery than were surgeons operating on the controls (P < 0.01). Patients in the observation group had a significantly higher degree of satisfaction in terms of work efficiency in the operating room (P < 0.01). CONCLUSION: Preoperative visits by patients scheduled to undergo eye surgery can effectively mitigate preoperative anxiety in those patients, build up a positive attitude toward the upcoming surgery, instruct the patients to coordinate with the surgery, enhance surgical safety, and improve the patients' degree of satisfaction regarding the nursing care in the operating room. PMID- 26902062 TI - Application of a Quality Control Circle to Reduce the Wait Times between Continuous Surgeries. AB - PURPOSE: To investigate how to shorten patient wait times between continuous ocular operations and to evaluate the influence of a quality control circle (QCC) on operating room management. METHODS: QCC management was established to conduct activities. Clinical data were collected to analyze the causes of long wait times between continuous surgeries. Effective measures were undertaken correspondingly. RESULTS: The staff from QCC actively undertook measures that would significantly shorten patient wait times between continuous ocular surgeries (P < 0.05). CONCLUSION: Multiple measures, such as setting up a QCC, enhancing the arrangement of surgical procedures, establishing effective communication channels, optimizing human resources, and integrating the use of instruments, can effectively shorten patient wait times between continuous vitreous or retinal surgeries. PMID- 26902063 TI - Intravitreal Aflibercept for Macular Edema Secondary to Branch Retinal Vein Occlusion in Chinese Patients. AB - PURPOSE: To investigate the short-term efficacy and safety of intravitreal aflibercept in a case series of patients from Taiwan, China, with macular edema secondary to branch retinal vein occlusion (BRVO). METHODS: A total of 32 patients with macular edema associated with BRVO, without prior macular laser or other intervention, were enrolled consecutively from September 2013 to February 2015. The cases received single 2 mg injections of intravitreal aflibercept. Primary outcome measures included changes in central foveal thickness (CFT; 1 mm increments by spectral-domain optic coherence tomography) and best corrected visual acuity (BCVA), determined at 1, 2, and 3 months after the injection. Complications after injections were recorded. The changes in CFT and BCVA were compared with Wilcoxon sign-rank tests. RESULTS: The CFT was significantly reduced and the BCVA was significantly improved at 1, 2, and 3 months after injection (all P < 0.05). Tomography findings revealed no recurrence within 3 months. No systemic thromboembolic events, elevated intraocular pressure, retinal detachment, or infectious endophthalmitis occurred following injection. CONCLUSION: Single intravitreal aflibercept may be useful in treating macular edema associated with BRVO within 3 months. No adverse systemic or ocular effects were found in this case series. PMID- 26902064 TI - Comparison of the Educational Effect upon Myopia Prevention and Treatment between Video Demonstration and Traditional Teaching. AB - PURPOSE: To compare the education effect of video demonstrations and conventional teaching on the prevention and control of myopia. METHODS: Eighty students were randomly divided into an experimental (n = 40) and a control (n = 40) group, and each group was split into two classes of 40 students. The students in the experimental group attended classes mainly based on video demonstration and those in the control group received conventional teaching. All students then undertook a test and the examination scores were statistically compared between the two groups. RESULTS: The educational background, age, and gender did not differ between the two groups (all P > 0.05). The experimental group had a mean test score of 8.25 +/- 1.45, which was slightly lower than the mean of 8.58 +/- 1.11 in the control group, but the difference was not statistically significant (t = 1.589, P = 0.114). CONCLUSION: The educational effect of video demonstrations was almost identical to that of traditional teaching. In addition, video classes reduced the training time and financial costs, indicating that they deserve widespread application. PMID- 26902065 TI - Comparison of Dextran Perfusion and GSI-B4 Isolectin Staining in a Mouse Model of Oxygen-induced Retinopathy. AB - PURPOSE: Oxygen-induced retinopathy (OIR) is a robust and widely used animal model for the study of retinal neovascularization (NV). Dextran perfusion and Griffonia simplicifolia isolectin B4 (GSI-B4) staining are two common methods for examining the occurrence and extent of OIR. This study provides a quantitative comparison of the two for OIR detection. METHODS: At postnatal day 7 (PN7), fifteen C57BL/6J mice were exposed to a 75% hyperoxic condition for 5 days and then returned to room air conditions. At PN17, the mice received intravitreal injection of GSI-B4 Alexa Fluor 568 conjugate. After 10 hours, they were infused with FITC-dextran conjugate via the left ventricle. Retinal flat mounts were photographed by confocal microscopy. Areas with fluorescent signals and the total retinal areas were quantified by Image J software. RESULTS: Both GSI-B4 and dextran detected the peripheral neovascular area. The mean hyper fluorescence area was 0.33 +/- 0.14% of whole retinal area determined by GSI-B4 staining and 0.25 +/- 0.28% determined by dextran perfusion. The difference between the two measures was 0.08% (95% CI:-0.59%, 0.43%). The Pearson correlation coefficient between the two methods was 0.386,P =0.035. The mean coincidence rates were 14.3 +/- 13.4% and 24.9 +/- 18.5% for GSI-B4 and dextran staining, respectively. CONCLUSION: Both methods can complement each other in demonstrating and quantitatively evaluating retinal NV. A poor agreement was found between the two methods; GSI-B4 isolectin was more effective than FITC-dextran perfusion in evaluating the extent of retinal NV in a mouse model of OIR. PMID- 26902066 TI - Bilateral Frosted Branch Angiitis in a Patient with Tuberculous Meningoencephalitis. AB - PURPOSE: To present a case of frosted branch angiitis with tuberculous meningoencephalitis who was followed up for 18 months after treatment. METHODS: Case report. RESULTS: A 19-year-old female with tuberculous meningoencephalitis complained of bilateral blurred vision, and presented with frosted branch angiitis and macula edema in both eyes. Treatment with systemic glucocorticoid and standard anti-tuberculosis medicine totally resolved the retinal periphlebitis and macular edema, with vision improvement achieved at the 18-month follow-up. CONCLUSION: Frosted branch angiitis could be secondary to tuberculous meningoencephalitis. Based on standard anti-tuberculosis medicine, systemic glucocorticoid may help in the remission of frosted branch angiitis. PMID- 26902067 TI - Effect of Diplopia on Daily Life and Evaluation of Nursing Measures Following Strabismus Surgery. AB - PURPOSE: To investigate the effect of diplopia on the daily life of patients after strabismus surgery and to explore appropriate nursing care measures. METHODS: A total of 200 patients who developed postoperative diplopia underwent telephone follow-up to evaluate the influence of diplopia on their daily lives. SPSS 19.0 statistical software was utilized for data analysis. RESULTS: Postoperative diplopia affected patients' physical activity (49%), attention (39.2%), work and study (24.5%), emotions (19.5% ), and housework performance (17% ), whereas it did not influence the quality of sleep. Potential risk factors associated with diplopia, such as duration of diplopia, gender, and age, were analyzed by uni- and multivariate regression analysis. Quality of life was significantly and negatively correlated with the duration of diplopia, but not correlated with gender or age. CONCLUSION: Postoperative diplopia affects the quality of life in partial patients. The nursing staff should provide nursing care, health education, and explicit instructions to the patients after discharge. In addition, nursing care should be sustained by subsequent telephone follow-up. PMID- 26902068 TI - Study of Pigment Epithelium-derived Factor in Pathogenesis of Diabetic Retinopathy. AB - Diabetic retinopathy (DR), a major microvascular complication of diabetes, has emerged as a leading cause of visual impairment and blindness among adults worldwide. However, aside from pathological damage, the traditional laser and multi-needle operation treatments required for more advanced disease can cause further damage to the visual field and increase the operation risk. Therefore, the development of new therapeutic strategies for the prevention and treatment of DR is essential. Some emerging evidence now indicates that pigment epithelium derived factor (PEDF), a multifunctional protein, can target multiple pathways to exert neurotropic, neuropro- tective, anti-angiogenic, anti-vasopermeability, anti-inflammation, anti-thrombogenic, and anti-oxidative effects against DR. This review addresses the functions of PEDF in different pathways that could lead to potential therapeutics for the treatment of DR. PMID- 26902069 TI - Life savers, clinicians, counsellors. PMID- 26902071 TI - Irish District hosts ICD in Dublin. PMID- 26902070 TI - Dentists united on issue of child oral health. PMID- 26902072 TI - It's what you say and how you say it!. PMID- 26902073 TI - Gingival retraction. PMID- 26902074 TI - Medical emergencies in the dental surgery. Part 1: Preparation of the office and basic management. AB - STATEMENT OF THE PROBLEM: Medical emergencies can and do happen in the dental surgery. In the 20- to 30-year practice lifetime of the typical dentist, he/she will encounter between five and seven emergency situations. Being prepared in advance of the emergency increases the likelihood of a successful outcome. PURPOSE OF THE PAPER: To prepare members of the dental office staff to be able to promptly recognize and efficiently manage those medical emergency situations that can occur in the dental office environment. MATERIALS AND METHODS: Preparation of the dental office to promptly recognize and efficiently manage medical emergencies is predicated on successful implementation of the following four steps: basic life support for ALL members of the dental office staff; creation of a dental office emergency team; activation of emergency medial services (EMS) when indicated; and basic emergency drugs and equipment. The basic emergency algorithm (P->C->A->B->D) is designed for implementation in all emergency situations. RESULTS AND CONCLUSIONS: Prompt implementation of the basic emergency management protocol can significantly increase the likelihood of a successful result when medical emergencies occur in the dental office environment. PMID- 26902076 TI - Room to grow. PMID- 26902075 TI - The application of indirect composite onlays in the restoration of severely broken down posterior teeth. AB - Increasing interest has developed among dentists regarding alternatives to traditional full-coverage crowns for the restoration of extensively broken-down teeth that are both aesthetic and less destructive of remaining tooth structure. Indirectly fabricated resin composite onlays may offer a viable and cost effective treatment option in such cases. This paper describes the clinical rationale for resin-based onlays, and includes a case report illustrating the author's experience with the technique to date. PMID- 26902077 TI - Modest proposals to expand the type material for naming of prokaryotes. AB - Gene sequences are herein proposed to be suitable type material for the description of prokaryotic species. This proposal follows from the principles described in the International Code of Nomenclature of Prokaryotes. This simple change in the Code will allow for the stability of naming of Candidatus taxa, endosymbionts and uncultivated prokaryotes and will meet an important need within microbiology. In addition, modern molecular techniques allow the identification of genera even when the species remain obscure. The Code should be modified to allow gene sequences to serve as the type material for genera in the absence of described species. This simple change will unite the nomenclature of the cultured and uncultured prokaryotes into a single, robust system. PMID- 26902078 TI - Intermittent hypoxia maintains glycemia in streptozotocin-induced diabetic rats. AB - Increasing studies have shown protective effects of intermittent hypoxia on brain injury and heart ischemia. However, the effect of intermittent hypoxia on blood glucose metabolism, especially in diabetic conditions, is rarely observed. The aim of this study was to investigate whether intermittent hypoxia influences blood glucose metabolism in type 1 diabetic rats. Streptozotocin-induced diabetic adult rats and age-matched control rats were treated with intermittent hypoxia (at an altitude of 3 km, 4 h per day for 3 weeks) or normoxia as control. Fasting blood glucose, body weight, plasma fructosamine, plasma insulin, homeostasis model assessment of insulin resistance (HOMA-IR), pancreas beta-cell mass, and hepatic and soleus glycogen were measured. Compared with diabetic rats before treatment, the level of fasting blood glucose in diabetic rats after normoxic treatment was increased (19.88 +/- 5.69 mmol/L vs. 14.79 +/- 5.84 mmol/L, p < 0.05), while it was not different in diabetic rats after hypoxic treatment (13.14 +/- 5.77 mmol/L vs. 14.79 +/- 5.84 mmol/L, p > 0.05). Meanwhile, fasting blood glucose in diabetic rats after hypoxic treatment was also lower than that in diabetic rats after normoxic treatment (13.14 +/- 5.77 mmol/L vs. 19.88 +/- 5.69 mmol/L, p<0.05). Plasma fructosamine in diabetic rats receiving intermittent hypoxia was significantly lower than that in diabetic rats receiving normoxia (1.28 +/- 0.11 vs. 1.39 +/- 0.11, p < 0.05), while there were no significant changes in body weight, plasma insulin and beta-cell mass. HOMA-IR in diabetic rats after hypoxic treatment was also lower compared with diabetic rats after normoxic treatment (3.48 +/- 0.48 vs. 3.86 +/- 0.42, p < 0.05). Moreover, intermittent hypoxia showed effect on the increase of soleus glycogen but not hepatic glycogen. We conclude that intermittent hypoxia maintains glycemia in streptozotocin-induced diabetic rats and its regulation on muscular glycogenesis may play a role in the underlying mechanism. PMID- 26902079 TI - Efficiency in Drug Discovery: Liver S9 Fraction Assay As a Screen for Metabolic Stability. AB - BACKGROUND: A rapid and comprehensive metabolic stability screen at the top of a drug discovery flow chart serves as an effective gate in eliminating low value compounds. This imparts a significant level of efficiency and saves valuable resources. While microsomes are amenable to high throughput automation and are cost effective, their enzymatic make-up is limited to that which is contained in endoplasmic reticulum, thereby informing only on Phase I metabolism. Lack of Phase II metabolism data can become a potential liability later in the process, adversely affecting discovery projects' timelines and budget. Hepatocytes offer a full complement of metabolic enzymes and retain their cellular compartments, better representing liver metabolic function. However, hepatocyte screens are relatively expensive, labor intensive, and not easily automatable. Liver S9 fractions include Phase I and II metabolic enzymes, are relatively inexpensive, easy to use, and amenable to automation, making them a more appropriate screening system. We compare the data from the three systems and present the results. RESULTS: Liver S9 and hepatocyte stability assays binned into the same category 70-84% of the time. Microsome and hepatocyte data were in agreement 73-82% of the time. The true rate for stability versus plasma clearance was 45% for hepatocytes and 43% for S9. CONCLUSION: In our opinion, replacing liver microsome and hepatocyte assays with S9 assay for high throughput metabolic screening purposes provides the combined benefit of comprehensive and high quality data at a reasonable expense for drug discovery programs. PMID- 26902080 TI - Tumor-specific promoter-driven adenoviral therapy for insulinoma. AB - BACKGROUND: Insulinomas are the most common type of neuroendocrine (NE) pancreatic islet tumors. Patients with insulinomas may develop complications associated with hyperinsulinemia. To increase the treatment options for insulinoma patients, we have tested a conditionally replicating adenovirus that has been engineered in such a way that it can specifically express therapeutic genes in NE tumors. METHODS: We used a promoter-specific adenoviral vector delivery system that is regulated by an INSM1 (insulinoma-associated-1) promoter, which is silent in normal adult tissues but active in developing NE cells and tumors. Through a series of modifications, using an insulator (HS4) and neuron restrictive silencer elements (NRSEs), an oncolytic adenoviral vector was generated that retains tumor specificity and drives the expression of a mutated adenovirus E1A gene (Delta24E1A) and the herpes simplex virus thymidine kinase (HSV-tk) gene. The efficacy of this vector was tested in insulinoma-derived MIN, RIN, betaTC-1 and pancreatic (Panc-1) cells using in vitro cell survival and in vivo tumor growth assays. RESULTS: Using in vitro insulinoma-derived cell lines and an in vivo subcutaneous mouse tumor model we found that the INSM1 promoter driven viruses were able to replicate specifically in INSM1-positive cells. INSM1 specific HSV-tk expression in combination with ganciclovir treatment resulted in dose-dependent tumor cell killing, leaving INSM1-negative cells unharmed. When we combined the INSM1-promoter driven HSV-tk with Delta24E1A and INSM1p-HSV-tk (K5) viruses, we found that the co-infected insulinoma-derived cells expressed higher levels of HSV-tk and exhibited more efficient tumor suppression than cells infected with INSM1p-HSV-tk virus alone. CONCLUSIONS: INSM1 promoter-driven conditionally replicating adenoviruses may serve as a new tool for the treatment of insulinoma and may provide clinicians with additional options to combat this disease. PMID- 26902081 TI - Precision diagnosis: a view of the clinical decision support systems (CDSS) landscape through the lens of critical care. AB - Improving diagnosis and treatment depends on clinical monitoring and computing. Clinical decision support systems (CDSS) have been in existence for over 50 years. While the literature points to positive impacts on quality and patient safety, outcomes, and the avoidance of medical errors, technical and regulatory challenges continue to retard their rate of integration into clinical care processes and thus delay the refinement of diagnoses towards personalized care. We conducted a systematic review of pertinent articles in the MEDLINE, US Department of Health and Human Services, Agency for Health Research and Quality, and US Food and Drug Administration databases, using a Boolean approach to combine terms germane to the discussion (clinical decision support, tools, systems, critical care, trauma, outcome, cost savings, NSQIP, APACHE, SOFA, ICU, and diagnostics). References were selected on the basis of both temporal and thematic relevance, and subsequently aggregated around four distinct themes: the uses of CDSS in the critical and surgical care settings, clinical insertion challenges, utilization leading to cost-savings, and regulatory concerns. Precision diagnosis is the accurate and timely explanation of each patient's health problem and further requires communication of that explanation to patients and surrogate decision-makers. Both accuracy and timeliness are essential to critical care, yet computed decision support systems (CDSS) are scarce. The limitation arises from the technical complexity associated with integrating and filtering large data sets from diverse sources. Provider mistrust and resistance coupled with the absence of clear guidance from regulatory bodies further retard acceptance of CDSS. While challenges to develop and deploy CDSS are substantial, the clinical, quality, and economic impacts warrant the effort, especially in disciplines requiring complex decision-making, such as critical and surgical care. Improving diagnosis in health care requires accumulation, validation and transformation of data into actionable information. The aggregate of those processes-CDSS-is currently primitive. Despite technical and regulatory challenges, the apparent clinical and economic utilities of CDSS must lead to greater engagement. These tools play the key role in realizing the vision of a more 'personalized medicine', one characterized by individualized precision diagnosis rather than population-based risk-stratification. PMID- 26902082 TI - Quinpirole Increases Melatonin-Augmented Pentobarbital Sleep via Cortical ERK, p38 MAPK, and PKC in Mice. AB - Sleep, which is an essential part of human life, is modulated by neurotransmitter systems, including gamma-aminobutyric acid (GABA) and dopamine signaling. However, the mechanisms that initiate and maintain sleep remain obscure. In this study, we investigated the relationship between melatonin (MT) and dopamine D2 like receptor signaling in pentobarbital-induced sleep and the intracellular mechanisms of sleep maintenance in the cerebral cortex. In mice, pentobarbital induced sleep was augmented by intraperitoneal administration of 30 mg/kg MT. To investigate the relationship between MT and D2-like receptors, we administered quinpirole, a D2-like receptor agonist, to MT- and pentobarbital-treated mice. Quinpirole (1 mg/kg, i.p.) increased the duration of MT-augmented sleep in mice. In addition, locomotor activity analysis showed that neither MT nor quinpirole produced sedative effects when administered alone. In order to understand the mechanisms underlying quinpirole-augmented sleep, we measured protein levels of mitogen-activated protein kinases (MAPKs) and cortical protein kinases related to MT signaling. Treatment with quinpirole or MT activated extracellular-signal regulated kinase 1 and 2 (ERK1/2), p38 MAPK, and protein kinase C (PKC) in the cerebral cortex, while protein kinase A (PKA) activation was not altered significantl. Taken together, our results show that quinpirole increases the duration of MT-augmented sleep through ERK1/2, p38 MAPK, and PKC signaling. These findingssuggest that modulation of D2-like receptors might enhance the effect of MT on sleep. PMID- 26902083 TI - Assessment of the Cytotoxic and Apoptotic E?ects of Chaetominine in a Human Leukemia Cell Line. AB - Chaetominine is a quinazoline alkaloid originating from the endophytic fungus Aspergillus fumigatus CY018. In this study, we showed evidence that chaetominine has cytotoxic and apoptotic effects on human leukemia K562 cells and investigated the pathway involved in chaetominine-induced apoptosis in detail. Chaetominine inhibited K562 cell growth, with an IC50 value of 35 nM, but showed little inhibitory effect on the growth of human peripheral blood mononuclear cells. The high apoptosis rates, morphological apoptotic features, and DNA fragmentation caused by chaetominine indicated that the cytotoxicity was partially caused by its pro-apoptotic effect. Under chaetominine treatment, the Bax/Bcl-2 ratio was upregulated (from 0.3 to 8), which was followed by a decrease in mitochondrial membrane potential, release of cytochrome c from mitochondria into the cytosol, and stimulation of Apaf-1. Furthermore, activation of caspase-9 and caspase-3, which are the main executers of the apoptotic process, was observed. These results demonstrated that chaetominine induced cell apoptosis via the mitochondrial pathway. Chaetominine inhibited K562 cell growth and induced apoptotic cell death through the intrinsic pathway, which suggests that chaetominine might be a promising therapeutic for leukemia. PMID- 26902084 TI - Comparative Evaluation of Hepatoprotective Activities of Geniposide, Crocins and Crocetin by CCl4-Induced liver Injury in Mice. AB - Iridoid glycosides (mainly geniposide) and crocetin derivatives (crocins) are the two major active constituents in Gardenia jasminoides Ellis. In the present study, geniposide, crocins, crocin-1 and crocetin were separated from gardenia chromatographically. Then, mice were orally administrated with geniposide (400 mg/kg b.w.), crocins (400 mg/kg b.w.), crocin-1 (400 mg/kg b.w.) and crocetin (140 mg/kg b.w.) once daily for 7 days with CCl4. Hepatoprotective properties were evaluated by biochemical parameters: Administration of geniposide, crocins, crocin-1and crocetin significantlylowered serum alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) levels in CCl4 treated mice. The reduced glutathione (GSH) levels and antioxidant enzymes (SOD and CAT) activities were also increased by geniposide, crocins, crocin-1 and crocetin. Histopathological examination of livers showed that these components reduced deformability, irregular arrangement and rupture of hepatocyte in CCl4 treated mice. These biochemical results and liver histopathological assessment demonstrated that geniposide, crocetin derivatives and crocetin show comparative beneficialeffects on CCl4-induced liver damage via induction of antioxidant defense. Therefore, contents of geniposide and crocetin derivatives should be both considered for hepatoprotective efficacyof Gardenia jasminoides Ellis. PMID- 26902085 TI - Apigenin Regulates Interleukin-1beta-Induced Production of Matrix Metalloproteinase Both in the Knee Joint of Rat and in Primary Cultured Articular Chondrocytes. AB - We examined whether apigenin affects the gene expression, secretion and activity of matrix metalloproteinase-3 (MMP-3) in primary cultured rabbit articular chondrocytes, as well as in vivo production of MMP-3 in the knee joint of rat to evaluate the potential chondroprotective effects of apigenin. Rabbit articular chondrocytes were cultured in a monolayer, and reverse transcription - polymerase chain reaction (RT-PCR) was used to measure interleukin-1beta (IL-1beta)-induced expression of MMP-3, MMP-1, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4), and ADAMTS-5. In rabbit articular chondrocytes, the effects of apigenin on IL-1beta-induced secretion and proteolytic activity of MMP-3 were investigated using western blot analysis and casein zymography, respectively. The effect of apigenin on MMP-3 protein production was also examined in vivo. In rabbit articular chondrocytes, apigenin inhibited the gene expression of MMP-3, MMP-1, MMP-13, ADAMTS-4, and ADAMTS-5. Furthermore, apigenin inhibited the secretion and proteolytic activity of MMP-3 in vitro, and inhibited production of MMP-3 protein in vivo. These results suggest that apigenin can regulate the gene expression, secretion, and activity of MMP-3, by directly acting on articular chondrocytes. PMID- 26902086 TI - Esculetin, a Coumarin Derivative, Inhibits Aldose Reductase Activity in vitro and Cataractogenesis in Galactose-Fed Rats. AB - Naturally occurring coumarin compounds have received substantial attention due to their pharmaceutical effects. Esculetin is a coumarin derivative and a polyphenol compound that is used in a variety of therapeutic and pharmacological strategies. However, its effect on aldose reductase activity remains poorly understood. In this study, the potential beneficialeffects of esculetin on lenticular aldose reductase were investigated in galactose-fed (GAL) rats, an animal model of sugar cataracts. Cataracts were induced in Sprague-Dawley (SD) rats via a 50% galactose diet for 2 weeks, and groups of GAL rats were orally treated with esculetin (10 or 50 mg/kg body weight). In vehicle-treated GAL rats, lens opacificationwas observed, and swelling and membrane rupture of the lens fibercells were increased. Additionally, aldose reductase was highly expressed in the lens epithelium and superficialcortical fibersduring cataract development in the GAL rats. Esculetin reduced rat lens aldose reductase (RLAR) activity in vitro, and esculetin treatment significanty inhibited lens opacity, as well as morphological alterations, such as swelling, vacuolation and liquefaction of lens fibers,via the inhibition of aldose reductase in the GAL rats. These results indicate that esculetin is a useful treatment for galactose-induced cataracts. PMID- 26902087 TI - Quercetin Directly Interacts with Vitamin D Receptor (VDR): Structural Implication of VDR Activation by Quercetin. AB - The vitamin D receptor (VDR) is a member of the nuclear receptor (NR) superfamily. The VDR binds to active vitamin D3 metabolites, which stimulates downstream transduction signaling involved in various physiological activities such as calcium homeostasis, bone mineralization, and cell differentiation. Quercetin is a widely distributed flavonoidin nature that is known to enhance transactivation of VDR target genes. However, the detailed molecular mechanism underlying VDR activation by quercetin is not well understood. We firstdemonstrated the interaction between quercetin and the VDR at the molecular level by using fluorecence quenching and saturation transfer difference (STD) NMR experiments. The dissociation constant (Kd) of quercetin and the VDR was 21.15 +/ 4.31 MUM, and the mapping of quercetin subsites for VDR binding was performed using STD-NMR. The binding mode of quercetin was investigated by a docking study combined with molecular dynamics (MD) simulation. Quercetin might serve as a scaffold for the development of VDR modulators with selective biological activities. PMID- 26902088 TI - The SLEEP GOAL as a success criteria in obstructive sleep apnea therapy. PMID- 26902089 TI - The water penetration of different ventilation tubes. AB - The insertion of middle ear ventilation tubes remains one of the most common procedures for ENT surgeons. A common concern amongst patients undergoing such procedures is the effect on their ability to partake in swimming and other water sports. Currently there is little evidence comparing the penetration ability of different water solutions encountered by swimmers. This study compares the water penetration of four different water solutions for Shah, mini-Shah, T tube and titanium bobbin ventilation tubes. A model was constructed to replicate a grommet inserted through a tympanic membrane using a syringe barrel, latex membrane and one of the ventilation tubes. Four solutions (sea water, chlorinated water, freshwater and soapy water) were then pipetted down the barrel until penetration of the tube occurred. The volume required for penetration was recorded. For all tubes soapy water was the most penetrating, followed by seawater. Titanium bobbins required significantly less of each solution for penetration. Mini-Shah grommets required significantly more of all solutions except soapy water for penetration to occur. Shah grommets were more resistant to chlorinated and sea water than T tubes. Mini-Shah grommets appear to protect against water penetration into the middle ear cleft and their use should be considered in patients who are keen water-sport enthusiasts. Furthermore, swimmers in sea or chlorinated water seem to be at higher risk than freshwater swimmers. Titanium bobbins were relatively easily penetrated by all four solutions and should be avoided in keen swimmers. PMID- 26902090 TI - Learning Curve for Laparoscopic Pancreaticoduodenectomy: a CUSUM Analysis. AB - BACKGROUND: Laparoscopic pancreaticoduodenectomy (LPD), an advanced minimally invasive technique, has demonstrated advantages to open pancreaticoduodenectomy (OPD). However, this complex procedure requires a relatively long training period to ensure technical proficiency. This study was therefore designed to analyze the learning curve for LPD. METHODS: From October 2010 to September 2015, 63 standard pancreaticoduodenectomy procedures were to be performed laparoscopically by a single surgeon at the Department of Pancreatic Surgery, West China Hospital, Sichuan University, China. After applying the inclusion and exclusion criteria, a total of 57 patients were included in the study. Data for all the patients, including preoperative, intraoperative, and postoperative variables, were prospectively collected and analyzed. The learning curve for LPD was evaluated using both cumulative sum (CUSUM) and risk-adjusted CUSUM (RA-CUSUM) methods. All of the variables among the learning curve phases were compared. RESULTS: Based on the CUSUM and the RA-CUSUM analyses, the learning curve for LPD was grouped into three phases: phase I was the initial learning period (cases 1-11), phase II represented the technical competence period (cases 12-38), and phase III was regarded as the challenging period (cases 39-57). The operative time, intraoperative blood loss, and postoperative ICU demand significantly decreased with the learning curve. More lymph nodes were collected after the initial learning period. There were no significant differences in terms of postoperative complications or the 30-day mortality among the three phases. More challenging cases were encountered in phase III. CONCLUSIONS: According to this study, the learning curve for LPD consisted of three phases. Conservatively, to attain technical competence for performing LPD, a minimum of 40 cases are required for laparoscopic surgeons with a degree of laparoscopic experience. PMID- 26902091 TI - Continued decline in hip fracture incidence in Norway: a NOREPOS study. AB - The previously reported decline in age-adjusted hip fracture rates in Norway during 1999-2008 continued after 2008. The annual number of hip fractures decreased in women and increased in men. INTRODUCTION: Norway has among the highest hip fracture incidence rates ever reported despite previously observed declining rates from 1999 through 2008. The aim of the present study was to investigate whether this downward trend continued through 2013, and to compare gender-specific trends in 5 year age-groups during three time periods: 1999-2003, 2004-2008, and 2009-2013. METHODS: All hip fractures (cervical, trochanteric, and sub-trochanteric) admitted to Norwegian hospitals were retrieved. Annual age standardized incidence rates of hip fracture per 10,000 person-years by gender were calculated for the period 1999-2013. Time trends were tested by age-adjusted Poisson regression. RESULTS: From 1999 through 2013 there were 140,136 hip fractures in persons aged 50 years and above. Age-adjusted hip fracture incidence rates declined by 20.4 % (95 % CI: 18.6-20.1) in women and 10.8 % (95 % CI: 7.8 13.8) in men, corresponding to an average annual age-adjusted decline of 1.5 % in women and 0.8 % in men. Except for the oldest men, hip fracture rates declined in all age-groups 70 years and older. The average annual number of fractures decreased in women (-0.3 %) and increased in men (+1.1 %). CONCLUSIONS: During the past 15 years, hip fracture rates have declined in Norway. The forecasted growing number of older individuals might, however, cause an increase in the absolute number of fractures, with a substantial societal economic and public health burden. PMID- 26902092 TI - The effect of two doses of dried plum on bone density and bone biomarkers in osteopenic postmenopausal women: a randomized, controlled trial. AB - Daily consumption of 50 g of dried plum (equivalent to 5-6 dried plums) for 6 months may be as effective as 100 g of dried plum in preventing bone loss in older, osteopenic postmenopausal women. To some extent, these results may be attributed to the inhibition of bone resorption with the concurrent maintenance of bone formation. INTRODUCTION: The objective of our current study was to examine the possible dose-dependent effects of dried plum in preventing bone loss in older osteopenic postmenopausal women. METHODS: Forty-eight osteopenic women (65-79 years old) were randomly assigned into one of three treatment groups for 6 months: (1) 50 g of dried plum; (2) 100 g of dried plum; and (3) control. Total body, hip, and lumbar bone mineral density (BMD) were evaluated at baseline and 6 months using dual-energy X-ray absorptiometry. Blood biomarkers including bone specific alkaline phosphatase (BAP), tartrate-resistant acid phosphatase (TRAP 5b), high-sensitivity C-reactive protein (hs-CRP), insulin-like growth factor-1 (IGF-1), and sclerostin were measured at baseline, 3 months, and 6 months. Osteoprotegerin (OPG), receptor activator of nuclear factor kappa-B ligand (RANKL), calcium, phosphorous, and vitamin D were measured at baseline and 6 months. RESULTS: Both doses of dried plum were able to prevent the loss of total body BMD compared with that of the control group (P < 0.05). TRAP-5b, a marker of bone resorption, decreased at 3 months and this was sustained at 6 months in both 50 and 100 g dried plum groups (P < 0.01 and P < 0.04, respectively). Although there were no significant changes in BAP for either of the dried plum groups, the BAP/TRAP-5b ratio was significantly (P < 0.05) greater at 6 months in both dried plum groups whereas there were no changes in the control group. CONCLUSIONS: These results confirm the ability of dried plum to prevent the loss of total body BMD in older osteopenic postmenopausal women and suggest that a lower dose of dried plum (i.e., 50 g) may be as effective as 100 g of dried plum in preventing bone loss in older, osteopenic postmenopausal women. This may be due, in part, to the ability of dried plums to inhibit bone resorption. This clinical trial was registered at ClinicalTrials.gov: NCT02325895 . PMID- 26902093 TI - Reduced Sirtuin1 expression at the femoral neck in women who sustained an osteoporotic hip fracture. AB - To investigate the role of Sirtuin1 in osteoporosis, Sirtuin1 was determined at the femoral neck in female patients undergoing hip operation for fractured hip or osteoarthritis. Reduced Sirtuin1 was found in osteoporotic patients. Pharmacologic activation of Sirtuin1 reduced sclerostin, an inhibitor of bone formation. Activation of Sirtuin1 may be a new direction to generate therapies for osteoporosis. INTRODUCTION: The aim of the study are to investigate the role of Sirtuin1 (Sirt1), an anti-aging factor and a player in age-associated diseases, in osteoporotic hip fractures, and test the hypothesis that Sirt1 is a negative regulator of sclerostin, a bone formation inhibitor, in human femoral bone marrow mesenchymal cells (BM-MSCs). METHODS: Sirt1 and sclerostin were determined by western blot in bone samples obtained intra-operatively from the inferior medial cortex of the femoral neck (calcar region) in female patients undergoing partial hip replacement for fractured neck of femur (N = 10) or hip replacement for osteoarthritis (N = 8) (mean +/- SD age 81 +/- 8.1 vs. 68 +/- 9.3 years; BMI 26.2 +/- 3.6 vs. 25.9 +/- 7.1 kg/m(2) in osteoporotic and osteoarthritis patients). Calcar thickness and femoral bone mineral density (BMD) were determined preoperatively by X-ray using a digital TraumaCad(TM) software and DEXA. Femoral BM-MSCs were collected intra-operatively and treated with SRT3025, a Sirt1 activator. Sclerostin and dentin matrix acidic phosphoprotein (DMP1) were determined by western blot and messenger RNA (mRNA) expression of Lef1 and DMP1 was evaluated by quantitative real-time PCR. RESULTS: Osteoporotic (OP) patients had reduced cortical thickness, femoral neck, and total hip BMD compared to osteoarthritis (OA) patients. Calcar Sirt1 expression was significantly reduced, while sclerostin was markedly increased in OP compared to OA patients. Sirt1 and sclersotin expressions were inversely correlated (r = 0.49, P = 0.047). SRT3025 administration down-regulated sclerostin and up regulated DMP1 protein level and increased LEF1 and DMP1 mRNA expressions in OP patient-derived BM-MSCs. CONCLUSIONS: Reduced femoral neck Sirt1 may play a role in osteoporotic hip fractures in part via influencing local sclerostin expression. The therapeutic potential of Sirt1 activation in osteoporosis warrants further investigation. PMID- 26902095 TI - Male-to-female transitions: Implications for occupational performance, health, and life satisfaction. AB - BACKGROUND: People who undergo a gender transition process experience changes in different everyday occupations. These changes may impact their health and life satisfaction. PURPOSE: This study examined the difference in the occupational performance history scales (occupational identity, competence, and settings) between male-to-female transgender women and cisgender women and the relation of these scales to health and life satisfaction. METHOD: Twenty-two transgender women and 22 matched cisgender women completed a demographic questionnaire and three reliable measures in this cross-sectional study. Data were analyzed using a two-way analysis of variance and multiple linear regressions. FINDINGS: The results indicate lower performance scores for the transgender women. In addition, occupational settings and group membership (transgender and cisgender groups) were found to be predictors of life satisfaction. IMPLICATIONS: The present study supports the role of occupational therapy in promoting occupational identity and competence of transgender women and giving special attention to their social and physical environment. PMID- 26902094 TI - Teriparatide for osteoporosis: importance of the full course. AB - Teriparatide (TPTD) is the only currently available therapeutic agent that increases the formation of new bone tissue and can provide some remediation of the architectural defects in the osteoporotic skeleton. The use of teriparatide clinically is limited to 24 months. We review clinical findings during daily teriparatide treatment over time. Teriparatide appears to increase bone formation more than bone resorption as determined biochemically and histologically. Teriparatide exerts its positive effects on bone formation in two distinct fashions. The first is direct stimulation of bone formation that occurs within active remodeling sites (remodeling-based bone formation) and on surfaces of bone previously inactive (modeling-based bone formation). The second is an increase in the initiation of new remodeling sites. Both processes contribute to the final increase in bone density observed by non-invasive tools such as DXA. Remodeling is the repair process by which skeletal tissue is maintained in a young healthy state, and when stimulated by TPTD is associated with a positive bone balance within each remodeling cavity. It seems likely therefore that this component will contribute to the anti-fracture efficacy of TPTD. Teriparatide reduces the risk of fracture, and this effect appears to increase with longer duration of therapy. The use of novel treatment regimens, including shorter courses, should be held in abeyance until controlled clinical trials are completed to define the relative fracture benefits of such approaches in comparison to the 24-month daily use of the agent. Summary In patients with osteoporosis at high risk for fracture, the full continuous 24-month course with teriparatide results in improved skeletal health and outcomes than shorter time periods. PMID- 26902097 TI - 'Zipbody' leucine zipper-fused Fab in E. coli in vitro and in vivo expression systems. AB - A small antibody fragment, fragment of antigen binding (Fab), is favorable for various immunological assays. However, production efficiency of active Fab in microorganisms depends considerably on the clones. In this study, leucine zipper peptide pairs that dimerize in parallel (ACID-p1 (LZA)/BASE-p1 (LZB) or c-Jun/c Fos) were fused to the C-terminus of heavy chain (Hc, VH-CH1) and light chain (Lc, VL-CL), respectively, to accelerate the association of Hc and Lc to form Fab in Escherichia coli in vivo and in vitro expression systems. The leucine zipper fused Fab named 'Zipbody' was constructed using anti-E. coli O157 monoclonal antibody obtained from mouse hybridoma and produced in both in vitro and in vivo expression systems in an active form, whereas Fab without the leucine zipper fusion was not. Similarly, Zipbody of rabbit monoclonal antibody produced in in vitro expression showed significant activity. The purified, mouse Zipbody produced in the E. coli strain Shuffle T7 Express had specificity toward the antigen; in bio-layer interferometry analysis, the KD value was measured to be 1.5-2.0 * 10(-8) M. These results indicate that leucine zipper fusion to Fab C termini markedly enhances active Fab formation in E. coli. PMID- 26902096 TI - Reduced soluble RAGE is associated with disease severity of axonal Guillain-Barre syndrome. AB - Soluble receptor for advanced glycation end products (sRAGE) is an anti inflammatory factor that mitigates the proinflammatory effects of high mobility group box 1 (HMGB1). The aim of this study was to investigate whether Guillain Barre syndrome (GBS)-related inflammation are mediated by sRAGE and HMGB1. We measured serum sRAGE, HMGB1, IL-6, and TNF-alpha levels in 86 patients with GBS and analysed associations between sRAGE or HMGB1 and clinical variables in these subjects. In addition, we determined cerebrospinal fluid sRAGE and HMGB1 levels in a cross-sectional study of 50 patients with GBS who had matched serum samples. We found serum sRAGE levels in patients with the acute motor axonal neuropathy (AMAN) subtype of GBS, but not other subtypes, were significantly lower than those in healthy controls, and were significantly correlated with GBS disability score and Erasmus GBS outcome score, while serum HMGB1, IL-6, and TNF-alpha levels in all subtypes of GBS were significantly higher than those in healthy controls. Moreover, increased sRAGE levels and decreased HMGB1 levels after treatment were observed. Our results showed that serum sRAGE may be a useful biomarker for inflammation in the AMAN GBS subtype, while HMGB1 may be related to the inflammatory process across all types of GBS. PMID- 26902098 TI - Investigation into the utility of an immunocytochemical assay in body cavity effusions for diagnosis of feline infectious peritonitis. AB - Objectives Feline coronaviruses (FCoVs) exist as two biotypes, feline enteric coronavirus and feline infectious peritonitis virus. Although feline infectious peritonitis (FIP) is a very common disease, the ante-mortem diagnosis of this disease still remains a challenge. Immunofluorescence staining of FCoV in macrophages in effusion has been considered as the reference standard for the diagnosis, but recently this method has been shown to have lower specificity than previously reported. In addition, this method is not widely available and requires the use of fluorescence microscopes. Therefore, it was the aim of this study to evaluate the diagnostic potential of an immunocytochemical (ICC) assay using body cavity effusion. Methods Effusion samples from 27 cats with immunohistochemically confirmed FIP and 29 cats with suspected FIP but a definitive diagnosis of another disease were examined. ICC specimens were evaluated with respect to positive immunostaining. In addition, effusion samples were stained with haematoxylin and eosin and evaluated cytologically. Results A diagnostic sensitivity of 85.2% was recorded for effusion specimens (95% confidence interval [CI] 66.3-95.8), while the diagnostic specificity was only 72.4% (95% CI 52.8-87.3). Conclusions and relevance Once the clinical disease of FIP develops in a cat, it always leads to death, and most of the cats are euthanased within a few days or weeks. As false-positive results might lead to euthanasia of cats suffering from potentially treatable diseases, the diagnostic specificity of a diagnostic tool is the most important factor in a fatal disease like FIP. Thus, the diagnostic utility of this test proved to be insufficient and positive ICC results should be interpreted with caution. Nevertheless, full-body necropsy could not be performed in 13/29 control cats. It is possible that these cats actually suffered from early-stage FIP and that this fact might have influenced the diagnostic specificity of the ICC. Based on the results of the present study, however, ICC of effusion samples currently cannot be recommended to confirm a suspicion of FIP. PMID- 26902099 TI - Issues promoting and hindering girls' well-being in Northern Finland. AB - Well-being is a complex concept that includes elements of inequality due to socio economics, living environment or gender. Every person also encounters unique situations and has different experiences of well-being. This qualitative study aims to describe what issues promote and hinder the well-being of girls aged 13 16 in Northern Finland. A total of 117 girls aged 13-16 living in Northern Finland were asked to write about the issues that hinder and promote their well being. The girls' responses were analysed using content analysis. After analysis, two combining categories were discovered: issues hindering well-being were a debilitating sphere of life and negative experiences in life, and issues promoting well-being were positive subjective sensations and favourably perceived conditions. The results of this study indicate that girls' well-being is connected to their social and physical environment. As the girls' view of the issues that promote or hinder health are connected and interact with their living environment, there is also a need for health promotion measures to take into account both the individuals and the environment in which they function and live. This view challenges us to see health promotion in a broader way-a way which takes into account structural and political factors, individual consultation and empowerment. PMID- 26902101 TI - Report of a rare case of atypical lymphoplasmacyte-rich meningioma in the tentorium mimicking idiopathic hypertrophic pachymeningitis. AB - A lymphoplasmacyte-rich meningioma (LPRM) is an extremely rare variant of meningioma. Here, we report a case of atypical LPRM with increased mitosis in a 55-year-old man. Preoperative magnetic resonance imaging suggested meningioma with brain invasion in the left tentorium cerebelli. Histological examination revealed sclerotic fibrosis and dense lymphoplasmacytic infiltration; based on these findings, the differential diagnosis included LPRM and fibroinflammatory lesions of the dura, such as idiopathic hypertrophic pachymeningitis (IHP), IgG4 related disease (IgG4-RD), and Rosai-Dorfman disease. Epithelial membrane antigen (EMA) immunostaining highlighted sheets of meningothelial cells, which strongly supported the diagnosis of meningioma. Although brain invasion was suspected in radiologic image, no histologic evidence of brain invasion was found. However, the mitoses were observed to be 8/10 high power fields, along with increased Ki 67 labeling index with focal spontaneous necrosis, and the final pathologic diagnosis was atypical LPRM. IgG4-RD was ruled out, because IgG4 counts and the IgG4:IgG ratio of plasma cells did not meet the diagnostic criteria for IgG4-RD. To date, only one case of LPRM with brain invasion has been reported as atypical LPRM. This case is therefore the second case of atypical LPRM with increased mitosis that histologically mimicked IHP. PMID- 26902102 TI - Quantification of Age-Related Tissue-Level Failure Strains of Rat Femoral Cortical Bones Using an Approach Combining Macrocompressive Test and Microfinite Element Analysis. AB - Bone mechanical properties vary with age; meanwhile, a close relationship exists among bone mechanical properties at different levels. Therefore, conducting multilevel analyses for bone structures with different ages are necessary to elucidate the effects of aging on bone mechanical properties at different levels. In this study, an approach that combined microfinite element (micro-FE) analysis and macrocompressive test was established to simulate the failure of male rat femoral cortical bone. Micro-FE analyses were primarily performed for rat cortical bones with different ages to simulate their failure processes under compressive load. Tissue-level failure strains in tension and compression of these cortical bones were then back-calculated by fitting the experimental stress strain curves. Thus, tissue-level failure strains of rat femoral cortical bones with different ages were quantified. The tissue-level failure strain exhibited a biphasic behavior with age: in the period of skeletal maturity (1-7 months of age), the failure strain gradually increased; when the rat exceeded 7 months of age, the failure strain sharply decreased. In the period of skeletal maturity, both the macro- and tissue-levels mechanical properties showed a large promotion. In the period of skeletal aging (9-15 months of age), the tissue-level mechanical properties sharply deteriorated; however, the macromechanical properties only slightly deteriorated. The age-related changes in tissue-level failure strain were revealed through the analysis of male rat femoral cortical bones with different ages, which provided a theoretical basis to understand the relationship between rat cortical bone mechanical properties at macro- and tissue-levels and decrease of bone strength with age. PMID- 26902100 TI - In situ validation of VEGFR-2 and alpha v beta 3 integrin as targets for breast lesion characterization. AB - Vascular endothelial growth factor receptor 2 (VEGFR-2) and alpha v beta 3 integrin are the most frequently addressed targets in molecular imaging of tumor angiogenesis. In preclinical studies, molecular imaging of angiogenesis has shown potential to detect and differentiate benign and malignant lesions of the breast. Thus, in this retrospective clinical study employing patient tissues, the diagnostic value of VEGFR-2, alpha v beta 3 integrin and vascular area fraction for the diagnosis and differentiation of breast neoplasia was evaluated. To this end, tissue sections of breast cancer (n = 40), pre-invasive ductal carcinoma in situ (DCIS; n = 8), fibroadenoma (n = 40), radial scar (n = 6) and normal breast tissue (n = 40) were used to quantify (1) endothelial VEGFR-2, (2) endothelial alpha v beta 3 integrin and (3) total alpha v beta 3 integrin expression, as well as (4) the vascular area fraction. Sensitivity and specificity to differentiate benign from malignant lesions were calculated for each marker by receiver operating characteristics (ROC) analyses. Whereas vessel density, as commonly used, did not significantly differ between benign and malignant lesions (AUROC: 0.54), VEGFR-2 and alpha v beta 3 integrin levels were gradually up-regulated in carcinoma versus fibroadenoma versus healthy tissue. The highest diagnostic accuracy for differentiating carcinoma from fibroadenoma was found for total alpha v beta 3 integrin expression (AUROC: 0.76), followed by VEGFR-2 (AUROC: 0.71) and endothelial alpha v beta 3 integrin expression (AUROC: 0.68). In conclusion, total alpha v beta 3 integrin expression is the best discriminator between breast cancer, fibroadenoma and normal breast tissue. With respect to vascular targeting and molecular imaging of angiogenesis, endothelial VEGFR-2 appeared to be slightly superior to endothelial alpha v beta 3 for differentiating benign from cancerous lesions. PMID- 26902103 TI - Performance perceptions and self-focused attention predict post-event processing after a real-life social performance situation. AB - BACKGROUND AND OBJECTIVES: Cognitive approaches to social anxiety suggest that an excessive brooding about one's performance in a social situation (post-event processing; PEP) is involved in the maintenance of anxiety. To date, most studies investigating PEP were conducted in laboratory settings. The present study sought to replicate previous findings on predictors of PEP after a naturalistic social performance situation. METHODS: Sixty-five students, who had to give an evaluated presentation for credits, completed measures of trait social anxiety. Immediately after their presentation, participants rated state anxiety and attentional focus during the presentation, and provided an overall evaluation of their performance. One week after the presentation, they rated PEP during the preceding week, and reappraised their performance. RESULTS: Regression analyses demonstrated that the performance ratings after and self-focused attention during the presentation were unique predictors of PEP over and above the effects of trait and state anxiety. There was no evidence that PEP was associated with a biased recall of individual performance evaluations. CONCLUSIONS: The results support cognitive theories that emphasize the importance of negative self-perceptions in the development of social anxiety and related processes, and underline self-focused attention and self-evaluative processes as important targets during treatment. PMID- 26902104 TI - Colocutaneous fistula: a rare postoperative complication after surgical treatment of an irreducible left inguinal hernia Case Report. AB - AIM: The colo-cutaneous fistula is an extremely rare post-operative complication of hernias. This type of complication, besides the surgical aspects, raises also a medical-legal problem regarding the production of the fistula and its consequences. CASE REPORT: The authors present the clinical case of a 65 years old man, J.N., from a rural background, who presented himself in the ambulatory with a colo-cutaneous fistula as a complication which debuted a few weeks after a surgical intervention for an irreducible left inguinal hernia. He was submitted to a surgical reintervention with good results. DISCUSSION: The main particularity of the present case is the association of the colo-cutaneous fistula with the presence of the oxyuris helmintiasis in the fistulos secretions. CONCLUSIONS: Even though it was rather difficult to obtain the patient's consent for the surgical treatment, the intervention had very good results leading to the healing of the patient. KEY WORDS: Colo-cutaneous fistula, Enterobius vermicularis (oxyuris helmintiasis), Post-operative complications of hernia. PMID- 26902105 TI - Carotid artery stenting is as effective as carotid endarterectomy, study shows. PMID- 26902106 TI - Infants Understand Others' Needs. AB - Infants begin to help other individuals in the second year of life. However, it is still unclear whether early helping behavior is based on an understanding of other individuals' needs and is thus motivated prosocially. In the present eye tracking study, 9- to 18-month-old infants (N= 71) saw a character in need of help, unable to reach its goal because of an obstacle, and a second character that was able to achieve a goal on its own. When a third individual (a helper) initiated an action, the infants expected the helper to help the character in need (as indicated during the anticipatory-looking and violation-of-expectation phases). Their prosocial understanding did not differ between age groups and was not related to their helping behavior (measured in two behavioral tasks). Thus, infants understand other individuals' needs even before they start to help others themselves. This indicates that early helping may indeed be motivated prosocially and raises the question of which other competences underlie the ontogeny of helping behavior. PMID- 26902107 TI - Summaries for Patients. Oral Prednisolone in the Treatment of Acute Gout. PMID- 26902108 TI - Coxsackievirus A16-like particles produced in Pichia pastoris elicit high-titer neutralizing antibodies and confer protection against lethal viral challenge in mice. AB - Coxsackievirus A16 (CA16) is a major causative agent of hand, foot and mouse disease (HFMD) which has been affecting millions of young children annually in the Asia-Pacific region over the last seven years. However, no commercial CA16 vaccines are currently available. In the present study, we investigated the expression of virus-like particles (VLPs) of CA16 in Pichia pastoris yeast and their immunogenicity and protective efficacy in mice. We found that CA16-VLPs could be produced at relatively high levels in P. pastoris yeast transformed with a construct co-expressing the P1 and 3CD proteins of CA16. Mice immunized with the yeast-derived CA16-VLPs produced high-titer serum antibodies with potent neutralization effect specifically on CA16. More importantly, passive immunization with the yeast-derived VLPs fully protected neonatal mice against CA16 lethal challenge in both antisera transfer and maternal immunization experiments. Collectively, our results demonstrate that P. pastoris-derived CA16 VLPs represent a promising CA16 vaccine candidate with proven preclinical efficacy and desirable traits for manufacturing at industrial scale. PMID- 26902109 TI - Factors involved in continuance of atazanavir-based regimens: Results from a cohort of HIV1-positive patients. AB - We evaluated predictive factors involved in durability and therapeutic failure of atazanavir (ATV)-based antiretroviral regimens with or without ritonavir (r) in real life setting. This retrospective study of HIV-1-positive patients evaluated the factors related to ATV continuance and the time-dependent probability of therapeutic failure (HIV-RNA >200 copies/mL and concomitant discontinuation of ATV). We also investigated the rate of therapeutic failure and the variations in total bilirubin levels from starting unboosted ATV-based regimens. The study involved 1030 patients: 183 treatment-naive patients (17.8%) started ATV/r (17 subsequently switched to unboosted ATV); 653 (63.4%) switched to ATV/r from previous antiretroviral regimens (121 subsequently switched to unboosted ATV); and 194 (18.8%) switched to unboosted ATV from previous ATV-free regimens. The median ATV follow-up was 28 months (interquartile range 7-56). The risk of ATV discontinuation was significantly lower in patients switched to unboosted ATV from ATV/r (HR 0.45; p < 0.0001). The discontinuation of ATV correlated with female gender (HR 1.26; p = 0.035), use of a zidovudine/didanosine/stavudine containing backbone (HR 1.8; p = 0.004), and a baseline CD4+ cell counts of <200/MUL (HR 1.54; p = 0.003), the last of which was also associated with a higher risk of therapeutic failure (HR 2.42; p = 0.001). Total bilirubin levels were significantly lower in the patients switching from ATV/r to unboosted ATV. Unboosted ATV-based therapies are safe and effective options in patients whose immuno-virological conditions are stable, and allow the long-term survival of ATV containing regimens. PMID- 26902110 TI - Acid production and conversion of konjac glucomannan during in vitro colonic fermentation affected by exogenous microorganisms and tea polyphenols. AB - Impacts of exogenous microorganisms and tea polyphenols on acid production and conversion during in vitro colonic fermentation of konjac glucomannan (KGM) were assessed in this study. Colonic fermentation of KGM by the fecal extract of healthy adults resulted in a propionate-rich profile, as acetic, propionic, butyric and lactic acids production were 16.1, 13.0, 3.3 and 20.2 mmol/L, respectively. Inoculation of one of ten exogenous microorganisms in the fermentative systems increased acetic, propionic and butyric acids production by 50-230%, 9-190% and 110-350%, respectively, and also accelerated lactic acid conversion by 14-40%. Tea polyphenols in the fermentative systems showed clear inhibition on both acid production and conversion; however, this inhibition could be partially or mostly antagonised by the inoculated exogenous microorganisms, resulting in improved acid production and conversion. In total, Lactobacillus brevis and Sterptococcus thermophilus were more able to increase acid production, and the propionate-rich profile was not changed in all cases. PMID- 26902112 TI - Lens placode planar cell polarity is dependent on Cdc42-mediated junctional contraction inhibition. AB - Development of the ocular lens commences with the formation of the lens placode, an epithelial structure that thickens and subsequently bends inward in a process called invagination. Invagination is observed during the development of many embryonic structures, but the spectrum of morphogenetic events driving this process are, in most cases, not fully understood. A characteristic commonly found in embryonic tissues undergoing epithelial reorganization is planar polarity, a property where cells are geometrically and/or molecularly orientated in a specific direction along the plane of an epithelium. Planar polarity is known to drive the morphogenesis of several epithelial structures, however its role during invagination events is less clear. We have found that at the onset of invagination, cells of the lens placode become geometrically planar polarized such that they are orientated toward a central point in the lens placode. Further investigation revealed that this is due to contraction of radially orientated junctions and the elongation of those circumferentially orientated. Radial junctions have an elevated localization of actomyosin and their contraction is dependent on the F-actin and Rho-kinase binding protein, Shroom3. Elongation of circumferential junctions is dependent upon Cdc42, a Rho-GTPase known to regulate polarity via the Par-complex. We determined that Cdc42 and members of the Par complex inhibit Shroom3-induced contractility and promote anisotropic placode cell geometry through inhibition of junctional contraction. We postulate that invagination of the lens placode requires careful orchestration of these opposing processes which are mediated by the planar polarization of junctional proteins. PMID- 26902113 TI - Functional impairment of endothelial cells by the antimycotic amphotericin B. AB - We set out to determine the membrane potential (Vm) of the endothelial cell line EA.hy926 and its sensitivity to the antimycotic amphotericin B (AmB), a commonly used antifungal component in cell culture media. We measured the endothelial Vm under various experimental conditions by patch clamp technique and found that Vm of AmB-treated cells is (-12.1 +/- 9.3) mV, while in AmB-untreated (control) cells it is (-57.1 +/- 4.1) mV. In AmB-free extracellular solutions, Vm recovered toward control levels and this gain in Vm rapidly dissipated upon re-addition of AmB, demonstrating a rapid and reversible effect of AmB on endothelial Vm. The consequences of AmB dependent alterations in endothelial transmembrane potential were tested at the levels of Ca(2+) signaling, of nucleotide concentrations, and energy metabolism. In AmB-treated cells we found substantially reduced Ca(2+) entry (to about 60% of that in control cells) in response to histamine induced endoplasmic reticulum (ER) Ca(2+) depletion, and diminished the ATP-to-ADP ratio (by >30%). Our data demonstrate a marked and experimentally relevant dependence of basic functional parameters of cultured endothelial cells on the presence of the ionophoric antimycotic AmB. The profound and reversible effects of the widely used culture media component AmB need careful consideration when interpreting experimental data obtained under respective culture conditions. PMID- 26902111 TI - miR-8 modulates cytoskeletal regulators to influence cell survival and epithelial organization in Drosophila wings. AB - The miR-200 microRNA family plays important tumor suppressive roles. The sole Drosophila miR-200 ortholog, miR-8 plays conserved roles in Wingless, Notch and Insulin signaling - pathways linked to tumorigenesis, yet homozygous null animals are viable and often appear morphologically normal. We observed that wing tissues mosaic for miR-8 levels by genetic loss or gain of function exhibited patterns of cell death consistent with a role for miR-8 in modulating cell survival in vivo. Here we show that miR-8 levels impact several actin cytoskeletal regulators that can affect cell survival and epithelial organization. We show that loss of miR-8 can confer resistance to apoptosis independent of an epithelial to mesenchymal transition while the persistence of cells expressing high levels of miR-8 in the wing epithelium leads to increased JNK signaling, aberrant expression of extracellular matrix remodeling proteins and disruption of proper wing epithelial organization. Altogether our results suggest that very low as well as very high levels of miR-8 can contribute to hallmarks associated with cancer, suggesting approaches to increase miR-200 microRNAs in cancer treatment should be moderate. PMID- 26902114 TI - Smooth muscle origin of postnatal 2nd CVP is pre-determined in early embryo. AB - Recent identification of the neonatal 2nd coronary vascular population (2nd CVP) suggests that a subset of these vessels form de novo and mature in the inner myocardial wall of the postnatal heart. However, the origin of smooth muscle cells (SMCs) in the postnatal 2nd CVP remains undetermined. Using a tamoxifen inducible Wt1-CreER driver and a Rosa26-RFP reporter line, we traced the lineage of epicardial cells to determine if they contribute to SMCs of the 2nd CVP. Late embryonic and postnatal induction of Wt1-CreER activity demonstrated that at these stages Wt1-labeled epicardium does not significantly migrate into the myocardium to form SMCs. However, following tamoxifen treatment at an early embryonic stage (E10.5), we detected Wt1 descendants (epicardium-derived cells, or EPDCs) in the outer myocardial wall at E17.5. When the 2nd CVP forms and remodels at postnatal stage, these early labeled EDPCs re-migrate deep into the inner myocardial wall and contribute to 2nd CVP-SMCs in the adult heart. Our findings reveal that SMCs in the postnatal 2nd CVP are pre-specified as EPDCs from the earliest wave of epicardial cell migration. Rather than the re activation and migration of epicardial cells at later stages, these resident EPDCs mobilize and contribute to smooth muscle of the 2nd CVP during postnatal development. PMID- 26902115 TI - TET1 contributes to neurogenesis onset time during fetal brain development in mice. AB - Epigenetic mechanisms are relevant to development and contribute to fetal neurogenesis. DNA methylation and demethylation contribute to neural gene expression during mouse brain development. Ten-eleven translocation 1 (TET1) regulates DNA demethylation by converting 5-methylcytosine (5mC) to 5 hydroxymethylcytosine (5hmC). TET1 specifically regulates 5hmC in the central nervous system (CNS), including during neurogenesis in the adult brain. However little is known about its function in fetal neurogenesis. In order to evaluate the role of TET1 in fetal brain development, we generated TET1-overexpressing transgenic (TG) mice. TET1 overexpression was confirmed in the brains of fetal mice, and we detected 5hmC overexpression in the TG brains compared to that in the wild type (WT) brains, using a dot-blot assay. In order to observe the role of TET1 in fetal brain development, we examined fetal brain samples at varied time points by using real-time PCR, Western blotting, and Immunofluorescence (IF). We confirmed that TET1 contributes to neurogenesis by upregulating the protein expressions of neuronal markers in the TG mouse brains, as determined by Western blotting. However the cortex structure or brain mass between WT and TG mice showed no significant difference by IF. In conclusion, TET1 makes the start time of neurogenesis earlier in the TG brains compared to that in the WT brains during fetal brain development. PMID- 26902116 TI - Development of exosome surface display technology in living human cells. AB - Surface display technology is an emerging key player in presenting functional proteins for targeted drug delivery and therapy. Although a number of technologies exist, a desirable mammalian surface display system is lacking. Exosomes are extracellular vesicles that facilitate cell-cell communication and can be engineered as nano-shuttles for cell-specific delivery. In this study, we report the development of a novel exosome surface display technology by exploiting mammalian cell secreted nano-vesicles and their trans-membrane protein tetraspanins. By constructing a set of fluorescent reporters for both the inner and outer surface display on exosomes at two selected sites of tetraspanins, we demonstrated the successful exosomal display via gene transfection and monitoring fluorescence in vivo. We subsequently validated our system by demonstrating the expected intracellular partitioning of reporter protein into sub-cellular compartments and secretion of exosomes from human HEK293 cells. Lastly, we established the stable engineered cells to harness the ability of this robust system for continuous production, secretion, and uptake of displayed exosomes with minimal impact on human cell biology. In sum, our work paved the way for potential applications of exosome, including exosome tracking and imaging, targeted drug delivery, as well as exosome-mediated vaccine and therapy. PMID- 26902117 TI - Overexpression of FOXO1 ameliorates the podocyte epithelial-mesenchymal transition induced by high glucose in vitro and in vivo. AB - Accumulating evidence has suggested that the epithelial-mesenchymal transition (EMT) is a pathway that potentially leads to podocyte depletion and proteinuria in diabetic nephropathy (DN). Therefore, this study was designed to investigate the protective effects of forkhead transcription factor O1 (FOXO1) on podocyte EMT, under high-glucose (HG) conditions in vitro and under diabetic conditions in vivo. The results showed that HG-induced podocyte EMT was associated with FOXO1 inactivation, which was accompanied by activation of the transforming growth factor (TGF)-beta1/SMAD3/integrin-linked kinase (ILK) pathway. Accordingly, constitutive FOXO1 activation suppressed the TGF-beta1/Smad3/ILK pathway and partially reversed EMT, similar to the effects observed after treatment with SIS3 or QLT0267, which are selective inhibitors of TGF-beta1-dependent SMAD3 phosphorylation and ILK, respectively. In addition, lentiviral-mediated FOXO1 overexpression in the kidneys of diabetic mice considerably increased FOXO1 expression and activation, while decreasing proteinuria and renal pathological injury. These data suggested that forced FOXO1 activation inhibited HG-induced podocyte EMT and ameliorated proteinuria and renal injury in diabetic mice. Our findings further highlighted that FOXO1 played a protective role against diabetes in mice and may potentially be used as a novel therapeutic target for treating diabetic nephropathy. PMID- 26902118 TI - Structure and mapping of spontaneous mutational sites of PyrR from Mycobacterium tuberculosis. AB - The emergence of resistant Mycobacterium tuberculosis (Mtb) infection and the dearth of drugs against tuberculosis have made it imperative to identify and validate novel targets and classes of drugs for treatment. The pyrimidine operon regulatory protein (PyrR), a regulator of de novo pyrimidine synthesis, is an essential enzyme and a probable 5-fluorouracil (5-FU) target in Mtb, with mutations in PyrR attributable to 5-FU resistance. Here we report, for the first time, the co-crystal structure of the PyrR-5-FU complex along with mapping of spontaneous mutational sites of PyrR. A cluster of mutations in the presence of the drug usually indicates a plausible region of drug-target interaction. Notably, we observed that three of the mutated PyrR residues lie in close proximity to the 5-FU binding site, including the amino acid Val178, which is involved in water mediated hydrogen bonding contact with 5-FU. Computational modeling of the PyrR-5'-phosphoribosyl-alpha-1'-pyrophosphate (PRPP) complex revealed the location of several other mutations at the PRPP binding site of PyrR, indicating their probable role in resistance. Indeed, 5-FU-resistant strains harboring these mutations exhibited decreased susceptibility to 5-FU. Considering that pyrimidine analogs are predominantly regarded to inhibit PyrR, the present studies will be beneficial for the screening of appropriate inhibitors of PyrR and help provide insight into future TB drug design and development. PMID- 26902119 TI - Lifespan and reproduction in brain-specific miR-29-knockdown mouse. AB - The microRNA miR-29 is widely distributed and highly expressed in adult mouse brain during the mouse's lifetime. We recently created conditional mutant mice whose miR-29 was brain-specifically knocked down through overexpression of an antisense RNA transgene against miR-29. To explore a role for brain miR-29 in maximizing organismal fitness, we assessed somatic growth, reproduction, and lifespan in the miR-29-knockdown (KD) mice and their wild-type (WT) littermates. The KD mice were developmentally indistinguishable from WT mice with respect to gross morphology and physical activity. Fertility testing revealed that KD males were subfertile, whereas KD females were hyperfertile, only in terms of reproductive success, when compared to their gender-matched WT correspondents. Another phenotypic difference between KD and WT animals appeared in their lifespan data; KD males displayed an overall increasing tendency in post reproductive survival relative to WT males. In contrast, KD females were prone to shorter lifespans than WT females. These results clarify that brain-targeted miR 29 knockdown affects both lifespan and reproduction in a gender-dependent manner, and moreover that the reciprocal responsiveness to the miR-29 knockdown between these two phenotypes in both genders closely follow life-course models based on the classical trade-off prediction wherein elaborate early-life energetic investment in reproduction entails accelerated late-life declines in survival, and vice versa. Thus, this study identified miR-29 as the first mammalian miRNA that is directly implicated in the lifetime trade-off between the two major fitness components, lifespan and reproduction. PMID- 26902120 TI - miR-130b targets NKD2 and regulates the Wnt signaling to promote proliferation and inhibit apoptosis in osteosarcoma cells. AB - miR-130b was significantly up-regulated in osteosarcoma (OS) cells. Naked cuticle homolog 2 (NKD2) inhibited tumor growth and metastasis in OS by suppressing Wnt signaling. We used three miRNA target analysis tools to identify potential targets of miR-130b, and found that NKD2 is a potential target of miR-130b. Based on these findings, we hypothesize that miR-130b might target NKD2 and regulate the Wnt signaling to promote OS growth. We detected the expression of miR-130b and NKD2 mRNA and protein by quantitative Real-Time PCR (qRT-PCR) and western blot assays, respectively, and found up-regulation of miR-130b and down regulation of NKD2 mRNA and protein exist in OS cell lines. MTT and flow cytometry assays showed that miR-130b inhibitors inhibit proliferation and promote apoptosis in OS cells. Furthermore, we showed that NKD2 is a direct target of miR-130b, and miR-130b regulated proliferation and apoptosis of OS cells by targeting NKD2. We further investigated whether miR-130b and NKD2 regulate OS cell proliferation and apoptosis by inhibiting Wnt signaling, and the results confirmed our speculation that miR-130b targets NKD2 and regulates the Wnt signaling to promote proliferation and inhibit apoptosis of OS cells. These findings will offer new clues for OS development and progression, and novel potential therapeutic targets for OS. PMID- 26902121 TI - Repositioning of antibiotic levofloxacin as a mitochondrial biogenesis inhibitor to target breast cancer. AB - Targeting mitochondrial biogenesis has become a potential therapeutic strategy in cancer due to their unique metabolic dependencies. In this study, we show that levofloxacin, a FDA-approved antibiotic, is an attractive candidate for breast cancer treatment. This is achieved by the inhibition of proliferation and induction of apoptosis in a panel of breast cancer cell lines while sparing normal breast cells. It also acts synergistically with conventional chemo drug in two independent in vivo breast xenograft mouse models. Importantly, levofloxacin inhibits mitochondrial biogenesis as shown by the decreased level of mitochondrial respiration, membrane potential and ATP. In addition, the anti proliferative and pro-apoptotic effects of levofloxacin are reversed by acetyl-L Carnitine (ALCAR, a mitochondrial fuel), confirming that levofloxacin's action in breast cancer cells is through inhibition of mitochondrial biogenesis. A consequence of mitochondrial biogenesis inhibition by levofloxacin in breast cancer cells is the deactivation of PI3K/Akt/mTOR and MAPK/ERK pathways. We further demonstrate that breast cancer cells have increased mitochondrial biogenesis than normal breast cells, and this explains their different sensitivity to levofloxacin. Our work suggest that levofloxacin is a useful addition to breast cancer treatment. Our work also establish the essential role of mitochondrial biogenesis on the activation of PI3K/Akt/mTOR and MAPK/ERK pathways in breast cancer cells. PMID- 26902122 TI - High-energy X-ray focusing and applications to pair distribution function investigation of Pt and Au nanoparticles at high pressures. AB - We report development of micro-focusing optics for high-energy x-rays by combining a sagittally bent Laue crystal monchromator with Kirkpatrick-Baez (K-B) X-ray focusing mirrors. The optical system is able to provide a clean, high-flux X-ray beam suitable for pair distribution function (PDF) measurements at high pressure using a diamond anvil cell (DAC). A focused beam of moderate size (10-15 MUm) has been achieved at energies of 66 and 81 keV. PDF data for nanocrystalline platinum (n-Pt) were collected at 12.5 GPa with a single 5 s X-ray exposure, showing that the in-situ compression, decompression, and relaxation behavior of samples in the DAC can be investigated with this technique. PDFs of n-Pt and nano Au (n-Au) under quasi-hydrostatic loading to as high as 71 GPa indicate the existence of substantial reduction of grain or domain size for Pt and Au nanoparticles at pressures below 10 GPa. The coupling of sagittally bent Laue crystals with K-B mirrors provides a useful means to focus high-energy synchrotron X-rays from a bending magnet or wiggler source. PMID- 26902124 TI - Modeling Chemotherapy-Induced Hair Loss: From Experimental Propositions toward Clinical Reality. AB - Chemotherapy-induced hair loss is one of the most devastating side effects of cancer treatment. To study the effects of chemotherapeutic agents on the hair follicle, a number of experimental models have been proposed. Yoon et al. report that transplantation of human scalp hair follicles onto chemotherapy-treated immunodeficient mice serves as an excellent in vivo model for chemotherapy induced hair loss. Yoon et al. demonstrate that (i) the response of human hair follicles grafted onto immunodeficient mice to cyclophosphamide resembles the key features of the chemotherapy-induced hair loss seen in patients with cancer and (ii) this human in vivo model for chemotherapy-induced hair loss is closer to clinical reality than to any earlier models. Undoubtedly, this model will serve as a valuable tool for analyses of the mechanisms that underlie this devastating side effect of anti-cancer therapy. PMID- 26902123 TI - Research Progress in Pseudoxanthoma Elasticum and Related Ectopic Mineralization Disorders. AB - Heritable ectopic mineralization disorders represent a phenotypically diverse group of conditions characterized by deposition of calcium phosphate complexes in soft connective tissues. The prototype of such conditions is pseudoxanthoma elasticum, and related conditions with overlapping clinical features include generalized arterial calcification of infancy and arterial calcification due to CD73 deficiency. Molecular genetic investigations have revealed mutations in the genes physiologically involved in generation of inorganic pyrophosphate and inorganic phosphate, and the findings suggest a unifying pathomechanism relating to reduced inorganic pyrophosphate/inorganic phosphate ratio. This hypothesis is based on the notion that inorganic pyrophosphate serves as a powerful inhibitor of mineralization, whereas inorganic phosphate is a promineralization factor, and an appropriate inorganic pyrophosphate/inorganic phosphate ratio is critical for prevention of ectopic mineralization under homeostatic conditions. PMID- 26902125 TI - Staphylococcus epidermidis Sets Things Right Again. AB - Commensal cutaneous bacteria are believed to play a role in skin homeostasis, possibly by counteracting the effects of pathogenic inflammation. In this issue, Xia et al. show that Staphylococcus epidermidis is involved in the regulation of Propionibacterium acnes-induced inflammation. Staphylococcal lipoteichoic acid induces miR-143, which in turn inhibits toll-like receptor 2 mRNA to decrease toll-like receptor 2 protein and consequently suppresses P. acnes-induced proinflammatory cytokines. PMID- 26902126 TI - Too Much, Too Little or Just Enough: A Goldilocks Effect for IL-13 and Skin Barrier Regulation? AB - The mechanistic relationship between IL-4/IL-13 and skin barrier function has been of interest since the filaggrin discovery and the subsequent in vitro demonstration that IL-4 and IL-13 downregulate filaggrin expression in cultured keratinocytes. Honzke and colleagues explore these interactions further. The effects of IL-4/ll-13 may be context dependent, with differing roles in homeostasis and in disease. PMID- 26902127 TI - Seborrheic Keratoses: The Rodney Dangerfield of Skin lesions, and Why They Should Get Our Respect. AB - Neel et al. have demonstrated that seborrheic keratosis, the most common of all skin tumors, is dependent on acutely transforming retrovirus AKT8 in rodent T cell lymphoma signaling. The authors found that these lesions are hypersensitive to Akt inhibitors which bind to the ATP binding site of Akt. Cutaneous squamous cell carcinoma is resistant to Akt inhibitors. The implications of this study are not limited to seborrheic keratosis. The presence of wild type p53 (seborrheic keratosis) or mutant p53 (cutaneous squamous cell carcinoma) appears to dictate whether a lesion is sensitive to Akt inhibition or not. PMID- 26902128 TI - Research Techniques Made Simple: Bacterial 16S Ribosomal RNA Gene Sequencing in Cutaneous Research. AB - Skin serves as a protective barrier and also harbors numerous microorganisms collectively comprising the skin microbiome. As a result of recent advances in sequencing (next-generation sequencing), our understanding of microbial communities on skin has advanced substantially. In particular, the 16S ribosomal RNA gene sequencing technique has played an important role in efforts to identify the global communities of bacteria in healthy individuals and patients with various disorders in multiple topographical regions over the skin surface. Here, we describe basic principles, study design, and a workflow of 16S ribosomal RNA gene sequencing methodology, primarily for investigators who are not familiar with this approach. This article will also discuss some applications and challenges of 16S ribosomal RNA sequencing as well as directions for future development. PMID- 26902130 TI - Short and long-term post-operative outcomes of duodenum preserving pancreatic head resection for chronic pancreatitis affecting the head of pancreas: a systematic review and meta-analysis. AB - BACKGROUND: To evaluate the short and long term outcomes of duodenum preserving pancreatic head resection (DPPHR) procedures in the treatment of painful chronic pancreatitis. METHODS: A systematic literature search was performed to identify all comparative studies evaluating long and short term postoperative outcomes (pain relief, morbidity and mortality, pancreatic exocrine and endocrine function). RESULTS: Five published studies fulfilled the inclusion criteria including 1 randomized controlled trial comparing the Beger and Frey procedure. In total, 323 patients underwent surgical procedures for chronic pancreatitis, including Beger (n = 138) and Frey (n = 99), minimal Frey (n = 32), modified Frey (n = 25) and Berne's modification (n = 29). Two studies comparing the Beger and Frey procedure were entered into a meta-analysis and showed no difference in post operative pain (RD = -0.06; CI -0.21 to 0.09), mortality (RD = 0.01; CI -0.03 to 0.05), morbidity (RD = 0.12; CI -0.00 to 0.24), exocrine insufficiency (RD = 0.04; CI -0.10 to 0.18) and endocrine insufficiency (RD = -0.14 CI -0.28 to 0.01). CONCLUSION: All procedures are equally effective for the management of pain for chronic pancreatitis. The choice of procedure should be determined by other factors including the presence of secondary complications of pancreatitis and intra-operative findings. Registration number CRD42015019275. Centre for Reviews and Dissemination, University of York, 2009. PMID- 26902129 TI - Robot-assisted laparoscopic liver resection: a systematic review and pooled analysis of minor and major hepatectomies. AB - BACKGROUND: Robotic surgery has been introduced to overcome the limitations of conventional laparoscopy. A systematic review and meta-analysis were performed to assess the safety and feasibility for three subgroups of robot-assisted laparoscopic liver resection: (i) minor resections of easily accessible segments: 2/3, 4B, 5, 6, (ii) minor resections of difficult located segments: 1, 4A, 7, 8 and (iii) major resections: >= 4 segments. METHODS: A systematic search was performed in PubMed, EMBASE and Cochrane Library. RESULTS: Twelve observational, mostly retrospective studies reporting on 363 patients were included. Data were pooled and analyzed. For subgroup (i) (n = 81) the weighted mean operative time was 215 +/- 65 min. One conversion (1%) to laparotomy was needed. Weighted mean operative time for subgroup (ii) (n = 17) was 220 +/- 60 min. No conversions were needed. For subgroup (iii) (n = 99) the weighted mean operative time was 405 +/- 100 min. In this subgroup 8 robotic procedures (8%) were converted to open surgery. CONCLUSION: Data show that robot-assisted laparoscopic liver resection is feasible in minor resections of all segments and major resections. Larger, prospective studies are warranted to compare the possible advantages of robot assisted surgery with conventional laparoscopy and open surgery. PMID- 26902131 TI - A literature review of radiological findings to guide the diagnosis of gallbladder adenomyomatosis. AB - BACKGROUND: Gallbladder adenomyomatosis (GA) is a benign gallbladder entity discovered as an asymptomatic gallbladder mass. Since gallbladder cancer is in the differential diagnosis for gallbladder masses, the ability to differentiate benign disease avoids a more extensive oncologic resection. This study sought to review imaging modalities used to diagnose GA. METHODS: PubMed and SciVerse Scopus were systematically searched using the terms: "gallbladder adenomyomatosis" and "gallbladder imaging" for articles published between January 2000 and January 2015. RESULTS: A total of 14 articles were reviewed in this analysis. Contemporary series report the use of ultrasound (US), computed tomography (CT) or magnetic resonance imaging (MRI) in GA imaging. Ultrasound detection of Rokitansky-Aschoff sinuses, visualized as small cystic spaces with associated "comet-tail" or "twinkling" artifact, is pathognomonic for GA. A "Pearl-Necklace" sign of small connected sinuses on MRI or "Rosary" sign on CT are additional characteristics that may assist in establishing a diagnosis. CONCLUSION: Ultrasound is the most commonly used tool to investigate GA. If not diagnostic, CT or MRI are effective in attempting to differentiate a benign or malignant cholecystic mass. Characteristic signs should lead the surgeon to perform a laparoscopic cholecystectomy in symptomatic patients or manage non operatively in asymptomatic patients. PMID- 26902132 TI - Intraoperative monitoring of stroke volume variation versus central venous pressure in laparoscopic liver surgery: a randomized prospective comparative trial. AB - BACKGROUND: Central venous pressure (CVP) is used as a marker of cardiac preload to control intraoperative blood loss in open hepatectomies, while its reliability in laparoscopy is less certain. The aim of this randomized prospective trial was to evaluate the outcome of laparoscopic resections performed with stroke volume variation (SVV) or CVP monitoring. METHODS: All candidates for laparoscopic liver resection were assigned randomly to SVV or to CVP groups. Outcome was evaluated included conversion rate, cause of conversion, intraoperative blood loss, need for transfusions, length of surgery and postoperative results. RESULTS: Ninety consecutive patients were enrolled: both SVV and CVP groups included 45 patients each and were comparable in terms of patient and disease characteristics. A reduced rate of conversion was recorded in the SVV compared to the CVP group (6.7% and 17.8% respectively, p = 0.02). Blood loss was lower in the SVV group (150 mL), compared to the CVP group (300 mL, p = 0.04). Morbidity, mortality, length of stay and functional recovery were comparable. On multivariate analysis, lesion location, extent of hepatectomy and type of cardiac preload monitoring were associated significantly to risk of conversion. CONCLUSION: SVV monitoring in laparoscopic liver surgery improves intraoperative outcome, thus enhancing the benefits of the minimally-invasive approach and fast-track protocols. PMID- 26902133 TI - Roux-en-Y pancreaticojejunostomy reconstruction after deep enucleation of benign or borderline pancreatic lesions: a single-institution experience. AB - BACKGROUND: Standard pancreatectomy for benign and borderline pancreatic lesions involves resecting a substantial amount of normal pancreatic parenchyma and leads to a subsequent impairment of both exocrine and endocrine pancreatic functions. A limited resection such as enucleation is the preferred option for such neoplasms. However, enucleation is associated with a high risk of postoperative complications in some cases. This study evaluated the feasibility and outcomes of performing deep enucleation with Roux-en-Y pancreaticojejunostomy reconstruction. METHODS: This study included patients who underwent pancreatic lesion enucleation from February 2010 to April 2014 in our hospital. The clinical data were collected and retrospectively analyzed. RESULTS: This study examined 53 patients who underwent enucleation, 33 of the procedures included deep enucleation with Roux-en-Y pancreaticojejunostomy reconstruction. There was no mortality, and the morbidity rate was 66.7% in this group. No patients developed grade C pancreatic fistulas in both group. None of the patients developed tumor recurrence or exocrine or endocrine insufficiency at a median follow-up of 25 months. DISCUSSION: Enucleation with Roux-en-Y pancreaticojejunostomy reconstruction is a safe and feasible procedure for the treatment of benign and borderline pancreatic neoplasms adjacent to the common pancreatic duct. This procedure can effectively mitigate the limitations of simple enucleation. PMID- 26902134 TI - Evaluation of an enhanced recovery protocol after pancreaticoduodenectomy in elderly patients. AB - BACKGROUND: Recent evidence has shown that enhanced recovery after surgery (ERAS) protocols decrease hospital stay following pancreaticoduodenectomy (PD). The aims of this study were to assess the feasibility and to evaluate the effect of introducing ERAS principles after PD in elderly patients. METHODS: Patients >=75 years were defined as elderly. Comparison of postoperative outcome was performed between 22 elderly patients who underwent ERAS (elderly ERAS + patients) and a historical cohort of 66 elderly patients who underwent standard protocols (elderly ERAS-patients). RESULTS: The lowest adherence with ERAS among elderly patients was observed for starting a solid food diet within POD 4 (n = 7) and early drains removal (n = 2). The highest adherence was observed for post operative glycemic control (n = 21), epidural analgesia (n = 21), mobilization (n = 20) and naso-gastric removal in POD 0 (n = 20). Post-operative outcomes did not differ between elderly ERAS+ and elderly ERAS- patients. In patients with an uneventful postoperative course, the median intention to discharge was earlier in elderly ERAS + patients as compared to the elderly ERAS- patients (4 days versus 8 days, P < 0.001). CONCLUSION: An ERAS protocol following PD seems to be feasible and safe among elderly although it is not associated with improved postoperative outcomes. PMID- 26902135 TI - Lung ultrasonography as a direct measure of evolving respiratory dysfunction and disease severity in patients with acute pancreatitis. AB - BACKGROUND: The value of lung ultrasonography in the diagnosis of respiratory dysfunction and severity stratification in patients with acute pancreatitis (AP) was investigated. METHODS: Over a 3-month period, 41 patients (median age: 59.1 years; 21 males) presenting with a diagnosis of potential AP were prospectively recruited. Each participant underwent lung ultrasonography and the number of comet tails was linked with contemporaneous clinical data. Group comparisons, areas under the curve (AUC) and respective measures of diagnostic accuracy were investigated. RESULTS: A greater number of comet tails were evident in patients with respiratory dysfunction (P = 0.021), those with severe disease (P < 0.001) and when contemporaneous and maximum CRP exceeded 100 mg/L (P = 0.048 and P = 0.003 respectively). Receiver-operator characteristic plot area under the curve (AUC) was greater when examining upper lung quadrants, using respiratory dysfunction and AP severity as variables of interest (AUC = 0.783, 95% C.I.: 0.544-0.962, and AUC = 0.996, 95% C.I.: 0.982-1.000, respectively). Examining all lung quadrants except for the lower lateral resulted in greater AUCs for contemporaneous and maximum CRP (AUC = 0.708, 95% C.I.: 0.510-0.883, and AUC = 0.800, 95% C.I.: 0.640-0.929). DISCUSSION: Ultrasonography of non-dependent lung parenchyma can reliably detect evolving respiratory dysfunction in AP. This simple bedside technique shows promise as an adjunct to severity stratification. PMID- 26902136 TI - Pan-European survey on the implementation of minimally invasive pancreatic surgery with emphasis on cancer. AB - BACKGROUND: Minimally invasive (MI) pancreatic surgery appears to be gaining popularity, but its implementation throughout Europe and the opinions regarding its use in pancreatic cancer patients are unknown. METHODS: A 30-question survey was sent between June and December 2014 to pancreatic surgeons of the European Pancreatic Club, European-African Hepato-Pancreato-Biliary Association and 5 European national pancreatic societies. Incomplete responses were excluded. RESULTS: In total, 237 pancreatic surgeons responded. After excluding 34 incomplete responses, 203 responses from 27 European countries were included. 164 (81%) surgeons were employed at a university hospital, 184 (91%) performed advanced MI surgery and 148 (73%) performed MI distal pancreatectomy. MI pancreatoduodenectomy was performed by 42 (21%) surgeons, whereas 9 (4.4%) surgeons had performed more than 10 procedures. Robot-assisted MI pancreatic surgery was performed by 28 (14%) surgeons. 63 (31%) surgeons expected MI distal pancreatectomy for cancer to be inferior to open distal pancreatectomy concerning oncological outcomes. 151 (74%) surgeons expected to benefit from training in MI distal pancreatectomy and 149 (73%) were willing to participate in a randomized trial on this topic. CONCLUSIONS: MI distal pancreatectomy is a common procedure, although its use for cancer is still disputed. MI pancreatoduodenectomy is still an uncommon procedure. Specific training and a randomized trial regarding MI pancreatic cancer surgery are welcomed. PMID- 26902137 TI - Short-term outcomes after liver resection for malignant and benign disease in the age of ERAS. AB - INTRODUCTION: Enhanced Recovery After Surgery protocols have been implemented effectively after liver resection and provide benefits in terms of general morbidity rates. In order to optimise peri-operative care protocols and minimise morbidity, further investigation is required to identify factors associated with poor outcome after liver resection. METHODS: A retrospective analysis of patients undergoing liver resection and enhanced recovery care between January 2006 and September 2012 was conducted. Data were collected on patient outcome and demographics, operative and pathological details. Univariate and multivariate analyses were performed to determine independent predictors of adverse outcome. RESULTS: 603 patients underwent liver resection during the study period. Morbidity and mortality rates were 34.3% and 1.5% respectively. The only predictor of major morbidity was extended resection (OR 4.079; 95% CI 2.177 7.642). CONCLUSIONS: Extended resection is associated with major morbidity. When determining optimum peri-operative care, ERAS protocols must incorporate care components that can mitigate against morbidity associated with extended resection. PMID- 26902138 TI - Long-term survival in laparoscopic vs open resection for colorectal liver metastases: inverse probability of treatment weighting using propensity scores. AB - BACKGROUND: This study compares long-term outcomes between intention-to-treat laparoscopic and open approaches to colorectal liver metastases (CLM), using inverse probability of treatment weighting (IPTW) based on propensity scores to control for selection bias. METHOD: Patients undergoing liver resection for CLM by 5 surgeons at 3 institutions from 2000 to early 2014 were analysed. IPTW based on propensity scores were generated and used to assess the marginal treatment effect of the laparoscopic approach via a weighted Cox proportional hazards model. RESULTS: A total of 298 operations were performed in 256 patients. 7 patients with planned two-stage resections were excluded leaving 284 operations in 249 patients for analysis. After IPTW, the population was well balanced. With a median follow up of 36 months, 5-year overall survival (OS) and recurrence-free survival (RFS) for the cohort were 59% and 38%. 146 laparoscopic procedures were performed in 140 patients, with weighted 5-year OS and RFS of 54% and 36% respectively. In the open group, 138 procedures were performed in 122 patients, with a weighted 5-year OS and RFS of 63% and 38% respectively. There was no significant difference between the two groups in terms of OS or RFS. CONCLUSION: In the Brisbane experience, after accounting for bias in treatment assignment, long term survival after LLR for CLM is equivalent to outcomes in open surgery. PMID- 26902139 TI - The relationship of blood transfusion with peri-operative and long-term outcomes after major hepatectomy for metastatic colorectal cancer: a multi-institutional study of 456 patients. AB - BACKGROUND: Data on prognostic implications of peri-operative blood transfusion around resection of colorectal cancer liver metastases (CRLM) are conflicting. This retrospective study assesses the association of transfusion with complications and disease-specific survival (DSS). METHODS: Major hepatectomies for CRLM from 2000 to 2010 at three institutions were included. Transfusion was analyzed based on timing and volume. RESULTS: Of 456 patients, 140 (30.7%) received transfusions. Transfusion was associated with extended hepatectomy (28.6 vs 18.4%; p = 0.020), tumor size (5.7 vs 4.2 cm; p < 0.001), and operative blood loss (917 vs 390 mL; p < 0.001). Transfusion was independently associated with major complications (OR 2.61; 95% CI: 1.53-4.44; p < 0.001). Transfusion at any time was not associated with DSS; however, patients who specifically received blood post-operatively had reduced DSS (37.4 vs 42.7 months; p = 0.044). Increased volume of transfusion (>=3 units) was also associated with shortened DSS (Total: 37.4 vs 41.5 months, p = 0.018; Post-operative: 27.2 vs 40.3 months, p = 0.015). On multivariate analysis, however, transfusion was not independently associated with worsened DSS, regardless of timing and volume. CONCLUSION: Transfusion with major hepatectomy for colorectal cancer metastases is independently associated with increased complications but not disease-specific survival. Judicious use of transfusion per a blood utilization protocol in the peri-operative period is warranted. PMID- 26902140 TI - Serial volumetric assessment of large for size liver grafts after whole cadaveric liver transplant in adults: do large liver grafts shrink in size? AB - BACKGROUND: After whole graft orthotopic liver transplantation (OLT), adaptation of the large grafts' volume to recipient weight is widely accepted despite the paucity of evidence on this subject. METHODS: Thirty nine patients with GRWR > 2.5% were included in this study and subsequently divided into two groups with 3 >= GRWR > 3%. Patients had CT scans at three predetermined time points after OLT used for measuring the liver volume. The objective of this study is to evaluate the volumetric changes of whole large liver grafts after adult OLT. RESULTS: At LT, the mean graft recipient body weight ratio (GRWR) was 3.1 +/- 0.4%. The mean liver weight was 1881 +/- 68 g at LT, 2014 +/- 99 ml at one week, 1725 +/- 126 ml at 3 months, and 1632 +/- 117 (ml) at >6 months. There is an initial increase at 1 week after LT and a subsequent decrease of liver volume on later measurements. None of the late volume measurements were significantly different from the initial graft volume at liver transplant in pair wise comparisons ANOVA repeated measures (p > 0.05). Similarly, the mean GRWR did not change significantly between the initial calculation at transplantation date and the subsequent measurements during the different study time points (F = 0.04, p = 0.96) with a mean of 3.1% (95% CI = 2.2-4.2). AUC ROC discriminated a cutoff of 3% for the initial GRWR above which grafts tend to decrease in size over time (c statistics = 0.74, p = 0.036). In a Clustered ANOVA repeated measures, there was no significant difference in the changes of liver volume between both groups. However, patients with GRWR > 3 showed a trend towards a latent reduction in volume over the tracing period. There was a tendency, but none significant; towards a higher bilirubin, AST, ALT levels over the first postoperative days in recipients with GRWR > 3. CONCLUSION: Large grafts do not significantly decrease in size. Nonetheless, grafts weighing >3% of the GRWR show a different trend towards decrease in size over time. PMID- 26902141 TI - Video-assisted hepatic abscess debridement. PMID- 26902143 TI - Retinoschisis in Pars Planitis. AB - PURPOSE: To describe the course of retinoschisis in patients with pars planitis (PP). METHODS: Chart review of PP patients seen July 2012-September 2014 at a single institution. RESULTS: Included were 34 patients (68 eyes). Uveitis was bilateral in all cases. Thirteen eyes (19%) developed retinoschisis. In six patients (86%), the schisis was bilateral. The average follow-up of patients with schisis was 7 years; the average best-corrected visual acuity (BCVA) was 20/22 at last follow-up. Schisis was noted to develop or progress in patients with both active and inactive inflammation. Five eyes of five patients underwent vitrectomy; three for disease control, with scleral buckle to reduce residual traction. Two eyes required vitrectomy for retinal detachment with progressive schisis, despite inactive uveitis. Seven eyes remained stable without intervention. CONCLUSIONS: Retinoschisis is a common complication in patients with PP. It is typically bilateral, and may develop or progress, despite control of uveitis. PMID- 26902146 TI - Implantable Defibrillator Timing Windows: When Coincidence Can Be Confusing. PMID- 26902145 TI - BRCA1 inhibits AR-mediated proliferation of breast cancer cells through the activation of SIRT1. AB - Breast cancer susceptibility gene 1 (BRCA1) is a tumor suppressor protein that functions to maintain genomic stability through critical roles in DNA repair, cell-cycle arrest, and transcriptional control. The androgen receptor (AR) is expressed in more than 70% of breast cancers and has been implicated in breast cancer pathogenesis. However, little is known about the role of BRCA1 in AR mediated cell proliferation in human breast cancer. Here, we report that a high expression of AR in breast cancer patients was associated with shorter overall survival (OS) using a tissue microarray with 149 non-metastatic breast cancer patient samples. We reveal that overexpression of BRCA1 significantly inhibited expression of AR through activation of SIRT1 in breast cancer cells. Meanwhile, SIRT1 induction or treatment with a SIRT1 agonist, resveratrol, inhibits AR stimulated proliferation. Importantly, this mechanism is manifested in breast cancer patient samples and TCGA database, which showed that low SIRT1 gene expression in tumor tissues compared with normal adjacent tissues predicts poor prognosis in patients with breast cancer. Taken together, our findings suggest that BRCA1 attenuates AR-stimulated proliferation of breast cancer cells via SIRT1 mediated pathway. PMID- 26902147 TI - Inappropriately Appropriate. PMID- 26902149 TI - Self-assembled ion-pair organocatalysis--asymmetric Baeyer-Villiger oxidation mediated by flavinium-cinchona alkaloid dimer. AB - An ion-pair catalyst generated by assembly of a chiral flavinium and a cinchona alkaloid dimer for use in asymmetric Baeyer-Villiger oxidation is presented. Ion pair formation is essential for enhancing the catalytic activity and stereoselectivity. The catalyst is applicable to structurally diverse 3 substituted cyclobutanones, providing good to excellent enantioselectivities (up to 98 : 2 e.r.). This study provides the first example of self-assembly of a flavin derivative and a base to form a chiral reaction site that enables a highly stereoselective reaction to occur. PMID- 26902150 TI - Site-specific metal and ligand substitutions in a microporous Mn(2+)-based metal organic framework. AB - The precise tuning of the structural and chemical features of microporous metal organic frameworks (MOFs) is a crucial endeavour for developing materials with properties that are suitable for specific applications. In recent times, techniques for preparing frameworks consisting of mixed-metal or ligand compositions have emerged. However, controlled spatial organisation of the components within these structures at the molecular scale is a difficult challenge, particularly when species possessing similar geometries or chemical properties are used. Here, we describe the synthesis of mixed-metal and ligand variants possessing the Mn3L3 (Mn-MOF-1; H2L = bis(4-(4'-carboxyphenyl)-3,5 dimethylpyrazolyl)methane) structure type. In the case of mixed-ligand synthesis using a mixture of L and its trifluoromethyl-functionalised derivative (H2L' = bis(4-(4'-carboxyphenyl)-3,5-di(trifluoromethyl)pyrazolyl)methane), a mixed ligand product in which the L' species predominanantly occupies the pillar sites lining the pores is obtained. Meanwhile, post-synthetic metal exchange of the parent Mn3L3 compound using Fe(2+) or Fe(3+) ions results in a degree of cation exchange at the trinuclear carboxylate-based clusters and metalation at the pillar bispyrazolate sites. The results demonstrate the versatility of the Mn3L3 structure type toward both metal and ligand substitutions, and the potential utility of site-specific functionalisations in achieving even greater precision in the tuning of MOFs. PMID- 26902148 TI - Jasmonic acid is a crucial signal transducer in heat shock induced sesquiterpene formation in Aquilaria sinensis. AB - Agarwood, a highly valuable resinous and fragrant heartwood of Aquilaria plants, is widely used in traditional medicines, incense and perfume. Only when Aquilaria trees are wounded by external stimuli do they form agarwood sesquiterpene defensive compounds. Therefore, understanding the signaling pathway of wound induced agarwood formation is important. Jasmonic acid (JA) is a well characterized molecule that mediates a plant's defense response and secondary metabolism. However, little is known about the function of endogenous JA in agarwood sesquiterpene biosynthesis. Here, we report that heat shock can up regulate the expression of genes in JA signaling pathway, induce JA production and the accumulation of agarwood sesquiterpene in A. sinensis cell suspension cultures. A specific inhibitor of JA, nordihydroguaiaretic acid (NDGA), could block the JA signaling pathway and reduce the accumulation of sesquiterpene compounds. Additionally, compared to SA and H2O2, exogenously supplied methyl jasmonate has the strongest stimulation effect on the production of sesquiterpene compounds. These results clearly demonstrate the central induction role of JA in heat-shock-induced sesquiterpene production in A. sinensis. PMID- 26902151 TI - Therapeutic Potential of Neuregulin in Cardiovascular System: Can we Ignore the Effects of Neuregulin on Electrophysiology? AB - Neuregulin-1(NRG-1) has now been accepted to have therapeutic potential in cardiovascular disease. The preclinical and clinical researches of NRG-1 have demonstrated its advantage effects in cardiac function with multi-target cardiovascular biology and pathophysiology, but its influence on cardiac electrophysiology is rarely involved, which is a very important aspect and should not be ignored. PMID- 26902154 TI - Generation and Synthetic Application of Trifluoromethyl Diazomethane Utilizing Continuous Flow Technologies. AB - A continuous process for the synthesis and inline separation of anhydrous trifluoromethyl diazomethane in a single continuous flow process is presented. The diazo building block is generated from the corresponding amine and NaNO2 under acidic, aqueous conditions and subsequently diffuses through a gas permeable membrane into an organic stream. To avoid storage and transportation of the hazardous compound, a representative downstream process in a packed-bed reactor yielding highly functionalized building blocks was developed. PMID- 26902152 TI - Regulation of Transcription Factor Yin Yang 1 by SET7/9-mediated Lysine Methylation. AB - Yin Yang 1 (YY1) is a multifunctional transcription factor shown to be critical in a variety of biological processes. Although it is regulated by multiple types of post-translational modifications (PTMs), whether YY1 is methylated, which enzyme methylates YY1, and hence the functional significance of YY1 methylation remains completely unknown. Here we reported the first methyltransferase, SET7/9 (KMT7), capable of methylating YY1 at two highly conserved lysine (K) residues, K173 and K411, located in two distinct domains, one in the central glycine-rich region and the other in the very carboxyl-terminus. Functional studies revealed that SET7/9-mediated YY1 methylation regulated YY1 DNA-binding activity both in vitro and at specific genomic loci in cultured cells. Consistently, SET7/9 mediated YY1 methylation was shown to involve in YY1-regulated gene transcription and cell proliferation. Our findings revealed a novel regulatory strategy, methylation by lysine methyltransferase, imposed on YY1 protein, and linked YY1 methylation with its biological functions. PMID- 26902155 TI - [When gliomes go hand in hand with exosomes]. PMID- 26902156 TI - High-throughput screening of metal-porphyrin-like graphenes for selective capture of carbon dioxide. AB - Nanostructured materials, such as zeolites and metal-organic frameworks, have been considered to capture CO2. However, their application has been limited largely because they exhibit poor selectivity for flue gases and low capture capacity under low pressures. We perform a high-throughput screening for selective CO2 capture from flue gases by using first principles thermodynamics. We find that elements with empty d orbitals selectively attract CO2 from gaseous mixtures under low CO2 pressures (~10(-3) bar) at 300 K and release it at ~450 K. CO2 binding to elements involves hybridization of the metal d orbitals with the CO2 pi orbitals and CO2-transition metal complexes were observed in experiments. This result allows us to perform high-throughput screening to discover novel promising CO2 capture materials with empty d orbitals (e.g., Sc- or V-porphyrin like graphene) and predict their capture performance under various conditions. Moreover, these findings provide physical insights into selective CO2 capture and open a new path to explore CO2 capture materials. PMID- 26902157 TI - Resonating with the ghost of a hand: A TMS experiment. AB - An impressive body of literature in the past 20 years has revealed a possible role played by cortical motor areas in action perception. One question that has been of interest is whether these areas are selectively tuned to process the actions of biological agents. However, no experiments directly testing the effects of the main characteristics identifying a biological agent (physical appearance and movement kinematics) on corticospinal excitability (CS) are present in literature. To fill this gap, we delivered single-pulse transcranial magnetic stimulation to the primary motor cortex and we recorded motor evoked potentials from contralateral hand muscles during observation of point-light displays stimuli representing a hand having lost its physical appearance (Experiment 1) and kinematics characteristics (Experiment 2). Results showed that physical appearance, natural kinematics, and the possibility to identify the action behind the stimulus are not necessary conditions to modulate CS excitability during stimuli observation. We propose that the involvement of the motor system can be mandatory whenever the perceived movement, executed by a human, by an animal or by an object, is recognized as reproducible in its final outcome (e.g., position in space, direction of movement, posture of a body part, to-be-produced sound, specific interaction with an object, etc.), and that the peculiar relationship existing between others' actions and the actions executed by the observer could just represent the extreme in which the motor system is able to almost perfectly reproduce the observed stimulus as it unfolds and, consequently, contribute to stimulus perception in the most efficient way. PMID- 26902158 TI - Congruency of body-related information induces somatosensory reorganization. AB - Chronic pain and impaired tactile sensitivity are frequently associated with "blurred" representations in the somatosensory cortex. The factors that produce such somatosensory blurring, however, remain poorly understood. We manipulated visuo-tactile congruence to investigate its role in promoting somatosensory reorganization. To this aim we used the mirror box illusion that produced in participants the subjective feeling of looking directly at their left hand, though they were seeing the reflection of their right hand. Simultaneous touches were applied to the middle or ring finger of each hand. In one session, the same fingers were touched (for example both middle fingers), producing a congruent percept; in the other session different fingers were touched, producing an incongruent percept. In the somatosensory system, suppressive interactions between adjacent stimuli are an index of intracortical inhibitory function. After each congruent and incongruent session, we recorded somatosensory evoked potential (SEPs) elicited by electrocutaneous stimulation of the left ring and middle fingers, either individually or simultaneously. A somatosensory suppression index (SSI) was calculated as the difference in amplitude between the sum of potentials evoked by the two individually stimulated fingers and the potentials evoked by simultaneous stimulation of both fingers. This SSI can be taken as an index of the strength of inhibitory interactions and consequently can provide a measure of how distinct the representations of the two fingers are. Results showed stronger SSI in the P100 component after congruent than incongruent stimulation, suggesting the key role of congruent sensory information about the body in inducing somatosensory reorganization. PMID- 26902159 TI - A high-resolution melting (HRM) assay for the differentiation between Israeli field and Neethling vaccine lumpy skin disease viruses. AB - Lumpy skin disease (LSD) is a constant threat to the Middle East including the State of Israel. During vaccination programs it is essential for veterinary services and farmers to be able to distinguish between animals affected by the cattle-borne virulent viruses and vaccinated animals, subsequently affected by the vaccine strain. This study describes an improved high resolution-melting (HRM) test that exploits a 27 base pair (bp) fragment of the LSDV126 extracellular enveloped virion (EEV) gene that is present in field viruses but is absent from the Neethling vaccine strain. This difference leads to ~0.5 degrees C melting point change in the HRM assay, when testing the quantitative PCR (qPCR) products generated from the virulent field viruses compared to the attenuated vaccine. By exploiting this difference, it could be shown using the newly developed HRM assay that virus isolated from vaccinated cattle that developed disease symptoms behave similarly to vaccine virus control, indicating that the vaccine virus can induce disease symptoms. This assay is not only in full agreement with the previously published PCR gradient and restriction fragment length polymorphism (RFLP) tests but it is faster with, fewer steps, cheaper and dependable. PMID- 26902160 TI - The Australian Longitudinal Study on Women's Health: Using Focus Groups to Inform Recruitment. AB - BACKGROUND: Recruitment and retention of participants to large-scale, longitudinal studies can be a challenge, particularly when trying to target young women. Qualitative inquiries with members of the target population can prove valuable in assisting with the development of effective recruiting techniques. Researchers in the current study made use of focus group methodology to identify how to encourage young women aged 18-23 to participate in a national cohort online survey. OBJECTIVE: Our objectives were to gain insight into how to encourage young women to participate in a large-scale, longitudinal health survey, as well as to evaluate the survey instrument and mode of administration. METHODS: The Australian Longitudinal Study on Women's Health used focus group methodology to learn how to encourage young women to participate in a large scale, longitudinal Web-based health survey and to evaluate the survey instrument and mode of administration. Nineteen groups, involving 75 women aged 18-23 years, were held in remote, regional, and urban areas of New South Wales and Queensland. RESULTS: Focus groups were held in 2 stages, with discussions lasting from 19 minutes to over 1 hour. The focus groups allowed concord to be reached regarding survey promotion using social media, why personal information was needed, strategies to ensure confidentiality, how best to ask sensitive questions, and survey design for ease of completion. Recruitment into the focus groups proved difficult: the groups varied in size between 1 and 8 participants, with the majority conducted with 2 participants. CONCLUSIONS: Intense recruitment efforts and variation in final focus group numbers highlights the "hard to reach" character of young women. However, the benefits of conducting focus group discussions as a preparatory stage to the recruitment of a large cohort for a longitudinal Web-based health survey were upheld. PMID- 26902161 TI - Quantitative Survey and Structural Classification of Hydraulic Fracturing Chemicals Reported in Unconventional Gas Production. AB - Much interest is directed at the chemical structure of hydraulic fracturing (HF) additives in unconventional gas exploitation. To bridge the gap between existing alphabetical disclosures by function/CAS number and emerging scientific contributions on fate and toxicity, we review the structural properties which motivate HF applications, and which determine environmental fate and toxicity. Our quantitative overview relied on voluntary U.S. disclosures evaluated from the FracFocus registry by different sources and on a House of Representatives ("Waxman") list. Out of over 1000 reported substances, classification by chemistry yielded succinct subsets able to illustrate the rationale of their use, and physicochemical properties relevant for environmental fate, toxicity and chemical analysis. While many substances were nontoxic, frequent disclosures also included notorious groundwater contaminants like petroleum hydrocarbons (solvents), precursors of endocrine disruptors like nonylphenols (nonemulsifiers), toxic propargyl alcohol (corrosion inhibitor), tetramethylammonium (clay stabilizer), biocides or strong oxidants. Application of highly oxidizing chemicals, together with occasional disclosures of putative delayed acids and complexing agents (i.e., compounds designed to react in the subsurface) suggests that relevant transformation products may be formed. To adequately investigate such reactions, available information is not sufficient, but instead a full disclosure of HF additives is necessary. PMID- 26902162 TI - Nimbolide, a neem limonoid inhibits Phosphatidyl Inositol-3 Kinase to activate Glycogen Synthase Kinase-3beta in a hamster model of oral oncogenesis. AB - Glycogen synthase kinase-3beta (GSK-3beta), a serine/threonine kinase is frequently inactivated by the oncogenic signalling kinases PI3K/Akt and MAPK/ERK in diverse malignancies. The present study was designed to investigate GSK-3beta signalling circuits in the 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis model and the therapeutic potential of the neem limonoid nimbolide. Inactivation of GSK-3beta by phosphorylation at serine 9 and activation of PI3K/Akt, MAPK/ERK and beta-catenin was associated with increased cell proliferation and apoptosis evasion during stepwise evolution of HBP carcinomas. Administration of nimbolide inhibited PI3K/Akt signalling with consequent activation of GSK-3beta thereby inducing trafficking of beta-catenin away from the nucleus and enhancing the expression of miR-126 and let-7. Molecular docking studies confirmed interaction of nimbolide with PI3K, Akt, ERK and GSK-3beta. Furthermore, nimbolide attenuated cell proliferation and induced apoptosis as evidenced by increased p-cyclin D1(Thr286) and pro-apoptotic proteins. The present study has unravelled aberrant phosphorylation as a key determinant for oncogenic signalling and acquisition of cancer hallmarks in the HBP model. The study has also provided mechanistic insights into the chemotherapeutic potential of nimbolide that may be a useful addition to the armamentarium of natural compounds targeting PI3K for oral cancer treatment. PMID- 26902163 TI - Variation in KRAS driver substitution distributions between tumor types is determined by both mutation and natural selection. AB - Different tumor types vary greatly in their distribution of driver substitutions. Here, we analyzed how mutation and natural selection contribute to differences in the distribution of KRAS driver substitutions between lung, colon and pancreatic adenocarcinomas. We were able to demonstrate that both differences in mutation and differences in selection drive variation in the distribution of KRAS driver substitutions between tumor types. By accounting for the effects of mutation on the distribution of KRAS driver substitutions, we could identify specific KRAS driver substitutions that are more favored by selection in specific tumor types. Such driver substitutions likely improve fitness most when they occur within the context of the tumor type in which they are preferentially favored. Fitting with this, we found that driver substitutions that are more favored by natural selection in a specific type of tumor tend to associate with worse clinical outcomes specifically in that type of tumor. PMID- 26902164 TI - Validity of a Semi-Quantitative Food Frequency Questionnaire for Collegiate Athletes. AB - BACKGROUND: Food frequency questionnaires (FFQs) have been developed and validated for various populations. To our knowledge, however, no FFQ has been validated for young athletes. Here, we investigated whether an FFQ that was developed and validated to estimate dietary intake in middle-aged persons was also valid for estimating that in young athletes. METHODS: We applied an FFQ that had been developed for the Japan Public Health Center-based Prospective Cohort Study with modification to the duration of recollection. A total of 156 participants (92 males) completed the FFQ and a 3-day non-consecutive 24-hour dietary recall (24hDR). Validity of the mean estimates was evaluated by calculating the percentage differences between the 24hDR and FFQ. Ranking estimation was validated using Spearman's correlation coefficient (CC), and the degree of miscategorization was determined by joint classification. RESULTS: The FFQ underestimated energy intake by approximately 10% for both males and females. For 35 nutrients, the median (range) deattenuated CC was 0.30 (0.10 to 0.57) for males and 0.32 (-0.08 to 0.62) for females. For 19 food groups, the median (range) deattenuated CC was 0.32 (0.17 to 0.72) for males and 0.34 (-0.11 to 0.58) for females. For both nutrient and food group intakes, cross-classification analysis indicated extreme miscategorization rates of 3% to 5%. CONCLUSIONS: An FFQ developed and validated for middle-aged persons had comparable validity among young athletes. This FFQ might be useful for assessing habitual dietary intake in collegiate athletes, especially for calcium, vitamin C, vegetables, fruits, and milk and dairy products. PMID- 26902165 TI - Can You Ride a Bicycle? The Ability to Ride a Bicycle Prevents Reduced Social Function in Older Adults With Mobility Limitation. AB - BACKGROUND: The health benefits of bicycling in older adults with mobility limitation (ML) are unclear. We investigated ML and functional capacity of older cyclists by evaluating their instrumental activities of daily living (IADL), intellectual activity, and social function. METHODS: On the basis of interviews, 614 community-dwelling older adults (after excluding 63 participants who never cycled) were classified as cyclists with ML, cyclists without ML, non-cyclists with ML (who ceased bicycling due to physical difficulties), or non-cyclists without ML (who ceased bicycling for other reasons). A cyclist was defined as a person who cycled at least a few times per month, and ML was defined as difficulty walking 1 km or climbing stairs without using a handrail. Functional capacity and physical ability were evaluated by standardized tests. RESULTS: Regular cycling was documented in 399 participants, and 74 of them (18.5%) had ML; among non-cyclists, 49 had ML, and 166 did not. Logistic regression analysis for evaluating the relationship between bicycling and functional capacity revealed that non-cyclists with ML were more likely to have reduced IADL and social function compared to cyclists with ML. However, logistic regression analysis also revealed that the risk of bicycle-related falls was significantly associated with ML among older cyclists. CONCLUSIONS: The ability and opportunity to bicycle may prevent reduced IADL and social function in older adults with ML, although older adults with ML have a higher risk of falls during bicycling. It is important to develop a safe environment for bicycling for older adults. PMID- 26902166 TI - Association Between Maternal Smoking During Pregnancy and Birth Weight: An Appropriately Adjusted Model From the Japan Environment and Children's Study. AB - BACKGROUND: There has been no large nationwide population-based study to examine the effects of maternal smoking status during pregnancy on birth weight that simultaneously controlled for clinical information, socioeconomic status, and maternal weight. Thus, this study aimed to determine the association between maternal smoking status during pregnancy and birth weight, while taking these confounding factors into consideration. METHODS: This study examined the first year fixed dataset from a large nationwide birth cohort study that commenced in 2011. The dataset consisted of information on 9369 singleton infants born before December 31, 2011. Children were divided into 4 groups for statistical analysis: those born to mothers who did not smoke (NS), who quit smoking before pregnancy, who quit smoking during early pregnancy, and who smoked (SM). Multiple linear regression models were conducted for each sex to examine the association between maternal smoking status during early pregnancy and fetal growth. Birth weight was estimated using the least-squares method after controlling for covariates. RESULTS: After controlling for potential confounding factors, maternal smoking status during pregnancy was significantly associated with birth weight. There was a significant difference in birth weight between NS and SM for both male and female infants (male infants, 3096.2 g [NS] vs 2959.8 g [SM], P < 0.001; female infants, 3018.2 g [NS] vs 2893.7 g [SM], P < 0.001). CONCLUSIONS: Using data from a large nationwide birth cohort study in Japan, we have shown that maternal smoking during pregnancy may reduce birth weight by 125-136 g. PMID- 26902167 TI - The Effect of Continuity of Care on Emergency Room Use for Diabetic Patients Varies by Disease Severity. AB - BACKGROUND: Although many studies have reported that high-quality continuity of care (COC) is associated with improved patient outcomes for patients with diabetes, few studies have investigated whether this positive effect of COC depends on the level of diabetes severity. METHODS: A total of 3781 newly diagnosed diabetic patients selected from the 2005 National Health Insurance database were evaluated for the period 2005-2011. Generalized estimating equations combined with negative binomial estimation were used to determine the influence of COC on the overall emergency room (ER) use and diabetes mellitus (DM)-specific ER use. Analyses were stratified according to diabetes severity (measured using the Diabetes Complications Severity Index [DCSI]), comorbidities (measured using the Charlson comorbidity score), and age. RESULTS: COC effects varied according to diabetes severity. Stratified analysis showed that the positive effect of COC on DM-specific ER use was the highest for a DCSI of 0 (least severe), with an incidence rate ratio (IRR) of 0.49 (95% CI, 0.41-0.59) in the high-COC group (reference group: low-COC group). Compared with the low-COC group, high-quality COC had a significant beneficial effect on overall ER use in younger patients (IRR 0.51; 95% CI, 0.39-0.66 for the youngest [18-40 years] group, and IRR 0.67; 95% CI, 0.59-0.76 for the oldest [>65 years] group) and those with a high number of comorbidities. CONCLUSIONS: The positive effects of high-quality COC on the treatment outcomes of patient with diabetes, based on the overall and DM-specific ER use, depends on the level of disease severity. Therefore, providing health education to enhance high-quality COC when the disease severity is low may be critical for ensuring optimal positive effects during diabetes disease progression. PMID- 26902168 TI - Investigation of Spatial Clustering of Biliary Tract Cancer Incidence in Osaka, Japan: Neighborhood Effect of a Printing Factory. AB - BACKGROUND: In 2013, an unusually high incidence of biliary tract cancer among current or former workers of the offset color proof printing department of a printing company in Osaka, Japan, was reported. The purpose of this study was to examine whether distance from the printing factory was associated with incidence of biliary tract cancer and whether incident biliary tract cancer cases clustered around the printing factory in Osaka using population-based cancer registry data. METHODS: We estimated the age-standardized incidence ratio of biliary tract cancer according to distance from this printing factory. We also searched for clusters of biliary tract cancer incidence using spatial scan statistics. RESULTS: We did not observe statistically significantly high or low standardized incidence ratios for residents in each area categorized by distance from the printing factory for the entire sample or for either sex. The scan statistics did not show any statistically significant clustering of biliary tract cancer incidence anywhere in Osaka prefecture in 2004-2007. CONCLUSIONS: There was no statistically significant clustering of biliary tract cancer incidence around the printing factory or in any other areas in Osaka, Japan, between 2004 and 2007. To date, even if some substances have diffused outside this source factory, they do not appear to have influenced the incidence of biliary tract cancer in neighboring residents. PMID- 26902169 TI - Relationship Between Alcohol Drinking Pattern and Risk of Proteinuria: The Kansai Healthcare Study. AB - BACKGROUND: Moderate alcohol consumption has been reported to be associated with a decreased risk of cardiometabolic diseases. Whether drinking pattern is associated with the risk of proteinuria is unknown. METHODS: Study subjects were 9154 non-diabetic Japanese men aged 40-55 years, with an estimated glomerular filtration rate >=60 mL/min/1.73 m(2), no proteinuria, and no use of antihypertensive medications at entry. Data on alcohol consumption were obtained by questionnaire. We defined "consecutive proteinuria" as proteinuria detected twice consecutively as 1+ or higher on urine dipstick at annual examinations. RESULTS: During the 81 147 person-years follow-up period, 385 subjects developed consecutive proteinuria. For subjects who reported drinking 4-7 days per week, alcohol consumption of 0.1-23.0 g ethanol/drinking day was significantly associated with a decreased risk of consecutive proteinuria (hazard ratio [HR] 0.54; 95% confidence interval [CI], 0.36-0.80) compared with non-drinkers. However, alcohol consumption of >=69.1 g ethanol/drinking day was significantly associated with an increased risk of consecutive proteinuria (HR 1.78; 95% CI, 1.01-3.14). For subjects who reported drinking 1-3 days per week, alcohol consumption of 0.1-23.0 g ethanol/drinking day was associated with a decreased risk of consecutive proteinuria (HR 0.76; 95% CI, 0.51-1.12), and alcohol consumption of >=69.1 g ethanol/drinking day was associated with an increased risk of consecutive proteinuria (HR 1.58; 95% CI, 0.72-3.46), but these associations did not reach statistical significance. CONCLUSIONS: Men with frequent alcohol consumption of 0.1-23.0 g ethanol/drinking day had the lowest risk of consecutive proteinuria, while those with frequent alcohol consumption of >=69.1 g ethanol/drinking day had an increased risk of consecutive proteinuria. PMID- 26902170 TI - Secondary Data Analysis of National Surveys in Japan Toward Improving Population Health. AB - Secondary data analysis of national health surveys of the general population is a standard methodology for health metrics and evaluation; it is used to monitor trends in population health over time and benchmark the performance of health systems. In Japan, the government has established electronic databases of individual records from national surveys of the population's health. However, the number of publications based on these datasets is small considering the scale and coverage of the surveys. There appear to be two major obstacles to the secondary use of Japanese national health survey data: strict data access control under the Statistics Act and an inadequate interdisciplinary research environment for resolving methodological difficulties encountered when dealing with secondary data. The usefulness of secondary analysis of survey data is evident with examples from the author's previous studies based on vital records and the National Health and Nutrition Surveys, which showed that (i) tobacco smoking and high blood pressure are the major risk factors for adult mortality from non communicable diseases in Japan; (ii) the decrease in mean blood pressure in Japan from the late 1980s to the early 2000s was partly attributable to the increased use of antihypertensive medication and reduced dietary salt intake; and (iii) progress in treatment coverage and control of high blood pressure is slower in Japan than in the United States and Britain. National health surveys in Japan are an invaluable asset, and findings from secondary analyses of these surveys would provide important suggestions for improving health in people around the world. PMID- 26902172 TI - Development and characterization of microemulsions containing hyaluronic acid. AB - Tween80 and Span20 were used as surfactant mixture for developing non-ionic microemulsions (MEs) containing hyaluronic acid 22 kDa (HA). The effect of Tween80:Span20 ratio (T:S ratio) on microemulsion (ME) water intake and stability was studied. Moreover, the effect of HA on the consumed surfactant amount which is for stabilizing the MEs, for reducing water intake was investigated. Two W/O MEs containing HA were optimized. The first ME was composed of 2% HA, 13.8% Tween:80:Span20 (2:3), 4.2% water and 79.9% isopropylpalmitate (IPP). The second was composed of 2% HA, 16% Span20, 9.6% water:dimethyl sulfoxide (W:DMSO) (6:3.6) and 72.4% medium chain triglycerides (MCTG). The droplet sizes of MEs were determined using dynamic light scattering (DLS). The multilayer membrane system (MLMS) was used for testing the release of HA from both MEs and the released amount of HA was quantified using capillary zone electrophoresis (CZE). Furthermore, three phase diagrams and relevant rheological characteristics were generated. The droplet size of the ME without HA decreased and increased with increasing the temperature. Furthermore, the droplet size of the IPP-ME and MCTG ME without HA and of the MCTG-ME with HA decreased with increasing temperature. In contrast to this results, the droplet size of the IPP-ME with HA increased with increased temperature. This ME belongs to the Newtonian fluids. Compared to the first ME, the second ME shows droplet sizes at 25 degrees C of 6.5 nm without and 37 nm with HA. The droplet size in the second ME decreased proportionally with an increase of the temperature with and without HA. The release of HA was faster from the IPP ME compared to the MCTG-ME. The two developed MEs were stable, isotropic and their properties comply with ME properties concerning the droplet size and viscosity. PMID- 26902173 TI - Some remarks on the first law of photochemistry. AB - The first law of photochemistry stating that light has to be adsorbed in order to cause a photochemical reaction is usually attributed to T. Grotthuss and J. W. Draper, but quite similar observations were earlier reported by J. Beccari. Some key issues in the formulation of this law are briefly discussed. PMID- 26902171 TI - Cognitive Decline in a Colombian Kindred With Autosomal Dominant Alzheimer Disease: A Retrospective Cohort Study. AB - IMPORTANCE: Data from an autosomal dominant Alzheimer disease (ADAD) kindred were used to track the longitudinal trajectory of cognitive decline associated with preclinical ADAD and explore factors that may modify the rate of cognitive decline. OBJECTIVES: To evaluate the onset and rate of cognitive decline during preclinical ADAD and the effect of socioeconomic, vascular, and genetic factors on the cognitive decline. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective cohort study from January 1, 1995, through June 31, 2012, of individuals from Antioquia, Colombia, who tested positive for the ADAD-associated PSEN1 E280A mutation. Data analysis was performed from August 20, 2014, through November 30, 2015. A mixed-effects model was used to estimate annual rates of change in cognitive test scores and to mark the onset of cognitive decline. MAIN OUTCOMES AND MEASURES: Memory, language, praxis, and total scores from the Consortium to Establish a Registry for Alzheimer Disease test battery. Chronologic age was used as a time scale in the models. We explore the effects of sex; educational level; socioeconomic status; residence area; occupation type; marital status; history of hypertension, diabetes mellitus, and dyslipidemia; tobacco and alcohol use; and APOE epsilon4 on the rates of cognitive decline. RESULTS: A total of 493 carriers met the inclusion criteria and were analyzed. A total of 256 carriers had 2 or more assessments. At the time of the initial assessment, participants had a mean (SD) age of 33.4 (11.7) years and a mean (SD) educational level of 7.2 (4.2) years. They were predominantly female (270 [54.8%]), married (293 [59.4%]), and of low socioeconomic status (322 [65.3%]). Word list recall scores provided the earliest indicator of preclinical cognitive decline at 32 years of age, 12 and 17 years before the kindred's respective median ages at mild cognitive impairment and dementia onset. After the change point, carriers had a statistically significant cognitive decline with a loss of 0.24 (95% CI, -0.26 to -0.22) points per year for the word list recall test and 2.13 (95% CI, -2.29 to -1.96) points per year for total scores. Carriers with high educational levels had an increase of approximately 36% in the rate of cognitive decline after the change point when compared with those with low educational levels (-2.89 vs -2.13 points per year, respectively). Onset of cognitive decline was delayed by 3 years in individuals with higher educational levels compared with those with lower educational levels. Those with higher educational level, middle/high socioeconomic status, history of diabetes and hypertension, and tobacco and alcohol use had a steeper cognitive decline after onset. CONCLUSIONS AND RELEVANCE: Preclinical cognitive decline was evident in PSEN1 E280A mutation carriers 12 years before the onset of clinical impairment. Educational level may be a protective factor against the onset of cognitive impairment. PMID- 26902174 TI - Endoplasmic reticulum stress regulates inflammation and insulin resistance in skeletal muscle from pregnant women. AB - Sterile inflammation and infection are key mediators of inflammation and peripheral insulin resistance associated with gestational diabetes mellitus (GDM). Studies have shown endoplasmic reticulum (ER) stress to induce inflammation and insulin resistance associated with obesity and type 2 diabetes, however is paucity of studies investigating the effects of ER stress in skeletal muscle on inflammation and insulin resistance associated with GDM. ER stress proteins IRE1alpha, GRP78 and XBP-1s were upregulated in skeletal muscle of obese pregnant women, whereas IRE1alpha was increased in GDM women. Suppression of ER stress, using ER stress inhibitor tauroursodeoxycholic acid (TUDCA) or siRNA knockdown of IRE1alpha and GRP78, significantly downregulated LPS-, poly(I:C)- or IL-1beta-induced production of IL-6, IL-8, IL-1beta and MCP-1. Furthermore, LPS-, poly(I:C)- or TNF-alpha-induced insulin resistance was improved following suppression of ER stress, by increasing insulin-stimulated phosphorylation of IR beta, IRS-1, GLUT-4 expression and glucose uptake. In summary, our inducible obesity and GDM-like models suggests that the development of GDM may be involved in activating ER stress-induced inflammation and insulin resistance in human skeletal muscle. PMID- 26902176 TI - Biobots. PMID- 26902175 TI - Chitinase producing bacteria with direct algicidal activity on marine diatoms. AB - Chitinase producing bacteria can involve extensively in nutrient cycling and energy flow in the aquatic environment through degradation and utilization of chitin. It is well known that diatoms cells are encased by box-like frustules composed of chitin. Thus the chitin containing of diatoms shall be a natural target of chitinase producing bacteria, however, the interaction between these two organismic groups has not been studied thus far. Therefore, in this study, the algicidal mechanism of one chitinase producing bacterium (strain LY03) on Thalassiosira pseudonana was investigated. The algicidal range and algicidal mode of strain LY03 were first studied, and then bacterial viability, chemotactic ability and direct interaction characteristic between bacteria and diatom were also confirmed. Finally, the characteristic of the intracellular algicidal substance was identified and the algicidal mechanism was determined whereby algicidal bacterial cells showed chemotaxis to algal cells, fastened themselves on algal cells with their flagella, and then produced chitinase to degrade algal cell walls, and eventually caused algal lysis and death. It is the first time to investigate the interaction between chitinase producing bacteria and diatoms, and this novel special interaction mode was confirmed in this study, which will be helpful in protection and utilization of diatoms resources. PMID- 26902177 TI - Dose Evaluation of Fractionated Schema and Distance From Tumor to Spinal Cord for Spinal SBRT with Simultaneous Integrated Boost: A Preliminary Study. AB - BACKGROUND This study investigated and quantified the dosimetric impact of the distance from the tumor to the spinal cord and fractionation schemes for patients who received stereotactic body radiation therapy (SBRT) and hypofractionated simultaneous integrated boost (HF-SIB). MATERIAL AND METHODS Six modified planning target volumes (PTVs) for 5 patients with spinal metastases were created by artificial uniform extension in the region of PTV adjacent spinal cord with a specified minimum tumor to cord distance (0-5 mm). The prescription dose (biologic equivalent dose, BED) was 70 Gy in different fractionation schemes (1, 3, 5, and 10 fractions). For PTV V100, Dmin, D98, D95, and D1, spinal cord dose, conformity index (CI), V30 were measured and compared. RESULTS PTV-to-cord distance influenced PTV V100, Dmin, D98, and D95, and fractionation schemes influenced Dmin and D98, with a significant difference. Distances of >=2 mm, >=1 mm, >=1 mm, and >=0 mm from PTV to spinal cord meet dose requirements in 1, 3, 5, and 10 fractionations, respectively. Spinal cord dose, CI, and V30 were not impacted by PTV-to-cord distance and fractionation schemes. CONCLUSIONS Target volume coverage, Dmin, D98, and D95 were directly correlated with distance from the spinal cord for spine SBRT and HF-SIB. Based on our study, >=2 mm, >=1 mm, >=1 mm, and >=0 mm distance from PTV to spinal cord meets dose requirements in 1, 3, 5 and 10 fractionations, respectively. PMID- 26902178 TI - Study on Light Extraction from GaN-based Green Light-Emitting Diodes Using Anodic Aluminum Oxide Pattern and Nanoimprint Lithography. AB - An anodic aluminum oxide (AAO) patterned sapphire substrate, with the lattice constant of 520 +/- 40 nm, pore dimension of 375 +/- 50 nm, and height of 450 +/- 25 nm was firstly used as a nanoimprint lithography (NIL) stamp and imprinted onto the surface of the green light-emitting diode (LED). A significant light extraction efficiency (LEE) was improved by 116% in comparison to that of the planar LED. A uniform broad protrusion in the central area and some sharp lobes were also obtained in the angular resolution photoluminescence (ARPL) for the AAO patterned LED. The mechanism of the enhancement was correlated to the fluctuations of the lattice constant and domain orientation of the AAO-pattern, which enabled the extraction of more guided modes from the LED device. PMID- 26902179 TI - Highly Functional Bioinspired Fe/N/C Oxygen Reduction Reaction Catalysts: Structure-Regulating Oxygen Sorption. AB - Tuna is one of the most rapid and distant swimmers. Its unique gill structure with the porous lamellae promotes fast oxygen exchange that guarantees tuna's high metabolic and athletic demands. Inspired by this specific structure, we designed and fabricated microporous graphene nanoplatelets (GNPs)-based Fe/N/C electrocatalysts for oxygen reduction reaction (ORR). Careful control of GNP structure leads to the increment of microporosity, which influences the O2 adsorption positively and desorption oppositely, resulting in enhanced O2 diffusion, while experiencing reduced ORR kinetics. Working in the cathode of proton-exchange membrane fuel cells, the GNP catalysts require a compromise between adsorption/desorption for effective O2 exchange, and as a result, appropriate microporosity is needed. In this work, the highest power density, 521 mW.cm(-2), at zero back pressure is achieved. PMID- 26902181 TI - Scattering strength of the scatterer inducing variability in graphene on silicon oxide. AB - Large variability of carrier mobility of graphene-based field effect transistors hampers graphene science and technology. We show that the number of the scatterer responsible for the observed variability on graphene devices on silicon oxide can be determined by finding the number of hydrogen that can be chemisorbed on graphene. We use the relationship between the number of the scatterer and the mobility of graphene devices to determine that the variability-inducing scatterer possesses scattering strength 10 times smaller than that of adsorbed potassium atoms and 50 times smaller than that of ion-beam induced vacancies. Our results provide an important, quantitative input towards determining the origin of the variability. PMID- 26902182 TI - Severe Hypertriglyceridemia in Glut1D on Ketogenic Diet. AB - High-fat ketogenic diets are the only treatment available for Glut1 deficiency (Glut1D). Here, we describe an 8-year-old girl with classical Glut1D responsive to a 3:1 ketogenic diet and ethosuximide. After 3 years on the diet a gradual increase of blood lipids was followed by rapid, severe asymptomatic hypertriglyceridemia (1,910 mg/dL). Serum lipid apheresis was required to determine liver, renal, and pancreatic function. A combination of medium chain triglyceride-oil and a reduction of the ketogenic diet to 1:1 ratio normalized triglyceride levels within days but triggered severe myoclonic seizures requiring comedication with sultiam. Severe hypertriglyceridemia in children with Glut1D on ketogenic diets may be underdiagnosed and harmful. In contrast to congenital hypertriglyceridemias, children with Glut1D may be treated effectively by dietary adjustments alone. PMID- 26902183 TI - Visualizing Plant Cells in a Brand New Way. PMID- 26902180 TI - Clinical correlates of working memory deficits in youth with and without ADHD: A controlled study. AB - OBJECTIVE: Both working memory (WM; a brain system that provides temporary storage and manipulation of the information) and attention-deficit/hyperactivity disorder (ADHD) have been associated with educational deficits. Since WM deficits are prevalent in children with ADHD, the main aim of the present study was to examine whether educational deficits are driven by working memory deficits or driven by the effect of ADHD itself. METHOD: Participants were referred youth with (N = 276) and without (N = 241) ADHD ascertained from pediatric and psychiatric sources. Assessment included measures of psychiatric, psychosocial, educational, and cognitive functioning. Education deficits were defined as grade retention or placement in special classes and were assessed using interviews and written rating scales. Working memory was assessed using the Wechsler Intelligence Scale for Children-Revised (WISC-R) Freedom from Distractibility (FFD) factor based on Digit Span, Arithmetic, and Coding. RESULTS: Significantly more youth with ADHD had WM deficits than controls (31.9% vs. 13.7%, p < .05). In ADHD children, WM deficits were significantly (p < .01) associated with an increased risk for grade retention and placement in special classes as well as lower scores on reading and math achievement tests than for ADHD children without WM deficits. In contrast, no other differences were noted in other areas of functioning. Although WM deficits also had some adverse impact on educational and cognitive correlates in non-ADHD controls, these differences failed to attain statistical significance. CONCLUSION: WM deficits significantly and selectively increase the risk for academic deficits and cognitive dysfunction in children with ADHD beyond those conferred by ADHD. Screening for WM deficits may help identify children with ADHD at high risk for academic and cognitive dysfunction. PMID- 26902184 TI - AtBRO1 Functions in ESCRT-I Complex to Regulate Multivesicular Body Protein Sorting. PMID- 26902185 TI - Current Injection Provokes Rapid Expansion of the Guard Cell Cytosolic Volume and Triggers Ca(2+) Signals. AB - High-resolution microscopy opens the door for detailed single-cell studies with fluorescent reporter dyes and proteins. We used a confocal spinning disc microscope to monitor fluorescent dyes and the fluorescent protein Venus in tobacco and Arabidopsis guard cells. Multi-barreled microelectrodes were used to inject dyes and apply voltage pulses, which provoke transient rises in the cytosolic Ca(2+) level. Voltage pulses also caused changes in the distribution of Lucifer Yellow and Venus, which pointed to a reversible increase of guard cell cytosolic volume. The dynamic cytosolic volume changes turned out to be provoked by current injection of ions. A reduction of the clamp current, by blocking K(+) uptake channels with Cs(+), strongly suppressed the cytosolic volume changes. Cs(+) not only inhibited the expansion of the cytosol, but also inhibited hyperpolarization-induced elevations of the cytosolic Ca(2+) concentration. A complete loss of voltage-induced Ca(2+) signals occurred when Ca(2+)-permeable plasma membrane channels were simultaneously blocked with La(3+). This shows that two mechanisms cause hyperpolarization-induced elevation of the cytosolic Ca(2+) concentration: (i) activation of voltage-dependent Ca(2+)-permeable channels, (ii) osmotically induced expansion of the cytosol, which leads to a release of Ca(2+) from intracellular stores. PMID- 26902187 TI - [New Start, New Hope:]. PMID- 26902186 TI - Plant ABC Transporters Enable Many Unique Aspects of a Terrestrial Plant's Lifestyle. AB - Terrestrial plants have two to four times more ATP-binding cassette (ABC) transporter genes than other organisms, including their ancestral microalgae. Recent studies found that plants harboring mutations in these transporters exhibit dramatic phenotypes, many of which are related to developmental processes and functions necessary for life on dry land. These results suggest that ABC transporters multiplied during evolution and assumed novel functions that allowed plants to adapt to terrestrial environmental conditions. Examining the literature on plant ABC transporters from this viewpoint led us to propose that diverse ABC transporters enabled many unique and essential aspects of a terrestrial plant's lifestyle, by transporting various compounds across specific membranes of the plant. PMID- 26902188 TI - [Retinal morphological and functional abnormalities as biomarker for Alzheimer's disease]. PMID- 26902189 TI - [Ecological executive function characteristics and effects of executive function on social adaptive function in school-aged children with epilepsy]. AB - OBJECTIVE: To explore the characteristics of ecological executive function in school-aged children with idiopathic or probably symptomatic epilepsy and examine the effects of executive function on social adaptive function. METHODS: A total of 51 school-aged children with idiopathic or probably symptomatic epilepsy aged 5-12 years at our hospital and 37 normal ones of the same gender, age and educational level were included. The differences in ecological executive function and social adaptive function were compared between the two groups with the Behavior Rating Inventory of Executive Function (BRIEF) and Child Adaptive Behavior Scale, the Pearson's correlation test and multiple stepwise linear regression were used to explore the impact of executive function on social adaptive function. RESULTS: The scores of school-aged children with idiopathic or probably symptomatic epilepsy in global executive composite (GEC), behavioral regulation index (BRI) and metacognition index (MI) of BRIEF ((62+/-12), (58+/ 13) and (63+/-12), respectively) were significantly higher than those of the control group ((47+/-7), (44+/-6) and (48+/-8), respectively))(P<0.01). The scores of school-aged children with idiopathic or probably symptomatic epilepsy in adaptive behavior quotient (ADQ), independence, cognition, self-control ((86+/ 22), (32+/-17), (49+/-14), (41+/-16), respectively) were significantly lower than those of the control group ((120+/-12), (59+/-14), (59+/-7) and (68+/-10), respectively))(P<0.01). Pearson's correlation test showed that the scores of BRIEF, such as GEC, BRI, MI, inhibition, emotional control, monitoring, initiation and working memory had significantly negative correlations with the score of ADQ, independence, self-control ((r=-0.313--0.741, P<0.05)). Also, GEC, inhibition, MI, initiation, working memory, plan, organization and monitoring had significantly negative correlations with the score of cognition ((r=-0.335- 0.437, P<0.05)); Multiple stepwise linear regression analysis showed that BRI, inhibition and working memory were closely related with the social adaptive function of school-aged children with idiopathic or probably symptomatic epilepsy. CONCLUSIONS: School-aged children with idiopathic or probably symptomatic epilepsy may have significantly ecological executive function impairment and social adaptive function reduction. The aspects of BRI, inhibition and working memory in ecological executive function are significantly related with social adaptive function in school-aged children with epilepsy. PMID- 26902190 TI - [Apoptosis and expression of Caspase 3 and Caspase 4 in neurocytes of refractory human temporal lobe epilepsy]. AB - OBJECTIVE: To study apoptosis and expression of Caspase 3 and Caspase 4 in temporal lobe neurocytes of refractory human temporal lobe epilepsy (TLE). METHODS: The temporal tissue samples were obtained from 30 cases of refractory TLE (TLE group) and 10 cases of brain trauma (contrast group) between January 1993 and May 2008. The surgical specimens were paraffin-embedded samples from Department of Pathology of Fujian Medical University and Department of Neurosurgery, the First Affiliated Hospital of Fujian Medical University. S-P staining of immunohistochemistry was used to detect the expression of Caspase 3 and Caspase 4 in temporal lobe neurocytes of TLE group and contrast group. Their expression was then analyzed. The terminal deoxynucleoitidyl transferase-mediated dUTP nick end labeling (TUNEL) staining was performed to visualize and analyze the neurocytes' apoptosis of two groups. RESULTS: The expression of Caspase 3 and Caspase 4 in neurocytes of TLE group were both higher than that of contrast group (t=12.905, P<0.01; t=11.880, P<0.01). The apoptotic index (AI) of neurocytes in TLE group also increased than that of contrast group (t=9.664, P<0.01). CONCLUSION: Caspase 3 and Caspase 4 may mediate neurocytes apoptosis in temporal lobe tissue of refractory human TLE. PMID- 26902191 TI - [Curative effect analysis of posterior decompression and internal fixation for spinal metastases epidural spinal cord compression]. AB - OBJECTIVE: To explore the effects of posterior decompression and internal fixation for spinal metastases epidural spinal cord compression (MESCC) and analyze the related factors of postoperative ambulation function. METHODS: Clinical data of 67 cases with MESCC who received thoracic posterior decompression and internal fixation in our department from January 2006 to December 2014 was retrospectively analyzed. Information about patients' age, gender, pathological type of primary tumor, Karnofsky performance status (KPS) score, pre-operative and postoperative visual analogue scale, preoperative Frankel grade, pre-operative and postoperative imaging characteristics (number of thoracic vertebrae metastases, location, compression fractures of vertebral bodies), time of movement dysfunction and survival was collected. RESULTS: At the end of the follow-up of 67 cases, 57 cases were dead, 10 cases were alive, and the median survival was 8.1 months (1.2-91.9 months).38 cases (67%) died within one year, 50 cases (88%) died within two years. Visual analogue scale of preoperative and postoperative dropped from (5.67+/-1.67) points to (2.11+/-1.39) points (P<0.001), 38 (53%) patients' Frankel grade improved at least one grade. Among the 34 cases who were unable to walk, 15 cases regained ability of ambulation after surgery. The patients with KPS scores greater than 80 points and/or had preoperative ambulation ability, tended to have better postoperative ambulatory function. CONCLUSIONS: Posterior decompression and internal fixation for MESCC is effective, and can effectively relieve pain and spinal cord compression, improve neurological function and the quality of life. The ambulatory functional outcomes after surgery are dependent on KPS scores, the occurrence time of neurological dysfunction, preoperative ambulatory status. PMID- 26902192 TI - [Changes of brain pain center and default mode network an electro acupuncture in Weizhong and Dachangshu acupoints: a task-fMRI study]. AB - OBJECTIVE: To investigate the functional brain pain center and default mode network response to electro acupuncture stimulate in weizhong acupoints(BL40) and dachangshu acupoints(BL25). METHODS: During January to February 2015, volunteers were enrolled in this study from the staff and student interns of Gansu Province Traditional Chinese Medicine Hospital. A total of 20 healthy, right-handed subjects, male 9, female 11, age (23+/-3) years, participated in this study. Block design task functional magnetic resonance imaging(fMRI) 3.0 T was performed in all subjects by electro acupuncture stimulating at BL40 and BL25 from the same experienced acupuncturist.The needle connected electric acupuncture apparatus through tow long coaxial-cable. A block design with five 120 s blocks of rest time (OFF block, electric acupuncture turn off ) interspersed between five 60 s blocks of stimulation (ON block, electric acupuncture turn on) fMRI scan. Magnetic resonance data of brain function was collected and FSL(fMRI Software Library) software was used to analyze the data. RESULTS: All subjects' data were analyzed except 2 cases whose head movement were more than 2 mm. Activated brain function regions by electro acupuncture stimulate included temporal lobe lateral sulcus, lobus insularis, thalamus, supramarginal gyrus, prefrontal medial frontal gyrus. Negative activated brain regions included middle frontal gyrus, parahippocampal gyrus, cingulate cortex abdominal segment, parietal cortex.The functional pain central and default mode network were changed when electro acupuncture stimulate in(BL40) and(BL25). CONCLUSION: There are several brain activation regions and negative activated brain regions when administering electro acupuncture stimulation at BL40 and BL25. PMID- 26902193 TI - [Observation of the clinical efficacy of tigecycline for treatment of ventilator associated pneumonia in critically ill elderly patients]. AB - OBJECTIVE: To evaluate the efficacy of tigecycline for treatment of ventilator associated pneumonia in critically ill elderly patients. METHODS: Data of critically ill elderly patients with ventilator-associated pneumonia treated with tigecycline in the intensive care unit was collected from June 2011 to March 2014 in this retrospective study, to evaluated the clinical efficacy of tigecycline. RESULTS: A total of 79 patients (83.5% male) were included, the mean age was 84 years old (rang, 65 years to 100 years old). Acinetobacter baumannii (39.1%), Pseudomonas aeruginosa (35.0%) and Klebsiella pneumonia (23.8%) were the most common pathogens.All patients were treated with tigecycline, 54.4% combined with other antimicrobial agents, 35.4% treated with double dose of tigecycline, and the mean course of antibiotic treatment was 9 days (range, 2 days to 22 days). After treatment, clinical success were recorded in 44 patients (55.7%), clinical failure were recorded in 29 patients, clinical uncertainty were recorded in 6 patients.28 days after treatment, patients' overall mortality was 39.0%.The clinical success rates were associated with acute physiology and chronic health evaluation (APACHE) II score less than 15 (the clinical success rates were 72.2% and 41.9% in patients with APACHE II score<15 and APACHE II score>=15, respectively; P=0.007); treated with double dose of tigecycline (71.4% vs 47.1%, P=0.037) or combination regimens were also had significant difference (67.4% vs 41.7%, P=0.022). CONCLUSIONS: Treatment of tigecycline combined with other antimicrobial agents and double dose of tigecycline may both can improve clinical efficacy in critically ill elderly patients with ventilator-associated pneumonia. PMID- 26902194 TI - [Efficacy for artery chemoembolization combined with radiofrequency ablation in the treatment of advanced non-small cell lung cancer]. AB - OBJECTIVE: To investigate efficacy and safety of artery chemoembolization combined with radiofrequency ablation for advanced non-small cell lung cancer. METHODS: A total of 138 cases of Sichuan Cancer Hospital of patients with advanced non-small cell lung cancer were retrospectively analyzed from January 2011 to November 2014.All cases were divided into three groups, 61 cases were treated by artery chemoembolization (ACB group), 43 cases were treated by artery chemoembolization combined with radiofrequency ablation (Joint group), 34 cases were treated by radiofrequency ablation (RFA group). Recent efficiency, overall survival time, adverse reactions and complications of three groups were analyzed. The risk factors related to survival time of 138 patients were analyzed. RESULTS: The recent efficiency of ACB group, Joint group and RFA group were 73.8%(45/61), 93.0%(40/43), 85.3%(29/34), respectively, and the difference was statistically significant (chi(2)=18.499, P=0.005). 1, 2, 3-year survival rates of Joint group were 90.7%(39/43), 58.1%(25/43), 20.9%(9/43), respectively that were better than ACB group(57.4%(35/61), 24.6%(15/61), 11.5%(7/61)) and RFA group(58.8%(20/34), 32.4%(11/34), 11.8%(4/34)), (chi(2) value were respectively 8.242 and 4.934, P values were 0.004 and 0.026). Chemotherapy side effects and complications of ablation were of no significant difference (P>0.05). Chemotherapy side effects and complications of ablation were of no significant difference (P>0.05). The number of tumors, tumor size, TNM staging, eastern cooperative oncology group (ECOG) score were independent risk factors which impact on survival time for non small cell lung cancer. The artery chemoembolization combined with radiofrequency ablation treatment can improve survival time of patients with advanced non-small cell lung cancer. CONCLUSION: Artery chemoembolization combined with radiofrequency ablation is a safe, effective, minimally-invasive treatment for advanced non-small cell lung cancer. PMID- 26902196 TI - [Management of 99 intracranial aneurysms in neurovascular hybrid operating room]. AB - OBJECTIVE: To analyze the current status of intracranial aneurysms treated in neurovascular hybrid operating room. METHODS: In the neurovascular hybrid operating room of New Era Stroke Care & Research Center, the Second Artillery General Hospital PLA, from October 2013 to November 2015, 99 cases of intracranial aneurysms were managed by interventional treatment, open surgery, hybrid surgery or switched surgical procedures. RESULTS: Patients with intracranial aneurysms treated in neurovascular hybrid operating room achieved good clinical outcome. CONCLUSION: It is an ideal option to treat intracranial aneurysms in neurovascular hybrid operating room. PMID- 26902195 TI - [Atypical MRI appearance of hepatic focal nodular hyperplasia]. AB - OBJECTIVE: To explore the atypical MRI findings of focal nodular hyperplasia (FNH) of the liver. METHODS: Retrospective analyses were conducted for 13 cases (10 males and 3 females) confirmed pathologically as FNH after surgery or biopsy with liver MRI examination from January 2012 to June 2015 in PLA General Hospital. RESULTS: There were 22 focal lesions in 12 cases, and diffuse pattern in 1 case. In the 22 focal lesions, there were 3 lesions with fatty change, 1 lesion with hemorrhage, 7 lesions with pseudo-capsule, regarding to dynamic contrast-enhanced pattern: 12/22 lesions with gradually increasing enhancement, 3/22 lesions with rapid wash-in and wash-out, and 7/22 lesions with rapid wash-in and slow wash-out. The hepatocyte-specific agent examinations were performed in 20/22 lesions, and 20/20 lesions showed iso- to hyper-intensity to the liver parenchyma in the hepatocyte phase.There was 1 case (female) showing diffuse lesions with obvious fatty change, and all the lesions took up the hepatocyte specific agent in hepatocyte phase. CONCLUSION: The atypical focal nodular hyperplasia often occurs in middle age males and could demonstrate fatty change, hemorrhage, pseudo-capsule, various enhancement patterns. And when the FNH showed atypical routine MRI findings, the use of the hepatocyte-specific agent could facilitate the diagnosis. PMID- 26902197 TI - [Diagnosis of benign peripheral neurilemmomas by ultrasound]. AB - OBJECTIVE: To investigate the peripheral nerve sheath tumors sonographic features. METHODS: It was a retrospective analysis of ultrasound images and clinical manifestations which were pathologically confirmed 31 cases of peripheral nerve sheath tumors in March 2011 to November 2014 from Xuanwu Hospital. RESULTS: In 14 cases of 31 patients were with a clinical touch and pressure pain, 17 cases showed superficial painless mass. Ultrasound showed hypoechoic nodules 30 cases, with an average size of (2.9 +/- 1.6) cm; encapsulated, border clearance, including 1 case of cystic part; color Doppler flow imaging ultrasound: no intralesional flow signals 21 patients (21/30 patients), a small amount of blood flow signals 9 cases (9/30 patients); 2 cases of multiple lesions. Another one case of preoperative ultrasound examination showed no echo, misdiagnosed as ganglion cyst. CONCLUSION: Hypoechoic encapsulated, border clearance, little or no blood flow is the main basis of ultrasound diagnosis schwannoma, in some cases, there may be cystic ultrasound, a small number of multiple lesions. PMID- 26902198 TI - [All-trans retinoic acid improves iodine uptake of thyroid cancer cells via repressing transcriptional activity of beta-catenin]. AB - OBJECTIVE: To determine whether all-trans retinoic acid (ATRA) could improve iodine uptake via repressing transcriptional activity of beta-catenin in thyroid cancer cells. METHODS: Three kinds of treatment models were firstly established with alcohol, ATRA, and transfection of beta-catenin shRNA in undifferentiated human thyroid cancer cell line-SW1736.Then the expressions of sodium iodide symporter (NIS), beta-catenin and its regulating factors, epithelial-mensechymal transition (EMT)-phenotype, invasion and metastasis associated proteins were further measured in above three cell models.After that, the influence of ATRA on the functional expression of NIS, iodine uptake potency, tumor growth curve and treatment effect inducing by radioactive iodine was comparatively analyzed in vitro and in vivo trials. RESULTS: After treated with ATRA, transcriptional activity of beta-catenin decreased by downregulating phosphorylation of beta catenin Ser45, Y654 and GSK-3beta Ser9. Additionally, ATRA effectively upregulated the protein level of NIS, and reversed EMT phenotype in alcohol treated cells, with absence in epithelial expression of E-cadherin and cytokeratin 18, as well as abnormal expression of Vimentin, urinary plasminogen activator (uPA), uPAR and Fibronectin.Compared with alcohol-treated group, both in vitro proliferation and invasion potential of ATRA treated cells markedly decreased (all P<0.05), and iodine uptake in vitro increased about 3.5-folds (P=0.007). In ATRA-treated animal model, tumor growth potential and tumor mass were significantly inhibited by radio-iodine ((131)I) treatment (all P<0.05). CONCLUSIONS: ATRA can increase functional expression of NIS via downregulating transcriptional activity of beta-catenin and promote isotope sensitivity to radio iodine in human undifferentiated thyroid cancer. PMID- 26902199 TI - [Efficiency of integrin alphavbeta3 inhibitor Cilengitide in acute cerebral ischemia in rats]. AB - OBJECTIVE: To explore the effect of the integrin alphavbeta3 inhibitor Cilengitide on the blood brain barrier (BBB) permeability, brain edema, neuronal cell apoptosis and the relation with the vascular endothelial growth factor (VEGF)expression in acute cerebral ischemia rats. METHODS: A rat focal cerebral ischemia/reperfusion model was established by middle cerebral artery occlusion. Rats with middle cerebral artery occlusion, in accordance with the random number table, were divided into four groups: (1) the rats in Cilengitide group A (n=30) were treated with Cilengitide at a dose of 100 MUg/kg; (2) the rats in Cilengitide group B (n=28) were treated with Cilengitide at a dose of 200 MUg/kg; (3) the rats in sham group (n=31), without inserting thread into middle cerebral artery, were treated with normal saline; (4) the rats in control group (n=27) were treated with normal saline.All rats were treated with Cilengitide or saline 1 hour after infarction, given reperfusion 2 hours after infarction and were sacrificed 22 hours after reperfusion.The brain-water content was measured by dry/wet weight method. The permeability of BBB was measured by quantifying Evans Blue. The infarction volume was measured by 2, 3, 5-tripheyl tetrazolium Chloride (TTC) staining. Expression level of VEGF, P-Flk, Cleaved-Caspase-3 was measured by immunohistochemistry and Western blot, respectively.The neuronal cell apoptosis was evaluated by terminal deoxynucleotidyl transferased UTP nick end labeling (TUNEL). RESULTS: Compared with Control group, treatment groups with cilengitide at the dose of 100 MUg/kg and 200 MUg/kg reduced brain-water content [(80.8+/-1.1)% vs (84.8+/-1.4)%, (81.0+/-1.4)% vs (84.8+/-1.4)%, P<0.05], reduced exudation of Evans blue[(9.2+/-1.1) MUg/g vs (12.2+/-0.8) MUg/g, (8.6+/-0.6) MUg/g vs (12.2+/-0.8) g/g, P<0.05], reduced infarction volume[(31.9+/-4.9) mm(3) vs(43.0+/-2.2) mm(3), (29.2+/-3.5) mm(3) vs(43.0+/-2.2) mm(3), P<0.05] , reduced neuronal cell apoptosis [(36+/-4)vs(69+/-6),(35+/-3)vs (69+/-6), P<0.05]. Compared with sham group, Cilengitide group A and Cilengitide group B had lower brain-water content, permeability of BBB, infarction volume, expression level of VEGF, P-Flk, Cleaved-Caspase-3 and neuronal cell apoptosis (P<0.05). When Cilengitide group A was compared with Cilengitide group B, there were no significant differences in brain-water content, permeability of BBB, infarction volume, expression level of VEGF, P-Flk, Cleaved-Caspase-3 and neuronal cell apoptosis (P>0.05). CONCLUSION: The integrin alphavbeta3 inhibitor Cilengitide improves outcomes in the MCAO model by preserving the blood-brain barrier, attenuating brain edema and inhibiting neuronal cell apoptosis, which may occur in a VEGF-and VEGF-receptor-dependent manner, with the same efficacy between Cilengitide 100 MUg/kg and 200 MUg/kg after 23 hours treatment. PMID- 26902200 TI - [Current status regarding the cardiovascular disease-related risk levels among the hypertensive population of different ethnicities in Xinjiang Uygur Autonomous Region, China]. AB - OBJECTIVE: To assess the status of the cardiovascular disease associated risk levels among hypertensive population of Han, Uygur and Kazakh ethnicities, in Xinjiang Uygur Autonornous Region, to guide hypertension prevention and treatment in different ethnicities. METHODS: Four stages random cluster sampling method was used, and all the data was collected from Xinjiang local residents aged over 18 between October 2007 and March 2010. RESULTS: A total of 14 618 subjects completed this survey, in which 2 654 Han, 1 612 Uygur and 2034 Kazakh people diagnosed with hypertension was included in this research. Most of them were"grade 1 hypertension", and the percentage of grade 3 hypertension was Han (19.1%), Uygur (17.3%) and Kazakh (32.3%), respectively. Majority hypertensive people accompanied with 1 risk factor. The risk proportions of low, medium, high and very high in hypertension population of different ethnicities were Han (19.4%, 34.6%, 46.1%), Uygur (17.7%, 37.6%, 44.7%), Kazakh (12.5%, 38.0%, 49.4%) respectively. In Han, Uygur and Kazakh ethnicities, the percentage of high risk and very high risk was highest in hypertensive men aged over 60 years old.The percentages of hypertension awareness were 42.0%, 45.6%, 46.5% and percentages of medicine therapy were 29.6%, 23.4%, 25.2% for Han, Uygur and Kazakh ethnicities, respectively. CONCLUSIONS: Hypertensive people among Han, Uygur and Kazakh ethnicities in Xinjiang are mainly under high risk and very high risk situation of cardiovascular disease, especially in men aged >=60. The percentage of hypertension awareness and medicine therapy in high risk and very high risk population is the highest, while percentage of awareness in medium risk population is low. PMID- 26902201 TI - [Effects of beta-blockers in patients with septic shock: a meta analysis]. AB - OBJECTIVE: To evaluate the effect of beta-blockers in patients with septic shock. METHODS: PubMed, EMBASE, Cochrane central registration of controlled trials, CNKI and Wanfang Data were searched to identify relevant studies from inception to October 2015.Statistical analysis was performed using STATA 12.0.The random effects model was used due to wide clinical variability across the trials. RESULTS: After application of the inclusion criteria, 7 trials with 392 patients were included, involving 3 randomized controlled trials (RCT) and 4 quasi experiments.The results of the meta-analysis for the quasi-experiments showed that compared with baseline, heart rates (standardized mean difference (SMD)= 2.51, 95%CI: -4.32--0.70, P=0.007) and lactate levels (SMD=-0.34, 95%CI: -0.67- 0.02, P=0.039) significantly decreased, while no significant differences were seen for mean arterial pressure (SMD=0.01, 95%CI: -0.42-0.44, P=0.969), cardiac index (SMD=-0.35, 95%CI: -1.15-0.44, P=0.385) or norepinephrine requirements (SMD=-0.06, 95%CI: -0.38-0.27, P=0.726) after 24-hour therapy. Among randomized controlled trials, beta-blockers, compared with standard care, was associated with reductions in heart rates (P<0.001) , 28-day mortality (RR=0.60, 95%CI: 0.48 0.75, P<0.001) and troponin I levels (P<0.001). While no differences were found between the two groups in other hemodynamic and cardiac function variables, such as mean arterial pressure, cardiac index or stroke volume index (P>0.05). CONCLUSIONS: The currently available evidence indicates that the use of beta blockers is associated with a significant decrease in heart rate, troponin I levels and 28-day mortality in patients with septic shock, while mean arterial pressure, cardiac index and stroke volume index might remain unchanged.Large scale, muti-center RCTs need to be carried out to confirm the effects of beta blockers in patients with septic shock. PMID- 26902203 TI - Splicing therapeutics for Alzheimer's disease. PMID- 26902202 TI - Mutations in pregnancy-associated plasma protein A2 cause short stature due to low IGF-I availability. AB - Mutations in multiple genes of the growth hormone/IGF-I axis have been identified in syndromes marked by growth failure. However, no pathogenic human mutations have been reported in the six high-affinity IGF-binding proteins (IGFBPs) or their regulators, such as the metalloproteinase pregnancy-associated plasma protein A2 (PAPP-A2) that is hypothesized to increase IGF-I bioactivity by specific proteolytic cleavage of IGFBP-3 and -5. Multiple members of two unrelated families presented with progressive growth failure, moderate microcephaly, thin long bones, mildly decreased bone density and elevated circulating total IGF-I, IGFBP-3, and -5, acid labile subunit, and IGF-II concentrations. Two different homozygous mutations in PAPPA2, p.D643fs25* and p.Ala1033Val, were associated with this novel syndrome of growth failure. In vitro analysis of IGFBP cleavage demonstrated that both mutations cause a complete absence of PAPP-A2 proteolytic activity. Size-exclusion chromatography showed a significant increase in IGF-I bound in its ternary complex. Free IGF-I concentrations were decreased. These patients provide important insights into the regulation of longitudinal growth in humans, documenting the critical role of PAPP-A2 in releasing IGF-I from its BPs. PMID- 26902205 TI - General Assessment of Humoral Activity in Healthy Humans. AB - The humoral immune system is network of biological molecules designed to maintain a healthy homeostatic equilibrium. Because antibodies are an abundant and highly specific effector of immunological action, they are also an important reservoir of previous host exposures. Antibodies may play a major role in early detection of host challenge. Unfortunately, few practical methods exist for interpreting the information stored in antibody variable regions. Immunosignatures use a microarray of thousands of random sequence peptides to interrogate antibodies in a broad and unbiased fashion. The pattern of binding between antibody and peptide is reproducible. Once the system has been trained on a disease cohort, blinded samples can be reliably predicted. Although immunosignatures of both chronic and infectious disease have been extensively tested, less has been done to demonstrate how healthy immunosignatures change over time or between individuals. Here, we report the results of a study of immunosignatures of healthy persons over brief (12 h sampled once per hour), intermediate (32 days sampled once per day), and long (5 years sampled once every year) time spans. Using this information, we were also able to detect intentional and unintentional immunological perturbations in the form of a vaccine and an infection, respectively. Our findings suggest that, even with the variability inherent in healthy immunosignatures, a single person's immunosignature will remain constant over time. Over this healthy signature, vaccines and infections create subsignatures that are common across multiple people, even subsuming healthy fluctuations. These findings have implications for disease monitoring and early diagnosis. PMID- 26902204 TI - Therapeutic correction of ApoER2 splicing in Alzheimer's disease mice using antisense oligonucleotides. AB - Apolipoprotein E receptor 2 (ApoER2) is an apolipoprotein E receptor involved in long-term potentiation, learning, and memory. Given its role in cognition and its association with the Alzheimer's disease (AD) risk gene, apoE, ApoER2 has been proposed to be involved in AD, though a role for the receptor in the disease is not clear. ApoER2 signaling requires amino acids encoded by alternatively spliced exon 19. Here, we report that the balance of ApoER2 exon 19 splicing is deregulated in postmortem brain tissue from AD patients and in a transgenic mouse model of AD To test the role of deregulated ApoER2 splicing in AD, we designed an antisense oligonucleotide (ASO) that increases exon 19 splicing. Treatment of AD mice with a single dose of ASO corrected ApoER2 splicing for up to 6 months and improved synaptic function and learning and memory. These results reveal an association between ApoER2 isoform expression and AD, and provide preclinical evidence for the utility of ASOs as a therapeutic approach to mitigate Alzheimer's disease symptoms by improving ApoER2 exon 19 splicing. PMID- 26902208 TI - International Association of Breath Research 10th anniversary conference at the Schoenbrunn Palace in Vienna, Austria. PMID- 26902206 TI - Systematic Analysis of Intracellular-targeting Antimicrobial Peptides, Bactenecin 7, Hybrid of Pleurocidin and Dermaseptin, Proline-Arginine-rich Peptide, and Lactoferricin B, by Using Escherichia coli Proteome Microarrays. AB - Antimicrobial peptides (AMPs) act either through membrane lysis or by attacking intracellular targets. Intracellular targeting AMPs are a resource for antimicrobial agent development. Several AMPs have been identified as intracellular targeting peptides; however, the intracellular targets of many of these peptides remain unknown. In the present study, we used an Escherichia coli proteome microarray to systematically identify the protein targets of three intracellular targeting AMPs: bactenecin 7 (Bac7), a hybrid of pleurocidin and dermaseptin (P-Der), and proline-arginine-rich peptide (PR-39). In addition, we also included the data of lactoferricin B (LfcinB) from our previous study for a more comprehensive analysis. We analyzed the unique protein hits of each AMP in the Kyoto Encyclopedia of Genes and Genomes. The results indicated that Bac7 targets purine metabolism and histidine kinase, LfcinB attacks the transcription related activities and several cellular carbohydrate biosynthetic processes, P Der affects several catabolic processes of small molecules, and PR-39 preferentially recognizes proteins involved in RNA- and folate-metabolism-related cellular processes. Moreover, both Bac7 and LfcinB target purine metabolism, whereas LfcinB and PR-39 target lipopolysaccharide biosynthesis. This suggested that LfcinB and Bac7 as well as LfcinB and PR-39 have a synergistic effect on antimicrobial activity, which was validated through antimicrobial assays. Furthermore, common hits of all four AMPs indicated that all of them target arginine decarboxylase, which is a crucial enzyme for Escherichia coli survival in extremely acidic environments. Thus, these AMPs may display greater inhibition to bacterial growth in extremely acidic environments. We have also confirmed this finding in bacterial growth inhibition assays. In conclusion, this comprehensive identification and systematic analysis of intracellular targeting AMPs reveals crucial insights into the intracellular mechanisms of the action of AMPs. PMID- 26902209 TI - The First Fatal Case of Crimean-Congo Hemorrhagic Fever Caused by the AP92-Like Strain of the Crimean-Congo Hemorrhagic Fever Virus. PMID- 26902207 TI - Tissue-specific Proteogenomic Analysis of Plutella xylostella Larval Midgut Using a Multialgorithm Pipeline. AB - The diamondback moth, Plutella xylostella (L.), is the major cosmopolitan pest of brassica and other cruciferous crops. Its larval midgut is a dynamic tissue that interfaces with a wide variety of toxicological and physiological processes. The draft sequence of the P. xylostella genome was recently released, but its annotation remains challenging because of the low sequence coverage of this branch of life and the poor description of exon/intron splicing rules for these insects. Peptide sequencing by computational assignment of tandem mass spectra to genome sequence information provides an experimental independent approach for confirming or refuting protein predictions, a concept that has been termed proteogenomics. In this study, we carried out an in-depth proteogenomic analysis to complement genome annotation of P. xylostella larval midgut based on shotgun HPLC-ESI-MS/MS data by means of a multialgorithm pipeline. A total of 876,341 tandem mass spectra were searched against the predicted P. xylostella protein sequences and a whole-genome six-frame translation database. Based on a data set comprising 2694 novel genome search specific peptides, we discovered 439 novel protein-coding genes and corrected 128 existing gene models. To get the most accurate data to seed further insect genome annotation, more than half of the novel protein-coding genes, i.e. 235 over 439, were further validated after RT PCR amplification and sequencing of the corresponding transcripts. Furthermore, we validated 53 novel alternative splicings. Finally, a total of 6764 proteins were identified, resulting in one of the most comprehensive proteogenomic study of a nonmodel animal. As the first tissue-specific proteogenomics analysis of P. xylostella, this study provides the fundamental basis for high-throughput proteomics and functional genomics approaches aimed at deciphering the molecular mechanisms of resistance and controlling this pest. PMID- 26902210 TI - Analysis of Death Due to Infectious Diseases in Patients Hospitalized in the Pediatric Ward of a Single Japanese Tertiary Medical Facility. AB - In developed countries, the infection related-mortality rates in children hospitalized in tertiary medical facilities, where many patients with underlying disease are also hospitalized, are uncertain. We investigated the characteristics of infectious diseases-related fatal cases in the pediatric ward of a Japanese tertiary medical facility. A total of 188 patients who died in the pediatric ward or intensive care unit at Kyushu University Hospital from 2002 to 2011 were enrolled. The patient characteristics were investigated based on their medical records. A total of 35 patients died of infections, 31 of whom had underlying diseases. Most patients died of sepsis or pneumonia (n = 27). All 9 patients who died within 7 days of birth were premature. Nine of the 13 patients with malignancy or hematological disorders died of hematopoietic stem cell transplantation (HSCT)-associated infections. The ratio of infectious disease related fatal cases to the total cases decreased in the latter half of the study period. In particular, the proportion of preterm infants who died of infections was significantly lower in the latter 5 years (p = 0.02). Many of the infectious disease-related fatal cases were in premature infants and HSCT or post-HSCT patients. However, the mortality due to infectious diseases decreased in these patient groups. PMID- 26902211 TI - A Rapid and Simple Real-Time PCR Assay for Detecting Foodborne Pathogenic Bacteria in Human Feces. AB - A rapid, simple method for detecting foodborne pathogenic bacteria in human feces is greatly needed. Here, we examined the efficacy of a method that employs a combination of a commercial PCR master mix, which is insensitive to PCR inhibitors, and a DNA extraction method which used sodium dodecyl benzene sulfonate (SDBS), and Tween 20 to counteract the inhibitory effects of SDBS on the PCR assay. This method could detect the target genes (stx1 and stx2 of enterohemorrhagic Escherichia coli, invA of Salmonella Enteritidis, tdh of Vibrio parahaemolyticus, gyrA of Campylobacter jejuni, ceuE of Campylobacter coli, SEA of Staphylococcus aureus, ces of Bacillus cereus, and cpe of Clostridium perfringens) in a fecal suspension containing 1.0 * 101 to 1.0 * 103 CFU/ml. Furthermore, the assay was neither inhibited nor influenced by individual differences among the fecal samples of 10 subjects or fecal concentration (40-160 mg/ml in the fecal suspension). When we attempted to detect the genes of pathogenic bacteria in 4 actual clinical cases, we found that this method was more sensitive than standard culture method. These results showed that this assay is a rapid, simple detection method for foodborne pathogenic bacteria in human feces. PMID- 26902212 TI - Detection of Human Parechoviruses in Clinical and Municipal Wastewater Samples in Miyagi, Japan, in 2012-2014. AB - In order to study the epidemiology of human parechovirus (HPeV) infections and to evaluate the feasibility of environmental surveillance, we analyzed 281 stool samples, 265 nasopharyngeal swab samples, and 79 municipal wastewater samples for HPeV. The samples were collected in Miyagi Prefecture, Japan, between April 2012 and March 2014. HPeV was detected by reverse-transcription-PCR targeting the partial 5'-untranslated region and was genotyped by sequencing the capsid VP1 region. Seven stool samples (2.5%) and 1 nasopharyngeal swab sample (0.4%), all of which were from children under 2 years old, and 14 wastewater samples (18%) were positive for HPeV. Clear seasonality was observed: all positive samples were collected between July and December during the study period. All strains detected in the stool and wastewater samples had genotype HPeV1, and the strain from the nasopharyngeal swab sample had genotype HPeV6. A phylogenetic analysis revealed that all HPeV1 strains from the stool samples cluster together with those from the wastewater samples, indicating that the HPeV1 strains circulating in human populations can also be detected in municipal wastewater. PMID- 26902213 TI - Characterization of Shiga Toxin-Producing Escherichia coli Isolated from Humans between 2011 and 2014. AB - Although E. coli O157:H7 is the major serotype among Shiga toxin-producing Escherichia coli (STEC) strains, non-O157 serotypes have caused numerous outbreaks worldwide. We aimed to evaluate the distribution of serogroups, serotypes, virulence genes, and antimicrobial resistance of STEC strains recovered from stool samples. A total of 395 stool samples characterized by watery/bloody diarrhea and/or symptoms of hemolytic-uremic syndrome were included in this study. Strains compatible with E. coli, based on biochemical tests, were tested for the presence of Shiga toxin by ELISA. Toxigenic strains were tested by serotyping and serogrouping. Virulence genes, stx1, stx2, aggR, hlyA, and eae were detected by polymerase chain reaction. Overall, 26 (6.6%) stool culture samples tested positive for STEC. Shiga toxin was positive in 28 (7.1%) patient isolates based on ELISA and PCR. Two isolates could not be serotyped. STEC strains were distributed into 10 serogroups and 14 serotypes. Of the serotyped strains, 92.3% were non-O157, with the major distribution in O104:H4 and O26:HNM. All were negative for extended-spectrum beta-lactamase enzyme and 62.5% were resistant to at least 1 drug. This study demonstrated the wide distribution of non-O157 STEC strains from our patient group. Further studies should be performed to better understand STEC characteristics on a larger scale. PMID- 26902214 TI - Contribution of Lewis X Carbohydrate Structure to Neuropathogenic Murine Coronaviral Spread. AB - Although Lewis X (Le(x)), a carbohydrate structure, is involved in innate immunity through cell-to-cell and pathogen recognition, its expression has not been observed in mouse monocytes/macrophages (Mo/Mas). The Mo/Mas that infiltrate the meninges after infection with the neuropathogenic murine coronavirus strain srr7 are an initial target of infection. Furthermore, higher inflammatory responses were observed in gene-manipulated mice lacking alpha1,3 fucosyltransferase 9, which determines the expression of the Le(x) structure, than in wild type mice after infection. We investigated Le(x) expression using CD11b-positive peritoneal exudate cells (PECs) and found that Le(x) is inducible in Mo/Mas after infection with srr7, especially in the syncytial cells during the late phase of infection. The number of syncytial cells was reduced after treatment of the infected PECs with anti-Le(x) antibody, during the late phase of infection. In addition, the antibody treatment induced a marked reduction in the number of the infected cells at 24 hours post inoculation, without changing the infected cell numbers during the initial phase of infection. These data indicate that the Le(x) structure could play a role in syncytial formation and cell-to cell infection during the late phase of infection. PMID- 26902215 TI - In Vitro Inhibition of Cholera Toxin Production in Vibrio cholerae by Methanol Extract of Sweet Fennel Seeds and Its Components. AB - A newly emerged Vibrio cholerae O1 El Tor variant strain with multidrug resistance is considered a threat to public health. Recent strategies to suppress virulence factors production instead of bacterial growth may lead to less selective pressure for the emergence of resistant strains. The use of spices and their active constituents as the inhibitory agents against cholera toxin (CT) production in V. cholerae may be an alternative approach to treat cholera. In this study, we examined the potential of sweet fennel seed (Foeniculum vulgare Miller var. dulce) methanol extract to inhibit CT production in V. cholerae without affecting viability. The methanol extract of sweet fennel seeds significantly inhibited CT production in various V. cholerae strains, regardless of serogroup or biotype. Interestingly, trans-anethole and 4-allylanisole, essential oil components of sweet fennel seeds, also demonstrated similar effects. Here, we report that sub-bactericidal concentrations of sweet fennel seed methanol extract and its major components can drastically inhibit CT production in various V. cholerae strains. PMID- 26902216 TI - Prevalence and Virulence Genes of Shigella spp. Isolated from Patients with Diarrhea in Rosario, Argentina. AB - The aim of this study was to determine the prevalence and virulence factors of Shigella species isolated from patients with diarrhea. Shigella species were isolated from 1,022 stool samples collected from different hospitals in Rosario, Argentina. The isolates were characterized using phenotypic tests, serotyping, and detection of virulence genes by PCR. One hundred strains (9.8% of samples collected) of Shigella were isolated. Shigella flexneri was the most frequently identified species (74%), followed by S. sonnei (26%). S. flexneri was also the predominant species isolated from children aged 6-14 years. These clinical strains of Shigella were then tested for the presence of ipaH, virA, ial, sen, and set using specific primers. virA was present in all strains, whereas ipaH was detected in 98% of strains and ial in 83%. sen was found in 71.6% of S. flexneri and 42.3% of S. sonnei isolates, and 41.9% of S. flexneri isolates were positive for set. Furthermore, 32.4% of S. flexneri isolates were positive for both set and sen. This study provides data on the prevalence and distribution of diverse Shigella strains. PMID- 26902217 TI - Carbapenemase-Producing Enterobacteriaceae in Yunnan Province, China. AB - Among 144 carbapenem-resistant Enterobacteriaceae strains isolated from 4 hospitals in Yunnan province, 113 were identified as carbapenemase-producing Enterobacteriaceae (CPE). BlaKPC-2 (99/113, 87.6%) was the most common carbapenemase gene and Klebsiella pneumoniae (100/113, 88.5%) was the most common species. BlaNDM-1 (11/113, 9.7%), blaIMP-4 (10/113, 8.8%), and blaIMP-1 (1/113, 0.9%) genes were also detected. Extended-spectrum beta-lactamase genes were common in CPE, and the SHV- and CTX-M-types were predominant. PMID- 26902218 TI - Catheter-Related Bacteremia Due to Gordonia sputi in a Patient with Acute Lymphocytic Leukemia: a Case Report. PMID- 26902219 TI - Use of Peripheral Parenteral Nutrition Solutions as a Risk Factor for Bacillus cereus Peripheral Venous Catheter-Associated Bloodstream Infection at a Japanese Tertiary Care Hospital: a Case-Control Study. AB - The risk factors are unclear for peripheral venous catheter-associated bloodstream infections (PVCBSIs) caused by Bacillus cereus. We aimed to examine for these risk factors in patients with B. cereus PVCBSI by conducting a 2-year case-control study in a large teaching hospital. We analyzed all adult cases of B. cereus PVCBSI (37 patients) and 180 controls who were randomly selected from among patients who had a PVC in place for at least 2 days. Multivariate analysis using a conditional logistic regression model indicated that independent risk factors were use of a peripheral parenteral nutrition (PPN) solution with an adjusted odds ratio (OR) of 88.7 (95% confidence interval [CI], 17.4-451.9), and steroid therapy (adjusted OR, 5.7 [95% CI, 1.3-24.4]). In conclusion, use of PPN solutions or steroids was an independent risk factor for B. cereus PVCBSI. Appropriate use of PPN solutions may help prevent B. cereus PVCBSI. Prospective studies are needed to confirm these results. PMID- 26902220 TI - Influence of Average Income on Epidemics of Seasonal Influenza. AB - Understanding the local factors influencing the transmission of communicable diseases is important to minimize social damage. The aim of this study was to investigate local factors influencing seasonal influenza epidemics in Aomori prefecture consisting of 6 regions, i.e., Seihoku, Chunan, and Tosei on the west side, and Sanpachi, Kamikita, and Shimokita on the east side. Four indices (epidemic onset, duration, scale, and steepness of epidemic curves) were defined, and their correlations with regional characteristics and meteorological factors were investigated. Data for influenza seasons from 2006-2007 to 2014-2015 were collected. The 2009-2010 season was excluded because of the pandemic of A (H1N1)pdm09. Average income was strongly correlated with epidemic onset, duration, and scale. The ratio of children aged <=5 years to the total population was strongly correlated with epidemic duration and scale. Low temperature in January showed moderate correlation with epidemic duration and scale. Cluster analysis showed that 2 isolated regions, Seihoku and Chunan, belonged to the same cluster in the 4 indices of epidemic curves, and other 2 relatively urbanized regions formed another cluster in 3 of the 4 indices. This study highlights important local factors that influence seasonal influenza epidemics and may help in implementation of preventive measures. PMID- 26902221 TI - Current Status of Condylomata Acuminata in Pregnant Japanese Women. PMID- 26902222 TI - Chance Isolation of Non-Pathogenic Vaccine-Derived Measles and Rubella Viruses from Children with Acute Respiratory Infections. PMID- 26902223 TI - Cross-Neutralization Activity of Single-Chain Variable Fragment (scFv) Derived from Anti-V3 Monoclonal Antibodies Mediated by Post-Attachment Binding. AB - The V3 loop in the envelope (Env) of HIV-1 is one of the major targets of neutralizing antibodies. However, this antigen is hidden inside the Env trimer in most isolates and is fully exposed only during CD4-gp120 interaction. Thus, primary HIV-1 isolates are relatively resistant to anti-V3 antibodies because IgG is too large to access the V3 loop. To overcome this obstacle, we constructed single-chain variable fragments (scFvs) from anti-V3 monoclonal antibodies 0.5gamma, 5G2, and 16G6. Enhanced neutralization by 0.5gamma and 5G2 scFvs was observed in strains resistant to their IgG counterparts. Neutralization coverage by 0.5gamma scFv reached up to 90% of the tested viruses (tier 2 and 3 classes). The temperature-regulated neutralization assay revealed that extensive cross neutralization of 0.5gamma scFv can be explained by post-attachment neutralization. Neutralization assay involving viruses carrying an inter-subunit disulfide bond (SOS virus) showed that the neutralization-susceptible timeframe after attachment was 60 to 120 min. These results indicate that the scFvs efficiently access the V3 loop and subsequently neutralize HIV-1, even after virus attachment to the target cells. Based on its broad and potent neutralizing activity, further development of anti-V3 scFv for therapeutic and preventive strategies is warranted. PMID- 26902224 TI - Fad24, a Positive Regulator of Adipogenesis, Is Required for S Phase Re-entry of C2C12 Myoblasts Arrested in G0 Phase and Involved in p27(Kip1) Expression at the Protein Level. AB - Factor for adipocyte differentiation 24 (fad24) is a positive regulator of adipogenesis. We previously found that human fad24 is abundantly expressed in skeletal muscle. However, the function of fad24 in skeletal muscle remains largely unknown. Because skeletal muscle is a highly regenerative tissue, we focused on the function of fad24 in skeletal muscle regeneration. In this paper, we investigated the role of fad24 in the cell cycle re-entry of quiescent C2C12 myoblasts-mimicked satellite cells. The expression levels of fad24 and histone acetyltransferase binding to ORC1 (hbo1), a FAD24-interacting factor, were elevated at the early phase of the regeneration process in response to cardiotoxin-induced muscle injury. The knockdown of fad24 inhibited the proliferation of quiescent myoblasts, whereas fad24 knockdown did not affect differentiation. S phase entry following serum activation is abrogated by fad24 knockdown in quiescent cells. Furthermore, fad24 knockdown cells show a marked accumulation of p27(Kip1) protein. These results suggest that fad24 may have an important role in the S phase re-entry of quiescent C2C12 cells through the regulation of p27(Kip1) at the protein level. PMID- 26902225 TI - Effects of Psoralen as an Anti-tumor Agent in Human Breast Cancer MCF-7/ADR Cells. AB - Psoralen is a major active component of Psoralea corylifolia. In the present study, we analyzed psoralen-induced changes in human breast cancer MCF-7/ADR cells and investigated the underlying mechanisms of the anticancer effect on MCF 7/ADR cells. We measured cell viability by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay to evaluate the cytotoxicity and multidrug resistance (MDR) reversal activity of psoralen. The cell cycle distribution and apoptosis, accumulation and efflux of rhodamine123 (Rh123), and P-glycoprotein (P-gp) expression levels of MCF-7/ADR cells treated with psoralen were all detected by flow cytometry (FCM). We assessed P-gp ATPase activity by monitoring ATP consumption. We evaluated the activity of nuclear factor-kappaB (NF-kappaB) and the expression of E-cadherin, vimentin and alpha-smooth muscle actin (SMA) involved in regulating epithelial-mesenchymal transition (EMT). The results showed that psoralen inhibited the proliferation of MCF-7/ADR cells as shown by G0/G1 phase arrest rather than encouraging apoptosis. It was also observed that psoralen reversed MDR through inhibiting ATPase activity rather than reducing P-gp expression. Our results further showed that psoralen inhibited the migration abilities of MCF-7/ADR cells by repressing EMT possibly through inhibiting the activation of NF-kappaB. Our findings provided a systematic and detailed description of the anti-cancer effect of psoralen on MCF-7/ADR cells for the exploration of natural compounds as novel anticancer agents. PMID- 26902227 TI - Breath Testing for Small Intestinal Bacterial Overgrowth: Should We Bother? AB - The hydrogen breath test is based on following breath hydrogen levels after the administration of a carbohydrate (most commonly lactulose) to a patient with suspected small intestinal bacterial overgrowth. The test is based on the interaction between the administered carbohydrate and the intestinal bacteria. The resulting fermentation produces hydrogen. A positive breath test is based on a breath hydrogen rise prior to the expected arrival time in the highly microbial cecum. Despite renewed enthusiasm for breath testing in recent years due to associations with conditions such as irritable bowel syndrome, breath testing poses many challenges. In this argument against breath testing, several pitfalls that complicate breath testing will be described. PMID- 26902226 TI - Gut Bacterial DNA Translocation is an Independent Risk Factor of Flare at Short Term in Patients With Crohn's Disease. AB - OBJECTIVES: We aimed at evaluating bacterial DNA (bactDNA) presence in blood of Crohn's disease (CD) patients in remission as an independent risk factor of flare at 6 months. METHODS: This is a prospective, multicenter study on CD patients with Crohn's disease activity index (CDAI)<150. The primary end point was time-to relapse as evaluated by CDAI>150 in the following 6 months. BactDNA in blood, the nucleotide-binding oligomerization domain containing 2 (NOD2) genotype, and serum cytokine levels were determined at baseline. RESULTS: A total of 288 patients were included. BactDNA was detected in 98 patients (34.0%). A variant-NOD2 genotype was identified in 114 patients (39.6%). Forty patients (14%) relapsed during follow-up. Multivariate survival analysis identified bactDNA as an independent risk factor of flare (hazard ratio (HR) 8.75 (4.02-19.06) 95% confidence interval (CI)). Hospitalization, surgery, switch of treatment, initiation and escalation of anti-tumor necrosis factor (TNF) therapy, steroids initiation, and increased fecal calprotectin levels at 6 months were associated with bactDNA at baseline. A logistic regression analysis showed bactDNA as an independent and significant predictive factor of hospitalization (odds ratio (OR) 11.9 (3.4-42.3); P<0.001), steroids startup (OR 8.5 (2.7-27.1); P<0.001), and switch of treatment (OR 3.5 (1.6-7.7); P=0.002) at 6 months. No relationship was observed between bactDNA and mucosal lesions in patients with colonoscopy at admission. Serum pro-inflammatory cytokines were significantly increased in patients with bactDNA or a variant-NOD2 genotype. The combination of both factors induced decreased anti-TNF-alpha levels and a higher percentage of patients on intensified anti-TNF therapy. CONCLUSIONS: BactDNA is an independent risk factor of relapse at 6 months in CD patients. BactDNA is also independently associated with an increased risk of hospitalization, switch of treatment, and steroids initiation. PMID- 26902228 TI - Esophageal Squamous Dysplasia is Common in Asymptomatic Kenyans: A Prospective, Community-Based, Cross-Sectional Study. AB - OBJECTIVES: Esophageal squamous cell carcinoma (ESCC) is endemic in east Africa and is a leading cause of cancer death among Kenyans. The asymptomatic precursor lesion of ESCC is esophageal squamous dysplasia (ESD). We aimed to determine the prevalence of ESD in asymptomatic adult residents of southwestern Kenya. METHODS: In this prospective, community-based, cross-sectional study, 305 asymptomatic adult residents completed questionnaires and underwent video endoscopy with Lugol's iodine chromoendoscopy and mucosal biopsy for detection of ESD. RESULTS: Study procedures were well tolerated, and there were no adverse events. The overall prevalence of ESD was 14.4% (95% confidence interval (CI): 10-19%), including 11.5% with low-grade dysplasia and 2.9% with high-grade dysplasia. The prevalence of ESD was >20% among men aged >50 years and women aged >60 years. Residence location was significantly associated with ESD (Zone A adjusted odds ratio (OR) 2.37, 95% CI: 1.06-5.30 and Zone B adjusted OR 2.72, 95% CI: 1.12 6.57, compared with Zone C). Iodine chromoendoscopy with biopsy of unstained lesions was more sensitive than white-light endoscopy or random mucosal biopsy for detection of ESD and had 67% sensitivity and 70% specificity. CONCLUSIONS: ESD is common among asymptomatic residents of southwestern Kenya and is especially prevalent in persons aged >50 years and those living in particular local regions. Lugol's iodine chromoendoscopy is necessary for detection of most ESD but has only moderate sensitivity and specificity in this setting. Screening for ESD is warranted in this high-risk population, and endoscopic screening of Kenyans is feasible, safe, and acceptable, but more accurate and less invasive screening tests are needed. PMID- 26902230 TI - The pharmacokinetics of vancomycin in patients with severe acute pancreatitis. AB - OBJECTIVE: The aim of this study was to evaluate the pharmacokinetics of vancomycin in patients with severe acute pancreatitis (SAP). METHODS: Sixty-seven patients with SAP were included. The FPIA method was used to measure vancomycin serum trough concentrations, and the pharmacokinetic parameters were calculated using the Bayesian estimator. Comparisons of mean values were analyzed using SPSS 11.0. RESULTS: The average daily dose of vancomycin was 15.0 +/- 3.7 mg/kg (q 12 h). Sixty-seven trough concentrations were collected. Compared with the recommended standard vancomycin trough concentration (15 mg/L), SAP patients had significantly lower vancomycin trough concentrations (6.1 +/- 3.0 mg/L; p < 0.0001) while the volume of distribution (Vd) and clearance (CL) of vancomycin were significantly increased. Multiple regression analysis revealed that vancomycin trough concentration was strongly correlated not only with age and albumin but also with the duration from SAP onset to vancomycin therapy (p < 0.0001). Stepwise regression analysis revealed that the duration was the most important variable for vancomycin trough concentration (r (2) = 0.456). The relationships between vancomycin trough concentrations and the duration were further evaluated after the 67 patients were stratified into two groups according to the duration from SAP onset to vancomycin therapeutic drug monitoring (TDM) within or over 4 weeks. Early group had much lower trough concentrations compared to late group, and the CL was also significantly increased in the early group. Of these 67 patients, 24 patients made vancomycin dosage adjustment (increased to 18.5 +/- 3.9 mg/kg, q 12 h) and the average trough concentrations increased to 12.6 +/- 3.8 mg/L. CONCLUSIONS: The serum trough concentration of vancomycin was significantly reduced in SAP patients. Higher dosage regimens are needed to ensure the clinical effect. PMID- 26902229 TI - Capnographic Monitoring in Routine EGD and Colonoscopy With Moderate Sedation: A Prospective, Randomized, Controlled Trial. AB - OBJECTIVES: Regulatory changes requiring the use of capnographic monitoring for endoscopic procedures using moderate sedation have placed financial challenges on ambulatory and hospital endoscopy centers across the United States due to the increased cost of training endoscopy personnel and purchasing both capnography monitoring devices and specialized sampling ports. To date, there has been no published data supporting the use of capnographic monitoring in adult patients undergoing routine endoscopic procedures with moderate sedation. The aim of this randomized, parallel group assignment trial was to determine whether intervention based on capnographic monitoring improves detection of hypoxemia in patients undergoing routine esophagogastroduodenoscopy (EGD) or colonoscopy with moderate sedation. METHODS: Healthy patients (ASA Physical Classification (ASAPS) I and II)) scheduled for routine outpatient EGD or colonoscopy under moderate sedation utilizing opioid and benzodiazepine combinations were randomly assigned to a blinded capnography alarm or open capnography alarm group. In both study arms, standard cardiopulmonary monitoring devices were utilized with additional capnographic monitoring. The primary end point was the incidence of hypoxemia defined as a fall in oxygen saturation (SaO2) to <90% for >=10 s. Secondary outcomes included severe hypoxemia, apnea, disordered respirations, hypotension, bradycardia, and early procedure termination for any cause. RESULTS: A total of 452 patients were randomized; 218 in the EGD and 234 in the colonoscopy groups; 75 subjects in the EGD group (35.9%) and 114 patients (49.4%) in the colonoscopy group were male, and average body mass index was 27.9 and 29.1 (kg/m(2)), respectively. The blinded and open alarm groups in each study arm were similar in regards to use of opioids and/or benzodiazepines and ASAPS classification. There was no significant difference in rates of hypoxemia between the blinded and open capnography arms for EGD (54.1% vs. 49.5; P=0.5) or colonoscopy (53.8 vs. 52.1%; P=0.79). CONCLUSIONS: Capnographic monitoring in routine EGD or colonoscopy for ASAPS I and II patients does not reduce the incidence of hypoxemia (ClinicalTrials.gov number, NCT01994785). PMID- 26902231 TI - A Review of Research on Health Outcomes for Workers, Home and Host Communities of Population Mobility Associated with Extractive Industries. AB - With a growing awareness of the association between extractive industries, the nature of work in remote locations, population mobility and health status, there is a need to advance an evidence-based approach to ensuring the health of migrant and mobile populations, and the home and host communities with whom they interact. Through a narrative synthesis of peer-reviewed and grey literature, this review examines what is known, and the nature of research activity concerning the range of health impacts determined by the social conditions inherent with population mobility alongside mining and extractive industries; and the extent to which health outcomes impact on workers, and home and host communities. While much of the literature reviewed in the study considered health in a traditional disease or illness based approach, it is clear that many risk factors for the health of mobile workers in the sector reflect broader social determinants. To support the mitigation of individual and population vulnerability to infectious disease endemics, consideration of both the etiology and the social conditions that give rise to adverse health outcomes is required, including an improvement to workers' living conditions, the expansion of diagnostic and medical services, and an approach that ensures the right to health for mobile populations. To further improve upon the rich body of research, resources are required to implement robust data collection including epidemiological surveillance, outbreak monitoring and investigation, and the long term tracking of standardized health information at both origin locations and destination communities. PMID- 26902232 TI - Levetiracetam associated acute hepatic failure requiring liver transplantation: case report. PMID- 26902234 TI - A research agenda for establishing the validity of non-academic assessments of medical school applicants. PMID- 26902233 TI - Time trend of cadmium intake in Korea. AB - OBJECTIVES: The aim of this study was to elucidate past and current levels of cadmium (Cd) intake among the general populations in Korea. METHODS: For this purpose, publications reporting dietary intake of cadmium (Cd-D), cadmium concentration in blood (Cd-B) and that in urine (Cd-U) in Korea were retrieved through literature survey for a period from 1975 to 2015. RESULTS: In practice, 9, 21 and 14 articles were available on Cd-D, Cd-B and Cd-Ucr (Cd-U as corrected for creatinine concentration), respectively. Linear regression analyses of the reported values as a function of years (i.e., the year when each survey was conducted) showed steady decreases in all of the three exposure markers of Cd-D, Cd-B and Cd-U(cr). Factors possibly contributing for the reduction were discussed including the government-set guideline of 0.2 mg/kg for rice and changes in food habits among general populations. CONCLUSIONS: There have been steady decreases in Cd-D, Cd-B and Cd-U(cr). The current estimates for Cd-D, Cd-B and Cd-Ucr were 6.0-7.4 MUg/day, 0.73-0.83 MUg/L and 0.60-0.95 MUg/g cr, respectively. PMID- 26902235 TI - Is prosopagnosia a clinical feature of heterotopia? Evidence from a single case report. PMID- 26902237 TI - Pneumocystis Jirovecii Presenting as Nodular Pulmonary Opacities. PMID- 26902236 TI - Predictors of Pharmacotherapy for Tobacco Use Among Veterans Admitted for COPD: The Role of Disparities and Tobacco Control Processes. AB - BACKGROUND: Many smokers admitted for chronic obstructive pulmonary disease (COPD) are not given smoking cessation medications at discharge. The reasons behind this are unclear, and may reflect an interplay of patient characteristics, health disparities, and the receipt of inpatient tobacco control processes. OBJECTIVES: We aimed to assess potential disparities in treatment for tobacco use following discharge for COPD, examined in the context of inpatient tobacco control processes. PARTICIPANTS: Smokers aged >= 40 years, admitted for treatment of a COPD exacerbation within the VA Veterans Integrated Service Network 20, identified using ICD-9 discharge codes and admission diagnoses from 2005-2012. MAIN MEASURES: The outcome was any tobacco cessation medication dispensed within 48 hours of discharge. We assessed potential predictors administratively up to 1 year prior to admission. We created the final logistic regression model using manual model building, clustered by site. Variables with p < 0.2 in biviariate models were considered for inclusion in the final model. RESULTS: We identified 1511 subjects. 16.9 % were dispensed a medication at discharge. In the adjusted model, several predictors were associated with decreased odds of receiving medications: older age (OR per year older 0.96, 95 % CI 0.95-0.98), black race (OR 0.34, 95 % CI 0.12-0.97), higher comorbidity score (OR 0.89, 95 % CI 0.82 0.96), history of psychosis (OR 0.40, 95 % CI 0.31-0.52), hypertension (OR 0.75, 95 % CI 0.62-0.90), and treatment with steroids in the past year (OR 0.80, 95 % CI 0.70-0.90). Inpatient tobacco control processes were associated with increased odds of receiving medications: documented brief counseling at discharge (OR 3.08, 95 % CI 2.02-4.68) and receipt of smoking cessation medications while inpatient (OR 5.95, 95 % CI 3.19-11.10). CONCLUSIONS: Few patients were treated with tobacco cessation medications at discharge. We found evidence for disparities in treatment, but also potentially beneficial effects of inpatient tobacco control measures. Further focus should be on using novel processes of care to improve provision of medications and decrease the observed disparities. PMID- 26902238 TI - Terry's Nails and Lindsay's Nails: Two Nail Abnormalities in Chronic Systemic Diseases. PMID- 26902240 TI - Capsule Commentary on Alkureishi et al., Impact of Electronic Medical Record Use on the Patient-Doctor Relationship and Communication: A Systematic Review. PMID- 26902239 TI - Rating the Quality of Entrustable Professional Activities: Content Validation and Associations with the Clinical Context. AB - BACKGROUND: Entrustable professional activities (EPAs) have been developed to assess resident physicians with respect to Accreditation Council for Graduate Medical Education (ACGME) competencies and milestones. Although the feasibility of using EPAs has been reported, we are unaware of previous validation studies on EPAs and potential associations between EPA quality scores and characteristics of educational programs. OBJECTIVES: Our aim was to validate an instrument for assessing the quality of EPAs for assessment of internal medicine residents, and to examine associations between EPA quality scores and features of rotations. DESIGN: This was a prospective content validation study to design an instrument to measure the quality of EPAs that were written for assessing internal medicine residents. PARTICIPANTS: Residency leadership at Mayo Clinic, Rochester participated in this study. This included the Program Director, Associate program directors and individual rotation directors. INTERVENTIONS: The authors reviewed salient literature. Items were developed to reflect domains of EPAs useful for assessment. The instrument underwent further testing and refinement. Each participating rotation director created EPAs that they felt would be meaningful to assess learner performance in their area. These 229 EPAs were then assessed with the QUEPA instrument to rate the quality of each EPA. MAIN MEASURES: Performance characteristics of the QUEPA are reported. Quality ratings of EPAs were compared to the primary ACGME competency, inpatient versus outpatient setting and specialty type. KEY RESULTS: QUEPA tool scores demonstrated excellent reliability (ICC range 0.72 to 0.94). Higher ratings were given to inpatient versus outpatient (3.88, 3.66; p = 0.03) focused EPAs. Medical knowledge EPAs scored significantly lower than EPAs assessing other competencies (3.34, 4.00; p < 0.0001). CONCLUSIONS: The QUEPA tool is supported by good validity evidence and may help in rating the quality of EPAs developed by individual programs. Programs should take care when writing EPAs for the outpatient setting or to assess medical knowledge, as these tended to be rated lower. PMID- 26902241 TI - Determinants and Outcomes of Nephrology Care. PMID- 26902243 TI - Air in the Heart: A Reason to Panic? PMID- 26902244 TI - Raeder's Paratrigeminal Syndrome: Headache and Horner's Lacking Anhidrosis. PMID- 26902242 TI - VA and Medicare Utilization Among Dually Enrolled Veterans with Type 2 Diabetes: A Latent Class Analysis. AB - BACKGROUND: Many Veterans treated within the VA Healthcare System (VA) are also enrolled in fee-for-service (FFS) Medicare and receive treatment outside the VA. Prior research has not accounted for the multiple ways that Veterans receive services across healthcare systems. OBJECTIVE: We aimed to establish a typology of VA and Medicare utilization among dually enrolled Veterans with type 2 diabetes. DESIGN: This was a retrospective cohort. PARTICIPANTS: 316,775 community-dwelling Veterans age >= 65 years with type 2 diabetes who were dually enrolled in the VA and FFS Medicare in 2008-2009. METHODS: Using latent class analysis, we identified classes of Veterans based upon their probability of using VA and Medicare diabetes care services, including patient visits, laboratory tests, glucose test strips, and medications. We compared the amount of healthcare use between classes and identified factors associated with class membership using multinomial regression. KEY RESULTS: We identified four distinct latent classes: class 1 (53.9%) had high probabilities of VA use and low probabilities of Medicare use; classes 2 (17.2%), 3 (21.8%), and 4 (7.0%) had high probabilities of VA and Medicare use, but differed in their Medicare services used. For example, Veterans in class 3 received test strips exclusively through Medicare, while Veterans in class 4 were reliant on Medicare for medications. Living >= 40 miles from a VA predicted membership in classes 3 (OR 1.1, CI 1.06-1.15) and 4 (OR 1.11, CI 1.04-1.18), while Medicaid eligibility predicted membership in class 4 (OR 4.30, CI 4.10-4.51). CONCLUSIONS: Veterans with diabetes can be grouped into four distinct classes of dual health system use, representing a novel way to characterize how patients use multiple services across healthcare systems. This classification has applications for identifying patients facing differential risk from care fragmentation. PMID- 26902245 TI - Accuracy of the Safer Dx Instrument to Identify Diagnostic Errors in Primary Care. AB - IMPORTANCE: Diagnostic errors are common and harmful, but difficult to define and measure. Measurement of diagnostic errors often depends on retrospective medical record reviews, frequently resulting in reviewer disagreement. OBJECTIVES: We aimed to test the accuracy of an instrument to help detect presence or absence of diagnostic error through record reviews. DESIGN: We gathered questions from several previously used instruments for diagnostic error measurement, then developed and refined our instrument. We tested the accuracy of the instrument against a sample of patient records (n = 389), with and without previously identified diagnostic errors (n = 129 and n = 260, respectively). RESULTS: The final version of our instrument (titled Safer Dx Instrument) consisted of 11 questions assessing diagnostic processes in the patient-provider encounter and a main outcome question to determine diagnostic error. In comparison with the previous sample, the instrument yielded an overall accuracy of 84 %, sensitivity of 71 %, specificity of 90 %, negative predictive value of 86 %, and positive predictive value of 78 %. All 11 items correlated significantly with the instrument's error outcome question (all p values <= 0.01). Using factor analysis, the 11 questions clustered into two domains with high internal consistency (initial diagnostic assessment, and performance and interpretation of diagnostic tests) and a patient factor domain with low internal consistency (Cronbach's alpha coefficients 0.93, 0.92, and 0.38, respectively). CONCLUSIONS: The Safer Dx Instrument helps quantify the likelihood of diagnostic error in primary care visits, achieving a high degree of accuracy for measuring their presence or absence. This instrument could be useful to identify high-risk cases for further study and quality improvement. PMID- 26902247 TI - Object-based selection is contingent on attentional control settings. AB - The visual system allocates attention in object-based and location-based modes. However, the question of when attention selects objects and when it selects locations remains poorly understood. In this article, we present variations on two classic paradigms from the object-based attention literature, in which object based effects are observed only when the object feature matches the task goal of the observer. In Experiment 1, covert orienting was influenced by task-irrelevant rectangles, but only when the target color matched the rectangle color. In Experiment 2, the region of attentional focus was adjusted to the size of task irrelevant objects, but only when the target color matched the object color. In Experiment 3, we ruled out the possibility that contingent object-based selection is caused by color-based intratrial priming. These demonstrations of contingent object-based attention suggest that object-based selection is neither mandatory nor default, and that object-based effects are contingent on simple, top-down attentional control settings. PMID- 26902246 TI - Combinations of Chronic Conditions, Functional Limitations, and Geriatric Syndromes that Predict Health Outcomes. AB - BACKGROUND: The strategic framework on multiple chronic conditions released by the US Department of Health and Human Services calls for identifying homogeneous subgroups of older adults to effectively target interventions aimed at improving their health. OBJECTIVE: We aimed to identify combinations of chronic conditions, functional limitations, and geriatric syndromes that predict poor health outcomes. DESIGN, SETTING AND PARTICIPANTS Data from the 2010-2012 Health and Retirement Study provided a representative sample of U.S. adults 50 years of age or older (n = 16,640). MAIN MEASURES: Outcomes were: Self-reported fair/poor health, self-rated worse health at 2 years, and 2-year mortality. The main independent variables included self-reported chronic conditions, functional limitations, and geriatric syndromes. We conducted tree-based classification and regression analysis to identify the most salient combinations of variables to predict outcomes. KEY RESULTS: Twenty-nine percent and 23 % of respondents reported fair/poor health and self-rated worse health at 2 years, respectively, and 5 % died in 2 years. The top combinations of conditions identified through our tree analysis for the three different outcome measures (and percent respondents with the outcome) were: a) for fair/poor health status: difficulty walking several blocks, depressive symptoms, and severe pain (> 80 %); b) for self-rated worse health at 2 years: 68.5 years of age or older, difficulty walking several blocks and being in fair/poor health (60 %); and c) for 2-year mortality: 80.5 years of age or older, and presenting with limitations in both ADLs and IADLs (> 40 %). CONCLUSIONS: Rather than chronic conditions, functional limitations and/or geriatric syndromes were the most prominent conditions in predicting health outcomes. These findings imply that accounting for chronic conditions alone may be less informative than also accounting for the co occurrence of functional limitations and geriatric syndromes, as the latter conditions appear to drive health outcomes in older individuals. PMID- 26902248 TI - Differently confident: Susceptibility to bias in perceptual judgments of size interacts with working memory capacity. AB - Much prior research has shown that retrieval of information from long-term memory (LTM) can influence many aspects of complex cognition in situ. However, research also has shown that not all individuals manage information retrieved from LTM in equivalent fashions. Specifically, high working memory capacity (WMC) individuals have been shown to be better able to manage not only what information is retrieved from LTM, but also whether it is applied to the task-at-hand. As such, it is likely that WMC will interact with the biasing influences of prior knowledge on current task performance. In this series of studies, high and low WMC individuals were asked to make perceptual judgments of size that either did or did not activate biasing prior knowledge. Results indicate that when retrieving information from LTM, high WMC individuals are actually more susceptible to perceptual bias and also are erroneously more confident in the accuracy of their response. However, when no retrieval from LTM is necessary, this effect reverses. This suggests that high WMC individuals are indeed able to inhibit such biasing information; however, their overconfidence in the quality of information retrieved from their own LTM can make them susceptible to making errors in perceptual judgments. PMID- 26902249 TI - Categorical information influences conscious perception: An interaction between object-substitution masking and repetition blindness. AB - The visual system is constantly bombarded with dynamic input. In this context, the creation of enduring object representations presents a particular challenge. We used object-substitution masking (OSM) as a tool to probe these processes. In particular, we examined the effect of target-like stimulus repetitions on OSM. In visual crowding, the presentation of a physically identical stimulus to the target reduces crowding and improves target perception, whereas in spatial repetition blindness, the presentation of a stimulus that belongs to the same category (type) as the target impairs perception. Across two experiments, we found an interaction between spatial repetition blindness and OSM, such that repeating a same-type stimulus as the target increased masking magnitude relative to presentation of a different-type stimulus. These results are discussed in the context of the formation of object files. Moreover, the fact that the inducer only had to belong to the same "type" as the target in order to exacerbate masking, without necessarily being physically identical to the target, has important implications for our understanding of OSM per se. That is, our results show the target is processed to a categorical level in OSM despite effective masking and, strikingly, demonstrate that this category-level content directly influences whether or not the target is perceived, not just performance on another task (as in priming). PMID- 26902250 TI - Effect of Osmolytes and Guanidinium Chloride on the Enzymatic Properties of Bovine alpha-Chymotrypsin. AB - We have studied the effect of guanidinium chloride (Gdn.Cl) and different osmolytes such as betaine, trimethylamine-N-oxide (TMAO) and urea on the rate of chymotrypsin catalyzed reaction. The rates were measured using three synthetic chromogenic substrates, succinyl-ala-ala-pro-arg-pNA (AAPR), succinyl-ala-ala-pro leu-pNA (AAPL), and succinyl-ala-ala-pro-phe-pNA (AAPF). Qualitatively, the results with the three substrates were identical. Guanidinium chloride and urea produced a linear decrease while TMAO produced a linear increase in the rate with increase in osmolyte concentration. Betaine had practically no effect on the rate of enzyme catalyzed reaction up to a concentration of 1.2 M. However, quantitatively the rate change per molar concentration of osmolyte (or Gdn.Cl) was significantly larger for AAPR that has a polar and cationic reactive site residue than the two substrates (AAPL and AAPF) that have non-polar reactive site residues. These results suggest that the chemical nature of the substrate (and presumably the active site of the enzyme) plays an important role in determining the effect of osmolytes in enzyme catalyzed reactions. PMID- 26902251 TI - Mechanism of Lipid Binding of Human Apolipoprotein E3 by Hydrogen/Deuterium Exchange/Mass Spectrometry and Fluorescence Polarization. AB - BACKGROUND: Human apolipoprotein E3 (apoE3) is an exchangeable apolipoprotein that plays a critical role in maintaining plasma cholesterol/triglyceride homeostasis. The C-terminal (CT) domain of apoE3 (residues 201-299) is composed of amphipathic alpha-helices C1: W210-S223, C2: V236-E266, and C3: D271-W276, which play a dominant role in mediating high-affinity lipid binding. OBJECTIVE: The objective is to understand the accessibility of the CT domain at the sub domain level and the mechanistic details regarding lipid-binding interaction. METHODS: Hydrogen-deuterium exchange coupled to mass spectrometry (HDX/MS) of recombinant wild type (WT) apoE(201-299), chemical-induced unfolding monitored as changes in fluorescence polarization (FP) of labeled apoE(201-299) bearing a probe at specified sites, and lipid binding studies were carried out. RESULTS: HDX/MS revealed that residues towards the C-terminal end of the domain display significantly lower %D uptake compared to those towards the center, suggesting extensive protein-protein interaction in this segment. Functional assays showed that locking apoE(201-299) in an inter-molecular disulfide-bonded state at position 209, 223, 255, or 277 significantly decreases its ability to interact with lipids, especially when tethered towards the ends; this could be restored by reduction. Unfolding studies indicate that the C-terminal end offers less resistance to unfolding compared to the central portion of the domain. CONCLUSION: Taken together, our data suggest that two dimers of CT domain are juxtaposed around helix C3 leading to apoE3 tetramerization, and that dissociation to monomeric units is a required step in lipid binding, with helix C3 likely seeking stability via lipid interaction prior to helices C1 or C2. PMID- 26902252 TI - First Presentation of Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome in Pregnancy. AB - BACKGROUND: Reed's syndrome, also known as hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome, is an autosomal dominant condition in which affected individuals may develop cutaneous leiomyomas, uterine fibroids, and renal cell carcinoma. OBJECTIVE: This report describes a unique case of HLRCC because it presented in pregnancy with development of cutaneous pilar leiomyomas. METHODS: Review of the literature for previous cases of Reed's syndrome during pregnancy including PubMed and Medline search. RESULTS: Genetic testing of this patient demonstrated a mutation in the fumarate hydratase (FH) gene. Review of the literature showed only 1 previous case series that described the onset of cutaneous lesions during pregnancy. CONCLUSION: This case serves as a reminder that there may exist a correlation between pregnancy and the first manifestation of cutaneous lesions in patients with HLRCC, and thus an increased clinical suspicion is warranted during this period. PMID- 26902254 TI - International recommendations for national patient safety incident reporting systems: an expert Delphi consensus-building process. AB - BACKGROUND: Patient safety incident reporting systems (PSRS) have been established for over a decade, but uncertainty remains regarding the role that they can and ought to play in quantifying healthcare-related harm and improving care. OBJECTIVE: To establish international, expert consensus on the purpose of PSRS regarding monitoring and learning from incidents and developing recommendations for their future role. METHODS: After a scoping review of the literature, semi-structured interviews with experts in PSRS were conducted. Based on these findings, a survey-based questionnaire was developed and subsequently completed by a larger expert panel. Using a Delphi approach, consensus was reached regarding the ideal role of PSRSs. Recommendations for best practice were devised. RESULTS: Forty recommendations emerged from the Delphi procedure on the role and use of PSRS. Experts agreed reporting system should not be used as an epidemiological tool to monitor the rate of harm over time or to appraise the relative safety of hospitals. They agreed reporting is a valuable mechanism for identifying organisational safety needs. The benefit of a national system was clear with respect to medication error, device failures, hospital-acquired infections and never events as these problems often require solutions at a national level. Experts recommended training for senior healthcare professionals in incident investigation. Consensus recommendation was for hospitals to take responsibility for creating safety solutions locally that could be shared nationally. CONCLUSIONS: We obtained reasonable consensus among experts on aims and specifications of PSRS. This information can be used to reflect on existing and future PSRS, and their role within the wider patient safety landscape. The role of PSRS as instruments for learning needs to be elaborated and developed further internationally. PMID- 26902255 TI - Multidrug Resistance Acinetobacter Bacteremia Secondary to Ventilator-Associated Pneumonia: Risk Factors and Outcome. AB - PURPOSE: Acinetobacter baumannii is a multidrug resistant (MDR), gram-negative bacterium commonly implicated in ventilator-associated pneumonia (VAP) in critically ill patients. Patients in the intensive care unit (ICU) with VAP often subsequently develop A baumannii bacteremia, which may significantly worsen outcomes. MATERIALS AND METHODS: In this study, we retrospectively reviewed the clinical and laboratory records of 129 ICU patients spanning 6 years with MDR A baumannii VAP; 46 (35%) of these patients had concomitant MDR A baumannii bacteremia. RESULTS: The ICU mortality rate was higher in patients with VAP having A baumannii bacteremia compared to nonbacteremic patients (32.4% vs 9.6% respectively, P < .005). Age >65 years, an Acute Physiology and Chronic Health Evaluation II (APACHE-II) score higher than 20, a Sequential Organ Failure Assessment (SOFA) score higher than 7 on the day of bacteremia, and the presence of comorbid disease (chronic obstructive pulmonary disease [COPD] and chronic renal failure) were found to be independent risk factors for in-hospital mortality in this population. Multidrug resistant A baumannii was not an independent risk factor for mortality. CONCLUSION: Although the presence of comorbid diseases (COPD and chronic renal failure) and severity of disease (APACHE > 20 and SOFA >7) were found to be independent risk factors for ICU mortality, MDR A baumannii bacteremia was not an independent risk factor for mortality in our critically ill population. PMID- 26902256 TI - NHS in England embraces collaboration in tackling biggest crisis in its history. PMID- 26902257 TI - The effects of social identity threat and social identity affirmation on laypersons' perception of scientists. AB - Public debates about socio-scientific issues (e.g. climate change or violent video games) are often accompanied by attacks on the reputation of the involved scientists. Drawing on the social identity approach, we report a minimal group experiment investigating the conditions under which scientists are perceived as non-prototypical, non-reputable, and incompetent. Results show that in-group affirming and threatening scientific findings (compared to a control condition) both alter laypersons' evaluations of the study: in-group affirming findings lead to more positive and in-group threatening findings to more negative evaluations. However, only in-group threatening findings alter laypersons' perceptions of the scientists who published the study: scientists were perceived as less prototypical, less reputable, and less competent when their research results imply a threat to participants' social identity compared to a non-threat condition. Our findings add to the literature on science reception research and have implications for understanding the public engagement with science. PMID- 26902258 TI - One-step Conjugation of Glycyrrhetinic Acid to Cationic Polymers for High performance Gene Delivery to Cultured Liver Cell. AB - Gene therapies represent a promising therapeutic route for liver cancers, but major challenges remain in the design of safe and efficient gene-targeting delivery systems. For example, cationic polymers show good transfection efficiency as gene carriers, but are hindered by cytotoxicity and non-specific targeting. Here we report a versatile method of one-step conjugation of glycyrrhetinic acid (GA) to reduce cytotoxicity and improve the cultured liver cell -targeting capability of cationic polymers. We have explored a series of cationic polymer derivatives by coupling different ratios of GA to polypropylenimine (PPI) dendrimer. These new gene carriers (GA-PPI dendrimer) were systematically characterized by UV-vis,(1)H NMR titration, electron microscopy, zeta potential, dynamic light-scattering, gel electrophoresis, confocal microscopy and flow cytometry. We demonstrate that GA-PPI dendrimers can efficiently load and protect pDNA, via formation of nanostructured GA-PPI/pDNA polyplexes. With optimal GA substitution degree (6.31%), GA-PPI dendrimers deliver higher liver cell transfection efficiency (43.5% vs 22.3%) and lower cytotoxicity (94.3% vs 62.5%, cell viability) than the commercial bench-mark DNA carrier bPEI (25 kDa) with cultured liver model cells (HepG2). There results suggest that our new GA-PPI dendrimer are a promising candidate gene carrier for targeted liver cancer therapy. PMID- 26902259 TI - Population structure and acquisition of the vanB resistance determinant in German clinical isolates of Enterococcus faecium ST192. AB - In the context of the global action plan to reduce the dissemination of antibiotic resistances it is of utmost importance to understand the population structure of resistant endemic bacterial lineages and to elucidate how bacteria acquire certain resistance determinants. Vancomycin resistant enterococci represent one such example of a prominent nosocomial pathogen on which nation wide population analyses on prevalent lineages are scarce and data on how the bacteria acquire resistance, especially of the vanB genotype, are still under debate. With respect to Germany, an increased prevalence of VRE was noted in recent years. Here, invasive infections caused by sequence type ST192 VRE are often associated with the vanB-type resistance determinant. Hence, we analyzed 49 vanB-positive and vanB-negative E. faecium isolates by means of whole genome sequencing. Our studies revealed a distinct population structure and that spread of the Tn1549-vanB-type resistance involves exchange of large chromosomal fragments between vanB-positive and vanB-negative enterococci rather than independent acquisition events. In vitro filter-mating experiments support the hypothesis and suggest the presence of certain target sequences as a limiting factor for dissemination of the vanB element. Thus, the present study provides a better understanding of how enterococci emerge into successful multidrug resistant nosocomial pathogens. PMID- 26902260 TI - Facile One-pot Transformation of Iron Oxides from Fe2O3 Nanoparticles to Nanostructured Fe3O4@C Core-Shell Composites via Combustion Waves. AB - The development of a low-cost, fast, and large-scale process for the synthesis and manipulation of nanostructured metal oxides is essential for incorporating materials with diverse practical applications. Herein, we present a facile one pot synthesis method using combustion waves that simultaneously achieves fast reduction and direct formation of carbon coating layers on metal oxide nanostructures. Hybrid composites of Fe2O3 nanoparticles and nitrocellulose on the cm scale were fabricated by a wet impregnation process. We demonstrated that self-propagating combustion waves along interfacial boundaries between the surface of the metal oxide and the chemical fuels enabled the release of oxygen from Fe2O3. This accelerated reaction directly transformed Fe2O3 into Fe3O4 nanostructures. The distinctive color change from reddish-brown Fe2O3 to dark gray Fe3O4 confirmed the transition of oxidation states and the change in the fundamental properties of the material. Furthermore, it simultaneously formed carbon layers of 5-20 nm thickness coating the surfaces of the resulting Fe3O4 nanoparticles, which may aid in maintaining the nanostructures and improving the conductivity of the composites. This newly developed use of combustion waves in hybridized nanostructures may permit the precise manipulation of the chemical compositions of other metal oxide nanostructures, as well as the formation of organic/inorganic hybrid nanostructures. PMID- 26902261 TI - Protective effects of fenofibrate against acute lung injury induced by intestinal ischemia/reperfusion in mice. AB - This experiment was conducted to evaluate whether pretreatment with fenofibrate could mitigate acute lung injury (ALI) in a mice model of intestinal ischemia/reperfusion (I/R). Male C57BL/6 mice were randomly assigned into three groups (n = 6): sham, intestinal I/R + vehicle, and intestinal I/R + fenofibrate. Intestinal I/R was achieved by clamping the superior mesenteric artery. Fenofibrate (100 mg/kg) or equal volume of vehicle was injected intraperitoneally 60 minutes before the ischemia. At the end of experiment, measurement of pathohistological score, inflammatory mediators and other markers were performed. In addition, a 24-hour survival experiment was conducted in intestinal I/R mice treated with fenofibrate or vehicle. The chief results were as anticipated. Pathohistological evaluation indicated that fenofibrate ameliorated the local intestine damage and distant lung injury. Pretreatment with fenofibrate significantly decreased inflammatory factors in both the intestine and the lung. Consistently, renal creatine levels and hepatic ALT levels were significantly decreased in the fenofibrate group. Moreover, serum systemic inflammatory response indicators were significantly alleviated in the fenofibrate group. In addition, fenofibrate administration significantly improved the survival rate. Collectively, our data indicated that pretreatment with fenofibrate prior to ischemia attenuated intestinal I/R injury and ALI. PMID- 26902262 TI - Regulating retrotransposon activity through the use of alternative transcription start sites. AB - Retrotransposons, the ancestors of retroviruses, have the potential for gene disruption and genomic takeover if not kept in check. Paradoxically, although host cells repress these elements by multiple mechanisms, they are transcribed and are even activated under stress conditions. Here, we describe a new mechanism of retrotransposon regulation through transcription start site (TSS) selection by altered nucleosome occupancy. We show that Fun30 chromatin remodelers cooperate to maintain a high level of nucleosome occupancy at retrotransposon-flanking long terminal repeat (LTR) elements. This enforces the use of a downstream TSS and the production of a truncated RNA incapable of reverse transcription and retrotransposition. However, in stressed cells, nucleosome occupancy at LTR elements is reduced, and the TSS shifts to allow for productive transcription. We propose that controlled retrotransposon transcription from a nonproductive TSS allows for rapid stress-induced activation, while preventing uncontrolled transposon activity in the genome. PMID- 26902264 TI - Macroscopic tensile plasticity by scalarizating stress distribution in bulk metallic glass. AB - The macroscopic tensile plasticity of bulk metallic glasses (BMGs) is highly desirable for various engineering applications. However, upon yielding, plastic deformation of BMGs is highly localized into narrow shear bands and then leads to the "work softening" behaviors and subsequently catastrophic fracture, which is the major obstacle for their structural applications. Here we report that macroscopic tensile plasticity in BMG can be obtained by designing surface pore distribution using laser surface texturing. The surface pore array by design creates a complex stress field compared to the uniaxial tensile stress field of conventional glassy specimens, and the stress field scalarization induces the unusual tensile plasticity. By systematically analyzing fracture behaviors and finite element simulation, we show that the stress field scalarization can resist the main shear band propagation and promote the formation of larger plastic zones near the pores, which undertake the homogeneous tensile plasticity. These results might give enlightenment for understanding the deformation mechanism and for further improvement of the mechanical performance of metallic glasses. PMID- 26902263 TI - Differences on photosynthetic limitations between leaf margins and leaf centers under potassium deficiency for Brassica napus L. AB - Analyzing the proportions of stomatal (SL), mesophyll conductance (MCL) and biochemical limitations (BL) imposed by potassium (K) deficit, and evaluating their relationships to leaf K status will be helpful to understand the mechanism underlying the inhibition of K deficiency on photosynthesis (A). A quantitative limitation analysis of K deficiency on photosynthesis was performed on leaf margins and centers under K deficiency and sufficient K supply treatments of Brassica napus L. Potassium deficiency decreased A, stomatal (gs) and mesophyll conductance (gm) of margins, SL, MCL and BL accounted for 23.9%, 33.0% and 43.1% of the total limitations. While for leaf centers, relatively low limitations occurred. Nonlinear curve fitting analysis indicated that each limiting factor generated at same leaf K status (1.07%). Although MCL was the main component of limitations when A began to fall, BL replaced it at a leaf K concentration below 0.78%. Up-regulated MCL was related to lower surface area of chloroplasts exposed to intercellular airspaces (Sc/S) and larger cytosol diffusion resistance but not the cell wall thickness. Our results highlighted that photosynthetic limitations appear simultaneously under K deficiency and vary with increasing K deficiency intensity. PMID- 26902265 TI - Neurotensin-induced miR-133alpha expression regulates neurotensin receptor 1 recycling through its downstream target aftiphilin. AB - Neurotensin (NT) triggers signaling in human colonic epithelial cells by activating the G protein-coupled receptor, the neurotensin receptor 1 (NTR1). Activated NTR1 traffics from the plasma membrane to early endosomes, and then recycles. Although sustained NT/NTR1 signaling requires efficient NTR1 recycling, little is known about the regulation of NTR1 recycling. We recently showed that NT/NTR1 signaling increases expression of miR-133alpha. Herein, we studied the mechanism of NT-regulated miR-133alpha expression and examined the role of miR 133alpha in intracellular NTR1 trafficking in human NCM460 colonocytes. We found that NT-induced miR-133alpha upregulation involves the negative transcription regulator, zinc finger E-box binding homeobox 1. Silencing of miR-133alpha or overexpression of aftiphilin (AFTPH), a binding target of miR-133alpha, attenuated NTR1 trafficking to plasma membrane in human colonocytes, without affecting NTR1 internalization. We localized AFTPH to early endosomes and the trans-Golgi network (TGN) in unstimulated human colonic epithelial cells. AFTPH overexpression reduced NTR1 localization in early endosomes and increased expression of proteins related to endosomes and the TGN trafficking pathway. AFTPH overexpression and de-acidification of intracellular vesicles increased NTR1 expression. Our results suggest a novel mechanism of GPCR trafficking in human colonic epithelial cells by which a microRNA, miR-133alpha regulates NTR1 trafficking through its downstream target AFTPH. PMID- 26902266 TI - Genome wide association study of uric acid in Indian population and interaction of identified variants with Type 2 diabetes. AB - Abnormal level of Serum Uric Acid (SUA) is an important marker and risk factor for complex diseases including Type 2 Diabetes. Since genetic determinant of uric acid in Indians is totally unexplored, we tried to identify common variants associated with SUA in Indians using Genome Wide Association Study (GWAS). Association of five known variants in SLC2A9 and SLC22A11 genes with SUA level in 4,834 normoglycemics (1,109 in discovery and 3,725 in validation phase) was revealed with different effect size in Indians compared to other major ethnic population of the world. Combined analysis of 1,077 T2DM subjects (772 in discovery and 305 in validation phase) and normoglycemics revealed additional GWAS signal in ABCG2 gene. Differences in effect sizes of ABCG2 and SLC2A9 gene variants were observed between normoglycemics and T2DM patients. We identified two novel variants near long non-coding RNA genes AL356739.1 and AC064865.1 with nearly genome wide significance level. Meta-analysis and in silico replication in 11,745 individuals from AUSTWIN consortium improved association for rs12206002 in AL356739.1 gene to sub-genome wide association level. Our results extends association of SLC2A9, SLC22A11 and ABCG2 genes with SUA level in Indians and enrich the assemblages of evidence for SUA level and T2DM interrelationship. PMID- 26902267 TI - An interactive web-based application for Comprehensive Analysis of RNAi-screen Data. AB - RNAi screens are widely used in functional genomics. Although the screen data can be susceptible to a number of experimental biases, many of these can be corrected by computational analysis. For this purpose, here we have developed a web-based platform for integrated analysis and visualization of RNAi screen data named CARD (for Comprehensive Analysis of RNAi Data; available at https://card.niaid.nih.gov). CARD allows the user to seamlessly carry out sequential steps in a rigorous data analysis workflow, including normalization, off-target analysis, integration of gene expression data, optimal thresholds for hit selection and network/pathway analysis. To evaluate the utility of CARD, we describe analysis of three genome-scale siRNA screens and demonstrate: (i) a significant increase both in selection of subsequently validated hits and in rejection of false positives, (ii) an increased overlap of hits from independent screens of the same biology and (iii) insight to microRNA (miRNA) activity based on siRNA seed enrichment. PMID- 26902268 TI - Corrigendum: Identification of novel PKD1 and PKD2 mutations in a Chinese population with autosomal dominant polycystic kidney disease. PMID- 26902270 TI - [Clinical significance of immunologic monitoring in septic patients]. AB - Sepsis induced by burns, trauma, and surgical stress, remains a major cause of death of patients in ICUs. A growing number of evidence shows that sepsis may result in dysfunction of innate and adaptive immune system, including the abnormal disorder of immune response of T lymphocytes, regulatory T lymphocytes, and dendritic cells, resulting in a state of immune depression. It is of great significance that dynamic monitoring of immune function and the related indicators might help to assess the risk of secondary infection, the prognosis of septic patients, and to guide the treatment of severe sepsis. PMID- 26902271 TI - [Prevention and treatment strategy for burn wound sepsis in children]. AB - Wound sepsis is one of the main causes of death in patients with severe burn and trauma. The high incidence of burn wound sepsis in children is attributed to their imperfect immune system function, poor resistance against infection, and the weakened skin barrier function after burn. The key to reduce the mortality of pediatric patients with burn wound sepsis is to enhance the understanding of its etiology, epidemiology, pathogenesis, and diagnostic criteria, in order to improve its early diagnosis and treatment. PMID- 26902269 TI - Genomic and phenotypic characterization of the species Acinetobacter venetianus. AB - Crude oil is a complex mixture of hydrocarbons and other organic compounds that can produce serious environmental problems and whose removal is highly demanding in terms of human and technological resources. The potential use of microbes as bioremediation agents is one of the most promising fields in this area. Members of the species Acinetobacter venetianus have been previously characterized for their capability to degrade n-alkanes and thus may represent interesting model systems to implement this process. Although a preliminary experimental characterization of the overall hydrocarbon degradation capability has been performed for five of them, to date, the genetic/genomic features underlying such molecular processes have not been identified. Here we have integrated genomic and phenotypic information for six A. venetianus strains, i.e. VE-C3, RAG-1(T), LUH 13518, LUH 7437, LUH 5627 and LUH 8758. Besides providing a thorough description of the A. venetianus species, these data were exploited to infer the genetic features (presence/absence patterns of genes) and the short-term evolutionary events possibly responsible for the variability in n-alkane degradation efficiency of these strains, including the mechanisms of interaction with the fuel droplet and the subsequent catabolism of this pollutant. PMID- 26902272 TI - [Emphasize the diagnosis and treatment of infective endocarditis in patients with severe burn]. AB - The incidence and mortality of infective endocarditis (IE) in patients with severe burn remain high, which are attributed to invasive procedures, bacteremia, and wound infection after burns. Clinical clues for IE in burns are usually masked by burn-related manifestations, so the diagnosis of IE may be delayed or missed. For burned patients with persistent bacteremia of unknown source, especially Staphylococcus aureus-induced bacteremia, the diagnosis of IE should be considered according to the Duke criteria, and early echocardiography performance is particularly important. Antibiotic therapy is the mainstay initial management, and early surgical intervention is strongly recommended once IE is clearly diagnosed in patients with burns. In order to lower the incidence and mortality of IE in burns, it is very important to take prophylactic procedures along with the whole course of burn management. PMID- 26902273 TI - [Prognostic significance of plasma gelsolin in severe burn patients with sepsis]. AB - OBJECTIVE: To investigate the changes in plasma gelsolin (pGSN) levels in severe burn patients with sepsis, and to evaluate the prognosis of patients when combined with other related clinical indexes. METHODS: Sixty-five severe burn patients with sepsis hospitalized from June 2013 to June 2015 conforming to the study criteria were divided into death group (n=24) and survival group (n=41) according to the clinical outcome on post sepsis diagnosis day (PSD) 28. The pGSN levels of patients were determined on PSD 1, 3, 7, and 14 with double antibody sandwich enzyme-linked immunosorbent assay. The serum level of C-reactive protein (CRP), serum level of procalcitonin, lactate level of arterial blood, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and Sequential Organ Failure Assessment (SOFA) score were determined or recorded on PSD 1. Data were processed with repeated measurement analysis of variance, t test, and chi-square test. On PSD 1, the pGSN level, serum level of CRP, serum level of procalcitonin, lactate level of arterial blood, APACHE II score, and SOFA score of 65 patients were collected to screen the independent risk factors related to death with single factor and multi-factor Logistic regression analysis. Receiver operating characteristic (ROC) curves of the independent risk factors related to death were plotted to evaluate the predictive power for death in 65 patients. RESULTS: (1) The pGSN levels of patients in death group on PSD 1, 3, 7, and 14 were respectively (146+/-44), (85+/-24), (28+/-7), and (19+/-4) mg/L, obviously lower than those in survival group [(287+/-82), (179+/-51), (196+/-56), and (249+/-67) mg/L, with t values from 1.735 to 4.304, P<0.05 or P<0.01]. (2) The serum level of CRP, serum level of procalcitonin, lactate level of arterial blood, APACHE II score, and SOFA score of patients in death group on PSD 1 were respectively (56+/ 7) mg/L, (12.54+/-0.82) MUg/L, (2.74+/-0.27) mmol/L, (24.3+/-2.4) points, and (11.43+/-0.57) points, significantly higher than those in survival group [(35+/ 4) mg/L, (2.38+/-0.16) MUg/L, (1.83+/-0.12) mmol/L, (15.0+/-1.5) points, and (7.22+/-0.23) points, with t values from 1.902 to 3.883, P<0.05 or P<0.01]. (3) Multi-factor Logistic regression analysis showed that the pGSN level (odds ratio: 6.83, 95% confidence interval: 4.33-10.25, P<0.01) and APACHE II score (odds ratio: 5.27, 95% confidence interval: 2.28-9.16, P<0.01) were the independent risk factors related to death in 65 patients on PSD 1. (4) The total areas under the ROC curves of pGSN level and APACHE II score for predicting death of 65 patients on PSD 1 were respectively 0.89 and 0.86, and 142 mg/L and 21 points were respectively chosen as the optimal threshold values, with sensitivity of 87% and 83% and specificity of 86% and 89%. CONCLUSIONS: For severe burn patients with sepsis, lowering of pGSN level and elevation of APACHE II score are obviously correlated with increase in case fatality rates. Monitoring the dynamic changes in pGSN level and APACHE II score during the early stage may be useful to predict the prognosis of severe burn patients with sepsis. PMID- 26902274 TI - [Effects of exogenous carbon monoxide-releasing molecule 2 intervention in vitro on formation of human neutrophil extracellular traps stimulated by endotoxin/lipopolysaccharide and its mechanism]. AB - OBJECTIVE: To explore the effects of exogenous carbon monoxide-releasing molecule 2 (CORM-2) on formation of human neutrophil extracellular traps (NETs) stimulated by endotoxin/lipopolysaccharide (LPS) and its relevant mechanism. METHODS: Venous blood samples were collected from a healthy adult volunteer to isolate neutrophils. The neutrophils were divided into normal control (NC) group, LPS group, LPS+ 10 MUmol/L CORM-2 group, LPS+ 50 MUmol/L CORM-2 group, and LPS+ inactive CORM-2 (iCORM-2) group according to the random number table. No treatment was given to the neutrophils in NC group. The neutrophils in LPS group underwent LPS stimulation (1 MUL, 1 MUg/mL). The neutrophils in LPS+ 10 MUmol/L CORM-2 group, LPS+ 50 MUmol/L CORM-2 group, and LPS+ iCORM-2 group underwent the same LPS stimulation as that in LPS group and treatment of 10 MUmol/L CORM-2, 50 MUmol/L CORM-2, and 50 MUmol/L iCORM-2, respectively, with the volune of 1 MUL. After conventional culture for 1 h, the number of NETs was determined with propidium iodide staining method; the early cell apoptosis rate was determined with flow cytometer; the generation level of reactive oxygen species (ROS) was assessed with dihydrogenrhodamine 123 fluorescent probe staining method (denoted as mean fluorescence intensity); the expression level of phosphorylated extracellular regulated kinase 1/2 (p-ERK1/2) was determined by Western blotting. The sample numbers of each group in the 4 experiments were all 5. Data were processed with one-way analysis of variance and SNK test. RESULTS: (1) The numbers of NETs per 400-time visual field in cells of LPS and LPS+ iCORM-2 groups were close to the number in NC group (with P values above 0.05). The number of NETs per 400-time visual field was significantly larger in cells of LPS+ 10 MUmol/L CORM-2 and LPS+ 50 MUmol/L CORM-2 groups than in NC and LPS groups (with P values below 0.05). The number of NETs per 400-time visual field in cells of LPS+ iCORM-2 group was close to that of LPS group (P>0.05). (2) The early cell apoptosis rate was significantly increased in LPS, LPS+ 10 MUmol/L CORM-2, LPS+ 50 MUmol/L CORM-2, and LPS+ iCORM-2 groups than in NC group (with P values below 0.05). The early cell apoptosis rates in LPS+ 10 MUmol/L CORM-2, LPS+ 50 MUmol/L CORM-2, and LPS+ iCORM-2 groups were close to the rate in LPS group (with P values above 0.05). (3) The generation level of ROS was significantly higher in cells of LPS, LPS+ 10 MUmol/L CORM-2, and LPS+ iCORM-2 groups than in NC group (with P values below 0.05). The generation level of ROS in cells of LPS+ 50 MUmol/L CORM-2 group was close to that of NC group (P>0.05). The generation level of ROS was lower in cells of LPS+ 10 MUmol/L CORM-2 and LPS+ 50 MUmol/L CORM-2 groups than in LPS group (with P values below 0.05), while the generation level of ROS in cells of LPS+ iCORM-2 group was close to that of LPS group (P>0.05). (4) The expression levels of p-ERK1/2 in cells of LPS and LPS+ iCORM-2 groups (respectively 0.0311+/-0.001 and 0.0309+/-0.0018) were close to the level in NC group (0.0304+/-0.0046, with P values above 0.05). The expression level of p ERK1/2 was significantly higher in cells of LPS+ 10 MUmol/L CORM-2 and LPS+ 50 MUmol/L CORM-2 groups (respectively 0.7891+/-0.0201 and 1.2970+/-0.0056) than in NC group (with P values below 0.05). The expression level of p-ERK1/2 was significantly higher in cells of LPS+ 10 MUmol/L CORM-2 and LPS+ 50 MUmol/L CORM 2 groups than in LPS group (with P values below 0.05). The expression level of p ERK1/2 in cells of LPS+ iCORM-2 group was close to that of LPS group (P>0.05). CONCLUSIONS: CORM-2 can obviously increase the production of NETs in LPS-induced neutrophils, and it might be attributable to the promotion of inhibition of ROS generation and phosphorylation of ERK1/2. PMID- 26902275 TI - [Changes in the expression of three markers in T lymphocytes of peripheral blood and immunoregulatory mechanisms of burned mice with sepsis at early stage]. AB - OBJECTIVE: To study the expression levels of annexin A1 (ANXA1), GATA-3, and T bet in T lymphocytes of peripheral blood in burned mice with sepsis at early stage, and to analyze their immune regulatory mechanisms. METHODS: Seven-hundred and eighty male mice of clean grade were divided into sham injury group (n=60, sham injured on the back by immersing in 37 C warm water for 10 s), burn group (n=240, inflicted with 20% TBSA deep partial- thickness burn on the back by immersing in 100 C hot water for 10 s), sepsis group (n=240, intraperitoneally injected with 6 mg/kg lipopolysaccharide), and burn+ sepsis group (n=240) according to the random number table. Mice of burn+ sepsis group were treated as that in burn group at first, and then they were treated as that in sepsis group. (1) Immediately after injury, six mice in sham injury group were selected to collect lymphocyte suspension of peripheral blood (1 tube each mouse) according to the random number table. According to the random number table, 6 mice of each of the other three groups were respectively selected at post injury hour (PIH) 12, 24, 48, and 72 for the collection of lymphocyte suspension from peripheral blood (1 tube each mouse). Each tube of cell suspension was equally divided into two parts. Fluorescein isothiocyanate (FITC)-labeled human anti-mouse CD4 monoclonal antibody and phycoerythrin (PE)-labeled human anti-mouse interferon gamma monoclonal antibody were added to one part of cell suspension to mark helper T lymphocyte 1 (Th1). FITC-labeled human anti-mouse CD4 monoclonal antibody and PE-labeled human anti-mouse interleukin-4 (IL-4) monoclonal antibody were added to the other part of cell suspension to mark Th2. The percentages of Th1 and Th2 were determined with flow cytometer, and the ratio of Th1 to Th2 was calculated. (2) According to the random number table, 18 mice in sham injury group were selected immediately after injury for the collection of lymphocyte suspension of peripheral blood (1 tube each mouse), and 18 mice of each of the other 3 groups were respectively selected at PIH 12, 24, 48, and 72 to collect the lymphocyte suspension of peripheral blood (1 tube each mouse). The mRNA expression levels of ANXA1, GATA-3, and T-bet were determined by real-time fluorescent quantitative reverse transcription-PCR. (3) Immediately after injury, 36 mice in sham injury group were selected to collect lymphocyte suspension of peripheral blood (1 tube each mouse) according to the random number table, and then 36 tubes of cell suspension were divided into 6 batches (6 tubes each batch). Each one of 6 kinds of antibody combinations: antibodies for labeling Th1 and Th2 in combination with PE-anthocyanin 7 labeled human anti-mouse ANXA1 monoclonal antibody, PE-anthocyanin 7 labeled human anti-mouse GATA-3 monoclonal antibody, and PE-anthocyanin 7 labeled human anti-mouse T-bet monoclonal antibody was added to 1 tube of cell suspension at each batch. According to the random number table, 36 mice of each of the other 3 groups were respectively selected at PIH 12, 24, 48, and 72 for the collection of lymphocyte suspension of peripheral blood (1 tube each mouse), and then 36 tubes of cell suspension at each time point were divided into 6 batches for marking with 3 kinds of surface markers of Th1 and Th2 (6 tubes each batch). Each one of above-mentioned 6 kinds of antibodies was added to 1 tube of cell suspension at each time point for each batch. The percentages of ANXA1, GATA-3, and T-bet positive cells in Th1 and Th2 were determined with flow cytometer. Data were processed with one-way analysis of variance, analysis of variance of factorial design, and SNK test. The relationship between the percentages of ANXA1 positive cell and the percentages of GATA-3 positive cell in Th1 and Th2, and mRNA expression level of ANXA1 and mRNA expression level of GATA-3 in lymphocytes were assessed by linear correlation analysis. RESULTS: (1) Compared with those in sham injury group immediately after injury, the percentages of Th1 and Th2 and the ratio of Th1 to Th2 of mice in burn group were significantly decreased from PIH 24 on, with P values below 0.05; the percentages of Th1 and Th2 and the ratios of Th1 to Th2 of mice in sepsis group and burn+ sepsis group were significantly decreased from PIH 12 on, with P values below 0.05. (2) Compared with those in sham injury group immediately after injury, the mRNA expression levels of ANXA1 and GATA-3 in lymphocyte of mice in burn group were significantly decreased from PIH 24 on, with P values below 0.05; the mRNA expression level of T-bet was significantly decreased at PIH 24 but significantly increased at PIH 48 and 72, with P values below 0.05. Compared with those in sham injury group immediately after injury, the mRNA expression levels of ANXA1 and GATA-3 in lymphocytes of mice in sepsis group were significantly decreased from PIH 12 on, and the mRNA expression level of T-bet was increased significantly from PIH 12 on, with P values below 0.05; the mRNA expression levels of ANXA1, GATA-3, and T-bet in lymphocytes of mice in burn+ sepsis group were significantly decreased from PIH 12 on, with P values below 0.05, reaching the nadir at PIH 72 (0.50+/-0.04, 0.45+/-0.03, 0.21+/-0.05, respectively). (3) A significant positive correlation was observed between ANXA1 mRNA expression level and GATA-3 mRNA expression level in lymphocytes of peripheral blood (r=0.862, P<0.05). (4) Compared with those in sham injury group immediately after injury, the percentages of ANXA1 and GATA-3 positive cellsin Th1 and Th2 of mice in burn group were significantly lowered from PIH 24 on, and the percentage of T-bet positive cells was significantly decreased at PIH 24, but it was increased from PIH 48 on, with P values below 0.05. The percentages of ANXA1 and GATA-3 positive cells in Th1 and Th2 of mice in sepsis group were continuously decreased from PIH 12 on, which were lower at most time points than those in sham injury group immediately after injury, with P values below 0.05. The percentages of T-bet positive cells in Th1 and Th2 of mice in sepsis group were significantly increased since PIH 12 as compared with those in sham injury group immediately after injury, with P values below 0.05. The percentages of ANXA1, GATA-3, and T-bet positive cells in Th1 and Th2 of mice in burn+ sepsis group were continuously lowered from PIH 12, with significantly statistical differences at most time points as compared with those in sham injury group immediately after injury, with P values below 0.05. (5) The percentages of GATA-3 positive cells in Th1 and Th2 were significantly positively correlated with those of ANXA1 (with r values respectively 0.747 and 0.787, P values below 0.05). CONCLUSIONS: The expression levels of ANXA1, GATA-3, and T-bet were continuously lowered in burned mice with sepsis, and it may play an important role in Th1/Th2 balance switching to Th2 bias and immunosuppressive process. PMID- 26902276 TI - [Effects of microRNA-146a on Fas-associated factor 2 and inflammatory factors in human lung adenocarcinoma A549 cells under the stimulation of cigarette smoke extract]. AB - OBJECTIVE: Under the premise of smoke inhalation injury, to explore the effects of microRNA-146a on Fas-associated factor 2 (FAF-2) and inflammatory factors in human lung adenocarcinoma A549 cells under the stimulation of cigarette smoke extract (CSE). METHODS: (1) The pMIR-FAF-2 recombinant plasmid and the pMIR-FAF-2 recombinant mutated plasmid were constructed. Human embryonic kidney 293 (HEK 293) cells of the third passage were divided into 3 groups according to the random number table, with 5 wells in each group. Cells in plasmid+ microRNA control group were transfected with pMIR-FAF-2 recombinant plasmid, pRL-TK plasmid, and microRNA control; cells in plasmid+ microRNA-146a group were transfected with pMIR-FAF-2 recombinant plasmid, pRL-TK plasmid, and microRNA 146a mimics; cells in mutated plasmid+ microRNA-146a group were transfected with pMIR-FAF-2 recombinant mutated plasmid, pRL-TK plasmid, and microRNA-146a inhibitor. After culture for 24 h, the relative luciferase activity in cells was assessed by dual-luciferase reporter gene assay. (2) Human lung adenocarcinoma A549 cells of the third passage were divided into 3 groups according to the random number table, with 4 wells in each group. Cells in microRNA control group were transfected with microRNA control; cells in microRNA-146a enhancement group were transfected with microRNA-146a mimics; cells in microRNA-146a inhibition group were transfected with microRNA-146a inhibitor. After culture for 24 h, the mRNA expression levels of microRNA-146a and FAF-2 in cells were determined with real-time fluorescent quantitative reverse transcription-PCR. (3) A549 cells of the third passage were stimulated by 0.8% CSE for 24 h after being divided and treated with the same method used in experiment (2). The mRNA expression levels of FAF-2, IL-8, monocyte chemotactic protein-1 (MCP-1), and growth-regulated oncogene-alpha (GRO-alpha) in cells were determined with real-time fluorescent quantitative reverse transcription-PCR. The protein expression levels of IL-8, MCP-1, and GRO-alpha in A549 cell culture supernatant were determined by enzyme linked immunosorbent assay. The protein expression level of cyclooxygenase 2 (COX 2) of cells was assessed by Western blotting. Data were processed with one-way analysis of variance and LSD test. RESULTS: (1) The pMIR-FAF-2 recombinant plasmid and pMIR-FAF-2 recombinant mutated plasmid were confirmed with successful construction. The relative luciferase activity in HEK-23 cells of plasmid+ microRNA control group was close to that of mutated plasmid+ microRNA-146a group (P>0.05). The relative luciferase activity in HEK-23 cells of plasmid+ microRNA 146a group was significantly lower than that of plasmid+ microRNA control group and mutated plasmid+ microRNA-146a group (with P values below 0.01). (2) The expression level of microRNA-146a in A549 cells of microRNA control group was close to that of microRNA-146a inhibition group (P>0.05), and they were both significantly lower than the expression level of microRNA-146a in A549 cells of microRNA-146a enhancement group (with P values below 0.01). The mRNA expression level of FAF-2 in A549 cells of microRNA control group was close to that of microRNA-146a inhibition group (P>0.05), and they were both significantly higher than the mRNA expression level of FAF-2 in A549 cells of microRNA-146a enhancement group (with P values below 0.05). (3) After stimulation of CSE, the mRNA expression level of FAF-2 in A549 cells of microRNA control group (1.46+/ 0.21) was close to that of microRNA-146a inhibition group (1.43+/-0.34, P>0.05), which were both significantly higher than the mRNA expression level of FAF-2 in A549 cells of microRNA-146a enhancement group (0.57+/-0.11, with P values below 0.05). The mRNA expression levels of IL-8, MCP-1, and GRO-alpha in A549 cells of microRNA-146a enhancement group were significantly lower than those of microRNA control group and microRNA-146a inhibition group (with P values below 0.01). The mRNA expression levels of IL-8, MCP-1, and GRO-alpha in A549 cells of microRNA 146a inhibition group were significantly higher than those of microRNA control group (with P values below 0.05). The protein expression levels of IL-8, MCP-1, and GRO-alpha in A549 cell culture supernatant of microRNA-146a enhancement group were significantly lower than those of microRNA control group and microRNA-146a inhibition group (with P values below 0.05). The protein expression level of IL-8 in A549 cell culture supernatant of microRNA-146a inhibition group was close to that of microRNA control group (P>0.05), while the protein expression levels of MCP-1 and GRO-alpha in A549 cell culture supernatant of microRNA-146a inhibition group were significantly lower than those of microRNA control group (with P values below 0.05). The protein expression level of COX-2 in A549 cells of microRNA-146a enhancement group was significantly lower than the levels of microRNA control group and microRNA-146a inhibition group (with P values below 0.05). The protein expression level of COX-2 in A549 cells of microRNA control group was close to that of microRNA-146a inhibition group (P>0.05). CONCLUSIONS: In A549 cells, after being transfected with microRNA-146a and stimulated by CSE, microRNA-146a can decrease the expression of FAF-2 through integrating with the 3'-untranslated region of target gene FAF-2, thereby decrease the expression of inflammatory factors. PMID- 26902277 TI - [Predictive value of combining of anatomy scoring system and physiological scoring system for the diagnosis of multiple organ dysfunction syndrome in patients with severe trauma]. AB - OBJECTIVE: To evaluate the predictive value of a combination of anatomy scoring system and physiological scoring system for the diagnosis of multiple organ dysfunction syndrome (MODS) in patients with severe trauma. METHODS: The clinical data of 539 patients with severe trauma hospitalized in ICUs of the First Affiliated Hospital of Chengdu Medical College, Daping Hospital of the Third Military Medical University, and the Affiliated Hospital of Zunyi Medical College from January 2010 to December 2014, conforming to the study criteria, were retrospectively analyzed. The patients were divided into MODS group (n=361) and non-MODS group (n=178) according to the diagnostic criteria of MODS. The data of Injury Severity Score (ISS), New Injury Severity Score (NISS), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, ISS+ APACHE II score, and NISS+ APACHE II score of patients on the first day of ICU admission were calculated and compared between the two groups. Data were processed with t test, chi-square test, and receiver operating characteristic (ROC) curves of the various scoring systems in 539 patients with severe trauma were plotted, and DeLong-DeLong non parametric test was used to evaluate the predictive ability for MODS of the various scoring systems. RESULTS: The scores of ISS, NISS, APACHE II, ISS+ APACHE II, and NISS+ APACHE II of patients in MODS group were respectively (26+/-8), (36+/-12), (21+/-7), (47+/-10), and (56+/-14) points, and they were significantly higher than those of patients in non-MODS group [respectively (24+/ 6), (28+/-7), (16+/-5), (39+/-8), and (44+/-9) points, with t values from 4.970 to 12.120, P values below 0.01]. The total areas under ROC curves (95% confidence interval) of ISS, NISS, APACHE II score, ISS+ APACHE II score, and NISS+ APACHE II score in MODS prediction of patients with severe trauma were respectively 0.611 (0.569-0.653), 0.693 (0.652-0.731), 0.719 (0.679-0.756), 0.727 (0.687 0.764), and 0.764 (0.726-0.799). The total areas under ROC curves of NISS, APACHE II score, ISS+ APACHE II score, and NISS+ APACHE II score were significantly larger than the total area under ROC curve of ISS (with Z values from 3.505 to 7.179, P values below 0.001). The total areas under ROC curves of APACHE II score and ISS+ APACHE II score were larger than the total area under ROC curve of NISS, but there were no significant differences (with Z values respectively 0.931 and 1.657, P values above 0.05), while the total area under ROC curve of NISS+ APACHE II score was significantly larger than that of NISS (Z=5.478, P<0.001). The total area under ROC curve of ISS+ APACHE II score was larger than that of APACHEII score, but there was no significant difference (Z=0.450, P=0.653), and the total area under ROC curve of NISS+ APACHE II score was significantly larger than that of APACHE II score (Z=2.554, P<0.05). The total area under ROC curve of NISS+ APACHE II score was significantly larger than that of ISS+ APACHE II score (Z=2.989, P<0.01). CONCLUSIONS: The combination of NISS and APACHE II score is more significant than ISS, NISS, APACHE II score, and ISS+ APACHE II score in prediction of MODS in patients with severe trauma. PMID- 26902278 TI - [Advances in the research of mechanism of protein ubiquitination in wound healing]. AB - Ubiquitin, a critical small molecular protein, plays an important role in regulating multiple signaling pathways. Ubiquitination is a post-translational modification induced by ubiquitin through an ATP-dependent enzyme catalyzed reaction. A large number of proteins in the complicated signaling network participate in wound healing. This paper reviews the research progress in regulation of ubiquitin and ubiquitination for wound healing processes regarding the recent years. PMID- 26902279 TI - [Advances in the research of pathogenesis and treatment of severe smoke inhalation injury]. AB - Among the fire victims, respiratory tract injury resulted from smoke inhalation is the major cause of death. Particulate substances in smoke, toxic and harmful gas, and chemical substances act together would rapidly induce the occurrence of dramatic pathophysiologic reaction in the respiratory tract, resulting in acute injury to the respiratory tract, thus inducing serious injury to it and acute respiratory distress syndrome, leading to death of the victims. In recent years, the pathophysiologic mechanism of severe smoke inhalation injury has been gradually clarified, thus appreciable advances in its treatment have been achieved. This paper is a brief review of above-mentioned aspects. PMID- 26902280 TI - [Structure, function and reconstruction of skin surface lipid film]. AB - After healing of burn wound, skin of scar, transplanted skin grafts, and healed donor site wound suffer from temporary or permanent loss of function of sebaceous glands and dysfunction of skin surface lipid film formation, resulting in desiccation, desquamation, and sensitiveness of the skin, making areas of newly formed skin unsatisfactory. Therefore a good rehabilitation may fail. In this paper, the composition, physiochemical properties, and reconstruction of skin surface lipid film are discussed. PMID- 26902281 TI - Duloxetine Add-On to Risperidone for Treatment of Negative Symptoms in Patients with Stable Schizophrenia: Randomized Double-Blind Placebo-Controlled Study. AB - INTRODUCTION: Although the pathogenesis of symptoms of schizophrenia is largely unknown, a variety of neurotransmitters are implicated, including serotonin and norepinephrine. Here we investigate the effectiveness of duloxetine as a serotonin-norepinephrine inhibitor in the treatment of negative symptoms. METHODS: We performed a double-blind clinical trial on 64 patients with stable schizophrenia and no prominent symptoms of depression. Patients received risperidone (up to 6 mg/day) plus either duloxetine (60 mg/day) or placebo. Psychotic symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS) at the onset of the trial, and at 2, 4, 6 and 8 weeks of therapy. RESULTS: Compared to the placebo group, the duloxetine group showed significantly higher improvement in negative symptoms (p<0.001), PANSS total (p<0.001), and the general psychopathology subscale scores (p=0.001), but no significant difference in positive symptoms (p=0.13). The side effect profiles of the 2 treatment regimens were not significantly different. DISCUSSION: Duloxetine adjuvant to risperidone seems to be a tolerable and efficacious treatment for primary negative symptoms of schizophrenia. PMID- 26902282 TI - Effects of Adrenomedullin on Doxorubicin-Induced Cardiac Damage in Mice. AB - Doxorubicin (DOX) is one of the best known anticancer drugs, and is used in the treatment of lymphoma, lung cancer, stomach cancer, and a number of other cancers. However, DOX has some serious side effects, the worst being lethal heart failure. Occasionally, its side effects result in the cessation of the anticancer treatment, thus having a serious adverse influence on prognosis. Agents that can be administered as alternative prophylactics or to ameliorate the side effects of DOX will be useful in increasing the safety and efficacy of anticancer therapy. Adrenomedullin (AM) is a peptide hormone secreted by many organs, including the heart; it has an organ-protective effect, including antiapoptotic, anti inflammatory, and antioxidative stress. Blood AM levels increase with heart failure; endogenic AM has been suggested in order to protect the heart. Furthermore, exogenous AM administration has shown therapeutic effects for heart failure in patients. However, it is unclear whether AM can protect the heart against drug-induced cardiac injury in vivo. The present study was performed in order to investigate the effects of AM on DOX-induced cardiac damage. Male BALB/c mice were treated with DOX and/or AM. Exogenous AM improved the survival ratio of DOX-treated mice. In addition, AM reduced serum lactate dehydrogenase (LDH) levels following DOX treatment. On pathological examination, AM was shown to inhibit DOX-induced cardiac tissue damage, mitochondrial abnormality, and cell death. These findings suggest that AM has a protective effect against DOX-induced cardiac damage. PMID- 26902283 TI - Single-cell triple omics sequencing reveals genetic, epigenetic, and transcriptomic heterogeneity in hepatocellular carcinomas. AB - Single-cell genome, DNA methylome, and transcriptome sequencing methods have been separately developed. However, to accurately analyze the mechanism by which transcriptome, genome and DNA methylome regulate each other, these omic methods need to be performed in the same single cell. Here we demonstrate a single-cell triple omics sequencing technique, scTrio-seq, that can be used to simultaneously analyze the genomic copy-number variations (CNVs), DNA methylome, and transcriptome of an individual mammalian cell. We show that large-scale CNVs cause proportional changes in RNA expression of genes within the gained or lost genomic regions, whereas these CNVs generally do not affect DNA methylation in these regions. Furthermore, we applied scTrio-seq to 25 single cancer cells derived from a human hepatocellular carcinoma tissue sample. We identified two subpopulations within these cells based on CNVs, DNA methylome, or transcriptome of individual cells. Our work offers a new avenue of dissecting the complex contribution of genomic and epigenomic heterogeneities to the transcriptomic heterogeneity within a population of cells. PMID- 26902284 TI - saRNA-guided Ago2 targets the RITA complex to promoters to stimulate transcription. AB - Small activating RNAs (saRNAs) targeting specific promoter regions are able to stimulate gene expression at the transcriptional level, a phenomenon known as RNA activation (RNAa). It is known that RNAa depends on Ago2 and is associated with epigenetic changes at the target promoters. However, the precise molecular mechanism of RNAa remains elusive. Using human CDKN1A (p21) as a model gene, we characterized the molecular nature of RNAa. We show that saRNAs guide Ago2 to and associate with target promoters. saRNA-loaded Ago2 facilitates the assembly of an RNA-induced transcriptional activation (RITA) complex, which, in addition to saRNA-Ago2 complex, includes RHA and CTR9, the latter being a component of the PAF1 complex. RITA interacts with RNA polymerase II to stimulate transcription initiation and productive elongation, accompanied by monoubiquitination of histone 2B. Our results establish the existence of a cellular RNA-guided genome targeting and transcriptional activation mechanism and provide important new mechanistic insights into the RNAa process. PMID- 26902285 TI - Oocyte-expressed yes-associated protein is a key activator of the early zygotic genome in mouse. AB - In early mammalian embryos, the genome is transcriptionally quiescent until the zygotic genome activation (ZGA) which occurs 2-3 days after fertilization. Despite a long-standing effort, maternal transcription factors regulating this crucial developmental event remain largely elusive. Here, using maternal and paternal mouse models of Yap1 deletion, we show that maternally accumulated yes associated protein (YAP) in oocyte is essential for ZGA. Maternal Yap1-knockout embryos exhibit a prolonged two-cell stage and develop into the four-cell stage at a much slower pace than the wild-type controls. Transcriptome analyses identify YAP target genes in early blastomeres; two of which, Rpl13 and Rrm2, are required to mediate maternal YAP's effect in conferring developmental competence on preimplantation embryos. Furthermore, the physiological YAP activator, lysophosphatidic acid, can substantially improve early development of wild-type, but not maternal Yap1-knockout embryos in both oviduct and culture. These observations provide insights into the mechanisms of ZGA, and suggest potentials of YAP activators in improving the developmental competence of cultured embryos in assisted human reproduction and animal biotechnology. PMID- 26902286 TI - tRNA fragments: novel players in intergenerational inheritance. AB - Non-genetic inheritance is an evocative topic; in the past few years, the debate around potential inheritance of life-time experiences independent of social factors in mammals has become highly prominent due to increasing evidence for phenotypes in the offspring after paternal environmental exposures. Strikingly, two independent studies published in Science newly implicate a special class of RNA, transfer RNA fragments, in the intergenerational effects of paternal dietary intervention. PMID- 26902287 TI - An Ebola virus-encoded microRNA-like fragment serves as a biomarker for early diagnosis of Ebola virus disease. PMID- 26902288 TI - Keeping homologous recombination in check. AB - Pathway choice is a critical event in the repair of DNA double-strand breaks. In a recent paper published in Nature, Orthwein et al. define a mechanism by which homologous recombination is controlled in G1 cells to favor non-homologous end joining. PMID- 26902289 TI - Visual Prognosis and Associated Factors of Phacoemulsification and Intraocular Lens Implantation in Different Uveitis Entities in Han Chinese. AB - PURPOSE: To address the visual prognosis and associated predictors of phacoemulsification and intraocular lens implantation in different uveitis entities in Han Chinese. METHODS: A retrospective review of the uveitis patients who underwent phacoemulsification and intraocular lens implantation in our center between 2004 and 2014. RESULTS: The 158 patients (226 eyes) included anterior uveitis (45 eyes), posterior/pan-uveitis (61 eyes), Vogt-Koyanagi-Harada disease (79 eyes) and Behcet disease (41 eyes). At 6 months after surgery, best-corrected visual acuity (BCVA) significantly improved (p < 0.001) in all uveitis groups with 134 (59.3%) eyes achieving 20/40 or better. The anterior uveitis and Behcet disease groups had significantly better and worse visual outcomes than other groups, respectively. Poor preoperative BCVA, macular lesions, and secondary glaucoma were independent variables that predicted a poor visual outcome. CONCLUSIONS: Our current study revealed a generally favorable outcome and associated predictors of phacoemulsification and intraocular lens implantation in uveitic cataracts in Han Chinese. PMID- 26902290 TI - Visual monitoring of goal-directed aiming movements. AB - Goal-directed movements are subject to intrinsic planning and execution variability, which requires that the central nervous system closely monitor our movements to ensure endpoint accuracy. In the present study, we sought to determine how closely the visual system monitored goal-directed aiming movements. We used a cursor-jump paradigm in which a cursor was unexpectedly translated soon after movement initiation. Some of the trials included a second cursor jump, and the cursor remained visible for different durations. The results indicate that seeing the cursor for only 16 ms after the second cursor jump was sufficient to influence the movement endpoint, which suggests that the visual system continuously monitored goal-directed movements. The results also suggest that the perceived position/trajectory of the effector was likely to have been averaged over a period of approximately 70 ms. PMID- 26902291 TI - The ability of four strains of Streptococcus uberis to induce clinical mastitis after intramammary inoculation in lactating cows. AB - AIM: To compare the ability of four strains of Streptococcus uberis at two doses to induce clinical mastitis in lactating dairy cows after intramammary inoculation in order to evaluate their usefulness for future experimental infection models. MATERIALS AND METHODS: Four field strains of S. uberis (26LB, S418, and S523 and SR115) were obtained from cows with clinical mastitis in the Wairarapa and Waikato regions of New Zealand. Twenty-four crossbred lactating cows, with no history of mastitis and absence of major pathogens following culture of milk samples, were randomly allocated to four groups (one per strain) of six cows. Each cow was infused (Day 0) in one quarter with approximately 10(4) cfu and in the contralateral quarter with approximately 10(6) cfu of the same strain. The other two quarters remained unchallenged. All four quarters were then inspected for signs of clinical mastitis, by palpation and observation of the foremilk, twice daily from Days 0-9, and composite milk samples were collected from Days 0-8 for analysis of somatic cell counts (SCC). Quarters were treated with penicillin when clinical mastitis was observed. Duplicate milk samples were collected and cultured on presentation of each clinical case and on Day 4 from challenged quarters with no clinical signs. RESULTS: Clinical mastitis was diagnosed in 26/48 (54%) challenged quarters. Challenge with strain S418 resulted in more cases of mastitis (12/12 quarters) than strains SR115 (7/12), 26LB (6/12) or S523 (1/12), and the mean interval from challenge to first diagnosis of mastitis was shorter for S418 than the other strains (p<0.001). The proportion of quarters from which S. uberis could be isolated after challenge was less for strain 26LB (1/6) than SR115 (6/7) (p<0.05), and SCC following challenge was lower for strain S523 than the other strains (p<0.05). CONCLUSIONS: There were significant differences between the strains in the proportion of quarters developing clinical mastitis, the interval to mastitis onset, SCC following challenge and the proportion of clinical cases from which S. uberis could be isolated. These results illustrate the difference in the ability of S. uberis strains to cause mastitis and the severity of the infections caused. CLINICAL RELEVANCE: Experimental challenge models can be used to compare infectivity and pathogenicity of different strains of mastitis-causing bacteria, the efficacy of pharmaceutical products and host-responses in a cost-effective manner. PMID- 26902292 TI - Temporal and spatial distribution of macrophage phenotype markers in the foreign body response to glutaraldehyde-crosslinked gelatin hydrogels. AB - Currently, it is not well understood how changes in biomaterial properties affect the foreign body response (FBR) or macrophage behavior. Because failed attempts at biomaterial degradation by macrophages have been linked to frustrated phagocytosis, a defining feature of the FBR, we hypothesized that increased hydrogel crosslinking density (and decreased degradability) would exacerbate the FBR. Gelatin hydrogels were crosslinked with glutaraldehyde (0.05, 0.1, and 0.3%) and implanted subcutaneously in C57BL/6 mice over the course of 3 weeks. Interestingly, changes in hydrogel crosslinking did not affect the thickness of the fibrous capsule surrounding the hydrogels, expression of the pan-macrophage marker F480, expression of three macrophage phenotype markers (iNOS, Arg1, CD163), or expression of the myofibroblast marker aSMA, determined using semi quantitative immunohistochemical analysis. With respect to temporal changes, the level of expression of the M1 marker (iNOS) remained relatively constant throughout the study, while the M2 markers Arg1 and CD163 increased over time. Expression of these M2 markers was highly correlated with fibrous capsule thickness. Differences in spatial distribution of staining also were noted, with the strongest staining for iNOS at the hydrogel surface and increasing expression of the myofibroblast marker aSMA toward the outer edge of the fibrous capsule. These results confirm previous reports that macrophages in the FBR exhibit characteristics of both M1 and M2 phenotypes. Understanding the effects (or lack of effects) of biomaterial properties on the FBR and macrophage phenotype may aid in the rational design of biomaterials to integrate with surrounding tissue. PMID- 26902294 TI - An online hybrid BCI system based on SSVEP and EMG. AB - OBJECTIVE: A hybrid brain-computer interface (BCI) is a device combined with at least one other communication system that takes advantage of both parts to build a link between humans and machines. To increase the number of targets and the information transfer rate (ITR), electromyogram (EMG) and steady-state visual evoked potential (SSVEP) were combined to implement a hybrid BCI. A multi-choice selection method based on EMG was developed to enhance the system performance. APPROACH: A 60-target hybrid BCI speller was built in this study. A single trial was divided into two stages: a stimulation stage and an output selection stage. In the stimulation stage, SSVEP and EMG were used together. Every stimulus flickered at its given frequency to elicit SSVEP. All of the stimuli were divided equally into four sections with the same frequency set. The frequency of each stimulus in a section was different. SSVEPs were used to discriminate targets in the same section. Different sections were classified using EMG signals from the forearm. Subjects were asked to make different number of fists according to the target section. Canonical Correlation Analysis (CCA) and mean filtering was used to classify SSVEP and EMG separately. In the output selection stage, the top two optimal choices were given. The first choice with the highest probability of an accurate classification was the default output of the system. Subjects were required to make a fist to select the second choice only if the second choice was correct. MAIN RESULTS: The online results obtained from ten subjects showed that the mean accurate classification rate and ITR were 81.0% and 83.6 bits min(-1) respectively only using the first choice selection. The ITR of the hybrid system was significantly higher than the ITR of any of the two single modalities (EMG: 30.7 bits min(-1), SSVEP: 60.2 bits min(-1)). After the addition of the second choice selection and the correction task, the accurate classification rate and ITR was enhanced to 85.8% and 90.9 bit min(-1). SIGNIFICANCE: These results suggest that the hybrid system proposed here is suitable for practical use. PMID- 26902293 TI - Embodied perspective-taking indicated by selective disruption from aberrant self motion. AB - Spatial perspective-taking that involves imagined changes in one's spatial orientation is facilitated by vestibular stimulation inducing a congruent sensation of self-motion. We examined further the role of vestibular resources in perspective-taking by evaluating whether aberrant and conflicting vestibular stimulation impaired perspective-taking performance. Participants (N = 39) undertook either an "own body transformation" (OBT) task, requiring speeded spatial judgments made from the perspective of a schematic figure, or a control task requiring reconfiguration of spatial mappings from one's own visuo-spatial perspective. These tasks were performed both without and with vestibular stimulation by whole-body Coriolis motion, according to a repeated measures design, balanced for order. Vestibular stimulation was found to impair performance during the first minute post stimulus relative to the stationary condition. This disruption was task-specific, affecting only the OBT task and not the control task, and dissipated by the second minute post-stimulus. Our experiment thus demonstrates selective temporary impairment of perspective-taking from aberrant vestibular stimulation, implying that uncompromised vestibular resources are necessary for efficient perspective-taking. This finding provides evidence for an embodied mechanism for perspective-taking whereby vestibular input contributes to multisensory processing underlying bodily and social cognition. Ultimately, this knowledge may contribute to the design of interventions that help patients suffering sudden vertigo adapt to the cognitive difficulties caused by aberrant vestibular stimulation. PMID- 26902295 TI - A Review of HIV Prevention Studies that Use Social Networking Sites: Implications for Recruitment, Health Promotion Campaigns, and Efficacy Trials. AB - This review describes the use of social networking sites (SNS) in the context of primary prevention of HIV. A review was conducted to assess the published literature for HIV interventions using SNS. Sixteen articles describing twelve interventions were included. SNS were instrumental in recruiting hard-to-reach populations within a short amount of time; were able to reach wide audiences beyond the targeted population for HIV prevention campaigns; and helped to significantly reduce sexual risk behaviors and increase HIV testing. SNS are a viable option to recruit hidden populations, engage the target audience, and disseminate HIV prevention messages. Researchers should use SNS to generate sampling frames that can be used to select participants. Practitioners should use SNS to post images of preventive behavior within health promotion campaigns. Researchers should use multiple SNS platforms to engage participants. As more studies are published using SNS for HIV prevention, meta-analyses will be needed. PMID- 26902296 TI - Comparison of two single-breath-held 3-D acquisitions with multi-breath-held 2-D cine steady-state free precession MRI acquisition in children with single ventricles. AB - BACKGROUND: Breath-held two-dimensional balanced steady--state free precession cine acquisition (2-D breath-held SSFP), accelerated with parallel imaging, is the method of choice for evaluating ventricular function due to its superior blood-to-myocardial contrast, edge definition and high intrinsic signal-to-noise ratio throughout the cardiac cycle. OBJECTIVE: The purpose of this study is to qualitatively and quantitatively compare the two different single-breath-hold 3-D cine SSFP acquisitions using 1) multidirectional sensitivity encoding (SENSE) acceleration factors (3-D multiple SENSE SSFP), and 2) k-t broad-use linear acceleration speed-up technique (3-D k-t SSFP) with the conventional 2-D breath held SSFP in non-sedated asymptomatic volunteers and children with single ventricle congenital heart disease. MATERIALS AND METHODS: Our prospective study was performed on 30 non-sedated subjects (9 healthy volunteers and 21 functional single ventricle patients), ages 12.5 +/- 2.8 years. Two-dimensional breath-held SSFP with SENSE acceleration factor of 2, eight-fold accelerated 3-D k-t SSFP, and 3-D multiple SENSE SSFP with total parallel imaging factor of 4 were performed to evaluate ventricular volumes and mass in the short-axis orientation. Image quality scores (blood myocardial contrast, edge definition and interslice alignment) and volumetric analysis (end systolic volume, end diastolic volume and ejection fraction) were performed on the data sets by experienced users. Paired t test was performed to compare each of the 3-D k-t SSFP and 3-D multiple SENSE SSFP clinical scores against 2-D breath-held SSFP. Bland-Altman analysis was performed on left ventricle (LV) and single ventricle volumetry. Interobserver and intraobserver variability in volumetric measurements were determined using intraclass coefficients. RESULTS: The clinical scores were highest for the 2-D breath-held SSFP images. Between the two 3-D sequences, 3-D multiple SENSE SSFP performed better than 3-D k-t SSFP. Bland-Altman analysis for volumes indicated that variability was more between 3-D k-t SSFP and 2-D breath-held SSFP acquisitions than between 3-D multiple SENSE SSFP and 2-D breath-held SSFP acquisitions. In the non-sedated population, interslice alignment scores were better for 3-D k-t SSFP and 3-D multiple SENSE SSFP than 2-D breath-held SSFP. The blood-myocardial contrast and edge definition scores were better for 2-D breath-held SSFP than 3-D k-t SSFP and 3-D multiple SENSE SSFP. Scan duration was shorter for 3-D acquisition sequences compared to the 2-D breath-held stack. CONCLUSION: Three-dimensional k-t SSFP and 3-D multiple SENSE for ventricular volumetry release the constraints of multiple breath-holds in children and overcome problems related to interslice misalignment caused by inconsistent amplitude of breathing. Three-dimensional multiple SENSE SSFP performed better in our pediatric population than 3-D k-t SSFP. However, these 3-D sequences produce lower-quality diagnostic images than the gold standard 2-D breath-held SSFP sequence. PMID- 26902297 TI - Patellofemoral instability in children: T2 relaxation times of the patellar cartilage in patients with and without patellofemoral instability and correlation with morphological grading of cartilage damage. AB - BACKGROUND: Patellofemoral instability is one of the most common causes of cartilage damage in teenagers. OBJECTIVE: To quantitatively evaluate the patellar cartilage in patients with patellofemoral instability using T2 relaxation time maps (T2 maps), compare the values to those in patients without patellofemoral instability and correlate them with morphological grades in patients with patellofemoral instability. MATERIALS AND METHODS: Fifty-three patients with patellofemoral instability (mean age: 15.9 +/- 2.4 years) and 53 age- and gender matched patients without patellofemoral instability were included. Knee MR with axial T2 map was performed. Mean T2 relaxation times were obtained at the medial, central and lateral zones of the patellar cartilage and compared between the two groups. In the patellofemoral instability group, morphological grading of the patellar cartilage (0-4) was performed and correlated with T2 relaxation times. RESULTS: Mean T2 relaxation times were significantly longer in the group with patellofemoral instability as compared to those of the control group across the patellar cartilage (Student's t-test, P<0.05) with the longest time at the central area. Positive correlation was seen between mean T2 relaxation time and morphological grading (Pearson correlation coefficiency, P<0.001). T2 increased with severity of morphological grading from 0 to 3 (mixed model, P<0.001), but no statistical difference was seen between grades 3 and 4. CONCLUSION: In patellofemoral instability, patellar cartilage damage occurs across the entire cartilage with the highest T2 values at the apex. T2 relaxation times directly reflect the severity in low-grade cartilage damage, which implies an important role for T2 maps in differentiating between normal and low-grade cartilage damage. PMID- 26902298 TI - Cryoablation in fibro-adipose vascular anomaly (FAVA): a minimally invasive treatment option. AB - BACKGROUND: Fibro-adipose vascular anomaly (FAVA) is a complex vascular malformation that typically presents with persistent pain, discomfort, contracture and other disabling symptoms. There are no minimally invasive treatment options to effectively control these symptoms. Image-guided percutaneous cryoablation, which has been used to control pain in people with cancer, could be used for similar indications in FAVA. OBJECTIVE: To assess the role of image-guided percutaneous cryoablation for control of symptoms in FAVA lesions. MATERIALS AND METHODS: We conducted a retrospective cohort study of 20 children and young adults with FAVA who underwent percutaneous cryoablation at 26 sites, from September 2013 to August 2015. The outcome was based on the brief pain inventory scoring (BPI), concurrent symptoms, clinical response and patient satisfaction. RESULTS: After cryoablation there was significant improvement in pain, which dropped by 3 points (pain now) to 3.7 points (pain in the last 24 h). Most patients indicated that pain interfered less in their everyday social life. Concurrent symptoms like swelling, physical limitations and skin hyperesthesia also improved. Clinical response was greatest at 2-5 months follow-up after cryoablation, with acceptable patient satisfaction thereafter. Technical response was 100%. There were no major complications. CONCLUSION: Image-guided percutaneous cryoablation is a safe and effective option for treatment of symptomatic FAVA lesions. PMID- 26902299 TI - The classic metaphyseal lesion and traumatic injury. AB - BACKGROUND: It is widely accepted that the classic metaphyseal lesion (CML) is a traumatic lesion, strongly associated with abuse in infants. Nevertheless, various non-traumatic origins for CMLs continue to be suggested in medical and legal settings. No studies to date systematically describe the association of CMLs with other traumatic injuries. OBJECTIVE: The primary objective of this study is to examine the association of CMLs with other traumatic injuries in a large data set of children evaluated for physical abuse. MATERIALS AND METHODS: This was a retrospectively planned secondary analysis of data from a prospective, observational study of children <120 months of age who underwent evaluation by a child abuse physician. For this secondary analysis, we identified all children <=12 months of age with an identified CML and determined the number and type of additional injuries identified. Descriptive analysis was used to report frequency of additional traumatic injuries. RESULTS: Among 2,890 subjects, 119 (4.1%) were identified as having a CML. Of these, 100 (84.0%) had at least one additional (non-CML) fracture. Thirty-three (27.7%) had traumatic brain injury. Nearly half (43.7%) of children had cutaneous injuries. Oropharyngeal injuries were found in 12 (10.1%) children. Abdominal/thoracic injuries were also found in 12 (10.1%) children. In all, 95.8% of children with a CML had at least one additional injury; one in four children had three or more categories of injury. CONCLUSION: CMLs identified in young children are strongly associated with traumatic injuries. Identification of a CML in a young child should prompt a thorough evaluation for physical abuse. PMID- 26902300 TI - Diagnosis of vertebral fractures in children: is a simplified algorithm-based qualitative technique reliable? AB - BACKGROUND: Identification of osteoporotic vertebral fractures allows treatment opportunity reducing future risk. There is no agreed standardised method for diagnosing paediatric vertebral fractures. OBJECTIVE: To evaluate the precision of a modified adult algorithm-based qualitative (ABQ) technique, applicable to children with primary or secondary osteoporosis. MATERIALS AND METHODS: Three radiologists independently assessed lateral spine radiographs of 50 children with suspected reduction in bone mineral density using a modified ABQ scoring system and following simplification to include only clinically relevant parameters, a simplified ABQ score. A final consensus of all observers using simplified ABQ was performed as a reference standard for fracture characterisation. Kappa was calculated for interobserver agreement of the components of both scoring systems and intraobserver agreement of simplified ABQ based on a second read of 29 randomly selected images. RESULTS: Interobserver Kappa for modified ABQ scoring for fracture detection, severity and shape ranged from 0.34 to 0.49 Kappa for abnormal endplate and position assessment was 0.27 to 0.38. Inter- and intraobserver Kappa for simplified ABQ scoring for fracture detection and grade ranged from 0.37 to 0.46 and 0.45 to 0.56, respectively. Inter- and intraobserver Kappa for affected endplate ranged from 0.31 to 0.41 and 0.45 to 0.51, respectively. Subjectively, observers' felt simplified ABQ was easier and less time-consuming. CONCLUSION: Observer reliability of modified and simplified ABQ was similar, with slight to moderate agreement for fracture detection and grade/severity. Due to subjective preference for simplified ABQ, we suggest its use as a semi-objective measure of diagnosing paediatric vertebral fractures. PMID- 26902301 TI - Regulator of G-protein Signaling (RGS)1 and RGS10 Proteins as Potential Drug Targets for Neuroinflammatory and Neurodegenerative Diseases. AB - Regulator of G-protein signaling (RGS) proteins were originally identified as negative regulators of G-protein-coupled receptor (GPCR) signaling via their GTPase-accelerating protein (GAP) activity. All RGS proteins contain evolutionarily conserved RGS domain; however, they differ in their size and regulatory domains. RGS1 and RGS10 are smaller than other RGS proteins, and their functions involve various inflammatory responses including autoimmune responses in both the periphery and the central nervous system (CNS). Neuroinflammation is the chronic inflammatory response in the CNS. Acute inflammatory response in the CNS is believed to be beneficial by involving the neuroprotective actions of immune cells in the brain, particularly microglia, to limit tissue damage and to aid in neuronal repair. However, chronically elevated levels of cytokines serve to maintain activation of abundant numbers of immune cells potentiating prolonged inflammatory responses and creating an environment of oxidative stress, which further hastens oxidative damage of neurons. In this review, we describe the implications and features of RGS proteins (specifically RGS1 and RGS10) in neuroinflammation and neurodegenerative diseases. We will discuss the experimental and epidemiological evidence on the benefits of anti-inflammatory interventions by targeting RGS1 and/or RGS10 protein function or expression in order to delay or attenuate the progression of neurodegeneration, particularly in multiple sclerosis (MS) and Parkinson's disease (PD). PMID- 26902304 TI - Dirac electrons in the presence of a matrix potential barrier: application to graphene and topological insulators. AB - Scattering of 2D Dirac electrons on a rectangular matrix potential barrier is considered using the formalism of spinor transfer matrices. It is shown, in particular, that in the absence of the mass term, the Klein tunneling is not necessarily suppressed but occurs at oblique incidence. The formalism is applied to studying waveguiding modes of the barrier, which are supported by the edge and bulk states. The condition of the existence of the uni-directionality property is found. We show that the band of edge states is always finite with massless excitations, while the spectrum of the bulk states, depending on the parameters of the barrier, may consist of the infinite or finite band with both, massive and massless, low-energy excitations. The effect of the Zeeman term is considered and the condition of the appearance of two distinct energy-dependent directions corresponding to the Klein tunneling is found. PMID- 26902302 TI - Aggregation Kinetics for IgG1-Based Monoclonal Antibody Therapeutics. AB - Monoclonal antibodies (mAbs) as a class of therapeutic molecules are finding an increasing demand in the biotechnology industry for the treatment of diseases like cancer and multiple sclerosis. A key challenge associated to successful commercialization of mAbs is that from the various physical and chemical instabilities that are inherent to these molecules. Out of all probable instabilities, aggregation of mAbs has been a major problem that has been associated with a change in the protein structure and is a hurdle in various upstream and downstream processes. It can stimulate immune response causing protein misfolding having deleterious and harmful effects inside a cell. Also, the extra cost incurred to remove aggregated mAbs from the rest of the batch is huge. Size exclusion chromatography (SEC) is a major technique for characterizing aggregation in mAbs where change in the aggregates' size over time is estimated. The current project is an attempt to understand the rate and mechanism of formation of higher order oligomers when subjected to different environmental conditions such as buffer type, temperature, pH, and salt concentration. The results will be useful in avoiding the product exposure to conditions that can induce aggregation during upstream, downstream, and storage process. Extended Lumry-Eyring model (ELE), Lumry-Eyring Native Polymerization model (LENP), and Finke-Watzky model (F-W) have been employed in this work to fit the aggregation experimental data and results are compared to find the best fit model for mAb aggregation to connect the theoretical dots with the reality. PMID- 26902303 TI - Trait "pessimism" is associated with increased sensitivity to negative feedback in rats. AB - Several cognitive theories of depression have proposed that cognitive judgment bias determines individual vulnerability to this disorder. Indeed, we have recently demonstrated a relationship between pessimistic judgment bias and vulnerability of rats to the stress-induced anhedonia, and a negative correlation between the level of pessimism and motivation. To further characterize the effects of trait pessimism on cognitive processes associated with depression, in the present study we compared the sensitivity of rats displaying optimistic and pessimistic traits to positive and negative feedback. The animals were initially trained and tested in the rat version of the probabilistic reversal-learning (PRL) task, which allowed for the assessment of feedback sensitivity in individual animals. Subsequently, the rats were re-trained and tested in a series of ambiguous-cue interpretation (ACI) tests, which allowed for the classification of animals displaying "optimistic" and "pessimistic" traits. The "pessimistic" rats were significantly more sensitive to negative feedback than their "optimistic" conspecifics, as indicated by an increased proportion of lose-shift behaviors. The results of our study demonstrate the interrelation and co existence of two cognitive biases that may predict vulnerability to depressive disorder. PMID- 26902305 TI - Pneumococcal Meningitis in the PCV13 Era: A Cluster of Cases With Increased Morbidity and Mortality. PMID- 26902306 TI - A Comparative Study of Intravenous Immunoglobulin and Subcutaneous Immunoglobulin in Adult Patients with Primary Immunodeficiency Diseases: A Systematic Review and Meta-Analysis. AB - Subcutaneous immunoglobulin (SCIG) is a new therapeutic procedure for patients with primary immunodeficiency (PI). This research is a systematic review of studies on the efficacy and safety of intravenous immunoglobulin (IVIG) and SCIG in adult patients with PI. This study includes a systematic review of cohorts and randomized clinical trials (24 articles) from 5 databases with no time limits. Random effects meta-analysis was performed for outcomes such as efficacy and safety. Standard mean difference (SMD) of serum immunoglobulin level was equal to 0.336 (P <0.01; 0.205-0.467) and the odds ratio (OR) of side effects was 0.497 (P=0.1; 0.180-1.371). The results indicate that SCIG leads to a higher level of immunoglobulin and a reduction in side effects but shows the same infection rate as IVIG. Our analysis shows that shifting from IVIG to SCIG therapy can have clinical benefits for PI patients. PMID- 26902308 TI - Qualities in friendship - Within an outside perspective - Definitions expressed by adolescents with mild intellectual disabilities. AB - BACKGROUND: This study examined how adolescents with mild intellectual disabilities define qualities of friendship and discussed the extent to which these definitions adhere to established definitions of close friendship. MATERIALS AND METHODS: The study was based on qualitative interviews with 11 adolescents in secondary school. The interviews were supplemented with information from six parents. A thematic structural analysis was used to identify themes. RESULTS: Qualities of friendship were categorized as mutual preference, mutual enjoyment, shared interactions, care, mutual trust and bonding. The criteria for close friendship seem to be fulfilled, albeit to a moderate degree. Closeness and reciprocity appear to be significant in this study, although these features have been considered less relevant within this target group in previous research. CONCLUSIONS: Differences in definitions may explain divergent results compared with other studies, and the need to achieve equivalence in friendship may be another. PMID- 26902307 TI - Effect of single-dose albendazole and vitamin A supplementation on the iron status of pre-school children in Sichuan, China. AB - The aim of this study was to explore the effect of single-dose albendazole and vitamin A intervention on the anaemic status and Fe metabolism of pre-school children. This study was a randomised, placebo-controlled and double-blinded intervention trial. All eligible anaemic pre-school children were randomly divided into three groups: group 1 received no intervention, which served as the control group, group 2 received 400 mg single-dose albendazole administration and group 3 received a 60000 MUg vitamin A capsule combined with 400 mg single-dose albendazole at the beginning of the study. The follow-up period was for 6 months. Anthropometry and biochemical index about Fe metabolism were measured before and after intervention. A total of 209 pre-school anaemic children were randomly divided into three intervention groups (sixty-four, sixty-two and sixty for groups 1, 2 and 3, respectively). The mean age of the children in the study was 4.4 (sd 0.7) years and 50.5 % of the children were female (94/186). After a follow-up period of 6 months, the levels of serum retinol, ferritin, transferrin receptor-ferritin index and body total Fe content of children in group 3 were significantly higher compared with children in groups 1 and 2 (P<0.05). Moreover, the proportion of vitamin A deficiency, marginal vitamin A deficiency and Fe deficiency among children in group 3 were markedly lower compared with children in groups 1 and 2 (P<0.05). Albendazole plus vitamin A administration showed more efficacy on the improvement of serum retinol and Fe metabolic status. PMID- 26902309 TI - Prospective associations between changes in mental health symptoms and health related quality of life in veterans seeking posttraumatic stress disorder residential treatment. AB - BACKGROUND AND OBJECTIVES: This study examined prospective associations between changes in mental health symptoms (posttraumatic stress disorder [PTSD], depression) and health-related quality of life (physical health, psychological well-being) for veterans with PTSD. DESIGN: This study focused on 139 patients who completed a residential treatment program for PTSD in the Veterans Health Administration. METHODS: Patients completed the veteran-specific, 12-item Medical Outcomes Study Short Form, PTSD Checklist - Military version, and Beck Depression Inventory at pre-treatment, discharge, and a four-month follow-up. When accounting for demographic factors, combat exposure, and baseline scores on the respective outcome variables (e.g. mental health, physical health, PTSD, and depressive symptoms), a series of multivariate analyses were conducted for treatment-related changes in mental and physical health on the outcome measures. RESULTS: Reductions in PTSD symptomatology during the treatment period were prospectively linked with better health-related outcomes at the four-month follow up. In addition, improved physical health and psychological well-being during treatment were each similarly associated with better PTSD and depression outcomes in the months following treatment. CONCLUSIONS: Addressing concerns in mental and physical health might have synergistic effects across both domains, supporting the need for holistic models and integrated health care strategies for treating veterans with PTSD. PMID- 26902312 TI - Thermo-responsive poly(2-isopropyl-2-oxazoline) and tetraphenylethene hybrids for stimuli-responsive photoluminescence control. AB - Poly(2-isopropyl-2-oxazoline) (POx), a typical thermo-responsive polymer, was conjugated with a tetraphenylethene derivative, having aggregation induced emission behavior, towards the thermal control of their fluorescence emission. The poly(2-isopropyl-2-oxazoline)-tetraphenylethene hybrids selectively formed a host-guest complex with gamma-cyclodextrin. The poly(2-isopropyl-2-oxazoline) tetraphenylethene hybrids and its host-guest complex with gamma-cyclodextrin showed opposite on-off switching of fluorescence emission upon temperature change. PMID- 26902311 TI - Hepatic fat content is a determinant of metabolic phenotypes and increased carotid intima-media thickness in obese adults. AB - Individuals with metabolically healthy obesity (MHO) are at relatively low risk for the development of metabolic abnormalities and subclinical atherosclerosis. This study aims to examine whether hepatic fat accumulation determines metabolic phenotype of obesity and associated with subclinical atherosclerosis. A total of 485 obese adults (aged 40-65 years) who received magnetic resonance spectroscopy were divided into metabolically abnormally obesity (MAO) and MHO groups according to metabolic status. MHO individuals had lower levels of intrahepatic triglyceride (IHTG) content and carotid intima-media thickness (CIMT) than MAO individuals. In multivariable linear regression analyses, IHTG content was independently associated with metabolic syndrome components and CIMT. Based on receiver operating characteristic curve analysis, the IHTG content displayed a higher area under the curve (AUC) for detecting the MAO phenotype (AUC = 0.70, 95%CI = 0.65-0.75) and increased CIMT (AUC = 0.60, 95%CI = 0.54-0.66) than BMI, waist circumference, and body fat percent. MHO individuals were 1.9 times (p < 0.001) more likely to have metabolic syndrome per 1 SD change in IHTG content in multivariable-adjusted models. Likewise, the risk for high CIMT increased 29% per 1 SD change in IHTG content [OR (95% CI):1.29(1.01-1.64)]. These findings suggest that hepatic fat is a potential predictor of metabolically unhealthy obesity phenotype and subclinical atherosclerosis. PMID- 26902313 TI - A novel low-power laser-mediated transfer of foreign molecules into cells. AB - Efficiently introducing molecules such as chemical drugs, proteins, or nucleic acids into cells is a central technique in cell and molecular biology, gene therapy and regenerative medicine. The cell membrane is a critical barrier for this purpose. While many approaches exist, some of which are applicable to single cells that researchers specify under microscopy, no reliable and efficient technique has been invented. In this study, cells were cultured on a coverslip that had been coated with carbon by vapor deposition, and a laser beam was focused on a small local spot beneath a single cell under microscopy. The absorbed energy of the laser beam by the carbon made a pore only in the cell membrane that was attached to the carbon coat, which resulted in an efficient introduction. An inexpensive and lower-power laser could be used for this method, and the introduction efficiency was 100% without any loss of cell viability. This new technique will provide a powerful tool not only to research but also to many applied fields. PMID- 26902315 TI - Ellagic acid inhibits non-enzymatic glycation and prevents proteinuria in diabetic rats. AB - The formation of advanced glycation end products (AGEs) is a characteristic feature of diabetic tissues and accumulation of these products has been implicated in the pathogenesis of micro- and macrovascular complications of diabetes including diabetic nephropathy (DN). Compelling evidence suggests that AGEs mediate progressive alteration in the renal architecture and loss of renal function whereas inhibitors of AGEs prevent the progression of experimental DN. We have investigated the potential of ellagic acid (EA), a polyphenol present abundantly in fruits and vegetables, to prevent in vivo accumulation of AGE and to ameliorate renal changes in diabetic rats. Streptozotocin-induced diabetic rats were fed with either 0.2% or 2% of EA in the diet for 12 weeks. Dietary supplementation of EA to diabetic rats prevented the glycation mediated RBC-IgG cross-links and HbA1c accumulation. EA inhibited the accumulation of N carboxymethyl lysine (CML), a predominant AGE in the diabetic kidney. Further, EA also prevented the AGE-mediated loss of expression of podocyte slit diaphragm proteins: nephrin and podocin. By inhibiting CML formation, EA improved renal function in rats as evidenced by urinary albumin and creatinine levels. In conclusion, EA inhibited AGE accumulation in the diabetic rat kidney and ameliorated AGE-mediated pathogenesis of DN. PMID- 26902314 TI - Visualizing Trimming Dependence of Biodistribution and Kinetics with Homo- and Heterogeneous N-Glycoclusters on Fluorescent Albumin. AB - A series of N-glycans, each sequentially trimmed from biantennary sialoglycans, were homo- or heterogeneously clustered efficiently on fluorescent albumin using a method that combined strain-promoted alkyne-azide cyclization and 6pi azaelectrocyclization. Noninvasive in vivo kinetics and dissection analysis revealed, for the first time, a glycan-dependent shift from urinary to gall bladder excretion mediated by sequential trimming of non-reducing end sialic acids. N-glycoalbumins that were trimmed further, in particular, GlcNAc- and hybrid biantennary-terminated congeners, were selectively taken up by sinusoidal endothelial and stellate cells in the liver, which are critical for diagnosis and treatment of liver fibrillation. Our glycocluster strategy can not only reveal the previously unexplored extracellular functions of N-glycan trimming, but will be classified as the newly emerging glycoprobes for diagnostic and therapeutic applications. PMID- 26902317 TI - Finalists are announced for The BMJ Awards 2016. PMID- 26902316 TI - Low-temperature growth of layered molybdenum disulphide with controlled clusters. AB - Layered molybdenum disulphide was grown at a low-temperature of 350 degrees C using chemical vapour deposition by elaborately controlling the cluster size. The molybdenum disulphide grown under various sulphur-reaction-gas to molybdenum precursor partial-pressure ratios were examined. Using spectroscopy and microscopy, the effect of the cluster size on the layered growth was investigated in terms of the morphology, grain size, and impurity incorporation. Triangular single-crystal domains were grown at an optimized sulphur-reaction-gas to molybdenum-precursor partial-pressure ratio. Furthermore, it is proved that the nucleation sites on the silicon-dioxide substrate were related with the grain size. A polycrystalline monolayer with the 100-nm grain size was grown on a nucleation site confined substrate by high-vacuum annealing. In addition, a field effect transistor was fabricated with a MoS2 monolayer and exhibited a mobility and on/off ratio of 0.15 cm(2) V(-1) s(-1) and 10(5), respectively. PMID- 26902318 TI - Increased left atrial pressure in non-heart failure patients with subclinical hypothyroidism and atrial fibrillation. AB - BACKGROUND: The impact of subclinical hypothyroidism on the cardiovascular risk is still debated. We aimed to measure the relationship between subclinical hypothyroidism and the left atrial (LA) pressure. METHODS: The LA pressures and thyroid function were measured in consecutive patients undergoing atrial fibrillation (AF) ablation, who did not have any known heart failure, structural heart disease, or overt thyroid disease. RESULTS: Subclinical hypothyroidism (4.5<= thyroid-stimulating hormone <19.9 mIU/L) was present in 61 (13.0%) of the 471 patients included. More subclinical hypothyroidism patients than euthyroid patients (55.7% vs 40.2%; P=0.04).'euthyroid patients had persistent or long standing persistent AF (55.7% vs 40.2%; P = 0.04). The mean LA pressure (10.9 +/- 4.7 vs 9.1 +/- 4.3 mmHg; P = 0.002) and LA V-wave pressure (17.4 +/- 6.5 vs 14.3 +/- 5.9 mmHg; P < 0.001) were, respectively, higher in the patients with subclinical hypothyroidism than in the euthyroid patients. After an adjustment for potential confounders, the LA pressures remained significantly higher in the subclinical hypothyroidism patients. A multiple logistic regression model showed that subclinical hypothyroidism was independently associated with a mean LA pressure of >18 mmHg (odds ratio 3.94, 95% CI 1.28 11.2; P = 0.02). CONCLUSIONS: Subclinical hypothyroidism may increase the LA pressure in AF patients. PMID- 26902319 TI - A two-photon off-on fluorescence probe for imaging thiols in live cells and tissues. AB - A two-photon (TP) fluorescence imaging probe (Z1) was designed to detect biothiols through a photoinduced electron transfer pathway utilizing N-butyl naphthalimide as the fluorophore and 2,4-dinitrobenzene-sulfonyl as the responsive group, which were linked together by piperazine. The synthesized Z1 displayed high selectivity to biothiols, significant fluorescence off-on properties, and a marked two-photon absorption cross section (delta = 110 GM). Moreover, Z1 showed good biocompatibility and insensitivity toward changes in the biologically relevant pH range (7.2-8.4), which enabled the utilization of Z1 to monitor biothiol levels not only in live cells but also in tissues at depths of 50-250 MUm. PMID- 26902321 TI - Comparison of Strain Rosettes and Digital Image Correlation for Measuring Vertebral Body Strain. AB - Strain gages are commonly used to measure bone strain, but only provide strain at a single location. Digital image correlation (DIC) is an optical technique that provides the displacement, and therefore strain, over an entire region of interest on the bone surface. This study compares vertebral body strains measured using strain gages and DIC. The anterior surfaces of 15 cadaveric porcine vertebrae were prepared with a strain rosette and a speckled paint pattern for DIC. The vertebrae were loaded in compression with a materials testing machine, and two high-resolution cameras were used to image the anterior surface of the bones. The mean noise levels for the strain rosette and DIC were 1 MUepsilon and 24 MUepsilon, respectively. Bland-Altman analysis was used to compare strain from the DIC and rosette (excluding 44% of trials with some evidence of strain rosette failure or debonding); the mean difference +/- 2 standard deviations (SDs) was 108 MUepsilon +/- 702 MUepsilon for the minimum (compressive) principal strain and -53 MUepsilon +/- 332 MUepsilon for the maximum (tensile) principal strain. Although the DIC has higher noise, it avoids the relatively high risk we observed of strain gage debonding. These results can be used to develop guidelines for selecting a method to measure strain on bone. PMID- 26902322 TI - Comment on "Delivering a photosensitive transplatin prodrug to overcome cisplatin drug resistance" by H. Song, W. Li, R. Qi, L. Yan, X. Jing, M. Zheng and H. Xiao, Chem. Commun., 2015, 51, 11493. AB - Consistency of literature results with the transformation of trans diamminedichloridoplatinum(ii) (transplatin) into cis-diammine dichloridoplatinum(ii) (cisplatin) under UVA irradiation claimed in the article recently published in this journal is questioned on the basis of previous and new experimental data. PMID- 26902320 TI - Transient increase of interleukin-1beta after prolonged febrile seizures promotes adult epileptogenesis through long-lasting upregulating endocannabinoid signaling. AB - It remains unclear how infantile febrile seizures (FS) enhance adult seizure susceptibility. Here we showed that the transient increase of interleukin-1beta (IL-1beta) after prolonged FS promoted adult seizure susceptibility, which was blocked by interleukin-1 receptor antagonist (IL-1Ra) within a critical time window. Postnatal administered IL-1beta alone mimicked the effect of FS on adult seizure susceptibility. IL-1R1 knockout mice were not susceptible to adult seizure after prolonged FS or IL-1beta treatment. Prolonged FS or early-life IL 1beta treatment increased the expression of cannabinoid type 1 receptor (CB1R) for over 50 days, which was blocked by IL-1Ra or was absent in IL-1R1 knockout mice. CB1R antagonist, knockdown and endocannabinoid synthesis inhibitor abolished FS or IL-1beta-enhanced seizure susceptibility. Thus, this work identifies a pathogenic role of postnatal IL-1beta/IL-1R1 pathway and subsequent prolonged prominent increase of endocannabinoid signaling in adult seizure susceptibility following prolonged FS, and highlights IL-1R1 as a potential therapeutic target for preventing the development of epilepsy after infantile FS. PMID- 26902323 TI - Is Prostate-Specific Antigen Screening "Proven Ineffective Care"? PMID- 26902324 TI - Clinical Trial Simulations Based on Genetic Stratification and the Natural History of a Functional Outcome Measure in Creutzfeldt-Jakob Disease. AB - IMPORTANCE: A major challenge for drug development in neurodegenerative diseases is that adequately powered efficacy studies with meaningful end points typically require several hundred participants and long durations. Prion diseases represent the archetype of brain diseases caused by protein misfolding, the most common subtype being sporadic Creutzfeldt-Jakob disease (sCJD), a rapidly progressive dementia. There is no well-established trial method in prion disease. OBJECTIVE: To establish a more powerful and meaningful clinical trial method in sCJD. DESIGN, SETTING, AND PARTICIPANTS: A stratified medicine and simulation approach based on a prospective interval-cohort study conducted from October 2008 to June 2014. This study involved 598 participants with probable or definite sCJD followed up over 470 patient-years at a specialist national referral service in the United Kingdom with domiciliary, care home, and hospital patient visits. We fitted linear mixed models to the outcome measurements, and simulated clinical trials involving 10 to 120 patients (no dropouts) with early to moderately advanced prion disease using model parameters to compare the power of various designs. MAIN OUTCOMES AND MEASURES: A total of 2681 assessments were done using a functionally orientated composite end point (Medical Research Council Scale) and associated with clinical investigations (brain magnetic resonance imaging, electroencephalography, and cerebrospinal fluid analysis) and molecular data (prion protein [PrP] gene sequencing, PrPSc type). RESULTS: Of the 598 participants, 273 were men. The PrP gene sequence was significantly associated with decline relative to any other demographic or investigation factors. Patients with sCJD and polymorphic codon 129 genotypes MM, VV, and MV lost 10% of their function in 5.3 (95% CI, 4.2-6.9), 13.2 (95% CI, 10.9-16.6), and 27.8 (95% CI, 21.9-37.8) days, respectively (P < .001). Simulations indicate that an adequately powered (80%; 2-sided alpha = .05) open-label randomized trial using 50% reduction in Medical Research Council Scale decline as the primary outcome could be conducted with only 120 participants assessed every 10 days and only 90 participants assessed daily, providing considerably more power than using survival as the primary outcome. Restricting to VV or MV codon 129 genotypes increased power even further. Alternatively, single-arm intervention studies (half the total sample size) could provide similar power in comparison to the natural history cohort. CONCLUSIONS AND RELEVANCE: Functional end points in neurodegeneration need not require long and very large clinical studies to be adequately powered for efficacy. Patients with sCJD may be an efficient and cost effective group for testing disease-modifying therapeutics. Stratified medicine and natural history cohort approaches may transform the feasibility of clinical trials in orphan diseases. PMID- 26902327 TI - Walking reduces the gap between encoding and sensorimotor alignment effects in spatial updating of described environments. AB - Spatial updating allows people to keep track of the self-to-object relations during movement. Previous studies demonstrated that physical movement enhanced spatial updating in remote environments, but failed to find the same effect in described environments. However, these studies mainly considered rotation as a physical movement, without examining other types of movement, such as walking. We investigated how walking affects spatial updating within described environments. Using the judgement of relative directions task, we compared the effects of imagination of rotation, physical rotation, and walking on spatial updating. Spatial updating was evaluated in terms of accuracy and response times in different perspectives, and by calculating two indexes, namely the encoding and sensorimotor alignment effects. As regards response times, we found that in the imagination of rotation and physical rotation conditions the encoding alignment effect was higher than the sensorimotor alignment effect, while in the walking condition this gap disappeared. We interpreted these results in terms of an enhanced link between allocentric and sensorimotor representations, due to the information acquired through walking. PMID- 26902326 TI - Generation of structurally novel short carotenoids and study of their biological activity. AB - Recent research interest in phytochemicals has consistently driven the efforts in the metabolic engineering field toward microbial production of various carotenoids. In spite of systematic studies, the possibility of using C30 carotenoids as biologically functional compounds has not been explored thus far. Here, we generated 13 novel structures of C30 carotenoids and one C35 carotenoid, including acyclic, monocyclic, and bicyclic structures, through directed evolution and combinatorial biosynthesis, in Escherichia coli. Measurement of radical scavenging activity of various C30 carotenoid structures revealed that acyclic C30 carotenoids showed higher radical scavenging activity than did DL alpha-tocopherol. We could assume high potential biological activity of the novel structures of C30 carotenoids as well, based on the neuronal differentiation activity observed for the monocyclic C30 carotenoid 4,4'-diapotorulene on rat bone marrow mesenchymal stem cells. Our results demonstrate that a series of structurally novel carotenoids possessing biologically beneficial properties can be synthesized in E. coli. PMID- 26902325 TI - Comparative transcriptome and proteome analysis to reveal the biosynthesis of gold nanoparticles in Arabidopsis. AB - A large number of plants have been tested and exploited in search of a green chemistry approach for the fabrication of gold or other precious metal nanomaterials. Despite the potential of plant based methods, very little is known about the underlying biochemical reactions and genes involved in the biotransformation mechanism of AuCl4 into gold nanoparticles (AuNPs). In this research, we thus focused on studying the effect of Au on growth and nanoparticles formation by analyses of transcriptome, proteome and ionome shift in Arabidopsis. Au exposure favored the growth of Arabidopsis seedling and induced formation of nanoparticles in root and shoot, as indicated by optical and hyperspectral imaging. Root transcriptome analysis demonstrated the differential expression of the members of WRKY, MYB and BHLH gene families, which are involved in the Fe and other essential metals homeostasis. The proteome analysis revealed that Glutathione S-transferases were induced in the shoot and suggested its potential role in the biosynthesis AuNPs. This study also demonstrated the role of plant hormone auxin in determining the Au induced root system architecture. This is the first study using an integrated approach to understand the in planta biotransformation of KAuCl4 into AuNPs. PMID- 26902328 TI - Surgical Management of Multifocal Ground-Glass Opacities of the Lung: Correlation of Clinicopathologic and Radiologic Findings. AB - Background We evaluated the clinicopathologic characteristics and oncologic outcome in patients who underwent surgical resection for multifocal ground-glass opacities (GGOs) of the lung. Methods We examined 131 patients who underwent surgical resections for multiple clinical-N0 lung cancers. Multifocal GGOs were defined as tumors showing GGO dominance with a consolidation/tumor ratio (CTR) < 0.5 for all, whereas solid lesions were defined as having at least one tumor that showed CTR >=0.5. Results Multifocal GGOs were found in 53 (40.5%) patients. A significantly large number of GGOs with a median of 3 per patient (range 2-41) was observed in multifocal GGOs (p < 0.0001). A multivariate analysis demonstrated tumor size <= 20 mm (p = 0.0407) and multifocal GGOs (p = 0.0345) were significantly associated with the survival. Regarding surgical managements for multifocal GGOs, the 5-year overall survival (OS) of multiple synchronous or staged limited resection only (n = 26) versus anatomical resection with or without additional limited resection (n = 27) was not significantly different (100% and 91.9%, p = 0.2287). The total number of resected multifocal GGOs was 278, most of which revealed adenocarcinoma or precancerous lesions. Unresected or new GGOs developed in 19 (35.8%) patients, all of which remained pure-GGO of < 10 mm in size without any interventions. The 5-year OS of multifocal GGOs and solid lesions were 94.4% and 80.6% (p = 0.0096), with a median follow-up time of 60 months. Conclusion Surgical interventions combined with limited surgery or adequate follow-up management based on the findings on thin-section CT could provide acceptable oncologic outcomes for multifocal GGOs. PMID- 26902329 TI - Nocardioides ginkgobilobae sp. nov., an endophytic actinobacterium isolated from the root of the living fossil Ginkgo biloba L. AB - A Gram-stain-positive, aerobic and yellow actinobacterial strain, designated SYP A7303T, was isolated from the root of Ginkgo biloba L. Phylogenetic analyses based on 16S rRNA gene sequences indicated that strain SYP-A7303T belongs to the genus Nocardioides. The 16S rRNA gene sequence of strain SYP-A7303T showed highest similarity to Nocardioides marinus CL-DD14T ( = JCM 15615T) (98.3 %) and Nocardioides aquiterrae GW-9T ( = JCM 11813T) (97.1 %), and less than 96.9 % to the type strains of other species of the genus Nocardioides. Strain SYP-A7303T grew optimally at 28 degrees C, pH 7.0 and in the absence of NaCl. It contained ll-2,6-diaminopimelic acid in the cell-wall peptidoglycan, with mannose, ribose, rhamnose, glucose and galactose as whole-cell sugars. The polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol and an unknown lipid. The menaquinone was MK-8(H4) and the predominant cellular fatty acids were iso-C16 : 0, C18 : 1omega9c and C17 : 1omega8c. The DNA G+C content was 72 mol%. Mean DNA-DNA relatedness values between strain SYP-A7303T and the closely related strains N. marinus JCM 15615T and N. aquiterrae JCM 11813T were 62.5 +/- 2.4 and 56.5 +/- 3.5 %, respectively. Based on the morphological, physiological, biochemical and chemotaxonomic characteristics presented in this study, strain SYP-A7303T represents a novel species of the genus Nocardioides, for which the name Nocardioides ginkgobilobae sp. nov. is proposed. The type strain is SYP-A7303T ( = DSM 100492T = KCTC 39594T). PMID- 26902331 TI - Corrigendum: Magnetization Reversal by Out-of-plane Voltage in BiFeO3-based Multiferroic Heterostructures. PMID- 26902330 TI - Statins Improve Long Term Patency of Arteriovenous Fistula for Hemodialysis. AB - The protective effects of statins against stenosis for permanent hemodialysis access have been repeatedly demonstrated in animal studies, but remain controversial in human studies. This study aims to evaluate the association between statin use and permanent hemodialysis access patency using a nationwide hemodialysis cohort. A total of 9862 pairs of statin users and non-users, matched by age and gender, were selected for investigation from 75404 new hemodialysis patients during 2000-2008. The effect of statins on permanent hemodialysis access patency was evaluated using Cox proportional hazards models. Compared with non users, statin users had an overall 18% risk reduction in the composite endpoint in which angioplasty and recreation were combined (adjusted hazard ratio = 0.82 [95%CI, 0.78-0.87]) and 21% in recreation of permanent hemodialysis access (adjusted hazard ratio = 0.79 [95%CI, 0.69-0.80]). Specifically, the protective effect was found for arteriovenous fistula (adjusted hazard ratio = 0.78[95% CI, 0.73-0.82] for composite endpoint and 0.74 [95% CI, 0.69-0.80] for vascular recreation), but not for arteriovenous grafts (adjusted hazard ratio = 1.10 [95% CI, 0.98-1.24] and 0.94 [95% CI, 0.83-1.07]). Statins possess a protective effect for arteriovenous fistula against the recreation of permanent hemodialysis access. The results provide a pharmaco-epidemiologic link between basic research and clinical evidence. PMID- 26902332 TI - Tailoring the chiral magnetic interaction between two individual atoms. AB - Chiral magnets are a promising route towards dense magnetic storage technology due to their inherent nano-scale dimensions and energy efficient properties. Engineering chiral magnets requires atomic-level control of the magnetic exchange interactions, including the Dzyaloshinskii-Moriya interaction, which defines a rotational sense for the magnetization of two coupled magnetic moments. Here we show that the indirect conduction electron-mediated Dzyaloshinskii-Moriya interaction between two individual magnetic atoms on a metallic surface can be manipulated by changing the interatomic distance with the tip of a scanning tunnelling microscope. We quantify this interaction by comparing our measurements to a quantum magnetic model and ab-initio calculations yielding a map of the chiral ground states of pairs of atoms depending on the interatomic separation. The map enables tailoring the chirality of the magnetization in dilute atomic scale magnets. PMID- 26902333 TI - Assessment of the accuracy of estimation of gestational age in cattle from placentome size using inverse regression. AB - AIMS: To assess, in dairy cows between 60-160 days of gestation, whether the agreement between actual gestational age and that predicted by placentome size could be improved by using individual placentome measurements rather than a single average, and to identify how increasing the number of placentomes measured improved the prediction. METHODS: Data were obtained from 58 cows examined using transrectal ultrasonography every 10 days between 60-130 days, and every 15 days between 130-160 days of gestation. For each cow, four to six placentomes in each of the pregnant and non-pregnant horns were examined from the region of the uterus near to the cervix. A mixed-effects model, which included cow as a random effect, and a simple linear regression which ignored within-cow correlation, were fitted to the data. Inverse regression was used to compare the 95% prediction bands obtained for estimating gestational age using the means of three, five or eight placentome measurements. RESULTS: The fit of the mixed effects model was better than a simple linear regression (p<0.001) but the fitted lines from the two models were very similar. Using the simple regression model, for a mean placentome length of 15 mm estimated gestational age was 100 days, with 95% CI of 68-131 days for measurement of three placentomes, and 80-120 days for eight placentomes. CONCLUSIONS: The agreement between placentome size and gestational age was improved by increasing the number of placentomes measured. Direct comparison of these CI with those for other published fetal measures was not possible as similar prediction bands have not previously been calculated for fetal measures; however one study reported a residual SD which had been calculated using size measurements as the predictor variable and age as the response variable. Using these data 95% CI were calculated to be +/-9 days for crown-rump length and +/-25 days for uterine diameter. These are likely to be an underestimate of the true CI and do not take account of the increase in variance of the difference between predicted and actual gestational age as gestational age increases. CLINICAL RELEVANCE: Placentome measurement may be useful for estimating fetal age in late gestation. Further research is required to better establish the agreement between gestational age and the fetal measurements which are currently used to estimate fetal age. PMID- 26902334 TI - Prostate cancer: Multilayered mutation analysis indicates divergent clonal evolution. PMID- 26902338 TI - Genetics: Selfish spermatogonia. PMID- 26902340 TI - Prostate Cancer: Box clever--YB-1 has a role in CRPC. PMID- 26902337 TI - Current use of PSMA-PET in prostate cancer management. AB - Currently, the findings of imaging procedures used for detection or staging of prostate cancer depend on morphology of lymph nodes or bone metabolism and do not always meet diagnostic needs. Prostate-specific membrane antigen (PSMA), a transmembrane protein that has considerable overexpression on most prostate cancer cells, has gained increasing interest as a target molecule for imaging. To date, several small compounds for labelling PSMA have been developed and are currently being investigated as imaging probes for PET with the (68)Ga-labelled PSMA inhibitor Glu-NH-CO-NH-Lys(Ahx)-HBED-CC being the most widely studied agent. (68)Ga-PSMA-PET imaging in combination with multiparametric MRI (mpMRI) might provide additional molecular information on cancer localization within the prostate. In patients with primary prostate cancer of intermediate-risk to high risk, PSMA-based imaging has been reported to improve detection of metastatic disease compared with CT or mpMRI, rendering additional cross-sectional imaging or bone scintigraphy unnecessary. Furthermore, in patients with biochemically recurrent prostate cancer, use of (68)Ga-PSMA-PET imaging has been shown to increase detection of metastatic sites, even at low serum PSA values, compared with conventional imaging or PET examination with different tracers. Thus, although current knowledge is still limited and derived mostly from retrospective series, PSMA-based imaging holds great promise to improve prostate cancer management. PMID- 26902342 TI - Prostate cancer: Increased dementia risk following androgen deprivation therapy? PMID- 26902343 TI - Anatomic characterization of prelemniscal radiations by probabilistic tractography: implications in Parkinson's disease. AB - To characterize the anatomical connectivity of the prelemniscal radiations (Raprl), a white matter region within the posterior subthalamic area (PSA) that is an effective neurosurgical target for treating motor symptoms of Parkinson's disease (PD). Diffusion-weighted images were acquired from twelve healthy subjects using a 3T scanner. Constrained spherical deconvolution, a method that allows the distinction of crossing fibers within a voxel, was used to compute track-density images with sufficient resolution to accurately delineate distinct PSA regions and probabilistic tractography of Raprl in both hemispheres. Raprl connectivity was reproducible across all subjects and showed fibers traversing through this region towards primary and supplementary motor cortices, the orbitofrontal cortex, ventrolateral thalamus, and the globus pallidus, cerebellum and dorsal brainstem. All brain regions reached by Raprl fibers are part of motor circuits involved in the pathophysiology of PD; while these fiber systems converge at the level of the PSA, they can be spatially segregated. Fibers of distinct and specific motor control networks are identified within Raprl. The description of this anatomical crossroad suggests that, in the future, tractography could allow deep brain stimulation or lesional therapies in white matter targets according to individual patient's symptoms. PMID- 26902344 TI - 'If she is a good woman ...' and 'to be a real man ...': gender, risk and access to HIV services among key populations in Tajikistan. AB - The HIV epidemic continues to grow in Tajikistan, especially among people who inject drugs, sex workers, men who have sex with men and incarcerated populations. Despite their susceptibility to HIV, members of these groups do not always have access to HIV prevention, testing and treatment. The purpose of this study was to identify and understand the gender constraints in accessing HIV services for key populations in Tajikistan. Using focus-group discussions and key informant interviews the assessment team collected information from members of key populations and those who work with them. Several themes emerged from the data, including: low levels of HIV knowledge, gender constraints to condom use and safer drug use, gender constraints limit HIV testing opportunities, gender based violence, stigma and discrimination, and the lack of female spaces in the HIV response. The results of this study show that there are well-defined gender norms in Tajikistan, and these gender norms influence key populations' access to HIV services. Addressing these gender constraints may offer opportunities for more equitable access to HIV services in Tajikistan. PMID- 26902345 TI - Bioconversion of methane to lactate by an obligate methanotrophic bacterium. AB - Methane is the second most abundant greenhouse gas (GHG), with nearly 60% of emissions derived from anthropogenic sources. Microbial conversion of methane to fuels and value-added chemicals offers a means to reduce GHG emissions, while also valorizing this otherwise squandered high-volume, high-energy gas. However, to date, advances in methane biocatalysis have been constrained by the low productivity and limited genetic tractability of natural methane-consuming microbes. Here, leveraging recent identification of a novel, tractable methanotrophic bacterium, Methylomicrobium buryatense, we demonstrate microbial biocatalysis of methane to lactate, an industrial platform chemical. Heterologous overexpression of a Lactobacillus helveticus L-lactate dehydrogenase in M. buryatense resulted in an initial titer of 0.06 g lactate/L from methane. Cultivation in a 5 L continuously stirred tank bioreactor enabled production of 0.8 g lactate/L, representing a 13-fold improvement compared to the initial titer. The yields (0.05 g lactate/g methane) and productivity (0.008 g lactate/L/h) indicate the need and opportunity for future strain improvement. Additionally, real-time analysis of methane utilization implicated gas-to-liquid transfer and/or microbial methane consumption as process limitations. This work opens the door to develop an array of methanotrophic bacterial strain-engineering strategies currently employed for biocatalytic sugar upgrading to "green" chemicals and fuels. PMID- 26902346 TI - Effects of NO Donors and Inhibitors of NO Synthase and Guanylate Cyclase on the Acquisition of a Conditioned Defense Food Aversion Response in Edible Snails. AB - Experiments on edible snails revealed that NO synthase blockade with a nonspecific neuronal NO synthase inhibitor L-NAME before defense food aversion conditioning is followed by a decrease in the rate of learning. Exogenous NO donors, sodium nitroprusside and dinitrosyl iron complex, were shown to improve learning. Chronic administration of a specific soluble guanylate cyclase inhibitor ODQ also increased the rate of learning. Our results indicate that NO has a modulatory effect on the formation of a conditioned response in this type of learning. PMID- 26902347 TI - Maintenance of the Cardiovascular Function in a Deeply Cooled Homeothermic Organism by Physiological Methods without External Rewarming. AB - Gradual cooling of homeothermic organisms is followed by slowing and arrest of breathing and heart contractions. During deep cooling, even relatively slight artificial ventilation decreases the lower temperature limit of life (by 4.5-5 degrees C) and provides minimum oxygen supply to the heart and whole body. This allows us to restore cardiovascular function and prevent animal death after lethal cooling without eternal warming. PMID- 26902348 TI - A Hardware-and-Software System for Experimental Studies of the Acoustic Startle Response in Laboratory Rodents. AB - We developed and tested a novel hardware-and-software system for recording the amplitude of the acoustic startle response in rodents. In our experiments, the baseline indexes of acoustic startle response in laboratory rats and pre stimulation inhibition under the standard delivery of acoustic stimulation were similar to those evaluated by other investigators on foreign devices. The proposed system is relatively cheap and provides the possibility of performing experiments on freely moving specimens. It should be emphasized that the results of studies can be processed with free-access software. PMID- 26902349 TI - Pathogenetic Evaluation of Dysfunction in the Erythron System of Experimental Animals during Modeling of Iron Deficiency Anemia in the Gestation Period. AB - We studied the dynamics of erythropoiesis in CBA mice during gestation against the background of treatment with iron-binding drug. The mechanisms of suppression of the bone marrow erythroid stem were evaluated. Administration of deferoxamine in a dose of 1 g/kg induced hypoplasia of the erythroid hemopoietic lineage. Suppression of bone marrow erythropoiesis manifested in a decrease of hemoglobin concentration and counts of reticulocytes, erythrocytes, and erythrokaryocytes. These changes were accompanied by a decrease in functional activity of erythropoietic precursors and secretion of erythropoietically active humoral factors by bone marrow myelokaryocytes. These data indicate that deferoxamine can be used for modeling of iron defi ciency anemia in pregnancy. PMID- 26902350 TI - Neuroprotective Effects of Peptides during Ischemic Preconditioning. AB - Experiments on rats showed that neurospecific protein preparations reduce the severity of neurological deficit, restore the structure of individual behavior of the animals with different hypoxia tolerance, and exert antioxidant action during chronic ischemic damage to the brain unfolding during the early and late phases of ischemic preconditioning. PMID- 26902351 TI - Effect of Delta Sleep-Inducing Peptide on Functional State of Hepatocytes in Rats During Restraint Stress. AB - We studied the effect of delta sleep-inducing peptide (40, 120, and 360 MUg/kg intraperitoneally, 1 h before the experiment) on free radical oxidation in the liver, aminotransferase activity, and total serum protein content in male Wistar rats during restraint stress. Treatment with the peptide in a dose of 40 MUg/kg increased catalase and superoxide dismutase (SOD) activities and malonic dialdehyde (MDA) concentration in the liver homogenate of animals subjected to acute stress. No significant changes were found after administration of this peptide in other doses. Under conditions of chronic stress, the peptide in a dose of 40 MUg/kg caused the most pronounced effect. Catalase and SOD activities and MDA concentration decreased, while aminotransferase activity and protein content remained unchanged under these conditions. Administration of the peptide in a dose of 120 MUg/kg was accompanied by a decrease in SOD activity and MDA concentration, increase in total protein content, and reduction of AST activity. Increasing the peptide dose to 360 MUg/kg abolished its effects. PMID- 26902352 TI - Psychotropic Activity of New Fluorinated Derivatives of Tetrahydrocarbasoles. AB - Psychotropic properties of CA-7043* and CA-7050*, new fluorinated derivatives of tetrahydrocarbasoles, were examined on outbred CD1 mice and transgenic 5*FAD mice with Alzheimer disease. Both agents exerted cognitive-stimulating and anxiolytic effects in a dose of 5 mg/kg. In the new cage test, they retarded extinction of orientation and exploratory behavior. CA-7043* produced an anxiolytic effect on CD1 mice assessed in the open-field test and exerted cognitive-stimulating action in the new location test. In the same tests, CA-7050* demonstrated the cognitive stimulating and anxiolytic effects on transgenic 5*FAD mice. PMID- 26902353 TI - Binding Potency of Heparin Immobilized on Activated Charcoal for DNA Antibodies. AB - In vitro experiments showed that heparin adsorbed on activated charcoal can bind antibodies raised against native and single-stranded DNA in a diluted sera pool with a high level of these DNA. Thus, heparin used as anticoagulant during hemosorption procedure can demonstrate supplementary therapeutic activity resulting from its interaction with various agents involved in acute and chronic inflammatory reactions such as DNA- and RNA-binding substances, proinflammatory cytokines, complement components, growth factors, etc. Research and development of heparin-containing carbonic adsorbents for the therapy of numerous inflammatory and autoimmune diseases seems to be a promising avenue in hematology. PMID- 26902354 TI - The Mechanism of Adaptation of Breast Cancer Cells to Hypoxia: Role of AMPK/mTOR Signaling Pathway. AB - We studied the mechanisms of adaptation of human breast cancer cells MCF-7 to hypoxia and analyzed the role of AMPK/mTOR signaling pathway in the maintenance of cell proliferation under hypoxic conditions. It was found that long-term culturing (30 days or more) of MCF-7 cells under hypoxic conditions induced their partial adaptation to hypoxia. Cell adaptation to hypoxia was associated with attenuation of hypoxia-dependent AMPK induction with simultaneous constitutive activation of mTOR and Akt. These findings suggest that these proteins can be promising targets for targeted therapy of tumors developing under hypoxic conditions. PMID- 26902355 TI - Dynamic Structure of Proteoglycans/Glycosaminoglycans in the Lungs of Mice with Chronic Granulomatous Inflammation. AB - Structure of proteoglycans in the lungs and total glycosaminoglycan content in blood serum were studied on mouse model of BCG-induced granulomatous inflammation in mice (without destructive processes in the lung parenchyma and granulomas). The maximum level of sulfated glycosaminoglycans in the lungs was detected on postinfection day 30 and was related to their involvement in initiation granulomogenesis and development of granulomas. The maximum level of total glycosaminoglycans in mouse serum on postinfection day 90 coincided with minimum level of sulfated glycosaminoglycans in the lungs. This blood/lungs ratio of glycosaminoglycans can be related to the prevalence of low-molecular-weight hyaluronan fragments promoting inflammation and fibrosis in the lungs observed at the end of the experiment (postinfection day 180). PMID- 26902356 TI - Response of Hematopoietic Stem and Progenitor Cells to Reserpine in C57Bl/6 Mice. AB - We studied the response of hematopoietic stem cells and progenitor cells to sympatholytic reserpine in intact C57Bl/6 mice and in animals with cyclophosphamide-induced leukopenia. The count of long-term hematopoietic stem cells (Lin(-)Sca-1(+)c-kit(+)CD34(-)) in the bone marrow of healthy mice increased in 7 min after reserpine injection and remained elevated in 2 h in parallel with elevated content of short-term stem (Lin(-)Sca-1(+)c-kit(+)CD34(+)) and progenitor (Lin(-)Sca-1(+)c-kit(+)) cells. Reserpine produced no effect on recruitment of hematopoietic stem and progenitor cells into the peripheral blood, but increased the serum level of granulocyte CSF and increased the count of metamyelocytes and neutrophilic granulocytes in the blood (in 2 h postinjection). Transplantation of bone marrow hematopoietic stem and progenitor cells from reserpine-treated donor C57Bl/6 mice to recipient CBA mice with 5-fluorouracil induced leukopenia accelerated regeneration of the granulocytic lineage cells in leukemic mice. In cyclophosphamide-treated C57Bl/6 mice, reserpine reduced the level of short-term hematopoietic stem cells and increased the count of progenitor hematopoietic cells in the bone marrow in parallel with recruitment of the progenitors into the peripheral blood. PMID- 26902357 TI - Sirt1 Regulates p53 Stability and Expression of Its Target S100B during Long-Term Potentiation in Rat Hippocampus. AB - Induction of long-term potentiation in rat hippocampus was followed by short-term activation of transcription factor p53 and its subsequent degradation. We studied the effects of EX-527 (inhibitor of deacetylase Sirt1, a negative regulator of p53) and pifi thrin-beta (inhibitor of p53-dependent transcription) on the levels of p53 protein and mRNA of its target gene S100B during long-term potentiation. Pifi thrin-beta limited the increase in S100B mRNA content after tetanization, which confi rmed signifi cant contribution of p53 in the regulation of S100B during long-term potentiation. EX-527 completely prevented p53 degradation and increased S100B expression induced by tetanization. Thus, Str1 regulates stability of p53 and expression of its target gene S100B in rat hippocampus during long-term potentiation. PMID- 26902358 TI - Assessment of Expression of Genes Coding GABAA Receptors during Chronic and Acute Intoxication of Laboratory Rats with Ethanol. AB - Expression of genes encoding the individual subunits of ionotropic GABAA receptor was assessed after acute and chronic intoxication of rats with ethanol. The chronic 1-month-long exposure to ethanol signifi cantly decreased (by 38%) expression of Gabrb1 gene in the hippocampus. Acute exposure to ethanol elevated expression of genes Gabrb1 (by 1.7 times), Gabra1 (by 3.8 times), and Gabra4 (by 6.5 times), although it diminished expression of Gabra2 gene by 1.4 times. In preliminarily alcoholized rats, acute intoxication with ethanol enhanced expression of genes Gabrb1 and Gabra5 by 1.7 and 8.7 times, respectively. There was neither acute nor chronic effect of ethanol on expression of gene Gabra3. PMID- 26902359 TI - Isolation of Multipotent Mesenchymal Stromal Cells from Cryopreserved Human Umbilical Cord Tissue. AB - Umbilical cord stroma is an easily available, convenient, and promising source of multipotent mesenchymal stromal cells for regenerative medicine. Cryogenic storage of umbilical cord tissue provides more possibilities for further isolation of multipotent mesenchymal stromal cells for autologous transplantation or scientific purposes. Here we developed a protocol for preparation of the whole umbilical cord tissue for cryogenic storage that in combination with the previously described modified method of isolation of multipotent mesenchymal stromal cells allowed us to isolate cells with high proliferative potential, typical phenotype, and preserved differentiation potencies. PMID- 26902360 TI - Anticonvulsant Effects of Combined Treatment with Citicoline and Valproate on the Model of Acute Generalized Convulsions Induced by Pentylenetetrazole in Wistar Rats. AB - We studied anticonvulsant effects of combined treatment with citicoline, a nootropic substance with neuroregenerative and neuroprotective activities, and valproate, an antiepileptic agent widely used in the treatment of epilepsy, on the model of pentylenetetrazole-induced (75 mg/kg, intraperitoneally) acute generalized convulsions in male Wistar rats. Combined treatment with citicoline and valproate in minimum effective doses (70 and 300 mg/kg, respectively) potentiated the anticonvulsant properties of both agents. PMID- 26902361 TI - Efficiency of Cell Therapy in Liver Cirrhosis. AB - We studied safety and clinical efficacy of transplantation of autologous bone marrow cell in complex therapy of 158 patients with chronic hepatitis and cirrhosis of the liver. The efficiency of cell therapy was assessed in 12 months after single injection of the cells. The positive response (alleviation of liver cirrhosis or stabilization of the pathological process) was observed in 70% cases. The efficacy of therapy correlated with the severity and etiology of the disease and was maximum in patients with Child-Pugh class A (in 82.5% cases) and class B liver cirrhosis (in 79% cases); in patients with class C liver cirrhosis, the positive response was achieved in 42.5% cases. In 39 patients, ultrasonic examination performed in 3 years after transplantation revealed no focal lesions or ectopic ossification foci. PMID- 26902362 TI - Antitumor Activity of Rat Mesenchymal Stem Cells during Direct or Indirect Co Culturing with C6 Glioma Cells. AB - The tumor-suppressive effect of rat mesenchymal stem cells against low differentiated rat C6 glioma cells during their direct and indirect co-culturing and during culturing of C6 glioma cells in the medium conditioned by mesenchymal stem cells was studied in an in vitro experiment. The most pronounced antitumor activity of mesenchymal stem cells was observed during direct co-culturing with C6 glioma cells. The number of live C6 glioma cells during indirect co-culturing and during culturing in conditioned medium was slightly higher than during direct co-culturing, but significantly differed from the control (C6 glioma cells cultured in medium conditioned by C6 glioma cells). The cytotoxic effect of medium conditioned by mesenchymal stem cells was not related to medium depletion by glioma cells during their growth. The medium conditioned by other "non-stem" cells (rat astrocytes and fibroblasts) produced no tumor-suppressive effect. Rat mesenchymal stem cells, similar to rat C6 glioma cells express connexin 43, the main astroglial gap junction protein. During co-culturing, mesenchymal stem cells and glioma C6 cells formed functionally active gap junctions. Gap junction blockade with connexon inhibitor carbenoxolone attenuated the antitumor effect observed during direct co-culturing of C6 glioma cells and mesenchymal stem cells to the level produced by conditioned medium. Cell-cell signaling mediated by gap junctions can be a mechanism of the tumor-suppressive effect of mesenchymal stem cells against C6 glioma cells. This phenomenon can be used for the development of new methods of cell therapy for high-grade malignant gliomas. PMID- 26902363 TI - Comparative Analysis of the Proliferative Potential of Human Mesenchymal Stromal Cells from Extraembryonic Organs, Endometrium, and Adipose Tissue. AB - Proliferative activity of mesenchymal stromal cells isolated from five sources (chorionic villi, Wharton's jelly, amnion, endometrium, and adipose tissue) was compared by flow cytometry and real-time PCR (by the content of mRNA of genes encoding of cell cycle regulators). Mesenchymal stromal cells derived from the endometrium demonstrated maximum stability and high proliferative potential. PMID- 26902364 TI - A pathway for spatial memory encoding. AB - The medial prefrontal cortex has been shown to play a role for rodents in successful completion of tasks that require spatial memory, but the pathways responsible for the transmission of spatial information to the mPFC, and the nature and timing of such information, are unknown. Recently, Spellman, Rigotti, Ahmari, Fusi, Gogos, and Gordon (Nature, 522, 309-314, 2015) addressed these questions in an eloquent and ingenious series of experiments, which we review in the broader context of the neurobiology of spatial memory. PMID- 26902365 TI - Health Promotion in the Community: Impact of Faith-Based Lay Health Educators in Urban Neighborhoods. AB - Promoting wellness and providing reliable health information in the community present serious challenges. Lay health educators, also known as community health workers, may offer a cost-effective solution to such challenges. This is a retrospective observational study of graduates from the Lay Health Educator Program (LHEP) at Johns Hopkins Bayview Medical Center from 2013 to 2014. Students were enrolled from the surrounding community congregations and from the hospital's accredited clinical pastoral education program. There were 50 events implemented by the lay health educators during the 2014-2015 time period, reaching a total of 2004 individuals. The mean time from date of graduation from the LHEP to implementation of their first health promotional event was 196 +/- 76 days. A significant number of lay health educators implemented events within the first year after completing their training. Ongoing monitoring of their community activity and the clinical impact of their efforts should be a priority for future studies. PMID- 26902367 TI - Laparoscopic double-stapled colorectal anastomosis without "dog-ears". PMID- 26902366 TI - A person-centered intervention targeting the psychosocial needs of gynecological cancer survivors: a randomized clinical trial. AB - PURPOSE: We investigated the effect of a person-centered intervention consisting of two to four nurse-led conversations using guided self-determination tailored to gynecologic cancer (GSD-GYN-C) on gynecological cancer survivors' quality of life (QOL), impact of cancer, distress, anxiety, depression, self-esteem, and self-reported ability to monitor and respond to symptoms of recurrence. METHODS: We randomly assigned 165 gynecological cancer survivors to usual care (UC) plus GSD-GYN-C or UC alone. Self-reported QOL-cancer survivor (QOL-CS) total score and subscale scores on physical, psychological, social, and spiritual well-being were assessed before randomization and at 3 and 9 months after randomization using t tests. Bonferroni and Pipper corrections were applied for multiple testing adjustments. RESULTS: At 9 months, the GSD-GYN-C plus UC group scored significantly higher on the QOL-CS total scale (P = 0.02) and on the QOL-CS physical well-being subscale (P = 0.01), compared to women receiving UC alone. After adjusting for baseline scores, only the difference in the physical well being subscale was statistically significant. No other measured outcomes differed between the intervention and control groups after baseline adjustment. CONCLUSION: We observed higher physical well-being 9 months after randomization in the GSD-GYN-C group, as compared to women receiving usual care. IMPLICATIONS FOR CANCER SURVIVORS: The results suggest that the person-centered intervention GSD-GYN-C may improve physical well-being in gynecological cancer survivors. However, further testing is needed. PMID- 26902368 TI - Rectal atresia and anal stenosis: the difference in the operative technique for these two distinct congenital anorectal malformations. AB - Rectal atresia and anal stenosis are rare forms of anorectal malformations. The aim of the definitive surgical repair in such cases is to preserve the anal canal, the dentate line, and the sphincter complex. We present a case of rectal atresia and anal stenosis to demonstrate the differences in the operative repair. The techniques described leave the anterior wall of the very distal anal canal untouched in both rectal stenosis and anal atresia; however, the dissection of the rectum differs. The atretic rectum in rectal atresia is mobilized and sutured to the anal canal circumferentially. In anal stenosis, the posterior rectum is mobilized in the form of rectal advancement, and the posterior 180 degrees is anastomosed directly to the skin (as in a standard PSARP) with preservation of the anal canal as the anterior 180 degrees of the final anoplasty. These patients have an excellent prognosis for bowel control and fecal continence, and therefore, complete mobilization and resection of the anal canal must be avoided. PMID- 26902370 TI - [(11)C]TASP457, a novel PET ligand for histamine H3 receptors in human brain. AB - PURPOSE: The histamine H3 receptors are presynaptic neuroreceptors that inhibit the release of histamine and other neurotransmitters. The receptors are considered a drug target for sleep disorders and neuropsychiatric disorders with cognitive decline. We developed a novel PET ligand for the H3 receptors, [(11)C]TASP0410457 ([(11)C]TASP457), with high affinity, selectivity and favorable kinetic properties in the monkey, and evaluated its kinetics and radiation safety profile for quantifying the H3 receptors in human brain. METHODS: Ten healthy men were scanned for 120 min with a PET scanner for brain quantification and three healthy men were scanned for radiation dosimetry after injection of 386 +/- 6.2 MBq and 190 +/- 7.5 MBq of [(11)C]TASP457, respectively. For brain quantification, arterial blood sampling and metabolite analysis were performed using high-performance liquid chromatography. Distribution volumes (V T) in brain regions were determined by compartment and graphical analyses using the Logan plot and Ichise multilinear analysis (MA1). For dosimetry, radiation absorbed doses were estimated using the Medical Internal Radiation Dose scheme. RESULTS: [(11)C]TASP457 PET showed high uptake (standardized uptake values in the range of about 3 - 6) in the brain and fast washout in cortical regions and slow washout in the pallidum. The two-tissue compartment model and graphical analyses estimated V T with excellent identification using 60-min scan data (about 16 mL/cm(3) in the pallidum, 9 - 14 in the basal ganglia, 6 - 9 in cortical regions, and 5 in the pons), which represents the known distribution of histamine H3 receptors. For parametric imaging, MA1 is recommended because of minimal underestimation with small intersubject variability. The organs with the highest radiation doses were the pancreas, kidneys, and liver. The effective dose delivered by [(11)C]TASP457 was 6.9 MUSv/MBq. CONCLUSION: [(11)C]TASP457 is a useful novel PET ligand for the investigation of the density of histamine H3 receptors in human brain. PMID- 26902371 TI - Combination of baseline metabolic tumour volume and early response on PET/CT improves progression-free survival prediction in DLBCL. AB - BACKGROUND: The study objectives were to assess the prognostic value of quantitative PET and to test whether combining baseline metabolic tumour burden with early PET response could improve predictive power in DLBCL. METHODS: A total of 147 patients with DLBCL underwent FDG-PET/CT scans before and after two cycles of RCHOP. Quantitative parameters including metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were measured, as well as the percentage change in these parameters. Cox regression analysis was used to test the relationship between progression-free survival (PFS) and the study variables. Receiver operator characteristics (ROC) analysis determined the optimal cut-off for quantitative variables, and Kaplan-Meier survival analysis was performed. RESULTS: The median follow-up was 3.8 years. As MTV and TLG measures correlated strongly, only MTV measures were used for multivariate analysis (MVA). Baseline MTV (MTV-0) was the only statistically significant predictor of PFS on MVA. The optimal cut-off for MTV-0 was 396 cm(3). A model combing MTV-0 and Deauville score (DS) separated the population into three distinct prognostic groups: good (MTV-0 < 400; 5-year PFS > 90 %), intermediate (MTV-0 >= 400+ DS1-3; 5-year PFS 58.5 %) and poor (MTV-0 >= 400+ DS4-5; 5-year PFS 29.7 %) CONCLUSIONS: MTV-0 is an important prognostic factor in DLBCL. Combining MTV-0 and early PET/CT response improves the predictive power of interim PET and defines a poor prognosis group in whom most of the events occur. PMID- 26902369 TI - [Hypercapnic respiratory failure. Pathophysiology, indications for mechanical ventilation and management]. AB - BACKGROUND: Acute hypercapnic respiratory failure is mostly seen in patients with chronic obstructive pulmonary disease (COPD) and obesity hypoventilation syndrome (OHS). Depending on the underlying cause it may be associated with hypoxemic respiratory failure and places high demands on mechanical ventilation. OBJECTIVE: Presentation of the current knowledge on indications and management of mechanical ventilation in patients with hypercapnic respiratory failure. MATERIAL AND METHODS: Review of the literature. RESULTS: Important by the selection of mechanical ventilation procedures is recognition of the predominant pathophysiological component. In hypercapnic respiratory failure with a pH < 7.35 non-invasive ventilation (NIV) is primarily indicated unless there are contraindications. In patients with severe respiratory acidosis NIV requires a skilled and experienced team and close monitoring in order to perceive a failure of NIV. In acute exacerbation of COPD ventilator settings need a long expiration and short inspiration time to avoid further hyperinflation and an increase in intrinsic positive end-expiratory pressure (PEEP). Ventilation must be adapted to the pathophysiological situation in patients with OHS or overlap syndrome. If severe respiratory acidosis and hypercapnia cannot be managed by mechanical ventilation therapy alone extracorporeal venous CO2 removal may be necessary. Reports on this approach in awake patients are available. CONCLUSION: The use of NIV is the predominant treatment in patients with hypercapnic respiratory failure but close monitoring is necessary in order not to miss the indications for intubation and invasive ventilation. Methods of extracorporeal CO2 removal especially in awake patients need further evaluation. PMID- 26902373 TI - In Vitro-In Vivo Evaluation of Novel Co-spray Dried Rifampicin Phospholipid Lipospheres for Oral Delivery. AB - The objective of this study comprises of developing novel co-spray dried rifampicin phospholipid lipospheres (SDRPL) to investigate its influence on rifampicin solubility and oral bioavailability. Solid-state techniques were employed to characterize the liposphere formulation. SDRPL solubility was determined in distilled water. BACTEC 460TB System was employed to evaluate SDRPL antimycobacterial activity. The oral bioavailability of the lipospheres was evaluated in Sprague Dawley rats. Lipospheres exhibited amorphous, smooth spherical morphology with a significant increase (p < 0.001) in solubility of SDRPL (2:1), 350.9 +/- 23 versus 105.1 +/- 12 MUg/ml and SDRPL (1:1) 306.4 +/- 20 versus 105.1 +/- 12 MUg/ml in comparison to rifampicin (RMP). SDRPL exhibited enhanced activity against Mycobacterium tuberculosis, H37Rv strain, with over twofolds less minimum inhibitory concentration (MIC) than the free drug. Lipospheres exhibited higher peak plasma concentration (109.92 +/- 25 versus 54.31 +/- 18 MUg/ml), faster T max (two versus four hours), and enhanced area under the curve (AUC0-infinity) (406.92 +/- 18 versus 147.72 +/- 15 MUg h/L) in comparison to pure RMP. Thus, SDRPL represents a promising carrier system exhibiting enhanced antimycobacterial activity and oral bioavailability of rifampicin. PMID- 26902374 TI - Evaluating Choroidal Characteristics in Systemic Sclerosis Using Enhanced Depth Imaging Optical Coherence Tomography. AB - PURPOSE: To evaluate choroidal thickness (CT) and investigate the involvement of choroidal circulation in patients with systemic sclerosis (SSc). METHODS: A total of 120 eyes of 60 SSc patients and 60 eyes of 30 healthy controls were evaluated. CT measurements were performed at the subfoveal region, 1000 um nasal and 1000 um temporal to the fovea, using enhanced depth imaging optical coherence tomography. CT measurements were compared between the patients and controls. RESULTS: The average subfoveal, parafoveal nasal and parafoveal temporal CT were significantly thinner in SSc patients when compared with healthy controls (297.77 +/- 60.8 um vs 339.8 +/- 50.4 um; 267.32 +/- 51.1 um vs 308.65 +/- 49.9 um; 270.63 +/- 46.3 um vs 309.22 +/- 42.4 um, respectively; p<0.001 for all). CONCLUSIONS: Reduced CT in SSc patients supports the hypothesis of widespread vascular injury, including the ocular microcirculation. PMID- 26902372 TI - Decoding three-dimensional reaching movements using electrocorticographic signals in humans. AB - OBJECTIVE: Electrocorticography (ECoG) signals have emerged as a potential control signal for brain-computer interface (BCI) applications due to balancing signal quality and implant invasiveness. While there have been numerous demonstrations in which ECoG signals were used to decode motor movements and to develop BCI systems, the extent of information that can be decoded has been uncertain. Therefore, we sought to determine if ECoG signals could be used to decode kinematics (speed, velocity, and position) of arm movements in 3D space. APPROACH: To investigate this, we designed a 3D center-out reaching task that was performed by five epileptic patients undergoing temporary placement of ECoG arrays. We used the ECoG signals within a hierarchical partial-least squares (PLS) regression model to perform offline prediction of hand speed, velocity, and position. MAIN RESULTS: The hierarchical PLS regression model enabled us to predict hand speed, velocity, and position during 3D reaching movements from held out test sets with accuracies above chance in each patient with mean correlation coefficients between 0.31 and 0.80 for speed, 0.27 and 0.54 for velocity, and 0.22 and 0.57 for position. While beta band power changes were the most significant features within the model used to classify movement and rest, the local motor potential and high gamma band power changes, were the most important features in the prediction of kinematic parameters. SIGNIFICANCE: We believe that this study represents the first demonstration that truly three-dimensional movements can be predicted from ECoG recordings in human patients. Furthermore, this prediction underscores the potential to develop BCI systems with multiple degrees of freedom in human patients using ECoG. PMID- 26902375 TI - Electrogenerated Chemiluminescence Behavior of Au nanoparticles-hybridized Pb (II) metal-organic framework and its application in selective sensing hexavalent chromium. AB - In this work, a novel electrochemiluminescence (ECL) sensor based on Au nanoparticles-hybridized Pb (II)-beta-cyclodextrin (Pb-beta-CD) metal-organic framework for detecting hexavalent chromium (Cr(VI)) was developed. Pb-beta-CD shows excellent ECL behavior and unexpected reducing ability towards Au ions. Au nanoparticles could massively form on the surface of Pb-beta-CD (Au@Pb-beta-CD) without use of any additional reducing agent. In the presence of coreactant K2S2O8, the ECL emission of Pb-beta-CD was enhanced by the formation of Au nanoparticles. Cr(VI) can collisionally quench the ECL behavior of Au@Pb-beta CD/S2O8(2-) system and the detection mechanism was investigated. This ECL sensor is found to have a linear response in the range of 0.01-100 MUM and a low detection limit of 3.43 nM (S/N = 3) under the optimal conditions. These results suggest that metal-organic framework Au@Pb-beta-CD has great potential in extending the application in the ECL field as an efficient luminophore. PMID- 26902376 TI - Novel Index (Hepatic Receptor: IHR) to Evaluate Hepatic Functional Reserve Using (99m)Tc-GSA Scintigraphy. AB - PURPOSE: This study aimed to evaluate the novel index of hepatic receptor (IHR) on the regression analysis derived from time activity curve of the liver for hepatic functional reserve. METHODS: Sixty patients had undergone (99m)Tc galactosyl serum albumin ((99m)Tc-GSA) scintigraphy in the retrospective clinical study. Time activity curves for liver were obtained by region of interest (ROI) on the whole liver. A novel hepatic functional predictor was calculated with multiple regression analysis of time activity curves. In the multiple regression function, the objective variables were the indocyanine green (ICG) retention rate at 15 min, and the explanatory variables were the liver counts in 3-min intervals until end from beginning. Then, this result was defined by IHR, and we analyzed the correlation between IHR and ICG, uptake ratio of the heart at 15 minutes to that at 3 minutes (HH15), uptake ratio of the liver to the liver plus heart at 15 minutes (LHL15), and index of convexity (IOC). RESULTS: Regression function of IHR was derived as follows: IHR=0.025*L(6)-0.052*L(12)+0.027*L(27). The multiple regression analysis indicated that liver counts at 6 min, 12 min, and 27 min were significantly related to objective variables. The correlation coefficient between IHR and ICG was 0.774, and the correlation coefficient between ICG and conventional indices (HH15, LHL15, and IOC) were 0.837, 0.773, and 0.793, respectively. IHR had good correlation with HH15, LHL15, and IOC. CONCLUSIONS: The finding results suggested that IHR would provide clinical benefit for hepatic functional assessment in the (99m)Tc-GSA scintigraphy. PMID- 26902377 TI - Magnetic Resonance Elastography: Measurement of Hepatic Stiffness Using Different Direct Inverse Problem Reconstruction Methods in Healthy Volunteers and Patients with Liver Disease. AB - The purpose of this study was to compare the mean hepatic stiffness values obtained by the application of two different direct inverse problem reconstruction methods to magnetic resonance elastography (MRE). Thirteen healthy men (23.2+/-2.1 years) and 16 patients with liver diseases (78.9+/-4.3 years; 12 men and 4 women) were examined for this study using a 3.0 T-MRI. The healthy volunteers underwent three consecutive scans, two 70-Hz waveform and a 50-Hz waveform scans. On the other hand, the patients with liver disease underwent scanning using the 70-Hz waveform only. The MRE data for each subject was processed twice for calculation of the mean hepatic stiffness (Pa), once using the multiscale direct inversion (MSDI) and once using the multimodel direct inversion (MMDI). There were no significant differences in the mean stiffness values among the scans obtained with two 70-Hz and different waveforms. However, the mean stiffness values obtained with the MSDI technique (with mask: 2895.3+/ 255.8 Pa, without mask: 2940.6+/-265.4 Pa) were larger than those obtained with the MMDI technique (with mask: 2614.0+/-242.1 Pa, without mask: 2699.2+/-273.5 Pa). The reproducibility of measurements obtained using the two techniques was high for both the healthy volunteers [intraclass correlation coefficients (ICCs): 0.840-0.953] and the patients (ICC: 0.830-0.995). These results suggest that knowledge of the characteristics of different direct inversion algorithms is important for longitudinal liver stiffness assessments such as the comparison of different scanners and evaluation of the response to fibrosis therapy. PMID- 26902378 TI - A Novel Evaluation Method for Displacement between Carbon Beam Axis and Positioning X-ray Axis Using an Imaging Plate. AB - PURPOSE: We developed an evaluation method for easily calculating displacement directly between the carbon beam axis and positioning X-ray axis. METHODS: A verification image was acquired by irradiating an imaging plate with a carbon beam and X-ray. The X-ray passed through a lead plate inserted in the range compensator holder. The displacement was calculated on the verification image from the center of a wire irradiated with carbon using a multi leaf collimator (MLC) and a wire irradiated with X-ray also using MLC. The accuracy of the method was evaluated by moving the carbon beam axis, the X-ray axis, and the setup angle. The weekly changes of vertical and lateral beams in all rooms were also evaluated. RESULTS: The displacements of the carbon beam axis and the setup angle did not influence the calculation results, whereas the displacement of the X-ray axis did (R=0.999). The displacements including weekly changes were all less than 1.00 mm. CONCLUSION: An evaluation method for calculating the displacement directly and simply between the carbon beam axis and positioning X-ray axis was developed and verified. The weekly changes of displacement between axes were evaluated to be acceptable at our facility. PMID- 26902379 TI - Image Data Mining for Pattern Classification and Visualization of Morphological Changes in Brain MR Images. AB - Hospital information systems (HISs) and picture archiving and communication systems (PACSs) are archiving large amounts of data (i.e., "big data") that are not being used. Therefore, many research projects in progress are trying to use "big data" for the development of early diagnosis, prediction of disease onset, and personalized therapies. In this study, we propose a new method for image data mining to identify regularities and abnormalities in the large image data sets. We used 70 archived magnetic resonance (MR) images that were acquired using three dimensional magnetization-prepared rapid acquisition with gradient echo (3D MP RAGE). These images were obtained from the Alzheimer's disease neuroimaging initiative (ADNI) database. For anatomical standardization of the data, we used the statistical parametric mapping (SPM) software. Using a similarity matrix based on cross-correlation coefficients (CCs) calculated from an anatomical region and a hierarchical clustering technique, we classified all the abnormal cases into five groups. The Z score map identified the difference between a standard normal brain and each of those from the Alzheimer's groups. In addition, the scatter plot obtained from two similarity matrixes visualized the regularities and abnormalities in the image data sets. Image features identified using our method could be useful for understanding of image findings associated with Alzheimer's disease. PMID- 26902380 TI - The Detectability of Iterative CT Reconstruction for Low-contrast Lesions in Hyperacute Cerebral Infarction: Assessment with Newly Developed Dedicated Head Phantoms. AB - Iterative reconstruction techniques, such as adaptive statistical iterative reconstruction (ASiR), improve the contrast-to-noise ratio of computed tomography (CT) images; however, underlying anatomical structures may nevertheless hamper detectability of low-contrast areas in clinical situations, despite using such a technique. We therefore conducted a phantom study to investigate the efficacy of ASiR in improving the detectability of low-contrast areas in the presence of brain anatomical structures. We developed dedicated head phantoms simulating hyperacute cerebral infarction and confirmed that their CT numbers were sufficiently reproducible and that observer performance in detecting low-contrast areas using these phantoms more closely resembled that in clinical situations than that using a simple phantom. The efficacy of ASiR in improving low-contrast detectability was evaluated via receiver operating characteristics analysis. The mean area under the curve (AUC) values at ASiR blend rates of 0%, 30%, 60%, and 100% were 0.57, 0.57, 0.59, and 0.59 at 200 mA; 0.83, 0.84, 0.84, and 0.90 at 500 mA; and 0.79, 0.77, 0.76, and 0.79 at 800 mA, respectively. No significant differences were noted in AUC values among ASiR blend rates at any mA setting, suggesting that ASiR does not improve the detectability of subtle low-contrast lesions seen in hyperacute cerebral infarction in clinical situations. PMID- 26902381 TI - Diagnostic and Therapeutic Assist Using 3D Images and Printers in the Respiratory Field. PMID- 26902382 TI - Activity Report 2015. PMID- 26902384 TI - Report of 5th JIRA Study Meeting for Medical Imaging Systems Industry. PMID- 26902385 TI - Instructive, Innovative, and Integrative Radiology. PMID- 26902386 TI - Introducing asymmetric functionality into MOFs via the generation of metallic Janus MOF particles. AB - Herein we report a versatile methodology for engineering metallic Janus MOF particles based on desymmetrization at interfaces, whereby each MOF particle is partially coated with a desired metal. We demonstrate that it enables the fabrication of homogeneous Janus MOF particles according to the MOF (ZIF-8, UiO 66 or UiO-66-SH), the metal (Au, Co or Pt), the MOF particle size (from the micrometer to the submicrometer regime) and the metal-film thickness (from 5 nm to 50 nm) employed. We anticipate that our strategy could be applied to impart new functionalities to MOFs, including asymmetric functionalization, magnetic guidance and motorization. PMID- 26902387 TI - Antiferromagnetic order driven chiral topological spin density waves on the repulsive Haldane-Hubbard model on square lattices. AB - In this paper, based on mean-field approach and random-phase-approximation, we study the magnetic properties of the repulsive Haldane-Hubbard model on a square lattice. We find antiferromagnetic order driven topological spin density waves beyond Landau's symmetry-breaking paradigm, for which the effective low energy physics is determined by Chern-Simons-Hopf gauge field theories with different K matrices. PMID- 26902388 TI - Zinc(II)-induced control of the internalization of a near-infrared fluorescent probe by live cells. AB - We describe zinc-promoted cellular uptake of a near-infrared fluorophore modified with a terpyridine ligand. In response to varying concentrations of exogenous zinc(II), we observed increasing cellular uptake in live HeLa cells as well as other cell lines, whereas only negligible staining was detected in the absence of zinc(II). PMID- 26902389 TI - Associations of ethnic discrimination with symptoms of anxiety and depression among Hispanic emerging adults: a moderated mediation model. AB - BACKGROUND AND OBJECTIVES: Emerging adulthood is often marked with elevated symptoms of anxiety and depression. Hispanic emerging adults may face cultural stressors such as ethnic discrimination that further increase levels of anxiety and depression symptoms. The study aims were to examine if (a) self-esteem mediated effects of ethnic discrimination on symptoms of anxiety and depression, and (b) if gender moderated the indirect effects of discrimination. DESIGN: The study design was cross-sectional self-report. METHOD: Two moderated mediation models were tested, with 1084 Hispanic emerging adults (ages 18-25) enrolled in institutions of post-secondary in the United States. RESULTS: Results indicated that (a) higher ethnic discrimination was associated with higher anxiety symptoms (beta = .05, p = .04), higher depression symptoms (beta = .06, p = .02), and lower self-esteem (beta = -.30, p < .001); (b) self-esteem mediated the associations of ethnic discrimination with anxiety and depression symptoms; and (c) gender moderated the indirect effects of discrimination, whereby self-esteem was a stronger mediator among men than women. Each moderated mediation model explained 26% of variability in symptoms of anxiety and depression, respectively. CONCLUSIONS: Findings suggest that the mediating effects of self-esteem linking ethnic discrimination with symptoms of anxiety and depression vary between genders. PMID- 26902390 TI - Sonic hedgehog stimulates neurite outgrowth in a mechanical stretch model of reactive-astrogliosis. AB - Although recovery following a stroke is limited, undamaged neurons under the right conditions can establish new connections and take on-board lost functions. Sonic hedgehog (Shh) signaling is integral for developmental axon growth, but its role after injury has not been fully examined. To investigate the effects of Shh on neuronal sprouting after injury, we used an in vitro model of glial scar, whereby cortical astrocytes were mechanically traumatized to mimic reactive astrogliosis observed after stroke. This mechanical trauma impaired neurite outgrowth from post-natal cortical neurons plated on top of reactive astrocytes. Addition of Shh to the media, however, resulted in a concentration-dependent increase in neurite outgrowth. This response was inhibited by cyclopamine and activated by oxysterol 20(S)-hydroxycholesterol, both of which modulate the activity of the Shh co-receptor Smoothened (Smo), demonstrating that Shh-mediated neurite outgrowth is Smo-dependent. In addition, neurite outgrowth was not associated with an increase in Gli-1 transcription, but could be inhibited by PP2, a selective inhibitor of Src family kinases. These results demonstrate that neurons exposed to the neurite growth inhibitory environment associated with a glial scar can be stimulated by Shh, with signaling occurring through a non canonical pathway, to overcome this suppression and stimulate neurite outgrowth. PMID- 26902391 TI - Strand breakage by decay of DNA-bound 124I provides a basis for combined PET imaging and Auger endoradiotherapy. AB - Purpose DNA ligands labelled with 125I induce cytotoxic DNA double-strand breaks (DSB), suggesting a potential for Auger endoradiotherapy. Since the 60-day half life of 125I is suboptimal for therapy, we have investigated another Auger emitter 124I, with shorter half-life (4.18 days), and the additional feature of positron-emission, enabling positron emission tomography (PET) imaging. The purpose of this study was to compare the two radionuclides on the basis of DNA DSB per decay. Materials and methods Using a 124I- (or 125I)-labelled minor groove binding DNA ligand, we investigated DNA breakage using the plasmid DNA assay. Biodistribution of the conjugate of the labelled ligand with transferrin was investigated in nude mice bearing a K562 human lymphoma xenograft. Results The probability of DSB per decay was 0.58 and 0.85 for 124I and 125I, respectively, confirming the therapeutic potential of the former. The crystal structure of the ligand DNA complex shows the iodine atom deep within the minor groove, consistent with the high efficiency of induced damage. Biodistribution studies, including PET imaging, showed distinctive results for the conjugate, compared to the free ligand and transferrin, consistent with receptor-mediated delivery of the ligand. Conclusions Conjugation of 124I-labelled DNA ligands to tumor targeting peptides provides a feasible strategy for Auger endoradiotherapy, with the advantage of monitoring tumor targeting by PET imaging. PMID- 26902392 TI - The role of partners' educational attainment in the association between HIV and education amongst women in seven sub-Saharan African countries. AB - INTRODUCTION: Individuals' educational attainment has long been considered as a risk factor for HIV. However, little attention has been paid to the association between partner educational attainment and HIV infection. METHODS: We conducted cross-sectional analysis of young women (aged 15-34) in 14 Demographic and Health Surveys from seven sub-Saharan Africa (SSA) countries with generalized HIV epidemics. We measured the degree of similarity in educational attainment (partner homophily) in 75,373 partnerships and evaluated the correlation between homophily and female HIV prevalence at the survey cluster level. We then used logistic regression to assess whether own and partner educational attainment was associated with HIV serostatus amongst 38,791 women. RESULTS: Educational attainment was positively correlated within partnerships in both urban and rural areas of every survey (Newman assortativity coefficients between 0.09 and 0.44), but this correlation was not ecologically associated with HIV prevalence. At the individual level, larger absolute differences between own and partner educational attainment were associated with significantly higher HIV prevalence amongst women. This association was heterogeneous across countries, but not between survey waves. In contrast to other women, for those aged 25-34 who had secondary or higher education, a more-educated partner was associated with lower HIV prevalence. CONCLUSIONS: HIV prevalence amongst women in SSA is associated not only with one's own education but also with that of one's partner. These findings highlight the importance of understanding how partners place individuals at risk of infection and suggest that HIV prevention efforts may benefit from considering partner characteristics. PMID- 26902393 TI - Pre-pregnancy maternal plasma cytokine levels and risks of small-for-gestational age at birth. AB - OBJECTIVES: Small-for-gestational-age (SGA) results from abnormalities of the feto-placental-maternal unit. Cytokine profiles during early pregnancy may predict placental changes that lead to SGA, however it is unknown if these altered profiles precede conception. We examined the role of maternal cytokines prior to conception as risk factors for subsequent delivery of an SGA infant. METHODS: We included a sample of 80 women and their offspring from a large trial of pre-conceptual multiple micronutrient supplementation. Plasma samples collected before conception were tested with a high sensitivity multiplex assay for IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, IFNgamma, and TNFalpha. RESULTS: Pre-conceptual IL-13 and IFNgamma were lower in women who gave birth to an SGA child than among control women (0.81 versus 1.14 pg/ml and 7.81 versus 11.01 pg/ml, respectively). Multivariable logistic regression showed that IL-13 (p = 0.029) and IFNgamma (p = 0.015) were both inversely associated with SGA. CONCLUSIONS: These results suggest maternal immune function prior to conception may indicate an unfavorable immune balance leading to placental abnormalities and high risk of SGA. Preconception assessment of cytokine profiles could potentially contribute to early detection of SGA and to the timely implementation of interventions to prevent it. PMID- 26902394 TI - Noninvasive Assessment of Early Dental Lesion Using a Dual-Contrast Photoacoustic Tomography. AB - Dental hard tissue lesions, including caries, cracked-tooth, etc., are the most prevalent diseases of people worldwide. Dental lesions and correlative diseases greatly decrease the life quality of patients throughout their lifetime. It is still hard to noninvasively detect these dental lesions in their early stages. Photoacoustic imaging is an emerging hybrid technology combining the high spatial resolution of ultrasound in deep tissue with the rich optical contrasts. In this study, a dual-contrast photoacoustic tomography is applied to detect the early dental lesions. One contrast, named B-mode, is related to the optical absorption. It is good at providing the sharp image about the morphological and macro structural features of the teeth. Another contrast, named S-mode, is associated with the micro-structural and mechanical properties of the hard tissue. It is sensitive to the change of tissue properties induced by the early dental lesions. Experiments show that the comprehensive analysis of dual-contrast information can provide reliable information of the early dental lesions. Moreover, the imaging parameter of S-mode is device-independent and it could measure tissue properties quantitatively. We expect that the proposed scheme could be beneficial for improving safety, accuracy and sensitivity of the clinical diagnosis of the dental lesion. PMID- 26902395 TI - Antibacterial activity of isolated phenolic compounds from cranberry (Vaccinium macrocarpon) against Escherichia coli. AB - Phenolic compounds from a cranberry extract were isolated in order to assess their contribution to the antibacterial activity against uropathogenic strains of Escherichia coli (UPEC). With this purpose, a total of 25 fractions from a cranberry extract were isolated using semipreparative high performance liquid chromatography (HPLC) and characterized based on the results obtained by reversed phase HPLC coupled to mass spectrometry detection. Then, the effects on UPEC surface hydrophobicity and biofilm formation of the cranberry extract as well as the purest fractions (a total of 13) were tested. As expected, the whole extract presented a powerful antibacterial activity against UPEC while the selected fractions presented a different behavior. Myricetin and quercitrin significantly decreased (p < 0.05) E. coli biofilm formation compared with the control, while dihydroferulic acid glucuronide, procyanidin A dimer, quercetin glucoside, myricetin and prodelphinidin B led to a significant decrease of the surface hydrophobicity compared with the control. The results suggest that apart from proanthocyanidins, other compounds, mainly flavonoids, can act against E. coli biofilm formation and also modify UPEC surface hydrophobicity in vitro, one of the first steps of adhesion. PMID- 26902396 TI - Sit-to-Stand and Stand-to-Sit Control Mechanisms of Two-Wheeled Wheelchair. AB - This paper presents a mechanism for standing and sitting transformation of a wheelchair using a two-wheeled inverted pendulum concept with reduced torque requirement, in simulation studies. The motivation of this work is to design a compact standing mechanism to help an elderly/disabled person with functional limitation in lower extremities to maneuver in small and confined spaces and enable them to perform standard daily life routines independently. The wheelchair system at the upright standing position is tested with different travel distances, and the challenge is to control both sit-to-stand and stand-to-sit operations in a stable manner using flexible-joint humanoid. An additional spring/damping element is incorporated at each wheel to provide a comfortable ride for the user especially during stand-to-sit transformation task. A PD-fuzzy control with modular structure is implemented, and the performance of the system is observed through visual nastran 4d (vn4d) visualization software and simulation in matlab. The stand-to-sit performance tests have shown more than 38% reduction in tilt and back seat angles fluctuation in linear travel motion using a suspension system, while the initial tilt torque needed is 50% less than the amount required in previous designs. PMID- 26902397 TI - Sexual Function after Partial Penectomy: A Prospectively Study From China. AB - The Purpose of this study was to evaluate the sexual function after partial penectomy for penile carcinoma patients. Between January 2010 and May 2013, patients treated with partial penectomy at our institution were prospectively enrolled in this study. Sexual function (IIEF-15), age, body mass index, penile length in the flaccid state after partial penectomy (PL), treatment, having a partner and psychological factors (SAS scores and SDS scores) were assessed. Univariate and multivariate linear regression analyses were performed. 43 patients were included in our study. The median age was 56 years, and the median PL was 4 cm. The preoperative IIEF-15, SAS, SDS scores were significantly different from the postoperative scores. There was no statistically significant difference between the patients treated with partial penectomy and partial penectomy+ lymphadenectomy on IIEF-15 scores. Age was negatively associated with erectile function, sexual desire, and overall satisfaction; PL was positively associated with intercourse satisfaction; SAS score was negatively associated with erectile function, orgasmic function, sexual desire, and intercourse satisfaction. Our preliminary findings suggest that the sexual function after partial penectomy was significantly reduced. The sexual function was negatively affected by age and anxiety but positively affected by PL. PMID- 26902399 TI - High glucose induces dysfunction of airway epithelial barrier through down regulation of connexin 43. AB - The airway epithelium is a barrier to the inhaled antigens and pathogens. Connexin 43 (Cx43) has been found to play critical role in maintaining the function of airway epithelial barrier and be involved in the pathogenesis of the diabetic retinal vasculature, diabetes nephropathy and diabetes skin. Hyperglycemia has been shown to be an independent risk factor for respiratory infections. We hypothesize that the down-regulation of Cx43 induced by HG alters the expression of tight junctions (zonula occludens-1 (ZO-1) and occludin) and contributes to dysfunction of airway epithelial barrier, and Cx43 plays a critical role in the process in human airway epithelial cells (16 HBE). We show that high glucose (HG) decreased the expression of ZO-1 and occludin, disassociated interaction between Cx43 and tight junctions, and then increased airway epithelial transepithelial electrical resistance (TER) and permeability by down-regulation of Cx43 in human airway epithelial cells. These observations demonstrate an important role for Cx43 in regulating HG-induced dysfunction of airway epithelial barrier. These findings may bring new insights into the molecular pathogenesis of pulmonary infection related to diabetes mellitus and lead to novel therapeutic intervention for the dysfunction of airway epithelial barrier in chronic inflammatory airway diseases. PMID- 26902398 TI - Simultaneous induction of jasmonic acid and disease-responsive genes signifies tolerance of American elm to Dutch elm disease. AB - Dutch elm disease (DED), caused by three fungal species in the genus Ophiostoma, is the most devastating disease of both native European and North American elm trees. Although many tolerant cultivars have been identified and released, the tolerance mechanisms are not well understood and true resistance has not yet been achieved. Here we show that the expression of disease-responsive genes in reactions leading to tolerance or susceptibility is significantly differentiated within the first 144 hours post-inoculation (hpi). Analysis of the levels of endogenous plant defense molecules such as jasmonic acid (JA) and salicylic acid (SA) in tolerant and susceptible American elm saplings suggested SA and methyl jasmonate as potential defense response elicitors, which was further confirmed by field observations. However, the tolerant phenotype can be best characterized by a concurrent induction of JA and disease-responsive genes at 96 hpi. Molecular investigations indicated that the expression of fungal genes (i.e. cerato ulmin) was also modulated by endogenous SA and JA and this response was unique among aggressive and non-aggressive fungal strains. The present study not only provides better understanding of tolerance mechanisms to DED, but also represents a first, verified template for examining simultaneous transcriptomic changes during American elm-fungus interactions. PMID- 26902400 TI - PHOX2A and PHOX2B are differentially regulated during retinoic acid-driven differentiation of SK-N-BE(2)C neuroblastoma cell line. AB - PHOX2B and its paralogue gene PHOX2A are two homeodomain proteins in the network regulating the development of autonomic ganglia that have been associated with the pathogenesis of neuroblastoma (NB), because of their over-expression in different NB cell lines and tumour samples. We used the SK-N-BE(2)C cell line to show that all-trans retinoic acid (ATRA), a drug that is widely used to inhibit growth and induce differentiation in NBs, regulates both PHOX2A and PHOX2B expression, albeit by means of different mechanisms: it up-regulates PHOX2A and down-regulates PHOX2B. Both mechanisms act at transcriptional level, but prolonged ATRA treatment selectively degrades the PHOX2A protein, whereas the corresponding mRNA remains up-regulated. Further, we show that PHOX2A is capable of modulating PHOX2B expression, but this mechanism is not involved in the PHOX2B down-regulation induced by retinoic acid. Our findings demonstrate that PHOX2A expression is finely controlled during retinoic acid differentiation and this, together with PHOX2B down-regulation, reinforces the idea that they may be useful biomarkers for NB staging, prognosis and treatment decision making. PMID- 26902401 TI - Curcumin is a biologically active copper chelator with antitumor activity. AB - BACKGROUND: Curcumin is a natural product with antitumor activity. The compound targets multiple cell signaling pathways, including cell survival and proliferation, caspase activation and oncogene expression. As a beta-diketone, curcumin also exists as a keto-enol tautomer that chelates transition metal ions with high affinity. PURPOSE: Copper has an integral role in promoting tumor growth and angiogenesis. This study aims to investigate whether curcumin exerts its antitumor activity through copper chelation. METHODS: Copper chelation ability of curcumin was validated by measuring US/VIS spectrum. The antitumor activity and in vivo copper removal ability of curcumin was determined in a murine xenograft model. The effect of curcumin on copper-induced MAPK activation and cell proliferation was determined in cell culture system. RESULTS: Administration of curcumin to tumor-bearing animals resulted in suppression of A549 xenograft growth, an effect that was also observed in animals treated with ammonium tetrathiomolybdate (TM), a metal chelator used for copper storage disorders clinically. The inhibition on tumor growth was associated with reduction of copper concentrations in the serum of treated groups. In cell culture studies, we showed that copper promoted cell proliferation through Erk/MAPK activation. Treatment with curcumin or U0126, a specific MAPK inhibitor, or suppression of cellular uptake of copper by siRNA knockdown of copper transporter protein 1 (CTR1) blocked copper-induced cell proliferation. CONCLUSIONS: This study therefore demonstrates curcumin antitumor effect to its copper chelation capability. These results also implicate copper chelation as a general mechanism for their action of some biologically active polyphenols like flavonoids. PMID- 26902402 TI - Vitexin reduces neutrophil migration to inflammatory focus by down-regulating pro inflammatory mediators via inhibition of p38, ERK1/2 and JNK pathway. AB - BACKGROUND: Vitexin is a flavonoid found in plants of different genus such as Vitex spp. and Crataegus spp. Despite being an important molecule present in phytomedicines and nutraceuticals, the mechanisms supporting its use as anti inflammatory remains unclear. PURPOSE: To investigate the cellular and molecular mechanisms involved in acute anti-inflammatory effect of vitexin with regard to neutrophil recruitment and macrophages activation. METHODS: Anti-inflammatory properties of vitexin were evaluated in four models of neutrophil recruitment. The regulation of inflammatory mediators release was assessed in vivo and in vitro. Vitexin (5, 15 and 30 mg/kg p.o) effects on leukocytes migration to peritoneal cavity induced by zymosan (ZY), carrageenan (CG), n-formyl-methionyl leucyl-phenylalanine (fMLP) and lipopolysaccharide (LPS) were evaluated in Swiss Webster mice and the effects on the levels of TNF-alpha, IL-1beta and IL-10 cytokines, and NO concentration were in the LPS-peritonitis. RAW 264.7 macrophages viability were determined by Alamar Blue assay as well as the capacity of vitexin in directly reducing the concentrations of TNF-alpha, IL 1beta, IL-10, NO and PGE2. Additionally, vitexin effects upon the transcriptional factors p-p38, p-ERK1/2 and p-JNK were evaluated by western blotting in cells activated with LPS. RESULTS: Vitexin was not cytotoxic (IC50 > 200 ug/ml) in RAW 264.7 and at all doses tested it effectively reduced leukocyte migration in vivo, particularly neutrophils in the peritoneal lavage, independently of the inflammatory stimulus used. It also reduced TNF-alpha, IL-1beta and NO releases in the peritoneal cavity of LPS-challenged mice. Vitexin had low cytotoxicity and was able to reduce the releases of TNF-alpha, IL-1beta, NO, PGE2 and increase in IL-10 release by LPS activated RAW 264.7 cells. Vitexin was also able to regulate transcriptional factors for pro-inflammatory mediators, reducing the expression of p-p38, p-ERK1/2 and p-JNK in LPS-elicited cells. CONCLUSIONS: Vitexin presented no in vitro cytotoxicity. Inhibition of neutrophil migration and pro inflammatory mediators release contributes to the anti-inflammatory activity of vitexin. These effects are associated with the inactivation of important signaling pathways such as p38, ERK1/2 and JNK, which act on transcription factors for eliciting induction of inflammatory response. PMID- 26902403 TI - Bone health nutraceuticals alter microarray mRNA gene expression: A randomized, parallel, open-label clinical study. AB - BACKGROUND AND OBJECTIVE: Dietary intake of fruits and vegetables has been suggested to have a role in promoting bone health. More specifically, the polyphenols they contain have been linked to physiological effects related to bone mineral density and bone metabolism. In this research, we use standard microarray analyses of peripheral whole blood from post-menopausal women treated with two fixed combinations of plant extracts standardized to polyphenol content to identify differentially expressed genes relevant to bone health. METHODS: In this 28-day open-label study, healthy post-menopausal women were randomized into three groups, each receiving one of three investigational fixed combinations of plant extracts: an anti-resorptive (AR) combination of pomegranate fruit (Punica granatum L.) and grape seed (Vitis vinifera L.) extracts; a bone formation (BF) combination of quercetin (Dimorphandra mollis Benth) and licorice (Glycyrrhiza glabra L.) extracts; and a fixed combination of all four plant extracts (AR plus BF). Standard microarray analysis was performed on peripheral whole blood samples taken before and after each treatment. Annotated genes were analyzed for their association to bone health by comparison to a gene library. RESULTS: The AR combination down-regulated a number of genes involved in reduction of bone resorption including cathepsin G (CTSG) and tachykinin receptor 1 (TACR1). The AR combination also up-regulated genes associated with formation of extracellular matrix including heparan sulfate proteoglycan 2 (HSPG2) and hyaluronoglucosaminidase 1 (HYAL1). In contrast, treatment with the BF combination resulted in up-regulation of bone morphogenetic protein 2 (BMP-2) and COL1A1 (collagen type I alpha1) genes which are linked to bone and collagen formation while down-regulating genes linked to osteoclastogenesis. Treatment with a combination of all four plant extracts had a distinctly different effect on gene expression than the results of the AR and BF combinations individually. These results could be due to multiple feedback systems balancing activities of osteoblasts and osteoclasts. CONCLUSION: In summary, this ex-vivo microarray study indicated that the pomegranate, grape seed, quercetin and licorice combinations of plant extracts modulated gene expression for both osteoclastic and osteogenic processes. PMID- 26902404 TI - Biological activities of polyphenols-enriched propolis from Argentina arid regions. AB - BACKGROUND: Propolis is a bioactive natural product collected by honeybees (Apis mellifera) from plant sources. PURPOSE: This study was undertaken to determine the effect of propolis extracts from arid region of Argentina, on the activity/expression of pro-inflammatory enzymes, and as potential free radical scavenger, antifungal and anthelmintic agent as well as to get a first insight into the polyphenolic profile of the active fractions. STUDY DESIGN/METHODS: Two propolis samples were collected in different time from hives located in Tucuman, Argentina. They are representative of the collection time of the raw material for phytotherapeutical purposes. Ethanolic extracts from both propolis were obtained. The PEEs were analyzed for total polyphenol (TP), non-flavonoid phenols (NFP) and flavonoid (FP) content followed by HPLC-DAD analysis and identification of components by HPLC-MS/MS(n). The potentiality as anti-inflammatory (LOX, COX, iNOS enzymes), antioxidant, antifungal and nematicidal was determined. RESULTS: PEEs contain high levels of TP, NFP and FP, including cinnamic acid, caffeic acid prenyl ester, caffeoyl dihydrocaffeate and caffeic acid 3,4-dihydroxyphenethyl ester, liquiritigenin, 2',4'-dihydroxychalcone and 2',4'-dihydroxy-3' methoxychalcone. The PEEs in vitro reduced the activity of LOX and COX-2. Pretreatment of RAW 264.7 cells with PEEs before the induction of inflammatory state, inhibited NO overproduction and the iNOS protein expression was significantly decreased. The PEEs exhibited antioxidant, antifungal (Candida sp.) and nematicidal effect (C. elegans). CONCLUSION: These findings show the potential use of characterized PEEs from arid regions of Argentina as phytomedicine. PMID- 26902405 TI - Apoptosis and necroptosis induced by stenodactylin in neuroblastoma cells can be completely prevented through caspase inhibition plus catalase or necrostatin-1. AB - BACKGROUND: Stenodactylin is a highly toxic plant lectin purified from the caudex of Adenia stenodactyla, with molecular structure, intracellular routing and enzyme activity similar to those of ricin, a well-known type 2 ribosome inactivating protein. However, in contrast with ricin, stenodactylin is retrogradely transported not only in peripheral nerves but also in the central nervous system. PURPOSE: Stenodactylin properties make it a potential candidate for application in neurobiology and in experimental therapies against cancer. Thus, it is necessary to better clarify the toxic activity of this compound. STUDY DESIGN: We investigated the mechanism of stenodactylin-induced cell death in the neuroblastoma-derived cell line, NB100, evaluating the implications of different death pathways and the involvement of oxidative stress. METHODS: Stenodactylin cytotoxicity was determined by evaluating protein synthesis and other viability parameters. Cell death pathways and oxidative stress were analysed through flow cytometry and microscopy. Inhibitors of apoptosis, oxidative stress and necroptosis were tested to evaluate their protective effect against stenodactylin cytotoxicity. RESULTS: Stenodactylin efficiently blocked protein synthesis and reduced the viability of neuroblastoma cells at an extremely low concentration and over a short time (1 pM, 24 h). Stenodactylin induced the strong and rapid activation of apoptosis and the production of free radicals. Here, for the first time, a complete and long lasting protection from the lethal effect induced by a toxic type 2 ribosome-inactivating protein has been obtained by combining the caspase inhibitor Z-VAD-fmk, to either the hydrogen peroxide scavenger catalase or the necroptotic inhibitor necrostatin-1. CONCLUSION: In respect to stenodactylin cytotoxicity, our results: (i) confirm the high toxicity to nervous cells, (ii) indicate that multiple cell death pathways can be induced, (iii) show that apoptosis is the main death pathway, (iv) demonstrate the involvement of necroptosis and (v) oxidative stress. PMID- 26902406 TI - Liver cancer cells are sensitive to Lanatoside C induced cell death independent of their PTEN status. AB - BACKGROUND: Hepatocellular carcinoma is the second deadliest cancer with limited treatment options. Loss of PTEN causes the P13K/Akt pathway to be hyperactive which contributes to cell survival and resistance to therapeutics in various cancers, including the liver cancer. Hence molecules targeting this pathway present good therapeutic strategies for liver cancer. HYPOTHESIS: It was previously reported that Cardiac glycosides possessed antitumor activity by inducing apoptosis of multiple cancer cells through oxidative stress. However, whether Cardiac glycoside Lanatoside C can induce oxidative stress in liver cancer cells and induce cell death both in vitro and in vivo remains unknown. METHODS: Cell viability was measured by SRB assay. Cell death analysis was investigated by propidium iodide staining with flow cytometry and PARP cleavage. DCFH-DA staining and cytometry were used for intracellular ROS measurement. Protein levels were analyzed by western blot analysis. Antitumor activity was investigated on mice xenografts in vivo. RESULTS: In this study, we found that Cardiac glycosides, particularly Lanatoside C from Digitalis ferruginea could significantly inhibit PTEN protein adequate Huh7 and PTEN deficient Mahlavu human liver cancer cell proliferation by the induction of apoptosis and G2/M arrest in the cells. Lanatoside C was further shown to induce oxidative stress and alter ERK and Akt pathways. Consequently, JNK1 activation resulted in extrinsic apoptotic pathway stimulation in both cells while JNK2 activation involved in the inhibition of cell survival only in PTEN deficient cells. Furthermore, nude mice xenografts followed by MRI showed that Lanatoside C caused a significant decrease in the tumor size. In this study apoptosis induction by Lanatoside C was characterized through ROS altered ERK and Akt pathways in both PTEN adequate epithelial and deficient mesenchymal liver cancer cells. CONCLUSION: The results indicated that Lanatoside C could be contemplated in liver cancer therapeutics, particularly in PTEN deficient tumors. This is due to Lanatoside C's stress inducing action on ERK and Akt pathways through differential activation of JNK1 and JNK2 by GSK3beta. PMID- 26902407 TI - alpha-Hederin inhibits G protein-coupled receptor kinase 2-mediated phosphorylation of beta2-adrenergic receptors. AB - BACKGROUND: Recently is has been shown that alpha- and beta-hederin increase the beta2-adrenergic responsiveness of alveolar type II cells (A549) and human airway smooth muscle cells (HASM), respectively, by inhibiting the internalization of beta2-adrenergic receptors (beta2AR) under stimulating conditions. Internalization of beta2AR is initiated by phosphorylations of certain serines and threonines by cAMP dependent protein kinase A (PKA) and G protein-coupled receptor kinases (GRK). PURPOSE: To evaluate the effect of alpha-hederin on PKA and GRK2 mediated phosphorylation of GFP-tagged beta2AR. STUDY DESIGN: To study this process we performed In-Cell Western using isoprenaline stimulated HEK293 cells overexpressing beta2AR as GFP fusion protein and specific antibodies against PKA (Ser345/346) and GRK2 (Ser355/356) phosphorylation sites. RESULTS: There was no effect found on the PKA mediated phosphorylation (n = 14) but we could show that alpha-hederin (1 uM, 12 h) significantly inhibits GRK2 mediated phosphorylation at Ser355/356 by 11 +/- 5% (n >= 29, p <= 0.01) under stimulating conditions compared to the positive control. In Forster resonance energy transfer (FRET) experiments using the isolated kinases in solution alpha-hederin did not show any influence neither to GRK2 nor to PKA. CONCLUSION: Taken together, these results indicate that alpha-hederin acts as an indirect GRK2 inhibitor leading to a reduced homologous desensitization of beta2AR-GFP in HEK293 cells. PMID- 26902408 TI - Cryptotanshinone, a compound of Salvia miltiorrhiza inhibits pre-adipocytes differentiation by regulation of adipogenesis-related genes expression via STAT3 signaling. AB - BACKGROUND: Cryptotanshinone (CT), a major tanshinone found in Salvia miltiorrhiza Bunge (Lamiaceae), has various pharmacological effects such as antitumor, anti-inflammatory, and antioxidant properties. Despite its well documented benefits in a wide range of diseases, the effect of CT on adipocyte differentiation has not been well characterized. PURPOSE: The present study was designed to determine the in vitro anti-adipogenic effect and underlying molecular mechanisms of CT using 3T3-L1 murine pre-adipocytes. METHODS: We measured the levels of intracellular triglyceride accumulation and mRNA and protein expression of key adipogenic transcription factors and their target genes. RESULTS: Treatment with CT drastically reduced lipid accumulation in a dose- and time-dependent manner. Molecular assays showed that CT effectively suppressed the expression of C/EBPbeta, C/EBPalpha, and PPARgamma and of their target adipocyte-specific genes aP2, adiponectin, and GLUT4 but activated the expression of anti-adipogenic genes such as GATA2, CHOP10, and TNF-alpha. CT treatment also inhibited the phosphorylation of STAT3 in the early phase of adipogenesis. A small-interfering-RNA-mediated knock-down of STAT3 potentiated the anti-adipogenic effect of CT. CONCLUSION: Taken together, the results suggest that CT may be a good anti-adipogenic candidate because it regulates STAT3 during early adipogenesis. PMID- 26902409 TI - Evodiamine from Evodia rutaecarpa induces apoptosis via activation of JNK and PERK in human ovarian cancer cells. AB - BACKGROUND: Evodiamine (EVO; 8,13,13b,14-tetrahydro-14-methylindolo[2'3' 3,4]pyrido[2,1-b]quinazolin-5-[7H]-one derived from the traditional herbal medicine Evodia rutaecarpa was reported to possess anticancer activity; however, the anticancer mechanism of EVO against the viability of human ovarian cancer cells is still unclear. PURPOSE: A number of studies showed that chemotherapeutic benefits may result from targeting the endoplasmic reticular (ER) stress signaling pathway. The objective of the study is to investigate the mechanism by which ER stress protein PERK plays in EVO-induced apoptosis of human ovarian cancer cells. METHODS: Cell death analysis was performed by MTT assay, DNA fragmentation assay, and Giemsa staining. DiOC6 staining was used for mitochondrial membrane potential measurement. Protein levels were analyzed by Western blotting. Pharmacological studies using MAPK inhibitors and PERK inhibitor GSK2606414 were involved. RESULTS: The viability of human ovarian cancer cells A2780, A2780CP, ES-2, and SKOV-3 was inhibited by EVO at various concentrations in accordance with increases in the percentage of apoptotic cells, DNA ladders, and cleavage of caspase 3 and poly(ADP ribose) polymerase (PARP) proteins. Decreased viability of cells was reversed by adding caspase inhibitors VAD and DEVD in SKOV-3 and A2780CP cells, and incubation of cells with JNK inhibitor SP600125 (SP) and JNKI, but not other MAPK and AKT inhibitors including PD98059, SB203580, significantly prevented the apoptosis elicited by EVO in human ovarian cancer cells. Furthermore, increased expression of phospho-eIF2alpha (peIF2alpha) and phospho-PERK (pPERK) proteins was detected in EVO-treated human ovarian cancer cells, and that was inhibited by adding JNK inhibitors SP600125 and JNKI. Application of a PERK inhibitor GSK2606414 showed a significant protection of human ovarian cancer cells A2780 and A2780CP from EVO-induced apoptosis. EVO disruption of mitochondrial membrane potential (MMP) was also inhibited by adding JNK or PERK inhibitors. The structure-activity relationship study indicated that the alkyl group at position 14 in EVO is important for apoptosis induction via activation of JNK and PERK in human ovarian cancer cells. CONCLUSION: Evidence supporting EVO induction of apoptosis via activation of JNK and PERK to disrupt MMP in human ovarian cancer cells is provided, and the alkyl at position 14 is a critical substitution for the apoptotic actions of EVO. PMID- 26902411 TI - Hildebert Wagner Award Laureate announcement December 2015. PMID- 26902410 TI - Tuberostemonine N, an active compound isolated from Stemona tuberosa, suppresses cigarette smoke-induced sub-acute lung inflammation in mice. AB - OBJECTIVE: Our previous study demonstrated that a Stemona tuberosa extract had significant effects on cigarette smoking (CS)-induced lung inflammation in mice. The present study evaluated the potential of tuberostemonine N (T.N) to prevent airway inflammation and suppress airway responses in a CS-induced in vivo COPD model. METHODS: T.N was isolated from the root of ST and analyzed using 1D and 2D NMR. The purity of T.N was accessed using HPLC-ELSD analysis. C57BL/6 mice in this study were whole-body exposed to mainstream CS or room air for 4 weeks, and T.N (1, 5 and 10 mg/kg body wt.) was administered to mice via intraperitoneal (i.p.) injection before CS exposure. The number of inflammatory cells, including neutrophils, macrophages and lymphocytes, and the amount of proinflammatory cytokines and chemokines were accessed from bronchoalveolar lavage fluid (BALF) to investigate the anti-inflammatory effects of T.N. Average alveoli size was also measured using histological analyses. RESULTS: Cellular profiles and histopathological analyses revealed that the infiltration of peribronchial and perivascular inflammatory cells decreased significantly in the T.N-treated groups compared to the CS-exposed control group. T.N significantly inhibited the secretion of proinflammatory cytokines and chemokines in BALF and decreased alveoli size in lung tissue. CONCLUSIONS: These data suggest that T.N exerts anti inflammatory effects against airway inflammation, and T.N may be a novel therapeutic agent for lung diseases, such as COPD. PMID- 26902412 TI - A rare cationic building block that generates a new type of polyhedral network with "cross-linked" pto topology. AB - A rare 8-connected cationic building block, [Cu2L8(MU-MF6)](2+) (L = pyridyl ligand, M = Si, Ti, Ge, Zr or Sn), enables the formation of a small cubicuboctahedral supramolecular building block, SBB, when complexed by 2,4,6 tris(4-pyridyl)pyridine. The coordination network resulting from fusing the square faces of the SBBs can be described as a pto topology in which half of the square faces are cross-linked by MF6(2-) moieties, and represents the first example of a new 3,5-c topology. PMID- 26902413 TI - Kinetic mechanism of Plasmodium falciparum hypoxanthine-guanine-xanthine phosphoribosyltransferase. AB - Plasmodium falciparum hypoxanthine-guanine-xanthine phosphoribosyltransferase (PfHGXPRT) exhibits a kinetic mechanism that differs from that of the human homolog. Human HGPRT follows a steady-state ordered mechanism, wherein PRPP binding precedes the binding of hypoxanthine/guanine and release of product IMP/GMP is the rate limiting step. In the current study, initial velocity kinetics with PfHGXPRT indicates a steady-state ordered mechanism, wherein xanthine binding is conditional to the binding of PRPP. The value of the rate constant for IMP dissociation is greater by 183-fold than the kcat for hypoxanthine phosphoribosylation and this results in the absence of burst in progress curves from pre-steady-state kinetics. Further, IMP binding is 1000 times faster (4s(-1) at 0.5MUM IMP) when compared to the kcat (3.9+/-0.2*10(-3)s( 1)) for the reverse IMP pyrophosphorolysis reaction. These results lend support to the fact that in both forward and reverse reactions, the process of chemical conversion (formation of IMP/hypoxanthine) is slow and the events of ligand association and dissociation are faster. PMID- 26902415 TI - Let's Not SPRINT to Judgment About New Blood Pressure Goals. PMID- 26902414 TI - Tryptophan 299 is a conserved residue of human pregnane X receptor critical for the functional consequence of ligand binding. AB - PXR is a xenobiotic receptor that regulates drug metabolism by regulating the expression of drug-metabolizing enzymes including CYP3A4. It can be modulated by chemicals with different structures, functional groups and sizes. X-ray crystal structures of the ligand binding domain of human PXR (hPXR) alone or bound with agonists reveal a highly hydrophobic ligand binding pocket where the aromatic amino acid residue W299 appears to play a critical role in ligand binding. Here, we have investigated the role of W299 on the functional consequence of hPXR ligand binding. We first found that substitution of W299 with a hydrophobic residue retained its response to rifampicin, but substitution with a charged residue altered such agonist response in activating the transcription of CYP3A4. The activity of hPXR mutants on CYP3A4 expression correlates with the ability of hPXR mutants to interact with co-activator SRC-1. We further demonstrated that the effect of replacing W299 by residues with different side chains on hPXR's function varied depending on the specific agonist used. Finally we interpreted the cellular activity of the hPXR mutants by analyzing reported crystallographic data and proposing a model. Our findings reveal the essential role of W299 in the transactivation of hPXR in response to agonist binding, and provide useful information for designing modulators of hPXR. PMID- 26902417 TI - An unknown male increases sexual incentive motivation and partner preference: Further evidence for the Coolidge effect in female rats. AB - The Coolidge effect is the resumption of copulatory behavior induced by a novel sexual partner that has been reported in several species. The term is also used in males when they resume mating when exposed to an unknown receptive female after they have reached sexual exhaustion. Only few studies have evaluated the Coolidge effect in females. In the present study we further evaluated this possibility using the sexual incentive motivation (SIM) and the partner preference (PP) tests. Ovariectomized rats were hormonally primed and allowed to mate for 1h controlling the sexual interaction (paced mating) or in a condition where they were unable to pace the sexual encounters. In the SIM and PP tests, females were exposed to the male with whom they had mated before (known male) or with an unknown, sexually experienced one (unknown male). Regardless whether they paced the sexual interaction, all females showed clear preference for the unknown male but females that paced the sexual contacts spent more time in the incentive zone of the unknown male than females that could not pace the sexual interaction. Similar results were observed in the PP test. Both groups of females spent more time in the compartment of the previously unknown male than in that of the known one, but received the same amount of sexual stimulation, i.e., mounts, intromissions and ejaculations from both males. No preference was found when the females were tested in the SIM test between an unknown male and a sexually receptive female. The results further support the existence of a Coolidge effect in female rats that is more apparent if they pace the sexual interaction. PMID- 26902416 TI - The miR-34a-LDHA axis regulates glucose metabolism and tumor growth in breast cancer. AB - Lactate dehydrogenase A (LDHA) is involved in a variety of cancers. The purpose of this study was to investigate the expression, prognostic roles and function of LDHA in breast cancer. We found that LDHA was upregulated in both breast cancer cell lines and clinical specimens using quantitative real-time PCR (qRT-PCR). Immunohistochemistry (IHC) analysis of tissue microarrays (TMAs) showed that high LDHA expression was associated with cell proliferation, metastasis and poor patient overall survival (OS) and disease free survival (DFS). Furthermore, we found that LDHA promoted glycolysis and cell proliferation in vitro and in vivo. We also performed luciferase reporter assays and found that LDHA was a direct target of miR-34a. Repression of LDHA by miR-34a suppressed glycolysis and cell proliferation in breast cancer cells in vitro. Our findings provide clues regarding the role of miR-34a as a tumor suppressor in breast cancer through the inhibition of LDHA both in vitro and in vivo. Targeting LDHA through miR-34a could be a potential therapeutic strategy in breast cancer. PMID- 26902419 TI - Changes in Academic Demands and Attention-Deficit/Hyperactivity Disorder in Young Children. PMID- 26902418 TI - Disentangling the determinants of species richness of vascular plants and mammals from national to regional scales. AB - Understanding the spatial patterns in species richness gets new implication for biodiversity conservation in the context of climate change and intensified human intervention. Here, we created a database of the geographical distribution of 30,519 vascular plant species and 565 mammal species from 2,376 counties across China and disentangled the determinants that explain species richness patterns both at national and regional scales using spatial linear models. We found that the determinants of species richness patterns varied among regions: elevational range was the most powerful predictor for the species richness of plants and mammals across China. However, species richness patterns in the Qinghai-Tibetan Plateau Region (QTR) are quite unique, where net primary productivity was the most important predictor. We also detected that elevational range was positively related to plant species richness when it is less than 1,900 m, whereas the relationship was not significant when elevational range is larger than 1,900 m. It indicated that elevational range often emerges as the predominant controlling factor within the regions where energy is sufficient. The effects of land use on mammal species richness should attract special attention. Our study suggests that region-specific conservation policies should be developed based on the regional features of species richness. PMID- 26902420 TI - Distinct mechanisms for opposite functions of homeoproteins Cdx2 and HoxB7 in double-strand break DNA repair in colon cancer cells. AB - Homeobox genes, involved in embryonic development and tissues homeostasis in adults, are often deregulated in cancer, but their relevance in pathology is far from being fully elucidated. In colon cancers, we report that the homeoproteins HoxB7 and Cdx2 exhibit different heterogeneous patterns, Cdx2 being localized in moderately altered neoplasic glands in contrast to HoxB7 which predominates in poorly-differentiated areas; they are coexpressed in few cancer cells. In human colon cancer cells, both homeoproteins interact with the DNA repair factor KU70/80, but functional studies reveal opposite effects: HoxB7 stimulates DNA repair and cell survival upon etoposide treatment, whereas Cdx2 inhibits both processes. The stimulatory effect of HoxB7 on DNA repair requires the transactivation domain linked to the homeodomain involved in the interaction with KU70/80, whereas the transactivation domain of Cdx2 is dispensable for its inhibitory function, which instead needs the homeodomain to interact with KU70/80 and the C-terminal domain. Thus, HoxB7 and Cdx2 respectively use transcription dependent and -independent mechanisms to stimulate and inhibit DNA repair. In addition, in cells co-expressing both homeoproteins, Cdx2 lessens DNA repair activity through a novel mechanism of inhibition of the transcriptional function of HoxB7, whereby Cdx2 forms a molecular complex with HoxB7 and prevents it to recognize its target in the chromatin. These results point out the complex interplay between the DSB DNA repair activity and the homeoproteins HoxB7 and Cdx2 in colon cancer cells, making the balance between these factors a determinant and a potential indicator of the efficacy of genotoxic drugs. PMID- 26902421 TI - Akt phosphorylates myc-associated zinc finger protein (MAZ), releases P-MAZ from the p53 promoter, and activates p53 transcription. AB - The p53 protein is a cell cycle regulator. When the cell cycle progresses, p53 plays an important role in putting a brake on the G1 phase to prevent unwanted errors during cell division. Akt is a downstream kinase of receptor tyrosine kinase. Upon activation, Akt phorphorylates IKK that then phosphorylates IkappaB and releases NF-kappaB, leading to transcriptional activation of Dmp1. Dmp1 is a transcriptional activator of Arf. It has been known that oncogene activation stabilizes p53 through transcriptional activation of Arf, which then binds and inhibits Mdm2. In the current study, we show that myc-associated zinc finger protein (MAZ) is a transcriptional repressor of the p53 promoter. Akt phosphorylates MAZ at Thr385, and the phosphorylated MAZ is released from the p53 promoter, leading to transcriptional activation of p53, a new mechanism that contributes to increased p53 protein pool during oncogene activation. PMID- 26902422 TI - Let-7a suppresses macrophage infiltrations and malignant phenotype of Ewing sarcoma via STAT3/NF-kappaB positive regulatory circuit. AB - The interaction between tumors cells, tumor-derived humoral factors and the bone marrow in the bone niches has been shown to be essential for bone tumor initiation and promotion. Among the tumor stromal cells, tumor-associated macrophages (TAMs) are usually the most abundant immune population. Previously, we reported that let-7a functions as a tumor suppressor in ES. Herein, we found that the suppressive effects are not only limited on the malignant phenotype of tumor cells but also on the regulation of macrophage infiltration. We observed that the let-7a expression is negatively related to macrophage infiltrations in ES. Moreover, overexpression of putative ts-miRNA let-7a significantly suppressed the recruitment of PBMCs in vitro and decreased the macrophage infiltrations in ES-xenografted tumors in vivo. Most importantly, a positive regulatory feedback loop consisting of let-7a, signal transducer and activator of transcription 3 (STAT3), and nuclear factor-kappa B (NF-kappaB) (let-7a/STAT3/NF-kappaB) was involved in let-7a-mediated suppressive effects. These data might provide evidence of a novel intracellular signaling network function in ES pathogenesis, and manipulating this novel feedback loop will have therapeutic potential for ES patients. PMID- 26902423 TI - AZGP1 suppresses epithelial-to-mesenchymal transition and hepatic carcinogenesis by blocking TGFbeta1-ERK2 pathways. AB - Zinc-alpha2-glycoprotein 1 (AZGP1) has been found to play important roles in TGF beta1 induced epithelial-to-mesenchymal transition (EMT). However, the mechanisms of AZGP1 inhibiting EMT and its therapeutic potential remain unknown in hepatocellular carcinoma (HCC). AZGP1, TGF-beta1 or ERK2 expressions were examined in liver tissues of HCC patients and rat model. The effect of AZGP1 on EMT and crosstalking of TGFbeta1-ERK2 signaling in human hepatic cancer cell was tested in vitro and in vivo. Hepatic expression of AZGP1 was nearly deficient in HCC patients and rats. It was proved that AZGP1 has the ability of down regulating mesenchymal markers, up-regulating epithelial marker, inhibiting cell invasion and suppressing EMT in human HCC cells. The results clarified that AZGP1 has the effect on blocking TGF-beta1 mediated ERK2 phosphorylation leading to depressing EMT and invasive potential in vitro. Local injection of AZGP1 mimic in vivo could significantly withhold lung metastasis in HCC. In conclusion, loss of AZGP1 could trigger EMT induced by TGFbeta1-ERK2 signaling, confuse in energy metabolism, reduce cell proliferation and apoptosis, activate survival signals and promote invasion. Up-regulation of AZGP1 should be proposed to reverse EMT and might be a new promising therapy for HCC. PMID- 26902424 TI - Tumor heterogeneity and circulating tumor cells. AB - In patients with cancer, individualized treatment strategies are generally guided by an analysis of molecular biomarkers. However, genetic instability allows tumor cells to lose monoclonality and acquire genetic heterogeneity, an important characteristic of tumors, during disease progression. Researchers have found that there is tumor heterogeneity between the primary tumor and metastatic lesions, between different metastatic lesions, and even within a single tumor (either primary or metastatic). Tumor heterogeneity is associated with heterogeneous protein functions, which lowers diagnostic precision and consequently becomes an obstacle to determining the appropriate therapeutic strategies for individual cancer patients. With the development of novel testing technologies, an increasing number of studies have attempted to explore tumor heterogeneity by examining circulating tumor cells (CTCs), with the expectation that CTCs may comprehensively represent the full spectrum of mutations and/or protein expression alterations present in the cancer. In addition, this strategy represents a minimally invasive approach compared to traditional tissue biopsies that can be used to dynamically monitor tumor evolution. The present article reviews the potential efficacy of using CTCs to identify both spatial and temporal tumor heterogeneity. This review also highlights current issues in this field and provides an outlook toward future applications of CTCs. PMID- 26902425 TI - High TDP43 expression is required for TRIM16-induced inhibition of cancer cell growth and correlated with good prognosis of neuroblastoma and breast cancer patients. AB - Tripartite Motif-containing protein 16 (TRIM16) is a member of a large family of tripartite motif (TRIM) proteins, that has been implicated in the pathogenesis of multiple cancers. However, the mechanism by which TRIM16 acts as a tumour suppressor is currently unknown. We used the versatile yeast two-hybrid assay on a cDNA library from human testes, which has relative high TRIM16 expression, to identify potential TRIM16-binding proteins. We identified transactive response DNA-binding protein 43 (TDP43) as a novel TRIM16 binding protein. Co immunoprecipitation assay demonstrated that TDP43 bound TRIM16 in neuroblastoma and breast cancer cells. Enforced over-expression of TRIM16 increased the protein half-life of TDP43, through the inhibition of the proteosomal degradation pathway. High levels of TRIM16 and TDP43 are associated with good prognosis in both human neuroblastoma and breast cancer tissues. Importantly, we found TDP43 expression was required for TRIM16-induced inhibition of neuroblastoma and breast cancer cell growth and the repressive effect of TRIM16 on cell cycle regulatory proteins, E2F1 and pRb. Taken together, our data suggest that TRIM16 and TDP43 are both good prognosis indicators; also we showed that TRIM16 inhibits cancer cell viability by a novel mechanism involving interaction and stabilisation of TDP43 with consequent effects on E2F1 and pRb proteins. PMID- 26902427 TI - Living with pain in ankylosing spondylitis: a qualitative study. AB - BACKGROUND: Despite various quantitative studies reporting that pain is among the most serious problem in ankylosing spondylitis (AS), no detailed qualitative studies address how pain affects the life of patients with AS. AIM: To explore AS patients' experiences with pain and its effect on their lives. DESIGN: Descriptive qualitative study. METHODS: Data were collected by individual in depth interviews. Colaizzi's phenomenological data analysis was performed. RESULTS: During periods of pain, participants indicated that they experienced difficulty with performing their daily routine activities and meeting their personal needs. Pain also prevented them from fulfilling their responsibilities in their families, inhibited their social relations, and posed problems at their workplace. Due to the negative effects of pain in their lives, the participants felt helplessness, fear, stress, sadness, and unhappiness. CONCLUSIONS: Added to being asked about the quantity of pain, patients with AS should be questioned about how pain affects their lives. PMID- 26902426 TI - Principles for Predicting RNA Secondary Structure Design Difficulty. AB - Designing RNAs that form specific secondary structures is enabling better understanding and control of living systems through RNA-guided silencing, genome editing and protein organization. Little is known, however, about which RNA secondary structures might be tractable for downstream sequence design, increasing the time and expense of design efforts due to inefficient secondary structure choices. Here, we present insights into specific structural features that increase the difficulty of finding sequences that fold into a target RNA secondary structure, summarizing the design efforts of tens of thousands of human participants and three automated algorithms (RNAInverse, INFO-RNA and RNA-SSD) in the Eterna massive open laboratory. Subsequent tests through three independent RNA design algorithms (NUPACK, DSS-Opt and MODENA) confirmed the hypothesized importance of several features in determining design difficulty, including sequence length, mean stem length, symmetry and specific difficult-to-design motifs such as zigzags. Based on these results, we have compiled an Eterna100 benchmark of 100 secondary structure design challenges that span a large range in design difficulty to help test future efforts. Our in silico results suggest new routes for improving computational RNA design methods and for extending these insights to assess "designability" of single RNA structures, as well as of switches for in vitro and in vivo applications. PMID- 26902428 TI - Endometriosis-Derived Stromal Cells Secrete Thrombin and Thromboxane A2, Inducing Platelet Activation. AB - Platelets have been recently revealed to play important roles in the development of endometriosis. However, it is unclear whether endometriotic lesions can secrete any platelet inducers outside the menstruation window. Hence, this study was undertaken to see whether endometriosis-derived stromal cells secrete platelet activators and cause platelet activation. We employed in vitro experimentation using primary ectopic endometrial stromal cells (EESCs) and platelets from healthy male volunteers and evaluated the extent of platelet aggregation by aggregometer and the platelet activation rate by flow cytometry using supernatants harvested from EESCs of different cell densities. We also measured the concentration of thromboxane B2 (TXB2), a metabolite of thromboxane A2 (TXA2), and thrombin activity in supernatants harvested from EESCs of different densities and evaluated the extent of platelet aggregation after treatment of EESCs with hirudin, Ozagrel, and apyrase. Finally, the concentration of TXB2, thrombin, and transforming growth factor beta1 (TGF-beta1) in platelets cocultured with different densities of EESCs is measured by enzyme-linked immunosorbent assay. We found that EESCs secrete thrombin and TXA2 and induce platelet activation and aggregation in a density-dependent fashion. Treatment of platelets with EESCs resulted in increased concentration of TXB2, thrombin, and TGF-beta1 in a density-dependent manner. Treatment of EESCs with hirudin and Ozagrel, but not apyrase, resulted in significant suppression of platelet aggregation. Thus, given recently reported effects of activated platelets on the cell behaviors of EESCs and endometriotic lesions in general, our findings establish that endometriotic lesions and platelets engage active cross-talks in the development of endometriosis, highlighting the importance of lesion microenvironment in endometriosis. PMID- 26902429 TI - Phenotypic and Functional Characterization of Mesenchymal Stem/Multipotent Stromal Cells From Decidua Parietalis of Human Term Placenta. AB - Mesenchymal stem/multipotent stromal cells (MSCs) from the human placenta show stem cell-like properties useful for regenerative medicine. Previously, we reported that MSCs isolated from the fetal part of human term placentae have characteristics, which make them a potential candidate for regenerative medicine. In this study, we characterized MSC isolated from the maternal part of human term placenta. The MSCs were isolated from the decidua parietalis (DPMSCs) of human placenta using a digestion method and characterized by colony-forming unit assay and the expression of MSC markers by flow cytometry technique. In addition, DPMSC differentiation into the 3 mesenchymal lineages was also performed. Moreover, the gene and protein expression profiles of DPMSCs were identified by real-time polymerase chain reaction and flow cytometry techniques, respectively. Furthermore, proteins secreted by DPMSCs were detected by sandwich enzyme-linked immunosorbent assays. Finally, the proliferation and migration potentials of DPMSCs were also determined. The DPMSCs were positive for MSC markers and negative for hematopoietic and endothelial markers, as well as costimulatory molecules and HLA-DR. Functionally, DPMSCs formed colonies and differentiated into chondrocytes, osteocytes, and adipocytes. In addition, they proliferated and migrated in response to different stimuli. Finally, they expressed and secreted many biological and immunological factors with multiple functions. Here, we carry out an extensive characterization of DPMSCs of human placenta. We report that these cells express and secrete a wide range of molecules with multiple functions, and therefore, we suggest that these cells could be an attractive candidate for cell-based therapy. PMID- 26902430 TI - In Estimated Good Prognosis Patients Could Unexpected "Hyporesponse" to Controlled Ovarian Stimulation be Related to Genetic Polymorphisms of FSH Receptor? AB - It has been reported that 10% to 15% of young normogonadotrophic women show suboptimal response to standard gonadotropin-releasing hormone-a long protocol. These patients require higher doses of exogenous follicle-stimulating hormone (FSH). This phenomenon could be associated with genetic characteristics. In this study, FSH receptor polymorphism was retrospectively evaluated in 42 normoresponder young women undergoing an in vitro fertilization/intracytoplasmic sperm injection cycle; patients were stratified according to recombinant human FSH (r-hFSH) consumption. We selected 17 normoresponder young patients who required a cumulative dose of recombinant FSH (rFSH) >2500 UI (group A). A control group was randomly selected among patients who required a cumulative dose of rFSH <2500 UI (group B). Follicle-stimulating hormone receptor (FSH-R) 307Ala and 680Ser variants were analyzed in all our patients. Our results show that the mean number of rFSH vials (36.3 +/- 7.5 vs 28.6 +/- 4.5, P = .0001) and days of stimulation (12.7 +/- 2.4 vs 10.8 +/- 2.8, P = .03) were significantly lower in group B, whereas the number of oocytes retrieved (7.1 +/- 1.5 vs 9.6 +/- 2.4; P = .0005) and the average number of embryos transferred (2.1 +/- 0.7 vs 2.7 +/- 0.4; P = .001) were significantly lower in group A. Estradiol serum levels on the human chorionic gonadotrophin day were significantly lower in group A (997.8 +/- 384.9 pg/mL vs 1749.1 +/- 644.4; P = .0001). The incidence of the Ser/Ser genotype was higher in patients with higher r-hFSH consumption (group A; P = .02). Based on our results, we hypothesize an association between the FSH-R polymorphisms and a "hyporesponse" to exogenous FSH. PMID- 26902432 TI - Electrospun pH-sensitive core-shell polymer nanocomposites fabricated using a tri axial process. AB - A modified tri-axial electrospinning process was developed for the generation of a new type of pH-sensitive polymer/lipid nanocomposite. The systems produced are able to promote both dissolution and permeation of a model poorly water-soluble drug. First, we show that it is possible to run a tri-axial process with only one of the three fluids being electrospinnable. Using an electrospinnable middle fluid of Eudragit S100 (ES100) with pure ethanol as the outer solvent and an unspinnable lecithin-diclofenac sodium (PL-DS) core solution, nanofibers with linear morphology and clear core/shell structures can be fabricated continuously and smoothly. X-ray diffraction proved that these nanofibers are structural nanocomposites with the drug present in an amorphous state. In vitro dissolution tests demonstrated that the formulations could preclude release in acidic conditions, and that the drug was released from the fibers in two successive steps at neutral pH. The first step is the dissolution of the shell ES100 and the conversion of the core PL-DS into sub-micron sized particles. This frees some DS into solution, and later the remaining DS is gradually released from the PL-DS particles through diffusion. Ex vivo permeation results showed that the composite nanofibers give a more than twofold uplift in the amount of DS passing through the colonic membrane as compared to pure DS; 74% of the transmitted drug was in the form of PL-DS particles. The new tri-axial electrospinning process developed in this work provides a platform to fabricate structural nanomaterials, and the core-shell polymer-PL nanocomposites we have produced have significant potential applications for oral colon-targeted drug delivery. STATEMENT OF SIGNIFICANCE: A modified tri-axial electrospinning is demonstrated to create a new type of core shell pH-sensitive polymer/lipid nanocomposites, in which an electrospinnable middle fluid is exploited to support the un-spinnable outer and inner fluids. The structural nanocomposites are able to provide a colon-targeted sustained release and an enhanced permeation performance of diclofenac sodium. The developed tri axial process can provide a platform for fabricating new structural nanomaterials with high quality. The strategy of a combined usage of polymeric excipients and phospholipid in a core-shell format should provide new possibilities of developing novel drug delivery systems for efficacious oral administration of poorly-water soluble drugs. PMID- 26902434 TI - NHS overspend reaches L2.3bn. PMID- 26902433 TI - Subtype analysis of Blastocystis sp. isolates from human and canine hosts in an urban community in the Philippines. AB - Blastocystis sp. is a common gut-dwelling protist of both humans and animals. A cross-sectional survey among humans and their dogs was conducted to determine the prevalence of Blastocystis infection and to characterize the subtype (ST) distribution in an urban community in the Philippines. Fecal specimens from 1,271 humans and 145 dogs were collected and inoculated in diphasic culture medium. Prevalence of Blastocystis by culture was 13.0% (95% CI = 11.2-15.0) and 14.5% (95% CI = 9.6-21.2) for humans and dogs, respectively. A total of 168 culture isolates were genotyped using polymerase chain reaction (PCR) with seven pairs of ST-specific sequence-tagged-site (STS) primers. In humans, the ST present in this study were ST1 with 22.6% (95% CI = 17.2-29.0), ST2 with 3.1% (95% CI = 1.3-6.7), ST3 with 41.4% (95% CI= 34.9-48.6), ST4 with 14.8% (95% CI = 10.5-20.6), ST5 with 4.1% (95% CI = 2.0-8.0), and unknown ST with 13.9% (95% CI = 9.6-19.4). In dogs, the ST present in this study were ST1 with 4.3% (95% CI = 0.0-29.0), ST2 with 8.7% (95% CI = 1.3-28.0), ST3 with 17.4% (95% CI = 6.4-37.7), ST4 with 13.0% (95% CI = 3.7-33.0), ST5 with 13.0% (95% CI = 3.7-33.0), and unknown ST with 47.8% (95% CI = 29.2-67.0). This is the first study that reported Blastocystis ST4 in human and canine hosts in the Philippines. PMID- 26902435 TI - The Past and the Future. PMID- 26902431 TI - Characterization of metabolic health in mouse models of fibrillin-1 perturbation. AB - Mutations in the microfibrillar protein fibrillin-1 or the absence of its binding partner microfibril-associated glycoprotein (MAGP1) lead to increased TGFbeta signaling due to an inability to sequester latent or active forms of TGFbeta, respectively. Mouse models of excess TGFbeta signaling display increased adiposity and predisposition to type-2 diabetes. It is therefore interesting that individuals with Marfan syndrome, a disease in which fibrillin-1 mutation leads to aberrant TGFbeta signaling, typically present with extreme fat hypoplasia. The goal of this project was to characterize multiple fibrillin-1 mutant mouse strains to understand how fibrillin-1 contributes to metabolic health. The results of this study demonstrate that fibrillin-1 contributes little to lipid storage and metabolic homeostasis, which is in contrast to the obesity and metabolic changes associated with MAGP1 deficiency. MAGP1 but not fibrillin-1 mutant mice had elevated TGFbeta signaling in their adipose tissue, which is consistent with the difference in obesity phenotypes. However, fibrillin-1 mutant strains and MAGP1-deficient mice all exhibit increased bone length and reduced bone mineralization which are characteristic of Marfan syndrome. Our findings suggest that Marfan-associated adipocyte hypoplasia is likely not due to microfibril-associated changes in adipose tissue, and provide evidence that MAGP1 may function independently of fibrillin in some tissues. PMID- 26902436 TI - What Do Childbearing Women in Your Clinical Practice Look Like? AB - With cultural diversity increasing, what do the childbearing women in your practice look like? Beliefs about the central role of motherhood and the use of fertility rites in the life of a woman vary. Although individual differences exist because of the uniqueness of each woman, there are wonderfully rich cultural traditions and practices that influence what a woman believes and enacts. What constitutes a satisfying birth experience varies from woman to woman. Perinatal nurses can find many satisfying clinical experiences by being creative, flexible, and resilient in their approach to providing care. PMID- 26902438 TI - Exploratory Study of Childbearing Experiences of Women With Asperger Syndrome. AB - Increasing numbers of girls have been diagnosed with Asperger syndrome and other autism spectrum disorders (ASDs) over the past two decades; therefore, more women with ASDs are entering the childbearing phase of their lives. Little is known about the childbearing experiences of women with ASDs. This qualitative study describes the childbearing experiences of eight women with Asperger syndrome. Four major themes emerged: Processing Sensations, Needing to Have Control, Walking in the Dark, and Motherhood on My Own Terms. Clinicians can provide sensitive, individualized care by asking women with Asperger syndrome about their specific sensory experiences, counseling them about coping strategies for sensory intrusions, providing targeted support, and modifying the clinical environment to decrease distressing stimuli. PMID- 26902437 TI - A Dedicated Education Unit for Maternal-Newborn Nursing Clinical Education. AB - Designing a quality maternal-newborn clinical practice experience for undergraduate nursing students is often challenging. A dedicated education unit (DEU) is a partnership model of clinical education in which students partner with a designated unit-based nurse in providing nursing care within a typical patient care assignment. This article describes the experience of implementing a DEU in a junior level (third year) nursing practice course in a bachelor of science in nursing program curriculum. A DEU model is a perfect fit for maternal-newborn clinical learning experiences and provides a win-win outcome for academic and clinical partners as well as safe patient care. http://dx.doi.org/10.1016/j.nwh.2015.12.005. PMID- 26902439 TI - Certified Nurse-Midwives' Experiences with Gestational Weight Management. AB - Excessive gestational weight gain is associated with fetal metabolic reprogramming and subsequent childhood obesity, as well as maternal recalcitrant obesity and its successive morbidities. We conducted a review of the literature and an explorative, descriptive study of the techniques and strategies used by a subset of certified nurse-midwives to help women achieve optimal gestational weight gain. We also identified barriers to this outcome. With more effective management approaches to gestational weight gain, adverse maternal and neonatal health outcomes could potentially be prevented. http://dx.doi.org/10.1016/j.nwh.2015.12.007. PMID- 26902440 TI - Defining the Meaning of Spirituality Through a Qualitative Case Study of Sheltered Homeless Women. AB - The primary purpose of this case study was to assess the meaning of spirituality in a convenience sample of women located in an urban city in the southwest United States. The secondary purpose was to describe their lived experiences associated with spirituality. From these interviews five themes emerged: Belief in God or a Higher Power, Distinction Between Religion and Spirituality, Belief That There Is a Plan for Their Lives, Spirituality Providing Guidance for What Is Right/Wrong, and Belief That Their Lives Will Improve. These findings support the perceived fundamental importance of spirituality in the lives of homeless women. Nurses and other clinicians can use this information to develop interventions to help support women using spirituality practices and to help improve the outlook of homelessness for these women. PMID- 26902441 TI - Implementing a Protocol Using Glucose Gel to Treat Neonatal Hypoglycemia. AB - Neonatal hypoglycemia is a leading cause of admission of neonates to the NICU. Typical treatment for neonatal hypoglycemia includes supplementation with formula or, in some cases, intravenous glucose administration. These treatments, though effective at treating hypoglycemia, interrupt exclusive breastfeeding and interfere with mother-infant bonding. Our institution developed a treatment algorithm for newborns at risk for neonatal hypoglycemia. The new algorithm called for the oral administration of 40% glucose gel. This intervention resulted in a 73% decreasein admission rates to the NICU for hypoglycemia, and it supported exclusive breastfeeding, skin-to-skin contact, and mother-infant bonding. PMID- 26902442 TI - A Nurse's Guide to Supporting Physiologic Birth. AB - Physiologic birth promotes the practice of normal labor and birth, in which a woman's innate power is supported and unnecessary interventions are avoided. Nurses are in a unique position to support physiologic birth because they attend almost all births. Several resources are available to assist nurses in promoting physiologic birth, including BirthTOOLS.org, a new online resource developed by the American College of Nurse-Midwives in collaboration with other organizations. By using resources such as BirthTOOLS.org and others, nurses can become familiar with the evidence surrounding physiologic birth and can contribute to improved patient safety and quality of care by supporting physiologic birth. http://dx.doi.org/10.1016/j.nwh.2015.12.009. PMID- 26902443 TI - HIV in Pregnancy. AB - In the United States, women with HIV have the ability to make informed choices relating to their reproductive lives more now than ever before. The increasing availability of antiretroviral therapy has spurred renewed interest among many HIV-positive women in their decisions about whether to have children. It is important for perinatal nurses to understand the maternal and fetal implications of HIV in pregnancy, including parameters for treatment and the drug regimens typically used during the antepartum, intrapartum, and postpartum periods. PMID- 26902444 TI - Hypothyroidism in Women. AB - Hypothyroidism, a disease in which the thyroid gland does not make enough thyroid hormone, is the second most common endocrine disorder among women. Symptoms of hypothyroidism include fatigue, weight gain, alteration in cognition, infertility, and menstrual abnormalities. The most common cause of hypothyroidism in the United States is Hashimoto's thyroiditis. The American Thyroid Association recommends an initial screening for thyroid disease at age 35years and every 5years thereafter. Thyroid-stimulating hormone is highly sensitive to thyroid dysfunction and is used to evaluate thyroid disorders. Monotherapy with levothyroxine is the standard for treating hypothyroidism. Diagnosing hypothyroidism requires appropriate diagnostic tests to facilitate prompt diagnosis and treatment. PMID- 26902445 TI - Preventing Workplace Injuries Among Perinatal Nurses. AB - Many aspects of perinatal nursing put nurses at risk for injuries, including frequent repetitive bending, lifting of clients, and exposure to potentially large amounts of body fluids such as blood and amniotic fluid. Violence is also a potential risk with stressful family situations that may arise around childbirth. Workplace injuries put a health care facility at risk for staff turnover, decreases in the number of skilled nurses, client dissatisfaction, workers' compensation payouts, and employee lawsuits. Through the use of safety equipment, improved safety and violence training programs, "no manual lift" policies, reinforcement of personal protective equipment usage, and diligent staff training to improve awareness, these risks can be minimized. PMID- 26902446 TI - Newborn Screening. PMID- 26902447 TI - The Role of Unlicensed Assistive Personnel (Nursing Assistive Personnel) in the Care of Women and Newborns. PMID- 26902448 TI - Witnessing the Mother-Daughter Dynamic Across a Cultural Divide. PMID- 26902449 TI - Extent of Late Gadolinium Enhancement on Cardiac Magnetic Resonance Imaging in Japanese Hypertrophic Cardiomyopathy Patients. AB - BACKGROUND: In addition to the presence of late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR), the extent of LGE is considered clinically important in hypertrophic cardiomyopathy (HCM). We evaluated the extent of LGE on CMR in a large series of Japanese HCM patients. METHODS AND RESULTS: CMR was performed in 317 HCM patients (147 male). The extent of LGE was scored as the sum of LGE-positive segments in a left ventricle (LV) 17-segment model. LGE was present in 246 patients (77.6%). LGE was detected in 3.5+/-3.1 segments on average. When the patients were divided according to maximum wall thickness (mild, <20 mm; moderate, 20-29 mm; severe, >=30 mm), median LGE score increased as wall thickness increased (mild, 2 vs. moderate, 4 vs. severe, 5; P=0.000). When the patients were divided according to ejection fraction (EF) (reduced, <50%; low-normal, 50-65%; normal, >65%), median LGE score increased as EF decreased (reduced, 7 vs. low-normal, 4 vs. normal, 2; P=0.000). On multivariate analysis, reduced EF (OR, 0.947, P=0.015), pressure gradient <30 mmHg (OR, 0.359, P=0.000) and increased maximum wall thickness (OR, 1.236, P=0.000) were independent factors associated with extensive LGE. CONCLUSIONS: Progression of LGE was related to increased wall thickness, decreased contractility, and reduced intraventricular pressure gradient. PMID- 26902450 TI - Clinical Outcome of Surgical Endarterectomy for Common Femoral Artery Occlusive Disease. AB - BACKGROUND: Although common femoral artery endarterectomy (CFE) is the standard treatment for occlusive disease of the common femoral artery (CFA), several studies have noted encouraging results for endovascular therapy in this anatomical area. METHODS AND RESULTS: A retrospective multi-center study of 118 consecutive limbs from 111 symptomatic patients undergoing CFE between April 1998 and December 2014 was performed. Seventy-five CFE were performed on limbs for intermittent claudication and 43 CFE were performed for critical limb ischemia (CLI). The prevalence of perioperative complications was higher in patients with CLI than in the claudication patients. The technical success rate was 99% in all cases. The 1- and 5-year primary patency rates were 100% and 100% for claudication and 95% and 95% for CLI, respectively. The assisted-primary patency rates were 100% at both time points in both groups. Freedom from major amputation at 1 and 5 years was 100% and 100% in the claudication patients and 93% and 82% in the CLI patients, respectively. The 1- and 5-year overall survival rates were 97% and 89% in the claudication patients and 69% and 33% in the CLI patients, respectively. CONCLUSIONS: CFE is a safe, effective and durable procedure for occlusive disease of the CFA. This procedure should remain the standard treatment for this anatomical region. PMID- 26902451 TI - Optimal Use of Beta-Blockers for Congestive Heart Failure. AB - Beta-blockers are the cornerstone treatment for congestive heart failure (HF). Current HF guidelines commonly recommend beta-blockers for the treatment of HF with reduced left ventricular ejection fraction (LVEF). The effect of beta blockers, however, is less clear for HF patients with preserved LVEF, unstable severe acute HF, or right ventricular failure. This review summarizes the effect of beta-blockers in various clinical situations and suggests a strategy for optimal use. (Circ J 2016; 80: 565-571). PMID- 26902452 TI - Spirocyclic Sultam and Heterobiaryl Synthesis through Rh-Catalyzed Cross Dehydrogenative Coupling of N-Sulfonyl Ketimines and Thiophenes or Furans. AB - A useful approach is developed for the synthesis of various structurally interesting spirocyclic sultams and heterobiaryls using a cross-dehydrogenative coupling strategy that features high atom and step economy. This method employs [Cp*RhCl2]2 as a catalyst and N-sulfonylimine, a weak coordinating group, as an efficient directing group to assist C-H activation. A number of the coupled products were converted into interesting molecules through further synthetic transformations. PMID- 26902453 TI - Chlorine-Induced In Situ Regulation to Synthesize Graphene Frameworks with Large Specific Area for Excellent Supercapacitor Performance. AB - Three-dimensional (3D) graphene frameworks are usually limited by a complicated preparation process and a low specific surface area. This paper presents a facile suitable approach to effectively synthesize 3D graphene frameworks (GFs) with large specific surface area (up to 1018 m(2) g(-1)) through quick thermal decomposition from sodium chloroacetate, which are considerably larger than those of sodium acetate reported in our recent study. The chlorine element in sodium chloroacetate may possess a strong capability to induce in situ activation and regulate graphene formation during pyrolysis in one step. These GFs can be applied as excellent electrode materials for supercapacitors and can achieve an enhanced supercapacitor performance with a specific capacitance of 266 F g(-1) at a current density of 0.5 A g(-1). PMID- 26902454 TI - Stimulated Raman adiabatic passage in a three-level superconducting circuit. AB - The adiabatic manipulation of quantum states is a powerful technique that opened up new directions in quantum engineering--enabling tests of fundamental concepts such as geometrical phases and topological transitions, and holding the promise of alternative models of quantum computation. Here we benchmark the stimulated Raman adiabatic passage for circuit quantum electrodynamics by employing the first three levels of a transmon qubit. In this ladder configuration, we demonstrate a population transfer efficiency >80% between the ground state and the second excited state using two adiabatic Gaussian-shaped control microwave pulses. By doing quantum tomography at successive moments during the Raman pulses, we investigate the transfer of the population in time domain. Furthermore, we show that this protocol can be reversed by applying a third adiabatic pulse, we study a hybrid nondiabatic-adiabatic sequence, and we present experimental results for a quasi-degenerate intermediate level. PMID- 26902455 TI - Diversity between mammalian tolloid proteinases: Oligomerisation and non catalytic domains influence activity and specificity. AB - The mammalian tolloid family of metalloproteinases is essential for tissue patterning and extracellular matrix assembly. The four members of the family: bone morphogenetic protein-1 (BMP-1), mammalian tolloid (mTLD), tolloid-like (TLL)-1 and TLL-2 differ in their substrate specificity and activity levels, despite sharing similar domain organization. We have previously described a model of substrate exclusion by dimerisation to explain differences in the activities of monomeric BMP-1 and dimers of mTLD and TLL-1. Here we show that TLL-2, the least active member of the tolloid family, is predominantly monomeric in solution, therefore it appears unlikely that substrate exclusion via dimerisation is a mechanism for regulating TLL-2 activity. X-ray scattering and electron microscopy structural and biophysical analyses reveal an elongated shape for the monomer and flexibility in the absence of calcium. Furthermore, we show that TLL 2 can cleave chordin in vitro, similar to other mammalian tolloids, but truncated forms of TLL-2 mimicking BMP-1 are unable to cleave chordin. However, both the N- and C-terminal non-catalytic domains from all mammalian tolloids bind chordin with high affinity. The mechanisms underlying substrate specificity and activity in the tolloid family are complex with variation between family members and depend on both multimerisation and substrate interaction. PMID- 26902456 TI - Establishment and application of a new diagnostic definition of metabolic syndrome in the Shantou region of southern China. AB - The existing definitions of metabolic syndrome (MetS) may not be fully appropriate for the Shantou population because of ethnic and regional differences. We sought to establish a 95% multivariate medical reference range (MMRR) model for diagnosing MetS in Shantou adults and to evaluate the prevalence of MetS by the MMRR, JCDCG (the Chinese Guidelines), and International Diabetes Federation (IDF) criteria. A total of 4,580 participants were recruited in Shantou, southern China. We developed a MMRR model based on the combinatorial indicatrixes method for three categorized indicatrixes. According to the developed MMRR criteria, men (women) in Shantou have MetS by meeting 3 or more of the following: waist circumference >=89 (81) cm; triglycerides level >=1.73 (1.64) mmol/L; high-density lipoprotein cholesterol level <=1.07 (1.05) mmol/L; blood pressure >=138/89 (136/85) mmHg; and fasting plasma glucose >=5.8 (5.7) mmol/L. The agreement of the MMRR with JCDCG and IDF criteria was "substantial" (both kappa > 0.68), but the recommended reference values and proportion of individual components of MetS defined by the 3 criteria differed. The population based MMRR criteria may be appropriate for diagnosing MetS in Shantou population and the model might be useful for generalization to other geographic regions. PMID- 26902458 TI - Insertion of CO2 into the carbon-boron bond of a boronic ester ligand. AB - New Ru and Zn diazafluorenyl complexes undergo C-H borylation of the diazafluorenyl ligand to form the corresponding diazafluorenylboronic ester complexes, which can insert CO2 into their C-B bonds to form boryl ester functionalities. The relevance of these new reactivities towards catalytic CO2 reduction has also been explored. PMID- 26902457 TI - Correction for Susceptibility Distortions Increases the Performance of Arterial Spin Labeling in Patients with Cerebrovascular Disease. AB - BACKGROUND AND PURPOSE: Arterial spin labeling (ASL) is an MRI technique to measure cerebral blood flow (CBF) without the need of exogenous contrast agents and is thus a promising alternative to the clinical standard dynamic susceptibility-weighted contrast-enhanced (DSC) perfusion imaging. Latest international guidelines encourage its application in the clinical setting. However, susceptibility-induced image distortions impair ASL with fast readout modules (eg Echo Planar Imaging, EPI; gradient and spin echo, GRASE). In the present study, we investigated the benefit of a distortion correction for ASL compared to DSC. METHODS: A pulsed ASL (PASL) sequence combined with a 3D-GRASE readout at multiple inflow times (multi-TI) was used and was corrected for susceptibility distortions using a FMRIB Software Library (FSL) implemented tool TOPUP. We performed qualitative (three expert raters) and quantitative (volume of interest [VOI]-based) comparisons of ASL and DSC imaging in 13 patients with chronic steno-occlusive disease. RESULTS: In the qualitative analysis, distortion correction of the images led to a strong increase in diagnostic precision of ASL compared to DSC in the anterior cerebral artery (ACA) perfusion territory, where the susceptibility artifact was most pronounced (specificity 8% vs. 75%). In the quantitative analysis, the correlation between ASL and DSC values increased for all perfusion territories with the best improvement for the ACA territory (for anterior, middle and posterior cerebral artery: ACA: rho -0.22 vs. 0.71; MCA: rho 0.58 vs. 0.76; PCA: rho 0.58 vs. 0.63). CONCLUSIONS: We showed that susceptibility distortion correction strongly improves the comparability of multi TI ASL 3D-GRASE to DSC in steno-occlusive disease. We suggest it to be implemented in ASL postprocessing routines. PMID- 26902459 TI - Caregiving services in spinal cord injury: a systematic review of the literature. AB - STUDY DESIGN: PRISMA guided systematic review. OBJECTIVES: To summarize and characterize the literature pertaining to the nature of and factors associated with caregiving services provided to individuals with spinal cord injury (SCI) and identify areas for interventional research to address the needs of care recipients. DATA SOURCES: PUBMED/Medline, CINAHL, PsycINFO, EMBASE, Social Services Abstracts and Social Work Abstracts databases. METHODS: Qualitative and quantitative peer-reviewed publications that were written in English were included if they described the nature of caregiving services in SCI, factors influencing the use of and access to caregiving services or described interventions to address caregiving needs of individuals with SCI. RESULTS: Sixteen papers were selected. The level of evidence for included studies ranged from 2 (highest) to 5 (lowest). Eleven studies described the nature of caregiving services, demographics of caregivers and recipients and factors associated with requiring care. Five studies described caregiving interventions. CONCLUSION: Caregiving services in SCI are predominantly provided by informal caregivers who are female. Quality of care from informal caregivers matches or exceeds quality of formal care. Total hours of care are dependent on the injury level and severity and care needs of the individual. Caregiver training is an important theme and has positive preliminary results on the quality of care provided. Intervention-based research is limited; further research to increase independence in activities of daily living and instrumental activities of daily living would reduce the need for caregiving hours. PMID- 26902460 TI - Abnormal cutaneous flexor reflex activity during controlled isometric plantarflexion in human spinal cord injury spasticity syndrome. AB - STUDY DESIGN: Although abnormal cutaneous reflex (CR) activity has been identified during gait after incomplete spinal cord injury (SCI), this activity has not been directly compared in subjects with and without the spasticity syndrome. OBJECTIVES: Characterisation of CR activity during controlled rest and 'ramp and hold' phases of controlled plantarflexion in subjects with and without the SCI spasticity syndrome. DESIGN: Transverse descriptive study with non parametric group analysis. SETTING: SCI rehabilitation hospital. METHODS: Tibialis Anterior (TA) reflexes were evoked by innocuous cutaneous plantar sole stimulation during rest and ramp and hold phases of plantarflexion torque in non injured subjects (n=10) and after SCI with (n=9) and without (n=10) hypertonia and/or involuntary spasm activity. Integrated TA reflex responses were analysed as total (50-300 ms) or short (50-200 ms) and long-latency (200-300 ms) activity. RESULTS: Total and long-latency TA activity was inhibited in non-injured subjects and the SCI group without the spasticity syndrome during plantarflexion torque but not in the SCI spasticity group. Furthermore, loss of TA reflex inhibition during plantarflexion correlated with time after SCI (rho=0.79, P=0.009). Moreover, TA reflex activity inversely correlated with maximum plantarflexion torque in the spasticity group (rho=-0.75, P=0.02), despite similar non-reflex TA electromyographic activity during plantarflexion after SCI in subjects with (0.11, 0.08-0.13 mV) or without the spasticity syndrome (0.09, 0.07-0.12 mV). CONCLUSIONS: This reflex testing procedure supports previously published evidence for abnormal CR activity after SCI and may characterise the progressive disinhibition of TA reflex activity during controlled plantarflexion in subjects diagnosed with the spasticity syndrome. PMID- 26902461 TI - Effect of adenovirus-mediated RNA interference of IL-1beta expression on spinal cord injury in rats. AB - STUDY DESIGN: We introduced an adenoviral vector expressing interleukin-1beta (IL 1beta) small-hairpin RNA (shRNA) into the injured spinal cords to evaluate the therapeutic potential of IL-1beta downregulation in a rat model of spinal cord injury (SCI). OBJECTIVES: The purpose of this study was to investigate the possible protective effects of the IL-1beta downregulation on traumatic SCI in rats. SETTING: Department of Orthopedic Surgery, The Second Affiliated Hospital, Fujian Medical University, Quanzhou, People's Republic of China. METHODS: An adenoviral shRNA targeting IL-1beta was constructed and injected at the T12 section 7 days before SCI. The rats' motor functions were evaluated by the Basso Beattie-Bresnahan (BBB) rating scale. Immunofluorescence, enzyme-linked immunosorbent assay, flow-cytometric analysis and western blots were also performed. RESULTS: Animals downregulating IL-1beta had significantly better recovery of locomotor function and less neuronal loss after SCI. In addition, IL 1beta downregulation significantly decreased tumor necrosis factor-alpha (TNF alpha) level and Bax expression, reduced the activity of caspase-3 and increased Bcl-2 expression after SCI. CONCLUSION: This study demonstrated that the IL-1beta downregulation may have potential therapeutic benefits for both reducing secondary damages and improving the outcomes after traumatic SCI. PMID- 26902462 TI - Impaired respiratory function and associations with health-related quality of life in people with spinal cord injury. AB - STUDY DESIGN: Follow-up measurement in a multicenter prospective cohort study. OBJECTIVES: To examine the prevalence of impaired respiratory function (pulmonary function and perceived respiratory function), the incidence of respiratory infection and the associations among these parameters in people with spinal cord injury (SCI) 5 years after initial inpatient rehabilitation. Second, we assessed associations between respiratory function and health-related quality of life (HRQOL). SETTING: Eight rehabilitation centers with specialized SCI units in the Netherlands. METHODS: Measurements were performed 5 years after discharge of inpatient rehabilitation. Pulmonary function was determined by forced vital capacity (FVC) and perceived respiratory function by self-reported cough strength and dyspnea. HRQOL was measured using the Sickness Impact Profile 68 and the 36 item Short Form Health Survey. RESULTS: One-hundred forty-seven people with SCI participated. Of this sample, 30.9% had impaired FVC, 35.9% poor or moderate cough strength, 18.4% dyspnea at rest and 29.0% dyspnea during activity. In the year before the measurements, 8.9% had had respiratory infection. FVC was associated with cough strength, but not with dyspnea. All respiratory function parameters were associated with social functioning, whereas other HRQOL domains were associated with dyspnea only. CONCLUSION: Five years after initial inpatient rehabilitation, impaired respiratory function and respiratory infection were common in people with SCI. More severely impaired respiratory function was associated with lower HRQOL. SPONSORSHIP: The Netherlands Organisation for Health Research and Development. PMID- 26902463 TI - Sociodemographic factors associated with sexual dysfunction in Mexican women with spinal cord injury. AB - OBJECTIVES: No studies have reported sexual dysfunction in Mexican women with a spinal cord injury (SCI).The objective of the present study was to determine the association between sociodemographic factors and sexual dysfunction characteristics in Mexican females with SCI. METHODS: An observational, cross sectional, descriptive study was conducted in different rehabilitation centers in Mexico City from July 2013 to November 2014. Adult females with a SCI without any gynecologic structural abnormalities, which by itself produced sexual dysfunction, were included. The Female Sexual Function Index (FSFI) was answered personally by all participants. Other variables such as AIS (American spinal injury association Impairment Scale), neurologic level, time since injury, age, relationship status, socioeconomic status, spasticity, use of antispasticity drugs, education level, antidepressant medication, Spinal Cord Independence Measure III score, offspring, work activities and neuropathic pain were considered. RESULTS: There is a high percentage of sexual dysfunction among Mexican woman with SCI (81.9%). Age range went from 18- to 78-year old (42.8+/ 15.87-year old). Time since injury went from 2 to 708 months (65.16+/-117.65 months). The study showed a negative correlation between age and the FSFI questionnaire (correlation coefficient (CC)=-0.384, P<0.001).There was no significant difference between the means (analysis of variance) of the different groups for neurologic level, socioeconomic status, spasticity and education level. CONCLUSION: Results showed that the younger the person is, the better sexual function they have, and offspring decreased sexual function and work activities increased it. Some variables showed small comparative groups (use of antidepressives/antispastics and comorbilities), which may be the reason we could not see significative differences in the means. PMID- 26902464 TI - "Does short-term variation in fetal heart rate predict fetal acidaemia?" A systematic review and meta-analysis. AB - OBJECTIVE: To evaluate the association of short-term variation (STV) of the fetal heart rate in predicting fetal acidaemia at birth. METHODS: The search strategy employed searching of electronic databases (MEDLINE, Web of Science, Scopus, and Google Scholar) and reference lists of relevant studies. Data were extracted from studies, adhering strictly to the following criteria: singleton pregnancy at >=24 weeks' gestation, computerized CTG (index test) and calculation of STV before delivery. The outcome measure was arterial pH assessed in cord blood obtained at birth. RESULTS: Meta-analysis showed moderate accuracy of STV in predicting fetal acidaemia with a sensitivity of 0.57 (95% CI: 0.45-0.68), specificity of 0.81 (95% CI: 0.69-0.89), positive likelihood ratio of 3.14 (95% CI: 2.13-4.63) and negative likelihood ratio of 0.58, (95% CI: 0.46-0.72). However, in intra-uterine growth restricted fetuses, a small improvement in detecting acidaemia was observed; with a sensitivity of 0.63 (95% CI: 0.49-0.75) and negative likelihood ratio of 0.50 (95% CI: 0.31-0.80). CONCLUSION: STV appears to be a moderate predictor for fetal acidaemia. However, its usefulness as a stand-alone test in predicting acidaemia in clinical setting remains to be determined. PMID- 26902466 TI - Comment on 'Who has a repeat abortion? Identifying women at risk of repeated terminations of pregnancy: analysis of routinely collected health care data'. PMID- 26902465 TI - Chronic Non-infectious Uveitis in Patients with Juvenile Idiopathic Arthritis. AB - PURPOSE: To describe clinical findings and analyze treatment evolution of chronic, non-infectious uveitis in patients with juvenile idiopathic arthritis (JIA). METHODS: A total of 82 patients (147 eyes) with JIA-related uveitis treated for >=2 months were included (78% females; 79% bilateral uveitis; 74% anterior uveitis). Outcome measures were visual acuity (VA), inflammation control, side-effects, and surgical procedures. RESULTS: Mean +/- SD age at diagnosis was 4.9 +/- 3.8 years; mean +/- SD follow-up time was 8.7 +/- 7.8 years. Mean VA did not significantly change throughout the study. Three (2%) eyes resulted in no light perception (NLP) vision. Thirty (37%) patients underwent 69 procedures. In total, 41 (50%) patients achieved inflammation control. TNF-alpha inhibitors were significantly associated with inflammation control. Seven (8.5%) patients stopped treatment due to side-effects. CONCLUSIONS: JIA is a cause of significant ocular morbidity. TNF-alpha inhibitor use was associated with inflammation control. Prospective, randomized, double blind clinical trials in this regard are warranted. PMID- 26902467 TI - The single and synergistic effects of the major tea components caffeine, epigallocatechin-3-gallate and L-theanine on rat sperm viability. AB - Caffeine, epigallocatechin-3-gallate (EGCG) and L-theanine are the major components of tea (Camellia sinensis L.) and the main representatives of the classes of methylxanthines, catechins and free amino acids present in this beverage. There are many studies reporting tea's health benefits, however it is not clear if those effects are mediated by a single component or a synergistic action. This study aimed to evaluate the individual and synergistic effects of tea's major components on rat epididymal spermatozoa survival and oxidative profile during 3-day storage at room temperature (RT). For that, spermatozoa were incubated with caffeine (71 MUg mL(-1)), EGCG (82 MUg mL(-1)), or L-theanine (19 MUg mL(-1)), alone or in combination. Spermatozoa viability was assessed by the eosin-nigrosin staining technique. The oxidative profile was established by evaluating the levels of carbonyl groups, protein nitration and lipid peroxidation. Supplementation of sperm storage medium with the three compounds together improved sperm viability, after 24, 48 and 72 h of incubation, relative to the control and the groups incubated with each component individually. However, at the end of the 72 h of incubation, there was an increase in protein oxidation in the group exposed to the three compounds, illustrating that the combined treatment triggers different alterations in sperm proteins during their maturational process in the epididymis. This study highlights the importance of the synergism between tea components for the beneficial effects usually attributed to this beverage, particularly in sperm storage at RT. PMID- 26902468 TI - House and Stable Fly Seasonal Abundance, Larval Development Substrates, and Natural Parasitism on Small Equine Farms in Florida. AB - House flies, Musca domestica Linnaeus, and stable flies, Stomoxys calcitrans (L.) (Diptera: Muscidae), are common pests on horse farms. The successful use of pupal parasitoids for management of these pests requires knowledge of seasonal fluctuations and biology of the flies as well as natural parasitism levels. However, these dynamics have not been investigated on small equine farms. A 1 year field study began in July 2010, in north central Florida, to determine adult fly population levels and breeding areas on four small equine farms. Weekly surveillance showed that pest flies were present year-round, though there were differences in adult population levels among farms and seasons. Fly development was not confirmed on two of the four small farms, suggesting that subtle differences in husbandry may adversely affect the development of immature flies. In six substrates previously identified as the most common among the farms, stable fly puparia were found overwhelmingly in hay mixed with equine manure and house fly puparia were found in fresh pine shavings mixed with equine manure. Natural parasitism was minimal as expected, but greatest numbers of natural parasitoids collected were of the genus Spalangia. Differences in adult and immature fly numbers recovered emphasizes the need for farm owners to confirm on site fly development prior to purchase and release of biological control agents. Additionally, due to the low natural parasitism levels and domination of parasitism by Spalangia cameroni, augmentative releases using this species may be the most effective. PMID- 26902470 TI - SNP Discovery by GBS in Olive and the Construction of a High-Density Genetic Linkage Map. AB - Genetic linkage maps are valuable tools for genetic, genomic, and crop breeding studies. Several genetic linkage maps were constructed for the olive (Olea europaea L.) genome, mainly using amplified fragment length polymorphisms (AFLPs) and simple sequence repeat (SSR) markers. However, AFLPs and SSR markers were not enough to develop a high-density olive linkage map. Genotyping-by-sequencing (GBS), a recently developed single-nucleotide polymorphism (SNP) identification methodology based on next-generation sequencing (NGS) technologies, has been demonstrated to be useful for the identification of a high number of SNP markers and the construction of high-density genetic linkage maps. In the present study, we identified a total of 10,941 SNPs from a cross between the olive cultivars 'Gemlik' and 'Edincik Su' using GBS and de novo SNP discovery implemented in the computer program "Stacks." A high-density genetic linkage map for the olive genome was constructed using 121 cross-pollinated full-sib F1 progeny and 5643 markers (21 SSRs, 203 AFLPs, and 5736 SNPs). This linkage map was composed of 25 linkage groups, covering 3049 cM of the olive genome, and the mean distance between the flanking markers was 0.53 cM. To the best of our knowledge, this map is the most saturated genetic linkage map in olive to date. We demonstrated that GBS is a valuable tool for the identification of thousands of SNPs for the construction of a saturated genetic linkage map in olive. The high-density genetic map developed in this study is a useful tool for locating quantitative trait loci and other economically important traits in the olive genome. PMID- 26902469 TI - From Violence in the Home to Physical Dating Violence Victimization: The Mediating Role of Psychological Distress in a Prospective Study of Female Adolescents. AB - Symptoms of psychological distress may be one pathway through which child maltreatment and witnessing violence in the home relate to dating violence victimization. This study examined whether psychological distress in mid adolescence mediated the link between child maltreatment and witnessing violence in early adolescence and dating violence victimization in young adulthood. The sample included female participants (N = 532) from the National Survey of Child and Adolescent Well Being who were 18 years or older in the fifth and final wave of data collection. At the time of entry into the study, participants were 12.81 (SD = 1.23) years old. Sixteen percent of participants identified as Hispanic; 53 % identified their race as White, 33 % as Black, and 11 % as American Indian. Results showed that psychological distress may play a causal role in the relationship of violence in the home to dating violence victimization. Interventions targeting psychological distress, particularly in samples at risk for child maltreatment, may reduce the risk of dating violence victimization. PMID- 26902471 TI - Genetic Relationships Among Olive (Olea europaea L.) Cultivars Native to Turkey. AB - Olive is a widely cultivated, mainly in the Mediterranean region, and economically important fruit species used as both olive oil and table olive consumption. In Turkey, more than 50 olive cultivars have been authorized for commercial plantations, representing the developmental base for the olive industry. The aim of the present study was to identify genetic relationships among the most widely grown 27 olive cultivars in Turkey, using microsatellite or simple sequence repeat markers. Nine well-known foreign olive cultivars from different countries are also included in the study to compare the Turkish cultivars. To determine genetic relationship and diversity, 10 SSR loci (DCA3, DCA9, DCA15, DCA18, UDO4, UDO9, UDO11, UDO12, UDO24, UDO28) were used. Jaccard's similarity coefficient and the UPGMA method for cluster analysis were performed using the software NTSYSpc. The results showed that the number of alleles per locus ranging from 4 (UDO4, UDO9, UDO11, UDO12, DCA15) to 12 (DCA9) presenting high polymorphism. There were no identical cultivars. High similarity was shown by cultivars Maviand Adana topagi (0.754). The most genetically divergent cultivars, Domat-Meski (0.240) and Domat-NizipYaglik (0.245), were also identified. PMID- 26902472 TI - Effect of zinc supplementation on neuronal precursor proliferation in the rat hippocampus after traumatic brain injury. AB - There is great deal of debate about the possible role of adult-born hippocampal cells in the prevention of depression and related mood disorders. We first showed that zinc supplementation prevents the development of the depression-like behavior anhedonia associated with an animal model of traumatic brain injury (TBI). This work then examined the effect of zinc supplementation on the proliferation of new cells in the hippocampus that have the potential to participate in neurogenesis. Rats were fed a zinc adequate (ZA, 30ppm) or zinc supplemented (ZS, 180ppm) diet for 4wk followed by TBI using controlled cortical impact. Stereological counts of EdU-positive cells showed that TBI doubled the density of proliferating cells 24h post-injury (p<0.05), and supplemental zinc significantly increased this by an additional 2-fold (p<0.0001). While the survival of these proliferating cells decreased at the same rate in ZA and in ZS rats after injury, the total density of newly born cells was approximately 60% higher in supplemented rats 1wk after TBI. Furthermore, chronic zinc supplementation resulted in significant increases in the density of new doublecortin-positive neurons one week post-TBI that were maintained for 4wk after injury (p<0.01). While the effect of zinc supplementation on neuronal precursor cells in the hippocampus was robust, use of targeted irradiation to eliminate these cells after zinc supplementation and TBI revealed that these cells are not the sole mechanism through which zinc acts to prevent depression associated with brain injury, and suggest that other zinc dependent mechanisms are needed for the anti-depressant effect of zinc in this model of TBI. PMID- 26902474 TI - Effect of flip-flops on lower limb kinematics during walking: a cross-sectional study using three-dimensional gait analysis. AB - BACKGROUND: Flip-flops are a popular footwear choice in warm weather however their minimalist design offers little support to the foot. AIM: To investigate the effect of flip-flops on lower limb gait kinematics in healthy adults, to measure adherence between the flip-flop and foot, and to assess the effect on toe clearance in swing. METHODS: Fifteen healthy adults (8 male, mean age 27 years) completed a three-dimensional gait analysis assessment using Codamotion. Kinematic and lower limb temporal-spatial data were captured using the Modified Helen Hayes marker set with additional markers on the hallux and flip-flop sole. RESULTS: Compared to barefoot walking, there were no differences in temporal spatial parameters walking with flip-flops. There was an increase in peak knee flexion in swing (mean difference 4.6 degrees , 95 % confidence interval (CI) [ 5.8 degrees , -3.4 degrees ], p < 0.001) and peak ankle dorsiflexion at terminal swing (mean difference 2 degrees , 95 % CI [-3 degrees , -1 degrees ], p = 0.001). Other kinematic parameters were unchanged. Peak separation between foot and flip-flop was 8.8 cm (SD 1.48), occurring at pre-swing. Minimum toe clearance of the hallux in barefoot walking measured 4.2 cm (SD 0.8). Minimum clearance of the flip-flop was 1.6 cm (SD 0.56). CONCLUSIONS: Healthy adults adapted well to flip-flops. However, separation of the flip-flop from the foot led to increased knee flexion and ankle dorsiflexion in swing, probably to ensure that the flip flop did not contact the ground and to maximise adherence to the foot. Minimum clearance of the flip-flop was low compared to barefoot clearance. This may increase the risk of tripping over uneven ground. PMID- 26902473 TI - Sex- and isoform-specific mechanism of neuroprotection by transgenic expression of P450 epoxygenase in vascular endothelium. AB - OBJECTIVE: Cytochrome P450 epoxygenases (CYP) metabolize arachidonic acid to epoxyeicosatrienoic acids (EETs), which exhibit vasodilatory, anti-inflammatory and neuroprotective actions in experimental cerebral ischemia. We evaluated the effect of endothelial-specific CYP overexpression on cerebral blood flow, inflammatory cytokine expression and tissue infarction after focal cerebral ischemia in transgenic mice. APPROACH AND RESULTS: Male and female wild-type and transgenic mice overexpressing either human CYP2J2 or CYP2C8 epoxygenases in vascular endothelium under control of the Tie2 promoter (Tie2-CYP2J2 and Tie2 CYP2C8) were subjected to 60-min middle cerebral artery occlusion (MCAO). Microvascular cortical perfusion was monitored during vascular occlusion and reperfusion using laser-Doppler flowmetry and optical imaging. Infarct size and inflammatory cytokines were measured at 24h of reperfusion by TTC and real-time quantitative PCR, respectively. Infarct size was significantly reduced in both Tie2-CYP2J2 and Tie2-CYP2C8 transgenic male mice compared to corresponding WT male mice (n=10 per group, p<0.05). Tie2-CYP2J2, but not Tie2-CYP2C8 male mice maintained higher blood flow during MCAO; however, both Tie2-CYP2J2 and Tie2 CYP2C8 had lower inflammatory cytokine expression after ischemia compared to corresponding WT males (n=10 per group for CBF and n=3 for cytokines, p<0.05). In females, a reduction in infarct was observed in the caudate-putamen, but not in the cortex or hemisphere as a whole and no differences were observed in blood flow between female transgenic and WT mice (n=10 per group). CONCLUSIONS: Overexpression of CYP epoxygenases in vascular endothelial cells protects against experimental cerebral ischemia in male mice. The mechanism of protection is in part linked to enhanced blood flow and suppression of inflammation, and is both sex- and CYP isoform-specific. PMID- 26902475 TI - Torture, healthcare and Australian immigration detention. PMID- 26902476 TI - Cutting slack and cutting corners: an ethical and pragmatic response to Arora and Jacobs' 'Female genital alteration: a compromise solution'. PMID- 26902477 TI - Female genital mutilation: multiple practices, multiple wrongs. PMID- 26902478 TI - Harm reduction and female genital alteration: a response to the commentaries. PMID- 26902479 TI - Female genital alteration: a compromise solution. AB - Despite 30 years of advocacy, the prevalence of non-therapeutic female genital alteration (FGA) in minors is stable in many countries. Educational efforts have minimally changed the prevalence of this procedure in regions where it has been widely practiced. In order to better protect female children from the serious and long-term harms of some types of non-therapeutic FGA, we must adopt a more nuanced position that acknowledges a wide spectrum of procedures that alter female genitalia. We offer a revised categorisation for non-therapeutic FGA that groups procedures by effect and not by process. Acceptance of de minimis procedures that generally do not carry long-term medical risks is culturally sensitive, does not discriminate on the basis of gender, and does not violate human rights. More morbid procedures should not be performed. However, accepting de minimis non-therapeutic f FGA procedures enhances the effort of compassionate practitioners searching for a compromise position that respects cultural differences but protects the health of their patients. PMID- 26902480 TI - Not all cultural traditions deserve respect. PMID- 26902481 TI - Applications of Rapid Evaluation of Metapopulation Persistence (REMP) in Conservation Planning for Vulnerable Fauna Species. AB - In many regions species are declining due to fragmentation and loss of habitat. If species persistence is to be achieved, ecologically informed, effective conservation action is required. Yet it remains a challenge to identify optimal places in a landscape to direct habitat reconstruction and management. Rather than relying on individual landscape metrics, process-based regional scale assessment methodology is needed that focuses primarily on species persistence. This means integrating, according to species' ecology, habitat extent, suitability, quality and spatial configuration. The rapid evaluation of metapopulation persistence (REMP) methodology has been developed for this purpose. However, till now no practical conservation planning application of REMP has been described. By integration of expert ecological knowledge, we extended REMP's capabilities to prioritize conservation action for a highly modified agricultural region of central NSW, Australia based on the metapopulation ecology of 34 fauna species. The region's current capacity to support the species was evaluated in relation to the pre-European state for which there was known viability. Six of the species were found to currently have insufficient habitat to support viable populations. Seeking locations to maximize overall improvement in viability for these species, we prioritized conservation action to locations near the threshold of metapopulation persistence. PMID- 26902482 TI - Knowledge Co-production at the Research-Practice Interface: Embedded Case Studies from Urban Forestry. AB - Cities are increasingly engaging in sustainability efforts and investment in green infrastructure, including large-scale urban tree planting campaigns. In this context, researchers and practitioners are working jointly to develop applicable knowledge for planning and managing the urban forest. This paper presents three case studies of knowledge co-production in the field of urban forestry in the United States. These cases were selected to span a range of geographic scales and topical scopes; all three are examples of urban researcher practitioner networks in which the authors are situated to comment on reflexively. The three cases resemble institutional structures described in the knowledge co-production literature, including participatory research, a hybrid organization of scientists and managers, and a community of practice. We find that trust, embeddedness, new approaches by both practitioners and researchers, and blending of roles all serve to recognize multiple forms of capability, expertise, and ways of knowing. We discuss the impacts of knowledge co-production and the ways in which hybrid institutional forms can enable its occurrence. PMID- 26902483 TI - Mechanical Fracturing of Core-Shell Undercooled Metal Particles for Heat-Free Soldering. AB - Phase-change materials, such as meta-stable undercooled (supercooled) liquids, have been widely recognized as a suitable route for complex fabrication and engineering. Despite comprehensive studies on the undercooling phenomenon, little progress has been made in the use of undercooled metals, primarily due to low yields and poor stability. This paper reports the use of an extension of droplet emulsion technique (SLICE) to produce undercooled core-shell particles of structure; metal/oxide shell-acetate ('/' = physisorbed, '-' = chemisorbed), from molten Field's metal (Bi-In-Sn) and Bi-Sn alloys. These particles exhibit stability against solidification at ambient conditions. Besides synthesis, we report the use of these undercooled metal, liquid core-shell, particles for heat free joining and manufacturing at ambient conditions. Our approach incorporates gentle etching and/or fracturing of outer oxide-acetate layers through mechanical stressing or shearing, thus initiating a cascade entailing fluid flow with concomitant deformation, combination/alloying, shaping, and solidification. This simple and low cost technique for soldering and fabrication enables formation of complex shapes and joining at the meso- and micro-scale at ambient conditions without heat or electricity. PMID- 26902484 TI - Opportunities for improvement on current nuclear cardiology practices and radiation exposure in Latin America: Findings from the 65-country IAEA Nuclear Cardiology Protocols cross-sectional Study (INCAPS). AB - BACKGROUND: Comparison of Latin American (LA) nuclear cardiology (NC) practice with that in the rest of the world (RoW) will identify areas for improvement and lead to educational activities to reduce radiation exposure from NC. METHODS AND RESULTS: INCAPS collected data on all SPECT and PET procedures performed during a single week in March-April 2013 in 36 laboratories in 10 LA countries (n = 1139), and 272 laboratories in 55 countries in RoW (n = 6772). Eight "best practices" were identified a priori and a radiation-related Quality Index (QI) was devised indicating the number used. Mean radiation effective dose (ED) in LA was higher than in RoW (11.8 vs 9.1 mSv, p < 0.001). Within a populous country like Brazil, a wide variation in laboratory mean ED was found, ranging from 8.4 to 17.8 mSv. Only 11% of LA laboratories achieved median ED <9 mSv, compared to 32% in RoW (p < 0.001). QIs ranged from 2 in a laboratory in Mexico to 7 in a laboratory in Cuba. Three major opportunities to reduce ED for LA patients were identified: (1) more laboratories could implement stress-only imaging, (2) camera-based methods of ED reduction, including prone imaging, could be more frequently used, and (3) injected activity of 99mTc could be adjusted reflecting patient weight/habitus. CONCLUSIONS: On average, radiation dose from NC is higher in LA compared to RoW, with median laboratory ED <9 mSv achieved only one third as frequently as in RoW. Opportunities to reduce radiation exposure in LA have been identified and guideline-based recommendations made to optimize protocols and adhere to the "as low as reasonably achievable" (ALARA) principle. PMID- 26902485 TI - Safety of vasodilator stress myocardial perfusion imaging in patients with elevated cardiac biomarkers. AB - BACKGROUND: While adenosine and dipyridamole as myocardial perfusion imaging (MPI) stress agents have literature supporting their safety in the setting of myocardial infarction (MI), regadenoson does not. Studying a high risk cohort of patients with elevated cardiac biomarkers may shed light on potential safety issues of these agents which might also affect lower risk cohorts. METHODS: All patients who had undergone a clinically indicated stress MPI study at two academic centers from 1/1/2010 through 12/31/2012 with elevated troponin <=7 days prior to testing were included. The primary endpoint was a composite of death, non-fatal MI, congestive heart failure (CHF), stroke, ventricular arrhythmias, atrial fibrillation/flutter, or atrioventricular block requiring intervention within 24 h of testing. RESULTS: Of the 703 stress MPI studies that met inclusion criteria, 360 (51.2%), 199 (28.3%), 74 (10.5%), 9 (1.3%), and 61 (8.7%) underwent regadenoson, dipyridamole, adenosine, dobutamine, and exercise stress, respectively. The primary endpoint occurred in 11 (1.6%) patients with an incidence of 1.4% (n = 5), 1.0% (n = 2), 1.4% (n = 1), 11.1% (n = 1), and 3.3% (n = 2) following regadenoson, dipyridamole, adenosine, dobutamine, and exercise stress, respectively (P = 0.137). The adverse events included non-fatal MI in 7 (1.0%) patients, death in 1 (0.1%) patient, CHF in 1 (0.1%) patient, ventricular arrhythmia in 1 (0.1%) patient, and atrial arrhythmia in 1 (0.1%) patient. CONCLUSION: In the setting of elevated troponin, serious complications associated with either exercise or vasodilator stress testing appear to be relatively rare with no increased risk attributable to a particular vasodilator agent. PMID- 26902487 TI - An oligonucleotide-functionalized carbon nanotube chemiresistor for sensitive detection of mercury in saliva. AB - Divalent mercuric (Hg(2+)) ion and monomethyl mercury (CH3Hg(+)) are two forms of mercury that are known to be highly toxic to humans. In this work, we present a highly selective, sensitive and label-free chemiresistive biosensor for the detection of both, Hg(2+) and CH3Hg(+) ions using DNA-functionalized single walled carbon nanotubes (SWNTs). The SWNTs were functionalized with the capture oligonucleotide, polyT, using a linker molecule. The polyT was hybridized with polyA to form a polyT:polyA duplex. Upon exposure to mercury ions, the polyT:polyA duplex dehybridizes and a T-Hg(2+)-T duplex is formed. This structure switch leads to the release of polyA from the SWNT surface and correspondingly a change in the resistance of the chemiresistive biosensor is observed, which is used to quantify the mercury ion concentration. The biosensor showed a wide dynamic range of 0.5 to 100 nM for the detection of CH3Hg(+) ions in buffer solution with a sensitivity of 28.34% per log (nM) of CH3Hg(+). Finally, real world application of the biosensor was demonstrated by the detection of Hg(2+) and CH3Hg(+) ions in simulated saliva samples spiked with a known concentration of mercury ions. PMID- 26902486 TI - Plasmodium falciparum PfSET7: enzymatic characterization and cellular localization of a novel protein methyltransferase in sporozoite, liver and erythrocytic stage parasites. AB - Epigenetic control via reversible histone methylation regulates transcriptional activation throughout the malaria parasite genome, controls the repression of multi-copy virulence gene families and determines sexual stage commitment. Plasmodium falciparum encodes ten predicted SET domain-containing protein methyltransferases, six of which have been shown to be refractory to knock-out in blood stage parasites. We have expressed and purified the first recombinant malaria methyltransferase in sufficient quantities to perform a full enzymatic characterization and reveal the ill-defined PfSET7 is an AdoMet-dependent histone H3 lysine methyltransferase with highest activity towards lysines 4 and 9. Steady state kinetics of the PfSET7 enzyme are similar to previously characterized histone methyltransferase enzymes from other organisms, however, PfSET7 displays specific protein substrate preference towards nucleosomes with pre-existing histone H3 lysine 14 acetylation. Interestingly, PfSET7 localizes to distinct cytoplasmic foci adjacent to the nucleus in erythrocytic and liver stage parasites, and throughout the cytoplasm in salivary gland sporozoites. Characterized recombinant PfSET7 now allows for target based inhibitor discovery. Specific PfSET7 inhibitors can aid in further investigating the biological role of this specific methyltransferase in transmission, hepatic and blood stage parasites, and may ultimately lead to the development of suitable antimalarial drug candidates against this novel class of essential parasite enzymes. PMID- 26902488 TI - Persistent Maternal Cardiac Dysfunction After Preeclampsia Identifies Patients at Risk for Recurrent Preeclampsia. AB - The purpose of our study was to assess cardiac function in nonpregnant women with previous early preeclampsia before a second pregnancy to highlight the cardiovascular pattern, which may take a risk for recurrent preeclampsia. Seventy five normotensive patients with previous preeclampsia and 147 controls with a previous uneventful pregnancy were enrolled in a case-control study and submitted to echocardiographic examination in the nonpregnant state 12 to 18 months after the first delivery. All patients included in the study had pregnancy within 24 months from the echocardiographic examination and were followed until term. Twenty-two (29%) of the 75 patients developed recurrent preeclampsia. In the nonpregnant state, patients with recurrent preeclampsia compared with controls and nonrecurrent preeclampsia had lower stroke volume (63 +/- 14 mL versus 73 +/- 12 mL and 70 +/- 11 mL, P<0.05), cardiac output (4.6 +/- 1.2 L versus 5.3 +/- 0.9 L and 5.2 +/- 1.0 L, P<0.05), higher E/E' ratio (11.02 +/- 3.43 versus 7.34 +/- 2.11 versus 9.03 +/- 3.43, P<0.05), and higher total vascular resistance (1638 +/ 261 dyne . s(-1) . cm(-5) versus 1341 +/- 270 dyne . s(-1) . cm(-5) and 1383 +/- 261 dyne . s(-1) . cm(-5), P<0.05). Left ventricular mass index was higher in both recurrent and nonrecurrent preeclampsia compared with controls (30.0 +/- 6.3 g/m(2.7) and 30.4 +/- 6.8 g/m(2.7) versus 24.8 +/- 5.0 g/m(2.7), P<0.05). Signs of diastolic dysfunction and different left ventricular characteristics are present in the nonpregnant state before a second pregnancy with recurrent preeclampsia. Previous preeclamptic patients with nonrecurrent preeclampsia show left ventricular structural and functional features intermediate with respect to controls and recurrent preeclampsia. PMID- 26902489 TI - Echoes of Preeclampsia: Can Echocardiography Help Predict Recurrence? PMID- 26902490 TI - Introduction to the American Heart Association's Hypertension Strategically Focused Research Network. PMID- 26902491 TI - Effects of Baroreflex Activation Therapy on Ambulatory Blood Pressure in Patients With Resistant Hypertension. AB - Baroreflex activation therapy (BAT) has been demonstrated to decrease office blood pressure (BP) in the randomized, double-blind Rheos trial. There are limited data on 24-hour BP changes measured by ambulatory BP measurements (ABPMs) using the first generation rheos BAT system suggesting a significant reduction but there are no information about the effect of the currently used, unilateral BAT neo device on ABPM. Patients treated with the BAT neo device for uncontrolled resistant hypertension were prospectively included into this study. ABPM was performed before BAT implantation and 6 months after initiation of BAT. A total of 51 patients were included into this study, 7 dropped out from analysis because of missing or insufficient follow-up. After 6 months, 24-hour ambulatory systolic (from 148 +/- 17 mm Hg to 140 +/- 23 mm Hg, P<0.01), diastolic (from 82 +/- 13 mm Hg to 77 +/- 15 mm Hg, P<0.01), day- and night-time systolic and diastolic BP (all P <= 0.01) significantly decreased while the number of prescribed antihypertensive classes could be reduced from 6.5 +/- 1.5 to 6.0 +/- 1.8 (P=0.03). Heart rate and pulse pressure remained unchanged. BAT was equally effective in reducing ambulatory BP in all subgroups of patients. This is the first study demonstrating a significant BP reduction in ABPM in patients undergoing chronically stimulation of the carotid sinus using the BAT neo device. About that BAT-reduced office BP and improved relevant aspects of ABPM, BAT might be considered as a new therapeutic option to reduce cardiovascular risk in patients with resistant hypertension. Randomized controlled trials are needed to evaluate BAT effects on ABPM in patients with resistant hypertension accurately. PMID- 26902492 TI - Effects of Different Dietary Interventions on Blood Pressure: Systematic Review and Meta-Analysis of Randomized Controlled Trials. AB - Previous studies have shown beneficial effects of individual dietary approaches for blood pressure (BP) control, but their relative effectiveness is not well established. We performed a systematic review of published dietary pattern interventions and estimated the aggregate BP effects through meta-analysis. PubMed, EMBASE, and Web of Science databases were searched to identify studies published between January 1, 1990 and March 1, 2015. Studies meeting specific inclusion and exclusion criteria were selected. Data were pooled using random effects meta-analysis models. Twenty-four trials with 23 858 total participants were included. The overall pooled net effect of dietary intervention on systolic BP and diastolic BP was -3.07 mm Hg (95% confidence interval, -3.85 to -2.30) and -1.81 mm Hg (95% confidence interval, -2.24 to -1.38), respectively. The Dietary Approaches to Stop Hypertension diet had the largest net effect (systolic BP, 7.62 mm Hg [95% confidence interval, -9.95 to -5.29] and diastolic BP, -4.22 mm Hg [95% confidence interval, -5.87 to -2.57]). Low-sodium; low-sodium, high potassium; low-sodium, low-calorie; and low-calorie diets also led to significant systolic and diastolic BP reductions, whereas Mediterranean diet participants experienced a significant incremental reduction in diastolic but not systolic BP. Subgroup analysis also showed important variations in effectiveness based on duration, size, and participant demographics. In conclusion, dietary modifications are associated with clinically meaningful, though variable, reductions in BP. Some diets are more effective than others and under different circumstances, which has important implications from both clinical and public health perspectives. PMID- 26902493 TI - Vascular Smooth Muscle Mineralocorticoid Receptor Contributes to Coronary and Left Ventricular Dysfunction After Myocardial Infarction. AB - Mineralocorticoid receptor (MR) antagonists slow down the progression of heart failure after myocardial infarction (MI), but the cell-specific role of MR in these benefits is unclear. In this study, the role of MR expressed in vascular smooth muscle cells (VSMCs) was investigated. Two months after coronary artery ligation causing MI, mice with VSMC-specific MR deletion (MI-MR(SMKO)) and mice treated with the MR antagonist finerenone (MI-fine) had improved left ventricular compliance and elastance when compared with infarcted control mice (MI-CTL), as well as reduced interstitial fibrosis. Importantly, the coronary reserve assessed by magnetic resonance imaging was preserved (difference in myocardial perfusion before and after induction of vasodilatation, mL mg(-1) min(-1): MI-CTL: 1.1 +/- 0.5, nonsignificant; MI-MR(SMKO): 4.6 +/- 1.6 [P<0.05]; MI-fine: 3.6 +/- 0.7 [P<0.01]). The endothelial function, tested on isolated septal coronary arteries by analyzing the acetylcholine-induced nitric oxide-dependent relaxation, was also improved by MR deletion in VSMCs or by finerenone treatment (relaxation %: MI-CTL: 36 +/- 5, MI-MR(SMKO): 54 +/- 3, and MI-fine: 76 +/- 4; P<0.05). Such impairment of the coronary endothelial function on MI involved an oxidative stress that was reduced when MR was deleted in VSMCs or by finerenone treatment. Moreover, short-term incubation of coronary arteries isolated from noninfarcted animals with low-dose angiotensin-II (10(-9) mol/L) induced oxidative stress and impaired acetylcholine-induced relaxation in CTL but neither in MR(SMKO) nor in mice pretreated with finerenone. In conclusion, deletion of MR in VSMCs improved left ventricular dysfunction after MI, likely through maintenance of the coronary reserve and improvement of coronary endothelial function. MR blockage by finerenone had similar effects. PMID- 26902494 TI - Common Polymorphisms at the CYP17A1 Locus Associate With Steroid Phenotype: Support for Blood Pressure Genome-Wide Association Study Signals at This Locus. AB - Genome-wide association studies implicate the CYP17A1 gene in human blood pressure regulation although the causative polymorphisms are as yet unknown. We sought to identify common polymorphisms likely to explain this association. We sequenced the CYP17A1 locus in 60 normotensive individuals and observed 24 previously identified single-nucleotide polymorphisms with minor allele frequency >0.05. From these, we selected, for further studies, 7 polymorphisms located <= 2 kb upstream of the CYP17A1 transcription start site. In vitro reporter gene assays identified 3 of these (rs138009835, rs2150927, and rs2486758) as having significant functional effects. We then analyzed the association between the 7 polymorphisms and the urinary steroid metabolites in a hypertensive cohort (n=232). Significant associations included that of rs138009835 with aldosterone metabolite excretion; rs2150927 associated with the ratio of tetrahydrodeoxycorticosterone to tetrahydrodeoxycortisol, which we used as an index of 17alpha-hydroxylation. Linkage analysis showed rs138009835 to be the only 1 of the 7 polymorphisms in strong linkage disequilibrium with the blood pressure-associated polymorphisms identified in the previous studies. In conclusion, we have identified, characterized, and investigated common polymorphisms at the CYP17A1 locus that have functional effects on gene transcription in vitro and associate with corticosteroid phenotype in vivo. Of these, rs138009835--which we associate with changes in aldosterone level--is in strong linkage disequilibrium with polymorphisms linked by genome-wide association studies to blood pressure regulation. This finding clearly has implications for the development of high blood pressure in a large proportion of the population and justifies further investigation of rs138009835 and its effects. PMID- 26902495 TI - Prognostic Effect of the Nocturnal Blood Pressure Fall in Hypertensive Patients: The Ambulatory Blood Pressure Collaboration in Patients With Hypertension (ABC-H) Meta-Analysis. AB - The prognostic importance of the nocturnal systolic blood pressure (SBP) fall, adjusted for average 24-hour SBP levels, is unclear. The Ambulatory Blood Pressure Collaboration in Patients With Hypertension (ABC-H) examined this issue in a meta-analysis of 17 312 hypertensives from 3 continents. Risks were computed for the systolic night-to-day ratio and for different dipping patterns (extreme, reduced, and reverse dippers) relative to normal dippers. ABC-H investigators provided multivariate adjusted hazard ratios (HRs), with and without adjustment for 24-hour SBP, for total cardiovascular events (CVEs), coronary events, strokes, cardiovascular mortality, and total mortality. Average 24-hour SBP varied from 131 to 140 mm Hg and systolic night-to-day ratio from 0.88 to 0.93. There were 1769 total CVEs, 916 coronary events, 698 strokes, 450 cardiovascular deaths, and 903 total deaths. After adjustment for 24-hour SBP, the systolic night-to-day ratio predicted all outcomes: from a 1-SD increase, summary HRs were 1.12 to 1.23. Reverse dipping also predicted all end points: HRs were 1.57 to 1.89. Reduced dippers, relative to normal dippers, had a significant 27% higher risk for total CVEs. Risks for extreme dippers were significantly influenced by antihypertensive treatment (P<0.001): untreated patients had increased risk of total CVEs (HR, 1.92), whereas treated patients had borderline lower risk (HR, 0.72) than normal dippers. For CVEs, heterogeneity was low for systolic night-to day ratio and reverse/reduced dipping and moderate for extreme dippers. Quality of included studies was moderate to high, and publication bias was undetectable. In conclusion, in this largest meta-analysis of hypertensive patients, the nocturnal BP fall provided substantial prognostic information, independent of 24 hour SBP levels. PMID- 26902496 TI - CNQX facilitates inhibitory synaptic transmission in rat hypoglossal nucleus. AB - 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX) is a most commonly used antagonist of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor in the central nervous system. During the past two decades, studies had demonstrated that CNQX could partially activate AMPA receptors that are located on the hippocampal and cerebellar interneurons, thus subsequently leading to the facilitation of inhibitory transmission. However, whether CNQX could enhance inhibitory synaptic transmission in the hypoglossal nucleus remains elusive. Here, using whole-cell patch-clamp recording in the brainstem slice, we showed that CNQX greatly increased both frequency and amplitude of spontaneous inhibitory postsynaptic currents in the hypoglossal motoneurons, whereas D-(-)-2 Amino-5-phosphonopentanoic acid (D-AP5), N-methyl-D-aspartate (NMDA) receptor antagonist, had no effect on inhibitory synaptic transmission. Application of bicuculline and strychnine further identified that CNQX not only increased GABAergic sIPSCs but also glycinergic one in these motoneurons. Similar enhancement of inhibitory transmission was observed with application of 6, 7 dinitroquinoxaline-2, 3-dione (DNQX), a quinoxaline derivative of CNQX, but not with application of GYKI 53655, a non-competitive antagonist of AMPA receptor. In the presence of tetradotoxin, the effect of CNQX on sIPSCs was abolished, suggesting that an increase in presynaptic interneuron spike firing rate induced by CNQX was responsible for the facilitation of sIPSCs. Taken together, these results demonstrated that the excitatory effect of CNQX on presynaptic interneurons triggered enhancement of both GABAergic and glycinergic synaptic transmission within the rat hypoglossal nucleus. PMID- 26902497 TI - TBPH/TDP-43 modulates translation of Drosophila futsch mRNA through an UG-rich sequence within its 5'UTR. AB - Nuclear factor TDP-43 is an evolutionarily conserved multifunctional RNA-binding protein associated with frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). In recent years, Drosophila models of ALS based on TDP 43 knockdown/overexpression have allowed to find several connections with disease. Among these, we have previously described that silencing the expression of its fly ortholog (TBPH) can alter the expression of the neuronal microtubule associated protein Futsch leading to alterations of neuromuscular junction (NMJ) organization. In particular, TBPH knocked out flies displayed a significant reduction of Futsch protein levels, although minimal variation in the futsch mRNA content was observed. These conclusions were recently validated in an independent study. Together, these observations strongly support the hypothesis that TBPH might regulate the translation of futsch mRNA. However, the mechanism of TBPH interference in futsch mRNA translation is still unknown. In this work, we use EMSA experiments coupled with RNA-protein co-immunprecipitations and luciferase assays to show that TBPH interacts with a stretch of UG within the 5'UTR of futsch mRNA and translation is positively modulated by this binding. Most importantly, this function is also conserved in human TDP-43. This result can therefore represent the first step in elucidating the relationship between TDP 43, protein translation, and eventual disease onset or progression. This article is part of a Special Issue entitled SI:RNA Metabolism in Disease. PMID- 26902500 TI - Through Their Words: Sources of Bother for Hospitalized Children and Adolescents With Cancer. AB - An increased intensity of inpatient treatment, hospital-based routines, and separation from the familiar home environment may collectively increase the burden of the pediatric cancer experience. This study explored children and adolescents' perceived sources of bother related to hospitalization using two questions: (1) What bothered you the most about the hospital or hospital environment? and (2) What do you think could improve the hospital or hospital environment? Fifty children and adolescents (mean age 12.6 years) responded to these questions during each shift of a 3-day/3-night data collection period. Responses were analyzed using content analysis and chi-square analyses. Themes related to sources of bother included (1) "nothing/don't know," (2) "treatment and its consequences," (3) "isolation and loneliness," (4) "imposed bother," (5) "negative environment," and (6) "staff behaviors." Themes related to improving the hospital environment included (1) "nothing/don't know," (2) "normalizing activities," (3) "quality of the hospital environment," (4) "decrease burden of cancer and its treatment," and (5) "patient care issues." Participants' responses to these questions provide a foundation for actionable change to alleviate the burden associated with hospitalization. PMID- 26902499 TI - Evaluation of Pre-Hematopoietic Cell Transplantation (HCT) Brain MRI and Neurologic Complications of Pediatric Patients Undergoing HCT for Hematologic Malignancies. AB - Adverse neurologic complications (NC) occur commonly in pediatric patients with hematologic malignancies both pre- and post-allogeneic hematopoietic cell transplant (HCT). Given this known risk, we previously obtained pre-HCT brain magnetic resonance imaging (MRI) to document baseline abnormalities but utility of this and findings are not well described. This study aimed to ( a) determine the prevalence and risk factors for abnormal brain MRI and ( b) determine prevalence and risk factors for development of new NC during and 2 years post HCT. Retrospective chart review included 102 patients with hematologic malignancies who underwent allogeneic HCT between 2000 and 2009 at University of California San Francisco (UCSF) Children's Hospital and included standard HCT data, brain MRI reports, and NC and symptoms pre- and post-HCT. Forty-three percent of patients had abnormal findings on pre-MRI, most commonly nonspecific white matter changes. Neurologic symptoms pre-HCT was the only significant risk factor for abnormal MRI. Eleven patients (11%) developed post-HCT NC. Non Caucasian race was the only significant risk factor for new NC. Although abnormal pre-HCT brain MRI is common, these findings are not predictive of subsequent NC post-HCT. Therefore routine surveillance may not be informative for that purpose, particularly when general anesthesia is required, which can have detrimental neurocognitive effects. Etiology of NC in pediatric HCT is likely multifactorial and may include genetic and ethnic predispositions. PMID- 26902498 TI - Pygo2 functions as a prognostic factor for glioma due to its up-regulation of H3K4me3 and promotion of MLL1/MLL2 complex recruitment. AB - Pygo2 has been discovered as an important Wnt signaling component contributing to the activation of Wnt-target gene transcription. In the present study, we discovered that Pygo2 mRNA and protein levels were up-regulated in the majority of (152/209) human brain glioma tissues and five glioma cell lines, and significantly correlated with the age, the WHO tumor classification and poor patient survival. The histone methyltransferase complex components (WDR5, Ash2, and menin, but not CXCC1 or NCOA6) were down-regulated at the promoter loci of Wnt target genes after Pygo2 knockdown, and this was accompanied by the down regulation of Wnt/beta-catenin pathway activity. Further, we demonstrated that the involvement of Pygo2 in the activation of the Wnt pathway in human glioma progression is through up-regulation of the H3K4me3 (but not H3K4me2) by promoting the recruitment of the histone methyltransferase MLL1/MLL2 complex to Wnt target gene promoters. Thus, our study provided evidence that Pygo2 functions as a novel prognostic marker and represents a potential therapeutic target. PMID- 26902501 TI - Perceptions of a Primary Nursing Care Model in a Pediatric Hematology/Oncology Unit. AB - The primary nursing care model optimizes relationship-based care. Despite using a primary nursing model on a pediatric hematology/oncology inpatient unit, it was hypothesized patients and nurses were dissatisfied with the structure of primary care teams and inconsistency of primary assignments. The purpose of this study was to evaluate patient/family and nurse perceptions of our current care model through assessing gaps in its operationalization and satisfaction. This study used a descriptive cross-sectional design featuring patient/family and nurse surveys. Of the 59 patient/family respondents, 93.2% prefer to have a primary nurse care for them and 85% are satisfied with how often they are assigned a primary care team member. Similarly, 63% of the 57 nurse respondents are satisfied with the current implementation of our primary nursing model and 61% state the model reflects good continuity of care. Yet 80.7% of nurses believe safety would improve for a patient whose nurse works shifts consecutively even if not a primary nurse. Overall, patients, families, and nurses value care continuity and meaningful nurse-patient relationships, which is fundamental to primary nursing. PMID- 26902502 TI - BK Virus-Associated Hemorrhagic Cystitis After Allogeneic Hematopoietic Stem Cell Transplantation in the Pediatric Population. AB - OBJECTIVE: To study the incidence, risk factors, and treatment of hemorrhagic cystitis secondary to BK-virus reactivation (HC-BKV) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the pediatric population. METHODS: Case-control study in which all pediatric patients (0-18 years) who underwent allo-HSCT from September 2009 to January 2014 were followed. RESULTS: Twenty-nine patients underwent an allo-HSCT. The median age was 9 years (range = 6 months to 15 years), 61% male. The primary diagnosis was acute lymphoblastic leukemia (72.4%). Six (20.7%) developed HC-BKV. In a multivariate analysis of risk factors, it was observed that the reactivation of BK virus was associated with age more than 10 years ( P = .098) and those with positive serology for Epstein-Barr virus ( P = .06). Five of the 6 patients with HC-BKV received cidofovir (CDV) at doses of 3 to 5 mg/kg/week. The treatment lasted a median of 3 cycles (range = 2-5). One of the patients (20%) developed nephrotoxicity. Of the 5 patients treated with CDV, 3 (60%) had a complete response, 1 (20%) partial response, and 1 (20%) no response. CONCLUSION: We conclude that HC-BKV is a frequent complication after allo-HSCT. CDV therapy can be effective but controlled clinical trials are needed. PMID- 26902504 TI - Population pharmacokinetics of inhaled fluticasone furoate and vilanterol in adult and adolescent patients with asthma. AB - OBJECTIVES: Population pharmacokinetic (PK) methods were used to characterize the PK of fluticasone furoate (FF) and vilanterol (VI) in patients with asthma following once daily inhaled FF/VI and FF and to identify significant covariates that impact the PK. MATERIALS AND METHODS: Four of the five studies in the meta analysis were conducted in patients with asthma (> 90%), the fifth in healthy subjects. FF data were described by a two-compartment model with first order absorption and elimination. VI data were described by a three-compartment model with zero-order absorption and first order elimination. RESULTS: Race was a significant covariate on inhaled clearance (CL/F) of FF PK. AUC(0-24) for Asian patients was on average 33 - 53% higher than for non-Asians. Race was also a significant covariate on VI PK, with lower (81%) central volume of distribution (Vc/F) for Asian patients compared with non-Asians; VI C(max) was 220 - 287% higher in Asian patients. Treatment (combination or monotherapy), predicted percentage FEV(1), and other demographic variables did not influence the PK of FF or VI. CONCLUSIONS: Combination of FF/VI does not appear to affect the PK of FF or VI. The effect of race on PK of FF or VI does not have impact on dosage adjustments for FF/VI in East Asian patients with asthma. PMID- 26902503 TI - Alternative methods for CYP2D6 phenotyping: comparison of dextromethorphan metabolic ratios from AUC, single point plasma, and urine. AB - PURPOSE: CYP2D6 is a high polymorphic enzyme. Determining its phenotype before CYP2D6 substrate treatment can avoid dose-dependent adverse events or therapeutic failures. Alternative phenotyping methods of CYP2D6 were compared to aluate the appropriate and precise time points for phenotyping after single-dose and ultiple dose of 30-mg controlled-release (CR) dextromethorphan (DM) and to explore the antimodes for potential sampling methods. METHODS: This was an open-label, single and multiple-dose study. 21 subjects were assigned to receive a single dose of CR DM 30 mg orally, followed by a 3-day washout period prior to oral administration of CR DM 30 mg every 12 hours for 6 days. Metabolic ratios (MRs) from AUCinfinity after single dosing and from AUC0-12h at steady state were taken as the gold standard. The correlations of metabolic ratios of DM to dextrorphan (MRDM/DX) values based on different phenotyping methods were assessed. Linear regression formulas were derived to calculate the antimodes for potential sample methods. RESULTS: In the single-dose part of the study statistically significant correlations were found between MRDM/DX from AUCinfinity and from serial plasma points from 1 to 30 hours or from urine (all p-values < 0.001). In the multiple dose part, statistically significant correlations were found between MRDM/DX from AUC0-12h on day 6 and MRDM/DX from serial plasma points from 0 to 36 hours after the last dosing (all p-values < 0.001). Based on reported urinary antimode and linear regression analysis, the antimodes of AUC and plasma points were derived to profile the trend of antimodes as the drug concentrations changed. CONCLUSION: MRDM/DX from plasma points had good correlations with MRDM/DX from AUC. Plasma points from 1 to 30 hours after single dose of 30-mg CR DM and any plasma point at steady state after multiple doses of CR DM could potentially be used for phenotyping of CYP2D6. PMID- 26902505 TI - Antifungal effects of undecylenic acid on the biofilm formation of Candida albicans. AB - Undecylenic acid can effectively control skin fungal infection, but the mechanism of its fungal inhibition is unclear. Hyphal growth of Candida albicans (C. albicans) and biofilm formation have been well recognized as important virulence factors for the initiation of skin infection and late development of disseminated infection. In this study, we seek to investigate antifungal mechanisms of undecylenic acid by evaluating the virulence factors of C. albicans during biofilm formation. We found that undecylenic acid inhibits biofilm formation of C. albicans effectively with optimal concentration above 3 mM. In the presence of this compound, the morphological transition from yeast to filamentous phase is abolished ultimately when the concentration of undecylenic acid is above 4 mM. Meanwhile, the cell surface is crumpled, and cells display an atrophic appearance under scanning electron microscopy even with low concentration of drug treatment. On the other hand, the drug treatment decreases the transcriptions of hydrolytic enzymes such as secreted aspartic protease, lipase, and phospholipase. Hyphal formation related genes, like HWP1, are significantly reduced in transcriptional level in drug-treated biofilm condition as well. The down-regulated profile of these genes leads to a poorly organized biofilm in undecylenic acid treated environment. PMID- 26902506 TI - Population pharmacokinetics of aripiprazole in healthy Korean subjects. AB - OBJECTIVE: Aripiprazole is widely used to treat schizophrenia and bipolar disorder. This study aimed to develop a combined population pharmacokinetic model for aripiprazole in healthy Korean subjects and to identify the significant covariates in the pharmacokinetic variability of aripiprazole. METHODS: Aripiprazole plasma concentrations and demographic data were collected retrospectively from previous bioequivalence studies that were conducted in Chonbuk National University Hospital. Informed consent was obtained from subjects for cytochrome P450 (CYP) genotyping. The population pharmacokinetic parameters of aripiprazole were estimated using nonlinear mixed-effect modeling with first order conditional estimation with interaction method. The effects of age, sex, weight, height, and CYP genotype were assessed as covariates. RESULTS: A total of 1,508 samples from 88 subjects in three bioequivalence studies were collected. The two-compartment model was adopted, and the final population model showed that the CYP2D6 genotype polymorphism, height and weight significantly affect aripiprazole disposition. The bootstrap and visual predictive check results were evaluated, showing that the accuracy of the pharmacokinetic model was acceptable. CONCLUSIONS: A population pharmacokinetic model of aripiprazole was developed for Korean subjects. CYP2D6 genotype polymorphism, weight, and height were included as significant factors affecting aripiprazole disposition. The population pharmacokinetic parameters of aripiprazole estimated in the present study may be useful for individualizing clinical dosages and for studying the concentration effect relationship of the drug. PMID- 26902507 TI - Effects of vitamin D on blood pressure in patients with type 2 diabetes mellitus. AB - PURPOSE: Previous studies have suggested that vitamin D supplementation may decrease blood pressure in patients with type 2 diabetes, although conflicting results have been reported. The purpose of this meta-analysis was to evaluate the effects of the vitamin D supplementation on blood pressure in patients with type 2 diabetes. METHODS: A meta-analysis of published randomized controlled trials was conducted. Eligible studies were identified via a literature search of the MEDLINE (PubMed), EMBASE, and Cochrane Library databases through to May 25, 2015. The endpoint of the analysis was the change in blood pressure due to vitamin D treatment in patients with type 2 diabetes. These changes were calculated as the difference between the baseline and final measurements performed in each study. A fixed-effects model was used to calculate the combined effect estimates; in the presence of heterogeneity, a random-effects model was used. RESULTS: A total of 15 articles were included in the meta-analysis. All 15 articles, including 1,134 patients with type 2 diabetes, were analyzed for systolic blood pressure (SBP), and 13 articles, including 793 patients, were analyzed for diastolic blood pressure (DBP). The combined-effect estimate of vitamin D intervention on SBP was -0.121 mmHg (95% confidence interval (CI) -0.355 to 0.113, p = 0.311), and considerable heterogeneity was observed between studies (p < 0.001, I(2)= 74.2%). For DBP, the combined effect estimate was -0.160 mmHg (95% CI -0.298 to -0.022, p = 0.023), and no heterigenieity was observed (p = 0.673, I(2) = 0.0%). CONCLUSIONS: This study is the first meta-analysis of the effect of vitamin D supplementation on blood pressure in patients with type 2 diabetes. This meta analysis demonstrated that vitamin D supplementation may result in a reduction in DBP in patients with type 2 diabetes. However, additional studies with large sample sizes and longer durations are needed to establish a relationship between vitamin D and blood pressure in patients with type 2 diabetes. PMID- 26902508 TI - The mitochondrial permeability transition pore in AD 2016: An update. AB - Over the past 30years the mitochondrial permeability transition - the permeabilization of the inner mitochondrial membrane due to the opening of a wide pore - has progressed from being considered a curious artifact induced in isolated mitochondria by Ca(2+) and phosphate to a key cell-death-inducing process in several major pathologies. Its relevance is by now universally acknowledged and a pharmacology targeting the phenomenon is being developed. The molecular nature of the pore remains to this day uncertain, but progress has recently been made with the identification of the FOF1 ATP synthase as the probable proteic substrate. Researchers sharing this conviction are however divided into two camps: these believing that only the ATP synthase dimers or oligomers can form the pore, presumably in the contact region between monomers, and those who consider that the ring-forming c subunits in the FO sector actually constitute the walls of the pore. The latest development is the emergence of a new candidate: Spastic Paraplegia 7 (SPG7), a mitochondrial AAA-type membrane protease which forms a 6-stave barrel. This review summarizes recent developments of research on the pathophysiological relevance and on the molecular nature of the mitochondrial permeability transition pore. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and Jean-Claude Martinou. PMID- 26902510 TI - What next for the junior doctor contract? PMID- 26902511 TI - Influence of local habitat on the physiological responses of large benthic foraminifera to temperature and nutrient stress. AB - Large benthic foraminifera (LBF) are important for reef sediment formation, but sensitive to elevated temperature and nutrients. However, it is possible that conspecific foraminifera living in different reef sites present divergent response to environmental shifts. We investigated how populations of Amphistegina lobifera from reef sites located along a temperature and nutrient gradient of the northern Great Barrier Reef respond and acclimate to elevated temperature and nitrate under lab-controlled conditions. Generalized linear mixed models showed that interaction between reef sites and temperature or nitrate conditions had a significant effect on survivorship, bleaching frequency and growth rates of A. lobifera. Further physiological analyses of antioxidant capacity and Ca-ATPase activity showed that populations collected from the inner-shelf sites (highest nutrient levels, largest temperature variation) were consistently able to acclimate to both parameters after 30 days. In contrast, foraminifera collected from the reef sites located in the mid- and outer-shelfs were significantly more sensitive to elevated temperatures and nitrate. Our results highlight the importance of local habitat in shaping the tolerance of LBF to changing environmental conditions; populations that live in stable environments are more sensitive to elevated temperature and nitrate, even within their fundamental tolerance range, than those that experience fluctuating conditions. PMID- 26902513 TI - Transmembrane voltage: Potential to induce lateral microdomains. AB - Lateral segregation of plasma membrane lipids is a generally accepted phenomenon. Lateral lipid microdomains of specific composition, structure and biological functions are established as a result of simultaneous action of several competing mechanisms which contribute to membrane organization. Various lines of evidence support the conclusion that among those mechanisms, the membrane potential plays significant and to some extent unique role. Above all, clear differences in the microdomain structure as revealed by fluorescence microscopy could be recognized between polarized and depolarized membranes. In addition, recent fluorescence spectroscopy experiments reported depolarization-induced changes in a membrane lipid order. In the context of earlier findings showing that plasma membranes of depolarized cells are less susceptible to detergents and the cells less sensitive to antibiotics or antimycotics treatment we discuss a model, in which membrane potential-driven re-organization of the microdomain structure contributes to maintaining membrane integrity during response to stress, pathogen attack and other challenges involving partial depolarization of the plasma membrane. This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon. PMID- 26902509 TI - The genome of the miiuy croaker reveals well-developed innate immune and sensory systems. AB - The miiuy croaker, Miichthys miiuy, is a representative Sciaenidae known for its exceptionally large otoliths. This species mainly inhabits turbid aquatic environments with mud to sandy mud bottoms. However, the characteristics of the immune system of this organism and its specific aquatic environment adaptations are poorly understood. Thus, we present a high-quality draft genome of miiuy croaker. The expansions of several gene families which are critical for the fish innate immune system were identified. Compared with the genomes of other fishes, some changes have occurred in the miiuy croaker sensory system including modification of vision and expansion of taste and olfaction receptors. These changes allow miiuy croaker to adapt to the environment during the long-term natural selection. The genome of miiuy croaker may elucidate its relatively well developed immune defense and provide an adaptation model of the species thriving in turbid deep aquatic environments. PMID- 26902514 TI - Predicted superconductivity of Ni2VAl and pressure dependence of superconductivity in Ni2NbX (X = Al, Ga and Sn) and Ni2VAl. AB - A first-principles study of the electronic and superconducting properties of the Ni2VAl Heusler compound is presented. The electron-phonon coupling constant of lambda(ep)=0.68 is obtained, which leads to a superconducting transition temperature of Tc = ~ 4K (assuming a Coulomb pseudopotential MU(*)=0.13), which is a relatively high transition temperature for Ni based Heusler alloys. The electronic density of states reveals a significant hybridization between Ni-eg and V-t(2g) states around the Fermi level. The Fermi surface, consisting of two electron pockets around the X-points of the Brillouin zone, exhibits nesting and leads to a Kohn anomaly of the phonon dispersion relation for the transverse acoustic mode TA2 along the (1, 1, 0) direction, which is furthermore found to soften with pressure. As a consequence, T(c) and lambda(ep) vary non monotonically under pressure. The calculations are compared to similar calculations performed for the Ni2NbX (X = Al, Ga and Sn) Heusler alloys, which experimentally have been identified as superconductors. The experimental trend in T(c) is well reproduced, and reasonable quantitative agreement is obtained. The calculated T(c) of Ni2VAl is larger than either calculated or observed T(c)s of any of the Nb compounds. The Fermi surfaces of Ni2NbAl and Ni2NbGa consist of only a single electron pocket around the X point, however under compression a second electron pocket similar to that of Ni2VAl emerges Ni2NbAl and the T(c) increases non-monotonically in all the compounds. Fermi surface nesting and associated Kohn anomalies are a common feature of all four compounds, albeit weakest in Ni2VAl. PMID- 26902512 TI - Lower urinary tract symptoms in children with anorectal malformations with rectoperineal fistulas. AB - AIM: The aim was to describe the frequency of lower urinary tract symptoms (LUTS) in children with anorectal malformations with rectoperineal fistulas (ARM-P), as compared with healthy controls based on gender. METHOD: LUTS were defined using the 2014 definitions of the International Children's Continence Society. Data were collected at 2 tertiary pediatric surgery centers in 2 countries from all children aged 4-12years who had undergone an operation for ARM-P. RESULTS: A total of 24 girls and 33 boys, with a median age of 8 (4-12)years, were eligible and compared with 165 controls. Of the patient group, 4 (17%) girls had 8 urinary tract anomalies (UTA), and 8 (24%) boys had 13 UTA. There were no gender differences in LUTS among the patients. The frequency of urinary tract infections was higher among the patients (5/24 girls and 7/55 boys) than the controls (1/55 and 4/110) (p=0.009). More patients (5/24 girls and 5/33 boys) than controls (1/55 and 2/110) used daily urinary medications (p=0.009 and p=0.007, respectively). Patients with UTA reported urinary infections more frequently (3/4 girls and 4/8 boys) than those without UTA (2/20 girls and 0/25 boys) (p=0.018 and p=0.002, respectively). CONCLUSION: Children with ARM-P had more LUTS than controls, and patients with concomitant UTA had more LUTS than patients without UTA. Therefore, children with ARM-P are suggested to have routine follow-up for both UTA and LUTS. PMID- 26902515 TI - Developmental change in the contribution of voltage-gated Ca(2+) channels to the pacemaking of deep cerebellar nuclei neurons. AB - The activity of the deep cerebellar nuclei (DCN) neurons conveys the bulk of the output of the cerebellum. To generate these motor signals, DCN neurons integrate synaptic inputs with their own spontaneous activity. We have previously reported that N-type voltage-gated Ca(2+) channels modulate the spontaneous activity of the majority of juvenile DCN neurons in vitro. Specifically, pharmacologically blocking N-type Ca(2+) channels increases their firing rate causing DCN cells to burst. Adult DCN neurons however, behaved differently. To further investigate this change, we have studied here the effect of cadmium on the firing rate of DCN neurons in acute cerebellar slices obtained from adult (>2 months old) or juvenile (12-21 days old) rats and mice. Strikingly, and in contrast to juvenile DCN cells, cadmium did not affect the pacemaking of adult DCN cells. The activity of Purkinje cells (PCs) however was transformed into high-frequency bursting, regardless the age. Further, we questioned whether these findings could be due to an artifact associated with the added difficulty of preparing adult DCN slices. Hence we proceeded to examine the spontaneous activity of DCN neurons in anesthetized juvenile and adult rats and mice in vivo. When cadmium was injected into the DCN in vivo no significant change in firing rate was observed, conversely to most juvenile DCN neurons which showed high-frequency bursts after cadmium injection. In these same animals, PCs pacemaking showed no developmental difference. Thus our results demonstrate a remarkable age-dependent functional modification in the regulation of DCN neurons pacemaking. PMID- 26902516 TI - Activation of type 5 metabotropic glutamate receptor promotes the proliferation of rat retinal progenitor cell via activation of the PI-3-K and MAPK signaling pathways. AB - The metabotropic glutamate receptor 5 (mGluR5) regulates neurogenesis in the brain, but the effect of mGluR5 on retinal progenitor cells (RPCs) remains unknown. In this study, we found that mGluR5 promoted the proliferation of rat RPCs with activation of the phosphatidylinositol-3-kinase (PI-3-K) and mitogen activated protein kinase (MAPK) signaling pathways in vitro. The mGluR5 agonist (S)-3,5-dihydroxyphenylglycine hydrate (DHPG) increased the cellular viability in a concentration- and time-dependent manner, whereas the mGluR5 antagonist 6 methyl-2-(phenylethynyl)pyridine hydrochloride (MTEP) had the opposite effect, as shown by 3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine hydrochloride (MTT) assay. Treatment with DHPG (100 MUM) also promoted the proliferation of RPCs, as indicated by 5-Bromo-2-deoxyUridine (BrdU) staining and flow cytometry, and likewise, MTEP (100 MUM) and mGluR5 knockdown abolished the action of mGluR5 activity. Western blot demonstrated that the activation of mGluR5 enhanced the expression of Cyclin D1 and the phosphorylation level of PKC however, MTEP or mGluR5 knockdown also abrogated the effect of DHPG on RPCs. Furthermore, we found that activation of the extracellular signal-regulated protein kinase (ERK) and protein kinase B (AKT) signaling pathways was involved in the proliferation of RPC. After DHPG treatment, the levels of both p-ERK1/2 and p-AKT increased in a time-dependent manner. Then we used MTEP, mGluR5 knockdown, the ERK1/2 inhibitor U0126 and the AKT inhibitor LY294002 to pretreat the cells, and all of them clearly eliminated the influence of DHPG. These results demonstrated that mGluR5 regulates neurogenesis in RPCs through the MAPK and PI-3-K signaling pathways, and these findings may motivate a pharmacological study investigating a potential mechanism for the treatment of retinal diseases such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD). PMID- 26902518 TI - Precision Medicine, Cardiovascular Disease and Hunting Elephants. AB - Precision medicine postulates improved prediction, prevention, diagnosis and treatment of disease based on patient specific factors especially DNA sequence (i.e., gene) variants. Ideas related to precision medicine stem from the much anticipated "genetic revolution in medicine" arising seamlessly from the human genome project (HGP). In this essay I deconstruct the concept of precision medicine and raise questions about the validity of the paradigm in general and its application to cardiovascular disease. Thus far precision medicine has underperformed based on the vision promulgated by enthusiasts. While niche successes for precision medicine are likely, the promises of broad based transformation should be viewed with skepticism. Open discussion and debate related to precision medicine are urgently needed to avoid misapplication of resources, hype, iatrogenic interventions, and distraction from established approaches with ongoing utility. Failure to engage in such debate will lead to negative unintended consequences from a revolution that might never come. PMID- 26902517 TI - SGLT1 activity in lung alveolar cells of diabetic rats modulates airway surface liquid glucose concentration and bacterial proliferation. AB - High glucose concentration in the airway surface liquid (ASL) is an important feature of diabetes that predisposes to respiratory infections. We investigated the role of alveolar epithelial SGLT1 activity on ASL glucose concentration and bacterial proliferation. Non-diabetic and diabetic rats were intranasally treated with saline, isoproterenol (to increase SGLT1 activity) or phlorizin (to decrease SGLT1 activity); 2 hours later, glucose concentration and bacterial proliferation (methicillin-resistant Sthaphylococcus aureus, MRSA and Pseudomonas aeruginosa, P. aeruginosa) were analyzed in bronchoalveolar lavage (BAL); and alveolar SGLT1 was analyzed by immunohistochemistry. BAL glucose concentration and bacterial proliferation increased in diabetic animals: isoproterenol stimulated SGLT1 migration to luminal membrane, and reduced (50%) the BAL glucose concentration; whereas phlorizin increased the BAL glucose concentration (100%). These regulations were accompanied by parallel changes of in vitro MRSA and P. aeruginosa proliferation in BAL (r = 0.9651 and r = 0.9613, respectively, Pearson correlation). The same regulations were observed in in vivo P. aeruginosa proliferation. In summary, the results indicate a relationship among SGLT1 activity, ASL glucose concentration and pulmonary bacterial proliferation. Besides, the study highlights that, in situations of pulmonary infection risk, such as in diabetic subjects, increased SGLT1 activity may prevent bacterial proliferation whereas decreased SGLT1 activity can exacerbate it. PMID- 26902520 TI - Generation of Customizable Micro-wavy Pattern through Grayscale Direct Image Lithography. AB - With the increasing amount of research work in surface studies, a more effective method of producing patterned microstructures is highly desired due to the geometric limitations and complex fabricating process of current techniques. This paper presents an efficient and cost-effective method to generate customizable micro-wavy pattern using direct image lithography. This method utilizes a grayscale Gaussian distribution effect to model inaccuracies inherent in the polymerization process, which are normally regarded as trivial matters or errors. The measured surface profiles and the mathematical prediction show a good agreement, demonstrating the ability of this method to generate wavy patterns with precisely controlled features. An accurate pattern can be generated with customizable parameters (wavelength, amplitude, wave shape, pattern profile, and overall dimension). This mask-free photolithography approach provides a rapid fabrication method that is capable of generating complex and non-uniform 3D wavy patterns with the wavelength ranging from 12 MUm to 2100 MUm and an amplitude-to wavelength ratio as large as 300%. Microfluidic devices with pure wavy and wavy herringbone patterns suitable for capture of circulating tumor cells are made as a demonstrative application. A completely customized microfluidic device with wavy patterns can be created within a few hours without access to clean room or commercial photolithography equipment. PMID- 26902519 TI - The Use of Behavior Change Techniques and Theory in Technologies for Cardiovascular Disease Prevention and Treatment in Adults: A Comprehensive Review. AB - This review examined the use of health behavior change techniques and theory in technology-enabled interventions targeting risk factors and indicators for cardiovascular disease (CVD) prevention and treatment. Articles targeting physical activity, weight loss, smoking cessation and management of hypertension, lipids and blood glucose were sourced from PubMed (November 2010-2015) and coded for use of 1) technology, 2) health behavior change techniques (using the CALO-RE taxonomy), and 3) health behavior theories. Of the 984 articles reviewed, 304 were relevant (240=intervention, 64=review). Twenty-two different technologies were used (M=1.45, SD=+/-0.719). The most frequently used behavior change techniques were self-monitoring and feedback on performance (M=5.4, SD=+/-2.9). Half (52%) of the intervention studies named a theory/model - most frequently Social Cognitive Theory, the Trans-theoretical Model, and the Theory of Planned Behavior/Reasoned Action. To optimize technology-enabled interventions targeting CVD risk factors, integrated behavior change theories that incorporate a variety of evidence-based health behavior change techniques are needed. PMID- 26902521 TI - Physicochemical characterization of spray-dried PLGA/PEG microspheres, and preliminary assessment of biological response. AB - CONTEXT: The use of spray-drying to prepare blended PLGA:PEG microspheres with lower immune detection. OBJECTIVE: To study physical properties, polymer miscibility and alveolar macrophage response for blended PLGA:PEG microspheres prepared by a laboratory-scale spray-drying process. METHODS: Microspheres were prepared by spray-drying 0-20% w/w ratios of PLGA 65:35 and PEG 3350 in dichloromethane. Particle size and morphology was studied using scanning electron microscopy. Polymer miscibility and residual solvent levels evaluated by thermal analysis (differential scanning calorimetry - DSC and thermogravimetric analysis TGA). Immunogenicity was assessed in vitro by response of rat alveolar macrophages (NR8383) by the MTT-based cell viability assay and reactive oxygen species (ROS) detection. RESULTS: The spray dried particles were spherical, with a size range of about 2-3 um and a yield of 16-60%. Highest yield was obtained at 1% PEG concentration. Thermal analysis showed a melting peak at 59 degrees C (enthalpy: 170.61 J/g) and a degradation-onset of 180 degrees C for PEG 3350. PLGA 65:35 was amorphous, with a Tg of 43 degrees C. Blended PLGA:PEG microspheres showed a delayed degradation-onset of 280 degrees C, and PEG enthalpy-loss corresponding to 15% miscibility of PEG in PLGA. NR8383 viability studies and ROS detection upon exposure to these cells suggested that blended PLGA:PEG microspheres containing 1 and 5% PEG are optimal in controling cell proliferation and activation. CONCLUSION: This research establishes the feasibility of using a spray-drying process to prepare spherical particles (2-3 um) of molecularly-blended PLGA 65:35 and PEG 3350. A PEG concentration of 1-5% was optimal to maximize process yield, with minimal potential for immune detection. PMID- 26902522 TI - Sex differences in the association between obesity and albuminuria among Korean adults: a cross-sectional study using the Korea National Health and Nutrition Examination Survey data. AB - BACKGROUND: The association between obesity and albuminuria in the general population remains unclear. We aimed to identify the association between obesity and albuminuria as well as sex differences regarding the associations using several obesity indices, including waist circumference (WC), body mass index (BMI), and waist-to-height ratio (WHR). METHODS: This study included 3841 subjects (1730 males and 2111 females; age 20-80 years) who participated in the Fifth Korea National Health and Nutrition Examination Survey conducted in 2011. Subjects with hypertension, diabetes, renal failure, or a malignant tumor and those who were pregnant or menstruating were excluded. Albuminuria was defined as a urinary albumin-to-creatinine ratio >=30 mg/g. Anthropometric parameters were categorized into sex-specific quartiles. Logistic regression models were used to assess the associations between each anthropometric parameter and albuminuria. RESULTS: All of the obesity indices of the fourth quartile group of females showed a twofold higher risk for albuminuria than the second quartile group, and it was persistently significant after adjusting for age, smoking, and physical activity. After further adjustment for high blood pressure and impaired fasting glucose and triglyceride levels, WC and BMI of the fourth quartile group of females still showed a significantly higher risk for albuminuria than the second quartile group (odds ratios 1.96 and 2.24; 95 % confidence intervals 1.03-3.74 and 1.15-4.37). None of the associations between albuminuria and the obesity indices were significant in males. CONCLUSION: Higher WC and BMI were significantly associated with the risk of albuminuria among females, but not males. PMID- 26902524 TI - Pore-Scale Modeling of Non-Newtonian Shear-Thinning Fluids in Blood Oxygenator Design. AB - This paper reviews and further develops pore-scale computational flow modeling techniques used for creeping flow through orthotropic fiber bundles used in blood oxygenators. Porous model significantly reduces geometrical complexity by taking a homogenization approach to model the fiber bundles. This significantly simplifies meshing and can avoid large time-consuming simulations. Analytical relationships between permeability and porosity exist for Newtonian flow through regular arrangements of fibers and are commonly used in macroscale porous models by introducing a Darcy viscous term in the flow momentum equations. To this extent, verification of analytical Newtonian permeability-porosity relationships has been conducted for parallel and transverse flow through square and staggered arrangements of fibers. Similar procedures are then used to determine the permeability-porosity relationship for non-Newtonian blood. The results demonstrate that modeling non-Newtonian shear-thinning fluids in porous media can be performed via a generalized Darcy equation with a porous medium viscosity decomposed into a constant term and a directional expression through least squares fitting. This concept is then investigated for various non-Newtonian blood viscosity models. The proposed methodology is conducted with two different porous model approaches, homogeneous and heterogeneous, and validated against a high-fidelity model. The results of the heterogeneous porous model approach yield improved pressure and velocity distribution which highlights the importance of wall effects. PMID- 26902523 TI - 4D-Listmode-PET-CT and 4D-CT for optimizing PTV margins in gastric lymphoma : Determination of intra- and interfractional gastric motion. AB - PURPOSE: New imaging protocols for radiotherapy in localized gastric lymphoma were evaluated to optimize planning target volume (PTV) margin and determine intra-/interfractional variation of the stomach. METHODS: Imaging of 6 patients was explored prospectively. Intensity-modulated radiotherapy (IMRT) planning was based on 4D/3D imaging of computed tomography (CT) and positron-emission tomography (PET)-CT. Static and motion gross tumor volume (sGTV and mGTV, respectively) were distinguished by defining GTV (empty stomach), clinical target volume (CTV = GTV + 5 mm margin), PTV (GTV + 10/15/20/25 mm margins) plus paraaortic lymph nodes and proximal duodenum. Overlap of 4D-Listmode-PET-based mCTV with 3D-CT-based PTV (increasing margins) and V95/D95 of mCTV were evaluated. Gastric shifts were determined using online cone-beam CT. Dose contribution to organs at risk was assessed. RESULTS: The 4D data demonstrate considerable intra-/interfractional variation of the stomach, especially along the vertical axis. Conventional 3D-CT planning utilizing advancing PTV margins of 10/15/20/25 mm resulted in rising dose coverage of mCTV (4D-Listmode-PET Summation-CT) and rising D95 and V95 of mCTV. A PTV margin of 15 mm was adequate in 3 of 6 patients, a PTV margin of 20 mm was adequate in 4 of 6 patients, and a PTV margin of 25 mm was adequate in 5 of 6 patients. CONCLUSION: IMRT planning based on 4D-PET-CT/4D-CT together with online cone-beam CT is advisable to individualize the PTV margin and optimize target coverage in gastric lymphoma. PMID- 26902525 TI - Assistive peripheral phosphene arrays deliver advantages in obstacle avoidance in simulated end-stage retinitis pigmentosa: a virtual-reality study. AB - OBJECTIVE: The prospective efficacy of peripheral retinal prostheses for guiding orientation and mobility in the absence of residual vision, as compared to an implant for the central visual field (VF), was evaluated using simulated prosthetic vision (SPV). APPROACH: Sighted volunteers wearing a head-mounted display performed an obstacle circumvention task under SPV. Mobility and orientation performance with three layouts of prosthetic vision were compared: peripheral prosthetic vision of higher visual acuity (VA) but limited VF, of wider VF but limited VA, as well as centrally restricted prosthetic vision. Learning curves using these layouts were compared fitting an exponential model to the mobility and orientation measures. MAIN RESULTS: Using peripheral layouts, performance was superior to the central layout. Walking speed with both higher acuity and wider-angle layouts was 5.6% higher, and mobility errors reduced by 46.4% and 48.6%, respectively, as compared to the central layout. The wider-angle layout yielded the least number of collisions, 63% less than the higher-acuity and 73% less than the central layout. Using peripheral layouts, the number of visual-scanning related head movements was 54.3% (higher-acuity) and 60.7% (wider angle) lower, as compared to the central layout, and the ratio of time standing versus time walking was 51.9% and 61.5% lower, respectively. Learning curves did not differ between layouts, except for time standing versus time walking, where both peripheral layouts achieved significantly lower asymptotic values compared to the central layout. SIGNIFICANCE: Beyond complementing residual vision for an improved performance, peripheral prosthetic vision can effectively guide mobility in the later stages of retinitis pigmentosa (RP) without residual vision. Further, the temporal dynamics of learning peripheral and central prosthetic vision are similar. Therefore, development of a peripheral retinal prosthesis and early implantation to alleviate VF constriction in RP should be considered to extend the target group and the time of benefit for potential retinal prosthesis implantees. PMID- 26902526 TI - Adherence to the 2013 Blood Cholesterol Guidelines in Patients With Diabetes at a PCMH: Comparison of Physician Only and Combination Physician/Pharmacist Visits. AB - PURPOSE: The purpose of this study is to assess adherence to the 2013 blood cholesterol guideline in a population with diabetes based on the atherosclerotic cardiovascular (ASCVD) risk. METHODS: Patients with diabetes were assessed to see whether they received the appropriate intensity statin therapy via chart review. Patients seen by a physician or pharmacist at CommUnityCare, a PCMH, from December 2013 to October 2014 were included in this retrospective study. The ASCVD risks were calculated to determine if the patients received appropriate intensity statin. RESULTS: A total of 583 patients met the inclusion criteria; there were 475 in the physician only group and 108 with additional pharmacist visits. Statin therapy was prescribed in 71% of patients in the physician group and 88% of patients in the pharmacist/physician group. The appropriate intensity statin was prescribed in 32% of patients in the physician group and 35% of patients in the pharmacist/physician group. The appropriate intensity statin in statin naive patients was prescribed in 45% of the physician group and 50% of patients in the pharmacist/physician group. CONCLUSION: The proportion of patients prescribed an appropriate intensity statin did not differ between patients managed by physicians alone compared to those managed by pharmacists and physicians. Overall adherence to the 2013 blood cholesterol guidelines was 33%, and this measure can be used as a baseline assessment of current adherence with the guidelines. PMID- 26902527 TI - Psychometric Evaluation of a Korean Version of the Adherence to Refills and Medications Scale (ARMS) in Adults With Type 2 Diabetes. AB - PURPOSE: The purpose of the study was to examine the reliability and validity of the Adherence to Refills and Medications Scale-Korean (ARMS-K) among Korean adults with type 2 diabetes. METHODS: The Korean translated ARMS-K was back translated to ensure translation equivalency. A cross-sectional survey was used to evaluate the psychometric properties with exploratory factor analysis for validity and Cronbach's alpha coefficients for reliability. RESULTS: The factor analysis of construct validity identified 3 dimensions of the ARMS-K, explaining 54.7% of the total variance. The internal consistency reliability for the total instrument was acceptable with a Cronbach's alpha of .801. There was good correlation between the ARMS-K and 8-item Morisky Medication Adherence Scale Korean version (r = -0.698), indicating that these scales measure theoretically related constructs as evidence of convergent validity. As evidence of known groups validity, there was a significant association between the ARMS-K score and glycemic control (P = .048), indicating that the good glycemic controlled group was more likely to have a higher rate of adherence to refills and medications than the poor glycemic controlled group. CONCLUSIONS: These results support the cross-cultural applicability of the concepts underlying the ARMS-K. The ARMS-K can be used not only to assess adherence to refills and medications in Koreans with diabetes but also to examine the potential role of adherence to refills and medications in enhanced glycemic control of people with diabetes in a variety of clinical settings. PMID- 26902529 TI - An Elderly Patient With Palpitation and a Negative Nuclear Stress Test Result. PMID- 26902528 TI - Association of Prenatal Diagnosis of Critical Congenital Heart Disease With Postnatal Brain Development and the Risk of Brain Injury. AB - IMPORTANCE: The relationship of prenatal diagnosis of critical congenital heart disease (CHD) with brain injury and brain development is unknown. Given limited improvement of CHD outcomes with prenatal diagnosis, the effect of prenatal diagnosis on brain health may reveal additional benefits. OBJECTIVE: To compare the prevalence of preoperative and postoperative brain injury and the trajectory of brain development in neonates with prenatal vs postnatal diagnosis of CHD. DESIGN, SETTING, AND PARTICIPANTS: Cohort study of term newborns with critical CHD recruited consecutively from 2001 to 2013 at the University of California, San Francisco and the University of British Columbia. Term newborns with critical CHD were studied with brain magnetic resonance imaging preoperatively and postoperatively to determine brain injury severity and microstructural brain development with diffusion tensor imaging by measuring fractional anisotropy and the apparent diffusion coefficient. Comparisons of magnetic resonance imaging findings and clinical variables were made between prenatal and postnatal diagnosis of critical CHD. A total of 153 patients with transposition of the great arteries and single ventricle physiology were included in this analysis. MAIN OUTCOMES AND MEASURES: The presence of brain injury on the preoperative brain magnetic resonance imaging and the trajectory of postnatal brain microstructural development. RESULTS: Among 153 patients (67% male), 96 had transposition of the great arteries and 57 had single ventricle physiology. The presence of brain injury was significantly higher in patients with postnatal diagnosis of critical CHD (41 of 86 [48%]) than in those with prenatal diagnosis (16 of 67 [24%]) (P = .003). Patients with prenatal diagnosis demonstrated faster brain development in white matter fractional anisotropy (rate of increase, 2.2%; 95% CI, 0.1%-4.2%; P = .04) and gray matter apparent diffusion coefficient (rate of decrease, 0.6%; 95% CI, 0.1%-1.2%; P = .02). Patients with prenatal diagnosis had lower birth weight (mean, 3184.5 g; 95% CI, 3050.3-3318.6) than those with postnatal diagnosis (mean, 3397.6 g; 95% CI, 3277.6-3517.6) (P = .02). Those with prenatal diagnosis had an earlier estimated gestational age at delivery (mean, 38.6 weeks; 95% CI, 38.2-38.9) than those with postnatal diagnosis (mean, 39.1 weeks; 95% CI, 38.8-39.5) (P = .03). CONCLUSIONS AND RELEVANCE: Newborns with prenatal diagnosis of single ventricle physiology and transposition of the great arteries demonstrate less preoperative brain injury and more robust microstructural brain development than those with postnatal diagnosis. These results are likely secondary to improved cardiovascular stability. The impact of these findings on neurodevelopmental outcomes warrants further study. PMID- 26902530 TI - Comparison of Triggering and Nontriggering Factors in ST-Segment Elevation Myocardial Infarction and Extent of Coronary Arterial Narrowing. AB - Various physical, emotional, and extrinsic triggers have been attributed to acute coronary syndrome. Whether a correlation can be drawn between identifiable ischemic triggers and the nature of coronary artery disease (CAD) still remains unclear. In the present study, we evaluated the correlation between triggered versus nontriggered ischemic symptoms and the extent of CAD in patients with ST segment elevation myocardial infarction (STEMI). We conducted a retrospective, single-center observational study including 1,345 consecutive patients with STEMI, treated with primary percutaneous coronary intervention. Acute physical and emotional triggers were identified in patients' historical data. Independent predictors of multivessel CAD were determined using a logistic regression model. A potential trigger was identified in 37% of patients. Physical exertion was found to be the most dominant trigger (65%) followed by psychological stress (16%) and acute illness (12%). Patients with nontriggered STEMI tended to be older and more likely to have co-morbidities. Patients with nontriggered STEMI showed a higher rate of multivessel CAD (73% vs 30%, p <0.001). In a multivariate regression model, nontriggered symptoms emerged as an independent predictor of multivessel CAD (odds ratio 8.33, 95% CI 5.74 to 12.5, p = 0.001). No specific trigger was found to predict independently the extent of CAD. In conclusion, symptoms onset without a recognizable trigger is associated with multivessel CAD in STEMI. Further studies will be required to elucidate the putative mechanisms underlying ischemic triggering. PMID- 26902531 TI - Higher bone mass in prepubertal and peripubertal female footballers. AB - OBJECTIVES: The main aim of this study was to compare the bone mass of female football players with controls of different pubertal stages. METHODS: Sixty five girls aged 8-14 years (10.14 +/- 0.1, Tanner stages I-IV) participated in the study. Twenty participants were prepubertal (10 prepubertal control) and 45 peripubertal (15 peripubertal control). All footballers trained two days per week while the control group did not perform regular physical activity outside of school. Body composition was assessed by Dual-energy X-ray absorptiometry. Analysis of covariance was performed to evaluate differences in lean and bone masses. RESULTS: Significant differences in lower-body extremities lean mass (LLM) between peripubertal groups were found (P < .05). Additionally, prepubertal footballers showed higher values of bone mineral content (BMC) at the femoral neck (P < .05) while peripubertal footballers exhibited enhanced BMC at the whole body, trochanter and Wards triangle area. Bone mineral density (BMD) was higher in footballers compared to their non-active peers at the femoral neck and intertrochanter (P < .05, respectively) while in the peripubertal footballers higher BMD values were found in almost all of the studied body sites. CONCLUSION: Female footballers showed higher bone and lean masses compared to control counterparts; these differences are already detectable at prepubertal ages and more consistent after pubertal spurt. PMID- 26902532 TI - Higher dietary diversity is related to better visual and auditory sustained attention. AB - Attention is a complex cognitive function that is necessary for learning, for following social norms of behaviour and for effective performance of responsibilities and duties. It is especially important in sensitive occupations requiring sustained attention. Improvement of dietary diversity (DD) is recognised as an important factor in health promotion, but its association with sustained attention is unknown. The aim of this study was to determine the association between auditory and visual sustained attention and DD. A cross sectional study was carried out on 400 women aged 20-50 years who attended sports clubs at Tehran Municipality. Sustained attention was evaluated on the basis of the Integrated Visual and Auditory Continuous Performance Test using Integrated Visual and Auditory software. A single 24-h dietary recall questionnaire was used for DD assessment. Dietary diversity scores (DDS) were determined using the FAO guidelines. The mean visual and auditory sustained attention scores were 40.2 (sd 35.2) and 42.5 (sd 38), respectively. The mean DDS was 4.7 (sd 1.5). After adjusting for age, education years, physical activity, energy intake and BMI, mean visual and auditory sustained attention showed a significant increase as the quartiles of DDS increased (P=0.001). In addition, the mean subscales of attention, including auditory consistency and vigilance, visual persistence, visual and auditory focus, speed, comprehension and full attention, increased significantly with increasing DDS (P<0.05). In conclusion, higher DDS is associated with better visual and auditory sustained attention. PMID- 26902533 TI - The effect of laparoscopic sleeve gastrectomy (LSG) on glycemic control in morbidly obese patients. AB - INTRODUCTION: Bariatric procedures have become popular in treating not only the morbid obesity but also the metabolic derangements. Sleeve Gastrectomy has recently become popular as a standalone procedure and its usefulness as a metabolic procedure especially glycemic control is still under investigation. One of the most commonly used measure of insulin resistance is statistically derived 'Homeostatic model assessment of insulin resistance (HOMA-IR). AIM: The effect of Laparoscopic Sleeve Gastrectomy (LSG) on clinical and measurable change in glycemic control as seen by reduction of insulin resistance ie HOMA-IR levels in morbidly obese patients. MATERIAL AND METHODS: All the patients with BMI >=35 kg/m(2) with co morbidities and BMI >=40 kg/m(2) even without co morbidities were included in the study. The period of the study was from Feb 2013 to Sep 2014. Fasting (FBS), post prandial blood sugar (PPBS) and Insulin levels were checked before the surgery, 1month and 3 month after the surgery. We also recorded BMI and diabetic status. HOMA-IR was calculated and trends were recorded. STATISTICAL ANALYSIS: Statistical analysis was carried out using SPSS 16.0. RESULTS: Out of 28 patients 8 were males and 20 were females. The mean age was 43 yrs. 11 (39%) patients were diabetic and mean BMI was 44 kg/m(2) and a range of (35-61.3) kg/m(2). 11 patients had BMI > 45 kg/m(2). The HOMA-IR values decreased significantly after the surgery both in diabetics and non diabetics. CONCLUSION: LSG results in improvement in glycemic control in both diabetics and non diabetics. PMID- 26902535 TI - Diastereodivergent Access to Syn and Anti 3,4-Substituted beta Fluoropyrrolidines: Enhancing or Reversing Substrate Preference. AB - A practical diastereodivergent access to beta-fluoropyrrolidines with two adjacent stereocenters has been demonstrated, by either enhancing or completely reversing the substrate control, in the diastereoselective fluorination of a series of diverse pyrrolidinyl carbaldehydes using organocatalysis. Furthermore, enamine catalysis has been successfully utilized for kinetic resolution, obtaining a fluorinated beta-prolinol analogue with two adjacent tetrasubstituted chiral centers in 95% ee from a racemic substrate. PMID- 26902534 TI - Positive surgical margins in surgically treated unifocal and multifocal IPMN. AB - INTRODUCTION: Although treatment methods for the positive margins of surgically treated intraductal papillary mucinous neoplasms (IPMNs) are established, the significance of the positive surgical margins remains unclear. We aimed to clarify the risk factors of the positive margins and their impact on the recurrence of cystic lesions. METHODS: Fifty-five surgically treated IPMN cases occurring at the Ogaki Municipal Hospital from 2004 to 2013 were analyzed retrospectively. RESULTS: Out of the 55 IPMN patients who underwent pancreatectomy, positive surgical margins were found in 16 cases. Most of the positive surgical margin cases were found to be a multifocal IPMN; specifically, 9 out of 19 were a multifocal IPMN case, and 7 out of 36 were a unifocal IPMN case (47.4% and 19.4%, respectively, p = 0.030). Recurrences of cystic lesions in the remnant pancreases were found in 7 cases; 4 out of 16 cases were in the positive margin group, and 3 out of 39 were in the negative margin group (25.0% and 7.7%, respectively, p = 0.080). While a positive margin was a significant risk factor in unifocal IPMN (p = 0.031), it was not in multifocal IPMN (p = 0.90). CONCLUSION: Positive surgical margins are frequently found in multifocal IPMNs and might include false positive margins. PMID- 26902536 TI - High-resolution Identification and Separation of Living Cell Types by Multiple microRNA-responsive Synthetic mRNAs. AB - The precise identification and separation of living cell types is critical to both study cell function and prepare cells for medical applications. However, intracellular information to distinguish live cells remains largely inaccessible. Here, we develop a method for high-resolution identification and separation of cell types by quantifying multiple microRNA (miRNA) activities in live cell populations. We found that a set of miRNA-responsive, in vitro synthesized mRNAs identify a specific cell population as a sharp peak and clearly separate different cell types based on less than two-fold differences in miRNA activities. Increasing the number of miRNA-responsive mRNAs enhanced the capability for cell identification and separation, as we precisely and simultaneously distinguished different cell types with similar miRNA profiles. In addition, the set of synthetic mRNAs separated HeLa cells into subgroups, uncovering heterogeneity of the cells and the level of resolution achievable. Our method could identify target live cells and improve the efficiency of cell purification from heterogeneous populations. PMID- 26902537 TI - An organic indicator functionalized graphene oxide nanocomposite-based colorimetric assay for the detection of sarcosine. AB - Rapid detection of sarcosine is a key requirement for both diagnosis and treatment of disease. We report here a simple yet sensitive colorimetric nanocomposite platform for rapid detection of sarcosine in alkaline media. The approach exploited the benefits of a rapid color-producing reaction between an organic indicator, 1,2-naphthoquinone-4-sulphonic acid sodium salt (NQS), and the analyte of sarcosine species as well as the good catalytic ability of graphene oxide (GO) to the formation of highly colored products due to its good water dispersibility, extremely large surface area and facile surface modification. As a result, a NQS functionalized GO nanocomposite through pi-pi stacking has been demonstrated to be useful as a highly efficient catalyst system for the selective and sensitive colorimetric determination of sarcosine by providing a nanocomposite-amplified colorimetric response. Meanwhile, the strategy offered excellent selectivity toward sarcosine species against other amino acids as well as a satisfying detection limit of 0.73 MUM. More importantly, by using an electrochemical method, a credible sensing mechanism of GO nanocomposite-based colorimetric platform for a special analyte determination can be easily verified and elucidated, which also provides an attractive alternative to conventional characterization strategies. PMID- 26902538 TI - Role of the C1858T polymorphism of protein tyrosine phosphatase non-receptor type 22 (PTPN22) in children and adolescents with type 1 diabetes. AB - In recent years, increasing interest has been devoted to the susceptibility gene polymorphisms in type 1 diabetes (T1D) as well as in other autoimmune diseases. Among these, a nucleotide polymorphism of the gene encoding for the protein tyrosine phosphatase non-receptor type 22 (PTPN22) has been associated with T1D in several studies. The aim of this study is to define the frequency of the C1858T polymorphism in the PTPN22 gene in a cohort of 113 Caucasian patients (58 males and 55 females) with T1D, and to assess a possible correlation with a group of clinically relevant variables: age at onset, gender, diabetes-related autoantibodies, residual beta-cell function and daily insulin requirement (IR) 6 months after diagnosis. Using a PCR-RFLP approach, we evidenced a 17.7% frequency of the PTPN22 C1858T polymorphism in diabetic patients, higher than the frequency showed in the general population. A statistically significant correlation between this polymorphism and higher levels of C-peptide at diagnosis and lower IR at 6 months from diagnosis was observed (P=0.001 and P=0.04). Moreover, 1858T variant carriers were more frequently positive for glutamic acid decarboxylase (GAD) autoantibodies at diagnosis than wild-type subjects (P=0.19). On the other hand, no significant difference regarding age at onset, gender distribution, insulinoma associated 2 molecule (IA2) and islet cell antibodies (ICA) positivity was found. These findings, if adequately confirmed in the future and extended to larger samples, may characterize a subset of T1D patients with a defined genetic pattern, who may be eligible for trials aimed to preserve residual beta-cell function in the coming years. PMID- 26902539 TI - The effect of genetic variation in PCSK9 on the LDL-cholesterol response to statin therapy. AB - Statins (HMG-CoA reductase inhibitors) lower low-density lipoprotein cholesterol (LDL-C) and prevent cardiovascular disease. However, there is wide individual variation in LDL-C response. Drugs targeting proprotein convertase subtilin/kexin type 9 (PCSK9) lower LDL-C and will be used with statins. PCSK9 mediates the degradation of LDL receptors (LDLRs). Therefore, a greater LDL-C response to statins would be expected in individuals with PCSK9 loss-of-function (LOF) variants because LDLR degradation is reduced. To examine this hypothesis, the effect of 11 PCSK9 functional variants on statin response was determined in 669 African Americans. One LOF variant, rs11591147 (p.R46L) was significantly associated with LDL-C response to statin (P=0.002). In the three carriers, there was a 55.6% greater LDL-C reduction compared with non-carriers. Another functional variant, rs28362261 (p.N425S), was marginally associated with statin response (P=0.0064).The effect of rs11591147 was present in individuals of European ancestry (N=2388, P=0.054). The therapeutic effect of statins may be modified by genetic variation in PCSK9. PMID- 26902540 TI - Health regulatory communications of well-established safety-related pharmacogenomics associations in six developed countries: an evaluation of alignment. AB - Recommendations on genetic testing are typically conveyed by drug regulatory authorities through drug labels, which are legal requirements for market authorization of drugs. We conducted a cross-sectional study of drug labels focusing on three crucial aspects of regulatory pharmacogenomics communications: (i) intent; (ii) interpretation in the local context; and (iii) implications of the genetic information. Labels of drugs associated with well-established safety related genetic markers for adverse drug reactions across six developed countries of United States, Canada, United Kingdom, Australia, New Zealand and Singapore were reviewed. We found differing medical advice for genotype-positive HLA B*15:02, HLA-A*31:01, UGT1A1*28 and CYP2D6 ultra-rapid metabolisers in breastfeeding women. This raises questions on implications to clinical practice between these countries. Varying ways of presenting at-risk population and allele frequencies also raises question in incorporating such information in drug labels. An international guidance addressing these crucial aspects of regulatory pharmacogenomic communications in drug labels is long overdue. PMID- 26902541 TI - Validation of a Spanish version of the Leicester Cough Questionnaire in non cystic fibrosis bronchiectasis. AB - The Leicester Cough Questionnaire (LCQ) has been validated in non-cystic fibrosis bronchiectasis (NCFBC). The present study aimed to create and validate a Spanish version of the LCQ (LCQ-Sp) in NCFBC. The LCQ-Sp was developed following a standardized protocol. For reliability, we assessed internal consistency and the change in score over a 15-day period in stable state. For responsiveness, we assessed the change in scores between visit 1 and the first exacerbation. For validity, we evaluated convergent validity through correlation with the Saint George's Respiratory Questionnaire (SGRQ) and discriminant validity. Two hundred fifty-nine patients (118 mild bronchiectasis, 90 moderate bronchiectasis and 47 severe bronchiectasis) were included. Internal consistency was high for the total scoring and good for the different domains (Cronbach's alpha: 0.86-0.91). The test-retest reliability shows an intraclass correlation coefficient of 0.87 for the total score. The mean LCQ-Sp score at visit 1 decreased at the beginning of an exacerbation (15.13 +/- 4.06 vs. 12.24 +/- 4.64; p < 0.001). The correlation between LCQ-Sp and SGRQ scores was -0.66 (p < 0.01). The differences in the LCQ Sp total score between the different groups of severity were significant (p < 0.001). The LCQ-Sp discriminates disease severity, is responsive to change when faced with exacerbations and is reliable for use in bronchiectasis. PMID- 26902543 TI - Design and cognitive evaluation of 6 dynamic lane departure warning symbols. AB - OBJECTIVE: Lane departure, caused by inattention, distraction, drowsiness, or any unusual driver behavior, is a typical risk threatening the driver as well as other road users. Accurate perception of such situations through effective warnings would help drivers to avoid serious consequences. With regard to critical functions of warning symbols for risk communication, the present study focused on providing effective and easily perceivable symbols, compatible with human cognitive capabilities. Thus, the main purpose of the present study was to design and cognitively appraise 6 newly designed dynamic symbols, candidates for a new type of lane departure warning system. METHODS: Simplicity, familiarity, concreteness, meaningfulness, and semantic closeness were the major assessment criteria, defining cognitive features by the earlier researchers in the field. A total number of 187 driving license applicants, with a mean age of 20.58 years (SD = 3.20), participated in the present survey. The participants rated cognitive features of the 6 dynamic symbols along a 0-100 scale. RESULTS: Significant main effect of the element factor type of the designed symbols on rating cognitive features revealed that the existence of car element was the best predictor for illustrating lane departure. The interaction of both element factor and location of element factor significantly affected the ratings. However, the location of element factor did not solely have any strong effect on the ratings. The results also demonstrated that semantic closeness received the highest overall mean score across symbols (M = 61.80), especially within the symbols that include the car element (M = 75.67). Moreover, a significant difference was observed between the average ratings of the cognitive features, despite the fact that a significant correlation was found between cognitive features. CONCLUSION: The most considerable result of the current study was the match between the symbol with the highest ratings and the International Organization for Standardization (ISO) related icon in appearance. Because previous studies demonstrated a strong correlation between comprehension scores of the symbol and both semantic closeness and meaningfulness, high-level comprehensibility of the best ranked symbol is expected. PMID- 26902542 TI - Rural and remote care: Overcoming the challenges of distance. AB - The challenges of providing quality respiratory care to persons living in rural or remote communities can be daunting. These populations are often vulnerable in terms of both health status and access to care, highlighting the need for innovation in service delivery. The rapidly expanding options available using telehealthcare technologies have the capacity to allow patients in rural and remote communities to connect with providers at distant sites and to facilitate the provision of diagnostic, monitoring, and therapeutic services. Successful implementation of telehealthcare programs in rural and remote settings is, however, contingent upon accounting for key technical, organizational, social, and legal considerations at the individual, community, and system levels. This review article discusses five types of telehealthcare delivery that can facilitate respiratory care for residents of rural or remote communities: remote monitoring (including wearable and ambient systems; remote consultations (between providers and between patients and providers), remote pulmonary rehabilitation, telepharmacy, and remote sleep monitoring. Current and future challenges related to telehealthcare are discussed. PMID- 26902545 TI - Use of rapid needs assessment as a tool to identify vaccination delays in Guatemala and Peru. AB - OBJECTIVE: To explore the use of rapid needs assessment (RNA) surveys to determine the prevalence and factors contributing to delays in vaccination of children in two low middle-income countries (LMIC). METHODS: Data from two RNA surveys performed as part of program improvement evaluations in Guatemala and Peru were used for this analysis. The primary endpoint was the timeliness of immunization with delay defined as administration of vaccines beyond 28 days from recommended age for DTwP-HepB-Hib (Penta) and measles-mumps-rubella (MMR) vaccines, as well as past age-restrictions for rotavirus vaccine. Independent risk factors analyzed included child's gender, birth year, number of children in household, maternal age, maternal education, and food insecurity. RESULTS: Vaccine information was available from 811 children from 838 households surveyed. High rate of immunization delays was observed, with 75.6% of children in Guatemala and 57.8% of children in Peru being delayed for the third dose of Penta primary series. Factors associated with delayed vaccination in Guatemala included advanced maternal age and increased number of children in household. In Peru, significant associations were birth year before 2009, lower maternal education level, and increased number of children in household. CONCLUSIONS: RNA is a fast and effective method to identify timely vaccine coverage and derive a hypothesis of factors possibly associated with vaccination delay. PMID- 26902544 TI - Blood biochemical changes in mice after administration of a mixture of three anesthetic agents. AB - Currently, from the viewpoint of animal welfare, anesthesia or analgesia is required during experimental procedures in animals that are likely to cause pain. A part of these anesthetics have been reported to influence a blood biochemical level. It is important for us to understand the effect of the anesthetic on blood biochemistry when we choose the anesthetic agent to be used in experiments. In this study, we examined the blood biochemical changes in mice after administration of a new mixture of three anesthetic agents -medetomidine / midazolam / butorphanol (MMB). We subcutaneously administered two dose combinations of MMB (0.45 / 6 / 7.5 and 0.9 / 12 / 15 mg/kg) in mice, followed by administration of atipamezole, for reversal of anesthetic effects, after 1 hr. Thereafter, blood biochemistry was assessed at 1, 4 and 24 hr after MMB administration. We observed that MMB administration caused a transient increase in blood sugar, inorganic phosphorus, potassium and creatine kinase levels. These, however, returned to the reference range 24 hr after MMB administration. In conclusion, MMB changes the levels of some blood biochemical parameters, but not to an extent that would threaten health. However, when using laboratory animals, this effect of MMB may influence the experimental results, depending on the experimental content. Hence, the choice of anesthetic agents used in laboratory animals should be based on detailed knowledge of their pharmacological effects. PMID- 26902546 TI - Effect of change in sequence of administration of DTwP and Hepatitis B vaccines on perception of pain in infants: A randomized control trial. AB - OBJECTIVE: This study was designed with objective to study pain response of infants to change in sequence of administration of Hepatitis B and DTwP vaccines. METHODS: This was a randomized parallel control trial. The study was carried out in the immunization clinic of the Department of Pediatrics, LLRM Medical College, Meerut. One hundred and thirty healthy term infants up to 4 months of age were injected either DTwP vaccine first or Hepatitis B vaccine first, followed one minute later by the other vaccine. RESULT: Baseline characteristics did not differ between the groups. The mean (SD) of AUC of MFCS and NIPS was significantly more in DF group as compared to HF group (for MFCS 25.5 +/- 5.4 versus 22.5 +/- 5.5, p<0.01; for NIPS 31.77 +/- 5.5 versus 27.64 +/- 6.9, p < 0.01). Similarly mean (SD) of AUC of Heart rate and saturation of oxygen showed significant variation in DF group as compared to HF group (for heart rate 591.6 +/- 55 versus 559.6 +/- 49, p< 0.01; for SpO2 326.4 +/- 12 versus 335 +/- 8, p < 0.01). CONCLUSION: These results showed that infant experienced lesser pain when Hepatitis B was administered first than when DTwP vaccine was given first. PMID- 26902547 TI - Venom conjugated polylactide applied as biocompatible material for passive and active immunotherapy against scorpion envenomation. AB - Scorpion envenoming represents a public health issue in subtropical regions of the world. Treatment and prevention need to promote antitoxin immunity. Preserving antigenic presentation while removing toxin effect remains a major challenge in toxin vaccine development. Among particulate adjuvant, particles prepared with poly (D,L-lactide) polymer are the most extensively investigated due to their excellent biocompatibility and biodegradability. The aim of this study is to develop surfactant-free PLA nanoparticles that safely deliver venom toxic fraction to enhance specific immune response. PLA nanoparticles are coated with AahG50 (AahG50/PLA) and BotG50 (BotG50/PLA): a toxic fraction purified from Androctonus australis hector and Buthus occitanus tunetanus venoms, respectively. Residual toxicities are evaluated following injections of PLA-containing high doses of AahG50 (or BotG50). Immunization trials are performed with the detoxified fraction administered alone without adjuvant. A comparative study of the effect of Freund is also included. The neutralizing capacity of sera is determined in naive mice. Six months later, immunized mice are challenged subcutaneously with increased doses of AahG50. Subcutaneous lethal dose 50 (LD50) of AahG50 and BotG50 is of 575 MUg/kg and 1300 MUg/kg respectively. By comparison, BotG50/PLA is totally innocuous while 50% of tested mice survive 2875 MUg AahG50/kg. Alhydrogel and Freund are not able to detoxify such a high dose. Cross-antigenicity between particulate and soluble fraction is also, ensured. AahG50/PLA and BotG50/PLA induce high antibody levels in mice serum. The neutralizing capacity per mL of anti-venom was 258 MUg/mL and 186 MUg/mL calculated for anti-AahG50/PLA and anti-BotG50/PLA sera, respectively. Animals immunized with AahG50/PLA are protected against AahG50 injected dose of 3162 MUg/kg as opposed all non-immunized mice died at this dose. We find that the detoxification approach based PLA nanoparticles, benefit the immunogenicity and protective efficacy of venom immunogen. PMID- 26902549 TI - Shock Index as a Predictor of Myocardial Damage and Clinical Outcome in ST Elevation Myocardial Infarction. AB - BACKGROUND: Data on the prognostic value of the shock index in patients with ST elevation myocardial infarction (STEMI) are scarce. Furthermore, the relationship of the shock index with myocardial damage is unknown. The aim of this study was to evaluate the association of the shock index with markers of myocardial damage and clinical outcome in patients with STEMI. METHODS AND RESULTS: This multicenter study analyzed 791 patients. Patients were categorized in 2 groups according to the admission shock index (optimized cut-off=0.62). Infarct severity was determined by cardiac magnetic resonance (CMR) imaging. Patients with cardiogenic shock that were unable to undergo CMR acquisition were excluded. Major adverse cardiac events (MACE) were defined as a composite of death, reinfarction and congestive heart failure within 12 months. Patients with elevated admission shock index (n=321 [40.6%]) had a significantly larger area-at risk (37.6 [27.8-50.4] % of left ventricular volume [LV] vs. 34.3 [24.5-46.0] % LV, P=0.02), larger infarct size (19.5 [10.7-28.0] % LV vs. 14.9 [7.7-22.3] % LV, P<0.001), lower myocardial salvage index (46.2 [27.9-64.5] vs. 53.5 [36.5-75.2], P<0.001), and a larger extent of microvascular obstruction (0.3 [0.0-2.2] % LV vs. 0.0 [0.0-1.4] % LV, P=0.01). An elevated shock index was associated with reduced MACE-free survival (P<0.001). Furthermore, the admission shock index was identified as an independent predictor of MACE (hazard ratio=2.92 [1.24-4.22], P<0.01). CONCLUSIONS: STEMI patients with an elevated admission shock index had more pronounced myocardial and microvascular damage. Moreover, the shock index was independently associated with MACE at 12 months. PMID- 26902548 TI - Activation of cross-reactive mucosal T and B cell responses in human nasopharynx associated lymphoid tissue in vitro by Modified Vaccinia Ankara-vectored influenza vaccines. AB - Recent efforts have been focused on the development of vaccines that could induce broad immunity against influenza virus, either through T cell responses to conserved internal antigens or B cell response to cross-reactive haemagglutinin (HA). We studied the capacity of Modified Vaccinia Ankara (MVA)-vectored influenza vaccines to induce cross-reactive immunity to influenza virus in human nasopharynx-associated lymphoid tissue (NALT) in vitro. Adenotonsillar cells were isolated and stimulated with MVA vaccines expressing either conserved nucleoprotein (NP) and matrix protein 1 (M1) (MVA-NP-M1) or pandemic H1N1 HA (MVA pdmH1HA). The MVA vaccine uptake and expression, and T and B cell responses were analyzed. MVA-vectored vaccines were highly efficient infecting NALT and vaccine antigens were highly expressed by B cells. MVA-NP-M1 elicited T cell response with greater numbers of IFNgamma-producing CD4+ T cells and tissue-resident memory T cells than controls. MVA-pdmH1HA induced cross-reactive anti-HA antibodies to a number of influenza subtypes, in an age-dependent manner. The cross-reactive antibodies include anti-avian H5N1 and mainly target HA2 domain. CONCLUSION: MVA vaccines are efficient in infecting NALT and the vaccine antigen is highly expressed by B cells. MVA vaccines expressing conserved influenza antigens induce cross-reactive T and B cell responses in human NALT in vitro, suggesting the potential as mucosal vaccines for broader immunity against influenza. PMID- 26902550 TI - Diagnosis and treatment of lymph node metastases of a rectal carcinoid tumor using In111-octreotide-scintigraphy and intraoperative gamma probe detection. AB - Carcinoids represent 1-2% of the rectal cancer. We report the case of a woman with a rectal carcinoid and a hypogastric node metastasis. We propose a less invasive treatment of the metastase using In11-octreotide-scintigraphy and intraoperative gamma-probe detector. PMID- 26902551 TI - Complete small bowel obstruction secondary to transomental herniation in pregnancy. AB - During pregnancy, abdominal pain can be caused by both obstetric and non obstetric causes. Non-obstetric causes of severe abdominal pain during pregnancy must always be considered. Complete bowel obstruction caused by an internal hernia is rare in obstetric surgical patients. Delays in diagnosis can occur due to non-specific signs and symptoms which can be present in normal pregnancy, and a reluctance to operate on the pregnant patient. Prompt diagnosis and early surgical intervention is the cornerstone for a good outcome. Surgical intervention during pregnancy is associated with increased risk of foetal loss. The use of intra-operative cardiotocography for foetal monitoring in non obstetric surgery remains controversial. PMID- 26902552 TI - An unusual case of a strangulated right inguinal hernia containing the sigmoid colon. AB - The strangulated inguinal hernia is one of the most common emergencies in surgery. Although the diagnosis is usually made by physical examination, the content of the hernia sac and the extent of the following operation may vary. We present an extremely rare case of a strangulated right inguinal hernia containing the sigmoid colon and review the relevant literature. PMID- 26902553 TI - Isolated iliac artery aneurysm rupture presenting as left iliac fossa pain and diarrhoea: A case report. AB - Isolated iliac aneurysm rupture is rare and difficult to diagnose, but needs to be actively considered and excluded. We document the case of a 71 year old female who presented with left iliac fossa pain and diarrhoea and was subsequently found to have a ruptured isolated iliac artery aneurysm. This case demonstrates the importance of urgent diagnostic CT in surgical patients, who present with features of abdominal pain and shock. The key to survival is early diagnosis, appropriate resuscitation and prompt definitive open or endovascular repair. PMID- 26902554 TI - Laparoscopic management of an isolated primary omental hydatid cyst: A case report and literature review. AB - Primary isolated omental hydatid cysts are extremely rare. Usually, omental hydatid cysts are secondary, either resulting from spontaneous spread of cysts or occurring after operations involving hydatidosis in other regions. Here, we report a case of a primary isolated omental hydatid cyst treated with a laparoscopic approach. We report a 16-year-old female who admitted to hospital with right upper quadrant pain. Abdominal ultrasonography and computed tomography (CT) revealed a cyst located between the liver and right kidney. The cyst was enucleated from the omentum and removed with a laparoscopic approach. Histopathologic examination revealed a hydatid cyst. There was no recurrence during 3 years of follow-up. Primary isolated omental hydatid disease should be considered in patients in endemic regions with intra-abdominal cysts. Laparoscopic surgery seems to be effective and safe for hydatid cysts in accessible locations. PMID- 26902555 TI - Severe Raynaud's phenomenon-A streamlined approach to acute management. AB - Raynaud's phenomenon is an exaggerated vasospastic response to cold or emotional stress which not only may cause the patient severe pain but also critical ischaemia and necrosis of the digits. We report the case of a 69-year-old woman who presented with rest pain, impending ulceration and necrosis of finger tips due to an episode of left-sided Raynaud's phenomenon. Intravenous prostacyclin was administered successfully as a bridge to endoscopic thoracic sympathectomy. Vascular surgery units are ideally positioned for the acute management of severe Raynaud's phenomenon to provide continuity of care to patients with profound digital ischaemia and impending tissue loss. PMID- 26902556 TI - Facile Growth of Cu2ZnSnS4 Thin-Film by One-Step Pulsed Hybrid Electrophoretic and Electroplating Deposition. AB - The use of costly and rare metals such as indium and gallium in Cu(In,Ga)Se2 (CIGS) based solar cells has motivated research into the use of Cu2ZnSnS4 (CZTS) as a suitable replacement due to its non-toxicity, abundance of compositional elements and excellent optical properties (1.5 eV direct band gap and absorption coefficient of ~10(4) cm(-1)). In this study, we demonstrate a one-step pulsed hybrid electrodeposition method (PHED), which combines electrophoretic and electroplating deposition to deposit uniform CZTS thin-films. Through careful analysis and optimization, we are able to demonstrate CZTS solar cells with the VOC, JSC, FF and eta of 350 mV, 3.90 mA/cm(2), 0.43 and 0.59%, respectively. PMID- 26902557 TI - Insight and recovery in schizophrenic patients. AB - OBJECTIVE: To investigate the correlation between insight and recovery in schizophrenic patients according to criteria for both symptomatic and functional remission. METHODS: Seventy patients affected by paranoid schizophrenia were recruited and treated with olanzapine, risperidone, aripiprazole, haloperidol and ziprasidone; visits were scheduled at baseline, 12 and 36 months. We administered PANSS (Positive and Negative Syndrome Scale), GAF (Global Assessment of Functioning), SF-36 (Short Form 36 Health Survey), PGWBI (Psychological General Well-Being index) and SAI (Schedule for the Assessment of Insight). RESULTS: After 1 year, 50% of the subjects obtained symptom remission and 25.5% had adequate social functioning for 2 years or more. Only 12% of subjects met full recovery criteria for 2 years or longer. The recovery group also showed an improvement in insight levels, especially patients treated with second-generation antipsychotics (SGA). Recovery was predicted by female sex, higher age, SGA treatment, pre-morbid social adaptation and low level of negative symptoms at baseline. CONCLUSIONS: Only a small proportion of schizophrenic patients achieved recovery, therefore greater patient's insight could have prognostic validity in terms of treatment outcome. More sensitive instruments and a larger sample are necessary to confirm these results. PMID- 26902558 TI - Routine Use of Nonsteroidal Anti-inflammatory Drugs with Corticosteroids in Cataract Surgery: Beneficial or Redundant? PMID- 26902559 TI - The Foundation of Neuro-ophthalmology in the United States of America. PMID- 26902560 TI - Giraffe Pattern of Bilateral Diffuse Uveal Melanocytic Proliferation. PMID- 26902561 TI - Bitot's Spots in Gastric Bypass Patient. PMID- 26902562 TI - Choroidal Macrovessel. PMID- 26902563 TI - En Face: Disappearing Outer Retinal Dots in Treated Syphilitic Chorioretinitis. PMID- 26902564 TI - Solar Retinopathy. PMID- 26902565 TI - Conjunctival Mucoepidermoid Carcinoma. PMID- 26902566 TI - Frosted Branch Angiitis Associated with Cytomegalovirus Retinitis. PMID- 26902568 TI - Reply. PMID- 26902567 TI - Re: Pilat et al.: High-resolution imaging of the optic nerve and retina in optic nerve hypoplasia (Ophthalmology 2015;122:1330-9). PMID- 26902569 TI - Reply. PMID- 26902571 TI - Re: Brodsky et al.: Intermittent exotropia and accommodative esotropia: distinct disorders or two ends of a spectrum? (Ophthalmology 2015;122:1543-6). PMID- 26902570 TI - Re: Veloso et al.: Vitreomacular interface after anti-vascular endothelial growth factor injections in neovascular age-related macular degeneration (Ophthalmology 2015;122:1569-72). PMID- 26902572 TI - Reply. PMID- 26902573 TI - Reply. PMID- 26902574 TI - Re: Watanabe et al.: Relationship between corneal guttae and quality of vision in patients with mild Fuchs' endothelial corneal dystrophy (Ophthalmology 2015;122:2103-9). PMID- 26902575 TI - Reply. PMID- 26902576 TI - Re: Spaide et al.: Volume-rendering optical coherence tomography angiography of macular telangiectasia type 2 (Ophthalmology 2015;122:2261-9). PMID- 26902577 TI - Antischistosomal activity of artemisinin derivatives in vivo and in patients. AB - Schistosomiasis is a helminthic disease affecting more than 200 million people in the tropics as well as returning travellers. Treatment mainly relies on a single drug, praziquantel. Praziquantel cannot kill developing schistosomula resulting in frequent treatment failures and re-infections. Monotherapy also favors the selection for resistance. New drugs are therefore urgently needed. The activity of the semi-synthetic artemisinin derivatives artemether, artesunate and arteether is not restricted to malaria. We reviewed their anti-schistosomal activity in vivo and in patients by searching the PubMed database for publications since 1983 with the search terms "artemisinin" and "Schistosoma". Reports on in vivo studies in animals and clinical trials in human beings were selected. S. mansoni, S. japonicum, and S. haematobium have been tested in mice, rabbits, hamsters, and dogs. These artemisinin derivatives strongly reduced total worm rates with stronger reduction rates for female worms than for males. The drugs also reduced egg burden and egg-caused granulomata in the host liver. Artemisinin-type drugs induced oxidative and metabolic stress leading to morphological damage and decreased fertility of the parasites. Although artemether and artesunate have been investigated in numerous clinical trials, the poor quality of many has led to inconsistent results and has not provided convincing evidence on the therapeutic value against schistosomiasis. Despite these methodological concerns, clinical trials may indicate anti-schistosomal activity in patients. Convincing clinical trials providing unambiguous evidence are now needed. Furthermore, suitable treatment protocols for combination therapy to prevent/treat praziquantel-resistant Schistosoma strains should be investigated. PMID- 26902578 TI - [Not Available]. PMID- 26902579 TI - [Total Pancreatectomy and Islet Autotransplantation in a Child with Recurrent Pancreatitis]. AB - INTRODUCTION: Hereditary pancreatitis in children is rare. The indications for surgery in these children are complications and severe pain that cannot be managed by conservative treatment. Surgical treatment options are duodenum preserving resections as well as drainage procedures. Recurrences are common following theses surgical procedures, because usually the whole pancreas is affected. The majority of the children with symptomatic hereditary pancreatitis are free of pain after total pancreatectomy. When total pancreatectomy is combined with islet autotransplantation, pancreoprivic diabetes can be attenuated or even prevented. The principle of spleen-preserving total pancreatectomy combined with subsequent islet autotransplantation is shown in a case of a 10 year-old child with chronic recurrent pancreatitis in this video. INDICATION: Symptomatic chronic hereditary pancreatitis in children. PROCEDURE: Spleen preserving total pancreatectomy, reconstruction with hepatico-jejunostomy and duodeno-jejunostomy, islet autotransplantation via portal vein. CONCLUSION: If the surgeon has appropriate experience, spleen-preserving total pancreatectomy is a safe procedure. In combination with islet autotransplantation, it may attenuate or prevent diabetes mellitus associated with total pancreatectomy. In highly selected pediatric patients, this surgical procedure has a major benefit compared to a purely symptomatic therapy. PMID- 26902580 TI - [Perioperative Management]. PMID- 26902582 TI - [Typical and Atypical Carcinoids of the Lung: a Surgical Treatment Strategy]. AB - Pulmonary typical (TC) and atypical carcinoids (AC) are lung tumors with neuroendocrine differentiation. Pulmonary carcinoids account for < 2 % of all lung cancers and the incidence is around 0,5/100 000. Depending on localization and extension they present incidentally or symptomatically with cough, hemoptysis and postobstructive pneumonia. Less than 1 % are associated with endocrine activity. TC and AC are differentiated by defined histopathologic criteria (mitotic rate, necrosis). Patients with TC have excellent long-term survival after non-anatomical lung resection. AC are associated with higher recurrence rates and anatomical lung resection should be preferred. Radical mediastinal lymph node dissection should be performed for both TC and AC. Complete surgical resection is the most significant prognostic factor for localized carcinoids. Surgical metastasectomy should also be considered in case of resectable metastatic disease. PMID- 26902583 TI - Stepping back from the guidelines: Where do we stand? AB - The third edition of the autophagy guidelines is now published. This turned out to be a major undertaking in part because of the tremendous increase in the number of researchers participating in autophagy studies, and hence in revising the guidelines. First, I cannot emphasize enough that this paper represents a true community effort-it would simply not be possible for one person to generate such an in-depth and up-to-date manuscript covering this diverse range of topics in the autophagy field. Second, it is of critical importance that this paper indeed does not represent the opinions of a single individual, but rather seeks to obtain a consensus opinion regarding the best methods to monitor autophagy and interpret the results of the corresponding experiments. So, thank you to all who have contributed to the latest version. PMID- 26902585 TI - Differing susceptibility to autophagic degradation of two LC3-binding proteins: SQSTM1/p62 and TBC1D25/OATL1. AB - MAP1LC3/LC3 (a mammalian ortholog family of yeast Atg8) is a ubiquitin-like protein that is essential for autophagosome formation. LC3 is conjugated to phosphatidylethanolamine on phagophores and ends up distributed both inside and outside the autophagosome membrane. One of the well-known functions of LC3 is as a binding partner for receptor proteins, which target polyubiquitinated organelles and proteins to the phagophore through direct interaction with LC3 in selective autophagy, and their LC3-binding ability is essential for degradation of the polyubiquitinated substances. Although a number of LC3-binding proteins have been identified, it is unknown whether they are substrates of autophagy or how their interaction with LC3 is regulated. We previously showed that one LC3 binding protein, TBC1D25/OATL1, plays an inhibitory role in the maturation step of autophagosomes and that this function depends on its binding to LC3. Interestingly, TBC1D25 seems not to be a substrate of autophagy, despite being present on the phagophore. In this study we investigated the molecular basis for the escape of TBC1D25 from autophagic degradation by performing a chimeric analysis between TBC1D25 and SQSTM1/p62 (sequestosome 1), and the results showed that mutant TBC1D25 with an intact LC3-binding site can become an autophagic substrate when TBC1D25 is forcibly oligomerized. In addition, an ultrastructural analysis showed that TBC1D25 is mainly localized outside autophagosomes, whereas an oligomerized TBC1D25 mutant rather uniformly resides both inside and outside the autophagosomes. Our findings indicate that oligomerization is a key factor in the degradation of LC3-binding proteins and suggest that lack of oligomerization ability of TBC1D25 results in its asymmetric localization at the outer autophagosome membrane. PMID- 26902587 TI - Cellular processes underlying cerebral cavernous malformations: Autophagy as another point of view. AB - A growing amount of evidence indicates that autophagy plays a pivotal role in a plethora of human pathological conditions. We have recently broadened the list of the so-called autophagy-related diseases, describing the involvement of defective autophagy in the pathogenesis of cerebral cavernous malformations. PMID- 26902586 TI - Looking at the metabolic consequences of the colchicine-based in vivo autophagic flux assay. AB - Monitoring autophagic flux in vivo or in organs remains limited and the ideal methods relative to the techniques possible with cell culture may not exist. Recently, a few papers have demonstrated the feasibility of measuring autophagic flux in vivo by intraperitoneal (IP) injection of pharmacological agents (chloroquine, leupeptin, vinblastine, and colchicine). However, the metabolic consequences of the administration of these drugs remain largely unknown. Here, we report that 0.8 mg/kg/day IP colchicine increased LC3-II protein levels in the liver of fasted trout, supporting the usefulness of this drug for studying autophagic flux in vivo in our model organism. This effect was accompanied by a decrease of plasma glucose concentration associated with a fall in the mRNA levels of gluconeogenesis-related genes. Concurrently, triglycerides and lipid droplets content in the liver increased. In contrast, transcript levels of beta oxidation-related gene Cpt1a dropped significantly. Together, these results match with the reported role of autophagy in the regulation of glucose homeostasis and intracellular lipid stores, and highlight the importance of considering these effects when using colchicine as an in vivo "autophagometer." PMID- 26902584 TI - Interplay of endoplasmic reticulum stress and autophagy in neurodegenerative disorders. AB - The common underlying feature of most neurodegenerative diseases such as Alzheimer disease (AD), prion diseases, Parkinson disease (PD), and amyotrophic lateral sclerosis (ALS) involves accumulation of misfolded proteins leading to initiation of endoplasmic reticulum (ER) stress and stimulation of the unfolded protein response (UPR). Additionally, ER stress more recently has been implicated in the pathogenesis of HIV-associated neurocognitive disorders (HAND). Autophagy plays an essential role in the clearance of aggregated toxic proteins and degradation of the damaged organelles. There is evidence that autophagy ameliorates ER stress by eliminating accumulated misfolded proteins. Both abnormal UPR and impaired autophagy have been implicated as a causative mechanism in the development of various neurodegenerative diseases. This review highlights recent advances in the field on the role of ER stress and autophagy in AD, prion diseases, PD, ALS and HAND with the involvement of key signaling pathways in these processes and implications for future development of therapeutic strategies. PMID- 26902589 TI - Erratum. PMID- 26902590 TI - Erratum. PMID- 26902588 TI - AMPK-dependent phosphorylation of lipid droplet protein PLIN2 triggers its degradation by CMA. AB - Lipids stored in lipid droplets are hydrolyzed via either cytosolic lipases or a selective form of macroautophagy known as lipophagy. We recently demonstrated that chaperone-mediated autophagy (CMA) is required for the initiation of lipolysis by either of these independent lipolytic pathways. CMA selectively degrades the lipid droplet proteins perilipins (PLIN) 2 and 3 from the lipid droplet surface, thus, facilitating the recruitment of cytosolic lipases and autophagy effector proteins to the lipid droplets. PLIN2 phosphorylation was observed upon induction of lipolysis, but the phosphorylating kinase and the relation of this phosphorylation with CMA of PLIN2 remained unknown. Here, we report that phosphorylation of PLIN2 is dependent on AMPK and occurs after the interaction of PLIN2 with the CMA chaperone HSPA8/Hsc70. Our results highlight a role for posttranslational modifications in priming proteins to be amenable for degradation by CMA. PMID- 26902591 TI - Corrigendum. PMID- 26902592 TI - Corrigendum. PMID- 26902593 TI - New pathway for the formation of metallic cubic phase Ge-Sb-Te compounds induced by an electric current. AB - The novel discovery of a current-induced transition from insulator to metal in the crystalline phase of Ge2Sb2Te5 and GeSb4Te7 have been studied by means of a model using line-patterned samples. The resistivity of cubic phase Ge-Sb-Te compound was reduced by an electrical current (~1 MA/cm(2)), and the final resistivity was determined based on the stress current density, regardless of the initial resistivity and temperature, which indicates that the conductivity of Ge Sb-Te compound can be modulated by an electrical current. The minimum resistivity of Ge-Sb-Te materials can be achieved at high kinetic rates by applying an electrical current, and the material properties change from insulating to metallic behavior without a phase transition. The current-induced metal transition is more effective in GeSb4Te7 than Ge2Sb2Te5, which depends on the intrinsic vacancy of materials. Electromigration, which is the migration of atoms induced by a momentum transfer from charge carriers, can easily promote the rearrangement of vacancies in the cubic phase of Ge-Sb-Te compound. This behavior differs significantly from thermal annealing, which accompanies a phase transition to the hexagonal phase. This result suggests a new pathway for modulating the electrical conductivity and material properties of chalcogenide materials by applying an electrical current. PMID- 26902594 TI - Multiple Sclerosis-related Uveitis: Does MS Treatment Affect Uveitis Course? AB - PURPOSE: Few data are available regarding the optimal treatment of multiple sclerosis (MS)-related uveitis. The aim of this study was to describe clinical features of MS-associated uveitis and determine how MS treatment affects the course of uveitis. METHODS: Retrospective, multicenter study. Patients were divided into two groups according to the use (group 2) or not (group 1) of immunomodulatory drugs. Characteristics of uveitis and treatment were reviewed. RESULTS: A total of 68 eyes from 36 patients (17 in group 1 and 19 in group 2) were included. All patients were treated with topical and/or systemic steroids for uveitis. Uveitis occurred 1-17 years prior to neurologic symptoms in 78% of patients. Uveitis was more severe in group 2 (p<0.05), with a tendency toward a higher rate of chronic uveitis (p = 0.06). CONCLUSIONS: MS-related uveitis has often a favorable evolution. Patients on interferon-beta have more severe and chronic uveitis. As far as we are concerned, interferon-beta given on the sole indication of uveitis is not recommended. If steroid-sparing agent is required for intraocular inflammation, immunosuppressive drugs should be considered. PMID- 26902595 TI - Switchable friction enabled by nanoscale self-assembly on graphene. AB - Graphene monolayers are known to display domains of anisotropic friction with twofold symmetry and anisotropy exceeding 200%. This anisotropy has been thought to originate from periodic nanoscale ripples in the graphene sheet, which enhance puckering around a sliding asperity to a degree determined by the sliding direction. Here we demonstrate that these frictional domains derive not from structural features in the graphene but from self-assembly of environmental adsorbates into a highly regular superlattice of stripes with period 4-6 nm. The stripes and resulting frictional domains appear on monolayer and multilayer graphene on a variety of substrates, as well as on exfoliated flakes of hexagonal boron nitride. We show that the stripe-superlattices can be reproducibly and reversibly manipulated with submicrometre precision using a scanning probe microscope, allowing us to create arbitrary arrangements of frictional domains within a single flake. Our results suggest a revised understanding of the anisotropic friction observed on graphene and bulk graphite in terms of adsorbates. PMID- 26902597 TI - In Nano, Volume 10, Issue 2. PMID- 26902596 TI - Shooting for the Moon: Nanoscale Approaches to Cancer. PMID- 26902598 TI - The effect of a Ta oxygen scavenger layer on HfO2-based resistive switching behavior: thermodynamic stability, electronic structure, and low-bias transport. AB - Reversible resistive switching between high-resistance and low-resistance states in metal-oxide-metal heterostructures makes them very interesting for applications in random access memories. While recent experimental work has shown that inserting a metallic "oxygen scavenger layer" between the positive electrode and oxide improves device performance, the fundamental understanding of how the scavenger layer modifies the heterostructure properties is lacking. We use density functional theory to calculate thermodynamic properties and conductance of TiN/HfO2/TiN heterostructures with and without a Ta scavenger layer. First, we show that Ta insertion lowers the formation energy of low-resistance states. Second, while the Ta scavenger layer reduces the Schottky barrier height in the high-resistance state by modifying the interface charge at the oxide-electrode interface, the heterostructure maintains a high resistance ratio between high- and low-resistance states. Finally, we show that the low-bias conductance of device on-states becomes much less sensitive to the spatial distribution of oxygen removed from the HfO2 in the presence of the Ta layer. By providing a fundamental understanding of the observed improvements with scavenger layers, we open a path to engineer interfaces with oxygen scavenger layers to control and enhance device performance. In turn, this may enable the realization of a non volatile low-power memory technology with concomitant reduction in energy consumption by consumer electronics and offering significant benefits to society. PMID- 26902599 TI - Design and Synthesis of Coumarin Derivatives as Novel PI3K Inhibitors. AB - BACKGROUND: Coumarins possess a broad spectrum of biological activities and are important pharmacophores in drug developments. Since aberrant upregulation of PI3K/Akt signaling is related to uncontrolled tumor cell proliferation, enhanced migration, and adhesion-independent tumor growth, it is of interests to find novel coumarin derivatives as anticancer agents targeting the PI3K/Akt signaling pathway. OBJECTIVE: A variety of coumarin derivatives possessing the pyridinylurea units were designed to increase their potency and isoform selectivity against PI3Ks. METHOD: Novel coumarin analogs 4a-m were were prepared from 5-methylpyridin-2-ylamine in a straightforward way and their growth inhibitory activity against tumor cells was evaluated by a MTT assay. The inhibitory activity against PI3Kalpha, beta, delta and gamma was measured by luminescent assay. Akt phosphorylation inhibition and caspase 3 and PARP activation were measured by Western blot analysis. Apoptosis was measured by staining cells with annexin V-FITC and 7-AAD. RESULTS: In general, these coumarin analogs exhibited good in vitro growth inhibitory activities against tumor K562, Hela, A549 and MCF-7 cells. Some of them showed comparable or better potency than BENC-511. Compounds 4b and 4h were much more potent PI3K inhibitors than S14161 or BENC-511. In addition, 4b was more selective to PI3Kalpha/beta over PI3Kdelta/gamma, while 4h was a selective PI3Kalpha/beta/delta inhibitor. Moreover, 4h could suppress the phosphorylation of Akt and induce K562 cell apoptosis. CONCLUSION: Coumarin derivatives possessing the pyridinylurea units are potential PI3K inhibitors and anticancer agents. These findings will be helpful for the future design of more potent and selective PI3K inhibitors. PMID- 26902600 TI - New, Substituted Derivatives of Dicarboximides and their Cytotoxic Properties. AB - A large group of aminoalkyl and aminoalkanol derivatives of selected dicarboximides were synthesized and characterized by 1HNMR, 13CNMR and ESI MS spectra analysis. The thirty nine new compounds were tested for their cytotoxic properties in human chronic (K562), acute leukemia (HL-60), and cervical cancer cells (HeLa) as well as in normal endothelial cells (HUVEC). The most promising compounds are 4-[2-(dimethylamino)ethyl]-, (diethylamino) ethyl]-, 4-[2 (piperidin-1-yl)ethyl]-, 4-[3-(dimethylamino)propyl]- and 4-[2-hydroxy-3-(propan- 2-ylamino)propyl]- derivatives of 1,7-diethyl-8,9-diphenyl-4 azatricyclo[5.2.1.0(2,6)]dec-8-ene-3,5,10-trione exhibiting high and selective cytotoxicity towards K562 and HL-60 cells (IC50 in the range of 1-10 uM) while being non-toxic towards HUVEC and HeLa cells (IC50> 100 MUM). Moreover, the preliminary studies have showed that 4-[2-(piperidin-1-yl)ethyl]- 1,7-diethyl-8,9 diphenyl-4-azatricyclo [5.2.1.0(2,6)]dec-8-ene-3,5,10-trione induces programmed cell death (apoptosis) in leukemia cells. PMID- 26902601 TI - The Synthetic Oleanane Triterpenoid HIMOXOL Induces Autophagy in Breast Cancer Cells via ERK1/2 MAPK Pathway and Beclin-1 Up-regulation. AB - Autophagy is engaged in tumor growth and progression, but also acts as a cell death and tumor suppression initiator. Naturally-derived compounds and their derivatives constitute a rich source of autophagy modulators. This paper presents the study on the mechanism of action of oleanolic acid derivatives, HIMOXOL and Br-HIMOLID, in MCF7 breast cancer cells. Both compounds reduced MCF7 cell viability more efficiently than the parental compound. It is noteworthy that this effect was specific to MCF7 cancer cells, while in non-cancer MCF-12A cells the cytotoxicity of the studied compounds was significantly lower. Moreover, in contrast to oleanolic acid, the tested compounds were only able to increase autophagy in MCF7 cells. Interestingly, HIMOXOL caused a significantly (p<0.05) higher autophagy rate in MCF7 cells than Br-HIMOLID, as measured by an LC3 immuno identification study. We also found that HIMOXOL upregulated Beclin-1 expression in MCF7 cells. The observed biological activity of the compound contributed to the modulation of the MAPK ERK1/2 pathway that is engaged in the regulation of autophagy signaling. Importantly, we revealed no proapoptotic activity of the compound in the studied cells. However, autophagy induction in MCF7 cancer cells was reflected in the significantly decreased viability of these cells. Thus, we conclude that HIMOXOL (but not Br-HIMOLID) might reveal a significant potential against breast cancer cells, since it might efficiently induce the main autophagy mediator and prognostic factor, BECN1. PMID- 26902602 TI - Circulating Tumor Cells: A New Window for Diagnosis and Evaluation of Cancer. AB - As the ever more critical role of individualized therapy in the cancer treatment and management, circulating tumor cells (CTCs) have caught much attention for providing a promising way in metastases establishment, disease diagnosis and prognosis. Also, their presence has been generally considered as the rationale behind the application of systemic adjuvant chemotherapy. Therefore, CTCs open a new window for the clinical utility, especially for the diagnosis and evaluation of cancer, and move toward personalized medicine. In this review, we summarize the pros and cons of current available technologies for enrichment and detection of CTCs comprehensively. In addition, recent advances in the development of microfluidic and nanotechnology for isolation of CTCs are outlined. Furthermore, circulating tumor microemboli (CTM)-based and telomerase-based assays, the emerging methods for CTC detection and the application of CTCs in the clinic, have also been evaluated. Finally, perspectives and challenges of all these methods in the field of CTCs' isolation and detection are presented. PMID- 26902603 TI - Design Strategies, Structures and Molecular Interactions of Small Molecule Src Inhibitors. AB - In recent years, several small molecules approved by FDA for clinical studies are promising anti-cancer agent. Among the kinases, Abelson Leukaemia (Abl), sarcoma (Src), epidermal growth factor receptor (EGFR) and vascular endotelhial growth factor receptor (VEGFR) are considered as primary molecular targets for selective inhibition and the best successful targeted therapy of tyrosine kinase inhibitors (TKIs) has been achieved in the treatment of Bcr (break point cluster)-Abl leukemia. The majority of type 1 kinase inhibitors target the active conformation of ATP binding site. In consequence of intensive studies on kinases, type 2, type 3 (allosteric) and type 4 (covalent) inhibitors have been discovered beyond the type 1 inhibitors. Although the selectivity is a major problem for type 1 inhibitors, these new type of inhibitors are promising for finding new selective compounds, which may provide other therapeutic options for cancer therapy. They may also be a solution to overcome drug resistance that remains unresolved yet. Threedimensional structural determination provides the development of specific and highly binding properties of compounds. Studying the prediction of a binding mode of inhibitors, homology model developments from kinase- ligand co-crystal structures and isosteric replacements have been used to improve binding properties of inhibitors. In this review, critical results related to the design strategies of kinase specifically targeted to Src and Bcr-Abl kinases and therapeutic potential of novel inhibitors will be evaluated. The readers will be endowed with the functional role of Src and Bcr-Abl kinases that lead inhibitor design, the structural analysis of binding modes of kinase inhibitors, the current progress in terms of therapeutic interventions and the mission of leading groups in the field. PMID- 26902604 TI - L-Canavanine Potentiates Cytotoxicity of Chemotherapeutic Drugs in Human Breast Cancer Cells. AB - BACKGROUND: Due to the high level of argininosuccinate synthase (ASS), a key enzyme for the formation of arginine from citrulline, human breast cancers are often resistant to arginine deprivation therapy. An antimetabolite, Lcanavanine (L-CAV), can be incorporated into proteins in the place of arginine, disturbing protein conformation and leading to cellular death. OBJECTIVES: This study was designed to investigate the potential of L-CAV to enhance the toxicity of chemotherapeutic drugs in the human breast cancer cell line MCF-7, and determine the most favorable drug combination to exert synergistic interaction in the presence or absence of arginine in the medium. METHODS: Combination experiment based on the median-effect principle and mass-action law was conducted using constant ratios of cytotoxic agents as developed by Chou (2006). RESULTS: We observed that L-CAV enhanced the toxicity of cisplatin (CIS) and vinblastine (VIN) in MCF-7, even in the presence of L-ARG. On the other hand, L-CAV potentiated the toxicity of doxorubicin (DOX), paclitaxel (PTX), 5- fluoruracil (5-FU), and amphotericin-B (AMP-B) in cells grown in arginine deprived media. CONCLUSION: We conclude that the combination of L-CAV with CIS or VIN can potentiate the toxicity for breast cancer cells. Thus this report presents a new possibility for treating human breast cancers known to be resistant to arginine deprivation. This initial study requires further investigation in in vivo experiments and exploration of the molecular mechanism of cellular response in human breast cancer. PMID- 26902605 TI - Chronic infection with Toxoplasma gondii induces death of submucosal enteric neurons and damage in the colonic mucosa of rats. AB - Intestinal epithelial secretion is coordinated by the submucosal plexus (SMP). Chemical mediators from SMP regulate the immunobiological response and direct actions against infectious agents. Toxoplasma gondii is a worldwide parasite that causes toxoplasmosis. This study aimed to determine the effects of chronic infection with T. gondii on the morphometry of the mucosa and the submucosal enteric neurons in the proximal colon of rats. Male adult rats were distributed into a control group (n = 10) and an infected group (n = 10). Infected rats received orally 500 oocysts of T. gondii (ME-49). After 36 days, the rats were euthanized and samples of the proximal colon were processed for histology to evaluate mucosal thickness in sections. Whole mounts were stained with methylene blue and subjected to immunohistochemistry to detect vasoactive intestinal polypeptide. The total number of submucosal neurons decreased by 16.20%. Vasoactive intestinal polypeptide-immunoreactive neurons increased by 26.95%. Intraepithelial lymphocytes increased by 62.86% and sulfomucin-producing goblet cells decreased by 22.87%. Crypt depth was greater by 43.02%. It was concluded that chronic infection with T. gondii induced death and hypertrophy in the remaining submucosal enteric neurons and damage to the colonic mucosa of rats. PMID- 26902606 TI - Evaluation of the in vivo leishmanicidal activity of amphotericin B emulgel: An alternative for the treatment of skin leishmaniasis. AB - The American Cutaneous Leishmaniasis (ACL) is an infectious disease that can be fatal. The first line of treatment is pentavalent antimonies. However, due to its potential to develop resistance, Amphotericin B (AmB) started to be used as an alternative medicine. Current treatments are limited, a fact that has led to a growing interesting in developing new therapies. This study aims to evaluate the therapeutic potential in vivo of an amphotericin B + oleic acid (OA) emulgel in the treatment of cutaneous leishmaniasis in an experimental model. Strains of Leishmania major MHOM/IL/80/Friendlin of Leishmania major were used. The animals were inoculated subcutaneously. After the development of leishmanial, nodular or ulcerative lesions, the animals were divided into three groups (control, Group A and Group B) and treated twice a day for twelve days. The weight of the animals was measured and the size of the lesions was observed. A histopathological analysis was performed with skin fragments of lesions and with the spleen of animals treated with different treatments (emulgel, AmB 3% emulgel and AmB 3% plus OA 5% emulgel). It was observed that when subjected to treatment with AmB 3% emulgel during the study period using both formulations, with enhancer and without enhancer, ulcerative lesions regress gradually or even complete cure. The quantification of the average number of parasites recovered from the inoculation site was made after the treatment in each group and the differences were considered significant. The treatment with AmB 3% and OA 5% emulgel had the best in vivo therapeutic response, showing good prospects for cutaneous leishmaniasis therapy as an alternative therapy. PMID- 26902607 TI - mRNA expression characteristics are different in irreversibly atrophic intrinsic muscles of the forepaw compared with reversibly atrophic biceps in a rat model of obstetric brachial plexus palsy (OBPP). AB - In obstetric brachial plexus palsy (OBPP), irreversible muscle atrophy occurs much faster in intrinsic muscles of the hand than in the biceps. To elucidate the mechanisms involved, mRNA expression profiles of denervated intrinsic muscles of the forepaw (IMF) and denervated biceps were determined by microarray using the rat model of OBPP where atrophy of IMF is irreversible while atrophy of biceps is reversible. Relative to contralateral control, 446 dysregulated mRNAs were detected in denervated IMF and mapped to 51 KEGG pathways, and 830 dysregulated mRNAs were detected in denervated biceps and mapped to 52 KEGG pathways. In denervated IMF, 10 of the pathways were related to muscle regulation; six with down-regulated and one with up-regulated mRNAs. The remaining three pathways had both up- and down-regulated mRNAs. In denervated biceps, 13 of the pathways were related to muscle regulation, six with up-regulated and seven with down-regulated mRNAs. Five of the pathways with up-regulated mRNAs were related to regrowth and differentiation of muscle cells. Among the 23 pathways with dysregulated mRNAs, 13 were involved in regulation of neuromuscular junctions. Our results demonstrated that mRNAs expression characteristics in irreversibly atrophic denervated IMF were different from those in reversibly atrophic denervated biceps; dysregulated mRNAs in IMF were associated with inactive pathways of muscle regulation, and in biceps they were associated with active pathways of regrowth and differentiation. Lack of self-repair potential in IMF may be a major reason why atrophy of IMF becomes irreversible much faster than atrophy of biceps after denervation. PMID- 26902608 TI - Combination Therapy with AKT3 and PI3KCA siRNA Enhances the Antitumor Effect of Temozolomide and Carmustine in T98G Glioblastoma Multiforme Cells. AB - BACKGROUND: Glioblastoma multiforme (GBM) is the most malignant and invasive human brain tumor, and it is characterized by a poor prognosis and short survival time. Current treatment strategies for GBM, using surgery, chemotherapy and/or radiotherapy, are ineffective. The PI3K/AKT/PTEN signaling pathway is frequently deregulated in this cancer, and it is connected with regulation of the cell cycle, apoptosis, and autophagy. OBJECTIVES: The current study was undertaken to examine the effect of small interfering RNA (siRNA) targeting the AKT3 and PIK3CA genes on the susceptibility of T98G cells to temozolomide (TMZ) and carmustine (BCNU). METHODS: T98G cells were transfected with AKT3 or PI3KCA siRNA. Transfection efficiency was assessed using flow cytometry and fluorescence microscopy. The influence of AKT3 and PI3KCA siRNA in combination with TMZ and BCNU on T98G cell viability, proliferation, apoptosis, and autophagy was evaluated as well. Alterations in messenger RNA (mRNA) expression of apoptosis related and autophagy-related genes were analyzed using quantitative reverse transcription polymerase chain reaction (QRT-PCR). RESULTS: Transfection of T98G cells with AKT3 or PI3KCA siRNA and exposure to TMZ and BCNU led to a significant reduction in cell viability, accumulation of subG1-phase cells, and reduction of cells in the S and G2/M phases, as well as induction of apoptosis or necrosis, and regulation of autophagy. CONCLUSION: The siRNA-induced AKT3 and PI3KCA mRNA knockdown in combination with TMZ and BCNU inhibited proliferation and induced apoptosis and autophagy in T98G cells. Thus, knockdown of these genes in combination with TMZ and BCNU may offer a novel therapeutic strategy to more effectively control the growth of human GBM cells, but further studies are necessary to confirm a positive phenomenon for the treatment of GBM. PMID- 26902609 TI - Impact of estrogen receptor-beta expression on breast cancer prognosis: a meta analysis. AB - Estrogen receptor (ER)-beta has been discovered for decades; however, its prognostic value in breast cancer patients remains controversial. We aimed to evaluate the impact of ER-beta expression on breast cancer survival. A systematic search of Medline, Embase, and Cochrane Library was performed to identify the association between ER-beta expression and outcomes in early breast cancer patients. Random-effects meta-analysis was conducted to generate combined hazard ratios (HRs) with 95 % confidence intervals (CIs) for overall survival (OS) and disease-free survival (DFS). A total of 6769 patients for ER-beta1, 2295 patients for ER-beta2, and 2271 patients for ER-beta5 from 21 studies were included. ER beta1 protein expression was correlated with both favorable 5-year DFS and OS (HR 0.690, 95 % CI 0.610-0.779; P < 0.001; HR 0.632, 95 % CI 0.533-0.749; P < 0.001), while ER-beta1 mRNA had no significant association with DFS (HR 0.915, 95 % CI 0.581-1.440, P = 0.700). ER-beta2 protein was associated with improved DFS (HR 0.799, 95 % CI 0.644-0.992; P = 0.042), but not OS (HR 0.958, 95 % CI 0.762 1.205; P = 0.712). ER-beta5 protein was not significantly associated with DFS (HR 1.070, 95 % CI 0.810-1.410; P = 0.642). Subgroup analysis showed that higher ER beta1 expression was associated with better 5-year DFS in both ER-alpha positive and negative patients, but the positive association between ER-beta1 expression and 5-year OS was only seen in ER-alpha positive patients. Wild-type ER-beta (ER beta1) and its variant ER-beta2 protein expressions are associated with better survival in early breast cancer patients. The prognostic significance of ER-beta1 for DFS is independent of ER-alpha coexpression, whereas the impact on OS was only in ER-alpha positive breast cancer. PMID- 26902612 TI - Robotic complete mesocolic excision for right-sided colon cancer. AB - Complete mesocolic excision (CME) with central vascular ligation for right-sided colon cancer has been proven to provide superior oncologic outcomes and survival advantage when compared to standard lymphadenectomy [1]. A number of studies comparing conventional laparoscopic versus open CME have shown feasibility and safety of the laparoscopic approach with acceptable oncological profile and postoperative outcomes [2, 3]. The introduction of robotic systems with its technical advantages, including improved vision, better ergonomics and precise dissection, has further revolutionized minimally invasive approach in colorectal surgery. However, there seems to be a relatively slow adoption of robotic approach in the CME technique for right-sided colon cancer. This video demonstrates our detailed operative technique and feasibility for performing right-sided CME robotically. The surgical procedure is performed with a medial-to lateral approach through four 8-mm robotic and one assistant ports. First, the ileocolic vessels are isolated, clipped and transected near their origins. Cephalad dissection continues along the ventral aspect of the superior mesenteric vein. Staying in the embryological planes between the mesocolon and retroperitoneal structures, mesenteric dissection is extended up to the root of the right colic vessels, if present, and the middle colic vessels, which are clipped and divided individually near their origins. After the terminal ileum is transected using an endolinear staple, the colon is mobilized fully from gastrocolic tissue and then from its lateral attachments. The transverse colon is transected under the guidance of near-infrared fluorescence imaging. Creation of an intracorporeal side-to-side ileotransversostomy anastomosis and extraction of the specimen complete the operation. We consider robotic CME to be feasible, safe and oncologically adequate for the treatment of right-sided colon cancer. Its technical advantages may lead to further dissemination of the robotic approach and better standardization of this surgical technique. PMID- 26902610 TI - Interplay of the physical microenvironment, contact guidance, and intracellular signaling in cell decision making. AB - The peritumoral physical microenvironment consists of complex topographies that influence cell migration. Cell decision making, upon encountering anisotropic, physiologically relevant physical cues, has yet to be elucidated. By integrating microfabrication with cell and molecular biology techniques, we provide a quantitative and mechanistic analysis of cell decision making in a variety of well-defined physical microenvironments. We used MDA-MB-231 breast carcinoma and HT1080 fibrosarcoma as cell models. Cell decision making after lateral confinement in 2-dimensional microcontact printed lines is governed by branch width at bifurcations. Cells confined in narrow feeder microchannels prefer to enter wider branches at bifurcations. In contrast, in feeder channels that are wider than the cell body, cells elongate along one side wall of the channel and are guided by contact with the wall to the contiguous branch channel independent of its width. Knockdown of beta1-integrins or inhibition of cellular contractility suppresses contact guidance. Concurrent, but not individual, knockdown of nonmuscle myosin isoforms IIA and IIB also decreases contact guidance, which suggests the existence of a compensatory mechanism between myosin IIA and myosin IIB. Conversely, knockdown or inhibition of cell division control protein 42 homolog promotes contact guidance-mediated decision making. Taken together, the dimensionality, length scales of the physical microenvironment, and intrinsic cell signaling regulate cell decision making at intersections.-Paul, C. D., Shea, D. J., Mahoney, M. R., Chai, A., Laney, V., Hung, W.-C., Konstantopoulos, K. Interplay of the physical microenvironment, contact guidance, and intracellular signaling in cell decision making. PMID- 26902611 TI - Comparison of perioperative and oncologic outcomes between open and laparoscopic liver resection for intrahepatic cholangiocarcinoma. AB - BACKGROUND: Laparoscopic liver resection (LLR) has become an essential method for treating malignant liver tumors. Although the perioperative and oncologic outcomes of LLR in patients with hepatocellular carcinoma have been reported, there are few reports of LLR for intrahepatic cholangiocarcinoma (IHCC). METHODS: Patients who underwent liver resection for T1 or T2 IHCC between March 2010 and March 2015 in Gyeongsang National University Hospital were enrolled. They were divided into open (n = 23) and laparoscopic (n = 14) approaches, and the perioperative and oncologic outcomes were compared. RESULTS: The Pringle maneuver was less frequently used (p = 0.015) and estimated blood loss was lesser (p = 0.006) in the laparoscopic group. There were no significant differences in complication rate (p = 1.000), hospital stay (p = 0.371), tumor size (p = 0.159), lymph node metastasis (p = 0.127), and the number of retrieved lymph nodes (p = 0.553). The patients were followed up for a median of 21 months. The 3-year overall survival (OS) and recurrence-free survival (RFS) rates were 74.7 and 55.2 %, respectively. No differences were observed in the 3-year OS (75.7 vs 84.6 %, p = 0.672) and RFS (56.7 vs 76.9 %, p = 0.456) rates between the open and laparoscopic groups, even after the groups were divided into patients that received liver resection with or without lymph node dissection. CONCLUSION: LLR for IHCC is a treatment modality that should be considered as an option alongside open liver resection in selected patients. PMID- 26902613 TI - Robotic versus laparoscopic left lateral sectionectomy of liver. AB - BACKGROUND: A few studies have reported only short-term outcomes of various robotic and laparoscopic liver resection types; however, published data in left lateral sectionectomy (LLS) have been limited. The aim of this study was to compare the long- and short-term outcomes of robotic and laparoscopic LLS. METHODS: We retrospectively compared demographic and perioperative data as well as postoperative outcomes of robotic (n = 12) and laparoscopic (n = 31) LLS performed between May 2007 and July 2013. Resection indications included malignant tumors (n = 31) and benign lesions (n = 12) including intrahepatic duct (IHD) stones (n = 9). RESULTS: There were no significant differences in perioperative outcomes of estimated blood loss, major complications, or lengths of stay, but operating time was longer in robotic than in laparoscopic LLS (391 vs. 196 min, respectively) and the operation time for IHD stones did not differ between groups (435 vs. 405 min, respectively; p = 0.190). Disease-free (p = 0.463) and overall (p = 0.484) survival of patients with malignancy did not differ between groups. The 2- and 5-year disease-free survival rates were 63.2 and 36.5 %, respectively. However, robotic LLS costs were significantly higher than laparoscopic LLS costs ($8183 vs. $5190, respectively; p = 0.009). CONCLUSIONS: Robotic LLS was comparable to laparoscopic LLS in surgical outcomes and oncologic integrity during the learning curve. Although robotic LLS was more expensive and time intensive, it might be a good option for difficult indications such as IHD stones. PMID- 26902614 TI - Transanal endoscopic microsurgery for rectal cancer: T1 and beyond? An evidence based review. AB - BACKGROUND: The last three decades have witnessed significant improvements in the diagnosis, staging and treatment of rectal cancer leading to a more tailored approach. One of the most clinically relevant advances in this field is represented by transanal endoscopic microsurgery (TEM). Several studies have investigated its role in the treatment of rectal cancer. However, evidence-based recommendations are limited. The aim of this report is to provide an evidence based review of current indications, controversies and future perspectives of TEM in the management of rectal cancer. METHODS: A review of the literature has been performed in PubMed/Medline electronic databases and the Cochrane Library. Quality of evidence was evaluated according to the GRADE system. RESULTS: TEM allows to perform a more accurate en bloc full-thickness local excision of rectal tumors than transanal excision. TEM alone seems to provide similar oncologic results in selected T1sm1 N0 rectal cancers to those achieved by rectal resection and total mesorectal excision (TME), without impairing anorectal function. The oncologic outcomes of neoadjuvant therapy followed by TEM for selected T2 N0 rectal cancers are promising, but this approach is still under evaluation. A word of caution comes from the increased rate of suture dehiscence and rectal pain after TEM. TEM is a promising tool for the surgical treatment of locally advanced rectal cancer as a platform for transanal TME. CONCLUSIONS: Selected T1 rectal cancers with favorable features may be effectively treated with TEM without jeopardizing long-term oncologic outcomes. The lack of adequate lymphadenectomy represents the main concern of this approach for the treatment of rectal cancer. Several approaches are under evaluation to overcome this limitation. PMID- 26902615 TI - Diverting ileostomy in laparoscopic rectal cancer surgery: high price of protection. AB - BACKGROUND: Anastomotic leakage presents the most feared complication after low anterior resection (LAR). A proximal diversion of the gastrointestinal tract is recommended to avoid septic complications of anastomotic leakage. The aim of the present study was to evaluate the benefits and risks of diverting ileostomy (DI) created during laparoscopic LAR because of low rectal cancer. METHODS: This was a retrospective clinical cohort study conducted to assess outcomes of laparoscopic LAR with/without DI in a single institution within a 6-year period. RESULTS: In total, 151 patients were enrolled in the study (73 patients without DI, 78 patients with DI). There were no significant differences between both groups regarding demographic and clinical features. Overall 30-day morbidity rates were significantly lower in patients without DI (23.3 vs. 42.3 %, P = 0.013). Symptomatic anastomotic leakage occurred more frequently in patients without DI (9.6 vs. 2.5 %, P = 0.090); surgical intervention was needed in 6.8 % of patients without DI. Post-operative hospital stay was significantly longer in the group of patients with DI (11.3 +/- 8.5 vs. 8.1 +/- 6.9 days, P = 0.013). Stoma-related complications occurred in 42 of 78 (53.8 %) patients with DI; some patients had more than one complication. Acute surgery was needed in 9 patients (11.5 %) because of DI-related complications. Small bowel obstruction due to DI semi rotation around its longitudinal axis was seen in 3 patients (3.8 %) and presents a distinct complication of DI laparoscopic construction. The mean interval between LAR and DI reversal was more than 8 months; only 19.2 % of patients were reversed without delay (<=4 months). Morbidity after DI reversal was 16.6 %; re laparotomy was necessary in 2.5 % of patients. CONCLUSIONS: The present study indicates that DI protects low rectal anastomosis from septic complications at a cost of many stoma-related complications, substantial risk of acute surgery necessity and long stoma periods coupled with decreased quality of life. PMID- 26902616 TI - Small bowel in vivo bioengineering using an aortic matrix in a porcine model. AB - OBJECTIVE: To evaluate the feasibility of an in vivo small bowel bioengineering model using allogeneic aortic grafts in pigs. BACKGROUND: The best treatment for short bowel syndrome is still unclear. Intestinal transplantation, as well as lifelong parenteral nutrition is associated with a 5-year survival rate of less than 50 %. We have already used allogeneic arterial segments to replace the upper airway in sheep. The results were encouraging with an induced transformation of the aortic wall into tracheo-bronchial bronchial-type tissue. METHODS: Seven young mini-pigs were used. A 10-cm-diameter, allogeneic, aortic graft was interposed in an excluded small bowel segment and wrapped by the neighboring omentum. Animals were autopsied at 1 (n = 2), 3 (n = 3), and 6 months (n = 2), respectively. Specimens were examined macroscopically and microscopically. RESULTS: The overall survival rate of the animals was 71.4 %. No anastomotic leak occurred. Histologic analysis revealed intestinal-like wall transformation of the aortic graft in the surviving animals. CONCLUSION: Aortic-enteric anastomosis is feasible in a porcine model. Moreover, in vivo, bioengineered, intestinal-like transformation of the vascular wall was identified. PMID- 26902617 TI - Red cell distribution width is a novel biomarker that predicts excess body-mass index loss 1 year after laparoscopic Roux-en-Y gastric bypass. AB - INTRODUCTION: Bariatric surgery is the most effective method for producing sustained weight loss, improving obesity-associated comorbidities and reducing inflammation in the morbidly obese population. The red cell distribution width (RDW) is a novel marker of inflammation that is usually reported as part of a complete blood count. In this study, we tested our hypothesis that red cell distribution width might represent a novel biomarker predictive of excess body mass index loss (EBMIL) following laparoscopic Roux-en-Y gastric bypass (LRYGB). METHODS: Five hundred and forty-seven LRYGB patients included from a single institution were individually reviewed, noting both preoperative RDW and percent excess BMI loss at 6 months and 1 year post-LRYGB (%EBMIL180 and %EBMIL365, respectively). Bivariate and multivariate linear regression analysis was conducted between age, gender, initial body-mass index (BMI0) and RDW and each of the two endpoints, to assess the independence of RDW as a predictor of postoperative success. RESULTS: The median RDW was 13.9 (13.3-14.6) %, and median EBMIL180 and EBMIL365 were 55.4 (45.2-66.7) % and 71.3 (58.9-87.8) %, respectively. After controlling for age, gender and BMI0, RDW was associated with %EBMIL365 (B = -1.4 [-2.8 to -0.002] %, P = .05), but not %EBMIL180 (B = -0.6 [ 1.6 to 0.5] %, P = .30. Upon Kruskal-Wallis analysis, patients with a preoperative RDW > 15.0 % had significantly lower %EBMIL than those in the <13.0 % (P < .001) and 13.0-15.0 % (P < .01) strata. CONCLUSIONS: RDW is predictive of EBMIL at 1 year following LRYGB. This represents a novel preoperative biomarker that may provide clinically useful prognostic information. PMID- 26902618 TI - Surgical margin-negative endoscopic mucosal resection with simple three-clipping technique: a randomized prospective study (with video). AB - BACKGROUND: Although endoscopic mucosal resection is an established colorectal polyp treatment, local recurrence occurs in 13 % of cases due to inadequate snaring. We evaluated whether pre-clipping to the muscularis propria resulted in resected specimens with negative surgical margins without thermal denaturation. METHODS: Of 245 polyps from 114 patients with colorectal polyps under 20 mm, we included 188 polyps from 81 patients. We randomly allocated polyps to the conventional injection group (CG) (97 polyps) or the pre-clipping injection group (PG) (91 polyps). The PG received three-point pre-clipping to ensure ample gripping to the muscle layer on the oral and both sides of the tumor with 4 mL local injection. Endoscopic ultrasonography was performed to measure the resulting bulge. Outcomes included the number of instances of thermal denaturation of the horizontal/vertical margin (HMX/VMX) or positive horizontal/vertical margins (HM+/VM+), the shortest distance from tumor margins to resected edges, and the maximum bulge distances from tumor surface to the muscularis propria. RESULTS: The numbers of HMX and HM+ in the CG and PG were 27 and 6, and 9 and 2 (P = 0.001), and VMX and VM+ were 8 and 5, and 0 and 0 (P = 0.057). The shortest distance from tumor margin to resected edge [median (range), mm] in polyps in the CG and PG was 0.6 (0-2.7) and 4.7 (2.1-8.9) (P = 0.018). The maximum bulge distances were 4.6 (3.0-8.0) and 11.0 (6.8-17.0) (P = 0.005). CONCLUSIONS: Pre-clipping enabled surgical margin-negative resection without thermal denaturation. PMID- 26902619 TI - Living biointerfaces based on non-pathogenic bacteria support stem cell differentiation. AB - Lactococcus lactis, a non-pathogenic bacteria, has been genetically engineered to express the III7-10 fragment of human fibronectin as a membrane protein. The engineered L. lactis is able to develop biofilms on different surfaces (such as glass and synthetic polymers) and serves as a long-term substrate for mammalian cell culture, specifically human mesenchymal stem cells (hMSC). This system constitutes a living interface between biomaterials and stem cells. The engineered biofilms remain stable and viable for up to 28 days while the expressed fibronectin fragment induces hMSC adhesion. We have optimised conditions to allow long-term mammalian cell culture, and found that the biofilm is functionally equivalent to a fibronectin-coated surface in terms of osteoblastic differentiation using bone morphogenetic protein 2 (BMP-2) added to the medium. This living bacteria interface holds promise as a dynamic substrate for stem cell differentiation that can be further engineered to express other biochemical cues to control hMSC differentiation. PMID- 26902620 TI - Sirt1 AS lncRNA interacts with its mRNA to inhibit muscle formation by attenuating function of miR-34a. AB - Recent studies demonstrate the functions of long non-coding RNAs (lncRNAs) in mediating gene expression at the transcriptional or translational level. Our previous study identified a Sirt1 antisense (AS) lncRNA transcribed from the Sirt1 AS strand. However, its role and regulatory mechanism is still unknown in myogenesis. Here, functional analyses showed that Sirt1 AS lncRNA overexpression promoted myoblast proliferation, but inhibited differentiation. Mechanistically, Sirt1 AS lncRNA was found to activate its sense gene, Sirt1. The luciferase assay provided evidences that Sirt1 AS lncRNA interacted with Sirt1 3' UTR and rescued Sirt1 transcriptional suppression by competing with miR-34a. In addition, RNA stability assay showed that Sirt1 AS lncRNA prolonged Sirt1 mRNA half-life from 2 to 10 h. Ribonuclease protection assay further indicated that it fully bound to Sirt1 mRNA in the myoblast cytoplasm. Moreover, Sirt1 AS overexpression led to less mouse weight than the control because of less lean mass and greater levels of Sirt1, whereas the fat mass and levels of miR-34a were not altered. Based on the findings, a novel regulatory mechanism was found that Sirt1 AS lncRNA preferably interacted with Sirt1 mRNA forming RNA duplex to promote Sirt1 translation by competing with miR-34a, inhibiting muscle formation. PMID- 26902621 TI - Indications for Augmentation Cystoplasty in the Era of OnabotulinumtoxinA. AB - Overactive bladder (OAB) with or without a neurogenic etiology that is refractory to conventional first-, second-, and third-line therapies is a challenging condition that typically leaves the physician and the patient with few options. Historically, treatment for patients who did not respond to any of the few pharmacologic choices focused on more invasive surgical options--specifically, augmentation cystoplasty (AC). In 2011 and 2013, the Food and Drug Administration (FDA) approved intradetrusor injection of onabotulinumtoxinA for the treatment of neurogenic detrusor overactivity (NDO) and idiopathic detrusor overactivity (IDO), respectively. Since then, a dramatic decline in the use of AC has called into question its utility in the treatment algorithm of this difficult patient population. The purpose of this paper is to review the current body of literature in order to outline the circumstances in which AC is still a relevant therapeutic option. PMID- 26902622 TI - Female Sexual Dysfunction: Is It a Treatable Disease? AB - Female sexual dysfunction affects approximately 40% of women (Sexual problems and distress in United States women: prevalence and correlates; Shifren et al., Obstet Gynecol, 112(5): 970-978, 2008). Due to its multi-factorial etiology, a wide variety of treatments are available that address specific symptoms, but no treatment exists that treats the overall disorder. Significant strides have recently been made in an effort to treat the plethora of symptoms associated with this disorder. The purpose of this article is to provide an overview of recent research on the available treatments for female sexual dysfunction. We discuss novel agents such as flibanserin, as well as various mechanical devices and hormonal treatments aimed at the specific subtypes of female sexual dysfunction. PMID- 26902624 TI - Minimally Invasive ("Mini") Percutaneous Nephrolithotomy: Classification, Indications, and Outcomes. AB - Minimally invasive endoscopic procedures are often employed for the surgical removal of kidney stones. Traditionally, large stones are removed by (standard) percutaneous nephrolithotomy (SPCNL). Although effective for the clearance of large stone burdens, SPCNL is associated with significant morbidity. Therefore, in an effort to reduce this morbidity, while preserving efficacy, mini-PCNL (MPCNL) with a smaller tract size (<20 French) was developed. Several studies suggest that MPCNL has a comparable stone-free rate to SPCNL. However, the question of lower morbidity with MPCNL remains unanswered. In this review, we describe the equipment, indications, and efficacy of MPCNL with particular attention to its value over traditional minimally invasive stone removal techniques. PMID- 26902623 TI - Novel Insights into Molecular Indicators of Response and Resistance to Modern Androgen-Axis Therapies in Prostate Cancer. AB - While androgen ablation remains a mainstay for advanced prostate cancer therapy, nearly all patients will inevitably develop disease escape with time. Upon the development of castration-resistant prostate cancer, other androgen-axis-targeted treatments may be added in an effort to starve the disease of its androgen signaling. Nevertheless, additional androgen-pathway resistance usually develops to these novel hormonal therapies. In this review, we will discuss the resistance mechanisms to modern androgen-axis modulators and how these alterations can influence a patient's response to novel hormonal therapy. We conceptualize these resistance pathways as three broad categories: (1) reactivation of androgen/AR signaling, (2) AR bypass pathways, and (3) androgen/AR-independent mechanisms. We highlight examples of each, as well as potential therapeutic approaches to overcome these resistance mechanisms. PMID- 26902625 TI - Female Bladder Outlet Obstruction. AB - The non-specific symptoms the patients express upon the presentation of female bladder outlet obstruction make it a challenge to diagnose. There are subtle differences between the obstructed patient and those whose bladders are underactive and/or fail to mount a detrusor contraction. These disparities can be extracted through a thorough history and examination. At times, the clinician may utilize nomograms, non-invasive uroflow, and urodynamics with the addition of fluoroscopy to establish the diagnosis of obstruction. Management of the obstruction depends on the nature of the condition, whether functional or anatomical. The increase in the number of sling procedures performed to treat stress urinary incontinence has resulted in a rise in the number of iatrogenic obstructions. The temporal relationship between surgery and obstruction is the key to identifying the problem. PMID- 26902626 TI - Magnetic Resonance Imaging-Ultrasound Fusion-Guided Prostate Biopsy: Review of Technology, Techniques, and Outcomes. AB - Transrectal ultrasound (TRUS)-guided (12-14 core) systematic biopsy of the prostate is the recommended standard for patients with suspicion of prostate cancer (PCa). Advances in imaging have led to the application of magnetic resonance imaging (MRI) for the detection of PCa with subsequent development of software-based co-registration allowing for the integration of MRI with real-time TRUS during prostate biopsy. A number of fusion-guided methods and platforms are now commercially available with common elements in image and analysis and planning. Implementation of fusion-guided prostate biopsy has now been proven to improve the detection of clinically significant PCa in appropriately selected patients. PMID- 26902627 TI - Management of the Recurrent Male Urethral Stricture. AB - Urethral stricture disease negatively impacts quality of life and leads to significant urologic pathology including lower urinary tract symptoms, recurrent urinary tract infections, and potentially more severe sequelae such as detrusor dysfunction, renal failure, urethral carcinoma, and Fournier's gangrene. Open urethral reconstruction is considered a durable and definitive treatment for urethral stricture with lifetime success rates ranging from 75-100%; however, strictures do recur up to 10 years after surgery. Recurrence rates vary by repair type. There also is no agreed-upon modality for recurrence surveillance, but there are many modalities with varying degrees of invasiveness. Recurrent strictures may be managed endoscopically or via open repair. We review stricture recurrence rates, surveillance modalities, risk factors, and management options. PMID- 26902628 TI - Systematic Review of Postgraduate Surgical Education in Low- and Middle-Income Countries. AB - Surgical care is recognized as an important component of public health, however, many low- and middle- income countries (LMICs) are faced with a shortage of trained personnel. In response to this unmet need, many countries have developed local postgraduate training programs in surgery. This study aims to characterize general surgery postgraduate education in LMICs. PubMed, EMBASE, and Global Index Medicus databases were searched for articles related to postgraduate general surgery education in LMICs. Studies in other surgical specialties and those published prior to 1990 were excluded. Data were collected on the characteristics of postgraduate training programs. Sixty-four articles discussed postgraduate surgical education in LMICs. Programs in 34 different countries and 6 different regions were represented. Nine countries were low-income, 12 were low-middle income, and 13 were upper-middle-income countries. Sixty-four articles described aspects of the local postgraduate training program. Prior to postgraduate training, residents complete an undergraduate medical degree with 19 programs describing a pre-training experience such as internship. Surgical curricula were broad-based to prepare trainees to work in low-resource settings. At the completion of postgraduate training, examination formats varied including oral, written, and clinical exams. Postgraduate general surgery programs ranged from 2.5 to 7 years. Postgraduate surgical education is one mechanism to increase surgical capacity in LMICs. Different strategies have been employed to improve surgical education in LMICs and learning from these programs can optimize surgical education across teaching sites. PMID- 26902629 TI - Preventive Measures for Postoperative Bile Leakage After Central Hepatectomy: A Multicenter, Prospective, Observational Study of 101 Patients. AB - BACKGROUND: There are no conclusive measures for preventing postoperative bile leakage (POBL). METHODS: First, 310 patients who underwent hepatectomy were analyzed retrospectively to clarify risk factors for POBL. Then, focusing on operations at high risk of POBL, patients who underwent central hepatectomy were recruited prospectively among 18 institutions, to evaluate various preventive measures for avoiding POBL. The primary endpoint was the frequency of POBL. RESULTS: The retrospective analysis revealed central hepatectomy and repeated hepatectomy to be independent risk factors for POBL. One hundred and one patients undergoing central hepatectomy were enrolled in the prospective study. POBL developed in 13 patients (12.9 %). Intraoperative bile leakage was recognized in 42 of the 101 patients (41.6 %), and 10 of the 42 patients developed POBL (23.8 %). Primary closure of the site of bile leakage and/or biliary drainage tube placement was preferable for preventing POBL in the patients with intraoperative bile leakage. Although 59 patients (58.4 %) did not show intraoperative bile leakage, three patients (5.1 %) developed POBL. In the group without intraoperative bile leakage, treatment with fibrin glue with a polyglycolic acid (PGA) sheet or collagen sheet coated with a fibrinogen and thrombin layer (CSFT) had good results. CONCLUSIONS: Primary closure of the site of bile leakage and/or placement of biliary drainage tubes may be recommended in cases involving intraoperative bile leakage. Treatment with fibrin glue with a PGA sheet and/or CSFT might have preventive effects in patients without intraoperative bile leakage. PMID- 26902630 TI - The Predictive Value of Indocyanine Green Clearance in Future Liver Remnant for Posthepatectomy Liver Failure Following Hepatectomy with Extrahepatic Bile Duct Resection. AB - BACKGROUND: Postoperative liver failure (PHLF) is one of the most common complications following major hepatectomy. The preoperative assessment of future liver remnant (FLR) function is critical to predict the incidence of PHLF. OBJECTIVE: To determine the efficacy of the plasma clearance rate of indocyanine green clearance of FLR (ICGK-F) in predicting PHLF in cases of highly invasive hepatectomy with extrahepatic bile duct resection. METHODS: Five hundred and eighty-five patients who underwent major hepatectomy with extrahepatic bile duct resection, from 2002 to 2014 in a single institution, were evaluated. Among them, 192 patients (33 %) had PHLF. The predictive value of ICGK-F for PHLF was determined and compared with other risk factors for PHLF. RESULTS: The incidence of PHLF was inversely proportional to the level of ICGK-F. With multivariate logistic regression analysis, ICGK-F, combined pancreatoduodenectomy, the operation time, and blood loss were identified as independent risk factors of PHLF. The risk of PHLF increased according to the decrement of ICGK-F (the odds ratio of ICGK-F for each decrement of 0.01 was 1.22; 95 % confidence interval 1.12-1.33; P < 0.001). Low ICGK-F was also identified as an independent risk factor predicting the postoperative mortality. CONCLUSIONS: ICGK-F is useful in predicting the PHLF and mortality in patients undergoing major hepatectomy with extrahepatic bile duct resection. This criterion may be useful for highly invasive hepatectomy, such as that with extrahepatic bile duct resection. PMID- 26902631 TI - What Kind of Incision Should be Used in Thoracic Trauma Patients in Emergent Cases? PMID- 26902632 TI - Are Medical Students Who Want to Become Surgeons Different? An International Cross-Sectional Study. PMID- 26902634 TI - Are We Sure that Blood Transfusion is Associated with Recurrence of Hepatocellular Carcinoma After Hepatectomy? PMID- 26902633 TI - Bile Duct Injuries Indeed Are a Rare, But Much Feared Complication. PMID- 26902635 TI - A duplex DNA-gold nanoparticle probe composed as a colorimetric biosensor for sequence-specific DNA-binding proteins. AB - Using duplex DNA-AuNP aggregates, a sequence-specific DNA-binding protein, SQUAMOSA Promoter-binding-Like protein 12 (SPL-12), was directly determined by SPL-12-duplex DNA interaction-based colorimetric actions of DNA-Au assemblies. In order to prepare duplex DNA-Au aggregates, thiol-modified DNA 1 and DNA 2 were attached onto the surface of AuNPs, respectively, by the salt-aging method and then the DNA-attached AuNPs were mixed. Duplex-DNA-Au aggregates having the average size of 160 nm diameter and the maximum absorption at 529 nm were able to recognize SPL-12 and reached the equivalent state by the addition of ~30 equivalents of SPL-12 accompanying a color change from red to blue with a red shift of the maximum absorption at 570 nm. As a result, the aggregation size grew to about 247 nm. Also, at higher temperatures of the mixture of duplex-DNA-Au aggregate solution and SPL-12, the equivalent state was reached rapidly. On the contrary, in the control experiment using Bovine Serum Albumin (BSA), no absorption band shift of duplex-DNA-Au aggregates was observed. PMID- 26902636 TI - Inhibition of monocarboxylate transporter 1 suppresses the proliferation of glioblastoma stem cells. AB - Recent evidence suggests that a minor subset of cancer cells, termed cancer stem cells (CSCs), have self-renewal and tumorigenic potential. Therefore, the characterization of CSCs is important for developing therapeutic strategies against cancer. Cancer cells rely on anaerobic glycolysis to produce ATP even under normoxic conditions, resulting in the generation of excess acidic substances. Cancer cells maintain a weakly alkaline intracellular pH to support functions. Glioblastoma is an aggressive malignancy with a poor 5-year survival rate. Based on the hypothesis that ion transport-related molecules regulate the viability and function of CSCs, we investigated the expression of ion transport related molecules in glioblastoma CSCs (GSCs). Quantitative RT-PCR analysis showed that monocarboxylate transporter1 (MCT1) were upregulated in GSCs, and inhibition of MCT1 decreased the viability of GSCs compared with that of non GSCs. Our findings indicate that MCT1 is involved in the maintenance of GSCs and is a promising therapeutic target for glioblastoma. PMID- 26902637 TI - Early expression of the receptor for advanced glycation end products in a toxic model produced by 6-hydroxydopamine in the rat striatum. AB - The receptor for advanced glycation end products (RAGE) is commonly involved in different neurodegenerative and inflammatory disorders. The cellular signaling associated to RAGE activation may occur upon binding to different ligands. In this study we investigated whether the toxic model produced by 6-hydroxydopamine (6-OHDA) in rats comprises early noxious responses related to RAGE-mediated signaling cascades. In order to explore a possible interaction between 6-OHDA and RAGE, affinity parameters of RAGE with 6-OHDA were estimated by different means. The possible binding sites of 6-OHDA with the VC1 homodimer for both rat and human RAGE were also modeled. Our results show that the striatal infusion of 6 OHDA recruits RAGE upregulation, as evidenced by an early expression of the receptor. 6-OHDA was also found to bind the VC1 homodimer, although its affinity was moderate when compared to other ligands. This work contributes to the understanding of the role of RAGE activation for 6-OHDA-induced neurotoxicity. PMID- 26902638 TI - Bakuchiol augments MyoD activation leading to enhanced myoblast differentiation. AB - Myoblast differentiation is fundamental to skeletal muscle development and regeneration after injury and defects in this process are implicated in muscle atrophy associated with aging or pathological conditions. MyoD family transcription factors function as mater regulators in induction of muscle specific genes during myoblast differentiation. We have identified bakuchiol, a prenylated phenolic monoterpene, as an inducer of MyoD-mediated transcription and myogenic differentiation. C2C12 myoblasts treated with bakuchiol exhibit enhanced muscle-specific gene expression and myotube formation. A key promyogenic kinase p38MAPK is activated dramatically by bakuchiol which in turn induced the formation of MyoD/E protein active transcription complexes. Consistently, the recruitment of MyoD and Baf60c to the Myogenin promoter is enhanced in bakuchiol treated myoblasts. Furthermore, bakuchiol rescues defective p38MAPK activation and myogenic differentiation caused by Cdo-depletion or in RD rhabdomyosarcoma cells. Taken together, these results indicate that bakuchiol enhances myogenic differentiation through p38MAPK and MyoD activation. Thus bakuchiol can be developed into a potential agent to improve muscular regeneration and repair to treat muscular atrophy. PMID- 26902639 TI - Human serum albumin reduces the potency of acetylcholinesterase inhibitor based drugs for Alzheimer's disease. AB - Human serum albumin (HSA) induced modulation of acetylcholinesterase (AChE) inhibition activity of four well-known cholinergic inhibitors like tacrine hydrochloride (TAC), donepezil hydrochloride monohydrate (DON), (-) Huperzine A (HuPA), eserine (ESE) was monitored quantitatively by Ellman's method. Kinetic analysis of enzyme hydrolysis reaction revealed that while the mechanism of inhibition does not change significantly, the inhibition efficiency changes drastically in presence of HSA, particularly for DON and TAC. However, interestingly, no notable difference was observed in the cases of HuPA and/or ESE. For example, the IC50 value of AChE inhibition increases by almost 135% in presence of ~250 MUM HSA (IC50 = 159 +/- 8 nM) while comparing with aqueous buffer solution of pH 8.0 (IC50 = 68 +/- 4 nM) in DON. On the other hand, the change is almost insignificant (<10%) in case of HuPA under the similar condition. The experimentally observed difference in the extent of modulatory effect was correlated with the sequestration ability of HSA towards different drugs predicted from molecular docking calculations. The result in this study demonstrates the importance to consider the plasma protein binding tendency of a newly synthesized AD drug before claiming its potency over the existing one. Further, development of new and intelligent delivery medium that shields the administered drugs from serum adsorption may reduce the optimal drug dose requirement. PMID- 26902641 TI - Acute bilateral vestibulocochlear neuritis following cultured cell vaccine administration for rabies post-exposure prophylaxis. PMID- 26902640 TI - Karrikins delay soybean seed germination by mediating abscisic acid and gibberellin biogenesis under shaded conditions. AB - Karrikins (KAR) are a class of signal compounds, discovered in wildfire smoke, which affect seed germination. Currently, numerous studies have focused on the model plant Arabidopsis in the KAR research field, rather than on crops. Thus the regulatory mechanisms underlying KAR regulation of crop seed germination are largely unknown. Here, we report that KAR delayed soybean seed germination through enhancing abscisic acid (ABA) biosynthesis, while impairing gibberellin (GA) biogenesis. Interestingly, KAR only retarded soybean seed germination under shaded conditions, rather than under dark and white light conditions, which differs from in Arabidopsis. Phytohormone quantification showed that KAR enhanced ABA biogenesis while impairing GA biosynthesis during the seed imbibition process, and subsequently, the ratio of active GA4 to ABA was significantly reduced. Further qRT-PCR analysis showed that the transcription pattern of genes involved in ABA and GA metabolic pathways are consistent with the hormonal measurements. Finally, fluridone, an ABA biogenesis inhibitor, remarkably rescued the delayed-germination phenotype of KAR-treatment; and paclobutrazol, a GA biosynthesis inhibitor, inhibited soybean seed germination. Taken together, these evidences suggest that KAR inhibit soybean seed germination by mediating the ratio between GA and ABA biogenesis. PMID- 26902642 TI - Connections from the rat dorsal column nuclei (DCN) to the periaqueductal gray matter (PAG). AB - Electrical stimulation of the dorsal columns (DCs; spinal cord stimulation; SCS) has been proposed to treat chronic neuropathic pain. SCS may activate a dual mechanism that would affect both the spinal cord and supraspinal levels. Stimulation of DCs or DC nuclei (DCN) in animals where neuropathic pain has been induced causes activation of brainstem centers including the periaqueductal gray (PAG), which is involved in the endogenous pain suppression system. Biotinylated dextran-amine (BDA) was iontophoretically injected into the DCN to analyze the ascending projection directed to the PAG. Separate injections into the gracile nucleus (GrN) and the cuneate nucleus (CunN) showed BDA-positive fibers terminating in different regions of the contralateral PAG. GrN-PAG afferents terminated in the caudal and middle portions of PAG-l, whereas CunN-PAG fibers terminated in the middle and rostral portions of PAG-l. Based on the DCN somatotopic map, the GrN sends information to the PAG from the contralateral hindlimb and the tail and the CunN from the contralateral forelimb, shoulder, neck and ear. This somatotopic organization is consistent with earlier electrophysiological and PAG stimulation studies. These fibers could form part of the DCs-brainstem-spinal cord loop, which may be involved in the inhibitory effects of SCS on neuropathic pain. PMID- 26902645 TI - Acellular and cellular high-density, collagen-fibril constructs with suprafibrillar organization. AB - Collagen is used extensively for tissue engineering due to its prevalence in connective tissues and its role in defining tissue biophysical and biological signalling properties. However, traditional collagen-based materials fashioned from atelocollagen and telocollagen have lacked collagen densities, multi-scale organization, mechanical integrity, and proteolytic resistance found within tissues in vivo. Here, highly interconnected low-density matrices of D-banded fibrils were created from collagen oligomers, which exhibit fibrillar as well as suprafibrillar assembly. Confined compression then was applied to controllably reduce the interstitial fluid while maintaining fibril integrity. More specifically, low-density (3.5 mg mL(-1)) oligomer matrices were densified to create collagen-fibril constructs with average concentrations of 12.25 mg mL(-1) and 24.5 mg mL(-1). Control and densified constructs exhibited nearly linear increases in ultimate stress, Young's modulus, and compressive modulus over the ranges of 65 to 213 kPa, 400 to 1.26 MPa, and 20 to 150 kPa, respectively. Densification also increased construct resistance to collagenase degradability. Finally, this process was amenable to creating high-density cellularized tissues; all constructs maintained high cell viability (at least 97%) immediately following compression as well as after 1 day and 7 days of culture. This method, which integrates the suprafibrillar assembly capacity of oligomers and controlled fluid reduction by confined compression, supports the rational and scalable design of a broad range of collagen-fibril materials and cell-encapsulated tissue constructs for tissue engineering applications. PMID- 26902643 TI - Human Genetic Variability Contributes to Postoperative Morphine Consumption. AB - High interindividual variability in postoperative opioid consumption is related to genetic and environmental factors. We tested the association between morphine consumption, postoperative pain, and single nucleotide polymorphisms (SNPs) within opioid receptor MU 1 (OPRM1), catechol-O-methyltransferase (COMT), uridine diphosphate glucose-glucuronosyltransferase-2B7, and estrogen receptor (ESR1) gene loci to elucidate genetic prediction of opioid consumption. We analyzed 20 SNPs in 201 unrelated Caucasian patients who underwent abdominal surgery and who were receiving postoperative patient-controlled analgesia-administered morphine. Morphine consumption and pain intensity were dependent variables; age and sex were covariates. A haplotype of 7 SNPs in OPRM1 showed significant additive effects on opioid consumption (P = .007); a linear regression model including age and 9 SNPs in ESR1, OPRM1, and COMT explained the highest proportion of variance of morphine consumption (10.7%; P = .001). The minimal model including 3 SNPs in ESR1, OPRM1, and COMT explained 5% of variance (P = .007). We found a significant interaction between rs4680 in COMT and rs4986936 in ESR1 (P = .007) on opioid consumption. SNPs rs677830 and rs540825 of OPRM1 and rs9340799 of ESR1 were nominally associated with pain Numeric Rating Scale scores. Combinations of genetic variants within OPRM1, COMT, and ESR1 better explain variability in morphine consumption than single genetic variants. Our results contribute to the development of genetic markers and statistical models for future diagnostic tools for opioid consumption/efficacy. PERSPECTIVE: This article presents the efforts dedicated to detect correlations between the genetic polymorphisms and the clinical morphine effect self-administered by patients using a patient-controlled analgesia pump after major surgery. The clinical effect is expressed in terms of morphine consumption and pain scores. REGISTERED ON CLINICALTRIALS.GOV: NCT01233752. PMID- 26902646 TI - Chewing lice of genus Ricinus (Phthiraptera, Ricinidae) deposited at the Zoological Institute of the Russian Academy of Sciences, Saint Petersburg, Russia, with description of a new species. AB - We revised a collection of chewing lice deposited at the Zoological Institute of the Russian Academy of Sciences, Saint Petersburg, Russia. We studied 60 slides with 107 specimens of 10 species of the genus Ricinus (De Geer, 1778). The collection includes lectotype specimens of Ricinus ivanovi Blagoveshtchensky, 1951 and of Ricinus tugarinovi Blagoveshtchensky, 1951. We registered Ricinus elongatus Olfers, 1816 ex Turdus ruficollis, R. ivanovi ex Leucosticte tephrocotis and Ricinus serratus (Durrant, 1906) ex Calandrella acutirostris and Calandrella cheleensis which were not included in Price's world checklist. New records for Russia are R. elongatus ex Turdus ruficollis; Ricinus fringillae De Geer, 1778 ex Emberiza aureola, Emberiza leucocephalos, Emberiza rustica, Passer montanus and Prunella modularis; Ricinus rubeculae De Geer, 1778 ex Erithacus rubecula and Luscinia svecica; Ricinus serratus (Durrant, 1906) ex Alauda arvensis. New records for Kyrgyzstan are R. fringillae ex E. leucocephalos and ex Fringilla coelebs. A new record for Tajikistan is R. serratus ex Calandrella acutirostris. The new species Ricinus vaderi Valan n. sp. is described with Calandra lark, Melanocorypha calandra; from Azerbaijan, as a type host. PMID- 26902644 TI - Subjective Sleep Quality Deteriorates Before Development of Painful Temporomandibular Disorder. AB - There is good evidence that poor sleep quality increases risk of painful temporomandibular disorder (TMD). However, little is known about the course of sleep quality in the months preceding TMD onset, and whether the relationship is mediated by heightened sensitivity to pain. The Pittsburgh Sleep Quality Index was administered at enrollment into the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) prospective cohort study. Thereafter the Sleep Quality Numeric Rating Scale was administered every 3 months to 2,453 participants. Sensitivity to experimental pressure pain and pinprick pain stimuli was measured at baseline and repeated during follow-up of incident TMD cases (n = 220) and matched TMD-free controls (n = 193). Subjective sleep quality deteriorated progressively, but only in those who subsequently developed TMD. A Cox proportional hazards model showed that risk of TMD was greater among participants whose sleep quality worsened during follow-up (adjusted hazard ratio = 1.73, 95% confidence limits = 1.29, 2.32). This association was independent of baseline measures of sleep quality, psychological stress, somatic awareness, comorbid conditions, nonpain facial symptoms, and demographic characteristics. Poor baseline sleep quality was not significantly associated with baseline pain sensitivity or with subsequent change in pain sensitivity. Furthermore the relationship between sleep quality and TMD incidence was not mediated via baseline pain sensitivity or change in pain sensitivity. PERSPECTIVE: Subjective sleep quality deteriorates progressively before the onset of painful TMD, but sensitivity to experimental pain does not mediate this relationship. Furthermore, the relationship is independent of potential confounders such as psychological stress, somatic awareness, comorbid conditions, nonpain facial symptoms, and various demographic factors. PMID- 26902647 TI - Role of Residency Interview Preparatory Activities as a Determinant on Pharmacy Residency Match Rates. AB - PURPOSE: Different strategies have been implemented to assist students in securing residency positions. The purpose of this study was to explore the impact of student participation in residency preparation activities on match rates. METHODS: A retrospective observational study was conducted to explore the effect of participation in residency preparation activities and grade point average (GPA) on residency match rate. Match rates for students participating in the Residency Interview Preparation Seminar (RIPS) or mock interviews (ie, intervention group) were compared with students who participated in neither activity (ie, control group). RESULTS: A total of 118 individuals were included in the comparison. Forty-eight students participated in RIPS (n = 29) or mock interviews (n = 19), while 70 students were in the control group. The intervention group had a statistically larger proportion of students securing residency than the control group (81% vs 57%; P = .009). Match rates between students enrolled in RIPS versus those in the mock interview group were not significant. No statistically significant differences were observed based on GPA. CONCLUSION: Students receiving additional preparation prior to interviews when seeking postdoctoral training were significantly more likely to obtain a residency position. In academic settings with limited resources, mock interviews may be preferred over comprehensive preparatory courses. PMID- 26902648 TI - New and Emerging Evidence on the Use of Second-Generation Direct Acting Antivirals for the Treatment of Hepatitis C Virus in Renal Impairment. AB - Due to the intimate relationship between liver and kidney disease in hepatitis C virus (HCV) infection, treatment options for HCV-positive patients at any stage of chronic kidney disease (CKD) are essential. The availability of second generation, direct-acting antiviral (DAA) combinations has allowed for the advent of interferon-sparing treatment regimens with shorter durations and minimal side effects. While many of the second-generation DAAs are principally metabolized by the hepatic system, dosing in severe renal impairment (creatinine clearance [CrCl] <30 mL/min) or dialysis has remained questionable due to limited experience. New evidence regarding the use of these agents in renal impairment continues to become available, as real-world experience with these treatment regimens is reported. Simeprevir, ledipasvir, paritaprevir, ombitasvir, dasabuvir, and daclatasvir have data to suggest safety in end-stage renal disease. While safety and efficacy with sofosbuvir remains uncertain, data are now available to support utilizing a dose adjustment when glomerular filtration rates are <30 mL/min. Upcoming regimens grazoprevir/elbasvir and daclatasvir/asunaprevir/beclavubir may provide further options for patients with advanced kidney disease, and ongoing studies will continue to provide guidance for this unique patient population. This article will review the currently available literature, including the newest emerging evidence, on the use of second-generation DAAs in CKD stages 3 to 5 and dialysis. PMID- 26902650 TI - Pioglitazone may reduce cardiovascular events in high risk patients with prediabetes. PMID- 26902651 TI - A review on animal models of stroke: An update. AB - Stroke is one of the major healthcare challenges prevailing across the globe due to its significant rate of mortality and morbidity. Stroke is multifactorial in nature and involves several cellular and molecular signaling cascades that make the pathogenesis complex and treatment difficult. For a deeper understanding of the diverse pathological mechanisms and molecular & cellular cascades during stroke, animal modeling serves as a reliable and an effective tool. This also helps to develop and critically analyse various neuroprotective strategies for the mitigation of this devastating disease. Animal modeling for stroke has been revolutionized with the development of newer and more relevant models or approaches that mimic the clinical setting of stroke to a greater extent. This review analyses experimental models of stroke (ischemic and hemorrhagic) and their reliability in stroke situation. Besides this, the review also stresses upon the use of various preclinical models to understand the pathophysiological mechanisms that operate during stroke and to elucidate new, safe and effective neuroprotective agents to combat this life threatening healthcare concern. PMID- 26902649 TI - Pepino (Solanum muricatum) planting increased diversity and abundance of bacterial communities in karst area. AB - Soil nutrients and microbial communities are the two key factors in revegetation of barren environments. Ecological stoichiometry plays an important role in ecosystem function and limitation, but the relationships between above- and belowground stoichiometry and the bacterial communities in a typical karst region are poorly understood. We used pepino (Solanum muricatum) to examine the stoichiometric traits between soil and foliage, and determine diversity and abundance of bacteria in the karst soil. The soil had a relatively high pH, low fertility, and coarse texture. Foliar N:P ratio and the correlations with soil nitrogen and phosphorus suggested nitrogen limitation. The planting of pepino increased soil urease activity and decreased catalase activity. Higher diversity of bacteria was determined in the pepino rhizosphere than bulk soil using a next generation, Illumina-based sequencing approach. Proteobacteria, Acidobacteria, Actinobacteria and Bacteroidetes were the dominant phyla in all samples, accounting for more than 80% of the reads. On a genus level, all 625 detected genera were found in all rhizosphere and bulk soils, and 63 genera showed significant differences among samples. Higher Shannon and Chao 1 indices in the rhizosphere than bulk soil indicated that planting of pepino increased diversity and abundance of bacterial communities in karst area. PMID- 26902654 TI - Effect of doping on the far-infrared intersubband transitions in nonpolar m-plane GaN/AlGaN heterostructures. AB - This paper assesses the effects of Si doping on the properties of nonpolar m plane GaN/AlGaN quantum wells (QWs) designed for intersubband (ISB) absorption in the far-infrared spectral range. For doping levels up to 3 * 10(12) cm(-2), structural analysis reveals uniform QWs with abrupt interfaces and no epitaxially induced defects. Cathodoluminescence spectroscopy confirms the homogeneity of the multiple QWs along the growth direction. Increasing the doping density in the QWs from 1 * 10(11) cm(-2) to 3 * 10(12) cm(-2) induces a broadening of the photoluminescence as well as a reduction of the exciton localization energy in the alloy. Also, enhancement of the ISB absorption is observed, along with a blue shift and widening of the absorption peak. The magnitude of the ISB absorption saturates for doping levels around 1 * 10(12) cm(-2), and the blue shift and broadening increase less than theoretically predicted for the samples with higher doping levels. This is explained by the presence of free carriers in the excited electron level due to the increase of the Fermi level energy. PMID- 26902652 TI - Fibrosis biomarkers in workers exposed to MWCNTs. AB - Multi-walled carbon nanotubes (MWCNT) with their unique physico-chemical properties offer numerous technological advantages and are projected to drive the next generation of manufacturing growth. As MWCNT have already found utility in different industries including construction, engineering, energy production, space exploration and biomedicine, large quantities of MWCNT may reach the environment and inadvertently lead to human exposure. This necessitates the urgent assessment of their potential health effects in humans. The current study was carried out at NanotechCenter Ltd. Enterprise (Tambov, Russia) where large scale manufacturing of MWCNT along with relatively high occupational exposure levels was reported. The goal of this small cross-sectional study was to evaluate potential biomarkers during occupational exposure to MWCNT. All air samples were collected at the workplaces from both specific areas and personal breathing zones using filter-based devices to quantitate elemental carbon and perform particle analysis by TEM. Biological fluids of nasal lavage, induced sputum and blood serum were obtained from MWCNT-exposed and non-exposed workers for assessment of inflammatory and fibrotic markers. It was found that exposure to MWCNTs caused significant increase in IL-1beta, IL6, TNF-alpha, inflammatory cytokines and KL 6, a serological biomarker for interstitial lung disease in collected sputum samples. Moreover, the level of TGF-beta1 was increased in serum obtained from young exposed workers. Overall, the results from this study revealed accumulation of inflammatory and fibrotic biomarkers in biofluids of workers manufacturing MWCNTs. Therefore, the biomarkers analyzed should be considered for the assessment of health effects of occupational exposure to MWCNT in cross-sectional epidemiological studies. PMID- 26902653 TI - Genetic editing of HLA expression in hematopoietic stem cells to broaden their human application. AB - Mismatch of human leukocyte antigens (HLA) adversely impacts the outcome of patients after allogeneic hematopoietic stem-cell transplantation (alloHSCT). This translates into the clinical requirement to timely identify suitable HLA matched donors which in turn curtails the chances of recipients, especially those from a racial minority, to successfully undergo alloHSCT. We thus sought to broaden the existing pool of registered unrelated donors based on analysis that eliminating the expression of the HLA-A increases the chance for finding a donor matched at HLA-B, -C, and -DRB1 regardless of a patient's race. Elimination of HLA-A expression in HSC was achieved using artificial zinc finger nucleases designed to target HLA-A alleles. Significantly, these engineered HSCs maintain their ability to engraft and reconstitute hematopoiesis in immunocompromised mice. This introduced loss of HLA-A expression decreases the need to recruit large number of donors to match with potential recipients and has particular importance for patients whose HLA repertoire is under-represented in the current donor pool. Furthermore, the genetic engineering of stem cells provides a translational approach to HLA-match a limited number of third-party donors with a wide number of recipients. PMID- 26902655 TI - Recognition and management of intra-abdominal hypertension and abdominal compartment syndrome; a survey among Dutch surgeons. AB - PURPOSE: Intra-abdominal hypertension (IAH) and Abdominal compartment syndrome (ACS) are relatively rare, but severe complications. Although many advances were made in recent years, the recognition and management remain subject of debate. The aim of this study was to determine the current state of awareness, knowledge and use of evidence-based medicine regarding IAH and ACS among Dutch surgeons. METHODS: A literature-based and expert consensus survey was developed. One surgeon in every hospital in The Netherlands was asked to complete the online questionnaire. RESULTS: Sixty of 87 (69 %) invited surgeons completed the questionnaire. Intra-abdominal pressure (IAP) was measured using intra-vesical methods by 55 (98 %) respondents. Diuretics (N = 38; 63 %) and laparotomy (N = 33; 55 %) were considered useful treatments for IAH or prevention of ACS by a majority. Only 16 (27 %) respondents used these guidelines in daily practice, and 37 (62 %) respondents are willing to do so. Although 35 (58 %) surgeons agreed that IAH is only a symptom, not requiring treatment. Forty-one percent of experienced respondents suggested that prevalence of ACS remained unchanged. Nearly all respondents (N = 59; 98 %) believed that open abdomen management improves patient outcomes, many (N = 46; 77 %) confirm the high complications rate of this treatment. CONCLUSION: The definitions of IAH and ACS and the related diagnostic and therapeutic challenges are relatively well known by Dutch surgeons. Despite limited use of the evidence-based guidelines, the willingness to do so is high. Most respondents favor open abdomen treatment for patients with imminent ACS, despite the high complication rates associated with this treatment. PMID- 26902656 TI - Bacteriology and antimicrobial susceptibility of ESBLs producers from pus in patients with abdominal trauma associated intra-abdominal infections. AB - PURPOSE: Intra-abdominal infections (IAIs) caused by ESBLs producing bacteria have become a serious clinical concern worldwide as the prevalence of bacterial resistance to antibiotics continues to increase. The objective of this study was to analyze the bacteriology and antimicrobial susceptibility of ESBLs producers using pus samples from IAIs patients caused by abdominal trauma. METHODS: A total of 113 pus samples aspirated from IAIs patients were collected. The BACTEC 9120 and Vitek 2 system were used for detecting positive pathogens and confirming ESBLs production. The results of susceptibility were determined following the Clinical Laboratory Standards Institute guidelines. RESULTS: Among the pathogens causing IAIs, Escherichia coli (E. coli) (29.1 %) was the most commonly isolated, followed by Klebsiella pneumoniae (K. pneumoniae) (22.5 %). The incidence rates of ESBLs production among E. coli, K. pneumoniae, and Klebsiella oxytoca were 69.6, 45.1, and 25.0 %, respectively. All pathogens had high resistance rates against studied antibiotics, with imipenem (88.7 %) and ertapenem (90.7 %) remaining the only practical options. Trend analysis documented an increase in ESBLs producing E. coli and K. pneumoniae, and a decrease in susceptibility for carbapenems among ESBLs producing E. coli and K. pneumoniae. CONCLUSIONS: Escherichia coli and K. pneumoniae were the major pathogens causing abdominal trauma associated IAIs. The most active agents against ESBLs producing E. coli and K. pneumoniae were ertapenem and imipenem. However, the ESBLs rates were alarmingly high and increasing among IAIs associated gram-negative bacilli infections in China, and most agents exhibited decreased susceptibility against ESBLs producing pathogens. PMID- 26902657 TI - Mussel-inspired Functionalization of Cotton for Nano-catalyst Support and Its Application in a Fixed-bed System with High Performance. AB - Inspired by the composition of adhesive and reductive proteins secreted by marine mussels, polydopamine (PDA) was used to coat cotton microfiber (CMF), and then acted as reducing agent for the growth of Pd nanoparticles on PDA coated CMF (PDA@CMF) composites. The resultant CMF@PDA/Pd composites were then packed in a column for the further use in fixed-bed system. For the catalysis of the reduction of 4-nitrophenol, the flow rate of the 4-aminophenol solution (0.5 mM) was as high as 60 mL/min. The obtained fixed-bed system even exhibited superior performance to conventional batch reaction process because it greatly facilitated the efficiency of the catalytic fibers. Consequently, its turnover frequency (TOF) was up to 1.587 min(-1), while the TOF in the conventional batch reaction was 0.643 min(-1). The catalytic fibers also showed good recyclability, which can be recycled for nine successive cycles without a loss of activity. Furthermore, the catalytic system based on CMF@PDA/Pd can also be applied for Suzuki coupling reaction with the iodobenzene conversion up to 96.7%. The strategy to prepare CMF@PDA/Pd catalytic fixed bed was simple, economical and scalable, which can also be applied for coating different microfibers and loading other noble metal nanoparticles, was amenable for automated industrial processes. PMID- 26902659 TI - The way from microscopic many-particle theory to macroscopic hydrodynamics. AB - Starting from the microscopic description of a normal fluid in terms of any kind of local interacting many-particle theory we present a well defined step by step procedure to derive the hydrodynamic equations for the macroscopic phenomena. We specify the densities of the conserved quantities as the relevant hydrodynamic variables and apply the methods of non-equilibrium statistical mechanics with projection operator techniques. As a result we obtain time-evolution equations for the hydrodynamic variables with three kinds of terms on the right-hand sides: reversible, dissipative and fluctuating terms. In their original form these equations are completely exact and contain nonlocal terms in space and time which describe nonlocal memory effects. Applying a few approximations the nonlocal properties and the memory effects are removed. As a result we find the well known hydrodynamic equations of a normal fluid with Gaussian fluctuating forces. In the following we investigate if and how the time-inversion invariance is broken and how the second law of thermodynamics comes about. Furthermore, we show that the hydrodynamic equations with fluctuating forces are equivalent to stochastic Langevin equations and the related Fokker-Planck equation. Finally, we investigate the fluctuation theorem and find a modification by an additional term. PMID- 26902658 TI - PE11, a PE/PPE family protein of Mycobacterium tuberculosis is involved in cell wall remodeling and virulence. AB - The role of the unique proline-glutamic acid (PE)/proline-proline-glutamic acid (PPE) family of proteins in the pathophysiology and virulence of Mycobacterium tuberculosis is not clearly understood. One of the PE family proteins, PE11 (LipX or Rv1169c), specific to pathogenic mycobacteria is found to be over-expressed during infection of macrophages and in active TB patients. In this study, we report that M. smegmatis expressing PE11 (Msmeg-PE11) exhibited altered colony morphology and cell wall lipid composition leading to a marked increase in resistance against various environmental stressors and antibiotics. The cell envelope of Msmeg-PE11 also had greater amount of glycolipids and polar lipids. Msmeg-PE11 was found to have better survival rate in infected macrophages. Mice infected with Msmeg-PE11 had higher bacterial load, showed exacerbated organ pathology and mortality. The liver and lung of Msmeg-PE11-infected mice also had higher levels of IL-10, IL-4 and TNF-alpha cytokines, indicating a potential role of this protein in mycobacterial virulence. PMID- 26902660 TI - Texting for Health Education. PMID- 26902661 TI - Volume dependence of the dielectric properties of amorphous SiO2. AB - Using first principles calculations, the analysis of the dielectric properties of amorphous SiO2 (am-SiO2) was performed. We found that the am-SiO2 properties are volume dependent, and the dependence is mainly induced by the variation of nanoporosity at the atomic scale. In particular, both ionic and electronic contributions to the static dielectric constants are functions of volume with clear trends. Moreover, using the unique parameterization of the dielectric function provided in this work, we predict dielectric functions at imaginary frequencies of different SiO2 polymorphs having similar band gap energies. PMID- 26902663 TI - Development of a directly correlated Raman and uHPLC-MS content uniformity method for dry powder inhalers through statistical design, chemometrics and mathematical modeling. AB - CONTEXT: Content uniformity (CU) is a critical quality attribute measured and monitored throughout the development and commercial supply of pharmaceutical products. Traditional high-performance liquid chromatography (HPLC) methods are time-consuming in both sample preparation and analysis. Thus, a rapid, nondestructive and preparation free spectroscopy based method such as Raman is preferred. OBJECTIVE: Multiple mathematical algorithms were used to establish robust and directly correlated Raman and ultra-HPLC-mass spectrometry (uHPLC-MS) CU methods for the rapid analysis of blends and agglomerates formulated for dry powder inhalers (DPIs). MATERIALS AND METHODS: Model samples included blends of caffeine and lactose; albuterol and lactose; and albuterol and lactose agglomerates. Design of experiments (DoE) was employed to optimize Raman spectra. Multivariate curve resolution (MCR) was leveraged to assess Raman method robustness. Mathematical modeling provided direct method to method correlation by allowing samples to be scanned first for Raman spectra and then dissolved for uHPLC-MS analysis. Several chemometric models were developed and evaluated for the quantitative analysis of CU. RESULTS: The DoE revealed Raman power and exposure time were negatively correlated when optimizing albuterol and caffeine spectra but positively correlated for lactose. MCR revealed regions in which small changes to power and time resulted in an 8-10% change in concentration predictions. A PCR model worked well for the analysis of caffeine blend samples and a PLS model worked best for both albuterol blends and agglomerates. DISCUSSION AND CONCLUSION: Utilization of DoE, chemometrics and mathematical modeling provided a robust and directly correlated CU method for DPIs. PMID- 26902662 TI - Social Environmental Moderators of Long-term Functional Outcomes of Early Childhood Brain Injury. AB - IMPORTANCE: Pediatric traumatic brain injury (TBI) contributes to impairments in behavior and academic performance. However, the long-term effects of early childhood TBI on functioning across settings remain poorly understood. OBJECTIVE: To examine the long-term functional outcomes of early childhood TBI relative to early childhood orthopedic injuries (OIs). We also examine the moderating role of the social environment as defined by parent report and observational measures of family functioning, parenting practices, and home environment. DESIGN, SETTING, AND PARTICIPANTS: A prospective, longitudinal, observational cohort study conducted at each child's home, school, and hospital, including 3 children's hospitals and 1 general hospital in the Midwest. Patients were enrolled in the initial study between January 2003 and October 2006. Follow-ups were completed between January 2010 and April 2015. Fifty-eight children who sustained a TBI (67% of original enrolled cohort) and 72 children who sustained an OI (61% of the original enrolled cohort) were prospectively followed up from shortly after injury (between the ages of 3 and 7 years at enrollment) to an average of 6.7 years after injury, with assessments occurring at multiple points. MAIN OUTCOMES AND MEASURES: Long-term functional outcomes in everyday settings, as assessed through the Child and Adolescent Functional Assessment Scale (CAFAS). RESULTS: Of the 130 children included, the median age for those with OIs was 11.72 years and 11.97, 12.21, and 11.72 years for those with complicated mild, moderate, and severe TBIs, respectively. Children with moderate and severe TBI were rated as having more functional impairments in multiple domains than those with OIs (P < .05). Children with complicated mild TBI had greater impairments in school (odds ratio = 2.93; 95% CI = 1.10-7.82) and with thinking (odds ratio = 15.72; 95% CI = 3.31-74.73) than those with OIs. Functional impairments in children with TBI were more pronounced among children from families with higher levels of permissive (mean CAFAS of 49.71, 35.74, 58.14, and 16.16 for severe TBI, moderate TBI, complicated mild TBI, and OI, respectively, with significant difference between severe TBI and OI [difference = 33.55; P < .001] and complicated mild TBI and OI [difference = 41.98; P < .001]) or authoritarian (mean CAFAS of 56.45, 41.80, 54.90, and 17.12 for severe TBI, moderate TBI, complicated mild TBI, and OI, respectively, with significant difference between severe TBI and OI [difference = 39.33; P < .001], moderate TBI and OI [difference = 24.68; P = .003], and complicated mild TBI and OI [difference = 37.78; P < .001]) parenting or with fewer home resources (mean CAFAS of 69.57, 47.45, 49.00, and 23.81 for severe TBI, moderate TBI, complicated mild TBI, and OI, respectively, with significant difference between severe TBI and OI [difference = 45.77; P < .001], moderate TBI and OI [difference = 23.64; P < .001], and complicated mild TBI and OI [difference = 25.20; P < .001]). CONCLUSIONS AND RELEVANCE: Even children with relatively mild early TBI experience long-term functional impairments, particularly in the context of less favorable home environments. These findings suggest that improving parenting skills and the quality of the home environment may promote functional recovery following early TBI. PMID- 26902665 TI - N-Arylation of Tertiary Amines under Mild Conditions. AB - A transition-metal-free procedure for the N-arylation of tertiary amines to sp(3) quaternary ammonium salts is described. The presented conditions allow for the isolation of trialkylaryl, dialkyldiaryl, and novel triarylalkyl ammonium salts, including N-chiral quaternary ammonium salts. The reaction works at room temperature, open to air with electron-rich or -poor benzyne precursors and different tertiary amines, allowing the synthesis of a broad range of N-aryl ammonium salts that have applications in a variety of fields. PMID- 26902664 TI - Combining brain stimulation and video game to promote long-term transfer of learning and cognitive enhancement. AB - Cognitive training offers the potential for individualised learning, prevention of cognitive decline, and rehabilitation. However, key research challenges include ecological validity (training design), transfer of learning and long-term effects. Given that cognitive training and neuromodulation affect neuroplasticity, their combination could promote greater, synergistic effects. We investigated whether combining transcranial direct current stimulation (tDCS) with cognitive training could further enhance cognitive performance compared to training alone, and promote transfer within a short period of time. Healthy adults received real or sham tDCS over their dorsolateral prefrontal cortices during two 30-minute mathematics training sessions involving body movements. To examine the role of training, an active control group received tDCS during a non mathematical task. Those who received real tDCS performed significantly better in the game than the sham group, and showed transfer effects to working memory, a related but non-numerical cognitive domain. This transfer effect was absent in active and sham control groups. Furthermore, training gains were more pronounced amongst those with lower baseline cognitive abilities, suggesting the potential for reducing cognitive inequalities. All effects associated with real tDCS remained 2 months post-training. Our study demonstrates the potential benefit of this approach for long-term enhancement of human learning and cognition. PMID- 26902667 TI - Determining optimal cadence for an individual road cyclist from field data. AB - The cadence that maximises power output developed at the crank by an individual cyclist is conventionally determined using a laboratory test. The purpose of this study was two-fold: (i) to show that such a cadence, which we call the optimal cadence, can be determined using power output, heart-rate, and cadence measured in the field and (ii) to describe methodology to do so. For an individual cyclist's sessions, power output is related to cadence and the elicited heart rate using a non-linear regression model. Optimal cadences are found for two riders (83 and 70 revolutions per minute, respectively); these cadences are similar to the riders' preferred cadences (82-92 rpm and 65-75 rpm). Power output reduces by approximately 6% for cadences 20 rpm above or below optimum. Our methodology can be used by a rider to determine an optimal cadence without laboratory testing intervention: the rider will need to collect power output, heart-rate, and cadence measurements from training and racing sessions over an extended period (>6 months); ride at a range of cadences within those sessions; and calculate his/her optimal cadence using the methodology described or a software tool that implements it. PMID- 26902666 TI - Human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine for the prevention of cervical cancer and HPV-related diseases. AB - Vaccines are available against human papillomavirus (HPV), the causal agent of cervical and other cancers. Efficacy data from the HPV-16/18 AS04-adjuvanted vaccine clinical trial program were reviewed. Six randomized, controlled phase II/III trials evaluating cervical endpoints enrolled women from diverse populations and geographical locations. The program analyzed extensively the cohorts most relevant from a public health perspective: the total vaccinated cohort (TVC), approximating a general population including those with existing or previous HPV infection, and TVC-naive, approximating a population of young women before sexual debut. Results show that the vaccine reduces HPV-16/18 infection and associated cervical endpoints in women regardless of age, location, or sexual experience. It provides cross-protection against some non-vaccine oncogenic HPV types and types causing genital warts, and may be effective against vulvar, oral, and anal HPV infection. Early epidemiology data following its introduction suggest a decline in the prevalence of vaccine and some non-vaccine HPV types. PMID- 26902668 TI - Hydrodeoxygenation of prairie cordgrass bio-oil over Ni based activated carbon synergistic catalysts combined with different metals. AB - Bio-oil can be upgraded through hydrodeoxygenation (HDO). Low-cost and effective catalysts are crucial for the HDO process. In this study, four inexpensive combinations of Ni based activated carbon synergistic catalysts including Ni/AC, Ni-Fe/AC, Ni-Mo/AC and Ni-Cu/AC were evaluated for HDO of prairie cordgrass (PCG) bio-oil. The tests were carried out in the autoclave under mild operating conditions with 500psig of H2 pressure and 350 degrees C temperature. The catalysts were characterized by X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET) and transmission electron microscope (TEM). The results show that all synergistic catalysts had significant improvements on the physicochemical properties (water content, pH, oxygen content, higher heating value and chemical compositions) of the upgraded PCG bio-oil. The higher heating value of the upgraded bio-oil (ranging from 29.65MJ/kg to 31.61MJ/kg) improved significantly in comparison with the raw bio-oil (11.33MJ/kg), while the oxygen content reduced to only 21.70-25.88% from 68.81% of the raw bio-oil. Compared to raw bio-oil (8.78% hydrocarbons and no alkyl-phenols), the Ni/AC catalysts produced the highest content of gasoline range hydrocarbons (C6-C12) at 32.63% in the upgraded bio-oil, while Ni-Mo/AC generated the upgraded bio-oil with the highest content of gasoline blending alkyl-phenols at 38.41%. PMID- 26902669 TI - Effect of fungal mycelia on the HPLC-UV and UV-vis spectrophotometric assessment of mycelium-bound epoxide hydrolase using glycidyl phenyl ether. AB - The use of mycelia as biocatalysts has technical and economic advantages. However, there are several difficulties in obtaining accurate results in mycelium catalysed reactions. Firstly, sample extraction, indispensable because of the presence of mycelia, can bring into the extract components with a similar structure to that of the analyte of interest; secondly, mycelia can influence the recovery of the analyte. We prepared calibration standards of 3-phenoxy-1,2 propanediol (PPD) in the pure solvent and in the presence of mycelia (spiked before or after extraction) from five fungi (Aspergillus niger, Aspergillus tubingensis, Penicillium aurantiogriseum, Penicillium sp. and Aspergillus terreus). The quantification of PPD was carried out by HPLC-UV and UV-vis spectrophotometry. The manuscript shows that the last method is as accurate as the HPLC method. However, the colorimetric method led to a higher data throughput, which allowed the study of more samples in a shorter time. Matrix effects were evaluated visually from the plotted calibration data and statistically by simultaneously comparing the intercept and slope of calibration curves performed with solvent, post-extraction spiked standards and pre extraction spiked standards. Significant differences were found between the post- and pre-extraction spiked matrix-matched functions. Pre-extraction spiked matrix matched functions based on A. tubingensis mycelia, selected as the reference, were validated and used to compensate for low recoveries. These validated functions were successfully applied to the quantification of PPD achieved during the hydrolysis of glycidyl phenyl ether by mycelium-bound epoxide hydrolases and equivalent hydrolysis yields were determined by HPLC-UV and UV-vis spectrophotometry. This study may serve as starting point to implement matrix effects evaluation when mycelium-bound epoxide hydrolases are studied. PMID- 26902670 TI - Large-scale bioprospecting of cyanobacteria, micro- and macroalgae from the Aegean Sea. AB - Marine organisms constitute approximately one-half of the total global biodiversity, being rich reservoirs of structurally diverse biofunctional components. The potential of cyanobacteria, micro- and macroalgae as sources of antimicrobial, antitumoral, anti-inflammatory, and anticoagulant compounds has been reported extensively. Nonetheless, biological activities of marine fauna and flora of the Aegean Sea have remained poorly studied when in comparison to other areas of the Mediterranean Sea. In this study, we screened the antimicrobial, antifouling, anti-inflammatory and anticancer potential of in total 98 specimens collected from the Aegean Sea. Ethanol extract of diatom Amphora cf capitellata showed the most promising antimicrobial results against Candida albicans while the extract of diatom Nitzschia communis showed effective results against Gram positive bacterium, S. aureus. Extracts from the red alga Laurencia papillosa and from three Cystoseira species exhibited selective antiproliferative activity against cancer cell lines and an extract from the brown alga Dilophus fasciola showed the highest anti-inflammatory activity as measured in primary microglial and astrocyte cell cultures as well as by the reduction of proinflammatory cytokines. In summary, our study demonstrates that the Aegean Sea is a rich source of species that possess interesting potential for developing industrial applications. PMID- 26902671 TI - Pseudosuccinea columella: experimental co-infections of juvenile and pre-adult snails with the digeneans Calicophoron daubneyi and Fasciola hepatica. AB - Experimental co-infections of juvenile and pre-adult Pseudosuccinea columella with Calicophoron daubneyi and Fasciola hepatica (five miracidia of each digenean per snail) were carried out to determine the aptitude of this lymnaeid to ensure complete larval development of the former parasite, the latter or both. Snails infected with F. hepatica were found in the two groups of juveniles, i.e. 1 and 2 mm at exposure, and the four groups of pre-adults, i.e. 3-6 mm. The highest frequency of F. hepatica, i.e. 37.3%, was noted in the 4 mm group. Low frequencies were noted for C. daubneyi and co-infections of both digeneans in the 3, 4 and 5 mm groups. Two other groups of P. columella, measuring 3 and 4 mm at exposure, were also constituted to study the characteristics of these co infections. Compared to controls infected only with F. hepatica, the frequency of this digenean infection and the mean number of metacercariae were significantly lower in co-infected snails, while the patent period was significantly shorter. In snails harbouring C. daubneyi only or both digeneans, lower values were noted for prevalence, the patent period and the number of metacercariae. Pre-adult P. columella (3-5 mm in shell height at exposure) were able to sustain larval development of C. daubneyi if they were co-infected with the sequence C. daubneyi +F. hepatica. Low values noted for the prevalence of C. daubneyi infection and the number of metacercariae would be in favour of a still incomplete adaptation between the snail population and the miracidial isolate. PMID- 26902672 TI - Coping with type 1 diabetes through emerging adulthood: Longitudinal associations with perceived control and haemoglobin A1c. AB - OBJECTIVE: This study, which is part of a larger longitudinal study focusing on the biopsychosocial functioning of emerging adults with type 1 diabetes, examined how perceived personal control, coping and HbA1c relate to one another over time. DESIGN AND MAIN OUTCOME MEASURES: Emerging adults with type 1 diabetes (18-30 years old) participated in a two-wave longitudinal study spanning five years (N = 164 at Time 1). At both times, patients completed questionnaires on perceived control and coping (i.e. diabetes integration, avoidant coping and passive resignation). HbA1c values were obtained from treating clinicians. We investigated the directionality of effects using cross-lagged path analysis. RESULTS: Higher HbA1c values predicted relative decreases in diabetes integration and increases in avoidant coping five years later. Feeling less in control over diabetes predicted the use of passive coping over time. Passive coping predicted a relative decrease in perceived control five years later. CONCLUSION: These findings indicate that tackling poor glycaemic control is not only important to avoid medical complications but also to prevent patients from resorting to more avoidant coping strategies. Furthermore, given the longitudinal interplay between perceived control and passive coping, it is important that intervention efforts include both cognitive and behavioural components to be effective. PMID- 26902673 TI - Retracted: Cure of Chronic Viral Infection and Virus-Induced Type 1 Diabetes by Neutralizing Antibodies. AB - [This retracts the article DOI: 10.1080/17402520600579028.]. PMID- 26902674 TI - Classroom Journal Club: Collaborative Study of Contemporary Primary Literature in the Biomechanics Classroom. AB - Current engineering pedagogy primarily focuses on developing technical proficiency and problem solving skills; the peer-review process for sharing new research results is often overlooked. The use of a collaborative classroom journal club can engage students with the excitement of scientific discovery and the process of dissemination of research results, which are also important lifelong learning skills. In this work, a classroom journal club was implemented and a survey of student perceptions spanning three student cohorts was collected. In this collaborative learning activity, students regularly chose and discussed a recent biomechanics journal article, and were assessed based on specific, individual preparation tasks. Most student-chosen journal articles were relevant to topics discussed in the regular class lecture. Surveys assessed student perceptions of the activity. The survey responses show that, across all cohorts, students both enjoyed the classroom journal club and recognized it as an important learning experience. Many reported discussing their journal articles with others outside of the classroom, indicating good engagement. The results demonstrate that student engagement with primary literature can foster both technical knowledge and lifelong learning skills. PMID- 26902675 TI - Influence of Intimate Partner Violence on Domestic Relocation in Metropolitan and Non-Metropolitan Young Australian Women. AB - Data from a national, population-based longitudinal study of Australian women (26 34 years) were analyzed to investigate the association between domestic relocation and multiple explanatory factors, namely intimate partner violence (IPV), metropolitan versus non-metropolitan residence, education, income, housing tenure, number of children, and changes in relationship status. Experience of IPV in the past 12 months was significantly associated with increased odds of domestic relocation. This association remained significant after controlling for age, social support, area of residence, income, number of children, education, and housing situation. Change in relationship status attenuated the association between recent IPV and domestic relocation. Metropolitan versus non-metropolitan residence had no major influence on these results. PMID- 26902676 TI - Domestic Violence and Abortion Among Rural Women in Four Indian States. AB - The prevalence of domestic violence and abortion in India is high, yet little is known about the relationship between these experiences. Data from two linked data sets, India's 1998-1999 National Family Health Survey (NFHS-2) and a follow-up survey in 2002-2003, were analyzed. The analysis examines how the experience of physical violence affects the subsequent uptake of abortion, and how the experience of abortion affects subsequent experience of physical, sexual, and verbal violence. Women who experienced physical violence have significantly higher odds of reporting a subsequent induced abortion, whereas women who had an induced abortion have significantly higher odds of reporting subsequent sexual and verbal violence. There was no significant relationship between domestic violence and spontaneous abortion. PMID- 26902677 TI - A facile synthesis of Fe3C@mesoporous carbon nitride nanospheres with superior electrocatalytic activity. AB - We report a colloidal amphiphile-templating approach to preparing nanosized Fe3C encapsulated within mesoporous nitrogen-doped carbon nanospheres (Fe3C@mCN). The obtained Fe3C@mCN hybrids having a high surface area and ultrafine Fe3C nanocrystals exhibited superior activity and durability for oxygen reduction. PMID- 26902678 TI - Voxel-based Histographic Analysis of the Basilar Artery in Patients with Isolated Pontine Infarction. AB - BACKGROUND AND PURPOSE: The signal information per voxels of magnetic resonance imaging (MRI) for vessel wall could reflect the pathologic features of atherosclerotic vessels. The aim of this study is to evaluate the usefulness of magnetic resonance voxel-based histogram (VBH) of atherosclerotic basilar artery in patients with isolated pontine infarctions (PIs). MATERIALS AND METHODS: Wall and lumen of basilar artery were segmented from high resolution MR of 42 patients with isolated PI and 10 normal volunteers. VBHs were obtained after normalization by dividing the intensity of segmented wall with the intensity of non-infarcted area of pons. The variables of VBH included area (A), mean signal intensity (SI), standard deviation (SD), kurtosis (K), and skewness (SK) and area stenosis [AS; Awall/(Awall + Alumen)] were compared according to the MRI-modified American Heart Association (AHA) atherosclerotic plaque schema, and between the subgroups of PI (lacunar: LPI and paramedian: PPI). RESULTS: According to the MRI-modified AHA atherosclerotic plaque schema, Awall/T1 (mean area of wall on T1-weighted MRI), SIwall/T1, SDwall/T1, SKwall/T1, Kwall/T1, Alumen/T1, and AST1 showed statistical differences. AHA IV-VII showed higher Awall/T1, SIwall/T1, and AST1 than normal control. PPI showed statistical differences in Awall/T1, SIwall/T1, SK wall/T1, and Awall/T2 than those of normal control after post hoc test, whereas LPI in Awall/T1 and Awall/T2 (P < 0.05, Kruskal-Wallis test, Dunnett T3 procedure). CONCLUSIONS: VBH analysis can provide the quantitative information with regard to volume as well as composition of the atherosclerotic plaque in the basilar artery. The difference in patterns of VBH might be further useful in characterizing PIs with presumably different pathogenesis. PMID- 26902679 TI - Fat-suppressed MR Imaging of the Spine for Metal Artifact Reduction at 3T: Comparison of STIR and Slice Encoding for Metal Artifact Correction Fat suppressed T2-weighted Images. AB - PURPOSE: To compare short tau inversion recovery (STIR) images with slice encoding for metal artifact correction (SEMAC)-corrected magnetic resonance imaging (MRI) of spectral presaturation with inversion recovery (SPIR) or inversion recovery (IR) at 3T in patients with metallic spinal instrumentation. METHODS: Following institutional review board's approval, 71 vertebrae with interbody fixation in 26 patients who underwent transpedicular spondylodesis with spinal metallic prostheses were analyzed with SEMAC spinal MRI. All the fixated vertebrae were examined with STIR, and 41 vertebrae of 15 patients were scanned with SEMAC-SPIR T2-weighted MRI. The remaining 30 vertebrae of 11 patients were scanned with SEMAC-IR T2-weighted MRI. Two musculoskeletal radiologists compared the image sets and qualitatively analyzed the images with a five-point scale that included artifact reduction around the metallic implant and visualization of the rod and pedicle. Quantitative assessments were performed by calculating the signal intensity ratio of the fixated vertebra and non-metallic vertebra and by calculating the signal-to-noise ratios (SNRs) of the vertebrae. A paired t-test was used for the statistical analyses. RESULTS: The SEMAC-IR MRI had a significant decrease in the metallic artifact area (P < 0.05), while the SEMAC SPIR MRI yielded significantly increased artifact areas (P < 0.05). However, the signal intensity ratios (i.e., metal-induced signal pile-up) were not significantly different (P > 0.05) between the STIR and SEMAC MRI. The SNR of the SEMAC MRI was significantly lower than the SNR of the STIR (P < 0.05). The metal artifact reduction scores were significantly higher in the SEMAC-SPIR MRI (P < 0.05). CONCLUSION: Despite the relatively larger artifact size and lower SNRs, the SEMAC-SPIR MRI was superior to the other types of fat-suppressed MRI of SEMAC IR or T2-weighted STIR MRI. However, the drawbacks of high signal pile-up, large artifact size, and relatively low SNRs require further investigation to determine the best method for fat-suppressed MRI of metallic implants. PMID- 26902680 TI - The evolving role of lenalidomide in non-Hodgkin lymphoma. AB - Recent advances in the treatment of patients with non-Hodgkin lymphoma have driven a paradigm shift from standard chemotherapy to an ever-expanding choice of targeted agents and combinations. As an orally bioavailable immunomodulator with antineoplastic, immunologic, and antiproliferative activity in B-cell lymphoma, lenalidomide has emerged as one such option. Lenalidomide demonstrates clinically significant activity with a favorable safety profile as a single agent, as well as in combination therapy. Herein, we review accumulated clinical data on lenalidomide, with particular reference to patients with first-line and relapsed/refractory mantle cell lymphoma, indolent lymphoma, and diffuse large B cell lymphoma. PMID- 26902682 TI - Recent advances in mesoporous silica nanoparticles for antitumor therapy: our contribution. AB - Since 2001, when our research group proposed for the first time MCM-41 as a drug release system, the scientific community has demonstrated a growing interest in mesoporous silica nanoparticles (MSNs) for their revolutionary potential in nanomedicine. Among the diverse pathologies that can be treated with MSNs, cancer has received increasing attention. MSNs can be loaded with large amounts of therapeutic cargoes and once intravenously administrated preferentially accumulate in solid tumours via the enhanced permeation and retention (EPR) effect. Herein we report the recent developments achieved by our research group as a pioneer in this field, highlighting: the design of sophisticated MSNs as stimuli-responsive drug delivery systems to release the entrapped cargo upon exposure to a given stimulus while preventing the premature release of highly cytotoxic drugs before reaching the target; transporting non-toxic prodrugs and the enzyme responsible for its conversion into cytotoxic agents into the same MSNs; improving the selectivity and cellular uptake by cancer cells by active targeting of MSNs; increasing the penetration of MSNs within the tumour mass, which is one of the major challenges in the use of NPs to treat solid tumours. PMID- 26902681 TI - Investigation on the effects of the atmospheric pressure plasma on wound healing in diabetic rats. AB - It is estimated that 15 percent of individuals with diabetes mellitus suffer from diabetic ulcers worldwide. The aim of this study is to present a non-thermal atmospheric plasma treatment as a novel therapy for diabetic wounds. The plasma consists of ionized helium gas that is produced by a high-voltage (8 kV) and high frequency (6 kHz) power supply. Diabetes was induced in rats via an intravascular injection of streptozotocin. The plasma was then introduced to artificial xerograph wounds in the rats for 10 minutes. Immunohistochemistry assays was performed to determine the level of transforming growth factor (TGF-beta1) cytokine. The results showed a low healing rate in the diabetic wounds compared with the wound-healing rate in non-diabetic animals (P < 0.05). Moreover, the results noted that plasma enhanced the wound-healing rate in the non-diabetic rats (P < 0.05), and significant wound contraction occurred after the plasma treatment compared with untreated diabetic wounds (P < 0.05). Histological analyses revealed the formation of an epidermis layer, neovascularization and cell proliferation. The plasma treatment also resulted in the release of TGF beta1 cytokine from cells in the tissue medium. The findings of this study demonstrate the effect of plasma treatment for wound healing in diabetic rats. PMID- 26902683 TI - The efficiency of a new hydrodynamic cavitation pilot system on Artemia salina cysts and natural population of copepods and bacteria under controlled mesocosm conditions. AB - A study of the efficiency of hydrodynamic cavitation and separation was carried out to evaluate an innovative, environmentally safe and acceptable system for ballast water treatment for reducing the risk of introducing non-native species worldwide. Mesocosm experiments were performed to assess the morphological changes and viability of zooplankton (copepods), Artemia salina cysts, and the growth potential of marine bacteria after the hydrodynamic cavitation treatment with a different number of cycles. Our preliminary results confirmed the significant efficiency of the treatment since more than 98% of the copepods and A. salina cysts were damaged, in comparison with the initial population. The efficiency increased with the number of the hydrodynamic cavitation cycles, or in combination with a separation technique for cysts. There was also a significant decrease in bacterial abundance and growth rate, compared to the initial number and growth potential. PMID- 26902684 TI - Localised and limited impact of a dredging operation on coral cover in the northwestern lagoon of New Caledonia. AB - We report here an interannual survey (2006-2012) of coral cover in the northwestern lagoon of New Caledonia, to assess the impact of an important dredging operation (August 2008-February 2010) associated with the construction of the largest nickel mining site in the Pacific. A BACI (Before-After Control Impact) analysis failed to detect any significant interaction between period (before, during, and after dredging) and the category of the stations (impact vs. control). Among the 31 stations surveyed, only seven showed decreasing coral cover during the study period, mainly due to a decline in Acroporidae. However, the relationship between the dredging and this decrease was highly plausible only for one station, situated 0.9km from the dredging site. High hydrodynamism in the study area, the abundance of resistant corals and efficient protective measures during the dredging operation might explain these localised and limited impacts. PMID- 26902685 TI - Potential biodegradation of crude petroleum oil by newly isolated halotolerant microbial strains from polluted Red Sea area. AB - Two microbial isolates from oil polluted Red Sea water in Egypt, designated as RS Y1 and RS-F3, were found capable of degrading Belayim mix (BX) crude oil. Strains RS-Y1 and RS-F3 were assigned to the genera Lipomyces tetrasporus and Paecilomyces variotii based on their morphological and physiological characteristics. Both isolates were compared for the biodegradation of crude petroleum-oil hydrocarbons in basal salt medium supplemented with 5% (w/v) of BX crude oil. Gas chromatography profile showed that the biodegradation of total petroleum hydrocarbons (TPHs) inoculated with L. tetrasporus (68.3%) and P. variotii (58.15%) along with their consortium (66%) significantly reduced TPHs levels as compared to the control after 30days. L. tetrasporus (44.5%) was more effective than P. variotii strain (32.89%) in reducing the unresolved complex mixtures (UCM) content from the medium. Both isolates exhibited a strong growth over a wide range of salinity (5-45g/L NaCl). PMID- 26902686 TI - The effect of sewage pollution on the feeding behaviour and diet of Hediste (Nereis diversicolor (O.F. Muller, 1776)) in three estuaries in south-east England, with implications for saltmarsh erosion. AB - Stable isotope analyses of the abundant infaunal polychaete Hediste diversicolor, recognised as an indicator of sewage pollution, support the hypothesis that nutrient enrichment promotes surface deposit feeding, over suspension feeding and predation. At sewage-polluted sites in three estuaries in SE England Hediste mainly consumed microphytobenthos, sediment organic matter and filamentous macroalgae Ulva spp. At cleaner sites Hediste relied more on suspension feeding and consumption of Spartina anglica. There were no consistent differences in Hediste densities between the polluted and cleaner sites, probably because of increased densities at the cleaner sites too, facilitated by the planting of Spartina and nitrogen enrichment there too, including from agricultural run-off. Increased nutrient enrichment and the artificial availability of Spartina have probably increased densities of, and deposit-feeding by, Hediste in the past half century and contributed indirectly to saltmarsh losses, since deposit-feeding by Hediste has been implicated in recent saltmarsh erosion in SE England. PMID- 26902687 TI - Bioavailability and assessment of heavy metal pollution in sediment cores off the Mejerda River Delta (Gulf of Tunis): How useful is a multiproxy approach? AB - Three core samples were taken from zones offshore from the Mejerda River Delta (Tunisia) and analyzed for major and trace elements to assess their relationships with organic matter, monosulfides and carbonates, as well as for pollution and bioavailability. Chemical speciation, ? SEM/AVS, the enrichment factor (EF) and the geo-accumulation index (I-geo) were used. Iron, cadmium, lead and zinc - the most frequently mined metals in the Mejerda catchment - were found as contaminants in the offshore areas. Estimations of trace element accumulation using the EF and the I-geo index show that lead, and to a lesser extent zinc, are the most polluting metals off the Mejerda outlet. According to their bioavailability, these metals are also the most toxic. Only cadmium is heavily present in delta sediment (EF>100) though deeply sequestrated (100% bound to the residual fraction) and thus presents no toxicity. PMID- 26902688 TI - The membrane as the gatekeeper of infection: Cholesterol in host-pathogen interaction. AB - The cellular plasma membrane serves as a portal for the entry of intracellular pathogens. An essential step for an intracellular pathogen to gain entry into a host cell therefore is to be able to cross the cell membrane. In this review, we highlight the role of host membrane cholesterol in regulating the entry of intracellular pathogens using insights obtained from work on the interaction of Leishmania and Mycobacterium with host cells. The entry of these pathogens is known to be dependent on host membrane cholesterol. Importantly, pathogen entry is inhibited either upon depletion (or complexation), or enrichment of membrane cholesterol. In other words, an optimum level of host membrane cholesterol is necessary for efficient infection by pathogens. In this overall context, we propose a general mechanism, based on cholesterol-induced conformational changes, involving cholesterol binding sites in host cell surface receptors that are implicated in this process. A therapeutic strategy targeting modulation of membrane cholesterol would have the advantage of avoiding the commonly encountered problem of drug resistance in tackling infection by intracellular pathogens. Insights into the role of host membrane cholesterol in pathogen entry would be instrumental in the development of novel therapeutic strategies to effectively tackle intracellular pathogenesis. PMID- 26902689 TI - Efficiency of two nitrification inhibitors (dicyandiamide and 3, 4 dimethypyrazole phosphate) on soil nitrogen transformations and plant productivity: a meta-analysis. AB - Dicyandiamide (DCD) and 3, 4-dimethypyrazole phosphate (DMPP) are often claimed to be efficient in regulating soil N transformations and influencing plant productivity, but the difference of their performances across field sites is less clear. Here we applied a meta-analysis approach to compare effectiveness of DCD and DMPP across field trials. Our results showed that DCD and DMPP were equally effective in altering soil inorganic N content, dissolve inorganic N (DIN) leaching and nitrous oxide (N2O) emissions. DCD was more effective than DMPP on increasing plant productivity. An increase of crop yield by DMPP was generally only observed in alkaline soil. The cost and benefit analysis (CBA) showed that applying fertilizer N with DCD produced additional revenues of $109.49 ha(-1) yr( 1) for maize farms, equivalent to 6.02% increase in grain revenues. In comparisons, DMPP application produced less monetary benefit of $15.67 ha(-1) yr( 1). Our findings showed that DCD had an advantage of bringing more net monetary benefit over DMPP. But this may be weakened by the higher toxicity of DCD than DMPP especially after continuous DCD application. Alternatively, an option related to net monetary benefit may be achieved through applying DMPP in alkaline soil and reducing the cost of purchasing DMPP products. PMID- 26902690 TI - In situ-immobilization of two model cyanobacterial strains in ceramic structures: A new biohybrid material for photobioreactor applications. AB - Two cyanobacterial strains, Synechocystis sp. PCC 6803 and Nostoc punctiforme ATCC 29133 were immobilized within magnesium phosphate based cements, showing a viability and activity for at least 4 weeks. These biohybrids are considered as an alternative photobioreactor material for bioremediation or an improved yield of biotechnologically relevant molecules. PMID- 26902692 TI - Composition of fecal microbiota of laboratory mice derived from Japanese commercial breeders using 16S rRNA gene clone libraries. AB - The fecal microbiota of six mice derived from three Japanese commercial breeders was analyzed by using 16S rRNA gene clone libraries to construct a database for analyzing the gut microbiota of laboratory mice. The 566 clones were obtained from the clone libraries generated from the fecal DNA samples derived from BALB/c, C57BL/6N, DBA/2 and ICR mice. Among these 566 clones, there were 446 unique 16S rRNA gene sequences. When grouped at the 98% similarity level, the 446 unique sequences consisted of 103 Clostridiales, 43 Bacteroidales, 5 Lactobacillus and 3 Erysipelotricaceae, as well as sequences from 11 other phyla. PMID- 26902691 TI - Metformin may protect nondiabetic breast cancer women from metastasis. AB - Metformin, a widely prescribed oral hypoglycemic agent, has recently received a big interest because of its potential antitumorigenic effects in different cancer types. The present study investigated the impact of adding metformin to breast cancer adjuvant therapy in nondiabetic women on, insulin like growth factor-1 (IGF-1), IGF binding protein-3 (IGFBP-3), insulin, fasting blood glucose (FBG), the molar ratio of IGF-1 to IGFBP-3, homeostatic model assessment of insulin resistance (HOMA-IR) and metastasis. 102 women with newly diagnosed breast cancer were divided into 2 main groups, a control group and a metformin group. All women were treated with adjuvant therapy, according to the protocols of Ministry of Health and Population and National Cancer Institute, Egypt. Moreover, the women in the metformin group received 850 mg of metformin twice daily. Blood samples were collected at baseline, after chemotherapy (CT), after 6 months of hormonal therapy (6-HT) and 12 months of hormonal therapy (12-HT) for analysis of serum IGF-1, IGFBP-3, insulin, FBG and cancer antigen 15-3 (CA15-3). Metformin resulted in a significant reduction of IGF-1, IGF-1: IGFBP-3 molar ratio, insulin, FBG and HOMA-IR. On the other hand, metformin caused a significant increase of IGFBP-3. Moreover, metformin significantly decreased the numbers of metastatic cases after 6-HT. Metformin may have potential antitumor and antimetastatic effects that need further clinical investigations. This may be attributed to either the significant increase of the apoptotic inducer IGFBP-3 or/and the significant reduction of mitogenic insulin, IGF-1, free bioactive IGF-1, FBG and HOMA-IR. PMID- 26902694 TI - An unusual thoracic spinal pathology presenting as a dorsally exophytic intramedullary lesion. PMID- 26902693 TI - Anti-NDV activity of baicalin from a traditional Chinese medicine in vitro. AB - The purpose of this study was to investigate the anti-Newcastle disease virus (NDV) activities of baicalin from Scutellaria baicalensis, a Traditional Chinese Medicine in vitro. Chicken embryo fibroblasts (CEFs) were infected with NDV, and quantitative analysis of apoptotic cells was performed using flow cytometry. Cytotoxicity and anti-viral activities of baicalin were studied using the MTT method. The results showed that the maximal safe concentrations of baicalin to CEFs was 1 * 2(-2) mg/ml. Baicalin could directly kill NDV, inhibit the infectivity of NDV to CEF and block intracellular NDV. It inhibited the apoptosis of NDV-infected CEFs and suppressed the spread of NDV. These results indicate that baicalin has strong anti-NDV activity and has the potential for use as components of an antiviral drug. PMID- 26902695 TI - Atlas fractures with a Dickman's type I transverse ligament injury. PMID- 26902696 TI - Rapid resolution of large spontaneous thoracic epidural hematoma without surgical intervention. PMID- 26902697 TI - An extremely rare case of low-grade glioma of the conus medullaris in children. PMID- 26902698 TI - Reply to 'Lack of replication of association of THSD7A with obesity'. PMID- 26902699 TI - Lack of replication of association of THSD7A with obesity. PMID- 26902700 TI - Assessment of the Effects of Tribulus Terrestris on Sexual Function of Menopausal Women. AB - OBJECTIVE: The aim of this study was to study the effects of Tribulus terrestris on sexual function in menopausal women. METHODS: This was a prospective, randomized, double-blind, placebo-controlled clinical trial that included 60 postmenopausal women with sexual dysfunction. The women were divided into two groups, placebo group and Tribulus group, and evaluated by using the Sexual Quotient-female version (SQ-F) and Female Intervention Efficacy Index (FIEI) questionnaires. RESULTS: There was no significant difference between the groups in age, age at menopause, civil status, race, and religion. In the evaluation with the SQ-F questionnaire, there were significant differences between the placebo (7.6 +/- 3.2) and Tribulus (10.2 +/- 3.2) groups in the domains of desire and sexual interest (p <= 0.001), foreplay (3.3 +/- 1.5 versus 4.2 +/- 1.0) (p <= 0.01), arousal and harmonious interaction with the partner (5.7 +/- 2.1 versus 7.2 +/- 2.6) (p <= 0.01), and comfort in sexual intercourse (6.5 +/- 2.4 versus 8.0 +/- 1.9) (p <= 0.01). There was no significant difference between the placebo and Tribulus groups in the domains of orgasm and sexual satisfaction (p = 0.28). In the FIEI questionnaire, there was a significant improvement (p < 0.001) in the domains of vaginal lubrication during coitus and/or foreplay (20 versus 83.3%), sensation in the genitalia during sexual intercourse or other stimuli (16.7 versus 76.7%), sensation in the genital region (20 versus 70%), sexual intercourse and/or other sexual stimulations (13.3 versus 43.3%), and the ability to reach orgasm (20% versus 73.3%). There was no significant difference in adverse effects between the two groups. CONCLUSIONS: After 90 days of treatment, at the doses used, we found Tribulus terrestris to be effective in treating sexual problems among menopausal women. PMID- 26902701 TI - Lack of data on standardized metrics for surgical care in a developing country with middle total expenditure on health. PMID- 26902702 TI - Regarding "Risk Factors for Immediate and Delayed-Onset Fever After Percutaneous Transhepatic Biliary Drainage". PMID- 26902703 TI - Radiofrequency Wire Recanalization of Chronically Thrombosed TIPS. AB - Radiofrequency (RF) guide wires have been applied to cardiac interventions, recanalization of central venous thromboses, and to cross biliary occlusions. Herein, the use of a RF wire technique to revise chronically occluded transjugular intrahepatic portosystemic shunts (TIPS) is described. In both cases, conventional TIPS revision techniques failed to revise the chronically thrombosed TIPS. RF wire recanalization was successfully performed through each of the chronically thrombosed TIPS, demonstrating initial safety and feasibility in this application. PMID- 26902704 TI - Endovascular Management of Intractable Postpartum Hemorrhage Caused by Vaginal Laceration. AB - PURPOSE: We evaluated the management of transcatheter arterial embolization for postpartum hemorrhage caused by vaginal laceration. MATERIALS AND METHODS: We reviewed seven cases of patients (mean age 30.9 years; range 27-35) with intractable hemorrhages and pelvic hematomas caused by vaginal lacerations, who underwent superselective transcatheter arterial embolization from January 2008 to July 2014. Postpartum hemorrhage was evaluated by angiographic vascular mapping to determine the vaginal artery's architecture, technical and clinical success rates, and complications. RESULTS: The vaginal artery was confirmed as the source of bleeding in all cases. The artery was found to originate from the uterine artery in three cases, the uterine and obturator arteries in two, or the internal pudendal artery in two. After vaginal artery embolization, persistent contrast extravasation from the inferior mesenteric artery as an anastomotic branch was noted in one patient. Nontarget vessels (the inferior vesical artery and nonbleeding vaginal arterial branches) were embolized in one patient. Effective control of hemostasis and no post-procedural complications were confirmed for all cases. CONCLUSION: Postpartum hemorrhages caused by vaginal lacerations involve the vaginal artery arising from the anterior trunk of the internal iliac artery with various branching patterns. Superselective vaginal artery embolization is clinically acceptable for the successful treatment of vaginal laceration hemorrhages, with no complications. After vaginal artery embolization, it is suggested to check for the presence of other possible bleeding vessels by pelvic aortography with a catheter tip at the L3 vertebral level, and to perform a follow-up assessment. PMID- 26902705 TI - Characterisation and expression analysis of two terminal complement components: C7 and C9 from large yellow croaker, Larimichthys crocea. AB - The large yellow croaker Larimichthys crocea, as one of the most economically important marine fish in China and East Asian countries, are facing the fatal attraction of various pathogens in recent years. Elucidation of the organism immunomodulatory mechanism of croaker response to pathogen infection is essential for the disease control. In present study, we reported for the first time the molecular characterization and expression analysis of two terminal complement components (TCCs) of croaker, Lc-C7 and Lc-C9. These two structural conserved TCCs were detected in many tissues in adult healthy fish, with highest levels detected in liver. The transcriptional expression analysis of Lc-C7 and Lc-C9 at different developmental stages showed a continuous increase towards hatch, however the two TCCs mRNA were not detected at the unfertilized stage, hinting the origination of these two TCCs after fertilization. Rapid and drastic responses to Vibrio alginolyticus challenge were observed for Lc-C7 and Lc-C9, suggesting the involvement of component C7 and C9 in innate immune responses to pathogenic invasion in teleost fish. These findings could deepen our understanding about immunomodulatory mechanisms of croaker and shed a new light to the role of component system in teleostean immunomodulation. PMID- 26902706 TI - Thiamin deficiency induces impaired fish gill immune responses, tight junction protein expression and antioxidant capacity: Roles of the NF-kappaB, TOR, p38 MAPK and Nrf2 signaling molecules. AB - In this study, we investigate the effects of dietary thiamin deficiency on immune responses, tight junctions, antioxidant capacity and related signaling molecules in the gills of young grass carp (Ctenopharyngodon idella). Fish were fed diets that contained 0.12-2.04 mg thiamin kg(-1) for 8 weeks. We found that dietary thiamin deficiency resulted in reduced complement 3 content, lysozyme and acid phosphatase activities, mRNA levels of hepcidin, liver-expressed antimicrobial peptides 2, transforming growth factor (TGF)-beta1, interleukin (IL)-10, inhibitor protein-kappaBalpha (IkappaBalpha), ribosomal S6 protein kinase 1 and target of rapamycin (TOR) and increased expression of interferon-gamma2, tumor necrosis factor-alpha, TGF-beta2, IL-1beta, IL-8, IkappaB kinases (IKKbeta and IKKgamma) and nuclear factor-kappaB p65 (NF-kappaB p65). Our findings showed that thiamin deficiency reduced the immune status of fish gills. Furthermore, thiamin deficiency resulted in reduced mRNA transcript levels of claudin b, claudin 3, claudin 12, zonula occludens 1 (ZO-1) and occludin and increased mRNA transcript levels of claudin 15a, myosin light-chain kinase (MLCK) and p38 mitogen-activated protein kinase (p38 MAPK) in fish gill tissues. These data suggested that thiamin deficiency disrupted tight junction-mediated fish gill barrier function. Additionally, reactive oxygen species, malondialdehyde and protein carbonyl levels and both the activities and expression levels of Cu/Zn superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferases and glutathione reductase, as well as NF-E2-related factor 2 gene expression in fish gills, were lower in fish fed a thiamin-deficient diet. By contrast, thiamin deficiency increased levels of Kelch-like-ECH-associated protein 1a (Keap1a) and Keap1b mRNA transcript expression in fish gills. Taken together, our findings indicated that thiamin deficiency impaired fish gill health by effects on the expression of genes encoding cytokines, tight junction proteins, antioxidant enzymes, NF-kappaB p65, MLCK and Nrf2. PMID- 26902707 TI - Evaluating the Small-World-Ness of a Sampled Network: Functional Connectivity of Entorhinal-Hippocampal Circuitry. AB - The amount of publicly accessible experimental data has gradually increased in recent years, which makes it possible to reconsider many longstanding questions in neuroscience. In this paper, an efficient framework is presented for reconstructing functional connectivity using experimental spike-train data. A modified generalized linear model (GLM) with L1-norm penalty was used to investigate 10 datasets. These datasets contain spike-train data collected from the entorhinal-hippocampal region in the brains of rats performing different tasks. The analysis shows that entorhinal-hippocampal network of well-trained rats demonstrated significant small-world features. It is found that the connectivity structure generated by distance-dependent models is responsible for the observed small-world features of the reconstructed networks. The models are utilized to simulate a subset of units recorded from a large biological neural network using multiple electrodes. Two metrics for quantifying the small-world ness both suggest that the reconstructed network from the sampled nodes estimates a more prominent small-world-ness feature than that of the original unknown network when the number of recorded neurons is small. Finally, this study shows that it is feasible to adjust the estimated small-world-ness results based on the number of neurons recorded to provide a more accurate reference of the network property. PMID- 26902708 TI - In Reply. PMID- 26902709 TI - Traumatic Dysgeusia, an Unusual Complication of Facial Trauma: A Case Report. AB - The chemical senses of taste and smell are important to human life, because they play an important role in detecting potential environmental hazards. Humans can identify countless different flavors by the simultaneous perception of taste and smell. Reports of sensory loss after craniocerebral trauma began to appear in the medical literature in the middle 1800s. Dysgeusia associated with head injuries is rare and its reported incidence is 0.4 to 0.5%. This report describes the clinical case of a 32-year-old man with Le Fort I and III fractures treated with surgical reduction and fixation. The patient presented with dysgeusia after slight improvement of his preoperative anosmia. The prognosis is favorable and the treatment is prospective. PMID- 26902710 TI - Use of Botox (OnabotulinumtoxinA) for the Treatment of Parotid Sialocele and Fistula After Extirpation of Buccal Squamous Cell Carcinoma With Immediate Reconstruction Using Microvascular Free Flap: A Report of 3 Cases. AB - PURPOSE: Buccal squamous cell carcinoma is an aggressive form of oral carcinoma with a high recurrence rate. Injury to the parotid duct is often unavoidable when surgically treating buccal squamous cell carcinoma because of the intimate anatomic relation among the buccal mucosa, Stensen duct, and parotid gland. It is often difficult to achieve negative margins and preserve the integrity of the parotid duct. Sialocele formation is a frequent and untoward complication owing to extravasation of saliva into the surgical defect, which delays healing, creates fistulas, and produces painful facial swelling. Currently, no consensus exists regarding the management of a parotid sialocele. Multiple investigators have described different modalities of treatment, such as repeated percutaneous needle aspiration, pressure dressings, antisialagogue therapy, radiotherapy, botulinum toxin, and surgical techniques, including duct repair, diversion, ligation, drain placement, and parotidectomy. MATERIALS AND METHODS: With approval from the institutional review board of the University of Texas Health Sciences Center at Houston, 3 cases of parotid sialocele and nonhealing fistulas successfully treated with Botox (onabotulinumtoxinA) after tumor extirpation, neck dissection, and reconstruction with a microvascular free flap are presented. RESULTS: At the University of Texas Health Sciences Center at Houston, the radiation oncologist prefers not to start adjunctive radiation treatment with a nonhealing wound or a drain in the field of radiation. Ideally, a standard timing of adjuvant radiotherapy is 6 to 8 weeks after surgery and 60 cGy should be completed before 7 months. CONCLUSIONS: With the use of Botox, the nonhealing wound resolved and the drain was removed at least 2 weeks before the initiation of adjunctive radiotherapy, thus minimizing the delay in adjuvant treatment. PMID- 26902711 TI - Periarticular Cysts of the Temporomandibular Joint Are More Frequently Synovial Than Ganglion. AB - PURPOSE: Differentiating between ganglion and synovial cysts by standard histology is difficult, leading to inaccurate statements on frequency for each of these periarticular lesions. The purpose of this study was to use immunohistochemical (IHC) analysis to 1) calculate the accuracy of the histologic diagnoses, 2) determine the frequency of ganglion and synovial cysts of the temporomandibular joint (TMJ), and 3) compare the frequency of these lesions in the TMJ compared with the extracranial skeleton in patients treated at Massachusetts General Hospital (MGH). MATERIALS AND METHODS: This is a retrospective cohort study of all patients undergoing treatment of TMJ cysts at MGH from 2001 through 2013. IHC analysis of tissue samples for each patient was completed and compared with the original histologic diagnoses. Categorical variables, including age, gender, and sidedness, were recorded. A natural language search of the MGH Department of Pathology database determined the frequency of extracranial periarticular cysts during the same period. RESULTS: Thirteen patients met the inclusion criteria. Eleven cysts were synovial and 2 were ganglion based on histology. IHC analysis identified 2 false-positive synovial cyst diagnoses, resulting in 100% sensitivity and 50% specificity for the original histologic assessment and a percentage error of 22%. Of the periarticular TMJ lesions, 69% were synovial cysts and 31% were ganglion cysts. The frequency of TMJ versus extracranial ganglion cysts was 0.24%, and the frequency of TMJ versus extracranial synovial cysts was 0.60% based on 3,176 extracranial cysts (1,506 synovial; 1,670 ganglion). CONCLUSION: This study represents the largest single-institution experience with periarticular cysts of the TMJ, and contrary to previous reports, TMJ cysts appear to be more frequently synovial than ganglion. IHC can be used to overcome the relatively poor specificity of histologic diagnosis of synovial cysts. PMID- 26902712 TI - Descending necrotizing mediastinitis as a complication of odontogenic infection. AB - Descending necrotizing mediastinitis (DNM) is a serious, life threatening complication that can occur from a common odontogenic infection. Even with advancements in antibiotics, diagnostic imaging, and surgical management, the mortality rate remains between 20 and 40%. It is imperative that the practitioner taking care of patients with odontogenic infections be sensitized to this potentially fatal complication. We report the successful management of a case of mediastinitis complicating an odontogenic infection in a 39-year-old male. PMID- 26902713 TI - Colocutaneous fistula complicating sigmoid diverticulitis. AB - Colocutaneous fistula is a very rare complication of colonic diverticular disease. Herein we describe a case with a fistula connecting the sigmoid with the left flank area complicating diverticulitis of the sigmoid colon. An 85-year-old female patient with a history of acute diverticulitis 3 months earlier, was admitted with a subcutaneous abscess in the left flank. The abscess was drained and subsequently a colocutaneous fistula was established. At operation the sigmoid colon with the fistulous tract were excised. The patient had no postoperative complications and at present, 2 years later, she fares well. Colocutaneous fistula is a serious complication of chronic diverticulitis and requires surgical excision for its definite treatment. PMID- 26902714 TI - Combined medical, surgical and endovascular treatment of a giant cell arteritis case manifesting as upper limbs acute ischemia. AB - We report a case of giant cell arteritis manifesting as upper limbs ischemia due to a complete occlusion of the left subclavian artery and a high grade stenosis of the right subclavian artery. We decided to use a combined medical, surgical and endovascular treatment followed by long term treatment with methotrexate. After 4years the patient had no signs or symptoms of relapse. In our personal experience long term treatment with Methotrexate demonstrated a certain efficacy in avoiding relapse of the inflammatory phase and in maintaining stability of results in this kind of disease. PMID- 26902715 TI - Transcription Profiling of NOD-like Receptors in the Human Cornea with Disease. AB - PURPOSE: To investigate the expression of nucleotide-binding oligomerization domain-like receptors (NLRs) in human corneas with disease and corneal cells. METHODS: The expression of NOD1, NOD2, NLRP1, and NLRP3 was analyzed using real time RT-PCR in (1) corneas with active infection, history of herpetic stromal keratitis (HSK), chronic allograft rejection, and limbal stem cell deficiency (LSCD), and (2) human corneal cells after lipopolysaccharide (LPS) stimulation. Healthy corneas and cells without LPS served as controls. RESULTS: The mRNA levels of NOD2 and NLRP3 were increased in corneas with infection and HSK. Conversely, the levels of NOD1, NOD2, NLRP1, and NLRP3 transcripts were decreased in corneas with LSCD. In corneas with rejection, the expression of NOD1 and NLRP1 was downregulated. Corneal endothelial cells upregulated the expression of NOD2 and NLRP3 upon LPS. CONCLUSIONS: The changes in the NLR expression may reflect different susceptibility to infectious and non-infectious injuries in corneas with various diseases. PMID- 26902716 TI - Aharonov-Bohm oscillations in Dirac semimetal Cd3As2 nanowires. AB - Three-dimensional Dirac semimetals, three-dimensional analogues of graphene, are unusual quantum materials with massless Dirac fermions, which can be further converted to Weyl fermions by breaking time reversal or inversion symmetry. Topological surface states with Fermi arcs are predicted on the surface and have been observed by angle-resolved photoemission spectroscopy experiments. Although the exotic transport properties of the bulk Dirac cones have been demonstrated, it is still a challenge to reveal the surface states via transport measurements due to the highly conductive bulk states. Here, we show Aharonov-Bohm oscillations in individual single-crystal Cd3As2 nanowires with low carrier concentration and large surface-to-volume ratio, providing transport evidence of the surface state in three-dimensional Dirac semimetals. Moreover, the quantum transport can be modulated by tuning the Fermi level using a gate voltage, enabling a deeper understanding of the rich physics residing in Dirac semimetals. PMID- 26902717 TI - Design and development of a modified runway model of mouse drug self administration. AB - The present study established a novel mouse model of a runway drug self administration in our laboratory. The operant runway apparatus consisted of three long runways arranged in a zig-zag manner. The methodology consisted of six distinct phases: habituation, preconditioning, conditioning, post-conditioning, extinction and reinstatement. The effects of saline were compared with escalating doses of either ethanol (0.5-4.0 g/kg, i.p), heroin (5-40 mg/kg, i.p), or nicotine (0.1-0.5mg/kg, i.p) administered in the goal box during the conditioning phase (day 1 to day 5). A significant decrease in the time of trained (conditioned) mice to reach the goal box confirmed the subjects' motivation to seek those drugs on day 6 (expression). The mice were then subjected to non rewarded extinction trials for 5 days over which run times were significantly increased. After 5 days of abstinence, a priming dose of ethanol or heroin (1/5th of maximum dose used in conditioning) significantly reinstated the drug-seeking behavior. These results suggest that the modified runway model can serve as a powerful behavioral tool for the study of the behavioral and neurobiological bases of drug self-administration and, as such, is appropriate simple but powerful tool for investigating the drug-seeking behavior of laboratory mice. PMID- 26902718 TI - The light side of the force. AB - A combination of two single-molecule techniques has revealed new tertiary interactions in the TPP riboswitch. PMID- 26902719 TI - Adapt or avoid. AB - An enzyme called p38 MAP kinase helps nematodes to adapt to low-oxygen environments, and also to escape from them. PMID- 26902720 TI - Active and water-soluble form of lipidated Wnt protein is maintained by a serum glycoprotein afamin/alpha-albumin. AB - Wnt plays important role during development and in various diseases. Because Wnts are lipidated and highly hydrophobic, they can only be purified in the presence of detergents, limiting their use in various in vitro and in vivo assays. We purified N-terminally tagged recombinant Wnt3a secreted from cells and accidentally discovered that Wnt3a co-purified with a glycoprotein afamin derived from the bovine serum included in the media. Wnt3a forms a 1:1 complex with afamin, which remains soluble in aqueous buffer after isolation, and can induce signaling in various cellular systems including the intestical stem cell growth assay. By co-expressing with afamin, biologically active afamin-Wnt complex can be easily obtained in large quantity. As afamin can also solubilize Wnt5a, Wnt3, and many more Wnt subtypes, afamin complexation will open a way to put various Wnt ligands and their signaling mechanisms under a thorough biochemical scrutiny that had been difficult for years. PMID- 26902721 TI - Evolution of the microstructure during the process of consolidation and bonding in soft granular solids. AB - The evolution of microstructure during powder compaction process was investigated using a discrete particle modeling, which accounts for particle size distribution and material properties, such as plasticity, elasticity, and inter-particle bonding. The material properties were calibrated based on powder compaction experiments and validated based on tensile strength test experiments for lactose monohydrate and microcrystalline cellulose, which are commonly used excipient in pharmaceutical industry. The probability distribution function and the orientation of contact forces were used to study the evolution of the microstructure during the application of compaction pressure, unloading, and ejection of the compact from the die. The probability distribution function reveals that the compression contact forces increase as the compaction force increases (or the relative density increases), while the maximum value of the tensile contact forces remains the same. During unloading of the compaction pressure, the distribution approaches a normal distribution with a mean value of zero. As the contact forces evolve, the anisotropy of the powder bed also changes. Particularly, during loading, the compression contact forces are aligned along the direction of the compaction pressure, whereas the tensile contact forces are oriented perpendicular to direction of the compaction pressure. After ejection, the contact forces become isotropic. PMID- 26902723 TI - Small is beautiful: Surprising nanoparticles. AB - In the preparation of nanoparticles for drug delivery, it is well known that their size as well as their surface decorations can play a major role in interaction with living media. It is less known that their shape and internal structure can interplay with cellular and in vivo fate. The scientific literature is full of a large variety of surprising terms referring to their shape and structure. The aim of this review is to present some examples of the most often encountered surprising nanoparticles prepared and usable in the pharmaceutical technology domain. They are presented in two main groups related to their physical aspects: 1) smooth surface particles, such as Janus particles, "snowmen", "dumbbells", "rattles", and "onions" and 2) branched particles, such as "flowers", "stars" and "urchins". The mode of preparation and potential applications are briefly presented. The topic has a serious, wider importance, namely in opportunity these structures have to allow exploration of the role of shape and structure on the utility (and perhaps toxicity) of these nanostructures. PMID- 26902722 TI - Enhanced pulmonary delivery of fluticasone propionate in rodents by mucus penetrating nanoparticles. AB - Most attempts to achieve sustained drug delivery to pulmonary tissues using nanoparticles have focused on mucoadhesive particles (MAP). However, MAP become trapped in the luminal mucus layer and, as a result, are largely eliminated from the respiratory tract by mucociliary escalator and expiratory clearance, which undermines their sustained release potential. Recent studies have shown that mucus-penetrating particles (MPP) engineered to diffuse through mucus can avoid rapid mucociliary clearance in vivo and persist in the lung longer. Nonetheless, it has not been confirmed that MPP encapsulating small molecules can sustain drug release in the lung longer than MAP of similar size and core composition. As a proof of concept, we encapsulated fluticasone propionate (FP) into poly(lactide) based MPP and MAP (both ~ 200 nm diameter, ~ 30-35% drug loading) and evaluated their pulmonary residence by measuring FP levels in mouse lungs over 24h following intratracheal instillation. Furthermore, we evaluated the duration of action of FP MPP in a rat lung inflammation model compared to that of a non encapsulated FP control. In rodents, pulmonary delivery of FP formulated as MPP provided a 60% higher local exposure compared to MAP and extended the single dose efficacy by at least 16 h compared to non-encapsulated FP. PMID- 26902724 TI - The Protease Locus of Francisella tularensis LVS Is Required for Stress Tolerance and Infection in the Mammalian Host. AB - Francisella tularensis is the causative agent of tularemia and a category A potential agent of bioterrorism, but the pathogenic mechanisms of F. tularensis are largely unknown. Our previous transposon mutagenesis screen identified 95 lung infectivity-associated F. tularensis genes, including those encoding the Lon and ClpP proteases. The present study validates the importance of Lon and ClpP in intramacrophage growth and infection of the mammalian host by using unmarked deletion mutants of the F. tularensis live vaccine strain (LVS). Further experiments revealed that lon and clpP are also required for F. tularensis tolerance to stressful conditions. A quantitative proteomic comparison between heat-stressed LVS and the isogenic Lon-deficient mutant identified 29 putative Lon substrate proteins. The follow-up protein degradation experiments identified five substrates of the F. tularensis Lon protease (FTL578, FTL663, FTL1217, FTL1228, and FTL1957). FTL578 (ornithine cyclodeaminase), FTL663 (heat shock protein), and FTL1228 (iron-sulfur activator complex subunit SufD) have been previously described as virulence-associated factors in F. tularensis Identification of these Lon substrates has thus provided important clues for further understanding of the F. tularensis stress response and pathogenesis. The high-throughput approach developed in this study can be used for systematic identification of the Lon substrates in other prokaryotic and eukaryotic organisms. PMID- 26902725 TI - Development of an Ex Vivo Tissue Platform To Study the Human Lung Response to Coxiella burnetii. AB - Coxiella burnetii is an intracellular bacterial pathogen that causes human Q fever, an acute debilitating flu-like illness that can also present as chronic endocarditis. Disease typically occurs following inhalation of contaminated aerosols, resulting in an initial pulmonary infection. In human cells, C. burnetii generates a replication niche termed the parasitophorous vacuole (PV) by directing fusion with autophagosomes and lysosomes. C. burnetii requires this lysosomal environment for replication and uses a Dot/Icm type IV secretion system to generate the large PV. However, we do not understand how C. burnetii evades the intracellular immune surveillance that triggers an inflammatory response. We recently characterized human alveolar macrophage (hAM) infection in vitro and found that avirulent C. burnetii triggers sustained interleukin-1beta (IL-1beta) production. Here, we evaluated infection of ex vivo human lung tissue, defining a valuable approach for characterizing C. burnetii interactions with a human host. Within whole lung tissue, C. burnetii preferentially replicated in hAMs. Additionally, IL-1beta production correlated with formation of an apoptosis associated speck-like protein containing a caspase activation and recruitment domain (ASC)-dependent inflammasome in response to infection. We also assessed potential activation of a human-specific noncanonical inflammasome and found that caspase-4 and caspase-5 are processed during infection. Interestingly, although inflammasome activation is closely linked to pyroptosis, lytic cell death did not occur following C. burnetii-triggered inflammasome activation, indicating an atypical response after intracellular detection. Together, these studies provide a novel platform for studying the human innate immune response to C. burnetii. PMID- 26902726 TI - Pseudomonas aeruginosa and Its Bacterial Components Influence the Cytokine Response in Thymocytes and Splenocytes. AB - Infections with Pseudomonas aeruginosa may cause many different diseases. The spectrum of such infections in general includes inflammation and bacterial sepsis. Hospital-acquired pneumonia, naturally resistant to a wide range of antibiotics, is associated with a particularly high mortality rate in mechanically ventilated patients. The pathogenesis of P. aeruginosa is complex and mediated by several virulence factors, as well as cell-associated factors. We have previously demonstrated that stimulation with different bacteria triggers the cytokine response of thymocytes. In this study, we investigated the effect of P. aeruginosa and its different components on the cytokine production of immature and mature immune cells. We found that the induced cytokine pattern in the thymus and the spleen after infections with P. aeruginosa is primarily mediated by lipopolysaccharide (LPS) of the outer cell membrane, but other components of the bacterium can influence the cytokine secretion as well. Stimulation with heat killed P. aeruginosa and LPS does not influence the amount of cytokine-producing CD4(+) T cells but instead suppresses the emergence of Th17 cells. However, stimulation with P. aeruginosa or its components triggers the interleukin-17 (IL 17) response both in thymocytes and in splenocytes. We conclude that infections with P. aeruginosa affect the cytokine secretion of immature and mature cells and that IL-17 and Th17 cells play only a minor role in the development of pathological systemic inflammatory disease conditions during P. aeruginosa infections. Therefore, other inflammatory immune responses must be responsible for septic reactions of the host. PMID- 26902727 TI - Linocin and OmpW Are Involved in Attachment of the Cystic Fibrosis-Associated Pathogen Burkholderia cepacia Complex to Lung Epithelial Cells and Protect Mice against Infection. AB - Members of the Burkholderia cepacia complex (Bcc) cause chronic opportunistic lung infections in people with cystic fibrosis (CF), resulting in a gradual lung function decline and, ultimately, patient death. The Bcc is a complex of 20 species and is rarely eradicated once a patient is colonized; therefore, vaccination may represent a better therapeutic option. We developed a new proteomics approach to identify bacterial proteins that are involved in the attachment of Bcc bacteria to lung epithelial cells. Fourteen proteins were reproducibly identified by two-dimensional gel electrophoresis from four Bcc strains representative of two Bcc species: Burkholderia cenocepacia, the most virulent, and B. multivorans, the most frequently acquired. Seven proteins were identified in both species, but only two were common to all four strains, linocin and OmpW. Both proteins were selected based on previously reported data on these proteins in other species. Escherichia coli strains expressing recombinant linocin and OmpW showed enhanced attachment (4.2- and 3.9-fold) to lung cells compared to the control, confirming that both proteins are involved in host cell attachment. Immunoproteomic analysis using serum from Bcc-colonized CF patients confirmed that both proteins elicit potent humoral responses in vivo Mice immunized with either recombinant linocin or OmpW were protected from B. cenocepacia and B. multivorans challenge. Both antigens induced potent antigen specific antibody responses and stimulated strong cytokine responses. In conclusion, our approach identified adhesins that induced excellent protection against two Bcc species and are promising vaccine candidates for a multisubunit vaccine. Furthermore, this study highlights the potential of our proteomics approach to identify potent antigens against other difficult pathogens. PMID- 26902728 TI - Profoundly Reduced CD1c+ Myeloid Dendritic Cell HLA-DR and CD86 Expression and Increased Tumor Necrosis Factor Production in Experimental Human Blood-Stage Malaria Infection. AB - Dendritic cells (DCs) are sentinels of the immune system that uniquely prime naive cells and initiate adaptive immune responses. CD1c (BDCA-1) myeloid DCs (CD1c(+) mDCs) highly express HLA-DR, have a broad Toll-like receptor (TLR) repertoire, and secrete immune modulatory cytokines. To better understand immune responses to malaria, CD1c(+) mDC maturation and cytokine production were examined in healthy volunteers before and after experimental intravenous Plasmodium falciparum infection with 150- or 1,800-parasite-infected red blood cells (pRBCs). After either dose, CD1c(+) mDCs significantly reduced HLA-DR expression in prepatent infections. Circulating CD1c(+) mDCs did not upregulate HLA-DR after pRBC or TLR ligand stimulation and exhibited reduced CD86 expression. At peak parasitemia, CD1c(+) mDCs produced significantly more tumor necrosis factor (TNF), whereas interleukin-12 (IL-12) production was unchanged. Interestingly, only the 1,800-pRBC dose caused a reduction in the circulating CD1c(+) mDC count with evidence of apoptosis. The 1,800-pRBC dose produced no change in T cell IFN-gamma or IL-2 production at peak parasitemia or at 3 weeks posttreatment. Overall, CD1c(+) mDCs are compromised by P. falciparum exposure, with impaired HLA-DR and CD86 expression, and have an increased capacity for TNF but not IL-12 production. A first prepatent P. falciparum infection is sufficient to modulate CD1c(+) mDC responsiveness, likely contributing to hampered effector T cell cytokine responses and assisting parasite immune evasion. PMID- 26902729 TI - Imagining circles--Empirical data and a perceptual model for the arc-size illusion. AB - An essential part of visual object recognition is the evaluation of the curvature of both an object's outline as well as the contours on its surface. We studied a striking illusion of visual curvature--the arc-size illusion (ASI)--to gain insight into the visual coding of curvature. In the ASI, short arcs are perceived as flatter (less curved) compared to longer arcs of the same radius. We investigated if and how the ASI depends on (i) the physical size of the stimulus and (ii) on the length of the arc. Our results show that perceived curvature monotonically increases with arc length up to an arc angle of about 60 degrees , thereafter remaining constant and equal to the perceived curvature of a full circle. We investigated if the misjudgment of curvature in the ASI translates into predictable biases for three other perceptual tasks: (i) judging the position of the centre of circular arcs; (ii) judging if two circular arcs fall on the circumference of the same (invisible) circle and (iii) interpolating the position of a point on the circumference of a circle defined by two circular arcs. We found that the biases in all the above tasks were reliably predicted by the same bias mediating the ASI. We present a simple model, based on the central angle subtended by an arc, that captures the data for all tasks. Importantly, we argue that the ASI and related biases are a consequence of the fact that an object's curvature is perceived as constant with viewing distance, in other words is perceptually scale invariant. PMID- 26902730 TI - Conjectures regarding the nonlinear geometry of visual neurons. AB - From the earliest stages of sensory processing, neurons show inherent non linearities: the response to a complex stimulus is not a sum of the responses to a set of constituent basis stimuli. These non-linearities come in a number of forms and have been explained in terms of a number of functional goals. The family of spatial non-linearities have included interactions that occur both within and outside of the classical receptive field. They include, saturation, cross orientation inhibition, contrast normalization, end-stopping and a variety of non-classical effects. In addition, neurons show a number of facilitatory and invariance related effects such as those exhibited by complex cells (integration across position). Here, we describe an approach that attempts to explain many of the non-linearities under a single geometric framework. In line with Zetzsche and colleagues (e.g., Zetzsche et al., 1999) we propose that many of the principal non-linearities can be described by a geometry where the neural response space has a simple curvature. In this paper, we focus on the geometry that produces both increased selectivity (curving outward) and increased tolerance (curving inward). We demonstrate that overcomplete sparse coding with both low-dimensional synthetic data and high-dimensional natural scene data can result in curvature that is responsible for a variety of different known non-classical effects including end-stopping and gain control. We believe that this approach provides a more fundamental explanation of these non-linearities and does not require that one postulate a variety of explanations (e.g., that gain must be controlled or the ends of lines must be detected). In its standard form, sparse coding does not however, produce invariance/tolerance represented by inward curvature. We speculate on some of the requirements needed to produce such curvature. PMID- 26902731 TI - Rolling in the mud: Hippo controls oriented cell division. PMID- 26902732 TI - Fluorometric Detection of MicroRNA Using Isothermal Gene Amplification and Graphene Oxide. AB - We have developed a facile fluorometric system for the detection of microRNA (miRNA), using rolling circle amplification (RCA), graphene oxide (GO), and fluorescently labeled peptide nucleic acid (F-PNA). The padlock probe DNA complementary to a target miRNA was selectively ligated to form circular DNA that was then used as the template for RCA. F-PNAs complementary to the target miRNA were annealed to multiple sites of the isothermally amplified single-stranded RCA product (RCAP) containing multiple target miRNA sequences. This F-PNA/RCAP duplex is less adsorbed onto the GO monolayer, thus attenuating the quenching of F-PNA fluorescence by GO. In the absence of target miRNA (and hence the absence of RCA and duplex formation), the free F-PNA is completely adsorbed onto the GO monolayer and fluorescence quenching ensues. Thus, GO-based fluorescence detection coupled with isothermal gene amplification would be a simple and convenient method for the quantitative detection of miRNA. PMID- 26902734 TI - Shape manipulation of ion irradiated Ag nanoparticles embedded in lithium niobate. AB - Spherical silver nanoparticles were prepared by means of ion beam synthesis in lithium niobate. The embedded nanoparticles were then irradiated with energetic (84)Kr and (197)Au ions, resulting in different electronic energy losses between 8.1 and 27.5 keV nm(-1) in the top layer of the samples. Due to the high electronic energy losses of the irradiating ions, molten ion tracks are formed inside the lithium niobate in which the elongated Ag nanoparticles are formed. This process is strongly dependent on the initial particle size and leads to a broad aspect ratio distribution. Extinction spectra of the samples feature the extinction maximum with shoulders on either side. While the maximum is caused by numerous remaining spherical nanoparticles, the shoulders can be attributed to elongated particles. The latter could be verified by COMSOL simulations. The extinction spectra are thus a superposition of the spectra of all individual particles. PMID- 26902733 TI - On the use of 31P NMR for the quantification of hydrosoluble phosphorus containing compounds in coral host tissues and cultured zooxanthellae. AB - (31)P Nuclear Magnetic Resonance (NMR) was assessed to investigate the phosphorus containing compounds present in the tissues of the scleractinian coral Stylophora pistillata as well as of cultured zooxanthellae (CZ). Results showed that phosphorus-containing compounds observed in CZ were mainly phosphate and phosphate esters. Phosphate accounted for 19 +/- 2% of the total phosphorus compounds observed in CZ maintained under low P-levels (0.02 MUM). Adding 5 mM of dissolved inorganic phosphorus (KH2PO4) to the CZ culture medium led to a 3.1 fold increase in intracellular phosphate, while adding 5 mM of dissolved organic phosphorus led to a reduction in the concentration of phosphorus compounds, including a 2.5-fold intracellular phosphate decrease. In sharp contrast to zooxanthellae, the host mainly contained phosphonates, and to a lesser extent, phosphate esters and phosphate. Two-months of host starvation decreased the phosphate content by 2.4 fold, while bleaching of fed corals did not modify this content. Based on (31)P NMR analyses, this study highlights the importance of phosphonates in the composition of coral host tissues, and illustrates the impact of phosphorus availability on the phosphorus composition of host tissues and CZ, both through feeding of the host and inorganic phosphorus enrichment of the CZ. PMID- 26902735 TI - Bio-inspired stabilization of sulfenyl iodide RS-I in a Zr(IV)-based metal organic framework. AB - A Zr(IV)-based metal-organic framework (MOF) appended with free-standing thiol ( SH) groups was found to react readily with I2 molecules to form sulfenyl iodide (S-I) units. In contrast to its solution chemistry of facile disproportionation into disulfide and I2, the sulfenyl iodide (SI) function, anchored onto the rigid MOF grid and thus prevented from approaching one another to undergo the dismutation reaction, exhibits distinct stability even at elevated temperatures (e.g., 90 degrees C). On a conceptual plane, this simple and effective solid host also captures the spatial confinement observed for the complex biomacromolecular scaffolds involved in iodine thyroid chemistry, wherein the spatial isolation and consequent stabilization of sulfenyl/selenenyl iodides are exerted by means of the protein scaffolds. PMID- 26902736 TI - Exploring long-wave infrared transmitting materials with AxBy form: First principles gene-like studies. AB - Long-wave infrared (8-12 MUm) transmitting materials play critical roles in space science and electronic science. However, the paradox between their mechanical strength and infrared transmitting performance seriously prohibits their applications in harsh external environment. From the experimental view, searching a good window material compatible with both properties is a vast trail-and-error engineering project, which is not readily achieved efficiently. In this work, we propose a very simple and efficient method to explore potential infrared window materials with suitable mechanical property by first-principles gene-like searching. Two hundred and fifty-three potential materials are evaluated to find their bulk modulus (for mechanical performance) and phonon vibrational frequency (for optical performance). Seven new potential candidates are selected, namely TiSe, TiS, MgS, CdF2, HgF2, CdO, and SrO. Especially, the performances of TiS and CdF2 can be comparable to that of the most popular commercial ZnS at high temperature. Finally, we propose possible ranges of infrared transmission for halogen, chalcogen and nitrogen compounds respectively to guide further exploration. The present strategy to explore IR window materials can significantly speed up the new development progress. The same idea can be used for other material rapid searching towards special functions and applications. PMID- 26902737 TI - Effect of Health Literacy on Decision-Making Preferences among Medically Underserved Patients. AB - INTRODUCTION: Participation in the decision-making process and health literacy may both affect health outcomes; data on how these factors are related among diverse groups are limited. This study examined the relationship between health literacy and decision-making preferences in a medically underserved population. METHODS: We analyzed a sample of 576 primary care patients. Multivariable logistic regression was used to examine the independent association of health literacy (measured by the Rapid Estimate of Adult Literacy in Medicine-Revised) and patients' decision-making preferences (physician directed or patient involved), controlling for age, race/ethnicity, and gender. We tested whether having a regular doctor modified this association. RESULTS: Adequate health literacy (odds ratio [OR] = 1.7;P= 0.009) was significantly associated with preferring patient-involved decision making, controlling for age, race/ethnicity, and gender. Having a regular doctor did not modify this relationship. Males were significantly less likely to prefer patient-involved decision making (OR = 0.65;P= 0.024). DISCUSSION: Findings suggest health literacy affects decision making preferences in medically underserved patients. More research is needed on how factors, such as patient knowledge or confidence, may influence decision making preferences, particularly for those with limited health literacy. PMID- 26902740 TI - Funding uplift agreed under GP contract deal. PMID- 26902738 TI - Enhanced Boron Tolerance in Plants Mediated by Bidirectional Transport Through Plasma Membrane Intrinsic Proteins. AB - High boron (B) concentration is toxic to plants that limit plant productivity. Recent studies have shown the involvement of the members of major intrinsic protein (MIP) family in controlling B transport. Here, we have provided experimental evidences showing the bidirectional transport activity of rice OsPIP1;3 and OsPIP2;6. Boron transport ability of OsPIP1;3 and OsPIP2;6 were displayed in yeast HD9 mutant strain (?fps1?acr3?ycf1) as a result of increased B sensitivity, influx and accumulation by OsPIP1;3, and rapid efflux activity by OsPIP2;6. RT-PCR analysis showed strong upregulation of OsPIP1;3 and OsPIP2;6 transcripts in roots by B toxicity. Transgenic Arabidopsis lines overexpressing OsPIP1;3 and OsPIP2;6 exhibited enhanced tolerance to B toxicity. Furthermore, B concentration was significantly increased after 2 and 3 hours of tracer boron ((10)B) treatment. Interestingly, a rapid efflux of (10)B from the roots of the transgenic plants was observed within 1 h of (10)B treatment. Boron tolerance in OsPIP1;3 and OsPIP2;6 lines was inhibited by aquaporin inhibitors, silver nitrate and sodium azide. Our data proved that OsPIP1;3 and OsPIP2;6 are indeed involved in both influx and efflux of boron transport. Manipulation of these PIPs could be highly useful in improving B tolerance in crops grown in high B containing soils. PMID- 26902741 TI - Novel in situ multiharmonic EQCM-D approach to characterize complex carbon pore architectures for capacitive deionization of brackish water. AB - Multiharmonic analysis by electrochemical quartz-crystal microbalance with dissipation monitoring (EQCM-D) is introduced as an excellent tool for quantitative studying electrosorption of ions from aqueous solution in mesoporous (BP-880) or mixed micro-mesoporous (BP-2000) carbon electrodes. Finding the optimal conditions for gravimetric analysis of the ionic content in the charged carbon electrodes, we propose a novel approach to modeling the charge-dependent gravimetric characteristics by incorporation of Gouy-Chapman-Stern electric double layer model for ions electrosorption into meso- and micro-mesoporous carbon electrodes. All three parameters of the gravimetric equation evaluated by fitting it to the experimental mass changes curves were validated using supplementary nitrogen gas sorption analysis and complementing atomic force microscopy. Important overlap between gravimetric EQCM-D analysis of the ionic content of porous carbon electrodes and the classical capacitive deionization models has been established. The necessity and usefulness of non-gravimetric EQCM D characterizations of complex carbon architectures, providing insight into their unique viscoelastic behavior and porous structure changes, have been discussed in detail. PMID- 26902742 TI - Mindfulness and mindful eating: reflections on how individuals with cystic fibrosis may benefit. PMID- 26902743 TI - Adiponectin gene variants and abdominal obesity in an Iranian population. AB - INTRODUCTION: Waist-to-height ratio (WHtR) can be effective for the diagnosis of abdominal obesity and the risk of type 2 diabetes. The role of genetic factors in the development of obesity has been broadly recognized. Adiponectin's level is inversely correlated with body fat percentage and is reduced in obesity and type 2 diabetes. The aim of this study is to investigate the association between WHtR and adiponectin gene polymorphisms in Iranian population. METHODS: This study was conducted on 610 subjects from two Iranian populations. Anthropometric characteristics were measured by routine methods. Blood samples were collected in tubes (3-5 mL) containing EDTA and were stored at 20 degrees C. After DNA extraction, genotyping was performed using PCR-RFLP technique. RESULTS: There were statistically significant differences in genotype frequencies of -11391 G/A in centrally obese (WHtR >0.5) and noncentrally obese (WHtR <=0.5) subjects (P value <0.044). In the former, the frequencies of GG and GA + AA genotypes were 89.4 and 10.6 %, respectively, while the frequencies of GG and GA + AA genotypes were 95.9 and 4.1 %, respectively, in noncentrally obese subjects. CONCLUSIONS: The frequency of GG genotype was significantly increased in subjects with WHtR >0.5 compared to the other group. After adjustment for diabetes, abdominal obesity was significantly associated with the -11391 G/A polymorphism. PMID- 26902744 TI - Prevalence of orthorexia nervosa is less than 1 %: data from a US sample. AB - PURPOSE: Orthorexia nervosa, or pathological dieting based on being "healthy," has been of growing interest. Clinical data are limited to less than a half-dozen case studies reporting instances of medical problems due to healthful eating. However, more than a dozen studies using a measure to identify orthorexia, the ORTO-15, report very high prevalence rates in non-clinical samples. Point prevalence rates are reported from 6 % to nearly 90 %. Such variability could be due to cultural issues or psychometric problems with the instrument. This study examines prevalence rate of orthorexia in a US sample. METHOD: The ORTO-15 was administered to 275 US college students along with other questions regarding diet, exercise, and health. RESULTS: While the ORTO-15 indicated a prevalence rate of 71 %, only 20 % of the sample endorsed a dietary practice of removing a particular food type (e.g. meat) from their diet. Those who endorsed following a vegan diet had the highest (less pathological) mean ORTO-15 score. Further, when classifying participants based on their seriousness about healthy eating and whether their diet had led to impairment in everyday activities and medical problems, less than 1 % of the sample fell into such a category. CONCLUSION: As in other countries, a large proportion of a non-clinical US sample scored in the orthorexia range on the ORTO-15. However, this instrument is likely unable to distinguish between healthy eating and pathologically healthful eating. Our estimate is that orthorexia nervosa like anorexia nervosa and bulimia nervosa, is not a common condition. PMID- 26902746 TI - Passivity, being-with and being-there: care during birth. AB - This paper examines how to best be with women during birth, based on a phenomenological description of the birth experience. The first part of the paper establishes birth as an uncanny experience, that is, an experience that is not only entirely unfamiliar, but even unimaginable. The way in which birth happens under unknowable circumstances (in terms of when, how, with whom...) creates a set of anxieties on top of the fundamental anxiety that emerges from the existential paradox by which it does not seem possible for a body to give birth to another body. Would homebirth provide a remedy to the uncanniness? The result yielded by medical studies is confirmed by the phenomenological perspective taken here: homebirth might be reassuring for some, but not for everybody; choice of birth place is important. Once the birth process starts happening, another layer of strangeness is added: it turns out to be an experience of radical passivity and waiting, normally. The question thus becomes how to best care for somebody who is exposed to uncanniness, passivity, and waiting. Martin Heidegger's concepts of care and discourse prove useful in examining how to facilitate rather than interrupt this process. It becomes necessary to think beyond verbal communication towards a wider concept of communication that involves silence and intercorporeality. Birth requires a special kind of being-with as being-there. PMID- 26902747 TI - Ultrafast (1 MUs) Mixing and Fast Protein Folding in Nanodrops Monitored by Mass Spectrometry. AB - The use of theta-glass emitters and mass spectrometry to monitor reactions that occur as fast as one MUs is demonstrated. Acidified aqueous solutions containing unfolded proteins are mixed with aqueous ammonium acetate solutions to increase the solution pH and induce protein folding during nanoelectrospray ionization. Protein charge-state distributions show the extent to which folding occurs, and reaction times are obtained from known protein folding time constants. Shorter reaction times are obtained by decreasing the solution flow rate, and reaction times between 1.0 and 22 MUs are obtained using flow rates between 48 and 2880 pL/s, respectively. Remarkably similar reaction times are obtained for three different proteins (Trp-cage, myoglobin, and cytochrome c) with folding time constants that differ by more than an order of magnitude (4.1, 7, and 57 MUs, respectively), indicating that the reaction times obtained using rapid mixing from theta-glass emitters are independent of protein identity. A folding time constant of 2.2 MUs is obtained for the formation of a beta-hairpin structure of renin substrate tetradecapeptide, which is the fastest folding event measured using a rapid mixing technique. The 1.0 MUs reaction time obtained here is about an order of magnitude lower than the shortest reaction time probed using a conventional mixer (8 MUs). Moreover, this fast reaction time is obtained with a 48 pL/s flow rate, which is 2000-times less than the flow rate required to obtained the 8 MUs reaction time using a conventional mixer. These results indicate that rapid mixing with theta-glass emitters can be used to access significantly faster reaction times while consuming substantially less sample than in conventional mixing apparatus. PMID- 26902748 TI - Comparison of range of motion tests with throwing kinematics in elite team handball players. AB - The aim of this study was to compare the active and passive range of motion (ROM) of the glenohumeral external rotation with the maximal external rotation and throwing performance during different throws with different wind-up techniques in elite team handball players. Twenty-two elite team handball players participated in the study in which the maximal ball release velocity and maximal external rotation during standing, with run-up and jump throws with two types of wind-ups were measured together with the maximal active and passive glenohumeral ROM of the external rotation, lying supine on a bench. Higher maximal external rotation was found during the throws with the whip-like wind-up in comparison to circular like wind-up throws together with a lower external rotation during the active ROM test. No correlations were found between the ROM of the external rotation with the maximal ball release velocity and the maximal external rotation measured during the throws. It was concluded that ROM of the external rotation measured on the bench does not give any information about the maximal throwing performance or the external rotation angle during throwing and therefore cannot be used to identify potential fast throwers or injuries in elite team handball players. PMID- 26902750 TI - Adapting Health Education for the Internet Age. PMID- 26902749 TI - Monocyte-induced recovery of inflammation-associated hepatocellular dysfunction in a biochip-based human liver model. AB - Liver dysfunction is an early event in sepsis-related multi-organ failure. We here report the establishment and characterization of a microfluidically supported in vitro organoid model of the human liver sinusoid. The liver organoid is composed of vascular and hepatocyte cell layers integrating non-parenchymal cells closely reflecting tissue architecture and enables physiological cross communication in a bio-inspired fashion. Inflammation-associated liver dysfunction was mimicked by stimulation with various agonists of toll-like receptors. TLR-stimulation induced the release of pro- and anti-inflammatory cytokines and diminished expression of endothelial VE-cadherin, hepatic MRP-2 transporter and apolipoprotein B (ApoB), resulting in an inflammation-related endothelial barrier disruption and hepatocellular dysfunction in the liver organoid. However, interaction of the liver organoid with human monocytes attenuated inflammation-related cell responses and restored MRP-2 transporter activity, ApoB expression and albumin/urea production. The cellular events observed in the liver organoid closely resembled pathophysiological responses in the well-established sepsis model of peritoneal contamination and infection (PCI) in mice and clinical observations in human sepsis. We therefore conclude that this human liver organoid model is a valuable tool to investigate sepsis-related liver dysfunction and subsequent immune cell-related tissue repair/remodeling processes. PMID- 26902752 TI - Effect of doping beta-NiOOH with Co on the catalytic oxidation of water: DFT+U calculations. AB - Electrocatalytic water splitting using energy from sunlight represents a promising strategy for clean, low-cost, and environmentally friendly production of H2. Unfortunately, the oxygen evolution reaction (OER) at the anode is kinetically slow and represents the bottleneck of this process. Transition metal oxides are good candidates for the anode in electrochemical water splitting. Inspired by recent computational work on beta-NiOOH, which is considered the active phase during the charging and discharging process in alkaline batteries, we performed density functional theory calculations with the inclusion of the Hubbard-U correction on selected surfaces of pure and Co-doped beta-NiOOH to calculate the energetics of the OER. The goal of the paper is to investigate theoretically whether doping a NiOOH surface with Co might change the mechanism and lower the overpotential of the OER on a specific NiOOH surface, and to what extent the choice of the surface unit cell may affect the results. Our results indicate that the most likely reaction mechanism depends on the amount of Co doping. We find that doping the beta-NiOOH surface with only 25% Co decreases the overpotential from 0.28 to 0.18 V. We also find that the theoretical overpotential, and which step is the potential limiting step, depends on the size of the surface unit cell selected in the calculations. This work highlights how optimizing the binding energies of the various intermediates (O, OH and H2O) on the Ni and Co surface sites, may be key to reducing the overpotential. PMID- 26902751 TI - A novel mutation in TRPV3 gene causes atypical familial Olmsted syndrome. AB - Olmsted syndrome (OS) is a rare keratinization disorder, typically characterized by two primary diagnostic hallmarks--mutilating palmoplanter and periorificial keratoderma. However, there's a growing body of literature reporting on the phenotypic diversity of OS, including the absence of aforementioned hallmarks and the presence of some unusual clinical features. Here we presented an atypical familial case of OS that could be confused with Huriez syndrome due to the presence of a scleodactyly-like appearance and tapered fingers in the proband. We ruled out this possibility and made a definitive diagnosis of OS based on clinical features and a genetic assay. Recently, mutations in TRPV3 associated with autosomal dominant or recessive OS continued to be reported, thus conducing to clarifying the underlying relationship between the genotype and phenotype of OS. So we further explored the genotype-phenotype correlation by integrating functionl assays with in silico predictions. Our research not only redefined the phenotypic spectrum of OS, but also provided concrete molecular insights into how mutations in a single gene can lead to significant differences in the severity of this rare disease. PMID- 26902753 TI - Comments on Kreuzer et al.: Dialysis-dependent acute kidney injury in children with end-stage liver disease: prevalence, dialysis modalities and outcome. PMID- 26902754 TI - Dialysis-dependent acute kidney injury in children with end-stage liver disease: response to Deep et al. PMID- 26902755 TI - A holey pursuit: lumen formation in the developing kidney. AB - The formation of polarized epithelial tubules is a hallmark of kidney development. One of the fundamental principles in tubulogenesis is that epithelia coordinate the polarity of individual cells with the surrounding cells and matrix. A central feature in this process is the segregation of membranes into spatially and functionally distinct apical and basolateral domains, and the generation of a luminal space at the apical surface. This review examines our current understanding of the cellular and molecular mechanisms that underlie the establishment of apical-basal polarity and lumen formation in developing renal epithelia, including the roles of cell-cell and cell-matrix interactions and polarity complexes. We highlight growing evidence from animal models, and correlate these findings with models of tubulogenesis from other organ systems, and from in vitro studies. PMID- 26902756 TI - HIV-1 Alters Intestinal Expression of Drug Transporters and Metabolic Enzymes: Implications for Antiretroviral Drug Disposition. AB - This study investigated the effects of HIV-1 infection and antiretroviral therapy (ART) on the expression of intestinal drug efflux transporters, i.e., P glycoprotein (Pgp), multidrug resistance-associated proteins (MRPs), and breast cancer resistance protein (BCRP), and metabolic enzymes, such as cytochrome P450s (CYPs), in the human upper intestinal tract. Intestinal biopsy specimens were obtained from HIV-negative healthy volunteers, ART-naive HIV-positive (HIV(+)) subjects, and HIV(+) subjects receiving ART (10 in each group). Intestinal tissue expression of drug transporters and metabolic enzymes was examined by microarray, real-time quantitative reverse transcription-PCR (qPCR), and immunohistochemistry analyses. Microarray analysis demonstrated significantly lower expression of CYP3A4 and ABCC2/MRP2 in the HIV(+) ART-naive group than in uninfected subjects. qPCR analysis confirmed significantly lower expression of ABCC2/MRP2 in ART-naive subjects than in the control group, while CYP3A4 and ABCG2/BCRP showed a trend toward decreased expression. Protein expression of MRP2 and BCRP was also significantly lower in the HIV(+) naive group than in the control group and was partially restored to baseline levels in HIV(+) subjects receiving ART. In contrast, gene and protein expression of ABCB1/Pgp was significantly increased in HIV(+) subjects on ART relative to HIV(+) ART-naive subjects. These data demonstrate that the expression of drug-metabolizing enzymes and efflux transporters is significantly altered in therapy-naive HIV(+) subjects and in those receiving ART. Since CYP3A4, Pgp, MRPs, and BCRP metabolize or transport many antiretroviral drugs, their altered expression with HIV infection may negatively impact drug pharmacokinetics in HIV(+) subjects. This has clinical implications when using data from healthy volunteers to guide ART. PMID- 26902758 TI - Combined Bioinformatic and Rational Design Approach To Develop Antimicrobial Peptides against Mycobacterium tuberculosis. AB - Drug-resistant pathogens are a growing problem, and novel strategies are needed to combat this threat. Among the most significant of these resistant pathogens is Mycobacterium tuberculosis, which is an unusually difficult microbial target due to its complex membrane. Here, we design peptides for specific activity against M. tuberculosis using a combination of "database filtering" bioinformatics, protein engineering, and de novo design. Several variants of these peptides are structurally characterized to validate the design process. The designed peptides exhibit potent activity (MIC values as low as 4 MUM) against M. tuberculosis and also exhibit broad activity against a host of other clinically relevant pathogenic bacteria such as Gram-positive bacteria (Streptococcus) and Gram negative bacteria (Escherichia coli). They also display excellent selectivity, with low cytotoxicity against cultured macrophages and lung epithelial cells. These first-generation antimicrobial peptides serve as a platform for the design of antibiotics and for investigating structure-activity relationships in the context of the M. tuberculosis membrane. The antimicrobial peptide design strategy is expected to be generalizable for any pathogen for which an activity database can be created. PMID- 26902757 TI - Distinct Pharmacodynamic Activity of Rilpivirine in Ectocervical and Colonic Explant Tissue. AB - A long-acting injectable form of rilpivirine (RPV) is being evaluated in clinical trials for the prevention of HIV infection. Preclinical testing was undertaken to define RPV pharmacokinetic (PK) and pharmacodynamic (PD) activities in ectocervical and colonic tissue treated in vitro Tenfold dilutions of RPV were added to the basolateral medium of polarized ectocervical and colonic explant tissues. To half the explants, HIV-1BaL was applied to the apical tissue surface. After culture overnight, all the explants were washed and the RPV in the explants not exposed to HIV was quantified using a validated liquid chromatography-mass spectrometry assay. For efficacy, explants exposed to HIV remained in culture, and supernatants were collected to assess viral replication using a p24 enzyme linked immunosorbent assay. The data were log10 transformed, and PK/PD correlations were determined using GraphPad Prism and SigmaPlot software. The application of RPV to the basolateral medium at 10 MUM and 1 MUM was effective in protecting ectocervical and colonic tissues, respectively, from HIV infection. When the RPV in paired ectocervical and colonic explant tissues was quantified, significant inverse linear correlations (P < 0.001) between p24 and RPV concentrations were obtained; more viral replication was noted at lower drug levels. Using a maximum effect model, RPV concentrations of 271 nM in ectocervical tissue and 45 nM in colonic tissue were needed to achieve a 90% effective concentration (EC90). These data demonstrate that RPV can suppress HIV infection in mucosal tissue but that higher levels of RPV are needed in female genital tract tissue than in gastrointestinal tract tissue for protection. PMID- 26902759 TI - Targeting Fibronectin To Disrupt In Vivo Candida albicans Biofilms. AB - New drug targets are of great interest for the treatment of fungal biofilms, which are routinely resistant to antifungal therapies. We theorized that the interaction of Candida albicans with matricellular host proteins would provide a novel target. Here, we show that an inhibitory protein (FUD) targeting Candida fibronectin interactions disrupts biofilm formation in vitro and in vivo in a rat venous catheter model. The peptide appears to act by blocking the surface adhesion of Candida, halting biofilm formation. PMID- 26902760 TI - Incorporating Stage-Specific Drug Action into Pharmacological Modeling of Antimalarial Drug Treatment. AB - Pharmacological modeling of antiparasitic treatment based on a drug's pharmacokinetic and pharmacodynamic properties plays an increasingly important role in identifying optimal drug dosing regimens and predicting their potential impact on control and elimination programs. Conventional modeling of treatment relies on methods that do not distinguish between parasites at different developmental stages. This is problematic for malaria parasites, as their sensitivity to drugs varies substantially during their 48-h developmental cycle. We investigated four drug types (short or long half-lives with or without stage specific killing) to quantify the accuracy of the standard methodology. The treatment dynamics of three drug types were well characterized with standard modeling. The exception were short-half-life drugs with stage-specific killing (i.e., artemisinins) because, depending on time of treatment, parasites might be in highly drug-sensitive stages or in much less sensitive stages. We describe how to bring such drugs into pharmacological modeling by including additional variation into the drug's maximal killing rate. Finally, we show that artemisinin kill rates may have been substantially overestimated in previous modeling studies because (i) the parasite reduction ratio (PRR) (generally estimated to be 10(4)) is based on observed changes in circulating parasite numbers, which generally overestimate the "true" PRR, which should include both circulating and sequestered parasites, and (ii) the third dose of artemisinin at 48 h targets exactly those stages initially hit at time zero, so it is incorrect to extrapolate the PRR measured over 48 h to predict the impact of doses at 48 h and later. PMID- 26902761 TI - Model-Based Phase 3 Dose Selection for HIV-1 Attachment Inhibitor Prodrug BMS 663068 in HIV-1-Infected Patients: Population Pharmacokinetics/Pharmacodynamics of the Active Moiety, BMS-626529. AB - BMS-663068 is an oral prodrug of the HIV-1 attachment inhibitor BMS-626529, which prevents viral attachment to host CD4(+) T cells by binding to HIV-1 gp120. To guide dose selection for the phase 3 program, pharmacokinetic/pharmacodynamic modeling was performed using data from two phase 2 studies with HIV-1-infected subjects (n = 244). BMS-626529 population pharmacokinetics were described by a two-compartment model with first-order elimination from the central compartment, zero-order release of prodrug from the extended-release formulation into a hypothetical absorption compartment, and first-order absorption into the central compartment. The covariates of BMS-663068 formulation type, lean body mass, baseline CD8(+) T-cell percentage, and ritonavir coadministration were found to be significant contributors to intersubject variability. Exposure-response analyses showed a relationship between the loge-transformed concentration at the end of a dosing interval (Ctau) normalized for the protein binding-adjusted BMS 626529 half-maximal (50%) inhibitory concentration (PBAIC50) and the change in the HIV-1 RNA level from the baseline level after 7 days of BMS-663068 monotherapy. The probability of achieving a decline in HIV-1 RNA level of >0.5 or >1.0 log10 copies/ml as a function of the loge-transformed PBAIC50-adjusted Ctau after 7 days of monotherapy was 99 to 100% and 57 to 73%, respectively, for proposed BMS-663068 doses of 400 mg twice daily (BID), 600 mg BID (not studied in the phase 2b study), 800 mg BID, 600 mg once daily (QD), and 1,200 mg QD. On the basis of a slight advantage in efficacy of BID dosing over QD dosing, similar responses for the 600- and 800-mg BID doses, and prior clinical observations, BMS 663068 at 600 mg BID was predicted to have the optimal benefit-risk profile and selected for further clinical investigation. (The phase 2a proof-of-concept study AI438006 and the phase 2b study AI438011 are registered at ClinicalTrials.gov under numbers NCT01009814 and NCT01384734, respectively.). PMID- 26902762 TI - Compensatory Mutations of Rifampin Resistance Are Associated with Transmission of Multidrug-Resistant Mycobacterium tuberculosis Beijing Genotype Strains in China. AB - Mycobacterium tuberculosis can acquire resistance to rifampin (RIF) through mutations in the rpoB gene. This is usually accompanied by a fitness cost, which, however, can be mitigated by secondary mutations in the rpoA or rpoC gene. This study aimed to identify rpoA and rpoC mutations in clinical M. tuberculosis isolates in northern China in order to clarify their role in the transmission of drug-resistant tuberculosis (TB). The study collection included 332 RIF-resistant and 178 RIF-susceptible isolates. The majority of isolates belonged to the Beijing genotype (95.3%, 486/510 isolates), and no mutation was found in rpoA or rpoC of the non-Beijing genotype strains. Among the Beijing genotype strains, 27.8% (89/320) of RIF-resistant isolates harbored nonsynonymous mutations in the rpoA (n = 6) or rpoC (n = 83) gene. The proportion of rpoC mutations was significantly higher in new cases (P = 0.023) and in strains with the rpoB S531L mutation (P < 0.001). In addition, multidrug-resistant (MDR) strains with rpoC mutations were significantly associated with 24-locus mycobacterial interspersed repetitive-unit-variable-number tandem-repeat clustering (P = 0.016). In summary, we believe that these findings indirectly suggest an epistatic interaction of particular mutations related to RIF resistance and strain fitness and, consequently, the role of such mutations in the spread of MDR M. tuberculosis strains. PMID- 26902763 TI - Transmission-Blocking Potential of MEFAS, a Hybrid Compound Derived from Artesunate and Mefloquine. AB - Most antimalarial drugs target asexual parasites without reducing gametocyte formation or development. Drugs with dual roles, i.e., those that can target both asexual parasites and gametocytes, would improve the control of malaria. In the current study, MEFAS, a hybrid drug derived from mefloquine and artesunate that has been shown to be an active blood schizonticidal drug, was assessed to determine its ability to block the infectivity of Plasmodium falciparum gametocytes. MEFAS was 280 and 15 times more effective than mefloquine alone and artesunate alone, respectively. PMID- 26902764 TI - Pharmacokinetic Variability of Daptomycin during Prolonged Therapy for Bone and Joint Infections. AB - The interindividual and intraindividual variabilities in daptomycin pharmacokinetics were investigated in 23 patients (69 pharmacokinetic profiles) who were treated for several months for bone and joint infections. Population daptomycin clearance was significantly influenced by renal function and was significantly higher in male than in female patients. We observed significant intraindividual changes in daptomycin clearance, which were uncorrelated with changes in renal function, suggesting that therapeutic drug monitoring is important in patients receiving prolonged daptomycin therapy. PMID- 26902765 TI - An Open, Randomized, Single-Center, Crossover Pharmacokinetic Study of Meropenem after Intraperitoneal and Intravenous Administration in Patients Receiving Automated Peritoneal Dialysis. AB - The objective of this study was to determine the pharmacokinetic profile of meropenem in automated peritoneal dialysis (APD) patients. In 6 patients without peritonitis, a single dose of 0.5 g of meropenem was applied intraperitoneally (i.p.) or intravenously (i.v.) and concentrations in serum and dialysate were measured at specified intervals over 24 h with high-performance liquid chromatography-mass spectrometry. The mean maximum concentrations of meropenem in serum (Cmax) were 27.2 mg/liter (standard deviation [SD], +/-6.9) and 10.1 mg/liter (SD, +/-2.5) and in dialysate were 3.6 mg/liter (SD, +/-2.3) and 185.8 mg/liter (SD, +/-18.7) after i.v. and i.p. administrations, respectively. The mean areas under the curve from 0 to 24 (AUC0-24) of meropenem in serum were 173.5 mg . h/liter (SD, +/-29.7) and 141.4 mg . h/liter (SD, +/-37.5) (P = 0.046) and in dialysate were 42.6 mg . h/liter (SD, +/-20.0) and 623.4 mg . h/liter (SD, +/-84.1) (P = 0.028) after i.v. and i.p. administrations, respectively. The ratios for dialysate exposure over plasma exposure after i.v. and i.p. treatments were 0.2 (SD, +/-0.1) and 4.6 (SD, +/-0.9), respectively (P = 0.031). A mean target value of 40% T>MIC (time for which the free meropenem concentration exceeds the MIC) for clinically relevant pathogens with EUCAST susceptibility breakpoints of 2 mg/liter was reached in serum after i.p. and i.v. administrations and in dialysate after i.p. but not after i.v. administration. The present data indicate that low i.p. exposure limits the i.v. use of meropenem for PD-associated peritonitis. In contrast, i.p. administration not only results in superior concentrations in dialysate but also might be used to treat systemic infections. PMID- 26902766 TI - Differential In Vitro and In Vivo Toxicities of Antimicrobial Peptide Prodrugs for Potential Use in Cystic Fibrosis. AB - There has been considerable interest in the use of antimicrobial peptides (AMPs) as antimicrobial agents for the treatment of many conditions, including cystic fibrosis (CF). The challenging conditions of the CF patient lung require robust AMPs that are active in an environment of high proteolytic activity but that also have low cytotoxicity and immunogenicity. Previously, we developed prodrugs of AMPs that limited the cytotoxic effects of AMP treatment by rendering the antimicrobial activity dependent on the host enzyme neutrophil elastase (NE). However, cytotoxicity remained an issue. Here, we describe the further optimization of the AMP prodrug (pro-AMP) model for CF to produce pro-WMR, a peptide with greatly reduced cytotoxicity (50% inhibitory concentration against CFBE41o- cells, >300 MUM) compared to that of the previous group of pro-AMPs. The bactericidal activity of pro-WMR was increased in NE-rich bronchoalveolar lavage (BAL) fluid from CF patients (range, 8.4% +/- 6.9% alone to 91.5% +/- 5.8% with BAL fluid; P = 0.0004), an activity differential greater than that of previous pro-AMPs. In a murine model of lung delivery, the pro-AMP modification reduced host toxicity, with pro-WMR being less toxic than the active peptide. Previously, host toxicity issues have hampered the clinical application of AMPs. However, the development of application-specific AMPs with modifications that minimize toxicity similar to those described here can significantly advance their potential use in patients. The combination of this prodrug strategy with a highly active AMP has the potential to produce new therapeutics for the challenging conditions of the CF patient lung. PMID- 26902767 TI - A Flow Cytometry Method for Rapidly Assessing Mycobacterium tuberculosis Responses to Antibiotics with Different Modes of Action. AB - Current methods for assessing the drug susceptibility of Mycobacterium tuberculosis are lengthy and do not capture information about viable organisms that are not immediately culturable under standard laboratory conditions as a result of antibiotic exposure. We have developed a rapid dual-fluorescence flow cytometry method using markers for cell viability and death. We show that the fluorescent marker calcein violet with an acetoxy-methyl ester group (CV-AM) can differentiate between populations of M. tuberculosis growing at different rates, while Sytox green (SG) can differentiate between live and dead mycobacteria. M. tuberculosis was exposed to isoniazid or rifampin at different concentrations over time and either dual stained with CV-AM and SG and analyzed by flow cytometry or plated to determine the viability of the cells. Although similar trends in the loss of viability were observed when the results of flow cytometry and the plate counting methods were compared, there was a lack of correlation between these two approaches, as the flow cytometry analysis potentially captured information about cell populations that were unable to grow under standard conditions. The flow cytometry approach had an additional advantage in that it could provide insights into the mode of action of the drug: antibiotics targeting the cell wall gave a flow cytometry profile distinct from those inhibiting intracellular processes. This rapid drug susceptibility testing method could identify more effective antimycobacterials, provide information about their potential mode of action, and accelerate their progress to the clinic. PMID- 26902768 TI - The Central Hinge Link Truncation of the Antimicrobial Peptide Fowlicidin-3 Enhances Its Cell Selectivity without Antibacterial Activity Loss. AB - Antimicrobial peptides (AMPs) have been paid considerable attention because of their broad-spectrum antimicrobial activity and a reduced possibility of the development of bacterial drug resistance. Fowlicidin-3 (Fow-3) is an identified type of chicken cathelicidin AMP that has exhibited considerable antimicrobial activity and cytotoxicity. To reduce cell toxicity and improve cell selectivity, several truncated peptides of fowlicidin-3, Fow-3(1-15), Fow-3(1-19), Fow-3(1-15 20-27), and Fow-3(20-27), were synthesized. Our results indicated that neither the N- nor C-terminal segment alone [Fow-3(1-15), Fow-3(1-19), Fow-3(20-27)] was sufficient to confer antibacterial activity. However, Fow-3(1-19) with the inclusion of the central hinge link (-AGIN-) retained substantial cell toxicity, which other analogs lost. Fow-3(1-15-20-27) displayed potent antimicrobial activity for a wide range of Gram-negative and Gram-positive bacteria and no obvious hemolytic activity or cytotoxicity. The central link region was shown to be critically important in the function of cell toxicity but was not relevant to antibacterial activity. Fow-3(1-15-20-27) maintained antibacterial activity in the presence of physiological concentrations of salts. The results from fluorescence spectroscopy, scanning electron microcopy, and transmission electron microcopy showed that Fow-3(1-15-20-27) as well as fowlicidin-3 killed bacterial cells by increasing membrane permeability and damaging the membrane envelope integrity. Fow-3(1-15-20-27) could be a promising antimicrobial agent for clinical application. PMID- 26902769 TI - Rare Detection of the Acinetobacter Class D Carbapenemase blaOXA-23 Gene in Proteus mirabilis. PMID- 26902770 TI - Complete Nucleotide Sequence of pKOI-34, an IncL/M Plasmid Carrying blaIMP-34 in Klebsiella oxytoca Isolated in Japan. AB - We determined the complete nucleotide sequence of a self-transmissible IncL/M plasmid, pKOI-34, from a Klebsiella oxytoca isolate. pKOI-34 possessed the core structure of an IncL/M plasmid found in Erwinia amylovora, pEL60, with two mobile elements inserted, a transposon carrying the arsenic resistance operon and a Tn21 like core module (tnp and mer modules) piggybacking blaIMP-34 as a class 1 integron, In808, where blaIMP-34 confers a resistance to carbapenems in K. oxytoca and Klebsiella pneumoniae. PMID- 26902772 TI - Novel naproxen/esomeprazole magnesium compound pellets based on acid-independent mechanism: in vitro and in vivo evaluation. AB - The purpose of this study was to develop the novel naproxen/esomeprazole magnesium compound pellets (novel-NAP/EMZ) depending on EMZ acid-independent mechanism which has been proved to be predominate in the mechanism of co-therapy with nonsteroidal anti-inflammatory drug. The novel-NAP/EMZ compound pellets, composed of NAP colon-specific pellets (NAP-CSPs) and EMZ modified-release pellets (EMZ-MRPs), were prepared by fluid-bed coating technology with desired in vitro release profiles. The resulting pellets were filled into hard gelatin capsules for in vivo evaluation in rats and compared with the reference compound pellets, consisted of NAP enteric-coated pellets (NAP-ECPs) and EMZ immediate release pellets (EMZ-IRPs). The reference compound pellets were prepared simulating the drug delivery system of VIMOVO((r)). In vivo pharmacokinetics, EMZ MRPs had significantly larger AUC0-t (p < 0.01), 1.67 times more than that of EMZ IRPs, and prolonged mean residence time (7.55 +/- 0.12 h) than that of IRPs (1.46 +/- 0.39 h). NAP-CSPs and NAP-ECPs showed similar AUC0-t. Compared to the reference compound pellets, the novel-NAP/EMZ compound pellets did not show distinct differences in histological mucosal morphology. However, biochemical tests exhibited enhanced total antioxidant capacity, increased nitric oxide content and reduced malondialdehyde level for novel-NAP/EMZ compound pellets, indicating that the acid-independent action took effect. The gastric pH values of novel-NAP/EMZ compound pellets were at a low and stable level, which could ensure normal physiological range of human gastric pH. As a result, the novel-NAP/EMZ compound pellets may be a more suitable formulation with potential advantages by improving bioavailability of drug and further reducing undesirable gastrointestinal damages. PMID- 26902773 TI - Pediatric Hospital Discharges to Home Health and Postacute Facility Care: A National Study. AB - IMPORTANCE: Acute care hospitals are challenged to provide efficient, high quality care to children who have medically complex conditions and may require weeks or months for recovery. Although the use of home health care (HHC) and facility-based postacute care (PAC) after discharge is well documented for adults, to our knowledge, little is known for children. OBJECTIVE: To assess the national prevalence of, characteristics of children discharged to, and variation in use across states of HHC and PAC for children. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of 2,423,031 US acute care hospital discharges in 2012 for patients ages 0 to 21 years from the nationally representative Agency for Healthcare Research and Quality Kids' Inpatient Database. MAIN OUTCOMES AND MEASURES: Discharges to HHC (eg, visiting or private duty home nursing) and PAC (eg, rehabilitation facility) were identified from Centers for Medicare and Medicaid Services Discharge Status Codes. We compared children's characteristics (eg, race/ethnicity and number of chronic conditions) by discharge type using generalized linear regression. RESULTS: The median age of participants was 3 years (interquartile range, 0-13 years), and 45.6% were female. Of 2,423,031 US acute care hospital discharges in 2012 for patients ages 0 to 21 years, 122,673 discharges (5.1%) were to HHC and 26,282 (1.1%) were to PAC facilities. Neonatal care was the most common reason (44.5%, n = 54,589) for acute care hospitalization with discharge to HHC. Nonneonatal respiratory, musculoskeletal, and trauma-related problems, collectively, were the most common reasons for discharge to PAC (42.9%, n = 11,275). When compared with PAC, more discharges to HHC had no chronic condition (34.4% vs 18.0%, P < .001) and fewer discharges to HHC had 4 or more chronic conditions (22.5% vs 37.7%, P < .001). In multivariable analysis, Hispanic children were less likely to use PAC (0.8% vs 1.1%; odds ratio [OR], 0.9 [95% CI, 0.8-0.9]) or HHC (3.3% vs 5.5%; OR, 0.8 [95% CI, 0.7-0.8]) compared with other children. Children with 4 or more chronic conditions compared with no chronic conditions had a higher likelihood of HHC use (11.0% vs 4.4%; OR, 2.9 [95% CI, 2.8-3.0]) and PAC (3.9% vs 0.8%; OR, 4.5 [95% CI, 4.3-4.9]). After case-mix adjustment, there was significant (P < .001) variation across states in HHC (range, 0.4%-24.5%) and PAC (range, 0.4%-4.9%) use. CONCLUSIONS AND RELEVANCE: Home health care and PAC use after discharge for hospitalized children is infrequent, even for children with multiple chronic conditions. It varies significantly by race/ethnicity and across states. Further investigation is needed to assess reasons for this variation and to determine for which children HHC and PAC are most effective. PMID- 26902774 TI - Appropriating Video Surveillance for Art and Environmental Awareness: Experiences from ARTiVIS. AB - Arts, Real-Time Video and Interactivity for Sustainability (ARTiVIS) is an ongoing collaborative research project investigating how real-time video, DIY surveillance technologies and sensor data can be used as a tool for environmental awareness, activism and artistic explorations. The project consists of a series of digital contexts for aesthetic contemplation of nature and civic engagement, aiming to foster awareness and empowerment of local populations through DIY surveillance. At the core of the ARTIVIS efforts are a series of interactive installations (namely B-Wind!, Hug@tree and Play with Fire), that make use of surveillance technologies and real-time video as raw material to promote environmental awareness through the emotion generated by real-time connections with nature. Throughout the project development, the surveillance concept has been shifting from the use of surveillance technology in a centralized platform, to the idea of veillance with distributed peer-to-peer networks that can be used for science and environmental monitoring. In this paper we present the history of the ARTiVIS project, related and inspiring work, describe ongoing research work and explore the present and future challenges of appropriating surveillance technology for artistic, educational and civic engagement purposes. PMID- 26902771 TI - From Drug Screening to Target Deconvolution: a Target-Based Drug Discovery Pipeline Using Leishmania Casein Kinase 1 Isoform 2 To Identify Compounds with Antileishmanial Activity. AB - Existing therapies for leishmaniases present significant limitations, such as toxic side effects, and are rendered inefficient by parasite resistance. It is of utmost importance to develop novel drugs targeting Leishmania that take these two limitations into consideration. We thus chose a target-based approach using an exoprotein kinase, Leishmania casein kinase 1.2 (LmCK1.2) that was recently shown to be essential for intracellular parasite survival and infectivity. We developed a four-step pipeline to identify novel selective antileishmanial compounds. In step 1, we screened 5,018 compounds from kinase-biased libraries with Leishmania and mammalian CK1 in order to identify hit compounds and assess their specificity. For step 2, we selected 88 compounds among those with the lowest 50% inhibitory concentration to test their biological activity on host-free parasites using a resazurin reduction assay and on intramacrophagic amastigotes using a high content phenotypic assay. Only 75 compounds showed antileishmanial activity and were retained for step 3 to evaluate their toxicity against mouse macrophages and human cell lines. The four compounds that displayed a selectivity index above 10 were then assessed for their affinity to LmCK1.2 using a target deconvolution strategy in step 4. Finally, we retained two compounds, PP2 and compound 42, for which LmCK1.2 seems to be the primary target. Using this four-step pipeline, we identify from several thousand molecules, two lead compounds with a selective antileishmanial activity. PMID- 26902775 TI - Restless Legs Syndrome/Willis-Ekbom Disease and Periodic Limb Movements: A Comprehensive Review of Epidemiology, Pathophysiology, Diagnosis and Treatment Considerations. AB - Restless legs syndrome (RLS) or Willis-Ekbom Disease is a common, but frequently under- recognized and misdiagnosed condition seen in many subspecialty practices including neurology, sleep medicine, primary care and rheumatology. Periodic limb movements are a frequent co-morbid diagnosis in RLS. Despite prior beliefs that the condition was "benign", it has been demonstrated to have a considerable impact on sufferers quality of life, physically and psychologically, as well as socially. This chapter is meant as a comprehensive review of RLS encompassing epidemiology, pathophysiology, diagnosis, and treatment considerations. PMID- 26902777 TI - Opening the Way to Catalytic Aminopalladation/Proxicyclic Dehydropalladation: Access to Methylidene gamma-Lactams. AB - A new aerobic intramolecular palladium(II)-based catalytic system that triggers aminopalladation/dehydropalladation of N-sulfonylalkenylamides to give the corresponding methylidene gamma-lactams has been identified. Use of triphenylphosphine and chloride anion as ligands is mandatory for optimal yields, and molecular oxygen can be used as the sole terminal oxidant. Scope and limitations of the methods are described. A mechanism is proposed on the basis of experimental results as well as density functional theory calculations. PMID- 26902776 TI - TRPV1 function is modulated by Cdk5-mediated phosphorylation: insights into the molecular mechanism of nociception. AB - TRPV1 is a polymodally activated cation channel acting as key receptor in nociceptive neurons. Its function is strongly affected by kinase-mediated phosphorylation leading to hyperalgesia and allodynia. We present behavioral and molecular data indicating that TRPV1 is strongly modulated by Cdk5-mediated phosphorylation at position threonine-407(mouse)/T406(rat). Increasing or decreasing Cdk5 activity in genetically engineered mice has severe consequences on TRPV1-mediated pain perception leading to altered capsaicin consumption and sensitivity to heat. To understand the molecular and structural/functional consequences of TRPV1 phosphorylation, we generated various rTRPV1T406 receptor variants to mimic phosphorylated or dephosphorylated receptor protein. We performed detailed functional characterization by means of electrophysiological whole-cell and single-channel recordings as well as Ca(2+)-imaging and challenged recombinant rTRPV1 receptors with capsaicin, low pH, or heat. We found that position T406 is critical for the function of TRPV1 by modulating ligand sensitivity, activation, and desensitization kinetics as well as voltage dependence. Based on high resolution structures of TRPV1, we discuss T406 being involved in the molecular transition pathway, its phosphorylation leading to a conformational change and influencing the gating of the receptor. Cdk5-mediated phosphorylation of T406 can be regarded as an important molecular switch modulating TRPV1-related behavior and pain sensitivity. PMID- 26902778 TI - The role of a vertical reference point in changing gait regulation in cricket run ups. AB - The need to identify information sources which facilitate a functional coupling of perception and action in representative practice contexts is an important challenge for sport scientists and coaches. The current study investigated the role of visual information in regulating athlete gait behaviours during a locomotor pointing task in cricket. Integration of experiential knowledge of elite coaches and theoretical understanding from previous empirical research led us to investigate whether the presence of an umpire would act as a vertical informational constraint that could constrain the emergent coordination tendencies of cricket bowlers' run-up patterns. To test this idea, umpire presence was manipulated during run-ups of 10 elite medium-fast bowlers. As hypothesised, removal of the umpire from the performance environment did not result in an inability to regulate gait to intercept a target, however, the absence of this informational constraint resulted in the emergence of different movement patterns in participant run-ups. Significantly lower standard deviation values of heel-to-crease distances were observed in the umpire condition at multiple steps, compared to performance in the no-umpire condition. Manipulation of this informational constraint altered gait regulation of participants, offering a mechanism to understand how perception-action couplings can be varied during performance in locomotor pointing tasks in sport. PMID- 26902779 TI - Adherence to Traumatic Brain Injury Guidelines-Linkages to Outcomes. PMID- 26902780 TI - Factors Predicting Poor Outcome in a Surgically Managed Series of Multiple Intracranial Aneurysms. AB - OBJECTIVE: Multiple factors are known to influence outcomes in single-aneurysm subarachnoid hemorrhage, such as Hunt and Hess (H&H) grade, hypertension, etc. We sought to assess the influence of individual risk factors on outcome in surgically managed patients with multiple intracranial aneurysm. METHODS: A retrospective review of consecutive 780 patients of subarachnoid hemorrhage revealed multiple intracranial aneurysm in 63 patients with 146 aneurysms. Clinicoradiologic features, hospital course, and outcome obtained via use of the Glasgow Outcome Score were noted from hospital records. H&H grade was divided into 2 groups as good and poor whereas Glasgow Outcome Score at 1 month was divided into 2 groups as favorable and unfavorable for analysis. To test association among variables, a chi(2) test/Fisher exact test was used. Risk was calculated in exposure group by the use of univariate logistic regression and multivariate analysis (binary logistic regression model). RESULTS: A definite female preponderance was observed (male/female ratio: 1:2.71). The most common site was middle cerebral artery bifurcation (overall and male patients, n = 43); in women, it was internal carotid artery bifurcation. Anterior communicating artery aneurysm was the most common to bleed (n = 22). Early presentation resulted in worse outcomes (<4: 4-21: >21days = 44:37:33, P = .844). Vasospasm and infarct incidence was greatest in the group 4-14 days (n = 37). Infarct evolved in 15 patients (8 in territory of aneurysmal dissection/distribution). Factors influencing patient outcomes were age >=65 years (P = 0.037), H&H grade (P = 0.04), posterior communicating artery distribution of aneurysm (P = 0.03), hypertension (P = 0.03), infarct (P = 0.001), and hydrocephalus (P = 0.01) CONCLUSIONS: Poor H&H grade, hypertension, posterior communicating artery distribution, elderly age, infarct, and hydrocephalus each influenced poor outcomes at 1 month. Hydrocephalus is predictive of poor outcome. PMID- 26902781 TI - Complications Related to the Endoscopic Endonasal Transsphenoidal Approach for Nonfunctioning Pituitary Macroadenomas in 300 Consecutive Patients. AB - OBJECTIVE: To analyze complications of endoscopic transsphenoidal surgery (ETS) for nonfunctioning pituitary macroadenomas (NFPAs). METHODS: A retrospective study of 300 NFPAs was performed. Complications and factors that could influence these complications were analyzed. RESULTS: Visual and pituitary functions worsened in 2.4% and 13.7% of cases, respectively. Postoperative diabetes insipidus was permanent in 6.2% of cases. Postoperative meningitis occurred in 3.3% of patients. Meningitis was strongly associated with intraoperative cerebrospinal fluid (CSF) leaks (P = 0.01), postoperative CSF leaks (P = 0.0001), and operation times longer than 1 hour (P = 0.023). Detection of Staphylococcus aureus and preoperative treatment with mupirocin in the nostrils did not impact the occurrence of meningitis. Two patients with meningitis died (unique causes of death). Postoperative CSF leaks occurred in 2.7% of cases and were associated with intraoperative CSF leaks (P = 0.007) and permanent diabetes insipidus (P = 0.028). The rate of CSF leak decreased from 4% to 0.8% (P = 0.048) after we moved from a soft to hard reconstruction of the sella. The rate of postoperative epistaxis decreased from 6.7% to 1.25% after we stopped using monopolar coagulation (P = 0.013). CONCLUSIONS: ETS permits a wide view, allowing good conditions for a satisfactory resection in the majority of NFPAs. Some pitfalls of endoscopy can lead to complications that improve with modification of the operative technique (i.e., CSF leak and postoperative epistaxis). This study confirms an acceptable rate of complications associated with ETS. PMID- 26902782 TI - The interaction between the dopamine receptor D4 (DRD4) variable number tandem repeat polymorphism and perceived peer drinking norms in adolescent alcohol use and misuse. AB - Peer drinking norms are arguably one of the strongest correlates of adolescent drinking. Prospective studies indicate that adolescents tend to select peers based on drinking (peer selection) and their peers' drinking is associated with changes in adolescent drinking over time (peer socialization). The present study investigated whether the peer selection and socialization processes in adolescent drinking differed as a function of the dopamine receptor D4 (DRD4) variable number tandem repeat genotype in two independent prospective data sets. The first sample was 174 high school students drawn from a two-wave 6-month prospective study. The second sample was 237 college students drawn from a three-wave annual prospective study. Multigroup cross-lagged panel analyses of the high school student sample indicated stronger socialization via peer drinking norms among carriers, whereas analyses of the college student sample indicated stronger drinking-based peer selection in the junior year among carriers, compared to noncarriers. Although replication and meta-analytic synthesis are needed, these findings suggest that in part genetically determined peer selection (carriers of the DRD4 seven-repeat allele tend to associate with peers who have more favorable attitudes toward drinking and greater alcohol use) and peer socialization (carriers' subsequent drinking behaviors are more strongly associated with their peer drinking norms) may differ across adolescent developmental stages. PMID- 26902784 TI - Age Does Not Affect the Material Properties of Expanded Polystyrene Liners in Field-Used Bicycle Helmets. AB - Bicycle helmet foam liners absorb energy during impacts. Our goal was to determine if the impact attenuation properties of expanded polystyrene (EPS) foam used in bicycle helmets change with age. Foam cores were extracted from 63 used and unused bicycle helmets from ten different models spanning an age range of 2 20 yrs. All cores were impact tested at a bulk strain rate of 195 s(-1). Six dependent variables were determined from the stress-strain curve derived from each impact (yield strain, yield stress, elastic modulus, plateau slope, energy at 65% compression, and stress at 65% compression), and a general linear model was used to assess the effect of age on each dependent variable with density as a covariate. Age did not affect any of the dependent variables; however, greater foam density, which varied from 58 to 100 kg/m(3), generated significant increases in all of the dependent variables except for yield strain. Higher density foam cores also exhibited lower strains at which densification began to occur, tended to stay within the plateau region of the stress-strain curve, and were not compressed as much compared with the lower density cores. Based on these data, the impact attenuation properties of EPS foam in field-used bicycle helmets do not degrade with the age. PMID- 26902783 TI - C-C motif ligand 11 reduction in CLL patients serum after vitamin D supplementation. AB - BACKGROUND: Vitamin D (VD) deficiency results in a worse prognosis in patients with chronic lymphocytic leukemia (CLL) and may affect the production of cytokines. Nonetheless, there is the lack of studies dealing with VD supplementation and its impact on chemokines in CLL patients. AIM: The primary endpoint of our interventional study was to evaluate the effect of cholecalciferol supplementation on serum chemokines levels in CLL patients. MATERIALS AND METHODS: Eighteen subjects with CLL were enrolled for the study. Six-month-long cholecalciferol supplementation was performed in CLL patients with serum 25-OH-D3 levels below 30 ng/ml. Cytokines levels were assessed at the beginning of the study and after 6 months. Baseline measurements of cytokines were compared to those in apparently healthy controls. RESULTS: Increased levels of CCL2, CCL3, CCL4, CXCL8, CXCL10, TNFalpha, bFGF, G-CSF, and VEGF were found in CLL patients in comparison with the healthy controls. In the course of the VD supplementation a decrease in serum levels of chemokines CCL11, CCL3, and cytokine PDGF-BB was observed. The decrease of CCL11 was found in CLL patients on VD supplementation solely, whereas the decrease of CCL3 and PDGF-BB was observed in CLL subjects on both chemotherapy and VD supplementation. CONCLUSION: The VD supplementation may exert beneficial effect on chemokines levels in CLL patients with VD deficiency. PMID- 26902785 TI - Laparoscopy for the treatment of ovarian remnant syndrome in four dogs and two cats. AB - OBJECTIVE: To describe the clinical workup and laparoscopic treatment of ovarian remnant syndrome in dogs and cats. MATERIAL AND METHODS: After confirming the diagnosis with some or all of the following tests - vaginoscopy with cytology, hormonal tests, and ultrasound - laparoscopic removal of the ovarian remnants was performed. A three-portal technique was used in the four dogs and a two-portal technique in the two cats. RESULTS: All patients recovered well and were discharged the same day. No post-operative complications occurred in any patient. CONCLUSION AND CLINICAL RELEVANCE: Overall, in the hands of an experienced laparoscopic surgeon, laparoscopic removal of ovarian remnants appears to be a safe procedure in dogs and cats. In addition, laparoscopy offers the advantages of excellent visualization and a reduced morbidity for the patient. Careful case selection and complete pre-operative workup to rule out co-morbidities or underlying neoplasia are important. As with any laparoscopy the surgeon should always be prepared to convert to an open laparotomy if necessary. PMID- 26902786 TI - Recombinant expression, purification and crystallographic studies of the mature form of human mitochondrial aspartate aminotransferase. AB - Mitochondrial aspartate aminotransferase (mAspAT) was recognized as a moonlighting enzyme because it has not only aminotransferase activity but also a high-affinity long-chain fatty acids (LCFA) binding site. This enzyme plays a key role in amino acid metabolism, biosynthesis of kynurenic acid and transport of the LCFA. Therefore, it is important to study the structure-function relationships of human mAspAT protein. In this work, the mature form of human mAspAT was expressed to a high level in Escherichia coli periplasmic space using pET-22b vector, purified by a combination of immobilized metal-affinity chromatography and cation exchange chromatography. Optimal activity of the enzyme occurred at a temperature of 47.5oC and a pH of 8.5. Crystals of human mAspAT were grown using the hanging-drop vapour diffusion method at 277K with 0.1 M HEPES pH 6.8 and 25%(v/v) Jeffamine((r)) ED-2001 pH 6.8. The crystals diffracted to 2.99 A and belonged to the space group P1 with the unit-cell parameters a =56.7, b = 76.1, c = 94.2 A, alpha =78.0, beta =85.6, gamma = 78.4o. Elucidation of mAspAT structure can provide a molecular basis towards understanding catalysis mechanism and substrate binding site of enzyme. PMID- 26902787 TI - Lentivirus-mediated knockdown of CEP55 suppresses cell proliferation of breast cancer cells. AB - Centrosomal protein 55 (CEP55), as a microtubule-bundling protein, plays an important role in cell cycle regulation. CEP55 has been recognized recently in several human cancers. In this study, we first observed that the mRNA level of CEP55 is commonly up-regulated in breast cancer compared with their normal counterparts as demonstrated by data derived from Oncomine database. To further evaluate the functional role of CEP55 in breast cancer cells. Expression of CEP55 was efficiently knocked down using lentivirus-mediated RNA interference in human breast cancer cell line ZR-75-30, as evidenced by quantitative real-time PCR (qRT PCR) and Western blot analysis. Further investigations revealed that CEP55 knockdown significantly inhibited cell proliferation and colony formation. Moreover, flow cytometer analysis indicated knockdown of CEP55 induced cell cycle arrested at G0/G1 phase and cell apoptosis. These findings suggest that CEP55 plays a crucial role in promoting breast cancer cell proliferation and it might be a potential therapeutic target in breast cancer. PMID- 26902788 TI - Total vaginal and single-port total laparoscopic hysterectomy for uterine benign diseases. AB - OBJECTIVE: This study aimed to review the surgical outcomes and health-related quality of life (HRQOL) of total vaginal (TVH) and single-port total laparoscopic hysterectomy (SP-TLH) for uterine benign diseases. STUDY DESIGN: This study included 121 patients who had undergone TVH or SP-TLH for uterine benign diseases between April 2011 and July 2012. Surgical outcomes, complications, and HRQOL were reviewed in the two groups. Preoperative and postoperative HRQOL data from the 36-item Short Form questionnaire (SF-36) were recorded for all patients. RESULTS: TVH was performed more often for the patients who had fewer previous operations (p = 0.32). In the TVH, there were fewer combined surgical procedures (p < 0.01), shorter operation times (p < 0.01), shorter vaginal stump suture times (p = 0.03) and lower complication rates (p < 0.01) than in SP-TLH. Overall, all SF-36 scales improved after surgery, except for the Social Functioning scale. There was no significant difference in any of the scales between the two groups. CONCLUSIONS: TVH has equivalent effects on HRQOL as SP-TLH. SP-TLH is preferred for the cases with complicated and combined procedures. PMID- 26902789 TI - Reversed ageing of Fe3O4 nanoparticles by hydrogen plasma. AB - Magnetite (Fe3O4) nanoparticles suffer from severe ageing effects when exposed to air even when they are dispersed in a solvent limiting their applications. In this work, we show that this ageing can be fully reversed by a hydrogen plasma treatment. By x-ray absorption spectroscopy and its associated magnetic circular dichroism, the electronic structure and magnetic properties were studied before and after the plasma treatment and compared to results of freshly prepared magnetite nanoparticles. While aged magnetite nanoparticles exhibit a more gamma Fe2O3 like behaviour, the hydrogen plasma yields pure Fe3O4 nanoparticles. Monitoring the temperature dependence of the intra-atomic spin dipole contribution to the dichroic spectra gives evidence that the structural, electronic and magnetic properties of plasma treated magnetite nanoparticles can outperform the ones of the freshly prepared batch. PMID- 26902791 TI - A Mobile Application Guiding Patients With Type 1 Diabetes Using Sensor-Augmented Insulin Pump Therapy. PMID- 26902792 TI - Skin Oil Staining to Avoid Infusion Set Cannula Crimping: A Personal Observation. PMID- 26902790 TI - Event and Cost Offsets of Switching 20% of the Type 1 Diabetes Population in Germany From Multiple Daily Injections to Continuous Subcutaneous Insulin Infusion: A 4-Year Simulation Model. AB - BACKGROUND: Most patients with type 1 diabetes (T1D) administer insulin by multiple daily injections (MDI). However, continuous subcutaneous insulin infusion (CSII) therapy has been shown to improve glycemic control compared with MDI. OBJECTIVE: The objective was to determine the key medical event and cost offsets generated over a 4-year period by introducing CSII to T1D patients who have inadequately controlled glucose metabolism on MDI in Germany. METHODS: A decision-analytic budget impact model, simulating a treatment switch scenario, was developed. In the base case, all T1D patients received MDI, while in the switch scenario, 20% of the eligible T1D population, randomly selected, moved to CSII. The model focused on 2 medical endpoints and their corresponding cost offsets: severe hypoglycemic events requiring hospitalization (SHEH) and complication-borne diabetic events (CDEs) avoided. Event rates and costs were taken from the literature and official sources, adopting a health insurance perspective. RESULTS: Compared with the base case, treating 20% of patients with CSII in the switch scenario resulted in 47 864 fewer SHEH and 5543 fewer CDEs. This led to total cost offsets of ?183 085 281 within the 4-year time horizon. Of these, 92% were driven by avoided SHEH. Compared to an expected budget impact (cost increase) of 83%, only treatment costs considered, the total impact of the switch scenario amounted merely to a 24.5% increase in costs (reduction by 58.5% points; a factor of 3.4). CONCLUSION: The use of CSII resulted in fewer SHEH and CDEs compared to MDI. The incurred CSII implementation costs are hence offset to a substantial degree by cost savings in complication treatment. PMID- 26902793 TI - Glucose Meters for Self-Monitoring: Quality Control in Point-of-Care Testing Mode in Hospital Wards. PMID- 26902794 TI - Fundamental Importance of Reference Glucose Analyzer Accuracy for Evaluating the Performance of Blood Glucose Monitoring Systems (BGMSs). AB - BACKGROUND: As blood glucose monitoring system (BGMS) accuracy is based on comparison of BGMS and laboratory reference glucose analyzer results, reference instrument accuracy is important to discriminate small differences between BGMS and reference glucose analyzer results. Here, we demonstrate the important role of reference glucose analyzer accuracy in BGMS accuracy evaluations. METHODS: Two clinical studies assessed the performance of a new BGMS, using different reference instrument procedures. BGMS and YSI analyzer results were compared for fingertip blood that was obtained by untrained subjects' self-testing and study staff testing, respectively. YSI analyzer accuracy was monitored using traceable serum controls. RESULTS: In study 1 (N = 136), 94.1% of BGMS results were within International Organization for Standardization (ISO) 15197:2013 accuracy criteria; YSI analyzer serum control results showed a negative bias (-0.64% to 2.48%) at the first site and a positive bias (3.36% to 6.91%) at the other site. In study 2 (N = 329), 97.8% of BGMS results were within accuracy criteria; serum controls showed minimal bias (<0.92%) at both sites. CONCLUSIONS: These findings suggest that the ability to demonstrate that a BGMS meets accuracy guidelines is influenced by reference instrument accuracy. PMID- 26902796 TI - [Role of heat shock proteins in the cardioprotection of regular moderate alcohol consumption]. AB - BACKGROUND AND OBJECTIVES: To study whether the cardioprotective effect of regular alcohol consumption can be explained by the heat shock proteins (HSP), given their pathogenic role in atherosclerosis. MATERIAL AND METHODS: Cross sectional epidemiological study on 452 men and women aged 40-60. Clinical history, epidemiological survey (frequency of average alcohol consumption) and biochemical analysis was performed; Task Force Chart was applied for classification according to the risk of vascular disease. Intracellular HSPA1A, circulating HSPA1A and HSPD1, and anti-Hsp70/anti-Hsp60 antibodies were quantified by ELISA. RESULTS: Two hundred and thirty-eight (52.7%) were abstemious or drank<20 g/d of alcohol; 123 (27.2%) drank 20-40 g/d, 66 (14.6%) 40 60 g/d and 25>60 g/d (5.5%). Two hundred and thirty-nine had no vascular risk (VR) factor or a risk<5%, 161 had moderate VR (10-20%) and 52 had established atherosclerotic disease. Drinkers of 40-60 g/d showed the highest concentrations of intracellular HSPA1A, which were not significant in subjects with moderate VR. Extracellular HSPA1A didn't differ and HSPD1 was undetectable. Drinkers of 40-60 g/d and moderate VR or atherosclerotic disease presented the lowest concentrations of anti-Hsp70. The highest levels of serum anti-Hsp60 were shown in heavy male drinkers of>60 g/d especially in subjects with moderate VR, and female drinkers of 40-60 g/d. CONCLUSIONS: The cardioprotective effect of 40-60 g/d of alcohol consumption could be due in part, to increased intracellular HSPA1A, a potent anti-inflammatory protein. Excessive intake of alcohol increases antibodies anti-Hsp60, stimulating proinflammatory cytokines. This fact may explain the mortality from cardiovascular disease in heavy drinkers. The clinical application of antibody anti-Hsps quantification has been proposed in patients at risk in order to detect atherosclerotic disease. PMID- 26902797 TI - Camelpox: A brief review on its epidemiology, current status and challenges. AB - Camelpox caused by a Camelpox virus (CMLV) is a very important host specific viral disease of camel. It is highly contagious in nature and causes serious impact on health even mortality of camels and economic losses to the camel owners. It manifests itself either in the local/mild or generalized/severe form. Various outbreaks of different pathogenicity have been reported from camel dwelling areas of the world. CMLV has been characterized in embryonated chicken eggs with the production of characteristic pock lesions and in various cell lines with the capacity to induce giant cells. Being of Poxviridae family, CMLV employs various strategies to impede host immune system and facilitates its own pathogenesis. Both live and attenuated vaccine has been found effective against CMLV infection. The present review gives a comprehensive overview of camelpox disease with respect to its transmission, epidemiology, virion characteristics, viral life cycle, host interaction and its immune modulation. PMID- 26902798 TI - Depression, Fatigue, and QoL in Colorectal Cancer Patients During and After Treatment. AB - In this study, we sought to explore the prevalence of depression and fatigue in colorectal cancer patients during and after treatment to examine how these variables affect quality of life (QoL). In total, 170 patients with colorectal cancer participated in this study. The study population was divided into two groups: one receiving treatment and another that had finished treatment. The results showed that depression and fatigue measurements were higher in patients receiving treatment. Depression was a strong and significant predictor of QoL in both groups, whereas fatigue was not, with the exception of the symptom score. These findings underscore the importance of early detection and management of depression and fatigue during the treatment and survival stages of patients with colorectal cancer. Our findings indicate that health care professionals should provide appropriate nursing intervention to decrease depression and fatigue and enhance patient QoL. PMID- 26902799 TI - Colour Polymorphism Protects Prey Individuals and Populations Against Predation. AB - Colour pattern polymorphism in animals can influence and be influenced by interactions between predators and prey. However, few studies have examined whether polymorphism is adaptive, and there is no evidence that the co-occurrence of two or more natural prey colour variants can increase survival of populations. Here we show that visual predators that exploit polymorphic prey suffer from reduced performance, and further provide rare evidence in support of the hypothesis that prey colour polymorphism may afford protection against predators for both individuals and populations. This protective effect provides a probable explanation for the longstanding, evolutionary puzzle of the existence of colour polymorphisms. We also propose that this protective effect can provide an adaptive explanation for search image formation in predators rather than search image formation explaining polymorphism. PMID- 26902800 TI - Development of siRNA-loaded chitosan nanoparticles targeting Galectin-1 for the treatment of glioblastoma multiforme via intranasal administration. AB - Galectin-1 (Gal-1) is a naturally occurring galactose-binding lectin, which is overexpressed in glioblastoma multiforme (GBM). Gal-1 is associated with tumor progression, and is a potent immune suppressor in the tumor micro-environment. To inhibit Gal-1 in GBM, an effective therapy is required that reaches the central nervous system tumor, with limited systemic effects. In this study, we report for the first time that concentrated chitosan nanoparticle suspensions can deliver small interfering RNA (siRNA) into the central nervous system tumor within hours after intranasal administration. These nanoparticles are able to complex siRNA targeting Gal-1 to a high percentage, and protect them from RNAse degradation. Moreover, a successful intracellular delivery of anti-Gal-1 siRNA resulted in a decreased expression of Gal-1 in both murine and human GBM cells. Sequence specific RNAinterference, resulted in more than 50% Gal-1 reduction in tumor bearing mice. This study indicates that the intranasal pathway is an underexplored transport route for delivering siRNA-based therapies targeting Gal 1 in the treatment of GBM. PMID- 26902801 TI - Malagasy bats shelter a considerable genetic diversity of pathogenic Leptospira suggesting notable host-specificity patterns. AB - Pathogenic Leptospira are the causative agents of leptospirosis, a disease of global concern with major impact in tropical regions. Despite the importance of this zoonosis for human health, the evolutionary and ecological drivers shaping bacterial communities in host reservoirs remain poorly investigated. Here, we describe Leptospira communities hosted by Malagasy bats, composed of mostly endemic species, in order to characterize host-pathogen associations and investigate their evolutionary histories. We screened 947 individual bats (representing 31 species, 18 genera and seven families) for Leptospira infection and subsequently genotyped positive samples using three different bacterial loci. Molecular identification showed that these Leptospira are notably diverse and include several distinct lineages mostly belonging to Leptospira borgpetersenii and L. kirschneri. The exploration of the most probable host-pathogen evolutionary scenarios suggests that bacterial genetic diversity results from a combination of events related to the ecology and the evolutionary history of their hosts. Importantly, based on the data set presented herein, the notable host-specificity we have uncovered, together with a lack of geographical structuration of bacterial genetic diversity, indicates that the Leptospira community at a given site depends on the co-occurring bat species assemblage. The implications of such tight host-specificity on the epidemiology of leptospirosis are discussed. PMID- 26902802 TI - Water level changes affect carbon turnover and microbial community composition in lake sediments. AB - Due to climate change, many lakes in Europe will be subject to higher variability of hydrological characteristics in their littoral zones. These different hydrological regimes might affect the use of allochthonous and autochthonous carbon sources. We used sandy sediment microcosms to examine the effects of different hydrological regimes (wet, desiccating, and wet-desiccation cycles) on carbon turnover. (13)C-labelled particulate organic carbon was used to trace and estimate carbon uptake into bacterial biomass (via phospholipid fatty acids) and respiration. Microbial community changes were monitored by combining DNA- and RNA based real-time PCR quantification and terminal restriction fragment length polymorphism (T-RFLP) analysis of 16S rRNA. The shifting hydrological regimes in the sediment primarily caused two linked microbial effects: changes in the use of available organic carbon and community composition changes. Drying sediments yielded the highest CO2 emission rates, whereas hydrological shifts increased the uptake of allochthonous organic carbon for respiration. T-RFLP patterns demonstrated that only the most extreme hydrological changes induced a significant shift in the active and total bacterial communities. As current scenarios of climate change predict an increase of drought events, frequent variations of the hydrological regimes of many lake littoral zones in central Europe are anticipated. Based on the results of our study, this phenomenon may increase the intensity and amplitude in rates of allochthonous organic carbon uptake and CO2 emissions. PMID- 26902803 TI - The effect of temperature change on the microbial diversity and community structure along the chronosequence of the sub-arctic glacier forefield of Styggedalsbreen (Norway). AB - Microbial communities in the glacier forefield of Styggedalsbreen, Norway, were investigated along a chronosequence from newly exposed soil to vegetated soils using next-generation sequencing of the 16S rRNA gene. In order to monitor the short-term effect of temperature on community successions along the soil gradient, the soil samples were incubated at three different temperatures (5 degrees C, 10 degrees C and 22 degrees C). The microbial community composition along the chronosequence differed according to distance from the glacial terminus and incubation temperature. Samples close to the glacier terminus were dominated by Proteobacteria at 5 degrees C and 10 degrees C, while at 22 degrees C members of Chloroflexi, Acidobacteria and Verrucomicrobia in addition to Proteobacteria accounted for most of the diversity, indicating that sites close to the glacier terminus are more closely related to former subglacial environments. Within the Archaea domain, members of the phylum Euryarchaeota dominated in samples closer to the glacier terminus with a shift to members of the phyla Thaumarchaeota Crenarchaeota with increased soil age. Our data indicate that composition and diversity of the microbial communities along the glacier forefield depend not only on exposure time but are also to a large degree influenced by soil surface temperature and soil maturation. PMID- 26902804 TI - Plasma endotoxin activity in kangaroos with oral necrobacillosis (lumpy jaw disease) using an automated handheld testing system. AB - The aim of the present study was to evaluate the reliability and effectiveness of directly determining endotoxin activity in plasma samples from kangaroos with lumpy jaw disease (LJD, n=15) and healthy controls (n=12). Prior to the present study, the ability of the commercially available automated handheld portable test system (PTS(TM)) to detect endotoxin activity in kangaroo plasma was compared with that of the traditional LAL-kinetic turbidimetric (KT) assay. Plasma samples, which were obtained from endotoxin-challenged cattle, were diluted 1:20 in endotoxin-free water and heated to 80 degrees C for 10 min. The performance of the PTS(TM) was not significantly different from that of the traditional LAL based assay. The data obtained using PTS(TM) correlated with those using KT (r(2)=0.963, P<0.001). These findings indicated that the PTS(TM) is applicable as a simplified system to assess endotoxin activity in macropods. In the present study, we demonstrated the diagnostic value of plasma endotoxin activity in kangaroos with systemic inflammation caused by oral necrobacillosis and identified plasma endotoxin activity as a sensitive marker of systemic inflammation in kangaroos with LJD. Based on ROC curves, we proposed a diagnostic cut-off point for endotoxin activity of >0.22 EU/ml for the identification of LJD. Our results indicate that the assessment of plasma endotoxin activity is a promising diagnostic tool for determining the outcome of LJD in captive macropods. PMID- 26902805 TI - Synovial fluid matrix metalloproteinase-2 and -9 activities in dogs suffering from joint disorders. AB - The activity of matrix metalloproteinase (MMP)-2 and MMP-9 in synovial fluids (SF) sampled from dogs with joint disorders was investigated by gelatin zymography and densitometry. Pro-MMP-2 showed similar activity levels in dogs with idiopathic polyarthritis (IPA; n=17) or canine rheumatoid arthritis (cRA; n=4), and healthy controls (n=10). However, dogs with cranial cruciate ligament rupture (CCLR; n=5) presented significantly higher pro-MMP-2 activity than IPA and healthy dogs. Meanwhile, dogs with IPA exhibited significantly higher activity of pro- and active MMP-9 than other groups. Activity levels in pro- and active MMP-9 in cRA and CCLR dogs were not significantly different from those in healthy controls. Different patterns of MMP-2 and MMP-9 activity may reflect the differences in the underlying pathological processes. PMID- 26902806 TI - Effects of peripherally administered urotensin II and arginine vasotocin on the QT interval of the electrocardiogram in trout. AB - The QT interval of the electrocardiogram (ECG) is a measure of the duration of the ventricular depolarization and repolarization. In fish as in human, the QT interval is positively correlated with the RR interval of the ECG, a measure of the cardiac cycle length. Urotensin II (UII) is a neuropeptide that has been highly conserved from fish to human, and UII and its receptor (UT) are expressed in cardiovascular tissues including the heart. Although UII exerts potent cardiovascular actions, its possible effects on the QT interval have never been investigated. The goal of the present study was to provide insight into the potential effect of UII on the QT interval in an established in vivo trout model. To this end, the effects of UII on dorsal aortic blood pressure (PDA), RR, QT intervals and corrected QT (QTc) for RR interval, were investigated after intra arterial (IA) injection of 5, 50 and 100 pmol UII. The effects of UII were compared to those of two structurally UII-related peptides (URPs), URP1 and URP2, and to those of arginine vasotocin (AVT), homolog of the mammalian arginine vasopressin. IA injection of vehicle or 5 pmol UII had no effect on the various parameters. At the 50-pmol dose, UII evoked its usual increase in PDA with a peak value observed 15 min after the injection (+22% from baseline, P<0.001). This hypertensive effect of UII was accompanied by a significant increase in the RR interval (+18%, P<0.001), i.e. a bradycardia, and these effects remained constant until the end of the recording. The highest dose of UII evoked similar hypertensive and bradycardic effects. Of interest, the QT interval did not change during the bradycardic action of UII (50 and 100 pmol) but the QTc interval significantly decreased. In trout pre-treated with urantide, a peptidic antagonist of UT, the hypertensive and bradycardic actions of 50 pmol UII were reduced 3-fold and no change occurred in the QT and QTc intervals. In trout pre treated with blockers of the autonomic nervous system, the hypertensive effect of UII was maintained but no change appeared in RR, QT and QTc intervals. IA injections of 50 pmol URPs were without action on the preceding parameters. IA administration of 50 pmol AVT provoked quite similar increase in PDA, and elevation of the RR interval to those evoked by IA injection of UII but, in contrast to UII, AVT injection induced a highly significant and sustained prolongation of the QT interval compared to baseline (+7%, P<0.001) without change in QTc. Our results are indicative of a lack of QT interval change during UII-evoked bradycardia but not after AVT-induced bradycardia and suggest for the first time that some compensatory mechanism specific for the UII peptide is working to stabilize the QT interval. Further research is needed to elucidate the mechanism involved in this action of UII. The potential for UII to prevent detrimental prolongation of cardiac ventricular repolarization might be questioned. PMID- 26902809 TI - Enhancing Routine Immunization Performance using Innovative Technology in an Urban Area of Nigeria. AB - BACKGROUND: Routine Immunization (RI)is known to beone of the most cost-effective public health strategies ever, and a cornerstone among all primary healthcare efforts but has been bedevilledin Low and Middle Income Countries (LMICs) in the last two decadesby poor coverage and lack of timeliness -both due, among other factors, to clients forgetting appointments. These setback RI effectiveness from ensuring herd immunity and preventing disease. Across the world, different cost effective mobile telephone-based reminder systems are currently in use as strategies for improving coverage and compliance in various health interventions.Their application to RI is thereforehighly recommended. OBJECTIVE: This study sought to provide evidence validating the need for development and deployment of automated client Reminder-Recall systems for the Nigerian National Routine Immunisation Program and to compare its projected cost withthe cost of a health personnel-based defaulter tracking system. METHODOLOGY: A multi-centre, parallel-group, Randomized Controlled Trial was carried outusing multi-stage sampling.Nine hundred and five child-caregivers were followed-upat 8 health facilities in an urban/sub-urban area in South-South Nigeria.Text messagereminders were sent to the Intervention group only, with concurrent weekly data collection, including that for controls, at each of the enrolled health facilities. Recall messages were sent to defaulters and their responses (presence at immunization session) assessed the next RI session. Receipt of DPT3 vaccine on or before the 18th week was categorized early, while receiptafter was categorized delayed. RESULTS: Clients in the Interventiongroup were1.5times earlier than Controls intheir receipt of DPT3. Immunization coverage was also 8.7%better in the Interventiongroup. A first year estimate of cost of deploying this strategy was less than a quarter ofthe estimated cost of using home-visits which is the defaulter tracking method currently recommended by regulatory authorities. CONCLUSION: Routine immunization performance was significantly better in the Interventiongroup who received SMS reminders compared to the controls who did not. Since this occurred at a cheaper rate than projected costs of home visits, in a habitual stock-out situation, this is ample evidence for health policy makers in LMICs to leverage the ever expanding mobile telecom platforms for future sustainable improvements in routine immunisation performance and even other disease control efforts in Nigeria. PMID- 26902808 TI - A vital role for myosin-9 in puromycin aminonucleoside-induced podocyte injury by affecting actin cytoskeleton. AB - Podocyte injury is an early pathological change of many kidney diseases. In particular, the actin cytoskeleton plays an important role in maintaining the normal function of podocytes. Disruption of the actin cytoskeleton is a feature of podocyte injury in proteinuric nephropathies. Recent studies showed that myosin-9 was localized in the podocyte foot processes and was necessary in maintaining podocyte structural homeostasis. However, it is unclear whether myosin-9 maintains podocyte structure by affecting actin cytoskleton. Here, the role of myosin-9 in puromycin aminonucleoside (PAN)-induced podocyte injury was explored both in vitro and in vivo. In cultured mouse podocytes (MPC5), it was determined that PAN downregulated myosin-9 expression, disrupted the actin cytoskeleton and reduced the adhesion ability. Reduced myosin-9 expression by siRNA precipitated podocyte cytoskeletal damage and accelerated PAN-induced podocyte detachment. Overexpression of myosin-9 protected against PAN-induced podocyte detachment. Furthermore, administration of an antioxidant Mn(III)tetrakis (4-benzoic acid) porphyrin (MnTBAP) inhibited PAN-induced podocyte cytoskeletal damage and podocyte detachment by restoring the expression of myosin-9. In the rat PAN nephropathy model, MnTBAP could also attenuate PAN induced reduction of myosin-9 and podocyte loss. Taken together, these findings pinpointed that oxidative stress contributed to PAN-induced podocyte injury through the repression of a cytoskeletal protein myosin-9, which provided novel insights into a potential target for the treatment of podocyte injury-associated glomerulopathies. PMID- 26902810 TI - A Review of Total Hip Arthroplasty and Post-Operative Functional Hip Scores in National Orthopaedic Hospital,Lagos. AB - BACKGROUND: Hip pain that severely limits functional activity, and unresponsive to other measures of treatment is the major indication for Total Hip Arthroplasty. Hip scores are used to access functional outcome, by comparing pre operative and post-operative scores. STUDY DESIGN: The aim of this study was to investigate the overall functional outcome after Total hip Arthroplasty, and compare results between two approaches to the hip (Direct lateral and Posterior approach). A retrospective study of 56 total hip arthroplasty between January 2011 and September 2013. Pre-operative and Post-operative functional hip scores were assessed using the Harris Hip Score. Functional and clinical outcome of surgery was compared between two approaches to the hip. RESULTS: Approach to the hip was 61% for direct lateral and 39% for posterior approach. Superficial surgical site infection was recorded in 10 cases, 7 of these were in patients who had direct lateral approach. Post-operative HIP Score was excellent in 41%, and good in 52% of cases with a mean assessment at 6 weeks. CONCLUSION: The post operative functional status, measured by the Harris Hip score, was satisfactory in over 90% of cases. There was no statistically significant difference in Harris Hip Scores in the two approaches (p>0.05). PMID- 26902811 TI - Factors Associated with Missed Immunization Opportunities in Abakaliki, South Eastern Nigeria. AB - OBJECTIVE: To determined the extent and sociodemographic factors associated with missed opportunities to NPI-scheduled childhood immunizations Methods: The exit interview method of the World Health Organization was used. RESULTS: Only 41.6% of the children were fully immunized. Missed opportunities for immunization occurred in 277 (55.4%) children and were responsible for 94.9% of the non-fully immunized children. The most common reason for missed opportunities in this study was the unavailability of vaccines (78.3%). Missed opportunities occurred more in the age group of 0-11 months (92.4%) compared to those aged 12-23 months (7.6%), P<0.05. The social class of the parents was statistically significant in predicting the likelihood of missed opportunities in this study (P< 0.05). CONCLUSION: Missed opportunities to immunization (MO) remained high in EBSUTH, Abakaliki because immunization is conducted once a week in the preventive department only.MO is more common among children whose parents were in the lower social class. PMID- 26902807 TI - Regulation of the clock gene expression in human adipose tissue by weight loss. AB - BACKGROUND: The circadian clock coordinates numerous metabolic processes to adapt physiological responses to light-dark and feeding regimens and is itself regulated by metabolic cues. The implication of the circadian clock in the regulation of energy balance and body weight is widely studied in rodents but not in humans. Here we investigated (1) whether the expression of clock genes in human adipose tissue is changed by weight loss and (2) whether these alterations are associated with metabolic parameters. SUBJECTS/METHODS: Subcutaneous adipose tissue (SAT) samples were collected before and after 8 weeks of weight loss on an 800 kcal per day hypocaloric diet (plus 200 g per day vegetables) at the same time of the day. Fifty overweight subjects who lost at least 8% weight after 8 weeks were selected for the study. The expression of 10 clock genes and key metabolic and inflammatory genes in adipose tissue was determined by quantitative real-time PCR. RESULTS: The expression of core clock genes PER2 and NR1D1 was increased after the weight loss. Correlations of PERIOD expression with body mass index (BMI) and serum total, high-density lipoprotein and low-density lipoprotein (LDL) cholesterol levels and of NR1D1 expression with total and LDL cholesterol were found that became non-significant after correction for multiple testing. Clock gene expression levels and their weight loss-induced changes tightly correlated with each other and with genes involved in fat metabolism (FASN, CPT1A, LPL, PPARG, PGC1A, ADIPOQ), energy metabolism (SIRT1), autophagy (LC3A, LC3B) and inflammatory response (NFKB1, NFKBIA, NLRP3, EMR1). CONCLUSION: Clock gene expression in human SAT is regulated by body weight changes and associated with BMI, serum cholesterol levels and the expression of metabolic and inflammatory genes. Our data confirm the tight crosstalk between molecular clock and metabolic and inflammatory pathways involved in adapting adipose tissue metabolism to changes of the energy intake in humans. PMID- 26902812 TI - The Role of Nutritional Status on Follow-up among HIV-infected Children at a Teaching Hospital Clinic in Ghana. AB - BACKGROUND: Malnutrition and HIV infection in children interact adversely and may have a combined effect on clinical outcomes, including response to antiretroviral treatment (ART). Evidence of the role of malnutrition at the point of registration at HIV clinics is limited. This study sought to determine the role of nutritional status and other clinical factors on loss to follow-up (LTFU) among children at Komfo Anokye Teaching Hospital Pediatric HIV clinic in Kumasi, Ghana. STUDY DESIGN: A total of 324 HIV-positive children aged 1.5 to 10 years old who were registered at the clinic from January 1, 2007 to June 30, 2011 were included in this retrospective study. Weight-for-age z-score (WAZ) was used to classify nutritional status. Characteristics of children who were LTFU and those who remained in care were compared using bivariate analysis and logistic regression. RESULTS: At registration, 116 (35.8%) children were severely underweight (WAZ < -3) and 72 (22.2%) were underweight (WAZ < -2). A total of 163 (50.3%) children were LTFU during the course of one year. Malnourished children compared to normal weight children (WAZ > -2) were more likely to be LTFU (P = 0.003). Initiation of antiretroviral therapy was associated with a lower risk of LTFU. In the multivariate analysis, hospital admission (OR 4.38; 95% CI 2.30, 8.34) and initiation of ART (OR 0.33; CI 0.19, 0.56) were independently associated with LTFU. CONCLUSION: Malnutrition was common among Ghanaian HIV infected children and appeared to be associated with a higher risk of hospitalization and LTFU. Irrespective of nutritional status, the initiation of ART was associated with better retention in care. PMID- 26902813 TI - Sensorineural Hearing Loss and Dyslipidemia: Is There Any Relationship? AB - BACKGROUND: The incidence of dyslipidemia is increasing worldwide due to changes in diet and lifestyle. The aetiological role of dyslipidemia in sensorineural hearing loss (SNHL) is unclear. OBJECTIVE: To determine the association between SNHL and dyslipidemia in adult Nigerian population. DESIGN OF THE STUDY: This prospective case control study was carried out at ENT Department of University College Hospital Ibadan from August 2013 to May 2014. METHODS: The study involved consecutive adult patients (18-60 years) with SNHL. The controls were adults without SNHL matched for age, gender and socioeconomic status. Relevant clinical data were obtained. Hearing threshold was determined by standard method and fasting plasma lipid assayed for triglycerides (TG), total cholesterol (TC), high density and lipoprotein-cholesterol (HDL-C). The low density lipoprotein cholesterol (LDL-C) was calculated from TG, TC and HDL-C using Freidewald's formulae. The values of <40mg/dl, >200mg/dl, >150mg/dl and >130mg/dl were considered abnormal for HDL-C, TC, TG and LDL-C respectively. Level of statistical significance was P<0.05. RESULTS: There were 108 participants, consisting 57 (67.7%) cases and 51 (32.9%) controls with mean age of 37.911.3 years and 37.4 11.3-year respectively (p=0.708). Abnormalities in HDL-C values was the commonly observed in both cases (64.9%) and controls (76.5%).Thirty-six (63.2%) cases had severe to profound hearing loss. There was no significant correlation between lipid parameters and severity of SNHL. CONCLUSION: The prevalence of dyslipidemia in adult patients with sensorineural hearing loss is similar to those with normal hearing. There appears to beno causal association between dyslipidemia and sensorineural hearing loss. PMID- 26902815 TI - Aetiology and Precipitants of Epileptic Seizures among Nigerians Treated at Two Tertiary Hospitals in Kaduna State, Northern Nigeria. AB - BACKGROUND: Epilepsy is a common neurological illness in Nigeria with a prevalence of 5-37 per 1000 in a rural population. Several studies suggest that the prevalence of epilepsy is higher in developing than developed countries due to the preponderance of more risk factors in the former. This study investigated the aetiological factors and precipitants of epileptic seizures among patients attending outpatient clinics of two tertiary hospitals in Kaduna State, Northern Nigeria from October 2008 to April 2013. PATIENTS AND METHODS: Two hundred and forty two consecutive adult patients with history of at least 2 unprovoked afebrile seizures were investigated for seizure patterns, aetiological and precipitating factors through history, physical examinations, laboratory tests and electroencephalography. RESULTS: The male to female ratio of study population was 3 (69%): 1(31%), with respective mean ages of 29.5+/-12.4and 30.7 +/- 16.0years. Their respective mean ages of onset of first seizures were 18.6 +/ 14.0and 20.9 +/-17.4 years. 88% of seizures were of focal origin (complex partial, 80%; simple partial, 8%). Although the causes and precipitants were unknown in 41% and 68% of cases respectively; head injury, neonatal asphyxia and psychoactive substance abuse were prominent aetiological factors. CONCLUSION: Although majority of epileptic seizures in Kaduna State, Northern Nigeria were of focal origin, majority of causes and precipitants remained largely unknown. PMID- 26902814 TI - A Preliminary Assessment of the Impact of a Continuing Medical Education Program on the Knowledge of Nigerian Pulmonologists Regarding the Management of Chronic Obstructive Pulmonary Disease. AB - BACKGROUND: The knowledge ofPulmonologists in Nigeria regarding the management of chronic obstructive pulmonary disease (COPD) is modest and needs to be improved. Continuing Medical education programs have the potential to improve the knowledge of doctors. OBJECTIVES: To determine the impact of attendance at a COPDtraining on the level of knowledge of pulmonologists in Nigeria. METHODS: A Cross sectional study conducted during the Nigerian Thoracic Society (NTS) annual conference held at Ile-Ife, Nigeria in November 2013. The participants included residents in respiratory medicine and qualified pulmonologists. The study instruments were pre-test and post-test questionnaires which comprised of the same set of questions. The pre-test was administered and retrieved before the start of the COPD symposium and the post-test immediately afterwards. The scores on the pre-test were compared with the scores on the post-test. RESULTS: There were 54pre-test and 46 post-test questionnaires. The maximum obtainable score was 25. The mean score+/-standard deviation on the pre-test was 13+/-6 and 17+/-5 on post-test (t=-3.9, p<0.001) translating to an improvement in knowledge from 52% to 68%. Assessment of airflow limitation using spirometry in the initial evaluation for COPD was correctly selected by 57.4% on pre-test and 65.2% on post test (p=0.42). The knowledge of tuberculosis and environmental pollution were the least recognized risk factors for COPD and mood/anxiety disorder was the least recognized comorbid condition. CONCLUSION: The level of knowledge of pulmonologists in Nigeria about COPD is modest and participation at a CME program improved their knowledge. PMID- 26902816 TI - Minimal Access Surgery Educational Needs of Trainees from Africa: Perspectives from an Asian Training Institution. AB - BACKGROUND: The establishment of minimal access surgery (MAS) in the last three decades brought new dimensions to surgical training. The sole role of traditional apprenticeship training model was challenged and adjunctive surgical simulation models were introduced. Knowledge of the trainees' educational needs is important in designing MAS training curriculum. OBJECTIVES: To study the MAS educational needs of trainees from Africa, review MAS training models and offer recommendations for MAS training. METHODOLOGY: Data was obtained from questionnaires filled by trainees from Africa who attended the monthly MAS training at the World Laparoscopy Hospital, India from October 2013 to May 2014 about their MAS educational needs. RESULTS: There were 38 trainees from different parts of Africa (Central, East, North, South and West Africa) with average age of 41.92 +/- 8.67 years (minimum-28 years and maximum 63 years) and majority were males (92%). General surgeons constituted 57% while Gynaecologists were 41%. Only a quarter have MAS training integrated in their training curriculum. Box trainers, Animal models, live human surgeries and virtual reality simulation were the commonest models used in previous trainings and favoured in the educational needs for MAS training. Using cadaveric models and self sponsorship were deemphasised. CONCLUSION: Widespread application of MAS, globalisation and trainees educational needs call for establishing training programmes. Box trainers, animal models, live human surgeries and virtual reality simulators should be adopted and a synergy between Postgraduate surgical programmes, biomedical industry, universities and trainees will facilitate the setting of MAS skills laboratories and programmes. PMID- 26902817 TI - Outcome of Extremely Low Birth Weight Babies in Zaria; A Ten-Year Review. AB - BACKGROUND: Survival among extremely low birth weight (ELBW) babies (birth weight below 1000grams) in resource limited settings is still very low. The study aimed to determine the correlation between materno-foetal factors and outcome in this category of neonates. STUDY DESIGN: A retrospective study in which patients' records admitted into the Neonatal Unit of Ahmadu Bello University Teaching Hospital between January 2005 and December 2014 were retrieved. Information on neonates weighing < 1000 g were extracted and analyzed. Survival at discharge was the primary outcome. RESULTS: The overall survival rate of extremely low birth weight babies was 18%. Mortality in ELBW neonates weighing less than 750g was 100%. Factors that were significantly predictive of survival were birth weight, parity and duration of hospital stay with p-values of 0.014, 0.039 and 0.025 respectively CONCLUSION: The survival rate of ELBW babies remains low in our resource constrained setting. Focus should be on preventing preterm deliveries and as well equipping newborn care providers and newborn units with the necessary skills and materials respectively to enable implementation of evidence based interventions to improve newborn survival. PMID- 26902818 TI - Febrile Illness and Intravenous Antimalarial Treatment at a District Hospital in Cameroon. AB - BACKGROUND: Malaria is one of the most common causes of mortality worldwide. The World Health Organization (WHO) has recently recommended that treatment should be guided by a laboratory diagnosis. The aim of this study is to explore patient and health care factors associated with intravenous antimalarial treatment of malaria test-negative patients at a district hospital in a malaria endemic area. STUDY DESIGN: A cross-sectional study of 91 patients admitted for intravenous antimalarial treatment was done at a district hospital in northern Cameroon in July and August 2010. Socio-cultural and clinical factors were studied in relation to quality blood smear results. RESULTS: Thirty-two per cent of all intravenous antimalarials were administered to patients with a negative malaria test. Test negative patients older than 40 years of age received significantly more often intravenous antimalarials than the youngest patients (OR = 7.9, 95% CI = 1.9-32.4, p = 0.004). Few differential diagnoses were identified in the study population, and patients older than 30 years of age had malaria less often than the youngest patients (OR = 0.3, 95% CI = 0.08-0.9 and OR = 0.09, 95% CI = 0.02 0.4). CONCLUSION: This study supports previous reports of over-diagnosis and treatment of malaria in endemic areas. The results suggest that differential diagnoses are important, especially in adults with febrile illnesses to ensure the correct diagnosis and treatment. Further studies are needed to explore the findings and to develop strategies to improve the management of malaria and its differential diagnoses. PMID- 26902819 TI - Drain Site Hernia: A Review of the Incidence and Prevalence. AB - BACKGROUND: Surgical drains prevent fluid accumulation such as peritoneal fluid, blood, pus or inflammatory exudates. However, complications may occur. The aim of this study is to review the incidence and prevalence of drain site hernia as a complication of surgical drains. MATERIAL AND METHODS: A search of the literature in the MEDLINE database, using PubMed and OvidSP, Scopus, Google Scholar and Cochrane Databases with the following MeSH terms: (Drain or surgical drain or drainage) AND (drain hernia, drain-site hernia, laparoscopic drain-site hernia)was done. Also, these searches done from 14th-31st Dec 2013 were restricted according to the following MeSH limits: (a) January 1, 1980 to December 14, 2013, (b) English articles (c) Human. RESULTS: Overall, 24 articles had 49 patients with drain site hernias. Of this, 7 (14. 3 %) post open surgery while 42 (85.7 %) post laparoscopic surgery. Seven (14.3 %) occurred immediately after the operation/removal of drain, 10 (20.4 %) several days to 2 week, while 32 (65.3 %) several months to years. Commonest organ of herniation was 13 (26.5 %) small bowel, while morbidities, arising from drain site hernias occurred in 17 (34.7 %) with the highest 7 (14.3 %) due to bowel strangulation. Previous reports have quoted the incidence of drain site hernia to be 3.4% (5 of 148), and 0.14% (8 of 5541). Mortality was extremely low (2.0 %). CONCLUSION: Attention is warranted for drain site hernias as a significant complication following placement of surgical drain. Incidence (0.1-3.4 %), though wide range, is quite significant in these patients. Therefore, unwanted surgical drain insertion should be avoided. PMID- 26902820 TI - Cerebral Venous Thromboses in a Child with Nephrotic Syndrome. AB - Nephrotic syndrome is associated with several complications among which are thrombo embolic phenomena. These are uncommon in children. This report describes an 8 year old male child with relapse of steroid resistant minimal change nephrotic syndrome who developed cerebral sagittal and transverse sinus thromboses. He presented with headaches, vomiting and photophobia; and developed VI cranial nerve palsy during the course of the illness. Diagnosis was made by Computed Tomographic Scan and Magnetic Resonance Angiography of the brain. He was treated with low molecular weight heparin initially and then, oral warfarin with close monitoring of the INR and anti-Factor Xa. He recovered without neurological deficits from the venous thromboses, and with marked improvements in his radiological features. PMID- 26902821 TI - Brain correlates of phonological recoding of visual symbols. AB - Learning to read involves setting up associations between meaningless visual inputs (V) and their phonological representations (P). Here, we recorded the brain signals (ERPs and fMRI) associated with phonological recoding (i.e., V-P conversion processes) in an artificial learning situation in which participants had to learn the associations between 24 unknown visual symbols (Japanese Katakana characters) and 24 arbitrary monosyllabic names. During the learning phase on Day 1, the strength of V-P associations was manipulated by varying the proportion of correct and erroneous associations displayed during a two alternative forced choice task. Recording event related potentials (ERPs) during the learning phase allowed us to track changes in the processing of these visual symbols as a function of the strength of V-P associations. We found that, at the end of the learning phase, ERPs were linearly affected by the strength of V-P associations in a time-window starting around 200ms post-stimulus onset on right occipital sites and ending around 345ms on left occipital sites. On Day 2, participants had to perform a matching task during an fMRI session and the strength of these V-P associations was again used as a probe for identifying brain regions related to phonological recoding. Crucially, we found that the left fusiform gyrus was gradually affected by the strength of V-P associations suggesting that this region is involved in the brain network supporting phonological recoding processes. PMID- 26902823 TI - Acute Posterior Multifocal Placoid Pigment Epitheliopathy Following Dengue Fever: A New Association for an Old Disease. AB - PURPOSE: An association between antecedent viral illness and acute posterior multifocal placoid pigment epitheliopathy (APMPPE) has long been suspected. The authors propose dengue fever as a possible cause of APMPPE, based on three patients who travelled to or lived in endemic areas and had serologic evidence of prior exposure. METHODS: Review of case records of two patients. RESULTS: The index patient presented with APMPPE after her second confirmed dengue infection. A second patient with positive serology for dengue was subsequently identified, who had acute onset of posterior uveitis with APMPPE-like features. Dengue antibody titers were positive in both patients. CONCLUSIONS: APMPPE may be another manifestation of dengue fever. Ophthalmologists should take travel histories and consider ordering dengue serology in appropriate patients with APMPPE even if fever is absent, and especially in patients with the possibility of attenuated systemic disease and a primarily immunologic reaction to subsequent exposure. PMID- 26902822 TI - Real-time bacterial microcolony counting using on-chip microscopy. AB - Observing microbial colonies is the standard method for determining the microbe titer and investigating the behaviors of microbes. Here, we report an automated, real-time bacterial microcolony-counting system implemented on a wide field-of view (FOV), on-chip microscopy platform, termed ePetri. Using sub-pixel sweeping microscopy (SPSM) with a super-resolution algorithm, this system offers the ability to dynamically track individual bacterial microcolonies over a wide FOV of 5.7 mm * 4.3 mm without requiring a moving stage or lens. As a demonstration, we obtained high-resolution time-series images of S. epidermidis at 20-min intervals. We implemented an image-processing algorithm to analyze the spatiotemporal distribution of microcolonies, the development of which could be observed from a single bacterial cell. Test bacterial colonies with a minimum diameter of 20 MUm could be enumerated within 6 h. We showed that our approach not only provides results that are comparable to conventional colony-counting assays but also can be used to monitor the dynamics of colony formation and growth. This microcolony-counting system using on-chip microscopy represents a new platform that substantially reduces the detection time for bacterial colony counting. It uses chip-scale image acquisition and is a simple and compact solution for the automation of colony-counting assays and microbe behavior analysis with applications in antibacterial drug discovery. PMID- 26902824 TI - A highly efficient degradation mechanism of methyl orange using Fe-based metallic glass powders. AB - A new Fe-based metallic glass with composition Fe76B12Si9Y3 (at. %) is found to have extraordinary degradation efficiency towards methyl orange (MO, C14H14N3SO3) in strong acidic and near neutral environments compared to crystalline zero valent iron (ZVI) powders and other Fe-based metallic glasses. The influence of temperature (294-328 K) on the degradation reaction rate was measured using ball milled metallic glass powders revealing a low thermal activation energy barrier of 22.6 kJ/mol. The excellent properties are mainly attributed to the heterogeneous structure consisting of local Fe-rich and Fe-poor atomic clusters, rather than the large specific surface and strong residual stress in the powders. The metallic glass powders can sustain almost unchanged degradation efficiency after 13 cycles at room temperature, while a drop in degradation efficiency with further cycles is attributed to visible surface oxidation. Triple quadrupole mass spectrometry analysis conducted during the reaction was used to elucidate the underlying degradation mechanism. The present findings may provide a new, highly efficient and low cost commercial method for azo dye wastewater treatment. PMID- 26902825 TI - Flow invariant droplet formation for stable parallel microreactors. AB - The translation of batch chemistries onto continuous flow platforms requires addressing the issues of consistent fluidic behaviour, channel fouling and high throughput processing. Droplet microfluidic technologies reduce channel fouling and provide an improved level of control over heat and mass transfer to control reaction kinetics. However, in conventional geometries, the droplet size is sensitive to changes in flow rates. Here we report a three-dimensional droplet generating device that exhibits flow invariant behaviour and is robust to fluctuations in flow rate. In addition, the droplet generator is capable of producing droplet volumes spanning four orders of magnitude. We apply this device in a parallel network to synthesize platinum nanoparticles using an ionic liquid solvent, demonstrate reproducible synthesis after recycling the ionic liquid, and double the reaction yield compared with an analogous batch synthesis. PMID- 26902828 TI - Osimertinib Western and Asian clinical pharmacokinetics in patients and healthy volunteers: implications for formulation, dose, and dosing frequency in pivotal clinical studies. AB - PURPOSE: Osimertinib (AZD9291) 80 mg once daily is approved by the US FDA for the treatment of patients with metastatic EGFR T790M-positive NSCLC whose disease has previously progressed on EGFR-TKI therapy. Osimertinib PK was evaluated to define the dose and dosing interval, whether a fixed-dosing approach can be used globally, and the impact of formulation and food on exposure. METHODS: AURA (NCT01802632): single- and multiple-dose PK of osimertinib (20-240 mg daily) was determined in patients with advanced NSCLC. Bioavailability study (NCT01951599): single-dose PK of osimertinib (20 mg) was determined in healthy volunteers with administration of capsule, solution, or tablet formulations fasted, and as a tablet in the fed and fasted state. RESULTS: Osimertinib was slowly absorbed and displayed dose-proportional increases in exposure from 20 to 240 mg. Distribution was extensive and clearance low to moderate, resulting in a mean half-life of 48.3 h. Steady state was achieved by 15 days of dosing, consistent with single dose PK, with a peak-to-trough ratio of 1.6. Two active metabolites circulated at ~10 % of osimertinib exposure. Ethnicity did not appear to affect exposure. Osimertinib PK profiles in healthy volunteers were similar to those in patients and were unaffected by formulation. Food caused a clinically insignificant increase in exposure. CONCLUSIONS: Osimertinib PK supports once-daily dosing; the same dose for Asian and non-Asian populations; a fixed-dosing approach; a minimal effect of food on exposure; and a switch to tablet formulation without alteration to dose or schedule. Osimertinib plasma concentrations are sustained throughout the dosing period, which is considered optimal for efficacy. PMID- 26902827 TI - TERT Promoter Mutations in Thyroid Cancer. AB - Two mutations (C228T and C250T) in the promoter region of the telomerase reverse transcriptase (TERT) have recently been described in different types of cancer including follicular cell-derived thyroid cancer (TC). In this paper, we reviewed the rates of these mutations in different types and subtypes of TC, their association with a number of clinical and histopathological features and outcome of TC, and their potential diagnostic and prognostic roles in TC. The overall rate of these mutations in TC is about 14 % with least prevalence in the well differentiated subtypes of papillary thyroid cancer (10-13 %). Their rates increase significantly with increasing aggressiveness of TC reaching about 40 % in the undifferentiated and anaplastic thyroid cancers. There is also clear association with increasing age of patients at the time of diagnosis of TC. The evidence is compelling but with some conflicting results for associations between TERT promoter mutations and tumor size, extrathyroidal invasion, distant metastases, high tumor TNM stage, BRAF (V600E) mutation, recurrence, and mortality. A couple of studies reported a potential diagnostic role for TERT promoter mutations in thyroid nodules with indeterminate cytology of fine needle aspiration biopsy. These studies showed 100 % specificity but very low sensitivity of 7-10 %. The sensitivity increases significantly when TERT promoter mutation testing is combined with other gene mutations, particularly BRAF (V600E) and RAS mutations. Although TERT promoter mutations seem to play significant roles in the pathogenesis of TC, the mechanisms by which they contribute to carcinogenesis remain elusive and future work is needed to fully assess the roles, interactions, and impact of these mutations on the pathogenesis, diagnosis, prognosis, and therapeutics of TC. PMID- 26902826 TI - Nipple Aspirate Fluid Hormone Concentrations and Breast Cancer Risk. AB - Prior reports identify higher serum concentrations of estrogens and androgens as risk factors for breast cancer, but steroids in nipple aspirate fluid (NAF) may be more related to risk. Incident breast cancer cases and mammography controls were recruited. Sex steroids were measured in NAF from the unaffected breasts of cases and one breast of controls. Menopausal status and menstrual cycle phase were determined. NAF steroids were purified by HPLC and quantified by immunoassays. Conditional logistic regression models were used to examine associations between NAF hormones and case-control status. NAF samples from 160 cases and 157 controls were evaluable for hormones. Except for progesterone and dehydroepiandrosterone (DHEA), the NAF and serum concentrations were not significantly correlated. NAF estradiol and estrone were not different between cases and controls. Higher NAF (but not serum) DHEA concentrations were associated with cases, particularly among estrogen receptor (ER)-positive cases (NAF odds ratio (OR) = 1.18, 95 % confidence interval (CI) 1.02, 1.36). NAF DHEA was highly correlated with NAF estradiol and estrone but not with androstenedione or testosterone. Higher progesterone concentrations in both NAF and serum were associated with a lower risk of ER-negative cancer (NAF OR = 0.69, 95 % CI 0.51, 0.92). However, this finding may be explained by case-control imbalance in the number of luteal phase subjects (2 cases and 19 controls). The significantly higher concentration of DHEA in NAF of cases and its correlation with NAF estradiol indicates a potentially important role of this steroid in breast cancer risk; however, the negative association of progesterone with risk is tentative. PMID- 26902829 TI - Kinetics of alpha-amylase and alpha-glucosidase inhibitory potential of Zea mays Linnaeus (Poaceae), Stigma maydis aqueous extract: An in vitro assessment. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Corn silk (Zea mays L., Stigma maydis) is an important herb used traditionally in many parts of the world to treat array of diseases including diabetes mellitus. Inhibitors of alpha-amylase and alpha glucosidase offer an effective strategy to modulate levels of post prandial hyperglycaemia via control of starch metabolism. AIM OF THE STUDY: This study evaluated alpha-amylase and alpha-glucosidase inhibitory potentials of corn silk aqueous extract. Active principles and antioxidant attributes of the extract were also analysed. MATERIALS AND METHODS: The alpha-amylase inhibitory potential of the extract was investigated by reacting its different concentrations with alpha amylase and starch solution, while alpha-glucosidase inhibition was determined by pre-incubating alpha-glucosidase with different concentrations of the extract followed by addition of p-nitrophenylglucopyranoside. The mode(s) of inhibition of the enzymes were determined using Lineweaver-Burke plot. RESULTS: In vitro analysis of the extract showed that it exhibited potent and moderate inhibitory potential against alpha-amylase and alpha-glucosidase, respectively. The inhibition was concentration-dependent with respective half-maximal inhibitory concentration (IC50) values of 5.89 and 0.93mg/mL. Phytochemical analyses revealed the presence of alkaloids, flavonoids, phenols, saponins, tannins and phytosterols as probable inhibitory constituents. Furthermore, the extract remarkably scavenges reactive oxygen species like DPPH and nitric oxide radicals, elicited good reducing power and a significant metal chelating attributes. CONCLUSION: Overall, the non-competitive and uncompetitive mechanism of action of corn silk extract is due to its inhibitory effects on alpha-amylase and alpha glucosidase, respectively. Consequently, this will reduce the rate of starch hydrolysis, enhance palliated glucose levels, and thus, lending credence to hypoglycaemic candidature of corn silk. PMID- 26902830 TI - Protective effect of Naoxintong against cerebral ischemia reperfusion injury in mice. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Naoxintong (NXT), a renowned traditional Chinese medicine in China, has been used for the treatment of acute and chronic cardio cerebrovascular diseases in clinic for more than 20 years. AIM OF THE STUDY: To evaluate the potential neuroprotective effect of NXT against ischemia reperfusion (I/R) injury in mice and investigate the underlying mechanisms. MATERIALS AND METHODS: Focal cerebral I/R injury in adult male CD-1 mice was induced by transient middle cerebral artery occlusion (tMCAO) for 1h followed by reperfusion for 23h. Mice were randomly divided into five groups: Sham group; tMCAO group; Vehicle group; NXT-treated groups at doses of 0.36g/kg and 0.54g/kg. The effects of NXT on murine neurological function were estimated by neurological defect scores, infarct volume and brain water content at 24h after tMCAO. Immunohistochemistry and Western blot were used to detect the expression of LOX 1, pERK1/2 and NF-kappaB at 24h after tMCAO. qRT-PCR was used to detect the expression of LOX-1 and NF-kappaB at 24h after tMCAO. RESULTS: Compared with Vehicle group, 0.54g/kg group of NXT significantly ameliorated neurological outcome, infarction volume and brain water content, decreased the expression of LOX-1, pERK1/2 and NF-kappaB (P<0.05). CONCLUSION: NXT protected the mice brain against I/R injury, and this protection maybe associated with the down-regulation of LOX-1, pERK1/2 and NF-kappaB expression. PMID- 26902832 TI - A randomized, double-blind, placebo-controlled trial of a traditional herbal formula, Yukmijihwang-tang in elderly subjects with xerostomia. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Yukmijihwang-tang (YMJ) is a typical herbal formula to treat Yin-deficiency (YD) syndrome by enriching the fluid-humor of the body. YMJ has been used to treat dry mouth symptoms for hundreds of years in traditional East Asian medicine. Xerostomia, a subjective oral dryness, is common in the elderly and results in impaired quality of life. Many conventional treatments for xerostomia provide only temporary symptom relief, and have side effects. The aim of this study is to investigate the efficacy and safety of YMJ for the treatment of xerostomia in the elderly. METHODS: This study was designed as a randomized, placebo-controlled, double-blinded, two center trial. Ninety-six subjects aged 60-80 years who had experienced xerostomia for at least 3 months and presented with score>40 on the visual analog scale (VAS) for subjective oral dryness were recruited and randomly allocated to YMJ and placebo groups. YMJ or placebo was administered to each group for 8 weeks (3g of YMJ or placebo, three times per day). The primary outcome was change of VAS for xerostomia from 0 to 8 weeks. RESULTS: VAS for xerostomia was decreased by 22.04+/-22.76 in the YMJ group and 23.58+/-23.04 in the placebo group. YMJ had no effect on xerostomia. However, participants with BMIs lower than 29.37kg/m(2) showed improvement of xerostomia after 8 weeks of treatment with YMJ compared to placebo. In addition, YMJ improved oral moisture, which is associated with subjective oral dryness in the YMJ group, and the relationship between VAS for xerostomia and YD was significant. CONCLUSION: A trend was observed in which YMJ improved oral moisture status and subjective oral dryness in elderly subjects with lower BMI and greater tendency toward YD. PMID- 26902831 TI - Xylopia aethiopica fruit extract exhibits antidepressant-like effect via interaction with serotonergic neurotransmission in mice. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Xylopia aethiopica has been used traditionally to treat some central nervous system disorders including epilepsy. AIM OF THE STUDY: Despite the central analgesic and sedative effects, there is little evidence for its traditional use for CNS disorders. This study thus assessed the antidepressant potential of Xylopia aethiopica ethanolic fruit extract (XAE). MATERIAL AND METHODS: Antidepressant effect was assessed in the forced swim test (FST) and tail suspension test (TST) models in mice. The role of monoamines in the antidepressant effects of XAE was evaluated by selective depletion of serotonin and noradrenaline, whereas involvement of NMDA/nitric oxide was assessed with NMDA receptor co-modulators; d-serine and d-cycloserine and NOS inhibitor, l-NAME. RESULTS: Xylopia aethiopica (30, 100, 300mgkg(-1)) dose dependently reduced immobility in both FST and TST. The reduced immobility was reversed after 5-hydroxytryptamine (5-HT) depletion with tryptophan hydroxylase inhibitor-p-chlorophenylalanine (pCPA) and after monoamine depletion with vesicular monoamine transporter inhibitor-reserpine. The observed antidepressant effect was not affected by catecholamine depletion with the tyrosine hydroxylase inhibitor, alpha-methyl-p-tyrosine (AMPT). Similarly XAE did not potentiate the toxicity of a sub-lethal dose of noradrenaline. XAE had a synergistic effect with the glycineB receptor partial agonist, d-cycloserine and nitric oxide synthase inhibitor, l-NAME. However established antidepressant effects of XAE were abolished by NMDA and NOS activation with d-serine and l-arginine. CONCLUSION: This study shows that Xylopia aethiopica has antidepressant potential largely due to effects on 5-HT neurotransmission with possible glutamatergic effect through the glycineB co-binding site and nitric oxide synthase inhibition. PMID- 26902833 TI - Modeling Cryotherapy Ice Ball Dimensions and Isotherms in a Novel Gel-based Model to Determine Optimal Cryo-needle Configurations and Settings for Potential Use in Clinical Practice. AB - OBJECTIVE: To gain a better understanding of ice ball dimensions and temperature isotherms relevant for cell kill when using combinations of cryo-needles we set out to answer 4 questions: (1) what type of cryo-needle? (2) how many needles? (3) best spatial configuration? and (4) correct duty cycle percentage? METHODS: We conducted laboratory experiments to monitor ice ball dimensions and create multi-needle planar isotherm maps for 17G and 10G cryo-needles using a novel multi-needle thermocouple fixture within gel at body temperature. We tested configurations of 1-4 cryo-needles at duty cycles of 20%-100% with 1-2.5 cm spacing. RESULTS: Analysis of various combinations shows that a central core of <=-40 degrees C develops at a distance of ~1 cm around the cryo-needles. Temperature increases linearly from this point to the ice ball leading edge (0 degrees C), which is a further ~1 cm away. Thus, the -40 degrees C isotherm is approximately 1 cm inside the leading edge of the ice ball. The optimum distance between cryo-needles was 1.5-2 cm, at duty cycle settings of 70%-100%. At distances further apart or with lower duty cycle settings, ice balls either had a central core >-40 degrees C or had an hourglass shape. CONCLUSION: In answer to questions 1-3, tumor length, diameter, and shape will ultimately determine the number of needles and their configuration. However, we propose a conservative distance for cryo-needle placement between 1 and 1.5 cm should be adopted for clinical practice. In answer to question 4, using low duty cycle settings runs the risk of incomplete -40 degrees C isotherm coverage of the tumor, and thus in routine practice we suggest that settings of 70%-100% are most appropriate. PMID- 26902834 TI - Unusual Case of Voiding Symptoms and Constipation: Retrorectal Cystic Hamartoma. AB - Retrorectal cystic hamartoma (tailgut cyst) is a rare congenital lesion. This study is one of the few reports of this rare clinical entity causing irritative voiding symptoms and constipation in a male patient. Although most cases are asymptomatic, patients may present with symptoms resulting from local mass effect or complication. PMID- 26902835 TI - Clathrochelates meet phosphorus. New thio- and phosphorylation reactions of an iron(II) dichloroclathrochelate precursor and preparation of its first phosphorus(III)-containing macrobicyclic derivative. AB - Phosphorylation reactions of an iron(II) dichloroclathrochelate FeBd2(Cl2Gm)(BF)2 (where Bd(2-) and Cl2Gm(2-) are alpha-benzildioxime and dichloroglyoxime dianions, respectively) with diphenylphosphine oxide and diethyl thiophosphite were performed under phase-transfer conditions. In the case of diethyl thiophosphite as a P-nucleophile, the best yields were obtained in the dichloromethane-50% NaOH aqueous solution-5 mol% triethylbenzylammonium chloride (TEBAC) system. The use of different molar ratios of a macrobicycle precursor and this thiophosphorylating agent allowed us to obtain both the mono- and the diphosphorylated cage complexes. Nucleophilic substitution with diphenylphosphine oxide was performed in the K2CO3-acetonitrile-5 mol% TEBAC system, giving only the corresponding monophosphorylated iron(II) complex in high yield even in the presence of an excess of this P-nucleophile. The phosphorus(v)-containing clathrochelate product was reduced with an excess of silicoform to give an iron(II) macrobicycle with an inherent diphenylphosphine group in an almost quantitative yield, which was then characterized by (31)P{(1)H} NMR and single crystal X-ray diffraction; it easily undergoes re-oxidation to the initial clathrochelate. The synthesized phosphorus(v)-containing cage complexes were characterized using elemental analysis, MALDI-TOF mass, IR, UV-Vis, (1)H, (11)B, (13)C{(1)H}, (19)F{(1)H} and (31)P{(1)H} NMR spectra, and by single-crystal X-ray diffraction. PMID- 26902836 TI - Highly Selective Fluorescent Turn-On Probe for Protein Thiols in Biotin Receptor Positive Cancer Cells. AB - Sulfhydryl-containing proteins play critical roles in various physiological and biological processes, and the activities of those proteins have been reported to be susceptible to thiol oxidation. Therefore, the development of protein thiol target fluorescent probe is highly desirable. In the present work, a biotinylated coumarin fluorescence "off-on" probe SQ for selectively detecting protein thiols in biotin receptor-positive cancer cells was designed with a 2,4 dinitrobenzenesulfony as the thiol receptor. The probe exhibited dramatic fluorescence responses toward sulfhydryl-containing proteins (ovalbumin (OVA), bovine serum albumin (BSA)): up to 170-fold fluorescence enhancement with 70 nm blue-shift was observed with the addition of OVA. However, low molecular weight thiols (Cys, glutathione (GSH), Hcy) caused negligible fluorescence changes of SQ. In addition, biotin receptor-positive Hela cells displayed strong red and green fluorescence after incubation of SQ for 1 h; neither red nor green fluorescence signal could be visualized in biotin-negative normal lung Wi38 cells. These results imply that the probe has potential application in fluorescent imaging protein thiols on the surface of Hela cells. PMID- 26902838 TI - A synergetic application of surface plasmon and field effect to improve Si solar cell performance. AB - We report a synergetic application of surface plasmon (SP) and field effect (FE) to improve crystalline Si solar cell performance. The SPs are supported by small sized Ag nanoparticles with an average diameter of 36.7 nm. The localized SP electromagnetic field from Ag nanoparticles excites extra electron-hole pairs at the surface region of the Si solar cell emitter, and meanwhile, the electron-hole pairs are detached by the electrostatic field that crosses the emitter surface. This synergism of SP and FE produces extra charges and enhances the Si solar cell efficiency. As compared to a Si solar cell applying SP and FE independently, a more than 10% efficiency enhancement is achieved by using them synergistically. PMID- 26902837 TI - Transcriptional identification and characterization of differentially expressed genes associated with embryogenesis in radish (Raphanus sativus L.). AB - Embryogenesis is an important component in the life cycle of most plant species. Due to the difficulty in embryo isolation, the global gene expression involved in plant embryogenesis, especially the early events following fertilization are largely unknown in radish. In this study, three cDNA libraries from ovules of radish before and after fertilization were sequenced using the Digital Gene Expression (DGE) tag profiling strategy. A total of 5,777 differentially expressed transcripts were detected based on pairwise comparison in the three libraries (0_DAP, 7_DAP and 15_DAP). Results from Gene Ontology (GO) and pathway enrichment analysis revealed that these differentially expressed genes (DEGs) were implicated in numerous life processes including embryo development and phytohormones biosynthesis. Notably, some genes encoding auxin response factor (ARF ), Leafy cotyledon1 (LEC1) and somatic embryogenesis receptor-like kinase (SERK ) known to be involved in radish embryogenesis were differentially expressed. The expression patterns of 30 genes including LEC1-2, AGL9, LRR, PKL and ARF8-1 were validated by qRT-PCR. Furthermore, the cooperation between miRNA and mRNA may play a pivotal role in the radish embryogenesis process. This is the first report on identification of DEGs profiles related to radish embryogenesis and seed development. These results could facilitate further dissection of the molecular mechanisms underlying embryogenesis and seed development in radish. PMID- 26902841 TI - Temperature effects on the electrohydrodynamic and electrokinetic behaviour of ion-selective nanochannels. AB - A non-isothermal formulation of the Poisson-Nernst-Planck with Navier-Stokes equations is used to study the influence of heating effects in the form of Joule heating and viscous dissipation and imposed temperature gradients on a microchannel/nanochannel system. The system is solved numerically under various cases in order to determine the influence of temperature-related effects on ion selectivity, flux and fluid flow profiles, as well as coupling between these phenomena. It is demonstrated that for a larger reservoir system, the effects of Joule heating and viscous dissipation only become relevant for higher salt concentrations and electric field strengths than are compatible with ion selectivity due to Debye layer overlap. More interestingly, it is shown that using different temperature reservoirs can have a strong influence on ion selectivity, as well as the induced electrohydrodynamic flows. PMID- 26902840 TI - An examination of the relationship between athlete leadership and cohesion using social network analysis. AB - Two studies investigated the structure of different athlete leadership networks and its relationship to cohesion using social network analysis. In Study 1, we examined the relationship between a general leadership quality network and task and social cohesion as measured by the Group Environment Questionnaire (GEQ). In Study 2, we investigated the leadership networks for four different athlete leadership roles (task, motivational, social and external) and their association with task and social cohesion networks. In Study 1, the results demonstrated that the general leadership quality network was positively related to task and social cohesion. The results from Study 2 indicated positive correlations between the four leadership networks and task and social cohesion networks. Further, the motivational leadership network emerged as the strongest predictor of the task cohesion network, while the social leadership network was the strongest predictor of the social cohesion network. The results complement a growing body of research indicating that athlete leadership has a positive association with cohesion. PMID- 26902839 TI - Succinyl-proteome profiling of a high taxol containing hybrid Taxus species (Taxus * media) revealed involvement of succinylation in multiple metabolic pathways. AB - Protein lysine succinylation, a ubiquitous protein post-translational modification among eukaryotic and prokaryotic cells, represents a vital regulator of various metabolic processes. However, little is known about its functions and cellular distribution in Taxus * media, which is a hybrid Taxus species containing a high content of taxol. In this study, LC-MS/MS was used to identify peptides enriched by immune-purification with high-efficiency succinyl-lysine antibody. A total of 193 succinylated proteins and 325 succinylation sites were identified. The bioinformatics analysis indicated that these succinylated proteins were involved in a wide range of cellular functions from metabolism to protein binding and showed diverse subcellular localizations. Furthermore, our findings suggested that lysine succinylation in Taxus * media involved a diverse array of metabolic processes and protein-protein interactions. Many enzymes involved in multiple metabolic pathways, such as glycolysis, pyruvate metabolism, the tricarboxylic acid cycle and carbon fixation, were identified as substrates for lysine succinylation, suggesting the presence of a common mechanism underlying the participation of succinylation in metabolic regulation. These results provide the first comprehensive view of the succinylome of Taxus * media and may catalyze future biological investigation of succinylation. PMID- 26902842 TI - Endoscopic appendectomy showing an intramucosal carcinoma. PMID- 26902844 TI - Indeterminate biliary stricture with suspicion for malignancy unmasked as eosinophilic cholangitis by cholangioscopy. PMID- 26902845 TI - Recurrent dysphagia in a patient with chronic lymphocytic esophagitis. PMID- 26902846 TI - Embedded fish bone in the stomach mimicking a submucosal tumor. PMID- 26902843 TI - Risk of recurrence of Barrett's esophagus after successful endoscopic therapy. AB - BACKGROUND AND AIMS: Previous estimates of incidence of intestinal metaplasia (IM) recurrence after achieving complete remission of IM (CRIM) through endoscopic therapy of Barrett's esophagus (BE) have varied widely. We performed a systematic review and meta-analysis of studies to estimate an accurate recurrence risk after CRIM. METHODS: We performed a systematic search of multiple literature databases through June 2015 to identify studies reporting long-term follow-up after achieving CRIM through endoscopic therapy. Pooled incidence rate (IR) of recurrent IM, dysplastic BE, and high-grade dysplasia (HGD)/esophageal adenocarcinoma (EAC) per person-year of follow-up after CRIM was estimated. Factors associated with recurrence were also assessed. RESULTS: We identified 41 studies that reported 795 cases of recurrence in 4443 patients over 10,427 patient-years of follow-up. This included 21 radiofrequency ablation studies that reported 603 cases of IM recurrence in 3186 patients over 5741 patient-years of follow-up. Pooled IRs of recurrent IM, dysplastic BE, and HGD/EAC after radiofrequency ablation were 9.5% (95% CI, 6.7-12.3), 2.0% (95% CI, 1.3-2.7), and 1.2% (95% CI, .8-1.6) per patient-year, respectively. When all endoscopic modalities were included, pooled IRs of recurrent IM, dysplastic BE, and HGD/EAC were 7.1% (95% CI, 5.6-8.6), 1.3% (95% CI, .8-1.7), and .8% (95% CI, .5-1.1) per patient-year, respectively. Substantial heterogeneity was noted. Increasing age and BE length were predictive of recurrence; 97% of recurrences were treated endoscopically. CONCLUSIONS: The incidence of recurrence after achieving CRIM through endoscopic therapy was substantial. A small minority of recurrences were dysplastic BE and HGD/EAC. Hence, continued surveillance after CRIM is imperative. Additional studies with long-term follow-up are needed. PMID- 26902847 TI - Metastatic melanoma of the gallbladder diagnosed by EUS-guided FNA. PMID- 26902848 TI - Malignant intraductal papillary mucinous neoplasm of the pancreas with gastric and duodenal fistulas. PMID- 26902849 TI - Inactivating MUTYH germline mutations in pediatric patients with high-grade midline gliomas. PMID- 26902850 TI - A randomized, placebo-controlled pilot trial of armodafinil for fatigue in patients with gliomas undergoing radiotherapy. AB - BACKGROUND: Fatigue is common among glioma patients undergoing radiotherapy (RT) and impacts quality of life (QOL). We evaluated whether armodafinil, a wakefulness-promoting medication, improves fatigue in glioma patients undergoing RT. METHODS: Eligibility criteria included age >=18 years, Karnofsky performance status >=60, and grade 2-4 glioma undergoing RT to a total dose of 50-60 Gy. Patients were randomized 1:1 to armodafinil or placebo for 8 weeks beginning within 10 days of starting RT. Fatigue and QOL were assessed at baseline, day 22, day 43, and day 56 with the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F), the Functional Assessment of Cancer Therapy - General (FACT G), the Brief Fatigue Inventory (BFI), and the Cancer Fatigue Scale (CFS). The primary aim was to detect a difference in the 42-day change in FACIT-F fatigue subscale between the 2 groups using a 2-sample Wilcoxon statistic. RESULTS: We enrolled 81 patients total (42 armodafinil and 39 placebo). Armodafinil did not significantly improve fatigue or QOL based on the 42-day change in FACIT-F fatigue subscale, FACT-G, CFS, or BFI. Further analysis suggests no difference between the arms even after accounting for the potential bias of missing data. Treatment was well tolerated with few grade 3 or 4 toxicities. CONCLUSIONS: While treatment was well-tolerated, an 8-week course of armodafinil did not improve fatigue or QOL in glioma patients undergoing RT in this pilot study. Further studies are needed to determine whether pharmacologic treatment improves fatigue in glioma patients undergoing RT. PMID- 26902853 TI - Chimpanzee research and conservation in Bossou and the Nimba Mountains: a long term international collaborative effort in West Africa. AB - The Nimba Mountains are a West African Natural World Heritage site located in the range of the Guineo-equatorial evergreen rainforest, renowned for its rich biodiversity with a high level of endemism. In 1976, Yukimaru Sugiyama from Kyoto University initiated the long-term study of chimpanzees at Bossou, a Guinean village situated 5 km from the northern foothills of Nimba. This Japanese initiative has provided key discoveries and insights on our closest living evolutionary relatives over the 40 past years, and has grown to become an international collaboration with a research focus extended to adjacent chimpanzee communities. The present paper describes a mid-term behavioral and ecological study on wild chimpanzees populating the southern slope of the Nimba Mountains, conducted in the framework of this collaborative project. It aimed to assess the status and ecological requirements of chimpanzees in order to formulate purpose built actions for their conservation. We estimated a density of 0.46 chimpanzee per km(2) using nest count methods from line transects. We used logistic and Poisson regressions to investigate basic ecological characteristics of chimpanzees in relation to habitat composition and structure, topography and seasonality. We performed an in-depth analysis of their nesting and feeding behaviors, and identified important components of their diet; we also recorded their year-round ranging patterns. Our findings highlight the importance of old secondary forest and high-altitude habitats for these chimpanzees. We discuss the results in the light of other studies from the perspective of the conservation of the species and its natural habitat. PMID- 26902854 TI - Perceived Social Support as a Determinant of Quality of Life Among Medical Students: 6-Month Follow-up Study. AB - OBJECTIVE: This longitudinal study aimed to identify the relevant factors related to quality of life (QoL) changes in medical students. METHODS: For this 6-month follow-up study, we enrolled 109 students from a Korean medical school. To assess students' QoL, we used the World Health Organization QoL scale. Possible determinants of student QoL included demographics, fatigue, and social support. A stepwise multivariate analysis identified factors associated with changes of student QoL. RESULTS: Among sources of support, the "friends" category was the main position affecting their overall QoL, and "significant other" had the strongest influence on psychological and social domains. The impact of support from friends on QoL was confirmed in the longitudinal analysis. Final regression models revealed that providing students with more social support and promoting fatigue reduction best improved medical student sense of well-being. CONCLUSION: Creating stronger student support programs to prevent social detachment and implementing strategies to reduce fatigue can improve QoL in medical students. PMID- 26902851 TI - A Phase II randomized study of galunisertib monotherapy or galunisertib plus lomustine compared with lomustine monotherapy in patients with recurrent glioblastoma. AB - BACKGROUND: The combination of galunisertib, a transforming growth factor (TGF) beta receptor (R)1 kinase inhibitor, and lomustine was found to have antitumor activity in murine models of glioblastoma. METHODS: Galunisertib (300 mg/day) was given orally 14 days on/14 days off (intermittent dosing). Lomustine was given as approved. Patients were randomized in a 2:1:1 ratio to galunisertib + lomustine, galunisertib monotherapy, or placebo + lomustine. The primary objective was overall survival (OS); secondary objectives were safety, pharmacokinetics (PKs), and antitumor activity. RESULTS: One hundred fifty-eight patients were randomized: galunisertib + lomustine (N = 79), galunisertib (N = 39), and placebo + lomustine (N = 40). Baseline characteristics were: male (64.6%), white (75.3%), median age 58 years, ECOG performance status (PS) 1 (63.3%), and primary glioblastoma (93.7%). The PKs of galunisertib were not altered with lomustine, and galunisertib had a median half-life of ~8 hours. Median OS in months (95% credible interval [CrI]) for galunisertib + lomustine was 6.7 (range: 5.3-8.5), 8.0 (range: 5.7-11.7) for galunisertib alone, and 7.5 (range: 5.6-10.3) for placebo + lomustine. There was no difference in OS for patients treated with galunisertib + lomustine compared with placebo + lomustine [P (HR < 1) = 26%]. Median progression-free survival of ~2 months was observed in all 3 arms. Among 8 patients with IDH1 mutation, 7 patients were treated with galunisertib (monotherapy or with lomustine); OS ranged from 4 to 17 months. Patients treated with galunisertib alone had fewer drug-related grade 3/4 adverse events (n = 34) compared with lomustine-treated patients (10% vs 26%). Baseline PS, post discontinuation of bevacizumab, tumor size, and baseline levels of MDC/CCL22 were correlated with OS. CONCLUSIONS: Galunisertib + lomustine failed to demonstrate improved OS relative to placebo + lomustine. Efficacy outcomes were similar in all 3 arms. CLINICAL TRIAL REGISTRATION: NCT01582269, ClinicalTrials.gov. PMID- 26902852 TI - Heterotopic transplantation of a decellularized and recellularized whole porcine heart. AB - OBJECTIVES: One of the final treatments for end-stage heart failure is heart transplantation. However, a shortage of donor hearts has created a long waiting list and limited benefits. Our ultimate goal is to create a whole beating heart fabricated on an organ scaffold for human heart transplantation. Here, we successfully performed the first transplantation using a decellularized whole porcine heart with mesenchymal stem cells. METHODS: A porcine heart was harvested following cardiac arrest induced by a high-potassium solution and stored at -80 degrees C for 24 h. The porcine heart was completely decellularized with 1% sodium dodecyl sulphate and 1% Triton X-100 under the control of perfusion pressure (100 mmHg) and maintained at 37 degrees C. A decellularized whole-heart scaffold was sterilized with gamma irradiation. Cultured mesenchymal stem cells were collected and either infused into the ascending aorta or injected directly into the left ventricular wall. Finally, recellularized whole-heart scaffolds were transplanted into pigs under systemic anticoagulation treatment with heparin. Coronary artery angiography of the transplanted heart graft was performed. RESULTS: In our decellularization method, all cellular components were removed, preserving the heart extracellular matrix. Heterotopic transplantations were successfully performed using a decellularized heart and a recellularized heart. The scaffolds were well perfused, without bleeding from the surface or anastomosis site. Coronary angiography revealed a patent coronary artery in both scaffolds. The transplanted decellularized heart was harvested on Day 3. Haematoxylin and eosin staining showed thrombosis in the coronary arteries and migrated inflammatory cells. Haematoxylin and eosin staining of the transplanted recellularized heart showed similar findings, with the exception of injected mesenchymal stem cells. CONCLUSIONS: To the best of our knowledge, this is the first report of heterotopic transplantation of a decellularized whole porcine heart with mesenchymal stem cells. The scaffolds endured surgical procedures. We detected short-term coronary artery perfusion in the transplanted scaffolds by angiography. Future studies should analyse the histological features of transplanted decellularized scaffolds and optimize the system for recellularization to apply this unique technology clinically. PMID- 26902856 TI - Why We Need Nonpharmacologic Approaches to Manage Chronic Low Back Pain in Older Adults. PMID- 26902857 TI - Pressure dependence of electronic structure and superconductivity of the MnX (X = N, P, As, Sb). AB - A recently experimental discovered (Cheng et al., Phys. Rev. Lett. 114, 117001 (2015)) of superconductivity on the border of long-range magnetic order in the itinerant-electron helimagnet MnP via the application of high pressure makes MnP the first Mn-based superconductor. In this paper, we carry out first-principles calculations on MnX (X = N, P, As, Sb) and find superconducting critical temperature TC of MnP sharply increases near the critical pressure PC ~ 8 GPa, which is in good agreement with the experiments. Electron-phonon coupling constant lambda and electronic density of states at the Fermi level N (EF) are found to increase with pressure for MnP, which lead to the increase of TC of MnP. Moreover, we also find that the TC of MnAs and MnSb are higher than MnP, implying that the MnAs and MnSb may be the more potential Mn-based superconducting materials. PMID- 26902858 TI - Successful slush nitrogen vitrification of human ovarian tissue. AB - OBJECTIVE: To study whether slush nitrogen vitrification improves the preservation of human ovarian tissue. DESIGN: Control vs. treatment study. SETTING: University research laboratory. PATIENT(S): Ovarian biopsies collected from nine women (aged 14-35 years) during laparoscopic surgery for benign gynecologic conditions. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Ovarian cortical strips of 2 * 5 * 1 mm were vitrified with liquid or slush nitrogen. Fresh and vitrified cortical strips were analyzed for cryodamage and viability under light, confocal, and transmission electron microscopy. RESULT(S): Compared with liquid nitrogen, vitrification with slush nitrogen preserves [1] follicle quality (grade 1 follicles: fresh control, 50%; liquid nitrogen, 27%; slush nitrogen, 48%); [2] granulosa cell ultrastructure (intact cells: fresh control, 92%; liquid nitrogen, 45%; slush nitrogen, 73%), stromal cell ultrastructure (intact cells: fresh control, 59.8%; liquid nitrogen, 24%; slush nitrogen, 48.7%), and DNA integrity (TUNEL-positive cells: fresh control, 0.5%; liquid nitrogen, 2.3%; slush nitrogen, 0.4%); and [3] oocyte, granulosa, and stromal cell viability (oocyte: fresh control, 90%; liquid nitrogen, 63%; slush nitrogen, 87%; granulosa cells: fresh control, 93%; liquid nitrogen, 53%; slush nitrogen, 81%; stromal cells: fresh control, 63%; liquid nitrogen, 30%; slush nitrogen, 52%). CONCLUSION(S): The histology, ultrastructure, and viability of follicles and stromal cells are better preserved after vitrification with slush nitrogen compared with liquid nitrogen. PMID- 26902855 TI - Therapeutic efficacy of apelin on transplanted mesenchymal stem cells in hindlimb ischemic mice via regulation of autophagy. AB - Mesenchymal stem cells (MSCs)-based therapy provides a promising avenue for the management of peripheral arterial disease (PAD). However, engrafted MSCs are subjected to acute cell death in the ischemic microenvironment. Apelin has been shown to protect bone marrow MSCs against apoptosis although the mechanism of action remains elusive. Here we demonstrated that apelin promoted functional survival of AD-MSCs in ischemic hindlimbs and provoked a synergetic effect with AD-MSCs to restore hindlimb blood perfusion and limb functions. Further in vitro studies revealed that a biphasic response in autophagy was induced by apelin in AD-MSCs during hypoxia and hypoxia/reoxygenation (H/R) stages to exert cytoprotective effects against H/R injury. Mechanistically, apelin increased the viability of AD-MSCs via promoting protective autophagy during hypoxia, which was accompanied with activation of AMPK and inhibition of mammalian target of rapamycin (mTOR). To the contrary, apelin suppressed autophagic cell death during reoxygenation, which was accompanied with activation of Akt and inhibition of Beclin1. Our findings indicated that apelin facilitated AD-MSCs-based therapy in PAD, possibly through promoting survival of AD-MSCs by way of autophagy regulation. Our data support the promises of apelin as a novel strategy to improve MSC-based therapy for PAD, possibly through autophagy modulation in MSCs. PMID- 26902859 TI - Validation of a next-generation sequencing-based protocol for 24-chromosome aneuploidy screening of blastocysts. AB - OBJECTIVE: To validate a 24-chromosome aneuploidy preimplantation genetic screening protocol based on multiple annealing and looping-based amplification cycle (MALBAC) and next-generation sequencing (NGS). DESIGN: Single-nucleotide polymorphism (SNP) array and MALBAC-NGS analysis. SETTING: University-affiliated in vitro fertilization (IVF) center. PATIENT(S): Fifteen women from whom 30 blastocysts were obtained for genotyping. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Chromosomal status comparison of results of array comparative genomic hybridization (aCGH), SNP array, and MALBAC-NGS for 24-chromosome aneuploidy screening. RESULT(S): Trophectoderm biopsy samples from blastocysts were first analyzed using array comparative genomic hybridization (aCGH); the embryos with detected with chromosomal abnormalities were rebiopsied, and dissociated into two portions, and subjected to SNP array and MALBAC-NGS for 24 chromosome aneuploidy screening. All 30 samples were successfully genotyped by array CGH, SNP array, and MALBAC-NGS. All blastocysts were correctly identified as aneuploid, and there was a 100% concordance in terms of diagnosis provided between the three methods. In the 720 detected chromosomes, the concordance rate between MALBAC-NGS and array CGH was 99.31% (715 of 720), and the concordance rate between MALBAC-NGS and SNP array was 99.58% (717 of 720). When compared with aCGH, MALBAC-NGS specificity for aneuploidy call was 99.85% (674 of 675; 95% CI, 99.17-99.97) with a sensitivity of 91.11% (41 of 45; 95% CI, 79.27-96.49). When compared with SNP array, MALBAC-NGS specificity for aneuploidy call was 99.85% (676 of 677; 95% CI, 99.17-99.97) with a sensitivity of 95.35% (41 of 43; 95% CI, 85.54-98.72). CONCLUSION(S): MALBAC-NGS provides concordant chromosomal results when compared with aCGH and SNP array in blastocysts with chromosomal abnormalities. PMID- 26902860 TI - Evidence-based approach to unexplained infertility: a systematic review. AB - OBJECTIVE: To summarize the available evidence for the efficacy of various treatments for unexplained infertility. DESIGN: Systematic review. SETTING: Not applicable. PATIENT(S): Patients aged 18-40 years with unexplained infertility. INTERVENTION(S): Clomiphene citrate, letrozole, timed intercourse, IUI, gonadotropins, IVF, and IVF-intracytoplasmic sperm injection. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate, ongoing pregnancy rate, and live birth rate. RESULT(S): Thirteen studies with a total of 3,081 patients were identified by systematic search and met inclusion criteria. The available literature demonstrates that expectant management may be comparable to treatment with clomiphene and timed intercourse or IUI. Clomiphene may be more effective than letrozole, and treatment with gonadotropins seems more effective, albeit with significantly higher risk of multiple gestations than either oral agent. On the basis of current data, IVF, with or without intracytoplasmic sperm injection, is no more effective than gonadotropins with IUI for unexplained infertility. CONCLUSION(S): Adequately powered, randomized controlled trials that compare all of the available treatments for unexplained infertility are needed. Until such data are available, clinicians should individualize the management of unexplained infertility with appropriate counseling regarding the empiric nature of current treatment options including IVF. PMID- 26902862 TI - Development of molecular markers, based on chloroplast and ribosomal DNA regions, to discriminate three popular medicinal plant species, Cynanchum wilfordii, Cynanchum auriculatum, and Polygonum multiflorum. AB - Identification of plant species is important for standardizing herbal medicine. Cynanchum wilfordii (Baekshuoh in Korean) and Polygonum multiflorum (Hashuoh in Korean) are important oriental medicinal herbs in Korea, Japan, and China. Cynanchum auriculatum is a faster growing and more productive plant than C. wilfordii; and, it is not recognized as a medicinal plant in the Korean Pharmacopoeia. C. wilfordii, P. multiflorum, and C. auriculatum are often misidentified in the Korean herbal medicine marketplace due to their morphological similarities and similar names. In this study, we investigated molecular authentication of these three medicinal plants using DNA sequences in the TrnL-F chloroplast intergenic region. Specific species identification was achieved by detecting allelic variations of single nucleotide polymorphisms (SNPs) using amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and high resolution melting curve analysis. Our results demonstrate that the intraspecific genetic distance between C. wilfordii and C. auriculatum is relatively low. We also developed a quantitative PCR assay using species specific TrnL-F primers, which allowed us to estimate the ratio of C. wilfordii and C. auriculatum using varying ratios of mixed genomic DNA template from the two species. Additionally, to identify species in hybrid plants produced by cross fertilization, we analyzed nuclear ribosomal DNA internal transcribed spacer regions in C. wilfordii and C. auriculatum by ARMS-PCR. Our results indicate that SNP-based molecular markers, usable to barcode tools could provide efficient and rapid authentication of these closely related medicinal plant species, and will be useful for preventing the distribution of products contaminated with adulterants. PMID- 26902863 TI - Activation of sputter-processed indium-gallium-zinc oxide films by simultaneous ultraviolet and thermal treatments. AB - Indium-gallium-zinc oxide (IGZO) films, deposited by sputtering at room temperature, still require activation to achieve satisfactory semiconductor characteristics. Thermal treatment is typically carried out at temperatures above 300 degrees C. Here, we propose activating sputter- processed IGZO films using simultaneous ultraviolet and thermal (SUT) treatments to decrease the required temperature and enhance their electrical characteristics and stability. SUT treatment effectively decreased the amount of carbon residues and the number of defect sites related to oxygen vacancies and increased the number of metal oxide (M-O) bonds through the decomposition-rearrangement of M-O bonds and oxygen radicals. Activation of IGZO TFTs using the SUT treatment reduced the processing temperature to 150 degrees C and improved various electrical performance metrics including mobility, on-off ratio, and threshold voltage shift (positive bias stress for 10,000 s) from 3.23 to 15.81 cm(2)/Vs, 3.96 * 10(7) to 1.03 * 10(8), and 11.2 to 7.2 V, respectively. PMID- 26902864 TI - Acute Calcific Bursitis After Ultrasound-Guided Percutaneous Barbotage of Rotator Cuff Calcific Tendinopathy: A Case Report. AB - Ultrasound-guided percutaneous barbotage is an effective treatment for rotator cuff calcific tendinopathy, providing rapid and substantial pain relief. We present the case of a 49-year-old woman with aggravated pain early after ultrasound-guided barbotage of a large calcific deposit in the supraspinatus tendon. Subsequent examination revealed a thick calcification spreading along the subacromial-subdeltoid bursa space, suggesting acute calcific bursitis complicated by barbotage. Additional barbotage alleviated her pain completely. Therefore, a high index of suspicion for acute calcific bursitis is required in patients with unresolved or aggravated pain after barbotage. Repeated barbotage could be effective for this condition. PMID- 26902861 TI - SMAD7, an antagonist of TGF-beta signaling, is a candidate of prenatal skeletal muscle development and weaning weight in pigs. AB - SMAD7 promotes and enhances skeletal muscle differentiation by inhibiting transforming growth factor beta (TGF-beta)/activin signaling and bone morphogenetic protein (BMP) pathways. However, its function, the mechanism regulating its translation, and its association with production meat traits remain unclear in pigs. In this study, we explored SMAD7 gene spatio-temporal and tissue distribution, conducted a single nucleotide polymorphism association analysis, and examined regulation of its expression during skeletal muscle development. We found that SMAD7 was positively related to TGF-beta pathway genes and mainly expressed in prenatal developing muscle, and dual luciferase and western blot assays demonstrated that SMAD7 expression was regulated by miRNA-21 at the protein level via inhibition of mRNA translation. Finally, the association analysis showed that a single nucleotide mutation (Exon 4_28816;C/A) was significantly associated with the weaning weight of piglets among Yorkshire pigs. These data indicate that SMAD7 plays a potentially important role in mammalian prenatal skeletal muscle development and is a candidate gene for promoting greater weaning weight in pig breeding. PMID- 26902865 TI - A Case Series: The Identification of Buried Bumper Syndrome With Abdominal Computed Tomography Scan in Two Severely Brain Injured Rehabilitation Patients. AB - Buried bumper syndrome is a potentially dangerous complication related to percutaneous endoscopic gastrostomy tube placement. Early diagnosis of this condition is important to avoid further complications related to subcutaneous or intraperitoneal administration of tube feedings. However, diagnosis in persons with altered mental status due to brain injury is challenging because of the patient's lack of ability to communicate and report symptoms. We present 2 case studies that demonstrate both the importance of early diagnosis and management and the lack of adequate sensitivity of a Gastrografin-aided kidney, ureter, and bladder (KUB) study. PMID- 26902867 TI - Genetically modified mosquitos may be used in fight against Zika. PMID- 26902866 TI - Who May Benefit From Armeo Power Treatment? A Neurophysiological Approach to Predict Neurorehabilitation Outcomes. AB - BACKGROUND: The Armeo Power, a rehabilitation exoskeleton that allows early treatment of motor disabilities, provides intelligent arm support in a large 3 dimensional work space, thus enabling patients to perform intensive, repetitive, and goal-oriented exercises. This device could efficiently induce new connections and facilitate plasticity phenomena potentiation. Knowledge of the potential brain plasticity reservoir after brain damage constitutes a prerequisite for an optimal rehabilitation strategy. OBJECTIVE: To identify potential neurophysiologic markers predicting the responsiveness of stroke patients to upper limb robotic treatment. DESIGN: Prospective cohort study. SETTING: Behavioral and Robotic Neurorehabilitation Laboratory of IRCCS Centro Neurolesi Bonino-Pulejo, Messina, Italy. PATIENTS: We enrolled 35 patients who had sustained a first-ever ischemic supratentorial stroke at least 2 months before enrollment and had unilateral hemiplegia. METHODS: All patients underwent 40 Armeo Power training sessions that lasted 1 hour each (ie, 5 times a week for 8 weeks). MAIN OUTCOME MEASUREMENTS: We assessed the spasticity and motor function of the upper limb by means of the Modified Ashworth scale and Fugl-Meyer assessment, respectively. Moreover, we evaluated the cortical excitability and plasticity potential of the bilateral primary motor areas in response to the repetitive paired associative stimulation paradigm using transcranial magnetic stimulation and Armeo Power kinematic parameters. RESULTS: The patients who showed significant repetitive paired associative stimulation aftereffects at baseline exhibited an evident increase of cortical plasticity in the affected hemisphere (motor evoked potential amplitude increase, P = .03), a decrease of interhemispheric inhibition (affected hemisphere cortical silent period duration decrease, P = .01; unaffected hemisphere cortical silent period duration increase, P = .004; repetitive paired associative stimulation aftereffect increase, P = .008). Such findings were paralleled by clinical improvements (Fugl Meyer, P = .04) and Armeo Power kinematic improvements (elbow flexion/extension, P = .02; shoulder range of movement, P = .002). CONCLUSIONS: Our data suggest that use of Armeo Power may improve upper limb motor function recovery as predicted by reshaping of cortical and transcallosal plasticity, according to the baseline cortical excitability. LEVEL OF EVIDENCE: IV. PMID- 26902868 TI - [Interventional therapy of aortic valve stenosis in Germany]. AB - BACKGROUND: Transcatheter aortic valve implantation (TAVI) has gained importance in recent years for the treatment of symptomatic aortic stenosis in Germany. OBJECTIVE: This article discusses the indications, the procedure itself and safety issues in TAVI. MATERIAL AND METHODS: Randomized controlled trials, registry studies, guidelines and expert recommendations are discussed. RESULTS: Inoperable patients as well as patients >= 75 years with a high perioperative risk and patients >= 85 years should primarily be treated by TAVI. The decision must be made following discussions in a heart team. If no contraindications are detected the TAVI procedure should be performed via the transfemoral approach with the patient under conscious sedation. In recent years there has been a significant reduction in complication rates. CONCLUSION: In Germany TAVI is the standard of care for surgical high-risk and inoperable patients with aortic valve stenosis. PMID- 26902869 TI - Team-Based Development of Medical Devices: An Engineering-Business Collaborative. AB - There is a global shift in the teaching methodology of science and engineering toward multidisciplinary, team-based processes. To meet the demands of an evolving technical industry and lead the way in engineering education, innovative curricula are essential. This paper describes the development of multidisciplinary, team-based learning environments in undergraduate and graduate engineering curricula focused on medical device design. In these programs, students actively collaborate with clinicians, professional engineers, business professionals, and their peers to develop innovative solutions to real-world problems. In the undergraduate senior capstone courses, teams of biomedical engineering (BME) and business students have produced and delivered numerous functional prototypes to satisfied clients. Pursuit of commercialization of devices has led to intellectual property (IP) disclosures and patents. Assessments have indicated high levels of success in attainment of student learning outcomes and student satisfaction with their undergraduate design experience. To advance these projects toward commercialization and further promote innovative team-based learning, a Master of Engineering (MEng) in Design and Commercialization was recently launched. The MEng facilitates teams of graduate students in engineering, life sciences, and business who engage in innovation-commercialization (IC) projects and coursework that take innovative ideas through research and development (R&D) to create marketable devices. The activities are structured with students working together as a "virtual company," with targeted outcomes of commercialization (license agreements and new start ups), competitive job placement, and/or career advancement. PMID- 26902870 TI - Thyroid hormone levels in the cerebrospinal fluid correlate with disease severity in euthyroid patients with Alzheimer's disease. PMID- 26902872 TI - Screening of Riboflavin-Producing Lactobacilli by a Polymerase-Chain-Reaction Based Approach and Microbiological Assay. AB - Riboflavin has an important role in various cellular metabolic activities through its participation in oxidation-reduction reactions. In this study, as many as 60 lactobacilli were screened for the presence or absence of riboflavin biosynthesis genes and riboflavin production. Of these, only 14 strains were able to grow in a commercial riboflavin-free medium. We observed that the presence of riboflavin biosynthesis genes is strain-specific across different species of lactobacilli. The microbiological assay was found to be appreciably reproducible, sensitive, rapid, and inexpensive and, hence, can be employed for screening the riboflavin producing strains. The study thus represents a convenient and efficient method for selection of novel riboflavin producers. These riboflavin(+) strains thus identified and characterized could be explored as potent candidates for the development of a wide range of dairy- and cereal-based foods for the delivery of in situ riboflavin to consumers. PMID- 26902871 TI - Sexual function and depressive symptoms in young women with elevated macroprolactin content: a pilot study. AB - Elevated prolactin levels seem to be associated with impaired sexuality. The clinical significance of macroprolactinemia, associated with the predominance of high molecular mass circulating forms of prolactin, is still poorly understood. This study was aimed at investigating sexual function in young women with macroprolactinemia. The study enrolled 14 young women with macroprolactinemia, 14 with increased monomeric prolactin levels, as well as 14 age- and weight-matched healthy women. All patients completed a questionnaire evaluating female sexual function (Female Sexual Function Index-FSFI), as well as a questionnaire assessing the presence and severity of depressive symptoms (Beck Depression Inventory Second Edition-BDI-II). Apart from total prolactin levels and macroprolactin content, circulating levels of thyrotropin, total testosterone, and 17-beta estradiol were also measured. Patients with elevated monomeric prolactin levels had a lower total FSFI score, as well as lower scores for all domains: sexual desire, sexual arousal, lubrication, orgasm, sexual satisfaction, and dyspareunia. These scores correlated with total and monomeric prolactin levels. In turn, women with macroprolactinemia were characterized by a lower score for sexual desire, and only this score correlated with total prolactin levels and macroprolactin content. The total score in the BDI-II questionnaire was higher in patients with hyper- and macroprolactinemia than in the control subjects. Contrary to multidimensional impairment of sexual function in women with elevated monomeric prolactin, macroprolactinemia only seems to disturb sexual desire. PMID- 26902873 TI - Localized soft elasticity in liquid crystal elastomers. AB - Synthetic approaches to prepare designer materials that localize deformation, by combining rigidity and compliance in a single material, have been widely sought. Bottom-up approaches, such as the self-organization of liquid crystals, offer potential advantages over top-down patterning methods such as photolithographic control of crosslink density, relating to the ease of preparation and fidelity of resolution. Here, we report on the directed self-assembly of materials with spatial and hierarchical variation in mechanical anisotropy. The highly nonlinear mechanical properties of the liquid crystalline elastomers examined here enables strain to be locally reduced >15-fold without introducing compositional variation or other heterogeneities. Each domain (?0.01 mm(2)) exhibits anisotropic nonlinear response to load based on the alignment of the molecular orientation with the loading axis. Accordingly, we design monoliths that localize deformation in uniaxial and biaxial tension, shear, bending and crack propagation, and subsequently demonstrate substrates for globally deformable yet locally stiff electronics. PMID- 26902874 TI - 2016 ACC Lifelong Learning Competencies for General Cardiologists: A Report of the ACC Competency Management Committee. PMID- 26902875 TI - Co-occurring risk factors for current cigarette smoking in a U.S. nationally representative sample. AB - INTRODUCTION: Relatively little has been reported characterizing cumulative risk associated with co-occurring risk factors for cigarette smoking. The purpose of the present study was to address that knowledge gap in a U.S. nationally representative sample. METHODS: Data were obtained from 114,426 adults (>=18years) in the U.S. National Survey on Drug Use and Health (years 2011-13). Multiple logistic regression and classification and regression tree (CART) modeling were used to examine risk of current smoking associated with eight co occurring risk factors (age, gender, race/ethnicity, educational attainment, poverty, drug abuse/dependence, alcohol abuse/dependence, mental illness). RESULTS: Each of these eight risk factors was independently associated with significant increases in the odds of smoking when concurrently present in a multiple logistic regression model. Effects of risk-factor combinations were typically summative. Exceptions to that pattern were in the direction of less than-summative effects when one of the combined risk factors was associated with generally high or low rates of smoking (e.g., drug abuse/dependence, age >=65). CART modeling identified subpopulation risk profiles wherein smoking prevalence varied from a low of 11% to a high of 74% depending on particular risk factor combinations. Being a college graduate was the strongest independent predictor of smoking status, classifying 30% of the adult population. CONCLUSIONS: These results offer strong evidence that the effects associated with common risk factors for cigarette smoking are independent, cumulative, and generally summative. The results also offer potentially useful insights into national population risk profiles around which U.S. tobacco policies can be developed or refined. PMID- 26902876 TI - Some context for understanding the place of the general educational development degree in the relationship between educational attainment and smoking prevalence. AB - INTRODUCTION: Individuals with a General Educational Development (GED) degree have the highest smoking prevalence of any education level, including high school dropouts without a GED. Yet little research has been reported providing a context for understanding the exception that the GED represents in the otherwise graded inverse relationship between educational attainment and smoking prevalence. We investigated whether the GED may be associated with a general riskier profile that includes but is not limited to increased smoking prevalence. METHOD: Data were obtained from three years (2011-2013) of the National Survey on Drug Use and Health ([NSDUH], N=55,940]). Prevalence of risky repertoire indicators (e.g., ever arrested, seldom/never wears a seatbelt), indicators of social instability (e.g., frequent relocations), and risky demographic characteristics (e.g., male gender) were compared among high school dropouts, GED holders, and high school graduates using Rao-Scott chi square goodness-of-fit tests and multiple logistic regression. RESULTS: Those with GEDs differed significantly between both high school dropouts and high school graduates across 19 of 27 (70.4%) risk indicators. Controlling for risky profile characteristics accounted for a significant but limited (25-30%) proportion of the variance in smoking prevalence across these three education levels. CONCLUSION: GED holders exhibit a broad high risk profile of which smoking is just one component. Future research evaluating additional risk indicators and mechanisms that may underpin this generalized risky repertoire are likely needed for a more complete understanding of GED's place in the important relationship between educational attainment and smoking prevalence. PMID- 26902877 TI - Comparison of oncologic outcomes between sarcomatoid and clear cell renal cell carcinoma. AB - BACKGROUND: Sarcomatoid renal cell carcinoma (sRCC) is a rare histological subtype that is associated with unfavorable prognosis. We sought to examine the effect of sRCC on cancer-specific mortality (CSM) relative to clear cell renal cell carcinoma (ccRCC), after adjusting for other variables, as well as other cause mortality (OCM). METHODS: We relied on the Surveillance, Epidemiology, and End Results-Medicare database from 2000 to 2009 to identify a cohort of 7916 patients with either sRCC (n = 234) or ccRCC (n = 7682) who received surgery as primary treatment. Patient, tumor, and treatment characteristics were evaluated. Then, 5-year smoothed Poisson regression CSM and OCM estimates were generated for stage-by-stage comparisons between sRCC and ccRCC. A multivariable competing risks regression model predicting CSM and adjusting for several patient and tumor characteristics, as well as OCM, was finally fitted. RESULTS: Compared to ccRCC patients, sRCC patients had more advanced and more aggressive disease at diagnosis. Specifically, 48 and 7 % of sRCC and ccRCC patients presented with stage IV disease, respectively (p < 0.001). Overall, 5-year CSM and OCM estimates were 67 and 17 % for sRCC patients and 14 and 19 % for ccRCC patients. In stage by-stage analyses, sRCC was invariably associated with worse CSM. After adjusting for several characteristics as well as OCM, sRCC was associated with a 3.2 higher risk of CSM compared with ccRCC. CONCLUSIONS: Patients with sRCC are present with more advanced disease. Moreover, sRCC is associated with a higher rate of CSM, even after adjusting for several characteristics and OCM. PMID- 26902878 TI - Apparent diffusion coefficient value is a strong predictor of unsuspected aggressiveness of prostate cancer before radical prostatectomy. AB - PURPOSE: To evaluate the use of multiparametric MRI (mp MRI) parameters in order to predict prostate cancer aggressiveness as defined by pathological Gleason score or molecular markers in a cohort of patients defined with a Gleason score of 6 at biopsy. METHODS: Sixty-seven men treated by radical prostatectomy (RP) for a low grade (Gleason 6) on biopsy and mp MRI before biopsy were selected. The cycle cell proliferation (CCP) score assessed by the Prolaris test and Ki-67/PTEN expression assessed by immunohistochemistry were quantified on the RP specimens. RESULTS: 49.25 % of the cancers were undergraded on biopsy compared to the RP specimens. Apparent diffusion coefficient (ADC) < 0.80 * 10(-3) mm(2)/s (P value 0.003), Likert score >4 (P value 0.003) and PSA density >0.15 ng/ml/cc (P value 0.035) were significantly associated with a higher RP Gleason score. Regarding molecular markers of aggressiveness, ADC < 0.80 * 10(-3) mm(2)/s and Likert score >4 were also significantly associated with a positive staining for Ki-67 (P value 0.039 and 0.01, respectively). No association was found between any analyzed MRI or clinical parameter and the CCP score. CONCLUSION: Decreasing ADC value is a stronger indicator of aggressive prostate cancer as defined by molecular markers or postsurgical histology than biopsy characteristics. PMID- 26902879 TI - Dysprosium(III) complexes with a square-antiprism configuration featuring mononuclear single-molecule magnetic behaviours based on different beta diketonate ligands and auxiliary ligands. AB - Three mononuclear dysprosium(III) complexes derived from three beta-diketonate ligands, 4,4,4-trifluoro-1-(4-methylphenyl)-1,3-butanedione (tfmb), 4,4,4 trifluoro-1-(4-fluorophenyl)-1,3-butanedione (tffb) and 4,4,4-trifluoro-1-(2 naphthyl)-1,3-butanedione (tfnb) as well as auxiliary ligands, 5-nitro-1,10 phenanthroline (5-NO2-Phen), DMF and 2,2'-bipyridine (bpy) have been synthesized and structurally characterized, namely [Dy(5-NO2-Phen)(tfmb)3] (1), [Dy(DMF)2(tffb)3] (2) and [Dy(bpy)2(tfnb)3].0.5(1,4-dioxane) (3). The metal ions in 1-3 adopt an approximately square-antiprismatic (SAP) coordination environment with D4d axial symmetry. The magnetic properties of 1-3 have been investigated, displaying weak out-of-phase AC signals under a zero-DC field. With an applied DC field of 1200 Oe, the quantum tunnelling of the magnetization was suppressed in 1 3 with the pre-exponential factor tau0 = 5.3 * 10(-7) s and the effective barrier DeltaE/kB = 83 K for 1 as well as the pre-exponential factor tau0 = 3.09 * 10(-7) s and the effective barrier DeltaE/kB = 39 K for 3. Interestingly, for the frequency dependence of the out-of-phase (chi'') of the AC susceptibility of 2, two slow relaxation of the magnetization processes occurred under the applied magnetic field of 1200 Oe, corresponding to the fast relaxation (FR) phase and slow relaxation (SR) phase, respectively. Arrhenius analysis gave the effective energy barrier (DeltaE/kB) of 55 K and the pre-exponential factor (tau0) of 8.23 * 10(-12) for the SR. It is thus very likely that the FR process in complex 2 results from QTM enhanced by dipolar interactions between the Dy ions or the presence of the applied field. The structure-property relationship of some Dy(III) based mononuclear SMMs with the SAP configuration was further discussed. PMID- 26902881 TI - Comparison of Molecular Species Distribution of DHA-Containing Triacylglycerols in Milk and Different Infant Formulas by Liquid Chromatography-Mass Spectrometry. AB - Long-chain polyunsaturated fatty acids (LC-PUFA) are an important nutritional lipid and have potential in being able to promote human health. Docosahexaenoic acid (DHA, C22:6omega3) is often added in infant formulas to meet the nutritional requirement of formula-fed infants. A comprehensive survey on DHA-containing triacylglycerol (DHA-TAG) molecular species has been conducted for seven infant formulas (IFs) sourced from Australia, Europe, and the USA as well as bovine milk and human milk. Using LC-triple quadrupole MS and LC-LTQ-orbitrap MS we were able to identify and quantify 56 DHA-TAG species in these samples; the fatty acid structure of these species was assigned using their MS(2) spectra. The species composition of DHA-TAG was found to be different between bovine milk, human milk, and IFs and also between different brands of IFs. Bovine milk and human milk contain DHA-TAG of smaller molecular size (728-952 Da), whereas five out of the seven IF samples contain species of broader mass range (from 728 to 1035 Da). Our study indicates that two types of DHA were used in the seven IF products surveyed and that there is very large difference in molecular species distribution in different IF products that may influence the fine nutritional profile and biological functions of IF products. PMID- 26902882 TI - Abstracts from the 2016 American College of Medical Toxicology (ACMT) Annual Scientific Meeting. PMID- 26902880 TI - Repositioning tolcapone as a potent inhibitor of transthyretin amyloidogenesis and associated cellular toxicity. AB - Transthyretin (TTR) is a plasma homotetrameric protein implicated in fatal systemic amyloidoses. TTR tetramer dissociation precedes pathological TTR aggregation. Native state stabilizers are promising drugs to treat TTR amyloidoses. Here we repurpose tolcapone, an FDA-approved molecule for Parkinson's disease, as a potent TTR aggregation inhibitor. Tolcapone binds specifically to TTR in human plasma, stabilizes the native tetramer in vivo in mice and humans and inhibits TTR cytotoxicity. Crystal structures of tolcapone bound to wild-type TTR and to the V122I cardiomyopathy-associated variant show that it docks better into the TTR T4 pocket than tafamidis, so far the only drug on the market to treat TTR amyloidoses. These data indicate that tolcapone, already in clinical trials for familial amyloid polyneuropathy, is a strong candidate for therapeutic intervention in these diseases, including those affecting the central nervous system, for which no small-molecule therapy exists. PMID- 26902883 TI - Integrin "endoadhesome" signaling suppresses anoikis. PMID- 26902884 TI - Isolation and characterization of a novel type of rotavirus species A in sugar gliders (Petaurus breviceps). AB - To estimate the risk of interspecies transmission of rotavirus species A (RVA) from exotic pets to other mammalian species, the prevalence of RVA in sugar gliders (Petaurus breviceps) was investigated. RVAs were detected in 10 of 44 sugar gliders by reverse transcription (RT)-semi-nested PCR. These viruses were classified as G27P[3] and G27P[36] genotypes, with G27 and P[36] being new genotypes as assigned by the Rotavirus Classification Working Group. To characterize sugar glider RVA in detail, one strain, RVA/SugarGlider tc/JPN/SG385/2012/G27P[36] (SG385-tc), was isolated. All of the genes of the strain were classified as new genotypes (G27-P[36]-I19-R10-C10-M9-A20-N11-T13-E17 H12). The enterotoxin domain in NSP4, which is important for the induction of diarrhoea, was conserved between SG385-tc and previously reported mammalian strains, suggesting the potential of sugar glider RVA to cause diarrhoea in mammalian species. In fact, seven out of nine suckling mice inoculated orally with 3.9 * 104 f.f.u. of strain SG385-tc had diarrhoea and the 50 % diarrhoea inducing dose (DD50) of strain SG385-tc in suckling mice was 1.2 * 104 f.f.u. Our findings suggest that sugar glider RVA is infective to and possibly pathogenic in other mammalian species. PMID- 26902885 TI - Electrical characterization of benzenedithiolate molecular electronic devices with graphene electrodes on rigid and flexible substrates. AB - We investigated the electrical characteristics of molecular electronic devices consisting of benzenedithiolate self-assembled monolayers and a graphene electrode. We used the multilayer graphene electrode as a protective interlayer to prevent filamentary path formation during the evaporation of the top electrode in the vertical metal-molecule-metal junction structure. The devices were fabricated both on a rigid SiO2/Si substrate and on a flexible poly(ethylene terephthalate) substrate. Using these devices, we investigated the basic charge transport characteristics of benzenedithiolate molecular junctions in length- and temperature-dependent analyses. Additionally, the reliability of the electrical characteristics of the flexible benzenedithiolate molecular devices was investigated under various mechanical bending conditions, such as different bending radii, repeated bending cycles, and a retention test under bending. We also observed the inelastic electron tunneling spectra of our fabricated graphene electrode molecular devices. Based on the results, we verified that benzenedithiolate molecules participate in charge transport, serving as an active tunneling barrier in solid-state graphene-electrode molecular junctions. PMID- 26902886 TI - Isolation of a recombinant antibody specific for a surface marker of the corneal endothelium by phage display. AB - Cell surface antigens are important targets for monoclonal antibodies, but they are often difficult to work with due to their association with the cell membrane. Phage display is a versatile technique that can be applied to generate binders against difficult targets. Here we used antibody phage display to isolate a binder for a rare and specialized cell, the human corneal endothelial cell. The human corneal endothelium is a medically important cell layer; defects in this layer account for about half of all corneal transplants. Despite its importance, no specific antigens have been found to mark this cell type. By panning a phage library directly on human corneal endothelial cells, we isolated an antibody that bound to these cells and not the other types of corneal cells. Subsequently, we identified the antibody's putative target to be CD166 by immunoprecipitation and mass spectrometry. This approach can be used to isolate antibodies against other poorly-characterized cell types, such as stem cells or cancer cells, without any prior knowledge of their discriminating markers. PMID- 26902887 TI - DNA methylation profiles in African American prostate cancer patients in relation to disease progression. AB - This study examined whether differential DNA methylation is associated with clinical features of more aggressive disease at diagnosis and prostate cancer recurrence in African American men, who are more likely to die from prostate cancer than other populations. Tumor tissues from 76 African Americans diagnosed with prostate cancer who had radical prostatectomy as their primary treatment were profiled for epigenome-wide DNA methylation levels. Long-term follow-up identified 19 patients with prostate cancer recurrence. Twenty-three CpGs were differentially methylated (FDR q<=0.25, mean methylation difference>=0.10) in patients with vs. without recurrence, including CpGs in GCK, CDKL2, PRDM13, and ZFR2. Methylation differences were also observed between men with metastatic lethal prostate cancer vs. no recurrence (five CpGs), regional vs. local pathological stage (two CpGs), and higher vs. lower tumor aggressiveness (one CpG). These results indicate that differentially methylated CpG sites identified in tumor tissues of African American men may contribute to prostate cancer aggressiveness. PMID- 26902889 TI - Bayesian demography 250 years after Bayes. AB - Bayesian statistics offers an alternative to classical (frequentist) statistics. It is distinguished by its use of probability distributions to describe uncertain quantities, which leads to elegant solutions to many difficult statistical problems. Although Bayesian demography, like Bayesian statistics more generally, is around 250 years old, only recently has it begun to flourish. The aim of this paper is to review the achievements of Bayesian demography, address some misconceptions, and make the case for wider use of Bayesian methods in population studies. We focus on three applications: demographic forecasts, limited data, and highly structured or complex models. The key advantages of Bayesian methods are the ability to integrate information from multiple sources and to describe uncertainty coherently. Bayesian methods also allow for including additional (prior) information next to the data sample. As such, Bayesian approaches are complementary to many traditional methods, which can be productively re-expressed in Bayesian terms. PMID- 26902891 TI - Bacillus circulans exopolysaccharide: Production, characterization and bioactivities. AB - A bacterium with the ability to produce appreciable amount of exopolysaccharide was isolated from slimy layer of coconut. 16S rDNA analysis identified the organism as Bacillus circulans. EPS production was observed at all stages of culture growth and reached maximum of 0.065mg/ml by 96h, which on further incubation started to decrease. Response Surface Methodology using Box Behnken design has shown the influence of sucrose which was found to be directly proportional to exopolysaccharide production with production reaching 1.09mg/ml. HPLC analysis identified the presence of glucose, mannose, fructose and verbascose and NMR analysis confirmed the presence of glucose, mannose and galactose. Even though the extracted B. circulans EPS did not show appreciable anti-bacterial or anti-fungal activity, it exhibited appreciable antioxidant, anti-inflammatory and anti-tumor activity. PMID- 26902890 TI - Dilute solution properties of canary seed (Phalaris canariensis) starch in comparison to wheat starch. AB - Dilute solution properties of an unknown starch are important to understand its performance and applications in food and non-food industries. In this paper, rheological and molecular properties (intrinsic viscosity, molecular weight, shape factor, voluminosity, conformation and coil overlap parameters) of the starches from two hairless canary seed varieties (CO5041 & CDC Maria) developed for food use were evaluated in the dilute regime (Starch dispersions in DMSO (0.5g/dl)) and compared with wheat starch (WS). The results showed that Higiro model is the best among five applied models for intrinsic viscosity determination of canary seed starch (CSS) and WS on the basis of coefficient of determination (R(2)) and root mean square error (RMSE). WS sample showed higher intrinsic viscosity value (1.670dl/g) in comparison to CSS samples (1.325-1.397dl/g). Berry number and the slope of master curve demonstrated that CSS and WS samples were in dilute domain without entanglement occurrence. The shape factor suggested spherical and ellipsoidal structure for CO5041 starch and ellipsoidal for CDC Maria starch and WS. The molecular weight, coil radius and coil volume of CSSs were smaller than WS. The behavior and molecular characterization of canary seed starch showed its unique properties compared with wheat starch. PMID- 26902888 TI - Resveratrol induces autophagy by directly inhibiting mTOR through ATP competition. AB - Resveratrol (RSV) is a natural polyphenol that has a beneficial effect on health, and resveratrol-induced autophagy has been suggested to be a key process in mediating many beneficial effects of resveratrol, such as reduction of inflammation and induction of cancer cell death. Although various resveratrol targets have been suggested, the molecule that mediates resveratrol-induced autophagy remains unknown. Here, we demonstrate that resveratrol induces autophagy by directly inhibiting the mTOR-ULK1 pathway. We found that inhibition of mTOR activity and presence of ULK1 are required for autophagy induction by resveratrol. In line with this mTOR dependency, we found that resveratrol suppresses the viability of MCF7 cells but not of SW620 cells, which are mTOR inhibitor sensitive and insensitive cancer cells, respectively. We also found that resveratrol-induced cancer cell suppression occurred ULK1 dependently. For the mechanism of action of resveratrol on mTOR inhibition, we demonstrate that resveratrol directly inhibits mTOR. We found that resveratrol inhibits mTOR by docking onto the ATP-binding pocket of mTOR (i.e., it competes with ATP). We propose mTOR as a novel direct target of resveratrol, and inhibition of mTOR is necessary for autophagy induction. PMID- 26902892 TI - Preparation of a novel chitosan-microcapsules/starch blend film and the study of its drug-release mechanism. AB - A novel drug delivery system, chitosan-microcapsules/starch blend film for antofloxacin controlled release, was prepared, and characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (X-RD), thermogravimetry and derivative thermogravimetry (TG/DTG), and scanning electron microscopy (SEM). Following incorporation of the chitosan-microcapsules in the film matrix, the synergistic interactions between these drug-carriers were significant. The thermostability and mechanical properties of the blend film were greatly improved by the incorporation of the microcapsules. The water resistance of the blend film was enhanced by increasing the content of microcapsules, indicating that the microcapsules acted as moisture barriers. After being incorporated, chitosan-microcapsules/starch blend film shows a sustained drug release. The extent of the film degradation and microcapsules swelling in the release system indicated that the drug released of the blend film was pH sensitive. The blend film exhibited pharmacodynamic efficacy because of the efficient drug releasing. PMID- 26902893 TI - Solid state synthesis of starch-capped silver nanoparticles. AB - The present research addresses the establishment of a technique which is solely devoted to environmentally friendly one-pot green synthesis of dry highly stable powdered silver nanoparticles (AgNPs) using starch as both reductant and stabilizing agent in the presence of sodium hydroxide. It is believed that the sodium hydroxide can improve the reduction potential of starch. Thus when the alkali treated starch is submitted to addition of silver nitrate (AgNO3), the alkali treated starch induces the well-established dual role of starch; reduction of silver ions (Ag(+)) to AgNPs and capping the as-formed AgNPs to prevent them from further growth and agglomeration. Beside assessment of AgNPs formation, structural and morphological characteristics of AgNPs are investigated by making use of UV-vis spectroscopy, transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential, FT-IR and X-ray diffraction (XRD) analysis. Research outputs signify (a) the absorbance around 410-420nm in the UV-vis spectra of AgNPs appears most, probably owing to the presence of nanosized silver particles and the intensity of this peak increases by increasing AgNO3 concentration; (b) that highly stable AgNPs with well-dispersed particle are successfully prepared using the present research-based innovation; (c) that the size of AgNPs does not exceed 30nm with sphere-like morphology even at the highest Ag(+) concentration employed during synthesis operation; (d) that the XRD and FT-IR confirm the successful preparation of pure AgNPs without noticeable impurities; (d) and that the one-pot synthesis of powdered AgNPs in large scale is clean and easily operated and easily transportation which may be applied as per demands of industries such as textile and painting industry. PMID- 26902894 TI - Antimicrobial eugenol nanoemulsion prepared by gum arabic and lecithin and evaluation of drying technologies. AB - The purpose of present work was to develop eugenol oil nanoemulsions using gum arabic and lecithin as food grade natural emulsifiers, and study their antimicrobial activity. In addition, our study also evaluated different drying techniques (spray drying and freeze drying) on the morphology and redispersibility of nanoemulsion powders. The optimal fabrication method, physicochemical and structural characterization, stability, and antimicrobial activity were investigated. Results showed that nanoemusions with a particle size of 103.6+/-7.5nm were obtained by mixing aqueous phase (0.5% gum arabic, 0.5% lecithin, w/v) and eugenol oil (1.25%, w/v), which was premixed with ethanol (as a co-surfactant), followed by high speed homogenization process. The molecular interactions among emulsifiers and eugenol were evidenced by Fourier transform infrared spectroscopy. Buchi B-90 Nano Spray Dryer was evaluated as a powerful tool to obtain ultrafine spherical powders with a size of less than 500nm, compared to flake-like aggregation obtained by freeze-drying. The dried powders exhibited excellent re-dispersibility in water and maintained their physicochemical properties after re-hydration. The nanoemulsions did not adversely affect the antimicrobial activity of eugenol against Listeria monocytogenes and Salmonella Enteritidis. Therefore, the nanoemulsions have the potential to be applied in the food industry as a food preservative or sanitizer. PMID- 26902895 TI - The antiviral potency of Fagus sylvatica 4OMe-glucuronoxylan sulfates. AB - Herpes simplex virus belongs to Herpesviridae family and causes infection of humans from ancient times. 4OMe-glucuronoxylans as the renewable biopolymers can be promising glycomaterials for various applications in pharmacy. Control enzymatic degradation of the native 4OMe-glucuronoxylan (GX1) followed by targeted sulfation procedure afforded a range of 4OMe-glucuronoxylan sulfates differed in the degree of sulfation (10-16%) and molecular mass (21,000 5000g/mol; GXS1>GXS2>GXS3>GXS4). Antiviral activity tests on GXS1-4 against herpes simplex virus (HSV) types 1 and 2 revealed the positive effect of all compounds against strains of herpes virus. Of them, the compounds GXS1 and GXS4 were shown to be the most active for both HSV serotypes. The antiviral activity of GXS1 and GXS4 was similar to those of heparin or dextran sulfate, used as reference compounds. It was found that GXS1 and GXS4 were active as well against Polio and dengue viruses, however, on a smaller scale. The mode of antiviral action of 4OMe-glucuronoxylan sulfates is due to inhibition of the virus binding to the cell receptors. PMID- 26902897 TI - Clean graphene interfaces by selective dry transfer for large area silicon integration. AB - Here we present a very fast, selective mechanical approach for transferring graphene with low levels of copper contamination from seed wafers on which it was grown to target wafers for very large scale integration (VLSI) electronics. We found that graphene/copper or copper/silicon oxide delamination paths could be selected by slow and faster separation rates, respectively. Thus graphene can be transferred to a target wafer, either exposed or protected by the seed copper layer, which can later be removed by etching. Delamination paths were identified by SEM and Raman spectroscopy. The sheet resistance of the graphene produced by the two approaches was slightly higher than graphene transferred by a PMMA wet transfer process, indicating reduced impurity doping, and the variation in the sheet resistance values was much lower. Copper contamination levels, quantitatively established by TOF-SIMS, were several orders of magnitude lower than the values for PMMA assisted transfer. In addition, we demonstrated that top gated transistor devices from our mechanical, delamination transferred graphene exhibited superior transistor behavior to PMMA-assisted wet transfer graphene. The adhesion energy, strength and range of the interactions were quantitatively determined by nonlinear fracture analyses, and suggest that the roughness of the interface between graphene and copper plays an important role with implications for improvements in manufacturing processes. PMID- 26902896 TI - Improved capacitive deionization performance of mixed hydrophobic/hydrophilic activated carbon electrodes. AB - Capacitive deionization (CDI) is a promising salt removal technology with high energy efficiency when applied to low molar concentration aqueous electrolytes. As an interfacial process, ion electrosorption during CDI operation is sensitive to the pore structure and the total pore volume of carbon electrodes limits the maximum salt adsorption capacity (SAC). Thus, activation of carbons as a widely used method to enhance the porosity of a material should also be highly attractive for improving SAC values. In our study, we use easy-to-scale and facile-to-apply CO2-activation at temperatures between 950 degrees C and 1020 degrees C to increase the porosity of commercially available activated carbon. While the pore volume and surface area can be significantly increased up to 1.51 cm(3) g(-1) and 2113 m(2) g(-1), this comes at the expense of making the carbon more hydrophobic. We present a novel strategy to capitalize on the improved pore structure by admixing as received (more hydrophilic) carbon with CO2-treated (more hydrophobic) carbon for CDI electrodes without using membranes. This translates into an enhanced charge storage ability in high and low molar concentrations (1 M and 5 mM NaCl) and significantly improved CDI performance (at 5 mM NaCl). In particular, we obtain stable CDI performance at 0.86 charge efficiency with 13.1 mg g(-1) SAC for an optimized 2:1 mixture (by mass). PMID- 26902898 TI - Flexibility and disorder in metal-organic frameworks. PMID- 26902899 TI - High-throughput allogeneic antibody detection using protein microarrays. AB - Enzyme-linked immunosorbent assays (ELISAs) have traditionally been used to detect alloantibodies in patient plasma samples post hematopoietic cell transplantation (HCT); however, protein microarrays have the potential to be multiplexed, more sensitive, and higher throughput than ELISAs. Here, we describe the development of a novel and sensitive microarray method for detection of allogeneic antibodies against minor histocompatibility antigens encoded on the Y chromosome, called HY antigens. Six microarray surfaces were tested for their ability to bind recombinant protein and peptide HY antigens. Significant allogeneic immune responses were determined in male patients with female donors by considering normal male donor responses as baseline. HY microarray results were also compared with our previous ELISA results. Our overall goal was to maximize antibody detection for both recombinant protein and peptide epitopes. For detection of HY antigens, the Epoxy (Schott) protein microarray surface was both most sensitive and reliable and has become the standard surface in our microarray platform. PMID- 26902900 TI - Influence of Mycotoxin Binders on the Oral Bioavailability of Doxycycline in Pigs. AB - Mycotoxin binders are feed additives that aim to adsorb mycotoxins in the gastrointestinal tract of animals, making them unavailable for systemic absorption. The antimicrobial drug doxycycline (DOX) is often used in pigs and is administered through feed or drinking water; hence, DOX can come in contact with mycotoxin binders in the gastrointestinal tract. This paper describes the effect of four mycotoxin binders on the absorption of orally administered DOX in pigs. Two experiments were conducted: The first used a setup with bolus administration to fasted pigs at two different dosages of mycotoxin binder. In the second experiment, DOX and the binders were mixed in the feed at dosages recommended by the manufacturers (= field conditions). Interactions are possible between some of the mycotoxin binders dosed at 10 g/kg feed but not at 2 g/kg feed. When applying field conditions, no influences were seen on the plasma concentrations of DOX. PMID- 26902901 TI - Graphene oxide/metal nanocrystal multilaminates as the atomic limit for safe and selective hydrogen storage. AB - Interest in hydrogen fuel is growing for automotive applications; however, safe, dense, solid-state hydrogen storage remains a formidable scientific challenge. Metal hydrides offer ample storage capacity and do not require cryogens or exceedingly high pressures for operation. However, hydrides have largely been abandoned because of oxidative instability and sluggish kinetics. We report a new, environmentally stable hydrogen storage material constructed of Mg nanocrystals encapsulated by atomically thin and gas-selective reduced graphene oxide (rGO) sheets. This material, protected from oxygen and moisture by the rGO layers, exhibits exceptionally dense hydrogen storage (6.5 wt% and 0.105 kg H2 per litre in the total composite). As rGO is atomically thin, this approach minimizes inactive mass in the composite, while also providing a kinetic enhancement to hydrogen sorption performance. These multilaminates of rGO-Mg are able to deliver exceptionally dense hydrogen storage and provide a material platform for harnessing the attributes of sensitive nanomaterials in demanding environments. PMID- 26902902 TI - Usefulness of silkworm as a host animal for understanding pathogenicity of Cryptococcus neoformans. AB - We propose Cryptococcus neoformans infection model using silkworm for understanding cryptococcosis and screening of therapeutically effective antibiotics. Silkworm is an insect whose rearing methods were established through a long history of the sericulture industry. Silkworm facilitates experiments using a large number of individuals because of low cost for rearing and few ethical problems caused by killing animals. Silkworm can be reared at 37C to perform infection experiments at same temperature to human body. Injection of accurate amounts of samples into hemolymph of silkworm by usual syringes is easy to be done since silkworm has an appropriate size to handle. Moreover two injection methods, injection into hemolymph and intestine, are distinguishable for silkworms. The former is correspondent to intravenous injection, and the latter is to oral administration in humans. Taking these advantages of silkworms as host animals, it is possible to evaluate the virulence factors in C. neoformans and the therapeutic efficacy of antifungal agents. PMID- 26902903 TI - Angiogenesis in refractory depression: A possible phenotypic target to avoid the blood brain barrier. AB - Major depressive syndrome (so-called depression) is a common but serious mental disease that causes low mood. Most patients are treatable, mainly because of high response rates for medicines such as selective serotonin-reuptake inhibitors (SSRIs). However, there are still a considerable number of patients with refractory or drug-resistant depression. On the other hand, recent findings suggest that angiogenesis, i.e., making new blood vessels, could have an important role in the recovery from depressive disorders, at least in part. It has been reported that the brain capillaries are physiologically capable of undergoing angiogenesis upon stimuli such as exercise and SSRIs seem to accelerate brain angiogenesis. Drugs targeting angiogenesis may possibly be another good concept. In addition, the blood brain barrier (BBB), which is a major obstacle for drug development for the central nervous system, would be circumvented. Here I summarize the reports that relate angiogenesis to a cure for major depression and discuss some of the potential molecular targets. PMID- 26902904 TI - A hyperglycemic silkworm model for evaluating hypoglycemic activity of Rehmanniae Radix, an herbal medicine. AB - Silkworm shows hyperglycemia after intake of diet containing large amount of glucose. The hyperglycemic silkworm model is useful for evaluation of anti diabetic drugs. A hot water extract of Rehmanniae Radix, an herbal medicine, showed hypoglycemic effect against the hyperglycemic silkworms. This method is applicable for quick and simple evaluation of the hypoglycemic activities of different batches of Rehmanniae Radix. Our findings suggest that silkworms have a lot of merit as experimental animals for evaluation of various herbal medicines. PMID- 26902906 TI - Functionalized graphene oxide quantum dot-PVA hydrogel: a colorimetric sensor for Fe2+, Co2+ and Cu2+ ions. AB - Functionalized graphene oxide quantum dots (GOQDs)-poly(vinyl alcohol) (PVA) hybrid hydrogels were prepared using a simple, facile and cost-effective strategy. GOQDs bearing different surface functional groups were introduced as the cross-linking agent into the PVA matrix thereby resulting in gelation. The four different types of hybrid hydrogels were prepared using graphene oxide, reduced graphene oxide, ester functionalized graphene oxide and amine functionalized GOQDs as cross-linking agents. It was observed that the hybrid hydrogel prepared with amine functionalized GOQDs was the most stable. The potential applicability of using this solid sensing platform has been subsequently explored in an easy, simple, effective and sensitive method for optical detection of M(2+) (Fe(2+), Co(2+) and Cu(2+)) in aqueous media involving colorimetric detection. Amine functionalized GOQDs-PVA hybrid hydrogel when put into the corresponding solution of Fe(2+), Co(2+) and Cu(2+) renders brown, orange and blue coloration respectively of the solution detecting the presence of Fe(2+), Co(2+) and Cu(2+) ions in the solution. The minimum detection limit observed was 1 * 10(-7) M using UV-visible spectroscopy. Further, the applicability of the sensing material was also tested for a mixture of co existing ions in solution to demonstrate the practical applicability of the system. Insight into the probable mechanistic pathway involved in the detection process is also being discussed. PMID- 26902905 TI - [Mobile geriatric rehabilitation in statutory health insurance: Conceptual strategy and results of a nationwide treatment documentation (Part 1)]. AB - BACKGROUND: Insurants have a statutory right to mobile rehabilitation in which a multidisciplinary team carries out treatment in the familiar home environment. Framework recommendations in geriatric medicine were presented by the statutory health insurance (SHI) and a standardized treatment documentation was implemented nationwide. OBJECTIVE: This article presents the conceptual design and selected results from this treatment documentation and reports on the established practice. MATERIAL AND METHODS: A total of 1879 anonymized cases of mobile geriatric rehabilitation carried out between 2011 and 2014 from 11 participating institutions were analyzed with respect to patient and process-related features. RESULTS: The patients were on average 81 years old and 61 % were female. The mobile rehabilitation was provided on average over 22 treatment days over a period of 8 weeks and in 84 % of cases following hospital treatment. Of the rehabilitation patients 27 % lived in a care home prior to treatment and 73 % were already allocated to a care level. The statistically significant gain in capacity for self-sufficiency was 18 points on the Barthel index at the end of the rehabilitation. The majority of treatment was provided by physiotherapists and occupational therapists followed by speech therapists and nursing personnel. Relevant differences were detected between the institutions regarding the indications, access route, therapy combinations, treatment frequency, scope and duration. At the same time individual requirements from the framework recommendations were sometimes not met. CONCLUSION: Even though the treatment documentation does not replace any external mobile rehabilitation quality assurance, it provides transparency in a still very limited range of services that are sometimes differently implemented at institutions. It therefore provides the basis for further development of mobile out-patient rehabilitation in SHI. PMID- 26902907 TI - Piperine containing floating microspheres: an approach for drug targeting to the upper gastrointestinal tract. AB - The purpose of this investigation was to prepare and characterize acyclovir loaded floating microspheres by emulsification solvent evaporation method. Piperine was added to investigate its effect on acyclovir bioavailability. The microspheres were characterized for size, shape, entrapment efficiency, in vitro drug release, and in vivo pharmacokinetic parameters. The morphological characterization of microspheres was done using a scanning electron microscope. The microspheres were spherical and had particle size in the range of 400 to 525 MUm. The percent drug entrapment efficiency varied between 56.12 +/- 1.32 % to 87.32 +/- 5.28 %. The drug release was decreased at higher polymer concentrations. Nearly two times higher AUC0-24 value of acyclovir-loaded piperine containing microspheres (15614.13 +/- 6953.13 ng h ml(-1)) was observed as compared to the drug solution (7552.33 +/- 3219.09 ng h ml(-1)). Under the accelerated storage conditions, the best selected formulation was found to be stable for 90 days. The preliminary results of this study suggest that the developed microspheres containing acyclovir could enhance drug entrapment efficiency, reduce initial burst release, and prolong the drug release with enhanced bioavailability. PMID- 26902908 TI - Aquabirnavirus polyploidy: A new strategy to modulate virulence? AB - One of the main research issues regarding the infectious pancreatic necrosis virus (IPNV) is its virulence mechanisms. The bases for understanding the molecular virulence determinants of this virus were established over the last decade when it was demonstrated that certain aa domains in the VP2 and VP2-NS inter-region determined the level of virulence of IPNV. However, certain variability was still inexplicable and, therefore, other factors might also have been involved. To this regard, it has recently been demonstrated that the infectious bursal disease virus (IBDV), a virus of a different genus of the same family as IPNV, can package more than 2 dsRNA segments, and that polyploidy may be associated to virulence. In the present report, we analyze the viral fractions obtained after gradient centrifugation to demonstrate that IPNV virions can also package more than 2 segments, thus indicating that polyploidy is a common birnavirus trait. The differential replication ex vivo and virulence in vivo additionally suggest that such a characteristic is involved in the modulation of viral infectivity. However, although the ex vivo results clearly demonstrated that the replication capacity is enhanced as the viral ploidy increases, the in vivo results could not strongly support a direct relationship between ploidy and virulence to the host, thus suggesting that other virulence determinants are also involved. PMID- 26902909 TI - Biochemical Characterization of Kat1: a Domesticated hAT-Transposase that Induces DNA Hairpin Formation and MAT-Switching. AB - Kluyveromyces lactis hAT-transposase 1 (Kat1) generates hairpin-capped DNA double strand breaks leading to MAT-switching (MATa to MATalpha). Using purified Kat1, we demonstrate the importance of terminal inverted repeats and subterminal repeats for its endonuclease activity. Kat1 promoted joining of the transposon end into a target DNA molecule in vitro, a biochemical feature that ties Kat1 to transposases. Gas-phase Electrophoretic Mobility Macromolecule analysis revealed that Kat1 can form hexamers when complexed with DNA. Kat1 point mutants were generated in conserved positions to explore structure-function relationships. Mutants of predicted catalytic residues abolished both DNA cleavage and strand transfer. Interestingly, W576A predicted to be impaired for hairpin formation, was active for DNA cleavage and supported wild type levels of mating-type switching. In contrast, the conserved CXXH motif was critical for hairpin formation because Kat1 C402A/H405A completely blocked hairpinning and switching, but still generated nicks in the DNA. Mutations in the BED zinc-finger domain (C130A/C133A) resulted in an unspecific nuclease activity, presumably due to nonspecific DNA interaction. Kat1 mutants that were defective for cleavage in vitro were also defective for mating-type switching. Collectively, this study reveals Kat1 sharing extensive biochemical similarities with cut and paste transposons despite being domesticated and evolutionary diverged from active transposons. PMID- 26902910 TI - Entanglement dynamics of Nitrogen-vacancy centers spin ensembles coupled to a superconducting resonator. AB - Exploration of macroscopic quantum entanglement is of great interest in both fundamental science and practical application. We investigate a hybrid quantum system that consists of two nitrogen-vacancy centers ensembles (NVE) coupled to a superconducting coplanar waveguide resonator (CPWR). The collective magnetic coupling between the NVE and the CPWR is employed to generate macroscopic entanglement between the NVEs, where the CPWR acts as the quantum bus. We find that, this NVE-CPWR hybrid system behaves as a system of three coupled harmonic oscillators, and the excitation prepared initially in the CPWR can be distributed into these two NVEs. In the nondissipative case, the entanglement of NVEs oscillates periodically and the maximal entanglement always keeps unity if the CPWR is initially prepared in the odd coherent state. Considering the dissipative effect from the CPWR and NVEs, the amount of entanglement between these two NVEs strongly depends on the initial state of the CPWR, and the maximal entanglement can be tuned by adjusting the initial states of the total system. The experimental feasibility and challenge with currently available technology are discussed. PMID- 26902911 TI - Rin1 restores host phagocytic activity during invasion by Pseudomonas aeruginosa. AB - Pseudomonas aeruginosa uses a type III secretion system to deliver toxic effector proteins directly into host cells and alter host protein functions. Exoenzyme S (ExoS), a type III effector protein, ADP-ribosylates Rab5 GTPase and impairs early phagocytic events in macrophage cells. In this study, we tested the hypothesis that Rin1, a Ras effector protein and Rab5 guanine nucleotide exchange factor, generates an intrinsic Rab5 activity cycle during phagocytosis of live P. aeruginosa; thus, allowing proper phagocytic killing. We found that Rab5 activity was attenuated at a very early time point (2.5 min) of the phagocytic process of live but not of heat-inactivated P. aeruginosa. However, upon overexpressing Rin1 in macrophages, the Rab5 activity sustained for a prolonged time (~20 min) counteracting the negative effects during phagocytosis of live P. aeruginosa. Ras, also a substrate of the ADP-ribosyltransferase activity of ExoS, remained active during the early events of phagocytosis of live as well as heat inactivated P. aeruginosa. Further examinations revealed that the Rin1 : Vps9 domain (the Rab5 nucleotide catalytic domain) and the Rin1 : RA domain (the Ras association domain of Rin1) are both required for optimal Rin1 function. Finally, the time-based analysis of the ADP-ribosylation status of Rab5 and Ras obtained from this study was consistent in the context of the regulation of (i) Rab5 activity by Rin1 : Vps9 domain and (ii) Ras interaction with Rin1 via the Rin1 : RA domain. These observations highlight a novel crosstalk between Rin1-Rab5 and Rin1-Ras complexes that offsets the anti-phagocytic effects of ExoS in macrophages. PMID- 26902912 TI - Laetoli's lost tracks: 3D generated mean shape and missing footprints. AB - The Laetoli site (Tanzania) contains the oldest known hominin footprints, and their interpretation remains open to debate, despite over 35 years of research. The two hominin trackways present are parallel to one another, one of which is a composite formed by at least two individuals walking in single file. Most researchers have focused on the single, clearly discernible G1 trackway while the G2/3 trackway has been largely dismissed due to its composite nature. Here we report the use of a new technique that allows us to decouple the G2 and G3 tracks for the first time. In so doing we are able to quantify the mean footprint topology of the G3 trackway and render it useable for subsequent data analyses. By restoring the effectively 'lost' G3 track, we have doubled the available data on some of the rarest traces directly associated with our Pliocene ancestors. PMID- 26902913 TI - Bayesian population reconstruction of female populations for less developed and more developed countries. AB - We show that Bayesian population reconstruction, a recent method for estimating past populations by age, works for data of widely varying quality. Bayesian reconstruction simultaneously estimates age-specific population counts, fertility rates, mortality rates, and net international migration flows from fragmentary data, while formally accounting for measurement error. As inputs, Bayesian reconstruction uses initial bias-reduced estimates of standard demographic variables. We reconstruct the female populations of three countries: Laos, a country with little vital registration data where population estimation depends largely on surveys; Sri Lanka, a country with some vital registration data; and New Zealand, a country with a highly developed statistical system and good quality vital registration data. In addition, we extend the method to countries without censuses at regular intervals. We also use it to assess the consistency of results between model life tables and available census data, and hence to compare different model life table systems. PMID- 26902914 TI - Diagnostic Accuracy of Cone-beam Computed Tomography and Conventional Radiography on Apical Periodontitis: A Systematic Review and Meta-analysis. AB - INTRODUCTION: Endodontic diagnosis depends on accurate radiographic examination. Assessment of the location and extent of apical periodontitis (AP) can influence treatment planning and subsequent treatment outcomes. Therefore, this systematic review and meta-analysis assessed the diagnostic accuracy of conventional radiography and cone-beam computed tomographic (CBCT) imaging on the discrimination of AP from no lesion. METHODS: Eight electronic databases with no language or time limitations were searched. Articles in which the primary objective was to evaluate the accuracy (sensitivity and specificity) of any type of radiographic technique to assess AP in humans were selected. The gold standard was the histologic examination for actual AP (in vivo) or in situ visualization of bone defects for induced artificial AP (in vitro). Accuracy measurements described in the studies were transformed to construct receiver operating characteristic curves and forest plots with the aid of Review Manager v.5.2 (The Nordic Cochrane Centre, Copenhagen, Denmark) and MetaDisc v.1.4. software (Unit of Clinical Biostatistics Team of the Ramon y Cajal Hospital, Madrid, Spain). The methodology of the selected studies was evaluated using the Quality Assessment Tool for Diagnostic Accuracy Studies-2. RESULTS: Only 9 studies met the inclusion criteria and were subjected to a qualitative analysis. A meta-analysis was conducted on 6 of these articles. All of these articles studied artificial AP with induced bone defects. The accuracy values (area under the curve) were 0.96 for CBCT imaging, 0.73 for conventional periapical radiography, and 0.72 for digital periapical radiography. No evidence was found for panoramic radiography. CONCLUSIONS: Periapical radiographs (digital and conventional) reported good diagnostic accuracy on the discrimination of artificial AP from no lesions, whereas CBCT imaging showed excellent accuracy values. PMID- 26902916 TI - Nanopatterned polymer brushes by reactive writing. AB - Polymer brush patterns were prepared by a combination of electron beam induced damage in self-assembled monolayers (SAMs), creating a stable carbonaceous deposit, and consecutive self-initiated photografting and photopolymerization (SIPGP). This newly applied technique, reactive writing (RW), is investigated with 1H,1H,2H,2H-perfluorooctyltriethoxysilane SAM (PF-SAM) on silicon oxide, which, when modified by RW, can be selectively functionalized by SIPGP. With the monomer N,N-dimethylaminoethyl methacrylate (DMAEMA), we demonstrate the straightforward formation of polymer brush gradients and single polymer lines of sub-100 nm lateral dimensions, with high contrast to the PF-SAM background. The lithography parameters acceleration voltage, irradiation dose, beam current and dwell time were systematically varied to identify the optimal conditions for the maximum conversion of the SAM into a carbonaceous deposit. The results of this approach were compared to patterns prepared by carbon templating (CT) under analogous conditions, revealing a dwell time dependency, which differs from earlier reports. This new technique expands the range of CT by giving the opportunity to not only vary the chemistry of the created polymer patterns with monomer choice but also vary the chemistry of the surrounding substrate. PMID- 26902915 TI - Affiliation, reward, and immune biomarkers coalesce to support social synchrony during periods of bond formation in humans. AB - Social bonds are critical for survival and adaptation and periods of bond formation involve reorganization of neurobiological systems as mediated by social behavior. Theoretical accounts and animal studies suggest similarity between parent-infant and pair bonding, a hypothesis not yet directly tested in humans. In this study, we recruited three groups of human adults (N=189); parents who had their firstborn child in the last 4-6months, new lovers who began a romantic relationship within the past 4months, and non-attached singles. We measured plasma oxytocin (OT), beta endorphin (beta-End), and interlukin-6 (IL-6), biomarkers of the affiliation, reward, and stress-response systems, and micro coded gaze and affect synchrony between parents and infants and among new lovers during social interaction. OT significantly increased during periods of parental and romantic bonding and was highest in new lovers. In contrast, IL-6 and beta End were highest in new parents and lowest in singles. Biomarkers became more tightly coupled during periods of bond formation and inter-correlation among hormones was highest during romantic bonding. Structural equation modeling indicated that the effects of IL-6 and beta-End on behavioral synchrony were mediated by their impact on OT, highlighting the integrative role of the oxytocinergic system in supporting human social affiliation. Findings suggest that periods of bond formation are accompanied by increased activity, as well as tighter cross-talk among systems underpinning affiliation, reward, and stress management and that research on the multidimensional process of bonding may shed further light on the effects of attachment on health. PMID- 26902918 TI - Capacitive mixing with electrodes of the same kind for energy production from salinity differences. AB - The capacitive mixing technique is aimed at producing renewable energy from salinity differences, for example between sea and river water. The technique makes use of two electrodes that modify their potential in opposite directions when the concentration of the solution in which they are immersed is changed, as a consequence of the dynamics of the electric double layer which forms in the ionic solution. Unfortunately, it is difficult to find two electrodes presenting both optimal performances and opposite potential variations. In order to overcome this problem, we present here a cell scheme with electrodes of the same kind (and thus identical dependence of potential on concentration) which can be operated with a CapMix cycle; it is based on a concentration cell with identical electrodes dipped into two compartments separated by a non-perm-selective porous diaphragm. Thanks to the cyclic operation, the actual cell voltage rise and the power production are close to the values obtained with the traditional scheme, or even higher, depending on the features of the ion transport in the liquid junction region. We present an experimental demonstration of the working principles and we study the power production and energy efficiency in the light of the theory of ion transport in fluids. We show that our technique is competitive with respect to the other CapMix techniques, with the relevant advantage that we make use of only one kind of electrode. PMID- 26902919 TI - Radiofrequency pulse design with numerical optimization in the Fourier domain. AB - OBJECTIVE AND METHODS: A radiofrequency (RF) pulse design technique is presented that uses iterative constrained minimization to determine Fourier domain coefficients for an optimal time domain RF pulse. The design of new RF pulses is especially beneficial for field strengths of 7.0 T and above, where challenges pertaining to specific absorption rate (SAR) are exacerbated. RESULTS AND CONCLUSION: A pair of 90 degrees and 180 degrees spin-echo pulses was designed to lower SAR without the need for a variable slice gradient. The optimized pulses were deployed to a 7.0 T human scanner to demonstrate a reduction in SAR while retaining signal-to-noise (SNR) ratio. PMID- 26902920 TI - Autosomal Recessive Hypotrichosis with Woolly Hair Caused by a Mutation in the Keratin 25 Gene Expressed in Hair Follicles. AB - Hypotrichosis is an abnormal condition characterized by decreased hair density and various defects in hair structure and growth patterns. In particular, in woolly hair, hypotrichosis is characterized by a tightly curled structure and abnormal growth. In this study, we present a detailed comparative examination of individuals affected by autosomal-recessive hypotrichosis (ARH), which distinguishes two types of ARH. Earlier, we demonstrated that exon 4 deletion in the lipase H gene caused an ARH (hypotrichosis 7; MIM: 604379) in populations of the Volga-Ural region of Russia. Screening for this mutation in all affected individuals revealed its presence only in the group with the hypotrichosis 7 phenotype. Other patients formed a separate group of woolly hair-associated ARH, with a homozygous missense mutation c.712G>T (p.Val238Leu) in a highly conserved position of type I keratin KRT25 (K25). Haplotype analysis indicated a founder effect. An expression study in the HaCaT cell line demonstrated a deleterious effect of the p.Val238Leu mutation on the formation of keratin intermediate filaments. Hence, we have identified a previously unreported missense mutation in the KRT25 gene causing ARH with woolly hair. PMID- 26902921 TI - beta-Catenin Stabilization in Skin Fibroblasts Causes Fibrotic Lesions by Preventing Adipocyte Differentiation of the Reticular Dermis. AB - The Wnt/beta-catenin pathway plays a central role in epidermal homeostasis and regeneration, but how it affects fibroblast fate decisions is unknown. We investigated the effect of targeted beta-catenin stabilization in dermal fibroblasts. Comparative gene expression profiling of stem cell antigen 1(-) (Sca1(-)) and Sca1(+) neonatal fibroblasts from upper and lower dermis, respectively, confirmed that Sca1(+) cells had a preadipocyte signature and showed differential expression of Wnt/beta-catenin-associated genes. By targeting all fibroblasts or selectively targeting Dlk1(+) lower dermal fibroblasts, we found that beta-catenin stabilization between developmental stages E16.5 and P2 resulted in a reduction in the dermal adipocyte layer with a corresponding increase in dermal fibrosis and an altered hair cycle. The fibrotic phenotype correlated with a reduction in the potential of Sca1(+) fibroblasts to undergo adipogenic differentiation ex vivo. Our findings indicate that Wnt/beta-catenin signaling controls adipogenic cell fate within the lower dermis, which potentially contributes to the pathogenesis of fibrotic skin diseases. PMID- 26902922 TI - Yes-Associated Protein Contributes to the Development of Human Cutaneous Squamous Cell Carcinoma via Activation of RAS. AB - Cutaneous squamous cell carcinoma (cSCC) is one of the most common skin malignant tumors with an increasing incidence. Studies have shown that Yes-associated protein (YAP) participates in the development of a variety of tumors as an oncogene, but to our knowledge its role in cSCC has not been reported. In this study, we used immunohistochemistry to show that YAP expression was elevated in cSCC samples of different stages versus in normal skin and that it was well correlated with the progression of the disease. Down-regulation of YAP in cSCC cell lines A431 and SCL-1 inhibited cell proliferation by inducing growth arrest during the G1/S phase transition, promoted apoptosis, and reduced invasion and migration abilities in vitro. Conversely, overexpression of YAP promoted cell proliferation and protected cells against basal and chemotherapy-induced apoptosis. These oncogenic effects of YAP were associated with activation of the RAS protein and its downstream AKT and ERK. Using a mouse xenograft model, we further showed that YAP depletion inhibited cSCC tumor growth in vivo. Our results suggested that YAP is involved in the carcinogenesis and development of cSCC and that it may serve as a biomarker or therapeutic target of this disease. PMID- 26902923 TI - The Growing Burden of Invasive Melanoma: Projections of Incidence Rates and Numbers of New Cases in Six Susceptible Populations through 2031. AB - New melanoma therapies are being developed rapidly, complementing prevention and detection strategies for disease control. Estimating the future burden of melanoma is necessary for deciding how best to deploy limited resources to achieve effective melanoma control. Using three decades of cancer registry data (1982-2011) from six populations with moderate to high melanoma incidence (US whites and the populations of the United Kingdom, Sweden, Norway, Australia, New Zealand), we applied age-period-cohort models to describe current trends and project future incidence rates and numbers of melanomas out to 2031. Between 1982 and 2011, melanoma rates in US whites, and the populations of the United Kingdom, Sweden, and Norway increased at more than 3% annually and are projected to continue rising until at least 2022. Melanoma incidence in Australia has been declining since 2005 (-0.7% per year), and melanoma incidence in New Zealand is increasing but is projected to decline soon. The numbers of new melanoma cases will rise in all six populations because of aging populations and high age specific rates in the elderly. In US whites, annual new cases will rise from around 70,000 in 2007-2011 to 116,000 in 2026-2031, with 79% of the increase attributable to rising age-specific rates and 21% to population growth and aging. The continued increases in case numbers in all six populations through 2031 will increase the challenges of melanoma control. PMID- 26902925 TI - 3D Printed Silicone-Hydrogel Scaffold with Enhanced Physicochemical Properties. AB - Scaffolds with multiple functionalities have attracted widespread attention in the field of tissue engineering due to their ability to control cell behavior through various cues, including mechanical, chemical, and electrical. Fabrication of such scaffolds from clinically approved materials is currently a huge challenge. The goal of this work was to fabricate a tissue engineering scaffold from clinically approved materials with the capability of delivering biomolecules and direct cell fate. We have used a simple 3D printing approach, that combines polymer casting with supercritical fluid technology to produce 3D interpenetrating polymer network (IPN) scaffold of silicone-poly(2-hydroxyethyl methacrylate)-co-poly(ethylene glycol) methyl ether acrylate (pHEMA-co-PEGMEA). The pHEMA-co-PEGMEA IPN materials were employed to support growth of human mesenchymal stem cells (hMSC), resulting in high cell viability and metabolic activity over a 3 weeks period. In addition, the IPN scaffolds support 3D tissue formation inside the porous scaffold with well spread cell morphology on the surface of the scaffold. As a proof of concept, sustained doxycycline (DOX) release from pHEMA-co-PEGMEA IPN was demonstrated and the biological activity of released drug from IPN was confirmed using a DOX regulated green fluorescent reporter (GFP) gene expression assay with HeLa cells. Given its unique mechanical and drug releasing characteristics, IPN scaffolds may be used for directing stem cell differentiation by releasing various chemicals from its hydrogel network. PMID- 26902926 TI - Comparison of outcome and interventional complication rate in patients with acute stroke treated with mechanical thrombectomy with and without bridging thrombolysis. AB - BACKGROUND: No randomized trial has investigated the effect of mechanical thrombectomy (MT) alone in patients with acute stroke. There are conflicting results as to whether prior intravenous thrombolysis (IVT) facilitates subsequent MT, and data in patients treated with MT alone owing to contraindications to IVT are limited. OBJECTIVE: To compare consecutive patients treated with MT alone or with preceding IVT in a large tertiary neurointerventional center, with special emphasis on contraindications to IVT. METHODS: Retrospective analysis of 283 consecutive patients with acute ischemic stroke treated with MT in a tertiary neurovascular center over 14 months. Data on characteristics of periprocedural times, recanalization rate, complications, and long-term functional outcome were collected prospectively. RESULTS: Information on prior IVT and functional outcome was available in 250 patients. Mean (SD) follow-up period was 5.7 (5.1) months and 105 (42%) patients received both IVT and MT. No significant differences were found in successful recanalization rates (Thrombolysis in Cerebral Infarction (TICI) 2b/3, 73.8% vs 73.1, p=0.952), complication rates, and long-term favorable outcome (modified Rankin Scale 0-2, 35.2% vs 40%, p=0.444) between patients receiving MT plus IVT and those receiving MT alone. A favorable outcome in patients directly treated with MT alone who were eligible for IVT was achieved in 48.2%. Thrombectomy was safe and resulted in a favorable outcome in 32% of patients with absolute contraindications to IVT. CONCLUSIONS: Preceding use of IVT was not an independent predictor of favorable outcome in patients with acute stroke treated with MT and complication rates did not differ whether or not IVT was used. MT is safe and achieved a favorable outcome in one-third of patients with stroke ineligible for IVT. PMID- 26902924 TI - Vector-free transmission and persistence of Japanese encephalitis virus in pigs. AB - Japanese encephalitis virus (JEV), a main cause of severe viral encephalitis in humans, has a complex ecology, composed of a cycle involving primarily waterbirds and mosquitoes, as well as a cycle involving pigs as amplifying hosts. To date, JEV transmission has been exclusively described as being mosquito-mediated. Here we demonstrate that JEV can be transmitted between pigs in the absence of arthropod vectors. Pigs shed virus in oronasal secretions and are highly susceptible to oronasal infection. Clinical symptoms, virus tropism and central nervous system histological lesions are similar in pigs infected through needle, contact or oronasal inoculation. In all cases, a particularly important site of replication are the tonsils, in which JEV is found to persist for at least 25 days despite the presence of high levels of neutralizing antibodies. Our findings could have a major impact on the ecology of JEV in temperate regions with short mosquito seasons. PMID- 26902927 TI - Inhibition of PA endonuclease activity of influenza virus RNA polymerase by Kampo medicines. AB - To find a novel influenza inhibitor targeting the endonuclease activity of influenza A virus polymerase acidic protein (PA), which is essential for the acquisition of primers for viral mRNA transcription, seven Kampo extracts were tested in vitro for their ability to inhibit endonuclease activity of the recombinant PA protein that was expressed and purified from Escherichia coli. The Kampo medicines Kakkonto, Shosaikoto, Saikokeishito, Keishito, Maobushisaishinto, and Maoto, but not Chikujountanto, inhibited PA endonuclease activity in a dose dependent manner. Our results indicate that Kampo medicines are good sources providing a structural lead for optimization of an influenza endonuclease inhibitor. PMID- 26902928 TI - Clonostachys rosea demethiolase STR3 controls the conversion of methionine into methanethiol. AB - Eukaryote-derived methioninase, catalyzing the one-step degradation of methionine (Met) to methanethiol (MTL), has received much attention for its low immunogenic potential and use as a therapeutic agent against Met-dependent tumors. Although biological and chemical degradation pathways for Met-MTL conversion are proposed, the concrete molecular mechanism for Met-MTL conversion in eukaryotes is still unclear. Previous studies demonstrated that alpha-keto-methylthiobutyric acid (KMBA), the intermediate for Met-MTL conversion, was located extracellularly and the demethiolase STR3 possessed no activities towards Met, which rule out the possibility of intracellular Met-MTL conversion pathway inside eukaryotes. We report here that degradation of Met resulted in intracellular accumulation of KMBA in Clonostachys rosea. Addition of Met to culture media led to the production of MTL and downregulation of STR3, while incubation of Met with surrogate substrate alpha-ketoglutaric acid enhanced the synthesis of MTL and triggered the upregulation of STR3. Subsequent biochemical analysis with recombinant STR3 showed that STR3 directly converted both Met and its transamination product KMBA to MTL. These results indicated that STR3 as rate limiting enzyme degrades Met and KMBA into MTL. Our findings suggest STR3 is a potential target for therapeutic agents against Met-dependent tumors and aging. PMID- 26902930 TI - Floating mechanism of a small liquid marble. AB - Flotation of small solid objects and liquid droplets on water is critical to natural and industrial activities. This paper reports the floating mechanism of liquid marbles, or liquid droplets coated with hydrophobic microparticles. We used X-ray computed tomography (XCT) to acquire cross-sectional images of the floating liquid marble and interface between the different phases. We then analysed the shape of the liquid marble and the angles at the three-phase contact line (TPCL). We found that the small floating liquid marbles follow the mechanism governing the flotation of solid objects in terms of surface tension forces. However, the contact angles formed and deformation of the liquid marble resemble that of a sessile liquid droplet on a thin, elastic solid. For small liquid marbles, the contact angle varies with volume due to the deformability of the interface. PMID- 26902929 TI - Reversal of epigenetic silencing of MHC class I chain-related protein A and B improves immune recognition of Merkel cell carcinoma. AB - Merkel cell carcinoma (MCC) is a virally associated cancer characterized by its aggressive behavior and strong immunogenicity. Both viral infection and malignant transformation induce expression of MHC class I chain-related protein (MIC) A and B, which signal stress to cells of the immune system via Natural Killer group 2D (NKG2D) resulting in elimination of target cells. However, despite transformation and the continued presence of virally-encoded proteins, MICs are only expressed in a minority of MCC tumors in situ and are completely absent on MCC cell lines in vitro. This lack of MIC expression was due to epigenetic silencing via MIC promoter hypo-acetylation; indeed, MIC expression was re-induced by pharmacological inhibition of histone deacetylases (HDACs) both in vitro and in vivo. This re-induction of MICs rendered MCC cells more sensitive to immune mediated lysis. Thus, epigenetic silencing of MICs is an important immune escape mechanism of MCCs. PMID- 26902931 TI - Insights into the gate of the nuclear pore complex. AB - Nuclear pore complexes (NPCs) serve as the gateway of the cell nucleus. These macromolecular assemblies form selective aqueous translocation channels permitting the free diffusion of small molecules, as well as receptor-mediated transport of large cargoes. Over the past decade, major progress has been made in both the structural determination of individual nucleoporins and subcomplexes by X-ray crystallography and in the structural analysis of the entire NPC by cryo electron tomography (cryo-ET). The metazoan NPC structure from Xenopus laevis oocytes was recently resolved up to 20 A by combining cryo-ET with advanced image processing techniques, revealing for the first time the architecture of the central channel. Here, we discuss the structure of the Xenopus laevis NPC and consider future perspectives that will eventually allow reconstructing the scaffold and gate of the NPC with higher resolution and identifying its transport relevant regions. This will eventually allow us to describe the structure of the NPC 'in action'. PMID- 26902932 TI - The zebrafish as a model to study intestinal inflammation. AB - Starting out as a model for developmental biology, during the last decade, zebrafish have also gained the attention of the immunologists and oncologists. Due to its small size, high fecundity and full annotation of its genome, the zebrafish is an attractive model system. The fact that fish are transparent early in life combined with the growing list of immune cell reporter fish, enables in vivo tracking of immune responses in a complete organism. Since zebrafish develop ex utero from a fertilized egg, immune development can be monitored from the start of life. Given that several gut functions and immune genes are conserved between zebrafish and mammals, the zebrafish is an interesting model organism to investigate fundamental processes underlying intestinal inflammation and injury. This review will first provide some background on zebrafish intestinal development, bacterial colonization and immunity, showing the similarities and differences compared to mammals. This will be followed by an overview of the existing models for intestinal disease, and concluded by future perspectives in light of the newest technologies and insights. PMID- 26902933 TI - Publication of Clinical Studies Supporting FDA Premarket Approval for High-Risk Cardiovascular Devices Between 2011 and 2013: A Cross-sectional Study. PMID- 26902934 TI - Double Barrel In Situ Recanalization of Thrombosed Nonretrievable IVC filter. AB - We report a case of endovascular recanalization of complete thrombotic occlusion of the inferior vena cava (IVC) and bilateral iliac veins using the architectural knowledge of the in situ permanent IVC filter in a 23-year-old male. The infrarenal permanent IVC filter was TRAPEASE permanent vena cava filter (Cordis) placed at an outstation hospital for pulmonary embolism. Being permanent variant of filter, percutaneous removal was not possible. The patient had severe venous claudication and an attempt to recanalize the blocked filter was considered, in view of the age no justifiable indication for a long-term filter. After pharmacomechanical catheter-directed thrombolysis, there was residual focal flow limiting thrombus within the filter. The design of the Trapease Cordis filter was instrumental in our decision to attempt to recanalize the filter in situ using 2 parallel stents with the filter struts as anchoring pillars in a double-barrel alignment. In similar cases of persistent Trapease filter-related thrombotic occlusion of the IVC, this double barrel in situ recanalization shall be a viable alternative to the well-described technique of crushing the filter and recanalizing it with a single stent. PMID- 26902935 TI - Clinical Agreement between Nurses in the Ultrasound Measurement of Abdominal Aortic Diameter within a National Screening Programme. AB - BACKGROUND: Accurate measurement is central to abdominal aortic aneurysm screening, but information concerning differences between observers using modern ultrasound devices is lacking. Our aim was to assess clinical agreement among nurses within a national screening programme. METHODS: Between-observer repeatability was assessed among 2 pairs of nurses (A & B and C & D) screening a consecutive series of men at a single-community clinic in Grampian, Scotland. All 4 nurses used the same ultrasound device (GE-LOGIQe 1.5-4.6 MHz curvilinear probe) to measure maximal infrarenal inner-to-inner (ITI) anteroposterior diameter in longitudinal and transverse planes. Nurses alternated in their measurements and were blinded to their partners' measurements. Participants remained supine while "double-scanned." Clinical agreement was assessed as twice the standard deviation (2 SD) of mean differences. Analysis was undertaken using IBM-SPSS-Statistics (version 22) using the Bland-Altman "limits of agreement" (95% LoA) approach (mean difference +/-2 SD) and related plots. RESULTS: A total of 63 consecutive men underwent assessment (30 men by nurses A & B; 33 men by nurses C & D). Mean age 65.5 years, brachial blood pressure 145/88 mm Hg, current smokers 14%, never smoked 41%, diabetic 18%, arterial disease 11%, daily aspirin 16%, antihypertensives 35%, and statin therapy 44%. Mean aortic diameter (ITI) was 1.81 centimeters (cm; range 1.28-2.45; SD 0.18). Pooled mean differences between nurses was 0.05 cm (95% confidence interval 0.02-0.08); 2 SD +/- 0.23 with 95% LoA -0.18 to 0.28 cm. Repeatability was similar in both planes and for both pairs of nurses. CONCLUSIONS: Nurses can achieve a high level of agreement in the measurement of aortic diameter in a routine clinical setting. PMID- 26902936 TI - Surgical Exposure to Control the Distal Internal Carotid Artery at the Base of the Skull during Carotid Aneurysm Repair. AB - Extracranial carotid artery aneurysms are rare. Treatment options for these lesions include endovascular interventions, such as coiling and stenting, or surgical reconstruction, such as resection and primary reanastomosis, or interposition bypass grafting. In this report, we describe the surgical technique used to perform surgical repair of an internal carotid artery aneurysm extending up to the base of the skull. Anterior exposure of the infratemporal fossa and distal control of the carotid artery at the level of the carotid canal was achieved through a transcervical approach, performing double mandibular osteotomies with superior reflection of the middle mandibular section. PMID- 26902937 TI - Type B Aortic Dissection with Abdominal Aortic Aneurysm Rupture 1 Year after Endovascular Repair of Abdominal Aortic Aneurysm. AB - We report a patient who developed a type B aortic dissection and ruptured his aneurysmal sac 1 year after endovascular abdominal aortic aneurysm repair (EVAR), despite standard follow-up. This 79-year-old man was presented to emergency room with acute abdominal pain and an acute lower limb ischemia. Computed tomography scan showed an acute type B aortic dissection feeding the aneurysmal sac of the EVAR. The aneurysm rupture occurred during imaging. Type B aortic dissection is a rare cause of aneurysmal rupture after EVAR. The first postoperative computed tomography scan should maybe include the arch and the descending thoracic aorta to rule out an iatrogenic dissection after EVAR. PMID- 26902938 TI - Radiation Exposure during Percutaneous Transluminal Angioplasty for Symptomatic Peripheral Arterial Disease. AB - BACKGROUND: Endovascular interventions often are the preferred treatment in peripheral arterial disease for both intermittent claudication and chronic critical limb ischemia. Ever more advanced and anatomically complex procedures are being performed, which may increase the radiation exposure of patients and medical staff. We sought to determine the radiation exposure sustained in contemporary interventional radiology practice. METHODS: A single-center observational cohort study of patients undergoing endovascular interventions for symptomatic peripheral arterial disease between January 1st, 2011 and July 31st, 2013 was performed. Radiation dose area product (DAP), peak skin dose (PSD), fluoroscopy time, and volume of contrast media were either measured or calculated and stratified according to patient demographics and anatomic location. RESULTS: In 951 patients, who were treated with endovascular interventions, mean DAP was 108 +/- 88 Gy * cm(2) and mean fluoroscopy time was 13 +/- 12 min. DAP was significantly higher for aortoiliac procedures (142 +/- 103 Gy * cm(2)) compared with femoral (58 +/- 73 Gy * cm(2)), below-knee (45 +/- 51 Gy * cm(2)) and multilevel (83 +/- 90 Gy * cm(2)) procedures (P < 0.001 for all comparisons). PSD was significantly higher for aortoiliac procedures (0.99 +/- 0.54 Gy) compared with femoral (0.55 +/- 0.55 Gy), below-knee (0.48 +/- 0.27 Gy), and multilevel (0.68 +/- 0.47 Gy) procedures (P < 0.001 for all comparisons). In contrast, mean fluoroscopy time in aortoiliac interventions was significantly shorter (10 +/- 15 min) compared with femoral (15 +/- 12 min), below-knee (19 +/- 10 min), and multilevel (23 +/- 14 min) procedures (P < 0.001 for all comparisons). CONCLUSIONS: Endovascular interventions in patients with symptomatic peripheral arterial disease involve a substantial radiation dose. Although fluoroscopy time is shorter, aortoiliac interventions result in greater radiation exposure than femoropopliteal or infrapopliteal interventions. PMID- 26902939 TI - Heparin-Induced Thrombocytopenia Associated with a Heparin-Bonded Stent Graft. AB - We describe a case of heparin-induced thrombocytopenia (HIT) in association with heparin-bonded stent grafts. A 61-year-old man with claudication secondary to a left superficial femoral artery (SFA) occlusion was treated with 2 heparin-bonded polytetrafluorethylene (hep-PTFE) grafts. Despite the use of antiplatelet medication, he presented with thrombosed hep-PTFE grafts 1 week after initial treatment. An additional hep-PTFE graft was placed at the SFA origin because of migration of the first graft. He was discharged on anticoagulation; however, he presented again 2 weeks later with recurrent SFA thrombosis and a platelet count of 60,000, raising suspicion for HIT. All exogenous forms of heparin were discontinued, and he was started on an alternative anticoagulant. The patient returned again 5 days after being discharged with recurrent symptoms of acute limb ischemia. He underwent a left femoropopliteal artery bypass with autogenous conduit and removal of the grafts. He has since had an uneventful recovery. We believe HIT should be considered as a potential cause of hep-PTFE graft thrombosis. Diagnosis and management of these patients is complex and may require explantation of the graft. PMID- 26902940 TI - Feasibility and Safety of Simultaneous Carotid Endarterectomy and Carotid Stenting for Bilateral Carotid Stenosis: A Single-Center Experience using a Hybrid Procedure. AB - BACKGROUND: The treatment for bilateral carotid stenosis (BCS) is challenging, and the optimal treatment strategy is not clear. We report our experience of treating 8 patients with BCS by simultaneous carotid endarterectomy (CEA) and carotid stenting (CAS), thereby providing an alternative for vascular surgeons. METHODS: Between October 2010 and August 2014, 8 patients (5 males and 3 females; range, 53-82 years; mean, 69 +/- 8.8 years) underwent simultaneous CEA and CAS in our hospital. CEA before CAS was done in 5 patients, and CAS before CEA was done in 3 patients. One patient also underwent simultaneous coronary artery bypass grafting due to unstable angina. Intraoperative transcranial Doppler ultrasonography, carotid shunts, patches, and embolic protection devices were used in all patients. Instances of hyperperfusion syndrome (HPS), hemodynamic depression, stroke, myocardial infarction (MI), and death were recorded. RESULTS: All patients completed the procedure. One patient developed postprocedural HPS. After systemic treatment, he recovered completely. There were no deaths, major and/or minor strokes, or MI, nor did any patient exhibit lower palsy in cranial nerves in the perioperative period (<30 days) or on clinical follow-up (3 and 6 months). We observed no restenosis and no recurrent symptoms during follow-up. CONCLUSIONS: After careful preoperative assessment and preparation, simultaneous CEA and CAS for high-grade BCS may be considered as an alternative management strategy in carefully selected patients. PMID- 26902942 TI - Effects of Endovascular Interventions on vWF and Fb Levels in Type 2 Diabetic Patients with Peripheral Artery Disease. AB - BACKGROUND: von Willebrand Factor (vWF) and fibrinogen (Fb) are associated with hypercoagulability and thrombosis, which are the pathology and symptom of arterial disease. This research aims to study the effects of endovascular interventions on blood vWF and Fb levels in patients with diabetic peripheral artery disease (PAD). METHODS: Totally, 66 type 2 diabetic patients with PAD (intervention group) and 26 type 2 diabetic patients without PAD (control group) were enrolled. These patients are matched at gender, age, and diabetes duration. For PAD patients, percutaneous interventions (balloon dilation or stent implantation) were performed, and blood samples were collected before, during, and after interventions. Then, enzyme-linked immunosorbent assay and prothrombin time-derived method were used to detect the levels of vWF and Fb, respectively. RESULTS: For intervention group, vWF and Fb levels in distal ischemic regions (vWF: 231.3%, Fb: 4.97 g/L) were significantly higher than that in nonischemic regions (vWF: 147.6%, Fb: 3.91 g/L, P value < 0.01). After interventions, ischemia was improved, whereas vWF and Fb levels were significantly increased (vWF: 299.2%, Fb: 5.69 g/L, P value < 0.01). During the 2 weeks after interventions, vWF and Fb levels reached a peak (vWF: 199.3%, Fb: 4.96 g/L) and then decreased gradually to lower than the preinterventional levels (vWF: 148.3%, Fb: 3.88 g/L, P value < 0.05). CONCLUSIONS: Interventions caused increases of blood vWF and Fb in the first week postintervention, leading to endothelial dysfunction and blood hypercoagulability. It suggested endothelial function protection and anticoagulant therapies should be applied to diabetic PAD patients after interventions. PMID- 26902941 TI - The Potential Effect of Epidural Anesthesia on Mesenteric Injury after Supraceliac Aortic Clamping in a Rabbit Model. AB - BACKGROUND: Epidural anesthesia is known to increase blood flow by producing vasodilatation on mesenteric circulation. In this experimental study, we aim to examine the effect of epidural anesthesia on mesenteric ischemic-reperfusion (IR) injury induced by supracoeliac aortic occlusion in a rabbit model. METHODS: Twenty-eight male white New Zealand rabbits were assigned into 4 separate groups, with 7 rabbits in each group: group I, control group; group II, IR-only group; group III, IR plus epidural anesthesia group; group IV, epidural anesthesia-only group. IR model was produced by clamping supraceliac aorta with an atraumatic vascular clamp for 60 min, followed by reperfusion for 120 min. An epidural catheter was placed via Th12-L1 intervertebral space by using open technique before aortic clamping in those assigned to epidural anesthesia. IR injury was assessed using blood markers interleukin-6 and IMA and tissue markers superoxide dismutase and malondialdehyde. Also histopathological examination was performed to evaluate the degree of injury. RESULTS: All biochemical markers in group II were significantly elevated in comparison with the other 3 groups (p < 0.05). This was paralleled by a more severe histopathological injury in IR- only group (group II). The group receiving IR plus epidural anesthesia (group III) had lower biochemical marker levels as compared with the IR-only group (group II). CONCLUSIONS: Mesenteric IR injury that can occur during abdominal aorta surgery can be reduced by epidural anesthesia, which is commonly used during or after major operations for pain control. Controlled clinical studies are required to evaluate these findings. PMID- 26902943 TI - Retrograde Proximal Anterior Tibial Artery Access for Treating Femoropopliteal Segment Occlusion: A Novel Approach. AB - Some challenges have been detected when there are long and complex lesions of femoropopliteal arterial occlusive disease, even with descriptions of the retrograde pedal approaches. The aim of this article is to describe the retrograde proximal anterior tibial artery access for treatment of femoropopliteal segment occlusion when antegrade recanalization failed (retrograde recanalization and rearranging the system into an antegrade position). Technical and clinical success was achieved in 100% of 4 cases, with an improvement of at least 2 Rutherford classes. Minor complication, small hematoma in an anterior compartment of the limb, occurred in 1 patient. No sign of compartmental syndrome was observed. PMID- 26902944 TI - Comparison of liquid exfoliated transition metal dichalcogenides reveals MoSe2 to be the most effective hydrogen evolution catalyst. AB - While 2D transition metal dichalcogenides are known to be promising materials for electrocatalysis of hydrogen production, it is not clear which member of this family of materials is the most effective catalyst. Here we perform a comprehensive study, comparing the catalytic performance of electrodes consisting of porous arrays of liquid exfoliated MX2 nanosheets (M = Mo, W; X = S, Se, Te). We find a clear hierarchy with selenides > sulphides > tellurides with MoSe2 clearly out-performing the other materials. In all cases the performance, as characterised by current density at a given potential, can be improved by increasing the number of active sites (via control of the electrode thickness) and/or by adding carbon nanotubes to the electrode (i.e. increasing the electrode conductivity). While all materials formed reasonably stable electrodes, addition of nanotubes tended to improve mechanical cohesion. In an attempt to maximise performance, we prepared thick (~15 MUm), free standing MoSe2/SWNT composite electrodes which displayed Tafel slopes of ~77 mV per decade and exchange current densities of ~0.1 mA cm(-2). These electrodes had low onset potentials, reaching 2 mA cm(-2) at -41 mV (vs. RHE) and generated high current densities of -35 mA cm(-2) at -200 mV (vs. RHE). PMID- 26902945 TI - Clinical Trial Watch: Reports from the Liver Meeting(r), AASLD, San Francisco, November 2015. PMID- 26902946 TI - The Influence of Social Determinants on Late Stage Breast Cancer for Women in Mississippi. AB - INTRODUCTION: Breast cancer is the most common diagnosed cancer in women exacting an emotional and economic hardship for them and their families. There are no known causes of breast cancer, but there are certain genetic, social, and environment risk factors that pre-dispose women to this disease. Also, diagnosis at later stages of disease has been shown to have adverse outcomes for many as compared to early stages. The social determinants researched to examine their influence on breast cancer outcomes were race, health insurance, and income. The results of this study confirmed that race and health insurance were the two major factors that negatively impacted stages of breast cancer diagnoses. PURPOSE: The purpose of this study was to investigate the influence that social determinants have on stage of breast cancer diagnoses. This research focused on three social determinants that research demonstrated had an influence on stages of breast cancer diagnoses (race, income, and lack of health insurance). METHODS: Bivariate analyses were conducted to examine the relationships between race and income, race and health insurance, and race and stage of diagnosis. The findings confirmed what was suspected for Mississippians; more African Americans had lower incomes, had less health insurance coverage, and were diagnosed at later stages of breast cancer disease. RESULTS: Only race and health insurance directly affected late stage diagnosis in analyses for this study. The influence of income on stage of breast cancer diagnosis was not statistically significant. The results of these analyses demonstrated that African American women in Mississippi were disproportionately diagnosed at late stage breast cancer as opposed to early stage. CONCLUSIONS: An individual cannot alter the genetic factor of race, but some of the disparate health outcomes that appear to be associated with race may be behavioral or socio-economically based and can be addressed, which could impact health outcomes. Adequate health insurance could positively impact stage of breast cancer diagnoses, ultimately reducing health disparities and premature death. PMID- 26902948 TI - Charging and aggregation of latex particles in aqueous solutions of ionic liquids: towards an extended Hofmeister series. AB - The effect of ionic liquid (IL) constituents and other monovalent salts on the stability of polystyrene latex particles was studied by electrophoresis and light scattering in dilute aqueous suspensions. The surface charge and the aggregation rate were both sensitive to the type of ion leading to different critical coagulation concentration (CCC) values. Systematic variation of the type of IL cation and anion allows us to place these ions within the Hofmeister series. We find that the dicyanoamide anion should be placed between iodide and thiocyanate, while all 1-alkyl-3-methylimidazolium cations can be positioned to the left of the tetramethylammonium and ammonium ions. The hydrophobicity of the 1-butyl-1 methylpyrrolidinium (BMPL(+)) ion is intermediate between 1-ethyl-3 methylimidazolium (EMIM(+)) and 1-butyl-3-methylimidazolium (BMIM(+)). With increasing alkyl chain length, the 1-alkyl-3-methylimidazolium cations adsorb on the latex particles very strongly, and 1-hexyl-3-methylimidazolium (HMIM(+)) and 1-octyl-3-methylimidazolium (OMIM(+)) lead to pronounced charge reversal and to an intermediate restabilization region. PMID- 26902947 TI - Probing Protein 3D Structures and Conformational Changes Using Electrochemistry Assisted Isotope Labeling Cross-Linking Mass Spectrometry. AB - This study presents a new chemical cross-linking mass spectrometry (MS) method in combination with electrochemistry and isotope labeling strategy for probing both protein three-dimensional (3D) structures and conformational changes. For the former purpose, the target protein/protein complex is cross-linked with equal mole of premixed light and heavy isotope labeled cross-linkers carrying electrochemically reducible disulfide bonds (i.e., DSP-d0 and DSP-d8 in this study, DSP = dithiobis[succinimidyl propionate]), digested and then electrochemically reduced followed with online MS analysis. Cross-links can be quickly identified because of their reduced intensities upon electrolysis and the presence of doublet isotopic peak characteristics. In addition, electroreduction converts cross-links into linear peptides, facilitating MS/MS analysis to gain increased information about their sequences and modification sites. For the latter purpose of probing protein conformational changes, an altered procedure is adopted, in which the protein in two different conformations is cross-linked using DSP-d0 and DSP-d8 separately, and then the two protein samples are mixed in 1:1 molar ratio. The merged sample is subjected to digestion and electrochemical mass spectrometric analysis. In such a comparative cross-linking experiment, cross-links could still be rapidly recognized based on their responses to electrolysis. More importantly, the ion intensity ratios of light and heavy isotope labeled cross-links reveal the conformational changes of the protein, as exemplified by examining the effect of Ca(2+) on calmodulin conformation alternation. This new cross-linking MS method is fast and would have high value in structural biology. Graphical Abstract ?. PMID- 26902949 TI - The Expression of the Suicide-Associated Gene SKA2 Is Decreased in the Prefrontal Cortex of Suicide Victims but Not of Nonsuicidal Patients. AB - BACKGROUND: Recent study of genome-wide DNA methylation profiling in the postmortem brain of suicidal and nonsuicidal subjects found that gene expression of spindle and kinetochore associated complex subunit 2 (SKA2) is decreased in the postmortem brain of suicide victims compared with nonsuicidal, nonpsychiatric control subjects. METHODS: To determine if decreased SKA2 is specific to suicide and independent of diagnosis, we determined gene and protein expression of SKA2 in the prefrontal cortex obtained from suicide victims (n= 52), nonsuicidal psychiatric subjects (n= 27), and normal controls (n= 24). We determined gene expression by quantitative PCR technique and protein expression by Western blot. The postmortem brain samples were obtained from the Maryland Psychiatric Research Center. RESULTS: We found that protein and gene expression of SKA2 was significantly reduced in the prefrontal cortex of suicide victims compared with normal control subjects and nonsuicidal patients. We also found that SKA2 protein and gene expression in depressed suicide victims, schizophrenic suicide victims, and suicide victims with substance abuse and/or conduct disorders was significantly decreased compared with normal control subjects and also with nonsuicidal depressed or schizophrenic subjects. CONCLUSIONS: This study shows that decreased gene and protein expression of SKA2 observed in the prefrontal cortex of suicide victims is specific to suicide, which was not observed in the brain of nonsuicidal patients. It also indicates reduced SKA2 expression in suicide is independent of psychiatric diagnosis, since it is observed in all diagnostic groups studied. Therefore, SKA2 may be a potential biomarker for suicide. PMID- 26902950 TI - Efficacy and Safety of Paliperidone Palmitate 3-Month Formulation for Patients with Schizophrenia: A Randomized, Multicenter, Double-Blind, Noninferiority Study. AB - BACKGROUND: This double-blind, parallel-group, multicenter, phase-3 study was designed to test the noninferiority of paliperidone palmitate 3-month formulation (PP3M) to the currently marketed 1-month formulation (PP1M) in patients (age 18 70 years) with schizophrenia, previously stabilized on PP1M. METHODS: After screening (<=3 weeks) and a 17-week, flexible-dosed, open-label phase (PP1M: day 1 [150mg eq. deltoid], day 8 [100mg eq. deltoid.], weeks 5, 9, and 13 [50, 75, 100, or 150mg eq., deltoid/gluteal]), clinically stable patients were randomized (1:1) to PP3M (fixed-dose, 175, 263, 350, or 525mg eq. deltoid/gluteal) or PP1M (fixed-dose, 50, 75, 100, or 150mg eq. deltoid/gluteal) for a 48-week double blind phase. RESULTS: Overall, 1016/1429 open-label patients entered the double blind phase (PP3M: n=504; PP1M: n=512) and 842 completed it (including patients with relapse). PP3M was noninferior to PP1M: relapse rates were similar in both groups (PP3M: n=37, 8%; PP1M: n=45, 9%; difference in relapse-free rate: 1.2% [95% CI:-2.7%; 5.1%]) based on Kaplan-Meier estimates (primary efficacy). Secondary endpoint results (changes from double-blind baseline in positive and negative symptom score total and subscale scores, Clinical Global Impression Severity, and Personal and Social Performance scores) were consistent with primary endpoint results. No clinically relevant differences were observed in pharmacokinetic exposures between PP3M and PP1M. Both groups had similar tolerability profiles; increased weight was the most common treatment-emergent adverse event (double-blind phase; 21% each). No new safety signals were detected. CONCLUSION: Taken together, PP3M with its 3-month dosing interval is a unique option for relapse prevention in schizophrenia. PMID- 26902952 TI - Tight-binding calculation studies of vacancy and adatom defects in graphene. AB - Computational studies of complex defects in graphene usually need to deal with a larger number of atoms than the current first-principles methods can handle. Here, we show that a recently developed three-center tight-binding potential for carbon is very efficient for large scale atomistic simulations and can accurately describe the structures and energies of various defects in graphene. Using the three-center tight-binding potential, we have systematically studied the stable structures and formation energies of vacancy and embedded-atom defects of various sizes up to four vacancies and four embedded atoms in graphene. Our calculations reveal low-energy defect structures and provide a more comprehensive understanding of the structures and stability of defects in graphene. PMID- 26902951 TI - A novel monolithic controlled delivery system of resveratrol for enhanced hepatoprotection: nanoformulation development, pharmacokinetics and pharmacodynamics. AB - The current investigation aims to present a novel solid lipid-based nanoparticulate system of resveratrol (RV) for the effective treatment of liver cirrhosis. A simplified solvent injection method was employed and the Box-Behnken experimental design was applied for optimization to get a window particle size of 150-200 nm having maximum entrapment efficiency as well as % release. Optimized resveratrol solid lipid nanoparticles (RV-SLNs) (SR-1) of appropriate characteristics (particle size = 191.1 +/- 10.44 nm; zeta potential= -13.56 +/- 4.14 mV; entrapment efficiency = 75.23 +/- 3.85%; maximum % release = 80.53 +/- 3.99%) were produced. Differential scanning calorimetry and X-ray diffraction studies were carried out which collectively proved the reduced crystallinity and stability enhancing the effect of the SLNs. Improved drug stability was further established by the appreciable shelf-life of the formulation from International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH)-recommended accelerated stability studies. In vivo studies revealed nearly five-fold increase in the bioavailability of SR-1 (AUC0->infinity=3411 +/- 170.34 ug/ml/h) as compared to RV suspension (AUC0->infinity=653.5 +/- 30.10 ug/ml/h). Pharmacodynamic data exhibited a significant decrease in the serum biomarker enzymes (serum glutamic oxalo-acetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) and alkaline phosphatase) after oral administration of RV-SLNs as compared to control and marketed (SILYBON((r))) formulations against paracetamol-induced liver cirrhosis. The effect of the treatment was confirmed by the histopathology of the liver microtome sections. Finally, reverse transcriptase-polymerase chain reaction studies were conducted on isolated liver mRNA from SR-1 treated animals and significant down-regulation of tissue inhibitor of metalloproteinases-1 and nuclear factor-kB was witnessed. PMID- 26902953 TI - Superior electric storage on an amorphous perfluorinated polymer surface. AB - Amorphous perfluoroalkenyl vinyl ether polymer devices can store a remarkably powerful electric charge because their surface contains nanometre-sized cavities that are sensitive to the so-called quantum-size effect. With a work function of approximately 10 eV, the devices show a near-vertical line in the Nyquist diagram and a horizontal line near the -90 degrees phase angle in the Bode diagram. Moreover, they have an integrated effect on the surface area for constant current discharging. This effect can be explained by the distributed constant electric circuit with a parallel assembly of nanometre-sized capacitors on a highly insulating polymer. The device can illuminate a red LED light for 3 ms after charging it with 1 mA at 10 V. Further gains might be attained by integrating polymer sheets with a micro-electro mechanical system. PMID- 26902954 TI - A new safe and cost-effective percutaneous dilatational tracheotomy: SafeTrach. AB - Conclusion SafeTrach is a new simplified and safe technique to perform percutaneous dilatational tracheotomy (PDT) that eliminates known risk factors compared with existing percutaneous techniques. In the present clinical study, also patients with disadvantageous anatomy not suitable for conventional PDT (CPDT) were treated without complications using SafeTrach. PDT with SafeTrach (STPDT) offers an excellent solution for patients who need tracheotomy in connection with elective ear, nose, and throat (ENT) surgery. Objectives To assess a new technique for percutaneous tracheotomy. Methods Seventeen patients were tracheotomized with STPDT using SafeTrach for the initial penetration sequence and single step dilatational techniques for the dilatational sequence. The patients represented a variety of different neck anatomies. Fifteen patients were head- and neck cancer patients that were subjects of free flap transplants. Results This study showed that STPDT was safe and easy to perform and time efficient. The median duration of the procedure was 11.5 min and the puncture was in all cases located in the midline of the trachea either between the 2nd and 3rd tracheal ring (n = 13) or between the 3rd and 4th ring (n = 4). PMID- 26902955 TI - Van der Waals stacks of few-layer h-AlN with graphene: an ab initio study of structural, interaction and electronic properties. AB - Graphite-like hexagonal AlN (h-AlN) multilayers have been experimentally manifested and theoretically modeled. The development of any functional electronics applications of h-AlN would most certainly require its integration with other layered materials, particularly graphene. Here, by employing vdW corrected density functional theory calculations, we investigate structure, interaction energy, and electronic properties of van der Waals stacking sequences of few-layer h-AlN with graphene. We find that the presence of a template such as graphene induces enough interlayer charge separation in h-AlN, favoring a graphite-like stacking formation. We also find that the interface dipole, calculated per unit cell of the stacks, tends to increase with the number of stacked layers of h-AlN and graphene. PMID- 26902956 TI - An economic analysis of pancreaticoduodenectomy: should costs drive consumer decisions? AB - BACKGROUND: Consumer groups campaign for cost transparency believing that patients will select hospitals accordingly. We sought to determine whether the cost of pancreaticoduodenectomy (PD) should be considered in choosing a hospital. METHODS: Using the Nationwide Inpatient Sample database, we analyzed charges for patients who underwent PD from 2000 to 2010. Outcomes were stratified by hospital volume. RESULTS: A total of 15,599 PDs were performed in 1,186 hospitals. The median cost was $87,444 (interquartile range $16,015 to $144,869). High volume hospitals (HVH) had shorter hospital stay (11 vs 15 days, P < .001) and mortality (3% vs 7.6%, P < .001). PD performed at low volume hospitals had higher charges compared with HVH ($97,923 vs $81,581, P < .001). On multivariate analysis, HVH was associated with a lower risk of mortality, while extremes in hospital costs, cardiac comorbidity, and any complication were significant predictors of mortality. CONCLUSION: Although PDs performed at HVH are associated with better outcomes and lower hospital charges, costs should not be the primary determinant when selecting a hospital. PMID- 26902957 TI - Omental adhesion, intestinal herniation, and unexpected death in the elderly. PMID- 26902959 TI - The Role of Pediatricians in the Face of Increasing Domestic Terrorism Threats. PMID- 26902958 TI - Prevalence of and risk factors for feline hyperthyroidism among a clinic population in Southern Germany. AB - OBJECTIVES: Feline hyperthyroidism is a common endocrine disorder in older cats. Previous studies have identified nutritional imbalances, thyroid-disrupting compounds, increasing age and being non-purebred as risk factors but the final trigger remains unknown. The purpose of this prospective study was a) to determine the hospital prevalence of hyperthyroidism in a client-owned cat population in Southern Germany, b) to exploit how frequently hyperthyroidism was diagnosed after the initial clinical suspicion and c) to determine putative intrinsic and extrinsic risk factors from the cats' signalment and a questionnaire analysis, respectively. METHODS: Total thyroxine (T4) was measured in sera of 495 cats >= 8 years. Prevalence was calculated with a 95% confidence interval (95% CI) Association between signalment and hyperthyroidism was analysed by Student's unpaired-t-test, chi-square test and Mann-Whitney U-test. Level of significance was set at 0.05. Multivariate logistic regression model was used to determine extrinsic risk factors. RESULTS: Sixty-one cats were diagnosed with hyperthyroidism leading to a prevalence of 12.3% (95% CI: 9.7-15.5). Older (p < 0.001) female cats (p = 0.019; odds ratio 1.9) were significantly more often affected. Domestic shorthair and domestic longhair cats were more likely hyperthyroid than purebred cats (p = 0.016). In 164 cats hyperthyroidism was considered a differential diagnosis and was verified in 20.1% (33/164). In 2.4% (12/495) cases the elevated T4 was an incidental finding. Hyperthyroid cats were more likely to be fed with moist cat food from aluminum tins (p < 0.013) compared to non-hyperthyroid cats. CONCLUSION AND CLINICAL RELEVANCE: Older, female non purebred cats are predisposed to hyperthyroidism which is frequently diagnosed after the initial clinical suspicion leading to a prevalence of 12.3% among the study population. Components of the aluminum tins or the moist food itself or both may play a role in the etiopathogenesis. PMID- 26902960 TI - Is plant evolutionary history impacting recruitment of diazotrophs and nifH expression in the rhizosphere? AB - Plant evolutionary history influences the taxonomic composition of the root associated bacterial community, but whether it can also modulate its functioning is unknown. Here, we tested the hypothesis that crop diversification is a significant factor determining the ecology of the functional group of nitrogen fixing bacteria the rhizosphere of Poaceae. A greenhouse experiment was carried out using a range of Poaceae, i.e. four Zea mays varieties (from two genetic groups) and teosinte (representing maize's ancestor), sorghum (from the same Panicoideae subfamily), and wheat (from neighboring Pooideae subfamily), as well as the dicot tomato as external reference. Diazotroph rhizosphere community was characterized at 21 days in terms of size (quantitative PCR of nifH genes), composition (T-RFLP and partial sequencing of nifH alleles) and functioning (quantitative RT-PCR, T-RFLP and partial sequencing of nifH transcripts). Plant species and varieties had a significant effect on diazotroph community size and the number of nifH transcripts per root system. Contrarily to expectations, however, there was no relation between Poaceae evolutionary history and the size, diversity or expression of the rhizosphere diazotroph community. These results suggest a constant selection of this functional group through evolution for optimization of nitrogen fixation in the rhizosphere. PMID- 26902965 TI - Alcoholic liver disease and transplantation: the necessity for hepato alcohologists. PMID- 26902963 TI - Clinical trials: New drug for pancreatic cancer highlights the dual effect of regulatory approvals. PMID- 26902966 TI - Genetic variants in ultraconserved regions associate with prostate cancer recurrence and survival. AB - Ultraconserved regions (UCRs) are DNA segments of longer than 200 bp in length that are completely conserved between human, rat, and mouse genomes. Recent studies have shown that UCRs are frequently located at fragile sites involved in cancers, and their levels of transcription can be altered during human tumorigenesis. We systematically evaluated 14 common single-nucleotide polymorphisms (SNPs) within UCRs in three cohorts of prostate cancer patients, to test the hypothesis that these UCR SNPs might influence clinical outcomes. Examination using multivariate analysis adjusted for known clinicopathologic factors found association between rs8004379 and recurrence in localized disease [hazard ratio (HR) 0.61, 95% confidence interval (CI) 0.41-0.91, P = 0.015], which was confirmed in the replication set (HR 0.70, 95% CI 0.51-0.96, P = 0.027). Remarkably, a consistent association of rs8004379 with a decreased risk for prostate cancer-specific mortality was also observed in the advanced prostate cancer patient group (HR 0.48, 95% CI 0.32-0.70, P < 0.001). Additional in silico analysis suggests that rs8004379 tends to affect NPAS3 expression, which in turn was found to be correlated with patient prognosis. In conclusion, our findings suggest that SNPs within UCRs may be valuable prognostic biomarkers for assessing prostate cancer treatment response and survival. PMID- 26902969 TI - From Flexible and Stretchable Meta-Atom to Metamaterial: A Wearable Microwave Meta-Skin with Tunable Frequency Selective and Cloaking Effects. AB - This paper reports a flexible and stretchable metamaterial-based "skin" or meta skin with tunable frequency selective and cloaking effects in microwave frequency regime. The meta-skin is composed of an array of liquid metallic split ring resonators (SRRs) embedded in a stretchable elastomer. When stretched, the meta skin performs as a tunable frequency selective surface with a wide resonance frequency tuning range. When wrapped around a curved dielectric material, the meta-skin functions as a flexible "cloaking" surface to significantly suppress scattering from the surface of the dielectric material along different directions. We studied frequency responses of multilayer meta-skins to stretching in a planar direction and to changing the spacing between neighboring layers in vertical direction. We also investigated scattering suppression effect of the meta-skin coated on a finite-length dielectric rod in free space. This meta-skin technology will benefit many electromagnetic applications, such as frequency tuning, shielding, and scattering suppression. PMID- 26902970 TI - Fracture patterns and the energy release rate of phosphorene. AB - Phosphorene, also known as monolayer black phosphorus, has been enjoying popularity in electronic devices due to its superior electrical properties. However, it's relatively low Young's modulus, low fracture strength and susceptibility to structural failure have limited its application in mechanical devices. Therefore, in order to design more mechanically reliable devices that utilize phosphorene, it is necessary to explore the fracture patterns and energy release rate of phosphorene. In this study, molecular dynamics simulations are performed to investigate phosphorene's fracture mechanism. The results indicate that fracture under uniaxial tension along the armchair direction is attributed to a break in the interlayer bond angles, while failure in the zigzag direction is triggered by the break in both intra-layer angles and bonds. Furthermore, we developed a modified Griffith criterion to analyze the energy release rate of phosphorene and its dependence on the strain rates and orientations of cracks. Simulation results indicate that phosphorene's energy release rate remains almost unchanged in the armchair direction while it fluctuates intensively in the zigzag direction. Additionally, the strain rate was found to play a negligible role in the energy release rate. The geometrical factor alpha in the Griffith's criterion is almost constant when the crack orientation is smaller than 45 degree, regardless of the crack orientation and loading direction. Overall, these findings provide helpful insights into the mechanical properties and failure behavior of phosphorene. PMID- 26902968 TI - Oxidative stress decreases microtubule growth and stability in ventricular myocytes. AB - Microtubules (MTs) have many roles in ventricular myocytes, including structural stability, morphological integrity, and protein trafficking. However, despite their functional importance, dynamic MTs had never been visualized in living adult myocytes. Using adeno-associated viral vectors expressing the MT-associated protein plus end binding protein 3 (EB3) tagged with EGFP, we were able to perform live imaging and thus capture and quantify MT dynamics in ventricular myocytes in real time under physiological conditions. Super-resolution nanoscopy revealed that EB1 associated in puncta along the length of MTs in ventricular myocytes. The vast (~80%) majority of MTs grew perpendicular to T-tubules at a rate of 0.06MUm*s(-1) and growth was preferentially (82%) confined to a single sarcomere. Microtubule catastrophe rate was lower near the Z-line than M-line. Hydrogen peroxide increased the rate of catastrophe of MTs ~7-fold, suggesting that oxidative stress destabilizes these structures in ventricular myocytes. We also quantified MT dynamics after myocardial infarction (MI), a pathological condition associated with increased production of reactive oxygen species (ROS). Our data indicate that the catastrophe rate of MTs increases following MI. This contributed to decreased transient outward K(+) currents by decreasing the surface expression of Kv4.2 and Kv4.3 channels after MI. On the basis of these data, we conclude that, under physiological conditions, MT growth is directionally biased and that increased ROS production during MI disrupts MT dynamics, decreasing K(+) channel trafficking. PMID- 26902971 TI - News and Internet Searches About Human Immunodeficiency Virus After Charlie Sheen's Disclosure. PMID- 26902973 TI - Synthesis of Alkaloid-Mimicking Tricyclic Skeletons by Diastereo- and Regioselective Ugi/ipso-Cyclization/Aza-Michael Cascade Reaction in One-Pot. AB - A one-pot process has been developed for preparing alkaloid-like tricyclic skeletons by employing an Ugi reaction, an acid mediated ipso-cyclization and an aza-Michael addition. The transformation is operationally simple and provides products in a diastereo- and regioselective manner with good-to-excellent yields. PMID- 26902972 TI - Pulse pressure as an independent predictor of stroke: a systematic review and a meta-analysis. AB - BACKGROUND: Recent evidence suggests that pulse pressure (PP) is a strong cardiovascular diseases' risk factor. We systematically evaluated all relevant studies to determine whether PP can be used as an independent predictor of stroke and mortality. METHODS AND RESULTS: A meta-analysis was performed by searching the published literature using MEDLINE, Cochrane and Google Scholar databases up to December 15, 2015. We measured the effect size expressed by hazard ratio (HR) and 95 % confidence interval (95 % CI). Eleven publications were included in the analysis. Pooled results demonstrated that 10 mmHg increase in PP was associated with increased risk of stroke occurrence (pooled HR 1.046, 95 % CI 1.025-1.068, P < 0.001). Additionally, systolic blood pressure (SBP) (pooled HR 1.053, 95 % CI 1.033-1.073, P < 0.001) and diastolic blood pressure (DPB) (pooled HR 1.056, 95 % CI 1.038-1.074, P < 0.001) were found to be significant predictors for stroke. We did not find a significant association between PP and all-cause mortality (pooled HR 1.022, 95 % CI 0.983-1.063, P = 0.270). We found SBP (pooled HR 1.008, 95 % CI 1.002-1.014, P = 0.012), but not DBP (pooled HR 1.023, 95 % CI 0.964-1.085, P = 0.451) to be significantly associated with all-cause mortality. CONCLUSIONS: Current data confirms that PP is an independent risk factor for stroke but is not a predictor of mortality. PMID- 26902974 TI - Inverted Ultrathin Organic Solar Cells with a Quasi-Grating Structure for Efficient Carrier Collection and Dip-less Visible Optical Absorption. AB - We propose a metallic-particle-based two-dimensional quasi-grating structure for application to an organic solar cell. With the use of oblate spheroidal nanoparticles in contact with an anode of inverted, ultrathin organic solar cells (OSCs), the quasi-grating structure offers strong hybridization between localized surface plasmons and plasmonic gap modes leading to broadband (300~800 nm) and uniform (average ~90%) optical absorption spectra. Both strong optical enhancement in extreme confinement within the active layer (90 nm) and improved hole collection are thus realized. A coupled optical-electrical multi-physics optimization shows a large (~33%) enhancement in the optical absorption (corresponding to an absorption efficiency of ~47%, AM1.5G weighted, visible) when compared to a control OSC without the quasi-grating structure. That translates into a significant electrical performance gain of ~22% in short circuit current and ~15% in the power conversion efficiency (PCE), leading to an energy conversion efficiency (~6%) which is comparable to that of optically-thick inverted OSCs (3-7%). Detailed analysis on the influences of mode hybridization to optical field distributions, exciton generation rate, charge carrier collection efficiency and electrical conversion efficiency is provided, to offer an integrated understanding on the coupled optical-electrical optimization of ultrathin OSCs. PMID- 26902975 TI - Comparison of retinal vessel measurements using adaptive optics scanning laser ophthalmoscopy and optical coherence tomography. AB - PURPOSE: We compared adaptive optics scanning laser ophthalmoscopy (AOSLO) and optical coherence tomography (OCT) vessel caliber measurements. METHODS: AOSLO videos were acquired from 28 volunteers with healthy eyes. Artery measurements were made 0.5-1 disc diameters away from the optic disc margin. Individual segmented retinal arterial caliber was measured in synchronization with cardiac pulsation and averaged to obtain final horizontal retinal arterial caliber (ACH) and horizontal retinal arterial lumen (ALH). All OCT images were obtained with the Spectralis OCT, a spectral-domain OCT system. Vertical retinal arterial caliber (ACV) and vertical retinal arterial lumen (ALV) were measured on the same artery measured with AOSLO. Measurements made with the two imaging systems were compared. RESULTS: Average ACH, measured with AOSLO, was 123.4 +/- 11.2 and average ALH was 101.8 +/- 10.2 um. Average ACV, measured with OCT, was 125.5 +/- 11.4 and average ALV was 99.1 +/- 10.6 um. Both arterial caliber (r = 0.767, p < 0.0001) and arterial lumen (r = 0.81, p < 0.0001) measurements were significantly correlated between imaging modalities. Additionally, ACH and ACV were not significantly different (p = 0.16). However, ALH measurements were significantly higher than ALV measurements (p = 0.03). CONCLUSIONS: Vessel measurements made with AOSLO and OCT were well correlated. Moreover, plasma is visible and distinguishable from the retinal vessel wall in AOSLO images but not in OCT images. Therefore, AOSLO may measure vessel width more precisely than OCT. PMID- 26902976 TI - Monocular retinal degeneration induced by intravitreal injection of sodium iodate in rabbit eyes. AB - PURPOSE: Our purpose was to evaluate the anatomical and functional changes in retinae of rabbit eyes following monocular intravitreal injection of sodium iodate (SI). METHODS: Twenty albino rabbits were divided into four groups and underwent monocular intravitreal injection with four different doses of SI (0.1, 0.2, 0.4, and 0.8 mg). Before and for 28 days after injection, the eyes were examined using fundus photography, optical coherence tomography (OCT), and electroretinography (ERG). At postinjection days 2, 7, and 28, the eyes were enucleated and underwent histological examination. RESULTS: On fundus examination, no distinct retinal changes were seen in any group except the 0.8-mg group, which showed chorioretinal vascular attenuation. In 0.1 and 0.2-mg groups, no significant anatomical changes were found except transient hyperreflective dots over the vitreoretinal interface on OCT. In 0.4 and 0.8-mg groups, disruption of the ellipsoid zone and diffuse retinal swelling were observed in the early period on OCT. In the 0.4-mg group, the outer retina was significantly destroyed at day 28, whereas the inner retina was relatively preserved. In the 0.8-mg group, the entire retina was destroyed irreversibly. The b-wave of ERG was reduced immediately in all groups, which recovered fully (0.1- and 0.2-mg groups), partially (0.4-mg group), or never (0.8-mg group). No structural or functional abnormalities were found in the fellow control eyes. CONCLUSIONS: Retinal degeneration following intravitreal injection of SI appears to be dose dependent; retinal damage is reversible at low doses but irreversible at high doses. At a certain dose, the outer retina may be preferably ablated. PMID- 26902978 TI - Evaluation of Parotid Lesions. AB - The differential diagnosis of a parotid lesion is broad, and the otolaryngologist must consider inflammatory, neoplastic, autoimmune, traumatic, infectious, or congenital causes. A comprehensive history and physical examination, in conjunction with judicious use of radiographic imaging (MRI, computed tomography, ultrasonography, nuclear medicine studies), laboratory studies, and pathologic analysis (fine-needle aspiration, core biopsy, incisional biopsy), facilitates making an accurate diagnosis. This article reviews the key history and physical elements and adjunctive diagnostic tools available for working up parotid lesions. PMID- 26902977 TI - Low serum vitamin D occurs commonly among multiple myeloma patients treated with bortezomib and/or thalidomide and is associated with severe neuropathy. AB - PURPOSE: Previous studies have shown that low serum vitamin D levels have been associated with many skeletal and non-skeletal disorders. We studied the relationship between 25-hydroxyvitamin D (25D) levels and motor and sensory peripheral neuropathy (PN) among multiple myeloma (MM) patients who have been treated with bortezomib and/or thalidomide. METHODS: We performed a study of 111 MM patients who had received at least one of these two agents for at least 12 weeks by correlating physical exam/neurologic assessment findings with patient self-assessment responses. RESULTS: The median age of study patients was 66 years (range 42-89 years) and 54 % were males. 25D levels were determined, and complete history and physical and neurologic examinations were performed at the same study visit. In addition, study subjects completed questionnaires regarding symptoms related to motor and sensory PN. Overall, patients had a median serum 25D level of only 32 ng/ml; 42 % of patients were considered either 25D-deficient (<20.0 ng/mL; 16 % of patients) or 25D-insufficient (20.0-29.9 ng/mL; 26 %). Notably, we found that 25D-deficient MM patients were more likely to have severe PN (>grade 2) of both motor (p = 0.0415) and sensory (p = 0.0086) types although the overall incidence of PN was not higher in this patient population. CONCLUSION: These results show that the severity of peripheral neuropathy is associated with lower vitamin D levels and provides the rationale for monitoring vitamin D for myeloma patients especially those receiving drugs associated with the development of peripheral neuropathy. PMID- 26902979 TI - Facial Paralysis Reconstruction. AB - Facial nerve paralysis is a devastating condition arising from several causes with severe functional and psychological consequences. Given the complexity of the disease process, management involves a multispecialty, team-oriented approach. This article provides a systematic approach in addressing each specific sequela of this complex problem. PMID- 26902980 TI - Parotid Gland Imaging. AB - In this article, various imaging modalities are discussed for evaluation of parotid disease, from congenital to inflammatory to neoplastic etiologies. Key imaging characteristics are outlined using case examples. Introduction to biological imaging is highlighted. Additionally, image-guided biopsy techniques are illustrated for sampling parotid and parapharyngeal space lesions in a minimally invasive manner. PMID- 26902981 TI - Rare Parotid Gland Diseases. AB - The differential diagnosis for "rare" parotid gland diseases is broad and encompasses infectious, neoplastic, autoimmune, metabolic, and iatrogenic etiologies. The body of knowledge of parotid gland diseases has grown owing to advances in imaging and pathologic analysis and molecular technology. This article reviews rare parotid diseases, discussing the respective disease's clinical presentation, diagnosis, imaging, pathogenesis, treatment, and prognosis. PMID- 26902982 TI - Auriculotemporal Syndrome (Frey Syndrome). AB - Frey syndrome is a common sequela of parotidectomy, and although it is not frequently manifested clinically, it can cause significant morbidity for those affected. Frey syndrome results from synkinetic autonomic reinnervation by transected postganglionic parasympathetic nerve fiber within the parotid gland to the overlying sweat glands of the skin. Many surgical techniques have been proposed to prevent the development of Frey syndrome. For those who develop clinical symptoms of Frey syndrome, objective testing can be performed with a Minor starch-iodine test. Some of the current methods to prevent and treat symptomatic Frey syndrome are reviewed. PMID- 26902984 TI - A new robotic assistance system for percutaneous CT-guided punctures: Initial experience. AB - PURPOSE: To evaluate the feasibility of CT-guided bone biopsies using a novel robotic needle guide. MATERIAL AND METHODS: The robotic needle guide iSYS 1.3 (iSYS Medzintechnik, GmbH, Kitzbuehel, Austria) mounted on the standard table of a CT scanner was used for all studies. For preclinical testing, eight vertebral bodies of dead swine were biopsied, trying to place the needle in the center of the vertebral body via a transpedicular access. For clinical evaluation, bone biopsies were taken in three different patients with ambiguous bone lesions. All biopsies were performed under general anesthesia, using a 12G bone biopsy needle. RESULTS: The animal studies demonstrated that the biopsy needle could be placed accurately in the center of the vertebral body in all cases. No readjustment was necessary, the CT scans demonstrated an intrapedicular trajectory avoiding the spinal canal or the neural foramina. Subsequently, following the animal studies, all biopsies could be performed successfully. Needle placement was accurate without any need for readjustment. No complications occurred during the procedure. CONCLUSION: Using the iSYS 1.3 allows for accurate and simple stereotactic biopsies of bone lesions, avoiding the need for needle readjustment. The systems may offer even less experienced teams to take biopsies in regions which are difficult to access. PMID- 26902983 TI - Maternal physiological dysregulation while parenting poses risk for infant attachment disorganization and behavior problems. AB - The extent to which indices of maternal physiological arousal (skin conductance augmentation) and regulation (vagal withdrawal) while parenting predict infant attachment disorganization and behavior problems directly or indirectly via maternal sensitivity was examined in a sample of 259 mothers and their infants. Two covariates, maternal self-reported emotional risk and Adult Attachment Interview attachment coherence were assessed prenatally. Mothers' physiological arousal and regulation were measured during parenting tasks when infants were 6 months old. Maternal sensitivity was observed during distress-eliciting tasks when infants were 6 and 14 months old, and an average sensitivity score was calculated. Attachment disorganization was observed during the Strange Situation when infants were 14 months old, and mothers reported on infants' behavior problems when infants were 27 months old. Over and above covariates, mothers' arousal and regulation while parenting interacted to predict infant attachment disorganization and behavior problems such that maternal arousal was associated with higher attachment disorganization and behavior problems when maternal regulation was low but not when maternal regulation was high. This effect was direct and not explained by maternal sensitivity. The results suggest that maternal physiological dysregulation while parenting places infants at risk for psychopathology. PMID- 26902985 TI - Safe endobag morcellation in a single-port laparoscopy subtotal hysterectomy. AB - Recently, the American Food and Drug Administration (FDA) published an alert about the risks of uterine tissue morcellation during laparoscopic procedures. In particular, the possible risk of spreading an undiagnosed malignant tumor was emphasized. From then on, a fervent debate in the media has led major scientific societies to express their position on the matter. We present a safe endobag abdominal morcellation in a single port-access laparoscopy subtotal hysterectomy. The endobag abdominal morcellation is feasible and safe; consequently, the development of devices dedicated to intracavitary morcellation in a closed system has been encouraged. PMID- 26902986 TI - Potential adverse effects of antenatal melatonin as a treatment for intrauterine growth restriction: findings in pregnant sheep. AB - BACKGROUND: Intrauterine growth restriction is a condition in which the fetus has a birthweight and/or length <10th percentile for the gestational age. Intrauterine growth restriction can be associated with various causes, among which is low uteroplacental perfusion and chronic hypoxia during gestation. Often, intrauterine growth-restricted fetuses have increased oxidative stress; therefore, agents that decrease oxidative stress and increase utero, placental, and umbilical perfusion have been proposed as a beneficial therapeutic strategy. In this scenario, melatonin acts as an umbilical vasodilator and a potent antioxidant that has not been evaluated in pregnancies under chronic hypoxia that induce fetal growth restriction. However, this neurohormone has been proposed as a pharmacologic therapy for complicated pregnancies. OBJECTIVES: The aim of this study was to determine the effects of prenatal administration of melatonin during the last trimester of pregnancy on the biometry of the growth-restricted lambs because of developmental hypoxia. Further, we aimed to determine melatonin and cortisol levels and oxidative stress markers in plasma of pregnant ewes during the treatment. STUDY DESIGN: High-altitude pregnant sheep received either vehicle (n = 5; 5 mL 1.4% ethanol) or melatonin (n = 7; 10 mg/kg(-1)day(-1) in 5 mL 1.4% ethanol) daily during the last one-third of gestation. Maternal plasma levels of melatonin, cortisol, antioxidant capacity, and oxidative stress were determined along treatment. At birth, neonates were examined, weighed, and measured (biparietal diameter, abdominal diameter, and crown-rump length). RESULTS: Antenatal treatment with melatonin markedly decreased neonatal biometry and weight at birth. Additionally, melatonin treatment increased the length of gestation by 7.5% and shifted the time of delivery. Furthermore, the prenatal treatment doubled plasma levels of melatonin and cortisol and significantly improved the antioxidant capacity of the pregnant ewes. CONCLUSIONS: Our findings indicate that antenatal melatonin induces further intrauterine growth restriction but improves the maternal plasma antioxidant capacity. Additional studies should address the efficiency and safety of antenatal melatonin before clinical attempts on humans. PMID- 26902987 TI - Incidence of posterior reversible encephalopathy syndrome in eclamptic and patients with preeclampsia with neurologic symptoms. AB - BACKGROUND: Posterior reversible encephalopathy syndrome is observed frequently in patients with eclampsia; however, it has also been reported in some patients with preeclampsia. OBJECTIVES: The aim of this study was to determine the incidence of posterior reversible encephalopathy syndrome in patients with preeclampsia and eclampsia and to assess whether these 2 patient groups share similar pathophysiologic backgrounds by comparing clinical and radiologic characteristics. STUDY DESIGN: This was a retrospective cohort study of 4849 pregnant patients. A total of 49 patients with eclampsia and preeclampsia and with neurologic symptoms underwent magnetic resonance imaging and magnetic resonance angiography; 10 patients were excluded from further analysis because of a history of epilepsy or dissociative disorder. The age, parity, blood pressure, and routine laboratory data at the onset of symptoms were also recorded. RESULTS: Among 39 patients with neurologic symptoms, 12 of 13 patients with eclampsia (92.3%) and 5 of 26 patients with preeclampsia (19.2%) experienced the development of posterior reversible encephalopathy syndrome. Whereas age and blood pressure at onset were not significantly different between patients with and without encephalopathy, hematocrit, serum creatinine, aspartate transaminase, alanine transaminase, and lactate dehydrogenase values were significantly higher in patients with posterior reversible encephalopathy syndrome than in those without magnetic resonance imaging abnormalities. In contrast, patients with eclampsia with posterior reversible encephalopathy syndrome did not show any significant differences in clinical and laboratory data compared with patients with preeclampsia with posterior reversible encephalopathy syndrome. In addition to the parietooccipital regions, atypical regions (such as the frontal and temporal lobes), and basal ganglia were also involved in patients with eclampsia and patients with preeclampsia with posterior reversible encephalopathy syndrome. Finally, intraparenchymal hemorrhage was detected in 1 patient with eclampsia, and subarachnoid hemorrhage was observed in 1 patient with preeclampsia. CONCLUSIONS: Although the incidence of posterior reversible encephalopathy syndrome was high in patients with eclampsia, nearly 20% of the patients with preeclampsia with neurologic symptoms also experienced posterior reversible encephalopathy syndrome. The similarities in clinical and radiologic findings of posterior reversible encephalopathy syndrome between the 2 groups support the hypothesis that these 2 patient groups have a shared pathophysiologic background. Thus, magnetic resonance imaging studies should be considered for patients with the recent onset of neurologic symptoms, regardless of the development of eclampsia. PMID- 26902988 TI - Interactions with industry under the Sunshine Act: an example from gynecologic oncology. AB - THE PROBLEM: Clinicians may be unaware that industry payments to physicians are now publicly searchable under the Physician Payments Sunshine Act. Furthermore, the extent of industry's financial involvement in subspecialty practice has not been previously accessible. As an example, 6948 direct, research-unrelated payments totaling $1,957,004 were made to 765 gynecologic oncologists in 2014, the first full year of data available. A total of 153 companies reported at least 1 payment; however, the 10 manufacturers reporting the highest total payment amount accounted for 82% of all payments to physicians. In all, 48 gynecologic oncologists received >$10,000 from manufacturers, accounting for $1,202,228, or 61%, of total payments. A SOLUTION: Obstetrician-gynecologists, including gynecologic oncologists, should be aware of their publicly reported payments from industry and ensure reports' accuracy. Professional organizations, including the Society of Gynecologic Oncology (SGO), should strongly consider proactively developing guidelines regarding interactions with industry for their general memberships. PMID- 26902989 TI - Predicting obstetric anal sphincter injuries in a modern obstetric population. AB - BACKGROUND: Perineal lacerations are common at the time of vaginal delivery and may predispose patients to long-term pelvic floor disorders, such as urinary incontinence and pelvic organ prolapse. Obstetric anal sphincter injuries, which are the most severe form of perineal lacerations, result in disruption of the anal sphincter and, in some cases, the rectal mucosa during vaginal delivery. Long-term morbidity, including pain, pelvic floor disorders, fecal incontinence, and predisposition to recurrent injury at subsequent delivery may result. Despite several studies that have reported risk factors for obstetric anal sphincter injuries, no accurate risk prediction models have been developed. OBJECTIVE: The purpose of this study was to identify risk factors and develop prediction models for perineal lacerations and obstetric anal sphincter injuries. STUDY DESIGN: This was a nested case control study within a retrospective cohort of consecutive term vaginal deliveries at 1 tertiary care facility from 2004-2008. Cases were patients with any perineal laceration that had been sustained during vaginal delivery; control subjects had no lacerations of any severity. Secondary analyses investigated obstetric anal sphincter injury (3rd- to 4(th)-degree laceration) vs no obstetric anal sphincter injury (0 to 2(nd)-degree laceration). Baseline characteristics were compared between groups with the use of the chi-square and Student t test. Adjusted odds ratios and 95% confidence intervals were calculated with the use of multivariable logistic regression. Prediction models were created and model performance was estimated with receiver-operator characteristic curve analysis. Receiver-operator characteristic curves were validated internally with the use of the bootstrap method to correct for bias within the model. RESULTS: Of the 5569 term vaginal deliveries that were recorded during the study period, complete laceration data were available in 5524 deliveries. There were 3382 perineal lacerations and 249 (4.5%) obstetric anal sphincter injuries. After adjusted analysis, significant predictors for laceration included nulliparity, non-black race, longer second stage, nonsmoking status, higher infant birthweight, and operative delivery. Private health insurance, labor induction, pushing duration, and regional anesthesia were not statistically significant in adjusted analyses. Significant risk factors for obstetric anal sphincter injury were similar to predictors for any laceration; nulliparity and operative vaginal delivery had the highest predictive value. Area under the curve for the predictive ability of the models was 0.70 for overall perineal laceration, and 0.83 for obstetric anal sphincter injury. When limited to primiparous patients, 1996 term vaginal deliveries were recorded. One hundred ninety-two women sustained an obstetric anal sphincter injury; 1796 women did not. After adjusted analysis, significant predictors for laceration included non-black race, age, obesity, and nonsmoking status. In secondary analyses, significant predictors for obstetric anal sphincter injury included non-black race, nonsmoking status, longer duration of pushing, operative vaginal delivery, and infant birthweight. Area under the curve for the predictive ability of the models was 0.60 for any laceration and 0.77 for obstetric anal sphincter injury. CONCLUSIONS: Significant risk factors for sustaining any laceration and obstetric anal sphincter injury during vaginal deliveries were identified. These results will help identify clinically at-risk patients and assist providers in counseling patients about modifications to decrease these risks. PMID- 26902990 TI - Diagnosis and antenatal management of congenital cytomegalovirus infection. AB - Congenital cytomegalovirus (CMV) is the most common viral infection, affecting nearly 40,000 infants each year in the United States. Of seronegative women, 1-4% will acquire a primary infection during pregnancy, and the majority of these women will be asymptomatic. Prior maternal exposure to CMV does not preclude neonatal infection. The purpose of this document is to review diagnosis of primary maternal CMV infection, diagnosis of fetal CMV infection, and whether antenatal therapy is warranted. We recommend the following: (1) that women with a diagnosis of primary CMV infection in pregnancy be advised that the risk of congenital infection is 30-50%, on average, and that the severity of infection varies widely (Best Practice); (2) for women suspected of having primary CMV infection in pregnancy, we recommend that diagnosis should be either by IgG seroconversion or with positive CMV IgM, positive IgG, and low IgG avidity (grade 1B); (3) amniocentesis is the best option as a prenatal diagnostic tool to detect fetal congenital CMV infection, performed >21 weeks of gestation and >6 weeks from maternal infection (grade 1C); (4) we do not recommend routine screening of all pregnant women for evidence of primary CMV infection at this time (grade 1B); and (5) we do not recommend antenatal treatment with ganciclovir or valacyclovir; and we recommend that any antenatal therapy, either with antivirals or CMV hyperimmune globulin, should only be offered as part of a research protocol (Best Practice). PMID- 26902991 TI - Biomarkers of in vivo fluorescence imaging in allergic airway inflammation. AB - Airway inflammation is a central component of the manifestation of asthma but is relatively inaccessible to study. Current imaging techniques such as X-ray CT, MRI, and PET, have advanced noninvasive research on pulmonary diseases. However, these techniques mainly facilitate the anatomical or structural assessment of the diseased lung and/or typically use radioactive agents. In vivo fluorescence imaging is a novel method for noninvasive, real-time, and specific monitoring of lung airway inflammation, which is particularly important to gain a further understanding asthma. Compared to conventional techniques, fluorescent imaging has the advantages of rapid feedback, as well as high sensitivity and resolution. Recently, there has been an increase in the identification of biomarkers, including matrix metalloproteinases, cathepsins, selectins, folate receptor-beta, nanoparticles, as well as sialic acid-binding immunoglobulin-like lectin-F to assess the level of airway inflammation in asthma. Recent advances in our understanding of these biomarkers as molecular probes for in vivo imaging are discussed in this review. PMID- 26902992 TI - The role of danger signals and ectonucleotidases in acute graft-versus-host disease. AB - Allogeneic hematopoietic cell transplantation (allo-HCT) represents the only curative treatment approach for many patients with benign or malignant diseases of the hematopoietic system. However, post-transplant morbidity and mortality are significantly increased by the development of acute graft-versus-host disease (GvHD). While alloreactive T cells act as the main cellular mediator of the GvH reaction, recent evidence suggests a critical role of the innate immune system in the early stages of GvHD initiation. Danger-associated molecular patterns released from the intracellular space as well as from the extracellular matrix activate antigen-presenting cells and set pro-inflammatory pathways in motion. This review gives an overview about danger signals representing therapeutic targets with a clinical perspective with a particular focus on extracellular nucleotides and ectonucleotidases. PMID- 26902993 TI - Deciphering IgM interference in IgG anti-HLA antibody detection with flow beads assays. AB - In flow beads assays, the interference of IgM for IgG anti-HLA antibodies detection is not precisely understood. Using the screening flow beads assay for class I HLA antibodies, we analyzed the binding of two IgG mAbs, the anti-class I HLA W6/32 and an anti-beta-2-microglobulin, in the presence of an anti-beta-2 microglobulin IgM mAb. In neat serum, the IgM mAb impaired the detection of both IgG. In EDTA-treated serum, the interference was stronger for the anti-beta-2 microglobulin IgG than for W6/32, in agreement with the finding in surface plasmon resonance that this IgM competed with the anti-beta-2-microglobulin IgG but not with W6/32. The IgM interference was higher in neat than in EDTA-treated serum for both IgG mAbs. The IgM interference was also analyzed with class II single antigen flow beads and sera from two kidney recipients containing IgG and IgM donor specific antibodies. Anti-HLA IgG detection was partially corrected by EDTA, and restored by IgM inactivation with DTT, confirming the results observed with the mAbs. Therefore, three mechanisms can explain the IgM interference for IgG anti-HLA antibodies in flow beads assays: direct competition for antigen, steric hindrance and complement activation. PMID- 26902994 TI - Using EasyMatch(r) to anticipate the identification of an HLA identical unrelated donor: A validated efficient time and cost saving method. AB - In the absence of an HLA matched familial donor, a search for an unrelated donor or cord blood unit is initiated through worldwide registries. Although a first look-up on available HLA information of donors in the "book" at BMDW (Bone Marrow Donor Worldwide) can provide a good estimation of the number of compatible donors, the variety of resolution typing levels requires confirmatory typing (CT) which are expensive and time consuming. In order to help recipient centers in their work. The French donor registry (France Greffe de Moelle/Agence de la Biomedecine) has recently developed a software program called "EasyMatch(r)" that uses haplotype frequencies to compute the likelihood of phenotypic match in donors according to various typing resolution levels. The goal of our study is to report a single monocentric user-experience with EasyMatch(r), demonstrating that its routine use reduced the cost and the delay of the donor search in our center, allowing the definition of a new strategy to search compatible unrelated donors. The strategy was first established on a retrospective cohort of 217 recipients (185 adults and 32 children=before score) and then validated on a prospective cohort of 171 recipients (160 adults and 11 children=after score). For all patients, we calculated the delay between the registration day and the donor identification day, and the number of CT requested to the donor centre. Considering both groups, we could observe a significant decrease of the number of CT from 8 to 2 (p<0,001), and a significant decrease of the median delay to identify a suitable donor from 43 to 31days (p<0.0001). EasyMatch(r) estimates the number of potentially identical donors, but doesn't foresee availability of the donors. It provides us an easy tracking of mismatches, an estimation of the number of potential donors, the selection of population following ethnic origin of patients and a high prediction when probability is high or low. It affords a new approach of donor search in our daily work and improves the efficiency in the great challenge of the compatible donor identification. PMID- 26902997 TI - What we don't know about osteoporosis. PMID- 26902996 TI - Polymorphisms of the FTO and MTHFR genes and vascular, inflammatory and metabolic marker levels in postmenopausal women. AB - OBJECTIVE: To determine the prevalence of three single nucleotide polymorphisms (SNPs) in postmenopausal women with and without the metabolic syndrome (METS) and to explore levels of circulating biomarkers of inflammation, vascular and metabolic dysfunction according to SNP genotypes. METHODS: DNA was extracted from the whole blood of 192 natural postmenopausal women (40 to 65 years) screened for the METS and tested for three gene SNPs related to obesity: the fat mass obesity (FTO: rs9939609) and the methylenetetrahydrofolate reductase (MTHFR: C677T and A1298C). Blood levels of angiopoietin, IL-8, sFASL, IL-6, TNF-alpha, sCD40L, PAI 1, u-PA, leptin, adiponectin, resistin, ghrelin, visfatin, adipsin and insulin were measured in a subgroup, with and without the METS, using multiplex technology (n = 100) and compared according to SNP genotypes. RESULTS: Genotype frequency of the three studied SNPs did not differ in relation to the presence of the METS. However, genotypes CT+TT (C677T) and AT (rs9939609) were more prevalent in women with high triglyceride levels. Pooled sub-analysis (n = 100) found that median sCD40L and visfatin levels were higher in women with genotypes AT+TT (rs9939609) as compared to AA (1178 vs. 937.0 pg/mL and 0.93 vs. 0.43 ng/mL, respectively, p < 0.05). CONCLUSION: Two SNP genotypes related to obesity were more prevalent in women with abnormal triglyceride levels and two vascular and inflammatory serum markers were higher in relation to the rs9939609 SNP. PMID- 26902995 TI - The Structural Basis of Oncogenic Mutations G12, G13 and Q61 in Small GTPase K Ras4B. AB - Ras mediates cell proliferation, survival and differentiation. Mutations in K Ras4B are predominant at residues G12, G13 and Q61. Even though all impair GAP assisted GTP -> GDP hydrolysis, the mutation frequencies of K-Ras4B in human cancers vary. Here we aim to figure out their mechanisms and differential oncogenicity. In total, we performed 6.4 MUs molecular dynamics simulations on the wild-type K-Ras4B (K-Ras4B(WT)-GTP/GDP) catalytic domain, the K-Ras4B(WT)-GTP GAP complex, and the mutants (K-Ras4B(G12C/G12D/G12V)-GTP/GDP, K-Ras4B(G13D) GTP/GDP, K-Ras4B(Q61H)-GTP/GDP) and their complexes with GAP. In addition, we simulated 'exchanged' nucleotide states. These comprehensive simulations reveal that in solution K-Ras4B(WT)-GTP exists in two, active and inactive, conformations. Oncogenic mutations differentially elicit an inactive-to-active conformational transition in K-Ras4B-GTP; in K-Ras4B(G12C/G12D)-GDP they expose the bound nucleotide which facilitates the GDP-to-GTP exchange. These mechanisms may help elucidate the differential mutational statistics in K-Ras4B-driven cancers. Exchanged nucleotide simulations reveal that the conformational transition is more accessible in the GTP-to-GDP than in the GDP-to-GTP exchange. Importantly, GAP not only donates its R789 arginine finger, but stabilizes the catalytically-competent conformation and pre-organizes catalytic residue Q61; mutations disturb the R789/Q61 organization, impairing GAP-mediated GTP hydrolysis. Together, our simulations help provide a mechanistic explanation of key mutational events in one of the most oncogenic proteins in cancer. PMID- 26902999 TI - Z3 parafermionic chain emerging from Yang-Baxter equation. AB - We construct the 1D Z3 parafermionic model based on the solution of Yang-Baxter equation and express the model by three types of fermions. It is shown that the Z3 parafermionic chain possesses both triple degenerate ground states and non trivial topological winding number. Hence, the Z3 parafermionic model is a direct generalization of 1D Z2 Kitaev model. Both the Z2 and Z3 model can be obtained from Yang-Baxter equation. On the other hand, to show the algebra of parafermionic tripling intuitively, we define a new 3-body Hamiltonian H123 based on Yang-Baxter equation. Different from the Majorana doubling, the H123 holds triple degeneracy at each of energy levels. The triple degeneracy is protected by two symmetry operators of the system, omega-parity P [formula in text] and emergent parafermionic operator Gamma, which are the generalizations of parity PM and emergent Majorana operator in Lee-Wilczek model, respectively. Both the Z3 parafermionic model and H123 can be viewed as SU(3) models in color space. In comparison with the Majorana models for SU(2), it turns out that the SU(3) models are truly the generalization of Majorana models resultant from Yang-Baxter equation. PMID- 26903000 TI - Mechanism of Protein Molecule Isolation by IR Laser Ablation of Droplet Beam. AB - Gas-phase isolation of bovine serum albumin (BSA) from aqueous solutions is performed by IR laser ablation of a droplet beam. Multiply charged BSA ions (positive and negative) were produced by the IR laser irradiation onto a droplet beam of aqueous BSA solutions with various pH values prepared by addition of hydrochloric acid or sodium hydroxide to the solution. The isolation mechanism was discussed based on the charge state of the isolated BSA ions. A nanodroplet model explains the gas-phase charge distribution of the BSA ions. This study provides a fundamental basis for further studies of a wide variety of biomolecules in the gas phase isolated directly from solution. PMID- 26902998 TI - The role of WWOX polymorphisms on COPD susceptibility and pulmonary function traits in Chinese: a case-control study and family-based analysis. AB - Single nucleotide polymorphisms (SNPs) in the WW domain containing oxidoreductase (WWOX) gene were recently identified to be quantitative trait loci for lung function and thus likely to be susceptible biomarkers for COPD. However, the associations between WWOX SNPs and COPD risk are still unclear. Here, by conducting a two-center case-control study including 1511 COPD cases and 1677 controls and a family-based analysis comprising 95 nuclear pedigrees, we tested the associations between five SNPs that are rs10220974C >T, rs3764340C >G, rs12918952G >A, rs383362G >T, rs12828G >A of WWOX and COPD risk as well as the hereditary inclination of these loci among COPD families. We found that the SNP rs383362G >T was significantly associated with an increased risk of COPD in a T allele-number dependent-manner (OR = 1.30, 95%CI = 1.11-1.52). The T allele was more prone to over transmit to sick children and sibs than the G allele (Z = 2.900, P = 0.004). Moreover, the forced expiratory volume in one second/forced vital capacity (FEV1/FVC), FEV1/predicted-FEV1 and annual FEV1 also significantly decreased in the rs383362T carriers compared to the rs383362GG carriers. For other SNPs, no significant association was observed for COPD and pulmonary function. Taken together, our data demonstrated that the SNP rs383362G >T of WWOX plays a role in COPD inheritance. PMID- 26903001 TI - Percutaneous Ankle Reconstruction of Lateral Ligaments (Perc-Anti RoLL). PMID- 26903002 TI - Sex Differences in Clinical Profiles and Quality of Care Among Patients With ST Segment Elevation Myocardial Infarction From 2001 to 2011: Insights From the China Patient-Centered Evaluative Assessment of Cardiac Events (PEACE) Retrospective Study. AB - BACKGROUND: China is experiencing a marked increase in ST-segment elevation myocardial infarction hospitalizations, with 30% occurring among women and higher risk of in-hospital death in relatively younger age groups (<70). Yet, little is known about sex differences in ST-segment elevation myocardial infarction presentation and management. METHODS AND RESULTS: In a nationally representative sample of patients with ST-segment elevation myocardial infarction admitted to 162 Chinese hospitals in 2001, 2006, and 2011, we examined sex differences in hospitalization rates, clinical profiles, and quality of care. Among 11 986 patients, the proportion of women was unchanged between 2001 and 2011. The estimated national rates of hospital admission per 100 000 people increased from 4.6 in 2001 to 18.0 in 2011 among men (3.9-fold increase) and from 1.9 to 8.0 among women (4.2-fold increase) (Ptrend<0.0001). The median age of women increased from 68 years in 2001 to 72 years in 2011 (Ptrend<0.001); however, there was no age change in men (63 years in 2011) (Ptrend=0.48). After accounting for age, women had a higher frequency of comorbidities. Although there were significant sex differences in the time interval of >12 hours between symptom onset and admission time in 2001, since 2006 delays in presentation were comparable between women and men. Fewer women without contraindications received evidence-based therapies than men, including reperfusion (57.5% versus 44.2%), early aspirin (88.8% versus 85.9%), and clopidogrel (56.9% versus 52.5%, P<0.001 for all) and the differences were largely unchanged over time. CONCLUSIONS: Women experienced a higher increase in hospitalization rates for ST-segment elevation myocardial infarction in China between 2001 and 2011 and were less likely to receive evidence-based therapies, especially reperfusion. In addition to efforts to improve quality of care generally, understanding the reasons for this sex disparity and addressing these differences in care should be a priority. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01624883. PMID- 26903003 TI - Trimethylamine N-Oxide Promotes Vascular Inflammation Through Signaling of Mitogen-Activated Protein Kinase and Nuclear Factor-kappaB. AB - BACKGROUND: The choline-derived metabolite trimethylamine N-oxide (TMAO) has been demonstrated to contribute to atherosclerosis and is associated with coronary artery disease risk. METHODS AND RESULTS: We explored the impact of TMAO on endothelial and smooth muscle cell function in vivo, focusing on disease-relevant outcomes for atherogenesis. Initially, we observed that aortas of LDLR(-/-) mice fed a choline diet showed elevated inflammatory gene expression compared with controls. Acute TMAO injection at physiological levels was sufficient to induce the same inflammatory markers and activate the well-known mitogen-activated protein kinase, extracellular signal-related kinase, and nuclear factor-kappaB signaling cascade. These observations were recapitulated in primary human aortic endothelial cells and vascular smooth muscle cells. We also found that TMAO promotes recruitment of activated leukocytes to endothelial cells. Through pharmacological inhibition, we further showed that activation of nuclear factor kappaB signaling was necessary for TMAO to induce inflammatory gene expression in both of these relevant cell types as well as endothelial cell adhesion of leukocytes. CONCLUSIONS: Our results suggest a likely contributory mechanism for TMAO-dependent enhancement in atherosclerosis and cardiovascular risks. PMID- 26903005 TI - Gradual Carotid Artery Stenosis in Mice Closely Replicates Hypoperfusive Vascular Dementia in Humans. AB - BACKGROUND: Existing rodent models of vascular cognitive impairment (VCI) show abrupt changes in cerebral blood flow (CBF) and do not reliably replicate the clinical pathogenesis of VCI. We therefore aimed to develop a mouse model of VCI where CBF is gradually reduced, followed by subsequent progressive motor and cognitive impairment, after surgical intervention. METHODS AND RESULTS: Adult C57BL/6J male mice were subjected to gradual common carotid artery stenosis (GCAS) surgery by using an ameroid constrictor vessel-constricting device with an inner diameter of 0.75 mm. The common carotid arteries narrowed gradually after gradual constriction of ameroid constrictors over 28 days after GCAS, with subsequent 79.3% area stenosis as a result of smooth muscle cell proliferation and macrophage infiltration in the tunica intima. The 28-day survival rate was 91%. Arterial spin labeling demonstrated gradual and continuous reduction of cortical and subcortical CBF (ratio to the preoperative value) to 54.6% and 51.5%, respectively, over 28 days. However, magnetic resonance angiography showed increment of collateral flow signals in the leptomeningeal artery. Rarefaction and proliferation of astrocytes and microglia, with loss of oligodendrocytes, were found in the white matter at 32 days. Hippocampal neuronal loss was observed in only 25% of GCAS mice, consistent with lack of abnormalities in the Morris water maze test. The rotarod test showed motor impairment, and the Y-maze test showed working memory deficits. CONCLUSIONS: The GCAS model successfully generated gradual and continuous CBF reduction over 28 days, with replication of key histological, radiological, and behavioral features associated with cerebral hypoperfusion leading to VCI. PMID- 26903004 TI - Varenicline and Adverse Cardiovascular Events: A Systematic Review and Meta Analysis of Randomized Controlled Trials. AB - BACKGROUND: Varenicline is an efficacious smoking-cessation drug. However, previous meta-analyses provide conflicting results regarding its cardiovascular safety. The publication of several new randomized controlled trials (RCTs) provides an opportunity to reassess this potential adverse drug reaction. METHODS AND RESULTS: We searched MEDLINE, EMBASE, and the Cochrane Library for RCTs that compare varenicline with placebo for smoking cessation. RCTs reporting cardiovascular serious adverse events and/or all-cause mortality during the treatment period or within 30 days of treatment discontinuation were eligible for inclusion. Relative risks (RRs) with 95% CIs were generated by using DerSimonian Laird random-effects models. Thirty-eight RCTs met our inclusion criteria (N=12 706). Events were rare in both varenicline (57/7213) and placebo (43/5493) arms. No difference was observed for cardiovascular serious adverse events when comparing varenicline with placebo (RR 1.03, 95% CI 0.72-1.49). Similar findings were obtained when examining cardiovascular (RR 1.04, 95% CI 0.57-1.89) and noncardiovascular patients (RR 1.03, 95% CI 0.64-1.64). Deaths were rare in both varenicline (11/7213) and placebo (9/5493) arms. Although 95% CIs were wide, pooling of all-cause mortality found no difference between groups (RR 0.88, 95% CI 0.50-1.52), including when stratified by participants with (RR 1.24, 95% CI 0.40-3.83) and without (RR 0.77, 95% CI 0.40-1.48) cardiovascular disease. CONCLUSIONS: We found no evidence that varenicline increases the rate of cardiovascular serious adverse events. Results were similar among those with and without cardiovascular disease. Given varenicline's efficacy as a smoking cessation drug and the long-term cardiovascular benefits of cessation, it should continue to be prescribed for smoking cessation. PMID- 26903006 TI - Cardiovascular Event Prediction and Risk Reclassification by Coronary, Aortic, and Valvular Calcification in the Framingham Heart Study. AB - BACKGROUND: We determined whether vascular and valvular calcification predicted incident major coronary heart disease, cardiovascular disease (CVD), and all cause mortality independent of Framingham risk factors in the community-based Framingham Heart Study. METHODS AND RESULTS: Coronary artery calcium (CAC), thoracic and abdominal aortic calcium, and mitral or aortic valve calcium were measured by cardiac computed tomography in participants free of CVD. Participants were followed for a median of 8 years. Multivariate Cox proportional hazards models were used to determine association of CAC, thoracic and abdominal aortic calcium, and mitral and aortic valve calcium with end points. Improvement in discrimination beyond risk factors was tested via the C-statistic and net reclassification index. In this cohort of 3486 participants (mean age 50+/-10 years; 51% female), CAC was most strongly associated with major coronary heart disease, followed by major CVD, and all-cause mortality independent of Framingham risk factors. Among noncoronary calcifications, mitral valve calcium was associated with major CVD and all-cause mortality independent of Framingham risk factors and CAC. CAC significantly improved discriminatory value beyond risk factors for coronary heart disease (area under the curve 0.78-0.82; net reclassification index 32%, 95% CI 11-53) but not for CVD. CAC accurately reclassified 85% of the 261 patients who were at intermediate (5-10%) 10-year risk for coronary heart disease based on Framingham risk factors to either low risk (n=172; no events observed) or high risk (n=53; observed event rate 8%). CONCLUSIONS: CAC improves discrimination and risk reclassification for major coronary heart disease and CVD beyond risk factors in asymptomatic community dwelling persons and accurately reclassifies two-thirds of the intermediate-risk population. PMID- 26903007 TI - Impaired retinal microcirculation in multiple sclerosis. AB - BACKGROUND: The transparent ocular structure enables quantitative analysis of microvasculature of retina, a neuronal tissue affected by multiple sclerosis (MS). OBJECTIVE: The aim of this study was to determine whether the retinal blood flow velocity and flow volume at the macula are impaired in patients with relapsing remitting multiple sclerosis (RRMS). METHODS: A total of 17 RRMS patients and 17 age- and gender-matched healthy subjects were assessed. A retinal function imager was used to measure the blood flow velocity of retinal arterioles and venules and to calculate the total perifoveal blood flow volume. RESULTS: The blood flow velocities of the retinal arterioles (3.34 +/- 0.89 mm/s) and venules (2.61 +/- 0.6 mm/s) were significantly lower in MS patients than normal subjects (arteriole: 4.10 +/- 0.87 mm/s; venule: 3.22 +/- 0.65 mm/s, both p = 0.01). In addition, the total perifoveal blood flow volume in arterioles (3.74 +/- 1.64 nL/s) and venules (3.81 +/- 1.60 nL/s) were significantly lower in MS patients than in normal subjects (arteriole: 4.87 +/- 1.41 nL/s, p = 0.02; venule: 4.71 +/ 1.64 nL/s, p = 0.04). CONCLUSION: The impaired retinal microcirculation in RRMS patients indicates microvascular dysfunction in MS. PMID- 26903008 TI - Peripartum depression in parents with multiple sclerosis and psychiatric disorders in children. AB - BACKGROUND: Although many individuals with multiple sclerosis (MS) experience depression, there are no studies on the frequency and effect of peripartum depression among parents with MS. OBJECTIVE: To examine the frequency of peripartum depression in individuals with MS and its potential association with children's psychiatric disorders. METHODS: We conducted a cohort study in British Columbia, Canada, using linked health databases, of parents with MS and their children, and age-matched unaffected parent-child dyads. The diagnosis of peripartum depression, MS and psychiatric disorders in children was based on information from hospital admission, physician visit and drug prescription claims. RESULTS: Peripartum depression was significantly more common among MS parents (n = 360) versus unaffected (n = 1207) parents (25.8% vs 18.5%, p value 0.02), especially among MS affected fathers versus unaffected fathers (25.7% vs 10.2%, p value < 0.001). The incidence of psychiatric disorders in children was 3.3 and 2.7 per 100 child-years among children with and without an MS parent, respectively. The rate of psychiatric disorders was significantly higher in children with an MS parent (vs without, hazard ratio (HR): 1.34; 95% confidence interval (CI): 1.03-1.74) and among children with parents who had peripartum depression (HR: 1.87; 95% CI: 1.36-2.55). CONCLUSION: Parental MS is associated with a higher risk of peripartum depression and increases the risk of psychiatric disorders in children. PMID- 26903009 TI - Fabrication of Eu-doped Gd(OH)3 Nanorods with Enhanced Magnetic- Resonance and Luminescence Imaging. AB - BACKGROUND: Multimodal bio-imaging is a new technique with more than one imaging modality. Eu3+ doping can tailor the multi-functions of Gd-based nanorods (NRs) to obtain the resolution the imaging at the cellular level. Silk fibroin with His and Lys can induce to fabricate metal compounds particles. However, one-step preparation of SFP-linked Eu-Gd(OH)3 NRs with cyto-compatibility is very challenging. METHODS: Eu-doped Gd(OH)3 nanorods with silk fibroin peptides (SFP NRs) are synthesized via a simple and feasible biomimetic method in the assistance of SFPs. RESULTS: The measurement results showed that these hexagonal crystal NRs possessed 300 nm of the length. Compared with pure NRs, SFP-NRs exhibited better in vitro T1 signal-enhancement of magnetic resonance (MR) imaging due to their higher ratio of Eu and Gd and SFP coating on their surface, and the longitudinal relaxivity r1 value is 2.57 (Gd mM.s)-1 under a 7.0 T MR imaging system. Furthermore, a series of in vivo T1-weighted MR images between pre- and post-injection in tumor regions for 9 h indicated that average intensity of post-injection of SF-NRs was enhanced to 68%, higher the increased value of pure NRs (19.6%), but also SFP-NRs showed the good luminescence labeling of viable cell in the fluorescence observation. CONCLUSION: These results indicate that Eu-doped SFP-NRs have potential as T1 MR imaging contrast agents and optical imaging probe in tumor-detection field. PMID- 26903010 TI - Complement receptor activity of recombinant porcine CR1-like protein expressed in a eukaryotic system. AB - Primate complement receptor type 1 (CR1) protein, a single-chain transmembrane glycoprotein, plays an important role in immune adherence and clearing complement opsonized immune complexes. Here, the mRNA of the porcine primate-like complement receptor (CR1-like) gene was analyzed, and two domain sequences with potential functions were cloned into the pwPICZalpha vector for expression in Pichia pastoris. The recombinant proteins were purified with both Protein Pure Ni-NTA resin and strong anion exchange resin. The activities of the purified recombinant proteins were evaluated by SDS-PAGE, western blotting, and complement receptor assays. The results indicated that two domains of the CR1-like protein, CCP36 and CCP811 with molecular weights of 29.8 kDa and 30 kDa, respectively, were successfully expressed in P. pastoris. These two recombinant proteins possess some of the functions of the primate CR1 protein. Using these two proteins coupled with an antibody blocking technique, we also showed that CR1-like is expressed on natural porcine erythrocytes. PMID- 26903011 TI - Biogeography of bacteriophages at four hydrothermal vent sites in the Antarctic based on g23 sequence diversity. AB - In this study, which was carried out within the ChEsSO consortium project (Chemosynthetically driven ecosystems south of the Polar Front), we sampled two hydrothermal vent sites on the East Scotia Ridge, Scotia Sea, one in the Kemp Caldera, South Sandwich Arc and one in the Bransfield Strait, north-west of the Antarctic Peninsula, which exhibit strong differences in their chemical characteristics. We compared a subset of their bacteriophage population by Sanger and 454-sequencing of g23, which codes for the major capsid protein of T4likeviruses. We found that the sites differ vastly in their bacteriophage diversity, which reflects the differences in the chemical conditions and therefore putatively the differences in microbial hosts living at these sites. Comparing phage diversity in the vent samples to other aquatic samples, the vent samples formed a distinct separate cluster, which also included the non-vent control samples that were taken several hundred meters above the vent chimneys. This indicates that the influence of the vents on the microbial population and therefore also the bacteriophage population extends much further than anticipated. PMID- 26903012 TI - Butanol formation from gaseous substrates. AB - Mostly, butanol is formed as a product by saccharolytic anaerobes, employing the so-called ABE fermentation (for acetone-butanol-ethanol). However, this alcohol can also be produced from gaseous substrates such as syn(thesis) gas (major components are carbon monoxide and hydrogen) by autotrophic acetogens. In view of economic considerations, a biotechnological process based on cheap and abundant gases such as CO and CO2 as a carbon source is preferable to more expensive sugar or starch fermentation. In addition, any conflict for use of substrates that can also serve as human nutrition is avoided. Natural formation of butanol has been found with, e.g. Clostridium carboxidivorans, while metabolic engineering for butanol production was successful using, e.g. C. ljungdahlii. Production of butanol from CO2 under photoautotrophic conditions was also possible by recombinant DNA construction of a respective cyanobacterial Synechococcus sp. PCC 7942 strain. PMID- 26903013 TI - Evaluation of polymorphisms in pbp4 gene and genetic diversity in penicillin resistant, ampicillin-susceptible Enterococcus faecalis from hospitals in different states in Brazil. AB - The aim of the present study was to verify whether penicillin-resistant, ampicillin-susceptible Enterococcus faecalis (PRASEF) occurred in Brazil prior to the beginning of the 21st century, and to verify whether ampicillin susceptibility can predict susceptibility to other beta-lactams in E. faecalis with this inconsistent phenotype. The presence of polymorphisms in the pbp4 gene and genetic diversity among the isolates were investigated. Of 21 PRASEF analyzed, 5 (23.8%) and 4 (19.0%) were imipenem and piperacillin resistant simultaneously by disk diffusion and broth dilution respectively, contradicting the current internationally accepted standards of susceptibility testing. Sequencing of pbp4 gene revealed an amino acid substitution (Asp-573->Glu) in all PRASEF isolates but not in the penicillin-susceptible, ampicillin-susceptible E. faecalis. Most PRASEF (90.5%) had related pulsed-field gel electrophoresis profiles, but were different from other PRASEF described to date. Results demonstrate that penicillin-resistant, ampicillin-susceptible phenotype was already a reality in the 1990s in E. faecalis isolates in different Brazilian states, and some of these isolates were also imipenem- and piperacillin resistant; therefore, internationally accepted susceptibility criteria cannot be applied to these isolates. According to pbp4 gene sequencing, this study suggests that a specific amino acid substitution in pbp4 gene found in all PRASEF analyzed is associated with penicillin resistance. PMID- 26903014 TI - Vestibular schwannoma and pituitary adenoma in the same patient: coincidence or novel clinical association? AB - Over the years the authors have evaluated a number of patients with vestibular schwannomas (VS) who have also been diagnosed with a pituitary adenoma (PA). No associations between these tumors have been established to date. The objective of the current study is to investigate the epidemiological association between VS and PA via a population-based study and to supplement these data with a retrospective case series of 12 patients who were evaluated at the authors' center over the past 15 years. An analysis of the Surveillance, Epidemiology, and End Results database including all patients identified with a diagnosis of VS and/or PA was performed. A comparison between the observed and expected annual incidence was calculated and population differences between those with VS + PA were compared with single tumor populations. 9888 patients with VS and 26,577 patients with PA were identified among 822.9 million person-years. Within these populations, 31 patients were diagnosed with both tumor types. Overall, 1 in every 319 patients with VS was also diagnosed with a PA. The average annual incidence for VS was 1.2 per 100,000 persons per year while the average PA rate was 3.2 per 100,000 persons per year. The observed rate of co-incident VS and PA was greater than what is expected by chance alone assuming independence. The cohort of patients with coexisting VS and PA were older and more commonly male compared to VS-only or PA-only groups. These data strongly suggest that a common environmental or genetic predisposition exists for VS and PA development. Further study of this population may help elucidate the cause of tumorigenesis in a subset of patients with seemingly sporadic tumors. PMID- 26903015 TI - Cationizable lipid micelles as vehicles for intraarterial glioma treatment. AB - The relative abundance of anionic lipids on the surface of endothelia and on glioma cells suggests a workable strategy for selective drug delivery by utilizing cationic nanoparticles. Furthermore, the extracellular pH of gliomas is relatively acidic suggesting that tumor selectivity could be further enhanced if nanoparticles can be designed to cationize in such an environment. With these motivating hypotheses the objective of this study was to determine whether nanoparticulate (20 nm) micelles could be designed to improve their deposition within gliomas in an animal model. To test this, we performed intra-arterial injection of micelles labeled with an optically quantifiable dye. We observed significantly greater deposition (end-tissue concentration) of cationizable micelles as compared to non-ionizable micelles in the ipsilateral hemisphere of normal brains. More importantly, we noted enhanced deposition of cationizable as compared to non-ionizable micelles in glioma tissue as judged by semiquantitative fluorescence analysis. Micelles were generally able to penetrate to the core of the gliomas tested. Thus we conclude that cationizable micelles may be constructed as vehicles for facilitating glioma-selective delivery of compounds after intraarterial injection. PMID- 26903016 TI - Omitted Author Affiliation. PMID- 26903018 TI - A Shocking Development in a Young Male Athlete With Chest Pain. PMID- 26903019 TI - ECG Response: February 23, 2016. PMID- 26903017 TI - Resource Effective Strategies to Prevent and Treat Cardiovascular Disease. AB - Cardiovascular disease (CVD) is the leading cause of global deaths, with the majority occurring in low- and middle-income countries. The primary and secondary prevention of CVD is suboptimal throughout the world, but the evidence-practice gaps are much more pronounced in low- and middle-income countries. Barriers at the patient, healthcare provider, and health system level prevent the implementation of optimal primary and secondary prevention. Identification of the particular barriers that exist in resource-constrained settings is necessary to inform effective strategies to reduce the identified evidence-practice gaps. Furthermore, targeting modifiable factors that contribute most significantly to the global burden of CVD, including tobacco use, hypertension, and secondary prevention for CVD, will lead to the biggest gains in mortality reduction. We review a select number of novel, resource-efficient strategies to reduce premature mortality from CVD, including (1) effective measures for tobacco control, (2) implementation of simplified screening and management algorithms for those with or at risk of CVD, (3) increasing the availability and affordability of simplified and cost-effective treatment regimens including combination CVD preventive drug therapy, and (4) simplified delivery of healthcare through task sharing (nonphysician health workers) and optimizing self-management (treatment supporters). Developing and deploying systems of care that address barriers related to the above will lead to substantial reductions in CVD and related mortality. PMID- 26903020 TI - Surgically Constructed Double-Outlet Right Ventricle. PMID- 26903021 TI - Notes From the Incoming Editor. PMID- 26903022 TI - Left Ventricular Lipomatous Hamartoma Mimicking a Calcified Amorphous Tumor. PMID- 26903023 TI - Letter by Tuncez et al Regarding Article, "The Forgotten Valve: Isolated Severe Tricuspid Valve Stenosis". PMID- 26903024 TI - Letter by Guo et al Regarding Article, "Endovascular Versus External Targeted Temperature Management for Patients With Out-of-Hospital Cardiac Arrest: A Randomized, Controlled Study". PMID- 26903025 TI - Response to Letter Regarding Article, "Endovascular Versus External Targeted Temperature Management for Patients With Out-of-Hospital Cardiac Arrest: A Randomized, Controlled Study". PMID- 26903026 TI - Letter by Archer Regarding Article, "Southern Dietary Pattern is Associated With Hazard of Acute Coronary Heart Disease in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study". PMID- 26903028 TI - Correction. PMID- 26903027 TI - Response to Letter Regarding Article, "Southern Dietary Pattern is Associated With Hazard of Acute Coronary Heart Disease in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study". PMID- 26903029 TI - Correction. PMID- 26903030 TI - DNA Strand Breaks in Mitotic Germ Cells of Caenorhabditis elegans Evaluated by Comet Assay. AB - DNA damage responses are important for the maintenance of genome stability and the survival of organisms. Such responses are activated in the presence of DNA damage and lead to cell cycle arrest, apoptosis, and DNA repair. In Caenorhabditis elegans, double-strand breaks induced by DNA damaging agents have been detected indirectly by antibodies against DSB recognizing proteins. In this study we used a comet assay to detect DNA strand breaks and to measure the elimination of DNA strand breaks in mitotic germline nuclei of C. elegans. We found that C. elegans brc-1 mutants were more sensitive to ionizing radiation and camptothecin than the N2 wild-type strain and repaired DNA strand breaks less efficiently than N2. This study is the first demonstration of direct measurement of DNA strand breaks in mitotic germline nuclei of C. elegans. This newly developed assay can be applied to detect DNA strand breaks in different C. elegans mutants that are sensitive to DNA damaging agents. PMID- 26903031 TI - Four emerging arboviral diseases in North America: Jamestown Canyon, Powassan, chikungunya, and Zika virus diseases. AB - Arthropod-borne viruses, or arboviruses, are viruses that are transmitted through the bites of mosquitoes, ticks, or sandflies. There are numerous arboviruses throughout the world capable of causing human disease spanning different viral families and genera. Recently, Jamestown Canyon, Powassan, chikungunya, and Zika viruses have emerged as increasingly important arboviruses that can cause human disease in North America. Unfortunately, there are currently no proven disease modifying therapies for these arboviral diseases, so treatment is largely supportive. Given there are also no commercially available vaccines for these four arboviral infections, prevention is the key. To prevent mosquito or tick bites that might result in one of these arboviral diseases, people should wear long-sleeved shirts and pants while outside if feasible, apply insect repellant when going outdoors, using window screens or air conditioning to keep mosquitoes outside, and perform tick checks after being in wooded or brushy outdoor areas. PMID- 26903032 TI - Effects of forests, roads and mistletoe on bird diversity in monoculture rubber plantations. AB - Rising global demand for natural rubber is expanding monoculture rubber (Hevea brasilensis) at the expense of natural forests in the Old World tropics. Conversion of forests into rubber plantations has a devastating impact on biodiversity and we have yet to identify management strategies that can mitigate this. We determined the life-history traits that best predict bird species occurrence in rubber plantations in SW China and investigated the effects of surrounding forest cover and distance to roads on bird diversity. Mistletoes provide nectar and fruit resources in rubber so we examined mistletoe densities and the relationship with forest cover and rubber tree diameter. In rubber plantations, we recorded less than half of all bird species extant in the surrounding area. Birds with wider habitat breadths and low conservation value had a higher probability of occurrence. Species richness and diversity increased logarithmically with surrounding forest cover, but roads had little effect. Mistletoe density increased exponentially with rubber tree diameters, but was unrelated to forest cover. To maximize bird diversity in rubber-dominated landscapes it is therefore necessary to preserve as much forest as possible, construct roads through plantations and not forest, and retain some large rubber trees with mistletoes during crop rotations. PMID- 26903033 TI - Prosody and Semantics Are Separate but Not Separable Channels in the Perception of Emotional Speech: Test for Rating of Emotions in Speech. AB - PURPOSE: Our aim is to explore the complex interplay of prosody (tone of speech) and semantics (verbal content) in the perception of discrete emotions in speech. METHOD: We implement a novel tool, the Test for Rating of Emotions in Speech. Eighty native English speakers were presented with spoken sentences made of different combinations of 5 discrete emotions (anger, fear, happiness, sadness, and neutral) presented in prosody and semantics. Listeners were asked to rate the sentence as a whole, integrating both speech channels, or to focus on one channel only (prosody or semantics). RESULTS: We observed supremacy of congruency, failure of selective attention, and prosodic dominance. Supremacy of congruency means that a sentence that presents the same emotion in both speech channels was rated highest; failure of selective attention means that listeners were unable to selectively attend to one channel when instructed; and prosodic dominance means that prosodic information plays a larger role than semantics in processing emotional speech. CONCLUSIONS: Emotional prosody and semantics are separate but not separable channels, and it is difficult to perceive one without the influence of the other. Our findings indicate that the Test for Rating of Emotions in Speech can reveal specific aspects in the processing of emotional speech and may in the future prove useful for understanding emotion-processing deficits in individuals with pathologies. PMID- 26903035 TI - Contributions of North American endophytes to the phylogeny, ecology, and taxonomy of Xylariaceae (Sordariomycetes, Ascomycota). AB - The Xylariaceae (Sordariomycetes) comprise one of the largest and most diverse families of Ascomycota, with at least 85 accepted genera and ca. 1343 accepted species. In addition to their frequent occurrence as saprotrophs, members of the family often are found as endophytes in living tissues of phylogenetically diverse plants and lichens. Many of these endophytes remain sterile in culture, precluding identification based on morphological characters. Previous studies indicate that endophytes are highly diverse and represent many xylariaceous genera; however, phylogenetic analyses at the family level generally have not included endophytes, such that their contributions to understanding phylogenetic relationships of Xylariaceae are not well known. Here we use a multi-locus, cumulative supermatrix approach to integrate 92 putative species of fungi isolated from plants and lichens into a phylogenetic framework for Xylariaceae. Our collection spans 1933 isolates from living and senescent tissues in five biomes across the continental United States, and here is analyzed in the context of previously published sequence data from described species and additional taxon sampling of type specimens from culture collections. We found that the majority of strains obtained in our surveys can be classified in the hypoxyloid and xylaroid subfamilies, although many also were found outside of these lineages (as currently circumscribed). Many endophytes were placed in lineages previously not known for endophytism. Most endophytes appear to represent novel species, but inferences are limited by potential gaps in public databases. By linking our data, publicly available sequence data, and records of ascomata, we identify many geographically widespread, host-generalist clades capable of symbiotic associations with diverse photosynthetic partners. Concomitant with such cosmopolitan host use and distributions, many xylariaceous endophytes appear to inhabit both living and non-living plant tissues, with potentially important roles as saprotrophs. Overall, our study reveals major gaps in the availability of multi-locus datasets and metadata for this iconic family, and provides new hypotheses regarding the ecology and evolution of endophytism and other trophic modes across the family Xylariaceae. PMID- 26903036 TI - Chloroplast phylogenomic data from the green algal order Sphaeropleales (Chlorophyceae, Chlorophyta) reveal complex patterns of sequence evolution. AB - Chloroplast sequence data are widely used to infer phylogenies of plants and algae. With the increasing availability of complete chloroplast genome sequences, the opportunity arises to resolve ancient divergences that were heretofore problematic. On the flip side, properly analyzing large multi-gene data sets can be a major challenge, as these data may be riddled with systematic biases and conflicting signals. Our study contributes new data from nine complete and four fragmentary chloroplast genome sequences across the green algal order Sphaeropleales. Our phylogenetic analyses of a 56-gene data set show that analyzing these data on a nucleotide level yields a well-supported phylogeny - yet one that is quite different from a corresponding amino acid analysis. We offer some possible explanations for this conflict through a range of analyses of modified data sets. In addition, we characterize the newly sequenced genomes in terms of their structure and content, thereby further contributing to the knowledge of chloroplast genome evolution. PMID- 26903034 TI - Overexpression of GA20-OXIDASE1 impacts plant height, biomass allocation and saccharification efficiency in maize. AB - Increased biomass yield and quality are of great importance for the improvement of feedstock for the biorefinery. For the production of bioethanol, both stem biomass yield and the conversion efficiency of the polysaccharides in the cell wall to fermentable sugars are of relevance. Increasing the endogenous levels of gibberellic acid (GA) by ectopic expression of GA20-OXIDASE1 (GA20-OX1), the rate limiting step in GA biosynthesis, is known to affect cell division and cell expansion, resulting in larger plants and organs in several plant species. In this study, we examined biomass yield and quality traits of maize plants overexpressing GA20-OX1 (GA20-OX1). GA20-OX1 plants accumulated more vegetative biomass than control plants in greenhouse experiments, but not consistently over two years of field trials. The stems of these plants were longer but also more slender. Investigation of GA20-OX1 biomass quality using biochemical analyses showed the presence of more cellulose, lignin and cell wall residue. Cell wall analysis as well as expression analysis of lignin biosynthetic genes in developing stems revealed that cellulose and lignin were deposited earlier in development. Pretreatment of GA20-OX1 biomass with NaOH resulted in a higher saccharification efficiency per unit of dry weight, in agreement with the higher cellulose content. On the other hand, the cellulose-to-glucose conversion was slower upon HCl or hot-water pretreatment, presumably due to the higher lignin content. This study showed that biomass yield and quality traits can be interconnected, which is important for the development of future breeding strategies to improve lignocellulosic feedstock for bioethanol production. PMID- 26903037 TI - Correlation between the plasma fibrinogen concentration and coronary heart disease severity in Moroccan patients with type 2 diabetes. Prospective study. AB - AIM: The present study aims at determining the relationship between the plasma fibrinogen concentration and the severity of coronary heart disease in type 2 diabetic patients. METHODS: Prospective analytical survey, based on a sample of 120 subjects divided in four groups: 30 non diabetic coronary patients (G1), 30 coronary diabetic patients (G2), 30 non-coronary diabetic patients (G3), and 30 healthy subjects (G4). RESULTS: The average age was 59.58+/-7.88 years; female gender predominated by 52.5%. The plasma fibrinogen concentration corresponded to 3.46g/L+/-0.86 in G1; 3.73g/L+/-1.11 in G2; 3.06g/L+/-0.98 in G3 and 2.46g/L+/ 0.51 in G4; with a significant difference between the four groups (P=0.001). The plasma fibrinogen concentration increased in parallel with the cardiovascular risk (P=0.0001); there was also a significant correlation between the plasma fibrinogen concentration and the clinical and para-clinical coronary disease severity (respectively P=0.005 and P=0.0001). A positive correlation between the plasma fibrinogen concentration and hyperglycemia (P=0.035) was found in G4. But no correlation with the lipids parameters, except for the low density lipoproteins in G3 (P=0.035). CONCLUSION: In the Moroccan population, the plasma fibrinogen concentration was positively and significantly correlated with the coronary heart disease severity. PMID- 26903038 TI - Corrigendum: The Serum Profile of Hypercytokinemia Factors Identified in H7N9 Infected Patients can Predict Fatal Outcomes. PMID- 26903039 TI - Sex-Specific Differences at Presentation and Outcomes Among Patients Undergoing Transcatheter Aortic Valve Replacement: A Cohort Study. AB - BACKGROUND: Female sex is associated with poorer outcomes after surgical aortic valve replacement (SAVR). Data on sex-specific differences after transcatheter aortic valve replacement (TAVR) are conflicting. OBJECTIVE: To examine sex specific differences in patients undergoing TAVR in the PARTNER (Placement of Aortic Transcatheter Valves) trial. DESIGN: Secondary analysis of the randomized and nonrandomized portions of the PARTNER trial. (ClinicalTrials.gov: NCT00530894). SETTING: 25 hospitals in the United States, Canada, and Germany. PATIENTS: High-risk and inoperable patients (1220 women and 1339 men). INTERVENTION: TAVR. MEASUREMENTS: Demographic characteristics, cardiac and noncardiac comorbidities, mortality, stroke, rehospitalization, vascular complications, bleeding complications, and echocardiographic valve parameters. RESULTS: At baseline, women had lower rates of hyperlipidemia, diabetes, smoking, and renal disease but higher Society of Thoracic Surgeons Predicted Risk of Mortality scores (11.9% vs. 11.1%; P < 0.001). After TAVR, women had more vascular complications (17.3% vs. 10.0%; difference, 7.29 percentage points [95% CI, 4.63 to 9.95 percentage points]; P < 0.001) and major bleeding (10.5% vs. 7.7%; difference, 2.8 percentage points [CI, 0.57 to 5.04 percentage points]; P = 0.012) but less frequent moderate and severe paravalvular regurgitation (6.0% vs. 14.3%; difference, -8.3 percentage points [CI, -11.7 to -5.0 percentage points]; P < 0.001). At 30 days, the unadjusted all-cause mortality rate (6.5% vs. 5.9%; difference, 0.6 percentage point [CI, -1.29 to 2.45 percentage points]; P = 0.52) and stroke incidence (3.8% vs. 3.0%; difference, 0.8 percentage point [CI, -0.62 to 2.19 percentage points]; P = 0.28) were similar. At 1 year, all-cause mortality was significantly lower in women than in men (19.0% vs. 25.9%; hazard ratio, 0.72 [CI, 0.61 to 0.85]; P < 0.001). LIMITATION: Secondary analysis that included nonrandomized trial data. CONCLUSION: Despite a higher incidence of vascular and bleeding complications, women having TAVR had lower mortality than men at 1 year. Thus, sex-specific risk in TAVR is the opposite of that in SAVR, for which female sex has been shown to be independently associated with an adverse prognosis. PRIMARY FUNDING SOURCE: Edwards Lifesciences. PMID- 26903042 TI - Two-dimensional transition-metal oxide monolayers as cathode materials for Li and Na ion batteries. AB - Two-dimensional monolayers are attractive for applications in metal-ion batteries because of their low ion-diffusion barrier and volume expansion. In this work, we carry out a first-principles study on electrochemical and structural properties of two-dimensional (2D) oxide monolayers and investigate their applications in metal-ion batteries. 2D transition-metal oxide monolayers (MO2; M = Mn, Co, and Ni) with various ion-intercalation densities are systematically studied. Our calculations show that Li and Na atoms can easily be transported on the surfaces of the monolayers with low diffusion barriers because of the long binding distance. We find that Li2MO2 and Na2MO2 are stable because of negative intercalation energies and unsaturated specific energies. We show that MnO2 has the lowest diffusion barrier, highest specific capacity, and smallest lattice expansion under Li-intercalation, but lowest cell voltage. We also find that CoO2 shows the largest cell voltages in a wide range of ion-intercalation densities and smallest lattice expansion under Na-intercalation, and NiO2 only gives the highest cell voltage in Li2NiO2 and has the largest volume expansion. We further show that Li and Na atoms in Li2MO2 and Na2MO2 move from stable-adsorption sites to metastable sites on the surfaces of oxide monolayers to reduce lattice expansion, leading to reduced cell voltages. It is expected that metal-ion batteries with particular applications and performances can be achieved in the design of these oxide monolayers. PMID- 26903041 TI - Anthropogenic disturbances are key to maintaining the biodiversity of grasslands. AB - Although anthropogenic disturbances are often perceived as detrimental to plant biodiversity, the relationship between biodiversity and disturbance remains unclear. Opinions diverge on how natural diversity is generated and maintained. We conducted a large-scale investigation of a temperate grassland system in Inner Mongolia and assessed the richness-disturbance relationship using grazing intensity, the primary anthropogenic disturbance in the region. Vascular plant species richness peaked at an intermediate level of anthropogenic disturbance. Our results support the Intermediate Disturbance Hypothesis, which provides a valid and useful measure of biodiversity at a metacommunity scale, indicating that anthropogenic disturbances are necessary to conserve the biodiversity of grassland systems. PMID- 26903044 TI - Intraoperative Radiation Therapy in Breast Cancer: Still Not Ready for Prime Time. PMID- 26903045 TI - Nomograms for Pre-operative and Post-operative Prediction of Long-Term Survival of Patients Who Underwent Repeat Hepatectomy for Recurrent Hepatocellular Carcinoma. AB - BACKGROUND: Repeat hepatectomy (re-hepatectomy) is an effective treatment for patients with intrahepatic recurrence following liver resection for hepatocellular carcinoma (HCC). OBJECTIVE: This study aimed to develop nomograms for predicting prognosis after re-hepatectomy. METHODS: The data of 635 patients who underwent re-hepatectomy for recurrent HCC at the Eastern Hepatobiliary Surgery Hospital between 2004 and 2010 were prospectively collected. Multivariable Cox regression analyses based on data obtained before and after re hepatectomy were performed to select independent predictors of recurrence to death survival (RTDS) which were incorporated into the pre- or post-re hepatectomy nomograms. Discrimination and calibration of the nomograms were measured using the concordance index (C-index), Kaplan-Meier curves, and calibration plots. RESULTS: The 1-, 3- and 5-year overall survival rates were 96.9, 74.8, and 47.8 %, respectively, and the corresponding RTDS rates were 75.8, 45.7, and 37.6 %, respectively. Tumor size and number at the initial and recurrent stages, time to recurrence from the initial hepatectomy, hepatitis B virus deoxyribonucleic acid level and microvascular invasion were selected into the two nomograms. The C-indexes for predicting RTDS were 0.72 [95 % confidence interval (CI) 0.70-0.74] and 0.77 (95 % CI 0.74-0.80) for the pre- or post-re hepatectomy nomograms, respectively. The calibration curves for the probability of 5-year RTDS after re-hepatectomy showed optimal agreement between the prediction shown in the nomograms and the actual observations. Both nomograms were able to accurately stratify patients into four distinct incremental prognostic subgroups. CONCLUSION: The proposed nomograms have shown accurate RTDS prediction for patients with intrahepatic recurrent HCC. PMID- 26903046 TI - Erratum to: Oncoplastic Breast-Conserving Surgery for Tumors Larger than 2 Centimeters: Is it Oncologically Safe? A Matched-Cohort Analysis. PMID- 26903047 TI - Transthoracic Port Placement Increases Safety of Total Laparoscopic Posterior Sectionectomy. AB - BACKGROUND: Anatomic posterior sectionectomy is performed infrequently due to the challenges of controlling the right posterior portal pedicle (RPPP) while preserving the anterior pedicle (RAPP), difficulty of visualizing the drainage of the right hepatic vein into the IVC, and the potential for significant blood loss during the caval and hepatovenous dissection. PATIENT: A 62-year-old woman with three liver metastases to SVI and SVII from sigmoid colon cancer underwent five cycles of neoadjuvant chemotherapy with FOLFOX and bevacizumab with good response. She underwent a "Primary First" robotic low anterior rectosigmoid resection followed by a laparoscopic posterior sectionectomy. TECHNIQUE: The patient was placed in a Modified French Position. As previously described, a transthoracic trocar was placed for optimal laparoscopic visualization and access of the superior retrohepatic IVC and drainage of the right hepatic vein into IVC. Intraoperative ultrasound was crucial to assess tumor location, define transection plane, and preserve flow to RAPP before division of RPPP. The parenchymal transection follows an oblique angle and exposes the right hepatic vein. CONCLUSIONS: Transthoracic port placement augments the safety of the dissection along the IVC inferiorly and the right hepatic vein superiorly due to direct visualization. Also, it provides a direct instrument-to-target axis without the typical fulcrum of dissecting the postero/superior liver. Laparoscopic ultrasound is critical to confirm preserved flow to the RPPP and guide the parenchymal transection. Liver volumetry should be obtained before surgery to determine adequate future liver remnant if conversion to a right lobectomy becomes necessary. PMID- 26903048 TI - Increased Salinization Decreases Safe Drinking Water. PMID- 26903050 TI - Lumbar microendoscopic discectomy: surgical technique and nuances. AB - BACKGROUND: Lumbar microendoscopic discectomy (MED) is a minimally invasive transmuscular approach that combines standard lumbar microsurgical techniques with endoscopy. MED advantages include reduced tissue trauma, direct visualization of the nerve root and disc disease, and allowing bony decompression in cases with spinal or lateral recess stenosis. METHODS: Operative charts and videos of patients undergoing MED were retrieved from our database and reviewed. A description of the surgical technique was then formulated. CONCLUSIONS: The surgical technique of MED is described and is essentially similar to conventional microdiscectomy. Some modifications are, however, necessary owing to the difference between microscopic and endoscopic views. PMID- 26903049 TI - Food sources of dietary sodium in the Japanese adult population: the international study of macro-/micronutrients and blood pressure (INTERMAP). AB - PURPOSE: It is often reported that Na intake levels are higher in Japan than in western countries. Detailed analysis of food intake and its association with Na intake are necessary for supporting further decreases in Na consumption in Japan. We investigated the association between Na and food intake by food group using data from the Japanese participants of the INTERMAP Study. METHOD: Results from the Japanese participants of the INTERMAP Study who did not use antihypertensive medication and/or consume a reduced Na diet were used (531 men and 518 women, aged 40-59 years), obtained from four 24-h dietary recalls and two 24-h urine collections from each participant. We developed a classification system with 46 food group classifications; food consumption and Na intake from these groups were compared across quartiles of participants determined by 24-h urinary Na excretion per unit of body weight (UNa/BW). RESULTS: Average daily Na intake from Japanese high-Na foods was 2552 mg/day. Participants with a higher UNa/BW consumed a significantly greater amount of high-Na Japanese foods, such as salted fish (P = 0.001) and miso soup (P < 0.001). They also had greater amount of rice (P = 0.001). Participants with lower UNa/BW consumed a significantly greater amount of western foods, such as bread (P < 0.001) and milk and dairy products (P < 0.001). CONCLUSIONS: Detailed analyses of various Japanese and western food intakes in addition to Na intake were performed. These results can be used to help draw up effective programs for the reduction in Na intake and prevention of prehypertension/hypertension in the Japanese population. PMID- 26903051 TI - Lomustine Nanoparticles Enable Both Bone Marrow Sparing and High Brain Drug Levels - A Strategy for Brain Cancer Treatments. AB - PURPOSE: The blood brain barrier compromises glioblastoma chemotherapy. However high blood concentrations of lipophilic, alkylating drugs result in brain uptake, but cause myelosuppression. We hypothesised that nanoparticles could achieve therapeutic brain concentrations without dose-limiting myelosuppression. METHODS: Mice were dosed with either intravenous lomustine Molecular Envelope Technology (MET) nanoparticles (13 mg kg(-1)) or ethanolic lomustine (6.5 mg kg(-1)) and tissues analysed. Efficacy was assessed in an orthotopic U-87 MG glioblastoma model, following intravenous MET lomustine (daily 13 mg kg(-1)) or ethanolic lomustine (daily 1.2 mg kg(-1) - the highest repeated dose possible). Myelosuppression and MET particle macrophage uptake were also investigated. RESULTS: The MET formulation resulted in modest brain targeting (brain/ bone AUC0 4h ratios for MET and ethanolic lomustine = 0.90 and 0.53 respectively and brain/ liver AUC0-4h ratios for MET and ethanolic lomustine = 0.24 and 0.15 respectively). The MET formulation significantly increased mice (U-87 MG tumours) survival times; with MET lomustine, ethanolic lomustine and untreated mean survival times of 33.2, 22.5 and 21.3 days respectively and there were no material treatment-related differences in blood and femoral cell counts. Macrophage uptake is slower for MET nanoparticles than for liposomes. CONCLUSIONS: Particulate drug formulations improved brain tumour therapy without major bone marrow toxicity. PMID- 26903053 TI - [A 5-year retrospective clinical study of perinatal cytomegalovirus infection]. AB - OBJECTIVE: To investigate the incidence, clinical features, and treatment of perinatal cytomegalovirus (CMV) infection, as well as the factors affecting the therapeutic effect of ganciclovir. METHODS: The clinical data of 237 infants who were hospitalized and diagnosed with perinatal CMV infection from 2008 to 2012 were retrospectively analyzed. RESULTS: The clinical features of infants with perinatal CMV infection and the proportion of such infants in all hospitalized infants showed no significant differences across the five years. In most infants, two or more systems were involved, and CMV hepatitis plus CMV pneumonia was most common (43.1%). The results of pathogen detection showed that the percentage of the infants with positive blood CMV-IgM and blood/urine CMV-DNA was 3.8%, while 90.3% of all infants had positive blood CMV-IgM alone and 5.9% had positive blood/urine CMV-DNA alone. A total of 197 infants were treated with ganciclovir, and the cure rate was 88.3%. An abnormal history of pregnancy (OR=6.191, 95% CI: 1.597-24.002) and liver involvement before medication (OR=3.705, 95% CI: 1.537 8.931) were the independent risk factors affecting the therapeutic effect of ganciclovir in infants with perinatal CMV infection. CONCLUSIONS: The epidemiological characteristics of perinatal CMV infection have remained generally stable for the last 5 years. CMV often involves several organs or systems, especially the liver and lung. Ganciclovir has a significant efficacy in the treatment of perinatal CMV infection, and an abnormal history of pregnancy and liver involvement before medication can increase the risk of ganciclovir resistance in infants with perinatal CMV infection. PMID- 26903052 TI - Renin-angiotensin system inhibitors and fibrosis in chronic liver disease: a systematic review. AB - BACKGROUND AND AIMS: The renin-angiotensin system (RAS) has an important role in hepatic fibrosis and portal hypertension. RAS inhibitors are already accepted in clinical fields for antihypertensive management, but their effects on hepatic fibrosis are controversial. The aim of this study was to systematically review the effects of RAS inhibitors on hepatic fibrosis based on histological assessment. METHODS: We performed a systematic review and meta-analysis (MA) of the literature using the Ovid-MEDLINE, EMBASE, and Cochrane Library databases (up to January 2015) to identify clinical studies evaluating the effects of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers on hepatic fibrosis or cirrhosis patients based on histological assessment. Of the 455 studies identified, we analyzed 7, including a total of 1066 patients, which met our selection criteria. RESULTS: According to the MA, patients treated with RAS inhibitors had significantly lower fibrosis scores (SMD -0.68, 95 % CI -1.03, -0.34, I (2) = 0 %, p < 0.0001) and smaller fibrosis areas (SMD -0.80, 95 % CI 1.18, -0.41, I (2) = 0 %, p < 0.0001) than controls. Serum fibrosis markers such as TGF-beta1, collagen I, IV, TIMP-1, and MMP2 were significantly reduced in the intervention group. In two studies, mean arterial pressures were significantly decreased in RAS inhibitor users, but there were no reports about symptoms related to decreased blood pressure. No significant difference was found in serum creatinine levels between the intervention and control groups, and significant renal dysfunction was not observed after administration of RAS inhibitors. CONCLUSIONS: RAS inhibitors are potential therapeutic agents for hepatic fibrosis, which can be safely used in patients with chronic liver disease. PMID- 26903054 TI - [Diagnostic value of prealbumin for severe necrotizing enterocolitis]. AB - OBJECTIVE: To study the clinical features of severe neonatal necrotizing enterocolitis (NEC), and to investigate the diagnostic value of prealbumin (PA) in neonates with severe NEC. METHODS: The clinical data and results of routine blood test and blood biochemical test of 40 neonates with NEC (29 neonates with NEC II and 11 with NEC III) were analyzed. The multivariate logistic regression analysis and receiver operating characteristic (ROC) curve were applied to investigate the value of PA in the diagnosis of severe NEC. RESULTS: The multivariate logistic regression analysis showed that PA was an important index for the diagnosis of severe NEC (≥IIB). The ROC analysis showed that in the diagnosis of severe NEC (≥IIB), PA had high sensitivity (0.870) and specificity (0.647). CONCLUSIONS: PA has a good value in the diagnosis of severe NEC. PMID- 26903055 TI - [Value of abdominal ultrasound in the diagnosis of neonatal necrotizing enterocolitis and evaluation of disease severity]. AB - OBJECTIVE: To investigate the value of abdominal ultrasound in diagnosing neonatal necrotizing enterocolitis (NEC) and its significance in evaluating the disease severity. METHODS: The clinical data of 84 neonates who were diagnosed with NEC between July 2013 and January 2015 were analyzed retrospectively. According to the modified Bell-NEC staging criteria, these neonates were divided into a suspected NEC group (n=44) and a confirmed NEC group (n=40); according to clinical prognosis, they were divided into a medical treatment and full recovery group (n=58) and a surgery/death group (n=26). The changes in the results of abdominal ultrasound and abdominal X-ray plain film were compared between groups. RESULTS: In the confirmed NEC group, abdominal ultrasound showed significantly higher detection rates of portal venous gas and dilatation of the intestine than abdominal X-ray plain film (P<0.05). Compared with the medical treatment and full recovery group, the surgery/death group had significantly higher detection rates of dilatation of intestine, bowel wall thickening, peritoneal effusion and free intraperitoneal air (P<0.05). Dilatation of the intestine and free intraperitoneal air shown by abdominal X-ray plain film were more common in the surgery/death group. CONCLUSIONS: Abdominal ultrasound is useful for the diagnosis of NEC. Ultrasonic findings can contribute to the prediction of the severity of NEC. PMID- 26903056 TI - [Changes in gut microbiota and serum D-lactate level and correlation analysis in children with recurrent pneumonia]. AB - OBJECTIVE: To study the changes in gut microbiota and serum D-lactate level and their significance in children with recurrent pneumonia. METHODS: The stool and blood samples were collected from 30 children with recurrent pneumonia (recurrent group), 30 children with acute pneumonia (acute group), and 15 children receiving surgical operation (surgery group). The 16S rRNA fluorescent quantitative polymerase chain reaction (FQ-PCR) was applied to determine the numbers of Bifidobacterium and Escherichia coli in stool samples, and the ratio between the logarithmic values of the numbers of Bifidobacterium and Escherichia coli (B/E value) was calculated. The serum D-lactate level was measured, and correlation analysis was performed. RESULTS: The recurrent group had a significantly lower number of Bifidobacterium and a significantly lower B/E value than the acute group and the surgery group (P<0.05), as well as a significantly higher number of Escherichia coli than the surgery group (P<0.05). There was no significant difference in the number of Escherichia coli between the recurrent group and the acute group. The recurrent group had a significantly higher serum D-lactate level than the acute group and the surgery group (P<0.05). In the recurrent group, B/E value was negatively correlated with serum D-lactate level (r=-0.539, P<0.05). CONCLUSIONS: Children with recurrent pneumonia may have biological and mechanical barrier damage in the intestinal mucosa. PMID- 26903057 TI - [Lower respiratory tract infection caused by influenza virus A and influenza virus B in Wenzhou, China: a clinical analysis of 366 children]. AB - OBJECTIVE: To compare the epidemiological and clinical features of lower respiratory tract infection (LRTI) caused by influenza virus A (IVA) and influenza virus B (IVB) in children. METHODS: The clinical data of 366 children with LRTI caused by influenza virus (IV), who were hospitalized in Yuying Children′s Hospital of Wenzhou Medical University between 2010 and 2014, were analyzed retrospectively, and there were 272 cases caused by IVA and 94 cases caused by IVB. RESULTS: IV was mainly prevalent from December to March of the next year, with the predominance of IVA. There were small peaks of IVA prevalence in July or September every other year, and IVB was prevalent from December to March of the next year every other year. The children with LRTI caused by IVA alone had a significantly higher white blood cell (WBC) count and significantly higher percentages of children with increased WBC, abnormal serum sodium, and abnormal serum potassium than those caused by IVB alone (P<0.05). However, there were no significant differences in age, sex, underlying diseases, clinical manifestations, and co-infection rate with bacteria or atypical pathogens between the two groups (P>0.05). The rate of co-infection with respiratory syncytial virus (RSV) was significantly higher in the IVB group than in the IVA group (P<0.01). CONCLUSIONS: IVA is prevalent in winter and spring every year and has small peaks in summer every other year, while IVB is prevalent in winter and spring every other year. Compared with IVB, IVA causes more cases of increased WBC and electrolyte disturbance. The children infected with IVB are more likely to be co-infected with RSV. The children with LRTI caused by IVA and IVB have similar clinical manifestations. PMID- 26903058 TI - [Effect of botulinum toxin A injection in the treatment of gastrocnemius spasticity in children aged 9-36 months with cerebral palsy: a prospective study]. AB - OBJECTIVE: To investigate the long-term clinical efficacy and adverse effects of botulinum toxin-A (BTX-A) injection in the treatment of gastrocnemius spasticity in children aged 9-36 months with cerebral palsy. METHODS: Eighty children aged 9 36 months with cerebral palsy and gastrocnemius spasticity were selected and randomly divided into a BTX-A injection group and a conventional treatment group (n=40 each). The children in the BTX-A injection group received injections of BTX A guided by color Doppler ultrasound and 4 courses of rehabilitation training after injection. Those in the conventional treatment group received 4 courses of the same rehabilitation training alone. Before treatment and at 1, 2, 3, and 6 months after treatment, the modified Tardieu scale (MTS) was applied to assess the degree of gastrocnemius spasticity, the values in the passive state measured by surface electromyography (sEMG) were applied to evaluate muscle tension, and the Gross Motor Function Measure (GMFM) was used to evaluate gross motor function. RESULTS: Compared with the conventional treatment group, the BTX-A injection group had significantly greater reductions in MTS score and the values in the passive state measured by sEMG (P<0.05), as well as significantly greater increases in joint angles R1 and R2 in MTS and gross motor score in GMFM (P<0.05). No serious adverse reactions related to BTX-A injection were found. CONCLUSIONS: BTX-A injection is effective and safe in the treatment of gastrocnemius spasticity in children aged 9-36 months with cerebral palsy. PMID- 26903059 TI - [Comparison of therapeutic effects of prednisone combined with mycophenolate mofetil versus cyclosporin A in children with steroid-resistant nephrotic syndrome]. AB - OBJECTIVE: To compare the therapeutic effects of prednisone combined with mycophenolate mofetil (MMF) versus cyclosporin A (CsA) in children with steroid resistant nephrotic syndrome (SRNS). METHODS: The clinical data of 164 SRNS children who were treated with prednisone combined with MMF or CsA between January 2004 and December 2013 were collected, and the clinical effect of prednisone combined with MMF (MMF group, 112 children) or CsA (CsA group, 52 children) was analyzed retrospectively. RESULTS: At 1 month after treatment, the CsA group had a significantly higher remission rate than the MMF group (67.3% vs 42.9%; P<0.05). At 3 months after treatment, the CsA group also had a significantly higher remission rate than the MMF group (78.8% vs 63.3%; P<0.05). The 24-hour urinary protein excretion in both groups changed significantly with time (P<0.05) and differed significantly between the two groups (P<0.05). There were no serious adverse events in the two groups. CONCLUSIONS: Prednisone combined with MMF or CsA is effective and safe for the treatment of SRNS in children, and within 3 months of treatment, CsA has a better effect than MMF. PMID- 26903060 TI - [Change in serum follistatin-like protein 1 and its clinical significance in children with chronic heart failure]. AB - OBJECTIVE: To investigate the change in the serum level of follistatin-like protein 1 (FSTL1) in children with chronic heart failure and its correlation with left ventricular remodeling. METHODS: A total of 45 children with chronic heart failure (CHF) between May 2014 and May 2015 were selected as the CHF group, among whom 21 had endocardial fibroelastosis (EFE) and 24 had dilated cardiomyopathy (DCM); another 30 healthy children were selected as the control group. Enzyme linked immunosorbent assay was applied to measure the serum level of FSTL1. Radioimmunoassay was applied to measure N-terminal pro-brain natriuretic peptide, and echocardiography was applied to measure the indicators of left ventricular remodeling. The correlation between the serum level of FSTL1 and left ventricular remodeling was analyzed by Pearson correlation and Spearman′s rank correlation analysis. RESULTS: Before treatment, the CHF group had a significantly higher serum level of FSTL1 than the control group (P<0.05), which gradually increased with aggravation of CHF (P<0.05). The serum level of FSTL1 showed no significant difference between the EFE and DCM groups (P=0.176). Serum level of FSTL1 was positively correlated with left ventricular end-diastolic diameter (r=0.485, P=0.001), left ventricular mass (r=0.322, P=0.031), left ventricular mass index (r=0.353, P=0.017), and N-terminal pro-brain natriuretic peptide (r=0.562 P<0.001), and was negatively correlated with left ventricular ejection fraction (r=-0.436, P=0.003) and left ventricular minor axis decurtation rate (r=-0.436, P=0.003). CONCLUSIONS: FSTL1 might take part in the left ventricular remodeling in children with CHF, and the serum level of FSTL1 can be used as an objective index for clinical diagnosis and severity assessment of CHF in children. PMID- 26903061 TI - [Genotypes and phenotypes in Uygur children with 21-hydroxylase deficiency in Xinjiang, China]. AB - OBJECTIVE: To investigate gene mutations and the relationship between genotypes and clinical phenotypes in Uygur children with 21-hydroxylase deficiency (21-OHD) in Xinjiang, China. METHODS: A total of 20 Uygur children with 21-OHD who visited the hospital between October 2013 and October 2014 were enrolled. Full-length direct sequencing and multiplex ligation-dependent probe amplification (MLPA) were used to detect the mutations of CYP21A2 gene, which encoded 21-hydroxylase. According to the type of mutation, the patients with 21-OHD were divided into different groups to analyze the consistency between predicted clinical phenotypes and actual clinical phenotypes. RESULTS: A total of 9 mutation types were found in the 20 patients, and 8 of them were identified as pathogenic mutations, i.e., Del, conv, I2g, I172N, Cluster E6, 8-bp del, V281L, and R356W. The other mutation is the new mutation occurring in intron 5 (c.648+37A>G), which had not been reported, and its pathological significance remains unknown. Most clinical phenotypes predicted by mutation types had a higher coincidence rate with actual clinical phenotypes (above 67%), and the clinical phenotypes predicted by P30L and V281L had a lower coincidence rate with actual clinical phenotypes (below 33%). CONCLUSIONS: The genotype of 21-OHD has a good correlation with phenotype, and the clinical phenotype can be predicted by detecting the patient′s genotype. The new mutation (c.648+37A>G) may be related to the pathogenesis of 21 OHD. PMID- 26903062 TI - [Clinical analysis and autoimmune regulator gene mutation of autoimmune polyendocrinopathy syndrome type I in a family: a report of one case]. AB - The clinical data of one patient with autoimmune polyendocrinopathy syndrome type I were collected. PCR-DNA direct bidirectional sequencing was applied for mutation screening of 14 exons in autoimmune regulator (AIRE) gene in the patient and her parents. A total of 50 unrelated healthy controls were selected and tested. The bioinformatic methods were used to predict the possible impact of the mutations on the structure and function of the AIRE protein. The results of sequencing showed that heterozygous mutation c.622G>T (p.G208W) in exon 5 of the AIRE gene was detected in the patient and was a novel mutation, which had not been reported in the HGMD database and latest articles. This mutation was not detected in the 50 unrelated normal controls. The novel mutation of c.622G>T (p.G208W) in AIRE gene might play an important role in the pathogenesis of this case of autoimmune polyendocrinopathy syndrome type I. PMID- 26903064 TI - [Correlation between uncoupling protein 2 expression and myocardial mitochondrial injury in rats with sepsis induced by lipopolysaccharide]. AB - OBJECTIVE: To investigate the correlation between uncoupling protein 2 (UCP2) expression and myocardial mitochondria injury in rats with sepsis induced by lipopolysaccharide (LPS). METHODS: The rat model of sepsis was established through an intraperitoneal injection of LPS. Forty male Sprague-Dawley rats were randomly and equally divided into control group (an intraperitoneal injection of normal saline), sepsis 6 h group (LPS-6 h group), sepsis 12 h group (LPS-12 h group), sepsis 24 h group (LPS-24 h group), and sepsis 48 h group (LPS-48 h group). The serum and heart tissues were harvested at corresponding time points and myocardial mitochondria was extracted. The microplate reader was applied to measure creatine kinase (CK), creatine kinase-MB (CK-MB), and reactive oxygen species (ROS). Flow cytometry was applied to measure the degree of mitochondrial swelling and mitochondrial membrane potential (MMP). Western blot was used to measure the expression level of UCP2. Electron microscopy was applied to observe the morphological changes in heart tissues and myocardial mitochondria. RESULTS: Compared with the control group, the LPS groups had significantly increased serum levels of CK, CK-MB, and myocardial ROS, as well as a significantly increased degree of mitochondrial swelling (P<0.05), and these values reached their peaks at 24 hours after LPS injection. The LPS groups had a significant decrease in MMP (P<0.05), which reached the lowest level at 24 hours after LPS injection. Western blot showed that the LPS groups had a significant increase in the expression level of myocardial UCP2 compared with the control group (P<0.05), which reached its peak at 24 hours after LPS injection. The results of electron microscopy showed mitochondrial swelling, partial rupture of the mitochondrial membrane, and cavity formation in rats in the LPS groups. The most severe lesions occurred in the LPS-24 h group. In rats with LPS, the ROS level in the myocardial mitochondria and the degree of mitochondrial swelling were positively correlated with the expression level of UCP2 (r=0.796 and 0.893, respectively; P<0.05), while MMP was negatively correlated with the expression level of UCP2 (r=-0.903, P<0.05). CONCLUSIONS: In the rat model of sepsis, the myocardium and myocardial mitochondria have obvious injuries, and the expression level of UCP2 is closely correlated with mitochondrial injury. Therefore, UCP2 might play an important role in myocardial mitochondrial injury in sepsis. PMID- 26903063 TI - [Effect of heat shock protein 70 on pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension]. AB - OBJECTIVE: To investigate the effect of heat shock protein 70 (HSP70) on pulmonary arterial pressure and pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension (HPH). METHODS: A total of 128 Wistar neonatal rats were randomly divided into HPH model and blank control groups. According to the transfection solution, the HPH model group was further divided into normal saline group, empty virus group (viral vectors marked with a green fluorescent signal and not carrying the target gene), and virus+HSP70 group (viral vectors marked with a green fluorescent signal and carrying the target gene). The HPH model was established by inhalation of nitrogen-oxygen mixture (1.5 L/minutes and 8% oxygen). Pulmonary arterial pressure (mPAP) and the indicators of pulmonary vascular remodeling (MT% and MA%) were measured on days 3, 7, 10, and 14 of hypoxia. RESULTS: On days 3, 7, and 10 of hypoxia, the normal saline and empty virus groups had significantly enhanced expression of HSP70 compared with the blank control group (P<0.01), and the virus+HSP70 group had significantly higher expression of HSP70 than the blank control, normal saline, and empty virus groups (P<0.01). On day 14 of hypoxia, the expression of HSP70 showed no significant difference between these groups (P>0.05). On days 3, 7, and 10 of hypoxia, the normal saline and empty virus groups showed continuous increases in mPAP compared with the blank control group (P<0.05). There was no significant difference in mPAP between the virus+HSP70 and blank control groups (P>0.05). On day 14 of hypoxia, there was no significant difference in mPAP among three subgroups of the HPH model group (P>0.05), but the mPAP in the three subgroups was significantly higher than in the blank control group (P<0.05). After 7 days of hypoxia, the normal saline and empty virus groups showed significantly higher MT% and MA% than the blank control group (P<0.05), but the two indicators showed no significant differences between the virus+HSP70 and the blank control groups (P>0.05). On day 14 of hypoxia, there were no significant differences in MT% and MA% among three subgroups of the HPH model group (P>0.05), but the MT% and MA% in the three subgroups were higher than in the blank control group (P<0.05). CONCLUSIONS: HSP70 may reduce pulmonary arterial pressure and pulmonary vascular remodeling in neonatal rats with HPH. PMID- 26903065 TI - [Protective effect of emodin pretreatment in young rats with intrahepatic cholestasis]. AB - OBJECTIVE: To investigate the protective effect of emodin in young rats with intrahepatic cholestasis. METHODS: A total of 120 young Sprague-Dawley rats were randomly divided into control, model, and high-, medium-, and low-dose emodin groups, with 24 rats in each group. The rats in the control and model groups were given sodium carboxymethyl cellulose solution by gavage, while the other groups were given different doses of emodin solution by gavage. On the 5th day of experiment, alpha-naphthylisothiocyanate (ANIT, 50 mg/kg) was applied by gavage to establish the model of intrahepatic cholestasis in all groups except the control group. At 24, 48, and 72 hours after gavage, 8 rats in each group were sacrificed. Colorimetry was used to measure the serum levels of total bilirubin (TBIL), direct bilirubin (DBIL), total bile acid (TBA), alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in each group, and hematoxylin-eosin staining was applied to observe the morphological changes of the liver under a light microscope at different time points. RESULTS: Compared with the control group, the model group had significantly increased serum levels of TBIL, DBIL, TBA, ALP, GGT, ALT, and AST at the 24-hour, 48-hour, and 72-hour time points (P<0.01). In the model group, the serum levels of TBIL, DBIL, TBA, ALT, and AST showed varying degrees of increase at 48 hours after establishment of model, compared with the values at 24 and 72 hours (P<0.05). At 24, 48, and 72 hours, the high-, medium-, and low-dose emodin groups had varying degrees of reductions in the serum levels of TBIL and TBA compared with the model group (P<0.05); the high- and low-dose emodin groups had significantly increased serum levels of TBA compared with the medium-dose emodin group (P<0.05). The model group had the most severe pathological changes at 48 hours. Compared with the model group, the high-, medium-, and low-dose emodin groups showed certain improvement in pathological changes of the liver at each time point, and the medium-dose emodin group had better improvement compared with the high- and low-dose emodin groups. CONCLUSIONS: Emodin can effectively improve ANIT-induced intrahepatic cholestasis in young rats, and medium-dose emodin shows the best effect. PMID- 26903067 TI - [Vitamin A level and diseases of premature infants]. AB - Vitamin A is a fat-soluble vitamin, and it is not only necessary for the normal growth and development of epithelial cells, but also plays a very important role in the normal growth and development of the retina, lungs, gastrointestinal tract, brain, and immune system. Studies have confirmed that the low level of vitamin A in premature infants at birth can last through the entire infancy. Recently, there have been particular concerns about the level of vitamin A and development of diseases in premature infants, with major focuses on the related mechanisms of action of vitamin A in respiratory distress syndrome, chronic lung disease, retinopathy of prematurity, necrotizing enterocolitis, patent ductus arteriosus, and infections in premature infants, which still awaits further investigation.This paper summarizes and analyzes the current status of research on vitamin A level and diseases of premature infants at home and abroad. In addition, although enough evidence suggests that vitamin A supplementation is beneficial to preterm infants, evidence is still lacking for recommended methods for supplementation and dose of vitamin A, and further studies are needed. PMID- 26903066 TI - [Expression and role of Tc17 cells in mice with neutrophilic asthma]. AB - OBJECTIVE: To determine the proportion of Tc17 cells in the lungs of mice with neutrophilic(NEU) asthma, and to investigate the role of Tc17 cells in the pathogenesis of NEU asthma. METHODS: Thirty-two C57/B6 mice of clean grade were randomly divided into two groups: NEU asthma and control. The mice in the NEU asthma group were sensitized by airway instillation of ovalbumin (OVA) and lipopolysaccharide (LPS), and challenged with an aerosol of OVA, while those in the control group were sensitized and challenged with normal saline. At 24 hours after the final challenge, bronchoalveolar lavage fluid (BALF) was collected, and the total number and differential counts of nucleated cells and percentage of each type were determined. The lung tissues were separated and hematoxylin-eosin staining was performed to observe the pathological changes of lungs; flow cytometry was applied to determine the percentages of Tc17 and Th17 cells in the lung tissues. Enzyme-linked immunosorbent assay was applied to determine the levels of interleukin-6 (IL-6), transforming growth factor β (TGF-β), and interleukin-17 (IL-17) in BALF. RESULTS: The NEU asthma group had a significantly higher total number of nucleated cells, a significantly higher percentage of eosinophils, and a significantly higher percentage of neutrophils in BALF than the control group (P<0.01). The NEU asthma group also had significantly higher percentages of Tc17 and Th17 cells than the control group (P<0.01). In the NEU asthma group, the percentage of Tc17 cells was positively correlated with that of Th17 cells (P<0.05). The NEU asthma group had significantly higher concentrations of IL-6, TGF-β, and IL-17 in BALF than the control group (P<0.05). CONCLUSIONS: The expression of Tc17 cells in the lung tissues increases in mice with NEU asthma, and the increased number of Tc17 cells may be involved in the pathogenesis of NEU asthma. Tc17 cells may play an important role in NEU asthma through IL-17. PMID- 26903068 TI - [Research advances in the role of vitamin D in autism spectrum disorders]. AB - The etiology and pathogenic mechanism of autism spectrum disorders (ASD) are still unclear. The relationship between vitamin D and ASD has drawn attention in recent years due to common vitamin D deficiency in children with ASD. This article reviews the peripheral blood levels of vitamin D in children with ASD, the possible reasons for hypovitamin D and its possible roles in the etiology of ASD and the efficacy of vitamin D supplementation in ASD. PMID- 26903069 TI - [Effect of probiotics in prevention and treatment of allergic diseases in children]. AB - The increasing incidence rate of allergic diseases has attracted global attention, and these diseases greatly threaten children′s health. The common pathogenesis of allergic diseases is the specific IgE- or cell-mediated immune response to common inhalant or food allergens. Epidemiological investigation, analysis of fecal flora, and clinical studies all suggest that the development and progression of allergic diseases are closely related to the early disturbance of intestinal flora. Probiotics can regulate intestinal immune response, increase the barrier function of epithelial cells, inhibit the adhesion and colonization of pathogenic bacteria, and thus restore or reconstruct normal intestinal flora. With the increasing understanding of allergic diseases, the effect of probiotics in the prevention and treatment of such diseases will be taken more and more seriously. PMID- 26903070 TI - Unrecorded Alcohol and Alcohol-Related Harm in Rural Sabah, Malaysia: A Socio economically Deprived Region with Expensive Beer and Cheap Local Spirits. AB - AIM: To investigate recorded and unrecorded alcohol and the relation to alcohol related harm in a region with high taxation, economic deprivation and cultural use of alcohol. METHODS: Two participants per household were systematically sampled from 12 different villages chosen using stratified random sampling in the North of Sabah, Malaysia. Participants were asked about each type and amount of drink consumed; price paid, whether tax was paid, number of days sick in the last year and whether they had experienced various health problems. A brief screen for mental disorders (PHQ) and an alcohol disorder screening test (AUDIT) were completed. Village heads were also interviewed about alcohol-related problems at village level. RESULTS: 470 people were interviewed. The most commonly drunk beverages were beer and Montoku (a local distilled beverage), which had average prices of RM3.85 and RM0.48 per standard drink respectively. Montoku was more likely to be drunk by problem drinkers. Only 3.1% of alcohol drunk was believed by respondents to be taxed. Men with an AUDIT score of more than 15 were more likely to have had a sick day in the last year and have a female household member with symptoms of mental disorder on PHQ. CONCLUSIONS: Change in the taxation structure needs to be considered to reduce alcohol-related harm. Most alcohol consumed in rural Sabah is smuggled or informal. The low price of local spirits is likely to be contributing to alcohol-related harm. Differential effects on minority populations need to be considered when designing alcohol policy. PMID- 26903071 TI - Natural Killer Cell-Based Immunotherapy in Acute Myeloid Leukemia: Lessons for the Future. AB - The article by Curti and colleagues highlights the potential of natural killer (NK) cell-based adoptive cellular immunotherapy in oncology, currently boosted by advances in the knowledge on NK cell biology and in theirex vivoGMP manipulation. Several issues deserve attention to fully achieve the translation of these advances to the clinic. PMID- 26903072 TI - Neutrophils in tuberculosis--first line of defence or booster of disease and targets for host-directed therapy? AB - Necrotizing granulomas, exacerbating pathogenesis and neutrophil influx at the site of infection are hallmarks of active pulmonary tuberculosis (TB) in humans. The role of polymorphonuclear neutrophils (PMN) in host defence and TB pathogenesis has recently attracted broader interest. Association of infiltrating PMN, enhanced mycobacterial load and disease exacerbation in both, mice susceptible to experimental TB as well as in TB patients, link PMN to exacerbated pathology. Targeting PMN resulted in smaller lung lesions and reduced mycobacterial burden. Therefore, PMN-associated molecules represent interesting biomarkers to determine TB severity and treatment success. More importantly, PMN are putative targets for host-directed therapies (HDT) in TB. Due to the rise of multi- and extensively drug-resistant Mycobacterium tuberculosis isolates, HDT represent adjunct measures to support antibiotic treatment by ameliorating pathology and local host defences. PMID- 26903073 TI - Acute disseminated encephalomyelitis presenting as a brainstem encephalitis. AB - Acute disseminated encephalomyelitis (ADEM) is a disease characterized by inflammation and destruction of myelin. Acute hemorrhagic leukoencephalitis (AHLE) is a severe form of ADEM known for its particularly poor outcome. We present a case of a young Caucasian female who presented with drowsiness and slurred speech followed by rapid brainstem involvement resembling rhomboencephalitis. Despite multiple diagnostic tests and empiric therapy with immunosuppressants, immunoglobulins, and antimicrobials, she lost most brainstem reflexes within a few weeks and ultimately passed away. Magnetic resonance imaging (MRI) showed progression of lesions from the brainstem to eventually involve bilateral cerebral hemispheres. Autopsy and microscopic examination of the brain revealed several hemorrhagic lesions throughout the brain and rendered a diagnosis of AHLE. AHLE was initially described in 1941 and is thought to be autoimmune related, possibly related to cross reactivity between the immune system and CNS tissues like myelin. While a definitive inciting pathogen was not discovered, this case emphasizes the importance of considering AHLE in the differential diagnosis of patients with rapid loss of neurologic function and highlights an atypical presentation of ADEM/AHLE. PMID- 26903075 TI - Association between psychosomatic health symptoms and common mental illness in Ghanaian adolescents: Age and gender as potential moderators. AB - Little is known about the role of age and gender in the association between psychosomatic symptoms and common mental illness in Ghanaian adolescents. This cross-sectional study examined age and gender as moderators between psychosomatic symptoms and common mental illness using data from a school-based survey ( N = 770). Males reported higher psychosomatic symptoms and common mental illness, while younger adolescents reported higher common mental illness only. Psychosomatic symptoms were positively associated with common mental illness, but age and gender did not moderate this association. Interventions aimed at reducing the prevalence rate in psychosomatic symptoms are crucial in decreasing common mental illness in Ghanaian adolescents. PMID- 26903074 TI - Conjugate eye deviation as predictor of acute cortical and subcortical ischemic brain lesions. AB - OBJECTIVES: Non-enhanced computed tomography (NECT) of the brain is used to exclude intracranial hemorrhage in patients who are considered for treatment with tissue plasminogen activator due to stroke symptoms. However, early infarct signs on NECT have low sensitivity for ischemic stroke. It was hypothesized that horizontal conjugate eye deviation (average ocular gaze deviation-OGD >14 degrees ) on NECT predicts ischemic brain injury on a second detailed examination. PATIENTS AND METHODS: Patients who underwent brain NECT within three hours after the onset of stroke symptoms and subsequently had brain CT scan with intravenous contrast or MRI were potential participants. OGD was measured from the cross sectional image including both globes at their maximum diameter. RESULTS: 73 subjects were studied (mean age 64.2+/-20.8 years) with a median interval (interquartile range) of 56 h (22-109.3 h) between NECT and the second examination. On NECT, 24 of 73 (32.9%) subjects had OGD >14 degrees . Of 32 individuals with acute ischemic injury on the second examination, 19 (59.4%) had OGD >14 degrees on NECT. OGD >14 degrees was associated with increased risk of ischemic injury: OR=10.5 (95% confidence interval 3.33-33.9); P=0.002. OGD >14 degrees had significantly higher sensitivity and negative predictive value than early infarct signs on NECT (59.4% vs. 21.9% and 73.5% vs. 59.7%, respectively; P<0.05), and similar specificity and positive predictive value (87.8% vs. 90.2% and 79.2% vs. 63.6%; P>0.05). CONCLUSION: In the presence of stroke symptoms, average OGD >14 degrees on the initial brain NECT is early predictor of ischemic brain injury. PMID- 26903077 TI - Spiritual development in Iranian nurses. AB - BACKGROUND: Spiritual development is one of the most important aspects of socialization that has attracted the attention of researchers. It is needed to train nursing student and novice nurses to provide high-quality care for patients. There is ambiguity in the definition of spiritual development and its relations, especially in the eastern countries. RESEARCH OBJECTIVES: To explore the concept of spiritual development in Iranian nurses. RESEARCH DESIGN: Qualitative content analysis approach. Data were gathered from semi-structured interviews. Participants and research context: The participants were 17 Iranian Muslim nurses selected using a purposeful sampling. The place of interviews was on their choice. Ethical considerations: Based on the principles of the Helsinki declaration, the focus was on preserving the participants' autonomy, confidentiality, and anonymity. The participants were told the study purposes and trends, and their rights were emphasized; they were then asked to sign written consent forms. Formal research approval was obtained from Kerman University of Medical Sciences. Ethical approval was granted by the University Ethics Committee before the study was conducted (K/92 etc). FINDINGS: Three themes for spiritual development were defined: obligation to religion, commitment to ethics, and commitment to law. From the results, factors such as connection to the limitless divine power, personal and society-oriented ethical codes, and commitment to the law are proposed. DISCUSSION: There are some differences between these findings and previous study, especially in the relation of the spirituality, religion, and law. Some studies, mostly Iranian, support these findings partially. CONCLUSION: The results suggest that it is better to teach nursing education based on humanistic principles, ethics, and law to the new generation of nurses to improve community health and development. More studies are needed to examine the relation between these themes. PMID- 26903076 TI - 'This place is making me more depressed': The organisation of care for suicide attempters in a South African hospital. AB - People who attend hospital following a suicide attempt represent a well delineated high-risk group of patients who may be amenable to targeted interventions to reduce the risk of suicidal behaviour. Little is, however, known about how hospitals in South Africa respond to suicide attempters, what quality of care these patients receive or what possibilities exist for hospital-based suicide prevention interventions. We describe an ethnographic study conducted at a large hospital in South Africa to investigate the impact of current procedures and practices on the care received by those who attempt suicide. Findings suggest that the organisation of care within the hospital is a significant barrier to patients receiving optimal care and represents a lost opportunity for suicide prevention. Findings highlight the mismatch between the needs of suicide attempters and current services and call attention to the need for greater psychological input as well as hospital-based suicide prevention interventions that can be offered to patients without necessitating admissions. PMID- 26903079 TI - Lipopolysaccharides attenuates growth of HS cells through the JNK pathway. AB - Rheumatoid arthritis is characterized by inflammation of the synovial membrane, which can result in joint destruction within the first few years after onset. Lipopolysaccharides (LPS) are glycolipids found in abundance on the outer membranes of all Gram-negative bacteria and incite a vigorous inflammatory response. We studied the potential involvement of mitogen-activated protein kinase serine/threonine kinases in LPS-induced growth of HS synovial cells. Various concentrations of LPS were applied to cultured HS cells and growth rate, as well as changes in the phosphorylation states of extracellular regulated kinase 1/2, Jun N-terminal kinase (JNK), and p38 were determined. As results, growth of LPS-treated HS cells was inhibited primarily by phosphorylated JNK and this phosphorylation was mediated by the LPS receptor. Our results suggest that LPS inhibits growth of HS cells primarily through the JNK pathway. PMID- 26903078 TI - Prefrontal NAA and Glx Levels in Different Stages of Psychotic Disorders: a 3T 1H MRS Study. AB - H-Magnetic Resonance Spectroscopy ((1)H-MRS) can offer insights in various neuropathologies by measuring metabolite levels in the brain. In the current study we investigated the levels of glutamate + glutamine (Glx, neurotransmitter and precursor) and N-Acetyl Aspartate + glutamic acid (NAA + NAAG; neuronal viability) in the prefrontal cortex of patients with a psychotic disorder and people at Ultra High Risk (UHR) for psychosis. A (1)H-MRS spectrum was acquired in 31 patients with a recent onset psychotic disorder and 60 with a chronic state, 16 UHR patients and 36 healthy controls. Absolute metabolite levels were calculated using LCModel with a reference water peak. Groups were compared while taking into account age and partial volume effects. Moreover, we investigated associations with positive and negative symptoms, duration of illness, and antipsychotic treatment in patients. The most notable finding is that chronicity of schizophrenia was related to decreased levels of Glx and NAA. On the other hand, although on an exploratory note, UHR showed increased levels of prefrontal Glx and NAA levels with increasing age. Our results may indicate an initial Glx and NAA increase and subsequent decrease during illness progression that may be related to the neurotoxic effects of glutamate. PMID- 26903080 TI - Homogeneous alignment of liquid crystalline dendrimers confined in a slit-pore. A simulation study. AB - In this work we present results from isobaric-isothermal (NPT) Monte Carlo simulation studies of model liquid crystalline dendrimer (LCDr) systems confined in a slit-pore made of two parallel flat walls. The dendrimers are modelled as a collection of spherical and ellipsoidal particles corresponding to the junction points of the dendritic core and to the mesogenic units respectively. Assuming planar uniform (unidirectional) soft anchoring of the mesogenic units on the substrates we investigate the conformational and alignment properties of the LCDr system at different thermodynamic state points. Tractable coarse grained force fields have been used from our previous work. At low pressures the interior of the pore is almost empty, since almost all LCDrs are anchored to the substrates forming two-dimensional smectic-like structures with the mesogens aligned along the aligning direction of the substrates. As the pressure grows the LCDrs occupy the whole pore. However, even at low temperatures, the smectic organization does not transmit in the interior of the pore and is preserved for distances of 2-3 mesogenic diameters from the walls. For this reason, the global orientational order decreases with increasing pressure (density). In the vicinity (2-3 mesogenic diameters) of the pore walls, mesogenic units preserve the smectic structure whose layers are separated by layers of spherical beads. In this region individual LCDrs possess a rod like shape. PMID- 26903081 TI - A Mind-Body Program for Older Adults With Chronic Low Back Pain: A Randomized Clinical Trial. AB - IMPORTANCE: Treatment of chronic low back pain (LBP) in older adults is limited by the adverse effects of analgesics. Effective nonpharmacologic treatment options are needed. OBJECTIVE: To determine the effectiveness of a mind-body program at increasing function and reducing pain in older adults with chronic LBP. DESIGN, SETTING, AND PARTICIPANTS: This single-blind, randomized clinical trial compared a mind-body program (n = 140) with a health education program (n = 142). Community-dwelling older adults residing within the Pittsburgh metropolitan area were recruited from February 14, 2011, to June 30, 2014, with 6-month follow up completed by April 9, 2015. Eligible participants were 65 years or older with functional limitations owing to their chronic LBP (>=11 points on the Roland and Morris Disability Questionnaire) and chronic pain (duration >=3 months) of moderate intensity. Data were analyzed from March 1 to July 1, 2015. INTERVENTIONS: The intervention and control groups received an 8-week group program followed by 6 monthly sessions. The intervention was modeled on the Mindfulness-Based Stress Reduction program; the control program, on the "10 Keys" to Healthy Aging. MAIN OUTCOMES AND MEASURES: Follow-up occurred at program completion and 6 months later. The score on the Roland and Morris Disability Questionnaire was the primary outcome and measured functional limitations owing to LBP. Pain (current, mean, and most severe in the past week) was measured with the Numeric Pain Rating Scale. Secondary outcomes included quality of life, pain self-efficacy, and mindfulness. Intent-to-treat analyses were conducted. RESULTS: Of 1160 persons who underwent screening, 282 participants enrolled in the trial (95 men [33.7%] and 187 women [66.3%]; mean [SD] age,74.5 [6.6] years). The baseline mean (SD) Roland and Morris Disability Questionnaire scores for the intervention and control groups were 15.6 (3.0) and 15.4 (3.0), respectively. Compared with the control group, intervention participants improved an additional -1.1 (mean, 12.1 vs 13.1) points at 8 weeks and -0.04 (mean, 12.2 vs 12.6) points at 6 months (effect sizes, -0.23 and -0.08, respectively) on the Roland and Morris Disability Questionnaire. By 6 months, the intervention participants improved on the Numeric Pain Rating Scale current and most severe pain measures an additional -1.8 points (95% CI, -3.1 to -0.05 points; effect size, -0.33) and 1.0 points (95% CI, -2.1 to 0.2 points; effect size, -0.19), respectively. The changes in Numeric Pain Rating Scale mean pain measure after the intervention were not significant (-0.1 [95% CI, -1.1 to 1.0] at 8 weeks and -1.1 [95% CI, 2.2 to -0.01] at 6 months; effect size, -0.01 and -0.22, respectively). CONCLUSIONS AND RELEVANCE: A mind-body program for chronic LBP improved short term function and long-term current and most severe pain. The functional improvement was not sustained, suggesting that future development of the intervention could focus on durability. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01405716. PMID- 26903082 TI - Development of a removable head fixation device for longitudinal behavioral and imaging studies in rats. AB - BACKGROUND: In some behavioral neuroscience studies, an attachment is surgically fixed onto the head of an awake animal to allow the animal to perform learning tasks repeatedly in the same position in a task-training system. A recently developed task-training system enables operant conditioning of head-fixed rats within only a few days, and this system has been rigorously applied to record learning-associated neural activity using electrophysiological techniques. However, the head attachment of this device is made of metal and thus is not suitable for simultaneous brain imaging studies with X-ray computed tomography (CT), magnetic resonance imaging (MRI) or positron emission tomography (PET). NEW METHOD: We developed a novel head fixation device with a removable attachment to position the rat head precisely in both imaging and training devices across different sessions. The device consisted of a removable attachment, a clamp and a stage, all of which were made of PET/MRI compatible acrylic resin. We tested the usefulness of the device with (18)F-fluorodeoxyglucose (FDG) PET and CT. RESULTS: The new device did not substantially affect (18)F-FDG PET images. Repositioning of the rat's head across sessions and experimenters was at a level of submillimeter accuracy. COMPARISON WITH EXISTING METHOD: The errors of radioactivity concentration of (18)F-FDG in the PET image were lower with the present attachment than with the conventional metal attachment. Repositioning accuracy was considerably improved compared with a visual inspection method. CONCLUSIONS: The developed fixation device is useful for longitudinal behavioral and brain imaging studies in rats. PMID- 26903083 TI - Enantioselective Copper-Catalyzed Formal [4 + 2] Cycloaddition of o-Aminophenol Derivatives with Propargylic Esters for Synthesis of Optically Active 3,4-Dihydro 2H-1,4-benzoxazines. AB - The first copper-catalyzed asymmetric formal [4 + 2] cycloaddition of o aminophenol derivatives with propargylic esters as the bis-electrophilic C2 synthons for the stereoselective construction of chiral 2,3,4-trisubstituted 2H 1,4-benzoxazines bearing an exocyclic double bond has been developed. By using a structurally modified chiral ketimine P,N,N-ligand, a wide range of optically active 2H-1,4-benzoxazines were prepared in high yields and with excellent enantioselectivities (up to 97% ee). PMID- 26903084 TI - Eye position effects on the remapped memory trace of visual motion in cortical area MST. AB - After a saccade, most MST neurons respond to moving visual stimuli that had existed in their post-saccadic receptive fields and turned off before the saccade ("trans-saccadic memory remapping"). Neuronal responses in higher visual processing areas are known to be modulated in relation to gaze angle to represent image location in spatiotopic coordinates. In the present study, we investigated the eye position effects after saccades and found that the gaze angle modulated the visual sensitivity of MST neurons after saccades both to the actually existing visual stimuli and to the visual memory traces remapped by the saccades. We suggest that two mechanisms, trans-saccadic memory remapping and gaze modulation, work cooperatively in individual MST neurons to represent a continuous visual world. PMID- 26903085 TI - The effect of ventilation tube insertion or trans-tympanic silicone plug insertion on a patulous Eustachian tube. AB - Conclusions This study suggests that long-term ventilation tube insertion is the first-choice surgical treatment for a 'sniff-type' patulous Eustachian tube (PET). When treating a refractory PET, it is important to determine whether the patient had a habitual sniff. Objectives PET patients were divided into two groups: patients with a habitual sniff (sniff-type PET) and those without a habitual sniff (non-sniff-type PET). This study examined the effects of ventilation tube insertion or silicone plug insertion in each group. Methods Surgical procedures such as ventilation tube insertion or trans-tympanic silicone plug insertion were performed for these patients. Tubotympanoaero-dynamic graphy (TTAG) was also performed to determine the mechanisms underlying these treatments. Results There were 11 cases (17 ears) of sniff-type PET and 20 cases (27 ears) of non-sniff-type PET. An improvement in symptoms was found in 72.7% of the patients who underwent silicone plug insertion (66.7% for sniff-type PET and 74.1% for non-sniff-type PET) and in 90.9% of the patients who underwent ventilation tube insertion for sniff-type PET. In TTAG assessments, many sniff type PET patients showed significant synchronous changes at high levels of pressure (over 40 daPa) in the external auditory meatus and nasopharynx when performing a slight Valsalva manoeuvre (below 200 daPa). PMID- 26903086 TI - Synthesis of TiO2-loaded Co0.85Se thin films with heterostructure and their enhanced catalytic activity for p-nitrophenol reduction and hydrazine hydrate decomposition. AB - P-nitrophenol (4-NP) and hydrazine hydrate are considered to be highly toxic pollutants in wastewater, and it is of great importance to remove them. Herein, TiO2-loaded Co0.85Se thin films with heterostructure were successfully synthesized by a hydrothermal route. The as-synthesized samples were characterized by x-ray diffraction, x-ray photoelectron spectroscopy, transmission electron microscopy and selective-area electron diffraction. The results demonstrate that TiO2 nanoparticles with a size of about 10 nm are easily loaded on the surface of graphene-like Co0.85Se nanofilms, and the NH3 . H2O plays an important role in the generation and crystallization of TiO2 nanoparticles. Brunauer-Emmett-Teller measurement shows that the obtained nanocomposites have a larger specific surface area (199.3 m(2) g(-1)) than that of Co0.85Se nanofilms (55.17 m(2) g(-1)) and TiO2 nanoparticles (19.49 m(2) g( 1)). The catalytic tests indicate Co0.85Se-TiO2 nanofilms have the highest activity for 4-NP reduction and hydrazine hydrate decomposition within 10 min and 8 min, respectively, compared with the corresponding precursor Co0.85Se nanofilms and TiO2 nanoparticles. The enhanced catalytic performance can be attributed to the larger specific surface area and higher rate of interfacial charge transfer in the heterojunction than that of the single components. In addition, recycling tests show that the as-synthesized sample presents stable conversion efficiency for 4-NP reduction. PMID- 26903088 TI - Comment on 'International collegium of rehabilitative audiology (ICRA) recommendations for the construction of multilingual speech tests', by Akeroyd et al. PMID- 26903087 TI - Efficacy of earphones for 12- to 24-month-old children during visual reinforcement audiometry. AB - OBJECTIVE: Efficacy of insert and supra-aural earphones during visual reinforcement audiometry (VRA) was investigated for 12- to 24-month-old children. DESIGN: VRA testing began in the soundfield and transitioned to either insert or supra-aural earphones. Audiologists recorded threshold estimates, participant behaviors, and an overall subjective rating of earphone acceptance. STUDY SAMPLE: One hundred and eighty-six 12- to 24-month-old children referred to the Department of Audiology at St. Louis Children's Hospital for a variety of reasons. RESULTS: Subjective ratings indicated high acceptance of insert earphones (84%) and supra-aural earphones (80%) despite negative behaviors. There was no significant difference in the number of threshold estimates based on earphone type for 12- to 17-month-old participants. Participants in the 18- to 24 month-old age group provided significantly more threshold estimates with insert earphones (mean = 5.3 threshold estimates, SD = 3.5) than with supra-aural earphones (mean = 2.9 threshold estimates, SD = 2.9). All seven participants who rejected earphone placement were successfully reconditioned for soundfield testing. CONCLUSIONS: Data support the use of insert earphones during VRA, especially with 18-to 24-month-old children, to obtain ear-specific information. PMID- 26903089 TI - Isomerization and Oligomerization of Truncated and Mutated Tau Forms by FKBP52 are Independent Processes. AB - The aggregation of the neuronal Tau protein is one molecular hallmark of Alzheimer's disease and other related tauopathies, but the precise molecular mechanisms of the aggregation process remain unclear. The FK506 binding protein FKBP52 is able to induce oligomers in the pathogenic Tau P301L mutant and in a truncated form of the wild-type human Tau protein. Here, we investigate whether FKBP52's capacity to induce Tau oligomers depends on its prolyl cis/trans isomerase activity. We find that FKBP52 indeed can isomerize selected prolyl bonds in the different Tau proteins, and that this activity is carried solely by its first FK506 binding domain. Its capacity to oligomerize Tau is, however, not linked to this peptidyl-prolyl isomerase activity. In addition, we identified a novel molecular interaction implying the PHF6 peptide of Tau and the FK1/FK2 domains of FKBP52 independent of FK506 binding; these data point toward a non catalytic molecular interaction that might govern the effect of FKBP52 on Tau. PMID- 26903090 TI - Ensemble Modeling and Intracellular Aggregation of an Engineered Immunoglobulin Like Domain. AB - The production of recombinant proteins in Escherichia coli frequently results in the formation of insoluble protein aggregates called inclusion bodies (IBs). The determinants of IB formation remain poorly understood and are of much interest for biotechnological and research applications, as well as offering insight into disease-related in vivo protein aggregation. Here we investigate a set of engineered target-binding proteins based upon the fibronectin type III domain, and we find that variations in sequence at just three positions in a solvent exposed loop greatly alter the extent of IB formation. The loop is analogous to the third complementarity-determining region of immunoglobulin variable domains and has been shown to be conformationally mobile. In contrast to studies of other proteins, the extent of IB formation is not explained by differences in thermal stability measured by differential scanning calorimetry. Instead, IB formation is correlated with the average local stability of the FG loop, as modeled by an ensemble of structures generated using Rosetta's kinematic closure loop reconstruction method. This correlation suggests that loop instability may promote local unfolding, exposing aggregation-prone surfaces. Consistent with this mechanism, sequence-based predictions of aggregation propensity produced by Zyggregator are also correlated with IB formation, though not with modeled loop stability. The combination of average model energy scores with sequence-based aggregation predictions accounts for the variation in IB formation remarkably well (R(2)=0.8). The comparison with experimental data validates the ensemble modeling approach, which may be applicable to dynamic protein loops involved in a wide range of phenomena. PMID- 26903091 TI - Fractal Fluctuations in Human Walking: Comparison Between Auditory and Visually Guided Stepping. AB - In human locomotion, sensorimotor synchronization of gait consists of the coordination of stepping with rhythmic auditory cues (auditory cueing, AC). AC changes the long-range correlations among consecutive strides (fractal dynamics) into anti-correlations. Visual cueing (VC) is the alignment of step lengths with marks on the floor. The effects of VC on the fluctuation structure of walking have not been investigated. Therefore, the objective was to compare the effects of AC and VC on the fluctuation pattern of basic spatiotemporal gait parameters. Thirty-six healthy individuals walked 3 * 500 strides on an instrumented treadmill with augmented reality capabilities. The conditions were no cueing (NC), AC, and VC. AC included an isochronous metronome. For VC, projected stepping stones were synchronized with the treadmill speed. Detrended fluctuation analysis assessed the correlation structure. The coefficient of variation (CV) was also assessed. The results showed that AC and VC similarly induced a strong anti-correlated pattern in the gait parameters. The CVs were similar between the NC and AC conditions but substantially higher in the VC condition. AC and VC probably mobilize similar motor control pathways and can be used alternatively in gait rehabilitation. However, the increased gait variability induced by VC should be considered. PMID- 26903093 TI - Linking the thermodynamic temperature to an optical frequency: recent advances in Doppler broadening thermometry. AB - Laser spectroscopy in the linear regime of radiation-matter interaction is a powerful tool for measuring thermodynamic quantities in a gas at thermodynamic equilibrium. In particular, the Doppler effect can be considered a gift of nature, linking the thermal energy to an optical frequency, namely the line centre frequency of an atomic or molecular spectral line. This is the basis of a relatively new method of primary gas thermometry, known as Doppler broadening thermometry (DBT). This paper reports on the efforts that have been carried out, in the last decade, worldwide, to the end of making DBT competitive with more consolidated and accurate methodologies, such as acoustic gas thermometry and dielectric constant gas thermometry. The main requirements for low-uncertainty DBT, of both theoretical and technical nature, will be discussed, with a special focus on those related to the line shape model and to the frequency scale. A deep comparison among the different molecules that have been selected in successful DBT implementations is also reported. Finally, for the first time, to the best of my knowledge, the influence of refractive index effects is discussed. PMID- 26903094 TI - Primary current-sensing noise thermometry in the millikelvin regime. AB - The use of low-temperature platforms with base temperatures below 1 K is rapidly expanding, for fundamental science, sensitive instrumentation and new technologies of potentially significant commercial impact. Precise measurement of the thermodynamic temperature of these low-temperature platforms is crucial for their operation. In this paper, we describe a practical and user-friendly primary current-sensing noise thermometer (CSNT) for reliable and traceable thermometry and the dissemination of the new kelvin in this temperature regime. Design considerations of the thermometer are discussed, including the optimization of a thermometer for the temperature range to be measured, noise sources and thermalization. We show the procedure taken to make the thermometer primary and contributions to the uncertainty budget. With standard laboratory instrumentation, a relative uncertainty of 1.53% is obtainable. Initial comparison measurements between a primary CSNT and a superconducting reference device traceable to the PLTS-2000 (Provisional Low Temperature Scale of 2000) are presented between 66 and 208 mK, showing good agreement within the k=1 calculated uncertainty. PMID- 26903095 TI - Meaning of temperature in different thermostatistical ensembles. AB - Depending on the exact experimental conditions, the thermodynamic properties of physical systems can be related to one or more thermostatistical ensembles. Here, we survey the notion of thermodynamic temperature in different statistical ensembles, focusing in particular on subtleties that arise when ensembles become non-equivalent. The 'mother' of all ensembles, the microcanonical ensemble, uses entropy and internal energy (the most fundamental, dynamically conserved quantity) to derive temperature as a secondary thermodynamic variable. Over the past century, some confusion has been caused by the fact that several competing microcanonical entropy definitions are used in the literature, most commonly the volume and surface entropies introduced by Gibbs. It can be proved, however, that only the volume entropy satisfies exactly the traditional form of the laws of thermodynamics for a broad class of physical systems, including all standard classical Hamiltonian systems, regardless of their size. This mathematically rigorous fact implies that negative 'absolute' temperatures and Carnot efficiencies more than 1 are not achievable within a standard thermodynamical framework. As an important offspring of microcanonical thermostatistics, we shall briefly consider the canonical ensemble and comment on the validity of the Boltzmann weight factor. We conclude by addressing open mathematical problems that arise for systems with discrete energy spectra. PMID- 26903096 TI - Progress towards the determination of thermodynamic temperature with ultra-low uncertainty. AB - Previous research effort towards the determination of the Boltzmann constant has significantly improved the supporting theory and the experimental practice of several primary thermometry methods based on the measurement of a thermodynamic property of a macroscopic system at the temperature of the triple point of water. Presently, experiments are under way to demonstrate their accuracy in the determination of the thermodynamic temperature T over an extended range spanning the interval between a few kelvin and the copper freezing point (1358 K). We discuss how these activities will improve the link between thermodynamic temperature and the temperature as measured using the International Temperature Scale of 1990 (ITS-90) and report some preliminary results obtained by dielectric constant gas thermometry and acoustic gas thermometry. We also provide information on the status of other primary methods, such as Doppler broadening thermometry, Johnson noise thermometry and refractive index gas thermometry. Finally, we briefly consider the implications of these advancements for the dissemination of calibrated temperature standards. PMID- 26903098 TI - Towards implementing the new kelvin. PMID- 26903097 TI - Dissemination of thermodynamic temperature above the freezing point of silver. AB - The mise-en-pratique for the definition of the kelvin at high temperatures will formally allow dissemination of thermodynamic temperature either directly or mediated through high-temperature fixed points (HTFPs). In this paper, these two distinct dissemination methods are evaluated, namely source-based and detector based. This was achieved by performing two distinct dissemination trials: one based on HTFPs, the other based on absolutely calibrated radiation thermometers or filter radiometers. These trials involved six national metrology institutes in Europe in the frame of the European Metrology Research Programme joint project 'Implementing the new kelvin' (InK). The results have shown that both dissemination routes are possible, with similar standard uncertainties of 1-2 K, over the range 1273-2773 K, showing that, depending on the facilities available in the laboratory, it will soon be possible to disseminate thermodynamic temperatures above 1273 K to users by either of the two methods with uncertainties comparable to the current temperature scale. PMID- 26903101 TI - Noise thermometry at ultra-low temperatures. AB - The options for primary thermometry at ultra-low temperatures are rather limited. In practice, most laboratories are using (195)Pt NMR thermometers in the microkelvin range. In recent years, current sensing direct current superconducting quantum interference devices (DC-SQUIDs) have enabled the use of noise thermometry in this temperature range. Such devices have also demonstrated the potential for primary thermometry. One major advantage of noise thermometry is the fact that no driving current is needed to operate the device and thus the heat dissipation within the thermometer can be reduced to a minimum. Ultimately, the intrinsic power dissipation is given by the negligible back action of the readout SQUID. For thermometry in low-temperature experiments, current noise thermometers and magnetic flux fluctuation thermometers have proved to be most suitable. To make use of such thermometers at ultra-low temperatures, we have developed a cross-correlation technique that reduces the amplifier noise contribution to a negligible value. For this, the magnetic flux fluctuations caused by the Brownian motion of the electrons in our noise source are measured inductively by two DC-SQUID magnetometers simultaneously and the signals from these two channels are cross-correlated. Experimentally, we have characterized a thermometer made of a cold-worked high-purity copper cylinder with a diameter of 5 mm and a length of 20 mm for temperatures between 42 MUK and 0.8 K. For a given temperature, a measuring time below 1 min is sufficient to reach a precision of better than 1%. The extremely low power dissipation in the thermometer allows continuous operation without heating effects. PMID- 26903100 TI - Towards high-accuracy primary spectral radiometry from 400 K to 1300 K. AB - We describe the design, construction, calibration and use of a near-infrared thermodynamic radiation thermometer to measure blackbodies from 400 K to 1300 K. The motivation for this work is the pending redefinition of the kelvin and the need for direct, thermodynamic temperature measurements of the fixed-point blackbodies presently used in the realization of the temperature scale. The challenges of accurately measuring Planck radiances which vary greatly in radiance level and spectral shape are discussed. Methods to characterize the components used in the radiation thermometer design are described. The use of this radiation thermometer as a relative primary thermometer and the resulting residuals are shown. We describe radiometric calibration procedures for using the radiation thermometer as an absolute primary thermometer. Preliminary data showing the initial radiometric calibration steps are discussed. PMID- 26903099 TI - Thermodynamic temperature assignment to the point of inflection of the melting curve of high-temperature fixed points. AB - The thermodynamic temperature of the point of inflection of the melting transition of Re-C, Pt-C and Co-C eutectics has been determined to be 2747.84 +/- 0.35 K, 2011.43 +/- 0.18 K and 1597.39 +/- 0.13 K, respectively, and the thermodynamic temperature of the freezing transition of Cu has been determined to be 1357.80 +/- 0.08 K, where the +/- symbol represents 95% coverage. These results are the best consensus estimates obtained from measurements made using various spectroradiometric primary thermometry techniques by nine different national metrology institutes. The good agreement between the institutes suggests that spectroradiometric thermometry techniques are sufficiently mature (at least in those institutes) to allow the direct realization of thermodynamic temperature above 1234 K (rather than the use of a temperature scale) and that metal-carbon eutectics can be used as high-temperature fixed points for thermodynamic temperature dissemination. The results directly support the developing mise en pratique for the definition of the kelvin to include direct measurement of thermodynamic temperature. PMID- 26903102 TI - Thermodynamic temperature by primary radiometry. AB - Above the freezing temperature of silver (1234.93 K), the International Temperature Scale of 1990 (ITS-90) gives a temperature, T90, in terms of a defining fixed-point blackbody and Planck's law of thermal radiation in ratio form. Alternatively, by using Planck's law directly, thermodynamic temperature can be determined by applying radiation detectors calibrated in absolute terms for their spectral responsivity. With the advent of high-quality semiconductor photodiodes and the development of high-accuracy cryogenic radiometers during the last two decades radiometric detector standards with very small uncertainties in the range of 0.01-0.02% have been developed for direct, absolute radiation thermometry with uncertainties comparable to those for the realization of the ITS 90. This article gives an overview of a number of design variants of different types of radiometer used for primary radiometry and describes their calibration. Furthermore, details and requirements regarding the experimental procedure for obtaining low uncertainty thermodynamic temperatures with these radiometers are presented, noting that such radiometers can also be used at temperatures well below the silver point. Finally, typical results obtained by these methods are reviewed. PMID- 26903103 TI - The kelvin redefinition and its mise en pratique. AB - In 2018, it is expected that there will be a major revision of the International System of Units (SI) which will result in all of the seven base units being defined by fixing the values of certain atomic or fundamental constants. As part of this revision, the kelvin, unit of thermodynamic temperature, will be redefined by assigning a value to the Boltzmann constant k. This explicit constant definition will define the kelvin in terms of the SI derived unit of energy, the joule. It is sufficiently wide to encompass any form of thermometry. The planned redefinition has motivated the creation of an extended mise en pratique ('practical realization') of the definition of the kelvin (MeP-K), which describes how the new definition can be put into practice. The MeP-K incorporates both of the defined International Temperature Scales (ITS-90 and PLTS-2000) in current use and approved primary-thermometry methods for determining thermodynamic temperature values. The MeP-K is a guide that provides or makes reference to the information needed to perform measurements of temperature in accord with the SI at the highest level. In this article, the background and the content of the extended second version of the MeP-K are presented. PMID- 26903104 TI - Estimates of the difference between thermodynamic temperature and the International Temperature Scale of 1990 in the range 118 K to 303 K. AB - Using exceptionally accurate measurements of the speed of sound in argon, we have made estimates of the difference between thermodynamic temperature, T, and the temperature estimated using the International Temperature Scale of 1990, T90, in the range 118 K to 303 K. Thermodynamic temperature was estimated using the technique of relative primary acoustic thermometry in the NPL-Cranfield combined microwave and acoustic resonator. Our values of (T-T90) agree well with most recent estimates, but because we have taken data at closely spaced temperature intervals, the data reveal previously unseen detail. Most strikingly, we see undulations in (T-T90) below 273.16 K, and the discontinuity in the slope of (T T90) at 273.16 K appears to have the opposite sign to that previously reported. PMID- 26903105 TI - A SQUID-based primary noise thermometer for low-temperature metrology. AB - Practical temperature measurements in accordance with the international system of units require traceability to the international temperature scales currently in force. Along with the awaited redefinition of the unit of temperature, the kelvin, on the basis of the Boltzmann constant, in future its mise en pratique will allow the use of approved methods of primary thermometry for the realization and dissemination of the kelvin. To support this process, we have developed a DC superconducting quantum interference device-based noise thermometer especially designed for measurements of thermodynamic temperature in a broad temperature range from 5 K down to below 1 mK. In this paper, we describe in detail the primary magnetic field fluctuation thermometer and the underlying model applied for the temperature determination. Experimental measurement results are presented for a comparison with the Provisional Low Temperature Scale 2000 between 0.7 K and 16 mK including an uncertainty budget for the measured thermodynamic temperatures. In this set-up, the relative combined standard uncertainty is equal to 0.6%. PMID- 26903106 TI - Acoustic and microwave tests in a cylindrical cavity for acoustic gas thermometry at high temperature. AB - Relative primary acoustic gas thermometry (AGT) determines the ratios of thermodynamic temperatures from measured ratios of acoustic and microwave resonance frequencies in a gas-filled metal cavity on isotherms of interest. When measured in a cavity with known dimensions, the frequencies of acoustic resonances in a gas determine the speed of sound, which is a known function of the thermodynamic temperature T. Changes in the dimensions of the cavity are measured using the frequencies of the cavity's microwave resonances. We explored techniques and materials for AGT at high temperatures using a cylindrical cavity with remote acoustic transducers. We used gas-filled ducts as acoustic waveguides to transmit sound between the cavity at high temperatures and the acoustic transducers at room temperature. We measured non-degenerate acoustic modes in a cylindrical cavity in the range 295 K=2.675 g/L were the independent prognostic predictors of tumor recurrence and poor outcome. CONCLUSIONS: Pretransplant elevated fibrinogen levels are associated with tumor recurrence and poor prognosis in hepatocellular carcinoma patients after liver transplantation. PMID- 26903140 TI - A meta-analysis of chemokines in major depression. AB - Chemokines are increasingly recognised as playing a role in depression. Here we meta-analyse the data on concentrations of all chemokines in patients diagnosed with a major depression versus healthy controls. We included studies which utilised Diagnostic and Statistical Manual (DSM)-IV diagnostic criteria for major depression, participants free from major medical conditions, studies with healthy controls, and unstimulated measurements of chemokines. We only included chemokines which had >=3 studies performed. Two chemokines and 15 studies in total met criteria for this meta-analysis; 8 for Monocyte Chemotactic Protein (MCP)-1/CCL2 (n=747), and 7 for Interleukin (IL)-8/CXCL8 (n=560). There were significantly higher concentrations of CCL2/MCP-1 in depressed subjects compared with control subjects - overall mean difference of 36.43pg/mL (95% CI: 2.43 to 70.42). There was significant heterogeneity across these studies (I2=98.5%). The estimates of mean difference between the control and depression groups did not remain significant when the trim-and-fill procedure was used to correct for publication bias. There was no significant difference in concentrations of IL 8/CXCL8 in depressed subjects compared with control subjects. Significant heterogeneity was found across these studies (I2=96.7%). The estimates of mean difference between the control and depression groups remained non-significant when the trim-and-fill procedure was used to correct for publication bias. This meta-analysis reports significantly heterogeneity in this field among studies. There are higher concentrations of the chemokine MCP-1/CCL2 in depressed subjects compared with control subjects, and no differences for IL-8/CXCL8. More high quality research and consistent methodologies are needed in this important area of enquiry. PMID- 26903142 TI - Disaster Preparedness among Active Duty Personnel, Retirees, Veterans, and Dependents. AB - BACKGROUND: With the increase in natural and manmade disasters, preparedness remains a vital area of concern. Despite attempts by government and non government agencies to stress the importance of preparedness, national levels of preparedness remain unacceptably low. A goal of commands and installations is to ensure that US Navy beneficiaries are well prepared for disasters. This especially is critical in active service members to meet mission readiness requirements in crisis settings. OBJECTIVE: To evaluate active duty Navy personnel, dependents, veterans, and retirees regarding disaster preparedness status. METHODS: The authors conducted an anonymous 29-question survey for US Navy active duty, dependents, veterans, and retirees of the Greater San Diego Region (California, USA) evaluating actual basic disaster readiness as determined by the Federal Emergency Management Agency (FEMA) standards of 3-day minimum supply of emergency stores and equipment. Descriptive statistics and regression analysis were used to analyze data. RESULTS: One thousand one hundred and fifty surveys were returned and analyzed. Nine hundred and eight-three were sufficiently complete for logistic regression analysis with 394 responding "Yes" to having a 72-hour disaster kit (40.1%) while 589 had "No" as a response (59.9%). CONCLUSION: The surveyed population is no more prepared than the general public, though surveyed beneficiaries overall are at an upper range of preparedness. Lower income and levels of education were associated with lack of preparedness, whereas training in disaster preparedness or having been affected by disasters increased the likelihood of being adequately prepared. Unlike results seen in the general public, those with chronic health care needs in the surveyed population were more, rather than less, likely to be prepared and those with minor children were less likely, rather than more likely, to be prepared. Duty status was assessed and only veterans were emphatically more probable than most to be prepared. PMID- 26903141 TI - The adenosine metabolite inosine is a functional agonist of the adenosine A2A receptor with a unique signaling bias. AB - Inosine is an endogenous purine nucleoside that is produced by catabolism of adenosine. Adenosine has a short half-life (approximately 10s) and is rapidly deaminated to inosine, a stable metabolite with a half-life of approximately 15h. Resembling adenosine, inosine acting through adenosine receptors (ARs) exerts a wide range of anti-inflammatory and immunomodulatory effects in vivo. The immunomodulatory effects of inosine in vivo, at least in part, are mediated via the adenosine A2A receptor (A2AR), an observation that cannot be explained fully by in vitro pharmacological characterization of inosine at the A2AR. It is unclear whether the in vivo effects of inosine are due to inosine or a metabolite of inosine engaging the A2AR. Here, utilizing a combination of label-free, cell based, and membrane-based functional assays in conjunction with an equilibrium agonist-binding assay we provide evidence for inosine engagement at the A2AR and subsequent activation of downstream signaling events. Inosine-mediated A2AR activation leads to cAMP production with an EC50 of 300.7MUM and to extracellular signal-regulated kinase-1 and -2 (ERK1/2) phosphorylation with an EC50 of 89.38MUM. Our data demonstrate that inosine produces ERK1/2-biased signaling whereas adenosine produces cAMP-biased signaling at the A2AR, highlighting pharmacological differences between these two agonists. Given the in vivo stability of inosine, our data suggest an additional, previously unrecognized, mechanism that utilizes inosine to functionally amplify and prolong A2AR activation in vivo. PMID- 26903143 TI - Home-Based Versus Laboratory-Based Robotic Ankle Training for Children With Cerebral Palsy: A Pilot Randomized Comparative Trial. AB - OBJECTIVE: To examine the outcomes of home-based robot-guided therapy and compare it to laboratory-based robot-guided therapy for the treatment of impaired ankles in children with cerebral palsy. DESIGN: A randomized comparative trial design comparing a home-based training group and a laboratory-based training group. SETTING: Home versus laboratory within a research hospital. PARTICIPANTS: Children (N=41) with cerebral palsy who were at Gross Motor Function Classification System level I, II, or III were randomly assigned to 2 groups. Children in home-based and laboratory-based groups were 8.7+/-2.8 (n=23) and 10.7+/-6.0 (n=18) years old, respectively. INTERVENTIONS: Six-week combined passive stretching and active movement intervention of impaired ankle in a laboratory or home environment using a portable rehabilitation robot. MAIN OUTCOME MEASURES: Active dorsiflexion range of motion (as the primary outcome), mobility (6-minute walk test and timed Up and Go test), balance (Pediatric Balance Scale), Selective Motor Control Assessment of the Lower Extremity, Modified Ashworth Scale (MAS) for spasticity, passive range of motion (PROM), strength, and joint stiffness. RESULTS: Significant improvements were found for the home-based group in all biomechanical outcome measures except for PROM and all clinical outcome measures except the MAS. The laboratory-based group also showed significant improvements in all the biomechanical outcome measures and all clinical outcome measures except the MAS. There were no significant differences in the outcome measures between the 2 groups. CONCLUSIONS: These findings suggest that the translation of repetitive, goal-directed, biofeedback training through motivating games from the laboratory to the home environment is feasible. The benefits of home-based robot-guided therapy were similar to those of laboratory based robot-guided therapy. PMID- 26903144 TI - Measuring Access to Information and Technology: Environmental Factors Affecting Persons With Neurologic Disorders. AB - OBJECTIVE: To develop and validate a patient-reported measure of access to information and technology (AIT) for persons with spinal cord injury, stroke, or traumatic brain injury. DESIGN: A mixed-methods approach was used to develop items, refine them through cognitive interviews, and evaluate their psychometric properties. Item responses were evaluated with the Rasch rating scale model. Correlational and analysis-of-variance methods were used to evaluate construct validity. SETTING: Community-dwelling individuals participated in telephone interviews or traveled to the academic medical centers where this research took place. PARTICIPANTS: Individuals with a diagnosis of spinal cord injury, stroke, or traumatic brain injury (aged >=18y, English speaking) participated in cognitive interviews (n=12 persons), field testing of the items (n=305 persons), and validation testing of the final set of items (n=604 persons). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: A set of items to measure AIT for people with disabilities. RESULTS: A user-friendly multimedia touchscreen was used for self-administration of the items. A 23-item AIT measure demonstrated good evidence of internal consistency reliability, and content and construct validity. CONCLUSIONS: This new AIT measure will enable researchers and clinicians to determine to what extent environmental factors influence health outcomes and social participation in people with disabilities. The AIT measure could also provide disability advocates with more specific and detailed information about environmental factors to lobby for elimination of barriers. PMID- 26903145 TI - Swimming Improves Pain and Functional Capacity of Patients With Fibromyalgia: A Randomized Controlled Trial. AB - OBJECTIVE: To evaluate the effect of swimming on pain, functional capacity, aerobic capacity, and quality of life in patients with fibromyalgia (FM). DESIGN: Randomized controlled trial. SETTING: Rheumatology outpatient clinics of a university hospital. PARTICIPANTS: Women with FM (N=75; age range, 18-60y) randomly assigned to a swimming group (SG) (n=39) or a walking group (WG) (n=36). INTERVENTION: The SG performed 50 minutes of swimming 3 times a week for 12 weeks, with a heart rate at 11 beats under the anaerobic threshold. The WG performed walking with a heart rate at the anaerobic threshold, with the same duration and frequency as the SG. MAIN OUTCOME MEASURES: Participants were evaluated before the exercise protocols (t0), at 6 weeks (t6), and at 12 weeks (t12) after the onset of the protocols. The primary outcome measure was the visual analog scale for pain. The secondary measurements were the Fibromyalgia Impact Questionnaire and the Medical Outcomes Study 36-Item Short-Form Health Survey for quality of life; a spiroergometric test for cardiorespiratory variables; and the timed Up & Go test for functional performance. RESULTS: Patients in both groups experienced improvement in pain after the 12-week program, with no difference between groups (P=.658). The same results were found regarding functional capacity and quality of life. Moreover, no statistical difference between groups was found regarding aerobic capacity over time. CONCLUSIONS: Swimming, like walking, is an effective method for reducing pain and improving both functional capacity and quality of life in patients with FM. PMID- 26903146 TI - What Are the Determinants of Specialized Outpatient and Dental Care Use in Adults With Disabilities Living in Institutions: Findings From a National Survey in France. AB - OBJECTIVE: To explore the determinants of specialized outpatient care use (general practitioners excluded) in people with disabilities living in institutions. DESIGN: Cross-sectional study. SETTING: National health and disability survey. PARTICIPANTS: People (N=2528) living in institutions for adults with cognitive, sensory, and mobility disabilities. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: We used different measures of disability severity available in the survey: (1) the continuous score of limitations based on a measure we constructed according to self-reported level of difficulty performing 18 tasks without aid; (2) the Katz Index; and (3) the respondent's self-reported perception of functional limitations. Logistic regressions were performed to examine the determinants of the likelihood of having consulted a specialized outpatient care physician or a dentist at least once in the previous year. RESULTS: Of the 2528 individuals, 45% (1141) and 28% (697) had respectively consulted a specialized outpatient care physician or a dentist at least once in the previous year. After adjusting for health care needs, higher functional limitation scores, dependency in all 6 activities of daily living, and self reported perceptions of severe functional limitations were significantly associated with a lower likelihood of having consulted a specialized outpatient care physician (adjusted odds ratio [AOR], .95 [95% confidence interval {CI}, .94 .96]; AOR, .29 [95% CI, .23-.38]; and AOR, .51 [95% CI, .42-.62], respectively) or a dentist (AOR, .95 [95% CI, .94-.96]; AOR, .29 [95% CI, .21-.39]; AOR, .55 [95% CI, .44-.67], respectively) at least once in the previous year. Being a man, reporting a lack of family support, and having a low socioeconomic status also significantly affected specialized outpatient care use. CONCLUSIONS: Regardless of the method used to define and measure disability, a high degree of disability negatively affects specialized outpatient care use after adjusting for health care need. Further studies are needed to better understand the reasons why this association between the degree of functional limitation and unmet medical needs is also a reality for people with disabilities living in institutions. PMID- 26903147 TI - Effects of Twice-Weekly Intense Aerobic Exercise in Early Subacute Stroke: A Randomized Controlled Trial. AB - OBJECTIVE: To examine the effects of 12 weeks of twice-weekly intensive aerobic exercise on physical function and quality of life after subacute stroke. DESIGN: Randomized controlled trial. SETTING: Ambulatory care. PARTICIPANTS: Patients (N=56; 28 women) aged >=50 years who had a mild stroke (98% ischemic) and were discharged to independent living and enrolled 20 days (median) after stroke onset. INTERVENTIONS: Sixty minutes of group aerobic exercise, including 2 sets of 8 minutes of exercise with intensity up to exertion level 14 or 15 of 20 on the Borg rating of perceived exertion scale, twice weekly for 12 weeks (n=29). The nonintervention group (n=27) received no organized rehabilitation or scheduled physical exercise. MAIN OUTCOME MEASURES: Primary outcome measures included aerobic capacity on the standard ergometer exercise stress test (peak work rate) and walking distance on the 6-minute walk test (6MWT). Secondary outcome measures included maximum walking speed for 10m, balance on the timed Up and Go (TUG) test and single leg stance (SLS), health-related quality of life on the European Quality of Life Scale (EQ-5D), and participation and recovery after stroke on the Stroke Impact Scale (SIS) version 2.0 domains 8 and 9. Participants were evaluated pre- and postintervention. Patient-reported measures were also evaluated at 6-month follow-up. RESULTS: The following improved significantly more in the intervention group (pre- to postintervention): peak work rate (group * time interaction, P=.006), 6MWT (P=.011), maximum walking speed for 10m (P<.001), TUG test (P<.001), SLS right and left (eyes open) (P<.001 and P=.022, respectively), and SLS right (eyes closed) (P=.019). Aerobic exercise was associated with improved EQ-5D scores (visual analog scale, P=.008) and perceived recovery (SIS domain 9, P=.002). These patient-reported improvements persisted at 6-month follow-up. CONCLUSIONS: Intensive aerobic exercise twice weekly early in subacute mild stroke improved aerobic capacity, walking, balance, health-related quality of life, and patient-reported recovery. PMID- 26903148 TI - Errata: Visualizing biofilm formation in endotracheal tubes using endoscopic three-dimensional optical coherence tomography. PMID- 26903149 TI - An integrated lipidomics and metabolomics reveal nephroprotective effect and biochemical mechanism of Rheum officinale in chronic renal failure. AB - Chronic renal failure (CRF) is a major public health problem worldwide. Earlier studies have revealed salutary effects of rhubarb extracts in CRF. In this study, we employed lipidomic and metabolomic approaches to identify the plasma biomarkers and to determine the effect of treatment with petroleum ether, ethyl acetate and n-butanol extracts of rhubarb in a rat model of CRF with adenine induced chronic tubulointerstitial nephropathy. In addition, clinical biochemistry, histological evaluation and pro-fibrotic protein expression were analyzed. Significant changes were found between the CRF and control groups representing characteristic phenotypes of rats with CRF. Treatment with the three rhubarb extracts improved renal injury and dysfunction, either fully or partially reversed the plasma metabolites abnormalities and attenuated upregulation of pro fibrotic proteins including TGF-beta1, alpha-SMA, PAI-1, CTGF, FN and collagen-1. The nephroprotective effect of ethyl acetate extract was better than other extracts. The differential metabolites were closely associated with glycerophospholipid, fatty acid and amino acid metabolisms. The results revealed a strong link between renal tubulointerstitial fibrosis and glycerophospholipid metabolism and L-carnitine metabolism in the development of CRF. Amelioration of CRF with the three rhubarb extracts was associated with the delayed development and/or reversal the disorders in key metabolites associated with adenine-induced CRF. PMID- 26903151 TI - Gut-Brain Axis in Gastric Mucosal Damage and Protection. AB - BACKGROUND: The gut-brain axis plays a potential role in numerous physiological and pathological conditions. Several substances link stomach with central nervous system. In particular, hypothalamo-pituitary-adrenocortical axis, thyrotropinreleasing factor-containing nerve fibers and capsaicin-sensitive nerves are principal mediators of the harmful and protective central nervous system-mediated effects on gastric mucosa. Also, existing evidence indicates that nitric oxide, prostaglandins and calcitonin gene-related peptide play a role as final effectors of gastric protection. METHODS: We undertook a structured search of bibliographic databases for peerreviewed research literature with the aim of focusing on the role of gut-brain axis in gastric damage and protection. In particular, we examined manuscripts dealing with the role of steroids, thyrotropin-releasing hormone, prostaglandins, melatonin, hydrogen sulfide and peptides influencing food intake (i.e. leptin, cholecystokinin, peptide YY, central glucagon-like peptide-1, and ghrelin). Also, the role of GABAergic and glutamatergic pathways in gastric mucosal protection have been examined. RESULTS: We found and reviewed 61 peer-reviewed papers dealing with the major aspects related to the role of gut brain axis in gastric mucosal damage and protection. CONCLUSIONS: A dense neuronal network links stomach with central nervous system and a number of neurotransmitters and peptides functionally and anatomically related to central nervous system play a major role in contributing to gastric mucosal integrity. Exploiting the mechanisms underlying the connection between brain and gut may lead to a better understanding of the pathophysiology of gastric mucosal injury and to an improvement in the prevention and, eventually, management of gastric damage. PMID- 26903152 TI - Mining association patterns of drug-interactions using post marketing FDA's spontaneous reporting data. AB - BACKGROUND AND OBJECTIVES: Pharmacovigilance (PhV) is an important clinical activity with strong implications for population health and clinical research. The main goal of PhV is the timely detection of adverse drug events (ADEs) that are novel in their clinical nature, severity and/or frequency. Drug interactions (DI) pose an important problem in the development of new drugs and post marketing PhV that contribute to 6-30% of all unexpected ADEs. Therefore, the early detection of DI is vital. Spontaneous reporting systems (SRS) have served as the core data collection system for post marketing PhV since the 1960s. The main objective of our study was to particularly identify signals of DI from SRS. In addition, we are presenting an optimized tailored mining algorithm called "hybrid Apriori". METHODS: The proposed algorithm is based on an optimized and modified association rule mining (ARM) approach. A hybrid Apriori algorithm has been applied to the SRS of the United States Food and Drug Administration's (U.S. FDA) adverse events reporting system (FAERS) in order to extract significant association patterns of drug interaction-adverse event (DIAE). We have assessed the resulting DIAEs qualitatively and quantitatively using two different triage features: a three-element taxonomy and three performance metrics. These features were applied on two random samples of 100 interacting and 100 non-interacting DIAE patterns. Additionally, we have employed logistic regression (LR) statistic method to quantify the magnitude and direction of interactions in order to test for confounding by co-medication in unknown interacting DIAE patterns. RESULTS: Hybrid Apriori extracted 2933 interacting DIAE patterns (including 1256 serious ones) and 530 non-interacting DIAE patterns. Referring to the current knowledge using four different reliable resources of DI, the results showed that the proposed method can extract signals of serious interacting DIAEs. Various association patterns could be identified based on the relationships among the elements which composed a pattern. The average performance of the method showed 85% precision, 80% negative predictive value, 81% sensitivity and 84% specificity. The LR modeling could provide the statistical context to guard against spurious DIAEs. CONCLUSIONS: The proposed method could efficiently detect DIAE signals from SRS data as well as, identifying rare adverse drug reactions (ADRs). PMID- 26903150 TI - Nanotechnology Applications for Diffuse Intrinsic Pontine Glioma. AB - Diffuse intrinsic pontine gliomas (DIPGs) are invariably fatal tumors found in the pons of elementary school aged children. These tumors are grade II-IV gliomas, with a median survival of less than 1 year from diagnosis when treated with standard of care (SOC) therapy. Nanotechnology may offer therapeutic options for the treatment of DIPGs. Multiple nanoparticle formulations are currently being investigated for the treatment of DIPGs. Nanoparticles based upon stable elements, polymer nanoparticles, and organic nanoparticles are under development for the treatment of brain tumors, including DIPGs. Targeting of nanoparticles is now possible as delivery techniques that address the difficulty in crossing the blood brain barrier (BBB) are developed. Theranostic nanoparticles, a combination of therapeutics and diagnostic nanoparticles, improve imaging of the cancerous tissue while delivering therapy to the local region. However, additional time and attention should be directed to developing a nanoparticle delivery system for treatment of the uniformly fatal pediatric disease of DIPG. PMID- 26903153 TI - A user-centered model for designing consumer mobile health (mHealth) applications (apps). AB - BACKGROUND: Mobile technologies are a useful platform for the delivery of health behavior interventions. Yet little work has been done to create a rigorous and standardized process for the design of mobile health (mHealth) apps. This project sought to explore the use of the Information Systems Research (ISR) framework as guide for the design of mHealth apps. METHODS: Our work was guided by the ISR framework which is comprised of 3 cycles: Relevance, Rigor and Design. In the Relevance cycle, we conducted 5 focus groups with 33 targeted end-users. In the Rigor cycle, we performed a review to identify technology-based interventions for meeting the health prevention needs of our target population. In the Design Cycle, we employed usability evaluation methods to iteratively develop and refine mock-ups for a mHealth app. RESULTS: Through an iterative process, we identified barriers and facilitators to the use of mHealth technology for HIV prevention for high-risk MSM, developed 'use cases' and identified relevant functional content and features for inclusion in a design document to guide future app development. Findings from our work support the use of the ISR framework as a guide for designing future mHealth apps. DISCUSSION: Results from this work provide detailed descriptions of the user-centered design and system development and have heuristic value for those venturing into the area of technology-based intervention work. Findings from this study support the use of the ISR framework as a guide for future mHealth app development. CONCLUSION: Use of the ISR framework is a potentially useful approach for the design of a mobile app that incorporates end-users' design preferences. PMID- 26903155 TI - Structure-property relationships in two-dimensionally extended benzoporphyrin molecules probed using single-molecule fluorescence spectroscopy. AB - The photophysical properties of a series of highly pi-conjugated benzoporphyrin molecules (s) with different shapes were investigated in the condensed phase using single-molecule fluorescence spectroscopy. The fluorescence properties of single s were found to be affected by the number of porphyrin units and their molecular shapes. Notably, the single-molecule fluorescence dynamics of the s revealed an increase in the fluorescence lifetimes and blue shifts of the fluorescence spectra indicative of decreasing pi-conjugation pathways in the molecules. The distributions of the spectroscopic parameters and the photostability for the molecules also suggest conformational complexities and heterogeneities. Specifically, as the number of constituent porphyrin units increased, the one-step photobleaching behavior ratio and photostability decreased, and the spectroscopic parameter distributions broadened. The structural properties of the s were also directly determined using defocused wide field imaging and linear dichroism analyses. In particular, molecules with the same number of constituent porphyrins but different molecular shapes exhibited distinct photophysical properties. In summary, these observations provide guidance for the design of molecular systems that can enhance the performance of molecular electronic devices. PMID- 26903154 TI - Three-Dimensional Characterization of Mechanical Interactions between Endothelial Cells and Extracellular Matrix during Angiogenic Sprouting. AB - We studied the three-dimensional cell-extracellular matrix interactions of endothelial cells that form multicellular structures called sprouts. We analyzed the data collected in-situ from angiogenic sprouting experiments and identified the differentiated interaction behavior exhibited by the tip and stalk cells. Moreover, our analysis of the tip cell lamellipodia revealed the diversity in their interaction behavior under certain conditions (e.g., when the heading of a sprout is switched approximately between the long-axis direction of two different lamellipodia). This study marks the first time that new characteristics of such interactions have been identified with shape changes in the sprouts and the associated rearrangements of collagen fibers. Clear illustrations of such changes are depicted in three-dimensional views. PMID- 26903156 TI - Organocatalytic Site-Selective Acylation of 10-Deacetylbaccatin III. AB - Organocatalytic site-selective diversification of 10-deacetylbaccatin III, a key natural product for the semisynthesis of taxol, has been achieved. Various acyl groups were selectively introduced into the C(10)-OH of 10-deacetylbaccatin III. The C(10)-OH selective acylation was also applied to acylative site-selective dimerization of 10-deacetylbaccatin III to provide the structurally defined dimer. PMID- 26903157 TI - [SIRT1 Influences the Sensitivity of A549 Non-small Cell Lung Cancer Cell Line to ?Cisplatin via Modulating the Noxa Expression]. AB - BACKGROUND: The resistance of non-small cell lung cancer cells to cisplant is a common clinical phenomenon which could induce a poor therapeutic effect and should be difficult problem to be solved. SIRT1 and Noxa expression are associated with the chemotherapy for tumors. The present study focused on how SIRT1 expression influence the senstivity of non-small cell lung cancer cells and dissected the potential mechanism involved with Noxa. METHODS: The difference of SIRT1 and Noxa expression between A549 cells and A549/DDP cells was detected by real-time quantitative PCR (qRT-PCR) and Western blot. SIRT1 targeted siRNA was uesed to inhibit the SIRT1 expression in A549/DDP, after transfection, Cell Titer Blue assay, flow cytometry were performed to analyze the cell viability, cell cycle and cell apoptosis in order to reveal the effect of inhibition of SIRT1 on sensitivity of A549/DDP cells to cisplant. Moreover, the expression changes of Noxa in A549/DDP cells after siRNA treatment were detected by qRT-PCR and Western blot. RESULTS: There was a significant difference in senstivity to cisplant between A549 and A549/DDP cells. Compared with A549 cells, the A549/DDP cells showed a higher SIRT1 expression and lower Noxa expression. After transfected with SIRT1 targeted siRNA, the cell viability decreased accompanied with a increasing apoptosis rate, meanwhile, higher percent of G2/M phase was detected after the 4 MUg/mL cisplant treatment. Further more, inhibition of SIRT1 could induce the Noxa expression in A549/DDP cells. CONCLUSIONS: Higher SIRT1 expression may induce resistance to cisplant in A549 cells. SIRT1 inhibition may improve the sensitivity of A549/DDP cells to cisplantin though modulating the Noxa expression.?. PMID- 26903158 TI - [Hsp90AB1 Protein is Overexpressed in Non-small Cell Lung Cancer Tissues ?and Associated with Poor Prognosis in Lung Adenocarcinoma Patients]. AB - BACKGROUND: Heat shock protein 90 kDa alpha, class B member 1 (Hsp90AB1) is highly conserved ATP-dependent molecular chaperone, and over-expressed in a variety of tumor cells. Some molecules that play important roles in tumor development signaling pathways such as epidermal growth factor receptor (EGFR), human epidermal growth factor receptor-2 (HER2) are Hsp90AB1 client proteins. Hsp90AB1 interact with these client proteins and participate in a variety of pathophysiological processes of cells. The aim of this study is to detect the expression of Hsp90AB1 in non-small cell lung cancer (NSCLC) tissues, and explore its clinical significance. METHODS: The expression of Hsp90AB1 in 213 NSCLC tissues and 147 normal lung tissues was detected by tissue microarray and immunohistochemical staining method, and the relationship of Hsp90AB1 expression with clinicopathological parameters and prognosis of NSCLC patients were analyzed. RESULTS: The expression level of Hsp90AB1 in lung cancer tissues (positive rate of 54.0%) was significantly higher than that in normal lung tissue (positive rate of 0.0%, P<0.001). The positive expression rate of Hsp90AB1 in lung adenocarcinoma tissues (61.2%) was significantly higher than that in lung squamous cell carcinoma tissues (37.9%)(P=0.002), and its over-expression was associated with poor prognosis in lung adenocarcinoma patients (P=0.032). The expression level of Hsp90AB1 had no significant correlation with clinical stage, lymph node metastasis, pathological grade or other factors (P>0.05). CONCLUSIONS: Hsp90AB1 protein was over-expressed in NSCLC tissues, and was associated with lung cancer pathological type and overall survival in lung adenocarcinoma patients. PMID- 26903160 TI - [Analysis and Forecasting of Population Mortality and Life Lost Trend due to ?Lung Cancer among Xiamen Residents]. AB - BACKGROUND: In recent years, the incidence and mortality of lung cancer is rising. It has become the leading cause of death of malignant tumors in China. The aim of this study is to explore the trend of mortality and years of life lost due to lung cancer in residents in Xiamen, so as to provide the basis data on preventing lung cancer in Xiamen. METHODS: The data of residents in Xiamen dying of lung cancer from 2005 to 2014 was collected and cleared up to calculate the evaluation indexes including the mortality rate, the average potential life lost (AYLL), and the average percentage change (APC) of mortality rate. GM(1,1) model was used to predict the future mortality and AYLL. RESULTS: From 2005 to 2014, the average mortality rate of lung cancer in residents in Xiamen was 28.58 per 100,000 persons, of which in male was 2.90 times as that in female. The APC was 4.86%. The AYLL, which was 7.8 years, had decline trend from 2005 to 2014. The mean absolute percentage errors between observed values and fitted values were 2.16%-8.83%. The mortality rate and AYLL of lung cancer in residents in Xiamen would increase from 2015 to 2019. CONCLUSIONS: The mortality of lung cancer increased year by year in Xiamen. There are both increasing trend of mortality and years of life lost in future. So we should pay more attentions on preventing and curing of lung cancer. PMID- 26903159 TI - [Clinical Epidemiology and Histological Characteristics of 3,663 Lung Cancer Patients in Sichuan Province from 2008 to 2013]. AB - BACKGROUND: Lung cancer is the most common malignancy and is the leading cause of cancer-related death worldwide. Thus, this disease severely threatens human health. This study aims to identify the clinical epidemiology and histological characteristics of lung cancer patients in Sichuan areas. METHODS: We enrolled 3,761 lung-cancer patients who were identified as residents of Sichuan province and treated in West China Hospital from 2008 to 2013. RESULTS: A total of 3,663 patients from Central, Southern, North, and Western areas in Sichuan province, respectively, were enrolled. The average age of patients was 59.6 years, and patients were predominantly male (68.4%). Significant statistical differences were observed among the average age of patients, male, and pathological types in different regions (all P<0.05). In addition, compared with the 2008 group, the 2013 group had lower rates of adenocarcinoma and squamous-cell carcinoma but higher rates of early-stage lung cancer and lymph-node metastasis. After a three year follow-up of 1,003 cases, results showed that the 3-year overall survival (OS) was not the same in different regions (P=0.021), and that the poorest OS was in Western Sichuan. This result may be related to the high rate of patients with palliative care. CONCLUSIONS: For the last six years, the patients with lung cancer in Sichuan were mainly from Central Sichuan, male patients, elder (age > 60 yr) patients, and with adenocarcinoma of the lung. Patients of 2013 had lower rates of adenocarcinoma and squamous-cell carcinoma but higher rates of early stage lung cancer and lymph-node metastasis. Furthermore, the 3-year OS was not the same in different regions. PMID- 26903161 TI - [Clinical Analysis of 22 Cases of Pulmonary Large Cell Neuroendocrine Cancer]. AB - BACKGROUND: Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare primary malignant tumor. Due to poor understanding of its biologic behaviors, pathological features, image manifestations and clinical effects, clinical study is urgent. Analysis of clinical data of pulmonary LCNEC, in order to improve the clinical diagnosis and treatment. METHODS: Retrospective analysis of 22 pulmonary LCNEC cases of clinical features, diagnosis, treatments and prognosis. RESULTS: Pulmonary large cell neuroendocrine carcinoma occurs in older men with heavy smoking history., clinical symptoms are cough, sputum, hemoptysis, and chest pain. Computed tomography (CT) features are peripheral mass mainly, accompanied by heterogeneous density and necrosis. Immunohistochemical neuroendocrine differentiation markers Syn, CgA and CD56 positive expression rates were: 72.7%, 68.2% and 68.2%, respectively. 17 patients underwent surgical treatment, 10 patients received adjuvant therapy, 5 underwent palliative chemotherapy. Univariate analysis indicated that smoking index (P=0.029), lymph node metastasis (P=0.034), tumor-node-metastasis (TNM) stage (P=0.005), treatment (P=0.047), postoperative chemotherapy (P=0.014) are prognostic factors. Multivariate analysis showed that lymph node metastasis (P=0.045) and postoperative chemotherapy (P=0.024) are prognostic factors. CONCLUSIONS: Pulmonary LCNEC is lack of specific clinical symptoms, and its pathological diagnosis depends on postoperative specimens, poor efficacy of various treatments is its current situation. Lymph node metastasis and postoperative chemotherapy are important prognostic factors. PMID- 26903162 TI - [Expression and Clinical Significance of MAGE-C2 in Lung Adenocarcinoma]. AB - BACKGROUND: The aim of this study is to detect the expression of melanoma antigen C2 (MAGE-C2) in lung adenocarcinoma tissues and adjacent non-cancerousous tissues and analyze its clinical significance. METHODS: The expression level of MAGE-C2 mRNA and MAGE-C2 protein were measured in 87 cases of lung adenocarcinoma tissues and adjacent non-cancerous tissues were detected by Real-time fluorescence quantitative PCR and Western blot. RESULTS: Over-expression of the MAGE-C2 mRNA and MAGE-C2 protein were observed in lung adenocarcinoma tissues (53/87, 60.9%), but nor in adjacent non-cancerous tissues. The expressions of MAGE-C2 mRNA and MAGE-C2 protein were closely associated with clinical stage, metastasis and differentiation (P<0.05). The expression rate of MAGE-C2 mRNA had no relationship with gender, age, smoking (P>0.05). The expression of MAGE-C2 had an adverse effect on overall survival rate (P<0.05). CONCLUSIONS: Over-expression of the MAGE-C2 mRNA and protein is existed in lung adenocarcinoma. The high expression of MAGE-C2 may be closely related to the occurrence and development in lung adenocarcinoma. MAGE-C2 may predict a poor prognosis and could be as a novel lung adenocarcinoma molecule marker.?. PMID- 26903163 TI - [Research Progress of PR Domain Zinc Finger Protein 14]. AB - PR domain zinc finger protein 14 (PRDM14) is an important member of the PRDM family, PRDM14 plays a key role in the maintenance of cell integrity and differentiation, growth and apoptosis of the cell. It also plays an critical role in the formation of primordial germ cells, the maintenance of the totipotency of stem cells and the formation of tissues and organs. PRDM14 bears a single PR domain and six tandemly repeated zinc fingers, which is involved in the process of the deacetylation and methylation of the histone, and is involved in the formation of tumor trough the change level of methylation in the promoter region. The abnormal methylation of PRDM14 can change the chromatin structure, DNA conformation and the interaction mode of DNA and protein, it can suppress transcription and expression of the gene, which caused the occurrence, development and metastasis of tumor. The research progress of PRDM14 is reviewed based on the relevant literatures published in China and abroad. PMID- 26903164 TI - [Development of New Molecular EZH2 on Lung Cancer Invasion and Metastasis]. AB - Lung cancer is a serious threat to human health malignancies upward trend in morbidity and mortality. It is hot topic to investigate the molecular mechanisms of lung cancer development and explore the new therapeutic targets. The underlying mechanism of EZH2 on lung cancer development will demonstrate the new pathway of lung cancer development, invasion and metastasis. The exploration and application of new targeted molecular will improve the survival rate and living quality of lung cancer patients in future. PMID- 26903165 TI - [Overview of Clinical Progress in Pulmonary Ground-glass Nodules]. AB - Ground-glass nodules (GGNs) was a special type of pulmonary nodules. With the progress of high resolution CT (HRCT), it achieved a higher positive rate and attracted much attention in recent years. For lacking characteristic symptoms, the early diagnosis of lung cancer was difficult even nowadays. However, it had been proved that GGNs was well associated with lung cancer in previous studies. Therefore, optimized managements of GGNs could help diagnosis and treatments of lung cancer at early stage. In this review, we summarized the definition, classification, imaging characteristics, growing history, molecular pathological features and suggested managements of GGNs. PMID- 26903167 TI - New Senior Editor Announcement. PMID- 26903166 TI - [Progress of Long Non-coding RNAs in Non-small Cell Lung Cancer]. AB - Lung cancer related death is the most common cause of cancer death worldwide. Non coding RNA has no protein coding capacity, but can play roles in a variety of biology. Long non-coding RNA (lncRNA) is at least 200 nt long. A variety of lncRNAs could promote or inhibit tumor development and progression in many tumors, including non-small cell lung cancer (NSCLC). Due to their fundamental role in regulating gene expression, they involve in biological mechanism of the tumor, and so they are expected to be new cancer biomarkers. In this review, we emphasized the roles of lncRNAs in NSCLC, and discuss them as diagnostic and prognostic markers and as therapeutic targets. PMID- 26903168 TI - Beyond Rare-Variant Association Testing: Pinpointing Rare Causal Variants in Case Control Sequencing Study. AB - Rare-variant association testing usually requires some method of aggregation. The next important step is to pinpoint individual rare causal variants among a large number of variants within a genetic region. Recently Ionita-Laza et al. propose a backward elimination (BE) procedure that can identify individual causal variants among the many variants in a gene. The BE procedure removes a variant if excluding this variant can lead to a smaller P-value for the BURDEN test (referred to as "BE-BURDEN") or the SKAT test (referred to as "BE-SKAT"). We here use the adaptive combination of P-values (ADA) method to pinpoint causal variants. Unlike most gene-based association tests, the ADA statistic is built upon per-site P-values of individual variants. It is straightforward to select important variants given the optimal P-value truncation threshold found by ADA. We performed comprehensive simulations to compare ADA with BE-SKAT and BE-BURDEN. Ranking these three approaches according to positive predictive values (PPVs), the percentage of truly causal variants among the total selected variants, we found ADA > BE-SKAT > BE-BURDEN across all simulation scenarios. We therefore recommend using ADA to pinpoint plausible rare causal variants in a gene. PMID- 26903169 TI - Monitoring air pollution at Mohammedia (Morocco): Pb, Cd and Zn in the blood of pigeons (Columba livia). AB - The concentrations of Pb, Cd and Zn were investigated in the blood of pigeons (Columba livia) in order to assess the degree of pollution by heavy metal. For this, wild city pigeons were caught at four different locations in Mohammedia classified according to their industrial activity and road traffic density. Significant difference in heavy metal concentrations were observed between sites studied, the highest lead and cadmium levels were found in industrial area and center town, while the highest zinc level was found in the less contaminated area. These results indicate that the industrial activities and the road traffic are the most important source of pollution. PMID- 26903170 TI - The relationship between new media exposure and fast food consumption among Chinese children and adolescents in school: a rural-urban comparison. AB - BACKGROUND: In recent decades, China has experienced an exponential growth in the number of internet users, especially among the youngest population, as well as a rapid proliferation of Western-type fast food restaurants. The health consequences of internet availability and fast food consumption among youth have been largely studied in Western countries, but few studies have focused on China. OBJECTIVES: This paper has two goals. The first is to evaluate the differences in new media exposure and preferences for fast foods between rural and urban areas. The second goal is to test the association between new media exposure and fast food consumption. The targets of this analysis are Chinese children and adolescents aged 6-18 attending school at the time of the interview. METHODS: Research hypotheses were tested using mean-groups comparisons for differences between rural urban sub-samples, and logistic regressions with odds ratios to estimate the relationship between media exposure and preferences towards fast foods. Cross-sectional data from the 2009 China Health and Nutrition Survey were employed. RESULTS: Watching online videos and playing computer games are behaviors associated with higher probabilities of eating at fast food restaurants in both rural and urban young residents, with higher odds in rural areas. Surfing the internet is associated with higher odds of being overweight in both rural and urban settings. Results also show that children living in rural areas spend significantly more time playing computer games, watching TV and videotapes, but less time doing homework than their urban peers. CONCLUSIONS: This paper suggests that monitoring the nutritional effects of new media exposure in China is of key importance in order to develop adequate health promotion policies, in both rural and urban areas. PMID- 26903171 TI - The prospective IQ-CSRC trial: A prototype early clinical proarrhythmia assessment investigation for replacing the ICH E14 thorough QTc (TQT) study. AB - INTRODUCTION: Early clinical Phase I ECG investigations designed to replace the currently applied thorough QT (TQT) study are reviewed to examine how they could complement and verify the conclusions of nonclinical investigations and, in particular, the Comprehensive in vitro Proarrhythmia Assay (CiPA). TOPICS: The IQ CSRC trial is a prospective ascending multiple-dose first in human (FIH) type investigation performed as a possible replacement for the thorough QT study (TQT). Designed in accordance with the results of a simulation study by the FDA QT Interdisciplinary Review Team (IRT), it succeeded in correctly categorizing 5/5 established QTc-prolonging agents free of notable heart rate effects (dofetilide, dolasetron, moxifloxacin, ondansetron, and quinine) and the QTc negative drug, levocetirizine. DISCUSSION: The positive results obtained with the IQ-CSRC study require additional confirmation with threshold QTc-positive and negative drugs and established QTc prolongers producing both increases and decreases in heart rate. In the future, similar studies should also adopt and validate innovative proarrhythmic metrics, in addition to, or instead of, the traditional proarrhythmic surrogate of QTc, to assess the proarrhythmic safety of candidate drugs. PMID- 26903172 TI - Positive Expectations Regarding Aging Linked to More New Friends in Later Life. AB - Objectives: Negative perceptions of aging can be self-fulfilling prophecies, predicting worse cognitive and physical outcomes. Although older adults are portrayed as either lonely curmudgeons or perfect grandparents, little research addresses how perceptions of aging relate to social outcomes. We considered whether more positive expectations about aging encourage older adults to maintain or bolster their social network connections and support. Method: This study examined baseline, 12-, and 24-month questionnaire data from the Baltimore Experience Corps Trial, a longitudinal randomized volunteer intervention for adults aged 60 years and older. The associations between expectations regarding aging and different types of social support were tested using negative binomial and multiple regression models controlling for relevant covariates such as baseline levels of perceived support availability. Results: Participants with more positive expectations at baseline made more new friends 2 years later and had greater overall perceived support availability 12 months later. Notably, only participants with at least average perceived support availability at baseline showed an association between expectations and later support availability. Discussion: These results are the first to link overall expectations regarding aging to the social domain and suggest that the influence of perceptions of aging is not limited to physical or cognitive function. PMID- 26903173 TI - SOIL GAS RADON MEASUREMENT AROUND FAULT LINES ON THE WESTERN SECTION OF THE NORTH ANATOLIAN FAULT ZONE IN TURKEY. AB - Soil gas radon activity measurements were made around the western section of the North Anatolian Fault Zone. In the study, the variation of radon concentration at 12 different locations along the fault line was monitored by using LR-115 (solid state nuclear track detectors) detectors for 12-monthly periods. Twelve radon stations were determined in the study region, and in each station, LR-115 films were installed in the borehole of ~50 cm. The recorded radon concentration varies from 29 to 7059 Bqm-3 with an average value of 1930 Bqm-3. The influence of meteorological parameters such as temperature, pressure, total rainfall and humidity on soil radon concentrations in the study area was also investigated. The positive and poor correlation was observed between average value of 222Rn concentration and temperature. There is a reverse proportion between radon level with other meteorological factors (humidity, pressure and rainfall). The results show that the measured soil gas radon activity concentration shows seasonal variation in a highly permeable sandy-gravelly soil with definite seasons without obvious long transitional periods. The summer (from June 2013 to September 2013) is characterised by 1.8 times higher average soil gas radon activity concentration (median is 2.372 kBqm-3) than the winter (from December 2012 to March 2013) (median is 1.298 kBqm-3). PMID- 26903174 TI - The effectiveness of nasal surgery on psychological symptoms in patients with obstructive sleep apnea and nasal obstruction. AB - Conclusion Nasal obstruction can aggravate the psychological status of OSA patients, and nasal surgery should reduce this aggravation. Nasal surgery significantly improved sleep latency and ameliorated several polysomnographic characteristics. Background The aim of this study was to investigate the psychological status of patients with obstructive sleep apnea (OSA) and nasal obstruction and to evaluate the effects of nasal surgery on the psychological symptoms and polysomnographic (PSG) parameters of these patients. Methods The study was designed as a prospective comparative study. This study compared 30 patients (all male) with nasal obstruction and 30 matched patients without nasal obstruction using the Pittsburgh Sleep Quality Index (PSQI) and the Symptom Check List 90 (SCL-90). All of the patients had been previously diagnosed with OSA (apnea hypopnea index [AHI] >= 5 events/h) via a whole-night polysomnographic examination. Nasal obstruction was assessed using a visual analogue scale (VAS). The patients with nasal obstruction underwent nasal surgery, and their weight, VAS, nocturnal PSG characteristics, and psychological symptoms at baseline and 3 months after surgery were compared. Results The OSA patients with nasal obstruction suffered from significantly longer sleep latency on the PSQI and higher somatization and anxiety scores on the SCL-90 than the subjects without nasal obstruction (p < 0.05). The nasal obstruction symptoms significantly improved after surgery (VAS decreased from 6.18 +/- 1.85 to 1.87 +/- 1.76, p < 0.01). The assessments also showed a significant reduction in weight (from 84.60 +/- 11.30 kg to 82.27 +/- 9.87 kg, p < 0.05) between the pre-operative and post operative values. Although there was significant reduction in the AHI (from 49.67 +/- 19.49/h to 43.07 +/- 21.86/h, p < 0.01) and a significant improvement in lowest oxygen saturation (LSpO2, from 73.83 +/- 8.49% to 75.97 +/- 9.86%, p < 0.05), only 23.3% of patients achieved a response of nasal surgery that met Sher's criteria. Remarkable reductions were observed in the sleep latency scores, daytime dysfunction scores on the PSQI, anxiety and hostility scores, and the number of positive symptoms on the SCL-90 (p < 0.05). There was a strong positive correlation between PSQI total score and some psychosomatic symptoms on the SCL 90, including inter-personal sensitivity, depression, hostility, paranoid ideation, psychoticism, global symptom index, and the number of positive symptoms (r > 0.3, p < 0.05). PMID- 26903175 TI - A common mechanism involving the TORC1 pathway can lead to amphotericin B persistence in biofilm and planktonic Saccharomyces cerevisiae populations. AB - Fungal infections are an increasing clinical problem. Decreased treatment effectiveness is associated with biofilm formation and drug recalcitrance is thought to be biofilm specific. However, no systematic investigations have tested whether resistance mechanisms are shared between biofilm and planktonic populations. We performed multiplexed barcode sequencing (Bar-seq) screening of a pooled collection of gene-deletion mutants cultivated as biofilm and planktonic cells. Screening for resistance to the ergosterol-targeting fungicide amphotericin B (AmB) revealed that the two growth modes had significant overlap in AmB-persistent mutants. Mutants defective in sterol metabolism, ribosome biosynthesis, and the TORC1 and Ras pathways showed increased persistence when treated with AmB. The ras1, ras2 and tor1 mutants had a high-persister phenotype similar to wild-type biofilm and planktonic cells exposed to the TORC1 pathway inhibitor rapamycin. Inhibition of TORC1 with rapamycin also increased the proportion of persisters in Candida albicans and Candida glabrata. We propose that decreased TORC1-mediated induction of ribosome biosynthesis via Ras can lead to formation of AmB-persister cells regardless of whether the cells are in planktonic or biofilm growth mode. Identification of common pathways leading to growth mode-independent persister formation is important for developing novel strategies for treating fungal infections. PMID- 26903177 TI - The surgical treatment of a melanoma patient with macroscopic metastasis in peri and retrocaval lymph nodes and with a positive sentinel lymph node in the groin. AB - BACKGROUND: The extension of iliac-obturator dissection in melanoma patient with metastatic sentinel node of the groin is very debated. More recent studies - in accord with guidelines for urogenital cancers - suggest the extension to pelvic lymph nodes. At present, however, anatomical limits and indications to pelvic dissection are not defined in melanoma patients with metastatic lymph nodes of groin. CASE REPORT: A 46-year-old man affected by nodular cutaneous melanoma (Breslow-thickness 10 mm, Clark-level V) on the anterior-medial surface of the right leg underwent sentinel node biopsy of groin. Three macro-metastatic sentinel lymph nodes were removed in right inguinal field and, after 2 weeks, an ipsi-lateral inguinal lymphadenectomy with an extended pelvic dissection was performed. During the surgery, we reported the presence of macrometastases also in retro/peri caval lymph nodes. As a result of these findings, we decided to perform the super-extended pelvic lymphadenectomy. Overall we removed 56 lymph nodes with 9 peri-caval and 2 retro-caval macro metastatic lymph nodes. After a period of 49 months, the patients came to our attention with multiple scrotal metastases. The imagining restaging of the patient was already negative for other melanoma localizations. DISCUSSION: Currently there are no guidelines about indications and anatomical limits of iliac-obturator extension in melanoma patients. The extended pelvic dissection is the gold-standard procedure used in urogenital carcinomas. In case of finding of macro-metastases during the surgical procedure, the approach to follow is even more uncertain. We perform a super extended pelvic dissection with a good prognosis for the patient. KEY WORDS: Caval-metastasis, Extended-pelvic-lymphadenectomy, Metastatic-melanoma. PMID- 26903178 TI - Eye and skin disorders: Part II: Ocular signs that help in diagnosis of systemic diseases in dermatology practice. PMID- 26903176 TI - Effectiveness of Short Message Service Text-Based Smoking Cessation Intervention Among University Students: A Randomized Clinical Trial. AB - IMPORTANCE: Smoking is globally the most important preventable cause of ill health and death. Mobile telephone interventions and, in particular, short message service (SMS) text messaging, have the potential to overcome access barriers to traditional health services, not least among young people. OBJECTIVE: To determine the effectiveness of a text-based smoking cessation intervention among young people. DESIGN, SETTING, AND PARTICIPANTS: A single-blind, 2-arm, randomized clinical trial (Nicotine Exit [NEXit]) was conducted from October 23, 2014, to April 17, 2015; data analysis was performed from April 23, 2014, to May 22, 2015. Participants included daily or weekly smokers willing to set a quit date within 1 month of enrollment. The study used email to invite all college and university students throughout Sweden to participate. INTERVENTIONS: The NEXit core program is initiated with a 1- to 4-week motivational phase during which participants can choose to set a stop date. The intervention group then received 157 text messages based on components of effective smoking cessation interventions for 12 weeks. The control group received 1 text every 2 weeks thanking them for participating in the study, with delayed access to the intervention. MAIN OUTCOMES AND MEASURES: The primary outcomes were self-reported prolonged abstinence (not having smoked >5 cigarettes over the past 8 weeks) and 4-week point prevalence of complete smoking cessation shortly after the completion of the intervention (approximately 4 months after the quit date). RESULTS: A total of 1590 participants, mainly between 21 and 30 years of age, were randomized into the study; 827 (573 [69.3%] women) were allocated to the intervention group and 763 (522 [68.4%] women) were included in the control group. Primary outcome data were available for 783 (94.7%) of the intervention group and 719 (94.2%) of the control group. At baseline, participants were smoking a median (range) of 63 (1-238) and 70 (2-280) cigarettes per week, respectively. Eight-week prolonged abstinence was reported by 203 participants (25.9%) in the intervention group and 105 (14.6%) in the control group; 4-week point prevalence of complete cessation was reported by 161 (20.6%) and 102 (14.2%) participants, respectively, a mean (SD) of 3.9 (0.37) months after the quit date. The adjusted odds ratios (95% CIs) for these findings were 2.05 (1.57 2.67) and 1.56 (1.19-2.05), respectively. CONCLUSIONS AND RELEVANCE: With the limitation of assessing only the short-term effect of the intervention, the effects observed in this trial are comparable with those for traditional smoking cessation interventions. The simple NEXit intervention has the potential to improve the uptake of effective smoking cessation interventions. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN75766527. PMID- 26903179 TI - Ocular manifestations of infectious skin diseases. AB - Ocular complications of infectious skin diseases are a common occurrence. Managing the inflamed or infected eye in the emergency setting presents a diagnostic and therapeutic challenge to the emergency physician. Infectious agents may affect any part of the eye. Ocular findings may be the first sign of many infectious diseases, such as, for example, gonorrhea or chlamydia infection. Understanding the various forms of ocular involvement in these conditions is important, because untreated ophthalmic involvement can lead to severe vision loss. This review focuses on the significant ocular manifestations of the most common infectious diseases, including bacterial, viral, fungal, and parasitic infections, that both ophthalmologists and dermatologists may encounter. PMID- 26903180 TI - Ocular changes induced by drugs commonly used in dermatology. AB - The use of many drugs in dermatologic diseases may cause ocular side effects. Some may regress after discontinuation of the therapy, but others persist or progress even after the cessation of treatment. This review presents four groups of commonly prescribed drugs-antimalarial medicines, glucocorticoids, retinoids, and psoralens + ultraviolet A (UVA) therapy-and discusses their possible ocular side effects. The most significant complication of antimalarial drugs is retinopathy with the risk of permanent visual impairment. There are different recommendations for screening for this drug-related retinopathy. The most important ocular manifestations of steroid management are irreversible optic nerve damage in "steroid responders" (steroid glaucoma) and cataract. Some other side effects may disappear after discontinuation of the therapy. Retinoid-induced ocular side effects include ocular surface disease as well as retinal dysfunction. It is recommended to modify the therapy when night blindness occurs or after the decrease of color vision. Protective eyewear is sufficient to avoid ocular surface problems during psoralen + UVA therapy. The knowledge of screening schemes and closer cooperation between physicians may decrease the risk of serious or irreversible ocular side effects. PMID- 26903181 TI - Ocular involvement in cutaneous connective tissue disease. AB - Connective tissue disorders commonly involve multiple organ systems including the skin and eye. The pathogenesis of many of these disorders affects the microvasculature in these organs. Redness, dryness, pain, and vision loss might be signs of ocular disease in a patient with connective tissue disease. Ocular involvement can potentially lead to blindness and indicate systemic involvement. Dermatologists should be aware of potential ocular involvement in cutaneous connective tissue disorders, and their recognition should prompt ophthalmologic evaluation. PMID- 26903182 TI - Ocular rosacea, psoriasis, and lichen planus. AB - Although the number of dermatologic conditions with ocular manifestations is relatively limited, these entities have a high prevalence and represent a large proportion of clinic visits to both dermatologic and ophthalmic practices. This contribution will review oculocutaneous diseases that are not part of the allergic or autoantibody-mediated spectrum. PMID- 26903183 TI - The eye and the skin in endocrine metabolic diseases. AB - The eye and skin may offer critical clues to the diagnosis of a varied spectrum of metabolic diseases from endocrine origin and their different stages of severity, such as diabetes mellitus and Graves disease. On the other hand, such entities may compromise the eye and visual function severely, and awareness of these possible associations is an important step in their diagnosis and management. A large number of less common endocrine diseases may also have significant ocular/visual or skin involvement. Often the etiologic relationship between the endocrine metabolic disease and the ocular compromise is unknown, but diverse pathogenetic mechanisms may act through a common pathologic pathway producing ocular damage, as occur in diabetic retinopathy. This review emphasizes the ocular and skin manifestations of different metabolic diseases of endocrine origin. PMID- 26903184 TI - The eye and the skin in nonendocrine metabolic disorders. AB - As metabolism is controlled by the input of genes and the environment, metabolic disorders result from some disturbance in the interaction between genes and environmental factors. Many metabolic disorders consist in congenital enzyme deficiencies, also known as "inborn errors of metabolism," that may be disabling or cause severe illness and death and are predominantly inherited in an autosomal recessive fashion. The deposit in cells and tissues of storage substances from errors in metabolic processes may produce a wide variety of disorders affecting different organs and functions, with different degrees of severity, and often present around the time of birth or early childhood. Distinctive ocular and skin manifestations accompany many metabolic diseases and may provide clues for their diagnosis and evolution. PMID- 26903185 TI - Cutaneous and ocular manifestations of neurocutaneous syndromes. AB - Neurocutaneous syndromes are a heterogeneous group of congenital and hereditary disorders with manifestations in the skin and the nervous system, usually together with ocular features that represent diagnostic clues and potential sources of morbidity. Dermatologists and ophthalmologists often need to work together in identifying and managing patients with these conditions; herein, we focus on classic and under-recognized neurocutaneous syndromes. We begin with autosomal dominant genodermatoses characterized by hamartomas and tumors in the skin, eyes, and central nervous system: neurofibromatosis type 1, tuberous sclerosis complex, and PTEN hamartoma-tumor syndrome. This is followed by a discussion of two mosaic disorders, Sturge-Weber syndrome and neurocutaneous melanocytosis. In addition to providing an update on clinical presentations and evaluation of patients with these conditions, we review recent insights into their pathogenesis, drawing attention to relationships among the diseases on a molecular level and implications regarding treatment. We also highlight the major features of other neurocutaneous syndromes that have ocular findings plus pigmentary, vascular, hyperkeratotic, adnexal, connective tissue, photosensitive, and inflammatory manifestations in the skin. PMID- 26903186 TI - Autoimmune bullous diseases with skin and eye involvement: Cicatricial pemphigoid, pemphigus vulgaris, and pemphigus paraneoplastica. AB - Autoimmune blistering diseases are a heterogeneous group of disorders that mostly affect the skin and mucous membranes. Occasionally, other organ systems may be involved, depending on the unique pathophysiology of each disease. Cicatricial pemphigoid, pemphigus vulgaris, and paraneoplastic pemphigus are distinct entities, but all have the potential to have cutaneous and ocular involvement. Awareness and early recognition of ocular involvement in these diseases is important given the increased risk for vision loss and blindness with delay in management. Several skin diseases may be associated with involvement of the external eye. The most common autoimmune diseases are cicatricial pemphigoid, pemphigus vulgaris, and paraneoplastic pemphigus. PMID- 26903187 TI - Multisystem diseases affecting the skin and eye. AB - There exist a wide variety of multisystem diseases that can affect both the eyes and skin. The skin and eyes may be the initial sites affected, leading to a new diagnosis of a systemic illness, or severe skin and eye involvement can drive treatment for patients with multisystem disease. It is important for physicians to be aware of how to recognize and diagnose these conditions, to evaluate patients for extent of disease, and to initiate appropriate therapies to combat these potentially severe diseases. This contribution will discuss the following diseases with a special emphasis on the mucocutaneous and ophthalmologic manifestations: reactive arthritis, sarcoidosis, necrobiotic xanthogranuloma and other granulomatous diseases, amyloidosis, Behcet disease, cholesterol emboli, Vogt-Koyanagi-Harada syndrome, and the primary vasculitides. In each case, a thorough understanding of the cutaneous manifestations and ocular manifestations are critical to help guide appropriate evaluation of these patients, and managing the ocular and cutaneous manifestations are critical to prevent morbidity and potentially devastating long-term sequelae. PMID- 26903188 TI - Ocular manifestations of genetic skin disorders. AB - Genetic skin diseases, or genodermatoses, often have extracutaneous manifestations. Ocular manifestations in particular can have significant clinical implications, like blindness. Other manifestations, such as the corneal opacities that occur in X-linked ichthyosis, are asymptomatic but characteristic of a particular genodermatosis. Ophthalmologic examination can aid in diagnosis when characteristic findings are seen. The genodermatoses with ocular manifestations will be reviewed, but neurocutaneous, syndromes, genetic pigmentary disorders, and genetic metabolic diseases are not included because they are covered elsewhere in this issue. PMID- 26903190 TI - Complications of decorative tattoo. AB - Decorative tattoo is a popular practice that is generally safe when performed in the professional setting but can be associated with a variety of inflammatory, infectious, and neoplastic complications, risks that may be increased with current trends in home tattooing. Modern tattoo inks contain azo dyes and are often of unknown composition and not currently regulated for content or purity. Biopsy of most (if not all) tattoo reactions presenting to the dermatologist is recommended, given recent clusters of nontuberculous mycobacterial infections occurring within tattoo, as well as associations between tattoo reactions and systemic diseases such as sarcoidosis. PMID- 26903189 TI - An eye on nutrition: The role of vitamins, essential fatty acids, and antioxidants in age-related macular degeneration, dry eye syndrome, and cataract. AB - Visual impairment is a global epidemic. In developing countries, nutritional deficiency and cataracts continue to be the leading cause of blindness, whereas age-related macular degeneration (AMD) and cataracts are the leading causes in developed nations. The World Health Organization has instituted VISION 2020: "The Right to Sight" as a global mission to put an end to worldwide blindness. In industrialized societies, patients, physicians, researchers, nutritionists, and biochemists have been looking toward vitamins and nutrients to prevent AMD, cataracts, and dry eye syndrome (DES). Nutrients from the AREDS2 study (lutein, zeaxanthin, vitamin C, vitamin E, zinc, copper, eicosapentanoic acid [EPA], and docosahexanoic acid [DHA]) set forth by the National Institutes of Health remain the most proven nutritional therapy for reducing the rate of advanced AMD. Omega 3 fatty acids, especially DHA, have been found to improve DES in randomized clinical trials. Conflicting results have been seen with regard to multivitamin supplementation on the prevention of cataract. PMID- 26903191 TI - The fate of Hungarian Jewish dermatologists during the Holocaust Part 1: Six refugees who fled. AB - From the times of Moritz Kaposi, Hungarian Jewish physicians have significantly contributed to the development of dermatology. Part 1 of this special report highlights some of the early Jewish dermatologists in Hungary. It also tells the stories of five Hungarian Jewish dermatologists who fled anti-Semitism in Hungary, or other European countries, between 1920 and 1941: Frederick Reiss, Emery Kocsard, Stephen Rothman, Peter Flesch, and George Csonka. A sixth Hungarian dermatologist, Tibor Benedek, was persecuted by the Nazis, because he had a Jewish wife, forcing the couple to flee Germany. Part 2 will focus on the ordeal faced by Hungarian Jewish dermatologists who did not leave their homeland during World War II. PMID- 26903192 TI - Atopic dermatitis in the domestic dog. AB - Dogs may develop a syndrome of spontaneous, inflammatory, pruritic dermatitis that shares many features with human atopic dermatitis, including a young age of onset, characteristic lesion distribution, immunoglobulin E sensitization to common environmental allergen sources, and evidence of epidermal barrier dysfunction. There are also several important differences between canine and human atopic dermatitis. Although dogs may suffer from multiple-organ hypersensitivity syndromes, there is no evidence that this species experiences the progressive evolution from cutaneous to respiratory allergy characteristic of the human atopic march. Despite the presence of epidermal barrier derangement, there is no significant association between canine atopic dermatitis and mutations in filaggrin. Finally, treatment of canine disease relies much less heavily on topical therapy than does its human counterpart, while allergy testing and allergen-specific immunotherapy provide an often essential component of effective clinical management of affected dogs. PMID- 26903193 TI - Advanced Image Acquisition and Analytical Techniques for Studies of Living Cells and Tissue Sections. AB - Studies on fixed samples or genome-wide analyses of nuclear processes are useful for generating snapshots of a cell population at a particular time point. However, these experimental approaches do not provide information at the single cell level. Genome-wide studies cannot assess variability between individual cells that are cultured in vitro or originate from different pathological stages. Immunohistochemistry and immunofluorescence are fundamental experimental approaches in clinical laboratories and are also widely used in basic research. However, the fixation procedure may generate artifacts and prevents monitoring of the dynamics of nuclear processes. Therefore, live-cell imaging is critical for studying the kinetics of basic nuclear events, such as DNA replication, transcription, splicing, and DNA repair. This review is focused on the advanced microscopy analyses of the cells, with a particular focus on live cells. We note some methodological innovations and new options for microscope systems that can also be used to study tissue sections. Cornerstone methods for the biophysical research of living cells, such as fluorescence recovery after photobleaching and fluorescence resonance energy transfer, are also discussed, as are studies on the effects of radiation at the individual cellular level. PMID- 26903194 TI - IL-1 receptor antagonist (IL-1Ra)-Fc ameliorate autoimmune arthritis by regulation of the Th17 cells/Treg balance and arthrogenic cytokine activation. AB - INTRODUCTION: IL-1beta signalling has a critical role in the pathogenesis of various types of inflammatory arthritis including rheumatoid arthritis (RA). We aimed to investigate the therapeutic effects of human IL-1 receptor antagonist with Fc fragment (hIL-1Ra-Fc) on autoimmune arthritis and to identify the possible mechanisms by which hIL-1RA-Fc exerts anti-arthritic effects in a murine model of RA and patients with rheumatoid arthritis. METHODS: Collagen-induced arthritis (CIA) murine model was established in DBA/1J mice. The levels of various cytokines were determined by using enzyme-linked immunosorbent assay. The mouse joints were assessed for clinical arthritis score and histologic features. Th17 cells and Treg cells were stained by using antibodies specific for CD4, IL 17, CD25, and FoxP3. Osteoclastogenesis was determined by TRAP staining and real time PCR. RESULTS: hIL-1RA-Fc reduced the arthritis incidence, histological inflammation and cartilage score in the CIA model. The expression of proinflammatory cytokines, VEGF and RANK, was reduced in the affected joint of hIL-1Ra-Fc-treated mice. hIL-1Ra-Fc-treated mice showed decreased number of Th17 cells with increased number of Treg cells in spleens. hIL-1Ra-Fc reduced Th17 cell differentiation by inactivation of STAT3 signalling, and reciprocally induced Treg cell differentiation through STAT5 signalling. In addition, the expression of IL-17, TNF-alpha, RANKL, and VEGF was decreased, while Foxp3 gene expression was increased in PBMCs of RA patients after administration of hIL-1Ra Fc. CONCLUSION: The anti-arthritis effects of hIL-1RA-Fc are associated with regulation of balance between Th17 cells and Treg cells and suppression of osteoclastogenesis and angiogenesis in the affected joints. PMID- 26903195 TI - The new insight into management of hepatitis B virus patients with flare. PMID- 26903198 TI - The design of an optical triode. AB - Under the action of pump light, a conventional photonic crystal can be turned into a functional photonic crystal. In the paper, we have designed an optical triode with a one-dimensional functional photonic crystal, and analyzed the effect of period number, medium thickness, refractive index, incident angle, the irradiation frequency and the intensity of the pump light on the optical triode magnification. We obtain some valuable results, which shall help to optimize the design of optical triodes. PMID- 26903197 TI - Intraoperative Dexmedetomidine Promotes Postoperative Analgesia and Recovery in Patients after Abdominal Hysterectomy: a Double-Blind, Randomized Clinical Trial. AB - Surgery-induced acute postoperative pain and stress response can lead to prolonged convalescence. The present study was designed to investigate the effects of intraoperative dexmedetomidine on postoperative analgesia and recovery following abdominal hysterectomy surgeries. Sixty-four patients scheduled for abdominal hysterectomy under general anesthesia were divided into two groups that were maintained using propofol/remifentanil/dexmedetomidine (PRD) or propofol/remifentanil/saline (PRS). During surgery, patients in the PRD group had a lower bispectral index (BIS) value, which indicated a deeper anesthetic state, and a higher sedation score immediately after extubation than patients in the PRS group. During the first 24 hours post-surgery, PRD patients consumed less morphine with patient-controlled analgesia (PCA) and had lower scores on a visual analogue scale (VAS) than their controls from the PRS group. The global 40-item quality of recovery questionnaire and 9-question fatigue severity score both showed higher recovery scores from day 3 after surgery in the PRD group. with the data are considered together, intraoperative administration of dexmedetomidine appeared to promote the analgesic properties of morphine-based PCA and to expedite recovery following surgery in patients undergoing abdominal hysterectomy. PMID- 26903196 TI - Discovery of 12-mer peptides that bind to wood lignin. AB - Lignin, an abundant terrestrial polymer, is the only large-volume renewable feedstock composed of an aromatic skeleton. Lignin has been used mostly as an energy source during paper production; however, recent interest in replacing fossil fuels with renewable resources has highlighted its potential value in providing aromatic chemicals. Highly selective degradation of lignin is pivotal for industrial production of paper, biofuels, chemicals, and materials. However, few studies have examined natural and synthetic molecular components recognizing the heterogeneous aromatic polymer. Here, we report the first identification of lignin-binding peptides possessing characteristic sequences using a phage display technique. The consensus sequence HFPSP was found in several lignin-binding peptides, and the outer amino acid sequence affected the binding affinity of the peptides. Substitution of phenylalanine7 with Ile in the lignin-binding peptide C416 (HFPSPIFQRHSH) decreased the affinity of the peptide for softwood lignin without changing its affinity for hardwood lignin, indicating that C416 recognised structural differences between the lignins. Circular dichroism spectroscopy demonstrated that this peptide adopted a highly flexible random coil structure, allowing key residues to be appropriately arranged in relation to the binding site in lignin. These results provide a useful platform for designing synthetic and biological catalysts selectively bind to lignin. PMID- 26903199 TI - A replaceable liposomal aptamer for the ultrasensitive and rapid detection of biotin. AB - Biotin is an essential vitamin which plays an important role for maintaining normal physiological function. A rapid, sensitive, and simple method is necessary to monitor the biotin level. Here, we reported a replacement assay for the detection of biotin using a replaceable liposomal aptamer. Replacement assay is a competitive assay where a sample analyte replaces the labeled competitor of analyte out of its biorecognition element on a surface. It is user friendly and time-saving because of washing free. We used aptamer as a competitor, not a biorecognition element as tradition. To label aptamers, we used cholesterol conjugated aptamers to tag signal-amplifying-liposomes. Without the need of conjugation procedure, aptamers can be easily incorporated into the surface of dye-encapsulating liposomes. Two aptamers as competitors of biotin, ST-21 and ST 21M with different affinities to streptavidin, were studied in parallel for the detection of biotin using replacement assays. ST-21 and ST-21M aptamers reached to limits of detection of 1.32 pg/80 MUl and 0.47 pg/80 MUl, respectively. The dynamic ranges of our assays using ST-21 and ST-21M aptamers were seven and four orders of magnitude, respectively. This assay can be completed in 20 minutes without washing steps. These results were overall better than previous reported assays. PMID- 26903201 TI - The Influence of Chemokine CXCR4 and Cyclooxygenase-2 in the Recurrence of Pterygium. AB - PURPOSE: To investigate the role of CXCR4 and cyclooxygenase-2 in pterygium recurrence. METHODS: A total of 18 primary and 9 recurrent pterygium samples were analyzed. Immunohistochemical staining using primary antibodies against cyclooxygenase-2 and CXCR4 was performed. The cyclooxygenase-2 and CXCR4 expressing cells were calculated separately on the epithelium and stroma. In addition, a correlation between the area of pterygium and CXCR4 and cyclooxygenase-2 levels was investigated. RESULTS: In the primary pterygium group, cyclooxygenase-2 staining was more intense in the epithelium and more dominant in the stroma of the recurrence samples. The CXCR4 expression was more intense in the stroma of both groups. The highest CXCR4 expression was observed in the recurrent pterygium group. There was a strong correlation between the area of pterygium and CXCR4 and cyclooxygenase-2 of stroma. CONCLUSIONS: CXCR4 and cyclooxygenase-2 may play an important role in the recurrence of pterygium. PMID- 26903200 TI - Epigenetically mediated spontaneous reduction of NFAT1 expression causes imbalanced metabolic activities of articular chondrocytes in aged mice. AB - OBJECTIVE: Abnormal metabolic activities of chondrocytes may cause articular cartilage (AC) degradation, but key transcription factors regulating metabolic activities in AC of aging individuals remain unknown. This study aimed to investigate the role of transcription factor NFAT1 in regulating the expression of anabolic and catabolic molecules in AC of aged mice. METHODS: The hip, knee, and shoulder joints of BALB/c mice were harvested at 6, 12, 15, 18, and 24 months of age for histopathological and immunohistochemical (IHC) analyses. Total RNA was isolated from AC for gene expression. Genomic DNA and chromatin were prepared from AC for methylated DNA immunoprecipitation (MeDIP) and chromatin immunoprecipitation (ChIP) assays. RESULTS: NFAT1 expression in AC of mice was significantly decreased after 12 months of age, which was associated with reduced proteoglycan staining, decreased expression of chondrocyte markers, and increased expression of interleukin-1beta. Forced Nfat1 expression in chondrocytes from aged mice significantly reversed the abnormal metabolic activities. ChIP assays confirmed that NFAT1 bound to the promoter of the Acan, Col2a1, Col9a1, Col11a1, Il1b, Mmp13 and Tnfa genes in articular chondrocytes of aged mice. ChIP and MeDIP assays revealed that reduced NFAT1 expression in AC of aged mice was regulated by epigenetic histone methylation at the promoter region and was correlated with increased DNA methylation at introns 1 and 10 of the Nfat1 gene. CONCLUSION: NFAT1 is a transcriptional regulator of multiple anabolic and catabolic genes in AC of aged mice. Epigenetically mediated reduction of NFAT1 expression causes imbalanced metabolic activities of articular chondrocytes in aged mice. PMID- 26903203 TI - Evolutionary dynamics of a smoothed war of attrition game. AB - In evolutionary game theory the War of Attrition game is intended to model animal contests which are decided by non-aggressive behavior, such as the length of time that a participant will persist in the contest. The classical War of Attrition game assumes that no errors are made in the implementation of an animal's strategy. However, it is inevitable in reality that such errors must sometimes occur. Here we introduce an extension of the classical War of Attrition game which includes the effect of errors in the implementation of an individual's strategy. This extension of the classical game has the important feature that the payoff is continuous, and as a consequence admits evolutionary behavior that is fundamentally different from that possible in the original game. We study the evolutionary dynamics of this new game in well-mixed populations both analytically using adaptive dynamics and through individual-based simulations, and show that there are a variety of possible outcomes, including simple monomorphic or dimorphic configurations which are evolutionarily stable and cannot occur in the classical War of Attrition game. In addition, we study the evolutionary dynamics of this extended game in a variety of spatially and socially structured populations, as represented by different complex network topologies, and show that similar outcomes can also occur in these situations. PMID- 26903202 TI - The role of microRNAs in metal carcinogen-induced cell malignant transformation and tumorigenesis. AB - MicroRNAs (miRNAs), an important component of epigenetic mechanisms of carcinogenesis, have been shown to play crucial roles in cancer initiation, metastasis, prognosis and responses to drug treatment and may serve as biomarkers for early diagnosis of cancer and tools for cancer therapy. Metal carcinogens, such as arsenic, cadmium, hexavalent chromium and nickel, are well-established human carcinogens causing various cancers upon long term exposure. However, the mechanism of metal carcinogenesis has not been well understood, which limits our capability to effectively diagnose and treat human cancers resulting from chronic metal carcinogen exposure. Over recent years, the role of miRNAs in metal carcinogenesis has been actively explored and a growing body of evidence indicates the critical involvement of miRNAs in metal carcinogenesis. This review aims to discuss recent studies showing that miRNAs play important roles in metal carcinogen-induced cell malignant transformation and tumorigenesis. Some thoughts for future further studies in this field are also presented. PMID- 26903204 TI - Bacterial gliding fluid dynamics on a layer of non-Newtonian slime: Perturbation and numerical study. AB - Gliding bacteria are an assorted group of rod-shaped prokaryotes that adhere to and glide on certain layers of ooze slime attached to a substratum. Due to the absence of organelles of motility, such as flagella, the gliding motion is caused by the waves moving down the outer surface of these rod-shaped cells. In the present study we employ an undulating surface model to investigate the motility of bacteria on a layer of non-Newtonian slime. The rheological behavior of the slime is characterized by an appropriate constitutive equation, namely the Carreau model. Employing the balances of mass and momentum conservation, the hydrodynamic undulating surface model is transformed into a fourth-order nonlinear differential equation in terms of a stream function under the long wavelength assumption. A perturbation approach is adopted to obtain closed form expressions for stream function, pressure rise per wavelength, forces generated by the organism and power required for propulsion. A numerical technique based on an implicit finite difference scheme is also employed to investigate various features of the model for large values of the rheological parameters of the slime. Verification of the numerical solutions is achieved with a variational finite element method (FEM). The computations demonstrate that the speed of the glider decreases as the rheology of the slime changes from shear-thinning (pseudo plastic) to shear-thickening (dilatant). Moreover, the viscoelastic nature of the slime tends to increase the swimming speed for the shear-thinning case. The fluid flow in the pumping (generated where the organism is not free to move but instead generates a net fluid flow beneath it) is also investigated in detail. The study is relevant to marine anti-bacterial fouling and medical hygiene biophysics. PMID- 26903205 TI - Cognitive Decline in Presymptomatic Alzheimer Disease. PMID- 26903206 TI - Voluntary fortification of breakfast cereals with folic acid: contribution to dietary intake in Australia. AB - Ready-to-eat breakfast cereals have been voluntarily fortified with folic acid since 1995, with the purpose of reducing the prevalence of neural tube defects in utero. Using data from the recent Australian Health Survey, this study aimed to estimate folate intake from one serving of breakfast cereals (median amount). Various commercial brands were purchased in 2002 (n = 19) and in 2014 (n = 14); folate was determined by microbiological assay and high-pressure liquid chromatography (HPLC). Total folate (MUg/100 g) in 2002 and 2014 selections were 144-633 and 147-564, respectively, and mostly comparable to nutrition labels. Folic acid (2014 selection) using HPLC, ranged from 85 to 411 MUg/100 g. Intake of 51 g cereals/serving by individuals >= 2 years could contribute 75-288 MUg dietary folate equivalent. It seems that folic acid intake among children (2-3 years) exceeds the recommended dietary intake, when certain brands of breakfast cereals are consumed. Accordingly, the benefits and potential detrimental effects of the voluntary fortification need to be further explored. PMID- 26903207 TI - Absolute Quantification of Enterococcal 23S rRNA Gene Using Digital PCR. AB - We evaluated the ability of chip-based digital PCR (dPCR) to quantify enterococci, the fecal indicator recommended by the United States Environmental Protection Agency (USEPA) for water-quality monitoring. dPCR uses Poisson statistics to estimate the number of DNA fragments in a sample with a specific sequence. Underestimation may occur when a gene is redundantly encoded in the genome and multiple copies of that gene are on one DNA fragment. When genomic DNA (gDNA) was extracted using two commercial DNA extraction kits, we confirmed that dPCR could discern individual copies of the redundant 23s rRNA gene in the enterococcal genome. dPCR quantification was accurate when compared to the nominal concentration inferred from fluorometer measurements (linear regression slope = 0.98, intercept = 0.03, R(2) = 0.99, and p value <0.0001). dPCR quantification was also consistent with quantitative PCR (qPCR) measurements as well as cell counts for BioBall reference standard and 24 environmental water samples. qPCR and dPCR quantification of enterococci in the 24 environmental samples were significantly correlated (linear regression slope =1.08, R(2) of 0.96, and p value <0.0001); the group mean of the qPCR measurements was 0.19 log units higher than that of the dPCR measurements. At environmentally relevant concentrations, dPCR quantification was more precise (i.e., had narrower 95% confidence intervals than qPCR quantification). We observed that humic acid caused a similar level of inhibition in both dPCR and qPCR, but calcium inhibited dPCR to a lesser degree than qPCR. Inhibition of dPCR was partially relieved when the number of thermal cycles was increased. Based on these results, we conclude that dPCR is a viable option for enumerating enterococci in ambient water. PMID- 26903208 TI - Statistical power to detect change in a mangrove shoreline fish community adjacent to a nuclear power plant. AB - An expansion is underway of a nuclear power plant on the shoreline of Biscayne Bay, Florida, USA. While the precise effects of its construction and operation are unknown, impacts on surrounding marine habitats and biota are considered by experts to be likely. The objective of the present study was to determine the adequacy of an ongoing monitoring survey of fish communities associated with mangrove habitats directly adjacent to the power plant to detect fish community changes, should they occur, at three spatial scales. Using seasonally resolved data recorded during 532 fish surveys over an 8-year period, power analyses were performed for four mangrove fish metrics (fish diversity, fish density, and the occurrence of two ecologically important fish species: gray snapper (Lutjanus griseus) and goldspotted killifish (Floridichthys carpio). Results indicated that the monitoring program at current sampling intensity allows for detection of <33% changes in fish density and diversity metrics in both the wet and the dry season in the two larger study areas. Sampling effort was found to be insufficient in either season to detect changes at this level (<33%) in species-specific occurrence metrics for the two fish species examined. The option of supplementing ongoing, biological monitoring programs for improved, focused change detection deserves consideration from both ecological and cost-benefit perspectives. PMID- 26903210 TI - Sex-Specific Research: A Key Component in Improving Prognosis After Transcatheter Aortic Valve Replacement. PMID- 26903209 TI - Massive land system changes impact water quality of the Jhelum River in Kashmir Himalaya. AB - The pristine aquatic ecosystems in the Himalayas are facing an ever increasing threat from various anthropogenic pressures which necessitate better understanding of the spatial and temporal variability of pollutants, their sources, and possible remedies. This study demonstrates the multi-disciplinary approach utilizing the multivariate statistical techniques, data from remote sensing, lab, and field-based observations for assessing the impact of massive land system changes on water quality of the river Jhelum. Land system changes over a period of 38 years have been quantified using multi-spectral satellite data to delineate the extent of different anthropogenically driven land use types that are the main non-point sources of pollution. Fifteen water quality parameters, at 12 sampling sites distributed uniformly along the length of the Jhelum, have been assessed to identify the possible sources of pollution. Our analysis indicated that 18% of the forested area has degraded into sparse forest or scrublands from 1972 to 2010, and the areas under croplands have decreased by 24% as people shifted from irrigation-intensive agriculture to orchard farming while as settlements showed a 397% increase during the observation period. One way ANOVA revealed that all the water quality parameters had significant spatio temporal differences (p < 0.01). Cluster analysis (CA) helped us to classify all the sampling sites into three groups. Factor analysis revealed that 91.84% of the total variance was mainly explained by five factors. Drastic changes in water quality of the Jhelum since the past three decades are manifested by increases in nitrate-nitrogen, TDS, and electric conductivity. The especially high levels of nitrogen (858 +/- 405 MUgL(-1)) and phosphorus (273 +/- 18 MUgL(-1)) in the Jhelum could be attributed to the reckless application of fertilizers, pesticides, and unplanned urbanization in the area. PMID- 26903211 TI - Peripheral membrane proteins: Tying the knot between experiment and computation. AB - Experimental biology has contributed to answer questions about the morphology of a system and how molecules organize themselves to maintain a healthy functional cell. Single-molecule techniques, optical and magnetic experiments, and fluorescence microscopy have come a long way to probe structural and dynamical information at multiple scales. However, some details are simply too small or the processes are too short-lived to detect by experiments. Computational biology provides a bridge to understand experimental results at the molecular level, makes predictions that have not been seen in vivo, and motivates new fields of research. This review focuses on the advances on peripheral membrane proteins (PMPs) studies; what is known about their interaction with membranes, their role in cell biology, and some limitations that both experiment and computation still have to overcome to gain better structural and functional understanding of these PMPs. As many recent reviews have acknowledged, interdisciplinary efforts between experiment and computation are needed in order to have useful models that lead future directions in the study of PMPs. We present new results of a case study on a PMP that behaves as an intricate machine controlling lipid homeostasis between cellular organelles, Osh4 in yeast Saccharomyces cerevisiae. Molecular dynamics simulations were run to examine the interaction between the protein and membrane models that reflect the lipid diversity of the endoplasmic reticulum and trans Golgi membranes. Our study is consistent with experimental data showing several residues that interact to smaller or larger extent with the bilayer upon stable binding (~200 ns into the trajectory). We identified PHE239 as a key residue stabilizing the protein-membrane interaction along with two other binding regions, the ALPS-like motif and the beta6-beta7 loops in the mouth region of the protein. This article is part of a Special Issue entitled: Membrane Proteins edited by J.C. Gumbart and Sergei Noskov. PMID- 26903212 TI - Maternal Weaning Modulates Emotional Behavior and Regulates the Gut-Brain Axis. AB - Evidence shows that nutritional and environmental stress stimuli during postnatal period influence brain development and interactions between gut and brain. In this study we show that in rats, prevention of weaning from maternal milk results in depressive-like behavior, which is accompanied by changes in the gut bacteria and host metabolism. Depressive-like behavior was studied using the forced-swim test on postnatal day (PND) 25 in rats either weaned on PND 21, or left with their mother until PND 25 (non-weaned). Non-weaned rats showed an increased immobility time consistent with a depressive phenotype. Fluorescence in situ hybridization showed non-weaned rats to harbor significantly lowered Clostridium histolyticum bacterial groups but exhibit marked stress-induced increases. Metabonomic analysis of urine from these animals revealed significant differences in the metabolic profiles, with biochemical phenotypes indicative of depression in the non-weaned animals. In addition, non-weaned rats showed resistance to stress-induced modulation of oxytocin receptors in amygdala nuclei, which is indicative of passive stress-coping mechanism. We conclude that delaying weaning results in alterations to the gut microbiota and global metabolic profiles which may contribute to a depressive phenotype and raise the issue that mood disorders at early developmental ages may reflect interplay between mammalian host and resident bacteria. PMID- 26903213 TI - The Use of Sonographically Guided Botulinum Toxin Type A (Dysport) Injections Into the Tensor Fasciae Latae for the Treatment of Lateral Patellofemoral Overload Syndrome. AB - BACKGROUND: Pain in the anterior and lateral parts of the knee during exercise is a common clinical problem for which current management strategies are often unsuccessful. PURPOSE: To investigate the effect of an ultrasound-guided botulinum toxin (BT) injection into the tensor fasciae latae (TFL), followed by physical therapy, in patients classified with lateral patellofemoral overload syndrome (LPOS) who failed to respond to conventional treatment. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A total of 45 patients (mean +/- SD age, 32.4 +/- 8.6 years) who met the inclusion criteria of (1) activity-related anterolateral knee symptoms, (2) symptoms lasting longer than 3 months, (3) a pathological abnormality confirmed by magnetic resonance imaging, and (4) previous failed physical therapy received an ultrasound-guided injection of BT into the TFL followed by physical therapy. Patient-reported outcomes were collected at 5 intervals: before the injection; at 1, 4, and 12 weeks after the injection; and at a mean 5 years after the injection. In 42 patients, relative iliotibial band (ITB) length changes were assessed using the modified Ober test at the first 4 time points. A computational model was run to simulate the effect of TFL weakening on gluteus medius (GMed) activity. Statistical analysis was undertaken using 1-way analysis of variance and paired t tests with Bonferroni post hoc correction. RESULTS: There was a significant improvement in Anterior Knee Pain Scale scores from before the injection (61 +/- 15) to 1 (67 +/- 15), 4 (70 +/- 16), and 12 weeks (76 +/- 16) after the injection and in 87% of patients (39/45 patients available for follow-up) at approximately 5 years (from 62.9 +/- 15.4 to 87.0 +/- 12.5) after the injection (all P < .010). A significant effect on the modified Ober test was identified as a result of the intervention, with an increase in leg drop found at 1 (3 degrees +/- 5 degrees ), 4 (4 degrees +/- 5 degrees ), and 12 (7 degrees +/- 6 degrees ) weeks after the injection compared with before the injection (all P < .010). Simulating a progressive reduction in TFL strength resulted in corresponding increases in GMed activity during gait. CONCLUSION: An injection of BT into the TFL, combined with physical therapy, resulted in a significant improvement of symptoms in patients with LPOS, which was maintained at 5-year follow-up. This may result from reduced lateral TFL/ITB tension or to an increase in GMed activity in response to inhibition of the TFL. PMID- 26903214 TI - Effects of Pulsed Electromagnetic Fields on Return to Sports After Arthroscopic Debridement and Microfracture of Osteochondral Talar Defects: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial. AB - BACKGROUND: Osteochondral defects (OCDs) of the talus usually affect athletic patients. The primary surgical treatment consists of arthroscopic debridement and microfracture. Various possibilities have been suggested to improve the recovery process after debridement and microfracture. A potential solution to obtain this goal is the application of pulsed electromagnetic fields (PEMFs), which stimulate the repair process of bone and cartilage. HYPOTHESIS: The use of PEMFs after arthroscopic debridement and microfracture of an OCD of the talus leads to earlier resumption of sports and an increased number of patients that resume sports. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: A total of 68 patients were randomized to receive either PEMFs (n = 36) or placebo (n = 32) after arthroscopic treatment of an OCD of the talus. The primary outcomes (ie, the number of patients who resumed sports and time to resumption of sports) were analyzed with Kaplan-Meier curves as well as Mann-Whitney U, chi square, and log-rank tests. Secondary functional outcomes were assessed with questionnaires (American Orthopaedic Foot and Ankle Society ankle-hindfoot score, Foot and Ankle Outcome Score, EuroQol, and numeric rating scales for pain and satisfaction) at multiple time points up to 1-year follow-up. To assess bone repair, computed tomography scans were obtained at 2 weeks and 1 year postoperatively. RESULTS: Almost all outcome measures improved significantly in both groups. The percentage of sport resumption (PEMF, 79%; placebo, 80%; P = .95) and median time to sport resumption (PEMF, 17 weeks; placebo, 16 weeks; P = .69) did not differ significantly between the treatment groups. Likewise, there were no significant between-group differences with regard to the secondary functional outcomes and the computed tomography results. CONCLUSION: PEMF does not lead to a higher percentage of patients who resume sports or to earlier resumption of sports after arthroscopic debridement and microfracture of talar OCDs. Furthermore, no differences were found in bone repair between groups. REGISTRATION: Netherlands Trial Register NTR1636. PMID- 26903215 TI - The Effect of the Mulligan Knee Taping Technique on Patellofemoral Pain and Lower Limb Biomechanics. AB - BACKGROUND: Patellofemoral pain (PFP) affects 25% of the general population, occurring 2 times more often in females compared with males. Taping is a valuable component of the management plan for altering lower limb biomechanics and providing pain relief; however, the effects of alternative taping techniques, such as Mulligan knee taping, appear yet to be researched. PURPOSE: To determine whether the Mulligan knee taping technique altered levels of perceived knee pain and lower limb biomechanics during a single-legged squat (SLSq) in adult females with PFP. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 20 female patients with PFP, aged 18 to 35 years, participated in this study. Participants performed 3 to 5 SLSq on their most symptomatic limb during a taped (Mulligan knee taping technique) and nontaped (control) condition. During the eccentric phase of the SLSq, the 3-dimensional kinematics (250 Hz) of the knee and hip and the ground-reaction forces (1000 Hz) and muscle activation patterns (1000 Hz) of the gluteus medius, vastus lateralis, and vastus medialis oblique were measured. Participants' perceived maximum knee pain was also recorded after the completion of each squat. RESULTS: Between-condition differences were found for hip kinematics and gluteus medius activation but not for kinetics or vastus medialis oblique and vastus lateralis muscle activity (timing and activation). Compared with the nontaped condition, the Mulligan knee taping technique significantly (P = .001) reduced perceived pain during the SLSq (mean +/- SD: 2.29 +/- 1.79 and 1.29 +/- 1.28, respectively). In the taped condition compared with the control, the onset timing of the gluteus medius occurred significantly earlier (120.6 +/- 113.0 and 156.6 +/- 91.6 ms, respectively; P = .023) and peak hip internal rotation was significantly reduced (6.38 degrees +/- 7.31 degrees and 8.34 degrees +/- 7.92 degrees , respectively; P = .002). CONCLUSION: The Mulligan knee taping technique successfully reduced knee pain in participants with PFP. This is the first study to establish a link between Mulligan knee taping and the reduction of PFP in conjunction with decreased hip internal rotation and earlier activation of gluteus medius. CLINICAL RELEVANCE: The Mulligan knee taping technique may benefit the clinical environment by providing an alternative evidence-based treatment plan for PFP. PMID- 26903216 TI - Symptomatic Heterotopic Ossification After Ulnar Collateral Ligament Reconstruction: Clinical Significance and Treatment Outcome. AB - BACKGROUND: Ulnar collateral ligament (UCL) reconstruction is an increasingly common procedure being performed in overhead throwing athletes. Recently, postoperative imaging has revealed the presence of heterotopic ossification (HO) in symptomatic patients. PURPOSE: To determine the incidence of symptomatic HO after UCL reconstruction as well as the clinical outcomes after nonoperative or operative treatment of HO. STUDY DESIGN: Case series, Level of evidence, 4. METHODS: A search was performed of diagnostic codes for all UCL reconstructions at a single institution between 2002 and 2012, and the charts were then reviewed of patients who returned to clinic for symptomatic HO after UCL reconstruction. All relevant clinical information, imaging findings, and return-to-play data were obtained. RESULTS: Eight patients were found to have developed symptomatic HO after UCL reconstruction. Of the 8 patients, 6 had gracilis tendon autograft at their primary surgery. All 8 patients had HO on the proximal end of their graft. Two patients were treated nonoperatively, and the remainder had excision of HO performed either arthroscopically or open. Six patients were able to return to the same or higher level of competition after treatment of HO. CONCLUSION: Symptomatic HO after UCL reconstruction is very uncommon but may prove to be a significant complication among athletes. With appropriate treatment, the majority of patients were able to return to the same level of play. Early identification of this complication is important, as revision surgery with excision of osteophytes resulted in a return to a similar level of play in most patients. PMID- 26903217 TI - Synthesis of Enantiopure T-Symmetrical [6:0]-Hexakis Adducts of C60 Equipped with 1,2-Glycol Substituted cyclo-Monomalonate Addends. AB - The synthesis of T-symmetrical [6:0]-hexakis adducts of C60 bearing enantiopure cyclo-monomalonate addends equipped with 1,2-glycol groups masked as isopropylidene acetals is presented. The deprotection of the acetals afforded functional fullerene building blocks bearing six 1,2-glycol moieties in an octahedral geometry as connection sites with appropriate linear organic spacers targeting 3D chiral extended networks with cubic building units. Evaluation of the experimental results revealed the advantageous synthetic accessibility to hexakis adduct (-)-9 which carries six homochiral C12 cyclo-monomalonate addends. PMID- 26903218 TI - Alternative packing of EGFR transmembrane domain suggests that protein-lipid interactions underlie signal conduction across membrane. AB - The human epidermal growth factor receptor (EGFR) of HER/ErbB receptor tyrosine kinase family mediates a broad spectrum of cellular responses transducing biochemical signals via lateral dimerization in plasma membrane, while inactive receptors can exist in both monomeric and dimeric forms. Recently, the dimeric conformation of the helical single-span transmembrane domains of HER/ErbB employing the relatively polar N-terminal motifs in a fashion permitting proper kinase activation was experimentally determined. Here we describe the EGFR transmembrane domain dimerization via an alternative weakly polar C-terminal motif A(661)xxxG(665) presumably corresponding to the inactive receptor state. During association, the EGFR transmembrane helices undergo a structural adjustment with adaptation of inter-molecular polar and hydrophobic interactions depending upon the surrounding membrane properties that directly affect the transmembrane helix packing. This might imply that signal transduction through membrane and allosteric regulation are inclusively mediated by coupled protein protein and protein-lipid interactions, elucidating paradoxically loose linkage between ligand binding and kinase activation. PMID- 26903219 TI - Substitutions mimicking deimination and phosphorylation of 18.5-kDa myelin basic protein exert local structural effects that subtly influence its global folding. AB - Intrinsically-disordered proteins (IDPs) present a complex interplay of conformational variability and multifunctionality, modulated by environment and post-translational modifications. The 18.5-kDa myelin basic protein (MBP) is essential to the formation of the myelin sheath of the central nervous system and is exemplary in this regard. We have recently demonstrated that the unmodified MBP-C1 component undergoes co-operative global conformational changes in increasing concentrations of trifluoroethanol, emulating the decreasing dielectric environment that the protein encounters upon adsorption to the oligodendrocyte membrane [K.A. Vassall et al., Journal of Molecular Biology, 427, 1977-1992, 2015]. Here, we extended this study to the pseudo-deiminated MBP-C8 charge component, one found in greater proportion in developing myelin and in multiple sclerosis. A similar tri-conformational distribution as for MBP-C1 was observed with slight differences in Gibbs free energy. A more dramatic difference was observed by cathepsin D digestion of the protein in both aqueous and membrane environments, which showed significantly greater accessibility of the F42-F43 cut site of MBP-C8, indicative of a global conformational change. In contrast, this modification caused little change in the protein's density of packing on myelin mimetic membranes as ascertained by double electron-electron resonance spectroscopy [D.R. Kattnig et al., Biochimica et Biophysica Acta (Biomembranes), 1818, 2636-2647, 2012], or in its affinity for Ca(2+)-CaM. Site-specific threonyl pseudo-phosphorylation at residues T92 and/or T95 did not appreciably affect any of the thermodynamic mechanisms of conformational transitions, susceptibility to cathepsin D, or affinity for Ca(2+)-CaM, despite previously having been shown to affect local structure and disposition on the membrane surface. PMID- 26903220 TI - Binding of cationic peptides (KX)4K to DPPG bilayers. Increasing the hydrophobicity of the uncharged amino acid X drives formation of membrane bound beta-sheets: A DSC and FT-IR study. AB - The binding of cationic peptides of the sequence (KX)4K to lipid vesicles of negatively charged dipalmitoyl-phosphatidylglycerol (DPPG) was investigated by differential scanning calorimetry (DSC) and temperature dependent Fourier transformed infrared (FT-IR) spectroscopy. The hydrophobicity of the uncharged amino acid X was changed from G (glycine) over A (alanine), Abu (alpha aminobutyric acid), V (valine) to L (leucine). The binding of the peptides caused an increase of the phase transition temperature (Tm) of DPPG by up to 20 degrees C. The shift depended on the charge ratio and on the hydrophobicity of the amino acid X. Unexpectedly, the upward shift of Tm increased with increasing hydrophobicity of X. FT-IR spectroscopy showed a shift of the CH2 stretching vibrations of DPPG to lower frequency, particularly for bilayers in the liquid crystalline phase, indicating an ordering of the hydrocarbon chains when the peptides were bound. Changes in the lipid C=O vibrational band indicated a dehydration of the lipid headgroup region after peptide binding. (KG)4K was bound in an unordered structure at all temperatures. All other peptides formed intermolecular antiparallel beta-sheets, when bound to gel phase DPPG. However, for (KA)4K and (KAbu)4K, the beta-sheets converted into an unordered structure above Tm. In contrast, the beta-sheet structures of (KV)4K and (KL)4K remained stable even at 80 degrees C when bound to the liquid-crystalline phase of DPPG. Strong aggregation of DPPG vesicles occurred after peptide binding. For the aggregates, we suggest a structure, where aggregated single beta-sheets are sandwiched between opposing DPPG bilayers with a dehydrated interfacial region. PMID- 26903221 TI - Functional roles of MICU1 and MICU2 in mitochondrial Ca(2+) uptake. AB - MICU1 and MICU2 are the main regulators of the mitochondrial Ca(2+)-uniporter (MCU), but their precise functional role is still under debate. We show here that MICU2 behaves as a pure inhibitor of MCU at low cytosolic [Ca(2+)] ([Ca(2+)]c), though its effects decrease as [Ca(2+)]c is increased and disappear above 7 MUM. Regarding MICU1, studying its effects is more difficult because knockdown of MICU1 leads also to loss of MICU2. However, while knockdown of MICU2 induces only a persistent increase in mitochondrial Ca(2+) uptake, knockdown of MICU1 also induces a peculiar use-dependent transient activation of MCU that cannot be attributed to the parallel loss of MICU2. Therefore, MICU1 is endowed with a specific inhibitory effect on MCU at low [Ca(2+)]c, separate and kinetically different from that of MICU2. On the other hand, we and others have shown previously that MICU1 activates MCU at [Ca(2+)]c above 2.5 MUM. Thus, MICU1 has a double role in MCU regulation, inhibitory at low [Ca(2+)]c and activatory at high [Ca(2+)]c. PMID- 26903223 TI - The Evaluation of Diabetic Macular Ischemia Using Optical Coherence Tomography Angiography. AB - PURPOSE: The purpose of this study was to compare optical coherence tomography (OCT) angiography to standard fluorescein angiography (FA) in the grading of diabetic macular ischemia. METHODS: In our study, OCT angiography and traditional FA images were acquired from 24 diabetic patients. The level of diabetic macular ischemia in the superficial capillary plexus was graded with standard Early Treatment Diabetic Retinopathy Study (ETDRS) protocols and a comparison between conventional FA and OCT angiography was performed. The deep vascular plexus and choriocapillaris were also graded for macular ischemia. Additionally, flow indices were analyzed for all OCT angiography images. RESULTS: We identified moderate agreement between diabetic macular ischemia grades for conventional FA and OCT angiography (weighted kappa of 0.53 and 0.41). In addition, the intergrader agreement for the superficial, deep, and choriocapillaris scores was substantial (weighted kappa of 0.65, 0.61, and 0.65, respectively). Finally, the parafoveal flow indices were shown to have a statistically significant relationship with diabetic macular ischemia grades for the superficial capillary plexus (P = 0.04) and choriocapillaris (P = 0.036), with a trend toward significance for the deep capillary plexus (P = 0.13). CONCLUSIONS: We demonstrated moderate agreement between diabetic macular ischemia grading results for OCT angiography and conventional FA using standard ETDRS protocols. We also showed that OCT angiography images could be graded for diabetic macular ischemia with substantial intergrader agreement. PMID- 26903226 TI - Hypothermia Promotes Survival of Ischemic Retinal Ganglion Cells. AB - PURPOSE: Ischemic stroke in retinal arteries leads to death of neural tissue and ultimately to blindness. The retina is known to die within 4 hours after onset of ischemia. It is debated whether hypothermia might increase the time window for medical treatment and thereby the chance of recovering sight. In order to characterize the time course of cell death during ischemia and potential beneficial effects of hypothermia in more detail, we investigated the survival of ganglion cells in ischemic pig and human retina as a function of time and temperature. METHODS: Eyes were obtained from minipigs and from human donors post mortem. Enucleated minipig eyes were stored for defined durations at three different temperatures (37 degrees C, 21 degrees C, and 4 degrees C). In order to assess the viability of the tissue, we measured ganglion cell activity (spiking) with multielectrode arrays. RESULTS: Minipig retinal ganglion cell function was severely compromised after 2 hours of ischemia at body temperature. After 4 hours, ganglion cells did not fire action potentials anymore. However, at 21 degrees C, ganglion cell activity was maintained under ischemic conditions for up to 12 hours, and for at least 50 hours at 4 degrees C. In postmortem human retina, we recorded ganglion cell activity in retinas received up to 27 hours after death. CONCLUSIONS: Our results demonstrate that hypothermia greatly increases survival of retinal ganglion cells exposed to ischemia. These results might be relevant for the future treatment of retinal ischemia. PMID- 26903224 TI - Two-Photon Autofluorescence Imaging Reveals Cellular Structures Throughout the Retina of the Living Primate Eye. AB - PURPOSE: Although extrinsic fluorophores can be introduced to label specific cell types in the retina, endogenous fluorophores, such as NAD(P)H, FAD, collagen, and others, are present in all retinal layers. These molecules are a potential source of optical contrast and can enable noninvasive visualization of all cellular layers. We used a two-photon fluorescence adaptive optics scanning light ophthalmoscope (TPF-AOSLO) to explore the native autofluorescence of various cell classes spanning several layers in the unlabeled retina of a living primate eye. METHODS: Three macaques were imaged on separate occasions using a custom TPF AOSLO. Two-photon fluorescence was evoked by pulsed light at 730 and 920 nm excitation wavelengths, while fluorescence emission was collected in the visible range from several retinal layers and different locations. Backscattered light was recorded simultaneously in confocal modality and images were postprocessed to remove eye motion. RESULTS: All retinal layers yielded two-photon signals and the heterogeneous distribution of fluorophores provided optical contrast. Several structural features were observed, such as autofluorescence from vessel walls, Muller cell processes in the nerve fibers, mosaics of cells in the ganglion cell and other nuclear layers of the inner retina, as well as photoreceptor and RPE layers in the outer retina. CONCLUSIONS: This in vivo survey of two-photon autofluorescence throughout the primate retina demonstrates a wider variety of structural detail in the living eye than is available through conventional imaging methods, and broadens the use of two-photon imaging of normal and diseased eyes. PMID- 26903227 TI - SyntEyes: A Higher-Order Statistical Eye Model for Healthy Eyes. AB - PURPOSE: Stochastic eye models are a method to generate random biometry data with the variability found in the general population for use in optical calculations. This work improves the accuracy of a previous model by including the higher-order shape parameters of the cornea. METHODS: The right eye biometry of 312 subjects (40.8 +/- 11.0 years of age) were measured with an autorefractometer, a Scheimpflug camera, an optical biometer, and a ray tracing aberrometer. The corneal shape parameters, exported as Zernike coefficients, were converted to eigenvectors for dimensional reduction. The remaining 18 parameters were modeled as a sum of two multivariate Gaussians, from which an unlimited number of synthetic data sets (SyntEyes) were generated. After conversion back to Zernike coefficients, the data were introduced into ray tracing software. RESULTS: The mean values of nearly all SyntEyes parameters were statistically equal to those of the original data (two one-sided t-test, P > 0.05/109, Bonferroni correction). The variability of the SyntEyes parameters was similar to the original data for most important shape parameters and intraocular distances (F-test, P < 0.05/109), but significantly lower for the higher-order shape parameters (F-test, P > 0.05/109). The same was seen for the correlations between higher-order shape parameters. After applying simulated cataract or refractive surgery to the SyntEyes model, a very close resemblance to previously published clinical outcome data was seen. CONCLUSIONS: The SyntEyes model produces synthetic biometry that closely resembles clinically measured data, including the normal biological variations in the general population. PMID- 26903225 TI - In Vivo Two-Photon Fluorescence Kinetics of Primate Rods and Cones. AB - PURPOSE: The retinoid cycle maintains vision by regenerating bleached visual pigment through metabolic events, the kinetics of which have been difficult to characterize in vivo. Two-photon fluorescence excitation has been used previously to track autofluorescence directly from retinoids and pyridines in the visual cycle in mouse and frog retinas, but the mechanisms of the retinoid cycle are not well understood in primates. METHODS: We developed a two-photon fluorescence adaptive optics scanning light ophthalmoscope dedicated to in vivo imaging in anesthetized macaques. Using pulsed light at 730 nm, two-photon fluorescence was captured from rods and cones during light and dark adaptation through the eye's pupil. RESULTS: The fluorescence from rods and cones increased with light exposure but at different rates. During dark adaptation, autofluorescence declined, with cone autofluorescence decreasing approximately 4 times faster than from rods. Rates of autofluorescence decrease in rods and cones were approximately 4 times faster than their respective rates of photopigment regeneration. Also, subsets of sparsely distributed cones were less fluorescent than their neighbors immediately following bleach at 565 nm and they were comparable with the S cone mosaic in density and distribution. CONCLUSIONS: Although other molecules could be contributing, we posit that these fluorescence changes are mediated by products of the retinoid cycle. In vivo two-photon ophthalmoscopy provides a way to monitor noninvasively stages of the retinoid cycle that were previously inaccessible in the living primate eye. This can be used to assess objectively photoreceptor function in normal and diseased retinas. PMID- 26903228 TI - Morphological Abnormalities of Schlemm's Canal in Primary Open-Angle Glaucoma From the Aspect of Aging. AB - PURPOSE: To evaluate morphological abnormalities of Schlemm's canal (SC) among primary open-angle glaucoma (POAG) patients with a family history of POAG (group A), those without a family history of POAG (group B), and patients with normal tension glaucoma (group C) from the aspect of aging. METHODS: A total of 160 trabeculectomy specimens from 133 POAG patients were processed for light microscopy using immunohistochemical staining of thrombomodulin and transmission electron microscopy. The following parameters were statistically evaluated: SC length, the percentage of the thrombomodulin-negative area (PTNA) of SC, and the inner-wall SC endothelial cell density (SC-ECD/100 MUm). RESULTS: No significant differences in age were observed among the three groups (group A: 56.71 +/- 14.83; group B: 58.13 +/- 18.13; group C: 56.61 +/- 9.78). Length of SC in the group A patients (198.70 +/- 81.65 MUm, n = 70 eyes) was significantly shorter than in group B (250.30 +/- 70.83 MUm, n = 67 eyes), and group C (277.70 +/- 65.52 MUm, n = 23 eyes) patients. A positive correlation of patient age and SC length was observed in group B (r = 0.45, P = 0.0013), but SC length in group A tended to decrease with aging (r = -0.22, P = 0.07). No significant difference in SC was found between group A and B patients before age 50 years (P = 0.30). Correlations between patient age and increase of PTNA (r = 0.38, P = 0.0013) and patient age and decrease of SC-ECD (r = -0.53, P = 3.95 * 10(-6)) were observed only in the group B cases. CONCLUSIONS: Our findings suggest that SC in group A may easily collapse during middle age, while SC in group B remains open and SC endothelial cells drop out at around middle age. PMID- 26903230 TI - Responding to Incidents of Sexual Victimization in Correctional Institutions: Correctional Officer Perspectives. AB - This study examined beliefs among correctional officers about responding to inmate-on-inmate sexual assault in jails. It is unique in its focus as no other published study has examined this topic using these variables in this setting. The authors utilize survey methodology to measure correctional officer perceptions about responding to sexual assaults among inmates. Results indicate that support for responding to instances of sexual assault among inmates differs somewhat by type of response and size of jail facility examined. Multivariate results suggest that while perceptions of inmate credibility are usually relevant, demographic factors matter more for those who work in larger jails, while beliefs about rape myths are somewhat more relevant in smaller jails. Implications for correctional policy and training and avenues for continued research are discussed. PMID- 26903229 TI - A comprehensive review of imaging findings in human cysticercosis. AB - Cysticercosis is a zoonotic disease most commonly affecting brain, eye and muscles, causing significant morbidity. Transmitted by faeco-oral route, this disease was endemic in many developing countries; it is now seen worldwide due to globalisation. Manifestations are produced by the mass effect of the parasite and by the immune response mounted by the host on the parasite. There are myriad clinical features and imaging findings. Radiological features depend on the number, stage and location of the parasite and associated complications. Knowledge of radiological findings is necessary to make an accurate diagnosis of this pleomorphic disease. PMID- 26903232 TI - Hypersensitive Transport in Photonic Crystals with Accidental Spatial Degeneracies. AB - A localized mode in a photonic layered structure can develop nodal points (nodal planes), where the oscillating electric field is negligible. Placing a thin metallic layer at such a nodal point results in the phenomenon of induced transmission. Here we demonstrate that if the nodal point is not a point of symmetry, then even a tiny alteration of the permittivity in the vicinity of the metallic layer drastically suppresses the localized mode along with the resonant transmission. This renders the layered structure highly reflective within a broad frequency range. Applications of this hypersensitive transport for optical and microwave limiting and switching are discussed. PMID- 26903231 TI - Mindfulness and Rehabilitation: Teaching Yoga and Meditation to Young Men in an Alternative to Incarceration Program. AB - This study used participant/observation and open-ended interviews to understand how male participants (age 18-24 years) benefited from yoga and mindfulness training within an Alternative to Incarceration (ATI) program. Findings suggest that the male participants (age 18-24 years) benefited from the intervention through reductions in stress and improvements in emotion regulation. Several participants noted the importance of the development of an embodied practice for assisting them in managing anger and impulse control. The young men's narratives suggest that mindfulness-based interventions can contribute positively to rehabilitative outcomes within alternative to incarcerations settings, providing complementary benefit to existing ATI programs, especially for clients amenable to mindfulness training. With many jurisdictions expanding rehabilitation-focused interventions for young offenders, service providers should consider the potential positive contributions that mindfulness-based interventions can have for fostering desistance and reducing recidivism among justice system-involved populations. PMID- 26903233 TI - Objective and Subjective Cognitive Problems among Caregivers and Matched Non caregivers. AB - Purpose of the study: Caregivers (CGs) have been shown to do more poorly than non caregivers (NCGs) on objective cognitive tests (Trails B and Digit Symbol Test, DST), but less is known about whether these groups differ in: (a) reports of subjective cognitive problems (SCPs, memory complaints, etc.) and (b) relationships of SCPs with objective cognitive tests, depression, and stress exposure. Such relationships are important because researchers/clinicians use SCPs as proxies for objective cognitive tests. Design and methods: One hundred and twenty-two spouse CGs of persons with Alzheimer's disease and 117 demographically matched NCG spouses were compared on Trails B and DST at baseline (T1), 1 year later (T2), and 2 years later (T3) and on SCPs at T1. Results: Trails B was slower in CGs than NCGs and DST declined in CGs relative to NCGs. CGs reported more SCPs than NCGs. Depression mediated group differences in Trails and DST and was also associated with SCPs. Trails B and DST explained variance in SCPs in NCGs, but not in CGs. Hours of care explained variance in SCPs in CGs, but not in NCGs. Implications: When using SCPs to make inferences about CG cognitive function, researchers/clinicians should consider the possible influence of stress exposures and depression. The lack of associations of objective and subjective cognitive measures may be a reflection of poorer self-monitoring among CGs, a potential new area of CG research. PMID- 26903235 TI - Hemodialysis in a Healthy Patient--A Case of an Erroneous Laboratory Result: A Teachable Moment. PMID- 26903236 TI - Learning needs checks. PMID- 26903234 TI - H18 Carbon: A New Metallic Phase with sp2-sp3 Hybridized Bonding Network. AB - Design and synthesis of three-dimensional metallic carbons are currently one of the hot issues in contemporary condensed matter physics because of their fascinating properties. Here, based on first-principles calculations, we discover a novel stable metallic carbon allotrope (termed H18 carbon) in () symmetry with a mixed sp(2)-sp(3) hybridized bonding network. The dynamical stability of H18 carbon is verified by phonon mode analysis and molecular dynamics simulations, and its mechanical stability is analyzed by elastic constants, bulk modulus, and shear modulus. By simulating the x-ray diffraction patterns, we propose that H18 carbon would be one of the unidentified carbon phases observed in recent detonation experiments. The analysis of the band structure and density of states reveal that this new carbon phase has a metallic feature mainly due to the C atoms with sp(2) hybridization. This novel 3D metallic carbon phase is anticipated to be useful for practical applications such as electronic and mechanical devices. PMID- 26903237 TI - Beam damage by the induced electric field in transmission electron microscopy. AB - Electric fields can be induced by electron irradiation of insulating thin film materials. In this work, the electric fields under a broad beam illumination in transmission electron microscopy (TEM) are analyzed for insulating samples. Some damage phenomena observed can be interpreted by the mechanism of damage by the induced electric field (DIEF). For broad-beam illumination in an ultra-thin specimen, the electric field near the center of the illumination may not be strong, but at the periphery of the illumination the electric field can be significant. Therefore, damage may be easily observed in these regions rather than at the center of the illumination. For a beam which is broad compared to the specimen thickness, e.g. 100~1000nm, a strong electric field pointing inward into the specimen near the surface region may result in cation diffusion into the specimen and/or anion diffusion out to the surface region. Meanwhile, a strong electric field perpendicular to the beam direction near the edge of the illumination may attract anions into the illuminated region, but eject cations to the periphery. For a wedge-shaped specimen, the electric field points inward into thicker region, driving cations toward the thicker region, while attracting anions to the edge region. On the sharp edge, a strong electric field pointing outward may be responsible for the edge-smoothing effect observed in insulating materials. PMID- 26903238 TI - Intensive Auditory Cognitive Training Improves Verbal Memory in Adolescents and Young Adults at Clinical High Risk for Psychosis. AB - OBJECTIVE: Individuals at clinical high risk (CHR) for psychosis demonstrate cognitive impairments that predict later psychotic transition and real-world functioning. Cognitive training has shown benefits in schizophrenia, but has not yet been adequately tested in the CHR population. METHODS: In this double-blind randomized controlled trial, CHR individuals (N = 83) were given laptop computers and trained at home on 40 hours of auditory processing-based exercises designed to target verbal learning and memory operations, or on computer games (CG). Participants were assessed with neurocognitive tests based on the Measurement and Treatment Research to Improve Cognition in Schizophrenia initiative (MATRICS) battery and rated on symptoms and functioning. Groups were compared before and after training using a mixed-effects model with restricted maximum likelihood estimation, given the high study attrition rate (42%). RESULTS: Participants in the targeted cognitive training group showed a significant improvement in Verbal Memory compared to CG participants (effect size = 0.61). Positive and Total symptoms improved in both groups over time. CONCLUSIONS: CHR individuals showed patterns of training-induced cognitive improvement in verbal memory consistent with prior observations in schizophrenia. This is a particularly vulnerable domain in individuals at-risk for psychosis that predicts later functioning and psychotic transition. Ongoing follow-up of this cohort will assess the durability of training effects in CHR individuals, as well as the potential impact on symptoms and functioning over time. Clinical Trials Number: NCT00655239. URL: https://clinicaltrials.gov/ct2/show/NCT00655239?term=vinogradov&rank=5. PMID- 26903239 TI - Effects of synthetic and biological disease modifying antirheumatic drugs on lipid and lipoprotein parameters in patients with rheumatoid arthritis. AB - BACKGROUND: Dyslipidemia in rheumatoid arthritis (RA) patients is frequently observed, and treatment with anti-rheumatic drugs has an impact on lipid profiles. Pathophysiologically, inflammation leads to decreased blood lipids and lipoproteins; RA treatment reduces inflammation and therefore may increase lipids and lipoproteins. Whether the lipid changes with RA treatment confer an increased risk of cardiovascular disease or just reflect their potentially atheroprotective anti-inflammatory effect is currently unclear due to limited and conflicting data. OBJECTIVE: The aim of this review is to summarize the current knowledge on the effects of synthetic and biological disease modifying antirheumatic drugs for the treatment of RA on lipid and lipoprotein parameters. RESULTS: Recent studies on methotrexate emphasize its anti-atherogenic effect. Golimumab combined with methotrexate revealed a trend towards an anti-atherogenic potential. The known pro-atherogenic lipid-spectrum alterations caused by tofacitinib can be effectively treated with atorvastatin. Tocilizumab signals a favorable impact on the extent of lipid modifications when combined with methotrexate. Abatacept indicated a trend towards an anti-atherogenic lipid profile demonstrated by favorable effects on HDL-C and on the TC/HDL-C ratio. Rituximab has beneficial effects on HDL-C and ApoA1, as well as on the ApoB/ApoA1 ratio. CLINICAL IMPLICATIONS: Anti-rheumatic drugs have various effects on lipid parameters, which in part appear pro-atherogenic. However, because many of these lipid changes may well reflect their potentially atheroprotective anti-inflammatory action the cardiovascular impact of these changes remains unclear. Whatsoever, cardiovascular safety trials for antirheumatic drugs would be valuable. PMID- 26903240 TI - Glucocorticoid-induced fetal origins of adult hypertension: Association with epigenetic events. AB - Hypertension is a predominant risk factor for cardiovascular diseases and a major health care burden. Accumulating epidemiological and experimental evidence suggest that adult-onset hypertension may have its origins during early development. Upon exposure to glucocorticoids, the fetus develops hypertension, and the offspring may be programmed to continue the hypertensive trajectory into adulthood. Elevated oxidative stress and deranged nitric oxide system are not only hallmarks of adult hypertension but are also observed earlier in life. Endothelial dysfunction and remodeling of the vasculature, which are robustly associated with increased incidence of hypertension, are likely to have been pre programmed during fetal life. Apparently, genomic, non-genomic, and epigenomic factors play a significant role in the development of hypertension, including glucocorticoid-driven effects on blood pressure. In this review, we discuss the involvement of the aforementioned participants in the pathophysiology of hypertension and suggest therapeutic opportunities for targeting epigenome modifiers, potentially for personalized medicine. PMID- 26903241 TI - Otud7b facilitates T cell activation and inflammatory responses by regulating Zap70 ubiquitination. AB - Signal transduction from the T cell receptor (TCR) is crucial for T cell-mediated immune responses and, when deregulated, also contributes to the development of autoimmunity. How TCR signaling is regulated is incompletely understood. In this study, we demonstrate a ubiquitin-dependent mechanism in which the deubiquitinase Otud7b has a crucial role in facilitating TCR signaling. Upon TCR ligation, Otud7b is rapidly recruited to the tyrosine kinase Zap70, a central mediator of TCR-proximal signaling. Otud7b deficiency attenuates the activation of Zap70 and its downstream pathways and impairs T cell activation and differentiation, rendering mice refractory to T cell-mediated autoimmune and inflammatory responses. Otud7b facilitated Zap70 activation by deubiquitinating Zap70, thus preventing the association of Zap70 with the negative-regulatory phosphatases Sts1 and Sts2. These findings establish Otud7b as a positive regulator of TCR proximal signaling and T cell activation, highlighting the importance of deubiquitination in regulating Zap70 function. PMID- 26903242 TI - Mediator facilitates transcriptional activation and dynamic long-range contacts at the IgH locus during class switch recombination. AB - Immunoglobulin (Ig) class switch recombination (CSR) is initiated by the transcription-coupled recruitment of activation-induced cytidine deaminase (AID) to Ig switch regions (S regions). During CSR, the IgH locus undergoes dynamic three-dimensional structural changes in which promoters, enhancers, and S regions are brought to close proximity. Nevertheless, little is known about the underlying mechanisms. In this study, we show that Med1 and Med12, two subunits of the mediator complex implicated in transcription initiation and long-range enhancer/promoter loop formation, are dynamically recruited to the IgH locus enhancers and the acceptor regions during CSR and that their knockdown in CH12 cells results in impaired CSR. Furthermore, we show that conditional inactivation of Med1 in B cells results in defective CSR and reduced acceptor S region transcription. Finally, we show that in B cells undergoing CSR, the dynamic long range contacts between the IgH enhancers and the acceptor regions correlate with Med1 and Med12 binding and that they happen at a reduced frequency in Med1 deficient B cells. Our results implicate the mediator complex in the mechanism of CSR and are consistent with a model in which mediator facilitates the long-range contacts between S regions and the IgH locus enhancers during CSR and their transcriptional activation. PMID- 26903245 TI - Here/In This Issue and There/Abstract Thinking: Wielding Weapons: The Intersection Between Firearms and Child Psychiatry. PMID- 26903243 TI - Leukemia-associated activating mutation of Flt3 expands dendritic cells and alters T cell responses. AB - A common genetic alteration in acute myeloid leukemia is the internal tandem duplication (ITD) in FLT3, the receptor for cytokine FLT3 ligand (FLT3L). Constitutively active FLT3-ITD promotes the expansion of transformed progenitors, but also has pleiotropic effects on hematopoiesis. We analyzed the effect of FLT3 ITD on dendritic cells (DCs), which express FLT3 and can be expanded by FLT3L administration. Pre-leukemic mice with the Flt3(ITD) knock-in allele manifested an expansion of classical DCs (cDCs) and plasmacytoid DCs. The expansion originated in DC progenitors, was cell intrinsic, and was further enhanced in Flt3(ITD/ITD) mice. The mutation caused the down-regulation of Flt3 on the surface of DCs and reduced their responsiveness to Flt3L. Both canonical Batf3 dependent CD8(+) cDCs and noncanonical CD8(+) cDCs were expanded and showed specific alterations in their expression profiles. Flt3(ITD) mice showed enhanced capacity to support T cell proliferation, including a cell-extrinsic expansion of regulatory T (T reg) cells. Accordingly, these mice restricted alloreactive T cell responses during graft-versus-host reaction, but failed to control autoimmunity without T reg cells. Thus, the FLT3-ITD mutation directly affects DC development, indirectly modulating T cell homeostasis and supporting T reg cell expansion. We hypothesize that this effect of FLT3-ITD might subvert immunosurveillance and promote leukemogenesis in a cell-extrinsic manner. PMID- 26903246 TI - Prepubescent Transgender Children: What We Do and Do Not Know. PMID- 26903244 TI - Control of Foxp3 stability through modulation of TET activity. AB - Ten-eleven translocation (TET) enzymes oxidize 5-methylcytosine (5mC) to 5 hydroxymethylcytosine and other oxidized methylcytosines, intermediates in DNA demethylation. In this study, we examine the role of TET proteins in regulating Foxp3, a transcription factor essential for the development and function of regulatory T cells (T reg cells), a distinct lineage of CD4(+) T cells that prevent autoimmunity and maintain immune homeostasis. We show that during T reg cell development in the thymus, TET proteins mediate the loss of 5mC in T reg cell-specific hypomethylated regions, including CNS1 and CNS2, intronic cis regulatory elements in the Foxp3 locus. Similar to CNS2-deficient T reg cells, the stability of Foxp3 expression is markedly compromised in T reg cells from Tet2/Tet3 double-deficient mice. Vitamin C potentiates TET activity and acts through Tet2/Tet3 to increase the stability of Foxp3 expression in TGF-beta induced T reg cells. Our data suggest that targeting TET enzymes with small molecule activators such as vitamin C might increase induced T reg cell efficacy. PMID- 26903247 TI - Sluggish Cognitive Tempo: A (Misnamed) Second Attention Disorder? PMID- 26903248 TI - Attention Finally Being Paid to Girls at Risk of Autism. PMID- 26903249 TI - Attention Bias Modification Treatment Reduces Depression Symptoms in Youth. PMID- 26903250 TI - The Internal, External, and Diagnostic Validity of Sluggish Cognitive Tempo: A Meta-Analysis and Critical Review. AB - OBJECTIVE: To conduct the first meta-analysis evaluating the internal and external validity of the sluggish cognitive tempo (SCT) construct as related to or distinct from attention-deficit/hyperactivity disorder (ADHD) and as associated with functional impairment and neuropsychological functioning. METHOD: Electronic databases were searched through September 2015 for studies examining the factor structure and/or correlates of SCT in children or adults. The search procedures identified 73 papers. The core SCT behaviors included across studies, as well as factor loadings and reliability estimates, were reviewed to evaluate internal validity. Pooled correlation effect sizes using random effects models were used to evaluate SCT in relation to external validity domains (i.e., demographics, other psychopathologies, functional impairment, and neuropsychological functioning). RESULTS: Strong support was found for the internal validity of the SCT construct. Specifically, across factor analytic studies including more than 19,000 individuals, 13 SCT items loaded consistently on an SCT factor as opposed to an ADHD factor. Findings also support the reliability (i.e., internal consistency, test-retest reliability, interrater reliability) of SCT. In terms of external validity, there is some indication that SCT may increase with age (r = 0.11) and be associated with lower socioeconomic status (r = 0.10). Modest (potentially negligible) support was found for SCT symptoms being higher in males than females in children (r = 0.05) but not in adults. SCT is more strongly associated with ADHD inattention (r = 0.63 in children, r = 0.72 in adults) than with ADHD hyperactivity-impulsivity (r = 0.32 in children, r = 0.46 in adults), and it likewise appears that SCT is more strongly associated with internalizing symptoms than with externalizing symptoms. SCT is associated with significant global, social, and academic impairment (r = 0.38-0.44). Effects for neuropsychological functioning are mixed, although there is initial support for SCT being associated with processing speed, sustained attention, and metacognitive deficits. CONCLUSION: This meta-analytic review provides strong support for the internal validity of SCT and preliminary support for the external validity of SCT. In terms of diagnostic validity, there is currently not enough evidence to describe SCT in diagnostic terms. Key directions for future research are discussed, including evaluating the conceptualization of SCT as a transdiagnostic construct and the need for longitudinal research. PMID- 26903251 TI - Prospective Longitudinal Studies of Infant Siblings of Children With Autism: Lessons Learned and Future Directions. AB - OBJECTIVE: The objectives of this review are to highlight the impact of the first decade of high-risk (HR) infant sibling work in autism spectrum disorder (ASD) and to identify potential areas of translational focus for the next decade of research. METHOD: A group of clinicians and researchers in ASD working both inside and outside of the HR design met on a regular basis to review the infant sibling research, and came to an agreement on areas that had changed clinical practice and areas that had the potential to change practice with further research. The group then outlined several methodological and translational challenges that must be addressed in the next decade of research if the field is to reach its potential. RESULTS: The review concluded that the HR design has yielded an understanding that ASD often, but not always, begins to emerge between 6 and 18 months, with early signs affecting social communication. Research using the HR design has also allowed a better understanding of the sibling recurrence risk (between 10% and 20%). Emerging areas of interest include the developmental trajectories of social communications skills in the early years, the expression of a milder phenotype in siblings not affected with ASD, and the possibility that early intervention with infant siblings may improve outcomes for those with ASD. Important challenges for the future include linking screening to intervention, collecting large sample sizes while ensuring cross-site reliability, and building in capacity for replication. CONCLUSION: Although there are significant methodological and translational challenges for high-risk infant sibling research, the potential of this design to improve long-term outcomes of all children with ASD is substantial. PMID- 26903252 TI - Enhanced Social Attention in Female Infant Siblings at Risk for Autism. AB - OBJECTIVE: Sexual dimorphism in autism spectrum disorders (ASD) is a well recognized but poorly understood phenomenon. Females are four times less likely to be diagnosed with ASD than males and, when diagnosed, are more likely to exhibit comorbid anxiety symptoms. One of the key phenotypic features of ASD is atypical attention to socially relevant stimuli. Eye-tracking studies indicate atypical patterns of spontaneous social orienting during the prodromal and early syndromic stages of ASD. However, there have been no studies evaluating sex differences in early social orienting and their potential contribution to later outcomes. METHOD: We examined sex differences in social orienting in 6-, 9-, and 12-month-old infants at high genetic risk for ASD (n = 101) and in low-risk controls (n = 61), focusing on neurobehavioral measures of function across a spectrum of autism risk. RESULTS: Results suggest that, between 6 and 12 months of age, a period highly consequential for the development of nonverbal social engagement competencies, high-risk females show enhanced attention to social targets, including faces, compared to both high-risk males and low-risk males and females. Greater attention to social targets in high-risk infants was associated with less severe social impairments at 2 years. CONCLUSION: The results suggest an alternative expression of autism risk in females, which manifests in infancy as increased attention toward socially relevant stimuli. This increased attention may serve as a female protective factor against ASD by providing increased access to social experiences in early development. PMID- 26903254 TI - Attention Bias Modification Treatment for Adolescents With Major Depression: A Randomized Controlled Trial. AB - OBJECTIVE: Attention bias modification (ABM) is a promising treatment for depression, but trial data remain restricted to adults. The present trial examined effects of ABM on adolescent depression. METHOD: A total of 45 adolescents with major depressive disorder (MDD), selected from a school population (n = 2,731) using a 2-stage case-finding procedure, were randomized to an active ABM intervention (n = 23) or placebo ABM training (n = 22). In the active condition, participants completed a neutral ABM over 2 weeks for 8 sessions (320 trials each) to shift attention away from sad words to neutral words. At a 9-week follow-up, they received a positive ABM for 2 weeks with 4 more sessions (480 trials each), shifting attention to positive words. The placebo training used the same tasks but shifted attention toward neutral and sad words equally often. Attentional biases and clinical status determined by semi structured interviews and questionnaires were obtained before and after each training. Depressive symptoms were reassessed at 8- and 12-month follow-ups. RESULTS: Greater reductions in attentional bias score and clinician-rated depressive symptoms were found for active ABM compared with placebo after initial neutral ABM. More participants no longer met diagnostic criteria for MDD in active ABM than in placebo. Greater reductions in self-reported depressive and anxious symptoms at the 12-month follow-up were also found in active ABM compared with placebo. CONCLUSION: ABM may be a potential treatment tool for mild to moderate adolescent major depression. CLINICAL TRIAL REGISTRATION INFORMATION: Attention Bias Modification Treatment for Major Depressive Disorder in Adolescents: A Randomized Controlled Trial; http://clinicaltrials.gov/; NCT02078258. PMID- 26903256 TI - Gender Differences in Associations Between Attention-Deficit/Hyperactivity Disorder and Substance Use Disorder. AB - OBJECTIVE: To examine gender differences in the association between attention deficit/hyperactivity disorder (ADHD) and substance use disorder (SUD), and to explore the impact of comorbid psychiatric conditions. METHOD: This was a cohort study of all children born in Denmark in 1990 to 2003 (n = 729,560). By record linkage across nationwide registers, we merged data on birth characteristics, socioeconomic status, familial psychiatric history, and diagnoses of ADHD (N = 19,645), comorbidities, and SUD. Hazard ratios (HR) with 95% CIs were estimated by Cox regression and adjusted for a range of variables. RESULTS: ADHD increased the risk of alcohol abuse (HRfemales = 1.72 [95% CI = 1.42-2.08], HRmales = 1.57 [1.37-1.79]), cannabis abuse (HRfemales = 2.72 [2.12-3.47], HRmales = 2.24 [1.86 2.70]), and other illicit substance abuse (HRfemales = 2.05 [1.54-2.73], HRmales = 2.42 [1.98-2.96]), compared to individuals without ADHD. In the overall estimates, no gender differences were found. Among individuals with ADHD without comorbidities, females had a higher SUD risk than males, as did females with ADHD and conduct disorder (CD). Comorbid CD, depression, bipolar disorder, and schizophrenia further increased the risk of SUD in ADHD, compared to non-ADHD. Autism spectrum disorder in males with ADHD lowered the SUD risk. CONCLUSION: ADHD increased the risk of all SUD outcomes. Individuals with ADHD without comorbidities were also at increased risk, and some comorbid disorders further increased the risk. Females and males with ADHD had comparable risks of SUD, although females had higher risk of some SUDs than males. Females with ADHD may be perceived as less impaired than males, but they are at equally increased risk of SUD. PMID- 26903253 TI - A Randomized Clinical Trial of an Integrative Group Therapy for Children With Severe Mood Dysregulation. AB - OBJECTIVE: Nonepisodic irritability is a common and impairing problem, leading to the development of the diagnoses severe mood dysregulation (SMD) and disruptive mood dysregulation disorder (DMDD). No psychosocial therapies have been formally evaluated for either, with medication being the most common treatment. This study examined the feasibility and efficacy of a joint parent-child intervention for SMD. METHOD: A total of 68 participants aged 7 to 12 years with attention deficit/hyperactivity disorder (ADHD) and SMD were randomly assigned to the 11 week therapy or community-based psychosocial treatment. All participants were first stabilized on psychostimulant medication by study physicians. Of the participants, 56 still manifested impairing SMD symptoms and entered the therapy phase. Masked evaluators assessed participants at baseline, midpoint, and endpoint, with therapy participants reassessed 6 weeks later. RESULTS: All but 2 therapy participants attended the majority of sessions (n = 29), with families reporting high levels of satisfaction. The primary outcome of change in mood symptoms using the Mood Severity Index (MSI) did not reach significance except in the subset attending the majority of sessions (effect size = 0.53). Therapy was associated with significantly greater improvement in parent-rated irritability (effect size = 0.63). Treatment effects for irritability but not MSI diminished after therapy stopped. Little impact on ADHD symptoms was seen. Results may not be generalizable to youth with SMD and comorbidities different from those seen in this sample of children with ADHD, and are limited by the lack of a gold standard for measuring change in SMD symptoms. CONCLUSION: While failing to significantly improve mood symptoms versus community treatment, the integrative therapy was found to be a feasible and efficacious treatment for irritability in participants with SMD and ADHD. CLINICAL TRIAL REGISTRATION INFORMATION: Group-Based Behavioral Therapy Combined With Stimulant Medication for Treating Children With Attention Deficit Hyperactivity Disorder and Impaired Mood; http://clinicaltrials.gov/; NCT00632619. PMID- 26903255 TI - Prevention of Depression in At-Risk Adolescents: Predictors and Moderators of Acute Effects. AB - OBJECTIVE: To assess predictors and moderators of a cognitive-behavioral prevention (CBP) program for adolescent offspring of parents with depression. METHOD: This 4-site randomized trial evaluated CBP compared to usual community care (UC) in 310 adolescents with familial (parental depression) and individual (youth history of depression or current subsyndromal symptoms) risk for depression. As previously reported by Garber and colleagues, a significant prevention effect favored CBP through 9 months; however, outcomes of CBP and UC did not significantly differ when parents were depressed at baseline. The current study expanded on these analyses and examined a range of demographic, clinical, and contextual characteristics of families as predictors and moderators and used recursive partitioning to construct a classification tree to organize clinical response subgroups. RESULTS: Depression onset was predicted by lower functioning (hazard ratio [HR] = 0.95, 95% CI = 0.92-0.98) and higher hopelessness (HR = 1.06, 95% CI = 1.01-1.11) in adolescents. The superior effect of CBP was diminished when parents were currently depressed at baseline (HR = 6.38, 95% CI = 2.38-17.1) or had a history of hypomania (HR = 67.5, 95% CI = 10.9-417.1), or when adolescents reported higher depressive symptoms (HR = 1.04, 95% CI = 1.00 1.08), higher anxiety (HR = 1.05, 95% CI = 1.01-1.08), higher hopelessness (HR = 1.10, 95% CI = 1.01-1.20), or lower functioning (HR = 0.94, 95% CI = 0.89-1.00) at baseline. Onset rates varied significantly by clinical response cluster (0% 57%). CONCLUSION: Depression in adolescents can be prevented, but programs may produce superior effects when timed at moments of relative wellness in high-risk families. Future programs may be enhanced by targeting modifiable negative clinical indicators of response. CLINICAL TRIAL REGISTRATION INFORMATION: Prevention of Depression in At-Risk Adolescents; http://clinicaltrials.gov/; NCT00073671. PMID- 26903257 TI - Marital Hostility, Hostile Parenting, and Child Aggression: Associations from Toddlerhood to School Age. AB - OBJECTIVE: The spillover hypothesis suggests that childhood aggression results from spillover of interparental conflict to poor parenting, which promotes aggressive child behavior. This study was designed to examine the spillover hypothesis in non-genetically related parent-child dyads from the toddler period through age 6 years. METHOD: A sample of 361 sets of children, adoptive parents, and birth parents from the Early Growth and Development Study (EGDS) was assessed from child age 9 months to 6 years on measures of adoptive parent financial strain, antisocial traits, marital hostility, hostile parenting, and child aggression. Structural equation modeling was used to examine links from financial strain, parent antisocial traits, and marital hostility in infancy and toddlerhood to hostile parenting and child aggression at ages 4.5 and 6 years. RESULTS: Spillover of marital conflict from child age 18 to 27 months was associated with more parental hostility in mothers and fathers at 27 months. In turn, adoptive fathers' parental hostility, but not mothers', was associated with aggression in children at age 4.5 years. However, there was no significant spillover from hostile parenting at 4.5 years to child aggression at 6 years. Birth mother antisocial traits were unassociated with child aggression. CONCLUSION: This study is the first to examine spillover of marital hostility to parenting to child aggression from toddlerhood through age 6 years in an adoption design, highlighting the impact of these environmental factors from the toddler to preschool period. The findings support the potential benefit of early identification of marital hostility. PMID- 26903258 TI - Dr. Whalen et al. reply. PMID- 26903259 TI - Validity of Measurement of Suicidal Ideas in Very Young Children. PMID- 26903261 TI - Synthesis and characterization of potassium aryl- and alkyl-substituted silylchalcogenolate ligands. AB - Treatment of either triphenyl(chloro)silane or tert-butyldiphenyl(chloro)silane with potassium metal in THF, followed by addition of 18-crown-6, affords [K(18 crown-6)][SiPh3] () and [K(18-crown-6)][SiPh2(t)Bu] (), respectively, as the reaction products in high yield. Compounds and were fully characterized including by multi-nuclear NMR, UV/vis and IR spectroscopies. Addition of elemental chalcogen to either or , results in facile chalcogen insertion into the potassium silicon bond to afford the silylchalcogenolates, [K(18-crown-6)][E-SiPh2R] (E = S, R = Ph (); E = Se, R = Ph (); E = Te, R = Ph (); E = S, R = (t)Bu (); E = Se, R = (t)Bu (); E = Te, R = (t)Bu ()), in moderate to good yield. The silylchalcogenolates reported herein were characterized by multi-nuclear NMR, UV/vis and IR spectroscopies, and their solid-state molecular structures were determined by single-crystal X-ray crystallography. Importantly, the reported compounds crystallize as discrete monomers in the solid-state, a structural feature not previously observed in silylchalcogenolates, providing well-defined access routes into systematic metal complexation studies. PMID- 26903262 TI - Occupational health scenario of Indian informal sector. AB - Workers in the Indian informal sector are engaged with different occupations. These occupations involve varied work related hazards. These occupational hazards are a consequent risk to health. The study aimed to determine occupational health scenario in the Indian Informal sector. One thousand eleven hundred twenty two workers from five different occupations namely weaving (handloom and power loom), construction, transportation, tobacco processing and fish processing were assessed by interviewer administered health questionnaire. Workers suffered from musculo-skeletal complaints, respiratory health hazards, eye problems and skin related complaints. There was a high prevalence of self-reported occupational health problems in the selected sectors. The study finds that workers have occupational exposures to multiple hazards. The absence of protective guards aggrevate their health condition. The study attempts to draws an immediate attention on the existing health scenario of the Indian Informal sector. PMID- 26903263 TI - Genome-wide analysis of aberrantly expressed microRNAs in bronchoalveolar lavage fluid from patients with silicosis. AB - Background To identify differentially expressed miRNAs profiles in bronchoalveolar lavage fluid (BALF) from patients with silicosis and consider the potential contribution of miRNAs to silicosis.Methods miRNAs expression profiling were performed in the cell fraction of BALF samples obtained from 9 subjects (3 silicosis observation subjects, 3 stage I and stage II silicosis patients, respectively). The differential expression of two selected miRNAs hsa-miR-181c-5p and hsa-miR-29a-3p were confirmed by RT-qPCR. Furthermore, miRNAs Gene Ontology Enrichment categories and target mRNAs were determined based on miRWalk.Results We found 110 dysregulated miRNAs in silicosis samples, most of which showed a down-regulation trend. Microarray results were confirmed by RT-qPCR. With the observation group samples set as standards, stage I samples showed 123 differentially expressed miRNAs, and stage II 46. 23 miRNAs were dysregulated in both stages. Finally, functional enrichment analysis indicated that these miRNAs played an important role in various biological processes, including ECM-receptor interaction and endocytosis.Conclusions This is the first time to acquire the BALF-derived microRNAs expression profiling targeting to human silicosis. These results contribute to unravelling miRNAs involved in the pathogenesis of silicosis, and provide new tools of potential use of as biomarkers for diagnosis and/or therapeutic purposes. PMID- 26903265 TI - Racotumomab for treating lung cancer and pediatric refractory malignancies. AB - INTRODUCTION: Racotumomab (originally known as 1E10 mAb) is an anti-idiotype murine IgG1 directed to membrane glycoconjugates expressed in aggressive solid tumors. It was developed as a mirror image of the idiotype of another antibody against N-glycolyl-containing molecules, such as the NeuGcGM3 ganglioside. After a successful phase II/III study, racotumomab formulated in alum was conditionally approved in Latin American countries as maintenance therapy for advanced non small cell lung cancer. AREAS COVERED: This review analyzes the biology of the target antigen, summarizes preclinical studies and discusses clinical trials in adults and the pediatric experience with racotumomab. EXPERT OPINION: Proper patient selection and combination with chemotherapy, radiotherapy or checkpoint inhibitors appear to be critical issues to maximize the effects of racotumomab vaccination in lung cancer. In a recent phase I clinical trial in children with relapsed or resistant neuroectodermal malignancies, racotumomab was well tolerated and immunogenic, and its evaluation as immunotherapy for high-risk neuroblastoma is warranted. PMID- 26903264 TI - 2-Photon Characterization of Optical Proteolytic Beacons for Imaging Changes in Matrix-Metalloprotease Activity in a Mouse Model of Aneurysm. AB - Abdominal aortic aneurysm is a multifactorial disease that is a leading cause of death in developed countries. Matrix-metalloproteases (MMPs) are part of the disease process, however, assessing their role in disease initiation and progression has been difficult and animal models have become essential. Combining Forster resonance energy transfer (FRET) proteolytic beacons activated in the presence of MMPs with 2-photon microscopy allows for a novel method of evaluating MMP activity within the extracellular matrix (ECM). Single and 2-photon spectra for proteolytic beacons were determined in vitro. Ex vivo experiments using the apolipoprotein E knockout angiotensin II-infused mouse model of aneurysm imaged ECM architecture simultaneously with the MMP-activated FRET beacons. 2-photon spectra of the two-color proteolytic beacons showed peaks for the individual fluorophores that enable imaging of MMP activity through proteolytic cleavage. Ex vivo imaging of the beacons within the ECM revealed both microstructure and MMP activity. 2-photon imaging of the beacons in aneurysmal tissue showed an increase in proteolytic cleavage within the ECM (p<0.001), thus indicating an increase in MMP activity. Our data suggest that FRET-based proteolytic beacons show promise in assessing MMP activity within the ECM and will therefore allow future studies to identify the heterogeneous distribution of simultaneous ECM remodeling and protease activity in aneurysmal disease. PMID- 26903266 TI - Evaluation of neopterin as a biomarker for the monitoring of Gaucher disease patients. AB - OBJECTIVES: Biomarker research is an important area of investigation in Gaucher disease, caused by an inherited deficiency of a lysosomal enzyme, glucocerebrosidase. We evaluated the usefulness of neopterin, as a novel biomarker reflecting chronic inflammation and immune system activation in Gaucher disease and analysed its evolution in response to enzyme replacement therapy (ERT). METHODS: Circulating plasma neopterin levels in 31 patients with non neuronopathic Gaucher disease were measured before and after the onset of ERT and were compared with those of 18 healthy controls. Plasma chitotriosidase activity was also monitored, as a reference biomarker, against which we evaluated the evolution of neopterin. RESULTS: Neopterin levels were significantly increased in treatment-naive patients (mean 11.90 +/- 5.82 nM) compared with controls (6.63 +/ 5.59 nM, Mann-Whitney U test P = 0.001), but returned to normal levels (6.92 +/- 4.66 nM) following ERT. Investigating the diagnostic value of neopterin by receiver operating characteristic analysis, we found a cut-off value of 7.613 nM that corresponds to an area under the curve of 0.780 and indicates a good discrimination capacity, with a sensitivity of 0.774 and a specificity of 0.778. DISCUSSION: Our results suggest that measurement of circulating neopterin may be considered as a novel test for the confirmation of diagnosis and monitoring of the efficacy of therapeutic intervention in Gaucher disease. Plasma neopterin levels reflect the global accumulation and activation of Gaucher cells and the extent of chronic immune activation in this disorder. CONCLUSION: Neopterin may be an alternative storage cell biomarker in Gaucher disease, especially in chitotriosidase-deficient patients. PMID- 26903269 TI - Depression and risk of type 2 diabetes: the potential role of metabolic factors. AB - The aim of the present study was to evaluate the interaction between depressive symptoms and metabolic dysregulations as risk factors for type 2 diabetes. The sample comprised of 2525 adults who participated in a baseline and a follow-up assessment over a 4.5-year period in the Emotional Health and Wellbeing Study (EMHS) in Quebec, Canada. A two-way stratified sampling design was used, on the basis of the presence of depressive symptoms and metabolic dysregulation (obesity, elevated blood sugar, high blood pressure, high levels of triglycerides and decreased high-density lipoprotein). A total of 87 (3.5%) individuals developed diabetes. Participants with both depressive symptoms and metabolic dysregulation had the highest risk of diabetes (adjusted odds ratio=6.61, 95% confidence interval (CI): 4.86-9.01), compared with those without depressive symptoms and metabolic dysregulation (reference group). The risk of diabetes in individuals with depressive symptoms and without metabolic dysregulation did not differ from the reference group (adjusted odds ratio=1.28, 95% CI: 0.81-2.03), whereas the adjusted odds ratio for those with metabolic dysregulation and without depressive symptoms was 4.40 (95% CI: 3.42-5.67). The Synergy Index (SI=1.52; 95% CI: 1.07-2.17) suggested that the combined effect of depressive symptoms and metabolic dysregulation was greater than the sum of individual effects. An interaction between depression and metabolic dysregulation was also suggested by a structural equation model. Our study highlights the interaction between depressive symptoms and metabolic dysregulation as a risk factor for type 2 diabetes. Early identification, monitoring and a comprehensive management approach of both conditions might be an important diabetes prevention strategy. PMID- 26903268 TI - TSPAN5, ERICH3 and selective serotonin reuptake inhibitors in major depressive disorder: pharmacometabolomics-informed pharmacogenomics. AB - Millions of patients suffer from major depressive disorder (MDD), but many do not respond to selective serotonin reuptake inhibitor (SSRI) therapy. We used a pharmacometabolomics-informed pharmacogenomics research strategy to identify genes associated with metabolites that were related to SSRI response. Specifically, 306 MDD patients were treated with citalopram or escitalopram and blood was drawn at baseline, 4 and 8 weeks for blood drug levels, genome-wide single nucleotide polymorphism (SNP) genotyping and metabolomic analyses. SSRI treatment decreased plasma serotonin concentrations (P<0.0001). Baseline and plasma serotonin concentration changes were associated with clinical outcomes (P<0.05). Therefore, baseline and serotonin concentration changes were used as phenotypes for genome-wide association studies (GWAS). GWAS for baseline plasma serotonin concentrations revealed a genome-wide significant (P=7.84E-09) SNP cluster on chromosome four 5' of TSPAN5 and a cluster across ERICH3 on chromosome one (P=9.28E-08) that were also observed during GWAS for change in serotonin at 4 (P=5.6E-08 and P=7.54E-07, respectively) and 8 weeks (P=1.25E-06 and P=3.99E-07, respectively). The SNPs on chromosome four were expression quantitative trait loci for TSPAN5. Knockdown (KD) and overexpression (OE) of TSPAN5 in a neuroblastoma cell line significantly altered the expression of serotonin pathway genes (TPH1, TPH2, DDC and MAOA). Chromosome one SNPs included two ERICH3 nonsynonymous SNPs that resulted in accelerated proteasome-mediated degradation. In addition, ERICH3 and TSPAN5 KD and OE altered media serotonin concentrations. Application of a pharmacometabolomics-informed pharmacogenomic research strategy, followed by functional validation, indicated that TSPAN5 and ERICH3 are associated with plasma serotonin concentrations and may have a role in SSRI treatment outcomes. PMID- 26903267 TI - A meta-analysis of blood cytokine network alterations in psychiatric patients: comparisons between schizophrenia, bipolar disorder and depression. AB - Schizophrenia, bipolar disorder and major depressive disorder (MDD) have all been associated with aberrant blood cytokine levels; however, neither the pattern of cytokine alterations nor the impact of clinical status have been compared across disorders. We performed a meta-analysis of blood cytokines in acutely and chronically ill patients with these major psychiatric disorders. Articles were identified by searching the PubMed, PsycInfo and Web of Science, and the reference lists of these studies. Sixty-eight studies met the inclusion criteria (40 schizophrenia, 10 bipolar disorder and 18 MDD) for acutely ill patients. Forty-six studies met the inclusion criteria (18 schizophrenia, 16 bipolar disorder and 12 MDD) for chronically ill patients. Levels of two cytokines (interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha)), one soluble cytokine receptor (sIL-2R), and one cytokine receptor antagonist (IL-1RA) were significantly increased in acutely ill patients with schizophrenia, bipolar mania and MDD compared with controls (P<0.01). Following treatment of the acute illness, IL-6 levels significantly decreased in both schizophrenia and MDD (P<0.01); sIL-2R levels increased in schizophrenia; and IL-1RA levels in bipolar mania decreased. In chronically ill patients, the levels of IL-6 were significantly increased in schizophrenia, euthymic (but not depressed) bipolar disorder and MDD compared with controls (P<0.01). The levels of IL-1beta and sIL 2R were significantly increased in both chronic schizophrenia and euthymic bipolar disorder. Overall, there were similarities in the pattern of cytokine alterations in schizophrenia, bipolar disorder and MDD during acute and chronic phases of illness, raising the possibility of common underlying pathways for immune dysfunction. Effects of treatment on cytokines were more robust for schizophrenia and MDD, but were more frequently studied than for acute mania. These findings have important implications for our understanding of the pathophysiology and treatment of major psychiatric disorders. PMID- 26903270 TI - Response to Dr Fried & Dr Kievit, and Dr Malhi et al. PMID- 26903271 TI - Progression from selective to general involvement of hippocampal subfields in schizophrenia. AB - Volume deficits of the hippocampus in schizophrenia have been consistently reported. However, the hippocampus is anatomically heterogeneous; it remains unclear whether certain portions of the hippocampus are affected more than others in schizophrenia. In this study, we aimed to determine whether volume deficits in schizophrenia are confined to specific subfields of the hippocampus and to measure the subfield volume trajectories over the course of the illness. Magnetic resonance imaging scans were obtained from Data set 1: 155 patients with schizophrenia (mean duration of illness of 7 years) and 79 healthy controls, and Data set 2: an independent cohort of 46 schizophrenia patients (mean duration of illness of 18 years) and 46 healthy controls. In addition, follow-up scans were collected for a subset of Data set 1. A novel, automated method based on an atlas constructed from ultra-high resolution, post-mortem hippocampal tissue was used to label seven hippocampal subfields. Significant cross-sectional volume deficits in the CA1, but not of the other subfields, were found in the schizophrenia patients of Data set 1. However, diffuse cross-sectional volume deficits across all subfields were found in the more chronic and ill schizophrenia patients of Data set 2. Consistent with this pattern, the longitudinal analysis of Data set 1 revealed progressive illness-related volume loss (~2-6% per year) that extended beyond CA1 to all of the other subfields. This decline in volume correlated with symptomatic worsening. Overall, these findings provide converging evidence for early atrophy of CA1 in schizophrenia, with extension to other hippocampal subfields and accompanying clinical sequelae over time. PMID- 26903273 TI - A potential therapeutic peptide-based neutralizer that potently inhibits Shiga toxin 2 in vitro and in vivo. AB - Shiga toxin 2 (Stx2) is a major virulence factor in infections with Stx-producing Escherichia coli (STEC), which can cause serious clinical complications in humans, such as hemolytic uremic syndrome (HUS). Recently, we screened and identified two peptide-based Stx2 neutralizers, TF-1 and WA-8, which specifically and directly bind to Stx2. Computer simulations suggested that the majority of TF 1 or WA-8 binds tightly at the receptor-binding site 3 of Stx2. The two peptides also effectively inhibited the cytotoxic activity of Stx2 by blocking the binding of Stx2 to target cells. TF-1 exhibits remarkable therapeutic potency in both mice and rat toxicity models. In mice toxicity models, TF-1 provided full protection when mice were injected with 5 LD50 of Stx2. In rat toxicity models, TF-1 reduced fatal tissue damage and completely protected rats from the lethal challenges of Stx2. In these rats, TF-1 significantly decreased the concentration of Stx2 in blood and diminished tissue distribution levels of Stx2. Furthermore, TF-1 effectively protected rats from the pathological effects caused by Stx2, especially in the kidney, thymus, adrenal gland, and lung. Taken together, these results indicate that TF-1 is a promising therapeutic agent against the pathogenicity of Stx2. PMID- 26903274 TI - Isotopic disequilibrium in Globigerina bulloides and carbon isotope response to productivity increase in Southern Ocean. AB - Oxygen and carbon isotope ratios in planktonic foraminifera Globigerina bulloides collected from tow samples along a transect from the equatorial Indian ocean to the Southern Ocean (45 degrees E and 80 degrees E and 10 degrees N to 53 degrees S) were analysed and compared with the equilibrium delta(18)O and delta(13)C values of calcite calculated using the temperature and isotopic composition of the water column. The results agree within ~0.250/00 for the region between 10 degrees N and 40 degrees S and 75-200 m water depth which is considered to be the habitat of Globigerina bulloides. Further south (from 40 degrees S to 55 degrees S), however, the measured delta(18)O and delta(13)C values are higher than the expected values by ~20/00 and ~10/00 respectively. These enrichments can be attributed to either a 'vital effect' or a higher calcification rate. An interesting pattern of increase in the delta(13)C(DIC) value of the surface water with latitude is observed between 35 degrees S and~ 60 degrees S, with a peak at~ 42 degrees S. This can be caused by increased organic matter production and associated removal. A simple model accounting for the increase in the delta(13)C(DIC) values is proposed which fits well with the observed chlorophyll abundance as a function of latitude. PMID- 26903272 TI - Predicting clinical outcome from reward circuitry function and white matter structure in behaviorally and emotionally dysregulated youth. AB - Behavioral and emotional dysregulation in childhood may be understood as prodromal to adult psychopathology. Additionally, there is a critical need to identify biomarkers reflecting underlying neuropathological processes that predict clinical/behavioral outcomes in youth. We aimed to identify such biomarkers in youth with behavioral and emotional dysregulation in the Longitudinal Assessment of Manic Symptoms (LAMS) study. We examined neuroimaging measures of function and white matter in the whole brain using 80 youth aged 14.0 (s.d.=2.0) from three clinical sites. Linear regression using the LASSO (Least Absolute Shrinkage and Selection Operator) method for variable selection was used to predict severity of future behavioral and emotional dysregulation measured by the Parent General Behavior Inventory-10 Item Mania Scale (PGBI-10M)) at a mean of 14.2 months follow-up after neuroimaging assessment. Neuroimaging measures, together with near-scan PGBI-10M, a score of manic behaviors, depressive behaviors and sex, explained 28% of the variance in follow-up PGBI-10M. Neuroimaging measures alone, after accounting for other identified predictors, explained ~1/3 of the explained variance, in follow-up PGBI-10M. Specifically, greater bilateral cingulum length predicted lower PGBI-10M at follow-up. Greater functional connectivity in parietal-subcortical reward circuitry predicted greater PGBI-10M at follow-up. For the first time, data suggest that multimodal neuroimaging measures of underlying neuropathologic processes account for over a third of the explained variance in clinical outcome in a large sample of behaviorally and emotionally dysregulated youth. This may be an important first step toward identifying neurobiological measures with the potential to act as novel targets for early detection and future therapeutic interventions. PMID- 26903275 TI - Drug permeation and barrier damage in Leishmania-infected mouse skin. AB - OBJECTIVES: Pathological disorder can disrupt the barrier integrity of the skin, thereby altering the drug delivery from topical formulations to the target site. Cutaneous leishmaniasis (CL) is an infection of the dermal layers of the skin and manifests as a variety of skin lesions from defined nodular forms to plaques and chronic ulcers. The aim of this work was to characterize the physiology and barrier integrity of the Leishmania-infected BALB/c mouse skin and how they impacted delivery of drugs into the skin. METHODS: A histological evaluation of the structural differences between uninfected and infected skin was performed using haematoxylin/eosin, elastic Van Gieson and Iba-1 stains. As a CL nodule developed and progressed, the skin pH, hydration and trans-epidermal water loss (TEWL) were recorded. Finally, Franz diffusion cells were used to evaluate the influence of the infection on drug delivery through the skin. RESULTS: We found: (i) structural changes in both the epidermal and dermal layers due to the ingress of inflammatory cells, as shown by immunohistochemistry; (ii) a significant increase in TEWL; and (iii) significantly higher permeation of the model permeants caffeine and ibuprofen and the antileishmanial drugs buparvaquone and paromomycin, for Leishmania-infected skin compared with uninfected skin. The infection had no measurable influence on skin pH and hydration. CONCLUSIONS: We report profound changes in the skin barrier physiology, function and permeability to drugs of Leishmania-infected skin. PMID- 26903276 TI - Genetic environment of the transferable oxazolidinone/phenicol resistance gene optrA in Enterococcus faecalis isolates of human and animal origin. AB - OBJECTIVES: Aim of this study was to analyse 17 non-related Enterococcus faecalis isolates of human and animal origin for the genetic environment of the novel oxazolidinone/phenicol resistance gene optrA. METHODS: WGS and de novo assembly were conducted to analyse the flanking sequences of the optrA gene in the 17 E. faecalis isolates. When optrA was located on a plasmid, conjugation assays were performed to check whether the plasmids are conjugative and to confirm the resistance phenotype associated with these plasmids. RESULTS: All nine optrA carrying plasmids were conjugated into E. faecalis JH2-2 and the transconjugants exhibited the optrA-associated phenotype. In these plasmids, an IS1216E element was detected either upstream and/or downstream of the optrA gene. In eight plasmids, the phenicol exporter gene fexA was found upstream of optrA and in six plasmids, a novel erm(A)-related gene for macrolide-lincosamide-streptogramin B resistance was detected downstream of optrA. When located in the chromosomal DNA, the optrA gene was found downstream of the transcriptional regulator gene araC in four isolates, or downstream of the fexA gene in another four isolates. Integration of the optrA region into a Tn558-Tn554 hybrid, located in the chromosomal radC gene, was seen in two isolates. CONCLUSIONS: The findings of the present study extend the current knowledge about the genetic environment of optrA and suggest that IS1216E elements play an important role in the dissemination of optrA among different types of enterococcal plasmids. The mechanism underlying the integration of optrA into the chromosomal DNA requires further investigation. PMID- 26903277 TI - Evaluation of the efficacy and tolerance of a short 7 day third-generation cephalosporin treatment in the management of acute pyelonephritis in young women in the emergency department. AB - OBJECTIVES: Urinary tract infections, among the leading causes of antibiotic prescriptions in adult women, are complicated by increasing antibiotic resistance. Current recommendations propose a 7 day treatment with fluoroquinolones or a 10-14 day course of third-generation cephalosporins (3GC). Our aim was to study the efficiency and tolerance of a short 7 day treatment with 3GC in uncomplicated acute pyelonephritis in women aged between 18 and 65 years. PATIENTS AND METHODS: This study was an open, prospective, non-comparative, monocentric pilot study with consecutive patients. We included women between 18 and 65 years old who had been admitted to the emergency department with a diagnosis of acute pyelonephritis. The treatment consisted of 1 g of ceftriaxone injection followed by 6 days of 400 mg of cefixime per day. The primary endpoint was negative urine cultures on day 9. We opted for Fleming's multistage design for this trial. ClinicalTrials.gov number: NCT01390623. RESULTS: Thirty-seven patients were analysed. The bacteriological response consisted of negative urine cultures for all 37 patients on day 9. On day 9, 30 patients were completely asymptomatic, while 7 exhibited clinical improvement though persistence of bladder irritation or flank pain. On day 37, there were no remaining symptoms and no recurrences of urinary tract infection, as noted during the last follow-up visits. CONCLUSIONS: These results suggest that acute pyelonephritis in women could be successfully treated with a short-term course of 1 g of ceftriaxone on the first day followed by 400 mg of cefixime per day for 6 days. These positive results must be confirmed by a non-inferiority study. PMID- 26903279 TI - pHN7A8-related multiresistance plasmids (blaCTX-M-65, fosA3 and rmtB) detected in clinical isolates of Klebsiella pneumoniae from Bolivia: intercontinental plasmid dissemination? PMID- 26903278 TI - Statin adjunctive therapy shortens the duration of TB treatment in mice. AB - BACKGROUND: The repurposing of existing agents may accelerate TB drug development. Recently, we reported that the lipid-lowering drug simvastatin, when added to the first-line antitubercular regimen, reduces the lung bacillary burden in chronically infected mice. OBJECTIVES: We investigated whether the addition of simvastatin to the first-line regimen (isoniazid/rifampicin/pyrazinamide) shortens the duration of curative TB treatment in mice. METHODS: Mycobacterium tuberculosis-infected THP-1 cells were exposed to simvastatin to determine the effect of statins on the activity of first-line anti-TB drug activity and intracellular rifampicin concentration. Single-dose and steady-state pharmacokinetic studies guided optimized simvastatin dosing in vivo. BALB/c mice were aerosol-infected with M. tuberculosis H37Rv and drug treatment was initiated 6 weeks post-infection. Separate groups of mice received standard TB treatment with or without simvastatin. Relapse rates were assessed 3 months after discontinuation of each treatment regimen. MALDI-MS imaging was used to image the cholesterol content of mouse lung lesions. RESULTS: Simvastatin significantly enhanced the bactericidal activity of first-line drugs against intracellular M. tuberculosis without altering intracellular rifampicin concentrations. Adjunctive treatment with 60 mg/kg simvastatin shortened the time required to achieve culture-negative lungs from 4.5 to 3.5 months. Following 2.5, 3.5 and 4.5 months of treatment, relapse rates were 100%, 50% and 0%, respectively, in the control group and 50% (P = 0.03), 20% and 0%, respectively, in the statin group. Simvastatin did not alter plasma or lung lesion cholesterol levels. CONCLUSIONS: Statins are attractive candidates for host-directed, adjunctive TB therapy. Further preclinical studies are needed to define the optimal statin and dosing. PMID- 26903280 TI - Deprotonation of Water Ligands in V, Cr, Mn, Fe, and Co Complexes Reduces Oxidation-Driven Carboxylate Ligand Frequency Shifts. AB - In Mn complexes, it has been shown that oxidation-driven changes in carboxylate ligand vibrations are suppressed, if a water or hydroxo ligand is simultaneously deprotonated. Deprotonation with oxidation has also been shown to greatly reduce the dependence of Mn complex redox energies on the oxidation state of the metal. We have here investigated the effect of oxidation with deprotonation on the carboxylate ligand frequencies of V, Cr, Mn, Fe, and Co complexes. The effects of anionic ligand substitution (instead of deprotonation) and solvent dielectric were also investigated to determine the mechanism that drives carboxylate frequency shifts. It is shown that the effect of deprotonation was similar for all of the metals tested in this study. C-O bond lengths and O-C-O angle changes in the carboxylate ligand were also reduced by deprotonation. Furthermore, the effect of anionic ligand substitution was similar to deprotonation in the suppression of carboxylate frequency shifts. These shifts were also reduced by increases in the solvent dielectric, in the absence of charge conservation through deprotonation. Therefore, we conclude that carboxylate frequency shifts are largely driven by electrostatic effects. PMID- 26903281 TI - T cell-specific inactivation of mouse CD2 by CRISPR/Cas9. AB - The CRISPR/Cas9 system can be used to mutate target sequences by introduction of double-strand breaks followed by imprecise repair. To test its use for conditional gene editing we generated mice transgenic for CD4 promoter-driven Cas9 combined with guide RNA targeting CD2. We found that within CD4(+) and CD8(+) lymphocytes from lymph nodes and spleen 1% and 0.6% were not expressing CD2, respectively. T cells lacking CD2 carryied mutations, which confirmed that Cas9 driven by cell-type specific promoters can edit genes in the mouse and may thus allow targeted studies of gene function in vivo. PMID- 26903283 TI - Liver Function Testing Is Not Useful in the Diagnosis of Sarcoidosis in Patients Presenting with Uveitis. AB - PURPOSE: To elucidate the usefulness of abnormal liver function tests in the diagnosis of sarcoidosis in patients presenting with ocular inflammation. METHODS: Retrospective comparison of sample populations of 100 patients each with sarcoidosis-associated uveitis (SAU) and non-sarcoid uveitis controls. RESULTS: Number of abnormal results between SAU and control groups were: (1) raised alkaline phosphatase 6:2; (2) raised alanine aminotransferase 21:19; (3) raised total protein 14:5; (4) hypoalbuminemia 0:7; (5) raised bilirubin 1:2. The only parameters reaching statistical significance were in (3), using any elevated result; and (4), the greater risk being in controls. CONCLUSIONS: There is no evidence that abnormal liver function tests are an indicator of sarcoidosis in new patients presenting with uveitis. PMID- 26903282 TI - Clinical characteristics associated with mortality of patients with anaerobic bacteremia. AB - The presence of anaerobes in the blood stream is known to be associated with a higher rate of mortality. However, few prognostic risk factor analyses examining whether a patient's background characteristics are associated with the prognosis have been reported. We performed a retrospective case-controlled study to assess the prognostic factors associated with death from anaerobic bacteremia. Seventy four patients with anaerobic bacteremia were treated between January 2005 and December 2014 at Aichi Medical University Hospital. The clinical information included drug susceptibility was used for analysis of prognostic factors for 30 day mortality. Multivariate logistic analyses revealed an association between the 30-day mortality rate and malignancy (OR: 3.64, 95% CI: 1.08-12.31) and clindamycin resistance (OR: 7.93, 95% CI: 2.33-27.94). The result of Kaplan-Meier analysis of mortality showed that the 30-day survival rate was 83% in clindamycin susceptible and 38.1% in clindamycin resistant anaerobes causing bacteremia. The result of log-rank test also showed that susceptibility to clindamycin affected mortality (P < 0.001). Our results indicated that malignancy and clindamycin susceptibility could be used to identify subgroups of patients with anaerobic bacteremia with a higher risk of 30-day mortality. The results of this study are important for the early and appropriate management of patients with anaerobic bacteremia. PMID- 26903284 TI - Direct observation of negative-index microwave surface waves. AB - Waves propagating in a negative-index material have wave-front propagation (wavevector, k) opposite in direction to that of energy flow (Poynting vector, S). Here we present an experimental realisation at microwave frequencies of an analogous surface wave phenomenon whereby a metasurface supports a surface mode that has two possible wavevector eigenstates within a narrow band of frequencies: one that supports surface waves with positive mode index, and another that supports surface waves with negative mode index. Phase sensitive measurements of the near-field of surface waves across the metasurface show the contrasting spatial evolution of the two eigenstates, providing a unique opportunity to directly observe the negative-index phenomenon. PMID- 26903286 TI - Cardiopulmonary resuscitation quality: Widespread variation in data intervals used for analysis. AB - AIM: There is a growing body of evidence for the relationship between CPR quality and survival in cardiac arrest patients. We sought to describe the characteristics of the analysis intervals used across studies. METHODS: Relevant papers were selected as described in our recent systematic review. From these papers we collected information about (1) the time interval used for analysis; (2) the event that marked the beginning of the analysis interval; and (3) the minimum amount of CPR quality data required for a case to be included in the analysed cohort. We then compared this data across papers. RESULTS: Twenty-one studies reported on the association between CPR quality and cardiac arrest patient survival. In two thirds of studies data from the start of the resuscitation episode was analysed, in particular the first 5min. Commencement of the analysis interval was marked by various events including ECG pad placement and first chest compression. Nine studies specified a minimum amount of data that had to have been collected for the individual case to be included in the analysis; most commonly 1min of data. The use of shorter intervals allowed for inclusion of more cases as it included cases that did not have a complete dataset. CONCLUSION: To facilitate comparisons across studies, a standardised definition of the data analysis interval should be developed; one that maximises the amount of cases available without compromising the data's representability of the resuscitation effort. PMID- 26903287 TI - Does early withdrawal of life-sustaining treatment increase mortality after cardiac arrest? PMID- 26903285 TI - Adenylate kinase: a novel antigen for immunodiagnosis and subunit vaccine against tuberculosis. AB - Mycobacterium tuberculosis (M.tb)-derived antigens capable of inducing strong cellular and/or humoral responses are potential targets for both immunodiagnosis and vaccine development against tuberculosis (TB). In the present study, we identified adenylate kinase (ADK, Rv0733) as an antigen that induces high cellular and antibody responses in active TB patients. We consequently tested the use of ADK-specific T cells and antibodies as biomarkers for TB diagnosis. The ADK-specific IFN-gamma-producing cells detected by ELISPOT assay showed a sensitivity of 85.0 % and specificity of 94.15 % for TB diagnosis while ADK specific IgG antibody showed a sensitivity of 40.35 % and specificity of 96.43 %. Combining ADK-specific cellular and antibody responses increased the sensitivity to 91.59 % and the specificity to 96.15 %. Immunogenicity and protection against M.tb infection were further tested in a murine model. Immunization with ADK protein elicited strong specific T- and B-cell responses, and provided protection against the virulent H37Rv stain of M.tb resulting in lower bacilli load in the spleens and lungs. More ADK-specific polyfunctional Th1 cells were observed in the lungs when compared to adjuvant-immunized mice. ADK thus may serve as a novel M.tb antigen for TB immunodiagnosis and development of subunit vaccines. KEY MESSAGES: ADK induces strong immune responses both in humans and mice. ADK specific IFN-gamma production and B-cell responses have high potential for TB diagnosis. ADK immunization provides protection against M.tb infection. PMID- 26903288 TI - Cerebral oxygenation in mechanically ventilated early cardiac arrest survivors: The impact of hypercapnia. AB - BACKGROUND: Optimal cerebral oxygenation is considered fundamental to cerebral protection in cardiac arrest (CA) patients. Hypercapnia increases cerebral blood flow and may also improve cerebral oxygenation. It is uncertain, however, whether this effect occurs in mechanically ventilated early survivors of CA. METHODS: We enrolled mechanically ventilated resuscitated patients within 36h of their cardiac arrest. We performed a prospective double cross-over physiological study comparing the impact of normocapnia (PaCO2 35-45mmHg) vs. mild hypercapnia (PaCO2 45-55mmHg) on regional cerebral tissue oxygen saturation (SctO2) assessed by near infrared spectroscopy (NIRS). RESULTS: We studied seven adult CA patients with a median time to return of spontaneous circulation of 28min at a median of 26h and 30min after CA. During normocapnia (median EtCO2 of 32mmHg [30-41mmHg] and PaCO2 of 37mmHg [32-45mmHg]) the median NIRS-derived left frontal SctO2 was 61% [52 65%] and the right frontal SctO2 was 61% [54-68%]. However, during mild hypercapnia (median EtCO2 of 49mmHg [40-57mmHg] and PaCO2 of 52mmHg [43-55mmHg) the median left frontal SctO2 increased to 69% [59-78%] and the right frontal SctO2 increased to 73% [61-76%])(p=0.001, for all comparisons). CONCLUSION: During the early post-resuscitation period, in mechanically ventilated CA patients, mild hypercapnia increases cerebral oxygenation as assessed by NIRS. Further investigations of the effect of prolonged mild hypercapnia on cerebral oxygenation and patient outcomes appear justified. PMID- 26903289 TI - A novel auto-tuning method for fractional order PI/PD controllers. AB - Fractional order PID controllers benefit from an increasing amount of interest from the research community due to their proven advantages. The classical tuning approach for these controllers is based on specifying a certain gain crossover frequency, a phase margin and a robustness to gain variations. To tune the fractional order controllers, the modulus, phase and phase slope of the process at the imposed gain crossover frequency are required. Usually these values are obtained from a mathematical model of the process, e.g. a transfer function. In the absence of such model, an auto-tuning method that is able to estimate these values is a valuable alternative. Auto-tuning methods are among the least discussed design methods for fractional order PID controllers. This paper proposes a novel approach for the auto-tuning of fractional order controllers. The method is based on a simple experiment that is able to determine the modulus, phase and phase slope of the process required in the computation of the controller parameters. The proposed design technique is simple and efficient in ensuring the robustness of the closed loop system. Several simulation examples are presented, including the control of processes exhibiting integer and fractional order dynamics. PMID- 26903290 TI - ChR2 transgenic animals in peripheral sensory system: Sensing light as various sensations. AB - Since the introduction of Channelrhodopsin-2 (ChR2) to neuroscience, optogenetics technology was developed, making it possible to activate specific neurons or circuits with spatial and temporal precision. Various ChR2 transgenic animal models have been generated and are playing important roles in revealing the mechanisms of neural activities, mapping neural circuits, controlling the behaviors of animals as well as exploring new strategy for treating the neurological diseases in both central and peripheral nervous system. An animal including humans senses environments through Aristotle's five senses (sight, hearing, smell, taste and touch). Usually, each sense is associated with a kind of sensory organ (eyes, ears, nose, tongue and skin). Is it possible that one could hear light, smell light, taste light and touch light? When ChR2 is targeted to different peripheral sensory neurons by viral vectors or generating ChR2 transgenic animals, the animals can sense the light as various sensations such as hearing, touch, pain, smell and taste. In this review, we focus on ChR2 transgenic animals in the peripheral nervous system. Firstly the working principle of ChR2 as an optogenetic actuator is simply described. Then the current transgenic animal lines where ChR2 was expressed in peripheral sensory neurons are presented and the findings obtained by these animal models are reviewed. PMID- 26903291 TI - Adjuvant-induced mono-arthritis potentiates cerebral hemorrhage in the spontaneously hypertensive rats. AB - AIMS: Patients with rheumatoid arthritis (RA), have a higher incidence of hypertension and stroke than the normal population. Currently there exists no animal model to study the pathogenic interactions of hemorrhagic stroke (HS) subsequent to chronic inflammation and hypertension. We have created and defined a hypertensive-mono-arthritic animal model who demonstrate gros signs of cerebral hemorrhage in presence of mono-arthritis. MAIN METHODS: Spontaneously hypertensive rats (SHR) were fed either a high salt diet (4% NaCl; HSD) or Purina chow (RD) from weaning. Complete Freund's adjuvant (CFA) was injected into the left hind paw at 21-28weeks (control groups received saline (SAL)). Degree of inflammation, joint swelling, weight and blood pressure were monitored for 21days. Animals were then sacrificed and their brain and left hind paw evaluated. KEY FINDINGS: All groups were hypertensive throughout the experimental period (>180mmHg systolic), irrespective of diet. Both CFA groups produced significant local inflammatory response in their injected paw with associated joint degradation and cellular infiltrates. Systemic plasma TNF-alpha levels were significantly elevated in CFA groups, with significant increase in TNF-alpha at 7 and 14days, compared to SAL groups. Cerebral hemorrhage was visualized in the CFA groups but not SAL controls, with a higher severity in HSD-CFA group. SIGNIFICANCE: The mono-arthritic hypertensive animals are capable of developing HS upon induction of inflammatory insult. The HSD appears to exacerbate the inflammatory response and influence degree of the hemorrhage. Our novel, multi disease model may provide an appropriate platform to study the pathogenesis of HS among arthritic patients. PMID- 26903292 TI - Effect of alpha 2,6 sialylation on integrin-mediated adhesion of breast cancer cells to fibronectin and collagen IV. AB - AIMS: To determine the role of sialylation on alpha5beta1 and alpha2beta1 integrins in the regulation of adhesion between breast cancer cells and extracellular matrix (ECM). MAIN METHODS: Static cell adhesion assays were performed to quantify avidity of breast cancer cells to ECM. The effects of sialidases on alpha2,6 sialylation was assessed by flow cytometry using biotin conjugated Sambucus nigra lectin. Lectin affinity assays were used to determine expression of alpha2,6 sialylated integrins. Cell migration and invasion were investigated by wound healing and transwell invasion assays. KEY FINDINGS: alpha2, alpha5 and beta1 integrins had considerable alpha2,6 sialylation on MDA MB-231 cells, whereas signals from MCF-7 cells were undetectable. Cleavage of alpha2,6 sialylation increased adhesion of MDA-MB-231 cells to ECM, while adhesion of MCF-7 cells was unaffected, consistent with the latter's lack of endogenous alpha2,6 sialylated surface integrins. Neither surface expression of alpha2beta1 and alpha5beta1 integrins, nor activated beta1 integrin, changed in MDA-MB-231 cells after sialidase treatment. However, sialidase treatment did not have significant impact on migration or invasion of MDA-MB-231 cells. SIGNIFICANCE: Cell adhesion is an important early step of cancer metastasis, yet the roles of sialylation in regulating integrin-mediated breast cancer cell adhesion in comparison to migration and invasion are not well-understood. Our data suggest desialylation of alpha2,6-sialylated integrins increases adhesion, but not migration or invasion, of MDA-MB-231 cells to ECM without altering integrin expression. It should be considered that alpha2,6 sialylation may play different roles in regulating cell adhesion of different cancer cells when developing potential therapeutics targeting alpha2,6 sialylation. PMID- 26903293 TI - Assessment of dietary lutein, zeaxanthin and lycopene intakes and sources in the Spanish survey of dietary intake (2009-2010). AB - We assessed the intake and major dietary sources of lutein, zeaxanthin and lycopene (non-provitamin A carotenoids) in Spain using food consumption data from the Spanish National Dietary Intake Survey (2009-2010). Three-day diaries and one 24-h recall were used to collect dietary data and a software application that includes HPLC data was used. Average intake of those carotenoids was 4290.8 MUg/d (67.1% total carotenoid intake), mainly from vegetables (3414.0 MUg/d), followed by fruits (393.5 MUg/d), oils/fats (204.0 MUg/d) and eggs/egg products (170.0 MUg/d). Main sources of lutein and zeaxanthin were vegetables (62.9% total diet, 1235.2 MUg/person/d). Lycopene intake was 3055.6 MUg/d (71.2% of non-provitamin A carotenoids), mainly from tomato and by-products (86.3%) and watermelon. Red- and orange-colored fruits and vegetables were the major contributors of non provitamin carotenoids (3219.0 MUg/person/d). Balanced diets should favor fruits and vegetables over other dietary sources (oils, eggs, processed foods) that contain components to be consumed with moderation. PMID- 26903294 TI - Domino-Style Cerebral Bleeding in a Patient With Immune Thrombocytopenic Purpura. PMID- 26903295 TI - c-Jun N-terminal kinase regulates the nucleoplasmic translocation and stability of nucleolar GLTSCR2 protein. AB - Glioblastoma tumor suppressive candidate region gene 2 (GLTSCR2) is a nucleolar protein that participates in critical cellular processes including the DNA damage response, cell cycle regulation, and inhibition of MYC-induced transforming activity. Irrespective of these important physiological and pathological functions, the mechanisms that regulate GLTSCR2 expression, and its nucleolar nucleoplasmic translocation, are largely unknown. HeLa cells were treated with various protein kinase inhibitors and subjected to immunocytochemical or immunoblot assays for GLTSCR2. Protein stability was determined by the cycloheximide chase or ubiquitination assays. Oligomer status was analyzed by immunoprecipitation. Inhibiting c-jun N-terminal kinase (JNK) phosphorylation activity on c-jun by SP600125, or adding a c-jun peptide, induced the nucleoplasmic translocation of GLTSCR2 from the nucleolus and enhanced protein degradation through the proteasome-polyubiquitination pathway. These effects may have resulted from reducing the binding affinity between GLTSCR2 monomers. These data indicate that JNK, and its phosphorylation target c-jun, are prerequisites for the nucleolar distribution of GLTSCR2 and maintenance of its protein stability. Overall, GLTSCR2 is crucial for normal cellular function as well as for preventing the development or progression of cancer. The JNK-c-jun axis is indispensible for regulating the activities of GLTSCR2. PMID- 26903297 TI - Xanthine oxidoreductase activation is implicated in the onset of metabolic arthritis. AB - A metabolic syndrome (MetS) is accompanied by hyperuricemia, during which xanthine oxidoreductase (XOR) catalyzes the production of uric acid. In the cohort study, a correlation between uric acid concentration in the synovial fluid and osteoarthritis (OA) incidence is observed. The purpose of our study was to elucidate XOR function in terms of correlation between MetS and OA. Seven week old male C57BL6J mice were fed normal diet (ND) or high fat diet (HFD) with or without febuxostat (FEB), a XOR inhibitor. HFD stimulated xanthine oxidase activity in the IPFP and the visceral fat. OA changes at the site of the knee joints had progressed due to HFD, but these changes were reduced upon FEB administration. IL-1beta expression in the HFD group was increased in accordance with the enhancement of NLRP3 or iNOS expression in the IPFP, whereas it was inhibited by FEB administration. In the organ culture system, when the IPFP was stimulated with insulin, IL-1beta expression was increased in accordance with the increase of NLRP3 expression; however, they were reduced by FEB administration. Based on the above results, we showed that inflammasome activation accompanied by an increase in XOR activity contributed to IPFP inflammation followed by OA progression. PMID- 26903296 TI - Mst1 regulates hepatic lipid metabolism by inhibiting Sirt1 ubiquitination in mice. AB - Previous study showed mammalian Ste20-like kinase (Mst1) may serve as target for the development of new therapies for diabetes. However, the function of Mst1 involved in liver lipid metabolism has remained elusive. In this study, we report that the liver of Mst1 knockout (Mst1(-/-)) mice showed more severe liver metabolic damage under fasting and high-fat diet than that of control mice. And fasting induced hepatic Mst1 expression. Mst1 overexpression inhibited Srebp-1c expression and increased the expression of antioxidant genes in primary hepatocytes. We also found that fasting-induced expression of hepatic Sirt1 was attenuated in Mst1(-/-) mice. Mst1 overexpression promoted Sirt1 expression, probably due to inhibiting Sirt1 ubiquitination. In summary, our study suggests that Mst1 regulates hepatic lipid metabolism by inhibiting Sirt1 ubiquitination in mice. PMID- 26903298 TI - Central nervous system promotes thermotolerance via FoxO/DAF-16 activation through octopamine and acetylcholine signaling in Caenorhabditis elegans. AB - The autonomic nervous system (ANS) responds to many kinds of stressors to maintain homeostasis. Although the ANS is believed to regulate stress tolerance, the exact mechanism underlying this is not well understood. To understand this, we focused on longevity genes, which have functions such as lifespan extension and promotion of stress tolerance. To understand the relationship between ANS and longevity genes, we analyzed stress tolerance of Caenorhabditis elegans treated with octopamine, which has an affinity to noradrenaline in insects, and acetylcholine. Octopamine and acetylcholine did not show resistance against H2O2, but the neurotransmitters promoted thermotolerance via DAF-16. However, chronic treatment with octopamine and acetylcholine did not extend the lifespan, although DAF-16 plays an important role in longevity. In conclusion, our results show that octopamine and acetylcholine activate DAF-16 in response to stress, but chronic induction of octopamine and acetylcholine is not beneficial for increasing longevity. PMID- 26903299 TI - Interaction of atypical cadherin Fat1 with SoHo adaptor proteins CAP/ponsin and ArgBP2. AB - Mammalian Fat1 is a giant atypical cadherin/tumor suppressor involved in the regulation of cellular orientation, migration, and growth. Fat1 is implicated in the development of the brain, eye, and kidney. Altered expression or mutations of FAT1 are also associated with cancer and facioscapulohumeral muscular dystrophy (FSHD). Yet, the mechanistic functions of this pathway remain incompletely understood. Here, we report the identification of Sorbin-homology (SoHo) proteins as novel interaction partners of Fat1 by virtue of a yeast-two-hybrid screen. SoHo proteins play diverse roles as adaptor proteins in cell signaling, cell adhesion and sarcomere architecture, including altered expression in cancer and FSHD. Specifically, we found SoHo proteins CAP/ponsin-1 and -2 (Sorbs1) and ArgBP2 (Sorbs2) to interact with the cytoplasmic domain of Fat1. We mapped the interaction to a prolin-rich classic type II PXXP motif within Fat1 and to the three Src-homology (SH3) domains within SoHo proteins using mutant expression in yeast, pulldown assays, and cell culture. Functionally, endogenous ponsin-2 expression of NRK-52E cells at cellular leading edges was lost upon knockdown of Fat1. In summary, our data point to an interaction of Fat1 with SoHo proteins that is able to recruit SoHo proteins to sites of Fat1 expression. PMID- 26903300 TI - AKT-p53 axis protect cancer cells from autophagic cell death during nutrition deprivation. AB - An altered metabolism supports growth of tumor. AKT, a major signal integrator plays a key role in cell metabolism. We have shown that nutritional deprivation activates AKT as observed by increased phosphorylation of both Thr308 and Ser473. Pharmacological inhibition or silencing of AKT by siRNA affects cell viability during starvation. The tumor suppressor, p53 is also observed to be elevated during nutritional deprivation due to AKT. Silencing of AKT and p53 enhanced autophagy as evidenced by increased acidic vesicular organelles and LC3B II levels, suggesting AKT-p53 to play a significant role in cell survival through regulating autophagy during nutritional deprivation. PMID- 26903301 TI - Dynamin-related protein inhibitor downregulates reactive oxygen species levels to indirectly suppress high glucose-induced hyperproliferation of vascular smooth muscle cells. AB - Hyperproliferation of vascular smooth muscle cells is a pathogenic mechanism common in diabetic vascular complications and is a putatively important therapeutic target. This study investigated multiple levels of biology, including cellular and organellar changes, as well as perturbations in protein synthesis and morphology. Quantitative and qualitative analysis was utilized to assess the effect of mitochondrial dynamic changes and reactive oxygen species(ROS) levels on high-glucose-induced hyperproliferation of vascular smooth muscle cells. The data demonstrated that the mitochondrial fission inhibitor Mdivi-1 and downregulation of ROS levels both effectively inhibited the high-glucose-induced hyperproliferation of vascular smooth muscle cells. Downregulation of ROS levels played a more direct role and ROS levels were also regulated by mitochondrial dynamics. Increased ROS levels induced excessive mitochondrial fission through dynamin-related protein (Drp 1), while Mdivi-1 suppressed the sensitivity of Drp1 to ROS levels, thus inhibiting excessive mitochondrial fission under high-glucose conditions. This study is the first to propose that mitochondrial dynamic changes and ROS levels interact with each other and regulate high-glucose-induced hyperproliferation of vascular smooth muscle cells. This finding provides novel ideas in understanding the pathogenesis of diabetic vascular remodeling and intervention. PMID- 26903302 TI - Mechanism of extraordinary DNA digestion by pepsin. AB - Recently, the protein-specific enzyme pepsin was found be capable of digesting nucleic acids unexpectedly. In this study, the effects of DNA sequence specificity, purine content (AG content), depurination and length on the nucleic acid (NA) digestion by pepsin were investigated. The results showed that pepsin functioned similar as endonuclease, and presented a moderate sequence preference compared with restriction enzymes and non-specific nuclease. The digestion was specific (sequence dependent to some extent), and pepsin preferred to cleave purine-rich sequences. The digestion of favorable sequence was dramatically accelerated when the purine base at the cleavage site was removed (created an apurinic (AP) site). However, the AP site did not help to cleave the sequence that pepsin could not cleave originally. Moreover, the results indicated that pepsin preferred to digest longer DNA (e.g. > 59 bases) than shorter one, and sequence shorter than 30 bases was barely digested. The mechanism of DNA digestion by pepsin was also discussed. PMID- 26903303 TI - Prospective, Randomized, Double-Blind, Parallel-Group, Comparative Effectiveness Clinical Trial Comparing a Powder Vehicle Compound of Vitamin D With an Oil Vehicle Compound in Adults With Cystic Fibrosis. AB - BACKGROUND: There is little consensus on the most efficacious vehicle substance for vitamin D supplements. Fat malabsorption may impede the ability of patients with cystic fibrosis (CF) to absorb vitamin D in an oil vehicle. We hypothesized that vitamin D contained in a powder vehicle would be absorbed more efficiently than vitamin D contained in an oil vehicle in patients with CF. METHODS: In this double-blind, randomized controlled trial, hospitalized adults with CF were given a one-time bolus dose of 100,000 IU of cholecalciferol (D3) in a powder-based or oil-based vehicle. Serum D3, 25-hydroxyvitamin D, and parathyroid hormone concentrations were analyzed at 0, 12, 24, and 48 hours posttreatment. The area under the curve for serum D3 and the 12-hour time point were also assessed as indicators of D3 absorption. RESULTS: This trial was completed by 15 patients with CF. The median (interquartile range) age, body mass index, and forced expiratory volume in 1 second were 23.7 (19.9-33.2) years, 19.9 (18.6-22.6) kg/m2, and 63% (37%-80%), respectively. The increase in serum D3 and the area under the curve was greater in the powder group ( P = .002 and P = .036, respectively). Serum D3 was higher at 12 hours in the powder group compared with the oil group ( P = .002), although levels were similar between groups by 48 hours. CONCLUSIONS: In adults with CF, cholecalciferol is more efficiently absorbed in a powder compared with an oil vehicle. Physicians should consider prescribing vitamin D in a powder vehicle in patients with CF to improve the absorption of vitamin D from supplements. PMID- 26903304 TI - Human Milk for Ill and Medically Compromised Infants: Strategies and Ongoing Innovation. AB - The use of human milk (mother's own milk and/or donor milk) in ill or medically compromised infants frequently requires some adaptation to address medical diagnoses and/or altered nutrition requirements. This tutorial describes the nutrition and immunological benefits of breast milk as well as provides evidence for the use of donor milk when mother's own milk is unavailable. Several strategies used to modify human milk to meet the medical and nutrition needs of an ill or medically compromised infant are reviewed. These strategies include (1) the standard fortification of human milk to support adequate growth, (2) the novel concept of target fortification in preterm infants, (3) instructions on how to alter maternal diet to address cow's milk protein intolerance and/or allergy in breast milk-fed infants, and (4) the removal and modification of the fat in breast milk used in infants diagnosed with chylothorax. PMID- 26903305 TI - Safety of Bioelectrical Impedance Analysis in Patients Equipped With Implantable Cardioverter Defibrillators. AB - BACKGROUND: Current guidelines warn of potential electromagnetic interferences (EMI) when using bioelectrical impedance analysis (BIA) to measure body composition in patients equipped with implantable cardioverter-defibrillators (ICDs). We aimed to test the occurrence of EMI in a setting where this risk was experimentally maximized. MATERIALS AND METHODS: Outpatients scheduled for routine ICD controls simultaneously underwent a BIA measurement using an electrical current of 0.8 mAmp at frequencies from 5-100 kHz. ICD sensitivity levels were set to maximum levels while therapies were temporarily inactivated. The device electrograms were monitored in real time to detect sensed and/or visible EMI during BIA measurement. RESULTS: A total of 63 patients equipped with single-chamber (n = 13), dual-chamber (n = 18), or biventricular (n = 32) ICDs from 5 major manufacturers were included. No EMI were detected by the ICDs in these patients, nor were any artifacts visualized during real-time electrogram recordings. CONCLUSION: BIA can be safely performed in patients equipped with ICDs without cardiac monitoring. Current guidelines should be updated accordingly. PMID- 26903306 TI - JPEN Journal Club 20. Confirmation Bias. PMID- 26903307 TI - Functional Tricuspid Stenosis in Primary Sclerosing Cholangitis: A Case Report. PMID- 26903310 TI - Photonic biosensor based on photocorrosion of GaAs/AlGaAs quantum heterostructures for detection of Legionella pneumophila. AB - Photocorrosion of semiconductors is strongly sensitive to the presence of surface states, and it could be influenced by electrically charged molecules immobilized near the semiconductor/electrolyte interface. The underlying mechanism is related to band bending of the semiconductor structure near the surface and the associated distribution of excited electrons and holes. The authors have employed photoluminescence of GaAs/AlGaAs quantum heterostructures for monitoring in situ the photocorrosion effect, and demonstrating detection of nongrowing Legionella pneumophila suspended in phosphate buffered saline solution. Antibody functionalized samples allowed direct detection of these bacteria at 10(4) bacteria/ml. The authors discuss the sensitivity of the process related to the ability of creating conditions suitable for photocorrosion proceeding at extremely slow rates and the interaction of an electric charge of bacteria with the surface of a biofunctionalized semiconductor. PMID- 26903309 TI - Slippery when sticky: Lubricating properties of thin films of Taxus baccata aril mucilage. AB - Mucilage is hydrogel produced from succulent plants and microorganisms displaying unique adhesiveness and slipperiness simultaneously. The objective of this study is to establish an understanding on the lubricating mechanisms of the mucilage from Taxus baccata aril as thin, viscous lubricant films. Oscillation and flow rheological studies revealed that T. baccata mucilage is shear-thinning, thixotropic, and weak hydrogel that is highly stretchable under shear stress due to its high density physical crosslinking characteristics. In addition, T. baccata mucilage showed a distinct Weissenberg effect, i.e., increasing normal force with increasing shear rate, and thus it contributes to deplete the lubricant from tribological interfaces. Lubrication studies with a number of tribopairs with varying mechanical properties and surface wettability have shown that the lubricity of T. baccata mucilage is most effectively manifested at soft, hydrophilic, and rolling tribological contacts. Based on tenacious spreading on highly wetting surfaces, slip plane can be formed within mucilage hydrogel network even when the lubricating films cannot completely separate the opposing surfaces. Moreover, highly stretchable characteristics of mucilage under high shear enhance smooth shearing of two opposing surfaces as lubricating film. PMID- 26903308 TI - Susceptibility of outer hair cells to cholesterol chelator 2-hydroxypropyl-beta cyclodextrine is prestin-dependent. AB - Niemann-Pick type C1 disease (NPC1) is a fatal genetic disorder caused by impaired intracellular cholesterol trafficking. Recent studies reported ototoxicity of 2-hydroxypropyl- beta-cyclodextrin (HPbetaCD), a cholesterol chelator and the only promising treatment for NPC1. Because outer hair cells (OHCs) are the only cochlear cells affected by HPbetaCD, we investigated whether prestin, an OHC-specific motor protein, might be involved. Single, high-dose administration of HPbetaCD resulted in OHC death in prestin wildtype (WT) mice whereas OHCs were largely spared in prestin knockout (KO) mice in the basal region, implicating prestin's involvement in ototoxicity of HPbetaCD. We found that prestin can interact with cholesterol in vitro, suggesting that HPbetaCD induced ototoxicity may involve disruption of this interaction. Time-lapse analysis revealed that OHCs isolated from WT animals rapidly deteriorated upon HPbetaCD treatment while those from prestin-KOs tolerated the same regimen. These results suggest that a prestin-dependent mechanism contributes to HPbetaCD ototoxicity. PMID- 26903311 TI - A phase I trial of panobinostat and epirubicin in solid tumors with a dose expansion in patients with sarcoma. AB - BACKGROUND: Treatment options for sarcoma are limited. Histone deacetylase inhibitors increase the efficacy of topoisomerase II inhibitors by promoting access to chromatin and by down-regulating DNA repair. Thus, combined panobinostat and epirubicin therapy was evaluated to treat refractory sarcoma. PATIENTS AND METHODS: Patients with advanced solid tumors were enrolled in a 3 + 3 dose-escalation phase I trial of panobinostat given on days 1, 3, and 5 followed by 75 mg/m(2) of epirubicin on day 5 in 21-day cycles, with a dose expansion at maximum tolerated dose (MTD) in 20 sarcoma patients. Peripheral blood mononucleocyte histone acetylation was also evaluated. RESULTS: Forty patients received 20-60 mg panobinostat. Dose-limiting toxicities included thrombocytopenia, febrile neutropenia, and fatigue at 60 mg, defining a panobinostat MTD at 50 mg. Four responses were seen in 37 assessable patients, all after progression on prior topoisomerase II inhibitors. For those with sarcoma, 12 of 20 derived clinical benefit (1 partial response and 11 stable disease, median overall survival 8.3 months), including 8 of 14 previously progressed on topoisomerase II therapy. Treatment benefits correlated with increased histone acetylation and decreased neutrophil count on day 5. CONCLUSIONS: Panobinostat and epirubicin treatment is well tolerated and may reverse anthracycline resistance. Changes in histone acetylation and associated decrease in neutrophil count correlated with clinical benefit and warrant investigation as predictive biomarkers. CLINICAL TRIAL: This trial is registered at www.Clinicaltrials.gov, Identifier: NCT00878904. PMID- 26903312 TI - Toxin distribution and sphingoid base imbalances in Fusarium verticillioides infected and fumonisin B1-watered maize seedlings. AB - Fusarium verticillioides is a major maize pathogen and there are susceptible and resistant cultivars to this fungal infection. Recent studies suggest that its main mycotoxin fumonisin B1 (FB1) may be involved in phytopathogenicity, but the underlying mechanisms are mostly still unknown. This work was aimed at assessing whether FB1 disseminates inside the plants, as well as identifying possible correlations between the maize resistant/susceptible phenotype and the unbalances of the FB1-structurally-related sphingoid base sphinganine (Sa) and phytosphingosine (Pso) due to toxin accumulation. Resistant (RH) and susceptible hybrid (SH) maize seedlings grown from seeds inoculated with a FB1-producer F. verticillioides and from uninoculated ones irrigated with FB1 (20 ppm), were harvested at 7, 14 and 21 days after planting (dap), and the FB1, Sa and Pso levels were quantified in roots and aerial parts. The toxin was detected in roots and aerial parts for inoculated and FB1-irrigated plants of both hybrids. However, FB1 levels were overall higher in SH seedlings regardless of the treatment (infection or watering). Sa levels increased substantially in RH lines, peaking at 54-fold in infected roots at 14 dap. In contrast, the main change observed in SH seedlings was an increase of Pso in infected roots at 7 dap. Here, it was found that FB1 disseminates inside seedlings in the absence of FB1 producer fungal infections, perhaps indicating this might condition the fungus plant interaction before the first contact. Furthermore, the results strongly suggest the existence of at least two ceramide synthase isoforms in maize with different substrate specificities, whose differential expression after FB1 exposure could be closely related to the susceptibility/resistance to F. verticillioides. PMID- 26903313 TI - Square planar Cu(I) stabilized by a pyridinediimine ligand. AB - A set of distorted square planar Cu(I) complexes were synthesized and characterized utilizing the sterically encumbering pyridinediimine ligand, (iPr)PDI (where (iPr)PDI = 2,6-(2,6-(i)Pr2C6H3N=CMe)2C5H3N). The oxidation state of the Cu center(s) were elucidated to be Cu(I) with a neutral PDI ligand system based on structural, spectroscopic, and computational data. PMID- 26903314 TI - Antimicrobial activity of a quaternary ammonium methacryloxy silicate-containing acrylic resin: a randomised clinical trial. AB - Quaternary ammonium methacryloxy silicate (QAMS)-containing acrylic resin demonstrated contact-killing antimicrobial ability in vitro after three months of water storage. The objective of the present double-blind randomised clinical trial was to determine the in vivo antimicrobial efficacy of QAMS-containing orthodontic acrylic by using custom-made removable retainers that were worn intraorally by 32 human subjects to create 48-hour multi-species plaque biofilms, using a split-mouth study design. Two control QAMS-free acrylic disks were inserted into the wells on one side of an orthodontic retainer, and two experimental QAMS-containing acrylic disks were inserted into the wells on the other side of the same retainer. After 48 hours, the disks were retrieved and examined for microbial vitality using confocal laser scanning microscopy. No harm to the oral mucosa or systemic health occurred. In the absence of carry-across effect and allocation bias (disks inserted in the left or right side of retainer), significant difference was identified between the percentage kill in the biovolume of QAMS-free control disks (3.73 +/- 2.11%) and QAMS-containing experimental disks (33.94 +/- 23.88%) retrieved from the subjects (P <= 0.001). The results validated that the QAMS-containing acrylic exhibits favourable antimicrobial activity against plaque biofilms in vivo. The QAMS-containing acrylic may also be used for fabricating removable acrylic dentures. PMID- 26903318 TI - Spine Patch: Warrington Colescott. PMID- 26903315 TI - Proteome-wide Lysine Glutarylation Profiling of the Mycobacterium tuberculosis H37Rv. AB - Lysine glutarylation, a new protein posttranslational modification (PTM), was recently identified and characterized in both prokaryotic and eukaryotic cells. To explore the distribution of lysine glutarylation in Mycobacterium tuberculsosis, by using a comprehensive method combining the immune affinity peptide enrichment by the glutaryl-lysine antibody with LC-MS, we finally identified 41 glutarylation sites in 24 glutarylated proteins from M. tuberculosis. These glutarylated proteins are involved in various cellular functions such as translation and metabolism and exhibit diverse subcellular localizations. Three common glutarylated proteins including 50S ribosomal protein L7/L12, elongation factor Tu, and dihydrolipoamide succinyltransferase are shared between Escherichia coli and M. tuberculosis. Moreover, comparison with other PTMs characterized in M. tuberculosis, 15 glutarylated proteins, are found to be both acetylated and succinylated. Notably, several stress-response-associated proteins including HspX are glutarylated. Our data provide the first analysis of M. tuberculosis lysine glutarylated proteins. Further studies on the role of the glutarylated proteins will unveil the molecular mechanisms of glutarylation underlying M. tuberculosis physiology and pathogenesis. PMID- 26903319 TI - New Sepsis Diagnostic Guidelines Shift Focus to Organ Dysfunction. PMID- 26903328 TI - New Strategies for Effective Therapeutics in Critically Ill Patients. PMID- 26903329 TI - Critical Care and the Brain. PMID- 26903330 TI - Organizing Critical Care for the 21st Century. PMID- 26903331 TI - Critical Care in Resource-Restricted Settings. PMID- 26903332 TI - A PIECE OF MY MIND. What Now? What Next? PMID- 26903333 TI - New Definitions for Sepsis and Septic Shock: Continuing Evolution but With Much Still to Be Done. PMID- 26903334 TI - The Acute Respiratory Distress Syndrome: Dialing in the Evidence? PMID- 26903335 TI - Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). AB - IMPORTANCE: The Third International Consensus Definitions Task Force defined sepsis as "life-threatening organ dysfunction due to a dysregulated host response to infection." The performance of clinical criteria for this sepsis definition is unknown. OBJECTIVE: To evaluate the validity of clinical criteria to identify patients with suspected infection who are at risk of sepsis. DESIGN, SETTINGS, AND POPULATION: Among 1.3 million electronic health record encounters from January 1, 2010, to December 31, 2012, at 12 hospitals in southwestern Pennsylvania, we identified those with suspected infection in whom to compare criteria. Confirmatory analyses were performed in 4 data sets of 706,399 out-of hospital and hospital encounters at 165 US and non-US hospitals ranging from January 1, 2008, until December 31, 2013. EXPOSURES: Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score, systemic inflammatory response syndrome (SIRS) criteria, Logistic Organ Dysfunction System (LODS) score, and a new model derived using multivariable logistic regression in a split sample, the quick Sequential [Sepsis-related] Organ Failure Assessment (qSOFA) score (range, 0-3 points, with 1 point each for systolic hypotension [<=100 mm Hg], tachypnea [>=22/min], or altered mentation). MAIN OUTCOMES AND MEASURES: For construct validity, pairwise agreement was assessed. For predictive validity, the discrimination for outcomes (primary: in-hospital mortality; secondary: in hospital mortality or intensive care unit [ICU] length of stay >=3 days) more common in sepsis than uncomplicated infection was determined. Results were expressed as the fold change in outcome over deciles of baseline risk of death and area under the receiver operating characteristic curve (AUROC). RESULTS: In the primary cohort, 148,907 encounters had suspected infection (n = 74,453 derivation; n = 74,454 validation), of whom 6347 (4%) died. Among ICU encounters in the validation cohort (n = 7932 with suspected infection, of whom 1289 [16%] died), the predictive validity for in-hospital mortality was lower for SIRS (AUROC = 0.64; 95% CI, 0.62-0.66) and qSOFA (AUROC = 0.66; 95% CI, 0.64-0.68) vs SOFA (AUROC = 0.74; 95% CI, 0.73-0.76; P < .001 for both) or LODS (AUROC = 0.75; 95% CI, 0.73-0.76; P < .001 for both). Among non-ICU encounters in the validation cohort (n = 66 522 with suspected infection, of whom 1886 [3%] died), qSOFA had predictive validity (AUROC = 0.81; 95% CI, 0.80-0.82) that was greater than SOFA (AUROC = 0.79; 95% CI, 0.78-0.80; P < .001) and SIRS (AUROC = 0.76; 95% CI, 0.75 0.77; P < .001). Relative to qSOFA scores lower than 2, encounters with qSOFA scores of 2 or higher had a 3- to 14-fold increase in hospital mortality across baseline risk deciles. Findings were similar in external data sets and for the secondary outcome. CONCLUSIONS AND RELEVANCE: Among ICU encounters with suspected infection, the predictive validity for in-hospital mortality of SOFA was not significantly different than the more complex LODS but was statistically greater than SIRS and qSOFA, supporting its use in clinical criteria for sepsis. Among encounters with suspected infection outside of the ICU, the predictive validity for in-hospital mortality of qSOFA was statistically greater than SOFA and SIRS, supporting its use as a prompt to consider possible sepsis. PMID- 26903336 TI - Developing a New Definition and Assessing New Clinical Criteria for Septic Shock: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). AB - IMPORTANCE: Septic shock currently refers to a state of acute circulatory failure associated with infection. Emerging biological insights and reported variation in epidemiology challenge the validity of this definition. OBJECTIVE: To develop a new definition and clinical criteria for identifying septic shock in adults. DESIGN, SETTING, AND PARTICIPANTS: The Society of Critical Care Medicine and the European Society of Intensive Care Medicine convened a task force (19 participants) to revise current sepsis/septic shock definitions. Three sets of studies were conducted: (1) a systematic review and meta-analysis of observational studies in adults published between January 1, 1992, and December 25, 2015, to determine clinical criteria currently reported to identify septic shock and inform the Delphi process; (2) a Delphi study among the task force comprising 3 surveys and discussions of results from the systematic review, surveys, and cohort studies to achieve consensus on a new septic shock definition and clinical criteria; and (3) cohort studies to test variables identified by the Delphi process using Surviving Sepsis Campaign (SSC) (2005-2010; n = 28,150), University of Pittsburgh Medical Center (UPMC) (2010-2012; n = 1,309,025), and Kaiser Permanente Northern California (KPNC) (2009-2013; n = 1,847,165) electronic health record (EHR) data sets. MAIN OUTCOMES AND MEASURES: Evidence for and agreement on septic shock definitions and criteria. RESULTS: The systematic review identified 44 studies reporting septic shock outcomes (total of 166,479 patients) from a total of 92 sepsis epidemiology studies reporting different cutoffs and combinations for blood pressure (BP), fluid resuscitation, vasopressors, serum lactate level, and base deficit to identify septic shock. The septic shock-associated crude mortality was 46.5% (95% CI, 42.7%-50.3%), with significant between-study statistical heterogeneity (I2 = 99.5%; tau2 = 182.5; P < .001). The Delphi process identified hypotension, serum lactate level, and vasopressor therapy as variables to test using cohort studies. Based on these 3 variables alone or in combination, 6 patient groups were generated. Examination of the SSC database demonstrated that the patient group requiring vasopressors to maintain mean BP 65 mm Hg or greater and having a serum lactate level greater than 2 mmol/L (18 mg/dL) after fluid resuscitation had a significantly higher mortality (42.3% [95% CI, 41.2%-43.3%]) in risk-adjusted comparisons with the other 5 groups derived using either serum lactate level greater than 2 mmol/L alone or combinations of hypotension, vasopressors, and serum lactate level 2 mmol/L or lower. These findings were validated in the UPMC and KPNC data sets. CONCLUSIONS AND RELEVANCE: Based on a consensus process using results from a systematic review, surveys, and cohort studies, septic shock is defined as a subset of sepsis in which underlying circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than sepsis alone. Adult patients with septic shock can be identified using the clinical criteria of hypotension requiring vasopressor therapy to maintain mean BP 65 mm Hg or greater and having a serum lactate level greater than 2 mmol/L after adequate fluid resuscitation. PMID- 26903339 TI - Shared Decision Making in Uncomplicated Appendicitis: It Is Time to Include Nonoperative Management. PMID- 26903340 TI - Topical Nonsteroidal Anti-inflammatory Drugs for Acute Musculoskeletal Pain. AB - CLINICAL QUESTION: Are topical nonsteroidal anti-inflammatory drugs (NSAIDs) associated with reduced pain intensity in acute musculoskeletal conditions, but without increased adverse events? BOTTOM LINE: When treating musculoskeletal conditions such as sprains, strains, and contusions, topical NSAIDs are associated with greater pain relief, but are not associated with an increase in adverse events compared with placebo. PMID- 26903341 TI - Histone-Associated Thrombocytopenia in Patients Who Are Critically Ill. PMID- 26903342 TI - School-Based Myopia Prevention Effort. PMID- 26903338 TI - The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis 3). AB - IMPORTANCE: Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination. OBJECTIVE: To evaluate and, as needed, update definitions for sepsis and septic shock. PROCESS: A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epidemiology was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment). KEY FINDINGS FROM EVIDENCE SYNTHESIS: Limitations of previous definitions included an excessive focus on inflammation, the misleading model that sepsis follows a continuum through severe sepsis to shock, and inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple definitions and terminologies are currently in use for sepsis, septic shock, and organ dysfunction, leading to discrepancies in reported incidence and observed mortality. The task force concluded the term severe sepsis was redundant. RECOMMENDATIONS: Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock can be clinically identified by a vasopressor requirement to maintain a mean arterial pressure of 65 mm Hg or greater and serum lactate level greater than 2 mmol/L (>18 mg/dL) in the absence of hypovolemia. This combination is associated with hospital mortality rates greater than 40%. In out-of-hospital, emergency department, or general hospital ward settings, adult patients with suspected infection can be rapidly identified as being more likely to have poor outcomes typical of sepsis if they have at least 2 of the following clinical criteria that together constitute a new bedside clinical score termed quickSOFA (qSOFA): respiratory rate of 22/min or greater, altered mentation, or systolic blood pressure of 100 mm Hg or less. CONCLUSIONS AND RELEVANCE: These updated definitions and clinical criteria should replace previous definitions, offer greater consistency for epidemiologic studies and clinical trials, and facilitate earlier recognition and more timely management of patients with sepsis or at risk of developing sepsis. PMID- 26903343 TI - School-Based Myopia Prevention Effort. PMID- 26903344 TI - School-Based Myopia Prevention Effort--Reply. PMID- 26903345 TI - Differences in Institutional Support by Sex. PMID- 26903346 TI - Differences in Institutional Support by Sex--Reply. PMID- 26903347 TI - Two Incorrect Author Affiliations. PMID- 26903348 TI - Incorrect Version Published. PMID- 26903349 TI - Errors in Text. PMID- 26903351 TI - Postoperative Sepsis. PMID- 26903352 TI - JAMA PATIENT PAGE. Asthma Attacks. PMID- 26903353 TI - DSM-5 and Other Symptom Thresholds for ADHD: Which Is the Best Predictor of Impairment in College Students? AB - OBJECTIVE: Approximately 5% of adults have ADHD. Despite recommendations regarding the diagnosis of emerging adults, there is not a strong consensus regarding the ideal method for diagnosing ADHD in both emerging and mature adults. We were interested in determining whether a threshold of four, five, or six ADHD symptoms would be associated with significantly different levels of functional impairment and be more or less indicative of a potential ADHD diagnosis. METHOD: We examined the relation between functional impairment and these ADHD symptom thresholds in 2,577 college students. RESULTS: Our findings suggest that none of these symptom thresholds are differentially better at predicting functional impairment. CONCLUSION: The Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) threshold of five symptoms for ages 17 years and older is not necessarily predictive of ADHD-related impairment in college students and may not be preferable to other thresholds. Options for resolving this diagnostic dilemma are discussed. PMID- 26903354 TI - Perceived self-efficacy. PMID- 26903356 TI - Canadian data provide window on statin use. PMID- 26903355 TI - Recommendations on screening for colorectal cancer in primary care. PMID- 26903357 TI - Frequent urinary tract infections in a premenopausal woman. PMID- 26903358 TI - Don't automatically label Syrian refugees as mentally ill. PMID- 26903360 TI - Treating fracture of the clavicle. PMID- 26903359 TI - Macrolide antibiotics and the risk of ventricular arrhythmia in older adults. AB - BACKGROUND: Many respiratory tract infections are treated with macrolide antibiotics. Regulatory agencies warn that these antibiotics increase the risk of ventricular arrhythmia. We examined the 30-day risk of ventricular arrhythmia and all-cause mortality associated with macrolide antibiotics relative to nonmacrolide antibiotics. METHODS: We conducted a population-based retrospective cohort study involving older adults (age > 65 yr) with a new prescription for an oral macrolide antibiotic (azithromycin, clarithromycin or erythromycin) in Ontario from 2002 to 2013. Our primary outcome was a hospital encounter with ventricular arrhythmia within 30 days after a new prescription. Our secondary outcome was 30-day all-cause mortality. We matched patients 1:1 using propensity scores to patients prescribed nonmacrolide antibiotics (amoxicillin, cefuroxime or levofloxacin). We used conditional logistic regression to measure the association between macrolide exposure and outcomes, and repeated the analysis in 4 subgroups defined by the presence or absence of chronic kidney disease, congestive heart failure, coronary artery disease and concurrent use of a drug known to prolong the QT interval. RESULTS: Compared with nonmacrolide antibiotics, macrolide antibiotics were not associated with a higher risk of ventricular arrhythmia (0.03% v. 0.03%; relative risk [RR] 1.06, 95% confidence interval [CI] 0.83-1.36) and were associated with a lower risk of all-cause mortality (0.62% v. 0.76%; RR 0.82, 95% CI 0.78-0.86). These associations were similar in all subgroups. INTERPRETATION: Among older adults, macrolide antibiotics were not associated with a higher 30-day risk of ventricular arrhythmia than nonmacrolide antibiotics. These findings suggest that current warnings from the US Food and Drug Administration may be overstated. PMID- 26903361 TI - Hydroxychloroquine-related skin discoloration. PMID- 26903363 TI - Bone regeneration after chemotherapy for vault lymphoma. AB - A 76-year-old woman presented with a mass in the left frontal region of the scalp. On admission, neurological examination found no deficits. CT revealed an osteolytic mass lesion in the left frontal cranial vault. She underwent open biopsy of the subcutaneous lesion. Histological examination identified cells with pleomorphic nuclei and marked nucleoli, and immunohistochemical staining showed these cells were positive for CD20, but negative for CD3. The histological diagnosis was diffuse large B-cell lymphoma. The patient received chemotherapy consisting of rituximab, cyclophosphamide, adriamycin, vincristine and prednisolone. Fluorine-18 fluorodeoxyglucose positron emission tomography demonstrated complete response. Follow-up CT revealed that the tumour had completely disappeared, with regeneration of the destroyed bone. The regenerated skull bone had adequate strength without significant deformity, so cranioplasty was unnecessary. The present case demonstrates the regeneration of destroyed skull bone after chemotherapy for cranial vault lymphoma. PMID- 26903362 TI - Plasma Biomarker Enrichment of Clinical Prognostic Indices in Malignant Pleural Mesothelioma. AB - OBJECTIVES: Prognostic models for malignant pleural mesothelioma (MPM) are needed to prevent potentially futile outcomes. We combined MPM plasma biomarkers with validated clinical prognostic indices to determine whether stratification of risk for death in 194 patients with MPM improved. METHODS: Individuals were recruited from three different centers: a discovery cohort (83 patients with MPM) created by combining patients from two U.S. centers and a separate, independent cohort from Canada (111 patients with MPM). Univariable and multivariable analyses were performed on the initial discovery and independent cohorts separately. In the multivariable analyses, prognostic factors were adjusted for the European Organisation for Research and Treatment of Cancer (EORTC) prognostic index (PI) of mesothelioma. The prognostic significance of adding plasma biomarker data to the PI was determined by using the likelihood ratio test, comparing models with and without the addition of biomarker to the clinical PI. The predictive ability of the biomarker was then assessed formally using Harrell's C-index by applying the fitted model variables of the discovery cohort to the second, independent cohort, including and not including the biomarker with the PI. RESULTS: Higher levels of osteopontin and mesothelin were individually associated with worse prognosis after adjusting for the PI. In the independent cohort, incorporating either plasma osteopontin or mesothelin into the baseline predictive PI model substantively and statistically significantly improved Harrell's C-statistic. In the final prognostic model, log-osteopontin, EORTC clinical prognostic index, and hemoglobin remained as independently significant predictors and the entire prognostic model improved the optimism-corrected Harrell's C-index significantly, from 0.718 (0.67-0.77) to 0.801 (0.77-0.84). CONCLUSIONS: These data suggest a possible role for preoperative plasma biomarkers to improve the prognostic capability of the EORTC PI of MPM. PMID- 26903364 TI - Previously undiagnosed fatal familial haemophagocytic lymphohistiocytosis in a 24 year-old woman. AB - We present a case of a 24-year-old woman with previously undiagnosed familial haemophagocytic lymphohistiocytosis (HLH). The patient presented with fevers and cough and was found to have pancytopaenia. She underwent an extensive work up and initially met only 3 of 8 criteria for HLH. Owing to high clinical suspicion, soluble CD25 level was sent and HLH2004 protocol initiated. The soluble CD25 level returned elevated with other laboratory work and the patient met criteria for diagnosis of HLH. Genetic studies revealed a homozygous mutation in PRF1 with absent perforin in cytotoxic cells, consistent with familial HLH. The patient expired before intrathecal chemotherapy could be initiated. This case illustrates the potential for familial HLH to present at an older age, and highlights the importance of early recognition and initiation of treatment of HLH, as patients may not initially fulfil the diagnostic criteria for HLH, and mortality is high if left untreated. PMID- 26903365 TI - Clostridium difficile ileitis in a patient, after total colectomy. AB - This is a case of a 63-year-old, post total colectomy patient, who presented to the hospital with watery diarrhoea, abdominal cramping and fevers. On admission, the patient was haemodynamically stable and febrile. Clostridium difficile PCR was sent and tested positive. CT of the abdomen revealed diffuse thickening of the distal small bowel to the level of the anastomosis and mesenteric oedema consistent with infectious enteritis. The patient was started on vancomycin orally as well as flagyl intravenously. Because of an ileus, he initially was treated with bowel rest and a NG tube. Surgical consult was obtained early with no intervention. The patient's symptoms progressively resolved over the next 7 days of hospitalisation, and he was discharged home. PMID- 26903366 TI - Rare cause of pancolitis. PMID- 26903367 TI - Antiproliferative activity of a series of cisplatin-based Pt(IV) acetylamido/carboxylato prodrugs. AB - We report studies of a novel series of Pt(IV) complexes exhibiting an asymmetric combination of acetylamido and carboxylato ligands in the axial positions. We demonstrate efficient synthesis of a series of analogues, differing in the alkyl chain length and hence lipophilicity, from a stable acetylamido/hydroxido complex formed by reaction of cisplatin with peroxyacetimidic acid (PAIA). NMR spectroscopy and X-ray crystallography confirm the identity of the resulting complexes, and highlight subtle differences in the structure and stability of acetylamido complexes compared to the equivalent acetato complexes. Reduction of acetylamido complexes, whether achieved chemically or electro-chemically, is significantly more difficult than that of acetate complexes, resulting in lower antiproliferative activity for shorter-chain complexes. For those with longer chains and hence greater cell uptake, this difference is negated and acetylamido complexes are as active as acetato analogues, both exhibiting antiproliferative potency (1/IC50) against A2780 ovarian cancer cells similar to that of cisplatin. PMID- 26903337 TI - Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries. AB - IMPORTANCE: Limited information exists about the epidemiology, recognition, management, and outcomes of patients with the acute respiratory distress syndrome (ARDS). OBJECTIVES: To evaluate intensive care unit (ICU) incidence and outcome of ARDS and to assess clinician recognition, ventilation management, and use of adjuncts-for example prone positioning-in routine clinical practice for patients fulfilling the ARDS Berlin Definition. DESIGN, SETTING, AND PARTICIPANTS: The Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) was an international, multicenter, prospective cohort study of patients undergoing invasive or noninvasive ventilation, conducted during 4 consecutive weeks in the winter of 2014 in a convenience sample of 459 ICUs from 50 countries across 5 continents. EXPOSURES: Acute respiratory distress syndrome. MAIN OUTCOMES AND MEASURES: The primary outcome was ICU incidence of ARDS. Secondary outcomes included assessment of clinician recognition of ARDS, the application of ventilatory management, the use of adjunctive interventions in routine clinical practice, and clinical outcomes from ARDS. RESULTS: Of 29,144 patients admitted to participating ICUs, 3022 (10.4%) fulfilled ARDS criteria. Of these, 2377 patients developed ARDS in the first 48 hours and whose respiratory failure was managed with invasive mechanical ventilation. The period prevalence of mild ARDS was 30.0% (95% CI, 28.2%-31.9%); of moderate ARDS, 46.6% (95% CI, 44.5%-48.6%); and of severe ARDS, 23.4% (95% CI, 21.7%-25.2%). ARDS represented 0.42 cases per ICU bed over 4 weeks and represented 10.4% (95% CI, 10.0%-10.7%) of ICU admissions and 23.4% of patients requiring mechanical ventilation. Clinical recognition of ARDS ranged from 51.3% (95% CI, 47.5%-55.0%) in mild to 78.5% (95% CI, 74.8%-81.8%) in severe ARDS. Less than two-thirds of patients with ARDS received a tidal volume 8 of mL/kg or less of predicted body weight. Plateau pressure was measured in 40.1% (95% CI, 38.2 42.1), whereas 82.6% (95% CI, 81.0%-84.1%) received a positive end-expository pressure (PEEP) of less than 12 cm H2O. Prone positioning was used in 16.3% (95% CI, 13.7%-19.2%) of patients with severe ARDS. Clinician recognition of ARDS was associated with higher PEEP, greater use of neuromuscular blockade, and prone positioning. Hospital mortality was 34.9% (95% CI, 31.4%-38.5%) for those with mild, 40.3% (95% CI, 37.4%-43.3%) for those with moderate, and 46.1% (95% CI, 41.9%-50.4%) for those with severe ARDS. CONCLUSIONS AND RELEVANCE: Among ICUs in 50 countries, the period prevalence of ARDS was 10.4% of ICU admissions. This syndrome appeared to be underrecognized and undertreated and associated with a high mortality rate. These findings indicate the potential for improvement in the management of patients with ARDS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02010073. PMID- 26903369 TI - Responses of Soil Fungal Populations and Communities to the Thinning of Cryptomeria Japonica Forests. AB - Forest management activities, such as tree thinning, alter forest ecology, including key components of forest ecosystems, including fungal communities. In the present study, we investigate the effects of forest thinning intensity on the populations and structures of fungal soil communities in the Cryptomeria japonica forests of central Taiwan as well as the dynamics of soil fungi communities in these forests after a thinning disturbance. Although the populations of soil fungi significantly increased in the first 6 months after thinning, these increases had subsided by 9 months. This pulse was attributed to a transient increase in the populations of rapid colonizers. A multiple regression analysis positively correlated fungal populations with organic matter content and cellulase activity. Thinning initially provided large amounts of fresh leaves and roots as nutrient-rich substrates for soil fungi. Denaturing gradient gel electrophoresis (DGGE) profiles indicated that soil fungal communities significantly differed among plots with 0% (control), 25%, and 50% tree thinning in the first 21 months post-thinning, with no significant differences being observed after 21 months. The fungal communities of these forest soils also changed with the seasons, and an interactive relationship was detected between seasons and treatments. Seasonal variations in fungal communities were the most pronounced after 50% tree thinning. The results of the present study demonstrate that the soil fungi of Taiwanese C. japonica forests are very sensitive to thinning disturbances, but recover stability after a relatively short period of time. PMID- 26903368 TI - Impact of Arsenite on the Bacterial Community Structure and Diversity in Soil. AB - The impact of arsenite (As[III]) on the bacterial community structure and diversity in soil was determined by incubating soil slurries with 50, 500, and 5,000 MUM As(III). As(III) was oxidized to arsenate (As[V]), and the microbial contribution to As(III) oxidation was 70-100%. PCR-denaturing gradient gel electrophoresis revealed that soil bacterial diversity decreased in the presence of As(III). Bacteria closely related to the family Bacillaceae were predominant in slurry spiked with 5,000 MUM As(III). The population size of culturable As(III)-resistant bacteria was 37-fold higher in this slurry than in unspiked slurry (p < 0.01), indicating that high levels of As(III) stimulate the emergence of As(III)-resistant bacteria. As(III)-resistant bacteria isolated from slurry spiked with 5,000 MUM As(III) were mainly affiliated with the genus Bacillus; however, no strains showed As(III)-oxidizing capacity. An As(III)-oxidizing bacterial community analysis based on As(III) oxidase gene (aioA) sequences demonstrated that diversity was the lowest in slurry spiked with 5,000 MUM As(III). The deduced AioA sequences affiliated with Alphaproteobacteria accounted for 91-93% of all sequences in this slurry, among which those closely related to Bosea spp. were predominant (48-86%). These results suggest that exposure to high levels of As(III) has a significant impact on the composition and diversity of the soil bacterial community, including the As(III)-oxidizing bacterial community. Certain As(III)-oxidizing bacteria with strong As(III) resistance may be enriched under high As(III) levels, while more sensitive As(III) oxidizers are eliminated under these conditions. PMID- 26903371 TI - Studies on Animals and the Rise of Comparative Anatomy at and around the Parisian Royal Academy of Sciences in the Eighteenth Century. AB - Argument This paper aims to understand the emergence of comparative anatomy in the eighteenth century in the Parisian Academie Royale des Sciences. As early as the 1670s, a program centered on animal anatomy was conceived, which was a first attempt to give some autonomy to studies on animals and to link anatomy with natural history, but it declined after 1690. However, a variety of studies on animals was published in the Memoires of the Academie during the eighteenth century. We propose a descriptive typology of them in order to explore the status of animals and the significance of anatomy in each type, and to determine, in particular, which elements of Perrault's program were passed on at the Academie throughout the century. We discuss the influence of this legacy on the development of comparative anatomy after 1750, especially in Daubenton's work. PMID- 26903370 TI - On Some Issues of Human-Animal Studies: An Introduction. AB - Animals are "in" - since prehistoric times when humans (or their ancient ancestors) were hunting animals, and when they fabricated the Paleolithic dog as well as the Paleolithic cat. In less general terms, animals are "in" since they received names and were listed, observed, mummified, turned into totems, and, later on, dissected, tortured under laboratory conditions, trained as experimental subjects or "purified" as model organisms. And they are massively "in" again, but now from overtly legal and moral points of view, at least since the last two decades of the twentieth century. This is to say that modern members of the species Homo sapiens have always been connected to animals of the most various kinds - from the human flea (Pulex irritans) and the cat flea (Ctenocephalides felis) to marine mammals, such as dolphins and whales, from horses to parrots, from scallops to worms, and so on. PMID- 26903372 TI - The Receding Animal: Theorizing Anxiety and Attachment in Psychoanalysis from Freud to Imre Hermann. AB - Argument Animals played an important role in the formation of psychoanalysis as a theoretical and therapeutic enterprise. They are at the core of texts such as Freud's famous case histories of Little Hans, the Rat Man, or the Wolf Man. The infantile anxiety triggered by animals provided the essential link between the psychology of individual neuroses and the ambivalent status of the "totem" animal in so-called primitive societies in Freud's attempt to construct an anthropological basis for the Oedipus complex in Totem and Taboo. In the following, we attempt to track the status of animals as objects of indirect observation as they appear in Freud's classical texts, and in later revisionist accounts such as Otto Rank's Trauma of Birth and Imre Hermann's work on the clinging instinct. In the 1920s and 1930s, the Freudian conception of patients' animal phobias is substantially revised within Hermann's original psychoanalytic theory of instincts which draws heavily upon ethological observations of primates. Although such a reformulation remains grounded in the idea of "archaic" animal models for human development, it allows to a certain extent to empiricize the speculative elements of Freud's later instinct theory (notably the death instinct) and to come to a more embodied account of psychoanalytic practice. PMID- 26903373 TI - Cats on the Couch: The Experimental Production of Animal Neurosis. AB - Argument In the 1940s-50s, one of the most central questions in psychological research related to the nature of neurosis. In the final years of the Second World War and the following decade, neurosis became one of the most prominent psychiatric disorders, afflicting a high proportion of military casualties and veterans. The condition became central to the concerns of several psychological fields, from psychoanalysis to Pavlovian psychology. This paper reconstructs the efforts of Chicago psychiatrist Jules Masserman to study neurosis in the laboratory during the 1940s and 1950s. Masserman used Pavlovian techniques in a bid to subject this central psychoanalytic subject to disciplined scientific experimentation. More generally, his project was an effort to bolster the legitimacy of psychoanalysis as a human science by articulating a convergence of psychoanalytic categories across multiple species. Masserman sought to orchestrate a convergence of psychological knowledge between fields that were often taken to be irreconcilable. A central focus of this paper is the role of moving images in this project, not only as a means of recording experimental data but also as a rhetorical device. The paper argues that for Masserman film played an important role in enabling scientific observers (and then subsequent viewers) to see agency and emotion in the animals they observed. PMID- 26903374 TI - Naming the Ethological Subject. AB - Argument In recent decades, through the work of Jane Goodall and other ethologists, the practice of giving personal names to nonhuman animals who are the subjects of scientific research has become associated with claims about animal personhood and scientific objectivity. While critics argue that such naming practices predispose the researcher toward anthropomorphism, supporters suggest that it sensitizes the researcher to individual differences and social relations. Both critics and supporters agree that naming tends to be associated with the recognition of individual animal rights. The history of the naming of research animals since the late nineteenth century shows, however, that the practice has served a variety of purposes, most of which have raised few ethical or epistemological concerns. Names have been used to identify research animals who play dual roles as pets, workers, or patients, to enhance their market value, and to facilitate their identification in the field. The multifaceted history of naming suggests both that the use of personal names by Goodall and others is less of a radical break with previous practices than it might first appear to be and that the use of personal names to recognize the individuality, sentience, or rights of nonhuman animals faces inherent limits and contradictions. PMID- 26903375 TI - Endothelial nitric oxide synthase gene polymorphisms and the risk of vasculopathy in sickle cell disease. AB - BACKGROUND: Sickle cell disease (SCD) is one of the major health problems in many parts of the world. SCD is characterized by multisystem complications with marked variability in its severity between patients, probably linked to nitric oxide (NO). Endothelial nitric oxide synthase (eNOS) enzyme which is responsible for NO synthesis may be implicated in SCD pathophysiology. AIM OF THE STUDY: To explore the possible association between the eNOS gene polymorphisms and severity of SCD. Furthermore, we examined the genomic diversity of these polymorphisms in SCD patients. METHODS: We genotyped 100 SCD patients and 80 controls were genotyped for eNOS 4a/b and eNOS 786T>C polymorphisms, using allele-specific polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism assay, respectively. Polymorphisms were analyzed in relation to severity of SCD manifestations. RESULTS: The homozygous mutant eNOS-786T>T genotype was significantly associated with high risk of acute chest syndrome (ACS). The wild type eNOS-4a/4b genotype was protective against vaso-occlusive crisis (VOC) and pulmonary hypertension (PHTN). The mutant homozygous haplotype (C -4a) was significantly associated with the risk of ACS, VOC, and PHTN. CONCLUSION: eNOS intron 4 and eNOS T>C gene polymorphisms may be used as a genetic marker of prognostic value in SCD, as they are associated with unfavorable clinical outcomes. PMID- 26903376 TI - Argonaute 2-dependent Regulation of Gene Expression by Single-stranded miRNA Mimics. AB - MicroRNAs (miRNAs) are small noncoding transcripts that regulate gene expression. Aberrant expression of miRNAs can affect development of cancer and other diseases. Synthetic miRNA mimics can modulate gene expression and offer an approach to therapy. Inside cells, mature miRNAs are produced as double-stranded RNAs and miRNA mimics typically retain both strands. This need for two strands has the potential to complicate drug development. Recently, synthetic chemically modified single-stranded silencing RNAs (ss-siRNA) have been shown to function through the RNAi pathway to induce gene silencing in cell culture and animals. Here, we test the hypothesis that single-stranded miRNA (ss-miRNA) can also mimic the function of miRNAs. We show that ss-miRNAs can act as miRNA mimics to silence the expression of target genes. Gene silencing requires expression of argonaute 2 (AGO2) protein and involves recruitment of AGO2 to the target transcripts. Chemically modified ss-miRNAs function effectively inside cells through endogenous RNAi pathways and broaden the options for miRNA-based oligonucleotide drug development. PMID- 26903378 TI - Thalidomide-induced limb abnormalities in a humanized CYP3A mouse model. AB - Thalidomide is a teratogen in humans but not in rodents. It causes multiple birth defects including malformations of limbs, ears, and other organs. However, the species-specific mechanism of thalidomide teratogenicity is not completely understood. Reproduction of the human teratogenicity of thalidomide in rodents has previously failed because of the lack of a model reflecting human drug metabolism. In addition, because the maternal metabolic effect cannot be eliminated, the migration of unchanged thalidomide to embryos is suppressed, and the metabolic activation is insufficient to develop teratogenicity. Previously, we generated transchromosomic mice containing a human cytochrome P450 (CYP) 3A cluster in which the endogenous mouse Cyp3a genes were deleted. Here, we determined whether human CYP3A or mouse Cyp3a enzyme expression was related to the species difference in a whole embryo culture system using humanized CYP3A mouse embryos. Thalidomide-treated embryos with the human CYP3A gene cluster showed limb abnormalities, and human CYP3A was expressed in the placenta, suggesting that human CYP3A in the placenta may contribute to the teratogenicity of thalidomide. These data suggest that the humanized CYP3A mouse is a useful model to predict embryonic toxicity in humans. PMID- 26903379 TI - Hosting an Unruly Guest: The Impact of Late Acute and Chronic Graft-versus-Host Disease. PMID- 26903377 TI - Cardiac sodium channel regulator MOG1 regulates cardiac morphogenesis and rhythm. AB - MOG1 was initially identified as a protein that interacts with the small GTPase Ran involved in transport of macromolecules into and out of the nucleus. In addition, we have established that MOG1 interacts with the cardiac sodium channel Nav1.5 and regulates cell surface trafficking of Nav1.5. Here we used zebrafish as a model system to study the in vivo physiological role of MOG1. Knockdown of mog1 expression in zebrafish embryos significantly decreased the heart rate (HR). Consistently, the HR increases in embryos with over-expression of human MOG1. Compared with wild type MOG1 or control EGFP, mutant MOG1 with mutation E83D associated with Brugada syndrome significantly decreases the HR. Interestingly, knockdown of mog1 resulted in abnormal cardiac looping during embryogenesis. Mechanistically, knockdown of mog1 decreases expression of hcn4 involved in the regulation of the HR, and reduces expression of nkx2.5, gata4 and hand2 involved in cardiac morphogenesis. These data for the first time revealed a novel role that MOG1, a nucleocytoplasmic transport protein, plays in cardiac physiology and development. PMID- 26903380 TI - Allogeneic Hematopoietic Cell Transplantation for Patients with Mixed Phenotype Acute Leukemia. AB - Acute biphenotypic leukemias or mixed phenotype acute leukemias (MPAL) are rare and considered high risk. The optimal treatment and the role of allogeneic hematopoietic stem cell transplantation (alloHCT) are unclear. Most prior case series include only modest numbers of patients who underwent transplantation. We analyzed the outcome of 95 carefully characterized alloHCT patients with MPAL reported to the Center for International Blood and Marrow Transplant Research between 1996 and 2012. The median age was 20 years (range, 1 to 68). Among the 95 patients, 78 were in first complete remission (CR1) and 17 were in second complete remission (CR2). Three-year overall survival (OS) of 67% (95% confidence interval [CI], 57 to 76), leukemia-free survival of 56% (95% CI, 46 to 66), relapse incidence of 29% (95% CI, 20 to 38), and nonrelapse mortality of 15% (95% CI, 9 to 23) were encouraging. OS was best in younger patients (<20 years), but no significant differences were observed between those 20 to 40 years of age and those who were 40 years or older. A matched-pair analysis showed similar outcomes comparing MPAL cases to 375 acute myelogenous leukemia or 359 acute lymphoblastic leukemia cases. MPAL patients had more acute and a trend for more chronic graft versus-host disease. No difference was observed between patients who underwent transplantation in CR1 versus those who underwent transplantation in CR2. AlloHCT is a promising treatment option for pediatric and adult patients with MPAL with encouraging long-term survival. PMID- 26903381 TI - End-of-Life Care Patterns Associated with Pediatric Palliative Care among Children Who Underwent Hematopoietic Stem Cell Transplant. AB - Stem cell transplantation (SCT) is an intensive therapy offering the possibility of cure for life-threatening conditions but with risk of serious complications and death. Outcomes associated with pediatric palliative care (PPC) for children who undergo SCT are unknown. Therefore, we evaluated whether PPC consultation is associated with differences in end-of-life (EOL) care patterns for children who underwent SCT and did not survive. Medical records of children who underwent SCT at Boston Children's Hospital/Dana-Farber Cancer Institute for any indication from September 2004 to December 2012 and did not survive were reviewed. Child demographic and clinical characteristics and PPC consultation and EOL care patterns were abstracted. Children who received PPC (PPC group) were compared with those who did not (non-PPC group). Children who received PPC consultation (n = 37) did not differ from the non-PPC group (n = 110) with respect to demographic or clinical characteristics, except they were more likely to have undergone unrelated allogeneic SCT (PPC, 68%; non-PPC, 39%; P = .02) or to have died from treatment-related toxicity (PPC, 76%; non-PPC, 54%; P = .03). PPC consultation occurred at a median of .7 months (interquartile range [IQR], .4 to 4.2) before death. PPC consultations most commonly addressed goals of care/decision-making (92%), psychosocial support (84%), pain management (65%), and non-pain symptom management (70%). Prognosis discussions (ie, the likelihood of survival) occurred more commonly in the PPC group (PPC, 97%; non-PPC, 83%; P = .04), as did resuscitation status discussions (PPC, 88%; non-PPC, 58%; P = .002). These discussions also occurred earlier in the PPC group, for prognosis a median of 8 days (IQR, 4 to 26) before death compared with 2 days (IQR, 1 to 13) in the non PPC group and for resuscitation status a median of 7 days (IQR, 3 to 18) compared with 2 days (IQR, 1 to 5) in the non-PPC group (P < .001 for both of the timing of prognosis and resuscitation status discussions). The PPC group was also was more likely to have resuscitation status documented (PPC, 97%; non-PPC, 68%; P = .002). With respect to patterns of care, compared with non-PPC, the PPC group was as likely to die in a medicalized setting (ie, the hospital) (PPC, 84%; non-PPC, 77%; P = .06) or have hospice care (PPC, 22%; non-PPC, 18%; P = .6). However, among children who died in the hospital, those who received PPC were more likely to die outside the intensive care unit (PPC, 80%; non-PPC, 58%; P = .03). In addition, the PPC group was less likely to receive intervention-focused care such as intubation in the 24 hours before death (PPC, 42%; non-PPC, 66%; P = .02) or cardiopulmonary resuscitation (PPC, 3%; non-PPC, 20%; P = .03) at EOL. Children who received PPC for at least a month were more likely to receive hospice care (PPC, 41%; non-PPC, 5%; P = .01). Children who underwent SCT and did not survive were likely to die in a medicalized setting, irrespective of PPC. However, PPC was associated with less intervention-focused care and greater opportunity for EOL communication and advance preparation. In the intense, cure-oriented SCT setting, PPC may facilitate advance care planning in this high-risk population. PMID- 26903382 TI - Excitation of dark multipolar plasmonic resonances at terahertz frequencies. AB - We experimentally observe the excitation of dark multipolar spoof localized surface plasmon resonances in a hybrid structure consisting of a corrugated metallic disk coupled with a C-shaped dipole resonator. The uncoupled corrugated metallic disk only supports a dipolar resonance in the transmission spectrum due to perfect symmetry of the structure. However, the dark multipolar spoof localized surface plasmon resonances emerge when coupled with a bright C-shaped resonator which is placed in the vicinity of the corrugated metallic disk. These excited multipolar resonances show minimum influence on the coupling distance between the C-shaped resonator and corrugated metallic disk. The resonance frequencies of the radiative modes are controlled by varying the angle of the C shaped resonator and the inner disk radius, both of which play dominant roles in the excitation of the spoof localized surface plasmons. Observation of such a transition from the dark to radiative nature of multipolar spoof localized plasmon resonances would find potential applications in terahertz based resonant plasmonic and metamaterial devices. PMID- 26903383 TI - Optical Coherence Tomography-Based Quantification of Photoreceptor Injury and Recovery in Vogt-Koyanagi-Harada Uveitis. AB - PURPOSE: To determine if the inflammatory composition of subretinal fluid in Vogt Koyanagi-Harada (VKH) serous retinal detachments is predictive of photoreceptor injury, and to quantify photoreceptor recovery, following resolution of these detachments. METHODS: Optical density (OD) measurements of spectral-domain optical coherence tomography (SD-OCT) scans were used to derive the fibrinous index, a measure of the inflammatory composition of subretinal fluid. In order to assess photoreceptor status, photoreceptor outer segment (PROS) volume was measured from SD-OCT scans. RESULTS: The fibrinous index of subretinal fluid in VKH uveitis was strongly correlated with the PROS volume following resolution of subretinal fluid (r = -0.70, p = 0.006). Following fluid resolution, both PROS volume (p < 0.0001) and visual acuity (p = 0.0015) improved. CONCLUSIONS: The fibrinous index of subretinal fluid during the acute stage of VKH can predict photoreceptor status following resolution of subretinal fluid. PROS volume is a useful measure of photoreceptor recovery in VKH. PMID- 26903385 TI - Proximal tibiofibular joint dislocation associated with tibial shaft fractures - 7 Cases. AB - OBJECTIVE: Lower leg fractures of the tibia with or without fracture of the fibula are very common. Proximal tibiofibular joint (PTFJ) dislocation is a very rare injury that can occur together with a tibia shaft fracture. As there is only scarce literature about this injury available, we would like to present our experience with the treatment of this entity. METHODS: We present a small case series of seven patients. In most cases, the tibia fracture was nailed in a closed technique. After distal locking the proximal fibula was exposed by a lateral approach exposing and preserving the peroneal nerve. After anatomical reduction into the corresponding articular facet of the proximal tibia, the fibula was transfixed to the tibia with a positioning screw. This indirectly provided a correct length and rotation of the tibia, which could finally be locked to the nail by inserting the proximal locking bolts. The positioning screw was removed after six weeks prior to full loading. Six of seven patients had been followed up by at least 7 months post-treatment. RESULTS: Out of 663 prospectively collected tibia shaft fractures treated at our institution from 1/2001 to 7/2014, we found seven patients with associated PTFJ dislocation. All except one had been caused by a high energy trauma. After one year, five patients showed excellent results with full range of motion and returning to their sporting activities as before the accident. Two patients have impaired function due to associated injuries. None complained of persistent pain or instability of the PTFJ. CONCLUSION: PTFJ dislocation with tibia shaft fracture can easily be overlooked if one is not familiar with this injury. It is important to diagnose and treat this uncommon dislocation anatomically to achieve good results. Otherwise, as the literature shows, it can lead to chronic instability of the proximal fibula with snapping, proximal fibular pain and even peroneal nerve palsy. Furthermore in complex tibial fractures correct length and rotation only can be restored after referencing with the fibula. We recommend a high index of suspicion of this injury with high energy tibia shaft fractures especially in cases with intact fibula. PMID- 26903384 TI - Oxytocin receptor gene polymorphism modulates the effects of social support on heart rate variability. AB - A large body of empirical research has demonstrated stress-buffering effects of social support. However, recent studies suggest that genetic variation of the oxytocin system (specifically, a common single nucleotide polymorphism, rs53576, of the oxytocin receptor gene) modulates the efficacy of social support. The timing and neurobiological basis of this genetic modulation were investigated using a standardized, laboratory-based psychological stress procedure (Trier Social Stress Test for Groups, TSST-G). To index potential stress buffering effects of social support mediated by the oxytocin system, heart rate variability (HRV) was obtained before and during the TSST-G from 40 healthy participants. Results indicate that social support is associated with higher HRV only in G allele carriers. Specifically, social support increased heart rate variability during direct social interaction and only in individuals with at least one copy of the G allele of rs53576. These findings support the idea that the stress attenuating effects of social support are modulated by genetic variation of the oxytocin system. PMID- 26903386 TI - Hake fish bone as a calcium source for efficient bone mineralization. AB - Calcium is recognized as an essential nutritional factor for bone health. An adequate intake is important to achieve or maintain optimal bone mass in particular during growth and old age. The aim of the present study was to evaluate the efficiency of hake fish bone (HBF) as a calcium source for bone mineralization: in vitro on osteosarcoma SaOS-2 cells, cultured in Ca-free osteogenic medium (OM) and in vivo on young growing rats fed a low-calcium diet. Lithotame (L), a Ca supplement derived from Lithothamnium calcareum, was used as control. In vitro experiments showed that HBF supplementation provided bone mineralization similar to standard OM, whereas L supplementation showed lower activity. In vivo low-Ca HBF-added and L-added diet similarly affected bone deposition. Physico-chemical parameters concerning bone mineralization, such as femur breaking force, tibia density and calcium/phosphorus mineral content, had beneficial effects from both Ca supplementations, in the absence of any evident adverse effect. We conclude HBF derived from by-product from the fish industry is a good calcium supplier with comparable efficacy to L. PMID- 26903387 TI - Harnessing the secretome of cardiac stem cells as therapy for ischemic heart disease. AB - Adult stem cells continue to promise opportunities to repair damaged cardiac tissue. However, precisely how adult stem cells accomplish cardiac repair, especially after ischemic damage, remains controversial. It has been postulated that the clinical benefit of adult stem cells for cardiovascular disease results from the release of cytokines and growth factors by the transplanted cells. Studies in animal models of myocardial infarction have reported that such paracrine factors released from transplanted adult stem cells contribute to improved cardiac function by several processes. These include promoting neovascularization of damaged tissue, reducing inflammation, reducing fibrosis and scar formation, as well as protecting cardiomyocytes from apoptosis. In addition, these factors might also stimulate endogenous repair by activating cardiac stem cells. Interestingly, stem cells discovered to be resident in the heart appear to be functionally superior to extra-cardiac adult stem cells when transplanted for cardiac repair and regeneration. In this review, we discuss the therapeutic potential of cardiac stem cells and how the proteins secreted from these cells might be harnessed to promote repair and regeneration of damaged cardiac tissue. We also highlight how recent controversies about the efficacy of adult stem cells in clinical trials of ischemic heart disease have not dampened enthusiasm for the application of cardiac stem cells and their paracrine factors for cardiac repair: the latter have proved superior to the mesenchymal stem cells used in most clinical trials in the past, some of which appear to have been conducted with sub-optimal rigor. PMID- 26903388 TI - The C421A (Q141K) polymorphism enhances the 3'-untranslated region (3'-UTR) dependent regulation of ATP-binding cassette transporter ABCG2. AB - The impact of the gout-causing C421A (Q141K) single nucleotide polymorphism (SNP) on ABC transporter ABCG2 expression and function has been extensively characterized. However, the influence of the C421A SNP on 3'-UTR-dependent ABCG2 regulation has not been analysed so far. To elucidate this matter, we generated vectors for expression of either the ABCG2 coding sequence (ORF) or the ABCG2 ORF fused to its 3'-UTR, inserted the C421A mutation via site-directed mutagenesis and expressed wild-type and C421A-mutated ABCG2 transcripts in HEK293-Tet-On cells. As shown previously, the C421A SNP significantly reduced ABCG2 protein levels in ABCG2 ORF-transfected HEK293-Tet-On cells. Interestingly, the presence of the 3'-UTR in the ABCG2 transcript dramatically reduced ABCG2 protein content in cells transfected with the C421A variant but not significantly in those transfected with ABCG2 wild-type sequence, whereas ABCG2 mRNA levels were similar. siRNA-mediated DICER1 knockdown to reduce cellular microRNA biogenesis and selective mutation of putative microRNA binding sites within the ABCG2 3'-UTR partially antagonized C421A-associated reduction of ABCG2 protein content but did not significantly affect wild-type ABCG2 protein levels. In addition, antagomir mediated inhibition of two microRNAs (hsa-miR-519c and hsa-miR-328) again partially reversed C421A-associated ABCG2 translational repression, thereby indicating that the C421A SNP may facilitate microRNA-dependent repression of ABCG2 protein translation. We conclude from our results that the C421A SNP may lead to reduced ABCG2 protein levels not only by affecting cellular protein stability but also via enhanced microRNA-dependent ABCG2 repression. Moreover, tissue-specific variation in ABCG2 3'-UTR processing may profoundly affect ABCG2 expression levels in individuals carrying the C421A mutation. PMID- 26903389 TI - The Role of APOE in the Occurrence of Frontotemporal Dementia in Amyotrophic Lateral Sclerosis. AB - IMPORTANCE: Amyotrophic lateral sclerosis (ALS) is a heterogeneous disease with a wide spectrum of involvement of cognitive functions. The mechanisms of this heterogeneity are still largely unknown, but genetic variants may account for this variability. OBJECTIVE: To assess the influence of the apolipoprotein E (APOE) and C9ORF72 genotypes on cognitive impairment in a population-based series of Italian patients with ALS. DESIGN, SETTING, AND PARTICIPANTS: All 504 patients with ALS living in Piemonte, Italy, diagnosed between January 1, 2009, and December 31, 2013, and identified through the Piemonte and Valle d'Aosta register for ALS, were eligible to participate in the study. Controls were 223 age- and sex-matched individuals identified through the patients' general practitioners. Data analysis was performed from June 1 to December 31, 2014. MAIN OUTCOMES AND MEASURES: The presence of APOE and C9ORF72 genotypes was assessed. Patients were cognitively classified as having ALS with normal cognition, ALS with frontotemporal dementia (FTD), ALS with executive or nonexecutive impairment, and ALS with behavioral impairment. RESULTS: Of the 504 patients with incident ALS, 357 (70.8%) were included in the study; 154 were women, 203 were men, they had a mean (SD) age at onset of 64.8 (10.2) years, and 37 of them carried a C9ORF72 repeat expansion. Cognitive testing revealed that 184 patients (51.5%) had ALS with normal cognition, 51 (14.3%) had ALS with FTD, 103 (28.9%) had ALS with executive or nonexecutive impairment, and 19 (5.3%) had ALS with behavioral impairment. Distribution of APOE haplotypes did not significantly differ between patients and controls or among patients with different levels of cognitive impairment. According to multivariate logistic regression, the presence of C9ORF72 repeat expansions was the strongest determinant of FTD (odds ratio, 13.08; 95% CI, 4.75-36.02; P < .001); however, the presence of an APOE epsilon2 allele significantly increased the risk of FTD (odds ratio, 2.61; 95% CI, 1.14 6.10; P = .03). Presence of an APOE epsilon4 allele was ineffectual. CONCLUSIONS AND RELEVANCE: C9ORF72 repeat expansions have a primary role in increasing the risk of cognitive impairment in patients with ALS; the APOE epsilon2 allele, to a lesser extent, also increases the risk of FTD. These study findings highlight the importance of considering the genetic background of patients with ALS when analyzing the putative effect of genetic modifiers. PMID- 26903390 TI - Oral Prednisolone in the Treatment of Acute Gout: A Pragmatic, Multicenter, Double-Blind, Randomized Trial. AB - BACKGROUND: Two recent double-blind, randomized, controlled trials (RCTs) showed that oral steroids and nonsteroidal anti-inflammatory drugs have similar analgesic effectiveness for management of gout, but the trials had small sample sizes and other methodological limitations. OBJECTIVE: To compare the effectiveness and safety of oral prednisolone versus oral indomethacin in patients presenting to emergency departments (EDs) with acute gout. DESIGN: Multicenter, double-blind, randomized equivalence trial. Patients were randomly assigned (1:1 ratio) to receive either indomethacin or prednisolone. (ISRCTN registry number: ISRCTN45724113). SETTING: Four EDs in Hong Kong. PARTICIPANTS: 416 patients aged 18 years or older. MEASUREMENTS: Analgesic effectiveness was defined as changes in pain (at rest or with activity) greater than 13 mm on a 100 mm visual analogue scale. Outcomes were measured during the first 2 hours in the ED and from days 1 to 14. RESULTS: 376 patients completed the study. Equivalent and clinically significant within-group reductions in mean pain score were observed with indomethacin and prednisolone in the ED (approximately 10 mm [rest] and 20 mm [activity]) and from days 1 to 14 (approximately 25 mm [rest] and 45 mm [activity]). No major adverse events occurred during the study. During the ED phase, patients in the indomethacin group had more minor adverse events than those in the prednisolone group (19% vs. 6%; P < 0.001). During days 1 to 14, 37% of patients in each group had minor adverse events. LIMITATION: Diagnosis of gout was usually based on clinical criteria rather than examination of joint fluid. CONCLUSION: Oral prednisolone and indomethacin had similar analgesic effectiveness among patients with acute gout. Prednisolone is a safe, effective first-line option for treatment of acute gout. PRIMARY FUNDING SOURCE: Health and Health Services Research Grant Committee of the Hong Kong Government. PMID- 26903391 TI - Do prevalence expectations affect patterns of visual search and decision-making in interpreting CT colonography endoluminal videos? AB - OBJECTIVE: To assess the effect of expected abnormality prevalence on visual search and decision-making in CT colonography (CTC). METHODS: 13 radiologists interpreted endoluminal CTC fly-throughs of the same group of 10 patient cases, 3 times each. Abnormality prevalence was fixed (50%), but readers were told, before viewing each group, that prevalence was either 20%, 50% or 80% in the population from which cases were drawn. Infrared visual search recording was used. Readers indicated seeing a polyp by clicking a mouse. Multilevel modelling quantified the effect of expected prevalence on outcomes. RESULTS: Differences between expected prevalence were not statistically significant for time to first pursuit of the polyp (median 0.5 s, each prevalence), pursuit rate when no polyp was on screen (median 2.7 s(-1), each prevalence) or number of mouse clicks [mean 0.75/video (20% prevalence), 0.93 (50%), 0.97 (80%)]. There was weak evidence of increased tendency to look outside the central screen area at 80% prevalence and reduction in positive polyp identifications at 20% prevalence. CONCLUSION: This study did not find a large effect of prevalence information on most visual search metrics or polyp identification in CTC. Further research is required to quantify effects at lower prevalence and in relation to secondary outcome measures. ADVANCES IN KNOWLEDGE: Prevalence effects in evaluating CTC have not previously been assessed. In this study, providing expected prevalence information did not have a large effect on diagnostic decisions or patterns of visual search. PMID- 26903393 TI - Cerebral Amyloid Angiopathy-related Intracerebral Hemorrhage Score For Predicting Outcome. AB - The existing intracerebral hemorrhage (ICH) scores were based on the clinical and anatomical parameters of all primary ICH. We aimed to study whether the original ICH Score can predict cerebral amyloid angiopathy (CAA)-related ICH mortality and functional outcome and whether modified score can improve the predictions. The patients with ICH were consecutively recruited from 21 tertiary and secondary hospitals across Mainland China from January 2012 to December 2014. CAA-related ICH was defined as Boston Criteria. Logistic regression was performed in the derivation cohort of patients with CAA-related ICH to identify predictors of 3 month mortality and good outcome [modified Rankin score (mRS) of 0-2 at 3 months]. The areas under the receiver operating characteristic curves (AUCs) were used to assess model discrimination. A total of 360 CAA-related ICH patients were included. According to AUCs, the original ICH Score was less reliable predictor for mortality (AUCs=0.69) and good outcome (AUCs=0.67) in CAA- related patients. The range of CAA-related ICH score values is 0 to 7. The scale consist of four clinical items and the score points were assigned based on the Glasgow Coma Scale score on admission, age, presence of intraventricular hemorrhage, and presence of midline shift. CAA-related ICH score showed good discrimination in the derivation cohort (AUCs: 0.87 for mortality; 0.80 for good clinical outcome) and validation cohort (AUCs: 0.89 for mortality; 0.81 for good clinical outcome). The original ICH Score may be less reliable in predicting mortality and good clinical outcome at 3 months for CAA-related ICH patients. The modified scores improve its ability to predict clinical outcome at 3 months for CAA-related ICH. PMID- 26903392 TI - Alpha/beta (alpha/beta) ratio for prostate cancer derived from external beam radiotherapy and brachytherapy boost. AB - OBJECTIVE: There is disagreement regarding the value of the alpha/beta ratio for prostate cancer. Androgen deprivation therapy (ADT) may dominate the effects of dose fractionation on prostate-specific antigen (PSA) response and confound estimates of the alpha/beta ratio. We estimate this ratio from combined data on external beam radiation therapy (EBRT) and brachytherapy (BT)-treated patients, providing a range of doses per fraction, while accounting for the effects of ADT. METHODS: We analyse data on 289 patients with local prostate cancer treated with EBRT (2 Gy per fraction) or EBRT plus one or two BT boosts of 10 Gy each. The timing of ADT was heterogeneous. We develop statistical models to estimate the alpha/beta ratio based upon PSA measurements at 1 year as a surrogate for the surviving fraction of cancer cells as well as combined biochemical + clinical recurrence-free survival (bcRFS), controlling for ADT. RESULTS: For the PSA-based end point, the alpha/beta ratio estimate is 7.7 Gy [95% confidence interval (CI): 4.1 to 12.5]. Based on the bcRFS end point, the estimate is 18.0 Gy (95% CI: 8.2 to infinity). CONCLUSION: Our model-based estimates of the alpha/beta ratio, which account for the effects of ADT and other important confounders, are higher than some previous estimates. ADVANCES IN KNOWLEDGE: Although dose inhomogeneities and other limitations may limit the scope of our findings, the data suggest caution regarding the assumptions of the alpha/beta ratio for prostate cancer in some clinical environments. PMID- 26903394 TI - Modeling Loss of Microvascular Wall Homeostasis during Glycocalyx Deterioration and Hypertension that Impacts Plasma Filtration and Solute Exchange. AB - The fiber matrix of the surface glycocalyx layer internally coating the endothelial cells and plugging the intercellular clefts is crucial for microvascular wall homeostasis. Disruption of the glycocalyx is found in clinical conditions characterized by microvascular and endothelial dysfunction such as atherosclerosis, diabetes mellitus, chronic renal failure and cerebrovascular disease. Shedding of its components may also occur during oxidative stress and systemic inflammatory states including septis. In this work, we investigate the effects of glycocalyx degradation, either due to enzymatic digestion or to agonist recruitment, on plasma filtration and solute extravasation. We also take into account the possibility of a physiological or pathological increase in blood pressure, as in hypertensive zones such as pre- and post-stenotic blood vessels. Our mathematical model shows that a seriously damaged glycocalyx produces an augmentation of flux of both solvent and solute, thus losing its role of transport barrier and macro-molecular sieve, in agreement with experimental evidence. Similarly, hypertension causes an increase in both volume and solute fluxes, also according to physiological findings. The combination of glycocalyx deterioration and hypertension further raises plasma and solute fluxes, potentially leading in most severe cases to edema and hemorrhage, as in the case of diabetes. PMID- 26903395 TI - International Women's Day. PMID- 26903396 TI - The association between recent incarceration and inpatient resource use and death rates: evaluation of a US veteran sample. PMID- 26903397 TI - Well-defined silica-supported zirconium-imido complexes mediated heterogeneous imine metathesis. AB - Upon prolonged thermal exposure under vacuum, a well-defined single-site surface species [([triple bond, length as m-dash]Si-O-)Zr(NEt2)3] () evolves into an ethylimido complex [([triple bond, length as m-dash]Si-O-)Zr([double bond, length as m-dash]NEt)NEt2] (). Reactions of with an imine substrate result in imido/imine ([double bond, length as m-dash]NRi, R: Et, Ph) exchange (metathesis) with the formation of [([triple bond, length as m-dash]Si-O-)Zr([double bond, length as m-dash]NPh)NEt2] (). Compounds and effectively catalyze imine/imine cross-metathesis and are thus considered as the first heterogeneous catalysts active for imine metathesis. PMID- 26903398 TI - Endothelial and Metabolic Function Interactions in Overweight/Obese Children. AB - AIM: Although the underlined mechanisms are still unknown, metabolic/coagulation alterations related to childhood obesity can induce vascular impairments. The aim of this study was to investigate the relationship between metabolic/coagulation parameters and endothelial function/vascular morphology in overweight/obese children. METHODS: Thirty-five obese/overweight children (22 pre-pubertal, mean age: 9.52+/-3.35 years) were enrolled. Body mass index (BMI), homeostasis model assessment index (HOMAIR), metabolic and coagulation parameters, [adiponectin, fibrinogen, high molecular weight adiponectin (HMW), endothelin-1, and vonWillebrand factor antigen] ultrasound early markers of atherosclerosis [flow mediated dilatation (FMD), common carotid intima-media thickness (C-IMT), and anteroposterior diameter of infra-renal abdominal aorta (APAO)] were assessed. RESULTS: APAO was related to anthropometric (age: r=0.520, p=0.001; height: r=0.679, p<0.001; weight: r=0.548, p=0.001; BMI: r=0.607, p<0.001; SBP: r=0.377, p=0.026) and metabolic (HOMAIR: r=0.357, p=0.035; HMW: r=-0.355, p=0.036) parameters. Age, height, and systolic blood pressure were positively related to increased C-IMT (r=0.352, p=0.038; r=0.356, p=0.036; r=0.346, p=0.042, respectively). FMD was not related to any clinical and biochemical characteristics of the pediatric population. Age, HOMAIR, fasting glucose levels, and HMW were independent predictors for APAO increase. Each unit decrease in HMW concentrations (1 MUg/ml) induced a 0.065 mm increase in APAO. CONCLUSION: High molecular weight adiponectin is related to cardiovascular risk in overweight/obese children. PMID- 26903399 TI - Hepatic Effects of Estrogen on Plasma Distribution of Small Dense Low-Density Lipoprotein and Free Radical Production in Postmenopausal Women. AB - AIM: Hepatic effects of estrogen therapy on low-density lipoprotein (LDL) subfraction or oxidative stress have not been previously evaluated. The purpose of the present study was to investigate whether the differential hepatic effects of estrogen affect plasma distribution of small dense LDL and free radical production in postmenopausal women. METHODS: In all, 45 postmenopausal women were given 0.625 mg/day of oral conjugated equine estrogen (CEE) (n=15), 1.0 mg/day of oral 17beta estradiol (E2) (n=15), or 50 MUg/day of transdermal 17betaE2 (n=15) for 3 months. Subjects received either estrogen alone or with dydrogesterone at 5 mg/day. Plasma concentrations of sex hormone-binding globulin (SHBG), lipids, metallic ions, and derivatives of reactive oxygen metabolites (d-ROMs) were measured. RESULTS: CEE, but not oral 17betaE2, increased the plasma concentrations of triglyceride, copper (Cu), and d-ROMs and the ratio of small dense LDL/total LDL cholesterol, a marker for plasma distribution of small dense LDL. Transdermal 17betaE2 decreased d-ROMs concentrations but did not significantly change other parameters. Plasma concentrations of SHBG increased in the 3 groups. Estrogen-induced changes in triglyceride correlated positively either with changes in SHBG (R=0.52, P=0.0002) or the ratio of small dense LDL/total LDL cholesterol (R=0.65, P<0.0001). Changes in Cu also correlated positively either with changes in SHBG (R=0.85, P<0.0001) or d-ROMs (R=0.86, P<0.0001). CONCLUSION: The hepatic effects of different routes or types of estrogen therapy may be associated with plasma distribution of small dense LDL and free radical production in postmenopausal women. PMID- 26903400 TI - Mutual association of Broad bean wilt virus 2 VP37-derived tubules and plasmodesmata obtained from cytological observation. AB - The movement protein VP37 of broad bean wilt virus 2 (BBWV 2) forms tubules in the plasmodesmata (PD) for the transport of virions between cells. This paper reports a mutual association between the BBWV 2 VP37-tubule complex and PD at the cytological level as determined by transmission electron microscopy. The generation of VP37-tubules within different PD leads to a different occurrence frequency as well as different morphology lines of virus-like particles. In addition, the frequency of VP37-tubules was different between PD found at different cellular interfaces, as well as between single-lined PD and branched PD. VP37-tubule generation also induced structural alterations of PD as well as modifications to the cell wall (CW) in the vicinity of the PD. A structural comparison using three-dimensional (3D) electron tomography (ET), determined that desmotubule structures found in the center of normal PD were absent in PD containing VP37-tubules. Using gold labeling, modification of the CW by callose deposition and cellulose reduction was observable on PD containing VP37-tubule. These cytological observations provide evidence of a mutual association of MP derived tubules and PD in a natural host, improving our fundamental understanding of interactions between viral MP and PD that result in intercellular movement of virus particles. PMID- 26903401 TI - State of science: occupational slips, trips and falls on the same level. AB - Occupational slips, trips and falls on the same level (STFL) result in substantial injuries worldwide. This paper summarises the state of science regarding STFL, outlining relevant aspects of epidemiology, biomechanics, psychophysics, tribology, organisational influences and injury prevention. This review reaffirms that STFL remain a major cause of workplace injury and STFL prevention is a complex problem, requiring multi-disciplinary, multi-faceted approaches. Despite progress in recent decades in understanding the mechanisms involved in STFL, especially slipping, research leading to evidence-based prevention practices remains insufficient, given the problem scale. It is concluded that there is a pressing need to develop better fall prevention strategies using systems approaches conceptualising and addressing the factors involved in STFL, with considerations of the full range of factors and their interactions. There is also an urgent need for field trials of various fall prevention strategies to assess the effectiveness of different intervention components and their interactions. Practitioner Summary: Work-related slipping, tripping and falls on the same level are a major source of occupational injury. The causes are broadly understood, although more attention is needed from a systems perspective. Research has shown preventative action to be effective, but further studies are required to understand which aspects are most beneficial. PMID- 26903402 TI - Common Measures for National Institute of Mental Health Funded Research. PMID- 26903403 TI - Changes in Cannabis Potency Over the Last 2 Decades (1995-2014): Analysis of Current Data in the United States. AB - BACKGROUND: Marijuana is the most widely used illicit drug in the United States and all over the world. Reports indicate that the potency of cannabis preparation has been increasing. This report examines the concentration of cannabinoids in illicit cannabis products seized by the U.S. Drug Enforcement Administration over the last 2 decades, with particular emphasis on Delta(9)-tetrahydrocannabinol and cannabidiol. METHODS: Samples in this report were received over time from materials confiscated by the Drug Enforcement Administration and processed for analysis using a validated gas chromatography with flame ionization detector method. RESULTS: Between January 1, 1995, and December 31, 2014, 38,681 samples of cannabis preparations were received and analyzed. The data showed that although the number of marijuana samples seized over the last 4 years has declined, the number of sinsemilla samples has increased. Overall, the potency of illicit cannabis plant material has consistently increased over time since 1995 from ~4% in 1995 to ~12% in 2014. The cannabidiol content has decreased on average from ~.28% in 2001 to <.15% in 2014, resulting in a change in the ratio of Delta(9)-tetrahydrocannabinol to cannabidiol from 14 times in 1995 to ~80 times in 2014. CONCLUSIONS: There is a shift in the production of illicit cannabis plant material from regular marijuana to sinsemilla. This increase in potency poses higher risk of cannabis use, particularly among adolescents. PMID- 26903404 TI - Regulation of FGF signaling: Recent insights from studying positive and negative modulators. AB - Fibroblast growth factor (FGF) signaling is involved in a multitude of biological processes, while impairment of FGF signaling is implicated in a variety of human diseases including developmental disorders and cancer. Therefore, it is not surprising that FGF activity is regulated at multiple and distinct levels. This review focuses on positive and negative modulation of the FGF signal exemplified by recently identified protein modulators anosmin-1, fibronectin-leucine-rich transmembrane protein 3 (FLRT3) and similar expression to FGF (Sef). We examine how these proteins regulate FGF signaling at multiple levels and across species. Finally, we describe the role of these regulators in human disease. PMID- 26903405 TI - How can macromolecular crowding inhibit biological reactions? The enhanced formation of DNA nanoparticles. AB - In contrast to the already known effect that macromolecular crowding usually promotes biological reactions, solutions of PEG 6k at high concentrations stop the cleavage of DNA by HindIII enzyme, due to the formation of DNA nanoparticles. We characterized the DNA nanoparticles and probed the prerequisites for their formation using multiple techniques such as fluorescence correlation spectroscopy, dynamic light scattering, fluorescence analytical ultracentrifugation etc. In >25% PEG 6k solution, macromolecular crowding promotes the formation of DNA nanoparticles with dimensions of several hundreds of nanometers. The formation of DNA nanoparticles is a fast and reversible process. Both plasmid DNA (2686 bp) and double-stranded/single-stranded DNA fragment (66 bp/nt) can form nanoparticles. We attribute the enhanced nanoparticle formation to the depletion effect of macromolecular crowding. This study presents our idea to enhance the formation of DNA nanoparticles by macromolecular crowding, providing the first step towards a final solution to efficient gene therapy. PMID- 26903406 TI - A Comparison of LC-MS/MS and a Fully Integrated Autosampler/Solid-Phase Extraction System for the Analysis of Protein Binding Samples. AB - A new analysis approach was evaluated for measuring plasma protein binding (PPB) of small molecules using the Agilent RapidFire high-throughput system coupled with a Sciex API 4000 mass spectrometer (RF-MS/MS). Thirty-three proprietary and 12 literature compounds were subjected to rapid equilibrium dialysis (RED) and evaluated in parallel using RF-MS/MS at 16.4 s/sample and traditional liquid chromatography-tandem mass spectrometry (LC-MS/MS) at 3.5 min/sample, thus making the RF-MS/MS analysis over 12 times faster than LC-MS/MS. The high-throughput analysis method that was developed demonstrated excellent correlation with the traditional LC-MS/MS analysis method with an r(2) value of 0.96. The RF-MS/MS analysis method was implemented to increase sample throughput, decrease turnaround time for PPB data, and decrease time burden on existing LC-MS/MS instruments. PMID- 26903407 TI - Rater experience influences reliability and validity of the Brief International Classification of Functioning, Disability, and Health Core Set for Stroke. AB - OBJECTIVE: To investigate how clinical experience and access to patient information regarding functional capability influence inter-rater reliability and validity of the Brief International Classification of Functioning, Disability, and Health Core Set for Stroke (ICF) assessment. METHODS: Study 1 involved expert (clinical experience > 5 years) and novice (clinical experience < 2 years) rater pairs, each evaluating the same post-stroke patients using the ICF assessment (n = 149). Study 2 involved novice raters separately evaluating a different cohort of post-stroke patients with the ICF assessment (n = 78). The novice raters had prior knowledge of patient functioning through conducting 6 clinical tests. RESULTS: For Study 1, the expert rater-pairs (kappa=0.50-0.85 for categories; intra-class correlation (ICC)=0.76-0.96 for components) had higher reliability coefficients than novice rater-pairs (kappa=0.18-0.69 for categories; ICC=0.63 0.88 for components). For Study 2, the novice raters with prior knowledge of patient's functioning yielded significantly higher ICF component scores than those without prior knowledge. The former raters' component scores were comparable to those of the expert rater-pairs. CONCLUSION: Clinical experience in post-stroke rehabilitation enhances inter-rater reliability of ICF assessment. Know-ledge of patient's functional capability, such as conducting common clinical tests in post-stroke rehabilitation, is useful for improving assessment validity. PMID- 26903408 TI - The effects of water and dairy drinks on dietary patterns in overweight adolescents. AB - The aim was to investigate the effects of increased water or dairy intake on total intake of energy, nutrients, foods and dietary patterns in overweight adolescents in the Milk Components and Metabolic Syndrome (MoMS) study (n=173). Participants were randomly assigned to consume 1l/d of skim milk, whey, casein or water for 12 weeks. A decrease in the dietary pattern called Convenience Food, identified by principal component analysis, was observed during the intervention both in the water and dairy groups. Total energy intake decreased by 990.9 kJ/d (236.8 kcal/d) in the water group but was unchanged in the dairy group during intervention. To conclude, an extra intake of fluid seems to favourably affect the rest of the diet by decreasing the intake of convenience foods, including sugar-sweetened beverages. A low energy drink, such as water, seems advantageous considering the total energy intake in these overweight adolescents. This study is registered at clinicaltrials.gov (NCT00785499). PMID- 26903409 TI - Residual force enhancement during multi-joint leg extensions at joint- angle configurations close to natural human motion. AB - The isometric steady-state forces following lengthening are greater than those produced at the same muscle length and activation level but without prior lengthening. Although residual force enhancement (RFE) has been investigated across a range of conditions, its relevance for daily human movement is still poorly understood. We aimed to study RFE in a setup imitating daily activity, i.e., submaximal activation of the lower extremity's muscles with slightly flexed knee joints comparable to human walking. A motor-driven leg press dynamometer was used for randomly arranged purely isometric and isometric-eccentric-isometric contractions. Thirteen subjects performed multi-joint leg extensions, which were feedback-controlled at 30% of maximum voluntary vastus lateralis activation. Isometric-eccentric-isometric contractions incorporated a stretch from 30 degrees to 50 degrees knee flexion, while isometric contractions were performed at 50 degrees knee flexion. Isometric contractions following stretch and purely isometric reference contractions were performed at 50 degrees knee flexion. Kinematics, forces, and muscular activity were measured using 3D optical motion tracking, force plates, and surface EMG of 9 lower limb muscles of the right leg and joint torques were calculated by inverse dynamics. Variables of standardization (EMG, joint angles) showed no differences between contraction conditions. Eight of 13 subjects showed RFE of up to 24.8+/-32.5% for external forces and joint torques. Because the remaining 5 non-responders failed to produce enhanced forces during the stretch, we believe that RFE is functionally relevant for muscle function comparable to everyday human motion but only if there is enhanced force during stretch that sufficiently triggers mechanisms underlying RFE. PMID- 26903410 TI - Effects of fixation and preservation on tissue elastic properties measured by quantitative optical coherence elastography (OCE). AB - Fixed and preserved tissues have been massively used in the development of biomedical equipment and instrumentation. Not only the tissue morphology, but also its mechanical properties need to be considered in the fixation and preservation procedures since mechanical properties have significant influence on the design and performance of such instruments. Understanding the effects of storage and preservation conditions on the mechanical properties of soft tissue has both clinical and experimental significance. To this end, we aimed to study the effects of tissue preservation (by 10% formalin and Thiel fluids) on the elastic properties of five different kinds of fresh tissues from pig and chicken; specifically fat, liver, muscle, tendon and cartilage. The tissue elasticity was measured intensively and strictly within a controlled timeline of 6 months by quantitative optical coherence elastography (OCE) system. Our findings suggest that the elasticity change of tissues in the formalin solution has an ascending trend, but that of Thiel remains almost constant, providing a more real texture and properties. PMID- 26903411 TI - Methods to study differences in cell mobility during skin wound healing in vitro. AB - Wound healing events which occur in humans are difficult to study in animals due to differences in skin physiology. Furthermore there are increasing restrictions in Europe for using animals for testing the therapeutic properties of new compounds. Therefore, in line with the 3Rs (reduction, refinement and replacement of test animals), a number of human in vitro models of different levels of complexity have been developed to investigate cell mobility during wound healing. Keratinocyte, melanocyte, fibroblast and endothelial cell mobility are described, since these are the residential cells which are responsible for restoring the main structural features of the skin. A monolayer scratch assay is used to study random fibroblast and endothelial cell migration in response to EGF and bFGF respectively and a chemotactic assay is used to study directional fibroblast migration towards CCL5. In order to study endothelial sprouting in response to bFGF or VEGF, which involves continuous degradation and resynthesis of a 3D matrix, a fibrin gel is used. Human physiologically relevant tissue-engineered skin models are used to investigate expansion of the stratified, differentiated epidermis (keratinocytes and melanocytes) over a fibroblast populated dermis and also to study migration and distribution of fibroblasts into the dermis. Together these skin models provide a platform for testing the mode of action of novel compounds for enhanced and scar free wound healing. PMID- 26903412 TI - New mitral annular force transducer optimized to distinguish annular segments and multi-plane forces. AB - Limited knowledge exists about the forces acting on mitral valve annuloplasty repair devices. The aim of this study was to develop a new mitral annular force transducer to measure the forces acting on clinically used mitral valve annuloplasty devices. The design of an X-shaped transducer in the present study was optimized for simultaneous in- and out-of-plane force measurements. Each arm was mounted with strain gauges on four circumferential elements to measure out-of plane forces, and the central parts of the X-arms were mounted with two strain gauges to measure in-plane forces. A dedicated calibration setup was developed to calibrate isolated forces with tension and compression for in- and out-of-plane measurements. With this setup, it was possible with linear equations to isolate and distinguish measured forces between the two planes and minimize transducer arm crosstalk. An in-vitro test was performed to verify the crosstalk elimination method and the assumptions behind it. The force transducer was implanted and evaluated in an 80kg porcine in-vivo model. Following crosstalk elimination, in plane systolic force accumulation was found to be in average 4.0+/-0.1N and the out-of-plane annular segments experienced an average force of 1.4+/-0.4N. Directions of the systolic out-of-plane forces indicated movements towards a saddle shaped annulus, and the transducer was able to measure independent directional forces in individual annular segments. Further measurements with the new transducer coupled with clinical annuloplasty rings will provide a detailed insight into the biomechanical dynamics of these devices. PMID- 26903413 TI - The effect of biomechanical variables on force sensitive resistor error: Implications for calibration and improved accuracy. AB - Force Sensitive Resistors (FSRs) are commercially available thin film polymer sensors commonly employed in a multitude of biomechanical measurement environments. Reasons for such wide spread usage lie in the versatility, small profile, and low cost of these sensors. Yet FSRs have limitations. It is commonly accepted that temperature, curvature and biological tissue compliance may impact sensor conductance and resulting force readings. The effect of these variables and degree to which they interact has yet to be comprehensively investigated and quantified. This work systematically assesses varying levels of temperature, sensor curvature and surface compliance using a full factorial design-of experiments approach. Three models of Interlink FSRs were evaluated. Calibration equations under 12 unique combinations of temperature, curvature and compliance were determined for each sensor. Root mean squared error, mean absolute error, and maximum error were quantified as measures of the impact these thermo/mechanical factors have on sensor performance. It was found that all three variables have the potential to affect FSR calibration curves. The FSR model and corresponding sensor geometry are sensitive to these three mechanical factors at varying levels. Experimental results suggest that reducing sensor error requires calibration of each sensor in an environment as close to its intended use as possible and if multiple FSRs are used in a system, they must be calibrated independently. PMID- 26903414 TI - Astragaloside IV improves the isoproterenol-induced vascular dysfunction via attenuating eNOS uncoupling-mediated oxidative stress and inhibiting ROS-NF kappaB pathways. AB - OBJECTIVE: Oxidative stress and inflammation are regarded as two important triggers of endothelial dysfunction and play pivotal role in progression of vascular damage associated with cardiac hypertrophy. Our previous studies demonstrated that astragaloside IV (AsIV) could protect against cardiac hypertrophy in rats induced by isoproterenol (Iso), but its effects on the aorta are not known. In present study, we aimed to assess the effects of AsIV on Isoinduced vascular dysfunction. METHODS: Sprague-Dawley (SD) rats were treated with Iso (10mg/kg/d) alone or in combination with AsIV (50mg/kg/d). RESULTS: Compared with Isotreated alone, AsIV significantly reduced the ratios of heart weight/body weight and left ventricular weight/body weight. AsIV ameliorated the increased vasoconstriction response to phenylephrine induced by Iso and suppressed superoxide anion generation in rat aorta, increased endothelial nitric oxide synthase (eNOS) dimer/monomer ratio and its critical cofactor tetrahydrobiopterin (BH4) content in aorta as well as the NO production in the serum, reduced the plasmatic peroxynitrite (ONOO-). Moreover, in contrast with Isotreatment alone, AsIV decreased the ratio of nuclear-to-cytosolic protein expression of the NF-kappaB p65 subunit while enhanced its inhibited protein expression of IkappaB-alpha, down-regulated mRNA expression of IL-1beta, IL-6 and TNF-alpha of the aorta. CONCLUSIONS: The present study suggested that AsIV protects against Isoinduced vascular dysfunction probably via attenuating eNOS uncoupling-mediated oxidative stress and inhibiting ROS-NF-kappaB pathways. PMID- 26903415 TI - Two Unrelated 8-Vinyl Reductases Ensure Production of Mature Chlorophylls in Acaryochloris marina. AB - The major photopigment of the cyanobacterium Acaryochloris marina is chlorophyll d, while its direct biosynthetic precursor, chlorophyll a, is also present in the cell. These pigments, along with the majority of chlorophylls utilized by oxygenic phototrophs, carry an ethyl group at the C-8 position of the molecule, having undergone reduction of a vinyl group during biosynthesis. Two unrelated classes of 8-vinyl reductase involved in the biosynthesis of chlorophylls are known to exist, BciA and BciB. The genome of Acaryochloris marina contains open reading frames (ORFs) encoding proteins displaying high sequence similarity to BciA or BciB, although they are annotated as genes involved in transcriptional control (nmrA) and methanogenesis (frhB), respectively. These genes were introduced into an 8-vinyl chlorophyll a-producing DeltabciB strain of Synechocystis sp. strain PCC 6803, and both were shown to restore synthesis of the pigment with an ethyl group at C-8, demonstrating their activities as 8-vinyl reductases. We propose that nmrA and frhB be reassigned as bciA and bciB, respectively; transcript and proteomic analysis of Acaryochloris marina reveal that both bciA and bciB are expressed and their encoded proteins are present in the cell, possibly in order to ensure that all synthesized chlorophyll pigment carries an ethyl group at C-8. Potential reasons for the presence of two 8-vinyl reductases in this strain, which is unique for cyanobacteria, are discussed. IMPORTANCE: The cyanobacterium Acaryochloris marina is the best-studied phototrophic organism that uses chlorophyll d for photosynthesis. Unique among cyanobacteria sequenced to date, its genome contains ORFs encoding two unrelated enzymes that catalyze the reduction of the C-8 vinyl group of a precursor molecule to an ethyl group. Carrying a reduced C-8 group may be of particular importance to organisms containing chlorophyll d Plant genomes also contain orthologs of both of these genes; thus, the bacterial progenitor of the chloroplast may also have contained both bciA and bciB. PMID- 26903416 TI - Protein Network of the Pseudomonas aeruginosa Denitrification Apparatus. AB - Oxidative phosphorylation using multiple-component, membrane-associated protein complexes is the most effective way for a cell to generate energy. Here, we systematically investigated the multiple protein-protein interactions of the denitrification apparatus of the pathogenic bacterium Pseudomonas aeruginosa During denitrification, nitrate (Nar), nitrite (Nir), nitric oxide (Nor), and nitrous oxide (Nos) reductases catalyze the reaction cascade of NO(3-)-> NO(2-)-> NO -> N2O -> N2 Genetic experiments suggested that the nitric oxide reductase NorBC and the regulatory protein NosR are the nucleus of the denitrification protein network. We utilized membrane interactomics in combination with electron microscopy colocalization studies to elucidate the corresponding protein-protein interactions. The integral membrane proteins NorC, NorB, and NosR form the core assembly platform that binds the nitrate reductase NarGHI and the periplasmic nitrite reductase NirS via its maturation factor NirF. The periplasmic nitrous oxide reductase NosZ is linked via NosR. The nitrate transporter NarK2, the nitrate regulatory system NarXL, various nitrite reductase maturation proteins, NirEJMNQ, and the Nos assembly lipoproteins NosFL were also found to be attached. A number of proteins associated with energy generation, including electron donating dehydrogenases, the complete ATP synthase, almost all enzymes of the tricarboxylic acid (TCA) cycle, and the Sec system of protein transport, among many other proteins, were found to interact with the denitrification proteins. This deduced nitrate respirasome is presumably only one part of an extensive cytoplasmic membrane-anchored protein network connecting cytoplasmic, inner membrane, and periplasmic proteins to mediate key activities occurring at the barrier/interface between the cytoplasm and the external environment. IMPORTANCE: The processes of cellular energy generation are catalyzed by large multiprotein enzyme complexes. The molecular basis for the interaction of these complexes is poorly understood. We employed membrane interactomics and electron microscopy to determine the protein-protein interactions involved. The well-investigated enzyme complexes of denitrification of the pathogenic bacterium Pseudomonas aeruginosa served as a model. Denitrification is one essential step of the universal N cycle and provides the bacterium with an effective alternative to oxygen respiration. This process allows the bacterium to form biofilms, which create low-oxygen habitats and which are a key in the infection mechanism. Our results provide new insights into the molecular basis of respiration, as well as opening a new window into the infection strategies of this pathogen. PMID- 26903417 TI - Regulation of Growth, Cell Shape, Cell Division, and Gene Expression by Second Messengers (p)ppGpp and Cyclic Di-GMP in Mycobacterium smegmatis. AB - The alarmone (p)ppGpp regulates transcription, translation, replication, virulence, lipid synthesis, antibiotic sensitivity, biofilm formation, and other functions in bacteria. Signaling nucleotide cyclic di-GMP (c-di-GMP) regulates biofilm formation, motility, virulence, the cell cycle, and other functions. In Mycobacterium smegmatis, both (p)ppGpp and c-di-GMP are synthesized and degraded by bifunctional proteins Rel(Msm) and DcpA, encoded by rel(Msm) and dcpA genes, respectively. We have previously shown that the Deltarel(Msm) and DeltadcpA knockout strains are antibiotic resistant and defective in biofilm formation, show altered cell surface properties, and have reduced levels of glycopeptidolipids and polar lipids in their cell wall (K. R. Gupta, S. Kasetty, and D. Chatterji, Appl Environ Microbiol 81:2571-2578, 2015,http://dx.doi.org/10.1128/AEM.03999-14). In this work, we have explored the phenotypes that are affected by both (p)ppGpp and c-di-GMP in mycobacteria. We have shown that both (p)ppGpp and c-di-GMP are needed to maintain the proper growth rate under stress conditions such as carbon deprivation and cold shock. Scanning electron microscopy showed that low levels of these second messengers result in elongated cells, while high levels reduce the cell length and embed the cells in a biofilm-like matrix. Fluorescence microscopy revealed that the elongated Deltarel(Msm) and DeltadcpA cells are multinucleate, while transmission electron microscopy showed that the elongated cells are multiseptate. Gene expression analysis also showed that genes belonging to functional categories such as virulence, detoxification, lipid metabolism, and cell-wall-related processes were differentially expressed. Our results suggests that both (p)ppGpp and c-di-GMP affect some common phenotypes in M. smegmatis, thus raising a possibility of cross talk between these two second messengers in mycobacteria. IMPORTANCE: Our work has expanded the horizon of (p)ppGpp and c-di-GMP signaling in Gram-positive bacteria. We have come across a novel observation that M. smegmatis needs (p)ppGpp and c-di-GMP for cold tolerance. We had previously shown that the Deltarel(Msm) and DeltadcpA strains are defective in biofilm formation. In this work, the overproduction of (p)ppGpp and c-di-GMP encased M. smegmatis in a biofilm-like matrix, which shows that both (p)ppGpp and c-di-GMP are needed for biofilm formation. The regulation of cell length and cell division by (p)ppGpp was known in mycobacteria, but our work shows that c-di-GMP also affects the cell size and cell division in mycobacteria. This is perhaps the first report of c-di GMP regulating cell division in mycobacteria. PMID- 26903419 TI - Memory for pure tone sequences without contour. AB - We presented pure tones interspersed with white noise sounds to disrupt contour perception in an acoustic short-term memory (ASTM) experiment during which we recorded the electroencephalogram. The memory set consisted of seven stimuli, 0, 1, 2, 3, or 4 of which were to-be-remembered tones. We estimated each participant's capacity, K, for each set size and measured the amplitude of the SAN (sustained anterior negativity, an ERP related to acoustic short-term memory). We correlated their K slopes with their SAN amplitude slopes as a function of set size, and found a significant link between performance and the SAN: a larger increase in SAN amplitude was linked with a larger number of stimuli maintained in ASTM. The SAN decreased in amplitude in the later portion of the silent retention interval, but the correlation between the SAN and capacity remained strong. These results show the SAN is not an index of contour but rather an index of the maintenance of individual objects in STM. This article is part of a Special Issue entitled SI: Auditory working memory. PMID- 26903418 TI - Language-experience plasticity in neural representation of changes in pitch salience. AB - Neural representation of pitch-relevant information at the brainstem and cortical levels of processing is influenced by language experience. A well-known attribute of pitch is its salience. Brainstem frequency following responses and cortical pitch specific responses, recorded concurrently, were elicited by a pitch salience continuum spanning weak to strong pitch of a dynamic, iterated rippled noise pitch contour-homolog of a Mandarin tone. Our aims were to assess how language experience (Chinese, English) affects i) enhancement of neural activity associated with pitch salience at brainstem and cortical levels, ii) the presence of asymmetry in cortical pitch representation, and iii) patterns of relative changes in magnitude along the pitch salience continuum. Peak latency (Fz: Na, Pb, and Nb) was shorter in the Chinese than the English group across the continuum. Peak-to-peak amplitude (Fz: Na-Pb, Pb-Nb) of the Chinese group grew larger with increasing pitch salience, but an experience-dependent advantage was limited to the Na-Pb component. At temporal sites (T7/T8), the larger amplitude of the Chinese group across the continuum was both limited to the Na-Pb component and the right temporal site. At the brainstem level, F0 magnitude gets larger as you increase pitch salience, and it too reveals Chinese superiority. A direct comparison of cortical and brainstem responses for the Chinese group reveals different patterns of relative changes in magnitude along the pitch salience continuum. Such differences may point to a transformation in pitch processing at the cortical level presumably mediated by local sensory and/or extrasensory influence overlaid on the brainstem output. PMID- 26903421 TI - Biodiversity and health: Lessons and recommendations from an interdisciplinary conference to advise Southeast Asian research, society and policy. AB - Southeast Asia is an economic, biodiverse, cultural and disease hotspot. Due to rapid socio-economic and environmental changes, the role of biodiversity and ecosystems for human health ought to be examined and communicated to decision makers and the public. We therefore summarized the lessons and recommendations from an interdisciplinary conference convened in Cambodia in 2014 to advise Southeast Asian societies on current research efforts, future research needs, and to provide suggestions for improved education, training and science-policy interactions. First, we reviewed several examples of the important role of ecosystems as 'sentinels' in the sense that potentially harmful developments for human health become first apparent in ecosystem components. Other ecosystem services which also benefit human well-being are briefly summarized. Second, we summarized the recommendations of the conference's roundtable discussions and added recent developments in the science-policy interface. The recommendations were organized along five themes: Ethical and legal considerations; implementation of the One Health approach; education, training, and capacity building; future research priorities; and potential science-policy interactions. While the role of biodiversity for human health needs further research, especially for zoonoses and emerging diseases, many direct and indirect benefits to human health are already apparent, but have yet to filter down to the science policy interface in order to influence legislation and enforcement. Therefore, efforts to strengthen the interface in Southeast Asia should become a high priority in order to strengthen the health and resilience of Southeast Asian societies. PMID- 26903420 TI - Retrograde optogenetic characterization of the pontospinal module of the locus coeruleus with a canine adenoviral vector. AB - Noradrenergic neurons of the brainstem extend projections throughout the neuraxis to modulate a wide range of processes including attention, arousal, autonomic control and sensory processing. A spinal projection from the locus coeruleus (LC) is thought to regulate nociceptive processing. To characterize and selectively manipulate the pontospinal noradrenergic neurons in rats, we implemented a retrograde targeting strategy using a canine adenoviral vector to express channelrhodopsin2 (CAV2-PRS-ChR2-mCherry). LC microinjection of CAV2-PRS-ChR2 mCherry produced selective, stable, transduction of noradrenergic neurons allowing reliable opto-activation in vitro. The ChR2-transduced LC neurons were opto-identifiable in vivo and functional control was demonstrated for >6 months by evoked sleep-wake transitions. Spinal injection of CAV2-PRS-ChR2-mCherry retrogradely transduced pontine noradrenergic neurons, predominantly in the LC but also in A5 and A7. A pontospinal LC (ps:LC) module was identifiable, with somata located more ventrally within the nucleus and with a discrete subset of projection targets. These ps:LC neurons had distinct electrophysiological properties with shorter action potentials and smaller afterhyperpolarizations compared to neurons located in the core of the LC. In vivo recordings of ps:LC neurons showed a lower spontaneous firing frequency than those in the core and they were all excited by noxious stimuli. Using this CAV2-based approach we have demonstrated the ability to retrogradely target, characterise and optogenetically manipulate a central noradrenergic circuit and show that the ps:LC module forms a discrete unit. This article is part of a Special Issue entitled SI: Noradrenergic System. PMID- 26903422 TI - Proteogenomic Analysis of a Hibernating Mammal Indicates Contribution of Skeletal Muscle Physiology to the Hibernation Phenotype. AB - Mammalian hibernation is a strategy employed by many species to survive fluctuations in resource availability and environmental conditions. Hibernating mammals endure conditions of dramatically depressed heart rate, body temperature, and oxygen consumption yet do not show the typical pathological response. Because of the high abundance and metabolic cost of skeletal muscle, not only must it adjust to the constraints of hibernation, but also it is positioned to play a more active role in the initiation and maintenance of the hibernation phenotype. In this study, MS/MS proteomic data from thirteen-lined ground squirrel skeletal muscles were searched against a custom database of transcriptomic and genomic protein predictions built using the platform Galaxy-P. This proteogenomic approach allows for a thorough investigation of skeletal muscle protein abundance throughout their circannual cycle. Of the 1563 proteins identified by these methods, 232 were differentially expressed. These data support previously reported physiological transitions, while also offering new insight into specific mechanisms of how their muscles might be reducing nitrogenous waste, preserving mass and function, and signaling to other tissues. Additionally, the combination of proteomic and transcriptomic data provides unique opportunities for estimating post-transcriptional regulation in skeletal muscle throughout the year and improving genomic annotation for this nonmodel organism. PMID- 26903423 TI - A Most Interesting and Wonderful Time as an Editor. PMID- 26903424 TI - Penalty for Delay of Game? Sobering Results in Treating Adolescent Depression. PMID- 26903425 TI - If You Do Not Ask, They Will Not Tell: Evaluating Pregnancy Risk in Young Women in Pediatric Hospitals. AB - Adolescents experience some of the highest rates of unintended pregnancy among women of all reproductive age groups. And despite the fact that adolescents often receive care in pediatric hospital settings, evaluation of pregnancy risk is inconsistent. Pregnancy risk assessments can identify opportunities to deliver reproductive health services, allow earlier pregnancy diagnoses, and reduce morbidity and mortality for medically complex adolescent patients and their pregnancies. In this commentary we discuss some of the challenges and potential solutions to performing pregnancy risk assessments in pediatric hospital settings. PMID- 26903426 TI - Transitions in Friendship Attachment During Adolescence are Associated With Developmental Trajectories of Depression Through Adulthood. AB - PURPOSE: Forming secure friendship attachments during adolescence are important for mental health; few, however, have specifically examined the ways in which the transitions in attachment during adolescence may influence future mental health outcomes among African Americans. METHODS: The present study examines how transitions in attachment in adolescence predicted changes in depression symptoms from late adolescents through adulthood in an African-American sample. We used growth curve modeling to examine the association between transitions in friendship attachment and changes in depression symptoms in adulthood. RESULTS: At age 16 years, 346 (64.0%) adolescents reported secure attachment with 195 (36.0%) reporting either avoidant or resistant attachment. At age 17 years, 340 (62.9%) reported secure attachment and 201 (37.2%) reported avoidant or resistant attachment. The largest percentage of participants (46.2%) reported stable-secure attachment across the two time points. Results of the growth model indicated that adolescents who reported a stable-secure attachment style had lower levels of depression symptoms during adulthood than those individuals who transitioned from secure-to-insecure, from insecure-to-secure, or were in the stable-insecure group. Interestingly enough, individuals in both the attachment transition groups had a faster declining rate of depression symptoms over time compared to the two stability groups. CONCLUSIONS: Data support existing research showing an association between transitions in attachment during adolescence and depression through adulthood. Furthermore, these study findings suggest there may be protective features associated with transitioning between attachment styles during adolescence on later depression, compared to African Americans who remain stable in their attachment style. PMID- 26903427 TI - Barriers and Facilitators to Health Center Implementation of Evidence-Based Clinical Practices in Adolescent Reproductive Health Services. AB - PURPOSE: Despite the substantial evidence supporting the guidelines for the provision of reproductive health services for adolescents, research points to a persistent gap in their translation into health care practice. This study examines barriers and facilitators that health centers experience when implementing evidence-based clinical practices for adolescent reproductive health services and discusses strategies to address identified barriers. METHODS: Semistructured interviews were conducted with 85 leaders and staff of 30 health centers in Alabama, Georgia, Massachusetts, North Carolina, South Carolina, Pennsylvania, and Texas. Interview data were analyzed for emergent themes following a grounded theory approach. RESULTS: Data analysis revealed that certain factors at health system and community levels influenced health centers' efforts to implement evidence-based clinical practices for adolescent reproductive health care. In particular, support from health center leadership, communication between leadership and staff, and staff attitudes and beliefs were reported as factors that facilitated the implementation of new practices. CONCLUSIONS: Health center efforts to implement new practice guidelines should include efforts to build the capacity of health center leadership to mobilize staff and resources to ensure that new practices are implemented consistently and with quality. PMID- 26903428 TI - Etonogestrel Implants in Adolescents: Experience, Satisfaction, and Continuation. AB - PURPOSE: Few studies have evaluated the use of etonogestrel subdermal implants (ESI) by U.S. adolescents. We assessed several factors, including continuation rates, the association of implant removal with postimplant management of nuisance bleeding, and the relation between bleeding and body mass index. METHODS: We reviewed 116 charts from all adolescent females with ESI placement in our adolescent medicine clinic from January 2010 to August 2013. Data were obtained from follow-up encounters up to 36 months after insertion. RESULTS: Of the 116 adolescents, 94% were nulliparous. Follow-up data were available for 81% (n = 94). Early ESI removal was defined as removal <32 months. ESI continuation rates at 12, 24, and 32 months were 78%, 50%, and 40%, respectively; this represents an early removal rate of 35% (33 of 94). Nuisance bleeding occurred in 48% (45 of 94). Of those complaining of bleeding, 63% (25 of 40) received medication management. Resolution of bleeding occurred in 25% of those in the early removal group versus 15% in the full retention group. Early implant removal due to nuisance bleeding occurred in 18% (17 of 94). There was no significant association between body mass index, nuisance bleeding, and early ESI removal. CONCLUSIONS: Implant continuation rates were quite high at 12 and 24 months, with 40% of patients reaching 32 months retention, providing a significant period of pregnancy prevention. Treatments for nuisance bleeding were often not prescribed and when they were, medication regimens varied among providers. An evidence-based protocol for medication management, combined with more routine use of appropriate medications and preventive or long-term therapies, may help improve continuation of ESI. PMID- 26903429 TI - Sexual Behaviors and Partner Characteristics by Sexual Identity Among Adolescent Girls. AB - PURPOSE: Data suggest that lesbian and bisexual adolescents engage in risky sexual behaviors at higher rates than heterosexual girls. Whether these findings also apply to girls of other sexual identities is less well understood. Potential differences in risky sexual behaviors reported by lesbian versus bisexual adolescents are also underreported in the literature. METHODS: Data were collected online in 2010-2011 among 2,823 girls, aged 13-18 years, in the United States. Multinomial logistic regression was used to quantify comparisons of sexual behaviors between (1) lesbian; (2) bisexual; and (3) questioning, unsure, or other (QUO) identity; and (0) heterosexual girls. Logistic regression compared lesbian and bisexual adolescents. RESULTS: Lesbian and bisexual adolescents reported significantly more lifetime and past-year sexual partners than heterosexual girls. Bisexual girls were also more likely to report penile-anal and penile-vaginal sex, whereas lesbians were more likely to report earlier sexual debut for almost all types of sex, as compared to heterosexual girls. Lesbians also were more likely to report infrequent condom use and less likely to have conversations with partners about the use of barriers (e.g., dental dams) before first sex. Relative to lesbians, bisexual girls reported older age at first sex for almost all sexual behaviors and higher lifetime prevalence of recent male partners, penile-vaginal, and penile-anal sex. Few differences were noted between QUO and heterosexual girls. CONCLUSIONS: Sexual minority adolescents are not identical in terms of sexual risk. Providers need to be sensitive to these differences and their implications for health and counseling of patients. PMID- 26903430 TI - Rap Music Use, Perceived Peer Behavior, and Sexual Initiation Among Ethnic Minority Youth. AB - PURPOSE: Research shows that rap music use is associated with risky sexual behavior in ethnic minority youth; however, it is unknown whether rap music use impacts sexual initiation specifically and, if so, which factors mediate this impact. Thus, we investigated the longitudinal relationship between hours spent listening to rap music in seventh grade and sexual initiation in ninth grade. We also examined the role of perceived peer sexual behavior as a potential mediator of this relationship. METHODS: We analyzed data from students (n = 443) enrolled in a school-based randomized controlled trial of a sexual health education curriculum collected at baseline and at 18-month follow-up. Rap music use and perceived peer sexual behavior were assessed in seventh grade, whereas sexual initiation was assessed in ninth grade. Univariate, multivariate, and mediation analyses were conducted. RESULTS: At baseline, rap music use was significantly associated with race/ethnicity, parental music rules, and sexual behavior, but not with gender or parental education. Rap music use was a significant predictor of sexual initiation on univariate analysis but not multivariate analysis. Mediation analysis showed that the association between hours spent listening to rap music and sexual initiation was significantly mediated by perceived peer sexual behavior. CONCLUSIONS: Rap music use in early adolescence significantly impacts sexual initiation in late adolescence, partially mediated by perceived peer sexual behavior. More research is needed to understand how rap music influences perceptions of peer sexual behavior, which, in turn, influence early sexual initiation. PMID- 26903431 TI - Bullying Victimization Among School-Aged Immigrant Youth in the United States. AB - PURPOSE: Bullying is a serious sociodevelopmental issue associated with a range of short- and long-term problems among youth who are bullied. Although race and ethnicity have been studied, less attention has been paid to examining prevalence and correlates of bullying victimization among immigrant youth. METHODS: Using data from the Health Behavior in School-Aged Children (N = 12,098), we examined prevalence and correlates of bullying victimization among U.S. immigrant youth. RESULTS: After controlling for several demographic variables, findings indicate that immigrant youth are more likely to experience bullying victimization than native-born youth. Furthermore, immigrant youth who experience bullying victimization were more likely to report interpersonal, socioemotional, health, and substance use problems. CONCLUSIONS: Given the greater risk and unique challenges experienced by immigrant youth, prevention and intervention programs may need to be tailored to their specific needs and circumstances. Further research is needed to understand the specific factors and mechanisms involved in bullying victimization among immigrant youth. PMID- 26903432 TI - Relationships Between Current and Past Binge Drinking and Systolic Blood Pressure in Young Adults. AB - PURPOSE: Heavy episodic (i.e., "binge") drinking (i.e., >=five drinks/occasion) is highly prevalent among young adults; those who binge do so four times per month on average, consuming nine drinks on average on each occasion. Although it is well established that chronic heavy drinking (>=two alcoholic beverages per day) increases the risk of hypertension, the relationship between binge drinking and blood pressure is not well described. Our aim was to describe the relationship between frequency of binge drinking, both current (at age 24 years) and past (at age 20 years), and systolic blood pressure (SBP) at age 24 years. METHODS: Participants (n = 756) from the longitudinal Nicotine Dependence in Teens study reported alcohol consumption at ages 20 and 24 years and had SBP measured at age 24 years. We examined the association between binge drinking and SBP using multiple linear regression, controlling for sex, race/ethnicity, education, monthly drinking in high school, cigarette smoking, and body mass index. RESULTS: Compared to nonbinge drinkers, SBP at age 24 years was 2.61 [.41, 4.82] mm Hg higher among current monthly bingers and 4.03 [1.35, 6.70] mm Hg higher among current weekly bingers. SBP at age 24 years was 2.90 [.54, 5.25] mm Hg higher among monthly bingers at age 20 years and 3.64 [.93, 6.35] mm Hg higher among weekly bingers at age 20 years, compared to nonbinge drinkers. CONCLUSIONS: Frequent binge drinking at ages 20 and 24 years is associated with higher SBP at age 24 years and may be implicated in the development of hypertension. PMID- 26903434 TI - Characteristics of Referrals for Gender Dysphoria Over a 13-Year Period. AB - PURPOSE: Our Pediatric Endocrinology Clinic has seen a sharp increase in referrals for gender dysphoria (GD) during recent years. However, the frequency and characteristics of referrals have not been objectively examined. METHODS: A retrospective chart review of referrals for GD during the past 13 years was performed. Variables analyzed included numbers of referrals per year, patient characteristics, comorbid conditions, and hormonal therapy. Timing of referral and eligibility for treatment were measured against established recommendations. RESULTS: Of 38 patients, 74% were referred during the last 3 years. Most patients presented late in puberty before a GD-specific psychological evaluation and few were eligible for hormonal treatment at baseline. Over half had psychiatric and/or developmental comorbidities. CONCLUSIONS: A dramatic increase in referrals for GD since 2002 was confirmed. Enhanced provider education and outreach regarding care of patients with GD are needed. PMID- 26903433 TI - Prevalence and Correlates of E-Cigarette Perceptions and Trial Among Early Adolescents in Mexico. AB - PURPOSE: Assess the prevalence and correlates of e-cigarette perceptions and trial among adolescents in Mexico, where e-cigarettes are banned. METHODS: Cross sectional data were collected in 2015 from a representative sample of middle school students (n = 10,146). Prevalence of e-cigarette awareness, relative harm, and trial were estimated, adjusting for sampling weights and school-level clustering. Multilevel logistic regression models adjusted for school-level clustering to assess correlates of e-cigarette awareness and trial. Finally, students who had tried only e-cigarettes were compared with students who had tried: (1) conventional cigarettes only; (2) both e-cigarettes and conventional cigarettes (dual triers); and (3) neither cigarette type (never triers). RESULTS: Fifty-one percent of students had heard about e-cigarettes, 19% believed e cigarettes were less harmful than conventional cigarettes, and 10% had tried them. Independent correlates of e-cigarette awareness and trial included established risk factors for smoking, as well as technophilia (i.e., use of more media technologies) and greater Internet tobacco advertising exposure. Exclusive e-cigarette triers (4%) had significantly higher technophilia, bedroom Internet access, and Internet tobacco advertising exposure compared to conventional cigarette triers (19%) and never triers (71%) but not compared to dual triers (6%), although dual triers had significantly stronger conventional cigarette risk factors. CONCLUSIONS: This study suggests that adolescent e-cigarette awareness and use is high in Mexico, in spite of its e-cigarette ban. A significant number of medium-risk youth have tried e-cigarettes only, suggesting that e-cigarettes could lead to more intensive substance use. Strategies to reduce e-cigarette use should consider reducing exposures to Internet marketing. PMID- 26903436 TI - The Author reply. PMID- 26903435 TI - U.S. Cervical Cancer Mortality. PMID- 26903437 TI - Confidentiality Protections for Adolescents and Young Adults in the Health Care Billing and Insurance Claims Process. AB - The importance of protecting confidential health care for adolescents and young adults is well documented. State and federal confidentiality protections exist for both minors and young adults, although the laws vary among states, particularly for minors. However, such confidentiality is potentially violated by billing practices and in the processing of health insurance claims. To address this problem, policies and procedures should be established so that health care billing and insurance claims processes do not impede the ability of providers to deliver essential health care services on a confidential basis to adolescents and young adults covered as dependents on a family's health insurance plan. PMID- 26903439 TI - A non-typical sequence of phase transitions in (NH4)3GeF7: optical and structural characterization. AB - Single crystals of germanium double salt (NH4)3GeF7 = (NH4)2GeF6.NH4F = (NH4)3[GeF6]F were grown and studied by the methods of polarization optics and X ray diffraction. The birefringence Deltan = (no - ne), the rotation angle of the optical indicatrix phi(T) and unit cell parameters were measured in the temperature range 100-400 K. Three structural phase transitions were found at the temperatures: T1? = 279.2 K (T1? = 279.4 K), T2? = 270 K (T2? = 268.9 K), T3? = 218 K (T3? = 227 K). An unusual sequence of symmetry transformations with temperature change was established: P4/mbm (Z = 2) (G1) <-> Pbam (Z = 4) (G2) <-> P21/c (Z = 4) (G3) <-> Pa3[combining macron] (Z = 8) (G4). The crystal structures of different phases were determined. The experimental data were additionally interpreted by a group-theoretical analysis of the complete condensate of order parameters taking into account the critical and noncritical atomic displacements. Strengthening of the N-HF hydrogen bonds can be a driving force of the observed phase transitions. PMID- 26903438 TI - Keratan sulfate glycosaminoglycan from chicken egg white. AB - Keratan sulfate (KS) was isolated from chicken egg white in amounts corresponding to ~0.06 wt% (dry weight). This KS had a weight-average molecular weight of ~36 41 kDa with a polydispersity of ~1.3. The primary repeating unit present in chicken egg white KS was ->4) beta-N-acetyl-6-O-sulfo-d-glucosamine (1 -> 3) beta d-galactose (1-> with some 6-O-sulfo galactose residues present. This KS was somewhat resistant to depolymerization using keratanase 1 but could be depolymerized efficiently through the use of reactive oxygen species generated using copper (II) and hydrogen peroxide. Of particular interest was the presence of substantial amounts of 2,8- and 2,9-linked N-acetylneuraminic acid residues in the form of oligosialic acid terminating the non-reducing ends of the KS chains. Most of the KS appears to be N-linked to a protein core as evidenced by its sensitivity to PNGase F. PMID- 26903440 TI - Pleiotropic roles of metallothioneins as regulators of chondrocyte apoptosis and catabolic and anabolic pathways during osteoarthritis pathogenesis. AB - OBJECTIVE: The zinc-ZIP8-MTF1 axis induces metallothionein (MT) expression and is a catabolic regulator of experimental osteoarthritis (OA) in mice. The main aim of the current study was to explore the roles and underlying molecular mechanisms of MTs in OA pathogenesis. METHODS: Experimental OA in mice was induced by destabilisation of the medial meniscus or intra-articular injection of adenovirus carrying a target gene (Ad-Zip8, Ad-Mtf1, Ad-Epas1, Ad-Nampt, Ad-Mt1 or Ad-Mt2) into wild type, Zip8fl/fl; Col2a1-Cre, Mtf1fl/fl; Col2a1-Cre and Mt1/Mt2 double knockout mice. Primary cultured mouse chondrocytes were infected with Ad-Mt1 or Ad-Mt2, and gene expression profiles analysed via microarray and reverse transcription-PCR. Proteins in human and mouse OA cartilage were identified via immunostaining. Chondrocyte apoptosis in OA cartilage was determined using terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick end labelling (TUNEL). RESULTS: MTs were highly expressed in human and mouse OA cartilage. Hypoxia-inducible factor 2alpha, nicotinamide phosphoribosyltransferase and several proinflammatory cytokine pathways, as well as the zinc-ZIP8-MTF1 axis were identified as upstream regulators of MT expression. Genetic deletion of Mt1 and Mt2 enhanced cartilage destruction through increasing chondrocyte apoptosis. Unexpectedly, aberrant overexpression of MT2, but not MT1, induced upregulation of matrix-degrading enzymes and downregulation of matrix molecules through nuclear factor-kappa B (NF-kappaB) and activator protein-1 (AP-1) activation, ultimately leading to OA. CONCLUSIONS: MTs play an antiapoptotic role in post-traumatic OA. However, aberrant and chronic upregulation of MT2 triggers an imbalance between chondrocyte anabolism and catabolism, consequently accelerating OA development. Our findings collectively highlight pleiotropic roles of MTs as regulators of chondrocyte apoptosis as well as catabolic and anabolic pathways during OA pathogenesis. PMID- 26903441 TI - High sodium chloride consumption enhances the effects of smoking but does not interact with SGK1 polymorphisms in the development of ACPA-positive status in patients with RA. PMID- 26903442 TI - Five-year follow-up of radiographic sacroiliitis: progression as well as improvement? PMID- 26903443 TI - International Developments in the Care of Familial Hypercholesterolemia: Where Now and Where to Next? AB - Several international guidelines and consensus statements have recently been published on the care of familial hypercholesterolemia (FH)(1-3)). They agree on approaches to case detection and cascade testing, protocols in children, lifestyle and drug treatment strategies, and indications for lipoprotein apheresis. However, most countries in the world still do not have integrated, systematic FH screening programs to adequately detect and treat cases in the community. This study provides a comprehensive overview of recent and future international initiatives for closing the gaps in the care of FH. PMID- 26903444 TI - Inhibitory effects of Aphanizomenon flos-aquae constituents on human UDP-glucose dehydrogenase activity. AB - OBJECTIVE: The purpose of this study was to investigate the in vitro inhibitory effects of the edible microalga Aphanizomenon flos-aquae (AFA) on human UDP-alpha d-glucose 6-dehydrogenase (UGDH) activity, a cytosolic enzyme involved both in tumor progression and in phytochemical bioavailability. METHODS: Both the hydrophilic and ethanolic AFA extracts as well as the constitutive active principles phycocyanin (PC), phycocyanobilin (PCB) and mycosporine-like amino acids (MAAs) were tested. RESULTS: Among AFA components, PCB presented the strongest inhibitory effect on UGDH activity, acting as a competitive inhibitor with respect to UDP-glucose and a non-competitive inhibitor with respect to NAD(+). In preliminary experiments, AFA PCB was also effective in reducing the colony formation capacity of PC-3 prostate cancer cells and FTC-133 thyroid cancer cells. CONCLUSIONS: Overall, these findings confirmed that AFA and its active principles are natural compounds with high biological activity. Further studies evaluating the effects of AFA PCB in reducing tumor cell growth and phytochemical glucuronidation are encouraged. PMID- 26903447 TI - Is there a role for patient-controlled analgesia in the emergency department? PMID- 26903445 TI - Mitochondrial Biology and Neurological Diseases. AB - Mitochondria are extremely active organelles that perform a variety of roles in the cell including energy production, regulation of calcium homeostasis, apoptosis, and population maintenance through fission and fusion. Mitochondrial dysfunction in the form of oxidative stress and mutations can contribute to the pathogenesis of various neurodegenerative diseases such as Parkinson's (PD), Alzheimer's (AD), and Huntington's diseases (HD). Abnormalities of Complex I function in the electron transport chain have been implicated in some neurodegenerative diseases, inhibiting ATP production and generating reactive oxygen species that can cause major damage to mitochondria. Mutations in both nuclear and mitochondrial DNA can contribute to neurodegenerative disease, although the pathogenesis of these conditions tends to focus on nuclear mutations. In PD, nuclear genome mutations in the PINK1 and parkin genes have been implicated in neurodegeneration [1], while mutations in APP, PSEN1 and PSEN2 have been implicated in a variety of clinical symptoms of AD [5]. Mutant htt protein is known to cause HD [2]. Much progress has been made to determine some causes of these neurodegenerative diseases, though permanent treatments have yet to be developed. In this review, we discuss the roles of mitochondrial dysfunction in the pathogenesis of these diseases. PMID- 26903448 TI - Clinical leadership and quality improvement: vital for good health care. PMID- 26903450 TI - Tracheostomies for the non-expert 1: indications and techniques. AB - Recent reports have emphasized shortcomings in routine and emergency care leading to adverse outcomes in patients with tracheostomies. This two-part article provides a guide to the principles of care for staff looking after adult patients with tracheostomies in the hospital. The first part looks at indications and techniques. PMID- 26903446 TI - Kappa Opioids, Salvinorin A and Major Depressive Disorder. AB - Opioids are traditionally associated with pain, analgesia and drug abuse. It is now clear, however, that the opioids are central players in mood. The implications for mood disorders, particularly clinical depression, suggest a paradigm shift from the monoamine neurotransmitters to the opioids either alone or in interaction with monoamine neurons. We have a special interest in dynorphin, the last of the major endogenous opioids to be isolated and identified. Dynorphin is derived from the Greek word for power, dynamis, which hints at the expectation that the neuropeptide held for its discoverers. Yet, dynorphin and its opioid receptor subtype, kappa, has always taken a backseat to the endogenous b-endorphin and the exogenous morphine that both bind the mu opioid receptor subtype. That may be changing as the dynorphin/ kappa system has been shown to have different, often opposite, neurophysiological and behavioral influences. This includes major depressive disorder (MDD). Here, we have undertaken a review of dynorphin/ kappa neurobiology as related to behaviors, especially MDD. Highlights include the unique features of dynorphin and kappa receptors and the special relation of a plant-based agonist of the kappa receptor salvinorin A. In addition to acting as a kappa opioid agonist, we conclude that salvinorin A has a complex pharmacologic profile, with potential additional mechanisms of action. Its unique neurophysiological effects make Salvinorina A an ideal candidate for MDD treatment research. PMID- 26903451 TI - Iatrogenic greenhouse gases: the role of anaesthetic agents. AB - The contribution of health-care activity to climate change is not negligible and is increasing. Anaesthetic greenhouse gases, in particular the fluranes, have a much more potent global warming capacity, volume for volume, than carbon dioxide, but their emissions remain completely unregulated. PMID- 26903452 TI - Anaesthesia for laparoscopic surgery. AB - Laparoscopic surgery has become increasingly common with reduced postoperative pain and faster recovery. Clinicians managing patients undergoing abdominal laparoscopic surgery should appreciate the physiological changes which mainly arise from patient positioning and the effects of pneumoperitoneum. PMID- 26903453 TI - Assessment of frailty in the inpatient setting. AB - Frailty is a common condition which results in increased risk of adverse outcomes following hospital admission. This review looks at how to identify, assess and manage frail patients in the inpatient setting. PMID- 26903454 TI - Management of Barrett's oesophagus. AB - Barrett's oesophagus is associated with the development of oesophageal adenocarcinoma. This review highlights the management strategies currently used in the treatment of this condition. PMID- 26903455 TI - Genetic testing in Marfan syndrome. AB - Genetic testing is aiding rapid diagnosis of Marfan syndrome as a basis for management of eye, heart and skeletal disease. The affected patient's mutation can be used as a basis for prenatal or postnatal diagnosis of offspring. Preimplantation genetic diagnosis, the technique of choice, can ensure an unaffected pregnancy. PMID- 26903456 TI - Patients' and health-care professionals' awareness of cost: a multicentre survey. AB - Delivering cost-effective health care within the constraints of public funding is the goal of the NHS. In this study 248 health-care professionals and patients across six different hospitals were surveyed to ascertain their cost awareness. Cost awareness was poor across all groups. PMID- 26903457 TI - A feverish junior doctor with a diagnosis not to be missed. PMID- 26903458 TI - Sensory neuronopathy as a possible paraneoplastic neurological syndrome linked with pancreatic cancer. PMID- 26903459 TI - Acute interstitial nephritis caused by two different proton pump inhibitors. PMID- 26903460 TI - Dark necrotic mucosa in sinonasal mucormycosis. PMID- 26903461 TI - Sir Frederick Hewitt, pioneer anaesthetist. PMID- 26903462 TI - Choosing wisely. PMID- 26903464 TI - Should we reconsider the use of intra-articular local anaesthetics? PMID- 26903466 TI - Human factor skills in the surgical environment. PMID- 26903465 TI - Managing blood glucose levels in patients with diabetes and renal impairment. PMID- 26903467 TI - Clinical assessment of patients with thyroid eye disease. PMID- 26903468 TI - Management of patients with thyroid eye disease. PMID- 26903469 TI - Mycobacterium sherrisii visceral disseminated infection in an African HIV infected adolescent. AB - A case of visceral disseminated infection by Mycobacterium sherrisii in an African HIV-infected adolescent with multiple abdominal abscesses is reported. Despite multiple drug resistance to first-line antibiotics in vitro, long-term treatment with clarithromycin, moxifloxacin, and clindamycin, together with appropriate antiretroviral treatment, resulted in clinical and radiological cure after 19 months of therapy and follow-up. PMID- 26903470 TI - A rare case of a giant saphenous vein graft aneurysm with right atrial fistula formation. AB - A 57-year-old hypertensive and dyslipidaemic man with a history of coronary artery bypass graft 19 years previously, presented with severe exertional angina and dyspnoea despite optimal anti-ischaemic pharmacological therapy and previous percutaneous coronary intervention to the left circumflex artery. CT revealed an aneurysm of the saphenous vein graft to the posterior left ventricular branch of the right coronary artery. The aneurysm had formed a fistulous connection with the right atrium. Initially, luminal reconstruction with serial stents was deemed the most appropriate treatment strategy. However, the procedure was abandoned due to the inability to visualise the graft distal to the aneurysm and the significant shunt to the right atrium. Surgical correction of the right atrial wall defect and replacement of the diseased grafts led to complete resolution of the patient's symptoms. PMID- 26903471 TI - Aneurysm of an anomalous splenic artery arising from splenomesentric trunk: a rare presentation. PMID- 26903472 TI - Size determination and quantification of engineered cerium oxide nanoparticles by flow field-flow fractionation coupled to inductively coupled plasma mass spectrometry. AB - Facing the lack of studies on characterization and quantification of cerium oxide nanoparticles (CeO2 NPs), whose consumption and release is greatly increasing, this work proposes a method for their sizing and quantification by Flow Field flow Fractionation (FFFF) coupled to Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). Two modalities of FFFF (Asymmetric Flow- and Hollow Fiber-Flow Field Flow Fractionation, AF4 and HF5, respectively) are compared, and their advantages and limitations discussed. Experimental conditions (carrier composition, pH, ionic strength, crossflow and carrier flow rates) are studied in detail in terms of NP separation, recovery, and repeatability. Size characterization of CeO2 NPs was addressed by different approaches. In the absence of feasible size standards of CeO2 NPs, suspensions of Ag, Au, and SiO2 NPs of known size were investigated. Ag and Au NPs failed to show a comparable behavior to that of the CeO2 NPs, whereas the use of SiO2 NPs provided size estimations in agreement to those predicted by the theory. The latter approach was thus used for characterizing the size of CeO2 NPs in a commercial suspension. Results were in adequate concordance with those achieved by transmission electron microscopy, X-ray diffraction and dynamic light scattering. The quantification of CeO2 NPs in the commercial suspension by AF4-ICP-MS required the use of a CeO2 NPs standards, since the use of ionic cerium resulted in low recoveries (99 +/- 9% vs. 73 +/- 7%, respectively). A limit of detection of 0.9 MUg L(-1) CeO2 corresponding to a number concentration of 1.8 * 1012 L(-1) for NPs of 5 nm was achieved for an injection volume of 100 MUL. PMID- 26903473 TI - Small synthetic ligands for the enrichment of viral particles pseudotyped with amphotropic murine leukemia virus envelope. AB - Retroviral vectors gained popularity toward other viral vectors as they integrate their genome into hosts' genome, a characteristic required for the modification of stem cells. However, the production of viable particles for gene therapy is hampered by the low ratio of infectious to non-infectious viral particles after purification, low titers and limited number of competent viral receptors. We have developed de novo two fully synthetic triazine-based ligands that can selectively bind retroviral particles pseudotyped with amphotropic murine leukemia virus envelope (AMPHO4070A). A 78-membered library of triazine-based ligands was designed in silico and was virtually screened against the modeled structure of the AMPHO4070A protein. Ligands displaying the highest energy of binding were synthesized on cross-linked agarose and experimentally tested. Adsorbents containing ligands A5A10 and A10A11 showed selectivity toward viral particles containing the target protein (VLP-AMPHO), binding 19 +/- 5 MUg/g support and 47 +/- 13 MUg/g support, respectively. The elution conditions for both ligands were mild and with high recovery yields (80-100%), in comparison with common purification practices. These results were based on a lab-scale experimental setting with VLP integrity being confirmed through TEM. In particular, the elution buffer containing 12 mM imidazole allowed the recovery of intact amphotropic viral particles. PMID- 26903474 TI - Ebola epidemic of 2014-2015: unresolved ethical issues. AB - Some ethical aspects of the management of the Ebola epidemic in Guinea, Liberia and Sierra Leone which started in January 2014, have been questionable. First, as regards the prevention of the spread of the virus, the necessary epidemiological investigations on the origin of the infection were not carried out adequately and this did not help to curb the spread of the disease. A disparity has been observed between the western and African countries' access to the treatment of patients; this infringes on the principle of equality. This paper also focuses on how the Global Public Goods for Health principle was not fully respected in the management of the epidemic. PMID- 26903475 TI - Type 1 diabetes associated autoimmunity. AB - Diabetes mellitus is increasing in prevalence worldwide. The economic costs are considerable given the cardiovascular complications and co-morbidities that it may entail. Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by the loss of insulin-producing pancreatic beta-cells. The pathogenesis of T1D is complex and multifactorial and involves a genetic susceptibility that predisposes to abnormal immune responses in the presence of ill-defined environmental insults to the pancreatic islets. Genetic background may affect the risk for autoimmune disease and patients with T1D exhibit an increased risk of other autoimmune disorders such as autoimmune thyroid disease, Addison's disease, autoimmune gastritis, coeliac disease and vitiligo. Approximately 20%-25% of patients with T1D have thyroid antibodies, and up to 50% of such patients progress to clinical autoimmune thyroid disease. Approximately 0.5% of diabetic patients have concomitant Addison's disease and 4% have coeliac disease. The prevalence of autoimmune gastritis and pernicious anemia is 5% to 10% and 2.6% to 4%, respectively. Early detection of antibodies and latent organ-specific dysfunction is advocated to alert physicians to take appropriate action in order to prevent full-blown disease. Patients and family members should be educated to be able to recognize signs and symptoms of underlying disease. PMID- 26903477 TI - Stick-Slip Friction of PDMS Surfaces for Bioinspired Adhesives. AB - Friction plays an important role in the adhesion of many climbing organisms, such as the gecko. During the shearing between two surfaces, periodic stick-slip behavior is often observed and may be critical to the adhesion of gecko setae and gecko-inspired adhesives. Here, we investigate the influence of short oligomers and pendent chains on the stick-slip friction of polydimethylsiloxane (PDMS), a commonly used material for bioinspired adhesives. Three different stick-slip patterns were observed on these surfaces (flat or microstructured) depending on the presence or absence of oligomers and their ability to diffuse out of the material. After washing samples to remove any untethered oligomeric chains, or after oxygen plasma treatment to convert the surface to a thin layer of silica, we decouple the contributions of stiffness, oligomers, and pendant chains to the stick-slip behavior. The stick phase is mainly controlled by the stiffness while the amount of untethered oligomers and pendant chains available at the contact interface defines the slip phase. A large amount of oligomers and pendant chains resulted in a large slip time, dominating the period of stick-slip motion. PMID- 26903476 TI - Comparison of idiopathic (isolated) aortitis and giant cell arteritis-related aortitis. A French retrospective multicenter study of 117 patients. AB - OBJECTIVES: The aim of the study was to compare clinical/imaging findings and outcome in patients with idiopathic (isolated aortitis, IA) and with giant cell arteritis (GCA)-related aortitis. METHODS: Patients from 11 French internal medicine departments were retrospectively included. Aortitis was defined by aortic wall thickening >2mm and/or an aortic aneurysm on CT-scan, associated to inflammatory syndrome. Patients with GCA had at least 3 ACR criteria. Aortic events (aneurysm, dissection, aortic surgeries) were reported, and free of aortic events-survival were compared. RESULTS: Among 191 patients with non-infectious aortitis, 73 with GCA and 44 with IA were included. Patients with IA were younger (65 vs 70 years, p=0.003) and comprised more past/current smokers (43 vs 15%, p=0.0007). Aortic aneurisms were more frequent (38% vs 20%, p=0.03), and aortic wall thickening was more pronounced in IA. During follow-up (median=34 months), subsequent development of aortic aneurysm was significantly lower in GCA when compared to IA (p=0.009). GCA patients required significantly less aortic surgery during follow-up than IA patients (p=0.02). Mean age, sex ratio, inflammatory parameters, and free of aortic aneurism survival were equivalent in patients with IA >= 60 years when compared to patients with GCA-related aortitis. CONCLUSIONS: IA is more severe than aortitis related to GCA, with higher proportions of aortic aneurism at diagnosis and during follow-up. IA is a heterogeneous disease and its prognosis is worse in younger patients <60 years. Most patients with IA >= 60 years share many features with GCA-related aortitis. PMID- 26903478 TI - PF4-heparin antibodies during ECMO: incidence, course, and outcomes. PMID- 26903479 TI - Shortened Intervals during Heterologous Boosting Preserve Memory CD8 T Cell Function but Compromise Longevity. AB - Developing vaccine strategies to generate high numbers of Ag-specific CD8 T cells may be necessary for protection against recalcitrant pathogens. Heterologous prime-boost-boost immunization has been shown to result in large quantities of functional memory CD8 T cells with protective capacities and long-term stability. Completing the serial immunization steps for heterologous prime-boost-boost can be lengthy, leaving the host vulnerable for an extensive period of time during the vaccination process. We show in this study that shortening the intervals between boosting events to 2 wk results in high numbers of functional and protective Ag-specific CD8 T cells. This protection is comparable to that achieved with long-term boosting intervals. Short-boosted Ag-specific CD8 T cells display a canonical memory T cell signature associated with long-lived memory and have identical proliferative potential to long-boosted T cells Both populations robustly respond to antigenic re-exposure. Despite this, short-boosted Ag specific CD8 T cells continue to contract gradually over time, which correlates to metabolic differences between short- and long-boosted CD8 T cells at early memory time points. Our studies indicate that shortening the interval between boosts can yield abundant, functional Ag-specific CD8 T cells that are poised for immediate protection; however, this is at the expense of forming stable long-term memory. PMID- 26903481 TI - Mouse Cytomegalovirus Infection in BALB/c Mice Resembles Virus-Associated Secondary Hemophagocytic Lymphohistiocytosis and Shows a Pathogenesis Distinct from Primary Hemophagocytic Lymphohistiocytosis. AB - Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening immunological disorder that is characterized by systemic inflammation, widespread organ damage, and hypercytokinemia. Primary HLH is caused by mutations in granule-mediated cytotoxicity, whereas secondary HLH occurs, without a known genetic background, in a context of infections, malignancies, or autoimmune and autoinflammatory disorders. Clinical manifestations of both HLH subtypes are often precipitated by a viral infection, predominantly with Herpesviridae. Exploiting this knowledge, we established an animal model of virus-associated secondary HLH by infecting immunocompetent wild-type mice with the beta-herpesvirus murine CMV. C57BL/6 mice developed a mild inflammatory phenotype, whereas BALB/c mice displayed the clinicopathologic features of HLH, as set forth in the Histiocyte Society diagnostic guidelines: fever, cytopenia, hemophagocytosis, hyperferritinemia, and elevated serum levels of soluble CD25. BALB/c mice also developed lymphadenopathy, liver dysfunction, and decreased NK cell numbers. Lymphoid and myeloid cells were in a hyperactivated state. Nonetheless, depletion of CD8(+) T cells could not inhibit or cure the HLH-like syndrome, highlighting a first dissimilarity from mouse models of primary HLH. Immune cell hyperactivation in BALB/c mice was accompanied by a cytokine storm. Notably, plasma levels of IFN gamma, a key pathogenic cytokine in models of primary HLH, were the highest. Nevertheless, murine CMV-infected IFN-gamma-deficient mice still developed the aforementioned HLH-like symptoms. In fact, IFN-gamma-deficient mice displayed a more complete spectrum of HLH, including splenomegaly, coagulopathy, and decreased NK cell cytotoxicity, indicating a regulatory role for IFN-gamma in the pathogenesis of virus-associated secondary HLH as opposed to its central pathogenic role in primary HLH. PMID- 26903480 TI - T-bet Promotes Acute Graft-versus-Host Disease by Regulating Recipient Hematopoietic Cells in Mice. AB - Beyond its critical role in T cells, T-bet regulates the functions of APCs including dendritic cells and B cells, as well as NK cells. Given that recipient APCs are essential for priming allogeneic T cells and recipient NK or T cells are able to reject allogeneic donor cells, we evaluated the role of T-bet on the host in acute graft-versus-host disease (GVHD) using murine models of allogeneic bone marrow transplantation. T-bet(-/-) recipients developed significantly milder GVHD than their wild type counterparts in MHC-mismatched or CD4-dependent minor histocompatibility Ag-mismatched models. Allogeneic donor T cells, in particular, CD4 subset, significantly reduced IFN-gamma production, proliferation and migration, and caused less injury in liver and gut of T-bet(-/-) recipients. We further observed that T-bet on recipient hematopoietic cells was primarily responsible for the donor T cell response and pathogenicity in GVHD. T-bet(-/-) dendritic cells expressed higher levels of Trail, whereas they produced lower levels of IFN-gamma and IL-12/23 p40, as well as chemokine CXCL9, resulting in significantly higher levels of apoptosis, less priming, and infiltration of donor T cells. Meanwhile, NK cells in T-bet(-/-) hosts partially contribute to the decreased donor T cell proliferation. Furthermore, although T-bet on hematopoietic cells was required for GVHD development, it was largely dispensable for the graft-versus-leukemia effect. Taken together with our previous findings, we propose that T-bet is a potential therapeutic target for the control of GVHD through regulating donor T cells and recipient hematopoietic cells. PMID- 26903482 TI - Cutting Edge: Engineering Active IKKbeta in T Cells Drives Tumor Rejection. AB - Acquired dysfunction of tumor-reactive T cells is one mechanism by which tumors can evade the immune system. Identifying and correcting pathways that contribute to such dysfunction should enable novel anticancer therapy design. During cancer growth, T cells show reduced NF-kappaB activity, which is required for tumor rejection. Impaired T cell-intrinsic NF-kappaB may create a vicious cycle conducive to tumor progression and further T cell dysfunction. We hypothesized that forcing T cell-intrinsic NF-kappaB activation might break this cycle and induce tumor elimination. NF-kappaB was activated in T cells by inducing the expression of a constitutively active form of the upstream activator IkappaB kinase beta (IKKbeta). T cell-restricted constitutively active IKKbeta augmented the frequency of functional tumor-specific CD8(+) T cells and improved tumor control. Transfer of constitutively active IKKbeta-transduced T cells also boosted endogenous T cell responses that controlled pre-established tumors. Our results demonstrate that driving T cell-intrinsic NF-kappaB can result in tumor control, thus identifying a pathway with potential clinical applicability. PMID- 26903483 TI - Anticommensal Responses Are Associated with Regulatory T Cell Defect in Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy Patients. AB - Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a monogenic autoimmune disease caused by mutations in the AIRE gene. Although mainly an endocrine disease, a substantial fraction of patients have gastrointestinal manifestations. In this study, we have examined the role of anticommensal responses and their regulation. APECED patients had increased levels of Abs against Saccharomyces cerevisiae (p < 0.0001) and against several species of commensal gut bacteria, but not against species predominantly associated with other locations. The anticommensal Ab levels did not correlate with gastrointestinal autoantibodies, neutralizing anti-IL-17 or -IL-22 Abs, or gastrointestinal symptoms, although scarcity of the available clinical data suggests that further study is required. However, the anti-S. cerevisiae Ab levels showed a significant inverse correlation with FOXP3 expression levels in regulatory T cells (Treg), previously shown to be dysfunctional in APECED. The correlation was strongest in the activated CD45RO(+) population (rho = -0.706; p < 0.01). APECED patients also had decreased numbers of FOXP3(+) cells in gut biopsies. These results show that APECED patients develop early and sustained responses to gut microbial Ags in a pattern reminiscent of Crohn's disease. This abnormal immune recognition of gut commensals is linked to a systemic Treg defect, which is also reflected as a local decrease of gut-associated Treg. To our knowledge, these data are the first to show dysregulated responses to non self commensal Ags in APECED and indicate that AIRE contributes to the regulation of gut homeostasis, at least indirectly. The data also raise the possibility of persistent microbial stimulation as a contributing factor in the pathogenesis of APECED. PMID- 26903484 TI - Systematic Review of the Effects of Interventions to Promote Peer Interactions for Children who use Aided AAC. AB - The goals of this systematic review were to investigate studies that implemented interventions to increase or improve peer interaction for children who used aided AAC, to evaluate the strengths and limitations of those studies, and to discuss implications for practice and directions for future research. A systematic search resulted in the identification of 19 studies (56 participants). Studies were coded and summarized in terms of participants, independent and dependent variables, outcomes, and quality of evidence. All 19 studies reported positive effects on interactions with peers, though the results varied in degree. Although the quality of evidence varied, three studies met the standards of conclusive evidence, and an additional five presented preponderant evidence. The most frequently used intervention components were teaching children with complex communication needs how to use AAC within social interactions and teaching peers skills and strategies to promote interaction. While the body of research suggests that intervention can promote positive peer interactions for children with complex communication needs, the evidence for preschool-aged children and children with autism spectrum disorders is relatively sparse. PMID- 26903485 TI - Can Seeding in the Clinic Reach a Wide Audience? A Proof of Concept Study on Spreading a Health Message About Juvenile Idiopathic Arthritis Using a Shareable Online Video. AB - BACKGROUND: Shareable online video offers the potential for spreading a health message across online and real world social networks. Seeding a message in a clinical setting may be advantageous. OBJECTIVE: To investigate the potential of an online video to spread a health message about juvenile idiopathic arthritis (JIA) when delivered or seeded in a clinical setting and investigate factors that influence sharing behavior. METHODS: Multimethod proof of concept study. Concepts for two different styles of video were developed using focus groups and interviews and reviewed by an online market research panel. We compared dissemination of the two videos from two specialist pediatric rheumatology clinics in NHS Hospitals. Participants were 15 patients, family members, and clinical staff with knowledge of JIA at concept stage; 300 market research panel members in development stage; and 38 patients and their parents or guardians in the seeding stage. Newly diagnosed patients with JIA and/or parents or guardians were invited to view and share an online video with a health message about JIA across real-life and electronic social networks. Main outcome measures were viewing statistics, sharing behavior and patterns, and participant feedback. RESULTS: Of 38 patients and/or their parents or guardians given links, 26 visited the video webpage and shared the link, 2 visited and did not share, and 10 did not visit. Most links were viewed and shared within a few days. A total of 3314 pageviews were recorded with a mean of 89.6 pageviews per link (range 0-1245). Links were accessed from 26 countries, with most viewers in the United Kingdom (82.5%). Mothers were the most active group of sharers. CONCLUSIONS: Distribution of a video link in a clinical setting may be an effective way to spread a health message. Parents or guardians of children with JIA are more likely to share a link than young people. Dissemination depends on a small number of active sharers, the content of the video, and the willingness of participants to share health information about themselves. TRIAL REGISTRATION: UK Clinical Research Network Study Portfolio ID (UKCRN): 13747; http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=13747 (Archived by WebCite at http://www.webcitation.org/6eeXlMmM6). PMID- 26903486 TI - Acute effects of inspiratory muscle warm-up on pulmonary function in healthy subjects. AB - The acute effects of inspiratory muscle warm-up on pulmonary functions were examined in 26 healthy male subjects using the pulmonary function test (PFT) in three different trials. The control trial (CON) did not involve inspiratory muscle warm-up, while the placebo (IMWp) and experimental (IMW) trials involved inspiratory muscle warm-up. There were no significant changes between the IMWp and CON trials (p>0.05). All the PFT measurements, including slow vital capacity, inspiratory vital capacity, forced vital capacity, forced expiratory volume in one second, maximal voluntary ventilation, and maximal inspiratory pressure were significantly increased by 3.55%, 12.52%, 5.00%, 2.75%, 2.66%, and 7.03% respectively, in the subjects in the IMW trial than those in the CON trial (p<0.05). These results show that inspiratory muscle warm-up improved the pulmonary functions. The mechanisms responsible for these improvements are probably associated with the concomitant increase in the inspiratory muscle strength, and the cooperation of the upper thorax, neck, and respiratory muscles, and increased level of reactive O2 species in muscle tissue, and potentially improvement of muscle O2 delivery-to-utilization. However, further investigation is required to determine the precise mechanisms responsible from among these candidates. PMID- 26903487 TI - Testing the 'microbubble effect' using the Cavitron technique to measure xylem water extraction curves. AB - Plant resistance to xylem cavitation is a major drought adaptation trait and is essential to characterizing vulnerability to climate change. Cavitation resistance can be determined with vulnerability curves. In the past decade, new techniques have increased the ease and speed at which vulnerability curves are produced. However, these new techniques are also subject to new artefacts, especially as related to long-vesselled species. We tested the reliability of the 'flow rotor' centrifuge technique, the so-called Cavitron, and investigated one potential mechanism behind the open vessel artefact in centrifuge-based vulnerability curves: the microbubble effect. The microbubble effect hypothesizes that microbubbles introduced to open vessels, either through sample flushing or injection of solution, travel by buoyancy or mass flow towards the axis of rotation where they artefactually nucleate cavitation. To test the microbubble effect, we constructed vulnerability curves using three different rotor sizes for five species with varying maximum vessel length, as well as water extraction curves that are constructed without injection of solution into the rotor. We found that the Cavitron technique is robust to measure resistance to cavitation in tracheid-bearing and short-vesselled species, but not for long-vesselled ones. Moreover, our results support the microbubble effect hypothesis as the major cause for the open vessel artefact in long-vesselled species. PMID- 26903488 TI - Range expansion of invasive shrubs: implication for crown fire risk in forestlands of the southern USA. AB - Non-native plant invasions and changing management activities have dramatically altered the structure and composition of forests worldwide. Invasive shrubs and fire suppression have led to increased densification and biomass accumulation in forest ecosystems of the southeastern USA. Notably, Chinese and European privets are rapid growing, shade-tolerant shrubs which number among the most aggressive invasive species in these forests. Privet encroachment has caused losses of native diversity, alteration of ecosystem processes and changes in community structure. The latter has become manifest through decreases in fine herbaceous fuels concurrent with increases in coarse woody fuels in forest understoreys. These alterations in fuel structure will potentially lead to less frequent, but more severe forest fires, which threaten important forest resources during extreme weather conditions. Drawing on extensive data sets compiled by the US Forest Service, we integrated statistical forecasting and analytical techniques within a spatially explicit, agent-based, simulation framework to predict potential range expansion of Chinese and European privet (Ligustrum sinenseandL. vulgare) and the associated increase in crown fire risk over the next two decades in forestlands of Mississippi and Alabama. Our results indicate that probability of invasion is positively associated with elevation, adjacency (within 300 m) to water bodies, mean daily maximum temperature, site productivity and private land ownership, and is negatively associated with slope, stand age, artificial regeneration, distance to the nearest road and fire disturbance. Our projections suggest the total area invaded will increase from 1.36 to ~31.39% of all forestlands in Mississippi and Alabama (~7 million hectares) and the annual frequency of crown fires in these forestlands will approximately double within the next two decades. Such time series projections of annual range expansions and crown fire frequency should provide land managers and restoration practitioners with an invasion chronology upon which to base proactive management plans. PMID- 26903489 TI - Recovered recall memory after decompression of the fornix by surgical removal of pineal tumor. PMID- 26903490 TI - Focal seizure symptoms in idiopathic generalized epilepsies. PMID- 26903491 TI - The unruptured intracranial aneurysm treatment score: A multidisciplinary consensus. PMID- 26903492 TI - Practice Guideline: Idiopathic normal pressure hydrocephalus: Response to shunting and predictors of response: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. PMID- 26903493 TI - Mystery Case: Neurocutaneous melanosis with diffuse leptomeningeal malignant melanoma in an adult. PMID- 26903494 TI - Clinical Reasoning: A neonate with micrognathia and hypotonia. PMID- 26903495 TI - Erratum. PMID- 26903496 TI - Beyond the Central Dogma: Model-Based Learning of How Genes Determine Phenotypes. AB - In an introductory biology course, we implemented a learner-centered, model-based pedagogy that frequently engaged students in building conceptual models to explain how genes determine phenotypes. Model-building tasks were incorporated within case studies and aimed at eliciting students' understanding of 1) the origin of variation in a population and 2) how genes/alleles determine phenotypes. Guided by theory on hierarchical development of systems-thinking skills, we scaffolded instruction and assessment so that students would first focus on articulating isolated relationships between pairs of molecular genetics structures and then integrate these relationships into an explanatory network. We analyzed models students generated on two exams to assess whether students' learning of molecular genetics progressed along the theoretical hierarchical sequence of systems-thinking skills acquisition. With repeated practice, peer discussion, and instructor feedback over the course of the semester, students' models became more accurate, better contextualized, and more meaningful. At the end of the semester, however, more than 25% of students still struggled to describe phenotype as an output of protein function. We therefore recommend that 1) practices like modeling, which require connecting genes to phenotypes; and 2) well-developed case studies highlighting proteins and their functions, take center stage in molecular genetics instruction. PMID- 26903497 TI - Development of the Statistical Reasoning in Biology Concept Inventory (SRBCI). AB - We followed established best practices in concept inventory design and developed a 12-item inventory to assess student ability in statistical reasoning in biology (Statistical Reasoning in Biology Concept Inventory [SRBCI]). It is important to assess student thinking in this conceptual area, because it is a fundamental requirement of being statistically literate and associated skills are needed in almost all walks of life. Despite this, previous work shows that non-expert-like thinking in statistical reasoning is common, even after instruction. As science educators, our goal should be to move students along a novice-to-expert spectrum, which could be achieved with growing experience in statistical reasoning. We used item response theory analyses (the one-parameter Rasch model and associated analyses) to assess responses gathered from biology students in two populations at a large research university in Canada in order to test SRBCI's robustness and sensitivity in capturing useful data relating to the students' conceptual ability in statistical reasoning. Our analyses indicated that SRBCI is a unidimensional construct, with items that vary widely in difficulty and provide useful information about such student ability. SRBCI should be useful as a diagnostic tool in a variety of biology settings and as a means of measuring the success of teaching interventions designed to improve statistical reasoning skills. PMID- 26903498 TI - Contemporary Test Validity in Theory and Practice: A Primer for Discipline-Based Education Researchers. AB - Most discipline-based education researchers (DBERs) were formally trained in the methods of scientific disciplines such as biology, chemistry, and physics, rather than social science disciplines such as psychology and education. As a result, DBERs may have never taken specific courses in the social science research methodology--either quantitative or qualitative--on which their scholarship often relies so heavily. One particular aspect of (quantitative) social science research that differs markedly from disciplines such as biology and chemistry is the instrumentation used to quantify phenomena. In response, this Research Methods essay offers a contemporary social science perspective on test validity and the validation process. The instructional piece explores the concepts of test validity, the validation process, validity evidence, and key threats to validity. The essay also includes an in-depth example of a validity argument and validation approach for a test of student argument analysis. In addition to DBERs, this essay should benefit practitioners (e.g., lab directors, faculty members) in the development, evaluation, and/or selection of instruments for their work assessing students or evaluating pedagogical innovations. PMID- 26903499 TI - Frequency and aetiology of hypercalcaemia. AB - BACKGROUND: Hypercalcaemia is rare in children and may present with characteristic signs/symptoms or coincidentally following investigations for a variety of non-specific conditions. The aetiologies of childhood hypercalcaemia are diverse. Untreated sustained hypercalcaemia has serious clinical consequences. However there is limited data regarding the true frequency and aetiologies of childhood hypercalcaemia. AIM: To determine the frequency of severe childhood hypercalcaemia in routine clinical practice. METHODS: The laboratory database was searched for all children (0-17 years) with severe hypercalcaemia defined as non-adjusted >=2.90 mmol/L from 2007-2012. Hypercalcaemia was categorised as either transient (1 day) or sustained (>=2 consecutive days). Retrospective analysis of all cases of sustained severe hypercalcaemia was performed to identify the underlying aetiology. RESULTS: Over the 5 year period, 206 children were identified as severely hypercalcaemic >=2.90 mmol/L (0.3% all 61,380 calcium requests). Of these 131 (63.3%) children were classified as having sustained hypercalcaemia. The frequency of severe hypercalcaemia was highest in neonates (42% of sustained cases) and was inversely related to age. Sepsis was the most common aetiology (24%), particularly in neonates where it accounted for 41% of all causes of neonatal hypercalcaemia. Endocrine aetiologies included congenital adrenal hyperplasia (2 cases), fat necrosis (1), Addison's disease (2). A genetic cause was identified in 3 children (2 familial hypocalciuria hypercalcaemia, 1 Williams syndrome). CONCLUSIONS: Sustained hypercalcaemia affects 1 in 500 children in a general hospital setting. The frequency was highest in neonates and underlying aetiology differed markedly with age. All children with sustained hypercalcaemia require thorough investigation to determine the underlying aetiology to ensure appropriate management. PMID- 26903500 TI - Oxidative Stress in Youth and Adolescents With Elevated Body Mass Index Exposed to Secondhand Smoke. AB - INTRODUCTION: Our objective was to investigate the relationships between secondhand smoke (SHS) exposure and oxidative stress in a group of youth and adolescents with elevated body mass index. METHODS: Participants in this cross sectional study were healthy nonsmoking youth and adolescents ages 9 to 18 years old. Three-quarters of the participants were either overweight or obese. SHS exposure was determined by survey and hair nicotine level. Markers of oxidation were total antioxidant capacity and protein malondialdehyde adducts (MDA). RESULTS: Ninety subjects were studied; adequate hair samples were available for 86. The mean hair nicotine level was 0.75ng/mg, the median was 0.58ng/mg and the range was 0.09-2.88ng/mg. There was a significant relationship between MDA and the three survey questions regarding smoke exposure ([mother smokes, r = 0.29, P = .006], [smoker lives in the home, r = 0.31, P = .004], and [number of smokers in the home, r = 0.36, P = .002]). There was a significant positive relationship between log-hair nicotine and MDA (Pearson r = 0.233, P = .031), which remained significant after controlling for age, sex, race, and method of insurance. No relationship was found between log-hair nicotine and total antioxidant capacity. However, there was a significant relationship between number of smokers in the home (r = 0.24, P = .042) and total antioxidant capacity. CONCLUSIONS: We have demonstrated a significant positive relationship hair nicotine level and MDA in a group of youth with a high proportion of overweight/obese subjects. IMPLICATIONS: We have shown a significant relationship between objectively measured SHS exposure and one marker of oxidative stress in a sample of youth and adolescents with a high proportion of overweight/obese subjects, and who were nonsmokers with relatively low tobacco exposure. This finding remains significant after controlling for age, sex, race, and type of medical insurance. Since the cardiovascular effects of SHS exposure are related to oxidative stress, this finding adds to our knowledge that the sequence of deleterious effects of tobacco exposure on the cardiovascular system begins long before clinical disease is evident. PMID- 26903501 TI - Grainyhead-like 2 downstream targets act to suppress epithelial-to-mesenchymal transition during neural tube closure. AB - The transcription factor grainyhead-like 2 (GRHL2) is expressed in non-neural ectoderm (NNE) and Grhl2 loss results in fully penetrant cranial neural tube defects (NTDs) in mice. GRHL2 activates expression of several epithelial genes; however, additional molecular targets and functional processes regulated by GRHL2 in the NNE remain to be determined, as well as the underlying cause of the NTDs in Grhl2 mutants. Here, we find that Grhl2 loss results in abnormal mesenchymal phenotypes in the NNE, including aberrant vimentin expression and increased cellular dynamics that affects the NNE and neural crest cells. The resulting loss of NNE integrity contributes to an inability of the cranial neural folds to move toward the midline and results in NTD. Further, we identified Esrp1, Sostdc1, Fermt1, Tmprss2 and Lamc2 as novel NNE-expressed genes that are downregulated in Grhl2 mutants. Our in vitro assays show that they act as suppressors of the epithelial-to-mesenchymal transition (EMT). Thus, GRHL2 promotes the epithelial nature of the NNE during the dynamic events of neural tube formation by both activating key epithelial genes and actively suppressing EMT through novel downstream EMT suppressors. PMID- 26903503 TI - Retinoic acid-induced premature osteoblast-to-preosteocyte transitioning has multiple effects on calvarial development. AB - We have previously shown that, in human and zebrafish, hypomorphic mutations of the gene encoding the retinoic acid (RA)-metabolizing enzyme Cyp26b1 result in coronal craniosynostosis, caused by an RA-induced premature transitioning of suture osteoblasts to preosteocytes, inducing ectopic mineralization of the suture's osteoid matrix. In addition, we showed that human CYP26B1 null patients have more severe and seemingly opposite skull defects, characterized by smaller and fragmented calvaria, but the cellular basis of these defects remained largely unclear. Here, by treating juvenile zebrafish with exogenous RA or a chemical Cyp26 inhibitor in the presence or absence of osteogenic cells or bone-resorbing osteoclasts, we demonstrate that both reduced calvarial size and calvarial fragmentation are also caused by RA-induced premature osteoblast-to-preosteocyte transitioning. During calvarial growth, the resulting osteoblast deprival leads to decreased osteoid production and thereby smaller and thinner calvaria, whereas calvarial fragmentation is caused by increased osteoclast stimulation through the gained preosteocytes. Together, our data demonstrate that RA-induced osteoblast to-preosteocyte transitioning has multiple effects on developing bone in Cyp26b1 mutants, ranging from gain to loss of bone, depending on the allelic strength, the developmental stage and the cellular context. PMID- 26903504 TI - Mutations in the murine homologue of TUBB5 cause microcephaly by perturbing cell cycle progression and inducing p53-associated apoptosis. AB - Microtubules play a crucial role in the generation, migration and differentiation of nascent neurons in the developing vertebrate brain. Mutations in the constituents of microtubules, the tubulins, are known to cause an array of neurological disorders, including lissencephaly, polymicrogyria and microcephaly. In this study we explore the genetic and cellular mechanisms that cause TUBB5 associated microcephaly by exploiting two new mouse models: a conditional E401K knock-in, and a conditional knockout animal. These mice present with profound microcephaly due to a loss of upper-layer neurons that correlates with massive apoptosis and upregulation of p53. This phenotype is associated with a delay in cell cycle progression and ectopic DNA elements in progenitors, which is dependent on the dosage of functional Tubb5. Strikingly, we report ectopic Sox2 positive progenitors and defects in spindle orientation in our knock-in mouse line, which are absent in knockout animals. This work sheds light on the functional repertoire of Tubb5, reveals that the E401K mutation acts by a complex mechanism, and demonstrates that the cellular pathology driving TUBB5-associated microcephaly is cell death. PMID- 26903502 TI - EFN-4 functions in LAD-2-mediated axon guidance in Caenorhabditis elegans. AB - During development of the nervous system, growing axons rely on guidance molecules to direct axon pathfinding. A well-characterized family of guidance molecules are the membrane-associated ephrins, which together with their cognate Eph receptors, direct axon navigation in a contact-mediated fashion. InC. elegans, the ephrin-Eph signaling system is conserved and is best characterized for their roles in neuroblast migration during early embryogenesis. This study demonstrates a role for the C. elegans ephrin EFN-4 in axon guidance. We provide both genetic and biochemical evidence that is consistent with the C. elegans divergent L1 cell adhesion molecule LAD-2 acting as a non-canonical ephrin receptor to EFN-4 to promote axon guidance. We also show that EFN-4 probably functions as a diffusible factor because EFN-4 engineered to be soluble can promote LAD-2-mediated axon guidance. This study thus reveals a potential additional mechanism for ephrins in regulating axon guidance and expands the repertoire of receptors by which ephrins can signal. PMID- 26903506 TI - The Myb-domain protein ULTRAPETALA1 INTERACTING FACTOR 1 controls floral meristem activities in Arabidopsis. AB - Higher plants continuously and iteratively produce new above-ground organs in the form of leaves, stems and flowers. These organs arise from shoot apical meristems whose homeostasis depends on coordination between self-renewal of stem cells and their differentiation into organ founder cells. This coordination is stringently controlled by the central transcription factor WUSCHEL (WUS), which is both necessary and sufficient for stem cell specification in Arabidopsis thaliana ULTRAPETALA1 (ULT1) was previously identified as a plant-specific, negative regulator of WUS expression. However, molecular mechanisms underlying this regulation remain unknown. ULT1 protein contains a SAND putative DNA-binding domain and a B-box, previously proposed as a protein interaction domain in eukaryotes. Here, we characterise a novel partner of ULT1, named ULT1 INTERACTING FACTOR 1 (UIF1), which contains a Myb domain and an EAR motif. UIF1 and ULT1 function in the same pathway for regulation of organ number in the flower. Moreover, UIF1 displays DNA-binding activity and specifically binds to WUS regulatory elements. We thus provide genetic and molecular evidence that UIF1 and ULT1 work together in floral meristem homeostasis, probably by direct repression of WUS expression. PMID- 26903508 TI - Genome-wide analysis of spatiotemporal gene expression patterns during early embryogenesis in rice. AB - Embryogenesis in rice is different from that of most dicotolydonous plants in that it shows a non-stereotypic cell division pattern, formation of dorsal ventral polarity, and endogenous initiation of the radicle. To reveal the transcriptional features associated with developmental events during rice early embryogenesis, we used microarray analysis coupled with laser microdissection to obtain both spatial and temporal transcription profiles. Our results allowed us to determine spatial expression foci for each expressed gene in the globular embryo, which revealed the importance of phytohormone-related genes and a suite of transcription factors to early embryogenesis. Our analysis showed the polarized expression of a small number of genes along the apical-basal and dorsal ventral axes in the globular embryo, which tended to fluctuate in later developmental stages. We also analyzed gene expression patterns in the early globular embryo and how this relates to expression in embryonic organs at later stages. We confirmed the accuracy of the expression patterns found by microarray analysis of embryo subdomains using in situ hybridization. Our study identified homologous genes from Arabidopsis thaliana with known functions in embryogenesis in addition to unique and uncharacterized genes that show polarized expression patterns during embryogenesis. The results of this study are presented in a database to provide a framework for spatiotemporal gene expression during rice embryogenesis, to serve as a resource for future functional analysis of genes, and as a basis for comparative studies of plant embryogenesis. PMID- 26903507 TI - The coordination of ploidy and cell size differs between cell layers in leaves. AB - Growth and developmental processes are occasionally accompanied by multiple rounds of DNA replication, known as endoreduplication. Coordination between endoreduplication and cell size regulation often plays a crucial role in proper organogenesis and cell differentiation. Here, we report that the level of correlation between ploidy and cell volume is different in the outer and inner cell layers of leaves of Arabidopsis thaliana using a novel imaging technique. Although there is a well-known, strong correlation between ploidy and cell volume in pavement cells of the epidermis, this correlation was extremely weak in palisade mesophyll cells. Induction of epidermis cell identity based on the expression of the homeobox gene ATML1 in mesophyll cells enhanced the level of correlation between ploidy and cell volume to near that of wild-type epidermal cells. We therefore propose that the correlation between ploidy and cell volume is regulated by cell identity. PMID- 26903505 TI - Tumor protein Tctp regulates axon development in the embryonic visual system. AB - The transcript encoding translationally controlled tumor protein (Tctp), a molecule associated with aggressive breast cancers, was identified among the most abundant in genome-wide screens of axons, suggesting that Tctp is important in neurons. Here, we tested the role of Tctp in retinal axon development in Xenopus laevis We report that Tctp deficiency results in stunted and splayed retinotectal projections that fail to innervate the optic tectum at the normal developmental time owing to impaired axon extension. Tctp-deficient axons exhibit defects associated with mitochondrial dysfunction and we show that Tctp interacts in the axonal compartment with myeloid cell leukemia 1 (Mcl1), a pro-survival member of the Bcl2 family. Mcl1 knockdown gives rise to similar axon misprojection phenotypes, and we provide evidence that the anti-apoptotic activity of Tctp is necessary for the normal development of the retinotectal projection. These findings suggest that Tctp supports the development of the retinotectal projection via its regulation of pro-survival signalling and axonal mitochondrial homeostasis, and establish a novel and fundamental role for Tctp in vertebrate neural circuitry assembly. PMID- 26903509 TI - 60 YEARS OF POMC: Lipotropin and beta-endorphin: a perspective. AB - Many important fields of research had a humble origin. In the distant past, A J P Martin's discovery that amino acids could be separated by paper chromatography and Moore and Stein's use of columns for quantitative amino acid analysis provided the first steps towards the determination of structure in complex biologically active molecules. They opened the door to reveal the essential relationship that exists between structure and function. In molecular endocrinology, for example, striking advances have been made by chemists with their expertise in the identification of structure working with biologists who contributed valuable knowledge and experience. Advantage was gained from the convergence of different background, and it is notable that the whole is greater than the sum. In the determination of structure, it may be recalled that four of the world's great pioneers (Archibald Martin, Rodney Porter, Fred Sanger and Vincent du Vigneaud) were acknowledged for their fundamental contributions when individually they were awarded the Nobel Prize. They foresaw that the identification of structure would prove of outstanding importance in the future. Indeed, study of the structures of beta-endorphin and enkephalin and the different forms of opiate activity they engender has led to a transformation in our understanding of chemical transmission in the brain. PMID- 26903510 TI - 3,5-T2 alters murine genes relevant for xenobiotic, steroid, and thyroid hormone metabolism. AB - The endogenous thyroid hormone (TH) metabolite 3,5-diiodo-l-thyronine (3,5-T2) acts as a metabolically active substance affecting whole-body energy metabolism and hepatic lipid handling in a desirable manner. Considering possible adverse effects regarding thyromimetic action of 3,5-T2 treatment in rodents, the current literature remains largely controversial. To obtain further insights into molecular mechanisms and to identify novel target genes of 3,5-T2 in liver, we performed a microarray-based liver tissue transcriptome analysis of male lean and diet-induced obese euthyroid mice treated for 4 weeks with a dose of 2.5 ug/g bw 3,5-T2 Our results revealed that 3,5-T2 modulates the expression of genes encoding Phase I and Phase II enzymes as well as Phase III transporters, which play central roles in metabolism and detoxification of xenobiotics. Additionally, 3,5-T2 changes the expression of TH responsive genes, suggesting a thyromimetic action of 3,5-T2 in mouse liver. Interestingly, 3,5-T2 in obese but not in lean mice influences the expression of genes relevant for cholesterol and steroid biosynthesis, suggesting a novel role of 3,5-T2 in steroid metabolism of obese mice. We concluded that treatment with 3,5-T2 in lean and diet-induced obese male mice alters the expression of genes encoding hepatic xenobiotic-metabolizing enzymes that play a substantial role in catabolism and inactivation of xenobiotics and TH and are also involved in hepatic steroid and lipid metabolism. The administration of this high dose of 3,5-T2 might exert adverse hepatic effects. Accordingly, the conceivable use of 3,5-T2 as pharmacological hypolipidemic agent should be considered with caution. PMID- 26903511 TI - Autophagy protects osteoblasts from advanced glycation end products-induced apoptosis through intracellular reactive oxygen species. AB - Patients with type II diabetes are susceptible to fracture; however, these patients typically have normal bone mineral density. Thus, such fractures cannot be entirely explained by advanced glycation end products (AGEs)-induced osteoblast apoptosis. Autophagy is a molecular process allowing cells to degrade unnecessary or dysfunctional cellular organelles, and closely interacts with apoptosis. The aim of this study was to determine whether autophagy participated in the pathology of AGEs-treated osteoblasts, and the possible mechanism of such an involvement. Osteoblastic MC3T3-E1 cells were used. Autophagy was evaluated by detecting the level of LC3 via western blotting and immunofluorescence. p62/SQSTM1 expression was also assessed by western blotting. The autophagy inducer rapamycin (RA) and the autophagy inhibitor 3-methyladenine were used to determine whether autophagy has effect on AGEs-induced apoptosis. N Acetylcysteine (NAC), reactive oxygen species (ROS) inhibitor, was used to determine whether ROS and mitochondrial damage were involved in autophagy regulation. The results showed that the autophagy level was increased in MC3T3-E1 cells treated with AGEs, as represented by an increase in both the total LC3 level and the LC3II/LC3I ratio, as well as a decrease in p62/SQSTMI expression. Further inducing autophagy by RA attenuated AGEs-induced apoptosis. The antioxidant NAC suppresses AGEs-induced autophagy in osteoblastic MC3T3-E1 cells. These results demonstrate that autophagy participates in the pathology of AGEs treated osteoblasts, and may play a protective role in AGEs-induced apoptosis in osteoblastic MC3T3-E1 cells. ROS and mitochondrial damage are essential in upregulating AGEs-induced autophagy. PMID- 26903512 TI - The Proliferating Cell Nuclear Antigen (PCNA)-interacting Protein (PIP) Motif of DNA Polymerase eta Mediates Its Interaction with the C-terminal Domain of Rev1. AB - Y-family DNA polymerases, such as polymerase eta, polymerase iota, and polymerase kappa, catalyze the bypass of DNA damage during translesion synthesis. These enzymes are recruited to sites of DNA damage by interacting with the essential replication accessory protein proliferating cell nuclear antigen (PCNA) and the scaffold protein Rev1. In most Y-family polymerases, these interactions are mediated by one or more conserved PCNA-interacting protein (PIP) motifs that bind in a hydrophobic pocket on the front side of PCNA as well as by conserved Rev1 interacting region (RIR) motifs that bind in a hydrophobic pocket on the C terminal domain of Rev1. Yeast polymerase eta, a prototypical translesion synthesis polymerase, binds both PCNA and Rev1. It possesses a single PIP motif but not an RIR motif. Here we show that the PIP motif of yeast polymerase eta mediates its interactions both with PCNA and with Rev1. Moreover, the PIP motif of polymerase eta binds in the hydrophobic pocket on the Rev1 C-terminal domain. We also show that the RIR motif of human polymerase kappa and the PIP motif of yeast Msh6 bind both PCNA and Rev1. Overall, these findings demonstrate that PIP motifs and RIR motifs have overlapping specificities and can interact with both PCNA and Rev1 in structurally similar ways. These findings also suggest that PIP motifs are a more versatile protein interaction motif than previously believed. PMID- 26903513 TI - Major Histocompatibility Complex (MHC) Class I Processing of the NY-ESO-1 Antigen Is Regulated by Rpn10 and Rpn13 Proteins and Immunoproteasomes following Non lysine Ubiquitination. AB - The supply of MHC class I-restricted peptides is primarily ensured by the degradation of intracellular proteins via the ubiquitin-proteasome system. Depending on the target and the enzymes involved, ubiquitination is a process that may dramatically vary in terms of linkages, length, and attachment sites. Here we identified the unique lysine residue at position 124 of the NY-ESO-1 cancer/testis antigen as the acceptor site for the formation of canonical Lys-48 linkages. Interestingly, a lysine-less form of NY-ESO-1 was as efficient as its wild-type counterpart in supplying the HLA-A*0201-restricted NY-ESO-1157-165 antigenic peptide. In fact, we show that the regulation of NY-ESO-1 processing by the ubiquitin receptors Rpn10 and Rpn13 as a well as by the standard and immunoproteasome is governed by non-canonical ubiquitination on non-lysine sites. In summary, our data underscore the significance of atypical ubiquitination in the modulation of MHC class I antigen processing. PMID- 26903514 TI - Molecular Insights into Toluene Sensing in the TodS/TodT Signal Transduction System. AB - TodS is a sensor kinase that responds to various monoaromatic compounds, which either cause an agonistic or antagonistic effect on phosphorylation of its cognate response regulator TodT, and controls tod operon expression in Pseudomonas putida strains. We describe a molecular sensing mechanism of TodS that is activated in response to toluene. The crystal structures of the TodS Per Arnt-Sim (PAS) 1 sensor domain (residues 43-164) and its complex with toluene (agonist) or 1,2,4-trimethylbenzene (antagonist) show a typical beta2alpha3beta3 PAS fold structure (residues 45-149), forming a hydrophobic ligand-binding site. A signal transfer region (residues 150-163) located immediately after the canonical PAS fold may be intrinsically flexible and disordered in both apo-PAS1 and antagonist-bound forms and dramatically adapt an alpha-helix upon toluene binding. This structural change in the signal transfer region is proposed to result in signal transmission to activate the TodS/TodT two-component signal transduction system. Site-directed mutagenesis and beta-galactosidase assays using a P. putida reporter strain system verified the essential residues involved in ligand sensing and signal transfer and suggest that the Phe(46) residue acts as a ligand-specific switch. PMID- 26903515 TI - Functional Validation of ABCA3 as a Miltefosine Transporter in Human Macrophages: IMPACT ON INTRACELLULAR SURVIVAL OF LEISHMANIA (VIANNIA) PANAMENSIS. AB - Within its mammalian host, Leishmania resides and replicates as an intracellular parasite. The direct activity of antileishmanials must therefore depend on intracellular drug transport, metabolism, and accumulation within the host cell. In this study, we explored the role of human macrophage transporters in the intracellular accumulation and antileishmanial activity of miltefosine (MLF), the only oral drug available for the treatment of visceral and cutaneous leishmaniasis (CL). Membrane transporter gene expression in primary human macrophages infected in vitro with Leishmania Viannia panamensis and exposed to MLF showed modulation of ABC and solute liquid carrier transporters gene transcripts. Among these, ABCA3, a lipid transporter, was significantly induced after exposure to MLF, and this induction was confirmed in primary macrophages from CL patients. Functional validation of MLF as a substrate for ABCA3 was performed by shRNA gene knockdown (KD) in THP-1 monocytes. Intracellular accumulation of radiolabeled MLF was significantly higher in ABCA3(KD) macrophages. ABCA3(KD) resulted in increased cytotoxicity induced by MLF exposure. ABCA3 gene expression inversely correlated with intracellular MLF content in primary macrophages from CL patients. ABCA3(KD) reduced parasite survival during macrophage infection with an L. V. panamensis strain exhibiting low in vitro susceptibility to MLF. Confocal microscopy showed ABCA3 to be located in the cell membrane of resting macrophages and in intracellular compartments in L. V. panamensis-infected cells. These results provide evidence of ABCA3 as an MLF efflux transporter in human macrophages and support its role in the direct antileishmanial effect of this alkylphosphocholine drug. PMID- 26903516 TI - Insights into the Effects of Complement Factor H on the Assembly and Decay of the Alternative Pathway C3 Proconvertase and C3 Convertase. AB - The activated fragment of C3 (C3b) and factor B form the C3 proconvertase (C3bB), which is cleaved by factor D to C3 convertase (C3bBb). Older studies (Conrad, D. H., Carlo, J. R., and Ruddy, S. (1978)J. Exp. Med.147, 1792-1805; Pangburn, M. K., and Muller-Eberhard, H. J. (1978)Proc. Natl. Acad. Sci. U.S.A.75, 2416-2420; Kazatchkine, M. D., Fearon, D. T., and Austen, K. F. (1979)J. Immunol.122, 75-81) indicated that the complement alternative pathway regulator factor H (FH) competes with factor B for C3b binding; however, the capability of FH to prevent C3bB assembly has not been formally investigated. Moreover, in the few published studies FH did not favor C3bB dissociation. Whether FH may affect C3bBb formation from C3bB is unknown. We set up user-friendly assays based on combined microplate/Western blotting techniques that specifically detect either C3bB or C3bBb, with the aim of investigating the effect of FH on C3bB assembly and decay and C3bBb formation and decay. We document that FH does not affect C3bB assembly, indicating that FH does not efficiently compete with factor B for C3b binding. We also found that FH does not dissociate C3bB. FH showed a strong C3bBb decay accelerating activity, as reported previously, and also exerted an apparent inhibitory effect on C3bBb formation. The latter effect was not fully attributable to a rapid FH-mediated dissociation of C3bBb complexes, because blocking decay with properdin and C3 nephritic factor did not restore C3bBb formation. FH almost completely prevented release of the smaller cleavage subunit of FB (Ba), without modifying the amount of C3bB complexes, suggesting that FH inhibits the conversion of C3bB to C3bBb. Thus, the inhibitory effect of FH on C3bBb formation is likely the sum of inhibition of C3bB conversion to C3bBb and of C3bBb decay acceleration. Further studies are required to confirm these findings in physiological cell-based settings. PMID- 26903517 TI - RNF8 E3 Ubiquitin Ligase Stimulates Ubc13 E2 Conjugating Activity That Is Essential for DNA Double Strand Break Signaling and BRCA1 Tumor Suppressor Recruitment. AB - DNA double strand break (DSB) responses depend on the sequential actions of the E3 ubiquitin ligases RNF8 and RNF168 plus E2 ubiquitin-conjugating enzyme Ubc13 to specifically generate histone Lys-63-linked ubiquitin chains in DSB signaling. Here, we defined the activated RNF8-Ubc13~ubiquitin complex by x-ray crystallography and its functional solution conformations by x-ray scattering, as tested by separation-of-function mutations imaged in cells by immunofluorescence. The collective results show that the RING E3 RNF8 targets E2 Ubc13 to DSB sites and plays a critical role in damage signaling by stimulating polyubiquitination through modulating conformations of ubiquitin covalently linked to the Ubc13 active site. Structure-guided separation-of-function mutations show that the RNF8 E2 stimulating activity is essential for DSB signaling in mammalian cells and is necessary for downstream recruitment of 53BP1 and BRCA1. Chromatin-targeted RNF168 rescues 53BP1 recruitment involved in non-homologous end joining but not BRCA1 recruitment for homologous recombination. These findings suggest an allosteric approach to targeting the ubiquitin-docking cleft at the E2-E3 interface for possible interventions in cancer and chronic inflammation, and moreover, they establish an independent RNF8 role in BRCA1 recruitment. PMID- 26903518 TI - Up-regulation of Store-operated Ca2+ Entry and Nuclear Factor of Activated T Cells Promote the Acinar Phenotype of the Primary Human Salivary Gland Cells. AB - The signaling pathways involved in the generation and maintenance of exocrine gland acinar cells have not yet been established. Primary human salivary gland epithelial cells, derived from salivary gland biopsies, acquired an acinar-like phenotype when the [Ca(2+)] in the serum-free medium (keratinocyte growth medium, KGM) was increased from 0.05 mm (KGM-L) to 1.2 mm (KGM-H). Here we examined the mechanism underlying this Ca(2+)-dependent generation of the acinar cell phenotype. Compared with cells in KGM-L, those in KGM-H display enhancement of Orai1, STIM1, STIM2, and nuclear factor of activated T cells 1 (NFAT1) expression together with an increase in store-operated Ca(2+) entry (SOCE), SOCE-dependent nuclear translocation of pGFP-NFAT1, and NFAT-dependent but not NFkappaB dependent gene expression. Importantly, AQP5, an acinar-specific protein critical for function, is up-regulated in KGM-H via SOCE/NFAT-dependent gene expression. We identified critical NFAT binding motifs in the AQP5 promoter that are involved in Ca(2+)-dependent up-regulation of AQP5. These important findings reveal that the Ca(2+)-induced switch of salivary epithelial cells to an acinar-like phenotype involves remodeling of SOCE and NFAT signaling, which together control the expression of proteins critically relevant for acinar cell function. Our data provide a novel strategy for generating and maintaining acinar cells in culture. PMID- 26903519 TI - Use of Positron Emission Tomography to Detect Recurrence and Associations With Survival in Patients With Lung and Esophageal Cancers. AB - BACKGROUND: Positron emission tomography (PET) scans are often used in cancer patients for staging, restaging, and monitoring for treatment response. These scans are also often used to detect recurrence in asymptomatic patients, despite a lack of evidence demonstrating improved survival. We sought to evaluate utilization of PET for this purpose and relationships with survival for patients with lung and esophageal cancers. METHODS: Using national Surveillance, Epidemiology, and End Results (SEER) and Medicare-linked data, we identified incident patient cases from 2005 to 2009, with follow-up through 2011. We identified cohorts with primary lung (n = 97 152) and esophageal (n = 4446) cancers. Patient and tumor characteristics were used to calculate risk-adjusted two-year overall survival. Using Medicare claims, we examined PET utilization in person-years (to account for variable time in cohorts), excluding scans for staging and for follow-up of CT findings. We then stratified hospitals by quintiles of PET utilization for adjusted two-year survival analysis. All statistical tests were two-sided. RESULTS: There was statistically significant variation in utilization of PET. Lowest vs highest utilizing hospitals performed .05 (SD = 0.04) vs 0.70 (SD = 0.44) scans per person-year for lung cancer and 0.12 (SD = 0.06) vs 0.97 (SD = 0.29) scans per person-year for esophageal cancer. Despite this, for those undergoing PET, lowest vs highest utilizing hospitals had an adjusted two-year survival of 29.0% (SD = 12.1%) vs 28.8% (SD = 7.2%) for lung cancer (P = .66) and 28.4% (SD = 7.2%) vs 30.3% (SD = 5.9%) for esophageal cancer (P = .55). CONCLUSIONS: Despite statistically significant variation in use of PET to detect tumor recurrence, there was no association with improved two-year survival. These findings suggest possible overuse of PET for recurrence detection, which current Medicare policy would not appear to substantially affect. PMID- 26903520 TI - In vivo evaluation of retinal ganglion cells degeneration in eyes with branch retinal vein occlusion. AB - PURPOSE: To analyse the topographic changes in retinal ganglion cells (RGCs) in eyes with unilateral naive branch retinal vein occlusion (BRVO) in comparison to normal fellow eyes and to healthy control eyes. METHODS: We performed a retrospective analysis of 66 eyes (33 subjects) with naive unilateral BRVO who underwent spectral-domain optical coherence tomography using Cirrus HD-OCT. We also included 67 eyes of 48 age-matched healthy volunteers as control group. Average, minimum and sectoral macular ganglion cell-inner plexiform layer (GCIPL) thickness, macular retinal nerve fibre layer (RNFL) thickness and outer retinal thickness were collected. Comparison of the GCIPL, RNFL and outer retinal thicknesses among study eyes, normal fellow eyes and control groups was performed. RESULTS: The average and minimum macular GCIPL thicknesses were constantly and diffusely reduced in BRVO compared with normal fellow eyes and healthy controls (p<0.001 for each GCIPL sector). The average macular RNFL thickness was reduced in BRVO eyes compared with normal fellow eyes (p=0.01) and tended to be lower than controls (p=0.07). The minimum RNFL thickness in eyes with BRVO was significantly reduced when compared with fellow eyes (p<0.001) and control eyes (p<0.001). The average outer retina thickness was thicker in BRVO eyes compared with both fellow eyes (p<0.001) and controls (p<0.001). CONCLUSIONS: A significant reduction of the macular GCIPL and RNFL thicknesses was observed in eyes with BRVO. This finding is suggestive of RGCs degeneration; the neuroprotective effect of current therapeutic options might be an important consideration when evaluating treatment strategies and prognosticating visual outcome in BRVO eyes. PMID- 26903521 TI - The acceptability and visual impact of 0.01% atropine in a Caucasian population. AB - BACKGROUND: Myopia is a condition of enormous public health concern, affecting up to 2.5 billion people worldwide. The most effective treatment to prevent myopia progression is atropine but at the cost of accommodative paresis and mydriasis, necessitating the use of bifocal glasses. Low-dose atropine (0.01%) has been found to be almost as effective with significantly reduced side effects. Since there are well-recognised differences in the effect of atropine between heavily pigmented Asian eyes and Caucasian eyes, this study aimed to determine the acceptability and tolerability of 0.01% atropine (by measuring visual performance and quality of life) as a treatment for myopia control in a Caucasian population exhibiting light irides. METHODS: 14 university students aged 18-27 were recruited to the study. Participants received one drop of 0.01% atropine daily into each eye over 5 days. A range of physiological, functional and quality of life measures were assessed at baseline, day 3 and day 5. RESULTS: The effect of atropine was statistically significant for pupil size (p=0.04) and responsiveness (p<0.01). While amplitude of accommodation reduced, the change was not statistically significant. Visual acuity (distance and near) and reading speed were not adversely affected. While there was a slight increase in symptoms such as glare, overall there was no quality of life impact associated with the use of low-dose atropine. CONCLUSIONS: Overall, 0.01% of atropine was generally well tolerated bilaterally and no serious adverse effects were observed. Therefore this dose appears to provide a viable therapeutic option for myopia control among Caucasian eyes. PMID- 26903522 TI - Objective and subjective visual quality after implantation of all optic zone diffractive multifocal intraocular lenses: a prospective, case-control observational study. AB - BACKGROUND AND AIMS: To evaluate the objective and subjective optical quality of all optic zone diffractive multifocal intraocular lens (IOL). METHODS: Fifty patients (50 eyes) having phacoemulsification and IOL implantation surgery were enrolled. 25 patients were implanted with all optic zone diffractive multifocal IOL and 25 patients with monofocal IOL. Objective optical quality parameters under 4 mm pupil using Optical Quality Analysis System (OQAS), subjective visual acuity (VA) at 85 cd/m2 luminance and questionnaire concerning halo and visual function were assessed. RESULTS: The multifocal group gained similar objective optical outcomes, such as OQAS values at contrast 100%, 20%, 9%, modulation transfer function cut-off and Strehl ratio, as the monofocal group. Objective scatter index (OSI) was significantly better in the monofocal group. Distance corrected near VA, uncorrected near VA, distance corrected intermediate VA and uncorrected intermediate VA were significantly better in the multifocal group. The difference in uncorrected distance VA and best corrected distance VA between the monofocal and multifocal groups was not significant. Mild halos and glare were reported in both groups and a significant difference between the two groups was not observed; however, moderate glare and halos were reported only in the multifocal group (2/25). There was no significant difference between the two groups when visual function was compared. CONCLUSIONS: All optic zone diffractive multifocal IOLs provided almost the same objective optical quality as monofocal IOLs did under 4 mm pupil besides good all distance visual performance, but with greater OSI, indicating that implantation provides good optical quality in daytime but with more intraocular scatter light. TRIAL REGISTRATION NUMBER: NCT02234635, post-results. PMID- 26903523 TI - Cataract surgery in chronic Stevens-Johnson syndrome: aspects and outcomes. AB - AIM: To assess the outcome of cataract surgery in patients with chronic sequelae of Stevens-Johnson syndrome (SJS). METHODS: Setting: Tertiary eye care centre in South India. DESIGN: Retrospective, non-comparative, consecutive, interventional case series. Study period: March 2003 to May 2014. Of the 1662 consecutive patients with SJS, 32 patients (40 eyes) with chronic sequelae of SJS who underwent cataract surgery were included. The main outcome measures were best corrected visual acuity (BCVA) and ocular surface stabilisation. The visual acuity was expressed with reference to the logMAR. RESULTS: The study included 12 men (37.5%) and 20 women (62.5%). 8 patients (25%) had bilateral cataract surgeries. The median preoperative BCVA was 1.61 (IQR, 0.80 to 2.78) (only perception of light in three eyes). The median BCVA in the immediate postoperative period was 0.60 (IQR, 0.30 to 1.48) (perception of light in an eye) which was significantly different from the preoperative BCVA (p<0.0001). The median BCVA achieved was 0.30 (IQR, 0.00 to 0.80), suggesting further improvement. Median time taken to achieve this postoperatively was 1.5 months (IQR, 8 days to 3 months). The median BCVA during the last follow-up was 0.48 (IQR, 0.18 to 1.00). The preferred type of cataract surgery was phacoemulsification. Ocular surface condition remained stable in 35 eyes (87.5%). Ocular surface breakdown in four eyes (10%) was managed appropriately. CONCLUSION: Cataract surgery outcome can be visually rewarding in chronic sequelae of SJS provided ocular surface integrity is adequately maintained preoperatively and postoperatively. PMID- 26903524 TI - Long-term outcomes of intrastromal femtosecond laser presbyopia correction: 3 year results. AB - BACKGROUND/AIMS: To analyse visual outcomes and corneal changes 3 years after intrastromal femtosecond laser presbyopia treatment. METHODS: In a prospective, unicentric clinical trial, 25 presbyopic patients received INTRACOR treatment (Technolas femtosecond laser) on their non-dominant eye. Examinations were performed preoperatively as well as 1, 24 and 36 months postoperatively and included refraction, near, intermediate and distance visual acuity tests, reading speed, corneal topography, stray light measurement, endothelial cell count and slit-lamp examination. RESULTS: Comparison of preoperative versus 36 months postoperative values showed in median an improvement of uncorrected near visual acuity (UNVA) from 0.70 logMAR to 0.10 logMAR (p<0.001). Corrected distance visual acuity (CDVA) was reduced from -0.10 logMAR to 0.00 logMAR (p<0.001). The spherical equivalent preoperatively was 0.625 D and after an initial myopic shift after 1 month (0.125 D) and 24 months (0.25 D), the 36 months value (0.50 D) returned to resemble the preoperative value in statistical terms (p=0.123). A significant corneal steepening of 1.50 D in the treated area was measured. Pachymetry (thinnest point) revealed a statistically significant, but clinically insignificant corneal thickening from 535 to 549 um (p=0.033). Endothelial cell count did not change. 92.86% of patients felt comfortable with the surgery result. CONCLUSION: INTRACOR treatment after 36 months improved UNVA to varying degrees. The effect can be explained by a corneal steepening. An initial myopic shift was reversible. Reductions especially in CDVA have to be taken into account and therefore careful patient selection and information is obligatory. TRIAL REGISTRATION NUMBER: NCT01164358 and NCT01025050, Results. PMID- 26903526 TI - Doping in sport: consequences for health, clinicians and laboratories. PMID- 26903527 TI - Targeted Knockdown of GDCH in Rice Leads to a Photorespiratory-Deficient Phenotype Useful as a Building Block for C4 Rice. AB - The glycine decarboxylase complex (GDC) plays a critical role in the photorespiratory C2 cycle of C3 species by recovering carbon following the oxygenation reaction of ribulose-1,5-bisphosphate carboxylase/oxygenase. Loss of GDC from mesophyll cells (MCs) is considered a key early step in the evolution of C4 photosynthesis. To assess the impact of preferentially reducing GDC in rice MCs, we decreased the abundance of OsGDCH (Os10g37180) using an artificial microRNA (amiRNA) driven by a promoter that preferentially drives expression in MCs. GDC H- and P-proteins were undetectable in leaves of gdch lines. Plants exhibited a photorespiratory-deficient phenotype with stunted growth, accelerated leaf senescence, reduced chlorophyll, soluble protein and sugars, and increased glycine accumulation in leaves. Gas exchange measurements indicated an impaired ability to regenerate ribulose 1,5-bisphosphate in photorespiratory conditions. In addition, MCs of gdch lines exhibited a significant reduction in chloroplast area and coverage of the cell wall when grown in air, traits that occur during the later stages of C4 evolution. The presence of these two traits important for C4 photosynthesis and the non-lethal, down-regulation of the photorespiratory C2 cycle positively contribute to efforts to produce a C4 rice prototype. PMID- 26903528 TI - Oxidation of Cucurbitadienol Catalyzed by CYP87D18 in the Biosynthesis of Mogrosides from Siraitia grosvenorii. AB - Mogrosides, the principally bioactive compounds extracted from the fruits of Siraitia grosvenorii, are a group of glycosylated cucurbitane-type tetracyclic triterpenoid saponins that exhibit a wide range of notable biological activities and are commercially available worldwide as natural sweeteners. The biosynthesis of mogrosides involves initial cyclization of 2,3-oxidosqualene to the triterpenoid skeleton of cucurbitadienol, followed by a series of oxidation reactions catalyzed by Cyt P450s (P450s) and then glycosylation reactions catalyzed by UDP glycosyltransferases (UGTs). We previously reported the identification of a cucurbitadienol synthase (SgCbQ) and a mogrol C-3 hydroxyl glycosyltransferase (UGT74AC1). However, molecular characterization of further transformation of cucurbitadienol to mogrol by P450s remains unavailable. In this study, we report the successful identification of a multifunctional P450 (CYP87D18) as being involved in C-11 oxidation of cucurbitadienol. In vitro enzymatic activity assays showed that CYP87D18 catalyzed the oxidation of cucurbitadienol at C-11 to produce 11-oxo cucurbitadienol and 11-hydroxy cucurbitadienol. Furthermore, 11-oxo-24,25-epoxy cucurbitadienol as well as 11 oxo cucurbitadienol and 11-hydroxy cucurbitadienol were produced when CYP87D18 was co-expressed with SgCbQ in genetic yeast, and their structures were confirmed by liquid chromatography-solid-phase extraction-nuclear magnetic resonance-mass spectrometry coupling (LC-SPE-NMR-MS). Taken together, these results suggest a role for CYP87D18 as a multifunctional cucurbitadienol oxidase in the mogrosides pathway. PMID- 26903529 TI - Metabolic Network Constrains Gene Regulation of C4 Photosynthesis: The Case of Maize. AB - Engineering C3 plants to increase their efficiency of carbon fixation as well as of nitrogen and water use simultaneously may be facilitated by understanding the mechanisms that underpin the C4 syndrome. Existing experimental studies have indicated that the emergence of the C4 syndrome requires co-ordination between several levels of cellular organization, from gene regulation to metabolism, across two co-operating cell systems-mesophyll and bundle sheath cells. Yet, determining the extent to which the structure of the C4 plant metabolic network may constrain gene expression remains unclear, although it will provide an important consideration in engineering C4 photosynthesis in C3 plants. Here, we utilize flux coupling analysis with the second-generation maize metabolic models to investigate the correspondence between metabolic network structure and transcriptomic phenotypes along the maize leaf gradient. The examined scenarios with publically available data from independent experiments indicate that the transcriptomic programs of the two cell types are co-ordinated, quantitatively and qualitatively, due to the presence of coupled metabolic reactions in specific metabolic pathways. Taken together, our study demonstrates that precise quantitative coupling will have to be achieved in order to ensure a successfully engineered transition from C3 to C4 crops. PMID- 26903531 TI - Erratum to 'Heme oxygenase-1 suppresses a pro-inflammatory phenotype in monocytes and determines endothelial function and arterial hypertension in mice and humans'. PMID- 26903530 TI - Mitochondrial Alternative Pathway-Associated Photoprotection of Photosystem II is Related to the Photorespiratory Pathway. AB - Respiratory electron transport has two ubiquinol-oxidizing pathways, the cytochrome pathway (CP) and the alternative pathway (AP). The AP, which is catalyzed by the alternative oxidase (AOX), is energetically wasteful but may alleviate PSII photoinhibition under light conditions excessive for photosynthesis. However, its mechanism remains unknown. We used Arabidopsis aox1a mutants lacking AOX activity and studied the mutation's effects on photoinhibition by measuring the decrease in the maximum quantum yield of PSII (Fv/Fm) after high light exposure. Since the CP compensates for the lack of AOX, we monitored the extent of photoinhibition under conditions where CP activity is partially inhibited by antimycin A. When leaves were exposed to high light at 350 umol m-2 s-1, the decline in Fv/Fm was significantly faster in the aox1a mutants than in the wild type. However, under conditions where photorespiration was suppressed by high CO2 or low O2 levels, the decline in Fv/Fm was suppressed in the aox1a mutants, but not in the wild type, making the difference between the wild type and mutants small. Our results demonstrate that the lack of the AP causes an acceleration of PSII photoinhibition in relation to the photorespiratory pathway, suggesting that the AP can support the activity of the photorespiratory pathway under high light conditions. PMID- 26903532 TI - Prevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA): a 2 * 2 factorial, randomized, placebo-controlled, double-blind clinical trial of candesartan and metoprolol. AB - AIMS: Contemporary adjuvant treatment for early breast cancer is associated with improved survival but at the cost of increased risk of cardiotoxicity and cardiac dysfunction. We tested the hypothesis that concomitant therapy with the angiotensin receptor blocker candesartan or the beta-blocker metoprolol will alleviate the decline in left ventricular ejection fraction (LVEF) associated with adjuvant, anthracycline-containing regimens with or without trastuzumab and radiation. METHODS AND RESULTS: In a 2 * 2 factorial, randomized, placebo controlled, double-blind trial, we assigned 130 adult women with early breast cancer and no serious co-morbidity to the angiotensin receptor blocker candesartan cilexetil, the beta-blocker metoprolol succinate, or matching placebos in parallel with adjuvant anticancer therapy. The primary outcome measure was change in LVEF by cardiac magnetic resonance imaging. A priori, a change of 5 percentage points was considered clinically important. There was no interaction between candesartan and metoprolol treatments (P = 0.530). The overall decline in LVEF was 2.6 (95% CI 1.5, 3.8) percentage points in the placebo group and 0.8 (95% CI -0.4, 1.9) in the candesartan group in the intention-to-treat analysis (P-value for between-group difference: 0.026). No effect of metoprolol on the overall decline in LVEF was observed. CONCLUSION: In patients treated for early breast cancer with adjuvant anthracycline-containing regimens with or without trastuzumab and radiation, concomitant treatment with candesartan provides protection against early decline in global left ventricular function. PMID- 26903534 TI - Do You Want to Ditch Sodium? Meet Nitric Oxide Synthase 1beta at the Macula Densa. PMID- 26903536 TI - Characteristics of Oral Problems and Effects of Oral Care in Terminally Ill Patients With Cancer. AB - PURPOSE: Various distresses appear in the terminal stage of cancer. Oral problems including dry mouth, stomatitis and candidiasis are one of the important problems which should be resolved. The purpose of this study was to investigate oral problems in this stage and improvement of dry mouth by oral care. METHODS: The study subjects were consecutive terminally ill cancer patients admitted over the past 2 years. Patients were divided based on the status of oral food intake into good oral food intake group (>=30%) and poor oral food intake group. The following 3 items were retrospectively investigated: 1) The incidences of these oral problems, 2) Severity of dry mouth and complication with other oral problems, 3) Improvement of dry mouth using standard oral care by nursing staff and specialist oral care including dentists as needed. RESULTS: There were 115 and 158 patients in good and poor oral intake groups, respectively. 1) The incidences of dry mouth, stomatitis, and candidiasis were significantly higher in poor oral intake group ( p < 0.001). 2) Severe cases of dry mouth (Grade-2&3) were noted in 20.0% and 64.8% in good and poor oral intake groups, respectively ( p < 0.0001). Candidiasis complication rate was significantly higher in poor oral intake group ( p = 0.0002). 3) The rate of dry mouth improvement by oral care was 100% in Grade-1, 86% in Grade-2 and 81% in Grade-3. CONCLUSION: Oral problems occur in many of terminally ill cancer patients. Accurate diagnosis of oral problems and corresponding appropriate interventions are important for improving quality of end-of-life care. PMID- 26903537 TI - Rotating for elongation: Fat2 whips for the race. AB - Dynamic rearrangements of the actin cytoskeleton are crucial for cell shape and migration. In this issue, Squarr et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201508081) show that the cadherin superfamily protein Fat2 regulates actin-rich protrusions driving collective cell migration during Drosophila melanogaster egg morphogenesis through its interaction with the WAVE regulatory complex. PMID- 26903535 TI - Arabidopsis Small Rubber Particle Protein Homolog SRPs Play Dual Roles as Positive Factors for Tissue Growth and Development and in Drought Stress Responses. AB - Lipid droplets (LDs) act as repositories for fatty acids and sterols, which are used for various cellular processes such as energy production and membrane and hormone synthesis. LD-associated proteins play important roles in seed development and germination, but their functions in postgermination growth are not well understood. Arabidopsis (Arabidopsis thaliana) contains three SRP homologs (SRP1, SRP2, and SRP3) that share sequence identities with small rubber particle proteins of the rubber tree (Hevea brasiliensis). In this report, the possible cellular roles of SRPs in postgermination growth and the drought tolerance response were investigated. Arabidopsis SRPs appeared to be LD associated proteins and displayed polymerization properties in vivo and in vitro. SRP-overexpressing transgenic Arabidopsis plants (35S:SRP1, 35S:SRP2, and 35S:SRP3) exhibited higher vegetative and reproductive growth and markedly better tolerance to drought stress than wild-type Arabidopsis. In addition, constitutive over-expression of SRPs resulted in increased numbers of large LDs in postgermination seedlings. In contrast, single (srp1, 35S:SRP2-RNAi, and srp3) and triple (35S:SRP2-RNAi/srp1srp3) loss-of-function mutant lines exhibited the opposite phenotypes. Our results suggest that Arabidopsis SRPs play dual roles as positive factors in postgermination growth and the drought stress tolerance response. The possible relationships between LD-associated proteins and the drought stress response are discussed. PMID- 26903538 TI - Fat2 acts through the WAVE regulatory complex to drive collective cell migration during tissue rotation. AB - Directional cell movements during morphogenesis require the coordinated interplay between membrane receptors and the actin cytoskeleton. The WAVE regulatory complex (WRC) is a conserved actin regulator. Here, we found that the atypical cadherin Fat2 recruits the WRC to basal membranes of tricellular contacts where a new type of planar-polarized whip-like actin protrusion is formed. Loss of either Fat2 function or its interaction with the WRC disrupts tricellular protrusions and results in the formation of nonpolarized filopodia. We provide further evidence for a molecular network in which the receptor tyrosine phosphatase Dlar interacts with the WRC to couple the extracellular matrix, the membrane, and the actin cytoskeleton during egg elongation. Our data uncover a mechanism by which polarity information can be transduced from a membrane receptor to a key actin regulator to control collective follicle cell migration during egg elongation. 4D live imaging of rotating MCF10A mammary acini further suggests an evolutionary conserved mechanism driving rotational motions in epithelial morphogenesis. PMID- 26903539 TI - NBR1 enables autophagy-dependent focal adhesion turnover. AB - Autophagy is a catabolic pathway involving the sequestration of cellular contents into a double-membrane vesicle, the autophagosome. Although recent studies have demonstrated that autophagy supports cell migration, the underlying mechanisms remain unknown. Using live-cell imaging, we uncover that autophagy promotes optimal migratory rate and facilitates the dynamic assembly and disassembly of cell-matrix focal adhesions (FAs), which is essential for efficient motility. Additionally, our studies reveal that autophagosomes associate with FAs primarily during disassembly, suggesting autophagy locally facilitates the destabilization of cell-matrix contact sites. Furthermore, we identify the selective autophagy cargo receptor neighbor of BRCA1 (NBR1) as a key mediator of autophagy-dependent FA remodeling. NBR1 depletion impairs FA turnover and decreases targeting of autophagosomes to FAs, whereas ectopic expression of autophagy-competent, but not autophagy-defective, NBR1 enhances FA disassembly and reduces FA lifetime during migration. Our findings provide mechanistic insight into how autophagy promotes migration by revealing a requirement for NBR1-mediated selective autophagy in enabling FA disassembly in motile cells. PMID- 26903541 TI - Ordering Wisely: Engaging Faculty to Champion High-Value Care Initiatives. PMID- 26903540 TI - Drp1-dependent mitochondrial fission via MiD49/51 is essential for apoptotic cristae remodeling. AB - Mitochondrial fission facilitates cytochrome c release from the intracristae space into the cytoplasm during intrinsic apoptosis, although how the mitochondrial fission factor Drp1 and its mitochondrial receptors Mff, MiD49, and MiD51 are involved in this reaction remains elusive. Here, we analyzed the functional division of these receptors with their knockout (KO) cell lines. In marked contrast to Mff-KO cells, MiD49/MiD51-KO and Drp1-KO cells completely resisted cristae remodeling and cytochrome c release during apoptosis. This phenotype in MiD49/51-KO cells, but not Drp1-KO cells, was completely abolished by treatments disrupting cristae structure such as OPA1 depletion. Unexpectedly, OPA1 oligomers generally thought to resist cytochrome c release by stabilizing the cristae structure were similarly disassembled in Drp1-KO and MiD49/51-KO cells, indicating that disassembly of OPA1 oligomers is not directly linked to cristae remodeling for cytochrome c release. Together, these results indicate that Drp1-dependent mitochondrial fission through MiD49/MiD51 regulates cristae remodeling during intrinsic apoptosis. PMID- 26903542 TI - The Prognostic Value of Percentage Total Plaque Score Adjusted to Age. AB - BACKGROUND: Total plaque score (TPS) on coronary computed tomography angiography (CCTA) has been validated as a surrogate measure of coronary artery disease (CAD) burden and is prognostic. We propose a novel measure, percentage TPS adjusted to age (%TPS/age), that may reflect vascular age and potentially more rapidly progressive atherosclerosis and evaluate its potential prognostic value. METHODS: %TPS/age was calculated for consecutive patients prospectively enrolled into our institutional CCTA registry and evaluated for primary composite outcome of cardiac death, nonfatal myocardial infarction, and late revascularization. RESULTS: Of 1896 patients identified (mean age 57.7 +/- 11.4 years, 50.1% male, median follow-up 18.6 months [interquartile range: 15.3, 32.4]), 552 (29%) had %TPS/age = 0 (no atherosclerosis), with 1 (0.2%) primary outcome observed (annual event rate [AER] = 0.1%). Two events (0.4%, AER = 0.3%) were observed in %TPS/age < 0.314 category, 22 (5.0%, AER = 2.2%) in %TPS/age 0.314 to 0.699 category, and 54 (12.0%, AER = 5.7%) in %TPS/age >= 0.700 category. After adjusting for clinical predictors and obstructive CAD, higher %TPS/age category was associated with hazard ratio 1.95 (1.31-2.88, P < .001) for primary outcome on multivariable analysis, Harrell-C-Statistic 0.87 (confidence interval 95%: 0.84-0.90), and net reclassification improvement of 0.71 ( P < .001). CONCLUSION: %TPS/Age has incremental prognostic value to traditional risk factors and CCTA measures of CAD and improves evaluation of burden of coronary atherosclerosis and clinical risk. PMID- 26903543 TI - Combination of Levo-Tetrahydropalmatine and Low Dose Naltrexone: A Promising Treatment for Prevention of Cocaine Relapse. AB - Relapse to drug use is often cited as the major obstacle in overcoming a drug addiction. Whereas relapse can occur for a myriad of reasons, it is well established that complex neuroadaptations that occur over the course of addiction are major factors. Cocaine, as a potent dopamine transporter blocker, specifically induces alterations in the dopaminergic as well as other monoaminergic neurotransmissions, which lead to cocaine abuse and dependence. Evidence also suggests that adaptations in the endogenous opioids play important roles in pathophysiology of cocaine addiction. Following this evidence, we investigated a combination medication, levo-tetrahydropalmatine (l-THP) and low dose naltrexone (LDN), targeting primarily dopaminergic and endogenous opioid systems as a cocaine-relapse-prevention treatment. In the present study Wistar rats were used to assess the effects ofl-THP and LDN on cocaine self administration, drug-seeking behavior during cocaine reinstatement, spontaneous locomotion, and effects on the endogenous opioid system. We determined that the combination ofl-THP and LDN reduces drug-seeking behavior during reinstatement more potently thanl-THP alone. Additionally, the combination ofl-THP and LDN attenuates the sedative locomotor effect induced byl-THP. Furthermore, we revealed that treatment with the combination ofl-THP and LDN has an upregulatory effect on both plasmabeta-endorphin and hypothalamic POMC that was not observed inl-THP-treated groups. These results suggest that the combination ofl-THP and LDN has great potential as an effective and well-tolerated medication for cocaine relapse prevention. PMID- 26903545 TI - Telomerase gene therapy rescues telomere length, bone marrow aplasia, and survival in mice with aplastic anemia. AB - Aplastic anemia is a fatal bone marrow disorder characterized by peripheral pancytopenia and marrow hypoplasia. The disease can be hereditary or acquired and develops at any stage of life. A subgroup of the inherited form is caused by replicative impairment of hematopoietic stem and progenitor cells due to very short telomeres as a result of mutations in telomerase and other telomere components. Abnormal telomere shortening is also described in cases of acquired aplastic anemia, most likely secondary to increased turnover of bone marrow stem and progenitor cells. Here, we test the therapeutic efficacy of telomerase activation by using adeno-associated virus (AAV)9 gene therapy vectors carrying the telomerase Tert gene in 2 independent mouse models of aplastic anemia due to short telomeres (Trf1- and Tert-deficient mice). We find that a high dose of AAV9 Tert targets the bone marrow compartment, including hematopoietic stem cells. AAV9-Tert treatment after telomere attrition in bone marrow cells rescues aplastic anemia and mouse survival compared with mice treated with the empty vector. Improved survival is associated with a significant increase in telomere length in peripheral blood and bone marrow cells, as well as improved blood counts. These findings indicate that telomerase gene therapy represents a novel therapeutic strategy to treat aplastic anemia provoked or associated with short telomeres. PMID- 26903544 TI - Kruppeling erythropoiesis: an unexpected broad spectrum of human red blood cell disorders due to KLF1 variants. AB - Until recently our approach to analyzing human genetic diseases has been to accurately phenotype patients and sequence the genes known to be associated with those phenotypes; for example, in thalassemia, the globin loci are analyzed. Sequencing has become increasingly accessible, and thus a larger panel of genes can be analyzed and whole exome and/or whole genome sequencing can be used when no variants are found in the candidate genes. By using such approaches in patients with unexplained anemias, we have discovered that a broad range of hitherto unrelated human red cell disorders are caused by variants in KLF1, a master regulator of erythropoiesis, which were previously considered to be extremely rare causes of human genetic disease. PMID- 26903546 TI - Larger number of invariant natural killer T cells in PBSC allografts correlates with improved GVHD-free and progression-free survival. AB - We studied the impact of a set of immune cells contained within granulocyte colony-stimulating factor-mobilized peripheral blood stem cell grafts (naive and memory T-cell subsets, B cells, regulatory T cells, invariant natural killer T cells [iNKTs], NK cells, and dendritic cell subsets) in patients (n = 80) undergoing allogeneic stem cell transplantation (SCT), using the composite end point of graft-versus-host disease (GVHD)-free and progression-free survival (GPFS) as the primary end point. We observed that GPFS incidences in patients receiving iNKT doses above and below the median were 49% vs 22%, respectively (P= .007). In multivariate analysis, the iNKT dose was the only parameter with a significant impact on GPFS (hazard ratio = 0.48; 95% confidence interval, 0.27 0.85;P= .01). The incidences of severe grade III to IV acute GVHD and National Institutes of Health grade 2 to 3 chronic GVHD (12% and 16%, respectively) were low and associated with the use of antithymocyte globulin in 91% of patients. No difference in GVHD incidence was reported according to the iNKT dose. In conclusion, a higher dose of iNKTs within the graft is associated with an improved GPFS. These data may pave the way for prospective and active interventions aiming to manipulate the graft content to improve allo-SCT outcome. PMID- 26903547 TI - Exome sequencing reveals recurrent germ line variants in patients with familial Waldenstrom macroglobulinemia. AB - Familial aggregation of Waldenstrom macroglobulinemia (WM) cases, and the clustering of B-cell lymphoproliferative disorders among first-degree relatives of WM patients, has been reported. Nevertheless, the possible contribution of inherited susceptibility to familial WM remains unrevealed. We performed whole exome sequencing on germ line DNA obtained from 4 family members in which coinheritance for WM was documented in 3 of them, and screened additional independent 246 cases by using gene-specific mutation sequencing. Among the shared germ line variants, LAPTM5(c403t) and HCLS1(g496a) were the most recurrent, being present in 3/3 affected members of the index family, detected in 8% of the unrelated familial cases, and present in 0.5% of the nonfamilial cases and in <0.05 of a control population. LAPTM5 and HCLS1 appeared as relevant WM candidate genes that characterized familial WM individuals and were also functionally relevant to the tumor clone. These findings highlight potentially novel contributors for the genetic predisposition to familial WM and indicate that LAPTM5(c403t) and HCLS1(g496a) may represent predisposition alleles in patients with familial WM. PMID- 26903548 TI - Targeted gene editing restores regulated CD40L function in X-linked hyper-IgM syndrome. AB - Loss of CD40 ligand (CD40L) expression or function results in X-linked hyper immunoglobulin (Ig)M syndrome (X-HIGM), characterized by recurrent infections due to impaired immunoglobulin class-switching and somatic hypermutation. Previous attempts using retroviral gene transfer to correct murine CD40L expression restored immune function; however, treated mice developed lymphoproliferative disease, likely due to viral-promoter-dependent constitutive CD40L expression. These observations highlight the importance of preserving endogenous gene regulation in order to safely correct this disorder. Here, we report efficient, on-target, homology-directed repair (HDR) editing of the CD40LG locus in primary human T cells using a combination of a transcription activator-like effector nuclease-induced double-strand break and a donor template delivered by recombinant adeno-associated virus. HDR-mediated insertion of a coding sequence (green fluorescent protein or CD40L) upstream of the translation start site within exon 1 allowed transgene expression to be regulated by endogenous CD40LG promoter/enhancer elements. Additionally, inclusion of the CD40LG 3'-untranslated region in the transgene preserved posttranscriptional regulation. Expression kinetics of the transgene paralleled that of endogenous CD40L in unedited T cells, both at rest and in response to T-cell stimulation. The use of this method to edit X-HIGM patient T cells restored normal expression of CD40L and CD40 murine IgG Fc fusion protein (CD40-muIg) binding, and rescued IgG class switching of naive B cells in vitro. These results demonstrate the feasibility of engineered nuclease-directed gene repair to restore endogenously regulated CD40L, and the potential for its use in T-cell therapy for X-HIGM syndrome. PMID- 26903549 TI - Platelet microparticles inhibit IL-17 production by regulatory T cells through P selectin. AB - Self-tolerance and immune homeostasis are orchestrated by FOXP3(+)regulatory T cells (Tregs). Recent data have revealed that upon stimulation, Tregs may exhibit plasticity toward a proinflammatory phenotype, producing interleukin 17 (IL-17) and/or interferon gamma (IFN-gamma). Such deregulation of Tregs may contribute to the perpetuation of inflammatory processes, including graft-versus-host disease. Thus, it is important to identify immunomodulatory factors influencing Treg stability. Platelet-derived microparticles (PMPs) are involved in hemostasis and vascular health and have recently been shown to be intimately involved in (pathogenic) immune responses. Therefore, we investigated whether PMPs have the ability to affect Treg plasticity. PMPs were cocultured with healthy donor peripheral blood-derived Tregs that were stimulated with anti-CD3/CD28 monoclonal antibodies in the presence of IL-2, IL-15, and IL-1beta. PMPs prevented the differentiation of peripheral blood-derived Tregs into IL-17- and IFN-gamma producing cells, even in the presence of the IL-17-driving proinflammatory cytokine IL-1beta. The mechanism of action by which PMPs prevent Treg plasticity consisted of rapid and selective P-selectin-dependent binding of PMPs to a CCR6(+)HLA-DR(+)memory-like Treg subset and their ability to inhibit Treg proliferation, in part through CXCR3 engagement. The findings that ~8% of Tregs in the circulation of healthy individuals are CD41(+)P-selectin(+)and that distinct binding of patient plasma PMPs to Tregs was observed support in vivo relevance. These findings open the exciting possibility that PMPs actively regulate the immune response at sites of (vascular) inflammation, where they are known to accumulate and interact with leukocytes, consolidating the (vascular) healing process. PMID- 26903550 TI - What is the efficacy of switching to weekly pegvisomant in acromegaly patients well controlled on combination therapy? AB - CONTEXT: Although combination therapy of acromegaly with long-acting somatostatin analogs (LA-SSAs) and pegvisomant (PEGV) normalizes insulin-like growth factor-1 (IGF1) levels in the majority of patients, it requires long-term adherence. Switching from combination therapy to monotherapy with weekly PEGV could improve patients' comfort, but the efficacy is unknown. OBJECTIVE: To assess the efficacy of switching to PEGV monotherapy in patients well controlled on combination therapy of LA-SSAs and PEGV. DESIGN: Single-center, open-label observational pilot study. LA-SSA therapy was discontinued at baseline and all patients were switched to PEGV monotherapy for 12 months. If IGF1 levels exceeded 1.0 times upper limit of normal (ULN), PEGV dose was increased by 20 mg weekly. SUBJECTS AND METHODS: The study included 15 subjects (eight males), with a median age of 58 years (range 35-80) on combination therapy of high-dose LA-SSAs and weekly PEGV for >6 months, and IGF1 levels within the normal range. Treatment efficacy was assessed by measuring serum IGF1 levels. RESULTS: After 12 months of weekly PEGV monotherapy, serum IGF1 levels of 73% of the subjects remained controlled. In one patient, LA-SSA had to be restarted due to recurrence of headache. IGF1 levels increased from a baseline level of 0.62 * ULN (range 0.30-0.84) to 0.83 * ULN (0.30-1.75) after 12 months, while the median weekly PEGV dose increased from 60 (30-80) mg to 80 (50-120) mg. CONCLUSION: Our results suggest that switching from combination therapy of LA-SSAs and PEGV to PEGV monotherapy can be a viable treatment option for acromegaly patients without compromising efficacy. PMID- 26903551 TI - Institutional prevalence of malignancy of indeterminate thyroid cytology is necessary but insufficient to accurately interpret molecular marker tests. AB - OBJECTIVE: Several molecular marker tests are available to refine the diagnosis of thyroid nodules. Knowing the true prevalence of malignancy (PoM) within each cytological category is considered necessary to select the most appropriate test and to interpret results accurately. We describe our institutional PoM among cytological categories and report our experience with molecular markers. DESIGN: Single-center retrospective study. METHODS: We calculated the institutional PoM for each category of the Bethesda system (Bethesda) on all thyroid nodules with cytological evaluation from October 2008 to May 2014. We estimated the predictive values for Afirma, miRInform, and ThyroSeq v2, based on published sensitivity and specificity. Finally, we assessed our own experience with miRInform. RESULTS: The PoMs for Bethesda III and IV categories were 21 and 28%, respectively. ThyroSeq v2 achieves the highest theoretical negative and positive predictive values (NPV and PPV) in Bethesda III (98 and 75%) and Bethesda IV categories (96 and 83%). At our institution, miRInform detected a mutation in 16% of 109 indeterminate nodules tested, all in Bethesda IV specimens. Histology was available in 56 (51%) nodules. The observed sensitivity and specificity in Bethesda IV specimens were 63 and 86%, yielding an NPV and a PPV of 75 and 77%, respectively. CONCLUSIONS: For our current Bethesda III and IV PoM, the actual performance of miRInform was worse than expected. Theoretically ThyroSeq v2 should have the best performance, but it could be affected in the same way as miRInform, given the similarities between the tests. Assessing the institutional performance of each test is necessary along with PoM individualization. PMID- 26903552 TI - Is safety of childhood growth hormone therapy related to dose? Data from a large observational study. AB - OBJECTIVE: Concerns have been raised of increased mortality risk in adulthood in certain patients who received growth hormone treatment during childhood. This study evaluated the safety of growth hormone treatment in childhood in everyday practice. DESIGN: NordiNet((r)) International Outcome Study (IOS) is a noninterventional, observational study evaluating safety and effectiveness of Norditropin((r)) (somatropin; Novo Nordisk A/S, Bagsvaerd, Denmark). METHODS: Long-term safety data (1998-2013) were collected on 13 834 growth hormone treated pediatric patients with short stature. Incidence rates (IRs) of adverse events (AEs) defined as adverse drug reactions (ADRs), serious ADRs (SADRs), and serious AEs (SAEs) were calculated by mortality risk group (low/intermediate/high). The effect of growth hormone dose on IRs and the occurrence of cerebrovascular AEs were investigated by the risk group. RESULTS: We found that 61.0% of patients were classified as low-risk, 33.9% intermediate-risk, and 5.1% high-risk. Three hundred and two AEs were reported in 261 (1.9%) patients during a mean (s.d.) treatment duration of 3.9 (2.8) years. IRs were significantly higher in the high- vs the low-risk group (high risk vs low risk-ADR: 9.11 vs 3.14; SAE: 13.66 vs 1.85; SADR: 4.97 vs 0.73 events/1000 patient-years of exposure; P < 0.0001 for all). Except for SAEs in the intermediate-risk group (P = 0.0486) in which an inverse relationship was observed, no association between IRs and growth hormone dose was found. No cerebrovascular events were reported. CONCLUSIONS: We conclude that safety data from NordiNet((r)) IOS do not reveal any new safety signals and confirm a favorable overall safety profile in accordance with other pediatric observational studies. No association between growth hormone dose and the incidence of AEs during growth hormone treatment in childhood was found. PMID- 26903553 TI - Growth patterns of patients with Noonan syndrome: correlation with age and genotype. AB - BACKGROUND: Growth patterns of patients with Noonan syndrome (NS) were established before the involved genes were identified. OBJECTIVE: The goal of this study was to compare growth parameters according to genotype in patients with NS. SUBJECTS AND METHODS: The study population included 420 patients (176 females and 244 males) harboring mutations in the PTPN11, SOS1, RAF1, or KRAS genes. NS-associated PTPN11 mutations (NS-PTPN11) and NS with multiple lentigines associated PTPN11 mutations (NSML-PTPN11) were distinguished. Birth measures and height and body mass index (BMI) measures at 2, 5, 10 years, and adulthood were compared with the general population and between genotypes. RESULTS: Patients with NS were shorter at birth (mean birth length standard deviation score (SDS): 1.0 +/- 1.4; P < 0.001) and throughout childhood than the healthy population, with height SDS being -2.1 +/- 1.3 at 2 years, and -2.1 +/- 1.2 at 5 and 10 years and adulthood (P < 0.001). At birth, patients with NS-PTPN11 were significantly shorter and thinner than patients with NSML-PTPN11, SOS1, or KRAS. Growth retardation was significantly less severe and less frequent at 2 years in patients with NSML-PTPN11 and SOS1 than in patients with NS-PTPN11 (P < 0.001 and P = 0.002 respectively). Patients with NS had lower BMI at 10 years (P < 0.001). No difference between genotypes was demonstrated. CONCLUSION: Determining the growth patterns of patients with NS according to genotype should better inform clinicians about the natural course of growth in NS so that they can optimize the follow-up and management of these patients. PMID- 26903554 TI - The Pediatric Infectious Diseases Developmental Screening Test 2.0. AB - Wholesale revision of the Pediatric Infectious Diseases Developmental Screening Test (PIDDST) was imperative, given the sea change that has occurred in academic medicine and subspecialty practice in the last two decades. The PIDDST 2.0 tracks expected milestones along the continuum from fellow to full professor in today's complex health care environment. Effective use of this instrument in training programs and pediatric departments could help shape the future of the field. PMID- 26903555 TI - Pharmacodynamically Guided Levofloxacin Dosing for Pediatric Community-Acquired Pneumonia. AB - Background.: Oral levofloxacin is recommended as a preferred treatment for infection with Streptococcus pneumoniae with a penicillin minimum inhibitory concentration (MIC) of >=4 ug/mL and as an alternative for infection with S pneumoniae with a penicillin MIC of <=2 ug/mL. To investigate the current dosing recommendations and create a pharmacodynamically guided regimen, a Monte Carlo simulation was performed. Methods.: The simulation included a previously published 1-compartment model, and incorporated a formula that takes into account age-appropriate weights for hospitalized patients. Three different dosing regimens, including community-acquired pneumonia guideline dosing, inhalational anthrax dosing, and a pharmacodynamically guided regimen, were assessed. The probability of target attainment was described as the proportion of patients who achieve an unbound-drug area under the concentration-time curve over 24 hours divided by the MIC above 33.7 ug/mL per hour. Microbiologic data from 2 stand alone pediatric tertiary care centers were included. Results.: Guideline recommended doses of levofloxacin seem to produce suboptimal exposure in patients aged 5-14 years for pneumococci with an MIC of 1 ug/mL. Anthrax dosing was suboptimal in patients aged <5 years and in those aged >15 years. The pharmacodynamically guided regimen maintained a probability of target attainment of >90% for all age groups without producing peak concentrations higher than those previously described. None of the regimens attained the pharmacodynamic targets for a levofloxacin MIC of 2 ug/mL. Conclusions.: Current dosing recommendations were found to be suboptimal for specific age groups. A pharmacodynamically guided levofloxacin dosing regimen was determined, but it will need to be studied clinically for safety and tolerability. PMID- 26903556 TI - Risk of vitamin D deficiency rises with breast feeding after age 1, study shows. PMID- 26903557 TI - Abdominal pain and hematuria: duodenal perforation from ingested foreign body causing ureteral obstruction and hydronephrosis. AB - Foreign body (FB) ingestion is a relatively common reason for visits to the emergency room. If the FB is symptomatic or damaging to the patient, either endoscopic or surgical intervention should ensue. We present a case of abdominal pain and hematuria beginning ~24 h after an incidental FB ingestion. Initial CT imaging defined a linear opacity perforating through the posterior duodenal wall abutting the ureter causing inflammation and hydronephrosis. After two unsuccessful endoscopic attempts at retrieval, we were able to identify the object with the aid of intraoperative fluoroscopy and surgically remove the FB. The patient recovered uneventfully and was discharged home. Posterior duodenal perforation by an FB may not manifest with obvious localized or systemic symptoms unless the perforation involves surrounding structures such as the aorta, vena cava or ureter. In such cases, surgical intervention is required for FB removal. PMID- 26903558 TI - Analysis of Subcellular RNA Fractions Revealed a Transcription-Independent Effect of Tumor Necrosis Factor Alpha on Splicing, Mediated by Spt5. AB - The proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha) modulates the expression of many genes, primarily through activation of NF-kappaB. Here, we examined the global effects of the elongation factor Spt5 on nascent and mature mRNAs of TNF-alpha-induced cells using chromatin and cytosolic subcellular fractions. We identified several classes of TNF-alpha-induced genes controlled at the level of transcription, splicing, and chromatin retention. Spt5 was found to facilitate splicing and chromatin release in genes displaying high induction rates. Further analysis revealed striking effects of TNF-alpha on the splicing of 25% of expressed genes; the vast majority were not transcriptionally induced. Splicing enhancement of noninduced genes by TNF-alpha was transient and independent of NF-kappaB. Investigating the underlying basis, we found that Spt5 is required for the splicing facilitation of the noninduced genes. In line with this, Spt5 interacts with Sm core protein splicing factors. Furthermore, following TNF-alpha treatment, levels of RNA polymerase II (Pol II) but not Spt5 are reduced from the splicing-induced genes, suggesting that these genes become enriched with a Pol II-Spt5 form. Our findings revealed the Pol II-Spt5 complex as a highly competent coordinator of cotranscriptional splicing. PMID- 26903559 TI - Adenosine to protect the myocardium. PMID- 26903561 TI - Application of Raman Spectroscopy and Infrared Spectroscopy in the Identification of Breast Cancer. AB - Raman spectroscopy and infrared (IR) spectroscopy are both techniques that allow for the investigation of vibrating chemical particles. These techniques provide information not only about chemical particles through the identification of functional groups and spectral analysis of so-called "fingerprints", these methods allow for the qualitative and quantitative analyses of chemical substances in the sample. Both of these spectral techniques are frequently being used in biology and medicine in diagnosing illnesses and monitoring methods of therapy. The type of breast cancer found in woman is often a malignant tumor, causing 1.38 million new cases of breast cancer and 458 000 deaths in the world in 2013. The most important risk factors for breast cancer development are: sex, age, family history, specific benign breast conditions in the breast, ionizing radiation, and lifestyle. The main purpose of breast cancer screening tests is to establish early diagnostics and to apply proper treatment. Diagnoses of breast cancer are based on: (1) physical techniques (e.g., ultrasonography, mammography, elastography, magnetic resonance, positron emission tomography [PET]); (2) histopathological techniques; (3) biological techniques; and (4) optical techniques (e.g., photo acoustic imaging, fluorescence tomography). However, none of these techniques provides unique or especially revealing answers. The aim of our study is comparative spectroscopic measurements on patients with the following: normal non-cancerous breast tissue; breast cancer tissues before chemotherapy; breast cancer tissues after chemotherapy; and normal breast tissues received around the cancerous breast region. Spectra collected from breast cancer patients shows changes in amounts of carotenoids and fats. We also observed changes in carbohydrate and protein levels (e.g., lack of amino acids, changes in the concentration of amino acids, structural changes) in comparison with normal breast tissues. This fact verifies that Raman spectroscopy and IR spectroscopy are very useful diagnostic tools that will shed new light in understanding the etiology of breast cancer. PMID- 26903562 TI - Investigating the Distribution of Chemical Forms of Sulfur in Prostate Cancer Tissue Using X-ray Absorption Spectroscopy. AB - The use of synchrotron radiation may shed more light on the study of prostate cancer, one of the leading diseases among men. In the presented study the microbeam setup at the PSI Swiss Light Source combined with fluorescence detected X-ray absorption spectroscopy (XAS) was applied to determine two-dimensional (2D) imaging of distributions of various chemical sulfur forms in prostate cancer tissue sections, since sulfur is considered important and essential in cancer progression. The research focused on prostate tissues obtained during routine prostatectomies on patients suffering from prostate cancer.Our previous studies using MU-XAS point measurements on prostate cancer cell lines showed the differences in fractions of various forms of sulfur between cancerous and non cancerous cells. Therefore, in this experiment the chosen areas of prostate cancer tissues were scanned to get the full picture of the chemical composition of tissue, which is highly heterogeneous. The incident X-ray beams of energies tuned to spectroscopic features of the near-edge region of sulfur K-edge absorption spectra were used to provide contrast between chemical species presented in the tissue. Next, the relative content of the three main sulfur forms, found in biological systems, was calculated and the results are presented in a form of 2D color maps. These maps are correlated with the microscopic histological image of the scanned area.The main findings show that sulfur occurs in prostate tissue mainly in reduced form. The oxidized form of sulfur is present mostly in prostatic stroma, while sulfur in intermediate oxidation state is present in trace amount. PMID- 26903563 TI - Traceable Quantitative Raman Microscopy and X-ray Fluorescence Analysis as Nondestructive Methods for the Characterization of Cu(In,Ga)Se2 Absorber Films. AB - The traceability of measured quantities is an essential condition when linking process control parameters to guaranteed physical properties of a product. Using Raman spectroscopy as an analytical tool for monitoring the production of Cu(In1 xGax)Se2 thin-film solar cells, proper calibration with regard to chemical composition and lateral dimensions is a key prerequisite. This study shows how the multiple requirements of calibration in Raman microscopy might be addressed. The surface elemental composition as well as the integral elemental composition of the samples is traced back by reference-free X-ray fluorescence analysis. Reference Raman spectra are then generated for the relevant Cu(In1-xGax)Se2 related compounds. The lateral dimensions are calibrated with the help of a novel dimensional standard whose regular structures have been traced back to the International System of Units by metrological scanning force microscopy. On this basis, an approach for the quantitative determination of surface coverage values from lateral Raman mappings is developed together with a complete uncertainty budget. Raman and X-ray spectrometry have here been proven as complementary nondestructive methods combining surface sensitivity and in-depth information on elemental and species distribution for the reliable quality control of Cu(In1 xGax)Se2 absorbers and Cu(In1-xGax)3Se5 surface layer formation. PMID- 26903564 TI - In Situ Confocal Raman Microscopy of Hydrated Early Stages of Bacterial Biofilm Formation on Various Surfaces in a Flow Cell. AB - Bacterial biofilms are precursors to biofouling by other microorganisms. Understanding their initiation may allow us to design better ways to inhibit them, and thus to inhibit subsequent biofouling. In this study, the ability of confocal Raman microscopy to follow the initiation of biofouling by a marine bacterium, Pseudoalteromonas sp. NCIMB 2021 (NCIMB 2021), in a flow cell, using optical and confocal Raman microscopy, was investigated. The base of the flow cell comprised a cover glass. The cell was inoculated and the bacteria attached to, and grew on, the cover glass. Bright field images and Raman spectra were collected directly from the hydrated biofilms over several days. Although macroscopically the laser had no effect on the biofilm, within the first 24 h cells migrated away from the position of the laser beam. In the absence of flow, a buildup of extracellular substances occurred at the base of the biofilm. When different coatings were applied to cover glasses before they were assembled into the flow cells, the growth rate, structure, and composition of the resulting biofilm was affected. In particular, the ratio of Resonance Raman peaks from cytochrome c (CC) in the extracellular polymeric substances, to the Raman phenylalanine (Phe) peak from protein in the bacteria, depended on both the nature of the surface and the age of the biofilm. The ratios were highest for 24 h colonies on a hydrophobic surface. Absorption of a surfactant with an ethyleneoxy chain into the hydrophobic coating created a surface similar to that given with a simple PEG coating, where bacteria grew in colonies away from the surface rather than along the surface, and CC:Phe ratios were initially low but increased at least fivefold in the first 48 h. PMID- 26903565 TI - Determination of the Dipole Geometry of Fluorescent Nanoparticles Using Polarized Excitation and Emission Analysis. AB - We demonstrate that the geometries of the absorption dipole MUab and emission dipole MUem of nano-emitters such as quantum dots can be determined simultaneously by far-field polarimetry. The method involves plotting the emission polarization ratio against the absorption polarization ratio of single nano-emitters. Using Monte Carlo simulation, we show that these plots depend sensitively on the aspect ratio of the dipole shape. For example, the so-called 3D-2D dipole combination, that is, MUab of radius ratio 1:1:1 and MUem of ratio 1:1:0, would give rise to a vertical line plot. Polarization ratios of commercial cadmium selenide/zinc sulfide (CdSe/ZnS) quantum dots are measured and plotted. The empirical data points are best-fitted to yield MUab of radius ratio 1:1:0.28 and MUem of ratio 1:1:0. PMID- 26903566 TI - Selective and Sensitive Chemiluminescence Determination of MCPB: Flow Injection and Liquid Chromatography. AB - Two new chemiluminescence (CL) methods are described for the determination of the herbicide 4-(4-chloro-o-tolyloxy) butyric acid (MCPB). First, a flow injection chemiluminescence (FI-CL) method is proposed. In this method, MCPB is photodegraded with an ultraviolet (UV) lamp and the photoproducts formed provide a great CL signal when they react with ferricyanide in basic medium. Second, a high-performance liquid chromatography chemiluminescence (HPLC-CL) method is proposed. In this method, before the photodegradation and CL reaction, the MCPB and other phenoxyacid herbicides are separated in a C18 column. The experimental conditions for the FI-CL and HPLC-CL methods are optimized. Both methods present good sensitivity, the detection limits being 0.12 ug L(-1) and 0.1 ug L(-1) (for FI-CL and HPLC-CL, respectively) when solid phase extraction (SPE) is applied. Intra- and interday relative standard deviations are below 9.9%. The methods have been satisfactorily applied to the analysis of natural water samples. FI-CL method can be employed for the determination of MCPB in simple water samples and for the screening of complex water samples in a fast, economic, and simple way. The HPLC-CL method is more selective, and allows samples that have not been resolved with the FI-CL method to be solved. PMID- 26903567 TI - Random Forest (RF) Wrappers for Waveband Selection and Classification of Hyperspectral Data. AB - Hyperspectral data collected using a field spectroradiometer was used to model asymptomatic stress in Pinus radiata and Pinus patula seedlings infected with the pathogen Fusarium circinatum. Spectral data were analyzed using the random forest algorithm. To improve the classification accuracy of the model, subsets of wavebands were selected using three feature selection algorithms: (1) Boruta; (2) recursive feature elimination (RFE); and (3) area under the receiver operating characteristic curve of the random forest (AUC-RF). Results highlighted the robustness of the above feature selection methods when used in conjunction with the random forest algorithm for analyzing hyperspectral data. Overall, the Boruta feature selection algorithm provided the best results. When discriminating F. circinatum stress in Pinus radiata seedlings, Boruta selected wavebands (n = 69) yielded the best overall classification accuracies (training error of 17.00%, independent test error of 17.00% and an AUC value of 0.91). Classification results were, however, significantly lower for P. patula seedlings, with a training error of 24.00%, independent test error of 38.00%, and an AUC value of 0.65. A hybrid selection method that utilizes combinations of wavebands selected from the three feature selection algorithms was also tested. The hybrid method showed an improvement in classification accuracies for P. patula, and no improvement for P. radiata. The results of this study provide impetus towards implementing a hyperspectral framework for detecting stress within nursery environments. PMID- 26903568 TI - In Situ Raman Spectroscopic Study of Barite as a Pressure Gauge Using a Hydrothermal Diamond Anvil Cell. AB - In situ Raman measurements of barite were performed at temperatures in the range of 298-673 K and pressures in the range of 105-1217 MPa using a hydrothermal diamond anvil cell combined with laser Raman spectroscopy. The Raman frequency and the full width at half maximum (FWHM) of the most intense nu1 Raman peak for barite as a function of pressure and temperature were obtained. In the experimental P-T ranges, the nu1Raman band systematically shifted toward low wavenumbers with increasing pressure and temperature. The positive pressure dependence of nu1Raman frequency indicates stress-induced shortening of the S-O bond, whereas the negative temperature dependence shows temperature-induced expansion of the S-O bond. In contrast, the observed nu1Raman band became broadened, which should be attributed to the reduced ordering of molecular structure. Based on the obtained data, the established relationships among the Raman shift or the FWHM, pressure and temperature can be used to obtain good estimates of the internal pressure in natural barite-bearing fluid inclusions or hydrothermal diamond anvil cell. This is a sensitive and reliable approach to the accurate determination of geological pressure. PMID- 26903569 TI - A Turn-On Resonance Raman Scattering (BCS/Cu+) Sensor for Quantitative Determination of Proteins. AB - In this study, a new method for the quantitative evaluation of proteins is developed using competitive resonance Raman spectroscopy. A chelation reaction between bathocuproine disulfonate (BCS) and Cu(+) which is reduced by proteins in an alkaline environment, is utilized to create a BCS-Cu(+) complex that has strong resonance Raman activity. As a result, the method presented here enables protein detection over a much wider concentration range than conventional methods. Furthermore, the resonance Raman-based method can provide an improved lower limit of detection (500 pg/mL) compared to that obtained by colorimetric and ultraviolet- (UV-) based methods. Additionally, protein-to-protein variation can be determined using a standard curve created from known concentrations of bovine serum albumin (BSA), and excellent protein recovery is observed. More importantly, the proposed method was employing to the real sample (fetal bovine serum [FBS]). Based on the calibration curve from this method, it is extremely accurate for the determination of total protein concentrations in FBS. Results of this study demonstrate that the proposed method provides a novel and highly sensitive protocol for reagent-based protein assays. PMID- 26903570 TI - Possible Influences on the Interpretation of Functional Domain (FD) Near-Infrared Spectroscopy (NIRS): An Explorative Study. AB - The influence of subcutaneous adipose tissue (ATT) and oxygen (O2) delivery has been poorly defined in frequency domain (FD) near-infrared spectroscopy (NIRS). Therefore, the aim of this study was to investigate the possible influence of these variables on all FD NIRS responses using a reliable protocol. Moreover, these influences were also investigated when using relative oxy- and deoxyhemoglobin and -myoglobin (oxy[Hb + Mb] and deoxy[Hb + Mb]) values (in %). A regression analysis was carried out for ATT and maximal-minimum oxy[Hb + Mb], deoxy[Hb + Mb], oxygen saturation (SmO2), and total hemoglobin (totHb) amplitudes during an incremental cyclic contraction protocol (ICCP) in a group of 45 participants. Moreover, the same analysis was carried out between subcutaneous ATT and the relative oxy- and deoxy[Hb + Mb] values (in %). In the second part of this study, a regression analysis was performed for peak forearm blood flow (FBF) during ICCP and the absolute and relative NIRS values in a group of 37 participants. Significant exponential correlation coefficients were found between ATT and deoxy[Hb + Mb] (r = 0.53; P < 0.001), oxy[Hb + Mb] (r = 0.57; P < 0.001), and SmO2 amplitudes (r = 0.57; P < 0.001). No significant relations were found between ATT and relative oxy[Hb + Mb] (r = 0.37; P = 0.07) and deoxy[Hb + Mb] (r = 0.09; P = 0.82). Significant positive correlation coefficients were found between force at exhaustion and maximal FBF (r = 0.66; P < 0.001), maximal differences in deoxy[Hb + Mb] (r = 0.353; P = 0.032) and totHb (r = 0.512; P = 0.002) while no significant correlation coefficients were found between these maximal force values and maximal differences in oxy[Hb + Mb] (r = -0.267; P = 0.111) and SmO2 (r = -0.267; P = 0.111). Significant linear correlation coefficients were found between FBF and deoxy[Hb + Mb] (r = 0.51; P = 0.001), oxy[Hb + Mb] (r = -0.50; P = 0.001), SmO2 (r = -0.54; P = 0.001), and totHb amplitude (r = 0.61; P < 0.001). No significant correlations were found when using relative oxy[Hb + Mb] (r = -0.01; P = 0.957) and deoxy[Hb + Mb] (r = -0.02; P = 0.895). Based on these findings, caution is advised when using NIRS values, as subcutaneous ATT and O2 delivery significantly influence NIRS measurements. To eliminate these influences, use of relative deoxy[Hb + Mb] is advised, especially in clinical settings or in people with a higher subcutaneous ATT layer. PMID- 26903571 TI - Should the Benefit of Adjuvant Chemotherapy in Colon Cancer Be Re-Evaluated? PMID- 26903572 TI - Loss of Muscle Mass During Chemotherapy Is Predictive for Poor Survival of Patients With Metastatic Colorectal Cancer. AB - PURPOSE: Low muscle mass is present in approximately 40% of patients with metastatic colorectal cancer (mCRC) and may be associated with poor outcome. We studied change in skeletal muscle during palliative chemotherapy in patients with mCRC and its association with treatment modifications and overall survival. PATIENTS AND METHODS: In 67 patients with mCRC (mean age +/- standard deviation, 66.4 +/- 10.6 years; 63% male), muscle area (square centimeters) was assessed using computed tomography scans of the third lumbar vertebra before and during palliative chemotherapy. Treatment modifications resulting from toxicity were evaluated, including delay, dose reduction, or termination of chemotherapy. Multiple regression analyses were performed for the association between change in muscle area and treatment modification and secondly overall survival. RESULTS: Muscle area of patients with mCRC decreased significantly during 3 months of chemotherapy by 6.1% (95% CI, -8.4 to -3.8; P < .001). Change in muscle area was not associated with treatment modifications. However, patients with muscle loss during treatment of 9% or more (lowest tertile) had significantly lower survival rates than patients with muscle loss of less than 9% (at 6 months, 33% v 69% of patients alive; at 1 year, 17% v 49% of patients alive; log-rank P = .001). Muscle loss of 9% or more remained independently associated with survival when adjusted for sex, age, baseline lactate dehydrogenase concentration, comorbidity, mono-organ or multiorgan metastases, treatment line, and tumor progression at first evaluation by computed tomography scan (hazard ratio, 4.47; 95% CI, 2.21 to 9.05; P < .001). CONCLUSION: Muscle area decreased significantly during chemotherapy and was independently associated with survival in patients with mCRC. Further clinical evaluation is required to determine whether nutritional interventions and exercise training may preserve muscle area and thereby improve outcome. PMID- 26903573 TI - Compartmentalizing Cancer. PMID- 26903574 TI - Depressive Symptoms in Patients Scheduled for Hyperthermic Intraperitoneal Chemotherapy With Cytoreductive Surgery: Prospective Associations With Morbidity and Mortality. AB - PURPOSE: The current study examined prospective relationships between preoperative depressive symptoms and short-term (30-day morbidity and readmission) and long-term (overall survival) outcomes after hyperthermic intraperitoneal chemotherapy with cytoreductive surgery (HIPEC + CS). METHODS: Ninety-eight patients scheduled for HIPEC + CS completed the Center for Epidemiologic Studies-Depression (CES-D) scale before surgery. Demographic and disease-specific factors and information about morbidity and readmission within 30 days after discharge were gathered from medical records. Survival was measured from date of surgery to death. RESULTS: Twenty-eight percent of patients had CES D scores indicative of clinically significant depressive symptoms. Thirty-day morbidity occurred in 31.9% of patients and readmission in 22.2%. At the time of analysis (median follow-up of 49 months), 71.6% of patients were deceased, with median survival time of 11 months for those who died. After adjusting for relevant preoperative demographic and disease-specific factors, depressive symptoms were associated with greater odds of 30-day morbidity (n = 68; odds ratio, 5.50; 95% CI, 1.23 to 24.73; P = .03) and greater likelihood of 30-day readmission (n = 72; odds ratio, 5.92; 95% CI, 1.27 to 27.64; P = .02). Depressive symptoms were associated with shorter survival after adjustment for preoperative demographic and disease-specific factors (n = 87; hazard ratio, 1.88; 95% CI, 1.07 to 3.31; P = .03). This association was no longer significant when intraoperative/postoperative prognostic variables were added to the statistical model (n = 87; hazard ratio, 1.31; 95% CI, 0.72 to 2.37; P = .37). CONCLUSION: Patients with clinically significant levels of preoperative depressive symptoms are at risk for poor clinical outcomes after HIPEC + CS, including greater risk of 30-day morbidity and readmission. Further research is warranted to determine biobehavioral mechanisms and examine whether effective interventions targeting preoperative depressive symptoms can reduce postoperative risk in this patient population. PMID- 26903576 TI - Re-Examining the Role of Radiation Therapy for Diffuse Large B-Cell Lymphoma in the Modern Era. PMID- 26903577 TI - Associations Between Serum Vitamin D and Adverse Pathology in Men Undergoing Radical Prostatectomy. AB - PURPOSE: Lower serum vitamin D levels have been associated with an increased risk of aggressive prostate cancer. Among men with localized prostate cancer, especially with low- or intermediate-risk disease, vitamin D may serve as an important biomarker of disease aggression. The aim of this study was to assess the relationship between adverse pathology at the time of radical prostatectomy and serum 25-hydroxyvitamin D (25-OH D) levels. METHODS: This cross-sectional study was carried out from 2009 to 2014, nested within a large epidemiologic study of 1,760 healthy controls and men undergoing prostate cancer screening. In total, 190 men underwent radical prostatectomy in the cohort. Adverse pathology was defined as the presence of primary Gleason 4 or any Gleason 5 disease, or extraprostatic extension. Descriptive and multivariate analyses were performed to assess the relationship between 25-OH D and adverse pathology at the time of prostatectomy. RESULTS: Eighty-seven men (45.8%) in this cohort demonstrated adverse pathology at radical prostatectomy. The median age in the cohort was 64.0 years (interquartile range, 59.0 to 67.0). On univariate analysis, men with adverse pathology at radical prostatectomy demonstrated lower median serum 25-OH D (22.7 v 27.0 ng/mL, P = .007) compared with their counterparts. On multivariate analysis, controlling for age, serum prostate specific antigen, and abnormal digital rectal examination, serum 25-OH D less than 30 ng/mL was associated with increased odds of adverse pathology (odds ratio, 2.64; 95% CI, 1.25 to 5.59; P = .01). CONCLUSION: Insufficiency/deficiency of serum 25-OH D is associated with increased odds of adverse pathology in men with localized disease undergoing radical prostatectomy. Serum 25-OH D may serve as a useful biomarker in prostate cancer aggressiveness, which deserves continued study. PMID- 26903575 TI - SIRFLOX: Randomized Phase III Trial Comparing First-Line mFOLFOX6 (Plus or Minus Bevacizumab) Versus mFOLFOX6 (Plus or Minus Bevacizumab) Plus Selective Internal Radiation Therapy in Patients With Metastatic Colorectal Cancer. AB - PURPOSE: SIRFLOX was a randomized, multicenter trial designed to assess the efficacy and safety of adding selective internal radiation therapy (SIRT) using yttrium-90 resin microspheres to standard fluorouracil, leucovorin, and oxaliplatin (FOLFOX)-based chemotherapy in patients with previously untreated metastatic colorectal cancer. PATIENTS AND METHODS: Chemotherapy-naive patients with liver metastases plus or minus limited extrahepatic metastases were randomly assigned to receive either modified FOLFOX (mFOLFOX6; control) or mFOLFOX6 plus SIRT (SIRT) plus or minus bevacizumab. The primary end point was progression-free survival (PFS) at any site as assessed by independent centralized radiology review blinded to study arm. RESULTS: Between October 2006 and April 2013, 530 patients were randomly assigned to treatment (control, 263; SIRT, 267). Median PFS at any site was 10.2 v 10.7 months in control versus SIRT (hazard ratio, 0.93; 95% CI, 0.77 to 1.12; P = .43). Median PFS in the liver by competing risk analysis was 12.6 v 20.5 months in control versus SIRT (hazard ratio, 0.69; 95% CI, 0.55 to 0.90; P = .002). Objective response rates (ORRs) at any site were similar (68.1% v 76.4% in control v SIRT; P = .113). ORR in the liver was improved with the addition of SIRT (68.8% v 78.7% in control v SIRT; P = .042). Grade >= 3 adverse events, including recognized SIRT-related effects, were reported in 73.4% and 85.4% of patients in control versus SIRT. CONCLUSION: The addition of SIRT to FOLFOX-based first-line chemotherapy in patients with liver dominant or liver-only metastatic colorectal cancer did not improve PFS at any site but significantly delayed disease progression in the liver. The safety profile was as expected and was consistent with previous studies. PMID- 26903578 TI - Pulmonary Function in Patients With Germ Cell Cancer Treated With Bleomycin, Etoposide, and Cisplatin. AB - PURPOSE: For patients with germ cell cancer, various pulmonary toxicity risk factors have been hypothesized for treatment with bleomycin, etoposide, and cisplatin (BEP). Because existing studies have shortcomings, we present a large, unselected cohort of patients who have undergone close monitoring of lung function before, during, and after treatment with BEP to disclose valid pulmonary toxicity risk factors. PATIENTS AND METHODS: All patients who were treated with BEP at Rigshospitalet, Copenhagen, Denmark, from 1984 to 2007, were included. Pulmonary function tests (PFTs) that measured the diffusing capacity of the lungs for carbon monoxide (DLCO), forced expiratory volume in 1 second, and forced vital capacity were performed systematically before, during, and after treatment with BEP for 5 years of follow-up. According to local protocol, bleomycin was discontinued if hemoglobin-corrected DLCO (DLCOc) decreased >= 25% compared with pretreatment value. Covariates of possible importance were evaluated with a multiple regression analysis for pretreatment PFTs and with a mixed model for follow-up PFTs. Bleomycin was adjusted on the basis of PFT results and was thus omitted as covariate. RESULTS: Overall, 565 patients were evaluated with a PFT before or after treatment with BEP. During BEP, 15 patients died of progressive disease or toxicity, including one patient from bleomycin-induced pneumonitis. Post-treatment DLCOc decreased significantly, with a rebound during follow-up. Forced expiratory volume in 1 second and forced vital capacity remained unchanged after BEP but increased significantly to levels above pretreatment during follow up. International Germ Cell Cancer Collaborative Group (IGCCCG) prognostic group, mediastinal primary, pulmonary metastases, and smoking all significantly influenced baseline PFT results. Pulmonary surgery, pulmonary embolism, IGCCCG poor prognosis, and smoking influenced PFT during follow-up. Mediastinal primary, pulmonary metastases, age, or doses of cisplatin and etoposide had no influence on follow-up PFT, and renal function did not influence PFT. CONCLUSION: After 5 years of follow-up, pulmonary impairment in patients with germ cell cancer who were treated with BEP was limited. Exceptions were patients treated with pulmonary surgery, those who suffered pulmonary embolism, and those in the IGCCCG poor prognostic group. PMID- 26903580 TI - Morbidity and Mortality of Laparoscopic Versus Open D2 Distal Gastrectomy for Advanced Gastric Cancer: A Randomized Controlled Trial. AB - PURPOSE: The safety and efficacy of radical laparoscopic distal gastrectomy (LG) with D2 lymphadenectomy for the treatment of advanced gastric cancer (AGC) remain controversial. We conducted a randomized controlled trial to compare laparoscopic and conventional open distal gastrectomy with D2 lymph node dissections for AGC. PATIENTS AND METHODS: Between September 2012 and December 2014, 1,056 patients with clinical stage T2-4aN0-3M0 gastric cancer were eligible for inclusion. They were randomly assigned to either the LG with D2 lymphadenectomy group (n = 528) or the open gastrectomy (OG) with D2 lymphadenectomy group (n = 528). Fifteen experienced surgeons from 14 institutions in China participated in the study. The morbidity and mortality within 30 days after surgery between the LG (n = 519) and the OG (n = 520) groups were compared on the basis of the modified intention-to treat principle. Postoperative complications were stratified according to the Clavien-Dindo classification. RESULTS: The compliance rates of D2 lymphadenectomy were similar between the LG and OG groups (99.4% v 99.6%; P = .845). The postoperative morbidity was 15.2% in the LG group and 12.9% in OG group with no significant difference (difference, 2.3%; 95% CI, -1.9 to 6.6; P = .285). The mortality rate was 0.4% for the LG group and zero for the OG group (difference, 0.4%; 95% CI, -0.4 to 1.4; P = .249). The distribution of severity was similar between the two groups (P = .314). CONCLUSION: Experienced surgeons can safely perform LG with D2 lymphadenectomy for AGC. PMID- 26903583 TI - Flow Diverter Therapy With the Pipeline Embolization Device Is Associated With an Elevated Rate of Delayed Fluid-Attenuated Inversion Recovery Lesions. AB - BACKGROUND AND PURPOSE: Flow diversion using the Pipeline Embolization Device is reported as a safe treatment of aneurysms. Complete aneurysm occlusion, however, occurs in a delayed fashion with initial persistent filling of the aneurysm dome. We hypothesized that this transflow across metallic struts may be associated with thromboembolic events. METHODS: Forty-one consecutive patients undergoing aneurysm treatment with the Pipeline Embolization Device and a comparison group of 78 Neuroform stent-mediated embolizations were studied. Patients' charts, procedure notes, platelet function, and anticoagulation state were analyzed. Serial magnetic resonance images were assessed for the presence of newly occurring diffusion-weighted imaging and fluid-attenuated inversion recovery (FLAIR) lesions at multiple postprocedure time ranges (average days post procedure [Pipeline Embolization Device/Neuroform]: T1=1, T2=73/107, T3=174, T4=277/335, and T5=409). In addition, diffusion-weighted imaging or FLAIR burden was estimated by lesional diameter summation. RESULTS: Pipeline patients were more likely to have new ipsilateral FLAIR lesions at all time points studied (30.6% versus 7.2% of patients at T=2 and 34.5% versus 6.2% at T=4). The mean FLAIR burden was significantly increased for Pipeline patients (10.1 versus 0.7 mm at T=2 and 8.8 versus 1.9 mm at T=4). Overall 34% (14/41) of Pipeline patients experienced a new FLAIR lesion at anytime when compared with 10% (8/78) of Neuroform stent-coil patients. Postprocedural diffusion-weighted imaging did not predict future FLAIR lesions suggesting a nonprocedural cause. CONCLUSIONS: The Pipeline Embolization Device is associated with increased rate of de novo FLAIR lesions occurring in a delayed fashion and distinct from perioperative diffusion weighted imaging lesions. The cause and clinical effect of these lesions are unknown and suggest the need for prudent follow-up and evaluation. PMID- 26903579 TI - Trial Design and Objectives for Castration-Resistant Prostate Cancer: Updated Recommendations From the Prostate Cancer Clinical Trials Working Group 3. AB - PURPOSE: Evolving treatments, disease phenotypes, and biology, together with a changing drug development environment, have created the need to revise castration resistant prostate cancer (CRPC) clinical trial recommendations to succeed those from prior Prostate Cancer Clinical Trials Working Groups. METHODS: An international expert committee of prostate cancer clinical investigators (the Prostate Cancer Clinical Trials Working Group 3 [PCWG3]) was reconvened and expanded and met in 2012-2015 to formulate updated criteria on the basis of emerging trial data and validation studies of the Prostate Cancer Clinical Trials Working Group 2 recommendations. RESULTS: PCWG3 recommends that baseline patient assessment include tumor histology, detailed records of prior systemic treatments and responses, and a detailed reporting of disease subtypes based on an anatomic pattern of metastatic spread. New recommendations for trial outcome measures include the time to event end point of symptomatic skeletal events, as well as time to first metastasis and time to progression for trials in the nonmetastatic CRPC state. PCWG3 introduces the concept of no longer clinically benefiting to underscore the distinction between first evidence of progression and the clinical need to terminate or change treatment, and the importance of documenting progression in existing lesions as distinct from the development of new lesions. Serial biologic profiling using tumor samples from biopsies, blood-based diagnostics, and/or imaging is also recommended to gain insight into mechanisms of resistance and to identify predictive biomarkers of sensitivity for use in prospective trials. CONCLUSION: PCWG3 moves drug development closer to unmet needs in clinical practice by focusing on disease manifestations most likely to affect prognosis adversely for therapeutics tested in both nonmetastatic and metastatic CRPC populations. Consultation with regulatory authorities is recommended if a trial is intended to seek support for drug approval. PMID- 26903582 TI - Collateral Status on Baseline Computed Tomographic Angiography and Intra-Arterial Treatment Effect in Patients With Proximal Anterior Circulation Stroke. AB - BACKGROUND AND PURPOSE: Recent randomized trials have proven the benefit of intra arterial treatment (IAT) with retrievable stents in acute ischemic stroke. Patients with poor or absent collaterals (preexistent anastomoses to maintain blood flow in case of a primary vessel occlusion) may gain less clinical benefit from IAT. In this post hoc analysis, we aimed to assess whether the effect of IAT was modified by collateral status on baseline computed tomographic angiography in the Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands (MR CLEAN). METHODS: MR CLEAN was a multicenter, randomized trial of IAT versus no IAT. Primary outcome was the modified Rankin Scale at 90 days. The primary effect parameter was the adjusted common odds ratio for a shift in direction of a better outcome on the modified Rankin Scale. Collaterals were graded from 0 (absent) to 3 (good). We used multivariable ordinal logistic regression analysis with interaction terms to estimate treatment effect modification by collateral status. RESULTS: We found a significant modification of treatment effect by collaterals (P=0.038). The strongest benefit (adjusted common odds ratio 3.2 [95% confidence intervals 1.7 6.2]) was found in patients with good collaterals (grade 3). The adjusted common odds ratio was 1.6 [95% confidence intervals 1.0-2.7] for moderate collaterals (grade 2), 1.2 [95% confidence intervals 0.7-2.3] for poor collaterals (grade 1), and 1.0 [95% confidence intervals 0.1-8.7] for patients with absent collaterals (grade 0). CONCLUSIONS: In MR CLEAN, baseline computed tomographic angiography collateral status modified the treatment effect. The benefit of IAT was greatest in patients with good collaterals on baseline computed tomographic angiography. Treatment benefit appeared less and may be absent in patients with absent or poor collaterals. CLINICAL TRIAL REGISTRATION: URL: http://www.trialregister.nl and http://www.controlled-trials.com. Unique identifier: (NTR)1804 and ISRCTN10888758, respectively. PMID- 26903584 TI - Validating a Pragmatic Approach to Cognitive Screening in Stroke Prevention Clinics Using the Montreal Cognitive Assessment. AB - BACKGROUND AND PURPOSE: The Montreal Cognitive Assessment (MoCA) is used commonly to identify cognitive impairment (CI), but there are multiple published cut points for normal and abnormal. We seek to validate a pragmatic approach to screening for moderate-severe CI, by classifying patients into high-, intermediate-, and low-risk categories. METHODS: A total of 390 participants attending an academic Stroke Prevention Clinic completed the MoCA and more detailed neuropsychological testing. Between April 23, 2012 and April 30, 2014, all consecutive new referrals to the regional Stroke Prevention Clinic who were English-speaking, not severely aphasic, and could see and write well enough to complete neuropsychological testing were assessed for inclusion, and consenting patients were enrolled. CI was defined as >=2 SDs below normal for age and education on at least 2 cognitive subtests. A single cut point for CI was compared with 2 cut points (high sensitivity and high specificity) generated using receiver operator characteristic and area under the curve analyses. The intermediate-risk group contained those scoring between the 2 cut points. RESULTS: Thirty-four percent of participants had a symptomatic or silent stroke, 34% were seen for possible or probable transient ischemic attack, and 32% were diagnosed with other vascular or nonvascular conditions. Using a single cut point, sensitivity and specificity were optimal with MoCA <=22, (sensitivity=60.4%, specificity=89.9%, area under the curve=0.801, positive predictive value=48.5%, negative predictive value=93.5%, positive likelihood ratio=6, and negative likelihood ratio=0.4). Using 2 cut points, sensitivity was optimal with MoCA >=28 (sensitivity=96.2%, negative predictive value =97.6%, and negative likelihood ratio=1.27), and specificity was optimal with MoCA <=22 (specificity=89.9%, positive predictive value=48.5%, and positive likelihood ratio=6). CONCLUSIONS: Stratifying participants into 3 categories facilitates the identification of a homogenous group at low risk for CI, as well as 2 other groups with intermediate and higher risk. This approach could facilitate clinical care pathways and patient selection for research. PMID- 26903585 TI - Preadmission Use of Glucocorticoids and 30-Day Mortality After Stroke. AB - BACKGROUND AND PURPOSE: The prognostic impact of glucocorticoids on stroke mortality remains uncertain. We, therefore, examined whether preadmission use of glucocorticoids is associated with short-term mortality after ischemic stroke, intracerebral hemorrhage (ICH), or subarachnoid hemorrhage (SAH). METHODS: We conducted a nationwide population-based cohort study using medical registries in Denmark. We identified all patients with a first-time inpatient diagnosis of stroke between 2004 and 2012. We categorized glucocorticoid use as current use (last prescription redemption <=90 days before admission), former use, and nonuse. Current use was further classified as new or long-term use. We used Cox regression to compute 30-day mortality rate ratios with 95% confidence intervals (CIs), controlling for confounders. RESULTS: We identified 100 042 patients with a first-time stroke. Of these, 83 735 patients had ischemic stroke, 11 779 had ICH, and 4528 had SAH. Absolute mortality risk was higher for current users compared with nonusers for ischemic stroke (19.5% versus 10.2%), ICH (46.5% versus 34.4%), and SAH (35.0% versus 23.2%). For ischemic stroke, the adjusted 30 day mortality rate ratio was increased among current users compared with nonusers (1.58, 95% CI: 1.46-1.71), driven by the effect of glucocorticoids among new users (1.80, 95% CI: 1.62-1.99). Current users had a more modest increase in the adjusted 30-day mortality rate ratio for hemorrhagic stroke (1.26, 95% CI: 1.09 1.45 for ICH and 1.40, 95% CI: 1.01-1.93 for SAH) compared with nonusers. Former use was not substantially associated with mortality. CONCLUSIONS: Preadmission use of glucocorticoids was associated with increased 30-day mortality among patients with ischemic stroke, ICH, and SAH. PMID- 26903586 TI - Letter by Garcia Pastor et al Regarding Article, "Estimating Weight of Patients With Acute Stroke When Dosing for Thrombolysis". PMID- 26903587 TI - Response to Letter Regarding Article, "Estimating Weight of Patients With Acute Stroke When Dosing for Thrombolysis". PMID- 26903588 TI - Correction. PMID- 26903590 TI - Correction. PMID- 26903589 TI - Correction. PMID- 26903592 TI - Morbidity associated with oral corticosteroids in patients with severe asthma. PMID- 26903591 TI - Leptin secretory dynamics and associated disordered eating psychopathology across the weight spectrum. AB - OBJECTIVE: Leptin secretory dynamics across the weight spectrum and their relationship with disordered eating psychopathology have not been studied. Our objective was to compare leptin secretory dynamics in 13 anorexia nervosa (AN), 12 overweight/obese (OB) and 12 normal-weight women using deconvolution analysis. METHODS: In this cross-sectional study conducted at a tertiary referral center, serum leptin levels were obtained every 20 min from 2000 to 0800 h. Dual energy X-ray absorptiometry was used to measure percent body fat. Disordered eating psychopathology was assessed by the Eating Disorders Examination-Questionnaire (EDE-Q) and the Eating Disorders Inventory-2 (EDI-2). RESULTS: The groups differed for basal leptin secretion (BASAL) (P=0.02). Mean leptin pulse amplitude, pulse mass, total pulsatile secretion (TPS) and area under the curve (AUC) were significantly different between groups before and after adjustment for BASAL (P<0.0001 for all). Leptin AUC correlated strongly with TPS (r=0.97, P<0.0001) and less with BASAL (r=0.35, P=0.03). On multivariate analysis, only TPS was a significant predictor of leptin AUC (P<0.0001). TPS was inversely associated with most EDE-Q and EDI-2 parameters and the associations remained significant for EDE-Q eating concern (P=0.01), and EDI-2 asceticism, ineffectiveness and social insecurity (P<0.05) after adjusting for BASAL. These relationships were not significant when controlled for percent body fat. CONCLUSION: Secretory dynamics of leptin differ across weight spectrum, with mean pulse amplitude, mean pulse mass and TPS being low in AN and high in OB. Pulsatile, rather than basal secretion, is the major contributor to leptin AUC. Decreased pulsatile leptin is associated with disordered eating psychopathology, possibly reflecting low percent body fat in AN. PMID- 26903593 TI - Pectus excavatum in paintings by Jusepe de Ribera (1591-1652). PMID- 26903594 TI - Advancing clinical development pathways for new CFTR modulators in cystic fibrosis. AB - Cystic fibrosis (CF) is a life-shortening genetic disease affecting approximately 70,000 individuals worldwide. Until recently, drug development efforts have emphasised therapies treating downstream signs and symptoms resulting from the underlying CF biological defect: reduced function of the CF transmembrane conductance regulator (CFTR) protein. The current CF drug development landscape has expanded to include therapies that enhance CFTR function by either restoring wild-type CFTR protein expression or increasing (modulating) the function of mutant CFTR proteins in cells. To date, two systemic small-molecule CFTR modulators have been evaluated in pivotal clinical trials in individuals with CF and specific mutant CFTR genotypes that have led to regulatory review and/or approval. Advances in the discovery of CFTR modulators as a promising new class of therapies have been impressive, yet work remains to develop highly effective, disease-modifying modulators for individuals of all CF genotypes. The objectives of this review are to outline the challenges and opportunities in drug development created by systemic genotype-specific CFTR modulators, highlight the advantages of sweat chloride as an established biomarker of CFTR activity to streamline early-phase development and summarise options for later phase clinical trial designs that respond to the adoption of approved genotype-specific modulators into standard of care. An optimal development framework will be needed to move the most promising therapies efficiently through the drug development pipeline and ultimately deliver efficacious and safe therapies to all individuals with CF. PMID- 26903595 TI - The utility of exhaled nitric oxide in patients with suspected asthma. AB - The value of FENO measurements in patients with symptoms suggestive of asthma is unclear. We performed an observational study to assess the ability of FENO to diagnose asthma and to predict response to inhaled corticosteroids (ICS). Our findings suggest FENO is not useful for asthma diagnosis but is accurate at predicting ICS response. PMID- 26903596 TI - Impact on smoking of England's 2012 partial tobacco point of sale display ban: a repeated cross-sectional national study. AB - BACKGROUND: A partial tobacco point of sale (PoS) display ban was introduced in large shops (>280 m2 floor area) in England on 6 April 2012. The aim of this study was to assess the medium-term effects of the partial tobacco PoS display ban on smoking in England. METHODS: Data were used from 129 957 respondents participating in monthly, cross-sectional household surveys of representative samples of the English adult population aged 18+ years from January 2009 to February 2015. Interrupted-time series regression models assessed step changes in the level of current smoking and cigarette consumption in smokers and changes in the trends postban compared with preban. Models were adjusted for sociodemographic variables and e-cigarette use, seasonality and autocorrelation. Potential confounding by cigarette price was accounted for by time, as price was almost perfectly correlated with time. RESULTS: Following the display ban, there was no immediate step level change in smoking (-3.69% change, 95% CI -7.94 to 0.75, p=0.102) or in cigarette consumption (beta -0.183, 95% CI -0.602 to 0.236). There was a significantly steeper decline in smoking post display ban (-0.46% change, 95% CI -0.72 to -0.20, p=0.001). This effect was demonstrated by respondents in manual occupations (-0.62% change, 95% CI -0.72 to -0.20, p=0.001), but not for those in non-manual occupations (-0.42, 95% CI -0.90 to 0.06, p=0.084). Cigarette consumption declined preban period (beta -0.486, 95% CI -0.633 to -0.339, p<0.001), but no significant change in cigarette consumption trend was observed (beta 0.019, 95% CI -0.006 to 0.042, p=0.131). CONCLUSIONS: The partial tobacco PoS display ban introduced in England in April 2012 did not lead to an immediate decline in smoking, but was followed by a decline in the trend of smoking prevalence that could not be accounted for by seasonal factors, e-cigarette use or price changes. PMID- 26903597 TI - Refractory ischaemic chest pain caused by microvascular coronary dysfunction in a large vessel vasculitis. PMID- 26903598 TI - Comparison of patients with early-phase arrhythmogenic right ventricular cardiomyopathy and right ventricular outflow tract ventricular tachycardia. AB - AIMS: Differentiation between early-phase arrhythmogenic right ventricular cardiomyopathy (ARVC) and right ventricular outflow tract (RVOT)-ventricular tachycardia (VT) can be challenging, and correct diagnosis is important. We compared electrocardiogram (ECG) parameters and morphological right ventricular (RV) abnormalities and investigated if ECG and cardiac imaging can help to discriminate early-phase ARVC from RVOT-VT patients. METHODS AND RESULTS: We included 44 consecutive RVOT-VT (47 +/- 14 years) and 121 ARVC patients (42 +/- 17 years). Of the ARVC patients, 77 had definite ARVC and 44 had early-phase ARVC disease. All underwent clinical examination, ECG, and Holter monitoring. Frequency of premature ventricular complexes (PVC) was expressed as percent per total beats/24 h (%PVC), and PVC configuration was recorded. By echocardiography, we assessed indexed RV basal diameter (RVD), indexed RVOT diameter, and RV and left ventricular (LV) function. RV mechanical dispersion (RVMD), reflecting RV contraction heterogeneity, was assessed by speckle-tracking strain echocardiography. RV ejection fraction (RVEF) was assessed by cardiac magnetic resonance imaging (CMR). Patients with early-phase ARVC had lower %PVC by Holter and PVC more frequently originated from the RV lateral free wall (both P < 0.001). RVD was larger (21 +/- 3 vs. 19 +/- 2 mm, P < 0.01), RVMD was more pronounced (22 +/- 15 vs. 15 +/- 13 ms, P = 0.03), and RVEF by CMR was decreased (41 +/- 8 vs. 49 +/- 4%, P < 0.001) in early-phase ARVC vs. RVOT-VT patients. CONCLUSION: Patients with early-phase ARVC had structural abnormalities with lower RVEF, increased RVD, and pronounced RVMD in addition to lower %PVC by Holter compared with RVOT-VT patients. These parameters can help correct diagnosis in patients with unclear phenotypes. PMID- 26903599 TI - Defining the non-vulnerable and vulnerable patients with computed tomography coronary angiography: evaluation of atherosclerotic plaque burden and composition. AB - The shift from coronary plaque stability to plaque instability remains poorly understood despite enormous efforts and expenditures have been assigned to the study of the subject. On the other hand, there have been serious advances in imaging helping us to characterizenon-vulnerable patients The latter has much more value in the clinical decision-making process since it provides high certainty that the patient's probability of a future acute event is low and treatment decisions should be made accordingly. Although coronary plaque rupture is still recognized as the main source of acute thrombotic events, numerous studies have shown that the prediction of events on an individual basis is far more complex and demands a more open approach aimed at characterizing patient risk rather than assessing the risk of thrombosis of a single plaque. Computed tomography coronary angiography (CTCA) has the ability to evaluate non-invasively the extent, burden, severity, and characteristics of coronary artery disease (CAD) and has a close relationship to intravascular ultrasound. On the basis of an excellent negative predictive value with an annualized event rate of ~0.20% assessed over more than 6000 patients, thus providing a 5-year warranty period, CTCA has been identified as the finest non-invasive tool to exclude CAD. This means that CTCA is able to reliably characterize the non-vulnerable patient. Conversely, in the past few years, several studies have attempted to establish CTCA-derived predictors of acute coronary syndromes, both from a lesion level and a patient level basis with very low positive predictive value, thus questioning the vulnerable patient/plaque concept. PMID- 26903600 TI - Sororin actively maintains sister chromatid cohesion. AB - Cohesion between sister chromatids is established during DNA replication but needs to be maintained to enable proper chromosome-spindle attachments in mitosis or meiosis. Cohesion is mediated by cohesin, but also depends on cohesin acetylation and sororin. Sororin contributes to cohesion by stabilizing cohesin on DNA. Sororin achieves this by inhibiting WAPL, which otherwise releases cohesin from DNA and destroys cohesion. Here we describe mouse models which enable the controlled depletion of sororin by gene deletion or auxin-induced degradation. We show that sororin is essential for embryonic development, cohesion maintenance, and proper chromosome segregation. We further show that the acetyltransferases ESCO1 and ESCO2 are essential for stabilizing cohesin on chromatin, that their only function in this process is to acetylate cohesin's SMC3 subunit, and that DNA replication is also required for stable cohesin chromatin interactions. Unexpectedly, we find that sororin interacts dynamically with the cohesin complexes it stabilizes. This implies that sororin recruitment to cohesin does not depend on the DNA replication machinery or process itself, but on a property that cohesin acquires during cohesion establishment. PMID- 26903601 TI - Stat3 promotes mitochondrial transcription and oxidative respiration during maintenance and induction of naive pluripotency. AB - Transcription factor Stat3 directs self-renewal of pluripotent mouse embryonic stem (ES) cells downstream of the cytokine leukemia inhibitory factor (LIF). Stat3 upregulates pivotal transcription factors in the ES cell gene regulatory network to sustain naive identity. Stat3 also contributes to the rapid proliferation of ES cells. Here, we show that Stat3 increases the expression of mitochondrial-encoded transcripts and enhances oxidative metabolism. Chromatin immunoprecipitation reveals that Stat3 binds to the mitochondrial genome, consistent with direct transcriptional regulation. An engineered form of Stat3 that localizes predominantly to mitochondria is sufficient to support enhanced proliferation of ES cells, but not to maintain their undifferentiated phenotype. Furthermore, during reprogramming from primed to naive states of pluripotency, Stat3 similarly upregulates mitochondrial transcripts and facilitates metabolic resetting. These findings suggest that the potent stimulation of naive pluripotency by LIF/Stat3 is attributable to parallel and synergistic induction of both mitochondrial respiration and nuclear transcription factors. PMID- 26903603 TI - Willingness to Pay for Mosquito Control in Key West, Florida and Tucson, Arizona. AB - Mosquito-borne illnesses like West Nile virus (WNV) and dengue are growing threats to the United States. Proactive mosquito control is one strategy to reduce the risk of disease transmission. In 2012, we measured the public's willingness to pay (WTP) for increased mosquito control in two cities: Key West, FL, where there have been recent dengue outbreaks, and Tucson, AZ, where dengue vectors are established and WNV has been circulating for over a decade. Nearly three quarters of respondents in both cities (74% in Tucson and 73% in Key West) would be willing to pay $25 or more annually toward an increase in publicly funded mosquito control efforts. WTP was positively associated with income (both cities), education (Key West), and perceived mosquito abundance (Tucson). Concerns about environmental impacts of mosquito control were associated with lower WTP in Key West. Expanded mosquito control efforts should incorporate public opinion as they respond to evolving disease risks. PMID- 26903602 TI - Ribonuclease H2 mutations induce a cGAS/STING-dependent innate immune response. AB - Aicardi-Goutieres syndrome (AGS) provides a monogenic model of nucleic acid mediated inflammation relevant to the pathogenesis of systemic autoimmunity. Mutations that impair ribonuclease (RNase) H2 enzyme function are the most frequent cause of this autoinflammatory disorder of childhood and are also associated with systemic lupus erythematosus. Reduced processing of eitherRNA:DNAhybrid or genome-embedded ribonucleotide substrates is thought to lead to activation of a yet undefined nucleic acid-sensing pathway. Here, we establishRnaseh2b(A174T/A174T)knock-in mice as a subclinical model of disease, identifying significant interferon-stimulated gene (ISG) transcript upregulation that recapitulates theISGsignature seen inAGSpatients. The inflammatory response is dependent on the nucleic acid sensor cyclicGMP-AMPsynthase (cGAS) and its adaptorSTINGand is associated with reduced cellular ribonucleotide excision repair activity and increasedDNAdamage. This suggests thatcGAS/STINGis a key nucleic acid-sensing pathway relevant toAGS, providing additional insight into disease pathogenesis relevant to the development of therapeutics for this childhood-onset interferonopathy and adult systemic autoimmune disorders. PMID- 26903604 TI - Immunoproliferative Small Intestinal Disease Associated with Overwhelming Polymicrobial Gastrointestinal Infection with Transformation to Diffuse Large B cell Lymphoma. AB - Immunoproliferative small intestinal disease (IPSID) is an extra-nodal B-cell lymphoma most commonly described in the Mediterranean, Africa, and Asia. It is associated with poverty and poor sanitation, and is rarely encountered in developed countries. A 26-year-old previously healthy, Marshallese male was transferred to our facility with a 6-month history of watery diarrhea, weakness, and cachexia refractory to multiple short courses of oral antibiotics. Stool cultures grew Campylobacter jejuni and Vibrio fluvialis. Endoscopic evaluation showed histologic evidence of Helicobacter pylori gastritis and gross evidence of whipworm infection found in the colon. Mesenteric lymph node biopsy cultures grew Escherichia coli. Histopathology and immunohistochemical stains of the small intestine were consistent with IPSID. He subsequently transformed to diffuse large B-cell lymphoma (DLBCL) with tonsillar involvement despite treatment with rituximab and an extended course of antibiotics. Systemic chemotherapy with six cycles of rituximab, cyclophosphamide, vincristine, doxorubicin, prednisone, and lenalidomide, resulted in remission of his diffuse B cell lymphoma. This case is illustrative of IPSID developing in a previously healthy individual due to overwhelming polymicrobial gastrointestinal infection by C. jejuni and other enteric pathogens with subsequent transformation to an aggressive DLBCL. IPSID should be considered in residents of developing countries presenting with refractory chronic diarrhea, weight loss, and mesenteric lymphadenopathy. PMID- 26903605 TI - Intralesional Pentamidine: A Novel Therapy for Single Lesions of Bolivian Cutaneous Leishmaniasis. AB - A novel therapy, intralesional (IL) pentamidine, was compared to intralesional therapy with antimony (ILSb), a World Health Organization-recommended therapy, for single Bolivian Leishmania braziliensis lesions. In Study 1, 90 patients were randomized equally between three injections of ILSb over 5 days, five injections of ILSb over 11 days, and three injections of IL pentamidine (120 MUg/mm(2)lesion area [ILPenta-120-3]) over 5 days. Cure rates at 6 months were 57% for ILSb-3 injections, 73% for ILSb-5 injections, and 72% for ILPenta-120-3 injections. Adverse effects were local irritation and injection-site pain-ILSb (60 patients): mild (25), moderate (4); IL pentamidine (30 patients): mild (4), moderate (3). In Study 2, 60 patients were randomized equally between five injections of ILSb and three injections of a double dose of IL pentamidine (240 MUg/mm(2)[ILPenta-240 3]). In Study 2, cure rates were 67% for ILSb-5 injections and 73% for ILPenta 240-3. For three IL injections of pentamidine, efficacy was optimized at a dose of 120 MUg/mm(2)lesion area. The cure rate of that regimen was similar to that for ILSb-5 injections and nonstatistically larger than that of ILSb-3 injections. IL pentamidine is an attractive alternative to ILSb on the basis of efficacy for Bolivian L. braziliensis, the threat of Sb-resistant parasites, tolerance, and patient convenience of three visits over 5 days. PMID- 26903606 TI - Development of Type 2, But Not Type 1, Leprosy Reactions is Associated with a Severe Reduction of Circulating and In situ Regulatory T-Cells. AB - Leprosy is frequently complicated by the appearance of reactions that are difficult to treat and are the main cause of sequelae. We speculated that disturbances in regulatory T-cells (Tregs) could play a role in leprosy reactions. We determined the frequency of circulating Tregs in patients with type 1 reaction (T1R) and type 2 reaction (T2R). The in situ frequency of Tregs and interleukin (IL)-17, IL-6, and transforming growth factor beta (TGF)-beta expressing cells was also determined. T2R patients showed markedly lower number of circulating and in situ Tregs than T1R patients and controls. This decrease was paralleled by increased in situ IL-17 expression but decreased TGF-beta expression. Biopsies from T1R and T2R patients before the reaction episodes showed similar number of forkhead box protein P3+ (FoxP3+) and IL-17+ cells. However, in biopsies taken during the reaction, T2R patients showed a decrease in Tregs and increase in IL-17+ cells, whereas T1R patients showed the opposite: Tregs increased but IL-17+ cells decreased. We also found decreased expansion of Tregs upon in vitro stimulation with Mycobacterium leprae and a trend for lower expression of FoxP3 and the immunosuppressive molecule cytotoxic T-lymphocyte associated protein 4 (CTLA-4) in T2R Tregs. Our results provide some evidence to the hypothesis that, in T2R, downmodulation of Tregs may favor the development of T-helper-17 responses that characterize this reaction. PMID- 26903608 TI - Ascaris lumbricoides Infection Following School-Based Deworming in Western Kenya: Assessing the Role of Pupils' School and Home Water, Sanitation, and Hygiene Exposures. AB - Water, sanitation, and hygiene (WaSH) technologies and behaviors can prevent infection by soil-transmitted helminth species independently, but may also interact in complex ways. However, these interactions are poorly understood. The purpose of this study was to characterize how school and home WaSH exposures were associated with Ascaris lumbricoides infection and to identify relevant interactions between separate WaSH technologies and behaviors. A study was conducted among 4,404 children attending 51 primary schools in western Kenya. We used multivariable mixed effects logistic regression to characterize how various WaSH exposures were associated with A. lumbricoides infection after annual school based deworming. Few WaSH behaviors and technologies were independently associated with A. lumbricoides infection. However, by considering relevant interdependencies between variables, important associations were elucidated. The association between handwashing and A. lumbricoides depended largely upon the pupils' access to an improved water source. Among pupils who had access to improved water sources, A. lumbricoides prevalence was lower for those who handwashed both at school and home compared with neither place (odds ratio: 0.38, 95% confidence interval: 0.18-0.83; P = 0.01). This study contributes to a further understanding of the impact of WaSH on A. lumbricoides infection and shows the importance of accounting for interactions between WaSH technologies and behaviors. PMID- 26903607 TI - A Global Genomic Characterization of Nairoviruses Identifies Nine Discrete Genogroups with Distinctive Structural Characteristics and Host-Vector Associations. AB - Nairoviruses are primarily tick-borne bunyaviruses, some of which are known to cause mild-to-severe febrile illness in humans or livestock. We describe the genome sequences of 11 poorly characterized nairoviruses that have ecological associations with either birds (Farallon, Punta Salinas, Sapphire II, Zirqa, Avalon, Clo Mor, Taggert, and Abu Hammad viruses), rodents (Qalyub and Bandia viruses), or camels (Dera Ghazi Khan virus). Global phylogenetic analyses of proteins encoded in the L, M, and S RNA segments of these and 20 other available nairovirus genomes identified nine well-supported genogroups (Nairobi sheep disease, Thiafora, Sakhalin, Keterah, Qalyub, Kasokero, Dera Ghazi Khan, Hughes, and Tamdy). Genogroup-specific structural variations were evident, particularly in the M segment encoding a polyprotein from which virion envelope glycoproteins (Gn and Gc) are generated by proteolytic processing. Structural variations include the extension, abbreviation, or absence sequences encoding an O glycosylated mucin-like protein in the N-terminal domain, distinctive patterns of conserved cysteine residues in the GP38-like domain, insertion of sequences encoding a double-membrane-spanning protein (NSm) between the Gn and Gc domains, and the presence of an alternative long open reading frame encoding a viroporin like transmembrane protein (Gx). We also observed strong genogroup-specific associations with categories of hosts and tick vectors. PMID- 26903609 TI - A Health Care Worker with Ebola Virus Disease and Adverse Prognostic Factors Treated in Sierra Leone. AB - We describe the management of a Sierra Leonean health care worker with severe Ebola virus disease complicated by diarrhea, significant electrolyte disturbances, and falciparum malaria coinfection. With additional resources and staffing, high quality care can be provided to patients with Ebola infection and adverse prognostic factors in west Africa. PMID- 26903610 TI - Zika Virus Emergence and Expansion: Lessons Learned from Dengue and Chikungunya May Not Provide All the Answers. AB - Following the emergence of Zika in the past decade, there are lessons to be learned from similar emergence events of dengue (DENV) and chikungunya (CHIKV). Specifically, as Zika emerges in the Americas there is a natural tendency to apply the knowledge base of DENV and CHIKV to mitigation and control of a virus with such a similar transmission system. However, there are marked differences that may preclude such broad stroke application of this knowledge base without making potentially faulty assumptions. Herein, Zika virus (ZIKV) transmission is reviewed, and the commonalities among these three arboviruses are discussed. Importantly, the divergence of this particular arbovirus is discussed, as is the need to develop ZIKV-specific knowledge base for mitigation of this disease. Specifically reviewed are 1) emergence and persistence patterns, 2) genetic and phenotypic diversity, 3) vector host range, and finally, 4) alternate transmission routes and added complexity of ZIKV transmission and presentation. PMID- 26903611 TI - Spectrum of Imported Infectious Diseases: A Comparative Prevalence Study of 16,817 German Travelers and 977 Immigrants from the Tropics and Subtropics. AB - The aim of this study was to assess the spectrum of imported infectious diseases (IDs) among patients consulting the University of Munich, Germany, between 1999 and 2014 after being in the sub-/tropics. The analysis investigated complete data sets of 16,817 diseased German travelers (2,318 business travelers, 4,029 all inclusive travelers, and 10,470 backpackers) returning from Latin America (3,225), Africa (4,865), or Asia (8,727), and 977 diseased immigrants, originating from the same regions (112, 654 and 211 respectively). The most frequent symptoms assessed were diarrhea (38%), fever (29%), and skin disorder (22%). The most frequent IDs detected were intestinal infections with species of Blastocystis(900),Giardia(730),Campylobacter(556),Shigella(209), and Salmonella(183). Also frequently observed were cutaneous larva migrans (379), dengue (257), and malaria (160). The number of IDs with significantly elevated proportions was higher among backpackers (18) and immigrants (17), especially among those from Africa (18) and Asia (17), whereas it was lower for business travelers (5), all-inclusive travelers (1), and those from Latin America (5). This study demonstrates a large spectrum of imported IDs among returning German travelers and immigrants, which varies greatly based not only on travel destination and origin of immigrants, but also on type of travel. PMID- 26903612 TI - Identifying Flood-Related Infectious Diseases in Anhui Province, China: A Spatial and Temporal Analysis. AB - The aim of this study was to explore infectious diseases related to the 2007 Huai River flood in Anhui Province, China. The study was based on the notified incidences of infectious diseases between June 29 and July 25 from 2004 to 2011. Daily incidences of notified diseases in 2007 were compared with the corresponding daily incidences during the same period in the other years (from 2004 to 2011, except 2007) by Poisson regression analysis. Spatial autocorrelation analysis was used to test the distribution pattern of the diseases. Spatial regression models were then performed to examine the association between the incidence of each disease and flood, considering lag effects and other confounders. After controlling the other meteorological and socioeconomic factors, malaria (odds ratio [OR] = 3.67, 95% confidence interval [CI] = 1.77-7.61), diarrhea (OR = 2.16, 95% CI = 1.24-3.78), and hepatitis A virus (HAV) infection (OR = 6.11, 95% CI = 1.04-35.84) were significantly related to the 2007 Huai River flood both from the spatial and temporal analyses. Special attention should be given to develop public health preparation and interventions with a focus on malaria, diarrhea, and HAV infection, in the study region. PMID- 26903614 TI - The Spectrum of Chromobacterium violaceum Infections from a Single Geographic Location. AB - Chromobacterium violaceum is a bacterium associated with soil and water exposure in tropical regions and causes rare and serious clinical infections that are often fatal. We reviewed the demographic and clinical details of 28 patients with C. violaceum detected over 15 years from 2000 to 2015, from the Top End of the Northern Territory. Of these patients, 18 had infections attributable toC. violaceum Patients with infections were more commonly male (55.6%), and in the 16 to 60-year (61.1%) age group. Skin and soft tissue infections (50%), predominantly involving the limbs, were the major clinical manifestation. Water, mud exposure, and trauma were all noted as precipitating circumstances and comorbidities were present in 61.1% of the patients with infections. Of the 28 patients, 10 (35.8%) had C. violaceum isolated as an incidental finding or as asymptomatic colonization; these 10 patients did not require or receive therapy for C. violaceum bacterial infections. There were no relapsing infections in this group.Chromobacterium violaceum remains a serious infection, with seven patients (25%) in our series requiring intensive care management. However, the mortality rate (7.1%) in our series was far lower than previously described. This case series of C. violaceum infections from a single geographic area provides additional information of the characteristics of infection with this pathogen. PMID- 26903615 TI - Earlobe Inflammation from a Palm Thorn Injury. AB - Injury from the thorn of a palm tree is characterized by a prolonged, painful inflammatory reaction. Even when the source of the inflammation is diagnosed, appropriate treatment is usually delayed because family doctors are not familiar with the entity. Penetration of a palm thorn into the earlobe is an unrecognized cause of local inflammation. We describe a case of injury from a palm tree thorn in this uncommon site. We present the technique of transillumination for the identification and removal of the palm thorn. PMID- 26903613 TI - Surveying the Knowledge and Practices of Health Professionals in China, India, Iran, and Mexico on Treating Tuberculosis. AB - Research evidence continues to reveal findings important for health professionals' clinical practices, yet it is not consistently disseminated to those who can use it. The resulting deficits in knowledge and service provision may be especially pronounced in low- and middle-income countries that have greater resource constraints. Tuberculosis treatment is an important area for assessing professionals' knowledge and practices because of the effectiveness of existing treatments and recognized gaps in professionals' knowledge about treatment. This study surveyed 384 health professionals in China, India, Iran, and Mexico on their knowledge and practices related to tuberculosis treatment. Few respondents correctly answered all five knowledge questions (12%) or self reported performing all five recommended clinical practices "often or very often" (3%). Factors associated with higher knowledge scores included clinical specialization and working with researchers. Factors associated with better practices included training in the care of tuberculosis patients, being based in a hospital, trusting systematic reviews of randomized controlled double-blind trials, and reading summaries of articles, reports, and reviews. This study highlights several strategies that may prove effective in improving health professionals' knowledge and practices related to tuberculosis treatment. Facilitating interactions with researchers and training in acquiring systematic reviews may be especially helpful. PMID- 26903616 TI - Emergence of functional subnetworks in layer 2/3 cortex induced by sequential spikes in vivo. AB - During cortical circuit development in the mammalian brain, groups of excitatory neurons that receive similar sensory information form microcircuits. However, cellular mechanisms underlying cortical microcircuit development remain poorly understood. Here we implemented combined two-photon imaging and photolysis in vivo to monitor and manipulate neuronal activities to study the processes underlying activity-dependent circuit changes. We found that repeated triggering of spike trains in a randomly chosen group of layer 2/3 pyramidal neurons in the somatosensory cortex triggered long-term plasticity of circuits (LTPc), resulting in the increased probability that the selected neurons would fire when action potentials of individual neurons in the group were evoked. Significant firing pattern changes were observed more frequently in the selected group of neurons than in neighboring control neurons, and the induction was dependent on the time interval between spikes, N-methyl-D-aspartate (NMDA) receptor activation, and Calcium/calmodulin-dependent protein kinase II (CaMKII) activation. In addition, LTPc was associated with an increase of activity from a portion of neighboring neurons with different probabilities. Thus, our results demonstrate that the formation of functional microcircuits requires broad network changes and that its directionality is nonrandom, which may be a general feature of cortical circuit assembly in the mammalian cortex. PMID- 26903617 TI - Phylogenetically resolving epidemiologic linkage. AB - Although the use of phylogenetic trees in epidemiological investigations has become commonplace, their epidemiological interpretation has not been systematically evaluated. Here, we use an HIV-1 within-host coalescent model to probabilistically evaluate transmission histories of two epidemiologically linked hosts. Previous critique of phylogenetic reconstruction has claimed that direction of transmission is difficult to infer, and that the existence of unsampled intermediary links or common sources can never be excluded. The phylogenetic relationship between the HIV populations of epidemiologically linked hosts can be classified into six types of trees, based on cladistic relationships and whether the reconstruction is consistent with the true transmission history or not. We show that the direction of transmission and whether unsampled intermediary links or common sources existed make very different predictions about expected phylogenetic relationships: (i) Direction of transmission can often be established when paraphyly exists, (ii) intermediary links can be excluded when multiple lineages were transmitted, and (iii) when the sampled individuals' HIV populations both are monophyletic a common source was likely the origin. Inconsistent results, suggesting the wrong transmission direction, were generally rare. In addition, the expected tree topology also depends on the number of transmitted lineages, the sample size, the time of the sample relative to transmission, and how fast the diversity increases after infection. Typically, 20 or more sequences per subject give robust results. We confirm our theoretical evaluations with analyses of real transmission histories and discuss how our findings should aid in interpreting phylogenetic results. PMID- 26903618 TI - Convective flow reversal in self-powered enzyme micropumps. AB - Surface-bound enzymes can act as pumps that drive large-scale fluid flows in the presence of their substrates or promoters. Thus, enzymatic catalysis can be harnessed for "on demand" pumping in nano- and microfluidic devices powered by an intrinsic energy source. The mechanisms controlling the pumping have not, however, been completely elucidated. Herein, we combine theory and experiments to demonstrate a previously unreported spatiotemporal variation in pumping behavior in urease-based pumps and uncover the mechanisms behind these dynamics. We developed a theoretical model for the transduction of chemical energy into mechanical fluid flow in these systems, capturing buoyancy effects due to the solution containing nonuniform concentrations of substrate and product. We find that the qualitative features of the flow depend on the ratios of diffusivities delta=D(P)/D(S) and expansion coefficients beta=beta(P)/beta(S) of the reaction substrate (S) and product (P). If delta>1 and delta>beta (or if delta<1 and delta=4 newform f?S(k)(Gamma(0)((N)) is the generating function for the critical values of L(f,s) . It has a functional equation relating r(f)(z) to r(f)(-1/Nz). We prove the Riemann hypothesis for these polynomials: that the zeros of r(f)(z) lie on the circle |z|=1/?N . We prove that these zeros are equidistributed when either k or N is large. PMID- 26903627 TI - Quantitative proteomic analyses of mammary organoids reveals distinct signatures after exposure to environmental chemicals. AB - Common environmental contaminants such as bisphenols and phthalates and persistent contaminants such as polychlorinated biphenyls are thought to influence tissue homeostasis and carcinogenesis by acting as disrupters of endocrine function. In this study we investigated the direct effects of exposure to bisphenol A (BPA), mono-n-butyl phthalate (Pht), and polychlorinated biphenyl 153 (PCB153) on the proteome of primary organotypic cultures of the mouse mammary gland. At low-nanomolar doses each of these agents induced distinct effects on the proteomes of these cultures. Although BPA treatment produced effects that were similar to those induced by estradiol, there were some notable differences, including a reduction in the abundance of retinoblastoma-associated protein and increases in the Rho GTPases Ras-related C3 botulinum toxin substrate 1 (Rac1) and cell division cycle protein CDC42. Both Pht and PCB153 induced changes that were distinct from those induced by estrogen, including decreased levels of the transcriptional corepressor C-terminal binding protein 1. Interestingly, the three chemicals appeared to alter the abundance of distinct splice forms of many proteins as well as the abundance of several proteins that regulate RNA splicing. Our combined results indicate that the three classes of chemical have distinct effects on the proteome of normal mouse mammary cultures, some estrogen-like but most estrogen independent, that influence diverse biological processes including apoptosis, cell adhesion, and proliferation. PMID- 26903629 TI - Sterol and genomic analyses validate the sponge biomarker hypothesis. AB - Molecular fossils (or biomarkers) are key to unraveling the deep history of eukaryotes, especially in the absence of traditional fossils. In this regard, the sterane 24-isopropylcholestane has been proposed as a molecular fossil for sponges, and could represent the oldest evidence for animal life. The sterane is found in rocks ~650-540 million y old, and its sterol precursor (24 isopropylcholesterol, or 24-ipc) is synthesized today by certain sea sponges. However, 24-ipc is also produced in trace amounts by distantly related pelagophyte algae, whereas only a few close relatives of sponges have been assayed for sterols. In this study, we analyzed the sterol and gene repertoires of four taxa (Salpingoeca rosetta, Capsaspora owczarzaki, Sphaeroforma arctica, and Creolimax fragrantissima), which collectively represent the major living animal outgroups. We discovered that all four taxa lack C30 sterols, including 24 ipc. By building phylogenetic trees for key enzymes in 24-ipc biosynthesis, we identified a candidate gene (carbon-24/28 sterol methyltransferase, or SMT) responsible for 24-ipc production. Our results suggest that pelagophytes and sponges independently evolved C30 sterol biosynthesis through clade-specific SMT duplications. Using a molecular clock approach, we demonstrate that the relevant sponge SMT duplication event overlapped with the appearance of 24 isopropylcholestanes in the Neoproterozoic, but that the algal SMT duplication event occurred later in the Phanerozoic. Subsequently, pelagophyte algae and their relatives are an unlikely alternative to sponges as a source of Neoproterozoic 24-isopropylcholestanes, consistent with growing evidence that sponges evolved long before the Cambrian explosion ~542 million y ago. PMID- 26903630 TI - A PERIOD3 variant causes a circadian phenotype and is associated with a seasonal mood trait. AB - In humans, the connection between sleep and mood has long been recognized, although direct molecular evidence is lacking. We identified two rare variants in the circadian clock gene PERIOD3 (PER3-P415A/H417R) in humans with familial advanced sleep phase accompanied by higher Beck Depression Inventory and seasonality scores. hPER3-P415A/H417R transgenic mice showed an altered circadian period under constant light and exhibited phase shifts of the sleep-wake cycle in a short light period (photoperiod) paradigm. Molecular characterization revealed that the rare variants destabilized PER3 and failed to stabilize PERIOD1/2 proteins, which play critical roles in circadian timing. Although hPER3 P415A/H417R-Tg mice showed a mild depression-like phenotype, Per3 knockout mice demonstrated consistent depression-like behavior, particularly when studied under a short photoperiod, supporting a possible role for PER3 in mood regulation. These findings suggest that PER3 may be a nexus for sleep and mood regulation while fine-tuning these processes to adapt to seasonal changes. PMID- 26903631 TI - Solar photothermochemical alkane reverse combustion. AB - A one-step, gas-phase photothermocatalytic process for the synthesis of hydrocarbons, including liquid alkanes, aromatics, and oxygenates, with carbon numbers (Cn) up to C13, from CO2 and water is demonstrated in a flow photoreactor operating at elevated temperatures (180-200 degrees C) and pressures (1-6 bar) using a 5% cobalt on TiO2 catalyst and under UV irradiation. A parametric study of temperature, pressure, and partial pressure ratio revealed that temperatures in excess of 160 degrees C are needed to obtain the higher Cn products in quantity and that the product distribution shifts toward higher Cn products with increasing pressure. In the best run so far, over 13% by mass of the products were C5+ hydrocarbons and some of these, i.e., octane, are drop-in replacements for existing liquid hydrocarbons fuels. Dioxygen was detected in yields ranging between 64% and 150%. In principle, this tandem photochemical-thermochemical process, fitted with a photocatalyst better matched to the solar spectrum, could provide a cheap and direct method to produce liquid hydrocarbons from CO2 and water via a solar process which uses concentrated sunlight for both photochemical excitation to generate high-energy intermediates and heat to drive important thermochemical carbon-chain-forming reactions. PMID- 26903632 TI - Marine microplastics spell big problems for future generations. PMID- 26903635 TI - Anthropogenic climate change drives shift and shuffle in North Atlantic phytoplankton communities. AB - Anthropogenic climate change has shifted the biogeography and phenology of many terrestrial and marine species. Marine phytoplankton communities appear sensitive to climate change, yet understanding of how individual species may respond to anthropogenic climate change remains limited. Here, using historical environmental and phytoplankton observations, we characterize the realized ecological niches for 87 North Atlantic diatom and dinoflagellate taxa and project changes in species biogeography between mean historical (1951-2000) and future (2051-2100) ocean conditions. We find that the central positions of the core range of 74% of taxa shift poleward at a median rate of 12.9 km per decade (km?dec(-1)), and 90% of taxa shift eastward at a median rate of 42.7 km?dec(-1) The poleward shift is faster than previously reported for marine taxa, and the predominance of longitudinal shifts is driven by dynamic changes in multiple environmental drivers, rather than a strictly poleward, temperature-driven redistribution of ocean habitats. A century of climate change significantly shuffles community composition by a basin-wide median value of 16%, compared with seasonal variations of 46%. The North Atlantic phytoplankton community appears poised for marked shift and shuffle, which may have broad effects on food webs and biogeochemical cycles. PMID- 26903633 TI - Contrasting responses within a single neuron class enable sex-specific attraction in Caenorhabditis elegans. AB - Animals find mates and food, and avoid predators, by navigating to regions within a favorable range of available sensory cues. How are these ranges set and recognized? Here we show that male Caenorhabditis elegans exhibit strong concentration preferences for sex-specific small molecule cues secreted by hermaphrodites, and that these preferences emerge from the collective dynamics of a single male-specific class of neurons, the cephalic sensory neurons (CEMs). Within a single worm, CEM responses are dissimilar, not determined by anatomical classification and can be excitatory or inhibitory. Response kinetics vary by concentration, suggesting a mechanism for establishing preferences. CEM responses are enhanced in the absence of synaptic transmission, and worms with only one intact CEM show nonpreferential attraction to all concentrations of ascaroside for which CEM is the primary sensor, suggesting that synaptic modulation of CEM responses is necessary for establishing preferences. A heterogeneous concentration-dependent sensory representation thus appears to allow a single neural class to set behavioral preferences and recognize ranges of sensory cues. PMID- 26903634 TI - Differences in codon bias and GC content contribute to the balanced expression of TLR7 and TLR9. AB - The innate immune system detects diverse microbial species with a limited repertoire of immune receptors that recognize nucleic acids. The cost of this immune surveillance strategy is the potential for inappropriate recognition of self-derived nucleic acids and subsequent autoimmune disease. The relative expression of two closely related receptors, Toll-like receptor (TLR) 7 and TLR9, is balanced to allow recognition of microbial nucleic acids while limiting recognition of self-derived nucleic acids. Situations that tilt this balance toward TLR7 promote inappropriate responses, including autoimmunity; therefore, tight control of expression is critical for proper homeostasis. Here we report that differences in codon bias limit TLR7 expression relative to TLR9. Codon optimization of Tlr7 increases protein levels as well as responses to ligands, but, unexpectedly, these changes only modestly affect translation. Instead, we find that much of the benefit attributed to codon optimization is actually the result of enhanced transcription. Our findings, together with other recent examples, challenge the dogma that codon optimization primarily increases translation. We propose that suboptimal codon bias, which correlates with low guanine-cytosine (GC) content, limits transcription of certain genes. This mechanism may establish low levels of proteins whose overexpression leads to particularly deleterious effects, such as TLR7. PMID- 26903637 TI - Parallel computation with molecular-motor-propelled agents in nanofabricated networks. AB - The combinatorial nature of many important mathematical problems, including nondeterministic-polynomial-time (NP)-complete problems, places a severe limitation on the problem size that can be solved with conventional, sequentially operating electronic computers. There have been significant efforts in conceiving parallel-computation approaches in the past, for example: DNA computation, quantum computation, and microfluidics-based computation. However, these approaches have not proven, so far, to be scalable and practical from a fabrication and operational perspective. Here, we report the foundations of an alternative parallel-computation system in which a given combinatorial problem is encoded into a graphical, modular network that is embedded in a nanofabricated planar device. Exploring the network in a parallel fashion using a large number of independent, molecular-motor-propelled agents then solves the mathematical problem. This approach uses orders of magnitude less energy than conventional computers, thus addressing issues related to power consumption and heat dissipation. We provide a proof-of-concept demonstration of such a device by solving, in a parallel fashion, the small instance {2, 5, 9} of the subset sum problem, which is a benchmark NP-complete problem. Finally, we discuss the technical advances necessary to make our system scalable with presently available technology. PMID- 26903638 TI - Intensification of phosphorus cycling in China since the 1600s. AB - Phosphorus (P) is an essential nutrient for living systems with emerging sustainability challenges related to supply uncertainty and aquatic eutrophication. However, its long-term temporal dynamics and subsequent effects on freshwater ecosystems are still unclear. Here, we quantify the P pathways across China over the past four centuries with a life cycle process-balanced model and evaluate the concomitant potential for eutrophication with a spatial resolution of 5 arc-minutes in 2012. We find that P cycling in China has been artificially intensified during this period to sustain the increasing population and its demand for animal protein-based diets, with continuous accumulations in inland waters and lands. In the past decade, China's international trade of P involves net exports of P chemicals and net imports of downstream crops, specifically soybeans from the United States, Brazil, and Argentina. The contribution of crop products to per capita food P demand, namely, the P directly consumed by humans, declined from over 98% before the 1950s to 76% in 2012, even though there was little change in per capita food P demand. Anthropogenic P losses to freshwater and their eutrophication potential clustered in wealthy coastal regions with dense populations. We estimate that Chinese P reserve depletion could be postponed for over 20 y by more efficient life cycle P management. Our results highlight the importance of closing the P cycle to achieve the cobenefits of P resource conservation and eutrophication mitigation in the world's most rapidly developing economy. PMID- 26903636 TI - Identification and quantitation of lipid C=C location isomers: A shotgun lipidomics approach enabled by photochemical reaction. AB - The field of lipidomics has been significantly advanced by mass spectrometric analysis. The distinction and quantitation of the unsaturated lipid isomers, however, remain a long-standing challenge. In this study, we have developed an analytical tool for both identification and quantitation of lipid C=C location isomers from complex mixtures using online Paterno-Buchi reaction coupled with tandem mass spectrometry (MS/MS). The potential of this method has been demonstrated with an implementation into shotgun lipid analysis of animal tissues. Among 96 of the unsaturated fatty acids and glycerophospholipids identified from rat brain tissue, 50% of them were found as mixtures of C=C location isomers; for the first time, to our knowledge, the quantitative information of lipid C=C isomers from a broad range of classes was obtained. This method also enabled facile cross-tissue examinations, which revealed significant changes in C=C location isomer compositions of a series of fatty acids and glycerophospholipid (GP) species between the normal and cancerous tissues. PMID- 26903639 TI - Delay discounting, genetic sensitivity, and leukocyte telomere length. AB - In a graying world, there is an increasing interest in correlates of aging, especially those found in early life. Leukocyte telomere length (LTL) is an emerging marker of aging at the cellular level, but little is known regarding its link with poor decision making that often entails being overly impatient. Here we investigate the relationship between LTL and the degree of impatience, which is measured in the laboratory using an incentivized delay discounting task. In a sample of 1,158 Han Chinese undergraduates, we observe that steeper delay discounting, indexing higher degree of impatience, is negatively associated with LTL. The relationship is robust after controlling for health-related variables, as well as risk attitude-another important determinant of decision making. LTL in females is more sensitive to impatience than in males. We then asked if genes possibly modulate the effect of impatient behavior on LTL. The oxytocin receptor gene (OXTR) polymorphism rs53576, which has figured prominently in investigations of social cognition and psychological resources, and the estrogen receptor beta gene (ESR2) polymorphism rs2978381, one of two gonadal sex hormone genes, significantly mitigate the negative effect of impatience on cellular aging in females. The current results contribute to understanding the relationship between preferences in decision making, particularly impatience, and cellular aging, for the first time to our knowledge. Notably, oxytocin and estrogen receptor polymorphisms temper accelerated cellular aging in young females who tend to make impatient choices. PMID- 26903640 TI - Core disgust is attenuated by ingroup relations. AB - We present the first experimental evidence to our knowledge that ingroup relations attenuate core disgust and that this helps explain the ability of groups to coact. In study 1, 45 student participants smelled a sweaty t-shirt bearing the logo of another university, with either their student identity (ingroup condition), their specific university identity (outgroup condition), or their personal identity (interpersonal condition) made salient. Self-reported disgust was lower in the ingroup condition than in the other conditions, and disgust mediated the relationship between condition and willingness to interact with target. In study 2, 90 student participants smelled a sweaty target t-shirt bearing either the logo of their own university, another university, or no logo, with either their student identity or their specific university identity made salient. Walking time to wash hands and pumps of soap indicated that disgust was lower where the relationship between participant and target was ingroup rather than outgroup or ambivalent (no logo). PMID- 26903641 TI - Brown adipose tissue transplantation ameliorates polycystic ovary syndrome. AB - Polycystic ovary syndrome (PCOS), which is characterized by anovulation, hyperandrogenism, and polycystic ovaries, is a complex endocrinopathy. Because the cause of PCOS at the molecular level is largely unknown, there is no cure or specific treatment for PCOS. Here, we show that transplantation of brown adipose tissue (BAT) reversed anovulation, hyperandrogenism, and polycystic ovaries in a dehydroepiandrosterone (DHEA)-induced PCOS rat. BAT transplantation into a PCOS rat significantly stabilized menstrual irregularity and improved systemic insulin sensitivity up to a normal level, which was not shown in a sham-operated or muscle-transplanted PCOS rat. Moreover, BAT transplantation, not sham operation or muscle transplantation, surprisingly improved fertility in PCOS rats. Interestingly, BAT transplantation activated endogenous BAT and thereby increased the circulating level of adiponectin, which plays a prominent role in whole-body energy metabolism and ovarian physiology. Consistent with BAT transplantation, administration of adiponectin protein dramatically rescued DHEA-induced PCOS phenotypes. These results highlight that endogenous BAT activity is closely related to the development of PCOS phenotypes and that BAT activation might be a promising therapeutic option for the treatment of PCOS. PMID- 26903642 TI - Predictable allele frequency changes due to habitat fragmentation in the Glanville fritillary butterfly. AB - Describing the evolutionary dynamics of now extinct populations is challenging, as their genetic composition before extinction is generally unknown. The Glanville fritillary butterfly has a large extant metapopulation in the Aland Islands in Finland, but declined to extinction in the nearby fragmented southwestern (SW) Finnish archipelago in the 20th century. We genotyped museum samples for 222 SNPs across the genome, including SNPs from candidate genes and neutral regions. SW Finnish populations had significantly reduced genetic diversity before extinction, and their allele frequencies gradually diverged from those in contemporary Aland populations over 80 y. We identified 15 outlier loci among candidate SNPs, mostly related to flight, in which allele frequencies have changed more than the neutral expectation. At outlier loci, allele frequencies in SW Finland shifted in the same direction as newly established populations deviated from old local populations in contemporary Aland. Moreover, outlier allele frequencies in SW Finland resemble those in fragmented landscapes as opposed to continuous landscapes in the Baltic region. These results indicate selection for genotypes associated with good colonization capacity in the highly fragmented landscape before the extinction of the populations. Evolutionary response to habitat fragmentation may have enhanced the viability of the populations, but it did not save the species from regional extinction in the face of severe habitat loss and fragmentation. These results highlight a potentially common situation in changing environments: evolutionary changes are not strong enough to fully compensate for the direct adverse effects of environmental change and thereby rescue populations from extinction. PMID- 26903643 TI - Clocking the social mind by identifying mental processes in the IAT with electrical neuroimaging. AB - Why do people take longer to associate the word "love" with outgroup words (incongruent condition) than with ingroup words (congruent condition)? Despite the widespread use of the implicit association test (IAT), it has remained unclear whether this IAT effect is due to additional mental processes in the incongruent condition, or due to longer duration of the same processes. Here, we addressed this previously insoluble issue by assessing the spatiotemporal evolution of brain electrical activity in 83 participants. From stimulus presentation until response production, we identified seven processes. Crucially, all seven processes occurred in the same temporal sequence in both conditions, but participants needed more time to perform one early occurring process (perceptual processing) and one late occurring process (implementing cognitive control to select the motor response) in the incongruent compared with the congruent condition. We also found that the latter process contributed to individual differences in implicit bias. These results advance understanding of the neural mechanics of response time differences in the IAT: They speak against theories that explain the IAT effect as due to additional processes in the incongruent condition and speak in favor of theories that assume a longer duration of specific processes in the incongruent condition. More broadly, our data analysis approach illustrates the potential of electrical neuroimaging to illuminate the temporal organization of mental processes involved in social cognition. PMID- 26903645 TI - Dynamic Antarctic ice sheet during the early to mid-Miocene. AB - Geological data indicate that there were major variations in Antarctic ice sheet volume and extent during the early to mid-Miocene. Simulating such large-scale changes is problematic because of a strong hysteresis effect, which results in stability once the ice sheets have reached continental size. A relatively narrow range of atmospheric CO2 concentrations indicated by proxy records exacerbates this problem. Here, we are able to simulate large-scale variability of the early to mid-Miocene Antarctic ice sheet because of three developments in our modeling approach. (i) We use a climate-ice sheet coupling method utilizing a high resolution atmospheric component to account for ice sheet-climate feedbacks. (ii) The ice sheet model includes recently proposed mechanisms for retreat into deep subglacial basins caused by ice-cliff failure and ice-shelf hydrofracture. (iii) We account for changes in the oxygen isotopic composition of the ice sheet by using isotope-enabled climate and ice sheet models. We compare our modeling results with ice-proximal records emerging from a sedimentological drill core from the Ross Sea (Andrill-2A) that is presented in a companion article. The variability in Antarctic ice volume that we simulate is equivalent to a seawater oxygen isotope signal of 0.52-0.660/00, or a sea level equivalent change of 30-36 m, for a range of atmospheric CO2 between 280 and 500 ppm and a changing astronomical configuration. This result represents a substantial advance in resolving the long-standing model data conflict of Miocene Antarctic ice sheet and sea level variability. PMID- 26903644 TI - Antarctic ice sheet sensitivity to atmospheric CO2 variations in the early to mid Miocene. AB - Geological records from the Antarctic margin offer direct evidence of environmental variability at high southern latitudes and provide insight regarding ice sheet sensitivity to past climate change. The early to mid-Miocene (23-14 Mya) is a compelling interval to study as global temperatures and atmospheric CO2 concentrations were similar to those projected for coming centuries. Importantly, this time interval includes the Miocene Climatic Optimum, a period of global warmth during which average surface temperatures were 3-4 degrees C higher than today. Miocene sediments in the ANDRILL-2A drill core from the Western Ross Sea, Antarctica, indicate that the Antarctic ice sheet (AIS) was highly variable through this key time interval. A multiproxy dataset derived from the core identifies four distinct environmental motifs based on changes in sedimentary facies, fossil assemblages, geochemistry, and paleotemperature. Four major disconformities in the drill core coincide with regional seismic discontinuities and reflect transient expansion of grounded ice across the Ross Sea. They correlate with major positive shifts in benthic oxygen isotope records and generally coincide with intervals when atmospheric CO2 concentrations were at or below preindustrial levels (~280 ppm). Five intervals reflect ice sheet minima and air temperatures warm enough for substantial ice mass loss during episodes of high (~500 ppm) atmospheric CO2 These new drill core data and associated ice sheet modeling experiments indicate that polar climate and the AIS were highly sensitive to relatively small changes in atmospheric CO2 during the early to mid Miocene. PMID- 26903646 TI - Dietary options and behavior suggested by plant biomarker evidence in an early human habitat. AB - The availability of plants and freshwater shapes the diets and social behavior of chimpanzees, our closest living relative. However, limited evidence about the spatial relationships shared between ancestral human (hominin) remains, edible resources, refuge, and freshwater leaves the influence of local resources on our species' evolution open to debate. Exceptionally well-preserved organic geochemical fossils--biomarkers--preserved in a soil horizon resolve different plant communities at meter scales across a contiguous 25,000 m(2) archaeological land surface at Olduvai Gorge from about 2 Ma. Biomarkers reveal hominins had access to aquatic plants and protective woods in a patchwork landscape, which included a spring-fed wetland near a woodland that both were surrounded by open grassland. Numerous cut-marked animal bones are located within the wooded area, and within meters of wetland vegetation delineated by biomarkers for ferns and sedges. Taken together, plant biomarkers, clustered bone debris, and hominin remains define a clear spatial pattern that places animal butchery amid the refuge of an isolated forest patch and near freshwater with diverse edible resources. PMID- 26903648 TI - Future sea level rise constrained by observations and long-term commitment. AB - Sea level has been steadily rising over the past century, predominantly due to anthropogenic climate change. The rate of sea level rise will keep increasing with continued global warming, and, even if temperatures are stabilized through the phasing out of greenhouse gas emissions, sea level is still expected to rise for centuries. This will affect coastal areas worldwide, and robust projections are needed to assess mitigation options and guide adaptation measures. Here we combine the equilibrium response of the main sea level rise contributions with their last century's observed contribution to constrain projections of future sea level rise. Our model is calibrated to a set of observations for each contribution, and the observational and climate uncertainties are combined to produce uncertainty ranges for 21st century sea level rise. We project anthropogenic sea level rise of 28-56 cm, 37-77 cm, and 57-131 cm in 2100 for the greenhouse gas concentration scenarios RCP26, RCP45, and RCP85, respectively. Our uncertainty ranges for total sea level rise overlap with the process-based estimates of the Intergovernmental Panel on Climate Change. The "constrained extrapolation" approach generalizes earlier global semiempirical models and may therefore lead to a better understanding of the discrepancies with process-based projections. PMID- 26903647 TI - Leptin signaling regulates glucose homeostasis, but not adipostasis, in the zebrafish. AB - Leptin is the primary adipostatic factor in mammals. Produced largely by adipocytes in proportion to total adipose mass, the hormone informs the brain regarding total energy stored as triglycerides in fat cells. The hormone acts on multiple circuits in the brain to regulate food intake, autonomic outflow, and endocrine function to maintain energy balance. In addition to regulating adipose mass, mammalian leptin also plays a role in the regulation of glucose homeostasis and as a gating factor in reproductive competence. Leptin-deficient mice and people exhibit early onset profound hyperphagia and obesity, diabetes, and infertility. Although leptin and the leptin receptor are found in fish, the hormone is not expressed in adipose tissue, but is found in liver and other tissues. Here, we show that adult zebrafish lacking a functional leptin receptor do not exhibit hyperphagia or increased adiposity, and exhibit normal fertility. However, leptin receptor-deficient larvae have increased numbers of beta-cells and increased levels of insulin mRNA. Furthermore, larval zebrafish have been shown to exhibit beta-cell hyperplasia in response to high fat feeding or peripheral insulin resistance, and we show here that leptin receptor is required for this response. Adult zebrafish also have increased levels of insulin mRNA and other alterations in glucose homeostasis. Thus, a role for leptin in the regulation of beta-cell mass and glucose homeostasis appears to be conserved across vertebrates, whereas its role as an adipostatic factor is likely to be a secondary role acquired during the evolution of mammals. PMID- 26903649 TI - Shame closely tracks the threat of devaluation by others, even across cultures. AB - We test the theory that shame evolved as a defense against being devalued by others. By hypothesis, shame is a neurocomputational program tailored by selection to orchestrate cognition, motivation, physiology, and behavior in the service of: (i) deterring the individual from making choices where the prospective costs of devaluation exceed the benefits, (ii) preventing negative information about the self from reaching others, and (iii) minimizing the adverse effects of devaluation when it occurs. Because the unnecessary activation of a defense is costly, the shame system should estimate the magnitude of the devaluative threat and use those estimates to cost-effectively calibrate its activation: Traits or actions that elicit more negative evaluations from others should elicit more shame. As predicted, shame closely tracks the threat of devaluation in the United States (r = .69), India (r = .79), and Israel (r = .67). Moreover, shame in each country strongly tracks devaluation in the others, suggesting that shame and devaluation are informed by a common species-wide logic of social valuation. The shame-devaluation link is also specific: Sadness and anxiety-emotions that coactivate with shame-fail to track devaluation. To our knowledge, this constitutes the first empirical demonstration of a close, specific match between shame and devaluation within and across cultures. PMID- 26903650 TI - Ultrafast energy relaxation in single light-harvesting complexes. AB - Energy relaxation in light-harvesting complexes has been extensively studied by various ultrafast spectroscopic techniques, the fastest processes being in the sub-100-fs range. At the same time, much slower dynamics have been observed in individual complexes by single-molecule fluorescence spectroscopy (SMS). In this work, we use a pump-probe-type SMS technique to observe the ultrafast energy relaxation in single light-harvesting complexes LH2 of purple bacteria. After excitation at 800 nm, the measured relaxation time distribution of multiple complexes has a peak at 95 fs and is asymmetric, with a tail at slower relaxation times. When tuning the excitation wavelength, the distribution changes in both its shape and position. The observed behavior agrees with what is to be expected from the LH2 excited states structure. As we show by a Redfield theory calculation of the relaxation times, the distribution shape corresponds to the expected effect of Gaussian disorder of the pigment transition energies. By repeatedly measuring few individual complexes for minutes, we find that complexes sample the relaxation time distribution on a timescale of seconds. Furthermore, by comparing the distribution from a single long-lived complex with the whole ensemble, we demonstrate that, regarding the relaxation times, the ensemble can be considered ergodic. Our findings thus agree with the commonly used notion of an ensemble of identical LH2 complexes experiencing slow random fluctuations. PMID- 26903651 TI - Profile of Dan Littman, winner of the 2016 Vilcek Prize in Biomedical Science. PMID- 26903652 TI - ER stress stimulates production of the key antimicrobial peptide, cathelicidin, by forming a previously unidentified intracellular S1P signaling complex. AB - We recently identified a previously unidentified sphingosine-1-phosphate (S1P) signaling mechanism that stimulates production of a key innate immune element, cathelicidin antimicrobial peptide (CAMP), in mammalian cells exposed to external perturbations, such as UVB irradiation and other oxidative stressors that provoke subapoptotic levels of endoplasmic reticulum (ER) stress, independent of the well known vitamin D receptor-dependent mechanism. ER stress increases cellular ceramide and one of its distal metabolites, S1P, which activates NF-kappaB followed by C/EBPalpha activation, leading to CAMP production, but in a S1P receptor-independent fashion. We now show that S1P activates NF-kappaB through formation of a previously unidentified signaling complex, consisting of S1P, TRAF2, and RIP1 that further associates with three stress-responsive proteins; i.e., heat shock proteins (GRP94 and HSP90alpha) and IRE1alpha. S1P specifically interacts with the N-terminal domain of heat shock proteins. Because this ER stress-initiated mechanism is operative in both epithelial cells and macrophages, it appears to be a universal, highly conserved response, broadly protective against diverse external perturbations that lead to increased ER stress. Finally, these studies further illuminate how ER stress and S1P orchestrate critical stress-specific signals that regulate production of one protective response by stimulating production of the key innate immune element, CAMP. PMID- 26903653 TI - Rehabilitation drives enhancement of neuronal structure in functionally relevant neuronal subsets. AB - We determined whether rehabilitation after cortical injury also drives dynamic dendritic and spine changes in functionally distinct subsets of neurons, resulting in functional recovery. Moreover, given known requirements for cholinergic systems in mediating complex forms of cortical plasticity, including skilled motor learning, we hypothesized that cholinergic systems are essential mediators of neuronal structural and functional plasticity associated with motor rehabilitation. Adult rats learned a skilled forelimb grasping task and then, underwent destructive lesions of the caudal forelimb region of the motor cortex, resulting in nearly complete loss of grasping ability. Subsequent intensive rehabilitation significantly enhanced both dendritic architecture and spine number in the adjoining rostral forelimb area compared with that in the lesioned animals that were not rehabilitated. Cholinergic ablation markedly attenuated rehabilitation-induced recovery in both neuronal structure and motor function. Thus, rehabilitation focused on an affected limb robustly drives structural compensation in perilesion cortex, enabling functional recovery. PMID- 26903654 TI - Inability to suppress salient distractors predicts low visual working memory capacity. AB - According to contemporary accounts of visual working memory (vWM), the ability to efficiently filter relevant from irrelevant information contributes to an individual's overall vWM capacity. Although there is mounting evidence for this hypothesis, very little is known about the precise filtering mechanism responsible for controlling access to vWM and for differentiating low- and high capacity individuals. Theoretically, the inefficient filtering observed in low capacity individuals might be specifically linked to problems enhancing relevant items, suppressing irrelevant items, or both. To find out, we recorded neurophysiological activity associated with attentional selection and active suppression during a competitive visual search task. We show that high-capacity individuals actively suppress salient distractors, whereas low-capacity individuals are unable to suppress salient distractors in time to prevent those items from capturing attention. These results demonstrate that individual differences in vWM capacity are associated with the timing of a specific attentional control operation that suppresses processing of salient but irrelevant visual objects and restricts their access to higher stages of visual processing. PMID- 26903655 TI - Contraction of the type I IFN locus and unusual constitutive expression of IFN alpha in bats. AB - Bats harbor many emerging and reemerging viruses, several of which are highly pathogenic in other mammals but cause no clinical signs of disease in bats. To determine the role of interferons (IFNs) in the ability of bats to coexist with viruses, we sequenced the type I IFN locus of the Australian black flying fox, Pteropus alecto, providing what is, to our knowledge, the first gene map of the IFN region of any bat species. Our results reveal a highly contracted type I IFN family consisting of only 10 IFNs, including three functional IFN-alpha loci. Furthermore, the three IFN-alpha genes are constitutively expressed in unstimulated bat tissues and cells and their expression is unaffected by viral infection. Constitutively expressed IFN-alpha results in the induction of a subset of IFN-stimulated genes associated with antiviral activity and resistance to DNA damage, providing evidence for a unique IFN system that may be linked to the ability of bats to coexist with viruses. PMID- 26903656 TI - Rare recombination events generate sequence diversity among balancer chromosomes in Drosophila melanogaster. AB - Multiply inverted balancer chromosomes that suppress exchange with their homologs are an essential part of the Drosophila melanogaster genetic toolkit. Despite their widespread use, the organization of balancer chromosomes has not been characterized at the molecular level, and the degree of sequence variation among copies of balancer chromosomes is unknown. To map inversion breakpoints and study potential diversity in descendants of a structurally identical balancer chromosome, we sequenced a panel of laboratory stocks containing the most widely used X chromosome balancer, First Multiple 7 (FM7). We mapped the locations of FM7 breakpoints to precise euchromatic coordinates and identified the flanking sequence of breakpoints in heterochromatic regions. Analysis of SNP variation revealed megabase-scale blocks of sequence divergence among currently used FM7 stocks. We present evidence that this divergence arose through rare double crossover events that replaced a female-sterile allele of the singed gene (sn(X2)) on FM7c with a sequence from balanced chromosomes. We propose that although double-crossover events are rare in individual crosses, many FM7c chromosomes in the Bloomington Drosophila Stock Center have lost sn(X2) by this mechanism on a historical timescale. Finally, we characterize the original allele of the Bar gene (B(1)) that is carried on FM7, and validate the hypothesis that the origin and subsequent reversion of the B(1) duplication are mediated by unequal exchange. Our results reject a simple nonrecombining, clonal mode for the laboratory evolution of balancer chromosomes and have implications for how balancer chromosomes should be used in the design and interpretation of genetic experiments in Drosophila. PMID- 26903657 TI - Driver crash risk factors and prevalence evaluation using naturalistic driving data. AB - The accurate evaluation of crash causal factors can provide fundamental information for effective transportation policy, vehicle design, and driver education. Naturalistic driving (ND) data collected with multiple onboard video cameras and sensors provide a unique opportunity to evaluate risk factors during the seconds leading up to a crash. This paper uses a National Academy of Sciences sponsored ND dataset comprising 905 injurious and property damage crash events, the magnitude of which allows the first direct analysis (to our knowledge) of causal factors using crashes only. The results show that crash causation has shifted dramatically in recent years, with driver-related factors (i.e., error, impairment, fatigue, and distraction) present in almost 90% of crashes. The results also definitively show that distraction is detrimental to driver safety, with handheld electronic devices having high use rates and risk. PMID- 26903658 TI - Contact inhibition of locomotion determines cell-cell and cell-substrate forces in tissues. AB - Cells organized in tissues exert forces on their neighbors and their environment. Those cellular forces determine tissue homeostasis as well as reorganization during embryonic development and wound healing. To understand how cellular forces are generated and how they can influence the tissue state, we develop a particle based simulation model for adhesive cell clusters and monolayers. Cells are contractile, exert forces on their substrate and on each other, and interact through contact inhibition of locomotion (CIL), meaning that cell-cell contacts suppress force transduction to the substrate and propulsion forces align away from neighbors. Our model captures the traction force patterns of small clusters of nonmotile cells and larger sheets of motile Madin-Darby canine kidney (MDCK) cells. In agreement with observations in a spreading MDCK colony, the cell density in the center increases as cells divide and the tissue grows. A feedback between cell density, CIL, and cell-cell adhesion gives rise to a linear relationship between cell density and intercellular tensile stress and forces the tissue into a nonmotile state characterized by a broad distribution of traction forces. Our model also captures the experimentally observed tissue flow around circular obstacles, and CIL accounts for traction forces at the edge. PMID- 26903659 TI - Temperature-driven global sea-level variability in the Common Era. AB - We assess the relationship between temperature and global sea-level (GSL) variability over the Common Era through a statistical metaanalysis of proxy relative sea-level reconstructions and tide-gauge data. GSL rose at 0.1 +/- 0.1 mm/y (2sigma) over 0-700 CE. A GSL fall of 0.2 +/- 0.2 mm/y over 1000-1400 CE is associated with ~ 0.2 degrees C global mean cooling. A significant GSL acceleration began in the 19th century and yielded a 20th century rise that is extremely likely (probability [Formula: see text]) faster than during any of the previous 27 centuries. A semiempirical model calibrated against the GSL reconstruction indicates that, in the absence of anthropogenic climate change, it is extremely likely ([Formula: see text]) that 20th century GSL would have risen by less than 51% of the observed [Formula: see text] cm. The new semiempirical model largely reconciles previous differences between semiempirical 21st century GSL projections and the process model-based projections summarized in the Intergovernmental Panel on Climate Change's Fifth Assessment Report. PMID- 26903660 TI - Evaluation of Parotid Glands With Real-time Ultrasound Elastography in Children. AB - OBJECTIVES: The aim of this study was to determine the strain index for parotid glands in children by using ultrasound elastography. METHODS: In this prospective study, apparently healthy children were referred from the ear-nose-throat clinic to the radiology clinic for elastographic examinations. Conventional sonographic and elastographic examinations of the parotid glands were performed. A linear 5 12-MHz transducer was used to obtain the images. RESULTS: A total of 54 children were enrolled in this prospective study. The normal mean strain index value +/- SD for the parotid glands was 1.24 +/- 0.67 (range, 0.29-1.39) regardless of sex. The mean age of girls was 7.42 +/- 2.94 years (range, 3-14 years), and the age of boys was 8.50 +/- 3.46 years (range, 4-16 years). The strain index values for the parotid glands in boys was 1.25 +/- 0.76, and in girls it was 1.22 +/- 0.55. There was no statistically significant difference in the strain index values between girls and boys (P= .986). There was no correlation between the strain index and age (r = 0.026) or body mass index (r = 0.066). CONCLUSIONS: This study determined the mean strain index values for apparently healthy children. Such information can serve as a baseline from which pathologic parotid diseases can be diagnosed with ultrasound elastography in combination with other sonographic criteria. PMID- 26903662 TI - Intraductal Sonography in Patients With Portal Cavernoma Cholangiopathy. AB - Intraductal sonography generates high-resolution images of the entire length of the biliary tree and peribiliary tissues, including 3-dimensional dual- and muti plane reconstructions to depict complex anatomy. Portal cavernoma cholangiopathy (previously called portal biliopathy) can have multiple etiologies of obstructive cholestasis in the same patient, which can be difficult to define even with advanced imaging techniques.We describe 2 difficult cases of portal cavernoma cholangiopathy in which intraductal sonography helped in clinical management decisions. We think that intraductal sonography should be part of the standard management algorithm for patients with portal cavernoma cholangiopathy and describe the intraductal sonographic correlates of the cholangiographic changes in this condition. PMID- 26903661 TI - Clinical Importance and Natural History of Biliary Sludge in Outpatients. AB - OBJECTIVES: Gallbladder sludge is a common diagnosis on routine abdominal sonography, yet its clinical importance is uncertain, especially in outpatients. To determine its natural history and potential future complications in this setting, we reviewed the imaging and clinical histories of nonhospitalized patients with a diagnosis of sludge on sonography. METHODS: We conducted a retrospective search of our institutional radiology information system for all sonographic reports using the key words "biliary sludge without gallstones" over a 3-year period. For each of the 104 patients with isolated biliary sludge on initial sonography, we reviewed the electronic medical records and all imaging for the development of pancreaticobiliary complications. RESULTS: We found an overall prevalence of biliary sludge in outpatients of 1.8%. Of the 104 patients reviewed with a mean follow up of 630 days (21 months), 25 developed a pancreaticobiliary complication, including cholelithiasis, cholecystitis, choledocholithiasis, and pancreatitis. The most frequent complication was cholecystitis, with a total of 14 diagnoses (12 chronic acalculous and 2 acute with gallstones). An additional 6 patients developed gallstones without cholecystitis features; 4 patients developed pancreatitis; and 1 developed choledocholithiasis. Biliary sludge remained quiescent or resolved in 76% of patients. CONCLUSIONS: Biliary sludge always represents a pathologic process, but its clinical implications among outpatients have not been previously investigated. Our ambulatory population developed pancreaticobiliary complications at similar rates as prior mixed-patient setting studies. Regardless of the patient setting, biliary sludge is likely of more clinical importance than previously regarded. PMID- 26903663 TI - Management of children with type 1 diabetes during illness: a national survey. AB - AIM: Adequate sick-day management at home can reduce the risk of progression to diabetic ketoacidosis and admission to hospital. The aim of this project was to review the management of diabetes during illness. METHOD: The Association of Children's Diabetes Clinicians (ACDC) carried out a questionnaire survey of all paediatric diabetes units. In addition, parents of children with type 1 diabetes completed an online questionnaire. RESULTS: The survey of 127 units had a 73% response rate. Sick-day management guidelines were in place in 93%. All guidelines advised giving extra insulin during illness. In 67%, the extra dose was based on a fraction of total daily dose. 22% used units per kg body weight (U/kg). 21% used locally derived formulae to calculate extra dose of insulin. 3% of units advised only blood ketone monitoring. Although all units had an out-of hours access policy for the families, 45% received advice from the general paediatric registrar. Only in 15%, the advice was directly from a member of the paediatric diabetes team. 680 parents completed the questionnaire. 86% reported receiving training on managing sick days. The majority (52.2%) receiving an informal session at diagnosis. 40% did not know what to do in the presence of raised blood glucose and high blood ketones. CONCLUSIONS: There was a wide variation in the practice of monitoring and advice given during illness. Both surveys highlight need for national guidance as well and to improve quality of sick-day rule education programmes for parents of children with type 1 diabetes. PMID- 26903664 TI - Self-reported preparedness for clinical work has increased among recent cohorts of UK-trained first-year doctors. AB - INTRODUCTION: UK medical schools have made considerable efforts to ensure that graduates are well prepared for their first year of clinical work. We report the views of two recent cohorts of UK-trained doctors 1 year after graduation about whether their medical school prepared them well, and compare responses with earlier cohorts. METHODS: We surveyed doctors who qualified in 2011 and 2012 from all UK medical schools. We obtained their responses to the statement 'My experience at medical school prepared me well for the jobs I have undertaken so far' on a 5-point scale from 'Strongly Agree' to 'Strongly Disagree'. Responses were compared with those of the UK graduates of 1999, 2000, 2002, 2005, 2008 and 2009, surveyed in the same way 1 year after graduation. RESULTS: The percentage of doctors who either 'Agreed' or 'Strongly Agreed' that they were well prepared doubled from 35% in 1999 to 70% in 2012, while the percentage who 'Strongly Agreed' with the statement increased fourfold. Perceptions of being well prepared have increased in graduates from almost every medical school. Variation between medical schools in self-reported preparedness of their graduates has decreased in recent cohorts. However, some large differences between medical schools remain. Significant differences in perceived preparedness remain between white and non white doctors, but have diminished between men and women. CONCLUSIONS: Our work contributes to growing evidence suggesting that changes to medical education in the UK are producing doctors who feel well prepared for the challenges of being a doctor, though further improvements could be made. PMID- 26903665 TI - Correction. PMID- 26903667 TI - Off-label use of drugs: An evil or a necessity? PMID- 26903666 TI - Diagnostic Measures for the Cox Regression Model with Missing Covariates. AB - This paper investigates diagnostic measures for assessing the influence of observations and model misspecification in the presence of missing covariate data for the Cox regression model. Our diagnostics include case-deletion measures, conditional martingale residuals, and score residuals. The Q-distance is proposed to examine the effects of deleting individual observations on the estimates of finite-dimensional and infinite-dimensional parameters. Conditional martingale residuals are used to construct goodness of fit statistics for testing possible misspecification of the model assumptions. A resampling method is developed to approximate the p-values of the goodness of fit statistics. Simulation studies are conducted to evaluate our methods, and a real data set is analyzed to illustrate their use. PMID- 26903668 TI - Does non-medical grade power cord compromise the safety of medical equipment? AB - A tertiary care 1000 bedded hospital contains more than 10,000 pieces of equipment worth approximately 41 million USD, while the power cords supplied along with the imported equipment do not comply with country-specific norms. Moreover, the local vendors procure power cords with type D/M plug to complete installation and also on-site electrical safety test is not performed. Hence, this project was undertaken to evaluate the electrical safety of all life-saving equipment purchased in the year 2013, referring to the guidelines of International Electrotechnical Commission 62353, the Association for the Advancement of Medical Instrumentation (AAMI) and National Fire Protection Association (NFPA)-99 hospital standard for the analysis of protective earth resistance and chassis leakage current. This study was done with a measuring device namely electrical safety analyser 612 model from Fluke Biomedical. PMID- 26903669 TI - A comparative study of effect of sevoflurane on intubating conditions with rocuronium in neurosurgical patients. AB - BACKGROUND AND AIMS: Rocuronium may not always be the preferred relaxant for rapid sequence intubation. When 2% sevoflurane is used in conjunction with rocuronium, it may reduce the time required for achieving complete skeletal muscle relaxation with the intubating dose of rocuronium. METHODS: This study was prospective, randomised, double-blind in nature and compared the effect of sevoflurane on intubation time and intubating conditions when used along with rocuronium. Thirty adult patients belonging to American Society of Anesthesiologists physical status Grades 1 and 2, of either gender aged between 30 and 65 years undergoing neurosurgical operations were randomly allocated into two equal groups: Group R received 0.8 mg/kg rocuronium, and Group RS received 0.8 mg/kg of rocuronium with 2% sevoflurane. Onset time of intubation was assessed using train-of-four stimuli. The intubating conditions were compared using the Cooper scoring system and the haemodynamic responses were compared between the two groups. RESULTS: The onset time of intubation was 101.73 +/- 10.28 s in Group R and 60.4 +/- 4.1 s in Group RS (P < 0.001), with excellent intubating conditions in both groups and without any adverse effects. Significant differences in heart rate and mean arterial pressure were seen immediately after intubation, at 1 and 3 min (P < 0.05) between the two groups. CONCLUSION: Rocuronium 0.8 mg/kg along with 2% sevoflurane provides excellent intubating conditions within 60-66 s from its administration. PMID- 26903671 TI - Comparison between intravenous dexmedetomidine and local lignocaine infiltration to attenuate the haemodynamic response to skull pin head holder application during craniotomy. AB - BACKGROUND AND AIMS: Skull pin application is intensely painful and can be accompanied by detrimental haemodynamic changes. We compared intravenous (IV) dexmedetomidine with local infiltration of lignocaine at pin application sites to attenuate haemodynamic changes associated with pin application. METHODS: Fifty two patients undergoing craniotomy were randomised to either group dexmedetomidine (received 1 MUg/kg dexmedetomidine over 10 min starting at induction of anaesthesia) or group lignocaine (received 3 ml of 2% lignocaine infiltration at pin application sites before pin application). Anaesthetic protocol was standardised. Heart rate (HR) and mean arterial pressure (MAP) were recorded at the following time intervals, pre-induction baseline, pre infiltration, post-infiltration, pre-pin application and post-pin application at 1, 2, 3, 4, 5, 10 and 15 min. Statistical analysis was done using independent samples t-test, Fisher exact test and Chi-square test. RESULTS: HR and MAP were comparable between the groups at all the study intervals. The incidence of adverse haemodynamic effects attributable to pin application (tachycardia and/or hypertension) was comparable between the groups (2 patients in group dexmedetomidine and 5 in group lignocaine). However, the incidence of hypotension and/or bradycardia was significantly greater in the dexmedetomidine group (19 patients in group dexmedetomidine and 5 patients in group lignocaine; P = 0.0007). CONCLUSION: IV dexmedetomidine 1 mcg/kg over 10 min is comparable to local infiltration of 2% lignocaine at pin application sites to attenuate the haemodynamic response associated with skull pin application. However, use of dexmedetomidine is associated with significantly higher incidence of hypotension and bradycardia. PMID- 26903670 TI - Does labour epidural slow the progress of labour and lead to complications? Obstetricians' perception working in private and public sector teaching hospitals in a developing country. AB - BACKGROUND AND AIMS: Obstetricians play a major role in the decision making for provision of analgesia for the woman in labour. As epidural analgesia (EA) is the most preferred technique, it is important to know obstetricians' perception regarding its effect on progress of labour and associated complications. METHODS: The 6 months cross-sectional study included 114 obstetricians from teaching hospitals. After informed consent, obstetricians were asked to fill a predesigned questionnaire containing 13 close ended questions regarding their perception on the effect of EA on progress of labour, EA complications and whether they would recommend EA to their patients or not. Other variables included age, gender, training in EA, practice type and hospital settings (private or public sector). RESULTS: Majority of the obstetricians had the perception of EA prolonging the first stage (89.5%) and second stage (98.2%) of labour, increasing the rate of caesarean section (87.7%), instrumental delivery (58.8%) and increasing the incidence of backache (85.5%). None of the obstetricians received any formal training in EA. Majority (84.2%) were not sure if they would recommend EA to their patients. When these responses were compared between public and private sector, a statistically higher percentage (P < 0.001) of public sector obstetricians had negative perception of EA. CONCLUSION: Perception of obstetrician regarding EA is contrary to the current evidence. There is a need to introduce formal curriculum on EA in obstetric training program and conduct regular refresher courses. PMID- 26903672 TI - Incident reporting in post-operative patients managed by acute pain service. AB - BACKGROUND AND AIMS: Incident reporting is a reliable and inexpensive tool used in anaesthesia to identify errors in patient management. A hospital incident reporting system was already present in our hospital, but we were unable to find any incident related to acute pain management. Hence, acute pain service (APS) was started for voluntary incident reporting in post-operative patients to identify critical incidents, review the root cause and suggest remedial measures. METHODS: All post-operative patients managed by APS were included in this observational study. A proforma was developed by APS, which included information about the type of incident (equipment and patient-related, human errors), severity of incident, person responsible and suggestions to prevent the same incident in the future. Patients and medical staff were informed about the reporting system. Whenever an incident was identified, a proforma was filled out by APS resident and data entered in SPSS programme. RESULTS: Total of 98 (1.80%) incidents were reported in 5432 patients managed by APS during 3 years period. Average age of the patients was 46 +/- 17 years. Majority of incidents were related to epidural care (71%) and occurred in surgical wards (87%). Most of the incidents occurred due to human error and infusion delivery set-related defects. CONCLUSION: Incident reporting proved to be a feasible method of improving quality care in developing countries. It not only provides valuable information about areas which needed improvement, but also helped in developing strategies to improve care. Knowledge and attitudes of medical and paramedical staff are identified as the targeted area for improvement. PMID- 26903673 TI - Current views and practice of faculty members and consultants regarding 'Publications in India': A cross-sectional study. AB - BACKGROUND AND AIMS: There is an increasing enthusiasm and pressure to submit scientific articles to journals for publication due to official policies. This has led to increased stress on authors and editors and in issues like plagiarism. We planned a cross-sectional study with an aim to explore the current publication related views and practice of faculty members and consultants. METHODS: We conducted a questionnaire based prospective survey with 22 questions divided into parts. Print and electronic versions were sent to around 18,270 members in total, a majority of whom were anaesthesiologists and 600 members responded to our questionnaire. A database was created and analysed using Microsoft Excel. RESULTS: About 80% felt that online journals were better read than print journals. Eighty eight percent agreed that publications improve academic skills. The Medical Council of India requirements to publish in reputed journals were cited as the main reasons for plagiarism. The publication rule had become a burden for 46% respondents. Review articles were most likely to be read though clinical investigations were considered to be of maximum academic significance. Review/publishing time followed by author requirements and journal indexing were the points our respondents liked to see most when choosing a journal for article submission. CONCLUSION: Our survey results depict the current author related views and trends in publication practice which may guide in evidence-based policy making. PMID- 26903675 TI - Anaesthetic management of extra-pleural pneumonectomy and hyperthermic intrathoracic chemotherapy procedure. AB - Malignant pleural mesothelioma is a rare tumour with survival of 9-17 months after diagnosis. Radical surgical resection by extra-pleural pneumonectomy combined with hyperthermic intrathoracic chemotherapy has shown to improve patient survival and better microscopic tumour control. Anaesthetic management of this procedure is challenging due to the complex pathophysiological changes associated with prolonged duration of surgery, one- lung ventilation, haemodynamic instability due to major blood loss, temperature variations including heat loss during pneumonectomy and rapid rise in temperature during hyperthermic chemotherapy, cardiac arrhythmias due to exposure to heated chemotherapeutics, cisplatin toxicity and acid-base changes. Intra-operative management involves protective ventilation, regulation of temperature and haemodynamics along with prevention of complications associated with 'heated chemotherapeutics'. Thorough pre-operative assessment and preparation, advanced intra-operative monitoring with prompt corrective interventions, will help in improved patient outcome in the immediate post-operative period. We present one such case done for the 1(st) time in India. PMID- 26903674 TI - Current practice of difficult airway management: A survey. AB - BACKGROUND AND AIMS: Difficult airway (DA) management depends on both training and actual usage of the various approaches in the event of difficulty. The aim of the study was to assess how well the anaesthesiologists are equipped to deal with DA situations. The current practice preference of DA management was also assessed. METHODS: A questionnaire was distributed in a continuing medical education (CME) programme dedicated to DA and responses were noted and analysed, using Statistical Package for Social Sciences (SPSS) version 18. RESULTS: The response rate was 73%. Airway assessment was performed by majority. Sixty eight percent consultants and 47% residents were well aware of the American Society of Anesthesiologists' DA algorithm. 67% consultants and 65% residents attended at least one CME on DA in the previous 5 years. There was an overall deficiency of video laryngoscopes, retrograde intubation and cricothyrotomy sets. Most of the respondents were comfortable in using supraglottic airway devices (SGADs). In anticipated DA, the preferred choice of management for junior doctors was attempting conventional method once and awake fibreoptic bronchoscopy (FOB) for the experienced. In unanticipated DA, most of the residents and consultants opted for SGAD. Extubation strategy was similar for both. Thirty four percent of respondents experienced a 'cannot intubate-cannot ventilate' situation at least once. CONCLUSION: Our survey showed that most respondents performed routine pre operative airway assessment. A good armamentarium of airway gadgets should be made available in hospitals. Further training in techniques like video laryngoscopy, FOB or cricothyrotomy are essential. PMID- 26903676 TI - Perioperative management of patient with Bombay blood group undergoing mitral valve replacement. AB - Bombay red blood cell phenotype is an extremely rare blood type for which patients can receive only autologous or Bombay phenotype red blood cells. We report a case of stenotic mitral valve with Bombay phenotype who underwent minimal invasive right lateral thoracotomy for the replacement of the mitral valve. A male patient from Bangladesh presented to the hospital with New York Heart Association III symptoms. His medical evaluation revealed severe mitral valve stenosis and mild aortic valve regurgitation. The patient received erythropoietin, intravenous iron succinate and folic acid tablets. Autologous blood transfusion was carried out. The mitral valve was replaced with a prosthetic valve successfully. After weaning off from cardiopulmonary bypass, heparinisation was corrected with protamine. Post-operatively, the patient received autologous red blood cells. The patient recovered after 1-day of inotropic support with adrenaline and milrinone, and diuretics and was discharged on the 5(th) post-operative day. PMID- 26903677 TI - Peripherally inserted central venous catheter line removal leading to brachial vein stripping- Need for more caution. PMID- 26903678 TI - Perioperative anaesthetic management of phaeochromocytoma associated with uncorrected tetralogy of Fallot. PMID- 26903679 TI - Anaesthetic management of bilateral hand transplantation. PMID- 26903680 TI - Thoracic spinal cord stimulation for low back pain in a patient with permanent pacemaker. PMID- 26903681 TI - Ultrasound guided brachial block in a case of brachial plexus hypertrophy. PMID- 26903682 TI - A simple test of baricity for subarachnoid drugs. PMID- 26903683 TI - Spurious oxygen saturation value: A dilemma for anaesthesiologist. PMID- 26903684 TI - Gum elastic bougie as a tube exchanger: Modified technique. PMID- 26903685 TI - Insulin IP Calc: A smartphone application for insulin infusion protocol in Intensive Care Units. PMID- 26903686 TI - Aluminium phosphide poisoning: Need for revised treatment guidelines. PMID- 26903687 TI - Reinforcement Learning Trees. AB - In this paper, we introduce a new type of tree-based method, reinforcement learning trees (RLT), which exhibits significantly improved performance over traditional methods such as random forests (Breiman, 2001) under high-dimensional settings. The innovations are three-fold. First, the new method implements reinforcement learning at each selection of a splitting variable during the tree construction processes. By splitting on the variable that brings the greatest future improvement in later splits, rather than choosing the one with largest marginal effect from the immediate split, the constructed tree utilizes the available samples in a more efficient way. Moreover, such an approach enables linear combination cuts at little extra computational cost. Second, we propose a variable muting procedure that progressively eliminates noise variables during the construction of each individual tree. The muting procedure also takes advantage of reinforcement learning and prevents noise variables from being considered in the search for splitting rules, so that towards terminal nodes, where the sample size is small, the splitting rules are still constructed from only strong variables. Last, we investigate asymptotic properties of the proposed method under basic assumptions and discuss rationale in general settings. PMID- 26903688 TI - PARENTING IN ADOLESCENCE AND YOUNG ADULT INTIMATE PARTNER VIOLENCE. AB - Most prior studies of intimate partner violence (IPV) have relied on traditional indices of parental support, control or coercion to examine the nature and extent of parental influences. We explore whether parents' more general attitudes toward their child's dating and associated parenting practices are related to the young adult child's report of IPV, once traditional parent factors and other covariates are introduced. Using data from the Toledo Adolescent Relationships Study (n = 625), results indicate that net of other parenting dimensions and controls for child and neighborhood characteristics, parental negativity about their child's dating and related parenting practices are associated with later reports of IPV during young adulthood. Parent-child conflict and the child's own feelings of gender mistrust were considered as potential mediators. Results suggest the importance of widening the lens beyond support, control and even the parents' own use of violence to include a range of parental attitudes and behaviors that influence the child's approach to and conduct within the romantic realm. PMID- 26903689 TI - Increased Umbilical Cord PAI-1 Levels in Placental Insufficiency Are Associated with Fetal Hypoxia and Angiogenesis. AB - In intrauterine growth restriction (IUGR), a subset of pregnancies undergoes placental vascular dysregulation resulting in restricted blood flow and fetal hypoxemia. Altered transcription of hypoxic regulated plasminogen activator inhibitor 1 (PAI-1) has been associated with pregnancy complications and angiogenic regulation. Here we assessed circulating PAI-1 as an indicator of placental insufficiency. Venous umbilical PAI-1 of hypoxemic (VpO2 20 versus 35 mmHg, p < 0.0001) placental insufficient pregnancies (resistance index 0.9 versus 0.63, p < 0.05) (n = 18) was compared to controls (n = 12). PAI-1 was increased (~10-fold, p < 0.001) and had a positive predictive ratio of 6.7. Further, PAI-1 levels correlated to blood oxygen (r = -0.68, p < 0.0001). The plasma's angiogenic potency measured in vitro was associated with umbilical cord blood PAI 1 levels (r = 0.65, p < 0.01). This association was attenuated by PAI-1 inhibiting antibody (p < 0.001). The results demonstrate PAI-1 as a potential marker of placental insufficiency and identify its close association with pathological hypoxia and angiogenesis in a subset of growth restricted pregnancies. PMID- 26903690 TI - Measurement of the Red Blood Cell Distribution Width Improves the Risk Prediction in Cardiac Resynchronization Therapy. AB - OBJECTIVES: Increases in red blood cell distribution width (RDW) and NT-proBNP (N terminal pro-B-type natriuretic peptide) predict the mortality of chronic heart failure patients undergoing cardiac resynchronization therapy (CRT). It was hypothesized that RDW is independent of and possibly even superior to NT-proBNP from the aspect of long-term mortality prediction. DESIGN: The blood counts and serum NT-proBNP levels of 134 patients undergoing CRT were measured. Multivariable Cox regression models were applied and reclassification analyses were performed. RESULTS: After separate adjustment to the basic model of left bundle branch block, beta blocker therapy, and serum creatinine, both the RDW > 13.35% and NT-proBNP > 1975 pg/mL predicted the 5-year mortality (n = 57). In the final model including all variables, the RDW [HR = 2.49 (1.27-4.86); p = 0.008] remained a significant predictor, whereas the NT-proBNP [HR = 1.18 (0.93-3.51); p = 0.07] lost its predictive value. On addition of the RDW measurement, a 64% net reclassification improvement and a 3% integrated discrimination improvement were achieved over the NT-proBNP-adjusted basic model. CONCLUSIONS: Increased RDW levels accurately predict the long-term mortality of CRT patients independently of NT-proBNP. Reclassification analysis revealed that the RDW improves the risk stratification and could enhance the optimal patient selection for CRT. PMID- 26903692 TI - Doctors as managers of healthcare resources in Nigeria: Evolving roles and current challenges. AB - Over the years, medical practice in Nigeria has evolved in scope and practice, in terms of changing disease patterns, patients' needs, and social expectations. In addition, there is a growing sentiment especially among the general public and some health workers that most doctors are bad managers. Besides drawing examples from some doctors in top management positions that have performed less creditably, critics also harp on the fact that more needs to be done to improve the training of doctors in health management. This article describes the role of doctors in this changing scene of practice and highlights the core areas where doctors' managerial competencies are required to improve the quality of healthcare delivery. Areas such as health care financing, essential drugs and supplies management, and human resource management are emphasized. Resources to be managed and various skills needed to function effectively at the different levels of management are also discussed. To ensure that doctors are well-skilled in managerial competencies, the article concludes by suggesting a curriculum review at undergraduate and postgraduate levels of medical training to include newer but relevant courses on health management in addition to the existing ones, whereas also advocating that doctors be incentivized to go for professional training in health management and not only in the core clinical specialties. PMID- 26903691 TI - Impact of S100A4 Expression on Clinicopathological Characteristics and Prognosis in Pancreatic Cancer: A Meta-Analysis. AB - BACKGROUND: The small Ca(2+)-binding protein S100A4 is identified as a metastasis associated or metastasis-inducing protein in various types of cancer. The goal of this meta-analysis was to evaluate the relationship between S100A4 expression and clinicopathological characteristics and prognosis of patients with pancreatic cancer. METHODS: A comprehensive literature search was carried out in the electronic databases PubMed and Chinese CNKI. Only the studies reporting the correlation between S100A4 expression and clinicopathological characteristics or overall survival (OS) of patients with pancreatic cancer are enrolled. Extracted data was analyzed using the RevMan 5.3 software to calculate the pooled relative risks (95% confidence interval, CI) for statistical analyses. RESULTS: Seven studies including a total of 474 patients were enrolled into this meta-analysis. Negative expression of S100A4 was significantly associated with higher 3-year OS rate (RR = 3.92, 95% CI = 2.24-6.87, P < 0.0001), compared to S100A4-positive cases. Moreover, negative expression of S100A4 was also related to N0 stage for lymph node metastasis (RR = 2.15, 95% CI = 1.60-2.88, P < 0.0001). However, S100A4 expression was not significantly correlated with histological types and distant metastasis status. CONCLUSION: S100A4 expression represents a potential marker for lymph node metastasis of pancreatic cancer and a potential unfavorable factor for prognosis of patients with this disease. PMID- 26903693 TI - Early response to medical treatment of trigeminal neuralgia in a Nigerian population. AB - BACKGROUND: This study evaluates the clinical profile of patients suffering from trigeminal neuralgia (TN) and correlates the findings with early response of the patients to medical treatment. PATIENTS AND METHODS: A 4-year prospective study in which patients diagnosed of TN were treated medically and followed up weekly for 8 weeks to determine early treatment outcome, in the University of Benin Teaching Hospital, Benin City, Nigeria. RESULTS: Of the 287 patients seen during the study period, a total of 14 (4.9%) patients were diagnosed of TN. Thirteen (4.5%) of the cases were selected based on compliance to the 8-week follow-up visits, consisting of 8 (61.5%) males and 5 (38.5%) females, giving a ratio of 1.6:1. The mean age of the patients was 50+/-1.5 years. The mandibular (n = 6, 46.2%) and maxillary (n = 5, 38.5%) divisions of the trigeminal nerve were mostly affected. The lesion was slightly more common on the right side of the face (n = 7, 53.8%) than the left side (n = 6, 46.2%). Talking (n=4, 30.8%) and chewing (n = 3, 23.1%) were the most frequent trigger factors. The patients mostly described the pain as severe, spontaneous, and sharp (n = 5, 38.2%). Most patients became stable on tablets carbamazepine 200 mg 12 hourly, folic acid 5 mg daily, and phenytoin 100 mg daily. Good response was observed in most patients within 2 weeks (n = 6, 46.2%) of medical treatment, especially in patients at the seventh decade of age (n = 3, 23.1%) and those with lesions involving the mandibular division of the trigeminal nerve (n = 3, 23.1%). CONCLUSION: This study shows early response of TN to medical treatment. We recommend combination therapy of carbamazepine and folic acid in the treatment of patients, especially elderly patients with lesions involving the mandibular division of the trigeminal nerve. PMID- 26903694 TI - A 20-year retrospective study of histopathologic patterns of gonadal germ cell tumors in males in the University of Benin Teaching Hospital. AB - BACKGROUND: Localization of germ cells tumors to the gonads is not uncommon and has been shown to possess good prognosis with appropriate treatment. Studies on the prevalence and histopathologic features of these tumors in Nigerians are, however, rare. This study was, therefore, aimed at determining the pattern of gonadal germ cell tumors (GGCTs) in Benin and environs. MATERIALS AND METHODS: This was a 20-year retrospective study conducted at the University of Benin Teaching Hospital 9-(UBTH), a tertiary health facility in Benin City. Data were obtained from the histopathology day book of the Department of Morbid Anatomy of the UBTH, and permission was obtained from the UBTH Ethics Committee protocol number ADM/E 22/A/VOL.VH/928 with results displayed in tables and figures. RESULTS: Intratubular germ cell neoplasms (ITGN) was the most common GGCT with about 33.3% of the total and was distributed within the fourth to fifth decades of life; benign cystic teratoma and choriocarcinoma were observed to have a low occurrence with 8.3% each found in age groups 11-20 and 21-30 years, respectively. The studied gonadal lesions were most frequent at the left testis and were predominantly premalignant forms. CONCLUSION: This was an index study on patterns of GGCTs in males in UBTH, and it showed that GGCTs in males were predominantly premalignant with ITGN as the most common type of testicular germ cell tumors. PMID- 26903695 TI - Cerumen impaction: Challenges and management profile in a rural health facility. AB - BACKGROUND: Cerumen impaction is a worldwide problem. It constitutes a significant proportion of health problems in many settings and its prevalence varies. Very few studies were done in this region with none from our center. The aim of this study is to review the challenges and management profile of cerumen impaction in a rural health facility in Nigeria. MATERIALS AND METHODS: This was a 3-year retrospective study of all patients that were managed for cerumen impaction from June 2008 to May 2011, in the Department of Otorhinolaryngology, Federal Medical Centre, Ido-Ekiti, Nigeria. RESULTS: A total of 239 patients, aged 3-98 years were managed for cerumen impaction. The male: female ratio was 1.6:1. The age group 1-20 years was mostly affected in 29.3%. Major complaints were hearing impairment in 120 cases. Both ears were mostly affected in 48.5% of the patients. Olive oil was a major ceruminolytic agent used in 95.4%. Ear syringing was carried out in 91.2% of cases. Major complications were bruises of external auditory canal and otalgia in 7.3% of cases each. Forty-two (17.8%) of our patients were asymptomatic, and they did not complained of ear problem. Out of those patients that were symptomatic, 44.3% had visited general medical practitioners and non-otolaryngologist, while 27.6% had self-medication or visited chemist for their ear complaints. Only 3.7% of them had been seen by ear, nose, and throat (ENT) specialist in the past. CONCLUSION: Cerumen impaction is a common otolaryngological problem that presents to ENT surgeon, children, and elderly are more affected. Hearing impairment is the major complaint which may increase the burden of disability on society. Syringing is the most common mode of treatment of our patients. Continuing medical education, proper otological examination by the non-otolaryngologist and public health education to improve the low level of awareness on danger of self-medication is essential. PMID- 26903696 TI - Assessment of some cardiovascular risk factors in predialysis chronic kidney disease patients in Southern Nigeria. AB - BACKGROUND: Cardiovascular risk factors are responsible for cardiovascular disease and rapid progression of chronic kidney disease (CKD) to end-stage renal disease. Prompt evaluation, modification, and treatment of these factors in predialysis patients will reduce morbidity and mortality. This study assessed some cardiovascular risk factors in predialysis CKD patients in a tertiary hospital in Southern Nigeria. PATIENTS AND METHODS: This was a case-control study that involved 76 consecutive predialysis CKD patients and 38 age-and sex-matched controls without CKD over 1 year period. Both groups were assessed for cardiovascular risk factors, and comparisons were made. A P value of <0.05 was taken as significant. RESULTS: The mean ages of the CKD versus control group were 48.00 +/- 15.28 versus 45.34 +/- 15.35 years. The male:female ratio was 1.7:1 for both groups. The common etiologies of CKD in this study were hypertension 30 (39.5%), diabetes mellitus 23 (30.3%), and chronic glomerulonephritis 19 (25%). There were 38 (50%) in CKD stage 3, 31 (40.8%) in CKD stage 4, and 7 (9.2%) in CKD stage 5. The common cardiovascular risk factors found in the CKD versus control were hypertension (96.1% vs. 42.1%), anemia (96.1% vs. 23.7%), left ventricular hypertrophy (77.6% vs. 23.7%), dyslipidemia (67.1% vs. 39.5%), hypocalcemia (60.1% vs. 18.5%), hyperphosphatemia (63.2% vs. 0%), and hyperuricemia (57.9% vs. 15.8%). These risk factors were significantly higher in CKD group. Hyperphosphatemia and hypoalbuminemia significantly increased across CKD stages 3-5. Anemia was significantly more common in males whereas dyslipidemia was more common in female CKD patients. CONCLUSION: Cardiovascular risk factors were highly prevalent in predialysis CKD subjects even in early stages. Hypoalbuminemia and hyperphosphatemia significantly increased across the CKD stages 3-5 whereas anemia and dyslipidemia showed significant gender differences. Cardiovascular risk factors should be treated early in predialysis CKD patients. PMID- 26903697 TI - Bacteriological evaluation for one-and two-piece implant design supporting mandibular overdenture. AB - BACKGROUND: This study evaluated and compared the bacteriological effect of two piece implants and one-piece implants in complete overdenture cases on supporting structures. MATERIALS AND METHODS: Ten male completely edentulous patients were selected and randomly divided into two equal groups according to the implant design and surgical technique for this study; Group 1: Patients were rehabilitated with complete mandibular overdenture supported by two-piece implants one on each side of the lower arch following two-stage surgical technique and Group 2: Patients were rehabilitated with complete mandibular overdenture supported by one-piece implants one on each side. Evaluation was made at the time of insertion, 6, 12, and 18 months after overdenture insertion, by measuring bacteriological changes around implants abutments. RESULTS: Complete overdenture supported by one-piece implants showed better effect on the bacteriological changes as compared to that supported by two-piece implants. CONCLUSION: Complete overdenture supported by one-piece implants one on each side of the lower arch showed better effect on the bacteriological changes than using the same prosthesis supported by two-piece implants. PMID- 26903698 TI - Self-reported sulphonamide hypersensitivity reactions in adults living in Ibadan, Nigeria: A cross-sectional, community-based study. AB - BACKGROUND: Documentation of adverse drug reactions (ADRs) is critical to a safe health delivery system. The aim of our study was to explore the prevalence of self-reported sulphonamide hypersensitivity reactions in a community-based sample of the general population in Ibadan, Nigeria. We also examined sociodemographic factors associated with ADRs in the sample. PATIENTS AND METHODS: The study was cross-sectional in design with study sites in urban, semiurban, and rural settlement areas. Pretested questionnaires were administered on a one-on-one basis by trained interviewers. Frequency tables and percentages were computed for various levels of the variables. Chi-square test was used to assess the relationship between sulphonamide hypersensitivity and variables such as sociodemographic characteristics of respondents, respondents' knowledge of drugs, as well as drug sources. Variables found to be significantly associated with sulphonamide hypersensitivity were further investigated using multiple logistic regressions analysis. RESULTS: Out of the 1062 respondents, 15.5% reported hypersensitivity to sulphonamides with skin reactions being the most prevalent. The proportion reporting ADRs was significantly higher among respondents with tertiary education (23.1%) than any other level of education (P = 0.008). In addition, individuals who were very knowledgeable about drug use (odds ratio[OR]: 2.07; 95% confidence interval [CI]: 1.15-3.73) and persons who got drugs from hospitals (OR: 2.00; 95% CI: 1.10-3.65) were more likely to report ADRs than those who were ignorant about drugs and those who purchased drugs from open markets, respectively. CONCLUSION: Prevalence of sulphonamide hypersensitivity is high among respondents, and ADRs is likely to be reported by people who are knowledgeable about drug use. PMID- 26903699 TI - Determinants and outcome of fetal macrosomia in a Nigerian tertiary hospital. AB - BACKGROUND: To determine the incidence and risk factors of fetal macrosomia and maternal and perinatal outcome. PATIENTS AND METHODS: This was a 1-year prospective case-control study of singleton pregnancies in a Nigerian tertiary hospital. Only women who gave consent were recruited for the study. The maternal and perinatal outcomes in women who delivered macrosomic infants (birth weight >= 4000 g) were compared with the next consecutive delivery of normal birth weight (2500-3999 g) infants. RESULTS: The total deliveries for the study period were 2437, of which 135 were macrosomic babies. The incidence of fetal macrosomia was 5.5%. The mean birth weights of macrosomic and nonmacrosomic babies were 4.26 +/- 0.29 kg and 3.20 +/- 0.38 kg, respectively, P = 0.000. Mothers with macrosomic babies were more likely to be older (P = 0.047), of higher parity (0.001), taller (P = 0.007), and weighed more at delivery (P = 0.000). Previous history of fetal macrosomia (P = 0.000) and maternal diabetes (P = 0.007) were factors strongly associated with the delivery of macrosomic infants. Pregnancies associated with fetal macrosomia had increased duration of labor (P = 0.007), interventional deliveries (P = 0.000), shoulder dystocia, and genital laceration (P = 0.000). There was no significant difference in the incidence of primary postpartum hemorrhage (P = 0.790), birth asphyxia, and perinatal mortality (P = 0.197). CONCLUSION: Fetal macrosomia is associated with maternal and fetal morbidities. The presence of the observed risk factors should elicit the suspicion of a macrosomic fetus and the need for appropriate management to reduce maternal and fetal morbidities. PMID- 26903700 TI - Independent and joint effects of serum 25-hydroxivitamin D and calcium on breast cancer ratio in an Iran population: A cross-sectional study. AB - BACKGROUND: It has been suggested that Vitamin D and calcium have protective effects against breast cancer. The results about breast cancer and serum Vitamin D and calcium levels are still controversial, indefinite, and insufficient to determine the amount of nutritional needs. Thus, we investigated the association between serum 25-hydroxyvitamin D(25-OH-D) and calcium on the ratio of breast cancer at diagnosis time. MATERIALS AND METHODS: We carried out a hospital-based cross-sectional study in a population of Iran. It comprised 57 breast cancer cases, who were newly diagnosed, and 85 controls in 2013. The serum 25-OH-D and calcium levels were measured. RESULTS: There was not any significant association between 25-OH-D and breast cancer ratio. Odds ratio (OR) comparing the highest quartile to the lowest quartile was 1.03(95% confidence interval[CI] 0.33-3.22, P trend 0.95). Having sufficient (>75 nmol/L) serum 25-OH-D levels compared to insufficient serum 25-OH-D levels was not associated with a significantly decreased ratio of breast cancer (OR 0.55, 95% CI 0.23-1.29, P = 0.17). Furthermore, an association between calcium and breast cancer did not get statistical significance (OR 0.51, 95% CI 0.17-1.49, P-trend 0.31). The joint effect was negative interaction. CONCLUSION: Vitamin D and calcium do not act on decreasing ratio of breast cancer. Decreasing ratio of breast cancer in relation to serum calcium and Vitamin D level at diagnosis time needs more assessments. PMID- 26903701 TI - Pitfalls of antiretroviral drug resistance genotyping of HIV-1 Group M and Group N from Cameroon by sequenced-based assays. AB - BACKGROUND: HIV-1 genotyping for antiretroviral drug resistance mutations (DRMs) were developed based basically on subtype B HIV-1 Group M, which represents only 10% of HIV strains worldwide. In sub-Saharan Africa, non-B subtypes HIV-1 largely predominate and HIV-1 genetic diversity could affect the performance of drug resistance genotyping assays. We compared prospectively the performance of the ViroSeq((r)) and Trugene((r)) genotyping assays to detect DRM in HIV-1-infected adult patients living in Douala, Cameroun. MATERIALS AND METHODS: DRM in protease (P) and reverse transcriptase (RT) genes were assessed in parallel using both ViroSeq((r)) and Trugene((r)) assays in plasma samples from 45 first-line antiretroviral treatment-experienced patients in Douala, Cameroon. RESULTS: Trugene HIV-1 Genotyping Assay((r)) (Siemens Health Care Diagnostics, NY, USA) and ViroSeq HIV-1 Genotyping System((r))(Celera Diagnostics, CA, USA) assessed equivalently antiretroviral DRMs in P and RT genes from non-B HIV-1 Group M in 44 Cameroonian adults in virological failure; Trugene((r)) was slightly more sensitive than ViroSeq((r)) (100% vs. 91%). One patient infected by HIV-1 Group N was successfully amplified only by the Trugene HIV-1 Genotyping assay((r)), while ViroSeq HIV-1 Genotyping System v2.0((r)) assay could not. CONCLUSION: Results showed the higher performance of the Trugene((r)) system to detected and amplify P and RT genes targeting DRM to the principal antiretroviral drugs used in sub Saharan Africa. Discrepancies between the results of HIV viral load assays and molecular tests should alert clinicians and virologists to the possibility of infection by an atypical variant virus, especially in Central Africa where very broad HIV-1 genetic diversity exists. PMID- 26903702 TI - A cross-sectional study of the knowledge and attitude of medical laboratory personnel regarding continuing professional development. AB - BACKGROUND: Continuing professional development (CPD) in Medical Laboratory Scientists (MLS) is aimed at equipping laboratory professionals with the necessary skills to enhance practice. The laboratory scientists are usually the first contact between the patient and health care system in aspects of diagnosis and monitory of diseases. As such, it becomes imperative to assess the knowledge of laboratory personnel regarding CPD. MATERIALS AND METHODS: Self-administered questionnaires were distributed to 200 laboratory personnel's attending the maiden CPD workshop organized by the Association of MLS in Jos the Plateau state capital. RESULTS: One hundred and thirty-five (82 males and 53 females) of the 200 administered questionnaires were returned. Only 32 of them (23.7%) attended CPD program in the last 1 year with 10 (7.5%) engaging in online CPD. Five (3.7%) of the respondents had the privilege to attend an international CPD. Majority (95.2%) of the respondents identified CPD as an essential component of professional career development. Lack of sponsorship was identified as a major setback in CPD efficiency by 93.8% of respondents. About 58 (46.4%) noted that poor attendance in CPD workshops was due to unavailability of policy guideline for CPD. One hundred and twenty (95.2%) of respondents had an aim of improving their skills after attending CPD workshops. CONCLUSION: The overall attitude of Nigerian MLS toward attending CPD workshop is poor; however, the knowledge regarding the importance of CPD is adequate. There exists a gap between sponsorship for CPD by various institutions and MLS. PMID- 26903703 TI - Cardiac dysrhythmia resulting from antibiotic abuse. AB - Antibiotics are commonly used to combat infections and could be used in treating some connective diseases. They are not without side effects especially when used without regard to age, gender, diseases and their severity, comorbidity, and idiosyncrasies. This is more likely to occur when dispensed by unqualified persons to selves or others. Consequences of inappropriate use include various morbidities and in some instances death. This is a report of a middle-aged man with several risk factors for cardiovascular disease, who on the side had chronic osteomyelitis. Wound swab grew organisms sensitive to levofloxacin, and he had the drug prescribed to him by the attending orthopedic surgeon. With reduction in discharge to the point that he no longer bound his foot in bandage, he went on using the drug beyond the duration of prescription without reverting to his orthopedic surgeon until he developed sudden onset palpitation and shortness of breath. With this was an unusual tachyarrhythmia which defied initial measures. This prompted further review of his drug history when he admitted to taking levofloxacin for up to 3 months. Suspecting it to be the culprit, he was advised to discontinue it. With this, his symptoms started to abate, alongside gradual improvement in electrocardiograms till eventual normalization. This report is made to highlight the possibility that some antibiotics have the propensity to induce arrhythmias that can be very serious especially in cardiovascular disease burdened patients. Such patients then go into heart failure and it becomes difficult to tell which came first, the arrhythmia or the heart failure. Resolving the order of onset assists in proper management. As a result, it is being recommended that patients with unexplained arrhythmias with or without heart failure should have their drug histories evaluated. Uncontrolled prescription and use of antibiotics should also be discouraged. PMID- 26903704 TI - Report of a case of papillary thyroid carcinoma in association with Hashimoto's thyroiditis. AB - Hashimoto thyroiditis (HT) is an autoimmune disease, known to be the most common cause of hypothyroidism in nonendemic goitrous areas. It is usually characterized by symmetric, painless, and diffused but sometimes localized swelling of the thyroid gland with features of hypothyroidism. Papillary thyroid carcinoma (PTC), on the other hand, is the most common yet less aggressive form of thyroid cancer, especially in iodine-deficient areas. The coexistence of the two diseases is possible but not common. This case study reports a 50-year-old female with a 10 year history of a huge goiter, which was essentially symptom-free until about 3 months prior to presentation when the patient started complaining of neck pain, dysphagia, productive cough, and cold intolerance. Physical examination revealed focal cystic and tender area in the multinodular swelling and associated cervical lymphadenopathy on the left side of the neck. The serum thyroid stimulating hormone was high, sub-normal T3, and the T4 was low. The fine needle aspiration cytology yielded 10 ml of aspirate of pus admixed with altered blood which on microscopy showed a few suspicious follicular epithelial cells with open nuclei admixed with mainly neutrophil polymorphs, siderophages, and foam cells in a hemorrhagic background. The patient had an incision biopsy that showed areas displaying PTC and HT. PMID- 26903705 TI - Fast Covariance Estimation for High-dimensional Functional Data. AB - We propose two fast covariance smoothing methods and associated software that scale up linearly with the number of observations per function. Most available methods and software cannot smooth covariance matrices of dimension J > 500; a recently introduced sandwich smoother is an exception but is not adapted to smooth covariance matrices of large dimensions, such as J = 10, 000. We introduce two new methods that circumvent those problems: 1) a fast implementation of the sandwich smoother for covariance smoothing; and 2) a two-step procedure that first obtains the singular value decomposition of the data matrix and then smoothes the eigenvectors. These new approaches are at least an order of magnitude faster in high dimensions and drastically reduce computer memory requirements. The new approaches provide instantaneous (a few seconds) smoothing for matrices of dimension J = 10,000 and very fast (< 10 minutes) smoothing for J = 100, 000. R functions, simulations, and data analysis provide ready to use, reproducible, and scalable tools for practical data analysis of noisy high dimensional functional data. PMID- 26903706 TI - Andrographolide Sodium Bisulfate Prevents UV-Induced Skin Photoaging through Inhibiting Oxidative Stress and Inflammation. AB - Andrographolide sodium bisulfate (ASB), a water-soluble form made from andrographolide through sulfonating reaction, is an antioxidant and anti inflammatory drug; however, the antiphotoaging effect of ASB has still not been revealed. Oxidative stress and inflammation are known to be responsible for ultraviolet (UV) irradiation induced skin damage and consequently premature aging. In this study, we aimed at examining the effect of ASB on UV-induced skin photoaging of mice by physiological and histological analysis of skin and examination of skin antioxidant enzymes and immunity analyses. Results showed that topical administration of ASB suppressed the UV-induced skin thickness, elasticity, wrinkles, and water content, while ASB, especially at dose of 3.6 mg/mouse, increased the skin collagen content by about 53.17%, decreased the epidermal thickness by about 41.38%, and prevented the UV-induced disruption of collagen fibers and elastic fibers. Furthermore, ASB decreased MDA level by about 40.21% and upregulated the activities of SOD and CAT and downregulated the production of IL-1beta, IL-6, IL-10, and TNF-alpha in UV-irradiated mice. Our study confirmed the protective effect of ASB against UV-induced photoaging and initially indicated that this effect can be attributed to its antioxidant and anti-inflammatory activities in vivo, suggesting that ASB may be a potential antiphotoaging agent. PMID- 26903707 TI - Decreased Interleukin-4 Release from the Neurons of the Locus Coeruleus in Response to Immobilization Stress. AB - It has been demonstrated that immobilization (IMO) stress affects neuroimmune systems followed by alterations of physiology and behavior. Interleukin-4 (IL-4), an anti-inflammatory cytokine, is known to regulate inflammation caused by immune challenge but the effect of IMO on modulation of IL-4 expression in the brain has not been assessed yet. Here, it was demonstrated that IL-4 was produced by noradrenergic neurons in the locus coeruleus (LC) of the brain and release of IL 4 was reduced in response to IMO. It was observed that IMO groups were more anxious than nontreated groups. Acute IMO (2 h/day, once) stimulated secretion of plasma corticosterone and tyrosine hydroxylase (TH) in the LC whereas these increments were diminished in exposure to chronic stress (2 h/day, 21 consecutive days). Glucocorticoid receptor (GR), TH, and IL-4-expressing cells were localized in identical neurons of the LC, indicating that hypothalamic-pituitary-adrenal- (HPA-) axis and sympathetic-adrenal-medullary- (SAM-) axis might be involved in IL-4 secretion in the stress response. Accordingly, it was concluded that stress induced decline of IL-4 concentration from LC neurons may be related to anxiety like behavior and an inverse relationship exists between IL-4 secretion and HPA/SAM-axes activation. PMID- 26903708 TI - Osteoclasts Are Required for Hematopoietic Stem and Progenitor Cell Mobilization but Not for Stress Erythropoiesis in Plasmodium chabaudi adami Murine Malaria. AB - The anemia and inflammation concurrent with blood stage malaria trigger stress haematopoiesis and erythropoiesis. The activity of osteoclasts seems required for the mobilization of hematopoietic stem and progenitor cells (HSPC) from the bone marrow to the periphery. Knowing that BALB/c mice with acute Plasmodium chabaudi adami malaria have profound alterations in bone remodelling cells, we evaluated the extent to which osteoclasts influence their hematopoietic response to infection. For this, mice were treated with osteoclast inhibiting hormone calcitonin prior to parasite inoculation, and infection as well as hematological parameters was studied. In agreement with osteoclast-dependent HSPC mobilization, administration of calcitonin led to milder splenomegaly, reduced numbers of HSPC in the spleen, and their retention in the bone marrow. Although C-terminal telopeptide (CTX) levels, indicative of bone resorption, were lower in calcitonin treated infected mice, they remained comparable in naive and control infected mice. Calcitonin-treated infected mice conveniently responded to anemia but generated less numbers of splenic macrophages and suffered from exacerbated infection; interestingly, calcitonin also decreased the number of macrophages generated in vitro. Globally, our results indicate that although osteoclast dependent HSC mobilization from bone marrow to spleen is triggered in murine blood stage malaria, this activity is not essential for stress erythropoiesis. PMID- 26903709 TI - The Role of the IL-20 Subfamily in Glaucoma. AB - Glaucoma is a common disease that leads to loss of peripheral vision and, if left untreated, ultimately to blindness. While the exact cause(s) of glaucoma is still unknown, two leading risk factors are age and elevated intraocular pressure. Several studies suggest a possible link between glaucoma and inflammation in humans and animal models. In particular, our lab recently identified a T104M mutation in IL-20 receptor-B (IL-20RB) in primary open angle glaucoma patients from a large pedigree. Several of the interleukin- (IL-) 20 family of cytokines and receptors are expressed in ocular tissues including the trabecular meshwork, optic nerve head, and retinal ganglion cells. The DBA/2J mouse develops high intraocular pressures with age and has characteristic optic nerve defects that make it a useful glaucoma model. IL-24 expression is significantly upregulated in the retina of these mice, while IL-20RA expression in the optic nerve is downregulated following pressure-induced damage. The identification of a mutation in the IL-20RB gene in a glaucoma pedigree and changes in expression levels of IL 20 family members in the DBA/2J mouse suggest that disruption of normal IL-20 signaling in the eye may contribute to degenerative processes associated with glaucoma. PMID- 26903710 TI - Relationship between Sustained Reductions in Plasma Lipid and Lipoprotein Concentrations with Apheresis and Plasma Levels and mRNA Expression of PTX3 and Plasma Levels of hsCRP in Patients with HyperLp(a)lipoproteinemia. AB - The effect of lipoprotein apheresis (Direct Adsorption of Lipids, DALI) (LA) on plasma levels of pentraxin 3 (PTX3), an inflammatory marker that reflects coronary plaque vulnerability, and expression of PTX3 mRNA was evaluated in patients with hyperLp(a)lipoproteinemia and angiographically defined atherosclerosis/coronary artery disease. Eleven patients, aged 55 +/- 9.3 years (mean +/- SD), were enrolled in the study. PTX3 soluble protein levels in plasma were unchanged by 2 sessions of LA; however, a downregulation of mRNA expression for PTX3 was observed, starting with the first session of LA (p < 0.001). The observed reduction was progressively increased in the interval between the first and second LA sessions to achieve a maximum decrease by the end of the second session. A statistically significantly greater treatment-effect correlation was observed in patients undergoing weekly treatments, compared with those undergoing treatment every 15 days. A progressive reduction in plasma levels of C-reactive protein was also seen from the first session of LA, with a statistically significant linear correlation for treatment-effect in the change in plasma levels of this established inflammatory marker (R(2) = 0.99; p < 0.001). Our findings suggest that LA has anti-inflammatory and endothelium protective effects beyond its well-established efficacy in lowering apoB100-containing lipoproteins. PMID- 26903711 TI - Enigma of IL-17 and Th17 Cells in Rheumatoid Arthritis and in Autoimmune Animal Models of Arthritis. AB - Rheumatoid arthritis (RA) is one of the most common autoimmune disorders characterized by the chronic and progressive inflammation of various organs, most notably the synovia of joints leading to joint destruction, a shorter life expectancy, and reduced quality of life. Although we have substantial information about the pathophysiology of the disease with various groups of immune cells and soluble mediators identified to participate in the pathogenesis, several aspects of the altered immune functions and regulation in RA remain controversial. Animal models are especially useful in such scenarios. Recently research focused on IL 17 and IL-17 producing cells in various inflammatory diseases such as in RA and in different rodent models of RA. These studies provided occasionally contradictory results with IL-17 being more prominent in some of the models than in others; the findings of such experimental setups were sometimes inconclusive compared to the human data. The aim of this review is to summarize briefly the recent advancements on the role of IL-17, particularly in the different rodent models of RA. PMID- 26903712 TI - 12 Weeks of Combined Endurance and Resistance Training Reduces Innate Markers of Inflammation in a Randomized Controlled Clinical Trial in Patients with Multiple Sclerosis. AB - Previously, we reported that patients with multiple sclerosis (MS) demonstrate improved muscle strength, exercise tolerance, and lean tissue mass following a combined endurance and resistance exercise program. However, the effect of exercise on the underlying disease pathogenesis remains elusive. Since recent evidence supports a crucial role of dendritic cells (DC) in the pathogenesis of MS, we investigated the effect of a 12-week combined exercise program in MS patients on the number and function of DC. We demonstrate an increased number of plasmacytoid DC (pDC) following the exercise program. These pDC display an activated phenotype, as evidenced by increased numbers of circulating CD62L(+) and CD80(+) pDC. Interestingly, the number of CD80(+) pDC positively correlates with the presence of IL-10-producing regulatory type 1 cells (Tr1), an important cell type for maintaining peripheral tolerance to self-antigens. In addition, decreased production of the inflammatory mediators, TNF-alpha and MMP-9, upon Toll-like receptor (TLR) stimulation was found at the end of the exercise program. Overall, our findings suggest that the 12-week exercise program reduces the secretion of inflammatory mediators upon TLR stimulation and promotes the immunoregulatory function of circulating pDC, suggestive for a favorable impact of exercise on the underlying immunopathogenesis of MS. PMID- 26903713 TI - Hypovitaminosis D3, Leukopenia, and Human Serotonin Transporter Polymorphism in Anorexia Nervosa and Bulimia Nervosa. AB - Vitamin D3 has been described to have different extraskeletal roles by acting as parahormone in obesity, diabetes, cancer, cognitive impairment, and dementia and to have important regulatory functions in innate immunity. There are no studies showing extraskeletal changes associated with hypovitaminosis D3 in eating disorders. Methods. We have analyzed the blood of 18 patients affected by anorexia nervosa and bulimia nervosa collected over a 15-month period. We performed a panel of chemical and clinical analyses: the assay of vitamin D3, the immunoblotting of vitamin D receptor and peroxisome proliferator-activated receptor gamma, and the genotyping of 5-hydroxytryptamine transporter linked polymorphic region. Results. We choose 18 patients with a normal blood test profile such as thyroid hormones, hepatic and renal parameters, triglycerides, proteins, vitamin B12, and folic acid. Among these emerged the case of a woman with long-term anorexia nervosa and the case of a woman with long-term bulimia nervosa both complicated by anxiety and depression, severe hypovitaminosis D3, decrease of vitamin D receptor, leukopenia, and 5-hydroxytryptamine transporter linked polymorphic region short allele. Conclusion. The results induce hypothesising that the severe hypovitaminosis D3 might be responsible for the lack of the inflammatory response and the depressive symptoms in patients with long-term eating disorders. PMID- 26903714 TI - The Impact of Obstructive Sleep Apnoea and Nasal Continuous Positive Airway Pressure on Circulating Ischaemia-Modified Albumin Concentrations. AB - The aim of the present study was to evaluate the impact of obstructive sleep apnoea syndrome (OSAS) and the effects of nasal continuous positive airway pressure (CPAP) on circulating ischaemia-modified albumin (IMA) concentrations. The study included 97 newly diagnosed OSAS patients and 30 nonapnoeic controls. Blood samples were obtained in the morning after polysomnography. After 3 months of CPAP treatment, 31 patients with moderate-severe OSAS were reassessed for serum IMA concentrations. Significantly higher serum IMA concentrations were measured in the OSAS group than in the control group [0.518 +/- 0.091 absorbance units (ABSU), 0.415 +/- 0.068 ABSU, P < 0.001]. Serum IMA concentrations correlated significantly with the apnoea-hypopnoea index, mean SaO2, desaturation index, and C-reactive protein concentrations. Multiple logistic regression analyses showed that OSAS increased the serum IMA concentration independent of age, sex, body mass index, smoking habit, and cardiovascular disease. After 3 months of treatment with CPAP, OSAS patients had significantly lower serum IMA concentrations (0.555 +/- 0.062 ABSU to 0.431 +/- 0.063 ABSU, P < 0.001). The results showed that OSAS is associated with elevated concentrations of IMA, which can be reversed by effective CPAP treatment. PMID- 26903715 TI - Th17 Cytokines Disrupt the Airway Mucosal Barrier in Chronic Rhinosinusitis. AB - Cytokine mediated changes in paracellular permeability contribute to a multitude of pathological conditions including chronic rhinosinusitis (CRS). The purpose of this study was to investigate the effect of interferons and of Th1, Th2, and Th17 cytokines on respiratory epithelium barrier function. Cytokines and interferons were applied to the basolateral side of air-liquid interface (ALI) cultures of primary human nasal epithelial cells (HNECs) from CRS with nasal polyp patients. Transepithelial electrical resistance (TEER) and permeability of FITC-conjugated dextrans were measured over time. Additionally, the expression of the tight junction protein Zona Occludens-1 (ZO-1) was examined via immunofluorescence. Data was analysed using ANOVA, followed by Tukey HSD post hoc test. Our results showed that application of interferons and of Th1 or Th2 cytokines did not affect the mucosal barrier function. In contrast, the Th17 cytokines IL-17, IL-22, and IL-26 showed a significant disruption of the epithelial barrier, evidenced by a loss of TEER, increased paracellular permeability of FITC-dextrans, and discontinuous ZO-1 immunolocalisation. These results indicate that Th17 cytokines may contribute to the development of CRSwNP by promoting a leaky mucosal barrier. PMID- 26903716 TI - Choroidal imaging: Looking ahead. PMID- 26903717 TI - Femtosecond laser assisted cataract surgery, beginning of a new era in cataract surgery. AB - The purpose of this article is to analyze and understand the mechanism of action, effectiveness, cost and time benefits, advantages and disadvantages of the femtosecond laser (FSL) assisted cataract surgery. A PubMed search was done using the topic and the keywords. Research shows considerable improvements in corneal incisions, anterior capsulotomy, and phacofragmentation using FSL. We will also discuss and compare FSL with conventional cataract extraction techniques in terms of both short-term and long-term advantages and disadvantages. Limitations of the studies reviewed include small sample size and short-term follow-up. The major dilemma is still considered to be its heavy financial feasibility to date. PMID- 26903718 TI - Phlyctenular keratoconjunctivitis among children in the tertiary eye hospital of Kathmandu, Nepal. AB - BACKGROUND: This study was conducted to determine clinical profile and etiological factors for phlyctenular keratoconjunctivitis (PKC) in our patients. MATERIALS AND METHODS: In the descriptive study, 50 pediatric cases of PKC were enrolled into the study from outpatient department of BP Koirala Lions Center for Ophthalmic Studies between August 2011 and August 2012. The age, sex, exposure to tuberculosis, ocular symptoms, and systemic complaints were recorded. Morphological description of PKC such as number, type, location and scars HISTORY and number of recurrence was also noted. The conjunctival swab was taken from all patients and sent for microbiological examination. Report of systemic involvement, worm infestation was also noted. Mantoux testing for possibility of tuberculosis was also performed. RESULTS: PKC was detected in 59 eyes of 50 children having mean age of 8.0 +/- 6.2 years including 54% males, unilateral involvement in 82%, the limbal involvement in 52% and multiple PKC in 34% children. Associated ocular disorder was blepharitis in 12 (24%) children. Conjunctival swab and culture revealed Staphylococcus infection in 10 (20%) children. Of eight recurrent cases, two had urinary tract infection managed with systemic antibiotics, three had parasitic infestation treated with antihelmentics, one had mantoux positive without having evidence of tuberculosis and two cases had blepharitis as a local factor. CONCLUSIONS: PKC is mostly presented as unilateral disorder of conjunctiva. PKC is associated with blepharitis, Staphylococcus infection, worm infestation and systemic infection. PMID- 26903719 TI - Prevalence and associated factors of dry eye: Our experience in patients above 40 years of age at a Tertiary Care Center. AB - CONTEXT: Dry eye is a very common as well as under-diagnosed ocular disorder. It is not only troublesome in terms of its symptoms but also imposes a great financial burden. AIMS: To determine the prevalence of dry eye in ophthalmology out-patients at a Tertiary Care Hospital and its association with various clinico epidemiological factors. SETTINGS AND DESIGN: A hospital-based study at a Tertiary Care Center was conducted including 400 out-patients of age 40 years and above. MATERIALS AND METHODS: Patients were consecutively selected and underwent a routine ophthalmological examination along with tear film break-up time (TBUT) as a screening tool for detecting the presence of dry eye. STATISTICAL ANALYSIS: We performed a descriptive, univariate and multivariable logistic regression analysis to calculate odds ratios and 95% confidence interval. RESULTS: The mean age of the study population was 58.6 years. The overall prevalence of dry eye was found to be 54.3%. An association was found between dry eye prevalence and outdoor workers, participants working indoor using air conditioners, housewives, diabetics, patients who have undergone previous ocular surgery and those with meibomian gland dysfunction. CONCLUSIONS: Dry eye is a very common condition with a high prevalence among the elderly. We recommend the screening of all out patients by TBUT, which is a simple test to perform and examination of lids for meibomian gland disease, which if present can be treated. Further studies are needed to establish uniform diagnostic criteria for dry eye, which will help to get more concrete prevalence data, as well as its etiological factors. PMID- 26903721 TI - Magnitude and determinants of diabetic retinopathy among persons with diabetes registered at employee health department of a tertiary Eye Hospital of central Saudi Arabia. AB - BACKGROUND: To estimate the magnitude and determinants of diabetic retinopathy (DR) among persons with diabetes registered at the employee health department of King Khaled Eye Specialist Hospital (KKESH). METHODS: A retrospective review of medical records was conducted in 2013-14 at KKESH. The case record review extracted demographic, profile of diabetes, diabetic complications, and different blood indices to determine the status of potential risk factors. Ocular profile, especially DR was also noted. RESULTS: Our cohort had 94 staff with diabetes. Eye examination was carried out in 51 (54.8%) of them. The rate of DR was 52% (95% confidence interval (CI) 28-66). Sight-threatening diabetic retinopathy (STDR) (proliferative DR and/or diabetic macular edema) was present in 40% of those examined. Good glycemic control was noted in 42% of participants. Duration of diabetes was associated with DR (P = 0.04). Good glycemic control was negatively associated to DR (odds ratio = 0.2 [95% CI 0.04-0.6]). The coverage of eye screening was 55% only. Laser treatment was given to 80% of STDR cases. The lens opacity and glaucoma rate was 15% and 8.3%, respectively. CONCLUSIONS: Low coverage for eye screening and laser treatment to diabetics among the staff of an eye hospital is a matter of concern. The underlying causes of low coverage of screening, digital fundus photography as a screening tool and management should be addressed. PMID- 26903720 TI - Optic nerve head granuloma as a primary manifestation of ocular sarcoidosis - A tertiary uveitis clinic experience. AB - PURPOSE: To report a case series of ocular sarcoidosis manifesting as optic nerve head granuloma. DESIGN: Observational case series. RESULTS: Unilateral presentation in three females and a male. None of them had symptoms suggestive of systemic involvement. Fundus examination in all the patients showed hyperemic optic discs with peripapillary subretinal granuloma. Serum angiotensin converting enzyme was elevated in all patients. Chest radiograph was within normal limits in all patients. High resolution computed tomography of the chest showed features of sarcoidosis in two patients. All patients were treated with oral steroids. Immunosupressants were given in three patients, intravenous steroid, followed by oral steroids given in three patients. Improvement in visual acuity was noted in all four patients. CONCLUSION: Primary optic nerve involvement in sarcoidosis is rare. Isolated optic nerve sarcoidosis may exist without any systemic manifestations. Corticosteroids with immunosuppressants form the mainstay of therapy. PMID- 26903722 TI - Experience of intravitreal injections in a tertiary Hospital in Oman. AB - AIM: To find out statistical data regarding intravitreal injections in an outpatient department setup at a tertiary center in Oman. DESIGN: Retrospective chart review. METHODS: Data collection of patients who underwent intravitreal injections from November 2009 to May 2013 at Sultan Qaboos University Hospital. RESULTS: Throughout a period of 42 months, a total of 711 intravitreal injections were performed. That included 214 patients (275 eyes). Around one-third of the eyes received two injections or more. The injected agents were bevacizumab (59.8%), ranibizumab (32.3%), triamcinolone (7.5%), and very few patients with endophthalmitis received intravitreal antibiotics and antifungal agents. The three most common indications for the injection therapy were diabetic macular edema (50.9%), choroidal neovascularization (24.3%), and retinal vein occlusive diseases (11.5%). Serious adverse events were rare, and they occurred as ocular (0.9% per patient) and systemic (3.3% per patient). There were 42 eyes received intravitreal triamcinolone, and 24% of them developed intraocular hypertension that required only medical treatment. CONCLUSION: Different intravitreal agents are currently used to treat many ocular diseases. Currently, therapy with intravitreal agents is very popular, and it carries a promising outcome with more efficiency and safety. PMID- 26903723 TI - Indications and outcomes of scleral buckle removal in a tertiary eye care center in South India. AB - PURPOSE: To study the clinical profile of patients undergoing scleral buckle removal (SBR) surgery. MATERIALS AND METHODS: All consecutive patients undergoing SBR surgery following scleral buckle for retinal detachment repair between January 2002 and December 2011 with a minimum postSBR follow-up of 6 months were included in this study. A record based on analysis of indications, methods, complications, and outcomes of the eyes was performed. RESULTS: One hundred and two eyes of 101 patients (men = 77; 76.24% and women = 24; 23.76%) belonging to the age group of 15-78 years (mean 50 +/- 15 years) were included in this study. Time gap between scleral buckle and SBR ranged from 2 to 216 months (mean 61 +/- 51 months). Buckle exposure with clinical infection (81; 79.41%) was the most common indication. Of 90 (88.2%) eyes with positive culture, 75 (83.3%) revealed single and 15 (16.6%) revealed multiple microorganisms. Staphylococcus epidermidis (42; 41.2%), was the most common isolate. Fungus was isolated in 3 (2.94%) eyes. Globe perforation (14; 13.7%) and recurrent retinal detachment (7; 6.9%) were the commonest complications. Time gap between SBR and recurrent retinal detachment ranged from 15 days to 50 months (mean 12.2 +/- 18.3 months). CONCLUSIONS: Most of the exposed scleral buckles developed clinical infection few months to years after surgery, ultimately requiring SBR. Recurrent retinal detachment after SBR may appear from few days to years later warranting a long term follow-up. PMID- 26903724 TI - Conventional extracapsular cataract extraction and its importance in the present day ophthalmic practice. AB - PURPOSE: A retrospective study aimed to evaluate high risk cases where conventional Extracapsular cataract extraction (ECCE) was performed, their intra operative and post-operative outcomes. SETTING: Sri Srinivasa Sankara Nethralaya (Tirupati) Tirumala Tirupati Devastanams Central Hospital, Tirupati, India. SUBJECTS AND METHODS: Retrospective study of 207 patients who underwent ECCE at the hospital between august 2010 to June 2012. Operative data included details like grade of risk, intra and postoperative complications and visual outcome. RESULTS: Out of 207 cases, 188 were in group 3 (moderate risk, 3-5 points) and 19 in group 4 (high risk, 6 points or more). The intra operative complications in group 3 were 8 (0.042%) and none in group 4. Final best corrected visual acuity (BCVA) of 6/12 and more were 184 (88.88%). Final refraction of less than 2.0 astigmatism was seen in 80.19% (n=166). CONCLUSION: Segregation of cases depending on the risk factors can lead to lower intra operative complications and therefore good postoperative outcome. We believe that phacoemulsification, manual small incision cataract surgery (MSICS) and ECCE each has its own importance and should be used as per the cataract with risk factors. PMID- 26903725 TI - Isolated abducens nerve palsy after closed head injury in a child. AB - The authors present the rare case of a 5-year-old child with an isolated right abducens nerve palsy following a minor closed head injury. Occlusion of the left eye for 4 h daily was prescribed, and the child remained under close ophthalmological follow-up. Significant improvement was noticed in the following 6 months. PMID- 26903726 TI - Dual intravitreal foreign body: Intravitreal cilia in penetrating injury. AB - Intraocular cilia, though a rare condition, has been previously reported in cases of open globe injury. We discuss a unique case of intravitreal cilia, found incidentally during vitrectomy for intravitreal foreign body removal. PMID- 26903727 TI - A rare case of delayed onset capsular block syndrome managed using 25-gauge vitrector. AB - We report a case of delayed onset capsular block syndrome in a patient 6 years after undergoing cataract surgery. Ocular examination revealed marked diminution of vision accompanied with a collection of milky fluid between the intraocular lens and posterior capsule. To treat and to understand the pathology of the condition, aspiration of fluid using 25-gauge vitrector through pars plana was done, and contents sent for microbiological analysis which did not reveal any growth. Postoperative period was uneventful with the absence of intraocular inflammation and excellent visual recovery. PMID- 26903729 TI - Dome-shaped macula simulating choroidal hemangioma in a myopic patient. AB - To describe a case of dome-shaped macula simulating a choroidal hemangioma and discuss multimodal imaging features to distinguish between these disorders. A 52 year-old myopic male with a refraction of -8.00 D in both eyes developed blurred vision in the left eye OS) over 4 years. Fundus examination of the right eye (OD) was unremarkable. In OS, there was a subtle orange-colored mass in the macular region with subretinal fluid, suggestive of choroidal hemangioma. Upon referral, our examination disclosed an echodense mass on ultrasonography of OS, measuring 1.0 mm thickness, and additional staphyloma was noted. Enhanced depth imaging optical coherence tomography (EDI-OCT) confirmed subfoveal fluid over a dome shaped mass that originated in the sclera and not the choroid, consistent with the dome-shaped macula. The OD showed similar features, but to a lesser degree. Both eyes demonstrated choroidal thinning on EDI-OCT, related to high myopia. Dome-shaped macula can masquerade as choroidal hemangioma, especially when associated with subretinal fluid. In these cases, EDI-OCT can document "tumor" origin from within the sclera and not the choroid. PMID- 26903728 TI - Anti-vascular endothelial growth factors for choroidal neovascularization secondary to choroidal osteoma: Long-term results. AB - Choroidal osteoma is an uncommon benign osseous intraocular tumor typically seen unilaterally in young women. Visual loss can occur due to choroidal neovascularization (CNV) complicating osteoma. We report a rare case of bilateral choroidal osteoma with secondary CNV in a young male and the long-term results following anti-vascular endothelial growth factor (VEGF) therapy. A 30-year-old male with history of defective vision in both eyes since several years and recent worsening in the right eye (RE) since 2 months was found to have bilateral macular osteoma with CNV in the RE based on clinical evaluation, fluorescein angiography, optical coherence tomography, and ultrasonography. Intravitreal injection of ranibizumab at monthly intervals for three doses resulted in resolution of CNV and remained stable for 5 years. Recurrent CNV detected 6 years later responded to an injection of intravitreal bevacizumab and has remained stable till date. Anti-VEGF therapy stabilized the secondary CNV in our patient for 7 years with satisfactory structural and functional outcome, demonstrating the long-term efficacy of this modality of treatment. PMID- 26903730 TI - Propranolol therapy in a case of capillary hemangioma. AB - Capillary hemangioma is one the most common tumors of eyelid and orbit reported in pediatric age group. Oral propranolol therapy is latest addition to the armamentarium of treatment options available to ophthalmologists in treating capillary hemangiomas. We report the successful response to propranolol therapy to a 5-year-old child with capillary hemangioma involving lids, orbit, and the paranasal sinuses. A long-term follow-up is necessary for the prognostic efficacy of the therapy. PMID- 26903731 TI - Microphthalmos, orbital cyst, and missing thumbs: A rare case report. AB - A 5-month-old girl was presented to us with a right orbital cyst covering a microphthalmic eye, absent digits (thumbs) in both hands, and absence of right radius and left kidney. The hematological profile of the patient was within normal limits. The patient had a family history of leukemia and the chromosomal analysis was suggestive of Fanconi's anemia (FA). The cyst was excised in toto and sent for histopathology. To the best of our knowledge, this is the first case report of an orbital cyst covering a microphthalmic eye in a patient with FA. This case report also stresses the fact that FA can be missed by ophthalmologists in the patients with congenital microphthalmos and missing thumbs and efforts should be made to avoid doing so. PMID- 26903732 TI - Delayed sclerotomy wound dehiscence after lensectomy and vitrectomy in Marfan syndrome. AB - Marfan syndrome (MFS) is associated with abnormal fibrillin development that can cause morbidity and mortality. A case of acute onset hypotony due to sclerotomy wound dehiscence 13 years after 20-gauge pars plana vitrectomy and lensectomy is reported in a patient with MFS. Slit lamp examination revealed a leaking sclerotomy wound and intraoperatively the source was noted to be the prior sclerotomy site. On postoperative follow-up, the patient's vision returned to baseline, and intraocular pressure normalized. Twenty-gauge sclerotomy wound dehiscence may occur years after surgery, especially in patients with abnormal collagen as in MFS. PMID- 26903733 TI - Scleral necrosis in congenital erythropoietic porphyria: A case report and review of the literature. AB - A 28-year-old presented with complaints of severe pain and redness in the left eye since 2 weeks. He had similar complaints in the right eye 2 years back for which he had undergone a scleral patch graft. Best corrected visual acuity was 20/20 in both eyes. The right had a well vascularized scleral graft and rest of the anterior segment was normal. The left eye had inferior conjunctival congestion with an area of the scleral melt with uveal show just temporal to the limbus in the interpalbebral area. The cornea was clear and anterior chamber was quiet in the left eye. Applanation tonometry and fundus evaluation were normal in both eyes. Physical examination revealed hyperpigmented skin lesion, hypertrichosis and absorption of distal phalanges. Laboratory, ocular and physical findings confirmed the diagnosis of congenital erythropoietic porphyria. He was on oral steroids 40 mg/day since 2 weeks and topical antibiotics and lubricants. He was advised to continue the same and was taken up for scleral patch graft with fibrin glue in the left eye. Postoperatively he was continued on topical and oral steroids and lubricants.3 weeks later the left eye had stabilized however patient came with a melt in the right eye. Since it was an early melt, we went ahead with cyanoacrylate glue and bandage contact lens in the right eye and started him on topical steroids for the right eye also. Three months later both the eyes were stable, and the patient was gradually tapered off the steroids. PMID- 26903734 TI - Peripheral ulcerative keratitis associated with chronic malabsorption syndrome and miliary tuberculosis in a child. AB - A 16-year-old girl presented with pain, redness, watering, and blurring of vision in her right eye. Slit lamp examination revealed the presence of peripheral ulcerative keratitis (PUK) and nodular scleritis. On clinical examination, the patient had stunted growth, low body mass index, and enlarged axillary nodes. Giardia cysts were present in the stool sample and histopathology of axillary lymph nodes showed caseating necrosis suggestive of tuberculosis (TB). A diagnosis of PUK with chronic malabsorption syndrome secondary to giardiasis and miliary TB was made. Oral metronidazole, anti-tubercular treatment, high protein diet and vitamin supplements were started. Topical steroids were started for peripheral ulcerative lesions following, which the PUK resolved. PMID- 26903736 TI - Rapidly reversible visual loss in posterior reversible encephalopathy syndrome: An ophthalmologist's enigma. AB - Posterior reversible encephalopathy Syndrome (PRES) may present with a sudden onset reversible visual loss under special visual conditions. Such patients' may initially be misdiagnosed as Malingering. Ophthalmologists may be the first physicians to be confronted by such patients. Hence, a knowledge of this condition is vital to diagnosis and management of such conditions. PMID- 26903735 TI - Pulsatile enophthalmos, severe esotropia, kinked optic nerve and visual loss in neurofibromatosis type-1. AB - Neurofibromatosis Type I if associated with aplasia of greater wing of sphenoid may be associated with a pulsatile exophthalmos. However, very rarely it may be associated with a pulsatile enophthalmos. This clinical image describes a rare presentation with pulsatile enophthalmos, esotropia and kinking of the optic nerve due to neurofibomatosis type I. PMID- 26903737 TI - High altitude subhyaloid hemorrhage. AB - Subhyaloid hemorrhages can occur as a result of exposure to high altitude. We hereby report a clinical picture of subhyaloid hemorrhage associated with high altitude. The case demonstrates optical coherence tomography findings that aid diagnosis of subhyaloid hemorrhage. PMID- 26903738 TI - Nonprogressive, bilateral painless swellings of the lacrimal glands. PMID- 26903739 TI - Necrotizing scleritis in a case of Vogt-Koyanagi-Harada disease. PMID- 26903740 TI - Stiffened hang-back: A suggested modification using cyanoacrylate glue. PMID- 26903741 TI - A fellow's life. PMID- 26903742 TI - Is Early Onset Androgenic Alopecia a Marker of Metabolic Syndrome and Carotid Artery Atherosclerosis in Young Indian Male Patients? AB - BACKGROUND: Androgenic alopecia (AGA) is a common cosmetically and psychosocially distressing condition. High androgen level contributes to the development of atherosclerosis, thrombosis leading to hypertension and hypercholesterolemia. OBJECTIVES: To study the clinico-epidemiological profile of AGA and the presence of metabolic syndrome (MetS) and carotid artery atherosclerosis in male patients with early onset AGA as compared to controls. MATERIALS AND METHODS: In this case control study, 100 male patients of age 18-35 years with AGA and an equal number of age-matched healthy controls attending skin and STD OPD were included. Assessment of the degree of hair loss, evaluation of MetS and carotid artery color Doppler for the atherosclerotic plaque was done in all patients. RESULTS: Statistically significant number of patients with early onset AGA 22/100 (22%) (P < 0.05) fulfilled the criteria for MetS compared to 8/100 (8%) in the control group. There were statistically significant differences in mean values of waist circumference, serum triglycerides, serum cholesterol, systolic blood pressure, diastolic blood pressure, fasting glucose concentration, and very low-density lipoprotein (LDL). However, no significant differences were observed in the mean values of high-density lipoprotein cholesterol and LDL cholesterol. The atherosclerotic plaque was found in two patients of the study group, and no plaque was found in control patients. CONCLUSION: We suggest that all men with AGA should be thoroughly investigated, and lifestyle changes should be started in the early period of life so as to reduce the risk of various problems associated with MetS. AGA can be considered as an early marker for MetS. PMID- 26903743 TI - Comparative Evaluation of Intralesional Triamcinolone Acetonide Injection, Narrow Band Ultraviolet B, and their Combination in Alopecia Areata. AB - CONTEXT: Alopecia areata (AA), an autoimmune disorder, can affect any hair bearing area. No treatment so far has produced a consistent response. Narrow band ultraviolet B (NBUVB) has not been studied in its management. AIMS: Comparative evaluation of intralesional triamcinolone acetonide injection, NBUVB, and their combination in AA. MATERIALS AND METHODS: Forty patients (28 males and 12 females) with at least three patches of hair loss were enrolled after obtaining written informed consent. Patches were subdivided as follows: Patch 1 was injected with triamcinolone acetonide 2.5 mg/ml (total of three injections) at 3 weeks interval. Patch 2 - NBUVB was given twice a week for a total of 12 weeks. Patch 3 - combination of injection and NBUVB. Therapeutic response was recorded as regrowth of terminal hair (G0 to G4). STATISTICAL ANALYSIS USED: Chi-square test. P < 5% was considered significant. RESULTS: At the end of treatment and follow-up, that is, at week 12, more than 50% of hair regrowth was evident in 27 (67.5%) patients with intralesional steroid; 7 (17.5%) with NBUVB; and 25 (62.5%) patients with their combination. This difference in the clinical response was statistically significant. CONCLUSIONS: Intralesional steroid is more effective than NBUVB and their combination is not synergistic in terms of the clinical response in AA. PMID- 26903745 TI - Multiple Trichilemmal Cysts of the Scalp in a Young Male. AB - Trichilemmal cyst (TC) is a benign cyst and is lined by stratified squamous epithelium that is derived from the outer root sheath. Middle-aged females are more commonly affected. It has close resemblance to epidermoid cyst and hence should be differentiated. We report a case of painful multiple TC on the scalp in a young male where a skin punch has been used as a therapeutic method. PMID- 26903744 TI - A Marine Protein-based Dietary Supplement for Subclinical Hair Thinning/Loss: Results of a Multisite, Double-blind, Placebo-controlled Clinical Trial. AB - INTRODUCTION: Since skin and hair quality are potent vitality signals, and hair growth deficiency can cause significant psychological morbidity. In addition to clearly-defined hair loss disorders, milder forms of hair thinning or hair loss appear to be increasingly common, with a suggestion that sub-optimal diets and stressful lifestyles may be involved. METHODS: Here we assess the value of a dietary marine-extract based dietary supplement in premenopausal women with subclinical hair thinning or hair loss conditions. This multi-site, randomized double-blind, placebo-controlled clinical trial was conducted with impact on hair shedding rate and hair fiber diameter (assessed by phototrichogram) as primary end points upon consumption of the oral supplement compared to a placebo. A total of 96 eligible female subjects were enrolled aged 21-55 years of age from Asian, Caucasian, and Hispanic ethnic backgrounds. RESULTS: This study showed that hair shedding was significantly reduced in the first 3-6 months of daily consumption of the oral supplement. Moreover, phototrichogram image analysis revealed a statistically significant increase in the mean vellus-like hair diameter after 6 months of supplement consumption, when compared to the mean vellus-like hair diameters measured at baseline. DISCUSSION: These results support the view that a nutritional supplement approach may be useful for women in this age group to deal with subclinical hair thinning or hair loss conditions, and those components of this marine extract-based oral supplement may be a useful adjunct. PMID- 26903746 TI - Sebaceous Hyperplasia Mimicking Linear Wart over Ear. AB - Sebaceous hyperplasia (SH), a common, benign condition of sebaceous gland, presents most commonly over face. Lesions are usually described as asymptomatic, soft, discrete, and yellow with a surface that ranges from smooth to slightly verrucous. The pathogenesis is not fully understood. It does not require treatment, but many time lesions can be cosmetically unfavorable than, need to be destroyed or excised. A case of 23-year-old male presenting with the skin colored to hyperpigmented linear hyperkeratotic plaque mimicking a wart, over the right ear is presented here, which was diagnosed as SH. PMID- 26903747 TI - Perifolliculitis Capitis Abscedens et Suffodiens in a 7 Years Male: A Case Report with Review of Literature. AB - Perifolliculitis capitis abscedens et suffodiens is the least common of the three conditions included in the follicular occlusion triad. It is one of the causes of scarring alopecia in adult males. Clinically it has to be differentiated from other causes of folliculitis affecting the scalp. The histopathology is diagnostic. The treatment is prolonged and the clinical course is characterized by remissions and relapses. PMID- 26903748 TI - Alopecia in Systemic Amyloidosis: Trichoscopic-Pathologic Correlation. AB - Alopecia in systemic amyloidosis is very rare and has been described as individual cases of diffuse nonscarring alopecia and a case of alopecia universalis. We report the trichoscopic findings in alopecia associated with systemic amyloidosis. The most prominent feature was a salmon colored halo (0.3-1 mm in diameter) surrounding the follicular ostia. Other features included broken hairs and black dots. The salmon colored halo correlated on pathology with the perifollicular deposition of amyloid. The horizontal sections showed that the sebaceous glands were preserved which supports the nonscarring pattern of the alopecia. PMID- 26903749 TI - An Unusual Location of a Pilar Sheath Acanthoma. AB - Pilar sheath acanthoma is a rare, benign follicular hamartoma. Mehregan and Brownstein fist reported this solitary, asymptomatic, and skin-colored nodule with a central pore-like opening in 1978. The classic location for these lesions is the upper lip of elderly patients. Here we report an interesting case of a pilar sheath acanthoma presenting on the left eyebrow in a middle-aged female. To our knowledge, this is the first reported case of a pilar sheath acanthoma in such a unique location. PMID- 26903750 TI - Generalized Hypertrichosis Induced by Topical Minoxidil in an Adult Woman. AB - Hypertrichosis is a common side effect of topical minoxidil and has been reported to occur mainly close to the areas of application. In this paper, we present a case of a 26-year-old woman who developed generalized hypertrichosis 8 weeks after treatment with 5% topical minoxidil solution for alopecia areata. Generalized hypertrichosis is a rare side effect and has been described mainly in children and adolescents. Even though minoxidil is commonly prescribed for alopecia areata, there is insufficient evidence to support its systematic use and the occurrence of adverse effects should prompt drug interruption. Nonetheless, topical minoxidil has been shown to be a safe medication for adult patients, and we believe that the present case was an isolated one, possibly resulting from the misuse of the drug. PMID- 26903751 TI - Patchy Traction Alopecia Mimicking Areata. AB - Acute traction alopecia is a diagnostic challenge when the external factor is not suspected or admitted. We report two female patients with non-scarring patchy alopecia resulting from traction of video-electroencephalogram electrodes in which the clinical diagnosis of alopecia areata was suspected. Associated diffuse hair disorders might be implicated in these cases. The correct diagnosis of traction alopecia is important in order to avoid unnecessary treatments. PMID- 26903752 TI - Pilar Sheath Acanthoma Presenting as a Nevus. PMID- 26903754 TI - The effect of mobile phone short messaging system on healthy food choices among Iranian postmenopausal women. AB - INTRODUCTION: Central adiposity and metabolic syndrome are quite common among postmenopausal women. Dietary diversity and healthy food choices have essential role in health and also in prevention of obesity. The main objective of this study was to evaluate the impact of mobile phone short messaging system on healthy food choices among Iranian postmenopausal women. MATERIALS AND METHODS: This was a randomized controlled trial in which 100 postmenopausal women aged 40 60 years were recruited and assigned to two groups (50 each in the intervention and control groups). Food frequency consumption was measured using a questionnaire. A total of 16 text messages including information about modification of food selection (healthy choices, benefits, methods, etc.,) were sent to participants in the intervention group during 4 months follow-up (1/week). The Chi-square and independent t-test used for data analysis. Ninety two women completed the study. RESULTS: The consumption of Vitamin A rich fruits and vegetables significantly increased in the intervention group compared to the control group (P < 0.001). More women in the intervention group consumed fish after intervention (P = 0.02). The consumption of green leafy vegetables showed a nonsignificant increase in the intervention group. CONCLUSION: Using mobile phone short messaging system can improve the healthy food choices regarding Vitamin A rich fruits and vegetables and fish among postmenopausal women. PMID- 26903753 TI - Premature ovarian insufficiency: Pathogenesis and management. AB - The term premature ovarian insufficiency (POI) describes a continuum of declining ovarian function in a young woman, resulting in an earlier than average menopause. It is a term that reflects the variable nature of the condition and is substantially less emotive than the formerly used "premature ovarian failure" which signaled a single event in time. Contrary to the decline in the age of menarche seen over the last 3-4 decades there has been no similar change in the age of menopause. In developed nations, the average age for cessation of menstrual cycles is 50-52 years. The age is younger among women from developing nations. Much has been written about POI despite a lack of good data on the incidence of this condition. It is believed that 1% of women under the age of 40 years and 0.1% under the age of 30 years will develop POI. Research is increasingly providing information about the pathogenesis and treatments are being developed to better preserve ovarian function during cancer treatment and to improve fertility options. This narrative review summarizes the current literature to provide an approach to best practice management of POI. PMID- 26903755 TI - Histopathology findings in patients presenting with menorrhagia: A study of 100 hysterectomy specimen. AB - BACKGROUND: Menorrhagia, by definition, is heavy cyclical blood loss in excess of 80 ml/month of menstrual period lasting longer than 7 days. There are many possible causes of heavy menstrual bleeding which include hormonal imbalance, fibroids, miscarriage or ectopic pregnancy, nonhormonal intrauterine device, adenomyosis, pelvic inflammatory disease, and rarely uterine, ovarian, or cervical cancer. Treatment depends on the causes of the menorrhagia. Hysterectomy is one of the several surgical procedures as definitive treatment. OBJECTIVE: To determine the histopathologic spectrum of lesions associated with menorrhagia in different age groups. STUDY DESIGN: This prospective descriptive study was conducted at the Department of Pathology, People's College of Medical Sciences and Research Centre, Bhopal. During the study period, 100 hysterectomy specimens were taken which were performed for the treatment of menorrhagia. Patients with menorrhagia in the age group of 30-50 years were selected after detailed history and fulfilling the inclusion criteria. RESULT: In our study, it was observed that maximum number of cases were in the age group of 41-50 years (n = 35) followed by the age group of 31-40 (n = 30). Out of 100 cases, 31% cases (n = 31) showed adenomyosis followed by leiomyomas 25% (n = 25), endometrial hyperplasia 23% (n = 23), and endometrial polyp 4% (n = 4). 11% cases (n = 11) showed dual pathology consisting of both adenomyosis and endometrial hyperplasia and 6% cases (n = 6) of leiomyoma with adenomyosis. CONCLUSION: Uterine adenomyosis and leiomyoma are the most common benign conditions found in hysterectomy specimens with peak incidence at 31-50 years. Patients having menorrhagia above 40 years should be screened for any endometrial pathology. Histopathology is mandatory for confirming diagnosis and the key to effective therapy and optimal outcome. PMID- 26903756 TI - Correlation between anthropometry and lipid profile in healthy subjects of Eastern India. AB - BACKGROUND: Cardiovascular diseases constitute one class of common contributors to morbidity and mortality worldwide. Prevalence of overweight and obesity has dramatically increased in developing countries and is related to cardiovascular risk factors. Anthropometric parameters have the advantages in daily clinical practice of being a simple to measure tool with good reproducibility, especially in a developing country like India. Aim of this study is to correlate some anthropometric variables with lipid parameters in healthy subjects and to assess the anthropometric variable which best reflects the altered lipid profile. MATERIALS AND METHODS: A hospital based cross-sectional study was conducted after the Institutional Ethical Committee Clearance. Included participants (1187) were subjected to anthropometric measurements such as height, weight, waist circumference (WC), and hip circumference using standard procedures on the same morning of the day, as the blood sample was collected after overnight fast and estimated for fasting blood sugar and lipid profile. RESULTS: There is a weak correlation between body mass index (BMI) and lipid parameters. Among all the anthropometric variables studied, WC is best correlated to lipid parameters. The mean values of lipid parameters were not significantly different in BMI <25 and BMI >=25 groups. CONCLUSIONS: WC remains one of the simple and reliable variables which best reflects the lipid profile. In a developing country like India, where measurement of cardiovascular risk factors such as body fat saturation and lipid profile remains difficult in the rural population, WC may be used as an effective tool, without being used as a substitute. PMID- 26903757 TI - Clinical outcome of abdominal sacrocolpopexy. AB - INTRODUCTION: Vaginal vault prolapse is one of the distressing conditions which occur after hysterectomy. This is due to the weakness or detachment of sacrouterine cardinal ligament complex from the vaginal cuff. Till now, the most accepted procedure for this condition is sacrocolpopexy. MATERIALS AND METHODS: We present a cohort of patients who underwent abdominal sacrocolpopexy (ASC) from April 2009 to August 2013. These patients were followed till April 2014 and were evaluated for subjective and objective outcomes following ASC. RESULTS: One patient had intraoperative hemorrhage and postoperative hematoma formation. One patient had vault abscess which was managed conservatively. Hundred percent success rate was noted at 1 year. Long-term patient satisfaction score was 85 (70 90). PMID- 26903758 TI - Evaluation of body esteem and mental health in patients with breast cancer after mastectomy. AB - INTRODUCTION: Mastectomy in patients with breast cancer can severely affect their body esteem. It also changes the emotions and attitudes of patients toward their body and causes psychological reactions such as depression, anxiety, and stress. AIMS: This study was conducted with the aim of assessing correlation between body esteem and mental health in patients with breast cancer after mastectomy. MATERIALS AND METHODS: This study is a descriptive study. One hundred patients with breast cancer after mastectomy were selected by convenience sampling from Seyed Al Shohada Hospital in Isfahan. Data gathering tools were questionnaires of body esteem and SCL-25 mental health and were analyzed by SPSS-PC (v.17). RESULTS: According to the score of body esteem (2.80) and the overall average score for body esteem (36.46), patients had low body esteem. About dimensions of the mental health, the highest average was associated with depressive disorders. According to the results of the Spearman correlation coefficient, there was a direct linear relationship between body esteem and mental health. CONCLUSION: Considering the impact of mastectomy on body esteem and mental health and the relationship between the variables, nurses take steps for identifying and referring patients to the counseling centers to prevent psychological disorder aspects. PMID- 26903759 TI - Epithelial ovarian tumors: Clinicopathological correlation and immunohistochemical study. AB - BACKGROUND: Ovarian cancer is the third leading site of cancer among women, trailing behind cervix and breast cancer. AIM: This study was undertaken to analyze the immunohistochemical (IHC) profile of estrogen receptors (ER), progesterone receptors (PR), Ki-67, and p53 in various ovarian epithelial tumors and attempt correlation with clinical and histopathological findings. MATERIALS AND METHODS: The present study was conducted over a period of 4 years. A technique of manual tissue array was employed for cases subjected for IHC. The primary antibodies used were ER, PR, p53, and Ki-67. A correlation was attempted between histopathological and IHC findings. Results were subjected to statistical analysis. Software program "the primer of biostatistics 5.0" was used for calculation of interrelationships between the analyzed ER, PR, p53, and Ki-67 expression and histological factors by Pearson's Chi-square test. The results were considered to be significant when the P < 0.05. RESULTS: There were 110 cases of surface epithelial ovarian tumors (SEOT) encountered over the period of 4 years. The expression of ER was more in malignant tumors (13/16, 81.25%) than borderline (9/12, 75%) and benign (20/82, 24.39%). As compared to ER, the expression of PR was more in benign (51/82, 62.19%) than borderline (8/12, 66.67%) and malignant tumors (9/16, 56.25%). The expression of PR was more in benign tumors than borderline and malignant tumors. However, this was not statistically significant (Chi-square = 0.335 with 2 degrees of freedom; P = 0.846). The expression of p53 was less in benign (5/82, 6.1%) than borderline (9/12, 75%) and malignant tumors (13/16, 81.25%). The expression of Ki-67 was more in malignant (4/82, 4.88%) than borderline (10/12, 83.33%) and benign tumors (15/16, 93.75%). In all the above cases, the difference was statistically significant (P < 0.05). There was statistically significant difference in the expression of ER, PR, p53, and Ki-67 in the patients with age <40 years and above 40 years (P = 0.912). A positive correlation was observed in p53 expression and tumor grade. Similar correlation was seen in Ki-67 and tumor grade. It was also noted that mean Ki-67 labeling index (Li) had also increased with tumor grade. In the case of serous tumors, ER was expressed in all high- and low-grade tumors. The expression of PR was more in low-grade tumors than high-grade ones. P53 expression was seen in all high-grade tumors and 33.34% of low-grade tumor. The Ki-67 Li was more in high-grade tumors than low-grade tumors. Expression of ER, p53, and Ki-67 was higher in tumor showing metastasis. The mean Ki-67 Li was also higher in metastasizing tumors. However, PR expression was less in metastasizing tumors than nonmetastasizing tumors. CONCLUSION: IHC marker report of ER, PR status, and Ki-67 if included in each pathology report will pave the way for better understanding of biological behavior and modify treatment strategies. PMID- 26903760 TI - Mouth on fire: Oral discomfort in postmenopausal women may be surprising!! PMID- 26903761 TI - Posterior vaginal wall Gartner's duct cyst. AB - Cyst of posterior vaginal wall is very rare. This case relates to a patient who presented with polypoidal mass protruding out from vagina which could have been easily mistaken as uterovaginal prolapse, but appropriate clinical evaluation supported with investigations clinched the diagnosis easily. PMID- 26903762 TI - Influenza Illness in Pregnant Indian Women: A Cross-Sectional Study. AB - Data about burden of influenza in pregnancy in India are scant. In order to assess the contribution of influenza to acute respiratory illness (ARI) in pregnancy, 266 north Indian pregnant females with febrile ARI were studied from December 2014 to May 2015. Twin nasopharyngeal/oropharyngeal swabs were obtained and tested for influenza viruses by RT-PCR. Fifty (18.8%) patients tested positive for influenza (A/H1N1pdm09 in 41, A/H3N2 in 8, and influenza B Yamagata in 1). Rigors, headache, and a family history of ARI were significantly more frequent in influenza positive patients. Oseltamivir and supportive therapy were administered to all confirmed cases. Nine influenza positive cases needed hospitalization for their respiratory illness, and 5 developed respiratory failure. Of these, 4 (3 in third trimester) succumbed to their illness. We conclude that influenza viruses are a cause of significant morbidity and mortality among pregnant females with ARI in north India. As such, appropriate preventive strategies of influenza vaccination and early initiation of antiviral therapy during illness are stressed. PMID- 26903764 TI - Stability of chronic medicines in dosage administration aids. How much have been done? AB - BACKGROUND: The prevalence of chronic diseases is increasing in Asia, therefore compliance to the medications is of utmost importance to slow disease progression and improve outcomes. Dosage administration aids (DAAs) serve as important tool to improve the compliance of patients. However, there is a dearth of data on the stability of chronic medications in DAAs. Furthermore, data presented by our Western counterparts may not be applicable to us because of our extreme humidity and temperature. In this study, we aim to summarize the data available in the literature on the stability of chronic medications in DAA. METHODS: We performed a literature search using electronic databases and related keywords. RESULTS: In total, 24,336 articles were retrieved and 21 articles were found to be relevant to our topic. This commentary stratified drugs according to their treatment categories and key stability conclusions, DAA and conditions used and recommendations were presented. CONCLUSION: Due to the lack of specific data, pharmacists have to exercise their professional judgment with the help from professional guidelines when using DAA in repackaging medication. Manufacturers and regulators can play a greater role in filling the gap needed to provide pharmacists with necessary information to fulfill their function. PMID- 26903765 TI - Patient adherence to warfarin therapy and its impact on anticoagulation control. AB - Warfarin is a commonly prescribed oral anticoagulant in Saudi Arabia and yet patient adherence to warfarin therapy and its impact on anticoagulation control have not been well researched here. A cross-sectional survey was conducted over 6 weeks at the outpatient anticoagulant clinic on patients who were receiving warfarin. Adherence was assessed using the translated Arabic version of the Morisky Medication Adherence Scale (MMAS-8). Levels of adherence were classed as low (score ? 7), or high (score = 8) based on the scores. Good anticoagulation control was defined as percent Time INR in Therapeutic Range (TTR) ? 75% using the Rosendaal method. A total of 192 patients completed a questionnaire with a response rate of 68.1%. It was established that no association was found between adherence to warfarin therapy and INR control groups. Among the 89 (46.4%) patients who had high adherence, only 34 (38.2%) had an acceptable INR control. This was versus 103 (53.6%) patients who had low adherence but also 34 (33.0%) had good INR control. Multivariate logistic regression (MLR) analysis showed that when studying females and occupational status of unemployment, they were independently associated with poor INR control with an OR 2.31, 95% CI 1.10-4.92, and OR 2.71, 95% CI 1.12-6.61 respectively. MLR analysis also showed that age <50 years alongside no formal education was independently associated with low adherence to warfarin therapy with an OR 2.67, 95% CI 1.29-5.52 and OR 2.63, 95% CI 1.01-6.93 respectively. The demographic background influences adherence and INR control, but no association was found between adherence and anticoagulation control. PMID- 26903763 TI - Biomedical microelectromechanical systems (BioMEMS): Revolution in drug delivery and analytical techniques. AB - Advancement in microelectromechanical system has facilitated the microfabrication of polymeric substrates and the development of the novel class of controlled drug delivery devices. These vehicles have specifically tailored three dimensional physical and chemical features which together, provide the capacity to target cell, stimulate unidirectional controlled release of therapeutics and augment permeation across the barriers. Apart from drug delivery devices microfabrication technology's offer exciting prospects to generate biomimetic gastrointestinal tract models. BioMEMS are capable of analysing biochemical liquid sample like solution of metabolites, macromolecules, proteins, nucleic acid, cells and viruses. This review summarized multidisciplinary application of biomedical microelectromechanical systems in drug delivery and its potential in analytical procedures. PMID- 26903767 TI - Impact of a pharmacist led diabetes mellitus intervention on HbA1c, medication adherence and quality of life: A randomised controlled study. AB - Malaysia is situated in Western Pacific region which bears 36.17% of total diabetes mellitus population. Pharmacist led diabetes interventions have been shown to improve the clinical outcomes amongst diabetes patients in various parts of the world. Despite high prevalence of disease in this region there is a lack of reported intervention outcomes from this region. The aim of this study was to evaluate the impact of a pharmacist led intervention on HbA1c, medication adherence, quality of life and other secondary outcomes amongst type 2 diabetes patients. METHOD: Type 2 diabetes mellitus patients (n = 73) attending endocrine clinic at Universiti Kebangsaan Malaysia Medical Centre (UKMMC) were randomised to either control (n = 36) or intervention group (n = 37) after screening. Patients in the intervention group received an intervention from a pharmacist during the enrolment, after three and six months of the enrolment. Outcome measures such as HbA1c, BMI, lipid profile, Morisky scores and quality of life (QoL) scores were assessed at the enrolment and after 6 months of the study in both groups. Patients in the control group did not undergo intervention or educational module other than the standard care at UKMMC. RESULTS: HbA1c values reduced significantly from 9.66% to 8.47% (P = 0.001) in the intervention group. However, no significant changes were noted in the control group (9.64-9.26%, P = 0.14). BMI values showed significant reduction in the intervention group (29.34 28.92 kg/m(2); P = 0.03) and lipid profiles were unchanged in both groups. Morisky adherence scores significantly increased from 5.83 to 6.77 (P = 0.02) in the intervention group; however, no significant change was observed in the control group (5.95-5.98, P = 0.85). QoL profiles produced mixed results. CONCLUSION: This randomised controlled study provides evidence about favourable impact of a pharmacist led diabetes intervention programme on HbA1c, medication adherence and QoL scores amongst type 2 diabetes patients at UKMMC, Malaysia. PMID- 26903766 TI - Blood glucose control for patients with acute coronary syndromes in Qatar. AB - BACKGROUND: Blood glucose is known to be elevated in patients presenting with acute coronary syndromes. However a gap in knowledge exists regarding effective management strategies once admitted to acute care units. It is also unknown what factors (if any) predict elevated glucose values during initial presentation. OBJECTIVES: OBJECTIVES of the study were to characterize blood glucose control in patients admitted to the cardiac care unit (CCU) in Qatar and to determine predictive factors associated with high glucose levels (>10 mmol/l) on admission to the CCU. SETTING: All data for this study were obtained from the CCU at Heart Hospital in Doha, Qatar. METHOD: A retrospective chart review was completed for patients admitted to the CCU in Qatar from October 1st, 2012 to March 31st, 2013, of which 283 were included. Baseline characteristics (age, gender, nationality, medical history, smoking status, type of acute coronary syndrome), capillary and lab blood glucose measurements, and use of insulin were extracted. Time spent in glucose ranges of <4, 4 to <8, 8 to <10, and >10 mmol/1 was calculated manually. Univariate and multivariate logistic regression were performed to assess factors associated with high glucose on admission. The primary analysis was completed with capillary data and a sensitivity analysis was completed using laboratory data. MAIN OUTCOME MEASURE: Blood glucose values measured on admission and throughout length of stay in the CCU. RESULTS: Capillary blood glucose data showed majority of time was spent in the range of >10 mmol/l (41.95%), followed by 4-8 mmol/l (35.44%), then 8-10 mmol/l (21.45%), and finally <4 mmol/l (1.16%). As a sensitivity analysis, laboratory data showed very similar findings. Diabetes, hypertension, and non-smoker status predicted glucose values >10 mmol/l on admission (p < 0.05) in a univariate analysis but only diabetes remained significant in a multivariate model (OR 23.3; 95% CI, 11.5-47.3). CONCLUSION: Diabetes predicts high glucose values on hospital admission for patients with ACS and patients are not being adequately controlled throughout CCU stay. PMID- 26903769 TI - Enhanced ex vivo intestinal absorption of olmesartan medoxomil nanosuspension: Preparation by combinative technology. AB - The purpose of this study was to develop nanosuspension based on combinative technology to enhance the intestinal absorption of Olmesartan medoxomil (OLM), a potent antihypertensive agent with limited oral bioavailability. Two combinative approaches were employed and then characterized. In vitro intestinal absorption of OLM nanosuspension and plain OLM was studied using non-everted rat intestinal sac model. Optimal OLM nanosuspension was prepared by a combination of ball milling and probe sonication using stabilizer, Poloxamer 407. The formula exhibited particle size of 469.9 nm and zeta potential of -19.1 mV, which was subjected to ex vivo studies. The flux and apparent permeability coefficient in intestine from OLM nanosuspension was higher than the plain drug, thereby suggesting better drug delivery. PMID- 26903768 TI - Formulation, preclinical and clinical evaluation of a new submicronic arginine respiratory fluid for treatment of chronic obstructive pulmonary disorder. AB - Inhalational drugs often suffer from low pulmonary deposition due to their micronized size. Aim of present study was development and evaluation of a novel submicronic L-arginine respiratory fluid formulation for treatment of cardiopulmonary complications associated with chronic obstructive pulmonary disorder (COPD). Objectives were (a) to develop and characterize submicronic L arginine respiratory fluid formulation, (b) pre-clinical safety/toxicity study in 2-animal species, (c) in vitro and in vivo evaluation in terms of respiratory fraction, and (d) clinical study to assess safety/efficacy in healthy volunteers/COPD patients. Formulation was optimized on the basis of particle size of aerosolized medication with particle size in the range of 400-500 nm. Anderson cascade impaction (ACI) studies were performed to validate the advantage in terms of respirable fraction, which indicated a high respirable fraction (51.61 +/- 3.28) for the developed formulation. In vivo pulmonary deposition pattern of optimized formulation was studied using gamma scintigraphy in human volunteers using (99m)Tc-arginine as radiotracer. It clearly demonstrated a significant pulmonary deposition of the submicronic formulation in various lung compartments. Efficacy of the developed formulation was further assessed in COPD patients (n = 15) by evaluating its effect on various cardiopulmonary parameters (spirometry, pulse-oxymetry, echocardiography and 6-min walk test). A marked improvement was seen in patients after inhalation of submicronic arginine in terms of their cardiopulmonary status. Results suggest that submicronic arginine respiratory fluid has the potential to be developed into an attractive therapeutic option for treating COPD associated cardiopulmonary complications. PMID- 26903770 TI - Formulation and evaluation of ileo-colonic targeted matrix-mini-tablets of Naproxen for chronotherapeutic treatment of rheumatoid arthritis. AB - In this present research work, the aim was to develop ileo-colonic targeted matrix-mini-tablets-filled capsule system of Naproxen for chronotherapeutic treatment of Rheumatoid Arthritis. So Matrix-mini-tablets of Naproxen were prepared using microsomal enzyme dependent and pH-sensitive polymers by direct compression method which were further filled into an empty HPMC capsule. The compatibility was assessed using FT-IR and DSC studies for pure drug, polymers and their physical mixtures. The prepared batches were subjected to physicochemical studies, drug content estimation, in-vitro drug release and stability studies. When FTIR and DSC studies were performed, it was found that there was no interaction between Naproxen and polymers used. The physicochemical properties of all the prepared matrix-mini-tablets batches were found to be in limits. The drug content percentage in the optimized formulation F18 was found to be 99.24 +/- 0.10%. Our optimized matrix-mini-tablets-filled-capsule formulation F18 releases Naproxen after a lag time of 2.45 +/- 0.97 h and 27.30 +/- 0.86%, 92.59 +/- 0.47%, 99.38 +/- 0.69% at the end of 5, 8, 12 h respectively. This formulation was also found to be stable as per the guidelines of International Conference on Harmonisation of Technical Requirements of Pharmaceuticals for Human Use. Thus, a novel ileo-colonic targeted delivery system of Naproxen was successfully developed by filling matrix-mini-tablets into an empty HPMC capsule shell for targeting early morning peak symptoms of rheumatoid arthritis. PMID- 26903771 TI - Pravastatin chitosan nanogels-loaded erythrocytes as a new delivery strategy for targeting liver cancer. AB - Chitosan nanogels (CNG) are developed as one of the most promising carriers for cancer targeting. However, these carriers are rapidly eliminated from circulation by reticuloendothelial system (RES), which limits their application. Therefore, erythrocytes (ER) loaded CNG as multifunctional carrier may overcome the massive elimination of nanocarriers by RES. In this study, erythrocytes loaded pravastatin-chitosan nanogels (PR-CNG-ER) were utilized as a novel drug carrier to target liver cancer. Thus, PR-CNG formula was developed in nanosize, with good entrapment efficiency, drug loading and sustained release over 48 h. Then, PR-CNG loaded into ER were prepared by hypotonic preswelling technique. The resulting PR CNG-ER showed 36.85% of entrapment efficiency, 66.82% of cell recovery and release consistent to that of hemoglobin over 48 h. Moreover, PR-CNG-ER exhibited negative zeta potential, increasing of hemolysis percent, marked phosphatidylserine exposure and stomatocytes shape compared to control unloaded erythrocytes. PR-CNG-ER reduced cells viability of HepG2 cells line by 28% compared to unloaded erythrocytes (UER). These results concluded that PR-CNG-ER are promising drug carriers to target liver cancer. PMID- 26903772 TI - Development and evaluation of natural gum-based extended release matrix tablets of two model drugs of different water solubilities by direct compression. AB - The study was aimed at developing extended release matrix tablets of poorly water soluble diclofenac sodium and highly water-soluble metformin hydrochloride by direct compression using cashew gum, xanthan gum and hydroxypropylmethylcellulose (HPMC) as release retardants. The suitability of light grade cashew gum as a direct compression excipient was studied using the SeDeM Diagram Expert System. Thirteen tablet formulations of diclofenac sodium (~100 mg) and metformin hydrochloride (~200 mg) were prepared with varying amounts of cashew gum, xanthan gum and HPMC by direct compression. The flow properties of blended powders and the uniformity of weight, crushing strength, friability, swelling index and drug content of compressed tablets were determined. In vitro drug release studies of the matrix tablets were conducted in phosphate buffer (diclofenac: pH 7.4; metformin: pH 6.8) and the kinetics of drug release was determined by fitting the release data to five kinetic models. Cashew gum was found to be suitable for direct compression, having a good compressibility index (ICG) value of 5.173. The diclofenac and metformin matrix tablets produced generally possessed fairly good physical properties. Tablet swelling and drug release in aqueous medium were dependent on the type and amount of release retarding polymer and the solubility of drug used. Extended release of diclofenac (~24 h) and metformin (~8-12 h) from the matrix tablets in aqueous medium was achieved using various blends of the polymers. Drug release from diclofenac tablets fitted zero order, first order or Higuchi model while release from metformin tablets followed Higuchi or Hixson Crowell model. The mechanism of release of the two drugs was mostly through Fickian diffusion and anomalous non-Fickian diffusion. The study has demonstrated the potential of blended hydrophilic polymers in the design and optimization of extended release matrix tablets for soluble and poorly soluble drugs by direct compression. PMID- 26903773 TI - An integrated Taguchi and response surface methodological approach for the optimization of an HPLC method to determine glimepiride in a supersaturatable self-nanoemulsifying formulation. AB - We studied the application of Taguchi orthogonal array (TOA) design during the development of an isocratic stability indicating HPLC method for glimepiride as per TOA design; twenty-seven experiments were conducted by varying six chromatographic factors. Percentage of organic phase was the most significant (p < 0.001) on retention time, while buffer pH had the most significant (p < 0.001) effect on tailing factor and theoretical plates. TOA design has shortcoming, which identifies the only linear effect, while ignoring the quadratic and interaction effects. Hence, a response surface model for each response was created including the linear, quadratic and interaction terms. The developed models for each response found to be well predictive bearing an acceptable adjusted correlation coefficient (0.9152 for retention time, 0.8985 for tailing factor and 0.8679 for theoretical plates). The models were found to be significant (p < 0.001) having a high F value for each response (15.76 for retention time, 13.12 for tailing factor and 9.99 for theoretical plates). The optimal chromatographic condition uses acetonitrile - potassium dihydrogen phosphate (pH 4.0; 30 mM) (50:50, v/v) as the mobile phase. The temperature, flow rate and injection volume were selected as 35 +/- 2 degrees C, 1.0 mL min(-1) and 20 MUL respectively. The method was validated as per ICH guidelines and was found to be specific for analyzing glimepiride from a novel supersaturatable self nanoemulsifying formulation. PMID- 26903774 TI - Synthesis, molecular properties, toxicity and biological evaluation of some new substituted imidazolidine derivatives in search of potent anti-inflammatory agents. AB - The aim of this study was to design and synthesize pharmaceutical agents containing imidazolidine heterocyclic ring in the hope of developing potent, safe and orally active anti-inflammatory agents. A number of substituted-imidazolidine derivatives (3a-k) were synthesized starting from ethylene diamine and aromatic aldehydes. The imidazolidine derivatives (3a-k) were investigated for their anticipated anti-inflammatory, and analgesic activity in Wistar albino rats and Swiss albino mice, respectively. Bioactivity score, molecular and pharmacokinetic properties of the imidazolidine derivatives were calculated by online computer software programs viz. Molinspiration and Osiris property explorer. The results of biological testing indicated that among the synthesized compounds only three imidazolidine derivatives namely 4-[1,3-Bis(2,6-dichlorobenzyl)-2 imidazolidinyl]phenyl-diethylamine (3g), 4-[1,3-Bis(3-hydroxy-4-methoxybenzyl)-2 imidazolidinyl]phenyl-diethylamine (3i) and 4-(1,3-Bis(4-methoxybenzyl)-4 methylimidazolidin-2-yl)-phenyl-diethylamine (3j) possess promising anti inflammatory and analgesic actions. Additionally these derivatives displayed superior GI safety profile (low severity index) with respect to the positive control, Indomethacin. All synthesized compounds showed promising bioactivity score for drug targets by Molinspiration software. Almost all the compounds were predicted to have very low toxicity risk by Osiris online software. Compound number (3i) emerged as a potential candidate for further research as it obeyed Lipinski's rule of five for drug likeness, exhibited promising biological activity in-vivo and showed no risk of toxicity in computer aided screening. PMID- 26903775 TI - Pharmacovigilance on sexual enhancing herbal supplements. AB - The use of herbal medicines continues to expand rapidly across world and many people show positive interest to use herbal products for their health. The safety of herbal supplements has become a globally major concern in national and international health authorities due to increasing adverse events and adulterations. It is difficult to analyze herbal products that cause adverse events due to lack of sufficient information and expertise. Inadequate regulatory measures, weak quality control system and uncontrolled distribution channels are some of reasons that enhance the informal pharmaceutical market. In recent years, the unfulfilled desire for sex has been a subject that has aroused increasing public interest with respect to improve sexual functions. The use of herbal medicines substantially increased due to escalated prevalence and impact of sexual problems worldwide and estimates predicting the incidence to raise over 320 million by year 2025. The various reasons to use herbal supplements in men may be due to experiencing changes in erectile dysfunction (ED) due to certain medical conditions such as diabetes and hypertension and bodily changes as a normal part of life and aging. There is a lack of adequate evidence, no impetus to evaluate and absence of any regulatory obligations to undertake rigorous testing for safety and efficacy of herbal supplements before they sold over-the counter (OTC). Pharmacovigilance on herbal supplements is still not well established. Sexual enhancing herbals are on demand in men health but informal adulteration is growing issue of concern. Recently, increase in use of herbal supplements for erectile dysfunction has laid a path for many illegal compositions. This paper explores facts and evidences that were observed in different countries attempting to demonstrate the importance of strengthening regulatory system to strengthen the application of pharmacovigilance principles on sexual enhancing supplements. We hereby explore the problem of sexual herbal supplements from pharmacovigilance perspectives. We provide insights into the various concerns and call for collaboration to resolve the problem. We highly recommend to include herbal medicines in national pharmacovigilance systems and to establish comprehensive national pharmacovigilance program to raise the awareness about herbal medicines particularly those used in enhancing sexual desire. PMID- 26903776 TI - Energy Use Consequences of Ventilating a Net-Zero Energy House. AB - A Net-Zero Energy Residential Test Facility (NZERTF) has been constructed at the National Institute of Standards and Technology (NIST) in Gaithersburg, Maryland to demonstrate that a home similar in size, aesthetics, and amenities to those in the surrounding communities can achieve net-zero energy use over the course of a year while meeting the average electricity and water use needs of a family of four in the United States. The facility incorporates renewable energy and energy efficient technologies, including an air-to-air heat pump system, a solar photovoltaic system, a solar thermal domestic hot water system, and a heat recovery ventilation system sized to meet American Society of Heating, Refrigeration, and Air-Conditioning Engineers (ASHRAE) Standard 62.2-2010 ventilation requirements. The largest energy end use within the home was space conditioning, which included heat loss through the building envelope, ventilation air supplied by the heat recovery ventilator (HRV), and internal loads. While HRVs are often described as being able to save energy when compared to ventilating without heat recovery, there have been no studies using a full year of measured data that determine the thermal load and energy impacts of HRV-based ventilation on the central heating and cooling system. Over the course of a year, continuous operation of the HRV at the NZERTF resulted in an annual savings of 7 % in heat pump energy use compared with the hypothetical case of ventilating without heat recovery. The heat pump electrical use varied from an increase of 5 % in the cooling months to 36 % savings in the heating months compared with ventilation without heat recovery. The increase in the cooling months occurred when the outdoor temperature was lower than the indoor temperature, during which the availability of an economizer mode would have been beneficial. Nevertheless, the fan energy required to operate the selected HRV at the NZERTF paid for itself in the heat pump energy saved compared with ventilation without heat recovery. PMID- 26903777 TI - Biosimilars: Extrapolating the evidence. A roundtable discussion. PMID- 26903778 TI - Feshbach enhanced s-wave scattering of fermions: direct observation with optimized absorption imaging. AB - We directly measured the normalized s-wave scattering cross-section of ultracold 40K atoms across a magnetic-field Feshbach resonance by colliding pairs of degenerate Fermi gases (DFGs) and imaging the scattered atoms. We extracted the scattered fraction for a range of bias magnetic fields, and measured the resonance location to be B0 = 20.206(15) mT with width Delta = 1.0(5) mT. To optimize the signal-to-noise ratio of atom number in scattering images, we developed techniques to interpret absorption images in a regime where recoil induced detuning corrections are significant. These imaging techniques are generally applicable to experiments with lighter alkalis that would benefit from maximizing signal-to-noise ratio on atom number counting at the expense of spatial imaging resolution. PMID- 26903779 TI - Erratum to: ENOX2-based early detection (ONCOblot) of asbestos-induced malignant mesothelioma 4-10 years in advance of clinical symptoms. AB - [This corrects the article DOI: 10.1186/s12014-016-9103-3.]. PMID- 26903780 TI - Assessment of Pharmacy Information System Performance in Three Hospitals in Eastern Province, Saudi Arabia. AB - The pharmacy information system is one of the central pillars of a hospital information system. This research evaluated a pharmacy information system according to six aspects of the medication process in three hospitals in Eastern Province, Saudi Arabia. System administrators were interviewed to determine availability of functionalities. Then, system users within the hospital were targeted to evaluate their level of usage of these functionalities. The study was cross-sectional. Two structured surveys were designed. The overall response rate of hospital users was 31.7 percent. In all three hospitals studied, the electronic health record is hybrid, implementation has been completed and the system is running, and the systems have computerized provider order entry and clinical decision support. Also, the pharmacy information systems are integrated with the electronic health record, and computerized provider order entry and almost all prescribing and transcription functionalities are available; however, drug dispensing is a mostly manual process. However, the study hospitals do not use barcode-assisted medication administration systems to verify patient identity and electronically check dose administration, and none of them have computerized adverse drug event monitoring that uses the electronic health record. The numbers of users who used different functionalities most or all of the time was generally low. The highest frequency of utilization was for patient administration records (56.8 percent), and the lowest was for linkage of the pharmacy information system to pharmacy stock (9.1 percent). Encouraging users to use different functionalities was highly recommended. PMID- 26903781 TI - Digital Family History Data Mining with Neural Networks: A Pilot Study. AB - Following the passage of the Health Information Technology for Economic and Clinical Health (HITECH) Act of 2009, electronic health records were widely adopted by eligible physicians and hospitals in the United States. Stage 2 meaningful use menu objectives include a digital family history but no stipulation as to how that information should be used. A variety of data mining techniques now exist for these data, which include artificial neural networks (ANNs) for supervised or unsupervised machine learning. In this pilot study, we applied an ANN-based simulation to a previously reported digital family history to mine the database for trends. A graphical user interface was created to display the input of multiple conditions in the parents and output as the likelihood of diabetes, hypertension, and coronary artery disease in male and female offspring. The results of this pilot study show promise in using ANNs to data mine digital family histories for clinical and research purposes. PMID- 26903782 TI - Electronic Health Record Use a Bitter Pill for Many Physicians. AB - Electronic health record (EHR) adoption among office-based physician practices in the United States has increased significantly in the past decade. However, the challenges of using EHRs have resulted in growing dissatisfaction with the systems among many of these physicians. The purpose of this qualitative multiple case study was to increase understanding of physician perceptions regarding the value of using EHR technology. Important findings included the belief among physicians that EHR systems need to be more user-friendly and adaptable to individual clinic workflow preferences, physician beliefs that lack of interoperability among EHRs is a major barrier to meaningful use of the systems, and physician beliefs that EHR use does not improve the quality of care provided to patients. These findings suggest that although government initiatives to encourage EHR adoption among office-based physician practices have produced positive results, additional support may be required in the future to maintain this momentum. PMID- 26903783 TI - Predicting 30- to 120-Day Readmission Risk among Medicare Fee-for-Service Patients Using Nonmedical Workers and Mobile Technology. AB - OBJECTIVE: Hospital readmissions are a large source of wasteful healthcare spending, and current care transition models are too expensive to be sustainable. One way to circumvent cost-prohibitive care transition programs is complement nurse-staffed care transition programs with those staffed by less expensive nonmedical workers. A major barrier to utilizing nonmedical workers is determining the appropriate time to escalate care to a clinician with a wider scope of practice. The objective of this study is to show how mobile technology can use the observations of nonmedical workers to stratify patients on the basis of their hospital readmission risk. MATERIALS AND METHODS: An area agency on aging in Massachusetts implemented a quality improvement project with the aim of reducing 30-day hospital readmission rates using a modified care transition intervention supported by mobile predictive analytics technology. Proprietary readmission risk prediction algorithms were used to predict 30-, 60-, 90-, and 120-day readmission risk. RESULTS: The risk score derived from the nonmedical workers' observations had a significant association with 30-day readmission rate with an odds ratio (OR) of 1.12 (95 percent confidence interval [CI], 1 .09-1.15) compared to an OR of 1.25 (95 percent CI, 1.19-1.32) for the risk score using nurse observations. Risk scores using nurse interpretation of nonmedical workers' observations show that patients in the high-risk category had significantly higher readmission rates than patients in the baseline-risk and mild-risk categories at 30, 60, 90, and 120 days after discharge. Of the 1,064 elevated risk alerts that were triaged, 1,049 (98.6 percent) involved the nurse care manager, 804 (75.6 percent) involved the patient, 768 (72.2 percent) involved the health coach, 461 (43.3 percent) involved skilled nursing, and 235 (22.1 percent) involved the outpatient physician in the coordination of care in response to the alert. DISCUSSION: The predictive nature of the 30-day readmission risk scores is influenced by both nurse and nonmedical worker input, and both are required to adequately triage the needs of the patient. CONCLUSION: Although this preliminary study is limited by a modest effect size, it demonstrates one approach to using technology to contribute to delivery model innovation that could curb wasteful healthcare spending by tapping into an existing underutilized workforce. PMID- 26903784 TI - Surgical Precision in Clinical Documentation Connects Patient Safety, Quality of Care, and Reimbursement. AB - Emphasis on quality of care has become a major focus for healthcare providers and institutions. The Centers for Medicare and Medicaid Services has multiple quality of-care performance programs and initiatives aimed at providing transparency to the public, which provide the ability to directly compare services provided by hospitals and individual physicians. These quality-of-care programs highlight the transition to pay for performance, rewarding physicians and hospitals for high quality of care. To improve the use of pay for performance and analyze quality-of care outcome measures, the Division of Plastic Surgery at Scott & White Memorial Hospital participated in an inpatient clinical documentation accuracy project (CDAP). Performance and improvement on metrics such as case mix index, severity of illness, risk of mortality, and geometric mean length of stay were assessed after implementation. After implementation of the CDAP, the division of plastic surgery showed increases in case mix index, calculated severity of illness, and calculated risk of mortality and a decrease in length of stay. For academic plastic surgeons, quality of care demands precise documentation of each patient. The CDAP provides one avenue to hone clinical documentation and performance on quality measures. PMID- 26903785 TI - Nanosilver Biocidal Properties and Their Application in Disinfection of Hatchers in Poultry Processing Plants. AB - The aim of this study was to use aqueous suspensions of silver nanoparticles with a wide spectrum of particle sizes, variable morphology, high stability, and appropriate physicochemical properties to examine their bactericidal and fungicidal properties against microorganisms present in poultry processing plants. At the same time, the particles were tested for preventing the production of odorogenous pollutants during incubation and thereby reducing the emission of harmful gases from such types of facilities. The results show that the use of nanosilver preparations in order to disinfect eggs and hatchers reduced microbiological contamination. The bactericidal and fungicidal efficacy of the applied preparation was comparable to UV radiation and its effectiveness increasing during the incubation. Good results were achieved in terms of the level of organic gaseous contaminants, which decreased by 86% after the application of the nanosilver preparation. PMID- 26903786 TI - Mechanical and Biological Interactions of Implants with the Brain and Their Impact on Implant Design. AB - Neural prostheses have already a long history and yet the cochlear implant remains the only success story about a longterm sensory function restoration. On the other hand, neural implants for deep brain stimulation are gaining acceptance for variety of disorders including Parkinsons disease and obsessive-compulsive disorder. It is anticipated that the progress in the field has been hampered by a combination of technological and biological factors, such as the limited understanding of the longterm behavior of implants, unreliability of devices, biocompatibility of the implants among others. While the field's understanding of the cell biology of interactions at the biotic-abiotic interface has improved, relatively little attention has been paid on the mechanical factors (stress, strain), and hence on the geometry that can modulate it. This focused review summarizes the recent progress in the understanding of the mechanisms of mechanical interaction between the implants and the brain. The review gives an overview of the factors by which the implants interact acutely and chronically with the tissue: blood-brain barrier (BBB) breach, vascular damage, micromotions, diffusion etc. We propose some design constraints to be considered in future studies. Aspects of the chronic cell-implant interaction will be discussed in view of the chronic local inflammation and the ways of modulating it. PMID- 26903788 TI - Potential Mechanisms Supporting the Value of Motor Cortex Stimulation to Treat Chronic Pain Syndromes. AB - Throughout the first years of the twenty-first century, neurotechnologies such as motor cortex stimulation (MCS), transcranial magnetic stimulation (TMS), and transcranial direct current stimulation (tDCS) have attracted scientific attention and been considered as potential tools to centrally modulate chronic pain, especially for those conditions more difficult to manage and refractory to all types of available pharmacological therapies. Interestingly, although the role of the motor cortex in pain has not been fully clarified, it is one of the cortical areas most commonly targeted by invasive and non-invasive neuromodulation technologies. Recent studies have provided significant advances concerning the establishment of the clinical effectiveness of primary MCS to treat different chronic pain syndromes. Concurrently, the neuromechanisms related to each method of primary motor cortex (M1) modulation have been unveiled. In this respect, the most consistent scientific evidence originates from MCS studies, which indicate the activation of top-down controls driven by M1 stimulation. This concept has also been applied to explain M1-TMS mechanisms. Nevertheless, activation of remote areas in the brain, including cortical and subcortical structures, has been reported with both invasive and non-invasive methods and the participation of major neurotransmitters (e.g., glutamate, GABA, and serotonin) as well as the release of endogenous opioids has been demonstrated. In this critical review, the putative mechanisms underlying the use of MCS to provide relief from chronic migraine and other types of chronic pain are discussed. Emphasis is placed on the most recent scientific evidence obtained from chronic pain research studies involving MCS and non-invasive neuromodulation methods (e.g., tDCS and TMS), which are analyzed comparatively. PMID- 26903789 TI - Autism Spectrum Disorders and Drug Addiction: Common Pathways, Common Molecules, Distinct Disorders? AB - Autism spectrum disorders (ASDs) and drug addiction do not share substantial comorbidity or obvious similarities in etiology or symptomatology. It is thus surprising that a number of recent studies implicate overlapping neural circuits and molecular signaling pathways in both disorders. The purpose of this review is to highlight this emerging intersection and consider implications for understanding the pathophysiology of these seemingly distinct disorders. One area of overlap involves neural circuits and neuromodulatory systems in the striatum and basal ganglia, which play an established role in addiction and reward but are increasingly implicated in clinical and preclinical studies of ASDs. A second area of overlap relates to molecules like Fragile X mental retardation protein (FMRP) and methyl CpG-binding protein-2 (MECP2), which are best known for their contribution to the pathogenesis of syndromic ASDs, but have recently been shown to regulate behavioral and neurobiological responses to addictive drug exposure. These shared pathways and molecules point to common dimensions of behavioral dysfunction, including the repetition of behavioral patterns and aberrant reward processing. The synthesis of knowledge gained through parallel investigations of ASDs and addiction may inspire the design of new therapeutic interventions to correct common elements of striatal dysfunction. PMID- 26903792 TI - Subject-Controlled, On-demand, Dorsal Genital Nerve Stimulation to Treat Urgency Urinary Incontinence; a Pilot. AB - OBJECTIVES: To evaluate the effect of subject-controlled, on-demand, dorsal genital nerve (DGN) stimulation on non-neurogenic urgency urinary incontinence (UUI) in a domestic setting. MATERIALS AND METHODS: Non-neurogenic patients >18 years with overactive bladder symptoms and UUI were included. Exclusion criteria were mainly stress urinary incontinence. Patients underwent 1 week of subject controlled, on-demand, DGN stimulation, delivered by a percutaneously placed electrode near the DGN connected to an external stimulator (pulse-rate 20 Hz, pulse-width 300 MUs). Patients activated the stimulator when feeling the urge to void and stimulated for 30 s. The amplitude was set at the highest tolerable level. A bladder diary including a severity score of the UUI episodes/void (scores: 0 = none, 1 = drops, 2 = dashes, 3 = soaks) and a padtest was kept 3 days prior to, during, and 3 days after the test period. The subjective improvement was also scored. RESULTS: Seven patients (4 males/3 females) were enrolled, the mean age was 55 years (range 23-73). Six completed the test week. In the remaining patient the electrode migrated and was removed. 5/6 finalized the complete bladder diary, 1/6 recorded only the heavy incontinence episodes (score = 3). 4/6 completed the padtest. In all patients who finalized the bladder diary the number of UUI episodes decreased, in 3/5 with >=60%. The heavy incontinence episodes (score = 3) were resolved in 2/6 patients, and improved >=80% in the other 4. The severity score of the UUI episodes/void was improved with >= 60% in 3/5 patients. The mean subjective improvement was 73%. CONCLUSION: This feasibility study indicates that subject-controlled, on-demand DGN stimulation using a percutaneously placed electrode is possible over a longer time period, in a home setting, with a positive effect on non-neurogenic overactive bladder symptoms with UUI. Although the placement is an easy procedure, it is difficult to fixate the electrode to keep it in the correct position. Improvements in hardware, like a better fixated electrode and an easy to control stimulator, are necessary to make SODGNS a treatment possibility in the future. PMID- 26903790 TI - Glucocorticoid Regulation of Food-Choice Behavior in Humans: Evidence from Cushing's Syndrome. AB - The mechanisms by which glucocorticoids regulate food intake and resulting body mass in humans are not well-understood. One potential mechanism could involve modulation of reward processing, but human stress models examining effects of glucocorticoids on behavior contain important confounds. Here, we studied individuals with Cushing's syndrome, a rare endocrine disorder characterized by chronic excess endogenous glucocorticoids. Twenty-three patients with Cushing's syndrome (13 with active disease; 10 with disease in remission) and 15 controls with a comparably high body mass index (BMI) completed two simulated food-choice tasks (one with "explicit" task contingencies and one with "probabilistic" task contingencies), during which they indicated their objective preference for viewing high calorie food images vs. standardized pleasant, unpleasant, and neutral images. All participants also completed measures of food craving, and approximately half of the participants provided 24-h urine samples for assessment of cortisol and cortisone concentrations. Results showed that on the explicit task (but not the probabilistic task), participants with active Cushing's syndrome made fewer food-related choices than participants with Cushing's syndrome in remission, who in turn made fewer food-related choices than overweight controls. Corroborating this group effect, higher urine cortisone was negatively correlated with food-related choice in the subsample of all participants for whom these data were available. On the probabilistic task, despite a lack of group differences, higher food-related choice correlated with higher state and trait food craving in active Cushing's patients. Taken together, relative to overweight controls, Cushing's patients, particularly those with active disease, displayed a reduced vigor of responding for food rewards that was presumably attributable to glucocorticoid abnormalities. Beyond Cushing's, these results may have relevance for elucidating glucocorticoid contributions to food seeking behavior, enhancing mechanistic understanding of weight fluctuations associated with oral glucocorticoid therapy and/or chronic stress, and informing the neurobiology of neuropsychiatric conditions marked by abnormal cortisol dynamics (e.g., major depression, Alzheimer's disease). PMID- 26903791 TI - To Hear or Not to Hear: Sound Availability Modulates Sensory-Motor Integration. AB - When we walk in place with our eyes closed after a few minutes of walking on a treadmill, we experience an unintentional forward body displacement (drift), called the sensory-motor aftereffect. Initially, this effect was thought to be due to the mismatch experienced during treadmill walking between the visual (absence of optic flow signaling body steadiness) and proprioceptive (muscle spindles firing signaling body displacement) information. Recently, the persistence of this effect has been shown even in the absence of vision, suggesting that other information, such as the sound of steps, could play a role. To test this hypothesis, six cochlear-implanted individuals were recruited and their forward drift was measured before (Control phase) and after (Post Exercise phase) walking on a treadmill while having their cochlear system turned on and turned off. The relevance in testing cochlear-implanted individuals was that when their system is turned off, they perceive total silence, even eliminating the sounds normally obtained from bone conduction. Results showed the absence of the aftereffect when the system was turned off, underlining the fundamental role played by sounds in the control of action and breaking new ground in the use of interactive sound feedback in motor learning and motor development. PMID- 26903787 TI - Fischer 344 and Lewis Rat Strains as a Model of Genetic Vulnerability to Drug Addiction. AB - Today it is well acknowledged that both nature and nurture play important roles in the genesis of psychopathologies, including drug addiction. Increasing evidence suggests that genetic factors contribute for at least 40-60% of the variation in liability to drug dependence. Human genetic studies suggest that multiple genes of small effect, rather than single genes, contribute to the genesis of behavioral psychopathologies. Therefore, the use of inbred rat strains might provide a valuable tool to identify differences, linked to genotype, important in liability to addiction and related disorders. In this regard, Lewis and Fischer 344 inbred rats have been proposed as a model of genetic vulnerability to drug addiction, given their innate differences in sensitivity to the reinforcing and rewarding effects of drugs of abuse, as well their different responsiveness to stressful stimuli. This review will provide evidence in support of this model for the study of the genetic influence on addiction vulnerability, with particular emphasis on differences in mesolimbic dopamine (DA) transmission, rewarding and emotional function. It will be highlighted that Lewis and Fischer 344 rats differ not only in several indices of DA transmission and adaptive changes following repeated drug exposure, but also in hypothalamic-pituitary adrenal (HPA) axis responsiveness, influencing not only the ability of the individual to cope with stressful events, but also interfering with rewarding and motivational processes, given the influence of corticosteroids on dopamine neuron functionality. Further differences between the two strains, as impulsivity or anxiousness, might contribute to their different proneness to addiction, and likely these features might be linked to their different DA neurotransmission plasticity. Although differences in other neurotransmitter systems might deserve further investigation, results from the reviewed studies might open new vistas in understanding aberrant deviations in reward and motivational functions. PMID- 26903793 TI - Assessment of the Neuroprotective Effects of Lavandula angustifolia Extract on the Contusive Model of Spinal Cord Injury in Wistar Rats. AB - INTRODUCTION: Spinal cord injury (SCI) involves a primary trauma and secondary cellular processes that can lead to severe damage to the nervous system, resulting in long-term spinal deficits. At the cellular level, SCI causes astrogliosis, of which glial fibrillary acidic protein (GFAP) is a major index. OBJECTIVE: The aim of this study was to investigate the neuroprotective effects of Lavandula angustifolia (Lav) on the repair of spinal cord injuries in Wistar rats. MATERIALS AND METHODS: Forty-five female rats were randomly divided into six groups of seven rats each: the intact, sham, control (SCI), Lav 100, Lav 200, and Lav 400 groups. Every week after SCI onset, all animals were evaluated for behavior outcomes by the Basso, Beattie, and Bresnahan (BBB) score. H&E staining was performed to examine the lesions post-injury. GFAP expression was assessed for astrogliosis. Somatosensory evoked potential (SEP) testing was performed to detect the recovery of neural conduction. RESULTS: BBB scores were significantly increased and delayed responses on sensory tests were significantly decreased in the Lav 200 and Lav 400 groups compared to the control group. The greatest decrease of GFAP was evident in the Lav 200 and Lav 400 groups. EMG results showed significant improvement in the hindlimbs in the Lav 200 and Lav 400 groups compared to the control group. Cavity areas significantly decreased and the number of ventral motor neurons significantly increased in the Lav 200 and Lav 400 groups. CONCLUSION: Lav at doses of 200 and 400 mg/kg can promote structural and functional recovery after SCI. The neuroprotective effects of L. angustifolia can lead to improvement in the contusive model of SCI in Wistar rats. PMID- 26903797 TI - Editorial: Scents that Matter-from Olfactory Stimuli to Genes, Behaviors and Beyond. PMID- 26903794 TI - Regulation of Neurogenesis by Neurotrophins during Adulthood: Expected and Unexpected Roles. AB - The subventricular zone (SVZ) of the anterolateral ventricle and the subgranular zone (SGZ) of the hippocampal dentate gyrus are the two main regions of the adult mammalian brain in which neurogenesis is maintained throughout life. Because alterations in adult neurogenesis appear to be a common hallmark of different neurodegenerative diseases, understanding the molecular mechanisms controlling adult neurogenesis is a focus of active research. Neurotrophic factors are a family of molecules that play critical roles in the survival and differentiation of neurons during development and in the control of neural plasticity in the adult. Several neurotrophins and neurotrophin receptors have been implicated in the regulation of adult neurogenesis at different levels. Here, we review the current understanding of neurotrophin modulation of adult neurogenesis in both the SVZ and SGZ. We compile data supporting a variety of roles for neurotrophins/neurotrophin receptors in different scenarios, including both expected and unexpected functions. PMID- 26903796 TI - Restoring Behavior via Inverse Neurocontroller in a Lesioned Cortical Spiking Model Driving a Virtual Arm. AB - Neural stimulation can be used as a tool to elicit natural sensations or behaviors by modulating neural activity. This can be potentially used to mitigate the damage of brain lesions or neural disorders. However, in order to obtain the optimal stimulation sequences, it is necessary to develop neural control methods, for example by constructing an inverse model of the target system. For real brains, this can be very challenging, and often unfeasible, as it requires repeatedly stimulating the neural system to obtain enough probing data, and depends on an unwarranted assumption of stationarity. By contrast, detailed brain simulations may provide an alternative testbed for understanding the interactions between ongoing neural activity and external stimulation. Unlike real brains, the artificial system can be probed extensively and precisely, and detailed output information is readily available. Here we employed a spiking network model of sensorimotor cortex trained to drive a realistic virtual musculoskeletal arm to reach a target. The network was then perturbed, in order to simulate a lesion, by either silencing neurons or removing synaptic connections. All lesions led to significant behvaioral impairments during the reaching task. The remaining cells were then systematically probed with a set of single and multiple-cell stimulations, and results were used to build an inverse model of the neural system. The inverse model was constructed using a kernel adaptive filtering method, and was used to predict the neural stimulation pattern required to recover the pre-lesion neural activity. Applying the derived neurostimulation to the lesioned network improved the reaching behavior performance. This work proposes a novel neurocontrol method, and provides theoretical groundwork on the use biomimetic brain models to develop and evaluate neurocontrollers that restore the function of damaged brain regions and the corresponding motor behaviors. PMID- 26903795 TI - Striatal Circuits as a Common Node for Autism Pathophysiology. AB - Autism spectrum disorders (ASD) are characterized by two seemingly unrelated symptom domains-deficits in social interactions and restrictive, repetitive patterns of behavioral output. Whether the diverse nature of ASD symptomatology represents distributed dysfunction of brain networks or abnormalities within specific neural circuits is unclear. Striatal dysfunction is postulated to underlie the repetitive motor behaviors seen in ASD, and neurological and brain imaging studies have supported this assumption. However, as our appreciation of striatal function expands to include regulation of behavioral flexibility, motivational state, goal-directed learning, and attention, we consider whether alterations in striatal physiology are a central node mediating a range of autism associated behaviors, including social and cognitive deficits that are hallmarks of the disease. This review investigates multiple genetic mouse models of ASD to explore whether abnormalities in striatal circuits constitute a common pathophysiological mechanism in the development of autism-related behaviors. Despite the heterogeneity of genetic insult investigated, numerous genetic ASD models display alterations in the structure and function of striatal circuits, as well as abnormal behaviors including repetitive grooming, stereotypic motor routines, deficits in social interaction and decision-making. Comparative analysis in rodents provides a unique opportunity to leverage growing genetic association data to reveal canonical neural circuits whose dysfunction directly contributes to discrete aspects of ASD symptomatology. The description of such circuits could provide both organizing principles for understanding the complex genetic etiology of ASD as well as novel treatment routes. Furthermore, this focus on striatal mechanisms of behavioral regulation may also prove useful for exploring the pathogenesis of other neuropsychiatric diseases, which display overlapping behavioral deficits with ASD. PMID- 26903798 TI - Tau: The Center of a Signaling Nexus in Alzheimer's Disease. AB - Tau is a microtubule-associated protein whose misfolding, hyper-phosphorylation, loss of normal function and toxic gain of function are linked to several neurodegenerative disorders, including Alzheimer's disease (AD). This review discusses the role of tau in amyloid-beta (Abeta) induced toxicity in AD. The consequences of tau dysfunction, starting from the axon and concluding at somadendritic compartments, will be highlighted. PMID- 26903800 TI - Alcohol, Excitotoxicity and Adult Brain Damage: An Experimentally Unproven Chain of-Events. PMID- 26903799 TI - ICU Blood Pressure Variability May Predict Nadir of Respiratory Depression After Coronary Artery Bypass Surgery. AB - OBJECTIVES: Surgical stress induces alterations on sympathovagal balance that can be determined through assessment of blood pressure variability. Coronary artery bypass graft surgery (CABG) is associated with postoperative respiratory depression. In this study we aimed at investigating ICU blood pressure variability and other perioperative parameters that could predict the nadir of postoperative respiratory function impairment. METHODS: This prospective observational study evaluated 44 coronary artery disease patients subjected to coronary artery bypass surgery (CABG) with cardiopulmonary bypass (CPB). At the ICU, mean arterial pressure (MAP) was monitored every 30 min for 3 days. MAP variability was evaluated through: standard deviation (SD), coefficient of variation (CV), variation independent of mean (VIM), and average successive variability (ASV). Respiratory function was assessed through maximal inspiratory (MIP) and expiratory (MEP) pressures and peak expiratory flow (PEF) determined 1 day before surgery and on the postoperative days 3rd to 7th. Intraoperative parameters (volume of cardioplegia, CPB duration, aortic cross-clamp time, number of grafts) were also monitored. RESULTS: Since, we aimed at studying patients without confounding effects of postoperative complications on respiratory function, we had enrolled a cohort of low risk EuroSCORE (European System for Cardiac Operative Risk Evaluation) with < 2. Respiratory parameters MIP, MEP, and PEF were significantly depressed for 4-5 days postoperatively. Of all MAP variability parameters, the ASV had a significant good positive Spearman correlation (rho coefficients ranging from 0.45 to 0.65, p < 0.01) with the 3-day nadir of PEF after cardiac surgery. Also, CV and VIM of MAP were significantly associated with nadir days of MEP and PEF. None of the intraoperative parameters had any correlation with the postoperative respiratory depression. CONCLUSIONS: Variability parameters ASV, CV, and VIM of the MAP monitored at ICU may have predictive value for the depression of respiratory function after cardiac surgery as determined by peak expiratory flow and maximal expiratory pressure. ClinicalTrials.gov Identifier: NCT02074371. PMID- 26903802 TI - SNARE Protein Syntaxin-1 Colocalizes Closely with NMDA Receptor Subunit NR2B in Postsynaptic Spines in the Hippocampus. AB - Syntaxins are a family of membrane-integrated proteins that are instrumental in exocytosis of vesicles. Syntaxin-1 is an essential component of the presynaptic exocytotic fusion machinery in the brain and interacts with several other proteins. Syntaxin-1 forms a four-helical bundle complex with proteins SNAP-25 and VAMP2 that drives fusion of vesicles with the plasma membrane in the active zone (AZ). Little is known, however, about the ultrastructural localization of syntaxin-1 at the synapse. We have analyzed the intrasynaptic expression of syntaxin-1 in glutamatergic hippocampal synapses in detail by using quantitative postembedding immunogold labeling. Syntaxin-1 was present in highest concentrations at the presynaptic AZ, supporting its role in transmitter release. Presynaptic plasma membrane lateral to the AZ, as well as presynaptic cytoplasmic (PreCy) vesicles were also labeled. However, syntaxin-1 was also significantly expressed in postsynaptic spines, where it was localized at the postsynaptic density (PSD), at postsynaptic lateral membranes and in postsynaptic cytoplasm. Postsynaptically, syntaxin-1 colocalized in the nanometer range with the N-methyl D-aspartate (NMDA) receptor subunit NR2B, but only weakly with the AMPA receptor subunits GluA2/3. This observation points to the possibility that syntaxin-1 may be involved with NR2B vesicular trafficking from cytoplasmic stores to the postsynaptic plasma membrane, thus facilitating synaptic plasticity. Confocal immunofluorescence double labeling with PSD-95 and ultrastructural fractionation of synaptosomes also confirm localization of syntaxin-1 at the PSD. PMID- 26903801 TI - MiRNA-200b Regulates RMP7-Induced Increases in Blood-Tumor Barrier Permeability by Targeting RhoA and ROCKII. AB - The primary goals of this study were to investigate the potential roles of miR 200b in regulating RMP7-induced increases in blood-tumor barrier (BTB) permeability and some of the possible molecular mechanisms associated with this effect. Microarray analysis revealed 34 significantly deregulated miRNAs including miR-200b in the BTB as induced by RMP7 and 8 significantly up-regulated miRNAs in the BTB by RMP7. RMP7 induced tight junction (TJ) opening of the BTB, thereby increasing BTB permeability. Associated with this effect of RMP7 was a decrease in miR-200b expression within the human cerebral microvascular endothelial cells line hCMEC/D3 (ECs) of the BTB. Overexpression of miR-200b inhibited endothelial leakage and restored normal transendothelial electric resistance values. A simultaneous shift in occludin and claudin-5 distributions from insoluble to soluble fractions were observed to be significantly reduced. In addition, overexpression of miR-200b inhibited the relocation of occludin and claudin-5 from cellular borders into the cytoplasm as well as the production of stress fiber formation in GECs (ECs with U87 glioma cells co-culturing) of the BTB. MiR-200b silencing produced opposite results as that obtained from that of the miR-200b overexpression group. Overexpression of miR-200b was also associated with a down-regulation in RhoA and ROCKII expression, concomitant with a decrease in BTB permeability. Again, results which were opposite to that obtained with the miR-200b silencing group. We further found that miR-200b regulated BTB permeability by directly targeting RhoA and ROCKII. Collectively, these results suggest that miR-200b's contribution to the RMP7-induced increase in BTB permeability was associated with stress fiber formation and TJ disassembly as achieved by directly targeting RhoA and ROCKII. PMID- 26903803 TI - Characterization of a Novel Chromatin Sorting Tool Reveals Importance of Histone Variant H3.3 in Contextual Fear Memory and Motor Learning. AB - The consolidation of short-term labile memories for long-term storage requires transcription and there is growing interest in defining the epigenetic mechanisms regulating these transcriptional events. In particular, it has been hypothesized that combinations of histone post-translational modifications (PTMs) have the potential to store memory by dynamically defining the transcriptional status of any given gene loci. Studying epigenetic phenomena during long-term memory consolidation, however, is complicated by the complex cellular heterogeneity of the brain, in which epigenetic signal from memory-relevant cells can be obscured or diluted by the surrounding milieu. To address this issue, we have developed a transgenic mouse line expressing a tetO-regulated, hemagglutinin (HA)-tagged histone H3.3 exclusively in excitatory neurons of the forebrain. Unlike canonical histones, histone H3.3 is incorporated at promoter regions of transcriptionally active genes in a DNA replication-independent manner, stably "barcoding" active regions of the genome in post-mitotic cells. Immunoprecipitating H3.3-HA containing nucleosomes from the hippocampus will therefore enrich for memory relevant chromatin by isolating actively transcribed regions of the excitatory neuron genome. To evaluate the validity of using H3.3 "barcoding" to sort chromatin, we performed a molecular and behavioral characterization of the H3.3 HA transgenic mouse line. Expectedly, we find that H3.3-HA is incorporated preferentially at promoter regions of actively-transcribed neuronal genes and that expression can be effectively regulated by doxycycline. Additionally, H3.3 HA overexpression does not adversely affect exploratory or anxiety-related behaviors, nor does it affect spatial memory. Transgenic animals do, however, exhibit deficits in contextual memory and motor learning, revealing the importance of this histone isoform in the brain. Future studies in the H3.3-HA transgenic mouse line will define the combinatorial histone PTM landscape during spatial memory consolidation and will investigate the important contributions of histone H3.3 to the normal functioning of the brain. PMID- 26903804 TI - Striatal Plasticity in L-DOPA- and Graft-Induced Dyskinesia; The Common Link? AB - One of the major symptoms of the neurodegenerative condition Parkinson's disease (PD) is a slowness or loss of voluntary movement, yet frustratingly therapeutic strategies designed to restore movement can result in the development of excessive abnormal movements known as dyskinesia. These dyskinesias commonly develop as a result of pharmacotherapy in the form of L-DOPA administration, but have also been identified following deep brain stimulation (DBS) and intrastriatal cell transplantation. In the case of L-DOPA these movements can be treatment limiting, and whilst they are not long lasting or troubling following DBS, recognition of their development had a near devastating effect on the field of cell transplantation for PD.Understanding the relationship between these therapeutic approaches and the development of dyskinesia may improve our ability to restore function without disabling side effects. Interestingly, despite the fact that dopaminergic cell transplantation repairs many of the changes induced by the disease process and through L-DOPA treatment, there appears to be a relationship between the two. In rodent models of the disease, the severity of dyskinesia induced by L-DOPA prior to the transplantation procedure correlated with post-transplantation, graft-induced dyskinesia. A review of clinical data also suggested that the worse preoperational dyskinesia causes worsened graft induced dyskinesia (GID). Understanding how these aberrant behaviors come about has been of keen interest to open up these therapeutic options more widely and one major underlying theory is the effects of these approaches on the plasticity of synapses within the basal ganglia. This review uniquely brings together developments in understanding the role of striatal synaptic plasticity in both L DOPA and GID to guide and stimulate further investigations on the important striatal plasticity. PMID- 26903805 TI - JNK Inhibition Inhibits Lateral Line Neuromast Hair Cell Development. AB - JNK signaling is known to play a role in regulating cell behaviors such as cell cycle progression, cell proliferation, and apoptosis, and recent studies have suggested important roles for JNK signaling in embryonic development. However, the precise function of JNK signaling in hair cell development remains poorly studied. In this study, we used the small molecule JNK inhibitor SP600125 to examine the effect of JNK signaling abrogation on the development of hair cells in the zebrafish lateral line neuromast. Our results showed that SP600125 reduced the numbers of both hair cells and supporting cells in neuromasts during larval development in a dose-dependent manner. Additionally, JNK inhibition strongly inhibited the proliferation of neuromast cells, which likely explains the decrease in the number of differentiated hair cells in inhibitor-treated larvae. Furthermore, western blot and in situ analysis showed that JNK inhibition induced cell cycle arrest through induction of p21 expression. We also showed that SP600125 induced cell death in developing neuromasts as measured by cleaved caspase-3 immunohistochemistry, and this was accompanied with an induction of p53 gene expression. Together these results indicate that JNK might be an important regulator in the development of hair cells in the lateral line in zebrafish by controlling both cell cycle progression and apoptosis. PMID- 26903806 TI - Astrocytes and Microglia and Their Potential Link with Autism Spectrum Disorders. AB - The cellular mechanism(s) underlying autism spectrum disorders (ASDs) are not fully understood although it has been shown that various genetic and environmental factors contribute to their etiology. As increasing evidence indicates that astrocytes and microglial cells play a major role in synapse maturation and function, and there is evidence of deficits in glial cell functions in ASDs, one current hypothesis is that glial dysfunctions directly contribute to their pathophysiology. The aim of this review is to summarize microglia and astrocyte functions in synapse development and their contributions to ASDs. PMID- 26903807 TI - Effects of PSA Removal from NCAM on the Critical Period Plasticity Triggered by the Antidepressant Fluoxetine in the Visual Cortex. AB - Neuronal plasticity peaks during critical periods of postnatal development and is reduced towards adulthood. Recent data suggests that windows of juvenile-like plasticity can be triggered in the adult brain by antidepressant drugs such as Fluoxetine. Although the exact mechanisms of how Fluoxetine promotes such plasticity remains unknown, several studies indicate that inhibitory circuits play an important role. The polysialylated form of the neural cell adhesion molecules (PSA-NCAM) has been suggested to mediate the effects of Fluoxetine and it is expressed in the adult brain by mature interneurons. Moreover, the enzymatic removal of PSA by neuroaminidase-N not only affects the structure of interneurons but also has been shown to play a role in the onset of critical periods during development. We have here used ocular dominance plasticity in the mouse visual cortex as a model to investigate whether removal of PSA might influence the Fluoxetine-induced plasticity. We demonstrate that PSA removal in the adult visual cortex alters neither the baseline ocular dominance, nor the fluoxetine-induced shift in the ocular dominance. We also show that both chronic Fluoxetine treatment and PSA removal independently increase the basal FosB expression in parvalbumin (PV) interneurons in the primary visual cortex. Therefore, our data suggest that although PSA-NCAM regulates inhibitory circuitry, it is not required for the reactivation of juvenile-like plasticity triggered by Fluoxetine. PMID- 26903808 TI - Expression of Lymphatic Markers in the Adult Rat Spinal Cord. AB - Under physiological conditions, lymphatic vessels are thought to be absent from the central nervous system (CNS), although they are widely distributed within the rest of the body. Recent work in the eye, i.e., another organ regarded as alymphatic, revealed numerous cells expressing lymphatic markers. As the latter can be involved in the response to pathological conditions, we addressed the presence of cells expressing lymphatic markers within the spinal cord by immunohistochemistry. Spinal cord of young adult Fisher rats was scrutinized for the co-expression of the lymphatic markers PROX1 and LYVE-1 with the cell type markers Iba1, CD68, PGP9.5, OLIG2. Rat skin served as positive control for the lymphatic markers. PROX1-immunoreactivity was detected in many nuclei throughout the spinal cord white and gray matter. These nuclei showed no association with LYVE-1. Expression of LYVE-1 could only be detected in cells at the spinal cord surface and in cells closely associated with blood vessels. These cells were found to co-express Iba1, a macrophage and microglia marker. Further, double labeling experiments using CD68, another marker found in microglia and macrophages, also displayed co-localization in the Iba1+ cells located at the spinal cord surface and those apposed to blood vessels. On the other hand, PROX1 expressing cells found in the parenchyma were lacking Iba1 or PGP9.5, but a significant fraction of those cells showed co-expression of the oligodendrocyte lineage marker OLIG2. Intriguingly, following spinal cord injury, LYVE-1 expressing cells assembled and reorganized into putative pre-vessel structures. As expected, the rat skin used as positive controls revealed classical lymphatic vessels, displaying PROX1+ nuclei surrounded by LYVE-1-immunoreactivity. Classical lymphatics were not detected in adult rat spinal cord. Nevertheless, numerous cells expressing either LYVE-1 or PROX1 were identified. Based on their localization and overlapping expression with Iba1, the LYVE-1+ cell population likely represents a macrophage subpopulation, while a significant fraction of PROX1+ cells belong to the oligodendrocytic lineage based on their distribution and the expression of OLIG2. The response of these LYVE-1+ and PROX1+ cell subpopulations to pathological conditions, especially in spinal cord inflammatory conditions, needs to be further elucidated. PMID- 26903810 TI - Aberrant Activity in Degenerated Retinas Revealed by Electrical Imaging. AB - In this review, I present and discuss the current understanding of aberrant electrical activity found in the ganglion cell layer (GCL) of rod-degenerated (rd) mouse retinas. The reported electrophysiological properties revealed by electrical imaging using high-density microelectrode arrays can be subdivided between spiking activity originating from retinal ganglion cells (RGCs) and local field potentials (LFPs) reflecting strong trans-membrane currents within the GCL. RGCs in rd retinas show increased and rhythmic spiking compared to age-matched wild-type retinas. Fundamental spiking frequencies range from 5 to 15 Hz in various mouse models. The rhythmic RGC spiking is driven by a presynaptic network comprising AII amacrine and bipolar cells. In the healthy retina this rhythm generating circuit is inhibited by photoreceptor input. A unique physiological feature of rd retinas is rhythmic LFP manifested as spatially-restricted low frequency (5-15 Hz) voltage changes. Their spatiotemporal characterization revealed propagation and correlation with RGC spiking. LFPs rely on gap junctional coupling and are shaped by glycinergic and by GABAergic transmission. The aberrant RGC spiking and LFPs provide a simple readout of the functionality of the remaining retinal circuitry which can be used in the development of improved vision restoration strategies. PMID- 26903811 TI - Corrigendum: Neurodegeneration and microtubule dynamics: death by a thousand cuts. AB - [This corrects the article on p. 343 in vol. 9, PMID: 26441521.]. PMID- 26903809 TI - Alterations in Mitochondrial Quality Control in Alzheimer's Disease. AB - Mitochondrial dysfunction is one of the earliest and most prominent features in the brains of Alzheimer's disease (AD) patients. Recent studies suggest that mitochondrial dysfunction plays a pivotal role in the pathogenesis of AD. Neurons are metabolically active cells, causing them to be particularly dependent on mitochondrial function for survival and maintenance. As highly dynamic organelles, mitochondria are characterized by a balance of fusion and fission, transport, and mitophagy, all of which are essential for maintaining mitochondrial integrity and function. Mitochondrial dynamics and mitophagy can therefore be identified as key pathways in mitochondrial quality control. Tremendous progress has been made in studying changes in these key aspects of mitochondrial biology in the vulnerable neurons of AD brains and mouse models, and the potential underlying mechanisms of such changes. This review highlights recent findings on alterations in the mitochondrial dynamics and mitophagy in AD and discusses how these abnormalities impact mitochondrial quality control and thus contribute to mitochondrial dysfunction in AD. PMID- 26903813 TI - Calmodulin Affects Sensitization of Drosophila melanogaster Odorant Receptors. AB - Flying insects have developed a remarkably sensitive olfactory system to detect faint and turbulent odor traces. This ability is linked to the olfactory receptors class of odorant receptors (ORs), occurring exclusively in winged insects. ORs form heteromeric complexes of an odorant specific receptor protein (OrX) and a highly conserved co-receptor protein (Orco). The ORs form ligand gated ion channels that are tuned by intracellular signaling systems. Repetitive subthreshold odor stimulation of olfactory sensory neurons sensitizes insect ORs. This OR sensitization process requires Orco activity. In the present study we first asked whether OR sensitization can be monitored with heterologously expressed OR proteins. Using electrophysiological and calcium imaging methods we demonstrate that D. melanogaster OR proteins expressed in CHO cells show sensitization upon repeated weak stimulation. This was found for OR channels formed by Orco as well as by Or22a or Or56a and Orco. Moreover, we show that inhibition of calmodulin (CaM) action on OR proteins, expressed in CHO cells, abolishes any sensitization. Finally, we investigated the sensitization phenomenon using an ex vivo preparation of olfactory sensory neurons (OSNs) expressing Or22a inside the fly's antenna. Using calcium imaging, we observed sensitization in the dendrites as well as in the soma. Inhibition of calmodulin with W7 disrupted the sensitization within the outer dendritic shaft, whereas the sensitization remained in the other OSN compartments. Taken together, our results suggest that CaM action is involved in sensitizing the OR complex and that this mechanisms accounts for the sensitization in the outer dendrites, whereas further mechanisms contribute to the sensitization observed in the other OSN compartments. The use of heterologously expressed OR proteins appears to be suitable for further investigations on the mechanistic basis of OR sensitization, while investigations on native neurons are required to study the presently unknown additional mechanisms involved in OSN sensitization. PMID- 26903814 TI - Hippocampal Hyperexcitability is Modulated by Microtubule-Active Agent: Evidence from In Vivo and In Vitro Epilepsy Models in the Rat. AB - The involvement of microtubule dynamics on bioelectric activity of neurons and neurotransmission represents a fascinating target of research in the context of neural excitability. It has been reported that alteration of microtubule cytoskeleton can lead to profound modifications of neural functioning, with a putative impact on hyperexcitability phenomena. Altogether, in the present study we pointed at exploring the outcomes of modulating the degree of microtubule polymerization in two electrophysiological models of epileptiform activity in the rat hippocampus. To this aim, we used in vivo maximal dentate activation (MDA) and in vitro hippocampal epileptiform bursting activity (HEBA) paradigms to assess the effects of nocodazole (NOC) and paclitaxel (PAC), that respectively destabilize and stabilize microtubule structures. In particular, in the MDA paroxysmal discharge is electrically induced, whereas the HEBA is obtained by altering extracellular ionic concentrations. Our results provided evidence that NOC 10 MUM was able to reduce the severity of MDA seizures, without inducing neurotoxicity as verified by the immunohistochemical assay. In some cases, paroxysmal discharge was completely blocked during the maximal effect of the drug. These data were also in agreement with the outcomes of in vitro HEBA, since NOC markedly decreased burst activity that was even silenced occasionally. In contrast, PAC at 10 MUM did not exert a clear action in both paradigms. The present study, targeting cellular mechanisms not much considered so far, suggests the possibility that microtubule-active drugs could modulate brain hyperexcitability. This contributes to the hypothesis that cytoskeleton function may affect synaptic processes, relapsing on bioelectric aspects of epileptic activity. PMID- 26903812 TI - Systematic Review of Pharmacological Properties of the Oligodendrocyte Lineage. AB - Oligodendrogenesis and oligodendrocyte precursor maturation are essential processes during the course of central nervous system development, and lead to the myelination of axons. Cells of the oligodendrocyte lineage are generated in the germinal zone from migratory bipolar oligodendrocyte precursor cells (OPCs), and acquire cell surface markers as they mature and respond specifically to factors which regulate proliferation, migration, differentiation, and survival. Loss of myelin underlies a wide range of neurological disorders, some of an autoimmune nature-multiple sclerosis probably being the most prominent. Current therapies are based on the use of immunomodulatory agents which are likely to promote myelin repair (remyelination) indirectly by subverting the inflammatory response, aspects of which impair the differentiation of OPCs. Cells of the oligodendrocyte lineage express and are capable of responding to a diverse array of ligand-receptor pairs, including neurotransmitters and nuclear receptors such as gamma-aminobutyric acid, glutamate, adenosine triphosphate, serotonin, acetylcholine, nitric oxide, opioids, prostaglandins, prolactin, and cannabinoids. The intent of this review is to provide the reader with a synopsis of our present state of knowledge concerning the pharmacological properties of the oligodendrocyte lineage, with particular attention to these receptor-ligand (i.e., neurotransmitters and nuclear receptor) interactions that can influence oligodendrocyte migration, proliferation, differentiation, and myelination, and an appraisal of their therapeutic potential. For example, many promising mediators work through Ca(2+) signaling, and the balance between Ca(2+) influx and efflux can determine the temporal and spatial properties of oligodendrocytes (OLs). Moreover, Ca(2+) signaling in OPCs can influence not only differentiation and myelination, but also process extension and migration, as well as cell death in mature mouse OLs. There is also evidence that oligodendroglia exhibit Ca(2+) transients in response to electrical activity of axons for activity-dependent myelination. Cholinergic antagonists, as well as endocannabinoid-related lipid signaling molecules target OLs. An understanding of such pharmacological pathways may thus lay the foundation to allow its leverage for therapeutic benefit in diseases of demyelination. PMID- 26903816 TI - Population Response Propagation to Extrastriate Areas Evoked by Intracortical Electrical Stimulation in V1. AB - The mouse visual system has multiple extrastriate areas surrounding V1 each with a distinct representation of the visual field and unique functional and connectivity profiles, which are believed to form two parallel processing streams, similar to the ventral and dorsal streams in primates. At the same time, mouse visual areas have a high degree of interconnectivity, in particular V1 sends input to all higher visual areas. The study of these direct connections can further our understanding of the cortical processing of visual signals in the early mammalian cortex. Several studies have been published about the anatomy of these connections, but an in vivo electrophysiological characterization and comparison of the transmission to multiple extrastriate areas has not yet been reported. We used intracortical electrical stimulation combined with RH1691 VSD imaging in adult C57BL/6 mice in urethane anesthesia to analyze interareal transmission from V1 to extrastriate areas in superficial cortical layers. We found seven extrastriate response sites (five lateral, two medial) in a spatial pattern similar to area maps of the mouse visual cortex and, by shifting the location of V1 stimulation, demonstrated that the evoked responses in LM and AL were in accordance with the visuotopic mappings of these areas known from anatomy and in vivo studies. These two sites, considered to be gateways to their processing streams, had shorter latencies and faster transmission speeds than other extrastriate response sites. Short latency differences between response sites, and that TTX injection into LM reduced but did not eliminate other extrastriate responses indicated that the evoked cortical activity was, at least partially, transmitted directly from V1 to extrastriate areas. This study reports on analysis of interareal transmission from V1 to multiple extrastriate areas in mouse using intracortical electrical stimulation in vivo. PMID- 26903815 TI - Long-term Potentiation at Temporoammonic Path-CA1 Synapses in Freely Moving Rats. AB - Hippocampal area CA1 receives direct entorhinal layer III input via the temporoammonic path (TAP) and recent studies implicate TAP-CA1 synapses are important for some aspects of hippocampal memory function. Nonetheless, as few studies have examined TAP-CA1 synaptic plasticity in vivo, the induction and longevity of TAP-CA1 long-term potentiation (LTP) has not been fully characterized. We analyzed CA1 responses following stimulation of the medial aspect of the angular bundle and investigated LTP at medial temporoammonic path (mTAP)-CA1 synapses in freely moving rats. We demonstrate monosynaptic mTAP-CA1 responses can be isolated in vivo as evidenced by observations of independent current sinks in the stratum lacunosum moleculare of both areas CA1 and CA3 following angular bundle stimulation. Contrasting prior indications that TAP input rarely elicits CA1 discharge, we observed mTAP-CA1 responses that appeared to contain putative population spikes in 40% of our behaving animals. Theta burst high frequency stimulation of mTAP afferents resulted in an input specific and N methyl-D-aspartate (NMDA) receptor-dependent LTP of mTAP-CA1 responses in behaving animals. LTP of mTAP-CA1 responses decayed as a function of two exponential decay curves with time constants (tau) of 2.7 and 148 days to decay 63.2% of maximal LTP. In contrast, mTAP-CA1 population spike potentiation longevity demonstrated a tau of 9.6 days. To our knowledge, these studies provide the first description of mTAP-CA1 LTP longevity in vivo. These data indicate TAP input to area CA1 is a physiologically relevant afferent system that displays robust synaptic plasticity. PMID- 26903817 TI - Glutamate and GABA in Vestibulo-Sympathetic Pathway Neurons. AB - The vestibulo-sympathetic reflex (VSR) actively modulates blood pressure during changes in posture. This reflex allows humans to stand up and quadrupeds to rear or climb without a precipitous decline in cerebral perfusion. The VSR pathway conveys signals from the vestibular end organs to the caudal vestibular nuclei. These cells, in turn, project to pre-sympathetic neurons in the rostral and caudal ventrolateral medulla (RVLM and CVLM, respectively). The present study assessed glutamate- and GABA-related immunofluorescence associated with central vestibular neurons of the VSR pathway in rats. Retrograde FluoroGold tract tracing was used to label vestibular neurons with projections to RVLM or CVLM, and sinusoidal galvanic vestibular stimulation (GVS) was employed to activate these pathways. Central vestibular neurons of the VSR were identified by co localization of FluoroGold and cFos protein, which accumulates in some vestibular neurons following galvanic stimulation. Triple-label immunofluorescence was used to co-localize glutamate- or GABA- labeling in the identified VSR pathway neurons. Most activated projection neurons displayed intense glutamate immunofluorescence, suggestive of glutamatergic neurotransmission. To support this, anterograde tracer was injected into the caudal vestibular nuclei. Vestibular axons and terminals in RVLM and CVLM co-localized the anterograde tracer and vesicular glutamate transporter-2 signals. Other retrogradely-labeled cFos-positive neurons displayed intense GABA immunofluorescence. VSR pathway neurons of both phenotypes were present in the caudal medial and spinal vestibular nuclei, and projected to both RVLM and CVLM. As a group, however, triple-labeled vestibular cells with intense glutamate immunofluorescence were located more rostrally in the vestibular nuclei than the GABAergic neurons. Only the GABAergic VSR pathway neurons showed a target preference, projecting predominantly to CVLM. These data provide the first demonstration of two disparate chemoanatomic VSR pathways. PMID- 26903818 TI - Anatomically Detailed and Large-Scale Simulations Studying Synapse Loss and Synchrony Using NeuroBox. AB - The morphology of neurons and networks plays an important role in processing electrical and biochemical signals. Based on neuronal reconstructions, which are becoming abundantly available through databases such as NeuroMorpho.org, numerical simulations of Hodgkin-Huxley-type equations, coupled to biochemical models, can be performed in order to systematically investigate the influence of cellular morphology and the connectivity pattern in networks on the underlying function. Development in the area of synthetic neural network generation and morphology reconstruction from microscopy data has brought forth the software tool NeuGen. Coupling this morphology data (either from databases, synthetic, or reconstruction) to the simulation platform UG 4 (which harbors a neuroscientific portfolio) and VRL-Studio, has brought forth the extendible toolbox NeuroBox. NeuroBox allows users to perform numerical simulations on hybrid-dimensional morphology representations. The code basis is designed in a modular way, such that e.g., new channel or synapse types can be added to the library. Workflows can be specified through scripts or through the VRL-Studio graphical workflow representation. Third-party tools, such as ImageJ, can be added to NeuroBox workflows. In this paper, NeuroBox is used to study the electrical and biochemical effects of synapse loss vs. synchrony in neurons, to investigate large morphology data sets within detailed biophysical simulations, and used to demonstrate the capability of utilizing high-performance computing infrastructure for large scale network simulations. Using new synapse distribution methods and Finite Volume based numerical solvers for compartment-type models, our results demonstrate how an increase in synaptic synchronization can compensate synapse loss at the electrical and calcium level, and how detailed neuronal morphology can be integrated in large-scale network simulations. PMID- 26903819 TI - Odor Experience Facilitates Sparse Representations of New Odors in a Large-Scale Olfactory Bulb Model. AB - Prior odor experience has a profound effect on the coding of new odor inputs by animals. The olfactory bulb, the first relay of the olfactory pathway, can substantially shape the representations of odor inputs. How prior odor experience affects the representation of new odor inputs in olfactory bulb and its underlying network mechanism are still unclear. Here we carried out a series of simulations based on a large-scale realistic mitral-granule network model and found that prior odor experience not only accelerated formation of the network, but it also significantly strengthened sparse responses in the mitral cell network while decreasing sparse responses in the granule cell network. This modulation of sparse representations may be due to the increase of inhibitory synaptic weights. Correlations among mitral cells within the network and correlations between mitral network responses to different odors decreased gradually when the number of prior training odors was increased, resulting in a greater decorrelation of the bulb representations of input odors. Based on these findings, we conclude that the degree of prior odor experience facilitates degrees of sparse representations of new odors by the mitral cell network through experience-enhanced inhibition mechanism. PMID- 26903821 TI - Oscillatory Activity in the Infant Brain and the Representation of Small Numbers. AB - Gamma-band oscillatory activity (GBA) is an established neural signature of sustained occluded object representation in infants and adults. However, it is not yet known whether the magnitude of GBA in the infant brain reflects the quantity of occluded items held in memory. To examine this, we compared GBA of 6 8 month-old infants during occlusion periods after the representation of two objects vs. that of one object. We found that maintaining a representation of two objects during occlusion resulted in significantly greater GBA relative to maintaining a single object. Further, this enhancement was located in the right occipital region, which is consistent with previous object representation research in adults and infants. We conclude that enhanced GBA reflects neural processes underlying infants' representation of small numbers. PMID- 26903822 TI - Traumatic Brain Injury Upregulates Phosphodiesterase Expression in the Hippocampus. AB - Traumatic brain injury (TBI) results in significant impairments in hippocampal synaptic plasticity. A molecule critically involved in hippocampal synaptic plasticity, 3',5'-cyclic adenosine monophosphate, is downregulated in the hippocampus after TBI, but the mechanism that underlies this decrease is unknown. To address this question, we determined whether phosphodiesterase (PDE) expression in the hippocampus is altered by TBI. Young adult male Sprague Dawley rats received sham surgery or moderate parasagittal fluid-percussion brain injury. Animals were analyzed by western blotting for changes in PDE expression levels in the hippocampus. We found that PDE1A levels were significantly increased at 30 min, 1 h and 6 h after TBI. PDE4B2 and 4D2 were also significantly increased at 1, 6, and 24 h after TBI. Additionally, phosphorylation of PDE4A was significantly increased at 6 and 24 h after TBI. No significant changes were observed in levels of PDE1B, 1C, 3A, 8A, or 8B between 30 min to 7 days after TBI. To determine the spatial profile of these increases, we used immunohistochemistry and flow cytometry at 24 h after TBI. PDE1A and phospho-PDE4A localized to neuronal cell bodies. PDE4B2 was expressed in neuronal dendrites, microglia and infiltrating CD11b(+) immune cells. PDE4D was predominantly found in microglia and infiltrating CD11b(+) immune cells. To determine if inhibition of PDE4 would improve hippocampal synaptic plasticity deficits after TBI, we treated hippocampal slices with rolipram, a pan-PDE4 inhibitor. Rolipram partially rescued the depression in basal synaptic transmission and converted a decaying form of long-term potentiation (LTP) into long-lasting LTP. Overall, these results identify several possible PDE targets for reducing hippocampal synaptic plasticity deficits and improving cognitive function acutely after TBI. PMID- 26903820 TI - Perisaccadic Updating of Visual Representations and Attentional States: Linking Behavior and Neurophysiology. AB - During natural vision, saccadic eye movements lead to frequent retinal image changes that result in different neuronal subpopulations representing the same visual feature across fixations. Despite these potentially disruptive changes to the neural representation, our visual percept is remarkably stable. Visual receptive field remapping, characterized as an anticipatory shift in the position of a neuron's spatial receptive field immediately before saccades, has been proposed as one possible neural substrate for visual stability. Many of the specific properties of remapping, e.g., the exact direction of remapping relative to the saccade vector and the precise mechanisms by which remapping could instantiate stability, remain a matter of debate. Recent studies have also shown that visual attention, like perception itself, can be sustained across saccades, suggesting that the attentional control system can also compensate for eye movements. Classical remapping could have an attentional component, or there could be a distinct attentional analog of visual remapping. At this time we do not yet fully understand how the stability of attentional representations relates to perisaccadic receptive field shifts. In this review, we develop a vocabulary for discussing perisaccadic shifts in receptive field location and perisaccadic shifts of attentional focus, review and synthesize behavioral and neurophysiological studies of perisaccadic perception and perisaccadic attention, and identify open questions that remain to be experimentally addressed. PMID- 26903825 TI - The Clock'N Test as a Possible Measure of Emotions: Normative Data Collected on a Non-clinical Population. AB - OBJECTIVE: At present emotional experience and implicit emotion regulation (IER) abilities are mainly assessed though self-reports, which are subjected to several biases. The aim of the present studies was to validate the Clock'N test, a recently developed time estimation task employing emotional priming to assess implicitly emotional reactivity and IER. METHODS: In Study 1, the Clock'N test was administered to 150 healthy participants with different age, laterality and gender, in order to ascertain whether these factors affected the test results. In phase 1 participant were asked to judge the duration of seven sounds. In phase 2, before judging the duration of the same sounds, participants were presented with short arousing video-clip used as emotional priming stimuli. Time warp was calculated as the difference in time estimation between phase 2 and phase 1, and used to assess how emotions affected subjective time estimations. In study 2, a representative sample was selected to provide normative scores to be employed to assess emotional reactivity (Score 1) and IER (Score 2), and to calculate statistical cutoffs, based on the 10th and 90th score distribution percentiles. RESULTS: Converging with previous findings, the results of study 1 suggested that the Clock'N test can be employed to assess both emotional reactivity, as indexed by an initial time underestimation, and IER, as indexed by a progressive shift to time overestimation. No effects of gender, age and laterality were found. CONCLUSIONS: These results suggest that the Clock'N test is adapted to assess emotional reactivity and IER. After collection of data on the test discriminant and convergent validity, this test may be employed to assess deficits in these abilities in different clinical populations. PMID- 26903824 TI - Hippocampal Neurophysiologic Changes after Mild Traumatic Brain Injury and Potential Neuromodulation Treatment Approaches. AB - Traumatic brain injury (TBI) is the leading cause of death and disability in individuals below age 45, and five million Americans live with chronic disability as a result. Mild TBI (mTBI), defined as TBI in the absence of major imaging or histopathological defects, is responsible for a majority of cases. Despite the lack of overt morphological defects, victims of mTBI frequently suffer lasting cognitive deficits, memory difficulties, and behavioral disturbances. There is increasing evidence that cognitive and memory dysfunction is related to subtle physiological changes that occur in the hippocampus, and these impact both the phenotype of deficits observed and subsequent recovery. Therapeutic modulation of physiological activity by means of medications commonly used for other indications or brain stimulation may represent novel treatment approaches. This review summarizes the present body of knowledge regarding neurophysiologic changes that occur in the hippocampus after mTBI, as well as potential targets for therapeutic modulation of neurologic activity. PMID- 26903823 TI - Spontaneous Neural Dynamics and Multi-scale Network Organization. AB - Spontaneous neural activity has historically been viewed as task-irrelevant noise that should be controlled for via experimental design, and removed through data analysis. However, electrophysiology and functional MRI studies of spontaneous activity patterns, which have greatly increased in number over the past decade, have revealed a close correspondence between these intrinsic patterns and the structural network architecture of functional brain circuits. In particular, by analyzing the large-scale covariation of spontaneous hemodynamics, researchers are able to reliably identify functional networks in the human brain. Subsequent work has sought to identify the corresponding neural signatures via electrophysiological measurements, as this would elucidate the neural origin of spontaneous hemodynamics and would reveal the temporal dynamics of these processes across slower and faster timescales. Here we survey common approaches to quantifying spontaneous neural activity, reviewing their empirical success, and their correspondence with the findings of neuroimaging. We emphasize invasive electrophysiological measurements, which are amenable to amplitude- and phase based analyses, and which can report variations in connectivity with high spatiotemporal precision. After summarizing key findings from the human brain, we survey work in animal models that display similar multi-scale properties. We highlight that, across many spatiotemporal scales, the covariance structure of spontaneous neural activity reflects structural properties of neural networks and dynamically tracks their functional repertoire. PMID- 26903827 TI - Trait Anxiety Modulates Brain Activity during Performance of Verbal Fluency Tasks. AB - Trait anxiety is thought to be associated with pathological anxiety, and a risk factor for psychiatric disorders. The present study examines the brain mechanisms associated with trait anxiety during the performing of verbal fluency tasks. The aim is to show how trait anxiety modulates executive functions as measured by verbal fluency, and to explore the link between verbal fluency and anxiety due to the putative negative biases in high-anxious individuals. Seven tasks of verbal fluency were used: letter "k," "f," verbs, "animals," "vehicles," "joy," and "fear." The results of 35 subjects (whole sample), and 17 subjects (nine men, eight women) selected from the whole sample for the low/high-anxious groups on the basis of Trait Anxiety scores were analyzed. The subjects were healthy, Polish speaking, right-handed and aged from 20 to 35 years old. fMRI (whole-brain analysis with FWE corrections) was used to show the neural signals under active participation in verbal fluency tasks. The results confirm that trait anxiety slightly modulates neural activation during the performance of verbal fluency tasks, especially in the more difficult tasks. Significant differences were found in brain activation during the performance of more complex tasks between individuals with low anxiety and those with high anxiety. Greater activation in the right hemisphere, frontal gyri, and cerebellum was found in people with low anxiety. The results reflect better integration of cognitive and affective capacities in individuals with low anxiety. PMID- 26903828 TI - The Neural Mechanisms of Social Learning from Fleeting Experience with Pain. AB - Social learning is critical for humans to adapt and cope with rapidly changing surroundings. Although, neuroscience has focused on associative learning and pain empathy, the neural mechanisms of social learning through fleeting pain remains to be determined. This functional MRI study included three participant groups, to investigate how the neuro-hemodynamic response and subjective evaluation in response to the observation of hand actions were modulated by first-hand experience (FH), as well as indirect experience through social-observational (SO), and verbal-informed (VI) learning from fleeting pain. The results indicated, that these three learning groups share the common neuro-hemodynamic activations in the brain regions implicated in emotional awareness, memory, mentalizing, perspective taking, and emotional regulation. The anterior insular cortex (AIC) was commonly activated during these learning procedures. The amygdala was only activated by the FH. Dynamic causal modeling further indicated, that the SO and VI learning exhibited weaker connectivity strength from the AIC to superior frontal gyrus than did the FH. These findings demonstrate, that social learning elicits distinct neural responses from associative learning. The ontogeny of human empathy could be better understood with social learning from fleeting experience with pain. PMID- 26903829 TI - Commentary: Understanding intentions from actions: Direct perception, inference, and the roles of mirror and mentalizing systems. PMID- 26903826 TI - Dietary Polyphenol Supplementation Prevents Alterations of Spatial Navigation in Middle-Aged Mice. AB - Spatial learning and memory deficits associated with hippocampal synaptic plasticity impairments are commonly observed during aging. Besides, the beneficial role of dietary polyphenols has been suggested as potential functional food candidates to prevent this memory decline. Indeed, polyphenols could potentiate the signaling pathways of synaptic plasticity underlying learning and memory. In this study, spatial learning deficits of middle-aged mice were first highlighted and characterized according to their navigation patterns in the Morris water maze task. An eight-week polyphenol-enriched diet, containing a polyphenol-rich extract from grape and blueberry (PEGB; from the Neurophenols Consortium) with high contents of flavonoids, stilbenes and phenolic acids, was then successful in reversing these age-induced effects. The use of spatial strategies was indeed delayed with aging whereas a polyphenol supplementation could promote the occurrence of spatial strategies. These behavioral results were associated with neurobiological changes: while the expression of hippocampal calmodulin kinase II (CaMKII) mRNA levels was reduced in middle-aged animals, the polyphenol-enriched diet could rescue them. Besides, an increased expression of nerve growth neurotrophic factor (NGF) mRNA levels was also observed in supplemented adult and middle-aged mice. Thus these data suggest that supplementation with polyphenols could be an efficient nutritional way to prevent age-induced cognitive decline. PMID- 26903830 TI - Learning about Time within the Spinal Cord II: Evidence that Temporal Regularity Is Encoded by a Spinal Oscillator. AB - How a stimulus impacts spinal cord function depends upon temporal relations. When intermittent noxious stimulation (shock) is applied and the interval between shock pulses is varied (unpredictable), it induces a lasting alteration that inhibits adaptive learning. If the same stimulus is applied in a temporally regular (predictable) manner, the capacity to learn is preserved and a protective/restorative effect is engaged that counters the adverse effect of variable stimulation. Sensitivity to temporal relations implies a capacity to encode time. This study explores how spinal neurons discriminate variable and fixed spaced stimulation. Communication with the brain was blocked by means of a spinal transection and adaptive capacity was tested using an instrumental learning task. In this task, subjects must learn to maintain a hind limb in a flexed position to minimize shock exposure. To evaluate the possibility that a distinct class of afferent fibers provide a sensory cue for regularity, we manipulated the temporal relation between shocks given to two dermatomes (leg and tail). Evidence for timing emerged when the stimuli were applied in a coherent manner across dermatomes, implying that a central (spinal) process detects regularity. Next, we show that fixed spaced stimulation has a restorative effect when half the physical stimuli are randomly omitted, as long as the stimuli remain in phase, suggesting that stimulus regularity is encoded by an internal oscillator Research suggests that the oscillator that drives the tempo of stepping depends upon neurons within the rostral lumbar (L1-L2) region. Disrupting communication with the L1-L2 tissue by means of a L3 transection eliminated the restorative effect of fixed spaced stimulation. Implications of the results for step training and rehabilitation after injury are discussed. PMID- 26903831 TI - Editorial: Avoidance: From Basic Science to Psychopathology. PMID- 26903833 TI - Self-Face Recognition in Schizophrenia: An Eye-Tracking Study. AB - Self-face recognition has been shown to be impaired in schizophrenia (SZ), according to studies using behavioral tasks implicating cognitive demands. Here, we employed an eye-tracking methodology, which is a relevant tool to understand impairments in self-face recognition deficits in SZ because it provides a natural, continuous and online record of face processing. Moreover, it allows collecting the most relevant and informative features each individual looks at during the self-face recognition. These advantages are especially relevant considering the fundamental role played by the patterns of visual exploration on face processing. Thus, this paper aims to investigate self-face recognition deficits in SZ using eye-tracking methodology. Visual scan paths were monitored in 20 patients with SZ and 20 healthy controls. Self, famous, and unknown faces were morphed in steps of 20%. Location, number, and duration of fixations on relevant areas were recorded with an eye-tracking system. Participants performed a passive exploration task (no specific instruction was provided), followed by an active decision making task (individuals were explicitly requested to recognize the different faces). Results showed that patients with SZ had fewer and longer fixations compared to controls. Nevertheless, both groups focused their attention on relevant facial features in a similar way. No significant difference was found between groups when participants were requested to recognize the faces (active task). In conclusion, using an eye tracking methodology and two tasks with low levels of cognitive demands, our results suggest that patients with SZ are able to: (1) explore faces and focus on relevant features of the face in a similar way as controls; and (2) recognize their own face. PMID- 26903832 TI - Can tDCS enhance item-specific effects and generalization after linguistically motivated aphasia therapy for verbs? AB - BACKGROUND: Aphasia therapy focusing on abstract properties of language promotes both item-specific effects and generalization to untreated materials. Neuromodulation with transcranial Direct Current Stimulation (tDCS) has been shown to enhance item-specific improvement, but its potential to enhance generalization has not been systematically investigated. Here, we test the efficacy of ACTION (a linguistically motivated protocol) and tDCS in producing item-specific and generalized improvement in aphasia. METHOD: Nine individuals with post-stroke aphasia participated in this study. Participants were pre-tested with a diagnostic language battery and a cognitive screening. Experimental tasks were administered over multiple baselines. Production of infinitives, of finite verbs and of full sentences were assessed before and after each treatment phase. Nonword repetition was used as a control measure. Each subject was treated in two phases. Ten daily 1-h treatment sessions were provided per phase, in a double blind, cross-over design. Linguistically-motivated language therapy focusing on verb inflection and sentence construction was provided in both phases. Each session began with 20 min of real or sham tDCS. Stimulation site was determined individually, based on MRI scans. RESULTS: Group data showed improved production of treated and untreated verbs, attesting the efficacy of behavioral treatment, and its potential to yield generalization. Each individual showed significant item-specific improvement. Generalization occurred in the first phase of treatment for all subjects, and in the second phase for two subjects. Stimulation effects at the group level were significant for treated and untreated verbs altogether, but a ceiling effect for Sham cannot be excluded, as scores between real tDCS and Sham differed only before treatment. CONCLUSION: Our data demonstrate the efficacy of ACTION and suggest that tDCS may enhance both item specific effects and generalization. PMID- 26903834 TI - The Development of Shared Liking of Representational but not Abstract Art in Primary School Children and Their Justifications for Liking. AB - Understanding how aesthetic preferences are shared among individuals, and its developmental time course, is a fundamental question in aesthetics. It has been shown that semantic associations, in response to representational artworks, overlap more strongly among individuals than those generated by abstract artworks and that the emotional valence of the associations also overlaps more for representational artworks. This valence response may be a key driver in aesthetic appreciation. The current study tested predictions derived from the semantic association account in a developmental context. Twenty 4-, 6-, 8- and 10-year-old children (n = 80) were shown 20 artworks (10 representational, 10 abstract) and were asked to rate each artwork and to explain their decision. Cross-observer agreement in aesthetic preferences increased with age from 4-8 years for both abstract and representational art. However, after age 6 the level of shared appreciation for representational and abstract artworks diverged, with significantly higher levels of agreement for representational than abstract artworks at age 8 and 10. The most common justifications for representational artworks involved subject matter, while for abstract artworks formal artistic properties and color were the most commonly used justifications. Representational artwork also showed a significantly higher proportion of associations and emotional responses than abstract artworks. In line with predictions from developmental cognitive neuroscience, references to the artist as an agent increased between ages 4 and 6 and again between ages 6 and 8, following the development of Theory of Mind. The findings support the view that increased experience with representational content during the life span reduces inter individual variation in aesthetic appreciation and increases shared preferences. In addition, brain and cognitive development appear to impact on art appreciation at milestone ages. PMID- 26903835 TI - Practicing Novel, Praxis-Like Movements: Physiological Effects of Repetition. AB - Our primary goal was to develop and validate a task that could provide evidence about how humans learn praxis gestures, such as those involving the use of tools. To that end, we created a video-based task in which subjects view a model performing novel, meaningless one-handed actions with kinematics similar to praxis gestures. Subjects then imitated the movements with their right hand. Trials were repeated six times to examine practice effects. EEG was recorded during the task. As a control, subjects watched videos of a model performing a well-established (over learned) tool-use gesture. These gestures were also imitated six times. Demonstrating convergent validity, EEG measures of task related cortical activation were similar in topography and frequency between the novel gesture task and the overlearned, praxis gesture task. As in studies assessing motor skill learning with simpler tasks, cortical activation during novel gesture learning decreased as the same gestures were repeated. In the control condition, repetition of overlearned tool-use gestures were also associated with reductions in activation, though to a lesser degree. Given that even overlearned, praxis gestures show constriction of EEG activity with repetition, it is possible that that attentional effects drive some of the repetition effects seen in EEG measures of activation during novel gesture repetition. PMID- 26903836 TI - Independence of Hot and Cold Executive Function Deficits in High-Functioning Adults with Autism Spectrum Disorder. AB - Individuals with autistic spectrum disorder (ASD) display diverse deficits in social, cognitive and behavioral functioning. To date, there has been mixed findings on the profile of executive function deficits for high-functioning adults (IQ > 70) with ASD. A conceptual distinction is commonly made between "cold" and "hot" executive functions. Cold executive functions refer to mechanistic higher-order cognitive operations (e.g., working memory), whereas hot executive functions entail cognitive abilities supported by emotional awareness and social perception (e.g., social cognition). This study aimed to determine the independence of deficits in hot and cold executive functions for high-functioning adults with ASD. Forty-two adults with ASD (64% male, aged 18-66 years) and 40 age and gender matched controls were administered The Awareness of Social Inference Test (TASIT; emotion recognition and social inference), Letter Number Sequencing (working memory) and Hayling Sentence Completion Test (response initiation and suppression). Between-group analyses identified that the ASD group performed significantly worse than matched controls on all measures of cold and hot executive functions (d = 0.54 - 1.5). Hierarchical multiple regression analyses revealed that the ASD sample performed more poorly on emotion recognition and social inference tasks than matched controls after controlling for cold executive functions and employment status. The findings also indicated that the ability to recognize emotions and make social inferences was supported by working memory and response initiation and suppression processes. Overall, this study supports the distinction between hot and cold executive function impairments for adults with ASD. Moreover, it advances understanding of higher order impairments underlying social interaction difficulties for this population which, in turn, may assist with diagnosis and inform intervention programs. PMID- 26903838 TI - Temporal, but not Directional, Prior Knowledge Shortens Muscle Reflex Latency in Response to Sudden Transition of Support Surface During Walking. AB - The central nervous system takes advantage of prior knowledge about potential upcoming perturbations for modulating postural reflexes. There are two distinct aspects of prior knowledge: spatial and temporal. This study investigated how each of spatial and temporal prior knowledge contributes to the shortening of muscle response latency. Eleven participants walked on a split-belt treadmill and perturbed by sudden acceleration or deceleration of the right belt at right foot contact. Spatial prior knowledge was given by instruction of possible direction (e.g., only acceleration) of upcoming perturbation at the beginning of an experimental session. Temporal prior knowledge was given to subjects by warning tones at foot contact during three consecutive strides before the perturbation. In response to acceleration perturbation, reflexive muscle activity was observed in soleus (SOL) and gastrocnemius (GAS) muscles. Onset latency of the GAS response was shorter (72 ms vs. 58 ms) when subjects knew the timing of the upcoming perturbation, whereas the latency was independent of directional prior knowledge. SOL onset latency (44 ms) was not influenced by directional nor temporal prior knowledge. Although spinal neural circuit that mediates short latency reflex was not influenced by the prior knowledge, excitability in supra spinal neural circuit that mediates medium- and long-latency reflex might be enhanced by knowing the timing of the upcoming perturbation. PMID- 26903839 TI - Response: "Newborn chicks need no number tricks. Commentary: Number-space mapping in the newborn chick resembles humans' mental number line". PMID- 26903837 TI - How Transcranial Direct Current Stimulation Can Modulate Implicit Motor Sequence Learning and Consolidation: A Brief Review. AB - The purpose of this review is to investigate how transcranial direct current stimulation (tDCS) can modulate implicit motor sequence learning and consolidation. So far, most of the studies have focused on the modulating effect of tDCS for explicit motor learning. Here, we focus explicitly on implicit motor sequence learning and consolidation in order to improve our understanding about the potential of tDCS to affect this kind of unconscious learning. Specifically, we concentrate on studies with the serial reaction time task (SRTT), the classical paradigm for measuring implicit motor sequence learning. The influence of tDCS has been investigated for the primary motor cortex, the premotor cortex, the prefrontal cortex, and the cerebellum. The results indicate that tDCS above the primary motor cortex gives raise to the most consistent modulating effects for both implicit motor sequence learning and consolidation. PMID- 26903840 TI - Editorial: Facing the Other: Novel Theories and Methods in Face Perception Research. PMID- 26903841 TI - Transcranial Direct Current Stimulation Modulates Neuronal Activity and Learning in Pilot Training. AB - Skill acquisition requires distributed learning both within (online) and across (offline) days to consolidate experiences into newly learned abilities. In particular, piloting an aircraft requires skills developed from extensive training and practice. Here, we tested the hypothesis that transcranial direct current stimulation (tDCS) can modulate neuronal function to improve skill learning and performance during flight simulator training of aircraft landing procedures. Thirty-two right-handed participants consented to participate in four consecutive daily sessions of flight simulation training and received sham or anodal high-definition-tDCS to the right dorsolateral prefrontal cortex (DLPFC) or left motor cortex (M1) in a randomized, double-blind experiment. Continuous electroencephalography (EEG) and functional near infrared spectroscopy (fNIRS) were collected during flight simulation, n-back working memory, and resting-state assessments. tDCS of the right DLPFC increased midline-frontal theta-band activity in flight and n-back working memory training, confirming tDCS-related modulation of brain processes involved in executive function. This modulation corresponded to a significantly different online and offline learning rates for working memory accuracy and decreased inter-subject behavioral variability in flight and n-back tasks in the DLPFC stimulation group. Additionally, tDCS of left M1 increased parietal alpha power during flight tasks and tDCS to the right DLPFC increased midline frontal theta-band power during n-back and flight tasks. These results demonstrate a modulation of group variance in skill acquisition through an increasing in learned skill consistency in cognitive and real-world tasks with tDCS. Further, tDCS performance improvements corresponded to changes in electrophysiological and blood-oxygenation activity of the DLPFC and motor cortices, providing a stronger link between modulated neuronal function and behavior. PMID- 26903842 TI - Chronic Post-Concussion Neurocognitive Deficits. I. Relationship with White Matter Integrity. AB - We previously identified visual tracking deficits and associated degradation of integrity in specific white matter tracts as characteristics of concussion. We re explored these characteristics in adult patients with persistent post-concussive symptoms using independent new data acquired during 2009-2012. Thirty-two patients and 126 normal controls underwent cognitive assessments and MR-DTI. After data collection, a subset of control subjects was selected to be individually paired with patients based on gender and age. We identified patients' cognitive deficits through pairwise comparisons between patients and matched control subjects. Within the remaining 94 normal subjects, we identified white matter tracts whose integrity correlated with metrics that indicated performance degradation in patients. We then tested for reduced integrity in these white matter tracts in patients relative to matched controls. Most patients showed no abnormality in MR images unlike the previous study. Patients' visual tracking was generally normal. Patients' response times in an attention task were slowed, but could not be explained as reduced integrity of white matter tracts relating to normal response timing. In the present patient cohort, we did not observe behavioral or anatomical deficits that we previously identified as characteristic of concussion. The recent cohort likely represented those with milder injury compared to the earlier cohort. The discrepancy may be explained by a change in the patient recruitment pool circa 2007 associated with an increase in public awareness of concussion. PMID- 26903844 TI - The Frog Test: A Tool for Measuring Humor Theories' Validity and Humor Preferences. PMID- 26903845 TI - Alpha-Band Oscillations Reflect Altered Multisensory Processing of the McGurk Illusion in Schizophrenia. AB - The formation of coherent multisensory percepts requires integration of stimuli across the multiple senses. Patients with schizophrenia (ScZ) often experience a loss of coherent perception and hence, they might also show dysfunctional multisensory processing. In this high-density electroencephalography study, we investigated the neural signatures of the McGurk illusion, as a phenomenon of speech-specific multisensory processing. In the McGurk illusion lip movements are paired with incongruent auditory syllables, which can induce a fused percept. In ScZ patients and healthy controls we compared neural oscillations and event related potentials (ERPs) to congruent audiovisual speech stimuli and McGurk illusion trials, where a visual /ga/ and an auditory /pa/ was often perceived as /ka/. There were no significant group differences in illusion rates. The EEG data analysis revealed larger short latency ERPs to McGurk illusion compared with congruent trials in controls. The reversed effect pattern was found in ScZ patients, indicating an early audiovisual processing deficit. Moreover, we observed stronger suppression of medio-central alpha-band power (8-10 Hz, 550-700 ms) in response to McGurk illusion compared with control trials in the control group. Again, the reversed pattern was found in SCZ patients. Moreover, within groups, alpha-band suppression was negatively correlated with the McGurk illusion rate in ScZ patients, while the correlation tended to be positive in controls. The topography of alpha-band effects indicated an involvement of auditory and/or frontal structures. Our study suggests that short latency ERPs and long latency alpha-band oscillations reflect abnormal multisensory processing of the McGurk illusion in ScZ. PMID- 26903846 TI - Statistical Regularities Attract Attention when Task-Relevant. AB - Visual attention seems essential for learning the statistical regularities in our environment, a process known as statistical learning. However, how attention is allocated when exploring a novel visual scene whose statistical structure is unknown remains unclear. In order to address this question, we investigated visual attention allocation during a task in which we manipulated the conditional probability of occurrence of colored stimuli, unbeknown to the subjects. Participants were instructed to detect a target colored dot among two dots moving along separate circular paths. We evaluated implicit statistical learning, i.e., the effect of color predictability on reaction times (RTs), and recorded eye position concurrently. Attention allocation was indexed by comparing the Mahalanobis distance between the position, velocity and acceleration of the eyes and the two colored dots. We found that learning the conditional probabilities occurred very early during the course of the experiment as shown by the fact that, starting already from the first block, predictable stimuli were detected with shorter RT than unpredictable ones. In terms of attentional allocation, we found that the predictive stimulus attracted gaze only when it was informative about the occurrence of the target but not when it predicted the occurrence of a task-irrelevant stimulus. This suggests that attention allocation was influenced by regularities only when they were instrumental in performing the task. Moreover, we found that the attentional bias towards task-relevant predictive stimuli occurred at a very early stage of learning, concomitantly with the first effects of learning on RT. In conclusion, these results show that statistical regularities capture visual attention only after a few occurrences, provided these regularities are instrumental to perform the task. PMID- 26903843 TI - The Representation of Objects in Apraxia: From Action Execution to Error Awareness. AB - Apraxia is a well-known syndrome characterized by the sufferer's inability to perform routine gestures. In an attempt to understand the syndrome better, various different theories have been developed and a number of classifications of different subtypes have been proposed. In this article review, we will address these theories with a specific focus on how the use of objects helps us to better understand upper limb apraxia. With this aim, we will consider transitive vs. intransitive action dissociation as well as less frequent types of apraxia involving objects, i.e., constructive apraxia and magnetic apraxia. Pantomime and the imitation of objects in use are also considered with a view to dissociating the various different components involved in upper limb apraxia. Finally, we discuss the evidence relating to action recognition and awareness of errors in the execution of actions. Various different components concerning the use of objects emerge from our analysis and the results show that knowledge of an object and sensory-motor representations are supported by other functions such as spatial and body representations, executive functions and monitoring systems. PMID- 26903847 TI - Semantic Stability is More Pleasurable in Unstable Episodic Contexts. On the Relevance of Perceptual Challenge in Art Appreciation. AB - Research in the field of psychological aesthetics points to the appeal of stimuli which defy easy recognition by being "semantically unstable" but which still allow for creating meaning-in the ongoing process of elaborative perception or as an end product of the entire process. Such effects were reported for hidden images (Muth and Carbon, 2013) as well as Cubist artworks concealing detectable although fragmented-objects (Muth et al., 2013). To test the stability of the relationship between semantic determinacy and appreciation across different episodic contexts, 30 volunteers evaluated an artistic movie continuously on visual determinacy or liking via the Continuous Evaluation Procedure (CEP, Muth et al., 2015b). The movie consisted of five episodes with emerging Gestalts. In the first between-participants condition, the hidden Gestalts in the movie episodes were of increasing determinacy, in the second condition, the episodes showed decreasing determinacies of hidden Gestalts. In the increasing-determinacy group, visual determinacy was rated higher and showed better predictive quality for liking than in the decreasing-determinacy group. Furthermore, when the movie started with low visual determinacy of hidden Gestalts, unexpectedly strong increases in visual determinacy had a bigger effect on liking than in the condition which allowed for weaker Gestalt recognition after having started with highly determinate Gestalts. The resulting pattern calls for consideration of the episodic context when examining art appreciation. PMID- 26903849 TI - Bootstrap Signal-to-Noise Confidence Intervals: An Objective Method for Subject Exclusion and Quality Control in ERP Studies. AB - Analysis of event-related potential (ERP) data includes several steps to ensure that ERPs meet an appropriate level of signal quality. One such step, subject exclusion, rejects subject data if ERP waveforms fail to meet an appropriate level of signal quality. Subject exclusion is an important quality control step in the ERP analysis pipeline as it ensures that statistical inference is based only upon those subjects exhibiting clear evoked brain responses. This critical quality control step is most often performed simply through visual inspection of subject-level ERPs by investigators. Such an approach is qualitative, subjective, and susceptible to investigator bias, as there are no standards as to what constitutes an ERP of sufficient signal quality. Here, we describe a standardized and objective method for quantifying waveform quality in individual subjects and establishing criteria for subject exclusion. The approach uses bootstrap resampling of ERP waveforms (from a pool of all available trials) to compute a signal-to-noise ratio confidence interval (SNR-CI) for individual subject waveforms. The lower bound of this SNR-CI (SNRLB ) yields an effective and objective measure of signal quality as it ensures that ERP waveforms statistically exceed a desired signal-to-noise criterion. SNRLB provides a quantifiable metric of individual subject ERP quality and eliminates the need for subjective evaluation of waveform quality by the investigator. We detail the SNR CI methodology, establish the efficacy of employing this approach with Monte Carlo simulations, and demonstrate its utility in practice when applied to ERP datasets. PMID- 26903848 TI - Temporal Cortex Activation to Audiovisual Speech in Normal-Hearing and Cochlear Implant Users Measured with Functional Near-Infrared Spectroscopy. AB - BACKGROUND: Speech understanding may rely not only on auditory, but also on visual information. Non-invasive functional neuroimaging techniques can expose the neural processes underlying the integration of multisensory processes required for speech understanding in humans. Nevertheless, noise (from functional MRI, fMRI) limits the usefulness in auditory experiments, and electromagnetic artifacts caused by electronic implants worn by subjects can severely distort the scans (EEG, fMRI). Therefore, we assessed audio-visual activation of temporal cortex with a silent, optical neuroimaging technique: functional near-infrared spectroscopy (fNIRS). METHODS: We studied temporal cortical activation as represented by concentration changes of oxy- and deoxy-hemoglobin in four, easy to-apply fNIRS optical channels of 33 normal-hearing adult subjects and five post lingually deaf cochlear implant (CI) users in response to supra-threshold unisensory auditory and visual, as well as to congruent auditory-visual speech stimuli. RESULTS: Activation effects were not visible from single fNIRS channels. However, by discounting physiological noise through reference channel subtraction (RCS), auditory, visual and audiovisual (AV) speech stimuli evoked concentration changes for all sensory modalities in both cohorts (p < 0.001). Auditory stimulation evoked larger concentration changes than visual stimuli (p < 0.001). A saturation effect was observed for the AV condition. CONCLUSIONS: Physiological, systemic noise can be removed from fNIRS signals by RCS. The observed multisensory enhancement of an auditory cortical channel can be plausibly described by a simple addition of the auditory and visual signals with saturation. PMID- 26903851 TI - Measuring the Performance of Neural Models. AB - Good metrics of the performance of a statistical or computational model are essential for model comparison and selection. Here, we address the design of performance metrics for models that aim to predict neural responses to sensory inputs. This is particularly difficult because the responses of sensory neurons are inherently variable, even in response to repeated presentations of identical stimuli. In this situation, standard metrics (such as the correlation coefficient) fail because they do not distinguish between explainable variance (the part of the neural response that is systematically dependent on the stimulus) and response variability (the part of the neural response that is not systematically dependent on the stimulus, and cannot be explained by modeling the stimulus-response relationship). As a result, models which perfectly describe the systematic stimulus-response relationship may appear to perform poorly. Two metrics have previously been proposed which account for this inherent variability: Signal Power Explained (SPE, Sahani and Linden, 2003), and the normalized correlation coefficient (CC norm , Hsu et al., 2004). Here, we analyze these metrics, and show that they are intimately related. However, SPE has no lower bound, and we show that, even for good models, SPE can yield negative values that are difficult to interpret. CC norm is better behaved in that it is effectively bounded between -1 and 1, and values below zero are very rare in practice and easy to interpret. However, it was hitherto not possible to calculate CC norm directly; instead, it was estimated using imprecise and laborious resampling techniques. Here, we identify a new approach that can calculate CC norm quickly and accurately. As a result, we argue that it is now a better choice of metric than SPE to accurately evaluate the performance of neural models. PMID- 26903850 TI - A Phenomenological Model of the Electrically Stimulated Auditory Nerve Fiber: Temporal and Biphasic Response Properties. AB - We present a phenomenological model of electrically stimulated auditory nerve fibers (ANFs). The model reproduces the probabilistic and temporal properties of the ANF response to both monophasic and biphasic stimuli, in isolation. The main contribution of the model lies in its ability to reproduce statistics of the ANF response (mean latency, jitter, and firing probability) under both monophasic and cathodic-anodic biphasic stimulation, without changing the model's parameters. The response statistics of the model depend on stimulus level and duration of the stimulating pulse, reproducing trends observed in the ANF. In the case of biphasic stimulation, the model reproduces the effects of pseudomonophasic pulse shapes and also the dependence on the interphase gap (IPG) of the stimulus pulse, an effect that is quantitatively reproduced. The model is fitted to ANF data using a procedure that uniquely determines each model parameter. It is thus possible to rapidly parameterize a large population of neurons to reproduce a given set of response statistic distributions. Our work extends the stochastic leaky integrate and fire (SLIF) neuron, a well-studied phenomenological model of the electrically stimulated neuron. We extend the SLIF neuron so as to produce a realistic latency distribution by delaying the moment of spiking. During this delay, spiking may be abolished by anodic current. By this means, the probability of the model neuron responding to a stimulus is reduced when a trailing phase of opposite polarity is introduced. By introducing a minimum wait period that must elapse before a spike may be emitted, the model is able to reproduce the differences in the threshold level observed in the ANF for monophasic and biphasic stimuli. Thus, the ANF response to a large variety of pulse shapes are reproduced correctly by this model. PMID- 26903852 TI - The Development and Analysis of Integrated Neuroscience Data. AB - There is a strong emphasis on developing novel neuroscience technologies, in particular on recording from more neurons. There has thus been increasing discussion about how to analyze the resulting big datasets. What has received less attention is that over the last 30 years, papers in neuroscience have progressively integrated more approaches, such as electrophysiology, anatomy, and genetics. As such, there has been little discussion on how to combine and analyze this multimodal data. Here, we describe the growth of multimodal approaches, and discuss the needed analysis advancements to make sense of this data. PMID- 26903853 TI - Diffantom: Whole-Brain Diffusion MRI Phantoms Derived from Real Datasets of the Human Connectome Project. PMID- 26903854 TI - The iTRAPs: Guardians of Synaptic Vesicle Cargo Retrieval During Endocytosis. AB - The reformation of synaptic vesicles (SVs) during endocytosis is essential for the maintenance of neurotransmission in central nerve terminals. Newly formed SVs must be generated with the correct protein cargo in the correct stoichiometry to be functional for exocytosis. Classical clathrin adaptor protein complexes play a key role in sorting and clustering synaptic vesicle cargo in this regard. However it is becoming increasingly apparent that additional "fail-safe" mechanisms exist to ensure the accurate retrieval of essential cargo molecules. For example, the monomeric adaptor proteins AP180/CALM and stonin-2 are required for the efficient retrieval of synaptobrevin II (sybII) and synaptotagmin-1 respectively. Furthermore, recent studies have revealed that sybII and synaptotagmin-1 interact with other SV cargoes to ensure a high fidelity of retrieval. These cargoes are synaptophysin (for sybII) and SV2A (for synaptotagmin-1). In this review, we summarize current knowledge regarding the retrieval mechanisms for both sybII and synaptotagmin-1 during endocytosis. We also define and set criteria for a new functional group of SV molecules that facilitate the retrieval of their interaction partners. We have termed these molecules intrinsic trafficking partners (iTRAPs) and we discuss how the function of this group impacts on presynaptic performance in both health and disease. PMID- 26903855 TI - Presynaptic Molecular Determinants of Quantal Size. AB - The quantal hypothesis for the release of neurotransmitters at the chemical synapse has gained wide acceptance since it was first worked out at the motor endplate in frog skeletal muscle in the 1950's. Considering the morphological identification of synaptic vesicles (SVs) at the nerve terminals that appeared to be homogeneous in size, the hypothesis proposed that signal transduction at synapses is mediated by the release of neurotransmitters packed in SVs that are individually uniform in size; the amount of transmitter in a synaptic vesicle is called a quantum. Although quantal size-the amplitude of the postsynaptic response elicited by the release of neurotransmitters from a single vesicle clearly depends on the number and sensitivity of the postsynaptic receptors, accumulating evidence has also indicated that the amount of neurotransmitters stored in SVs can be altered by various presynaptic factors. Here, I provide an overview of the concepts and underlying presynaptic molecular underpinnings that may regulate quantal size. PMID- 26903856 TI - The Roles of Microtubule-Based Transport at Presynaptic Nerve Terminals. AB - Targeted intracellular movement of presynaptic proteins plays important roles during synapse formation and, later, in the homeostatic maintenance of mature synapses. Movement of these proteins, often as vesicular packages, is mediated by motor complexes travelling along intracellular cytoskeletal networks. Presynaptic protein transport by kinesin motors in particular plays important roles during synaptogenesis to bring newly synthesized proteins to establish nascent synaptic sites. Conversely, movement of proteins away from presynaptic sites by Dynein motors enables synapse-nuclear signaling and allows for synaptic renewal through degradation of unwanted or damaged proteins. Remarkably, recent data has indicated that synaptic and protein trafficking machineries can modulate each other's functions. Here, we survey the mechanisms involved in moving presynaptic components to and away from synapses and how this process supports presynaptic function. PMID- 26903857 TI - Diagnostic Value of microRNA for Alzheimer's Disease: A Systematic Review and Meta-Analysis. AB - Sound evidence indicates that microRNAs (miRNAs) are aberrantly expressed in Alzheimer's disease (AD) patients. We performed a systematic review and meta analysis to investigate the role of miRNA in AD pathogenesis and their clinical diagnostic value; a systematic review of literature and meta-analysis of clinical trials were performed. In the systematic review, 236 papers were included, and we reviewed the dysregulated miRNA expression in different parts of AD patients in order to identify the relationship between aberrantly expressed miRNAs and AD pathology. In the subsequent meta-analysis, seven studies were statistically analyzed with the following results: pooled sensitivity 0.86 (95%CI 0.79-0.90), pooled specificity 0.87 (95%CI 0.72-0.95), diagnostic odds ratio (28.29), and the area under the curve (0.87). In conclusion, our review indicated that aberrant expression of various miRNAs plays an important role in the pathological process of AD, and statistical analysis of quantitative studies reveal the potential value of specific miRNAs in the diagnosis of AD. PMID- 26903858 TI - Alzheimer's Biomarkers are Correlated with Brain Connectivity in Older Adults Differentially during Resting and Task States. AB - beta-amyloid (Abeta) plaques and tau-related neurodegeneration are pathologic hallmarks of Alzheimer's disease (AD). The utility of AD biomarkers, including those measured in cerebrospinal fluid (CSF), in predicting future AD risk and cognitive decline is still being refined. Here, we explored potential relationships between functional connectivity (FC) patterns within the default mode network (DMN), age, CSF biomarkers (Abeta42 and pTau181), and cognitive status in older adults. Multiple measures of FC were explored, including a novel time series-based measure [total interdependence (TI)]. In our sample of 27 cognitively normal older adults, no significant associations were found between levels of Abeta42 or pTau181 and cognitive scores or regional brain volumes. However, we observed several novel relationships between these biomarkers and measures of FC in DMN during both resting-state and a short-term memory task. First, increased connectivity between bilateral anterior middle temporal gyri was associated with higher levels of CSF Abeta42 and Abeta42/pTau181 ratio (reflecting lower AD risk) during both rest and task. Second, increased bilateral parietal connectivity during the short-term memory task, but not during rest, was associated with higher levels of CSF pTau181 (reflecting higher AD risk). Third, increased connectivity between left middle temporal and left parietal cortices during the active task was associated with decreased global cognitive status but not CSF biomarkers. Lastly, we found that our new TI method was more sensitive to the CSF Abeta42-connectivity relationship whereas the traditional cross correlation method was more sensitive to levels of CSF pTau181 and cognitive status. With further refinement, resting-state connectivity and task-driven connectivity measures hold promise as non-invasive neuroimaging markers of Abeta and pTau burden in cognitively normal older adults. PMID- 26903859 TI - Neural Signaling of Food Healthiness Associated with Emotion Processing. AB - The ability to differentiate healthy from unhealthy foods is important in order to promote good health. Food, however, may have an emotional connotation, which could be inversely related to healthiness. The neurobiological background of differentiating healthy and unhealthy food and its relations to emotion processing are not yet well understood. We addressed the neural activations, particularly considering the single subject level, when one evaluates a food item to be of a higher, compared to a lower grade of healthiness with a particular view on emotion processing brain regions. Thirty-seven healthy subjects underwent functional magnetic resonance imaging while evaluating the healthiness of food presented as photographs with a subsequent rating on a visual analog scale. We compared individual evaluations of high and low healthiness of food items and also considered gender differences. We found increased activation when food was evaluated to be healthy in the left dorsolateral prefrontal cortex and precuneus in whole brain analyses. In ROI analyses, perceived and rated higher healthiness was associated with lower amygdala activity and higher ventral striatal and orbitofrontal cortex activity. Females exerted a higher activation in midbrain areas when rating food items as being healthy. Our results underline the close relationship between food and emotion processing, which makes sense considering evolutionary aspects. Actively evaluating and deciding whether food is healthy is accompanied by neural signaling associated with reward and self-relevance, which could promote salutary nutrition behavior. The involved brain regions may be amenable to mechanisms of emotion regulation in the context of psychotherapeutic regulation of food intake. PMID- 26903861 TI - A Simulation Model of Periarterial Clearance of Amyloid-beta from the Brain. AB - The accumulation of soluble and insoluble amyloid-beta (Abeta) in the brain indicates failure of elimination of Abeta from the brain with age and Alzheimer's disease (AD). There is a variety of mechanisms for elimination of Abeta from the brain. They include the action of microglia and enzymes together with receptor mediated absorption of Abeta into the blood and periarterial lymphatic drainage of Abeta. Although the brain possesses no conventional lymphatics, experimental studies have shown that fluid and solutes, such as Abeta, are eliminated from the brain along 100 nm wide basement membranes in the walls of cerebral capillaries and arteries. This lymphatic drainage pathway is reflected in the deposition of Abeta in the walls of human arteries with age and AD as cerebral amyloid angiopathy (CAA). Initially, Abeta diffuses through the extracellular spaces of gray matter in the brain and then enters basement membranes in capillaries and arteries to flow out of the brain. Although diffusion through the extracellular spaces of the brain has been well characterized, the exact mechanism whereby perivascular elimination of Abeta occurs has not been resolved. Here we use a computational model to describe the process of periarterial drainage in the context of diffusion in the brain, demonstrating that periarterial drainage along basement membranes is very rapid compared with diffusion. Our results are a validation of experimental data and are significant in the context of failure of periarterial drainage as a mechanism underlying the pathogenesis of AD as well as complications associated with its immunotherapy. PMID- 26903860 TI - Frontotemporal Lobar Degeneration and MicroRNAs. AB - Frontotemporal lobar degeneration (FTLD) includes a spectrum of disorders characterized by changes of personality and social behavior and, often, a gradual and progressive language dysfunction. In the last years, several efforts have been fulfilled in identifying both genetic mutations and pathological proteins associated with FTLD. The molecular bases undergoing the onset and progression of the disease remain still unknown. Recent literature prompts an involvement of RNA metabolism in FTLD, particularly microRNAs (miRNAs). Dysregulation of miRNAs in several disorders, including neurodegenerative diseases, and increasing importance of circulating miRNAs in different pathologies has suggested to implement the study of their possible application as biological markers and new therapeutic targets; moreover, miRNA-based therapy is becoming a powerful tool to deepen the function of a gene, the mechanism of a disease, and validate therapeutic targets. Regarding FTLD, different studies showed that miRNAs are playing an important role. For example, several reports have evaluated miRNA regulation of the progranulin gene suggesting that it is under their control, as described for miR-29b, miR-107, and miR-659. More recently, it has been demonstrated that TMEM106B gene, which protein is elevated in FTLD-TDP brains, is repressed by miR-132/212 cluster; this post-transcriptional mechanism increases intracellular levels of progranulin, affecting its pathways. These findings if confirmed could suggest that these microRNAs have a role as potential targets for some related-FTLD genes. In this review, we focus on the emerging roles of the miRNAs in the pathogenesis of FTLD. PMID- 26903862 TI - The Neurocognitive Basis for Impaired Dual-Task Performance in Senior Fallers. AB - Falls are a major health-care concern, and while dual-task performance is widely recognized as being impaired in those at-risk for falls, the underlying neurocognitive mechanisms remain unknown. A better understanding of the underlying mechanisms could lead to the refinement and development of behavioral, cognitive, or neuropharmacological interventions for falls prevention. Therefore, we conducted a cross-sectional study with community-dwelling older adults aged 70 80 years with a history of falls (i.e., two or more falls in the past 12 months) or no history of falls (i.e., zero falls in the past 12 months); n = 28 per group. We compared functional activation during cognitive-based dual-task performance between fallers and non-fallers using functional magnetic resonance imaging (fMRI). Executive cognitive functioning was assessed via Stroop, Trail Making, and Digit Span. Mobility was assessed via the Timed Up and Go test (TUG). We found that non-fallers exhibited significantly greater functional activation compared with fallers during dual-task performance in key regions responsible for resolving dual-task interference, including precentral, postcentral, and lingual gyri. Further, we report slower reaction times during dual-task performance in fallers and significant correlations between level of functional activation and independent measures of executive cognitive functioning and mobility. Our study is the first neuroimaging study to examine dual-task performance in fallers, and supports the notion that fallers have reduced functional brain activation compared with non-fallers. Given that dual-task performance-and the underlying neural concomitants-appears to be malleable with relevant training, our study serves as a launching point for promising strategies to reduce falls in the future. PMID- 26903864 TI - Selected Topical Agents Used in Traditional Chinese Medicine in the Treatment of Minor Injuries- A Review. AB - Topical medicinal patches have been popular for the treatment of minor injuries like sprains and avulsions. Other inflammatory conditions like chronic musculo tendinous pain and or fasciitis are also taken care of by local ointments or rubs. In the oriental communities, medicinal herbs frequently form the major components of the patches. In spite of the lack of scientific evidence of efficacy, the popularity of such traditional application persists for centuries. In this era of evidence-based clinical treatment, there is an urgent need to look into this traditional practice. The purpose should include a scientific verification of the efficacy of the practice, and once proven, further explorations would be indicated to bring the practice to a higher level. A system of comprehensive exploration was proposed and practiced in the past years to fulfill the aspiration. The research consisted of four areas: (1) Identification of the suitable medicinal herbs for the topical study; (2) Study of the biological activities of the selected herbs, concentrating on the areas of anti inflammation, anti-oxidation, angiogenesis and cellular proliferation; (3) Study on the transcutaneous transport of the chemicals of the selected herbs to deeper tissues; and (4) Pilot clinical studies on common superficial inflammatory musculo-skeletal conditions to give objective clinical evidences to the topical applications. Five herbs were identified as suitable candidates of study. They were put into relevant laboratory platforms and were proven to be anti-oxidant, anti-inflammatory and pro-angiogenic. Three of the herbs were prepared as topical patches with an enhancer and used to treat three common ailments in pilot clinical trials, viz., plantar fasciitis, undisplaced metatarsal fracture and tendonitis of the wrist (de-Quervain's disease) and the elbow (Tennis elbow). The clinical results of the pilot studies were very positive. It is therefore concluded that further explorations are justified to create medicinal herb patches of even greater efficacy. PMID- 26903863 TI - Habituation in the Tail Withdrawal Reflex Circuit is Impaired During Aging in Aplysia californica. AB - The relevance of putative contributors to age-related memory loss are poorly understood. The tail withdrawal circuit of the sea hare, a straightforward neural model, was used to investigate the aging characteristics of rudimentary learning. The simplicity of this neuronal circuit permits attribution of declines in the function of specific neurons to aging declines. Memory was impaired in advanced age animals compared to their performance at the peak of sexual maturity, with habituation training failing to attenuate the tail withdrawal response or to reduce tail motoneuron excitability, as occurred in peak maturity siblings. Baseline motoneuron excitability of aged animals was significantly lower, perhaps contributing to a smaller scope for attenuation. Conduction velocity in afferent fibers to tail sensory neurons (SN) decreased during aging. The findings suggest that age-related changes in tail sensory and motor neurons result in deterioration of a simple form of learning in Aplysia. PMID- 26903866 TI - Editorial: Recent Advances in Voltage-Gated Sodium Channels, their Pharmacology and Related Diseases. PMID- 26903865 TI - Different Contribution of Redox-Sensitive Transient Receptor Potential Channels to Acetaminophen-Induced Death of Human Hepatoma Cell Line. AB - Acetaminophen (APAP) is a safe analgesic antipyretic drug at prescribed doses. Its overdose, however, can cause life-threatening liver damage. Though, involvement of oxidative stress is widely acknowledged in APAP-induced hepatocellular death, the mechanism of this increased oxidative stress and the associated alterations in Ca(2+) homeostasis are still unclear. Among members of transient receptor potential (TRP) channels activated in response to oxidative stress, we here identify that redox-sensitive TRPV1, TRPC1, TRPM2, and TRPM7 channels underlie Ca(2+) entry and downstream cellular damages induced by APAP in human hepatoma (HepG2) cells. Our data indicate that APAP treatment of HepG2 cells resulted in increased reactive oxygen species (ROS) production, glutathione (GSH) depletion, and Ca(2+) entry leading to increased apoptotic cell death. These responses were significantly suppressed by pretreatment with the ROS scavengers N-acetyl-L-cysteine (NAC) and 4,5-dihydroxy-1,3-benzene disulfonic acid disodium salt monohydrate (Tiron), and also by preincubation of cells with the glutathione inducer Dimethylfumarate (DMF). TRP subtype-targeted pharmacological blockers and siRNAs strategy revealed that suppression of either TRPV1, TRPC1, TRPM2, or TRPM7 reduced APAP-induced ROS formation, Ca(2+) influx, and cell death; the effects of suppression of TRPV1 or TRPC1, known to be activated by oxidative cysteine modifications, were stronger than those of TRPM2 or TRPM7. Interestingly, TRPV1 and TRPC1 were labeled by the cysteine-selective modification reagent, 5,5'-dithiobis (2-nitrobenzoic acid)-2biotin (DTNB-2Bio), and this was attenuated by pretreatment with APAP, suggesting that APAP and/or its oxidized metabolites act directly on the modification target cysteine residues of TRPV1 and TRPC1 proteins. In human liver tissue, TRPV1, TRPC1, TRPM2, and TRPM7 channels transcripts were localized mainly to hepatocytes and Kupffer cells. Our findings strongly suggest that APAP-induced Ca(2+) entry and subsequent hepatocellular death are regulated by multiple redox-activated cation channels, among which TRPV1 and TRPC1 play a prominent role. PMID- 26903867 TI - Growth of Global Health Spending Share in Low and Middle Income Countries. PMID- 26903871 TI - Corrigendum: Editorial: Serotonin and Memory. AB - [This corrects the article DOI: 10.3389/fphar.2016.00008.]. PMID- 26903870 TI - Cellular Cholesterol Distribution Influences Proteolytic Release of the LRP-1 Ectodomain. AB - Low-density lipoprotein receptor-related protein-1 (LRP-1) is a multifunctional matricellular receptor composed of a large ligand-binding subunit (515-kDa alpha chain) associated with a short trans-membrane subunit (85-kDa beta-chain). LRP-1, which exhibits both endocytosis and cell signaling properties, plays a key role in tumor invasion by regulating the activity of proteinases such as matrix metalloproteinases (MMPs). LRP-1 is shed at the cell surface by proteinases such as membrane-type 1 MMP (MT1-MMP) and a disintegrin and metalloproteinase-12 (ADAM 12). Here, we show by using biophysical, biochemical, and cellular imaging approaches that efficient extraction of cell cholesterol and increased LRP-1 shedding occur in MDA-MB-231 breast cancer cells but not in MDA-MB-435 cells. Our data show that cholesterol is differently distributed in both cell lines; predominantly intracellularly for MDA-MB-231 cells and at the plasma membrane for MDA-MB-435 cells. This study highlights the relationship between the rate and cellular distribution of cholesterol and its impact on LRP-1 shedding modulation. Altogether, our data strongly suggest that the increase of LRP-1 shedding upon cholesterol depletion induces a higher accessibility of the sheddase substrate, i.e., LRP-1, at the cell surface rather than an increase of expression of the enzyme. PMID- 26903869 TI - Antioxidant Supplementation in the Treatment of Aging-Associated Diseases. AB - Oxidative stress is generally considered as the consequence of an imbalance between pro- and antioxidants species, which often results into indiscriminate and global damage at the organismal level. Elderly people are more susceptible to oxidative stress and this depends, almost in part, from a decreased performance of their endogenous antioxidant system. As many studies reported an inverse correlation between systemic levels of antioxidants and several diseases, primarily cardiovascular diseases, but also diabetes and neurological disorders, antioxidant supplementation has been foreseen as an effective preventive and therapeutic intervention for aging-associated pathologies. However, the expectations of this therapeutic approach have often been partially disappointed by clinical trials. The interplay of both endogenous and exogenous antioxidants with the systemic redox system is very complex and represents an issue that is still under debate. In this review a selection of recent clinical studies concerning antioxidants supplementation and the evaluation of their influence in aging-related diseases is analyzed. The controversial outcomes of antioxidants supplementation therapies, which might partially depend from an underestimation of the patient specific metabolic demand and genetic background, are presented. PMID- 26903872 TI - Small-Scale Fabrication of Biomimetic Structures for Periodontal Regeneration. AB - The periodontium is the supporting tissues for the tooth organ and is vulnerable to destruction, arising from overpopulating pathogenic bacteria and spirochaetes. The presence of microbes together with host responses can destroy large parts of the periodontium sometimes leading tooth loss. Permanent tissue replacements are made possible with tissue engineering techniques. However, existing periodontal biomaterials cannot promote proper tissue architectures, necessary tissue volumes within the periodontal pocket and a "water-tight" barrier, to become clinically acceptable. New kinds of small-scale engineered biomaterials, with increasing biological complexity are needed to guide proper biomimetic regeneration of periodontal tissues. So the ability to make compound structures with small modules, filled with tissue components, is a promising design strategy for simulating the anatomical complexity of the periodotium attachment complexes along the tooth root and the abutment with the tooth collar. Anatomical structures such as, intima, adventitia, and special compartments such as the epithelial cell rests of Malassez or a stellate reticulum niche need to be engineered from the start of regeneration to produce proper periodontium replacement. It is our contention that the positioning of tissue components at the origin is also necessary to promote self-organizing cell-cell connections, cell-matrix connections. This leads to accelerated, synchronized and well-formed tissue architectures and anatomies. This strategy is a highly effective preparation for tackling periodontitis, periodontium tissue resorption, and to ultimately prevent tooth loss. Furthermore, such biomimetic tissue replacements will tackle problems associated with dental implant support and perimimplantitis. PMID- 26903873 TI - Overexpression of Striated Muscle Activator of Rho Signaling (STARS) Increases C2C12 Skeletal Muscle Cell Differentiation. AB - BACKGROUND: Skeletal muscle growth and regeneration depend on the activation of satellite cells, which leads to myocyte proliferation, differentiation and fusion with existing muscle fibers. Skeletal muscle cell proliferation and differentiation are tightly coordinated by a continuum of molecular signaling pathways. The striated muscle activator of Rho signaling (STARS) is an actin binding protein that regulates the transcription of genes involved in muscle cell growth, structure and function via the stimulation of actin polymerization and activation of serum-response factor (SRF) signaling. STARS mediates cell proliferation in smooth and cardiac muscle models; however, whether STARS overexpression enhances cell proliferation and differentiation has not been investigated in skeletal muscle cells. RESULTS: We demonstrate for the first time that STARS overexpression enhances differentiation but not proliferation in C2C12 mouse skeletal muscle cells. Increased differentiation was associated with an increase in the gene levels of the myogenic differentiation markers Ckm, Ckmt2 and Myh4, the differentiation factor Igf2 and the myogenic regulatory factors (MRFs) Myf5 and Myf6. Exposing C2C12 cells to CCG-1423, a pharmacological inhibitor of SRF preventing the nuclear translocation of its co-factor MRTF-A, had no effect on myotube differentiation rate, suggesting that STARS regulates differentiation via a MRTF-A independent mechanism. CONCLUSION: These findings position STARS as an important regulator of skeletal muscle growth and regeneration. PMID- 26903874 TI - Silencing of CYP6 and APN Genes Affects the Growth and Development of Rice Yellow Stem Borer, Scirpophaga incertulas. AB - RNAi is a powerful tool to target the insect genes involved in host-pest interactions. Key insect genes are the choice for silencing to achieve pest derived resistance where resistance genes are not available in gene pool of host plant. In this study, an attempt was made to determine the effect of dsRNA designed from two genes Cytochrome P450 derivative (CYP6) and Aminopeptidase N (APN) of rice yellow stem borer (YSB) on growth and development of insect. The bioassays involved injection of chemically synthesized 5' FAM labeled 21-nt dsRNA into rice cut stems and allowing the larvae to feed on these stems which resulted in increased mortality and observed growth and development changes in larval length and weight compared with its untreated control at 12-15 days after treatment. These results were further supported by observing the reduction in transcripts expression of these genes in treated larvae. Fluorescence detection in treated larvae also proved that dsRNA was readily taken by larvae when fed on dsRNA treated stems. These results from the present study clearly show that YSB larvae fed on dsRNA designed from Cytochrome P450 and Aminopeptidase N has detrimental effect on larval growth and development. These genes can be deployed to develop YSB resistance in rice using RNAi approach. PMID- 26903868 TI - The Trafficking of the Water Channel Aquaporin-2 in Renal Principal Cells-a Potential Target for Pharmacological Intervention in Cardiovascular Diseases. AB - Arginine-vasopressin (AVP) stimulates the redistribution of water channels, aquaporin-2 (AQP2) from intracellular vesicles into the plasma membrane of renal collecting duct principal cells. By this AVP directs 10% of the water reabsorption from the 170 L of primary urine that the human kidneys produce each day. This review discusses molecular mechanisms underlying the AVP-induced redistribution of AQP2; in particular, it provides an overview over the proteins participating in the control of its localization. Defects preventing the insertion of AQP2 into the plasma membrane cause diabetes insipidus. The disease can be acquired or inherited, and is characterized by polyuria and polydipsia. Vice versa, up-regulation of the system causing a predominant localization of AQP2 in the plasma membrane leads to excessive water retention and hyponatremia as in the syndrome of inappropriate antidiuretic hormone secretion (SIADH), late stage heart failure or liver cirrhosis. This article briefly summarizes the currently available pharmacotherapies for the treatment of such water balance disorders, and discusses the value of newly identified mechanisms controlling AQP2 for developing novel pharmacological strategies. Innovative concepts for the therapy of water balance disorders are required as there is a medical need due to the lack of causal treatments. PMID- 26903875 TI - Mesenchymal Stem Cell-Derived Extracellular Vesicles Promote Angiogenesis: Potencial Clinical Application. AB - Mesenchymal stem cells (MSCs) are adult multipotent stem cells that are able to differentiate into multiple specialized cell types including osteocytes, adipocytes, and chondrocytes. MSCs exert different functions in the body and have recently been predicted to have a major clinical/therapeutic potential. However, the mechanisms of self-renewal and tissue regeneration are not completely understood. It has been shown that the biological effect depends mainly on its paracrine action. Furthermore, it has been reported that the secretion of soluble factors and the release of extracellular vesicles, such as exosomes, could mediate the cellular communication to induce cell-differentiation/self-renewal. This review provides an overview of MSC-derived exosomes in promoting angiogenicity and of the clinical relevance in a therapeutic approach. PMID- 26903876 TI - Scanning Electrochemical Microscopy Imaging during Respiratory Burst in Human Cell. AB - Phagocytic cells, such as neutrophils and monocytes, consume oxygen and generate reactive oxygen species (ROS) in response to external stimuli. Among the various ROS, the superoxide anion radical is known to be primarily produced by nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase. In the current study, we attempt to evaluate the respiratory burst by monitoring the rapid consumption of oxygen by using scanning electrochemical microscopy (SECM) imaging. The respiratory burst was measured in a human monocytic cell line (THP-1 cells) derived from an acute monocytic leukemia patient under the effect of the exogenous addition of phorbol 12-myristate 13-acetate, which acts as a differentiation inducer. SECM imaging composed of a microelectrode was used to compare oxygen consumption between normal cellular respiration and during respiratory burst in THP-1 cells. Two-dimensional respiratory activity imaging was performed using XY-scan. In addition, the quantitative evaluation of oxygen consumption in THP-1 cells was performed using a Z-scan. The results obtained show higher consumption of oxygen in cells undergoing respiratory burst. SECM imaging is thus claimed to be a highly sensitive and appropriate technique compared to other existing techniques available for evaluating oxidative stress in human cells, making it potentially useful for widespread applications in biomedical research and clinical trials. PMID- 26903877 TI - Protein Phosphorylation and Redox Modification in Stomatal Guard Cells. AB - Post-translational modification (PTM) is recognized as a major process accounting for protein structural variation, functional diversity, and the dynamics and complexity of the proteome. Since PTMs can change the structure and function of proteins, they are essential to coordinate signaling networks and to regulate important physiological processes in eukaryotes. Plants are constantly challenged by both biotic and abiotic stresses that reduce productivity, causing economic losses in crops. The plant responses involve complex physiological, cellular, and molecular processes, with stomatal movement as one of the earliest responses. In order to activate such a rapid response, stomatal guard cells employ cellular PTMs of key protein players in the signaling pathways to regulate the opening and closure of the stomatal pores. Here we discuss two major types of PTMs, protein phosphorylation and redox modification that play essential roles in stomatal movement under stress conditions. We present an overview of PTMs that occur in stomatal guard cells, especially the methods and technologies, and their applications in PTM identification and quantification. Our focus is on PTMs that modify molecular components in guard cell signaling at the stages of signal perception, second messenger production, as well as downstream signaling events and output. Improved understanding of guard cell signaling will enable generation of crops with enhanced stress tolerance, and increased yield and bioenergy through biotechnology and molecular breeding. PMID- 26903878 TI - Placental Adaptation: What Can We Learn from Birthweight:Placental Weight Ratio? AB - Appropriate fetal growth relies upon adequate placental nutrient transfer. Birthweight:placental weight ratio (BW:PW ratio) is often used as a proxy for placental efficiency, defined as the grams of fetus produced per gram placenta. An elevated BW:PW ratio in an appropriately grown fetus (small placenta) is assumed to be due to up-regulated placental nutrient transfer capacity i.e., a higher nutrient net flux per gram placenta. In fetal growth restriction (FGR), where a fetus fails to achieve its genetically pre-determined growth potential, placental weight and BW:PW ratio are often reduced which may indicate a placenta that fails to adapt its nutrient transfer capacity to compensate for its small size. This review considers the literature on BW:PW ratio in both large cohort studies of normal pregnancies and those studies offering insight into the relationship between BW:PW ratio and outcome measures including stillbirth, FGR, and subsequent postnatal consequences. The core of this review is the question of whether BW:PW ratio is truly indicative of altered placental efficiency, and whether changes in BW:PW ratio reflect those placentas which adapt their nutrient transfer according to their size. We consider this question using data from mice and humans, focusing upon studies that have measured the activity of the well characterized placental system A amino acid transporter, both in uncomplicated pregnancies and in FGR. Evidence suggests that BW:PW ratio is reduced both in FGR and in pregnancies resulting in a small for gestational age (SGA, birthweight < 10th centile) infant but this effect is more pronounced earlier in gestation (<28 weeks). In mice, there is a clear association between increased BW:PW ratio and increased placental system A activity. Additionally, there is good evidence in wild-type mice that small placentas upregulate placental nutrient transfer to prevent fetal undergrowth. In humans, this association between BW:PW ratio and placental system A activity is less clear and is worthy of further consideration, both in terms of system A and other placental nutrient transfer processes. This knowledge would help decide the value of measuring BW:PW ratio in terms of determining the risk of poor health outcomes, both in the neonatal period and long term. PMID- 26903879 TI - Influencing Factors of Thermogenic Adipose Tissue Activity. AB - Obesity is an escalating public health challenge and contributes tremendously to the disease burden globally. New therapeutic strategies are required to alleviate the health impact of obesity-related metabolic dysfunction. Brown adipose tissue (BAT) is specialized for dissipating chemical energy for thermogenesis as a defense against cold environment. Intriguingly, the brown-fat like adipocytes that dispersed throughout white adipose tissue (WAT) in rodents and humans, called "brite" or "beige" adipocytes, share similar thermogenic characteristics to brown adipocytes. Recently, researchers have focused on cognition of these thermogenic adipose tissues. Some factors have been identified to regulate the development and function of thermogenic adipose tissues. Cold exposure, pharmacological conditions, and lifestyle can enhance non-shivering thermogenesis and metabolism via some mechanisms. However, environmental pollutants, such as ambient fine particulates and ozone, may impair the function of these thermogenic adipose tissues and thereby induce metabolic dysfunction. In this review, the origin, function and influencing factors of thermogenic adipose tissues were summarized and it will provide insights into identifying new therapeutic strategies for the treatment of obesity and obesity-related diseases. PMID- 26903880 TI - Structural Features of Ion Transport and Allosteric Regulation in Sodium-Calcium Exchanger (NCX) Proteins. AB - Na(+)/Ca(2+) exchanger (NCX) proteins extrude Ca(2+) from the cell to maintain cellular homeostasis. Since NCX proteins contribute to numerous physiological and pathophysiological events, their pharmacological targeting has been desired for a long time. This intervention remains challenging owing to our poor understanding of the underlying structure-dynamic mechanisms. Recent structural studies have shed light on the structure-function relationships underlying the ion-transport and allosteric regulation of NCX. The crystal structure of an archaeal NCX (NCX_Mj) along with molecular dynamics simulations and ion flux analyses, have assigned the ion binding sites for 3Na(+) and 1Ca(2+), which are being transported in separate steps. In contrast with NCX_Mj, eukaryotic NCXs contain the regulatory Ca(2+)-binding domains, CBD1 and CBD2, which affect the membrane embedded ion-transport domains over a distance of ~80 A. The Ca(2+)-dependent regulation is ortholog, isoform, and splice-variant dependent to meet physiological requirements, exhibiting either a positive, negative, or no response to regulatory Ca(2+). The crystal structures of the two-domain (CBD12) tandem have revealed a common mechanism involving a Ca(2+)-driven tethering of CBDs in diverse NCX variants. However, dissociation kinetics of occluded Ca(2+) (entrapped at the two-domain interface) depends on the alternative-splicing segment (at CBD2), thereby representing splicing-dependent dynamic coupling of CBDs. The HDX-MS, SAXS, NMR, FRET, equilibrium (45)Ca(2+) binding and stopped flow techniques provided insights into the dynamic mechanisms of CBDs. Ca(2+) binding to CBD1 results in a population shift, where more constraint conformational states become highly populated without global conformational changes in the alignment of CBDs. This mechanism is common among NCXs. Recent HDX MS studies have demonstrated that the apo CBD1 and CBD2 are stabilized by interacting with each other, while Ca(2+) binding to CBD1 rigidifies local backbone segments of CBD2, but not of CBD1. The extent and strength of Ca(2+) dependent rigidification at CBD2 is splice-variant dependent, showing clear correlations with phenotypes of matching NCX variants. Therefore, diverse NCX variants share a common mechanism for the initial decoding of the regulatory signal upon Ca(2+) binding at the interface of CBDs, whereas the allosteric message is shaped by CBD2, the dynamic features of which are dictated by the splicing segment. PMID- 26903881 TI - Insulin-Related Peptide 5 is Involved in Regulating Embryo Development and Biochemical Composition in Pea Aphid with Wing Polyphenism. AB - In aphids there is a fecundity-dispersal trade-off between wingless and winged morphs. Recent research on the molecular mechanism of wing morphs associated with dispersal reveals that insulin receptors in the insulin signaling (IS) pathway regulate alternation of wing morphs in planthoppers. However, little is known about whether genes in the IS pathway are involved in developmental regulation in aphid nymphs with different wing morphs. In this study, we show that expression of the insulin-related peptide 5 gene (Apirp5) affects biochemical composition and embryo development of wingless pea aphids, Acyrthosiphon pisum. After comparing expression levels of major genes in the IS pathway between third instar winged and wingless nymphs, we found that Apirp5 showed higher expression in head and thorax in the wingless nymphs than in the winged nymphs. Although microinjection treatment affects physical performance in aphids, nymphs with RNA interference of Apirp5 had less weight, smaller embryos, and higher carbohydrate and protein contents compared to the control group. Comparison between winged and wingless nymphs showed a similar trend. These results indicate that Apirp5 is involved in embryo development and metabolic regulation in wing dimorphic pea aphid. PMID- 26903882 TI - Exercise Decreases Lipogenic Gene Expression in Adipose Tissue and Alters Adipocyte Cellularity during Weight Regain After Weight Loss. AB - Exercise is a potent strategy to facilitate long-term weight maintenance. In addition to increasing energy expenditure and reducing appetite, exercise also favors the oxidation of dietary fat, which likely helps prevent weight re-gain. It is unclear whether this exercise-induced metabolic shift is due to changes in energy balance, or whether exercise imparts additional adaptations in the periphery that limit the storage and favor the oxidation of dietary fat. To answer this question, adipose tissue lipid metabolism and related gene expression were studied in obese rats following weight loss and during the first day of relapse to obesity. Mature, obese rats were weight-reduced for 2 weeks with or without daily treadmill exercise (EX). Rats were weight maintained for 6 weeks, followed by relapse on: (a) ad libitum low fat diet (LFD), (b) ad libitum LFD plus EX, or (c) a provision of LFD to match the positive energy imbalance of exercised, relapsing animals. 24 h retention of dietary- and de novo-derived fat were assessed directly using (14)C palmitate/oleate and (3)H20, respectively. Exercise decreased the size, but increased the number of adipocytes in both retroperitoneal (RP) and subcutaneous (SC) adipose depots, and prevented the relapse-induced increase in adipocyte size. Further, exercise decreased the expression of genes involved in lipid uptake (CD36 and LPL), de novo lipogenesis (FAS, ACC1), and triacylglycerol synthesis (MGAT and DGAT) in RP adipose during relapse following weight loss. This was consistent with the metabolic data, whereby exercise reduced retention of de novo-derived fat even when controlling for the positive energy imbalance. The decreased trafficking of dietary fat to adipose tissue with exercise was explained by reduced energy intake which attenuated energy imbalance during refeeding. Despite having decreased expression of lipogenic genes, the net retention of de novo-derived lipid was higher in both the RP and SC adipose of exercising animals compared to their energy gap-matched controls. Our interpretation of this data is that much of this lipid is being made by the liver and subsequently trafficked to adipose tissue storage. Together, these concerted effects may explain the beneficial effects of exercise on preventing weight regain following weight loss. PMID- 26903883 TI - The Quantitative Criteria Based on the Fractal Dimensions, Entropy, and Lacunarity for the Spatial Distribution of Cancer Cell Nuclei Enable Identification of Low or High Aggressive Prostate Carcinomas. AB - BACKGROUND: Tumor grading, PSA concentration, and stage determine a risk of prostate cancer patients with accuracy of about 70%. An approach based on the fractal geometrical model was proposed to eliminate subjectivity from the evaluation of tumor aggressiveness and to improve the prediction. This study was undertaken to validate classes of equivalence for the spatial distribution of cancer cell nuclei in a larger, independent set of prostate carcinomas. METHODS: The global fractal capacity D 0, information D 1 and correlation D 2 dimension, the local fractal dimension (LFD) and the local connected fractal dimension (LCFD), Shannon entropy H and lacunarity lambda were measured using computer algorithms in digitalized images of both the reference set (n = 60) and the test set (n = 208) of prostate carcinomas. RESULTS: Prostate carcinomas were re stratified into seven classes of equivalence. The cut-off D 0-values 1.5450, 1.5820, 1.6270, 1.6490, 1.6980, 1.7640 defined the classes from C1 to C7, respectively. The other measures but the D 1 failed to define the same classes of equivalence. The pairs (D 0, LFD), (D 0, H), (D 0, lambda), (D 1, LFD), (D 1, H), (D 1, lambda) characterized the spatial distribution of cancer cell nuclei in each class. The co-application of those measures enabled the subordination of prostate carcinomas to one out of three clusters associated with different tumor aggressiveness. For D 0 < 1.5820, LFD < 1.3, LCFD > 1.5, H < 0.7, and lambda > 0.8, the class C1 or C2 contains low complexity low aggressive carcinomas exclusively. For D 0 > 1.6980, LFD > 1.7644, LCFD > 1.7051, H > 0.9, and lambda < 0.7, the class C6 or C7 contains high complexity high aggressive carcinomas. CONCLUSIONS: The cut-off D 0-values defining the classes of equivalence were validated in this study. The cluster analysis suggested that the number of the subjective Gleason grades and the number of the objective classes of equivalence could be decreased from seven to three without a loss of clinically relevant information. Two novel quantitative criteria based on the complexity and the diversity measures enabled the identification of low or high aggressive prostate carcinomas and should be verified in the future multicenter, randomized studies. PMID- 26903884 TI - Cardiorespiratory Coordination after Training and Detraining. A Principal Component Analysis Approach. AB - Our purpose was to study the effects of different training modalities and detraining on cardiorespiratory coordination (CRC). Thirty-two young males were randomly assigned to four training groups: aerobic (AT), resistance (RT), aerobic plus resistance (AT + RT), and control (C). They were assessed before training, after training (6 weeks) and after detraining (3 weeks) by means of a graded maximal test. A principal component (PC) analysis of selected cardiovascular and cardiorespiratory variables was performed to evaluate CRC. The first PC (PC1) coefficient of congruence in the three conditions (before training, after training and after detraining) was compared between groups. Two PCs were identified in 81% of participants before the training period. After this period the number of PCs and the projection of the selected variables onto them changed only in the groups subject to a training programme. The PC1 coefficient of congruence was significantly lower in the training groups compared with the C group [H (3, N=32) = 11.28; p = 0.01]. In conclusion, training produced changes in CRC, reflected by the change in the number of PCs and the congruence values of PC1. These changes may be more sensitive than the usually explored cardiorespiratory reserve, and they probably precede it. PMID- 26903886 TI - Hippocampal Non-Theta-Contingent Eyeblink Classical Conditioning: A Model System for Neurobiological Dysfunction. AB - Typical information processing is thought to depend on the integrity of neurobiological oscillations that may underlie coordination and timing of cells and assemblies within and between structures. The 3-7 Hz bandwidth of hippocampal theta rhythm is associated with cognitive processes essential to learning and depends on the integrity of cholinergic, GABAergic, and glutamatergic forebrain systems. Since several significant psychiatric disorders appear to result from dysfunction of medial temporal lobe (MTL) neurochemical systems, preclinical studies on animal models may be an important step in defining and treating such syndromes. Many studies have shown that the amount of hippocampal theta in the rabbit strongly predicts the acquisition rate of classical eyeblink conditioning and that impairment of this system substantially slows the rate of learning and attainment of asymptotic performance. Our lab has developed a brain-computer interface that makes eyeblink training trials contingent upon the explicit presence or absence of hippocampal theta. The behavioral benefit of theta contingent training has been demonstrated in both delay and trace forms of the paradigm with a two- to fourfold increase in learning speed over non-theta states. The non-theta behavioral impairment is accompanied by disruption of the amplitude and synchrony of hippocampal local field potentials, multiple-unit excitation, and single-unit response patterns dependent on theta state. Our findings indicate a significant electrophysiological and behavioral impact of the pretrial state of the hippocampus that suggests an important role for this MTL system in associative learning and a significant deleterious impact in the absence of theta. Here, we focus on the impairments in the non-theta state, integrate them into current models of psychiatric disorders, and suggest how improvement in our understanding of neurobiological oscillations is critical for theories and treatment of psychiatric pathology. PMID- 26903885 TI - Sex Differences in Behavioral Dyscontrol: Role in Drug Addiction and Novel Treatments. AB - The purpose of this review is to discuss recent findings related to sex differences in behavioral dyscontrol that lead to drug addiction, and clinical implications for humans are discussed. This review includes research conducted in animals and humans that reveals fundamental aspects of behavioral dyscontrol. The importance of sex differences in aspects of behavioral dyscontrol, such as impulsivity and compulsivity, is discussed as major determinants of drug addiction. Behavioral dyscontrol during adolescence is also an important consideration, as this is the time of onset for drug addiction. These vulnerability factors additively increase drug-abuse vulnerability, and they are integral aspects of addiction that covary and interact with sex differences. Sex differences in treatments for drug addiction are also reviewed in terms of their ability to modify the behavioral dyscontrol that underlies addictive behavior. Customized treatments to reduce behavioral dyscontrol are discussed, such as (1) using natural consequences such as non-drug rewards (e.g., exercise) to maintain abstinence, or using punishment as a consequence for drug use, (2) targeting factors that underlie behavioral dyscontrol, such as impulsivity or anxiety, by repurposing medications to relieve these underlying conditions, and (3) combining two or more novel behavioral or pharmacological treatments to produce additive reductions in drug seeking. Recent published work has indicated that factors contributing to behavioral dyscontrol are an important target for advancing our knowledge on the etiology of drug abuse, intervening with the drug addiction process and developing novel treatments. PMID- 26903888 TI - Desensitizing Addiction: Using Eye Movements to Reduce the Intensity of Substance Related Mental Imagery and Craving. AB - Eye movement desensitization and reprocessing (EMDR) is an effective treatment for posttraumatic stress disorder. During this treatment, patients recall traumatic memories while making horizontal eye movements (EM). Studies have shown that EM not only desensitize negative memories but also positive memories and imagined events. Substance use behavior and craving are maintained by maladaptive memory associations and visual imagery. Preliminary findings have indicated that these mental images can be desensitized by EMDR techniques. We conducted two proof-of-principle studies to investigate whether EM can reduce the sensory richness of substance-related mental representations and accompanying craving levels. We investigated the effects of EM on (1) vividness of food-related mental imagery and food craving in dieting and non-dieting students and (2) vividness of recent smoking-related memories and cigarette craving in daily smokers. In both experiments, participants recalled the images while making EM or keeping eyes stationary. Image vividness and emotionality, image-specific craving and general craving were measured before and after the intervention. As a behavioral outcome measure, participants in study 1 were offered a snack choice at the end of the experiment. Results of both experiments showed that image vividness and craving increased in the control condition but remained stable or decreased after the EM intervention. EM additionally reduced image emotionality (experiment 2) and affected behavior (experiment 1): participants in the EM condition were more inclined to choose healthy over unhealthy snack options. In conclusion, these data suggest that EM can be used to reduce intensity of substance-related imagery and craving. Although long-term effects are yet to be demonstrated, the current studies suggest that EM might be a useful technique in addiction treatment. PMID- 26903889 TI - An Evaluation of Universal Grammar and the Phonological Mind. AB - This paper argues against the hypothesis of a "phonological mind" advanced by Berent. It establishes that there is no evidence that phonology is innate and that, in fact, the simplest hypothesis seems to be that phonology is learned like other human abilities. Moreover, the paper fleshes out the original claim of Philip Lieberman that Universal Grammar predicts that not everyone should be able to learn every language, i.e., the opposite of what UG is normally thought to predict. The paper also underscores the problem that the absence of recursion in Piraha represents for Universal Grammar proposals. PMID- 26903890 TI - The Gradience of Multilingualism in Typical and Impaired Language Development: Positioning Bilectalism within Comparative Bilingualism. AB - A multitude of factors characterizes bi- and multilingual compared to monolingual language acquisition. Two of the most prominent viewpoints have recently been put in perspective and enriched by a third (Tsimpli, 2014): age of onset of children's exposure to their native languages, the role of the input they receive, and the timing in monolingual first language development of the phenomena examined in bi- and multilingual children's performance. This article picks up a fourth potential factor (Grohmann, 2014b): language proximity, that is, the closeness between the two or more grammars a multilingual child acquires. It is a first attempt to flesh out the proposed gradient scale of multilingualism within the approach dubbed "comparative bilingualism." The empirical part of this project comes from three types of research: (i) the acquisition and subsequent development of pronominal object clitic placement in two closely related varieties of Greek by bilectal, binational, bilingual, and multilingual children; (ii) the performance on executive control tasks by monolingual, bilectal, and bi- or multilingual children; and (iii) the role of comparative bilingualism in children with a developmental language impairment for both the diagnosis and subsequent treatment as well as the possible avoidance or weakening of how language impairment presents. PMID- 26903891 TI - Biological Agency: Its Subjective Foundations and a Large-Scale Taxonomy. AB - We will outline a theory of agency cast in theoretical psychology, viewed as a branch of a non-eliminativist biology. Our proposal will be based on an evolutionary view of the nature and functioning of the mind(s), reconsidered in a radically subjectivist, radically constructivist framework. We will argue that the activities of control systems should be studied in terms of interaction. Specifically, what an agent does belongs to the coupling of its internal dynamics with the dynamics of the external world. The internal dynamics, rooted in the species' phylogenetic history as well as in the individual's ontogenetic path, (a) determine which external dynamics are relevant to the organism, that is, they create the subjective ontology that the organism senses in the external world, and (b) determine what types of activities and actions the agent is able to conceive of and to adopt in the current situation. The external dynamics that the organism senses thus constitute its subjective environment. This notion of coupling is basically suitable for whichever organism one may want to consider. However, remarkable differences exist between the ways in which coupling may be realized, that is, between different natures and ways of functioning of control systems. We will describe agency at different phylogenetic levels: at the very least, it is necessary to discriminate between non-Intentional species, Intentional species, and a subtype of the latter called meta-Intentional. We will claim that agency can only be understood in a radically subjectivist perspective, which in turn is best grounded in a view of the mind as consciousness and experience. We will thus advance a radically constructivist view of agency and of several correlate notions (like meaning and ontology). PMID- 26903887 TI - Functional Evaluations of Genes Disrupted in Patients with Tourette's Disorder. AB - Tourette's disorder (TD) is a highly heritable neurodevelopmental disorder with complex genetic architecture and unclear neuropathology. Disruptions of particular genes have been identified in subsets of TD patients. However, none of the findings have been replicated, probably due to the complex and heterogeneous genetic architecture of TD that involves both common and rare variants. To understand the etiology of TD, functional analyses are required to characterize the molecular and cellular consequences caused by mutations in candidate genes. Such molecular and cellular alterations may converge into common biological pathways underlying the heterogeneous genetic etiology of TD patients. Herein, we review specific genes implicated in TD etiology, discuss the functions of these genes in the mammalian central nervous system and the corresponding behavioral anomalies exhibited in animal models, and importantly, review functional analyses that can be performed to evaluate the role(s) that the genetic disruptions might play in TD. Specifically, the functional assays include novel cell culture systems, genome editing techniques, bioinformatics approaches, transcriptomic analyses, and genetically modified animal models applied or developed to study genes associated with TD or with other neurodevelopmental and neuropsychiatric disorders. By describing methods used to study diseases with genetic architecture similar to TD, we hope to develop a systematic framework for investigating the etiology of TD and related disorders. PMID- 26903892 TI - Cognitive Model of Trust Dynamics Predicts Human Behavior within and between Two Games of Strategic Interaction with Computerized Confederate Agents. AB - When playing games of strategic interaction, such as iterated Prisoner's Dilemma and iterated Chicken Game, people exhibit specific within-game learning (e.g., learning a game's optimal outcome) as well as transfer of learning between games (e.g., a game's optimal outcome occurring at a higher proportion when played after another game). The reciprocal trust players develop during the first game is thought to mediate transfer of learning effects. Recently, a computational cognitive model using a novel trust mechanism has been shown to account for human behavior in both games, including the transfer between games. We present the results of a study in which we evaluate the model's a priori predictions of human learning and transfer in 16 different conditions. The model's predictive validity is compared against five model variants that lacked a trust mechanism. The results suggest that a trust mechanism is necessary to explain human behavior across multiple conditions, even when a human plays against a non-human agent. The addition of a trust mechanism to the other learning mechanisms within the cognitive architecture, such as sequence learning, instance-based learning, and utility learning, leads to better prediction of the empirical data. It is argued that computational cognitive modeling is a useful tool for studying trust development, calibration, and repair. PMID- 26903894 TI - A Test for the Assessment of Pragmatic Abilities and Cognitive Substrates (APACS): Normative Data and Psychometric Properties. AB - The Assessment of Pragmatic Abilities and Cognitive Substrates (APACS) test is a new tool to evaluate pragmatic abilities in clinical populations with acquired communicative deficits, ranging from schizophrenia to neurodegenerative diseases. APACS focuses on two main domains, namely discourse and non-literal language, combining traditional tasks with refined linguistic materials in Italian, in a unified framework inspired by language pragmatics. The test includes six tasks (Interview, Description, Narratives, Figurative Language 1, Humor, Figurative Language 2) and three composite scores (Pragmatic Productions, Pragmatic Comprehension, APACS Total). Psychometric properties and normative data were computed on a sample of 119 healthy participants representative of the general population. The analysis revealed acceptable internal consistency and good test retest reliability for almost every APACS task, suggesting that items are coherent and performance is consistent over time. Factor analysis supports the validity of the test, revealing two factors possibly related to different facets and substrates of the pragmatic competence. Finally, excellent match between APACS items and scores and the pragmatic constructs measured in the test was evidenced by experts' evaluation of content validity. The performance on APACS showed a general effect of demographic variables, with a negative effect of age and a positive effect of education. The norms were calculated by means of state of-the-art regression methods. Overall, APACS is a valuable tool for the assessment of pragmatic deficits in verbal communication. The short duration and easiness of administration make the test especially suitable to use in clinical settings. In presenting APACS, we also aim at promoting the inclusion of pragmatics in the assessment practice, as a relevant dimension in defining the patient's cognitive profile, given its vital role for communication and social interaction in daily life. The combined use of APACS with other neuropsychological tests could also improve our understanding of the cognitive substrates of pragmatic abilities and their breakdown. PMID- 26903893 TI - Where am I? Who am I? The Relation Between Spatial Cognition, Social Cognition and Individual Differences in the Built Environment. AB - Knowing who we are, and where we are, are two fundamental aspects of our physical and mental experience. Although the domains of spatial and social cognition are often studied independently, a few recent areas of scholarship have explored the interactions of place and self. This fits in with increasing evidence for embodied theories of cognition, where mental processes are grounded in action and perception. Who we are might be integrated with where we are, and impact how we move through space. Individuals vary in personality, navigational strategies, and numerous cognitive and social competencies. Here we review the relation between social and spatial spheres of existence in the realms of philosophical considerations, neural and psychological representations, and evolutionary context, and how we might use the built environment to suit who we are, or how it creates who we are. In particular we investigate how two spatial reference frames, egocentric and allocentric, might transcend into the social realm. We then speculate on how environments may interact with spatial cognition. Finally, we suggest how a framework encompassing spatial and social cognition might be taken in consideration by architects and urban planners. PMID- 26903896 TI - Using Decision Models to Enhance Investigations of Individual Differences in Cognitive Neuroscience. AB - There is great interest in relating individual differences in cognitive processing to activation of neural systems. The general process involves relating measures of task performance like reaction times or accuracy to brain activity to identify individual differences in neural processing. One limitation of this approach is that measures like reaction times can be affected by multiple components of processing. For instance, some individuals might have higher accuracy in a memory task because they respond more cautiously, not because they have better memory. Computational models of decision making, like the drift diffusion model and the linear ballistic accumulator model, provide a potential solution to this problem. They can be fitted to data from individual participants to disentangle the effects of the different processes driving behavior. In this sense the models can provide cleaner measures of the processes of interest, and enhance our understanding of how neural activity varies across individuals or populations. The advantages of this model-based approach to investigating individual differences in neural activity are discussed with recent examples of how this method can improve our understanding of the brain-behavior relationship. PMID- 26903898 TI - What Deters Crime? Comparing the Effectiveness of Legal, Social, and Internal Sanctions Across Countries. AB - The question of what deters crime is of both theoretical and practical interest. The present paper focuses on what factors deter minor, non-violent crimes, i.e., dishonest actions that violate the law. Much research has been devoted to testing the effectiveness of legal sanctions on crime, while newer models also include social sanctions (judgment of friends or family) and internal sanctions (feelings of guilt). Existing research suggests that both internal sanctions and, to a lesser extent, legal sanctions deter crime, but it is unclear whether this pattern is unique to Western countries or robust across cultures. We administered a survey study to participants in China, Colombia, Germany, Portugal, and USA, five countries from distinct cultural regions of the world. Participants were asked to report the likelihood of engaging in seven dishonest and illegal actions, and were asked to indicate the probability and severity of consequences for legal, friend, family, and internal sanctions. Results indicated that across countries, internal sanctions had the strongest deterrent effects on crime. The deterrent effects of legal sanctions were weaker and varied across countries. Furthermore, the deterrent effects of legal sanctions were strongest when internal sanctions were lax. Unexpectedly, social sanctions were positively related to likelihood of engaging in crime. Taken together, these results suggest that the relative strengths of legal and internal sanctions are robust across cultures and dishonest actions. PMID- 26903897 TI - On the Shallow Processing (Dis)Advantage: Grammar and Economy. AB - In the psycholinguistic literature it has been proposed that readers and listeners often adopt a "good-enough" processing strategy in which a "shallow" representation of an utterance driven by (top-down) extra-grammatical processes has a processing advantage over a "deep" (bottom-up) grammatically-driven representation of that same utterance. In the current contribution we claim, both on theoretical and experimental grounds, that this proposal is overly simplistic. Most importantly, in the domain of anaphora there is now an accumulating body of evidence showing that the anaphoric dependencies between (reflexive) pronominals and their antecedents are subject to an economy hierarchy. In this economy hierarchy, deriving anaphoric dependencies by deep-grammatical-operations requires less processing costs than doing so by shallow-extra-grammatical operations. In addition, in case of ambiguity when both a shallow and a deep derivation are available to the parser, the latter is actually preferred. This, we argue, contradicts the basic assumptions of the shallow-deep dichotomy and, hence, a rethinking of the good-enough processing framework is warranted. PMID- 26903899 TI - Designed Natural Spaces: Informal Gardens Are Perceived to Be More Restorative than Formal Gardens. AB - Experimental research shows that there are perceived and actual benefits to spending time in natural spaces compared to urban spaces, such as reduced cognitive fatigue, improved mood, and reduced stress. Whereas past research has focused primarily on distinguishing between distinct categories of spaces (i.e., nature vs. urban), less is known about variability in perceived restorative potential of environments within a particular category of outdoor spaces, such as gardens. Conceptually, gardens are often considered to be restorative spaces and to contain an abundance of natural elements, though there is great variability in how gardens are designed that might impact their restorative potential. One common practice for classifying gardens is along a spectrum ranging from "formal or geometric" to "informal or naturalistic," which often corresponds to the degree to which built or natural elements are present, respectively. In the current study, we tested whether participants use design informality as a cue to predict perceived restorative potential of different gardens. Participants viewed a set of gardens and rated each on design informality, perceived restorative potential, naturalness, and visual appeal. Participants perceived informal gardens to have greater restorative potential than formal gardens. In addition, gardens that were more visually appealing and more natural-looking were perceived to have greater restorative potential than less visually appealing and less natural gardens. These perceptions and precedents are highly relevant for the design of gardens and other similar green spaces intended to provide relief from stress and to foster cognitive restoration. PMID- 26903900 TI - The Role of Energy Visualization in Addressing Energy Use: Insights from the eViz Project. PMID- 26903895 TI - Socio-Emotional Development Following Very Preterm Birth: Pathways to Psychopathology. AB - Very preterm birth (VPT; < 32 weeks of gestation) has been associated with an increased risk to develop cognitive and socio-emotional problems, as well as with increased vulnerability to psychiatric disorder, both with childhood and adult onset. Socio-emotional impairments that have been described in VPT individuals include diminished social competence and self-esteem, emotional dysregulation, shyness and timidity. However, the etiology of socio-emotional problems in VPT samples and their underlying mechanisms are far from understood. To date, research has focused on the investigation of both biological and environmental risk factors associated with socio-emotional problems, including structural and functional alterations in brain areas involved in processing emotions and social stimuli, perinatal stress and pain and parenting strategies. Considering the complex interplay of the aforementioned variables, the review attempts to elucidate the mechanisms underlying the association between very preterm birth, socio-emotional vulnerability and psychopathology. After a comprehensive overview of the socio-emotional impairments associated with VPT birth, three main models of socio-emotional development are presented and discussed. These focus on biological vulnerability, early life adversities and parenting, respectively. To conclude, a developmental framework is used to consider different pathways linking VPT birth to psychopathology, taking into account the interaction between medical, biological, and psychosocial factors. PMID- 26903901 TI - The Impact of Social Pressure and Monetary Incentive on Cognitive Control. AB - We compare the effects of two prominent organizational control mechanisms-social pressure and monetary incentive-on cognitive control. Cognitive control underlies the human ability to regulate thoughts and actions in the pursuit of behavioral goals. Previous studies show that monetary incentives can contribute to goal oriented behavior by activating proactive control. There is, however, much less evidence of how social pressure affects cognitive control and task performance. In a within-subject experimental design, we tested 47 subjects performing the AX CPT task to compare the activation of cognitive control modes under social pressure and monetary incentive beyond mere instructions to perform better. Our results indicate that instructing participants to improve their performance on its own leads to a significant shift from a reactive to a proactive control mode and that both social pressure and monetary incentive further enhance performance. PMID- 26903902 TI - Numerical Activities and Information Learned at Home Link to the Exact Numeracy Skills in 5-6 Years-Old Children. AB - It is currently accepted that certain activities within the family environment contribute to develop early numerical skills before schooling. However, it is unknown whether this early experience influences both the exact and the approximate representation of numbers, and if so, which is more important for numerical tasks. In the present study the mathematical performance of 110 children (mean age 5 years 11 months) was evaluated using a battery that included tests of approximate and exact numerical abilities, as well as everyday numerical problems. Moreover, children were assessed on their knowledge of number information learned at home. The parents of the participants provided information regarding daily activities of the children and socio-demographic characteristics of the family. The results showed that the amount of numerical information learned at home was a significant predictor of participants' performance on everyday numerical problems and exact number representations, even after taking account of age, memory span and socio-economic and educational status of the family. We also found that particular activities, such as board games, correlate with the children's counting skills, which are foundational for arithmetic. Crucially, tests relying on approximate representations were not predicted by the numerical knowledge acquired at home. The present research supports claims about the importance and nature of home experiences in the child's acquisition of mathematics. PMID- 26903904 TI - Lexical Stress and Linguistic Predictability Influence Proofreading Behavior. AB - There is extensive evidence that the segmental (i.e., phonemic) layer of phonology is routinely activated during reading, but little is known about whether phonological activation extends beyond phonemes to subsegmental layers (which include articulatory information, such as voicing) and suprasegmental layers (which include prosodic information, such as lexical stress). In three proofreading experiments, we show that spelling errors are detected more reliably in syllables that are stressed than in syllables that are unstressed if comprehension is a goal of the reader, indicating that suprasegmental phonology is both active during silent reading and can influence orthographic processes. In Experiment 1, participants received instructions to read for both errors and comprehension, and we found that the effect of lexical stress interacted with linguistic predictability, such that detection of errors in more predictable words was aided by stress but detection of errors in less predictable words was not. This finding suggests that lexical stress patterns can be accessed prelexically if an upcoming word is sufficiently predictable from context. Participants with stronger vocabularies showed decreased effects of stress on task performance, which is consistent with previous findings that more skilled readers are less swayed by phonological information in decisions about orthographic form. In two subsequent experiments, participants were instructed to read only for errors (Experiment 2) or only for comprehension (Experiment 3); the effect of stress disappeared when participants read for errors and reappeared when participants read for comprehension, reconfirming our hypothesis that predictability is a driver of lexical stress effects. In all experiments, errors were detected more reliably in words that were difficult to predict from context than in words that were highly predictable. Taken together, this series of experiments contributes two important findings to the field of reading and cognition: (1) The prosodic property of lexical stress can influence orthographic processing, and (2) Predictability inhibits the detection of errors in written language processing. PMID- 26903903 TI - Verbal Semantics Drives Early Anticipatory Eye Movements during the Comprehension of Verb-Initial Sentences. AB - Studies on anticipatory processes during sentence comprehension often focus on the prediction of postverbal direct objects. In subject-initial languages (the target of most studies so far), however, the position in the sentence, the syntactic function, and the semantic role of arguments are often conflated. For example, in the sentence "The frog will eat the fly" the syntactic object ("fly") is at the same time also the last word and the patient argument of the verb. It is therefore not apparent which kind of information listeners orient to for predictive processing during sentence comprehension. A visual world eye tracking study on the verb-initial language Tagalog (Austronesian) tested what kind of information listeners use to anticipate upcoming postverbal linguistic input. The grammatical structure of Tagalog allows to test whether listeners' anticipatory gaze behavior is guided by predictions of the linear order of words, by syntactic functions (e.g., subject/object), or by semantic roles (agent/patient). Participants heard sentences of the type "Eat frog fly" or "Eat fly frog" (both meaning "The frog will eat the fly") while looking at displays containing an agent referent ("frog"), a patient referent ("fly") and a distractor. The verb carried morphological marking that allowed the order and syntactic function of agent and patient to be inferred. After having heard the verb, listeners fixated on the agent irrespective of its syntactic function or position in the sentence. While hearing the first-mentioned argument, listeners fixated on the corresponding referent in the display accordingly and then initiated saccades to the last-mentioned referent before it was encountered. The results indicate that listeners used verbal semantics to identify referents and their semantic roles early; information about word order or syntactic functions did not influence anticipatory gaze behavior directly after the verb was heard. In this verb initial language, event semantics takes early precedence during the comprehension of sentences, while arguments are anticipated temporally more local to when they are encountered. The current experiment thus helps to better understand anticipation during language processing by employing linguistic structures not available in previously studied subject-initial languages. PMID- 26903905 TI - How Early is Infants' Attention to Objects and Actions Shaped by Culture? New Evidence from 24-Month-Olds Raised in the US and China. AB - Researchers have proposed that the culture in which we are raised shapes the way that we attend to the objects and events that surround us. What remains unclear, however, is how early any such culturally-inflected differences emerge in development. Here, we address this issue directly, asking how 24-month-old infants from the US and China deploy their attention to objects and actions in dynamic scenes. By analyzing infants' eye movements while they observed dynamic scenes, the current experiment revealed striking convergences, overall, in infants' patterns of visual attention in the two communities, but also pinpointed a brief period during which their attention reliably diverged. This divergence, though modest, suggested that infants from the US devoted relatively more attention to the objects and those from China devoted relatively more attention to the actions in which they were engaged. This provides the earliest evidence for strong overlap in infants' attention to objects and events in dynamic scenes, but also raises the possibility that by 24 months, infants' attention may also be shaped subtly by the culturally-inflected attentional proclivities characteristic of adults in their cultural communities. PMID- 26903906 TI - Caregiver Training in Mindfulness-Based Positive Behavior Supports (MBPBS): Effects on Caregivers and Adults with Intellectual and Developmental Disabilities. AB - Caregivers often manage the aggressive behavior of individuals with intellectual and developmental disabilities that reside in community group homes. Sometimes this results in adverse outcomes for both the caregivers and the care recipients. We provided a 7-day intensive Mindfulness-Based Positive Behavior Support (MBPBS) training to caregivers from community group homes and assessed the outcomes in terms of caregiver variables, individuals' behaviors, and an administrative outcome. When compared to pre-MBPBS training, the MBPBS training resulted in the caregivers using significantly less physical restraints, and staff stress and staff turnover were considerably reduced. The frequency of injury to caregivers and peers caused by the individuals was significantly reduced. A benefit-cost analysis showed substantial financial savings due to staff participation in the MBPBS program. This study provides further proof-of-concept for the effectiveness of MBPBS training for caregivers, and strengthens the call for training staff in mindfulness meditation. PMID- 26903907 TI - The Take Control Course: Conceptual Rationale for the Development of a Transdiagnostic Group for Common Mental Health Problems. AB - BACKGROUND: Increasingly, research supports the utility of a transdiagnostic understanding of psychopathology. However, there is no consensus regarding the theoretical approach that best explains this. Transdiagnostic interventions can offer service delivery advantages; this is explored in the current review, focusing on group modalities and primary care settings. OBJECTIVE: This review seeks to explore whether a Perceptual Control Theory (PCT) explanation of psychopathology across disorders is a valid one. Further, this review illustrates the process of developing a novel transdiagnostic intervention (Take Control Course; TCC) from a PCT theory of functioning. METHOD: Narrative review. RESULTS AND CONCLUSIONS: Considerable evidence supports key tenets of PCT. Further, PCT offers a novel perspective regarding the mechanisms by which a number of familiar techniques, such as exposure and awareness, are effective. However, additional research is required to directly test the relative contribution of some PCT mechanisms predicted to underlie psychopathology. Directions for future research are considered. PMID- 26903909 TI - Using Caffeine Pills for Performance Enhancement. An Experimental Study on University Students' Willingness and Their Intention to Try Neuroenhancements. AB - Recent research has indicated that university students sometimes use caffeine pills for neuroenhancement (NE; non-medical use of psychoactive substances or technology to produce a subjective enhancement in psychological functioning and experience), especially during exam preparation. In our factorial survey experiment, we manipulated the evidence participants were given about the prevalence of NE amongst peers and measured the resulting effects on the psychological predictors included in the Prototype-Willingness Model of risk behavior. Two hundred and thirty-one university students were randomized to a high prevalence condition (read faked research results overstating usage of caffeine pills amongst peers by a factor of 5; 50%), low prevalence condition (half the estimated prevalence; 5%) or control condition (no information about peer prevalence). Structural equation modeling confirmed that our participants' willingness and intention to use caffeine pills in the next exam period could be explained by their past use of neuroenhancers, attitude to NE and subjective norm about use of caffeine pills whilst image of the typical user was a much less important factor. Provision of inaccurate information about prevalence reduced the predictive power of attitude with respect to willingness by 40-45%. This may be because receiving information about peer prevalence which does not fit with their perception of the social norm causes people to question their attitude. Prevalence information might exert a deterrent effect on NE via the attitude willingness association. We argue that research into NE and deterrence of associated risk behaviors should be informed by psychological theory. PMID- 26903908 TI - Development of Visual Motion Perception for Prospective Control: Brain and Behavioral Studies in Infants. AB - During infancy, smart perceptual mechanisms develop allowing infants to judge time-space motion dynamics more efficiently with age and locomotor experience. This emerging capacity may be vital to enable preparedness for upcoming events and to be able to navigate in a changing environment. Little is known about brain changes that support the development of prospective control and about processes, such as preterm birth, that may compromise it. As a function of perception of visual motion, this paper will describe behavioral and brain studies with young infants investigating the development of visual perception for prospective control. By means of the three visual motion paradigms of occlusion, looming, and optic flow, our research shows the importance of including behavioral data when studying the neural correlates of prospective control. PMID- 26903910 TI - What's in a Name? The Multiple Meanings of "Chunk" and "Chunking". PMID- 26903912 TI - Editorial: Color and Form Perception: Straddling the Boundary. PMID- 26903911 TI - Talking about Relations: Factors Influencing the Production of Relational Descriptions. AB - In a production experiment (Experiment 1) and an acceptability rating one (Experiment 2), we assessed two factors, spatial position and salience, which may influence the production of relational descriptions (such as "the ball between the man and the drawer"). In Experiment 1, speakers were asked to refer unambiguously to a target object (a ball). In Experiment 1a, we addressed the role of spatial position, more specifically if speakers mention the entity positioned leftmost in the scene as (first) relatum. The results showed a small preference to start with the left entity, which leaves room for other factors that could influence spatial reference. Thus, in the following studies, we varied salience systematically, by making one of the relatum candidates animate (Experiment 1b), and by adding attention capture cues, first subliminally by priming one relatum candidate with a flash (Experiment 1c), then explicitly by using salient colors for objects (Experiment 1d). Results indicate that spatial position played a dominant role. Entities on the left were mentioned more often as (first) relatum than those on the right (Experiments 1a-d). Animacy affected reference production in one out of three studies (in Experiment 1d). When salience was manipulated by priming visual attention or by using salient colors, there were no significant effects (Experiments 1c, d). In the acceptability rating study (Experiment 2), participants expressed their preference for specific relata, by ranking descriptions on the basis of how good they thought the descriptions fitted the scene. Results show that participants preferred most the description that had an animate entity as the first mentioned relatum. The relevance of these results for models of reference production is discussed. PMID- 26903913 TI - Intragroup Emotions: Physiological Linkage and Social Presence. AB - We investigated how technologically mediating two different components of emotion communicative expression and physiological state-to group members affects physiological linkage and self-reported feelings in a small group during video viewing. In different conditions the availability of second screen text chat (communicative expression) and visualization of group level physiological heart rates and their dyadic linkage (physiology) was varied. Within this four person group two participants formed a physically co-located dyad and the other two were individually situated in two separate rooms. We found that text chat always increased heart rate synchrony but HR visualization only with non-co-located dyads. We also found that physiological linkage was strongly connected to self reported social presence. The results encourage further exploration of the possibilities of sharing group member's physiological components of emotion by technological means to enhance mediated communication and strengthen social presence. PMID- 26903914 TI - Breakfast and Energy Drink Consumption in Secondary School Children: Breakfast Omission, in Isolation or in Combination with Frequent Energy Drink Use, is Associated with Stress, Anxiety, and Depression Cross-Sectionally, but not at 6 Month Follow-Up. AB - A considerable amount of research suggests that breakfast omission and the frequent use of caffeinated energy drinks may be associated with undesirable effects, and particularly so in children and adolescents. The current paper presents cross-sectional and longitudinal data from the Cornish Academies Project to investigate the effects of consuming energy drinks and missing breakfast on stress, anxiety, and depression in a cohort of secondary school children from the South West of England. Questionnaires were administered at two time-points (spaced 6 months apart) to collect information relating to diet and lifestyle over the previous 6 months. Demographic and school data were acquired through the School Information Management System, and single-item measures of stress, anxiety, and depression were administered at the second time-point only. Associations between breakfast and energy drink consumption and stress, anxiety, and depression were investigated, and a multivariate approach was taken so that additional variance from diet, demography, and lifestyle could be controlled for statistically. Cross-sectional analyses showed that breakfast omission was consistently associated with negative outcomes, and that this was largely observed for both those who frequently consumed energy drinks and those who did not. However, cross-lag analyses showed that neither breakfast omission or energy drink consumption, alone or in combination, was predictive of stress, anxiety, or depression at 6-month follow-up. This suggests that associations between breakfast and mental health may be bi-directional rather than breakfast being the causal factor. PMID- 26903915 TI - Modeling the Maturation of Grip Selection Planning and Action Representation: Insights from Typical and Atypical Motor Development. AB - We investigated the purported association between developmental changes in grip selection planning and improvements in an individual's capacity to represent action at an internal level [i.e., motor imagery (MI)]. Participants were groups of healthy children aged 6-7 years and 8-12 years respectively, while a group of adolescents (13-17 years) and adults (18-34 years) allowed for consideration of childhood development in the broader context of motor maturation. A group of children aged 8-12 years with probable DCD (pDCD) was included as a reference group for atypical motor development. Participants' proficiency to generate and/or engage internal action representations was inferred from performance on the hand rotation task, a well-validated measure of MI. A grip selection task designed to elicit the end-state comfort (ESC) effect provided a window into the integrity of grip selection planning. Consistent with earlier accounts, the efficiency of grip selection planning followed a non-linear developmental progression in neurotypical individuals. As expected, analysis confirmed that these developmental improvements were predicted by an increased capacity to generate and/or engage internal action representations. The profile of this association remained stable throughout the (typical) developmental spectrum. These findings are consistent with computational accounts of action planning that argue that internal action representations are associated with the expression and development of grip selection planning across typical development. However, no such association was found for our sample of children with pDCD, suggesting that individuals with atypical motor skill may adopt an alternative, sub-optimal strategy to plan their grip selection compared to their same-age control peers. PMID- 26903916 TI - Sample Size Requirements for Estimation of Item Parameters in the Multidimensional Graded Response Model. AB - Likert types of rating scales in which a respondent chooses a response from an ordered set of response options are used to measure a wide variety of psychological, educational, and medical outcome variables. The most appropriate item response theory model for analyzing and scoring these instruments when they provide scores on multiple scales is the multidimensional graded response model (MGRM) A simulation study was conducted to investigate the variables that might affect item parameter recovery for the MGRM. Data were generated based on different sample sizes, test lengths, and scale intercorrelations. Parameter estimates were obtained through the flexMIRT software. The quality of parameter recovery was assessed by the correlation between true and estimated parameters as well as bias and root-mean-square-error. Results indicated that for the vast majority of cases studied a sample size of N = 500 provided accurate parameter estimates, except for tests with 240 items when 1000 examinees were necessary to obtain accurate parameter estimates. Increasing sample size beyond N = 1000 did not increase the accuracy of MGRM parameter estimates. PMID- 26903917 TI - Evaluating Individual Students' Perceptions of Instructional Quality: An Investigation of their Factor Structure, Measurement Invariance, and Relations to Educational Outcomes. AB - Students' perceptions of instructional quality are among the most important criteria for evaluating teaching effectiveness. The present study evaluates different latent variable modeling approaches (confirmatory factor analysis, exploratory structural equation modeling, and bifactor modeling), which are used to describe these individual perceptions with respect to their factor structure, measurement invariance, and the relations to selected educational outcomes (achievement, self-concept, and motivation in mathematics). On the basis of the Programme for International Student Assessment (PISA) 2012 large-scale data sets of Australia, Canada, and the USA (N = 26,746 students), we find support for the distinction between three factors of individual students' perceptions and full measurement invariance across countries for all modeling approaches. In this regard, bifactor exploratory structural equation modeling outperformed alternative approaches with respect to model fit. Our findings reveal significant relations to the educational outcomes. This study synthesizes different modeling approaches of individual students' perceptions of instructional quality and provides insights into the nature of these perceptions from an individual differences perspective. Implications for the measurement and modeling of individually perceived instructional quality are discussed. PMID- 26903919 TI - The Relation Between Supervisors' Big Five Personality Traits and Employees' Experiences of Abusive Supervision. AB - The present study investigates the relation between supervisors' personality traits and employees' experiences of supervisory abuse, an area that - to date - remained largely unexplored in previous research. Field data collected from 103 supervisor-subordinate dyads showed that contrary to our expectations supervisors' agreeableness and neuroticism were not significantly related to abusive supervision, nor were supervisors' extraversion or openness to experience. Interestingly, however, our findings revealed a positive relation between supervisors' conscientiousness and abusive supervision. That is, supervisors high in conscientiousness were more likely to be perceived as an abusive supervisor by their employees. Overall, our findings do suggest that supervisors' Big Five personality traits explain only a limited amount of the variability in employees' experiences of abusive supervision. PMID- 26903918 TI - Infants' Understanding of Object-Directed Action: An Interdisciplinary Synthesis. AB - Recognizing that the object-directed actions of others are governed by goals and intentions is a crucial component of human interaction. These actions often occur rapidly and without explanation, yet we learn from and predict the actions of others with remarkable speed and accuracy, even during the first year of life. This review paper will serve as a bridge between several disparate literatures that, we suggest, can each contribute to our understanding of how infants interpret action. Specifically, we provide a review not just of research on infant goal attribution per se, but also incorporate findings from studies on the mirror neuron system and infant object cognition. The integration of these various research approaches allows for a novel construal of the extents and limits of early goal attribution - one in which the importance of the entire action context is considered - and points to specific future research directions. PMID- 26903921 TI - Self-Deception in Terminal Patients: Belief System at Stake. AB - A substantial minority of patients with terminal illness hold unrealistically hopeful beliefs about the severity of their disease or the nature of its treatment, considering therapy as curative rather than palliative. We propose that this attitude may be understood as self-deception, following the current psychological theories about this topic. In this article we suggest that the reason these patients deceive themselves is to preserve their belief systems. According to some philosophical accounts, the human belief system (HBS) is constituted as a web with a few stable central nodes - deep-seated beliefs - intimately related with the self. We hypothesize that the mind may possess defensive mechanisms, mostly non-conscious, that reject certain sensory inputs (e.g., a fatal diagnosis) that may undermine deep-seated beliefs. This interpretation is in line with the theory of cognitive dissonance. Following this reasoning, we also propose that HBS-related self-deception would entail a lower cognitive load than that associated with confronting the truth: whereas the latter would engage a myriad of high cognitive functions to re-configure crucial aspects of the self, including the setting of plans, goals, or even a behavioral output, the former would be mostly non-conscious. Overall, we believe that our research supports the hypothesis that in cases of terminal illness, (self )deceiving requires less effort than accepting the truth. PMID- 26903920 TI - Duration Adaptation Occurs Across the Sub- and Supra-Second Systems. AB - After repetitive exposure to a stimulus of relatively short duration, a subsequent stimulus of long duration is perceived as being even longer, and after repetitive exposure to a stimulus of relatively long duration, a subsequent stimulus of short duration is perceived as being even shorter. This phenomenon is called duration adaptation, and has been reported only for sub-second durations. We examined whether duration adaptation also occurs for supra-second durations (Experiment 1) and whether duration adaptation occurs across sub- and supra second durations (Experiment 2). Duration adaptation occurred not only for sub second durations, but also for supra-second durations and across sub- and supra second durations. These results suggest that duration adaptation involves an interval-independent system or two functionally related systems that are associated with both the sub- and supra-second durations. PMID- 26903923 TI - Commentary: Life is unfair, and so are racing sports: some athletes can randomly benefit from alerting effects due to inconsistent starting procedures. PMID- 26903922 TI - Outcome Knowledge and False Belief. AB - Virtually every social interaction involves reasoning about the perspectives of others, or 'theory of mind (ToM).' Previous research suggests that it is difficult to ignore our current knowledge when reasoning about a more naive perspective (i.e., the curse of knowledge). In this Mini Review, we discuss the implications of the curse of knowledge for certain aspects of ToM. Particularly, we examine how the curse of knowledge influences key measurements of false belief reasoning. In closing, we touch on the need to develop new measurement tools to discern the mechanisms involved in the curse of knowledge and false belief reasoning, and how they develop across the lifespan. PMID- 26903924 TI - A Social Identity Analysis of Climate Change and Environmental Attitudes and Behaviors: Insights and Opportunities. AB - Environmental challenges are often marked by an intergroup dimension. Political conservatives and progressives are divided on their beliefs about climate change, farmers come into conflict with scientists and environmentalists over water allocation or species protection, and communities oppose big business and mining companies that threaten their local environment. These intergroup tensions are reminders of the powerful influence social contexts and group memberships can have on attitudes, beliefs, and actions relating to climate change and the environment more broadly. In this paper, we use social identity theory to help describe and explain these processes. We review literature showing, how conceiving of oneself in terms of a particular social identity influences our environmental attitudes and behaviors, how relations between groups can impact on environmental outcomes, and how the content of social identities can direct group members to act in more or less pro-environmental ways. We discuss the similarities and differences between the social identity approach to these phenomena and related theories, such as cultural cognition theory, the theory of planned behavior, and value-belief-norm theory. Importantly, we also advance social-identity based strategies to foster more sustainable environmental attitudes and behaviors. Although this theoretical approach can provide important insights and potential solutions, more research is needed to build the empirical base, especially in relation to testing social identity solutions. PMID- 26903926 TI - Bebop on the Hockey Pitch: Cross-Disciplinary Creativity and Skills Transfer. AB - This paper generalizes task-specific (but dissimilar) skills, from the jazz concert stage and from the hockey field, into the domain of creativity research. What is sought are clues to what skills or creativities are transferable across dissimilar domains. It is argued that certain domain-general skills are transferable across domains, but a domain-general or 'c' creative capacity, is not. Rather than transferring some over-arching capacity to be universally creative, this research highlights factors likely to facilitate successful cross disciplinary creative expression and posits a correlation between the capacities for discriminant pattern-recognition, task-specific expertise, and sensory data collection, and the transferability of creativity. Of particular significance is the capacity for informed, selective pattern-breaking based on the 'depth' or 'insider' perspective of the domain expert; such 'expert variation and selective retention' provides creative choices and responses that are likely to be perceived by the field as creative: valuable, novel and surprising. The author is a renowned Australian studio bassist, jazz musician, and music educator who also plays field hockey for Australia at Masters level. His recently completed Ph.D. thesis, based on a performance and composition career spanning 46 years, takes the form of an analytical autoethnography drawn from personal field notes, diaries and interviews as well as published record albums. PMID- 26903925 TI - Persuading Others to Avoid Persuasion: Inoculation Theory and Resistant Health Attitudes. AB - Inoculation theory, a theory of conferring resistance to persuasive influence, has established efficacy as a messaging strategy in the health domain. In fact, the earliest research on the theory in the 1960s involved health issues to build empirical support for tenets in the inoculation framework. Over the ensuing decades, scholars have further examined the effectiveness of inoculation-based messages at creating robust positive health attitudes. We overview these efforts, highlight the structure of typical inoculation-based health messages, and describe the similarities and differences between this method of counter persuasion and other preparatory techniques commonly employed by health researchers and practitioners. Finally, we consider contexts in which inoculation oriented health messages could be most useful, and describe how the health domain could offer a useful scaffold to study conceptual issues of the theory. PMID- 26903927 TI - Consumer Behavior in Shopping Streets: The Importance of the Salesperson's Professional Personal Attention. AB - Since the early 2010s, the emergence of a new consumer has begun. In this context, consumer behavior represents one of the greatest interests of marketing scholars and business managers due to their need to adapt their companies' strategies to the new frontier. In order to advance understanding of this new consumer, this article focuses on analyzing consumer behavior in shopping streets. Thus, the aim of this research is to know what customers value in terms of salesperson-customer interaction quality nowadays. To achieve this, the authors conducted two studies. The results of the first study show that customers cite personal attention as the primary factor motivating their preference for small retailers in shopping streets. However, this motivation is not as relevant one for those who prefer malls. This result provides a point on which to research service quality incorporating personal attention in a second study. Using the SERVQUAL-P scale, the authors elaborate three lenses through which the quality of service from the customer's point of view can be analyzed: normative expectations, predictive expectations, and the importance of each attribute. The most striking result is that the dimensions of expectations (normative and predictive) are the same; these results demonstrate that customers are coherent in making assessments of their expectations, evaluating service quality and satisfaction with similar criteria. However, these dimensions are different from the dimensions of importance. Our main contribution lies in the finding that personal attention, when assessed using the scale of attribute importance, is split into two dimensions: (1) courteous attention and (2) personal relationship. Courteous attention is always welcome, but personal relationships are less valued and are often even rejected. The article concludes with a discussion of the implications of these findings for marketing practices and research. PMID- 26903928 TI - Assessment of Emotional Experience and Emotional Recognition in Complicated Grief. AB - There is substantial evidence of bias in the processing of emotion in people with complicated grief (CG). Previous studies have tended to assess the expression of emotion in CG, but other aspects of emotion (mainly emotion recognition, and the subjective aspects of emotion) have not been addressed, despite their importance for practicing clinicians. A quasi-experimental design with two matched groups (Complicated Grief, N = 24 and Non-Complicated Grief, N = 20) was carried out. The Facial Expression of Emotion Test (emotion recognition), a set of pictures from the International Affective Picture System (subjective experience of emotion) and the Symptom Checklist 90 Revised (psychopathology) were employed. The CG group showed lower scores on the dimension of valence for specific conditions on the IAPS, related to the subjective experience of emotion. In addition, they presented higher values of psychopathology. In contrast, statistically significant results were not found for the recognition of emotion. In conclusion, from a neuropsychological point of view, the subjective aspects of emotion and psychopathology seem central in explaining the experience of those with CG. These results are clinically significant for psychotherapists and psychoanalysts working in the field of grief and loss. PMID- 26903929 TI - Booze, Bars, and Bystander Behavior: People Who Consumed Alcohol Help Faster in the Presence of Others. AB - People help each other less often and less quickly when bystanders are present. In this paper, we propose that alcohol consumption could attenuate or reverse this so-called bystander effect. Alcohol impairs people cognitively and perceptually, leading them to think less about the presence of others and behave less inhibited. Moreover, alcohol makes people more prone to see the benefits of helping and not the costs. To provide an initial test of these lines of reasoning, we invited visitors of bars in Amsterdam to join our study at a secluded spot at the bar. We manipulated bystander presence, and at the end of the study, we measured alcohol consumption. When participants took their seats, the experimenter dropped some items. We measured how many items were picked up and how quickly participants engaged in helping. Results revealed that alcohol did not influence the bystander effect in terms of the amount of help given. But importantly, it did influence the bystander effect in terms of response times: people who consumed alcohol actually came to aid faster in the presence of others. PMID- 26903931 TI - The Role of Incomplete Information and Others' Choice in Reducing Traffic: A Pilot Study. AB - In this study, we investigate the role of payoff information and conformity in improving network performance in a traffic dilemma known as the Braess paradox. Our goal is to understand when decisions are guided by selfish motivations or otherwise by social ones. For this purpose, we consider the manipulation of others' choice, public and private monitoring and information on distribution of choices. Data show that when social comparison was not salient, participants were more cooperative. By contrast, cooperativeness of others' choice made participants more competitive leading to traffic and collective performance decrease. The implications of these findings to the literature on social dilemmas are discussed. PMID- 26903930 TI - Electrophysiological Correlates of Second-Language Syntactic Processes Are Related to Native and Second Language Distance Regardless of Age of Acquisition. AB - In the present study, we investigate how early and late L2 learners process L2 grammatical traits that are either present or absent in their native language (L1). Thirteen early (AoA = 4 years old) and 13 late (AoA = 18 years old) Spanish learners of Basque performed a grammatical judgment task on auditory Basque sentences while their event-related brain potentials (ERPs) were recorded. The sentences contained violations of a syntactic property specific to participants' L2, i.e., ergative case, or violations of a syntactic property present in both of the participants' languages, i.e., verb agreement. Two forms of verb agreement were tested: subject agreement, found in participants' L1 and L2, and object agreement, present only in participants' L2. Behaviorally, early bilinguals were more accurate in the judgment task than late L2 learners. Early bilinguals showed native-like ERPs for verb agreement, which differed from the late learners' ERP pattern. Nonetheless, approximation to native-likeness was greater for the subject-verb agreement processing, the type of verb-agreement present in participants' L1, compared to object-verb agreement, the type of verb-agreement present only in participants' L2. For the ergative argument alignment, unique to L2, the two non-native groups showed similar ERP patterns which did not correspond to the natives' ERP pattern. We conclude that non-native syntactic processing approximates native processing for early L2 acquisition and high proficiency levels when the syntactic property is common to the L1 and L2. However, syntactic traits that are not present in the L1 do not rely on native like processing, despite early AoA and high proficiency. PMID- 26903932 TI - Adequacy of the Sequential-Task Paradigm in Evoking Ego-Depletion and How to Improve Detection of Ego-Depleting Phenomena. PMID- 26903933 TI - Resonant Dynamics of Grounded Cognition: Explanation of Behavioral and Neuroimaging Data Using the ART Neural Network. AB - Research on grounded cognition suggests that the processing of a word or concept reactivates the perceptual representations that are associated with the referent object. The objective of this work is to demonstrate how behavioral and functional neuroimaging data on grounded cognition can be understood as different manifestations of the same cortical circuit designed to achieve stable category learning, as proposed by the adaptive resonance theory (ART). We showed that the ART neural network provides a mechanistic explanation of why reaction times in behavioral studies depend on the expectation or attentional priming created by the word meaning (Richter and Zwaan, 2009). A mismatch between top-down expectation and bottom-up sensory data activates an orienting subsystem that slows execution of the current task. Furthermore, we simulated the data from functional neuroimaging studies of color knowledge retrieval that showed anterior shift (Chao and Martin, 1999; Thompson-Schill, 2003) and an overlap effect (Simmons et al., 2007; Hsu et al., 2011) in the left fusiform gyrus. We explain the anterior effect as a result of the partial activation of different components of the same ART circuit in the condition of passive viewing. Conversely, a demanding perceptual task requires activation of the whole ART circuit. This condition is reflected in the fMRI image as an overlap between cortical activation during perceptual and conceptual processing. We conclude that the ART neural network is able to explain how the brain grounds symbols in perception via perceptual simulation. PMID- 26903934 TI - The "Smart Dining Table": Automatic Behavioral Tracking of a Meal with a Multi Touch-Computer. AB - Studying how humans eat in the context of a meal is important to understanding basic mechanisms of food intake regulation and can help develop new interventions for the promotion of healthy eating and prevention of obesity and eating disorders. While there are a number of methodologies available for behavioral evaluation of a meal, there is a need for new tools that can simplify data collection through automatic and online analysis. Also, there are currently no methods that leverage technology to add a dimension of interactivity to the meal table. In this study, we examined the feasibility of a new technology for automatic detection and classification of bites during a laboratory meal. We used a SUR40 multi-touch tabletop computer, powered by an infrared camera behind the screen. Tags were attached to three plates, allowing their positions to be tracked, and the saturation (a measure of the infrared intensity) in the surrounding region was measured. A Kinect camera was used to record the meals for manual verification and provide gesture detection for when the bites were taken. Bite detections triggered classification of the source plate by the SUR40 based on saturation flux in the preceding time window. Five healthy subjects (aged 20 40 years, one female) were tested, providing a total sample of 320 bites. Sensitivity, defined as the number of correctly detected bites out of the number of actual bites, was 67.5%. Classification accuracy, defined as the number of correctly classified bites out of those detected, was 82.4%. Due to the poor sensitivity, a second experiment was designed using a single plate and a Myo armband containing a nine-axis accelerometer as an alternative method for bite detection. The same subjects were tested (sample: 195 bites). Using a simple threshold on the pitch reading of the magnetometer, the Myo data achieved 86.1% sensitivity vs. 60.5% with the Kinect. Further, the precision of positive predictive value was 72.1% for the Myo vs. 42.8% for the Kinect. We conclude that the SUR40 + Myo combination is feasible for automatic detection and classification of bites with adequate accuracy for a range of applications. PMID- 26903935 TI - Understanding and Remediating Social-Cognitive Dysfunctions in Patients with Serious Mental Illness Using Relational Frame Theory. AB - Impairments in social cognition and perspective-taking play an important role in the psychopathology and social functioning of individuals with social anxiety, autism, or schizophrenia-spectrum disorders, among other clinical presentations. Perspective-taking has mostly been studied using the concept of Theory of Mind (ToM), which describes the sequential development of these skills in young children, as well as clinical populations experiencing perspective-taking difficulties. Several studies mention positive results of ToM based training programs; however, the precise processes involved in the achievement of these improvements are difficult to determine. Relational Frame Theory (RFT) is a modern behavioral account of complex cognitive functions, and is argued to provide a more precise approach to the assessment and training of perspective taking, among other relational skills. Results of RFT-based studies of perspective-taking in developmental and clinical settings are discussed. The development of training methods targeting perspective-taking deficits from an RFT point of view appears to provide promising applications for the enhancement of current treatments of people with social-cognitive dysfunctions. PMID- 26903936 TI - Editorial: Refining Prevention: Genetic and Epigenetic Contributions. PMID- 26903937 TI - Bang Your Head: Using Heavy Metal Music to Promote Scientific Thinking in the Classroom. PMID- 26903938 TI - Editorial: The Role of Working Memory and Executive Function in Communication under Adverse Conditions. PMID- 26903939 TI - When "He" Can Also Be "She": An ERP Study of Reflexive Pronoun Resolution in Written Mandarin Chinese. AB - The gender information in written Chinese third person pronouns is not symmetrically encoded: the character for "he" (, with semantic radical , meaning human) is used as a default referring to every individual, while the character for "she" (, with semantic radical , meaning woman) indicates females only. This critical feature could result in different patterns of processing of gender information in text, but this is an issue that has seldom been addressed in psycholinguistics. In Chinese, the written forms of the reflexive pronouns are composed of a pronoun plus the reflexive "/self" (/himself and /herself). The present study focuses on how such gender specificity interacts with the gender type of an antecedent, whether definitional (proper name) or stereotypical (stereotypical role noun) during reflexive pronoun resolution. In this event related potential (ERP) study, gender congruity between a reflexive pronoun and its antecedent was studied by manipulating the gender type of antecedents and the gender specificity of reflexive pronouns (default: /himself vs. specific: /herself). Results included a P200 "attention related" congruity effect for /himself and a P600 "integration difficulty" congruity effect for /herself. Reflexive pronoun specificity independently affected the P200 and N400 components. These results highlight the role of /himself as a default applicable to both genders and indicate that only the processing of /herself supports a two stage model for anaphor resolution. While both reflexive pronouns are evaluated at the bonding stage, the processing of the gender-specific reflexive pronoun is completed in the resolution stage. PMID- 26903940 TI - The Dorsal Anterior Cingulate Cortex Modulates Dialectical Self-Thinking. AB - Dialectical self-thinking involves holding the view that one can possess contradictory traits such as extraverted and introverted. Prior work has demonstrated that the dorsal part of anterior cingulate cortex (dACC) plays a crucial role in conflict monitoring as well as self-related processing. Here, we tested the function of dACC in dialectical self-thinking using a modified classical self-referential paradigm (self- vs. other-referential thinking), in which participants had to make a judgment whether a simultaneously presented pair of contradictory or non-contradictory traits properly described them while brain activity was recording using functional magnetic resonance imaging (fMRI). The data showed that activity in the dACC during the processing of self-relevant conflicting information was positively correlated with participants' dispositional level of naive dialecticism (measured with the Dialectical Self Scale). Psychophysiological interaction (PPI) analyses further revealed increased functional connectivity between the dACC and the caudate, middle temporal gyrus and hippocampus during the processing of self-relevant conflicting information for dialectical thinkers. These results support the hypothesis that the dACC has a key role in dialectical self-thinking. PMID- 26903941 TI - Visual Search of Mooney Faces. AB - Faces spontaneously capture attention. However, which special attributes of a face underlie this effect is unclear. To address this question, we investigate how gist information, specific visual properties and differing amounts of experience with faces affect the time required to detect a face. Three visual search experiments were conducted investigating the rapidness of human observers to detect Mooney face images. Mooney images are two-toned, ambiguous images. They were used in order to have stimuli that maintain gist information but limit low level image properties. Results from the experiments show: (1) Although upright Mooney faces were searched inefficiently, they were detected more rapidly than inverted Mooney face targets, demonstrating the important role of gist information in guiding attention toward a face. (2) Several specific Mooney face identities were searched efficiently while others were not, suggesting the involvement of specific visual properties in face detection. (3) By providing participants with unambiguous gray-scale versions of the Mooney face targets prior to the visual search task, the targets were detected significantly more efficiently, suggesting that prior experience with Mooney faces improves the ability to extract gist information for rapid face detection. However, a week of training with Mooney face categorization did not lead to even more efficient visual search of Mooney face targets. In summary, these results reveal that specific local image properties cannot account for how faces capture attention. On the other hand, gist information alone cannot account for how faces capture attention either. Prior experience facilitates the effect of gist on visual search of faces; making faces a special object category for guiding attention. PMID- 26903943 TI - Corrigendum: Social Daydreaming and Adjustment: An Experience-Sampling Study of Socio-Emotional Adaptation During a Life Transition. AB - [This corrects the article on p. 13 in vol. 7, PMID: 26834685.]. PMID- 26903942 TI - Response: Commentary: Multimodal theories of recognition and their relation to Molyneux's question. PMID- 26903944 TI - A Prospective Pilot Investigation of Brain Volume, White Matter Hyperintensities, and Hemorrhagic Lesions after Mild Traumatic Brain Injury. AB - Traumatic brain injury (TBI) is among the most common neurological disorders. Hemorrhagic lesions and white matter hyperintensities (WMH) are radiological features associated with moderate and severe TBI. Brain volume reductions have also been observed during the months following injury. In concussion, no signs of injury are observed on conventional magnetic resonance imaging (MRI), which may be a true feature of concussion or merely due to the limited sensitivity of imaging techniques used so far. Moreover, it is not known whether volume reductions are due to the resolution of trauma-related edema or a true volume loss. Forty-five collegiate-level ice hockey players (20 females) and 15 controls (9 females), 40 players underwent 3-T MRI for hemorrhages [multi-echo susceptibility-weighted imaging (SWI)], WMH (three-dimensional fluid-attenuated inversion recovery), and brain volume at the beginning and the end of the hockey season. Concussed athletes underwent additional imaging and neuropsychological testing at 3 days, 2 weeks, and 2 months after injury. At the end of the hockey season, brain volume was reduced compared to controls by 0.32% (p < 0.034) in the whole cohort and by 0.26% (p < 0.09) in the concussed athletes. Two weeks and 2 months after concussion, brain volume was reduced by -0.08% (p = 0.027) and 0.23% (p = 0.035), respectively. In athletes, the WMH were significantly closer to the interface between gray matter and white matter compared to controls. No significant changes in the number of WMH over the duration of the study were found in athletes. No microhemorrhages were detected as a result of concussion or playing a season of ice hockey. We conclude that mild TBI does not lead to transient increases in brain volume and no new microbleeds or WMH are detectable after concussion. Brain volume reductions appear by 2 weeks after concussion and persist until at least 2 months after concussion. Brain volume is reduced between the beginning and the end of the ice hockey season. PMID- 26903945 TI - Immunoablation and Stem Cell Transplantation in Amyotrophic Lateral Sclerosis: The Ultimate Test for the Autoimmune Pathogenesis Hypothesis. PMID- 26903946 TI - Feeding Problems Are Persistent in Children with Severe Congenital Hyperinsulinism. AB - BACKGROUND: Congenital hyperinsulinism (CHI) is a rare but severe disorder of hypoglycemia in children, often complicated by brain injury. In CHI, the long term prevention of hypoglycemia is dependent on reliable enteral intake of glucose. However, feeding problems (FPs) often impede oral glucose delivery, thereby complicating the management of hypoglycemia. FPs have not been systematically characterized in follow-up in a cohort with CHI. AIMS: We aimed to determine the prevalence, types, and persistence of FPs in a cohort of children with CHI and investigate potential causal factors. METHODS: FPs were defined as difficulty with sucking, swallowing, vomiting, and food refusal (or a combination) in an observational study in 83 children in a specialized CHI treatment center. The prevalence of FPs at diagnosis, 6, and 12 months after diagnosis were noted. Genetic mutation status and markers of severity of CHI were tested for association with FPs. RESULTS: A third of children with CHI had FPs (n = 28), of whom 93% required antireflux medication and 75% required nasogastric and gastrostomy tube feeding. Sucking and swallowing problems were present at diagnosis but absent later. Vomiting was present in 54% at 6 months, while food refusal was present in 68% at 6 months and 52% at 12 months. The age at commencing and stopping nasogastric tube feeding did not correlate with FPs frequency at 6 and 12 months. Children with FPs had severe hypoglycemia at diagnosis and required glucagon infusion more often [odds ratio (OR) (95% confidence intervals) (95% CI) 28.13 (2.6-300.1), p = 0.006] to normalize glucose levels. FPs were more frequent in those with diffuse CHI undergoing subtotal pancreatectomy [n (%) = 10 (35%) vs. 0 (0%), p < 0.001], in contrast to those with spontaneous resolution [6 (22%) vs. 32 (58%), p = 0.002]. Those undergoing focal lesionectomy also had reduced FPs at 6 months after diagnosis [OR (95% CI) 0.01 (0.0-0.2), R (2) = 0.42, p = 0.004]. These observations suggest that persistence of hyperinsulinism was associated with FPs. CONCLUSION: FPs occur in a significant proportion of children with CHI. Severe hyperinsulinism, rather than nasogastric tube feeding or medications, is the main factor associated with FPs. PMID- 26903947 TI - Disruption of the Suprachiasmatic Nucleus in Fibroblast Growth Factor Signaling Deficient Mice. AB - Fibroblast growth factor (Fgf) 8 is essential for the development of multiple brain regions. Previous studies from our laboratory showed that reduced Fgf8 signaling led to the developmental alterations of neuroendocrine nuclei that originated within the diencephalon, including the paraventricular (PVN) and supraoptic (SON) nuclei. To further understand the role of Fgf8 in the development of other hypothalamic nuclei, we examined if Fgf8 and its cognate receptor, Fgfr1, also impact the integrity of the suprachiasmatic nuclei (SCN). The SCN control an organism's circadian rhythm and contain vasoactive intestinal peptide (VIP)-producing neurons as the main input neurons. Mice hypomorphic for Fgf8, Fgfr1, or both were examined for their SCN volume and the number of VIP neurons on postnatal day (PN) 0; adult hypomorphic mice were further examined for SCN function by quantifying SCN neuronal activation using cFos as a marker. On PN0, mice homozygous for Fgf8 hypomorphy displayed the most severe reduction of the SCN volume and VIP neurons. Those heterozygous for Fgf8 hypomorphy alone or Fgf8 combined with Fgfr1 hypomorphy, called double heterozygotes (DH), showed normal SCN volume but significantly reduced VIP neurons, albeit less severely than the homozygotes. Adult wild type, heterozygous Fgf8 hypomorphs (F8 Het), and DH mice were also examined for SCN cFos activation at three time points: 1 h (morning), 6 h (afternoon), and 11 h (evening) after light onset. In F8 Het mice, a significant change in the pattern of cFos immunostaining that may reflect delayed morning SCN activation was observed. Overall, our studies provide evidence supporting that deficiencies in Fgf8 not only impact the structural integrity of the SCN but also the pattern of SCN activation in response to light. PMID- 26903949 TI - Exploration of Molecular Network Variations in Different Subtypes of Human Non functional Pituitary Adenomas. PMID- 26903948 TI - The Role of Dafachronic Acid Signaling in Development and Longevity in Caenorhabditis elegans: Digging Deeper Using Cutting-Edge Analytical Chemistry. AB - Steroid hormones regulate physiological processes in species ranging from plants to humans. A wide range of steroid hormones exist, and their contributions to processes, such as growth, reproduction, development, and aging, is almost always complex. Understanding the biosynthetic pathways that generate steroid hormones and the signaling pathways that mediate their effects is thus of fundamental importance. In this work, we review recent advances in (i) the biological role of steroid hormones in the roundworm Caenorhabditis elegans and (ii) the development of novel methods to facilitate the detection and identification of these molecules. Our current understanding of steroid signaling in this simple organism serves to illustrate the challenges we face moving forward. First, it seems clear that we have not yet identified all of the enzymes responsible for steroid biosynthesis and/or degradation. Second, perturbation of steroid signaling affects a wide range of phenotypes, and subtly different steroid molecules can have distinct effects. Finally, steroid hormone levels are critically important, and minute variations in quantity can profoundly impact a phenotype. Thus, it is imperative that we develop innovative analytical tools and combine them with cutting-edge approaches including comprehensive and highly selective liquid chromatography coupled to mass spectrometry based on new methods such as supercritical fluid chromatography coupled to mass spectrometry (SFC-MS) if we are to obtain a better understanding of the biological functions of steroid signaling. PMID- 26903950 TI - Editorial: Putting the "Why" Back into Bone "Archytecture". PMID- 26903951 TI - Metagenomic Analysis Suggests Modern Freshwater Microbialites Harbor a Distinct Core Microbial Community. AB - Modern microbialites are complex microbial communities that interface with abiotic factors to form carbonate-rich organosedimentary structures whose ancestors provide the earliest evidence of life. Past studies primarily on marine microbialites have inventoried diverse taxa and metabolic pathways, but it is unclear which of these are members of the microbialite community and which are introduced from adjacent environments. Here we control for these factors by sampling the surrounding water and nearby sediment, in addition to the microbialites and use a metagenomics approach to interrogate the microbial community. Our findings suggest that the Pavilion Lake microbialite community profile, metabolic potential and pathway distributions are distinct from those in the neighboring sediments and water. Based on RefSeq classification, members of the Proteobacteria (e.g., alpha and delta classes) were the dominant taxa in the microbialites, and possessed novel functional guilds associated with the metabolism of heavy metals, antibiotic resistance, primary alcohol biosynthesis and urea metabolism; the latter may help drive biomineralization. Urea metabolism within Pavilion Lake microbialites is a feature not previously associated in other microbialites. The microbialite communities were also significantly enriched for cyanobacteria and acidobacteria, which likely play an important role in biomineralization. Additional findings suggest that Pavilion Lake microbialites are under viral selection as genes associated with viral infection (e.g CRISPR-Cas, phage shock and phage excision) are abundant within the microbialite metagenomes. The morphology of Pavilion Lake microbialites changes dramatically with depth; yet, metagenomic data did not vary significantly by morphology or depth, indicating that microbialite morphology is altered by other factors, perhaps transcriptional differences or abiotic conditions. This work provides a comprehensive metagenomic perspective of the interactions and differences between microbialites and their surrounding environment, and reveals the distinct nature of these complex communities. PMID- 26903952 TI - Faustoviruses: Comparative Genomics of New Megavirales Family Members. AB - An emerging interest for the giant virus discovery process, genome sequencing and analysis has allowed an expansion of the number of known Megavirales members. Using the protist Vermamoeba sp. as cell support, a new giant virus named Faustovirus has been isolated. In this study, we describe the genome sequences of nine Faustoviruses and build a genomic comparison in order to have a comprehensive overview of genomic composition and diversity among this new virus family. The average sequence length of these viruses is 467,592.44 bp (ranging from 455,803 to 491,024 bp), making them the fourth largest Megavirales genome after Mimiviruses, Pandoraviruses, and Pithovirus sibericum. Faustovirus genomes displayed an average G+C content of 37.14 % (ranging from 36.22 to 39.59%) which is close to the G+C content range of the Asfarviridae genomes (38%). The proportion of best matches and the phylogenetic analysis suggest a shared origin with Asfarviridae without belonging to the same family. The core-gene-based phylogeny of Faustoviruses study has identified four lineages. These results were confirmed by the analysis of amino acids and COGs category distribution. The diversity of the gene composition of these lineages is mainly explained by gene deletion or acquisition and some exceptions for gene duplications. The high proportion of best matches from Bacteria and Phycodnaviridae on the pan-genome and unique genes may be explained by an interaction occurring after the separation of the lineages. The Faustovirus core-genome appears to consolidate the surrounding of 207 genes whereas the pan-genome is described as an open pan genome, its enrichment via the discovery of new Faustoviruses is required to better seize all the genomic diversity of this family. PMID- 26903953 TI - Susceptibility of Austrian Clinical Klebsiella and Enterobacter Isolates Linked to Patient-Related Data. AB - The aim of the study was to analyze the antimicrobial susceptibility of Austrian clinical Klebsiella sp. and Enterobacter sp. isolates linked to patient-related data over a time period from 1998 to 2014. The main findings of this study were (i) a marked difference of antibiotic susceptibility rates between different infection sites for both Klebsiella sp. and Enterobacter sp., (ii) significantly greater percentages of resistant isolates among both Klebsiella sp. and Enterobacter sp. in male patients compared to female patients and (iii) significantly greater percentages of resistant isolates among both Klebsiella sp. and Enterobacter sp. from hospital-derived samples compared to samples from the community. In conclusion, our statistical data analysis clearly indicated a strong association of patient-related data and Klebsiella sp. and Enterobacter sp. susceptibility profiles. PMID- 26903955 TI - Microevolution Analysis of Bacillus coahuilensis Unveils Differences in Phosphorus Acquisition Strategies and Their Regulation. AB - Bacterial genomes undergo numerous events of gene losses and gains that generate genome variability among strains of the same species (microevolution). Our aim was to compare the genomes and relevant phenotypes of three Bacillus coahuilensis strains from two oligotrophic hydrological systems in the Cuatro Cienegas Basin (Mexico), to unveil the environmental challenges that this species cope with, and the microevolutionary differences in these genotypes. Since the strains were isolated from a low P environment, we placed emphasis on the search of different phosphorus acquisition strategies. The three B. coahuilensis strains exhibited similar numbers of coding DNA sequences, of which 82% (2,893) constituted the core genome, and 18% corresponded to accessory genes. Most of the genes in this last group were associated with mobile genetic elements (MGEs) or were annotated as hypothetical proteins. Ten percent of the pangenome consisted of strain specific genes. Alignment of the three B. coahuilensis genomes indicated a high level of synteny and revealed the presence of several genomic islands. Unexpectedly, one of these islands contained genes that encode the 2-keto-3 deoxymannooctulosonic acid (Kdo) biosynthesis enzymes, a feature associated to cell walls of Gram-negative bacteria. Some microevolutionary changes were clearly associated with MGEs. Our analysis revealed inconsistencies between phenotype and genotype, which we suggest result from the impossibility to map regulatory features to genome analysis. Experimental results revealed variability in the types and numbers of auxotrophies between the strains that could not consistently be explained by in silico metabolic models. Several intraspecific differences in preferences for carbohydrate and phosphorus utilization were observed. Regarding phosphorus recycling, scavenging, and storage, variations were found between the three genomes. The three strains exhibited differences regarding alkaline phosphatase that revealed that in addition to gene gain and loss, regulation adjustment of gene expression also has contributed to the intraspecific diversity of B. coahuilensis. PMID- 26903956 TI - Eradication of Biofilm-Like Microcolony Structures of Borrelia burgdorferi by Daunomycin and Daptomycin but not Mitomycin C in Combination with Doxycycline and Cefuroxime. AB - Lyme disease, caused by Borrelia burgdorferi, is the most common vector-borne disease in the United States and Europe. While the majority of Lyme disease patients can resolve their symptoms if treated promptly, 10-20% of patients suffer from prolonged symptoms called post-treatment Lyme disease syndrome (PTLDS). Although the cause for PTLDS is unclear, one possibility is the presence of bacterial persisters not effectively cleared by the current Lyme antibiotics. Recent studies identified several drug candidates including daptomycin, daunomycin, doxorubicin, and mitomycin C that had good activity against B. burgdorferi persisters. However, their relative activities against B. burgdorferi persisters have not been evaluated under the same conditions. In this study, we tested the anti-persister activities of these drugs against both 7-day and 15-day old stationary phase cultures of B. burgdorferi individually as well as in combination with Lyme antibiotics doxycycline and cefuroxime (Ceftin). Our findings demonstrate daunomycin and daptomycin were more active than mitomycin C in single drug comparison at 10 and 20 MUM, as well as in drug combinations with doxycycline and cefuroxime. In addition, daunomycin was more active than doxorubicin which correlated with their ability to stain and accumulate in B. burgdorferi. The two drug combination of doxycycline and cefuroxime was unable to eradicate biofilm-like microcolonies of B. burgdorferi persisters. However, the addition of either daunomycin or daptomycin to the doxycycline + cefuroxime combination completely eradicated the biofilm-like structures and produced no visible bacterial regrowth after 7 and 21 days, while the addition of doxorubicin was unable to prevent regrowth at either 7 or 21 day subculture. Mitomycin C in combination with doxycycline and cefuroxime caused no regrowth at 7 days but visible spirochetal regrowth occurred after 21 day subculture. Furthermore, we found that cefuroxime (Ceftin), the third commonly used and most active antibiotic to treat Lyme disease, could replace cefoperazone (a drug no longer available in the US) in the daptomycin + doxycycline combination with complete eradication of the biofilm-like structures as shown by lack of any regrowth in subcultures. Our findings may have implications for improved treatment of Lyme disease. PMID- 26903954 TI - Porphyromonas gingivalis: An Overview of Periodontopathic Pathogen below the Gum Line. AB - Periodontal disease represents a group of oral inflammatory infections initiated by oral pathogens which exist as a complex biofilms on the tooth surface and cause destruction to tooth supporting tissues. The severity of this disease ranges from mild and reversible inflammation of the gingiva (gingivitis) to chronic destruction of connective tissues, the formation of periodontal pocket and ultimately result in loss of teeth. While human subgingival plaque harbors more than 500 bacterial species, considerable research has shown that Porphyromonas gingivalis, a Gram-negative anaerobic bacterium, is the major etiologic agent which contributes to chronic periodontitis. This black-pigmented bacterium produces a myriad of virulence factors that cause destruction to periodontal tissues either directly or indirectly by modulating the host inflammatory response. Here, this review provides an overview of P. gingivalis and how its virulence factors contribute to the pathogenesis with other microbiome consortium in oral cavity. PMID- 26903957 TI - Ketide Synthase (KS) Domain Prediction and Analysis of Iterative Type II PKS Gene in Marine Sponge-Associated Actinobacteria Producing Biosurfactants and Antimicrobial Agents. AB - The important biological macromolecules, such as lipopeptide and glycolipid biosurfactant producing marine actinobacteria were analyzed and their potential linkage between type II polyketide synthase (PKS) genes was explored. A unique feature of type II PKS genes is their high amino acid (AA) sequence homology and conserved gene organization. These enzymes mediate the biosynthesis of polyketide natural products with enormous structural complexity and chemical nature by combinatorial use of various domains. Therefore, deciphering the order of AA sequence encoded by PKS domains tailored the chemical structure of polyketide analogs still remains a great challenge. The present work deals with an in vitro and in silico analysis of PKS type II genes from five actinobacterial species to correlate KS domain architecture and structural features. Our present analysis reveals the unique protein domain organization of iterative type II PKS and KS domain of marine actinobacteria. The findings of this study would have implications in metabolic pathway reconstruction and design of semi-synthetic genomes to achieve rational design of novel natural products. PMID- 26903958 TI - Reassortment of Avian Influenza A/H6N6 Viruses from Live Poultry Markets in Guangdong, China. AB - Since early 2013, H7N9-subtype avian influenza virus (AIV) has caused human infection in eastern China. To evaluate AIV contamination and the public risk of infection, we systematically implemented environmental sampling from live poultry markets in Guangdong Province. Through real-time polymerase chain reaction assays and next-generation sequencing, we generated full nucleotide sequences of all 10 H6N6 AIVs isolated during sampling. Focusing on sequence analyses of hemagglutinin genes of the 10 H6N6 AIVs revealed that the viruses were low pathogenic AIVs with the typical hemagglutinin cleavage site of P-Q-I-E-T-R-G. The hemagglutinin, neuraminidase, and nucleocapsid genes of nine AIVs were of ST2853-like (H6-subtype) lineage, ST192-like (N6-subtype) lineage, and HN573-like (H6-subtype) lineage, respectively; whereas the other five genes were of ST339 like (H6-subtype) lineage. However, the polymerase PB2 and nucleocapsid genes of one strain (HZ057) were of GS/GD-like (H5N1-subtype) and ST339-like lineages. Phylogenic analysis revealed that all eight genes of the 10 viruses belonged to Eurasian avian lineage. Altogether, the 10 AIVs were reassortants of different genetic groups of exchanges with the same virus subtype, thus illustrating the genetic diversity and complexity of H6N6-subtype AIVs in Guangdong Province. PMID- 26903959 TI - Carbon and Nitrogen Uptake of Calcareous Benthic Foraminifera along a Depth Related Oxygen Gradient in the OMZ of the Arabian Sea. AB - Foraminifera are an important faunal element of the benthos in oxygen-depleted settings such as Oxygen Minimum Zones (OMZs) where they can play a relevant role in the processing of phytodetritus. We investigated the uptake of phytodetritus (labeled with (13)C and (15)N) by calcareous foraminifera in the 0-1 cm sediment horizon under different oxygen concentrations within the OMZ in the eastern Arabian Sea. The in situ tracer experiments were carried out along a depth transect on the Indian margin over a period of 4 to 10 days. The uptake of phytodetrital carbon within 4 days by all investigated species shows that phytodetritus is a relevant food source for foraminifera in OMZ sediments. The decrease of total carbon uptake from 540 to 1100 m suggests a higher demand for carbon by species in the low-oxygen core region of the OMZ or less food competition with macrofauna. Especially Uvigerinids showed high uptake of phytodetrital carbon at the lowest oxygenated site. Variation in the ratio of phytodetrital carbon to nitrogen between species and sites indicates that foraminiferal carbon and nitrogen use can be decoupled and different nutritional demands are found between species. Lower ratio of phytodetrital carbon and nitrogen at 540 m could hint for greater demand or storage of food-based nitrogen, ingestion, or hosting of bacteria under almost anoxic conditions. Shifts in the foraminiferal assemblage structure (controlled by oxygen or food availability) and in the presence of other benthic organisms are likely to account for observed changes in the processing of phytodetritus in the different OMZ habitats. Foraminifera dominate the short-term processing of phytodetritus in the OMZ core but are less important in the lower OMZ boundary region of the Indian margin as biological interactions and species distribution of foraminifera change with depth and oxygen levels. PMID- 26903960 TI - Back to the Future of Soil Metagenomics. PMID- 26903961 TI - Geographic Distribution of Archaeal Ammonia Oxidizing Ecotypes in the Atlantic Ocean. AB - In marine ecosystems, Thaumarchaeota are most likely the major ammonia oxidizers. While ammonia concentrations vary by about two orders of magnitude in the oceanic water column, archaeal ammonia oxidizers (AOA) vary by only one order of magnitude from surface to bathypelagic waters. Thus, the question arises whether the key enzyme responsible for ammonia oxidation, ammonia monooxygenase (amo), exhibits different affinities to ammonia along the oceanic water column and consequently, whether there are different ecotypes of AOA present in the oceanic water column. We determined the abundance and phylogeny of AOA based on their amoA gene. Two ecotypes of AOA exhibited a distribution pattern reflecting the reported availability of ammonia and the physico-chemical conditions throughout the Atlantic, and from epi- to bathypelagic waters. The distinction between these two ecotypes was not only detectable at the nucleotide level. Consistent changes were also detected at the amino acid level. These changes include substitutions of polar to hydrophobic amino acid, and glycine substitutions that could have an effect on the configuration of the amo protein and thus, on its activity. Although we cannot identify the specific effect, the ratio of non-synonymous to synonymous substitutions (dN/dS) between the two ecotypes indicates a strong positive selection between them. Consequently, our results point to a certain degree of environmental selection on these two ecotypes that have led to their niche specialization. PMID- 26903963 TI - Viral Regulation of Prokaryotic Carbon Metabolism in a Hypereutrophic Freshwater Reservoir Ecosystem (Villerest, France). AB - The current consensus concerning the viral regulation of prokaryotic carbon metabolism is less well-studied, compared to substrate availability. We explored the seasonal and vertical distribution of viruses and its relative influence on prokaryotic carbon metabolism in a hypereutrophic reservoir, Lake Villerest (France). Flow cytometry and transmission electron microscopy (TEM) analyses to determine viral abundance (VA; range = 6.1-63.5 * 10(7) ml(-1)) and viral infection rates of prokaryotes (range = 5.3-32%) respectively suggested that both the parameters varied more significantly with depths than with seasons. Prokaryotic growth efficiency (PGE, considered as a proxy of prokaryotic carbon metabolism) calculated from prokaryotic production and respiration measurements (PGE = prokaryotic production/[prokaryotic production + prokaryotic respiration] * 100) varied from 14 to 80% across seasons and depths. Viruses through selective lyses had antagonistic impacts on PGE by regulating key prokaryotic metabolic processes (i.e., production and respiration). Higher viral lysis accompanied by higher respiration rates and lower PGE in the summer (mean = 22.9 +/- 10.3%) than other seasons (mean = 59.1 +/- 18.6%), led to significant loss of carbon through bacterial-viral loop and shifted the reservoir system to net heterotrophy. Our data therefore suggests that the putative adverse impact of viruses on the growth efficiency of the prokaryotic community can have strong implications on nutrient flux patterns and on the overall ecosystem metabolism in anthropogenic dominated aquatic systems such as Lake Villerest. PMID- 26903962 TI - Streptomyces Bacteria as Potential Probiotics in Aquaculture. AB - In response to the increased seafood demand from the ever-going human population, aquaculture has become the fastest growing animal food-producing sector. However, the indiscriminate use of antibiotics as a biological control agents for fish pathogens has led to the emergence of antibiotic resistance bacteria. Probiotics are defined as living microbial supplement that exert beneficial effects on hosts as well as improvement of environmental parameters. Probiotics have been proven to be effective in improving the growth, survival and health status of the aquatic livestock. This review aims to highlight the genus Streptomyces can be a good candidate for probiotics in aquaculture. Studies showed that the feed supplemented with Streptomyces could protect fish and shrimp from pathogens as well as increase the growth of the aquatic organisms. Furthermore, the limitations of Streptomyces as probiotics in aquaculture is also highlighted and solutions are discussed to these limitations. PMID- 26903965 TI - Dysbiosis May Trigger Autoimmune Diseases via Inappropriate Post-Translational Modification of Host Proteins. AB - The gut ecosystem with myriads of microorganisms and the high concentration of immune system cells can be considered as a separate organ on its own. The balanced interaction between the host and microbial cells has been shaped during the long co-evolutionary process. In dysbiotic conditions, however, this balance is compromised and results in abnormal interaction between the host and microbiota. It is hypothesize here that the changed spectrum of microbial enzymes involved in post-translational modification of proteins (PTMP) may contribute to the aberrant modification of host proteins thus generating autoimmune responses by the host, resulting in autoimmune diseases. PMID- 26903964 TI - Effects of Trace Metal Concentrations on the Growth of the Coral Endosymbiont Symbiodinium kawagutii. AB - Symbiodinium is an indispensable endosymbiont in corals and the most important primary producer in coral reef ecosystems. During the past decades, coral bleaching attributed to the disruption of the symbiosis has frequently occurred resulting in reduction of coral reef coverage globally. Growth and proliferation of corals require some specific trace metals that are essential components of pertinent biochemical processes, such as in photosynthetic systems and electron transport chains. In addition, trace metals are vital in the survival of corals against oxidative stress because these metals serve as enzymatic cofactors in antioxidative defense mechanisms. The basic knowledge about trace metal requirements of Symbiodinium is lacking. Here we show that the requirement of Symbiodinium kawagutii for antioxidant-associated trace metals exhibits the following order: Fe >> Cu/Zn/Mn >> Ni. In growth media with Cu, Zn, Mn, and varying Fe concentrations, we observed that Cu, Zn, and Mn cellular quotas were inversely related to Fe concentrations. In the absence of Cu, Zn, and Mn, growth rates increased with increasing inorganic Fe concentrations up to 1250 pM, indicating the relatively high Fe requirement for Symbiodinium growth and potential functional complementarity of these metals. These results demonstrate the relative importance of trace metals to sustain Symbiodinium growth and a potential metal inter replacement strategy in Symbiodinium to ensure survival of coral reefs in an oligotrophic and stressful environment. PMID- 26903966 TI - Genetic Diversity and Positive Selection Analysis of Classical Swine Fever Virus Envelope Protein Gene E2 in East China under C-Strain Vaccination. AB - Classical swine fever virus (CSFV) causes an economically important and highly contagious disease of pigs worldwide. C-strain vaccination is one of the most effective ways to contain this disease. Since 2014, sporadic CSF outbreaks have been occurring in some C-strain vaccinated provinces of China. To decipher the disease etiology, 25 CSFV E2 genes from 169 clinical samples were cloned and sequenced. Phylogenetic analyses revealed that all 25 isolates belonged to subgenotype 2.1. Twenty-three of the 25 isolates were clustered in a newly defined subgenotype, 2.1d, and shared some consistent molecular characteristics. To determine whether the complete E2 gene was under positive selection pressure, we used a site-by-site analysis to identify specific codons that underwent evolutionary selection, and seven positively selected codons were found. Three positively selected sites (amino acids 17, 34, and 72) were identified in antigenicity-relevant domains B/C of the amino-terminal half of the E2 protein. In addition, another positively selected site (amino acid 200) exhibited a polarity change from hydrophilic to hydrophobic, which may change the antigenicity and virulence of CSFV. The results indicate that the circulating CSFV strains in Shandong province were mostly clustered in subgenotype 2.1d. Moreover, the identification of these positively selected sites could help to reveal molecular determinants of virulence or pathogenesis, and to clarify the driving force of CSFV evolution in East China. PMID- 26903967 TI - Adaptation of Staphylococcus xylosus to Nutrients and Osmotic Stress in a Salted Meat Model. AB - Staphylococcus xylosus is commonly used as starter culture for meat fermentation. Its technological properties are mainly characterized in vitro, but the molecular mechanisms for its adaptation to meat remain unknown. A global transcriptomic approach was used to determine these mechanisms. S. xylosus modulated the expression of about 40-50% of the total genes during its growth and survival in the meat model. The expression of many genes involved in DNA machinery and cell division, but also in cell lysis, was up-regulated. Considering that the S. xylosus population remained almost stable between 24 and 72 h of incubation, our results suggest a balance between cell division and cell lysis in the meat model. The expression of many genes encoding enzymes involved in glucose and lactate catabolism was up-regulated and revealed that glucose and lactate were used simultaneously. S. xylosus seemed to adapt to anaerobic conditions as revealed by the overexpression of two regulatory systems and several genes encoding cofactors required for respiration. In parallel, genes encoding transport of peptides and peptidases that could furnish amino acids were up-regulated and thus concomitantly a lot of genes involved in amino acid synthesis were down regulated. Several genes involved in glutamate homeostasis were up-regulated. Finally, S. xylosus responded to the osmotic stress generated by salt added to the meat model by overexpressing genes involved in transport and synthesis of osmoprotectants, and Na(+) and H(+) extrusion. PMID- 26903968 TI - Autoinducer-2 of Streptococcus mitis as a Target Molecule to Inhibit Pathogenic Multi-Species Biofilm Formation In Vitro and in an Endotracheal Intubation Rat Model. AB - Streptococcus mitis (S. mitis) and Pseudomonas aeruginosa (P. aeruginosa) are typically found in the upper respiratory tract of infants. We previously found that P. aeruginosa and S. mitis were two of the most common bacteria in biofilms on newborns' endotracheal tubes (ETTs) and in their sputa and that S. mitis was able to produce autoinducer-2 (AI-2), whereas P. aeruginosa was not. Recently, we also found that exogenous AI-2 and S. mitis could influence the behaviors of P. aeruginosa. We hypothesized that S. mitis contributes to this interspecies interaction and that inhibition of AI-2 could result in inhibition of these effects. To test this hypothesis, we selected PAO1 as a representative model strain of P. aeruginosa and evaluated the effect of S. mitis as well as an AI-2 analog (D-ribose) on mono- and co-culture biofilms in both in vitro and in vivo models. In this context, S. mitis promoted PAO1 biofilm formation and pathogenicity. Dual-species (PAO1 and S. mitis) biofilms exhibited higher expression of quorum sensing genes than single-species (PAO1) biofilms did. Additionally, ETTs covered in dual-species biofilms increased the mortality rate and aggravated lung infection compared with ETTs covered in mono-species biofilms in an endotracheal intubation rat model, all of which was inhibited by D-ribose. Our results demonstrated that S. mitis AI-2 plays an important role in interspecies interactions with PAO1 and may be a target for inhibition of biofilm formation and infection in ventilator-associated pneumonia. PMID- 26903969 TI - Comparative Analysis of Salivary Gland Proteomes of Two Glossina Species that Exhibit Differential Hytrosavirus Pathologies. AB - Glossina pallidipes salivary gland hypertrophy virus (GpSGHV; family Hytrosaviridae) is a dsDNA virus exclusively pathogenic to tsetse flies (Diptera; Glossinidae). The 190 kb GpSGHV genome contains 160 open reading frames and encodes more than 60 confirmed proteins. The asymptomatic GpSGHV infection in flies can convert to symptomatic infection that is characterized by overt salivary gland hypertrophy (SGH). Flies with SGH show reduced general fitness and reproductive dysfunction. Although the occurrence of SGH is an exception rather than the rule, G. pallidipes is thought to be the most susceptible to expression of overt SGH symptoms compared to other Glossina species that are largely asymptomatic. Although Glossina salivary glands (SGs) play an essential role in GpSGHV transmission, the functions of the salivary components during the virus infection are poorly understood. In this study, we used mass spectrometry to study SG proteomes of G. pallidipes and G. m. morsitans, two Glossina model species that exhibit differential GpSGHV pathologies (high and low incidence of SGH, respectively). A total of 540 host proteins were identified, of which 23 and 9 proteins were significantly up- and down-regulated, respectively, in G. pallidipes compared to G. m. morsitans. Whereas 58 GpSGHV proteins were detected in G. pallidipes F1 progenies, only 5 viral proteins were detected in G. m. morsitans. Unlike in G. pallidipes, qPCR assay did not show any significant increase in virus titers in G. m. morsitans F1 progenies, confirming that G. m. morsitans is less susceptible to GpSGHV infection and replication compared to G. pallidipes. Based on our results, we speculate that in the case of G. pallidipes, GpSGHV employs a repertoire of host intracellular signaling pathways for successful infection. In the case of G. m. morsitans, antiviral responses appeared to be dominant. These results are useful for designing additional tools to investigate the Glossina-GpSGHV interactions. PMID- 26903970 TI - Anti-parasitic Peptides from Arthropods and their Application in Drug Therapy. AB - Africa, Asia, and Latin America are regions highly affected by endemic diseases, such as Leishmaniasis, Malaria, and Chagas' disease. They are responsible for the death of 1000s of patients every year, as there is not yet a cure for them and the drugs used are inefficient against the pathogenic parasites. During the life cycle of some parasitic protozoa, insects become the most important host and disseminator of the diseases triggered by these microorganisms. As infected insects do not develop nocive symptoms, they can carry the parasites for long time inside their body, enabling their multiplication and life cycle completion. Eventually, parasites infect human beings after insect's transmission through their saliva and/or feces. Hence, host insects and general arthropods, which developed a way to coexist with such parasites, are a promising source for the prospection of anti-parasitic compounds, as alternative methods for the treatment of protozoa-related diseases. Among the molecules already isolated and investigated, there are proteins and peptides with high activity against parasites, able to inhibit parasite activity in different stages of development. Although, studies are still taking their first steps, initial results show new perspectives on the treatment of parasitic diseases. Therefore, in this report, we describe about peptides from host insect sources with activity against the three most endemic parasites: Leishmania sp., Plasmodium sp., and Trypanosomes. Moreover, we discuss the future application insect peptides as anti-parasitic drugs and the use of non-hosts insect transcriptomes on the prospection of novel molecules for the treatment of parasitic neglected diseases. PMID- 26903972 TI - From Farm to Table: Follow-Up of Shiga Toxin-Producing Escherichia coli Throughout the Pork Production Chain in Argentina. AB - Pigs are important reservoirs of Shiga toxin-producing Escherichia coli (STEC). The entrance of these strains into the food chain implies a risk to consumers because of the severity of hemolytic uremic syndrome. This study reports the prevalence and characterization of STEC throughout the pork production chain. From 764 samples, 31 (4.05%) were stx positive by PCR screening. At farms, 2.86% of samples were stx positive; at slaughter, 4.08% of carcasses were stx positive and at boning rooms, 6% of samples were stx positive. These percentages decreased in pork meat ready for sale at sales markets (4.59%). From positive samples, 50 isolates could be characterized. At farms 37.5% of the isolates carried stx1/stx2 genes, 37.5% possessed stx2e and 25%, carried only stx2. At slaughter we detected 50% of isolates positive for stx2, 33% for stx2e, and 16% for stx1/stx2. At boning rooms 59% of the isolates carried stx1/stx2, 14% stx2e, and 5% stx1/stx2/stx2e. At retail markets 66% of isolates were positive for stx2, 17% stx2e, and 17% stx1/stx2. For the other virulence factors, ehxA and saa were not detected and eae gene was detected in 12% of the isolates. Concerning putative adhesins, agn43 was detected in 72%, ehaA in 26%, aida in 8%, and iha in 6% of isolates. The strains were typed into 14 E. coli O groups (O1, O2, O8, O15, O20, O35, O69, O78, O91, O121, O138, O142, O157, O180) and 10 H groups (H9, H10, H16, H21, H26, H29, H30, H32, H45, H46). This study reports the prevalence and characterization of STEC strains through the chain pork suggesting the vertical transmission. STEC contamination originates in the farms and is transferred from pigs to carcasses in the slaughter process and increase in meat pork at boning rooms and sales markets. These results highlight the need to implement an integrated STEC control system based on good management practices on the farm and critical control point systems in the food chain. PMID- 26903971 TI - Short-Term Rhizosphere Effect on Available Carbon Sources, Phenanthrene Degradation, and Active Microbiome in an Aged-Contaminated Industrial Soil. AB - Over the last decades, understanding of the effects of plants on soil microbiomes has greatly advanced. However, knowledge on the assembly of rhizospheric communities in aged-contaminated industrial soils is still limited, especially with regard to transcriptionally active microbiomes and their link to the quality or quantity of carbon sources. We compared the short-term (2-10 days) dynamics of bacterial communities and potential PAH-degrading bacteria in bare or ryegrass planted aged-contaminated soil spiked with phenanthrene, put in relation with dissolved organic carbon (DOC) sources and polycyclic aromatic hydrocarbon (PAH) pollution. Both resident and active bacterial communities (analyzed from DNA and RNA, respectively) showed higher species richness and smaller dispersion between replicates in planted soils. Root development strongly favored the activity of Pseudomonadales within the first 2 days, and of members of Actinobacteria, Caulobacterales, Rhizobiales, and Xanthomonadales within 6-10 days. Plants slowed down the dissipation of phenanthrene, while root exudation provided a cocktail of labile substrates that might preferentially fuel microbial growth. Although the abundance of PAH-degrading genes increased in planted soil, their transcription level stayed similar to bare soil. In addition, network analysis revealed that plants induced an early shift in the identity of potential phenanthrene degraders, which might influence PAH dissipation on the long-term. PMID- 26903973 TI - CyDiv, a Conserved and Novel Filamentous Cyanobacterial Cell Division Protein Involved in Septum Localization. AB - Cell division in bacteria has been studied mostly in Escherichia coli and Bacillus subtilis, model organisms for Gram-negative and Gram-positive bacteria, respectively. However, cell division in filamentous cyanobacteria is poorly understood. Here, we identified a novel protein, named CyDiv (Cyanobacterial Division), encoded by the all2320 gene in Anabaena sp. PCC 7120. We show that CyDiv plays a key role during cell division. CyDiv has been previously described only as an exclusive and conserved hypothetical protein in filamentous cyanobacteria. Using polyclonal antibodies against CyDiv, we showed that it localizes at different positions depending on cell division timing: poles, septum, in both daughter cells, but also in only one of the daughter cells. The partial deletion of CyDiv gene generates partial defects in cell division, including severe membrane instability and anomalous septum localization during late division. The inability to complete knock out CyDiv strains suggests that it is an essential gene. In silico structural protein analyses and our experimental results suggest that CyDiv is an FtsB/DivIC-like protein, and could therefore, be part of an essential late divisome complex in Anabaena sp. PCC 7120. PMID- 26903974 TI - Structure and Interactions of a Dimeric Variant of sHIP, a Novel Virulence Determinant of Streptococcus pyogenes. AB - Streptococcus pyogenes is one of the most significant bacterial pathogens in the human population mostly causing superficial and uncomplicated infections (pharyngitis and impetigo) but also invasive and life-threatening disease. We have previously identified a virulence determinant, protein sHIP, which is secreted at higher levels by an invasive compared to a non-invasive strain of S. pyogenes. The present work presents a further characterization of the structural and functional properties of this bacterial protein. Biophysical and structural studies have shown that protein sHIP forms stable tetramers both in the crystal and in solution. The tetramers are composed of four helix-loop-helix motifs with the loop regions connecting the helices displaying a high degree of flexibility. Owing to interactions at the tetramer interface, the observed tetramer can be described as a dimer of dimers. We identified three residues at the tetramer interface (Leu84, Leu88, Tyr95), which due to largely non-polar side-chains, could be important determinants for protein oligomerization. Based on these observations, we produced a sHIP variant in which these residues were mutated to alanines. Biophysical experiments clearly indicated that the sHIP mutant appear only as dimers in solution confirming the importance of the interfacial residues for protein oligomerisation. Furthermore, we could show that the sHIP mutant interacts with intact histidine-rich glycoprotein (HRG) and the histidine-rich repeats in HRG, and inhibits their antibacterial activity to the same or even higher extent as compared to the wild type protein sHIP. We determined the crystal structure of the sHIP mutant, which, as a result of the high quality of the data, allowed us to improve the existing structural model of the protein. Finally, by employing NMR spectroscopy in solution, we generated a model for the complex between the sHIP mutant and an HRG-derived heparin-binding peptide, providing further molecular details into the interactions involving protein sHIP. PMID- 26903977 TI - Anaerobic Nitrogen Turnover by Sinking Diatom Aggregates at Varying Ambient Oxygen Levels. AB - In the world's oceans, even relatively low oxygen levels inhibit anaerobic nitrogen cycling by free-living microbes. Sinking organic aggregates, however, might provide oxygen-depleted microbial hotspots in otherwise oxygenated surface waters. Here, we show that sinking diatom aggregates can host anaerobic nitrogen cycling at ambient oxygen levels well above the hypoxic threshold. Aggregates were produced from the ubiquitous diatom Skeletonema marinoi and the natural microbial community of seawater. Microsensor profiling through the center of sinking aggregates revealed internal anoxia at ambient 40% air saturation (~100 MUmol O2 L(-1)) and below. Accordingly, anaerobic nitrate turnover inside the aggregates was evident within this range of ambient oxygen levels. In incubations with (15)N-labeled nitrate, individual Skeletonema aggregates produced NO2 (-) (up to 10.7 nmol N h(-1) per aggregate), N2 (up to 7.1 nmol N h(-1)), NH4 (+) (up to 2.0 nmol N h(-1)), and N2O (up to 0.2 nmol N h(-1)). Intriguingly, nitrate stored inside the diatom cells served as an additional, internal nitrate source for dinitrogen production, which may partially uncouple anaerobic nitrate turnover by diatom aggregates from direct ambient nitrate supply. Sinking diatom aggregates can contribute directly to fixed-nitrogen loss in low-oxygen environments in the ocean and vastly expand the ocean volume in which anaerobic nitrogen turnover is possible, despite relatively high ambient oxygen levels. Depending on the extent of intracellular nitrate consumption during the sinking process, diatom aggregates may also be involved in the long-distance export of nitrate to the deep ocean. PMID- 26903976 TI - Proteomic Profiling of Bifidobacterium bifidum S17 Cultivated Under In Vitro Conditions. AB - Bifidobacteria are frequently used in probiotic food and dairy products. Bifidobacterium bifidum S17 is a promising probiotic candidate strain that displays strong adhesion to intestinal epithelial cells and elicits potent anti inflammatory capacity both in vitro and in murine models of colitis. The recently sequenced genome of B. bifidum S17 has a size of about 2.2 Mb and encodes 1,782 predicted protein-coding genes. In the present study, a comprehensive proteomic profiling was carried out to identify and characterize proteins expressed by B. bifidum S17. A total of 1148 proteins entries were identified by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), representing 64.4% of the predicted proteome. 719 proteins could be assigned to functional categories according to cluster of orthologous groups of proteins (COGs). The COG distribution of the detected proteins highly correlates with that of the complete predicted proteome suggesting a good coverage and representation of the genomic content of B. bifidum S17 by the proteome. COGs that were highly present in the proteome of B. bifidum S17 were Translation, Amino Acid Transport and Metabolism, and Carbohydrate Transport and Metabolism. Complete sets of enzymes for both the bifidus shunt and the Embden-Meyerh of pathway were identified. Further bioinformatic analysis yielded 28 proteins with a predicted extracellular localization including 14 proteins with an LPxTG-motif for cell wall anchoring and two proteins (elongation factor Tu and enolase) with a potential moonlighting function in adhesion. Amongst the predicted extracellular proteins were five of six pilin proteins encoded in the B. bifidum S17 genome as well as several other proteins with a potential role in interaction with host structures. The presented results are the first compilation of a proteomic reference profile for a B. bifidum strain and will facilitate analysis of the molecular mechanisms of physiology, host-interactions and beneficial effects of a potential probiotic strain. PMID- 26903975 TI - The Lysobacter capsici AZ78 Genome Has a Gene Pool Enabling it to Interact Successfully with Phytopathogenic Microorganisms and Environmental Factors. AB - Lysobacter capsici AZ78 has considerable potential for biocontrol of phytopathogenic microorganisms. However, lack of information about genetic cues regarding its biological characteristics may slow down its exploitation as a biofungicide. In order to obtain a comprehensive overview of genetic features, the L. capsici AZ78 genome was sequenced, annotated and compared with the phylogenetically related pathogens Stenotrophomonas malthophilia K729a and Xanthomonas campestris pv. campestris ATCC 33913. Whole genome comparison, supported by functional analysis, indicated that L. capsici AZ78 has a larger number of genes responsible for interaction with phytopathogens and environmental stress than S. malthophilia K729a and X. c. pv. campestris ATCC 33913. Genes involved in the production of antibiotics, lytic enzymes and siderophores were specific for L. capsici AZ78, as well as genes involved in resistance to antibiotics, environmental stressors, fungicides and heavy metals. The L. capsici AZ78 genome did not encompass genes involved in infection of humans and plants included in the S. malthophilia K729a and X. c. pv. campestris ATCC 33913 genomes, respectively. The L. capsici AZ78 genome provides a genetic framework for detailed analysis of other L. capsici members and the development of novel biofungicides based on this bacterial strain. PMID- 26903978 TI - Hydrogenase Gene Distribution and H2 Consumption Ability within the Thiomicrospira Lineage. AB - Thiomicrospira were originally characterized as sulfur-oxidizing chemolithoautotrophs. Attempts to grow them on hydrogen failed for many years. Only recently we demonstrated hydrogen consumption among two of three tested Thiomicrospira and posited that hydrogen consumption may be more widespread among Thiomicrospira than previously assumed. Here, we investigate and compare the hydrogen consumption ability and the presence of group 1 [NiFe]-hydrogenase genes (enzyme catalyzes H2<->2H(+) + 2e(-)) for sixteen different Thiomicrospira species. Seven of these Thiomicrospira species encoded group 1 [NiFe]-hydrogenase genes and five of these species could also consume hydrogen. All Thiomicrospira species exhibiting hydrogen consumption were from hydrothermal vents along the Mid-Atlantic ridge or Eastern Pacific ridges. The tested Thiomicrospira from Mediterranean and Western Pacific vents could not consume hydrogen. The [NiFe] hydrogenase genes were categorized into two clusters: those resembling the hydrogenase from Hydrogenovibrio are in cluster I and are related to those from Alpha- and other Gammaproteobacteria. In cluster II, hydrogenases found exclusively in Thiomicrospira crunogena strains are combined and form a monophyletic group with those from Epsilonproteobacteria suggesting they were acquired through horizontal gene transfer. Hydrogen consumption appears to be common among some Thiomicrospira, given that five of the tested sixteen strains carried this trait. The hydrogen consumption ability expands their competitiveness within an environment. PMID- 26903980 TI - Functional Analysis of the Citrate Activator CitO from Enterococcus faecalis Implicates a Divalent Metal in Ligand Binding. AB - The regulator of citrate metabolism, CitO, from Enterococcus faecalis belongs to the FCD family within the GntR superfamily. In the presence of citrate, CitO binds to cis-acting sequences located upstream of the cit promoters inducing the expression of genes involved in citrate utilization. The quantification of the molecular binding affinities, performed by isothermal titration calorimetry (ITC), indicated that CitO has a high affinity for citrate (K D = 1.2 +/- 0.2 MUM), while it did not recognize other metabolic intermediates. Based on a structural model of CitO where a putative small molecule and a metal binding site were identified, it was hypothesized that the metal ion is required for citrate binding. In agreement with this model, citrate binding to CitO sharply decreased when the protein was incubated with EDTA. This effect was reverted by the addition of Ni(2+), and Zn(2+) to a lesser extent. Structure-based site-directed mutagenesis was conducted and it was found that changes to alanine in residues Arg97 and His191 resulted in decreased binding affinities for citrate, as determined by EMSA and ITC. Further assays using lacZ fusions confirmed that these residues in CitO are involved in sensing citrate in vivo. These results indicate that the molecular modifications induced by a ligand and a metal binding in the C-terminal domain of CitO are required for optimal DNA binding activity, and consequently, transcriptional activation. PMID- 26903979 TI - Sister Dehalobacter Genomes Reveal Specialization in Organohalide Respiration and Recent Strain Differentiation Likely Driven by Chlorinated Substrates. AB - The genomes of two closely related Dehalobacter strains (strain CF and strain DCA) were assembled from the metagenome of an anaerobic enrichment culture that reductively dechlorinates chloroform (CF), 1,1,1-trichloroethane (1,1,1-TCA) and 1,1-dichloroethane (1,1-DCA). The 3.1 Mbp genomes of strain CF (that dechlorinates CF and 1,1,1-TCA) and strain DCA (that dechlorinates 1,1-DCA) each contain 17 putative reductive dehalogenase homologous (rdh) genes. These two genomes were systematically compared to three other available organohalide respiring Dehalobacter genomes (Dehalobacter restrictus strain PER-K23, Dehalobacter sp. strain E1 and Dehalobacter sp. strain UNSWDHB), and to the genomes of Dehalococcoides mccartyi strain 195 and Desulfitobacterium hafniense strain Y51. This analysis compared 42 different metabolic and physiological categories. The genomes of strains CF and DCA share 90% overall average nucleotide identity and >99.8% identity over a 2.9 Mbp alignment that excludes large insertions, indicating that these genomes differentiated from a close common ancestor. This differentiation was likely driven by selection pressures around two orthologous reductive dehalogenase genes, cfrA and dcrA, that code for the enzymes that reduce CF or 1,1,1-TCA and 1,1-DCA. The many reductive dehalogenase genes found in the five Dehalobacter genomes cluster into two small conserved regions and were often associated with Crp/Fnr transcriptional regulators. Specialization is on-going on a strain-specific basis, as some strains but not others have lost essential genes in the Wood-Ljungdahl (strain E1) and corrinoid biosynthesis pathways (strains E1 and PER-K23). The gene encoding phosphoserine phosphatase, which catalyzes the last step of serine biosynthesis, is missing from all five Dehalobacter genomes, yet D. restrictus can grow without serine, suggesting an alternative or unrecognized biosynthesis route exists. In contrast to D. mccartyi, a complete heme biosynthesis pathway is present in the five Dehalobacter genomes. This pathway corresponds to a newly described alternative heme biosynthesis route first identified in Archaea. This analysis of organohalide-respiring Firmicutes and Chloroflexi reveals profound evolutionary differences despite very similar niche-specific metabolism and function. PMID- 26903981 TI - Antibiofilm and Anti-Infection of a Marine Bacterial Exopolysaccharide Against Pseudomonas aeruginosa. AB - Pseudomonas aeruginosa is a well-known pathogenic bacterium that forms biofilms and produces virulence factors, thus leading to major problems in many fields, such as clinical infection, food contamination, and marine biofouling. In this study, we report the purification and characterization of an exopolysaccharide EPS273 from the culture supernatant of marine bacterium P. stutzeri 273. The exopolysaccharide EPS273 not only effectively inhibits biofilm formation but also disperses preformed biofilm of P. aeruginosa PAO1. High performance liquid chromatography traces of the hydrolyzed polysaccharides shows that EPS273 primarily consists of glucosamine, rhamnose, glucose and mannose. Further investigation demonstrates that EPS273 reduces the production of the virulence factors pyocyanin, exoprotease, and rhamnolipid, and the virulence of P. aeruginosa PAO1 to human lung cells A549 and zebrafish embryos is also obviously attenuated by EPS273. In addition, EPS273 also greatly reduces the production of hydrogen peroxide (H2O2) and extracellular DNA (eDNA), which are important factors for biofilm formation. Furthermore, EPS273 exhibits strong antioxidant potential by quenching hydroxyl and superoxide anion radicals. Notably, the antibiofouling activity of EPS273 is observed in the marine environment up to 2 weeks according to the amounts of bacteria and diatoms in the glass slides submerged in the ocean. Taken together, the properties of EPS273 indicate that it has a promising prospect in combating bacterial biofilm-associated infection, food-processing contamination and marine biofouling. PMID- 26903983 TI - MALDI-TOF Mass Spectrometry Discriminates Known Species and Marine Environmental Isolates of Pseudoalteromonas. AB - The genus Pseudoalteromonas constitutes an ecologically significant group of marine Gammaproteobacteria with potential biotechnological value as producers of bioactive compounds and of enzymes. Understanding their roles in the environment and bioprospecting for novel products depend on efficient ways of identifying environmental isolates. Matrix Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) biotyping has promise as a rapid and reliable method of identifying and distinguishing between different types of bacteria, but has had relatively limited application to marine bacteria and has not been applied systematically to Pseudoalteromonas. Therefore, we constructed a MALDI-TOF MS database of 31 known Pseudoalteromonas species, to which new isolates can be compared by MALDI-TOF biotyping. The ability of MALDI-TOF MS to distinguish between species was scrutinized by comparison with 16S rRNA gene sequencing. The patterns of similarity given by the two approaches were broadly but not completely consistent. In general, the resolution of MALDI-TOF MS was greater than that of 16S rRNA gene sequencing. The database was tested with 13 environmental Pseudoalteromonas isolates from UK waters. All of the test strains could be identified to genus level by MALDI-TOF MS biotyping, but most could not be definitely identified to species level. We conclude that several of these isolates, and possibly most, represent new species. Thus, further taxonomic investigation of Pseudoalteromonas is needed before MALDI-TOF MS biotyping can be used reliably for species identification. It is, however, a powerful tool for characterizing and distinguishing among environmental isolates and can make an important contribution to taxonomic studies. PMID- 26903982 TI - Interactions of Opioids and HIV Infection in the Pathogenesis of Chronic Pain. AB - Over 50% of HIV-1/AIDS patients suffer chronic pain. Currently, opioids are the cornerstone medications for treating severe pain in these patients. Ironically, emerging clinical data indicates that repeated use of opiate pain medicines might in fact heighten the chronic pain states in HIV patients. Both laboratory-based and clinical studies strongly suggest that opioids exacerbate the detrimental effects of HIV-1 infection on the nervous system, both on neurons and glia. The combination of opioids and HIV-1infection may promote the damage of neurons, including those in the pain sensory and transmission pathway, by activating both caspase-dependent and caspase-independent pro-apoptotic pathways. In addition, the opiate-HIV-1 interaction may also cause widespread disturbance of glial function and elicit glial-derived pro-inflammatory responses that dysregulate neuronal function. The deregulation of neuron-glia cross-talk that occurs with the combination of HIV-1 and opioids appears to play an important role in the development of the pathological pain state. In this article, we wish to provide an overview of the potential molecular and cellular mechanisms by which opioids may interact with HIV-1 to cause neurological problems, especially in the context of HIV-associated pathological pain. Elucidating the underlying mechanisms will help researchers and clinicians to understand how chronic use of opioids for analgesia enhances HIV-associated pain. It will also assist in optimizing therapeutic approaches to prevent or minimize this significant side effect of opiate analgesics in pain management for HIV patients. PMID- 26903986 TI - Some Compositional and Kinetic Controls on the Bioenergetic Landscapes in Oceanic Basement. AB - This contribution assesses the availability of catabolic energy for microbial life during water-rock reactions in the flanks of mid-ocean ridges, where basaltic and ultramafic rocks interact with circulating seawater. In addition to equilibrium thermodynamic computations, results for kinetic reaction paths are presented. In these calculations, it is assumed that dissolution of olivine and basalt glass control the rates of hydrogen forming reactions in ultramafic and basaltic rocks, respectively. The results suggest that all ocean crust basement rocks release enough hydrogen (H2,aq) to support hydrogenotrophic life at low water-to-rock ratios. Olivine dissolution rate control imposes a stronger effect on hydrogen production than phase equilibrium controls, indicating that magnetite formation is not a requirement for production of large amounts of hydrogen in ultramafic rocks. The formation of non-tronite and celadonite are primarily responsible for the formation of the moderate amounts of hydrogen (H2,aq) expected in basaltic ridge flanks. Under conditions of large seawater fluxes required to account for the great global convective heat flow in ridge flanks, however, hydrogen production in basaltic ridge flanks is insufficient for supporting hydrogenotrophic life. It is hence proposed that the role of Fe oxidation in basaltic ridge flanks is greater than previously suggested. A standing stock of 2.4(*)10(28) cells may be supported by Fe oxidation in basaltic ridge flanks, equivalent of about 10% of the sedimentary deep biosphere. The size of a hydrogenotrophic biomass within the ocean crust is more difficult to estimate because the rates and processes of hydrogen release are insufficiently constrained. In any case, hydrogenotrophy in the ocean crust should be of key importance only in olivine-rich basement rocks and in sedimented ridge flanks with low time-integrated seawater fluxes. PMID- 26903985 TI - Molecular Characterization of Gbeta-Like Protein CpcB Involved in Antifungal Drug Susceptibility and Virulence in A. fumigatus. AB - Aspergillus fumigatus is an airborne human fungal pathogen that can survive in a wide range of environmental condition. G protein complex transduces external signals from a variety of stimuli outside a cell to its interior effectors in all eukaryotes. Gbeta-like CpcB (cross pathway control B) belongs to a WD40 repeat protein family with the conserved G-H and W-D residues. Previous studies have demonstrated that Gbeta-like proteins cooperate with related signal transduction proteins to function during many important developmental processes in A. fumigatus. However, the molecular characteristics of Gbeta-like CpcB have not yet been identified. In this study, we demonstrated that the G-H residues in WD repeat 1, 2, 3, and the W-D residue in WD repeat 2 of CpcB are required not only to control normal hyphal growth and conidiation but also to affect antifungal drug susceptibility. The enhanced drug resistance might be due to reduced intracellular drug accumulation and altered ergosterol component. Moreover, we find that the first G-H residue of CpcB plays an important role in the virulence of A. fumigatus. To our knowledge, this is the first report for finding the importance of the conserved G-H and W-D residues for a Gbeta-like protein in understanding of G protein functions. PMID- 26903984 TI - Cryptococcus and Phagocytes: Complex Interactions that Influence Disease Outcome. AB - Cryptococcus neoformans and C. gattii are fungal pathogens that cause life threatening disease. These fungi commonly enter their host via inhalation into the lungs where they encounter resident phagocytes, including macrophages and dendritic cells, whose response has a pronounced impact on the outcome of disease. Cryptococcus has complex interactions with the resident and infiltrating innate immune cells that, ideally, result in destruction of the yeast. These phagocytic cells have pattern recognition receptors that allow recognition of specific cryptococcal cell wall and capsule components. However, Cryptococcus possesses several virulence factors including a polysaccharide capsule, melanin production and secretion of various enzymes that aid in evasion of the immune system or enhance its ability to thrive within the phagocyte. This review focuses on the intricate interactions between the cryptococci and innate phagocytic cells including discussion of manipulation and evasion strategies used by Cryptococcus, anti-cryptococcal responses by the phagocytes and approaches for targeting phagocytes for the development of novel immunotherapeutics. PMID- 26903987 TI - Bacterial-Plant-Interactions: Approaches to Unravel the Biological Function of Bacterial Volatiles in the Rhizosphere. AB - Rhizobacteria produce an enormous amount of volatile compounds, however, the function of these metabolites is scarcely understood. Investigations evaluating influences on plants performed in various laboratories using individually developed experimental setups revealed different and often contradictory results, e.g., ranging from a significant plant growth promotion to a dramatic suppression of plant development. In addition to these discrepancies, these test systems neglected properties and complexity of the rhizosphere. Therefore, to pursue further investigations of the role of bacterial volatiles in this underground habitat, the applied methods have to simulate its natural characteristics as much as possible. In this review, we will describe and discuss pros and cons of currently used bioassays, give insights into rhizosphere characteristics, and suggest improvements for test systems that would consider in natura conditions and would allow gaining further knowledge of the potential function and significance of rhizobacterial volatiles in plant life. PMID- 26903988 TI - Complete Genome Sequence Analysis of Pandoraea pnomenusa Type Strain DSM 16536(T) Isolated from a Cystic Fibrosis Patient. PMID- 26903990 TI - Ionic Liquids as Unforeseen Assets to Fight Life-Threatening Mycotic Diseases. AB - Ionic liquids discovery has celebrated 100 years. They consist solely of ions, one of which is typically organic and asymmetrical. Remarkable physical and chemical properties stirred their use as alternative solvents in many chemical processes. The recent demonstration of their occurrence in nature might boost their interest in biological sciences. In the search of mechanistic understandings of ionic liquids' ecotoxicological impacts in fungi, we have analyzed the proteome, transcriptome, and metabolome responses to this chemical stress. Data illuminated new hypotheses that altered our research path - exploit ionic liquids as tools for the discovery of pathways and metabolites that may impact fungal development and pathogenicity. As we get closer to solve the primary effects of each ionic liquid family and their specific gene targets, the vision of developing antifungal ionic liquids and/or materials, by taking advantage of elegant progresses in this field, might become a reality. Task designed formulations may improve the performance of conventional antifungal drugs, build functional coatings for reducing allergens production, or aid in the recovery of antifungal plant polymers. The frontier research in this cross disciplinary field may provide us unforeseen means to address the global concern of mycotic diseases. Pathogenic and opportunistic fungi are responsible for numerous infections, killing annually nearly 1.5 million immunocompromised individuals worldwide, a similar rate to malaria or tuberculosis. This perspective will review our major findings and current hypotheses, contextualizing how they might bring us closer to efficient strategies to prevent and fight mycotic diseases. PMID- 26903989 TI - In silico Analysis of HIV-1 Env-gp120 Reveals Structural Bases for Viral Adaptation in Growth-Restrictive Cells. AB - Variable V1/V2 and V3 loops on human immunodeficiency virus type 1 (HIV-1) envelope-gp120 core play key roles in modulating viral competence to recognize two infection receptors, CD4 and chemokine-receptors. However, molecular bases for the modulation largely remain unclear. To address these issues, we constructed structural models for a full-length gp120 in CD4-free and -bound states. The models showed topologies of gp120 surface loop that agree with those in reported structural data. Molecular dynamics simulation showed that in the unliganded state, V1/V2 loop settled into a thermodynamically stable arrangement near V3 loop for conformational masking of V3 tip, a potent neutralization epitope. In the CD4-bound state, however, V1/V2 loop was rearranged near the bound CD4 to support CD4 binding. In parallel, cell-based adaptation in the absence of anti-viral antibody pressures led to the identification of amino acid substitutions that individually enhance viral entry and growth efficiencies in association with reduced sensitivity to CCR5 antagonist TAK-779. Notably, all these substitutions were positioned on the receptors binding surfaces in V1/V2 or V3 loop. In silico structural studies predicted some physical changes of gp120 by substitutions with alterations in viral replication phenotypes. These data suggest that V1/V2 loop is critical for creating a gp120 structure that masks co receptor binding site compatible with maintenance of viral infectivity, and for tuning a functional balance of gp120 between immune escape ability and infectivity to optimize HIV-1 replication fitness. PMID- 26903991 TI - Cetacean Morbillivirus-Associated Pathology: Knowns and Unknowns. AB - The present minireview deals with the pathology of Cetacean Morbillivirus (CeMV) infection in free-ranging cetaceans. In this respect, while "classical" CeMV associated lesions were observed in the lung, brain, and lymphoid tissues from striped dolphins (Stenella coeruleoalba) and pilot whales (Globicephala melas) which were victims of the 1990-1992 and 2006-2008 epidemics in the Western Mediterranean, an apparent reduction in CeMV neurovirulence, along with a different viral antigen's tissue and cell distribution, were found during the 2010-2011 and the 2013 outbreaks in the same area. Of remarkable concern are also the documented CeMV ability to induce maternally acquired infections in wild cetaceans, coupled with the progressively expanding geographic and host range of the virus in both Hemispheres, as well as in conjunction with the intriguing forms of "brain-only" morbilliviral infection increasingly reported in Mediterranean-striped dolphins. Future research in this area should address the virus-host interaction dynamics, with particular emphasis on the cell receptors specifying viral tissue tropism in relation to the different cetacean species and to their susceptibility to infection, as well as to the CeMV strains circulating worldwide. PMID- 26903992 TI - Bioactive Organocopper Compound from Pseudomonas aeruginosa Inhibits the Growth of Xanthomonas citri subsp. citri. AB - Citrus canker is a very destructive disease of citrus species. The challenge is to find new compounds that show strong antibiotic activity and low toxicity to plants and the environment. The objectives of the present study were (1) to extract, purify and evaluate the secondary metabolites with antibiotic activity produced by Pseudomonas aeruginosa LV strain in vitro against Xanthomonas citri subsp. citri (strain 306), (2) to determine the potential of semi-purified secondary metabolites in foliar application to control citrus canker under greenhouse conditions, and (3) to identify antibiotic activity in orange leaf mesophyll infected with strain 306, by electron microscopy. Two pure bioactive compounds were isolated, an organocopper antibiotic compound (OAC) and phenazine 1-carboxamide. Phenazine-1-carboxamide did not show any antibiotic activity under the experimental conditions used in this study. The OAC showed a high level of antibiotic activity with a minimum inhibitory concentration of 0.12 MUg mL(-1). In greenhouse tests for control of citrus canker in orange trees, the semi purified fraction F3d reduced lesion formation by about 97%. The concentration used was 500 times lower than that for the recommended commercial copper-based product. Electron microscopy showed that F3d altered the exopolysaccharide matrix and caused cell lysis of the pathogen inside the citrus canker lesions. These results suggest that secondary metabolites produced by inducing P. aeruginosa LV strain have a high potential to be used as a bioproduct to control citrus canker. PMID- 26903993 TI - Coupling Between Heterotrophic Nanoflagellates and Bacteria in Fresh Waters: Does Latitude Make a Difference? AB - Recent studies reported comparatively lower heterotrophic bacteria (HB) abundances in tropical regions, indicating that factors involved in bacterial losses could be more relevant in the tropics. Heterotrophic nanoflagellates (HNF) are considered the main predators of HB in aquatic ecosystems, and one should expect higher abundances in the tropics because of differences in the food web configuration (absence of large daphnids). However, there are no comprehensive studies comparing HB and HNF abundances in a latitudinal gradient. We hypothesized that HB abundance would be lower in the tropics because HNF abundance would be higher, resulting in a tighter HNF-HB coupling. To test this hypothesis, we compiled a large dataset of HB and HNF abundances from tropical and temperate freshwater environments. We found that both HB and HNF abundances were lower in the tropical region, and that HNF-HB coupling does not differ between temperate and tropical regions. The lower HNF abundance and lack of coupling may be explained by a strong top-down control on HNF and/or their herbivory preference. Besides, no relationship was found between bacterial specific growth rate and either chlorophyll-a and HB abundance, indicating that bacterial losses may have an important role in tropical freshwaters. Thus, we found that HNF is likely not the main controllers of HB abundance, and that grazing by ciliates and cladocerans, together with the physiological effects of higher temperatures, may explain the high bacterial loss rates in the tropics. PMID- 26903994 TI - Editorial: Systems Biology and Ecology of Microbial Mat Communities. PMID- 26903995 TI - Comparison of Fungal Community in Black Pepper-Vanilla and Vanilla Monoculture Systems Associated with Vanilla Fusarium Wilt Disease. AB - Long-term vanilla monocropping often results in the occurrence of vanilla Fusarium wilt disease, seriously affecting its production all over the world. In the present study, vanilla exhibited significantly less Fusarium wilt disease in the soil of a long-term continuously cropped black pepper orchard. The entire fungal communities of bulk and rhizosphere soils between the black pepper-vanilla system (i.e., vanilla cropped in the soil of a continuously cropped black pepper orchard) and vanilla monoculture system were compared through the deep pyrosequencing. The results showed that the black pepper-vanilla system revealed a significantly higher fungal diversity than the vanilla monoculture system in both bulk and rhizosphere soils. The UniFrac-weighted PCoA analysis revealed significant differences in bulk soil fungal community structures between the two cropping systems, and fungal community structures were seriously affected by the vanilla root system. In summary, the black pepper-vanilla system harbored a lower abundance of Fusarium oxysporum in the vanilla rhizosphere soil and increased the putatively plant-beneficial fungal groups such as Trichoderma and Penicillium genus, which could explain the healthy growth of vanilla in the soil of the long term continuously cropped black pepper field. Thus, cropping vanilla in the soil of continuously cropped black pepper fields for maintaining the vanilla industry is executable and meaningful as an agro-ecological system. PMID- 26903996 TI - PATtyFams: Protein Families for the Microbial Genomes in the PATRIC Database. AB - The ability to build accurate protein families is a fundamental operation in bioinformatics that influences comparative analyses, genome annotation, and metabolic modeling. For several years we have been maintaining protein families for all microbial genomes in the PATRIC database (Pathosystems Resource Integration Center, patricbrc.org) in order to drive many of the comparative analysis tools that are available through the PATRIC website. However, due to the burgeoning number of genomes, traditional approaches for generating protein families are becoming prohibitive. In this report, we describe a new approach for generating protein families, which we call PATtyFams. This method uses the k-mer based function assignments available through RAST (Rapid Annotation using Subsystem Technology) to rapidly guide family formation, and then differentiates the function-based groups into families using a Markov Cluster algorithm (MCL). This new approach for generating protein families is rapid, scalable and has properties that are consistent with alignment-based methods. PMID- 26903997 TI - Phylogenetic and Pathotypic Characterization of Newcastle Disease Viruses Circulating in South China and Transmission in Different Birds. AB - Although Newcastle disease virus (NDV) with high pathogenicity has frequently been isolated in poultry in China since 1948, the mode of its transmission among avian species remains largely unknown. Given that various wild bird species have been implicated as sources of transmission, in this study we genotypically and pathotypically characterized 23 NDV isolates collected from chickens, ducks, and pigeons in live bird markets (LBMs) in South China as part of an H7N9 surveillance program during December 2013-February 2014. To simulate the natural transmission of different kinds of animals in LBMs, we selected three representative NDVs-namely, GM, YF18, and GZ289-isolated from different birds to evaluate the pathogenicity and transmission of the indicated viruses in chickens, ducks, and pigeons. Furthermore, to investigate the replication and shedding of NDV in poultry, we inoculated the chickens, ducks, and pigeons with 10(6) EID50 of each virus via intraocular and intranasal routes. Eight hour after infection, the naive contact groups were housed with those inoculated with each of the viruses as a means to monitor contact transmission. Our results indicated that genetically diverse viruses circulate in LBMs in South China's Guangdong Province and that NDV from different birds have different tissue tropisms and host ranges when transmitted in different birds. We therefore propose the continuous epidemiological surveillance of LBMs to support the prevention of the spread of these viruses in different birds, especially chickens, and highlight the need for studies of the virus-host relationship. PMID- 26903998 TI - Transcriptional Regulation of Carbohydrate Utilization Pathways in the Bifidobacterium Genus. AB - Bifidobacteria, which represent common commensals of mammalian gut, are believed to have positive effects on human health. The influence of certain non-digestible carbohydrates (and their use as so-called prebiotics) on growth and metabolic activity of bifidobacteria is of increasing interest; however, mechanisms of transcriptional control of carbohydrate metabolism are poorly understood in these species. We used a comparative genomics approach to reconstruct carbohydrate utilization pathways and transcriptional regulons in 10 Bifidobacterium genomes. Analysis of regulatory gene regions revealed candidate DNA motifs and reconstructed regulons for 268 transcription factors from the LacI, ROK, DeoR, AraC, GntR, and TetR families that form 64 orthologous groups of regulators. Most of the reconstructed regulons are local and control specific catabolic pathways for host- and diet-derived glycans and monosaccharides. Mosaic distributions of many of these local regulators across Bifidobacterium species correlate with distribution of corresponding catabolic pathways. In contrast, the maltose, galactose, sucrose, and fructose regulons, as well as a novel global LacI-family regulator that is predicted to control the central carbohydrate metabolism and arabinose catabolism genes, are universally present in all 10 studied bifidobacteria. A novel group of TetR-family regulators presumably controls the glucoside and galactoside utilization pathways. Paralogs of the ribose repressor RbsR control the pyrimidine nucleoside utilization genes. Multiple paralogs of the maltose regulator MalR co-regulate large sets of genes involved in maltodextrin utilization. The inferred metabolic regulons provide new insights on diverse carbohydrate utilization networks in bifidobacteria that can be employed in metabolic modeling, phenotype prediction and the rational development of novel prebiotics. PMID- 26903999 TI - JNK1 Derived from Orange-Spotted Grouper, Epinephelus coioides, Involving in the Evasion and Infection of Singapore Grouper Iridovirus (SGIV). AB - c-Jun N-terminal kinase (JNK) regulates cellular responses to various extracellular stimuli, environmental stresses, pathogen infections, and apoptotic agents. Here, a JNK1, Ec-JNK1, was identified from orange-spotted grouper, Epinephelus coioides. Ec-JNK1 has been found involving in the immune response to pathogen challenges in vivo, and the infection of Singapore grouper iridovirus (SGIV) and SGIV-induced apoptosis in vitro. SGIV infection activated Ec-JNK1, of which phosphorylation of motif TPY is crucial for its activity. Over-expressing Ec-JNK1 phosphorylated transcription factors c-Jun and promoted the infection and replication of SGIV, while partial inhibition of the phosphorylation of Ec-JNK1 showed the opposite effects by over-expressing the dominant-negative EcJNK1 Delta183-185 mutant. Interestingly, SGIV enhanced the viral infectivity by activating Ec-JNK1 which in turn drastically inhibited the antiviral responses of type 1 IFN, indicating that Ec-JNK1 could be involved in blocking IFN signaling during SGIV infection. In addition, Ec-JNK1 enhanced the activation of AP-1, p53, and NF-kappaB, and resulted in increasing the levels of SGIV-induced cell death. The caspase 3-dependent activation correlated with the phosphorylation of Ec-JNK1 and contributed to SGIV-induced apoptosis. Taken together, SGIV modulated the phosphorylation of Ec-JNK1 to inactivate the antiviral signaling, enhance the SGIV-induced apoptosis and activate transcription factors for efficient infection and replication. The "positive cooperativity" molecular mechanism mediated by Ec JNK1 contributes to the successful evasion and infection of iridovirus pathogenesis. PMID- 26904002 TI - The Aeromonas salmonicida Lipopolysaccharide Core from Different Subspecies: The Unusual subsp. pectinolytica. AB - Initial hydridization tests using Aeromonas salmonicida typical and atypical strains showed the possibility of different lipopolysaccharide (LPS) outer cores among these strains. By chemical structural analysis, LPS-core SDS-PAGE gel migration, and functional and comparative genomics we demonstrated that typical A. salmonicida (subsp. salmonicida) strains and atypical subsp. masoucida and probably smithia strains showed the same LPS outer core. A. salmonicida subsp. achromogenes strains show a similar LPS outer core but lack one of the most external residues (a galactose linked alpha1-6 to heptose), not affecting the O antigen LPS linkage. A. salmonicida subsp. pectinolytica strains show a rather changed LPS outer core, which is identical to the LPS outer core from the majority of the A. hydrophila strains studied by genomic analyses. The LPS inner core in all tested A. salmonicida strains, typical and atypical, is well conserved. Furthermore, the LPS inner core seems to be conserved in all the Aeromonas (psychrophilic or mesophilic) strains studied by genomic analyses. PMID- 26904001 TI - Eukaryotic-Type Ser/Thr Protein Kinase Mediated Phosphorylation of Mycobacterial Phosphodiesterase Affects its Localization to the Cell Wall. AB - Phosphodiesterase enzymes, involved in cAMP hydrolysis reaction, are present throughout phylogeny and their phosphorylation mediated regulation remains elusive in prokaryotes. In this context, we focused on this enzyme from Mycobacterium tuberculosis. The gene encoded by Rv0805 was PCR amplified and expressed as a histidine-tagged protein (mPDE) utilizing Escherichia coli based expression system. In kinase assays, upon incubation with mycobacterial Clade I eukaryotic-type Ser/Thr kinases (PknA, PknB, and PknL), Ni-NTA purified mPDE protein exhibited transphosphorylation ability albeit with varying degree. When mPDE was co-expressed one at a time with these kinases in E. coli, it was also recognized by an anti-phosphothreonine antibody, which further indicates its phosphorylating ability. Mass spectrometric analysis identified Thr-309 of mPDE as a phosphosite. In concordance with this observation, anti-phosphothreonine antibody marginally recognized mPDE-T309A mutant protein; however, such alteration did not affect the enzymatic activity. Interestingly, mPDE expressed in Mycobacterium smegmatis yielded a phosphorylated protein that preferentially localized to cell wall. In contrast, mPDE-T309A, the phosphoablative variant of mPDE, did not show such behavior. On the other hand, phosphomimics of mPDE (T309D or T309E), exhibited similar cell wall anchorage as was observed with the wild type. Thus, our results provide credence to the fact that eukaryotic-type Ser/Thr kinase mediated phosphorylation of mPDE renders negative charge to the protein, promoting its localization on cell wall. Furthermore, multiple sequence alignment revealed that Thr-309 is conserved among mPDE orthologs of M. tuberculosis complex, which presumably emphasizes evolutionary significance of phosphorylation at this residue. PMID- 26904000 TI - New Bio-Indicators for Long Term Natural Attenuation of Monoaromatic Compounds in Deep Terrestrial Aquifers. AB - Deep subsurface aquifers despite difficult access, represent important water resources and, at the same time, are key locations for subsurface engineering activities for the oil and gas industries, geothermal energy, and CO2 or energy storage. Formation water originating from a 760 m-deep geological gas storage aquifer was sampled and microcosms were set up to test the biodegradation potential of BTEX by indigenous microorganisms. The microbial community diversity was studied using molecular approaches based on 16S rRNA genes. After a long incubation period, with several subcultures, a sulfate-reducing consortium composed of only two Desulfotomaculum populations was observed able to degrade benzene, toluene, and ethylbenzene, extending the number of hydrocarbonoclastic related species among the Desulfotomaculum genus. Furthermore, we were able to couple specific carbon and hydrogen isotopic fractionation during benzene removal and the results obtained by dual compound specific isotope analysis (??C = 2.40/00 +/- 0.30/00; ??H = -570/00 +/- 0.980/00; AKIEC: 1.0146 +/- 0.0009, and AKIEH: 1.5184 +/- 0.0283) were close to those obtained previously in sulfate reducing conditions: this finding could confirm the existence of a common enzymatic reaction involving sulfate-reducers to activate benzene anaerobically. Although we cannot assign the role of each population of Desulfotomaculum in the mono-aromatic hydrocarbon degradation, this study suggests an important role of the genus Desulfotomaculum as potential biodegrader among indigenous populations in subsurface habitats. This community represents the simplest model of benzene degrading anaerobes originating from the deepest subterranean settings ever described. As Desulfotomaculum species are often encountered in subsurface environments, this study provides some interesting results for assessing the natural response of these specific hydrologic systems in response to BTEX contamination during remediation projects. PMID- 26904003 TI - Genome Sequence Analysis of CsRV1: A Pathogenic Reovirus that Infects the Blue Crab Callinectes sapidus Across Its Trans-Hemispheric Range. AB - The blue crab, Callinectes sapidus Rathbun, 1896, which is a commercially important trophic link in coastal ecosystems of the western Atlantic, is infected in both North and South America by C. sapidus Reovirus 1 (CsRV1), a double stranded RNA virus. The 12 genome segments of a North American strain of CsRV1 were sequenced using Ion Torrent technology. Putative functions could be assigned for 3 of the 13 proteins encoded in the genome, based on their similarity to proteins encoded in other reovirus genomes. Comparison of the CsRV1 RNA-dependent RNA polymerase (RdRP) sequence to genomes of other crab-infecting reoviruses shows that it is similar to the mud crab reovirus found in Scylla serrata and WX 2012 in Eriocheir sinensis, Chinese mitten crab, and supports the idea that there is a distinct "Crabreo" genus, different from Seadornavirus and Cardoreovirus, the two closest genera in the Reoviridae. A region of 98% nucleotide sequence identity between CsRV1 and the only available sequence of the P virus of Macropipus depurator suggests that these two viruses may be closely related. An 860 nucleotide region of the CsRV1 RdRP gene was amplified and sequenced from 15 infected crabs collected from across the geographic range of C. sapidus. Pairwise analysis of predicted protein sequences shows that CsRV1 strains in Brazil can be distinguished from those in North America based on conserved residues in this gene. The sequencing, annotation, and preliminary population metrics of the genome of CsRV1 should facilitate additional studies in diverse disciplines, including structure-function relationships of reovirus proteins, investigations into the evolution of the Reoviridae, and biogeographic research on the connectivity of C. sapidus populations across the Northern and Southern hemispheres. PMID- 26904005 TI - High Molecular Weight Barley beta-Glucan Alters Gut Microbiota Toward Reduced Cardiovascular Disease Risk. AB - The physiological cholesterol-lowering benefits of beta-glucan have been well documented, however, whether modulation of gut microbiota by beta-glucan is associated with these physiological effects remains unknown. The objectives of this study were therefore to determine the impact of beta-glucan on the composition of gut microbiota in mildly hypercholesterolemic individuals and to identify if the altered microbiota are associated with bioactivity of beta-glucan in improving risk factors of cardiovascular disease (CVD). Using a randomized, controlled crossover study design, individuals received for 5-week either a treatment breakfast containing 3 g high molecular weight (HMW), 3 g low molecular weight (LMW), 5 g LMW barley beta-glucan, or wheat and rice. The American Heart Association (AHA) diet served as the background diet for all treatment groups. Phases were separated by 4-week washout periods. Fecal samples were collected at the end of each intervention phase and subjected to Illumina sequencing of 16S rRNA genes. Results revealed that at the phylum level, supplementation of 3 g/d HMW beta-glucan increased Bacteroidetes and decreased Firmicutes abundances compared to control (P < 0.001). At the genus level, consumption of 3 g/d HMW beta-glucan increased Bacteroides (P < 0.003), tended to increase Prevotella (P < 0.1) but decreased Dorea (P < 0.1), whereas diets containing 5 g LMW beta-glucan and 3 g LMW beta-glucan failed to alter the gut microbiota composition. Bacteroides, Prevotella, and Dorea composition correlated (P < 0.05) with shifts of CVD risk factors, including body mass index, waist circumference, blood pressure, as well as triglyceride levels. Our data suggest that consumption of HMW beta-glucan favorably alters the composition of gut microbiota and this altered microbiota profile associates with a reduction of CVD risk markers. Together, our study suggests that beta-glucan induced shifts in gut microbiota in a MW-dependent manner and that might be one of the underlying mechanisms responsible for the physiological benefits of beta-glucan. PMID- 26904004 TI - Genomic Analysis of the Human Gut Microbiome Suggests Novel Enzymes Involved in Quinone Biosynthesis. AB - Ubiquinone and menaquinone are membrane lipid-soluble carriers of electrons that are essential for cellular respiration. Eukaryotic cells can synthesize ubiquinone but not menaquinone, whereas prokaryotes can synthesize both quinones. So far, most of the human gut microbiome (HGM) studies have been based on metagenomic analysis. Here, we applied an analysis of individual HGM genomes to the identification of ubiquinone and menaquinone biosynthetic pathways. In our opinion, the shift from metagenomics to analysis of individual genomes is a pivotal milestone in investigation of bacterial communities, including the HGM. The key results of this study are as follows. (i) The distribution of the canonical pathways in the HGM genomes was consistent with previous reports and with the distribution of the quinone-dependent reductases for electron acceptors. (ii) The comparative genomics analysis identified four alternative forms of the previously known enzymes for quinone biosynthesis. (iii) Genes for the previously unknown part of the futalosine pathway were identified, and the corresponding biochemical reactions were proposed. We discuss the remaining gaps in the menaquinone and ubiquinone pathways in some of the microbes, which indicate the existence of further alternate genes or routes. Together, these findings provide further insight into the biosynthesis of quinones in bacteria and the physiology of the HGM. PMID- 26904006 TI - Diversity and Dynamics of Active Small Microbial Eukaryotes in the Anoxic Zone of a Freshwater Meromictic Lake (Pavin, France). AB - Microbial eukaryotes play a crucial role in ecosystem functioning and oxygen is considered to be one of the strongest barriers against their local dispersal. However, diversity of microbial eukaryotes in freshwater habitats with oxygen gradients has previously received very little attention. We applied high throughput sequencing (V4 region of the 18S rRNA gene) in conjunction with quantitative PCR (DNA and RNA) and fluorescent in situ hybridization (FISH) analyses, to provide an unique spatio-temporal analysis of microbial eukaryotes diversity and potential activity in a meromictic freshwater lake (lake Pavin). This study revealed a high genetic diversity of unicellular eukaryotes in the permanent anoxic zone of lake Pavin and allowed the discrimination of active vs. inactive components. Forty-two percent of the OTUs (Operational Taxonomic Units) are exclusively present in the monimolimnion, where Alveolata (Ciliophora and Dinophyceae) and Fungi (Dikarya and Chytrids) are the most active phyla and are probably represented by species capable of anaerobic metabolism. Pigmented eukaryotes (Haptophyceae and Chlorophyceae) are also present and active in this zone, which opens up questions regarding their metabolism. PMID- 26904007 TI - Quorum Sensing: An Under-Explored Phenomenon in the Phylum Actinobacteria. AB - Quorum sensing is known to play a major role in the regulation of secondary metabolite production, especially, antibiotics, and morphogenesis in the phylum Actinobacteria. Although it is one of the largest bacterial phylum, only 25 of the 342 genera have been reported to use quorum sensing. Of these, only nine have accompanying experimental evidence; the rest are only known through bioinformatic analysis of gene/genome sequences. It is evident that this important communication mechanism is not extensively explored in Actinobacteria. In this review, we summarize the different quorum sensing systems while identifying the limitations of the existing screening strategies and addressing the improvements that have taken place in this field in recent years. The gamma-butyrolactone system turned out to be almost exclusively limited to this phylum. In addition, methylenomycin furans, AI-2 and other putative AHL-like signaling molecules are also reported in Actinobacteria. The lack of existing screening systems in detecting minute quantities and of a wider range of signaling molecules was a major reason behind the limited information available on quorum sensing in this phylum. However, recent improvements in screening strategies hold a promising future and are likely to increase the discovery of new signaling molecules. Further, the quorum quenching ability in many Actinobacteria has a great potential in controlling the spread of plant and animal pathogens. A systematic and coordinated effort is required to screen and exploit the enormous potential that quorum sensing in the phylum Actinobacteria has to offer for human benefit. PMID- 26904008 TI - Nitrate and Inhibition of Ruminal Methanogenesis: Microbial Ecology, Obstacles, and Opportunities for Lowering Methane Emissions from Ruminant Livestock. AB - Ruminal methane production is among the main targets for greenhouse gas (GHG) mitigation for the animal agriculture industry. Many compounds have been evaluated for their efficacy to suppress enteric methane production by ruminal microorganisms. Of these, nitrate as an alternative hydrogen sink has been among the most promising, but it suffers from variability in efficacy for reasons that are not understood. The accumulation of nitrite, which is poisonous when absorbed into the animal's circulation, is also variable and poorly understood. This review identifies large gaps in our knowledge of rumen microbial ecology that handicap the further development and safety of nitrate as a dietary additive. Three main bacterial species have been associated historically with ruminal nitrate reduction, namely Wolinella succinogenes, Veillonella parvula, and Selenomonas ruminantium, but others almost certainly exist in the largely uncultivated ruminal microbiota. Indications are strong that ciliate protozoa can reduce nitrate, but the significance of their role relative to bacteria is not known. The metabolic fate of the reduced nitrate has not been studied in detail. It is important to be sure that nitrate metabolism and efforts to enhance rates of nitrite reduction do not lead to the evolution of the much more potent GHG, nitrous oxide. The relative importance of direct inhibition of archaeal methanogenic enzymes by nitrite or the efficiency of capture of hydrogen by nitrate reduction in lowering methane production is also not known, nor are nitrite effects on other members of the microbiota. How effective would combining mitigation methods be, based on our understanding of the effects of nitrate and nitrite on the microbiome? Answering these fundamental microbiological questions is essential in assessing the potential of dietary nitrate to limit methane emissions from ruminant livestock. PMID- 26904009 TI - Sub-Lethal Dose of Shiga Toxin 2 from Enterohemorrhagic Escherichia coli Affects Balance and Cerebellar Cytoarchitecture. AB - Shiga toxin producing Escherichia coli may damage the central nervous system before or concomitantly to manifested hemolytic-uremic syndrome symptoms. The cerebellum is frequently damaged during this syndrome, however, the deleterious effects of Shiga toxin 2 has never been integrally reported by ultrastructural, physiological and behavioral means. The aim of this study was to determine the cerebellar compromise after intravenous administration of a sub-lethal dose of Shiga toxin 2 by measuring the cerebellar blood-brain barrier permeability, behavioral task of cerebellar functionality (inclined plane test), and ultrastructural analysis (transmission electron microscope). Intravenous administration of vehicle (control group), sub-lethal dose of 0.5 and 1 etag of Stx2 per mouse were tested for behavioral and ultrastructural studies. A set of three independent experiments were performed for each study (n = 6). Blood-brain barrier resulted damaged and consequently its permeability was significantly increased. Lower scores obtained in the inclined plane task denoted poor cerebellar functionality in comparison to their controls. The most significant lower score was obtained after 5 days of 1 etag of toxin administration. Transmission electron microscope micrographs from the Stx2-treated groups showed neurons with a progressive neurodegenerative condition in a dose dependent manner. As sub-lethal intravenous Shiga toxin 2 altered the blood brain barrier permeability in the cerebellum the toxin penetrated the cerebellar parenchyma and produced cell damaged with significant functional implications in the test balance. PMID- 26904010 TI - Diversity, Abundance, and Niche Differentiation of Ammonia-Oxidizing Prokaryotes in Mud Deposits of the Eastern China Marginal Seas. AB - The eastern China marginal seas (ECMS) are prominent examples of river-dominated ocean margins, whose most characteristic feature is the existence of isolated mud patches on sandy sediments. Ammonia-oxidizing prokaryotes play a crucial role in the nitrogen cycles of many marine environments, including marginal seas. However, few studies have attempted to address the distribution patterns of ammonia-oxidizing prokaryotes in mud deposits of these seas. The horizontal and vertical community composition and abundance of ammonia-oxidizing archaea (AOA) and bacteria (AOB) were investigated in mud deposits of the South Yellow Sea (SYS) and the East China Sea (ECS) by using amoA clone libraries and quantitative PCR. The diversity of AOB was comparable or higher in the mud zone of SYS and lower in ECS when compared with AOA. Vertically, surface sediments had generally higher diversity of AOA and AOB than middle and bottom layers. Diversity of AOA and AOB showed significant correlation with latitude. Nitrosopumilus and Nitrosospira lineages dominated AOA and AOB communities, respectively. Both AOA and AOB assemblages exhibited greater variations across different sites than those among various depths at one site. The abundance of bacterial amoA was generally higher than that of archaeal amoA, and both of them decreased with depth. Niche differentiation, which was affected by dissolved oxygen, salinity, ammonia, and silicate (SiO[Formula: see text]), was observed between AOA and AOB and among different groups of them. The spatial distribution of AOA and AOB was significantly correlated with delta(15)NTN and SiO[Formula: see text], and nitrate and delta(13)C, respectively. Both archaeal and bacterial amoA abundance correlated strongly with SiO[Formula: see text]. This study improves our understanding of spatial distribution of AOA and AOB in ecosystems featuring oceanic mud deposits. PMID- 26904011 TI - Reduced Binding of the Endolysin LysTP712 to Lactococcus lactis DeltaftsH Contributes to Phage Resistance. AB - Absence of the membrane protease FtsH in Lactococcus lactis hinders release of the bacteriophage TP712. In this work we have analyzed the mechanism responsible for the non-lytic phenotype of L. lactis DeltaftsH after phage infection. The lytic cassette of TP712 contains a putative antiholin-pinholin system and a modular endolysin (LysTP712). Inducible expression of the holin gene demonstrated the presence of a dual start motif which is functional in both wildtype and L. lactis DeltaftsH cells. Moreover, simulating holin activity with ionophores accelerated lysis of wildtype cells but not L. lactis DeltaftsH cells, suggesting inhibition of the endolysin rather than a role of FtsH in holin activation. However, zymograms revealed the synthesis of an active endolysin in both wildtype and L. lactis DeltaftsH TP712 lysogens. A reporter protein was generated by fusing the cell wall binding domain of LysTP712 to the fluorescent mCherry protein. Binding of this reporter protein took place at the septa of both wildtype and L. lactis DeltaftsH cells as shown by fluorescence microscopy. Nonetheless, fluorescence spectroscopy demonstrated that mutant cells bound 40% less protein. In conclusion, the non-lytic phenotype of L. lactis DeltaftsH is not due to direct action of the FtsH protease on the phage lytic proteins but rather to a putative function of FtsH in modulating the architecture of the L. lactis cell envelope that results in a lower affinity of the phage endolysin to its substrate. PMID- 26904012 TI - Presence of Viral RNA and Proteins in Exosomes from Cellular Clones Resistant to Rift Valley Fever Virus Infection. AB - Rift Valley Fever Virus (RVFV) is a RNA virus that belongs to the genus Phlebovirus, family Bunyaviridae. It infects humans and livestock and causes Rift Valley fever. RVFV is considered an agricultural pathogen by the USDA, as it can cause up to 100% abortion in cattle and extensive death of newborns. In addition, it is designated as Category A pathogen by the CDC and the NIAID. In some human cases of RVFV infection, the virus causes fever, ocular damage, liver damage, hemorrhagic fever, and death. There are currently limited options for vaccine candidates, which include the MP-12 and clone 13 versions of RVFV. Viral infections often deregulate multiple cellular pathways that contribute to replication and host pathology. We have previously shown that latent human immunodeficiency virus-1 (HIV-1) and human T-cell lymphotropic virus-1 (HTLV-1) infected cells secrete exosomes that contain short viral RNAs, limited number of genomic RNAs, and viral proteins. These exosomes largely target neighboring cells and activate the NF-kappaB pathway, leading to cell proliferation, and overall better viral replication. In this manuscript, we studied the effects of exosome formation from RVFV infected cells and their function on recipient cells. We initially infected cells, isolated resistant clones, and further purified using dilution cloning. We then characterized these cells as resistant to new RVFV infection, but sensitive to other viral infections, including Venezuelan Equine Encephalitis Virus (VEEV). These clones contained normal markers (i.e., CD63) for exosomes and were able to activate the TLR pathway in recipient reporter cells. Interestingly, the exosome rich preparations, much like their host cell, contained viral RNA (L, M, and S genome). The RNAs were detected using qRT-PCR in both parental and exosomal preparations as well as in CD63 immunoprecipitates. Viral proteins such as N and a modified form of NSs were present in some of these exosomes. Finally, treatment of recipient cells (T-cells and monocytic cells) showed drastic rate of apoptosis through PARP cleavage and caspase 3 activation from some but not all exosome enriched preparations. Collectively, these data suggest that exosomes from RVFV infected cells alter the dynamics of the immune cells and may contribute to pathology of the viral infection. PMID- 26904013 TI - Thiazolidinedione-8 Alters Symbiotic Relationship in C. albicans-S. mutans Dual Species Biofilm. AB - The small molecule, thiazolidinedione-8 (S-8) was shown to impair biofilm formation of various microbial pathogens, including the fungus Candida albicans and Streptococcus mutans. Previously, we have evaluated the specific molecular mode of S-8 action against C. albicans biofilm-associated pathogenicity. In this study we investigated the influence of S-8 on dual species, C. albicans-S. mutans biofilm. We show that in the presence of S-8 a reduction of the co-species biofilm formation occurred with a major effect on C. albicans. Biofilm biomass and exopolysaccharide (EPS) production were significantly reduced by S-8. Moreover, the agent caused oxidative stress associated with a strong induction of reactive oxygen species and hydrogen peroxide uptake inhibition by a mixed biofilm. In addition, S-8 altered symbiotic relationship between these species by a complex mechanism. Streptococcal genes associated with quorum sensing (QS) (comDE and luxS), EPS production (gtfBCD and gbpB), as well as genes related to protection against oxidative stress (nox and sodA) were markedly upregulated by S 8. In contrast, fungal genes related to hyphae formation (hwp1), adhesion (als3), hydrophobicity (csh1), and oxidative stress response (sod1, sod2, and cat1) were downregulated in the presence of S-8. In addition, ywp1 gene associated with yeast form of C. albicans was induced by S-8, which is correlated with appearance of mostly yeast cells in S-8 treated dual species biofilms. We concluded that S-8 disturbs symbiotic balance between C. albicans and S. mutans in dual species biofilm. PMID- 26904015 TI - Multiple ESBL-Producing Escherichia coli Sequence Types Carrying Quinolone and Aminoglycoside Resistance Genes Circulating in Companion and Domestic Farm Animals in Mwanza, Tanzania, Harbor Commonly Occurring Plasmids. AB - The increased presence of extended-spectrum beta-lactamase (ESBL)-producing bacteria in humans, animals, and their surrounding environments is of global concern. Currently there is limited information on ESBL presence in rural farming communities worldwide. We performed a cross-sectional study in Mwanza, Tanzania, involving 600 companion and domestic farm animals between August/September 2014. Rectal swab/cloaca specimens were processed to identify ESBL-producing Enterobacteriaceae. We detected 130 (21.7%) animals carrying ESBL-producing bacteria, the highest carriage being among dogs and pigs [39.2% (51/130) and 33.1% (43/130), respectively]. The majority of isolates were Escherichia coli [93.3% (125/134)] and exotic breed type [OR (95%CI) = 2.372 (1.460-3.854), p value < 0.001] was found to be a predictor of ESBL carriage among animals. Whole genome sequences of 25 ESBL-producing E. coli were analyzed for phylogenetic relationships using multi-locus sequence typing (MLST) and core genome comparisons. Fourteen different sequence types were detected of which ST617 (7/25), ST2852 (3/25), ST1303 (3/25) were the most abundant. All isolates harbored the bla CTX-M-15 allele, 22/25 carried strA and strB, 12/25 aac(6')-lb cr, and 11/25 qnrS1. Antibiotic resistance was associated with IncF, IncY, as well as non-typable plasmids. Eleven isolates carried pPGRT46-related plasmids, previously reported from isolates in Nigeria. Five isolates had plasmids exhibiting 85-99% homology to pCA28, previously detected in isolates from the US. Our findings indicate a pan-species distribution of ESBL-producing E. coli clonal groups in farming communities and provide evidence for plasmids harboring antibiotic resistances of regional and international impact. PMID- 26904014 TI - Mass Spectrometry Offers Insight into the Role of Ser/Thr/Tyr Phosphorylation in the Mycobacteria. AB - Phosphorylation is a post translational modification which can rapidly regulate biochemical pathways by altering protein function, and has been associated with pathogenicity in bacteria. Once engulfed by host macrophages, pathogenic bacteria are exposed to harsh conditions and must respond rapidly in order to survive. The causative agent of TB, Mycobacterium tuberculosis, is unusual amongst the bacteria because it can survive within the host macrophage for decades in a latent state, demonstrating a remarkable capacity to successfully evade the host immune response. This ability may be mediated in part by regulatory mechanisms such as ser/thr/tyr phosphorylation. Mass spectrometry-based proteomics has afforded us the capacity to identify hundreds of phosphorylation sites in the bacterial proteome, allowing for comparative phosphoproteomic studies in the mycobacteria. There remains an urgent need to validate the reported phosphosites, and to elucidate their biological function in the context of pathogenicity. However, given the sheer number of putative phosphorylation events in the mycobacterial proteome, and the technical difficulty of assigning biological function to a phosphorylation event, it will not be trivial to do so. There are currently six published phosphoproteomic investigations of a member of mycobacteria. Here, we combine the datasets from these studies in order to identify commonly detected phosphopeptides and phosphosites in order to present high confidence candidates for further validation. By applying modern mass spectrometry-based techniques to improve our understanding of phosphorylation and other PTMs in pathogenic bacteria, we may identify candidates for therapeutic intervention. PMID- 26904016 TI - Improved Environmental Genomes via Integration of Metagenomic and Single-Cell Assemblies. AB - Assembling complete or near complete genomes from complex microbial communities remains a significant challenge in metagenomic studies. Recent developments in single cell amplified genomes (SAGs) have enabled the sequencing of individual draft genomes representative of uncultivated microbial populations. SAGs suffer from incomplete and uneven coverage due to artifacts that arise from multiple displacement amplification techniques. Conversely, metagenomic sequence data does not suffer from the same biases as SAGs, and significant improvements have been realized in the recovery of draft genomes from metagenomes. Nevertheless, the inherent genomic complexity of many microbial communities often obfuscates facile generation of population genome assemblies from metagenomic data. Here we describe a new method for metagenomic-guided SAG assembly that leverages the advantages of both methods and significantly improves the completeness of initial SAGs assemblies. We demonstrate that SAG assemblies of two cosmopolitan marine lineages-Marine Group 1 Thaumarchaeota and SAR324 clade bacterioplankton-were substantially improved using this approach. Moreover, the improved assemblies strengthened biological inferences. For example, the improved SAR324 clade genome assembly revealed the presence of many genes in phenylalanine catabolism and flagellar assembly that were absent in the original SAG. PMID- 26904017 TI - Extraintestinal Infections Caused by Non-toxigenic Vibrio cholerae non-O1/non O139. AB - Vibrio cholerae is an aerobic, sucrose fermentative Gram-negative bacterium that generally prevails in the environment. Pathogenic V. cholerae is well-known as causative agent of acute diarrhea. Apart from enteric infections, V. cholerae may also cause other diseases. However, their role in causing extraintestinal infections is not fully known as it needs proper identification and evaluation. Four cases of extraintestinal infections due to V. cholerae non-O1/non-O139 have been investigated. The isolates were screened for phenotypic and genetic characteristics with reference to their major virulence genes. Serologically distinct isolates harbored rtx, msh, and hly but lacked enteric toxin encoding genes that are generally present in toxigenic V. cholerae. Timely detection of this organism can prevent fatalities in hospital settings. The underlying virulence potential of V. cholerae needs appropriate testing and intervention. PMID- 26904018 TI - Exposure of E. coli to DNA-Methylating Agents Impairs Biofilm Formation and Invasion of Eukaryotic Cells via Down Regulation of the N-Acetylneuraminate Lyase NanA. AB - DNA methylation damage can be induced by endogenous and exogenous chemical agents, which has led every living organism to develop suitable response strategies. We investigated protein expression profiles of Escherichia coli upon exposure to the alkylating agent methyl-methane sulfonate (MMS) by differential proteomics. Quantitative proteomic data showed a massive downregulation of enzymes belonging to the glycolytic pathway and fatty acids degradation, strongly suggesting a decrease of energy production. A strong reduction in the expression of the N-acetylneuraminate lyases (NanA) involved in the sialic acid metabolism was also observed. Using a null NanA mutant and DANA, a substrate analog acting as competitive inhibitor, we demonstrated that down regulation of NanA affects biofilm formation and adhesion properties of E. coli MV1161. Exposure to alkylating agents also decreased biofilm formation and bacterial adhesion to Caco 2 eukaryotic cell line by the adherent invasive E. coli (AIEC) strain LF82. Our data showed that methylation stress impairs E. coli adhesion properties and suggest a possible role of NanA in biofilm formation and bacteria host interactions. PMID- 26904019 TI - 16S-23S rRNA Gene Intergenic Spacer Region Variability Helps Resolve Closely Related Sphingomonads. AB - Sphingomonads comprise a physiologically versatile group many of which appear to be adapted to oligotrophic environments, but several also had features in their genomes indicative of host associations. In this study, the extent variability of the 16S-23S rDNA intergenic spacer (ITS) sequences of 14 ATCC reference sphingomonad strains and 23 isolates recovered from drinking water was investigated through PCR amplification and sequencing. Sequencing analysis of the 16S-23S rRNA gene ITS region revealed that the ITS sizes for all studied isolates varied between 415 and 849 bp, while their G+C content was 42.2-57.9 mol%. Five distinct ITS types were identified: ITS(none) (without tRNA genes), ITS(Ala(TGC)), ITS(Ala(TGC)+Ile(GAT)), ITS(Ile(GAT)+Ala(TGC)), and ITS (Ile(GAT)+Pseudo). All of the identified tRNA(Ala(TGC)) molecules consisted of 73 bases, and all of the tRNA(Ile(GAT)) molecules consisted of 74 bases. We also detected striking variability in the size of the ITS region among the various examined isolates. Highest variability was detected within the ITS-2. The importance of this study is that this is the first comparison of the 16S-23S rDNA ITS sequence similarities and tRNA genes from sphingomonads. Collectively the data obtained in this study revealed the heterogeneity and extent of variability within the ITS region compared to the 16S rRNA gene within closely related isolates. Sequence and length polymorphisms within the ITS region along with the ITS types (tRNA-containing or lacking and the type of tRNA) and ITS-2 size and sequence similarities allowed us to overcome the limitation we previously encountered in resolving closely related isolates based on the 16S rRNA gene sequence. PMID- 26904020 TI - The Cacti Microbiome: Interplay between Habitat-Filtering and Host-Specificity. AB - Cactaceae represents one of the most species-rich families of succulent plants native to arid and semi-arid ecosystems, yet the associations Cacti establish with microorganisms and the rules governing microbial community assembly remain poorly understood. We analyzed the composition, diversity, and factors influencing above- and below-ground bacterial, archaeal, and fungal communities associated with two native and sympatric Cacti species: Myrtillocactus geometrizans and Opuntia robusta. Phylogenetic profiling showed that the composition and assembly of microbial communities associated with Cacti were primarily influenced by the plant compartment; plant species, site, and season played only a minor role. Remarkably, bacterial, and archaeal diversity was higher in the phyllosphere than in the rhizosphere of Cacti, while the opposite was true for fungi. Semi-arid soils exhibited the highest levels of microbial diversity whereas the stem endosphere the lowest. Despite their taxonomic distance, M. geometrizans and O. robusta shared most microbial taxa in all analyzed compartments. Influence of the plant host did only play a larger role in the fungal communities of the stem endosphere. These results suggest that fungi establish specific interactions with their host plant inside the stem, whereas microbial communities in the other plant compartments may play similar functional roles in these two species. Biochemical and molecular characterization of seed borne bacteria of Cacti supports the idea that these microbial symbionts may be vertically inherited and could promote plant growth and drought tolerance for the fitness of the Cacti holobiont. We envision this knowledge will help improve and sustain agriculture in arid and semi-arid regions of the world. PMID- 26904021 TI - Immunoprotective Efficacy of Acinetobacter baumannii Outer Membrane Protein, FilF, Predicted In silico as a Potential Vaccine Candidate. AB - Acinetobacter baumannii is emerging as a serious nosocomial pathogen with multidrug resistance that has made it difficult to cure and development of efficacious treatment against this pathogen is direly needed. This has led to investigate vaccine approach to prevent and treat A. baumannii infections. In this work, an outer membrane putative pilus assembly protein, FilF, was predicted as vaccine candidate by in silico analysis of A. baumannii proteome and was found to be conserved among the A. baumannii strains. It was cloned and expressed in E. coli BL21(DE3) and purified by Ni-NTA chromatography. Immunization with FilF generated high antibody titer (>64,000) and provided 50% protection against a standardized lethal dose (10(8) CFU) of A. baumannii in murine pneumonia model. FilF immunization reduced the bacterial load in lungs by 2 and 4 log cycles, 12 and 24 h post infection as compared to adjuvant control; reduced the levels of pro-inflammatory cytokines TNF-alpha, IL-6, IL-33, IFN-gamma, and IL-1beta significantly and histology of lung tissue supported the data by showing considerably reduced damage and infiltration of neutrophils in lungs. These results demonstrate the in vivo validation of immunoprotective efficacy of a protein predicted as a vaccine candidate by in silico proteomic analysis and open the possibilities for exploration of a large array of uncharacterized proteins. PMID- 26904023 TI - Starved and Asphyxiated: How Can CD8(+) T Cells within a Tumor Microenvironment Prevent Tumor Progression. AB - Although cancer immunotherapy has achieved significant breakthroughs in recent years, its overall efficacy remains limited in the majority of patients. One major barrier is exhaustion of tumor antigen-specific CD8(+) tumor-infiltrating lymphocytes (TILs), which conventionally has been attributed to persistent stimulation with antigen within the tumor microenvironment (TME). A series of recent studies have highlighted that the TME poses significant metabolic challenges to TILs, which may contribute to their functional exhaustion. Hypoxia increases the expression of coinhibitors on activated CD8(+) T cells, which in general reduces the T cells' effector functions. It also impairs the cells' ability to gain energy through oxidative phosphorylation. Glucose limitation increases the expression of programed cell death protein-1 and reduces functions of activated CD8(+) T cells. A combination of hypoxia and hypoglycemia, as is common in solid tumors, places CD8(+) TILs at dual metabolic jeopardy by affecting both major pathways of energy production. Recently, a number of studies addressed the effects of metabolic stress on modulating CD8(+) T cell metabolism, differentiation, and functions. Here, we discuss recent findings on how different types of metabolic stress within the TME shape the tumor-killing capacity of CD8(+) T cells. We propose that manipulating the metabolism of TILs to more efficiently utilize nutrients, especially during intermittent periods of hypoxia could maximize their performance, prolong their survival and improve the efficacy of active cancer immunotherapy. PMID- 26904022 TI - Balancing Immune Protection and Immune Pathology by CD8(+) T-Cell Responses to Influenza Infection. AB - Influenza A virus (IAV) is a significant human pathogen causing annual epidemics and periodic pandemics. CD8(+) cytotoxic T lymphocyte (CTL)-mediated immunity contributes to the clearance of virus-infected cells, and CTL immunity targeting the conserved internal proteins of IAVs is a key protection mechanism when neutralizing antibodies are absent during heterosubtypic IAV infection. However, CTL infiltration into the airways, its cytotoxicity, and the effects of produced proinflammatory cytokines can cause severe lung tissue injury, thereby contributing to immunopathology. Studies have discovered complicated and exquisite stimulatory and inhibitory mechanisms that regulate CTL magnitude and effector activities during IAV infection. Here, we review the state of knowledge on the roles of IAV-specific CTLs in immune protection and immunopathology during IAV infection in animal models, highlighting the key findings of various requirements and constraints regulating the balance of immune protection and pathology involved in CTL immunity. We also discuss the evidence of cross reactive CTL immunity as a positive correlate of cross-subtype protection during secondary IAV infection in both animal and human studies. We argue that the effects of CTL immunity on protection and immunopathology depend on multiple layers of host and viral factors, including complex host mechanisms to regulate CTL magnitude and effector activity, the pathogenic nature of the IAV, the innate response milieu, and the host historical immune context of influenza infection. Future efforts are needed to further understand these key host and viral factors, especially to differentiate those that constrain optimally effective CTL antiviral immunity from those necessary to restrain CTL-mediated non-specific immunopathology in the various contexts of IAV infection, in order to develop better vaccination and therapeutic strategies for modifying protective CTL immunity. PMID- 26904024 TI - Peracetic Acid Treatment Generates Potent Inactivated Oral Vaccines from a Broad Range of Culturable Bacterial Species. AB - Our mucosal surfaces are the main sites of non-vector-borne pathogen entry, as well as the main interface with our commensal microbiota. We are still only beginning to understand how mucosal adaptive immunity interacts with commensal and pathogenic microbes to influence factors such as infectivity, phenotypic diversity, and within-host evolution. This is in part due to difficulties in generating specific mucosal adaptive immune responses without disrupting the mucosal microbial ecosystem itself. Here, we present a very simple tool to generate inactivated mucosal vaccines from a broad range of culturable bacteria. Oral gavage of 10(10) peracetic acid-inactivated bacteria induces high-titer specific intestinal IgA in the absence of any measurable inflammation or species invasion. As a proof of principle, we demonstrate that this technique is sufficient to provide fully protective immunity in the murine model of invasive non-typhoidal Salmonellosis, even in the face of severe innate immune deficiency. PMID- 26904027 TI - Erratum: Novel Immune Check-Point Regulators in Tolerance Maintenance. AB - [This corrects the article on p. 421 in vol. 6, PMID: 26347744.]. PMID- 26904028 TI - Editorial: Interaction Between Hyaluronic Acid and Its Receptors (CD44, RHAMM) Regulates the Activity of Inflammation and Cancer. PMID- 26904025 TI - Clearance Deficiency and Cell Death Pathways: A Model for the Pathogenesis of SLE. AB - Alterations of cell death pathways, including apoptosis and the neutrophil specific kind of death called NETosis, can represent a potential source of autoantigens. Defects in the clearance of apoptotic cells may be responsible for the initiation of systemic autoimmunity in several chronic inflammatory diseases, including systemic lupus erythematosus (SLE). Autoantigens are released mainly from secondary necrotic cells because of a defective clearance of apoptotic cells or an inefficient degradation of DNA-containing neutrophil extracellular traps (NETs). These modified autoantigens are presented by follicular dendritic cells to autoreactive B cells in germinal centers of secondary lymphoid organs. This results in the loss of self-tolerance and production of autoantibodies, a unifying feature of SLE. Immune complexes (IC) are formed from autoantibodies bound to uncleared cellular debris in blood or tissues. Clearance of IC by blood phagocytes, macrophages, and dendritic cells leads to proinflammatory cytokine secretion. In particular, plasmacytoid dendritic cells produce high amounts of interferon-alpha upon IC uptake, thereby contributing to the interferon signature of patients with SLE. The clearance of antinuclear IC via Fc-gamma receptors is considered a central event in amplifying inflammatory immune responses in SLE. Along with this, the accumulation of cell remnants represents an initiating event of the etiology, while the subsequent generation of autoantibodies against nuclear antigens (including NETs) results in the perpetuation of inflammation and tissue damage in patients with SLE. Here, we discuss the implications of defective clearance of apoptotic cells and NETs in the development of clinical manifestations in SLE. PMID- 26904026 TI - Ocular Immune Privilege and Transplantation. AB - Allografts are afforded a level of protection from rejection within immune privileged tissues. Immune-privileged tissues involve mechanisms that suppress inflammation and promote immune tolerance. There are anatomical features, soluble factors, membrane-associated proteins, and alternative antigen-presenting cells (APC) that contribute to allograft survival in the immune-privileged tissue. This review presents the current understanding of how the mechanism of ocular immune privilege promotes tolerogenic activity by APC, and T cells in response to the placement of foreign antigen within the ocular microenvironment. Discussed will be the unique anatomical, cellular, and molecular mechanisms that lessen the chance for graft destroying immune responses within the eye. As more is understood about the molecular mechanisms of ocular immune privilege greater is the potential for using these molecular mechanisms in therapies to prevent allograft rejection. PMID- 26904029 TI - Commentary: Basic Research in HIV Vaccinology Is Hampered by Reductionist Thinking. PMID- 26904031 TI - Transcriptomic Analysis for Different Sex Types of Ricinus communis L. during Development from Apical Buds to Inflorescences by Digital Gene Expression Profiling. AB - The castor plant (Ricinus communis L.) is a versatile industrial oilseed crop with a diversity of sex patterns, its hybrid breeding for improving yield and high purity is still hampered by genetic instability of female and poor knowledge of sex expression mechanisms. To obtain some hints involved in sex expression and provide the basis for further insight into the molecular mechanisms of castor plant sex determination, we performed DGE analysis to investigate differences between the transcriptomes of apices and racemes derived from female (JXBM0705P) and monoecious (JXBM0705M) lines. A total of 18 DGE libraries were constructed from the apices and racemes of a wild monoecious line and its isogenic female derivative at three stages of apex development, in triplicate. Approximately 5.7 million clean tags per library were generated and mapped to the reference castor genome. Transcriptomic analysis showed that identical dynamic changes of gene expression were indicated in monoecious and female apical bud during its development from vegetation to reproduction, with more genes expressed at the raceme formation and infant raceme stages compare to the early leaf bud stage. More than 3000 of differentially expressed genes (DEGs) were detected in Ricinus apices at three developmental stages between two different sex types. A number of DEGs involved in hormone response and biosynthesis, such as auxin response and transport, transcription factors, signal transduction, histone demethylation/methylation, programmed cell death, and pollination, putatively associated with sex expression and reproduction were discovered, and the selected DEGs showed consistent expression between qRT-PCR validation and the DGE patterns. Most of those DEGs were suppressed at the early leaf stage in buds of the mutant, but then activated at the following transition stage (5-7-leaf stage) of buds in the mutant, and ultimately, the number of up-regulated DEGs was equal to that of down-regulation in the small raceme of the mutant. In this study, a large number of DEGs and some suggestions involved in sex expression and reproduction were discovered using DGE analysis, which provides large information and valuable hints for next insights into the molecular mechanism of sex determination. It is useful for other further studies in Ricinus. PMID- 26904032 TI - Transcriptome Analysis of Dendrobium officinale and its Application to the Identification of Genes Associated with Polysaccharide Synthesis. AB - Dendrobium officinale is one of the most important Chinese medicinal herbs. Polysaccharides are one of the main active ingredients of D. officinale. To identify the genes that maybe related to polysaccharides synthesis, two cDNA libraries were prepared from juvenile and adult D. officinale, and were named Dendrobium-1 and Dendrobium-2, respectively. Illumina sequencing for Dendrobium-1 generated 102 million high quality reads that were assembled into 93,881 unigenes with an average sequence length of 790 base pairs. The sequencing for Dendrobium 2 generated 86 million reads that were assembled into 114,098 unigenes with an average sequence length of 695 base pairs. Two transcriptome databases were integrated and assembled into a total of 145,791 unigenes. Among them, 17,281 unigenes were assigned to 126 KEGG pathways while 135 unigenes were involved in fructose and mannose metabolism. Gene Ontology analysis revealed that the majority of genes were associated with metabolic and cellular processes. Furthermore, 430 glycosyltransferase and 89 cellulose synthase genes were identified. Comparative analysis of both transcriptome databases revealed a total of 32,794 differential expression genes (DEGs), including 22,051 up-regulated and 10,743 down-regulated genes in Dendrobium-2 compared to Dendrobium-1. Furthermore, a total of 1142 and 7918 unigenes showed unique expression in Dendrobium-1 and Dendrobium-2, respectively. These DEGs were mainly correlated with metabolic pathways and the biosynthesis of secondary metabolites. In addition, 170 DEGs belonged to glycosyltransferase genes, 37 DEGs were related to cellulose synthase genes and 627 DEGs encoded transcription factors. This study substantially expands the transcriptome information for D. officinale and provides valuable clues for identifying candidate genes involved in polysaccharide biosynthesis and elucidating the mechanism of polysaccharide biosynthesis. PMID- 26904034 TI - Editorial: Plant Single Cell Type Systems Biology. PMID- 26904033 TI - Genome-Wide Identification and Expression Analysis of the WRKY Gene Family in Cassava. AB - The WRKY family, a large family of transcription factors (TFs) found in higher plants, plays central roles in many aspects of physiological processes and adaption to environment. However, little information is available regarding the WRKY family in cassava (Manihot esculenta). In the present study, 85 WRKY genes were identified from the cassava genome and classified into three groups according to conserved WRKY domains and zinc-finger structure. Conserved motif analysis showed that all of the identified MeWRKYs had the conserved WRKY domain. Gene structure analysis suggested that the number of introns in MeWRKY genes varied from 1 to 5, with the majority of MeWRKY genes containing three exons. Expression profiles of MeWRKY genes in different tissues and in response to drought stress were analyzed using the RNA-seq technique. The results showed that 72 MeWRKY genes had differential expression in their transcript abundance and 78 MeWRKY genes were differentially expressed in response to drought stresses in different accessions, indicating their contribution to plant developmental processes and drought stress resistance in cassava. Finally, the expression of 9 WRKY genes was analyzed by qRT-PCR under osmotic, salt, ABA, H2O2, and cold treatments, indicating that MeWRKYs may be involved in different signaling pathways. Taken together, this systematic analysis identifies some tissue specific and abiotic stress-responsive candidate MeWRKY genes for further functional assays in planta, and provides a solid foundation for understanding of abiotic stress responses and signal transduction mediated by WRKYs in cassava. PMID- 26904035 TI - Analysis of Sensitive CO2 Pathways and Genes Related to Carbon Uptake and Accumulation in Chlamydomonas reinhardtii through Genomic Scale Modeling and Experimental Validation. AB - The development of microalgae sustainable applications needs better understanding of microalgae biology. Moreover, how cells coordinate their metabolism toward biomass accumulation is not fully understood. In this present study, flux balance analysis (FBA) was performed to identify sensitive metabolic pathways of Chlamydomonas reinhardtii under varied CO2 inputs. The metabolic network model of Chlamydomonas was updated based on the genome annotation data and sensitivity analysis revealed CO2 sensitive reactions. Biological experiments were performed with cells cultivated at 0.04% (air), 2.5, 5, 8, and 10% CO2 concentration under controlled conditions and cell growth profiles and biomass content were measured. Pigments, lipids, proteins, and starch were further quantified for the reference low (0.04%) and high (10%) CO2 conditions. The expression level of candidate genes of sensitive reactions was measured and validated by quantitative real time PCR. The sensitive analysis revealed mitochondrial compartment as the major affected by changes on the CO2 concentrations and glycolysis/gluconeogenesis, glyoxylate, and dicarboxylate metabolism among the affected metabolic pathways. Genes coding for glycerate kinase (GLYK), glycine cleavage system, H-protein (GCSH), NAD-dependent malate dehydrogenase (MDH3), low-CO2 inducible protein A (LCIA), carbonic anhydrase 5 (CAH5), E1 component, alpha subunit (PDC3), dual function alcohol dehydrogenase/acetaldehyde dehydrogenase (ADH1), and phosphoglucomutase (GPM2), were defined, among other genes, as sensitive nodes in the metabolic network simulations. These genes were experimentally responsive to the changes in the carbon fluxes in the system. We performed metabolomics analysis using mass spectrometry validating the modulation of carbon dioxide responsive pathways and metabolites. The changes on CO2 levels mostly affected the metabolism of amino acids found in the photorespiration pathway. Our updated metabolic network was compared to previous model and it showed more consistent results once considering the experimental data. Possible roles of the sensitive pathways in the biomass metabolism are discussed. PMID- 26904036 TI - Plants as Biofactories: Postharvest Stress-Induced Accumulation of Phenolic Compounds and Glucosinolates in Broccoli Subjected to Wounding Stress and Exogenous Phytohormones. AB - Broccoli contains high levels of bioactive molecules and is considered a functional food. In this study, postharvest treatments to enhance the concentration of glucosinolates and phenolic compounds were evaluated. Broccoli whole heads were wounded to obtain florets and wounded florets (florets cut into four even pieces) and stored for 24 h at 20 degrees C with or without exogenous ethylene (ET, 1000 ppm) or methyl jasmonate (MeJA, 250 ppm). Whole heads were used as a control for wounding treatments. Regarding glucosinolate accumulation, ET selectively induced the 4-hydroxylation of glucobrassicin in whole heads, resulting in ~223% higher 4-hydroxyglucobrassicin than time 0 h samples. Additionally, glucoraphanin was increased by ~53% in whole heads treated with ET, while neoglucobrassicin was greatly accumulated in wounded florets treated with ET or MeJA, showing increases of ~193 and ~286%, respectively. On the other hand, although only whole heads stored without phytohormones showed higher concentrations of phenolic compounds, which was reflected in ~33, ~30, and ~46% higher levels of 1,2,2-trisinapoylgentiobose, 1,2-diferulolylgentiobiose, and 1,2 disinapoyl-2-ferulolylgentiobiose, respectively; broccoli florets stored under air control conditions showed enhanced concentrations of 3-O-caffeoylquinic acid, 1,2-disinapoylgentiobiose, and 1,2-disinapoyl-2-ferulolylgentiobiose (~22, ~185, and ~65% more, respectively). Furthermore, exogenous ET and MeJA impeded individual phenolics accumulation. Results allowed the elucidation of simple and effective postharvest treatment to enhance the content of individual glucosinolates and phenolic compounds in broccoli. The stressed-broccoli tissue could be subjected to downstream processing in order to extract and purify bioactive molecules with applications in the dietary supplements, agrochemical and cosmetics markets. PMID- 26904030 TI - Heavy Metal Tolerance in Plants: Role of Transcriptomics, Proteomics, Metabolomics, and Ionomics. AB - Heavy metal contamination of soil and water causing toxicity/stress has become one important constraint to crop productivity and quality. This situation has further worsened by the increasing population growth and inherent food demand. It has been reported in several studies that counterbalancing toxicity due to heavy metal requires complex mechanisms at molecular, biochemical, physiological, cellular, tissue, and whole plant level, which might manifest in terms of improved crop productivity. Recent advances in various disciplines of biological sciences such as metabolomics, transcriptomics, proteomics, etc., have assisted in the characterization of metabolites, transcription factors, and stress inducible proteins involved in heavy metal tolerance, which in turn can be utilized for generating heavy metal-tolerant crops. This review summarizes various tolerance strategies of plants under heavy metal toxicity covering the role of metabolites (metabolomics), trace elements (ionomics), transcription factors (transcriptomics), various stress-inducible proteins (proteomics) as well as the role of plant hormones. We also provide a glance of some strategies adopted by metal-accumulating plants, also known as "metallophytes." PMID- 26904038 TI - Maize Plant Resilience to N Stress and Post-silking N Capacity Changes over Time: A Review. AB - We conducted a synthesis analysis on data from 86 published field experiments conducted from 1903 to 2014 to explore the specific consequences of post-silking N accumulation (PostN) in New Era vs. Old Era hybrids on grain yield (GY) and recovery from plant N stress at flowering (R1 stage). The Old Era encompassed studies using genotypes released before, and including, 1990 and the New Era included all studies using genotypes released from 1991 to 2014. Mean N fertilizer rates for experiments in the Old and New Era were similar (170 and 172 kg ha(-1), respectively), but plant densities averaged 5.0 plants m(-2) in the Old Era vs. 7.3 plants m(-2) in the New Era studies. Whole-plant N stress at R1 for each hybrid, environment and management combination was ranked into one of three categories relative to the N Nutrition Index (NNI). The key findings from this analysis are: (i) New Era genotypes increased the proportion of the total plant N at maturity accumulated post-silking (%PostN) as N stress levels at R1 increased-demonstrating improved adaptability to low N environments, (ii) New Era hybrids maintained similar GY on a per plant basis under both low and high N stress at R1 despite being subject to much higher population stress, (iii) PostN is more strongly correlated to GY (both eras combined) when under severe R1 N stress than under less acute N stress at R1, (iv) the New Era accumulated more total N (an increase of 30 kg N ha(-1)) and higher %PostN (an increase from 30% in Old to 36% in New Era), and (v) the change in stover dry weight from silking to physiological maturity (DeltaStover) has a positive, linear relationship with PostN in the Old Era but less so in the New Era. This increased understanding of how modern genotypes accumulate more N in the reproductive stage and have more PostN and GY resilience to mid-season N stress, even when grown at much higher plant densities, will assist trait selection and N management research directed to improving maize yields and N efficiencies simultaneously. PMID- 26904037 TI - Coordinated Changes in Antioxidative Enzymes Protect the Photosynthetic Machinery from Salinity Induced Oxidative Damage and Confer Salt Tolerance in an Extreme Halophyte Salvadora persica L. AB - Salinity-induced modulations in growth, photosynthetic pigments, relative water content (RWC), lipid peroxidation, photosynthesis, photosystem II efficiency, and changes in activity of various antioxidative enzymes were studied in the halophyte Salvadora persica treated with various levels of salinity (0, 250, 500, 750, and 1000 mM NaCl) to obtain an insight into the salt tolerance ability of this halophyte. Both fresh and dry biomass as well as leaf area (LA) declined at all levels of salinity whereas salinity caused an increase in leaf succulence. A gradual increase was observed in the Na(+) content of leaf with increasing salt concentration up to 750 mM NaCl, but at higher salt concentration (1000 mM NaCl), the Na(+) content surprisingly dropped down to the level of 250 mM NaCl. The chlorophyll and carotenoid contents of the leaf remained unaffected by salinity. The photosynthetic rate (PN), stomatal conductance (gs), the transpiration rate (E), quantum yield of PSII (PhiPSII), photochemical quenching (qP), and electron transport rate remained unchanged at low salinity (250 to 500 mM NaCl) whereas, significant reduction in these parameters were observed at high salinity (750 to 1000 mM NaCl). The RWC% and water use efficiency (WUE) of leaf remained unaffected by salinity. The salinity had no effect on maximum quantum efficiency of PS II (Fv/Fm) which indicates that PS II is not perturbed by salinity-induced oxidative damage. Analysis of the isoforms of antioxidative enzymes revealed that the leaves of S. persica have two isoforms each of Mn-SOD and Fe-SOD and one isoform of Cu-Zn SOD, three isoforms of POX, two isoforms of APX and one isoform of CAT. There was differential responses in activity and expression of different isoforms of various antioxidative enzymes. The malondialdehyde (MDA) content (a product of lipid peroxidation) of leaf remained unchanged in S. persica treated with various levels of salinity. Our results suggest that the absence of pigment degradation, the reduction of water loss, and the maintenance of WUE and protection of PSII from salinity-induced oxidative damage by the coordinated changes in antioxidative enzymes are important factors responsible for salt tolerance of S. persica. PMID- 26904040 TI - Arabidopsis: An Adequate Model for Dicot Root Systems? AB - The Arabidopsis root system is frequently considered to have only three classes of root: primary, lateral, and adventitious. Research with other plant species has suggested up to eight different developmental/functional classes of root for a given plant root system. If Arabidopsis has only three classes of root, it may not be an adequate model for eudicot plant root systems. Recent research, however, can be interpreted to suggest that pre-flowering Arabidopsis does have at least five (5) of these classes of root. This then suggests that Arabidopsis root research can be considered an adequate model for dicot plant root systems. PMID- 26904039 TI - Antigen Production in Plant to Tackle Infectious Diseases Flare Up: The Case of SARS. AB - Severe acute respiratory syndrome (SARS) is a dangerous infection with pandemic potential. It emerged in 2002 and its aetiological agent, the SARS Coronavirus (SARS-CoV), crossed the species barrier to infect humans, showing high morbidity and mortality rates. No vaccines are currently licensed for SARS-CoV and important efforts have been performed during the first outbreak to develop diagnostic tools. Here we demonstrate the transient expression in Nicotiana benthamiana of two important antigenic determinants of the SARS-CoV, the nucleocapsid protein (N) and the membrane protein (M) using a virus-derived vector or agro-infiltration, respectively. For the M protein, this is the first description of production in plants, while for plant-derived N protein we demonstrate that it is recognized by sera of patients from the SARS outbreak in Hong Kong in 2003. The availability of recombinant N and M proteins from plants opens the way to further evaluation of their potential utility for the development of diagnostic and protection/therapy tools to be quickly manufactured, at low cost and with minimal risk, to face potential new highly infectious SARS-CoV outbreaks. PMID- 26904041 TI - Elicitin-Induced Distal Systemic Resistance in Plants is Mediated Through the Protein-Protein Interactions Influenced by Selected Lysine Residues. AB - Elicitins are a family of small proteins with sterol-binding activity that are secreted by Phytophthora and Pythium sp. classified as oomycete PAMPs. Although alpha- and beta-elicitins bind with the same affinity to one high affinity binding site on the plasma membrane, beta-elicitins (possessing 6-7 lysine residues) are generally 50- to 100-fold more active at inducing distal HR and systemic resistance than the alpha-isoforms (with only 1-3 lysine residues). To examine the role of lysine residues in elicitin biological activity, we employed site-directed mutagenesis to prepare a series of beta-elicitin cryptogein variants with mutations on specific lysine residues. In contrast to direct infiltration of protein into leaves, application to the stem revealed a rough correlation between protein's charge and biological activity, resulting in protection against Phytophthora parasitica. A detailed analysis of proteins' movement in plants showed no substantial differences in distribution through phloem indicating differences in consequent apoplastic or symplastic transport. In this process, an important role of homodimer formation together with the ability to form a heterodimer with potential partner represented by endogenous plants LTPs is suggested. Our work demonstrates a key role of selected lysine residues in these interactions and stresses the importance of processes preceding elicitin recognition responsible for induction of distal systemic resistance. PMID- 26904042 TI - Sample Preparation for Mass Spectrometry Imaging of Plant Tissues: A Review. AB - Mass spectrometry imaging (MSI) is a mass spectrometry based molecular ion imaging technique. It provides the means for ascertaining the spatial distribution of a large variety of analytes directly on tissue sample surfaces without any labeling or staining agents. These advantages make it an attractive molecular histology tool in medical, pharmaceutical, and biological research. Likewise, MSI has started gaining popularity in plant sciences; yet, information regarding sample preparation methods for plant tissues is still limited. Sample preparation is a crucial step that is directly associated with the quality and authenticity of the imaging results, it therefore demands in-depth studies based on the characteristics of plant samples. In this review, a sample preparation pipeline is discussed in detail and illustrated through selected practical examples. In particular, special concerns regarding sample preparation for plant imaging are critically evaluated. Finally, the applications of MSI techniques in plants are reviewed according to different classes of plant metabolites. PMID- 26904043 TI - Soil Functional Zone Management: A Vehicle for Enhancing Production and Soil Ecosystem Services in Row-Crop Agroecosystems. AB - There is increasing global demand for food, bioenergy feedstocks and a wide variety of bio-based products. In response, agriculture has advanced production, but is increasingly depleting soil regulating and supporting ecosystem services. New production systems have emerged, such as no-tillage, that can enhance soil services but may limit yields. Moving forward, agricultural systems must reduce trade-offs between production and soil services. Soil functional zone management (SFZM) is a novel strategy for developing sustainable production systems that attempts to integrate the benefits of conventional, intensive agriculture, and no tillage. SFZM creates distinct functional zones within crop row and inter-row spaces. By incorporating decimeter-scale spatial and temporal heterogeneity, SFZM attempts to foster greater soil biodiversity and integrate complementary soil processes at the sub-field level. Such integration maximizes soil services by creating zones of 'active turnover', optimized for crop growth and yield (provisioning services); and adjacent zones of 'soil building', that promote soil structure development, carbon storage, and moisture regulation (regulating and supporting services). These zones allow SFZM to secure existing agricultural productivity while avoiding or minimizing trade-offs with soil ecosystem services. Moreover, the specific properties of SFZM may enable sustainable increases in provisioning services via temporal intensification (expanding the portion of the year during which harvestable crops are grown). We present a conceptual model of 'virtuous cycles', illustrating how increases in crop yields within SFZM systems could create self-reinforcing feedback processes with desirable effects, including mitigation of trade-offs between yield maximization and soil ecosystem services. Through the creation of functionally distinct but interacting zones, SFZM may provide a vehicle for optimizing the delivery of multiple goods and services in agricultural systems, allowing sustainable temporal intensification while protecting and enhancing soil functioning. PMID- 26904045 TI - Alternative Oxidase Pathway Optimizes Photosynthesis During Osmotic and Temperature Stress by Regulating Cellular ROS, Malate Valve and Antioxidative Systems. AB - The present study reveals the importance of alternative oxidase (AOX) pathway in optimizing photosynthesis under osmotic and temperature stress conditions in the mesophyll protoplasts of Pisum sativum. The responses of photosynthesis and respiration were monitored at saturating light intensity of 1000 MUmoles m(-2) s( 1) at 25 degrees C under a range of sorbitol concentrations from 0.4 to 1.0 M to induce hyper-osmotic stress and by varying the temperature of the thermo-jacketed pre-incubation chamber from 25 to 10 degrees C to impose sub-optimal temperature stress. Compared to controls (0.4 M sorbitol and 25 degrees C), the mesophyll protoplasts showed remarkable decrease in NaHCO3-dependent O2 evolution (indicator of photosynthetic carbon assimilation), under both hyper-osmotic (1.0 M sorbitol) and sub-optimal temperature stress conditions (10 degrees C), while the decrease in rates of respiratory O2 uptake were marginal. The capacity of AOX pathway increased significantly in parallel to increase in intracellular pyruvate and reactive oxygen species (ROS) levels under both hyper-osmotic stress and sub optimal temperature stress under the background of saturating light. The ratio of redox couple (Malate/OAA) related to malate valve increased in contrast to the ratio of redox couple (GSH/GSSG) related to antioxidative system during hyper osmotic stress. Further, the ratio of GSH/GSSG decreased in the presence of sub optimal temperature, while the ratio of Malate/OAA showed no visible changes. Also, the redox ratios of pyridine nucleotides increased under hyper-osmotic (NADH/NAD) and sub-optimal temperature (NADPH/NADP) stresses, respectively. However, upon restriction of AOX pathway by using salicylhydroxamic acid (SHAM), the observed changes in NaHCO3-dependent O2 evolution, cellular ROS, redox ratios of Malate/OAA, NAD(P)H/NAD(P) and GSH/GSSG were further aggravated under stress conditions with concomitant modulations in NADP-MDH and antioxidant enzymes. Taken together, the results indicated the importance of AOX pathway in optimizing photosynthesis under both hyper-osmotic stress and sub-optimal temperatures. Regulation of ROS through redox couples related to malate valve and antioxidant system by AOX pathway to optimize photosynthesis under these stresses are discussed. PMID- 26904046 TI - Grapevine Rootstocks Differentially Affect the Rate of Ripening and Modulate Auxin-Related Genes in Cabernet Sauvignon Berries. AB - In modern viticulture, grafting commercial grapevine varieties on interspecific rootstocks is a common practice required for conferring resistance to many biotic and abiotic stresses. Nevertheless, the use of rootstocks to gain these essential traits is also known to impact grape berry development and quality, although the underlying mechanisms are still poorly understood. In grape berries, the onset of ripening (veraison) is regulated by a complex network of mobile signals including hormones such as auxins, ethylene, abscisic acid, and brassinosteroids. Recently, a new rootstock, designated M4, was selected based on its enhanced tolerance to water stress and medium vigor. This study investigates the effect of M4 on Cabernet Sauvignon (CS) berry development in comparison to the commercial 1103P rootstock. Physical and biochemical parameters showed that the ripening rate of CS berries is faster when grafted onto M4. A multifactorial analysis performed on mRNA-Seq data obtained from skin and pulp of berries grown in both graft combinations revealed that genes controlling auxin action (ARF and Aux/IAA) represent one of main categories affected by the rootstock genotype. Considering that the level of auxin tightly regulates the transcription of these genes, we investigated the behavior of the main gene families involved in auxin biosynthesis and conjugation. Molecular and biochemical analyses confirmed a link between the rate of berry development and the modulation of auxin metabolism. Moreover, the data indicate that this phenomenon appears to be particularly pronounced in skin tissue in comparison to the flesh. PMID- 26904044 TI - Recent Advances in Utilizing Transcription Factors to Improve Plant Abiotic Stress Tolerance by Transgenic Technology. AB - Agricultural production and quality are adversely affected by various abiotic stresses worldwide and this will be exacerbated by the deterioration of global climate. To feed a growing world population, it is very urgent to breed stress tolerant crops with higher yields and improved qualities against multiple environmental stresses. Since conventional breeding approaches had marginal success due to the complexity of stress tolerance traits, the transgenic approach is now being popularly used to breed stress-tolerant crops. So identifying and characterizing the critical genes involved in plant stress responses is an essential prerequisite for engineering stress-tolerant crops. Far beyond the manipulation of single functional gene, engineering certain regulatory genes has emerged as an effective strategy now for controlling the expression of many stress-responsive genes. Transcription factors (TFs) are good candidates for genetic engineering to breed stress-tolerant crop because of their role as master regulators of many stress-responsive genes. Many TFs belonging to families AP2/EREBP, MYB, WRKY, NAC, bZIP have been found to be involved in various abiotic stresses and some TF genes have also been engineered to improve stress tolerance in model and crop plants. In this review, we take five large families of TFs as examples and review the recent progress of TFs involved in plant abiotic stress responses and their potential utilization to improve multiple stress tolerance of crops in the field conditions. PMID- 26904048 TI - Sensitive Indicators of Zonal Stipa Species to Changing Temperature and Precipitation in Inner Mongolia Grassland, China. AB - Climate change often induces shifts in plant functional traits. However, knowledge related to sensitivity of different functional traits and sensitive indicator representing plant growth under hydrothermal change remains unclear. Inner Mongolia grassland is predicted to be one of the terrestrial ecosystems which are most vulnerable to climate change. In this study, we analyzed the response of four zonal Stipa species (S. baicalensis, S. grandis, S. breviflora, and S. bungeana) from Inner Mongolia grassland to changing temperature (control, increased 1.5, 2, 4, and 6 degrees C), precipitation (decreased 30 and 15%, control, increased 15 and 30%) and their combined effects via climate control chambers. The relative change of functional traits in the unit of temperature and precipitation change was regarded as sensitivity coefficient and sensitive indicators were examined by pathway analysis. We found that sensitivity of the four Stipa species to changing temperature and precipitation could be ranked as follows: S. bungeana > S. grandis > S. breviflora > S. baicalensis. In particular, changes in leaf area, specific leaf area and root/shoot ratio could account for 86% of the changes in plant biomass in the four Stipa species. Also these three measurements were more sensitive to hydrothermal changes than the other functional traits. These three functional indicators reflected the combination of plant production capacity (leaf area), adaptive strategy (root/shoot ratio), instantaneous environmental effects (specific leaf area), and cumulative environmental effects (leaf area and root/shoot ratio). Thus, leaf area, specific leaf area and root/shoot ratio were chosen as sensitive indicators in response to changing temperature and precipitation for Stipa species. These results could provide the basis for predicting the influence of climate change on Inner Mongolia grassland based on the magnitude of changes in sensitive indicators. PMID- 26904047 TI - A Comparative Study of Ethylene Emanation upon Nitrogen Deficiency in Natural Accessions of Arabidopsis thaliana. AB - An original approach to develop sustainable agriculture with less nitrogen fertilizer inputs is to tackle the cross-talk between nitrogen nutrition and plant growth regulators. In particular the gaseous hormone, ethylene, is a prime target for that purpose. The variation of ethylene production in natural accessions of the model species Arabidopsis thaliana was explored in response to the nitrate supply. Ethylene was measured with a laser-based photoacoustic detector. First, experimental conditions were established with Columbia-0 (Col-0) accession, which was grown in vitro on horizontal plates across a range of five nitrate concentrations (0.5, 1, 2.5, 5, or 10 mM). The concentrations of 1 and 10 mM nitrate were retained for further characterization. Along with a decrease of total dry biomass and higher biomass allocation to the roots, the ethylene production was 50% more important at 1 mM than at 10 mM nitrate. The total transcript levels of 1-AMINOCYCLOPROPANE-1-CARBOXYLIC ACID SYNTHASES (ACS) in roots and those of ACC OXIDASES (ACO) in shoots increased by 100% between the same treatments. This was mainly due to higher transcript levels of ACS6 and of ACO2 and ACO4 respectively. The assumption was that during nitrogen deficiency, the greater biomass allocation in favor of the roots was controlled by ethylene being released in the shoots after conversion of ACC originating from the roots. Second, biomass and ethylene productions were measured in 20 additional accessions. Across all accessions, the total dry biomass and ethylene production were correlated negatively at 1 mM but positively at 10 mM nitrate. Furthermore, polymorphism was surveyed in ACC and ethylene biosynthesis genes and gene products among accessions. Very few substitutions modifying the amino acids properties in conserved motifs of the enzymes were found in the accessions. Natural variation of ethylene production could be further explored to improve Nitrogen Use Efficiency (NUE), in particular by manipulating features like the biomass production and the timing of senescence upon nitrogen limitation. PMID- 26904050 TI - Editorial: When Chemistry Meets Biology - Generating Innovative Concepts, Methods and Tools for Scientific Discovery in the Plant Sciences. PMID- 26904051 TI - Plant Clonal Integration Mediates the Horizontal Redistribution of Soil Resources, Benefiting Neighboring Plants. AB - Resources such as water taken up by plants can be released into soils through hydraulic redistribution and can also be translocated by clonal integration within a plant clonal network. We hypothesized that the resources from one (donor) microsite could be translocated within a clonal network, released into different (recipient) microsites and subsequently used by neighbor plants in the recipient microsite. To test these hypotheses, we conducted two experiments in which connected and disconnected ramet pairs of Potentilla anserina were grown under both homogeneous and heterogeneous water regimes, with seedlings of Artemisia ordosica as neighbors. The isotopes [(15)N] and deuterium were used to trace the translocation of nitrogen and water, respectively, within the clonal network. The water and nitrogen taken up by P. anserina ramets in the donor microsite were translocated into the connected ramets in the recipient microsites. Most notably, portions of the translocated water and nitrogen were released into the recipient microsite and were used by the neighboring A. ordosica, which increased growth of the neighboring A. ordosica significantly. Therefore, our hypotheses were supported, and plant clonal integration mediated the horizontal hydraulic redistribution of resources, thus benefiting neighboring plants. Such a plant clonal integration-mediated resource redistribution in horizontal space may have substantial effects on the interspecific relations and composition of the community and consequently on ecosystem processes. PMID- 26904049 TI - A Compact Model for the Complex Plant Circadian Clock. AB - The circadian clock is an endogenous timekeeper that allows organisms to anticipate and adapt to the daily variations of their environment. The plant clock is an intricate network of interlocked feedback loops, in which transcription factors regulate each other to generate oscillations with expression peaks at specific times of the day. Over the last decade, mathematical modeling approaches have been used to understand the inner workings of the clock in the model plant Arabidopsis thaliana. Those efforts have produced a number of models of ever increasing complexity. Here, we present an alternative model that combines a low number of equations and parameters, similar to the very earliest models, with the complex network structure found in more recent ones. This simple model describes the temporal evolution of the abundance of eight clock gene mRNA/protein and captures key features of the clock on a qualitative level, namely the entrained and free-running behaviors of the wild type clock, as well as the defects found in knockout mutants (such as altered free-running periods, lack of entrainment, or changes in the expression of other clock genes). Additionally, our model produces complex responses to various light cues, such as extreme photoperiods and non-24 h environmental cycles, and can describe the control of hypocotyl growth by the clock. Our model constitutes a useful tool to probe dynamical properties of the core clock as well as clock-dependent processes. PMID- 26904052 TI - MAPK Cascades in Guard Cell Signal Transduction. AB - Guard cells form stomata on the epidermis and continuously respond to endogenous and environmental stimuli to fine-tune the gas exchange and transpirational water loss, processes which involve mitogen-activated protein kinase (MAPK) cascades. MAPKs form three-tiered kinase cascades with MAPK kinases and MAPK kinase kinases, by which signals are transduced to the target proteins. MAPK cascade genes are highly conserved in all eukaryotes, and they play crucial roles in myriad developmental and physiological processes. MAPK cascades function during biotic and abiotic stress responses by linking extracellular signals received by receptors to cytosolic events and gene expression. In this review, we highlight recent findings and insights into MAPK-mediated guard cell signaling, including the specificity of MAPK cascades and the remaining questions. PMID- 26904053 TI - Salt Stress Affects the Redox Status of Arabidopsis Root Meristems. AB - We report the redox status (profiles) for specific populations of cells that comprise the Arabidopsis root tip. For recently germinated, 3-5-day-old seedlings we show that the region of the root tip with the most reduced redox status includes the root cap initials, the quiescent center and the most distal portion of the proximal meristem, and coincides with (overlays) the region of the auxin maximum. As one moves basally, further into the proximal meristem, and depending on the growth conditions, the redox status becomes more oxidized, with a 5-10 mV difference in redox potential between the two borders delimiting the proximal meristem. At the point on the root axis at which cells of the proximal meristem cease division and enter the transition zone, the redox potential levels off, and remains more or less unchanged throughout the transition zone. As cells leave the transition zone and enter the zone of elongation the redox potentials become more oxidized. Treating roots with salt (50, 100, and 150 mM NaCl) results in marked changes in root meristem structure and development, and is preceded by changes in the redox profile, which flattens, and initially becomes more oxidized, with pronounced changes in the redox potentials of the root cap, the root cap initials and the quiescent center. Roots exposed to relatively mild levels of salt (<100 mM) are able to re-establish a normal, pre-salt treatment redox profile 3-6 days after exposure to salt. Coincident with the salt-associated changes in redox profiles are changes in the distribution of auxin transporters (AUX1, PIN1/2), which become more diffuse in their localization. We conclude that salt stress affects root meristem maintenance, in part, through changes in redox and auxin transport. PMID- 26904054 TI - Combining Drought Survival via Summer Dormancy and Annual Biomass Productivity in Dactylis glomerata L. AB - Under Mediterranean climates, the best strategy to produce rain-fed fodder crops is to develop perennial drought resistant varieties. Summer dormancy present in native germplasm has been shown to confer a high level of survival under severe drought. Nevertheless it has also been shown to be negatively correlated with annual biomass productivity. The aim of this study was to analyze the correlations between summer dormancy and annual biomass productivity related traits and to identify quantitative trait loci (QTL) for these traits in a progeny of a summer dormant cocksfoot parent (Kasbah) and a summer active parent (Medly). A total of 283 offspring and the parents were phenotyped for summer dormancy, plant growth rate (PGR) and heading date in Morocco and for maximum leaf elongation rate (LERm) in France. The individuals were genotyped with a total of 325 markers including 59 AFLP, 64 SSR, and 202 DArT markers. The offspring exhibited a large quantitative variation for all measured traits. Summer dormancy showed a negative correlation with both PGR (-0.34 p < 0.005) and LERm (-0.27 p < 0.005). However, genotypes with both a high level of summer dormancy and a high level of PGR were detected in the progeny. One genetic map per parent was built with a total length of 377 and 423 cM for Kasbah and Medly, respectively. Both different and co-localized QTL for summer dormancy and PGR were identified. These results demonstrate that it should be possible to create summer dormant cocksfoot varieties with a high annual biomass productivity. PMID- 26904055 TI - Aromatic Glucosinolate Biosynthesis Pathway in Barbarea vulgaris and its Response to Plutella xylostella Infestation. AB - The inducibility of the glucosinolate resistance mechanism is an energy-saving strategy for plants, but whether induction would still be triggered by glucosinolate-tolerant Plutella xylostella (diamondback moth, DBM) after a plant had evolved a new resistance mechanism (e.g., saponins in Barbara vulgaris) was unknown. In B. vulgaris, aromatic glucosinolates derived from homo-phenylalanine are the dominant glucosinolates, but their biosynthesis pathway was unclear. In this study, we used G-type (pest-resistant) and P-type (pest-susceptible) B. vulgaris to compare glucosinolate levels and the expression profiles of their biosynthesis genes before and after infestation by DBM larvae. Two different stereoisomers of hydroxylated aromatic glucosinolates are dominant in G- and P type B. vulgaris, respectively, and are induced by DBM. The transcripts of genes in the glucosinolate biosynthesis pathway and their corresponding transcription factors were identified from an Illumina dataset of G- and P-type B. vulgaris. Many genes involved or potentially involved in glucosinolate biosynthesis were induced in both plant types. The expression patterns of six DBM induced genes were validated by quantitative PCR (qPCR), while six long-fragment genes were validated by molecular cloning. The core structure biosynthetic genes showed high sequence similarities between the two genotypes. In contrast, the sequence identity of two apparent side chain modification genes, the SHO gene in the G type and the RHO in P-type plants, showed only 77.50% identity in coding DNA sequences and 65.48% identity in deduced amino acid sequences. The homology to GS OH in Arabidopsis, DBM induction of the transcript and a series of qPCR and glucosinolate analyses of G-type, P-type and F1 plants indicated that these genes control the production of S and R isomers of 2-hydroxy-2-phenylethyl glucosinolate. These glucosinolates were significantly induced by P. xylostella larvae in both the susceptiple P-type and the resistant G-type, even though saponins are the main DBM-resistance causing metabolites in G-type plants. Indol 3-ylmethylglucosinolate was induced in the G-type only. These data will aid our understanding of the biosynthesis and induction of aromatic glucosinolates at the molecular level and also increase our knowledge of the complex mechanisms underpinning defense induction in plants. PMID- 26904057 TI - Vacuolar H(+)-Pyrophosphatase AVP1 is Involved in Amine Fungicide Tolerance in Arabidopsis thaliana and Provides Tridemorph Resistance in Yeast. AB - Amine fungicides are widely used as crop protectants. Their success is believed to be related to their ability to inhibit postlanosterol sterol biosynthesis in fungi, in particular sterol-Delta(8),Delta(7)-isomerases and sterol-Delta(14) reductases, with a concomitant accumulation of toxic abnormal sterols. However, their actual cellular effects and mechanisms of death induction are still poorly understood. Paradoxically, plants exhibit a natural resistance to amine fungicides although they have similar enzymes in postcicloartenol sterol biosynthesis that are also susceptible to fungicide inhibition. A major difference in vacuolar ion homeostasis between plants and fungi is the presence of a dual set of primary proton pumps in the former (V-ATPase and H(+) pyrophosphatase), but only the V-ATPase in the latter. Abnormal sterols affect the proton-pumping capacity of V-ATPases in fungi and this has been proposed as a major determinant in fungicide action. Using Saccharomyces cerevisiae as a model fungus, we provide evidence that amine fungicide treatment induced cell death by apoptosis. Cell death was concomitant with impaired H(+)-pumping capacity in vacuole vesicles and dependent on vacuolar proteases. Also, the heterologous expression of the Arabidopsis thaliana main H(+)-pyrophosphatase (AVP1) at the fungal vacuolar membrane reduced apoptosis levels in yeast and increased resistance to amine fungicides. Consistently, A. thaliana avp1 mutant seedlings showed increased susceptibility to this amine fungicide, particularly at the level of root development. This is in agreement with AVP1 being nearly the sole H(+)-pyrophosphatase gene expressed at the root elongation zones. All in all, the present data suggest that H(+)-pyrophosphatases are major determinants of plant tolerance to amine fungicides. PMID- 26904056 TI - Structural Coupling of Extrinsic Proteins with the Oxygen-Evolving Center in Photosystem II. AB - Photosystem II (PSII), which catalyzes photosynthetic water oxidation, is composed of more than 20 subunits, including membrane-intrinsic and -extrinsic proteins. The PSII extrinsic proteins shield the catalytic Mn4CaO5 cluster from the outside bulk solution and enhance binding of inorganic cofactors, such as Ca(2+) and Cl(-), in the oxygen-evolving center (OEC) of PSII. Among PSII extrinsic proteins, PsbO is commonly found in all oxygenic organisms, while PsbP and PsbQ are specific to higher plants and green algae, and PsbU, PsbV, CyanoQ, and CyanoP exist in cyanobacteria. In addition, red algae and diatoms have unique PSII extrinsic proteins, such as PsbQ' and Psb31, suggesting functional divergence during evolution. Recent studies with reconstitution experiments combined with Fourier transform infrared spectroscopy have revealed how the individual PSII extrinsic proteins affect the structure and function of the OEC in different organisms. In this review, we summarize our recent results and discuss changes that have occurred in the structural coupling of extrinsic proteins with the OEC during evolutionary history. PMID- 26904058 TI - Selection of Reference Genes for Normalization of MicroRNA Expression by RT-qPCR in Sugarcane Buds under Cold Stress. AB - Sugarcane, accounting for 80% of world's sugar, originates in the tropics but is cultivated mainly in the subtropics. Therefore, chilling injury frequently occurs and results in serious losses. Recent studies in various plant species have established microRNAs as key elements in the post-transcriptional regulation of response to biotic and abiotic stresses including cold stress. Though, its accuracy is largely influenced by the use of reference gene for normalization, quantitative PCR is undoubtedly a popular method used for identification of microRNAs. For identifying the most suitable reference genes for normalizing miRNAs expression in sugarcane under cold stress, 13 candidates among 17 were investigated using four algorithms: geNorm, NormFinder, deltaCt, and Bestkeeper, and four candidates were excluded because of unsatisfactory efficiency and specificity. Verification was carried out using cold-related genes miR319 and miR393 in cold-tolerant and sensitive cultivars. The results suggested that miR171/18S rRNA and miR171/miR5059 were the best reference gene sets for normalization for miRNA RT-qPCR, followed by the single miR171 and 18S rRNA. These results can aid research on miRNA responses during sugarcane stress, and the development of sugarcane tolerant to cold stress. This study is the first report concerning the reference gene selection of miRNA RT-qPCR in sugarcane. PMID- 26904060 TI - We Have an Inflation of Review Papers-for what Are Reviews Good? PMID- 26904059 TI - Detection of Diurnal Variation of Tomato Transcriptome through the Molecular Timetable Method in a Sunlight-Type Plant Factory. AB - The timing of measurement during plant growth is important because many genes are expressed periodically and orchestrate physiological events. Their periodicity is generated by environmental fluctuations as external factors and the circadian clock as the internal factor. The circadian clock orchestrates physiological events such as photosynthesis or flowering and it enables enhanced growth and herbivory resistance. These characteristics have possible applications for agriculture. In this study, we demonstrated the diurnal variation of the transcriptome in tomato (Solanum lycopersicum) leaves through molecular timetable method in a sunlight-type plant factory. Molecular timetable methods have been developed to detect periodic genes and estimate individual internal body time from these expression profiles in mammals. We sampled tomato leaves every 2 h for 2 days and acquired time-course transcriptome data by RNA-Seq. Many genes were expressed periodically and these expressions were stable across the 1st and 2nd days of measurement. We selected 143 time-indicating genes whose expression indicated periodically, and estimated internal time in the plant from these expression profiles. The estimated internal time was generally the same as the external environment time; however, there was a difference of more than 1 h between the two for some sampling points. Furthermore, the stress-responsive genes also showed weakly periodic expression, implying that they were usually expressed periodically, regulated by light-dark cycles as an external factor or the circadian clock as the internal factor, and could be particularly expressed when the plant experiences some specific stress under agricultural situations. This study suggests that circadian clock mediate the optimization for fluctuating environments in the field and it has possibilities to enhance resistibility to stress and floral induction by controlling circadian clock through light supplement and temperature control. PMID- 26904061 TI - Toward the Reconstitution of a Two-Enzyme Cascade for Resveratrol Synthesis on Potyvirus Particles. AB - The highly ordered protein backbone of virus particles makes them attractive candidates for use as enzyme nano-carriers (ENCs). We have previously developed a non-covalent and versatile approach for adhesion of enzymes to virus particles. This approach makes use of z33, a peptide derived from the B-domain of Staphylococcus aureus protein A, which binds to the Fc domain of many immunoglobulins. We have demonstrated that with specific antibodies addressed against the viral capsid proteins (CPs) an 87% coverage of z33-tagged proteins can be achieved on potyvirus particles. 4-coumarate coenzyme A ligase (4CL2) and stilbene synthase (STS) catalyze consecutive steps in the resveratrol synthetic pathway. In this study, these enzymes were modified to carry an N-terminal z33 peptide and a C-terminal 6xHis tag to obtain (z)4CL2(His) and (z)STS(His), respectively. A protein chimera, (z)4CL2::STS(His), with the same modifications was also generated from the genetic fusion of both mono-enzyme encoding genes. All z33 enzymes were biologically active after expression in Escherichia coli as revealed by LC-MS analysis to identify resveratrol and assembled readily into macromolecular complexes with Potato virus A particles and alpha-PVA CP antibodies. To test simultaneous immobilization-purification, we applied the double antibody sandwich - ELISA protocol to capture active z33-containg mono enzymes and protein chimera directly from clarified soluble cell lysates onto the virus particle surface. These immobilized enzymes were able to synthesize resveratrol. We present here a bottom up approach to immobilize active enzymes onto virus-based ENCs and discuss the potential to utilize this method in the purification and configuration of nano-devices. PMID- 26904062 TI - Improving Light Distribution by Zoom Lens for Electricity Savings in a Plant Factory with Light-Emitting Diodes. AB - The high energy consumption of a plant factory is the biggest issue in its rapid expansion, especially for lighting electricity, which has been solved to a large extent by light-emitting diodes (LED). However, the remarkable potential for further energy savings remains to be further investigated. In this study, an optical system applied just below the LED was designed. The effects of the system on the growth and photosynthesis of butterhead lettuce (Lactuca sativa var. capitata) were examined, and the performance of the optical improvement in energy savings was evaluated by comparison with the traditional LED illumination mode. The irradiation patterns used were LED with zoom lenses (Z-LED) and conventional non-lenses LED (C-LED). The seedlings in both treatments were exposed to the same light environment over the entire growth period. The improvement saved over half of the light source electricity, while prominently lowering the temperature. Influenced by this, the rate of photosynthesis sharply decreased, causing reductions in plant yield and nitrate content, while having no negative effects on morphological parameters and photosynthetic pigment contents. Nevertheless, the much higher light use efficiency of Z-LEDs makes this system a better approach to illumination in a plant factory with artificial lighting. PMID- 26904063 TI - Identification of WOX Family Genes in Selaginella kraussiana for Studies on Stem Cells and Regeneration in Lycophytes. AB - Plant stem cells give rise to all tissues and organs and also serve as the source for plant regeneration. The organization of plant stem cells has undergone a progressive change from simple to complex during the evolution of vascular plants. Most studies on plant stem cells have focused on model angiosperms, the most recently diverged branch of vascular plants. However, our knowledge of stem cell function in other vascular plants is limited. Lycophytes and euphyllophytes (ferns, gymnosperms, and angiosperms) are two existing branches of vascular plants that separated more than 400 million years ago. Lycophytes retain many of the features of early vascular plants. Based on genome and transcriptome data, we identified WUSCHEL-RELATED HOMEOBOX (WOX) genes in Selaginella kraussiana, a model lycophyte that is convenient for in vitro culture and observations of organ formation and regeneration. WOX genes are key players controlling stem cells in plants. Our results showed that the S. kraussiana genome encodes at least eight members of the WOX family, which represent an early stage of WOX family evolution. Identification of WOX genes in S. kraussiana could be a useful tool for molecular studies on the function of stem cells in lycophytes. PMID- 26904064 TI - Genetic Variation and Divergence of Genes Involved in Leaf Adaxial-Abaxial Polarity Establishment in Brassica rapa. AB - Alterations in leaf adaxial-abaxial (ad-ab) polarity are one of the main factors that influence leaf curvature. In Chinese cabbage, leaf incurvature is an essential prerequisite to the formation of a leafy head. Identifying ad-ab patterning genes and investigating their genetic variation may facilitate elucidation of the mechanisms underlying leaf incurvature during head formation. Comparative genomic analysis of 45 leaf ad-ab patterning genes in Brassica rapa based on 26 homologs of Arabidopsis thaliana indicated that these genes underwent expansion and were retained after whole genome triplication (WGT). We also assessed the nucleotide diversity and selection footprints of these 45 genes in a collection of 94 Brassica rapa accessions that were composed of heading and non heading morphotypes. Six of the 45 genes showed significant negative Tajima's D indices and nucleotide diversity reduction in heading accessions compared to those in non-heading accessions, indicating that they underwent purifying selection. Further testing of the BrARF3.1 gene, which was one of the selection signals from a larger collection, confirmed that purifying selection did occur. Our results provide genetic evidence that ad-ab patterning genes are involved in leaf incurvature, which is associated with formation of a leafy head, as well as promote an understanding of the genetic mechanism underlying leafy head formation in Chinese cabbage. PMID- 26904065 TI - Increased mtPDH Activity Through Antisense Inhibition of Mitochondrial Pyruvate Dehydrogenase Kinase Enhances Inflorescence Initiation, and Inflorescence Growth and Harvest Index at Elevated CO2 in Arabidopsis thaliana. AB - Mitochondrial pyruvate dehydrogenase (mtPDH) is a key respiratory enzyme that links glycolysis and the tricarboxylic acid cycle, and it is negatively regulated by mtPDH kinase (mtPDHK). Arabidopsis lines carrying either a constitutive or seed-specific antisense construct for mtPDHK were used to test the hypothesis that alteration of mtPDH activity in a tissue- and dosage-dependent manner will enhance reproductive growth particularly at elevated CO2 (EC) through a combined enhancement of source and sink activities. Constitutive transgenic lines showed increased mtPDH activity in rosette leaves at ambient CO2 (AC) and EC, and in immature seeds at EC. Seed-specific transgenic lines showed enhanced mtPDH activity in immature seeds. A strong relationship existed between seed mtPDH activity and inflorescence initiation at AC, and at EC inflorescence stem growth, silique number and seed harvest index were strongly related to seed mtPDH activity. Leaf photosynthetic rates showed an increase in rosette leaves of transgenic lines at AC and EC that correlated with enhanced inflorescence initiation. Collectively, the data show that mtPDHK plays a key role in regulating sink and source activities in Arabidopsis particularly during the reproductive phase. PMID- 26904066 TI - Overexpression of an Orchid (Dendrobium nobile) SOC1/TM3-Like Ortholog, DnAGL19, in Arabidopsis Regulates HOS1-FT Expression. AB - Flowering in the appropriate season is critical for successful reproduction in angiosperms. The orchid species, Dendrobium nobile, requires vernalization to achieve flowering in the spring, but the underlying regulatory network has not been identified to date. The MADS-box transcription factor DnAGL19 was previously identified in a study of low-temperature treated D. nobile buds and was suggested to regulate vernalization-induced flowering. In this study, phylogenetic analysis of DnAGL9 and the MADS-box containing proteins showed that DnAGL19 is phylogenetically closely related to the SOC1-like protein from orchid Dendrobium Chao Parya Smile, DOSOC1. The orchid clade closed to but is not included into the SOC1-1/TM3 clades associated with either eudicots or monocots, suggesting that DnAGL19 is an SOC1-1/TM3-like ortholog. DnAGL19 was found to be highly expressed in pseudobulbs, leaves, roots, and axillary buds but rarely in flowers, and to be substantially upregulated in axillary buds by prolonged low-temperature treatments. Overexpression of DnAGL19 in Arabidopsis thaliana resulted in a small but significantly reduced time to bolting, suggesting that flowering time was slightly accelerated under normal growth conditions. Consistent with this, the A. thaliana APETELA1 (AP1) gene was expressed at an earlier stage in transgenic lines than in wild type plants, while the FLOWERING LOCUS T (FT) gene was suppressed, suggesting that altered regulations on these transcription factors caused the weak promotion of flowering. HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENE 1 (HOS1) was slightly activated under the same conditions, suggesting that the HOS1-FT module may be involved in the DnAGL19-related network. Under vernalization conditions, FT expression was significantly upregulated, whereas HOS1 expression in the transgenic A. thaliana has a level similar to that in wild type. Taken together, these results suggest that DnAGL19 controls the action of the HOS1-FT module depending on temperature cues, which could contribute to regulation of D. nobile flowering time. These data provide insights into how flowering is fine-tuned in D. nobile to acclimate the plant to seasonal changes in temperature. PMID- 26904067 TI - Global Identification of the Full-Length Transcripts and Alternative Splicing Related to Phenolic Acid Biosynthetic Genes in Salvia miltiorrhiza. AB - Salvianolic acids are among the main bioactive components in Salvia miltiorrhiza, and their biosynthesis has attracted widespread interest. However, previous studies on the biosynthesis of phenolic acids using next-generation sequencing platforms are limited with regard to the assembly of full-length transcripts. Based on hybrid-seq (next-generation and single molecular real-time sequencing) of the S. miltiorrhiza root transcriptome, we experimentally identified 15 full length transcripts and four alternative splicing events of enzyme-coding genes involved in the biosynthesis of rosmarinic acid. Moreover, we herein demonstrate that lithospermic acid B accumulates in the phloem and xylem of roots, in agreement with the expression patterns of the identified key genes related to rosmarinic acid biosynthesis. According to co-expression patterns, we predicted that six candidate cytochrome P450s and five candidate laccases participate in the salvianolic acid pathway. Our results provide a valuable resource for further investigation into the synthetic biology of phenolic acids in S. miltiorrhiza. PMID- 26904068 TI - Functional Identification and Characterization of Genes Cloned from Halophyte Seashore Paspalum Conferring Salinity and Cadmium Tolerance. AB - Salinity-affected and heavy metal-contaminated soils limit the growth of glycophytic plants. Identifying genes responsible for superior tolerance to salinity and heavy metals in halophytes has great potential for use in developing salinity- and Cd-tolerant glycophytes. The objective of this study was to identify salinity- and Cd-tolerance related genes in seashore paspalum (Paspalum vaginatum), a halophytic perennial grass species, using yeast cDNA expression library screening method. Based on the Gateway-compatible vector system, a high quality entry library was constructed, which contained 9.9 * 10(6) clones with an average inserted fragment length of 1.48 kb representing a 100% full-length rate. The yeast expression libraries were screened in a salinity-sensitive and a Cd sensitive yeast mutant. The screening yielded 32 salinity-tolerant clones harboring 18 salinity-tolerance genes and 20 Cd-tolerant clones, including five Cd-tolerance genes. qPCR analysis confirmed that most of the 18 salinity tolerance and five Cd-tolerance genes were up-regulated at the transcript level in response to salinity or Cd stress in seashore paspalum. Functional analysis indicated that salinity-tolerance genes from seashore paspalum could be involved mainly in photosynthetic metabolism, antioxidant systems, protein modification, iron transport, vesicle traffic, and phospholipid biosynthesis. Cd-tolerance genes could be associated with regulating pathways that are involved in phytochelatin synthesis, HSFA4-related stress protection, CYP450 complex, and sugar metabolism. The 18 salinity-tolerance genes and five Cd-tolerance genes could be potentially used as candidate genes for genetic modification of glycophytic grass species to improve salinity and Cd tolerance and for further analysis of molecular mechanisms regulating salinity and Cd tolerance. PMID- 26904069 TI - Plant Phosphoglycerolipids: The Gatekeepers of Vascular Cell Differentiation. AB - In higher plants, the plant vascular system has evolved as an inter-organ communication network essential to deliver a wide range of signaling factors among distantly separated organs. To become conductive elements, phloem and xylem cells undergo a drastic differentiation program that involves the degradation of the majority of their organelles. While the molecular mechanisms regulating such complex process remain poorly understood, it is nowadays clear that phosphoglycerolipids display a pivotal role in the regulation of vascular tissue formation. In animal cells, this class of lipids is known to mediate acute responses as signal transducers and also act as constitutive signals that help defining organelle identity. Their rapid turnover, asymmetrical distribution across subcellular compartments as well as their ability to rearrange cytoskeleton fibers make phosphoglycerolipids excellent candidates to regulate complex morphogenetic processes such as vascular differentiation. Therefore, in this review we aim to summarize, emphasize and connect our current understanding about the involvement of phosphoglycerolipids in phloem and xylem differentiation. PMID- 26904070 TI - Identification of Mild Freezing Shock Response Pathways in Barley Based on Transcriptome Profiling. AB - Low temperature is a major abiotic stress affecting crop growth and productivity. A better understanding of low temperature tolerance mechanisms is imperative for developing the crop cultivars with improved tolerance. We herein performed an Illumina RNA-sequencing experiment using two barley genotypes differing in freezing tolerance (Nure, tolerant and Tremois, sensitive), to determine the transcriptome profiling and genotypic difference under mild freezing shock treatment after a very short acclimation for gene induction. A total of 6474 differentially expressed genes, almost evenly distributed on the seven chromosomes, were identified. The key DEGs could be classified into six signaling pathways, i.e., Ca(2+) signaling, PtdOH signaling, CBFs pathway, ABA pathway, jasmonate pathway, and amylohydrolysis pathway. Expression values of DEGs in multiple signaling pathways were analyzed and a hypothetical model of mild freezing shock tolerance mechanism was proposed. Expression and sequence profile of HvCBFs cluster within Frost resistance-H2, a major quantitative trait locus on 5H being closely related to low temperature tolerance in barley, were further illustrated, considering the crucial role of HvCBFs on freezing tolerance. It may be concluded that multiple signaling pathways are activated in concert when barley is exposed to mild freezing shock. The pathway network we presented may provide a platform for further exploring the functions of genes involved in low temperature tolerance in barley. PMID- 26904071 TI - The Diversity of the Pollen Tube Pathway in Plants: Toward an Increasing Control by the Sporophyte. AB - Plants, unlike animals, alternate multicellular diploid, and haploid generations in their life cycle. While this is widespread all along the plant kingdom, the size and autonomy of the diploid sporophyte and the haploid gametophyte generations vary along evolution. Vascular plants show an evolutionary trend toward a reduction of the gametophyte, reflected both in size and lifespan, together with an increasing dependence from the sporophyte. This has resulted in an overlooking of the importance of the gametophytic phase in the evolution of higher plants. This reliance on the sporophyte is most notorious along the pollen tube journey, where the male gametophytes have to travel a long way inside the sporophyte to reach the female gametophyte. Along evolution, there is a change in the scenery of the pollen tube pathway that favors pollen competition and selection. This trend, toward apparently making complicated what could be simple, appears to be related to an increasing control of the sporophyte over the gametophyte with implications for understanding plant evolution. PMID- 26904072 TI - The Coordination of Gene Expression within Photosynthesis Pathway for Acclimation of C4 Energy Crop Miscanthus lutarioriparius. AB - As a promising candidate for the second-generation C4 energy crop, Miscanthus lutarioriparius has well acclimated to the water-limited and high-light Loess Plateau in China by improving photosynthesis rate and water use efficiency (WUE) compared to its native habitat along Yangtze River. Photosynthetic genes were demonstrated as one major category of the candidate genes underlying the physiological superiority. To further study how photosynthetic genes interact to improve the acclimation potential of M. lutarioriparius, population expression patterns within photosynthesis pathway were explored between one mild environment and one harsh environment. We found that 108 transcripts in assembled transcriptome of M. lutarioriparius were highly similar to genes in three Kyoto Encyclopedia of Genes and Genomes (KEGG) photosynthesis pathways of sorghum and maize. Phylogenetic analyses using sorghum, maize, rice, and Arabidopsis genes of dark reaction identified 23 orthologs and 30 paralogs of M. lutarioriparius photosynthetic genes. These genes were also clustered into two kinds of expression pattern. 87% of transcripts in dark reaction were up-regulated and all 14 chloroplast-encoded transcripts in light reaction increased degradation in the harsh environment compared to the mild environment. Moreover, 80.8% of photosynthetic transcripts were coordinated at transcription level under the two environments. Interestingly, LHCI and PSI were significantly correlated with F ATPase and C4 cycle. Overall, this study indicates the coordinated expression between cyclic electron transport (consisting of LHCI, PSI, and ATPase) and CO2 concentrating mechanism (C4 cycle) could account for photosynthesis plasticity on M. lutarioriparius acclimation potential. PMID- 26904073 TI - Comparative Proteomic Analysis of Cultured Suspension Cells of the Halophyte Halogeton glomeratus by iTRAQ Provides Insights into Response Mechanisms to Salt Stress. AB - Soil salinity severely threatens land use capability and crop yields worldwide. An analysis of the molecular mechanisms of salt tolerance in halophytes will contribute to the development of salt-tolerant crops. In this study, a combination of physiological characteristics and iTRAQ-based proteomic approaches was conducted to investigate the molecular mechanisms underlying the salt response of suspension cell cultures of halophytic Halogeton glomeratus. These cells showed halophytic growth responses comparable to those of the whole plant. In total, 97 up-regulated proteins and 192 down-regulated proteins were identified as common to both 200 and 400 mM NaCl concentration treatments. Such salinity responsive proteins were mainly involved in energy, carbohydrate metabolism, stress defense, protein metabolism, signal transduction, cell growth, and cytoskeleton metabolism. Effective regulatory protein expression related to energy, stress defense, and carbohydrate metabolism play important roles in the salt-tolerance of H. glomeratus suspension cell cultures. However, known proteins regulating Na(+) efflux from the cytoplasm and its compartmentalization into the vacuole did not change significantly under salinity stress suggesting our existing knowledge concerning Na(+) extrusion and compartmentalization in halophytes needs to be evaluated further. Such data are discussed in the context of our current understandings of the mechanisms involved in the salinity response of the halophyte, H. glomeratus. PMID- 26904074 TI - Root-Lesion Nematodes Suppress Cabbage Aphid Population Development by Reducing Aphid Daily Reproduction. AB - Empirical studies have shown that belowground feeding herbivores can affect the performance of aboveground herbivores in different ways. Often the critical life history parameters underlying the observed performance effects remain unexplored. In order to better understand the cause for the observed effects on aboveground herbivores, these ecological mechanisms must be better understood. In this study we combined empirical experiments with a modeling approach to analyze the effect of two root feeding endoparasitic nematodes with different feeding strategies on the population growth of the aboveground feeding specialist aphid Brevicoryne brassicae on Brassica nigra. The aim was to test whether emerging differences in life history characteristics (days until reproduction, daily reproduction) would be sufficient to explain observed differences in aphid population development on plants with and without two species of nematodes. Aphid numbers were lower on plants with Pratylenchus penetrans in comparison to aphid numbers on plants with Meloidogyne spp. A dedicated experiment showed that aphid daily reproduction was lower on plants with P. penetrans (3.08 offspring female(-1) day(-1)) in comparison to both uninfested plants and plants with Meloidogyne spp. (3.50 offspring female(-1) day(-1)). The species-specific reduction of aphid reproduction appeared independent of changes in amino acids, soluble sugars or the glucosinolate sinigrin in the phloem. An individual-based model revealed that relatively small differences in reproduction rate per female were sufficient to yield a similar difference in aphid populations as was found in the empirical experiments. PMID- 26904075 TI - Development of a Two-Stage Microalgae Dewatering Process - A Life Cycle Assessment Approach. AB - Even though microalgal biomass is leading the third generation biofuel research, significant effort is required to establish an economically viable commercial scale microalgal biofuel production system. Whilst a significant amount of work has been reported on large-scale cultivation of microalgae using photo bioreactors and pond systems, research focus on establishing high performance downstream dewatering operations for large-scale processing under optimal economy is limited. The enormous amount of energy and associated cost required for dewatering large-volume microalgal cultures has been the primary hindrance to the development of the needed biomass quantity for industrial-scale microalgal biofuels production. The extremely dilute nature of large-volume microalgal suspension and the small size of microalgae cells in suspension create a significant processing cost during dewatering and this has raised major concerns towards the economic success of commercial-scale microalgal biofuel production as an alternative to conventional petroleum fuels. This article reports an effective framework to assess the performance of different dewatering technologies as the basis to establish an effective two-stage dewatering system. Bioflocculation coupled with tangential flow filtration (TFF) emerged a promising technique with total energy input of 0.041 kWh, 0.05 kg CO2 emissions and a cost of $ 0.0043 for producing 1 kg of microalgae biomass. A streamlined process for operational analysis of two-stage microalgae dewatering technique, encompassing energy input, carbon dioxide emission, and process cost, is presented. PMID- 26904076 TI - The Plant Heat Stress Transcription Factors (HSFs): Structure, Regulation, and Function in Response to Abiotic Stresses. AB - Abiotic stresses such as high temperature, salinity, and drought adversely affect the survival, growth, and reproduction of plants. Plants respond to such unfavorable changes through developmental, physiological, and biochemical ways, and these responses require expression of stress-responsive genes, which are regulated by a network of transcription factors (TFs), including heat stress transcription factors (HSFs). HSFs play a crucial role in plants response to several abiotic stresses by regulating the expression of stress-responsive genes, such as heat shock proteins (Hsps). In this review, we describe the conserved structure of plant HSFs, the identification of HSF gene families from various plant species, their expression profiling under abiotic stress conditions, regulation at different levels and function in abiotic stresses. Despite plant HSFs share highly conserved structure, their remarkable diversification across plants reflects their numerous functions as well as their integration into the complex stress signaling and response networks, which can be employed in crop improvement strategies via biotechnological intervention. PMID- 26904077 TI - The Arabidopsis Thylakoid Chloride Channel AtCLCe Functions in Chloride Homeostasis and Regulation of Photosynthetic Electron Transport. AB - Chloride ions can be translocated across cell membranes through Cl(-) channels or Cl(-)/H(+) exchangers. The thylakoid-located member of the Cl(-) channel CLC family in Arabidopsis thaliana (AtCLCe) was hypothesized to play a role in photosynthetic regulation based on the initial photosynthetic characterization of clce mutant lines. The reduced nitrate content of Arabidopsis clce mutants suggested a role in regulation of plant nitrate homeostasis. In this study, we aimed to further investigate the role of AtCLCe in the regulation of ion homeostasis and photosynthetic processes in the thylakoid membrane. We report that the size and composition of proton motive force were mildly altered in two independent Arabidopsis clce mutant lines. Most pronounced effects in the clce mutants were observed on the photosynthetic electron transport of dark-adapted plants, based on the altered shape and associated parameters of the polyphasic OJIP kinetics of chlorophyll a fluorescence induction. Other alterations were found in the kinetics of state transition and in the macro-organization of photosystem II supercomplexes, as indicated by circular dichroism measurements. Pre-treatment with KCl but not with KNO3 restored the wild-type photosynthetic phenotype. Analyses by transmission electron microscopy revealed a bow-like arrangement of the thylakoid network and a large thylakoid-free stromal region in chloroplast sections from the dark-adapted clce plants. Based on these data, we propose that AtCLCe functions in Cl(-) homeostasis after transition from light to dark, which affects chloroplast ultrastructure and regulation of photosynthetic electron transport. PMID- 26904078 TI - Physiological and Biochemical Mechanisms of Seed Priming-Induced Chilling Tolerance in Rice Cultivars. AB - Rice belongs to tropical and subtropical environments and is extremely sensitive to chilling stress particularly during emergence and early stages of seedling development. Seed priming can be a good approach to enhance rice germination and stand establishment under chilling stress. The present study examined the role of different seed priming techniques viz., hydropriming, osmopriming, redox priming, chemical priming, and hormonal priming, in enhancing the chilling tolerance in rice. The most effective reagents and their pre-optimized concentrations based on preliminary experiments were used in this study. Two different rice cultivars were sown under chilling stress (18 degrees C) and normal temperatures (28 degrees C) in separate growth chambers. A non-primed control treatment was also maintained for comparison. Chilling stress caused erratic and delayed germination, poor seedling growth, reduced starch metabolism, and lower respiration rate, while higher lipid peroxidation and hydrogen peroxide accumulation in rice seedlings of both cultivars. Nevertheless, all the seed priming treatments effectively alleviated the negative effects of chilling stress. In addition, seed priming treatments triggered the activities of superoxide dismutase, peroxidase, and catalase, and enhanced the accumulations of glutathione and free proline in rice seedlings, which suggests that these measures help prevent the rice seedlings from chilling induced oxidative stress. Chemical priming with selenium and hormonal priming with salicylic acid remained more effective treatments for both rice cultivars under chilling stress than all other priming treatments. The better performance and greater tolerance of primed rice seedlings was associated with enhanced starch metabolism, high respiration rate, lower lipid peroxidation, and strong antioxidative defense system under chilling stress. PMID- 26904079 TI - Diversity in Biosynthetic Pathways of Galactolipids in the Light of Endosymbiotic Origin of Chloroplasts. AB - Cyanobacteria and chloroplasts perform oxygenic photosynthesis, and share a common origin. Galactolipids are present in the photosynthetic membranes of both cyanobacteria and chloroplasts, but the biosynthetic pathways of the galactolipids are significantly different in the two systems. In this minireview, we explain the history of the discovery of the cyanobacterial pathway, and present a probable scenario of the evolution of the two pathways. PMID- 26904081 TI - Precision Automation of Cell Type Classification and Sub-Cellular Fluorescence Quantification from Laser Scanning Confocal Images. AB - While novel whole-plant phenotyping technologies have been successfully implemented into functional genomics and breeding programs, the potential of automated phenotyping with cellular resolution is largely unexploited. Laser scanning confocal microscopy has the potential to close this gap by providing spatially highly resolved images containing anatomic as well as chemical information on a subcellular basis. However, in the absence of automated methods, the assessment of the spatial patterns and abundance of fluorescent markers with subcellular resolution is still largely qualitative and time-consuming. Recent advances in image acquisition and analysis, coupled with improvements in microprocessor performance, have brought such automated methods within reach, so that information from thousands of cells per image for hundreds of images may be derived in an experimentally convenient time-frame. Here, we present a MATLAB based analytical pipeline to (1) segment radial plant organs into individual cells, (2) classify cells into cell type categories based upon Random Forest classification, (3) divide each cell into sub-regions, and (4) quantify fluorescence intensity to a subcellular degree of precision for a separate fluorescence channel. In this research advance, we demonstrate the precision of this analytical process for the relatively complex tissues of Arabidopsis hypocotyls at various stages of development. High speed and robustness make our approach suitable for phenotyping of large collections of stem-like material and other tissue types. PMID- 26904082 TI - 5-Aminolevulinic Acid Thins Pear Fruits by Inhibiting Pollen Tube Growth via Ca(2+)-ATPase-Mediated Ca(2+) Efflux. AB - Chemical fruit thinning has become a popular practice in modern fruit orchards for achieving high quality fruits, reducing costs of hand thinning and promoting return bloom. However, most of the suggested chemical thinners are often concerned for their detrimental effects and environmental problems. 5 Aminolevulic acid (ALA) is a natural, nontoxic, biodegradable, and environment friendly plant growth regulator. One of its outstanding roles is improving plant photosynthesis and fruit quality. Here, results showed that applying 100-200 mg/L ALA at full bloom stage significantly reduced pear fruit set. Both in vivo and in vitro studies showed that ALA significantly inhibited pollen germination and tube growth. ALA decreased not only cytosolic Ca(2+) concentration ([Ca(2+)]cyt) but also "tip-focused" [Ca(2+)]cyt gradient, indicating that ALA inhibited pollen tube growth by down-regulating calcium signaling. ALA drastically enhanced pollen Ca(2+)-ATPase activity, suggesting that ALA-induced decrease of calcium signaling probably resulted from activating calcium pump. The significant negative correlations between Ca(2+)-ATPase activity and pollen germination or pollen tube length further demonstrated the critical role of calcium pump in ALA's negative effect on pollen germination. Taken together, our results suggest that ALA at low concentrations is a potential biochemical thinner, and it inhibits pollen germination and tube growth via Ca(2+) efflux by activating Ca(2+)-ATPase, thereby thinning fruits by preventing fertilization. PMID- 26904080 TI - GIP Contributions to the Regulation of Centromere at the Interface Between the Nuclear Envelope and the Nucleoplasm. AB - Centromeres are known as specific chromatin domains without which eukaryotic cells cannot divide properly during mitosis. Despite the considerable efforts to understand the centromere/kinetochore assembly during mitosis, until recently, comparatively few studies have dealt with the regulation of centromere during interphase. Here, we briefly review and discuss past and recent advances about the architecture of centromeres and their regulation during the cell cycle. Furthermore, we highlight and discuss new findings and hypotheses regarding the specific regulation of centromeres in both plant and animal nuclei, especially with GIP proteins at the interface between the nuclear envelope and the nucleoplasm. PMID- 26904084 TI - Uneven HAK/KUP/KT Protein Diversity Among Angiosperms: Species Distribution and Perspectives. AB - HAK/KUP/KT K(+) transporters have been widely associated with K(+) transport across membranes in bacteria, fungi, and plants. Indeed some members of the plant HAK/KUP/KT family contribute to root K(+) uptake, notably at low external concentrations. Besides such role in acquisition, several studies carried out in Arabidopsis have shown that other members are also involved in developmental processes. With the publication of new plant genomes, a growing interest on plant species other than Arabidopsis has become evident. In order to understand HAK/KUP/KT diversity in these new plant genomes, we discuss the evolutionary trends of 913 HAK/KUP/KT sequences identified in 46 genomes revealing five major groups with an uneven distribution among angiosperms, notably between dicotyledonous and monocotyledonous species. This information evidenced the richness of crop genomes in HAK/KUP/KT transporters and supports their study for unraveling novel physiological roles of such transporters in plants. PMID- 26904086 TI - Disentangling Facilitation Along the Life Cycle: Impacts of Plant-Plant Interactions at Vegetative and Reproductive Stages in a Mediterranean Forb. AB - Facilitation enables plants to improve their fitness in stressful environments. The overall impact of plant-plant interactions on the population dynamics of protegees is the net result of both positive and negative effects that may act simultaneously along the plant life cycle, and depends on the environmental context. This study evaluates the impact of the nurse plant Juniperus sabina on different stages of the life cycle of the forb Helleborus foetidus. Growth, number of leaves, flowers, carpels, and seeds per flower were compared for 240 individuals collected under nurse canopies and in open areas at two sites with contrasting stress levels. Spatial associations with nurse plants and age structures were also checked. A structural equation model was built to test the effect of facilitation on fecundity, accounting for sequential steps from flowering to seed production. The net impact of nurse plants depended on a combination of positive and negative effects on vegetative and reproductive variables. Although nurse plants caused a decrease in flower production at the low-stress site, their net impact there was neutral. In contrast, at the high stress site the net outcome of plant-plant interactions was positive due to an increase in effective recruitment, plant density, number of viable carpels per flower, and fruit set under nurse canopies. The naturally lower rates of secondary growth and flower production at the high-stress site were compensated by the net positive impact of nurse plants here. Our results emphasize the need to evaluate entire processes and not only final outcomes when studying plant plant interactions. PMID- 26904083 TI - Computational Prediction of Effector Proteins in Fungi: Opportunities and Challenges. AB - Effector proteins are mostly secretory proteins that stimulate plant infection by manipulating the host response. Identifying fungal effector proteins and understanding their function is of great importance in efforts to curb losses to plant diseases. Recent advances in high-throughput sequencing technologies have facilitated the availability of several fungal genomes and 1000s of transcriptomes. As a result, the growing amount of genomic information has provided great opportunities to identify putative effector proteins in different fungal species. There is little consensus over the annotation and functionality of effector proteins, and mostly small secretory proteins are considered as effector proteins, a concept that tends to overestimate the number of proteins involved in a plant-pathogen interaction. With the characterization of Avr genes, criteria for computational prediction of effector proteins are becoming more efficient. There are 100s of tools available for the identification of conserved motifs, signature sequences and structural features in the proteins. Many pipelines and online servers, which combine several tools, are made available to perform genome-wide identification of effector proteins. In this review, available tools and pipelines, their strength and limitations for effective identification of fungal effector proteins are discussed. We also present an exhaustive list of classically secreted proteins along with their key conserved motifs found in 12 common plant pathogens (11 fungi and one oomycete) through an analytical pipeline. PMID- 26904085 TI - Characterization of Zinc and Cadmium Hyperaccumulation in Three Noccaea (Brassicaceae) Populations from Non-metalliferous Sites in the Eastern Pyrenees. AB - The Southern slope of the Pyrenees is the meridional limit for the distribution of several Noccaea populations. However, the systematic description of these populations and their hyperaccumulation mechanisms are not well established. Morphological and genetic analysis (ITS and 3 chloroplast regions) were used to identify Noccaea populations localized on non-metallicolous soils during a survey in the Catalonian Pyrenees. Cd and Zn concentrations were analyzed in soils and plants both sampled in the field and grown hydroponically. The expression of selected metal transporter genes was assessed by quantitative PCR. The populations were identified as Noccaea brachypetala (Jord.) F.K. Mey by conspicuous morphological traits. Principal component analysis provided a clear separation among N. brachypetala, Noccaea caerulescens J. Presl & C. Presl and Noccaea occitanica (Jord.) F.K. Mey., three Noccaea species reported in the Pyrenees. Contrastingly, ITS and cpDNA analyses were unable to clearly differentiate these taxa. Differences in the expression of the metal transporter genes HMA3, HMA4, and MTP1 between N. caerulescens and N. brachypetala, and those amongst the N. brachypetala populations suggest differences in the strategies for handling enhanced Cd and Zn availability. This is the first report demonstrating Cd and Zn hyperaccumulation by N. brachypetala both in the field and in hydroponics. This comprehensive study based on taxonomic, molecular, and physiological data allows both the correct identification of this species and the characterization of population differences in hyperaccumulation and tolerance of Zn and Cd. PMID- 26904087 TI - Autophagy, a Conserved Mechanism for Protein Degradation, Responds to Heat, and Other Abiotic Stresses in Capsicum annuum L. AB - Abiotic stresses negatively affect plants growth and development by inducing protein denaturation, and autophagy degrades the damaged proteins to alleviate their toxicity, however, little is known about the involvement of autophagy in pepper (Capsicum annuum L.) tolerances to abiotic stresses. In this study, we identified autophagy-related gene (ATG) members in the whole genome of pepper by HMM method and analyzed their expression profiles in response to heat and other abiotic stresses by quantitative real-time PCR. The results showed that the CaATG contained 15 core ATG members including 29 ATG proteins with their respective conserved functional domains, involving the whole process of autophagy. Under normal environmental condition, the expression of CaATG genes showed tissue- and developmental stage-specific patterns, while under abiotic stresses of salt, drought, heat, cold and carbohydrate starvation, the accumulation of autophagosome punctate increased and the expression level of CaATG genes changed with stress type-dependent pattern, which indicates the linkage of autophagy in pepper response to abiotic stresses. After treated with heat stress, both the number of up-regulated CaATG genes and the increment of autophagosome punctate were higher in pepper thermotolerant line R9 than those in thermosensitive line B6, implying an association of autophagy with heat tolerance. In addition, CaATG6 was predicted to interact with CaHSP90 family members. Our study suggests that autophagy is connected to pepper tolerances to heat and other abiotic stresses. PMID- 26904088 TI - Implementation of Genomic Prediction in Lolium perenne (L.) Breeding Populations. AB - Perennial ryegrass (Lolium perenne L.) is one of the most widely grown forage grasses in temperate agriculture. In order to maintain and increase its usage as forage in livestock agriculture, there is a continued need for improvement in biomass yield, quality, disease resistance, and seed yield. Genetic gain for traits such as biomass yield has been relatively modest. This has been attributed to its long breeding cycle, and the necessity to use population based breeding methods. Thanks to recent advances in genotyping techniques there is increasing interest in genomic selection from which genomically estimated breeding values are derived. In this paper we compare the classical RRBLUP model with state-of the-art machine learning techniques that should yield themselves easily to use in GS and demonstrate their application to predicting quantitative traits in a breeding population of L. perenne. Prediction accuracies varied from 0 to 0.59 depending on trait, prediction model and composition of the training population. The BLUP model produced the highest prediction accuracies for most traits and training populations. Forage quality traits had the highest accuracies compared to yield related traits. There appeared to be no clear pattern to the effect of the training population composition on the prediction accuracies. The heritability of the forage quality traits was generally higher than for the yield related traits, and could partly explain the difference in accuracy. Some population structure was evident in the breeding populations, and probably contributed to the varying effects of training population on the predictions. The average linkage disequilibrium between adjacent markers ranged from 0.121 to 0.215. Higher marker density and larger training population closely related with the test population are likely to improve the prediction accuracy. PMID- 26904089 TI - A Two-Component Regulatory System in Transcriptional Control of Photosystem Stoichiometry: Redox-Dependent and Sodium Ion-Dependent Phosphoryl Transfer from Cyanobacterial Histidine Kinase Hik2 to Response Regulators Rre1 and RppA. AB - Two-component systems (TCSs) are ubiquitous signaling units found in prokaryotes. A TCS consists of a sensor histidine kinase and a response regulator protein as signal transducers. These regulatory systems mediate acclimation to various environmental changes by coupling environmental cues to gene expression. Hik2 is a sensor histidine kinase and its gene is found in all cyanobacteria. Hik2 is the homolog of Chloroplast Sensor Kinase (CSK), a protein involved in redox regulation of chloroplast gene expression during changes in light quality in plants and algae. Here we describe biochemical characterization of the signaling mechanism of Hik2 and its phosphotransferase activity. Results presented here indicate that Hik2 undergoes autophosphorylation on a conserved histidine residue, and becomes rapidly dephosphorylated by the action of response regulators Rre1 and RppA. We also show that the autophosphorylation of Hik2 is specifically inhibited by sodium ions. PMID- 26904090 TI - Glutathione S-Transferase Gene Family in Gossypium raimondii and G. arboreum: Comparative Genomic Study and their Expression under Salt Stress. AB - Glutathione S-transferases (GSTs) play versatile functions in multiple aspects of plant growth and development. A comprehensive genome-wide survey of this gene family in the genomes of G. raimondii and G. arboreum was carried out in this study. Based on phylogenetic analyses, the GST gene family of both two diploid cotton species could be divided into eight classes, and approximately all the GST genes within the same subfamily shared similar gene structure. Additionally, the gene structures between the orthologs were highly conserved. The chromosomal localization analyses revealed that GST genes were unevenly distributed across the genome in both G. raimondii and G. arboreum. Tandem duplication could be the major driver for the expansion of GST gene families. Meanwhile, the expression analysis for the selected 40 GST genes showed that they exhibited tissue-specific expression patterns and their expression were induced or repressed by salt stress. Those findings shed lights on the function and evolution of the GST gene family in Gossypium species. PMID- 26904091 TI - Heterologous Expression of AtWRKY57 Confers Drought Tolerance in Oryza sativa. AB - Drought stress is a severe environmental factor that greatly restricts plant distribution and crop production. Recently, we have found that overexpressing AtWRKY57 enhanced drought tolerance in Arabidopsis thaliana. In this study, we further reported that the Arabidopsis WRKY57 transcription factor was able to confer drought tolerance to transgenic rice (Oryza sativa) plants. The enhanced drought tolerance of transgenic rice was resulted from the lower water loss rates, cell death, malondialdehyde contents and relative electrolyte leakage while a higher proline content and reactive oxygen species-scavenging enzyme activities was observed during stress conditions. Moreover, further investigation revealed that the expression levels of several stress-responsive genes were up regulated in drought-tolerant transgenic rice plants, compared with those in wild type plants. In addition to the drought tolerance, the AtWRKY57 over-expressing plants also had enhanced salt and PEG stress tolerances. Taken together, our study indicates that over-expressing AtWRKY57 in rice improved not only drought tolerance but also salt and PEG tolerance, demonstrating its potential role in crop improvement. PMID- 26904093 TI - Increasing Metagenomic Resolution of Microbiome Interactions Through Functional Phylogenomics and Bacterial Sub-Communities. AB - The genomic composition of the microbiome and its relationship with the environment is an exciting open question in biology. Metagenomics is a useful tool in the discovery of previously unknown taxa, but its use to understand the functional and ecological capacities of the microbiome is limited until taxonomy and function are understood in the context of the community. We suggest that this can be achieved using a combined functional phylogenomics and co-culture-based experimental strategy that can increase our capacity to measure sub-community interactions. Functional phylogenomics can identify and partition the genome such that hidden gene functions and gene clusters with unique evolutionary signals are revealed. We can test these phylogenomic predictions using an experimental model based on sub-community populations that represent a subset of the diversity directly obtained from environmental samples. These populations increase the detection of mechanisms that drive functional forces in the assembly of the microbiome, in particular the role of metabolites from key taxa in community interactions. Our combined approach leverages the potential of metagenomics to address biological questions from ecological systems. PMID- 26904092 TI - Systemic Induction of NO-, Redox-, and cGMP Signaling in the Pumpkin Extrafascicular Phloem upon Local Leaf Wounding. AB - Cucurbits developed the unique extrafascicular phloem (EFP) as a defensive structure against herbivorous animals. Mechanical leaf injury was previously shown to induce a systemic wound response in the EFP of pumpkin (Cucurbita maxima). Here, we demonstrate that the phloem antioxidant system and protein modifications by NO are strongly regulated during this process. Activities of the central antioxidant enzymes dehydroascorbate reductase, glutathione reductase and ascorbate reductase were rapidly down-regulated at 30 min with a second minimum at 24 h after wounding. As a consequence levels of total ascorbate and glutathione also decreased with similar bi-phasic kinetics. These results hint toward a wound-induced shift in the redox status of the EFP. Nitric oxide (NO) is another important player in stress-induced redox signaling in plants. Therefore, we analyzed NO-dependent protein modifications in the EFP. Six to forty eight hours after leaf damage total S-nitrosothiol content and protein S-nitrosylation were clearly reduced, which was contrasted by a pronounced increase in protein tyrosine nitration. Collectively, these findings suggest that NO-dependent S nitrosylation turned into peroxynitrite-mediated protein nitration upon a stress induced redox shift probably involving the accumulation of reactive oxygen species within the EFP. Using the biotin switch assay and anti-nitrotyrosine antibodies we identified 9 candidate S-nitrosylated and 6 candidate tyrosine nitrated phloem proteins. The wound-responsive Phloem Protein 16-1 (PP16-1) and Cyclophilin 18 (CYP18) as well as the 26.5 kD isoform of Phloem Protein 2 (PP2) were amenable to both NO modifications and could represent important redox sensors within the cucurbit EFP. We also found that leaf injury triggered the systemic accumulation of cyclic guanosine monophosphate (cGMP) in the EFP and discuss the possible function of this second messenger in systemic NO and redox signaling within the EFP. PMID- 26904095 TI - Identification of Metabolic Pathway Systems. AB - The estimation of parameters in even moderately large biological systems is a significant challenge. This challenge is greatly exacerbated if the mathematical formats of appropriate process descriptions are unknown. To address this challenge, the method of dynamic flux estimation (DFE) was proposed for the analysis of metabolic time series data. Under ideal conditions, the first phase of DFE yields numerical representations of all fluxes within a metabolic pathway system, either as values at each time point or as plots against their substrates and modulators. However, this numerical result does not reveal the mathematical format of each flux. Thus, the second phase of DFE selects functional formats that are consistent with the numerical trends obtained from the first phase. While greatly facilitating metabolic data analysis, DFE is only directly applicable if the pathway system contains as many dependent variables as fluxes. Because most actual systems contain more fluxes than metabolite pools, this requirement is seldom satisfied. Auxiliary methods have been proposed to alleviate this issue, but they are not general. Here we propose strategies that extend DFE toward general, slightly underdetermined pathway systems. PMID- 26904094 TI - Comparison of Acceleration Techniques for Selected Low-Level Bioinformatics Operations. AB - Within the recent years clock rates of modern processors stagnated while the demand for computing power continued to grow. This applied particularly for the fields of life sciences and bioinformatics, where new technologies keep on creating rapidly growing piles of raw data with increasing speed. The number of cores per processor increased in an attempt to compensate for slight increments of clock rates. This technological shift demands changes in software development, especially in the field of high performance computing where parallelization techniques are gaining in importance due to the pressing issue of large sized datasets generated by e.g., modern genomics. This paper presents an overview of state-of-the-art manual and automatic acceleration techniques and lists some applications employing these in different areas of sequence informatics. Furthermore, we provide examples for automatic acceleration of two use cases to show typical problems and gains of transforming a serial application to a parallel one. The paper should aid the reader in deciding for a certain techniques for the problem at hand. We compare four different state-of-the-art automatic acceleration approaches (OpenMP, PluTo-SICA, PPCG, and OpenACC). Their performance as well as their applicability for selected use cases is discussed. While optimizations targeting the CPU worked better in the complex k-mer use case, optimizers for Graphics Processing Units (GPUs) performed better in the matrix multiplication example. But performance is only superior at a certain problem size due to data migration overhead. We show that automatic code parallelization is feasible with current compiler software and yields significant increases in execution speed. Automatic optimizers for CPU are mature and usually no additional manual adjustment is required. In contrast, some automatic parallelizers targeting GPUs still lack maturity and are limited to simple statements and structures. PMID- 26904096 TI - Editorial: Epigenetics as a Deep Intimate Dialogue between Host and Symbionts. PMID- 26904097 TI - The Importance of Critically Examining the Level of Propositions When Evaluating Forensic DNA Results. PMID- 26904099 TI - The MiRNA Journey from Theory to Practice as a CNS Biomarker. AB - MicroRNAs (miRNAs), small nucleotide sequences that control gene transcription, have the potential to serve an expanded function as indicators in the diagnosis and progression of neurological disorders. Studies involving debilitating neurological diseases such as, Alzheimer's disease, multiple sclerosis, traumatic brain injuries, Parkinson's disease and CNS tumors, already provide validation for their clinical diagnostic use. These small nucleotide sequences have several features, making them favorable candidates as biomarkers, including function in multiple tissues, stability in bodily fluids, a role in pathogenesis, and the ability to be detected early in the disease course. Cerebrospinal fluid, with its cell-free environment, collection process that minimizes tissue damage, and direct contact with the brain and spinal cord, is a promising source of miRNA in the diagnosis of many neurological disorders. Despite the advantages of miRNA analysis, current analytic technology is not yet affordable as a clinically viable diagnostic tool and requires standardization. The goal of this review is to explore the prospective use of CSF miRNA as a reliable and affordable biomarker for different neurological disorders. PMID- 26904100 TI - The Process of Analyzing Data is the Emergent Feature of Data Science. PMID- 26904098 TI - Hypothesis: Paralog Formation from Progenitor Proteins and Paralog Mutagenesis Spur the Rapid Evolution of Telomere Binding Proteins. AB - Through elegant studies in fungal cells and complex organisms, we propose a unifying paradigm for the rapid evolution of telomere binding proteins (TBPs) that associate with either (or both) telomeric DNA and telomeric proteins. TBPs protect and regulate telomere structure and function. Four critical factors are involved. First, TBPs that commonly bind to telomeric DNA include the c-Myb binding proteins, OB-fold single-stranded binding proteins, and G-G base paired Hoogsteen structure (G4) binding proteins. Each contributes independently or, in some cases, cooperatively, to provide a minimum level of telomere function. As a result of these minimal requirements and the great abundance of homologs of these motifs in the proteome, DNA telomere-binding activity may be generated more easily than expected. Second, telomere dysfunction gives rise to genome instability, through the elevation of recombination rates, genome ploidy, and the frequency of gene mutations. The formation of paralogs that diverge from their progenitor proteins ultimately can form a high frequency of altered TBPs with altered functions. Third, TBPs that assemble into complexes (e.g., mammalian shelterin) derive benefits from the novel emergent functions. Fourth, a limiting factor in the evolution of TBP complexes is the formation of mutually compatible interaction surfaces amongst the TBPs. These factors may have different degrees of importance in the evolution of different phyla, illustrated by the apparently simpler telomeres in complex plants. Selective pressures that can utilize the mechanisms of paralog formation and mutagenesis to drive TBP evolution along routes dependent on the requisite physiologic changes. PMID- 26904102 TI - Structural and Dynamic Characterization of the C313Y Mutation in Myostatin Dimeric Protein, Responsible for the "Double Muscle" Phenotype in Piedmontese Cattle. AB - The knowledge of the molecular effects of the C313Y mutation, responsible for the "double muscle" phenotype in Piedmontese cattle, can help understanding the actual mechanism of phenotype determination and paves the route for a better modulation of the positive effects of this economic important phenotype in the beef industry, while minimizing the negative side effects, now inevitably intersected. The structure and dynamic behavior of the active dimeric form of Myostatin in cattle was analyzed by means of three state-of-the-art Molecular Dynamics simulations, 200-ns long, of wild-type and C313Y mutants. Our results highlight a role for the conserved Arg333 in establishing a network of short and long range interactions between the two monomers in the wild-type protein that is destroyed upon the C313Y mutation even in a single monomer. Furthermore, the native protein shows an asymmetry in residue fluctuation that is absent in the double monomer mutant. Time window analysis on further 200-ns of simulation demonstrates that this is a characteristic behavior of the protein, likely dependent on long range communications between monomers. The same behavior, in fact, has already been observed in other mutated dimers. Finally, the mutation does not produce alterations in the secondary structure elements that compose the characteristic TGF-beta cystine-knot motif. PMID- 26904103 TI - Patch-Based Segmentation with Spatial Consistency: Application to MS Lesions in Brain MRI. AB - This paper presents an automatic lesion segmentation method based on similarities between multichannel patches. A patch database is built using training images for which the label maps are known. For each patch in the testing image, k similar patches are retrieved from the database. The matching labels for these k patches are then combined to produce an initial segmentation map for the test case. Finally an iterative patch-based label refinement process based on the initial segmentation map is performed to ensure the spatial consistency of the detected lesions. The method was evaluated in experiments on multiple sclerosis (MS) lesion segmentation in magnetic resonance images (MRI) of the brain. An evaluation was done for each image in the MICCAI 2008 MS lesion segmentation challenge. Results are shown to compete with the state of the art in the challenge. We conclude that the proposed algorithm for segmentation of lesions provides a promising new approach for local segmentation and global detection in medical images. PMID- 26904101 TI - Cellular Senescence as the Causal Nexus of Aging. AB - In this paper we present cellular senescence as the ultimate driver of the aging process, as a "causal nexus" that bridges microscopic subcellular damage with the phenotypic, macroscopic effect of aging. It is important to understand how the various types of subcellular damage correlated with the aging process lead to the larger, visible effects of anatomical aging. While it has always been assumed that subcellular damage (cause) results in macroscopic aging (effect), the bridging link between the two has been hard to define. Here, we propose that this bridge, which we term the "causal nexus", is in fact cellular senescence. The subcellular damage itself does not directly cause the visible signs of aging, but rather, as the damage accumulates and reaches a critical mass, cells cease to proliferate and acquire the deleterious "senescence-associated secretory phenotype" (SASP) which then leads to the macroscopic consequences of tissue breakdown to create the physiologically aged phenotype. Thus senescence is a precondition for anatomical aging, and this explains why aging is a gradual process that remains largely invisible during most of its progression. The subcellular damage includes shortening of telomeres, damage to mitochondria, aneuploidy, and DNA double-strand breaks triggered by various genetic, epigenetic, and environmental factors. Damage pathways acting in isolation or in concert converge at the causal nexus of cellular senescence. In each species some types of damage can be more causative than in others and operate at a variable pace; for example, telomere erosion appears to be a primary cause in human cells, whereas activation of tumor suppressor genes is more causative in rodents. Such species-specific mechanisms indicate that despite different initial causes, most of aging is traced to a single convergent causal nexus: senescence. The exception is in some invertebrate species that escape senescence, and in non-dividing cells such as neurons, where senescence still occurs, but results in the SASP rather than loss of proliferation plus SASP. Aging currently remains an inevitable endpoint for most biological organisms, but the field of cellular senescence is primed for a renaissance and as our understanding of aging is refined, strategies capable of decelerating the aging process will emerge. PMID- 26904105 TI - A Natural Language Interface Concordant with a Knowledge Base. AB - The discordance between expressions interpretable by a natural language interface (NLI) system and those answerable by a knowledge base is a critical problem in the field of NLIs. In order to solve this discordance problem, this paper proposes a method to translate natural language questions into formal queries that can be generated from a graph-based knowledge base. The proposed method considers a subgraph of a knowledge base as a formal query. Thus, all formal queries corresponding to a concept or a predicate in the knowledge base can be generated prior to query time and all possible natural language expressions corresponding to each formal query can also be collected in advance. A natural language expression has a one-to-one mapping with a formal query. Hence, a natural language question is translated into a formal query by matching the question with the most appropriate natural language expression. If the confidence of this matching is not sufficiently high the proposed method rejects the question and does not answer it. Multipredicate queries are processed by regarding them as a set of collected expressions. The experimental results show that the proposed method thoroughly handles answerable questions from the knowledge base and rejects unanswerable ones effectively. PMID- 26904104 TI - Caffeic Acid Phenethyl Ester Regulates PPAR's Levels in Stem Cells-Derived Adipocytes. AB - Hypertrophic obesity inhibits activation of peroxisome proliferators-activated receptor gamma (PPARgamma), considered the key mediator of the fully differentiated and insulin sensitive adipocyte phenotype. We examined the effects of Caffeic Acid Phenethyl Ester (Cape), isolated from propolis, a honeybee hive product, on Adipose Stem Cells (ASCs) differentiation to the adipocyte lineage. Finally we tested the effects of Cape on insulin-resistant adipocytes. Quantification of Oil Red O-stained cells showed that lipid droplets decreased following Cape treatment as well as radical oxygen species formation. Additionally, exposure of ASC to high glucose levels decreased adiponectin and increased proinflammatory cytokines mRNA levels, which were reversed by Cape mediated increase of insulin sensitivity. Cape treatment resulted in decreased triglycerides synthesis and increased beta-oxidation. Exposure of ASCs to Lipopolysaccharide (LPS) induced a reduction of PPARgamma, an increase of IL-6 levels associated with a well-known stimulation of lipolysis; Cape partially attenuated the LPS-mediated effects. These observations reveal the main role of PPARgamma in the adipocyte function and during ASC differentiation. As there is now substantial interest in functional food and nutraceutical products, the observed therapeutic value of Cape in insulin-resistance related diseases should be taken into consideration. PMID- 26904106 TI - Clinicoepidemiological Observational Study of Acquired Alopecias in Females Correlating with Anemia and Thyroid Function. AB - Alopecia can either be inherited or acquired; the latter, more common, can be diffuse, patterned, and focal, each having cicatricial and noncicatricial forms. This observational study of 135 cases in a semiurban Indian population aimed to detect the prevalence of various forms of acquired alopecia in females and correlate the same with levels of hemoglobin, serum ferritin, triiodothyronine, thyroxin, and thyroid stimulating hormone. The majority (84, 62.2%) of our cases of alopecia had telogen effluvium followed by female pattern alopecia (32, 23.7%). Stress (86, 63.7%), topical application of chemicals (72, 53.3%), systemic medications for concurrent illnesses (62, 5%), and pregnancy (14, 10.3%) were the common exacerbating factors. Neither low hemoglobin (<12 gm%, 73.4%) nor low serum ferritin (<12 MUg/L, 6.7%) was found to be statistically significant. A majority (90, 90.9%) of 99 cases with anemia (hemoglobin levels of <12 gm%) had serum ferritin levels >12 MUg/L. Though lack of vitamin B12 testing was a limitation of our study, its deficiency could be the probable cause of iron deficiency as the majority (58, 64.4%) of these cases, as indeed majority (89, 65.4%) of our study population, were vegetarians. Thyroid disorders (23, 17%, including 9 newly diagnosed) were not of significance statistically. PMID- 26904107 TI - Leprosy Continues to Occur in Hilly Areas of North India. AB - Background. The aim of present study was to describe the profile of leprosy patients attending the outpatient department of dermatology in tertiary care hospital in Srinagar, Uttarakhand, North India. Methodology. This descriptive retrospective study. Patient data at the time of diagnosis were retrieved onto a predesigned proforma, which concerned the following variables at the time of registration: age, sex, and residence. Newly registered outpatients leprosy cases between 2009 and 2014 were included in the study. Results. It was found that 65 were multibacillary leprosy cases. Males constituted 62.8% of all leprosy cases. The majority (83.7%) belonged to the age group of 18-60 years. Of the total 48.8% of the new leprosy cases were from the Pauri district. The leprosy incidence rate in this population was 2.71 per 1000 patients. Conclusion. Leprosy still continues to be a communicable disease of concern. The lower incidence in women and children provokes the need to strengthen contact screening, early case detection, and referral activities in the population to sustain elimination. PMID- 26904108 TI - A Comparison of Short- and Long-Term Therapeutic Outcomes of Infliximab- versus Tacrolimus-Based Strategies for Steroid-Refractory Ulcerative Colitis. AB - Background/Aims. Antitumor necrosis factor antibodies and calcineurin inhibitors have shown good therapeutic efficacy for steroid-refractory ulcerative colitis (UC). Although some studies have compared the efficacy of infliximab (IFX) and cyclosporin A, there are no published studies comparing IFX and tacrolimus (Tac). This study aimed to compare therapeutic efficacies between IFX- and Tac-based strategies for steroid-refractory UC. Methods. Between July 2009 and August 2013, 95 patients with steroid-refractory UC received either IFX (n = 48) or Tac (n = 47) in our hospital. In the IFX group, the patients continued to receive maintenance treatment with IFX. In the Tac group, patients discontinued Tac treatment up to 3 months and subsequently received thiopurine. We retrospectively compared the therapeutic outcomes between the groups. Results. There was no significant difference in the colectomy-free rate, clinical remission rate, and clinical response rate at 2 months between the groups. However, relapse-free survival was significantly higher in the IFX group than in the Tac group (p < 0.001; log-rank test). The proportions of serious adverse events did not differ between the groups. Conclusion. The findings of our study showed that IFX and Tac have similar short-term therapeutic efficacy for steroid-refractory UC. Maintenance treatment with IFX, however, yields better long-term outcomes than Tac-thiopurine bridging treatment. PMID- 26904109 TI - Prealbumin/CRP Based Prognostic Score, a New Tool for Predicting Metastasis in Patients with Inoperable Gastric Cancer. AB - Background. There is a considerable dissimilarity in the survival duration of the patients with gastric cancer. We aimed to assess the systemic inflammatory response (SIR) and nutritional status of these patients before the commencement of chemotherapy to find the appropriate prognostic factors and define a new score for predicting metastasis. Methods. SIR was assessed using Glasgow Prognostic Score (GPS). Then a score was defined as prealbumin/CRP based prognostic score (PCPS) to be compared with GPS for predicting metastasis and nutritional status. Results. 71 patients with gastric cancer were recruited in the study. 87% of patients had malnutrition. There was a statistical difference between those with metastatic (n = 43) and those with nonmetastatic (n = 28) gastric cancer according to levels of prealbumin and CRP; however they were not different regarding patient generated subjective global assessment (PG-SGA) and GPS. The best cut-off value for prealbumin was determined at 0.20 mg/dL and PCPS could predict metastasis with 76.5% sensitivity, 63.6% specificity, and 71.4% accuracy. Metastatic and nonmetastatic gastric cancer patients were different in terms of PCPS (P = 0.005). Conclusion. PCPS has been suggested for predicting metastasis in patients with gastric cancer. Future studies with larger sample size have been warranted. PMID- 26904110 TI - The Prevalence of Headache in Crohn's Disease: Single-Center Experience. AB - Objectives. This study is aimed at studying the prevalence and characteristics of different types of headaches in patients with Crohn's disease. Materials and Methods. 51 patients in Crohn's disease group (F/M: 26/25) and 51 patients in control group (F/M: 27/24) were involved. Patients in Crohn's disease group were diagnosed and monitored according to European Crohn's and Colitis Organization diagnostic criteria. The control group composed of healthy subjects with similar age and sex to Crohn's disease group. Headache was classified using the International Headache Society II criteria. Results. Headache was reported by 35/51 (68.6%) patients in Crohn's disease group and 21/51 (41.2%) patients in the control group. The prevalence of headache was statistically high in the group with Crohn's disease (OR: 3.125 (95% CI: 1.38-7.04); p = 0.01). Comparing two groups with respect to their subtypes of headaches resulted in that the tension type headache was statistically (p = 0.008) higher in Crohn's disease group (26/51) than in the control group (12/51). However, no significant difference was found in the migraine-type headache (p = 1). Conclusions. This study indicates that the prevalence of headache is high in patients with Crohn's disease and most commonly associated with the tension-type headache. PMID- 26904111 TI - High Prevalence of Human Papillomavirus in Colorectal Cancer in Hispanics: A Case Control Study. AB - The role of Human Papillomavirus (HPV) in colorectal carcinogenesis remains elusive. Based on the high incidence of HPV-associated malignancies among Puerto Rican Hispanics, this study aimed to assess the prevalence of HPV infection and viral integration in colorectal tissues in order to evaluate its putative role in colorectal cancer (CRC). In this case-control study, the prevalence of HPV infection in CRC (cases n = 45) and normal colon mucosa from cancer-free subjects (controls n = 36) was assessed by a nested PCR strategy. HPV-16 genotyping was performed in HPV-positive tissues and the physical status of the HPV-16 genome was determined by E2 detection. HPV was detected in 19 of 45 (42.2%) CRC cases (mean age 61.1 +/- 10.7 years, 24 males) and in 1 of 36 (2.8%) controls (mean age 60.9 +/- 9.6 years, 24 males) with an OR = 25.58 (95% CI 3.21 to 203.49). HPV-16 was detected in 63.2% of the HPV-positive colorectal tumors; genome integration was observed in all HPV-16 positive cases. This is the first report showing the high prevalence of HPV infections in Caribbean Hispanic colorectal tumors. Despite evidence of HPV integration into the host genome, further mechanistic analysis examining HPV oncoprotein expression and the putative role of these oncoproteins in colorectal carcinogenesis is warranted. PMID- 26904113 TI - Effects of Curcumin on Parameters of Myocardial Oxidative Stress and of Mitochondrial Glutathione Turnover in Reoxygenation after 60 Minutes of Hypoxia in Isolated Perfused Working Guinea Pig Hearts. AB - In cardiovascular surgery ischemia-reperfusion injury is a challenging problem, which needs medical intervention. We investigated the effects of curcumin on cardiac, myocardial, and mitochondrial parameters in perfused isolated working Guinea pig hearts. After preliminary experiments to establish the model, normoxia was set at 30 minutes, hypoxia was set at 60, and subsequent reoxygenation was set at 30 minutes. Curcumin was applied in the perfusion buffer at 0.25 and 0.5 MUM concentrations. Cardiac parameters measured were afterload, coronary and aortic flows, and systolic and diastolic pressure. In the myocardium histopathology and AST in the perfusate indicated cell damage after hypoxia and malondialdehyde (MDA) levels increased to 232.5% of controls during reoxygenation. Curcumin protected partially against reoxygenation injury without statistically significant differences between the two dosages. Mitochondrial MDA was also increased in reoxygenation (165% of controls), whereas glutathione was diminished (35.2%) as well as glutathione reductase (29.3%), which was significantly increased again to 62.0% by 0.05 MUM curcumin. Glutathione peroxidase (GPx) was strongly increased in hypoxia and even more in reoxygenation (255% of controls). Curcumin partly counteracted this increase and attenuated GPx activity independently in hypoxia and in reoxygenation, 0.25 MUM concentration to 150% and 0.5 MUM concentration to 200% of normoxic activity. PMID- 26904112 TI - The Association between Helicobacter pylori Infection and Chronic Hepatitis C: A Meta-Analysis and Trial Sequential Analysis. AB - Purpose. Helicobacter pylori is a common gastric disease-inducing pathogen. Although an increasing number of recent studies have shown that H. pylori is a risk factor for liver disease, the potential association between H. pylori infection and chronic hepatitis C still remains controversial. The aim of our meta-analysis was to evaluate a potential association between H. pylori infection and chronic hepatitis C. Methods. We searched the PubMed, Embase, CNKI, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases between January 1, 1994, and May 1, 2015. Results. This study included a total of 1449 patients with chronic hepatitis C and 2377 control cases. The prevalence of H. pylori was significantly higher in patients with chronic hepatitis C than in those without chronic hepatitis C. The pooled odds ratio was 2.93. In a subgroup analysis, the odds ratios were 4.48 for hepatitis C virus- (HCV-) related cirrhosis and 5.45 for hepatocellular carcinoma. Conclusion. Our study found a strong association between H. pylori and chronic hepatitis C, particularly during the HCV progression stage; thus, we recommend active screening for H. pylori in patients with chronic hepatitis C. PMID- 26904114 TI - The Influence of Differences in Solvents and Concentration on the Efficacy of Propofol at Induction of Anesthesia. AB - Background. Propofol is a popular intravenous anesthetic and varieties of formulations were produced from different laboratories. The present study compared efficacy of propofol of different laboratories and different concentrations (1 and 2%) during induction of anesthesia. Methods. Seventy-five scheduled surgical patients were randomly allocated into three groups. The patients of group D1 received AstraZeneca Diprivan 1% (Osaka, Japan) at a rate of 40 mg kg(-1) h(-1). Group M1 was given 1% Maruishi (Maruishi Pharmaceutical, Osaka, Japan) and group M2 was given 2% formulation at the same rate of propofol. Achieving hypnosis was defined as failure to open their eyes in response to a verbal command and the venous blood sample was withdrawn. Results. The hypnotic doses of M2 were significantly larger (D1: 91.4 +/- 30.9, M1: 90.7 +/- 26.7, and M2: 118.4 +/- 40.2 mg, resp. (mean +/- SD). p < 0.005). Age and gender were selected as statistically significant covariates using general linear model ANOVA. The blood concentration showed no significant difference among the groups (3.73 +/- 2.34, 4.10 +/- 3.04, and 4.70 +/- 2.12 MUg mL(-1), resp.). Conclusion. The required dose of propofol was different among the formulations; however, the serum concentration showed no significant difference. This trial is registered with UMIN Clinical Trial Registry: UMIN000019925. PMID- 26904115 TI - Medical Device-Associated Candida Infections in a Rural Tertiary Care Teaching Hospital of India. AB - Health care associated infections (HCAIs) add incrementally to the morbidity, mortality, and cost expected of the patient's underlying diseases alone. Approximately, about half all cases of HCAIs are associated with medical devices. As Candida medical device-associated infection is highly drug resistant and can lead to serious life-threatening complications, there is a need of continuous surveillance of these infections to initiate preventive and corrective measures. The present study was conducted at a rural tertiary care hospital of India with an aim to evaluate the rate of medical device-associated Candida infections. Three commonly encountered medical device-associated infections (MDAI), catheter associated urinary tract infection (CA-UTI), intravascular catheter-related blood stream infections (CR-BSI), and ventilator-associated pneumonia (VAP), were targeted. The overall rate of MDAI in our hospital was 2.1 per 1000 device days. The rate of Candida related CA-UTI and CR-BSI was noted as 1.0 and 0.3, respectively. Untiring efforts taken by team members of Hospital Acquired Infection Control Committee along with maintenance of meticulous hygiene of the hospital and wards may explain the low MDAI rates in our institute. The present surveillance helped us for systematic generation of institutional data regarding MDAI with special reference to role of Candida spp. PMID- 26904116 TI - Ulcerative Colitis and Its Association with Salmonella Species. AB - Ulcerative colitis (UC) is characterized by presence of ulcer in colon and bloody diarrhea. The present study explores the possibility of association between Salmonella and ulcerative colitis. The present study comprised 59 cases of UC, 28 of colon cancer (CC), 127 of irritable bowel syndrome (IBS), and 190 of healthy control. The serological study was done by Widal and Indirect Haemagglutination Assay (IHA) for ViAb. Nested PCR was performed targeting fliC, staA, and stkG gene for Typhi and Paratyphi A, respectively. A total of 15.3% patients were positive for Salmonella "O" antigen among them 18.6% UC, 35.5% CC, 12.6% IBS, and 15.3% healthy control. A total of 36.9% patients were positive for "H" antigen including 39.0%, 57.1%, and 67.7% UC, CC, and IBS, respectively. About 1.73% show positive agglutination for AH antigen including 3.4%, 3.6%, and 1.6%, UC, CC, and IBS. A total of 10.89% were positive for ViAb. While 6.8% of UC, 10.7% of CC, 11.0% of IBS, and 12.1% of healthy subjects were positive for the antibody, the PCR positivity rates for Salmonella specific sequences were 79.7% in UC, 53.6% in CC, 66.1% in IBS, and 16.3% in healthy controls. The present study suggested that higher prevalence of Salmonella might play important role in etiopathogenesis of UC, IBS, and CC. PMID- 26904117 TI - Possible Protective Effect of Diacerein on Doxorubicin-Induced Nephrotoxicity in Rats. AB - Nephrotoxicity is one of the limiting factors for using doxorubicin (DOX). Interleukin 1 has major role in DOX-induced nephrotoxicity, so we investigated the effect of interleukin 1 receptor antagonist diacerein (DIA) on DOX-induced nephrotoxicity. DIA (25 and 50 mg/kg/day) was administered orally to rats for 15 days, in the presence or absence of nephrotoxicity induced by a single intraperitoneal injection of DOX (15 mg/kg) at the 11th day. We measured levels of serum urea, creatinine, renal reduced glutathione (GSH), malondialdehyde (MDA), total nitrites (NO x ), catalase, and superoxide dismutase (SOD). In addition, caspase-3, tumor necrosis factor alpha (TNFalpha), nuclear factor kappa B (NFkappaB) expressions, and renal histopathology were assessed. Our results showed that DOX-induced nephrotoxicity was ameliorated or reduced by both doses of DIA, but diacerein high dose (DHD) showed more improvement than diacerein low dose (DLD). This protective effect was manifested by significant improvement in all measured parameters compared to DOX treated group by using DHD. DLD showed significant improvement of creatinine, MDA, NO x , GSH, histopathology, and immunohistochemical parameters compared to DOX treated group. PMID- 26904118 TI - The Impact and Successes of a Paediatric Endocrinology Fellowship Program in Africa. AB - Background. The prevalence and distribution of endocrine disorders in children in Africa are not well known because most cases are often undiagnosed or diagnosed too late. The awareness of this led to the launch of the Paediatric Endocrinology Training Center for Africa (PETCA) designed to improve quality and access to health care by training paediatricians from Africa in paediatric endocrinology. Methods. The fellowship is undertaken over an 18-month period: six months of clinical and theoretical training in Kenya, nine months of project research at the fellow's home country, and three months of consolidation in Kenya. Upon completion, certified paediatricians are expected to set up centers of excellence. Results. There have been two phases, phase I from January 2008 to October 2012 and phase II from January 2012 to April 2015. Fifty-four fellows from 12 African countries have been certified, 34 (phase I) and 20 (phase II). Over 1,000 patients with wide ranging diabetes and endocrine disorders have been diagnosed and treated and are being followed up at the centers of excellence. Conclusion. The successes of the PETCA initiative demonstrate the impact a capacity building and knowledge transfer model can have on people in resource poor settings using limited resources. PMID- 26904119 TI - Prenatal and Childhood Growth, Chemerin Concentrations, and Metabolic Health in Adult Life. AB - Several noncommunicable diseases have their origins in early developmental phases. One factor possibly explaining the association between early growth and later health could be adipocyte function. The objective of this study was to assess the association between the adipocytokine chemerin and early growth and later health. 1074 participants from Helsinki Birth Cohort Study born 1934-1944 with information on prenatal and childhood growth participated. Metabolic outcomes include glucose tolerance, adiposity, and chemerin concentration. Mean chemerin concentrations were 5.0 ng/mL higher in women than in men (95% CI 2.7 to 7.2, p < 0.001). The strongest correlate of chemerin concentration was adult waist circumference and body fat percentage (r = 0.22, p < 0.001 and r = 0.21, p < 0.001, resp.). After adjustment for body fat percentage, chemerin concentration was 5.4 ng/mL lower in subjects with type 2 diabetes than in those with normal glucose tolerance (-0.2 to 10.9, p = 0.06). It was 3.0 ng/mL higher in those with metabolic syndrome than in those without (0.6 to 5.3, p = 0.01). No measure of early growth was associated with chemerin concentration. Our findings do not support a role for chemerin in linking early growth with later metabolic health. PMID- 26904121 TI - A Three-Dimensional Finite Element Study on the Biomechanical Simulation of Various Structured Dental Implants and Their Surrounding Bone Tissues. AB - Background/Purpose. This three-dimensional finite element study observed the stress distribution characteristics of 12 types of dental implants and their surrounding bone tissues with various structured abutments, implant threads, and healing methods under different amounts of concentrated loading. Materials and Methods. A three-dimensional geometrical model of a dental implant and its surrounding bone tissue was created; the model simulated a screw applied with a preload of 200 N or a torque of 0.2 N.m and a prosthetic crown applied with a vertical or an inclined force of 100 N. The Von Mises stress was evaluated on the 12 types of dental implants and their surrounding bone tissues. Results. Under the same loading force, the stress influence on the implant threads was not significant; however, the stress influence on the cancellous bone was obvious. The stress applied to the abutment, cortical bone, and cancellous bone by the inclined force applied to the crown was larger than the stress applied by the vertical force to the crown, and the abutment stress of the nonsubmerged healing implant system was higher than that of the submerged healing implant system. Conclusion. A dental implant system characterised by a straight abutment, rectangle tooth, and nonsubmerged healing may provide minimum value for the implant-bone interface. PMID- 26904120 TI - Impact of Orthodontic Treatment on Periodontal Tissues: A Narrative Review of Multidisciplinary Literature. AB - The aim of this review is to describe the most commonly observed changes in periodontium caused by orthodontic treatment in order to facilitate specialists' collaboration and communication. An electronic database search was carried out using PubMed abstract and citation database and bibliographic material was then used in order to find other appropriate sources. Soft and hard periodontal tissues changes during orthodontic treatment and maintenance of the patients are discussed in order to provide an exhaustive picture of the possible interactions between these two interwoven disciplines. PMID- 26904123 TI - Myeloablative Conditioning with PBSC Grafts for T Cell-Replete Haploidentical Donor Transplantation Using Posttransplant Cyclophosphamide. AB - Relapse is the main cause of treatment failure after nonmyeloablative haploidentical transplant (haplo-HSCT). In an attempt to reduce relapse, we have developed a myeloablative (MA) haplo-HSCT approach utilizing posttransplant cyclophosphamide (PT/Cy) and peripheral blood stem cells as the stem cell source. We summarize the results of two consecutive clinical trials, using a busulfan based (n = 20) and a TBI-based MA preparative regimen (n = 30), and analyze a larger cohort of 64 patients receiving MA haplo-HSCT. All patients have engrafted with full donor chimerism and no late graft failures. Grade III-IV acute GVHD and moderate-severe chronic GVHD occurred in 23% and 30%, respectively. One-year NRM was 10%. Predicted three-year overall survival, disease-free survival, and relapse were 53%, 53%, and 26%, respectively, in all patients and 79%, 74%, and 9%, respectively, in patients with a low/intermediate disease risk index (DRI). In multivariate analysis, DRI was the most significant predictor of survival and relapse. Use of TBI (versus busulfan) had no significant impact on survival but was associated with significantly less BK virus-associated hemorrhagic cystitis. We contrast our results with other published reports of MA haplo-HSCT PT/Cy in the literature and attempt to define the comparative utility of MA haplo-HSCT to other methods of transplantation. PMID- 26904122 TI - Donor Specific Anti-HLA Antibody and Risk of Graft Failure in Haploidentical Stem Cell Transplantation. AB - Outcomes of allogeneic hematopoietic stem cell transplantation (AHSCT) using HLA half matched related donors (haploidentical) have recently improved due to better control of alloreactive reactions in both graft-versus-host and host-versus-graft directions. The recognition of the role of humoral rejection in the development of primary graft failure in this setting has broadened our understanding about causes of engraftment failure in these patients, helped us better select donors for patients in need of AHSCT, and developed rational therapeutic measures for HLA sensitized patients to prevent this unfortunate event, which is usually associated with a very high mortality rate. With these recent advances the rate of graft failure in haploidentical transplantation has decreased to less than 5%. PMID- 26904124 TI - Comparison of Procleix Ultrio Elite and Procleix Ultrio NAT Assays for Screening of Transfusion Transmitted Infections among Blood Donors in India. AB - Background. Introduction of nucleic acid testing (NAT) has helped in decreasing window period donations, resulting in increased safety of blood supplies. NAT combines the advantages of direct and highly sequence-specific detection of viral genomes. We analysed the performance of newer Procleix Ultrio Elite (PUE) and Procleix Ultrio assay (PUA) for the screening of the viral markers in our donor population. Material and Methods. 10,015 donor samples were screened by routine immunoassays and both versions of NAT. NAT yields detected were subjected to viral load estimation and to other serological markers. Results. A total of 21 NAT yields were detected; three were positive by both NAT systems, whereas 18 samples were reactive by PUE only. NAT yields include 18 HBV and 3 HCV yields, of which 17 HBV yields were occult infections and 1 was window period (WP) infection. All 3 HCV yields were WP infections. No HIV-1/HIV-2 yield was found. Conclusion. Efficient target capture chemistry in the new TMA assay version significantly improved sensitivity. NAT is superior to serological immunoassays for screening of the viral markers; and the efficient target capture system in the newer TMA assay, namely, the PUE system, has significantly improved sensitivity over the earlier versions. PMID- 26904125 TI - Antibiotic-Resistant Bacteria Are Major Threats of Otitis Media in Wollo Area, Northeastern Ethiopia: A Ten-Year Retrospective Analysis. AB - Antibiotic resistance is an increasingly serious threat to human health that needs an urgent action. The aim of this study was to determine the prevalence and antibiotic susceptibility profiles of bacteria isolated from patient ear discharges suspected of otitis media. A retrospective analysis was performed using culture and antibiotic susceptibility test results of 1225 patients who visited Dessie Regional Health Research Laboratory from 2001 to 2011. Results showed a strong association (P < 0.001) between age and the risk of acquiring middle ear infection. The predominant bacterial isolates were Proteus spp. (28.8%), Staphylococcus aureus (23.7%), and Pseudomonas spp. (17.2%). Most of the isolated bacteria showed high resistance to ampicillin (88.5%), ceftriaxone (84.5%), amoxicillin (81.9%), and tetracycline (74.5%). About 72.5% of Proteus spp. and 62.2% of Pseudomonas spp. have developed resistance to one and more antibiotics used to treat them. This retrospective study also revealed the overall antibiotic resistance rate of bacterial isolates was increased nearly twofold (P = 0.001) over the last decade. Relatively, ciprofloxacin and gentamicin were the most effective antibiotics against all the isolates. In conclusion, antibiotic-resistant bacteria are alarmingly increasing in Wollo area, northeastern Ethiopia, and becoming a major public health problem in the management of patients with middle ear infection. PMID- 26904126 TI - Inferior Turbinate Size and CPAP Titration Based Treatment Pressures: No Association Found among Patients Who Have Not Had Nasal Surgery. AB - Objective. To evaluate the effect of turbinate sizes on the titrated continuous positive airway pressure (CPAP) therapeutic treatment pressures for patients with obstructive sleep apnea (OSA) who have not had nasal surgery. Study Design. Retrospective case series. Methods. A chart review was performed for 250 consecutive patients. Results. 45 patients met inclusion criteria. The mean +/- standard deviation (M +/- SD) for age was 54.6 +/- 22.4 years and for body mass index was 28.5 +/- 5.9 kg/m(2). The Spearman's rank correlation coefficient (r s ) between CPAP therapeutic treatment pressures and several variables were calculated and were weakly correlated (age r s = 0.29, nasal obstruction r s = 0.30), moderately correlated (body mass index r s = 0.42 and lowest oxygen saturation r s = -0.47), or strongly correlated (apnea-hypopnea index r s = 0.60 and oxygen desaturation index (r s = 0.62)). No statistical significance was found with one-way analysis of variance (ANOVA) between CPAP therapeutic treatment pressures and inferior turbinate size (right turbinates p value = 0.2012, left turbinate p value = 0.3064), nasal septal deviation (p value = 0.4979), or mask type (p value = 0.5136). Conclusion. In this study, CPAP titration based therapeutic treatment pressures were not found to be associated with inferior turbinate sizes; however, the CPAP therapeutic treatment pressures were strongly correlated with apnea-hypopnea index and oxygen desaturation index. PMID- 26904127 TI - Vestibular Disorders after Stapedial Surgery in Patients with Otosclerosis. AB - Introduction and Objectives. Vertigo is a described complication of stapedial surgery. Many studies have been conducted to assess the improvement of hearing loss, but there are few studies that assess vestibular function after stapedial surgery. The aim of this study was to evaluate the presence and characterize the vertigo after stapedial surgery. Methods. We conducted a prospective observational study. Patients undergoing stapedial surgery in our hospital between October 2013 and December 2014 were invited to participate. The vertigo was assessed before and 4 months after surgery, using the Dizziness Handicap Inventory. Results. We included 140 patients in the study. 12 patients (8.6%) reported vertigo before surgery, and all of them denied vertigo after surgery. 36 patients (25.7%) reported vertigo four months after surgery, and none of them had vertigo before surgery. Postoperative total scores in patients with vertigo ranged between 2 and 18 points. Conclusion. The study shows that vestibular disorders may remain after the immediate postoperative period and reinforces the need for clarification of the patient in the informed consent act. PMID- 26904128 TI - Rare Intracardiac Tumor: Primary Cardiac Lymphoma Presenting as Atypical Angina. AB - Primary lymphomas of the heart are extremely rare, accounting for 2% of all primary cardiac tumors. Due to the rare presentation, there is no proper consensus available on treatment strategy. Preoperative confirmation of the pathology is fundamental in guiding an early treatment plan, which allows for improved prognosis. Unfortunately, in most cases, primary cardiac lymphoma is only identified on postoperative histopathological analyses, which affect the treatment plan and outcome. Here, we report a unique case of primary cardiac lymphoma presented with dyspnea and reduced effort tolerance. Young age, rapid onset of symptom, and absence of cardiac risk factors prompted us towards further imaging and emergency resection. The patient received a course of postoperative chemotherapy and was disease-free on six months of follow-up. PMID- 26904129 TI - Chemokine (C-X-C) Ligand 12 Facilitates Trafficking of Donor Spermatogonial Stem Cells. AB - The chemokine (C-X-C) receptor type 4 (CXCR4) is an early marker of primordial germ cells (PGCs) essential for their migration and colonization of the gonads. In spermatogonial stem cells (SSCs), the expression of CXCR4 is promoted by the self-renewal factor, glial cell line-derived neurotrophic factor (GDNF). Here, we demonstrate an important role of CXCR4 during donor mouse SSCs reoccupation of the endogenous niche in recipient testis. Silencing of CXCR4 expression in mouse SSCs dramatically reduced the number of donor stem cell-derived colonies, whereas colony morphology and spermatogenesis were comparable to controls. Inhibition of CXCR4 signaling using a small molecule inhibitor (AMD3100) during the critical window of homing also significantly lowered the efficiency of donor-derived SSCs to establish spermatogenic colonies in recipient mice; however, the self-renewal of SSCs was not affected by exposure to AMD3100. Rather, in vitro migration assays demonstrate the influence of CXCR4-CXCL12 signaling in promoting germ cell migration. Together, these studies suggest that CXCR4-CXCL12 signaling functions to promote homing of SSCs towards the stem cell niche and plays a critical role in reestablishing spermatogenesis. PMID- 26904131 TI - Downregulation of the Yes-Associated Protein Is Associated with Extracellular Matrix Disorders in Ascending Aortic Aneurysms. AB - Previous studies indicate that extracellular matrix (ECM) disorders lead to the apoptosis of Vascular Smooth Muscle Cells (VSMCs), which impairs the aortic wall by reducing the generation of elastic fibers, and ultimately result in ascending aortic aneurysm. The critical role of the Yes-associated protein (YAP) has been elucidated in cardiac/SMC proliferation during cardiovascular development. However, the association of YAP expression and extracellular matrix disorders in ascending aortic aneurysms is not clear. Here, we present for the first time that the downregulation of YAP in VSMCs is associated with ECM disorders of the media in ascending aortic aneurysms. We found that aortic ECM deteriorated with increased apoptotic VSMCs. Moreover, expression of YAP was dramatically reduced in the aortic walls of patients with ascending aortic aneurysms, while the normal aortic samples exhibited abundant YAP in the VSMCs. These results suggest that downregulation of YAP leads to apoptosis of VSMCs, which are essential for the homeostasis of the aortic wall. The resultant ECM disorders affect aortic structure and function and contribute to the development of ascending aortic aneurysms. In summary, through assessment of clinical samples, we revealed the association between downregulation of YAP in VSMCs and the development of ascending aortic aneurysms, providing new insight into the pathogenesis of this disease. PMID- 26904130 TI - Stem Cell-Derived Exosomes: A Potential Alternative Therapeutic Agent in Orthopaedics. AB - Within the field of regenerative medicine, many have sought to use stem cells as a promising way to heal human tissue; however, in the past few years, exosomes (packaged vesicles released from cells) have shown more exciting promise. Specifically, stem cell-derived exosomes have demonstrated great ability to provide therapeutical benefits. Exosomal products can include miRNA, other genetic products, proteins, and various factors. They are released from cells in a paracrine fashion in order to combat local cellular stress. Because of this, there are vast benefits that medicine can obtain from stem cell-derived exosomes. If exosomes could be extracted from stem cells in an efficient manner and packaged with particular regenerative products, then diseases such as rheumatoid arthritis, osteoarthritis, bone fractures, and other maladies could be treated with cell-free regenerative medicine via exosomes. Many advances must be made to get to this point, and the following review highlights the current advances of stem cell-derived exosomes with particular attention to regenerative medicine in orthopaedics. PMID- 26904132 TI - Epigenetic Regulation Shapes the Stem Cells State. PMID- 26904135 TI - Neonatal Tetanus Immunity in Nigeria: The Effect of HIV Infection on Serum Levels and Transplacental Transfer of Antibodies. AB - Background. Tetanus toxoid immunisation of pregnant mother has remained the most effective strategy in eliminating neonatal tetanus. Impaired production and/or transplacental transfer of antibodies may affect the effectiveness of this strategy. We studied the effect of maternal HIV infection on serum levels and transplacental transfer of anti-tetanus antibodies. Methods. A total of 162 mother-baby paired serum samples were taken and analysed for anti-tetanus antibody levels using ELISA. Maternal HIV status was also determined by double ELISA technique. Maternal TT vaccination status was also documented. Results. Thirty-eight (23.5%) mothers and 41 (25.3%) babies were seronegative, out of whom 8 mothers were HIV positive and 9 babies were HIV exposed. HIV infected mothers and HIV exposed infants were, respectively, 16.27 times (OR = 16.27, 95% CI = 3.28 to 80.61) and 33.75 times (OR = 33.75, 95% CI = 4.12 to 276.40) more likely to be seronegative for anti-tetanus antibody. Similarly, HIV positive mother newborn pairs were 7.46 times more likely to have a poor transplacental transfer of tetanus antibodies (OR = 7.46, 95% CI = 1.96 to 28.41). Conclusions. Maternal HIV infection is associated with impaired maternofoetal transfer of anti-tetanus antibodies and seronegativity among mothers and their newborns. Hence, this may hinder efforts to eliminate neonatal tetanus. PMID- 26904134 TI - The Effect of Aqueous Extract of Cinnamon on the Metabolome of Plasmodium falciparum Using (1)HNMR Spectroscopy. AB - Malaria is responsible for estimated 584,000 deaths in 2013. Researchers are working on new drugs and medicinal herbs due to drug resistance that is a major problem facing them; the search is on for new medicinal herbs. Cinnamon is the bark of a tree with reported antiparasitic effects. Metabonomics is the simultaneous study of all the metabolites in biological fluids, cells, and tissues detected by high throughput technology. It was decided to determine the mechanism of the effect of aqueous extract of cinnamon on the metabolome of Plasmodium falciparum in vitro using (1)HNMR spectroscopy. Prepared aqueous extract of cinnamon was added to a culture of Plasmodium falciparum 3D7 and its 50% inhibitory concentration determined, and, after collection, their metabolites were extracted and (1)HNMR spectroscopy by NOESY method was done. The spectra were analyzed by chemometric methods. The differentiating metabolites were identified using Human Metabolome Database and the metabolic cycles identified by Metaboanalyst. 50% inhibitory concentration of cinnamon on Plasmodium falciparum was 1.25 mg/mL with p < 0.001. The metabolites were identified as succinic acid, glutathione, L-aspartic acid, beta-alanine, and 2-methylbutyryl glycine. The main metabolic cycles detected were alanine and aspartame and glutamate pathway and pantothenate and coenzyme A biosynthesis and lysine biosynthesis and glutathione metabolism, which are all important as drug targets. PMID- 26904133 TI - Endothelial Plasticity: Shifting Phenotypes through Force Feedback. AB - The endothelial lining of the vasculature is exposed to a large variety of biochemical and hemodynamic stimuli with different gradients throughout the vascular network. Adequate adaptation requires endothelial cells to be highly plastic, which is reflected by the remarkable heterogeneity of endothelial cells in tissues and organs. Hemodynamic forces such as fluid shear stress and cyclic strain are strong modulators of the endothelial phenotype and function. Although endothelial plasticity is essential during development and adult physiology, proatherogenic stimuli can induce adverse plasticity which contributes to disease. Endothelial-to-mesenchymal transition (EndMT), the hallmark of endothelial plasticity, was long thought to be restricted to embryonic development but has emerged as a pathologic process in a plethora of diseases. In this perspective we argue how shear stress and cyclic strain can modulate EndMT and discuss how this is reflected in atherosclerosis and pulmonary arterial hypertension. PMID- 26904136 TI - Allergic Fungal Rhinosinusitis: A Study in a Tertiary Care Hospital in India. AB - The study was conducted to study the occurrence and clinical presentation of allergic fungal rhinosinusitis (AFRS), characterize the same, and correlate with the microbiological profile. Clinically suspected cases of fungal rhinosinusitis (FRS) depending upon their clinical presentation, nasal endoscopy, and radiological evidences were included. Relevant clinical samples were collected and subjected to direct microscopy and culture and histopathological examination. 35 patients were diagnosed to have AFRS. The average age was 28.4 years with a range of 18-48 years. Allergic mucin was seen in all the AFRS patients but fungal hyphae were detected in only 20%. 80% of cases were positive for IgE. All the patients had nasal obstruction followed by nasal discharge (62.8%). Polyps were seen in 95% (unilateral (48.57%) and bilateral (45.71%)), deviated nasal septum was seen in 28.57%, and greenish yellow secretion was seen in 17.14%. Direct microscopy and septate hyphae were positive in 71.42% of cases. 91.4% of cases were positive by culture. 5.7% yielded mixed growth of A. flavus and A. niger. Prompt clinical suspicion with specific signs and symptoms along with timely sampling of the adequate patient specimens and the optimal and timely processing by microscopy and culture and histopathological examination is a must for early diagnosis and management. PMID- 26904137 TI - Noise Exposure and Hearing Capabilities of Quarry Workers in Ghana: A Cross Sectional Study. AB - INTRODUCTION: Although quarry operations have high economic significance, the effects they cause to the workers in terms of excessive noise production cannot be overlooked. This cross-sectional study assessed the extent of noise exposure and its influence on hearing capabilities among quarry workers in Ashanti region. METHODS: The study involved 400 workers randomly selected from five quarries in Ashanti region from April to June 2012. Data was collected using structured questionnaires, physical examination, and audiological assessments. A logistic regression model was fitted to assess independent predictors of hearing loss. RESULTS: All the machines used at the various quarries produced noise that exceeded the minimum threshold with levels ranging from 85.5 dBA to 102.7 dBA. 176 (44%) of study respondents had hearing threshold higher than 25 dBA. 18% and 2% of these were moderately (41-55 dBA) and severely (71-90 dBA) impaired, respectively. Age, duration of work, and use of earplugs independently predicted the development of hearing loss. Use of earplugs showed a protective effect on the development of hearing loss (OR = 0.45; 95% CI = 0.25, 0.84). CONCLUSION: This study provides empirical evidence on the extent of damage caused to quarry workers as a result of excessive noise exposure. This will support the institution of appropriate protective measures to minimize this threat. PMID- 26904138 TI - Computational Models of Ventilator Induced Lung Injury and Surfactant Dysfunction. AB - Managing acute respiratory distress syndrome (ARDS) invariably involves the administration of mechanical ventilation, the challenge being to avoid the iatrogenic sequellum known as ventilator-induced lung injury (VILI). Devising individualized ventilation strategies in ARDS requires that patient-specific lung physiology be taken into account, and this is greatly aided by the use of computational models of lung mechanical function that can be matched to physiological measurements made in a given patient. In this review, we discuss recent models that have the potential to serve as the basis for devising minimally injurious modes of mechanical ventilation in ARDS patients. PMID- 26904139 TI - In silico models of M. tuberculosis infection provide a route to new therapies. AB - Tuberculosis (TB) is a global health problem responsible for ~2 million deaths per year. Current antibiotic treatments are lengthy and fraught with compliance and resistance issues. There is a crucial need for additional approaches to provide a cost-effective means of exploring the design space for potential therapies. We discuss the use of mathematical and computational models in virtual experiments and virtual clinical trials both to develop new hypotheses regarding the disease and to provide a cost-effective means of discovering new treatment strategies. PMID- 26904141 TI - The Score Model Containing Chinese Medicine Syndrome Element of Blood Stasis Presented a Better Performance Compared to APRI and FIB-4 in Diagnosing Advanced Fibrosis in Patients with Chronic Hepatitis B. AB - This study aims to explore a useful noninvasive assessment containing TCM syndrome elements for liver fibrosis in CHB patients. The demographic, clinical, and pathological data were retrospectively collected from 709 CHB patients who had ALT less than 2 times the upper limit of normal from April 2009 to October 2012. Logistical regression and area under receiver-operator curve (AUROC) were used to determine the diagnostic performances of simple tests for advanced fibrosis (Scheuer stage, F >= 3). Results showed that the most common TCM syndrome element observed in this CHB population was dampness and Qi stagnation, followed by blood stasis, by heat, and less by Qi deficiency and Yin deficiency. The logistical regression analysis identified AST >= 35 IU/L, PLT <= 161 * 10(9)/L, and TCM syndrome element of blood stasis as the independent risk factors for advanced fibrosis. Therefore, a score model containing these three factors was established and tested. The score model containing blood stasis resulted in a higher AUC (AUC = 0.936) compared with APRI (AUC = 0.731) and FIB-4 (AUC = 0.709). The study suggested that the score model containing TCM syndrome element of blood stasis could be used as a useful diagnostic tool for advanced fibrosis in CHB patients and presented a better performance compared to APRI and FIB-4. PMID- 26904140 TI - Effects of Common Fig (Ficus carica) Leaf Extracts on Sperm Parameters and Testis of Mice Intoxicated with Formaldehyde. AB - Formaldehyde (FA) is the leading cause of cellular injury and oxidative damage in testis that is one of the main infertility causes. There has been an increasing evidence of herbal remedies use in male infertility treatment. This assay examines the role of Ficus carica (Fc) leaf extracts in sperm parameters and testis of mice intoxicated with FA. Twenty-five adult male mice were randomly divided into control; sham; FA-treated (10 mg/kg twice per day); Fc-treated (200 mg/kg); and FA + Fc-treated groups. Cauda epididymal spermatozoa were analyzed for viability, count, and motility. Testes were weighed and gonadosomatic index (GSI) was calculated. Also, histoarchitecture of seminiferous tubules was assessed in the Haematoxylin and Eosin stained paraffin sections. The findings showed that FA significantly decreased GSI and increased percentage of immotile sperm compared with control group. Disorganized and vacuolated seminiferous epithelium, spermatogenic arrest, and lumen filled with immature germ cells were also observed in the testes. However, Fc leaf extracts improved sperm count, nonprogressive motility of spermatozoa, and GSI in FA-treated testes. Moreover, seminiferous tubule with spermatogenic arrest was rarely seen, indicating that Fc has the positive effects on testis and epididymal sperm parameters exposed with FA. PMID- 26904142 TI - Antiobesity Effects of Unripe Rubus coreanus Miquel and Its Constituents: An In Vitro and In Vivo Characterization of the Underlying Mechanism. AB - Background. The objective of the present study was to perform a bioguided fractionation of unripe Rubus coreanus Miquel (uRC) and evaluate the lipid accumulation system involvement in its antiobesity activity as well as study the uRC mechanism of action. Results. After the fractionation, the BuOH fraction of uRC (uRCB) was the most active fraction, suppressing the differentiation of 3T3 L1 adipocytes in a dose-dependent manner. Moreover, after an oral administration for 8 weeks in HFD-induced obese mice, uRCB (10 and 50 mg/kg/day) produced a significant decrease in body weight, food efficiency ratio, adipose tissue weight and LDL-cholesterol, serum glucose, TC, and TG levels. Similarly, uRCB significantly suppressed the elevated mRNA levels of PPARgamma in the adipose tissue in vivo. Next, we investigated the antiobesity effects of ellagic acid, erycibelline, 5-hydroxy-2-pyridinemethanol, m-hydroxyphenylglycine, and 4 hydroxycoumarin isolated from uRCB. Without affecting cell viability, five bioactive compounds decreased the lipid accumulation in the 3T3-L1 cells and the mRNA expression levels of key adipogenic genes such as PPARgamma, C/EBPalpha, SREBP-1c, ACC, and FAS. Conclusion. These results suggest that uRC and its five bioactive compounds may be a useful therapeutic agent for body weight control by downregulating adipogenesis and lipogenesis. PMID- 26904143 TI - Estimation of Bioactive Compound, Maslinic Acid by HPTLC, and Evaluation of Hepatoprotective Activity on Fruit Pulp of Ziziphus jujuba Mill. Cultivars in India. AB - Fruits of Ziziphus jujuba Mill. (family: Rhamnaceae), known as Indian jujube or "Ber," are of potential nutritional and medicinal value. The objectives of the present study were to estimate bioactive compound maslinic acid by HPTLC method and to evaluate in vitro antioxidant and hepatoprotective activity of eight cultivars of Indian jujube. Maslinic acid and the fruit pulp of various cultivars of Indian jujube, namely, Gola, Sannur, Umaran, Mehrun, and Chhuhara, exhibited significantly high antioxidant and hepatoprotective activity. HPTLC-densitometric method was developed for quantification of maslinic acid from fruits of Indian jujube cultivars. The trend of occurrence of maslinic acid in fruits pulp extracts was as follows: Gola > Sannur > Umaran > Mehrun > Chhuhara > Wild > Kadaka > Apple. A significant correlation was shown by maslinic acid content and prevention of oxidative stress induced by CCl4 in liver slice culture cell treated with extract. Maslinic acid along with its other phytoconstituents like phenols, flavonoids, and ascorbic acid may act as a possible therapeutic agent for preventing hepatotoxicity caused by oxidative stress generated due to the prooxidants like CCl4. This is the first report of fruit pulp extracts of Z. jujube cultivars in India and maslinic acid preventing CCl4 induced damage in liver slice culture cell of mice. PMID- 26904145 TI - Corrigendum to "Effects of a Mindfulness Meditation Course on Learning and Cognitive Performance among University Students in Taiwan". AB - [This corrects the article DOI: 10.1155/2015/254358.]. PMID- 26904144 TI - Principle Study of Head Meridian Acupoint Massage to Stress Release via Grey Data Model Analysis. AB - This paper presents the scientific study of the effectiveness and action principle of head meridian acupoint massage by applying the grey data model analysis approach. First, the head massage procedure for massaging the important head meridian acupuncture points including Taiyang, Fengfu, Tianzhu, Fengqi, and Jianjing is formulated in a standard manner. Second, the status of the autonomic nervous system of each subject is evaluated by using the heart rate variability analyzer before and after the head massage following four weeks. Afterward, the physiological factors of autonomic nerves are quantitatively analyzed by using the grey data modeling theory. The grey data analysis can point out that the status of autonomic nervous system is greatly improved after the massage. The order change of the grey relationship weighting of physiological factors shows the action principle of the sympathetic and parasympathetic nerves when performing head massage. In other words, the grey data model is able to distinguish the detailed interaction of the autonomic nervous system and the head meridian acupoint massage. Thus, the stress relaxing effect of massaging head meridian acupoints is proved, which is lacked in literature. The results can be a reference principle for massage health care in practice. PMID- 26904146 TI - Antibacterial Activity of Salvadora persica L. (Miswak) Extracts against Multidrug Resistant Bacterial Clinical Isolates. AB - Much effort has focused on examining the inhibitory effect of Salvadora persica (miswak) on oral microorganisms, but information concerning its antibacterial activity against other human pathogens, particularly multidrug resistant (MDR) isolates, is scarce. Therefore, this study aimed to assess the in vitro antibacterial activities of Salvadora persica L. extracts against 10 MDR bacterial clinical isolates other than oral pathogens. The antibacterial activity of aqueous and methanol miswak extracts was assessed using the agar dilution and minimum inhibitory concentration (MIC) methods. Overall, the 400 mg/mL of miswak extract was the most effective on all strains. The methanol extract exhibited a stronger antibacterial activity against Gram-negative (3.3-13.6 mm) than Gram positive (1.8-8.3 mm) bacteria. The lowest MIC value was seen for E. coli (0.39, 1.56 ug/mL), followed by Streptococcus pyogenes (1.56 ug/mL). The highest MIC value (6.25, 12.5 ug/mL) was recorded for methicillin-resistant Staphylococcus aureus (MRSA), Acinetobacter baumannii, and Stenotrophomonas maltophilia. This study demonstrates, for the first time, the moderate to strong antibacterial activity of miswak extracts against all tested MDR-pathogens. Methanol extract appears to be a potent antimicrobial agent that could be considered as complementary and alternative medicine against resistant pathogens. Further studies on a large number of MDR organisms are necessary to investigate and standardize the inhibitory effect of miswak extracts against these emerging pathogens. PMID- 26904147 TI - Electroacupuncture Reduces Weight Gain Induced by Rosiglitazone through PPARgamma and Leptin Receptor in CNS. AB - We investigate the effect of electroacupuncture (EA) on protecting the weight gain side effect of rosiglitazone (RSG) in type 2 diabetes mellitus (T2DM) rats and its possible mechanism in central nervous system (CNS). Our study showed that RSG (5 mg/kg) significantly increased the body weight and food intake of the T2DM rats. After six-week treatment with RSG combined with EA, body weight, food intake, and the ratio of IWAT to body weight decreased significantly, whereas the ratio of BAT to body weight increased markedly. HE staining indicated that the T2DM-RSG rats had increased size of adipocytes in their IWAT, but EA treatment reduced the size of adipocytes. EA effectively reduced the lipid contents without affecting the antidiabetic effect of RSG. Furthermore, we noticed that the expression of PPARgamma gene in hypothalamus was reduced by EA, while the expressions of leptin receptor and signal transducer and activator of transcription 3 (STAT3) were increased. Our results suggest that EA is an effective approach for inhibiting weight gain in T2DM rats treated by RSG. The possible mechanism might be through increased levels of leptin receptor and STAT3 and decreased PPARgamma expression, by which food intake of the rats was reduced and RSG-induced weight gain was inhibited. PMID- 26904149 TI - The Protective Effects of Isoliquiritigenin and Glycyrrhetinic Acid against Triptolide-Induced Oxidative Stress in HepG2 Cells Involve Nrf2 Activation. AB - Triptolide (TP), an active ingredient of Tripterygium wilfordii Hook f., possesses a wide range of biological activities. Oxidative stress likely plays a role in TP-induced hepatotoxicity. Isoliquiritigenin (ISL) and glycyrrhetinic acid (GA) are potent hepatoprotection agents. The aim of the present study was to investigate whether Nrf2 pathway is associated with the protective effects of ISL and GA against TP-induced oxidative stress or not. HepG2 cells were treated with TP (50 nM) for 24 h after pretreatment with ISL and GA (5, 10, and 20 MUM) for 12 h and 24 h, respectively. The results demonstrated that TP treatment significantly increased ROS levels and decreased GSH levels. Both ISL and GA pretreatment decreased ROS and meanwhile enhanced intracellular GSH content. Additionally, TP treatment obviously decreased the protein expression of Nrf2 and its target genes including HO-1 and MRP2 except NQO1. Moreover, both ISL and GA displayed activities as inducers of Nrf2 and increased the expression of HO-1, NQO1, and MRP2. Taken together the current data confirmed that ISL and GA could activate the Nrf2 antioxidant response in HepG2 cells, increasing the expression of its target genes which may be partly associated with their protective effects in TP-induced oxidative stress. PMID- 26904148 TI - Glycyrrhizic Acid Attenuates Sepsis-Induced Acute Kidney Injury by Inhibiting NF kappaB Signaling Pathway. AB - Glycyrrhizic acid (GA) is a major active ingredient in licorice. In our study, the effects of GA on acute kidney injury (AKI) in rats and its underlying molecular mechanisms were investigated. The sepsis model was produced by caecal ligation and puncture (CLP) in rats. The molecular and histological experiments were performed in the kidney tissues and serum samples of rats. According to the results obtained, GA alleviated sepsis-induced AKI by improving the pathological changes, decreasing the levels of blood urea nitrogen (BUN), creatinine (Cre), and increasing the survival rate of rats with AKI significantly. The production of inflammatory cytokines, such as TNF-alpha, IL-1beta, and IL-6, was markedly inhibited by GA. Moreover, treatment with GA inhibited the production of nitric oxide (NO) and prostaglandin E2 (PGE2) and expression levels of induced nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in kidney tissues. Furtherly, the apoptosis in kidney tissue induced by AKI was suppressed by GA. Finally, GA could inhibit the activation of NF-kappaB signaling pathway. Our study suggests that GA alleviates sepsis-induced AKI by inhibiting the NF-kappaB signaling pathway, which provides a strong evidence for a new approach for treating sepsis induced AKI. PMID- 26904150 TI - Population Dynamics of Patients with Bacterial Resistance in Hospital Environment. AB - During the past decades, the increase of antibiotic resistance has become a major concern worldwide. The researchers found that superbugs with new type of resistance genes (NDM-1) have two aspects of transmission characteristics; the first is that the antibiotic resistance genes can horizontally transfer among bacteria, and the other is that the superbugs can spread between humans through direct contact. Based on these two transmission mechanisms, we study the dynamics of population in hospital environment where superbugs exist. In this paper, we build three mathematic models to illustrate the dynamics of patients with bacterial resistance in hospital environment. The models are analyzed using stability theory of differential equations. Positive equilibrium points of the system are investigated and their stability analysis is carried out. Moreover, the numerical simulation of the proposed model is also performed which supports the theoretical findings. PMID- 26904151 TI - Geodesic Distance Algorithm for Extracting the Ascending Aorta from 3D CT Images. AB - This paper presents a method for the automatic 3D segmentation of the ascending aorta from coronary computed tomography angiography (CCTA). The segmentation is performed in three steps. First, the initial seed points are selected by minimizing a newly proposed energy function across the Hough circles. Second, the ascending aorta is segmented by geodesic distance transformation. Third, the seed points are effectively transferred through the next axial slice by a novel transfer function. Experiments are performed using a database composed of 10 patients' CCTA images. For the experiment, the ground truths are annotated manually on the axial image slices by a medical expert. A comparative evaluation with state-of-the-art commercial aorta segmentation algorithms shows that our approach is computationally more efficient and accurate under the DSC (Dice Similarity Coefficient) measurements. PMID- 26904152 TI - Forward Stagewise Shrinkage and Addition for High Dimensional Censored Regression. AB - Despite enormous development on variable selection approaches in recent years, modeling and selection of high dimensional censored regression remains a challenging question. When the number of predictors p far exceeds the number of observational units n and the outcome is censored, computations of existing solutions often become difficult, or even infeasible in some situations, while performances frequently deteriorate. In this article, we aim at simultaneous model estimation and variable selection for Cox proportional hazards models with high dimensional covariates. We propose a forward stage-wise shrinkage and addition approach for that purpose. Our proposal extends a popular statistical learning technique, the boosting method. It inherits the flexible nature of boosting and is straightforward to extend to nonlinear Cox models. Meanwhile it advances the classical boosting method by adding explicit variable selection and substantially reducing the number of iterations to the algorithm convergence. Our intensive simulations have showed that the new method enjoys a competitive performance in Cox models with both p < n and p >= n scenarios. The new method was also illustrated with analysis of two real microarray survival datasets. PMID- 26904154 TI - Standardized Scalp Massage Results in Increased Hair Thickness by Inducing Stretching Forces to Dermal Papilla Cells in the Subcutaneous Tissue. AB - OBJECTIVE: In this study, we evaluated the effect of scalp massage on hair in Japanese males and the effect of stretching forces on human dermal papilla cells in vitro. METHODS: Nine healthy men received 4 minutes of standardized scalp massage per day for 24 weeks using a scalp massage device. Total hair number, hair thickness, and hair growth rate were evaluated. The mechanical effect of scalp massage on subcutaneous tissue was analyzed using a finite element method. To evaluate the effect of mechanical forces, human dermal papilla cells were cultured using a 72-hour stretching cycle. Gene expression change was analyzed using DNA microarray analyses. In addition, expression of hair cycle-related genes including IL6, NOGGIN, BMP4, and SMAD4 were evaluated using real-time reverse transcription-polymerase chain reaction. RESULTS: Standardized scalp massage resulted in increased hair thickness 24 weeks after initiation of massage (0.085 +/- 0.003 mm vs 0.092 +/- 0.001 mm). Finite element method showed that scalp massage caused z-direction displacement and von Mises stress on subcutaneous tissue. In vitro, DNA microarray showed gene expression change significantly compared with nonstretching human dermal papilla cells. A total of 2655 genes were upregulated and 2823 genes were downregulated. Real-time reverse transcription-polymerase chain reaction demonstrated increased expression of hair cycle-related genes such as NOGGIN, BMP4, SMAD4, and IL6ST and decrease in hair loss-related genes such as IL6. CONCLUSIONS: Stretching forces result in changes in gene expression in human dermal papilla cells. Standardized scalp massage is a way to transmit mechanical stress to human dermal papilla cells in subcutaneous tissue. Hair thickness was shown to increase with standardized scalp massage. PMID- 26904155 TI - Congenital Melanocytic Nevi. PMID- 26904153 TI - Biobanks in the era of personalized medicine: objectives, challenges, and innovation: Overview. AB - Biobanks are an important compound of personalized medicine and strongly support the scientific progress in stratification of population and biomarker discovery and validation due to progress in personalized medicine. Biobanks are an essential tool for new drug discoveries and drug development. Biobanks play an important role in the whole process of patient prevention and prediction, follow up, and therapy monitoring and optimalization. Biobanks have the specificity in that they cover multidisciplinary approach to the human health combining biological and medical approaches, as well as informative bioinformatics technologies, computationing, and modeling. The importance of biobanks has during the last decade increased in variety and capacity from small collections of samples to large-scale national or international repositories. Collected samples are population-based, disease-specific or rare diseases originating from a diverse profile of individuals. There are various purposes of biobanks, such as diagnostics, pharmacology, or research. Biobanks involve, store, and operate with specific personal information, and as a consequence, such a diversity of biobanking is associated with a broad spectrum of ethical and legal issues. Biobanks are an international phenomenon because any single country, state, or society at the moment is not able to cover all issues involving the whole biobank problematic. Biobanks have an enormous innovative potential in the whole process of biomedical research in the twenty-first century. PMID- 26904156 TI - A lurking threat: transfer of peanut allergy through peripheral blood stem cell transplantation. AB - BACKGROUND: There exist several reports of atopy and allergen-specific IgE mediated hypersensitivity transferred by bone marrow transplantation, and it has been concluded that the transfer of allergic reactivity results from adoptive transfer of IgE-producing donor-derived B- and/or plasma cells. To the best of our knowledge we report the first case of peanut allergy after PBSCT. CASE PRESENTATION: A 55-year-old anciently non allergic man with secondary acute myeloid leukemia (AML) received an allogeneic peripheral blood stem cell transplantation from a matched unrelated donor following reduced-intensity conditioning. On day 32 after PBSCT, while still on prophylactic systemic immunosuppression, the patient noticed a first episode of angioedema with swelling of the nasal and oral mucosa 30 min after consuming peanut puffs. In a second episode, eight months after PBSCT, he again developed angioedema, generalized pruritus and nausea within minutes after eating biscuits containing hazelnut and peanut. Moreover, after topical application of a peanut oil containing ointment, the patient experienced facial erythema and angioedema. Nine months after PBSCT an evaluation for peanut allergy revealed a highly increased specific IgE to peanut of 75.9 kU/l. Accordingly, skin prick tests for peanut extract were also positive. In consequence, the patient was counseled to strictly avoid peanut-related products, and provided with an emergency set. No adverse allergic events have occurred since for an observation time of 15 months after PBSCT. The stem cell donor was contacted and confirmed intolerance to peanuts. His specific serum IgE pattern nine month after PBSCT harvest was analysed and showed similar sensitization profiles compared to those of the transplant recipient. CONCLUSIONS: Because of the close temporal association between the onset of allergic symptoms in the PBSC recipient it is reasonable to assume that the acquired peanut allergy had been transferred from the donor to the recipient by the PBSC graft. PMID- 26904157 TI - CD4(+)CD25(high)CD127(-) regulatory T-cells in COPD: smoke and drugs effect. AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a progressive lung disorder characterized by poorly reversible airway obstruction and its pathogenesis remains largely misunderstood. Local changes of regulatory T-cell populations in the lungs of COPD patients have been demonstrated although data concerning their pathologic role are contrasting. The aim of our study was to evaluate the relative percentage of regulatory T-cells in the peripheral blood of current and former smoker subjects, affected or not by COPD. Furthermore, the effect of different concentrations of budesonide and formoterol, on regulatory T cells has been investigated. METHODS: T regulatory lymphocytes were isolated and assessed as CD4(+)CD25(high)CD127(-) cells by flow cytometry and cultured for 48 hours in the absence or in the presence of budesonide and/or formoterol at different doses. RESULTS: CD4(+)CD25(high)CD127(-) regulatory T-cells percentage was significantly reduced in COPD patients, both current and former smokers, with respect to volunteers. Furthermore, CD4(+)CD25(high)CD127(-) cells of COPD patients showed a not statistically significant response to drugs compared to healthy subjects. DISCUSSION: Our results evidenced a different behaviour of CD4(+)CD25(high)CD127(-) Treg cells in COPD patients after in vitro treatments. CONCLUSIONS: Based on our data, we suggested a possible role of CD4 CD25(high)CD127 T-cells in COPD pathogenesis. PMID- 26904159 TI - Biomarkers of the involvement of mast cells, basophils and eosinophils in asthma and allergic diseases. AB - Biomarkers of disease activity have come into wide use in the study of mechanisms of human disease and in clinical medicine to both diagnose and predict disease course; as well as to monitor response to therapeutic intervention. Here we review biomarkers of the involvement of mast cells, basophils, and eosinophils in human allergic inflammation. Included are surface markers of cell activation as well as specific products of these inflammatory cells that implicate specific cell types in the inflammatory process and are of possible value in clinical research as well as within decisions made in the practice of allergy-immunology. PMID- 26904160 TI - Use of Carnosine for Oxidative Stress Reduction in Different Pathologies. AB - The main properties and biological effects of the antioxidant carnosine, the natural dipeptide beta-alanyl-L-histidine, are considered. Data on the effective use of carnosine in different pathologies are presented. Special attention is paid to issues of use of carnosine in neurologic and mental diseases, in alcoholism as well as in physiological states accompanied by activation of free radical processes and formation of oxidative stress. PMID- 26904161 TI - Mechanisms of Neuroprotection by Quercetin: Counteracting Oxidative Stress and More. AB - Increasing interest has recently focused on determining whether several natural compounds, collectively referred to as nutraceuticals, may exert neuroprotective actions in the developing, adult, and aging nervous system. Quercetin, a polyphenol widely present in nature, has received the most attention in this regard. Several studies in vitro, in experimental animals and in humans, have provided supportive evidence for neuroprotective effects of quercetin, either against neurotoxic chemicals or in various models of neuronal injury and neurodegenerative diseases. The exact mechanisms of such protective effects remain elusive, though many hypotheses have been formulated. In addition to a possible direct antioxidant effect, quercetin may also act by stimulating cellular defenses against oxidative stress. Two such pathways include the induction of Nrf2-ARE and induction of the antioxidant/anti-inflammatory enzyme paraoxonase 2 (PON2). In addition, quercetin has been shown to activate sirtuins (SIRT1), to induce autophagy, and to act as a phytoestrogen, all mechanisms by which quercetin may provide its neuroprotection. PMID- 26904162 TI - Antioxidant and Antifatigue Properties of the Aqueous Extract of Moringa oleifera in Rats Subjected to Forced Swimming Endurance Test. AB - The effects of the aqueous extract of Moringa oleifera on swimming performance and related biochemical parameters were investigated in male Wistar rats (130-132 g). Four groups of rats (16 per group) were fed a standard laboratory diet and given distilled water, 100, 200, or 400 mg/kg of extract, respectively, for 28 days. On day 28, 8 rats from each group were subjected to the forced swimming test with tail load (10% of body weight). The remaining 8 rats per group were subjected to the 90-minute free swim. Maximum swimming time, glycemia, lactamia, uremia, triglyceridemia, hepatic and muscle glycogen, hematological parameters, and oxidative stress parameters (superoxide dismutase, catalase, reduced glutathione, and malondialdehyde) were measured. Results. M. oleifera extract increased maximum swimming time, blood hemoglobin, blood glucose, and hepatic and muscle glycogen reserves. The extract also increased the activity of antioxidant enzymes and decreased the blood concentrations of malondialdehyde. Furthermore, it decreased blood concentrations of lactate, triglycerides, and urea. In conclusion, the antifatigue properties of M. oleifera extract are demonstrated by its ability to improve body energy stores and tissue antioxidant capacity and to reduce the tissue build-up of lactic acid. PMID- 26904165 TI - Epithelial Electrolyte Transport Physiology and the Gasotransmitter Hydrogen Sulfide. AB - Hydrogen sulfide (H2S) is a well-known environmental chemical threat with an unpleasant smell of rotten eggs. Aside from the established toxic effects of high dose H2S, research over the past decade revealed that cells endogenously produce small amounts of H2S with physiological functions. H2S has therefore been classified as a "gasotransmitter." A major challenge for cells and tissues is the maintenance of low physiological concentrations of H2S in order to prevent potential toxicity. Epithelia of the respiratory and gastrointestinal tract are especially faced with this problem, since these barriers are predominantly exposed to exogenous H2S from environmental sources or sulfur-metabolising microbiota. In this paper, we review the cellular mechanisms by which epithelial cells maintain physiological, endogenous H2S concentrations. Furthermore, we suggest a concept by which epithelia use their electrolyte and liquid transport machinery as defence mechanisms in order to eliminate exogenous sources for potentially harmful H2S concentrations. PMID- 26904166 TI - Decavanadate Toxicology and Pharmacological Activities: V10 or V1, Both or None? AB - This review covers recent advances in the understanding of decavanadate toxicology and pharmacological applications. Toxicological in vivo studies point out that V10 induces several changes in several oxidative stress parameters, different from the ones observed for vanadate (V1). In in vitro studies with mitochondria, a particularly potent V10 effect, in comparison with V1, was observed in the mitochondrial depolarization (IC50 = 40 nM) and oxygen consumption (99 nM). It is suggested that mitochondrial membrane depolarization is a key event in decavanadate induction of necrotic cardiomyocytes death. Furthermore, only decavanadate species and not V1 potently inhibited myosin ATPase activity stimulated by actin (IC50 = 0.75 MUM) whereas exhibiting lower inhibition activities for Ca(2+)-ATPase activity (15 MUM) and actin polymerization (17 MUM). Because both calcium pump and actin decavanadate interactions lead to its stabilization, it is likely that V10 interacts at specific locations with these proteins that protect against hydrolysis but, on the other hand, it may induce V10 reduction to oxidovanadium(IV). Putting it all together, it is suggested that the pharmacological applications of V10 species and compounds whose mechanism of action is still to be clarified might involve besides V10 and V1 also vanadium(IV) species. PMID- 26904163 TI - Aerobic Exercise and Pharmacological Therapies for Skeletal Myopathy in Heart Failure: Similarities and Differences. AB - Skeletal myopathy has been identified as a major comorbidity of heart failure (HF) affecting up to 20% of ambulatory patients leading to shortness of breath, early fatigue, and exercise intolerance. Neurohumoral blockade, through the inhibition of renin angiotensin aldosterone system (RAS) and beta-adrenergic receptor blockade (beta-blockers), is a mandatory pharmacological therapy of HF since it reduces symptoms, mortality, and sudden death. However, the effect of these drugs on skeletal myopathy needs to be clarified, since exercise intolerance remains in HF patients optimized with beta-blockers and inhibitors of RAS. Aerobic exercise training (AET) is efficient in counteracting skeletal myopathy and in improving functional capacity and quality of life. Indeed, AET has beneficial effects on failing heart itself despite being of less magnitude compared with neurohumoral blockade. In this way, AET should be implemented in the care standards, together with pharmacological therapies. Since both neurohumoral inhibition and AET have a direct and/or indirect impact on skeletal muscle, this review aims to provide an overview of the isolated effects of these therapeutic approaches in counteracting skeletal myopathy in HF. The similarities and dissimilarities of neurohumoral inhibition and AET therapies are also discussed to identify potential advantageous effects of these combined therapies for treating HF. PMID- 26904164 TI - Skin Antiageing and Systemic Redox Effects of Supplementation with Marine Collagen Peptides and Plant-Derived Antioxidants: A Single-Blind Case-Control Clinical Study. AB - Recently, development and research of nutraceuticals based on marine collagen peptides (MCPs) have been growing due to their high homology with human collagens, safety, bioavailability through gut, and numerous bioactivities. The major concern regarding safety of MCPs intake relates to increased risk of oxidative stress connected with collagen synthesis (likewise in fibrosis) and to ROS production by MCPs-stimulated phagocytes. In this clinical-laboratory study, fish skin MCPs combined with plant-derived skin-targeting antioxidants (AO) (coenzyme Q10 + grape-skin extract + luteolin + selenium) were administered to volunteers (n = 41). Skin properties (moisture, elasticity, sebum production, and biological age) and ultrasonic markers (epidermal/dermal thickness and acoustic density) were measured thrice (2 months before treatment and before and after cessation of 2-month oral intake). The supplementation remarkably improved skin elasticity, sebum production, and dermal ultrasonic markers. Metabolic data showed significant increase of plasma hydroxyproline and ATP storage in erythrocytes. Redox parameters, GSH/coenzyme Q10 content, and GPx/GST activities were unchanged, while NO and MDA were moderately increased within, however, normal range of values. Conclusions. A combination of MCPs with skin-targeting AOs could be effective and safe supplement to improve skin properties without risk of oxidative damage. PMID- 26904167 TI - TGF-beta and Hypoxia/Reoxygenation Promote Radioresistance of A549 Lung Cancer Cells through Activation of Nrf2 and EGFR. AB - Although many studies have examined the roles of hypoxia and transforming growth factor- (TGF-) beta separately in the tumor microenvironment, the effects of simultaneous treatment with hypoxia/reoxygenation and TGF-beta on tumor malignancy are unclear. Here, we investigated the effects of redox signaling and oncogenes on cell proliferation and radioresistance in A549 human lung cancer cells in the presence of TGF-beta under hypoxia/reoxygenation conditions. Combined treatment with TGF-beta and hypoxia activated epidermal growth factor receptor (EGFR) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2), a redox sensitive transcription factor. Interestingly, Nrf2 knockdown suppressed the effects of combined treatment on EGFR phosphorylation. In addition, blockade of EGFR signaling also suppressed induction of Nrf2 following combined treatment with hypoxia and TGF-beta, indicating that the combined treatment induced positive crosstalk between Nrf2 and EGFR. TGF-beta and hypoxia/reoxygenation increased the accumulation of reactive oxygen species (ROS), while treatment with N-acetyl-l-cysteine abolished the activation of Nrf2 and EGFR. Treatment with TGF beta under hypoxic conditions increased the proliferation of A549 cells compared with that after vehicle treatment. Moreover, cells treated with the combined treatment exhibited resistance to ionizing radiation (IR), and knockdown of Nrf2 increased IR-induced cell death under these conditions. Thus, taken together, our findings suggested that TGF-beta and hypoxia/reoxygenation promoted tumor progression and radioresistance of A549 cells through ROS-mediated activation of Nrf2 and EGFR. PMID- 26904168 TI - Beneficial Effects of Physical Exercise on Functional Capacity and Skeletal Muscle Oxidative Stress in Rats with Aortic Stenosis-Induced Heart Failure. AB - Objective. We evaluated the influence of exercise on functional capacity, cardiac remodeling, and skeletal muscle oxidative stress, MAPK, and NF-kappaB pathway in rats with aortic stenosis- (AS-) induced heart failure (HF). Methods and Results. Eighteen weeks after AS induction, rats were assigned into sedentary control (C Sed), exercised control (C-Ex), sedentary AS (AS-Sed), and exercised AS (AS-Ex) groups. Exercise was performed on treadmill for eight weeks. Statistical analyses were performed with Goodman and ANOVA or Mann-Whitney. HF features frequency and mortality did not differ between AS groups. Exercise improved functional capacity, assessed by maximal exercise test on treadmill, without changing echocardiographic parameters. Soleus cross-sectional areas did not differ between groups. Lipid hydroperoxide concentration was higher in AS-Sed than C-Sed and AS Ex. Activity of antioxidant enzymes superoxide dismutase and glutathione peroxidase was changed in AS-Sed and restored in AS-Ex. NADPH oxidase activity and gene expression of its subunits did not differ between AS groups. Total ROS generation was lower in AS-Ex than C-Ex. Exercise modulated MAPK in AS-Ex and did not change NF-kappaB pathway proteins. Conclusion. Exercise improves functional capacity in rats with AS-induced HF regardless of echocardiographic parameter changes. In soleus, exercise reduces oxidative stress, preserves antioxidant enzyme activity, and modulates MAPK expression. PMID- 26904170 TI - Editorial: Utilization of Hybrid PET/MR in Neuroimaging. PMID- 26904169 TI - Bioactive Flavonoids, Antioxidant Behaviour, and Cytoprotective Effects of Dried Grapefruit Peels (Citrus paradisi Macf.). AB - Grapefruit (Citrus paradisi Macf.) is an important cultivar of the Citrus genus which contains a number of nutrients beneficial to human health. The objective of the present study was to evaluate changes in bioactive flavonoids, antioxidant behaviour, and in vitro cytoprotective effect of processed white and pink peels after oven-drying (45 degrees C-60 degrees C) and freeze-drying treatments. Comparison with fresh grapefruit peels was also assessed. Significant increases in DPPH, FRAPS, and ABTS values were observed in dried grapefruit peel samples in comparison with fresh peels, indicating the suitability of the treatments for use as tools to greatly enhance the antioxidant potential of these natural byproducts. A total of thirteen flavonoids were quantified in grapefruit peel extracts by HPLC-MS/MS. It was found that naringin, followed by isonaringin, was the main flavonoid occurring in fresh, oven-dried, and freeze-dried grapefruit peels. In vivo assay revealed that fresh and oven-dried grapefruit peel extracts (45 degrees C) exerted a strong cytoprotective effect on SH-SY5Y neuroblastoma cell lines at concentrations ranging within 0.1-0.25 mg/mL. Our data suggest that grapefruit (Citrus paradisi Macf.) peel has considerable potential as a source of natural bioactive flavonoids with outstanding antioxidant activity which can be used as agents in several therapeutic strategies. PMID- 26904171 TI - Study the Effect of Endocannabinoid System on Rat Behavior in Elevated Plus-Maze. AB - INTRODUCTION: Previous studies have shown that cannabinoidergic system is involved in anxiety. However, there are controversial reports in the experimental studies. The aim of this study is to evaluate the effect of pharmacological stimulation or blocking of CB1 receptors and inhibition of endocannabinoid degradation in anxiety like behavior in elevated plus-maze (EPM) test in rat. The EPM is one of the most widely used animal models of anxiety. METHODS: Male Wistar rats were randomly allocated to ten groups. Different groups of animals intraperitoneally received Win-55212 (0.3, 1 and 5 mg/kg) as CB1 receptor agonist, AM-251 (0.3, 1 and 5 mg/kg) as CB1 receptor antagonist, URB-597 (0.03, 0.1 and 0.3 mg/kg) as endocannabinoid breakdown inhibitor or saline (as control group) 30 min before submitting into EPM test. RESULTS: The results showed that compared to the control group, Win-55212 (1 and 5 mg/kg) and URB-597 (0.1 and 0.3 mg/kg) significantly increased both of the time and percentage of entries into open arms. AM-251 (1 and 5 mg/kg) significantly decreased the time and percentage of entries into open arms in the EPM test. These substances have no effects on the total distance covered by animals and number of closed arm entries. DISCUSSION: It is concluded that activation of cannabinoid receptor exert anxiolytic effect while blocking of cannabinoid receptor resulted in anxiety behavior. The locomotor activity was not significantly changed by cannabinoid system. It is suggested that potentiation of cannabinoid system may be therapeutic strategy for the anxiety behavior. PMID- 26904172 TI - Glucocorticoids Interact with Cholinergic System in Impairing Memory Reconsolidation of an Inhibitory Avoidance Task in Mice. AB - INTRODUCTION: Recent studies suggest that glucocorticoids modulate memory reconsolidation. Moreover, cholinergic system is involved in memory reconsolidation. Since glucocorticoids interact with brain cholinergic system in modulating memory processing, we investigated whether glucocorticoid influences on the reconsolidation of emotionally arousing training depend on the cholinergic system. METHODS: Mice were trained (1mA, 3s footshock) in an inhibitory avoidance task. Forty-eight hours after training, memory reactivation was occurred (Test 1), and different treatments were given. Two (Test 2), five (Test 3), and seven days (Test 4) after memory reactivation (Test 1), animals were retested for fear memory retention. RESULTS: In the first experiment, we observed that administration of corticosterone (CORT, 0.3, 1 and 3 mg/kg) following memory reactivation impaired subsequent expression of memory in a dose-dependent manner. In the second experiment, we found that CORT-induced impairment of memory reconsolidation was reversed by the muscarinic receptor antagonist atropine (0.5 and 2 mg/kg). In the third experiment, the nicotinic receptor antagonist mecaylamine (0.5 or 2 mg/kg) was not able to block the corticosterone response. DISCUSSION: These findings indicate that glucocorticoids impair memory reconsolidation by a muscarinic cholinergic mechanism. PMID- 26904173 TI - The Role of Hippocampal 5HT3 Receptors in Harmaline-Induced Memory Deficit. AB - INTRODUCTION: The plethora of studies indicated that there is a cross talk relationship between harmaline and serotonergic (5-HT) system on cognitive and non-cognitive behaviors. Thus, the purpose of this study is to assess the effects of hippocampal 5-HT4 receptor on memory acquisition deficit induced by harmaline. METHODS: Harmaline was injected peritoneally, while 5-HT4 receptor agonist (RS67333) and antagonist (RS23597-190) were injected intra-hippocampal. A single trial step-down passive avoidance, open field and tail flick tasks were used for measurement of memory, locomotor activity and pain responses, respectively. RESULTS: The data revealed that pre-training injection of higher dose of harmaline (1 mg/kg), RS67333 (0.5 ng/mouse) and RS23597-190 (0.5 ng/mouse) decreased memory acquisition process in the adult mice. Moreover, concurrent pre training administration of subthreshold dose of RS67333 (0.005 ng/mouse) or RS23597-190 (0.005 ng/mouse) with subthreshold dose of harmaline (0.5 mg/kg, i.p.) intensify impairment of memory acquisition. All above interventions did not change locomotion and tail flick behaviors. DISCUSSION: The results demonstrated that the synergistic effect between both hippocampal 5-HT4 receptor agonist and antagonist with impairment of memory acquisition induced by harmaline, indicating a modulatory effect for hippocampal 5HT4 receptor on Harmaline induced amnesia. PMID- 26904174 TI - Involvement of Mu Opioid Receptor Signaling in the Protective Effect of Opioid against 6-Hydroxydopamine-Induced SH-SY5Y Human Neuroblastoma Cells Apoptosis. AB - INTRODUCTION: The neuroprotective role of opioid morphine against 6 hydroxydopamine-induced cell death has been demonstrated. However, the exact mechanism(s) underlying such neuroprotection, especially the role of subtype receptors, has not yet been fully clarified. METHODS: Here, we investigated the effects of different opioid agonists on 6-OHDA-induced neurotoxicity in human neuroblastoma SH-SY5Y cell line as an in vitro model of Parkinson's disease. Cell damage was induced by 150 MUM 6-OHDA and the cells viability was examined by MTT assay. Intracellular calcium, reactive oxygen species and mitochondrial membrane potential were assessed by fluorescence spectrophotometry method. Immunoblot technique was used to evaluate cytochrome-c and activated caspase-3 as biochemical markers of apoptosis induction. RESULTS: The data showed that 6-OHDA caused significant cell damage, loss of mitochondrial membrane potential and increase in intracellular reactive oxygen species and calcium levels as well as activated caspase-3 and cytochrome-c release. Incubation of SH-SY5Y cells with MU opioid agonists, morphine and DAMGO, but not with delta-opioid agonist, DADLE, elicited protective effect and reduced biochemical markers of cell damage and death. DISCUSSION: The results suggest that MU-opioid receptors signaling participate in the opioid neuroprotective effects against 6-OHDA-induced neurotoxicity. PMID- 26904175 TI - X Chromosome Inactivation in Opioid Addicted Women. AB - INTRODUCTION: X chromosome inactivation (XCI) is a process during which one of the two X chromosomes in female human is silenced leading to equal gene expression with males who have only one X chromosome. Here we have investigated XCI ratio in females with opioid addiction to see whether XCI skewness in women could be a risk factor for opioid addiction. METHODS: 30 adult females meeting DSM IV criteria for opioid addiction and 30 control females with no known history of addiction were included in the study. Digested and undigested DNA samples which were extracted from blood were analyzed after amplification of the polymorphic androgen receptor (AR) gene located on the X chromosome. XCI skewness was studied in 3 ranges: 50:50-64:36 (random inactivation), 65:35-80:20 (moderately skewed) and >80:20 (highly skewed). RESULTS: XCI from informative females in control group was 63% (N=19) random, 27% (N=8) moderately skewed and 10% (N=3) highly skewed. Addicted women showed 57%, 23% and 20%, respectively. The distribution and frequency of XCI status in women with opioid addiction was not significantly different from control group (P=0.55). DISCUSSION: Our data did not approve our hypothesis of increased XCI skewness among women with opioid addiction or unbalanced (non-random) expression of genes associated with X chromosome in female opioid addicted subjects. PMID- 26904176 TI - Vitex Agnus Castus Extract Improves Learning and Memory and Increases the Transcription of Estrogen Receptor alpha in Hippocampus of Ovariectomized Rats. AB - INTRODUCTION: Lower level of estrogen hormone is considered as an important factor for loss of learning and memory in postmenopausal women. Although estrogen replacement therapy is used for compensation, but long-term usage of estrogen is associated with a higher risk of hormone-dependent cancers. Phytoestrogens, due to fewer side effects, have been proposed to prevent menopause-related cognitive decline. METHODS: 24 female Wistar rats weighing 180-220 g were used in this study. The animals were ovariectomized and randomly divided into four groups including, control and two groups which received 8 and 80 mg/kg Vitex agnus castus (VAC) ethanolic extract orally. The last groups were treated with 40 MUg/kg of estradiol valerat. Step-through passive avoidance (STPA) test was used for the evaluation of learning and memory. The hippocampal estrogen receptor alpha (ERalpha) expression was measured using Real-Time PCR. RESULTS: The results demonstrated that VAC extract or estradiol had better performance on step-through passive avoidance test than control group (all P<0.05). Moreover, administration of either estradiol or VAC extract increased the hippocampal mRNA level of ERalpha and prevented the decrease in uterine weight of ovariectomized rats. DISCUSSION: Based on our data, VAC extract improves learning and memory in ovariectomized rats. The positive effect of VAC extract on learning and memory is possibly associated with an increase in ERalpha gene expression in the hippocampal formation. PMID- 26904177 TI - The Effects of Fifa 2015 Computer Games on Changes in Cognitive, Hormonal and Brain Waves Functions of Young Men Volunteers. AB - INTRODUCTION: Computer games have attracted remarkable attentions in general publics with different cultures and their effects are subject of research by cognitive neuroscientists. In the present study, possible effects of the game Fifa 2015 on cognitive performance, hormonal levels, and electroencephalographic (EEG) signals were evaluated in young male volunteers. METHODS: Thirty two subjects aged 20 years on average participated mutually in playing computer game Fifa 2015. Identification information and general knowledge about the game were collected. Saliva samples from the contestants were obtained before and after the competition. Perceptive and cognitive performance including the general cognitive health, response delay, attention maintenance, and mental fatigue were measured using PASAT test. EEG were recorded during the play using EEG device and analyzed later using QEEG. Simultaneously, the players' behavior were recorded using a video camera. Saliva cortisol levels were assessed by ELISA kit. Data were analyzed by SPSS program. RESULTS: The impact of playing computer games on cortisol concentration of saliva before and after the game showed that the amount of saliva plasma after playing the game has dropped significantly. Also the impact of playing computer games on mental health, before and after the game indicated that the number of correct answers has not changed significantly. This indicates that sustained attention has increased in participants after the game in comparison with before that. Also it is shown that mental fatigue measured by PASAT test, did not changed significantly after the game in comparison to before that. The impact of game on changes in brain waves showed that the subjects in high activity state during playing the game had higher power of the EEG signals in most of the channels in lower frequency bands in compared to normal state. DISCUSSION: The present study showed that computer games can positively affect the stress system and the perceptual-cognitive system. Even though this impact was not significant in most cases, the changes in cognitive and hormonal test and also in brain waves were visible. Hence, due to the importance of this matter, it is necessary to create control systems in selecting the types of games for playing. PMID- 26904179 TI - Comparison of Swedish and Norwegian Use of Cone-Beam Computed Tomography: a Questionnaire Study. AB - OBJECTIVES: Cone-beam computed tomography in dentistry can be used in some countries by other dentists than specialists in radiology. The frequency of buying cone-beam computed tomography to examine patients is rapidly growing, thus knowledge of how to use it is very important. The aim was to compare the outcome of an investigation on the use of cone-beam computed tomography in Sweden with a previous Norwegian study, regarding specifically technical aspects. MATERIAL AND METHODS: The questionnaire contained 45 questions, including 35 comparable questions to Norwegian clinics one year previous. Results were based on inter comparison of the outcome from each of the two questionnaire studies. RESULTS: Responses rate was 71% in Sweden. There, most of cone-beam computed tomography (CBCT) examinations performed by dental nurses, while in Norway by specialists. More than two-thirds of the CBCT units had a scout image function, regularly used in both Sweden (79%) and Norway (75%). In Sweden 4% and in Norway 41% of the respondents did not wait for the report from the radiographic specialist before initiating treatment. CONCLUSIONS: The bilateral comparison showed an overall similarity between the two countries. The survey gave explicit and important knowledge of the need for education and training of the whole team, since radiation dose to the patient could vary a lot for the same kind of radiographic examination. It is essential to establish quality assurance protocols with defined responsibilities in the team in order to maintain high diagnostic accuracy for all examinations when using cone-beam computed tomography for patient examinations. PMID- 26904178 TI - Precipitation of Calcium Phosphates in the Presence of Collagen Type I on Four Different Bioactive Titanium Surfaces: an in Vitro Study. AB - OBJECTIVES: To compare the properties of calcium phosphate precipitation on four different bioactive surface preparations and one control surface in the simulated body fluid model with added collagen type I. MATERIAL AND METHODS: Blasted titanium discs were treated with four different surface modifications, alkali and heat, sodium fluoride, anodic oxidation and hydroxyapatite coating. The discs were divided into five groups where one group, the blasted, served as control. The discs were immersed in simulated body fluid and collagen for 24 h, 3 days, 1 week and 2 weeks and then analysed by optical interferometry, scanning electron microscopy/energy dispersive X-ray analysis and X-ray photoelectron spectroscopy. RESULTS: All surfaces show small precipitates after 3 days which with longer immersion times increase. After 2 weeks the surfaces were completely covered with precipitates, and Ca/P ratios were approximately 1.3, independently on surface preparation. The fluoridated discs showed significantly (P <= 0.05) higher degree of CaP after one week of immersion as compared to the other surface preparations. The collagen type I content increased with time, as reflected by increased nitrogen content. CONCLUSIONS: The results from this study indicate that a fluoridated titanium surface may favour precipitation of calcium phosphate in the presence of collagen type I, as compared to the other surface treatments of the present study. PMID- 26904180 TI - Mechanobiological Assessment of TMJ Disc Surfaces: Nanoindentation and Transmission Electron Microscopy. AB - OBJECTIVES: Temporomandibular disc is a mechanically robust fibrocartilage tissue exhibiting highly elastic compressive, shear, and tensile moduli with structurally dense extracellular matrix that supports functional loading of the joint. The aim of this study was to illustrate structural complexities of the superior and inferior disc surfaces, to demonstrate the robust mechanical ability of the disc as a whole may be due to depth-dependent regional/layered variation, and also to provide characterization data imperative for future tissue engineering efforts focused on restoring function to the joint. MATERIAL AND METHODS: Nanoindentation was used to assess tissue zones in conjunction with detailed Transmission Electron Microscopy to define structural attributes that influence the temporomandibular disc function. RESULTS: The disc architecture adjacent to the superior surface was shown to have three distinct regional segments within the interface layer: 1-a surface peripheral layer; 2-subsurface region; and 3-a layer of helical matrix bundles. The inferior surface displayed an interface layer (20 um) that showed limited cell populations with little depth dependent structural variation, a stiffer elastic modulus and reduced energy dissipation compared to the superior surface. These data indicate that the primary function of the inferior surface is resistance to compression rather than load distribution during joint motion. CONCLUSIONS: These are the first works that demonstrate that the superior central surface of the he temporomandibular disc is structured in depth-dependent isometric layers, each of which provides different mechanical function supporting the bulk tissue's properties. From a clinical perspective these data have potential to define regions susceptible to fatigue that may translate to diagnostic criteria to better define the stages of dysfunction. PMID- 26904181 TI - Application of Pont's Index to Lithuanian Individuals: a Pilot Study. AB - OBJECTIVES: A variety of diagnostic indices in orthodontics have been proposed to help in diagnosis and treatment planning. Pont's Index was established to predict ideal maxillary dental arch width from the sum of mesiodistal widths of four upper incisors. The aim of this study was to assess the applicability of Pont's Index to Lithuanian individuals. MATERIAL AND METHODS: The sample comprised 52 subjects (age range from 18 to 35 years) with normal occlusion. Measurements were obtained directly from plaster casts using a digital calliper. Ideal arch widths were calculated for each subject according to Pont's formulae, and the correlation coefficients were calculated between the measured and the calculated arch width values. RESULTS: Correlation between the measured width values and the corresponding values calculated according to Pont's Index was moderate in all cases, with correlation coefficients values ranging from 0.59 (mandible) to 0.64 (maxilla) in first premolar's area and 0.49 in both maxilla and mandible in first molar's area (P < 0.05). Appropriate index values for Lithuanian individuals were assessed to be 85.57 in premolars and 66.24 in molars area. CONCLUSIONS: According to the results of this study, there was no strong evidence to suggest that Pont's Index could be reliably used to predict ideal arch width values in Lithuanian individuals. PMID- 26904182 TI - Metastatic Tumours to the Oral Cavity: Report of Three Cases. AB - BACKGROUND: Metastatic tumours to the oral cavity from distant organs are uncommon and represent approximately 1 - 3% of all oral malignancies. Such metastases can occur to the bone or to the oral soft tissues. Almost any malignancy from any site is capable of metastasis to the oral cavity and a wide variety of tumours have been reported to spread to the mouth. METHODS: Careful examination of the oral cavity and a high degree of clinical suspicion as well as a multidisciplinary approach are suggested. RESULTS: In this article we present three patients, a female and two males with metastatic tumours to the oral cavity, who were referred to our Department. The primary tumours were invasive lobular breast carcinoma, gastric adenocarcinoma and small cell lung carcinoma respectively. CONCLUSIONS: Metastases to the oral cavity are quite uncommon among population. They usually present with symptoms similar to odontogenic infections and benign tumours, causing a delayed diagnosis and treatment. PMID- 26904184 TI - Assemblages of saproxylic beetles on large downed trunks of oak. AB - Old living oaks (Quercus robur) are known as a very species-rich habitat for saproxylic beetles, but it is less clear to what extent such veteran trees differ from an even rarer feature: downed trunks of large oaks. In this study, we set out to sample this habitat, using window traps, with two aims: (1) to describe the variation of assemblages among downed trunks of different type and (2) to compare beetles on downed oaks with data from veteran standing trees. The results showed that trunk volume and sun exposure better explained assemblages as well as species numbers on downed trunks than did decay stage. Furthermore, species classified as facultative saproxylic species showed weak or no differentiation among downed trunks. Species with different feeding habits showed no apparent differentiation among downed trunks. Furthermore, species composition on dead, downed oak trunks differed sharply from that of living, veteran oaks. Wood or bark feeders were more common on veterans than downed trunks, but there was no difference for those species feeding on fungi or those feeding on insects and their remains. In conclusion, for a successful conservation of the saproxylic beetle fauna it is important to keep downed oak trunks, and particularly large ones, in forest and pastures as they constitute a saproxylic habitat that differs from that of living trees. PMID- 26904183 TI - Chiropractors' perception of occupational stress and its influencing factors: a qualitative study using responses to open-ended questions. AB - BACKGROUND: Job stress and emotional exhaustion have been shown to have a negative impact on the helping professional. The development and causal relations of job stress and emotional exhaustion are rather unclear in the chiropractic profession. The objective of this study is to understand the main sources of occupational stress and emotional exhaustion among doctors of chiropractic. METHODS: Analysis of the written responses to web-based open-ended questionnaire was performed using an interpretive research methodology. Additionally, cross tabulation and Chi square statistical tests were conducted to match and couple the demographic data with the categorical themes. RESULTS: Fourteen professional stress categories emerged from the 970 completed surveys. "Managed Care Organization regulation", "Managed Care reimbursement" and "Scope of Practice Issues" were the most common stressors that negatively influenced chiropractors' professional and personal lives. The results of the categorical analysis suggests that age, marital status, number of years in practice and location of practice may have an influence on the category of stress reported by chiropractors. CONCLUSIONS: The qualitative approach revealed common, conventional and culture specific job stressors in doctors of chiropractic. Notably, these findings suggest an association between third-party payer influences (increased regulation/decreased reimbursement) with that of increased job stress. Further research will be undertaken to refine the stress and satisfaction parameters and address stress interventions. PMID- 26904185 TI - Eggshell pigment composition covaries with phylogeny but not with life history or with nesting ecology traits of British passerines. AB - No single hypothesis is likely to explain the diversity in eggshell coloration and patterning across birds, suggesting that eggshell appearance is most likely to have evolved to fulfill many nonexclusive functions. By controlling for nonindependent phylogenetic associations between related species, we describe this diversity using museum eggshells of 71 British breeding passerine species to examine how eggshell pigment composition and concentrations vary with phylogeny and with life-history and nesting ecology traits. Across species, concentrations of biliverdin and protoporphyrin, the two main pigments found in eggshells, were strongly and positively correlated, and both pigments strongly covaried with phylogenetic relatedness. Controlling for phylogeny, cavity-nesting species laid eggs with lower protoporphyrin concentrations in the shell, while higher biliverdin concentrations were associated with thicker eggshells for species of all nest types. Overall, these relationships between eggshell pigment concentrations and the biology of passerines are similar to those previously found in nonpasserine eggs, and imply that phylogenetic dependence must be considered across the class in further explanations of the functional significance of avian eggshell coloration. PMID- 26904186 TI - Metabarcoding of fungal communities associated with bark beetles. AB - Many species of fungi are closely allied with bark beetles, including many tree pathogens, but their species richness and patterns of distribution remain largely unknown. We established a protocol for metabarcoding of fungal communities directly from total genomic DNA extracted from individual beetles, showing that the ITS3/4 primer pair selectively amplifies the fungal ITS. Using three specimens of bark beetle from different species, we assess the fungal diversity associated with these specimens and the repeatability of these estimates in PCRs conducted with different primer tags. The combined replicates produced 727 fungal Operational Taxonomic Units (OTUs) for the specimen of Hylastes ater, 435 OTUs for Tomicus piniperda, and 294 OTUs for Trypodendron lineatum, while individual PCR reactions produced on average only 229, 54, and 31 OTUs for the three specimens, respectively. Yet, communities from PCR replicates were very similar in pairwise comparisons, in particular when considering species abundance, but differed greatly among the three beetle specimens. Different primer tags or the inclusion of amplicons in separate libraries did not impact the species composition. The ITS2 sequences were identified with the Lowest Common Ancestor approach and correspond to diverse lineages of fungi, including Ophiostomaceae and Leotiomycetes widely found to be tree pathogens. We conclude that Illumina MiSeq metabarcoding reliably captures fungal diversity associated with bark beetles, although numerous PCR replicates are recommended for an exhaustive sample. Direct PCR from beetle DNA extractions provides a rapid method for future surveys of fungal species diversity and their associations with bark beetles and environmental variables. PMID- 26904187 TI - The transcriptomic basis of tissue- and nutrition-dependent sexual dimorphism in the beetle Onthophagus taurus. AB - Sexual dimorphism accounts for a large fraction of intraspecific diversity. However, not all traits are equally sexually dimorphic; instead, individuals are mosaics of tissues that vary in their ability to exhibit dimorphism. Furthermore, the degree of a trait's sexual dimorphism is frequently environment-dependent, with elaborate sexual dimorphism commonly being restricted to high nutritional conditions. Understanding the developmental basis and evolution of condition dependent sexual dimorphism can be critically informed by determining - across tissues and nutritional conditions - what sex-biased genes are deployed and how they interact and translate into functional processes. Indeed, key theories concerning the evolution of condition-dependent sexually dimorphic traits rest on assumptions regarding their developmental genetic underpinnings, yet, have largely gone unexamined by empirical studies. Here, we provide such evidence by investigating the transcriptomic basis of tissue- and nutrition-dependent sexual dimorphism in the bull-headed dung beetle Onthophagus taurus. Our findings suggest (1) that generating morphological sexual dimorphism requires sex-biased gene expression in and developmental remodeling of both sexes, regardless of which sex exhibits externally visible trait exaggeration, (2) that although sexually dimorphic phenotypes are comprised of traits underlain by independent repertoires of sex-biased gene expression, they act similarly at a functional level, and (3) that sexual dimorphism and condition-dependence share common genetic underpinnings specifically in sexually-selected traits. PMID- 26904188 TI - Quality of life after subtotal gastrectomy for gastric cancer: Does restoration method matter? - A retrospective cohort study. AB - INTRODUCTION: The aim of this study was to evaluate the impact on the quality of life (QoL) status of three gastrointestinal continuity restoration methods following a subtotal gastrectomy in patients with gastric cancer. METHODS: QoL data from 153 patients were obtained and evaluated in this retrospective cross sectional case series study. A list of patients who responded to questionnaires on QoL was stratified into three arms based on which gastrointestinal continuity restoration method was used - Billroth I (n = 37), Roux-en-Y (n = 15), and Balfour (n = 101). RESULTS: The mean global health status scores for the patients following the Billroth I, Roux-en-Y and Balfour reconstructive surgery arms were 62 +/- 20.09, 61 +/- 24.08 and 56 +/- 21.2, respectively, (p = 0.182). The mean scores of the functional scales were not lower than 60 in any of the patient groups. For physical, role, cognitive, social functional scales, the Billroth I method had the best mean QoL score. Comparisons of the global QoL, functional activities, and majority of the postgastrectomy symptom scores at different time points after the surgeries (6-12 months vs > 1 year) did not reveal major significant differences between the groups. However, the results highlighted trends and ranked the gastrointestinal continuity restoration methods over time. CONCLUSIONS: The best QoL scores were obtained from the patients who underwent the Billroth I surgery. The Roux-en-Y method was better than the Balfour method 6 12 months after surgery. However, the Balfour method was better than the Roux-en Y after one year. Further prospective randomized controlled trials are needed. PMID- 26904189 TI - Intramural oesophageal dissection as an unusual presentation of chest pain: A case report. AB - INTRODUCTION: Intramural oesophageal dissection (IOD) is a rare clinical condition and there is a paucity of information regarding the appropriate diagnosis and management. It is described as bleeding in the submucosal plane of the oesophagus, and has various documented causes. PRESENTATION OF CASE: We report a case of a 73 year old female who developed IOD. She presented with severe chest pain. Subsequent imaging revealed IOD and haematoma formation. This was confirmed on oesophagogastroduodenoscopy (OGD). She was on a bisphosphonate for her osteoporosis, as well as having age-related dysmotility of her oesophagus on manometric studies. She was also taking fish oil. Treatment was conservative and the patient was discharged with proton pump inhibitors and follow up. DISCUSSION: Spontaneous haematoma formation and IOD resulted likely from a combination of the anticoagulant effect of fish oil and oesophageal dysmotility. Bisphosphonates also have some well documented gastrointestinal side effects involving mucosal damage. The possibility that the concurrent use of bisphosphonate led to a pre-existing ulcer which could have contributed to the development of IOD in this patient should be considered. CONCLUSION: spontaneous IOD can occur in elderly patients who are anticoagulated. Fish oil has not been previously reported as having an association with IOD. This is the first known reported case of spontaneous IOD occurring in association with concurrent use of a bisphosphonate and fish oil. IOD is a rare disorder, and any anticoagulated patients presenting with severe chest pain may need careful investigation prior to definitive management. PMID- 26904190 TI - Rare benign mixed tumour of the upper lip: A case report. AB - BACKGROUND: Chondroid syringomas (CS) are rare benign mixed tumours. Clinical differentiation can be misleading due to the silent presentation, with only histopathological findings confirming the diagnosis. CASE REPORT: A 23-year-old Caucasian gentleman presented with an eighteen month history of increasing size of his exophytic upper lip mass. The initial clinical impression was thought to be related to the skin. Following a punch biopsy, histopathology confirmed appearance in keeping with part of a chondroid syringoma with subsequent excision of the lesion. DISCUSSION: CS present as a slow-growing, asymptomatic, non tender, nonulcerated, smooth, firm subcutaneous, or intradermal nodule and can range from 0.5 to 3.0 cm, predominantly occurring in the head and neck region in patients aged above 35 years with a male predication. The most effective diagnostic method is microscopic examination. The gold standard treatment modality is by complete excision with a margin of normal tissue in order to examine the histopathologic features and prevent recurrence. CONCLUSION: CS should be included as a differential diagnosis of facial subcutaneous skin lesions in middle aged male patients. Careful evaluation, with a view of total excision and adequate surgical margin will enable diagnostic confirmation, whilst maintaining the aesthetic and functional unit. PMID- 26904191 TI - An 8-YEAR analysis of bone tumours in a Caribbean island. AB - BACKGROUND: An epidemiologic analysis of bone tumours in Trinidad & Tobago. METHODS: A retrospective analysis of primary and secondary bone tumours, site of origin and demographic data was conducted. RESULTS: 63 bone tumours were analysed and included 27 primary benign (43%), 12 primary malignant (19%), 19 metastatic (30%) and 5 by contiguous spread (8%). The most common malignant primary tumour was the osteosarcoma (n = 7), originating from the femur in mostly males in the 11-20 age group. There was 1 chondrosarcoma, 2 fibrosarcomas and 2 plasmacytomas. Benign tumours consisted of 8 osteochondromas, 2 osteomas, 3 giant cell tumours, 3 bone cysts and 11 cases of fibrous dysplasia. CONCLUSION: Bone tumours are rare with a low incidence of 1.125 per 100,000 population annually and malignant tumours being even rarer at an incidence of 0.18 per 100,000 population annually. There is need for better documentation and data registries in Trinidad and Tobago. PMID- 26904192 TI - Bilateral posterior shoulder dislocation after electrical shock: A case report. AB - INTRODUCTION: Posterior dislocation of the shoulder is a rare and commonly missed injury. Unilateral dislocations occur mostly due to trauma. Bilateral posterior shoulder dislocations are even more rare and result mainly from epileptic seizures. Electrical injury is a rare cause of posterior shoulder dislocation. Injury mechanism in electrical injury is similar to epileptic seizures, where the shoulder is forced to internal rotation, flexion and adduction. PRESENTATION OF CASE: This report presents a case of bilateral posterior shoulder dislocation after electrical shock. We were able to find a few individual case reports describing this condition. The case was acute and humeral head impression defects were minor. Our treatment in this case consisted of closed reduction under general anesthesia and applying of orthoses which kept the shoulders in abduction and external rotation. A rehabilitation program was begun after 3 weeks of immobilization. After 6 months of injury the patient has returned to work. 20 months postoperatively, at final follow-up, he was painless and capable of performing all of his daily activities. DISCUSSION: The amount of bilateral shoulder dislocations after electrical injury is not reported but is known to be very rare. The aim of this case presentation is to report an example for this rare entity, highlight the difficulties in diagnosis and review the treatment options. CONCLUSION: Physical examination and radiographic evaluation are important for quick and accurate diagnosis. PMID- 26904193 TI - The role of non-technical skills in surgery. AB - Non-technical skills are of increasing importance in surgery and surgical training. A traditional focus on technical skills acquisition and competence is no longer enough for the delivery of a modern, safe surgical practice. This review discusses the importance of non-technical skills and the values that underpin successful modern surgical practice. This narrative review used a number of sources including written and online, there was no specific search strategy of defined databases. Modern surgical practice requires; technical and non-technical skills, evidence-based practice, an emphasis on lifelong learning, monitoring of outcomes and a supportive institutional and health service framework. Finally these requirements need to be combined with a number of personal and professional values including integrity, professionalism and compassionate, patient-centred care. PMID- 26904194 TI - "Less is more": Non operative management of short term superior mesenteric artery syndrome. AB - INTRODUCTION: Superior mesenteric artery (SMA) syndrome is a relatively rare aetiology of proximal intestinal obstruction. This is caused by narrowing of vascular angle of SMA and aorta compressing the third part of the duodenum (D3). Predisposing factors may include precipitous weight loss, corrective spinal surgery or repair of an aortic aneurysm. PRESENTATION OF CASE: A 53 year old male presented to our department with worsening post-prandial vomiting and epigastric pain for last three months. One examination, epigastric region was distended with succussion splash on abdominal auscultation. History did not include any predisposing factor. CT scan showed narrow angle of 12.77 degrees between SMA and aorta owing to the compression of D3. Since onset of vomiting and resultant poor oral intake, he had lost 11 kg of his usual body weight. After gastric decompression, nasojejunal enteral feeding was started. Diet was progressed to oral feedings gradually and following return to his baseline weight, he continued to be free of symptoms in follow-up visits. DISCUSSION: Although there are recognised predisposing factors but sometimes aetiology remains idiopathic. SMA syndrome should initially be managed non-operatively with gastric decompression, correction of water and electrolyte imbalance, and hemodynamic instability. Regaining weight helps increasing vascular space between SMA and D3 thus relieving obstruction. Persistence of symptoms beyond 3-4 weeks warrants surgical intervention. CONCLUSION: Non operative management with nutritional supplementation remains the first line of therapy. PMID- 26904195 TI - Unaware of a large leiomyoma: A case report with respect to unusual symptoms of large leiomyomas. AB - INTRODUCTION: Uterine leiomyoma, which arises from uterine smooth muscle, is the most common benign gynecologic tumor of the female pelvis. Clinically, these leiomyomas are diagnosed in approximately 25% of women, the prevalence increases during reproductive age, decreases after menopause, and they are rare in adolescents. In addition to uterine leiomyoma, there are also extrauterine leiomyomas. PRESENTATION OF CASE: A 48-year-old multiparous woman visited our outpatient clinic for routine control. She had no symptoms or complaints. Her last health service visit was over 5 years ago, in which she was told that she had a small uterine leiomyoma, which did not require further management. Abdominal examination revealed a large mass extended above the umbilicus, and there was no abdominal tenderness. Abdominal ultrasonography showed a large solid mass occupying the abdomen. Routine laboratory test results were normal, except the hemoglobin level, which was 7.88 g/dl. A total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed. The final diagnosis was a 17-cm, 3985-g intramural, myomatous, cellular leiomyoma that occurred without secondary changes, necrosis, cellular atypia, or mitosis. DISCUSSION: The most common presenting symptoms of large uterine leiomyomas are abnormal bleeding, dysmenorrhea, pelvic pain, and tumor bulk-related signs. Moreover, there are unusual symptoms or clinical manifestations such as acute edema, thrombosis, ulcer, plethora, calcified pelvic masses, hematometra, severe pulmonary hypertension, and respiratory failure; hence, they can be even life threatening. CONCLUSION: Patients might have no symptoms or might be unaware of the presence of a large uterine leiomyoma, as in our case; however, large leiomyomas have various unusual symptoms in addition to the common ones. These symptoms should not be disregarded or underestimated. PMID- 26904196 TI - Merkel cell carcinoma of unknown primary site; case presentation and review of the literature. AB - Merkel cell carcinoma (MCC) is a rare skin malignancy associated with sun exposure and considered as a Neuroendocrine Tumor due to its characteristic histologic features. However there is increasing number of reports of Unknown Primary MCC's (UPMCC). Although initially UPMCC was considered a variant of known primary MCC, there is growing evidence that it could represent a different clinical entity. We present the case of a 60 year-old male patient who was referred to our department for surgical management of lymph node disease for UPMCC. The patient had undergone excisional biopsy of an inguinal lump, which was found to be an infiltrated lymph node by MCC. The patient underwent full imaging staging including a PET/CT, which failed to identify a primary site, and revealed only intra-abdominal lymph node disease. The patient underwent extended retroperitoneal and inguinal lymph node dissection and remains free of recurrence 16 months postoperatively. PMID- 26904197 TI - Assessment of iodine status among pregnant women in a rural community in ghana - a cross sectional study. AB - BACKGROUND: Pregnancy is associated with parallel increase in both iodine, and thyroid hormone requirements suggesting that, there may be the need for additional iodine intake during this period to prevent potential iodine insufficiency. Medically, an excess or reduced intake of this micronutrient has negative effects on the individual's health. This study aimed at identifying the pattern of iodine levels among pregnant women at Kissi, Ghana. METHOD: A cross sectional study was carried out among pregnant women on antenatal care at Kissi Health Centre (KHC) which serves the rural town with a population of about 4,500, located in the Komenda/Edina/Eguafo/Abirem (KEEA) municipality in the Central Region of Ghana. Demographic information, iodated salt usage and other pertinent information such as tobacco use were captured using a questionnaire. In addition, urine iodine concentration was estimated through the Ammonium per sulfate method after collecting on-the-spot urine samples. RESULTS: Prevalence of iodine deficiency in pregnant women was 42.5 %. Of the 80 participants who were on iodized salt, only 16.25 % had mild iodine deficiency with none suffering from moderate or severe iodine deficiency. Of the 40 participants who did not use iodized salt, 35 %, 30 %, and 30 % suffered from severe, moderate and mild iodine deficiency respectively. CONCLUSION: The high prevalence of iodine deficiency reported in this study suggests that urgent national measures are required to correct iodine insufficiency in pregnant women in these communities. PMID- 26904198 TI - Reversal of severe cognitive impairment following medical treatment of cystic invasive giant prolactinoma. AB - Giant prolactinomas are rare tumours of the pituitary, which typically exceed 40 mm in their largest dimension. Impairment of higher cognitive function has been noted post-operatively after transcranial surgery and as a long-term consequence of the radiotherapy treatment. However, there has been little that is reported on such disturbances in relation to the tumour per se, and to our knowledge, there has been none in terms of responsivity to dopamine agonist therapy and shrinkage in these tumours. We present a case of successful restoration of severely impaired cognitive functions achieved safely after significant adenoma involution with medical treatment alone. LEARNING POINTS: Giant prolactinomas can be present with profound cognitive defects.Dopamine agonists remain in the mainstay first line treatment of giant prolactinomas.Mechanisms of the reversible cognitive impairment associated with giant prolactinoma treatment appear to be complex and remain open to further studies.Young patients with giant prolactinomas mandate genetic testing towards familial predisposition. PMID- 26904199 TI - pNET co-secreting GHRH and calcitonin: ex vivo hormonal studies in human pituitary cells. AB - Acromegaly due to ectopic GHRH secretion from a neuroendocrine tumor (NET) is rare and comprises <1% of all acromegaly cases. Herein we present a 57-year-old woman with clinical and biochemical features of acromegaly and a 6 cm pancreatic NET (pNET), secreting GHRH and calcitonin. Following surgical resection of the pancreatic tumor, IGF1, GH and calcitonin normalized, and the clinical features of acromegaly improved. In vitro studies confirmed that the tumor secreted large amounts of both GHRH and calcitonin, and incubation of pNET culture-derived conditioned media stimulated GH release from a cultured human pituitary adenoma. This is a unique case of pNET secreting both GHRH and calcitonin. The ability of the pNET-derived medium to stimulate in vitro GH release from a human pituitary cell culture, combined with the clinical and hormonal remission following tumor resection, confirmed the ectopic source of acromegaly in this patient. LEARNING POINTS: Signs, symptoms and initial work-up of acromegaly due to ectopic GHRH secretion are similar to pituitary-dependent acromegaly. However, if no identifiable pituitary lesion is found, somatostatin receptor scan and further imaging (CT, MRI) should be performed.Detection of GHRH in the blood and in the tumor-derived medium supports the diagnosis of ectopic GHRH secretion.Functional bioactivity of pNET-secreted GHRH can be proved in vitro by releasing GH from human pituitary cells. PMID- 26904200 TI - Distribution of innate efflux-mediated aminoglycoside resistance among different Achromobacter species. AB - Achromobacter spp. are emerging respiratory pathogens in cystic fibrosis patients. Since 2013 the genus Achromobacter includes 15 species for which innate antibiotic resistance is unknown. Previously the AxyXY-OprZ efflux system has been described to confer aminoglycoside (AG) resistance in A. xylosoxidans. Nevertheless, some Achromobacter spp. strains are susceptible to AG. This study including 49 Achromobacter isolates reveals that AG resistance is correlated with different Achromobacter spp. It is noteworthy that the axyXY-oprZ operon is detected only in AG-resistant species, including the most frequently encountered in cystic fibrosis patients: A. xylosoxidans, A. ruhlandii, A. dolens and A. insuavis. PMID- 26904201 TI - Hepatitis E virus is the leading cause of acute viral hepatitis in Lothian, Scotland. AB - Acute viral hepatitis affects all ages worldwide. Hepatitis E virus (HEV) is increasingly recognized as a major cause of acute hepatitis in Europe. Because knowledge of its characteristics is limited, we conducted a retrospective study to outline demographic and clinical features of acute HEV in comparison to hepatitis A, B and C in Lothian over 28 months (January 2012 to April 2014). A total of 3204 blood samples from patients with suspected acute hepatitis were screened for hepatitis A, B and C virus; 913 of these samples were also screened for HEV. Demographic and clinical information on patients with positive samples was gathered from electronic patient records. Confirmed HEV samples were genotyped. Of 82 patients with confirmed viral hepatitis, 48 (59%) had acute HEV. These patients were older than those infected by hepatitis A, B or C viruses, were more often male and typically presented with jaundice, nausea, vomiting and/or malaise. Most HEV cases (70%) had eaten pork or game meat in the few months before infection, and 14 HEV patients (29%) had a recent history of foreign travel. The majority of samples were HEV genotype 3 (27/30, 90%); three were genotype 1. Acute HEV infection is currently the predominant cause of acute viral hepatitis in Lothian and presents clinically in older men. Most of these infections are autochthonous, and further studies confirming the sources of infection (i.e. food or blood transfusion) are required. PMID- 26904204 TI - Quantitative imaging of chronic obstructive pulmonary disease-moving towards clinical application. PMID- 26904203 TI - Factors associated with BMI, underweight, overweight, and obesity among adults in a population of rural south India: a cross-sectional study. AB - BACKGROUND: Overweight, obesity, and related chronic diseases are becoming serious public health concerns in rural areas of India. Compounded with the existing issue of underweight, such concerns expose the double burden of disease and may put stress on rural healthcare. The purpose of this article was to present the prevalence and factors associated with underweight, overweight, and obesity in an area of rural south India. METHODS: During 2013 and 2014, a random sample of adults aged 20-80 years were selected for participation in a cross sectional study that collected information on diet (using a food frequency questionnaire), physical activity (using the Global Physical Activity Questionnaire), socioeconomic position (using a wealth index), rurality (using the MSU rurality index), education, and a variety of descriptive factors. BMI was measured using standard techniques. Using a multivariate linear regression analysis and multivariate logistic regression analyses, we examined associations between BMI, overweight, obesity, and underweight, and all potential risk factors included in the survey. RESULTS: Age and sex-adjusted prevalence of overweight, obesity class I, and obesity class II were 14.9, 16.1, and 3.3 % respectively. Prevalence of underweight was 22.7 %. The following variables were associated with higher BMI and/or increased odds of overweight, obesity class I, and/or obesity class II: Low physical activity, high wealth index, no livestock, low animal fat consumption, high n-6 polyunsaturated fat consumption, television ownership, time spent watching television, low rurality index, and high caste. The following variables were associated with increased odds of underweight: low wealth index, high rurality index, and low intake of n-6 PUFAs. CONCLUSION: Underweight, overweight, and obesity are prevalent in rural regions of southern India, indicating a village-level dual burden. A variety of variables are associated with these conditions, including physical activity, socioeconomic position, rurality, television use, and diet. To address the both underweight and obesity, policymakers must simultaneously focus on encouraging positive behaviour through education and addressing society-level risk factors that inhibit individuals from achieving optimal health. PMID- 26904205 TI - Is chordal-preserving mitral valve replacement superior to valve repair in appropriately selected patients? PMID- 26904206 TI - Aspiration thrombectomy in 2015: a TOTAL defeat? PMID- 26904207 TI - Bronchodilator response in adults with bronchiectasis: correlation with clinical parameters and prognostic implications. AB - BACKGROUND: Bronchial dilation testing is an important tool to assess airway reversibility in adults with bronchiectasis. This study aims to investigate the association of bronchodilator response (BDR) and clinical parameters in bronchiectasis, and the utility of BDR to indicate lung function decline and risks of bronchiectasis exacerbations (BEs). METHODS: We recruited 129 patients with clinically stable bronchiectasis. Baseline measurements included assessment of sputum inflammation and matrix metalloproteinase-8 and -9, sputum bacterial culture, spirometry, bronchial dilation test (for baseline FEV1 less than 80% predicted only) and chest high-resolution computed tomography (HRCT). Bronchiectasis patients were followed-up for 1 year to determine the incidence of BEs and lung function trajectories. Significant BDR was defined as FEV1 improvement from pre-dose value by at least 200 mL and 12%. Clinical trial registry No.: NCT01761214; URL: www.clinicaltrials.gov. RESULTS: BDR was negatively correlated with baseline FEV1 percentage predicted, but not blood or sputum eosinophil count. Significant BDR was not associated with greater proportion of never-smokers, poorer past history, greater HRCT scores, poorer diffusing capacity or increased sputum matrix metalloproteinases (all P>0.05). There was a trend towards higher bronchiectasis severity index (BSI) and greater proportion of patients with Pseudomonas aeruginosa isolation or infection. Significant BDR at baseline was linked to poorer spirometry, but not more rapid lung function decline, throughout follow-up. Patients with significant BDR demonstrated non-significantly lower risks of experiencing the first BEs than those without (P=0.09 for log-rank test). CONCLUSIONS: Significant BDR is associated with poorer lung function compared with non-significant BDR. Whether BDR predicts future risks of BEs needs to be tested in a larger cohort. PMID- 26904208 TI - A novel method for lymphadenectomy along the left laryngeal recurrent nerve during thoracoscopic esophagectomy for esophageal carcinoma. AB - BACKGROUND: Due to limited space in the left upper mediastinum, complete dissection of lymph nodes (LN) along left recurrent laryngeal nerve (RLN) is difficult. We herein present a novel method for lymphadenectomy along the left RLN during thoracoscopic esophagectomy in the semi-prone position for esophageal carcinoma. The method, suspension the esophagus and push aside trachea, allows en bloc lymphadenectomy along the left RLN from the below aortic arch to the thoracic inlet. METHODS: Between September 2014 and September 2015, a total of 110 consecutive patients with esophageal carcinoma were treated with thoraco laparoscopic esophagectomy with cervical anastomosis in the semi-prone position. Outcomes between those who received surgery with the novel method and conventional surgery were compared. RESULTS: Fifty patients underwent the novel method and sixty received conventional surgery. The operative field around the left RLN was easier to explore with the novel method. The estimated blood loss was less (23.7+/-8.2 vs. 34.2+/-10.3 g, P=0.001), and the number of harvested LNs along the left RLN was greater (6.4+/-3.2 vs. 4.1+/-2.8 min, P=0.028) in the novel method group, while the duration of lymphadenectomy along left RLN was longer in the novel method group (28.2+/-3.9 vs. 20.3+/-2.8 min, P=0.005). The rate of hoarseness in the novel and conventional groups was 10% and 16.7%, respectively. No significant difference in postoperative morbidity related to the left RLN was noted between the groups. CONCLUSIONS: The novel method during semi prone esophagectomy for esophageal carcinoma is associated with better surgeon ergonomics and operative exposure. PMID- 26904209 TI - Video-assisted thoracic surgery for pulmonary sequestration: a safe alternative procedure. AB - BACKGROUND: Pulmonary sequestration (PS), a rare congenital anatomic anomaly of the lung, is usually treated through resection by a conventional thoracotomy procedure. The efficacy and safety of video-assisted thoracic surgery (VATS) in PS treatment has seldom been evaluated. To address this research gap, we assessed the efficacy and safety of VATS in the treatment of PS in a large Chinese cohort. METHODS: We retrospectively reviewed 58 patients with PS who had undergone surgical resection in our department between January 2003 and April 2014. Of these patients, 42 (72.4%) underwent thoracotomy, and 16 (27.6%) underwent attempted VATS resection. Clinical and demographic data, including patients' age, sex, complaints, sequestration characteristics, approach and procedures, operative time, resection range, blood loss, drainage volume, chest tube duration, hospital stay, and complications were collected, in addition to short term follow-up data. RESULTS: Of the 58 participating patients, 55 accepted anatomic lobectomy, 2 accepted wedge resection, and 1 accepted left lower lobectomy combined with lingular segmentectomy. All lesions were located in the lower lobe, with 1-4 aberrant arteries, except one right upper lobe sequestration. Three cases (18.8%) in the VATS group were converted to thoracotomy because of dense adhesion (n=1), hilar fusion (n=1), or bleeding (n=1). No significant differences in operative time, postoperative hospital stay, or perioperative complications were observed between the VATS and thoracotomy groups, although the VATS patients had less blood loss (P=0.032), a greater drainage volume (P=0.001), and a longer chest tube duration (P=0.001) than their thoracotomy counterparts. CONCLUSIONS: VATS is a viable alternative procedure for PS in some patients. Simple sequestration without a thoracic cavity or hilum adhesion is a good indication for VATS resection, particularly for VATS anatomic lobectomy. Thoracic cavity and hilum adhesion remain a challenge for VATS. PMID- 26904210 TI - Awake extracorporeal membrane oxygenation in patients with severe postoperative acute respiratory distress syndrome. AB - BACKGROUND: A clinical trial of extracorporeal membrane oxygenation (ECMO) as an alternative ventilator tool is being performed as a new indication for ECMO. The purpose of this study was to evaluate the feasibility of awake ECMO to increase the success rate of weaning patients from ECMO and ventilator care during treatment of postoperative severe acute respiratory distress syndrome (ARDS). METHODS: We retrospectively analyzed the clinical reports of 10 patients who underwent awake ECMO due to postoperative ARDS between August 2012 and May 2015. We analyzed patient history, the partial arterial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio, and patient outcome. RESULTS: Seven patients (70%) were weaned from ECMO without difficulty; one patient failed to maintain awake ECMO, was re-intubated after 2 days of awake ECMO, and was re tried on awake ECMO after 4 days of ventilator care. We weaned that patient from ECMO 2 days later. We weaned a total of eight patients (80%) from awake ECMO. The ECMO duration of surviving patients was 9.13+/-2.2 days (range, 6-12 days), and mean ventilator use duration was 6.8+/-4.7 days (range, 2-16 days). Two cases failed awake ECMO and died due to disease aggravation. CONCLUSIONS: Awake ECMO was a useful weaning strategy after severe postoperative ARDS, as it avoids long duration use of mechanical ventilation. Additionally, it is possible for patients to breathe spontaneously, which might prevents respiratory muscle dystrophy. PMID- 26904211 TI - Outcomes of total cavopulmonary connection for single ventricle palliation. AB - BACKGROUND: The aim of this study was to review the early and mid-term outcomes of the total cavopulmonary connection (TCPC) procedure and evaluate risk factors for prolonged pleural effusions. METHODS: The clinical records of 82 consecutive patients, who underwent a TCPC operation between January 2008 and December 2013, were reviewed for incidence of prolonged pleural effusions, duration of ventilation time and pleural drainage, length of intensive care unit (ICU) stay, and early and mid-term morbidity and mortality. RESULTS: The median age at surgery was 3.0 years. The main single ventricle diagnoses included 18 cases of a double-inlet single ventricle, 17 cases of heterotaxy, 16 cases of tricuspid atresia, 4 cases of mitral atresia, 12 cases of unbalanced complete atrioventricular canal (CAVC), 5 cases of double-outlet right ventricle (DORV) combined with ventricular septal defect (VSD) and pulmonary stenosis (PS), 4 cases of transposition of the great arteries (TGA) combined with VSD and PS, 4 cases of corrected transposition of great arteries (cTGA) combined VSD and PS, and 2 cases of criss-cross heart. Preoperative mean pulmonary artery pressure (mPAP) was 13.66+/-2.21 mmHg with 23.2% (n=19) higher than 15 mmHg. A total of 61 (74.4%) patients underwent a fenestration. The perioperative mortality was 4.9%. The median duration of pleural effusion was 10 days (range, 3-80 days), and prolonged pleural effusions occurred in 16 (19.5%) patients. Multivariable analysis revealed that mPAP >15 mmHg was independently associated with prolonged pleural effusions (OR, 8.33; 95% CI, 2.33-29.74; P=0.001), and creation of a fenestration was associated with decreased odds of effusion (OR, 0.21; 95% CI, 0.06-0.74; P=0.015). Five-year estimated Kaplan-Meier survival of two-stage TCPC was significantly higher than that of one-stage group(96.7% vs. 79.7%, P=0.023). Patients with heterotaxy or obstructed totally anomalous pulmonary venous connection (TAPVC) had significantly worse mid-term survival. CONCLUSIONS: Staged TCPC improved the early and mid-term survival of patients with a single ventricle. mPAP >15 mmHg was independently associated with prolonged pleural effusions and a fenestration significantly associated with a lower odds of effusion. PMID- 26904212 TI - Role of medical thoracoscopy in the treatment of tuberculous pleural effusion. AB - BACKGROUND: Fibrous tuberculous pleural effusion (TPE) represents common disease in tuberculous clinic. Medical thoracoscopy has been used to treat pleural empyema and shown promising outcomes, but data of its use in multiloculated and organized TPE remains limited to know. METHODS: The study was performed on 430 cases with TPE. The cases were divided into free-flowing, multiloculated effusion and organized effusion group. Each group was subdivided into two or three types of therapeutic approaches: ultrasound guided pigtail catheter, large-bore tube chest drainage and medical thoracoscopy. Patients with multiloculated or organized effusions received streptokinase, introduced into the pleural cavity via chest tubes. The successful effectiveness of the study was defined as duration of chest drainage, time from treatment to discharge days and no further managements. RESULTS: Patients with organized effusion were older than those with free-flowing effusion and incidence of organized effusion combined with pulmonary tuberculosis (PTB) was higher than those of multiloculated effusion and free flowing effusion respectively. Positive tuberculosis of pleural fluid culture was higher in organized effusion than that in free-flowing effusion. Sputum positive for acid-fast bacillus (AFB) in organized effusion was higher than that in multiloculated effusion and free-flowing effusion. Medical thoracoscopy showed significant efficacy in the group of multiloculated effusion and organized effusion but free-flowing effusion. No chronic morbidity and mortality related to complications was observed. CONCLUSIONS: Medical thoracoscopy was a safe and successful method in treating multiloculated and organized TPE. PMID- 26904213 TI - Prosthetic graft interposition of the brachiocephalic veins or superior vena cava combined with resection of malignant tumours: graft patency and risk factors for graft occlusion. AB - BACKGROUND: We aimed to assess graft patency in patients undergoing prosthetic graft interposition of the brachiocephalic veins (BCVs) or the superior vena cava (SVC) combined with resection of malignant tumours. METHODS: A retrospective analysis was conducted on 16 patients who underwent prosthetic graft interposition of the BCVs or the SVC between 1998 and 2012. RESULTS: Among a total of 20 grafts in 16 patients (unilateral graft interposition in 12, bilateral graft interposition in 4), 8 grafts were occluded in 8 patients. Overall graft patency rate was 64.6%, 42.4% at the 2- and 5-year follow-up. Graft patency rate of the left BCV was significantly lower than that of the right BCV or the SVC (2-year patency, 38.1% vs. 81.8%, P=0.024). In univariate analysis, the superior anastomosis site [left BCV vs. right BCV; hazard ratio (HR) =2.312; 95% confidence interval (CI), 1.015-5.265; P=0.046], the inferior anastomosis site (right atrial appendage vs. SVC; HR =2.409; 95% CI, 1.124-5.161; P=0.024), and interruption of warfarin (HR =5.015; 95% CI, 1.106-22.734; P=0.037) were significant risk factors for graft occlusion. Graft occlusive symptoms were identified in 4 patients who underwent unilateral graft interposition. CONCLUSIONS: Prosthetic graft interposition between the left BCV and the right atrial appendage resulted in a significant rate of graft occlusion. Prosthetic graft interposition of the bilateral BCVs and long-term warfarin therapy may be necessary to prevent graft occlusive symptoms. PMID- 26904214 TI - Factors that predict progression-free survival in Chinese lung adenocarcinoma patients treated with epidermal growth factor receptor tyrosine kinase inhibitors. AB - BACKGROUND: Although first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have shown efficacy in patients with advanced lung cancers, survival predictors with these drugs have not been extensively investigated. This study was performed to explore factors that may predict progression-free survival (PFS) in Chinese lung adenocarcinoma patients treated with EGFR-TKIs. METHODS: We retrospectively collected clinicopathologic data on 208 patients who received either gefitinib, erlotinib or icotinib, including the patients' EGFR mutation status and levels of six serum tumor markers [carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cancer antigen 125 (CA125), squamous cell carcinoma antigen (SCC), cytokeratin-19 fragments (CYFRA21-1) and lactate dehydrogenase (LDH)]. Univariate and multivariate survival analyses were performed to identify independent prognostic factors associated with PFS. RESULTS: At the study cutoff date, 189 (90.9%) of the patients met the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 criteria for progressive disease (PD), while 19 (9.1%) had stable disease (SD). The median PFS of the 208 patients was 12.4 months (95% CI, 11.0-13.8 months). In the multivariate analysis using a Cox proportional hazard model, a non-smoking history [hazard ratio (HR) =2.460; 95% CI, 1.484-4.079; P<0.001], first-line treatment (HR =1.500; 95% CI, 1.062-2.119; P=0.021), and a high pretreatment serum level of CEA (HR =1.424; 95% CI 1.026-1.977; P=0.035) were found to be significant predictors of a longer PFS. CONCLUSIONS: In Chinese lung adenocarcinoma patients treated with EGFR-TKIs, a non-smoking history, first-line EGFR-TKIs treatment and a high serum level of CEA were independent predictors of a longer PFS along with an EGFR-activating mutation. PMID- 26904215 TI - Clinicopathologic correlates of postoperative N1 or N2 nodal upstaging in non small cell lung cancer. AB - BACKGROUND: Clinical and pathologic determinations of lymph node staging are critical in the treatment of lung cancer. However, up- or downstaging of nodal status frequently is necessitated by postsurgical findings. This study was conducted to evaluate clinicopathologic features that impact nodal upstaging in patients staged primarily via positron emission tomography/computed tomography (PET/CT) and chest CT prior to surgery. METHODS: Between years 2011 and 2014, 634 patients underwent surgical treatment for non-small cell lung cancer (NSCLC) at our institution. Excluding 37 patients (given induction chemotherapy), 103 patients pathologically staged as N1 or N2 NSCLC. Nodal upstaging patients were classified into group A and non-upstaging patients into group B. We compared clinical characteristics and pathological results of group A with group B. RESULTS: Ultimately, 59 patients (57.3%) were assigned to group A and 44 patients (42.7%) to group B. Patients in group A (vs. group B) were significantly younger (61.6 vs. 68.4 years; P<0.001) and more often were female (47.5% vs. 15.9%; P=0.001), with shorter smoking histories (12.2 vs. 28.8 pack years; P<0.001) and lower maximum standardized uptake values (SUVmax) (7.3 vs. 10.4; P=0.001). Most upstaged (group A) tumors (50/59, 84.7%) were adenocarcinomas, displaying micropapillary (MPC; n=36) and lepidic (n=35) component positivity with significantly greater frequency (both, P<0.001); and the frequency of epidermal growth factor receptor (EGFR) mutation (n=36) was significantly greater in this subset (P=0.001). Multivariate analysis (logistic regression) indicated a significant correlation between MPC positivity and nodal upstaging (P=0.013). CONCLUSIONS: In patients upstaged postoperatively to N1 or N2 stage of NSCLC, occult lymph node metastasis and MPC positivity were significantly related. PMID- 26904216 TI - Predilection of contralateral upper lung metastasis in upper lobe lung adenocarcinoma patients. AB - BACKGROUND: Lung cancer with lung to lung metastasis is common. The objective of this study was to investigate the association among the distribution of contralateral lung metastases versus primary lung tumor location, clinical characteristics, and epidermal growth factor receptor (EGFR) mutations status. METHODS: The study included treatment-naive stage IV lung adenocarcinoma with contralateral lung metastases from 2012 through 2013. RESULTS: In total, 103 patients were enrolled after excluding lung cancer with histology other than adenocarcinoma, synchronous multiple primary lung cancers, or other active malignancy. The median age was 65 years (range, 28-93 years); 47 male patients (45.6%); 69 non-smoker (NS) patients (67.0%); 68 Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1 patients (66.0%); 38 M1a patients (38.9%); and 60 EGFR mutation patients (58.3%). There were 51 cases (49.5%) with primary lung cancer located over upper lobes. Among them, 36 (70.6%) had contralateral upper lung predominance metastasis, 9 (17.6%) had lower lung predominance, and 6 (11.8%) had equal distribution. Among the 52 lower lobe tumors, 17 (32.7%), 19 (36.5%), and 16 (30.8%) had upper, lower lung predominance, and equal distribution metastasis, respectively. Univariate analysis showed only male gender and primary tumor location over upper lobes were significantly associated with contralateral upper lung predominance metastases. After multivariate analysis, only primary tumor location over upper lobes was significantly associated with contralateral upper lung predominance metastases (adjusted OR 5.49, 95% CI, 2.15-14.03, P<0.001). CONCLUSIONS: Upper lobe lung adenocarcinoma was significantly associated with contralateral upper lung predominance metastases. Further research is needed to elucidate the mechanisms underlying this phenomenon. PMID- 26904217 TI - Air leakage on the postoperative day: powerful factor of postoperative recurrence after thoracoscopic bullectomy. AB - BACKGROUND: Primary spontaneous pneumothorax (PSP) is a relatively common disorder in young patients. Although various surgical techniques have been introduced, recurrence after video-assisted thoracoscopic surgery (VATS) remains high. The aim of study was to identify the risk factors for postoperative recurrence after thoracoscopic bullectomy in the spontaneous pneumothorax. METHODS: From January 2011 through March 2013, two hundreds and thirty two patients underwent surgery because of pneumothorax. Patients with a secondary pneumothorax, as well as cases of single port surgery, an open procedure, additional pleural procedure (pleurectomy, pleural abrasion) or lack of medical records were excluded. The records of 147 patients with PSP undergoing 3-port video-assisted thoracoscopic bullectomy with staple line coverage using an absorbable polyglycolic acid (PGA) sheet were retrospectively reviewed. RESULTS: The median age was 19 years (range, 11-34 years) with male predominance (87.8%). Median postoperative hospital stay was 3 days (range, 1-10 days) without mortality. Complications were developed in five patients. A total of 24 patients showed postoperative recurrence (16.3%). Younger age less than 17 years old and immediate postoperative air leakage were risk factors for postoperative recurrence after thoracoscopic bullectomy by multivariate analysis. CONCLUSIONS: Immediate postoperative air leakage was the risk factor for postoperative recurrence. However, further study will be required for the correlation of air leakage with recurrence. PMID- 26904218 TI - Targeted drugs for unselected patients with advanced non-small-cell lung cancer: a network meta-analysis. AB - BACKGROUND: Currently, targeted therapy has shown encouraging treatment benefits in selected patients with advanced non-small cell lung cancer (NSCLC). However, the comparative benefits of targeted drugs and chemotherapy (CT) treatments in unselected patients are not clear. We therefore conduct a network meta-analysis to assess the relative efficacy and safety of these regimens. METHODS: PubMed, EMBASE, Cochrane Library and abstracts from major scientific meetings were searched for eligible literatures. The odds ratio (OR) for objective response rate (ORR) and safety was used for pooling effect sizes. Bayesian network meta analysis was conducted to calculate the efficacy and safety of all included treatments. All tests of statistical significance were two sided. RESULTS: A total of 13,060 patients from 24 randomized controlled trials (RCT) were assessed. The targeted agents included bevacizumab (Bev), gefitinib (Gef), erlotinib (Erl) and cetuximab (Cet). Network meta-analysis showed that Bev + CT had a statistically significantly higher incidence of ORR relative to the other six different treatments, including placebo (OR =6.47; 95% CI, 3.85-10.29), Erl (OR =2.81; 95% CI, 2.08-3.70), CT (OR =1.92; 95% CI, 1.61-2.28), Gef (OR =1.40; 95% CI, 1.10-1.75), Erl + CT (OR =1.46; 95% CI, 1.17-1.80) and Gef + CT (OR =1.75; 95% CI, 1.36-2.22), whereas placebo and Erl were associated with statistically significantly lower incidence of ORR. Trend analyses of rank probability revealed that Bev + CT had the highest probability of being the best treatment arm in term of ORR, followed by Cet + CT. Meanwhile, Cet + CT showed significant severer rash and thrombocytopenia compared with Bev + CT. Gef was probable to be the rank 3 for ORR but was associated with relatively low risk for grade >=3 toxicities. CONCLUSIONS: Our study suggested that Bev + CT may offer better ORR in the treatment of unselected patients with advanced NSCLC. Future studies will be needed to investigate whether the increase of ORR with targeted drugs would be translated into survival benefits. PMID- 26904219 TI - Chemotherapy for patients with advanced lung cancer receiving long-term oxygen therapy. AB - BACKGROUND: Long-term oxygen therapy (LTOT) is sometimes prescribed for patients with advanced lung cancer who are potential candidates for chemotherapy. The aim of this study was to assess the usefulness of chemotherapy for patients with this disease who require LTOT. METHODS: The medical records of 40 patients with advanced lung cancer who received LTOT while undergoing systemic chemotherapy at our institution between January 2009 and December 2014 were retrospectively reviewed. Chemotherapy consisted of cytotoxic or molecular-targeted agents. RESULTS: Twenty-four patients had adenocarcinoma, 6 had squamous cell carcinoma, and 10 had small cell lung cancer (SCLC). The median survival time from the date of the first chemotherapy cycle performed in conjunction with LTOT was 194 days. In a multivariate analysis, the only factor significantly associated with better prognosis was the line (first or second) of the first chemotherapy with LTOT (hazard ratio =0.42; 95% confidence interval, 0.18 to 0.94). Among the 40 patients, 10 (25%) received chemotherapy during the last 30 days of their lives, 2 of whom died of chemotherapy-related adverse events. CONCLUSIONS: Chemotherapy for patients with advanced lung cancer who receive LTOT may be acceptable if it is the first- or second-line treatment. However, we should be mindful of the potential overuse of chemotherapy and its negative impact on quality of life. PMID- 26904220 TI - Left- and right-sided video-assisted thoracoscopic thymectomy exhibit similar effects on myasthenia gravis. AB - BACKGROUND: Unilateral video-assisted thoracoscopic (VATS) thymectomy features less operative trauma, improved cosmesis, and similar efficiency compared with transsternal (TS) thymectomy for treatment of patients with myasthenia gravis (MG). Unilateral VATS thymectomy can be easily performed from either side of the thorax, because thymus is located in the middle of mediastinum. Nevertheless, the side that provides better outcomes remains controversial. This study presents our experience on treatments for MG and reveals the differences between the unilateral VATS thymectomy performed on each side. METHODS: Eighty-one consecutive patients with MG who underwent TS or VATS thymectomy on either side between January 2003 and December 2012 were enrolled in the study. Clinicopathologic data and surgical outcomes were retrospectively analyzed and compared among different surgical approaches. RESULTS: TS thymectomy was administered in 50 patients, whereas unilateral VATS approaches were performed on the remaining 31 patients, 15 on the left side and 16 on the right side. The VATS group exhibited a significantly shorter surgery duration (P<0.001), less intraoperative blood loss (P=0.009), shorter postoperative hospital stay (P=0.025), smaller thoracic drainage volume (P=0.033), shorter thoracic drainage duration (P=0.006), and less postoperative complications (P<0.001) compared with the TS group. However, disease remission rates did not significantly differ among the groups (P=0.988). The left-sided group exhibited considerably longer thoracic drainage duration than the right-sided group (P=0.041). Moreover, surgical time (P=0.736), intraoperative blood loss (P=0.281), postoperative hospital stay (P=0.599), thoracic drainage volume (P=0.571), postoperative complications (P=0.742) and therapeutic effect (P=1.000) did not significantly differ among the groups. Multivariate analysis revealed that the ocular type of MG is the only independent factor for clinical remission (P=0.002). CONCLUSIONS: Unilateral VATS thymectomy can reduce surgical risks and shorten hospitalization duration without threatening the therapeutic effect. This technique can be safely and effectively performed by experienced surgeons in either side of the thorax. PMID- 26904221 TI - Reoperations after tricuspid valve repair: re-repair versus replacement. AB - BACKGROUND: Data demonstrating results of reoperation after initial tricuspid valve repair are scarce. We evaluated outcomes of tricuspid reoperations after tricuspid valve repair and compared the results of tricuspid re-repair with those of tricuspid valve replacement (TVR). METHODS: From 1994 to 2012, 53 patients (56+/-15 years, male:female =14:39) underwent tricuspid reoperations due to recurrent tricuspid regurgitation (TR) after initial repair. Twenty-two patients underwent tricuspid re-repair (TAP group) and 31 patients underwent TVR (TVR group). RESULTS: Early mortality occurred in 6 patients (11%). Early mortality and incidence of postoperative complications were similar between the 2 groups. There were 14 cases of late mortality including 9 cardiac deaths. Five- and 10 year free from cardiac death rates were 82% and 67%, respectively, without any intergroup difference. Recurrent TR (> moderate) developed in 6 TAP group patients and structural valve deterioration occurred in 1 TVR group patient (P=0.002). Isolated tricuspid valve surgery (P=0.044) and presence of atrial fibrillation during the follow-up (P=0.051) were associated with recurrent TR after re-repair. However, the overall tricuspid valve-related event rates were similar between the 2 groups with 5- and 10-year rates of 61% and 41%, respectively. CONCLUSIONS: Tricuspid valve reoperation after initial repair resulted in high rates of operative mortality and complications. Long-term event free rate was similar regardless of the type of surgery. However, great care might be needed when performing re-repair in patients with atrial fibrillation and those who had isolated tricuspid valve disease due to high recurrence of TR after re-repair. PMID- 26904222 TI - Selection for adjuvant chemotherapy in completely resected stage I non-small cell lung cancer: external validation of a Chinese prognostic risk model. AB - BACKGROUND: The ability to sub-stratify survival within stage I is an important consideration as it is assumed that survival is heterogeneous within this sub group. Liang et al. recently published a nomogram to predict post-operative survival in patients undergoing lung cancer surgery. The aim of our study is external validation of their published nomogram in a British cohort focusing on stages IA and IB to determine applicability in selection of adjuvant chemotherapy within stage I. METHODS: Patient variables were extracted and the score individually calculated. Receiver operative characteristics curve (ROC) was calculated and compared with the original derivation cohort and the discriminatory ability was further quantified using survival plots by splitting our (external) validation cohort into three tertiles and Kaplan Meier plots were constructed and individual curves tested using Cox regression analysis on Stata 13 and R 3.1.2 respectively. RESULTS: A total of 1,238 patients were included for analysis. For all patients from stage IA to IIB the mean (SD) score was 9.95 (4.2). The ROC score comparing patients who died versus those that remained alive was 0.62 (95% CI: 0.58 to 0.67). When divided into prognostic score tertiles, survival discrimination remained evident for the entire cohort, as well as those for stage IA and IB alone. The P value comparing survival between the middle and highest score with baseline (low score) was P=0.031 and P=0.034 respectively. CONCLUSIONS: Our results of external validation suggested lower survival discrimination than reported by the original group; however discrimination between survival remained evident for stage I. PMID- 26904223 TI - Comparison of clinical features and polysomnographic findings between men and women with sleep apnea. AB - BACKGROUND: There is a scarcity of reports comparing gender differences in polysomnographic findings among Asian patients with sleep apnea (SA). In this study, we elucidated gender differences in the clinical features and polysomnographic findings of SA patients in Japan. METHODS: We conducted a case matched control study to compare the gender differences. A total of 4,714 patients (4,127 men; 587 women) were matched for age, apnea-hypopnea index (AHI), and body mass index (BMI). The criteria used for sex matching were (I) age +/-4 years, (II) AHI +/- 4 h of sleep, and (III) BMI +/-2 kg/m(2). This facilitated the comparison of polysomnography sleep variables in 296 men and 296 women with SA. RESULTS: Compared with their male counterparts, female SA patients had a significantly higher rapid eye movement AHI [men: 27.7 (IQR, 14.3-45.2); women: 43.3 (IQR, 25.5-56.6); P<0.001], lower supine AHI [men: 29.7 (IQR, 16.8-49.5); women: 25.0 (IQR, 14.7-39.3); P=0.004], longer total sleep time (TST), and non rapid eye movement (NREM) sleep stage 3 (N3), %TST [TST in men: 356.3 (IQR, 319.5 392.3); women: 372.0 (IQR, 327.8-404.5); P=0.007; N3, %TST in men: 8.8 (IQR, 3.0 14.6); women: 14.4 (IQR, 8.3-20.4); P<0.001], and better sleep efficiency [men: 80.9 (IQR, 71.0-88.0); women: 83.2 (IQR, 74.5-90.0); P=0.011]. CONCLUSIONS: This study revealed that women with SA had a significantly longer TST and N3, %TST, which represents deep sleep. Future prospective studies must be conducted together with polysomnography tests including electromyography of pharyngeal muscle expansion and electroencephalography. PMID- 26904224 TI - Prediction and prognostic factors of post-recurrence survival in recurred patients with early-stage NSCLC who underwent complete resection. AB - BACKGROUND: This study aimed to evaluate prognostic factors of post-recurrence survival (PRS) and to improve survival in recurred patients with early-stage non small cell lung cancer (NSCLC). METHODS: The 141 patients with recurrence after complete resection of stage I and II NSCLC between 1995 and 2012 was retrospectively reviewed. Overall PRS and PRS of the patient groups stratified according to the sum of their own risk scores were analyzed. RESULTS: The patterns of recurrence of 141 patients included local only in 40(28.4%), distant only in 86 (61%) and both in 15 (10.6%) patients. Of 141 patients, 110 patients received post-recurrence therapy. The overall 1- and 3-year PRS rates were 50.7% and 28.4%, respectively. Extensive pulmonary resection (P=0.001), poor histologic differentiation (P=0.009), symptom at initial recurrence (P=0.000), no pulmonary metastasis (P=0.006), no post-recurrence therapy (P=0.001) were significant risk factors in univariate analysis. Multivariate analysis revealed that extent of pulmonary resection [hazard ratio (HR), 2.039; 95% confidence interval (CI), 1.281 to 3.244; P=0.003; risk score 1.0], histologic differentiation HR, 3.125; 95% CI, 1.976 to 4.941; P=0.000; risk score 1.5), symptom (HR, 3.154; 95% CI, 2.000 to 4.972; P=0.000; risk score 1.5) and post-recurrence therapy (HR, 2.330; 95% CI, 1.393 to 3.899; P=0.001; risk score 1.1) were significant prognostic factors. The recurred patients whose risk score sums were 1.1 or less were assigned to Group I; between 1.5 and 2.1, to Group II; and more than 2.5, to Group III. Significant differences in their PRS rates were confirmed (P=0.000). CONCLUSIONS: Extent of pulmonary resection, histologic differentiation, symptom and post-recurrence therapy are a prognostic factor for PRS. Based on the hazard ratios of each factors, the risk scores were yielded. And the recurred patients were stratified according to the sum of their risk scores based on their PRS rates. Therefore, these results may help advancements in making predictions for their prognosis and the improvement of PRS. PMID- 26904225 TI - Long-term respiratory function recovery in patients with stage I lung cancer receiving video-assisted thoracic surgery versus thoracotomy. AB - BACKGROUND: Video-assisted thoracic surgery (VATS) and thoracotomy are standard treatment methods for early lung cancer. We compared their effects on the long term recovery of pulmonary function in patients with stage I non-small cell lung cancer (NSCLC). METHODS: We retrospectively reviewed 203 patients with early NSCLC who underwent VATS or thoracotomy at Seoul University Hospital from January 2005 to December 2010. Two matched groups (VATS and thoracotomy) each consisting of 60 patients were created via propensity score matching according to TNM stage, age, sex, smoking history, lung disease history, and preoperative pulmonary function. RESULTS: There were no significant differences in the recovery of forced expiratory volume in 1 second, the forced vital capacity (FVC), or the peak flow rate (PFR), presented as the postoperative value/predicted value, between the VATS and thoracotomy groups during the 12-month follow-up period. The standardized functional loss ratio [(measured postoperative value - predicted postoperative value)/(predicted postoperative value * 100)] did not differ between the two groups at 6 and 12 months. In an intragroup analysis, the postoperative FVC in the thoracotomy group remained below predicted postoperative value during the follow-up period and did not reach the predicted postoperative FVC (6 months/12 months: -6.58%/-2.43%). The analgesic requirements and pain procedures were similar in the VATS and thoracotomy groups during the 12-month follow-up period. CONCLUSIONS: There were no significant differences in pulmonary function recovery during the late postoperative period in NSCLC patients receiving VATS versus thoracotomy. We suggest that the volume of the resected lung and preoperative lung function are the main determinants of late recovery, rather than postoperative pain. PMID- 26904226 TI - Differing histopathology and prognosis in pulmonary adenocarcinoma at central and peripheral locations. AB - BACKGROUND: Pulmonary adenocarcinoma is largely peripheral in location but often does occur centrally. In the course of this study, clinicopathologic features of pulmonary adenocarcinoma, including the prognosis of early-stage disease, were assessed and compared by tumor location. METHODS: A retrospective chart review was conducted, examining 308 patients treated for pulmonary adenocarcinoma by curative resection. Clinicopathologic findings were analyzed, comparing central and peripheral primary locations. Recurrence-free survival (RFS) rates were determined for tumor subsets (central vs. peripheral). RESULTS: At all disease stages (N=308), 41 patients (13.3%) with central adenocarcinoma were documented. In central (vs. peripheral) adenocarcinoma, mean tumor size was larger (3.1 vs. 2.3 cm, P=0.014), nodal metastasis was more frequent (P=0.012), and the likelihood of advanced disease (stages II and III) was greater (P=0.007). Microscopically, central adenocarcinoma displayed more acinar (53.3% vs. 38.9%; P=0.006) and less lepidic (20.9% vs. 37.5%; P=0.001) growth. At stage I disease [N=329; central, 25 (10.5%)], group similarities were sustained. As with disease overall, central adenocarcinoma contained more acinar (51.8% vs. 37.1%; P=0.025) and fewer lepidic (26.2% vs. 44.1%; P=0.006) areas. Three-year RFS rates for central and peripheral adenocarcinoma at all disease stages were 63.2% and 82.5% (P=0.024), respectively, compared with 70.4% and 91.0% (P=0.023), respectively at stage I. Lepidic growth was identified as a statistically significant risk factor for early recurrence by multivariate analysis. CONCLUSIONS: Central pulmonary adenocarcinoma is generally detected at an advanced stage. In early (stage I) disease, the prognosis is comparatively worse for central adenocarcinoma, owing to significant micromorphologic differences in central and peripheral tumors. PMID- 26904227 TI - A stepwise protocol for the treatment of refractory gastroesophageal reflux induced chronic cough. AB - BACKGROUND: Refractory gastroesophageal reflux-induced chronic cough (GERC) is difficult to manage. The purpose of the study is to evaluate the efficacy of a novel stepwise protocol for treating this condition. METHODS: A total of 103 consecutive patients with suspected refractory reflux-induced chronic cough failing to a standard anti-reflux therapy were treated with a stepwise therapy. Treatment commences with high-dose omeprazole and, if necessary, is escalated to subsequent sequential treatment with ranitidine and finally baclofen. The primary end-point was overall cough resolution, and the secondary end-point was cough resolution after each treatment step. RESULTS: High-dose omeprazole eliminated or improved cough in 28.1% of patients (n=29). Further stepwise of treatment with the addition of ranitide yielded a favorable response in an additional 12.6% (n=13) of patients, and subsequent escalation to baclofen provoked response in another 36.9% (n=38) of patients. Overall, this stepwise protocol was successful in 77.6% (n=80) of patients. The diurnal cough symptom score fell from 3 [1] to 1 [0] (Z=6.316, P=0.000), and the nocturnal cough symptom score decreased from 1 [1] to 0 [1] (Z=-4.511, P=0.000), with a corresponding reduction in the Gastroesophageal Reflux Diagnostic Questionnaire score from 8.6+/-1.7 to 6.8+/ 0.7 (t=3.612, P=0.000). Conversely, the cough threshold C2 to capsaicin was increased from 0.49 (0.49) umol/L to 1.95 (2.92) umol/L (Z=-5.892, P=0.000), and the cough threshold C5 was increased from 1.95 (2.92) umol/L to 7.8 (5.85) umol/L (Z=-5.171, P=0.000). CONCLUSIONS: Sequential stepwise anti-reflux therapy is a useful therapeutic strategy for refractory reflux-induced chronic cough. PMID- 26904228 TI - Electromagnetic navigation transthoracic needle aspiration for the diagnosis of pulmonary nodules: a safety and feasibility pilot study. AB - BACKGROUND: Pulmonary nodules remain a diagnostic challenge for physicians. Minimally invasive biopsy methods include bronchoscopy and CT guided transthoracic needle aspiration (TTNA). A novel electromagnetic guidance transthoracic needle aspiration (ETTNA) procedure which can be combined with navigational bronchoscopy (NB) and endobronchial ultrasound (EBUS) in a single setting has become available. METHODS: A prospective pilot study examining the safety, feasibility and diagnostic yield of ETTNA in a single procedural setting. All patients enrolled underwent EBUS for lung cancer staging followed by NB and ETTNA. Feasibility of performing ETTNA and a safety assessment by recording procedural related complications including pneumothorax or bleeding was performed. Diagnostic yield of ETTNA defined by a definitive pathologic tissue diagnosis was recorded. An additional diagnostic yield analysis was performed using a cohort analysis of combined interventions (EBUS + NB + ETTNA). All non diagnostic biopsies were either followed with radiographic imaging or a surgical biopsy was performed. RESULTS: Twenty-four subjects were enrolled. ETTNA was feasible in 96% of cases. No bleeding events occurred. There were five pneumothoraces (21%) of which only two (8%) subjects required drainage. The diagnostic yield for ETTNA alone was 83% and increased to 87% (P=0.0016) when ETTNA was combined with NB. When ETTNA and NB were performed with EBUS for complete staging, the diagnostic yield increased further to 92% (P=0.0001). CONCLUSIONS: This is the first human pilot study demonstrating an acceptable safety and feasibility profile with a novel ETTNA system. Further studies are needed to investigate the increased diagnostic yield from this pilot study. PMID- 26904229 TI - Contemporary role of minimally invasive thoracic surgery in the management of pulmonary arteriovenous malformations: report of two cases and review of the literature. AB - Pulmonary arteriovenous malformations (PAVM) can have potentially serious neurological and cardiac consequences if left untreated. Embolization has supplanted surgical resection as the first line treatment modality. However, this technique is not always successful and carries risks of air embolism, migration of the coil, myocardial rupture, vascular injury, pulmonary hypertension, and pulmonary infarction. We present two patients with symptomatic PAVM despite multiple embolizations: the first one with recurrent and persistent hemoptysis who underwent a thoracoscopic lobectomy, and the second one with chronic debilitating pleuritic pain subsequent to embolization who underwent a thoracoscopic wedge resection. Video-assisted thoracoscopic surgery (VATS) with lung resection was successfully performed in both patients, with complete resolution of their symptoms. We also review the literature regarding the contemporary role of surgery in PAVM, particularly thoracoscopy. PMID- 26904230 TI - Video-assisted thoracoscopic surgery tracheal resection and carinal reconstruction for tracheal adenoid cystic carcinoma. AB - We report a case of video-assisted thoracoscopic surgery (VATS) tracheal resection and carinal reconstruction in a patient with tracheal tumor. The patient presented with adenoid cystic carcinoma (ACC) of the distal trachea, extending along the right main bronchus with carinal invasion. The reconstruction procedure was assisted with cross-field ventilation. Postoperative clinical course of this case was good. The forced expiratory volume in the first second (FEV1) improved from 0.461 L (17% pred.) to 2.31 L (87% pred.) 1 month after the operation. VATS tracheal resection and carinal reconstruction is a feasible option for patients with tracheal tumor with carina involvement. PMID- 26904231 TI - Thoracoscopic and laparoscopic radical esophagectomy with left neck anastomosis. AB - We described a 50-year-old female, who came to our institute with the diagnosis of esophageal squamous cell carcinoma. The preoperative clinical diagnosis was stage II esophageal squamous cell carcinoma. The minimally invasive esophagectomy (MIE), combined thoracoscopic-laparoscopic esophagectomy with cervical anastomosis, was performed in this case. Total surgery time was 190 min and blood loss was 100 mL. Postoperative pathological exam suggested squamous cell carcinoma, without evidence of lymph node metastasis in any station (T2N0M0 IIb stage). The patient was discharged home on the 12(th) postoperative day. PMID- 26904232 TI - Approaches to prevent the patients with chronic airway diseases from exacerbation in the haze weather. AB - Haze weather is becoming one of the biggest problems in many big cities in China. It triggers both public anxiety and official concerns. Particulate matter (PM) plays the most important role in causing the adverse health effects. Chemical composition of PM2.5 includes primary particles and secondary particles. The toxicological mechanisms of PM2.5 to the human body include the oxidative stress, inflammation and carcinogenesis. Short or long-term exposure to PM (especially PM2.5) can cause a series of symptoms including respiratory symptoms such as cough, wheezing and dyspnea as well as other symptoms. There are positive associations between PM2.5 and mortality due to a number of causes. PM2.5 is considered to contribute to the onset of asthma, the exacerbation of chronic obstructive pulmonary disease (COPD) in haze weather. Some approaches including outdoor health care, indoor health care and preventive medications can prevent the patients with chronic airway diseases from exacerbations. PMID- 26904233 TI - New puzzles for the use of non-invasive ventilation for immunosuppressed patients. AB - On October 27, 2015, Lemile and colleagues published an article in JAMA entitled "Effect of Noninvasive Ventilation vs. Oxygen Therapy on Mortality among Immunocompromised Patients with Acute Respiratory Failure: A Randomized Clinical Trial", which investigated the effects of non-invasive ventilation (NIV) in 28 day mortality of 374 critically ill immunosuppressed patients. The authors found that among immunosuppressed patients admitted to the intensive care unit (ICU) with hypoxemic acute respiratory failure, early NIV compared with oxygen therapy alone did not reduce 28-day mortality. Furthermore, different from the previous publications, there were no significant differences in ICU-acquired infections, duration of mechanical ventilation, or lengths of ICU or hospital stays. The study power was limited, median oxygen flow used was higher than used before or 9 L/min, NIV settings provided tidal volumes higher than what is considered protective nowadays or from 7 to 10 mL/kg of ideal body weight and the hypoxemic respiratory failure was moderate to severe (median PaO2/FIO2 was around 140), a group prone to failure in noninvasive ventilatory support. Doubts arose regarding the early use of NIV in immunosuppressed critically ill patients with non hypercapnic hypoxemic respiratory failure that need to be solved in the near future. PMID- 26904234 TI - Use of intravascular ultrasound vs. optical coherence tomography for mechanism and patterns of in-stent restenosis among bare metal stents and drug eluting stents. AB - This article is a perspective responses to the "Mechanisms and Patterns of Intravascular Ultrasound In-Stent Restenosis Among Bare Metal Stents and First- and Second-Generation Drug-Eluting Stents" by Goto et al., The above mentioned article outlines the use of intravascular ultrasound (IVUS) in visualizing the patterns and mechanisms of in-stent restenosis (ISR) post percutaneous coronary intervention (PCI). Although IVUS is an appropriate method of choice for this scenario, IVUS has certain limitations which can be overcome by using optical coherent tomography (OCT). OCT is not only able to overcome IVUS's limitations but is also able to provide additional information to enhance the understanding of in-stent restenotic lesions. This article also outlines the future directions for OCT both in clinical and investigation settings. PMID- 26904235 TI - Acetaminophen in critically ill patients, a therapy in search for big data analytics. PMID- 26904236 TI - Acetaminophen for febrile patients with suspected infection: potential benefit and further directions. PMID- 26904237 TI - When clinical experiences clashes against evidence based medicine: the case of aspiration thrombectomy in primary percutaneous coronary intervention (PCI). PMID- 26904238 TI - Continuous or interrupted chest compressions for EMS-performed cardiopulmonary resuscitation. PMID- 26904239 TI - To interrupt, or not to interrupt chest compressions for ventilation: that is the question! PMID- 26904240 TI - Adult patient with pulmonary agenesis: focusing on one-lung ventilation during general anesthesia. AB - Congenital pulmonary agenesis is a rare condition with high mortality. Mechanical ventilation in these patients is challenging and there has no such case been reported in the literature. We reported a 61-year-old female with lung agenesis who presented to our hospital with pneumonia and pelvic mass. In the past, she had undergone repairing of atrial septal defect and mitral valve forming surgery at 6-year-old. Thereafter she had remained asymptomatic until this time of hospital admission. The patient underwent operation for the pelvic mass with one lung ventilation (OLV) under general anesthesia. We highlighted the use of protective ventilation (PV) strategy during OLV. PMID- 26904241 TI - Recurrent infarctions due to a dome-shaped pannus above the mitral valve prosthesis. AB - This report describes a unique case of a 56-year-old female who suffered from recurrent stroke after double mechanical valve replacement. During the four years after the surgery, she remained in normal sinus rhythm, received adequate anticoagulation therapy, and no apparent left atrial thrombus was detected. She underwent redo surgery to prevent further stroke after fourth instance of cerebral infarction. Intraoperative findings revealed a 'dome-shaped' pannus formation covering the sewing ring of the mitral prosthesis circumferentially, probably leading to clot formation and repeated infarctions. She has been stroke free for three years after pannus resection. PMID- 26904242 TI - A primary malignant melanoma of the mediastinum with gross surgical view. AB - Primary malignant mediastinal melanomas are rare. Few studies have reported on the chest computed tomography (CT) scan and histopathological features. We report a case of a primary malignant mediastinal melanoma in a 32-year-old man and provide a gross surgical view of the tumour. PMID- 26904243 TI - A successful percutaneous mechanical vegetation debulking used as a bridge to surgery in acute tricuspid valve endocarditis. AB - Timing of surgical management of acute infective endocarditis is a major challenge, with respect to surgical complications, risks of recurrences and optimal valve repair or replacement. We present a case of a 24-year-old male with a history of intravenous drug abuse, who was referred to our center after 10 days of medical management of acute infective endocarditis. Upon arrival he was in septic shock, multi-organ failure, and mobile vegetations on the tricuspid valve with severe tricuspid regurgitation. He also had bilateral pulmonary infarcts and an ischemic stroke in the right parietal lobe. A successful percutaneous transcatheter mechanical vegetation debulking was performed followed by surgical valve replacement seven days later. This case introduces a new option in the management of right-sided endocarditis in critically ill patient, and demonstrates the technical feasibility of a debulking procedure in this setting, which led subsequently to a significant improvement in patient's condition, and he was ultimately able to undergo definitive surgery. PMID- 26904244 TI - Management of long-term persistent air leakage developed after bullectomy for giant bullous lung disease associated with neurofibromatosis type 1. AB - Persistent air leakage is a serious and sometimes fatal complication of bullous lung disease surgery. A 32-year-old man with lung involvement of neurofibromatosis type I underwent bullectomy for huge bullae and recurrent pneumothorax. Persistent postoperative air leakage developed and the lung was totally collapsed. The initial surgery failed, but a second trial employing a novel suture technique on half-absorbed polyglycolic acid (PGA) felt successfully resolved the massive air leakage. Pneumothorax did not recur and the patient remained stable without dyspnea. Thus, a suture technique employing half-absorbed PGA felt was an effective option for managing persistent air leakage. PMID- 26904245 TI - Saline prosthesis implantation using an extrapleural approach for the treatment of postpneumonectomy-like syndrome due to tuberculosis-destroyed lung. AB - Postpneumonectomy-like syndrome is very rare disease caused by parenchymal lung disease. Here we present a case of surgical management of postpneumonectomy-like syndrome occurred by tuberculosis destroyed lung. A 43-year-old women with tuberculosis destroyed lung presented with dyspnea. She underwent surgery for extra-pleura dissection and implant a normal saline breast bag to reposition mediastinum. The patient is alive with stable pulmonary function. PMID- 26904246 TI - Single-incision video-assisted thoracic surgery lobectomy in the treatment of adult communicating bronchopulmonary foregut malformation with large aberrant artery. AB - Single-incision thoracoscopic surgery (SITS) is not yet widely used for treating pulmonary sequestration due to the difficulty of manipulating an aberrant systemic artery or working around inflamed tissue. It is also difficult to control massive bleeding if the aberrant artery ruptures during excision. We modified the SITS lobectomy technique so that it was suitable for treating pulmonary sequestration. We changed the order of excision of anatomical structures and introduced two-stage stapling of the aberrant artery for easy, safe stapling in SITS lobectomy. Single-port VATS is an acceptable method for major pulmonary resection for the treatment of intrapulmonary sequestration. PMID- 26904247 TI - Efficacy and safety of human fibrinogen-thrombin patch (Tachosil((r))) in the management of diffuse bleeding after chest wall and spinal surgical resection for aggressive thoracic neoplasms. AB - Diffuse bleeding after chest wall and spine resection represents a major problem in General Thoracic Surgery. Several fibrin sealants (FS) have been developed over the years and their use has been gradually increasing over time, becoming an important aid to the surgeons, justifying their use across numerous fields of surgery due to its valid haemostatic properties. Among the several FS available, TachoSil((r)) (Takeda Austria GmbH, Linz, Austria) stands out for its haemostatic and aerostatic properties, the latter being demonstrated even in high-risk patients after pulmonary resections for primary lung cancers. Several papers available in literature demonstrated TachoSil((r))'s effectiveness in controlling intraoperative and postoperative bleeding in different surgical branches, including hepatic and pancreatic surgery, as well as cardiac and thoracic surgery. However, the use of TachoSil((r)) to control diffuse bleeding following major resections for advanced lung cancers, with requirement of chest wall and vertebral body resection for oncological radicality, was never published so far. In this paper, we report three cases of pulmonary lobectomy associated to chest wall resection and haemivertebrectomy for primary malignant lung neoplasms and for a recurrence of malignant solitary fibrous tumour of the pleura in which we used TachoSil((c)), which demonstrated its efficacy in controlling diffuse bleeding following resection. PMID- 26904248 TI - Asymptomatic localized pleural amyloidosis mimicking malignant pleural mesothelioma: report of a case. AB - We herein report an asymptomatic 65-year-old male with localized pleural amyloidosis mimicking malignant pleural mesothelioma. He had a history of exposure to asbestos and was admitted for investigation of an abnormal pleural thickness detected by chest radiography. Positron emission tomography showed elevation of standardized uptake value corresponding to the pleural thickness. Partial pleurectomy including the tumor was performed for the purpose of diagnosis and local disease control. The pathological examination showed that the tumor was pleural amyloidosis. The tumor was diagnosed as localized primary amyloidosis, because serum monoclonal protein concentration did not increase. Pleural amyloidosis should be considered as a differential diagnosis from pleural mesothelioma. PMID- 26904249 TI - Erratum to clinical role of a new prognostic score using platelet-to-lymphocyte ratio in patients with malignant pleural mesothelioma undergoing extrapleural pneumonectomy. AB - [This corrects the article on p. 1898 in vol. 7, PMID: 26716028.]. PMID- 26904250 TI - Pollutional haze and COPD: etiology, epidemiology, pathogenesis, pathology, biological markers and therapy. AB - In recent years, serious pollutional haze occurs in the mainland of China thanks to the development of urbanization and industrialization. There is a close relationship between air pollution and the occurrence and development of chronic obstructive pulmonary disease (COPD), but there are some new characteristics in some aspects of COPD associated with pollutional haze compared with COPD induced by traditional physical and chemical factors. This article attempts to summarize the new progress from these new features of COPD related to pollutional haze, focus on etiology, epidemiology, pathogenesis, pathology, biological markers and therapy. PMID- 26904251 TI - Air pollution and chronic airway diseases: what should people know and do? AB - The health effects of air pollution remain a public health concern worldwide. Exposure to air pollution has many substantial adverse effects on human health. Globally, seven million deaths were attributable to the joint effects of household and ambient air pollution. Subjects with chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma are especially vulnerable to the detrimental effects of air pollutants. Air pollution can induce the acute exacerbation of COPD and onset of asthma, increase the respiratory morbidity and mortality. The health effects of air pollution depend on the components and sources of pollutants, which varied with countries, seasons, and times. Combustion of solid fuels is a major source of air pollutants in developing countries. To reduce the detrimental effects of air pollution, people especially those with COPD or asthma should be aware of the air quality and take extra measures such as reducing the time outdoor and wearing masks when necessary. For reducing the air pollutants indoor, people should use clean fuels and improve the stoves so as to burn fuel more efficiently and vent emissions to the outside. Air cleaners that can improve the air quality efficiently are recommended. PMID- 26904252 TI - The effect of pollutional haze on pulmonary function. AB - Detrimental health effects of atmospheric exposure to ambient particulate matter (PM) have been investigated in numerous studies. Exposure to pollutional haze, the carrier of air pollutants such as PM and nitrogen dioxide (NO2) has been linked to lung and cardiovascular disease, resulting increases in both hospital admissions and mortality. This review focuses on the constituents of pollutional haze and its effects on pulmonary function. The article presents the available information and seeks to correlate pollutional haze and pulmonary function. PMID- 26904253 TI - Progress in the impact of polluted meteorological conditions on the incidence of asthma. AB - It has been revealed by many studies that air pollution is one of the important inducements of asthma exacerbations. In addition, meteorological conditions such as high atmospheric pressure, low temperature, low humidity and large diurnal amplitude can directly induce asthma. Meanwhile, meteorological conditions play an important role in the diffusion, dilution and accumulation of air pollution. This article reviewed research progress in the impact of polluted meteorological conditions on the incidence of asthma. PMID- 26904254 TI - Interventions to reduce individual exposure of elderly individuals and children to haze: a review. AB - Given rapid economic developments and urbanization over the last few decades, China has experienced frequent haze episodes, which have adverse effects on public health. Children and elderly individuals are more susceptible than the general population to air pollution. In this study, we introduce interventions to reduce the exposure of elderly individuals and children to air pollution during hazy weather. These interventions include avoiding outdoor activities, wearing a dust mask, reducing burning biomass fuels, reducing frying and smoking at home, using an air filtration unit and taking supplemental antioxidants. However, the actual benefits of these measures remain unproven and are unlikely to be adequate. Sustained clean air policies remain the most important and efficient solution to reduce air pollution-related health effects. PMID- 26904255 TI - The impact of PM2.5 on the human respiratory system. AB - Recently, many researchers paid more attentions to the association between air pollution and respiratory system disease. In the past few years, levels of smog have increased throughout China resulting in the deterioration of air quality, raising worldwide concerns. PM2.5 (particles less than 2.5 micrometers in diameter) can penetrate deeply into the lung, irritate and corrode the alveolar wall, and consequently impair lung function. Hence it is important to investigate the impact of PM2.5 on the respiratory system and then to help China combat the current air pollution problems. In this review, we will discuss PM2.5 damage on human respiratory system from epidemiological, experimental and mechanism studies. At last, we recommend to the population to limit exposure to air pollution and call to the authorities to create an index of pollution related to health. PMID- 26904256 TI - Daily lifestyles in the fog and haze weather. AB - BACKGROUND: China is being plagued by a large-scaled lasting fog and haze, under which people have to work and live. Therefore, it matters to do what we can to minimize the adverse impact of the fog and haze on individual health on a daily basis. METHODS: Relative literatures on the fog and haze have been searched and reviewed. Particular attention has been paid to the literatures on the adverse impact of the fog and haze on the people's health and on the ways minimizing this impact. RESULTS: Coming across the weather of fog and haze, appropriate measures taken can minimize its adverse impact on individuals on a daily basis. The measures included vitamin intake, water drinking, air cleaning indoors, stay-at home, and mask wearing outdoors. These measures are simple and proven effective. CONCLUSIONS: Simple and effective measures seem to be sufficient to minimizing the adverse impact of the fog and haze on the individual's health on a daily basis. Lifestyle changes, awareness of environment protection, energy conservation, and new and clean energy use are ultimate ways to curb the air pollution and reduce the occurrence of the fog and haze. PMID- 26904257 TI - Surgical treatment of air way disease. AB - Airway lesions are treated by resecting and subsequent reconstructive surgery. Tracheoplasty and bronchoplasty are applied to inflammatory stenosis, damage due to trauma, and primary tumors of the airways. The indications for lobar (bronchial) sleeve resection are commonly applied to lung cancers that develop at the proximal portion of the lobar bronchus. Recently, extended sleeve lobectomy (ESL) is widely indicated among the routine techniques used to avoid pneumonectomy because of its reliability and effectiveness. In some cases the cancer is limited to the segmental bronchi, segmental sleeve resection is sometimes performed. In the field of respiratory surgery, carinal resection reconstruction is one of the most rare procedures and challenging issues, involving difficult surgical techniques, anesthetic techniques, and postoperative management. Tracheal surgery was generalized so that it could be applied to any type of tracheal disease that required resection, including tumors. PMID- 26904259 TI - Transcatheter valve-in-valve implantation versus reoperative conventional aortic valve replacement: a systematic review. AB - Transcatheter valve-in-valve (VIV) implantation for degenerated aortic bioprostheses has emerged as a promising alternative to redo conventional aortic valve replacement (cAVR). However there are concerns surrounding the efficacy and safety of VIV. This systematic review aims to compare the outcomes and safety of transcatheter VIV implantation with redoes cAVR. Six databases were systematically searched. A total of 18 relevant studies (823 patients) were included. Pooled analysis demonstrated VIV achieved significant improvements in mean gradient (38 mmHg preoperatively to 15.2 mmHg postoperatively, P<0.001) and peak gradient (59.2 to 23.2 mmHg, P=0.0003). These improvements were similar to the outcomes achieved by cAVR. The incidence of moderate paravalvular leaks (PVL) were significantly higher for VIV compared to cAVR (3.3% vs. 0.4%, P=0.022). In terms of morbidity, VIV had a significantly lower incidence of stroke and bleeding compared to redo cAVR (1.9% vs. 8.8%, P=0.002 & 6.9% vs. 9.1%, P=0.014, respectively). Perioperative mortality rates were similar for VIV (7.9%) and redo cAVR (6.1%, P=0.35). In conclusion, transcatheter VIV implantation achieves similar haemodynamic outcomes, with lower risk of strokes and bleeding but higher PVL rates compared to redo cAVR. Future randomized studies and prospective registries are essential to compare the effectiveness of transcatheter VIV with cAVR, and clarify the rates of PVLs. PMID- 26904258 TI - Air particulate matter and cardiovascular disease: the epidemiological, biomedical and clinical evidence. AB - Air pollution is now becoming an independent risk factor for cardiovascular morbidity and mortality. Numerous epidemiological, biomedical and clinical studies indicate that ambient particulate matter (PM) in air pollution is strongly associated with increased cardiovascular disease such as myocardial infarction (MI), cardiac arrhythmias, ischemic stroke, vascular dysfunction, hypertension and atherosclerosis. The molecular mechanisms for PM-caused cardiovascular disease include directly toxicity to cardiovascular system or indirectly injury by inducing systemic inflammation and oxidative stress in peripheral circulation. Here, we review the linking between PM exposure and the occurrence of cardiovascular disease and discussed the possible underlying mechanisms for the observed PM induced increases in cardiovascular morbidity and mortality. PMID- 26904260 TI - Mitral valve repair for ischemic mitral regurgitation: lessons from the Cardiothoracic Surgical Trials Network randomized study. AB - Approximately 30% to 50% of patients will develop ischemic mitral regurgitation (MR) after a myocardial infarction, which is a result of progressive left ventricular remodeling and dysfunction of the subvalvular apparatus, and portends a poor long-term prognosis. Surgical treatment is centered on mitral valve repair utilizing a restrictive annuloplasty, or valve replacement with preservation of the subvalvular apparatus. In the recent Cardiothoracic Surgical Trials Network (CSTN) study, patients with severe ischemic MR were randomized to mitral valve repair with a restrictive annuloplasty versus chordal-sparing valve replacement, and concomitant coronary artery bypass grafting, if indicated. At 2-year follow up, mitral valve repair was associated with a significantly higher incidence of moderate or greater recurrent MR and heart failure, with no difference in the indices of left ventricular reverse remodeling, as compared with valve replacement. The current appraisal aims to provide insight into the CSTN trial results, and discusses the evidence supporting a pathophysiologic-guided repair strategy incorporating combined annuloplasty and subvalvular repair techniques to optimize the outcomes of mitral valve repair in ischemic MR. PMID- 26904261 TI - Clinical update sleep: year in review 2015-2016. PMID- 26904262 TI - Otorhinolaryngological aspects of sleep-related breathing disorders. AB - Snoring and obstructive sleep apnoea (OSA) are disorders within a wide spectrum of sleep-related breathing disorders (SRBD). Given the obesity epidemic, these conditions will become increasingly prevalent and continue to serve as a large economic burden. A thorough clinical evaluation and appropriate investigations will allow stratification of patients into appropriate treatment groups. A multidisciplinary team is required to manage these patients. Patient selection is critical in ensuring successful surgical and non-surgical outcomes. A wide range of options are available and further long term prospective studies, with standardised data capture and outcome goals, are required to evaluate the most appropriate techniques and long term success rates. PMID- 26904263 TI - Update on paediatric obstructive sleep apnoea. AB - Obstructive sleep apnoea (OSA) is one of the most common causes of sleep disordered breathing (SDB) in children. It is associated with significant morbidity, potentially impacting on long-term neurocognitive and behavioural development, as well as cardiovascular outcomes and metabolic homeostasis. The low grade systemic inflammation and increased oxidative stress seen in this condition are believed to underpin the development of these OSA-related morbidities. The significant variance in degree of end organ morbidity in patients with the same severity of OSA highlights the importance of the interplay of genetic and environmental factors in determining the overall OSA phenotype. This review seeks to summarize the current understanding of the aetiology and mechanisms underlying OSA, its risk factors, diagnosis and treatment. PMID- 26904264 TI - Chronic obstructive pulmonary disease and obstructive sleep apnoea-the overlap syndrome. AB - Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnoea (OSA) are highly prevalent disorders and the co-existence of both disorders, termed the overlap syndrome, affects at least 1% of the adult population. Patients with the overlap syndrome typically experience more pronounced nocturnal oxygen desaturation and there is a high prevalence of pulmonary hypertension in such patients. Recent evidence suggests that the prevalence of each disorder together is higher than might be predicted by simple prevalence statistics, although the evidence is not clear-cut in this regard. Sleep itself can have several negative effects in patients with COPD. Sleep quality is diminished with reduced amounts of slow wave and rapid-eye-movement (REM) sleep, which may contribute to daytime symptoms such as fatigue and lethargy. Furthermore, normal physiological adaptations during sleep that result in mild hypoventilation in normal subjects are more pronounced in COPD, which can result in clinically important nocturnal oxygen desaturation. Management of sleep disorders in patients with COPD should address both sleep quality and disordered gas exchange. Non-invasive pressure support is beneficial in selected cases, particularly during acute exacerbations associated with respiratory failure, and is particularly helpful in patients with the overlap syndrome. There is limited evidence of benefit from pressure support in the chronic setting in COPD patients without OSA. PMID- 26904265 TI - The sympathetic nervous system and catecholamines metabolism in obstructive sleep apnoea. AB - Obstructive sleep apnoea (OSA) is the most common sleep disorder of breathing in middle-aged and overweight subjects. It features recurrent episodes of upper airway total (apnoea) o partial (hypopnea) collapse during sleep, which are associated with a reduction in blood oxygen saturation and with arousal from sleep to re-establish airway patency. An association of OSA with dysregulation of the autonomous nervous system (ANS) and altered catecholamines (CAs) metabolism has been contended for years. However, the pathophysiology mechanisms underlying these alterations remain to be fully clarified. Nonetheless, these alterations are deemed to play a key pathogenic role in the established association of OSA with several conditions besides arterial hypertension (HT), including coronary artery disease, stroke, and, more in general, with increased risk of cardiovascular (CV) events. Hence, in this review we will analyse the relationship between the sleep disturbances associated with OSA and the altered function of the ANS, including CAs metabolism. PMID- 26904266 TI - Update on clinical trials in home mechanical ventilation. AB - Home mechanical ventilation (HMV) is an increasingly common intervention and is initiated for a range of pathological processes, including neuromuscular disease (NMD), chronic obstructive pulmonary disease (COPD) and obesity related respiratory failure. There have been important recent data published in this area, which helps to guide practice by indicating which populations may benefit from this intervention and the optimum method of setting up and controlling sleep disordered breathing. Recent superficially conflicting data has been published regarding HMV in COPD, with a trial in post-exacerbation patients suggesting no benefit, but in stable chronic hypercapnic patients suggesting a clear and sustained mortality benefit. The two studies are critiqued and the potential reasons for the differing results are discussed. Early and small trial data is frequently contradicted with larger randomised controlled trials and this has been the case with diaphragm pacing being shown to be potentially harmful in the latest data, confirming the importance of non-invasive ventilation (NIV) in NMD such as motor neurone disease. Advances in ventilator technology have so far appeared quicker than the clinical data to support their use; although small and often unblinded, the current data suggests equivalence to standard modes of NIV, but with potential comfort benefits that may enhance adherence. The indications for NIV have expanded since its inception, with an effort to treat sleep disordered breathing as a result of chronic heart failure (HF). The SERVE-HF trial has recently demonstrated no clear advantage to this technology and furthermore detected a potentially deleterious effect, with a worsening of all cause and cardiovascular mortality in the treated group compared to controls. The review serves to provide the reader with a critical review of recent advances in the field of sleep disordered breathing and HMV. PMID- 26904267 TI - Screening for sleep-disordered breathing in a bariatric population. AB - BACKGROUND: Obstructive sleep apnea (OSA) is the most common form of sleep disordered breathing frequently associated with obesity. Obese subjects undergoing elective surgical procedures with general anesthesia are potentially at risk if this condition is not identified. Our aim was to assess the prevalence of bariatric patients with undiagnosed OSA following pre-operative assessment and who could benefit from peri-procedural respiratory management. METHODS: Patients who were referred for prospective bariatric surgery were screened using the STOP BANG questionnaire. If patients scored >4 points they underwent a home-based nocturnal pulse oximetry. Severity of OSA was defined by the 4% oxygen desaturation index (ODI) combined with a physician's review. Data were compared using unpaired two-tailed t-test and Chi-square test. Linear regression models were used to assess associations between clinical parameters. RESULTS: Sleep disordered breathing of any degree was evident in 103 of 141 patients (73%). Thirteen (9%) patients had severe, 19 (13%) moderate, and 34 (24%) mild OSA, 38 (27%) patients had no OSA. 34 (24%) patients were initiated on continuous positive airway pressure (CPAP) prior to the surgical procedure, 15 (11%) were admitted for further respiratory assessment and two of them were given CPAP following inpatient sleep study. Thirteen (9%) patients were advised to use a mandibular advancement device for mild but symptomatic OSA. Out of all patients, 76 (54%) were advised that no treatment was required. CONCLUSIONS: OSA is highly prevalent in a cohort of bariatric surgery patients screened with STOP-BANG questionnaires. Almost 3/4 of this cohort have at least some degree of sleep disordered breathing, and approximately half of them require a plan for the respiratory management perioperatively. PMID- 26904268 TI - In patients with minimally symptomatic OSA can baseline characteristics and early patterns of CPAP usage predict those who are likely to be longer-term users of CPAP. AB - BACKGROUND: Long-term continuous positive airway pressure (CPAP) usage varies between individuals. It would be of value to be able to identify those who are likely to benefit from CPAP (and use it long term), versus those who would not, and might therefore benefit from additional help early on. First, we explored whether baseline characteristics predicted CPAP usage in minimally symptomatic obstructive sleep apnoea (OSA) patients, a group who would be expected to have low usage. Second, we explored if early CPAP usage was predictive of longer-term usage, as has been shown in more symptomatic OSA patients. METHODS: The MOSAIC trial was a multi-centre randomised controlled trial where minimally symptomatic OSA patients were randomised to CPAP, or standard care, for 6 months. Here we have studied only those patients randomised to CPAP treatment. Baseline characteristics including symptoms, questionnaires [including the Epworth sleepiness score (ESS)] and sleep study parameters were recorded. CPAP usage was recorded at 2-4 weeks after initiation and after 6 months. The correlation and association between baseline characteristics and 6 months CPAP usage was assessed, as was the correlation between 2 and 4 weeks CPAP usage and 6 months CPAP usage. RESULTS: One hundred and ninety-five patients randomised to CPAP therapy had median [interquartile range (IQR)] CPAP usage of 2:49 (0:44, 5:13) h:min/night (h/n) at the 2-4 weeks visit, and 2:17 (0:08, 4:54) h/n at the 6 months follow-up visit. Only male gender was associated with increased long-term CPAP use (male usage 2:56 h/n, female 1:57 h/n; P=0.02). There was a moderate correlation between the usage of CPAP at 2-4 weeks and 6 months, with about 50% of the variability in long-term use being predicted by the short-term use. CONCLUSIONS: In patients with minimally symptomatic OSA, our study has shown that male gender (and not OSA severity or symptom burden) is associated with increased long-term use of CPAP at 6 months. Although, in general, early patterns of CPAP usage predicted longer term use, there are patients in whom this is not the case, and patients with low initial usage may need to extend their CPAP trial before a decision about longer-term use is made. PMID- 26904269 TI - The utility of a 5(th) nap in multiple sleep latency test. AB - BACKGROUND: This is the first study that aimed to look specifically at the utility of the 5(th) nap in the multiple sleep latency test (MSLT), a test used to assist in the diagnosis of narcolepsy. METHODS: Data was retrospectively collected from the Sleep Disorders Centre of a Tertiary Hospital on patients that had a 5(th) nap during their MSLT from the 08(th) November 2011 to 12(th) November 2014. RESULTS: Fifty-three patients had a 5(th) nap performed out of 378 MSLT studies. In 16% of cases a diagnosis of narcolepsy was given directly due to the inclusion of the 5(th) nap on the MSLT. Here a 5(th) nap allowed diagnostic criteria of mean sleep latency <8 minutes and >2 SOREMPS to be met. In 53% of cases the mean sleep latency increased due to 5(th) nap inclusion; the mean sleep latency of the first four naps was 5.6 vs. 6.7 after inclusion of the 5(th) nap. CONCLUSIONS: The 5(th) nap is not often performed within the MSLT studies. Our study shows that only a few patients may benefit from a 5(th) nap opportunity which also led to increase of the mean sleep latency at the expense of extra time, cost, labour and increased patient anxiety. PMID- 26904270 TI - Sleep, obesity and physicians' education. PMID- 26904271 TI - Influence of Endothelin-1 in Aqueous Humor on Intermediate-Term Trabeculectomy Outcomes. AB - Purpose. To investigate whether increased concentrations of ET-1 in aqueous humor of glaucoma patients influences surgical outcome of standard trabeculectomy with Mitomycin C. Methods. Retrospective chart review of 36 glaucoma patients with known ET-1 concentrations who had undergone trabeculectomy with Mitomycin C. Patients were divided into two groups based on their aqueous ET-1 concentration, a below-median (low ET-1) and an above-median (high ET-1) group. Postoperative IOP development, necessity of glaucoma medication, surgical success and complications, postoperative use of antifibrotics (5-FU), and number of additional glaucoma surgeries were compared between the groups. Results. Overall surgical success of trabeculectomy was comparable to published literature (90%, 81%, 76%, and 68% absolute success at 12, 24, 36, and 48 months after surgery). There was no difference between high and low ET-1 group in the postsurgical development of IOP, surgical success rate, or complication rate. There was no difference in postoperative scarring or indirect indicators thereof (e.g., number of 5-FU injections, needlings, suture lyses, or IOP lowering medications). Conclusion. In this set of patients, ET-1 in aqueous humor does not appear to have influenced surgical outcome of trabeculectomy with Mitomycin C. There is no indication of an increased likelihood of bleb fibrosis in patients with increased ET-1 concentrations. PMID- 26904272 TI - High Levels of 17beta-Estradiol Are Associated with Increased Matrix Metalloproteinase-2 and Metalloproteinase-9 Activity in Tears of Postmenopausal Women with Dry Eye. AB - Purpose. To determine the serum levels of sex steroids and tear matrix metalloproteinases (MMP) 2 and 9 concentrations in postmenopausal women with dry eye. Methods. Forty-four postmenopausal women with dry eye and 22 asymptomatic controls were enrolled. Blood was drawn and analyzed for serum levels of sex steroids and lipids. Then, the following tests were performed: tear collection, Ocular Surface Disease Index (OSDI) questionnaire, fluorescein tear film break-up time (TBUT), corneal fluorescein staining, Schirmer test, and conjunctival impression cytology. The conjunctival mRNA expression and tear concentrations of MMP-2 and MMP-9 were measured. Results. Serum 17beta-estradiol levels were significantly higher in the dry eye subjects than in the controls (P = 0.03), whereas there were no significant differences in levels of testosterone, dehydroepiandrosterone sulfate (DHEA-S), and progesterone. Tear MMP-2 and MMP-9 concentrations (P < 0.001), as well as the MMP-9 mRNA expression in conjunctival samples (P = 0.02), were significantly higher in dry eye subjects than in controls. Serum 17beta-estradiol levels were positively correlated with tear MMP 2 and MMP-9 concentrations and negatively correlated with Schirmer test values. Conclusions. High levels of 17beta-estradiol are associated with increased matrix metalloproteinase-2 and metalloproteinase-9 activity in tears of postmenopausal women with dry eye. PMID- 26904274 TI - Pupil Dilation with Intracameral Epinephrine Hydrochloride during Phacoemulsification and Intraocular Lens Implantation. AB - Objective. To investigate mydriatic effect of intracamerally injected epinephrine hydrochloride during phacoemulsification and intraocular lens (IOL) implantation. Methods. Eighteen cataract patients for bilateral phacoemulsification were enrolled. To dilate pupil, one eye was randomly selected to receive intracamerally 1 mL epinephrine hydrochloride 0.001% for 1 minute after corneal incision (intracameral group), and the contralateral eye received 3 drops of compound tropicamide 0.5% and phenylephrine 0.5% at 5-minute intervals 30 minutes before surgery (topical group). Pupil diameters were measured before corneal incision, before ophthalmic viscoelastic device (OVD) injection, after OVD injection, before IOL implantation, and at the end of surgery. Results. At each time point, the mean pupil diameter in the intracameral group was 2.20 +/- 0.08, 5.09 +/- 0.20, 6.76 +/- 0.19, 6.48 +/- 0.18, and 5.97 +/- 0.24 mm, respectively, and in the topical group it was 7.98 +/- 0.15, 7.98 +/- 0.15, 8.53 +/- 0.14, 8.27 +/- 0.16, and 7.93 +/- 0.20 mm, respectively. The topical group consistently had larger mydriatic effects than the intracameral group (P < 0.05). The onset of mydriatic effect was rapid in the intracameral group. There was no difference in surgical performance or other parameters between groups. Conclusions. Intracameral epinephrine hydrochloride appears to be an alternative to the mydriatic modalities for phacoemulsification and IOL implantation. In comparison with topical mydriatics, intracameral epinephrine hydrochloride offers easier preoperative preparation, more rapid pupil dilation, and comparable surgical performance. PMID- 26904273 TI - Relationship between Corneal Temperature and Intraocular Pressure in Healthy Individuals: A Clinical Thermographic Analysis. AB - Purpose. To study the geographical distribution of corneal temperature (CT) and its influence on the intraocular pressure (IOP) of healthy human volunteers. Materials and Methods. Fifteen subjects (7 M, 8 F), 33.8 +/- 17.4 years old, were enrolled in this pilot, cross-sectional study. Measurements of CT were taken after one hour with closed eyelids (CET) or closed eyelids with a cooling mask (cm-CET) and compared to baseline. Results. If compared to baseline, after CET, average CT significantly increased by 0.56 degrees C in the RE and by 0.48 degrees C in the LE (p < 0.001) and IOP concomitantly significantly increased by 1.13 mmHg and 1.46 mmHg, respectively, in each eye (p < 0.001). After cm-CET, average CT significantly decreased by 0.11 degrees C and 0.20 degrees C, respectively, in the RE and LE (RE p = 0.04; LE p = 0.024), followed by a significant IOP decrease of 2.19 mmHg and 1.54 mmHg, respectively, in each eye (RE p < 0.001; LE p = 0.0019). Conclusion. Significant variations of CT occurred after CET and cm-CET and were directly correlated with significant differences of IOP. It can be speculated that both oxidative stress and sympathetic nerve fiber stimulation by temperature oscillations may affect the regulation of AH vortex flow and turnover, thus influencing IOP values. PMID- 26904275 TI - A Head-Mounted Spectacle Frame for the Study of Mouse Lens-Induced Myopia. AB - The mouse model has been widely employed to explore the mysteries of myopia. For now, existing techniques for induction of experimental myopia in mice can be classified into three types: (1) devices directly glued to the fur; (2) devices attached using a combination of glue and sutures; (3) devices attached using a skull-mounted apparatus. These techniques each have its advantages, disadvantages when considering the devices stability, safety, complexity, effectiveness, and so forth. Thus, techniques for myopia induction in mice have yet to be further refined to popularize the applications. In this pilot study, we introduce a new head fixation device named the head-mounted spectacle frame apparatus for the study of mouse lens-induced myopia. Surgical procedures for device attachment were relatively simple and easy to learn in our study. Effective myopia induction was validated by retinoscopy refraction and axial length measurement using optical coherence tomography. In addition, it showed improved compliance and reliable safety when compared to the published methods. The head-mounted spectacle frame apparatus provides a new choice for the study of lens-induced myopia in mouse. It also allows for the use of form deprivation, making it attractive for future experimental mouse myopia trials. PMID- 26904276 TI - Characterization of a Hyperthermostable Alkaline Lipase from Bacillus sonorensis 4R. AB - Hyperthermostable alkaline lipase from Bacillus sonorensis 4R was purified and characterized. The enzyme production was carried out at 80 degrees C and 9.0 pH in glucose-tween inorganic salt broth under static conditions for 96 h. Lipase was purified by anion exchange chromatography by 12.15 fold with a yield of 1.98%. The molecular weight of lipase was found to be 21.87 KDa by SDS-PAGE. The enzyme activity was optimal at 80 degrees C with t 1/2 of 150 min and at 90 degrees C, 100 degrees C, 110 degrees C, and 120 degrees C; the respective values were 121.59 min, 90.01 min, 70.01 min, and 50 min. The enzyme was highly activated by Mg and t 1/2 values at 80 degrees C were increased from 150 min to 180 min when magnesium and mannitol were added in combination. The activation energy calculated from Arrhenius plot was 31.102 KJ/mol. At 80-120 degrees C, values of DeltaH and DeltaG were in the range of 28.16-27.83 KJ/mol and 102.79 KJ/mol to 111.66 KJ/mol, respectively. Lipase activity was highest at 9.0 pH and stable for 2 hours at this pH at 80 degrees C. Pretreatment of lipase with MgSO4 and CaSO4 stimulated enzyme activity by 249.94% and 30.2%, respectively. The enzyme activity was greatly reduced by CoCl2, CdCl2, HgCl2, CuCl2, Pb(NO3)2, PMSF, orlistat, oleic acid, iodine, EDTA, and urea. PMID- 26904277 TI - The Obesity Paradox and Heart Failure: A Systematic Review of a Decade of Evidence. AB - There is scientific consensus that obesity increases the risk of cardiovascular diseases, including heart failure. However, among persons who already have heart failure, outcomes seem to be better in obese persons as compared with lean persons: this has been termed the obesity paradox, the mechanisms of which remain unclear. This study systematically reviewed the evidence of the relationship between heart failure mortality (and survival) and weight status. Search of the PubMed/MEDLINE and EMBASE databases was done according to the PRISMA protocol. The initial search identified 9879 potentially relevant papers, out of which ten studies met the inclusion criteria. One study was a randomized clinical trial and 9 were observational cohort studies: 6 prospective and 3 retrospective studies. All studies used the BMI, WC, or TSF as measure of body fatness and NYHA Classification of Heart Failure and had single outcomes, death, as study endpoint. All studies included in review were longitudinal studies. All ten studies reported improved outcomes for obese heart failure patients as compared with their normal weight counterparts; worse prognosis was demonstrated for extreme obesity (BMI > 40 kg/m(2)). The findings of this review will be of significance in informing the practice of asking obese persons with heart failure to lose weight. However, any such recommendation on weight loss must be consequent upon more conclusive evidence on the mechanisms of the obesity paradox in heart failure and exclusion of collider bias. PMID- 26904278 TI - Effects of 8-Prenylnaringenin and Whole-Body Vibration Therapy on a Rat Model of Osteopenia. AB - Background. 8-Prenylnaringenin (8-PN) is the phytoestrogen with the highest affinity for estrogen receptor-alpha (ER-alpha), which is required to maintain BMD. The osteoprotective properties of 8-PN have been demonstrated previously in tibiae. We used a rat osteopenia model to perform the first investigation of 8-PN with whole-body vertical vibration (WBVV). Study Design. Ovariectomy was performed on 52 of 64 Sprague-Dawley rats. Five weeks after ovariectomy, one group received daily injections (sc) of 8-PN (1.77 mg/kg) for 10 weeks; a second group was treated with both 8-PN and WBVV (twice a day, 15 min, 35 Hz, amplitude 0.47 mm). Other groups received either only WBVV or no treatment. Methods. The rats were sacrificed 15 weeks after ovariectomy. Lumbar vertebrae and femora were removed for biomechanical and morphological assessment. Results. 8-PN at a cancer safe dose did not cause fundamental improvements in osteoporotic bones. Treatment with 8-PN caused a slight increase in uterine wet weight. Combined therapy using WBVV and 8-PN showed no significant improvements in bone structure and biomechanical properties. Conclusion. We cannot confirm the osteoprotective effects of 8-PN at a cancer-safe dose in primary affected osteoporotic bones. Higher concentrations of 8-PN are not advisable for safety reasons. Adjunctive therapy with WBVV demonstrates no convincing effects on bones. PMID- 26904280 TI - Epidemiology of Acute Symptomatic Seizures among Adult Medical Admissions. AB - Acute symptomatic seizures are seizures occurring in close temporal relationship with an acute central nervous system (CNS) insult. The objective of the study was to determine the frequency of presentation and etiological risk factors of acute symptomatic seizures among adult medical admissions. It was a two-year retrospective study of the medical files of adults patients admitted with acute symptomatic seizures as the first presenting event. There were 94 cases of acute symptomatic seizures accounting for 5.2% (95% CI: 4.17-6.23) of the 1,802 medical admissions during the period under review. There were 49 (52.1%) males and 45 (47.9%) females aged between 18 years and 84 years. The etiological risk factors of acute symptomatic seizures were infections in 36.2% (n = 34) of cases, stroke in 29.8% (n = 28), metabolic in 12.8% (n = 12), toxic in 10.6% (n = 10), and other causes in 10.6% (n = 10). Infective causes were more among those below fifty years while stroke was more in those aged fifty years and above. CNS infections and stroke were the prominent causes of acute symptomatic seizures. This is an evidence of the "double tragedy" facing developing countries, the unresolved threat of infectious diseases on one hand and the increasing impact of noncommunicable diseases on the other one. PMID- 26904279 TI - Absorption, Metabolism, and Excretion by Freely Moving Rats of 3,4-DHPEA-EDA and Related Polyphenols from Olive Fruits (Olea europaea). AB - Absorption, metabolism, and excretion of 3,4-DHPEA-EDA, oleuropein, and hydroxytyrosol isolated from olive fruits were newly evaluated after oral and intravenous administration in freely moving rats cannulated in the portal vein, jugular vein, and bile duct. Orally administered 3,4-DHPEA-EDA, an important bioactive compound in olive pomace, was readily absorbed and metabolized to hydroxytyrosol, homovanillic acid, and homovanillyl alcohol, as shown by dose normalized 4 h area under the curve (AUC0->4 h/Dose) values of 27.7, 4.5, and 4.2 MUM.min.kg/MUmol, respectively, in portal plasma after oral administration. The parent compound 3,4-DHPEA-EDA was not observed in the portal plasma, urine, and bile after oral and intravenous administration. Additionally, hydroxytyrosol, homovanillic acid, and homovanillyl alcohol in the portal plasma after oral administration of hydroxytyrosol showed 51.1, 22.8, and 7.1 MUM.min.kg/MUmol AUC0 >4 h/Dose, respectively. When oleuropein, a polar glucoside, was injected orally, oleuropein in the portal plasma showed 0.9 MUM.min.kg/MUmol AUC0->4 h/Dose. However, homovanillic acid was detected from oleuropein in only a small amount in the portal plasma. Moreover, the bioavailability of hydroxytyrosol and oleuropein for 4 hours was 13.1% and 0.5%, respectively. Because the amount of 3,4-DHPEA-EDA in olive fruits is about 2-3 times greater than that of hydroxytyrosol, the metabolites of 3,4-DHPEA-EDA will influence biological activities. PMID- 26904281 TI - Seroprevalence and Predictors of Hepatitis B Virus Infection among Pregnant Women Attending Routine Antenatal Care in Arba Minch Hospital, South Ethiopia. AB - Hepatitis B virus (HBV) is a serious cause of liver disease affecting millions of people throughout the world. When HBV is acquired during pregnancy, prenatal transmission can occur to the fetus. Therefore, this study is aimed at estimating seroprevalence and associated factors of HBV infection among pregnant women attending Antenatal Clinic (ANC) of Arba Minch Hospital, Southern Ethiopia. A facility based cross-sectional study was conducted on 232 pregnant women visiting ANC from February to April, 2015. Data regarding sociodemographic and associated factors were gathered using questionnaire. Serum samples were tested for hepatitis B surface antigen (HBsAg) by Enzyme Linked Immunosorbent Assay. Data was analyzed using SPSS version 20. The overall seroprevalence of HBV infection was 4.3% (95% CI: 2.2-6.9%). Multivariate analysis showed that history of abortion (AOR = 7.775; 95% CI: 1.538-39.301) and having multiple sexual partners (AOR = 7.189; 95% CI: 1.039-49.755) were independent predictors of HBsAg seropositivity. In conclusion, the prevalence of HBV infection is intermediate. Therefore, screening HBV infection should be routine part of ANC; health information on having single sexual partner for women of childbearing age and on following aseptic techniques during abortion should be provided to health facilities working on abortion. PMID- 26904283 TI - The Incidence of Peripheral Catheter-Related Thrombosis in Surgical Patients. AB - Background. Central venous catheters and peripherally inserted central catheters are well established risk factors for upper limb deep vein thrombosis. There is limited literature on the thrombosis rates in patients with peripheral catheters. A prospective observational study was conducted to determine the incidence of peripheral catheter-related thrombosis in surgical patients. Methods. Patients deemed high risk for venous thrombosis with a peripheral catheter were considered eligible for the study. An ultrasound was performed on enrolment into the study and at discharge from hospital. Participants were reviewed twice a day for clinical features of upper limb deep vein thrombosis during their admission and followed up at 30 days. Results. 54 patients were included in the study. The incidence of deep vein thrombosis and superficial venous thrombosis was 1.8% and 9.2%, respectively. All cases of venous thrombosis were asymptomatic. Risk factor analysis was limited by the low incidence of thrombosis. Conclusion. This study revealed a low incidence of deep vein thrombosis in surgical patients with peripheral catheters (1.8%). The study was underpowered; therefore the association between peripheral catheters and thrombosis is unable to be established. Future studies with larger sample sizes are required to determine the association between peripheral catheters and thrombosis. PMID- 26904282 TI - The Role of Current Techniques and Concepts in Peripheral Nerve Repair. AB - Patients with peripheral nerve injuries, especially severe injury, often face poor nerve regeneration and incomplete functional recovery, even after surgical nerve repair. This review summarizes treatment options of peripheral nerve injuries with current techniques and concepts and reviews developments in research and clinical application of these therapies. PMID- 26904284 TI - Improving System Integration: The Art and Science of Engaging Small Community Practices in Health System Innovation. AB - This paper focuses on successful engagement strategies in recruiting and retaining primary care physicians (PCPs) in a quality improvement project, as perceived by family physicians in small practices. Sustained physician engagement is critical for quality improvement (QI) aiming to enhance health system integration. Although there is ample literature on engaging physicians in hospital or team-based practice, few reports describe factors influencing engagement of community-based providers practicing with limited administrative support. The PCPs we describe participated in SCOPE: Seamless Care Optimizing the Patient Experience, a QI project designed to support their care of complex patients and reduce both emergency department (ED) visits and inpatient admissions. SCOPE outcome measures will inform subsequent papers. All the 30 participating PCPs completed surveys assessing perceptions regarding the importance of specific engagement strategies. Project team acknowledgement that primary care is challenging and new access to patient resources were the most important factors in generating initial interest in SCOPE. The opportunity to improve patient care via integration with other providers was most important in their commitment to participate, and a positive experience with project personnel was most important in their continued engagement. Our experience suggests that such providers respond well to personalized, repeated, and targeted engagement strategies. PMID- 26904285 TI - Antibacterial Properties of Alkaloid Extracts from Callistemon citrinus and Vernonia adoensis against Staphylococcus aureus and Pseudomonas aeruginosa. AB - The development of new antibiotics from new chemical entities is becoming more and more expensive, time-consuming, and compounded by emerging strains that are drug resistant. Alkaloids are plant secondary metabolites which have been shown to have potent pharmacological activities. The effect of alkaloids from Callistemon citrinus and Vernonia adoensis leaves on bacterial growth and efflux pump activity was evaluated on Staphylococcus aureus and Pseudomonas aeruginosa. At a concentration of 1.67 mg/mL, the alkaloids inhibited bacterial growth with comparable effects to ampicillin, a standard antibiotic. The alkaloids from C. citrinus were the most potent against S. aureus with an MIC of 0.0025 mg/mL and MBC of 0.835 mg/mL. It was shown that effects on P. aeruginosa by both plant alkaloids were bacteriostatic. P. aeruginosa was most susceptible to drug efflux pump inhibition by C. citrinus alkaloids which caused an accumulation of Rhodamine 6G of 121% compared to the control. Thus, C. citrinus alkaloids showed antibacterial activity as well as inhibiting ATP-dependent transport of compounds across the cell membrane. These alkaloids may serve as potential courses of compounds that can act as lead compounds for the development of plant-based antibacterials and/or their adjunct compounds. PMID- 26904286 TI - Protective Effects of Carvacrol against Oxidative Stress Induced by Chronic Stress in Rat's Brain, Liver, and Kidney. AB - Restraint stress may be associated with elevated free radicals, and thus, chronic exposure to oxidative stress may cause tissue damage. Several studies have reported that carvacrol (CAR) has a protective effect against oxidative stress. The present study was designed to investigate the protective effects of CAR on restraint stress induced oxidative stress damage in the brain, liver, and kidney. For chronic restraint stress, rats were kept in the restrainers for 6 h every day, for 21 consecutive days. The animals received systemic administrations of CAR daily for 21 days. To evaluate the changes of the oxidative stress parameters following restraint stress, the levels of malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), and catalase (CAT) activities were measured in the brain, liver, and kidney. In the stressed animals that received vehicle, the MDA level was significantly higher (P < 0.001) and the levels of GSH and antioxidant enzymes were significantly lower than the nonstressed animals (P < 0.001). CAR ameliorated the changes in the stressed animals as compared with the control group (P < 0.001). This study indicates that CAR can prevent restraint stress induced oxidative damage. PMID- 26904287 TI - Modulation of Erythrocyte Plasma Membrane Redox System Activity by Curcumin. AB - Plasma membrane redox system (PMRS) is an electron transport chain system ubiquitously present throughout all cell types. It transfers electron from intracellular substrates to extracellular acceptors for regulation of redox status. Curcumin, isolated from Curcuma longa, has modulatory effects on cellular physiology due to its membrane interaction ability and antioxidant potential. The present study investigates the effect of curcumin on PMRS activity of erythrocytes isolated from Wistar rats in vitro and in vivo and validated through an in silico docking simulation study using Molegro Virtual Docker (MVD). Effects of curcumin were also evaluated on level of glutathione (GSH) and the oxidant potential of plasma measured in terms of plasma ferric equivalent oxidative potentials (PFEOP). Results show that curcumin significantly (p < 0.01) downregulated the PMRS activity in a dose-dependent manner. Molecular docking results suggest that curcumin interacts with amino acids at the active site cavity of cytochrome b 5 reductase, a key constituent of PMRS. Curcumin also increased the GSH level in erythrocytes and plasma while simultaneously decreasing the oxidant potential (PFEOP) of plasma. Altered PMRS activity and redox status are associated with the pathophysiology of several health complications including aging and diabetes; hence, the above finding may explain part of the role of curcumin in health beneficial effects. PMID- 26904288 TI - Evaluation of Early Markers of Nephropathy in Patients with Type 2 Diabetes Mellitus. AB - Aims. T2DM often remains undiagnosed for many years because hyperglycemia develops gradually and may not produce any symptoms. As patients with T2DM are at increased risk of microvascular and macrovascular complications, the preclinical diagnosis of the state is the key point of the disease management. Methods. We evaluated parameters such as GAGs/PGs, NAG, and NGAL in urine samples from 43 normoalbuminuric T2DM patients and 31 apparently healthy control subjects. Results. The total urinary GAG excretion showed no significant differences between patients and controls. The electrophoretic analysis evidenced the presence of UTI and its degradation products (LSC and SM-LSC), CS, and HS. We observed modifications of HS and total UTI (including UTI and its degradation products) relative contents in T2DM patients compared with controls whereas no differences in CS percentage were found. NGAL levels were significantly increased in T2DM patients and were positively correlated with both NAG (r = 0.606, p < 0.0001) and the presence of hypertension (r = 0.352, p < 0.05). Conclusions. These data suggest that the assessed molecules could represent useful markers to detect early renal impairment in patients with T2DM. PMID- 26904289 TI - Phenotypic and Functional Changes of Endothelial and Smooth Muscle Cells in Thoracic Aortic Aneurysms. AB - Thoracic aortic aneurysm develops as a result of complex series of events that alter the cellular structure and the composition of the extracellular matrix of the aortic wall. The purpose of the present work was to study the cellular functions of endothelial and smooth muscle cells from the patients with aneurysms of the thoracic aorta. We studied endothelial and smooth muscle cells from aneurysms in patients with bicuspid aortic valve and with tricuspid aortic valve. The expression of key markers of endothelial (CD31, vWF, and VE-cadherin) and smooth muscle (SMA, SM22alpha, calponin, and vimentin) cells as well extracellular matrix and MMP activity was studied as well as and apoptosis and cell proliferation. Expression of functional markers of endothelial and smooth muscle cells was reduced in patient cells. Cellular proliferation, migration, and synthesis of extracellular matrix proteins are attenuated in the cells of the patients. We show for the first time that aortic endothelial cell phenotype is changed in the thoracic aortic aneurysms compared to normal aortic wall. In conclusion both endothelial and smooth muscle cells from aneurysms of the ascending aorta have downregulated specific cellular markers and altered functional properties, such as growth rate, apoptosis induction, and extracellular matrix synthesis. PMID- 26904290 TI - Retrievable Inferior Vena Cava Filters in Patients with Cancer: Complications and Retrieval Success Rate. AB - Active cancer (ACa) is strongly associated with venous thromboembolism and bleeding. Retrievable inferior vena cava filters (RIVCF) are frequently placed in these patients when anticoagulation cannot be continued. Objectives. To describe the complications and retrieval rate of inferior vena cava filters in patients with ACa. Methods. Retrospective review of 251 consecutive patients with RIVCF in a single institution. Results. We included 251 patients with RIVCF with a mean age of 58.1 years and a median follow-up of 5.4 months (164 days, IQR: 34-385). Of these patients 32% had ACa. There were no differences in recurrence rate of DVT between patients with ACa and those without ACa (13% versus 17%, p = ns). Also, there were no differences in major filter complications (11% ACa versus 7% no ACa, p = ns). The filter retrieval was not different between groups (log-rank = 0.16). Retrieval rate at 6 months was 49% in ACa patients versus 64% in patients without ACa (p = ns). Filter retrieval was less frequent in ACa patients with metastatic disease (p < 0.01) or a nonsurgical indication for filter placement (p = 0.04). Conclusions. No differences were noted in retrieval rate, recurrent DVT, or filter complications between the two groups. ACa should not preclude the use of RIVCF. PMID- 26904291 TI - Vascular Health in American Football Players: Cardiovascular Risk Increased in Division III Players. AB - Studies report that football players have high blood pressure (BP) and increased cardiovascular risk. There are over 70,000 NCAA football players and 450 Division III schools sponsor football programs, yet limited research exists on vascular health of athletes. This study aimed to compare vascular and cardiovascular health measures between football players and nonathlete controls. Twenty-three athletes and 19 nonathletes participated. Vascular health measures included flow mediated dilation (FMD) and carotid artery intima-media thickness (IMT). Cardiovascular measures included clinic and 24 hr BP levels, body composition, VO2 max, and fasting glucose/cholesterol levels. Compared to controls, football players had a worse vascular and cardiovascular profile. Football players had thicker carotid artery IMT (0.49 +/- 0.06 mm versus 0.46 +/- 0.07 mm) and larger brachial artery diameter during FMD (4.3 +/- 0.5 mm versus 3.7 +/- 0.6 mm), but no difference in percent FMD. Systolic BP was significantly higher in football players at all measurements: resting (128.2 +/- 6.4 mmHg versus 122.4 +/- 6.8 mmHg), submaximal exercise (150.4 +/- 18.8 mmHg versus 137.3 +/- 9.5 mmHg), maximal exercise (211.3 +/- 25.9 mmHg versus 191.4 +/- 19.2 mmHg), and 24-hour BP (124.9 +/- 6.3 mmHg versus 109.8 +/- 3.7 mmHg). Football players also had higher fasting glucose (91.6 +/- 6.5 mg/dL versus 86.6 +/- 5.8 mg/dL), lower HDL (36.5 +/- 11.2 mg/dL versus 47.1 +/- 14.8 mg/dL), and higher body fat percentage (29.2 +/- 7.9% versus 23.2 +/- 7.0%). Division III collegiate football players remain an understudied population and may be at increased cardiovascular risk. PMID- 26904292 TI - Psychometric Properties of the Hindi Version of the Disabilities of Arm, Shoulder, and Hand: A Pilot Study. AB - Objectives. To culturally adapt and translate the Disabilities of Arm, Shoulder, and Hand questionnaire into Hindi (DASH-H) and assess its reliability, validity, and responsiveness in adult patients with shoulder tendonitis. Study Design. Descriptive methodological research, using longitudinal design. Setting. Outpatient clinic. Participants. 30 adult patients aged 53.3 +/- 6.9 y with shoulder tendonitis. Data Analyses. DASH-H, visual analogue scales for pain (VAS P) and disability (VAS-D), and shoulder active range of motion (AROM) were assessed at baseline, 2-3 days later, and 4-5 weeks after baseline. Intraclass correlation coefficients (ICC) assessed test-retest reliability of these scales and responsiveness was examined by calculating effect sizes (ES) and standardized response means (SRM). Cronbach's alpha (CA) was used to examine internal consistency of DASH-H. Convergent construct validity of DASH-H with VAS scales and shoulder AROM was determined using Pearson's Correlation Coefficients (r). Results. DASH-H demonstrated good test-retest reliability and internal consistency (ICC and CA both > 0.75) and excellent responsiveness (ES = 2.2, SRM = 6.1). DASH-H showed high concordance (r = -0.71, p < 0.01) with AROM-flexion and moderate concordance (r > -0.4, p < 0.05) with VAS scales and AROM-external rotation. Conclusion. Analyses indicate that DASH-H demonstrates good test-retest reliability, validity, and responsiveness in patients with shoulder tendonitis. PMID- 26904293 TI - Shouldering the Burden of Evidence-Based Practice: The Experiences of Physiotherapists Partaking in a Community of Practice. AB - The study aim was to elicit the motivators, barriers, and benefits of participation in a Community of Practice (CoP) for primary care physiotherapists. We used a qualitative approach using semistructured interviews. The participants were twelve physiotherapists partaking in a newly formed Shoulder CoP. A desire for peer support was the strongest motivator for joining, with improving clinical practice being less apparent. Barriers to participation included time and work pressures and poor research skills. The structure of the CoP, in terms of access to meetings and the provision of preparation work and deadlines for the journal clubs, was reported to be a facilitator. Multiple benefits ensued from participation. The role of teamwork was emphasised in relation to reducing isolation and achieving goals. The majority of participants reported positive clinical practice changes in terms of improved patient education, increased confidence, and availability of new resources. All participants reported some element of personal growth and development, in particular in their evidence-based practice skills. The results provide support for the use of CoPs as a means of continuing professional development for physiotherapists in the workplace, as significant benefits are gained in terms of evidence-based practice (EBP), patient care, and therapist personal development. PMID- 26904294 TI - PEG-Immobilized Keratin for Protein Drug Sequestration and pH-Mediated Delivery. AB - Protein drugs like growth factors are promising therapeutics for damaged-tissue repair. Their local delivery often requires biomaterial carriers for achieving the therapeutic dose range while extending efficacy. In this study, polyethylene glycol (PEG) and keratin were crosslinked and used as sponge-like scaffolds (KTN PEG) to absorb test proteins with different isoelectric points (pI): albumin (~5), hemoglobin (~7), and lysozyme (~11). The protein release kinetics was influenced by charge at physiological pH 7.4. The keratin network, with pI 5.3, electrostatically attracted lysozyme and repulsed albumin generating the release rate profile: albumin > hemoglobin > lysozyme. However, under acidic conditions (pH 4), all proteins including keratins were positively charged and consequently intermolecular repulsion altered the release hierarchy, now determined by size (MW) diffusion: lysozyme (14 kDa) > hemoglobin (64 kDa) > albumin (66 kDa). Vascular endothelial growth factor C (VEGF-C), with properties comparable to lysozyme, was absorbed into the KTN-PEG scaffold. Endothelial cells cultured on this substrate had significantly larger numbers than on scaffolds without VEGF-C suggesting that the ionically bound and retained growth factor at neutral pH indirectly increased acute cell attachment and viability. PEG and keratin based sequestrations of proteins with basic pIs are therefore a feasible strategy with potential applications for selective biologics delivery. PMID- 26904295 TI - Synergistic Effects of Plant Growth Promoting Rhizobacteria and Chitosan on In Vitro Seeds Germination, Greenhouse Growth, and Nutrient Uptake of Maize (Zea mays L.). AB - This study aimed to assess the effects of three plant growth promoting rhizobacteria (PGPR) and chitosan either singly or in combination on maize seeds germination and growth and nutrient uptake. Maize seeds were treated with chitosan and bacterial solution. The germination and growth tests were carried out in square Petri dishes and plastic pots. The combination chitosan-A. lipoferum-P. fluorescens has increased the seeds vigor index up to 36.44% compared to the control. In comparison to the control, P. putida has significantly improved root weight (44.84%) and germinated seed weight (31.39%) whereas chitosan-P. putida has increased the shoot weight (65.67%). For the growth test, the maximal heights (17.66%) were obtained by plants treated with the combination A. lipoferum-P. fluorescens-P. putida. Chitosan-P. fluorescens induced the highest increases of leaves per plant (50.09%), aerial (84.66%), and underground biomass (108.77%) production. The plants inoculated with A. lipoferum had the large leaf areas with an increase of 54.08%, while combinations P. fluorescens-P. putida and chitosan-A. lipoferum improved the aerial and underground dry matter of plants to 26.35% and 18.18%. The nitrogen content of the plants was increased by chitosan-A. lipoferum-P. fluorescens-P. putida with an increasing of 41.61%. The combination of chitosan and PGPR can be used as biological fertilizers to increase maize production. PMID- 26904296 TI - Relationship of Routine Inadequate Sleep Duration and Periodontitis in a Nationally Representative Sample. AB - Purpose. Previous research has indicated the public health impact of inadequate sleep duration on health, potentially through an immune-inflammation mechanism. This mechanism also has a role in periodontitis. The purpose of this study is to determine if there is an association of routine inadequate sleep and periodontitis. Methods. Data from merged National Health and Nutrition Examination Survey years 2009-10 and 2011-12 were the data source for the study. The key outcome was periodontitis (yes, no), and the key variable of interest was usual sleep on weekday or workday nights. Chi square and logistic regression procedures were conducted. The study included 3,740 participants who were of ages 30 years and above. Results. There were 52.7% of participants who had periodontitis. There were 35.7% who usually slept less than 7 hours on weekday or workday nights. In adjusted logistic regression the odds ratio for periodontal disease for participants who slept less than 7 hours on weekday or workday night was 1.00 [95% confidence interval: 0.83, 1.21; p = .9812]. Conclusions. The relationship of periodontitis and inadequate sleep duration in a nationally representative study of participants who were of ages 30 years and above failed to reach statistical significance in adjusted logistic regression analyses. PMID- 26904298 TI - Inducing LTD-Like Effect in the Human Motor Cortex with Low Frequency and Very Short Duration Paired Associative Stimulation: An Exploratory Study. AB - Introduction. Paired associative stimulation (PAS) is an established technique to investigate synaptic plasticity in the human motor cortex (M1). Classically, to induce long-term depression- (LTD-) or long-term potentiation-like effects in the human M1, studies have used low frequency and long duration trains of PAS. In the present study, we explored an LTD-like effect using very short duration and low frequency of PAS10 ms protocols in human M1. Methods. Six protocols of low frequency PAS10 ms (ranging from 0.2 Hz to 1 Hz) were investigated with very short durations of 1 and 2 minutes stimulation. Six healthy volunteers were included in each protocol. We obtained motor-evoked potentials from right abductor pollicis brevis muscle before and after applying PAS10 ms up to 30 minutes. After we found PAS10 ms protocol which induced an LTD-like effect, we tested that protocol on additional 5 subjects. Results. One-way repeated-measures ANOVA showed that only the group of 1-minute stimulation of 0.25 Hz induced an LTD-like effect. When adding the additional subjects, the effect remained and lasted for 30 minutes. Conclusion. Low frequency and very short duration of PAS10 ms potentially induced an LTD-like effect in human M1. With further verification, this method might be useful for research relating to synaptic plasticity by reducing the duration of study and minimizing subject discomfort. PMID- 26904297 TI - Proteostasis and RNA Binding Proteins in Synaptic Plasticity and in the Pathogenesis of Neuropsychiatric Disorders. AB - Decades of research have demonstrated that rapid alterations in protein abundance are required for synaptic plasticity, a cellular correlate for learning and memory. Control of protein abundance, known as proteostasis, is achieved across a complex neuronal morphology that includes a tortuous axon as well as an extensive dendritic arbor supporting thousands of individual synaptic compartments. To regulate the spatiotemporal synthesis of proteins, neurons must efficiently coordinate the transport and metabolism of mRNAs. Among multiple levels of regulation, transacting RNA binding proteins (RBPs) control proteostasis by binding to mRNAs and mediating their transport and translation in response to synaptic activity. In addition to synthesis, protein degradation must be carefully balanced for optimal proteostasis, as deviations resulting in excess or insufficient abundance of key synaptic factors produce pathologies. As such, mutations in components of the proteasomal or translational machinery, including RBPs, have been linked to the pathogenesis of neurological disorders such as Fragile X Syndrome (FXS), Fragile X Tremor Ataxia Syndrome (FXTAS), and Autism Spectrum Disorders (ASD). In this review, we summarize recent scientific findings, highlight ongoing questions, and link basic molecular mechanisms to the pathogenesis of common neuropsychiatric disorders. PMID- 26904299 TI - Programming of Dopaminergic Neurons by Neonatal Sex Hormone Exposure: Effects on Dopamine Content and Tyrosine Hydroxylase Expression in Adult Male Rats. AB - We sought to determine the long-term changes produced by neonatal sex hormone administration on the functioning of midbrain dopaminergic neurons in adult male rats. Sprague-Dawley rats were injected subcutaneously at postnatal day 1 and were assigned to the following experimental groups: TP (testosterone propionate of 1.0 mg/50 MUL); DHT (dihydrotestosterone of 1.0 mg/50 MUL); EV (estradiol valerate of 0.1 mg/50 MUL); and control (sesame oil of 50 MUL). At postnatal day 60, neurochemical studies were performed to determine dopamine content in substantia nigra-ventral tegmental area and dopamine release in nucleus accumbens. Molecular (mRNA expression of tyrosine hydroxylase) and cellular (tyrosine hydroxylase immunoreactivity) studies were also performed. We found increased dopamine content in substantia nigra-ventral tegmental area of TP and EV rats, in addition to increased dopamine release in nucleus accumbens. However, neonatal exposure to DHT, a nonaromatizable androgen, did not affect midbrain dopaminergic neurons. Correspondingly, compared to control rats, levels of tyrosine hydroxylase mRNA and protein were significantly increased in TP and EV rats but not in DHT rats, as determined by qPCR and immunohistochemistry, respectively. Our results suggest an estrogenic mechanism involving increased tyrosine hydroxylase expression, either by direct estrogenic action or by aromatization of testosterone to estradiol in substantia nigra-ventral tegmental area. PMID- 26904300 TI - Carbachol-Induced Reduction in the Activity of Adult Male Zebra Finch RA Projection Neurons. AB - Cholinergic mechanism is involved in motor behavior. In songbirds, the robust nucleus of the arcopallium (RA) is a song premotor nucleus in the pallium and receives cholinergic inputs from the basal forebrain. The activity of projection neurons in RA determines song motor behavior. Although many evidences suggest that cholinergic system is implicated in song production, the cholinergic modulation of RA is not clear until now. In the present study, the electrophysiological effects of carbachol, a nonselective cholinergic receptor agonist, were investigated on the RA projection neurons of adult male zebra finches through whole-cell patch-clamp techniques in vitro. Our results show that carbachol produced a significant decrease in the spontaneous and evoked action potential (AP) firing frequency of RA projection neurons, accompanying a hyperpolarization of the membrane potential, an increase in the evoked AP latency, afterhyperpolarization (AHP) peak amplitude, and AHP time to peak, and a decrease in the membrane input resistance, membrane time constant, and membrane capacitance. These results indicate that carbachol reduces the activity of RA projection neurons by hyperpolarizing the resting membrane potential and increasing the AHP and the membrane conductance, suggesting that the cholinergic modulation of RA may play an important role in song production. PMID- 26904301 TI - Caught in the Net: Perineuronal Nets and Addiction. AB - Exposure to drugs of abuse induces plasticity in the brain and creates persistent drug-related memories. These changes in plasticity and persistent drug memories are believed to produce aberrant motivation and reinforcement contributing to addiction. Most studies have explored the effect drugs of abuse have on pre- and postsynaptic cells and astrocytes; however, more recently, attention has shifted to explore the effect these drugs have on the extracellular matrix (ECM). Within the ECM are unique structures arranged in a net-like manner, surrounding a subset of neurons called perineuronal nets (PNNs). This review focuses on drug-induced changes in PNNs, the molecules that regulate PNNs, and the expression of PNNs within brain circuitry mediating motivation, reward, and reinforcement as it pertains to addiction. PMID- 26904303 TI - Complex Perioperative Decision-Making: Liver Resection in a Patient with Extensive Superior Vena Cava/Right Atrial Thrombus and Superior Vena Cava Syndrome. AB - The perioperative management of patients suffering from extensive superior vena cava (SVC) thrombus complicated by SVC syndrome presents unique challenges. The anesthesiologist needs to be prepared for possible thrombus dislodgement resulting in pulmonary embolism and also has to assess the need for fluid resuscitation given the dangers of massive intravenous fluid application via the upper extremities. We present our perioperative approach in management of a patient scheduled for right hepatectomy who was previously diagnosed with extensive SVC and right atrial (RA) thrombus complicated by SVC syndrome. PMID- 26904304 TI - Workup and Management of Persistent Neuralgia following Nerve Block. AB - Neurological injuries following peripheral nerve blocks are a relatively rare yet potentially devastating complication depending on the type of lesion, affected extremity, and duration of symptoms. Medical management continues to be the treatment modality of choice with multimodal nonopioid analgesics as the cornerstone of this therapy. We report the case of a 28-year-old man who developed a clinical common peroneal and lateral sural cutaneous neuropathy following an uncomplicated popliteal sciatic nerve block. Workup with electrodiagnostic studies and magnetic resonance neurography revealed injury to both the femoral and sciatic nerves. Diagnostic studies and potential mechanisms for nerve injury are discussed. PMID- 26904305 TI - Hypereosinophilic Syndrome: A Case of Fatal Loffler Endocarditis. AB - Hypereosinophilic syndrome (HES) is a rare disorder with unknown global prevalence, barely reported in Hispanic population, and characterized by persistent eosinophilia in association with organ dysfunctions directly attributable to eosinophilic infiltration. Cardiac involvement may be present in 50 to 60% of the patients. This is known as Loffler endocarditis. We present a case of a 36-year-old Hispanic man with signs of heart failure. Laboratory studies showed eosinophilia (23,100/MUL). Thoracic computer tomography showed bilateral pleural effusion and a large left ventricular mass. Transthoracic echocardiography showed left ventricle apical obliteration and a restrictive pattern. Pulmonary angiography demonstrated a thrombus in the lingular and middle lobe. Despite treatment, the patient deceased seven days after admission. Autopsy confirmed the diagnosis of Loffler endocarditis. PMID- 26904306 TI - Midventricular Hypertrophic Cardiomyopathy with Apical Aneurysm: Potential for Underdiagnosis and Value of Multimodality Imaging. AB - We illustrate a case of midventricle obstructive HCM and apical aneurysm diagnosed with appropriate use of multimodality imaging. A 75-year-old African American woman presented with a 3-day history of chest pain and dyspnea with elevated troponins. Her electrocardiogram showed sinus rhythm, left atrial enlargement, left ventricular hypertrophy, prolonged QT, and occasional ectopy. After medical therapy optimization, she underwent coronary angiography for an initial diagnosis of non-ST segment elevation myocardial infarction. Her coronaries were unremarkable for significant disease but her left ventriculogram showed hyperdynamic contractility of the midportion of the ventricle along with a large dyskinetic aneurysmal apical sac. A subsequent transthoracic echocardiogram provided poor visualization of the apical region of the ventricle but contrast enhancement identified an aneurysmal pouch distal to the midventricular obstruction. To further clarify the diagnosis, cardiac magnetic resonance imaging with contrast was performed confirming the diagnosis of midventricular hypertrophic cardiomyopathy with apical aneurysm and fibrosis consistent with apical scar on delayed enhancement. The patient was medically treated and subsequently underwent elective implantable defibrillator placement in the ensuing months for recurrent nonsustained ventricular tachycardia and was initiated on prophylactic oral anticoagulation with warfarin for thromboembolic risk reduction. PMID- 26904307 TI - Beta Lactamase Producing Clostridium perfringens Bacteremia in an Elderly Man with Acute Pancreatitis. AB - Clostridium perfringens bacteremia is associated with adverse outcomes. Known risk factors include chronic kidney disease, malignancy, diabetes mellitus, and gastrointestinal disease. We present a 74-year-old man admitted with confusion, vomiting, and abdominal pain. Exam revealed tachycardia, hypotension, lethargy, distended abdomen, and cold extremities. He required intubation and aggressive resuscitation for septic shock. Laboratory data showed leukocytosis, metabolic acidosis, acute kidney injury, and elevated lipase. CT scan of abdomen revealed acute pancreatitis and small bowel ileus. He was started on vancomycin and piperacillin-tazobactam. Initial blood cultures were positive for C. perfringens on day five. Metronidazole and clindamycin were added to the regimen. Repeat CT (day 7) revealed pancreatic necrosis. The patient developed profound circulatory shock requiring multiple vasopressors, renal failure requiring dialysis, and bacteremia with vancomycin-resistant enterococci. Hemodynamic instability precluded surgical intervention and he succumbed to multiorgan failure. Interestingly, our isolate was beta lactamase producing. We review the epidemiology, risk factors, presentation, and management of C. perfringens bacteremia. This case indicates a need for high clinical suspicion for clostridial sepsis and that extended spectrum beta lactam antibiotic coverage may be inadequate and should be supplemented with use of clindamycin or metronidazole if culture is positive, until sensitivities are known. PMID- 26904308 TI - Identification Bracelet Precipitated Acute Compartment Syndrome during Intravenous Infusion in an Obtunded Patient. AB - Acute compartment syndrome is a serious condition requiring immediate medical care. A lack of urgent medical treatment can result in serious complications such as loss of function and even amputation. While the pathophysiology of acute compartment syndrome is well understood, numerous potential causes are still being discovered. A rare cause of acute compartment syndrome is IV infiltration. We present a case of acute compartment syndrome resulting from intravenous infusion due to proximal placement of a patient identification bracelet. We conclude that both routine evaluation for IV infiltration and proximal placement of IV lines are essential for prevention of acute compartment syndrome. PMID- 26904309 TI - DRESS Syndrome in the ICU: When a Patient Is Treated with Multiple Drugs. AB - The Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome is life-threatening. It associates a skin condition with hematological and visceral disorders. The DRESS syndrome diagnosis in the intensive care unit (ICU) is difficult as clinical features are nonspecific. Furthermore, the need to treat patients with multiple drugs usually prevents the identification of the causative drug. We report the case of a patient who developed two bouts of DRESS caused by piperacillin-tazobactam, the first being complicated with a distributive shock. Cases of DRESS occurring inside ICU are seldom reported. However, any intensivist may encounter this situation during his career and should be aware of its diagnostic and management specific aspects. PMID- 26904310 TI - Cone Beam Computed Tomographic Evaluation and Diagnosis of Mandibular First Molar with 6 Canals. AB - Root canal treatment of tooth with aberrant root canal morphology is very challenging. So thorough knowledge of both the external and internal anatomy of teeth is an important aspect of root canal treatment. With the advancement in technology it is imperative to use modern diagnostic tools such as magnification devices, CBCT, microscopes, and RVG to confirm the presence of these aberrant configurations. However, in everyday endodontic practice, clinicians have to treat teeth with atypical configurations for root canal treatment to be successful. This case report presents the management of a mandibular first molar with six root canals, four in mesial and two in distal root, and also emphasizes the use and importance of Cone Beam Computed Tomography (CBCT) as a diagnostic tool in endodontics. PMID- 26904311 TI - Breaking the Thumb Sucking Habit: When Compliance Is Essential. AB - The anterior open bite (AOB) and posterior cross bite are the most frequent malocclusions associated with prolonged sucking habits. This clinical case illustrates and discusses the use of a Haas-type palatal expander for stopping a thumb sucking habit. The improvement in closing the open bite with discontinuation of the habit was observed. But with the return of the habit and lack of cooperation, the relapse of anterior open bite occurred. Therefore, different approaches are necessary. The need of a multidisciplinary approach, consent, and cooperation are keys to a good prognosis. PMID- 26904302 TI - Impaired Functional Connectivity in the Prefrontal Cortex: A Mechanism for Chronic Stress-Induced Neuropsychiatric Disorders. AB - Chronic stress-related psychiatric diseases, such as major depression, posttraumatic stress disorder, and schizophrenia, are characterized by a maladaptive organization of behavioral responses that strongly affect the well being of patients. Current evidence suggests that a functional impairment of the prefrontal cortex (PFC) is implicated in the pathophysiology of these diseases. Therefore, chronic stress may impair PFC functions required for the adaptive orchestration of behavioral responses. In the present review, we integrate evidence obtained from cognitive neuroscience with neurophysiological research with animal models, to put forward a hypothesis that addresses stress-induced behavioral dysfunctions observed in stress-related neuropsychiatric disorders. We propose that chronic stress impairs mechanisms involved in neuronal functional connectivity in the PFC that are required for the formation of adaptive representations for the execution of adaptive behavioral responses. These considerations could be particularly relevant for understanding the pathophysiology of chronic stress-related neuropsychiatric disorders. PMID- 26904313 TI - Management of Horizontal Root Fracture in the Middle Third via Intraradicular Splinting Using a Fiber Post. AB - Radicular fractures in permanent teeth are uncommon injuries and account for only 0.5-7% of dental traumas. These fractures commonly result from a horizontal impact and are transverse to oblique in direction. Their incidence is more in the middle third of the root than at the apical and cervical thirds. This paper describes a case of complicated crown fracture of maxillary incisors along with horizontal root fracture at the middle third of maxillary right central and lateral incisor. The fractured root fragments of the upper right central and lateral incisor were united with the help of a glass fiber post after receiving an endodontic treatment. The other two incisors were treated endodontically followed by post endodontic restorations. Eventually the four incisors were restored with porcelain fused to metal crowns. A one-year follow-up revealed a well stabilized assembly of the root fragments and the post. PMID- 26904312 TI - Nasolabial Cyst Associated with Odontogenic Infection. AB - The nasolabial cyst or Klestadt cyst is a relatively uncommon nonodontogenic cyst that develops in the nasal alar region; it has uncertain pathogenesis. This lesion has slow growth and variable dimensions and is characterized clinically by a floating tumefaction in the nasolabial fold area around the bridge of the nose, causing an elevation of the upper lip and relative facial asymmetry. Diagnosis is primarily made clinically; if necessary, this is complemented by imaging. This paper reports the case of a 39-year-old male patient who complained of pain in the right upper premolar region and poor aesthetics due to a firm tumor in the right wing of the nose. Initially, this was thought to be due to an odontogenic abscess; however, the differential diagnosis was that a nasolabial cyst was communicating with the apex of teeth 14 and 15. Surgical treatment was carried out, followed by histopathological examination and concomitant endodontic treatment of the teeth involved. PMID- 26904314 TI - The Great Imitator Strikes Again: Syphilis Presenting as "Tongue Changing Colors". AB - Syphilis is known as the great imitator, making its diagnosis in the emergency department difficult. A 29-year-old male presented with the chief complaint of "my tongue is changing colors." A syphilis rapid plasma reagin (RPR) test resulted as positive. In primary syphilis, the chancre is the characteristic lesion. While chancres are frequently found on the external genitalia or anus, extragenital chancres arise in 2% of patients. With oral involvement, the chancre is commonly found on the lip or tongue. The patient was treated for secondary syphilis with 2.4 million units of long acting penicillin intramuscularly. On follow-up a month later, the patient's symptoms had resolved. PMID- 26904315 TI - A Tuboovarian Abscess Associated with a Ruptured Spleen. AB - We report the first case of a tuboovarian abscess complicated by a ruptured spleen. Our patient was a 27-year-old female with human immunodeficiency virus (HIV) who presented to the emergency department (ED) with complaints of urinary symptoms and diarrhea. After being diagnosed with a tuboovarian abscess (TOA), she received antibiotics and was admitted to the gynecology service. Shortly thereafter she developed hemorrhagic shock, necessitating a splenectomy and salpingooophorectomy from a ruptured spleen. PMID- 26904317 TI - Pseudohypoaldosteronism in a Neonate Presenting as Life-Threatening Hyperkalemia. AB - Context. Pseudohypoaldosteronism type 1 (PHA1) is a life-threatening disease that causes severe hyperkalemia and cardiac arrest if not treated appropriately or if diagnosis is missed. Objective. To report a case of a newborn with vomiting and lethargy, ultimately diagnosed with pseudohypoaldosteronism. Patient. This case presented to the ED at an age of 14 days in hypovolemic shock. There was a family history of sudden infant death, her sister who was diagnosed with CAH and passed away at 3 months of age despite regular hormone replacement. Our patient had cardiac arrest in ED, due to hyperkalemia; while receiving fluid boluses, cardiopulmonary resuscitation was initiated. After stabilization, diagnostic workup demonstrated persistently low sodium, acidosis, and high potassium, which required peritoneal dialysis. Based on these findings, the patient was diagnosed with CAH. It turned out later that the patient had PHA1. Two years later, the patient had a new sibling with the same disease diagnosed at birth and started immediately on treatment without any complication. Conclusions and Outcome. This case highlights the significant diagnostic and therapeutic challenges in treating children with PHA1. Adrenal crisis is not always CAH; delayed diagnosis can lead to complication and even death. The presence of high plasma renin activity, aldosterone, and cortisol, along with the presence of hyponatremia and hyperkalemia, established the diagnosis of PHA type 1 and ruled out CAH. PMID- 26904316 TI - An Ectopic ACTH Secreting Metastatic Parotid Tumour. AB - A 60-year old woman presented with features of Cushing's syndrome (CS) secondary to an ectopic adrenocorticotropic hormone (ACTH) secreting metastatic parotid tumour 3 years after excision of the original tumour. She subsequently developed fatal intestinal perforation and unfortunately died despite best possible medical measures. Ectopic ACTH secretion accounts for 5-10% of all patients presenting with ACTH dependent hypercortisolism; small cell carcinoma of lung (SCLC) and neuroendocrine tumours (NET) account for the majority of such cases. Although there are 4 previous case reports of ectopic ACTH secreting salivary tumours in literature, to our knowledge this is the first published case report in which the CS developed after 3 years of what was deemed as a successful surgical excision of primary salivary tumour. Our patient initially had nonspecific symptoms which may have contributed to a delay in diagnosis. Perforation of sigmoid colon is a recognised though underdiagnosed complication associated with steroid therapy and hypercortisolism. This case demonstrates the challenges faced in diagnosis as well as management of patients with CS apart from the practical difficulties faced while trying to identify source of ectopic ACTH. PMID- 26904318 TI - DKA with Severe Hypertriglyceridemia and Cerebral Edema in an Adolescent Boy: A Case Study and Review of the Literature. AB - A 13-year-old adolescent boy with type 1 diabetes mellitus (1b) presented with diabetic ketoacidosis (DKA) and cerebral edema. Grossly lipemic serum and lipemia retinals due to extremely high triglyceride (TG) level were observed without evidence of xanthoma or xanthelasma. Cerebral edema was treated by appropriate ventilation and mannitol administration. Normal saline was carefully given and regular insulin was titrated according to blood sugar levels. Triglyceride levels were reduced from 9,800 mg/dL to normal range within 9 days after conventional treatment was commenced without antilipid medication. Based on our review of the literature, this is the first reported case of confirmed pediatric DKA with severe hypertriglyceridemia and cerebral edema. In patients with DKA and hypertriglyceridemia, clinicians should be mindful of the possibility of associated acute pancreatitis and cerebral edema. PMID- 26904319 TI - A Timely Intervention: Endoscopic Retrieval of a Swallowed Magnetized Activity Watch. AB - The accidental ingestion of a foreign object often presents a difficult scenario for the clinician. This includes not only the decision to retrieve the material but also the appropriate technique to use. We present the case of a young asymptomatic girl who swallowed a magnetic activity watch, which was then successfully retrieved with an endoscopic snare. To our knowledge, this is the first documented case of salvaging an operational watch from the stomach using an endoscopic technique. PMID- 26904320 TI - Osteoporosis-Pseudoglioma in a Mauritanian Child due to a Novel Mutation in LRP5. AB - Osteoporosis-pseudoglioma (OPPG) syndrome is a very rare autosomal recessive disorder, caused by mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene. It manifests by severe juvenile osteoporosis with congenital or infancy-onset visual loss. We describe a case of OPPG due to novel mutation in LRP5 gene, occurring in a female Mauritanian child. This 10-year-old female child was born blind, and after then multiple fragility fractures appeared. PCR amplification and sequencing revealed a novel homozygous nonsense mutation in exon 10 of the LRP5 gene (c.2270G>A; pTrP757(*)); this mutation leads to the production of a truncated protein containing 757 amino acids instead of 1615, located in the third beta-propeller domain of the LRP5 protein. Both parents were heterozygous for the mutation. This is the first case of the OPPG described in black Africans, which broadens the spectrum of LRP5 gene mutations in OPPG. PMID- 26904321 TI - T Cell/Histiocyte-Rich Large B Cell Lymphoma of the Thymus: A Diagnostic Pitfall. AB - T cell/histiocyte-rich large B cell lymphoma (THRLBCL) is predominantly a nodal disease, with extranodal involvement, such as bone marrow, spleen, and liver. However, primary THRLBCL has never been reported in the thymus in the English literature. Here we report a case of THRLBCL presenting as mediastinal mass and lymphadenopathy. Based on the frozen section diagnosis of "thymoma," a 12 cm mass was excised. A year later she developed multiple enlarged lymph nodes and pulmonary nodules. Consultant review of the excised mediastinal mass showed scattered large atypical cells that were CD20+ and PAX-5+ and negative for pan cytokeratin, AE1, and AE3, compatible with THRLBCL and excluding thymoma. The excised lymph nodes were replaced by diffuse infiltrate of small CD3+ lymphocytes and histiocytes with intermingled large CD20+ B lymphoma cells scattered throughout the section. A diagnosis of THRLBCL was made in lymph node, similar to previous thymic lesion. A clonal rearrangement of immunoglobulin heavy chain (IGH) gene was detected, further supporting the diagnosis. This is the first reported case of THRLBCL in thymus. Correct recognition of this entity is critical, because of the difference in therapeutic impact on these patients. PMID- 26904322 TI - Acute Lymphoblastic Leukemia Arising in CALR Mutated Essential Thrombocythemia. AB - The development of acute lymphoblastic leukemia in an existing myeloproliferative neoplasm is rare with historical cases unable to differentiate between concomitant malignancies or leukemic transformation. Molecular studies of coexisting JAK2 V617F-positive myeloproliferative neoplasms and mature B cell malignancies indicate distinct disease entities arising in myeloid and lymphoid committed hematopoietic progenitor cells, respectively. Mutations of CALR in essential thrombocythemia appear to be associated with a distinct phenotype and a lower risk of thrombosis yet their impact on disease progression is less well defined. The as yet undescribed scenario of pro-B cell acute lymphoblastic leukemia arising in CALR mutated essential thrombocythemia is presented. Intensive treatment for the leukemia allowed for expansion of the original CALR mutated clone. Whether CALR mutations in myeloproliferative neoplasms predispose to the acquisition of additional malignancies, particularly lymphoproliferative disorders, is not yet known. PMID- 26904324 TI - Laparoscopic Resection of Cholecystocolic Fistula and Subtotal Cholecystectomy by Tri-Staple in a Type V Mirizzi Syndrome. AB - The Mirizzi syndrome (MS) is an impacted stone in the cystic duct or Hartmann's pouch that mechanically obstructs the common bile duct (CBD). We would like to report laparoscopic subtotal cholecystectomy (SC) and resection of cholecystocolic fistula by the help of Tri-StapleTM in a case with type V MS and cholecystocolic fistula, for first time in the literature. A 24-year-old man was admitted to emergency department with the complaint of abdominal pain, intermittent fever, jaundice, and diarrhea. Two months ago with the same complaint, ERCP was performed. Laparoscopic resection of cholecystocolic fistula and subtotal cholecystectomy were performed by the help of Tri-Staple. At the eight-month follow-up, he was symptom-free with normal liver function tests. In a patient with type V MS and cholecystocolic fistula, laparoscopic resection of cholecystocolic fistula and SC can be performed by using Tri-Staple safely. PMID- 26904323 TI - Higher Risk Myelodysplastic Syndromes in Patients with Well-Controlled HIV Infection: Clinical Features, Treatment, and Outcome. AB - Introduction. In advanced HIV prior to combination antiretroviral therapy (ART), dysplastic marrow changes occurred and resolved with ART. Few reports of myelodysplastic syndromes (MDS) in well-controlled HIV exist and management is undefined. Methods. Patients with well-controlled HIV and higher risk MDS were identified; characteristics, treatment, and outcomes were reviewed. Results. Of 292 MDS patients since 1996, 1 (0.3%) was HIV-positive. A 56-year-old woman presented with cytopenias. CD4 was 1310 cells/mL and HIV viral load <40 copies/mL. Bone marrow biopsy showed RCMD and karyotype included del(5q) and del(7q); IPSS was intermediate-2 risk. She received azacitidine at 75% dose. Cycle 2, at full dose, was complicated by marrow aplasia and possible AML; she elected palliation. Three additional HIV patients with higher risk MDS, aged 56 64, were identified from the literature. All had deletions involving chromosomes 5 and 7. MDS treatment of 2 was not reported and one received palliation; all died of AML. Conclusion. Four higher risk MDS in well-controlled HIV were below the median age of diagnosis for HIV-negative patients; all had adverse karyotype. This is the first report of an HIV patient receiving MDS treatment with azacitidine. Cytopenias were profound and dosing in HIV patients should be considered with caution. PMID- 26904325 TI - Streptococcus agalactiae Meningitis in Adult Patient: A Case Report and Literature Review. AB - We report a case of group B streptococcus meningitis in a 72-year-old female patient who was admitted in our hospital with a 21-day history of bilateral lower thigh pain and swelling associated with fever, headache, and vomiting. Her past medical history was remarkable for DM type 2, hypertension, and hypothyroidism. Upon admission, examination showed bilateral warmth and tender soft tissue swelling around the knees and MRI showed cellulitis of distal thirds of both thighs. The next day, the patient became drowsy. Neurologic examination showed neck rigidity and right sided hemiparesis. Cerebrospinal fluid and blood cultures yielded group B streptococcus sensitive to ceftriaxone, penicillin G, and vancomycin. The patient received ceftriaxone for a total of 14 days after which she improved and was discharged from the hospital with right sided weakness. PMID- 26904326 TI - Risk Factors and Epidemiology of Coccidioidomycosis Demonstrated by a Case of Spontaneous Pulmonary Rupture of Cavitary Coccidioidomycosis. AB - A 31-year-old Hispanic male with no medical history was admitted for fevers, pleurisy, and cough after recent oral surgery and completing demolition and construction work in Juarez, Mexico. Imaging showed a 4.4 cm cavitary lesion and bilateral tree-in-bud opacities. Initial suspicion of bacterial infection confirmed with clinical improvement on culture specific antibiotics, but after discharge he returned with progression of symptoms and new dyspnea. Radiograph showed a pyopneumothorax. Chest computed tomography after thoracostomy showed worsening infiltrates and another cavitary lesion. Symptoms persisted despite addition of broad spectrum antibiotics. Surgical repair for persistent air leak was required. Weeks after discharge, cultures and serologies returned positive for Coccidioidomycosis immitis. Coccidioides species cause up to 30% of community acquired pneumonia and incidental cavitary lesions in endemic regions. Symptoms are nonspecific yet usually involve fatigue, cough, and pleurisy. Most hosts have spontaneous resolution; however, certain demographics such as Hispanics and diabetics, later diagnosed in our patient, have higher morbidity. As seen with our patient, cavitary rupture and bronchopleural fistulas are rare occurring in 2.6% of cavitary lesions. High suspicion based on symptoms and host demographics is important to assist in early diagnosis and treatment to avoid and treat this common pathogen's presentations. PMID- 26904327 TI - Granulomatous Interstitial Nephritis Presenting as Hypercalcemia and Nephrolithiasis. AB - We report a case of acute kidney injury as the initial manifestation of sarcoidosis. A 55-year-old male was sent from his primary care physician's office with incidental lab findings significant for hypercalcemia and acute kidney injury with past medical history significant for nephrolithiasis. Initial treatment with intravenous hydration did not improve his condition. The renal biopsy subsequently revealed granulomatous interstitial nephritis (GIN). Treatment with the appropriate dose of glucocorticoids improved both the hypercalcemia and renal function. Our case demonstrates that renal limited GIN due to sarcoidosis, although a rare entity, can cause severe acute kidney injury and progressive renal failure unless promptly diagnosed and treated. PMID- 26904329 TI - Optic Nerve Sheath Meningioma Masquerading as Optic Neuritis. AB - Optic neuritis is a common presentation of demyelinating disorders such as multiple sclerosis. It typically presents with acute painful monocular vision loss, whereas chronic optic neuropathy can be caused by compressive lesions along the anterior visual pathway, genetic, toxic, or nutritional causes. We report an unusual presentation mimicking optic neuritis, which was subsequently diagnosed as optic nerve sheath meningioma (ONSM). Misinterpretation of white matter lesions on MRI of brain and the failure to image the optic nerves at the time of acute loss of vision led to the misdiagnosis of optic neuritis in this case. A comprehensive accurate history and ordering the appropriate imaging modality remain paramount in diagnosing progressive visual deterioration. PMID- 26904328 TI - Chronic Encapsulated Expanding Thalamic Hematoma Associated with Obstructive Hydrocephalus following Radiosurgery for a Cerebral Arteriovenous Malformation: A Case Report and Literature Review. AB - Chronic encapsulated intracerebral hematoma is a unique type of intracerebral hematoma accompanied by a capsule that is abundant in fragile microvasculature occasionally causing delayed regrowth. A 37-year-old man who had undergone radiosurgery for an arteriovenous malformation (AVM) causing intracerebral hematoma in the left parietal lobe presented with headache, vomiting, and progressive truncal ataxia due to a cystic lesion that had been noted in the left thalamus, leading to progressive obstructive hydrocephalus. He underwent left frontal craniotomy via a transsylvian fissure approach, and the serous hematoma was aspirated. The hematoma capsule was easy to drain and was partially removed. Pathological findings demonstrated angiomatous fibroblastic granulation tissue with extensive macrophage invasion. The concentration of vascular endothelial growth factor (VEGF) was high in the hematoma (12012 pg/mL). The etiology and pathogenesis of encapsulated hematoma are unclear, but the gross appearance and pathological findings are similar to those of chronic subdural hematoma. Based on the high concentration of VEGF in the hematoma, expansion of the encapsulated hematoma might have been caused by the promotion of vascular permeability of newly formed microvasculature in the capsule. PMID- 26904330 TI - Essure Surgical Removal and Subsequent Resolution of Chronic Pelvic Pain: A Case Report and Review of the Literature. AB - Background. Hysteroscopic tubal sterilization (Essure) is a minimally invasive option for permanent contraception with high reported rates of patient satisfaction. A small percentage of these women subsequently choose to have the tubal inserts removed due to regret or perceived side effects such as late-onset pelvic pain secondary to placement of the Essure device. Case. A twenty-nine-year old woman G4P4014 presented with a two-year complaint of chronic pelvic pain and dyspareunia after the hysteroscopic placement of an Essure device for sterilization. On reviewing the images of the HSG, it was noted that although tubal occlusion was confirmed, the left Essure coil appeared curved on itself in an elliptical fashion and did not seem to follow the expected anatomic trajectory of the fallopian tube. The patient reported resolution of chronic pelvic pain following laparoscopic removal of Essure device. Conclusion. A misplaced Essure device should be considered in the differential diagnosis of chronic pelvic pain in women who had difficult placement of the device. In addition to demonstrating tubal occlusion, careful examination of the configuration of the Essure microinserts on HSG examination provides valuable information in patients with pelvic pain after Essure placement. PMID- 26904331 TI - Prenatal Ultrasound Diagnosis of a Cyst of the Oral Cavity: An Unusual Case of Thyroglossal Duct Cyst Located on the Tongue Base. AB - We describe a case of a lingual thyroglossal duct cyst diagnosed prenatally by ultrasound at 26 weeks of gestation. The follow-up ultrasound scans revealed no changes in the cyst measurement. Surgical treatment was performed without any complication 72 hours after delivery with good results. PMID- 26904332 TI - Myxoid Chondrosarcoma of Maxilla in a Pediatric Patient: A Rare Case Report. AB - Myxoid variant of chondrosarcoma is an uncommon potentially lethal malignant tumor which is even rare in pediatric age group. In the present paper, we report one such case of intermediate grade myxoid chondrosarcoma of left side of maxilla in a 12-year-old girl. The present case had a firm, painless, and lobulated growth in premolar-molar region which was associated with bicortical expansion. Maxillofacial imaging showed ill-defined radiolucency with displaced maxillary molars. Osteolytic changes were evident with the alveolus and walls of maxillary sinus. Owing to the age of the patient, surgical excision was selected as the modality of management followed by postoperative radiotherapy. This report encompasses the entire gamut of clinicopathological, radiological, and treatment modalities employed for chondrosarcoma. PMID- 26904333 TI - Pulmonary Fibrosis after Pegylated Liposomal Doxorubicin in Elderly Patient with Cutaneous Angiosarcoma. AB - Introduction. Angiosarcoma is a rare cancer of the inner lining of blood vessels and can arise anywhere in the body, most commonly presenting as cutaneous disease in elderly patient, involving head and neck (H&N), especially the scalp. Pegylated liposomal doxorubicin (PLD) is one of the available treatments in patients with advanced or metastatic disease. Common toxicities are myelosuppression, palmar-plantar erythrodysesthesia, nausea, and stomatitis. Regarding PLD-related pulmonary fibrosis in an uncommon toxicity, there are few cases reported in literature. None of these occurred in angiosarcoma. Methods. This is a case report describing an elderly patient treated with PLD for advanced H&N cutaneous angiosarcoma who developed G5 pulmonary toxicity after the second PLD administration. Results. According to our data and patient clinical outcome, we believe that she passed away from fatal PLD-induced pulmonary fibrosis. This is the first case of fatal interstitial pneumonitis in a 77-year-old woman treated with PLD for angiosarcoma. The case has been reported for its rarity. Conclusions. Pathophysiology of this phenomenon is still unclear and more studies are necessary to understand the true incidence of pulmonary toxicities in patients in treatments with PLD and its mechanism. PMID- 26904334 TI - Free-Floating Iris Pigmented Epithelial Cyst in the Anterior Chamber. AB - An unusual case of a free-floating peripheral pigmented cyst in the anterior chamber is presented. A 30-year-old Caucasian male presented reporting a visual defect on his right eye in prone position over the past year. Slit-lamp examination revealed a small pigmented free-floating peripheral iris cyst at the 6 o'clock position in the anterior chamber. Ultrasound biomicroscopy revealed an unfixed epithelial pigmented cyst with an extremely thin wall and no internal reflectivity. Due to the lack of severity of visual disturbance of the patient, no surgical treatment was indicated. The patient is to be followed up annually and advised to return immediately in case of pain or any visual symptoms. Free floating iris cysts in the anterior chamber are uncommon and remain stable in the majority of cases. Management includes only regular observation until any complications arise. PMID- 26904335 TI - Bilateral One-Stage Revision of Infected Total Hip Arthroplasties: Report of Two Cases and Management of Antibiotic Therapy. AB - Recommendations for the management of chronic and bilateral total hip arthroplasty (THA) infection are lacking. However, this type of infection involves medical problems concerning the management of the antibiotic therapy. We report two cases of such infections operated as one-stage revision. For each case, both hips were infected with the same bacteria (Staphylococcus caprae for one patient and methicillin-sensitive Staphylococcus aureus for the other). The probabilistic antibiotic treatment started during the first side (after harvesting intraoperative samples) did not prevent the culture of the bacteriologic harvested during the intervention of the second side. Cultures were positive for the same bacteria for both sides in the two cases presented herein. After results of intraoperative cultures, patients received culture-guided antibiotic therapy for three months and were considered cured at the end of a two year follow-up. Our results suggest one-stage bilateral change of infected THA is a viable option and that early intraoperative antibiotic, started during the first-side exchange, does not jeopardize microbiological documentation of the second side. This work brings indirect arguments, in favor of the use of prophylactic antibiotics during revision of infected THA. PMID- 26904336 TI - A Posteriorly Displaced Distal Metaphyseal Clavicular Fracture (Type IV AC Joint Dislocation-Like) in Children: A Case Report and Literature Review Study. AB - Fractures of the lateral end of the clavicle are common in pediatric patients; most of these fractures occur at the physeal level representing Salter Harris injuries. The vast majority of fractures of the lateral end of the clavicle are managed nonoperatively. In this report, we describe a unique type of fracture of the distal end of the clavicle in the pediatric patients in which the fracture occurs in the metaphyseal lateral clavicle with the proximal edge of the fracture displaced posteriorly through the trapezius muscle causing obvious deformity. It is similar in pathology to type IV AC joint dislocation. In this study we report this injury in eleven-year-old boy. Literature review showed that similar injuries were described before three times (two of them in pediatric patients). Due to the significant clinical deformity of this category with entrapment of the bone through the trapezius muscle, reduction (open or closed) of the fracture is the recommended treatment. PMID- 26904338 TI - Facial Nerve Schwannoma of Parotid Gland: Difficulties in Diagnosis and Management. AB - Facial nerve schwannomas (FNS) are encapsulated benign tumors arising from Schwann cells of seventh cranial nerve. Most of the facial nerve schwannomas are localized in intratemporal region; only 9% of cases involve a portion of the extratemporal segment. Preoperative diagnosis is often unclear; diagnosis is often made intraoperatively. Management of intraparotid FNS is troublesome because of the facial nerve paralysis. In this report we presented a case of intraparotid schwannoma in a 55-year-old male patient complaining of a painless mass without peripheral facial nerve palsy in left parotid gland. Clinical features, preoperative and intraoperative diagnosis, and difficulties during management are discussed with the review of the literature. PMID- 26904337 TI - An Atraumatic Symphysiolysis with a Unilateral Injured Sacroiliac Joint in a Patient with Cushing's Disease: A Loss of Pelvic Stability Related to Ligamentous Insufficiency? AB - Glucocorticoids are well known for altering bone structure and elevating fracture risk. Nevertheless, there are very few reports on pelvic ring fractures, compared to other bones, especially with a predominantly ligamentous insufficiency, resulting in a rotationally unstable pelvic girdle. We report a 39-year-old premenopausal woman suffering from an atraumatic symphysiolysis and disruption of the left sacroiliac joint. She presented with external rotational pelvic instability and immobilization. Prior to the injury, she received high-dose glucocorticoids for a tentative diagnosis of rheumatoid arthritis over two months. This diagnosis was not confirmed. Other causes leading to the unstable pelvic girdle were excluded by several laboratory and radiological examinations. Elevated basal cortisol and adrenocorticotropic hormone levels were measured and subsequent corticotropin-releasing hormone stimulation, dexamethasone suppression test, and petrosal sinus sampling verified the diagnosis of adrenocorticotropic hormone-dependent Cushing's disease. The combination of adrenocorticotropic hormone-dependent Cushing's disease and the additional application of exogenous glucocorticoids is the most probable cause of a rare atraumatic rotational pelvic instability in a premenopausal patient. To the authors' knowledge, this case presents the first description of a rotationally unstable pelvic ring fracture involving a predominantly ligamentous insufficiency in the context of combined exogenous and endogenous glucocorticoid elevation. PMID- 26904339 TI - Sudden Sensorineural Hearing Loss after Orthopedic Surgery under Combined Spinal and Epidural Anesthesia. AB - Postoperative hearing loss following nonotologic surgery is rare. For patients undergoing subarachnoid anesthesia, the loss of cerebral spinal fluid and hence the drop in intracranial pressure can result in hearing loss and cranial nerve palsy. We report a case in which a patient sustained orthopedic surgery under combined spinal and epidural anesthesia complicated by severe and persistent sensorineural hearing loss. This report is a reminder that postoperative sudden sensorineural hearing loss is a poorly understood complication. A high index of suspicion is required for early diagnosis of this complication, although prompt treatment does not guarantee a good outcome. PMID- 26904340 TI - Pulmonary Empty Spaces: Silicone Embolism-A Decade of Increased Incidence and Its Histological Diagnosis. AB - Pulmonary embolism (PE) is a critical complication related to multiple disorders and different medical or cosmetic procedures. This case report presents two patients who were admitted for respiratory symptoms in the setting of previously receiving silicone injections for cosmetic purposes and were diagnosed with silicone pulmonary embolism. The relevance of including questions about all cosmetic procedures as a part of a medical history is highlighted, in particular about silicone injections. The diagnosis is confirmed by histological means. Additionally, our review showed the change of most common sites of silicone injections and a significant increase in cosmetic procedures causing silicone embolism during the past twelve years. PMID- 26904341 TI - A Rare Case of Esophageal Dysphagia in Children: Aberrant Right Subclavian Artery. AB - Dysphagia is an impairment of swallowing that may involve any structures from the mouth to the stomach. Esophageal dysphagia presents with the sensation of food sticking, pain with swallowing, substernal pressure, or chronic heartburn. There are many causes of esophageal dysphagia, such as motility disorders and mechanical and inflammatory diseases. Infrequently dysphagia arises from extrinsic compression of the esophagus from any vascular anomaly of the aortic arch. The most common embryologic abnormality of the aortic arch is aberrant right subclavian artery, clinically known as arteria lusoria. This abnormality is usually silent. Here, we report a case of six-year-old child presenting to us with a history of progressive dysphagia without respiratory symptoms. A barium esophagogram showed an increase of the physiological esophageal narrowing at the level of aortic arch, while at esophagogastroduodenoscopy there was an extrinsic pulsatile compression of the posterior portion of the esophagus suggesting an extrinsic compression by an aberrant vessel. Angio-CT (computed tomography) scan confirmed the presence of an aberrant right subclavian artery. PMID- 26904342 TI - Autoimmune Hemolytic Anemia and Hodgkin's Disease: An Unusual Pediatric Association. AB - Autoimmune hemolytic anemia (AIHA) is a recognized complication of lymphoproliferative disorders. AIHA associated with Hodgkin's disease (HD) is uncommon especially in the pediatric population. The diagnosis of AIHA is usually associated with HD at the time of initial presentation or during the course of disease, but it could precede it by years to months. In adults the association of AIHA and HD is more frequent in advanced stages and in the nodular sclerosis and mixed cellularity type HD. Warm immune hemolytic anemia is mainly controlled with steroids and chemotherapy. We report a case of a pediatric patient with direct antiglobulin positive test at the diagnosis of a late relapse of stage III B mixed cellularity type HD. PMID- 26904343 TI - Concomitant Use of Topiramate Inducing Neutropenia in a Schizophrenic Male Stabilized on Clozapine. AB - This is a case of a 23-year-old African American male with a history of paranoid schizophrenia that developed neutropenia on a clozapine-topiramate therapy. Clozapine had well addressed the patient's psychotic symptoms, while topiramate was used as a weight-lowering agent. The patient had fairly stable leukocyte counts for eight months on clozapine 300 mg and topiramate 100 mg daily. Doubling the dosage of topiramate led to severe neutropenia after two months. Reviewing the patient's laboratory reports showed a gradual decline of neutrophils occurring at a lower dosage, followed by a rapid decline after an increased dosage. In this case, we report that not only did topiramate act as the neutropenic agent, but also it might have done so in a dose-dependent manner. PMID- 26904344 TI - Pulmonary Embolism Originating from a Hepatic Hydatid Cyst Ruptured into the Inferior Vena Cava: CT and MRI Findings. AB - Pulmonary embolism due to hydatid cysts is a very rare clinical entity. Hydatid pulmonary embolism can be distinguished from other causes of pulmonary embolism with contrast-enhanced computed tomography (CECT) and magnetic resonance imaging (MRI). MRI especially displays the cystic nature of lesions better than CECT. Here we report a 45-year-old male patient with the pulmonary embolism due to ruptured hydatid liver cyst into the inferior vena cava. PMID- 26904345 TI - Bilateral Congenital Agenesis of the Long Head of the Biceps Tendon: The Beginning. AB - The biceps brachii muscle is prone to variants but absence of the long head of the biceps (LHB) tendon is an exceptionally rare anomaly. This report concerns the fourth case of bilateral congenital absence of the LHB tendon and presents the ultrasonography (US) and magnetic resonance (MR) findings. Our case has the peculiarity of being the first in which bilateral LHB tendon agenesis is not associated with rotator cuff or labral tears. PMID- 26904346 TI - Eosinophilic Esophagitis in Two Patients with Systemic Sclerosis. AB - The gastrointestinal tract (GIT) is the most common extracutaneous organ system damaged in systemic sclerosis (SSc) and is the presenting feature in 10% of patients. The esophagus as the portion of the GIT is the most commonly affected and there is an association of gastroesophageal reflux (GER) with SSc interstitial lung disease (ILD). Thus, an aggressive treatment for GER is recommended in all SSc patients with ILD; however, it is recognized that a long term benefit to this treatment is needed to understand its impact. In this case report we discuss the presence of eosinophilic esophagitis (EoE) in two SSc patients and discuss the role for early EGD in SSc patients with moderate-severe GER symptoms for tissue study. Assessment of esophageal biopsy specimens for the presence of eosinophils and possibly ANA can help elucidate disease pathogenesis and direct therapy, as the presence of EoE in SSc has important management considerations, particularly with regards to dietary modification strategies. PMID- 26904347 TI - Rheumatoid Arthritis, Kartagener's Syndrome, and Hyperprolactinemia: Who Started It? AB - We report a case of an 18-year-old girl who presented to our hospital with history of recurrent respiratory infections, amenorrhea, and symmetric polyarthritis. She was diagnosed with rheumatoid arthritis (RA), Kartagener's syndrome (KS), and hyperprolactinemia. There have been very few case reports in the literature of RA occurring in the setting of KS, theoretically proposed to be due to chronic stimulation of the immune system by recurrent infections. Furthermore, hyperprolactinemia has been hypothesized to mirror RA disease activity and case reports of treatment with dopamine agonists have led to the speculation of whether or not they represent a new line of experimental treatment in the future. Our patient was found to have both KS and hyperprolactinemia together in the setting of RA, and based on our literature search, this is the first reported case of such a combination. This strikes a very intriguing question: are these three conditions interlinked by a yet to be defined association? And treatment of which condition leads to the resolution of the other? PMID- 26904349 TI - Management of Urinary Incontinence in Complete Bladder Duplication by Injection of Bulking Agent at Bladder Neck Level into the Proximal Urethra. AB - Bladder duplication is a rare entity in children. The term encompasses a wide spectrum of anomalies from isolated bladder duplication in coronal or sagittal planes to duplicated bladder exstrophy and associated musculoskeletal and visceral anomalies. Given this wide variability, the treatment of these patients is not standardized. We hereby present a female patient with chief complaint of long-standing urinary incontinence who had complete bladder and urethral duplication and pubic diastasis. The patient was treated with bulking agent injection at the incompetent bladder neck and proximal urethra with resolution of incontinence, obviating the need for extensive surgeries. PMID- 26904348 TI - Double Incomplete Internal Biliary Fistula: Coexisting Cholecystogastric and Cholecystoduodenal Fistula. AB - Internal biliary fistula is a rare complication of a common surgical disease, cholelithiasis. It is seen in 0.74% of all biliary tract surgeries and is thought to be a result of repeated inflammatory periods of the gallbladder. In this report we present a case of incomplete cholecystogastric and cholecystoduodenal fistulae in a single patient missed by ultrasonography and endoscopic retrograde cholangiopancreatography and diagnosed intraoperatively. In the literature there is only one report of an incomplete cholecystogastric fistula. To our knowledge this is the first case of double incomplete internal biliary fistulae. PMID- 26904350 TI - Pure Laparoscopic Left Hemihepatectomy for Hepatic Peribiliary Cysts with Biliary Intraepithelial Neoplasia. AB - Introduction. Hepatic peribiliary cysts (HPCs) usually originate due to the cystic dilatation of the intrahepatic extramural peribiliary glands. We describe our rare experience of pure laparoscopic left hemihepatectomy (PLLH) in a patient with HPCs accompanied by a component of biliary intraepithelial neoplasia (BilIN). Case Presentation. A 65-year-old man was referred for further investigation of mild hepatic dysfunction. Contrast-enhanced computed tomography showed dilatation of the left-sided intrahepatic bile duct, and biliary cytology showed class III cells. The patient was highly suspected of having left side dominated cholangiocarcinoma and underwent PLLH. Microscopic findings revealed multiple cystic dilatations of the extramural peribiliary glands; hence, this lesion was diagnosed as HPCs. The resected intrahepatic bile duct showed that the normal ductal lumen comprised low columnar epithelia; however, front formation on the BilIN was observed in some parts of the intrahepatic bile duct, indicating that the BilIN coexisted with HPCs. Conclusion. We chose surgical therapy for this patient owing to the presence of some features of biliary malignancy. We employed noble PLLH as a minimally invasive procedure for this patient. PMID- 26904351 TI - Retracted: Adrenal Schwannomas: Rare Tumor of the Retroperitoneum. AB - [This retracts the article DOI: 10.1155/2015/547287.]. PMID- 26904352 TI - A Rare Case of the Simultaneous, Multifocal, Metastatic Renal Cell Carcinoma to the Ipsilateral Left Testes, Bladder, and Stomach. AB - We describe the rare case of a 68-year-old gentleman with the history of a hand assisted laparoscopic left radical nephrectomy for a T2bN0M1 clear cell renal cell carcinoma (RCC). Seven years after surgery and with clean surveillance imaging for metastasis/recurrence the patient presented with three separate tumors suspicious for malignancy. A bladder lesion was found during workup for hematuria, a stomach lesion during diagnostic endoscopy, and a testicular lesion during self-exam. He underwent transurethral resection of bladder tumor, left inguinal orchiectomy, and upper endoscopic ensnarement. All specimens surprisingly showed RCC by histology and immunostaining. These three sites are rare for RCC metastasis and simultaneous presentation is even rarer, further emphasizing the importance of continuous and careful follow-up in this patient population, despite what could appear as complete remission. PMID- 26904353 TI - Synchronous Renal Cell Carcinoma and Gastrointestinal Malignancies. AB - While renal cell carcinoma is the most commonly diagnosed neoplasm of the kidney, its simultaneous diagnosis with a gastrointestinal malignancy is a rare, but well reported phenomenon. This discussion focuses on three independent cases in which each patient was diagnosed with renal cell carcinoma and a unique synchronous gastrointestinal malignancy. Case 1 explores the diagnosis and surgical intervention of a 66-year-old male patient synchronously diagnosed with clear cell renal cell carcinoma and a carcinoid tumor of the small bowel. Case 2 describes the diagnosis and surgical intervention of a 61-year-old male found to have clear cell renal cell carcinoma and a mucinous appendiceal neoplasm. Lastly, Case 3 focuses on the interventions and management of a 36-year-old female diagnosed with synchronous clear cell renal carcinoma and hereditary nonpolyposis colorectal cancer. This case series examines each distinct patient's presentation, discusses the diagnosis, and compares and contrasts the findings while discussing the literature on this topic. PMID- 26904354 TI - Juxtarenal Modular Aortic Stent Graft Infection Caused by Staphylococcus aureus. AB - Introduction. We are presenting a case report of an infected modular abdominal stent graft. Case Presentation. A 67-year-old male patient three years after Cook's modular abdominal aortic aneurysm (AAA) graft implantation for juxtarenal AAA with an implantation of a stent extension into the right common iliac artery for type Ib endoleak. The patient was admitted into our center in severe condition with suspected retroperitoneal bleeding. Computed tomography angiography (CTAG) confirmed retroperitoneal bleeding in the right common iliac artery. An urgent surgical revision was indicated; destructed arterial wall around the stent extension in the right common iliac artery was discovered. Due to the severe state of health of the patient, a resection of the infected stent and affected arterial wall was performed, followed by an iliac-femoral crossover bypass. The patient was transported to the intensive care unit with hepatic and renal failure, with maximal catecholamine support. Combined antibiotic treatment was started. The patient died five hours after the procedure. The cause of death was multiorgan failure caused by sepsis. Hemocultures and perioperative microbiological cultures showed the infection agent to be Staphylococcus aureus methicillin sensitive. Conclusion. Stent graft infection is a rare complication. Treatment is associated with high mortality and morbidity. PMID- 26904355 TI - Correlates of Nine-Month Retention following Interim Buprenorphine-Naloxone Treatment in Opioid Dependence: A Pilot Study. AB - Interim medication-only treatment has been suggested for the initiation of opioid maintenance treatment (OMT) in opioid-dependent subjects, but this rarely has been studied using buprenorphine instead of methadone. Following a pilot trial assessing interim buprenorphine-naloxone treatment in order to facilitate transfer into OMT, we here aimed to study retention, and potential correlates of retention, in full-scale treatment. Thirty-six patients successfully referred from a waiting list through an interim treatment phase were followed for nine months in OMT. Baseline characteristics, as well as urine analyses during the interim phase and during full-scale OMT, were studied as potential correlates of retention. The nine-month retention in OMT was 83 percent (n = 30). While interim phase urine samples positive for benzodiazepines did not significantly predict dropout from full-scale OMT (p = 0.09), urine samples positive for benzodiazepines within full-scale OMT were significantly associated with dropout (p < 0.01), in contrast to other substances and baseline characteristics. Retention remained high through nine months in this pilot study sample of patients referred through buprenorphine-naloxone interim treatment, but use of benzodiazepines is problematic, and the present data suggest that it may be associated with treatment dropout. PMID- 26904356 TI - RyR2 QQ2958 Genotype and Risk of Malignant Ventricular Arrhythmias. AB - Ventricular arrhythmias are one of the most common causes of death in developed countries. The use of implantable cardiac defibrillators is the most effective treatment to prevent sudden cardiac death. To date, the ejection fraction is the only approved clinical variable used to determine suitability for defibrillator placement in subjects with heart failure. The purpose of this study was to assess whether genetic polymorphisms found in the ryanodine receptor type 2 (Q2958R) and histidine-rich calcium-binding protein (S96A) might serve as markers for arrhythmias. Genotyping was performed in 235 patients treated with defibrillator for primary and secondary prevention of arrhythmias. No significant association was found between the S96A polymorphism and arrhythmia onset, whereas the QQ2958 genotype in the ryanodine receptor gene was correlated with an increased risk of life-threatening arrhythmias. Concurrent stressor conditions, such as hypertension, seem to increase this effect. Our findings might help to better identify patients who could benefit from defibrillator implantation. PMID- 26904357 TI - Understanding Referral Patterns for Bone Mineral Density Testing among Family Physicians: A Qualitative Descriptive Study. AB - Introduction. Evidence of inappropriate bone mineral density (BMD) testing has been identified in terms of overtesting in low risk women and undertesting among patients at high risk. In light of these phenomena, the objective of this study was to understand the referral patterns for BMD testing among Ontario's family physicians (FPs). Methods. A qualitative descriptive approach was adopted. Twenty two FPs took part in a semi-structured interview lasting approximately 30 minutes. An inductive thematic analysis was performed on the transcribed data in order to understand the referral patterns for BMD testing. Results. We identified a lack of clarity about screening for osteoporosis with a tendency for baseline BMD testing in healthy, postmenopausal women and a lack of clarity on the appropriate age for screening for men in particular. A lack of clarity on appropriate intervals for follow-up testing was also described. Conclusions. These findings lend support to what has been documented at the population level suggesting a tendency among FPs to refer menopausal women (at low risk). Emphasis on referral of high-risk groups as well as men and further clarification and education on the appropriate intervals for follow-up testing is warranted. PMID- 26904358 TI - Variations in Incidence and Prevalence of Parkinson's Disease in Taiwan: A Population-Based Nationwide Study. AB - Demographic, socioeconomic, and urbanization level variations in Parkinson's disease (PD) are rarely investigated, especially in Asia. This study describes an eight-year trend in PD incidence and prevalence in Taiwan as well as assessing the effects of sociodemographics and urbanization on the incidence and prevalence of PD. The data analyzed were acquired from the Taiwan National Health Insurance Research Database (NHIRD) entries between 2002 and 2009. The calendar year, sex, and age-specific rates were standardized, and the effects of the sociodemographics and urbanization on PD were assessed using Poisson regression analysis. PD incidence and prevalence showed a significantly increasing trend, with a greater magnitude noted for prevalence than for incidence (87.3% versus 9.2%). The PD incidence and prevalence increased with age and were slightly higher in men than in women. The people who were not under the labor force (i.e., dependents) or with lower monthly incomes were at significantly increased adjusted incidence rate ratio (1.50-1.56) and adjusted prevalence rate ratio (1.66-1.71) of PD. Moreover, significantly higher PD incidence and prevalence were noted in areas with lesser urbanization. This information emphasizes the need for preventive and clinical care strategies targeting the segment of Taiwanese population that exhibited a greater incidence and prevalence of PD. PMID- 26904359 TI - Immunohistochemical Expression of Ki67 and p53 in Wilms Tumor and Its Relationship with Tumor Histology and Stage at Presentation. AB - Aim. Evaluate tumor proliferation marker (Ki67) and p53 tumor suppressor marker in Wilms tumor and correlate with histology, anaplasia, and staging. Design. Prospective, hospital based study conducted at a tertiary pediatric referral centre in south India. Setting. Wilms tumor is the most common childhood renal malignancy worldwide. Anaplasia on histology is associated with treatment resistance but not with aggressiveness clinical presentation. Chemotherapy for Wilms tumor is based on histology and staging. Most patients respond to current chemotherapy protocol. However, a small fraction relapses or metastasizes. Affordable prognostic markers are needed for histopathological evaluation of this tumor. Subjects. Cases of histologically confirmed Wilms tumor over five years. Cases after chemotherapy were excluded as the immunostaining was inconsistent in necrotic areas. Methods. The clinical and radiological findings of 31 cases of Wilms tumor were documented at a tertiary pediatric referral hospital over five years. In addition to Hematoxylin and Eosin staining, Ki67 proliferation index and p53 expression were correlated with tumor histology and staging. Results. Age incidence was 3-8 years with female preponderance. Significant correlation was noted between Ki67 proliferation index and tumor staging. p53 expression was not useful in stratification of Wilms tumor. Conclusion. Ki67 was cost-effective immunohistochemical marker for prognostication of pediatric Wilms tumor. PMID- 26904360 TI - Qualitative and Quantitative Analysis of Volatile Components of Zhengtian Pills Using Gas Chromatography Mass Spectrometry and Ultra-High Performance Liquid Chromatography. AB - Zhengtian pills (ZTPs) are traditional Chinese medicine (TCM) which have been commonly used to treat headaches. Volatile components of ZTPs extracted by ethyl acetate with an ultrasonic method were analyzed by gas chromatography mass spectrometry (GC-MS). Twenty-two components were identified, accounting for 78.884% of the total components of volatile oil. The three main volatile components including protocatechuic acid, ferulic acid, and ligustilide were simultaneously determined using ultra-high performance liquid chromatography coupled with diode array detection (UHPLC-DAD). Baseline separation was achieved on an XB-C18 column with linear gradient elution of methanol-0.2% acetic acid aqueous solution. The UHPLC-DAD method provided good linearity (R (2) >= 0.9992), precision (RSD < 3%), accuracy (100.68-102.69%), and robustness. The UHPLC-DAD/GC MS method was successfully utilized to analyze volatile components, protocatechuic acid, ferulic acid, and ligustilide, in 13 batches of ZTPs, which is suitable for discrimination and quality assessment of ZTPs. PMID- 26904361 TI - Prevention of Mother-to-Child Transmission of HIV/AIDS: Perception of Health Care Workers in Rural Areas of Oyo State. AB - Introduction. Proper implementation of prevention of mother-to-child transmission (PMTCT) services requires adequate knowledge and appropriate attitudes and practices on the part of the health care providers especially in rural areas where access to health care delivery is very limited in Oyo State. Materials and Methods. This is a descriptive cross-sectional survey of 350 health care workers in a two-stage sampling technique. Data was obtained using interviewer administered, pretested, semistructured questionnaires. The data was analyzed using Epi Info software version 7. Results. The knowledge of PMTCT of HIV was poor among the health care workers (69.1%). However, more than half (58.3%) had good attitudes towards PMTCT of HIV/AIDS. Predictors of good knowledge of PMTCT were religion [AOR = 1.6, 95% CI (1.1-2.6)], cadre of occupation [AOR = 10.2, 95% CI (2.9-35.1)], and length of service [AOR = 4.3, 95% CI (2.3-19.4)]. Predictors of good attitude towards PMTCT were length of service in the current hospital [AOR = 2.8, 95% CI (1.5-5.2)] and cadre of occupation [AOR = 3.9, 95% CI (1.28 11.9)]. Conclusion. Despite poor knowledge of PMTCT of HIV/AIDS among the health care workers, the attitude towards PMTCT of HIV/AIDS was good. There is need for the involvement of the stakeholders in bridging the gap between knowledge of and attitude towards prevention of MTCT of HIV/AIDS among health care workers in the rural areas. PMID- 26904362 TI - Serological Survey and Factors Associated with Toxoplasma gondii Infection in Domestic Goats in Myanmar. AB - Goat farming is important for the livelihood of millions of rural people because it contributes to food security and creation of assets. However, infection of goats with Toxoplasma gondii could be a source of parasite transmission to humans. The information on T. gondii infection of goat was not reported yet in Myanmar. A total of 119 goat serum samples were collected from three cities in the central region of Myanmar for T. gondii antibody survey. With the occurrence value obtained in this first study, a second one, more complete, with larger number (162) of animals and properties, was carried out and the risk factors and prevalence were determined. In both studies the samples were analyzed by the LAT. Of these, 32 (11.4%) samples were showed to be positive. The infection was associated with the presence of cats at the farm (odds ratio [OR] = 4.66, 95% confidential interval [CI] = 1.03-21.06), farming with different animal species (sheep, cattle, and pigs) (OR = 4.33, 95% CI = 1.57-11.94), and farming without good management practices (OR = 0.23, 95% CI = 0.06-0.83). This is the first T. gondii prevalence study in goats in the country. PMID- 26904363 TI - Symbiotic N 2 -Fixation Estimated by the (15) N Tracer Technique and Growth of Pueraria phaseoloides (Roxb.) Benth. Inoculated with Bradyrhizobium Strain in Field Conditions. AB - This field experiment was established in Eastern Cameroon to examine the effect of selected rhizobial inoculation on N2-fixation and growth of Pueraria phaseoloides. Treatments consisted of noninoculated and Bradyrhizobium yuanmingense S3-4-inoculated Pueraria with three replications each. Ipomoea batatas as a non-N2-fixing reference was interspersed in each Pueraria plot. All the twelve plots received 2 gN/m(2) of (15)N ammonium sulfate 10% atom excess. At harvest, dry matter yields and the nitrogen derived from atmospheric N2-fixation (%Ndfa) of inoculated Pueraria were significantly (P < 0.05) higher (81% and 10.83%, resp.) than those of noninoculated Pueraria. The inoculation enhanced nodule dry weight 2.44-fold. Consequently, the harvested N significantly (P < 0.05) increased by 83% in inoculated Pueraria, resulting from the increase in N2 fixation and soil N uptake. A loss of 55 to 60% of the N fertilizer was reported, and 36 to 40% of it was immobilized in soil. Here, we demonstrated that both N2 fixing potential of P. phaseoloides and soil N uptake are improved through field inoculations using efficient bradyrhizobial species. In practice, the inoculation contributes to maximize N input in soils by the cover crop's biomass and represent a good strategy to improve soil fertility for subsequent cultivation. PMID- 26904364 TI - In Vitro Cytotoxicity of Calcium Silicate-Based Endodontic Cement as Root-End Filling Materials. AB - The aim of this study was to evaluate the cytotoxicity of three types of calcium silicate-based endodontic cement after different incubation periods with human periodontal ligament fibroblasts. Human periodontal ligament fibroblasts were cultured from extracted third molars and seeded in 96-well plates. MTA, calcium enriched mixture (CEM) cement, and Biodentine were prepared and added to culture insert plates which were immediately placed into 96-well plates containing cultured cells. After incubation periods of 24, 48, and 72 hours, cell viability was determined with WST-1 assay. Data were analysed statistically by ANOVA with repeated measures and Bonferroni tests. There was no significant difference in cell viability amongst the test materials after each incubation period (P > 0.05). MTA and CEM presented more than 90% cell viability after 24 and 48 hours of incubation and showed statistically significant decrease in cell viability after 72 hours of incubation (P < 0.05). Biodentine showed significantly less cell viability (73%) after 24 hours of incubation, whereas more than 90% cell viability was seen after 48 and 72 hours of incubation (P < 0.05). Despite the significant changes in cell viability over time, materials presented similar cytotoxicity profile. Biodentine and CEM can be considered as alternative materials for root-end surgery procedures. PMID- 26904365 TI - Chronic hypertrophic nonunion of the Type II odontoid fracture causing cervical myelopathy: Case report and review of literature. AB - BACKGROUND: Complications of nonunited Type II odontoid fractures can range from neck pain to progressive neurological deficit from cervical myelopathy. Rarely, the hypertrophic nonunion requires both anterior transoral decompression and posterior decompression with instrumented fusion. We present a case and review literature around this entity. CASE DESCRIPTION: A 68-year-old female presented with rapidly progressive cervical myelopathy (from normal to moderate myelopathy modified Japanese Orthopedic Association [mJOA] 13) over 3 months. Her history was positive for a Type II odontoid fracture managed conservatively and lost to follow-up for 25 years. Spinal imaging studies revealed hypertrophic nonunion and craniocervical kyphotic deformity with significant subaxial stenosis and segmental kyphosis. The patient underwent anterior transoral decompression, followed by posterior occipitothoracic decompression and instrumented fusion. At follow-up, the cervical myelopathy has improved to near normalcy (mJOA 17) with no evidence or implant-related complication. CONCLUSION: Rarely, nonunion of Type II odontoid fractures may be hypertrophic where both instability and compression cause neurological morbidity. Such cases require anterior transoral decompression, posterior cervical decompression, and instrumented fusions. PMID- 26904366 TI - Spinal surgery: Who is in charge anyway? AB - BACKGROUND: More and more, no one seems to be in charge of taking care of patients with spinal disease both before and after spine surgery. Yet, as spine surgeons, we should not have to direct basic medical clearance prior to surgery, or direct basic medical postoperative care. METHODS: As we as spine surgeons did not complete medical residencies, why are we now being asked to take care of all postoperative issues in our patients undergoing spine surgery. As "captains of the ship," we are increasingly managing hypertension, diabetes, deep venous thrombosis/pulmonary embolism, and other basic medical issues. RESULTS: Although our medical colleagues perform the preoperative clearance, too frequently they are not involved in the patients' follow-up treatment. Often, our medical colleagues are nowhere to be found after surgery for any of the postoperative problems; therefore, "tag" we are it. Nevertheless, this should not be the case. CONCLUSIONS: So I ask again, who's in charge? Are we as spine surgeons now supposed to become the patients' primary care physicians, their pulmonologists, cardiologists, pain management specialists, much less their psychiatrists. Unfortunately, if we don't do this, no one else appears to be willing to step. PMID- 26904367 TI - Conservative management of a cervical ligamentum flavum hematoma: Case report. AB - BACKGROUND: Spontaneous epidural hematoma arising from the ligamentum flavum is a rare cause of acute spinal cord compression. There are only four reports in the cervical spine literature, and all were managed with surgery. Here, we describe an acute case of a spontaneous epidural hematoma arising from the ligamentum flavum in the cervical spine successfully managed without surgery. CASE DESCRIPTION: A 69-year-old woman with a cervical spine epidural hematoma contained within the ligamentum flavum presented with paroxysmal neck pain and stiffness without a history of trauma. The magnetic resonance imaging (MRI) revealed a posterolateral epidural hematoma contained within the ligamentum flavum. As the patient was intact, she was managed conservatively with cervical orthosis. Three months later, she was symptom-free, and the hematoma resolved on the follow-up MRI study. CONCLUSION: Spontaneous epidural hematoma arising from ligamentum flavum is a rare cause of spinal cord compression. Previous reports have described success with surgical decompression. However, initial observation and conservative management may be successful as illustrated in this case. PMID- 26904368 TI - Unusual brachial plexus lesion: Hematoma masquerading as a peripheral nerve sheath tumor. AB - BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) of the brachial plexus have unique radiographic and clinical findings. Patients often present with progressive upper extremity paresthesias, weakness, and pain. On magnetic resonance (MR) imaging, lesions are isointense on T1-weighted and hyperintense on T2-weighted sequences, while also demonstrating marked enhancement on MR studies with gadolinium diethylenetriamine pentaacetic acid. On the basis of their characteristic MR imaging features and rapid clinical progression, two brachial plexus lesions proved to be organizing hematomas rather than MPNST. METHODS: A 51 year-old male and a 31-year-old female were both assessed for persistent and worsened left-sided upper extremity pain, paresthesias, and weakness. In both cases, the MR imaging of the brachial plexus demonstrated an extraspinal enhancing lesion located within the left C7-T1 neuroforamina. RESULTS: Although the clinical and radiographic MR features for these 2 patients were consistent with MPNSTs, both lesions proved to be benign organizing hematomas. CONCLUSIONS: These two case studies emphasize that brachial plexus hematomas may mimic MPNSTs on MR studies. Accurate diagnosis of these lesions is critical for determining the appropriate management options and treatment plans. Delaying the treatment of a highly aggressive nerve sheath tumor can have devastating consequences, whereas many hematomas resolve without surgery. Therefore, if the patient has stable findings on neurological examination and a history of trauma, surgical intervention may be delayed in favor of repeat MR imaging in 2-3 months to re evaluate the size of the mass. PMID- 26904369 TI - Acquired dorsal intraspinal epidermoid cyst in an adult female. AB - BACKGROUND: Epidermoid and dermoid cyst comprise <1% of spinal tumors and may be congenital (hamartoma) or acquired (iatrogenic) in origin. Epidermoid cysts within the neuraxis are rare benign neoplasms that are most commonly located in the intracranial region. CASE DESCRIPTION: Here, we report the a case of an acquired intradural extramedullary epidermoid cyst involving the thoracic region in an adult female who had no associated history of an accompanying congenital spinal deformity. CONCLUSION: Early diagnosis and immediate surgical intervention reduce patient morbidity. Near complete or subtotal excision of the cyst wall is warranted to prevent inadvertent injury to the spinal cord thus minimizing neurological morbidity. PMID- 26904370 TI - Older literature review of increased risk of adjacent segment degeneration with instrumented lumbar fusions. AB - BACKGROUND: Adjacent segment degeneration (ASD) following lumbar spine surgery occurs in up to 30% of cases, and descriptions of such changes are not new. Here, we review some of the older literature concerning the rate of ASD, typically more severe cephalad than caudad, and highly correlated with instrumented fusions. Therefore, for degenerative lumbar disease without frank instability, ASD would be markedly reduced by avoiding instrumented fusions. METHODS: In a prior review, the newer literature regarding the frequency of ASD following lumbar instrumented fusions (e.g., transforaminal or posterior lumbar interbody fusions [TLIF/PLIF] fusions or occasionally, posterolateral fusions [PLFs]) was presented. Some studies cited an up to an 18.5% incidence of ASD following instrumented versus noninstrumented fusions/decompressions alone (5.6%). A review of the older literature similarly documents a higher rate of ASD following instrumented fusions performed for degenerative lumbar disease alone. RESULTS: More frequent and more severe ASD follows instrumented lumbar fusions performed for degenerative lumbar disease without instability. Alternatively, this entity should be treated with decompressions alone or with noninstrumented fusions, without the addition of instrumentation. CONCLUSIONS: Too many studies assume that TLIF, PLIF, and even PLF instrumented fusions are the "gold standard of care" for dealing with degenerative disease of the lumbar spine without documented instability. It is time to correct that assumption, and reassess the older literature along with the new to confirm that decompression alone and noninstrumented fusion avoid significant morbidity and even potentially mortality attributed to unnecessary instrumentation. PMID- 26904371 TI - Aulogous fibrin sealant (Vivostat((r))) in the neurosurgical practice: Part II: Vertebro-spinal procedures. AB - BACKGROUND: Epidural hematomas, cerebrospinal fluid fistula, and spinal infections are challenging postoperative complications following vertebro-spinal procedures. We report our preliminary results using autologous fibrin sealant as both fibrin glue and a hemostatic during these operations. METHODS: Prospectively, between January 2013 and March 2015, 68 patients received an autologous fibrin sealant prepared with the Vivostat((r)) system applied epidurally to provide hemostasis and to seal the dura. The surgical technique, time to bleeding control, and associated complications were recorded. RESULTS: Spinal procedures were performed in 68 patients utilizing autologous fibrin glue/Vivostat((r)) to provide rapid hemostasis and/or to seal the dura. Only 2 patients developed postoperative dural fistulas while none exhibited hemorrhages, allergic reactions, systemic complications, or infections. CONCLUSIONS: In this preliminary study, the application of autologous fibrin sealant with Vivostat((r)) resulted in rapid hemostasis and/or acted as an effective dural sealant. Although this product appears to be safe and effective, further investigations are warranted. PMID- 26904372 TI - More nerve root injuries occur with minimally invasive lumbar surgery, especially extreme lateral interbody fusion: A review. AB - BACKGROUND: In the lumbar spine, do more nerve root injuries occur utilizing minimally invasive surgery (MIS) techniques versus open lumbar procedures? To answer this question, we compared the frequency of nerve root injuries for multiple open versus MIS operations including diskectomy, laminectomy with/without fusion addressing degenerative disc disease, stenosis, and/or degenerative spondylolisthesis. METHODS: Several of Desai et al. large Spine Patient Outcomes Research Trial studies showed the frequency for nerve root injury following an open diskectomy ranged from 0.13% to 0.25%, for open laminectomy/stenosis with/without fusion it was 0%, and for open laminectomy/stenosis/degenerative spondylolisthesis with/without fusion it was 2%. RESULTS: Alternatively, one study compared the incidence of root injuries utilizing MIS transforaminal lumbar interbody fusion (TLIF) versus posterior lumbar interbody fusion (PLIF) techniques; 7.8% of PLIF versus 2% of TLIF patients sustained root injuries. Furthermore, even higher frequencies of radiculitis and nerve root injuries occurred during anterior lumbar interbody fusions (ALIFs) versus extreme lateral interbody fusions (XLIFs). These high frequencies were far from acceptable; 15.8% following ALIF experienced postoperative radiculitis, while 23.8% undergoing XLIF sustained root/plexus deficits. CONCLUSIONS: This review indicates that MIS (TLIF/PLIF/ALIF/XLIF) lumbar surgery resulted in a higher incidence of root injuries, radiculitis, or plexopathy versus open lumbar surgical techniques. Furthermore, even a cursory look at the XLIF data demonstrated the greater danger posed to neural tissue by this newest addition to the MIS lumbar surgical armamentariu. The latter should prompt us as spine surgeons to question why the XLIF procedure is still being offered to our patients? PMID- 26904373 TI - More nerve root injuries occur with minimally invasive lumbar surgery: Let's tell someone. AB - BACKGROUND: In a recent study entitled: "More nerve root injuries occur with minimally invasive lumbar surgery, especially extreme lateral interbody fusion (XLIF): A review", Epstein documented that more nerve root injuries occurred utilizing minimally invasive surgery (MIS) versus open lumbar surgery for diskectomy, decompression of stenosis (laminectomy), and/or fusion for instability. METHODS: In large multicenter Spine Patient Outcomes Research Trial reviews performed by Desai et al., nerve root injury with open diskectomy occurred in 0.13-0.25% of cases, occurred in 0% of laminectomy/stenosis with/without fusion cases, and just 2% for open laminectomy/stenosis/degenerative spondylolisthesis with/without fusion. RESULTS: In another MIS series performed largely for disc disease (often contained nonsurgical disc herniations, therefore unnecessary procedures) or spondylolisthesis, the risk of root injury was 2% for transforaminal lumbar interbody fusion (TLIF) versus 7.8% for posterior lumbar interbody fusion (PLIF). Furthermore, the high frequencies of radiculitis/nerve root/plexus injuries incurring during anterior lumbar interbody fusions (ALIF: 15.8%) versus extreme lumbar interbody fusions (XLIF: 23.8%), addressing disc disease, failed back surgery, and spondylolisthesis, were far from acceptable. CONCLUSIONS: The incidence of nerve root injuries following any of the multiple MIS lumbar surgical techniques (TLIF/PLIF/ALIF/XLIF) resulted in more nerve root injuries when compared with open conventional lumbar surgical techniques. Considering the majority of these procedures are unnecessarily being performed for degenerative disc disease alone, spine surgeons should be increasingly asked why they are offering these operations to their patients? PMID- 26904374 TI - Predicting Clinical Binary Outcome Using Multivariate Longitudinal Data: Application to Patients with Newly Diagnosed Primary Open-Angle Glaucoma. AB - Primary open angle glaucoma (POAG) is a chronic, progressive, irreversible, and potentially blinding optic neuropathy. The risk of blindness due to progressive visual field (VF) loss varies substantially from patient to patient. Early identification of those patients destined to rapid progressive visual loss is crucial to prevent further damage. In this article, a latent class growth model (LCGM) was developed to predict the binary outcome of VF progression using longitudinal mean deviation (MD) and pattern standard deviation (PSD). Specifically, the trajectories of MD and PSD were summarized by a functional principal component (FPC) analysis, and the estimated FPC scores were used to identify subgroups (latent classes) of individuals with distinct patterns of MD and PSD trajectories. Probability of VF progression for an individual was then estimated as weighted average across latent classes, weighted by posterior probability of class membership given baseline covariates and longitudinal MD/PSD series. The model was applied to the participants with newly diagnosed POAG from the Ocular Hypertension Treatment Study (OHTS), and the OHTS data was best fit by a model with 4 latent classes. Using the resultant optimal LCGM, the OHTS participants with and without VF progression could be accurately differentiated by incorporating longitudinal MD and PSD. PMID- 26904376 TI - Composite non-LTR retrotransposons in hominoid primates. AB - Composite retrotransposons are widely distributed in the plant and animal kingdoms. Some of the most complex of these are found in hominoid primates. SVA, LAVA, PVA and FVA combine simple repeats, Alu fragments, a VNTR (Variable Number of Tandem Repeats) and variable 3' domains, which are, except for PVA, derived from other retrotransposons. Although a likely precursor of SVA-a "tailed VNTR" named SVA2-had been identified in the Rhesus genome, the exact sequence and mechanism of the assembly of this type of composite retrotransposon had been elusive. The discovery of LAVA, PVA and FVA in gibbons provided the opportunity to delineate the order of assembly of the components of VNTR-containing retrotransposons. Our recent analysis suggests that an extinct "Alu-SVA2" acquired variant 3' ends by splicing. In this commentary I will discuss the mode of assembly of VNTR composites in the context of their capacity to engage in alternative splicing to co-mobilize host RNA sequences and to become exonized. The second part will focus on structural determinants of VNTR composite retrotransposon mobilization in the context of lineage-specific expansion of particular families/subfamilies of these elements. PMID- 26904375 TI - Transposable elements and small RNAs: Genomic fuel for species diversity. AB - While transposable elements (TE) have long been suspected of involvement in species diversification, identifying specific roles has been difficult. We recently found evidence of TE-derived regulatory RNAs in a species-rich family of bats. The TE-derived small RNAs are temporally associated with the burst of species diversification, suggesting that they may have been involved in the processes that led to the diversification. In this commentary, we expand on the ideas that were briefly touched upon in that manuscript. Specifically, we suggest avenues of research that may help to identify the roles that TEs may play in perturbing regulatory pathways. Such research endeavors may serve to inform evolutionary biologists of the ways that TEs have influenced the genomic and taxonomic diversity around us. PMID- 26904378 TI - Protection of Erwinia amylovora bacteriophage Y2 from UV-induced damage by natural compounds. AB - Bacteriophages have regained much attention as biocontrol agents against bacterial pathogens. However, with respect to stability, phages are biomolecules and are therefore sensitive to a number of environmental influences. UV irradiation can readily inactivate phage infectivity, which impedes their potential application in the plant phyllosphere. Therefore, phages for control of Erwinia amylovora, the causative agent of fire blight, need to be protected from UV-damage by adequate measures. We investigated the protective effect of different light-absorbing substances on phage particles exposed to UV-light. For this, natural extracts from carrot, red pepper, and beetroot, casein and soy peptone in solution, and purified substances such as astaxanthin, aromatic amino acids, and Tween 80 were prepared and tested as natural sunscreens for phage. All compounds were found to significantly increase half-life of UV-irradiated phage particles and they did not negatively affect phage viability or infectivity. Altogether, a range of readily available, natural substances are suitable as UV protectants to prevent phage particles from UV-light damage. PMID- 26904377 TI - The peculiarities of piRNA expression upon heat shock exposure in Drosophila melanogaster. AB - Different types of stress including heat shock may induce genomic instability, due to the derepression and amplification of mobile elements (MEs). It remains unclear, however, whether piRNA-machinery regulating ME expression functions normally under stressful conditions. The aim of this study was to explore the features of piRNA expression after heat shock (HS) exposure in Drosophila melanogaster. We also evaluated functioning of piRNA-machinery in the absence of major stress protein Hsp70 in this species. We analyzed the deep sequence data of piRNA expression after HS treatment and demonstrated that it modulates the expression of certain double-stranded germinal piRNA-clusters. Notable, we demonstrated significant changes in piRNA levels targeting a group of MEs after HS only in the strain containing normal set of hsp70 genes. Surprisingly, we failed to detect any correlation between the levels of piRNAs and the transcription of complementary MEs in the studied strains. We propose that modulation of certain piRNA-clusters expression upon HS exposure in D. melanogaster occurs due to HS-induced altering of chromatin state at certain chromosome regions. PMID- 26904379 TI - Isolation and characterization of a novel phage lysin active against Paenibacillus larvae, a honeybee pathogen. AB - Paenibacillus larvae is the causative agent of American foulbrood (AFB) disease which affects early larval stages during honeybee development. Due to its virulence, transmissibility, capacity to develop antibiotic resistance, and the inherent resilience of its endospores, Paenibacillus larvae is extremely difficult to eradicate from infected hives which often must be burned. AFB contributes to the worldwide decline of honeybee populations, which are crucial for pollination and the food supply. We have isolated a novel bacteriophage lysin, PlyPalA, from the genome of a novel Paenibacillus larvae bacteriophage originally extracted from an environmental sample. PlyPalA has an N-terminal N acetylmuramoyl-L-alanine amidase catalytic domain and possesses lytic activity against infectious strains of Paenibacillus larvae without harming commensal bacteria known to compose the honeybee larval microbiota. A single dose of PlyPalA rescued 75% of larvae infected with endospores, showing that it represents a powerful tool for future treatment of AFB. This represents the first time that lysins have been tested for therapeutic use in invertebrates. PMID- 26904380 TI - Adding pieces to the puzzle: New insights into bacteriophage diversity from integrated research-education programs. AB - Bacteriophages are the dark matter of the biological universe: the population is vast and replete with novel genes whose function is unknown. The genomic insights such as the mosaic architecture gleaned from perhaps 2,000 currently sequenced bacteriophage genomes is far from representative of the total number phage particles in the biosphere - about 10^31. The recent comparative analysis of 627 mycobacteriophages isolated on Mycobacterium smegmatis mc2 155 is the most extensive examination yet in pursuit of this question. PMID- 26904382 TI - Lamotrigine as monotherapy in clinical practice: efficacy of various dosages in epilepsy. AB - OBJECTIVES/AIMS: The study was designed to evaluate the optimal dosage of lamotrigine, as monotherapy, in the treatment of adults suffering from complex partial seizures with or without secondary generalization in everyday clinical practice. MATERIALS AND METHODS: The ones used in this study was the collection of the data of all adult patients treated with lamotrigine, retrospectively. The dosage and efficacy of treatment were evaluated along with side effects and retention rate. RESULTS: They showed that, out of 188 patients, 77% continued lamotrigine treatment; the mean effective dose was 250 mg or higher of lamotrigine, and the results more pronounced in older patients (age above 30 years) and those with a longer disease duration (5 years and more). CONCLUSION: It may be appropriate to reach a daily lamotrigine dose above 250 mg in adult patients suffering from epilepsy for more than 5 years using lamotrigine as monotherapy. PMID- 26904381 TI - Pre-early functions of bacteriophage T5 and its relatives. AB - Coliphage T5 injects its DNA in 2 steps: the first step transfer (FST) region 7.9% is injected and its genes are expressed and only then does the remainder (second step transfer, SST) of its DNA enter the cell. In the FST region, only 2 essential genes (A1 and A2) have been identified and a third (dmp) non-essential gene codes for a deoxyribonucleotide 5' monophosphatase. Thirteen additional putative ORFs are present in the FST region. Numerous properties have been attributed to FST region, including SST, host DNA degradation, inhibition of host RNA and protein synthesis, restriction insensitivity and protection of T5 DNA. These effects do not occur following infection with an A1 mutant. The A2 gene seems only to be involved in SST transfer. This is puzzling since there are more seemingly unrelated effects than there are essential genes to accomplish them and it is possible that some important genes were not identified. This review attempts to analyze these problems that were first identified in the 1970-80 s. In particular, an attempt is made to determine which potential ORFs are conserved in evolution (and thus likely to be important); by comparing T5 to 10 newly isolated and completely sequenced T5-like phages. A similar approach is used to identify conserved repeats, inverted repeats and palindromes that occur in all T5 like phages in the region containing the injection stop signal (iss) and the terminase substrate. Finally, an attempt is made to re-analyze the mechanism whereby T5 protects itself from the enzymes that degrade host DNA, from the RecBCD nuclease and from restriction enzymes. For all of these FST effects new hypotheses and possible new genetic and biochemical approaches are envisaged. PMID- 26904383 TI - Population PK-PD Model for Tolerance Evaluation to the p38 MAP Kinase Inhibitor BCT197. AB - The p38 mitogen-activated protein kinase (p38) is a key signaling pathway involved in regulation of inflammatory cytokines. Unexpectedly, several clinical studies using p38 inhibitors found no convincing clinical efficacy in the treatment of chronic inflammation. It was the objective of this study to characterize the population pharmacokinetics (PK) of BCT197 in healthy volunteers and to examine the relationship between BCT197 exposure and pharmacodynamics (PD) measured as inhibition of ex vivo lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNFalpha), a downstream marker of p38 activity. PK was characterized using a two-compartment model with mixed-order absorption and limited-capacity tissue binding. The PK-PD relationship revealed that suppression of TNFalpha was partly offset over time, despite continuous drug exposure. This may indicate a mechanism by which the inflammatory response acquires the ability to bypass p38. Simulations of posology dependence in drug effect suggest that an intermittent regimen may offer clinical benefit over continuous dosing and limit the impact of tolerance development. PMID- 26904384 TI - Quantitative prediction and clinical evaluation of an unexplored herb-drug interaction mechanism in healthy volunteers. AB - Quantitative prediction of herb-drug interaction risk remains challenging. A quantitative framework to assess a potential interaction was used to evaluate a mechanism not previously tested in humans. The semipurified milk thistle product, silibinin, was selected as an exemplar herbal product inhibitor of raloxifene intestinal glucuronidation. Physiologically based pharmacokinetic (PBPK) model simulations of the silibinin-raloxifene interaction predicted up to 30% increases in raloxifene area under the curve (AUC0-inf) and maximal concentration (Cmax). Model-informed clinical evaluation of the silibinin-raloxifene interaction indicated minimal clinical interaction liability, with observed geometric mean raloxifene AUC0-inf and Cmax ratios lying within the predefined no effect range (0.75-1.33). Further refinement of PBPK modeling and simulation approaches will enhance confidence in predictions and facilitate generalizability to additional herb-drug combinations. This quantitative framework can be used to develop guidances to evaluate potential herb-drug interactions prospectively, providing evidenced-based information about the risk or safety of these interactions. PMID- 26904385 TI - A Tumor Growth Inhibition Model Based on M-Protein Levels in Subjects With Relapsed/Refractory Multiple Myeloma Following Single-Agent Carfilzomib Use. AB - Change in tumor size estimated using longitudinal tumor growth inhibition (TGI) modeling is an early predictive biomarker of clinical outcomes for multiple cancer types. We present the application of TGI modeling for subjects with multiple myeloma (MM). Longitudinal time course changes in M-protein data from relapsed and/or refractory MM subjects who received single-agent carfilzomib in phase II studies (n = 456) were fit to a TGI model. The tumor growth rate estimate was similar to that of other anti-myeloma agents, indicating that the model is robust and treatment-independent. An overall survival model was subsequently developed, which showed that early change in tumor size (ECTS) at week 4, Eastern Cooperative Oncology Group performance status (ECOG PS), hemoglobin, sex, percent bone marrow cell involvement, and number of prior regimens were significant independent predictors for overall survival (P < 0.001). ECTS based on M-protein modeling could be an early biomarker for survival in MM following exposure to single-agent carfilzomib. PMID- 26904386 TI - Modeling and predicting optimal treatment scheduling between the antiangiogenic drug sunitinib and irinotecan in preclinical settings. AB - We present a system of nonlinear ordinary differential equations used to quantify the complex dynamics of the interactions between tumor growth, vasculature generation, and antiangiogenic treatment. The primary dataset consists of longitudinal tumor size measurements (1,371 total observations) in 105 colorectal tumor-bearing mice. Mice received single or combination administration of sunitinib, an antiangiogenic agent, and/or irinotecan, a cytotoxic agent. Depending on the dataset, parameter estimation was performed either using a mixed effect approach or by nonlinear least squares. Through a log-likelihood ratio test, we conclude that there is a potential synergistic interaction between sunitinib when administered in combination with irinotecan in preclinical settings. Model simulations were then compared to data from a follow-up preclinical experiment. We conclude that the model has predictive value in identifying the therapeutic window in which the timing between the administrations of these two drugs is most effective. PMID- 26904387 TI - Prediction of Response to Temozolomide in Low-Grade Glioma Patients Based on Tumor Size Dynamics and Genetic Characteristics. AB - Both molecular profiling of tumors and longitudinal tumor size data modeling are relevant strategies to predict cancer patients' response to treatment. Herein we propose a model of tumor growth inhibition integrating a tumor's genetic characteristics (p53 mutation and 1p/19q codeletion) that successfully describes the time course of tumor size in patients with low-grade gliomas treated with first-line temozolomide chemotherapy. The model captures potential tumor progression under chemotherapy by accounting for the emergence of tissue resistance to treatment following prolonged exposure to temozolomide. Using information on individual tumors' genetic characteristics, in addition to early tumor size measurements, the model was able to predict the duration and magnitude of response, especially in those patients in whom repeated assessment of tumor response was obtained during the first 3 months of treatment. Combining longitudinal tumor size quantitative modeling with a tumor''s genetic characterization appears as a promising strategy to personalize treatments in patients with low-grade gliomas. PMID- 26904388 TI - Negative Affect Instability among Individuals with Comorbid Borderline Personality Disorder and Posttraumatic Stress Disorder. AB - Ecological momentary assessment (EMA; Stone & Shiffman, 1994) was utilized to examine affective instability (AI) in the daily lives of outpatients with borderline personality disorder (BPD; n=78) with and without posttraumatic stress disorder (PTSD). A psychiatric control group (n=50) composed of outpatients with major depressive disorder/dysthymia (MDD/DYS) was employed to compare across subgroups: BPD-only, BPD+PTSD, MDD/DYS-only, and MDD/DYS+PTSD. Compared to the BPD-only group, the BPD+PTSD group had significantly greater instability of fear and sadness, but did not significantly differ in instability of hostility or aggregate negative affect. This pattern of elevated instability of fear and sadness was not present-and, in fact, was reversed-in the MDD/DYS group. Results emphasize the importance of examining AI within the context of specific comorbidities and affect types. Treatment and research addressing AI in the context of BPD-PTSD comorbidity may benefit from a focus on fear and sadness as separate from hostility or general negative affect. PMID- 26904389 TI - Cocoa pod husk, a new source of hydrolase enzymes for preparation of cross-linked enzyme aggregate. AB - Cocoa pod husk (CPH) is a by-product of cocoa production obtained after removing the beans from the fruit. The analysis of CPH has shown that it contains high amounts of protein. This study is aimed to utilize this protein source in hydrolase enzyme production. In this study, seven hydrolase enzymes (amylase, fructosyltransferase, mannanase, glucosidase, glucanase, lipase and protease) were screened from CPH for the first time for feasible industrial production. Among these hydrolases, lipase was chosen for the next steps of experiments as it has a lot of applications in different industries. The extraction of high active lipase from CPH has been done under optimum conditions. The condition that was optimum for the three major factors was achieved using Face centered central composite design (FCCCD) with response surface methodology (RSM) to obtain the highest enzyme activity of crude lipase from CPH. The optimum condition of extraction is used for preparation of cross-linked enzyme aggregate (CLEA). For the production of immobilized biocatalyst, the technique of CLEA is considered as an effective technique for its industrially attractive advantages. Referring to the results of OFAT, CLEA-lipase was prepared in the best condition at the presence of 30 mM ammonium sulphate, 70 mM glutaraldehyde with 0.23 mM Bovine serum albumin as an additive. Immobilization effectively improved the stability of lipase against various organic solvents. PMID- 26904390 TI - Some equalities and inequalities for fusion frames. AB - Fusion frames have some properties similar to those of frames in Hilbert spaces, but not all of their properties are similar. Some authors have established some equalities and inequalities for conventional frames. In this paper, we give some equalities and inequalities for fusion frames. Our results generalize and improve the remarkable results which have been obtained by Balan, Casazza and Gavruta etc. PMID- 26904391 TI - Adaptive tight frame based multiplicative noise removal. AB - Sparse approximation has shown to be a significant tool in improving image restoration quality, assuming that the targeted images can be approximately sparse under some transform operators. However, it is impossible for a fixed system to be always optimal for all the images. In this paper, we present an adaptive wavelet tight frame technology for sparse representation of an image with multiplicative noise. The adaptive wavelet tight frame is first learned from the logarithmic transformed given images, and then it is used to recover these images. Compared with the existing non-adaptive wavelet sparse transform methods, the numerical results demonstrate that the proposed adaptive tight frame scheme improves image restoration quality. PMID- 26904392 TI - Healing period after open high tibial osteotomy and related factors: Can we really say that it is long? AB - High tibial osteotomy (HTO) is a general procedure for the treatment of degenerative gonarthrosis. In recent years, it has been reported that opening wedge high tibial osteotomy (OWHTO) has become widespread with good results. Despite these facts, HTOs tend to be avoided due to the need for long-term postoperative treatment. To investigate the treatment period for total recovery (healing period) after OWHTO and the factors affecting it. There were 47 cases of medial type degenerative gonarthrosis who underwent OWHTO from 2008 through 2011. The definition of the healing period was based on the time-dependent changes of the Japanese Orthopaedic Association score, focusing especially on pain on walking and pain on ascending/descending stairs. This score was defined as the Ability score. In this study, the healing period ended when the Ability score reached its maximum or when it showed a perfect score. Patients' characteristics were examined to determine their effect on the healing period. The Ability score was 36.7 +/- 10.1 (mean +/- SD) before surgery and 51.6 +/- 5.4 12 months after OWHTO. The healing period was 6.3 +/- 3.9 months. Factors correlated with a longer healing period included female sex (correlation coefficient -0.35) and high BMI (correlation coefficient 0.33). Our study suggested that the healing period after OWHTO is approximately 6 months, and patients' BMI and sex appear to be related to this period. This information is expected to be helpful for counseling patients undergoing treatment for gonarthrosis. Level of evidence Therapeutic study, Level IV. PMID- 26904393 TI - Plastic neo-vaginal construction in Mayer-Rokitansky-Kuster-Hauser syndrome: an expert opinion paper on the decision-making treatment process. AB - Vaginal agenesis is a congenital anomaly that affects the life of one of each four thousand women around the world. There is a trend that patients request immediate surgical correction, instead of passive vaginal dilatation. Therefore a differentiated counselling should be provided. We present a comparative chart, based on published evidence, with aspect to the available techniques, which will facilitate the decision-making process in the clinical practice. From our point of view, the best results are achieved with techniques that combine the advantages of the minimal-invasive surgery with those derived of the use of peritoneum as covering tissue of the neovagina. Nevertheless there is a lack on interdisciplinary consensus about the best option to restore the physical and sexual quality of life. PMID- 26904396 TI - Direct anti-HCV agents. AB - Unlike human immunodeficiency virus (HIV) and hepatitis B virus (HBV), hepatitis C virus (HCV) infection is a curable disease. Current direct antiviral agent (DAA) targets are focused on HCV NS3/4A protein (protease), NS5B protein (polymerase) and NS5A protein. The first generation of DAAs includes boceprevir and telaprevir, which are protease inhibitors and were approved for clinical use in 2011. The cure rate for genotype 1 patients increased from 45% to 70% when boceprevir or telaprevir was added to standard PEG-IFN/ribavirin. More effective and less toxic second generation DAAs supplanted these drugs by 2013. The second generation of DAAs includes sofosbuvir (Sovaldi), simeprevir (Olysio), and fixed combination medicines Harvoni and Viekira Pak. These drugs increase cure rates to over 90% without the need for interferon and effectively treat all HCV genotypes. With these drugs the "cure HCV" goal has become a reality. Concerns remain about drug resistance mutations and the high cost of these drugs. The investigation of new HCV drugs is progressing rapidly; fixed dose combination medicines in phase III clinical trials include Viekirax, asunaprevir+daclatasvir+beclabuvir, grazoprevir+elbasvir and others. PMID- 26904395 TI - 5'-Monophosphate-activated protein kinase (AMPK) improves autophagic activity in diabetes and diabetic complications. AB - Diabetes mellitus (DM), an endocrine disorder, will be one of the leading causes of death world-wide in about two decades. Cellular injuries and disorders of energy metabolism are two key factors in the pathogenesis of diabetes, which also become the important causes for the process of diabetic complications. AMPK is a key enzyme in maintaining metabolic homeostasis and has been implicated in the activation of autophagy in distinct tissues. An increasing number of researchers have confirmed that autophagy is a potential factor to affect or induce diabetes and its complications nowadays, which could remove cytotoxic proteins and dysfunctional organelles. This review will summarize the regulation of autophagy and AMPK in diabetes and its complications, and explore how AMPK stimulates autophagy in different diabetic syndromes. A deeper understanding of the regulation and activity of AMPK in autophagy would enhance its development as a promising therapeutic target for diabetes treatment. PMID- 26904397 TI - Structural optimization and biological evaluation of 1,5-disubstituted pyrazole-3 carboxamines as potent inhibitors of human 5-lipoxygenase. AB - Human 5-lipoxygenase (5-LOX) is a well-validated drug target and its inhibitors are potential drugs for treating leukotriene-related disorders. Our previous work on structural optimization of the hit compound 2 from our in-house collection identified two lead compounds, 3a and 3b, exhibiting a potent inhibitory profile against 5-LOX with IC50 values less than 1 umol/L in cell-based assays. Here, we further optimized these compounds to prepare a class of novel pyrazole derivatives by opening the fused-ring system. Several new compounds exhibited more potent inhibitory activity than the lead compounds against 5-LOX. In particular, compound 4e not only suppressed lipopolysaccharide-induced inflammation in brain inflammatory cells and protected neurons from oxidative toxicity, but also significantly decreased infarct damage in a mouse model of cerebral ischemia. Molecular docking analysis further confirmed the consistency of our theoretical results and experimental data. In conclusion, the excellent in vitro and in vivo inhibitory activities of these compounds against 5-LOX suggested that these novel chemical structures have a promising therapeutic potential to treat leukotriene-related disorders. PMID- 26904394 TI - Regulation of AMP-activated protein kinase by natural and synthetic activators. AB - The AMP-activated protein kinase (AMPK) is a sensor of cellular energy status that is almost universally expressed in eukaryotic cells. While it appears to have evolved in single-celled eukaryotes to regulate energy balance in a cell autonomous manner, during the evolution of multicellular animals its role has become adapted so that it also regulates energy balance at the whole body level, by responding to hormones that act primarily on the hypothalamus. AMPK monitors energy balance at the cellular level by sensing the ratios of AMP/ATP and ADP/ATP, and recent structural analyses of the AMPK heterotrimer that have provided insight into the complex mechanisms for these effects will be discussed. Given the central importance of energy balance in diseases that are major causes of morbidity or death in humans, such as type 2 diabetes, cancer and inflammatory disorders, there has been a major drive to develop pharmacological activators of AMPK. Many such activators have been described, and the various mechanisms by which these activate AMPK will be discussed. A particularly large class of AMPK activators are natural products of plants derived from traditional herbal medicines. While the mechanism by which most of these activate AMPK has not yet been addressed, I will argue that many of them may be defensive compounds produced by plants to deter infection by pathogens or grazing by insects or herbivores, and that many of them will turn out to be inhibitors of mitochondrial function. PMID- 26904398 TI - Sesquiterpene glycosides from the roots of Codonopsis pilosula. AB - Three new sesquiterpene glycosides, named codonopsesquilosides A-C (1-3), were isolated from an aqueous extract of the dried roots of Codonopsis pilosula. Their structures including absolute configurations were determined by spectroscopic and chemical methods. These glycosides are categorized as C15 carotenoid (1), gymnomitrane (2), and eudesmane (3) types of sesquiterpenoids, respectively. Compound 1 is the first diglycoside of C15 carotenoids to be reported. Compound 2 represents the second reported example of gymnomitrane-type sesquiterpenoids from higher plants. The absolute configurations were supported by comparison of the experimental circular dichroism (CD) spectra with the calculated electronic CD (ECD) spectra of 1-3, their aglycones, and model compounds based on quantum mechanical time-dependent density functional theory. The influences of the glycosyls on the calculated ECD spectra of the glycosidic sesquiterpenoids, as well as some nomenclature and descriptive problems with gymnomitrane-type sesquiterpenoids are discussed. PMID- 26904399 TI - Development and validation of an HPLC-MS/MS method to determine clopidogrel in human plasma. AB - A quantitative method for clopidogrel using online-SPE tandem LC-MS/MS was developed and fully validated according to the well-established FDA guidelines. The method achieves adequate sensitivity for pharmacokinetic studies, with lower limit of quantifications (LLOQs) as low as 10 pg/mL. Chromatographic separations were performed on reversed phase columns Kromasil Eternity-2.5-C18-UHPLC for both methods. Positive electrospray ionization in multiple reaction monitoring (MRM) mode was employed for signal detection and a deuterated analogue (clopidogrel-d 4) was used as internal standard (IS). Adjustments in sample preparation, including introduction of an online-SPE system proved to be the most effective method to solve the analyte back-conversion in clinical samples. Pooled clinical samples (two levels) were prepared and successfully used as real-sample quality control (QC) in the validation of back-conversion testing under different conditions. The result showed that the real samples were stable in room temperature for 24 h. Linearity, precision, extraction recovery, matrix effect on spiked QC samples and stability tests on both spiked QCs and real sample QCs stored in different conditions met the acceptance criteria. This online-SPE method was successfully applied to a bioequivalence study of 75 mg single dose clopidogrel tablets in 48 healthy male subjects. PMID- 26904400 TI - Pharmacokinetic study of gallocatechin-7-gallate from Pithecellobium clypearia Benth. in rats. AB - The pharmacokinetic profile of gallocatechin-7-gallate (J10688) was studied in rats after intravenous administration. Male and female Sprague-Dawley (SD) rats received 1, 3, and 10 mg/kg (i.v.) of J10688 and plasma drug concentrations were determined by a high performance liquid chromatography-mass spectrometry (LC-MS) method. The pharmacokinetic software Data Analysis System (Version 3.0) was used to calculate the pharmacokinetic parameters. For different i.v. doses of J10688, the mean peak plasma concentration (C 0) values ranged from 11.26 to 50.82 mg/L, and mean area under the concentration-time curve (AUC0-t ) values ranged from 1.75 to 11.80 (mg.h/L). J10688 lacked dose-dependent pharmacokinetic properties within doses between 1 and 10 mg/kg, based on the power model. The method developed in this study was sensitive, precise, and stable. The pharmacokinetic properties of J10688 in SD rats were shown to have rapid distribution and clearance values. These pharmacokinetic results may contribute to an improved understanding of the pharmacological actions of J10688. PMID- 26904401 TI - Implementation of a reference-scaled average bioequivalence approach for highly variable generic drug products of agomelatine in Chinese subjects. AB - The aim of this study was to apply the reference-scaled average bioequivalence (RSABE) approach to evaluate the bioequivalence of 2 formulations of agomelatine, and to investigate the pharmacokinetic properties of agomelatine in Chinese healthy male subjects. This was performed in a single-dose, randomized-sequence, open-label, four-way crossover study with a one-day washout period between doses. Healthy Chinese males were randomly assigned to receive 25 mg of either the test or reference formulation. The formulations were considered bioequivalent if 90% confidence intervals (CIs) for the log-transformed ratios and ratio of geometric means (GMR) of AUC and C max of agomelatine were within the predetermined bioequivalence range based on RSABE method. Results showed that both of the 90% CIs for the log-transformed ratios of AUC and C max of 7-desmethyl-agomelatine and 3-hydroxy-agomelatine were within the predetermined bioequivalence range. The 90% CIs for natural log-transformed ratios of C max, AUC0-t and AUC0-infinity of agomelatine (104.42-139.86, 101.33-123.83 and 97.90-117.94) were within the RSABE acceptance limits, and 3-hydroxy-agomelatine (105.55-123.03, 101.95-109.10 and 101.72-108.70) and 7-desmethyl-agomelatine (104.50-125.23, 102.36-111.50 and 101.62-110.64) were within the FDA bioequivalence definition intervals (0.80-1.25 for AUC and 0.75-1.33 for C max). The RSABE approach was successful in evaluating the bioequivalence of these two formulations. PMID- 26904402 TI - Factors to consider in developing individual pharmaceutical product quality risk profiles useful to government procurement agencies. AB - Governments that procure pharmaceutical products from an Essential Medicine List (EML) bear special responsibility for the quality of these products. In this article we examine the possibility of developing a pharmaceutical product quality risk assessment scheme for use by government procurement officials. We use the Chinese EML as a basis, and US recall data is examined as it is publically available.This is justified as the article is only concerned with inherent product quality risks. After establishing a link between Chinese essential medicines and those available in the US, we examine US recall data to separate product specific recalls. We conclude that, in addition to existing manufacturing based risks, there are two other product specific risks that stand out from all others, degradation and dissolution failure. Methodology for relative product risk for degradation is needed to be developed and further work is required to better understand dissolution failures which largely occur with modified-release solid oral products. We conclude that a product specific quality risk profile would be enhanced by including a risk assessment for degradation for all products, and in the case of solid oral products, dissolution. PMID- 26904403 TI - Tetrahydroisoquinolines as novel histone deacetylase inhibitors for treatment of cancer. AB - Histone acetylation is a critical process in the regulation of chromatin structure and gene expression. Histone deacetylases (HDACs) remove the acetyl group, leading to chromatin condensation and transcriptional repression. HDAC inhibitors are considered a new class of anticancer agents and have been shown to alter gene transcription and exert antitumor effects. This paper describes our work on the structural determination and structure-activity relationship (SAR) optimization of tetrahydroisoquinoline compounds as HDAC inhibitors. These compounds were tested for their ability to inhibit HDAC 1, 3, 6 and for their ability to inhibit the proliferation of a panel of cancer cell lines. Among these, compound 82 showed the greatest inhibitory activity toward HDAC 1, 3, 6 and strongly inhibited growth of the cancer cell lines, with results clearly superior to those of the reference compound, vorinostat (SAHA). Compound 82 increased the acetylation of histones H3, H4 and tubulin in a concentration dependent manner, suggesting that it is a broad inhibitor of HDACs. PMID- 26904404 TI - Clonal evolution of AML on novel FMS-like tyrosine kinase-3 (FLT3) inhibitor therapy with evolving actionable targets. AB - For acute myeloid leukemia (AML), identification of activating mutations in the FMS-like tyrosine kinase-3 (FLT3) has led to the development of several FLT3 inhibitors. Here we present clinical and next generation sequencing data at the time of progression of a patient on a novel FLT3-inhibitor clinical trial (ASP2215) to show that employing therapeutic interventions with these novel targeted therapies can lead to consequences secondary to selective pressure and clonal evolution of cancer. We describe novel findings alongside data on treatment directed towards actionable aberrations acquired during the process. ( CLINICAL TRIAL: NCT02014558; registered at: ). PMID- 26904406 TI - TAU focused issue on adult management of neurogenic bladder. PMID- 26904407 TI - Long-term complications following bladder augmentations in patients with spina bifida: bladder calculi, perforation of the augmented bladder and upper tract deterioration. AB - BACKGROUND: We desire to review our experience with bladder augmentation in spina bifida patients followed in a transitional and adult urologic practice. This paper will specifically focus on three major complications: bladder calculi, the most frequent complication found following bladder augmentation, perforation of the augmentation, its most lethal complication and finally we will address loss of renal function as a direct result of our surgical reconstructive procedures. METHODS: We reviewed a prospective data base maintained on patients with spina bifida followed in our transitional and adult urology clinic from 1986 to date. Specific attention was given to patients who had developed bladder calculi, sustained a spontaneous perforation of the augmented bladder or had developed new onset of renal scarring or renal insufficiency (>= stage 3 renal failure) during prolonged follow-up. RESULTS: The development of renal stones (P<0.05) and symptomatic urinary tract infections (P<0.0001) were found to be significantly reduced by the use of high volume (>=240 mL) daily bladder wash outs. Individuals who still developed bladder calculi recalcitrant to high volume wash outs were not benefited by the correction of underlying metabolic abnormalities or mucolytic agents. Spontaneous bladder perforations in the adult patient population with spina bifida were found to be directly correlated to substance abuse and noncompliance with intermittent catheterization, P<0.005. Deterioration of the upper tracts as defined by the new onset of renal scars occurred in 40% (32/80) of the patients managed by a ileocystoplasty and simultaneous bladder neck outlet procedure during a median follow-up interval 14 years (range, 8-45 years). Development of >= stage 3 chronic renal failure occurred within 38% (12/32) of the patients with scarring i.e., 15% (12/80) of the total patient population. Prior to the development of the renal scarring, 69% (22/32) of the patients had been noncompliant with intermittent catheterization. The onset of upper tract deterioration (i.e., new scar formation, hydronephrosis, calculus development, decrease in renal function) was silent, that is, clinically asymptomatic in one third (10/32 pts). CONCLUSIONS: This paper documents the need for high volume bladder irrigations to both prevent the most common complication following bladder augmentation, which is the development of bladder calculi and to reduce the incidence of symptomatic urinary tract infections. It provides a unique perspective regarding the impact of substance abuse and patient non compliance with medical directives as being both the most common cause for both spontaneous bladder rupture following augmentation cystoplasty and for deterioration of the upper tracts. These findings should cause the surgeon to reflect on his/her assessment of a patient prior to performing a bladder augmentation procedure and stress the need for close follow-up. PMID- 26904405 TI - Transdiagnostic commonalities and differences in resting state functional connectivity of the default mode network in schizophrenia and major depression. AB - Schizophrenia and depression are prevalent psychiatric disorders, but their underlying neural bases remains poorly understood. Neuroimaging evidence has pointed towards the relevance of functional connectivity aberrations in default mode network (DMN) hubs, dorso-medial prefrontal cortex and precuneus, in both disorders, but commonalities and differences in resting state functional connectivity of those two regions across disorders has not been formally assessed. Here, we took a transdiagnostic approach to investigate resting state functional connectivity of those two regions in 75 patients with schizophrenia and 82 controls from 4 scanning sites and 102 patients with depression and 106 controls from 3 sites. Our results demonstrate common dysconnectivity patterns as indexed by a significant reduction of functional connectivity between precuneus and bilateral superior parietal lobe in schizophrenia and depression. Furthermore, our findings highlight diagnosis-specific connectivity reductions of the parietal operculum in schizophrenia relative to depression. In light of evidence that points towards the importance of the DMN for social cognitive abilities and well documented impairments of social interaction in both patient groups, it is conceivable that the observed transdiagnostic connectivity alterations may contribute to interpersonal difficulties, but this could not be assessed directly in our study as measures of social behavior were not available. Given the operculum's role in somatosensory integration, diagnosis-specific connectivity reductions may indicate a pathophysiological mechanism for basic self-disturbances that is characteristic of schizophrenia, but not depression. PMID- 26904409 TI - Patient reported outcome measures in neurogenic bladder. AB - Many interventions for neurogenic bladder patients are directed towards improving quality of life (QOL). Patient reported outcome measures (PROMs) are the primary method of evaluating QOL, and they provide an important quantification of symptoms which can't be measured objectively. Our goal was to review general measurement principles, and identify and discuss PROMs relevant to neurogenic bladder patients. We identify two recent reviews of the state of the literature and updated the results with an additional Medline search up to September 1, 2015. Using the previous identified reviews, and our updated literature review, we identified 16 PROMs which are used for the assessment of QOL and symptoms in neurogenic bladder patients. Several are specifically designed for neurogenic bladder patients, such as the Qualiveen (for neurogenic bladder related QOL), and the Neurogenic Bladder Symptom Score (NBSS) (for neurogenic bladder symptoms). We also highlight general QOL measures for patients with multiple sclerosis (MS) and spinal cord injury (SCI) which include questions about bladder symptoms, and incontinence PROMs which are commonly used, but not specifically designed for neurogenic bladder patients. It is essential for clinicians and researchers with an interest in neurogenic bladder to be aware of the current PROMs, and to have a basic understanding of the principals of measurement in order to select the most appropriate one for their purpose. PMID- 26904408 TI - Not all neurogenic bladders are the same: a proposal for a new neurogenic bladder classification system. AB - Neurogenic bladder (NGB) has long been defined as a clinical entity that describes a heterogeneous collection of syndromes. The common theme is a bladder disorder concomitant with a neurologic disorder. This definition does not give the clinician much information about the bladder disorder, nor how to treat it, or even what the natural history of the disorder is likely to be. It may be time for a new classification scheme to better define the bladder defect and prognosis, as well as inform treatment. We propose a classification system based on seven categories, each having a neurologic defect in a distinct anatomic location. This is termed SALE (Stratify by Anatomic Location and Etiology). In addition, the presence or absence of bowel dysfunction and autonomic dysreflexia will be reported. In the future, as more definite prognostic information can be gleaned from biomarkers, we anticipate adding urinary nerve growth factor (NGF) and urinary brain-derived neurotrophic factor (BDNF) levels to the definition. We expect the SALE system to efficiently describe a patient suffering from NGB and simultaneously inform the most appropriate treatment, follow-up regimen, and long term prognosis. PMID- 26904410 TI - Urodynamic and physiologic patterns associated with the common causes of neurogenic bladder in adults. AB - The clinical presentation of the neurogenic bladder can be as vast as the pathologic causes however urodynamics (UDS) can help guide clinical decision making and help simplify a complex disease state. UDS may be considered as the gold standard in helping to break down complex and multifactorial voiding dysfunction into manageable goals; these include protecting the upper tracts, limiting urinary tract infections (UTI) via avoiding urinary stasis, and maintaining quality of life. Included within are examples of normal to pathologic tracings including normal filling and voiding, detrusor sphincteric coordination, changes in compliance, etc. Additionally we have provided expected UDS findings based on neurogenic disease process, including but not limited to, Parkinson's, dementia, multiple sclerosis (MS) and spinal cord injury based on lesion location. Pattern recognition and understanding of UDS can help lead to quality of life improvements and optimal management for the patient with neurogenic bladder dysfunction. PMID- 26904411 TI - Congenital causes of neurogenic bladder and the transition to adult care. AB - The population of patients with congenital genitourinary disorders has unique healthcare demands that require an additional interpersonal and medical skillset. Adults with congenital neurogenic bladder may have complex urinary anatomy, abnormal bladder function and atypical voiding mechanisms. While initial surgery and care of these patients is typically managed by a pediatric urologist, growth and development into adulthood necessitates transition of care to an adult care team. Failure of transition to adult care has been demonstrated to result in lower quality healthcare and increased risk of developing preventable complications. PMID- 26904412 TI - Medical management of neurogenic bladder with oral therapy. AB - This is a review of the most current literature on medical management of the neurogenic bladder (NGB) to treat detrusor overactivity (DO), improve bladder compliance and treat urinary incontinence. The use of antimuscarinics, alpha blockers, tricyclic antidepressants, desmopressin and mirabegron will be discussed along with combination therapy to improve efficacy. These medical therapies will be the focus of this review with surgical therapy and botulinum toxin injections being the subject of other articles in this series. PMID- 26904413 TI - The role of botulinum toxin A in treating neurogenic bladder. AB - Neurogenic detrusor overactivity (NDO) can result in lower and upper urinary tract complications and eventually even in end-stage kidney failure. Since the driving force of this clinical cascade is high bladder pressure, controlling intravesical pressure in NDO patients improves both quality of life and life expectancy in these patients. Botulinum toxin A (BTX-A) has proven its efficacy in reducing intravesical pressure and in reducing incontinence episodes. BTX-A also improves quality of life in patients with NDO. Both onabotulinumtoxinA (Botox((r)), Allergan, Irvine, USA) and abobotulinumtoxinA (Dysport((r)), Ipsen, Paris, France) have a level A recommendation for NDO-treatment. The recommended dose for intradetrusor injections in NDO patients is 200 U of onabotulinumtoxinA or 500 U of abobotulinumtoxinA. The drug is generally administered extratrigonal in the detrusor muscle, via cystoscopic guided injection at 20 sites in 1 mL injections. Intradetrusor BTX-A injections are safe, with mostly local complications such as urinary tract infection and high post-void residual or retention. The effect of the toxin lasts for approximately 9 months. Repeat injections can be performed without loss of efficacy. Different injection techniques, novel ways of BTX-A administration, eliminating the need for injection or new BTX-A types with better/longer response rates could change the field in the future. PMID- 26904414 TI - Urinary tract infection in the neurogenic bladder. AB - There is a high incidence of urinary tract infection (UTI) in patients with neurogenic lower urinary tract function. This results in significant morbidity and health care utilization. Multiple well-established risk factors unique to a neurogenic bladder (NB) exist while others require ongoing investigation. It is important for care providers to have a good understanding of the different structural, physiological, immunological and catheter-related risk factors so that they may be modified when possible. Diagnosis remains complicated. Appropriate specimen collection is of paramount importance and a UTI cannot be diagnosed based on urinalysis or clinical presentation alone. A culture result with a bacterial concentration of >=10(3) CFU/mL in combination with symptoms represents an acceptable definition for UTI diagnosis in NB patients. Cystoscopy, ultrasound and urodynamics should be utilized for the evaluation of recurrent infections in NB patients. An acute, symptomatic UTI should be treated with antibiotics for 5-14 days depending on the severity of the presentation. Antibiotic selection should be based on local and patient-based resistance patterns and the spectrum should be as narrow as possible if there are no concerns regarding urosepsis. Asymptomatic bacteriuria (AB) should not be treated because of rising resistance patterns and lack of clinical efficacy. The most important preventative measures include closed catheter drainage in patients with an indwelling catheter and the use of clean intermittent catheterization (CIC) over other methods of bladder management if possible. The use of hydrophilic or impregnated catheters is not recommended. Intravesical Botox, bacterial interference and sacral neuromodulation show significant promise for the prevention of UTIs in higher risk NB patients and future, multi-center, randomized controlled trials are required. PMID- 26904417 TI - Neuromodulation in neurogenic bladder. AB - While neuromodulation is a well-established treatment option for patients with non-neurogenic overactive bladder and urinary retention, its applicability to the neurogenic bladder population has only recently been examined more in depth. In this article we will discuss the outcomes, contraindications, and special considerations of sacral and percutaneous tibial nerve stimulation (PTNS) in patients with neurogenic lower urinary tract dysfunction. PMID- 26904415 TI - The treatment of erectile dysfunction in patients with neurogenic disease. AB - Erectile dysfunction (ED) related to compromise of the nervous system is an increasingly common occurrence. This may be due to the multifactorial nature of ED, the myriad of disorders affecting the neurotransmission of erectogenic signals, and improved awareness and diagnosis of ED. Nevertheless, neurogenic ED remains poorly understood and characterized. Disease related factors such as depression, decreased physical and mental function, the burden of chronic illness, and loss of independence may preclude sexual intimacy and lead to ED as well. The amount of data regarding treatment options in subpopulations of differing neurologic disorders remains scarce except for men with spinal cord injury. The treatment options including phosphodiesterase inhibitors, intracavernosal or intraurethral vasoactive agents, vacuum erection devices (VED) and penile prosthetic implantation remain constant. This review discusses the options in specific neurologic conditions, and briefly provides insight into new and future developments that may reshape the management of neurogenic ED. PMID- 26904416 TI - Fertility treatment in spinal cord injury and other neurologic disease. AB - Infertility in individuals with neurologic disorders is complex in etiology and manifestation. Its management therefore often requires a multimodal approach. This review addresses the implications of spinal cord injury (SCI) and other neurologic disease on fertility, including the high prevalence of sexual dysfunction, ejaculation disorders and compromised semen parameters. Available treatment approaches discussed include assisted ejaculation techniques and assisted reproductive technology including surgical sperm retrieval and intracytoplasmic sperm injection (ICSI). PMID- 26904418 TI - Detrusor sphincter dyssynergia: a review of physiology, diagnosis, and treatment strategies. AB - Detrusor sphincter dyssynergia (DSD) is the urodynamic description of bladder outlet obstruction from detrusor muscle contraction with concomitant involuntary urethral sphincter activation. DSD is associated with neurologic conditions such as spinal cord injury, multiple sclerosis, and spina bifida and some of these neurogenic bladder patients with DSD may be at risk for autonomic dysreflexia, recurrent urinary tract infections, or upper tract compromise if the condition is not followed and treated appropriately. It is diagnosed most commonly during the voiding phase of urodynamic studies using EMG recordings and voiding cystourethrograms, although urethral pressure monitoring could also potentially be used. DSD can be sub-classified as either continuous or intermittent, although adoption of this terminology is not widespread. There are few validated oral pharmacologic treatment options for this condition but transurethral botulinum toxin injection have shown temporary efficacy in reducing bladder outlet obstruction. Urinary sphincterotomy has also demonstrated reproducible long term benefits in several studies, but the morbidity associated with this procedure can be high. PMID- 26904419 TI - Reconstructive techniques for creation of catheterizable channels: tunneled and nipple valve channels. AB - Cutaneous catheterizable channels allow for continent bladder emptying when an alternate route is desired. The goals of channel creation in the neurogenic bladder population are successful urine elimination, renal preservation, continence and lastly cosmesis. In addition to a particular surgeon's comfort and experience with a given procedure, individual patient factors such as medical comorbidities, anatomic factors, and occupational function should be central to the selection of a surgical approach. An ideal channel is one that is short, straight, and well supported by associated blood supply and surrounding adventitia, so as to minimize difficulty with catheterization. Two types of channel continence mechanisms are discussed at length in this review-the tunneled channel, and the nipple valve. The appendicovesicostomy (Mitrofanoff), and reconfigured ileum (Yang-Monti) are both tunneled channels. The ileocecal valve is a commonly used nipple valve and provides continence when reinforced. The continent catheterizable ileal cecocystoplasty (CCIC) is an example of this channel technique. This method couples a tapered ileal limb as a catheterizable channel, the ileocecal valve as the continence mechanism, and the cecum and ascending colon as a bladder augmentation. While this procedure has higher perioperative complications relative to a simple tunneled channel, it has increased channel length flexibility and is also coupled with a bladder augment, which is completely performed using one bowel segment. Continent channel creation in adults can improve quality of life and minimize morbidity associated with neurogenic bladder. However, the decision to proceed with creation of a catheterizable channel should be made only after careful consideration of the patient's medical comorbidities, physical abilities social support, and surgeon experience. PMID- 26904421 TI - Professor Wayne J.G. Hellstrom: incidence of Peyronie's disease. PMID- 26904422 TI - Doctor Chris G. McMahon: epidemiology and diagnosis of ejaculatory dysfunction. PMID- 26904420 TI - Management options for sphincteric deficiency in adults with neurogenic bladder. AB - Neurogenic bladder is a very broad disease definition that encompasses varied disease and injury states affecting the bladder. The majority of patients with neurogenic bladder dysfunction do not have concomitant intrinsic sphincteric deficiency (ISD), but when this occurs the challenges of management of urinary incontinence from neurogenic bladder are compounded. There are no guidelines for surgical correction of ISD in adults and most of the literature on treatment of the problem comes from treatment of children with congenital diseases, such as myelomeningocele. Our goal, in this review, is to present some of the common surgical options for ISD [including artificial urinary sphincters, bladder slings, bladder neck reconstruction (BNR) and urethral bulking agents] and the evidence underlying these treatments in adults with neurogenic bladder. PMID- 26904423 TI - A step forward: Translational Andrology and Urology is indexed in PubMed/PMC. PMID- 26904424 TI - HMF-GUT2016 & GITAU2016 Invitation. PMID- 26904425 TI - Minimally invasive versus open thymectomy: a systematic review of surgical techniques, patient demographics, and perioperative outcomes. AB - BACKGROUND: Thymectomy is the mainstay of treatment for thymoma and other anterior mediastinal tumors, and is often utilized in the management of patients with myasthenia gravis (MG). While traditionally approached through a median sternotomy, minimally invasive approaches to thymectomy have increasingly emerged. The present systematic review was conducted to compare perioperative and clinical outcomes following minimally invasive thymectomy (MIT) and open thymectomy (OT). METHODS: Articles were obtained through a PubMed literature search. Comparative studies reporting clinical outcomes following MIT and OT were eligible for inclusion. We selected studies with full text availability, written in the English language, published after 2005 and with at least 15 patients in each arm. A descriptive analysis was performed. RESULTS: Twenty studies were included, involving a total of 2,068 patients undergoing either MIT (n=838) or OT (n=1,230). Within individual studies, MIT and OT cohorts were well matched with regards to patient age and gender, but there was considerable variation across studies. Resected thymomas were consistently larger in OT groups, with mean diameter significantly larger in five studies (MIT, 29-52 mm; OT, 31-77 mm). MIT was consistently associated with a lower estimated blood loss (MIT, 20-200 mL; OT, 86-466 mL), chest tube duration (MIT, 1.3-4.1 days; OT, 2.4-5.3 days), and hospital length of stay (MIT, 1-10.6 days; OT, 4-14.6 days). There were no consistent differences in rates of perioperative complications, thymoma recurrence, MG complete stable remission, or 5-year survival. CONCLUSIONS: In appropriately selected patients, MIT may reduce blood loss, chest tube duration, and hospital length of stay, with comparable clinical outcomes compared to OT via median sternotomy. PMID- 26904426 TI - Minimally invasive mediastinal surgery. AB - In the past, mediastinal surgery was associated with the necessity of a maximum exposure, which was accomplished through various approaches. In the early 1990s, many surgical fields, including thoracic surgery, observed the development of minimally invasive techniques. These included video-assisted thoracic surgery (VATS), which confers clear advantages over an open approach, such as less trauma, short hospital stay, increased cosmetic results and preservation of lung function. However, VATS is associated with several disadvantages. For this reason, it is not routinely performed for resection of mediastinal mass lesions, especially those located in the anterior mediastinum, a tiny and remote space that contains vital structures at risk of injury. Robotic systems can overcome the limits of VATS, offering three-dimensional (3D) vision and wristed instrumentations, and are being increasingly used. With regards to thymectomy for myasthenia gravis (MG), unilateral and bilateral VATS approaches have demonstrated good long-term neurologic results with low complication rates. Nevertheless, some authors still advocate the necessity of maximum exposure, especially when considering the distribution of normal and ectopic thymic tissue. In recent studies, the robotic approach has shown to provide similar neurological outcomes when compared to transsternal and VATS approaches, and is associated with a low morbidity. Importantly, through a unilateral robotic technique, it is possible to dissect and remove at least the same amount of mediastinal fat tissue. Preliminary results on early-stage thymomatous disease indicated that minimally invasive approaches are safe and feasible, with a low rate of pleural recurrence, underlining the necessity of a "no-touch" technique. However, especially for thymomatous disease characterized by an indolent nature, further studies with long follow-up period are necessary in order to assess oncologic and neurologic results through minimally invasive approaches. Furthermore, increased robotic experience and studies, including randomized controlled trials, are needed to validate the findings of the current literature. PMID- 26904427 TI - Multi-institutional European experience of robotic thymectomy for thymoma. AB - BACKGROUND: Robotic thymectomy for early-stage thymomas has been recently suggested as a technically sound and safe approach. However, due to a lack of data on long term results, controversy still exists regarding its oncological efficacy. In this multi-institutional series collected from four European Centres with high volumes of robotic procedures, we evaluate the results after robot assisted thoracoscopic thymectomy for thymoma. METHODS: Between 2002 and 2014, 134 patients (61 males and 73 females, median age 59 years) with a clinical diagnosis of thymoma were operated on using a left-sided (38%), right-sided (59.8%) or bilateral (2.2%) robotic approach. Seventy (52%) patients had associated myasthenia gravis (MG). RESULTS: The average operative time was 146 minutes (range, 60-353 minutes). Twelve (8.9%) patients needed open conversion: in one case, a standard thoracoscopy was performed after robotic system breakdown, and in six cases, an additional access was required. Neither vascular and nerve injuries, nor perioperative mortality occurred. A total of 23 (17.1%) patients experienced postoperative complications. Median hospital stay was 4 days (range, 2-35 days). Mean diameter of resected tumors was 4.4 cm (range, 1-10 cm), Masaoka stage was I in 46 (34.4%) patients, II in 71 (52.9%), III in 11 (8.3%) and IVa/b in 6 (4.4%) cases. At last follow up, 131 patients were alive, three died (all from non-thymoma related causes) with a 5-year survival rate of 97%. One (0.7%) patient experienced a pleural recurrence. CONCLUSIONS: Our data suggest that robotic thymectomy for thymoma is a technically feasible and safe procedure with low complication rates and short hospital stays. Oncological outcome appears to be good, particularly for early-stage tumors, but a longer follow-up period and more cases are necessary in order to consider this as a standard approach. Indications for robotic thymectomy for stage III or IVa thymomas are rare and should be carefully evaluated. PMID- 26904428 TI - Long term compensatory sweating results after sympathectomy for palmar and axillary hyperhidrosis. AB - BACKGROUND: Endoscopic thoracic sympathectomy is currently the best treatment for primary upper extremity hyperhidrosis, but the potential for adverse effects, particularly the development of compensatory sweating, is a concern and often precludes surgery as a definitive therapy. This study aims to evaluate long-term results of two-stage unilateral versus one-stage bilateral thoracoscopic sympathectomy. METHODS: From November 1995 to February 2011, 261 patients with severe palmar and/or axillary hyperhidrosis underwent endoscopic sympathectomy with a follow-up of at least 4 years. One-hundred and twenty-six patients received one-stage bilateral, single port video-assisted thoracoscopic sympathectomy (one-stage group) and 135 patients underwent two-stage unilateral, single-port video-assisted thoracoscopic sympathectomy, with a mean time interval of four months between the procedures (two-stage group). RESULTS: The mean postoperative follow-up period was 7.2 years (range, 4-9 years). Sixteen patients (12.7%) in the one-stage group and 15 patients (11.1%) in the two-stage group suffered from bradycardia (P=0.15). Recurrences occurred in three patients (2.4%) in the one-stage group and one (0.7%) in the two-stage group (P=0,09). Facial flushing or hyperthermia occurred in eight patients (6.3%) in the one-stage group and 11 (8.1%) of the two-stage group. Compensatory sweating occurred in 27 patients (21.4%) in the one-stage group and six patients (4.4%) in the two-stage group (P=0.0001). However, compensatory sweating recovered in five patients (83.3%) in the two-stage group versus nine (33.35%) in one-stage group during the follow-up period (Log-rank test P=0.016; HR, 7.196; 95% CI, 1.431-36.20). An improvement in postoperative quality of life (QoL) scores was observed in at least 90% of patients at three years after surgery in the one-stage group and at least 95% of patients in the two-stage group (P=0.001). CONCLUSIONS: Compensatory sweating seems to improve during the follow-up period with a higher recovery rate after two-stage unilateral versus one-stage bilateral sympathectomy for patients with palmar and axillary hyperhidrosis. PMID- 26904429 TI - Video-assisted thoracoscopic surgery versus sternotomy in thymectomy for thymoma and myasthenia gravis. AB - Thymectomy involves the removal of all the soft tissue in the pre-vascular plane of the anterior mediastinum between the two phrenic nerves. Surgical success in controlling myasthenia and the most important factor influencing survival in patients with thymoma depends on complete clearance of thymic tissue. Currently there is a perception that the open (median sternotomy) approach offers better visualisation of the thymic tissue. This perceived advantage is thought to justify the invasive nature of the procedure associated with increased morbidity. Video-assisted thoracoscopic surgery (VATS) for thymectomy has evolved significantly over the last decade, including bilateral and unilateral VATS (either left or right) approaches. The laterality of the approach remains largely on surgeon preferences, with the decision influenced by their experience and training. VATS offers superior illumination and magnification, particularly with the availability of advanced cameras with variable angles that provide better exposure and lighting of the operative field. The use of three-dimensional operating imaging has also revolutionised the VATS technique. VATS thymectomy is a superior and radical technique in minimising access trauma and removing all thymic tissue that may be scattered in the anterior mediastinum and cervical fat. Other advantages of VATS include less intraoperative blood loss, early removal of chest drains, less requirement for blood products, decreased inflammatory cytokine response, shorter hospital stay and superior cosmesis. There is also a decreased risk of respiratory and cardiac related complications compared to the open (sternotomy) technique. Furthermore, no significant difference has been found in long-term complications and survival rate between VATS and open approaches. Subsequently, the VATS approach should be encouraged as more surgeons are adopting the minimally invasive practice as routine. PMID- 26904430 TI - Endoscopic thymectomy: a neurologist's perspective. AB - Myasthenia gravis (MG) is an autoimmune neuromuscular disease characterized by the presence of antibodies interacting at the neuromuscular junction (NMJ), resulting in loss of strength and severe exhaustibility of striated muscles. The abnormal production of these antibodies is triggered mainly in the thymus, and hence thymectomy in MG is considered a universally recommended treatment in order to improve the symptomatologic condition of this pathology. Currently, minimally invasive thymectomy using the Da Vinci robot system is certainly one of the most innovative techniques, performed in Pisa since 2001. This approach provides a valuable alternative to the traditional thymectomy through median sternotomy. The contribution of a neurologist is fundamental for preoperative patient selection and for the peri-operative clinical assistance in both approaches. We believe that in the robotic approach, the multidisciplinary collaboration between the neurologist, thoracic surgeon and anesthetist is important in reducing perioperative complications and ensuring a higher rate of complete remission or stable clinical improvement of MG. PMID- 26904431 TI - The role of adjuvant chemotherapy following resection of early stage thymoma. AB - BACKGROUND: There is a paucity of data regarding adjuvant chemotherapy for resected early stage thymoma. This systematic review was designed to investigate the effect of adjuvant chemotherapy on outcomes in patients with early stage thymomas. METHODS: PubMed database was queried for studies containing information on adjuvant chemotherapy following surgery in patients with Masaoka stage I or II thymoma. RESULTS: Eight retrospective observational studies were reviewed. The number of patients with stage I or II thymoma was not clearly reported in several studies. Five studies reported on 890 patients with stage I or II patients, including 140 patients (15.7%) who received adjuvant chemotherapy with or without radiotherapy. No study reported short-term mortality in patients undergoing adjuvant chemotherapy following thymectomy. CONCLUSIONS: Adjuvant chemotherapy following resection of early thymomas appears to be a safe approach with favorable short-term outcomes. However, long-term outcomes remain unclear. There is no strong evidence to support adjuvant chemotherapy following resection of early-stage thymoma. PMID- 26904432 TI - Video-assisted thoracoscopic thymectomy using 5-mm ports and carbon dioxide insufflation. AB - The continuous development and refinement of minimally invasive approaches to thymectomy over the last two decades has potential benefits for patients in terms of better cosmesis, less postoperative pain, shorter length of stay, earlier return to daily activities, less bleeding and fewer complications overall with similar outcomes regarding survival, recurrence of thymoma and complete remission (CR) for myasthenia gravis patients. A variety of different approaches have been described previously. This is a detailed description of video-assisted thoracoscopic thymectomy using three 5 mm ports, carbon dioxide (CO2) insufflation and bipolar electrocoagulation (LigaSure). PMID- 26904433 TI - Single-port thymectomy using a subxiphoid approach-surgical technique. PMID- 26904434 TI - Minimally invasive radical thymectomy. PMID- 26904435 TI - Robotic surgery for posterior mediastinal pathology. PMID- 26904436 TI - Video-assisted thoracoscopic thymectomy using 5-mm ports and LigaSure. PMID- 26904437 TI - Video assisted transaxillary first rib resection in treatment of thoracic outlet syndrome (TOS). PMID- 26904438 TI - Mediastinal giant parathyroid adenoma-a minimally invasive mediastinal surgical approach for an emergency presentation. PMID- 26904439 TI - Myasthenia gravis. PMID- 26904440 TI - Malignant Mediterranean spotted fever. AB - Fever with rash is one of the most common causes of referral to a dermatologist. A plethora of conditions need to be considered in the differential diagnosis. They may be broadly classified into infectious causes, drug reactions, and autoimmune disorders. Here we present a rare case of rickettsial fever with cardiac involvement in an elderly male patient with no comorbidities. PMID- 26904441 TI - Rowell's syndrome in an Indian male and review of the literature. AB - Lupus erythematosus (LE) with erythema multiforme-like lesions with its characteristic serological picture had been described in 1963. We report a 33 year-old married male who presented with skin lesions of various morphology on different body parts since four months. The skin lesions ranged from lupus specific tumid LE to Rowell's syndrome and discoid LE. Histopathology of skin biopsy from all representative sites showed different forms of lupus erythematosus. Antinuclear and anti-double-stranded DNA was positive; however, serology for anti-SSA and anti-SSB was negative. There were no symptoms specific for organ involvement. It is unusual to document various morphological types in a single patient of lupus erythematosus. We document this case as all forms of cutaneous LE including Rowell's syndrome were evident in a single male patient. PMID- 26904442 TI - Annular elastolytic giant cell granuloma: A report of 10 cases. AB - Annular elastolytic giant cell granuloma initially described by O'Brien in 1975 is a disorder of uncertain etiopathogenesis presenting with annular erythematous plaques predominantly on the sun-exposed areas. Hisptopathologically, it is characterized by elastin degenration, multinucleate giant cells, and elastophagocytosis. The authors came across 10 such cases, which were managed with hydroxychloroquine resulting in complete resolution in 4-6 months. PMID- 26904443 TI - "Pink glow": A new sign for the diagnosis of glomus tumor on ultraviolet light dermoscopy. AB - Glomus tumors are usually benign hamartomas, which are painful, small, and uncommon. They are usually subungal in location but may occur at other sites. A female patient presented to the outpatient department with painful swelling over the nail matrix of her right index finger. Here, we describe the use of a videodermosope having white light, polarized light, and ultraviolet (UV) light in the localization of glomus tumors that revealed a pinkish glow on UV light examination suggesting the vascular nature of the tumor. Thus, videodermoscopy can be used as an outpatient department procedure to confirm the diagnosis of glomus tumors. PMID- 26904444 TI - Lymphomatoid contact dermatitis associated with textile dye at an unusual location. AB - Lymphomatoid contact dermatitis (LCD) is a rare variant of noneczematous allergic contact dermatitis, which can mimick parapsoriasis or early-stage mycosis fungoides with its atypical clinical and histopathological manifestation. Many different haptens have been reported to be associated with this reaction. Histopathological examination, immunhistochemistry, clonality tests, and patch tests are mandatory for diagnosis and differential diagnosis. We present a 48 year-old male with a four years history of a relapsing erythematous plaque on the glans penis. Topical corticosteroids had been prescribed but he complained of relapse upon withdrawal. Histopathological examination was consistent with LCD. Thin layer rapid use epicutaneous patch test result was (++) for disperse blue and nickel sulfate. We present this case because of its rarity and unusual localization. This kind of allergic contact dermatitis should be remembered in differential diagnosis of nonspesific pruritic plaques over the genital region. PMID- 26904445 TI - Sebaceous carcinoma on the abdomen in an African-American male patient. AB - Sebaceous carcinoma is a rare, aggressive cutaneous tumor most commonly involving the head and neck, especially the periorbital area. It has been associated with Muir-Torre syndrome, human papillomavirus infection, and radiotherapy. This case report describes an unusual clinical presentation of a large sebaceous carcinoma on the abdomen of an African-American male patient who was successfully treated with Mohs micrographic surgery. The case is reported due to the unusual location of the lesion on the abdomen and the rare occurrence of this tumor type in an African-American male. PMID- 26904446 TI - Zosteriform spiradenoma with spiradenocarcinoma: A rare entity. AB - Eccrine spiradenoma (ES) is an uncommon well-differentiated benign tumor originating from the sweat glands. It usually occurs as a single lesion in adults. Multiple ES in a linear or zosteriform distribution are rare. Spiradenomacarcinoma is an extremely rare tumor, which develops in an existing benign spiradenoma of several years of duration. We report a case of a 23-year old- female patient with multiple spiradenomas arranged in zosteriform pattern and malignant transformation occurred in one of the lesions over a period of 10 years. PMID- 26904447 TI - Histopathologic features in a case of hyperimmunoglobulinemia D syndrome. AB - We describe a case of Mevalonate Kinase Deficiency (MKD) also known as Hyperimmunoglobulinemia D Syndrome (HIDS) presenting as a Sweet-like syndrome in a 5-week-old with multiple erythematous plaques, fever, aseptic meningitis, and bronchiolitis. The locations of the predominant plaques were periumbilical and periocular, which originally prompted concern for omphalitis and preseptal cellulitis. Histopathology demonstrated a neutrophilic and histiocytic dermatitis with prominent squamous syringometaplasia and leukocytoclasis in the absence of a vasculitis. This case is reported here due to the unique findings of a prominent histiocytic component in addition to the typically described neutrophilic infiltrate. PMID- 26904448 TI - Calcinosis cutis secondary to facial acne vulgaris: A rare complication. AB - Acne vulgaris is a common dermatological disease commonly affecting the adolescent and young adults. It is characterized by the presence of pleomorphic skin lesions such as comadones, papules, pustules, and nodules. The common complications are postacne hyperpigmentation and scarring causing psychological impact. Calcinosis cutis is the pathologic deposition of insoluble calcium salt in the skin and subcutaneous tissue. Calcinosis cutis following acne vulgaris is rarely reported in the literature. We report a case of calcinosis cutis in acne vulgaris in a 55-year-old man. PMID- 26904449 TI - Spina ventosa with lupus vulgaris and lymphadenopathy: Multifocal tuberculosis. AB - Tuberculous dactylitis is a rare yet well-recognized disease of small bones of the hands and feet. It occurs in young children below five years of age. Tubercular dactylitis with lupus vulgaris and lymphadenopathy was suspected clinically and radiologically in an 8-year-old girl who had multiple soft tissue swelling of hands and feet with ulceration, encrustations, and an atrophic scar with lytic expansile lesions of the small bones of the hands and feet. Tubercular lymph node involvement was confirmed histopathologically. PMID- 26904450 TI - Tinea faciei caused by Trichophyton mentagrophytes in a 20-day-old neonate. AB - Although candidiasis in newborns is not uncommon, superficial dermatophyte infections of infants is quite rare. The causative agents of neonatal tinea reported in various case studies have been Trichophyton rubrum, Microsporum canis, Microsporum gypseum, and Trichophyton violaceum. To the best of our knowledge, no case report of neonatal tinea faciei caused by Trichophyton mentagrophytes has been reported earlier. PMID- 26904451 TI - Etoricoxib-induced pretibial erythema and edema. AB - Cyclooxygenase inhibitors were developed in the quest of enhanced analgesic efficacy devoid of gastric side effects. Etoricoxib is a second-generation cox-2 inhibitor and as its use increases so do the reports of side effects. We report a case of extoricoxib-induced pretibial erythema and edema; and review the literature. PMID- 26904452 TI - Squamous cell carcinoma developing in a long-standing case of tuberous xanthoma: An incident unreported hitherto. AB - Cutaneous squamous cell carcinoma, characterized by malignant transformation of normal epidermal keratinocyte is the second most common nonmelanoma skin cancer that has many predisposing factors. Tuberous xanthomas have not yet been reported as a predisposing factor. We report here the case of long-standing tuberous xanthoma in a middle-aged gentleman complicated by cutaneous squamous cell carcinoma, probably the first such report in the Indian literature. PMID- 26904453 TI - Dermpath quiz: An irregularly colored papule on the back of an adolescent female. AB - This learning exercise challenges clinicians and dermatopathologists to consider the differential diagnosis of an unevenly colored solitary papule over the upper back of an adolescent female. PMID- 26904454 TI - Dermatopathology quiz: A dome-shaped papule on the cheek. PMID- 26904455 TI - A case of verrucous hemangioma and its dermoscopic features. PMID- 26904456 TI - Diffuse scalp hair loss due to levothyroxine overdose. PMID- 26904457 TI - Dermatophyte infection encircling vitiligo. PMID- 26904458 TI - Giant pigmented Bowen's disease: A rare variant at a rare site. PMID- 26904459 TI - Asymptomatic esophageal varices in a case of pseudoxanthoma elasticum. PMID- 26904460 TI - Pyodermatitis vegetans after total colectomy. AB - Pyostomatitis-pyodermatitis vegetans (PPV) is a rare dermatological manifestation of inflammatory bowel disease, characterized by erythematous, vesiculopustular, exudative, annular, and/or vegetating plaques over the intertriginous regions that may precede or appear at the same time as the mucosal lesions. Systemic corticosteroids, dapsone, sulfasalazine, azathioprine, cyclosporine, and subtotal/total colectomy are the most common treatment options. A 16-year-old male patient presented to our outpatient clinic with a four months history of thickly crusted erosions on his trunk, back, and lower extremity. He had ulcerative colitis for four years and total colectomy was done seven months ago. Clinical and histopathological examination of his lesions were consistent with pyostomatitis vegetans. Although subtotal/total colectomy has been reported as a treatment option for PPV, lesions reappeared three months after total colectomy in our patient. PMID- 26904461 TI - Endocrinology, Evidence and Sherlock Holmes. PMID- 26904462 TI - Our journal: Arjuna's choice, Eklavya's voice. PMID- 26904463 TI - Biosimilar insulins: Informed choice for South Asia. PMID- 26904464 TI - Diabetes insipidus: The other diabetes. AB - Diabetes insipidus (DI) is a hereditary or acquired condition which disrupts normal life of persons with the condition; disruption is due to increased thirst and passing of large volumes of urine, even at night. A systematic search of literature for DI was carried out using the PubMed database for the purpose of this review. Central DI due to impaired secretion of arginine vasopressin (AVP) could result from traumatic brain injury, surgery, or tumors whereas nephrogenic DI due to failure of the kidney to respond to AVP is usually inherited. The earliest treatment was posterior pituitary extracts containing vasopressin and oxytocin. The synthetic analog of vasopressin, desmopressin has several benefits over vasopressin. Desmopressin was initially available as intranasal preparation, but now the oral tablet and melt formulations have gained significance, with benefits such as ease of administration and stability at room temperature. Other molecules used for treatment include chlorpropamide, carbamazepine, thiazide diuretics, indapamide, clofibrate, indomethacin, and amiloride. However, desmopressin remains the most widely used drug for the treatment of DI. This review covers the physiology of water balance, causes of DI and various treatment modalities available, with a special focus on desmopressin. PMID- 26904465 TI - Sodium-glucose cotransporter 2 inhibitors with insulin in type 2 diabetes: Clinical perspectives. AB - The treatment of type 2 diabetes is a challenging problem. Most subjects with type 2 diabetes have progression of beta cell failure necessitating the addition of multiple antidiabetic agents and eventually use of insulin. Intensification of insulin leads to weight gain and increased risk of hypoglycemia. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of antihyperglycemic agents which act by blocking the SGLT2 in the proximal tubule of the kidney. They have potential benefits in terms of weight loss and reduction of blood pressure in addition to improvements in glycemic control. Further, one of the SGLT2 inhibitors, empagliflozin has proven benefits in reducing adverse cardiovascular (CV) outcomes in a CV outcome trial. Adding SGLT2 inhibitors to insulin in subjects with type 2 diabetes produced favorable effects on glycemic control without the weight gain and hypoglycemic risks associated with insulin therapy. The general risks of increased genital mycotic infections, urinary tract infections, volume, and osmosis-related adverse effects in these subjects were similar to the pooled data of individual SGLT2 inhibitors. There are subsets of subjects with type 2 diabetes who may have insulin deficiency, beta cell autoimmunity, or is prone to diabetic ketoacidosis. In these subjects, SGLT2 inhibitors should be used with caution to prevent the rare risks of ketoacidosis. PMID- 26904466 TI - Dipeptidyl peptidase-4 inhibitors or sodium glucose co-transporter-2 inhibitors as an add-on to insulin therapy: A comparative review. AB - The gradual decline in beta-cell function is inevitable in type 2 diabetes mellitus and therefore, substantial proportions of patients require insulin subsequently, in order to achieve optimal glucose control. While weight gain, hypoglycemia, and fluid retention especially during dose intensification is a known limitation to insulin therapy, these adverse effects also reduce patient satisfaction and treatment adherence. It is also possible that the benefits of intensive control achieved by insulin therapy, perhaps get nullified by the weight gain and hypoglycemia. In addition, improvement in plasma glucose or glycated hemoglobin (HbA1c) itself is associated with weight gain. Notably, studies have already suggested that reduction in body weight by ~3-5%, may allow a significantly better glycemic control. Thus, a class of drugs, which can reduce HbA1c effectively, yet are weight neutral or preferably reduce body weight, could be the most sought out strategy as an add-on therapy to insulin. While sulfonylureas (SUs) are associated with weight gain and hypoglycemia, pioglitazone increases body weight and fluid retention. Moreover, SUs are not recommended once premix or prandial insulin is commenced. The addition of newer agents, such as glucagon-like peptide-1 receptor agonist to insulin certainly appears to be an effective tool in reducing both HbA1c and body weight as is evident across the studies; however, this approach incurs an additional injection as well as cost. Dipeptidyl peptidase-4 inhibitors (DPP-4I) and sodium-glucose co transporter-2 inhibitors (SGLT-2I) are other exciting options, as an add-on to insulin therapy primarily because these are oral drugs and do not possess any intrinsic potential of hypoglycemia. Furthermore, these are either weight neutral or induce significant weight loss. This review article aims to comparatively analyze the safety and efficacy of DPP-4I and SGLT-2I, as an add-on therapy to insulin. PMID- 26904467 TI - Need for testing glucose tolerance in the early weeks of pregnancy. AB - AIMS: This observational study aims to determine the frequency of occurrence of glucose intolerance in the early weeks of pregnancy. MATERIALS AND METHODS: New World Health Organization 2013 guidelines recommends "A Single Step Procedure" (SSP) as an option for diagnosing gestational diabetes mellitus (GDM). Pregnant women attending 131 prenatal clinics across India for the first time underwent SSP consisting of administration of 75 goral glucose irrespective of the last meal timing and to diagnose GDM with 2 h plasma glucose (PG) value >=7.8 mmol/L (7.8 mmol/L). RESULTS: In a cohort of n = 11,785, the number of pregnant women who underwent the test in first, second, and third trimesters were 4300, 4632, and 2853, respectively. Documented blood glucose values were available for 9282 pregnant women and in them, diagnosis of GDM was made in 740 (8%). Among them, 233 (31.5%), 320 (43.2%), and 187 (25.3%) were in the first, second and third trimesters, respectively. Positive family history of diabetes (43%) and history of fetal loss in previous pregnancy (27%) was more common in women diagnosed with GDM in the first trimester compared to GDM diagnosed in the second or third trimester. CONCLUSION: Manifestation of GDM in the early weeks of gestation is quite common. PMID- 26904468 TI - Dietary fat intake and its association with risk of selected components of the metabolic syndrome among rural South Indians. AB - CONTEXT: There is limited literature on the dietary fat intake of rural Indian populations, particularly in relation to the risk of metabolic syndrome (MS). AIM: This study aims to assess the dietary fat intake and analyze its association with the risk of selected components of the MS among rural population in the state of Tamil Nadu. SETTINGS AND DESIGN: Adults (n = 27012) >=20 years of age were recruited from the rural component of the Chennai Urban Rural Epidemiological Study, a cross-sectional study conducted in 42 villages in Kanchipuram District of Tamil Nadu. SUBJECTS AND METHODS: Using a validated food frequency questionnaire, data were obtained on the fat intake among 6907 adults. Anthropometric and clinical measures were collected using standard methods. The components of the MS assessed were abdominal obesity, hypertension, and impaired fasting glucose. All analyses were performed using SPSS software (version 20). RESULTS: Prevalence of abdominal obesity, hypertension, and impaired fasting glucose were significantly higher in the highest quintile of fat intake (33%, P < 0.001; 39%, P = 0.04, and 23.3%, P = 0.003, respectively). Highest intake of fat was also significantly associated with risk of abdominal obesity (P < 0.001), hypertension (P = 0.04), and impaired fasting glucose (P = 0.01). Sunflower oil as the main cooking oil was significantly associated with a higher risk of these components of the MS (P for trend <0.001) compared to traditional oils and palmolein. CONCLUSIONS: Higher dietary fat was significantly associated with risk of components of the MS and use of sunflower oil as main cooking oil increased metabolic risk in rural South Indians. PMID- 26904469 TI - Surgery or no surgery: What works best for the kidneys in primary hyperparathyroidism? A study in a multi-ethnic Asian population. AB - INTRODUCTION: Whether parathyroidectomy is more beneficial to renal function when compared to medical therapy or observation in primary hyperparathyroidism (PHPT) is unclear. Neither has this premise been explored in non-Caucasian populations. The estimated glomerular filtration rate (eGFR) threshold below which parathyroid hormone (PTH) levels rise if at all in PHPT has also not been established. We determined if surgery was superior to medical therapy and observation in a multi ethnic Asian patient population with PHPT and whether there was an eGFR threshold below which PTH levels further increased in them. METHODS: Retrospective evaluation of patients with PHPT. RESULTS: There were 68.6% Chinese, 17.4% Malays, 10.7% Indians, and 3.3% Eurasians. The median (interquartile range) follow-up was 18.0 months (4.5-46.8). At last follow-up, eGFR in the surgical (80 +/- 30 ml/min) was higher than the medical (52 +/- 32 ml/min) or observation groups (48 +/- 33 ml/min); P < 0.01. This difference persisted after adjusting for age, gender, ethnicity, pre-intervention eGFR levels, nephrolithiasis, serum calcium, phosphate, urinary calcium, and duration of follow-up; P = 0.035. There was no definite eGFR level below which PTH values rose. CONCLUSION: Our study provides compelling evidence that in PHPT, surgery may be associated with a better renal outcome compared to medical management or observation. This has to be confirmed through prospective randomized controlled trials and the reasons for this finding have to be elucidated through functional and histological measures. The finding in our study of a lack of a specific eGFR threshold below which PTH levels further rose challenges the concept of a fixed renal threshold for secondary elevations of PTH in PHPT. PMID- 26904470 TI - Bone mineral density in young adult women with congenital adrenal hyperplasia. AB - BACKGROUND: There is equipoise regarding the status of bone mineral density (BMD) in patients with congenital adrenal hyperplasia (CAH), where patients need to be on long-term low-dose steroids. OBJECTIVE: We aimed to evaluate BMD at the hip, spine and forearm in women with CAH and compare it to healthy young adult women of the same age range. SUBJECTS AND METHODS: Fifteen adult women with CAH with age ranging from 18 to 40 years (mean +/- standard deviation = 27.5 +/- 6.2 years) underwent dual-energy X-ray absorptiometry along with laboratory evaluation. BMD at lumbar spine, hip, forearm along with T-scores were measured. Serum total calcium, phosphate, alkaline phosphatase, 25 hydroxy Vitamin D, intact parathyroid hormone, total testosterone, and dehydroepiandrosterone were assayed. History of any fractures in the past was taken. Fifteen healthy women in the same age range were taken as controls for comparison. RESULTS: The BMD at hip (0.85 +/- 0.02 g/cm(2)) in CAH was significantly lower as compared with controls (0.92 +/- 0.03 g/cm(2), P = 0.029). BMD at lumbar spine was also reduced (0.96 +/ 0.02 vs. 1.03 +/- 0.03, P = 0.057). The BMD at forearm was not significantly different between CAH and controls. The mean Vitamin D was 9.8 ng/ml (deficient range). There was no history of fractures in CAH. CONCLUSION: Young adult CAH women had lower BMD at spine and hip than healthy young adult women of the same age range. The forearm BMD was not different from controls. No change in fracture frequency was present. Patients with CAH being treated with steroids are at increased risk of osteopenia, and their bone health needs to be monitored. PMID- 26904471 TI - Comparison of efficacy and safety of choline fenofibrate (fenofibric acid) to micronized fenofibrate in patients of mixed dyslipidemia: A randomized, open label, multicenter clinical trial in Indian population. AB - INTRODUCTION: Choline fenofibrate is a newly developed choline salt of fenofibric acid, which is more hydrophilic than fenofibrate. This study was initiated to evaluate the safety and efficacy of choline fenofibrate in comparison to micronized fenofibrate among Indian patients of mixed dyslipidemia. METHODS: A multicenter, open-label, randomized, active controlled, comparative, parallel group study was conducted at around 10 centers spread all across the country. Mixed dyslipidemia patients (serum triglycerides [TG] levels between 150 and 500 mg/dl), aged 18-70 years and taking stable statin dose for 8 weeks were randomized to choline fenofibrate 135 mg delayed release tablets and micronized fenofibrate 160 mg tablets once daily for 12 weeks. The primary endpoint of the study was percentage change in serum TG level at the end of 12 weeks. RESULTS: A total of 226 patients were enrolled in this study, of which 116 patients were administered choline fenofibrate and 110 patients were administered micronized fenofibrate. At the end of 12 weeks, there was a significant reduction in TG level (34.24% in choline fenofibrate group and 38.13% reduction in micronized fenofibrate group). However, the difference between group was not statistically different (P = 0.471). Similarly, there was a significant increase in high density lipoprotein cholesterol at the end of 12 weeks (10% increase in choline fenofibrate group and 9% increase in micronized fenofibrate group); but the difference between the group was not statistically significant (P = 0.598). Both the treatment was safe and well tolerated. CONCLUSION: Choline fenofibrate delayed release 135 mg is as safe and effective as 160 mg of micronized fenofibrate in Indian patients with mixed dyslipidemia. PMID- 26904472 TI - Assessment of serum prolactin levels in acute myocardial infarction: The role of pharmacotherapy. AB - BACKGROUND: Hyperprolactinemia may reflect neuroendocrine stress reaction against acute coronary syndromes. AIM: The aim of the present study was evaluation of the serum prolactin level in the acute myocardial infarction (MI) regarding the current pharmacotherapy in management of MI. SETTING AND DESIGN: Cross-sectional clinical based study. SUBJECTS AND METHODS: This cross-sectional clinical study involved all patients with acute MI in a coronary care unit, a total number of 44 patients (45% males and 55% females) with age ranged from 40 to 75 years. A full history for modifiable risk factors and current therapy with aspirin, clopidogrel and or metformin, all patients are nonsmokers. The anthropometric measurements; for estimations of body mass index (kg/m(2)), electrocardiography was obtained. Fasting blood samples were taken in the morning from all patients and the sera used for estimations of routine investigation and determination of ischemic cardiac biomarkers like cardiac troponin I (cTnI) and serum prolactin level. RESULTS: This study shows a significant increase in the serum prolactin in acute MI as compared with the control. In acute MI serum cTnI elevation was correlated with serum prolactin increments. In metformin-treated group, there was a lowest prolactin serum level. CONCLUSIONS: Serum prolactin level increased in acute MI, and positively correlated with cardiac troponin level and reflects underlying cardiovascular complications. PMID- 26904473 TI - Primary hyperparathyroidism: A changing scenario in India. AB - INTRODUCTION: Primary hyperparathyroidism (PHPT) is largely a symptomatic disease with varied systemic manifestations, complicated by coexisting Vitamin D (Vit D) deficiency. Increasing awareness, developments in diagnostics, and Vit D supplementation may have an impact on the disease profile of PHPT. METHODS: Clinical, biochemical, and pathological profile of PHPT presenting to a tertiary care center in South India were compared in two groups separated as per the period of presentation (Group A: January 1994-May 2007 - 51 cases and Group B: June 2007-January 2015 - 59 cases). RESULTS: PHPT has remained a disease of female preponderance with similar age of presentation. It is being diagnosed earlier (mean duration of symptoms prior to diagnosis was 38.7 months in Group A, significantly longer than 26 months in Group B). Bone pain and metabolic myopathy were the most common presentations (60%) followed by pathological fracture (16%), renal calculi (13%), and pancreatitis (7%). Pathological fractures have become less frequent. Vit D deficiency is still a widespread co-morbidity. Radionuclide scintigraphy is an effective localizing tool, but ultrasound can be an inexpensive and widely available screening modality. CONCLUSION: PHPT still remains asymptomatic disease of bones and stones, although it is being diagnosed early. Greater awareness, Vit D supplementation, and better diagnostic tools have made it a disease with lesser morbidity and effective cure. PMID- 26904474 TI - Chronic sub-clinical inflammation in the abdominal adipose tissue - Evaluation of inflammatory cytokines and their link with insulin resistance in metabolically obese South Indians: A cross-sectional observational study. AB - OBJECTIVE: To measure the levels of proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin-6(IL-6), and high-sensitive C-reactive protein (hs-CRP) and the anti-inflammatory cytokine adiponectin (AN) in obese South Indian subjects and to ascertain whether or not a causal role could be ascribed to these cytokines in the development of insulin resistance (IR). MATERIALS AND METHODS: Forty obese and forty nonobese volunteers of both genders were recruited. Parameters such as body mass index (BMI), waist circumference (WC), and blood pressure were evaluated. Fasting blood sugar (FBS), fasting insulin level, hemoglobin A1c (HbA1C), lipid profile, TNF-alpha, IL-6, hs-CRP, and AN levels were measured. IR was evaluated by homeostatic model assessment-IR method. Abdominal adiposity was measured by ultrasonography. The results were statistically evaluated by appropriate tests. RESULTS: BMI, WC, and visceral fat were high in the obese group. Females had higher subcutaneous fat in both groups. HbA1C was marginally high in the obese group (P = 0.014). IR was high in all the groups, obese males showing higher values (not significant[NS]). Total cholesterol and low-density lipoprotein were high in the obese group (P = 0.028, P = 0.003). TNF-alpha was high in obese males (NS), IL-6 was high in both groups, higher in nonobese females (NS), hs-CRP was high in both groups, higher in females of both groups (NS). AN was high in females of both groups (P = 0.002). CONCLUSIONS: In this study on South Indian subjects, proinflammatory cytokines such as IL-6 and hs-CRP, despite being high, did not show any causal correlation either with abdominal obesity or with IR. TNF-alpha being normal showed some correlation which was inconsistent. Even the anti-inflammatory adipokine, AN did not show any correlation with IR. Cytokines had an inconsistent correlation with the components of metabolic syndrome hence were not useful. PMID- 26904475 TI - Cross-sectional study of serum parathyroid hormone level in high-risk pregnancies as compared to nonpregnant control. AB - OBJECTIVES: To note the value of serum parathyroid hormone (PTH) levels in normal and high-risk pregnancies (HRP) in patients attending antenatal visits at All India Institute of Medical Sciences (AIIMS). MATERIALS AND METHODS: This is a cross-sectional study where a total of 282 patients attending Gynecology Outpatient Department at AIIMS, New Delhi were recruited. Among the 282 subjects, 251 were pregnant, and 31 were controls. The serum was tested for serum PTH levels using Beckman coulter access 2 immunoassay. RESULTS: The median value of PTH level in pregnant women was 31.6 pg/ml with range being 0.8-505.5 pg/ml in contrast to 45.9 pg/ml with range being 19-102.7 pg/ml in nonpregnant female. This difference was statistically significant (P = 0.0012). There was no significant difference in median level of PTH in different age group. Although the median PTH levels were lower in second trimester (25.25 pg/ml) than in first trimester (35.5 pg/ml) and in third trimester (32.4 pg/ml), the difference was not statistically significant. There was no significant difference in PTH level in HRP (median value - 31.6 pg/ml) as compared to low-risk pregnancies (31.5 pg/ml). CONCLUSION: Serum PTH levels are significantly lower during pregnancy as compared to nonpregnant state. However, age, parity, and HRP did not alter PTH level during pregnancy. PMID- 26904476 TI - Celiac autoimmunity in autoimmune thyroid disease is highly prevalent with a questionable impact. AB - INTRODUCTION: The prevalence of autoimmune thyroid disease (AITD) is 10-12% in the general population worldwide. Among various disorders co-existing with AITD, the concomitance of celiac disease (CD) with AITD results in poor absorption of thyroid medications and results in higher doses of the same. Institution of gluten-free diet (GFD) in this cohort helps reduce medication doses. AIM: To screen patients with AITD for the presence of celiac autoimmunity (CA). MATERIALS AND METHODS: A total of 280 consecutive patients with AITD attending the thyroid Out-patient Department of a tertiary care hospital were screened for the presence of tissue transglutaminase antibodies (immunoglobulin A tissue transglutaminase). Those with a positive titer (but < 10 times the upper limit of normal) underwent upper gastrointestinal endoscopy and duodenal mucosal biopsy for the diagnosis of CD, followed by institution of GFD in confirmed cases. RESULTS: Of a total of 280 (182 females and 98 males) patients with AITD screened, 24 (8.6%) turned out to be positive for CA. Of 24 (8.6%), 15 (8.24%) females and 9 (9.18%) males were positive for CA. There was no statistically significant difference in the thyroxine doses required for normalization of thyroid function and the weight of the patients in CA positive and CA negative patients. CONCLUSIONS: The prevalence of CD in patients with AITD is much greater than in the general population. This forms the basis for screening patients with AITD for presence of CD. PMID- 26904477 TI - Trimester specific reference intervals for thyroid function tests in normal Indian pregnant women. AB - CONTEXT: Accurate assessment of thyroid function during pregnancy is critical, for initiation of thyroid hormone therapy, as well as for adjustment of thyroid hormone dose in hypothyroid cases. AIMS: We evaluated pregnant women who had no past history of thyroid disorders and studied their thyroid function in each trimester. SETTINGS AND DESIGN: 86 normal pregnant women in the first trimester of pregnancy were selected for setting reference intervals. All were healthy, euthyroid and negative for thyroid peroxidase antibody (TPOAb). These women were serially followed throughout pregnancy. 124 normal nonpregnant subjects were selected for comparison. MATERIAL AND METHODS: Thyrotropin (TSH), free thyroxine (FT4), free triiodothyronine (FT3) and anti-TPO were measured using Roche Elecsys 1010 analyzer. Urinary iodine content was determined by simple microplate method. The 2.5th and 97.5th percentiles were calculated as the reference intervals for thyroid hormone levels during each trimester. STATISTICAL ANALYSIS: SPSS (version 14.0, SPSS Inc., Chicago, IL, USA) was used for data processing and analysis. RESULTS: The reference intervals for the first, second and third trimesters for the following parameters: TSH 0.09-6.65, 0.51-6.66, 0.91-4.86 uIU/mL, FT4 9.81 18.53, 8.52-19.43, 7.39-18.28 pM/L and FT3 3.1-6.35, 2.39-5.12, 2.57-5.68 pM/L respectively. Thyroid hormone concentrations significantly differed during pregnancy at different stages of gestation. The pregnant women in the study had median urinary iodine concentration of 150-200 ug/l during each trimester. CONCLUSIONS: The trimester-specific reference intervals for thyroid tests during pregnancy have been established for pregnant Indian women serially followed during pregnancy using 2.5th and 97.5th percentiles. PMID- 26904479 TI - Cardiovascular risk factors, micro and macrovascular complications at diagnosis in patients with young onset type 2 diabetes in India: CINDI 2. AB - CONTEXT: Type 2 diabetes mellitus (T2DM) in young adults is increasing in India. Data on the prevalence of cardiovascular (CV) risk factors and complications associated with young-onset T2DM (YOD) at the time of diagnosis of diabetes are limited. This data can aid in aggressive diabetes management, CV risk reduction, and prevention of complications. AIM: To determine the prevalence of CV risk factors, micro and macrovascular complications in patients with newly diagnosed YOD. To assess the percentage of patients who require statin therapy based on current American Diabetes Association (ADA) guidelines. SETTINGS AND DESIGN: This was a retrospective cross-sectional study of 1500 patients with newly detected YOD across seven centers from 2013 to 2015. DESIGNS AND METHODS: Patients were evaluated for complications of diabetes and CV risk factors such as body mass index (BMI), hypertension, dyslipidemia, and smoking. STATISTICAL ANALYSIS: Measurements have been presented as mean +/- standard deviation; results on categorical measurements have been presented in percentages. RESULTS: The mean age, glycated hemoglobin and BMI were 34.7 +/- 4.2 years, 9.9 +/- 2.4%, and 26.8 +/- 4.7 kg/m(2). Hypertension, dyslipidemia, BMI >23 kg/m(2), and smoking were presented in 27.6%, 62.4%, 84.2%, and 24%. Diabetic retinopathy, neuropathy, and nephropathy were seen in 5.1%, 13.2%, and 0.9%. Ischemic heart disease, peripheral vascular disease, and stroke were presented in 0.7%, 2%, and 0.1%. As per current guidelines, 95.33% needed statin therapy. CONCLUSION: This study demonstrates that patients with YOD have micro and macrovascular complications at diagnosis. Nearly, every patient required a statin to reduce CV risk. This highlights the importance of screening patients with YOD for CV risk factors and complications of diabetes at the time of diagnosis. PMID- 26904478 TI - Effect of hypothyroidism on female reproductive hormones. AB - OBJECTIVE: Objective was to evaluate reproductive hormones levels in hypothyroid women and impact of treatment on their levels. MATERIALS AND METHODS: A total of 59 women with untreated primary hypothyroidism were included in this prospective study. Venous blood was taken at baseline and after euthyroidism was achieved for measuring serum free thyroxine, free triiodothyronine (FT3), thyroid stimulating hormone (TSH), prolactin (PRL), follicular stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), testosterone (T), and thyroid peroxidase antibody. Thirty-nine healthy women with regular menstrual cycles without any hormonal disturbances served as controls. The statistical analysis was performed using the Statistical Package for the Social Sciences Version 20 ([SPSS] IBM Corporation, Armonk, NY, USA). P < 0.05 was considered statistically significant. RESULTS: On an average at diagnosis cases have more serum TSH (mean [M] = 77.85; standard error [SE] = 11.72), PRL (M = 39.65; SE = 4.13) and less serum E2 (M = 50.00; SE = 2.25) and T (M = 35.40; SE = 2.31) than after achieving euthyroidism (M = 1.74; SE = 0.73), (M = 16.04; SE = 0.84), (M = 76.25; SE = 2.60), and (M = 40.29; SE = 2.27), respectively. This difference was statistically significant t (58) = 6.48, P <0.05; t (58) = 6.49, P < 0.05; t (58) = 12.47; P < 0.05; and t (58) = 2.04, P < 0.05; respectively. Although average serum FSH (M = 12.14; SE = 0.40) and LH (M = 5.89; SE = 0.27) were lower in cases at diagnosis than after achieving euthyroidism (M = 12.70; SE = 0.40), (M = 6.22; SE = 0.25), respectively, but these differences were statistically insignificant t (58) = 1.61, P = 0.11; t (58) = 1.11, P = 0.27, respectively. CONCLUSION: The study has demonstrated low E2 and T levels in hypothyroid women which were increased after achieving euthyroidism. Although average serum FSH and LH were increased in hypothyroid women after achieving euthyroidism but this difference was statistically insignificant. PMID- 26904480 TI - Goiter in portraits of Judith the Jewish heroine. AB - Judith was a legendary Hebrew heroine who beheaded the general Holofernes and saved the children of Israel from destruction by the Assyrian army. In the Book of Judith, which is still present in the Catholic and Orthodox Christian Bibles, Judith is presented as an illustrious woman who defeated the enemy using her virtue and fortitude. The present investigation has revealed 24 portraits in which Judith has been depicted with variable grades of thyroid gland enlargement on the scene where she decapitates Holofernes. There is no doubt that the integration of a slight thyroid enlargement in the paintings is a stylistic hallmark that portrays an idealized female beauty with a balanced neck and graceful body. The large extended goiter was probably depicted by the artists as a symbol of a powerful masculine body and her courage, and at the same time, it probably also reflects better anatomic accuracy and knowledge of artists from that period. PMID- 26904481 TI - Arjuna's recollections - Part III (or) an endocrine version of the "Motorcycle Diaries". AB - The ultimate dream of every young student stepping into the hallowed portals of a medical college is to achieve the holy grail of medical education, a DM seat. However, the real battle begins only after the DM seat is won. The residency is a veritable roller coaster ride all through the three years, with the student alternating between exhilaration and despondency, wisdom and foolishness, hope and despair and ecstasy and agony. The long working hours, logistic difficulties, interpersonal conflicts and resource limitations are the anvils on which the callow postgraduates are beaten into shape, to bring to fore, their inner steel. While the DM residency does succeed in shaping the students into capable and empathic healthcare professionals of the highest order, on quite a few occasions, it leaves behind a host of bittersweet memories, that prompt the student to look back often, not with fondness, but with a sense of regret and heartache. Encompassing all these experiences, is an unvarnished first-hand account of my peregrinations as an endocrine resident at Osmania Medical College. PMID- 26904482 TI - Presentation of gender dysphoria: A perspective from Eastern India. AB - CONTEXT: There is paucity of scientific data from India on gender identity disorders (GIDs) or gender dysphoria (GD). AIMS: To study the clinical, biochemical profile, personality characteristics and family support of GID subjects. SETTINGS AND DESIGN: A retrospective and cross-sectional study at an endocrine referral center in Kolkata in Eastern India between 2010 and 2015. SUBJECTS AND METHODS: Seventy-three GID subjects who presented to the center were included in the study. Clinical, biochemical profile, personality characteristics (cross-dressing), and family support were investigated. The protocol was presented to the Ethics Committee who felt that given the retrospective nature of the study, informed consent could be dispensed with. GD was diagnosed by Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition). STATISTICAL ANALYSIS USED: Unpaired t-test has been used to find the significance of study parameters between two groups of patients. Chi-square/Fisher Exact test has been used to find the significance of study parameters on categorical scale between two groups. RESULTS: Out of the total 73 patients, 55 (75.34%) patients were male-to-female and remaining 18 (24.66%) were female-to-male. Around 11% of GD subjects practiced cross-dressing. In spite of median age of onset of GD was 9 years, the mean age of GD at presentation was quite late at 25.77 +/- 6.25 years due to lack of social and informative support. It is difficult for transgender to express their sexual identity in family or in society as only 10.96% of our GD subjects had family support, leading to delayed presentation and delayed endocrine consultation. This delayed endocrine consultation have accounted for a significant proportion of GD subjects having unplanned and ill-timed castration (16.36%) or mastectomy (16.67%) even by nonmedically qualified person (66.7% of castrated subjects). All GD subjects had normal thyroid stimulating hormone, testosterone, estradiol, and karyotype concordant with their biological sex. No significant differences were demonstrated between any of the studied parameters namely age at presentation, onset-age of GD, hormone profile, family support, and cross-dressing preferences. CONCLUSIONS: Social taboo and lack of informative, family support leads to delayed medical consultation and have accounted for complexities in presentation indicating a huge need of awareness programs in our country. Social and informative support can be improved by awareness programs, which might lead to an early endocrine evaluation and proper treatment with improved outcomes. PMID- 26904483 TI - Endocrine hygiene. PMID- 26904484 TI - Short-term outcomes of type 2 diabetes mellitus patients treated with canagliflozin in real-world setting. AB - OBJECTIVE: This study is aimed to evaluate the characteristics, treatment, and outcomes of patients treated with canagliflozin in the real-world setting within the first 4 months of the product's availability in India. PATIENTS AND METHODS: It is a retrospective study with data collected from Indian clinical database. Patients aged 18 and above who were prescribed canagliflozin were included in this study. All the patients were on other antihyperglycemic agents (AHAs) before the initiation of canagliflozin. RESULTS: Overall, nine patients were included in the study, and data for these patients with mean duration of follow-up of 16 weeks was analyzed. Mean age was 47.9 years and mean duration of type 2 diabetes was 6.7 years. Among patients with available laboratory data at baseline and follow-up, mean glycosylated hemoglobin A1c (HbA1c) decreased from 9.0% at baseline to 6.8% at follow-up (P < 0.005); mean weight reduced from 69.9 kg at baseline to 67.9 kg at follow-up. When compared to baseline, the usage and or dose of other AHAs were reduced during follow-up. CONCLUSION: Canagliflozin after it became available in India, improved all glycemic parameters and also reduced the weight of the type two diabetic patients who were poorly controlled by multiple AHAs. PMID- 26904485 TI - Newer antidiabetic drugs and calorie restriction mimicry. AB - De-acceleration of aging and delayed development of age-related morbidity accompanies the restriction of calories (without malnutrition) in laboratory mice, nematodes, yeast, fish, and dogs. Recent results from long-term longitudinal studies conducted on primates have suggested longevity benefits of a 30% restriction of calories in rhesus monkeys as well. Among calorie restricted rhesus monkeys one of the mechanisms for the improvement in lifespan was the reduction in the development of glucose intolerance and cardiovascular disease. Although there are no comparable human studies, it is likely that metabolic and longevity benefits will accompany a reduction in calories in humans as well. However, considering the difficulties in getting healthy adults to limit food intake science has focused on understanding the biochemical processes that accompany calorie restriction (CR) to formulate drugs that would mimic the effects of CR without the need to actually restrict calories. Drugs in this emerging therapeutic field are called CR mimetics. Some of the currently used anti-diabetic agents may have some CR mimetic like effects. This review focuses on the CR mimetic properties of the currently available anti-diabetic agents. PMID- 26904487 TI - Editor-in-Chief should not neglect case reports. PMID- 26904486 TI - Turmeric use is associated with reduced goitrogenesis: Thyroid disorder prevalence in Pakistan. PMID- 26904488 TI - Low-level laser therapy affects osseointegration in titanium implants: resonance frequency, removal torque, and histomorphometric analysis in rabbits. AB - OBJECTIVES: The purpose of this study was to investigate the effects of low-level laser therapy (LLLT) with a diode gallium-aluminum-arsenide (Ga-Al-As) low-level laser device on the healing and attachment of titanium implants in bone. MATERIALS AND METHODS: Thirteen New Zealand white male rabbits weighing 3.0+/-0.5 kg were used for this study. Dental titanium implants (3.75 mm in diameter and 8.5 mm in length, US II RBM plus fixture; Osstem, Seoul, Korea) were implanted into both femurs of each rabbit. The rabbits were randomly divided into a LLLT group and a control group. The LLLT was initiated immediately after surgery and then repeated daily for 7 consecutive days in the LLLT group. Six weeks and 12 weeks after implantation, we evaluated and compared the osseointegration of the LLLT group and control group, using histomorphometric analysis, removal torque testing, and resonance frequency analysis (RFA). The results were statistically significant when the level of probability was 0.05 or less based on a non parametric Mann-Whitney U-test. RESULTS: The implant survival rate was about 96%. Histologically and histomorphometrically, we observed that the titanium implants were more strongly attached in LLLT group than in control group. However, there was no significant difference between the LLLT group and control group in removal torque or RFA. CONCLUSION: Histologically, LLLT might promote cell-level osseointegration of titanium implants, but there was no statistically significant effects. PMID- 26904489 TI - The effect of low-speed drilling without irrigation on heat generation: an experimental study. AB - OBJECTIVES: In this study we evaluated heat generation during the low-speed drilling procedure without irrigation. MATERIALS AND METHODS: Ten artificial bone blocks that were similar to human D1 bone were used in this study. The baseline temperature was 37.0C. We drilled into 5 artificial bone blocks 60 times at the speed of 50 rpm without irrigation. As a control group, we drilled into an additional 5 artificial bone blocks 60 times at the speed of 1,500 rpm with irrigation. The temperature changes during diameter 2 mm drilling were measured using thermocouples. RESULTS: The mean maximum temperatures during drilling were 40.9C in the test group and 39.7C in the control group. Even though a statistically significant difference existed between the two groups, the low speed drilling did not produce overheating. CONCLUSION: These findings suggest that low-speed drilling without irrigation may not lead to overheating during drilling. PMID- 26904490 TI - Management of maxillofacial injuries in bear mauling cases: a review of 20 cases. AB - OBJECTIVES: As the craniofacial and neck regions are prime areas of injury in bear attacks, the careful management of soft and hard tissue injuries and selection of reconstructive options is of the utmost importance. This study will review the incidence and patterns of bear mauling in eastern India reported to our department and the various modalities used for their treatment over a period of 7 years. It also documents the risks of infection in bear mauling cases and the complications that have occurred. MATERIALS AND METHODS: Twenty cases were treated over the study period. Cases were evaluated for soft and hard tissue injuries including tissue loss and corresponding management in the craniofacial region. Cases were also evaluated for other associated injuries, organ damage and related complications. RESULTS: Various modalities of treatment were used for the management of victims, ranging from simple primary repairs to free tissue transfers. Simple primary repairs were done in 75% of cases, while the management of the injured victims required reconstruction by local, regional or distant flaps in 25%. Free tissue transfers were performed in 15% of cases, and no cases of wound infection were detected in the course of treatment. CONCLUSION: Knowledge of various reconstructive techniques is essential for managing maxillofacial injuries in bear mauling cases. Modern reconstructive procedures like free tissue transfer are reliable options for reconstruction with minimal co morbidity and dramatic improvement in treatment outcomes. PMID- 26904491 TI - Investigation of a pre-clinical mandibular bone notch defect model in miniature pigs: clinical computed tomography, micro-computed tomography, and histological evaluation. AB - OBJECTIVES: To validate a critical-size mandibular bone defect model in miniature pigs. MATERIALS AND METHODS: Bilateral notch defects were produced in the mandible of dentally mature miniature pigs. The right mandibular defect remained untreated while the left defect received an autograft. Bone healing was evaluated by computed tomography (CT) at 4 and 16 weeks, and by micro-CT and non decalcified histology at 16 weeks. RESULTS: In both the untreated and autograft treated groups, mineralized tissue volume was reduced significantly at 4 weeks post-surgery, but was comparable to the pre-surgery levels after 16 weeks. After 16 weeks, CT analysis indicated that significantly greater bone was regenerated in the autograft treated defect than in the untreated defect (P=0.013). Regardless of the treatment, the cortical bone was superior to the defect remodeled over 16 weeks to compensate for the notch defect. CONCLUSION: The presence of considerable bone healing in both treated and untreated groups suggests that this model is inadequate as a critical-size defect. Despite healing and adaptation, the original bone geometry and quality of the pre-injured mandible was not obtained. On the other hand, this model is justified for evaluating accelerated healing and mitigating the bone remodeling response, which are both important considerations for dental implant restorations. PMID- 26904492 TI - Changes in the management and survival rates of patients with oral cancer: a 30 year single-institution study. AB - OBJECTIVES: The aim of the present study was to evaluate changes in the management and 5-year survival rates of patients with oral cancer in our department over a 30-year period. MATERIALS AND METHODS: We investigated the patient distributions, treatment methods, method of neck dissection according to cancer stage, and 5-year survival rates for 700 oral cancer patients over the periods of 1982-1996 (256 patients), 1999-2006 (248 patients), and 2007-2011 (196 patients). RESULTS: Stage IV patients were the largest group in all of the time periods evaluated. Although surgery and radiotherapy were the most common methods in all periods (over 50%), the prevalence of patients who underwent concomitant chemoradiotherapy increased from 7.0% to 16.2%. The use of radical neck dissection decreased from 43.0% to 5.3%, while conservative surgical methods increased from 24.1% to 76.3%. Lastly, the overall 5-year survival rate increased from 31.6% to 63.5% during the study period. CONCLUSION: Although the 5-year survival rate reached the same level as that of other developed countries during the course of our study, most patients continue to come to the hospital with stage IV disease. In order to increase the 5-year survival rate of oral carcinoma, it may be necessary to improve public education and social efforts relevant to early diagnosis. PMID- 26904493 TI - Histologic analysis of resorbable blasting media surface implants retrieved from humans: a report of two cases. AB - The purpose of this study is to evaluate the degree of osseointegration of resorbable blasting media (RBM) surface implants retrieved from humans. Three implants in the mandibular molar region that were surface-treated with RBM were retrieved from two patients. The implants were used to manufacture specimens in order to measure the bone-implant contact (BIC) ratio. The BIC ratios of the three implants were found to be an average of 69.0%+/-9.1%. In conclusion, that RBM surface implants are integrated into the host environment with histological significance and the BIC ratio of the RBM surface-treated implant was not significantly different from that of other surface-treated implants. PMID- 26904494 TI - Ameloblastic carcinoma of the maxilla: a report of two cases and a review of the literature. AB - Ameloblastic carcinoma is a malignant form of ameloblastoma defined by histological evidence of malignancy in primary, recurrent, or metastatic tumor. Such a tumor is rare, and the maxilla is an unusual site. Due to its rarity, the characteristics of this tumor in the maxilla have not been well described. Case 1: A 55-year-old, ill-appearing Nigerian male presented to our center with left maxillary swelling of seven-year duration. The swelling had been slow-growing and painless until one year prior, when the growth became rapid and was coupled with severe pain. The swelling affected both oral function and facial esthetics, and the patient reported difficulty breathing. There was a maxillary, ulcerated swelling extending from teeth 12 to 18 and blocking the left nostril. The involved teeth were moderately mobile. Case 2: A 32-year-old male farmer presented with recurrent right maxillary swelling of six-year duration. Prior to this episode, he had undergone surgery for ameloblastoma (follicular type). The present swelling was fungating through the skin and protruding into the right nostril. Ameloblastic carcinoma is an aggressive odontogenic tumor that requires aggressive surgical treatment. PMID- 26904495 TI - Tongue-lip adhesion in Pierre Robin sequence. AB - Patients with Pierre Robin sequence exhibit varying degrees of airway obstruction and feeding difficulty. In some patients, airway obstruction may be profound, warranting surgical intervention to maintain a patent airway. The purpose of this article is to highlight the advantages of the tongue-lip adhesion procedure for the management of airway obstruction in such patients compared to the currently available options. PMID- 26904496 TI - Anterior tympanic plate fracture following extraction of the lower molar. AB - The present case report describes an external auditory canal injury following extraction of the lower molar. The external auditory canal was torn in the same fashion that occurs in an anterior tympanic plate fracture. This case demonstrates one of the rare complications associated with dental extractions. PMID- 26904497 TI - Myositis ossificans of the platysma mimicking a malignancy: a case report with review of the literature. AB - The two main forms of myositis ossificans are congenital and acquired. Either form is rare in the head and neck region. The acquired form is often due to trauma, with bullying as a fairly common cause. This report of myositis ossificans of the platysma in an 11-year-old female patient emphasizes the need for a high index of suspicion in unexplainable facial swellings in children and the benefit of modern investigative modalities in their management. PMID- 26904498 TI - Neurilemmoma in the floor of the mouth: a case report. AB - Neurilemmomas are well-encapsulated, benign, slow-growing tumors originating from Schwann cells of the nerve sheath surrounding cranial, peripheral, or autonomic nerves. Intraoral neurilemmomas are relatively rare and have a wide variety of morphologic and radiologic features. This makes differential diagnosis difficult, and only histopathological features can lead to a definitive neurilemmoma diagnosis. In this report, we present the case of a 30-year-old woman whose chief complaint was a solitary, nodular mass on the right floor of the mouth. After computed tomography and magnetic resonance imaging, we performed an incisional biopsy that showed the typical characteristics of a neurilemmoma. The mass was removed completely through an intraoral surgical approach. Despite losing a portion of the lingual nerve, the patient did not complain of any specific discomfort. Wound healing was uneventful and there were no signs or symptoms of recurrence. PMID- 26904499 TI - The Significance of a Common Idiotype (1F7) on Antibodies against Human Immune Deficiency Virus Type 1 and Hepatitis C Virus. AB - In this review, we trace the concept and potential functional role of regulatory idiotypes in the immune response to human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus, and hepatitis C virus (HCV). A major idiotype involved in these viral infections is recognized and defined by a murine monoclonal antibody (1F7). Antibodies expressing the idiotype defined by 1F7 are dominant in HIV-1 infection and are also found on many broadly neutralizing antibodies against HIV-1. This regulatory idiotypic axis offers opportunities for exploitation in vaccine development for HIV-1, HCV, and other chronic viral infections. PMID- 26904500 TI - A Review of Radiotherapy-Induced Late Effects Research after Advanced Technology Treatments. AB - The number of incident cancers and long-term cancer survivors is expected to increase substantially for at least a decade. Advanced technology radiotherapies, e.g., using beams of protons and photons, offer dosimetric advantages that theoretically yield better outcomes. In general, evidence from controlled clinical trials and epidemiology studies are lacking. To conduct these studies, new research methods and infrastructure will be needed. In the paper, we review several key research methods of relevance to late effects after advanced technology proton-beam and photon-beam radiotherapies. In particular, we focus on the determination of exposures to therapeutic and stray radiation and related uncertainties, with discussion of recent advances in exposure calculation methods, uncertainties, in silico studies, computing infrastructure, electronic medical records, and risk visualization. We identify six key areas of methodology and infrastructure that will be needed to conduct future outcome studies of radiation late effects. PMID- 26904501 TI - Analysis of Prognostic Factors in High-Grade Osteosarcoma of the Extremities in Children: A 15-Year Single-Institution Experience. AB - BACKGROUND: The aim of this retrospective study was to define clinical and pathological features and prognostic factors among children and adolescents diagnosed with high-grade osteosarcoma of the extremities. METHODS: A total of 73 patients younger than 18 years diagnosed with primary osteosarcoma of the extremities between January 1998 and December 2013 were retrospectively evaluated. Prognostic factors, such as age, gender, primary tumor site, alkaline phosphatase and lactate dehydrogenase levels, metastatic disease, pathological fracture, histological response, and surgery type, were analyzed to evaluate their effects on overall survival (OS) and event-free survival (EFS). RESULTS: At a median follow-up of 30 months (1.5-152), OS and EFS at 5 years were 64.5 +/- 8.1 and 48.5 +/- 8.7% for patients with localized disease; and 16.2 +/- 7.9 and 14.4 +/- 7.3% for patients with initial metastatic disease, respectively. In patients with localized disease, conservative surgery was performed on 22 of 46 patients (43.5%), and there was no significant difference in survival rates among patients who had conservative vs. radical surgery (p = 0.65). Although tumor size (>12 cm) was significant prognostic factor in univariate analysis; multivariate analysis identified elevated levels of alkaline phosphatase (p = 0.033) and poor response to neoadjuvant chemotherapy (p < 0.001) only as independent prognostic factors. Age, histological type, pathological fracture, and primary tumor site did not significantly affect prognosis. CONCLUSION: Initial elevated presence of alkaline phosphatase in serum and poor histological response after neoadjuvant chemotherapy were significant factors for unfavorable prognosis. It is necessary to optimize staging and treatment intensification to improve survival rates, especially among patients with metastasis at initial presentation. PMID- 26904503 TI - The Value of Ultrasound Monitoring of Adnexal Masses for Early Detection of Ovarian Cancer. AB - Although ultrasound has so far been found to be ineffective as a screening tool for ovarian cancer, it is commonly used as a means of evaluating or following ovarian or adnexal masses once they are detected. We review the use of serial ultrasound for the management of adnexal masses and propose an approach to monitoring based on an understanding of the overall risk of cancer among the population in question and an assessment of how the potential benefit of monitoring compares with potential risk. In our approach, masses that are symptomatic, large (>10 cm), associated with an elevated CA 125 level or overt signs of malignancy, or that are determined to have a worrisome appearance by stringent ultrasound criteria should be evaluated surgically. Women with masses that have none of these characteristics should be offered monitoring. Short-term initial ultrasound monitoring carries significant potential benefit in terms of aiding detection of early malignancy and avoidance of unnecessary surgery. However, if a mass remains stable but persistent, the potential benefit of ongoing monitoring wanes with time, whereas the potential harms, in terms of patient anxiety, cost, and the risk of incidental findings and unnecessary surgery increase. Therefore, monitoring of stable lesions should be limited in duration in order to limit potential harms from overtreatment and overdiagnosis. PMID- 26904504 TI - Plan Quality and Treatment Efficiency for Radiosurgery to Multiple Brain Metastases: Non-Coplanar RapidArc vs. Gamma Knife. AB - OBJECTIVES: This study compares the dosimetry and efficiency of two modern radiosurgery [stereotactic radiosurgery (SRS)] modalities for multiple brain metastases [Gamma Knife (GK) and LINAC-based RapidArc/volumetric modulated arc therapy], with a special focus on the comparison of low-dose spread. METHODS: Six patients with three or four small brain metastases were used in this study. The size of targets varied from 0.1 to 10.5 cc. SRS doses were prescribed according to the size of lesions. SRS plans were made using both Gamma Knife((r)) Perfexion and a single-isocenter, multiple non-coplanar RapidArc((r)). Dosimetric parameters analyzed included RTOG conformity index (CI), gradient index (GI), 12 Gy isodose volume (V 12Gy) for each target, and the dose "spread" (Dspread) for each plan. Dspread reflects SRS plan's capability of confining radiation to within the local vicinity of the lesion and to not spread out to the surrounding normal brain tissues. Each plan has a dose (Dspread), such that once dose decreases below Dspread (on total tissue dose-volume histogram), isodose volume starts increasing dramatically. Dspread is defined as that dose when volume increase first exceeds 20 cc/0.1 Gy dose decrease. RESULTS: RapidArc SRS has smaller CI (1.19 +/- 0.14 vs. 1.50 +/- 0.16, p < 0.001) and larger GI (4.77 +/- 1.49 vs. 3.65 +/- 0.98, p < 0.01). V 12Gy results were comparable (2.73 +/- 1.38 vs. 3.06 +/- 2.20 cc, p = 0.58). Moderate to lower dose spread, V6, V4.5, and V3, were also equivalent. GK plans achieved better very low-dose spread (<=3 Gy) and also had slightly smaller Dspread, 1.9 vs. 2.5 Gy. Total treatment time for GK is estimated between 60 and 100 min. GK treatments are between 3 and 5 times longer compared to RapidArc treatment techniques. CONCLUSION: Dosimetric parameters reflecting prescription dose conformality (CI), dose fall off (GI), radiation necrosis indicator (V 12Gy), and dose spread (Dspread) were compared between GK SRS and RapidArc SRS for multi-mets. RapidArc plans have smaller CI but larger GI. V 12Gy are comparable. GK appears better at reducing only very low-dose spread (<3 Gy). The treatment time of RapidArc SRS is significantly reduced compared to GK SRS. PMID- 26904502 TI - Effects of Charged Particles on Human Tumor Cells. AB - The use of charged particle therapy in cancer treatment is growing rapidly, in large part because the exquisite dose localization of charged particles allows for higher radiation doses to be given to tumor tissue while normal tissues are exposed to lower doses and decreased volumes of normal tissues are irradiated. In addition, charged particles heavier than protons have substantial potential clinical advantages because of their additional biological effects, including greater cell killing effectiveness, decreased radiation resistance of hypoxic cells in tumors, and reduced cell cycle dependence of radiation response. These biological advantages depend on many factors, such as endpoint, cell or tissue type, dose, dose rate or fractionation, charged particle type and energy, and oxygen concentration. This review summarizes the unique biological advantages of charged particle therapy and highlights recent research and areas of particular research needs, such as quantification of relative biological effectiveness (RBE) for various tumor types and radiation qualities, role of genetic background of tumor cells in determining response to charged particles, sensitivity of cancer stem-like cells to charged particles, role of charged particles in tumors with hypoxic fractions, and importance of fractionation, including use of hypofractionation, with charged particles. PMID- 26904506 TI - Efficient Rejoining of DNA Double-Strand Breaks despite Increased Cell-Killing Effectiveness following Spread-Out Bragg Peak Carbon-Ion Irradiation. AB - Radiotherapy of solid tumors with charged particles holds several advantages in comparison to photon therapy; among them conformal dose distribution in the tumor, improved sparing of tumor-surrounding healthy tissue, and an increased relative biological effectiveness (RBE) in the tumor target volume in the case of ions heavier than protons. A crucial factor of the biological effects is DNA damage, of which DNA double-strand breaks (DSBs) are the most deleterious. The reparability of these lesions determines the cell survival after irradiation and thus the RBE. Interestingly, using phosphorylated H2AX as a DSB marker, our data in human fibroblasts revealed that after therapy-relevant spread-out Bragg peak irradiation with carbon ions DSBs are very efficiently rejoined, despite an increased RBE for cell survival. This suggests that misrepair plays an important role in the increased RBE of heavy-ion radiation. Possible sources of erroneous repair will be discussed. PMID- 26904507 TI - A Delay from Diagnosis to Treatment Is Associated with a Decreased Overall Survival for Patients with Endometrial Cancer. AB - OBJECTIVES: While Caucasian women are more likely to be diagnosed with endometrial cancer compared to African-American women, the rate of mortality is higher for African Americans. The cause of this disparity is unknown. We analyzed the time interval from diagnosis of endometrial cancer to treatment as it pertains to race and socioeconomic factors and its possible impact on survival. METHODS: This was a retrospective, single institution chart review using a cancer registry database. We identified 889 patients who were diagnosed with endometrial cancer between January 2005 and June 2012. Clinicopathologic characteristics, demographics, insurance status, distance from medical center, body mass index (BMI), dates of diagnosis, and treatment were obtained from the medical records. Survival and association was determined by a one-way ANOVA test. RESULTS: At the time of the study, 699 patients were alive and 190 dead. The average age was noted to be 62 years (24-91 years). Stages I-IV disease accounted for 69, 6, 15, and 10%, respectively. White race accounted for 64%, African Americans 24%, and Hispanics 7% of our study population. Majority of patients were privately insured (n = 441) followed by Medicare (n = 375). The mean interval time from diagnosis to treatment was 47.5 days (0-363). A statistically significant difference was noted for this time interval with regard to both race and insurance status: white and African Americans (42.6 vs. 57.3 days, p = 0.048), privately insured and Medicare (38.4 vs. 54.1 days, p < 0.001). There was a significant association with increased risk of death with a longer delay (43.3 vs. 64.8 days, p < 0.001). No statistically significance was noted for distance from medical center or BMI. CONCLUSION: A significant increase in interval of time from diagnosis to treatment of endometrial cancer was seen in both race and insurance status. A longer interval from diagnosis to treatment was associated mortality. The causes of these delays are likely multifactorial but deem further investigation given these data. PMID- 26904505 TI - Ramadan Fasting and Patients with Cancer: State-of-the-Art and Future Prospects. AB - Ramadan fasting represents one of the five pillars of the Islam creed. Even though some subjects (among which patients) are exempted from observing this religious duty, they may be eager to share this particular moment of the year with their family and peers. However, there are no guidelines or standardized protocols that can help physicians to properly address the issue of patients with cancer fasting in Ramadan and correctly advising them. Moreover, in a more interconnected and globalized society, in which more and more Muslim patients live in the Western countries, this topic is of high interest also for the general practitioner. For this purpose, we carried out a systematic review on the subject. Our main findings are that (1) very few studies have been carried out, addressing this issue, (2) evidence concerning quality of life and compliance to treatment is contrasting and scarce, and (3) generally speaking, few patients ask their physicians whether they can safely fast or not. For these reasons, further research should be performed, given the relevance and importance of this topic. PMID- 26904509 TI - Vaccination of Elk (Cervus canadensis) with Brucella abortus Strain RB51 Overexpressing Superoxide Dismutase and Glycosyltransferase Genes Does Not Induce Adequate Protection against Experimental Brucella abortus Challenge. AB - In recent years, elk (Cervus canadensis) have been implicated as the source of Brucella abortus infection for numerous cattle herds in the Greater Yellowstone Area. In the face of environmental and ecological changes on the landscape, the range of infected elk is expanding. Consequently, the development of effective disease management strategies for wild elk herds is of utmost importance, not only for the prevention of reintroduction of brucellosis to cattle, but also for the overall health of the Greater Yellowstone Area elk populations. In two studies, we evaluated the efficacy of B. abortus strain RB51 over-expressing superoxide dismutase and glycosyltransferase for protecting elk from infection and disease caused by B. abortus after experimental infection with a virulent B. abortus strain. Our data indicate that the recombinant vaccine does not protect elk against brucellosis. Further, work is needed for development of an effective brucellosis vaccine for use in elk. PMID- 26904508 TI - Molecular Mechanisms and Potential Clinical Applications of Campylobacter jejuni Cytolethal Distending Toxin. AB - Cytolethal distending toxin (CDT), a genotoxin produced by Campylobacter jejuni, is composed of three subunits: CdtA, CdtB, and CdtC. CdtB is a DNase that causes DNA double-strand breaks (DSB) in the nucleus resulting in cell cycle arrest at the G2/M stage and apoptosis. CdtA and CdtC bind to cholesterol-rich microdomains on the cytoplasmic membrane, a process required for the delivery of CdtB to cells. Although a unique motif associated with cholesterol-binding activity has been identified in other pathogens, the mechanism underlying the interaction between the CdtA and CdtC subunits and membrane cholesterol remains unclear. Also, the processes of cell uptake and delivery of CdtB in host cells and the translocation of CdtB into the nucleus are only partially understood. In this review, we focus on the underlying relationship among CDT, membrane cholesterol, and the intracellular trafficking pathway as a unique mechanism for C. jejuni induced pathogenesis. Moreover, we discuss the clinical aspects of a possible therapeutic application of CDT in cancer therapy. Understanding the molecular mechanism of CDT-host interactions may provide insights into novel strategies to control C. jejuni infection and the development of potential clinical applications of CDT. PMID- 26904510 TI - The Two-Component System CpxRA Negatively Regulates the Locus of Enterocyte Effacement of Enterohemorrhagic Escherichia coli Involving sigma(32) and Lon protease. AB - Enterohemorrhagic Escherichia coli (EHEC) is a significant cause of serious human gastrointestinal disease worldwide. EHEC strains contain a pathogenicity island called the locus of enterocyte effacement (LEE), which encodes virulence factors responsible for damaging the gut mucosa. The Cpx envelope stress response of E. coli is controlled by a two-component system (TCS) consisting of a sensor histidine kinase (CpxA) and a cytoplasmic response regulator (CpxR). In this study, we investigated the role of CpxRA in the expression of LEE-encoded virulence factors of EHEC. We found that a mutation in cpxA significantly affected adherence of EHEC to human epithelial cells. Analysis of this mutant revealed the presence of high levels of CpxR which repressed transcription of grlA and ler, the main positive virulence regulators of the LEE, and influenced negatively the production of the type 3 secretion system-associated EspABD translocator proteins. It is known that CpxR activates rpoH (Sigma factor 32), which in turns activates transcription of the lon protease gene. We found that transcription levels of ler and grlA were significantly increased in the lon and cpxA lon mutants suggesting that lon is involved in down-regulating LEE genes. In addition, the Galleria mellonella model of infection was used to analyze the effect of the loss of the cpx and lon genes in EHEC's ability to kill the larvae. We found that the cpxA mutant was significantly deficient at killing the larvae however, the cpxA lon mutant which overexpresses LEE genes in vitro, was unable to kill the larvae, suggesting that virulence in the G. mellonella model is T3SS independent and that CpxA modulates virulence through a yet unknown EHEC-specific factor. Our data provides new insights and broadens our scope into the complex regulatory network of the LEE in which the CpxA sensor kinase plays an important role in a cascade involving both global and virulence regulators. PMID- 26904511 TI - The Many Faces of IpaB. AB - The type III secretion system (T3SS) is Shigella's most important virulence factor. The T3SS apparatus (T3SA) is comprised of an envelope-spanning basal body and an external needle topped by a tip complex protein called IpaD. This nanomachine is used to deliver effector proteins into host cells to promote pathogen entry. A key component of the matured T3SS needle tip complex is the translocator protein IpaB. IpaB can exist in multiple states when prepared as a recombinant protein, however, it has also been described as having additional roles in Shigella pathogenesis. This mini-review will briefly describe some of the features of IpaB as a T3SS needle tip protein, as a pore-forming translocator protein and as an effector protein. Reflection on the potential importance of the different in vitro states of IpaB on its function and importance in serotype independent vaccines is also provided. PMID- 26904512 TI - H-NS Nucleoid Protein Controls Virulence Features of Klebsiella pneumoniae by Regulating the Expression of Type 3 Pili and the Capsule Polysaccharide. AB - Klebsiella pneumoniae is an opportunistic pathogen causing nosocomial infections. Main virulence determinants of K. pneumoniae are pili, capsular polysaccharide, lipopolysaccharide, and siderophores. The histone-like nucleoid-structuring protein (H-NS) is a pleiotropic regulator found in several gram-negative pathogens. It has functions both as an architectural component of the nucleoid and as a global regulator of gene expression. We generated a Deltahns mutant and evaluated the role of the H-NS nucleoid protein on the virulence features of K. pneumoniae. A Deltahns mutant down-regulated the mrkA pilin gene and biofilm formation was affected. In contrast, capsule expression was derepressed in the absence of H-NS conferring a hypermucoviscous phenotype. Moreover, H-NS deficiency affected the K. pneumoniae adherence to epithelial cells such as A549 and HeLa cells. In infection experiments using RAW264.7 and THP-1 differentiated macrophages, the Deltahns mutant was less phagocytized than the wild-type strain. This phenotype was likely due to the low adherence to these phagocytic cells. Taken together, our data indicate that H-NS nucleoid protein is a crucial regulator of both T3P and CPS of K. pneumoniae. PMID- 26904514 TI - How Shigella Utilizes Ca(2+) Jagged Edge Signals during Invasion of Epithelial Cells. AB - Shigella, the causative agent of bacillary dysentery invades intestinal epithelial cells using a type III secretion system (T3SS). Through the injection of type III effectors, Shigella manipulates the actin cytoskeleton to induce its internalization in epithelial cells. At early invasion stages, Shigella induces atypical Ca(2+) responses confined at entry sites allowing local cytoskeletal remodeling for bacteria engulfment. Global Ca(2+) increase in the cell triggers the opening of connexin hemichannels at the plasma membrane that releases ATP in the extracellular milieu, favoring Shigella invasion and spreading through purinergic receptor signaling. During intracellular replication, Shigella regulates inflammatory and death pathways to disseminate within the epithelium. At later stages of infection, Shigella downregulates hemichannel opening and the release of extracellular ATP to dampen inflammatory signals. To avoid premature cell death, Shigella activates cell survival by upregulating the PI3K/Akt pathway and downregulating the levels of p53. Furthermore, Shigella interferes with pro apoptotic caspases, and orients infected cells toward a slow necrotic cell death linked to mitochondrial Ca(2+) overload. In this review, we will focus on the role of Ca(2+) responses and their regulation by Shigella during the different stages of bacterial infection. PMID- 26904515 TI - Interactions between Shigella flexneri and the Autophagy Machinery. AB - Autophagy, an intracellular degradation process, is increasingly recognized as having important roles in host defense. Interactions between Shigella flexneri and the autophagy machinery were first discovered in 2005. Since then, work has shown that multiple autophagy pathways are triggered by S. flexneri, and autophagic responses can have different roles during Shigella infection. Here, we review the interactions between S. flexneri and the autophagy machinery, highlighting that studies using Shigella can reveal the breadth of autophagic responses available to the host. PMID- 26904516 TI - Shigella Iron Acquisition Systems and their Regulation. AB - Survival of Shigella within the host is strictly dependent on the ability of the pathogen to acquire essential nutrients, such as iron. As an innate immune defense against invading pathogens, the level of bio-available iron within the human host is maintained at exceeding low levels, by sequestration of the element within heme and other host iron-binding compounds. In response to sequestration mediated iron limitation, Shigella produce multiple iron-uptake systems that each function to facilitate the utilization of a specific host-associated source of nutrient iron. As a mechanism to balance the essential need for iron and the toxicity of the element when in excess, the production of bacterial iron acquisition systems is tightly regulated by a variety of molecular mechanisms. This review summarizes the current state of knowledge on the iron-uptake systems produced by Shigella species, their distribution within the genus, and the molecular mechanisms that regulate their production. PMID- 26904520 TI - Patient flows: runners, specials and strangers. PMID- 26904513 TI - The Basics of Bacteriuria: Strategies of Microbes for Persistence in Urine. AB - Bacteriuria, the presence of bacteria in urine, is associated with asymptomatic, as well as symptomatic, urinary tract infection (UTI). Bacteriuria underpins some of the dynamics of microbial colonization of the urinary tract, and probably impacts the progression and persistence of infection in some individuals. Recent molecular discoveries in vitro have elucidated how some key bacterial traits can enable organisms to survive and grow in human urine as a means of microbial fitness adaptation for UTI. Several microbial characteristics that confer bacteruric potential have been identified including de novo synthesis of guanine, relative resistance to D-serine, and catabolism of malic acid. Microbial characteristics such as these are increasingly being defined through the use of synthetic human urine (SHU) in vitro as a model to mimic the in vivo environment that bacteria encounter in the bladder. There is considerable variation in the SHU model systems that have been used to study bacteriuria to date, and this influences the utility of these models. In this review, we discuss recent advances in our understanding of bacteruric potential with a focus on the specific mechanisms underlying traits that promote the growth of bacteria in urine. We also review the application of SHU in research studies modeling UTI and discuss the chemical makeup, and benefits and limitations that are encountered in utilizing SHU to study bacterial growth in urine in vitro. PMID- 26904517 TI - Brucella suis Vaccine Strain 2 Induces Endoplasmic Reticulum Stress that Affects Intracellular Replication in Goat Trophoblast Cells In vitro. AB - Brucella has been reported to impair placental trophoblasts, a cellular target where Brucella efficiently replicates in association with the endoplasmic reticulum (ER), and ultimately trigger abortion in pregnant animals. However, the precise effects of Brucella on trophoblast cells remain unclear. Here, we describe the infection and replication of Brucella suis vaccine strain 2 (B.suis.S2) in goat trophoblast cells (GTCs) and the cellular and molecular responses induced in vitro. Our studies demonstrated that B.suis.S2 was able to infect and proliferate to high titers, hamper the proliferation of GTCs and induce apoptosis due to ER stress. Tunicamycin (Tm), a pharmacological chaperone that strongly mounts ER stress-induced apoptosis, inhibited B.suis.S2 replication in GTCs. In addition, 4 phenyl butyric acid (4-PBA), a pharmacological chaperone that alleviates ER stress-induced apoptosis, significantly enhanced B.suis.S2 replication in GTCs. The Unfolded Protein Response (UPR) chaperone molecule GRP78 also promoted B.suis.S2 proliferation in GTCs by inhibiting ER stress-induced apoptosis. We also discovered that the IRE1 pathway, but not the PERK or ATF6 pathway, was activated in the process. However, decreasing the expression of phosphoIRE1alpha and IRE1alpha proteins with Irestatin 9389 (IRE1 antagonist) in GTCs did not affect the proliferation of B.suis.S2. Although GTC implantation was not affected upon B.suis.S2 infection, progesterone secretion was suppressed, and prolactin and estrogen secretion increased; these effects were accompanied by changes in the expression of genes encoding key steroidogenic enzymes. This study systematically explored the mechanisms of abortion in Brucella infection from the viewpoint of pathogen invasion, ER stress and reproductive endocrinology. Our findings may provide new insight for understanding the mechanisms involved in goat abortions caused by Brucella infection. PMID- 26904518 TI - Tissue-Specific Signatures in the Transcriptional Response to Anaplasma phagocytophilum Infection of Ixodes scapularis and Ixodes ricinus Tick Cell Lines. AB - Anaplasma phagocytophilum are transmitted by Ixodes spp. ticks and have become one of the most common and relevant tick-borne pathogens due to their impact on human and animal health. Recent results have increased our understanding of the molecular interactions between Ixodes scapularis and A. phagocytophilum through the demonstration of tissue-specific molecular pathways that ensure pathogen infection, development and transmission by ticks. However, little is known about the Ixodes ricinus genes and proteins involved in the response to A. phagocytophilum infection. The tick species I. scapularis and I. ricinus are evolutionarily closely related and therefore similar responses are expected in A. phagocytophilum-infected cells. However, differences may exist between I. scapularis ISE6 and I. ricinus IRE/CTVM20 tick cells associated with tissue specific signatures of these cell lines. To address this hypothesis, the transcriptional response to A. phagocytophilum infection was characterized by RNA sequencing and compared between I. scapularis ISE6 and I. ricinus IRE/CTVM20 tick cell lines. The transcriptional response to infection of I. scapularis ISE6 cells resembled that of tick hemocytes while the response in I. ricinus IRE/CTVM20 cells was more closely related to that reported previously in infected tick midguts. The inhibition of cell apoptosis by A. phagocytophilum appears to be a key adaptation mechanism to facilitate infection of both vertebrate and tick cells and was used to investigate further the tissue-specific response of tick cell lines to pathogen infection. The results supported a role for the intrinsic pathway in the inhibition of cell apoptosis by A. phagocytophilum infection of I. scapularis ISE6 cells. In contrast, the results in I. ricinus IRE/CTVM20 cells were similar to those obtained in tick midguts and suggested a role for the JAK/STAT pathway in the inhibition of apoptosis in tick cells infected with A. phagocytophilum. Nevertheless, tick cell lines were derived from embryonated eggs and may contain various cell populations with different morphology and behavior that could affect transcriptional response to infection. These results suggested tissue-specific signatures in I. scapularis ISE6 and I. ricinus IRE/CTVM20 tick cell line response to A. phagocytophilum infection that support their use as models for the study of tick-pathogen interactions. PMID- 26904521 TI - Calcifying tendinitis of the shoulder: arthroscopic needling versus complete calcium removal and rotator cuff repair. A prospective comparative study. AB - PURPOSE: the aim of the present study was to verify the differences in the clinical outcomes of two arthroscopic techniques used to treat calcifying tendinitis of the shoulder: needling versus complete removal of the calcium deposit and tendon repair. METHODS: from September 2010 to September 2012, 40 patients with calcifying tendinitis of the rotator cuff were arthroscopically treated by the same surgeon using one of the two following techniques: needling (Group 1) and complete removal of the calcium deposit and tendon repair with suture anchors (Group 2). Both groups followed the same rehabilitation program. The two groups were compared at 6 and 12 months of follow-up for the presence of residual calcifications and for the following clinical outcomes: Constant score, American Shoulder and Elbow Surgeons Evaluation Form (ASES) shoulder score, University of California Los Angeles (UCLA) shoulder rating scale, Simple Shoulder Test (SST) and Visual Analogue Scale (VAS). RESULTS: all the clinical scores (Constant, ASES, UCLA, SST and VAS scores) improved significantly between baseline and postoperative follow-up, both at 6 and at 12 months. No differences at final follow-up were found between the two groups. CONCLUSIONS: both the techniques were effective in solving the symptoms of calcifying tendinitis of the shoulder. Clinical scores improved in both groups. Residual calcifications were found in only a few cases and were always less than 10 mm. LEVEL OF EVIDENCE: Level II, prospective comparative study. PMID- 26904523 TI - Anterior cruciate ligament reconstruction and rehabilitation: predictors of functional outcome. AB - Surgical reconstruction of an injured anterior cruciate ligament (ACL) leads to full recovery of function and sports activity in a high percentage of cases. The aim of the present study was to analyze variables related to the patient, the surgical technique and the post-surgical rehabilitation methods, seeking to identify predictors of outcome and recovery time after ACL reconstruction. One hundred and four patients (81 M, 23 F) undergoing a step-based rehabilitation protocol after ACL reconstruction were evaluated. 43.2% of them had an isolated ACL lesion, whereas 56.8% had one or more concurrent injuries. Data relating to personal characteristics, surgery and post-operative management were collected and analyzed for correlation. Clinical outcome was evaluated with IKDC subjective score and the Tegner score, and the time to reach full recovery was noted as well. Young patients with a higher pre-injury Tegner activity level or who practice sport at professional level, no concurrent capsular lesions and no postoperative knee bracing had better clinical results and took shorter time to recover. Also, a higher percentage of on-the-field rehabilitation sessions, and absence of significant muscle strength deficits at the first knee isokinetic test emerged as rehabilitation-related factors leading to a better post-surgical outcome. Personal, surgical and rehabilitation factors should be considered in order to optimize patient management and maximize the expected results. Further studies are needed to find the strongest factors in different patients. LEVEL OF EVIDENCE: Level IV, retrospective study. PMID- 26904522 TI - Treatment of unstable osteochondritis dissecans in adults with autogenous osteochondral grafts (Mosaicplasty): long-term results. AB - PURPOSE: the unstable osteochondritis dissecans (OCD-type II and III according to the ICRS classification) of the knee largher than > 2.5 cm(2) in adults are uncommon lesions and there is no consensus on how to treat them. Medium-term studies have reported good results using autogenous osteochondral plugs (mosaicplasty). The aim of this study is to analyze the long-term results of this technique for the treatment of unstable OCD in a selected group of adult patients. METHODS: four patients with OCD at either one of the femoral condyles were included in this prospective study. The average age was 21.2 years (range, 18-24 years). The OCD lesions were classified as type II in three patients and type III in one patient and the average size was 3.8 cm(2) (range, 2.55-5.1 cm(2)). The lesions were treated in situ with a variable number of autogenous osteochondral plugs (O 4.5 mm(2)). The Modified Cincinnati, Lysholm II and Tegner scores were used for clinical and functional evaluation. Magnetic resonance arthrography (MRA) was performed before surgery and at 2, 5 and 10 years after surgery. A modified MOCART score was used to evaluate MRA findings. RESULTS: the average follow-up duration was ten years and 6 months (range, 10-11 years). No complications occurred. At the final follow-up, all scores (clinical, functional and MOCART) improved. In all but one of the patients MRA showed complete osteochondral repair. CONCLUSIONS: the fixation of large and unstable OCD lesions with mosaicplasty may be a good option for treating type II or III OCD lesions in adults. The advantages of this technique include stable fixation, promotion of blood supply to the base of the OCD fragment, and grafting of autologous cancellous bone that stimulates healing with preservation of the articular surface. LEVEL OF EVIDENCE: Level IV, therapeutic case series. PMID- 26904524 TI - Assessing hospital cost of joint arthroplasty. AB - PURPOSE: total joint replacement is one of the most successful procedures in medicine and cost reimbursements to hospitals for the joint arthroplasty diagnosis-related group are among the largest payments made by a Regional Health Service. Despite the popularity of these procedures, there are few high-quality cost-effectiveness studies on this topic. This study evaluates the cost of total joint arthroplasty performed in a district hospital. METHODS: direct and indirect costs have been measured and patient procedure pathway was analyzed subdivided into three stages: surgical procedure, inpatient care and outpatient clinic. RESULTS: the cost of the surgical procedure stage was calculated as 3,798 euros, while that of the inpatient stage was 2,924 euros. The mean hospital costs per procedure amounted to 6,952 euros. CONCLUSIONS: although the Health Service tariffs fully reimburse the cost of providing a joint replacement, our data contribute to point out the role of hospital staff's organization to support sustainable improvements on health care for joint replacement surgery. LEVEL OF EVIDENCE: Level VI, single economic evaluation. PMID- 26904525 TI - The emotional coaching model: quantitative and qualitative research into relationships, communication and decisions in physical and sports rehabilitation. AB - The emotional coaching model uses quantitative and qualitative elements to demonstrate some assumptions relevant to new methods of treatment in physical rehabilitation, considering emotional, cognitive and behavioral aspects in patients, whether or not they are sportsmen. Through quantitative tools (Tampa Kinesiophobia Scale, Emotional Interview Test, Previous Re-Injury Test, and reports on test scores) and qualitative tools (training contracts and relationships of emotional alliance or "contagion"), we investigate initial assumptions regarding: the presence of a cognitive and emotional mental state of impasse in patients at the beginning of the rehabilitation pathway; the curative value of the emotional alliance or "emotional contagion" relationship between healthcare provider and patient; the link between the patient's pathology and type of contact with his own body and emotions; analysis of the psychosocial variables for the prediction of possible cases of re-injury for patients who have undergone or are afraid to undergo reconstruction of the anterior cruciate ligament (ACL). Although this approach is still in the experimental stage, the scores of the administered tests show the possibility of integrating quantitative and qualitative tools to investigate and develop a patient's physical, mental and emotional resources during the course of his rehabilitation. Furthermore, it seems possible to identify many elements characterizing patients likely to undergo episodes of re-injury or to withdraw totally from sporting activity. In particular, such patients are competitive athletes, who fear or have previously undergone ACL reconstruction. The theories referred to (the transactional analysis theory, self-determination theory) and the tools used demonstrate the usefulness of continuing this research in order to build a shared coaching model treatment aimed at all patients, sportspeople or otherwise, which is not only physical but also emotional, cognitive and behavioral. PMID- 26904526 TI - Osteochondral repair in hemophilic ankle arthropathy: from current options to future perspectives. AB - Young hemophilic patients are frequently affected by ankle arthropathy. At the end stage of the disease, the current treatments are arthrodesis and arthroplasty, which have significant drawbacks. Validated procedures capable of slowing down or even arresting the progression towards the end stage are currently lacking. This review aims to discuss the rationale for and feasibility of applying, in mild hemophilic ankle arthropathy, the main techniques currently used to treat osteochondral defects, focusing in particular on ankle distraction, chondrocyte implantation, mesenchymal stem cell transplantation, allograft transplantation and the use of growth factors. To date, ankle distraction is the only procedure that has been successfully used in hemophilic ankle arthropathy. The use of mesenchymal stem cells have recently been evaluated as feasible for osteochondral repair in hemophilic patients. There may be a rationale for the use of growth factors if they are combined with the previous techniques, which could be useful to arrest the progression of the degeneration or delay end-stage procedures. PMID- 26904528 TI - Medial collateral ligament reconstruction during TKA: a new approach and surgical technique. AB - Medial collateral ligament (MCL) injuries during total knee arthroplasty are rare but severe complications. They can be treated conservatively, by increasing prosthetic constraint, by using a thicker polyethylene insert, or by directly suturing the ligament. A prosthesis is successful to the extent that it ensures long-term knee stability. We describe our surgical approach to the restoration of knee joint stability in MCL deficiency: a reconstructive technique using the semitendinosus tendon. PMID- 26904527 TI - Reducing periprosthetic joint infection: what really counts? AB - Periprosthetic joint infection (PJI) remains one of the most challenging complications after joint arthroplasty. Despite improvements in surgical techniques and in the use of antibiotic prophylaxis, it remains a major cause of implant failure and need for revision. PJI is associated with both human host related and bacterial agent-related factors that can interact in all the phases of the procedure (preoperative, intraoperative and postoperative). Prevention is the first strategy to implement in order to minimize this catastrophic complication. The present review focuses on the preoperative period, and on what to do once risk factors are fully understood and have been identified. PMID- 26904529 TI - Traumatic bilateral Achilles tendon rupture in a young athlete treated with percutaneous tenorrhaphy. AB - While rupture of the Achilles tendon is one of the most frequent injuries sustained in sports and physical activity, bilateral Achilles tendon rupture is uncommon. We present the case of a 33-year-old man who sustained a bilateral Achilles tendon rupture in the absence of predisposing factors. The lesions were managed by percutaneous tenorrhaphy and casting. Six months after surgery he was able to return to his daily-life activities and to perform light sports activity. The Authors review the current literature on the management of this rare condition in young people, with or without risk factors. PMID- 26904530 TI - Association of a hi-tech with a bio-tech technique in the treatment of early osteoarthritis of the knee: a case report. AB - Meniscal replacement to treat early osteoarthritis of the knee after meniscectomy may be accompanied by other surgical procedures to treat factors predisposing to a negative intervention outcome. Overload of the medial compartment in slight varus can be reduced by applying the new KineSpring system, which can promote the best possible outcome of a biodegradable meniscal scaffold implantation, without producing biomechanical and anatomical alterations of the joint. This is the first case report on the combination of these hi-tech and bio-tech techniques. PMID- 26904531 TI - Work-Life Balance? It Is Not about Balance, but Priorities. PMID- 26904532 TI - Transdisciplinary Project Communication and Knowledge Sharing Experiences in Tanzania and Zambia through a One Health Lens. AB - The project "Strengthening food and nutrition security through family poultry and crop integration in Tanzania and Zambia" brings together animal, crop, and human health specialists, economists, ecologists, social scientists, and practitioners to work with participating communities. It aims to increase poultry value chain, crop farming systems efficiency, and household food and nutrition security and thus requires understanding of, and ability to work effectively within, complex systems. In this context, communication knowledge sharing and synthesis between stakeholders from diverse backgrounds and a range of experiences, perspectives, agendas, and knowledge is a challenge. To address this situation, communication is conceived as a dialog and a participatory process bringing together all stakeholders. This process results in unanticipated and unexpected results that require a high degree of flexibility and adaptability from team members. The paper analyses the approach and aim of the communication strategy developed for the project and the challenges faced. PMID- 26904533 TI - Issues to Consider Before Initiating a Project in Medical Geography. PMID- 26904534 TI - Newborn Health Interventions and Challenges for Implementation in Nepal. AB - Neonatal mortality is a major challenge in reducing child mortality rates in Nepal. Despite efforts by the Government of Nepal, data from the last three demographic and health surveys show a rise in the contribution of neonatal deaths to infant and child mortality. The Government of Nepal has implemented community based programs that were piloted and then scaled up based on lessons learned. These programs include, but are not limited to ensuring safe motherhood, birth preparedness package, community-based newborn care package, and integrated management of childhood illnesses. Despite the implementation of such programs on a larger scale, their effective coverage is yet to be achieved. Health system challenges included an inadequate policy environment, funding gaps, inadequate procurement, and insufficient supplies of commodities, while human resource management has been found to be impeding service delivery. Such bottlenecks at policy, institutional and service delivery level need to be addressed incorporating health information in decision-making as well as working in partnership with communities to facilitate the utilization of available services. PMID- 26904535 TI - The Influence of Neurocognitive Impairment on HIV Risk Behaviors and Intervention Outcomes among High-Risk Substance Users: A Systematic Review. AB - Neurocognitive impairment (NCI) among high-risk substance users poses a substantial barrier to reducing risk behaviors in this population. Previous work suggests that NCI is intertwined in a close, reciprocal relationship with risk behaviors. Not only does substance use worsen cognitive impairment but cognitive impairment may also reduce the efficacy of interventions aimed at reducing risk and improving medication adherence. In this systematic review, we examine the potential impact of substance abuse and cognitive functioning in the context of HIV risk behaviors and risk-reduction intervention outcomes. The findings thus far suggest that, in order to be effective, risk-reduction interventions must take into account the impact of NCI on learning, memory, and behavior. PMID- 26904536 TI - Are Extracted Materials Truly Representative of Original Samples? Impact of C18 Extraction on CDOM Optical and Chemical Properties. AB - Some properties of dissolved organic matter (DOM) and chromophoric dissolved organic matter (CDOM) can be easily measured directly on whole waters, while others require sample concentration and removal of natural salts. To increase CDOM content and eliminate salts, solid phase extraction (SPE) is often employed. Biases following extraction and elution are inevitable, thus raising the question of how truly representative the extracted material is of the original. In this context, we investigated the wavelength dependence of extraction efficiency for C18 cartridges with respect to CDOM optical properties using samples obtained from the Middle Atlantic Bight (MAB) and the Equatorial Atlantic Ocean (EAO). Further, we compared the optical changes of C18 extracts and the corresponding whole water following chemical reduction with sodium borohydride (NaBH4). C18 cartridges preferentially extracted long-wavelength absorbing/emitting material for samples impacted by riverine input. Extraction efficiency overall decreased with offshore distance away from riverine input. Spectral slopes of C18-OM samples were also almost always lower than those of their corresponding CDOM samples supporting the preferential extraction of higher molecular weight absorbing material. The wavelength dependence of the optical properties (absorption, fluorescence emission, and quantum yield) of the original water samples and their corresponding extracted material were very similar. C18 extracts and corresponding water samples further exhibited comparable optical changes following NaBH4 reduction, thus suggesting a similarity in nature (structure) of the optically active extracted material, independent of geographical locale. Altogether, these data suggested a strong similarity between C18 extracts and corresponding whole waters, thus indicating that extracts are representative of the CDOM content of original waters. PMID- 26904538 TI - A First Attempt into the Production of Acylglycerol Mixtures from Echium Oil. AB - Enzymatic glycerolysis of Echium oil (Echium plantagineum) has been carried out in the presence of four commercial lipases. Different pretreatments of the reaction mixture, such as high pressure homogenization and addition of food grade monoolein as an emulsifier, were evaluated to test their influence on the glycerolysis reaction. In addition, the impact of reducing temperature and the utilization of a solvent generally recognized as safe as a flavoring agent, such as limonene, were also investigated. Conversion of ca. 60-70% of triacylglycerols and production of ca. 25-30% of monoacylglycerols (MAGs) were attained. Finally, at the best reaction conditions, the glycerolysis reaction was scaled up at pilot plant and the product mixture obtained was fractionated via molecular distillation. From this stage, two products were attained: a distillate containing 80% of MAGs and a residue containing approximately 50% of diacylglycerols and 50% of triacylglycerols. All these mixtures can be utilized as self-emulsifying vehicles for the formulation of bioactive substances and also as precursors for the production of structured bioactive lipids. PMID- 26904537 TI - The Reverse Transcriptase Encoded by LINE-1 Retrotransposons in the Genesis, Progression, and Therapy of Cancer. AB - In higher eukaryotic genomes, Long Interspersed Nuclear Element 1 (LINE-1) retrotransposons represent a large family of repeated genomic elements. They transpose using a reverse transcriptase (RT), which they encode as part of the ORF2p product. RT inhibition in cancer cells, either via RNA interference dependent silencing of active LINE-1 elements, or using RT inhibitory drugs, reduces cancer cell proliferation, promotes their differentiation and antagonizes tumor progression in animal models. Indeed, the non-nucleoside RT inhibitor efavirenz has recently been tested in a phase II clinical trial with metastatic prostate cancer patients. An in-depth analysis of ORF2p in a mouse model of breast cancer showed ORF2p to be precociously expressed in precancerous lesions and highly abundant in advanced cancer stages, while being barely detectable in normal breast tissue, providing a rationale for the finding that RT-expressing tumors are therapeutically sensitive to RT inhibitors. We summarize mechanistic and gene profiling studies indicating that abundant LINE-1-derived RT can "sequester" RNA substrates for reverse transcription in tumor cells, entailing the formation of RNA:DNA hybrid molecules and impairing the overall production of regulatory miRNAs, with a global impact on the cell transcriptome. Based on these data, LINE-1-ORF2 encoded RT has a tumor-promoting potential that is exerted at an epigenetic level. We propose a model whereby LINE1-RT drives a previously unrecognized global regulatory process, the deregulation of which drives cell transformation and tumorigenesis with possible implications for cancer cell heterogeneity. PMID- 26904539 TI - Solvent-Free Lipase-Catalyzed Synthesis of Diacylgycerols as Low-Calorie Food Ingredients. AB - Problems derived from obesity and overweight have recently promoted the development of fat substitutes and other low-calorie foods. On the one hand, fats with short- and medium-chain fatty acids are a source of quick energy, easily hydrolyzable and hardly stored as fat. Furthermore, 1,3-diacylglycerols are not hydrolyzed to 2-monoacylglycerols in the gastrointestinal tract, reducing the formation of chylomicron and lowers the serum level of triacylglycerols by decreasing its resynthesis in the enterocyte. In this work, these two effects were combined to synthesize short- and medium-chain 1,3-diacylglycerols, leading to a product with great potential as for their low-calorie properties. Lipase catalyzed transesterification reactions were performed between short- and medium chain fatty acid ethyl esters and glycerol. Different variables were investigated, such as the type of biocatalyst, the molar ratio FAEE:glycerol, the adsorption of glycerol on silica gel, or the addition of lecithin. Best reaction conditions were evaluated considering the percentage of 1,3-DAG produced and the reaction rate. Except Novozym 435 (Candida antarctica), other lipases required the adsorption of glycerol on silica gel to form acylglycerols. Lipases that gave the best results with adsorption were Novozym 435 and Lipozyme RM IM (Rhizomucor miehei) with 52 and 60.7% DAG at 32 h, respectively. Because of its specificity for sn-1 and sn-3 positions, lipases leading to a higher proportion of 1,3-DAG vs. 1,2-DAG were Lipozyme RM IM (39.8 and 20.9%, respectively) and Lipase PLG (Alcaligenes sp.) (35.9 and 19.3%, respectively). By adding 1% (w/w) of lecithin to the reaction with Novozym 435 and raw glycerol, the reaction rate was considerably increased from 41.7 to 52.8% DAG at 24 h. PMID- 26904540 TI - Systems Perturbation Analysis of a Large-Scale Signal Transduction Model Reveals Potentially Influential Candidates for Cancer Therapeutics. AB - Dysregulation in signal transduction pathways can lead to a variety of complex disorders, including cancer. Computational approaches such as network analysis are important tools to understand system dynamics as well as to identify critical components that could be further explored as therapeutic targets. Here, we performed perturbation analysis of a large-scale signal transduction model in extracellular environments that stimulate cell death, growth, motility, and quiescence. Each of the model's components was perturbed under both loss-of function and gain-of-function mutations. Using 1,300 simulations under both types of perturbations across various extracellular conditions, we identified the most and least influential components based on the magnitude of their influence on the rest of the system. Based on the premise that the most influential components might serve as better drug targets, we characterized them for biological functions, housekeeping genes, essential genes, and druggable proteins. The most influential components under all environmental conditions were enriched with several biological processes. The inositol pathway was found as most influential under inactivating perturbations, whereas the kinase and small lung cancer pathways were identified as the most influential under activating perturbations. The most influential components were enriched with essential genes and druggable proteins. Moreover, known cancer drug targets were also classified in influential components based on the affected components in the network. Additionally, the systemic perturbation analysis of the model revealed a network motif of most influential components which affect each other. Furthermore, our analysis predicted novel combinations of cancer drug targets with various effects on other most influential components. We found that the combinatorial perturbation consisting of PI3K inactivation and overactivation of IP3R1 can lead to increased activity levels of apoptosis-related components and tumor-suppressor genes, suggesting that this combinatorial perturbation may lead to a better target for decreasing cell proliferation and inducing apoptosis. Finally, our approach shows a potential to identify and prioritize therapeutic targets through systemic perturbation analysis of large-scale computational models of signal transduction. Although some components of the presented computational results have been validated against independent gene expression data sets, more laboratory experiments are warranted to more comprehensively validate the presented results. PMID- 26904542 TI - Potentiating the Activity of Nisin against Escherichia coli. AB - Lantibiotics are antimicrobial (methyl)lanthionine-containing peptides produced by various Gram-positive bacteria. The model lantibiotic, nisin, binds lipid II in the cell membrane. Additionally, after binding it can insert into the membrane creating a pore. Nisin can efficiently inhibit the growth of Gram-positive bacteria and resistance is rarely observed. However, the activity of lantibiotics is at least 100-fold lower against certain Gram-negative bacteria. This is caused by the fact that Gram-negative bacteria have an outer membrane that hinders the peptides to reach lipid II, which is located in the inner membrane. Improving the activity of lantibiotics against Gram-negative bacteria could be achieved if the outer membrane traversing efficiency is increased. Here, several anti-Gram negative peptides (e.g., apidaecin 1b, oncocin), or parts thereof, were fused to the C-terminus of either a truncated version of nisin containing the first three/five rings or full length nisin. The activities of these fusion peptides were tested against Gram-negative pathogens. Our results showed that when an eight amino acids (PRPPHPRL) tail from apidaecin 1b was attached to nisin, the activity of nisin against Escherichia coli CECT101 was increased more than two times. This research presents a new and promising method to increase the anti Gram-negative activity of lantibiotics. PMID- 26904541 TI - In Vitro Tumor Models: Advantages, Disadvantages, Variables, and Selecting the Right Platform. AB - In vitro tumor models have provided important tools for cancer research and serve as low-cost screening platforms for drug therapies; however, cancer recurrence remains largely unchecked due to metastasis, which is the cause of the majority of cancer-related deaths. The need for an improved understanding of the progression and treatment of cancer has pushed for increased accuracy and physiological relevance of in vitro tumor models. As a result, in vitro tumor models have concurrently increased in complexity and their output parameters further diversified, since these models have progressed beyond simple proliferation, invasion, and cytotoxicity screens and have begun recapitulating critical steps in the metastatic cascade, such as intravasation, extravasation, angiogenesis, matrix remodeling, and tumor cell dormancy. Advances in tumor cell biology, 3D cell culture, tissue engineering, biomaterials, microfabrication, and microfluidics have enabled rapid development of new in vitro tumor models that often incorporate multiple cell types, extracellular matrix materials, and spatial and temporal introduction of soluble factors. Other innovations include the incorporation of perfusable microvessels to simulate the tumor vasculature and model intravasation and extravasation. The drive toward precision medicine has increased interest in adapting in vitro tumor models for patient-specific therapies, clinical management, and assessment of metastatic potential. Here, we review the wide range of current in vitro tumor models and summarize their advantages, disadvantages, and suitability in modeling specific aspects of the metastatic cascade and drug treatment. PMID- 26904544 TI - Video Capsule Endoscopy: A Tool for the Assessment of Small Bowel Transit Time. AB - PURPOSE: Video capsule endoscopy (VCE) is a procedure that uses a wireless camera to take pictures of the gastrointestinal (GI) tract. A wireless motility capsule (WMC) of a similar size has been developed, which measures pH, pressure, and temperature and can be used to assess regional and total GI transit times. VCE could also potentially be used as a tool for measuring small bowel transit time (SBTT). METHODS: This study was designed to obtain SBTT from VCE and compare it with historical data generated by WMC. Gastric transit time (GTT) was also measured. Patients were included if the indication for VCE was either iron deficiency anemia (IDA) or overt obscure GI bleed (OOGIB), and they did not have any known motility disorder. Results from VCE were also compared in diabetic vs. non-diabetic patients. RESULTS: There were a total of 147 VCE studies performed, including 42 for OOGIB and 105 for IDA. Median GTT and SBTT were 0.3 and 3.6 h, respectively. The overall median GTT and SBTT were 0.3 and 3.6 h, respectively, in the IDA group compared with 0.3 and 3.4 h in the OOGIB group. When compared with WMC, the GTT and SBTT were significantly faster in both groups (GTT: 3.6 h and SBTT: 4.6 h). The median GTT and SBTT were not significantly different in diabetics vs. non-diabetics [GTT: 17.5 vs. 18.0 min (P = 0.86) and SBTT: 3.9 h (237 min) vs. 3.8 h (230 min), respectively (P = 0.90)]. CONCLUSION: SBTT as measured using VCE is not significantly different in OOGIB compared with IDA. Both GTT and SBTT are significantly faster as assessed by VCE, which is initiated in the fasting state, compared with WMC measurement, which is initiated after a standard meal. In summary, VCE could potentially be used for measuring SBTT in the fasting state. PMID- 26904543 TI - Planarian Body-Wall Muscle: Regeneration and Function beyond a Simple Skeletal Support. AB - The body-wall musculature of adult planarians consists of intricately organized muscle fibers, which after amputation are regenerated rapidly and with great precision through the proliferation and differentiation of pluripotent stem cells. These traits make the planarian body-wall musculature a potentially useful model for the study of cell proliferation, differentiation, and pattern formation. Planarian body-wall muscle shows some ambiguous features common to both skeletal and smooth muscle cells. However, its skeletal nature is implied by the expression of skeletal myosin heavy-chain genes and the myogenic transcription factor myoD. Where and when planarian stem cells become committed to the myogenic lineage during regeneration, how the new muscle cells are integrated into the pre-existing muscle net, and the identity of the molecular pathway controlling the myogenic gene program are key aspects of planarian muscle regeneration that need to be addressed. Expression of the conserved transcription factor myoD has been recently demonstrated in putative myogenic progenitors. Moreover, recent studies suggest that differentiated muscle cells may provide positional information to planarian stem cells during regeneration. Here, I review the limited available knowledge on planarian muscle regeneration. PMID- 26904545 TI - Elevated Serum Levels of Alpha-Fetoprotein in Patients with Infantile Hemangioma Are Not Derived from within the Tumor. AB - AIMS: The embryonic-like stem cell origin of infantile hemangioma (IH) and the observed elevated serum levels of alpha-fetoprotein (AFP) in patients with hepatic IH led us to investigate if this tumor was the source of AFP. MATERIALS AND METHODS: We measured serial serum levels of AFP in patients with problematic proliferating IH treated with surgical excision or propranolol treatment. We also investigated the expression of AFP in extrahepatic IH samples using immunohistochemical staining, mass spectrometry, NanoString gene expression analysis, and in situ hybridization. RESULTS: Serum levels of AFP normalized following surgical excision or propranolol treatment. Multiple regression analysis for curve fittings revealed a different curve compared to reported normal values in the general populations. AFP was not detected in any of the IH samples examined at either the transcriptional or translational levels. CONCLUSION: This study demonstrates the association of proliferating IH with elevated serum levels of AFP, which normalized following surgical excision or propranolol treatment. We have shown that IH is not the direct source of AFP. An interaction between the primitive mesoderm-derived IH and the endogenous endodermal tissues, such as the liver, via an intermediary, may explain the elevated serum levels of AFP in infants with extrahepatic IH. PMID- 26904546 TI - The Role of Femoroacetabular Impingement in Core Muscle Injury/Athletic Pubalgia: Diagnosis and Management. AB - Chronic groin pain in athletes represents a major diagnostic and therapeutic challenge in sports medicine. Two recognized causes of inguinal pain in the young adult athlete are core muscle injury/athletic pubalgia (CMI/AP) and femoroacetabular impingement (FAI). CMI/AP and FAI were previously considered to be two distinct entities; however, recent studies have suggested both entities to frequently coincide in the athlete with groin pain. This article briefly discusses the role of FAI in CMI/AP and the diagnosis and management of this complex disease. PMID- 26904547 TI - Verrucous Carcinoma of the Vulva: A Case Report and Review of the Literature. AB - Verrucous carcinoma of the vulva is a rare lesion (1). Affecting essentially postmenopausal women, this lesion is a distinct and particular entity in vulval carcinoma classification and its scalability is uncertain and unpredictable. Here, we present a case concerning a 48-year-old patient, without follow-up after a condyloma acuminate of the vulva (large left lip). The origin of this case will be discussed in this article. The treatment decided was only surgical. A review of literature shows the rarity of this lesion of the female genital tract. PMID- 26904548 TI - Constraint Based Modeling Going Multicellular. AB - Constraint based modeling has seen applications in many microorganisms. For example, there are now established methods to determine potential genetic modifications and external interventions to increase the efficiency of microbial strains in chemical production pipelines. In addition, multiple models of multicellular organisms have been created including plants and humans. While initially the focus here was on modeling individual cell types of the multicellular organism, this focus recently started to switch. Models of microbial communities, as well as multi-tissue models of higher organisms have been constructed. These models thereby can include different parts of a plant, like root, stem, or different tissue types in the same organ. Such models can elucidate details of the interplay between symbiotic organisms, as well as the concerted efforts of multiple tissues and can be applied to analyse the effects of drugs or mutations on a more systemic level. In this review we give an overview of the recent development of multi-tissue models using constraint based techniques and the methods employed when investigating these models. We further highlight advances in combining constraint based models with dynamic and regulatory information and give an overview of these types of hybrid or multi level approaches. PMID- 26904549 TI - There is Diversity in Disorder-"In all Chaos there is a Cosmos, in all Disorder a Secret Order". AB - The protein universe consists of a continuum of structures ranging from full order to complete disorder. As the structured part of the proteome has been intensively studied, stably folded proteins are increasingly well documented and understood. However, proteins that are fully, or in large part, disordered are much less well characterized. Here we collected NMR chemical shifts in a small database for 117 protein sequences that are known to contain disorder. We demonstrate that NMR chemical shift data can be brought to bear as an exquisite judge of protein disorder at the residue level, and help in validation. With the help of secondary chemical shift analysis we demonstrate that the proteins in the database span the full spectrum of disorder, but still, largely segregate into two classes; disordered with small segments of order scattered along the sequence, and structured with small segments of disorder inserted between the different structured regions. A detailed analysis reveals that the distribution of order/disorder along the sequence shows a complex and asymmetric distribution, that is highly protein-dependent. Access to ratified training data further suggests an avenue to improving prediction of disorder from sequence. PMID- 26904550 TI - Does Early Environmental Complexity Influence Tyrosine Hydroxylase in the Chicken Hippocampus and "Prefrontal" Caudolateral Nidopallium? AB - In adult chickens, the housing system influences hippocampal morphology and neurochemistry. However, no work has been done investigating the effects of the early life environment on chicken brain development. In the present study, we reared 67 commercial laying hens (Gallus gallus domesticus) in two environments that differed in the degree of complexity (aviary or cage system). These two groups were further divided into two age groups. At 20 weeks of age, 18 aviary reared birds and 15 cage-reared birds were humanely euthanized and their brains dissected. At 24 weeks of age, a further 16 brains from aviary-reared birds and 18 brains from cage-reared birds were collected. These brains were prepared for immunohistochemical detection of tyrosine hydroxylase (TH), the rate-limiting enzyme in the biosynthesis of dopamine, in the hippocampus and the caudolateral nidopallium (NCL). There were no differences between the treatment groups in TH staining intensity in the hippocampus or the NCL. In the medial hippocampus, the right hemisphere had higher TH staining intensity compared to the left hemisphere. The opposite was true for the NCL, with the left hemisphere being more strongly stained compared to the right hemisphere. The present study supports the notion that the hippocampus is functionally lateralized, and our findings add to the body of knowledge on adult neural plasticity of the avian brain. PMID- 26904551 TI - Developmental Structural Tooth Defects in Dogs - Experience From Veterinary Dental Referral Practice and Review of the Literature. AB - Developmental tooth abnormalities in dogs are uncommon in general veterinary practice but understanding thereof is important for optimal management in order to maintain masticatory function through preservation of the dentition. The purpose of this review is to discuss clinical abnormalities of the enamel and general anatomy of dog teeth encountered in veterinary dental referral practice and described in the literature. More than 900 referral cases are seen annually between the two referral practices. The basis of the pathogenesis, resultant clinical appearance, and the principles of management for each anomaly will be described. Future research should be aimed toward a more detailed analysis of these conditions so rarely described in the literature. PMID- 26904552 TI - Retinoids in the pancreas. AB - Retinoids (vitamin A and its natural and synthetic analogs) are required by most tissues for maintaining the normal health of the tissue. This is certainly true for the pancreas. The recent literature is convincing that retinoids are needed by the adult to assure normal pancreatic endocrine functions, especially those of the alpha- and beta-cells. It is also well established that retinoids are required to insure normal pancreas development in utero, including the development of the endocrine pancreas. The actions of retinoids for maintaining normal pancreatic islet functions has drawn considerable research interest from investigators interested in understanding and treating metabolic disease. Pancreatic retinoids are also of interest to investigators studying the origins of pancreatic disease, including the development of pancreatic fibrosis and its sequelae. This research interest is focused on pancreatic stellate cells (PSCs) which store retinoids and possess the metabolic machinery needed to metabolize retinoids. The literature on pancreatic disease and retinoids suggests that there is an association between impairments in pancreatic retinoid storage and metabolism and the development of pancreatic disease. These topics will be considered in this review. PMID- 26904554 TI - Deletion of tumor progression locus 2 attenuates alcohol-induced hepatic inflammation. AB - BACKGROUND: The pathogenesis of alcoholic liver disease (ALD) involves the interaction of several inflammatory signaling pathways. Tumor progression locus 2 (TPL2), also known as Cancer Osaka Thyroid (COT) and MAP3K8, is a serine threonine kinase that functions as a critical regulator of inflammatory pathways by up-regulating production of inflammatory cytokines. The present study aims to fill the gap in knowledge regarding the involvement of TPL2 in the mechanism of alcohol-induced hepatic inflammation. METHODS: Male TPL2(-/-) knockout (TPL2KO) mice and TPL2(+/+) wild-type (WT) mice were group pair-fed with Lieber-DeCarli liquid ethanol diet (EtOH diet, 27% energy from EtOH) or control diet (ctrl diet) for 4 weeks. Both histological and molecular biomarkers involved in the induction of hepatic inflammation by alcohol consumption were examined. RESULTS: Consumption of the EtOH diet in WT mice lead to a significant induction of TPL2 mRNA expression as compared with WT mice fed ctrl diet. A significant induction in inflammatory foci and steatosis was also observed in WT mice fed EtOH diet. The deletion of TPL2 significantly reduced inflammatory foci in the liver of mice consuming both ctrl and EtOH diets as compared to their respective WT controls. This reduction was associated with suppression of hepatic inflammatory gene expression of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta) and macrophage marker F4/80. In addition, histological analysis of livers revealed that TPL2 deletion resulted in reduced steatosis in both ctrl (significant) and EtOH (non-significant) diet-fed mice as compared to their respective WT controls. CONCLUSIONS: The demonstration that TPL2 deletion attenuates alcohol-induced hepatic inflammation provides evidence of a novel role for TPL2 in the pathogenesis of ALD. PMID- 26904553 TI - Retinol as electron carrier in redox signaling, a new frontier in vitamin A research. AB - Nature uses carotenoids and retinoids as chromophores for diverse energy conversion processes. The key structural feature enabling the interaction with light and other manifestations of electro-magnetism is the conjugated double-bond system that all members of this superfamily share in common. Among retinoids, retinaldehyde alone was long known as the active chromophore of vision in vertebrates and invertebrates, as well of various light-driven proton and ion pumps in Archaea. Until now, vitamin A (retinol) was solely regarded as a biochemical precursor for bioactive retinoids such as retinaldehyde and retinoic acid (RA), but recent results indicate that this compound has its own physiology. It functions as an electron carrier in mitochondria. By electronically coupling protein kinase Cdelta (PCKdelta) with cytochrome c, vitamin A enables the redox activation of this enzyme. This review focuses on the biochemistry and biology of the PCKdelta signaling system, comprising PKCdelta, the adapter protein p66Shc, cytochrome c and retinol. This complex positively regulates the conversion of pyruvate to acetyl-coenzyme A (CoA) by the pyruvate dehydrogenase enzyme. Vitamin A therefore plays a key role in glycolytic energy generation. The emerging paradigm of retinol as electron-transfer agent is potentially transformative, opening new frontiers in retinoid research. PMID- 26904556 TI - Racial disparities in treatment and survival of patients with hepatocellular carcinoma in the United States. AB - BACKGROUND: While the incidence and mortality of hepatocellular carcinoma (HCC) continue to increase across the United States (US), disparities may exist relative to treatment modality and survival. The objective of the present study was to determine the factors associated with racial differences in survival among patients with HCC in the US. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients with HCC between 1998 and 2012 in the US. Multivariable logistic regression analysis was performed to examine associations between type of therapy and race, while a multivariable Cox proportional hazards model was built to determine the effect of race on survival. RESULTS: A total of 58,186 patients with HCC were identified. Over two-thirds of patients were white (n=39,223, 67.4%), while 18.3% were Asian (n=10,665), 13.1% black (n=7,620) and 1.2% native American (n=678). In comparison to other racial groups, Asian patients with HCC tended to be older [white vs. black vs. native American vs. Asian: median age: 63 years, interquartile range (IQR), 55-73 vs. 59 years, IQR, 53-66 vs. 59 years, IQR, 53-69 vs. 64 years, IQR, 55-73, P<0.001] and were diagnosed with larger tumors (white vs. black vs. native American vs. Asian: median tumor size: 4.8 cm, IQR, 3.0-8.0 vs. 5.1 cm, IQR, 3.1-8.7 vs. 4.8 cm, IQR, 3.0-7.3 vs. 5.5 cm, IQR, 3.1-9.0, P<0.001). Asian patients were also less likely to present with concomitant cirrhosis (white vs. black vs. native American vs. Asian: 81.8% vs. 77.7% vs. 83.2% vs. 69.1%, P<0.001) while elevated levels of alpha-fetoprotein more were often noted among black patients (white vs. black vs. native American vs. Asian: 25.5% vs. 14.9% vs. 22.2% vs. 21.8%, P<0.001). Compared to other racial groups, Asian patients were most likely to receive any form of treatment (white vs. black vs. native American vs. Asian: 29.2% vs. 25.2% vs. 27.6% vs. 34.4%, P<0.001). In particular, after controlling for potential confounders, Asian patients demonstrated the greatest odds of undergoing surgery (OR: 1.48, 95% CI, 1.13-1.95, P=0.01). The median overall survival (OS) was 11 months with the worst prognosis noted among black patients. After accounting for disease and patient factors, Asian patients demonstrated the lowest risk for death [hazard ratio (HR): 0.76, 95% CI, 0.66-0.87, P<0.001] while no differences were noted in the risk of death among other racial groups (all P>0.05). CONCLUSIONS: Significant racial differences were noted in presentation, treatment and survival among patients with HCC. Further research is necessary to better understand socio-demographic and biological factors driving racial disparities in care. Future policies should aim to improve access to care among racial/ethnic minorities. PMID- 26904555 TI - Does diabetes mellitus affect presentation, stage and survival in operable pancreatic cancer? AB - BACKGROUND: The aim of the study is to investigate differences in clinical presentation, disease stage and survival of operable pancreatic cancer patients with new onset DM compared to long standing diabetes mellitus (DM) and non diabetics. METHODS: A prospectively maintained pancreatic cancer surgery database of a tertiary care teaching hospital from January 2006 to August 2012 was reviewed. Only patients with a histological diagnosis of pancreatic carcinoma (PC) were included in final analysis. DM was defined as HbA1c >6.5% or any patient on anti-diabetic treatment regardless of HbA1c value. New onset DM was defined when diagnosed within two preceding years of surgery. Patients were stratified into two groups: DM and non DM. Among the DM patients, patients with new onset DM were further stratified and studied separately. Staging of PC was performed according to the 6(th) edition of AJCC. Survival of patients with PC was determined by reviewing medical records. Patients and their families were contacted if there was no existing follow-up. RESULTS: Eighty-six patients (n=55, 63.9% male) with a mean age of 62 years (range, 29-85 years) underwent pancreatic cancer surgery during the study period. Of the 86 patients, 30 (34%) had DM of which eight patients (9% overall) had new onset DM. DM patients tended to be older compared to non DM patients (67.8 vs. 58.5 years, P=0.0005). The majority of non DM patients were symptomatic (98.2%), and there was a tendency for DM group patients to be asymptomatic at presentation (13.3% vs. 1.8%, P=0.05). Abdominal pain was less common in DM patients compared to non DM patients (30% vs. 53.6%, P=0.04). The median duration of new onset DM prior to diagnosis of PC was 2 months (range, 1-23 months). There was a tendency for DM patients to present at an early stage (stage I and stage II) (P=0.08). There was no difference in survival (P=0.17) for new onset DM compared to long standing DM and non DM patients. CONCLUSIONS: DM patients tend to be older and are less likely to present with abdominal pain. Asymptomatic presentation and early stage disease tends to occur in DM patients. A larger sample size is required to determine if survival of new onset DM patients differs from long standing and non DM patients. PMID- 26904557 TI - Surgery for gallstone disease during pregnancy does not increase fetal or maternal mortality: a meta-analysis. AB - BACKGROUND: Pregnancy was traditionally considered a contraindication to cholecystectomy but is now becoming the favoured option for gallstone-related disease (GRD) during pregnancy. METHODS: To assess if cholecystectomy during pregnancy increases the risk of preterm labour, fetal mortality and maternal mortality. PubMed and MEDLINE databases for the period from January 1966 through December 2013. Studies were both conservative and surgical intervention was utilised in the management of GRD were included. The results of the included studies were pooled using meta-analysis techniques. RESULTS: Surgical intervention for GRD in pregnancy does not increase the risk of preterm labour, fetal mortality or maternal mortality. CONCLUSIONS: Cholecystectomy during pregnancy for GRD is associated with low complications for the fetus and mother and should be considered in all suitable patients. PMID- 26904559 TI - Carcinosarcoma of the bile duct: a case report and review of literature. AB - Carcinosarcomas of the bile ducts are very rare tumors consisting of both epithelial and mesenchymal elements. We report a case of bile duct carcinosarcoma and its clinical, radiological and pathological features and a brief review on this rare condition. PMID- 26904558 TI - How much ischemia can the liver tolerate during resection? AB - The use of vascular inflow occlusion (VIO, also known as the Pringle maneuver) during liver surgery prevents severe blood loss and the need for blood transfusion. The most commonly used technique for VIO entails clamping of the portal triad, which simultaneously occludes the proper hepatic artery and portal vein. Although VIO is an effective technique to reduce intraoperative blood loss, it also inevitably inflicts hepatic ischemia/reperfusion (I/R) injury as a side effect. I/R injury induces formation of reactive oxygen species that cause oxidative stress and cell death, ultimately leading to a sterile inflammatory response that causes hepatocellular damage and liver dysfunction that can result in acute liver failure in most severe cases. Since the duration of ischemia correlates positively with the severity of liver injury, there is a need to find the balance between preventing severe blood loss and inducing liver damage through the use of VIO. Although research on the maximum duration of hepatic ischemia has intensified since the beginning of the 1980s, there still is no consensus on the tolerable upper limit. Based on the available literature, it is concluded that intermittent and continuous VIO can both be used safely when ischemia times do not exceed 120 min. However, intermittent VIO should be the preferred technique in cases that require >120 min duration of ischemia. PMID- 26904561 TI - From nasal drainage tubes to biliary and pancreatic stents. PMID- 26904560 TI - Minimally invasive management of intrahepatic type II gallbladder perforation: a case report. AB - Intrahepatic gallbladder perforation (GBP) is a rare medical entity, which creates a cholecystohepatic communication. We describe the case of a 70-year-old patient who presented with abdominal pain and a Niemeier type II GBP. This case report illustrates the minimally invasive management of a rare and life threatening pathology. PMID- 26904563 TI - Professor Ho-Seong Han: enjoy being a surgeon. PMID- 26904562 TI - Organ-specific concept and controversy for premalignant lesions and carcinogenesis of gallbladder cancer. AB - An analysis of premalignant lesions, risk factors and models of carcinogenesis of gallbladder cancer (GBC) involves the concept of organ specificity. In GBC, the dysplasia-carcinoma sequence and metaplasia-dysplasia-carcinoma sequence are considered to be more important models of carcinogenesis than the adenoma carcinoma sequence. Cholecystectomy is recommended for gallbladder polyps >=1.0 cm, and all pre-invasive adenomas and papillary neoplasms >=1.0 cm are defined as intracholecystic papillary-tubular neoplasms (ICPTNs). Although adenomyomatosis (ADM) and xanthogranulomatous cholecystitis (XGC) are controversial lesions, a knowledge of their clinicopathological features would help clinicians to manage gallbladder lesions associated with ADM or XCG. PMID- 26904564 TI - STARD guidelines: another piece of an intricate puzzle for evaluating the quality of scientific publishing. PMID- 26904565 TI - Improving accuracy of diagnostic studies in a world with limited resources: a road ahead. PMID- 26904566 TI - The standards for reporting diagnostic accuracy studies 2015 update: is there a missing link to the triumvirate? PMID- 26904567 TI - A STAR-Document for those interested in evaluating diagnostic research studies. PMID- 26904568 TI - STARD guideline in diagnostic accuracy tests: perspective from a systematic reviewer. PMID- 26904569 TI - Enhancing radiotherapy: breaking free from undue zeal for the existent, and utter contempt for the prospective. PMID- 26904570 TI - Prospective randomized study comparing concomitant chemoradiotherapy using weekly cisplatin & paclitaxel versus weekly cisplatin in locally advanced carcinoma cervix. AB - BACKGROUND: To evaluate the benefit with the addition of paclitaxel to cisplatin based concurrent chemoradiotherapy (C-CRT) for the treatment of locally advanced carcinoma of the uterine cervix in terms of local control, disease free survival (DFS) and overall survival (OS). METHODS: From 1/7/2011 to 31/5/2012, 81 women (median age of 50 years) with newly diagnosed, histopathologically proven carcinoma cervix with FIGO stages IIA to IIIB were randomized to two arms cisplatin 40 mg/m(2)/week for 5 weeks was given in single agent cisplatin (control arm), while cisplatin 30 mg/m(2)/week and paclitaxel 50 mg/m(2)/week for 5 weeks were given in cisplatin and paclitaxel (study arm). External beam radiotherapy (EBRT) was delivered to a total dose of 50 Gray (Gy) in 25 fractions (#) followed by intracavitary (I/C) brachytherapy or supplement EBRT at 20 Gy/10# with 2 cycles of respective chemotherapy. This prospective trial was registered with clinicaltrials.gov (NCT01593306). RESULTS: Patients (n=81) had a maximum follow up of 36 months with a median follow up of 29 months. At first follow up study arm showed complete response in 84% vs. 75.6% in control arm (P=0.4095). An increase in toxicities was observed in the study arm in comparison to the control arm in terms of haematological grade II (35% vs. 12.2%), gastrointestinal (GI) grade III (20% vs. 7.4%) and GI grade IV (12.5% vs. 2.4%) toxicities. At median follow-up, the study arm demonstrated enhanced outcomes over the control arm in terms of DFS (79.5% vs. 64.3%; P=0.07) and OS (87.2% vs. 78.6%; P=0.27). CONCLUSIONS: Despite the expected increase in manageable toxicities, these early results reveal promise with the inclusion of paclitaxel into the standard cisplatin based chemoradiation regime. Larger multi-institutional studies are justified to confirm a potential for the enhancement of response rates and survival. PMID- 26904573 TI - Immunological interactions in radiotherapy-opening a new window of opportunity. AB - After a span of significant developments & advances we have reached a plateau in all the oncological disciplines in last decade. Escalation of dose of radiotherapy (RT) became possible with emergence of intensity modulated radiotherapy (IMRT) and image guided radiotherapy (IGRT). Different radiosensitizing agents starting from conventional cytotoxic drugs to hypoxic radiosensitizers have been tried to increase the effect of RT. However technological advancement hasn't been translated into significant clinical benefits. Exploiting the immune system to enhance the effect of RT is a relatively new concept and a fast growing area in the field of oncology. RT cannot longer be considered as a localized treatment, but rather as a systemic weapon for solid tumors. The phenomenon of abscopal effect, meaning the action of RT upon distant 'out-of-field' foci of malignancies has been a major focus of recent research, and holds great promise for the future. In this review article we are going to discuss the immunological interactions in RT and its promising clinical implications. PMID- 26904571 TI - Novel agents and treatment techniques to enhance radiotherapeutic outcomes in carcinoma of the uterine cervix. AB - BACKGROUND: Survival of patients with locally advanced carcinoma cervix (LACC) using the current standard of concurrent chemo-radiotherapy (CCRT) has reached a plateau over the last two decades. Loco-regional failure in first two years of treatment completion and distant metastasis in the subsequent years has put the survival curves at a halt. Strategies of induction and adjuvant chemotherapy have yielded little as has any advancement in techniques of delivery of radiation therapy. This article aims at discussing the current existing literature as well as promising novel strategies to enhance radiotherapeutic outcomes in carcinoma of the uterine cervix. METHODS: The review of English literature included phase I III trials evaluating either a novel agent, novel application/modifications of an existing treatment regimen or an innovative treatment technique. The studies have been divided in to subsections with summary of most important findings at the end of each section. RESULTS: Despite CCRT being the 'gold standard' treatment, several issues like optimum drug combination, schedule of drug delivery, combination with molecular targeted agents etc. remain undefined. Taxane, topoisomerase and gemcitabine based regimen needs to be further explored and compared with cisplatin based CCRT regimen. Several approaches like local delivery of cytotoxic agents, use of nano-medicine with CCRT are appearing on horizon with promises for the future. Therapies need to be designed based on the human papillomavirus titers of the patients and incorporation of radiosensitizers as an effective way of palliation with short course of radiotherapy may further enhance the radiotherapeutic outcomes. CONCLUSIONS: The results of the studies with novel agents and treatment techniques appear promising. Further research in this arena including incorporation of cost-effectiveness analysis and quality of life issues in future trial designs are warranted. PMID- 26904572 TI - Molecular targeted therapy to improve radiotherapeutic outcomes for non-small cell lung carcinoma. AB - Effective treatments for non-small cell lung carcinoma (NSCLC) remain elusive. The use of concurrent chemotherapy with radiotherapy (RT) has improved outcomes, but a significant proportion of NSCLC patients are too frail to be able to tolerate an intense course of concurrent chemoradiotherapy. The development of targeted therapies ignited new hope in enhancing radiotherapeutic outcomes. The use of targeted therapies against the epidermal growth factor receptor (EGFR) has offered slight but significant benefits in concurrent use with RT for certain patients in certain situations. However, despite theoretical promise, the use of anti-angiogenics, such as bevacizumab and endostatin, has not proven clinically safe or useful in combination with RT. However, many new targeted agents against new targets are being experimented for combined use with RT. It is hoped that these agents may provide a significant breakthrough in the radiotherapeutic management of NSCLC. The current review provides a brief discussion about the targets, the targeted therapies, the rationale for the use of targeted therapies in combination with RT, and a brief review of the existing data on the subject. PMID- 26904574 TI - Chemically enhanced radiotherapy: visions for the future. AB - Radiotherapy (RT) is an important part of cancer management, with more than a third of all cancer cures being attributable to RT. Despite the advances in RT over the past century, the overall outcomes in a majority of malignancies are still unsatisfactory. There has been a constant endeavor to enhance the outcome of RT, and this has been in the form of altered fractionation, oxymimetic radiosensitizers, the use of concurrent chemotherapy, anti-angiogenic therapy and anti-growth factor receptor targeted therapies. This article presents a vision for the future, with emphasis upon emerging prospects which could enhance RT outcomes. Positive speculations regarding the use of immunological aspects, the use of nanoscale technology and the adoption of metronomic concurrent chemotherapy have been presented. Also, the potential with the use of low dose hyperradiosensitivity in enhancing chemotherapy outcomes too has been discussed. In this era of evidence based clinical practise, there exists a strong obsession towards the 'present' with 'contempt towards the future'. Accepting the shortcomings of the existing modalities, there must be a strong zeal towards discovering better methodologies to enhance radiotherapeutic outcomes for the sake of a better future. PMID- 26904575 TI - Newer positron emission tomography radiopharmaceuticals for radiotherapy planning: an overview. AB - Positron emission tomography-computed tomography (PET-CT) has changed cancer imaging in the last decade, for better. It can be employed for radiation treatment planning of different cancers with improved accuracy and outcomes as compared to conventional imaging methods. (18)F-fluorodeoxyglucose remains the most widely used though relatively non-specific cancer imaging PET tracer. A wide array of newer PET radiopharmaceuticals has been developed for targeted imaging of different cancers. PET-CT with such new PET radiopharmaceuticals has also been used for radiotherapy planning with encouraging results. In the present review we have briefly outlined the role of PET-CT with newer radiopharmaceuticals for radiotherapy planning and briefly reviewed the available literature in this regard. PMID- 26904577 TI - Radiotherapy to volumes defined by metabolic imaging in gliomas: time to abandon monstrous margins? AB - The survival in patients with high grade gliomas (HGG) remains poor even after the adoption post-operative radiotherapy (RT) to magnetic resonance imaging (MRI) based volumes. Despite delivery of 'standardized' doses of radiation, recurrence is the norm, rather than the exception. Recurrences occur both within, and outside of the volume of irradiation, leading us to two questions-firstly concerning the adequacy of the dose of radiation used, and secondly about the current methods of treatment volume delineation. The emergence of newer radiopharmaceuticals for use in positron emission tomography (PET) have kindled the hope of more precise volume localizations for post-operative RT, and it is likely that these new radiopharmaceuticals can help us define accurate areas at highest risk of recurrence and thus allow us to use increased doses of radiation with confidence. PMID- 26904576 TI - Concurrent therapy to enhance radiotherapeutic outcomes in glioblastoma. AB - Glioblastoma is one of the most fatal and incurable human cancers characterized by nuclear atypia, mitotic activity, intense microvascular proliferation and necrosis. The current standard of care includes maximal safe surgical resection followed by radiation therapy (RT) with concurrent and adjuvant temozolomide (TMZ). The prognosis remains poor with median survival of 14.6 months with RT plus TMZ. Majority will have a recurrence within 2 years from diagnosis despite adequate treatment. Radiosensitizers, radiotherapy dose escalation and altered fractionation have failed to improve outcome. The molecular biology of glioblastoma is complex and poses treatment challenges. High rate of mutation, genotypic and phenotypic heterogeneity, rapid development of resistance, existence of blood-brain barrier (BBB), multiple intracellular and intercellular signalling pathways, over-expression of growth factor receptors, angiogenesis and antigenic diversity renders the tumor cells differentially susceptible to various treatment modalities. Thus, the treatment strategies require personalised or individualized approach based on the characteristics of tumor. Several targeted agents have been evaluated in clinical trials but the results have been modest despite these advancements. This review summarizes the current standard of care, results of concurrent chemoradiation trials, evolving innovative treatments that use targeted therapy with standard chemoradiation or RT alone, outcome of various recent trials and future outlook. PMID- 26904578 TI - Multiple imputation for time series data with Amelia package. AB - Time series data are common in medical researches. Many laboratory variables or study endpoints could be measured repeatedly over time. Multiple imputation (MI) without considering time trend of a variable may cause it to be unreliable. The article illustrates how to perform MI by using Amelia package in a clinical scenario. Amelia package is powerful in that it allows for MI for time series data. External information on the variable of interest can also be incorporated by using prior or bound argument. Such information may be based on previous published observations, academic consensus, and personal experience. Diagnostics of imputation model can be performed by examining the distributions of imputed and observed values, or by using over-imputation technique. PMID- 26904579 TI - A case of immunoglobulin G4-related constrictive pericarditis. AB - A 47-year-old man was admitted with a complaint of upper abdominal distension and shortness of breath. The constrictive pericarditis was diagnosed based on the transthoracic echocardiogram (TTE) and chest CT scan. Pathology revealed it is immunoglobulin (Ig) G4-related constrictive pericarditis. Likely, this is the first case of IgG4-related constrictive pericarditis reported in China. PMID- 26904580 TI - (18)F-FDG PET/CT in multicentric Castleman disease: a case report. AB - Castleman disease (CD) is a chronic lymphoproliferative disorder characterized by unexplained enlarged lymph nodes. According to lymph nodes distribution it contains two types of single-centric and multicentric (more than one site) disease. Multicentric Castleman disease (MCD) is rare, and shows unspecific manifestation with high misdiagnosis rate. Here we reported a case of MCD in a 43 year-old male. (18)F-FDG PET/CT imaging demonstrated higher FDG uptake in multiple lymph nodes and slightly FDG uptake in spleen and bone marrow. Right inguinal Lymph node biopsy was taken and the results confirmed CD. PMID- 26904581 TI - The impact of preanalytical variability in clinical trials: are we underestimating the issue? PMID- 26904582 TI - STING-cytosolic DNA sensing: the backbone for an effective tumor radiation therapy. PMID- 26904583 TI - Treatment options and outcomes for lower pole stone management: are we there yet? PMID- 26904584 TI - Venous-to-arterial carbon dioxide differences and the microcirculation in sepsis. PMID- 26904585 TI - Intra-articular platelet-rich plasma for the treatment of osteoarthritis. PMID- 26904586 TI - Prevalence of Antipsychotic Polypharmacy and Associated Factors among Outpatients with Schizophrenia Attending Amanuel Mental Specialized Hospital, Addis Ababa, Ethiopia. AB - Background. Despite recommendations by guidelines to avoid combinations of antipsychotics unless after multiple trials of antipsychotic monotherapy, it is quite a common practice to use combinations. This practice leads to unnecessary expenses and exposes the patient to severe drug adverse effects. Methods. An institution based cross-sectional study was conducted from April to May 2014. Systematic random sampling technique was used to select 423 study subjects. Logistic regression analysis was conducted to identify associated factors of antipsychotic polypharmacy among schizophrenia outpatients. Result. The overall prevalence of antipsychotic polypharmacy was found to be 28.2%. Extra pyramidal side effects (AOR = 2.80; 95% CI: 1.38, 5.71), repeated psychiatric hospitalization (AOR = 2.83; 95% CI: 1.45, 5.50), history of substance use (AOR = 2.82; 95% CI: 1.36, 5.88), longer duration of treatment (AOR = 2.10; 95% CI: 1.14, 3.87), and drug nonadherence (AOR = 1.84; 95% CI: 1.14, 2.98) were found to be significantly associated with antipsychotic polypharmacy. Conclusion. Prevalence of antipsychotic polypharmacy was found to be high among the current study participants. Individuals who had extra pyramidal side effects, admission, substance use, duration of treatment, and drug nonadherence were associated with antipsychotic polypharmacy. PMID- 26904587 TI - Psychometric Validation of the Bangla Version of the Patient-Doctor Relationship Questionnaire. AB - Background. The patient-doctor relationship is an important issue in health care as it is linked to patient satisfaction, treatment adherence, and treatment outcome. The PDRQ-9 is brief instrument which has an excellent overall internal consistency to measure it. Objective. It was aimed at developing a culturally adapted and validated Bangla version of Patient-Doctor Relationship Questionnaire (PDRQ-9). Method. Data were collected during the period of May 2015 to July 2015 from 50 patients by interviewing with the final Bangla version of PDRQ-9 obtained by ideal translation-back translation procedure with nonprobability purposive consecutive sampling and analyzed by Statistical Package of Social Science (SPSS) 16.0 and Microsoft Excel 2007 version software. Result. The internal consistency of Bangla PDRQ-9 was measured by Cronbach's alpha which was 0.97. Only one factor was extracted from varimax rotation factor analysis with high commonalities between the items. Conclusion. Bangla version of PDRQ-9 is valid, accepted, and widely applicable in clinical practice, research, public health, and primary health care in Bangladesh. PMID- 26904588 TI - Angiotensin I-Converting Enzyme Inhibitory Peptides of Chia (Salvia hispanica) Produced by Enzymatic Hydrolysis. AB - Synthetic angiotensin I-converting enzyme (ACE-I) inhibitors can have undesirable side effects, while natural inhibitors have no side effects and are potential nutraceuticals. A protein-rich fraction from chia (Salvia hispanica L.) seed was hydrolyzed with an Alcalase-Flavourzyme sequential system and the hydrolysate ultrafiltered through four molecular weight cut-off membranes (1 kDa, 3 kDa, 5 kDa, and 10 kDa). ACE-I inhibitory activity was quantified in the hydrolysate and ultrafiltered fractions. The hydrolysate was extensive (DH = 51.64%) and had 58.46% ACE-inhibitory activity. Inhibition ranged from 53.84% to 69.31% in the five ultrafiltered fractions and was highest in the <1 kDa fraction (69.31%). This fraction's amino acid composition was identified and then it was purified by gel filtration chromatography and ACE-I inhibition measured in the purified fractions. Amino acid composition suggested that hydrophobic residues contributed substantially to chia peptide ACE-I inhibitory strength, probably by blocking angiotensin II production. Inhibitory activity ranged from 48.41% to 62.58% in the purified fractions, but fraction F1 (1.5-2.5 kDa) exhibited the highest inhibition (IC50 = 3.97 MUg/mL; 427-455 mL elution volume). The results point out the possibility of obtaining bioactive peptides from chia proteins by means of a controlled protein hydrolysis using Alcalase-Flavourzyme sequentional system. PMID- 26904589 TI - Effect of Cholesterol Removal Processing Using beta -Cyclodextrin on Main Components of Milk. AB - Various concentrations (0%, 0.5%, 1% and 1.5%) of beta-CD were mixed with different fat contents (1%, 2.5% and 3%) of raw (unhomogenized) and homogenized milk at two mixing temperatures of 8 and 20 degrees C. The cholesterol residue, fat, protein, lactose, solid nonfat (SNF), density, and ash content of milk were measured for each treatment. The results statistically analysed and showed that the cholesterol content of milk remarkably decreased as the beta-CD was increased particularly in homogenized milk at 20 degrees C. However, the reduction rate of cholesterol was decreased when extra beta-CD was added due to its intermolecular reactions. The maximum cholesterol reduction was achieved at the level of 1% beta CD. The fat content, SNF, protein, lactose, and density content were decreased with increasing beta-CD whereas it did not affect ash content. PMID- 26904590 TI - The Influence of Interfering Substances on the Antimicrobial Activity of Selected Quaternary Ammonium Compounds. AB - Standard cleaning processes may not remove all the soiling typically found in food industry, such as carbohydrates, fats, or proteins. Contaminants have a high impact in disinfection as their presence may reduce the activity of disinfectants. The influence of alginic acid, bovine serum albumin, yeast extract, and humic acids was assessed on the antimicrobial activities of benzalkonium chloride and cetyltrimethyl ammonium bromide against Bacillus cereus vegetative cells and Pseudomonas fluorescens. The bacteria (single and consortium) were exposed to surfactants (single and combined) in the absence and presence of potential disinfection interfering substances. The antimicrobial effects of the surfactants were assessed based on the bacterial respiratory activity measured by oxygen uptake rate due to glucose oxidation. The tested surfactants were efficient against both bacteria (single and consortium) with minimum bactericidal concentrations ranging from 3 to 35 mg.L(-1). The strongest effect was caused by humic acids that severely quenched antimicrobial action, increasing the minimum bactericidal concentration of the surfactants on P. fluorescens and the consortium. The inclusion of the other interfering substances resulted in mild interferences in the antibacterial activity. This study clearly demonstrates that humic acids should be considered as an antimicrobial interfering substance in the development of disinfection strategies. PMID- 26904591 TI - Polyphenol Bioaccessibility and Sugar Reducing Capacity of Black, Green, and White Teas. AB - Tea (Camellia sinensis) is a widely consumed beverage and recognised for its potential enhancing effect on human health due to its rich polyphenol content. While a number of studies have investigated the quantity and type of polyphenols present in different tea samples, no study has reported the potential effect of digestive enzymes on the availability of tea polyphenols for human absorption or the subsequent impact on glycaemic response. The objectives of the present study were to assess the total polyphenol content of different teas, to assess the bioaccessibility of polyphenols in whole and bagged teas, and to determine the effect of black, white, and green tea infusions on sugar release. All of the teas were a significant source of polyphenols (10-116 mg Gallic acid equivalents/g). There was an overall increase in the release of polyphenols from both the bagged and the whole teas following in vitro digestion. Bagged green tea significantly (P < 0.05) reduced rapidly digestible starch from white bread samples compared to control and black and white bagged teas. The present study confirms that tea is a rich source of polyphenols and highlights the potential benefits it may have on modulating glycaemic response in humans. PMID- 26904592 TI - Comparative Effect of Crude and Commercial Enzyme on the Juice Recovery from Bael Fruit (Aegle marmelos Correa) Using Principal Component Analysis. AB - The effect of incubation time, incubation temperature, and crude enzyme concentration was observed on the yield, viscosity, and clarity of the juice obtained from bael fruit pulp. The recommended enzymatic treatment conditions from the study were incubation time 475 min, incubation temperature 45 degrees C, and crude enzyme concentration 0.20 mL/25 g bael fruit pulp. The recovery, viscosity, and clarity of the juice under these conditions were 82.9%, 1.41 cps, and 21.32%T, respectively. The variables, clarity, and yield were found as principal components for comparing different samples of the juice treated with enzyme. PMID- 26904593 TI - Sugar Profile, Mineral Content, and Rheological and Thermal Properties of an Isomerized Sweet Potato Starch Syrup. AB - Currently, corn is used to produce more than 85% of the world's high fructose syrup (HFS). There is a search for alternative HFS substrates because of increased food demand and shrinking economies, especially in the developing world. The sweet potato is a feasible, alternative raw material. This study isomerized a high glucose sweet potato starch syrup (SPSS) and determined its sugar profile, mineral content, and rheological and thermal properties. Rheological and thermal properties were measured using a rheometer and DSC, respectively. Sweet potato starch was hydrolyzed to syrup with a mean fructose content of 7.6 +/- 0.4%. The SPSS had significantly higher (P < 0.05) mineral content when compared to commercial ginger and pancake syrups. During 70 days of storage, the SPSS acted as a non-Newtonian, shear-thinning liquid in which the viscosity decreased as shear stress increased. Water loss temperature of the SPSS continually decreased during storage, while pancake and ginger syrups' peak water loss temperature decreased initially and then increased. Further and more detailed studies should be designed to further enhance the fructose content of the syrup and observe its stability beyond 70 days. The SPSS has the potential to be used in human food systems in space and on Earth. PMID- 26904594 TI - Predicting the Quality of Pasteurized Vegetables Using Kinetic Models: A Review. AB - A resurgence in interest examining thermal pasteurization technologies has been driven by demands for "cleaner" labeling and the need of organic and natural foods markets for suitable preventive measures to impede microbial growth and extend shelf life of minimally processed foods and ready-to-eat foods with a concomitant reduction in the use of chemical preservatives. This review describes the effects of thermal pasteurization on vegetable quality attributes including altering flavor and texture to improve consumer acceptability, stabilizing color, improving digestibility, palatability and retaining bioavailability of important nutrients, and bioactive compounds. Here, we provide kinetic parameters for inactivation of viral and bacterial pathogens and their surrogates and marker enzymes used to monitor process effectiveness in a variety of plant food items. Data on thermal processing protocols leading to higher retention and bioactivity are also presented. Thermal inactivation of foodborne viruses and pathogenic bacteria, specifically at lower pasteurization temperatures or via new technologies such as dielectric heating, can lead to greater retention of "fresh like" properties. PMID- 26904595 TI - Effect of Cassava Flour Characteristics on Properties of Cassava-Wheat-Maize Composite Bread Types. AB - Replacement of wheat flour by other kinds of flour in bread making is economically important in South East Africa as wheat is mainly an imported commodity. Cassava is widely available in the region, but bread quality is impaired when large amounts of cassava are used in the bread formulation. Effect of differently processed cassavas (sun-dried, roasted and fermented) on composite cassava-wheat-maize bread quality containing cassava levels from 20 to 40% (w/w) was evaluated in combination with high-methylated pectin (HM-pectin) added at levels of 1 to 3% (w/w) according to a full factorial design. Addition of pectin to cassava flour made it possible to bake bread with acceptable bread quality even at concentration as high as 40%. In addition to cassava concentration, the type of cassava flour had the biggest effect on bread quality. With high level of cassava, bread with roasted cassava had a higher volume compared with sun-dried and fermented. The pectin level had a significant effect on improving the volume in high level roasted cassava bread. Crumb firmness similar to wheat bread could be obtained with sun-dried and roasted cassava flours. Roasted cassava bread was the only bread with crust colour similar to wheat bread. PMID- 26904596 TI - Comparison of Dried Plum Puree, Rosemary Extract, and BHA/BHT as Antioxidants in Irradiated Ground Beef Patties. AB - Fresh ground beef patties with (1) no antioxidant (control), (2) 0.02% butylated hydroxyanisole/butylated hydroxytoluene (BHA/BHT), (3) 3% dried plum puree, or (4) 0.25% rosemary extract were aerobically packaged, irradiated at target doses of 0, 1.5, or 2.0 kGy (1.7 and 2.3 kGy actual doses), and stored at 4 degrees C. The samples were evaluated for lipid oxidation on 0, 3, 7, 14, 21, and 28 days of storage after irradiation. When compared to the control, all antioxidant treatments were effective in retarding (P < 0.05) irradiation-induced lipid oxidation during storage as determined by 2-thiobarbituric acid reactive substances (TBARs) values. Rosemary extracts had the same antioxidant effect (P > 0.05) as BHA/BHT in irradiated and nonirradiated beef patties, followed by the dried plum puree treatment. Irradiation increased TBARs values, but no differences were noted in oxidation between irradiation dose levels. PMID- 26904597 TI - Identification of Imitation Cheese and Imitation Ice Cream Based on Vegetable Fat Using NMR Spectroscopy and Chemometrics. AB - Vegetable oils and fats may be used as cheap substitutes for milk fat to manufacture imitation cheese or imitation ice cream. In this study, 400 MHz nuclear magnetic resonance (NMR) spectroscopy of the fat fraction of the products was used in the context of food surveillance to validate the labeling of milk based products. For sample preparation, the fat was extracted using an automated Weibull-Stoldt methodology. Using principal component analysis (PCA), imitation products can be easily detected. In both cheese and ice cream, a differentiation according to the type of raw material (milk fat and vegetable fat) was possible. The loadings plot shows that imitation products were distinguishable by differences in their fatty acid ratios. Furthermore, a differentiation of several types of cheese (Edamer, Gouda, Emmentaler, and Feta) was possible. Quantitative data regarding the composition of the investigated products can also be predicted from the same spectra using partial least squares (PLS) regression. The models obtained for 13 compounds in cheese (R (2) 0.75-0.95) and 17 compounds in ice cream (R (2) 0.83-0.99) (e.g., fatty acids and esters) were suitable for a screening analysis. NMR spectroscopy was judged as suitable for the routine analysis of dairy products based on milk or on vegetable fat substitutes. PMID- 26904598 TI - Quality Parameters of Six Cultivars of Blueberry Using Computer Vision. AB - Background. Blueberries are considered an important source of health benefits. This work studied six blueberry cultivars: "Duke," "Brigitta", "Elliott", "Centurion", "Star," and "Jewel", measuring quality parameters such as degrees Brix, pH, moisture content using standard techniques and shape, color, and fungal presence obtained by computer vision. The storage conditions were time (0-21 days), temperature (4 and 15 degrees C), and relative humidity (75 and 90%). Results. Significant differences (P < 0.05) were detected between fresh cultivars in pH, degrees Brix, shape, and color. However, the main parameters which changed depending on storage conditions, increasing at higher temperature, were color (from blue to red) and fungal presence (from 0 to 15%), both detected using computer vision, which is important to determine a shelf life of 14 days for all cultivars. Similar behavior during storage was obtained for all cultivars. Conclusion. Computer vision proved to be a reliable and simple method to objectively determine blueberry decay during storage that can be used as an alternative approach to currently used subjective measurements. PMID- 26904599 TI - Polydextrose Enhances Calcium Absorption and Bone Retention in Ovariectomized Rats. AB - Purpose. To evaluate the effect of polydextrose (PDX) on Ca bioavailability and prevention of loss of bone mass. Methods. Twenty-four two-month-old ovariectomized rats were fed three isocaloric diets only varied in fiber source and content up to 60 days (FOS group, a commercial mixture of short- and long chain fructooligosaccharide, OVX group fed AIN 93 diet, and PDX group). A SHAM group was included as control. Apparent Ca absorption percentage (%ABS), changes in total skeleton bone mineral content (tsBMC) and bone mineral density (BMD) and femur BMD, % Bone Volume, Ca and organic femur content, caecal weight, and pH were evaluated. Results. %ABS and caecum weight of PDX and FOS were higher, and caecum pH was lower compared to OVX and SHAM. PDX reached a higher pH and lower caecum weight than FOS possibly because PDX is not completely fermented in the colon. Changes in tsBMC and femur BMD in FOS and PDX were significant lower than SHAM but significantly higher than OVX. % Bone Volume and femur % of Ca in PDX were significantly higher than OVX and FOS but lower than SHAM. Conclusions. PDX increased Ca absorption and prevented bone loss in OVX rats. PMID- 26904600 TI - Enhanced Production of Xylitol from Corncob by Pachysolen tannophilus Using Response Surface Methodology. AB - Optimization of the culture medium and process variables for xylitol production using corncob hemicellulose hydrolysate by Pachysolen tannophilus (MTTC 1077) was performed with statistical methodology based on experimental designs. The screening of nine nutrients for their influence on xylitol production was achieved using a Plackett-Burman design. Peptone, xylose, MgSO4.7H2O, and yeast extract were selected based on their positive influence on xylitol production. The selected components were optimized with Box-Behnken design using response surface methodology (RSM). The optimum levels (g/L) were peptone: 6.03, xylose: 10.62, MgSO4.7H2O: 1.39, yeast extract: 4.66. The influence of various process variables on the xylitol production was evaluated. The optimal levels of these variables were quantified by the central composite design using RSM, for establishment of a significant mathematical model with a coefficient determination of R (2) = 0.91. The validation experimental was consistent with the prediction model. The optimum levels of process variables were temperature (36.56 degrees C), pH (7.27), substrate concentration (3.55 g/L), inoculum size (3.69 mL), and agitation speed (194.44 rpm). These conditions were validated experimentally which revealed an enhanced xylitol yield of 0.80 g/g. PMID- 26904601 TI - Influence of Wheat-Milled Products and Their Additive Blends on Pasta Dough Rheological, Microstructure, and Product Quality Characteristics. AB - This study is aimed to assess the suitability of T. aestivum wheat milled products and its combinations with T. durum semolina with additives such as ascorbic acid, vital gluten and HPMC (Hydroxypropyl methyl cellulose) for pasta processing quality characteristics such as pasta dough rheology, microstructure, cooking quality, and sensory evaluation. Rheological studies showed maximum dough stability in Comb1 (T. aestivum wheat flour and semolina). Colour and cooking quality of Comb2 (T. durum semolina and T. aestivum wheat flour) and Comb3 (T. aestivum wheat semolina and T. durum semolina) were comparable with control. Pasting results indicated that T. aestivum semolina gave the lowest onset gelatinization temperature (66.9 degrees C) but the highest peak viscosity (1.053 BU). Starch release was maximum in Comb1 (53.45%) when compared with control (44.9%) as also proved by microstructure studies. Firmness was seen to be slightly high in Comb3 (2.430 N) when compared with control (2.304 N), and sensory evaluations were also in the acceptable range for the same. The present study concludes that Comb3 comprising 50% T. durum semolina and 50% T. aestivum refined wheat flour with additives would be optimal alternate for 100% T. durum semolina for production of financially viable pasta. PMID- 26904602 TI - Retrogradation of Waxy Rice Starch Gel in the Vicinity of the Glass Transition Temperature. AB - The retrogradation rate of waxy rice starch gel was investigated during storage at temperatures in the vicinity of the glass transition temperature of a maximally concentrated system (T g '), as it was hypothesized that such temperatures might cause different effects on retrogradation. The T g ' value of fully gelatinized waxy rice starch gel with 50% water content and the enthalpy of melting retrograded amylopectin in the gels were investigated using differential scanning calorimetry. Starch gels were frozen to -30 degrees C and stored at 4, 0, -3, -5, and -8 degrees C for 5 days. The results indicated that the T g ' value of gelatinized starch gel annealed at -7 degrees C for 15 min was -3.5 degrees C. Waxy rice starch gels retrograded significantly when stored at 4 degrees C with a decrease in the enthalpy of melting retrograded starch in samples stored for 5 days at -3, -5, and -8 degrees C, respectively, perhaps due to the more rigid glass matrix and less molecular mobility facilitating starch chain recrystallization at temperatures below T g '. This suggests that retardation of retrogradation of waxy rice starch gel can be achieved at temperature below T g '. PMID- 26904603 TI - Development of Low-Fat Soft Dough Biscuits Using Carbohydrate-Based Fat Replacers. AB - Experiments were conducted to develop low-fat soft dough biscuits using carbohydrate-based fat replacers (maltodextrin and guar gum). A central composite rotatable design was used to optimise the level of sugar 24-36%, composite fat (fat 10.5-24.5%, maltodextrin 10.4-24%, and guar gum 0.1-0.5%), ammonium bicarbonate 0.5-2.5%, and water 20-24% for production of low-fat biscuits. Diameter (P < 0.01) and stress-strain ratio (P < 0.05) decreased significantly with increase in the amount of sugar. There was a significant decrease (P < 0.01) in spread ratio at high amount of water. Hardness was significantly affected by the interactions of ammonium bicarbonate with sugar (P < 0.05) and fat (P < 0.1). The optimum level of ingredients obtained for low-fat biscuits was sugar 31.7 g, fat 13.55 g, maltodextrin 21.15 g, guar gum 0.3 g, ammonium bicarbonate 2.21 g, and water 21 mL based on 100 g flour. The fat level in the optimised low-fat biscuit formulation was found to be 8.48% as compared to 22.65% in control; therefore, the reduction in fat was 62.5%. PMID- 26904604 TI - Survivability of Vibrio cholerae O1 in Cooked Rice, Coffee, and Tea. AB - This study aimed to investigate the survival of Vibrio cholerae O1 in 3 types of preparation for cooked rice, Oryza sativa L., (plain rice, rice with coconut milk, and rice with ginger); coffee, Coffea canephora, (plain coffee, coffee with sugar, and coffee with sweetened condensed milk); and tea, Camellia sinensis, (plain tea, tea with sugar, and tea with sweetened condensed milk) held at room temperature (27 degrees C). The survival of V. cholerae O1 was determined by spread plate method on TCBS agar. Initial cultures of 8.00 log CFU/mL were inoculated into each food sample. After 6 h incubation, significant growth was only detected in rice with coconut milk (9.67 log CFU/mL; P < 0.05). However, all 3 types of rice preparation showed significant growth of V. cholerae after 24 h (P < 0.05). For coffee and tea preparations, V. cholerae survived up to 6 h in tea with condensed milk (4.72 log CFU/mL) but not in similar preparation of coffee. This study showed evidence for the survivability of V. cholerae in rice, coffee, and tea. Thus, holding these food and beverages for an extended period of time at room temperature should be avoided. PMID- 26904605 TI - Extrusion Conditions and Amylose Content Affect Physicochemical Properties of Extrudates Obtained from Brown Rice Grains. AB - The utilization of whole grains in food formulations is nowadays recommended. Extrusion cooking allows obtaining precooked cereal products and a wide range of ready-to-eat foods. Two rice varieties having different amylose content (Fortuna 16% and Paso 144, 27%) were extruded using a Brabender single screw extruder. Factorial experimental design was used to study the effects of extrusion temperature (160, 175, and 190 degrees C) and grits moisture content (14%, 16.5%, and 19%) on extrudate properties. Specific mechanical energy consumption (SMEC), radial expansion (E), specific volume (SV), water absorption (WA), and solubility (S) were determined on each extrudate sample. In general, Fortuna variety showed higher values of SMEC and S (703-409 versus 637-407 J/g; 33.0-21.0 versus 20.1 11.0%, resp.) than those of Paso 144; on the contrary SV (8.64-3.47 versus 8.27 4.53 mL/g) and WA tended to be lower (7.7-5.1 versus 8.4-6.6 mL/g). Both varieties showed similar values of expansion rate (3.60-2.18). Physical characteristics depended on extrusion conditions and rice variety used. The degree of cooking reached by Paso rice samples was lower than that obtained for Fortuna. It is suggested that the presence of germ and bran interfered with the cooking process, decreasing friction level and broadening residence time distribution. PMID- 26904606 TI - Ethoxyquin: An Antioxidant Used in Animal Feed. AB - Ethoxyquin (EQ, 6-ethoxy-1,2-dihydro-2,2,4-trimethylquinoline) is widely used in animal feed in order to protect it against lipid peroxidation. EQ cannot be used in any food for human consumption (except spices, e.g., chili), but it can pass from feed to farmed fish, poultry, and eggs, so human beings can be exposed to this antioxidant. The manufacturer Monsanto Company (USA) performed a series of tests on ethoxyquin which showed its safety. Nevertheless, some harmful effects in animals and people occupationally exposed to it were observed in 1980's which resulted in the new studies undertaken to reevaluate its toxicity. Here, we present the characteristics of the compound and results of the research, concerning, for example, products of its metabolism and oxidation or searching for new antioxidants on the EQ backbone. PMID- 26904607 TI - Bioactivity of Nonedible Parts of Punica granatum L.: A Potential Source of Functional Ingredients. AB - Punica granatum L. has a long standing culinary and medicinal traditional use in Mauritius. This prompted a comparative study to determine the bioefficacy of the flower, peel, leaf, stem, and seed extracts of the Mauritian P. granatum. The flower and peel extracts resulting from organic solvent extraction exhibited strong antioxidant activities which correlated with the high levels of total phenolics, flavonoids, and proanthocyanidins. The peel extract had the most potent scavenging capacity reflected by high Trolox equivalent antioxidant capacity value (5206.01 +/- 578.48 MUmol/g air dry weight), very low IC50 values for hypochlorous acid (0.004 +/- 0.001 mg air dry weight/mL), and hydroxyl radicals scavenging (0.111 +/- 0.001 mg air dry weight/mL). Peel extracts also significantly inhibited S. mutans (P < 0.001), S. mitis (P < 0.001), and L. acidophilus (P < 0.05) growth compared to ciprofloxacin. The flower extract exhibited high ferric reducing, nitric oxide scavenging, and iron (II) ions chelation and significantly inhibited microsomal lipid peroxidation. Furthermore, it showed a dose-dependent inhibition of xanthine oxidase with an IC50 value of 0.058 +/- 0.011 mg air dry weight/mL. This study showed that nonedible parts of cultivated pomegranates, that are generally discarded, are bioactive in multiassay systems thereby suggesting their potential use as natural prophylactics and in food applications. PMID- 26904608 TI - Effect of Extraction Conditions on the Antioxidant Activity of Olive Wood Extracts. AB - An investigation to optimize the extraction yield and the radical scavenging activity from the agricultural by-product olive tree wood (Olea europaea L., cultivar Picual) using six different extraction protocols was carried out. Four olive wood samples from different geographical origin, and harvesting time have been used for comparison purposes. Among the fifty olive wood extracts obtained in this study, the most active ones were those prepared with ethyl acetate, either through direct extraction or by successive liquid-liquid partitioning procedures, the main components being the secoiridoids oleuropein and ligustroside. An acid hydrolysis pretreatment of olive wood samples before extractions did not improve the results. In the course of this study, two compounds were isolated from the ethanolic extracts of olive wood collected during the olives' harvesting season and identified as (7''R)-7'' ethoxyoleuropein (1) and (7''S)-7''-ethoxyoleuropein (2). PMID- 26904609 TI - Microbiological Safety Assessment of Fermented Cassava Flour "Lafun" Available in Ogun and Oyo States of Nigeria. AB - The microorganisms involved in the fermentation and spoilage of fermented cassava flour were investigated. The water samples used at the different processing sites were also investigated to determine their safety status. There was predominance of Staphylococcus aureus, Aspergillus spp., and Escherichia coli in all samples. Coliforms were observed to be present in all of the processing water. In the fermented cassava flour, the total bacterial count ranged between 4.9 * 10(6) cfu/mL from Eleso, Bakatari, and Oja Odan processing sites and 8.10 * 10(6) cfu/mL in Eruku processing site. The majority of the microorganisms involved in the spoilage of "lafun" were found to be Aspergillus niger which ranged between 4.6 * 10(5) cfu/mL in Eleso and 8.1 * 10(5) cfu/mL in Kila. The control sample prepared in the laboratory had a low microbial load compared to samples collected from various sites and markets. PMID- 26904611 TI - UHPLC/MS-MS Analysis of Six Neonicotinoids in Honey by Modified QuEChERS: Method Development, Validation, and Uncertainty Measurement. AB - Rapid and reliable multiresidue analytical methods were developed and validated for the determination of 6 neonicotinoids pesticides (acetamiprid, clothianidin, imidacloprid, nitenpyram, thiacloprid, and thiamethoxam) in honey. A modified QuEChERS method has allowed a very rapid and efficient single-step extraction, while the detection was performed by UHPLC/MS-MS. The recovery studies were carried out by spiking the samples at two concentration levels (10 and 40 MUg/kg). The methods were subjected to a thorough validation procedure. The mean recovery was in the range of 75 to 114% with repeatability below 20%. The limits of detection were below 2.5 MUg/kg, while the limits of quantification did not exceed 4.0 MUg/kg. The total uncertainty was evaluated taking the main independent uncertainty sources under consideration. The expanded uncertainty did not exceed 49% for the 10 MUg/kg concentration level and was in the range of 16 19% for the 40 MUg/kg fortification level. PMID- 26904610 TI - Mineral Properties and Dietary Value of Raw and Processed Stinging Nettle (Urtica dioica L.). AB - Stinging nettle (Urtica dioica L.) has a long history of usage and is currently receiving attention as a source of fiber and alternative medicine. In many cultures, nettle is also eaten as a leafy vegetable. In this study, we focused on nettle yield (edible portion) and processing effects on nutritive and dietary properties. Actively growing shoots were harvested from field plots and leaves separated from stems. Leaf portions (200 g) were washed and processed by blanching (1 min at 96-98 degrees C) or cooking (7 min at 98-99 degrees C) with or without salt (5 g.L(-1)). Samples were cooled immediately after cooking and kept in frozen storage before analysis. Proximate composition, mineral, amino acid, and vitamin contents were determined, and nutritive value was estimated based on 100 g serving portions in a 2000 calorie diet. Results show that processed nettle can supply 90%-100% of vitamin A (including vitamin A as beta carotene) and is a good source of dietary calcium, iron, and protein. We recommend fresh or processed nettle as a high-protein, low-calorie source of essential nutrients, minerals, and vitamins particularly in vegetarian, diabetic, or other specialized diets. PMID- 26904612 TI - Effect of Maltodextrins on the Rheological Properties of Potato Starch Pastes and Gels. AB - The study examines the effects of maltodextrins saccharified to various degrees on some rheological properties of potato starch dispersions. Pasting characteristics, flow curves, and mechanical spectra were determined for native potato starch and for its blends with potato maltodextrins having dextrose equivalents (DE) of 10.5, 18.4, and 26.5. The results showed that medium saccharified maltodextrin (DE = 18.4) gave the strongest effect, manifesting itself as a considerable reduction in the viscosity at pasting, a decrease in apparent viscosity during flow, and a decrease in the storage and loss moduli. Addition of high-(DE = 26.5) or low-(DE = 10.5) saccharified maltodextrins had a markedly smaller effect on the rheological properties of starch. The differences in the effects produced by the maltodextrins are closely connected to the degree of polymerisation of the maltooligosaccharides in the systems. PMID- 26904613 TI - Grape Seed Procyanidin Extract Improves Insulin Production but Enhances Bax Protein Expression in Cafeteria-Treated Male Rats. AB - In a previous study, the administration of a grape seed procyanidin extract (GSPE) in female Wistar rats improved insulin resistance, reduced insulin production, and modulated apoptosis biomarkers in the pancreas. Considering that pharmacokinetic and pharmacodynamic parameters in females are different from these parameters in males, the aim of the present study was to evaluate the effects of GSPE on male Wistar cafeteria-induced obese rats. The results have confirmed that the cafeteria model is a robust model mimicking a prediabetic state, as these rats display insulin resistance, increased insulin synthesis and secretion, and increased apoptosis in the pancreas. In addition, GSPE treatment (25 mg/kg of GSPE for 21 days) in male rats improves insulin resistance and counteracts the cafeteria-induced effects on insulin synthesis. However, the administration of the extract enhances the cafeteria-induced increase in Bax protein levels, suggesting increased apoptosis. This result contradicts previous results from cafeteria-fed female rats, in which GSPE seemed to counteract the increased apoptosis induced by the cafeteria diet. PMID- 26904615 TI - Microwave Heating as an Alternative Quarantine Method for Disinfestation of Stored Food Grains. AB - Insects and pests constitute a major threat to food supplies all over the world. Some estimates put the loss of food grains because of infestation to about 40% of the world production. Contemporary disinfestation methods are chemical fumigation, ionizing radiation, controlled atmosphere, conventional hot air treatment, and dielectric heating, that is, radio frequency and microwave energy, and so forth. Though chemical fumigation is being used extensively in stored food grains, regulatory issues, insect resistance, and environmental concerns demand technically effective and environmentally sound quarantine methods. Recent studies have indicated that microwave treatment is a potential means of replacing other techniques because of selective heating, pollution free environment, equivalent or better quality retention, energy minimization, and so forth. The current paper reviews the recent advances in Microwave (MW) disinfestation of stored food products and its principle and experimental results from previous studies in order to establish the usefulness of this technology. PMID- 26904614 TI - Peanut Allergy, Allergen Composition, and Methods of Reducing Allergenicity: A Review. AB - Peanut allergy affects 1-2% of the world's population. It is dangerous, and usually lifelong, and it greatly decreases the life quality of peanut-allergic individuals and their families. In a word, peanut allergy has become a major health concern worldwide. Thirteen peanut allergens are identified, and they are briefly introduced in this paper. Although there is no feasible solution to peanut allergy at present, many methods have shown great promise. This paper reviews methods of reducing peanut allergenicity, including physical methods (heat and pressure, PUV), chemical methods (tannic acid and magnetic beads), and biological methods (conventional breeding, irradiation breeding, genetic engineering, enzymatic treatment, and fermentation). PMID- 26904616 TI - Changes in Acidity, TSS, and Sugar Content at Different Storage Periods of the Postharvest Mango (Mangifera indica L.) Influenced by Bavistin DF. AB - A detailed study was carried out with the postharvest mangoes (namely, the Langra and the Khirshapat) treated with different levels of Bavistin DF (BDF) solution (namely, 250, 500, and 750 ppm) for obtaining results on biochemical changes as well as storability of postharvest mango. The experiment was laid out in randomized complete block design with three replicates. The results of the experiments exhibited that only the single effect of varieties was found to be significant in most of the parameters studied. The Langra enriched a greater quantity of titratable acidity and total soluble solid (TSS) at 3rd day, over the Khirshapat. On the other hand, Khirshapat showed increased pulp pH and TSS at all the storage duration. The results explored that some physicochemical properties, namely, pulp pH, TSS, sugar (total, reducing, and nonreducing), and titratable acidity along with shelf life drastically decreased from untreated mangoes. Bavistin DF with the doses of 750 ppm showed better results in delaying the changes in physicochemical properties and extended shelf life. PMID- 26904617 TI - Determining Food Insecurity: An Application of the Rasch Model with Household Survey Data in Uganda. AB - The inexplicable nature of food insecurity in parts of Uganda and worldwide necessitated an investigation into the nature, extent, and differentials of household food security. The main objective of this study was to examine the food security dynamics and model household food insecurity. The Rasch modelling approach was employed on a dataset from a sample of 1175 (Tororo = 577; Busia = 598) randomly selected households in the year 2010. All households provided responses to the food security questions and none was omitted from the analysis. At 5 percent level of significance the analysis indicated that Tororo district average food security assessment (0.137 +/- 0.181) was lower than that for Busia district (0.768 +/- 0.177). All the mean square fit statistics were in the range of 0.5 to 1.5, and none of them showed any signs of distortion, degradation, or less productivity for measurement. This confirmed that items used in this study were very productive for measurement of food security in the study area. The study recommends further analysis where item responses are ordered polytomous rather than the dichotomous item response functions used. Furthermore, consideration should be given to fit models that allow for different latent distributions for households with children and those without children and possibly other subgroups of respondents. PMID- 26904618 TI - Fruit Leathers: Method of Preparation and Effect of Different Conditions on Qualities. AB - Fruit leathers are dehydrated fruit products which are eaten as snacks or desserts. They are flexible sheets that have a concentrated fruit flavor and nutritional aspects. Most fruit leathers are prepared by mixing fruit puree and other additives like sugar, pectin, acid, glucose syrup, color, and potassium metabisulphite and then dehydrating them under specific conditions. Various drying systems including combined convective and far-infrared drying, hot air drying, microwave drying, solar drying, and sun drying have been used to make fruit leathers. Most fruit leathers are dried at 30 to 80 degrees C for up to 24 hours until the target final moisture content (12-20%) has been reached. Research about fruit leathers began in the 1970s. This work has reviewed published papers on fruit leathers in order to summarize useful information about fruit leathers on methods of preparation, effects of drying condition, and effects of packaging and storage, which will be useful to many in the food industry and consumers who are health-conscious. PMID- 26904619 TI - Effect of Hydroxypropylation on Functional Properties of Different Cultivars of Sweet Potato Starch in Sri Lanka. AB - Starches obtained from different cultivars of sweet potatoes commonly consumed in Sri Lanka, were chemically modified with hydroxypropyl substitution, to analyze the changes in the physicochemical properties. Significant changes (P < 0.05) in the crude digestibility level, thermal properties, and the water separation (syneresis) of starch gels (7.0% db) during cold and frozen storage were observed due to the modification. Hydroxypropylation increased the gel stability, water solubility, digestibility, and storage stability of the native starches in the cold storage to a significant level. Lowered gelatinization and retrogradation enthalpies as well as gelatinization temperature were observed for derivatized starches compared to the native starch. Low levels of pasting stability with increased levels of breakdown and reduced cold paste viscosity were observed in the hydroxypropylated starch samples except for the Malaysian cultivar (S5). Chemically modified starch gels stored under cold storage did not show a syneresis for two weeks in the cycle and the frozen storage showed much improved stability in the starch gels within the four-week cycle. Chemical modification of sweet potato starch with hydroxyl propyl substitution can enhance the functional characteristics of the native starch which will improve its potential application in the food industry. PMID- 26904620 TI - A Novel Vision Sensing System for Tomato Quality Detection. AB - Producing tomato is a daunting task as the crop of tomato is exposed to attacks from various microorganisms. The symptoms of the attacks are usually changed in color, bacterial spots, special kind of specks, and sunken areas with concentric rings having different colors on the tomato outer surface. This paper addresses a vision sensing based system for tomato quality inspection. A novel approach has been developed for tomato fruit detection and disease detection. Developed system consists of USB based camera module having 12.0 megapixel interfaced with ARM-9 processor. Zigbee module has been interfaced with developed system for wireless transmission from host system to PC based server for further processing. Algorithm development consists of three major steps, preprocessing steps like noise rejection, segmentation and scaling, classification and recognition, and automatic disease detection and classification. Tomato samples have been collected from local market and data acquisition has been performed for data base preparation and various processing steps. Developed system can detect as well as classify the various diseases in tomato samples. Various pattern recognition and soft computing techniques have been implemented for data analysis as well as different parameters prediction like shelf life of the tomato, quality index based on disease detection and classification, freshness detection, maturity index detection, and different suggestions for detected diseases. Results are validated with aroma sensing technique using commercial Alpha Mos 3000 system. Accuracy has been calculated from extracted results, which is around 92%. PMID- 26904621 TI - Moisture Sorption Behaviour and Mould Ecology of Trade Garri Sold in South Eastern Nigeria. AB - Garri is a creamy white or yellow starchy grit produced by roasting to gelatinization and dryness of peeled, washed, mashed, and fermented dewatered cassava roots. It is the most important product of cassava in West and Central Africa. Mean moisture content of yellow and white garri was 11.11% and 10.81% within 24 hrs of sampling from the market, increasing to 17.27% and 16.14%, respectively, following 3 months of storage at room temperature. The water activity of samples varied from initial 0.587 to 0.934 following storage. Moisture sorption isotherms, determined by static gravimetric techniques at 20 degrees and 30 degrees C, showed temperature dependent BET Sigmoidal type II behaviour typical of carbohydrate rich foods but modulated very slightly by the content of palm oil. Equilibrium moisture content decreased with increase in temperature at constant water activity. A total of 10 fungal species belonging to the genera Mucor, Penicillium, Cephalosporium, Aspergillus, Scopulariopsis, Rhizopus, and Paecilomyces were identified, with range increasing with water activity of samples. PMID- 26904622 TI - Chemical and Functional Properties of Chia Seed (Salvia hispanica L.) Gum. AB - Chia (Salvia hispanica L.) constitutes a potential alternative raw material and ingredient in food industry applications due to its dietary fiber content. Gum can be extracted from its dietary fiber fractions for use as an additive to control viscosity, stability, texture, and consistency in food systems. The gum extracted from chia seeds was characterized to determine their quality and potential as functional food additives. The extracted chia gum contained 26.2% fat and a portion was submitted to fat extraction, producing two fractions: gum with fat (FCG) and gum partly defatted (PDCG). Proximal composition and physicochemical characterization showed these fractions to be different (P < 0.05). The PDCG had higher protein, ash, and carbohydrates content than the FCG, in addition to higher water-holding (110.5 g water/g fiber) and water-binding capacities (0.84 g water/g fiber). The FCG had greater oil-holding capacity (25.7 g oil/g fiber) and water absorption capacity (44 g water/g fiber). In dispersion trials, the gums exhibited a non-Newtonian fluid behavior, specifically shear thinning or pseudoplastic type. PDCG had more viscosity than FCG. Chia seed is an excellent natural source of gum with good physicochemical and functional qualities, and is very promising for use in food industry. PMID- 26904623 TI - HPLC-Profiles of Tocopherols, Sugars, and Organic Acids in Three Medicinal Plants Consumed as Infusions. AB - Pterospartum tridentatum (L.) Willk, Gomphrena globosa L., and Cymbopogon citratus (DC.) Stapf are medicinal plants that require a more detailed chemical characterization, given the importance of their consumption as infusions. Therefore, the individual profiles in tocopherols, free sugars, and organic acids were obtained by high performance liquid chromatography (HPLC) coupled to different detectors (fluorescence, refraction index, and photodiode array, resp.). C. citratus revealed the highest content of alpha-, and total tocopherols, glucose, sucrose, succinic, and ascorbic acids. P. tridentatum presented the highest fructose and total sugars content. Otherwise, G. globosa showed the highest organic acids concentration. As far as we know, this is the first study reporting the mentioned chemical compounds in G. globosa and C. citratus. PMID- 26904625 TI - Fatty Acid Composition and Lipid Profile of Diospyros mespiliformis, Albizia lebbeck, and Caesalpinia pulcherrima Seed Oils from Nigeria. AB - The screening of lesser-known underutilized seeds as source of food has been a way of finding solution to food insecurity in developing nations. In this regard, oil as a class of food was extracted from the seeds of Diospyros mespiliformis (4.72 +/- 0.2%), Albizia lebbeck (6.40 +/- 0.60%), and Caesalpinia pulcherrima (7.2 +/- 0.30%). The oils were finally analyzed for their fatty acid composition, lipid classes, fatty acid distribution in the lipid fractions, and molecular speciation of the triacylglycerols, glycolipids, and phospholipids. The fatty acid composition of the oils varied with C18:2 fatty acid being the most dominant in the oils. Neutral lipids were the most abundant lipid class found in the oils while molecular species of the triacylglycerol with equivalent carbon chain number C40 was majorly present in the oils of Diospyros mespiliformis and Caesalpinia pulcherrima. The present study presents lesser-known underutilized seeds as possible sources of food. PMID- 26904624 TI - Antiglycation Activity of Iridoids and Their Food Sources. AB - Iridoids are dietary phytochemicals that may have the ability to inhibit the formation of advanced glycation end products (AGEs). Three studies were conducted to investigate this anti-AGE potential. First, the inhibition of fluorescence intensity by food-derived iridoids, after 4 days of incubation with bovine serum albumin, glucose, and fructose, was used to evaluate in vitro antiglycation activity. Next, an 8-week open-label pilot study used the AGE Reader to measure changes in the skin autofluorescence of 34 overweight adults who consumed daily a beverage containing food sources of iridoids. Finally, a cross-sectional population study with 3913 people analyzed the relationship between daily iridoid intake and AGE accumulation, as measured by skin autofluorescence with the TruAge scanner. In the in vitro test, deacetylasperulosidic acid and loganic acid both inhibited glycation in a concentration-dependent manner, with respective IC50 values of 3.55 and 2.69 mM. In the pilot study, average skin autofluorescence measurements decreased by 0.12 units (P < 0.05). The cross-sectional population survey revealed that, for every mg of iridoids consumed, there is a corresponding decline in AGE associated age of 0.017 years (P < 0.0001). These results suggest that consumption of dietary sources of iridoids may be a useful antiaging strategy. PMID- 26904626 TI - Physicochemical and Phytochemical Analyses of Copra and Oil of Cocos nucifera L. (West Coast Tall Variety). AB - Coconut copra from West coast tall variety, cultivated in Kerala, India, was subjected to aqueous and solvent extractions (using n-hexane). Additionally, oil was extracted from the copra in Soxhlet assembly using petroleum ether (b.p. 60 80 degrees C). Physicochemical and phytochemical analyses were conducted for the extracts and the oil, with commercial coconut oil as the experimental control. The physicochemical analyses showed that the aqueous extract of copra was milky white in color with a sweet odor, while the solvent extract was pale yellow and odorless. The commercial oil had 0.08 +/- 0.02% oleic acid and a TOTOX value of 7.73 +/- 0.78, lower than the Soxhlet extracted oil. Among all the extracts and oils, best phytochemical properties, antioxidant activity (DPPH activity, IC50 value 0.04 +/- 0.01 mg/mL), total phenol (0.96 +/- 0.04 mg gallic acid eq./g dry copra), reducing power (40.49 +/- 1.84 mg BHT eq./g dry copra), and anti inflammatory activity (NO activity, IC50 value 0.77 +/- 0.06 mg/mL) were obtained in the commercial coconut oil, followed by the Soxhlet extracted oil, aqueous extract, and solvent extract. Fatty acid composition analyses showed mainly medium chain fatty acids in the copra oil with lauric acid as the predominant fatty acid (51.88% and 44.84% in Soxhlet extracted and commercial oils, resp.). PMID- 26904627 TI - Cooking Chicken Breast Reduces Dialyzable Iron Resulting from Digestion of Muscle Proteins. AB - The purpose of this research was to study the effect of cooking chicken breast on the production of dialyzable iron (an in vitro indicator of bioavailable iron) from added ferric iron. Chicken breast muscle was cooked by boiling, baking, sauteing, or deep-frying. Cooked samples were mixed with ferric iron and either extracted with acid or digested with pepsin and pancreatin. Total and ferrous dialyzable iron was measured after extraction or digestion and compared to raw chicken samples. For uncooked samples, dialyzable iron was significantly enhanced after both extraction and digestion. All cooking methods led to markedly reduced levels of dialyzable iron both by extraction and digestion. In most cooked, digested samples dialyzable iron was no greater than the iron-only (no sample) control. Cooked samples showed lower levels of histidine and sulfhydryls but protein digestibility was not reduced, except for the sauteed sample. The results showed that, after cooking, little if any dialyzable iron results from digestion of muscle proteins. Our research indicates that, in cooked chicken, residual acid extractable components are the most important source of dialyzable iron. PMID- 26904628 TI - Microbes Associated with Freshly Prepared Juices of Citrus and Carrots. AB - Fruit juices are popular drinks as they contain antioxidants, vitamins, and minerals that are essential for human being and play important role in the prevention of heart diseases, cancer, and diabetes. They contain essential nutrients which support the growth of acid tolerant bacteria, yeasts, and moulds. In the present study, we have conducted a microbiological examination of freshly prepared juices (sweet lime, orange, and carrot) by serial dilution agar plate technique. A total of 30 juice samples were examined for their microbiological quality. Twenty-five microbial species including 9 bacterial isolates, 5 yeast isolates, and 11 mould isolates were isolated from juices. Yeasts and moulds were the main cause of spoilage of juices. Aspergillus flavus and Rhodotorula mucilaginosa were observed in the maximum number of juice samples. Among bacteria Bacillus cereus and Serratia were dominant. Escherichia coli and Staphylococcus aureus were detected in few samples. Candida sp., Curvularia, Colletotrichum, and Acetobacter were observed only in citrus juice samples. Alternaria, Aspergillus terreus, A. niger, Cladosporium, and Fusarium were also observed in tested juice samples. Some of the microorganisms detected in these juice samples can cause disease in human beings, so there is need for some guidelines that can improve the quality of fruit juices. PMID- 26904629 TI - Spray Drying of Rhodomyrtus tomentosa (Ait.) Hassk. Flavonoids Extract: Optimization and Physicochemical, Morphological, and Antioxidant Properties. AB - The optimal condition of spray drying purified flavonoids extract from R. tomentosa berries was studied by response surface methodology. The optimized condition for microencapsulation was of maltodextrin to gum Arabic ratio 1 : 1.3, total solid content 27.4%, glycerol monostearate content 0.25%, and core to coating material ratio 3 : 7, resulting in EE 91.75%. Prepared at the optimized condition, the flavonoids extract microcapsules (FEMs) were irregularly spherical particles with low moisture content (3.27%), high solubility (92.35%), and high bulk density (0.346 g/cm(3)). DPPH radical scavenging activity of FEMs was not decreased after spray drying (P > 0.05) and higher than those in citric acid and rutin at the same concentration. Moreover, FEMs effectively retarded the oxidation of fresh lard during the 10-day storage period compared with vitamin C, nonencapsulated flavonoids extract, and rutin. Therefore, FEMs produced at the optimized condition could be used as powder ingredients with antioxidant capacities. PMID- 26904630 TI - Arsenic Species in Edible Seaweeds Using In Vitro Biomimetic Digestion Determined by High-Performance Liquid Chromatography Inductively Coupled Plasma Mass Spectrometry. AB - Arsenite [As (III)], arsenate [As (V)], methylarsonate (MMA), and dimethylarsinate (DMA) in five edible seaweeds (the brown algae Laminaria japonica, red algae Porphyra yezoensis, brown algae Undaria pinnatifida, brown algae Hizikia fusiformis, and green algae Enteromorpha prolifera) were analyzed using in vitro digestion method determined by high-performance liquid chromatography inductively coupled plasma mass spectrometry. The results showed that DMA was found in the water extracts of all samples; As (III) were detected in L. japonica and U. pinnatifida and about 23.0 and 0.15 mg/kg of As (V) were found in H. fusiformis and E. prolifera respectively. However, after the gastrointestinal digestion, As (V) was not detected in any of the five seaweeds. About 0.19 and 1.47 mg/kg of As (III) was detected in the gastric extracts of L. japonica and H. fusiformis, respectively, and about 0.31 and 0.10 mg/kg of As (III) were extracted from the intestinal extracts of Porphyra yezoensis and U. pinnatifida, respectively. The present results successfully reveal the differences of As species and levels in the water and biomimetic extracts of five edible seaweeds. The risk assessment of the inorganic arsenic in the five edible seaweeds based on present data showed almost no hazards to human health. PMID- 26904631 TI - Determination of Trace Metals and Essential Minerals in Selected Fruit Juices in Minna, Nigeria. AB - Levels of trace metals and essential minerals in selected fruit juice samples purchased from Minna were determined using atomic absorption spectrophotometer (AAS) and Flame photometer. From the obtained result, Cu, Fe, Mn, Na, and Zn were present in all the samples, while Cd, Pb, and Cr were not detectable in all the samples. Concentrations of K range between 1.31 +/- 0.10 and 41.20 +/- 0.10 mg/100 mL, Na between 15.47 +/- 0.15 and 3.50 +/- 0.20 mg/100 mL, Mn between Nd and 0.27 +/- 0.08 mg/100 mL, Fe between Nd and 0.90 +/- 0.05 mg/100 mL, Cu between Nd-0.60 +/- 0.00 mg/100 mL, and Zn between Nd-0.09 +/- 0.01 mg/100 mL, respectively. The trace metal levels in all the samples were within permissible limit as recommended by WHO for edible foods and drinks and could therefore be taken to compliment the deficiency of these essential minerals from other food sources. PMID- 26904632 TI - A Study on the Quality and Identity of Brazilian Pampa Biome Honey: Evidences for Its Beneficial Effects against Oxidative Stress and Hyperglycemia. AB - We characterized, for the first time, the quality and identity of Brazilian Pampa biome honey and its antioxidant properties in vitro (FRAP, DDPH and ABTS). The potential protective effect of honey against oxidative stress induced by iron (Fe) and paraquat, (PQ) in a Drosophila melanogaster model (in vivo) was also tested. The results indicated that all honey samples tested showed antioxidant activity in vitro. Flies treated with honey showed increased lifespan and were protected against oxidative stress induced by Fe and PQ. Despite the high concentration of sugars in honey (approximately 70-80%), our results demonstrate a hypoglycemic-like effect of honey in Drosophila. Thus, this study demonstrates the high quality of Brazilian Pampa biome honey as well as its significant antioxidant activity in vitro and in vivo, pointing to the potential use of this natural product as an alternative in the therapy of oxidative stress-associated diseases. PMID- 26904633 TI - Physicochemical Properties of Flaxseed Fortified Extruded Bean Snack. AB - Milled flaxseed was incorporated (0-20%) into a combination of bean-corn flours and extruded in a twin screw extruder using corn curl method. Physicochemical parameters such as water activity, color, expansion ratio, bulk density, lipid content, and peroxide values of extruded snack were analyzed. Scanning electron micrographs were taken. Peroxide values and propanal contents were measured over four months of storage. Rancidity scores of extruded snack were measured using a trained panel. As expected, omega-3 fatty acids and bulk density increased with increasing flaxseed fortification levels. Extrudates with more flaxseed had decreased lightness values and expansion ratios. However, only the 15 and 20% flaxseed containing extrudates had expansion ratios that were significantly (P <= 0.05) different from the control. In general, no significant difference (P > 0.05) in water activity values was observed in the flaxseed fortified extrudates, except in the navy-corn based extrudates. Peroxide values increased with increased flaxseed levels and over a storage period. However, propanal values did not change significantly in the 5-10% flaxseed fortified extrudates but increased in extrudates with higher levels of flaxseed. Rancidity scores were correlated with peroxide values and did not increase significantly during storage under nitrogen flushed conditions. PMID- 26904634 TI - Effect of Hydrocolloids and Emulsifiers on Baking Quality of Composite Cassava Maize-Wheat Breads. AB - Cassava is widely available worldwide but bread quality is impaired when cassava is used in the bread formulation. To overcome this problem, different improvers were tested in the preparation of composite cassava-maize-wheat (CMW) breads. Emulsifiers, diacetyl tartic acid ester of monoglycerides (DATEM), sodium stearoyl-2-lactylate (SSL), and lecithin (LC); and hydrocolloids, carboxymethylcellulose (CMC) and high-methylated pectin (HM pectin) were added during dough preparation of the composite flours (cassava-maize-wheat, 40 : 10 : 50). Each emulsifier was tested in combination with the hydrocolloids at levels of 0.1, 0.3, and 0.5% while hydrocolloids were used at a level of 3%. Bread quality attributes such as specific loaf volume, crust colour, crumb moisture, and firmness were measured. The specific volume of the fresh breads significantly improved with the addition of hydrocolloids (7.5 and 13%) and in combination with emulsifiers (from 7.9 to 27%) compared with bread produced without improvers. A significant improvement of brownness index and firmness of the composite flours breads was achieved with the addition of hydrocolloids and emulsifiers. The results show that emulsifiers and hydrocolloids can significantly improve the baking quality of CMW breads and thereby enhance the potential for using locally produced flours in bread baking. PMID- 26904635 TI - Food Safety Challenges towards Safe, Healthy, and Nutritious Street Foods in Bangladesh. AB - The street foods play an important socioeconomic role in meeting food and nutritional requirements of city consumers at affordable prices to the lower and middle income people. The number of food poisoning notifications rose steadily worldwide since the inception of E. coli O157:H7 outbreak in the 1980s to date. This may be partly attributed to improved surveillance, increased global trade and travel, changes in modern food production, the impact of modern lifestyles, changes in food consumption, and the emergence of new pathogens. Consumer's knowledge and attitude may influence food safety behavior and practice. For the sake of public health, it is important to understand the epidemiology of foodborne illnesses that help in prevention and control efforts, appropriately allocating resources to control foodborne illness, monitoring and evaluation of food safety measures, development of new food safety standards, and assessment of the cost-effectiveness of interventions. This review paper described the sociodemographic characteristics, common hazards, and occupational hazards of street food vendors, microbial risk associated with street food, food safety interventions and control measures, regulatory aspects and legal requirements, financial constraints, and attitudes. PMID- 26904636 TI - Rheological Characterization of Isabgol Husk, Gum Katira Hydrocolloids, and Their Blends. AB - The rheological parameters of Isabgol husk, gum katira, and their blends were determined in different media such as distilled water, 0.1 N HCl, and phosphate buffer (pH 7.4). The blend properties of Isabgol husk and gum katira were measured for four different percentage compositions in order to understand their compatibility in dispersion form such as 00 : 100, 25 : 50, 50 : 50, 75 : 25, and 100 : 00 in the gel strength of 1 mass%. The miscibility of blends was determined by calculating Isabgol husk-gum katira interaction parameters by Krigbaum and Wall equation. Other rheological properties were analyzed by Bingham, Power, Casson, Casson chocolate, and IPC paste analysis. The study revealed that the power flow index "p" was less than "1" in all concentrations of Isabgol husk, gum katira, and their blends dispersions indicating the shear-thinning (pseudoplastic) behavior. All blends followed pseudoplastic behavior at thermal conditions as 298.15, 313.15, and 333.15 degrees K and in dispersion media such as distilled water, 0.1 N HCl, and phosphate buffer (pH 7.4). Moreover, the study indicated the applicability of these blends in the development of drug delivery systems and in industries, for example, ice-cream, paste, nutraceutical, and so forth. PMID- 26904638 TI - Cashew Nut Quality as Influenced by Microwave Heating Used for Stored Grain Insect Control. AB - The objective of this work is to investigate the effect of microwave power levels (240, 360, and 480 W) and exposure time (30, 60, 90, 120, 180, and 240 s) on various properties of cashew nuts being used for disinfestation. The nuts were analyzed for moisture content, temperature rise, colour, free fatty acid (FFA) and peroxide value (PV). Experiments were conducted according to the response surface methodology. Increase in microwave power level and exposure time caused a decrease in moisture content, increase in temperature, and change in colour. Microwave treatment to target temperatures of 50-55 degrees C (unfavorable for insect survival) made the PV of cashew nut decrease to 1.10 to 1.66 meq O2/Kg (from an initial value of 2.08 +/- 0.05) and FFA value to 0.11 to 0.51% (from an initial value of 0.68 +/- 0.03). Though PV and FFA values of microwave treated cashew nut were found to increase after 6 months of storage at room conditions, the values were within the limits for acceptable quality. Microwave treated cashew nuts were free from infestation and rancidity even after 6 months of storage while the untreated nuts were found to be heavily infested at the end of 1 month of storage. PMID- 26904637 TI - Influence of Commercial Saturated Monoglyceride, Mono-/Diglycerides Mixtures, Vegetable Oil, Stirring Speed, and Temperature on the Physical Properties of Organogels. AB - The objective of this study was to evaluate the influence of gelator, vegetable oil, stirring speed, and temperature on the physical properties of obtained organogels. They were prepared under varying independent conditions and applying a fractional experimental design. From there a rheological characterization was developed. The physical characterization also included polarized light microscopy and calorimetric analysis. Once these data were obtained, X-Ray diffraction was applied to selected samples and a microstructure lattice was confirmed. Commonly, the only conditions that affect crystallization have been analyzed (temperature, solvent, gelator, and cooling rate). We found that stirring speed is the most important parameter in the organogel preparation. PMID- 26904639 TI - Effect of Acacia Gum, NaCl, and Sucrose on Physical Properties of Lotus Stem Starch. AB - Consumer preferences in east Asian part of the world pave the way for consumption of lotus stem starch (LSS) in preparations such as breakfast meals, fast foods, and traditional confectioneries. The present study envisaged the investigation and optimization of additives, that is, acacia gum, sodium chloride (NaCl), and sucrose, on water absorption (WA), water absorption index (WAI), and water solubility index (WSI) of LSS employing response surface methodology (RSM). Acacia gum resulted in increased water uptake and swelling of starch; however, NaCl reduced the swelling power of starch by making water unavailable to starch and also due to starch-ion electrostatic interaction. Sucrose restricted the water absorption by binding free water and decreased amylose leaching by building bridges with starch chains and thus forming rigid structure. PMID- 26904640 TI - Water Extractable Phytochemicals from Peppers (Capsicum spp.) Inhibit Acetylcholinesterase and Butyrylcholinesterase Activities and Prooxidants Induced Lipid Peroxidation in Rat Brain In Vitro. AB - Background. This study sought to investigate antioxidant capacity of aqueous extracts of two pepper varieties (Capsicum annuum var. accuminatum (SM) and Capsicum chinense (RO)) and their inhibitory effect on acetylcholinesterase and butyrylcholinesterase activities. Methods. The antioxidant capacity of the peppers was evaluated by the 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radical scavenging ability and ferric reducing antioxidant property. The inhibition of prooxidant induced lipid peroxidation and cholinesterase activities in rat brain homogenates was also evaluated. Results. There was no significant difference (P > 0.05) in the total phenol contents of the unripe and ripe Capsicum spp. extracts. Ripe and unripe SM samples had significantly higher (P < 0.05) ABTS(*) scavenging ability than RO samples, while the ripe fruits had significantly higher (P < 0.05) ferric reducing properties in the varieties. Furthermore, the extracts inhibited Fe(2+) and quinolinic acid induced lipid peroxidation in rats brain homogenates in a dose-dependent manner. Ripe and unripe samples from SM had significantly higher AChE inhibitory abilities than RO samples, while there was no significant difference in the BuChE inhibitory abilities of the pepper samples. Conclusion. The antioxidant and anticholinesterase properties of Capsicum spp. may be a possible dietary means by which oxidative stress and symptomatic cognitive decline associated with neurodegenerative conditions could be alleviated. PMID- 26904641 TI - Improvement of the Quality and the Shelf Life of the High Oxygen Modified Atmosphere Packaged Veal by Superficial Spraying with Dihydroquercetin Solution. AB - The improvement of quality and the shelf life of veal by combination of 80%O2/20%CO2 modified atmosphere packaging and superficial spraying with 0.02% dihydroquercetin solutions was studied. The control samples C, air packaged only, D, air packaged sprayed by 0.02% dihydroquercetin solution, MAP, modified atmosphere packaging only, BMAP, modified atmosphere packaging sprayed by 0.02% butylated hydroxytoluene solution, and DMAP, modified atmosphere packaging sprayed by 0.02% dihydroquercetin solution, were measured. The best results were obtained in modified atmosphere packaging sprayed by 0.02% dihydroquercetin solution. Comparisons with control samples were expressed as reduction in acid value with 27.72%, peroxide value with 64.74%, 2-thiobarbituric acid reactive substances (TBARS) with 65.71%, and the pH with 6.18%. The acid and peroxide values, TBARS, and pH were decreased linearly in response when applying the combination of 80%O2/20%CO2 modified atmosphere packaging and superficial spraying with 0.02% dihydroquercetin solutions (P < 0.05). The changes of amino nitrogen content of modified atmosphere packaging veal were not influenced statistically significantly by 0.02% dihydroquercetin solution (P > 0.05). According to results obtained it was concluded that 80%O2/20%CO2 modified atmosphere packaged veal stored at 0 +/- 0.5 degrees C after 0.02% dihydroquercetin solution treatment can preserve its quality and shelf life to 15 d postmortem. PMID- 26904642 TI - Microbiological, Nutritional, and Sensory Quality of Bread Produced from Wheat and Potato Flour Blends. AB - Dehydrated uncooked potato (Irish and sweet) flour was blended by weight with commercial wheat flour at 0 to 10% levels of substitution to make bread. Comparative study of the microbial and nutritional qualities of the bread was undertaken. The total aerobic bacterial counts ranged from 3.0 * 10(5) cfu/g to 1.09 * 10(6) cfu/g while the fungal counts ranged from 8.0 * 10(1) cfu/g to 1.20 * 10(3) cfu/g of the sample. Coliforms were not detected in the bread. Bacteria isolated were species of Bacillus, Staphylococcus, and Micrococcus while fungi isolates were species of Aspergillus, Penicillium, Rhizopus, and Mucor. The mean sensory scores (color, aroma, taste, texture, and general acceptability) were evaluated. The color of the bread baked from WF/IPF2 (wheat/Irish potato flour, 95 : 5%) blend was preferred to WF (wheat flour, 100%) while WF/SPF1 (wheat/sweet potato flour, 100%) and WF/IPF1 (wheat/Irish potato flour, 90 : 10%) aroma were preferred to WF. However, the bread baked from WF, WF/IPF2 (wheat flour/Irish potato flour, 95 : 5%), and WF/SPF2 (wheat/sweet potato flour, 95 : 5%) was more acceptable than other blends. The use of hydrated potato flour in bread making is advantageous due to increased nutritional value, higher bread yield, and reduced rate of staling. PMID- 26904643 TI - Composition and Fatty Acid Profile of Goat Meat Sausages with Added Rice Bran. AB - A scientific consensus on the relationship between obesity, obesity related diseases, and diet has emerged. One of the factors is overconsumption of the red meats such as pork and beef. Goat meat has the potential to replace these traditionally consumed meats. Rice bran is a rich source of antioxidants such as vitamin E. In this study, goat meat sausages were formulated to contain 0, 1.5 or 3 percent stabilized rice bran. Proximate and fatty acid composition, alpha tocopherol, cholesterol concentration, and antioxidant activities of cooked goat meat sausages containing varying percentages of rice bran were measured. Data were analyzed using a fixed effects model. The fat percentage in the goat meat sausages increased in response to increasing rice bran percentages (P < 0.001). Saturated fatty acids concentration decreased linearly (P < 0.01), while unsaturated fatty acids and omega-3 and omega-6 fatty acids increased linearly in response to increasing rice bran percentages (P < 0.05). The concentration of alpha-tocopherol in sausages increased linearly in response to increasing rice bran percentages (P < 0.01). Also, antioxidant activity increased linearly in sausages in response to added rice bran (P < 0.01). The cholesterol concentration of sausages did not vary significantly in response to added rice bran. PMID- 26904644 TI - Quality Assessment and Physicochemical Characteristics of Bran Enriched Chapattis. AB - Cereal brans singly and in combination were blended at varying levels (5 and 10%) for development of Chapattis. Cereal bran enriched Chapattis were assessed for quality and physicochemical characteristics. On the basis of quality assessment, 10% enrichment level for Chapatti was the best. Moisture content, water activity, and free fatty acids remained stable during the study period. Quality assessment and physicochemical characteristics of bran enriched Chapattis carried out revealed that dough handling and puffing of bran enriched Chapattis prepared by 5 and 10% level of bran supplementation did not vary significantly. All types of bran enriched Chapattis except rice bran enriched Chapattis showed nonsticky behavior during dough handling. Bran enriched Chapattis exhibited full puffing character during preparation. The sensory attributes showed that both 5 and 10% bran supplemented Chapattis were acceptable. PMID- 26904645 TI - Ripening of Sudanese Braided (Muddaffara) Cheese Manufactured from Raw or Pasteurized Milk: Effect of Heat Treatment and Salt Concentration on the Physicochemical Properties. AB - The objective of the study was to investigate the interactive effect of heat treatment (raw or pasteurized milk), ripening in salted whey (SW) and storage period for up to 3 months on the physicochemical properties of Sudanese braided cheese (SBC). Braided cheeses were manufactured from raw (BCRM) and pasteurized (BCPM) milk and ripened in SW (0%, 5%, and 10% salt) for up to 90 days. All the treatments significantly (P <= 0.05) affected the physicochemical characteristics of SBC. The total solid, protein, and fat contents of BCRM or BCPM decreased (P <= 0.05), whereas their TA, SN, and salt contents increased significantly (P <= 0.05) as storage period and the salt level of the whey were elevated. Both FRI and SRI of BCRM and BCPM increased with the increase in storage period and the salt level of the whey. For SN, FRI, SRI, pH, and moisture contents the magnitude of the change was more pronounced in BCRM than in BCPM, while for protein, fat, salt, and TS contents, the opposite was true; that is, the magnitude of the change was more pronounced in BCPM than in BCRM. Further studies are required to standardize muddaffara cheese manufacturing procedure particularly in rural areas. PMID- 26904646 TI - The Use of Lactic Acid Bacteria Starter Culture in the Production of Nunu, a Spontaneously Fermented Milk Product in Ghana. AB - Nunu, a spontaneously fermented yoghurt-like product, is produced and consumed in parts of West Africa. A total of 373 predominant lactic acid bacteria (LAB) previously isolated and identified from Nunu product were assessed in vitro for their technological properties (acidification, exopolysaccharides production, lipolysis, proteolysis and antimicrobial activities). Following the determination of technological properties, Lactobacillus fermentum 22-16, Lactobacillus plantarum 8-2, Lactobacillus helveticus 22-7, and Leuconostoc mesenteroides 14-11 were used as single and combined starter cultures for Nunu fermentation. Starter culture fermented Nunu samples were assessed for amino acids profile and rate of acidification and were subsequently evaluated for consumer acceptability. For acidification properties, 82%, 59%, 34%, and 20% of strains belonging to Lactobacillus helveticus, L. plantarum, L. fermentum, and Leu. mesenteriodes, respectively, demonstrated fast acidification properties. High proteolytic activity (>100 to 150 MUg/mL) was observed for 50% Leu. mesenteroides, 40% L. fermentum, 41% L. helveticus, 27% L. plantarum, and 10% Ent. faecium species. In starter culture fermented Nunu samples, all amino acids determined were detected in Nunu fermented with single starters of L. plantarum and L. helveticus and combined starter of L. fermntum and L. helveticus. Consumer sensory analysis showed varying degrees of acceptability for Nunu fermented with the different starter cultures. PMID- 26904647 TI - Dissolution of Lipid-Based Matrices in Simulated Gastrointestinal Solutions to Evaluate Their Potential for the Encapsulation of Bioactive Ingredients for Foods. AB - The goal of the study was to compare the dissolution of chocolate to other lipid based matrices suitable for the microencapsulation of bioactive ingredients in simulated gastrointestinal solutions. Particles having approximately 750 MUm or 2.5 mm were prepared from the following lipid-based matrices: cocoa butter, fractionated palm kernel oil (FPKO), chocolate, beeswax, carnauba wax, and paraffin. They were added to solutions designed to simulate gastric secretions (GS) or duodenum secretions (DS) at 37 degrees C. Paraffin, carnauba wax, and bees wax did not dissolve in either the GS or DS media. Cocoa butter, FPKO, and chocolate dissolved in the DS medium. Cocoa butter, and to a lesser extent chocolate, also dissolved in the GS medium. With chocolate, dissolution was twice as fast as that with small particles (750 MUm) as compared to the larger (2.5 mm) ones. With 750 MUm particle sizes, 90% dissolution of chocolate beads was attained after only 60 minutes in the DS medium, while it took 120 minutes for 70% of FPKO beads to dissolve in the same conditions. The data are discussed from the perspective of controlled release in the gastrointestinal tract of encapsulated ingredients (minerals, oils, probiotic bacteria, enzymes, vitamins, and peptides) used in the development of functional foods. PMID- 26904648 TI - Effect of Vacuum Frying on Changes in Quality Attributes of Jackfruit (Artocarpus heterophyllus) Bulb Slices. AB - The effect of frying temperatures and durations on the quality of vacuum fried jackfruit (JF) chips was evaluated. Moisture content and breaking force of JF chips decreased with increase in frying temperature and time during vacuum frying whereas the oil content increased. The frying time for JF chips was found to be 30, 25, and 20 minutes at 80, 90, and 100 degrees C, respectively. JF chips fried at higher temperature resulted in maximum shrinkage (48%). The lightness in terms of hunter L (*) value decreased significantly (P < 0.05) during frying. Sensory evaluation showed maximum acceptability for JF chips fried at 90 degrees C for 25 min. Frying under vacuum at lower temperatures was found to retain bioactive compounds such as total phenolics, total flavonoids, and total carotenoids in JF chips. Almost 90% of carotenoids were lost from the samples after 30 min of frying at 100 degrees C. PMID- 26904649 TI - Rheological and Quality Characteristics of Taftoon Bread as Affected by Salep and Persian Gums. AB - Effects of salep gum at concentrations of 0.5%, 1%, 3%, and 5% (w/w flour basis) and the Persian gum at concentrations of 0.5%, 1%, and 3% (w/w flour basis) and combination of the two gums at concentrations of 0.5% + 0.5%, 0.75% + 0.25%, and 0.25% + 0.75% on rheological properties of the wheat flour dough and quality of Taftoon bread were studied with regard to retardation of staling. Rheological (farinograph and extensograph) characteristics, staling, and organoleptic evaluations were performed on the dough and the resulting Taftoon bread. Statistical results showed that the salep gum at 5% and Persian gum at 3% (w/w flour basis) had a significant effect on the dough properties. Salep and Persian gums when each separately added increased and decreased dough water absorption, respectively. Both hydrocolloids increased the dough resistance to extension and decreased its extensibility. Persian gum shows dual nature in water absorption and some other baking properties. Textural studies revealed that addition of 5% salep gum (w/w flour basis) reduced the bread crumb firmness and delayed the staling process of the Taftoon bread. X-ray diffraction study also confirmed this result. PMID- 26904650 TI - Comparative Study of Raw and Boiled Silver Pomfret Fish from Coastal Area and Retail Market in Relation to Trace Metals and Proximate Composition. AB - Trace metals concentration and proximate composition of raw and boiled silver pomfret (Pampus argenteus) from coastal area and retail market were determined to gain the knowledge of the risk and benefits associated with indiscriminate consumption of marine fishes. The effects of cooking (boiling) on trace metal and proximate composition of silver pomfret fish were also investigated. Trace element results were determined by the Energy Dispersive X-ray Fluorescence (EDXRF) Spectrometer wherein fish samples from both areas exceeded the standard limits set by FAO/WHO for manganese, lead, cadmiumm and chromium and boiling has no significant effects on these three metal concentrations. Long-term intake of these contaminated fish samples can pose a health risk to humans who consume them. PMID- 26904651 TI - Carbon Monoxide Fumigation Improved the Quality, Nutrients, and Antioxidant Activities of Postharvest Peach. AB - Peaches (Prunus persica cv. Yanhong) were fumigated with carbon monoxide (CO) at 0, 0.5, 5, 10, and 20 MUmol/L for 2 hours. The result showed that low concentration CO (0.5-10 MUmol/L) might delay the decrease of firmness and titrable acid content, restrain the increase of decay incidence, and postpone the variation of soluble solids content, but treating peaches with high concentration CO (20 MUmol/L) demonstrated adverse effects. Further research exhibited that exogenous CO could induce the phenylalnine ammonialyase activity, maintain nutrient contents such as Vitamin C, total flavonoid, and polyphenol, and enhance antioxidant activity according to reducing power and 2,2-diphenyl-1-(2,4,6 trinitrophenyl) hydrazyl radical scavenging activity. Treating peaches with appropriate concentration CO was beneficial to the quality, nutrients, and antioxidant activity of postharvest peaches during storage time. Therefore, CO fumigation might probably become a novel method to preserve postharvest peach and other fruits in the future. PMID- 26904652 TI - Quality Characteristics, Nutraceutical Profile, and Storage Stability of Aloe Gel Papaya Functional Beverage Blend. AB - Aloe vera gel, well known for its nutraceutical potential, is being explored as a functional ingredient in a wide array of health foods and drinks. Processing of exotic fruits and herbal botanicals into functional beverage is an emerging sector in food industry. The present study was undertaken to develop a spiced functional RTS beverage blend using Aloe gel (AG) and papaya. Aloe gel (30%), papaya pulp (15%), spice extract (5%), and citric acid (0.1%) were mixed in given proportion to prepare the blend with TSS of 15 degrees Brix. The product was bottled, pasteurized, and stored at room temperature. The quality characteristics and storage stability of the spiced beverage blend (SAGPB) were compared with spiced papaya RTS beverage (SPB). Periodic analysis was carried out up to five months for various physicochemical parameters, sugar profile, bioactive compounds, microbial quality, instrumental color, and sensory acceptability. The SAGPB exhibited superior quality characteristics compared to SPB both in fresh and in stored samples. The SPB was acceptable up to four months and SAGPB for five months. The results indicate that nutraceutical rich AG could be successfully utilized to develop functional fruit beverages with improved quality and shelf life. PMID- 26904653 TI - Effect of Cymbopogon martinii, Foeniculum vulgare, and Trachyspermum ammi Essential Oils on the Growth and Mycotoxins Production by Aspergillus Species. AB - This study was performed to investigate effect of essential oils on Aspergillus spore germination, growth, and mycotoxin production. In vitro antifungal and antiaflatoxigenic activities of Cymbopogon martinii, Foeniculum vulgare, and Trachyspermum ammi essential oils were carried out on toxigenic strains of Aspergillus species. Plant materials were hydrodistilled for 4-5 h in Clevenger apparatus. 0.25 MUL/mL, 0.5 MUL/mL, 1 MUL/mL, 2 MUL/mL, and 4 MUL/mL concentrations of each essential oil were prepared in 0.1% Tween 80 (V/V). T. ammi oil showed highest antifungal activity. Absolute mycelial inhibition was recorded at 1 MUL/mL by essential oils of T. ammi. The oil also showed complete inhibition of spore germination at a concentration of 2 MUL/mL. In addition, T. ammi oil showed significant antiaflatoxigenic potency by totally inhibiting toxin production from A. niger and A. flavus at 0.5 and 0.75 MUL/mL, respectively. C. martinii, F. vulgare, and T. ammi oils as antifungals were found superior over synthetic preservative. Moreover, a concentration of 5336.297 MUL/kg body weight was recorded for LC50 on mice indicating the low mammalian toxicity. In conclusion, the essential oils from T. ammi can be a potential source of safe natural food preservative for food commodities contamination by Aspergillus species. PMID- 26904654 TI - Spray Dried Extract of Phormidium valderianum as a Promising Source of Natural Antioxidant. AB - Microencapsulation of antioxidant-rich fraction obtained by supercritical carbon dioxide extraction (at 50 degrees C, 500 bar with extraction time of 90 min, and flow rate of CO2 at 2 L/min) of lyophilized biomass of Phormidium valderianum was carried out in a spray dryer using maltodextrin and gum arabic. Microencapsulation conditions that provided the best combination of phytochemical properties such as antioxidant activity, phenolic content, and reducing power with reasonable powder yield were an inlet temperature of 130 degrees C and wall material composition as maltodextrin: gum arabic = 70 : 30. Toxicological study reported that the Anatoxin-a content of this encapsulated powder was below the limit of detection of HPLC. Storage study established that encapsulation of this antioxidant-rich algal extract resulted in eight times enhancement of half-life (T 1/2) values. The release profile of microencapsulated antioxidant-rich fraction from the encapsulated powder was found to follow first order anomalous transport kinetics. Therefore, this microencapsulated algal extract with minimum toxicity is a source of natural antioxidant and could have promising use as novel dietary supplement. PMID- 26904655 TI - Rheology of Indian Honey: Effect of Temperature and Gamma Radiation. AB - Honey brands commonly available in Indian market were characterized for their rheological and thermal properties. Viscosity of all the honey samples belonging to different commercial brands was found to decrease with increase in temperature (5-40 degrees C) and their sensitivity towards temperature varied significantly as explained by calculating activation energy based on Arrhenius model and ranged from 54.0 to 89.0 kJ/mol. However, shear rate was not found to alter the viscosity of honey indicating their Newtonian character and the shear stress varied linearly with shear rate for all honey samples. Honey is known to contain pathogenic microbial spores and in our earlier study gamma radiation was found to be effective in achieving microbial decontamination of honey. The effect of gamma radiation (5-15 kGy) on rheological properties of honey was assessed, and it was found to remain unchanged upon radiation treatment. The glass transition temperatures (T g ) of these honey analyzed by differential scanning calorimetry varied from -44.1 to -54.1 degrees C and remained unchanged upon gamma radiation treatment. The results provide information about some key physical properties of commercial Indian honey. Radiation treatment which is useful for ensuring microbial safety of honey does not alter these properties. PMID- 26904656 TI - Controlling Listeria monocytogenes Scott A on Surfaces of Fully Cooked Turkey Deli Product Using Organic Acid-Containing Marinades as Postlethality Dips. AB - This study evaluated the efficacy of organic acids applied singly or in combination as postlethality dips to sliced uncured turkey deli loaves to inhibit the growth of Listeria monocytogenes (Lm) Scott A. Treatments consisted of sodium lactate (SL; 3.6%), potassium lactate (PL; 3.6%), sodium citrate (SC; 0.75%), a combination of SL and sodium diacetate (SDA; 0.25%), and a combination of SL/PL/SDA, alongside appropriate negative and positive controls. Products were inoculated with 10(4)-10(5) CFU/mL streptomycin-resistant (1500 MUg/mL) Lm Scott A prior to treatment. Products were then stored at ~4 degrees C and sampled at 0, 7, 14, 21, 28, 42, and 56 d. The SL/SDA combination applied to turkey slices extended the lag phase through 21 days of refrigerated storage. Numbers of Lm Scott A rose by 0.7 log10 CFU/g through the 56 d storage period. The application of the SL/PL/SDA treatment to turkey product surfaces extended the lag phase through 42 d, with pathogen numbers declining after 21 d. Combination organic acid dips prolonged the lag phase for 2 to 6 wk on turkey product surfaces and can be useful as antimicrobial agents for Lm control on postlethality exposed sliced deli products. PMID- 26904657 TI - Shelf Life Determination of Fresh Blueberries (Vaccinium corymbosum) Stored under Controlled Atmosphere and Ozone. AB - Fresh blueberries are commonly stored and transported by refrigeration in controlled atmospheres to protect shelf life for long periods of storage. Ozone is an antimicrobial gas that can extend shelf life and protect fruit from microbial contamination. Shelf life of fresh highbush blueberries was determined over 10-day storage in isolated cabinets at 4 degrees C or 12 degrees C under different atmosphere conditions, including air (control); 5% O2 : 15% CO2 : 80% N2 (controlled atmosphere storage (CAS)); and ozone gas (O3) 4 ppm at 4 degrees C or 2.5 ppm at 12 degrees C, at high relative humidity (90-95%). Samples were evaluated for yeast and molds growth, weight loss, and firmness. CAS and O3 did not delay or inhibit yeast and molds growth in blueberries after 10 days at both temperatures. Fruit stored at 4 degrees C showed lower weight loss values compared with 12 degrees C. Blueberries stored under O3 atmosphere showed reduced weight loss at 12 degrees C by day 10 and loss of firmness when compared to the other treatments. Low concentrations of ozone gas together with proper refrigeration temperature can help protect fresh blueberries quality during storage. PMID- 26904658 TI - Food Safety Training Is Associated with Improved Knowledge and Behaviours among Foodservice Establishments' Workers. AB - Though several studies have evaluated the association between food safety training and behavior, little has investigated different training components in association with food handlers' performance. Foodservice workers (N = 211) with at least two years' experience were willing to participate and were selected from major foodservice establishments in Ibadan, southwestern Nigeria, and completed a survey to evaluate the association between training, training area, duration, and refresher training and food safety knowledge and practices. We observed an association between training and knowledge (P = 0.000) as well as practices (P = 0.05) of food safety while different training areas contributed similarly to food handlers' knowledge (P = 0.17) and practices (P = 0.08). However, there was a significant decline in knowledge (P = 0.01) and practices (P = 0.001) with an increase in training duration. Furthermore, foodservice employees with refresher training demonstrated significantly higher knowledge (P = 0.000) and practice (P = 0.003) levels than those without, being about 45 and 14 times more likely to, respectively, improve their knowledge (OR = 45; 95% CI: 3.47-584.34) and practice (OR = 13.5; 95% CI: 2.01-90.69). Researchers should always consider varying training components before making assertions regarding effectiveness of training on foodservice workers' behaviour. PMID- 26904659 TI - Determining the Effects of High Intensity Ultrasound on the Reduction of Microbes in Milk and Orange Juice Using Response Surface Methodology. AB - This study investigated the effects of high intensity ultrasound (temperature, amplitude, and time) on the inactivation of indigenous bacteria in pasteurized milk, Bacillus atrophaeus spores inoculated into sterile milk, and Saccharomyces cerevisiae inoculated into sterile orange juice using response surface methodology. The variables investigated were sonication temperature (range from 0 to 84 degrees C), amplitude (range from 0 to 216 MUm), and time (range from 0.17 to 5 min) on the response, log microbe reduction. Data were analyzed by statistical analysis system software and three models were developed, each for bacteria, spore, and yeast reduction. Regression analysis identified sonication temperature and amplitude to be significant variables on microbe reduction. Optimization of the inactivation of microbes was found to be at 84.8 degrees C, 216 MUm amplitude, and 5.8 min. In addition, the predicted log reductions of microbes at common processing conditions (72 degrees C for 20 sec) using 216 MUm amplitude were computed. The experimental responses for bacteria, spore, and yeast reductions fell within the predicted levels, confirming the accuracy of the models. PMID- 26904660 TI - Nutritional Properties and Antinutritional Factors of Corn Paste (Kutukutu) Fermented by Different Strains of Lactic Acid Bacteria. AB - The aim of this study is to reduce antinutritional factors and to improve the nutritional properties of Kutukutu during fermentation with Lactic Acid Bacteria (LAB). For that, Kutukutu (700 g) was prepared in the laboratory and inoculated with pure cultures of LAB (10(9) CFU/mL). Then, preparation was incubated for 120 h. Every 24 h, Kutukutu were collected, dried at 45 degrees C for 24 h, and analyzed. The results showed that Lactobacillus brevis G25 increased reducing sugars content to 80.7% in Kutukutu after 96 h of fermentation. Lactobacillus fermentum N33 reduced the starch content to 73.2%, while Lactobacillus brevis G11, L. brevis G25, and Lactobacillus cellobiosus M41 rather increased the protein content to 18.9%. The bioavailability of Mg and Fe increased, respectively, to 50.5% and 70.6% in the Kutukutu fermented with L. brevis G25. L. plantarum A6 reduced the tannin content to 98.8% and L. buchneri M11 reduced the phytate content to 95.5%. The principal component analysis (PCA) shows that, for a best reduction of antinutrients factors and improvement of protein content and minerals, Kutukutu must be fermented by L. brevis G25 and L. fermentum N33, respectively. These starter cultures could be used to ameliorate nutritional proprieties of Kutukutu during the fermentation. PMID- 26904661 TI - Food Processing and Maillard Reaction Products: Effect on Human Health and Nutrition. AB - Maillard reaction produces flavour and aroma during cooking process; and it is used almost everywhere from the baking industry to our day to day life to make food tasty. It is often called nonenzymatic browning reaction since it takes place in the absence of enzyme. When foods are being processed or cooked at high temperature, chemical reaction between amino acids and reducing sugars leads to the formation of Maillard reaction products (MRPs). Depending on the way the food is being processed, both beneficial and toxic MRPs can be produced. Therefore, there is a need to understand the different types of MRPs and their positive or negative health effects. In this review we have summarized how food processing effects MRP formation in some of the very common foods. PMID- 26904662 TI - Benzene as a Chemical Hazard in Processed Foods. AB - This paper presents a literature review on benzene in foods, including toxicological aspects, occurrence, formation mechanisms, and mitigation measures and analyzes data reporting benzene levels in foods. Benzene is recognized by the IARC (International Agency for Research on Cancer) as carcinogenic to humans, and its presence in foods has been attributed to various potential sources: packaging, storage environment, contaminated drinking water, cooking processes, irradiation processes, and degradation of food preservatives such as benzoates. Since there are no specific limits for benzene levels in beverages and food in general studies have adopted references for drinking water in a range from 1-10 ppb. The presence of benzene has been reported in various food/beverage substances with soft drinks often reported in the literature. Although the analyses reported low levels of benzene in most of the samples studied, some exceeded permissible limits. The available data on dietary exposure to benzene is minimal from the viewpoint of public health. Often benzene levels were low as to be considered negligible and not a consumer health risk, but there is still a need of more studies for a better understanding of their effects on human health through the ingestion of contaminated food. PMID- 26904663 TI - Optimization of the Hydrolysis of Safflower Oil for the Production of Linoleic Acid, Used as Flavor Precursor. AB - Commercial lipases, from porcine pancreas (PPL), Candida rugosa (CRL), and Thermomyces lanuginosus (Lipozyme TL IM), were investigated in terms of their efficiency for the hydrolysis of safflower oil (SO) for the liberation of free linoleic acid (LA), used as a flavor precursor. Although PPL, under the optimized conditions, showed a high degree of hydrolysis (91.6%), its low tolerance towards higher substrate concentrations could limit its use for SO hydrolysis. In comparison to the other investigated lipases, Lipozyme TL IM required higher amount of enzyme and an additional 3 h of reaction time to achieve its maximum degree of SO hydrolysis (90.2%). On the basis of the experimental findings, CRL was selected as the most appropriate biocatalyst, with 84.1% degree of hydrolysis. The chromatographic analyses showed that the CRL-hydrolyzed SO is composed mainly of free LA. PMID- 26904664 TI - Evolution of Volatile Flavour Compounds during Fermentation of African Oil Bean (Pentaclethra macrophylla Benth) Seeds for "Ugba" Production. AB - Fermented African oil bean (Pentaclethra macrophylla Benth) seed is a successful and well studied seasoning and snack in parts of Western Africa. GC-MS analysis of fermenting seeds revealed a mixture of several volatile aroma compounds which changed with time and starter organism. During natural mixed culture process 36 volatile compounds including 12 hydrocarbons, 10 esters, 5 alcohols, 2 phenols, 2 ketones, and one each of furan, amine, acid, thiophene, and lactone were identified. When Bacillus subtilis was used in pure culture, 30 compounds comprising 10 hydrocarbons, 8 esters, 3 alcohols, 2 amines, 2 sulfur compounds, and one of each of acid, aldehyde, phenol, ketone, and furan were identified. Sample fermented with B. megaterium produced 29 aroma compounds comprising 9 hydrocarbons, 10 esters, 2 nitrogenous compounds, 2 ketones, 3 alcohols, and one of each of lactone, aldehyde, furan, and amine. Methyl esters of various long chain fatty acids may be key aroma compounds, based on consistency and persistence. Qualitative or quantitative contribution of individual compounds may only be determined following flavour threshold analysis. PMID- 26904665 TI - Thermal Oxidation Induces Lipid Peroxidation and Changes in the Physicochemical Properties and beta -Carotene Content of Arachis Oil. AB - This study sought to investigate the effect of thermal oxidation on the physicochemical properties, malondialdehyde, and beta-carotene content of arachis oil. Pure arachis oil was heated for 20 mins with a corresponding temperature of 220 degrees C. Thereafter, changes in the physicochemical properties (acid, iodine, and peroxide values) of the oil samples were determined. Subsequently, the level of lipid peroxidation was determined using change in malondialdehyde content. Then, the total carotenoid and beta-carotene contents were evaluated using spectrophotometric method and high performance liquid chromatography, respectively. The results of the study revealed a significant increase (P < 0.05) in the acid and peroxide values and malondialdehyde concentration of the heated oil when compared with the fresh arachis oil. In contrast, a significant decrease (P < 0.05) was observed in the iodine value, total carotenoid, 13-cis-, 15-cis-, trans-, and 9-cis-beta-carotene, and total beta-carotene content of the heated oil. Hence, thermal oxidation induced lipid peroxidation and caused changes in the physicochemical properties and carotenoid contents of arachis oil, thereby reducing its nutritive value and health benefit. Therefore, cooking and frying with arachis oil for a long period might not be appropriate as this might lead to a loss of significant amount of the insignificant beta-carotene in arachis oil. PMID- 26904666 TI - Effect of Temperature, Time, and Material Thickness on the Dehydration Process of Tomato. AB - This study aimed to evaluate the effects of temperature, time, and thickness of tomatoes fruits during adiabatic drying process. Dehydration, a simple and inexpensive process compared to other conservation methods, is widely used in the food industry in order to ensure a long shelf life for the product due to the low water activity. This study aimed to obtain the best processing conditions to avoid losses and keep product quality. Factorial design and surface response methodology were applied to fit predictive mathematical models. In the dehydration of tomatoes through the adiabatic process, temperature, time, and sample thickness, which greatly contribute to the physicochemical and sensory characteristics of the final product, were evaluated. The optimum drying conditions were 60 degrees C with the lowest thickness level and shorter time. PMID- 26904667 TI - Kinetics and Quality of Microwave-Assisted Drying of Mango (Mangifera indica). AB - The effect of microwave-assisted convective air-drying on the drying kinetics and quality of mango was evaluated. Both microwave power and pretreatment time were significant factors but the effect of power was more profound. Increase in microwave power and pretreatment time had a positive effect on drying time. The nonenzymatic browning index of the fresh samples increased from 0.29 to 0.60 while the ascorbic acid content decreased with increase in microwave power and time from 3.84 mg/100g to 1.67 mg/100g. The effective moisture diffusivity varied from 1.45 * 10(-9) to 2.13 * 10(-9) m(2)/s for microwave power range of 300-600 W for 2 to 4 minutes of pretreatment. The Arrhenius type power-dependent activation energy was found to be in the range of 8.58-17.48 W/mm. The fitting of commonly used drying models to the drying data showed the Midilli et al. model as the best. Microwave power of 300 W and pretreatment time of 4 minutes emerged as the optimum conditions prior to air-drying at 7 degrees C. At this ideal condition, the energy savings as a result of microwave application was approximately 30%. Therefore, microwave-assisted drying should be considered for improved heat and mass transfer processes during drying to produce dried mangoes with better quality. PMID- 26904668 TI - Heat Pump Drying of Fruits and Vegetables: Principles and Potentials for Sub Saharan Africa. AB - Heat pump technology has been used for heating, ventilation, and air-conditioning in domestic and industrial sectors in most developed countries of the world including South Africa. However, heat pump drying (HPD) of fruits and vegetables has been largely unexploited in South Africa and by extension to the sub-Saharan African region. Although studies on heat pump drying started in South Africa several years ago, not much progress has been recorded to date. Many potential users view heat pump drying technology as fragile, slow, and high capital intensive when compared with conventional dryer. This paper tried to divulge the principles and potentials of heat pump drying technology and the conditions for its optimum use. Also, various methods of quantifying performances during heat pump drying as well as the quality of the dried products are highlighted. Necessary factors for maximizing the capacity and efficiency of a heat pump dryer were identified. Finally, the erroneous view that heat pump drying is not feasible economically in sub-Saharan Africa was clarified. PMID- 26904669 TI - Evaluation of Verigene Blood Culture Test Systems for Rapid Identification of Positive Blood Cultures. AB - The performance of molecular tests using the Verigene Gram-Positive and Gram Negative Blood Culture nucleic acid tests (BC-GP and BC-GN, resp.; Naosphere, Northbrook, IL, USA) was evaluated for the identification of microorganisms detected from blood cultures. Ninety-nine blood cultures containing Gram-positive bacteria and 150 containing Gram-negative bacteria were analyzed using the BC-GP and BC-GN assays, respectively. Blood cultures were performed using the Bactec blood culture system (BD Diagnostic Systems, Franklin Lakes, NJ, USA) and conventional identification and antibiotic-susceptibility tests were performed using a MicroScan system (Siemens, West Sacramento, CA, USA). When a single strain of bacteria was isolated from the blood culture, Verigene assays correctly identified 97.9% (94/96) of Gram-positive bacteria and 93.8% (137/146) of Gram negative bacteria. Resistance genes mecA and vanA were correctly detected by the BC-GP assay, while the extended-spectrum beta-lactamase CTX-M and the carbapenemase OXA resistance gene were detected from 30 cases cultures by the BC GN assay. The BC-GP and BC-GN assays showed high agreement with conventional identification and susceptibility tests. These tests are useful for rapid identification of microorganisms and the detection of clinically important resistance genes from positive Bactec blood cultures. PMID- 26904670 TI - Predominance of Abdominal Visceral Adipose Tissue Reflects the Presence of Aortic Valve Calcification. AB - Background. Aortic valve calcification (AVC) is a common feature of aging and is related to coronary artery disease. Although abdominal visceral adipose tissue (VAT) plays fundamental roles in coronary artery disease, the relationship between abdominal VAT and AVC is not fully understood. Methods. We investigated 259 patients who underwent cardiac and abdominal computed tomography (CT). AVC was defined as calcified lesion on the aortic valve by CT. %abdominal VAT was calculated as abdominal VAT area/total adipose tissue area. Results. AVC was detected in 75 patients, and these patients showed higher %abdominal VAT (44% versus 38%, p < 0.05) compared to those without AVC. When the cutoff value of %abdominal VAT was set at 40.9%, the area under the curve to diagnose AVC was 0.626. Multivariable logistic regression analysis showed that age (OR 1.120, 95% CI 1.078-1.168, p < 0.01), diabetes (OR 2.587, 95% CI 1.323-5.130, p < 0.01), and %abdominal VAT (OR 1.032, 95% CI 1.003-1.065, p < 0.05) were independent risk factors for AVC. The net reclassification improvement value for detecting AVC was increased when %abdominal VAT was added to the model: 0.5093 (95% CI 0.2489 0.7697, p < 0.01). Conclusion. We determined that predominance of VAT is associated with AVC. PMID- 26904671 TI - Use of a Remote Eye-Tracker for the Analysis of Gaze during Treadmill Walking and Visual Stimuli Exposition. AB - The knowledge of the visual strategies adopted while walking in cognitively engaging environments is extremely valuable. Analyzing gaze when a treadmill and a virtual reality environment are used as motor rehabilitation tools is therefore critical. Being completely unobtrusive, remote eye-trackers are the most appropriate way to measure the point of gaze. Still, the point of gaze measurements are affected by experimental conditions such as head range of motion and visual stimuli. This study assesses the usability limits and measurement reliability of a remote eye-tracker during treadmill walking while visual stimuli are projected. During treadmill walking, the head remained within the remote eye tracker workspace. Generally, the quality of the point of gaze measurements declined as the distance from the remote eye-tracker increased and data loss occurred for large gaze angles. The stimulus location (a dot-target) did not influence the point of gaze accuracy, precision, and trackability during both standing and walking. Similar results were obtained when the dot-target was replaced by a static or moving 2D target and "region of interest" analysis was applied. These findings foster the feasibility of the use of a remote eye-tracker for the analysis of gaze during treadmill walking in virtual reality environments. PMID- 26904673 TI - Fluorescent Probes for Biological Imaging. PMID- 26904672 TI - Use of Modified Polysaccharide 4DryField ((r)) PH for Adhesion Prevention and Hemostasis in Gynecological Surgery: A Two-Center Observational Study by Second Look Laparoscopy. AB - Purpose. This study evaluates both scopes of 4DryField PH, certified for adhesion prevention and hemostasis, in patients undergoing surgery for various and severe gynecological disorders. Methods. This is a two-institutional study. Adhesion prevention efficacy was evaluated using video documentation of first-look laparoscopies (FLL) and second-look laparoscopies (SLL); other patient data were analyzed retrospectively. Twenty patients with various disorders were evaluated, 4 assigned to a uterus pathology, 10 to endometriosis, and 6 to an adhesion disease group. Nine patients received 4DryField primarily for hemostasis and 11 solely for adhesion prevention. Nineteen patients had SLL after 5 to 12 weeks and one after 13 months. Results. At FLL with 4DryField, immediate hemostasis could be achieved in diffuse bleeding. At SLL, effective adhesion prevention was observed in 18 of all 20 women, with only 2 revealing major adhesions. In particular, only 1 of the 6 women with adhesion disease as predominant disorder showed major adhesions at SLL. Conclusions. Modified polysaccharide 4DryField is not only effective in diffuse bleeding. In this cohort with extensive surgery for various gynecological pathologies, 4DryField showed effective adhesion prevention as confirmed at SLL, too. Its use as premixed gel is a convenient variant for treatment of large peritoneal wounds. PMID- 26904674 TI - Method Based on the beta-Lactamase PenPC Fluorescent Labeled for beta-Lactam Antibiotic Quantification in Human Plasma. AB - Recently, Wong et al. have successfully developed a fluorescent biosensor based on the PenPC beta-lactamase which changes its intrinsic fluorescence in presence of beta-lactam antibiotics (BLAs). Here, we studied systematically this correlation among the fluorescence change of the biosensor and the concentration of different BLAs aimed at developing a novel method for estimating the concentration of a wide range of BLAs. This method showed high precision and specificity and very low interference from clinically relevant samples. We were able to monitor the pharmacokinetics of meropenem in healthy volunteers as well as in an ill animal model too, indicating that the implemented method could be suitable for clinical practice. PMID- 26904675 TI - Multipurpose, Integrated 2nd Generation Biorefineries. PMID- 26904676 TI - Corneal Dendritic Cell Density Is Associated with Subbasal Nerve Plexus Features, Ocular Surface Disease Index, and Serum Vitamin D in Evaporative Dry Eye Disease. AB - Dry eye disease (DED) has evolved into a major public health concern with ocular discomfort and pain being responsible for significant morbidity associated with DED. However, the etiopathological factors contributing to ocular pain associated with DED are not well understood. The current IVCM based study investigated the association between corneal dendritic cell density (DCD), corneal subbasal nerve plexus (SBNP) features, and serum vitamin D and symptoms of evaporative dry eye (EDE). The study included age and sex matched 52 EDE patients and 43 heathy controls. A significant increase in the OSDI scores (discomfort subscale) was observed between EDE (median, 20.8) and control (median, 4.2) cohorts (P < 0.001). Similarly, an increase in DCD was observed between EDE (median, 48.1 cells/mm(2)) patients and controls (median, 5.6 cells/mm(2)) (P < 0.001). A significant decrease in SBNP features (corneal nerve fiber length, fiber density, fiber width, total branch density, nerve branch density, and fiber area) was observed in EDE patients with OSDI score >23 (P < 0.05). A positive correlation was observed between DCD and OSDI discomfort subscale (r = 0.348; P < 0.0003) and SBNP features. An inverse correlation was observed between vitamin D and OSDI scores (r = -0.332; P = 0.0095) and DCD with dendritic processes (r = -0.322; P = 0.0122). The findings implicate DCD, SBNP features, and vitamin D with EDE symptoms. PMID- 26904677 TI - Time Dependent Assessment of Morphological Changes: Leukodepleted Packed Red Blood Cells Stored in SAGM. AB - Usually packed red blood cells (pRBCs) require specific conditions in storage procedures to ensure the maximum shelf life of up to 42 days in 2-6 degrees C. However, molecular and biochemical consequences can affect the stored blood cells; these changes are collectively labeled as storage lesions. In this study, the effect of prolonged storage was assessed through investigating morphological changes and evaluating oxidative stress. Samples from leukodepleted pRBC in SAGM stored at 4 degrees C for 42 days were withdrawn aseptically on day 0, day 14, day 28, and day 42. Morphological changes were observed using scanning electron microscopy and correlated with osmotic fragility and hematocrit. Oxidative injury was studied through assessing MDA level as a marker for lipid peroxidation. Osmotic fragility test showed that extended storage time caused increase in the osmotic fragility. The hematocrit increased by 6.6% from day 0 to day 42. The last 2 weeks show alteration in the morphology with the appearance of echinocytes and spherocytes. Storage lesions and morphological alterations appeared to affect RBCs during the storage period. Further studies should be performed to develop strategies that will aid in the improvement of stored pRBC quality and efficacy. PMID- 26904679 TI - An In Vivo Confocal Microscopic Study of Corneal Nerve Morphology in Unilateral Keratoconus. AB - Purpose. To study the corneal nerve morphology and its importance in unilateral keratoconus. Materials and Methods. In this prospective cross-sectional study, 33 eyes of 33 patients with keratoconus in one eye (Group 3) were compared with the other normal eye of the same patients (Group 2) and 30 eyes of healthy patients (Group 1). All patients underwent detailed ophthalmic examination followed by topography with Pentacam HR and in vivo confocal microscopy (IVCM). Five images obtained with IVCM were analyzed using an automated CCmetrics software version 1.0 for changes in subbasal plexus of nerves. Results. Intergroup comparison showed statistically significant reduction in corneal nerve fiber density (CNFD) and length (CNFL) in Group 3 as compared to Group 1 (p < 0.001 and p = 0.001, resp.) and Group 2 (p = 0.01 and p = 0.02, resp.). Though corneal nerve fiber length, diameter, area, width, corneal nerve branch density, and corneal total branch density were found to be higher in decentered cones, only the corneal nerve branch density (CNBD) was found to be statistically significant (p < 0.01) as compared to centered cones. Conclusion. Quantitative changes in the corneal nerve morphology can be used as an imaging marker for the early diagnosis of keratoconus before the onset of refractive or topography changes. PMID- 26904680 TI - Electrophysiological and Behavioral Responses of Theocolax elegans (Westwood) (Hymenoptera: Pteromalidae) to Cereal Grain Volatiles. AB - Volatiles emitted by the host's food would be the first signals used by parasitoids in the host location process and are thought to play an important role in host habitat location. In this study, the olfactory responses of Theocolax elegans (Westwood), a Pteromalid wasp that parasitizes immature stages of stored-product insect pests developing inside cereal or leguminous grains, to volatiles emitted by healthy wheat grains, their hexane extracts, and different doses of three individual compounds previously identified in cereal grain odors were investigated in Y-tube olfactometer and Petri dish arena behavioral bioassays and electroantennogram recordings. In Y-tube olfactometer bioassays, odors from healthy wheat grains and their hexane extracts were attractive to both sexes of T. elegans. Moreover, hexane extracts elicited arresting effects in Petri dish arena. The three synthetic compounds valeraldehyde, maltol, and vanillin elicited dose-dependent responses in both male and female adult wasps confirming the capability of the peripheral olfactory systems to perceive cereal volatiles. In behavioral bioassays, different doses of vanillin were significantly attractive to both sexes. PMID- 26904681 TI - Treatment of Copper Contaminated Municipal Wastewater by Using UASB Reactor and Sand-Chemically Carbonized Rubber Wood Sawdust Column. AB - The performance of a laboratory scale upflow anaerobic sludge blanket (UASB) reactor and its posttreatment unit of sand-chemically carbonized rubber wood sawdust (CCRWSD) column system for the treatment of a metal contaminated municipal wastewater was investigated. Copper ion contaminated municipal wastewater was introduced to a laboratory scale UASB reactor and the effluent from UASB reactor was then followed by treatment with sand-CCRWSD column system. The laboratory scale UASB reactor and column system were observed for a period of 121 days. After the posttreatment column the average removal of monitoring parameters such as copper ion concentration (91.37%), biochemical oxygen demand (BODT) (93.98%), chemical oxygen demand (COD) (95.59%), total suspended solid (TSS) (95.98%), ammonia (80.68%), nitrite (79.71%), nitrate (71.16%), phosphorous (44.77%), total coliform (TC) (99.9%), and fecal coliform (FC) (99.9%) was measured. The characterization of the chemically carbonized rubber wood sawdust was done by scanning electron microscope (SEM), X-ray fluorescence spectrum (XRF), and Fourier transforms infrared spectroscopy (FTIR). Overall the system was found to be an efficient and economical process for the treatment of copper contaminated municipal wastewater. PMID- 26904678 TI - Diagnostic Methods of Helicobacter pylori Infection for Epidemiological Studies: Critical Importance of Indirect Test Validation. AB - Among the methods developed to detect H. pylori infection, determining the gold standard remains debatable, especially for epidemiological studies. Due to the decreasing sensitivity of direct diagnostic tests (histopathology and/or immunohistochemistry [IHC], rapid urease test [RUT], and culture), several indirect tests, including antibody-based tests (serology and urine test), urea breath test (UBT), and stool antigen test (SAT) have been developed to diagnose H. pylori infection. Among the indirect tests, UBT and SAT became the best methods to determine active infection. While antibody-based tests, especially serology, are widely available and relatively sensitive, their specificity is low. Guidelines indicated that no single test can be considered as the gold standard for the diagnosis of H. pylori infection and that one should consider the method's advantages and disadvantages. Based on four epidemiological studies, culture and RUT present a sensitivity of 74.2-90.8% and 83.3-86.9% and a specificity of 97.7-98.8% and 95.1-97.2%, respectively, when using IHC as a gold standard. The sensitivity of serology is quite high, but that of the urine test was lower compared with that of the other methods. Thus, indirect test validation is important although some commercial kits propose universal cut-off values. PMID- 26904682 TI - Automated Cell Selection Using Support Vector Machine for Application to Spectral Nanocytology. AB - Partial wave spectroscopy (PWS) enables quantification of the statistical properties of cell structures at the nanoscale, which has been used to identify patients harboring premalignant tumors by interrogating easily accessible sites distant from location of the lesion. Due to its high sensitivity, cells that are well preserved need to be selected from the smear images for further analysis. To date, such cell selection has been done manually. This is time-consuming, is labor-intensive, is vulnerable to bias, and has considerable inter- and intraoperator variability. In this study, we developed a classification scheme to identify and remove the corrupted cells or debris that are of no diagnostic value from raw smear images. The slide of smear sample is digitized by acquiring and stitching low-magnification transmission. Objects are then extracted from these images through segmentation algorithms. A training-set is created by manually classifying objects as suitable or unsuitable. A feature-set is created by quantifying a large number of features for each object. The training-set and feature-set are used to train a selection algorithm using Support Vector Machine (SVM) classifiers. We show that the selection algorithm achieves an error rate of 93% with a sensitivity of 95%. PMID- 26904683 TI - Clinical Application of Antimicrobial Bone Graft Substitute in Osteomyelitis Treatment: A Systematic Review of Different Bone Graft Substitutes Available in Clinical Treatment of Osteomyelitis. AB - Osteomyelitis is a common occurrence in orthopaedic surgery, which is caused by different bacteria. Treatment of osteomyelitis patients aims to eradicate infection by debridement surgery and local and systemic antibiotic therapy. Local treatment increases success rates and can be performed with different antimicrobial bone graft substitutes. This review is performed to assess the level of evidence of synthetic bone graft substitutes in osteomyelitis treatment. According to the PRISMA statement for reporting systematic reviews, different types of clinical studies concerning treatment of osteomyelitis with bone graft substitutes are included. These studies are assessed on their methodological quality as level of evidence and bias and their clinical outcomes as eradication of infection. In the fifteen included studies, the levels of evidence were weak and in ten out of the fifteen studies there was a moderate to high risk of bias. However, first results of the eradication of infection in these studies showed promising results with their relatively high success rates and low complication rates. Due to the low levels of evidence and high risks of bias of the included studies, these results are inconclusive and no conclusions regarding the performed clinical studies of osteomyelitis treatment with antimicrobial bone graft substitutes can be drawn. PMID- 26904684 TI - Activity of Proteolytic Enzymes and Level of Cystatin C in the Peripartum Period. AB - Objectives. The aim of the study was to evaluate the activity of cathepsin B, collagenases, trypsin, and plasmin and concentration of cystatin C in serum of healthy pregnant women in peripartum period. Study Design. The study group included 45 women in uncomplicated pregnancies. Blood samples were collected in four time points. Enzyme activity was measured by spectrofluorometric method. The level of cystatin C was measured using immunonephelometric method. Results. Mean activity of cathepsin B and the level of serum cystatin C were significantly higher in the study group. Collagenase activity was significantly lower in the study group than the control group. No differences in collagenase, plasmin, and trypsin activity on each day of the peripartum period were found. Conclusion. High activity of cathepsin B and increased level of cystatin C are typical for women in late pregnancy. Those levels significantly decrease after delivery which can be associated with potential role of those markers in placental separation. The insignificant changes of cystatin C level in the peripartum period seem to exclude the possibility of using cystatin C as a marker for renal insufficiency in the peripartum period but additional research is necessary to investigate the matter further. PMID- 26904685 TI - Expressing Status and Correlation of ARID1A and Histone H2B on Breast Cancer. AB - ARID1A is one of the important cancer-related genes and regulates transcription of certain genes by altering chromatin structure. Inactivated mutations and decreased expression of ARID1A gene have been reported in several kinds of cancer. Histone H2B is a major component of chromatin and encoded by HIST1H2BE. The goal of the study is to evaluate expressing status of ARID1A and H2B as well as their correlation on breast cancer. Gene expression profiles of ARID1A and H2B on Oncomine database are analyzed. Tissue microarray of breast cancer was used for examination of ARID1A and H2B expression by immunohistochemistry. As a result, the disagreement of ARID1A expression was found, while HIST1H2BE expression is elevated in 4 out of 5 datasets on Oncomine database. There were 15 cases (20%) of breast cancers that were positive for ARID1A. Fifty-eight out of 75 cases of breast cancer (77.3%) were highly expressed for H2B protein and 17 cases (22.7%) were low expressed for H2B protein. All cases with ARID1A expression are overlapped with H2B high expression. Among 15 cases with ARID1A and H2B coexpression, 13 are invasive ductal carcinoma and 2 are mucinous carcinoma. Our results indicate that ARID1A gene may be involved in carcinogenesis of some subtypes of breast cancer. PMID- 26904686 TI - Assessment of Serum Concentrations of Ghrelin, Obestatin, Omentin-1, and Apelin in Children with Type 1 Diabetes. AB - The increasing knowledge on the functions of gastric peptides and adipokines in the body allows the assumption of their major role linking the process of food intake, nutritional status, and body growth, largely through the regulation of glucose metabolism and insulin resistance. The aim of the study was the assessment of serum levels of selected gastric peptides and adipocytokines in children with type 1 diabetes, with respect to the disease duration. The study involved 80 children aged 4-18 years (M/F -37/43). Children with type 1 diabetes (n = 46) were compared to the control group (n = 34). The study group was divided into 4 subgroups: (I) patients with newly diagnosed type 1 diabetes, after an episode of ketoacidosis (n = 10), (II) patients with type 1 diabetes of duration no longer than 5 years (n = 9), (III) patients with 5 to 10 years of DT1 (n = 20), and (IV) patients with type 1 diabetes of duration longer than 10 years (n = 7). The concentrations of gastric peptide and adipocytokines across all subgroups were lower than in the control group. The differences were statistically significant (p < 0.0001), which may be of importance in the development of the disease complications. PMID- 26904687 TI - Metformin Synergistically Enhances Cisplatin-Induced Cytotoxicity in Esophageal Squamous Cancer Cells under Glucose-Deprivation Conditions. AB - Previous studies suggest that metformin may exert a protective effect on cisplatin-induced cytotoxicity in cancer cells, and this finding has led to a caution for considering metformin use in the treatment of cancer patients. However, in this paper we provide the first demonstration that metformin synergistically augments cisplatin cytotoxicity in the esophageal squamous cancer cell line, ECA109, under glucose-deprivation conditions, which may be more representative of the microenvironment within solid tumors; this effect is very different from the previously reported cytoprotective effect of metformin against cisplatin in commonly used high glucose incubation medium. The potential mechanisms underlying the synergistic effect of metformin on cisplatin-induced cytotoxicity under glucose-deprivation conditions may include enhancement of metformin-associated cytotoxicity, marked reduction in the cellular ATP levels, deregulation of the AKT and AMPK signaling pathways, and impaired DNA repair function. PMID- 26904688 TI - Circulating Endocannabinoids and Insulin Resistance in Patients with Obstructive Sleep Apnea. AB - Objectives. The purpose of this study is to investigate the relationship between plasma endocannabinoids and insulin resistance (IR) in patients with obstructive sleep apnea (OSA). Methods. A population of 64 with OSA and 24 control subjects was recruited. Body mass index (BMI), waist circumference, lipids, blood glucose and insulin, homeostasis model of assessment for insulin resistance index (HOMA IR), anandamide (AEA), 1/2-arachidonoylglycerol (1/2-AG), and apnea-hypopnea index (AHI) were analyzed. Results. Fasting blood insulin (22.9 +/- 7.8 mIU/L versus 18.5 +/- 7.2 mIU/L, P < 0.05), HOMA-IR (2.9 +/- 1.0 versus 2.4 +/- 0.9, P < 0.01), AEA (3.2 +/- 0.7 nmol/L versus 2.5 +/- 0.6 nmol/L, P < 0.01), and 1/2-AG (40.8 +/- 5.7 nmol/L versus 34.3 +/- 7.7 nmol/L, P < 0.01) were higher in OSA group than those in control group. In OSA group, AEA, 1/2-AG, and HOMA-IR increase with the OSA severity. The correlation analysis showed significant positive correlation between HOMA-IR and AHI (r = 0.44, P < 0.01), AEA and AHI (r = 0.52, P < 0.01), AEA and HOMA-IR (r = 0.62, P < 0.01), and 1/2-AG and HOMA-IR (r = 0.33, P < 0.01). Further analysis showed that only AEA was significantly correlated with AHI and HOMA-IR after adjusting for confounding factors. Conclusions. The present study indicated that plasma endocannabinoids levels, especially AEA, were associated with IR and AHI in patients with OSA. PMID- 26904689 TI - Association between Self-Reported Habitual Snoring and Diabetes Mellitus: A Systemic Review and Meta-Analysis. AB - AIM: Several studies have reported an association between self-reported habitual snoring and diabetes mellitus (DM); however, the results are inconsistent. METHODS: Electronic databases including PubMed and EMBASE were searched. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association between snoring and DM using a random-effects model. Heterogeneity, subgroup, and sensitivity analyses were also evaluated. Begg's, Egger's tests and funnel plots were used to evaluate publication bias. RESULTS: A total of eight studies (six cross sectional and two prospective cohort studies) pooling 101,246 participants were included. Of the six cross sectional studies, the summary OR and 95% CI of DM in individuals that snore compared with nonsnorers were 1.37 (95% CI: 1.20-1.57, p < 0.001). There was no heterogeneity across the included studies (I (2) = 2.9%, p = 0.408). When stratified by gender, the pooled OR (95% CI) was 1.59 (1.20-2.11) in females (n = 12298), and 0.89 (0.65-1.22) in males (n = 4276). Of the two prospective studies, the pooled RR was 1.65 (95% CI, 1.30-2.08). CONCLUSIONS: Self-reported habitual snoring is statistically associated with DM in females, but not in males. This meta-analysis indicates a need to paying attention to the effect of snoring on the occurrence of DM in females. PMID- 26904691 TI - Interactions between Diabetes and the Heart. PMID- 26904690 TI - Diabetic Retinopathy Screening Ratio Is Improved When Using a Digital, Nonmydriatic Fundus Camera Onsite in a Diabetes Outpatient Clinic. AB - OBJECTIVE: To evaluate the effect of onsite screening with a nonmydriatic, digital fundus camera for diabetic retinopathy (DR) at a diabetes outpatient clinic. RESEARCH DESIGN AND METHODS: This cross-sectional study included 502 patients, 112 with type 1 and 390 with type 2 diabetes. Patients attended screenings for microvascular complications, including diabetic nephropathy (DN), diabetic polyneuropathy (DP), and DR. Single-field retinal imaging with a digital, nonmydriatic fundus camera was used to assess DR. Prevalence and incidence of microvascular complications were analyzed and the ratio of newly diagnosed to preexisting complications for all entities was calculated in order to differentiate natural progress from missed DRs. RESULTS: For both types of diabetes, prevalence of DR was 25.0% (n = 126) and incidence 6.4% (n = 32) (T1DM versus T2DM: prevalence: 35.7% versus 22.1%, incidence 5.4% versus 6.7%). 25.4% of all DRs were newly diagnosed. Furthermore, the ratio of newly diagnosed to preexisting DR was higher than those for DN (p = 0.12) and DP (p = 0.03) representing at least 13 patients with missed DR. CONCLUSIONS: The results indicate that implementing nonmydriatic, digital fundus imaging in a diabetes outpatient clinic can contribute to improved early diagnosis of diabetic retinopathy. PMID- 26904692 TI - Genetic Risk Score Modelling for Disease Progression in New-Onset Type 1 Diabetes Patients: Increased Genetic Load of Islet-Expressed and Cytokine-Regulated Candidate Genes Predicts Poorer Glycemic Control. AB - Genome-wide association studies (GWAS) have identified over 40 type 1 diabetes risk loci. The clinical impact of these loci on beta-cell function during disease progression is unknown. We aimed at testing whether a genetic risk score could predict glycemic control and residual beta-cell function in type 1 diabetes (T1D). As gene expression may represent an intermediate phenotype between genetic variation and disease, we hypothesized that genes within T1D loci which are expressed in islets and transcriptionally regulated by proinflammatory cytokines would be the best predictors of disease progression. Two-thirds of 46 GWAS candidate genes examined were expressed in human islets, and 11 of these significantly changed expression levels following exposure to proinflammatory cytokines (IL-1beta + IFNgamma + TNFalpha) for 48 h. Using the GWAS single nucleotide polymorphisms (SNPs) from each locus, we constructed a genetic risk score based on the cumulative number of risk alleles carried in children with newly diagnosed T1D. With each additional risk allele carried, HbA1c levels increased significantly within first year after diagnosis. Network and gene ontology (GO) analyses revealed that several of the 11 candidate genes have overlapping biological functions and interact in a common network. Our results may help predict disease progression in newly diagnosed children with T1D which can be exploited for optimizing treatment. PMID- 26904693 TI - Neutrophil-Mediated Regulation of Innate and Adaptive Immunity: The Role of Myeloperoxidase. AB - Neutrophils are no longer seen as leukocytes with a sole function of being the essential first responders in the removal of pathogens at sites of infection. Being armed with numerous pro- and anti-inflammatory mediators, these phagocytes can also contribute to the development of various autoimmune diseases and can positively or negatively regulate the generation of adaptive immune responses. In this review, we will discuss how myeloperoxidase, the most abundant neutrophil granule protein, plays a key role in the various functions of neutrophils in innate and adaptive immunity. PMID- 26904694 TI - Dendritic Cells and Leishmania Infection: Adding Layers of Complexity to a Complex Disease. AB - Leishmaniasis is a group of neglected diseases whose clinical manifestations depend on factors from the host and the pathogen. It is an important public health problem worldwide caused by the protozoan parasite from the Leishmania genus. Cutaneous Leishmaniasis (CL) is the most frequent form of this disease transmitted by the bite of an infected sandfly into the host skin. The parasites can be uptook and/or recognized by macrophages, neutrophils, and/or dendritic cells (DCs). Initially, DCs were described to play a protective role in activating the immune response against Leishmania parasites. However, several reports showed a dichotomic role of DCs in modulating the host immune response to susceptibility or resistance in CL. In this review, we discuss (1) the interactions between DCs and parasites from different species of Leishmania and (2) the crosstalk of DCs and other cells during CL infection. The complexity of these interactions profoundly affects the adaptive immune response and, consequently, the disease outcome, especially from Leishmania species of the New World. PMID- 26904697 TI - Association of Sicca Syndrome with Proviral Load and Proinflammatory Cytokines in HTLV-1 Infection. AB - The Sjogren syndrome has been diagnosed in patients with HTLV-1 associated myelopathy and dry mouth and dry eyes are documented in HTLV-1 carriers. However the diagnosis of Sjogren syndrome in these subjects has been contested. In this cross-sectional study, we evaluated the role of immunological factors and proviral load, in sicca syndrome associated with HTLV-1 in patients without myelopathy. Subjects were recruited in the HTLV-1 Clinic, from 2009 to 2011. The proviral load and cytokine levels (IFN-gamma, TNF-alpha, IL-5, and IL-10) were obtained from a database containing the values presented by the subjects at admission in the clinic. Of the 272 participants, 59 (21.7%) had sicca syndrome and in all of them anti-Sjogren syndrome related antigen A (SSA) and antigen B (SSB) were negatives. The production of TNF-alpha and IFN-gamma was higher in the group with sicca syndrome (P < 0.05) than in HTLV-1 infected subjects without sicca syndrome. Our data indicates that patients with sicca syndrome associated with HTLV-1 do not have Sjogren syndrome. However the increased production of TNF alpha and IFN-gamma in this group of patients may contribute to the pathogenesis of sicca syndrome associated with HTLV-1. PMID- 26904696 TI - Sirtuins Link Inflammation and Metabolism. AB - Sirtuins (SIRT), first discovered in yeast as NAD+ dependent epigenetic and metabolic regulators, have comparable activities in human physiology and disease. Mounting evidence supports that the seven-member mammalian sirtuin family (SIRT1 7) guard homeostasis by sensing bioenergy needs and responding by making alterations in the cell nutrients. Sirtuins play a critical role in restoring homeostasis during stress responses. Inflammation is designed to "defend and mend" against the invading organisms. Emerging evidence supports that metabolism and bioenergy reprogramming direct the sequential course of inflammation; failure of homeostasis retrieval results in many chronic and acute inflammatory diseases. Anabolic glycolysis quickly induced (compared to oxidative phosphorylation) for ROS and ATP generation is needed for immune activation to "defend" against invading microorganisms. Lipolysis/fatty acid oxidation, essential for cellular protection/hibernation and cell survival in order to "mend," leads to immune repression. Acute/chronic inflammations are linked to altered glycolysis and fatty acid oxidation, at least in part, by NAD+ dependent function of sirtuins. Therapeutically targeting sirtuins may provide a new class of inflammation and immune regulators. This review discusses how sirtuins integrate metabolism, bioenergetics, and immunity during inflammation and how sirtuin-directed treatment improves outcome in chronic inflammatory diseases and in the extreme stress response of sepsis. PMID- 26904699 TI - Spontaneous Tumor Lysis Syndrome: A Case Report and Critical Evaluation of Current Diagnostic Criteria and Optimal Treatment Regimens. AB - Tumor lysis syndrome (TLS) is a known complication of malignancy and its treatment. The incidence varies on malignancy type, but is most common with hematologic neoplasms during cytotoxic treatment. Spontaneous TLS is thought to be rare. This case study is of a 62-year-old female admitted with multisystem organ failure, with subsequent diagnosis of aggressive B cell lymphoma. On admission, laboratory abnormalities included renal failure, elevated uric acid (20.7 mg/dL), and 3+ amorphous urates on urinalysis. Oliguric renal failure persisted despite aggressive hydration and diuretic use, requiring initiation of hemodialysis prior to chemotherapy. Antihyperuricemic therapy and hemodialysis were used to resolve hyperuricemia. However, due to multisystem organ dysfunction syndrome with extremely poor prognosis, the patient ultimately expired in the setting of a terminal ventilator wean. Although our patient did not meet current TLS criteria, she required hemodialysis due to uric acid nephropathy, a complication of TLS. This poses the clinical question of whether adequate diagnostic criteria exist for spontaneous TLS and if the lack of currently accepted guidelines has resulted in the underestimation of its incidence. Allopurinol and rasburicase are commonly used for prevention and treatment of TLS. Although both drugs decrease uric acid levels, allopurinol mechanistically prevents formation of the substrate rasburicase acts to solubilize. These drugs were administered together in our patient, although no established guidelines recommend combined use. This raises the clinical question of whether combined therapy is truly beneficial or, conversely, detrimental to patient outcomes. PMID- 26904698 TI - Genetic Testing Confirmed the Early Diagnosis of X-Linked Hypophosphatemic Rickets in a 7-Month-Old Infant. AB - Loss-of-function mutations in the phosphate regulating gene with homologies to endopeptidases on the X-chromosome (PHEX) have been causally associated with X linked hypophosphatemic rickets (XLHR). The early diagnosis of XLHR in infants is challenging when it is based solely on clinical features and biochemical findings. We report a 7-month-old boy with a family history of hypophosphatemic rickets., who demonstrated early clinical evidence of rickets, although serial biochemical findings could not definitively confirm rickets. A sequencing assay targeting the PHEX gene was first performed on the mother's DNA to screen for mutations in the 5'UTR, 22 coding exons, and the exon-intron junctions. Targeted mutation analysis and mRNA studies were subsequently performed on the boys' DNA to investigate the pathogenicity of the identified mutation. Genetic screening of the PHEX gene revealed a novel mutation, c.1080-2A>C, at the splice acceptor site in intron 9. The detection of an aberrant mRNA transcript with skipped (loss of) exon 10 establishes its pathogenicity and confirms the diagnosis of XLHR in this infant. Genetic testing of the PHEX gene resulted in early diagnosis of XLHR, thus enabling initiation of therapy and prevention of progressive rachitic changes in the infant. PMID- 26904700 TI - Propylene Glycol Poisoning From Excess Whiskey Ingestion: A Case of High Osmolal Gap Metabolic Acidosis. AB - In this report, we describe a case of high anion gap metabolic acidosis with a significant osmolal gap attributed to the ingestion of liquor containing propylene glycol. Recently, several reports have characterized severe lactic acidosis occurring in the setting of iatrogenic unintentional overdosing of medications that use propylene glycol as a diluent, including lorazepam and diazepam. To date, no studies have explored potential effects of excess propylene glycol in the setting of alcohol intoxication. Our patient endorsed drinking large volumes of cinnamon flavored whiskey, which was likely Fireball Cinnamon Whisky. To our knowledge, this is the first case of propylene glycol toxicity from an intentional ingestion of liquor containing propylene glycol. PMID- 26904695 TI - Hib Vaccines: Past, Present, and Future Perspectives. AB - Haemophilus influenzae type b (Hib) causes many severe diseases, including epiglottitis, pneumonia, sepsis, and meningitis. In developed countries, the annual incidence of meningitis caused by bacteria is approximately 5-10 cases per population of 100,000. The Hib conjugate vaccine is considered protective and safe. Adjuvants, molecules that can enhance and/or regulate the fundamental immunogenicity of an antigen, comprise a wide range of diverse compounds. While earlier developments of adjuvants created effective products, there is still a need to create new generations, rationally designed based on recent discoveries in immunology, mainly in innate immunity. Many factors may play a role in the immunogenicity of Hib conjugate vaccines, such as the polysaccharides and proteins carrier used in vaccine construction, as well as the method of conjugation. A Hib conjugate vaccine has been constructed via chemical synthesis of a Hib saccharide antigen. Two models of carbohydrate-protein conjugate have been established, the single ended model (terminal amination-single method) and cross-linked lattice matrix (dual amination method). Increased knowledge in the fields of immunology, molecular biology, glycobiology, glycoimmunology, and the biology of infectious microorganisms has led to a dramatic increase in vaccine efficacy. PMID- 26904702 TI - Successful Plasma Exchange for Acute Pancreatitis Complicated With Hypertriglyceridemia: A Case Report. AB - A 33-year-old male with acute pancreatitis induced by hypertriglyceridemia had problems during treatment with plasma exchange. The hypercoagulable state was prevented by introducing innovative methods for cleaning and warming of the circuit and dialyzer. This enabled successful therapy, and the patient fully recovered from life-threatening acute pancreatitis. PMID- 26904701 TI - First-Line Use of Vemurafenib to Enable Thyroidectomy and Radioactive Iodine Ablation for BRAF-Positive Metastatic Papillary Thyroid Carcinoma: A Case Report. AB - Background. Patients with metastatic or radioactive iodine refractory papillary thyroid carcinoma (PTC) have poor prognosis due to ineffective therapy for this condition beyond surgery and radioactive iodine (RAI or (131)I). BRAF mutation occurs in more than 44% of PCT. Tyrosine kinase inhibitors, the most commonly used agents for these patients, have weak BRAF inhibition activity. BRAF inhibitors have demonstrated promising efficacy in relapsed metastatic PCT after standard treatment, though they are not currently approved for this indication. Case Presentation. We present the case of a 48-year-old Hispanic male who initially presented with columnar-cell variant subtype of PTC and positive BRAFV600E mutation. The patient had widespread bulky metastases to lungs, chest wall, brain, and bone. Discussion. Initial use of vemurafenib demonstrated a 42% cytoreduction of targeted pulmonary metastases and facilitated thyroidectomy and RAI treatment. The patient achieved a durable response over 21 months in the setting of widely metastatic disease. Conclusion. Vemurafenib may be effectively used for cytoreduction in patients with bulky metastatic PTC to bridge them to thyroidectomy and RAI treatment. PMID- 26904703 TI - Myelodysplastic Syndrome Presenting as Amegakaryocytic Thrombocytopenia in a Collodion Baby. AB - We report a rare case of myelodysplastic syndrome that presented early as amegakaryocytic thrombocytopenia in a collodion baby, which is a rare congenital disorder characterized by thick, taut membrane resembling oiled parchment or collodion, which is subsequently shed. To our knowledge, this is the first reported case of a collodion baby who presented with amegakaryocytic thrombocytopenia and who has a significant family history of the same condition. We document the rarity of this possible association and also the need for further study to establish whether a causal relationship exists. PMID- 26904704 TI - The Importance of Exclusion of Obstructive Sleep Apnea During Screening for Adrenal Adenoma and Diagnosis of Pheochromocytoma. AB - Context. As catecholamine elevation is a key element in the diagnosis of pheochromocytoma, more commonplace causes of sympathetic excess, such as obstructive sleep apnea (OSA), should be excluded as standard practice prior to diagnosis. This is essential to avoid misdiagnosis of adrenal incidentalomas identified in the estimated 42 million Americans with OSA, with greater than 4 million projected to undergo a computed tomography study annually. Case Description. A 56-year-old woman presented with a several year history of paroxysmal hypertension, palpitations, and diaphoresis. Abdominal/pelvic computed tomography performed during an unrelated hospitalization revealed a 2-cm left sided adrenal nodule initially quantified at 37 Hounsfield units. Posthospitalization, 24-hour urine normetanephrine level was markedly elevated. Reassessment 2 weeks later revealed continued normetanephrine excess. Following normal thyroid function tests, morning cortisol, aldosterone, and plasma renin activity, laparoscopic adrenalectomy was performed. Surgical pathology identified an adrenal cortical adenoma. As paroxysms continued postoperatively, repeat 24 hour urine metanephrines were measured, demonstrating essentially unchanged normetanephrine elevation. Search for an alternate cause ensued, revealing OSA with progressive continuous positive airway pressure noncompliance over the preceding year. Regular continuous positive airway pressure therapy was resumed, and at the end of 7 weeks, 24-hour urine normetanephrine levels had declined. Conclusion. Pheochromocytomas are rare and sleep apnea is common. However, the overlap of clinical symptoms between these disorders is substantial, as is their ability to produce catecholamine excess. Thus, excluding uncontrolled or undiagnosed OSA in high-risk patients should be standard practice before diagnosing pheochromocytoma. PMID- 26904706 TI - Primary Amyloidosis of Celiac/Para-Pancreatic Lymph Nodes Diagnosed by Endosonography-Guided Fine Needle Aspiration: A Case Report. AB - Introduction. Primary amyloidosis is a disorder resulting from the deposition of fibrillary protein in extracellular tissue. Diagnosis of primary amyloidosis in the celiac/para-pancreatic lymph nodes via endoscopic ultrasound-guided fine needle aspiration has not been reported in the literature. In this article, we report our first observation. Our patient is a 64-year-old Caucasian man who was referred to our institution from an outlying hospital for recurrent abdominal pain. Radiological imaging revealed an enlarged abdominal lymph node that was already biopsied under computed tomography needle guidance but diagnosis was not achieved on pathological examination. At our institution, endoscopic ultrasound guided fine needle aspiration showed enlarged para-celiac/pancreatic lymph nodes. Endosonography-guided fine needle aspiration revealed the diagnosis of primary amyloidosis. The patient tolerated the procedure well with follow-up as an outpatient. Conclusions. Lymph node involvement in amyloidosis is not uncommon. However, the involvement of the pancreatic/celiac lymph nodes by amyloidosis is obscure in this case. This case shows a rare presentation of amyloidosis diagnosed for the first time by the technique of endosonography-guided fine needle aspiration. In the future, this might serve as an establishment to standardize diagnosing abdominal lymph node amyloidosis, once suspected, by endosonography-guided fine needle aspiration. PMID- 26904705 TI - Mitochondrial Myopathy in Follow-up of a Patient With Chronic Fatigue Syndrome. AB - Introduction. Symptoms of mitochondrial diseases and chronic fatigue syndrome (CFS) frequently overlap and can easily be mistaken. Methods. We report the case of a patient diagnosed with CFS and during follow-up was finally diagnosed with mitochondrial myopathy by histochemical study of muscle biopsy, spectrophotometric analysis of the complexes of the mitochondrial respiratory chain, and genetic studies. Results. The results revealed 3% fiber-ragged blue and a severe deficiency of complexes I and IV and several mtDNA variants. Mother, sisters, and nephews showed similar symptoms, which strongly suggests a possible maternal inheritance. The patient and his family responded to treatment with high doses of riboflavin and thiamine with a remarkable and sustained fatigue and muscle symptoms improvement. Conclusions. This case illustrates that initial symptoms of mitochondrial disease in adults can easily be mistaken with CFS, and in these patients a regular reassessment and monitoring of symptoms is recommended to reconfirm or change the diagnosis. PMID- 26904707 TI - Splenic Marginal Zone Lymphoma in the Setting of Noncirrhotic Portal Hypertension. AB - We present a case of a 65-year-old Hispanic man with a history of disseminated cutaneous coccidioidomycosis who presented to the emergency room for progressively worsening abdominal pain associated with shortness of breath. The patient was found to have pleural effusion and moderate ascites on physical examination. Abdominal ultrasound and computed tomography scan were consistent with moderate ascites and portal hypertension but negative for both liver cirrhosis and for venous or arterial thrombosis. Cytology of ascitic fluid was suggestive of portal hypertension and was negative for infection. Subsequent, thoracentesis was suggestive of exudative effusion and also negative for infection. Liver biopsy confirmed the absence of cirrhosis. Complete blood count indicated pancytopenia, whereas bone marrow biopsy and flow cytometry were suggestive of marginal zone lymphoma (MZL). Clinically, the patient's shortness of breath was resolved by thoracentesis and paracentesis; however, his abdominal pain persisted. A diagnosis of idiopathic noncirrhotic portal hypertension in the setting of splenic MZL was made. The patient was transferred to a higher level of care for splenectomy; however, he missed multiple appointments. Since discharge, the patient has been seen in the outpatient setting and states that he is controlling his disease with diet and exercise; however, he continues to complain of intermittent shortness of breath with exertion. PMID- 26904708 TI - Stress Cardiomyopathy in the Setting of COPD Exacerbation. AB - Introduction. Stress cardiomyopathy, or takotsubo cardiomyopathy, is an acute, reversible left ventricular dysfunction usually initiated by a psychological or physical stress. We report this case of stress cardiomyopathy following a chronic obstructive pulmonary disease exacerbation and the subsequent treatment. Case Description. A 49-year-old white female with a history of chronic obstructive pulmonary disease presented to the emergency room via emergency medical services with worsening severe shortness of breath and productive cough for 2 weeks but denied any chest pain on arrival. On presentation, she was noted to be tachypneic, using her accessory muscles and with bilateral coarse expiratory wheezing on lung auscultation. Initial electrocardiogram demonstrated sinus tachycardia. She was treated with multiple albuterol treatments. Soon afterwards, the course was complicated by hypoxic respiratory failure eventually requiring intubation. Her repeat electrocardiogram showed acute changes consistent with myocardial infarction, and an echocardiograph demonstrated apical akinesia with an ejection fraction of 25% to 30%. The patient was urgently taken for cardiac catheterization, which showed no angiographic evidence of coronary artery disease. Three days after initial presentation, a repeat transthoracic echocardiogram showed overall left ventricular systolic function improvement. Discussion. This case provided a unique look at the difficulty of balancing catecholamines in a patient with bronchospasm and stress cardiomyopathy. PMID- 26904711 TI - Data detailing the platelet acetyl-lysine proteome. AB - Here we detail proteomics data that describe the acetyl-lysine proteome of blood platelets (Aslan et al., 2015 [1]). An affinity purification - mass spectrometry (AP-MS) approach was used to identify proteins modified by Nepsilon-lysine acetylation in quiescent, washed human platelets. The data provide insights into potential regulatory mechanisms of platelet function mediated by protein lysine acetylation. Additionally, as platelets are anucleate and lack histone proteins, they offer a unique and valuable system to study the regulation of cytosolic proteins by lysine acetylation. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (Vizcaino et al., 2014 [2]) via with PRIDE partner repository with the dataset identifier PXD002332. PMID- 26904710 TI - Treatment of hypophosphatasia by muscle-directed expression of bone-targeted alkaline phosphatase via self-complementary AAV8 vector. AB - Hypophosphatasia (HPP) is an inherited disease caused by genetic mutations in the gene encoding tissue-nonspecific alkaline phosphatase (TNALP). This results in defects in bone and tooth mineralization. We recently demonstrated that TNALP deficient (Akp2 (-/-) ) mice, which mimic the phenotype of the severe infantile form of HPP, can be treated by intravenous injection of a recombinant adeno associated virus (rAAV) expressing bone-targeted TNALP with deca-aspartates at the C-terminus (TNALP-D10) driven by the tissue-nonspecific CAG promoter. To develop a safer and more clinically applicable transduction strategy for HPP gene therapy, we constructed a self-complementary type 8 AAV (scAAV8) vector that expresses TNALP-D10 via the muscle creatine kinase (MCK) promoter (scAAV8-MCK TNALP-D10) and examined the efficacy of muscle-directed gene therapy. When scAAV8 MCK-TNALP-D10 was injected into the bilateral quadriceps of neonatal Akp2 (-/-) mice, the treated mice grew well and survived for more than 3 months, with a healthy appearance and normal locomotion. Improved bone architecture, but limited elongation of the long bone, was demonstrated on X-ray images. Micro-CT analysis showed hypomineralization and abnormal architecture of the trabecular bone in the epiphysis. These results suggest that rAAV-mediated, muscle-specific expression of TNALP-D10 represents a safe and practical option to treat the severe infantile form of HPP. PMID- 26904712 TI - Time-related trends in variability of cIMT changes in statin trials. AB - This brief article provides complementary data supporting the results reported in "Changing Characteristics of Statin-related cIMT Trials from 1988 to 2006" [1]. That article described time-related trends in baseline factors and study characteristics that may have influenced the variability of carotid intima media thickness (cIMT) endpoints (mean of mean and maximum common carotid artery [CCA]/cIMT) in published statin trials. In this brief report, additional details for the studies included in the analysis, and further supporting data, including mean of the maximum CCA/cIMT changes and subgroup data (mean and maximum CCA/cIMT) are provided. For the analysis, study-level data was extracted from 17 statin cIMT trials conducted during 1988-2006, selected on the basis of having at least one statin monotherapy arm in the absence of mixed therapy, and baseline- and study-end values for mean mean and mean maximum CCA/cIMT endpoints. The baseline mean CCA/cIMT, maximum mean CCA/cIMT and LDL-C levels, and annualized cIMT changes were estimated for the overall studies, those conducted before/after 2000, and in risk-based subgroups. Interestingly, all 8 studies conducted before 2000 were significant for cIMT change in which patients did not receive prior LLT; whereas after 2000, the results were more variable and in 4 of 6 trials that did not show a significant cIMT change, patients had received prior treatment. Baseline mean maximum cIMT and LDL-C levels, and annualized changes in studies conducted before 2000 were higher than those conducted after 2000, similar to the results reported in the original article for the mean mean cIMT endpoint. These findings were consistent across study populations of patients with CHD risk versus those without, and in studies with greater LDL-C reductions and with thickened baseline cIMT at study entry for both mean and maximum cIMT changes. Taken together, these results are consistent with trends in recent years toward greater use of lipid-lowering therapy and control of LDL-C that may have impacted the variability in the results of cIMT studies. PMID- 26904709 TI - Corneal topography in keratoconus: state of the art. AB - The morphological characterization of the cornea using corneal topographers is a widespread clinical practice that is essential for the diagnosis of keratoconus. The current state of this non-invasive exploratory technique has evolved with the possibility of achieving a great number of measuring points of both anterior and posterior corneal surfaces, which is possible due to the development of new and advanced measurement devices. All these data are later used to extract a series of topographic valuation indices that permit to offer the most exact and reliable clinical diagnosis. This paper describes the technologies in which current corneal topographers are based on, being possible to define the main morphological characteristics that the keratoconus pathology produces on corneal surface. Finally, the main valuation indices, which are provided by the corneal topographers and used for the diagnosis of keratoconus, are also defined. PMID- 26904713 TI - Characterization data of gilthead sea bream (Sparus aurata) IGF-I receptors (IGF IRa/Rb). AB - In this data article we describe the coding sequence of two IGF-IR paralogues (IGF-IRa and IGF-IRb) obtained from gilthead sea bream embryos. The putative protein architecture (domains and other important motifs) was determined and, amino acid sequences alignment and phylogenetic analysis of both receptors together with IGF-IR orthologues from different vertebrates was performed. Additionally, a semi-quantitative conventional PCR was done to analyze the mRNA expression of both receptors in different tissues of gilthead sea bream. These data will assist in further physiological studies in this species. In this sense, the expression of both receptors during ontogeny in muscle as well as the differential effects of IGF-I and IGF-II on their regulation during in vitro myogenesis has been recently studied (doi: 10.1016/j.ygcen.2015.11.011; [1]). PMID- 26904714 TI - Data supporting the regulation of FOXC2 in podocyte dysfunction. AB - This data article shows the expression levels of specific podocyte injury markers and podocyte slit diaphragm protein nephrin in obese and lean Zucker rat glomeruli. It also contains information on the effect of the overexpression of transcription factor FOXC2 on the ratio of F- and G-actin and the expression level of ZO-1 in differentiated human podocytes. The article also shows data on the effect of treatments of differentiated podocytes with various factors associated with obesity and diabetes on the expression level of FOXC2. The detailed interpretation of these data and other aspects of podocyte injury mediated by upregulation of FOXC2 can be found in "Overexpression of transcription factor FOXC2 in cultured human podocytes upregulates injury markers and increases motility [1]. PMID- 26904715 TI - The effect of repeated stress on KCC2 and NKCC1 immunoreactivity in the hippocampus of female mice. AB - K(+)-Cl(-) co-transporter (KCC2) and Na(+)-K(+)-2Cl(-) co-transporter (NKCC1) are the main regulators of neuronal intracellular chloride concentration; altered expression patterns of KCC2 and NKCC1 have been reported in several neurodegenerative diseases. In this paper, we show the effect of repeated stress on KCC2, NKCC1, and serine 940 phosphorylated KCC2 (pKCC2(ser940)) immunoreactivity. The data were obtained from the hippocampus of female mice using single-plane confocal microscopy images. The mean fluorescence intensity of the perisomatic area of neurons, defined as raw fluorescence intensity (RFI) was calculated. Repeated stress (RS) resulted in a decrease in perisomatic area of immunoreactive (IR)-KCC2 and an increase of the IR-NKCC1. In addition, RS decreased perisomatic IR-pKCC2(ser940), corresponding to that of KCC2. The data in this article support the results of a previous study [1] and provide the details of immunohistological methods. Interpretation of the data in this article can be found in "Repeated stress-induced expression pattern alterations of the hippocampal chloride transporters KCC2 and NKCC1 associated with behavioral abnormalities in female mice" by Tsukahara et al. [1]. PMID- 26904716 TI - 18S rDNA dataset profiling microeukaryotic populations within Chicago area nearshore waters. AB - Despite their critical role in the aquatic food web and nutrient cycling, microeukaryotes within freshwater environments are under-studied. Herein we present the first high-throughput molecular survey of microeukaryotes within Lake Michigan. Every two weeks from May 13 to August 5, 2014, we collected surface water samples from the nearshore waters of four Chicago area beaches: Gillson Park, Montrose Beach, 57th Street Beach, and Calumet Beach. Four biological replicates were collected for each sampling date and location, resulting in 112 samples. Eighty-nine of these samples were surveyed through targeted sequencing of the V7 and V8 regions of the 18S rDNA gene. Both technical and biological replicates were sequenced and are included in this dataset. Raw sequence data is available via NCBI's SRA database (BioProject PRJNA294919). PMID- 26904717 TI - Data on in vivo selection of SK-OV-3 Luc ovarian cancer cells and intraperitoneal tumor formation with low inoculation numbers. AB - This data paper contains information about the in vivo model for peritoneal implants used in the paper "Tumor-environment biomimetics delay peritoneal metastasis formation by deceiving and redirecting disseminated cancer cells" (De Vlieghere et al., 2015) [1]. A double in vivo selection of SK-OV-3 Luc human ovarian cancer cell line was used to create SK-OV-3 Luc IP1 and SK-OV-3 Luc IP2 cell lines. This data paper shows functional activities of the three cell lines in vitro and in vivo. Phase-contrast images show the morphology of these cells, metabolic and luciferase activity has been determined. Survival data of mice peritoneally injected with SK-OV-3 Luc or SK-OV-3 Luc IP2 is available with H&E histology of the peritoneal implants. Tumor growth curves and bioluminescent images of mice inoculated with a different number of SK-OV-3 Luc IP2 cells are also included. PMID- 26904719 TI - Facilitation as Attenuating of Environmental Stress among Structured Microbial Populations. AB - There is currently an intense debate in microbial societies on whether evolution in complex communities is driven by competition or cooperation. Since Darwin, competition for scarce food resources has been considered the main ecological interaction shaping population dynamics and community structure both in vivo and in vitro. However, facilitation may be widespread across several animal and plant species. This could also be true in microbial strains growing under environmental stress. Pure and mixed strains of Serratia marcescens and Candida rugosa were grown in mineral culture media containing phenol. Growth rates were estimated as the angular coefficients computed from linearized growth curves. Fitness index was estimated as the quotient between growth rates computed for lineages grown in isolation and in mixed cultures. The growth rates were significantly higher in associated cultures than in pure cultures and fitness index was greater than 1 for both microbial species showing that the interaction between Serratia marcescens and Candida rugosa yielded more efficient phenol utilization by both lineages. This result corroborates the hypothesis that facilitation between microbial strains can increase their fitness and performance in environmental bioremediation. PMID- 26904718 TI - Effect of High Intensity Interval and Continuous Swimming Training on Body Mass Adiposity Level and Serum Parameters in High-Fat Diet Fed Rats. AB - This study aimed to investigate the effects of interval and continuous training on the body mass gain and adiposity levels of rats fed a high-fat diet. Forty eight male Sprague-Dawley rats were randomly divided into two groups, standard diet and high-fat diet, and received their respective diets for a period of four weeks without exercise stimuli. After this period, the animals were randomly divided into six groups (n = 8): control standard diet (CS), control high-fat diet (CH), continuous training standard diet (CTS), continuous training high-fat diet (CTH), interval training standard diet (ITS), and interval training high-fat diet (ITH). The interval and continuous training consisted of a swimming exercise performed over eight weeks. CH rats had greater body mass gain, sum of adipose tissues mass, and lower serum high density lipoprotein values than CS. The trained groups showed lower values of feed intake, caloric intake, body mass gain, and adiposity levels compared with the CH group. No significant differences were observed between the trained groups (CTS versus ITS and CTH versus ITH) on body mass gains and adiposity levels. In conclusion, both training methodologies were shown to be effective in controlling body mass gain and adiposity levels in high-fat diet fed rats. PMID- 26904720 TI - Fast and Sensitive Method for Determination of Domoic Acid in Mussel Tissue. AB - Domoic acid (DA), a neurotoxic amino acid produced by diatoms, is the main cause of amnesic shellfish poisoning (ASP). In this work, we propose a very simple and fast analytical method to determine DA in mussel tissue. The method consists of two consecutive extractions and requires no purification steps, due to a reduction of the extraction of the interfering species and the application of very sensitive and selective HILIC-MS/MS method. The procedural method was validated through the estimation of trueness, extract yield, precision, detection, and quantification limits of analytical method. The sample preparation was also evaluated through qualitative and quantitative evaluations of the matrix effect. These evaluations were conducted both on the DA-free matrix spiked with known DA concentration and on the reference certified material (RCM). We developed a very selective LC-MS/MS method with a very low value of method detection limit (9 ng g(-1)) without cleanup steps. PMID- 26904721 TI - Survival and Growth of Vibrio cholerae, Escherichia coli, and Salmonella Spp. in Well Water Used for Drinking Purposes in Garoua (North Cameroon). AB - The ability of strains of faecal bacteria (Vibrio cholerae, Escherichia coli ATCC 25922, and four strains of Salmonella isolated, resp., from well water, pig, poultry, and human urine in Garoua) to survive or grow in well water microcosms was compared. Water samples were obtained from two wells in Garoua (north Cameroun). Autoclaving at 121 degrees C for 15 min and filtration through 0.2 um filter were used to make microcosms. Microcosms were constituted of unfiltered autoclaved, filtered-nonautoclaved, and filtered-autoclaved well waters. Bacterial strains were inoculated at initial cell concentration of 3 Log10CFU/mL. All strains were able to survive/grow in used microcosms, and a maximal concentration of 5.61 Log10CFU/mL was observed. Survival abilities were strain and microcosm dependent. The declines were more pronounced in filtered nonautoclaved water than in the other microcosms. E. coli and Salmonella sp. (poultry strain) lowered to undetectable levels (<1 Log10CFU/mL) after two days of water storage. V. cholera decreased over time, but surviving cells persisted for longer period in filtered-nonautoclaved water from well W1 (1.91 Log10CFU/mL) and well W2 (2.09 Log10CFU/mL). Competition for nutrients and/or thermolabile antimicrobial substances synthesized by "ultramicrocells" or by the autochthonous bacteria retained by the filter might affect the bacterial survival. PMID- 26904722 TI - Inflammatory Responses to Salmonella Infections Are Serotype-Specific. AB - The main purpose of this study was to investigate the profile of inflammatory response in patients with acute salmonellosis caused by two serotypes of Salmonella enterica, S. Enteritidis and S. Typhimurium, as well as in convalescent patients with previous acute disease caused by S. Enteritidis. Patients with acute disease showed significantly elevated levels of IL-1beta, IL 17, IL-10, and calprotectin compared to healthy control subjects. In convalescent patients, these markers were also significantly elevated, with the exception of IL-1beta. Multivariate statistical analyses with the use of these variables produced models with a good predictive accuracy resulting in excellent separation of the diseased and healthy cohorts studied. Overall, the results suggest that the profile of inflammatory response in this disease is determined, to a significant degree, by the serotype of Salmonella, and the profile of certain cytokines and calprotectin remains abnormal for a number of months following the acute disease stage. PMID- 26904723 TI - Rapid PCR Detection of Mycoplasma hominis, Ureaplasma urealyticum, and Ureaplasma parvum. AB - Objective. We compared laboratory developed real-time PCR assays for detection of Mycoplasma hominis and for detection and differentiation of Ureaplasma urealyticum and parvum to culture using genitourinary specimens submitted for M. hominis and Ureaplasma culture. Methods. 283 genitourinary specimens received in the clinical bacteriology laboratory for M. hominis and Ureaplasma species culture were evaluated. Nucleic acids were extracted using the Total Nucleic Acid Kit on the MagNA Pure 2.0. 5 MUL of the extracts were combined with 15 MUL of each of the two master mixes. Assays were performed on the LightCycler 480 II system. Culture was performed using routine methods. Results. M. hominis PCR detected 38/42 M. hominis culture-positive specimens, as well as 2 that were culture negative (sensitivity, 90.5%; specificity, 99.2%). Ureaplasma PCR detected 139/144 Ureaplasma culture-positive specimens, as well as 9 that were culture negative (sensitivity, 96.5%; specificity, 93.6%). Of the specimens that tested positive for Ureaplasma species, U. urealyticum alone was detected in 33, U. parvum alone in 109, and both in 6. Conclusion. The described PCR assays are rapid alternatives to culture for detection of M. hominis and Ureaplasma species, and, unlike culture, the Ureaplasma assay easily distinguishes U. urealyticum from parvum. PMID- 26904724 TI - New Medium for Pharmaceutical Grade Arthrospira. AB - The aim of this study is to produce a pharmaceutical grade single cell product of Arthrospira from a mixed culture. We have designed a medium derived from a combination between George's and Zarrouk's media. Our new medium has the ability to inhibit different forms of cyanobacterium and microalgae except the Chlorella. The medium and the cultivation conditions have been investigated to map the points where only Arthrospira could survive. For that, a mixed culture of pure Chlorella and Arthrospira (~90 : 10) has been used to develop the best medium composition that can lead to the enrichment of the Arthrospira growth and the inhibition of the Chlorella growth. To enable better control and to study its growth, an 80 l photobioreactor has been used. We have used high saline (2xA-St) medium which has been followed by in fermentor reducing its concentration to 1.5x. The investigation proves that Chlorella has completely disappeared. A method and a new saline medium have been established using a photobioreactor for in fermentor production of single cell Arthrospira. Such method enables the production of pure pharmaceutical grade Arthrospira for medicinal and pharmaceutical applications or as a single cell protein. PMID- 26904725 TI - Detection of Bordetella pertussis from Clinical Samples by Culture and End-Point PCR in Malaysian Patients. AB - Pertussis or whooping cough is a highly infectious respiratory disease caused by Bordetella pertussis. In vaccinating countries, infants, adolescents, and adults are relevant patients groups. A total of 707 clinical specimens were received from major hospitals in Malaysia in year 2011. These specimens were cultured on Regan-Lowe charcoal agar and subjected to end-point PCR, which amplified the repetitive insertion sequence IS481 and pertussis toxin promoter gene. Out of these specimens, 275 were positive: 4 by culture only, 6 by both end-point PCR and culture, and 265 by end-point PCR only. The majority of the positive cases were from <=3 months old patients (77.1%) (P < 0.001). There was no significant association between type of samples collected and end-point PCR results (P > 0.05). Our study showed that the end-point PCR technique was able to pick up more positive cases compared to culture method. PMID- 26904726 TI - Decreased C3 Activation by the devR Gene-Disrupted Mycobacterium tuberculosis Strain in Comparison to the Wild-Type Strain. AB - Activation of the complement component C3 is an important step in the complement cascade, contributing to inflammatory mechanisms. Considerable research on gene disrupted mycobacterial strains using animal models of tuberculosis infection has reported the roles of some of the mycobacterial genes during tuberculosis infection. The aim of the present study was to assess the pattern of complement activation by the devR gene-disrupted Mycobacterium tuberculosis H37Rv strain and compare with that by its wild-type strain. In vitro complement activation at the level of C3 by the gene-disrupted strain, its complemented strain, and wild-type strain was performed using solid-phase ELISA. It was observed that the ability of devR gene-disrupted M. tuberculosis H37Rv to activate C3 was significantly reduced in comparison to its wild-type strain (P < 0.05). In addition, C3 activation by the complemented devR mutant strain was almost similar to that of the wild strain, which indicated that the reduced ability to activate C3 could potentially be due to the deletion of devR gene. These findings indicate that the gene devR probably aids in complement activation and contributes to the inflammatory processes during tuberculosis infection. PMID- 26904727 TI - Expression, Purification, and Functional Characterization of Atypical Xenocin, Its Immunity Protein, and Their Domains from Xenorhabdus nematophila. AB - Xenorhabdus nematophila, a gram-negative bacterium belonging to the family Enterobacteriaceae is a natural symbiont of a soil nematode from the family Steinernematidae. In this study cloning, expression, and purification of broad range iron regulated multidomain bacteriocin called xenocin from X. nematophila (66 kDa, encoded by xcinA gene) and its multidomain immunity protein (42 kDa, encoded by ximB gene) have been done. xcinA-ximB (N' terminal 270 bp), translocation, and translocation-receptor domain of xcinA, ximB, and its hemolysin domain were cloned, expressed, and purified by single step Ni-NTA chromatography under native conditions. In the functional characterization, neutralization of xcinA toxicity by immunity domain of ximB gene was determined by endogenous assay. Exogenous toxic assays results showed that only the purified recombinant xenocin-immunity domain (10 kDa) protein complex had toxic activity. Atypical cognate immunity protein (42 kDa) of xenocin was fusion of immunity domain (10 kDa) and hemolysin domain (32 kDa). In silico analysis of immunity protein revealed its similarity with hemolysin and purine NTPase like proteins. Hemolytic activity was not observed in immunity protein or in its various domains; however, full-length immunity protein lacking Walker motif showed ATPase activity. Finally, using circular dichroism performed secondary structural analyses of all the recombinant proteins/protein complexes. PMID- 26904728 TI - Physiological Properties and Salmonella Growth Inhibition of Probiotic Bacillus Strains Isolated from Environmental and Poultry Sources. AB - The objective of the present study was to describe the physiological properties of seven potential probiotic strains of Bacillus spp. Isolates were characterized morphologically, biochemically, and by 16S rRNA sequence analyses for identification. Tolerance to acidic pH, high osmotic concentrations of NaCl, and bile salts were tested. Isolates were also evaluated for their ability to metabolize different carbohydrates sources. The antimicrobial sensitivity profiles were determined. Inhibition of gastrointestinal Salmonella colonization in an avian model was also evaluated. Five strains of Bacillus were tolerant to acidic conditions (pH 2.0) and all strains were tolerant to a high osmotic pressure (NaCl at 6.5%). Moreover, all strains were able to tolerate concentration of 0.037% bile salts after 24 h of incubation. Three strains were able to significantly reduce Salmonella Typhimurium levels in the crop and in the ceca of broiler-type chickens. Among the 12 antibiotics tested for antibiotic resistance, all strains were resistant to bacitracin and susceptible to gentamycin, neomycin, ormethoprim, triple sulfa, and spectinomycin. Bacterial spore formers have been shown to prevent gastrointestinal diseases in animals and humans. The results obtained in this study show important characteristics to be evaluated when selecting Bacillus spp. candidates to be used as probiotics. PMID- 26904729 TI - Mixture of Sodium Hypochlorite and Hydrogen Peroxide on Adhered Aeromonas hydrophila to Solid Substrate in Water: Impact of Concentration and Assessment of the Synergistic Effect. AB - The synergistic effects of the combined treatments of NaOCl and H2O2 on the elimination of A. hydrophila adhered to polythene under static and dynamic conditions were evaluated. The concentrations 0.1, 0.2, and 0.30/00 NaOCl and 0.5, 1, and 1.50/00 H2O2 were used. The contact periods were 180, 360, 540, and 720 minutes. The abundance of cells adhered reached 2.47 and 2.27 units (log (CFU/cm2)), respectively, under static and dynamic conditions after action of the mixture of disinfectants, whereas it reached 2.41 and 3.39 units (log (CFU/cm2)) after action of NaOCl and H2O2 alone, respectively. Increase in the incubation period resulted in a significant decrease in the abundance of cells adhered when the mixture of 0.30/00 NaOCl and 1.50/00 H2O2 was used (P < 0.01). For each cell growth phase, there was a significant difference amongst the mean densities of cells adhered after action of the mixture of disinfectants (P < 0.05). Although the Freundlich isotherm parameters relatively varied from one experimental condition to another, the K f value registered in the exponential growth phase was relatively higher in static state than in dynamic regime; cells adhered under dynamic condition seem more sensitive to the synergistic action than those adhered under static condition. PMID- 26904730 TI - Antibacterial Attributes of Apigenin, Isolated from Portulaca oleracea L. AB - The flavonoid apigenin was isolated from aerial part of P. oleracea L. The dried sample of plant was powdered and subjected to soxhlet extractor by adding 80 mL of ethanol : water (70 : 30). The extract was centrifuged at 11000 rpm for 30 min; supernatant was taken for further use. The fraction was concentrated and subjected to PTLC. The R f value of isolated apigenin was calculated (0.82). Purified material was also subjected to its IR spectra, LC-MS, NMR, and HPLC for structural elucidation. The apigenin so-obtained was subjected to antibacterial activity on five pathogenic bacterial strains like Pseudomonas aeruginosa, Salmonella typhimurium, Proteus mirabilis, Klebsiella pneumoniae and Enterobacter aerogenes; among all the bacterial strains, Salmonella typhimurium (17.36 +/- 0.18) and Proteus mirabilis (19.12 +/- 0.01) have shown maximum diameter of inhibition zone for flavonoid and remaining bacterial strains have shown moderate diameter of inhibition zone when compared with control values 14.56 +/- 0.21 and 11.68 +/- 0.13, respectively. The minimum inhibitory concentration (MIC) of the flavonoid isolated from P. oleracea L. was tested at the concentration ranging from undiluted sample to 10 mg per mL of concentration. The minimum inhibition concentration (MIC) for the flavonoid for all tested bacterial strains was found to be >4 mg per mL. Hence, the apigenin has antibacterial property and can be used to develop antibacterial drugs. PMID- 26904731 TI - In Vitro Screening for Abiotic Stress Tolerance in Potent Biocontrol and Plant Growth Promoting Strains of Pseudomonas and Bacillus spp. AB - Plant growth promoting rhizobacteria (PGPR) has been identified as a group of microbes that are used for plant growth enhancement and biocontrol for management of plant diseases. The inconsistency in performance of these bacteria from laboratory to field conditions is compounded due to the prevailing abiotic stresses in the field. Therefore, selection of bacterial strains with tolerance to abiotic stresses would benefit the end-user by successful establishment of the strain for showing desired effects. In this study we attempted to isolate and identify strains of Bacillus and Pseudomonas spp. with stress tolerance and proven ability to inhibit the growth of potential phytopathogenic fungi. Screening of bacterial strains for high temperature (50 degrees C), salinity (7% NaCl), and drought (-1.2 MPa) showed that stress tolerance was pronounced less in Pseudomonas isolates than in Bacillus strains. The reason behind this could be the formation of endospores by Bacillus isolates. Tolerance to drought was high in Pseudomonas strains than the other two stresses. Three strains, P8, P20 and P21 showed both salinity and temperature tolerance. P59 strain possessed promising antagonistic activity and drought tolerance. The magnitude of antagonism shown by Bacillus isolates was also higher when compared to Pseudomonas strains. To conclude, identification of microbial candidate strains with stress tolerance and other added characteristic features would help the end user obtain the desired beneficial effects. PMID- 26904732 TI - Evaluation of the Pattern of EPIYA Motifs in the Helicobacter pylori cagA Gene of Patients with Gastritis and Gastric Adenocarcinoma from the Brazilian Amazon Region. AB - The Helicobacter pylori is associated with the development of different diseases. The clinical outcome of infection may be associated with the cagA bacterial genotype. The aim of this study was to determine the EPIYA patterns of strains isolated from patients with gastritis and gastric adenocarcinoma and correlate these patterns with the histopathological features. Gastric biopsy samples were selected from 384 patients infected with H. pylori, including 194 with chronic gastritis and 190 with gastric adenocarcinoma. The presence of the cagA gene and the EPIYA motif was determined by PCR. The cagA gene was more prevalent in patients with gastric cancer and was associated with a higher degree of inflammation, neutrophil activity, and development of intestinal metaplasia. The number of EPIYA-C repeats showed a significant association with an increased risk of gastric carcinoma (OR = 3.79, 95% CI = 1.92-7.46, and P = 0.002). A larger number of EPIYA-C motifs were also associated with intestinal metaplasia. In the present study, infection with H. pylori strains harboring more than one EPIYA-C motif in the cagA gene was associated with the development of intestinal metaplasia and gastric adenocarcinoma but not with neutrophil activity or degree of inflammation. PMID- 26904733 TI - Study of the Antibacterial Efficacy of Bainiku-Ekisu against Pathogens. AB - The research was undertaken to determine the bacteriostatic effects of the concentrate of Japanese apricot juice (bainiku-ekisu), which is a popular health food in Taiwan and Japan, on Enterococcus faecalis ATCC 29212, Staphylococcus aureus ATCC 25923, and Escherichia coli ATCC 25922. The results show that E. faecalis, S. aureus, and E. coli could be killed or inhibited by bainiku-ekisu at concentrations between 1.0 and 10.0 mg/mL. The minimum inhibitory concentration (MIC) was 1 mg/mL for all strains, and the minimum bactericidal concentrations (MBCs) were 5, 2.5, and 2.5 mg/mL for E. faecalis, S. aureus, and E. coli, respectively. Using the growth rate to calculate the MICs and MBCs, the MICs were 1.55, 1.43, and 0.97 mg/mL, and the MBCs were 2.59, 2.63, and 2.25 mg/mL for E. faecalis, S. aureus, and E. coli, respectively. According to the D values, E. faecalis and S. aureus exhibited lower resistance than E. coli at lower bainiku ekisu concentrations (1.0 and 2.5 mg/mL), and the resistance of these two pathogens was better than that of E. coli at higher bainiku-ekisu concentrations (5.0 and 10.0 mg/mL). The Z values of the E. faecalis, S. aureus, and E. coli strains were 3.47, 4.93, and 11.62 mg/mL, respectively. PMID- 26904734 TI - Activity of Aristolochia bracteolata against Moraxella catarrhalis. AB - A bioassay-guided fractionation of methanol extract of Aristolochia bracteolata whole plant was carried out in order to evaluate its antimicrobial activity and to identify the active compounds in this extract. Antibacterial and antifungal activities of methanol extract against gram-positive, gram-negative, and fungal strains were investigated by the agar disk diffusion method. Among the strains tested, Moraxella catarrhalis and sea urchin-derived Bacillus sp. showed the highest sensitivity towards the methanol extract and hence they are used as test organisms for the bioassay-guided fractionation. From this extract, aristolochic acid 1 (AA-1) has been isolated and has showed the greatest antibacterial activity against both standard strain and clinical isolates of Moraxella catarrhalis with equal minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 25 and 50 MUg/mL. Modification of the AA-1 to AA-1 methyl ester completely abolished the antibacterial activity of the compound and the piperonylic acid moiety of AA-1 which suggested that the coexistence of phenanthrene ring and free carboxylic acid is essential for AA-1 antibacterial activity. PMID- 26904735 TI - Isolation and Antimicrobial Susceptibility Patterns of Campylobacter Species among Diarrheic Children at Jimma, Ethiopia. AB - Introduction. Campylobacter is one of the leading bacterial causes of food-borne disease. The prevalence of Campylobacter species resistant to antimicrobial agents is increasing. This study is intended to determine prevalence and antimicrobial susceptibility patterns of Campylobacter species among under-five children with diarrhea. Methodology. A cross-sectional study was conducted among 227 under-five children with diarrhea from July to October 2012 at Jimma town. Isolation and identification of Campylobacter species were performed using standard bacteriological techniques. Antimicrobial susceptibility test was performed following standard protocol. Chi-square and Fisher's exact tests were used for analysis. Results. From 227 under-five children, 16.7% were positive for Campylobacter spp.; isolates, C. jejuni, C. coli, and C. lari, accounted for 71.1%, 21.1%, and 7.9%, respectively. Higher rate of resistance was observed to ampicillin 76.3%, trimethoprim-sulfamethoxazole (68.4%), tetracycline (39.5%), chloramphenicol (31.6%), clindamycin (26.3%), and doxycycline (23.7%). Erythromycin, ciprofloxacin, gentamicin, norfloxacin, and nalidixic acid were effective for more than 80% of the isolates. Multiple drug resistance was observed among 78.9% of all the three spp. Conclusions. Isolation rate of Campylobacter spp. was high. C. lari was reported for the first time at this study area. Higher rate of resistance was observed to the commonly used drugs. PMID- 26904736 TI - The Assessment of Viability of M. Tuberculosis after Exposure to CPC Using Different Methods. AB - Settings. National Institute for Research in Tuberculosis, Chennai. Objective. To assess the proportion of metabolically active cells of Mycobacterium tuberculosis after exposed to CPC using FDA-EB vital staining and viable counts on LJ medium. Mycolic acid content in M. tuberculosis after exposure to CPC was estimated using HPLC. Methods. Clinical isolates of M. tuberculosis and standard reference strain M. tuberculosis H37Rv were used for FDA-EB, viable count, and HPLC. Results. FDA/EB consistently stained 70-90% of log phase cells as green and the remaining cells as red-orange. After CPC treatment, 65-70% of the cells stained red-orange. The viability counts were comparable to 0-day controls. Synthesis of mycolic acids in mycobacteria was reduced when exposed to CPC using HPLC due to the decreased metabolic activity of the organisms. Conclusion. The cells are metabolically inactive during storage with CPC but these cells grew well on LJ medium after removal of CPC. The viability of M. tuberculosis was maintained in CPC with minimal reduction. Mycolic acid content was reduced if the cells of M. tuberculosis were treated with CPC for 7 days. All the above findings provide yet another evidence for the damage of cell wall of M. tuberculosis. PMID- 26904737 TI - Changing Trends in Prevalence and Antibiotics Resistance of Uropathogens in Patients Attending the Gondar University Hospital, Northwest Ethiopia. AB - Background. In most hospitals of developing countries, urinary tract infections are treated empirically because of lack of culture facilities. This leads to emergence of multiresistant uropathogens. Culturing and drug susceptibility testing are essential to guide therapy. Objectives. To assess changing prevalence and resistance pattern of uropathogens to commonly used antibiotics in a two-year study period. Methods. Urine specimens were collected and cultured. Uropathogens were identified by standard methods and tested for antibiotics resistance. Data were analyzed using SPSS version 16 statistical sofware. P value < 0.05 was considered statistically significant. Results. The commonest isolates in both the previous and present studies were E. coli, Klebsiella, CoNS, S. aureus, Proteus, and Citrobacter species. Previous isolates of Enterobacteriaceae were 100% sensitive to ciprofloxacin, whereas present isolates developed 31% to 60% resistance to it. Previous isolates were less resistant to gentamycin than the present ones. Multiresistance isolates were predominant in present study than previous ones. Conclusion. E. coli was predominant in the two study periods. Present isolates were more resistant than previous ones. Some previous isolates were 100% sensitive to ciprofloxacin, whereas present isolates were increasingly resistant. Ciprofloxacin and gentamicin have been recommended for empiric treatment of urinary tract infections. PMID- 26904738 TI - The Frequency of Methicillin-Resistant Staphylococcus aureus and Coagulase Gene Polymorphism in Egypt. AB - The current study aimed to use Coagulase gene polymorphism to identify methicillin-resistant Staphylococcus aureus (MRSA) subtypes isolated from nasal carriers in Minia governorate, Egypt, evaluate the efficiency of these methods in discriminating variable strains, and compare these subtypes with antibiotypes. A total of 400 specimens were collected from nasal carriers in Minia governorate, Egypt, between March 2012 and April 2013. Fifty-eight strains (14.5%) were isolated and identified by standard microbiological methods as MRSA. The identified isolates were tested by Coagulase gene RFLP typing. Out of 58 MRSA isolates 15 coa types were classified, and the amplification products showed multiple bands (1, 2, 3, 4, 5, and 8 bands). Coagulase gene PCR-RFLPs exhibited 10 patterns that ranged from 1 to 8 fragments with AluI digestion. Antimicrobial susceptibility testing with a panel of 8 antimicrobial agents showed 6 different antibiotypes. Antibiotype 1 was the most common phenotype with 82.7%. The results have demonstrated that many new variants of the coa gene are present in Minia, Egypt, different from those reported in the previous studies. So surveillance of MRSA should be continued. PMID- 26904739 TI - Detection of Q Fever Specific Antibodies Using Recombinant Antigen in ELISA with Peroxidase Based Signal Amplification. AB - Currently, the accepted method for Q fever serodiagnosis is indirect immunofluorescent antibody assay (IFA) using the whole cell antigen. In this study, we prepared the recombinant antigen of the 27-kDa outer membrane protein (Com1) which has been shown to be recognized by Q fever patient sera. The performance of recombinant Com1 was evaluated in ELISA by IFA confirmed serum samples. Due to the low titers of IgG and IgM in Q fever patients, the standard ELISA signals were further amplified by using biotinylated anti-human IgG or IgM plus streptavidin-HRP polymer. The modified ELISA can detect 88% (29 out of 33) of Q fever patient sera collected from Marines deployed to Iraq. Less than 5% (5 out of 156) of the sera from patients with other febrile diseases reacted with the Com1. These results suggest that the modified ELISA using Com1 may have the potential to improve the detection of Q fever specific antibodies. PMID- 26904740 TI - Antibiofilm Activity of Manuka Honey in Combination with Antibiotics. AB - We assessed the in vitro activity of Manuka honey against biofilm bacteria in combination with antibiotics and visualized the effect of Manuka honey on bacterial biofilms using scanning electron microscopy. The fractional biofilm eradication concentration (?FBEC) index for vancomycin plus Manuka honey against S. aureus IDRL-4284 biofilms was 0.34, indicating a synergistic interaction. The ?FBEC index for gentamicin plus Manuka honey against P. aeruginosa PAO1 biofilms was 0.78-0.82, indicating an additive interaction. Scanning electron microscopy of S. aureus IDRL-4284 and P. aeruginosa PAO1 biofilms exposed to Manuka honey and artificial honey containing the same sugar composition as Manuka honey showed that the former had more pronounced effects than the latter on both S. aureus and P. aeruginosa biofilms. Visualized effects included distorted cell morphologies for both bacteria and a decrease in P. aeruginosa extracellular matrix. In conclusion, Manuka honey has a synergistic interaction with vancomycin against S. aureus biofilms and an additive interaction with gentamicin against P. aeruginosa biofilms. PMID- 26904741 TI - Phylogenetic Framework and Biosurfactant Gene Expression Analysis of Marine Bacillus spp. of Eastern Coastal Plain of Tamil Nadu. AB - The present study emphasizes the diversity assessment of marine Bacillus species with special reference to biosurfactant production, respective gene expression, and discrimination among Bacillus licheniformis and Bacillus subtilis. Among the 200 individual species of eastern coastal plain of Tamil Nadu screened, five biosurfactant producing potential bacterial species with entirely different morphology were selected. Biochemical and 16S rRNA gene sequence analysis suggested that all the said five species belong to Bacillus genera but differ in species levels. Biosurfactant of all the five species fluctuates in greater levels with respect to activity as well as to constituents but showed partial similarity to the commercially available surfactin. The expression of srf gene was realized in all of the five species. However, the sfp gene expression was observed only in three species. In conclusion, both B. licheniformis and B. subtilis demonstrate srf gene; nevertheless, sfp gene was expressed only by Bacillus subtilis. PMID- 26904742 TI - Bacterial Biodegradation of Crude Oil Using Local Isolates. AB - An experimental study was undertaken to assess the efficiency of Pseudomonas aeruginosa, Bacillus subtilis, and Acinetobacter lwoffi isolated from petroleum contaminated water and soil samples to degrade crude oil, separately and in a mixed bacterial consortium. Capillary gas chromatography was used for testing the effect of those bacterial species on the biodegradation of crude oil. Individual bacterial cultures showed less growth and degradation than did the mixed bacterial consortium. At temperature 22 degrees C, the mixed bacterial consortium degraded a maximum of 88.5% of Egyptian crude oil after 28 days of incubation. This was followed by 77.8% by Pseudomonas aeruginosa, 76.7% by Bacillus subtilis, and 74.3% by Acinetobacter lwoffi. The results demonstrated that the selected bacterial isolates could be effective in biodegradation of oil spills individually and showed better biodegradation abilities when they are used together in mixed consortium. PMID- 26904743 TI - Highly Sensitive Loop-Mediated Isothermal Amplification for the Detection of Leptospira. AB - Leptospirosis is a worldwide zoonosis caused by an infection with the pathogenic species of Leptospira. We have developed a loop-mediated isothermal amplification (LAMP) assay to detect the DNA of Leptospira spp. Six sets of primers targeting the gene of the subsurface protein, lipL32, were evaluated for their detection sensitivity. The best primer set detected less than 25 copies of lipL32 per reaction of both plasmid DNA template and purified leptospiral genomic DNA. By combining primers targeting lipL32 with the previously published primer set targeting lipL41, the sensitivity of the assay was improved to 12 copies of L. interrogans. The specificity of the LAMP assay was evaluated by using the genomic DNA from other clinically encountered bacterial species such as different strains of Orientia tsutsugamushi, Rickettsia typhi, Rickettsia conorii, Rickettsia rickettsii, Coxiella burnetii, and Bartonella bacilliformis. These genomic DNA samples were all negative in our LAMP assay. The sensitivity of the LAMP assay was very similar to that of quantitative real time PCR. Several detection methods for the amplified product of LAMP assay were performed to demonstrate the simplicity of the assay. In summary, our results have suggested that this assay is rapid, robust, and easy to perform and has the potential to be used in endemic locations. PMID- 26904744 TI - Antibacterial Effects of Cissus welwitschii and Triumfetta welwitschii Extracts against Escherichia coli and Bacillus cereus. AB - Antibiotic resistance has increased sharply, while the pace for the development of new antimicrobials has slowed down. Plants provide an alternative source for new drugs. This study aimed to screen extracts from Cissus welwitschii and Triumfetta welwitschii for antibacterial activity against Escherichia coli and Bacillus cereus. The tests conducted included a susceptibility determination test, analysis of the effect of T. welwitschii on cell wall integrity, and transport across the membrane. It was found that the T. welwitschii methanol extracts were more effective than the water extracts and had the lowest minimum inhibitory concentration and minimum bactericidal concentration at 0.125 mg/mL and 0.5 mg/mL, respectively, against E. coli and B. cereus. The C. welwitschii extract caused the most drug accumulation in E. coli. In B. cereus, no significant drug accumulation was observed. Nucleic acid leakage in B. cereus and E. coli and protein leakage in E. coli were observed after exposure to the T. welwitschii extract. The extracts from T. welwitschii had greater antibacterial activity than the extracts from C. welwitschii. T. welwitschii may be a potential source of lead compounds for that could be developed into antibacterial agents. PMID- 26904745 TI - Hyaluronidase in Clinical Isolates of Propionibacterium acnes. AB - Objectives. We sought to describe the prevalence of a hyaluronidase gene and hyaluronidase production in 197 clinical isolates of P. acnes; we assessed kinetics of hyaluronidase production in a subset of three isolates. Methods. The hyaluronidase gene was detected using polymerase chain reaction. Hyaluronidase production was detected by growing isolates on BHI agar containing 400 MUg/mL hyaluronic acid and 1% albumin and flooding plates with 2 N glacial acetic acid to precipitate unbound hyaluronic acid, with a zone of clearing representing a positive phenotype. Hyaluronidase production kinetics were measured as a function of hyaluronic acid digestion over time in a liquid medium. Results. A hyaluronidase gene and hyaluronidase production were detected in 100 and 97% of P. acnes isolates, respectively. Hyaluronidase production in liquid medium was detectable after 96 hours of growth. Conclusions. Hyaluronidase production is nearly universal among P. acnes isolates. Three days appear to be required for significant hyaluronidase production in a liquid medium. Detection of hyaluronidase in tissue specimens may be a strategy to differentiate P. acnes infection from colonization when P. acnes is isolated from a clinical specimen. PMID- 26904746 TI - Bacterial Contamination of Medical Doctors and Students White Coats at Kilimanjaro Christian Medical Centre, Moshi, Tanzania. AB - Background. Microbial transmission from patient to patient has been linked to transient colonization of health care workers attires. Contamination of health care workers' clothing including white coats may play a big role in transmission of microbes. Study Objective. This study was conducted to determine the type of bacterial contamination on the white coats of medical doctors and students and associated factors. Methods. A cross-sectional study with purposive sampling of the bacterial contamination of white coats was undertaken. Demographic variables and white coats usage details were captured: when the coat was last washed, frequency of washing, washing agents used, and storage of the white coats. Swabs were collected from the mouth of left and right lower pockets, sleeves, and lapels of white coat in sterile techniques. Results. Out of 180 participants involved in the current study, 65.6% were males. Most of the coats were contaminated by staphylococci species and other bacteria such as Gram negative rods. Conclusion and Recommendations. White coats are potential source of cross infection which harbour bacterial agents and may play a big role in the transmission of nosocomial infection in health care settings. Effort should be made to discourage usage of white coats outside clinical areas. PMID- 26904747 TI - A Rapid and Sensitive Diagnostic Screening Assay for Detection of Mycobacteria Including Mycobacterium tuberculosis Directly from Sputum without Extraction. AB - We report a novel approach utilising a real-time PCR screening assay targeting a 53 bp tandemly repeated element present at various loci within the Mycobacterium tuberculosis (Mtb) genome. Positive samples were identified within a discriminatory melting curve range of 90-94 degrees C, with results obtained in under one hour directly from decontaminated sputum samples without extraction. A panel of 89 smear-positive sputa were used for analytical validation of the assay with 100% concordance, with sensitivity matching that of culture. Cross reactivity was detected within a narrow range of mycobacteria other than tuberculosis (MOTT) (five sputa, three in silico), with the highest sensitivity within M. avium complex (MAC). A year-long head to head evaluation of the test with the GeneXpert platform was carried out with 104 consecutive samples at the Royal Free Hospital, UK. Receiver operating characteristics (ROC) analysis of the data revealed that the two tests are approximately equivalent in sensitivity, with the area under the curve being 0.85 and 0.80 for the GeneXpert and our assay, respectively, indicating that the test would be a cost effective screen prior to GeneXpert testing. PMID- 26904748 TI - Role of Burkholderia pseudomallei Sigma N2 in Amino Acids Utilization and in Regulation of Catalase E Expression at the Transcriptional Level. AB - Burkholderia pseudomallei is the causative agent of melioidosis. The complete genome sequences of this pathogen have been revealed, which explain some pathogenic mechanisms. In various hostile conditions, for example, during nitrogen and amino acid starvation, bacteria can utilize alternative sigma factors such as RpoS and RpoN to modulate genes expression for their adaptation and survival. In this study, we demonstrate that mutagenesis of rpoN2, which lies on chromosome 2 of B. pseudomallei and encodes a homologue of the sigma factor RpoN, did not alter nitrogen and amino acid utilization of the bacterium. However, introduction of B. pseudomallei rpoN2 into E. coli strain deficient for rpoN restored the ability to utilize amino acids. Moreover, comparative partial proteomic analysis of the B. pseudomallei wild type and its rpoN2 isogenic mutant was performed to elucidate its amino acids utilization property which was comparable to its function found in the complementation assay. By contrast, the rpoN2 mutant exhibited decreased katE expression at the transcriptional and translational levels. Our finding indicates that B. pseudomallei RpoN2 is involved in a specific function in the regulation of catalase E expression. PMID- 26904750 TI - Review on the Antimicrobial Resistance of Pathogens from Tracheal and Endotracheal Aspirates of Patients with Clinical Manifestations of Pneumonia in Bacolod City in 2013. AB - Microbiological content specifically bacterial and fungal etiologies from tracheal aspirates in a tertiary hospital in Bacolod City was reviewed for baseline information. A total of 130 tracheal aspirates were subjected for culture to isolate and identify the pathogen and determine their susceptibilities to various antibiotics. Productions of certain enzymes responsible for antibiotic resistance like ESBL (Extended Spectrum Beta-Lactamase), metallo-beta-lactamase, and carbapenemase were also studied. Out of 130 specimens, 69.23% were found to be positive for the presence of microorganisms. Most infections were from male patients aging 60 years and above, confined at the Intensive Care Units (ICU). Pseudomonas aeruginosa and Klebsiella pneumoniae were found to be the most frequent bacterial isolates and non-Candida albicans for fungal isolates, respectively. Among the various antibiotics tested, most isolates were found to be resistant to third generation cephalosporins and penicillins, but susceptible to aminoglycoside Amikacin. On the other hand, production of ESBL and carbapenemase was found to be common among members of Enterobacteriaceae especially K. pneumoniae. PMID- 26904749 TI - Inhibition of Quorum Sensing-Controlled Virulence Factors and Biofilm Formation in Pseudomonas aeruginosa by Culture Extract from Novel Bacterial Species of Paenibacillus Using a Rat Model of Chronic Lung Infection. AB - Quorum sensing (QS) is a key regulator of virulence factors and biofilm formation in Gram-negative bacteria such as Pseudomonas aeruginosa. Microorganisms that inhabit soil are of strategic importance in the discovery of compounds with anti QS properties. The objective of the study was to test the culture extract of a taxonomically novel species of Paenibacillus strain 139SI for its inhibitory effects on the QS-controlled virulence factors and biofilm formation of Pseudomonas aeruginosa both in vitro and in vivo. The Paenibacillus sp. culture extract was used to test its anti-QS effects on the LasA protease, LasB elastase, pyoverdin production, and biofilm formation of P. aeruginosa as well as evaluate its therapeutic effects on lung bacteriology, pathology, hematological profile, and serum antibody responses of experimental animals in a rat model of chronic lung infection. Results showed significant decrease in the activities of QS controlled LasA protease, LasB elastase pyoverdin, and biofilm formation of P. aeruginosa caused by the culture extract. Moreover, the extract significantly prolonged the survival times of rats and facilitated the clearance of biofilm infections from infected lungs. In conclusion, the antiquorum sensing effects of culture extract from a novel species of Paenibacillus provide new insights to combat biofilm-associated infections. PMID- 26904751 TI - Corrigendum to "Influence of a Diester Glucocorticoid Spray on the Cortisol Level and the CCR4(+) CD4(+) Lymphocytes in Dogs with Atopic Dermatitis: Open Study". AB - [This corrects the article DOI: 10.1155/2014/492735.]. PMID- 26904752 TI - Prevention and Personal Responsibility. PMID- 26904753 TI - Shiga Toxin (Stx) Classification, Structure, and Function. AB - Shiga toxin (Stx) is one of the most potent bacterial toxins known. Stx is found in Shigella dysenteriae 1 and in some serogroups of Escherichia coli (called Stx1 in E. coli). In addition to or instead of Stx1, some E. coli strains produce a second type of Stx, Stx2, that has the same mode of action as Stx/Stx1 but is antigenically distinct. Because subtypes of each toxin have been identified, the prototype toxin for each group is now designated Stx1a or Stx2a. The Stxs consist of two major subunits, an A subunit that joins noncovalently to a pentamer of five identical B subunits. The A subunit of the toxin injures the eukaryotic ribosome and halts protein synthesis in target cells. The function of the B pentamer is to bind to the cellular receptor, globotriaosylceramide, Gb3, found primarily on endothelial cells. The Stxs traffic in a retrograde manner within the cell, such that the A subunit of the toxin reaches the cytosol only after the toxin moves from the endosome to the Golgi and then to the endoplasmic reticulum. In humans infected with Stx-producing E. coli, the most serious manifestation of the disease, hemolytic-uremic syndrome, is more often associated with strains that produce Stx2a rather than Stx1a, and that relative toxicity is replicated in mice and baboons. Stx1a and Stx2a also exhibit differences in cytotoxicity to various cell types, bind dissimilarly to receptor analogs or mimics, induce differential chemokine responses, and have several distinctive structural characteristics. PMID- 26904754 TI - Author's reply. PMID- 26904755 TI - Author's Reply. PMID- 26904756 TI - Author's Reply. PMID- 26904757 TI - Author's Reply. PMID- 26904758 TI - [Not Available]. PMID- 26904759 TI - [Not Available]. PMID- 26904760 TI - [Not Available]. PMID- 26904761 TI - New drugs and dosage forms. PMID- 26904763 TI - Nina Wedell. PMID- 26904762 TI - How nature copes with climate change. AB - As the world is about to find out whether or not our civilisation is up to the challenge of dealing with climate change, research shows a wide range of responses from other species, which may benefit or suffer from the change, and mitigate it or make it worse. Michael Gross reports. PMID- 26904764 TI - A MEDICAL STUDENT'S PERSPECTIVE ON ANIMAL EXPERIMENTATION. PMID- 26904765 TI - Pleomorphic plasma cell leukemia. PMID- 26904766 TI - Irwin Feigin, MD May 13, 1915-January 22, 2015. PMID- 26904767 TI - Lysia K.S. Forno, MD February 14, 1918-May 8, 2015. PMID- 26904768 TI - Margaret Grace Norman, MD, FRCP(C) October 19, 1933-May 17, 2015. PMID- 26904769 TI - [Attitudes and opinions of general practitioners and lung specialists about a new medicines counselling service for asthma patients in community pharmacies: a qualitative study]. AB - INTRODUCTION: Since October 2013, pharmacists can offer a new medicines counselling service (NMC). to asthma patients, who start a treatment with an inhaled corticosteroid. Although this individualized service can be organized at the request of the general practitioner (GP). the patient or the pharmacist, the uptake remains quite low. The limited involvement of GPs has already been identified as one of the obstacles to the successful implementation of this project. OBJECTIVE: To explore the attitudes and opinions of GPs and pulmonologists about NMC. METHOD: Focus group discussions with GPs were organized during eight meetings of local quality groups in the province of Antwerp, at which a total of 72 physicians were present. Also, five pulmonologists and two GPs with expertise in organization of primary healthcare participated in an interview. RESULTS: A large group of GPs was not aware of the existence of NMC and only a small number of them had experience with it. Nearly all pulmonologists and GPs agreed that repetition of the inhalation technique and follow-up of the adherence are useful. However, there was disagreement about the importance of taking the Asthma Control Test and explaining the pathology by the pharmacist. We could find five barriers that made physicians withhold support for the NMC. The most important obstacle seemed to be that the pharmacist is not obligated to communicate with the physician about the service. In addition, mainly GPs believed that the remuneration is too high and too focused on the number of NMC services performed and that pharmacists enter their domain with delivering this service. Both pulmonologists and GPs were concerned about how the pharmacist will include patients in a NMC, because it isn't always clear what the indication is of the prescribed inhaled corticosteroid. Furthermore, everyone was convinced that the inclusion criteria should be extended, since each patient using inhalation therapy, would benefit from additional support. Finally, some physicians had an objection to the fact that pharmacists are not obliged to follow an additional course before providing the service. CONCLUSION: The opinions of GPs about NMC were mixed and rather critical, while pulmonologists were somewhat more enthusiastic about the initiative. Although all physicians agreed that there is room for improvement of the concept, some GPs are willing to prescribe BNM for certain patients. PMID- 26904770 TI - Author's response. PMID- 26904771 TI - Interview With Nancy Borkowski, DBA, FACHE, CPA, Professor in the Department of Health Services Administration, University of Alabama at Birmingham. PMID- 26904772 TI - Developing Physician Leaders Through Professional Associations. PMID- 26904773 TI - Understanding Value-Based Incentive Models and Using Performance as a Strategic Advantage. PMID- 26904774 TI - Exploring Business Strategy in Health Information Exchange Organizations. AB - Unlike consumer goods industries, healthcare has been slow to implement technolo gies that support exchange of data in patients' health records. This results in avoid able medication errors, avoidable hospital readmissions, unnecessary duplicate testing, and other inefficient or wasteful practices. Community-based regional health information exchange (HIE) organizations have evolved in response to federal aims to encourage interoperability, yet little is known about their strategic approach. We use the lens of institutional and strategic management theories to empirically explore the differences in business strategies deployed in HIEs that are, to date, financially sustainable versus those that are not. We developed a 20-question survey targeted to CEOs to assess HIE business strategies. Our sample consisted of 60 community-based exchanges distributed throughout the United States, and we achieved a 58% response rate. Questions centered on competitive strategy and financial sustainability. We relied on logistic regression methods to explore relationships between variables. Our regression identified characteristics common to sustainable organizations. We defined sustainability as revenues exceeding operational costs. Seventeen of the 35 organizations (49%) defined themselves as currently sustainable. Focus and cost leadership strategies were significantly associated with sustainability. Growth strate gies, which were much more common than other strategies, were not associated with sustainability. We saw little evidence of a differentiation strategy (i.e., the basis of competition whereby the attributes of a product or service are unmatched by rivals). Most CEOs had a relatively optimistic outlook, with 60% stating they were confident of surviving over the next 5 years; however, nearly 9% of the organizations were in some phase of divestiture or exit from the market. HIEs are evolving differently based on local leadership decisions, yet their strategic approach is isomorphic (or similar). Further insight into successful business strategies could help ensure the long-term survival of HIEs. PMID- 26904775 TI - Practitioner Application. PMID- 26904777 TI - Practitioner Application. PMID- 26904776 TI - The Effects of Hospital-Level Factors on Patients' Ratings of Physician Communication. AB - The quality of physician-patient communication influences patient health outcomes and satisfaction with healthcare delivery. Yet, little is known about contextual factors that influence physicians' communication with their patients. The main purpose of this article is to examine organizational-level factors that influence patient perceptions of physician communication in inpatient settings. We used the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey and American Hospital Association data to determine patients' ratings of physician communication at the hospital level, and to collect information about hospital-level factors that can potentially influence physician communication. Our sample consisted of 2,756 hospitals. We ran a regression analysis to determine the predictors of poor physician communication, measured as the percentage of patients in a hospital who reported that physicians sometimes or never communicated well. In our sample of hospitals, this percentage ranged between 0% and 21%, with 25% of hospitals receiving poor ratings from more than 6% of patients. Three organizational factors had statistically significant negative associations with physician communication: for-profit ownership, hospital size, and hospitalists providing care in the hospital, On the other hand, the number of full-time-equivalent physicians and dentists per 10,000 inpatient days, physician ownership of the hospital, Medicare share of inpatient days, and public ownership were positively associated with patients' ratings of physician communication. Physician staffing levels are an understudied area in healthcare research. Our findings indicate that physician staffing levels affect the quality of physician communication with patients. Moreover, for-profit and larger hospitals should invest more in physician communication given the role that HCAHPS plays in value-based purchasing. PMID- 26904778 TI - A Review of Tools to Assist Hospitals in Meeting Community Health Assessment and Implementation Strategy Requirements. AB - Recent changes in U.S. national policies and regulations have created an opportunity for meaningful collaborations to take place between health systems, public health departments, and social service organizations. For medical systems, and particularly tax-exempt hospitals, new requirements include community health assessments (CHAs) and implementation strategies to address identified health needs. Individuals and groups responsible for meeting the new CHA and implementation strategy requirements may be unsure about the best ways to achieve specific aspects of the CHA process. In this report, we provide an in-depth review and rating of tools developed by public health and community experts that cover the steps necessary to meet the new requirements. A team of three community and public health experts and the authors developed a rating sheet based on a well-known community health improvement process model and on the steps in the new requirements to identify and systematically rate nine comprehensive tools. The ratings and recommendations provide a guide for hospitals in choosing tools that will best assist them in meeting the new requirements. PMID- 26904779 TI - Practitioner Application. PMID- 26904781 TI - Practitioner Application. PMID- 26904780 TI - The Capital Budgeting Process of Healthcare Organizations: A Review of Surveys. AB - Several surveys have been administered over the last 40 plus years to learn about capital budgeting practices of healthcare organizations. In this report, we analyze and synthesize these surveys in a four-stage framework of the capital budgeting process: identification, development, selections, and post-audit. We examine three issues in particular: (1) efficiency of for-profit hospitals relative to not-for-profit hospitals, (2) capital budgeting practices of the healthcare industry vis-a-vis other industries, and (3) effects of healthcare mergers and acquisitions on capital budgeting decisions. We found indirect evidence that for-profit hospitals exhibited greater efficiency than not-for profit hospitals in recent years. The acquisition of not-for-profits by for profits is credited as the primary reason for growth of multihospital systems; these acquisitions may have contributed to the more efficient capital budgeting practices. One unique attribute of healthcare is the dominant role of physicians in almost all aspects of the capital budgeting process. In agreement with some researchers, we conclude that the disproportionate influence of physicians is likely to impede efficient decision making in capital budgeting, especially for nonprofit organizations. PMID- 26904782 TI - Imitation, The Greatest Form of Flattery? PMID- 26904783 TI - A Correct Diagnosis is of Increasing Importance. PMID- 26904784 TI - A Review of Craniofacial Referrals to the NPCC and Introduction of a New Referral Pathway. PMID- 26904785 TI - Screening for Chlamydia is acceptable and feasible during Cervical Screening in General Practice. AB - The incidence of Chlamydia trachomatis (CT) & Neisseria gonorrhoeae (NG) are rising in Ireland. Both are often undiagnosed and may cause infertility amongst other complications. CT/NG screening is not routinely offered during cervical cancer screening. This study aimed to ascertain the feasibility and acceptability of screening for CT/NG at time of smear and to measure the diagnostic yield. Screening was offered to women aged 25-40 years attending four participating general practices as part of Cervical Check. A retrospective review of the three months preceding the study period, indicated that out of 138 smears, CT/NG testing was performed in 10 (7%) of cases. 236 (93%) patients consented to screening for CT/NG. The detection rate for Chlamydia was 6 (2.4%), with no positive results for NG. Feedback from patients was positive. Interestingly, 42 (18%) of participants who completed the questionnaire believed STI screening was already part of the routine smear. PMID- 26904786 TI - The Positive Impact of Bariatric Surgery on Sleep. AB - Between June 2009 and July 2012, Apnoea-Hypopnoea Index (AHI) and Functional Outcomes of Sleep Questionnaires Scores (FOSQ) were prospectively evaluated pre- and post-operatively in patients undergoing bariatric surgery. A total of 167 subjects were studied, 75.4% were females. The median age was 46 (14-75) years and BMI 49 (36-69) kg/m2. Ninety two (55.0%) patients were diagnosed with Obstructive Sleep Apnoea (OSA) preoperatively. Fifty (54.0%) required positive airway pressure (PAP) therapy. The mean reduction in BMI post bariatric surgery was 12.2 +/- 4.52 kg/m2 at 6.56 +/- 2.70 months. Eighty (87.9%) reported improved sleep quality reflected in improved scores in all domains of the FOSQ (p < 0.001, paired t-test). Improvement in FOSQ scores remained significant (p < 0.05) in those with and without OSA. Thirty-nine (90.7%) patients discontinued PAP due to resolution of daytime sleepiness. In conclusion, weight loss following bariatric surgery has a positive impact on sleep in-patients with and without OSAS. PMID- 26904787 TI - Examining the End-User Experience of the National Integrated Medical Imaging System (NIMIS). AB - The National Integrated Medical Imaging System (NIMIS) is used to store and retrieve medical imaging studies in Ireland. The purpose of this audit was to obtain feedback from its end-users in relation to key NIMIS functionality and to understand their perception of its existing interface while identifying potential improvements. The results showed that, while the majority of respondents are satisfied with NIMIS, they identified a number of areas of concern. These included difficulty in identifying the appropriate code for a study, 88 (34%); dissatisfaction with ordering and viewing scans, 82 (32%); and a need for improved communication between end-users and local Radiology departments, with 104 (40%) unsure when to contact the department and 137 (53%) dissatisfied with the feedback they received in relation to requests. Respondents indicated that addressing these issues would improve the NIMIS end-user experience while allowing it to continue to meet current and future clinical needs. PMID- 26904788 TI - Standards in Operation Notes--Is It Time to Re-Emphasise Their Importance? AB - Guidelines exist for operation notes from the Royal College of Surgeons of England but compliance has been shown to be variable. The authors performed a closed loop audit of compliance with RCS standards in an Irish Plastic Surgery department. Thirty random operation notes were selected from a conserved pool of authors--before and after an educational intervention to increase awareness of the RCS guidelines. Following education, improvements were noted but also deteriorations--time increased from 12 (40%) to 16 (53%), emergency/elective status from none (0%) to 11 (36%), and operative diagnosis from seven (23%) to 21 (70%). However notably among the findings, surgeon's name decreased from 30 (100%) to 26 (86%), findings from 27 (90%) to 21 (53%) and tissue altered from 27 (90%) to 20 (66%). As some specialities are developing operation note standards specific to individual procedures, the findings are compared with previous similar published work. PMID- 26904789 TI - In-hospital Cardiac Arrest at Cork University Hospital. AB - We describe the incidence and outcomes of in-hospital cardiac arrest (IHCA) at Cork University Hospital over a one year time period (2011), prior to the implementation of national early warning scoring (NEWS) systems. There were 43 217 coded CUH admissions, in 2011, to 518 in-patient beds. The Hospital In Patient Enquiry Database was used to identify adults (>/= 18 years) who sustained IHCA. Available Utstein variables were collected. Fifty-two patients were found to be incorrectly coded IHCA. 17 of 63 (27.0%) IHCA survived to discharge. IHCA with shockable rhythm had significantly higher survival. IHCA survival was significantly lower on wards versus any other hospital location. Median days of stay prior to arrest were significantly different between survivors and non survivors. All survivors (n = 17) had intact neurological outcome post-event. Our outcomes from IHCA are poorest on hospital wards when compared to other areas of the hospital. Those that survive have excellent function and one-year survival. PMID- 26904790 TI - The Value of the Combined Assessment of COPD in Accurate Characterization of Stable COPD. AB - There is evidence showing a tendency to upgrade COPD severity previously staged with spirometric-based GOLD (GOLD 1234) when using the new GOLD combined disease assessment (GOLD ABCD). The aim of our study was to compare the GOLD 1234 classification in a population of stable COPD patients with the GOLD ABCD classification to determine whether stable COPD was upgraded when using this new classification. After an observational study of a stable COPD cohort (n = 112), 61 patients (54.5%) had an increase in their COPD severity when moving from the old GOLD 1234 classification to the current GOLD ABCD assessment (p < 0.01). 42 patients (37.5%) had no change in severity of COPD. 9 patients COPD were assessed to be better on using GOLD ABCD. This study highlights previously missed high risk patients when reviewing stable COPD. Continued incorporation of GOLD ABCD will translate into better evidence-based management. PMID- 26904791 TI - The Clinical Utility of a Low Serum Ceruloplasmin Measurement in the Diagnosis of Wilson Disease. AB - The first step in screening for potential Wilson disease is serum ceruloplasmin testing, whereby a level of less than 0.2g/L is suggestive of the disease. We aimed to determine what proportion of an Irish population had a low ceruloplasmin level, whether low measurements were appropriately followed-up and what were the clinical outcomes. We conducted a retrospective review of all serum ceruloplasmin measurements between August 2003 and October 2009 in a large tertiary referral centre in Southern Ireland. Clinical data, serum ceruloplasmin, liver function tests, urinary copper and liver biopsy reports were all recorded where available. 1573 patients had a serum ceruloplasmin measurement during the 7-year study period. 96 patients (6.1%) had a ceruloplasmin level < 0.2g/L and of these only 3 patients had Wilson disease. There was only 1 new diagnosis. Only 27 patients (28.1%) had some form of confirmatory testing performed. In our centre's experience, the positive predictive value of a significantly low ceruloplasmin level is 11.1% (95% CI 2.91-30.3%). In practice a low serum ceruloplasmin measurement is often not followed by appropriate confirmatory testing. Measuring serum ceruloplasmin as a singular diagnostic test for Wilson disease or as part of the battery of unselected liver screening tests is inappropriate and low yield. PMID- 26904792 TI - Is the Current BST ePortfolio fulfilling its Role in the Training of Clinical Medicine SHOs? AB - While the objective recording of clinical competencies in an electronic portfolio (ePortfolio) has become a key aspect of basic specialist training (BST), it continues to divide opinion. We surveyed medical trainees and their supervisors in the Dublin region examining their views of the ePortfolio and workplace-based assessments (WPBAs). Responses were received from 27 of 149 (18.1%) SHOs and 24 of 307 (7.9%) consultants. Our results highlight significant dissatisfaction amongst trainees with 20 (74.1%) stating that the ePortfolio is not an effective educational tool. Consultants had more mixed views. While 16 (66.7%) reported that feedback sessions were useful for trainee development, only 4 (16.7%) found the ePortfolio to be useful in highlighting trainees' strengths and weaknesses. Although other studies have emphasised its educational potential, our results suggest that practical barriers, such as time constraints and a lack of training, lead to poor engagement and a negative view of the ePortfolio. PMID- 26904793 TI - Management of Patients with Subclinical Hypothyroidism in Primary Care. AB - Subclinical hypothyroidism (SCH) is defined as a raised serum thyroid stimulating hormone level with normal thyroxine. Despite a prevalence of up to 9% of the adult population there is widespread uncertainty on how to manage it. The aim of this study was to assess how older adults with SCH are managed in primary care. A retrospective case-note review was carried out on patients attending Mallow Primary Healthcare Centre. This study identified patients 65 years and over meeting the criteria for SCH in one year. The prevalence of SCH in this study was calculated as 2.9%. 22.2% of patients were treated with thyroxine. 6.1% of untreated patients progressed to clinical hypothyroidism within the study period while 18.2% spontaneously reverted to normal TSH levels. PMID- 26904794 TI - A Rare Cause of Testicular Pain: Thrombosis of the Pampiniform Plexus. AB - Testicular pain is a common presentation in the emergency department. The cause includes a wide array of differentials. This report highlights a case of thrombosis of the pampiniform plexus as a rare cause of testicular pain. Doppler ultrasound should be the first line investigation. Symptomatic relief with anti inflammatory medication should be sufficient for management. PMID- 26904795 TI - Gentamicin Dosing in Therapeutic Hypothermia; a Quality Improvement Initiative. PMID- 26904796 TI - The Tip of the Iceberg--'Never Ignore a Chronic Cough'. PMID- 26904797 TI - The Worrying Modern Scenario of Benign Pathology after Nephrectomy for Presumed Renal Cancer. PMID- 26904798 TI - [Multispectral Radiation Algorithm Based on Emissivity Model Constraints for True Temperature Measurement]. AB - Temperature measurement is one of the important factors for ensuring product quality, reducing production cost and ensuring experiment safety in industrial manufacture and scientific experiment. Radiation thermometry is the main method for non-contact temperature measurement. The second measurement (SM) method is one of the common methods in the multispectral radiation thermometry. However, the SM method cannot be applied to on-line data processing. To solve the problems, a rapid inversion method for multispectral radiation true temperature measurement is proposed and constraint conditions of emissivity model are introduced based on the multispectral brightness temperature model. For non blackbody, it can be drawn that emissivity is an increasing function in the interval if the brightness temperature is an increasing function or a constant function in a range and emissivity satisfies an inequality of emissivity and wavelength in that interval if the brightness temperature is a decreasing function in a range, according to the relationship of brightness temperatures at different wavelengths. The construction of emissivity assumption values is reduced from multiclass to one class and avoiding the unnecessary emissivity construction with emissivity model constraint conditions on the basis of brightness temperature information. Simulation experiments and comparisons for two different temperature points are carried out based on five measured targets with five representative variation trends of real emissivity. decreasing monotonically, increasing monotonically, first decreasing with wavelength and then increasing, first increasing and then decreasing and fluctuating with wavelength randomly. The simulation results show that compared with the SM method, for the same target under the same initial temperature and emissivity search range, the processing speed of the proposed algorithm is increased by 19.16%-43.45% with the same precision and the same calculation results. PMID- 26904799 TI - [Spectroscopic Diagnosis of Two-Dimensional Distribution of OH Radicals in Wire Plate Pulsed Corona Discharge Reactor]. AB - Pulsed corona discharge in atmosphere has been widely regarded as an efficient flue gas treatment technology for the generation of active radical species, such as the OH radicals. The spatial distribution of OH radicals generated by pulsed corona discharge plays an important role in decomposing pollutants. The two dimensional (2-D) distribution of OH radicals of positive wire--plate pulsed corona discharge was detected using laser-induced fluorescence (LIF). The influence of relative humidity (RH) and oxygen concentration on the 2-D distribution of OH radicals were investigated. The results indicated that the 2-D distribution of OH radicals was characterized by a fan-shaped distribution from the wire electrode to plate electrode, and both the maximum values of vertical length and horizontal width of the fan area was less than 1 cm. The 2-D distribution area of OH radicals increased significantly with increasing the RH and the optimum condition was 65% RH. The optimal level of the oxygen concentration for the 2-D distribution area of OH radicals was 2%. The process of OH radical generation and 2-D distribution area of OH radicals were significantly interfered when the oxygen concentration was larger than 15%. The total quenching rate coefficients for different RH values and oxygen concentration in this study were used to calculate the fluorescence yield of OH radical. The fluorescence yield, which is the ratio between the emission rate (Einstein coefficient) and the sum of the emission rate and quenching rate, was used to normalize the 2-D distribution area of OH radicals. The fluorescence yield of OH radical decreased with increasing the RH and oxygen concentration linearly and rapidly. It was also found that compared with the RH, the influence of the oxygen concentration had more notable effect on the fluorescence yield of OH radical and 2-D distribution area of OH radicals. PMID- 26904800 TI - [The Performance Analysis for Lighting Sources in Highway Tunnel Based on Visual Function]. AB - Under the condition of mesopic vision, the spectral luminous efficiency function is shown as a series of curves. Its peak wavelength and intensity are affected by light spectrum, background brightness and other aspects. The impact of light source to lighting visibility could not be carried out via a single optical parametric characterization. The reaction time of visual cognition is regard as evaluating indexes in this experiment. Under the condition of different speed and luminous environment, testing visual cognition based on vision function method. The light sources include high pressure sodium, electrodeless fluorescent lamp and white LED with three kinds of color temperature (the range of color temperature is from 1 958 to 5 537 K). The background brightness value is used for basic section of highway tunnel illumination and general outdoor illumination, its range is between 1 and 5 cd x m(-)2. All values are in the scope of mesopic vision. Test results show that: under the same condition of speed and luminance, the reaction time of visual cognition that corresponding to high color temperature of light source is shorter than it corresponding to low color temperature; the reaction time corresponding to visual target in high speed is shorter than it in low speed. At the end moment, however, the visual angle of target in observer's visual field that corresponding to low speed was larger than it corresponding to high speed. Based on MOVE model, calculating the equivalent luminance of human mesopic vision, which is on condition of different emission spectrum and background brightness that formed by test lighting sources. Compared with photopic vision result, the standard deviation (CV) of time-reaction curve corresponding to equivalent brightness of mesopic vision is smaller. Under the condition of mesopic vision, the discrepancy between equivalent brightness of different lighting source and photopic vision, that is one of the main reasons for causing the discrepancy of visual recognition. The emission spectrum peak of GaN chip is approximate to the wave length peak of efficiency function in photopic vision. The lighting visual effect of write LED in high color temperature is better than it in low color temperature and electrodeless fluorescent lamp. The lighting visual effect of high pressure sodium is weak. Because of its peak value is around the Na+ characteristic spectra. PMID- 26904801 TI - [Research on Properties of Light Scattering for Non-Spherical Suspended Particles in Water Based on T Matrix Model]. AB - Scattering light properties of suspended particles in water is an important parameter which influences the accuracy of water quality measurement. In this paper, based on T matrix model, the authors study the UV-Visible light irradiation intensity of 3 kinds of non-spherical suspended. particles including ellipsoid, cylinder and generalized Chebyshev in water. The relationship between light scattering intensity and incident light wavelength, shape parameters of suspended particles, complex refractive index and rotation angle has been presented in detail. Simulation results show that when changing the particle size, adjusting the wavelength of incident light, all light scattering intensity of 3 kinds of non-spherical suspended particles show significant changes. In the wavelength range from 200-800 nm, the impact of geometric on the particles size decreases with increasing wavelength and the sattering properites mainly depends on complex refractive index. The scattering intensity becomes stronger and exhibits strong oscillations for ultraviolet and infrared light when the diameter of particles are less than 0.2 MUm or approaching 1 MUm. However, the scattering intensity is relatively stable and close to zero, shows small disturbances with the change of wavelength of incident light when the particles sizes are within 0.3 to 0.9 MUm. PMID- 26904802 TI - [Reconstruction Research for Gas Concentration and Temperature of Flame Based on Algebraic Reconstruction Technique]. AB - We specify water vapor among combustion products as the target gas based on tunable diode absorption spectroscopy in this paper. The direct absorption signals of water vapor after being processed can be used to calculate the gas concentration distributions and temperature distributions of the combustion region of methane and air flat flame furnace via algebraic reconstruction technique (ART). In the numerical simulation, reconstruction region is a grid of five by five, we assume a temperature and water vapor concentration distribution of 25 grid, then simulate different direction laser rays which cross the combustion region, generating projection of each ray, by ART reconstruction algorithm, it turns out that the temperature and water vapor distribution reconstruction error is less than 1%. In the experiment, we chose a distributed feedback laser to scan the target gas H2O7 153.722, 7 153.748 and 7 154.354 cm( 1) as absorbtion line pair to measure temperature of the flame, we consider the former two line as one absorbtion line. By Stages multi-directional scanning, the authors abtain 16 different regions distributin of temperature and gas concentration of furnace when we collecte 30 different angle data by spectral data processing, reconstruction algorithm, two absorbtion line ratio method for temperature sensing, finding the temperature and water concentration are higher in the center than in the edge, it turns out that the reconstruction algorithm is good enough to achieve the distributions of gas concentration and temperature of the combustion region. PMID- 26904803 TI - [Investigation on Spectral Characteristics of Micro-Gap Dielectric Barrier Uniform Discharge in Air]. AB - The plasmas generated by dielectric barrier discharge in atmospheric pressure air have wide application prospect in industry. In order to study generation condition and mechanism, the dielectric barrier uniform discharge in atmospheric pressure air has been studied experimentally with a micro-gap discharge device. Results of electrical characteristics indicate that it exist several current pulses with short width in half period of the applied voltage at a low voltage, a large number of micro-discharge filaments are observed. The discharge power increases with increasing peak value of applied voltage, the micro-discharge filaments increase meanwhile. When the peak of applied voltage reaches to 9.2 kV, only a discharge hump with a width of about 5.5 MUs appears in a half period of the applied voltage, micro-discharge filaments cannot be discerned. The uniform discharge has been obtained finally as the micro-discharge filaments extend and superimpose randomly. The emission spectrum of dielectric barrier discharge scanning from 330 to 420 nm is collected. It is found that the intensity of 337.1 nm is stronger than that of 391.4 nm. If the intensity of 337.1 nm is considered as the datum reference, the intensity of 391.4 nm shows the magnitude of electron average energy. The molecule internal energy is evaluated by vibration temperature. The electron average energy and molecule internal energy have been investigated by optical emission spectra. It is found that both of them decrease with increasing the applied voltage. Results indicate that it is not easy to form filamentary discharge when the electrical energy is lower. The average electron energy of uniform discharge is lower than that of the filamentary discharge. These results are of great significance to the application of dielectric barrier uniform discharge obtained in air at atmospheric pressure. PMID- 26904804 TI - [Study on Spectral Characteristics of Micro Plasma Channels of Different Gas-Gap in Dielectric Barrier Discharge]. AB - By optical emission spectrum, we report on the first investigation on the plasma parameters of micro plasma channels which are generated in two gas-gaps with different thickness in a triple-layer dielectric barrier discharge system. Different from the micro plasma channels formed in traditional two-layer dielectric barrier discharge, micro plasma channels formed in the triple-layer dielectric barrier discharge system reflect a unique discharge characteristic. From the pattern images taken by an ordinary camera, it shows that micro plasma channels generated in two discharge gas-gaps discharge with different sizes and light intensities. The micro plasma channels in wide gas-gap are much bigger than those in narrow gas-gap, and their light intensities are obvious stronger. By collecting the emission spectra of N2 second positive band (C3?u --> B3?g ) and calculating the relative intensity ratio method of N2 molecular ion line at 391.4 and the N2 molecular line at 394.1, the molecular vibration temperature and the average electron energy of micro plasma channels in two gas-gaps as functions of Argon concentration and applied voltage are investigated, respectively. It is found that the molecular vibration temperature and the average electron energy of micro plasma channels in wide gas-gap are lower than those in narrow gas-gap, and they both decrease with the increasing of the Argon concentration. As the applied voltage increases, micro plasma channels in wide gas-gap vary in a small range on the above two plasma investigations, while those in narrow gas-gap vary obviously. It indicates that micro plasma channels in narrow gas-gap are more sensitive to the applied voltage and they have a wider variation range of electric field than those in wide gas-gap. PMID- 26904805 TI - [The Synthesis, Luminescence and Energy Transmission of NaLa(MoO4) 2 : Eu3+/Tb3+/Tm3+ Materials]. AB - A series of Eu3+ /Tb3+ /Tm3+ single/co-doped NaLa(MoO4)2 (NLM) phosphors have been synthesized by microemulsion-hydrothermal method. Phosphor crystal structure, morphology and luminescent properties were tested and studied by X-ray diffraction (XRD), scanning electron microscopy (SEM) and fluorescence spectroscopy. The results show that the prepared samples are all tetragonal single crystals. By way of substitution, the sites of La3+ are replaced by Eu3+, Tb3+ and Tm3+. Morphology of the samples are tetragonal sheet structure and the size of particles is 1 - 1.5 MUm. When the doping concentration of Eu3+ is 9%, NLM : 9%Eu3+ phosphor emission peak is the strongest at 616 nm, the critical transfer distance (R(c)) between Eu3+ in the NLM matrix is about 15.20 A at this time. At the emission spectrum of NLM : 9%Eu3+, the peak at 591 nm is the magnetic dipole transition of 5D0 to 7F1 of Eu3+. The peak at 616 nm is the electric dipole transition of 5D0 to 7 F2 of Eu3+. Electric dipole transition emission intensity is about 10 times of the strength of the magnetic dipole transition. This indicates that Eu3+ is located at noninversion symmetry site. By Fixing Eu3+ (Tb3+) concentration and varying the concentration of Tb3+ (Eu3+), the energy transfer mechanism between Eu3+ and Tb3+ was studied. By adjusting the Eu3+, Tb3+ and Tm3+ doping concentrations, tunable luminescence of visible light region is implemented under the single matrix. The luminescence of NLM x%Eu3+, y%Tb3+, z%Tm3+ phosphors are translated from blue (0.205, 0.135) to pseudo-white (0.305, 0.266) under 360 nm irradiation. PMID- 26904806 TI - [The Influence of Different Ionic Concentration in Cell Physiological Solution on Temperature Measurement by Near Infrared]. AB - It is important to real-timely monitor and control the temperature of cell physiological solution in patch clamp experiments, which can eliminate the uncertainty due to temperature and improve the measurement accuracy. This paper studies the influence of different ions at different concentrations in the physiological solution on precision of a temperature model by using near infrared spectroscopy and chemometrics method. Firstly, we prepared twelve sample solutions respectively with the solutes of CaCl2, KCl and NaCl at four kinds of concentrations, and collected the spectra of different solutions at the setting temperature range 20-40 degrees C, the range of the spectra is 9 615-5 714 cm( 1). Then we divided the spectra of each solution at different temperatures into two parts (a training set and a prediction set) by three methods. Interval partial least squares method was used to select an effective wavelength range and develop calibration models between the spectra in the selected range and temperature velues. The experimental results show that RMSEP of CaCl2 solution with 0.25 g x mL(-1) is maximum, the result of the three tests are 0.386 3, 0.303 7 and 0.337 2 degrees C, RMSEP of NaCl with 0.005 g x mL(-1) solution is minimum, the result of the three tests are 0.220 8, 0.155 3 and 0.145 2 degrees C. The experimental results indicate that Ca2+ has the greatest influence on the accuracy of the temperature model of the cell physiological solution, then K+, and Na+ has the least influence. And with the ionic concentration increasing, the model accuracy decreases. Therefore; when we build the temperature model of cell physiological solution, it is necessary to change the proportion of the three kinds of main ions in cell physiological solution reasonably in order to correct the effects of different ionic concentrations in physiological solution and improve the accuracy of temperature measurements by near infrared spectroscopy. PMID- 26904807 TI - [Preliminary Study on the Unique Spectroscopic Characteristics of Natural and Synthetic Diamonds]. AB - A systematic comparative study on the natural diamond, the natural diamond treated by heat or irradiation and synthetic diamond prepared by chemical vapor deposition (CVD) or High temperature and high pressure (HTHP) were carried out by UV-Vis-NIR absorption and FTIR spectra. The results showed that: natural diamond, treated natural samples such as irradiated or annealed ones under high temperature and the HTHP synthetic diamond, the reflection coefficient is obviously variation between 200 nm and 1100 nm in UV-Vis-NIR spectra of above samples. In contrast, the reflection coefficient of CVD synthetic diamond is relatively smaller than the former. Infrared spectra showed that synthetic diamonds, especially for CVD synthetic diamonds have no obvious absorption peak between 800 and 1 600 cm(-1). In additional, the results of DiamondView detection are different for different kinds of diamonds. Generally speaking, some CVD synthetic diamonds treated by HTHP appears some parallel dislocation lines, and show light-blue fluorescence. HPHT synthetic diamonds exhibit strong blocky geometrical shapes whereas some natural diamonds exhibit more tree-ring type fluorescence patterns, the color of diamonds' fluorescence image may change after treated by HTHP or irradiation. In a word, in view of the diversity and innovation of the synthesis technologies for diamond, the natural and synthetic diamonds have some similar spectra characteristic in term of UV-Vis-NIR and FTIR spectra, some special natural diamonds without typical spectra characteristic of natural ones need to be further supplemented with DiamondView, photoluminescence spectra and other instruments. PMID- 26904808 TI - [Study on the Application of NAS-Based Algorithm in the NIR Model Optimization]. AB - In this paper, net analysis signal (NAS)-based concept was introduced to the analysis of multi-component Ginkgo biloba leaf extracts. NAS algorithm was utilized for the preprocessing of spectra, and NAS-based two-dimensional correlation analysis was used for the optimization of NIR model building. Simultaneous quantitative models for three flavonol aglycones: quercetin, keampferol and isorhamnetin were established respectively. The NAS vectors calculated using two algorithms introduced from Lorber and Goicoechea and Olivieri (HLA/GO) were applied in the development of calibration models, the reconstructed spectra were used as input of PLS modeling. For the first time, NAS based two-dimensional correlation spectroscopy was used for wave number selection. The regions appeared in the main diagonal were selected as useful regions for model building. The results implied that two NAS-based preprocessing methods were successfully used for the analysis of quercetin, keampferol and isorhamnetin with a decrease of factor number and an improvement of model robustness. NAS-based algorithm was proven to be a useful tool for the preprocessing of spectra and for optimization of model calibration. The above research showed a practical application value for the NIRS in the analysis of complex multi-component petrochemical medicine with unknown interference. PMID- 26904809 TI - [Detection of Syrup Adulterants in Prepackaged Pure Pineapple Juice by Fourier Transform Infrared Spectroscopy and Chemometric Analysis]. AB - This study was performed to establish a method that can quickly and accurately identify adulterated syrup in the pure pineapple juice. A attenuated total internal refraction-fourier transform infrared spectroscopy was used to collect the range of 900 -1 500 cm(-1) infrared spectra of 234 samples pure pineapple juice and adulterated syrup by beet syrup, rice syrup and cassava syrup. By using linear discriminant analysis and support vector machine for the identification model, comparing the full spectral and selected wavelengths based on principal component analysis loading plots of the two models to identify adulteration. Studies showed that the correct rate of validation set by linear discriminant analysis and support vector machine model on full spectral were both higher than 88%, variables were significantly reduced from 312 to 8 after selecting the eight characteristic wavelengths, the correct rate of validation set by linear discriminant analysis model was up to 96.15% and support vector machine was increase to 94.87%. The results demonstrated that the model built using a attenuated total internal refraction-fourier transform infrared spectroscopy in combination with chemometric methods after selected characteristic wavelengths could be used for the identification of the adulterated syrup in the pure pineapple juice. PMID- 26904810 TI - [Study on Trace Water Influence on Electrical Properties of Insulating Oil Based on the Mid-Infrared Spectrum Analysis]. AB - Trace water has a significant impact on the electrical performances of the insulating oil, such as the dielectric loss factor, resistivity. So there is an important significance to investigate the influence of insulating oil by trace water, and monitor its operating status with effective measures. First, it is necessary to prepare the insulating oil samples with different water content and treat them 8 hours with ultrasonic oscillator, and observe microscopic images about the water-oil mixtures in order to study their relative uniformity and stable time, in the way it can be concluded that the relative uniformity can be kept favorable during the 25 min stable time for free water and emulsification water in oil; Based on this conclusion, the dielectric loss factor, resistivity were tested and the electrical performances of insulating oil with different water content in oil can obtained by analyzing these data; Then, the absorbance value of the different water content in oil at the spectral wave number of 1 640, 3 400, 3 450, 3 615 cm(-1), with the mid-infrared spectral scanning and analyzing to the different water content in oil, Therefore, combined the water absorbance values by the mid-infrared spectral scanning and analyzing with the experimental data of dielectric loss factor value, resistivity value of oil samples. The results shows that the absorbance value of the different water content in oil has a significant difference at the spectral wave number of 1 640, 3 400, 3450, 3 615 cm(-1), their correlation coefficient are 0.964 1, 0.984 8, 0.984 5, 0.944 0 between the absorbance value and water content at the spectral wave number of 1 640, 3 400, 3 450, 3 615 cm(-1), it can be obtained that the absorbance value of sample of moisture in the corresponding characteristic wave number can better reflect the change trend of water content; there is the highly relative of water absorbance values at the spectral wave number of 3 400 and 3 450 cm(-1) with the trends of oil dielectric loss factor values, their correlation coefficient are 0.860 6, 0.863 6; and relative of water absorbance values at the spectral wave number of 1 640 and 3 615 cm(-1) with the trends of oil resistivity values, their correlation coefficient is -0.931 5 and -0.968 0, this result can be lay the foundation research for monitoring the trace water in oil. PMID- 26904811 TI - [EEMD-ICA Applied in Signal Extraction in Functional Near-Infrared Spectroscopy]. AB - Currently, functional near-infrared spectroscopy (fNIRS) is widely used in the field of Neuroimaging. To solve the signal-noise frequency spectrum aliasing in non-linear and non-stationary fNIRS characteristic signal extraction, a new joint multi-resolution algorithm, EEMD-ICA, is proposed based on combining Independent Component Analysis with Ensemble Empirical Mode Decomposing. After functional brain imaging instrument detected the multi-channel and multi-wavelength NIR optical density signals, EEMD was performed to decompose measurement signals into multiple intrinsic mode function according to the signal frequency component. Then ICA was applied to extract the interest data from IMFs into ICs. Finally, reconstructed signals were obtained by accumulating the ICs set. EEMD-ICA was applied in de-noising Valsalva test signals which were considered as original signals and compared with Empirical Mode Decomposing and Ensemble Empirical Mode Decomposing to illustrate validity of this algorithm. It is proved that useful information loss during de-noising and invalidity of noise elimination are completely solved by EEMD-ICA. This algorithm is more optimized than other two de noising methods in error parameters and signal-noise-ratio analysis. PMID- 26904812 TI - [Application of NIR Spectroscopy for Nondestructive Qualitative and Quantitative Analysis of Lotus Seeds]. AB - By extracting the Near Infrared (NIR) diffuse reflectance spectral characteristics from the post-harvest lotus seeds in different storage periods, the quantitative and qualitative analysis were applied to lotus seeds with the Soluble Solids Content (SSC) and dry matter content (DM) as criteria. The results of the Partial Least Squares Regression (PLSR) and distance discrimination (DA) models showed that the absorption spectra of lotus seeds and lotus kernels has clear relations to their SSC and DM. The PLSR models of SSC and DM of lotus seeds had the best performance in 5 941-12 480 cm(-1) spectral region in this study. Their correlation coefficients of prediction were 0.74 and 0.82, and the correlation coefficients of calibration were 0.82 and 0.84, and the correlation coefficients of leave one out cross validation were 0.72 and 0.71. The PLSR model of SSC of lotus kernels was better in 7 891-9 310 cm(-1) spectral region. Its correlation coefficient of prediction was 0.79, and the correlation coefficient of calibration was 0.84, and the correlation coefficient of leave one out cross validation was 0.77. The PLSR model of DM of lotus kernels is better in the full spectral region. Its correlation coefficient of prediction was 0.92, and the correlation coefficient of calibration was 0.89, and the correlation coefficient of leave one out cross validation was 0.82. For lotus seeds, the DA model in 5 400-7 885 cm(-1) spectral region is the best with a correctness of 84.2%. And for lotus kernels, the DA model in 9 226-12 480 cm(-1) spectral region is the best with a correctness of 90.8%. For dry lotus kernels, the discriminant accuracy of the DA model is 98.9% in the optimal spectral region. All kernels with membrane and plumule were correctly discriminated. This research shows that the NIR spectroscopy technique can be used to determine SSC and DM content of lotus seeds and lotus kernels, as well as to discriminate their freshness and also to discriminate dry lotus kernels of different age and the kernels with membrane and plumule. PMID- 26904813 TI - [Rapid Quantitative Analysis of Content of the Additive in Gasoline for Motor Vehicles by Near-Infrared Spectroscopy]. AB - A new rapid quantitative method for the determination of oxygenates and the compounds not included in the national standard in gasoline using near-infrared spectroscopy is raised by this paper. This method combine near-infrared spectroscopy with oblique projection. This experiment choose four different types of gasoline, including reconcile gasoline, FCC refined gasoline, reformed gasoline and desulfurizing gasoline. Prepare series gasoline samples containing different concentrations and different types of compounds. Using FTIR spectrometer to measure those samples and got transmission spectrums. Oblique projection method could separate quantity spectral signal from mixed spectrum signal, and using projection to calculate and analyze the separated signal to obtain the content of measured component. The deviation between this method and the real content is low, the absolute error is less than 0.8 and the relative error is less than 8%. For the actual gasoline samples, compare results of this method with gas chromatography, the absolute error are less than 0.85 and the relative error are less than 6.85%. This method solves the problem of general multivariate calibration methods. It is very significant for the development of rapid detection technology using NIR suitable for on-site and the improvement of the quality of gasoline. PMID- 26904814 TI - [Rapid Identification of Epicarpium Citri Grandis via Infrared Spectroscopy and Fluorescence Spectrum Imaging Technology Combined with Neural Network]. AB - To explore rapid reliable methods for detection of Epicarpium citri grandis (ECG), the experiment using Fourier Transform Attenuated Total Reflection Infrared Spectroscopy (FTIR/ATR) and Fluorescence Spectrum Imaging Technology combined with Multilayer Perceptron (MLP) Neural Network pattern recognition, for the identification of ECG, and the two methods are compared. Infrared spectra and fluorescence spectral images of 118 samples, 81 ECG and 37 other kinds of ECG, are collected. According to the differences in tspectrum, the spectra data in the 550-1 800 cm(-1) wavenumber range and 400-720 nm wavelength are regarded as the study objects of discriminant analysis. Then principal component analysis (PCA) is applied to reduce the dimension of spectroscopic data of ECG and MLP Neural Network is used in combination to classify them. During the experiment were compared the effects of different methods of data preprocessing on the model: multiplicative scatter correction (MSC), standard normal variable correction (SNV), first-order derivative(FD), second-order derivative(SD) and Savitzky-Golay (SG). The results showed that: after the infrared spectra data via the Savitzky Golay (SG) pretreatment through the MLP Neural Network with the hidden layer function as sigmoid, we can get the best discrimination of ECG, the correct percent of training set and testing set are both 100%. Using fluorescence spectral imaging technology, corrected by the multiple scattering (MSC) results in the pretreatment is the most ideal. After data preprocessing, the three layers of the MLP Neural Network of the hidden layer function as sigmoid function can get 100% correct percent of training set and 96.7% correct percent of testing set. It was shown that the FTIR/ATR and fluorescent spectral imaging technology combined with MLP Neural Network can be used for the identification study of ECG and has the advantages of rapid, reliable effect. PMID- 26904815 TI - [Source Constraints on Turquoise of the Erlitou Site by Infrared Spectra]. AB - Shiyan district in Hubei province is a famous locality of high-quality turquoise with brightcolor, finegrain in the world. Erlitou archacologicalsite, which is about 300km north to the Shiyan Turquoise mine, has been excavated a remarkable number of turquoise artifacts since 2002. Some researchers infer that there was "a road of turquoise" between the two sites in history. In order to check the inference, and identify local features of the turquoises found in Shiyan, and Eelitou site as well, spectra of three turquoise groups from Shiyan, Hubei and one group of Erlitou unearthed samples were obtained by means of IR. Their spectra have visible differences in the 1 200-950 and 700-400 cm(-1) range. Peak 1 174 cm(-1) appears only in samples from Wenfeng, and from 700 to 400 cm(-1), 5 peaks show in samples from Wenfeng while 7 peaks emerge from the other two sites. Turquoises in Erlitou site have similar spectra to those from Qingu and Yungaisi, and are more similar to Yungaisi of peak around 1 159 cm(-1). According to A = lg(1/T) , intensity of transmittance spectra were calculated and then Ratios(A783 cm(-1)/A837 cm(-1)) were yielded. The ratios of samples from Qingu, Wenfeng, Yungaisi and Erlitou site are 0.819-0.920, 0.870-1.010, 0.806-0.860 and 0.827 0.878 respectively, allowing for a suggestion that turquoise in Erlitou site was the most probable from Yungaisi. This research can be used as example for identifying origin of the unearthed turquoise relics, which is more likely a good tool for archeological research. PMID- 26904816 TI - [Detection of Cinnabars in Mongolian Medicines Using Raman Spectroscopy]. AB - Cinnabar could soothe the nerves and the powder of cinnabar is always added in traditional Chinese medicine or mongolian medicines. The surface-enhanced Raman spectrum of cinnabar was identified using a portable Raman spectrometer and most structure vibration information was obtained. The results show that the Raman peaks of cinnabars were located at 253, 290, 343 cm(-1) and this three Raman characteristic peaks were selected for cinnabar identification. Meanwhile, the Raman spectra of several mongolian medicines were collected. The results showed that Raman signal of cinnabar could be observed in several mongolian medicines which contain cinnabar and Raman signal of cinnabar couldn't be detected in several mongolian medicines without cinnabar. In addition, the cinnabar in the oral ulcer powder was semi-quantitative analyzed and the limit of detection could reach to 10% of mass fraction. The relationship between the doped amount of cinnabar in the oral ulcer powder and the Raman intensity of characteristic peak was fitted and the correlation coefficient (r) was 0.995 9, which validated the accuracy of the result. This Raman analysis method for cinnabar detection is rapid, simple and accurate and it can be applied widely in mongolian medicines determination. PMID- 26904817 TI - [Red Blood Cells Raman Spectroscopy Comparison of Type Two Diabetes Patients and Rats]. AB - By using confocal Raman spectroscopy, Raman spectra were measured in normal rat red blood cells, normal human red blood cells, STZ induced diabetetic rats red blood cells, Alloxan induced diabetetic rats red blood cells and human type 2 diabetes red blood cells. Then principal component analysis (PCA) with support vector machine (SVM) classifier was used for data analysis, and then the distance between classes was used to judge the degree of close to two kinds of rat model with type 2 diabetes. The results found significant differences in the Raman spectra of red blood cell in diabetic and normal red blood cells. To diabetic red blood cells, the peak in the amide VI C=O deformation vibration band is obvious, and amide V N-H deformation vibration band spectral lines appear deviation. Belong to phospholipid fatty acyl C-C skeleton, the 1 130 cm(-1) spectral line is enhanced and the 1 088 cm(-1) spectral line is abated, which show diabetes red cell membrane permeability increased. Raman spectra of PCA combined with SVM can well separate 5 types of red blood cells. Classifier test results show that the classification accuracy is up to 100%. Through the class distance between the two induced method and human type 2 diabetes, it is found that STZ induced model is more close to human type 2 diabetes. In conclusion, Raman spectroscopy can be used for diagnosis of diabetes and rats STZ induced diabetes method is closer to human type 2 diabetes. PMID- 26904818 TI - [Simulated Experimental Research on Using Canopy Spectra of Surface Vegetation to Detect CO2 Microseepage Spots]. AB - With the global warming, people now pay more attention to the problem of the emission of greenhouse gas (CO2). Carbon capture and storage (CCS) technology is an effective measures to reduce CO2 emission. But there is a possible risk that the CO2 might leak from underground. However, there need to research and develop a technique to quickly monitor CO2 leaking spots above sequestration fields. The field experiment was performed in the Sutton Bonington campus of University of Nottingham (52. 8N, 1. 2W) from May to September in 2008. The experiment totally laid out 16 plots, grass (cv Long Ley) and beans (Vicia faba cv Clipper) were planted in eight plots, respectively. However, only four grass and bean plots were stressed by the CO2 leakage, and CO2 was always injected into the soil at a rate of 1 L x min(-1). The canopy spectra were measured using ASD instrument, and the grass was totally collected 6 times data and bean was totally collected 3 times data. This paper study the canopy spectral characteristics of grass and beans under the stress of CO2 microseepages through the field simulated experiment, and build the model to detect CO2 microseepage spots by using hyperspectral remote sensing. The results showed that the canopy spectral reflectance of grass and beans under the CO2 leakage stress increased in 580-680 nm with the stressed severity elevating, moreover, the spectral features of grass and beans had same rule during the whole experimental period. According to the canopy spectral features of two plants, a new index AREA(5800680 nm) was designed to detect the stressed vegetations. The index was tested through J-M distance, and the result suggested that the index was able to identify the center area and the core area grass under CO2 leakage stress, however, the index had a poor capability to discriminate the edge area grass from control. Then, the index had reliable and steady ability to identify beans under CO2 leakage stress. This result could provide theoretical basis and methods for detecting CO2 leakage spots using hyperspectral remote sensing in the future. PMID- 26904819 TI - [Measurements of CO2 Concentration Profile in Troposphere Based on Balloon-Borne TDLAS System]. AB - The main source and sink of CO2 in the atmosphere are concentrated in the troposphere. It is of great significance to the study of CO2 flux and global climate change to obtain the accurate tropospheric CO2 concentration profile. For the characteristics of high resolution, high sensitivity and fast response of tunable diode laser absorption spectroscopy (TDLAS), a compact balloon-borne system based on direct absorption was developed to detect the CO2 concentration profiles by use of the 2 004. 02 nm, R(16), v1+v3 line without the interfere of H2O absorption and the CO2 density of the number of molecules below 10 km in the troposphere was obtained. Due to the balloon-borne environment, a compact design of one single board integrated with laser driver, signal conditioning, spectra acquiring and concentration retrieving was developed. Limited by the working capability and hardware resources of embedded micro-processor, the spectra processing algorithm was optimized to reduce the time-cost. Compared with the traditional TDLAS sensors with WMS technique, this system was designed based on the direct absorption technique by means of an open-path Herriott cell with 20 m optical-path, which avoided the process of standardization and enhanced the environmental adaptation. The universal design of hardware and software platform achieved diverse gas measuring by changing the laser and adjusting some key parameters in algorithm. The concept of compact design helped to reduce the system's power and volume and balanced the response speed and measure precision. The power consumes below 1.5 W in room temperature and the volume of the single board is 120 mm x 100 mm x 25 mm, and the measurement accuracy is +/- 0.6 x 10( 6) at 1.5 s response time. It has been proved that the system can realize high precision detection of CO2 profile at 15 m vertical resolution in troposphere and TDLAS is an available method for balloon-borne detection. PMID- 26904820 TI - [Measurement of Trace C2H6 Based on Optical-Feedback Cavity-Enhanced Absorption Spectroscopy]. AB - Ethane is one of major fault characteristic gases dissolved in power transformer, the detection of Ethane with high accuracy and sensitivity is the key of dissolved gas analysis. In this paper, based on optical feedback theory and cavity-enhanced absorption spectroscopy, combined with quantum cascade laser, a detection system for dissolved gas C2 H6 in transformer oil was built up. Based on the symmetry of the individual cavity modes, the phase matching of returning light in resonance with the cavity was achieved through LabVIEW codes. The optical feedback effect that the emitted light return to the laser cavity after a small delay time and lock to the resonance frequency of cavity, even and odd modes effect that the higher modes and lower modes structure will build up alternatively, and threshold current lowering effect of about 1.2 mA were studied and achieved. By cavity ring-down spectroscopy, the effective reflectivity of 99.978% and cavity finesse of 7 138.4 is obtained respectively. The frequency selectivity is 0.005 2 cm(-1). With an acquisition time of 1s, this optical system allows detection for the PQ3 band of C2 H6 with high accuracy of 95.72% +/ 0.17% and detection limit of (1.97 +/- 0.06) x 10(-3) MUL x L(-1) at atmospheric pressure and temperature of 20 degrees C, which lays a foundation for fault diagnose from dissolved gas analysis. PMID- 26904821 TI - [Monitoring the Redox States of Thioredoxin in Protein-Protein Interaction Using Intrinsic Fluorescence Probe]. AB - The cellular redox states directly affect cell proliferation, differentiation and apoptosis, and the redox states changes is particularly important to the regulation of cell survival or death. Thioredoxin is a kind of oxidation regulatory protein which is widely exists in organisms, and the change of redox states is also an important process in redox regulation. In this work, we have used the site-directed mutagenesis of protein, SDS-polyacrylamide gel electrophoresis fluorescence spectroscopy and circular dichroism etc., to investigate redox states changes between TRX (E. coli) and glutathione peroxidase(GPX3) during their interaction. By observing the fluorescence spectra of TRX and its mutants, we have studied the protein interactions as well as the redox states switching between oxidation state TRX and the reduced state GPX3. The results demonstrate the presence of interactions and electron exchanges occurring between reduced GPX3 and oxidized TRX, which is of significance for revealing the physical and chemical mechanism of TRX in intracellular signal transduction. PMID- 26904822 TI - [Analysis of Observers Metamerism Differences for Different Retinal Cone Visual Responses]. AB - In order to investigate the cone's spectral responses under different conditions for different aged observers with normal color vision, nine color patches with different hue angles distributed uniformly on the CIELAB color space were prepared, and the 27-35 observers were organized to carry out color matching experiments on a monitor to match the nine printed color samples under four different viewing conditions including two illuminances, and two viewing fields. The spectral data obtained from the color matching experiments were compared with the spectral data of the nine target colors and used to test the performances of eleven color matching functions including CIE1931, CIE1964, CIE2006, Sarkar's S1 S8 in terms of the percentage of the minimum CIEDE2000 value. For the four experiments, CIE2006 and S6 performed the best and with S1, S2 the worst. For different observers, the visual spectral responses' of the retinal cone are different and the age has the obvious influence on the visual spectral responses. The observer metamerism is mainly caused by the different spectral response of the (A) channel and for most observers the differences appeared at the responses of the peak wavelength, and the shift of the peak wavelength has no significant influence on the observers metamerism. The experimental results can provide evidences for the classification of the color matching functions for different observer categories and theoretical basis for the investigation of the observers metamerism. PMID- 26904823 TI - [Preparation of delta-Valerolactone and Its Spectral Analysis]. AB - In the study, CuO/ZnO/Al2O3 was prepared by sol-gel method. Its catalytic activity was evaluated by gas-phase catalytic dehydrogenation of 1, 5-Pentanediol to delta-valerolactone as a probe reaction. CuO/ZnO/Al2O3 and long period reactive CuO/ZnO/Al2O3 were detected by XRD. Micro-structure and essence disciplinarian of CuO/ZnO/Al2O3 were disclosed. Metal ions had a cooperative effects during the catalytic dehydrogenation of 1, 5-pentanediol to delta valerolactone. After CuO/ZnO/Al2O3 deactivation, crystal particle size was increased clearly. It were found that characteristic diffraction peaks were caused by the catalyst temperature raising in methanol catalytic synthesis of ZnO. 1, 5-Pentanediol and delta-valerolactone were detected by FTIR. Their internal chemical bond and molecular structure were disclosed. The purity of delta-valerolactone product was very high. delta-Valerolactone and its polymer were detected by DSC. delta-Valerolactone possessed with poor stability. Polymerization reaction was easily happened by itself. So it was worth focusing on how to improve the stability of the delta-valerolactone monomer. This study could provide basic data and experimental basis for gas-phase catalytic dehydrogenation of 1, 5-Pentanediol to delta-valerolactone in pilot and industrial scale up research. PMID- 26904824 TI - [Road Extraction in Remote Sensing Images Based on Spectral and Edge Analysis]. AB - Roads are typically man-made objects in urban areas. Road extraction from high resolution images has important applications for urban planning and transportation development. However, due to the confusion of spectral characteristic, it is difficult to distinguish roads from other objects by merely using traditional classification methods that mainly depend on spectral information. Edge is an important feature for the identification of linear objects (e. g. , roads). The distribution patterns of edges vary greatly among different objects. It is crucial to merge edge statistical information into spectral ones. In this study, a new method that combines spectral information and edge statistical features has been proposed. First, edge detection is conducted by using self-adaptive mean-shift algorithm on the panchromatic band, which can greatly reduce pseudo-edges and noise effects. Then, edge statistical features are obtained from the edge statistical model, which measures the length and angle distribution of edges. Finally, by integrating the spectral and edge statistical features, SVM algorithm is used to classify the image and roads are ultimately extracted. A series of experiments are conducted and the results show that the overall accuracy of proposed method is 93% comparing with only 78% overall accuracy of the traditional. The results demonstrate that the proposed method is efficient and valuable for road extraction, especially on high-resolution images. PMID- 26904825 TI - [Research on the Spectrophotometry for Determination of Flavonoids in Waste Residue of Stevia Rebaudiana]. AB - A spectrophotometric method for the determination of flavonoids content in Waste Residue of Stevia Rebaudiana was established by comparing the UV-Vis spectra with three spectrophotometric methods: Direct, AlCl3 and NaNO2-Al (NO3)3-NaOH method. The effects of spectrophotometric reaction were studied by analyzing the wavelength, the dosage of color development reagent, reaction time, temperature and pH. The further research was studied by analyzing linearity between the absorbance and the concentration, the stability of this color system, the recovery rate and so on. The results showed that NaNO2-Al(NO3)3-NaOH method was best. The wavelength was 500 nm. The standard sample was rutin. There was a good linear relationship in the ranges of 2 - 24 MUg x mL(-1), correlation coefficient R2 = 0.999 5. The recovery of the additional sample was 96.0%-104.3%. The relative standard deviation(RSD) is respectively 3.75%. The dosages of NaNO2 and Al(NO3)3 both were 1.0 mL, both of their reaction time was 6 min. The dosage of NaOH was 15.0 mL and the reaction time was 15 min. The temperature in the whole process of the reaction must be maintained at 40 degrees C and pH is 5. The spectrophotometric condition was further improved on the determination of flavonoids content. This method, which is simple, rapid and accuracy, can be used in practical application. PMID- 26904826 TI - [Determination of Methyl Orange and Ethyl Orange in Two-Component Solution by Dual Wavelength Spectrophotometry]. AB - The high similarity of MO and EO made it difficult to measure concentration of MOD and EOD. In this paper, dual wavelength spectrophotometry was used to determinate the concentration of MOD and EOD, which was proved to be fast and accrate. 429.00 nm and 469.50 nm were selected as detemination wavelengthes at pH 12. And the influences of Na+ and Cl- on determination of MOD and EOD were surveyed. The standard equations were A429 = 0.003 47 + 0.061 cm + 0.056 46 C(E) and A469.50 = 0.002 8 + 0.074 37 cm + 0.083 94 c(E) . Recovery of standard additions of MOD and EOD were larger than 95%, and relative standard deviation of standard equations were less than 2%. The addition of NaCl has little effect on recovery of standard additions and relative standard deviation of this method. PMID- 26904827 TI - [The Study Based on Rectification of Vegetation Indices with Dust Impact]. AB - Vegetation indices are the simplest and most effective metric parameters representing the features of vegetation cover and growth condition. This paper used Euonymus japonicas Thunb as a study case and collected 200 leaf samples in 20 locations. Using electronic analytical balance and ASD hyperspectral radiometer with Win FOLIA leaf area meter obtained the data of the amount of dust, spectral information and leaf area. Through comparative analysis between dust and clean leaves, differences of spectral curve and vegetation indices were apparent. Then, combined with dust weight and spectral data, dust correction models-for vegetation indices were built. The analysis results showed that the spectral curve between clean and dust leaves have typical characteristics: blue edge and red edge were at 520 and 705 nm; however, dust influenced leaf reflectance significantly in range of 350-700, 750-1 350, 1 500-1 850, 1 900-2 100 nm wavelength, and had a greater impact on vegetation indices. With dust weight increasing, the linear correlation of dust with NDVI AND PRI was non significant, but that with NDWI, NDII and CAI was still significant. The verification of correction models showed that coefficient of determination (R2) of NDVI, NDII, CAI and PRI were 0.547, 0.430, 0.653 and 0.96 and their root mean square error (RMSE) was 0.035, 0.020, 0.112 and 0.009 respectively. Furthermore, it showed that applying dust correction models can improve the accuracy of vegetation indices calculation. PMID- 26904829 TI - [Spectral Uncertainty of Terrestrial Objects and the Applicability of Spectral Angle Mapper Algorithm]. AB - The spectral uncertainty of terrestrial objects causes a certain degree of spectral differences among feature spectra, which affects the accuracy of object recognition and also impacts the object recognition of spectral angle mapper algorithm (SAM). The spectral angle mapper algorithm is based on the overall similarity of the spectral curves, which was widely used in the classification of hyperspectral remotely sensed information. The spectral angle mapper algorithm does not take the spectral uncertainty of terrestrial objects into account while calculating the spectral angle between the spectral curves, and therefore does not tend to correctly identify the target objects. The applicability of the spectral angle mapper algorithm is studied for the spectral uncertainty of terrestrial objects and a modified SAM is proposed in this paper. In order to overcome the influence of the spectral uncertainty, the basic idea is to set a spectral difference value for the test spectra and the reference spectra and to calculate the spectral difference value based on derivation method according to the principle of minimum angle between the test spectra and the reference spectra. By considering the impact of the spectral uncertainty of terrestrial objects, this paper uses five kaolinite mineral spectra of USGS to calculate the spectral angle between the five kalinite mineral spectra by using local band combination and all bands to verify the improved algorithm. The calculation results and the applicability of the spectral angle mapper algorithm were analyzed. The results obtained from the experiments based on USGS mineral spectral data indicate that the modified SAM is not only helpful in characterizing and overcoming the impact of the spectral uncertainty but it can also improve the accuracy of object recognition to certain extent especially for selecting local band combination and has better applicability for the spectral uncertainty of terrestrial objects. PMID- 26904828 TI - [Plant Spectral Discrimination Based on Phenological Features]. AB - Spectral analysis plays a significant role onplant characteristic identification and mechanism recognition, there were many papers published on the aspects of absorption features in the spectra of chlorophyll and moisture, spectral analysis onvegetation red edge effect, spectra profile feature extraction, spectra profile conversion, vegetation leaf structure and chemical composition impacts on the spectra in past years. However, fewer researches issued on spectral changes caused by plant seasonal changes of life form, chlorophyll, leaf area index. This paper studied on spectral observation of 11 plants of various life form, plant leaf structure and its size, phenological characteristics, they include deciduous forest with broad vertical leaf, needle leaf evergreen forest, needle leaf deciduous forest, deciduous forest with broadflat leaf, high shrub with big leaf, high shrub with little leaf, deciduous forest with broad little leaf, short shrub, meadow, steppe and grass. Field spectral data were observed with SVC-HR768 (Spectra Vista company, USA), the band width covers 350-2 500 nm, spectral resolution reaches 1-4 nm. The features of NDVI, spectral maximum absorption depth in green band, and spectral maximum absorption depth in red band were measured after continuum removal processing, the mean, amplitude and gradient of these features on seasonal change profile were analyzed, meanwhile, separability research on plant spectral feature of growth period and maturation period were compared. The paper presents a calculation method of separability of vegetation spectra which consider feature spatial distances. This index is carried on analysis of the vegetation discrimination. The results show that: the spectral features during plant growth period are easier to distinguish than them during maturation period. With the same features comparison, plant separability of growth period is 3 points higher than it during maturation period. The overall separabilityof vegetation spectrum features shows seasonal amplitude > seasonal gradient > seasonal mean during the growth period, but the separability of seasonal gradient shows highest value for the plant seasonal NDVI change. Therefore, the features of seasonal NDVI gradient, seasonal amplitude of maximumspectral absorption depth in green band, seasonal amplitude of maximumabsorption depthin red band are effective composition for plant discrimination. PMID- 26904830 TI - [A Hyperspectral Imagery Anomaly Detection Algorithm Based on Gauss-Markov Model]. AB - With the development of spectral imaging technology, hyperspectral anomaly detection is getting more and more widely used in remote sensing imagery processing. The traditional RX anomaly detection algorithm neglects spatial correlation of images. Besides, it does not validly reduce the data dimension, which costs too much processing time and shows low validity on hyperspectral data. The hyperspectral images follow Gauss-Markov Random Field (GMRF) in space and spectral dimensions. The inverse matrix of covariance matrix is able to be directly calculated by building the Gauss-Markov parameters, which avoids the huge calculation of hyperspectral data. This paper proposes an improved RX anomaly detection algorithm based on three-dimensional GMRF. The hyperspectral imagery data is simulated with GMRF model, and the GMRF parameters are estimated with the Approximated Maximum Likelihood method. The detection operator is constructed with GMRF estimation parameters. The detecting pixel is considered as the centre in a local optimization window, which calls GMRF detecting window. The abnormal degree is calculated with mean vector and covariance inverse matrix, and the mean vector and covariance inverse matrix are calculated within the window. The image is detected pixel by pixel with the moving of GMRF window. The traditional RX detection algorithm, the regional hypothesis detection algorithm based on GMRF and the algorithm proposed in this paper are simulated with AVIRIS hyperspectral data. Simulation results show that the proposed anomaly detection method is able to improve the detection efficiency and reduce false alarm rate. We get the operation time statistics of the three algorithms in the same computer environment. The results show that the proposed algorithm improves the operation time by 45.2%, which shows good computing efficiency. PMID- 26904831 TI - [Hyperspectral Remote Sensing Estimation Models for Pasture Quality]. AB - Crude protein (CP), crude fat (CFA) and crude fiber (CFI) are key indicators for evaluation of the quality and feeding value of pasture. Hence, identification of these biological contents is an essential practice for animal husbandry. As current approaches to pasture quality estimation are time-consuming and costly, and even generate hazardous waste, a real-time and non-destructive method is therefore developed in this study using pasture canopy hyperspectral data. A field campaign was carried out in August 2013 around Qinghai Lake in order to obtain field spectral properties of 19 types of natural pasture using the ASD Field Spec 3, a field spectrometer that works in the optical region (350-2 500 nm) of the electromagnetic spectrum. In additional to the spectral data, pasture samples were also collected from the field and examined in laboratory to measure the relative concentration of CP (%), CFA (%) and CFI (%). After spectral denoising and smoothing, the relationship of pasture quality parameters with the reflectance spectrum, the first derivatives of reflectance (FDR), band ratio and the wavelet coefficients (WCs) was analyzed respectively. The concentration of CP, CFA and CFI of pasture was found closely correlated with FDR with wavebands centered at 424, 1 668, and 918 nm as well as with the low-scale (scale = 2, 4) Morlet, Coiflets and Gassian WCs. Accordingly, the linear, exponential, and polynomial equations between each pasture variable and FDR or WCs were developed. Validation of the developed equations indicated that the polynomial model with an independent variable of Coiflets WCs (scale = 4, wavelength =1 209 nm), the polynomial model with an independent variable of FDR, and the exponential model with an independent variable of FDR were the optimal model for prediction of concentration of CP, CFA and CFI of pasture, respectively. The R2 of the pasture quality estimation models was between 0.646 and 0.762 at the 0.01 significance level. Results suggest that the first derivatives or the wavelet coefficients of hyperspectral reflectance in visible and near-infrared regions can be used for pasture quality estimation, and that it will provide a basis for real-time prediction of pasture quality using remote sensing techniques. PMID- 26904832 TI - [Study on the Relationship between Hyperspectral Polarized Information of Soil Salinization and Soil Line]. AB - It has important significance to assess soil salinization correctly for agricultural production and ecological environment. Soil line can indicate soil salinization in a certain extent. But the soil spectral characteristics obtained at different angles will change with the changing of the soil line parameters. Base on polarized hyper-spectral reflectivity obtained in the laboratory, the study analyzes the relationship between the soil salinization and soil line parameters, explores preliminarily the best way to obtain soil line. The results show: (1) Soil spectral reflectance gradually increased slowly with increasing band. With the enhanced level of salinization, soil spectral reflectance of the first to be gradually reduced to a critical value and then gradually increased. (2) Soil salinization has a linear correlation with the soil slope and intercept. With the enhanced level of salinization, soil slope becomes smaller, and intercept becomes larger. (3) Viewing zenith angle affects the relationship between the polarization state and soil line parameters. When viewing zenith angle is fixed, there is a regularity between the polarization state and soil line parameters. When the viewing zenith angle is between 0 degrees-50 degrees, with the angle becoming larger, soil slope becomes larger, and intercept becomes smaller. (4) Polarization states affects degree of correlation between soil salinization and soil line parameters. When polarization angle is 90 degrees and viewing zenith angle is 25 degrees, the relationship model between soil salinization and soil line parameters is better. The research results can be used to evaluate the degree of salinization soil. PMID- 26904833 TI - [Method of Remote Sensing Identification for Mineral Types Based on Multiple Spectral Characteristic Parameters Matching]. AB - The traditional mineral mapping methods with remote sensing data, based on spectral reflectance matching techniques, shows low accuracy, for obviously being affected by the image quality, atmospheric and other factors. A new mineral mapping method based on multiple types of spectral characteristic parameters is presented in this paper. Various spectral characteristic parameters are used together to enhanced the stability in the situation of atmosphere and environment background affecting. AVIRIS (Airborne Visible Infrared Imaging Spectrometer) data of Nevada Cuprite are selected to determine the mineral types with this method. Typical mineral spectral data are also obtained from USGS (United States Geological Survey) spectral library to calculate the spectral characteristic parameters. A mineral identification model based on multiple spectral characteristic parameters is built by analyzing the various characteristic parameters, and is applied in the mineral mapping experiment in Cuprite area. The mineral mapping result produced by Clark et al. in 1995 is used to evaluate the effect of this method, results show, that mineral mapping results with this method can obtain a high precision, the overall mineral identification accuracy is 78.96%. PMID- 26904834 TI - [Determination the Change of Main Trace Elements in the Ovary with Self- and Cross-Pollination of Chinese Chestnut by ICP-MS]. AB - Castanea mollissima Blume has potential as an non-wood forest trees that have been cultivated for thousands of years in China. In order to elucidate the trace elements of chestnut ovary, the major trace elements of self- and cross pollination chestnut ovary were determined by inductively coupled plasma mass spectrometry. The results showed that self- and cross-pollination 5-50 d, six trace elements trends showed fluctuations. After cross-pollination 20 d, the content of Ca was up to 6.50 mg x g(-1), while the self-pollination 10 d, the content of Ca reached up to 7.77 mg x g(-1). After cross- and self-pollination pollination 30 d, the content of Mg were highest, 4.19 and 4.69 mg x g(-1), respectively. After cross-pollination 5 d, the content of Zn reached the highest, 0.038 7 mg x g(-1), while self-pollination 10d the content of Zn was 0.039 9 mg x g(-1). After self- and cross-pollination 35 d, the content of Fe were 0.022, 0.019 mg x g(-1), respectively. After cross- and self-pollination 20 d, the content of Cu were 0.056, 0.045 mg x g(-1), respectively. After self-pollination 40d, the content of Mn reaching the highest was 1.204 mg x g(-1), while cross pollination 30 d, the content of Mn reached its maximum 0.845 mg x g(-1). The results can provide a reference for spraying fertilizer on the ovary development, thereby improving chestnut production. PMID- 26904835 TI - [Research on the Content Characteristics and Pollution Evaluation of Heavy Metals in Filtered Water and Suspended Particles from Gansu, Ningxia and Inner Mongolia Sections of the Yellow River in Wet Season Using HR-ICP-MS]. AB - The content characteristics, pollution evaluation and source identification of 6 heavy Metals (Cd, Pb, Cr, As, Cu and Zn) in filtered water and 9 heavy Metals (Cd, Pb, Cr, Ni, Cu, V, Co, Zn and Mn) in suspended particles from 10 sampling sites such as Zhaojunfuqiao (S1) and Baotoufuqiao (S2), etc. from Gansu, Ningxia and Inner Mongolia sections of the Yellow River in 2012 Wet Season were studied to understand the condition of the heavy metal pollution in Gansu, Ningxia and Inner Mongolia Sections of the Yellow River by using high resolution inductively coupled plasma-mass spectrometry (HR-ICP-MS). Multivariate geochemical approaches and statistical analysis were also exploited for assessing the level of heavy metals in filtered water and suspended particles from studied area. The results showed that in filtering water, only the concentrations of Cr exceeded the standard value of Environmental Quality Standard for Surface Water (GB3838-2002) and were the highest (74.8-94.7 MUg x L(-1)) among all elements in 10 sampling sites; Single factor pollution index (I(i)) results suggested that the water quality in all sampling sites were contaminated by both Cr and total nitrogen (TN), with the exception of TN in Baotoufuqiao (S2); Integrated Nemerow pollution index (I) indicated that the I values in all sampling sites were between 1-2 (light pollution), which implied that the water quality in Gansu, Ningxia and Inner Mongolia sections, especially downstream sections (S1-S6) of the Yellow River wasn't an ideal source for drinking and using in aquaculture any more. In suspended particles, concentrations of heavy metals were relatively higher than their soil background values in 10 sampling sites, except Ni in S10 (34.7 MUg x L(-1)). Index of geo-accumulation (I(geo)) indicated that the I(geo) values of Pb, Cr, Ni, Cu, V, Co, Zn and Mn in all sampling sites were less than 1 (unpolluted or unpolluted-moderately polluted), respectively, while I(geo)Cd were the highest in 10 sampling sites among all heavy metals and with the moderately to strong contamination in Zhaojunfuqiao (S1), Baotoufuqiao (S2), Wuhai (S5) and Dongdagouruhuanghekou (S8). The results of this paper would help to supply reliable experimental data for researching of distribution, migration and effective protection of heavy metals in study area. PMID- 26904836 TI - [Direct Determination of Heavy Metal Elements in Propolis by Inductively Coupled Plasma Mass Spectrometry]. AB - In current study, a method was established for simultaneous quantitative analysis of Cr, Ni, As, Cd, Sb, Sn, Hg and Pb in propolis by using inductively coupled plasma mass spectrometry. Before analyzed by ICP-MS, the propolis was diluted with n-propanol/xylene (70 : 30, phi). Organic sample can remain stable by diluting with n-propanol/xylene, result from long-time sample dispersion in the solution. Carbon accumulation on the sampling cone, which comes from the high carbon content of butter, will clog the orifice and decrease analysis sensitivity. Thus a small amount of oxygen was added into the argon gas line to eliminate carbon. ORS was used to eliminate the polyatomic interferences caused by the high salty matrixes. The effects of the He collision gas flow rate on estimating detection limits of Cr, Ni and As were investigated. The matrix effects and the instrument drift have been calibrated with Rh as internal standard element. The results show that the detection limits is in the range of 20.8-102.7 ng x L(-1), the recovery is in the range of 92.0%-109.0%, and the RSD is less than 3.5%. This method was simple, sensitive and precise to simultaneously analyze 8 heavy metal elements in propolis. PMID- 26904837 TI - [Analysis of Trace Inorganic Elements in Castor Oil by Inductively Coupled Plasma Mass Spectrometry]. AB - A method for the determination of Na, Mg, Si, P, K, Ca, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Sr, Mo, Cd, Hg and Pb in castor oil after direct dilution with ethanol by inductively coupled plasma mass spectrometry (ICP-MS) was established. The sample was diluted by ethanol before ICP-MS determination. The condensation and deposition of high concentrations of carbon in mass cone interface and ion lens, which will decrease the sensitivity of element analysis, were avoided effectively by introducing O2 to plasma. The mass spectral interferences were eliminated by octopole reaction system (ORS). The matrix effects were calibrated to using Sc, Ge, Rh and Ir as internal standard elements. Au standard solution, which could form amalgam alloy with Hg, was dropped to eliminate the memory effect of Hg. The results show that the correlation coefficient for analyte is no less than 0.999 5, the detection limits is in the range of 0.06 - 20.1 ng x L( 1), the recovery is in the range of 990.4% - 110.2%, and the RSD is less than 4.8%. This method was very fast, simple and accurate to simultaneously analyze multi-elements in castor oil. PMID- 26904838 TI - [Pretreatment of Aluminum-Lithium Alloy Sample and Determination of Argentum and Lithium by Spectral Analysis]. AB - Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES), Flame Atomic Absorption Spectrometry (FAAS) and Visible Spectrometry (VS) was applied for determination of Ag and Li in lithium-aluminium alloy standard sample and test sample, their respective advantages and disadvantages were compared, the excellent selectivity of ICP-OES was confirmed by analyses of certified standard sample. Three different sample digestion methods were compared and discussed in this study. It was found that the better accuracy would be obtained by digesting sample with chloroazotic acid while the content of Li was measured by FAAS, and it was better to digest sample with hydrochloric acid and hydrogen peroxide while determining Ag and Li by ICP-OES simultaneously and determining Ag by FAAS and VS. The interference of co-existing elements and elimination methods was detailedly discussed. Ammonium hydroxide was added to adjust the sample solution into alkalescent and Al, Ti, Zr was precipitated by forming hydroxide precipitation, Mg and Cu was formed complex precipitation with 8-hydroxyquinoline in this condition, then the interference from matrix element to determinate Ag by FAAS was eliminated. In addition, phosphate was used to precipitate Ti to eliminate its interference for determination of Li by FAAS. The same treatment of determination for Ag by FAAS was used to eliminate the interference of matrix element for determination of Ag by VS, the excess of nitrate was added into sample and heated to release Ag+ from silver chloride complex, and the color of 8 hydroxyquinoline was eliminated because of decomposed by heating. The accuracy of analysis result for standard sample was conspicuously improved which confirms the efficient of the method to eliminate interference in this study. The optimal digestion method and eliminate interference method was applied to lithium aluminium alloy samples. The recovery of samples was from 100.39% to 103.01% by ICP-OES determination for Ag, and from 100.42% to 103.01% by ICP-OES determination for Li. The recovery ranged from 95.91% to 99.98% by FAAS determination for Ag, and ranged from 98.04% to 99.98% for FAAS determination of Li. The recovery was from 98.00% to 101.00 by VS determination for Ag, the analysis results all meet the analysis requirement. PMID- 26904839 TI - [Analyse Output Specurum in Miniature Transmission X-Ray Tube of Aluminum Window and Silver Target by MC Simulation]. AB - The miniature transmission X-ray tube is widely used in energy dispersive X-ray Fluorescence Analysis (EDXRFA). The miniature transmission X-ray tube with a small, low power consumption, X-ray emission efficiency that can be made the excitation source of handheld X-ray energy dispersive fluorescence analyzer. Beryllium (Be) is the most commonly used X-ray window material. But beryllium is expensive and toxic. At the same time set filtering window by aluminum (Al) to reducing low-energy scattering rays. This paper be adopted Al for exit window material of miniature transmission X-ray tube, achieve high-energy rays transmission and low-energy scattered radiation shielding, at the same time reduce production cost and difficulty. The present paper simulate the X-ray tube output spectrum of silver (Ag) target and aluminum window with different thickness by MCNP5. We consider the X-ray of low energy part is completely shielded when aluminum windows thickness is greater than 1.5 mm. We can conclude that 2 MUm and 0.8 mm are the best combination of target thickness and aluminum windows through comparative analysis of existing research results. Then we can get flux of high energy part is big and low energy part is small when the target is 2 MUm thick Ag and the window is 0.8 mm thick Al. PMID- 26904840 TI - [Analysis of the Decorated Silicate Beads Excavated from Tomb M4 of the Ma-Jia Yuan Warring States Cemetery, Gansu Province]. AB - This paper reports the analysis results of 11 decorated silicate beads samples excavated from Ma Jia-yuan Warring State Cemetery, Gan Su Province with the portable X-ray fluorescence spectrometer, laser Raman spectrometer and X-ray diffraction spectrometer. It is includes 3 types among these samples on the basis of their chemical composition, NaO-CaO-SiO2, PbO-BaO-SiO2 glass system, and glassy faience. The blue part of the NaO-CaO-SiO2 glass sample was colored by Co2+, and Sb2O5 was discovered as opacifier. The results of Laser Raman analysis shows in some circle beads exits Chinese blue and Chinese purple. Combined with the existing research results the early cultural factors and technical exchange reflected from these samples are discussed. It shows that the material and craftsmanship of the beads contained Chinese blue and Chinese purple were affected by Qin Culture. But the composition of the Na-Ca-SiO2 glass eye bead is similar with those excavated from Xin Jiang area. It infers the technology of glass manufacture of the Xi Ron nationality was influenced by the Qin Culture and the grassland nationalities' culture simultaneously. The faience bead composed with the inner core and the outer glassy layer is possible a kind of transitional type between the faience and the real glass. This information offers a new reference for the research of the origin of the glass technology in the ancient China. PMID- 26904841 TI - [Species Determination and Spectral Characteristics of Swelling Clay Minerals in the Pliocene Sandstones in Xinghai, Qinghai]. AB - X-ray diffraction (XRD) and Fourier infrared absorption spectroscopy (FTIR) were conducted to deepen our research on specific species and spectral characteristics of swelling clay minerals in the Pliocene sandstones in Xinghai, Qinghai province. XRD results show that swelling clay minerals are dominant clay minerals in the sandstones, which can be up to 97% in percentage. XRD patterns show 060 reflections of the samples occur both remarkably at 1.534 A and 1.498 A, indicating the samples contain physical mixtures of trioctahedral and dioctahedral swelling clay minerals, respectively. Further treatment of Li-300 degrees C heat and glycerol saturation shows the swelling clay minerals collapse to 9.3-9.9 A with a partial expansion to -18 A. This indicates the swelling clay minerals dominate montmorillonite and contain minor saponite. The montmorillonite shows no swelling after Li-300 degrees C heat and glycerol saturation because of Li+ inserting into the octahedral layers, which balances the layer charge caused by the substitution of Mg to Al. FTIR results show the samples are composed of a kind of phyllosilicate with absorbed and structural water, which is in agreement with the results of XRD. Absorbed peaks at 913, 842, 880 cm(-1), corresponding to OH associated with Al-Al, Al-Mg, and Al-Fe pairs, further indicates the minerals are dominant dioctahedron in structure. Meanwhile, absorbed peaks at 625 and 519 cm(-1), corresponding to coupled Si-O and Al-O-Si deformation, indicates parts of Si is replaced by Al in tetrahedron. The spectral characteristics of the samples are against the presence of beidellite and nontronite based on the results of XRD and FTIR, while demonstrating an,existence of montmorillonite. This study, to distinguish the specific species of swelling clay species in clay minerals, would be of great importance when using clay mineralogy to interpret provenance and climatic information. PMID- 26904842 TI - [Research on New Type of Spectral Modulation Polarization Measurement Technology]. AB - Spectral Modulation Polarization Measurement technology (SMPM) is a new type of polarization modulation technology, with an achromatic /4 retarder, a multiple order retarder and a polarizer the polarization information of incident light can be encoded into the spectral dimension, sinusoidal which amplitude scales with the degree of the linear polarization and phase scales with the angle of the linear polarization can be acquired directly. With a dedicated algorithm for the modulated spectrum, we can get degree and angle of the linear polarization, spectral information and radiation information of the target. This paper expounds the basic principle of SMPM and concrete implementation scheme is proposed. Demodulation algorithm is designed before experimental platform are set up. Experiment which verified the correctness on the SMPM has carried on. The experimental results show the correctness and feasibility of SMPM. Compared with traditional polarization modulate techniques no moving parts and electronic components are including in this scheme. It's also has the advantages of compact and low mass. We can get all the polarization information through one single measurement rather than get Stokes parameters for further calculations. This study provides a new kind of technological approaches for the development of new space polarization detecting sensor. PMID- 26904843 TI - [A Time-Spatial Resolvable High Speed Spectrograph and Its Application on Spectrum Measurement of a Nanosecond Pulsed Underwater Spark Discharge]. AB - Recently, the diagnosis of the characteristic of pulsed underwater electrical discharges plasma have received significant attention. The measurement of a time spatial resolved spectrum emitted from a single discharge pulse is important for understanding the time-spatial evolution characteristics of plasma generated by a pulsed high-voltage discharge in water. In this paper, a high speed time-spatial resolvable spectrograph for measuring the emission spectrum of a single electrical discharge pulse was reported. The high speed time-spatial resolvable spectrograph has been constructed by combining an ultrahigh-speed frame camera system with monochromator. Software for the spectral analyzing was also developed. The performance of the spectrograph was tested by using a 632.8 nm He Ne laser beam at a 1 200 g x mm(-1) grating. The pixel resolution for 632.8 nm spectra is 0.013 nm. The instrument broadening for 632.8 nm spectra is (0.150 +/- 0.009)nm when the exposure.time of the camera is 20 ns and the width of entrance slit is 0.2 mm, and increases with increasing the slit width. The change of exposure time of the camera has no influence on the instrument broadening, ensuring the spectrograph in a steady performance while adjusting the exposure time of the camera. With the spectrograph, time-spatial resolved spectra emitted from a single discharge pulse of an underwater nanoseconds spark discharge were obtained. It provides good data for investigating the time-spatial evolution characteristics of the discharge plasma during a single discharge pulse. The spectrograph developed in this work provides a technical approach for studying the time-spatial evolution characteristic of, plasma generated by a single electrical discharge pulse. PMID- 26904844 TI - [A Brillouin Scattering Spectrum Feature Extraction Based on Flies Optimization Algorithm with Adaptive Mutation and Generalized Regression Neural Network]. AB - According to the high precision extracting characteristics of scattering spectrum in Brillouin optical time domain reflection optical fiber sensing system, this paper proposes a new algorithm based on flies optimization algorithm with adaptive mutation and generalized regression neural network. The method takes advantages of the generalized regression neural network which has the ability of the approximation ability, learning speed and generalization of the model. Moreover, by using the strong search ability of flies optimization algorithm with adaptive mutation, it can enhance the learning ability of the neural network. Thus the fitting degree of Brillouin scattering spectrum and the extraction accuracy of frequency shift is improved. Model of actual Brillouin spectrum are constructed by Gaussian white noise on theoretical spectrum, whose center frequency is 11.213 GHz and the linewidths are 40-50, 30-60 and 20-70 MHz, respectively. Comparing the algorithm with the Levenberg-Marquardt fitting method based on finite element analysis, hybrid algorithm particle swarm optimization, Levenberg-Marquardt and the least square method, the maximum frequency shift error of the new algorithm is 0.4 MHz, the fitting degree is 0.991 2 and the root mean square error is 0.024 1. The simulation results show that the proposed algorithm has good fitting degree and minimum absolute error. Therefore, the algorithm can be used on distributed optical fiber sensing system based on Brillouin optical time domain reflection, which can improve the fitting of Brillouin scattering spectrum and the precision of frequency shift extraction effectively. PMID- 26904845 TI - [Identification of Metoprolol Tartrate Tablets from Different Manufacturers by Different Near Infrared Spectrometers]. AB - To rapidly identify Metoprolol Tartrate tablets from different manufacturers, a qualitative analysis model can be established by near infrared spectroscopy. Firstly, AntarisII Fourier-transform near infrared (FT-NIR) spectroscopy and Micro NIR1700 Spectrometer were used to collect spectral data of 66 batches of samples which come from four different manufacturers, then 44 samples of calibration set and 22 samples of validation set were acquired by random sampling. In order to build up a PLS-DA model, the first derivative with Savitzky Golay 15 points smoothing (1d+SG15) and standard normal vitiate transformation (SNV) was selected as the pretreatment method and according to the variation between different samples and the characteristic absorption band, 6 468-7 104 cm( 1) and 6 468-7 156 cm(-1) were chosen as the modeling spectra region. The confusion matrix indicated that Metoprolol Tartrate tablets could be rapidly and effectively identified by two analytical models, which were established using the spectral data collected from two instruments. For these two models, both of the sensitivity and specificity were 100%. This study confirmed that it is feasible to carry out the manufacturer identification of Metoprolol Tartrate tablets by near infrared spectroscopy. Besides, the use of Micro NIR1700 Spectrometer, which is the minimum and portable near infrared spectrometer, provides valuable insights for fast on-site drug screening. PMID- 26904846 TI - Applying Attenuated Total Reflection-Mid-Infrared (ATR-MIR) Spectroscopy to Detect Hairtail Surimi in Mixed Surimi and Their Surimi Products. AB - ATR-MIR spectroscopic analysis was used to classify sliver carp surimi and surimi products adulterated with different levels of hairtail surimi. Five chemometric methods, including SIMCA (soft independent modeling class of analogies), KNN (K nearest neighbor), SVR (support vector machines regression), PLSDA (partial least squares discriminate analysis) and ID3 (interative dicremiser version 3) Decision tree were used to build the classifying models. And the performances of the models were compared. Results showed that for both cooked and uncooked mixed surimi samples, better classifications were obtained using SIMCA model, the percentage of the correct classification reached 96.59% and 96.43%, and the corresponding RMSECV were 0.185 7 and 0.189 8, r value were 0.988 0 and 0.994 1 respectively. The results of this study demonstrated for the first time that ATR MIR spectroscopy combined with chemometrics method can be used to classify sliver carp surimi and surimi products adulterated with different levels of hairtail surimi. PMID- 26904847 TI - Assessment of the Fluorescence Spectra Characteristics of Dissolved Organic Matter Derived from Organic Waste Composting Based on Projection Pursuit Classification (PPC). AB - The characteristics of fluorescence spectra of dissolved organic matter (DOM) derived from composting is one of the key ways to assess the compost maturity. However, the existing methods mainly focus on the qualitative description for the humification degree of compost. In this paper, projection pursuit classification (PPC) was conducted to quantitative assess the grades of compost maturity, based on the characteristics of fluorescence spectra of DOM. Eight organic wastes (chicken manure, swine manure, kitchen waste, lawn waste, fruits and vegetables waste, straw, green waste, and municipal solid waste) composting were conducted, the germination percentage (GI) and fluorescence spectra of DOM were measured during composting. Statistic analysis with all fluorescence parameters of DOM indicated that I436/I383 (a ratio between the fluorescence intensities at 436 and 383 nm in excitation spectra), FLR (an area ratio between fulvic-like region from 308 to 363 nm and total region in emission spectra), P(HA/Pro) (a regional integration ratio between humic acid-like region to protein-like region in excitation emission matrix (EEM) spectra), A4/A1 (an area ratio of the last quarter to the first quarter in emission spectra), r(A,C) (a ratio between the fluorescence intensities of peak A and peak C in EEM spectra) were correlated with each other (p < 0.01), suggesting that this fluorescence parameters could be considered as comprehensive evaluation index system of PPC. Subsequently, the four degrades of compost maturity included the best degree of maturity (I, GI > 80%), better degree of compost maturity (II, 60% < GI < 80%), maturity (III, 50% < GI < 60%), and immaturity (IV, GI < 50%) were divided according the GI value during composting. The corresponding fluorescence parameter values were calculated at each degrade of compost maturity. Then the projection values were calculated based on PPC considering the above fluorescence parameter values. The projection value was 2.01 - 2.22 for I grade, 1.21 - 2.0 for II grade, 0.57 - 1.2 for III grade, and 0.10 - 0.56 for IV grade. Model validation was then carried out with composts samples, the results indicated that the simulated values were agreed with the observed values, and the accuracy of PPC was 75% for four grades of maturity, and 100% for maturity and immaturity, suggesting that PPC could meet the need of the assessment of compost maturity. PMID- 26904848 TI - Terahertz Spectroscopy of Biotin and Pyridoxine. AB - Terahertz (THz) absorption spectra of the biotin and pyridoxine were studied using Fourier transform infrared spectroscopy (FTIR) at room temperature. These spectra exhibit enhanced absorption in THz range because of strong intramolecular and intermolecular vibration modes. In the experiment, the samples were mixed with high density polyethylene powder, which was used as spectrophotometric grid. The absorption spectra show worse consistency at higher frequencies for the high ratio of the samples to polyethylene. It indicates that the absorbance of the biotin and pyridoxine increased with frequency. Molecular vibrational spectral calculations based on density functional theory (DFT) show strong correlation with the experiment. We investigated the absorption spectra of isolated molecules (single molecule, two molecules, three molecules) and unit cell of crystal to clarify the mechanism of the spectra change due to intramolecular and intermolecular vibration and rotation. PMID- 26904849 TI - Preparation and SERS Study of Silver Microstructures with Dendritic Shape. AB - In the surface ehanced Raman scattering (SERS) technology, not only to improve the making process of SERS substrates, to be fast and easily, but also to enhance the SERS enhance factor, an easy replacement reaction between zinc and silver nitrate solution has been adopted to prepare silver micro-structures SERS-active substrate. The silver micro-substrates have many advantages. These substrates have good stability, well preservation, an easy making method and a fast making process. The surface profile of the silver microparticles is investigated by scanning electron microscope (SEM). The silver microstructures are dendritic shape in a symmetrical fashion with symmetrical distribution. When the time of the replace reaction is 40, 50 and 60 s, respectively, the average lengths of "trunks" in the silver dendritic microsubstractes are about 3, 5 and 10 MUm, and the lengths of the "branches" are about 700 nm, 2 MUm and 3 MUm, respectively. The result shows that the longer time the replacement reaction takes, the longer lengths of the "trunks" and "branches" in the silver dendritic microsubstractes become. With the time of replace reaction increasing, the "trunk" and "branch" in the silver dendritic microsubstractes grow longer and a large amount of nano level "leaves" grow out from the "branches" of the silver dendritic microsubstractes, so the silver micro size dendrates have nano level structure on surface. In order to investigate the SERS-active substrates application in SERS, a Fourier transform Raman spectrograph with a 1 064 nm laser wavelength is used to measure the SERS spectra. And good SERS spectra have been obtained by using dendritic silver microsubstrates on the silicon chip as a SERS substract, and Rhodamine 6G (R6G) as a molecule probe. It is found that the silver micro substrates have good Raman characteristics. And comparing these SERS spectra, it gets the conclution that the spectra with best SERS enhance effect are obtained when R6G is obsorbed on the silver dendritic micro-substractes whose preparing time is 40s, and at that time, the analytical enhancement factor for SERS signals is approximately 10(3). And when the silicon ships are dealed with surfactants Polyvinylpyrrolidone (PVP) and keeping the other conditions the same as before, the SERS enhance effect of the spectra becomes better, and the enhancement factor turn to be approximately 10(4). What's more, the silver microstructures can be preserved several monthes under deionized water and the repeatment of the expriment result is well in general. PMID- 26904850 TI - Synthesis, Growth and Spectroscopic Studies of Piperazinium Paranitrophenolate Monohydrate Crystals. AB - A new piperazinium 4-nitro phenolate monhydrate single crystal (PNP) was grown by employing the solution growth technique piperazine and 4-nitrophenol, were the source material used for the growth, acetonitrile is used as solvent. The grown crystal was characterized by Single X-ray analysis and it shows that piperazinium 4-nitrophenol monohydrate crystallizes in the monoclinic space group P2 1/c, with cell parameters a = 10.902 5(4) A, b = 6.226 1(3) A, c = 14.031 8(5) A, and z = 4. The lattice parameters of the substances were also determined by using powder diffraction methods. The functional groups are identified by using FTIR spectral analysis. The absorbance of title compound were analyzed using UV-Vis spectra. The thermo analytical properties of the crystal were studied using TG, DTA. PMID- 26904851 TI - Heavy Metals Contents and Speciation in Surface Sediments from Gansu, Ningxia and Inner Mongolia Sections of the Yellow River of China. AB - So far, many investigations had been made on the concentration and species distribution of heavy metals in aquatic environments. However, there are only a few studies on heavy metals in upper reaches of the Yellow River, especially in Gansu, Ningxia and Inner Mongolia sections. We have literatures related to the Yellow River, in this work, we remarkably discussed about the contents, speciation and potential risks of Cd, Pb, Cr, V, Co, Ni, Cu, and Zn in surface sediments from 12 sampling sites in Gansu, Ningxia, and Inner Mongolia sections of the Yellow River of China in 2011 year wet season by high resolution inductively coupled plasma mass spectrometer (HR-ICP-MS) and sequential extraction procedure of BCR method. The results indicated that the metals contents were arranged as Cr > V > Zn > Cu > Ni > Pb > Co > Cd in all sites. Comparing with the background value of soil in local section, Cd showed the highest level at S5 (1.30 MUg x g(-1)), which was almost 13 times higher than the background value (0.103 MUg x g(-1)). Pollution assessment indicated that Cd presented a strong polluted status with the geo-accumulation index (I(geo)) value of 3.08 at S5, moderately to strong polluted status with the I(geo) ranged from 2.02 to 2.90 in Inner Mongolia section (S1-S4). Moreover, enrichment factor (EF) showed that all heavy metals in these sediments have been influenced by anthropogenic activities. According to potential ecological risk index (RI), S5 and S3 demonstrated high ecologic risk of heavy metals, while other sampling sites showed moderately ecological risk. The results of BCR exhibited that Cd was the most available metal, followed by Co and Ni, while V and Cr were unavailable in the sediments. Risk assessment code (RAC) exhibited high risk for Cd at S1-S4 and very high risk at S5, while medium risk for Ni and Co at all sites. The results and conclusions may be important information and therefore of interest to the relevant departments of the governments. PMID- 26904852 TI - A Study on Effect of Water Background on Canopy Spectral of Wetland Aquatic Plant. AB - Aquatic vegetation is the core of the wetland ecosystem, and it's also the main factor influencing the wetland ecosystem functions. In recent years, satellite remote sensing technology has been widely used in the investigation, classification and protection fields of wetland vegetation resources. Because of its unique growth environment, aquatic vegetation, the canopy spectrum of aquatic vegetation will be affected by water background elements including air-water interface, plankton in the water, sediment content, transparency, water depth, sediment, and the other optically active ingredients. When the remote sensing technology for wetland aquatic vegetation canopy spectral studies, should be considered the growth environment differences between aquatic and terrestrial vegetation. However, previous studies did not get the attention it deserves. This paper choose a typical water plant (Iris tentorium Maxim) as the research object, simulate the growth environment of wetland aquatic plants, use the feature spectrometer measurements the spectral reflectance of Iris tentorium Maxim vegetation canopy under different water depth gradient background (400-2 400 nm). Experimental results show that there is a significant negative correlation between background water depth and Iris canopy reflectance. Visible light band absolute correlation coefficient is above 0.9, near infrared band absolute correlation coefficient is above 0.8. In visible light and near infrared band, with water depth increases, the Iris canopy reflectance decreases obviously. Finally based on the highest correlation band of visible light and near infrared region (505, 717, 1 075 and 2 383 nm) established the linear equation between background water depth and the canopy reflectance, obtained the related parameters. PMID- 26904853 TI - [The Role of Leptin in Cognitive Development During Aging]. AB - Brain aging is accompanied by alternations of brain structure, functions and the cognitive impairment. With respect to cognitive decline, the elderly population is far from homogeneous, as well as heterogeneous, which presents successful aging, normal aging, mild cognitive impairment and Alzheimer's disease. Studies demonstrated that higher serum leptin levels are associated with normal cognition in older adults without significant neurological conditions, while it is lower in most mild cognitive impairment patients. Leptin can improve cognitive disorders and referred to as a potential cognitive enhancer. Therefore, low level of leptin plays an significant role in cognitive impairment development in elderly people. PMID- 26904854 TI - [Leptin Signalings and Leptin Resistance]. AB - Leptin plays a critical role in the regulation of energy balance and metabolic homeostasis. Impairment of leptin function is closely involved in the pathogenesis of obesity, diabetes mellitus and some other metabolic diseases. Leptin initiates intracellular signal transductions in the leptin-receptor expressing neurons in the central nervous system to exert its physiological functions. The fact that high circulating levels of leptin partially or completely fail to promote weight loss in obesity has given rise to the notion of "leptin resistance". Recently, the impairment of leptin signalings in the hypothalamus has been regarded as a critical contributor to leptin resistance. In this review, the studies on leptin signaling and leptin resistance are summarized with an emphasis on the progress made during the last five years. PMID- 26904855 TI - [Vitamin D3 and Male Reproduction]. AB - The classical effects of vitamin D3 are modulating calcium and phosphorus metabolic balance and maintaining bone health in vivo. It has been shown that vitamin D3 could regulate animal reproduction. Vitamin D metabolic enzymes synthesize and degrade active vitamin D3 and its metabolic intermediates, and active vitamin D3 exerts its biological effects through binding to vitamin D receptor (VDR). VDR and vitamin D metabolic enzymes expressed in male reproductive system, it suggest that vitamin D3 plays a pivotal role in male reproductive biology. In this review, we mainly focus on the progress of vitamin D3 and male reproduction to provide a theoretical basis for pushing forward the molecular mechanisms research of vitamin D3 effects on male reproduction and clinical therapy for male infertility. PMID- 26904856 TI - [The Research Advances of the Pathomechanism of Phantom Limb Pain (PLP)]. AB - Phantom limb pain (PLP) is a hallucination that the patient feels the existence off the limb after its loss and experiences somewhat pain of the missing limb. Such a pain normally appears in the distal end of the missing limb. Currently, the pathomechanism of PLP is still unclear, and the clinical research of PLP mainly relies on the subjective report of the patients and the psychophysical measurements. In this paper, we discuss extensively the pathomechanism of PLP, and summarize comprehensively the advanced methods for studying the pathomechanism of PLP. In short, the paper could deepen our understanding of the pathomechanism of PLP, and could serve as an effective instruction basis for researchers and doctors to diagnose and treat the PLP. PMID- 26904857 TI - [Lipodystrophies: the molecular mechanisms and clinical characteristics]. PMID- 26904858 TI - [The relevance between autophagy and vascular remodeling]. PMID- 26904859 TI - [The research progress in platelet-derived growth factor -mediated vascular smooth muscle cell function]. PMID- 26904860 TI - [Study of the relationship between microRNA and cardiovascular diseases]. PMID- 26904862 TI - [Endogenous cardiovascular bioactive peptides and atrial fibrillation]. PMID- 26904861 TI - [The role of LncRNA in diabetes and its complications]. PMID- 26904863 TI - [The research progress of PPARgamma in the Neurodegenerative disease]. PMID- 26904864 TI - [The neuroprotective effect of erythropoietin on Hypoxic preconditioning]. PMID- 26904865 TI - [A new approach to study the neuromechanisms underlying depressive behaviors: the application of optogenetics]. PMID- 26904866 TI - [The effect and mechanism of Myostatin on skeletal muscle, brown adipose tissue and white adipose tissue]. PMID- 26904867 TI - [The roles of endogenous bioactive peptides in vascular calcification]. PMID- 26904868 TI - [Dynamic Pulse Signal Processing and Analyzing in Mobile System]. AB - In order to derive dynamic pulse rate variability (DPRV) signal from dynamic pulse signal in real time, a method for extracting DPRV signal was proposed and a portable mobile monitoring system was designed. The system consists of a front end for collecting and wireless sending pulse signal and a mobile terminal. The proposed method is employed to extract DPRV from dynamic pulse signal in mobile terminal, and the DPRV signal is analyzed both in the time domain and the frequency domain and also with non-linear method in real time. The results show that the proposed method can accurately derive DPRV signal in real time, the system can be used for processing and analyzing DPRV signal in real time. PMID- 26904869 TI - [Detection of R-wave in Fetal EGG Based on Wavelet Transform and Matched Filtering]. AB - By analyzing the characteristics of maternal abdominal ECG (Electrocardiogram), a method based on wavelet transform and matched filtering is proposed to detect the R-wave in fetal EGG (FECG). In this method, the high-frequency coefficients are calculated by using wavelet transform. First, the maternal QRS template is obtained by using the arithmetic mean scheme. Finally, the R-wave of FECG is detected based on matched filtering. The experimental results show that this method can effectively eliminate the noises, such as the maternal ECG signal and baseline drift, enhancing the accuracy of the detection of fetal ECG. PMID- 26904870 TI - [Anesthesia in the Signal Processing Methods]. AB - Anesthesia plays an essential role in clinical operations. Guiding anesthesia by EEG signals is one of the most promising methods at present and it has obtained good results. The analysis and process of the EEG signals in anesthesia can provide clean signal for further research. This paper used variance threshold method to remove the mutation fast and large interfering signals; and used notch filter to remove frequency interference, smoothing filter to remove baseline drift and Butterworth low-pass filter to remove high frequency noise at the same time. In addition to this, the translation invariant wavelet method to remove interference noise on the signals which was after the classical filter and retained non-stationary characteristics was used to evaluate parameter calculation. By comparing the calculated parameters from treated signal using this paper's methods and untreated signal and standard signal, the standard deviation and correlation has been improved, particularly the major parameters BetaR, which provides better signal for integration of multi-parameter to evaluate depth of anesthesia index for the latter. PMID- 26904871 TI - [The Development and Application of the Orthopaedics Implants Failure Database Software Based on WEB]. AB - This article develops a new failure database software for orthopaedics implants based on WEB. The software is based on B/S mode, ASP dynamic web technology is used as its main development language to achieve data interactivity, Microsoft Access is used to create a database, these mature technologies make the software extend function or upgrade easily. In this article, the design and development idea of the software, the software working process and functions as well as relative technical features are presented. With this software, we can store many different types of the fault events of orthopaedics implants, the failure data can be statistically analyzed, and in the macroscopic view, it can be used to evaluate the reliability of orthopaedics implants and operations, it also can ultimately guide the doctors to improve the clinical treatment level. PMID- 26904872 TI - [Design of Fall Detection System for Elderly People Based on MPU6050 Sensor]. AB - This paper proposes a falling detection system based on MPU6050 senor. The system consists of a MPU6050 sensor, a STM32 MCU and a set of Bluetooth 4.0 device: collecting and parsing the falling data, transferring the result to a smartphone, the smartphone: receiving the result, alarming the elder's family and hospital. This paper presentes a new judging algorithm based on the threshold of three-axis acceleration and angle deviation of body, in order to differentiate AF and normal daily activity. The result proves that the accuracy of the system is higher than 95%, which strongly highlight the robustness and reliability. PMID- 26904873 TI - [The Development of Anastomat of Digestive Tract Based on the Magnetic Compressive Technique]. AB - A new anastomat for digestive tract operations, based on the magnetic compressive technique and mechanical transmission mechanism, is composed of a removable head and a reusable body. The head includes two parts: the proximal end can be fixed to the body, and the distal end could be used for performing a purse string suture. The procedure of anastomosis is similar to that of the stapler, and the anastomoses is established using a pair of magnetic rings. The instrument makes magnamosis more simple and feasible, and it would facilitate the clinical application. The body of the anastomat is reusable and the head could be replaced according to the clinical scenarios, these could reduce the medical cost. The magnetic rings would be excreted with the feces, and there is no foreign body response at last. PMID- 26904874 TI - [Vein Scanning Projection Instrument Based on Two-Dimensional Scanning Mirror]. AB - With the development of science and technology, new medical equipments is toward the direction of intelligent and portable. In order to assist medical personnel to patients with blood, developing from previous devices, a new kind of vein locating projection instrument based on two-dimensional scanning mirror is put forward. It can scan and project vein image using a scanning mirror. The related algorithm is also be improved, make vein scan projection more practical. The system finally set up can perform well in vein scan projection. PMID- 26904875 TI - [Development of a High Power Green Laser Therapeutic Equipment for Hyperplasia of Prostate]. AB - The basic theory of high power green laser equipment for prostate hyperplasia therapy and the components of the system developed are introduced. Considering the requirements of the clinical therapy, the working process of the high power green laser apparatus are designed and the laser with stable output at 120 W is achieved. The controlling hardware and application software are developed, and the safety step is designed. The high power green laser apparatus manufactured with characteristics of stable output, multifunctional and friendly interface provides a choices of prostate hyperplasia therapy for using nationalization instrument. PMID- 26904876 TI - [Design of Non-Invasive Blood Oxygen Measurement Based on AFE4490]. AB - From the perspective of portable monitoring devices,we use an analog front-end AFE4490 design a module of Non-invasive blood oxygen measurement, used to collect human pulse wave signal and peak (valley) value detection and then use the principles of non-invasive oximetry calculated oxygen saturation (SPO2). This design of noninvasive oximetry module has the characteristics of small size, low power consumption, and the results of test show that the measurement of oxygen saturation are correct. PMID- 26904877 TI - [Study on Intelligent Automatic Tracking Radiation Protection Curtain]. AB - In order to overcome the shortcomings of traditional X-ray inspection taking passive protection mode, this paper combines the automatic control technology, puts forward a kind of active protection X-ray equipment. The device of automatic detection of patients receiving X-ray irradiation part, intelligent adjustment in patients and shooting device between automatic tracking radiation protection device height. The device has the advantages of automatic adjustment, anti radiation device, reduce the height of non-irradiated area X-ray radiation and improve the work efficiency. Testing by the professional organization, the device can decrease more than 90% of X-ray dose for patients with non-irradiated area. PMID- 26904878 TI - [Design of the Rolling Type Nasal Feeding Perfusion Apparatus]. AB - At present, the existing problem in nasal feeding perfusion apparatus is laborious and instability. Designing the rolling type perfusion apparatus by using a roller pump, the problem is solved. Compared with the traditional perfusion apparatus, the advantage lies in liquid carrying only need once and simulating human swallowing process. Through testing and verification, the apparatus can be used in nasal feeding perfusion for elderly or patients. PMID- 26904879 TI - [The Feasibility Study on the Application of Global Medical Device Nomenclature(GMDN)]. AB - The article has analyzed the policy co-ordination, Industry coverage and technical experience of the global medical device nomenclature (GMDN) to our country, argued the feasibility on the application of GMDN in our medical device administration system, provided some reference on building the naming system of medical device in our country. PMID- 26904880 TI - [On the Status of the Domestic Mobile Medical Software Supervision]. AB - With the widespread use of smart phones, mobile medical class of applications use more widely. The regulation for medical applications is in the offing in domestic. How to effectively regulate such software to control its risks for patients is needed to solve. In this paper, the status of such simple software monitoring in domestic and abroad is analyzed, some problems of domestic mobile medical applications are summarized and some recommendations are proposed for the relevant departments. PMID- 26904881 TI - [The Situation and Countermeasures of the Undocumented in Vitro Diagnostic Reagents Urgently Needed in Clinical]. AB - We found that the number of institutions made use of the undocumented in vitro diagnostic reagent in the survey. The phenomenon poses some risks and problems. In use this paper, we analyzed the situation and the reasons for the use of the undocumented in vitro diagnostic reagents, and put forward the corresponding measures. PMID- 26904882 TI - [Safety/Effectiveness Evaluation Consideration of Three-Dimensional Ultrasonography Products]. AB - This article introduces three-dimensional ultrasonography products comprehensively, considers the evaluation of their safety and effectiveness and gives some opinions on technical review. It is hoped to be helpful for three dimensional ultrasonography products registration and technical review. PMID- 26904883 TI - [Discussion on Current Registration Situation and Problems of in Vitro Diagnostic Device of Tumor Marker]. AB - This paper aims to analysis of the general problem in the registration dossier and make recommendations on in vitro diagnostic device of tumor markers. On the basis of introducing declarations of the reagents, analysis registration dossier common problems occurs in the products intend to detect novel tumor markers and the combined detection product for multiple tumor markers, and analysis the special requirements for such products. PMID- 26904884 TI - [Method to Calculate the Yield Load of Bone Plate in Four-point Bending Test]. AB - This paper developed a calculation method to acquire the yield load P of bone plate during four-point bending test. This method is based on the displacement- force (delta-F) curve function f(M)(delta) obtained from the test, each slope of the curve was calculated using piecewise smooth function and the line segment in f(M)(delta) elastic deformation area was searched by setting the minimum slope T. Slope S was obtained through linear fit so as to build parallel displacement function f(L)(delta). Then, approximating intersection point of f(M)(delta) and f(L)(delta) was obtained through linear interpolation. Thus, yield load P was acquired. The method in the paper was loyal to YY/T 0342-2002 regulation and was liable to program calculation. The calculating process was nothing to do with whether the initial point during the test was preloaded or unloaded, and there was no need to correct the original point. In addition, T was set in an ideal fitting level guaranteed by the fitting coefficient of determination R2, and thus S was very close to the real value, and P was with a high accuracy. PMID- 26904885 TI - [Strategy Discussion for Pollution Control of Post-Consumer Home Medical Equipment]. AB - Compared with the recycle of post-consumer medical equipments in medical institutions, the treatment of post-consumer home medical equipments (HME) should be consummated in the field of academic research, policy and regulatory plus corresponding supporting industries. The HME industry situation and its classification, main components and properties are reviewed in this paper. The merits and demerits of various pollution control techniques in the recycle of post-consumer medical equipments are analysed. For instance, the source control techniques to improve the property of raw materials, the end treatment technique to recycle the HME and regenerate energy are also discussed. Further, the development prospect of pollution control technique in the recycle of HME and the challenges must face up to are also probed. PMID- 26904886 TI - [Opinion on the Industry Standard for Laparoscopic Trocar]. AB - There are some limits and irrationality in practical application of the clause 3.1, 3.2, 4.4.2, 4.5.2, 4.9.1 of YY 0672.1-2008 as the industry standard for laparoscopic trocar. This paper puts forward some opinion and advice. PMID- 26904887 TI - [Understanding and Thinking on America Clinical Evaluation of Medical Devices]. AB - This paper introduces the risk classification and listing way of medical devices in the United States, and according to the contents in various situations, FDA provides the requirements for clinical evaluation. At the same time, through the comparative study on the similarities and differences between USA and our country of the clinical evaluation, the paper puts forward some suggestions. PMID- 26904888 TI - [PDCA Applied in Special Rectification of Medical Instrument Clinical Trial]. AB - PDCA cycle was applied in special rectification activities for medical instrument clinical trial, with quality criteria of implementation made. Completed medical instrument clinical trial from January 2011 to December 2012 was believed as control group, from January 2013 to December 2014 as PDCA group, the scores of clinical trial and the score rate of items were compared and analyzed. Results show quality scores of clinical trial in PDCA group are higher than that in control group (51 vs. 81, P < 0.001), score rate of items increased except adverse events (P < 0.001). The special rectification activities with PDCA applied in our department are feasible and effective. It significantly improves implement quality of medical instrument clinical trial. PMID- 26904889 TI - [Analysis of Factors on Clinical Application of Vehicle CT Shelter]. AB - To assure the clinical quality and requirement of CT shelter used in field environment, the factors related with the practical application were studied. The evaluation indicators of CT equipment were investigated. Based on the technical modification of vehicle shelter CT, the scanning conditions of shelter CT were analyzed. Moreover, the comparative study was done between shelter CT and common CT in hospitals. In result, in order to meet maneuverability application in the field, vehicle shelter CT was restrictive by the field conditions, traffic impacts and running requirement. The application of vehicle shelter CT was affected by the factors, such as mechanical stabilization, moving precision, power fluctuations and variations of temperature and humidity, etc. The results were helpful to improve the clinical quality of vehicle shelter CT and made a base for the quality control study in the future. PMID- 26904890 TI - [Medical Equipment Maintenance Methods]. AB - Due to the high technology and the complexity of medical equipment, as well as to the safety and effectiveness, it determines the high requirements of the medical equipment maintenance work. This paper introduces some basic methods of medical instrument maintenance, including fault tree analysis, node method and exclusive method which are the three important methods in the medical equipment maintenance, through using these three methods for the instruments that have circuit drawings, hardware breakdown maintenance can be done easily. And this paper introduces the processing methods of some special fault conditions, in order to reduce little detours in meeting the same problems. Learning is very important for stuff just engaged in this area. PMID- 26904891 TI - [Puncture Point Hemostatic Effect Observation of Different Materials with Modified Seldinger Technique in PICC Catheter]. AB - OBJECTIVE: To explore the improvement the dingle technology through the PICC catheter puncture point elbow hemostatic effect. Selection. METHODS: Between January 2013 and December 2013, chest hospital affiliated to Shanghai jiaotong university under the guidance of ultrasound improved the Ding Gehang PICC catheter patients of 997 cases were randomly divided into three groups A, B, C, respectively, using gauze pad, calcium alginate wound dressings, calcium alginate wound dressings with hemostatic gauze pad three methods to puncture point, compare the three groups within 48 h after puncture biopsy in patients with some local bleeding, treatment times and catheter after 1 week of the maintenance costs of the catheter. RESULTS: Compared with A, B two groups, patients of group C tube after 48 hours the puncture point local oppression hemostasis effect is better than that of group A and B, the difference was statistically significant (all P < 0.05); Catheter maintenance: group C within 1 week after catheter tube after local lowest maintenance cost. CONCLUSION: PICC for surgery after the puncture point of oppression hemostasis method choice, the effect of calcium alginate dressings hemostatic gauze pad is better than that of gauze pads and calcium alginate dressings, calcium alginate dressings and gauze pad is more effective and economic, in clinical use. PMID- 26904892 TI - [Literature review of the influences on error rates when identifying equids with transponder and hot-iron branding]. AB - Although equids have had to be tagged with a transponder since 2009, breeding associations in Germany disagree as to which method is best suited for identification (with or without hot iron branding). Therefore, the aim of this systematic literature review was to gain an overview of how effective identification is using transponders and hot iron branding and as to which factors influence the success of identification. Existing literature showed that equids can be identified by means of transponders with a probability of 85-100%, whereas symbol brandings could be identified correctly in 78-89%, whole number brandings in 0-87% and single figures in 37-92% of the readings, respectively. The successful reading of microchips can be further optimised by a correctly operated implantation process and thorough training of the applying persons. affect identification with a scanner. The removal of transponders for manipulation purposes is virtually impossible. Influences during the application of branding marks can hardly, if at all, be standardised, but influence the subsequent readability relevantly. Therefore, identification by means of hot branding cannot be considered sufficiently reliable. Impaired quality of identification can be reduced during reading but cannot be counteracted. Based on the existing studies it can be concluded that the transponder method is the best suited of the investigated methods for clearly identifying equids, being forgery proof and permanent. It is not to be expected that applying hot branding in addition to microchips would optimise the probability of identification relevantly. PMID- 26904893 TI - [Animal hygiene, water quality and animal health using round drinkers as an animal-friendly water supply for Pekin ducks under practical conditions]. AB - Mandatory requirements for the keeping of Pekin ducks exist neither in Europe nor in Germany. The medium water is of high importance for ducks and is connected with many species-specific behaviours. In commercial fattening establishments the animals are provided drinking water solely by nipple drinkers because up to today, the economic and hygienic aspects of this drinking suppIy are beyong dispute. The aim of the study was to examine the influence of the round drinker AquaDuc T(r) on animal hygiene and different health parameters in three commercial farms. The examinations took place in three fattening farms (7140 13,515 fattening places). Per farm 16 fattening periods were surveyed (alternately control and test trial) with one visit each between 28th-32nd and 35th-39th day of life. On one farm only ten periods could be examined. The ducks were provided with water by nipple drinkers. Additionally, the AquaDuc T(r) was installed in the test trials, which was temporarily accessible. Apart from health evaluations of each 100 animals, barn climate (dust and gaseous ammonia content) and quality of drinking water were examined. In summary it can be stated that concerning health evaluation (eye infection/ plugged nostrils) the ducks with access to round drinkers mostly performed better than the animals with access solely to nipple drinkers. In this study the total bacteria count as well as the number of Enterobacteriaceae in CFU/mI was generally higher in the round drinkers compared to the nipple drinkers (average total germ count in CFU/ml: nipple drinker 10,950; round drinker 3,955,846), no negative effect on the health of Pekin ducks could be detected in this study. Sufficient hygiene of the offered drinking systems is essential for the wellbeing of the ducks. PMID- 26904894 TI - [Use of the AquaDuc T(r) round drinker with Pekin ducks under field conditions- behaviour as one indicator of welfare]. AB - Pekin ducks have an innate affinity for water. They seek water from the first day of life and use it for a multitude of behaviors. Currently implemented requirements to husbandry and the design of an animal-friendly offer of drinking water in commercial fattening establishments exist neither at EU-level nor in Germany. Aim of the study was to examine the use of the AquaDuc T(r) (Big Dutchman, Vechta, Germany) and its practical suitability concerning the behavior during the fattening of Pekin ducks under commercial conditions. The examinations took place in three farms (7140-13,515 fattening places). On farm 1 and 3, 16 fattening periods were observed (switch-over design: alternately test and control trial) with each one visited between day 28-32 and 35-39. On farm 2, only ten fattening periods could be examined. The ducks were in general supplied with drinking water via nipple drinkers. For the test trials, the AquaDuc T(r) drinkers were additionally installed and were accessible for a limited time. To record the natural and undisturbed behavior of the ducks in their housing system, the video recordings were started after we finished the farm visits and in total more than 6300 hours of video material were analyzed. All findings show that Pekin ducks clearly favor the round bell drinkers over the nipple drinkers. They enable the birds to immerse their heads, to drink and strain in a species specific manner, to take care of the plumage with water and to clean beak and eyes. In the test trials, the drinking activity rose significantly during the operating time of the round drinkers (p < 0.001), whereas the nipple drinkers were used less frequently at the same time. Concerning ethology and health, the round drinkers offer the ducks very good conditions for an animal-friendly water supply. For economic and hygienic reasons, the daily access to the modified round drinkers should be limited. PMID- 26904895 TI - Evaluation of the anaesthetic depth during piglet castration under an automated isoflurane-anaesthesia at farm level. AB - Piglet castration under isoflurane-anaesthesia could represent an alternative to the practice of castration without anaesthesia. The objective of this study was to evaluate practicality and effectiveness of an automated isoflurane-anaesthesia for castration. A field study on three different farms in Germany (farm A, B: 200 sows; C: 540 sows) was performed. In total, 1429 (1166 anaesthetised and 263 conventionally castrated) male piglets (age: 1-8 days; bodyweight: 0.7-3.7 kg) were monitored. All piglets were treated with nonsteroidal anti-inflammatory drugs directly before castration. Castration and anaesthesia were performed by the farm-manager in presence of a veterinarian. All farmers used the PIGNAP Pro(r) (Agrosystems GmbH, CH) anaesthetic device (5 vol.% isoflurane, 30% oxygen; flow rate: 2 l/min). Vocalisation and defensive movements of 1166 anaesthetised piglets was rated using a scoring system. Presence or absence of the palpebral- and flexor-reflex was noted. Approximately every second piglet was weighed and oxygen-saturation and pulse- frequency of 231 animals were measured during treatment. Rectal temperatures before and after castration of 264 anaesthetised and 263 conventionally castrated piglets were compared. Only 77% of the anaesthetised piglets showed a sufficient anaesthetic depth based on the assessment of reflexes as well as vocalisations and defensive movements. It was found that the probability for a sufficient depth of anaesthesia decreases with increasing age and weight. The measurements of the pulse-frequency and oxygen saturation showed an average oxygen-saturation of 98% and an average heart rate of 270/min during anaesthesia. The conventionally castrated piglets had significantly higher rectal temperatures in comparison to the anaesthetised (p < 0.0001). The result of 77% sufficiently anaesthetised piglets is not adequate for commercial application of this technology. PMID- 26904896 TI - Prevalence and antimicrobial resistance of Vibrio spp. in retail shrimps in Vietnam. AB - The aim of the study was to investigate the prevalence and the antimicrobial resistance patterns of Vibrio (V.) spp. isolated from retail shrimp in Hanoi, Vietnam A total of 202 shrimp samples were collected from retail markets located in ten urban districts of Hanoi. Among those, 201 (99.5%) samples were positive for Vibrio spp. The most common species detected was V parahaemolyticus (96.5%), followed by V. alginolyticus (56.4%), V. cholerae (2%) and V. vulnificus (1.5%). Multiple Vibrio spp. were found in 114 (56.4%) samples. None of the V. parahaemolyticus isolates carried the virulence-associated tdh (thermostable direct haemolysin) and trh (tdh-related haemolysin) genes. In total, 195 V. parahaemolyticus isolates, four V. cholerae isolates and three V. vulnificus isolates were tested for resistance to eight antimicrobial agents. V. parahaemolyticus isolates showed high rates of resistance against ampicillin (87.2%), while a moderate rate was observed for sulfamethoxazole/trimethoprim (18.5%) and intermediate resistance towards tetracycline (24.6%). Low resistance rates (0.5%) were recorded against both ciprofloxacin and cefalothin. Only one V. cholerae isolate with resistance to ampicillin and two V. cholerae isolates with resistance to sulfamethoxazole/trimethoprim were found. All V. vulnificus isolates were susceptible to the eight antimicrobial agents tested. However, the number of V. vulnificus and V. cholerae was small. Multi-resistant isolates were found in V. parahaemolyticus with a low frequency (16.9%). The results of this study revealed the ubiquitous nature of Vibrio spp. in shrimp at retail. To reduce the potential risk of Vibrio infections due to handling or consumption of undercooked seafood, good manufacturing practice as well as safe handling and processing should be encouraged. PMID- 26904897 TI - Eimeria leuckarti infections in sport horses in Northwest Turkey. AB - The aim of the present study was to examine sport horses in Northwest Turkey for Eimeria (E.) leuckarti infections. Between 2004 and 2008 fecal samples from 549 horses of different age, breed and sex of 21 farms were examined for E. leuckarti oocysts using a qualitative method which involved centrifugation/flotation and saturated sugar solution as medium. The prevalence of infection was evaluated relative to host age, sex, breed and pasture availability. 16 (2.9%) horses were found to be infected with E. leuckarti, whilst infected horses were located in nine (42.8%) farms. Younger horses (< 1 year old) were more frequently infected than older ones. However, breed, sex and availability of pasture were not identified as factors influencing the prevalence. As a main conclusion, compared with the low infection rate found in individual horses, E. leuckarti was highly prevalent at the farm level which possess a permanent risk of infection of especially younger horses at these premises. This study reports for the first time on the prevalence of E. leuckarti in sport horses from farms in Northwest Turkey. PMID- 26904898 TI - Parasites of sheep herding dogs in central Germany. AB - This paper reports on endoparasite infections diagnosed in 2012 by standard coproscopical techniques and coproantigen Giardia ELISA in 165 dogs used for sheep herding in 36 farms in central Germany. The overall prevalence of dogs with evidence of endoparasite infections was 27.3% (95% CI 20.6-34.7). The most frequently identified faecal forms were those of ascarids (Toxocara, 6.7%; Toxascaris 3.6%), hookworms (5.5%) and taeniid cestodes (4.2%), followed by those of Trichuris whipworms (3.0%), Capillaria aerophila (1.8%), Angiostrongylus and Crenosoma lungworms (1.2% each) and Cystoisospora canis coccidians (0.6%). Molecular identification demonstrated the seven dogs shedding taeniid eggs positive for Taenia (T.) species tapeworms (five, T. hydatigena; one, T. ovis; one Taenia sp.). Screening of the faeces with the coproantigen ELISA revealed Giardia specific antigen in 5.5% of the samples. The majority of the dogs had evidence of single endoparasite infections (22.4%) while evidence for infection with two or three parasites concurrently was found in six (3.6%) and two (1.2%) of the dogs, respectively. Dogs <= 1 year (n = 19) were parasitized more frequently (p < 0.05) with overall gastrointestinal parasites (63.2% vs. 20.5%), ascarids (36.8% vs. 6.8%) and Giardia spp. (21.1% vs. 3.4%) than older dogs (n = 146). Dogs which had been wormed within six months of examination tested less frequently positive for gastrointestinal helminths compared to dogs not wormed (11.1% vs. 25.0%; p = 0.0567). In addition, ear swabs taken from 43 sheep dogs in 2012 were examined, and Otodectes cynotis mites were extracted from one dog. Identification of ectoparasites collected by full body search and combing from 113 sheep dogs in the years 2011 to 2013 revealed infestation of fleas and ticks (each up to five specimens per dog) on 13 and 108 dogs, respectively, with nine dogs carrying both fleas and ticks. Archaeopsylla erinacei, Ctenocephalides (C) canis, C. felis and Pulex irritans fleas were identified from one, three, two and eleven dogs, respectively. Dermacentor reticulatus, Ixodes (I.) hexagonus and I. ricinus ticks were isolated from 16, eight and 95 dogs, respectively. PMID- 26904899 TI - Avian mycobacteriosis caused by Mycobacterium avium subspecies avium in four ornamental birds and in vitro drug sensitivity testing of isolates. AB - Avian tuberculosis, one of the most important diseases affecting various species of birds, is most often caused by Mycobacterium (M.) avium. This report describes cases of M. avium subsp. avium (MAA) infection in a white-crested Holland dwarf rooster, a male and a female golden pheasant and a male peacock. We also investigated the prevalence of mycobacteria in 60 other birds and 40 alpacas. Tissue samples of necropsied birds were cultured for mycobacteria. From non necropsied 60 other birds and alpacas only faecal samples were collected. Clinical signs in the affected white-crested Holland cock included gradual loss of body weight and hoarse attempts at crowing during its last 3 weeks, with a dramatic loss of body condition and depression over the final week. Only slight weakening was observed in the peacock just before its death, and the golden pheasants died suddenly. Diagnosis was confirmed by microbiological, molecular and pathological results. Mycobacterium avium subsp. avium strains were isolated from the internal organs of the affected birds. Only one faecal sample from 60 other birds was culture- and PCR-positive for M. avium subsp. avium, while another one was only PCR-positive for M. chelonae. We did not isolate any Mycobacterium spp. from faecal samples of alpacas and all of them were PCR negative. All 18 isolated M. avium strains were resistant to rifampicin, isoniazid, ethambutol, ethionamide, capreomycin and ofloxacin, and susceptible to cycloserine and streptomycin. PMID- 26904900 TI - Understanding barriers to following advice: Evaluation of an advisory service from dairy farmers' perspectives. AB - In dairy herd health medicine, the success of consultation is sometimes limited as farmers do not always implement given advice. Therefore, the objective of this study was to evaluate a consultation performed during a study in the northwest of Germany and thereby to detect barriers that hinder farmers with long lasting problems in herd health from implementing veterinary advice. Six to twelve months after a non-recurring extensive herd health analysis and consultation, 38 farmers were interviewed by phone. Nearly all farmers were content with the farm visit, and 79% of the farmers stated that they had implemented at least some of the advice. This shows that farmers appreciated this service in general and were willing to follow advice. Even though the results cannot be generalized, factors that could be considered by advisors to improve the success of consultation were detected: Reasons as to why the advice was rejected were mostly related to farmers' expectations. Implementing only some of the advice was caused by a lack of time, self-discipline, money, and a lacking farm successor. Factors that pleased farmers were friendliness of the study veterinarians, in-depth examinations, handling of cows, good advice and how well organized the farm visit was. Factors that displeased the farmers were usually indicated only by one farmer each. Other factors influencing the success of consultation were the teamwork with the practising veterinarian, the self-evaluation of the farmers and the desire of the farmers for a single reason for the herd health problems. PMID- 26904901 TI - [An unusual case of a 35 days preterm birth of a German Holstein calf]. AB - A female calf of the breed German Holstein (GH) was spontaneously born on July 28, 2013 which was 35 days before the expected term of birth. The dam was a heifer when she got pregnant from the first insemination on November 23, 2012. Calving was without complications. The calf was fully viable and without visible anomalies. We assume that the calf was fully mature at the termination of the pregnancy. Growth rate after the second month of life was comparable to calves born in the same herd after normal length of gestation. The sire of this preterm calf was a GH-bull used for artificial insemination. This bull had already sired 151 daughters. For this bull, preterm calvings were not yet reported. The dam was a heifer, and neither external influences on this dam or in the herd could be identified that could have induced this premature calving. In the herd, no further premature calvings were observed or reasons associated with a preterm calving were found. In this exceptional case, however, gestation length was 248 days and the prematurely born calf survived without any signs of debility, organ defects and respiratory distress. PMID- 26904902 TI - Tackling Disparities More Important Than Ever. AB - Hospitals are redoubling their efforts to identify and eliminate disparities in care. The #123forEquity Pledge to Act Campaign is one way you can get involved. PMID- 26904903 TI - Tales from the Revolution. PMID- 26904904 TI - Adaptability in the Face of Uncertainty. PMID- 26904905 TI - CROWNING ACHIEVEMENT. Hospitals increasingly add birth centers to labor and delivery offerings. PMID- 26904906 TI - SOCIALLY CONSCIOUS. Study: the power of social media to improve patient experience and quality. PMID- 26904907 TI - VALUE-BASED PAYMENT. Three questions with: John Brumsted, M.D. PMID- 26904908 TI - MOST WIRED. Creating health care value with big data intelligence. PMID- 26904909 TI - FASTER RESPONSE. Hospitals backing increased use of opioid antidote. AB - Hospitals are intensifying efforts to cut opioid abuse. One way is by donating a lifesaving drug to police departments. PMID- 26904910 TI - RAISING AWARENESS. Woman-to-woman heart care. PMID- 26904911 TI - Environmental services gospel choir raises a joyful noise. PMID- 26904912 TI - Today's Rural Trustees: ready for anything (and everything!). PMID- 26904913 TI - Designing Safer Hospitals: Evidence is Everything. PMID- 26904914 TI - New twists on services, with the OLDER PATIENT in mind. PMID- 26904915 TI - Stepping up against SEPSIS. AB - These hospitals have shown that a coordinated, low-cost strategy dramatically reduces infection and mortality. It's an approach others may want to adopt. PMID- 26904916 TI - Tumor Acidity-Induced Sheddable Polyethylenimine-Poly(trimethylene carbonate)/DNA/Polyethylene Glycol-2,3-Dimethylmaleicanhydride Ternary Complex for Efficient and Safe Gene Delivery. AB - Amphiphilic PEI derivatives/DNA complexes are widely used for DNA delivery, but they are unstable in vivo and have cytotoxicity due to the excess cationic charge. PEGylation of cationic complexes can improve sterical stability and biocompatibility. However, PEGylation significantly inhibits cellular uptake and endosomal escape. In this work, sheddable ternary complexes were developed by coating a tumor acidity-sensitive beta-carboxylic amide functionalized PEG layer on the binary complexes of amphiphilic cationic polyethylenimine poly(trimethylene carbonate) nanoparticles/DNA (PEI-PTMC/DNA). Such sheddable ternary complexes markedly reduced their nonspecific interactions with serum protein in the bloodstream and obtained minimal cytotoxicity due to the protection of the PEG shell. At the tumor site, the PEG layer was deshielded by responding to the tumor acidic microenvironment and the positively charged complexes re-exposed that had higher affinity with negatively charged cell membranes. Meanwhile the positively charged complexes facilitated endosomal escape. Accordingly, this delivery system improved the biocompatibility of gene loaded complexes and enhanced the gene transfection efficiency. Such PEGylated complexes with the ability to deshield the PEG layer at the target tissues hold great promise for efficient and safe gene delivery in vivo. PMID- 26904917 TI - Hepatitis C virus and HIV seroprevalences, sociodemographic characteristics, behaviors and access to syringes among drug users, a comparison of geographical areas in France, ANRS-Coquelicot 2011 survey. AB - BACKGROUND: People who use drugs (PWUDs) are at a high risk for hepatitis C virus (HCV) and human immunodeficiency virus (HIV), but they have different characteristics depending on the local context. In France, seroprevalence, sociodemographic, and behavior information have only been studied at a national level rather than at a local level. The aim of this study was to describe and examine profile and drug use practice differences in seven French cities and departments and to assess whether these differences can explain HCV and HIV seroprevalence variations between French geographical areas. METHODS: Data were collected from the cross-sectional ANRS-Coquelicot survey conducted for the second time in 2011 among drug users having injected or snorted drugs at least once in their life. Professional interviewers administrated a face-to-face questionnaire in six different areas in France: Paris, Marseille, Bordeaux, Lille, Strasbourg and the Seine-Saint-Denis department (Paris suburbs). Participants were asked to self-collect a fingerpick blood sample in order to search for the presence of anti-HIV and anti-HCV antibodies and to estimate seroprevalence in PWUDs. RESULTS: Overall, HCV and HIV seroprevalence was 44% [95% CI: 39.6-47.9] and 10% [95% CI: 7.5-12.6] respectively. The highest HCV seroprevalence was 56% in Marseille and the lowest was 24% in Bordeaux and for HIV the highest was 18% in Seine-Saint-Denis and the lowest was 0% in Lille. The population's age differed between areas and could mostly explain HCV seroprevalence variation but not exclusively. Profiles and practices, different in each area, can also explain this variation. In multivariate analysis, HCV seroprevalence was lower in Bordeaux (prevalence ratio [PR]=0.64), Strasbourg (PR=0.76), and Seine-Saint-Denis (PR=0.8) than in Paris. Nearly one-third of injectors declared having had difficulties to obtain syringes in the 6 previous months, but disparities existed between areas. CONCLUSION: HCV risk exposure in PWUDs remains high in France and varies between different areas. Innovative harm reduction strategies including educative programs about safe injecting and supervised consumption rooms need to be developed. PMID- 26904918 TI - Design, fabrication and characterization of a pure uniaxial microloading system for biologic testing. AB - The field of mechanobiology aims to understand the role the mechanical environment plays in directing cell and tissue development, function and disease. The empirical aspect of the field requires the development of accurate, reproducible and reliable loading platforms that can apply microprecision mechanical load. In this study we designed, fabricated and characterized a pure uniaxial loading platform capable of testing small synthetic and organic specimens along a horizontal axis. The major motivation for platform development was in stimulating bone cells seeded on elastomeric substrates and soft tissue loading. The biological uses required the development of culturing fixtures and environmental chamber. The device utilizes commercial microactuators, load cells and a rail/carriage block system. Following fabrication, acceptable performance was verified by suture tensile testing. PMID- 26904919 TI - Stress shielding in bone of a bone-cement interface. AB - Cementation is one of the main fixation methods used in joint replacement surgeries such as Total Knee Replacement (TKR). This work was prompted by a recent retrieval study, which shows losses up to 75% of the bone stock at the bone-cement interface ten years post TKR. It aims to examine the effects of cementation on the stress shielding of the interfacing bone, when the influence of an implant is removed. A micromechanics finite element study of a generic bone cement interface is presented here, where bone elements in the partially and the fully interdigitated regions were evaluated under selected load cases. The results revealed significant stress shielding effect in the bone of all bone cement interface regions, particularly in fully interdigitated region. This finding may be useful in the studies of implant fixation and other related orthopedic treatment strategies. PMID- 26904920 TI - Vitamin D Receptor Polymorphisms Relate to Risk of Adenomatous Polyps in a Sex Specific Manner. AB - Vitamin D receptor (VDR) gene polymorphisms may influence risk for adenomatous polyps (AP), a benign precursor to colon cancer, via modulation of vitamin D sensitive pathways, including cell proliferation and differentiation. However, results have been mixed and any association remains contentious. Failure to clinically exclude the presence of (AP in control cohorts may contribute to the lack of consensus. Therefore, we assessed the role of the FokI, BsmI, ApaI, and TaqI VDR polymorphisms in modifying risk for AP, adjusting for a range of dietary and lifestyle variables. Blood was collected from colonoscopy patients (n = 258) and VDR polymorphisms assessed by restriction fragment length polymorphism. Dietary habits were estimated from food frequency questionnaires. Odds ratios for AP were calculated by genotype, stratified by sex, and adjusted for age, lifestyle, and dietary factors. FokI was associated with modified risk for AP in males, whereas the BsmI/ApaI/TaqI haplotype was associated with modified risk in females. No interaction was found between VDR variants and vitamin D intake. This study offers novel insight into the potential for VDR genetics to contribute to risk for AP and is the first to demonstrate a sex-specific relationship between these polymorphisms and risk for AP. PMID- 26904921 TI - Unique Polybrominated Hydrocarbons from the Australian Endemic Red Alga Ptilonia australasica. AB - The red alga Ptilonia australasica is endemic to Australian temperate waters. Chemical investigation of P. australasica led to the identification of four new polybrominated compounds, ptilones A-C (1-3) and australasol A (4). Their planar structures were established by extensive NMR and MS analyses. The low H/C ratio and the presence of a large number of heteroatoms made the structure elucidation challenging. The absolute configurations of 1, 2, and 4 were determined by quantum chemical ECD calculations employing time-dependent density functional theory. Ptilones A-C (1-3) show unique 4-ethyl-5-methylenecyclopent-2-enone (1 and 2) and 2-methyl-6-vinyl-4H-pyran-4-one (3) skeletons not previously reported in algal metabolites. Ptilone A displayed the most potent cytotoxicity against the human prostate cancer PC3 cells with an IC50 value of 0.44 MUM and induced the PC3 cell cycle arrest in the G0/G1 phase. PMID- 26904922 TI - A DNA Aptamer Against Influenza A Virus: An Effective Inhibitor to the Hemagglutinin-Glycan Interactions. AB - Most therapeutical nucleic acid aptamers tend to inhibit protein-protein interactions and thereby function as antagonists. Attachment of the influenza virus surface glycoprotein hemagglutinin (HA) to sialic acid-containing host cell receptors (glycan) facilitates the initial stage of viral infection. Inhibition of the attachment may result in an antiviral effect on the proliferation of the influenza virus. To develop therapeutically interesting agents, we selected two single-stranded DNA (ssDNA) aptamers specific to the HA protein of H1N1 influenza virus (A/Puerto Rico/8/1934) through a procedure of systematic evolution of ligands by exponential enrichment. As it showed a higher binding affinity for HA protein (Kd = 78 +/- 1 nM), aptamer 1 was tested for its ability to interfere with HA-glycan interactions using chicken red blood cell hemagglutination and microneutralization assays, which demonstrated that it significantly suppressed the viral infection in host cells. These results indicate that the isolated ssDNA aptamer may be developed as an antiviral agent against influenza through appropriate therapeutic formulation. PMID- 26904923 TI - Nutrient fluxes from domestic wastewater: A national-scale historical perspective for the UK 1800-2010. AB - Nutrient emissions in human waste and wastewater effluent fluxes from domestic sources are quantified for the UK over the period 1800-2010 based on population data from UK Census returns. The most important drivers of change have been the introduction of the water closet (flush toilet) along with population growth, urbanization, connection to sewer, improvements in wastewater treatment and use of phosphorus in detergents. In 1800, the population of the UK was about 12 million and estimated emissions in human waste were 37kt N, 6.2kt P and 205ktorganicC/year. This would have been recycled to land with little or no sewage going directly to rivers or coastal waters. By 1900, population had increased to 35.6 million and some 145kt N were emitted in human waste but, with only the major urban areas connected to sewers, only about 19kt N were discharged in sewage effluent. With the use of phosphorus in detergents, estimated phosphorus emissions peaked at around 63.5ktP/year in the 1980s, with about 28ktP/year being discharged in sewage effluent. By 2010, population had increased to 63 million with estimated emissions of 263kt N, 43.6kt P and 1460ktorganicC/year, and an estimated effluent flux of 104kt N, 14.8kt P and 63kt organic C. Despite improvements in wastewater treatment, current levels of nutrient fluxes in sewage effluent are substantially higher than those in the early 20th century. PMID- 26904924 TI - Redundancy in the ecological assessment of lakes: Are phytoplankton, macrophytes and phytobenthos all necessary? AB - Although the Water Framework Directive specifies that macrophytes and phytobenthos should be used for the ecological assessment of lakes and rivers, practice varies widely throughout the EU. Most countries have separate methods for macrophytes and phytobenthos in rivers; however, the situation is very different for lakes. Here, 16 countries do not have dedicated phytobenthos methods, some include filamentous algae within macrophyte survey methods whilst others use diatoms as proxies for phytobenthos. The most widely-cited justification for not having a dedicated phytobenthos method is redundancy, i.e. that macrophyte and phytoplankton assessments alone are sufficient to detect nutrient impacts. Evidence from those European Union Member States that have dedicated phytobenthos methods supports this for high level overviews of lake condition and classification; however, there are a number of situations where phytobenthos may contribute valuable information for the management of lakes. PMID- 26904927 TI - [New Developments in Video Games for Psychotherapy]. AB - A literature survey on new developments in the area of video games and psychotherapy of children and adolescents was conducted. Despite the omnipresence of computers and the internet, development of therapeutic games seems rather slow. The video game Treasure Hunt was introduced in 2008 to support treatment of children with internalizing and externalizing disorders. Camp Cope-A-Lot was developed for treatment of anxious children, whereas the self-help game SPARX is directed at depressed adolescents. Rage-Control is a biofeedback game for children with anger problems. The game Zoo U aims to assess and train social skills of primary school children. Ricky and the Spider for young children with obsessive compulsive disorder is meant to support the cognitive-behavioural treatment of these patients. Clash- Back is a French game for adolescents with externalizing problems. Possible reasons for the relatively slow development of therapeutic games are the high methodological demands concerning an evaluation as well as the high costs of game development. Nonetheless, computers and the internet are bound to influence psychotherapy with children and adolescents in the long run. PMID- 26904925 TI - An algorithm for expanding the TNM staging system. AB - AIM: We describe a new method to expand the tumor, lymph node, metastasis (TNM) staging system using a clustering algorithm. Cases of breast cancer were used for demonstration. MATERIALS & METHODS: An unsupervised ensemble-learning algorithm was used to create dendrograms. Cutting the dendrograms produced prognostic systems. RESULTS: Prognostic systems contained groups of patients with similar outcomes. The prognostic systems based on tumor size and lymph node status recapitulated the general structure of the TNM for breast cancer. The prognostic systems based on tumor size, lymph node status, histologic grade and estrogen receptor status revealed a more detailed stratification of patients when grade and estrogen receptor status were added. CONCLUSION: Prognostic systems from cutting the dendrogram have the potential to improve and expand the TNM. PMID- 26904928 TI - [Validated Instruments for the Psychological Assessment of Unaccompanied Refugee Minors - a Systematic Review]. AB - The German care system faces a growing number of unaccompanied refugee minors (URM). URM show high levels of traumatization, a variety of psychological symptoms and lack important resilience factors. Therefore an early and valid psychological assessment is important for intervention and service planning. Yet, no systematic review on validated instruments for the assessment of this group exists. Literature search revealed one study about translators in the assessment of URM and five validated instruments for proxy and self-report. These instruments are available in several languages and showed good psychometric properties. It has to be critically stated that all instruments have been validated by a single work group within a single population. Especially with regards to changing definitions of Posttraumatic Stress Disorder within the new (and upcoming) classification systems ICD-11 and DSM-5, increased awareness for diagnostic procedures is necessary. Additionally, more validated instruments for specific psychological disorders in multiple languages are needed. Under an economic perspective the use of open access questionnaires that are available in different languages seems useful, even if they are not especially validated for URM. PMID- 26904929 TI - [Referring Children who have Difficulties at School to Schools for Children with Special Needs: School Psychologists are Less Discriminating than Teaching Staff]. AB - Children from a migrant background fall through the regular education net more frequently than native children and are subjected disproportionately to special teaching methods that are both separative as well as integrative. Studies up to now show that the discriminating attributions made by teaching staff influence the referral practice significantly. Whether this is also true for school psychologists was unknown and was investigated in the study presented here. By way of the "practice testing" method, 207 school psychologists dealt with a hypothetical case involving a problem student whose first name and family ethnos were systematically varied. The results show that school psychologists are led by separating dispositions of action to a lesser extent than teaching staff and that for the most part they think "culturally neutrally". PMID- 26904930 TI - [ Symptom Severity and the Role of Friendship in Children at a Child Guidance Center from Parents' Point of View]. AB - By means of the Child Behavior Checklist (CBCL) it was assessed how much children who are attended to a child guidance center suffer from behavior problems and emotional distress. Furthermore, the interaction between straining and supporting influences was examined. Results show that symptom severity lies in the range of clinical significance. Children of divorced parents show more internalizing as well as externalizing problems than children of nuclear families. High social integration is correlated with lower psychic symptomatic - yet, this finding was dependent on family situation: While frequency to meet friends in children from nuclear families was correlated with lower symptomatic, this effect could not be found in children of divorced parents. PMID- 26904935 TI - Tunable Cascade Reaction of Aryl Diazonium Salts and Trialkylamine: Synthesis of Monofluorinated Arylhydrazones and gem-Difluorinated Azo Compounds. AB - The first example of a mild and tunable cascade reaction of aryl diazonium salts and trialkylamine in the presence of Selectfluor to prepare monofluorinated arylhydrazones and gem-difluorinated azo compounds without metal has been explored. In the presence of H2O, the monofluorinated arylhydrazones were observed in moderate to good yield. In the absence of H2O, the gem-difluorinated azo compounds were obtained. The fluorinated arylhydrazones were utilized to synthesize fluorinated pyrazoles and other nitrogen-containing compounds. PMID- 26904936 TI - NRF2 Orchestrates the Metabolic Shift during Induced Pluripotent Stem Cell Reprogramming. AB - The potential of induced pluripotent stem cells (iPSCs) in disease modeling and regenerative medicine is vast, but current methodologies remain inefficient. Understanding the cellular mechanisms underlying iPSC reprogramming, such as the metabolic shift from oxidative to glycolytic energy production, is key to improving its efficiency. We have developed a lentiviral reporter system to assay longitudinal changes in cell signaling and transcription factor activity in living cells throughout iPSC reprogramming of human dermal fibroblasts. We reveal early NF-kappaB, AP-1, and NRF2 transcription factor activation prior to a temporal peak in hypoxia inducible factor alpha (HIFalpha) activity. Mechanistically, we show that an early burst in oxidative phosphorylation and elevated reactive oxygen species generation mediates increased NRF2 activity, which in turn initiates the HIFalpha-mediated glycolytic shift and may modulate glucose redistribution to the pentose phosphate pathway. Critically, inhibition of NRF2 by KEAP1 overexpression compromises metabolic reprogramming and results in reduced efficiency of iPSC colony formation. PMID- 26904937 TI - Therapeutic Response to Non-genotoxic Activation of p53 by Nutlin3a Is Driven by PUMA-Mediated Apoptosis in Lymphoma Cells. AB - Nutlin3a is a small-molecule antagonist of MDM2 that promotes non-genotoxic activation of p53 through p53 protein stabilization and transactivation of p53 target genes. Nutlin3a is the forerunner of a class of cancer therapeutics that have reached clinical trials. Using transgenic and gene-targeted mouse models lacking the critical p53 target genes, p21, Puma, and Noxa, we found that only loss of PUMA conferred profound protection against Nutlin3a-induced killing in both non-transformed lymphoid cells and EMU-Myc lymphomas in vitro and in vivo. CRISPR/Cas9-mediated targeting of the PUMA gene rendered human hematopoietic cancer cell lines markedly resistant to Nutlin3a-induced cell death. These results demonstrate that PUMA-mediated apoptosis, but not p21-mediated cell-cycle arrest or senescence, is a critical determinant of the therapeutic response to non-genotoxic p53 activation by Nutlin3a. Importantly, in human cancer, PUMA expression may predict patient responses to treatment with MDM2 antagonists. PMID- 26904938 TI - Analogous Convergence of Sustained and Transient Inputs in Parallel On and Off Pathways for Retinal Motion Computation. AB - Visual motion information is computed by parallel On and Off pathways in the retina, which lead to On and Off types of starburst amacrine cells (SACs). The approximate mirror symmetry between this pair of cell types suggests that On and Off pathways might compute motion using analogous mechanisms. To test this idea, we reconstructed On SACs and On bipolar cells (BCs) from serial electron microscopic images of a mouse retina. We defined a new On BC type in the course of classifying On BCs. Through quantitative contact analysis, we found evidence that sustained and transient On BC types are wired to On SAC dendrites at different distances from the SAC soma, mirroring our previous wiring diagram for the Off BC-SAC circuit. Our finding is consistent with the hypothesis that On and Off pathways contain parallel correlation-type motion detectors. PMID- 26904939 TI - Insertional Mutagenesis Identifies a STAT3/Arid1b/beta-catenin Pathway Driving Neurofibroma Initiation. AB - To identify genes and signaling pathways that initiate Neurofibromatosis type 1 (NF1) neurofibromas, we used unbiased insertional mutagenesis screening, mouse models, and molecular analyses. We mapped an Nf1-Stat3-Arid1b/beta-catenin pathway that becomes active in the context of Nf1 loss. Genetic deletion of Stat3 in Schwann cell progenitors (SCPs) and Schwann cells (SCs) prevents neurofibroma formation, decreasing SCP self-renewal and beta-catenin activity. beta-catenin expression rescues effects of Stat3 loss in SCPs. Importantly, P-STAT3 and beta catenin expression correlate in human neurofibromas. Mechanistically, P-Stat3 represses Gsk3beta and the SWI/SNF gene Arid1b to increase beta-catenin. Knockdown of Arid1b or Gsk3beta in Stat3(fl/fl);Nf1(fl/fl);DhhCre SCPs rescues neurofibroma formation after in vivo transplantation. Stat3 represses Arid1b through histone modification in a Brg1-dependent manner, indicating that epigenetic modification plays a role in early tumorigenesis. Our data map a neural tumorigenesis pathway and support testing JAK/STAT and Wnt/beta-catenin pathway inhibitors in neurofibroma therapeutic trials. PMID- 26904940 TI - The Spindle Assembly Checkpoint Is Not Essential for Viability of Human Cells with Genetically Lowered APC/C Activity. AB - The anaphase-promoting complex/cyclosome (APC/C) and the spindle assembly checkpoint (SAC), which inhibits the APC/C, are essential determinants of mitotic timing and faithful division of genetic material. Activation of the APC/C is known to depend on two APC/C-interacting E2 ubiquitin-conjugating enzymes-UBE2C and UBE2S. We show that APC/C activity in human cells is tuned by the combinatorial use of three E2s, namely UBE2C, UBE2S, and UBE2D. Genetic deletion of UBE2C and UBE2S, individually or in combination, leads to discriminative reduction in APC/C function and sensitizes cells to UBE2D depletion. Reduction of APC/C activity results in loss of switch-like metaphase-to-anaphase transition and, strikingly, renders cells insensitive to chemical inhibition of MPS1 and genetic ablation of MAD2, both of which are essential for the SAC. These results provide insights into the regulation of APC/C activity and demonstrate that the essentiality of the SAC is imposed by the strength of the APC/C. PMID- 26904941 TI - Sharp-Wave Ripples Orchestrate the Induction of Synaptic Plasticity during Reactivation of Place Cell Firing Patterns in the Hippocampus. AB - Place cell firing patterns reactivated during hippocampal sharp-wave ripples (SWRs) in rest or sleep are thought to induce synaptic plasticity and thereby promote the consolidation of recently encoded information. However, the capacity of reactivated spike trains to induce plasticity has not been directly tested. Here, we show that reactivated place cell firing patterns simultaneously recorded from CA3 and CA1 of rat dorsal hippocampus are able to induce long-term potentiation (LTP) at synapses between CA3 and CA1 cells but only if accompanied by SWR-associated synaptic activity and resulting dendritic depolarization. In addition, we show that the precise timing of coincident CA3 and CA1 place cell spikes in relation to SWR onset is critical for the induction of LTP and predictive of plasticity generated by reactivation. Our findings confirm an important role for SWRs in triggering and tuning plasticity processes that underlie memory consolidation in the hippocampus during rest or sleep. PMID- 26904942 TI - Ezh2 Controls an Early Hematopoietic Program and Growth and Survival Signaling in Early T Cell Precursor Acute Lymphoblastic Leukemia. AB - Early T cell precursor acute lymphoblastic leukemia (ETP-ALL) is an aggressive subtype of ALL distinguished by stem-cell-associated and myeloid transcriptional programs. Inactivating alterations of Polycomb repressive complex 2 components are frequent in human ETP-ALL, but their functional role is largely undefined. We have studied the involvement of Ezh2 in a murine model of NRASQ61K-driven leukemia that recapitulates phenotypic and transcriptional features of ETP-ALL. Homozygous inactivation of Ezh2 cooperated with oncogenic NRASQ61K to accelerate leukemia onset. Inactivation of Ezh2 accentuated expression of genes highly expressed in human ETP-ALL and in normal murine early thymic progenitors. Moreover, we found that Ezh2 contributes to the silencing of stem-cell- and early progenitor-cell-associated genes. Loss of Ezh2 also resulted in increased activation of STAT3 by tyrosine 705 phosphorylation. Our data mechanistically link Ezh2 inactivation to stem-cell-associated transcriptional programs and increased growth/survival signaling, features that convey an adverse prognosis in patients. PMID- 26904943 TI - Dopamine Regulates Aversive Contextual Learning and Associated In Vivo Synaptic Plasticity in the Hippocampus. AB - Dopamine release during reward-driven behaviors influences synaptic plasticity. However, dopamine innervation and release in the hippocampus and its role during aversive behaviors are controversial. Here, we show that in vivo hippocampal synaptic plasticity in the CA3-CA1 circuit underlies contextual learning during inhibitory avoidance (IA) training. Immunohistochemistry and molecular techniques verified sparse dopaminergic innervation of the hippocampus from the midbrain. The long-term synaptic potentiation (LTP) underlying the learning of IA was assessed with a D1-like dopamine receptor agonist or antagonist in ex vivo hippocampal slices and in vivo in freely moving mice. Inhibition of D1-like dopamine receptors impaired memory of the IA task and prevented the training induced enhancement of both ex vivo and in vivo LTP induction. The results indicate that dopamine-receptor signaling during an aversive contextual task regulates aversive memory retention and regulates associated synaptic mechanisms in the hippocampus that likely underlie learning. PMID- 26904944 TI - A Long Non-coding RNA, lncLGR, Regulates Hepatic Glucokinase Expression and Glycogen Storage during Fasting. AB - Glucose levels in mammals are tightly controlled through multiple mechanisms to meet systemic energy demands. Downregulation of hepatic glucokinase (GCK) during fasting facilitates the transition of the liver from a glucose-consuming to a gluconeogenic organ. Here, we report the transcriptional regulation of hepatic GCK by a long non-coding RNA (lncRNA) named liver GCK repressor (lncLGR). lncLGR is induced by fasting, and physiological overexpression of lncLGR to mimic fasting levels effectively suppresses GCK expression and reduces hepatic glycogen content in mice. Consistently, lncLGR knockdown enhances GCK expression and glycogen storage in fasted mice. Mechanistically, lncLGR specifically binds to heterogenous nuclear ribonucleoprotein L (hnRNPL), which is further confirmed to be a transcriptional repressor of GCK in vivo. Finally, we demonstrate that lncLGR facilitates the recruitment of hnRNPL to the GCK promoter and suppresses GCK transcription. Our data establish a lncRNA-mediated mechanism that regulates hepatic GCK expression and glycogen deposition in a physiological context. PMID- 26904945 TI - c21orf59/kurly Controls Both Cilia Motility and Polarization. AB - Cilia are microtubule-based projections that function in the movement of extracellular fluid. This requires cilia to be: (1) motile and driven by dynein complexes and (2) correctly polarized on the surface of cells, which requires planar cell polarity (PCP). Few factors that regulate both processes have been discovered. We reveal that C21orf59/Kurly (Kur), a cytoplasmic protein with some enrichment at the base of cilia, is needed for motility; zebrafish mutants exhibit characteristic developmental abnormalities and dynein arm defects. kur was also required for proper cilia polarization in the zebrafish kidney and the larval skin of Xenopus laevis. CRISPR/Cas9 coupled with homologous recombination to disrupt the endogenous kur locus in Xenopus resulted in the asymmetric localization of the PCP protein Prickle2 being lost in mutant multiciliated cells. Kur also makes interactions with other PCP components, including Disheveled. This supports a model wherein Kur plays a dual role in cilia motility and polarization. PMID- 26904946 TI - Condensin Smc2-Smc4 Dimers Are Flexible and Dynamic. AB - Structural maintenance of chromosomes (SMC) protein complexes, including cohesin and condensin, play key roles in the regulation of higher-order chromosome organization. Even though SMC proteins are thought to mechanistically determine the function of the complexes, their native conformations and dynamics have remained unclear. Here, we probe the topology of Smc2-Smc4 dimers of the S. cerevisiae condensin complex with high-speed atomic force microscopy (AFM) in liquid. We show that the Smc2-Smc4 coiled coils are highly flexible polymers with a persistence length of only ~ 4 nm. Moreover, we demonstrate that the SMC dimers can adopt various architectures that interconvert dynamically over time, and we find that the SMC head domains engage not only with each other, but also with the hinge domain situated at the other end of the ~ 45-nm-long coiled coil. Our findings reveal structural properties that provide insights into the molecular mechanics of condensin complexes. PMID- 26904947 TI - MafA-Controlled Nicotinic Receptor Expression Is Essential for Insulin Secretion and Is Impaired in Patients with Type 2 Diabetes. AB - Monoamine and acetylcholine neurotransmitters from the autonomic nervous system (ANS) regulate insulin secretion in pancreatic islets. The molecular mechanisms controlling neurotransmitter signaling in islet beta cells and their impact on diabetes development are only partially understood. Using a glucose-intolerant, MafA-deficient mouse model, we demonstrate that MAFA controls ANS-mediated insulin secretion by activating the transcription of nicotinic (ChrnB2 and ChrnB4) and adrenergic (Adra2A) receptor genes, which are integral parts of acetylcholine- and monoamine-signaling pathways. We show that acetylcholine mediated insulin secretion requires nicotinic signaling and that nicotinic receptor expression is positively correlated with insulin secretion and glycemic control in human donor islets. Moreover, polymorphisms spanning MAFA-binding regions within the human CHRNB4 gene are associated with type 2 diabetes. Our data show that MAFA transcriptional activity is required for establishing beta cell sensitivity to neurotransmitter signaling and identify nicotinic signaling as a modulator of insulin secretion impaired in type 2 diabetes. PMID- 26904949 TI - RbAp46/48(LIN-53) Is Required for Holocentromere Assembly in Caenorhabditis elegans. AB - Centromeres, the specialized chromosomal regions for recruiting kinetochores and directing chromosome segregation, are epigenetically marked by a centromeric histone H3 variant, CENP-A. To maintain centromere identity through cell cycles, CENP-A diluted during DNA replication is replenished. The licensing factor M18BP1(KNL-2) is known to recruit CENP-A to holocentromeres. Here, we show that RbAp46/48(LIN-53), a conserved histone chaperone, is required for CENP-A(HCP-3) localization in holocentric Caenorhabditis elegans. Indeed, RbAp46/48(LIN-53) and CENP-A(HCP-3) localizations are interdependent. RbAp46/48(LIN-53) localizes to the centromere during metaphase in a CENP-A(HCP-3)- and M18BP1(KNL-2)-dependent manner, suggesting CENP-A(HCP-3) loading may occur before anaphase. RbAp46/48(LIN 53) does not function at the centromere through histone acetylation, H3K27 trimethylation, or its known chromatin-modifying complexes. RbAp46/48(LIN-53) may function independently to escort CENP-A(HCP-3) for holocentromere assembly but is dispensable for other kinetochore protein recruitment. Nonetheless, depletion of RbAp46/48(LIN-53) leads to anaphase bridges and chromosome missegregation. This study unravels the holocentromere assembly hierarchy and its conservation with monocentromeres. PMID- 26904948 TI - Autonomous Extracellular Matrix Remodeling Controls a Progressive Adaptation in Muscle Stem Cell Regenerative Capacity during Development. AB - Muscle stem cells (MuSCs) exhibit distinct behavior during successive phases of developmental myogenesis. However, how their transition to adulthood is regulated is poorly understood. Here, we show that fetal MuSCs resist progenitor specification and exhibit altered division dynamics, intrinsic features that are progressively lost postnatally. After transplantation, fetal MuSCs expand more efficiently and contribute to muscle repair. Conversely, niche colonization efficiency increases in adulthood, indicating a balance between muscle growth and stem cell pool repopulation. Gene expression profiling identified several extracellular matrix (ECM) molecules preferentially expressed in fetal MuSCs, including tenascin-C, fibronectin, and collagen VI. Loss-of-function experiments confirmed their essential and stage-specific role in regulating MuSC function. Finally, fetal-derived paracrine factors were able to enhance adult MuSC regenerative potential. Together, these findings demonstrate that MuSCs change the way in which they remodel their microenvironment to direct stem cell behavior and support the unique demands of muscle development or repair. PMID- 26904950 TI - Structural and Molecular Basis for Coordination in a Viral DNA Packaging Motor. AB - Ring NTPases are a class of ubiquitous molecular motors involved in basic biological partitioning processes. dsDNA viruses encode ring ATPases that translocate their genomes to near-crystalline densities within pre-assembled viral capsids. Here, X-ray crystallography, cryoEM, and biochemical analyses of the dsDNA packaging motor in bacteriophage phi29 show how individual subunits are arranged in a pentameric ATPase ring and suggest how their activities are coordinated to translocate dsDNA. The resulting pseudo-atomic structure of the motor and accompanying functional analyses show how ATP is bound in the ATPase active site; identify two DNA contacts, including a potential DNA translocating loop; demonstrate that a trans-acting arginine finger is involved in coordinating hydrolysis around the ring; and suggest a functional coupling between the arginine finger and the DNA translocating loop. The ability to visualize the motor in action illuminates how the different motor components interact with each other and with their DNA substrate. PMID- 26904951 TI - Early Developmental Program Shapes Colony Morphology in Bacteria. AB - When grown on a solid surface, bacteria form highly organized colonies, yet little is known about the earliest stages of colony establishment. Following Bacillus subtilis colony development from a single progenitor cell, a sequence of highly ordered spatiotemporal events was revealed. Colony was initiated by the formation of leading-cell chains, deriving from the colony center and extending in multiple directions, typically in a "Y-shaped" structure. By eradicating particular cells during these early stages, we could influence the shape of the resulting colony and demonstrate that Y-arm extension defines colony size. A mutant in ymdB encoding a phosphodiesterase displayed unordered developmental patterns, indicating a role in guiding these initial events. Finally, we provide evidence that intercellular nanotubes contribute to proper colony formation. In summary, we reveal a "construction plan" for building a colony and provide the initial molecular basis for this process. PMID- 26904952 TI - Structural and Functional Insights into the Unwinding Mechanism of Bacteroides sp Pif1. AB - Pif1 is a conserved SF1B DNA helicase involved in maintaining genome stability through unwinding double-stranded DNAs (dsDNAs), DNA/RNA hybrids, and G quadruplex (G4) structures. Here, we report the structures of the helicase domain of human Pif1 and Bacteroides sp Pif1 (BaPif1) in complex with ADP-AlF4(-) and two different single-stranded DNAs (ssDNAs). The wedge region equivalent to the beta hairpin in other SF1B DNA helicases folds into an extended loop followed by an alpha helix. The Pif1 signature motif of BaPif1 interacts with the wedge region and a short helix in order to stabilize these ssDNA binding elements, therefore indirectly exerting its functional role. Domain 2B of BaPif1 undergoes a large conformational change upon concomitant binding of ATP and ssDNA, which is critical for Pif1's activities. BaPif1 cocrystallized with a tailed dsDNA and ADP AlF4(-), resulting in a bound ssDNA bent nearly 90 degrees at the ssDNA/dsDNA junction. The conformational snapshots of BaPif1 provide insights into the mechanism governing the helicase activity of Pif1. PMID- 26904953 TI - Control of Smc Coiled Coil Architecture by the ATPase Heads Facilitates Targeting to Chromosomal ParB/parS and Release onto Flanking DNA. AB - Smc/ScpAB promotes chromosome segregation in prokaryotes, presumably by compacting and resolving nascent sister chromosomes. The underlying mechanisms, however, are poorly understood. Here, we investigate the role of the Smc ATPase activity in the recruitment of Smc/ScpAB to the Bacillus subtilis chromosome. We demonstrate that targeting of Smc/ScpAB to ParB/parS loading sites is strictly dependent on engagement of Smc head domains and relies on an open organization of the Smc coiled coils. We find that dimerization of the Smc hinge domain stabilizes closed Smc rods and hinders head engagement as well as chromosomal targeting. Conversely, the ScpAB sub-complex promotes head engagement and Smc rod opening and thereby facilitates recruitment of Smc to parS sites. Upon ATP hydrolysis, Smc/ScpAB is released from loading sites and relocates within the chromosome-presumably through translocation along DNA double helices. Our findings define an intermediate state in the process of chromosome organization by Smc. PMID- 26904954 TI - miR-137 Modulates a Tumor Suppressor Network-Inducing Senescence in Pancreatic Cancer Cells. AB - Activating K-Ras mutations occurs frequently in pancreatic cancers and is implicated in their development. Cancer-initiating events, such as oncogenic Ras activation, lead to the induction of cellular senescence, a tumor suppressor response. During senescence, the decreased levels of KDM4A lysine demethylase contribute to p53 activation, however, the mechanism by which KDM4A is downregulated is unknown. We show that miR-137 targets KDM4A mRNA during Ras induced senescence and activates both p53 and retinoblastoma (pRb) tumor suppressor pathways. Restoring the KDM4A expression contributed to bypass of miR 137-induced senescence and inhibition of endogenous miR-137 with an miRNA sponge compromised Ras-induced senescence. miR-137 levels are significantly reduced in human pancreatic tumors, consistent with previous studies revealing a defective senescence response in this cancer type. Restoration of miR-137 expression inhibited proliferation and promoted senescence of pancreatic cancer cells. These results suggest that modulating levels of miR-137 may be important for triggering tumor suppressor networks in pancreatic cancer. PMID- 26904955 TI - Hox Proteins Coordinate Motor Neuron Differentiation and Connectivity Programs through Ret/Gfralpha Genes. AB - The accuracy of neural circuit assembly relies on the precise spatial and temporal control of synaptic specificity determinants during development. Hox transcription factors govern key aspects of motor neuron (MN) differentiation; however, the terminal effectors of their actions are largely unknown. We show that Hox/Hox cofactor interactions coordinate MN subtype diversification and connectivity through Ret/Gfralpha receptor genes. Hox and Meis proteins determine the levels of Ret in MNs and define the intrasegmental profiles of Gfralpha1 and Gfralpha3 expression. Loss of Ret or Gfralpha3 leads to MN specification and innervation defects similar to those observed in Hox mutants, while expression of Ret and Gfralpha1 can bypass the requirement for Hox genes during MN pool differentiation. These studies indicate that Hox proteins contribute to neuronal fate and muscle connectivity through controlling the levels and pattern of cell surface receptor expression, consequently gating the ability of MNs to respond to limb-derived instructive cues. PMID- 26904956 TI - lncRNA-Induced Nucleosome Repositioning Reinforces Transcriptional Repression of rRNA Genes upon Hypotonic Stress. AB - The activity of rRNA genes (rDNA) is regulated by pathways that target the transcription machinery or alter the epigenetic state of rDNA. Previous work has established that downregulation of rRNA synthesis in quiescent cells is accompanied by upregulation of PAPAS, a long noncoding RNA (lncRNA) that recruits the histone methyltransferase Suv4-20h2 to rDNA, thus triggering trimethylation of H4K20 (H4K20me3) and chromatin compaction. Here, we show that upregulation of PAPAS in response to hypoosmotic stress does not increase H4K20me3 because of Nedd4-dependent ubiquitinylation and proteasomal degradation of Suv4-20h2. Loss of Suv4-20h2 enables PAPAS to interact with CHD4, a subunit of the chromatin remodeling complex NuRD, which shifts the promoter-bound nucleosome into the transcriptional "off" position. Thus, PAPAS exerts a "stress-tailored" dual function in rDNA silencing, facilitating either Suv4-20h2-dependent chromatin compaction or NuRD-dependent changes in nucleosome positioning. PMID- 26904957 TI - Primary mucinous carcinoma of the skin with in situ components on the cheek. PMID- 26904958 TI - Lipoic acid does not improve renal function markers in 5/6 nephrectomy model: possible role of Nrf2 inactivation. AB - Chronic kidney disease (CKD) progression and complications are associated with increased oxidative stress, as well as with Nrf2 inactivation. Lipoic acid (LA) has been considered an inducer of Nrf2 antioxidant response. We tested whether oral administration of LA provides beneficial effects in experimental CKD in rats. Wistar rats underwent 5/6 nephrectomy (CKD group) or sham laparotomy. Seven days later, CKD group was divided into three subgroups that received: (i) LA continuously in the drinking water (100 mg/kg/day), (ii) LA by gavage every other day (100 mg/kg), or (iii) no LA treatment. LA treatment lasted until day 60. Plasma urea and creatinine, 24 h-proteinuria, glomerulosclerosis, interstitial fibrosis/tubular atrophy, and Nrf2 activation were analyzed. All parameters measured were significantly altered in the untreated CKD group, compared with the sham group, as expected. Oral LA administration, either in the drinking water or by gavage, did not improve significantly any parameter, comparing the treated groups with the untreated CKD group. These results indicate that oral LA administration for 53 days was ineffective to reactivate Nrf2 in the remnant kidney of uremic rats, likely preventing improvements in biochemical and histopathological markers of renal function. PMID- 26904959 TI - Risk factors and burden of osteoarthritis. AB - Osteoarthritis (OA) is one of the most common joint disorders worldwide. Its prevalence is increasing because of the growing aging of the population in developed and developing countries as well as an increase in risk factors leading to OA, particularly obesity and a sedentary lifestyle. Risk factors of OA can be divided into person-level factors (age, gender, obesity, genetics and diet) and joint-level factors (injury, malalignment and abnormal loading of the joints) that interact in a complex manner. OA is the 11th cause of disability in the world. It is responsible for activity limitations, particularly walking, and affects participation and quality of life. Patients with OA are at greater risk of all-cause mortality, particularly for cardiovascular diseases, than the general population. This excess mortality is closely associated with disability level. Consequently, strategies to reduce burden through primary and secondary prevention programs are increasingly important. PMID- 26904960 TI - Anatomical specificities of the degenerated cervical spine: a narrative review of clinical implications, with special focus on targeted spinal injections. AB - BACKGROUND: Cervical radiculopathy is most often related to foraminal stenosis due to osteoarthritic changes of the uncovertebral joints anteriorly or zygapophyseal joints posteriorly, rather than disc herniation. OBJECTIVES: To describe anatomical specificities of the degenerated cervical spine. METHODS: A critical narrative review was conducted. Articles were non-systematically selected and based on authors' expertise, self-knowledge, and reflective practice. RESULTS: Vertebral bodies of the lower cervical spine are characterized by 2 lateral prismatic bony protuberances, the uncinate processes, located on C3 to C7 superior vertebral endplates, that are involved in the stabilization of the cervical spine. Degenerative changes at the lower cervical spine can affect different anatomical structures: the intervertebral disc, uncovertebral joints, and facet joints. The incidence and severity of changes increase with age. Furthermore, uncovertebral osteoarthritis is characterized by the presence of transverse fissures in the annulus fibrosus. DISCUSSION: These specific anatomical features of the cervical spine may have clinical implications, including more targeted spinal injections for managing disabling persistent or recurrent symptoms related to cervical spine degenerative changes such as cervical radicular pain. PMID- 26904961 TI - Isocryptotanshinone, a STAT3 inhibitor, induces apoptosis and pro-death autophagy in A549 lung cancer cells. AB - Signal transducer and activator of transcription 3 (STAT3) is a potential drug target for chemotherapy. Cryptotanshinone (CTS) was identified as a potent STAT3 inhibitor, while the effect of other tanshinones remains unknown. In this study, the influence of eight tanshinones on STAT3 activity was initially screened and isocryptotanshinone (ICTS) significantly inhibited STAT3 activity in a dual luciferase assay. ICTS inhibited the constitutive and inducible phosphorylation of STAT3 at Y705 without affecting the phosphorylation of STAT3 at S727 in A549 lung cancer cells. Furthermore, ICTS inhibited the nuclear translocation of STAT3. Compared with CTS, ICTS exhibited a stronger inhibitory effect on STAT3 phosphorylation and on A549 cytotoxicity. ICTS induced autophagy as evidenced by the accumulation of autophagic vacuoles and the increased expression of LC3 protein and autophagosomes. ICTS-induced cell death was partially reversed by the autophagy inhibitor chloroquine. The docking assay predicted that both ICTS and CTS bind the SH2 domain of STAT3. ICTS formed hydrogen bonds and pi-pi interaction with the nearby amino acid residues of Lys591, Arg609, and Ser636. These findings suggested that ICTS, a natural compound, is a potent STAT3 inhibitor. ICTS induced apoptosis and pro-death autophagy in A549 cells. PMID- 26904962 TI - Strategies for community-based medication management services in value-based health plans. AB - BACKGROUND: Health plans are moving away from a volume-driven payment structure toward value-driven and risk-based contracts. There is very limited information on commercial payers' perspectives on coverage of medication management services (MMS) in value-based alternative payment models. While some health plans have experience with Medicare Part D Medication Therapy Management (MTM) programs, this experience does not promote the integration of pharmacists as health care team members. OBJECTIVES: The study objectives were to: (1) understand the evaluation process that health plan executives would use to determine benefit coverage for pharmacist-provided MMS in value-based health plans, (2) identify the facilitators and barriers that affect pharmacist-provided MTM services at the community pharmacy level, and (3) propose strategies for pharmacist-provided MMS in value-based health plans. METHODS: This study used qualitative research methods that involved structured key informant interviews with commercial health plan executives and focus groups with community pharmacists who had experience providing MTM services. RESULTS: Health plan executives agreed conceptually that MMS could be a valuable program and recognized its potential. However, the most substantial barriers that health plan executives expressed were funding MMS in today's fee-for-service payment models; lack of physician infrastructure to implement and manage MMS; and difficulty in collecting timely, accurate data to execute and assess MMS programs. Community pharmacists identified the most serious barrier to altering health outcomes through MTM as the current lack of integration of MTM with a coordinated health care team. MTM services are conducted as a separate program by pharmacists who do not have access to patient health records, are time-constrained, and poorly incentivized. CONCLUSIONS: The findings can inform the development of successful strategies for pharmacist provided MMS that align with emerging value-based health plans and alternative provider payment models. Current MTM program barriers and facilitators are identified that could be addressed in future Part D MTM program policy changes. PMID- 26904965 TI - Severe Nausea and Vomiting in the Evaluation of Nitrous Oxide in the Gas Mixture for Anesthesia II Trial. AB - BACKGROUND: The Evaluation of Nitrous oxide in the Gas Mixture for Anesthesia II trial randomly assigned 7,112 noncardiac surgery patients to a nitrous oxide or nitrous oxide-free anesthetic; severe postoperative nausea and vomiting (PONV) was a prespecified secondary end point. Thus, the authors evaluated the association between nitrous oxide, severe PONV, and effectiveness of PONV prophylaxis in this setting. METHODS: Univariate and multivariate analyses of patient, surgical, and other perioperative characteristics were used to identify the risk factors for severe PONV and to measure the impact of severe PONV on patient outcomes. RESULTS: Avoiding nitrous oxide reduced the risk of severe PONV (11 vs. 15%; risk ratio [RR], 0.74 [95% CI, 0.63 to 0.84]; P < 0.001), with a stronger effect in Asian patients (RR, 0.55 [95% CI, 0.43 to 0.69]; interaction P = 0.004) but lower effect in those who received PONV prophylaxis (RR, 0.89 [95% CI, 0.76 to 1.05]; P = 0.18). Gastrointestinal surgery was associated with an increased risk of severe PONV when compared with most other types of surgery (P < 0.001). Patients with severe PONV had lower quality of recovery scores (10.4 [95% CI, 10.2 to 10.7] vs. 13.1 [95% CI, 13.0 to 13.2], P < 0.0005); severe PONV was associated with postoperative fever (15 vs. 20%, P = 0.001). Patients with severe PONV had a longer hospital stay (adjusted hazard ratio, 1.14 [95% CI, 1.05 to 1.23], P = 0.002). CONCLUSIONS: The increased risk of PONV with nitrous oxide is near eliminated by antiemetic prophylaxis. Severe PONV, which is seen in more than 10% of patients, is associated with postoperative fever, poor quality of recovery, and prolonged hospitalization. PMID- 26904966 TI - A randomized controlled trial of mother-infant psychoanalytic treatment: II. Predictive and moderating influences of qualitative patient factors. AB - A randomized control trial was performed on 75 dyads in Stockholm, Sweden, with infants under 11/2 years. It recruited mothers who worried about the babies, themselves as mothers, and/or the mother-baby relationship. Two groups of mother infant dyads were compared. One received only Child Health Centre care (the "CHCC" group) while the other received mother-infant psychoanalytic treatment plus CHCC (the "MIP" group). Significant treatment effects were found on mother reported depression, interviewer-rated dyadic relationship qualities and externally rated maternal sensitivity, and near-significant effects on mother reported stress, all in favor of MIP. The objective of this study is to investigate the predictive and moderating influences on outcomes by qualitatively assessed maternal and infant characteristics. The qualitative factors covered maternal suitability for psychoanalysis, and "ideal types" of mother and child, respectively. Outcome measures from two interviews with a 6-month interval were depression (Edinburgh Postnatal Depression Scale (J. Cox, J. Holden, & R. Sagovsky, 1987), stress (Swedish Parental Stress Questionnaire (M. Ostberg, B. Hagekull, & S. Wettergren, 1997), distress (Swedish Symptom Checklist-90 (SCL-90; L.R. Derogatis, 1994; M. Fridell, Z. Cesarec, M. Johansson, & S. Malling Thorsen, 2002) and infant social and emotional functioning (Ages and Stages Questionnaire: Social-Emotional (J. Squires, D. Bricker, K. Heo, & E. Twombly, 2002), relationship qualities (Parent-Infant Global Assessment Scale (PIR-GAS; ZERO TO THREE, 2005), and videotaped interactions (Emotional Availability Scales, Z. Biringen, J.L. Robinson, & R.N. Emde, 1998). Suitability for psychoanalysis predicted outcome only on the PIR-GAS. Two overarching maternal ideal types were created, reflecting their attitude to the psychoanalytic process: "Participators" and "Abandoned." The Participators benefited more from MIP than they did from CHCC on maternal interactive sensitivity. A contrasting, but nonsignificant, pattern was found among the Abandoned mothers. Two ideal types of babies emerged: those "Affected" and "Unaffected" by the disturbance, respectively. Among Affected babies, dyadic relationships and sensitivity among their mothers improved significantly more from MIP than they did from CHCC. The superior effects of MIP applied especially to Participator mothers and Affected infants. For Abandoned mothers and Unaffected infants, CHCC seemed to be of equal value. PMID- 26904963 TI - Human oocyte developmental potential is predicted by mechanical properties within hours after fertilization. AB - The causes of embryonic arrest during pre-implantation development are poorly understood. Attempts to correlate patterns of oocyte gene expression with successful embryo development have been hampered by the lack of reliable and nondestructive predictors of viability at such an early stage. Here we report that zygote viscoelastic properties can predict blastocyst formation in humans and mice within hours after fertilization, with >90% precision, 95% specificity and 75% sensitivity. We demonstrate that there are significant differences between the transcriptomes of viable and non-viable zygotes, especially in expression of genes important for oocyte maturation. In addition, we show that low-quality oocytes may undergo insufficient cortical granule release and zona hardening, causing altered mechanics after fertilization. Our results suggest that embryo potential is largely determined by the quality and maturation of the oocyte before fertilization, and can be predicted through a minimally invasive mechanical measurement at the zygote stage. PMID- 26904967 TI - Real-Time Control of a Neuroprosthetic Hand by Magnetoencephalographic Signals from Paralysed Patients. AB - Neuroprosthetic arms might potentially restore motor functions for severely paralysed patients. Invasive measurements of cortical currents using electrocorticography have been widely used for neuroprosthetic control. Moreover, magnetoencephalography (MEG) exhibits characteristic brain signals similar to those of invasively measured signals. However, it remains unclear whether non invasively measured signals convey enough motor information to control a neuroprosthetic hand, especially for severely paralysed patients whose sensorimotor cortex might be reorganized. We tested an MEG-based neuroprosthetic system to evaluate the accuracy of using cortical currents in the sensorimotor cortex of severely paralysed patients to control a prosthetic hand. The patients attempted to grasp with or open their paralysed hand while the slow components of MEG signals (slow movement fields; SMFs) were recorded. Even without actual movements, the SMFs of all patients indicated characteristic spatiotemporal patterns similar to actual movements, and the SMFs were successfully used to control a neuroprosthetic hand in a closed-loop condition. These results demonstrate that the slow components of MEG signals carry sufficient information to classify movement types. Successful control by paralysed patients suggests the feasibility of using an MEG-based neuroprosthetic hand to predict a patient's ability to control an invasive neuroprosthesis via the same signal sources as the non-invasive method. PMID- 26904969 TI - Erratum: "The Effect of Subepithelial Connective Tissue Graft Placement on Esthetic Outcomes After Immediate Implant Placement: Systematic Review". PMID- 26904968 TI - The experience of setting up a resident-managed Acute Pain Service: a descriptive study. AB - BACKGROUND: The benefits of an Acute Pain Service (APS) for pain management have been widely reported, but its diffusion is still limited. There are two APS models: anesthesiologist-based and a nurse-based model. Here we describe the development of a different APS model managed by anesthesia residents, and we report the first year of activity in a tertiary Italian university hospital (Careggi University Hospital, Florence, IT). METHODS: Patients were included in the APS were those undergoing abdominal and urologic surgery causing moderate or severe postsurgical pain. The service was provided for patients, beginning upon their exit from the operating room, for 4, 12, 24 and 48 h for iv, and up to 72 h for epidural therapy. Vital signs, static/dynamic VAS, presence of nausea/vomiting, sedation level, and Bromage scale in case of epidural catheter, were monitored. RESULTS: From September 2013 to April 2015, a total of 1054 patients who underwent major surgery were included in the APS: 542 from abdominal surgery and 512 from urological surgery. PCA and epidural analgesia were more adopted in general surgical patients than in urology (48% vs 36% and 15% vs 2%, respectively; P < 0.0001). Patients who underwent to abdominal surgery had a significantly higher self-administration of morphine (30.3 vs 22.7 mg; P = 0.0315). Elastomeric pump was the analgesic of choice in half of the urologic patients compared to a quarter of the general surgical patients (P < .0001). Among the different surgical techniques, epidural analgesia was used more in open (16.5%) than in videolaparoscopic (1.9%) and robotic technique (1.1%), whereas PCA was predominant in videolaparoscopic (46.5%) and robotic technique (55.5%) than in open technique (31.4%). CONCLUSIONS: The creation of APS, managed by anesthesia residents, may represent an alternative between specialist-based and nurse-based models. PMID- 26904970 TI - Biphasic versus monophasic waveforms for transthoracic defibrillation in out-of hospital cardiac arrest. AB - BACKGROUND: Transthoracic defibrillation is a potentially life-saving treatment for people with ventricular fibrillation (VF) and haemodynamically unstable ventricular tachycardia (VT). In recent years, biphasic waveforms have become more commonly used for defibrillation than monophasic waveforms. Clinical trials of internal defibrillation and transthoracic defibrillation of short-duration arrhythmias of up to 30 seconds have demonstrated the superiority of biphasic waveforms over monophasic waveforms. However, out-of-hospital cardiac arrest (OHCA) involves a duration of VF/VT of several minutes before defibrillation is attempted. OBJECTIVES: To determine the efficacy and safety of biphasic defibrillation waveforms, compared to monophasic, for resuscitation of people experiencing out-of-hospital cardiac arrest. SEARCH METHODS: We searched the following electronic databases for potentially relevant studies up to 10 September 2014: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE. Also we checked the bibliographies of relevant studies and review articles, contacted authors of published reviews and reviewed webpages (including those of device manufacturers) relevant to the review topic. We handsearched the abstracts of conference proceedings for the American Heart Association, American College of Cardiology, European Society of Cardiology, European Resuscitation Council, Society of Critical Care Medicine and European Society of Intensive Care Medicine. Regarding language restrictions, we did not apply any. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared biphasic and monophasic waveform defibrillation in adults with OHCA. Two review authors independently screened the literature search results. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from the included trials and performed 'Risk of bias' assessments. We resolved any disagreements by discussion and consensus. The primary outcome was the risk of failure to achieve return of spontaneous circulation (ROSC). Secondary outcomes included risk of failure to revert VF to an organised rhythm following the first shock or up to three shocks, survival to hospital admission and survival to discharge. MAIN RESULTS: We included four trials (552 participants) that compared biphasic and monophasic waveform defibrillation in people with OHCA. Based on the assessment of five quality domains, we identified two trials that were at high risk of bias, one trial at unclear risk of bias and one trial at low risk of bias. The risk ratio (RR) for failure to achieve ROSC after biphasic compared to monophasic waveform defibrillation was 0.86 (95% CI 0.62 to 1.20; four trials, 552 participants). The RR for failure to defibrillate on the first shock following biphasic defibrillation compared to monophasic was 0.84 (95% CI 0.70 to 1.01; three trials, 450 participants); and 0.81 (95% CI 0.61 to 1.09; two trials, 317 participants) for one to three stacked shocks. The RR for failure to achieve ROSC after the first shock was 0.92 (95% CI 0.81 to 1.04; two trials, 285 participants). Biphasic waveforms did not reduce the risk of death before hospital admission (RR 1.05, 95% CI 0.90 to 1.23; three trials, 383 participants) or before hospital discharge (RR 1.05, 95% CI 0.78 to 1.42; four trials, 550 participants). There was no statistically significant heterogeneity in any of the pooled analyses. None of the included trials reported adverse events. AUTHORS' CONCLUSIONS: It is uncertain whether biphasic defibrillators have an important effect on defibrillation success in people with OHCA. Further large studies are needed to provide adequate statistical power. PMID- 26904971 TI - [Effectiveness of management of children with severe trauma in a pediatric trauma center and in an adult trauma center: A before-after study]. AB - OBJECTIVE: To compare management of injured children in an adult trauma center (TC) with competencies in pediatric trauma care (2005-2007) and in a pediatric only trauma center (2010-2012). STUDY DESIGN: A before-after retrospective study. PATIENTS AND METHODS: Fifty-nine children between 1 and 15 years of age admitted to the adult TC (2005-2007) were compared to 56 children admitted to the pediatric TC (2010-2012). Epidemiological data, severity scores, early outcome, and care duration in trauma resuscitation before whole-body CT were collected and compared between the two periods. RESULTS: This study found no significant differences between the two periods in terms of care duration before the whole body CT scan (28 min [18-40] vs 26.5 min [21-36], P=0.89) and early mortality (eight children [13.5%] vs ten children [17.8%], P=0.35). CONCLUSION: With no differences in early management of injured children demonstrated, this study validates the organization within our pediatric trauma center. The effectiveness of management of children between 1 and 15 years of age with severe trauma seems to be similar in the two contexts. PMID- 26904972 TI - DAS181 for Treatment of Parainfluenza Virus Infections in Hematopoietic Stem Cell Transplant Recipients at a Single Center. AB - Parainfluenza virus (PIV) causes severe respiratory infections in hematopoietic stem cell transplant (HSCT) recipients. Currently, no effective therapies are available. DAS181 is a novel antiviral agent that inhibits attachment of PIV to respiratory cells, but clinical data on the use of DAS181 for PIV infection are limited to case reports. We report the clinical manifestations and outcomes of 16 HSCT recipients who received DAS181 daily for the treatment of PIV infection through a compassionate-use protocol or a single-arm clinical trial. Of the 16 patients (clinical trial: 9; compassionate use: 7), 13 were allogeneic HSCT recipients and 8 had graft-versus-host disease. PIV types were 3 (n = 7), 4 (n = 5), 1 (n = 3), and type 3 and 4 coinfection (n = 1). Fourteen patients had pneumonia. All patients presented with cough, 14 had dyspnea, 11 had hypoxia, and 8 had a fever. Patients received 5 to 10 days of treatment. Nine patients (56%) had a complete clinical response after DAS181 therapy and 4 (25%) had a partial response. The 3 patients without a clinical response had coinfections with other pathogens. Of the 7 patients with virologic and spirometric data, 5 had >1-log reduction in nasopharyngeal swab PIV viral load and 4 had improved forced expiratory volumes by the end of treatment. Three patients (19%) died within 30 days and 2 of these deaths were related to PIV infection. Our data suggest that DAS181 may be an effective therapy for PIV pneumonia in HSCT recipients. Randomized placebo-controlled trials are needed to better evaluate its efficacy. PMID- 26904973 TI - Differentiating technical skill and motor abilities in selected and non-selected 3-5 year old team-sports players. AB - This study examined the difference in 22 3-5year old boys selected to an advanced or non-advanced group on an English community-based professional club training program. Time to complete 15m linear sprint and 15m zig-zag agility tests, with and without a ball, were used to assess the children's technical skill and motor ability. Age and body mass of both groups were the same, whereas height was greater and BMI was lower in the selected group (p<0.01). Linear sprint times without and with the ball were 3.98+/-0.35 and 4.44+/-0.36s, respectively for the selected and corresponding times were 4.64+/-1.04 and 11.2+/-5.37s for the non selected (p<0.01, ES 0.8, 1.8). Similar results were found when a change of movement was included, both with and without the ball. A model of selection indicated that performance in an agility test with the ball and height had the greatest discriminatory power and explained 95.5% of between group variance. Selected players performed significantly better in tests when ball control was required. These findings suggest that technical proficiency and physical differences may influence team selection in three to five year old children. PMID- 26904974 TI - Effects of short-term fatigue on biomechanical and physiological aspects of double poling in high-level cross-country skiers. AB - The study aim was to evaluate biomechanical and physiological alterations in double poling technique (DP) after a short-term fatiguing exercise. Eight high level skiers performed a sub-maximal DP trial (20kmh(-1), 1 degrees ) before (PRE) and after (POST) a DP test to exhaustion while roller skiing on a treadmill. An integrated analysis of DP technique during PRE and POST included measurement of pole, joint, and centre of mass (COM) kinematics, poling forces, cycle timing, and metabolic parameters. Muscle fatigue in three upper-body muscles was assessed by calculating the Dimitrov' fatigue index (FInms5) of specific electromyographic segments. FInms5 tended to increase in the latissimus dorsi and teres major muscles (P=0.023 and P=0.030, respectively) across consecutive DP cycles, as did blood lactate concentration (P=0.001) and rating of perceived exertion (P=0.005). The changes indicated a state of fatigue during POST and coincided with the reduction in poling force exertion capacity (P=0.020). Pole, joint and COM kinematics did not differ between PRE and POST (P>0.050), whereas recovery phase and cycle times were shorter at POST (P<0.001 and P=0.001, respectively). Short-term fatigue led to a reduction in poling force exertion capacity and cycle time in high-level skiers, without altering body and pole kinematics. PMID- 26904975 TI - Long-term clinical outcome of Budd-Chiari syndrome in children after radiological intervention. AB - OBJECTIVES: Budd-Chiari syndrome (BCS) is an uncommon cause of chronic liver disease in children. The literature on the management of pediatric BCS is scarce. Our aim was to determine the long-term outcome of patients undergoing a radiological intervention for the treatment of BCS. METHODS: Thirty-two children diagnosed with BCS between 2004 and 2014 were included. Data on the course of disease, medical management, response, and complications related to radiological interventions and outcome were collected. MAIN RESULTS: Twenty-five patients who were on regular follow-up were analyzed. The median age of the patients at presentation was 9 months (4.5-214). Sixteen patients initially received anticoagulation alone. This was associated with a high failure rate of 66%. Twenty patients underwent a radiological intervention in the form of angioplasty (n=7), hepatic vein stenting (n=3) or transjugular intrahepatic portosystemic shunt (TIPS) (n=14). Success with angioplasty was achieved in 43% of cases. Hepatic vein stenting was successful in 66%, whereas TIPS was successful in 72% of cases. TIPS was feasible in all patients. The median follow-up duration was 44 months (5-132). Four patients developed hepatopulmonary syndrome after a median period of 3 years (1.5-5.25) and one patient developed hepatocellular carcinoma. CONCLUSION: BCS commonly presents during infancy. Anticoagulation alone and angioplasty of the hepatic veins are associated with a high failure rate. Hepatic vein stenting or TIPS is feasible and efficacious in improving liver function, portal hypertension, and growth. It is associated with good long-term outcome and delays the need for liver transplantation, but may not prevent complications such as hepatopulmonary syndrome and hepatocellular carcinoma. PMID- 26904976 TI - Inadequate seroprotection against hepatitis B virus and one detected case of hepatitis C virus infection among patients with inflammatory bowel disease. AB - OBJECTIVES: The prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections among patients with inflammatory bowel disease (IBD) from central and eastern European countries is unknown. Postvaccination HBV immunity in an immunocompromised host may wane. The aims of the study were as follows: to assess the immune status for HBV and HCV among IBD patients, the level of HBV seroprotection, and to compare the immune status of patients who received mandatory versus recommended HBV vaccination. MATERIALS AND METHODS: Serological markers of HBV and HCV (anti-HBs, anti-HBc, HBsAg, and anti-HCV) were determined in 147 consecutive IBD patients. An anti-HBs of 10 IU/l or more was considered as immunity to HBV infection. RESULTS: HBV infection was detected in 21 patients, whereas 11 of them recalled previous HBV vaccination. Sixty-eight noninfected patients had a level of anti-HBs 10 IU/l or more and only 29% reached the cut-off level of 100 IU/l. Among patients vaccinated obligatorily, two patients had previous HBV infection and 15% did not have an adequate seroprotection against HBV. Patients who received a mandatory HBV vaccine more frequently had a protective anti-HBs level than those vaccinated voluntarily (P<0.001). One positive anti-HCV result was found. CONCLUSION: A mandatory HBV vaccination significantly increased the number of patients effectively protected against HBV; however, a remarkable number of vaccinated IBD patients had inadequate HBV seroprotection. All IBD patients should be screened for HBV and HCV infections and monitored for anti-HBs titers. PMID- 26904977 TI - What is a clinical pathway? Refinement of an operational definition to identify clinical pathway studies for a Cochrane systematic review. AB - Clinical pathways (CPWs) are a common component in the quest to improve the quality of health. CPWs are used to reduce variation, improve quality of care, and maximize the outcomes for specific groups of patients. An ongoing challenge is the operationalization of a definition of CPW in healthcare. This may be attributable to both the differences in definition and a lack of conceptualization in the field of clinical pathways. This correspondence article describes a process of refinement of an operational definition for CPW research and proposes an operational definition for the future syntheses of CPWs literature. Following the approach proposed by Kinsman et al. (BMC Medicine 8(1):31, 2010) and Wieland et al. (Alternative Therapies in Health and Medicine 17(2):50, 2011), we used a four-stage process to generate a five criteria checklist for the definition of CPWs. We refined the operational definition, through consensus, merging two of the checklist's criteria, leading to a more inclusive criterion for accommodating CPW studies conducted in various healthcare settings. The following four criteria for CPW operational definition, derived from the refinement process described above, are (1) the intervention was a structured multidisciplinary plan of care; (2) the intervention was used to translate guidelines or evidence into local structures; (3) the intervention detailed the steps in a course of treatment or care in a plan, pathway, algorithm, guideline, protocol or other 'inventory of actions' (i.e. the intervention had time-frames or criteria-based progression); and (4) the intervention aimed to standardize care for a specific population. An intervention meeting all four criteria was considered to be a CPW. The development of operational definitions for complex interventions is a useful approach to appraise and synthesize evidence for policy development and quality improvement. PMID- 26904978 TI - Period-independent novel circadian oscillators revealed by timed exercise and palatable meals. AB - The mammalian circadian system is a hierarchical network of oscillators organized to optimally coordinate behavior and physiology with daily environmental cycles. The suprachiasmatic nucleus (SCN) of the hypothalamus is at the top of this hierarchy, synchronizing to the environmental light-dark cycle, and coordinates the phases of peripheral clocks. The Period genes are critical components of the molecular timekeeping mechanism of these clocks. Circadian clocks are disabled in Period1/2/3 triple mutant mice, resulting in arrhythmic behavior in constant conditions. We uncovered rhythmic behavior in this mutant by simply exposing the mice to timed access to a palatable meal or running wheel. The emergent circadian behavior rhythms free-ran for many cycles under constant conditions without cyclic environmental cues. Together, these data demonstrate that the palatable meal-inducible circadian oscillator (PICO) and wheel-inducible circadian oscillator (WICO) are generated by non-canonical circadian clocks. Entrainment of these novel oscillators by palatable snacks and timed exercise could become novel therapeutics for human conditions caused by disruptions of the circadian clocks. PMID- 26904980 TI - Preface: The Eye and The Chip world research congress on visual neuro prosthetics. PMID- 26904979 TI - Evolution of resistance to cationic biocides in Streptococcus mutans and Enterococcus faecalis. AB - OBJECTIVES: The aim of this study was to investigate whether Streptococcus mutans and Enterococcus faecalis develop resistance to the cationic biocides chlorhexidine (CHX), cetylpyridinium chloride (CPC), and 12 methacryloyloxydodecylpyridinium bromide (MDPB). METHODS: The minimum inhibitory concentrations (MICs) of CHX, CPC, and MDPB were assessed after repeated exposure of S. mutans and E. faecalis to these biocides. Cell-surface hydrophobicity and protein expression profiles of bacterial cells were examined to elucidate possible resistance mechanisms. RESULTS: The MIC of CHX against E. faecalis showed constant increases up to 10 passages. No changes in the MICs of CPC and MDPB against E. faecalis were observed. The MICs of CHX, CPC, and MDPB against S. mutans did not increase. The surface hydrophobicity of E. faecalis significantly increased with increasing exposure to CHX and CPC. However, changes in protein expression profiles were only found in CHX-adapted E. faecalis, as evidenced by the emergence of a novel, approximately 19-kDa band following sodium dodecyl sulfate-polyacrylamide gel electrophoresis. CONCLUSIONS: While E. faecalis and S. mutans did not exhibit increased resistance to CPC or MDPB, repeated exposure of E. faecalis to CHX led to resistance. It is likely that the acquisition of resistance is related to an altered protein composition. CLINICAL SIGNIFICANCE: Alkyl pyridinium compounds, such as CPC and MDPB, could have a lower risk to cause adaptation of E. faecalis, which is advantageous compared with CHX. PMID- 26904982 TI - Randomized Comparison of the Crush Versus the Culotte Stenting for Coronary Artery Bifurcation Lesions. AB - BACKGROUND: The crush and the culotte stenting were both reported to be effective for complex bifurcation lesion treatment. However, their comparative performance remains elusive. METHODS: A total of 300 patients with coronary bifurcation lesions were randomly assigned to crush (n = 150) and culotte (n = 150) treatment. The primary endpoint was the occurrence of major adverse cardiac events (MACEs) at 12 months including cardiac death, myocardial infarction, stent thrombosis, and target vessel revascularization. Index lesion restenosis at 12 months was a secondary endpoint. The surface integrals of time-averaged wall shear stress at bifurcation sites were also be quantified. RESULTS: There were no significant differences in MACE rates between the two groups at 12-month follow up: Crush 6.7%, culotte 5.3% (P = 0.48). The rates of index lesion restenosis were 12.7% versus 6.0% (P = 0.047) in the crush and the culotte groups, respectively. At 12-month follow-up, the surface integrals of time-averaged wall shear stress at bifurcation sites in the crush group were significantly lower than the culotte group ([5.01 +/- 0.95] * 10-4 Newton and [6.08 +/- 1.16] * 10-4 Newton, respectively; P = 0.003). CONCLUSIONS: Both the crush and the culotte bifurcation stenting techniques showed satisfying clinical and angiographic results at 12-month follow-up. Bifurcation lesions treated with the culotte technique tended to have lower restenosis rates and more favorable flow patterns. PMID- 26904981 TI - Lipid profiles of detergent resistant fractions of the plasma membrane in oat and rye in association with cold acclimation and freezing tolerance. AB - Cold acclimation (CA) results in alteration of the plasma membrane (PM) lipid composition in plants, which plays a crucial role in the acquisition of freezing tolerance via membrane stabilization. Recent studies have indicated that PM structure is consistent with the fluid mosaic model but is laterally non homogenous and contains microdomains enriched in sterols, sphingolipids and specific proteins. In plant cells, the function of these microdomains in relation to CA and freezing tolerance is not yet fully understood. The present study aimed to investigate the lipid compositions of detergent resistant fractions of the PM (DRM) which are considered to represent microdomains. They were prepared from leaves of low-freezing tolerant oat and high-freezing tolerant rye. The DRMs contained higher proportions of sterols, sphingolipids and saturated phospholipids than the PM. In particular, one of the sterol lipid classes, acylated sterylglycoside, was the predominant sterol in oat DRM while rye DRM contained free sterol as the major sterol. Oat and rye showed different patterns (or changes) of sterols and 2-hydroxy fatty acids of sphingolipids of DRM lipids during CA. Taken together, these results suggest that CA-induced changes of lipid classes and molecular species in DRMs are associated with changes in the thermodynamic properties and physiological functions of microdomains during CA and hence, influence plant freezing tolerance. PMID- 26904983 TI - Inverted Internal Limiting Membrane Flap Technique for Repair of Large Macular Holes: A Short-term Follow-up of Anatomical and Functional Outcomes. AB - BACKGROUND: Inverted internal limiting membrane (ILM) flap technique has recently been reported in a limited number of studies as an effective surgical technique for the management of large macular holes (MHs) with fair MH closure rates as well as gains in visual acuity. In the current study, longitudinal changes in multi-focal electroretinogram (mfERG) responses, best-corrected visual acuity (BCVA) and spectral-domain optical coherence tomography (SD-OCT) were evaluated in eyes with large MHs managed by this technique. METHODS: A prospective noncontrolled interventional study of eight patients (eight eyes) with large MHs (minimum diameter >400 MUm) was conducted. All MHs were treated with pars plana vitrectomy and indocyanine green-assisted inverted ILM flap technique. SD-OCT images were used to assess the anatomical outcomes of surgery while BCVA and mfERG were used to evaluate the functional outcomes during a 3-month follow-up. RESULTS: All patients underwent successful intended manipulation and translocation of the ILM flap without flap dislocation and achieved complete anatomical closure. Partial microstructural reconstruction, demonstrated on SD OCT as restoration of the external limiting membrane and the ellipsoid zone, was observed in all cases as early as 1 month after surgery. Functionally, as compared to baseline, all patients showed improvements in BCVA and all but one in mfERG response during follow-up. However, Pearson's test revealed no significant correlations between BCVA and mfERG responses of the fovea and of the macular area at each evaluation time point. CONCLUSIONS: Inverted ILM flap technique appears to be a safe and effective approach for the management of large idiopathic MHs with favorable short-term anatomical and functional results. Postoperative reconstruction of the microstructure generally shows good consistency with improvements in both BCVA and mfERG response, of which the latter might be a supplement for the former in postoperative functional follow up. PMID- 26904984 TI - Short-term Prognosis of Fragmented QRS Complex in Patients with Non-ST Elevated Acute Myocardial Infarction. AB - BACKGROUND: There remains significant debate as to the relationship between fragmented QRS (fQRS) complexes on electrocardiogram (ECG) and acute myocardial infarction (AMI). Few studies have reported on this relationship in non-ST elevated AMI (NSTEMI), and thus, we attempt to assess this relationship and its potential short-term prognostic value. METHODS: This was a single-center, observational, retrospective cohort study. A total of 513 consecutive patients (399 men, 114 women) with NSTEMI within 24 h who underwent coronary angiography at our department, between January 1, 2014, and December 31, 2014. Patients were divided into 2 groups according to the presence or absence of fQRS complex on the admission ECG. fQRS complexes were defined as the existence of an additional R' or crochetage wave, notching in the nadir of the S wave, RS fragmentation, or QS complexes on 2 contiguous leads. All patients were followed up for 6 months, and all major adverse cardiac events (MACE) were recorded. RESULTS: In this study, there were 285 patients with fQRS ECG in the 513 patients with NSTEMI. The number of patients with 0-2 coronary arteries narrowed by >=50% in fQRS group were less while patients with 3 narrowed arteries were more than in the non-fQRS group (P = 0.042). There were fewer Killip Class I patients in the fQRS group (P = 0.019), while Killip Class II, III, and IV patients were more in the fQRS group than in the non-fQRS group (P = 0.019). Left ventricular ejection fraction levels were significantly lower in the fQRS group (P = 0.021). Baseline total cholesterol, low-density lipoprotein, creatinine, creatine kinase, homocysteine, high sensitivity C-reactive protein (CRP), and red blood cells distribution width levels were significantly higher in the fQRS group. Total MACE (MACE, P = 0.028), revascularization (P = 0.005), and recurrent angina (P = 0.005) were also significantly greater in the fQRS group. On final logistic regression analysis, after adjusting for baseline variables, the following variables were independent predictors of fQRS: Coronary artery narrowing (P = 0.035), Killip classification (P = 0.026), and total cholesterol (P = 0.002). The following variables were found to be independent predictors of preoperative MACE: Hemoglobin (P = 0.000), gender (P = 0.026), fQRS (P = 0.016), and time from myocardial infarction to balloon or coronary artery bypasses grafting (P = 0.013). CONCLUSIONS: The fQRS complexes are commonly present in NSTEMI and the fQRS complexes are an independent predictor of MACE in NSTEMI patients. The number of narrowed coronary arteries, Killip classification, and total cholesterol are all independent predictors of the fQRS complexes. PMID- 26904985 TI - Behavioral Risk Profile of Men Who Have Sex with Men in Beijing, China: Results from a Cross-sectional Survey with Randomized Response Techniques. AB - BACKGROUND: Human immunodeficiency virus (HIV) is spreading rapidly among men who have sex with men (MSM) in China. Anonymous questionnaires or direct interviews have been frequently used to study their behavior. The aim of the study was to describe the behavioral risk profile of the MSM in Beijing using the randomized response techniques (RRTs). METHODS: A cross-sectional survey of sexual behavior among a sample of MSM was conducted in two HIV counseling and testing clinics in Beijing. The survey was carried out with an anonymous questionnaire containing sensitive questions on sexual behavior. To obtain the honest responses to the sensitive questions, three distinctive RRTs were used in the questionnaire: (1) Additive randomized response model for quantitative questions, (2) randomized response model for multiple choice questions, and (3) Simmons randomized response model for binomial questions. Formulae for the point estimate, variance, and confidence interval (CI) were provided for each specific model. RESULTS: Using RRTs in a sample of 659 participants, the mean age at first homosexual encounter was estimated to be 21.7 years (95% CI: 21.2-22.2), and each had sex with about three (2.9, 95% CI: 2.4-3.4) male partners on average in the past month. The estimated rate for consistent condom use was 56.4% (95% CI: 50.1-62.8%). In addition, condom was estimated to be used among 80.0% (95% CI: 74.1-85.9%) of the population during last anal sex with a male partner. CONCLUSIONS: Our study employed RRTs in a survey containing questions on sexual behavior among MSM, and the results showed that RRT might be a useful tool to obtain truthful feedback on sensitive information such as sexual behavior from the respondents, especially in traditional Chinese cultural settings. PMID- 26904986 TI - Impact of Cytoreductive Nephrectomy on Survival in Patients with Metastatic Renal Cell Carcinoma Treated by Targeted Therapy. AB - BACKGROUND: The metastatic renal cell carcinoma (mRCC) patients treated with upfront cytoreductive nephrectomy combined with alpha-interferon yields additional overall survival (OS) benefits. It is unclear whether mRCC patients treated with vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFR-TKI) will benefit from such cytoreductive nephrectomy either. The aim of the study was to identify variables for selection of patients who would benefit from upfront cytoreductive nephrectomy for mRCC treated with VEGFR TKI. METHODS: Clinical data on 74 patients enrolled in 5 clinical trials conducted in Cancer Hospital (Institute), Chinese Academy of Medical Sciences from January 2006 to January 2014 were reviewed retrospectively. The survival analysis was performed by the Kaplan-Meier method. Comparisons between patient groups were performed by Chi-square test. A Cox regression model was adopted for analysis of multiple factors affecting survival, with a significance level of alpha = 0.05. RESULTS: Fifty-one patients underwent cytoreductive nephrectomy followed by targeted therapy (cytoreductive nephrectomy group) and 23 patients were treated with targeted therapy alone (noncytoreductive nephrectomy group). The median OS was 32.2 months and 23.0 months in cytoreductive nephrectomy and noncytoreductive nephrectomy groups, respectively (P = 0.041). Age <=45 years (P = 0.002), a low or high body mass index (BMI <19 or >30 kg/m2) (P = 0.008), a serum lactate dehydrogenase (LDH) concentration >1.5 * upper limit of normal (P = 0.025), a serum calcium concentration >10 mg/ml (P = 0.034), and 3 or more metastatic sites (P = 0.023) were independent preoperative risk factors for survival. The patients only with 0-2 risk factors benefited from upfront cytoreductive nephrectomy in terms of OS when compared with the patients treated with targeted therapy alone (40.0 months vs. 23.2 months, P = 0.042), while those with more than 2 risk factors did not. CONCLUSIONS: Five risk factors (age, BMI, LDH, serum calcium, and number of metastatic sites) seemed to be helpful for selecting patients who would benefit from undergoing upfront cytoreductive nephrectomy. PMID- 26904987 TI - Postoperative Low Absolute Lymphocyte Counts may Predict Poor Outcomes of Hepatocellular Carcinoma After Liver Resection. AB - BACKGROUND: The absolute lymphocyte counts (ALCs) have been reported as one of worse prognostic factors for hepatocellular carcinoma (HCC) patient after liver transplantation. The aim of this study was to assess the influence of ALCs on the outcomes of patients with hepatitis B virus (HBV)-related HCC within the Milan criteria following liver resection. METHODS: Data of patients with HCC within the Milan criteria who received liver resection between January 2007 and June 2013 were reviewed, and perioperative ALCs were carefully monitored. All potential risk factors were statistically analyzed by uni- and multi-variate analyses. The receiver operating characteristic (ROC) curve was used to determine the optimal ALCs cut-off value to predict HCC recurrence after liver resection. RESULTS: A total of 221 patients were enrolled in the current study. During the follow-up period, 106 patients experienced recurrence, and 38 patients died. Multivariate analysis suggested microvascular invasion (MVI), a tumor grade >=2, and a low postoperative ALCs in the 1st postoperative month increased the incidence of postoperative recurrence, besides, MVI, intraoperative transfusion, and a low postoperative ALCs in the 1st postoperative month were associated with poor overall survival (OS). An ROC analysis showed that a cut-off value of 1.5 * 109/L for ALCs in the 1st postoperative month predicted postoperative recurrence. The 5 year recurrence-free survival (RFS) and OS rates of patients with low postoperative ALCs were 34.5% and 64.8%, respectively, which were significantly lower than those of patients with high postoperative ALC (58.5% for RFS and 86.5% for OS). CONCLUSION: Low ALCs in the 1st postoperative month may be associated with high recurrence incidence and poor OS for patients with HBV-related HCC within the Milan criteria after liver resection. PMID- 26904988 TI - Relationship Between Clinical and Immunological Features with Magnetic Resonance Imaging Abnormalities in Female Patients with Neuropsychiatric Systemic Lupus Erythematosus. AB - BACKGROUND: Conventional magnetic resonance imaging (MRI) is the preferred neuroimaging method in the evaluation of neuropsychiatric systemic lupus erythematosus (NPSLE). The purpose of this study was to investigate the association between clinical and immunological features with MRI abnormalities in female patients with NPSLE, to screen for the value of conventional MRI in NPSLE. METHODS: A total of 59 female NPSLE patients with conventional MRI examinations were enrolled in this retrospective study. All patients were classified into different groups according to MRI abnormalities. Both clinical and immunological features were compared between MRI abnormal and normal groups. One-way analysis of variance was used to compare the systemic lupus erythematosus disease activity index (SLEDAI) score for MRI abnormalities. Multivariate logistic regression analysis investigated the correlation between immunological features, neuropsychiatric manifestations, and MRI abnormalities. RESULTS: Thirty-six NPSLE patients (61%) showed a variety of MRI abnormalities. There were statistically significant differences in SLEDAI scores (P < 0.001), incidence of neurologic disorders (P = 0.001), levels of 24-h proteinuria (P = 0.001) and immunoglobulin M (P = 0.004), and incidence of acute confusional state (P = 0.002), cerebrovascular disease (P = 0.004), and seizure disorder (P = 0.028) between MRI abnormal and normal groups. In the MRI abnormal group, SLEDAI scores for cerebral atrophy (CA), cortex involvement, and restricted diffusion (RD) were much higher than in the MRI normal group (P < 0.001, P = 0.002, P = 0.038, respectively). Statistically significant positive correlations between seizure disorder and cortex involvement (odds ratio [OR] = 14.90; 95% confidence interval [CI], 1.50 151.70; P = 0.023) and cerebrovascular disease and infratentorial involvement (OR = 10.00; 95% CI, 1.70-60.00; P = 0.012) were found. CONCLUSIONS: MRI abnormalities in NPSLE, especially CA, cortex involvement, and RD might be markers of high systemic lupus erythematosus activity. Some MRI abnormalities might correspond to neuropsychiatric manifestations and might be helpful in understanding the pathophysiology of NPSLE. PMID- 26904989 TI - Effects of Fluvastatin on Characteristics of Stellate Ganglion Neurons in a Rabbit Model of Myocardial Ischemia. AB - BACKGROUND: Stellate ganglion (SG) plays an important role in cardiovascular diseases. The electrical activity of SG neurons is involved in the regulation of the autonomic nervous system. The aim of this research was to evaluate the effects of fluvastatin on the electrophysiological characteristics of SG neurons in a rabbit model of myocardial ischemia (MI). METHODS: The MI model was induced by abdominal subcutaneous injections of isoproterenol in rabbits. Using whole cell patch clamp technique, we studied the characteristic changes of ion channels and action potentials (APs) in isolated SG neurons in control group (n = 20), MI group (n = 20) and fluvastatin pretreated group (fluvastatin group, n = 20), respectively. The protein expression of sodium channel in SG was determined by immunohistochemical analysis. RESULTS: MI and the intervention of fluvastatin did not have significantly influence on the characteristics of delayed rectifier potassium channel currents. The maximal peak current density of sodium channel currents in SG neurons along with the characteristics of activation curves, inactivation curves, and recovery curves after inactivation were changed in the MI group. The peak current densities of control group, MI group, and fluvastatin group (n = 10 in each group) were -71.77 +/- 23.22 pA/pF, -126.75 +/- 18.90 pA/pF, and -86.42 +/- 28.30 pA/pF, respectively (F = 4.862, P = 0.008). Fluvastatin can decrease the current amplitude which has been increased by MI. Moreover, fluvastatin induced the inactivation curves and post-inactive recovery curves moving to the position of the control group. But the expression of sodium channel-associated protein (Nav1.7) had no significantly statistical difference among the three groups. The percentages of Nav1.7 protein in control group, MI group, and fluvastatin group (n = 5 in each group) were 21.49 +/- 7.33%, 28.53 +/ 8.26%, and 21.64 +/- 2.78%, respectively (F = 1.495, P = 0.275). Moreover, MI reduced the electrical activity of AP and increased amplitude of AP, fluvastatin pretreatment could recover amplitude and electrical activity of AP. The probability of neurons induced continuous APs were 44.44%, 14.29%, and 28.57% in control group, MI group, and fluvastatin group, respectively. CONCLUSIONS: Fluvastatin pretreatment can recover electrophysiology characteristics of ion channel and AP in SG neurons in a rabbit model of MI. It could be considered as potential method for treating coronary heart diseases. PMID- 26904990 TI - Effects of Calcium Sulfate Combined with Platelet-rich Plasma on Restoration of Long Bone Defect in Rabbits. AB - BACKGROUND: The treatment for long bone defects has been a hot topic in the field of regenerative medicine. This study aimed to evaluate the therapeutic effects of calcium sulfate (CS) combined with platelet-rich plasma (PRP) on long bone defect restoration. METHODS: A radial bone defect model was constructed through an osteotomy using New Zealand rabbits. The rabbits were randomly divided into four groups (n = 10 in each group): a CS combined with PRP (CS-PRP) group, a CS group, a PRP group, and a positive (recombinant human bone morphogenetic protein-2) control group. PRP was prepared from autologous blood using a two-step centrifugation process. CS-PRP was obtained by mixing hemihydrate CS with PRP. Radiographs and histologic micrographs were generated. The percentage of bone regenerated bone area in each rabbit was calculated at 10 weeks. One-way analysis of variance was performed in this study. RESULTS: The radiographs and histologic micrographs showed bone restoration in the CS-PRP and positive control groups, while nonunion was observed in the CS and PRP groups. The percentages of bone regenerated bone area in the CS-PRP (84.60 +/- 2.87%) and positive control (52.21 +/- 4.53%) groups were significantly greater than those in the CS group (12.34 +/ 2.17%) and PRP group (16.52 +/- 4.22%) (P < 0.001). In addition, the bone strength of CS-PRP group (43.10 +/- 4.10%) was significantly greater than that of the CS group (20.10 +/- 3.70%) or PRP group (25.10 +/- 2.10%) (P < 0.001). CONCLUSION: CS-PRP functions as an effective treatment for long bone defects through stimulating bone regeneration and enhancing new bone strength. PMID- 26904991 TI - Renoprotective Effect of the Combination of Renin-angiotensin System Inhibitor and Calcium Channel Blocker in Patients with Hypertension and Chronic Kidney Disease. AB - BACKGROUND: Renin-angiotensin system inhibitor and calcium channel blocker (CCB) are widely used in controlling blood pressure (BP) in patients with chronic kidney disease (CKD). We carried out a meta-analysis to compare the renoprotective effect of the combination of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) and CCB (i.e., ACEI/ARB + CCB) with ACEI/ARB monotherapy in patients with hypertension and CKD. METHODS: Publications were identified from PubMed, Embase, Medline, and Cochrane databases. Only randomized controlled trials (RCTs) of BP lowering treatment for patients with hypertension and CKD were considered. The outcomes of end-stage renal disease (ESRD), cardiovascular events, BP, urinary protein measures, estimated glomerular filtration rate (GFR), and adverse events were extracted. RESULTS: Based on seven RCTs with 628 patients, ACEI/ARB + CCB did not show additional benefit for the incidence of ESRD (risk ratio [RR] = 0.84; 95% confidence interval [CI]: 0.52-1.33) and cardiovascular events (RR = 0.58; 95% CI: 0.21-1.63) significantly, compared with ACEI/ARB monotherapy. There were no significant differences in change from baseline to the end points in diastolic BP (weighted mean difference [WMD] = -1.28 mmHg; 95% CI: -3.18 to -0.62), proteinuria (standard mean difference = -0.55; 95% CI: -1.41 to -0.30), GFR (WMD = -0.32 ml/min; 95% CI: -1.53 to -0.89), and occurrence of adverse events (RR = 1.05; 95% CI: 0.72-1.53). However, ACEI/ARB + CCB showed a greater reduction in systolic BP (WMD = -4.46 mmHg; 95% CI: -6.95 to -1.97), compared with ACEI/ARB monotherapy. CONCLUSION: ACEI/ARB + CCB had no additional renoprotective benefit beyond than what could be achieved with ACEI/ARB monotherapy. PMID- 26904992 TI - Diagnostic Value of Soluble Suppression of Tumorigenicity-2 for Heart Failure. AB - BACKGROUND: Many studies have explored the diagnostic performance of soluble suppression of tumorigenicity-2 (sST2) for heart failure (HF), but the results are inconsistent. Here, we performed a meta-analysis to assess the role of sST2 in the diagnosis of HF. METHODS: We searched PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Database from inception to April 2015. Studies that investigated the diagnostic role of sST2 for HF were reviewed. The numbers of true-positive, false-positive, false negative, and true-negative results were extracted to calculate pooled diagnostic odds ratio (DOR) with 95% confidence interval (CI) and the summary receiver operating characteristic curve and area under the curve (AUC). The Spearman correlation coefficient was used to check the threshold effect. The Cochran Q statistic (P < 0.05) and the inconsistency index (I2 > 50%) were used to assess the nonthreshold effect. Meta-regression was conducted to explore the source of heterogeneity; subgroup analysis showed the results in different subgroups. Finally, the Deeks' test was performed to assess the publication bias. RESULTS: Nine articles including 10 studies were included in the meta-analysis. The pooled sensitivity was 0.84 (95% CI: 0.81-0.86), and pooled specificity was 0.74 (95% CI: 0.72-0.76). The summary DOR was 8.49 (95% CI: 4.54-15.86), and AUC was 0.81 (standard error: 0.03). The Spearman correlation coefficient identified the nonsignificant threshold effect (coefficient = 0.49, P = 0.148), but the nonthreshold effect heterogeneity was significant (Cochran Q = 58.52, P < 0.0001; I2 = 84.6%). Meta-regression found that characteristics of controls might be the suggestive source of nonthreshold effect heterogeneity (P = 0.095). Subgroup analysis found that DOR was 5.65 and 7.86, respectively for the controls of hospital patients and healthy populations. Deeks' test demonstrated that there was no publication bias (P = 0.616). CONCLUSION: The meta-analysis illustrated that sST2 might play a role in diagnosing HF. PMID- 26904993 TI - Correlation Between Brain Activation Changes and Cognitive Improvement Following Cognitive Remediation Therapy in Schizophrenia: An Activation Likelihood Estimation Meta-analysis. AB - BACKGROUND: Several studies using functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) have indicated that cognitive remediation therapy (CRT) might improve cognitive function by changing brain activations in patients with schizophrenia. However, the results were not consistent in these changed brain areas in different studies. The present activation likelihood estimation (ALE) meta-analysis was conducted to investigate whether cognitive function change was accompanied by the brain activation changes, and where the main areas most related to these changes were in schizophrenia patients after CRT. Analyses of whole-brain studies and whole-brain + region of interest (ROI) studies were compared to explore the effect of the different methodologies on the results. METHODS: A computerized systematic search was conducted to collect fMRI and PET studies on brain activation changes in schizophrenia patients from pre- to post-CRT. Nine studies using fMRI techniques were included in the meta analysis. Ginger ALE 2.3.1 was used to perform meta-analysis across these imaging studies. RESULTS: The main areas with increased brain activation were in frontal and parietal lobe, including left medial frontal gyrus, left inferior frontal gyrus, right middle frontal gyrus, right postcentral gyrus, and inferior parietal lobule in patients after CRT, yet no decreased brain activation was found. Although similar increased activation brain areas were identified in ALE with or without ROI studies, analysis including ROI studies had a higher ALE value. CONCLUSIONS: The current findings suggest that CRT might improve the cognition of schizophrenia patients by increasing activations of the frontal and parietal lobe. In addition, it might provide more evidence to confirm results by including ROI studies in ALE meta-analysis. PMID- 26904994 TI - Excision Repair Cross-complementation Group 1 is a Prognostic Biomarker in Patients with Colorectal Cancer Receiving Chemotherapy. AB - BACKGROUND: Conflicting results about the association between expression level of excision repair cross-complementation group 1 (ERCC1) and clinical outcome in patients with colorectal cancer (CRC) receiving chemotherapy have been reported. Thus, we searched the available articles and performed the meta-analysis to elucidate the prognostic role of ERCC1 expression in patients with CRC. METHODS: A thorough literature search using PubMed (Medline), Embase, Cochrane Library, Web of Science databases, and Chinese Science Citation Database was conducted to obtain the relevant studies. Pooled hazard ratios (HR s) or odds ratios (OR s) with 95% confidence intervals (CI s) were calculated to estimate the results. RESULTS: A total of 11 studies were finally enrolled in this meta-analysis. Compared with patients with lower ERCC1 expression, patients with higher ERCC1 expression tended to have unfavorable overall survival (OS) (HR = 2.325, 95% CI: 1.720-3.143, P < 0.001), progression-free survival (PFS) (HR = 1.917, 95% CI: 1.366-2.691, P < 0.001) and poor response to chemotherapy (OR = 0.491, 95% CI: 0.243-0.990, P = 0.047). Subgroup analyses by treatment setting, ethnicity, HR extraction, detection methods, survival analysis, and study design demonstrated that our results were robust. CONCLUSIONS: ERCC1 expression may be taken as an effective prognostic factor predicting the response to chemotherapy, OS, and PFS. Further studies with better study design and longer follow-up are warranted in order to gain a deeper understanding of ERCC1's prognostic value. PMID- 26904996 TI - Clinical Analysis of a Hypokalemic Salt-losing Tubulopathy Case. PMID- 26904997 TI - Laparoscopic Omohyoid Muscle Transection Surgery: A Novel Procedure Against Omohyoid Muscle Syndrome. PMID- 26904995 TI - Role of Epithelium Sodium Channel in Bone Formation. AB - OBJECTIVE: To review the recent developments in the mechanisms of epithelium sodium channels (ENaCs) induced bone formation and regulation. DATA SOURCES: Studies written in English or Chinese were searched using Medline, PubMed and the index of Chinese-language literature with time restriction from 2005 to 2014. Keywords included ENaC, bone, bone formation, osteonecrosis, estrogen, and osteoporosis. Data from published articles about the structure of ENaC, mechanism of ENaC in bone formation in recent domestic and foreign literature were selected. STUDY SELECTION: Abstract and full text of all studies were required to obtain. Studies those were not accessible and those did not focus on the keywords were excluded. RESULTS: ENaCs are tripolymer ion channels which are assembled from homologous alpha, beta, and gamma subunits. Crystal structure of ENaCs suggests that ENaC has a central ion-channel located in the central symmetry axis of the three subunits. ENaCs are protease sensitive channels whose iron-channel activity is regulated by the proteolytic reaction. Channel opening probability of ENaCs is regulated by proteinases, mechanical force, and shear stress. Several molecules are involved in regulation of ENaCs in bone formation, including nitride oxide synthases, voltage-sensitive calcium channels, and cyclooxygenase 2. CONCLUSION: The pathway of ENaC involved in shear stress has an effect on stimulating osteoblasts even bone formation by estrogen interference. PMID- 26904998 TI - Endovascular Coiling for a Ruptured Proximal Lenticulostriate Artery Aneurysm. PMID- 26904999 TI - Primary Central Nervous System Lymphoma. PMID- 26905000 TI - Agraphia in Amyotrophic Lateral Sclerosis with Frontotemporal Lobe Degeneration. PMID- 26905001 TI - A Novel Surgical Option for Urinary Tract Reconstruction in Third Renal Transplantation. PMID- 26905002 TI - Acute Hemorrhagic Cardiac Tamponade as Presenting Findings of Transmural Myocardial Infarction in an Adult Patient. PMID- 26905003 TI - Dandy-Walker Malformation and Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like Episode Syndrome: Is There a Causal or Coincidental Association? PMID- 26905004 TI - Membranous Nephropathy Associated with Tuberculosis. PMID- 26905005 TI - One-stage Hybrid Procedure for Patients with Valvular Pulmonary Stenosis and Coronary Artery Disease. PMID- 26905006 TI - Successful Treatment of Kounis Syndrome Type I Presenting as Cardiac Arrest with ST Elevation. PMID- 26905007 TI - Comparing Postoperative Pain After Laparoscopic Cholecystectomy. PMID- 26905008 TI - Study on the Postoperative Pain Calls for More Methods to Control Potential Bias. PMID- 26905009 TI - Fabrication of cm scale buckypapers of horizontally aligned multiwalled carbon nanotubes highly filled with Fe3C: the key roles of Cl and Ar-flow rates. AB - A key challenge in the fabrication of ferromagnetically filled carbon-nanotube buckypapers in the presence of Cl-radicals is the achievement of a preferential horizontal nanotube-alignment. We show that a horizontal-alignment can be achieved by tuning two main CVD parameters for a fixed dichlorobenzene concentration: the precursor-evaporation temperature and the flow rate. PMID- 26905011 TI - The impact of state of bladder fullness on tonic and phasic activation of the pelvic floor muscles in women. AB - PURPOSE: We aimed to determine if state of bladder fullness affects pelvic floor muscle activation in healthy women without urogenital symptoms. MATERIALS AND METHODS: Twenty-three nulliparous, continent female participants were recruited to participate. Women were randomized to begin the protocol with either an empty (EF) or a full (FE) bladder. Tonic and maximal voluntary pelvic floor muscle electromyographic activity were measured in three states of bladder fullness (empty, full and uncomfortably full). Electromyographic signal amplitudes were compared among bladder states using separate two-way repeated-measures analyses of variance including bladder state and test order as main effects as well as the interaction between bladder state and test order. RESULTS: Tonic activity of the pelvic floor muscles was significantly higher in the full and uncomfortably full bladder states compared to when the bladder was empty (p<0.005). Maximum voluntary electromyographic activation was unaffected by state of bladder fullness (p=0.713). CONCLUSIONS: Consistent with studies in which the bladder was filled through saline infusion, these results suggest that tonic activity of the PFMs is higher when the bladder is full compared to when it is empty. However once the bladder is moderately full, tonic PFM activity does not increase with increases in bladder volume. PMID- 26905010 TI - Smad2 and Smad3 have differential sensitivity in relaying TGFbeta signaling and inversely regulate early lineage specification. AB - The transforming growth factor beta (TGFbeta) related signaling is one of the most important signaling pathways regulating early developmental events. Smad2 and Smad3 are structurally similar and it is mostly considered that they are equally important in mediating TGFbeta signals. Here, we show that Smad3 is an insensitive TGFbeta transducer as compared with Smad2. Smad3 preferentially localizes within the nucleus and is thus sequestered from membrane signaling. The ability of Smad3 in oligomerization with Smad4 upon agonist stimulation is also impaired given its unique linker region. Smad2 mediated TGFbeta signaling plays a crucial role in epiblast development and patterning of three germ layers. However, signaling unrelated nuclear localized Smad3 is dispensable for TGFbeta signaling-mediated epiblast specification, but important for early neural development, an event blocked by TGFbeta/Smad2 signaling. Both Smad2 and Smad3 bind to the conserved Smads binding element (SBE), but they show nonoverlapped target gene binding specificity and differential transcriptional activity. We conclude that Smad2 and Smad3 possess differential sensitivities in relaying TGFbeta signaling and have distinct roles in regulating early developmental events. PMID- 26905013 TI - Synthesis, characterization, thermal properties and antiproliferative potential of copper(II) 4'-phenyl-terpyridine compounds. AB - Reactions between 4'-phenyl-terpyridine (L) and several Cu(II) salts (p toluenesulfonate, benzoate and o-, m- or p-hydroxybenzoate) led to the formation of [Cu(p-SO3C6H4CH3)L(H2O)2](p-SO3C6H4CH3) (1), [Cu(OCOPh)2L] (2), [Cu(o OCOC6H4OH)2L] (3), [Cu(m-OCOC6H4OH)2L]4.MeOH (.MeOH) and [Cu(p OCOC6H4OH)2L]5.2H2O (.2H2O), which were characterized by elemental and TG-DTA analyses, ESI-MS, IR spectroscopy and single crystal X-ray diffraction, as well as by conductivimetry. In all structures the Cu atoms present N3O3 octahedral coordination geometries, which, in 2-5, are highly distorted as a result of the chelating-bidentate mode of one of the carboxylate ligands. Intermolecular pi...pi stacking interactions could also be found in 2-5 (in the 3.569-3.651 A range and involving solely the pyridyl rings). Medium-strong hydrogen bond interactions lead to infinite 1D chains (in 1 and 4) and to an infinite 2D network (in 5). Compounds 1 and 4 show high in vitro cytotoxicity towards HCT116 colorectal carcinoma and HepG2 hepatocellular carcinoma cell lines. The antiproliferative potential of compound 1 is due to an increase of the apoptotic process that was confirmed by Hoechst staining, flow cytometry and RT-qPCR. All compounds able to non-covalently intercalate the DNA helix and induce in vitro pDNA double-strand breaks in the absence of H2O2. Concerning compound 1, the hydroxyl radical and singlet oxygen do not appear to be involved in the pDNA cleavage process and the fact that this cleavage also occurs in the absence of molecular oxygen points to a hydrolytic mechanism of cleavage. PMID- 26905012 TI - Suppression of ERK phosphorylation through oxidative stress is involved in the mechanism underlying sevoflurane-induced toxicity in the developing brain. AB - In animal models, neonatal exposure to general anesthetics significantly increased neuronal apoptosis with subsequent behavioral deficits in adulthood. Although the underlying mechanism is largely unknown, involvement of extracellular signal-regulated kinases (ERKs) is speculated since ERK phosphorylation is decreased by neonatal anesthetic exposure. Importance of ERK phosphorylation for neuronal development is underscored by our recent finding that transient suppression of ERK phosphorylation during the neonatal period significantly increased neuronal apoptosis and induced behavioral deficits. However, it is still unknown as to what extent decreased ERK phosphorylation contributes to the mechanism underlying anesthetic-induced toxicity. Here we investigated the causal relationship of decreased ERK phosphorylation and anesthetic-induced toxicity in the developing brain. At postnatal day 6 (P6), mice were exposed to sevoflurane (2%) or the blood-brain barrier-penetrating MEK inhibitor, alpha-[amino[(4-aminophenyl)thio]methylene]-2 (trifluoromethyl)benzeneacetonitrile (SL327) (50 mg/kg). Transient suppression of ERK phosphorylation by an intraperitoneal injection of SL327 at P6 significantly increased apoptosis similar to sevoflurane-induced apoptosis. Conversely, SL327 administration at P14 or P21 did not induce apoptosis, even though ERK phosphorylation was inhibited. Restoring ERK phosphorylation by administration of molecular hydrogen ameliorated sevoflurane-induced apoptosis. Together, our results strongly suggests that suppressed ERK phosphorylation is critically involved in the mechanism underlying anesthetic-induced toxicity in the developing brain. PMID- 26905014 TI - Quantum Symmetry Breaking of Exciton/Polaritons in a Metal-Nanorod Plasmonic Array. AB - We study the collective, superradiant behavior in the system of emitter-dressed Ag nanorods. Starting from the Drude model for the plasmon oscillations, we arrive at a semiempirical Hamiltonian describing the coupling between quantized surface plasmon modes and the quantum emitters that can be controlled by manipulating their geometry, spacing, and orientation. Further, identifying the lowest polariton mode as SP-states dressed by excitons in the vicinity of k = 0, we examine conditions allowing for the polariton quantum-phase transition. Though the system is formally a 1D array, we show that the polariton states of interest can undergo a quantum-phase transition to form a Bose condensate at finite temperatures for physically accessible parameter ranges. PMID- 26905015 TI - Satisfaction with Life Scale (SLS-6): First validation study in Parkinson's disease population. AB - INTRODUCTION: To explore the psychometric attributes of a new Satisfaction with Life Scale (SLS-6) in a wide Spanish-speaking population with Parkinson's disease (PD). METHODS: This was an international, cross-sectional study. Several rater based and patient-reported outcomes measures for evaluation of PD (e.g., Scales for Outcomes in Parkinson's Disease-Motor) and other constructs (e.g., Duke-UNC Functional Social Support Questionnaire, Scale for Living with Chronic Illness) were applied together with the SLS-6. Acceptability, scaling assumptions, reliability, precision, and construct validity were tested. RESULTS: The study included 324 patients from five countries, with age (mean +/- standard deviation) 66.67 +/- 10.68 years. None of the SLS-6 items had missing values and all acceptability parameters fulfilled the standard criteria. Scaling assumptions allowed the calculation of a summary index from items 2 to 6, complementary to the global evaluation (item 1). For these five items, Cronbach's alpha was 0.85; the corrected item-total correlation 0.53-0.73; inter-item correlation, 0.45 0.70, with an item homogeneity index of 0.55. The standard error of measurement, based on Cronbach's alpha for a single observation, was 3.48. SLS-6 correlations were moderate to strong (rs >= 0.35) with the patient-reported outcomes and weak to moderate with the rater-based assessments used in the study. The SLS-6 total score was significantly different according to PD severity levels established according to Hoehn and Yahr staging, Clinical Impression of Severity Index, and Patient-Based Global Impression of Severity scale. CONCLUSION: The results suggest that SLS-6 is an easy, feasible, acceptable, consistent, precise and valid measure to evaluate satisfaction with life in PD patients. PMID- 26905016 TI - Direct Endoscopic Visualization Combined with Ultrasound Guided Access during Percutaneous Nephrolithotomy: A Feasibility Study and Comparison to a Conventional Cohort. AB - PURPOSE: Percutaneous nephrolithotomy access may be technically challenging and result in significant radiation exposure. In an attempt to reduce percutaneous nephrolithotomy radiation exposure, a novel technique combining ultrasound and direct ureteroscopic visualization was developed and reviewed. MATERIALS AND METHODS: Ureteroscopy without fluoroscopy was used to determine the optimal calyx for access, which was punctured with a Chiba needle under percutaneous ultrasound guidance. Next a wire was passed into the collecting system and ureteroscopically pulled into the ureter using a basket. Tract dilation and sheath and nephrostomy tube placement were performed under direct ureteroscopic visualization. Twenty consecutive patients undergoing this novel technique were reviewed and compared to 20 matched patients treated with conventional percutaneous nephrolithotomy. Mann-Whitney U and Pearson chi-square tests were used for comparisons with p <0.05 considered significant. RESULTS: Using this novel technique mean fluoroscopy access time was 3.5 seconds (range 0 to 27.9) and mean total fluoroscopic time was 8.8 seconds (range 0 to 47.1). Mean operative time was 232 minutes (range 87 to 533), estimated blood loss was 111 ml, the stone-free rate was 65% and the complication rate was 25%. Compared to 20 matched conventional percutaneous nephrolithotomy cases, there was no difference in operative time (p=0.76), estimated blood loss (p=0.64), stone-free rate (p=0.50) or complications (p=1.00). However, the novel technique resulted in a significant reduction in fluoroscopy access time (3.5 vs 915.5 seconds, p <0.001) and total fluoroscopy time (8.8 vs 1,028.7 seconds, p <0.001). CONCLUSIONS: This study demonstrates the feasibility of combined ultrasound and ureteroscopic assisted access for percutaneous nephrolithotomy. A greater than 99% reduction in fluoroscopy time was achieved using this technique. PMID- 26905017 TI - Lower Urinary Tract Symptoms and Risk of Nonspine Fractures among Older Community Dwelling U.S. Men. AB - PURPOSE: Among older men, moderate and severe lower urinary tract symptoms are associated with increased fall risk compared to mild lower urinary tract symptoms. Falls are a major risk factor for fractures. Therefore, we assessed associations of lower urinary tract symptoms with fracture risk in community dwelling U.S. men age 65 years or older. MATERIALS AND METHODS: We conducted a prospective study in the MrOS (Osteoporotic Fractures in Men Study) cohort. Men were enrolled at 6 U.S. sites. The AUA-SI, lower urinary tract symptoms medication use, fracture risk factors and potential confounders were recorded at baseline and every 2 years thereafter for 4 assessments. Lower urinary tract symptom severity was categorized from the AUA-SI as mild (0 to 7 points), moderate (8 to 19 points) or severe (20 or more points). Associations of lower urinary tract symptom severity with fracture rate were estimated with HRs and 95% CIs from extended proportional hazards regression. RESULTS: Among 5,989 men with baseline AUA-SI score and hip bone mineral density measures, 745 incident nonspine fractures occurred during 43,807 person-years of followup. In a multivariable model adjusted for age, enrollment site, baseline hip bone mineral density, falls in the last year and prevalent fracture before baseline, there were no significant associations of moderate (HR 0.9, 95% CI 0.8-1.1) or severe (HR 1.0, 95% CI 0.8-1.3) lower urinary tract symptoms with fracture risk. None of the individual lower urinary tract symptoms assessed on the AUA-SI, including nocturia and urgency, was associated with increased fracture risk. CONCLUSIONS: In this cohort of older U.S. men, lower urinary tract symptoms were not independently associated with fracture risk. PMID- 26905018 TI - Erectile Function Recovery after Radical Prostatectomy in Men with High Risk Features. AB - PURPOSE: We describe the efficacy of radical prostatectomy to achieve complete primary tumor excision while preserving erectile function in a cohort of patients with high risk features in whom surgical resection was tailored according to clinical staging, biopsy data, preoperative imaging and intraoperative findings. MATERIALS AND METHODS: In a retrospective review we identified 584 patients with high risk features (prostate specific antigen 20 ng/ml or greater, clinical stage T3 or greater, preoperative Gleason grade 8-10) who underwent radical prostatectomy between 2006 and 2012. The probability of neurovascular bundle preservation was estimated based on preoperative characteristics. Positive surgical margin rates and erectile function recovery were determined in patients who had some degree of neurovascular bundle preservation. RESULTS: The neurovascular bundles were resected bilaterally in 69 (12%) and unilaterally in 91 (16%) patients. The remaining patients had some degree of bilateral neurovascular bundle preservation. Preoperative features associated with a lower probability of neurovascular bundle preservation were primary biopsy Gleason grade 5 and clinical stage T3 disease. Among the patients with some degree of neurovascular bundle preservation 125 of 515 (24%) had a positive surgical margin, and 75 of 160 (47%) men with preoperatively functional erections and available erectile function followup had recovered erectile function within 2 years. CONCLUSIONS: High risk features should not be considered an indication for complete bilateral neurovascular bundle resection. Some degree of neurovascular bundle preservation can be done safely by high volume surgeons in the majority of these patients with an acceptable rate of positive surgical margins. Nearly half of high risk patients with functional erections preoperatively recover erectile function after radical prostatectomy. PMID- 26905019 TI - Urine Trouble: Alterations in Brain Function Associated with Bladder Pain. AB - PURPOSE: Chronic bladder pain is a debilitating condition often accompanied by alterations in affective and autonomic function. Many symptoms associated with chronic bladder pain are mediated by the central nervous system. In this review data from preclinical animal models and human neuroimaging studies were analyzed and a theoretical supraspinal bladder pain network was generated. MATERIALS AND METHODS: We comprehensively reviewed the literature using PubMed(r) and Google ScholarTM. Relevant reviews and original research articles, and the cited references were summarized and then organized on a neuroanatomical basis. RESULTS: The brain loci the most predominant in the bladder pain literature are the thalamus, parabrachial nucleus, cerebral cortex, amygdala, hypothalamus, periaqueductal gray and rostral ventromedial medulla. This review highlights each of these regions, discussing the molecular and physiological changes that occur in each in the context of bladder pain. CONCLUSIONS: A complex network of brain loci is involved in bladder pain modulation. Studying these brain regions and the changes that they undergo during the transition from acute to chronic bladder pain will provide novel therapeutic strategies for patients with chronic bladder pain diseases such as interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome. PMID- 26905020 TI - Comparing Zero Ischemia Laparoscopic Radio Frequency Ablation Assisted Tumor Enucleation and Laparoscopic Partial Nephrectomy for Clinical T1a Renal Tumor: A Randomized Clinical Trial. AB - PURPOSE: We evaluated the functional outcome, safety and efficacy of zero ischemia laparoscopic radio frequency ablation assisted tumor enucleation compared with conventional laparoscopic partial nephrectomy. MATERIALS AND METHODS: A prospective randomized controlled trial was conducted from April 2013 to March 2015 in patients with cT1a renal tumor scheduled for laparoscopic nephron sparing surgery. All patients were followed for at least 12 months. Patients in the laparoscopic radio frequency ablation assisted tumor enucleation group underwent tumor enucleation after radio frequency ablation without hilar clamping. The primary outcome was the change in glomerular filtration rate of the affected kidney by renal scintigraphy at 12 months. Secondary outcomes included changes in estimated glomerular filtration rate, estimated blood loss, operative time, hospital stay, postoperative complications and oncologic outcomes. The Pearson chi-square or Fisher exact, Student t-test and Wilcoxon rank sum tests were used. RESULTS: The trial ultimately enrolled 89 patients, of whom 44 were randomized to the laparoscopic radio frequency ablation assisted tumor enucleation group and 45 to the laparoscopic partial nephrectomy group. In the laparoscopic partial nephrectomy group 1 case was converted to radical nephrectomy. Compared with the laparoscopic partial nephrectomy group, patients in the laparoscopic radio frequency ablation assisted tumor enucleation group had a smaller decrease in glomerular filtration rate of the affected kidney at 3 months (10.2% vs 20.5%, p=0.001) and 12 months (7.6% vs 16.2%, p=0.002). Patients in the laparoscopic radio frequency ablation assisted tumor enucleation group had a shorter operative time (p=0.002), lower estimated blood loss (p <0.001) and a shorter hospital stay (p=0.029) but similar postoperative complications (p=1.000). There were no positive margins or local recurrence in this study. CONCLUSIONS: Zero ischemia laparoscopic radio frequency ablation assisted tumor enucleation enables tumor excision with better renal function preservation compared to conventional laparoscopic partial nephrectomy. Less blood loss and a shorter operative time were achieved with similar postoperative complication rates. PMID- 26905021 TI - Gamma emitters in atmospheric precipitation in Krakow (Southern Poland) during the years 2005-2015. AB - The results of the sum of dry and wet activity deposition for naturally occurring 7Be, 210Pb, 40K, 22Na and anthropogenic 137Cs radionuclides in Krakow (Southern Poland) for the samples collected over 10 years (from August 2005 to July 2015) are presented and discussed. The radionuclides were determined using low background gamma spectrometry with HPGe detectors. Additionally, in this paper there are shown the results of activity concentrations in water from air precipitation for 7Be, 210Pb, 22Na, 40K and 137Cs radioisotopes from the period of 7 years (from August 2008 to July 2015). For all these series the statistical analysis including Spearman correlations, effects of seasonal variation and multiple regression models were conducted. After excluding two months from 2011 affected by the Fukushima accident, high Spearman correlation factors (R > 0.5) for activity deposition were noticed for the pair of the cosmogenic radionuclides 7Be and 22Na (R = 0.508) and between 210Pb and 7Be (R = 0.570). High correlation was noted between activity deposition and amount of precipitation for 7Be (R = 0.677). The seasonal correlations between 7Be-22Na, 40K-137Cs, 210Pb-137Cs and 7Be-210Pb were investigated and the highest correlation coefficient R = 0.731 for the 40K-137Cs pair was in the spring season. High correlations were observed also between 210Pb and 7Be for autumn (R = 0.594), 40K-137Cs in summer (R = 0.582), 7Be-22Na in spring (R = 0.635) and 210Pb-137Cs in autumn (R = 0.672). The multiple regression approach showed the interesting difference in scavenging mechanisms of cosmogenic and terrestrial radionuclides. According to that model, the deposition of cosmogenic nuclides was noticeably related to the amount of precipitation, while the deposition of terrestrial radionuclides did not show such dependence. PMID- 26905022 TI - Steric and Electronic Influence of Aryl Isocyanides on the Properties of Iridium(III) Cyclometalates. AB - Cyclometalated iridium complexes with efficient phosphorescence and good electrochemical stability are important candidates for optoelectronic devices. Isocyanide ligands are strong-field ligands: when attached to transition metals, they impart larger HOMO-LUMO energy gaps, engender higher oxidative stability at the metal center, and support rugged organometallic complexes. Aryl isocyanides offer more versatile steric and electronic control by selective substitution at the aryl ring periphery. Despite a few reports of alkyl isocyanide of cyclometalated iridium(III), detailed studies on analogous aryl isocyanide complexes are scant. We report the synthesis, photophysical properties, and electrochemical properties of 11 new luminescent cationic biscyclometalated bis(aryl isocyanide)iridium(III) complexes. Three different aryl isocyanides--2,6 dimethylphenyl isocyanide (CNAr(dmp)), 2,6-diisopropylphenyl isocyanide (CNAr(dipp)), and 2-naphthyl isocyanide (CNAr(nap))--were combined with four cyclometalating ligands with differential pi-pi* energies--2-phenylpyridine (ppy), 2,4-difluorophenylpyridine (F2ppy), 2-benzothienylpyridine (btp), and 2 phenylbenzothiazole (bt). Five of them were crystallographically characterized. All new complexes show wide redox windows, with reduction potentials falling in a narrow range of -2.02 to -2.37 V and oxidation potentials spanning a wider range of 0.97-1.48 V. Efficient structured emission spans from the blue region for [(F2ppy)2Ir(CNAr)2]PF6 to the orange region for [(btp)2Ir(CNAr)2]PF6, demonstrating that isocyanide ligands can support redox-stable luminescent complexes with a range of emission colors. Emission quantum yields were generally high, reaching a maximum of 0.37 for two complexes, whereas btp-ligated complexes had quantum yields below 1%. The structure of the CNAr ligand has a minimal effect on the photophysical properties, which are shown to arise from ligand centered excited states with very little contribution from metal-to-ligand charge transfer in most cases. PMID- 26905023 TI - News and Views--April 2016. PMID- 26905024 TI - An orbital hydatid cyst involving inferior rectus muscle: A case report. AB - The orbital hydatid cyst is a rare entity and although most of them are located in superolateral and superomedial angles of orbits, involvement of inferior sites is uncommon. We report a 12-year-old case of primary hydatid cyst situated in inferior rectus muscle which was undergone surgical removal. Magnetic resonance imaging (MRI) was used for differential diagnosis of hydatid cyst. Moreover, histological analysis was performed, after the cyst removal, to confirm the diagnosis. Early clinical and radiological evaluations and subsequent surgical excision is the mainstay of treatment and should be performed to prevent severe complications caused by the advanced and ruptured cysts. PMID- 26905025 TI - Moxifloxacin and gatifloxacin for initial therapy of tuberculosis: a meta analysis of randomized clinical trials. AB - Moxifloxacin (MOX) and gatifloxacin (GAT) have exhibited promising mycobactericidal activity, and a number of clinical trials have been conducted in recent decades to compare the treatment efficacy of MOX-containing and/or GAT containing regimens with the standard regimen. The aim of this meta-analysis for clinical trials of MOX- or GAT-containing regimens was to evaluate their treatment efficacy and safety in initial therapy for drug-sensitive tuberculosis (TB). Databases were searched for randomized controlled trials, and nine studies with 6980 patients were included. We found that fluoroquinolone substitution for isoniazid or ethambutol in short-course regimens might result in more frequent unfavorable treatment outcomes compared with the standard regimen-in particular, an increased incidence of relapse. In a per-protocol analysis, MOX-containing regimens had slightly higher rates of sputum culture conversion at two months than the standard regimen (RR 1.08, 95% CI 1.04-1.11, P <0.001); there was no significant difference in the rate of sputum conversion between the GAT containing regimens and the standard regimen (RR 1.13, 95% CI 0.96-1.33, P = 0.13). There were no significant differences in the incidence of death from any cause, including TB, nor were there serious adverse events between the MOX- or GAT-containing regimens and the standard regimen. In conclusion, MOX or GAT might not have the ability to shorten treatment duration in the initial therapy for tuberculosis despite the non-inferiority or even slightly better efficacy in the early phase of treatment compared with the standard regimen. Furthermore, it is safe to include MOX or GAT in initial TB treatment. PMID- 26905027 TI - Aedes mosquitoes and Zika virus infection: an A to Z of emergence? PMID- 26905026 TI - Genetic features of Mycobacterium tuberculosis modern Beijing sublineage. AB - Mycobacterium tuberculosis (MTB) Beijing strains have caused a great concern because of their rapid emergence and increasing prevalence in worldwide regions. Great efforts have been made to investigate the pathogenic characteristics of Beijing strains such as hypervirulence, drug resistance and favoring transmission. Phylogenetically, MTB Beijing family was divided into modern and ancient sublineages. Modern Beijing strains displayed enhanced virulence and higher prevalence when compared with ancient Beijing strains, but the genetic basis for this difference remains unclear. In this study, by analyzing previously published sequencing data of 1082 MTB Beijing isolates, we determined the genetic changes that were commonly present in modern Beijing strains but absent in ancient Beijing strains. These changes include 44 single-nucleotide polymorphisms (SNPs) and two short genomic deletions. Through bioinformatics analysis, we demonstrated that these genetic changes had high probability of functional effects. For example, 4 genes were frameshifted due to premature stop mutation or genomic deletions, 19 nonsynonymous SNPs located in conservative codons, and there is a significant enrichment in regulatory network for all nonsynonymous mutations. Besides, three SNPs located in promoter regions were verified to alter downstream gene expressions. Our study precisely defined the genetic features of modern Beijing strains and provided interesting clues for future researches to elucidate the mechanisms that underlie this sublineage's successful expansion. These findings from the analysis of the modern Beijing sublineage could provide us a model to understand the dynamics of pathogenicity of MTB. PMID- 26905029 TI - Density of States for Warped Energy Bands. AB - Warping of energy bands can affect the density of states (DOS) in ways that can be large or subtle. Despite their potential for significant practical impacts on materials properties, these effects have not been rigorously demonstrated previously. Here we rectify this using an angular effective mass formalism that we have developed. To clarify the often confusing terminology in this field, "band warping" is precisely defined as pertaining to any multivariate energy function E(k) that does not admit a second-order differential at an isolated critical point in k-space, which we clearly distinguish from band non parabolicity. We further describe band "corrugation" as a qualitative form of band warping that increasingly deviates from being twice differentiable at an isolated critical point. These features affect the density-of-states and other parameters ascribed to band warping in various ways. We demonstrate these effects, providing explicit calculations of DOS and their effective masses for warped energy dispersions originally derived by Kittel and others. Other physical and mathematical examples are provided to demonstrate fundamental distinctions that must be drawn between DOS contributions that originate from band warping and contributions that derive from band non-parabolicity. For some non-degenerate bands in thermoelectric materials, this may have profound consequences of practical interest. PMID- 26905030 TI - Control Cross-sectional Study Evaluating an Antibiotic Prevention Strategy in 30 Pregnancies Under Clean Intermittent Self-catheterization and Review of Literature. AB - OBJECTIVE: To assess the efficacy and safety of a weekly oral cycling antibiotic (WOCA) strategy to prevent UTI in women. MATERIALS AND METHODS: We performed a monocentric, comparative, retrospective, cross-sectional study on pregnant women under clean intermittent self catheterization between January 2008 and December 2014. WOCA consisted the administration of a single-dose antibiotic, alternating antibiotic A and B once every 2 weeks, according to previous urine cultures. RESULTS: Twenty-five women carried out 30 pregnancies. Thirteen pregnancies (43.3%) were in the WOCA group (WCG) strategy and 17 were in the non-WOCA group (NWCG) (56.7%). In the 19 (63.3%) pregnancies with urinary tract infection (UTI), 5 (38.4%) were in WCG, 14 (82.3%) were not (P = .023). There were more cystitis in NWCG (76.5% vs 23.1% P = .009) but more colonization in WCG (46.2% vs 5.8% P = .025). UTIs were due to Escherichia coli, Enterobacter cloacae, and Klebsiella pneumoniae. There was a nonsignificant increase in preterm birth in NWCG (35.3% vs 7.7% P = .10), no small for gestational age neonates, and no significant difference for the mode of delivery, birthweight, and neonatal outcome. CONCLUSION: According to our result, WOCA seems safe and effective on symptomatic UTI frequency and could be promoted to help physicians to manage specific risks in pregnancy. PMID- 26905031 TI - Ves.Pa.-Designing a Novel Robotic Intracorporeal Orthotopic Ileal Neobladder. AB - OBJECTIVE: To present a detailed description of the "Ves.Pa." procedure to create a novel robotic intracorporeal ileal orthotopic neobladder, together with technical tips for the creation of a time-efficient robotic intracorporeal neobladder. MATERIALS AND METHODS: We evaluated the presumed volume of the final Ves.Pa. in silico, exploring ex vivo the anatomical and technical feasibility of reconfiguring the bowel. During tests performed in a robotic pelvic model, procedures were recorded to identify possible improvements in operating times. RESULTS: After initial evaluation of the anatomical feasibility of the technique, its practicability was confirmed during ex vivo tests. It is also possible to create two different versions of the pouch, in cases of short right or short left ureter ("Ves.Pa. Reverse"). Tests on our robotic pelvic model confirmed the feasibility of the technique, and some details to improve its time efficiency were identified, for example, further simplification of the suturing of the neobladder. CONCLUSION: Despite the increasing use of robotic radical cystectomy, most urological departments do not perform "ideal" intracorporeal urinary diversion due to perceived technical difficulties in reconfiguring the ileum and operating times in comparison with open surgery. An idea for a novel intracorporeal robotic orthotopic neobladder (with many characteristics for creating a feasible test pouch) has been designed. Clinical studies are needed to confirm these findings. PMID- 26905032 TI - Practical Guidance on the Role of Corticosteroids in the Treatment of Metastatic Castration-resistant Prostate Cancer. AB - Corticosteroids have been used in combination with chemotherapy for the treatment of metastatic castration-resistant prostate cancer (mCRPC) for more than three decades, particularly to treat pain, inflammation, and edema. More recently, they have been used in combination with hormonal agents. The importance of corticosteroids in mCRPC is due to their ability to manage adverse effects, reduce symptoms, and improve patients' quality of life. The appropriate selection of available options in mCRPC should be based on careful consideration of a patient's profile and comorbidities. This review provides an overview of the role of corticosteroids in treating mCRPC for the practicing urologist. PMID- 26905033 TI - Overexpression of Insulin-like Growth Factor-1 Receptor Is Associated With Penile Cancer Progression. AB - OBJECTIVE: To evaluate insulin-like growth factor-1 receptor (IGF1R) expression in penile cancer and its association with oncologic outcomes. METHODS: Tissue microarrays were constructed from 53 patients treated at our institution. Expression of IGF1R was evaluated using a Her2-like scoring system. Overexpression was defined as 1+ or greater membranous staining. Association of IGF1R expression with pathologic features was assessed with comparative statistics, and association with local recurrence, progression to nodal or distance metastases, or death was assessed with Kaplan-Meier survival analysis and Cox proportional hazard regression models. RESULTS: Overall, IGF1R overexpression was seen in 33 (62%) cases. With a median follow-up of 27.8 months, IGF1R overexpression was associated with inferior progression-free survival (PFS) (P = .003). In a multivariable model controlling for grade, T stage, perineural invasion, and lymphovascular invasion, IGF1R expression was independently associated with disease progression (hazard ratio 2.3, 95% confidence interval 1.1-5.1, P = .03. Comparing patients without IGF1R overexpression to those with overexpression, 5-year PFS was 94.1% vs 45.8%. CONCLUSION: IGF1R overexpression was associated with inferior PFS in penile cancer. Drugs that target IGF1R and downstream messengers may have a therapeutic benefit in patients that exhibit IGF1R overexpression. PMID- 26905035 TI - Correction: Spectroscopic characteristics of the OSIRIS near-backscattering crystal analyser spectrometer on the ISIS pulsed neutron source. AB - Correction for 'Spectroscopic characteristics of the OSIRIS near-backscattering crystal analyser spectrometer on the ISIS pulsed neutron source' by Mark T. F. Telling et al., Phys. Chem. Chem. Phys., 2005, 7, 1255-1261. PMID- 26905036 TI - The essential role of inorganic substrate in the migration and osteoblastic differentiation of mesenchymal stem cells. AB - The physical environment, which is an integral part of the stem cell niche, is critical in regulating stem cell functions and differentiation into specific lineages. Previous studies have primarily focused on modulating the polymeric matrixes, including the extracellular matrix. Here, we report that the presence of the inorganic substrate (Ti and hydroxyapatite (HA)) in addition to the collagen overlayer plays an essential role in cytoskeletal organization, migration and differentiation of mesenchymal stem cells (MSCs). The osteogenic differentiation of MSCs was suppressed on pure collagen substrate alone, despite collagen greatly enhancing the MSC adhesion and proliferation. The results indicated a strong correlation between MSC motility and osteoblastic differentiation. In particular, the presence of the inorganic matrix promoted the activation of the canonical WNT-beta-Catenin pathway and stimulated transcription, leading to osteoblastic differentiation, which was likely due to the internal forces generated "dynamically" during cell migration. Compared to the Ti substrate, hydroxyapatite promoted the collagen self-assembly and the formation of the collagen fibrous network, which is critical for MSC motility and osteogenic differentiation. The HA-collagen matrix exhibited the most favourable stress fibre formation, the longest migration distance (2.8-fold higher than that of the pure collagen sample and 1.9-fold higher than that of Ti-collagen), and the best osteogenic differentiation activities. These findings might have important implications for our understanding of the fundamental MSC functions and the optimal design of bone regeneration materials. PMID- 26905034 TI - Community referral for presumptive TB in Nigeria: a comparison of four models of active case finding. AB - BACKGROUND: Engagement of communities and civil society organizations is a critical part of the Post-2015 End TB Strategy. Since 2007, many models of community referral have been implemented to boost TB case detection in Nigeria. Yet clear insights into the comparative TB yield from particular approaches have been limited. METHODS: We compared four models of active case finding in three Nigerian states. Data on presumptive TB case referral by community workers (CWs), TB diagnoses among referred clients, active case finding model characteristics, and CWs compensation details for 2012 were obtained from implementers and CWs via interviews and log book review. Self-reported performance data were triangulated against routine surveillance data to assess concordance. Analysis focused on assessing the predictors of presumptive TB referral. RESULTS: CWs referred 4-22% of presumptive TB clients tested, and 4-24% of the total TB cases detected. The annual median referral per CW ranged widely among the models from 1 to 48 clients, with an overall average of 13.4 referrals per CW. The highest median referrals (48 per CW/yr) and mean TB diagnoses (7.1/yr) per CW (H =70.850, p < 0.001) was obtained by the model with training supervision, and $80/quarterly payments (Comprehensive Quotas-Oriented model). The model with irregularly supervised, trained, and compensated CWs contributed the least to TB case detection with a median of 13 referrals per CW/yr and mean of 0.53 TB diagnoses per CW/yr. Hours spent weekly on presumptive TB referral made the strongest unique contribution (Beta = 0.514, p < 0.001) to explaining presumptive TB referral after controlling for other variables. CONCLUSION: All community based TB case-finding projects studied referred a relative low number of symptomatic individuals. The study shows that incentivized referral, appropriate selection of CWs, supportive supervision, leveraged treatment support roles, and a responsive TB program to receive clients for testing were the key drivers of community TB case finding. PMID- 26905037 TI - Biomechanical and morphological study of a new elastic mesh (Ciberlastic) to repair abdominal wall defects. AB - The aim of this study was to conduct a preclinical evaluation of the behaviour of a new type of abdominal LW prosthesis (Ciberlastic), which was designed with a non-absorbable elastic polyurethane monofilament (Assuplus, Assut Europe, Italy) to allow greater adaptability to mechanical area requirements and higher bio mimicking with the newly formed surrounding tissues. Our hypothesis was that an increase in the elasticity of the mesh filament could improve the benefits of LW prostheses. To verify our hypothesis, we compared the short- and long-term behaviour of Ciberlastic and Optilene((r)) elastic commercial meshes by repairing the partially herniated abdomen in New Zealand White rabbits. The implanted meshes were mechanically and histologically assessed at 14 and 180 days post implant. We mechanically characterized the partially herniated repaired muscle tissue and also determined mesh shrinkage at different post-implant times. This was followed by a histological study in which the tissue incorporation process was analysed over time. The new prosthesis designed by our group achieved good behaviour that was similar to that of Optilene((r)), one of the most popular LW prostheses on the market, with the added advantage of its elastic property. The mechanical properties are significantly lower than those of the polypropylene Optilene((r)) mesh, and the new elastic mesh meets the basic mechanical requirements for positioning in the abdominal wall, which was also demonstrated by the absence of recurrences after implantation in the experimental model. We found that the growth of a connective tissue rich in collagen over the hernial defect and the proper deposit of the collagen fibres in the regenerated tissue substantially modified the original properties of the mesh, thereby increasing its biomechanical strength and making the whole tissue/mesh stiffer. PMID- 26905039 TI - Reflections on antibiotic resistance and what to do about it. PMID- 26905038 TI - The relations of age and pubertal development with cortisol and daily stress in youth at clinical risk for psychosis. AB - BACKGROUND: Prodromal syndromes often begin in adolescence - a period of neurodevelopmental changes and heightened stress sensitivity. Research has shown elevated stress and cortisol in individuals at clinical high risk (CHR) for psychosis. This cross-sectional study examined relations of age and pubertal status with cortisol and self-reported stress in healthy controls (HCs) and CHR adolescents. It was hypothesized that the relations of age and pubertal stage with cortisol and stress would be more pronounced in CHR youth. METHODS: Participants were 93 HCs and 348 CHR adolescents from the North American Prodrome Longitudinal Study (NAPLS). At baseline, measures of stress (Daily Stress Inventory - DSI), Tanner stage (TS), and salivary cortisol were obtained. RESULTS: ANCOVA revealed increased DSI scores with age for both groups, and higher DSI scores in CHR adolescents than HCs, with a more pronounced difference for females. Contrary to prediction, with age controlled, HCs showed greater TS related DSI increases. Analysis of cortisol showed no significant interactions, but a main effect of age and a trend toward higher cortisol in the CHR group. Correlations of cortisol with TS were higher in HC than CHR group. CONCLUSIONS: Stress measures increased with age in HC and CHR adolescents, and DSI scores also increased with TS in HCs. The results do not support a more pronounced age or TS increase in stress measures in CHR adolescents, but instead suggest that stress indices tend to be elevated earlier in adolescence in the CHR group. Potential determinants of findings and future directions are discussed. PMID- 26905041 TI - A series of dinuclear Dy(iii) complexes bridged by 2-methyl-8-hydroxylquinoline: replacement on the periphery coordinated beta-diketonate terminal leads to different single-molecule magnetic properties. AB - A series of HMq-bridged dinuclear dysprosium complexes, namely, [Dy(acac)2(CH3OH)]2(MU-HMq)2 (1), [Dy(DBM)2]2(MU-HMq)2(n-C6H14) (2), [Dy(hmac)2]2(MU-HMq)2 (3) and [Dy(hfac)3]2(MU-HMq)2 (4) (HMq = 2-methyl-8 hydroxyquinoline, acac = acetylacetone, DBM = dibenzoylmethane, hmac = hexamethylacetylacetonate and hfac = hexafluoroacetylacetonate), were structurally and magnetically characterized. X-ray crystallographic analyses of the structures reveal that HMq serves as the effective bridge to link two Dy(III) centers by means of the phenoxyl oxygen and nitrogen atoms and the periphery beta diketonate ligands complete the coordination sphere by bidentate oxygen atoms. The different substituents on the beta-diketonate terminal lead to different coordination models mostly due to the steric hindrance of these substituents, and the electron-withdrawing or donating effects likely influence the strength of the ligand fields and the Dy(III) ion anisotropy. Measurements of alternating-current (ac) susceptibility on complexes 1-4 reveal that complexes 3 and 4 display significant zero-field single-molecule magnetic (SMM) behavior with barrier energy Ueff/kB = 14.8 K, tau0 = 1.8 * 10(-5) s and Ueff/kB = 9.2 K, tau0 = 1.7 * 10(-5) s, respectively, whereas 1 and 2 exhibit field-induced SMM behavior, and these differences are attributed to the alteration on the periphery beta diketonate ligands. Their distinct slow magnetic relaxation behaviors were related to their different individual Dy(III) ion magnetic anisotropy and intramolecular coupling, which were confirmed by ab initio calculations. PMID- 26905040 TI - Trimeric PEG-Conjugated Exendin-4 for the Treatment of Sepsis. AB - Exendin-4 (EX4), a glucagon-like peptide-1 receptor (GLP-1R) agonist that regulates blood glucose levels, has been used in the management of type-2 diabetes mellitus. EX4 can be PEGylated to improve its antidiabetic effects by enhancing its stability and extending the circulation half-life. Here, to determine whether PEGylated EX4 is effective for the treatment of sepsis, C terminal thiol-specific PEGylated EX4s with linear maleimide-PEG-2K, -5K, -20K and trimeric maleimide-PEG-50K (hereafter referred to as EX4-2K, EX4-5K, EX4-20K, and EX4-50K, respectively) were prepared, and their antiseptic responses were investigated. These PEGylated EX4s reduced cecal ligation and puncture (CLP) induced organ injury by decreasing hyperpermeability, and suppressing interactions between leukocytes and endothelial cells. The binding avidity and stability of EX4-50K toward GLP-1R were superior to that of wild-type EX4, as was the circulation half-life of EX4-50K. In addition, the antiseptic effects of EX4 50K were superior to those of other PEGylated EX4s, which may be attributed to enhanced proteolytic stability, longer circulation half-life, and higher receptor binding affinity of EX4-50K due to its trimeric PEG structure. Therefore, EX4-50K may decrease CLP-induced septic mortality in vivo. There are currently neither effective preventatives against nor treatment options for sepsis; our results show that EX4-50K has the potential to treat sepsis. PMID- 26905042 TI - Enzymatically activated emulsions stabilised by interfacial nanofibre networks. AB - We report on-demand formation of emulsions stabilised by interfacial nanoscale networks. These are formed through biocatalytic dephosphorylation and self assembly of Fmoc(9-fluorenylmethoxycarbonyl)dipeptide amphiphiles in aqueous/organic mixtures. This is achieved by using alkaline phosphatase which transforms surfactant-like phosphorylated precursors into self-assembling aromatic peptide amphiphiles (Fmoc-tyrosine-leucine, Fmoc-YL) that form nanofibrous networks. In biphasic organic/aqueous systems, these networks form preferentially at the interface thus providing a means of emulsion stabilisation. We demonstrate on-demand emulsification by enzyme addition, even after storage of the biphasic mixture for several weeks. Experimental (Fluorescence, FTIR spectroscopy, fluorescence microscopy, electron microscopy, atomic force microscopy) and computational techniques (atomistic molecular dynamics) are used to characterise the interfacial self-assembly process. PMID- 26905043 TI - Iowa Gambling Task Performance in Elderly Persons with a Lifetime History of Suicidal Acts. AB - OBJECTIVES: Suicide in the elderly is a major public health problem. In the present study, we aimed to further understand the mechanisms of suicidal vulnerability in the elderly, focusing on high-risk decision-making. This trait like impairment has been extensively studied in adolescent and middle-aged suicide attempters, but less often in older persons. DESIGN: Case-control study. SETTING: Community and university hospital. PARTICIPANTS: All participants were aged 65 and older. Thirty-five persons with a lifetime history of suicide attempts and depressive disorder were compared with 52 individuals with a past history of depressive disorder but no history suicidal acts, and 43 healthy comparison subjects. MEASUREMENTS: The Iowa Gambling Task was used as a measure of value-based decision-making. RESULTS: Taking into account age, sex, and Beck depression scores, no difference in decision-making performance was found between the three groups. The group of suicide attempters exhibited a significant heterogeneity, however, with those using violent means performing worse than non violent attempters. CONCLUSIONS: This study does not confirm the hypothesis of a significant role for poor Iowa Gambling Task performance as a general marker of suicidal behavior among the elderly but highlights its association with the specific subtype of violent suicidal attempters. Combined with previous findings among other age groups, it suggests that Iowa Gambling Task impairment may be a risk marker of vulnerability to violent suicidal acts. Future prospective studies should assess if this may represent a risk marker for suicide completion. PMID- 26905045 TI - Reaction Time Measures Predict Incident Dementia in Community-Living Older Adults: The Sydney Memory and Ageing Study. AB - OBJECTIVE: To examine the utility of intraindividual variability of reaction times (IIVRT) and mean reaction time (RT) as behavioral markers of incident all cause dementia. METHODS: A longitudinal cohort study followed biennially for 4 years, the community-based Sydney Memory and Ageing Study, 861 initially nondemented participants aged 70-90. Incident all-cause dementia determined by consensus, RT measures from simple and complex tasks, Mini-Mental State Exam and neuropsychological tests, Geriatric Depression Scale and Goldberg Anxiety Scale, cardiovascular risk score, apolipoprotein epsilon4 status, and the Bayer ADL Scale were used. Associations of baseline IIVRT and mean RT with time to dementia were evaluated with hazard ratios (HRs) using Cox proportional-hazards models with and without controlling for dementia risk factors. RESULTS: Forty-eight cases developed dementia. Greater complex IIVRT predicted a 40% (HR: 1.43) and mean RT a 50%-60% (simple RT: HR 1.53; complex RT: HR 1.59) per standard deviation increased risk of developing dementia, remaining significant after controlling for age, education, sex, general cognitive function, mood, cerebrovascular disease, and genetic susceptibility. Prediction of incident dementia using demographical information and RT measures combined was comparable with several traditional neuropsychological measures (AUC 0.75), although lower than a full neuropsychological battery (AUC 0.90). Prediction of functional decline by RT measures combined was equal to the neuropsychological battery (multiple Rs of .233 and .238, respectively). CONCLUSION: Brief RT measures provided information on risk of imminent dementia and functional decline within 4 years in older adults at a population level, with mean RT the stronger predictor. PMID- 26905044 TI - "Engage" Therapy: Behavioral Activation and Improvement of Late-Life Major Depression. AB - OBJECTIVE: Engage is a treatment for late-life depression developed to match the skills of community clinicians based on the theory that dysfunction in the Research Domain Criteria Project positive valence systems is a critical mechanism of late-life depression. Accordingly, it uses "reward exposure" (engagement in meaningful, rewarding activities) as its principal intervention. This study tests the hypothesis that change in behavioral activation, an index of positive valence systems function, during successive treatment periods with Engage and during follow-up predicts depression at the end of each period. METHODS: Forty-eight nondemented, older adults with unipolar major depression were treated openly with 9 weekly sessions of Engage and assessed 36 weeks after entry. Depression severity was assessed with the 24-item Hamilton Depression Rating Scale (HAM-D) and behavioral activation with the Behavioral Activation for Depression Scale (BADS) at baseline, 6 weeks (mid-treatment), 9 weeks (end of treatment), and 36 weeks. RESULTS: A mixed-effects model examined whether change in BADS in successive periods occurring during Engage treatment and during follow-up predicts depression at the end of each period. Both BADS change (F1,52 = 18.63, p < 0.0001) and time (F2,52 = 7.68, p = 0.0012) predicted HAM-D scores at the end of each observation period. Every point of increase in BADS change reduced the HAM-D by 0.105 points. HAM-D at each point did not predict subsequent change in BADS (F1,52 = 2.17, p = 0.146). CONCLUSION: During Engage treatment and follow up, change in behavioral activation is followed by improvement of depressive symptoms and signs. PMID- 26905046 TI - Posttraumatic Stress Disorder and Aging. PMID- 26905047 TI - The impact of psychotic symptoms on the persons with dementia experiencing them. AB - OBJECTIVE: To portray the emotional and behavioral reactions of persons with dementia to the delusions and hallucinations they experience, according to the reports of their family caregivers. The article also explores the relationship between those reactions and background variables. METHODS: Study participants were family caregivers of 74 older persons with a diagnosis of dementia (aged >= 65) residing in the community recruited from adult day centers and support groups for caregivers of persons with dementia and by advertising online. Assessments included the Behavioral Pathology in Alzheimer's Disease, the Neuropsychiatric Inventory, the Etiological Assessment of Psychotic Symptoms in Dementia, Activities of Daily Living questionnaire, and the Mini-Mental State Examination. RESULTS: Findings concerning emotional reactions reveal that close to half of the delusions resulted in discomfort, whereas around 40% did not. We found significant differences in the discomfort associated with different types of delusions, with delusions of abandonment, danger, and infidelity associated with more discomfort than other delusions. Around half of the delusions were associated with a behavioral manifestation. CONCLUSION: The findings highlight the need to examine the emotional impact of delusions and hallucinations as part of their assessment and as a consideration in treatment decisions. PMID- 26905048 TI - The Mental Health of Older Persons After Human-Induced Disasters: A Systematic Review and Meta-Analysis of Epidemiological Data. AB - BACKGROUND: Older people are increasingly "in harm's way" following human-induced disasters (HIDs). There is debate in the literature as to the relative impact of disasters on their psychological health compared with other age groups. Natural disasters and HIDs are thought to affect survivors differentially, and this may extend to older adults as a group. In the absence of existing systematic reviews, we aimed to synthesize the available evidence and conduct meta-analyses of the effects of HIDs on the psychological health of older versus younger adults. METHODS: A meta-analysis was conducted on papers identified through a systematic review. The primary outcomes measured were post-traumatic stress disorder (PTSD), depression, anxiety disorders, adjustment disorder, and psychological distress. RESULTS: We identified 11 papers from 10 studies on HIDs (N = 26,753), of which 8 had sufficient data for a random-effects meta-analysis. Older adults were 2.85 times less likely to experience PTSD symptoms following HID (95% CI: 1.42-5.70) when compared with younger adults. There was no statistically significant difference in terms of anxiety and depressive symptoms. CONCLUSION: Health and emergency services need to be increasingly prepared to meet the psychological needs of older people, given the global rise in the numbers of older adults affected by disasters of all kinds. Preliminary evidence suggests that old age may be a protective factor for the development of PTSD in the wake of HID. PMID- 26905049 TI - Effects of Transient Versus Chronic Loneliness on Cognitive Function in Older Adults: Findings From the Chinese Longitudinal Healthy Longevity Survey. AB - OBJECTIVES: Loneliness is a risk factor for poor cognitive function in older adults (OAs); to date, however, no studies have explored whether transient and chronic loneliness have differential effects on OAs' cognitive function. The present study evaluates the impacts of transient versus chronic loneliness on cognitive function in OAs. DESIGN: A 6-year follow-up cohort study. SETTING: Rural and urban communities of 22 provinces in China. PARTICIPANTS: 2,995 OAs who were cognitively healthy (the modified Mini-Mental State Examination [mMMSE] >= 14) and completed the 2005, 2008, and 2011 waves of the Chinese Longitudinal Healthy Longevity Survey. MEASUREMENTS: Self-report loneliness and mMMSE. RESULTS: Both transient (beta = -0.389, t = -2.191, df = 2994, p = 0.029) and chronic loneliness (beta = -0.640, t = -2.109, df = 2994, p = 0.035) were significantly associated with lower mMMSE scores 6 years later, net of potential confounding effects of baseline covariates. Sensitivity analyses found that regression coefficients of mMMSE scores on transient loneliness were statistically significant and relatively stable across samples with various levels of cognitive function. In contrast, coefficients of mMMSE scores on chronic loneliness were statistically significant only among samples with normal cognitive function and the absolute values of these coefficients increased with the degree of cognitive health of the analytic sample. In the sample with mMMSE greater than or equal to 21, the coefficient of chronic loneliness was 2.59 times as large as that of transient loneliness (-1.017 versus -0.392). CONCLUSIONS: Both transient and chronic loneliness are significant predictors of cognitive decline in OAs. Relative to transient loneliness, chronic loneliness has more pronounced negative effects on the brain health of OAs. PMID- 26905050 TI - Mental Fatigability and Heart Rate Variability in Mild Cognitive Impairment. AB - OBJECTIVES: Adaptive physiological stress regulation is rarely studied in mild cognitive impairment (MCI). Here we targeted mental fatigability (MF) as a determinant of altered high frequency heart rate variability (HF-HRV) reactivity in individuals with MCI, and examined frontobasal ganglia circuitry as a neural basis supporting the link between MF and HF-HRV reactivity. METHODS: We measured mental fatigability and HF-HRV during a 60-minute cognitive stress protocol in 19 individuals with MCI. HF-HRV responses were modeled using a quadratic equation. Resting state functional connectivity of intra- and inter-network frontobasal ganglia circuitry was assessed using blood-oxygen-level-dependent magnetic resonance imaging among seven of the participants. RESULTS: Lower MF was associated with faster and greater rebound in U-shape HF-HRV reactivity, which linked to a stronger connectivity between right middle frontal gyrus and left putamen. CONCLUSIONS: Results suggest that MF may contribute to abnormal physiological stress regulation in MCI, and fronto basal ganglia circuitry may support the link. PMID- 26905051 TI - Impact of lean six sigma process improvement methodology on cardiac catheterization laboratory efficiency. AB - BACKGROUND: Operational inefficiencies are ubiquitous in several healthcare processes. To improve the operational efficiency of our catheterization laboratory (Cath Lab), we implemented a lean six sigma process improvement initiative, starting in June 2010. We aimed to study the impact of lean six sigma implementation on improving the efficiency and the patient throughput in our Cath Lab. METHODS: All elective and urgent cardiac catheterization procedures including diagnostic coronary angiography, percutaneous coronary interventions, structural interventions and peripheral interventions performed between June 2009 and December 2012 were included in the study. Performance metrics utilized for analysis included turn-time, physician downtime, on-time patient arrival, on-time physician arrival, on-time start and manual sheath-pulls inside the Cath Lab. RESULTS: After implementation of lean six sigma in the Cath Lab, we observed a significant improvement in turn-time, physician downtime, on-time patient arrival, on-time physician arrival, on-time start as well as sheath-pulls inside the Cath Lab. The percentage of cases with optimal turn-time increased from 43.6% in 2009 to 56.6% in 2012 (p-trend<0.001). Similarly, the percentage of cases with an aggregate on-time start increased from 41.7% in 2009 to 62.8% in 2012 (p trend<0.001). In addition, the percentage of manual sheath-pulls performed in the Cath Lab decreased from 60.7% in 2009 to 22.7% in 2012 (p-trend<0.001). CONCLUSIONS: The current longitudinal study illustrates the impact of successful implementation of a well-known process improvement initiative, lean six sigma, on improving and sustaining efficiency of our Cath Lab operation. After the successful implementation of this continuous quality improvement initiative, there was a significant improvement in the selected performance metrics namely turn-time, physician downtime, on-time patient arrival, on-time physician arrival, on-time start as well as sheath-pulls inside the Cath Lab. PMID- 26905052 TI - Outcome of everolimus eluting bioabsorbable vascular scaffold (BVS) compared to non BVS drug eluting stent in the management of ST-segment elevation myocardial infarction (STEMI) - A comparative study. AB - BACKGROUND: The safety and efficacy of everolimus eluting bioabsorbable vascular scaffold (BVS) in the management of "ST" segment elevation myocardial infarction (STEMI) are yet to be established. AIMS: To evaluate immediate and short term safety and efficacy of the everolimus-eluting ABSORB BVS compared with non BVS drug eluting stent (DES) in patients with STEMI. METHODS: From December 2013 to December 2014, 220 patients with STEMI were included in this study. Among them, 35 patients treated with BVS were compared with a control group composed of 180 patients who underwent non BVS DES implantation in the same time period. The incidence of major adverse cardiac events (MACE: stent thrombosis: death, non fatal myocardial infarction, or target vessel/lesion revascularization) before discharge and up to six months was evaluated. RESULTS: 1 vessel disease was more frequent whereas, 2 and 3 vessel disease was less frequent in BVS group. Procedural characteristics were also similar between groups, except for the use of post dilation (p=0.04). Procedural success, in-hospital, and up to six-month MACE rates were similar between both groups. Definite or probable stent thrombosis did not occur (according to the ARC criteria) in BVS patients, though two patients during the index admission and another two patients in the first month after DES implantation had stent thrombosis. CONCLUSION: The use of the ABSORB BVS for STEMI is feasible and associated with good procedural safety, and angiographic success rate. PMID- 26905053 TI - Optical coherence tomography plaque characterization in a patient with ST segment elevation myocardial infarction after cocaine intake. AB - A 28-year old man presented to the Emergency Department with malaise after cocaine intake. After arrival he developed retrosternal chest pain and the electrocardiogram showed ST segment elevations in V1-V2 and ST segment depressions in V5-V6. An acute coronary angiogram revealed a focal non-occlusive lesion with thrombus in the left anterior descending artery. Supplementary optical coherence tomography (OCT) detected plaque erosion with adherent thrombus to be the responsible underlying pathophysiological mechanism. The patient received an effective antithrombotic regimen. Repeat angiogram with additional OCT one month later documented thrombus resolution and complete restoration of the previously eroded coronary vascular surface area. PMID- 26905054 TI - Absolute coronary blood flow measurement and microvascular resistance in ST elevation myocardial infarction in the acute and subacute phase. AB - BACKGROUND/PURPOSE: In a number of patients with acute myocardial infarction (AMI), myocardial hypoperfusion, known as the no-reflow phenomenon, persists after primary percutaneous intervention (PPCI). The aim of this study was to evaluate the feasibility and safety of a new quantitative method of measuring absolute blood flow and resistance within the perfusion bed of an infarct-related artery. Furthermore, we sought to study no-reflow by correlating these measurements to the index of microvascular resistance (IMR) and the area at risk (AR) as determined by cardiac magnetic resonance imaging (CMR). METHODS: Measurements of absolute flow and myocardial resistance were performed in 20 patients with ST-segment elevation myocardial infarction (STEMI), first immediately following PPCI and then again after 3-5days. These measurements used the technique of thermodilution during a continuous infusion of saline. Flow was expressed in ml/min per gram of tissue within the area at risk. RESULTS: The average time needed for measurement of absolute flow, resistance and IMR was 20min, and all measurements could be performed without complication. A higher flow supplying the AR correlated with a lower IMR in the acute phase. Absolute flow increased from 3.14 to 3.68ml/min/g (p=0.25) and absolute resistance decreased from 1317 to 1099 dyne.sec.cm-5/g (p=0.40) between the first day and fifth day after STEMI. CONCLUSIONS: Measurement of absolute flow and microvascular resistance is safe and feasible in STEMI patients and may allow for a better understanding of microvascular (dys)function in the early phase of AMI. PMID- 26905056 TI - Corrigendum. PMID- 26905055 TI - Serum biomarkers and source of inflammation in acute coronary syndromes and percutaneous coronary interventions. AB - There is robust information that confirms the enormous contribution of inflammation to plaque development, progression and vulnerability. The presence of plaques with inflammatory components associates with a greater likelihood of future cardiovascular events. The inflammatory cascade has been implicated during the entire plaque formation, from the early stages of endothelial dysfunction to the development of acute coronary syndromes (ACS). The presence of macrophages, T lymphocytes, dendritic cells, and mast cells in atherosclerotic lesions; the detection of HLA class II antigen expression; and the finding of secretion of several cytokines point to the involvement of immune inflammatory mechanisms in the pathogenesis of atherosclerosis. Serum biomarkers reflecting the activity of biological processes involved in plaque growth or destabilization may provide great help in establishing the appropriate clinical management, and therapeutic interventions. Evidence for a role of inflammation in plaque rupture has been demonstrated by localization of inflammation at plaque rupture sites. However, the focus of inflammation may not precisely reside within the coronary vessel itself but rather in the injured myocardium distal to the disrupted plaque. These observations outline the potential benefits of therapies targeting inflammation in the arterial wall and cardiovascular system. Emerging anti-inflammatory approaches to vascular protection have the potential to benefit patients by marked reductions in serum biomarkers of inflammation and reduce vascular events. With ongoing technical advances, percutaneous coronary interventions (PCI) will continue to play a critical role in the evaluation of novel compounds designed to modulate inflammation. The constant refinements in the different therapeutic strategies, the combination of scientific understanding in the adequate utilization of novel inflammatory markers, the new pharmacologic agents, and the new techniques in PCI will ameliorate our therapeutic management in ACS based on medical evidence. PMID- 26905057 TI - Strongyloides infection in rodents: immune response and immune regulation. AB - The human pathogenic nematode Strongyloides stercoralis infects approximately 30 100 million people worldwide. Analysis of the adaptive immune response to S. stercoralis beyond descriptive studies is challenging, as no murine model for the complete infection cycle is available. However, the combined employment of different models each capable of modelling some features of S. stercoralis life cycle and pathology has advanced our understanding of the immunological mechanisms involved in host defence. Here we review: (i) studies using S. stercoralis third stage larvae implanted in diffusion chambers in the subcutaneous tissue of mice that allow analysis of the immune response to the human pathogenic Strongyloides species; (ii) studies using Strongyloides ratti and Strongyloides venezuelensis that infect mice and rats to extend the analysis to the parasites intestinal life stage and (iii) studies using S. stercoralis infected gerbils to analyse the hyperinfection syndrome, a severe complication of human strongyloidiasis that is not induced by rodent specific Strongyloides spp. We provide an overview of the information accumulated so far showing that Strongyloides spp. elicits a classical Th2 response that culminates in different, site specific, effector functions leading to either entrapment and killing of larvae in the tissues or expulsion of parasitic adults from the intestine. PMID- 26905059 TI - Perenosins: a new class of anion transporter with anti-cancer activity. AB - A new class of anion transporter named 'perenosins' consisting of a pyrrole linked through an imine to either an indole, benzimidazole or indazole is reported. The indole containing members of the perenosin family function as effective transmembrane Cl(-)/NO3(-) antiporters and HCl cotransporters in a manner similar to the prodigiosenes. The compounds reduce the viability of MDA-MB 231 and MCF-7. PMID- 26905058 TI - Quantitative Histomorphometry of the Healthy Peritoneum. AB - The peritoneum plays an essential role in preventing abdominal frictions and adhesions and can be utilized as a dialysis membrane. Its physiological ultrastructure, however, has not yet been studied systematically. 106 standardized peritoneal and 69 omental specimens were obtained from 107 patients (0.1-60 years) undergoing surgery for disease not affecting the peritoneum for automated quantitative histomorphometry and immunohistochemistry. The mesothelial cell layer morphology and protein expression pattern is similar across all age groups. Infants below one year have a thinner submesothelium; inflammation, profibrotic activity and mesothelial cell translocation is largely absent in all age groups. Peritoneal blood capillaries, lymphatics and nerve fibers locate in three distinct submesothelial layers. Blood vessel density and endothelial surface area follow a U-shaped curve with highest values in infants below one year and lowest values in children aged 7-12 years. Lymphatic vessel density is much lower, and again highest in infants. Omental blood capillary density correlates with parietal peritoneal findings, whereas only few lymphatic vessels are present. The healthy peritoneum exhibits major thus far unknown particularities, pertaining to functionally relevant structures, and subject to substantial changes with age. The reference ranges established here provide a framework for future histomorphometric analyses and peritoneal transport modeling approaches. PMID- 26905060 TI - Dilute-As AlNAs Alloy for Deep-Ultraviolet Emitter. AB - The band structures of dilute-As AlNAs alloys with As composition ranging from 0% up to 12.5% are studied by using First-Principle Density Functional Theory (DFT) calculation. The energy band gap shows remarkable reduction from 6.19 eV to 3.87 eV with small amount of As content in the AlNAs alloy, which covers the deep ultraviolet (UV) spectral regime. A giant bowing parameter of 30.5 eV +/- 0.5 eV for AlNAs alloy is obtained. In addition, our analysis shows that the crossover between crystal field split-off (CH) band and heavy hole (HH) bands occurs in the dilute-As AlNAs alloy with As-content of ~1.5%. This result implies the possibility of dominant transverse electric (TE)-polarized emission by using AlNAs alloy with dilute amount of As-content. Our findings indicate the potential of dilute-As AlNAs alloy as the new active region material for TE-polarized III Nitride-based deep UV light emitters. PMID- 26905062 TI - Teaching Through Remembering: Using Written Reminiscences in Courses for Older Adults. AB - This article presents the use of reminiscence work in educational courses for older adults. The author analyzes a course that addresses experiences of time and the process of remembering at a later age. The study demonstrates how reminiscences, written by participants of the course, are used as illustrative material for some of the theoretical points. They are also instrumental in unfolding an answer to one of the key questions of the course, which is, what is the meaning of remembering in later life? The author argues that an educative use of personal reminiscences can improve the insight of the participants in theoretical issues at hand and can help them to develop new social skills, thus enabling them to translate experiences of aging into a sense-making process in later life. In addition, an educational application of reminiscence work broadens the possibilities for the participants to strengthen their feeling of belonging and to reach beyond one dominant version of history. PMID- 26905061 TI - Clinical characteristics, angiographic findings, and one-year outcome of 101 consecutive stent thrombosis cases in British Columbia. AB - BACKGROUND: Stent thrombosis (ST) is rare, but is associated with significant morbidity and mortality. METHODS: We analyzed data from the British Columbia (BC) Registry from April 2011-January 2012. RESULTS: 101 ST cases were reported and verified. Based on timing, ST was considered early (<=30days) in 35.6%, late (>30days-1year) in 17.8% and very late (>1year) in 46.5%. The majority (68.5%) presented with STEMI, and the remaining with non-STEMI (31.5%). Most vessels were functionally occluded (TIM1 flow grade <=1 in 67.1%). Thrombus burden was high (TIMI thrombus grade >=4 in 77.2%). Aspiration thrombectomy was performed in 41% of cases. New stents were implanted in 62.4% cases. Intra-coronary imaging was low (11%). At the original stent implantation, STEMI was the clinical presentation in 39.6%, the lesion was complex in 62.1%, and thrombus was visualized in 23.0%. Prognosis after ST was unfavorable with high mortality (11.9% at 30days and 16.8% at one year), and further revascularization (5.0% repeat PCI and 6.9% coronary artery bypass graft surgery). Early ST was associated with worse clinical outcome compared to late/very late ST: 30-day mortality at 22.2% versus 6.2% (p=0.02), and 1-year mortality at 27.8% versus 10.8% (p=0.05). CONCLUSIONS: In this prospective registry from BC, all ST presented with myocardial infarction, and the majority was treated with emergency PCI. Additional stents were commonly implanted with infrequent use of intracoronary imaging. Mortality rate was higher for early ST in comparison with late/very late ST. A comprehensive approach should be developed to treat this difficult complication. PMID- 26905063 TI - Estimated Effects of Different Alcohol Taxation and Price Policies on Health Inequalities: A Mathematical Modelling Study. AB - INTRODUCTION: While evidence that alcohol pricing policies reduce alcohol-related health harm is robust, and alcohol taxation increases are a WHO "best buy" intervention, there is a lack of research comparing the scale and distribution across society of health impacts arising from alternative tax and price policy options. The aim of this study is to test whether four common alcohol taxation and pricing strategies differ in their impact on health inequalities. METHODS AND FINDINGS: An econometric epidemiological model was built with England 2014/2015 as the setting. Four pricing strategies implemented on top of the current tax were equalised to give the same 4.3% population-wide reduction in total alcohol related mortality: current tax increase, a 13.4% all-product duty increase under the current UK system; a value-based tax, a 4.0% ad valorem tax based on product price; a strength-based tax, a volumetric tax of L0.22 per UK alcohol unit (= 8 g of ethanol); and minimum unit pricing, a minimum price threshold of L0.50 per unit, below which alcohol cannot be sold. Model inputs were calculated by combining data from representative household surveys on alcohol purchasing and consumption, administrative and healthcare data on 43 alcohol-attributable diseases, and published price elasticities and relative risk functions. Outcomes were annual per capita consumption, consumer spending, and alcohol-related deaths. Uncertainty was assessed via partial probabilistic sensitivity analysis (PSA) and scenario analysis. The pricing strategies differ as to how effects are distributed across the population, and, from a public health perspective, heavy drinkers in routine/manual occupations are a key group as they are at greatest risk of health harm from their drinking. Strength-based taxation and minimum unit pricing would have greater effects on mortality among drinkers in routine/manual occupations (particularly for heavy drinkers, where the estimated policy effects on mortality rates are as follows: current tax increase, -3.2%; value-based tax, 2.9%; strength-based tax, -6.1%; minimum unit pricing, -7.8%) and lesser impacts among drinkers in professional/managerial occupations (for heavy drinkers: current tax increase, -1.3%; value-based tax, -1.4%; strength-based tax, +0.2%; minimum unit pricing, +0.8%). Results from the PSA give slightly greater mean effects for both the routine/manual (current tax increase, -3.6% [95% uncertainty interval (UI) -6.1%, -0.6%]; value-based tax, -3.3% [UI -5.1%, -1.7%]; strength based tax, -7.5% [UI -13.7%, -3.9%]; minimum unit pricing, -10.3% [UI -10.3%, 7.0%]) and professional/managerial occupation groups (current tax increase, -1.8% [UI -4.7%, +1.6%]; value-based tax, -1.9% [UI -3.6%, +0.4%]; strength-based tax, 0.8% [UI -6.9%, +4.0%]; minimum unit pricing, -0.7% [UI -5.6%, +3.6%]). Impacts of price changes on moderate drinkers were small regardless of income or socioeconomic group. Analysis of uncertainty shows that the relative effectiveness of the four policies is fairly stable, although uncertainty in the absolute scale of effects exists. Volumetric taxation and minimum unit pricing consistently outperform increasing the current tax or adding an ad valorem tax in terms of reducing mortality among the heaviest drinkers and reducing alcohol related health inequalities (e.g., in the routine/manual occupation group, volumetric taxation reduces deaths more than increasing the current tax in 26 out of 30 probabilistic runs, minimum unit pricing reduces deaths more than volumetric tax in 21 out of 30 runs, and minimum unit pricing reduces deaths more than increasing the current tax in 30 out of 30 runs). Study limitations include reducing model complexity by not considering a largely ineffective ban on below tax alcohol sales, special duty rates covering only small shares of the market, and the impact of tax fraud or retailer non-compliance with minimum unit prices. CONCLUSIONS: Our model estimates that, compared to tax increases under the current system or introducing taxation based on product value, alcohol-content based taxation or minimum unit pricing would lead to larger reductions in health inequalities across income groups. We also estimate that alcohol-content-based taxation and minimum unit pricing would have the largest impact on harmful drinking, with minimal effects on those drinking in moderation. PMID- 26905064 TI - Aichi cohort study of the prognosis in patients newly initiated into dialysis (AICOPP): baseline characteristics and trends observed in diabetic nephropathy. AB - BACKGROUND: Over 300,000 patients receive maintenance dialysis in Japan; managing these patients is extremely important. This study aimed to report on prior management of chronic kidney diseases and prognostication after dialysis initiation. PATIENTS AND METHODS: Seventeen institutions participated in the Aichi cohort study of prognosis in patients newly initiated into dialysis and recruited patients over a period of 2 years. Exclusion criteria were (1) patients under 20 years; (2) patients who died before hospital discharge; and (3) patients who could not provide consent. RESULT: Here, we showed data on dialysis initiation time. Of 1524 patients with mean age of 67.5 +/- 13.0 years, 659 patients were put on dialysis following diabetic nephropathy diagnosis. At dialysis initiation time, creatinine and estimated glomerular filtration rate levels were 8.97 +/- 3.21 mg/dl and 5.45 +/- 2.22 ml/min/1.73 m2, respectively. Medications taken were angiotensin II receptor blockers in 866; angiotensin converting enzyme inhibitors in 135; calcium antagonist in 1202; and diuretics, alone or in combination, in 1059. Among patients with diabetic nephropathy, many had increased body weight and systolic blood pressure and were taking loop and thiazide diuretics at dialysis initiation time. Many patients with diabetic nephropathy had coronary artery disease and percutaneous coronary intervention. CONCLUSION: Many patients with diabetic nephropathy who registered for this study had coronary artery disease and problems with excess body fluid. Further analyses may clarify how underlying conditions and disease management before and after dialysis initiation affect prognosis. PMID- 26905065 TI - Spring viraemia of carp virus: recent advances. AB - Spring viraemia of carp is an environmentally and economically important disease affecting cyprinids, primarily common carp (Cyprinus carpio). The causative agent of this disease is Spring viraemia of carp virus (SVCV) - a member of the genus Vesiculovirus of the family Rhabdoviridae. The disease is presently endemic in Europe, America and several Asian countries, where it causes significant morbidity and mortality in affected fish. SVCV infection is generally associated with exophthalmia; abdominal distension; petechial haemorrhage of the skin, gills, eyes and internal organs; degeneration of the gill lamellae; a swollen and coarse-textured spleen; hepatic necrosis; enteritis; and pericarditis. The SVCV genome is composed of linear, negative-sense, ssRNA containing five genes in the order 3'-N-P-M-G-L-5', encoding a nucleoprotein, phosphoprotein, matrix protein, glycoprotein and RNA-dependent RNA polymerase, respectively. Fully sequenced SVCV strains exhibit distinct amino acid substitutions at unique positions, which may contribute to as-yet unknown strain-specific characteristics. To advance the study of SVCV and the control of spring viraemia of carp disease in the future, this review summarizes our current understanding of SVCV in terms of its genomic characteristics, genetic diversity and pathogenesis, and provides insights into antiviral immunity against SVCV, diagnosis of SVCV and vaccination strategies to combat SVCV. PMID- 26905066 TI - Rehabilitation after anatomical ankle ligament repair or reconstruction. AB - The selection, implementation of and adherence to a post-operative regimen are all essential in order to achieve the best outcomes after ankle ligament surgery. The purpose of this paper is to present a best-evidence approach to this, with grounding in basic science and a consensus opinion from the members of the ESSKA AFAS Ankle Instability Group. Basic science and clinical evidence surrounding tissue healing after surgical repair or reconstruction of the ligaments as well as around the re-establishment of sensorimotor control are reviewed. A consensus opinion based on this evidence as to the recommended rehabilitation protocol after ankle ligament surgery was then obtained from the members of the ESSKA-AFAS Ankle Instability Group. Rehabilitation recommendations are presented for the initial post-operative period, the early recovery phase and a goal-orientated late rehabilitation and return-to-sport phase. This paper presents practical, evidenced-based guidelines for rehabilitation and return to activity after lateral ankle ligament surgery. PMID- 26905067 TI - Cervical Cytology Specimen Stability in Surepath Preservative and Analytical Sensitivity for HPV Testing with the cobas and Hybrid Capture 2 Tests. AB - None of the commercial HPV tests are U.S. FDA-approved for testing of cervical cytology specimens in SurePath preservative. Still, ~30% of HPV testing is performed on specimens in this formalin-containing preservative. Formalin-induced DNA fragmentation and cross-linking may interfere with HPV detection. We evaluated analytical sensitivity and specimen stability of the cobas 4800 HPV (Roche) and Hybrid Capture 2 HPV (HC2, Qiagen) tests with residual cervical cytology samples in SurePath preservative available within 1 week of collection. Cobas testing was performed with and without heating samples at 120 degrees C for 20 min diluted 1:1 in an alkaline environment (pretreatment) to revert DNA crosslinking. Stability was tested after 2 weeks of storage at ambient temperature followed by <=10 weeks at 4 degrees C. Analytical sensitivity and positivity rates (HC2, 18%; cobas pretreated, 46%; cobas untreated, 47%) were greater for cobas than HC2 (n = 682). After 6 weeks of storage, mean HC2 ratios were lower (mean 0.9, SD 6.3) but high variability limited statistical power to detect trends. Cobas threshold cycles (Ct's) increased in untreated (mean 2.1) but not pretreated samples (mean 0.3; n = 110; p<=0.0001). Overall, cobas had greater analytical sensitivity for samples in SurePath preservative. Although pretreatment introduced a manual sample transfer step and 30 min of incubation times, it improved stability without negatively affecting analytical sensitivity. While awaiting results of large trials to evaluate the clinical performance of cobas, the addition of the pretreatment step may improve the detection of HPV, especially after prolonged sample storage. PMID- 26905068 TI - Multiple endocrine neoplasia type 1 syndrome: single centre experience from western India. AB - Multiple endocrine neoplasia type 1 syndrome (MEN1) is a rare autosomal dominant familial cancer syndrome affecting multiple endocrine glands. Published literature on MEN1 from Indian subcontinent is scarce. We report here a case series of MEN1 patients (n = 18) from 14 unrelated families. Retrospective study describing the clinical profile of MEN1 patients from endocrine unit of a tertiary care hospital from western India. Additionally clinical profile of primary hyperparathyroidism (PHPT) in MEN1 patients was compared with that of apparently sporadic PHPT cohort from our centre. Eighteen patients (10 males, 8 females) diagnosed as MEN1 were included. Mean age at diagnosis was 31.5 +/- 10.6 years (range 17-54). Incidence of primary hyperparathyroidism (PHPT), pituitary adenoma (PA), and gastro-entero-pancreatic neuroendocrine tumor (GEP-NET) was 94.4, 72.2, and 72.2 %, respectively. GEP-NET was the commonest presenting lesion (33.3 %), followed by PA (27.7 %), PHPT (16.6 %), thymic carcinoid (5.5 %), while 16.6 % cases were identified on family screening. PHPT manifestations (clinical and biochemical) in MEN1 were less severe as compared to those of sporadic PHPT. Contrast enhanced computed tomography (CECT) and (68)Ga-DOTANOC PET/CT were equally sensitive (64.7 vs. 63.5 %) in identifying multiglandular parathyroid disease. Non functioning tumors (NFT) were the most common GEP-NET, followed by insulinoma (5/13, two were metastatic). (68)Ga-DOTANOC PET/CT had higher sensitivity in detecting GEP-NET lesions than CECT (100 vs. 62.5 %). The most common pituitary lesion was prolactinoma, and all were cabergoline responsive. Genetic analysis was available in 13 patients and 11 patients showed mutation in MEN1 gene. The clinical profile of MEN1 in Asian Indian patients is largely comparable to that reported in other cohorts. Peculiar findings of our cohort are predominance of GEP-NET as a presenting manifestation and relatively higher prevalence of insulinoma with higher occurrence of metastatic insulinoma. Clinical and biochemical profile of MEN1 associated PHPT is less severe than that of our sporadic PHPT. PMID- 26905069 TI - The Challenge of Treating Early-Stage Rheumatoid Arthritis: The Contribution of Mixed Treatment Comparison to Choosing Appropriate Biologic Agents. AB - BACKGROUND: Use of biologic drugs is approved for treatment in rheumatoid arthritis (RA), both in established disease and at the early stage of RA (ERA). Identification of ERA and an early therapeutic strategy would lead to greater clinical improvement. Only a few indirect comparisons of the efficacy of different biologic agents in established RA have been performed and, to date, no studies reporting direct comparisons have been performed in ERA. OBJECTIVE: The aim of this study was to compare, by use of a mixed treatment comparison (MTC), the efficacy profiles of biologic agents in ERA. METHODS: An extensive literature search was performed to identify results of randomized, controlled trials (RCTs) evaluating biologic agents at licensed doses to treat patients affected by ERA. The primary end points for the analysis were the American College of Rheumatology 20% improvement (ACR20), ACR50, and ACR70 responses from baseline to various times of follow-up. WinBUGS 1.4 software (MRC Biostatistics Unit, Cambridge, UK) was used to perform the analyses. The MTC results are reported as the relative risk of a response for every single treatment coadministered with methotrexate, versus methotrexate plus placebo, which was used as a comparator in all RCTs. RESULTS: Ten scientific papers met the study inclusion criteria and were included in the analysis. Data on the use of infliximab, adalimumab, etanercept, abatacept, golimumab, and rituximab were included. No studies reported on the use of certolizumab pegol or tocilizumab in ERA. All biologic agents coadministered with methotrexate proved to be more efficacious than methotrexate plus placebo in inducing ACR20, ACR50, and ACR70 responses. The biologic agent characterized by the highest probability of inducing an ACR70 response was adalimumab (33.28%). Etanercept was the biologic agent with the highest probability of inducing ACR20 and ACR50 responses, in comparison with all other biologic agents, with probability rates of 62.95 and 37.1%, respectively. CONCLUSION: In our analysis, adalimumab proved to be the biologic agent with the highest probability of inducing an ACR70 response in patients affected by ERA, while etanercept was the biologic agent with the highest probability of inducing ACR50 and ACR20 responses. PMID- 26905070 TI - Ancrod revisited: viscoelastic analyses of the effects of Calloselasma rhodostoma venom on plasma coagulation and fibrinolysis. AB - Fibrinogen depletion via catalysis by snake venom enzymes as a therapeutic strategy to prevent or treat thrombotic disorders was utilized for over four decades, with ancrod being the quintessential agent. However, ancrod eventually was found to not be of clinical utility in large scale stroke trial, resulting in the eventual discontinuation of the administration of the drug for any indication. It was hypothesized that ancrod, possessing thrombin-like activity, may have unappreciated robust coagulation kinetics. Using thrombelastographic methods, a comparison of equivalent tissue factor initiated thrombin generation and Calloselasma rhodostoma venom (rich in ancrod activity) on plasmatic coagulation kinetics was performed. The venom resulted in thrombi that formed nearly twice as fast compared to thrombin formed clots, and there was no difference in fibrinolytic kinetics initiated by tissue-type plasminogen activator. In plasma containing iron and carbon monoxide modified fibrinogen, which may be found in patients at risk of stroke, the coagulation kinetic differences observed with venom was still more vigorous than that seen with thrombin. These phenomena may provide insight into the clinical failure of ancrod, and may serve as an impetus to revisit the concept of fibrinogen depletion via fibrinogenolytic enzymes, not those with thrombin-like activity. PMID- 26905072 TI - Corneal Biomechanical Properties in Aspirin Users. AB - PURPOSE: To analyze corneal biomechanical properties in aspirin users using an ocular response analyzer. METHODS: This study included 80 eyes of 40 aspirin users and 80 eyes of 40 individuals who did not use aspirin. Corneal hysteresis (CH), the corneal resistance factor (CRF), Goldman-correlated intraocular pressure (IOPg), and corneal compensated intraocular pressure (IOPcc) were measured in all participants. The independent samples t test was used to compare measurements in the aspirin users and nonusers in the total study population, and in the diabetic patient subgroup. Pearson's correlation analysis was used to examine the relationship between the measured variables in the aspirin users and nonusers. RESULTS: Aspirin users (59.08 +/- 11.83 years) were older than nonusers (39.82 +/- 12.97 years; p < 0.001). The mean CH was significantly lower in the aspirin user group than in the nonuser group (p = 0.013). Mean IOPg and mean IOPcc were also significantly higher in the aspirin user group (p = 0.027 and p = 0.002, respectively). The mean CRF was lower in the aspirin user group, but not significantly (p = 0.70). There was a positive correlation between CH and CRF (r = 0.767, p < 0.001), and between CRF and IOPg (r = 0.680, p < 0.001), and a negative correlation between CH and IOPcc (r = -0.415, p < 0.001). CONCLUSIONS: Aspirin should be taken into account when interpreting the results of corneal biomechanical measurements. PMID- 26905073 TI - Stomach Cancer: Interconnection between the Redox State, Activity of MMP-2, MMP-9 and Stage of Tumor Growth. AB - High levels of reactive oxygen (ROS) and nitrogen (RNS) species can lead to the destruction of extracellular matrix facilitating tumor progression. ROS can activate matrix metalloproteinases (MMP), damage DNA and RNA. Therefore, the levels of MMP, ROS and RNS can serve as additional prognostic markers and for the estimation of the effectiveness of tumor therapy. Concerning gastric cancer, the prognostic role of MMP, its connection with the cancer staging remains controversial and correlations between the activity of MMP with the ROS and RNS levels are insufficiently confirmed. Superoxide generation rates, nitric oxide (NO) levels, concentrations of active forms of matrix metalloproteinases MMP-2 and MMP-9 in tumor and adjacent tissues of patients with stomach cancer at different disease stages were measured by electron spin resonance (ESR) including spin-trapping and polyacrylamide gel zymography. It is shown that the activity of MMP-2 and MMP-9 in tumor tissue correlate with the superoxide radicals generation rate and NO levels (r = 0.48/0.67, p < 0.05). The activity of MMP-2 and MMP-9 in tumor tissues and superoxide radical generation rates correlate positively with the stage of regional dissemination (r = 0.45 and 0.37, correspondingly, p < 0.05), but MMP-2 and MMP-9 activity inversely depends on distant metastatic degree of stomach cancer (r = 0.58; p < 0.05). Additionally, the feasibility of ESR to locally determine oxidative stress is demonstrated. PMID- 26905071 TI - Neurologic Complications of Commonly Used Drugs in the Hospital Setting. AB - This chapter reviews the neurologic complications of medications administered in the hospital setting, by class, introducing both common and less common side effects. Detail is devoted to the interaction between pain, analgesia, sedation, and their residual consequences. Antimicrobials are given in nearly every hospital setting, and we review their capacity to produce neurologic sequelae with special devotion to cefepime and the antiviral treatment of human immunodeficiency virus. The management of hemorrhagic stroke has become more complex with the introduction of novel oral anticoagulants, and we provide an update on what is known about reversal of the new oral anticoagulants. Both central and peripheral nervous system complications of immunosuppressants and chemotherapies are reviewed. Because diagnosis is generally based on clinical acumen, alone, neurotoxic syndromes resulting from psychotropic medications may be easily overlooked until severe dysautonomia develops. We include a practical approach to the diagnosis of serotonin syndrome and neuroleptic malignant syndrome. PMID- 26905074 TI - Cryptosporidium avium n. sp. (Apicomplexa: Cryptosporidiidae) in birds. AB - The morphological, biological, and molecular characteristics of Cryptosporidium avian genotype V are described, and the species name Cryptosporidium avium is proposed to reflect its specificity for birds under natural and experimental conditions. Oocysts of C. avium measured 5.30-6.90 MUm (mean = 6.26 MUm) * 4.30 5.50 MUm (mean = 4.86 MUm) with a length to width ratio of 1.29 (1.14-1.47). Oocysts of C. avium obtained from four naturally infected red-crowned parakeets (Cyanoramphus novaezealandiae) were infectious for 6-month-old budgerigars (Melopsittacus undulatus) and hens (Gallus gallus f. domestica). The prepatent periods in both susceptible bird species was 11 days postinfection (DPI). The infection intensity of C. avium in budgerigars and hens was low, with a maximum intensity of 5000 oocysts per gram of feces. Oocysts of C. avium were microscopically detected at only 12-16 DPI in hens and 12 DPI in budgerigars, while PCR analyses revealed the presence of specific DNA in fecal samples from 11 to 30 DPI (the conclusion of the experiment). Cryptosporidium avium was not infectious for 8-week-old SCID and BALB/c mice (Mus musculus). Naturally or experimentally infected birds showed no clinical signs of cryptosporidiosis, and no pathology was detected. Developmental stages of C. avium were detected in the ileum and cecum using scanning electron microscopy. Phylogenetic analyses based on small subunit rRNA, actin, and heat shock protein 70 gene sequences revealed that C. avium is genetically distinct from previously described Cryptosporidium species. PMID- 26905075 TI - High jugular bulb: different osseous landmarks and their clinical implications. AB - PURPOSE: The purpose of this investigation was to compare the rate of high jugular bulb (HJB) in relation to internal acoustic meatus (IAM), round window (RW) and endolymphatic sac and to study their clinical implications. METHODS: Eighty-seven cadaveric non-pathologic human temporal bones were micro-dissected to expose the jugular fossa (JF) and RW. The minimum distance of JF from RW was measured. On the inner surface of petrous part of temporal bone, minimum vertical distance of JF from IAM and saccus endolymphaticus (E sac) was also measured. If the distance of summit of JF from RW or IAM was <=2 mm or if there was no distance between JF and slit on which E sac opens, they were classified as HJB cases. RESULTS: The mean minimum distance of JF from the RW, IAM and E sac was found to be 2.85 +/- 1.58, 3.83 +/- 2.38 and 2.06 +/- 2.38 mm and the rate of HJB was 32.2, 24.1 and 41.4 % respectively. CONCLUSIONS: The rate of HJB varies even in a particular specimen using different landmarks i.e. the RW, IAM and E sac. The preoperative awareness in relation to these landmarks will be useful in cochlear implantation, surgical removal of vestibular schwanommas and clinical findings of Meniere's disease. PMID- 26905076 TI - Cone beam computed tomography of plastinated hearts for instruction of radiological anatomy. AB - Radiological anatomy education is an important aspect of the medical curriculum. The purpose of this study was to establish and demonstrate the use of plastinated anatomical specimens, specifically human hearts, for use in radiological anatomy education. Four human hearts were processed with routine plastination procedures at room temperature. Specimens were subjected to cone beam computed tomography and a graphics program (ER3D) was applied to generate 3D cardiac models. A comparison was conducted between plastinated hearts and their corresponding computer models based on a list of morphological cardiac features commonly studied in the gross anatomy laboratory. Results showed significant correspondence between plastinations and CBCT-generated 3D models (98 %; p < .01) for external structures and 100 % for internal cardiac features, while 85 % correspondence was achieved between plastinations and 2D CBCT slices. Complete correspondence (100 %) was achieved between key observations on the plastinations and internal radiological findings typically required of medical student. All pathologic features seen on the plastinated hearts were also visualized internally with the CBCT-generated models and 2D slices. These results suggest that CBCT-derived slices and models can be successfully generated from plastinated material and provide accurate representations for radiological anatomy education. PMID- 26905077 TI - MET mutations are associated with aggressive and radioresistant brain metastatic non-small-cell lung cancer. PMID- 26905078 TI - Genetic variations altering FSH action affect circulating hormone levels as well as follicle growth in healthy peripubertal girls. AB - STUDY QUESTION: Do variants of the genes encoding follicle stimulating hormone (FSH) beta subunit (B) and FSH receptor (R) impact circulating reproductive hormone levels and ovarian follicle maturation in healthy peripubertal girls? SUMMARY ANSWER: FSHB and FSHR genetic variants exert, alone or their combination, distinct effects on reproductive hormone levels as well as ovarian follicle maturation in healthy peripubertal girls. WHAT IS KNOWN ALREADY: FSHB and FSHR genetic variants impact reproductive hormone levels as well as associated pathologies in women. While FSHR c. 2039A>G is known to alter gonadotrophin levels in women, FSHR c.-29G>A has not yet been shown to exert effect and there are conflicting results concerning FSHB c.-211G>T. STUDY DESIGN, SIZE, DURATION: This population-based study included 633 girls recruited as part of two cohorts, the COPENHAGEN Puberty Study (2006-2014, a cross-sectional and ongoing longitudinal study) and the Copenhagen Mother-Child Cohort (1997-2002, including transabdominal ultrasound (TAUS) of the ovaries in a subset of 91 peripubertal girls). PARTICIPANTS/MATERIALS, SETTING, METHODS: Clinical examinations, including pubertal breast stage (Tanner's classification B1-B5) were performed. Circulating levels of FSH, luteinizing hormone (LH), estradiol, anti-Mullerian hormone (AMH) and inhibin-B were assessed by immunoassays. In a subset of the girls (n = 91), ovarian volume and the number/size of antral follicles were assessed by TAUS. Genotypes were determined by competitive PCR. MAIN RESULTS AND THE ROLE OF CHANCE: FSHR c.2039A>G minor alleles were positively associated with serum FSH (beta = 0.08, P = 0.004), LH (beta = 0.06, P = 0.012) and estradiol (beta = 0.06, P = 0.017) (adjusted for Tanner stages). In a combined model, FSHR c.-29G>A and FSHR c.2039A>G alleles were positively associated with FSH levels in early-pubertal girls (B2 + B3, n = 327, r = 0.1, P = 0.02) and in young adolescents (B4 + B5, n = 149, r = 0.2, P = 0.01). Serum AMH and inhibin B levels were not significantly influenced by the single nucleotide polymorphisms (SNPs). Single SNPs were not associated with follicles counts, however, a cumulative minor allele count (FSHB c.-211 G>T and FSHR c.-29G>A) was negatively associated with the number of large follicles (>=5 mm) (n = 91, P = 0.04) (adjusted for Tanner stages). LIMITATIONS, REASONS FOR CAUTION: Since we studied girls and young adolescents during pubertal transition, our study may not be fully comparable with previous studies on FSHB and FSHR variants in adult women. The group of young adolescents (Tanner B4 + B5) reflects the endocrine situation in adult women best, however, the group is not large enough to contribute substantially to the conflicting results concerning the influence of FSHB c. 211G>T in adult women. Furthermore, we have no information about the exact day of the menstrual cycle in the subgroup of girls with menarche. WIDER IMPLICATIONS OF THE FINDINGS: The sex-specific interaction of FSHB and FSHR genetic variants and physiological as well as pathological conditions is being increasingly elucidated. The variant triplet set might serve as diagnostic and pharmacogenetic marker. For the first time, we show an additional effect of FSHR c.-29G>A on serum FSH levels in healthy girls. Moreover, morphological data suggest impaired FSH-induced maturation of ovarian follicles in minor allele carriers of FSHB c. 211G>T and FSHR c.-29G>A. This may explain previous findings of delayed pubertal onset in these girls. STUDY FUNDING/COMPETING INTERESTS: Funding was provided by the Danish Agency for Science, Technology and Innovation (09-067180), Danish Ministry of the Environment, CeHoS (MST-621-00065), Capital Region of Denmark (December 2011), Ministry of Higher Education and Science (DFF-1331-00113) and EDMaRC (Danish Ministry of Health). A.S.B. was funded from December 2015 by ReproUnion (EU Interreg Oresund-Kattegat-Skagerrak). The authors declare no conflict of interest. PMID- 26905079 TI - Health information seeking and scanning among US adults aged 50-75 years: Testing a key postulate of the information overload model. AB - Past research has found that older US adults (aged 50-75 years) exhibit high levels of cancer information overload and cancer worry; however, no study to date has examined whether these perceptions are related to information seeking/scanning. To explore this relationship, older adults ( N = 209, Mage = 55.56, SD = 4.24) were recruited to complete a survey measuring seeking, scanning, cancer information overload, and cancer worry. Most participants were high-scan/seekers (40.2%) followed by low-scan/seekers (21.1%), high-scan/no seekers (19.6%), and low-scan/no seekers (19.1%). Low-scan/no seekers had significantly higher cancer information overload compared to all other groups, consistent with the postulate that overload and seeking/scanning are negatively related. Low-scan/no seekers and high-scan/seekers both exhibited higher cancer worry severity, consistent with past research suggesting that cancer worry explains high levels of activity/inactivity. PMID- 26905081 TI - Ditching our simplistic systems for categorising mental health problems. PMID- 26905080 TI - Client-perpetrated and husband-perpetrated violence among female sex workers in Andhra Pradesh, India: HIV/STI risk across personal and work contexts. AB - OBJECTIVES: This study examines violence experienced in work and personal contexts and relation to HIV risk factors in these contexts among female sex workers (FSW) in Andhra Pradesh, India. METHODS: FSW at least 18 years of age (n=2335) were recruited through three rounds of respondent-driven sampling between 2006 and 2010 for a survey on HIV risk. Using crude and adjusted logistic regression models, any sexual/physical violence (last 6 months) perpetrated by clients and husbands were separately assessed in association with accepting more money for sex without a condom (last 30 days), consistent condom use with clients and husbands (last 30 days), and sexually transmitted infection (STI) symptoms (last 6 months). RESULTS: The mean age among participants was 32, 22% reported being currently married, and 22% and 21% reported physical/sexual violence by clients and husbands, respectively. In adjusted logistic regression models, FSW who experienced client violence were more likely to report accepting more money for unprotected sex trades (adjusted OR (AOR)=1.7; 95% CI 1.4 to 2.2), less likely to report consistent condom use with clients (AOR=0.6; 95% CI 0.5 to 0.7) and more likely to report STI symptoms (AOR=3.5; 95% CI 2.6 to 4.6). Women who reported husband violence were more likely to report accepting more money for unprotected sex trades (AOR=2.1; 95% CI 1.2 to 3.7), less likely to report consistent condom use with clients (AOR=0.5; 95% CI 0.3 to 0.8) and more likely to report STI symptoms (AOR=2.6; 95% CI 1.6 to 4.1). CONCLUSIONS: Among FSW, experiences of violence in work and personal contexts are associated with sexual HIV risk behaviours with clients as well as STI symptoms. PMID- 26905082 TI - The efficiency of gait plate insole for children with in-toeing gait due to femoral antetorsion. AB - BACKGROUND: One of the most common gait disorders in children is in-toeing. Few studies have examined the efficacy gait plate insole in in-toeing. we used more precise apparatus than previous studies. OBJECTIVES: The aim of this study was to investigate the immediate effect of gait plate insole on the angle of gait and center of pressure displacement in children with in-toeing gait. STUDY DESIGN: Quasi-experimental before -after study. METHODS: The angle of gait and center of pressure displacement were measured in 17 children aged 4-10 years with in-toeing gait. The RS scan pressure platform was employed to perform walking tests in three conditions including barefoot, with shoes only, and gait plate insole with shoes. RESULTS: The gait plate insole with shoes as well as shoes alone produced a significant 11.1 degrees and 3.85 degrees increase in the angle of gait in in toeing children respectively ( p < 0.05). The medial-lateral displacement of center of pressure showed a significant difference (3 mm) in shoes only condition when compared with barefoot condition. The shoes only and gait plate insole compared with barefoot condition increased the anterior-posterior displacement by 28 and 30 mm respectively. CONCLUSION: The gait plate insole with ordinary shoes and shoes only were able to increase angle of gait and the center of pressure displacement in the anterior-posterior direction in children with in-toeing gait due to excessive femoral anteversion. Clinical relevance The use of a gait plate insole inserted in ordinary shoes can improve gait appearance in children with in toeing gait caused by Excessive femoral anteversion. PMID- 26905083 TI - Plasma cell panniculitis, a type of morphea profunda, surrounded by congenital nevus spilus. PMID- 26905084 TI - The origin of motoneuron synchronization. PMID- 26905085 TI - The common input notion, conceived and sustained by conjecture. PMID- 26905086 TI - Pollen competition in style: Effects of pollen size on siring success in the hermaphroditic common morning glory, Ipomoea purpurea. AB - PREMISE OF THE STUDY: Pollen size varies greatly among flowering plant species and has been shown to influence the delivery of sperm cells to the eggs. Relatively little is known, however, about the functional significance of within species genetic variation in pollen size. This study tests whether pollen size influences the relative siring success of a pollen donor during in vivo pollen competition experiments. METHODS: We used two groups of Ipomoea purpurea plants genetically divergent in their pollen sizes and applied equal number of pollen grains from one large-pollen and one small-pollen donor onto the same stigma. Using microsatellite genetic markers, we identified the pollen parent of each of the resulting progeny to determine the relative siring success of the competing donors. Competitions between donors of equal-sized pollen served as a control. KEY RESULTS: Differences in pollen size significantly affected the relative siring success of a pollen donor; larger-grained individuals outcompeted smaller grained competitors but not equal-sized competitors. Relative siring success, however, sometimes varied across different pollen recipients. CONCLUSIONS: Pollen size can influence the relative siring success of different individuals competing on the same stigma during postpollination processes. However, other factors, such as pollen-pistil interaction and environmental conditions, are likely to influence these competitions as well. PMID- 26905087 TI - Effects of virus infection on pollen production and pollen performance: Implications for the spread of resistance alleles. AB - PREMISE OF STUDY: Studies over the past 25 years have shown that environmental stresses adversely affect male function, including pollen production and pollen performance (germination and pollen tube growth rate). Consequently, genetic variation among plants in resistance to a stress has the potential to impact pollen donation to conspecifics and, if deposited onto a stigma, the ability of the pollen to achieve fertilization. We examined the effects of a nonlethal virus epidemic on pollen production and pollen performance in a population of susceptible and resistant (transgenic) wild squash (Cucurbita pepo subsp. texana). METHODS: We grew 135 susceptible and 45 virus-resistant wild squash plants in each of two 0.4-ha fields, initiated a zucchini yellow mosaic virus (ZYMV) epidemic, and recorded staminate and pistillate flower production per plant over the field season and the total number of mature fruit. We also assessed pollen production per flower on ZYMV-infected and non-infected plants and the ability of pollen from flowers on infected and non-infected plants to achieve fertilization under competitive conditions. KEY RESULTS: ZYMV infection reduced flower and fruit production per plant and pollen production per flower. Pollen from infected plants was also less likely to sire a seed under competitive conditions. CONCLUSIONS: ZYMV infection adversely impacts the amount of pollen that can be donated to conspecifics, and pollen competition within the styles increases the probability that the ovules are fertilized by pollen from plants that are thriving when challenged by a viral disease. PMID- 26905088 TI - Clinical Use of Silver Diamine Fluoride in Dental Treatment. AB - The use of a topical fluoride solution, namely silver diamine fluoride (SDF), in dental treatment has been drawing increasing attention. SDF has been used in some countries in Asia, including Japan and China, as a caries-arresting and anti hypersensitivity agent. It was recently cleared by the Food and Drug Administration in the United States as a fluoride to manage hypersensitive teeth. Topical application of SDF is a noninvasive procedure that is quick and simple to use. Promising results of laboratory studies and clinical trials have suggested that SDF is more effective than other fluoride agents to halt the caries process. A review concluded that SDF is a safe, effective, efficient, and equitable caries control agent that has a potentially broad application in dentistry and may meet the criteria of both the WHO Millennium Development Goals and the US Institute of Medicine's criteria for 21st century medical care. This article provides an overview of the clinical use of SDF in dental treatment. PMID- 26905089 TI - Gummy Smile and Short Tooth Syndrome--Part 1: Etiopathogenesis, Classification, and Diagnostic Guidelines. AB - Treating patients with "gummy smiles" and improving smile esthetics has become an integral part of dentistry. It is necessary to conduct an accurate diagnosis of what may be multiple causes that coexist simultaneously. Though all causes may not be resolved following treatment, they should be identified; otherwise it might not be possible to conduct an adequate order of treatment, which could involve multidisciplinary collaboration between various dental specialists, and may lead to unexpected and unacceptable final results. The authors propose a complete adult classification of the causes identified for gummy smile (GS) and short tooth syndrome (STS) to ascertain the etiopathogenetic origin(s). Used in combination with the proposed diagnostic procedure, which involves an "outside in" evaluation of the patient, the classification system will enable clinicians to provide patients an accurate prediction of final results and determine the treatment required. PMID- 26905090 TI - Treatment of a "Gummy Smile": Understanding Etiology is Key to Success. AB - When dealing with excessive gingival display it is important for the treating clinician to properly identify the etiology, as potential etiologic factors can vary widely. Treatment decisions in this case involving a patient with high lip dynamics and a "gummy smile" were complicated because treatment recommendations differed for each of the several etiologies involved. The treatment performed, which included orthodontics combined with crown lengthening and in which the final restorations were segmented anterior to posterior to give both the clinician and laboratory improved control, was designed to meet the patient's desired esthetic outcome while addressing the areas of risk established in the preoperative assessment. PMID- 26905091 TI - Retrofitting a Crown Supporting a Removable Partial Denture Using "Biogeneric Copy" to Replicate Tooth's Preoperative Condition. AB - When a crown that supports a removable partial denture (RPD) needs to be replaced, patients often balk at having to wait several weeks for laboratory production to be completed before receiving the new restoration. Moreover, the fit of the lab-produced unit may not always be satisfactory. CEREC(r) CAD/CAM technology provides a design method known as Biogenetic Copy, which allows a clinician to replicate the preexisting size, shape, and form of a tooth chairside. As this case report demonstrates, using this method to retrofit a crown under an existing RPD prosthesis can result in a predictable, accurate, durable, and esthetic same-day restorative solution. PMID- 26905092 TI - A Report of Three Cases from an Ongoing Prospective Clinical Study on a Novel Pink Biomimetic Implant System. AB - While, overall, dental implants are highly efficacious, consistently achieving predictable esthetic results can pose color-driven challenges at the implant/soft tissue interface, particularly in the esthetic zone. An ongoing, 5-year, multicenter (eight sites) prospective study is following a total of 168 implants placed in 120 patients using a novel biomimetic (osteoconductive) implant system with pink collars and abutments that afford better gingival color matching, enhanced design variability, and streamlined fabrication and customization of the abutment/implant-tissue interface. The full results of this study will be published at the 3-year and 5-year timepoints; however, clinical analyses of the 18-month interim survival rates, marginal bone and soft-tissue level changes, and esthetics have been completed, showing an overall success rate among all of the implanted sites of 95.8%. For the three representative cases described in this article (two anterior, one posterior), all of the implant site probing depths were <= 3 mm at the final crown placement as well as at 6, 12, and 18 months after implant placement. Facial soft-tissue heights were stable or increased by >= 0.86 mm; lingual soft-tissue heights were reduced by <= 1.11 mm. Facial and lingual attached-gingiva widths were reduced by <= 1.20 mm and <= 0.63 mm, respectively. Interproximal marginal alveolar bone levels were stable (gain/loss range: +0.40 to -1.1 mm) from the start of the study through 18 months. Gingival inflammation, bleeding on probing, and plaque were infrequently observed, and esthetic results were uniformly excellent at the 18-month follow-up visit. PMID- 26905093 TI - Structure-Dependent Spin Polarization in Polymorphic CdS:Y Semiconductor Nanocrystals. AB - Searching for the polymorphic semiconductor nanocrystals would provide precise and insightful structure-spin polarization correlations and meaningful guidance for designing and synthesizing high spin-polarized spintronic materials. Herein, the high spin polarization is achieved in polymorphic CdS:Y semiconductor nanocrystals. The high-pressure polymorph of rock-salt CdS:Y nanocrystals has been recovered at ambient conditions synthesized by the wurtzite CdS:Y nanocrystals as starting material under 5.2 GPa and 300 degrees C conditions. The rock-salt CdS:Y polymorph displays more robust room-temperature ferromagnetism than wurtzite sample, which can reach the ferromagnetic level of conventional semiconductors doped with magnetic transition-metal ions, mainly due to the significantly enhanced spin configuration and defect states. Therefore, crystal structure directly governs the spin configuration, which determines the degree of spin polarization. This work can provide experimental and theoretical methods for designing the high spin-polarized semiconductor nanocrystals, which is important for applications in semiconductor spintronics. PMID- 26905094 TI - Constituents of Fagraea fragrans with Antimycobacterial Activity in Combination with Erythromycin. AB - Seven new compounds constituted by three secoiridoids (1-3), two isocoumarins (4 and 5), an iridoid (6), and an aromatic derivative (7) in addition to 24 known compounds were isolated from the stem bark of Fagraea fragrans. The structures of the new compounds were determined on the basis of spectroscopic data analysis. The isolated compounds showed no antibacterial activity against Staphylococcus aureus and Escherichia coli. However, 5-formylisochromen-1-one (4), (-)-mellein (8), and swermacrolactone C (9) exhibited potent antimycobacterial activities against Mycobacterium smegmatis when used in combination with the antibiotic drug erythromycin. PMID- 26905095 TI - Dietary Acrylamide and the Risk of Endometrial Cancer: An Italian Case-Control. AB - The role of dietary acrylamide on the risk of hormone-related, and specifically endometrial, cancers is debated. Epidemiological data are scanty. Thus, we examined the relation between acrylamide intake and endometrial cancer risk in a case-control study conducted between 1992 and 2006 in 3 Italian areas. Cases were 454 women with incident, histologically confirmed endometrial cancer. Controls were 908 age-matched women admitted to the same network of hospitals of cases for acute, non-neoplastic conditions. We calculated multivariate odds ratios (OR) and 95% confidence intervals (CI) using logistic regression models. The OR of endometrial cancer for increasing quintiles of dietary acrylamide, as compared to the lowest one, were 1.02 (95% CI: 0.67-1.54), 1.20 (95% CI: 0.80-1.80), 1.00 (95% CI: 0.65-1.54) and 1.17 (95% CI: 0.73-1.85). The OR for an increase of 10 MUg/day of dietary acrylamide was 1.00 (95% CI: 0.91-1.10). In subgroup analyses, the ORs for high vs. low acrylamide intake were 1.28 (95% CI: 0.73-2.25) in never smokers and 1.14 (95% CI: 0.45-2.90) in ever smokers. Our data do not support an association between dietary acrylamide intake and endometrial cancer. PMID- 26905096 TI - Evaluation of the ability of bone marrow derived cells to engraft the kidney and promote renal tubular regeneration in mice following exposure to cisplatin. AB - It has been suggested that bone marrow derived stem cells have the ability to engraft the kidney and improve the outcome of severe acute kidney injury (AKI) in mice exposed to high doses of cisplatin, providing hope for cancer patients in whom irreversible renal damage occasionally occurs following the use of this highly effective anti-tumor drug. We tested the therapeutic potential of bone marrow derived cells injected during the acute phase (day 3 after cisplatin administration) of experimentally-induced AKI in C57Bl6/J mice, characterized by massive tubular necrosis, apoptosis, and a low proliferation capacity. We failed to show any benefit of bone marrow derived cells versus a regular homogenate of intact renal cells, or normal saline. Using cell tracers and flow cytometry, we demonstrated that bone marrow derived cells did indeed home to the bone marrow of the recipients but failed to settle in the kidney. Conversely, renal cells homed to injured kidneys. However, neither cell therapy protected the animals against cisplatin-induced death. We therefore question the short-term efficacy of bone marrow derived cells used to repair established injuries of the tubular epithelium. PMID- 26905097 TI - The Pendulum Swings for Opioid Prescribing. PMID- 26905099 TI - Update on Renal Replacement Therapy: Implantable Artificial Devices and Bioengineered Organs. AB - Recent advances in the fields of artificial organs and regenerative medicine are now joining forces in the areas of organ transplantation and bioengineering to solve continued challenges for patients with end-stage renal disease. The waiting lists for those needing a transplant continue to exceed demand. Dialysis, while effective, brings different challenges, including quality of life and susceptibility to infection. Unfortunately, the majority of research outputs are far from delivering satisfactory solutions. Current efforts are focused on providing a self-standing device able to recapitulate kidney function. In this review, we focus on two remarkable innovations that may offer significant clinical impact in the field of renal replacement therapy: the implantable artificial renal assist device (RAD) and the transplantable bioengineered kidney. The artificial RAD strategy utilizes micromachining techniques to fabricate a biohybrid system able to mimic renal morphology and function. The current trend in kidney bioengineering exploits the structure of the native organ to produce a kidney that is ready to be transplanted. Although these two systems stem from different technological approaches, they are both designed to be implantable, long lasting, and free standing to allow patients with kidney failure to be autonomous. However, for both of them, there are relevant issues that must be addressed before translation into clinical use and these are discussed in this review. PMID- 26905098 TI - Retrieval cue and delay interval influence the relationship between prospective memory and activities of daily living in older adults. AB - OBJECTIVE: Older adults commonly experience mild declines in everyday functioning and the strategic aspects of prospective memory (PM). This study used multiprocess theory to examine whether the strategic demands of retrieval cue type (event vs. time based) and delay interval length (2 vs. 15 min) influence the relationship between PM and activities of daily living (ADLs) in older adults. METHOD: Participants included 97 community-dwelling older adults recruited from the Western Australia Participant Pool. Participants were administered the Memory for Intentions Screening Test (MIST) and Prospective and Retrospective Memory Questionnaire (PRMQ) as part of a larger neurocognitive assessment. A knowledgeable informant completed the Activities of Daily Living Questionnaire (ADLQ), from which a cutpoint of >= 1 was used to classify participants into "ADL normal" (n = 37) or "mild ADL problems" (n = 60) groups. Repeated measures multivariate analysis of variance (MANOVA) controlling for age was conducted with ADL group as the between-subjects factor and either MIST or PRMQ cue and delay scores as the within-subjects factors. RESULTS: We observed a significant ADL group by PM interaction on the MIST, with pair-wise analyses showing that the mild ADL problems group performed worse than ADL normal participants on the 15-min time-based scale (p < .001, Cohen's d = 0.71). No other MIST or PRMQ cue-delay variable differed between the two ADL groups (ps > .10). CONCLUSION: Findings indicate that decrements in strategically demanding cue monitoring and detection over longer PM delays may partly explain older adults' mild problems in everyday functioning. Findings may inform neuropsychological interventions aimed at maintaining ADL independence and enhancing quality of life in older adults. PMID- 26905100 TI - Scar Functions, Barriers for Chemical Reactivity, and Vibrational Basis Sets. AB - The performance of a recently proposed method to efficiently calculate scar functions is analyzed in problems of chemical interest. An application to the computation of wave functions associated with barriers relevant for the LiNC ? LiCN isomerization reaction is presented as an illustration. These scar functions also constitute excellent elements for basis sets suitable for quantum calculation of vibrational energy levels. To illustrate their efficiency, a calculation of the LiNC/LiCN eigenfunctions is also presented. PMID- 26905101 TI - Regorafenib: A novel tyrosine kinase inhibitor: A brief review of its therapeutic potential in the treatment of metastatic colorectal carcinoma and advanced gastrointestinal stromal tumors. AB - Regorafenib is a novel oral multitargeted tyrosine kinase inhibitor having both antitumor and anti-angiogenic activities. Regorafenib was recently approved by US Food and Drug Administration in February 25, 2013 in the treatment for patients with advanced gastrointestinal stromal tumor and for the treatment of patients with metastatic colorectal carcinoma after disease progression or intolerance to imatinib mesylate and sunitinib therapy. Oral regorafenib demonstrates a high level of efficacy with acceptable tolerability with the 160 mg daily for 3 weeks followed by 1 week off schedule; a continuous schedule could be of interest. Hypertension, mucositis, hand foot skin reaction, diarrhea and asthenia are the most common side-effects. Regardless of these encouraging results, studies investigating, adjuvant and neoadjuvant settings are awaited, as well as trials using regorafenib in combination with chemotherapy or other targeted therapies. Clinical trials investigating regorafenib in other tumor types are ongoing. PMID- 26905103 TI - Single-walled and multi-walled carbon nanotubes based drug delivery system: Cancer therapy: A review. AB - Carbon nanotubes (CNTs) are advanced nano-carrier for delivery of drugs especially anti-cancer drugs. In the field of CNT-based drug delivery system, both single-walled carbon nanotubes (SWCNTs) and multi-walled nanotubes (MWCNTs) can be used for targeting anticancer drugs in tissues and organs, where the high therapeutic effect is necessary. Benefits of the carbon nanotubes (CNTs) in drug delivery systems are; avoiding solvent usage and reducing the side effects. Therefore, the present review article described about achievement of SWCNTs and MWCNTs to deliver the anticancer drugs with different cancerous cell lines. PMID- 26905102 TI - Primary chondrosarcoma in the young. PMID- 26905104 TI - Advanced prostate cancer presenting as bilateral testicular hydrocele. PMID- 26905105 TI - Dual surrogate markers for rapid prediction of epidermal growth factor receptor mutation status in advanced adenocarcinoma of the lung: A novel approach in resource-limited setting. AB - INTRODUCTION: Tyrosine kinase inhibitors have revolutionized the treatment of metastatic lung cancer in patients with epidermal growth factor receptor (EGFR) mutations. Amplified refractory mutation system (ARMS)-reverse transcription polymerase chain reaction (RT-PCR), the current standard for detecting EGFR mutation status is time-consuming and highly expensive. Consequently any surrogate test which are cheaper, faster and as accurate as the PCR method will help in early diagnosis and management of patients with lung cancer, especially in resource-limited settings. MATERIALS AND METHODS: Eighty-five patients, all of South Indian origin, with adenocarcinoma of lung, registered between October 2009 and January 2013, were evaluated for EGFR mutation status by using scorpion probe based ARMS RT-PCR method. Immunohistochemical (IHC) was performed using the phosphorylated AKT (P-AKT) and thyroid transcription factor-1 (TTF-1) on above patient's sample, and the results were compared with EGFR mutation tests. RESULTS: EGFR mutation was positive in 34 of 85 patients (40%). P-AKT and TTF-1 were positive in 50 (58.8%) and 68 (80%) patients respectively. Both P-AKT and TTF-1 had statistically significant correlation with EGFR mutation status. Positive and negative predictive value of P-AKT in diagnosing EGFR mutation was 58% and 85.5% and that for TTF-1 was 48.5% and 94.1%, respectively. The problem of low positive predictive value can partly be overcome by testing P-AKT and TTF 1 simultaneously. CONCLUSION: P-AKT and TTF-1 using IHC had statistically significant correlation with EGFR mutation with high negative predictive value. In the case of urgency of starting treatment, EGFR mutation testing may be avoided in those patients who are negative for these IHC markers and can be started on chemotherapy. PMID- 26905106 TI - Successful treatment of a dual malignancy. PMID- 26905107 TI - Conventional cytology, visual tests and evaluation of P16(INK4A) as a biomarker in cervical intraepithelial neoplasia. AB - OBJECTIVES: (1) To detect cervical intraepithelial neoplasia (CIN) using Papanicolaou test (PAP test), visual tests (visual inspection after the application of acetic acid [VIA], visual inspection after the application of Lugol's iodine [VILI]), colposcopy, and biopsy. (2) To study the biomarker p16(INK4A) expression by immunostaining. MATERIALS AND METHODS: Experimental study was conducted from November 2009 to April 2011. 1500 women were screened for cancer cervix using conventional PAP test, VIA, and VILI. Sensitivity, specificity, positive, and negative predictive values of these tests were calculated individually, sequentially, and in parallel. Women having positive results underwent colposcopy and biopsy if required. p16(INK4A) expression in biopsy samples was studied using immunohistochemistry. RESULTS: All test positive cases (n = 235) underwent colposcopy. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of PAP with atypical squamous cells of undetermined significance (ASCUS) as cut-off was 40%, 99.25%, 35.25%, and 99.39%; VIA was 60%, 93.06%, 8.03%, and 99.56% and VILI was 80%, 86.06%, 5.4%, and 99.76%, respectively. When PAP, VIA, and VILI were used in parallel sensitivity, specificity, PPV, and NPV improved to 100%, 85.18%, 6.38%, and 100%, respectively. Colposcopic abnormalities were detected in 83 and biopsy proven CIN in 15. p(16INK4A) expression was seen in eight of 15 CIN cases. CONCLUSIONS: (1) PAP test and visual techniques are complementary. (2) p(16INK4A) expression was seen in majority of CIN 2 lesions suggesting a higher grade lesion. PMID- 26905108 TI - A case of metastatic infiltrating ductal breast carcinoma with initial metastases to the optic nerve and subsequent extra ocular muscle involvement. PMID- 26905109 TI - Is there relationship between excision repair cross-complementation 1 expression level and response to treatment and prognosis in an advanced stage lung cancer treated with cisplatin-based chemotherapy? AB - AIM: It is important to know the tumor resistance against cisplatin before the treatment of non-small cell lung cancer (NSCLC). The purpose of this study was to evaluate the response to treatment and survival in patients with NSCLC treated with cisplatin-based chemotherapy according to excision repair cross complementation 1 (ERCC1) expression. MATERIALS AND METHODS: Among 119 patients treated with cisplatin and vinorelbine or docetaxel, 39 (32%) patients enrolled who have enough tumor tissue to analyze ERCC1 expression. ERCC1 expression defined as negative in score 0-1, positive in score 2-3. RESULTS: There was no difference between ERCC1 positive and negative groups (P = 0.63). Mean survival was 14.7 months (95% confidence interval [CI]; 10.0-19.3 month) in ERCC1 negative group, 10.9 months (95% CI; 7.4-14.3 month) in ERCC1 positive group (P = 0.23). Progression free survival was 7.9 months in ERCC1 negative group (95% CI; 5.8-9.9 months), 6.2 months in ERCC1 positive group (95% CI; 4.0-8.5 months) (P = 0.27). CONCLUSION: Identification of ERCC1 expression level of tumor tissues in NSCLC patients before treatment was not useful in prediction of treatment response and prognosis. PMID- 26905110 TI - Symptomatic Cytomegalovirus reactivation related to chemoradiotherapy for adenocarcinoma of lower third esophagus and gastro-esophageal junction cancer. PMID- 26905111 TI - A clinical study to assess the pathological involvement of occult supraclavicular lymphnode metastasis in case of locally advanced operable breast carcinoma. AB - PURPOSE: The prognosis of ipsilateral supraclavicular lymph node (SCLN) recurrence after early breast cancer appears to be worse than for other locoregional recurrences, but better than for distant metastases. Prophylactic radiotherapy (RT) to supraclavicular region decreases risk of ipsilateral SCLN recurrence. Currently, all patients with locally advanced breast cancer are considered high-risk for SCLN metastasis and treated with prophylactic RT. This study is carried out to identify risk factors associated with occult SCLN metastases in locally advanced breast cancer. MATERIALS AND METHODS: Total 48 female patients of all ages presenting with locally advanced carcinoma of breast who were operable by protocol criteria were included in the study. All the patients underwent modified radical mastectomy with supraclavicular lymphnode dissection. The resected specimen was processed for the histopathological analysis. RESULTS: Occult SCLN metastases are found in 25% (12/48) of the patients in this study. Eleven factors were identified and analyzed to know whether or not they are associated with SCLN metastasis. Of those only pathological N stage (7% for 2 weeks was required in only one (6.7%) patient. There were no toxicity-related drug discontinuations. Hypothyroidism (n = 4; 26.7%) and hand-foot syndrome (n = 3; 20%) were the most common toxicities. There were no complete and 4 (26.7%) partial responses while prolonged disease stability was seen in 8 (53.3%) patients. At a median follow-up of 81 months in surviving patients, the median progression-free and overall survivals were 15.5 and 18.7 months, respectively. CONCLUSIONS: Sunitinib appears to be an effective and well-tolerated treatment for Indian patients with imatinib resistant GIST with outcomes similar to that reported previously. Adverse effects can be reasonably well managed using a dose modification strategy. PMID- 26905127 TI - p-190 chronic myelogenous leukemia presenting as extramedullary blast crisis. PMID- 26905128 TI - Neglected orthopedic oncology--Causes, epidemiology and challenges for management in developing countries. AB - BACKGROUND: Management of malignant bone and soft tissue tumors remains an overwhelming confront to orthopedic surgeons. The challenge is discriminating in developing countries due to inadequate diagnostic and therapeutic amenities and unawareness. A lot has been discussed about the neglected orthopedic trauma, but the published literature on the causes and management of neglected bone and soft tissue tumors is sparse. Hence, current study was undertaken to highlight the causes of neglect and therapeutic challenges for managing these neglected tumors in developing countries. AIMS AND OBJECTIVES: To determine the causes of neglect of malignant bone and soft tissue tumors, their epidemiology (including their relative frequencies, age, gender discrimination, anatomical sites of occurrence and histological characteristics) and difficult aspect of management due to neglect or delayed presentation. MATERIALS AND METHODS: This was an appraisal of the neglected malignant bone and soft tissue tumors presented to J. N. Medical College and Hospital from June 2008 to May 2013. Criteria for labeling the tumor as neglected malignant bone and soft tissue tumor was delayed presentation (>3 months), locally advanced disease, ulceration, sepsis, fungating mass or metastasis at the time of presentation. All the cases were reviewed and analyzed for age, gender, histological types, educational status and socioeconomic status of the family, any prior treatment by traditional bone setters or registered medical practitioner, cause of delay for seeking medical advice. We have also analyzed the treatment given at our institute and the outcome of the tumor. OBSERVATIONS AND RESULTS: Eighteen patients fulfilled the criteria for neglected malignant bone and soft tissue tumors, hence were included in study. Eight cases were of osteosarcoma, five cases were of Ewing's sarcoma, three cases were of chondrosarcoma and 1 case each was of pleomorphic liposarcoma and primary lymphoma of bone. According to Enneking staging system 11 cases were of stage III (distant metastasis) and 7 were stage II-B. Seven were females, and 11 were males. Age range was 5-68 years. 15 patients (83.3%) belonged to low socioeconomic status with 17 patients (94.4%) belonged to uneducated background. Cause of delay in seeking medical advice was neglect by the patient and family due to financial constraints, cultural and religious believes, lack of access to health care facilities, consultation with traditional bone setters and even misdiagnosis by qualified orthopedic surgeons. The tumors included were all unresectable and of huge sizes, hence were managed with amputation/dis articulation, chemotherapy or radiation. CONCLUSION: The current study tries to highlight the causes and quantity of neglect of malignant bone and soft tissue tumors prevalent in our country, which poses a therapeutic challenge for management and consequent mutilating surgeries with poor outcome resulting in loss of extremity and existence. PMID- 26905129 TI - Isolated Richter's transformation of brain parenchyma: Remission with DeAngelis protocol. PMID- 26905130 TI - Histological diversity and clinical characteristics of Ewing sarcoma family of tumors in children: A series from a tertiary care center in South India. AB - BACKGROUND: The Ewing sarcoma family of tumors (ESFT) are aggressive malignant tumors with small round cell morphology affecting mainly children and adolescents. The aim of this study is to classify the histological diversity and clinical characteristics of ESFT in children from a Tertiary Care Center in South India. MATERIALS AND METHODS: This retrospective descriptive study includes 51 cases of ES in children aged below 15 years. Clinical details were collected from case files. Histomorphological features were reviewed and tumors were subtyped into classic, primitive neuroectodermal tumor (PNET) and atypical variants along with immunohistochemical markers, cytogenetics, and fluorescence in situ hybridization (FISH). RESULTS: Fifty-three percent were female and 47% were male with mean age of 10 years. The most common site of involvement was skeletal involvement in 71%, followed by soft tissue involvement in 23%, and visceral involvement in 6%. Localized disease at presentation was seen in 44%, locally advanced disease in 28%, and metastatic disease in 28%. Recurrence was documented during follow-up in 18% of the cases. Histomorphologically, classic type was the most common (72%) followed by PNET (20%) category and atypical variant (8%). All cases were immunoreactive for CD99. Cytogenetic study in 12 cases showed translocation t(11;22) (q24;12) in 80% and variant translocations such as t(3;16), t(3;11) with nonspecific numerical abnormalities in 20%. FISH was carried out for documentation of four cases with atypical histomorphology. CONCLUSION: ESFT had wide histological variation which required confirmation by ancillary studies. PMID- 26905131 TI - Squamous cell carcinoma arising in an epidermal cyst. PMID- 26905132 TI - Analyzing multiple risk factors in patients with sarcomas. A case-control study. AB - CONTEXT: Sarcomas are a rare group of malignancies. Very little is known about their risk factors. AIMS: The aim was to evaluate different risk factors in patients with sarcomas and to determine the median age at diagnosis, differences in race, gender, histological grades and staging in sarcoma patients. SETTINGS AND DESIGN: A retrospective case-control study was conducted in a tertiary care hospital in the USA. This included patients diagnosed with sarcomas from year 2000 to 2010. MATERIALS AND METHODS: Data were extracted with the help of electronic medical records using International Classification of Diseases, Ninth revision codes. Healthy, matched controls were randomly selected from the same tertiary care hospital database. STATISTICAL ANALYSIS: Univariate comparisons between cases and controls were done using a two-group independent t-test for age and using Chi-square tests for the categorical variables. In order to identify possible independent predictors of sarcomas, a multiple logistic regression model was constructed using sarcoma status as the dependent variable and using, initially, all variables with a univariate P < 0.2 as independent variables. Variables were reduced in a manual stepwise manner to arrive at a final model. Statistical significance was set at P < 0.05. All analyses were performed using SAS 9.4 (SAS Institute Inc., Cary, NC, USA). RESULTS: A total of 425 sarcoma patients and 429 age, sex and race matched healthy controls were analyzed in this study. We found that a history of smoking and alcoholism was significantly associated with sarcomas. We also found that the history of cancer in first degree relatives had a significant relationship. In addition, patients with sarcomas are more likely to have a history of another malignancy when compared with controls. CONCLUSIONS: Smoking and alcohol are potential risk factors for sarcomas. In addition, a history of cancer in the first-degree relative is also a potential risk factor. Patients with sarcomas are likely to have a history of another malignancy when compared with controls. PMID- 26905133 TI - Epidemiology, diagnosis, surgical treatment and prognosis of the pancreatic neuroendocrine tumors: Report of 125 patients from one single center. AB - OBJECTIVE: The objective of the following study is to summarize the epidemiology of pancreatic neuroendocrine tumors (p-NETs) in our single institution, analyze the diagnostic characteristics, share the experience of surgical treatments and discuss the prognostic factors. METHODS: A retrospective collection and analysis of clinical data of 125 patients with p-NETs which were pathologically confirmed in our hospital from January 2002 to December 2012. RESULTS: A total of 125 patients of which 52 were males and 73 were females. Totally 92 patients had functional p-NETs, while non-functional p-NETs were diagnosed in 33 patients. The most common operative procedures performed were local resection of pancreatic tumor (47.2%), followed by distal pancreatectomy (29.6%). Thirty patients (28%) had post-operative complications, the most common of which was pancreatic fistula (22.4%). The overall survival rate at 5 years was 68.4%. The 5-year survival rate for patients with functional tumors was 75.1%, compared with 50.0% for those with non-functional tumors (P = 0.021). The survival time of patients with R0 resection was statistically longer than that of patients with Not R0 resection (P < 0.005). In univariate analysis, the most powerful predictors of poor outcome were gender, age, tumor size, functional status, surgical margins, lymph node invasion and distant metastasis. However only surgical margin and distant metastasis were significant predictors in multivariate analysis (P = 0.001, 0.047, respectively). CONCLUSION: p-NETs are an uncommon and heterogeneous group of tumors, with a rising incidence. Surgery is the most effective treatment. Surgical margin and distant metastasis were the most significant prognostic factors. Radical resection should be taken more into considerations. PMID- 26905134 TI - Spindle cell hemangioma of thyroid. PMID- 26905135 TI - Evaluation of biologic potential and risk stratification for predicting disease free survival after resection of primary gastrointestinal stromal tumor: A multivariate clinicopathological study. AB - BACKGROUND AND OBJECTIVES: Gastrointestinal stromal tumor (GIST) is mesenchymal neoplasms of the gastrointestinal tract, which express CD117, a c-kit proto oncogene protein and show gain of function mutation of c-kit gene. Apart from the presence of metastasis, the criteria to differentiate benign and malignant GISTs are not well-defined. Although a variety of prognostic factors have been investigated, no method has yet proven sufficient to enable reliable determination of malignancy in all cases. This study was planned to risk stratify the GIST cases with respect to the various clinicopathological features and to identify prognostic factors in GIST. MATERIALS AND METHODS: n histological and immunohistochemical analysis, 121 cases of GIST were identified. MIB-1 (Ki-67) labeling index (LI) was performed in 60 cases. Follow-up data was available for 93 patients. A P < 0.05 was taken as significant. RESULTS: Larger tumor size, high mitotic activity and Ki-67 LI of >10% were identified as significant predictors of disease-free survival in univariate analysis (P < 0.0001). Other factors of statistically significant value were a high cellularity (P < 0.0027), nuclear pleomorphism (P = 0.0002), epithelioid cell type (P = 0.0098), presence of tumor necrosis (P < 0.01), presence of skeinoid fibers (P = 0.042), S-100 negativity (P = 0.025). Extra-gastrointestinal GIST and metastasis were more frequently associated with progressive disease (PD) as compared with GIST (P < 0.0004), (P < 0.0001). On multivariate analysis size (P = 0.0025), Ki-67 labeling index (P = 0.0186) and mitotic count (P = 0.0375) emerged as independent prognostic predictors of PD. CONCLUSION: This study suggests that GIST in Asian population may have a different phenotype with some predilection to nodal metastasis. Of all the features studied, tumor size and mitotic index are the best prognosticators in GIST with the addition of Ki-67 LI, wherever available. PMID- 26905136 TI - Granulomatous mastitis and angiosarcoma of the breast masquerading as non-mass enhancement. PMID- 26905137 TI - Everolimus plus octreotide long-acting repeatable in advanced neuroendocrine tumors in the routine tertiary cancer care setting: An Indian experience. AB - BACKGROUND: Neuroendocrine tumors (NETs) are rare, heterogeneous, indolent tumors that are relatively insensitive to systemic chemotherapy. Therapeutic strategies for NETs broadly include somatostatin analogs, antiangiogenic therapy, and most recently, mammalian target of rapamycin inhibition. Combination therapy has shown promising antitumor activity and good tolerability in the randomized phase III trials. AIM: The aim was to evaluate the safety and efficacy of Everolimus plus Octreotide long-acting repeatable (LAR) in patients with advanced NETs in the routine tertiary cancer care setting in India in this postapproval, noninterventional trial. PATIENTS AND METHODS: Patients presenting to selected centers between 2011 and 2013 with histologically confirmed low-, intermediate- or high-grade advanced NETs who may have had prior exposure to cytotoxic chemotherapy (<=2 lines) were treated with oral Everolimus (10 mg/day) plus intramuscular Octreotide LAR (30 mg once every 28 days) until disease progression or unacceptable toxicity was seen. Patients were evaluated every 3 months for a response to therapy as per Response Evaluation Criteria in Solid Tumors. RESULTS: Everolimus plus Octreotide LAR was associated with a clinical benefit rate of 69% (best evaluable responses: Stable disease [SD] in 10 patients [63%], partial response in 1 patient [6%]). The average duration of therapy was 4.8 cycles, and 3 (17%) patients continued therapy for >=12 cycles (all achieved SD). The therapy was found to be well-tolerated in all patients. CONCLUSIONS: Everolimus plus Octreotide LAR appears to be safe and efficacious in patients with advanced NETs who may have had prior exposure to chemotherapy - a finding consistent with recently conducted major trials. PMID- 26905138 TI - Brain metastasis from carcinoma base of tongue after 9 years of disease free survival. PMID- 26905139 TI - Oxaliplatin induced acute tubular necrosis. PMID- 26905140 TI - Cystosarcoma phyllodes: Pathological enigma: A retrospective review of 162 cases. AB - PURPOSE: Phyllodes tumor (PT) is a rare fibroepithelial neoplasm comprising <1% of all breast tumors. Clinical spectrum ranges from benign (B), borderline (BL), and locally recurrent to malignant (M) and metastatic type. The aim of our study was to analyze the clinicopathological factors, compare treatment options, and evaluate outcome in patients with PT. METHODS: We retrospectively reviewed 162 women with PT. The surgical intervention varied from simple excision (lumpectomy)/wide local excision (WLE) in benign cases to simple/modified radical or radical mastectomy (SM/MRM/RM) in malignant and recurrent tumors. RESULTS: Out of 162 patients, B, BL, and M were 95 (58.64%), 29 (18%), and 38 (23.45%), respectively. Mean age, duration of lump, and size were 38 +/- 8 years, 28 +/- 10 months, and 12 +/- 5 cm, respectively. Recurrence rate with B, BL, and M was 15.78%, 41.37%, and 55.26%, respectively (P = 0.00001). As compared to WLE (22%), SM (23.8%), and MRM/RM (14.2%), recurrence was higher with lumpectomy (48.9%) (P = 0.004). Positive correlation was found between recurrence rate with the size of tumor (P = 0.008) and also number of recurrence with holoprosencephaly (P = 0.047). There was no association between the number of recurrences and size of tumor (P = 0.63). Malignant PT was seen in 38 (24%) and distant metastasis was seen in 7 (18%). Mean duration of follow-up was 42 months. CONCLUSION: WLE with negative margins should be the initial surgery for PT. The role of adjuvant radiotherapy and chemotherapy is uncertain. PT is pathological enigma. Till date, no factors can accurately predict the recurrence and outcome. PT is known for unpredictable behavior and high recurrence rates, hence long-term follow-up is advised. PMID- 26905141 TI - Chemotherapy for obstructive atelectasis in nonsmall cell lung cancer: Is this a treatment option? PMID- 26905142 TI - Use of colposcopy for diagnosing oral mucosal lesions: An illusion or a realistic possibility? AB - As oral physicians, we come across many oral mucosal lesions that usually require a supplementary biopsy with histopathologic examination to establish a definite diagnosis. The selection of the site for biopsy is the most important criteria to arrive at a correct diagnosis. As biopsy site is a subjective choice, it is possible that the biopsy specimens are taken from unrepresentative areas of the lesion. At present, though there are simple chair side methods to aid the diagnosis of such changes, there is a high risk of false positives. Hence, there is a need of a simple and reliable method for selecting the most appropriate area for biopsy. One such method is colposcopy that may be beneficial as compared to routine clinical examination. Hence, this article stresses on the colposcopic method that can be used to select biopsy sites which should be evaluated in further clinical studies. PMID- 26905143 TI - Leiomyosarcoma of penis. PMID- 26905144 TI - Evaluation of stapled closure following laryngectomy for carcinoma larynx in an Indian tertiary cancer centre. AB - BACKGROUND AND AIM: Stapling devices are used for pharyngeal closure after laryngectomy for the past few decades although it has not gained wide acceptance. This study is aimed at evaluating the role of stapler in pharyngeal closure after laryngectomy. METHODS: Thirty consecutive patients who underwent stapled laryngectomy at our institution from October 2004 to February 2008 were evaluated retrospectively. Linear stapler (Proximate TX 60; Ethicon Inc.) was used for closure of neopharynx. RESULTS: There were 28 males and 2 females with mean age of 54.5 years (54.5 +/- 11.2). Nineteen of these patients (63.3%) had salvage laryngectomy and two patients (6.7%) had laryngectomy for a second primary tumor. Twenty-eight patients had total laryngectomy (TL), whereas two had extended TL. Eight patients had salivary leak (26.7%). Of these, 6 (75%) had prior radiation. All salivary leaks except one were managed conservatively. Follow-up ranged from 7 to 54 months (median: 21 months). Seven patients (23.3%) developed recurrence, six at the stoma, of which 5 (83.3%) had initial extension of disease to the subglottis. Four-year disease-free survival was 54.4%. CONCLUSION: Pharyngeal closure by linear stapler is an efficient and safe method of fashioning the neopharynx after laryngectomy with no added risk of occurrence of pharyngocutaneous fistula in primary and salvage laryngectomies. PMID- 26905145 TI - Intra-abdominal cystic lymphangioma in an adult female masquerading ovarian tumor. PMID- 26905146 TI - Pre-surgical road map for thyroid cancer and large goiters: Practical benefits of detailed radiological evaluation by surgeon. AB - INTRODUCTION: Pre-surgical radiological evaluation of neck is often mandatory for surgical planning in high risk thyroid cancer and large goiters. Frequently, surgeons are overdependent on radiologist's report. In this context, we analysed the practical benefits of surgeon's independent radiological evaluation in our institutional experience. MATERIAL AND METHODS: This prospective study was conducted in Endocrine Surgery department of a teaching hospital in South India. Cases operated between January 2011 and June 2012 (18 months) were included. Films of cross-sectional imaging were read in detail by primary and assistant surgeons in correlation with stepwise operative planning and documented. Cases with additional radiological signs on surgeon's evaluation, which were missing in radiologist's report are discussed in detail. RESULTS: F: M ratio is 67:24. Mean age was 45.3 +/- 9.8 years (37 - 76). Forty-seven cases of thyroid cancer and 44 cases of large goiters were analysed. Surgeon read additional signs such as obliterated fat plane between goiter and subcutaneous plane; level I lymph nodes; bilateral cervical lymphadenopathy, internal jugular vein thrombus, and pharyngeal invasion helped in pre-operatively planned modification of operative steps for optimal R0 resection and total thyroidectomy. A mean of 1.42 +/- 0.83 (1 - 6), additional signs were detected on surgeon's radiological evaluation compared to radiologist's report in 41.7% of cases. These findings modified the pre-operative plan, facilitating better surgical outcome in 28.6% of cases. CONCLUSION: In high-risk thyroid cancer and large goiters, detailed radiological evaluation by surgeon facilitates optimal surgical resection and superior outcome compared to radiologist report-guided surgery. PMID- 26905147 TI - Head and neck cancer in geriatric patients: Analysis of the pattern of care given at a tertiary cancer care center. AB - BACKGROUND AND AIM: The percentage of elderly people with head and neck cancers (HNC) is on the rise. This makes HNC in this group of patients an important issue for healthcare providers. The present study was planned to analyze the patterns of care given to the geriatric patients and to identify the factors influencing the decision making process. MATERIALS AND METHODS: Data of all the elderly patients (>=65 years) registered in the year 2012, with histologically proven HNC (all sites, stages, histopathological types, except lymphoma, sarcoma and cervical metastasis of unknown origin) receiving treatment (definitive/palliative) were collected. RESULTS: A total of 270 patients were included in this study. The median age was 72 years (range: 65-101), with predominant male population (70%, n = 190). Oral cavity squamous cell carcinoma (SCC) was the most common cancer (57%, n = 154). Eastern Co-Operative Oncology Group performance status (PS) of 0-2 was seen in 91% of the patients. Co morbidities were present in 139 (51.5%) patients. 50% (n = 134) of the patients received palliative intent treatment, 45% (n = 123) definitive treatment, whereas in 5% (n = 13) the intent was not mentioned. Age, a clinical stage and PS significantly influenced the decision making on the intent of treatment. 208 (77%) patients completed their treatment irrespective of the intent. Age was the only factor influencing treatment completion irrespective of the intent. CONCLUSION: Geriatric HNC patients frequently present with advanced disease, having multiple co-morbidities. Hence, a multidisciplinary team management of these patients is essential, also taking into account of the social and financial support available to these patients. PMID- 26905148 TI - Nasopharyngeal cancers: A retrospective comparative analysis of radiotherapy alone versus chemo-radiation (Benghazi experience). AB - INTRODUCTION: Cancer of Nasopharynx is an important disease in Maghreb region. 75 patients (4.3%) of cancer nasopharynx between the years 1995 to 2000 were referred to our centre in Benghazi out of total 1757 patients. This study was done to analyze the clinical presentations and to study response to the treatment practiced. MATERIALS AND METHODS: 59 patients were available with full records excluding the recurrent and metastatic presentation. 37 were males with 22 females (1.7:1), (31/59) 52% patients were from 25-49 years, (17/59) 28.8% were from 50-60 years. 44/59 (74%) patients presented with Lymphadenopathy either unilateral or bilateral. 46/59 (78%) of patients were in clinical stage II or III. 44/59 (74%) of patients were of undifferentiated histology. RESULTS: The pattern of clinical response and trend of follow up those that received neoadjuvant chemotherapy and radiotherapy and radiotherapy alone are discussed. DISCUSSION: In our analysis, we also found that the patients who had received chemotherapy by and large had a less trend to towards developing metastatic disease and local recurrence and faired better. CONCLUSION: We are now following the protocol of Neoadjuvant chemotherapy followed by chemo-radiotherapy and followed by chemotherapy and results will mature in the years to come. PMID- 26905149 TI - Prolonged survival of a patient with inoperable, locally advanced adenocarcinoma of pancreas after autologous immune enhancement therapy with chemotherapy. PMID- 26905150 TI - Solitary fibrous tumor of orbit: A rare entity. PMID- 26905152 TI - An unusual case of squamous cell carcinoma of buccal mucosa with distant metastases. PMID- 26905151 TI - Evaluation of salivary function by sialoscintigraphy in locally advanced nasopharyngeal cancer patients after intensity modulated radiotherapy. AB - PURPOSE: This study aimed to evaluate the salivary gland function changes by sialoscintigraphy in locally advanced nasopharyngeal cancer (NPC) after intensity modulated radiotherapy (IMRT). MATERIALS AND METHODS: Salivary function was assessed by sialoscintigraphy. Quantitative sialoscintigraphy was performed in 24 NPC patients prior to and after IMRT. Results were categorized in four groups according to the duration of treatment. The sialoscintigraphy parameters were examined. RESULTS: Sialoscintigraphy showed a significant difference in the secretion of each interval groups. The parameters of scintigraphy, except maximum accumulation (MA) of submandibular glands, decreased first after radiotherapy, and then recovered. However, the MA of submandibular glands was continuously downhill after radiation. CONCLUSIONS: The sialoscintigraphy parameters of each gland changed with the different radiation dose and follow-up intervals. The salivary function was influenced after radiotherapy in locally advanced NPC, especially, in the submandibular gland. Strategies to improve the salivary function should be assessed. PMID- 26905154 TI - Rehabilitative management of segmental mandibulectomy patient. PMID- 26905153 TI - Predictivity of human papillomavirus positivity in advanced oral cancer. AB - BACKGROUND AND OBJECTIVE: Human papillomavirus (HPV) is a known prognostic factor world over in patients of carcinoma oropharynx. The role of HPV in oral cancers has not been investigated adequately. We tried to identify standard clinicopathological features in oral cancer, which would predict HPV-positivity. METHODS: This was a retrospective analysis of 124 cases of T4 oral cancer patients at our center. HPV-positive was defined in accordance with positive p16 immunohistochemistry done on pretreatment local tumor site biopsy. Age, sex, habits (smoking history and oral tobacco), Eastern Cooperative Oncology Group performance status (ECOG PS), T stage, N stage, grade, and site were selected, for testing of prediction for HPV-positivity. The analysis was performed by R studio version 3.1.1. Two-sample test for equality of proportions with continuity correction was used to identify factors predicting for HPV-positivity. P = 0.05 was considered as significant. RESULTS: Of 124 patients, 16 patients (12.9%) were HPV-positive. The median age of the whole cohort was 43 years (interquartile range 37-52 years) with 15 females (12.1%). All had squamous cell carcinoma (100%). The grade of the tumor was well differentiated in 9 patients (7.2%), moderately differentiated in 98 patients (79.1%), and poorly differentiated in 17 patients (13.7%). The ECOG PS 0 in 19 patients (15.3%), 1 in 104 patients (83.9%), and 2 in 1 patient (0.8%). The subsite of the tumor was buccal mucosa in 74 patients (59.7%), anterior two-third of tongue in 33 patients (26.6%), and others in 17 patients (13.7%). None of the tested factors except the use of oral tobacco were statistically significantly associated with HPV-positivity. History of tobacco usage had a statistical trend toward ability to predict HPV positivity. The proportion of patients with HPV-positive oral cancer in patients without history usage of oral tobacco was 31.3% while it was 10.2% in patients with previous history of tobacco use (P = 0.03). CONCLUSION: Standard clinicopathological variables could not predict for HPV-positivity. Negative history of tobacco (smokeless) usage showed statistical trends toward ability to predict HPV-positivity in oral cancer patients. PMID- 26905155 TI - Stromal characterization and comparison of odontogenic cysts and odontogenic tumors using picrosirius red stain and polarizing microscopy: A retrospective and histochemical study. AB - INTRODUCTION: Odontogenic lesions represent a range of conditions, the features of which probably depend on the stage of induction towards tooth formation reached prior to neoplastic or hamartomatous proliferation. It has been also suggested that inductive changes may allow progression from one type of odontogenic tumor to another. The epithelium also plays an important role in the pathogenesis of these lesions; even stroma is likely to play an equally important role in the pathogenesis and biological behavior. So, this study was performed to investigate, compare, and correlate different types of collagen fibers in odontogenic cysts and odontogenic tumors. MATERIALS AND METHODS: Thirty each pre diagnosed odontogenic cysts and tumors were histochemically analyzed using a special stain (Picrosirius red stain) and polarizing microscopy. RESULTS: Seven cases (99%) of inflammatory cysts exhibited predominantly greenish-yellow birefringence indicating procollagen, intermediate, or pathologic collagen fibers suggestive of loosely packed collagen fibers. Predominant yellowish-orange birefringence exhibited by 21 cases (99%) of developmental cysts was comparable to the yellowish-orange and orangish-red to red birefringence exhibited by odontogenic tumors suggesting tightly packed fibers. CONCLUSIONS: The Picrosirius red stain in conjunction with polarizing microscopy serves as a specific and sensitive tool in characterizing collagen fibers in odontogenic cysts and odontogenic tumor. PMID- 26905156 TI - Neoadjuvant chemotherapy and surgery versus surgery alone in resectable esophageal cancer. AB - The aim of this article is to review randomized and non-randomized trials and meta-analysis comparing neoadjuvant chemotherapy (NAC) plus surgery versus surgery alone in resectable esophageal cancers. The article examines the value of NAC as a standard of care in the era of multimodality treatment with availability of different therapeutic options. The emphasis is on assessment of benefit of NAC in terms of survival (long and short term) rate of RO resection in resectable esophageal cancers of any histopathologic type. The in-hospital post-operative morbidity and mortality in NAC group, chemotherapeutic drug regimens and their response rates and optimal number of cycles to be used will also be addressed. PMID- 26905157 TI - Lymph node metastasis: A bearing on prognosis in squamous cell carcinoma. AB - Nodal status is a significant predictor for survival of patients with oral squamous cell carcinoma (SCC), sentinel lymph node (SLN) biopsy, step sectioning of SLNs, and immunohistochemistry have changed the detection of tumor deposits in lymph nodes (LNs). The extent of LN metastasis is a major determinant for the staging and the prognosis of most human malignancies and often guides therapeutic decisions. Metastasis to regional lymph node (RLN) is a complex process. It is often associated with several clinical and pathological characteristics. The involvement of RLN is often, a harbinger for increased risk of metastasis. New knowledge in this area can enable the clinicians and pathologists to study and treat tumors in a more directed fashion. A molecular approach to factors that predicts the likelihood of RLN metastasis could eliminate the reoccurrence of the tumor in the form of "micrometastasis" and "skip" metastasis. The aim of this review is to discuss different modes of spread of metastasis in SCC. PMID- 26905158 TI - Neuropathic pain in cancer patients: A brief review. AB - Neuropathic pain (NP) is initiated or caused by a primary lesion or dysfunction in the nervous system. The NP in cancer patients is typically due to a combination of inflammatory, neuropathic, ischemic, infiltrative, and compression mechanisms that involve one or more anatomic sites. These patients will often have various types of co-existing pain syndromes and co-morbidities. Thus, any treatment plan needs to be individualized. After a thorough clinical assessment and evaluation, a combination therapy including anticonvulsants, antidepressants, N-methyl-D-aspartate antagonists, opiates, topical agents, and interventional procedures should be considered in these patients. PMID- 26905159 TI - A rare case of extramedullary plasmacytoma arising from posterior mediastinum. PMID- 26905160 TI - Gallbladder cancer incidence in Gwalior district of India: Five-year trend based on the registry of a regional cancer center. AB - BACKGROUND: We have reported here the 5-year incidence (2004-2008) of gallbladder cancer (GBC) in North Central India along with its descriptive epidemiology. This provides potential clues for better prevention. The present study has also evaluated the association of ABO blood groups with GBC. PATIENTS AND METHODS: The study comprised 742 GBC cases referred to the regional cancer hospital, Gwalior, during 2004-2008. The demographic statistics of Gwalior district was considered to calculate the relative risk and incidence rates. ABO blood group distribution amongst 90,000 healthy subjects registered in the local blood bank during 2002 2007 was taken as controls to study the association of blood groups with GBC. RESULTS: The age-standardized total incidence rate of GBC was calculated to be 7.16/1,00,000. The relative risk of females getting GBC was 2.693 at 95% confidence interval of 2.304-3.151 (P < 0.0001). The females formed 69.5% of total cancer cases, with age-standardized incidence rate of 10/1,00,000. The mean age of male and female GBC cases was found to be 55.4 years (SD = 13, SE = 0.77) and 51.5 years (SD = 12.3, SE = 0.50), respectively. The blood groups A (P = 0.0022) and AB (P < 0.0001) had a positive association with GBC with significant level of differences in comparison to controls. CONCLUSION: Our study provided an estimate of a 5-year incidence of GBC in North Central India for the first time. With regard to the association of risk factors like obesity, age, and urban living with GBC, the findings of the present study are contradictory to the general opinion. Blood groups A and AB were found to be associated with GBC, which would be provisional for further investigations. PMID- 26905161 TI - 18F-FDG positron emission tomography scan findings in a case of rituximab-CHOP induced pneumonitis. PMID- 26905162 TI - Solid pseudopapillary tumor of the pancreas: A retrospective analysis of 36 cases from a single institution in India. AB - BACKGROUND: Solid pseudopapillary tumor (SPT) of the pancreas is uncommon, occurring predominantly in young women. We analyzed the clinicopathological features of SPT diagnosed in our institution. MATERIALS AND METHODS: A retrospective analysis of all cases of SPT diagnosed in the Department of Pathology from January 2001 to September 2012, utilizing an electronic database search, was carried out. In all, 36 cases (35 resections and 1 fine needle aspiration cytology with cell block material) were found. All these cases were then analyzed for clinical presentation, duration and histopathological features, including immunohistochemistry and correlated with the clinical outcome. RESULTS: The mean age of patients (31 females) was 24.1 years. The SPT was suspected preoperatively in 25% of cases. Tumor location was equally common in head (15), body (9), tail (8), distal body and tail (3), and neck (1). Thirty five patients underwent resection. The mean tumor size was 7.16 cm. Grossly, the tumors were solid and cystic (22), predominantly solid (11) or entirely cystic (2). Histologically, pseudopapillary structures, cholesterol clefts, hemorrhage, necrosis, and foam cells were commonly seen. Infiltration into the adjacent pancreas or capsule and perineural invasion were seen in some cases. Immunostaining for CD 10, CD56, and vimentin were positive. Chromogranin and cytokeratin were negative. Follow up in 20 patients from 2-82 months did not show evidence of recurrence or metastasis, even in those with limited surgery or minimal parenchymal or focal perineural infiltration. CONCLUSION: This study suggests that a management approach with only limited complete tumor resection would be adequate in these tumors. PMID- 26905163 TI - Increased survival of patients with end-stage hepatocellular carcinoma due to intake of ONCOXIN(r), a dietary supplement. AB - BACKGROUND AND AIMS: Treatment and management of patients with end-stage hepatocellular carcinoma (HCC) represents a formidable challenge to contemporary branches of medical sciences. The study presented here was conducted to assess the utility of nutrient supplement, if any, for management of patients with end stage HCC. MATERIALS AND METHODS: A total of 19 patients with end-stage HCC (Barcelona Clinic Liver Cancer [BCLC] staging D) were provided with ONCOXIN(r) for 3 months. Another 10 patients with end-stage HCC (BCLC stage D) with similar clinical conditions received conservative management, but they did not give consent for taking ONCOXIN(r) (non-ONCOXIN(r) group). All patients of both groups were followed on regular basis until their death. STATISTICAL ANALYSIS: The results were expressed as mean and standard deviation. Comparison between groups was performed using Student's t-test or the Mann-Whitney U test. For categorical data, Chi-square or Fisher exact test was applied. RESULTS: All patients of the control group (non-ONCOXIN(r) group) (10 of 10 patients) died within 2 months after study commencement. On the other hand, 10 of 19 patients receiving ONCOXIN(r) died within 2 months (less than 53% patients) after the start of taking ONCOXIN(r) (P < 0.05, compared with patients of non-ONCOXIN(r) group). Five more patients died within 5 months after the start of intake of ONCOXIN(r). Four patients receiving ONCOXIN(r) survived for more than 6 months after study commencement. CONCLUSIONS: Although this is a preliminary report, it inspires considerable optimism about safety and efficacy of a food supplement for management of patients with end-stage HCC. PMID- 26905165 TI - Aggressive primary malignant myoepithelioma of the maxillary sinus. PMID- 26905164 TI - Metastatic malignant melanoma in a young adult with unknown primary. PMID- 26905166 TI - Treatment of patients with metastatic pancreatic cancer: Experience from a tertiary Indian cancer center. AB - BACKGROUND: The aim of this study was to look at the outcome of patients with metastatic pancreatic cancer treated at a tertiary cancer center in India. PATIENTS AND METHODS: A total of 101 patients with locally advanced and metastatic pancreatic cancer diagnosed between May 2012 and July 2013 were identified from a prospectively maintained database at the tertiary cancer center. Overall survival (OS) was computed using the Kaplan-Meir product limit method and compared across groups using the log-rank statistics. Cox proportional hazards model, adjusted for a number of patient and tumor characteristics, was then used to determine factors prognostic for OS. RESULTS: Median age at diagnosis was 55 years (range: 21-81 years). 57.4% (n = 58) of patients were male, 22% (n = 22) had performance status (PS) of <2 at diagnosis and 89% received first-line chemotherapy, while the rest received best supportive care. For the whole cohort, 6 month and 1-year OS was 57% (95% confidence interval [CI]: 46-66%) and 47% (95% CI: 35-57%), respectively. In a multivariable model, PS <2 and oligometastatic disease were associated with a significantly decreased risk of death. CONCLUSION: Results from our analysis indicate that the prognostic outcome among Indian patients with metastatic pancreatic cancer is poor with survival outcomes similar to those reported in North America and Europe. PMID- 26905167 TI - Infantile myofibromatosis of uterus: A case report. PMID- 26905168 TI - Treatment-associated severe thrombocytopenia affects survival rate in esophageal cancer patients undergoing concurrent chemoradiotherapy. AB - BACKGROUND: Esophageal cancer is commonly treated with surgery, concurrent chemoradiotherapy (CCRT), or a combination of both. The correlation between the hematological parameters during CCRT and early survival of esophageal cancer has not been fully evaluated. MATERIALS AND METHODS: We analyzed the records of 65 esophageal cancer patients treated by CCRT between 2007 and 2010 retrospectively. The association between CCRT-associated myelosuppression, demographic variables, and survival rates were analyzed by univariate and multivariate analysis. RESULTS: The univariate analysis showed that tumor extent of T3-4, a higher stage of tumor, a lower albumin level, grade 3 or higher anemia and thrombocytopenia, and interruptions in treatment affected survival rates. Further, the multivariate analysis revealed that stage IV (P = 0.030) is an independently negative prognostic factor for a one-year survival rate. Stage IV (P = 0.035), tumor extent of T3-4 (P = 0.002), and grade 3-4 thrombocytopenia (P = 0.015) are independently negative prognostic factors for a two-year survival rate. CONCLUSIONS: Severe decrease in platelet count during CCRT independently affects survival of esophageal cancer patients in addition to stage of the tumor. PMID- 26905169 TI - Population pharmacokinetic analysis to identify the possibility of interaction between anti-cancer agents. AB - BACKGROUND: A number of molecularly targeted agents in oncology are tested in clinical studies in combination with conventional chemotherapy and/or radiotherapy. There is the possibility that the pharmacokinetics and dynamics of these targeted agents may be different when administered alone as against when administered in combination with other agents. AIM: The aim of this study is to understand the effects of addition of combination agents on the pharmacokinetics of a new, investigational, cyclin dependent kinase inhibitor anti-cancer drug (Compound A) using population pharmacokinetic (pop-PK) analysis. MATERIALS AND METHODS: Integrated pop-PK analysis of data obtained from multiple phase I/II studies of Compound A, given alone or in combination with other agents. RESULTS: A two compartmental model was found suitable to explain the pharmacokinetics of Compound A. No statistically significant influence of patient covariates or combination agents on the pharmacokinetic parameters of the central compartment was detected up to a significance level of 0.01. Model evaluation showed that the parameter estimates are stable and that the variability in the data was well reproduced by the model. CONCLUSIONS: This study represents the first time that a pop-PK analysis was performed in India for a targeted anti-cancer agent being developed in India. Such an analysis is useful to not only understand the influence of patient covariates and combination agents on the pharmacokinetics of a new investigational agent, but would also be valuable in the simulation of later phase clinical trials for the agent under development. PMID- 26905170 TI - Secondary pancreatic involvement by precursor T-cell acute lymphoblastic leukemia presenting as acute pancreatitis. PMID- 26905171 TI - Spontaneous adverse drug reaction monitoring in oncology: Our experience. AB - BACKGROUND: Adverse drug reaction (ADR) monitoring is slowly developing as an important aspect of healthcare. The aim of the study was to study the pattern of adverse drug reactions in the Oncology department of a tertiary care hospital. MATERIALS AND METHODS: This was a prospective study conducted in the Oncology department of a tertiary care hospital in which ADRs were reported spontaneously. The ADRs were noted from 1st January, 2007 to 30th June, 2011. Following were noted: demographics, premedication (if any), diagnosis, chemotherapy (regimen, cycles), medication history, and alteration in the treatment or co morbidities, ADRs (severity and management). Adverse drug reactions were noted by patient interview, collaborating with information on file, recording changes in the prescribing chart and investigations, consulting the doctor on duty. RESULTS: During this study period, there were total of 14,475 visits of patients from which 2500 ADRs were recorded. Maximum number of ADRs were noted with platinum compounds (25.52%) followed by pyrimidine antagonists (19.88%). The most common malignancy reported in our hospital was Carcinoma breast (20%) followed by leukemia (12%) and Ca ovary (12%). Alopecia (27.76%) was the most common ADR followed by anemia (7.48%), thrombocytopenia (6.96%) and constipation (6.16%). CONCLUSION: Alopecia is the most common ADR and platinum compounds were responsible for the maximum number of ADRs. The most common carcinoma reported during this period was carcinoma breast. PMID- 26905172 TI - Mixed germ cell tumor in a teenager: A rare entity. PMID- 26905173 TI - Occurrence of precancerous lesion in the post nuclear crisis condition. PMID- 26905174 TI - Bladder cancer presenting with spontaneous subcapsular urinoma of kidney. PMID- 26905175 TI - Adrenal tumors: An experience of 10 years in a single surgical unit. AB - INTRODUCTION: Most of the adrenal masses are discovered incidentally by imaging techniques for reasons unrelated to adrenal diseases. Treatment is based on various factors such as, nature of adrenal mass, age of presentation, size of tumor, and the functional status of tumor. We report a series of 14 consecutive cases of adrenal tumors treated in a single surgical unit in our hospital. AIM: The aim of this study was to evaluate the clinical profile and outcome of treatment of adrenal tumors treated in a surgical unit. MATERIALS AND METHODS: It is a retrospective study data of 14 cases of adrenal tumors treated in a single surgical unit in University Hospital over 10 years have been analyzed. Various parameters such as gender, age, size of tumor, functional status, histopathology, type of management, and outcome have been reviewed. RESULTS: A total of 14 patients with adrenal masses were seen over a 10 year period (1997-2006). All were referred cases, either from endocrinology or medicine wards. There were seven female and seven male patients. Mean age of patients was 48.6 years (range 14-60 years). Mean size of tumor was 8.0 cm (5.9 cm for benign tumors and 9.7 cm for malignant tumors). There were six cases of adrenal carcinoma, four cases of adrenal myelolipoma, two cases of pheochromocytoma, and one each case of adrenal hyperplasia and histoplasmosis. There were only two functional tumors. All, except two malignant cases were treated operatively. A total of 5 year survival was 100% in benign cases and 27% in malignant tumors. CONCLUSION: Adrenal tumors need to be assessed for their functional status and malignant potential prior to treatment. Surgical excision is usually curative for benign lesion. Among malignant tumors the benefits of surgery depend on local extent and metastatic status of tumors. PMID- 26905176 TI - Pulsed Field Gradient NMR with Sigmoid Shape Gradient Sampling To Produce More Detailed Diffusion Ordered Spectroscopy Maps of Real Complex Mixtures: Examples with Medicine Analysis. AB - NMR diffusion measurements are based on signal attenuation. In the case of complex mixtures for which some molecules are diffusing quickly while others are significantly slower, it is challenging to obtain a diffusion ordered spectroscopy (DOSY)-type 2D map giving reliable information on all molecules. In this paper, we propose a new gradient sampling approach based on a sigmoid shape allowing the acquisition of a significant number of points for both the fast and slow diffusing molecules. We applied this new gradient sampling strategy to deformulate two medicines whose composition was known (Esomeprazole) or unknown (Mebendazole). PFG NMR associated with a sigmoid gradient ramp is an exciting strategy to study drugs as a whole, i.e., the active ingredient(s) and excipients. PMID- 26905177 TI - Changes in ganglion cell physiology during retinal degeneration influence excitability by prosthetic electrodes. AB - OBJECTIVE: Here we investigate ganglion cell physiology in healthy and degenerating retina to test its influence on threshold to electrical stimulation. APPROACH: Age-related Macular Degeneration and Retinitis Pigmentosa cause blindness via outer retinal degeneration. Inner retinal pathways that transmit visual information to the central brain remain intact, so direct electrical stimulation from prosthetic devices offers the possibility for visual restoration. Since inner retinal physiology changes during degeneration, we characterize physiological properties and responses to electrical stimulation in retinal ganglion cells (RGCs) of both wild type mice and the rd10 mouse model of retinal degeneration. MAIN RESULTS: Our aggregate results support previous observations that elevated thresholds characterize diseased retinas. However, a physiology-driven classification scheme reveals distinct sub-populations of ganglion cells with thresholds either normal or strongly elevated compared to wild-type. When these populations are combined, only a weakly elevated threshold with large variance is observed. The cells with normal threshold are more depolarized at rest and exhibit periodic oscillations. SIGNIFICANCE: During degeneration, physiological changes in RGCs affect the threshold stimulation currents required to evoke action potentials. PMID- 26905178 TI - Characterization of biofilm formation in natural water subjected to low-frequency electromagnetic fields. AB - Electromagnetic field (EMF) treatment has proven to be effective against mineral scaling in water systems. Therefore, it should be assessed for the treatment of other deposits such as biofilms. In this study, a commercial device producing low frequency EMF (1-10 kHz) was applied to a reactor fed with natural water for 45 days. The treatment promoted the concentration of microorganisms in suspension and limited the amount of sessile microorganisms in the biofilm, as determined by the measurement of total DNA, qPCR and microscopy. The structure of the bacterial community was assessed by t-RFLP and pyrosequencing analysis. The results showed that EMF treatment affected both planktonic and sessile community composition. EMFs were responsible for a shift in classes of Proteobacteria during development of the biofilm. It may be speculated that the EMF treatment affected particle solubility and/or microorganism hydration. This study indicated that EMFs modulated biofilm formation in natural water. PMID- 26905179 TI - Medium-term outcomes after pulmonary valve replacement with the Freestyle valve for congenital heart disease: a case series. AB - OBJECTIVES: The Freestyle valve may be used for pulmonary valve replacement (PVR). Whether its stentless design and anticalcification treatment improve durability relative to alternative bioprostheses, however, is unknown and long term data are lacking. METHODS: We performed a retrospective review of all Freestyle PVRs performed by a single surgeon in two institutions. All patients were contacted for follow-up to establish survival, New York Heart Association class and reintervention. Up to date, echocardiography was obtained to assess valve function. Perioperative factors associated with structural valve dysfunction (SVD) were assessed using Cox regression. RESULTS: Between 2000 and 2014, PVR with a Freestyle valve was performed in 114 patients with congenital heart disease. There were 70 males and 44 females. The median age was 21 years (interquartile range 11-35 years). The median clinical and echocardiographic follow-up was 62 months (interquartile range 35-115 months, n = 110) and 58 months (interquartile range 30-93 months, n = 107), respectively. Follow-up was complete for 107 of 114 patients (94%). The survival rate was 95% at 5 years and 91% at 10 years. The rate of freedom from SVD at 5 years was 82%, and at 10 years was 61%. The reintervention-free survival rate was 85% at 5 years, and 71% at 10 years. CONCLUSION: The Freestyle valve in the pulmonary position in a congenital population is associated with low medium-term incidences of SVD and reintervention. It performs equally well to the homograft when a conduit is required and can be considered a valid alternative to stented bioprostheses when PVR alone is required. PMID- 26905180 TI - The power of surgery. PMID- 26905181 TI - Paediatric mechanical circulatory support with Berlin Heart EXCOR: development and outcome of a 23-year experience. AB - This paper reviews the development and establishment of the Berlin Heart EXCOR(r) (BHE(r)) as a paediatric mechanical circulatory support and reports our entire experience with regard to indications, timing of implantation and explantation and outcome. The Berlin group reported the first successful paediatric bridge to transplantation using a pulsatile pneumatic paracorporeal biventricular assist device, the BHE(r), in 1990 in an 8-year-old boy with end-stage heart failure and coarctation of the aorta. This experience prompted them to develop miniaturized pump systems for children through the company Berlin Heart Mediproduct GmbH. The development and production of BHE(r) to support paediatric patients with heart failure then began. Between 1990 and 2013, the BHE(r) has been implanted in 122 patients (median age 8.64 years, range 3 days to 17 years) with heart failure, who were inotrope-dependent or switched from extracorporeal membrane oxygenation support or had postcardiotomy low-output syndrome. Thirty-five patients were <1 year old (median 125 days). The aetiology of heart failure included cardiomyopathy in 56 (median age 9.14 years), fulminant myocarditis in 17 (median age 8.2 years), end-stage congenital heart disease in 18 (median age 6.4 years), postcardiotomy heart failure (after correction of congenital heart disease) in 28 (median age 9.6 years) and transplant graft failure in 3 (median age 12.5 years). The overall median duration of implantation was 63.6 (range 1-841) days. Fifty six children eventually underwent orthotopic heart transplantation. Eighteen patients had myocardial recovery and were weaned successfully. They had entirely normal cardiac function after a range of 4-10 years after surgery. At the time of this report, five patients were still on support, with a duration of 354-369 days. Forty-three patients died on the system from loss of peripheral circulatory resistance, multiorgan damage, sepsis or haemorrhagic or thrombotic complications. Re-exploration because of bleeding was necessary in 22 patients. Pump exchange because of thrombus formation in the valves was necessary 35 times. With the introduction of a modified anticoagulation regimen in 2000, the pump exchange rate has decreased. The BHE(r) can reliably support the circulation at any age for long periods with good results. It is now an established treatment for children with heart failure of any aetiology. PMID- 26905182 TI - Adequate lymphadenectomy in patients with oesophageal squamous cell carcinoma: resecting the minimal number of lymph node stations. AB - OBJECTIVES: The seventh edition of the American Joint Committee on Cancer (AJCC) tumour-node-metastasis (TNM) staging system for oesophageal cancer did not define the minimal requirement for an adequate extent of lymphadenectomy in patients with oesophageal cancer. This study aimed to define the minimum number of lymph node (LN) stations to be resected in patients with oesophageal squamous cell carcinoma (OSCC). METHODS: We conducted a retrospective review of clinicopathological data from 2033 patients with OSCC undergoing complete resection between August 2005 and September 2013. An ordinal logistic regression analysis was used to identify the variables associated with revised N (rN) staging progression and indices that could be used in the stratified analysis. To determine the optimal number of resected LN stations, we compared the overall survival hazard ratio between groups with different numbers of LN stations using a Cox's proportional hazards regression model. The highest chi(2) value was deemed the cut-off point. RESULTS: The progression of rN staging was influenced by T-staging, G-staging, tumour length (>3 cm), lymphovascular invasion and number of resected LN stations. According to Cox's proportional hazards regression model, we recommended that at least six LN stations should be removed. Then, we conducted a stratified analysis by G status and tumour length. We found that at least seven LN stations should be removed in patients with G3 or tumour length >3 cm. CONCLUSIONS: For thoracic OSCC, at least six LN stations had to be removed. Furthermore, for patients with G3 or tumour length >3 cm, the recommendation was seven. PMID- 26905183 TI - Myeloid sarcoma of the orbit without systemic recurrence of disease in an adult: A clinicopathological case report. AB - Myeloid sarcoma (MS), also known as granulocytic sarcoma (GS) or chloroma (named for the greenish hue attributed to the pigment of myeloperoxidase [MPO]), is a rare solid tumor with a predilection for the orbit. MS usually occurs in conjunction with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or myeloproliferative disorder (MPS) and may be the harbinger of disease. Therefore, prompt diagnosis is essential for patient survival. We present a rare case of a 61 year old with an isolated orbital MS without active leukemia. PMID- 26905184 TI - Provider Bias Impacts Tidal Volume Selection and Ventilator Days in Trauma Patients. AB - BACKGROUND: The ARDSnet (Acute Respiratory Distress Syndrome Clinical Network) study demonstrated that low tidal volume (Vt) reduces mortality from ARDS. It is unknown whether low Vt is beneficial in at-risk trauma patients. We hypothesized that Vt selection would be low in accordance with ARDSnet criteria and that subsequent outcomes would be improved. STUDY DESIGN: A 1-year retrospective observational study was conducted on all trauma patients aged 15 years and older and on mechanical ventilation for 48 hours or longer, excluding those with cardiopulmonary disease. Using maximum Vt, we identified low and high Vt groups (<=8 mL/predicted body weight (PBW) and >8 mL/PBW). Data collected included demographic characteristics, lengths of stay, ventilator and ICU days, ARDS, and other complications. RESULTS: A total of 364 patients were identified and organized into low Vt (n = 181) and high Vt (n = 183) groups. There was no difference between groups in age, Injury Severity Score, Glasgow Coma Scale, or mechanism of injury. The rate of ARDS was the same in each group. Patients with a high Vt had lower PBW (63.1 +/- 8.8 vs 71.7 +/- 6.9; p < 0.001), higher BMI(29.7 +/- 6.9 kg/m(2) vs 26.6 +/- 6.5 kg/m(2); p < 0.001), and were more likely to be female. Height was inversely correlated with Vt (r(2) = -0.579; p < 0.001). The high Vt group experienced longer ICU stays (9.9 +/- 8.8 days vs 8.1 +/- 7.9 days; p = 0.045) and more ventilator days (8.55 +/- 10.5 days vs 6.14 +/- 7.4 days; p = 0.015). CONCLUSIONS: Trauma patients receiving high Vt were shorter, had higher BMI, and were more likely to be female. The consequences included longer ICU stays and more ventilator days. Formal calculation of PBW and subsequent Vt is advocated. PMID- 26905185 TI - Risk of Reoperation Within 90 Days of Liver Transplantation: A Necessary Evil? AB - BACKGROUND: The rate and consequences of reoperation after liver transplantation (LT) are unknown in the United States. STUDY DESIGN: Adult patients (n = 10,295; 45% of all LT) undergoing LT from 2009 through 2012 were examined using a linkage of the University HealthSystem Consortium and Scientific Registry of Transplant Recipients databases providing recipient, donor, center, hospitalization, and survival details. Median follow-up was 2 years. Reoperations were identified within 90 days after LT. RESULTS: Overall 90-day reoperation rate after LT was 29.3%. Risk factors for 90-day reoperation included recipients with a history of hemodialysis, severely ill functional status, government insurance, increasing Model for End-Stage Liver Disease score, and increasing donor risk index. Reoperation within 90 days was found to be an independent predictor of adjusted 1 year mortality (odds ratio = 1.8; 95% CI, 1.5-2.1), as was government-provided insurance and increasing donor risk index. Additionally, patients undergoing delayed reoperative intervention (after 30 days) were found to have increased risk of 1-year mortality compared with those undergoing early reoperative intervention (odds ratio = 1.96; 95% CI, 1.4-2.7; p < 0.01). CONCLUSIONS: This is the first national study reporting that nearly one-third of transplant recipients undergo reoperation within 90 days of LT. Although necessary at times, reoperation is associated with increased risk of death at 1 year; however, it appears that the timing of these interventions can be critical, due to the type of intervention required. Early reoperative intervention does not appear to influence long-term outcomes, and delayed intervention (after 30 days) is strongly associated with decreased survival. PMID- 26905186 TI - Impact of Transcatheter Aortic Valve Replacement on Surgical Volumes and Outcomes in a Tertiary Academic Cardiac Surgical Practice. AB - BACKGROUND: Transcatheter aortic valve replacement (TAVR) was FDA approved for the Sapien valve (Edwards Lifesciences) in the United States in November 2011. We sought to examine the impact of TAVR post-FDA approval on aortic valve surgery at our institution. STUDY DESIGN: Prospective data were collected on 573 consecutive patients that underwent surgical aortic valve replacement (SAVR) or TAVR with either the Sapien or Sapien XT from January 1, 2009 through December 31, 2014. RESULTS: Patients were divided into the following groups: SAVR before TAVR (n = 215), SAVR post TAVR (n = 163), and TAVR (n = 195). The 30-day mortality was not different among the 3 groups, but the mortality for the SAVR post TAVR group was better than the SAVR before TAVR group (p = 0.03). Postoperative hospital length of stay, ventilation hours, and atrial fibrillation were all decreased in the TAVR group. The number of isolated SAVRs increased after TAVR from 60 per year in group 1 to 67 per year in group 2. The total number of all isolated aortic valve procedures (SAVR + TAVR) increased from 60 per year to 177 per year. The TAVR group was divided into the following subgroups to examine the procedural learning curve: patients 1 to 50, patients 51 to 100, and patients 101 to 195. Mortality was higher in group 1 (8%) vs group 2 (0%) and group 3 (1%). CONCLUSIONS: Since initiation of the TAVR program at our institution, the total number of aortic valve procedures has increased. Transcatheter aortic valve replacement patients had more preoperative comorbidities, but no difference in postoperative morbidity or mortality and shorter length of stay. Transcatheter aortic valve replacement mortality has continued to improve since the inception of the program. PMID- 26905187 TI - Stage-Specific Prognostic Effect of Race in Patients with Resectable Gastric Adenocarcinoma: An 8-Institution Study of the US Gastric Cancer Collaborative. AB - BACKGROUND: Gastric cancer constitutes a major public health problem. This study sought to evaluate the relevance of race in gastric cancer and its prognostic effect in the overall outcomes of patients with gastric adenocarcinoma. STUDY DESIGN: Patients who underwent curative intent resection of gastric adenocarcinoma in 8 institutions of the US Gastric Cancer Collaborative were included, from 2000 to 2012. Nonparametric descriptive statistics were used to evaluate characteristics of standard demographic data. Multivariate Cox proportional hazards regression was used to identify factors associated with recurrence-free survival and overall survival. RESULTS: There were 1,077 patients included in the study, the majority of whom were of Caucasian race (n = 698, 68%), followed by African-American (n = 164, 15%), Asian (n = 132, 12%), Hispanic (n = 34, 3.2%), and other (n = 49, 4.5%). Clinicopathologic data were similarly distributed among the 5 groups. Mean follow-up was 27.1 months. By multivariate, stage-specific analysis, Asian race was a significant predictor of recurrence (all stages hazard ratio [HR] 0.45 95% CI [0.23, 0.97], p = 0.041) and of overall survival (all stages HR 0.35 95% CI [0.18, 0.68], p = 0.002). Recurrence-free survival was significantly increased in the Asian population compared with the non-Asian population (25th percentile: 38.6 vs 17.7 months, p = 0.0096), as was overall median survival (141 vs 38.8 months, p < 0.001). CONCLUSIONS: Patients of Asian race undergoing curative gastrectomy for gastric adenocarcinoma appear to have a better prognosis stage for stage. Further studies are required to elucidate the underlying etiology of this phenomenon. PMID- 26905188 TI - Impact of Residents on Surgical Outcomes in High-Complexity Procedures. AB - BACKGROUND: There are different views on the effects of resident involvement on surgical outcomes. We hypothesized that resident participation in surgical care does not appreciably alter outcomes. STUDY DESIGN: We analyzed an American College of Surgeons NSQIP subset of inpatients having procedures with high complexity, including 4 surgical specialties (general surgery, cardiothoracic surgery, neurosurgery, and vascular surgery) with the highest mean work relative value units. We evaluated surgical outcomes in patients having procedures performed by the attending surgeon alone, or by the attending surgeon with assistance from at least one surgical resident (PGY1 to PGY>=6). Outcomes measures included operative mortality, composite morbidity, and failure to rescue (FTR). Propensity-score matching minimized the effects of nonrandom assignment of residents to procedures. RESULTS: In 266,411 patients, unmatched comparisons showed significantly higher operative mortality and composite morbidity rates, but decreased FTR, in operations performed with resident involvement. After propensity-score matching, there were small but significant resident-related increases in composite morbidity, but significant improvement in FTR. Senior level resident involvement translated into improved outcomes, especially in cardiothoracic surgery procedures where >63.6% of procedures had PGY>=6 resident involvement. Resident involvement attenuated the significant worsening of operative mortality and FTR associated with multiple serious complications in individual patients. Measures of resource use increased modestly with resident involvement. CONCLUSIONS: We found substantial improvement in FTR with resident involvement, both in unmatched and propensity-matched comparisons. Senior-level resident participation seemed to attenuate, and even improve, surgical outcomes, despite slightly increased resource use. These results provide some reassurance about teaching paradigms. PMID- 26905189 TI - Effects of various cannabinoid ligands on choice behaviour in a rat model of gambling. AB - It is estimated that 0.6-1% of the population in the USA and Canada fulfil the Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM-5) criteria for gambling disorders (GD). To date, there are no approved pharmacological treatments for GD. The rat gambling task (rGT) is a recently developed rodent analogue of the Iowa gambling task in which rats are trained to associate four response holes with different magnitudes and probabilities of food pellet rewards and punishing time-out periods. Similar to healthy human volunteers, most rats adopt the optimal strategies (optimal group). However, a subset of animals show preference for the disadvantageous options (suboptimal group), mimicking the choice pattern of patients with GD. Here, we explored for the first time the effects of various cannabinoid ligands (WIN 55,212-2, AM 4113, AM 630 and URB 597) on the rGT. Administration of the cannabinoid agonist CB1/CB2 WIN 55,212-2 improved choice strategy and increased choice latency in the suboptimal group, but only increased perseverative behaviour, when punished, in the optimal group. Blockade of CB1 or CB2 receptors or inhibition of fatty-acid amide hydrolase did not affect rGT performance. These results suggest that stimulation of cannabinoid receptors could affect gambling choice behaviours differentially in some subgroups of subjects. PMID- 26905190 TI - Dyadic social interaction of C57BL/6 mice versus interaction with a toy mouse: conditioned place preference/aversion, substrain differences, and no development of a hierarchy. AB - Impaired social interaction is a hallmark symptom of many psychiatric diseases, including dependence syndromes (substance use disorders). Helping the addict reorient her/his behavior away from the drug of abuse toward social interaction would be of considerable therapeutic benefit. To study the neural basis of such a reorientation, we have developed several animal models in which the attractiveness of a dyadic (i.e. one-to-one) social interaction (DSI) can be compared directly with that of cocaine as a prototypical drug of abuse. Our models are based on the conditioned place preference (CPP) paradigm. In an ongoing effort to validate our experimental paradigms in C57BL/6 mice to make use of the plethora of transgenic models available in this genus, we found the following: (a) DSI with a live mouse produced CPP, whereas an interaction with an inanimate mouse-like object (i.e. a 'toy mouse'; toy mouse interaction) led to conditioned place aversion - but only in the Jackson substrain (C57BL/6J). (b) In the NIH substrain (C57BL/6N), both DSI and toy mouse interaction produced individual aversion in more than 50% of the tested mice. (c) Four 15 min DSI episodes did not result in the development of an observable hierarchy, that is, dominance/subordination behavior in the overwhelming majority (i.e. 30 of 32) of the tested Jackson mouse pairs. Therefore, dominance/subordination does not seem to be a confounding variable in our paradigm, at least not in C57BL/6J mice. Respective data for NIH mice were too limited to allow any conclusion. The present findings indicate that (a) DSI with a live mouse produces CPP to a greater degree than an interaction with an inanimate object resembling a mouse and that (b) certain substrain differences with respect to CPP/aversion to DSI do exist between the Jax and NIH substrain of C57BL/6 mice. These differences have to be considered when choosing a proper mouse substrain model for investigating the neural basis of DSI reward versus drug reward. PMID- 26905191 TI - Monosodium glutamate intake affect the function of the kidney through NMDA receptor. AB - AIMS: We investigated whether the chronic intake of monosodium glutamate (MSG) with food affects kidney function, and renal response to glycine. We also established if the NMDA receptors are involved in the changes observed. MAIN METHODS: Male Wistar rats (5weeks old) were fed a diet supplemented with MSG (3g/kg b.w./day), five days a week, and spontaneous ingestion of a 1% MSG solution during 16weeks. NaCl rats were fed a diet with NaCl (1g/kg b.w./day) and 0.35% NaCl solution at the same frequency and time. Control group was fed with normal chow and tap water. We utilized clearance techniques to examine glomerular filtration rate (GFR) and cortical renal plasma flow (CRPF) response to glycine and glycine+MK-801 (antagonist NMDA-R), and we determined NMDA-R1 in kidney by immunohistochemistry. KEY FINDINGS: The addition of MSG in the diet of rats increased both GFR and CRPF with an increase of absolute sodium reabsorption. However, hyperfiltration was accompanied with a normal response to glycine infusion. Immunostain of kidney demonstrate that the NMDA receptor is upregulated in rats fed with MSG diet. NMDA-R antagonist MK-801 significantly reduced both the GFR and CRPF; however the percentage of reduction was significantly higher in the group MSG. MK-801 also reduces fractional excretion of water, sodium and potassium in the three groups. SIGNIFICANCE: Renal NMDAR may be conditioned by the addition of MSG in the diet, favoring the hyperfiltration and simultaneously Na retention in the body. PMID- 26905192 TI - The role of curcumin in streptozotocin-induced hepatic damage and the trans differentiation of hepatic stellate cells. AB - Diabetic patients frequently suffer from non-alcoholic steatohepatitis. The current study aimed to investigate the role of curcumin and the response of hepatic stellate cells in streptozotocin (STZ)-induced hepatic damage. Sixty male rats were divided into three groups. The normal control injected with a citrate buffer vehicle and the diabetic control group which was injected intraperitoneally (IP) with a single-dose of streptozotocin (50mg/kg body weight) and a diabetic group was treated with an oral dose of curcumin at 80 mg/kg body weight daily for 60 days. Curcumin effectively counteracts oxidative stress mediated hepatic damage and improves biochemical parameters. Alpha-smooth muscle actin (alpha-SMA) was significantly reduced, and insulin antibodies showed strong positive immunoreactivity with curcumin administration. These results optimistically demonstrate the potential use of curcumin, which is attributed to its antiradical/antioxidant activities and its potential beta-cell regenerative properties. Also, it has the capability to encourage the trans-differentiation of hepatic stellate cells into insulin-producing cells for a period of time. In addition, as it is an anti-fibrotic mediator that inhibits hepatic stellate cell activation and the transition to myofibroblast-like cells, this suggests the possibility of considering curcumin's novel therapeutic effects in reducing hepatic dysfunction in diabetic patients. PMID- 26905193 TI - Biological characteristics of mouse skin melanocytes. AB - The objective of this research was to evaluate the optimal passage number according to the biological characteristics of mouse skin melanocytes from different passages. Skin punch biopsies harvested from the dorsal region of 2-day old mice were used to establish melanocyte cultures. The cells from passage 4, 7, 10 and 13 were collected and evaluated for their melanogenic activity. Histochemical staining for tyrosinase (TYR) activity and immunostaining for the melanocyte specific markers including S-100 antigen, TYR, tyrosinase related protein 1 (TYRP1), tyrosinase related protein 2 (TYRP2) and micropthalmia associated transcription factor (MITF) confirmed purity and melanogenic capacity of melanocytes from different passages, with better melanogenic activity of passage 10 and 13 cells being observed. Treatment of passage 13 melanocytes with alpha-melanocyte stimulating hormone (alpha-MSH) showed increased expression of MITF, TYR and TYRP2 mRNA. However, considering the TYR mRNA dramatically high expression which is the characteristics of melanoma cells, melanocytes from passage 10 was the optimal passage number for the further research. Our results demonstrate culture of pure populations of mouse melanocytes to at least 10 passages and illustrate the potential utility of passage 10 cells for studies of intrinsic and extrinsic regulation of genes controlling pigmentation and coat color in mouse. PMID- 26905194 TI - Effect of varying the salt and fat content in Cheddar cheese on aspects of the performance of a commercial starter culture preparation during ripening. AB - Production of healthier reduced-fat and reduced-salt cheeses requires careful selection of starter bacteria, as any substantial alterations to cheese composition may prompt changes in the overall performance of starters during cheese ripening. Therefore, it is important to assess the effect of compositional alterations on the individual strain response during cheese ripening for each optimised cheese matrix. In the current study, the effect of varying fat and salt levels in Cheddar cheese on the performance of a commercial Lactococcus lactis culture preparation, containing one L. lactis subsp. lactis strain and one L. lactis subsp. cremoris strain was investigated. Compositional variations in fat or salt levels did not affect overall starter viability, yet reduction of fat by 50% significantly delayed non-starter lactic acid bacteria (NSLAB) populations at the initial ripening period. In comparison to starter viability, starter autolysis, as measured by release of intracellular lactate dehydrogenase (LDH) or post-proline dipeptidyl aminopeptidase (Pep X) into cheese juices, decreased significantly with lower salt addition levels in full-fat Cheddar. Conversely, reducing fat content of cheese resulted in a significantly higher release of intracellular Pep X, and to a lesser extent intracellular LDH, into juices over ripening. Flow cytometry (FCM) indicated that the permeabilised and dead cell sub populations were generally lower in juices from cheeses with reduced salt content, however no significant differences were observed between different salt and fat treatments. Interestingly, fat reductions by 30 and 50% in cheeses with reduced or half added salt contents appeared to balance out the effect of salt, and enhanced cell permeabilisation, cell death, and also cell autolysis in these variants. Overall, this study has highlighted that alterations in both salt and fat levels in cheese influence certain aspects of starter performance during ripening, including autolysis, permeabilisation, and intracellular enzyme release. However, it may be possible to reduce the fat and salt content of Cheddar cheese by 30 or 50%, respectively, without largely altering permeabilised and dead cell sub-populations and, in turn, the amount of released intracellular Pep X activity, such that these performance parameters are similar to those observed for control full-fat, full-salt Cheddar cheese. PMID- 26905195 TI - Promotion of adipogenesis by 15-(S)-hydroxyeicosatetraenoic acid. AB - Excess adipogenesis is a characteristic of obesity, which is associated with serious health problem, including type 2 diabetes. Here, to better understand the mechanisms for the development of adipocytes, we investigated the regulatory role of 15-(S)-hydroxyeicosatetraenoic acid (15(S)-HETE) in adipogenesis by treating 3T3-L1 murine preadipocytes and human bone marrow mesenchymal stem cells (hBMSCs) with 15(S)-HETE. In the 3T3-L1 study, 15(S)-HETE stimulated lipid accumulation and enhanced expression of adipogenic markers such as peroxisome proliferator activated receptor gamma (PPARgamma), yet reduced the activity of factor negatively controlling adipogenesis, such as the 5'-AMP-activated protein kinase. In the early stage of adipogenesis, 15(S)-HETE increased activation of protein kinase B and expression of CCAAT/enhancer-binding protein (C/EBP)beta and C/EBPdelta. Finally, 15(S)-HETE promoted adipogenesis in hBMSCs, and resulted in increased lipid accumulation and expression of adipogenic markers. In conclusion, 15(S)-HETE functions as a natural PPARgamma agonist and enhances adipogenesis. Our findings may provide the basis for the development of novel therapeutic measures to treat obesity. PMID- 26905196 TI - The initiation of lateral roots in the primary roots of maize (Zea mays L.) implies a reactivation of cell proliferation in a group of founder pericycle cells. AB - The initiation of lateral roots (LRs) has generally been viewed as a reactivation of proliferative activity in pericycle cells that are committed to initiate primordia. However, it is also possible that pericycle founder cells that initiate LRs never cease proliferative activity but rather are displaced to the most distal root zones while undertaking successive stages of LR initiation. In this study, we tested these two alternative hypotheses by examining the incorporation of 5-bromo-2'-deoxyuridine (BrdU) into the DNA of meristematic root cells of Zea mays. According to the values for the length of the cell cycle and values for cell displacement along the maize root, our results strongly suggest that pericycle cells that initiate LR primordia ceased proliferative activity upon exiting the meristematic zone. This finding is supported by the existence of a root zone between 4 and 20mm from the root cap junction, in which neither mitotic cells nor labelled nuclei were observed in phloem pericycle cells. PMID- 26905197 TI - Gene expression and flavonolignan production in fruits and cell cultures of Silybum marianum. AB - The hepatoprotectant flavonolignan silymarin (Sm) is synthesized through 4 coumaroyl-CoA, which enters both the flavonoid and the monolignol pathway giving the two immediate precursors taxifolin (Tx) and coniferyl alcohol (CA), respectively. Sm formation occurs via oxidative radicalization of Tx and CA and is accumulated at high levels at final stages of maturation of Silybum marianum fruits. By contrast, Sm production is severely reduced in cell cultures of this species, although suspensions are able to excrete Sm compounds into the medium upon elicitation with methyl jasmonate (MeJA) or cyclodextrins (CD). Knowledge of gene expression is important to understand Sm dynamics and to develop strategies aimed at increasing production by means of cell cultures but, to date, only one gene of the pathway (chalcone synthase, SmCHS) has been cloned. Therefore, to elucidate the relationship between expression of Sm pathway genes and production of these metabolites, four cDNA fragments of genes putatively involved in flavonolignan biosynthesis, chalcone isomerase, flavanone 3-hydroxylase, flavonol 3'-hydroxylase and cinnamyl alcohol dehydrogenase, were isolated from Sm producing S. marianum fruits and their expression, together with that of the SmCHS, were studied both in fruits at different maturation stages and in elicited cell suspensions. Combined results at both transcript expression and metabolite levels at three different stages of fruit maturation revealed that the formation of the flavonoid moiety precedes flavonolignan biosynthesis, being Sm accumulation associated to expression of the monolignol pathway. There was not detectable accumulation of transcripts in cell suspensions, however, elicitation with MeJA or CD notably induced expression of the studied fragments. These results indicate that the five genes expressed during maturation of S. marianum fruits may contribute to observed increases in flavonolignan accumulation upon treatment of cell cultures with elicitors. PMID- 26905198 TI - Cardiomyocytes Derived from MHC-Homozygous Induced Pluripotent Stem Cells Exhibit Reduced Allogeneic Immunogenicity in MHC-Matched Non-human Primates. AB - Induced pluripotent stem cells (iPSCs) can serve as a source of cardiomyocytes (CMs) to treat end-stage heart failure; however, transplantation of genetically dissimilar iPSCs even within species (allogeneic) can induce immune rejection. We hypothesized that this might be limited by matching the major histocompatibility complex (MHC) antigens between the donor and the recipient. We therefore transplanted fluorescence-labeled (GFP) iPSC-CMs donated from a macaque with homozygous MHC haplotypes into the subcutaneous tissue and hearts of macaques having heterozygous MHC haplotypes (MHC-matched; group I) or without identical MHC alleles (group II) in conjunction with immune suppression. Group I displayed a higher GFP intensity and less immune-cell infiltration in the graft than group II. However, MHC-matched transplantation with single or no immune-suppressive drugs still induced a substantial host immune response to the graft. Thus, the immunogenicity of allogeneic iPSC-CMs was reduced by MHC-matched transplantation although a requirement for appropriate immune suppression was retained for successful engraftment. PMID- 26905199 TI - EVA1A/TMEM166 Regulates Embryonic Neurogenesis by Autophagy. AB - Self-renewal and differentiation of neural stem cells is essential for embryonic neurogenesis, which is associated with cell autophagy. However, the mechanism by which autophagy regulates neurogenesis remains undefined. Here, we show that Eva1a/Tmem166, an autophagy-related gene, regulates neural stem cell self-renewal and differentiation. Eva1a depletion impaired the generation of newborn neurons, both in vivo and in vitro. Conversely, overexpression of EVA1A enhanced newborn neuron generation and maturation. Moreover, Eva1a depletion activated the PIK3CA AKT axis, leading to the activation of the mammalian target of rapamycin and the subsequent inhibition of autophagy. Furthermore, addition of methylpyruvate to the culture during neural stem cell differentiation rescued the defective embryonic neurogenesis induced by Eva1a depletion, suggesting that energy availability is a significant factor in embryonic neurogenesis. Collectively, these data demonstrated that EVA1A regulates embryonic neurogenesis by modulating autophagy. Our results have potential implications for understanding the pathogenesis of neurodevelopmental disorders caused by autophagy dysregulation. PMID- 26905200 TI - ER Stress and Autophagic Perturbations Lead to Elevated Extracellular alpha Synuclein in GBA-N370S Parkinson's iPSC-Derived Dopamine Neurons. AB - Heterozygous mutations in the glucocerebrosidase gene (GBA) represent the strongest common genetic risk factor for Parkinson's disease (PD), the second most common neurodegenerative disorder. However, the molecular mechanisms underlying this association are still poorly understood. Here, we have analyzed ten independent induced pluripotent stem cell (iPSC) lines from three controls and three unrelated PD patients heterozygous for the GBA-N370S mutation, and identified relevant disease mechanisms. After differentiation into dopaminergic neurons, we observed misprocessing of mutant glucocerebrosidase protein in the ER, associated with activation of ER stress and abnormal cellular lipid profiles. Furthermore, we observed autophagic perturbations and an enlargement of the lysosomal compartment specifically in dopamine neurons. Finally, we found increased extracellular alpha-synuclein in patient-derived neuronal culture medium, which was not associated with exosomes. Overall, ER stress, autophagic/lysosomal perturbations, and elevated extracellular alpha-synuclein likely represent critical early cellular phenotypes of PD, which might offer multiple therapeutic targets. PMID- 26905201 TI - Functional Neurons Generated from T Cell-Derived Induced Pluripotent Stem Cells for Neurological Disease Modeling. AB - Modeling of neurological diseases using induced pluripotent stem cells (iPSCs) derived from the somatic cells of patients has provided a means of elucidating pathogenic mechanisms and performing drug screening. T cells are an ideal source of patient-specific iPSCs because they can be easily obtained from samples. Recent studies indicated that iPSCs retain an epigenetic memory relating to their cell of origin that restricts their differentiation potential. The classical method of differentiation via embryoid body formation was not suitable for T cell derived iPSCs (TiPSCs). We developed a neurosphere-based robust differentiation protocol, which enabled TiPSCs to differentiate into functional neurons, despite differences in global gene expression between TiPSCs and adult human dermal fibroblast-derived iPSCs. Furthermore, neurons derived from TiPSCs generated from a juvenile patient with Parkinson's disease exhibited several Parkinson's disease phenotypes. Therefore, we conclude that TiPSCs are a useful tool for modeling neurological diseases. PMID- 26905202 TI - Alternative Routes to Induced Pluripotent Stem Cells Revealed by Reprogramming of the Neural Lineage. AB - During the reprogramming of mouse embryonic fibroblasts (MEFs) to induced pluripotent stem cells, the activation of pluripotency genes such as NANOG occurs after the mesenchymal to epithelial transition. Here we report that both adult stem cells (neural stem cells) and differentiated cells (astrocytes) of the neural lineage can activate NANOG in the absence of cadherin expression during reprogramming. Gene expression analysis revealed that only the NANOG+E-cadherin+ populations expressed stabilization markers, had upregulated several cell cycle genes; and were transgene independent. Inhibition of DOT1L activity enhanced both the numbers of NANOG+ and NANOG+E-cadherin+ colonies in neural stem cells. Expressing SOX2 in MEFs prior to reprogramming did not alter the ratio of NANOG colonies that express E-cadherin. Taken together these results provide a unique pathway for reprogramming taken by cells of the neural lineage. PMID- 26905204 TI - Influence of DNA-methylation on zinc homeostasis in myeloid cells: Regulation of zinc transporters and zinc binding proteins. AB - The distribution of intracellular zinc, predominantly regulated through zinc transporters and zinc binding proteins, is required to support an efficient immune response. Epigenetic mechanisms such as DNA methylation are involved in the expression of these genes. In demethylation experiments using 5-Aza-2' deoxycytidine (AZA) increased intracellular (after 24 and 48h) and total cellular zinc levels (after 48h) were observed in the myeloid cell line HL-60. To uncover the mechanisms that cause the disturbed zinc homeostasis after DNA demethylation, the expression of human zinc transporters and zinc binding proteins were investigated. Real time PCR analyses of 14 ZIP (solute-linked carrier (SLC) SLC39A; Zrt/IRT-like protein), and 9 ZnT (SLC30A) zinc transporters revealed significantly enhanced mRNA expression of the zinc importer ZIP1 after AZA treatment. Because ZIP1 protein was also enhanced after AZA treatment, ZIP1 up regulation might be the mediator of enhanced intracellular zinc levels. The mRNA expression of ZIP14 was decreased, whereas zinc exporter ZnT3 mRNA was also significantly increased; which might be a cellular reaction to compensate elevated zinc levels. An enhanced but not significant chromatin accessibility of ZIP1 promoter region I was detected by chromatin accessibility by real-time PCR (CHART) assays after demethylation. Additionally, DNA demethylation resulted in increased mRNA accumulation of zinc binding proteins metallothionein (MT) and S100A8/S100A9 after 48h. MT mRNA was significantly enhanced after 24h of AZA treatment also suggesting a reaction of the cell to restore zinc homeostasis. These data indicate that DNA methylation is an important epigenetic mechanism affecting zinc binding proteins and transporters, and, therefore, regulating zinc homeostasis in myeloid cells. PMID- 26905203 TI - GATA Factor-G-Protein-Coupled Receptor Circuit Suppresses Hematopoiesis. AB - Hematopoietic stem cells (HSCs) originate from hemogenic endothelium within the aorta-gonad-mesonephros (AGM) region of the mammalian embryo. The relationship between genetic circuits controlling stem cell genesis and multi-potency is not understood. A Gata2 cis element (+9.5) enhances Gata2 expression in the AGM and induces the endothelial to HSC transition. We demonstrated that GATA-2 rescued hematopoiesis in +9.5(-/-) AGMs. As G-protein-coupled receptors (GPCRs) are the most common targets for FDA-approved drugs, we analyzed the GPCR gene ensemble to identify GATA-2-regulated GPCRs. Of the 20 GATA-2-activated GPCR genes, four were GATA-1-activated, and only Gpr65 expression resembled Gata2. Contrasting with the paradigm in which GATA-2-activated genes promote hematopoietic stem and progenitor cell genesis/function, our mouse and zebrafish studies indicated that GPR65 suppressed hematopoiesis. GPR65 established repressive chromatin at the +9.5 site, restricted occupancy by the activator Scl/TAL1, and repressed Gata2 transcription. Thus, a Gata2 cis element creates a GATA-2-GPCR circuit that limits positive regulators that promote hematopoiesis. PMID- 26905205 TI - A new antimicrobial protein from the anterior midgut of Triatoma infestans mediates Trypanosoma cruzi establishment by controlling the microbiota. AB - The Reduviid Triatoma infestans is a vector for the protozoan Trypanosoma cruzi, the etiological agent of Chagas disease. The parasite must address the defense molecules and microbiota that colonize the anterior midgut of T. infestans. To obtain insight into T. cruzi - microbiota interactions in triatomine insects, we characterized a new antimicrobial product from the anterior midgut of T. infestans (TiAP) that may be involved in these relationships. The TiAP DNA fragment was cloned and expressed in a bacterial system, and the effect of the protein on bacteria and T. cruzi was evaluated by RNAi, qPCR and antimicrobial experiments. The number of T. cruzi in T. infestans anterior midguts was significantly lower in TiAP knockdown insects than in unsilenced groups. We also verified that the amount of bacteria in silenced T. infestans is approximately 600-fold higher than in unsilenced insects by qPCR. The 327-bp cDNA fragment that encodes mature TiAP was cloned into the pET-14b vector and expressed fused to a His-tag in Escherichia coli C43. The recombinant protein (rTiAP) was purified using an Ni-NTA column, followed by a HiTrap SP column. According to a trypanocidal assay, rTiAP did not interfere with the viability of T. cruzi trypomastigotes. Moreover, in antimicrobial experiments using E. coli and Micrococcus luteus, the protein was only bacteriostatic for Gram-negative bacteria. The data indicate that infection by T. cruzi increases the expression of TiAP to modulate the microbiota. The inhibition of microbiota growth by TiAP is important for parasite establishment in the T. infestans anterior midgut. PMID- 26905206 TI - Novel binding patterns between ganoderic acids and neuraminidase: Insights from docking, molecular dynamics and MM/PBSA studies. AB - Recently, ganoderic acids (GAs) give rise to the attractive candidates of novel neuraminidase (NA) inhibitors. However, there is still no evident conclusion about their binding patterns. To this end, docking, molecular dynamics and MM/PBSA methods were combined to study the binding profiles of GAs with the N1 protein and familiar H274Y and N294S mutations (A/Vietnam/1203/04 stain). It was found that the binding affinities of ganoderic acid DM and Z (DeltaGbind, -16.83 and -10.99 kcal mol(-1)) are comparable to that of current commercial drug oseltamivir (-23.62 kcal mol(-1)). Electrostatic interaction is the main driving force, and should be one important factor to evaluate the binding quality and rational design of NA inhibitors. The 150-loop residues Asp151 and Arg152 played an important role in the binding processes. Further analysis revealed that ganoderic acid DM is a potential source of anti-influenza ingredient, with novel binding pattern and advantage over oseltamivir. It had steric hindrance on the 150 cavity of N1 protein, and exerted activities across the H274Y and N294S mutations. This work also pointed out how to effectively design dual-site NA inhibitors and reinforce their affinities. These findings should prove valuable for the in-depth understanding of interactions between NA and GAs, and warrant the experimental aspects to design novel anti-influenza drugs. PMID- 26905207 TI - Tetrel bonds between PySiX3 and some nitrogenated bases: Hybridization, substitution, and cooperativity. AB - Ab initio calculations have been performed to study the influence of hybridization, substitution, and cooperativity on the tetrel bond in the complexes of PySiX3 (Py=pyridine and X=halogen). The tetrel bond becomes stronger in the order of p-PySiF3?NCH(sp)50mm than <=50mm (OR 4.91, 95% CI 2.73-8.82) and six and ten times greater for MI >33% to <=66% (OR, 5.70; 95% CI, 2.25-14.5) and >66% (OR 10.2, 95% CI 4.11-25.4), respectively, than <=33%. Best-model false-negative (0%) and positive (57.2%) rates demonstrated marked improvement over traditional risk-stratification false-negative (1.5%) and positive (76.2%) rates (c-statistic 0.77, 95% CI 0.72-0.82). CONCLUSIONS: Tumor diameter is an important predictor of LD. Our risk model, containing modified forms of MI and TD, yielded a lower false negative rate and can significantly decrease the number of lymphadenectomies performed on low-risk women. PMID- 26905211 TI - Sentinel lymph node mapping with staging lymphadenectomy for patients with endometrial cancer increases the detection of metastasis. AB - OBJECTIVES: To compare the performance of sentinel lymph node (SLN) mapping with staging lymphadenectomy versus staging lymphadenectomy alone for the detection of metastasis and the use of adjuvant therapies in patients with endometrial cancer. METHODS: All patients with apparent early-stage endometrial cancer (n=780) who underwent robotic-assisted hysterectomy with pelvic+/-aortic lymphadenectomy from July-2006 to June-2013 were compared [pelvic+/-aortic lymphadenectomy (n=661) versus SLN-mapped cases with pelvic+/-aortic lymphadenectomy (n=119)]. Isosulfan blue and indocyanine-green with near-infrared imaging were used for SLN mapping. Clinico-pathological data, FIGO stage, GOG risk category, and adjuvant therapies were compared. RESULTS: Non-mapped and mapped cases were comparable with respect to BMI, histology, depth-of-invasion, and lympho-vascular space invasion. The mapped group had more pelvic lymph node (LN) harvested compared to non-mapped group (26.4+/-10.5 vs. 18.8+/-8.5, p<0.001). Aortic LN yields were identical for both groups (9.0+/-5.6 vs. 9.0+/-6.0). The mapped group had more LN metastasis detected (30.3% vs. 14.7%, p<0.001), more stage IIIC (30.2% vs. 14.5%, p<0.001), more GOG high-risk cases (32.8% vs. 21.8%, p=0.013), and received more chemotherapy+radiation (28.6% vs. 16.3%, p<0.003). The SLN was the only metastasis in 18 (50%) mapped cases with positive nodes. The SLN false negative rate was 1/36 (2.8%). Micrometastases or isolated tumor cells were identified in 22/35 (62.9%) SLN metastases. Multivariate analysis demonstrated that SLN mapping imparted a significant effect on the detection of metastatic disease [adjusted OR=3.29, p<0.001]. CONCLUSIONS: The performance of SLN mapping with staging lymphadenectomy increased the detection of lymph node metastasis and was associated with more use of adjuvant therapies. PMID- 26905212 TI - Towards the implementation of the Stockholm Convention in Spain: Five-year monitoring (2008-2013) of POPs in air based on passive sampling. AB - Within the framework of the Spanish monitoring program, this study reports on air concentration of DDTs, HCB, HCHs, NDL-PCBs, DL-PCBs, PCDD/Fs and PBDEs measured during the five-year sampling period 2008-2013. Spanish coastal remote and urban locations were studied using PUF disk passive air samplers which were deployed and collected every three months. Despite the wide range of concentrations measured for most contaminants, a common pattern of relative abundance (median values): NDL-PCBs (36.6 pg/m(3)) > HCB (24.8 pg/m(3)) ~ HCHs (17.9 pg/m(3)) ~ DDTs (16.6 pg/m(3)) > PBDEs (3.65 pg/m(3)) > DL-PCBs (2.99 pg/m(3)) >> PCDD/Fs (0.060 pg/m(3)) was found fairly consistent across most seasons and locations. Nevertheless, important variations in yearly concentrations were measured for different POPs. In general, higher levels of DDTs, HCHs, NDL-PCBs, DL-PCBs and PCDD/Fs were found in urban sites highlighting important differences between remote and urban sampling locations for most target contaminants. Greater concentrations of the banned organochlorine pesticides in urban locations suggested the existence of unexpected pointed sources that need to be further investigated and characterized. The limited dataset collected thus far rendered no clear temporal trends for most study target compounds, which emphasizes the necessity of the Spanish monitoring program future maintenance in time. PMID- 26905213 TI - Influence of thoracic epidural anesthesia on gastric oxygenation during hypothermia and hemorrhage. AB - OBJECTIVE: Hypothermia preserves gastric mucosal microvascular oxygenation (MUHbO2) during hemorrhagic shock. Additionally, hypothermia activates the sympathetic nervous system that leads to the release of vasopressin. The aim of this study was to evaluate whether the effect of hypothermia is mediated via the sympathetic nervous system and/or via vasopressin. METHODS: In prospective and randomized experiments on five anesthetized dogs (foxhounds, cross-over design, 6 groups with n=5 per group) we analyzed the effects of hemorrhage on MUHbO2 during mild hypothermia (HT, 34 degrees C), during additional thoracic epidural anesthesia (HT/TEA) and during additional vasopressin V1 receptor blockade (HT/VB). As control groups, effects of hemorrhage were studied under normothermia alone (NT), during additional thoracic epidural anesthesia (NT/TEA) and during additional vasopressin V1 receptor blockade (NT/VB). RESULTS: Hemorrhage decreased MUHbO2 from 81 +/- 3 to 49 +/- 8%. In contrast, in the presence of hypothermia, MUHbO2 was significantly higher during hemorrhagic shock (from 79 +/ 3 to 66 +/- 9%) despite a similar decrease in DO2. The effect of hypothermia on MUHbO2 was reduced in the presence of thoracic epidural anesthesia or vasopressin receptor blockade. CONCLUSIONS: Hypothermia preserves MUHbO2 during hemorrhagic shock. This effect is partially abolished during thoracic epidural anesthesia or during vasopressin receptor blockade. The sympathetic nervous system and the vasopressin V1 receptor are partially involved in mediating the effect of hypothermia on gastric oxygenation during hemorrhage. PMID- 26905214 TI - Bullous fixed drug eruption in a patient with metastatic renal cell carcinoma induced by iodinated contrast during pazopanib treatment. PMID- 26905215 TI - Effects of steroid treatment on growth, nutrient partitioning, and expression of genes related to growth and nutrient metabolism in adult triploid rainbow trout (Oncorhynchus mykiss). AB - The contribution of sex steroids to nutrient partitioning and energy balance during gonad development was studied in rainbow trout. Specifically, 19-mo old triploid (3N) female rainbow trout were fed treatment diets supplemented with estradiol-17beta (E2), testosterone (T), or dihydrotestosterone at 30-mg steroid/kg diet for a 1-mo period. Growth performance, nutrient partitioning, and expression of genes central to growth and nutrient metabolism were compared with 3N and age-matched diploid (2N) female fish consuming a control diet not supplemented with steroids. Only 2 N fish exhibited active gonad development, with gonad weights increasing from 3.7% to 5.5% of body weight throughout the study, whereas gonad weights in 3N fish remained at 0.03%. Triploid fish consuming dihydrotestosterone exhibited faster specific growth rates than 3N controls (P < 0.05). Consumption of E2 in 3N fish reduced fillet growth and caused lower fillet yield compared with all other treatment groups (P < 0.05). In contrast, viscera fat gain was not affected by steroid consumption (P > 0.05). Gene transcripts associated with physiological pathways were identified in maturing 2N and E2-treated 3N fish that differed in abundance from 3N-control fish (P < 0.05). In liver these mechanisms included the growth hormone/insulin like growth factor (IGF) axis (igf1, igf2), IGF binding proteins (igfbp1b1, igfbp2b1, igfbp5b1, igfbp6b1), and genes associated with lipid binding and transport (fabp3, fabp4, lpl, cd36), fatty acid oxidation (cpt1a), and the pparg transcription factor. In muscle, these mechanisms included reductions in myogenic gene expression (fst, myog) and the proteolysis-related gene, cathepsin-L, suggesting an E2-induced reduction in the capacity for muscle growth. These findings suggest that increased E2 signaling in the sexually maturing female rainbow trout alters physiological pathways in liver, particularly those related to IGF signaling and lipid metabolism, to partition nutrients away from muscle growth toward support of maturation-related processes. In contrast, the mobilization of viscera lipid stores appear to be mediated less by E2 and more by energy demands associated with gonad development. These findings improve the understanding of how steroids regulate nutrient metabolism to meet the high energy demands associated with gonad development during sexual maturation. PMID- 26905218 TI - Erratum to: Limited role of culture conversion for decision-making in individual patient care and for advancing novel regimens to confirmatory clinical trials. PMID- 26905217 TI - Functionalization of poly(epsilon-caprolactone) surface with lactose-modified chitosan via alkaline hydrolysis: ToF-SIMS characterization. AB - Functionalization of poly(epsilon-caprolactone) (PCL) was performed via hydrolysis and subsequent grafting of lactose-modified chitosan (chitlac) at two different degrees of derivatization (9% and 64%). Time of flight secondary ion mass spectrometry (ToF-SIMS) and multivariate analysis (principal component analysis) were successfully applied to the characterization of PCL surface chemistry, evidencing changes in the biopolymer surface following base-catalyzed hydrolysis treatment. ToF-SIMS analysis also confirmed positive EDC/NHS-catalyzed (EDC: N-ethyl-N'-(3-(dimethylamino)propyl)carbodiimide; NHS: N hydroxysuccinimide) immobilization of chitlac onto activated PCL surface, with formation of amide bonds between PCL surface carboxyl groups and amine residues of chitlac. Yield of grafting reaction was also shown to be dependent upon the lactosilation degree of chitlac. PMID- 26905216 TI - Effects of the Microparticle Shape on Cellular Uptake. AB - Physical forms of microparticles and nanoparticles, such as the size, charge, and shape, are known to affect endocytosis. Improving the physical designs of the drug carriers can increase the drug uptake efficiency and the subsequent drug efficacy. Simple shapes, such as sphere and cylinder, have been studied for their ability for endocytosis. To have a better understanding of the shape effect on cellular uptake, different particle shapes were prepared, using the keyboard character shapes, and their impacts on cellular uptake were examined. The results showed that shapes with higher aspect ratios and sharper angular features have a higher chance of adhering to the cells and become internalized by the cancer cells. The local interaction between the cell membrane and the part of the microparticle in contact with the cell membrane also plays a crucial role in determining the outcome. PMID- 26905219 TI - Room-Temperature Chemical Solution Treatment for Flexible ZnS(O,OH)/Cu(In,Ga)Se2 Solar Cell: Improvements in Interface Properties and Metastability. AB - We demonstrate an effective room-temperature chemical solution treatment, by using thioacetamide (S treatment) or thioacetamide-InCl3 (In-S treatment) solution, on Cu(In,Ga)Se2 (CIGSe) surface to engineer the ZnS(O,OH)/CIGSe interface and junction quality, leading to enhanced efficiency and minimized metastability of flexible solar cells. The control device without treatment reveals a relatively low efficiency of 8.15%, which is significantly improved to 9.74% by In-S treatment, and 10.39% by S treatment. Results of X-ray photoelectron spectroscopy suggest that S is incorporated into CIGSe surface forming CIGSSe by S treatment, whereas a thin In-S layer is formed on CIGSe surface by In-S treatment with reduced amount of S diffusing into CIGSe. PL spectra and TRPL lifetime further reveal that S incorporation into CIGS surface may substitute the OSe and/or directly occupy the vacant anion site (VSe), resulting in the effective passivation of the recombination centers at CIGSe surface. Moreover, reducing the concentrations of VSe may thereby decrease the density of (VCu-VSe) acceptors, which can minimize the metastability of ZnS(O,OH)/CIGSe solar cells. With S treatment, the light soaking (LS) time of ZnS(O,OH)/CIGSe device is reduced approximately to one-half of control one. Our approach can be potentially applied for alternative Cd-free buffer layers to achieve high efficiency and low metastability. PMID- 26905220 TI - Can BNP-guided therapy improve health-related quality of life, and do responders to BNP-guided heart failure treatment have improved health-related quality of life? Results from the UPSTEP study. AB - BACKGROUND: To investigate whether B-type natriuretic peptide (NP)-guided treatment of heart failure (HF) patients improved their health related quality of life (Hr-QoL) compared to routine HF treatment, and whether changes in Hr-QoL differed depending on whether the patient was a responder to NP-guided therapy or not. METHODS: A secondary analysis of the UPSTEP-study, a Scandinavian multicentre study using a prospective, randomized, open, blinded evaluation design on patients with HF with New York Heart Association (NYHA) class II-IV. NP guiding was aimed to reduce BNP <150 ng/L if < 75 years or BNP < 300 ng/L if > 75 years. A responder was defined as a patient with a BNP < 300 ng/L and/or a decrease in BNP of at least 40% in week 16 compared to study start. Short form-36 (SF-36) was used to measure Hr-QoL. At the study start, 258 patients presented evaluable SF-36 questionnaires, 131 in the BNP group and 127 in the control group. At the study end 100 patients in the NP-guided group and 98 in the control group, presenting data from both the study start and the study end. RESULTS: There were no significant differences in Hr-QoL between NP-guided HF treatment and control group; however significant improvements could be seen in four of the eight domains in the NP-guided group, whereas in the control group improvements could be seen in six of the domains. Among the responders improvements could be noted in four domains whereas in the non-responders improvements could be seen in only one domain evaluating within group changes. CONCLUSIONS: Improved Hr-QoL could be demonstrated in several of the domains in both the NP-guided and the control group. In the responder group within group analyses showed more increased Hr-QoL compared to the non-responder group. However, all groups demonstrated increase in Hr-QoL. PMID- 26905221 TI - Repositioning Bevacizumab: A Promising Therapeutic Strategy for Cartilage Regeneration. AB - Drug discovery and development has been garnering an increasing trend of research due to the growing incidence of the diverse types of diseases. Recently, drug repositioning, also known as drug repurposing, has been emerging parallel to cancer and tissue engineering studies. Drug repositioning involves the application of currently approved or even abandoned drugs as alternative treatments to other diseases or as biomaterials in other fields including cell therapy and tissue engineering. In this review, the advancement of the antiangiogenesis drugs that were used as treatment for cancer and other diseases, with particular focus on bevacizumab, will be described. This will include an overview of the nature and progression of osteoarthritis (OA), one of the leading global degenerative diseases that cause morbidity, and the development of its therapeutic strategies. In addition, this will also feature the nonsteroidal anti inflammatory drugs that are commonly prescribed for OA and the benefits of repositioning bevacizumab as alternative treatments for other diseases and as biomaterials for cartilage regeneration. To date, a few number of studies, employing different modes of administration and varying dosages in diverse animal models, have shown that bevacizumab can be used as a signal and can promote both in vitro and in vivo cartilage regeneration. However, other antiangiogenesis drugs and their effects in chondrogenesis and cartilage regeneration are also worth investigating. PMID- 26905222 TI - Enabling relationship formation, development, and closure in a one-year female mentoring program at a non-governmental organization: a mixed-method study. AB - BACKGROUND: Mental health problems among young women aged 16-24 have increased significantly in recent decades, and interventions are called for. Mentoring is a well-established preventative/promotive intervention for developing adolescents, but we have yet to fully understand how the relationship between the mentor and the protege forms, develops, and closes. In this study, we focused on a female mentoring program implemented by a Swedish non-governmental organization, The Girls Zone. First, we examined the psychological and social characteristics of the young women who chose to take part in the program as proteges. Second, we investigated adolescent female proteges' own experiences of the relationship process based on a relational-cultural theory perspective. METHODS: The mixed method study included 52 questionnaires and five semi-structured interviews with young women aged 15-26 who had contacted The Girls Zone between 2010 and 2012 in order to find a mentor. Their experience of the mentoring relationships varied in duration. Data were analysed statistically and with inductive qualitative content analysis. RESULTS: The group of proteges was heterogeneous in that some had poor mental health and some had good mental health. On the other hand, the group was homogenous in that all its members had shown pro-active self-care by actively seeking out the program due to experiences of loneliness and a need to meet and talk with a person who could listen to them. The relationships were initially characterized by feelings of nervousness and ambivalence. However, after some time, these developed into authentic, undemanding, non-hierarchical relationships on the proteges' terms. The closure of relationships aroused feelings of both abandonment and developing strength. CONCLUSIONS: Mentorships that are in line with perspectives of the relational-cultural theory meet the relationship needs expressed by the female proteges. Mentor training should focus on promoting skills such as active listening and respect for the protege based on an engaged, empathic, and authentic approach in a non-hierarchical relationship. These insights have the potential to inform interventions in several arenas where young women create authentic relationships with older persons, such as in school, in traditional health care contexts, and in youth recreation centres. PMID- 26905223 TI - Erratum. PMID- 26905224 TI - Safety and cardiovascular effects of mineralocorticoid receptor antagonists for patients receiving hemodialysis: a systematic review and meta-analysis. AB - INTRODUCTION: Cardiovascular disease is an important factor in the mortality and morbidity of patients with end-stage renal disease receiving hemodialysis. Although mineralocorticoid receptor antagonists may have potential benefits on the cardiovascular system, their safety for patients on hemodialysis remains unclear, considering the differences between the results of already performed clinical trials. METHODS: MEDLINE, EMBASE, Cochrane, ClinicalTrials.gov and PubMed databases were searched for relevant clinical trials. The Cochrane Collaboration assessment tool was employed to evaluate the quality of the randomized controlled trials. Revman 5.3 was used to perform the meta-analysis. RESULTS: Eleven studies (n=379) were included in the systematic review and five randomized controlled trials were included in the meta-analysis (n=248). Mineralocorticoid antagonists (MRAs) did not increase predialysis potassium levels significantly (0.11, 95% confidence interval -0.03 to 0.25, p = 0.11). However, the studies included in this review reported inconsistently with respect to effects of mineralocorticoid receptor antagonists on blood pressure, left ventricular ejection fraction and left ventricular hypertrophy, and quantitative analysis was not performed due to insufficient data. One trial showed that the mineralocorticoid receptor antagonists were associated with decreased carotid intima-media thickness and other articles concluded that mineralocorticoid receptor antagonists had no effect on aortic stiffness. CONCLUSION: It is safe to use low dose mineralocorticoid receptor antagonists on patients receiving hemodialysis, at the end of each session of hemodialysis, and close monitoring of serum potassium levels and possible side effects is necessary. The cardiovascular actions still need to be explored and large scale RCTs are in progress. PMID- 26905226 TI - A niobium-necked cluster [As3Nb(As3Sn3)](3-) with aromatic Sn3(2-) . AB - We describe here the synthesis and characterization of a ternary cluster compound [As3Nb(As3Sn3)](3-) (1), in which a niobium(v) atom is coordinated by an As3(3-) triangle and a bowl-type As3Sn3(5-) ligand. Cluster 1 was synthesized by dissolving K8NbSnAs5 (2) in the presence of [2.2.2]crypt in ethylenediamine solution, filtered and layered with toluene, then crystallized in the form of [K([2.2.2]crypt)]3[As3Nb(As3Sn3)].en.tol. The flower-vase shaped compound 1 features a new structure type, rather different from the known Zintl phases. The stability and bonding of 1 are elucidated via extensive bonding analyses. The Sn3 ring is found to have sigma-aromaticity featuring a delocalized Sn-Sn-Sn sigma bond. Electronic structure calculations confirm the Nb(v) oxidation state and weak Nb-Sn and Sn-Sn bonding, in addition to the normal Nb-As and As-As bonds. PMID- 26905227 TI - Anti-inflammatory Actions of (+)-3'alpha-Angeloxy-4'-keto-3',4'-dihydroseselin (Pd-Ib) against Dextran Sulfate Sodium-Induced Colitis in C57BL/6 Mice. AB - The immunoregulatory protective properties of (+)-3'alpha-angeloxy-4'-keto-3',4' dihydroseselin (Pd-Ib) isolated from Bupleurum malconense has not been reported. In the present study, the therapeutic effect of Pd-Ib (30, 60, and 120 mg/kg/day) was examined in a mouse model of dextran sulfate sodium (DSS)-induced acute colitis. Administration of Pd-Ib significantly reduced the disease activity index, inhibited the shortening of colon length, reduced colonic tissue damage, and suppressed colonic myeloperoxidase activity and nitric oxide levels in mice with DSS-induced colitis. Moreover, Pd-Ib greatly suppressed the secretion of pro inflammatory cytokines TNF-alpha, IFN-gamma, IL-6, and IL-17A while enhancing the level of anti-inflammatory cytokine IL-4. The protein levels of phosphorylated STAT3 (p-STAT3) and phosphorylated p38 (p-p38) were down-regulated in the colonic tissues of DSS-treated mice. Importantly, the anti-inflammatory effect of Pd-Ib against acute colitis was comparable to the anti-inflammatory sulfa drug sulfasalazine (300 mg/kg). Furthermore, the in vitro study showed that the inhibitory effect of Pd-Ib on p-STAT3 and IL-6 protein levels was accompanied by the reduction of MAPKs (JNK and p38). In conclusion, this study suggested that Pd Ib attenuated DSS-induced acute colitis via the regulation of interleukins principally through the STAT3 and MAPK pathways. PMID- 26905228 TI - Psychometric properties of the Positive and Negative Affect Schedule (PANAS) in a heterogeneous sample of substance users. AB - BACKGROUND: The Positive and Negative Affect Schedule (PANAS) is a widely used measure of affect. A comprehensive psychometric evaluation among substance users, however, has not been published. OBJECTIVE: To examine the psychometric properties of the PANAS in a sample of outpatient treatment substance users. METHODS: We used pooled data from four randomized clinical trials (N = 416; 34% female, 48% African American). RESULTS: A confirmatory factor analysis indicated adequate support for a two-factor correlated model comprised of Positive Affect and Negative Affect with correlated item errors (Comparative Fit Index = 0.93, Root Mean Square Error of Approximation = 0.07, chi(2) = 478.93, df = 156). Cronbach's alpha indicated excellent internal consistency for both factors (0.90 and 0.91, respectively). The PANAS factors had good convergence and discriminability (Composite Reliability > 0.7; Maximum Shared Variance < Average Variance Extracted). A comparison from baseline to Week 1 indicated acceptable test-retest reliability (Positive Affect = 0.80, Negative Affect = 0.76). Concurrent and discriminant validity were demonstrated with correlations with the Brief Symptom Inventory and Addiction Severity Index. The PANAS scores were also significantly correlated with treatment outcomes (e.g. Positive Affect was associated with the maximum days of consecutive abstinence from primary substance of abuse, r = 0.16, p = 0.001). CONCLUSION: Our data suggest that the psychometric properties of the PANAS are retained in substance using populations. Although several studies have focused on the role of Negative Affect, our findings suggest that Positive Affect may also be an important factor in substance use treatment outcomes. PMID- 26905229 TI - Pylorus-preserving pancreaticoduodenectomy (pp Whipple) versus pancreaticoduodenectomy (classic Whipple) for surgical treatment of periampullary and pancreatic carcinoma. AB - BACKGROUND: Pancreatic cancer is the fourth-leading cause of cancer death for both, men and women. The standard treatment for resectable tumours consists of a classic Whipple (CW) operation or a pylorus-preserving pancreaticoduodenectomy (PPW). It is unclear which of these procedures is more favourable in terms of survival, postoperative mortality, complications, and quality of life. OBJECTIVES: The objective of this systematic review was to compare the effectiveness of CW and PPW techniques for surgical treatment of cancer of the pancreatic head and the periampullary region. SEARCH METHODS: We conducted searches on 28 March 2006, 11 January 2011, 9 January 2014, and 18 August 2015 to identify all randomised controlled trials (RCTs), while applying no language restrictions. We searched the following electronic databases on 18 August 2015: the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Database of Systematic Reviews (CDSR) and the Database of Abstracts of Reviews of Effects (DARE) from the Cochrane Library (2015, Issue 8); MEDLINE (1946 to August 2015); and EMBASE (1980 to August 2015). We also searched abstracts from Digestive Disease Week and United European Gastroenterology Week (1995 to 2010); we did not update this part of the search for the 2014 and 2015 updates because the prior searches did not contribute any additional information. We identified two additional trials through the updated search in 2015. SELECTION CRITERIA: RCTs comparing CW versus PPW including participants with periampullary or pancreatic carcinoma. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from the included trials. We used a random-effects model for pooling data. We compared binary outcomes using odds ratios (ORs), pooled continuous outcomes using mean differences (MDs), and used hazard ratios (HRs) for meta-analysis of survival. Two review authors independently evaluated the methodological quality and risk of bias of included trials according to the standards of The Cochrane Collaboration. MAIN RESULTS: We included eight RCTs with a total of 512 participants. Our critical appraisal revealed vast heterogeneity with respect to methodological quality and outcome parameters. Postoperative mortality (OR 0.64, 95% confidence interval (CI) 0.26 to 1.54; P = 0.32), overall survival (HR 0.84, 95% CI 0.61 to 1.16; P = 0.29), and morbidity showed no significant differences, except of delayed gastric emptying, which significantly favoured CW (OR 3.03, 95% CI 1.05 to 8.70; P = 0.04). Furthermore, we noted that operating time (MD -45.22 minutes, 95% CI -74.67 to -15.78; P = 0.003), intraoperative blood loss (MD -0.32 L, 95% CI -0.62 to -0.03; P = 0.03), and red blood cell transfusion (MD -0.47 units, 95% CI -0.86 to -0.07; P = 0.02) were significantly reduced in the PPW group. All significant results were associated with low-quality evidence based on GRADE (Grades of Recommendation, Assessment, Development and Evaluation) criteria. AUTHORS' CONCLUSIONS: Current evidence suggests no relevant differences in mortality, morbidity, and survival between the two operations. However, some perioperative outcome measures significantly favour the PPW procedure. Given obvious clinical and methodological heterogeneity, future high-quality RCTs of complex surgical interventions based on well-defined outcome parameters are required. PMID- 26905230 TI - Yttrium-90 microsphere radioembolisation for unresectable hepatocellular carcinoma. AB - BACKGROUND: Hepatocellular carcinoma is the most common liver neoplasm and the fifth most common cancer worldwide. Moreover, its incidence has increased dramatically since the mid-2000s. While surgical resection and liver transplantation are the main curative treatments, only around 20% of people with early hepatocellular carcinoma may benefit from these therapies. Current treatment options for unresectable hepatocellular carcinoma include various ablative and trans-arterial therapies in addition to the drug sorafenib. OBJECTIVES: To determine the benefits and harms of yttrium-90 microsphere trans arterial radioembolisation either as a monotherapy or in combination with other systemic or locoregional therapies versus placebo, no treatment, or other similar systemic or locoregional therapies for people with unresectable hepatocellular carcinoma. SEARCH METHODS: We reviewed data from the Cochrane Hepato-Biliary Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and Science Citation Index Expanded. We also checked reference lists of primary original studies and review articles manually for further related articles (cross-references) up to December 2015. SELECTION CRITERIA: Eligible studies included all randomised clinical trials comparing yttrium-90-90 microsphere radioembolisation either as a monotherapy or in combination with other systemic or locoregional therapies versus placebo, no treatment, or other systemic or locoregional therapies for unresectable hepatocellular carcinoma. DATA COLLECTION AND ANALYSIS: The two review authors independently extracted the relevant information on participant characteristics, interventions, study outcomes, and data on the outcomes for this review, as well as information on the design and methodology of the studies. The two review authors assessed risk of bias of the included trials using pre-defined risk of bias domains. We used Trial Sequential Analysis to control the risk of random errors. We assessed the methodological quality with GRADE. MAIN RESULTS: Two randomised clinical trials with 68 participants fulfilled our inclusion criteria. Both trials were at high risk of bias, and we rated the evidence as very low quality. One of the included trials compared radioembolisation versus chemoembolization for intermediate stage hepatocellular carcinoma as classified by the Barcelona Clinic Liver Cancer (BCLC) staging system, while the other included trial was an interim analysis of a randomised trial assessing radioembolisation combined with sorafenib versus sorafenib monotherapy in participants with BCLC-advanced stage hepatocellular carcinoma. The available data were insufficient to perform the planned analyses. Neither of the two trials reported data on all-cause mortality, cancer-related mortality, or time to progression of the tumour. The trial comparing radioembolisation with chemoembolization reported quality of life and serious adverse events, and there were no statistically significant differences between the trial groups with regard to these outcomes at week 12. On the basis of the two included randomised clinical trials, single-session radioembolisation appeared to be as safe as multiple sessions of chemoembolization for intermediate stage hepatocellular carcinoma and had a similar impact on quality of life, but data were too sparse to exclude even major differences. Radioembolisation followed by sorafenib appeared to be as well tolerated as sorafenib alone for advanced stage hepatocellular carcinoma, but data were too sparse to exclude even major differences. We also identified five ongoing studies evaluating the topic of our review. AUTHORS' CONCLUSIONS: There was insufficient evidence to assess the beneficial and harmful effects of yttrium-90 microsphere radioembolisation for people with unresectable hepatocellular carcinoma. Further randomised clinical trials are mandatory to better assess the potential beneficial and harmful outcomes of yttrium-90 microsphere trans-arterial radioembolisation either as a monotherapy or in combination with other systemic or locoregional therapies versus placebo, no treatment, or other systemic or locoregional therapies for people with unresectable hepatocellular carcinoma. PMID- 26905232 TI - Trapping molecular bromine: a one-dimensional bromobismuthate complex with Br2 as a linker. AB - The reaction between solid (NMP)n{[BiBr4]}n (1) (NMP = N-methylpyridinium) and Br2, generated in situ in HBr solution, results in the formation of (NMP)3[Bi2Br9].Br2 (2). In the structure of 2, dibromine molecules connect discrete binuclear [Bi2Br9](3-) anions into an extended network. Complex 2 is thermally stable (up to 150 degrees C). PMID- 26905231 TI - Temporal properties of network-mediated responses to repetitive stimuli are dependent upon retinal ganglion cell type. AB - OBJECTIVE: To provide artificially-elicited vision that is temporally dynamic, retinal prosthetic devices will need to repeatedly stimulate retinal neurons. However, given the diversity of physiological types of retinal ganglion cells (RGCs) as well as the heterogeneity of their responses to electric stimulation, temporal properties of RGC responses have not been adequately investigated. Here, we explored the cell type dependence of network-mediated RGC responses to repetitive electric stimulation at various stimulation rates. APPROACH: We examined responses of ON and OFF types of RGCs in the rabbit retinal explant to five consecutive stimuli with varying inter-stimulus intervals (10-1000 ms). Each stimulus was a 4 ms long monophasic sinusoidal cathodal current, which was applied epiretinally via a conical electrode. Spiking activity of targeted RGCs was recorded using a cell-attached patch electrode. MAIN RESULTS: ON and OFF cells had distinct responses to repetitive stimuli. Consistent with earlier studies, OFF cells always generated reduced responses to subsequent stimuli compared to responses to the first stimulus. In contrast, a new stimulus to ON cells suppressed all pending/ongoing responses from previous stimuli and initiated its own response that was remarkably similar to the response from a single stimulus in isolation. This previously unreported 'reset' behavior was observed exclusively and consistently in ON cells. These contrasts between ON and OFF cells created a range of stimulation rates (4-7 Hz) that maximized the ratio of the responses arising in ON versus OFF cells. SIGNIFICANCE: Previous clinical testing reported that subjects perceive bright phosphenes (ON responses) and also prefer stimulation rates of 5-7 Hz. Our results suggest that responses of ON cells are weak at high rates of stimulation (> ~7 Hz) due to the reset while responses of OFF cells are strong at low rates (< ~4 Hz) due to reduced desensitization, both reducing the ratio of ON to OFF responses. In combination with previous results indicating that responses in ON cells more closely match physiological patterns (Im and Fried 2015 J. Physiol. 593 3577-96), our results offer a potential reason for the user preference of intermediate rates (5-7 Hz). PMID- 26905233 TI - Re-emergence of dengue virus serotype 2 strains in the 2013 outbreak in Nepal. AB - BACKGROUND & OBJECTIVES: Epidemiological interventions and mosquito control are the available measures for dengue control. The former approach uses serotype and genetic information on the circulating virus strains. Dengue has been frequently reported from Nepal, but this information is mostly lacking. The present study was done to generate a comprehensive clinical and virological picture of a dengue outbreak in Nepal during 2013. METHODS: A hospital-based study involving patients from five districts of Nepal was carried out. Demographic information, clinical details and dengue serological status were obtained. Viral RNA was characterized at the molecular level by reverse-transcription polymerase chain reaction (RT PCR), nucleotide sequencing and phylogenetic analysis. RESULTS: From among the 2340 laboratory-confirmed dengue cases during the study period, 198 patients consented for the study. Clinically they had fever (100%), headache (59.1%), rashes (18.2%), retro-orbital pain (30.3%), vomiting (15.1%), joint pain (28.8%) and thrombocytopenia (74.3%). Fifteen (7.5%) of them had mucosal bleeding manifestations, and the rest were uncomplicated dengue fever. The patients were mostly adults with a mean age of 45.75 +/- 38.61 yr. Of the 52 acute serum samples tested, 15 were positive in RT-PCR. The causative virus was identified as DENV serotype 2 belonging to the Cosmopolitan genotype. INTERPRETATIONS & CONCLUSIONS: We report here the involvement of DENV serotype 2 in an outbreak in Nepal in 2013. Earlier outbreaks in the region in 2010 were attributed to serotype 1 virus. As serotype shifts are frequently associated with secondary infections and severe disease, there is a need for enhancing surveillance especially in the monsoon and post-monsoon periods to prevent large-scale, severe dengue outbreaks in the region. PMID- 26905234 TI - Antimalarial efficacy of Albizia lebbeck (Leguminosae) against Plasmodium falciparum in vitro & P. berghei in vivo. AB - BACKGROUND & OBJECTIVES: Albizia lebbeck Benth. (Leguminosae) has long been used in Indian traditional medicine. The current study was designed to test antimalarial activity of ethanolic bark extract of A. lebbeck (EBEAL). METHODS: EBEAL was prepared by soxhlet extraction and subjected to phytochemical analysis. The extract was evaluated for its in vitro antimalarial activity against Plasmodium falciparum chloroquine (CQ) sensitive (MRC2) and CQ resistant (RKL9) strains. Cytotoxicity (CC 50 ) of extract against HeLa cells was evaluated. Median lethal dose (LD 50 ) was determined to assess safety of EBEAL in BALB/c mice. Schizonticidal (100-1000 mg/kg) and preventive (100-750 mg/kg) activities of EBEAL were evaluated against P. berghei. Curative activity (100-750 mg/kg) of extract was also evaluated. RESULTS: Phytochemical screening revealed presence of alkaloids, flavonoids, phenols, saponins, terpenes and phytosterols. The extract exhibited IC 50 of 8.2 ug/ml (MRC2) and 5.1 ug/ml (RKL9). CC 50 of extract on HeLa cell line was calculated to be >1000 ug/ml. EBEAL showed selectivity indices (SI) of >121.9 and >196.07 against MRC2 and RKL9 strains of P. falciparum, respectively. LD 50 of EBEAL was observed to be >5 g/kg. Dose-dependent chemosuppression was observed with significant ( p<0.001) schizonticidal activity at 1000 mg/kg with ED 50 >100 mg/kg. Significant (P<0.001) curative and repository activities were exhibited by 750 mg/kg concentration of extract on D7. INTERPRETATION & CONCLUSIONS: The present investigation reports antiplasmodial efficacy of EBEAL in vitro against P. falciparum as evident by high SI values. ED 50 of <100 mg/kg against P. berghei categorizes EBEAL as active antimalarial. Further studies need to be done to exploit its antiplasmodial activity further. PMID- 26905235 TI - Chikungunya outbreak in Atmakur village, Medak district, Telangana State, India. PMID- 26905236 TI - Chikungunya fever outbreak in Guntur, Andhra Pradesh, India. PMID- 26905237 TI - Malaria transmission in Tripura: Disease distribution & determinants. AB - BACKGROUND & OBJECTIVES: Malaria is a major public health problem in Tripura and focal disease outbreaks are of frequent occurrence. The state is co-endemic for both Plasmodium falciparum and P. vivax and transmission is perennial and persistent. The present study was aimed to review data on disease distribution to prioritize high-risk districts, and to study seasonal prevalence of disease vectors and their bionomical characteristics to help formulate vector species specific interventions for malaria control. METHODS: Data on malaria morbidity in the State were reviewed retrospectively (2008-2012) for understanding disease distribution and transmission dynamics. Cross-sectional mass blood surveys were conducted in malaria endemic villages of South Tripura district to ascertain the prevalence of malaria and proportions of parasite species. Mosquito collections were made in human dwellings of malaria endemic villages aiming at vector incrimination and to study relative abundance, resting and feeding preferences, and their present susceptibility status to DDT. RESULTS: The study showed that malaria was widely prevalent and P. falciparum was the predominant infection (>90%), the remaining were P. vivax cases. The disease distribution, however, was uneven with large concentration of cases in districts of South Tripura and Dhalai coinciding with vast forest cover and tribal populations. Both Anopheles minimus s.s. and An. baimaii were recorded to be prevalent and observed to be highly anthropophagic and susceptible to DDT. Of these, An. minimus was incriminated (sporozoite infection rate 4.92%), and its bionomical characteristics revealed this species to be largely indoor resting and endophagic. INTERPRETATION & CONCLUSIONS: For effective control of malaria in the state, it is recommended that diseases surveillance should be robust, and vector control interventions including DDT spray coverage, mass distribution of insecticide-treated nets/ long lasting insecticidal nets should be intensified prioritizing population groups most at risk to avert impending disease outbreaks and spread of drug-resistant malaria. PMID- 26905238 TI - Seasonal abundance & role of predominant Japanese encephalitis vectors Culex tritaeniorhynchus & Cx. gelidus Theobald in Cuddalore district, Tamil Nadu. AB - BACKGROUND & OBJECTIVES: Japanese encephalitis (JE) is the leading cause of viral encephalitis in Asia. The first major JE outbreak occurred in 1978 and since 1981 several outbreaks had been reported in the Cuddalore district (erstwhile South Arcot), Tamil Nadu, India. Entomological monitoring was carried out during January 2010 - March 2013, to determine the seasonal abundance and transmission dynamics of the vectors of JE virus, with emphasis on the role of Culex tritaeniorhynchus and Cx. gelidus. METHODS: Mosquito collections were carried out fortnightly during dusk hours in three villages viz. Soundara Solapuram, Pennadam, Erappavur of Cuddalore district. Mosquitoes were collected during dusk for a period of one hour in and around the cattle sheds using oral aspirator and torch light. The collected mosquitoes were later identified and pooled to detect JE virus (JEV) infection by enzyme linked immunosorbent assay (ELISA). RESULTS: A total of 46,343 mosquitoes comprising of 25 species and six genera were collected. Species composition included viz, Cx. tritaeniorhynchus (46.26%), Cx. gelidus (43.12%) and other species (10.62%). A total of 17,678 specimens (403 pools) of Cx. gelidus and 14,358 specimens (309 pools) of Cx. tritaeniorhynchus were tested, of which 12 pools of Cx. gelidus and 14 pools of Cx. tritaeniorhynchus were positive for JE virus antigen. The climatic factors were negatively correlated with minimum infection rate (MIR) for both the species, except mean temperature (P<0.05) for Cx. gelidus. INTERPRETATION & CONCLUSIONS: High abundance of Cx. tritaeniorhynchus and Cx. gelidus was observed compared to other mosquito species in the study area. Detection of JEV antigen in the two species confirmed the maintenance of virus. Appropriate vector control measures need to be taken to reduce the vector abundance. PMID- 26905239 TI - An outbreak of Japanese encephalitis after two decades in Odisha, India. AB - Sudden deaths in children due to acute encephalitis syndrome (AES) from a tribal dominated district of Malkangiri in Odisha, India, was reported during September November, 2012. The investigation was carried out to search for the possible viral aetiology that caused this outbreak. Clinico-epidemiological survey and seromolecular investigation were carried out to confirm the viral aetiology. Two hundred seventy two suspected cases with 24 deaths were observed. The patients presented with low to moderate grade fever (87%), headache (43%), vomiting (27%), cold (18%), cough (17%), body ache (15%), joint pain (15%), rash (15%), abdomen pain (9%), lethargy (5%), altered sensorium (8%), convulsion (2%), diarrhoea (3%), and haematemesis (3%). Laboratory investigation showed Japanese encephalitis virus (JEV) IgM in 13.8 per cent (13/94) in blood samples and JEV RNA in one of two cerebrospinal fluid (CSF) samples. Paddy fields close to the houses, high pig to cattle ratio, high density (33 per man hour density) of Culex vishnui mosquitoes, low socio-economic status and low health awareness in the tribal population were observed. This report confirmed the outbreak of JEV infection in Odisha after two decades. PMID- 26905240 TI - Chikungunya virus susceptibility & variation in populations of Aedes aegypti (Diptera: Culicidae) mosquito from India. AB - BACKGROUND & OBJECTIVES: Although having immense clinical relevance, yet only a few studies have been targeted to understand the chikungunya virus (CHIKV) susceptibility and growth in Aedes aegypti populations from India. This study was undertaken to investigate CHIKV susceptibility and growth kinetics in Ae. aegypti along with genetic heterogeneity of Ae. aegypti populations. METHODS: Dose dependent CHIKV susceptibility and growth kinetic studies for three CHIKV strains reported from India were carried out in Ae. aegypti mosquito populations. The phenotypic variation and genetic heterogeneity in five Ae. aegypti populations were investigated using multivariate morphometrics and allozyme variation studies. RESULTS: The dissemination and growth kinetics studies of the three CHIKV strains showed no selective advantage for a particular strain of CHIKV in Ae. aegypti. At 100 per cent infection rate, five geographic Ae. aegypti populations showed differences in dissemination to three CHIKV strains. Morphometric studies revealed phenotypic variation in all the studied populations. The allelic frequencies, F statistics, and Nei's genetic identity values showed that genetic differences between the populations were small, but significant. INTERPRETATION & CONCLUSIONS: The results obtained in this study suggest that genetic background of the vector strongly influences the CHIKV susceptibility in Ae. aegypti. PMID- 26905241 TI - Bagaza virus inhibits Japanese encephalitis & West Nile virus replication in Culex tritaeniorhynchus & Cx. quinquefasciatus mosquitoes. AB - BACKGROUND & OBJECTIVES: Studies have shown that certain flaviviruses influence susceptibility of mosquitoes by inhibiting/enhancing replication of important flaviviruses. Hence, a study was designed to determine whether Bagaza virus (BAGV), a flavivirus isolated from Culex tritaeniorhynchus mosquitoes in India, alters susceptibility of Cx. tritaeniorhynchus and Cx. quinquefasciatus mosquitoes to Japanese encephalitis (JEV) and West Nile viruses (WNV). METHODS: JEV and WNV infection in Cx. tritaeniorhynchus and Cx. quinquefasciatus mosquitoes in the presence of BAGV was carried out by intrathoracic (IT) inoculation and oral feeding methods. Mosquitoes were infected with BAGV and WNV/JEV either simultaneously or in a phased manner, in which mosquitoes were infected with BAGV by IT inoculation followed by super-infection with JEV/WNV after eight days post-infection (PI). JEV and WNV yield on 7 [th] and 14 [th] day PI after super-infection was determined by 50 per cent tissue culture infective dose (TCID 50 ) method. RESULTS: In Cx. tritaeniorhynchus mosquitoes, prior infection with BAGV significantly reduced JEV and WNV replication while in Cx. quinquefasciatus, BAGV influence was only seen with WNV. Reduction in virus titre was observed in IT inoculated and oral fed mosquitoes irrespective of the infection mode. JEV replication was also found reduced in Cx. tritaeniorhynchus mosquitoes persistently infected with BAGV at passage four. INTERPRETATION & CONCLUSIONS: BAGV infection in Cx. tritaeniorhynchus and Cx. quinquefasciatus mosquitoes altered their susceptibility to JEV and WNV producing low virus yield. However, the role of BAGV in inhibiting JEV/WNV replication in field mosquitoes needs further investigations. PMID- 26905242 TI - Field performance of malaria rapid diagnostic test for the detection of Plasmodium falciparum infection in Odisha State, India. AB - BACKGROUND & OBJECTIVES: Rapid diagnostic tests (RDTs) have become an essential surveillance tool in the malaria control programme in India. The current study aimed to assess the performance of ParaHIT-f, a rapid test in diagnosis of Plasmodium falciparum infection through detecting its specific antigen, histidine rich protein 2 (PfHRP-2), in Odisha State, India. METHODS: The study was undertaken in eight falciparum malaria endemic southern districts of Odisha State. Febrile patients included through active case detection, were diagnosed by Accredited Social Health Activists (ASHAs) for P. falciparum infection using the RDT, ParaHIT-f. The performance of ParaHIT-f was evaluated using microscopy as the gold standard. RESULTS: A total of 1030 febrile patients were screened by both microscopy and the RDT for P. falciparum infection. The sensitivity of ParaHIT-f was 63.6% (95% CI: 56.0-70.6) and specificity was 98.9% (95% CI: 97.9 99.5), with positive and negative predictive values (PPV and NPV) of 92.6% (95% CI: 86.0-96.3) and 93.0% (95% CI: 91.0-94.5), respectively. When related to parasitaemia, the RDT sensitivity was 47.8% at the low parasitaemia of 4 to 40 parasites/ul of blood. INTERPRETATION & CONCLUSIONS: The results showed that the performance of the RDT, ParaHIT-f, was not as sensitive as microscopy in detecting true falciparum infections; a high specificity presented a low frequency of false-positive RDT results. t0 he sensitivity of ParaHIT-f was around 60 per cent. It is, therefore, essential to improve the efficiency (sensitivity) of the kit so that the true falciparum infections will not be missed especially in areas where P. falciparum has been the predominant species causing cerebral malaria. PMID- 26905243 TI - Triple insecticide resistance in Anopheles culicifacies: A practical impediment for malaria control in Odisha State, India. AB - BACKGROUND & OBJECTIVES: In Odisha State, the control of malaria vectors has become dependent on synthetic pyrethroids, which are used for treatment of all approved long-lasting insecticidal nets (LLINs). The vast use of just one class of insecticide has led to the problem of resistance to insecticides in malaria vectors. One of the major malaria vectors in Odisha State is Anopheles culicifacies Giles. The aim of this study was to determine the resistance status of An. culicifacies to deltamethrin, a synthetic pyrethroid and other common insecticides used by the National Vector Borne Diseases Control Programme (NVBDCP) for indoor residual spraying in Odisha State. METHODS: Mosquitoes were collected during April 2014 - June 2014 from 15 randomly selected villages in five p0 lasmodium falciparum endemic southern districts of Odisha State. The blood-fed wild caught females were exposed to the diagnostic dosage of DDT (4.0%), malathion (5.0%) and deltamethrin (0.05%) for one hour. Mortality was recorded at 24 h after the exposure. RESULTS: Results indicated that An. culicifacies was resistant to all the three insecticides used in the malaria control programme in the five districts of Odisha State. INTERPRETATION & CONCLUSIONS: Resistance management strategy by appropriate rotation of different groups of insecticides including carbamates and incorporating a synergist with synthetic pyrethroids for treating mosquito nets should be considered for the control of malaria vectors in the area, especially where An. culicifacies is predominant. Periodical monitoring of susceptibility/resistance status of An. culicifacies to different insecticides is warranted. PMID- 26905244 TI - Adulticidal & larvicidal efficacy of three neonicotinoids against insecticide susceptible & resistant mosquito strains. AB - BACKGROUND & OBJECTIVES: Due to ever growing insecticide resistance in mosquitoes to commonly used insecticides in many parts of the globe, there is always a need for introduction of new insecticides for the control of resistant vector mosquitoes. In this study, larvicidal and adulticidal efficacies of three neonicotinoids (imidacloprid, thiacloprid and thiamethoxam) were tested against resistant and susceptible populations of Anopheles stephensi Liston 1901, Aedes (Stegomyia) aegypti Linnaeus, and Culex quinquefasciatus Say (Diptera: Culicidae). METHODS: Laboratory-reared mosquito species were used. Insecticide susceptibility tests were done using standard WHO procedures and using diagnostic dosages of insecticide test papers and larvicides. Adulticidal efficacy of candidate insecticides was assessed using topical application method and larval bioassays were conducted using standard WHO procedure. RESULTS: The results of topical application on 3-5 day old female mosquitoes indicated that resistant strain of An. stephensi registered lower LC 50 values than the susceptible strain. Among the three insecticides tested, thiacloprid was found more effective than the other two insecticides. Culex quinquefasciatus registered lowest LC 50 for imidacloprid than the other two mosquito species tested. In larval bioassays, the LC 50 values registered for imidacloprid were in the order of Cx. quinquefasciatus < An. stephensi (SS) < An. stephensi (RR) < Ae. aegypti. In case of thiacloprid, the order of efficacy (LC 50 ) was Cx. quinquefasciatus < An. stephensi (SS) < An. stephensi (RR), whereas in case of thiamethoxam, the larvicidal efficacy was in the order of An. stephensi (RR) < An. stephensi (SS) < Cx. quinquefasciatus. INTERPRETATION & CONCLUSIONS: The present study indicated that insecticide resistant strains of mosquito species tested showed more susceptibility to the three neonicotinoids tested, and the possibility of using neonicotinoids for the control of resistant mosquitoes should be explored. PMID- 26905245 TI - Observation on dengue cases from a virus diagnostic laboratory of a tertiary care hospital in North India. AB - BACKGROUND & OBJECTIVES: The epidemiology of dengue fever (DF) is complex in the Indian subcontinent as all the four serotypes are circulating. This study reports observations on dengue cases from a virus diagnostic laboratory of a north Indian tertiary care hospital catering to areas in and around Lucknow, Uttar Pradesh. METHODS: Serum samples were obtained from suspected cases of dengue referred to the virus diagnostic laboratory during 2011 to 2013, and detailed history was taken on a pre-structured datasheet. All samples were tested for anti-dengue virus (DV) IgM antibodies and DV-non structural protein 1 antigen (NS1Ag) by ELISA. NS1Ag positive samples were tested further by conventional RT-PCR for DV RNA detection and serotyping. RESULTS: Of the 4019 suspected patients of dengue, 886 (22%) showed laboratory evidence of dengue virus infection. Of these, 19, 17 and 27 per cent were positive in 2011, 2012 and 2013, respectively. Children and adults were similarly affected by dengue in all the three years. Males were more commonly affected than females. The predominant DV serotype detected was DV-2, DV 1 and DV-3 in 2011, 2012 and 2013, respectively. DV-4 serotype was not detected. About half the cases positive for DV infection, showed symptoms of dengue with warning signs/ severe dengue. A distinct seasonality with increase in number of dengue cases in the post monsoon period was seen. INTERPRETATION & CONCLUSIONS: Change in circulating serotype of dengue virus; a distinct adult dengue involvement; and a remarkable number of cases presenting with severe dengue manifestations are the main findings of this study. PMID- 26905246 TI - Usage pattern, physical integrity & insecticidal efficacy of long-lasting insecticidal nets in Odisha State, India. AB - BACKGROUND & OBJECTIVES: One of the major strategies being pursued for malaria control by the National Vector Borne Disease Control Programme is the distribution of long lasting insecticidal nets (LLINs) in endemic areas since 2009. Information on durability of insecticidal efficacy and physical integrity of LLINs and community usage at different time intervals of their use is essential to plan net replacements to maintain universal coverage for an effective and sustainable malaria control strategy. Therefore, a study was undertaken to assess these parameters in two malaria endemic districts of the Odisha State. METHODS: A total of 309 households were selected in 15 villages of two community health centres (CHCs) (Borigumma and Laxmipur) from Koraput district and one (Khairput) from Malkangiri district. Data on net usage were collected during March to July 2014 using semi-structured questionnaires. PermaNet 2.0 were sampled from all households, replaced with new ones, and bioassays were carried out to determine the insecticidal efficacy of LLINs after four and half, four and two years of field use following the standard procedure of World Health Organization. RESULTS: LLIN use rate varied from 57.9 to 90.2 per cent in the study CHCs. The annual washing rate per net in Borigumma, Khairput and Laxmipur was 6.6, 3.2 and 4.8, respectively. The LLINs used two years in the field caused 100 per cent mortality and four to four and half years caused below 80 per cent mortality, except one net. INTERPRETATION & CONCLUSIONS: Nearly 20 per cent of the people were out of net coverage and hence the Programme to ensure 100 per cent coverage. The community should adequately be educated so as to increase the net use rate and avoid incorrect washing practices. PMID- 26905247 TI - Spatial distribution & physicochemical characterization of the breeding habitats of Aedes aegypti in & around Kolkata, West Bengal, India. AB - BACKGROUND & OBJECTIVES: Dengue infection is endemic in several areas and the dengue virus is transmitted by Aedes mosquitoes. Thus, it becomes important to understand the breeding ecology of dengue vector and characterize the physicochemical parameters of its breeding habitat. The objective of this study was to analyze the physicochemical parameters of the breeding habitat of the dengue vector and to find out the nutrient composition of the habitat in and around Kolkata, West Bengal. In addition, a geographic information system (GIS) was used to map the disease prone areas for its effective management and prevention. METHODS: Water samples were collected from various breeding habitats of Aedes mosquitoes of Kolkata and adjoining areas and were analysed for various physicochemical properties like acidity, alkalinity, hardness, electrical conductivity, total dissolved solids, concentration of chloride (Cl - ), sodium (Na + ), potassium (K + ), fluoride (F - ) in relation to larval prevalence. RESULTS: Parameters like water pH, total dissolved solids, total hardness, electrical conductivity, concentration of chloride, sodium and potassium were seen to vary throughout the year. Certain parameters were found to be dependent on container type, like concentration of fluoride. Significant positive correlations were seen between per dip larval density and total dissolved solids (TDS) and electrical conductivity. INTERPRETATION & CONCLUSIONS: Water pH, electrical conductivity, total dissolved solids were seen to play a major role in the ovipositional preferences. Container type did not seem to affect TDS. Tyres had the highest TDS in most of the cases. Nutrient composition like sodium concentration was mostly found in the coconut shells, potassium concentration also showed the same. Thus, container type and various parameters and nutrients play a major role in determining where a gravid female mosquito will lay its eggs. It was observed that by altering various chemical and physical properties of breeding habitats it was possible to control the larvae survivability. PMID- 26905248 TI - Pupal productivity & nutrient reserves of Aedes mosquitoes breeding in sewage drains & other habitats of Kolkata, India: Implications for habitat expansion & vector management. AB - BACKGROUND & OBJECTIVES: The quality of breeding sites is reflected through the pupal productivity and the life history traits of Aedes mosquitoes. Using nutrient reserves and pupal productivity of Aedes as indicators, the larval habitats including sewage drains were characterized to highlight the habitat expansion and vector management. METHODS: The pupae and adults collected from the containers and sewage drains were characterized in terms of biomass and nutrient reserves and the data were subjected to three way factorial ANOVA. Discriminant function analyses were performed to highlight the differences among the habitats for sustenance of Aedes mosquitoes. RESULTS: Survey of larval habitats from the study area revealed significant differences (P<0.05) in the pupal productivity of Aedes among the habitats and months. Despite sewage drains being comparatively less utilized for breeding, the pupae were of higher biomass with corresponding adults having longer wings in contrast to other habitats. The nutrient reserve of the adults emerging from pupae of sewage drains was significantly higher (P<0.05), compared to other habitats, as reflected through the discriminant function analysis. INTERPRETATION & CONCLUSIONS: The present results showed that for both Ae. aegypti and Ae. albopictus, sewage drains were equally congenial habitat as were plastic, porcelain and earthen habitats. Availability of Aedes immature in sewage drains poses increased risk of dengue, and thus vector control programme should consider inclusion of sewage drains as breeding habitat of dengue vector mosquitoes. PMID- 26905249 TI - Insecticidal effect of plant extracts on Phlebotomus argentipes (Diptera: Psychodidae) in Bihar, India. AB - BACKGROUND & OBJECTIVES: Phlebotomus argentipes (Diptera: Psychodidae), the established vector for kala-azar is presently being controlled by indoor residual spray of DDT in kala-azar endemic areas in India. Search for non-hazardous and non-toxic biodegradable active molecules from botanicals may provide cost effective and eco-friendly alternatives to synthetic insecticides. The present study was aimed at evaluating various plant extracts from endemic and non-endemic areas of Bihar for their insecticidal activity against sandfly to identify the most effective plant extract. METHODS: Bio-assay test was conducted with larvae and adult of P. argentipes with different plant extracts collected in distilled water, hexane, ethyl acetate, acetone and methanol. Thin layer chromatography (TLC), column chromatography and high performance liquid chromatography (HPLC) were conducted for detection of active molecules. RESULTS: Adults and larvae of sandflies exposed to the aqueous extract of Nicotiana tabacum resulted in 100 per cent mortality. The hexane extract of Clerodendrum infortunatum was found to kill 77 per cent adults but was ineffective against larvae. Bio-assay test of the ninth fraction (hexane extract-methanol phase) separated by column chromatography was found to be 63 per cent effective. The purple spot on the TLC of this fraction indicated the presence of a diterpenoid. HPLC of this fraction detected nine compounds with two peaks covering 20.44 and 56.52 per cent areas with retention time of 2.439 and 5.182 min, respectively supporting the TLC results. INTERPRETATION & CONCLUSIONS: The column separated 9 [th] fraction of C. infortunatum extract was found to be effective in killing 63 per cent of adult P. argentipes. Compounds of this fraction need to be evaluated further for identification and characterization of the active molecule by conducting individual bio-assay tests followed by further fractionation and HPLC. Once the structure of the active molecule is identified and validated, it may be synthesized and formulated as a product. PMID- 26905251 TI - Neural Fibrolipoma of the Ankle: A Case Report and Review of the Literature. AB - Neural fibrolipomas are exceedingly rare benign tumors composed of hypertrophied fibrofatty tissue intermixed with nerve tissues. Our review of the published data identified only 15 cases of this tumor involving the foot and/or ankle region. An otherwise healthy 35-year-old male was referred for evaluation of a painless soft tissue mass present in the anterior left ankle. The mass had been present for approximately 6 to 7 years and had recently increased in size. Physical examination demonstrated a prominent, fluctuant mass present in the left ankle measuring 4 cm in diameter. The mass was not well-defined, was immobile, and did not transilluminate. No gross pedal deformity was present. Radiographic imaging revealed increased soft tissue prominence and density to the anterior ankle without bone involvement. Magnetic resonance imaging demonstrated a mass isointense to fat on all sequences without contrast enhancement, suggestive of a lipoma. Surgical excision was performed; the mass was yellow and lipomatous in nature. The mass was intimately associated with the superficial peroneal nerve, which had to be sacrificed during excision. The pathologic examination of the mass revealed findings consistent with a neural fibrolipoma. The patient healed uneventfully without recurrence. His only complaint was of some residual numbness in the medial foot. PMID- 26905250 TI - Cucurbitacin B inhibits the stemness and metastatic abilities of NSCLC via downregulation of canonical Wnt/beta-catenin signaling axis. AB - Lack of effective anti-metastatic drugs creates a major hurdle for metastatic lung cancer therapy. For successful lung cancer treatment, there is a strong need of newer therapeutics with metastasis-inhibitory potential. In the present study, we determined the anti-metastatic and anti-angiogenic potential of a natural plant triterpenoid, Cucurbitacin B (CuB) against non-small cell lung cancer (NSCLC) both in vitro and in vivo. CuB demonstrated a strong anti-migratory and anti-invasive ability against metastatic NSCLC at nanomolar concentrations. CuB also showed significant tumor angiogenesis-inhibitory effects as evidenced by the inhibition of migratory, invasive and tube-forming capacities of human umbilical vein endothelial cells. CuB-mediated inhibition of angiogenesis was validated by the inhibition of pre-existing vasculature in chick embryo chorio-allantoic membrane and matrigel plugs. Similarly, CuB inhibited the migratory behavior of TGF-beta1-induced experimental EMT model. The CuB-mediated inhibition of metastasis and angiogenesis was attributable to the downregulation of Wnt/beta catenin signaling axis, validated by siRNA-knockdown of Wnt3 and Wnt3a. The CuB mediated downregulation of Wnt/beta-catenin signaling was also validated using 4 (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis model in vivo. Collectively, our findings suggest that CuB inhibited the metastatic abilities of NSCLC through the inhibition of Wnt/beta-catenin signaling axis. PMID- 26905252 TI - Square, Random Fasciocutaneous Plantar Flaps for Treating Noninfected Diabetic Plantar Ulcers: A Patient Series. AB - In patients with diabetes, the off-loading cast has not been widely used to treat plantar ulcers because of its poor acceptance by patients and the high risk of side effects. We evaluated the safety and efficacy of an alternative surgical treatment: a square, fasciocutaneous random plantar flap to cover plantar ulcers. From December 2012 to February 2013, we enrolled 23 consecutive diabetic patients with deep neuropathic or neuroischemic plantar ulcers. Of these 23 patients, 9 underwent percutaneous transluminal angioplasty, 10 had the metatarsal removed, 3 underwent dorsiflexory, distal metatarsal osteotomies, 2 underwent first metatarsophalangeal joint resection and ray stabilization with Kirschner wires, and 1 each underwent midfoot exostectomy, sesamoidectomy, and partial calcanectomy. A square random fasciocutaneous plantar flap was created for all 23 patients. Two patients were excluded from the analysis for weightbearing on the involved foot within 24 hours of surgery. The healing rate was 100% for the remaining 21 patients, with healing by first intention in 15 (mean +/- standard deviation time to healing 30 +/- 13 days), by second intention in 5 (86 +/- 40 days), and by surgical revision in 1. The overall mean healing time was 44 +/- 31 days. During a mean follow-up of 724 +/- 275 days, no ulcer recurred; however, 1 transfer ulcer appeared on an adjacent metatarsal head. The use of a square random fasciocutaneous plantar flap is a safe and effective surgical option for treating neuropathic plantar ulcers, offering a high healing rate, a short healing time, and a low rate of recurrence. PMID- 26905253 TI - Posteromedial Ankle Impingement Caused by Hypertrophy of Talocalcaneal Coalition: A Report of Five Cases and Introduction of a Novel Index System. AB - Ankle impingement syndromes are common disorders that can be attributed to many factors. To the best of our knowledge, posteromedial ankle impingement syndromes caused by talocalcaneal coalition have never been previously reported. The present report describes 5 patients with posteromedial ankle pain and inversion limitation. The physical examination, radiographic, and magnetic resonance imaging findings suggested posteromedial ankle impingement syndrome and talocalcaneal coalition. The 5 patients underwent surgery after conservative treatment had failed. A novel index system, namely the angle and thickness of the medial talocalcaneal facet, was introduced. The talocalcaneal coalitions protruded medially and impinged on the malleolus medialis. The medial facet of the talus and calcaneum had a wider angle and thickness than normal. Pain relief was noted, and good long-term outcomes were achieved after resection of the medial prominence and coalition in all 5 patients. Talocalcaneal coalition can cause posteromedial ankle impingement syndrome when the coalition is hypertrophic. The angle and thickness of the medial talus facet could be a simple index to diagnose this disorder. PMID- 26905254 TI - Immediate Weightbearing of First Metatarsophalangeal Joint Fusion Comparing Buried Crossed Kirschner Wires Versus Crossing Screws: Does Incorporating the Sesamoids Into the Fusion Contribute to Higher Incidence of Bony Union? AB - First metatarsophalangeal joint (MTPJ) arthrodesis remains a commonly used and reliable procedure for a variety of pathologies of the first MTPJ. Many costly fixation constructions have been described to achieve union with first MTPJ arthrodesis. We hypothesized that the incidence of union would be the same for both buried Kirchner (K)-wire and solid crossed screw fixation with immediate weightbearing. To test this hypothesis, we retrospectively reviewed first MTPJ fusions performed by the senior author (C.A.C.) during a 6-year period and compared the incidence of union. Only patients who were immediately weightbearing in a surgical shoe and had undergone first MTPJ arthrodesis using K-wires or crossed screws were included. All patients had undergone incorporation of their sesamoids into the fusion. A total of 97 feet in 89 patients met the inclusion criteria. Of the 97 first MTPJ fusions, 48 (49.5%) had buried K-wire fixation and 49 (50.5%) crossed screw fixation. The mean age was 62 (range 41 to 75) years in the K-wire group and 60 (range 22 to 73) years in the crossed screw group. The mean follow-up period was 12.4 months in the K-wire group and 12.9 months in the crossed screw group. The rate of union in the K-wire group was 98% (1 nonunion) and the rate of union in the crossed screw group was 96% (2 nonunions). The 2 groups demonstrated similar high rates of fusion with immediate weightbearing, suggesting that less costly fixation is acceptable and effective for uncomplicated first MTPJ fusion. PMID- 26905255 TI - Proximal Opening Wedge Osteotomy Provides Satisfactory Midterm Results With a Low Complication Rate. AB - Hallux valgus is one of the most common foot deformities. Proximal opening wedge osteotomy is used for the treatment of moderate and severe hallux valgus with metatarsus primus varus. However, hypermobility of the first tarsometatarsal joint can compromise the results of the operation, and a paucity of midterm results are available regarding proximal open wedge osteotomy surgery. The aim of the present study was to assess the midterm results of proximal open wedge osteotomy in a consecutive series of patients with severe hallux valgus. Thirty one consecutive adult patients (35 feet) with severe hallux valgus underwent proximal open wedge osteotomy. Twenty patients (35.5%) and 23 feet (34.3%) were available for the final follow-up examination. The mean follow-up duration was 5.8 (range 4.6 to 7.0) years. The radiologic measurements and American Orthopaedic Foot and Ankle Society hallux-metatarsophalangeal-interphalangeal scores were recorded pre- and postoperatively, and subjective questionnaires were completed and foot scan analyses performed at the end of the follow-up period. The mean hallux valgus angle decreased from 38 degrees to 23 degrees , and the mean intermetatarsal angle correction decreased from 17 degrees to 10 degrees . The mean improvement in the American Orthopaedic Foot and Ankle Society hallux metatarsophalangeal-interphalangeal score increased from 52 to 84. Two feet (5.7%) required repeat surgery because of recurrent hallux valgus. No nonunions were identified. Proximal open wedge osteotomy provided satisfactory midterm results in the treatment of severe hallux valgus, with a low complication rate. The potential instability of the first tarsometatarsal joint does not seem to jeopardize the midterm results of the operation. PMID- 26905256 TI - Skin diseases among elderly patients attending skin clinic at the Regional Dermatology Training Centre, Northern Tanzania: a cross-sectional study. AB - BACKGROUND: As global population of the elderly continues to rise, a critical need to provide it with health services, including dermatology, will be significant, especially in developing countries like Tanzania. To adequately meet their dermatologic needs, knowledge of local patterns of skin conditions is vital. This study was aimed to describe the spectrum of skin diseases among elderly patients attending skin clinic at the Regional Dermatology Training Centre (RDTC) in Northern Tanzania. METHODS: A descriptive hospital based cross sectional study was conducted between January 2013 and April 2013 at RDTC and included all patients aged 55 years and above who consented to be examined. Diagnoses were clinical, diagnostic tests being done only when necessary. Ethical clearance to conduct the study was granted. RESULTS: A total of 142 patients, age ranges 55-99 years, median age of 67.5 years were seen. Eczemas were the leading disease group (43.7%), with unclassified eczemas (33.9%) predominating. Papulosquamous disorders (15.4%) were second with psoriasis (50%) being the leading disease. Infections (11.3% with fungal infections the leading group representing 5.6% of all diseases), tumours (9.8%: Kaposi's sarcoma 4.2%), vascular disorders 9.1% (lymphedema 4.9%), autoimmune disorders 7.7% (connective tissue diseases 4.9%), vitiligo 4.2%, nutritional diseases 2.1% (pellagra 0.7%), urticaria 0.7% and drug reactions 0.7%. CONCLUSIONS: Eczemas are the most common group of disorders among elderly patients presenting at RDTC. PMID- 26905258 TI - Electrooxidation of New Synthetic Cannabinoids: Voltammetric Determination of Drugs in Seized Street Samples and Artificial Saliva. AB - The electrochemical sensing of new psychoactive substances, synthetic cannabinoids (SCs), commonly marketed under the trade name "Spice" is explored for the first time. The electrooxidative transformations of 11 new indole and indazole SCs which are currently the predominant illicit smoking mixtures on the drug market is performed using cyclic and differential pulse voltammetry with various commercially available electrodes (Pt, GC, Bdd). It is found that SCs exhibit voltammetric responses that can be used for their detection in smoking mixtures and artificial saliva with limits of detection in the nanomolar range. The indole-based SCs exhibited an anodic peak at ~1.5 V (vs Ag/Ag(+)) and ~1.2 V (vs Ag/AgCl) in acetonitrile and artificial saliva, respectively, and the indazoles exhibited corresponding peaks at ~1.7 V and ~1.5 V. The voltammetric procedure was evaluated by prescreening of SCs in 12 confiscated street samples that were also independently analyzed by GC-MS and LC-MS techniques. A good agreement between the three analytical protocols was found. Voltammetry provides a tool for the prescreening of synthetic cannabinoid derivatives in seized materials and biological samples. PMID- 26905259 TI - What does it take to provide cancer patients with comprehensive medication therapy management services for oral chemotherapy? PMID- 26905257 TI - Effects of cytosine modifications on DNA flexibility and nucleosome mechanical stability. AB - Cytosine can undergo modifications, forming 5-methylcytosine (5-mC) and its oxidized products 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-fC) and 5 carboxylcytosine (5-caC). Despite their importance as epigenetic markers and as central players in cellular processes, it is not well understood how these modifications influence physical properties of DNA and chromatin. Here we report a comprehensive survey of the effect of cytosine modifications on DNA flexibility. We find that even a single copy of 5-fC increases DNA flexibility markedly. 5-mC reduces and 5-hmC enhances flexibility, and 5-caC does not have a measurable effect. Molecular dynamics simulations show that these modifications promote or dampen structural fluctuations, likely through competing effects of base polarity and steric hindrance, without changing the average structure. The increase in DNA flexibility increases the mechanical stability of the nucleosome and vice versa, suggesting a gene regulation mechanism where cytosine modifications change the accessibility of nucleosomal DNA through their effects on DNA flexibility. PMID- 26905260 TI - Photoinduced Charge Separation in Porphyrin Ion Pairs. AB - Ion pairs between porphyrin-type compounds have been successfully employed for spectral sensitization of semiconductor surfaces and for the preparation of collective binary ionic materials for photonic and (photo)catalytic applications. The understanding of the photophysical processes occurring within ion-paired porphyrin dimers is thus of remarkable importance for the optimization and improvement of such systems. Herein the ion-pair species formed between ZnTMePyP(4+) (Zn1) or H2TMePyP(4+) (H21) and ZnTPPS(4-) (Zn2) or H2TPPS(4-) (H22) in a variety of solvent mixtures are characterized and their photophysics thoroughly investigated by time-resolved techniques. In all the systems studied, very fast and efficient photoinduced charge separation is observed, with the cationic porphyrin being reduced and the anionic one oxidized. Interestingly, despite the very short charge separation distance, the lifetime for charge recombination, depending on the energy gap, can extend into the nanosecond time domain, showing great potential for the utilization of this molecular design within energy conversion schemes. PMID- 26905261 TI - Identification and characterization of kiss2 and kissr2 homologs in Paralichthys olivaceus. AB - The role of kisspeptin in puberty onset has been extensively investigated by neuroendocrinologists in the past decade. In the present study, we first cloned and analyzed Pokiss2 and Pokissr2 genes in Paralichthys olivaceus, a Pleuronectiformes fish. By 5'/3' rapid amplification of cDNA ends (RACE), the P. olivaceus kiss2 gene (Pokiss2) and two isoforms of the P. olivaceus kissr2 gene (Pokissr2) transcripts were cloned. During development, Pokissr2 was maternally inherited but Pokiss2 was not, and their expression reached maximum and minimum levels, respectively, when the gonads began to develop. Analysis of tissue distribution revealed that Pokiss2 and Pokissr2 transcripts were predominantly expressed in the brain and gonads, with expression levels in females higher than those in males. Moreover, Pokiss2 and Pokissr2 both showed significantly higher expression in brains and gonads during puberty. In situ hybridization of the ovary at pre-vitellogenesis stage and testis at spermatogonial proliferation stage revealed that both Pokiss2 and Pokissr2 were expressed in spermatocyte, oocytes, and some somatic cells. Our results also showed significantly stronger Pokiss2 expression in the area of the third ventricle of females than males and no Pokissr2 expression in this region in both sexes. These results lay a strong foundation for understanding the role of kisspeptin in neuroendocrine system in teleosts, in particular in Pleuronectiformes. PMID- 26905262 TI - Characterization of FGFR1 Locus in sqNSCLC Reveals a Broad and Heterogeneous Amplicon. AB - FGFR1 amplification occurs in ~20% of sqNSCLC and trials with FGFR inhibitors have selected FGFR1 amplified patients by FISH. Lung cancer cell lines were profiled for sensitivity to AZD4547, a potent, selective inhibitor of FGFRs 1-3. Sensitivity to FGFR inhibition was associated with but not wholly predicted by increased FGFR1 gene copy number. Additional biomarker assays evaluating expression of FGFRs and correlation between amplification and expression in clinical tissues are therefore warranted. We validated nanoString for mRNA expression analysis of 194 genes, including FGFRs, from clinical tumour tissue. In a panel of sqNSCLC tumours 14.4% (13/90) were FGFR1 amplified by FISH. Although mean FGFR1 expression was significantly higher in amplified samples, there was significant overlap in the range of expression levels between the amplified and non-amplified cohorts with several non-amplified samples expressing FGFR1 to levels equivalent to amplified samples. Statistical analysis revealed increased expression of FGFR1 neighboring genes on the 8p12 amplicon (BAG4, LSM1 and WHSC1L1) in FGFR1 amplified tumours, suggesting a broad rather than focal amplicon and raises the potential for codependencies. High resolution aCGH analysis of pre-clinical and clinical samples supported the presence of a broad and heterogeneous amplicon around the FGFR1 locus. In conclusion, the range of FGFR1 expression levels in both FGFR1 amplified and non-amplified NSCLC tissues, together with the breadth and intra-patient heterogeneity of the 8p amplicon highlights the need for gene expression analysis of clinical samples to inform the understanding of determinants of response to FGFR inhibitors. In this respect the nanoString platform provides an attractive option for RNA analysis of FFPE clinical samples. PMID- 26905264 TI - Introduction to Frontiers in Macromolecular and Supramolecular Science: Part 2. PMID- 26905265 TI - Review of the Clinical and Economic Burden of Antibody-Mediated Rejection in Renal Transplant Recipients. AB - Antibody-mediated rejection (AbMR) is a leading cause of late graft loss in kidney transplant recipients, accounting for up to 60% of late graft failures. AbMR manifests as two distinct phenotypes: the first occurs in the immediate post transplant period in sensitized patients; the second occurs in the late post transplant period and has been associated with non-adherence to immunosuppression. The present review summarizes the current treatment options for AbMR, its clinical and economic burden, and approaches for reducing the risk of AbMR. While AbMR is typically refractory to treatment with corticosteroids, there are numerous other approaches focused on removal, inhibition or neutralization of donor-specific antibodies, or inhibition of complement-mediated allograft damage. AbMR treatment is generally expensive with one US study reporting costs of USD 49,000-155,000 per episode. However, leaving AbMR untreated puts patients at high risk of capillaritis, microangiopathy, necrosis and graft failure, which may ultimately result in much greater costs associated with a return to dialysis. Given the barriers to treatment, which include the high cost and the fact that pharmacologic treatments are currently used off label, prevention of AbMR is important, with improvement in patient adherence to immunosuppression a key strategic approach that may be worthy of further evaluation. FUNDING: Astellas Pharma EMEA Limited. PMID- 26905263 TI - Drug activity screening based on microsomes-hydrogel system in predicting metabolism induced antitumor effect of oroxylin A. AB - A novel microsomes-hydrogel added cell culture system (MHCCS) was employed in the antitumor activity screening of natural compounds, aiming to achieve drug screening with better in vivo correlation, higher initiative to explore the potential active metabolites, and investigation of the antitumor mechanism from the perspective of metabolism. MTT assay and cell apoptosis detection showed that test drug oroxylin A (OA) had enhanced cytotoxicity and wogonin (W) with reduced cytotoxicity on MCF-7 cell line upon MHCCS incubation. In vivo antitumor evaluations also demonstrated that OA induced higher tumor inhibition than W at the same dosage. To explore the reasons, nine major metabolites of OA were separated and collected through UPLC-Q-TOF and semi-preparative HPLC. Metabolites M318 exhibited higher cytotoxicity than OA and other metabolites by MTT assay. (1)H NMR spectrums, HPLC and TOF MS/MS results revealed that OA was catalyzed into its active metabolite M318 via a ring-opening reaction. M318 induced significant cell apoptosis and S-phase arrest through affecting tumor survival related genes after mechanism study. In conclusion, our MHCCS could be a useful tool for drug activity screening from a perspective of metabolism. PMID- 26905266 TI - Mesalazine Modified-Release Tablet in the Treatment of Ulcerative Colitis in the Remission Phase: A Chinese, Multicenter, Single-Blind, Randomized Controlled Study. AB - INTRODUCTION: This study aimed to compare the efficacy and safety of two mesalazine formulations in the treatment of Chinese patients with ulcerative colitis (UC) in the remission phase. METHODS: In this multicenter, single-blind, randomized controlled study conducted from November 2010 to August 2012, 251 patients with UC from 18 hospitals were enrolled. The patients were randomized to treatment with mesalazine modified-release tablets (MR group, n = 126) or other enteric-coated tablets (EC group, n = 125), at 800 mg three-times daily for 48 weeks. The primary efficacy parameter was the rate of non-emergence of bloody stool. If the lower limit of the 95% confidence interval (CI) of the primary efficacy measure was over -10%, the modified-release tablets were considered non inferior to the enteric-coated tablets. The secondary efficacy parameters included the period of non-emergence of bloody stool and the period of non recurrence of UC. The incidences of adverse events and adverse drug reactions were compared between the two groups. RESULTS: At 48 weeks of maintenance treatment, the rates of non-emergence of bloody stool were 82.99% (95% CI 73.53 92.45%) and 73.30% (95% CI 64.04-82.56%) in the MR and EC groups, respectively, and the difference between the two groups was 9.69% (95% CI -1.15-20.53%). There was no significant difference in the period of non-emergence of bloody stool and the period of non-recurrence of UC between the two groups (P > 0.05). The incidences of adverse events were 48.78% (60/123) and 48.00% (60/125) in the MR and EC groups, respectively (P = 0.902). The incidences of adverse drug reactions were 16.26% (20/123) and 13.60% (17/125) in the MR and EC groups, respectively (P = 0.556). CONCLUSION: Mesalazine modified-release tablets were non-inferior to the enteric-coated tablets and may be considered an effective and safe treatment alternative for the maintenance of remission in Chinese patients with UC. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01257399. FUNDING: Tillotts Pharma AG. PMID- 26905267 TI - Effects of coffee consumption on serum uric acid: systematic review and meta analysis. AB - OBJECTIVE: Study results on the effects of coffee consumption on serum uric acid (UA) have been conflicting. The aim of this study is to analyze the literature regarding the effect of coffee consumption on serum UA. METHODS: We searched MEDLINE, EMBASE, the Cochrane library, and KoreaMed for all articles published before January 2015. Studies with quantitative data on coffee consumption and serum UA level were included. Coffee consumption and serum UA level were identified with/without the risk of gout. RESULTS: Nine studies published between 1999 and 2014 were included, containing a total of 175,310 subjects. Meta analysis demonstrated that coffee has a significantly lowering effect on serum UA, where there are gender differences in the amount of coffee required to lower serum UA. Women (4-6 cups/day) need more coffee to lower serum UA than men (1-3 cups/day). Meta-analysis showed that coffee intake of 1 cup/day or more was significantly associated with reduction of the risk of gout, with a negative correlation with the amount of daily coffee intake for both genders. CONCLUSIONS: This is the first systematic review on the effects of coffee consumption on serum UA. Based on our study, moderate coffee intake might be advocated for primary prevention of hyperuricemia and gout in both genders. PMID- 26905268 TI - Simultaneous Detection and Quantification of Phytohormones by a Sensitive Method of Separation in Culture of Pseudomonas sp. AB - A high-performance thin-layer chromatography (HPTLC)-based sensitive, rapid and stringent protocol is designed for detection and quantification of five phytohormones simultaneously. Culture filtrate of Pseudomonas bacteria was acidified with 7 M HCl and extracted with an equal volume of ethyl acetate to separate abscisic acid (ABA), jasmonic acid (JA), gibberellic acid (GA3), and indole-3-acetic acid (IAA). Kinetin was extracted from the remaining water fraction of the same extract. Various extracts were loaded on silica gel 60 F254 foil using Linomat 5 spray on applicator. Standard phytohormones were also loaded adjacent to the sample, and the foils were developed with isopropanol-ammonia water [10:1:1 (v/v)] as the mobile phase. A quantitative estimation of the separated ABA, kinetin, JA, GA3, and IAA was performed by measuring the absorbance at 260, 275, 295, 265, and 280 nm, respectively. HPTLC method was found to be cost effective, robust technique that can be routinely used for simultaneous phytohormone detection in plant or bacterial samples. The present work is not only useful for detection and quantification of phytohormones but also for screening of phytohormone producing microorganisms. PMID- 26905269 TI - A mechanistic study of in situ chemical cleaning-in-place for a PTFE flat sheet membrane: fouling mitigation and membrane characterization. AB - This study aimed at unfolding the role and mechanisms of chemically enhanced cleaning-in-place (CIP) regimes in fouling control of polytetrafluoroethylene (PTFE) made flat sheet (FS) membrane bio-reactors (MBRs). The trans-membrane pressure (TMP) was successfully maintained below 10 kPa using a daily CIP regime consisting of 100 to 600 mg l(-1) of NaOCl and cake layer resistance control was shown to be critical for effective high-flux MBR operation. In contrast, in the control unit without the CIP, the TMP exceeded 35 kPa at a flux of 40 LMH. The extracellular polymeric substances associated with proteins (EPSprotein) were also controlled effectively with a daily application of the CIP to the fouled membrane. Moreover, the CIP prompted a thinner and looser bio-cake layer on the membrane surface, suggesting that in situ CIP can be a favorable method to control FS membrane fouling at high-flux MBR operation. PMID- 26905270 TI - Associations of total and free 25OHD and 1,25(OH)2D with serum markers of inflammation in older men. AB - Vitamin D is hypothesized to suppress inflammation. We tested total and free vitamin D metabolites and their association with inflammatory markers. Interleukin-6 levels were lower with higher 25-hydroxyvitamin D. 1,25 dihydroxyvitamin D and free 25OHD associations mirrored those of 25OHD. However, associations for the two metabolites diverged for tumor necrosis factor alpha (TNF-alpha) soluble receptors. INTRODUCTION: Vitamin D is hypothesized to suppress inflammation, and circulating 25-hydroxyvitamin D (25OHD) and inflammatory markers are inversely correlated. However, total serum 25OHD may not be the best indicator of biologically active vitamin D. METHODS: We tested serum total 25OHD, total 1,25(OH)2D, vitamin D binding protein (DBP), and estimated free 25OHD and free 1,25(OH)2D associations with inflammatory markers serum interleukin-6 (IL-6), TNF-alpha and their soluble receptors, interleukin-10 (IL 10), and C-reactive protein (CRP) as continuous outcomes and the presence of >=2 inflammatory markers in the highest quartile as a dichotomous outcome, in a random subcohort of 679 men in the Osteoporotic Fractures in Men (MrOS) study. RESULTS: IL-6 was lower in men with higher 25OHD (-0.23 MUg/mL per standard deviation (SD) increase in 25OHD, 95 % confidence intervals (CI) -0.07 to -0.38 MUg/mL) and with higher 1,25(OH)2D (-0.20 MUg/mL, 95 % CI -0.0004 to -0.39 MUg/mL); free D associations were slightly stronger. 25OHD and DBP, but not 1,25(OH)2D, were independently associated with IL-6. TNF-alpha soluble receptors were inversely associated with 1,25(OH)2D but positively associated with 25OHD, and each had independent effects. The strongest association with >=2 inflammatory markers in the highest quartile was for free 1,25(OH)2D (odds ratios (OR) 0.70, 95 % CI 0.54 to 0.89 per SD increase in free 1,25(OH)2D). CONCLUSIONS: Associations of 1,25(OH)2D and free 25OHD with IL-6 mirrored those of 25OHD, suggesting that 1,25(OH)2D and free D do not improve upon 25OHD in population based IL-6 studies. However, associations for the two metabolites diverged for TNF-alpha soluble receptor, warranting examination of both metabolites in studies of TNF-alpha and its antagonists. PMID- 26905271 TI - Quality of life, resource use, and costs related to hip fracture in Estonia. AB - We assessed the impact of hip fracture on health-related quality of life (HRQoL) and costs in Estonia. The mean 18-month HRQoL loss in quality adjusted life years (QALY) was estimated at 0.31, and the average cumulative cost from a societal perspective was 8146 euros per hip fracture patient. INTRODUCTION: The aim of this study is to estimate the impact of hip fracture on HRQoL, resource consumption, and cost over 18 months after the fracture among individuals aged over 50 in Estonia. METHODS: A cohort of 205 hip fracture patients >=50 years was followed up for 18 months. HRQoL was estimated before fracture (recall), after fracture, and at 4, 12, and 18 months using the EQ-5D instrument. Health care utilization and costs were obtained from a public health insurance fund database; social, informal, and indirect costs were estimated using patient-reported data. RESULTS: Hip fracture resulted in the mean 18-month HRQoL loss of 0.31 QALYs. The mean 18-months cumulative cost of hip fracture from a societal perspective was estimated at 8146 (95 % CI 6236-10717) euros per patient. Most of the cost was related to health care (56 %) and informal care (33 %), while social care contributed only 5 %. Utilization of outpatient rehabilitation and nursing care was low (8 % of patients). CONCLUSIONS: The impact of hip fracture on HRQoL and cost was substantial. Despite appropriate inpatient care, utilization of rehabilitation, nursing care, and social care were low and potentially insufficient to meet the needs of patients with low HRQoL. The shortfall may partially explain a remarkably high use of informal care. PMID- 26905272 TI - Repetitive Transcranial Magnetic Stimulation/Behavioral Intervention Clinical Trial: Long-Term Follow-Up of Outcomes in Congenital Hemiparesis. AB - OBJECTIVE: The purpose of this study was to examine long-term outcomes of nonpharmacological intervention in children and adolescents with stroke utilizing repetitive transcranial magnetic stimulation (rTMS) to the primary motor cortex combined with constraint- induced movement therapy (CIMT) to improve motor function in the paretic hand. Outcome measures included function, satisfaction, and medical status review. METHODS: Fourteen of the original 19 participants (74%) from our rTMS/CIMT clinical trial (real rTMS+CIMT, n = 8; and sham rTMS+CIMT, n = 6) were evaluated. The median age of the subjects at follow up was 13.4 years (range 11-20 years old, 50% male). Median time to follow-up was 47.5 months (range 21-57 months). Descriptive statistics were conducted using frequencies and counts. Motor performance was measured using the Assisting Hand Assessment (AHA) and Canadian Occupational Performance Measure (COPM). Satisfaction was reported with use of the COPM and TMS Tolerance Survey. Open ended interview was conducted for feedback on study experience and subjective perspectives of current functional status. RESULTS: Overall, seven of eight individuals who received real rTMS and five of six individuals who received sham rTMS maintained or improved AHA scores. Six of 14 participants reported new onset of co-occurring conditions (four individuals in the real rTMS group, two individuals in the sham rTMS group). The majority (86%) of participants reported study satisfaction. Review of medical status revealed co-occurring conditions including: Epilepsy, obsessive-compulsive disorder, anxiety, depression, unspecified mood disorder, and undiagnosed inattentiveness. CONCLUSIONS: Long term outcomes of rTMS/CIMT in pediatric stroke were investigated. Variability in performance and unattributed symptoms were noted. Considering the prevalence of co-occurring conditions in children and adolescents with stroke, new-onset symptoms were not attributed to original intervention. With the small sample size, the impact of rTMS on long-term outcomes cannot be fully determined from these data. Characterizing long-term outcomes through performance, participant perspectives, and medical status allows comprehensive assessment of rTMS/CIMT intervention efficacy. PMID- 26905273 TI - Age-Related Changes in Processing Simultaneous Amplitude Modulated Sounds Assessed Using Envelope Following Responses. AB - Listening conditions in the real world involve segregating the stimuli of interest from competing auditory stimuli that differ in their sound level and spectral content. It is in these conditions of complex spectro-temporal processing that listeners with age-related hearing loss experience the most difficulties. Envelope following responses (EFRs) provide objective neurophysiological measures of auditory processing. EFRs were obtained to two simultaneous sinusoidally amplitude modulated (sAM) tones from young and aged Fischer-344 rats. One was held at a fixed suprathreshold sound level (sAM1FL) while the second varied in sound level (sAM2VL) and carrier frequency. EFR amplitudes to sAM1FL in the young decreased with signal-to-noise ratio (SNR), and this reduction was more pronounced when the sAM2VL carrier frequency was spectrally separated from sAM1FL. Aged animals showed similar trends, while having decreased overall response amplitudes compared to the young. These results were replicated using an established computational model of the auditory nerve. The trends observed in the EFRs were shown to be due to the contributions of the low-frequency tails of high-frequency neurons, rather than neurons tuned to the sAM1FL carrier frequency. Modeling changes in threshold and neural loss reproduced some of the changes seen with age, but accuracy improved when combined with an additional decrease representing synaptic loss of auditory nerve neurons. Sound segregation in this case derives primarily from peripheral processing, regardless of age. Contributions by more central neural mechanisms are likely to occur only at low SNRs. PMID- 26905274 TI - Advances in the Management of Anal Cancer. AB - Although anal squamous cell carcinoma (ASCC) is an uncommon malignancy, its incidence has been increasing markedly in recent decades due to its association with human papilloma virus (HPV) infection. The well-established standard of care for localized ASCC consists of the combination of 5-fluorouracil (5FU) and mitomycin (MMC) chemotherapy, concurrent with external beam radiation therapy (EBRT). However, newer techniques are being actively pursued, including the use of newer radiation therapy (RT) technologies, such as intensity-modulated radiation therapy (IMRT). The areas of debate and development include the dosing and timing of MMC delivery, the role of cisplatin chemotherapy as an alternative to MMC, the replacement of the standard 96-h infusion of 5FU with oral capecitabine, the use of targeted chemotherapy agents, and the duration and dose of RT. PMID- 26905275 TI - Effects of an inducible aiiA gene on disease resistance in Eucalyptus urophylla * Eucalyptus grandis. AB - N-acyl-homoserine lactones (AHLs) are metabolites of mostly gram-negative bacteria and are critical signaling molecules in bacterial quorum-sensing systems. At threshold concentrations, AHLs can activate the expression of pathogenic genes and induce diseases. Therefore, reducing AHL concentrations is a key point of disease control in plants. AHL-lactonase, which is expressed by aiiA, is widespread in Bacillus sp and can hydrolyze AHLs. In the present study, we cloned aiiA from Bacillus subtilis by PCR. A plant expression vector of aiiA was constructed and name Pcam-PPP3-aiiA, in which expression of aiiA was controlled by the pathogen-inducible plant promoter PPP3. The recombinant plasmid was transferred into Eucalyptus * urophylla * E. grandis by an Agrobacterium mediated transformation. PCR and Southern blotting showed that aiiA was successfully integrated into the E. urophylla * E. grandis genome and its expression was induced by Ralstonia solanacearum 12 h after inoculation, as shown by reverse transcription-PCR. The transcription efficacy of aiiA increased 43.88 , 30.65-, and 18.95-fold after inoculation with R. solanacearum, Erwinia carotovora ssp. zeae (Sabet) and Cylindrocladium quinqueseptatum, respectively as shown by RT-real-time PCR. Transgenic E.urophylla * E.grandis expressing the AIIA protein exhibited significantly enhanced disease resistance compared to non transgenic plants by delaying the onset of wilting and reducing the disease index. PMID- 26905276 TI - Diabetes, glucose tolerance, and the risk of sudden cardiac death. AB - BACKGROUND: Diabetes predisposes to sudden cardiac death (SCD). However, it is uncertain whether greater proportion of cardiac deaths are sudden among diabetes patients than other subjects. It is also unclear whether the risk of SCD is pronounced already early in the course of the disease. The relationship of impaired glucose tolerance (IGT) and SCD is scarcely documented. METHODS: A general population cohort of 10594 middle-aged subjects (mean age 44 years, 52.6 % male, follow-up duration 35-41 years) was divided into diabetes patients (n = 82), subjects with IGT (n = 3806, plasma glucose >=9.58 mmol/l in one-hour glucose tolerance test), and controls (n = 6706). RESULTS: Diabetes patients had an increased risk of SCD after adjustment confounders (hazard ratio 2.62, 95 % confidence interval 1.46-4.70, p = 0.001) but risk for non-sudden cardiac death was similarly increased and the proportion of SCD of cardiac deaths was not increased. The SCD risk persisted after exclusion of subjects with baseline cardiac disease or non-fatal cardiac events during the follow-up. Subjects with IGT were at increased risk for SCD (univariate hazard ratio 1.51; 95 % confidence interval 1.31-1.74; p < 0.001) and also for non-sudden cardiac deaths and non fatal cardiac events but adjustments for other risk factors attenuated these effects. CONCLUSIONS: Diabetes was associated with increased risk of SCD but also the risk of non-sudden cardiac death was similarly increased. The proportion of cardiac deaths being sudden in subjects with diabetes was not increased. The higher SCD risk in diabetes patients was independent of known cardiac disease at baseline or occurrence of non-fatal cardiac event during the follow-up. PMID- 26905277 TI - I Think, Therefore Eyeblink: The Importance of Contingency Awareness in Conditioning. AB - Can conditioning occur without conscious awareness of the contingency between the stimuli? We trained participants on two separate reaction time tasks that ensured attention to the experimental stimuli. The tasks were then interleaved to create a differential Pavlovian contingency between visual stimuli from one task and an airpuff stimulus from the other. Many participants were unaware of the contingency and failed to show differential eyeblink conditioning, despite attending to a salient stimulus that was contingently and contiguously related to the airpuff stimulus over many trials. Manipulation of awareness by verbal instruction dramatically increased awareness and differential eyeblink responding. These findings cast doubt on dual-system theories, which propose an automatic associative system independent of cognition, and provide strong evidence that cognitive processes associated with awareness play a causal role in learning. PMID- 26905278 TI - Mortality, Morbidity, and Developmental Outcomes in Infants Born to Women Who Received Either Mefloquine or Sulfadoxine-Pyrimethamine as Intermittent Preventive Treatment of Malaria in Pregnancy: A Cohort Study. AB - BACKGROUND: Little is known about the effects of intermittent preventive treatment of malaria in pregnancy (IPTp) on the health of sub-Saharan African infants. We have evaluated the safety of IPTp with mefloquine (MQ) compared to sulfadoxine-pyrimethamine (SP) for important infant health and developmental outcomes. METHODS AND FINDINGS: In the context of a multicenter randomized controlled trial evaluating the safety and efficacy of IPTp with MQ compared to SP in pregnancy carried out in four sub-Saharan countries (Mozambique, Benin, Gabon, and Tanzania), 4,247 newborns, 2,815 born to women who received MQ and 1,432 born to women who received SP for IPTp, were followed up until 12 mo of age. Anthropometric parameters and psychomotor development were assessed at 1, 9, and 12 mo of age, and the incidence of malaria, anemia, hospital admissions, outpatient visits, and mortality were determined until 12 mo of age. No significant differences were found in the proportion of infants with stunting, underweight, wasting, and severe acute malnutrition at 1, 9, and 12 mo of age between infants born to women who were on IPTp with MQ versus SP. Except for three items evaluated at 9 mo of age, no significant differences were observed in the psychomotor development milestones assessed. Incidence of malaria, anemia, hospital admissions, outpatient visits, and mortality were similar between the two groups. Information on the outcomes at 12 mo of age was unavailable in 26% of the infants, 761 (27%) from the MQ group and 377 (26%) from the SP group. Reasons for not completing the study were death (4% of total study population), study withdrawal (6%), migration (8%), and loss to follow-up (9%). CONCLUSIONS: No significant differences were found between IPTp with MQ and SP administered in pregnancy on infant mortality, morbidity, and nutritional outcomes. The poorer performance on certain psychomotor development milestones at 9 mo of age in children born to women in the MQ group compared to those in the SP group may deserve further studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT00811421. PMID- 26905284 TI - Prevalence of binge drinking and associated behaviours among 3286 college students in France. AB - BACKGROUND: Studies conducted on characteristics of binge drinking and associated behaviours in college student populations are scarce especially in France. Hence, it is important to identify risk factors for binge drinking at university, especially those which may be changed. The aim of this study was to assess the prevalence of binge drinking and associated behaviours across a large sample of college students in Upper Normandy (France). METHODS: A cross sectional study was performed between November 2009 and February 2013 and data on socioeconomic characteristics and behavioural risk factors were collected: alcohol (consumption and misuse of alcohol, occasional and frequent binge drinking), tobacco, cannabis, cyberaddiction, stress and depression. An anonymous self-administered questionnaire was filled out by college student volunteers from Upper Normandy (France) either online or by paper questionnaire. Analyses were performed using multivariate logistic regression models. RESULTS: A total of 3286 students were included. The mean (Standard Deviation (SD)) age of students was 20.8 years (SD = 2.1) with a male-female ratio of 0.60. The prevalence of binge drinking in the never, occasional and frequent categories was respectively 34.9%, 51.3%, and 13.8%. The mean number of units of alcohol consumed per week (except BD episodes) was 0.78 for never, 3.7 for occasional and 10.5 for frequent binge drinkers (p < 0.0001). A positive relation was observed between frequent binge drinking and the following: male gender (AOR 4.77 95% CI (3.43-6.63); p < 0.0001), living in rented accommodation AOR 1.70 95% CI (1.21-2.40; p < 0.0001), attending business school AOR 4.72 95% CI (2.76-8.08; p < 0.0001), regular practice of sport AOR 1.70 95% CI (1.24-2.34; p = 0.001), smoking AOR 5.89 95% CI (4.03-8.60; p < 0.0001), occasional cannabis use AOR 12.66 95% CI (8.97-17.87;p < 0.0001), and alcohol abuse AOR 19.25 95% CI (13.4-27.72; p < .0001). A negative association was observed between frequent binge drinking and grant holder status, living in couples, and stress. CONCLUSIONS: This study highlights the spread of binge drinking among college students and identifies student populations at risk: male gender, living in rented accommodation, regular practice of sport, and other risk behaviours such as use of tobacco, cannabis and alcohol. These behaviours increase with the frequency of binge drinking. PMID- 26905285 TI - Large Scale Triboelectric Nanogenerator and Self-Powered Pressure Sensor Array Using Low Cost Roll-to-Roll UV Embossing. AB - Triboelectric nanogenerators (TENGs) have emerged as a potential solution for mechanical energy harvesting over conventional mechanisms such as piezoelectric and electromagnetic, due to easy fabrication, high efficiency and wider choice of materials. Traditional fabrication techniques used to realize TENGs involve plasma etching, soft lithography and nanoparticle deposition for higher performance. But lack of truly scalable fabrication processes still remains a critical challenge and bottleneck in the path of bringing TENGs to commercial production. In this paper, we demonstrate fabrication of large scale triboelectric nanogenerator (LS-TENG) using roll-to-roll ultraviolet embossing to pattern polyethylene terephthalate sheets. These LS-TENGs can be used to harvest energy from human motion and vehicle motion from embedded devices in floors and roads, respectively. LS-TENG generated a power density of 62.5 mW m(-2). Using roll-to-roll processing technique, we also demonstrate a large scale triboelectric pressure sensor array with pressure detection sensitivity of 1.33 V kPa(-1). The large scale pressure sensor array has applications in self-powered motion tracking, posture monitoring and electronic skin applications. This work demonstrates scalable fabrication of TENGs and self-powered pressure sensor arrays, which will lead to extremely low cost and bring them closer to commercial production. PMID- 26905286 TI - A simplified measurement of pulse wave velocity is not inferior to standard measurement in young adults and children. AB - The standard measurement of pulse wave velocity (PWV) is restricted by the need for simultaneous tonometry measurements requiring two technicians and expensive equipment, limiting this technique to well-resourced settings. In this preliminary study, we compared a simplified method of pulse wave detection from the finger and toe to pulse wave detection from the carotid and radial arteries using applanation tonometry in children and young adults. We hypothesized that the simplified method of PWV measurement would strongly correlate with the standard measurement in different age groups and oxygen conditions. Participants included (a) boys and girls aged 8-12 years and (b) men and women aged 18-40 years. Participants rested supine while carotid and radial artery pulse waves were measured using applanation tonometry and finger and toe pulse waves were simultaneously collected using a Finometer Midi and a piezo-electric pulse transducer, respectively. These measurements were repeated under hypoxic conditions. Finger-toe PWV measurements were strongly correlated to carotid radial PWV in adults (R=0.58; P=0.011), but not in children (R=0.056; P=0.610). Finger-toe PWV was sensitive enough to show increases in PWV with age (P<0.0001) and hypoxia in children (P<0.0001) and adults (P=0.003). These results indicate that the simplified measurement of finger-toe PWV strongly correlates with the standard measurement of carotid-radial PWV in adults, but not in children. However, finger-toe PWV can be used in either population to determine changes with hypoxia. PMID- 26905288 TI - Proteins of the corneal stroma: importance in visual function. AB - The human cornea, consisting of five layers, is the transparent tissue that refracts and transmits light to the lens and retina, providing about two thirds of the refractive power of the eye. The stroma layer comprises nearly 90 % of the thickness of the cornea and thus plays a pivotal role in normal visual function. The bulk of this layer is constituted by proteins in the extracellular martrix secreted by the corneal epithelial, stroma, and endothelial cells. Clinical research has shown that corneal stroma diseases are common and involve conditions such as infections, injuries, and genetic defects, which cause severe visual disturbances or even blindness. To improve our understanding of the basic molecular mechanisms involved in the physiological and pathological activities of the corneal stroma, its proteins have been brought into the limelight to determine their crucial and irreplaceable roles. The data presented in a previous study have demonstrated the presence of 1679 proteins in the stroma, and this data set has subsequently been perfected by utilizing a highly sensitive isobaric peptide-labeling approach. According to their manifestations, these proteins can be classified as a gel-like organic material composed of proteoglycans, enzymes, and hemocyanin-binding proteins and a network of filaments composed of collagen, elastin, keratin, vimentin, and interconnected filaments comprising fibronectin and laminin. The aim of this review is to describe some corneal stroma proteins by highlighting their major functions and valuable applications in ophthalmologic research toward the better characterization and treatment of eye diseases. PMID- 26905287 TI - Impaired theta-gamma coupling in APP-deficient mice. AB - Amyloid precursor protein (APP) is critically involved in the pathophysiology of Alzheimer's disease, but its physiological functions remain elusive. Importantly, APP knockout (APP-KO) mice exhibit cognitive deficits, suggesting that APP plays a role at the neuronal network level. To investigate this possibility, we recorded local field potentials (LFPs) from the posterior parietal cortex, dorsal hippocampus and lateral prefrontal cortex of freely moving APP-KO mice. Spectral analyses showed that network oscillations within the theta- and gamma-frequency bands were not different between APP-KO and wild-type mice. Surprisingly, however, while gamma amplitude coupled to theta phase in all recorded regions of wild-type animals, in APP-KO mice theta-gamma coupling was strongly diminished in recordings from the parietal cortex and hippocampus, but not in LFPs recorded from the prefrontal cortex. Thus, lack of APP reduces oscillatory coupling in LFP recordings from specific brain regions, despite not affecting the amplitude of the oscillations. Together, our findings reveal reduced cross-frequency coupling as a functional marker of APP deficiency at the network level. PMID- 26905290 TI - 32. Deutscher Krebskongress Krebsmedizin heute: praventiv, personalisiert, prazise und partizipativ, Berlin, 24.-27. Februar 2016: Abstracts. PMID- 26905289 TI - Characterization and engineering of the biosynthesis gene cluster for antitumor macrolides PM100117 and PM100118 from a marine actinobacteria: generation of a novel improved derivative. AB - BACKGROUND: PM100117 and PM100118 are glycosylated polyketides with remarkable antitumor activity, which derive from the marine symbiotic actinobacteria Streptomyces caniferus GUA-06-05-006A. Structurally, PM100117 and PM100118 are composed of a macrocyclic lactone, three deoxysugar units and a naphthoquinone (NQ) chromophore that shows a clear structural similarity to menaquinone. RESULTS: Whole-genome sequencing of S. caniferus GUA-06-05-006A has enabled the identification of PM100117 and PM100118 biosynthesis gene cluster, which has been characterized on the basis of bioinformatics and genetic engineering data. The product of four genes shows high identity to proteins involved in the biosynthesis of menaquinone via futalosine. Deletion of one of these genes led to a decay in PM100117 and PM100118 production, and to the accumulation of several derivatives lacking NQ. Likewise, five additional genes have been genetically characterized to be involved in the biosynthesis of this moiety. Moreover, the generation of a mutant in a gene coding for a putative cytochrome P450 has led to the production of PM100117 and PM100118 structural analogues showing an enhanced in vitro cytotoxic activity relative to the parental products. CONCLUSIONS: Although a number of compounds structurally related to PM100117 and PM100118 has been discovered, this is, to our knowledge, the first insight reported into their biosynthesis. The structural resemblance of the NQ moiety to menaquinone, and the presence in the cluster of four putative menaquinone biosynthetic genes, suggests a connection between the biosynthesis pathways of both compounds. The availability of the PM100117 and PM100118 biosynthetic gene cluster will surely pave a way to the combinatorial engineering of more derivatives. PMID- 26905291 TI - Peer social interaction is facilitated in juvenile rhesus monkeys treated with fluoxetine. AB - Fluoxetine improves social interactions in children with autism, social anxiety and social phobia. It is not known whether this effect is mediated directly or indirectly by correcting the underlying pathology. Genetics may also influence the drug effect. Polymorphisms of the MAOA (monoamine oxidase A) gene interact with fluoxetine to influence metabolic profiles in juvenile monkeys. Juvenile nonhuman primates provide an appropriate model for studying fluoxetine effects and drug*gene interactions in children. Male rhesus monkeys 1-3 years of age living in permanent social pairs were treated daily with a therapeutic dose of fluoxetine or vehicle (n = 16/group). Both members of each social pair were assigned to the same treatment group. They were observed for social interactions with their familiar cagemate over a 2-year dosing period. Subjects were genotyped for MAOA variable number of tandem repeats (VNTR) polymorphisms categorized for high or low transcription rates (hi-MAOA, low-MAOA). Fluoxetine-treated animals spent 30% more time in social interaction than vehicle controls. Fluoxetine significantly increased the duration of quiet interactions, the most common type of interaction, and also of immature sexual behavior typical of rhesus in this age group. Specific behaviors affected depended on MAOA genotype of the animal and its social partner. When given fluoxetine, hi-MOAO monkeys had more social invitation and initiation behaviors and low-MAOA subjects with low-MAOA partners had more grooming and an increased frequency of some facial and vocal expressive behaviors. Fluoxetine may facilitate social interaction in children independent of remediation of psychopathology. Common genetic variants may modify this effect. PMID- 26905294 TI - Rebranding schizophrenia is unlikely to reduce stigma. PMID- 26905293 TI - The uncoupled ATPase activity of the ABC transporter BtuC2D2 leads to a hysteretic conformational change, conformational memory, and improved activity. AB - ABC transporters comprise a large and ubiquitous family of proteins. From bacteria to man they translocate solutes at the expense of ATP hydrolysis. Unlike other enzymes that use ATP as an energy source, ABC transporters are notorious for having high levels of basal ATPase activity: they hydrolyze ATP also in the absence of their substrate. It is unknown what are the effects of such prolonged and constant activity on the stability and function of ABC transporters or any other enzyme. Here we report that prolonged ATP hydrolysis is beneficial to the ABC transporter BtuC2D2. Using ATPase assays, surface plasmon resonance interaction experiments, and transport assays we observe that the constantly active transporter remains stable and functional for much longer than the idle one. Remarkably, during extended activity the transporter undergoes a slow conformational change (hysteresis) and gradually attains a hyperactive state in which it is more active than it was to begin with. This phenomenon is different from stabilization of enzymes by ligand binding: the hyperactive state is only reached through ATP hydrolysis, and not ATP binding. BtuC2D2 displays a strong conformational memory for this excited state, and takes hours to return to its basal state after catalysis terminates. PMID- 26905295 TI - Mitochondria and senescence: new actors for an old play. AB - Mitochondrial dysfunction has been linked to both cellular senescence and ageing. Despite the relationship, it is still unclear whether mitochondria have a causal role in senescence. In this issue of The EMBO Journal, Correia-Melo et al (2016) combine targeted depletion of mitochondria with impairment of their biogenesis to demonstrate that decreased numbers of mitochondria impair the senescence response. Their results suggest that targeting mitochondria could reduce the detrimental effects of senescence during ageing. PMID- 26905292 TI - Viral vectors for therapy of neurologic diseases. AB - Neurological disorders - disorders of the brain, spine and associated nerves - are a leading contributor to global disease burden with a shockingly large associated economic cost. Various treatment approaches - pharmaceutical medication, device-based therapy, physiotherapy, surgical intervention, among others - have been explored to alleviate the resulting extent of human suffering. In recent years, gene therapy using viral vectors - encoding a therapeutic gene or inhibitory RNA into a "gutted" viral capsid and supplying it to the nervous system - has emerged as a clinically viable option for therapy of brain disorders. In this Review, we provide an overview of the current state and advances in the field of viral vector-mediated gene therapy for neurological disorders. Vector tools and delivery methods have evolved considerably over recent years, with the goal of providing greater and safer genetic access to the central nervous system. Better etiological understanding of brain disorders has concurrently led to identification of improved therapeutic targets. We focus on the vector technology, as well as preclinical and clinical progress made thus far for brain cancer and various neurodegenerative and neurometabolic disorders, and point out the challenges and limitations that accompany this new medical modality. Finally, we explore the directions that neurological gene therapy is likely to evolve towards in the future. This article is part of the Special Issue entitled "Beyond small molecules for neurological disorders". PMID- 26905297 TI - The classic tarsorrhaphy of Anton Elschnig: 100 years later. PMID- 26905296 TI - Synthesis of triazole-linked morpholino oligonucleotides via Cu(I) catalysed cycloaddition. AB - Triazole-linked morpholino ((TL)MO) oligonucleic acids were synthesised using the Cu(I) catalysed (3 + 2) azide-alkyne cycloaddition (CuAAC) reaction. The modified DNA analogues were incorporated into 13-mer sequences via solid phase synthesis. UV melting experiments showed that the (TL)MO modification gives higher Tm values than the corresponding (TL)DNA modification. PMID- 26905298 TI - Severe Israeli spotted fever with multiorgan failure in a child. AB - An increased risk of severe and fatal Israeli spotted fever (ISF) has been observed in adults, mostly associated with ISF strain. Here, we report a case of severe ISF with multiorgan failure in a Portuguese child. PMID- 26905299 TI - Learning by listing: A content analysis of students' perceptions of older adults and grandparents. AB - Views of specific older adults may differ substantially from views of older adults in general, and such views may influence preconceived notions of aging that students bring into the classroom. Using an in-class activity, the authors tested the hypothesis that grandparents, about whom we know more individuated information, would be characterized by different, and more positive, descriptors than older adults. Following verbal prompts, undergraduates (N = 98) listed terms describing older adults and grandparents. Conventional and directed content analysis with a multistage coding scheme was employed. Results revealed that descriptors were primarily negative (e.g., sick) and emphasized physical characteristics (e.g., wrinkly) for older adults but were more positive (e.g., sweet) and highlighted personality characteristics (e.g., kind) for grandparents. Although mentioned less often for grandparents, health-related and physical characteristics were predominantly negative for both groups. This word-listing exercise highlighted heterogeneity in views of older adults and underscored the value of studying gerontology. PMID- 26905300 TI - Pharmacokinetic Investigation of Quetiapine Transport across Blood-Brain Barrier Mediated by Lipid Core Nanocapsules Using Brain Microdialysis in Rats. AB - Lipid-core nanocapsules (LCNs) have been proposed as drug carriers to improve brain delivery by modulating drug pharmacokinetics (PK). However, it is not clear whether the LCNs carry the drug through the blood-brain barrier or increase free drug penetration due to changes in the barrier permeability. Quetiapine (QTP) penetration to the brain is mediated by influx transporters and therefore might be reduced by drug transporters inhibitiors as probenecid. The goal of this work was to investigate the role of type-III LCNs on brain penetration of QTP using microdialysis in the presence probenecid. QTP-loaded LCN (QLNC) was successfully obtained with a small particle size (143 +/- 6 nm), low polydispersity index (PI < 0.1), and high encapsulation efficiency (95.4 +/- 1.82%.). Total and free drug concentration in plasma and free drug concentration in brain were analyzed following i.v. bolus dosing of nonencapsulated drug (FQ) and QLNC formulations alone and in association with probenecid to male Wistar rats. QTP free plasma fraction right after administration of QLNC was smaller than the fraction observed after FQ dosing; however, it increased over time until similar free drug levels were attained, suggesting that type-III LNCs produce a short in vivo sustained release of the drug. The inhibition of influx transporters by PB led to a reduction of free QTP brain penetration, as observed by the reduction of penetration factor from 1.55 +/- 0.17 to a value closer to unit (0.94 +/- 0.15). However, when the drug was nanoencapsulated, the inhibition of influx transporters had no effect on the brain penetration factor (0.88 +/- 0.21 to 0.92 +/- 0.13) probably because QTP is loaded into LNC and not available to interact with transporters. Taken together, these results suggest that LNC type-III carried QTP in the bloodstream and delivered the drug to the brain. PMID- 26905301 TI - Principal elementary mode analysis (PEMA). AB - Principal component analysis (PCA) has been widely applied in fluxomics to compress data into a few latent structures in order to simplify the identification of metabolic patterns. These latent structures lack a direct biological interpretation due to the intrinsic constraints associated with a PCA model. Here we introduce a new method that significantly improves the interpretability of the principal components with a direct link to metabolic pathways. This method, called principal elementary mode analysis (PEMA), establishes a bridge between a PCA-like model, aimed at explaining the maximum variance in flux data, and the set of elementary modes (EMs) of a metabolic network. It provides an easy way to identify metabolic patterns in large fluxomics datasets in terms of the simplest pathways of the organism metabolism. The results using a real metabolic model of Escherichia coli show the ability of PEMA to identify the EMs that generated the different simulated flux distributions. Actual flux data of E. coli and Pichia pastoris cultures confirm the results observed in the simulated study, providing a biologically meaningful model to explain flux data of both organisms in terms of the EM activation. The PEMA toolbox is freely available for non-commercial purposes on http://mseg.webs.upv.es. PMID- 26905302 TI - Neuroprotection of luteolin against methylmercury-induced toxicity in lobster cockroach Nauphoeta cinerea. AB - Luteolin (3', 4', 5, 7-tetrahydroxyflavone) is a polyphenolic compound found in foods of plant origin and has been reported to possess antioxidant and neuroprotective properties. However, there is dearth of information on the beneficial effects of luteolin on methylmercury (MeHg), a long-established neurotoxic compound in animals and humans. This study evaluated the effect of luteolin on MeHg-induced behavioral and biochemical deficits, using lobster cockroach Nauphoeta cinerea as an alternative and complementary animal model. The insects were exposed for 35 consecutive days to either MeHg alone (0.05 mg/g feed) or in combination with luteolin at 0.25, 0.5 and 1.0 mg/g feed. Locomotor behavior was assessed using video-tracking software during a 10-min trial in a novel arena and subsequently, biochemical analyses were carried out using the cockroaches' heads. Luteolin supplementation dose-dependently reversed the MeHg induced locomotor deficits and enhanced the exploratory profiles of MeHg-exposed cockroaches as confirmed by track and occupancy plot analyses. Luteolin reversed the MeHg-induced acetylcholinesterase activity inhibition, decreased dichlorofluorescein oxidation and lipid peroxidation levels, but increased total thiol level and catalase and glutathione S-transferase activities in the treated cockroaches. In conclusion, luteolin prevented oxidative stress indices and neurobehavioral deficits in a Nauphoeta cinerea model of MeHg toxicity. PMID- 26905303 TI - Repair of liver mediated by adult mouse liver neuro-glia antigen 2-positive progenitor cell transplantation in a mouse model of cirrhosis. AB - NG2-expressing cells are a population of periportal vascular stem/progenitors (MLpvNG2(+) cells) that were isolated from healthy adult mouse liver by using a "Percoll-Plate-Wait" procedure. We demonstrated that isolated cells are able to restore liver function after transplantation into a cirrhotic liver, and co localized with the pericyte marker (immunohistochemistry: PDGFR-beta) and CK19. Cells were positive for: stem cell (Sca-1, CD133, Dlk) and liver stem cell markers (EpCAM, CD14, CD24, CD49f); and negative for: hematopoietic (CD34, CD45) and endothelial markers (CD31, vWf, von Willebrand factor). Cells were transplanted (1 * 10(6) cells) in mice with diethylnitrosamine-induced cirrhosis at week 6. Cells showed increased hepatic associated gene expression of alpha fetoprotein (AFP), Albumin (Alb), Glucose-6-phosphatase (G6Pc), SRY (sex determining region Y)-box 9 (Sox9), hepatic nuclear factors (HNF1a, HNF1beta, HNF3beta, HNF4alpha, HNF6, Epithelial cell adhesion molecule (EpCAM), Leucine rich repeated-containing G-protein coupled receptor 5-positive (Lgr5) and Tyrosine aminotransferase (TAT). Cells showed decreased fibrogenesis, hepatic stellate cell infiltration, Kupffer cells and inflammatory cytokines. Liver function markers improved. In a cirrhotic liver environment, cells could differentiate into hepatic lineages. In addition, grafted MLpvNG2(+) cells could mobilize endogenous stem/progenitors to participate in liver repair. These results suggest that MLpvNG2(+) cells may be novel adult liver progenitors that participate in liver regeneration. PMID- 26905304 TI - The significance of anterior prostate lesions on multiparametric magnetic resonance imaging in African-American men. AB - INTRODUCTION: African-American (AA) men tend to harbor high-risk prostate cancer (PCa) and exhibit worse outcomes when compared to other groups. It has been postulated that AA men may harbor more anterior prostate lesions (APLs) that are undersampled by the standard transrectal ultrasound guided-biopsy (SBx), potentially resulting in greater degree of Gleason score (GS) upgrading at radical prostatectomy. We aimed to evaluate the detection rate of anterior PCa significance of APLs in AA men on multiparametric magnetic resonance imaging (mpMRI) and compare it to a matched cohort of White/Other (W/O) men. MATERIALS AND METHODS: A review of 1,267 men who had an mpMRI with suspicious prostate lesions and who underwent magnetic resonance transrectal ultrasound fusion-guided biopsy (FBx) with concurrent SBx in the same biopsy session was performed. All AA men were matched to a control group of W/O using a 1:1 propensity score-matching algorithm with age, prostate-specific antigen, and prostate volume as matching variables. Logistic regression analysis was used to determine predictors of APLs in AA men. RESULTS: Of the 195 AA men who underwent mpMRI, 93 (47.7%) men had a total of 109 APLs. Prior negative SBx was associated with the presence of APLs in AA men (Odds ratio = 1.81; 95% CI: 1.03-3.20; P = 0.04). On multivariate logistic regression analysis, smaller prostate (P = 0.001) and rising prostate-specific antigen (P = 0.007) were independent predictors of cancer-positive APLs in AA men. Comparative analysis of AA (93/195, 47.7%) vs. W/O (100/194, 52%) showed no difference in the rates of APLs (P = 0.44) or in cancer detection rate within those lesions or the distribution of GS within those cancers (P = 0.63) despite an overall higher cancer detection rate in AA men (AA: 124/195 [63.6%] vs. W/O: 97/194 [50.0%], P = 0.007). In cases where APLs were positive for PCa on FBx, the GS of APL was equal to the highest GS of the entire gland in 82.9% (29/35) and 90.9% (30/33) of the time in AA and W/O men, respectively. CONCLUSION: Cancer positive APLs represented the highest risk GS in most cases. AA men with prior negative SBx are twice as likely to harbor a concerning APL. In our cohort, AA and W/O men had comparable rates of APLs on mpMRI. Thus, differences in APLs do not explain the higher risk of AA men for deahth due to PCa. However, targeting of APLs via FBx can clinically improve PCa risk stratification and guide appropriate treatment options. PMID- 26905305 TI - Molecular orbital analysis of the hydrogen bonded water dimer. AB - As an essential interaction in nature, hydrogen bonding plays a crucial role in many material formations and biological processes, requiring deeper understanding. Here, using density functional theory and post-Hartree-Fock methods, we reveal two hydrogen bonding molecular orbitals crossing the hydrogen bond's O and H atoms in the water dimer. Energy decomposition analysis also shows a non-negligible contribution of the induction term. Our finding sheds light on the essential understanding of hydrogen bonding in ice, liquid water, functional materials and biological systems. PMID- 26905306 TI - Intracochlear Drug Injections through the Round Window Membrane: Measures to Improve Drug Retention. AB - The goal of this study was to develop an appropriate methodology to apply drugs quantitatively to the perilymph of the ear. Intratympanic applications of drugs to the inner ear often result in variable drug levels in the perilymph and can only be used for molecules that readily permeate the round window (RW) membrane. Direct intracochlear and intralabyrinthine application procedures for drugs, genes or cell-based therapies bypass the tight boundaries at the RW, oval window, otic capsule and the blood-labyrinth barrier. However, perforations can release inner ear pressure, allowing cerebrospinal fluid (CSF) to enter through the cochlear aqueduct, displacing the injected drug solution into the middle ear. Two markers, fluorescein or fluorescein isothiocyanate-labeled dextran, were used to quantify how much of an injected substance was retained in the cochlear perilymph following an intracochlear injection. We evaluated whether procedures to mitigate fluid leaks improved marker retention in perilymph. Almost all procedures to reduce volume efflux, including the use of gel for internal sealing and glue for external sealing of the injection site, resulted in improved retention of the marker in perilymph. Adhesive on the RW membrane effectively prevented leaks but also influenced fluid exchange between CSF and perilymph. We conclude that drugs can be delivered to the ear in a consistent, quantitative manner using intracochlear injections if care is taken to control the fluid leaks that result from cochlear perforation. PMID- 26905307 TI - Impact of Socioeconomic Status on the Diagnosis of Primary Open-Angle Glaucoma and Primary Angle Closure Glaucoma: A Nationwide Population-Based Study in Taiwan. AB - PURPOSE: To understand the impact of socioeconomic status (SES) on the diagnosis of primary open-angle glaucoma (POAG) and primary angle closure glaucoma (PACG) in Taiwan. METHODS: Subjects with glaucoma were identified from the National Health Insurance Research Database of year 2006, which included one million randomly selected insurants. Individuals who had >=4 ambulatory visits within one year which had the diagnosis code of POAG (ICD-9-CM 365.11 or 365.12) or PACG (365.23) and concurrent prescription of anti-glaucoma medication or surgery were selected. Individual SES was represented by monthly income calculated from the insurance premium. Neighborhood SES was defined based on neighborhood household income averages. Urbanization level of habitation was categorized into 3 levels. The odds ratio of having POAG or PACG in subjects with different SES was evaluated by using multiple logistic regression analysis. RESULTS: In total, 752 and 561 subjects with POAG and PACG, respectively, who were treated on a regular basis, were identified. The diagnosis of glaucoma was affected by age, gender, frequency of healthcare utilization, individual SES, and urbanization level of habitation. With the adjustment of age, gender, healthcare utilization, neighborhood SES and level of urbanization, subjects with lower income were more likely to be diagnosed as PACG, but less likely as POAG. CONCLUSIONS: Subjects with more frequent healthcare utilization were more likely to be diagnosed with glaucoma. Subjects with low SES were more susceptible to PACG, but subjects with high SES were more likely to be diagnosed as POAG. This information is useful for the design and target participant setting in glaucoma education and screening campaign to maximize the efficacy of limited resources in preventing glaucoma blindness. PMID- 26905308 TI - Expression analysis and association of RBBP6 with apoptosis in colon cancers. AB - Apoptosis is normally kept under strict control by a range of regulators and inhibitors, and loss of this regulation strongly directs tumour progression. The novel RBBP6 gene has been implicated in apoptosis due to its ability to bind both p53 and Rb, as well as its structural and functional affiliation to ubiquitin and E3 ligases. RBBP6 has already been implicated as an important marker for cancer diagnosis and many studies have investigated its suitability as a potential genetic target for cancer treatment. This study endeavoured to assess the transcription and expression patterns and levels of the three isoforms of RBBP6 in colon cancer and to evaluate its potential role in apoptosis. Colorimetric and fluorescent in situ hybridisation was used to localise the mRNA and the different RBBP6 mRNA transcripts in normal and cancerous colon tissue. Immunohistochemistry was used to localise different RBBP6 isoforms in normal and cancerous tissues. All the RBBP6 transcripts were found to be up-regulated in cancerous tissues, and the expression levels of the RBBP6-1 and RBBP6-3 (DWNN) proteins were also found to be increased in cancerous structures. Higher levels of apoptosis were detected in the same regions as those that showed increased expression of RBBP6-3 transcript and protein, whereas Bcl-2 was down-regulated in these areas. In contrast we observed an increase in Bcl-2 levels in areas where RBBP6-3 was down regulated. These results suggest that the RBBP6-3 isoform may be involved in promoting apoptosis in cancerous cells. PMID- 26905309 TI - Zygotic LvBMP5-8 is required for skeletal patterning and for left-right but not dorsal-ventral specification in the sea urchin embryo. AB - Skeletal patterning in the sea urchin embryo requires coordinated signaling between the pattern-dictating ectoderm and the skeletogenic primary mesenchyme cells (PMCs); recent studies have begun to uncover the molecular basis for this process. Using an unbiased RNA-Seq-based screen, we have previously identified the TGF-beta superfamily ligand, LvBMP5-8, as a skeletal patterning gene in Lytechinus variegatus embryos. This result is surprising, since both BMP5-8 and BMP2/4 ligands have been implicated in sea urchin dorsal-ventral (DV) and left right (LR) axis specification. Here, we demonstrate that zygotic LvBMP5-8 is required for normal skeletal patterning on the left side, as well as for normal PMC positioning during gastrulation. Zygotic LvBMP5-8 is required for expression of the left-side marker soxE, suggesting that LvBMP5-8 is required for left-side specification. Interestingly, we also find that LvBMP5-8 knockdown suppresses serotonergic neurogenesis on the left side. While LvBMP5-8 overexpression is sufficient to dorsalize embryos, we find that zygotic LvBMP5-8 is not required for normal DV specification or development. In addition, ectopic LvBMP5-8 does not dorsalize LvBMP2/4 morphant embryos, indicating that, in the absence of BMP2/4, BMP5-8 is insufficient to specify dorsal. Taken together, our data demonstrate that zygotic LvBMP5-8 signaling is essential for left-side specification, and for normal left-side skeletal and neural patterning, but not for DV specification. Thus, while both BMP2/4 and BMP5-8 regulate LR axis specification, BMP2/4 but not zygotic BMP5-8 regulates DV axis specification in sea urchin embryos. PMID- 26905310 TI - Maxillofacial fractures among Sudanese children at Khartoum Dental Teaching Hospital. AB - BACKGROUND: Maxillofacial fractures in children are less frequent compared to adults but result in special complications affecting the growth, function and esthetics. AIM: The study aimed at assessing the characteristics and the pattern of facial fractures among children seen at Khartoum Teaching Dental Hospital (KTDH). METHOD: The study included 390 patients presenting with maxillofacial trauma at KTDH during a year period (2010-2011). RESULTS: A total of 390 patients, diagnosed with facial fractures, were seen at KTDH; 14.1% (55) were children below 16 years of age with the mean age of 10 years (SD +/- 3.9). The ratio of males to females was 2.2:1. Most fractures were due to road traffic accidents (RTA) 56.4%, followed by daily living activities 21.8% and assault 16.4%. The most prevalent anatomic sites of fractures were mandible 77%; combination fractures i.e. more than one site 32.7% and zygomatic-complex (13.5%). Concomitant injuries were found in 9.1%. Almost half of the patients were managed conservatively 49.1%, closed reduction 34.5% and surgical open reduction 16.4%. CONCLUSIONS: The findings of this study indicated that pediatric facial fractures constitute 14.1% of the total number of facial fractures. RTA was the main cause, which should be considered in legislative and preventive strategies. PMID- 26905312 TI - Modulatory effects of methanol extract of Artocarpus altilis (Moraceae) on cadmium-induced hepatic and renal toxicity in male Wistar rats. AB - BACKGROUND: Cadmium (Cd) is an environmental risk factor with an established toxicity in animals. Therefore, natural antioxidants may be protective against Cd toxicity. The study was designed to investigate the modulatory effects of methanol extract of Artocarpus altilis (AA) on oxidant-antioxidant balance and lipid profile in liver and kidney of Cd-exposed rats while quercetin (QE) served as standard. METHODS: Total phenolic content (TPC) and 2,2-diphenyl-1 picryldydrazyl (DPPH) radical scavenging activity of AA were assessed in vitro. In vivo, rats were orally treated with AA (200mg/kg) and QE (25mg/kg) daily for three weeks and challenged with two doses of Cd (1.5mg/kg, i.p.) in the last 72h. RESULTS: The TPC and DPPH scavenging effects of AA were high and comparable with catechin. Cd-intoxication significantly (p<0.05) increased the activities of serum alanine aminotransferase and levels of urea, total bilirubin and creatinine by 94%, 60%, 234% and 76%, respectively. Cd-exposure caused a significant increase (p<0.05) in serum and tissues total cholesterol, triglyceride, low density lipoprotein-cholesterol and reduction in high-density lipoprotein cholesterol levels. The levels of hepatic and renal antioxidant parameters: glutathione-s-transferase, superoxide dismutase and reduced glutathione were significantly (p<0.05) decreased in Cd-intoxicated rats with concomitant elevation of lipid peroxidation. Histopathological findings revealed necrosis and distortion of architecture of renal tissue and, periportal infiltration in hepatocytes of Cd-intoxicated rats. Pretreatment with AA and QE restored antioxidant status, lipid profile and attenuated the lesions in the tissues. CONCLUSIONS: Extract of A. altilis protects against Cd-induced liver and kidney dysfunction via antioxidant and radical scavenging activities. PMID- 26905311 TI - Acute pancreatitis-induced thrombotic thrombocytopenic purpura with recurrent acute pancreatitis. AB - Recent successive reports on acute pancreatitis-induced thrombotic thrombocytopenic purpura (TTP) have revealed that TTP-related microvascular damage is an aggravating factor of acute pancreatitis. Here, we report the case of a 26-year-old man diagnosed with acute pancreatitis due to high alcohol consumption. The patient was unconscious as he had taken an overdose of medication, and presented with fever and renal failure due to acute pancreatitis on admission. Although the pancreatitis subsequently improved, the symptoms were still observed; on the next day, he exhibited hemoglobinuria, anemia, and thrombocytopenia. Moreover, general blood examinations indicated the presence of schistocytes and reduced activity of ADAMTS13 (a disintegrin-like metalloproteinase with thrombospondin type 1 motif 13) to 47 %. Thus, the patient was diagnosed with TTP, and plasma exchange was performed. After the development of TTP, the acute pancreatitis recurred, but a severe pathogenesis was prevented by plasma exchange. Thus, ADAMTS13 activity may be useful for predicting a severe pathogenesis of acute pancreatitis. In ADAMTS13-deficient cases, plasma exchange may be an effective technique for preventing aggravation of acute pancreatitis. PMID- 26905313 TI - HCS, an affordable instrument to assess haemoglobin. PMID- 26905314 TI - Accuracy of the WHO Haemoglobin Colour Scale for the diagnosis of anaemia in primary health care settings in low-income countries: a systematic review and meta-analysis. AB - BACKGROUND: Anaemia is a major cause of morbidity and mortality in low-income countries. Primary health-care workers in resource-poor settings usually diagnose anaemia clinically, but this is inaccurate. The WHO Haemoglobin Colour Scale (HCS) is a simple, cheap quantitative method to assess haemoglobin concentration outside of the laboratory. We systematically reviewed the literature to assess the accuracy of the HCS in primary care to diagnose anaemia, and compared this with clinical assessment. METHODS: We searched the electronic databases including MEDLINE, EMBASE, SCOPUS, Web of Science, Cochrane library, CINAHL plus, Popline, Reproductive Health Library, and Google Scholar and regional databases up to Nov 14, 2014, "haemoglobin colour scale" in alternative spellings published in any language. Two reviewers independently screened studies, extracted data, and assessed quality using the QUADAS-2 instrument. Statistical analyses were carried out in STATA using the bivariate model. FINDINGS: Of 141 records and abstracts screened, 14 studies were included. The pooled sensitivity of the HCS to diagnose anaemia was 80% (95% CI 68-88) compared with 52% for clinical assessment ([95% CI 36-67]; p=0.008). Specificity was similar between the HCS (80% [95% CI 59-91]) and clinical assessment (75% [56-88]; p=0.8250). For severe anaemia, diagnostic accuracy was again higher overall for the HCS (p<0.0001); sensitivity was 57% (36 76) for the HCS and 45% (95% CI 12-83) for clinical assessment, but specificity was 99.6% (95% CI 95-99.9) versus 92% (62-99). Combining clinical assessment and the HCS could result in higher sensitivity (anaemia: 91% [95% CI 81-96]); severe anaemia 83% (33-98), but at the expense of specificity (anaemia: 59% [35-79]; severe anaemia 90% [40-99]). Individual studies were highly heterogeneous but pooled results did not differ substantially in a series of sensitivity analyses for indicators of study robustness. INTERPRETATION: In so-called real-life primary health-care conditions, HCS can significantly reduce misdiagnosis of anaemia compared with clinical assessment alone. Future research is required to optimise training, and assess clinical outcomes and cost-effectiveness. FUNDING: None. PMID- 26905315 TI - Influence of Alternative Exposure Estimates in the Diesel Exhaust Miners Study: Diesel Exhaust and Lung Cancer. AB - The landmark Diesel Exhaust in Miners Study (DEMS) studied the relationship between diesel exhaust exposure (DEE) and lung cancer mortality of workers at eight nonmetal mines who were followed from beginning of dieselization of the mines (1947-1967) through December 31, 1997. The original analyses quantified DEE exposures using exposure to respirable elemental carbon (REC) to represent DEE, and CO as a surrogate for REC. However, this use of CO data, and the CO data themselves, have numerous shortcomings. We developed new estimates of REC exposures using historical data on use of diesel equipment, diesel engine horsepower (HP), mine ventilation rates, and the documented reduction in particulate matter emissions per HP in diesel engines from 1975 through 1995. These new REC estimates were applied in a conditional logistic regression of the DEMS nested case-control data very similar to the one applied in the original DEMS analyses. None of the trend slopes calculated using the new REC estimates were statistically significant (p > 0.05). Moreover, these trend slopes were smaller by roughly factors of five without control for radon exposure and factors of 12 with control for radon exposure compared to those estimated in the original DEMS analyses. Also, the 95% confidence intervals for these trend slopes had only minimal overlap with those for the slopes in the original DEMS analyses. These results underscore the uncertainty in estimates of the potency of diesel exhaust in causing lung cancer based on analysis of the DEMS data due to uncertainty in estimates of exposures to diesel exhaust. PMID- 26905316 TI - Examining the dynamic relationships between exposure tasks and cognitive restructuring in CBT for SAD: Outcomes and moderating influences. AB - Meta-analyses indicate that cognitive behavioral therapy (CBT) for social anxiety disorder (SAD) leads to substantial symptom alleviation. Although there is an emphasis on engaging in exposure and cognitive restructuring during treatment, the longitudinal relationship between skill use and symptom alleviation is not well understood. Furthermore, treatment response may be attenuated by pre existing patient vulnerabilities. This study examined the longitudinal association of skill use (i.e. exposure (EX), thought record use (TR)), symptom reduction and the potential moderating influence of perfectionism during a 12 session, manual-based CBT for SAD intervention for 100 patients (51% female) meeting DSM-IV criteria for SAD. Results obtained from Latent Difference Score (LDS) models indicated that the frequency of both EX and TR skill use led to subsequent symptom alleviation; however, this varied based on the type of skill used. Further, although both EX and TR interventions were associated with subsequent symptom reduction, the association of EX and subsequent symptom alleviation was greater than the association of TR and subsequent symptom alleviation. Finally, higher pre-treatment perfectionism was associated with greater initial skill use, followed by significantly reduced skill use in later sessions. These preliminary results suggest that perfectionistic individuals demonstrate differential engagement in EX and TR interventions during treatment. PMID- 26905317 TI - Comparison of survival, safety, and efficacy after transarterial chemoembolization and radioembolization of Barcelona Clinic Liver Cancer stage B C hepatocellular cancer patients. AB - AIM: This study aimed to compare the overall survival (OS) times, long-term complications, and recurrence rates of chemoembolization and radioembolization for Barcelona Clinic Liver Cancer (BCLC) stage B-C hepatocellular cancer patients. MATERIALS AND METHODS: This retrospective study included 80 BCLC stage B-C hepatocellular cancer patients who received chemoembolization (group 1) or radioembolization (group 2). The OS times, long-term complications, and disease recurrence rates of the two groups were compared. The prognostic role of sex, age, presence of underlying chronic liver disease, BCLC stage, dimension and number of liver lesions, tumor load, and presence of extrahepatic disease were also analyzed for each group. RESULTS: Each group included 40 (67 men, 13 women, mean age: 41.9+/-21.9 years) patients. During the follow-up period, 22 patients died in group 2 and 30 patients died in group 1. The overall mean survival of the entire patient group was calculated to be 37.31+/-3.94 months [95% confidence interval (CI), 30.46-44.1 months], with 30.63+/-3.68 months (95% CI, 23.42-37.84 months) for group 1 and 39.24+/-4.62 months (95% CI, 30.18-48.29 months) for group 2 (P=0.014). The 1- and 2-year survival rates were 72 versus 74% and 47 versus 59% for groups 2 and 1, respectively. There was no significant difference between the chronic complication (P=0.32) and disease recurrence (P=0.65) rates of the groups. Whereas the dimension of the largest lesion was the most significant predictor (P=0.01) in group 2, female sex (P=0.008), dimension of the largest lesion (P=0.03), and BCLC stage (P=0.01) were significant in group 1. CONCLUSION: Although chemoembolization and radioembolization for BCLC Stage B-C patients have similar levels of safety and efficacy, they differ in OS. In this retrospective study, patients undergoing radioembolization had a longer survival rate. PMID- 26905318 TI - Preparation of Gold-Carbon Dots and Ratiometric Fluorescence Cellular Imaging. AB - In this study, we synthesized novel gold-carbon dots (GCDs) with unique properties by microwave-assisted method. The characterization of high-resolution transmission electron microscope (HRTEM), XRD, high-angle annular dark field scanning transmission electron microscope (HAADF-STEM), and energy dispersive spectrometer demonstrates that GCDs are composed of carbon and Au. Tiny Au clusters are dispersed in a 2 nm-size carbon skeleton, which integrates the properties of typical CDs and gold nanoclusters (AuNCs), displaying fascinating peroxidase-like activity and single excitation/dual emission. Dual emission of the GCDs exhibits different fluorescent response to the target species and enables the GCDs to be exploited for sensing and bioimaging. The highly photostable and biocompatible GCDs were applied to dual fluorescent imaging for breast cancer cells and normal rat osteoblast cells under a single excitation. Moreover, ratiometric fluorescence imaging was used to monitor Fe(3+) level in normal rat osteoblast cells. PMID- 26905319 TI - Characteristics of anti-hepatitis C virus antibody-positive patients in a hospital setting in Douala, Cameroon. AB - INTRODUCTION: Hepatitis C virus (HCV) infection is a major public health problem, especially in resource-limited settings where many patients are diagnosed at the stage of complications. In Cameroon, where HCV is endemic, little is known about the clinical, biological, and virological profile of HCV-infected patients. METHODS: A clinical case note review of all patients positive for antibodies against HCV diagnosed at the gastroenterology outpatient clinic of the Douala General Hospital, Cameroon, from January 2008 to December 2014, was performed. RESULTS: A total of 524 patients were included in the study, 53% of whom were female. The mean age was 56+/-13 years. A history of blood transfusion and a history of scarification were the most common potential risk factors for HCV exposure, as found in 16% and 13% of the study population, respectively. Current alcohol use was found in 24% of patients. Co-infection with hepatitis B virus and HIV was 3.6% and 3.4%, respectively. Among the patients, 39% had no complaint at diagnosis; only 16% were diagnosed through a routine medical checkup. Clinically, the most common finding was hepatomegaly (26.1% of patients). Transaminases above the upper limit of normal were found in 55.2% of patients, particularly those aged >57 years (p=0.001). Genotypes 1 (43.95%), 2 (25.11%), and 4 (28.25%) were the most common. Liver cirrhosis was present in 11% of patients and hepatocellular carcinoma in 4%, the latter being more common in males (p<0.001) and in those aged >57 years (p=0.03). CONCLUSIONS: In the gastroenterology clinic of Douala General Hospital, while almost 40% of patients who were anti-HCV antibody-positive were asymptomatic and diagnosed fortuitously, some already presented complications, including cirrhosis and hepatocellular carcinoma. There is an urgent need to put in place programs to increase awareness and diagnosis of HCV infection and to develop extensive and targeted anti-HCV treatment guidelines to improve the management of these patients in Cameroon. PMID- 26905320 TI - Is there a relationship between hypomagnesemia and proton-pump inhibitors in patients on chronic hemodialysis? AB - AIM: We investigated the association among long-term proton-pump inhibitors (PPIs) use with serum magnesium (Mg) levels in chronic hemodialysis (HD) patients, as well as possible association among PPI use and increased risk of cardiovascular (CVD) morbidity in HD patients. METHODS: Of 418 HD patients that were screened for inclusion, 136 were excluded due to incomplete medical data, duration of renal replacement therapy (RRT) for less than 12months, use of Mg based-phosphate binders or other Mg-based medications or either to presence of chronic increased GI losses. Among 282 patients included in the study, 170 patients were on PPIs. RESULTS: Serum Mg levels were significantly lower among PPI users vs. non-users (0.94+/-0.2 vs. 1.03+/-0.2mmol/L; p<0.0001). The median duration of PPI use was 27+/-9.6months (range from 12 to 108) and it was not significantly associated with Mg levels (r=0.116; p=0.167). Additionally, residual renal function didn't show a significant correlation with Mg concentration (r=-0.102; p=NS) in both groups of patients. The use of PPIs was an independent and strong predictor of low Mg concentrations even in multivariate analysis (OR 3.05; 95% CI 1.2498-7.4594, p=0.01). On the other hand, the daily dose of PPIs was not associated with low Mg levels. PPI users had a higher rate of adverse CVD events during the 1 year of follow-up in comparison to non-PPI users but that difference wasn't statistically significant (17.6% vs. 10.7%; p=0.110). CONCLUSION: We have found a significant association between PPI use and lower serum Mg levels in chronic HD patients. PMID- 26905321 TI - Transient ST-segment elevation during acute pancreatitis. PMID- 26905322 TI - Acute right iliac fossa pain: Beyond appendicitis. PMID- 26905323 TI - Effects of long-term pre- and post-natal exposure to 2.45 GHz wireless devices on developing male rat kidney. AB - PURPOSE: The aim of the present study was to investigate oxidative stress and apoptosis in kidney tissues of male Wistar rats that pre- and postnatally exposed to wireless electromagnetic field (EMF) with an internet frequency of 2.45 GHz for a long time. METHODS: The study was conducted in three groups of rats which were pre-natal, post-natal. and sham exposed groups. Oxidative stress markers and histological evaluation of kidney tissues were studied. RESULTS: Renal tissue malondialdehyde (MDA) and total oxidant (TOS) levels of pre-natal group were high and total antioxidant (TAS) and superoxide dismutase (SOD) levels were low. Spot urine NAG/creatinine ratio was significantly higher in pre- and post-natal groups (p < 0.001). Tubular injury was detected in most of the specimens in post-natal groups. Immunohistochemical analysis showed low-intensity staining with Bax in cortex, high-intensity staining with Bcl-2 in cortical and medullar areas of pre natal group (p values, 0.000, 0.002, 0.000, respectively) when compared with sham group. Bcl2/Bax staining intensity ratios of medullar and cortical area was higher in pre-natal group than sham group (p = 0.018, p = 0.011). CONCLUSION: Based on this study, it is thought that chronic pre- and post-natal period exposure to wireless internet frequency of EMF may cause chronic kidney damages; staying away from EMF source in especially pregnancy and early childhood period may reduce negative effects of exposure on kidney. PMID- 26905324 TI - Understanding dissemination of Mycobacterium tuberculosis from the lungs during primary infection. AB - Understanding how inhaled Mycobacterium tuberculosis achieves dramatic replication and crosses the alveolar barrier to establish systemic latent infection, before adaptive immunity is elicited in humans, is limited by the small infecting inoculum carried in aerosol droplets (1-5 MUm diameter) and the inability to identify the time of infection. M. tuberculosis is believed to disseminate via infected macrophages. However, like other invasive bacterial pathogens, M. tuberculosis could also cross the barrier directly using adhesins and toxins. An in vitro alveolar barrier mimicking the gas-exchange regions of the alveolus was devised comprising monolayers of human alveolar epithelial and endothelial cells cultured on opposing sides of a basement membrane. Migration of dissemination-competent strains of M. tuberculosis, and dissemination-attenuated M. tuberculosis and Mycobacterium bovis mutant strains lacking adhesin/toxin ESAT 6 and adhesin HBHA were tested for macrophage-free migration across the barrier. Strains that disseminate similarly in vivo migrated similarly across the in vitro alveolar barrier. Strains lacking ESAT-6 expression/secretion were attenuated, and absence of both ESAT-6 and HBHA increased attenuation of bacterial migration across the barrier. Thus, as reported for other bacteria, M. tuberculosis utilizes adhesins and toxins for macrophage-independent crossing of the alveolar barrier. This in vitro model will allow identification and characterization of molecules/mechanisms employed by M. tuberculosis to establish systemic latent tuberculosis infection during primary infection. PMID- 26905326 TI - Poly(ADP-Ribose) Polymerase in Cervical Cancer Pathogenesis: Mechanism and Potential Role for PARP Inhibitors. AB - Treatment options for disease recurrence of women treated for locally advanced and advanced cervical cancer are very limited-largely palliative chemotherapy. The low efficacy of the currently available drugs raises the need for new targeted agents. Poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors (PARPi) have emerged as a promising class of chemotherapeutic agents in cancers associated with defects in DNA repair. Their therapeutic potential in cervical cancer is currently being evaluated in 3 ongoing clinical trials. Here we review the available information regarding all the aspects of PARP in cervical intraepithelial neoplasia and invasive cervical cancer, from expression and the mechanism of action to the role of the polymorphisms in the pathogenesis of the disease, as well as the potential of the inhibitors. We finally propose a new unifying theory regarding the role of PARPs in the development of cervical carcinomas. PMID- 26905325 TI - Enhanced denitrification of Pseudomonas stutzeri by a bioelectrochemical system assisted with solid-phase humin. AB - The denitrification reactions performed by Pseudomonas stutzeri JCM20778 were enhanced electrochemically with the use of solid-phase humin, although P. stutzeri itself was incapable of receiving electrons directly from the graphite electrode. Electrochemically reduced humin enhanced the microbial, but not abiotic, denitrification reactions. Electric current and cyclic voltammetry analyses suggested that the solid-phase humin functioned as an electron donor for the denitrification reactions of P. stutzeri. Nitrogen balance study and the estimation of the first-order rate constants of the consecutive denitrification reactions suggested that the solid-phase humin enhanced all reducing reactions from nitrate to nitrogen gas. Considering the wide distribution of humin in the environment, the findings that solid-phase humin can assist in electron transfer, from the electrode to a denitrifying bacterium that has little ability to directly utilize external electrons, has important implications for the widespread application of bioelectrochemical systems assisted by solid-phase humin for enhancing microbial denitrification. PMID- 26905327 TI - Neoadjuvant Chemotherapy Followed by Chemoradiation in Cervical Carcinoma: A Review. AB - OBJECTIVE: Cervical cancer is a public health problem. A large proportion of patients have locally advanced (LA) disease at presentation and for this group, neoadjuvant chemotherapy (NACT) has an undefined role in the era of chemoradiotherapy. In countries with restricted access to radiotherapy, NACT may precipitate patients' access to an effective treatment approach. We carried out a systematic review to evaluate available data about NACT followed by chemoradiation. METHODS: Studies evaluated the use of NACT followed by chemoradiotherapy. Search strategy was performed in MEDLINE, LILACS, and Cochrane Library from 2003 to 2013. Conference proceedings of American Society of Clinical Oncology annual meeting, International Journal of Gynecological Cancer Society biennial meeting, and European Society of Gynecological Oncology biennial meeting were also reviewed. Key words used were "cervical uterine cancer," "cervical uterine neoplasm," "neoadjuvant therapy," "neoadjuvant treatment," and "locally advanced." Data collected included author information, year of publication, study design, number of participants, eligibility criteria, treatment, response rate (RR), disease-free survival, overall survival, and toxicities. RESULTS: Initial searches retrieved 7670 references. There were 7 eligible trials. Only 2 studies were published and a total of 323 participants were recruited. Patients with LA disease were eligible in most of them. Neoadjuvant chemotherapy consisted of paclitaxel combined with a platinum compound. Compliance was more than 90% in published trials. Response rate to NACT ranged from 67.8% to 70%. Major toxicity was hematological. Survival was evaluated in different points in time. Overall survival was up to 93% in 2 years, and in a poor prognostic group, 81% of patients were alive after 22 months. However, we must interpret these results with caution because of data limitation. CONCLUSIONS: Our result raises the possibility of NACT as an alternative upfront treatment for these patients with a small risk of disease progression. In countries where radiotherapy network is limited, randomized clinical trials should clarify its role. PMID- 26905328 TI - Phosphatase and Tensin Homolog Is a Potential Target for Ovarian Cancer Sensitization to Cytotoxic Agents. AB - OBJECTIVES: The phosphatase and tensin homolog (PTEN) tumor suppressor protein has been found to be inactivated or mutated in various human malignancies and to play a role in cisplatin and poly(ADP-ribose) polymerase inhibitor sensitivity. In this study, we assessed the association of PTEN loss with homologous recombination (HR) deficiency and increased chemosensitivity. MATERIALS AND METHODS: The PTEN knockdown models were created using MISSION shRNA lentiviral transduction particles in cell lines derived from normal ovarian surface epithelium and a mixed endometrioid/clear-cell carcinoma. Sensitivity to common therapeutics was assessed using sulforhodamine B assay. Twenty-eight unselected primary epithelial ovarian cancer cultures derived from ascitic fluid collected at the time of surgery and matched genomic DNA were assessed for PTEN mutations using polymerase chain reaction amplification and Sanger sequencing and for mRNA expression using quantitative reverse transcription-polymerase chain reaction; HR was determined using gammaH2AX/RAD51 assay. The Cancer Genome Atlas data were analyzed using cBioPortal. RESULTS: In the carcinoma cell line, the PTEN knockdown enhanced sensitivity to cisplatin, rucaparib, doxorubicin, camptothecin, paclitaxel, and irradiation. In the primary ovarian cancer cultures, 2 point mutations were found (1105T>TG, 25L>L in 6 cultures and 1508G>GA, 159R>R in 4 cultures). The PTEN mRNA expression varied over 40-fold between the cultures, but did not correlate with HR status or in vitro sensitivity to cisplatin or rucaparib. The Cancer Genome Atlas data showed a rate of 8% alteration in PTEN and a trend toward improved survival in PTEN-mutated cases. CONCLUSIONS: These data indicate that although PTEN mutations in ovarian cancer are rare, PTEN inhibition results in therapeutic sensitization. Therefore, PTEN may be an important therapeutic target, in at least some cancers. PMID- 26905329 TI - Health-Related Quality of Life and Sociodemographic Characteristics as Prognostic Indicators of Long-term Survival in Disease-Free Cervical Cancer Survivors. AB - OBJECTIVES: Health-related quality-of-life (HRQOL) issues of cancer patients are considered an important clinical outcome. We aimed to investigate the prognostic value of HRQOL on long-term survival outcomes in disease-free cervical cancer survivors (CCSs). METHODS: The study sample consisted of 860 disease-free CCSs from 6 Korean cancer hospitals recruited for HRQOL survey during 2005 (median time from diagnosis, 5.9 years). Health-related quality-of-life measures included the European Organization for Research and Treatment of Cancer QLQ-C30 and its Cervical Cancer Module (CX24). Survival data were retrieved from the Korean Statistical Office after 6 years from the survey. Health-related quality-of-life domains along with sociodemographic and clinicopathologic variables were analyzed as prognostic factors for survival from the date of survey. RESULTS: During the median follow-up period of 6.3 years after the survey, 30 (3.5%) patients died from all causes. Age, time since diagnosis, and physical activity were independent prognostic factors, which constituted the baseline model along with cancer stage. When HRQOL domains were tested separately against the baseline model, functional scales (physical, role, social, and emotional functioning), global health status, symptom scales (pain and appetite loss), and cervical cancer module items (body image, sexual inactivity, and sexual worry) were significantly associated with survival (P < 0.05). CONCLUSIONS: These findings suggest that, in addition to well-known prognostic factors, including age, time since diagnosis, and physical activity, HRQOL scores obtained from disease-free CCSs are associated with survival. PMID- 26905330 TI - Safety and Efficacy of Neoadjuvant Chemotherapy Followed by Radical Surgery Versus Radical Surgery Alone in Locally Advanced Cervical Cancer Patients. AB - OBJECTIVES: This study aimed to evaluate the safety and efficacy of neoadjuvant chemotherapy (NACT) followed by radical surgery (RS) among patients with locally advanced cervical cancer (LACC). METHODS: Eight hundred patients with LACC received either NACT followed by RS (NACT-RS) or RS alone. The primary outcome measures assessed the efficacy and adverse effects of NACT. Secondary outcome measures compared the preoperative clinical stage to the postoperative pathologic stage in NACT-RS and RS patients, assessed intraoperative and postoperative complications, including the adverse effects of postoperative radiotherapy and radiochemotherapy, and estimated the 5-year progression-free survival and 5-year overall survival. RESULTS: The clinical response to NACT was 89.54%. Patients in the NACT-RS group had lower preoperative hemoglobin levels (115.20 vs 122.04 g/L, P < 0.001), a longer operative time (mean, 233.66 vs 224.37 minutes, P = 0.008), more intraoperative bleeding (750.34 vs 684.41 mL, P = 0.011), a shorter duration of catheter use (mean, 29.84 vs 32.14 days, P = 0.036), and a lower incidence of postoperative complications (7.30% vs 13.62%, P = 0.002) and postoperative radiotherapeutic and radiochemotherapeutic adverse effects (3.16% vs 4.63%, P < 0.001) compared to patients in the RS group. The 5-year progression-free survival and 5-year overall survival were 80.30% and 81.10% in the NACT-RS group and 81.00% and 78.50% in the RS group (P > 0.05). Pathological poor differentiation, nonsquamous cell carcinoma, parametrial invasion, positive pelvic lymph node, and lymphovascular invasion (P < 0.05) were independent risk factors for recurrence. CONCLUSIONS: Neoadjuvant chemotherapy may reduce RS-associated complications and postoperative radiotherapeutic and radiochemotherapeutic adverse effects in Chinese patients with LACC. PMID- 26905331 TI - Combined Immunoscore of CD103 and CD3 Identifies Long-Term Survivors in High Grade Serous Ovarian Cancer. AB - OBJECTIVE: Increased numbers of tumor-infiltrating lymphocytes (TILs) in high grade serous ovarian cancer (HGSC) are associated with improved clinical outcome. Intraepithelial localization of TILs might be regulated by specific homing receptors, such as CD103, which is widely expressed by intraepithelial lymphocytes. Given the emerging role of CD103 TILs, we aimed to assess their contribution to the prognostic value of immunoscoring in HGSC. METHODS: The density of intratumoral CD3 and CD103 lymphocytes was examined by immunohistochemistry on a tissue microarray of a series of 135 patients with advanced HGSC and correlated with CD4, CD8, CD56, FoxP3, and TCRgamma T-cell counts, as well as E-cadherin staining and conventional prognostic parameters and clinical outcome. RESULTS: Both the presence of CD103 cells, as well as high numbers of intraepithelial CD3 lymphocytes (CD3E), showed a significant correlation with overall survival, in the complete series, as well as in patients with optimal debulking and/or platinum sensitivity. Combining CD3 and CD103 counts improved prognostication and identified 3 major subgroups with respect to overall survival. The most pronounced effect was demonstrated for patients with optimally resected and platinum-sensitive tumors. Patients with CD3/CD103 tumors showed a 5-year survival rate at 90%, CD3/CD103 at 63%, and CD3/CD103 at 0% (P < 0.001). CONCLUSIONS: These results suggest that combined assessment of CD103 and CD3 counts improves the prognostic value of TIL counts in HGSC and might identify patients with early relapse or long-term survival based on the type and extent of the immune response. PMID- 26905332 TI - Pulmonary Resection in the Management of High-Risk Gestational Trophoblastic Neoplasia. AB - OBJECTIVE: The aim of this study was to evaluate the role of pulmonary resection in the management of high-risk gestational trophoblastic neoplasia (GTN). METHODS: Patients who underwent pulmonary resection as part of their treatment for chemotherapy-resistant high-risk GTN from 1986 and 2014 were retrospectively analyzed. All patients had received 1 or more multiagent chemotherapy regimens preoperatively. Patient and disease characteristics were evaluated with respect to outcome. RESULTS: Fifteen (26%) of 58 patients treated for high-risk GTN underwent pulmonary resection with curative intent. Mean age of patients was 29 years (range, 19-37 years). International Federation of Gynecology and Obstetrics stage was III in 12 and IV in 3. International Federation of Gynecology and Obstetrics scores ranged from 5 to 20 (mean, 10). Antecedent pregnancy was nonmolar in 11 patients (73%). Adjuvant surgical procedures other than pulmonary resection were performed in 8 patients (53%). Preoperative chemotherapy regimens ranged from 1 to 10 (median, 4) and courses numbered from 2 to 32 (median, 14). Preoperative human chorionic gonadotropin (hCG) levels ranged from 2 to 2786 mIU/mL (median, 177 mIU/mL). Pulmonary wedge resections or lobectomies were performed via video-assisted thoracoscopic surgery (11) or thoracotomy (4). Two patients underwent pulmonary resections on 2 separate occasions. No patient had complications as a result of these procedures. Eleven patients (73%) were cured. In these 11 patients, hCG levels decreased to less than 2 mIU/mL within 6 to 52 days (mean, 22 days) postoperatively. CONCLUSIONS: Pulmonary resection of chemotherapy-resistant GTN was an important component of treatment in 26% of high risk patients, 73% of whom were cured. Ideal candidates have disease isolated to the lungs and low hCG levels. PMID- 26905333 TI - Management of Endometrial Hyperplasia With a Levonorgestrel-Releasing Intrauterine System: A Korean Gynecologic-Oncology Group Study. AB - OBJECTIVE: The aim of the study was to evaluate the efficacy of the levonorgestrel intrauterine system (LNG-IUS) for treatment of endometrial hyperplasia (EH). METHODS: A prospective multicenter study was conducted from November 2010 to March 2014. Patients with histologically confirmed EH were treated with LNG-IUS. At 3, 6, and 9 months after LNG-IUS insertion, follow-up endometrial aspiration biopsies with the LNG-IUS in the uterus were undertaken. At the 12th month of follow-up, endometrial tissues were obtained via 2 methods: endometrial aspiration biopsy with the LNG-IUS in the uterus, followed by dilatation and curettage (D&C) after LNG-IUS removal. The primary outcome was the regression rate at 12 months after LNG-IUS insertion, and the secondary outcome was the consistency of the results between the endometrial aspiration biopsy and the D&C. RESULTS: The study population comprised 75 patients, including 37 with simple hyperplasia without atypia; 3 with atypical simple hyperplasia; 23 with complex hyperplasia without atypia, and 12 with atypical complex hyperplasia. Of these patients treated with the LNG-IUS, 38 (50.7%) were followed up at 12 months after LNG-IUS insertion. The complete regression rate at 12 months was 94.7% (36/38): 100% (6/6) of patients with atypical EH and 93.7% (30/32) with EH without atypia. In all of the cases (100%, 36/36), patients achieved complete regression within 3 months of LNG-IUS insertion. A comparison of the pathologic results from endometrial aspiration biopsy and D&C was carried out for 15 patients. In the histologic results by endometrial aspiration biopsy, 14 patients were diagnosed as "normal endometrium" and 1 as "insufficient tissue for pathologic evaluation." Among the 14 cases of normal endometrium by endometrial aspiration biopsy, 1 was diagnosed as "residual EH" by D&C, and the 1 case with insufficient tissue was diagnosed as normal endometrium by D&C. CONCLUSIONS: Levonorgestrel intrauterine system is an effective and favorable method for treatment of EH. PMID- 26905334 TI - The Novel IkappaB Kinase beta Inhibitor, IMD-0560, Has Potent Therapeutic Efficacy in Ovarian Cancer Xenograft Model Mice. AB - OBJECTIVE: Aberrant activation of nuclear factor-kappa beta (NF-kappaB) signaling has been correlated with poor outcome among patients with ovarian cancer. Although the therapeutic potential of NF-kappaB pathway disruption in cancers has been extensively studied, most classical NF-kappaB inhibitors are poorly selective, exhibit off-target effects, and have failed to be applied in clinical use. IMD-0560, N-[2,5-bis (trifluoromethyl) phenyl]-5-bromo-2-hydroxybenzamide, is a novel low-molecular-weight compound that selectively inhibits the IkappaB kinase complex and works as an inhibitor of NF-kappaB signaling. The aim of this study was to assess the therapeutic potential of IMD-0560 against ovarian cancer in vitro and in vivo. METHODS: NF-kappaB activity (phosphorylation) was determined in 9 ovarian cancer cell lines and the inhibitory effect of IMD-0560 on NF-kappaB activation was analyzed by Western blotting. Cell viability, cell cycle, vascular endothelial growth factor (VEGF) expression, and angiogenesis were assessed in vitro to evaluate the effect of IMD-0560 on ovarian cancer cells. In vivo efficacy of IMD-0560 was also investigated using an ovarian cancer xenograft mouse model. RESULTS: The NF-kappaB signaling pathway was constitutively activated in 8 of 9 ovarian cancer cell lines. IMD-0560 inhibited NF-kappaB activation and suppressed ovarian cancer cell proliferation by inducing G1 phase arrest. IMD-0560 decreased VEGF secretion from cancer cells and inhibited the tube formation of human umbilical vein endothelial cells. IMD-0560 significantly inhibited peritoneal metastasis and prolonged the survival in an ovarian cancer xenograft mice model. Immunohistochemical staining of excised tumors revealed that IMD-0560 suppressed VEGF expression, tumor angiogenesis, and cancer cell proliferation. CONCLUSIONS: IMD-0560 showed promising therapeutic efficacy against ovarian cancer xenograft mice by inducing cell cycle arrest and suppressing VEGF production from cancer cells. IMD-0560 may be a potential future option in regimens for the treatment of ovarian cancer. PMID- 26905335 TI - Changing Trends in the Clinical Presentation and Management of Complete Hydatidiform Mole Among Brazilian Women. AB - OBJECTIVE: The aim of the study was to evaluate potential changes in the clinical, diagnostic, and therapeutic parameters of complete hydatidiform mole in the last 25 years in Brazil. METHODS: A retrospective cohort study was conducted involving the analysis of 2163 medical records of patients diagnosed with complete hydatidiform mole who received treatment at the Rio de Janeiro Reference Center for Gestational Trophoblastic Disease between January 1988 and December 2012. For the statistical analysis of the natural history of the patients with complete molar pregnancies, time series were evaluated using the Cox-Stuart test and adjusted by linear regression models. RESULTS: A downward linear temporal trend was observed for gestational age of complete hydatidiform mole at diagnosis, which is also reflected in the reduced occurrence of vaginal bleeding, hyperemesis and pre-eclampsia. We also observed an increase in the use of uterine vacuum aspiration to treat molar pregnancy. Although the duration of postmolar follow-up was found to decline, this was not accompanied by any alteration in the time to remission of the disease or its progression to gestational trophoblastic neoplasia. CONCLUSIONS: Early diagnosis of complete hydatidiform mole has altered the natural history of molar pregnancy, especially with a reduction in classical clinical symptoms. However, early diagnosis has not resulted in a reduction in the development of gestational trophoblastic neoplasia, a dilemma that still challenges professionals working with gestational trophoblastic disease. PMID- 26905336 TI - Significance of the Factors Associated With Parametrial Involvement in Stage IB to IIA Cervical Cancer. AB - OBJECTIVE: The aim was to explore the factors associated with parametrial involvement (PI) in patients with stage IB to IIA cervical cancer. MATERIALS AND METHODS: Medical records of 507 patients were reviewed. Nine factors were analyzed by univariate analysis using chi test and multivariate analysis using logistic regression analysis to screen for factors associated with PI. RESULTS: There were 46 patients with PI. Result of univariate analysis suggested depth of stromal invasion, lymphovascular space invasion (LVSI), and lymph node metastasis, and uterine involvement was associated with PI (P < 0.05 for all). The multivariate analysis model included factors that could be diagnosed by a cone biopsy, and the result suggested nonsquamous histological type and LVSI was the independent factor of PI. The incidence of PI in the patients with no LVSI and squamous cancer was 6.97%. When the patients with inner 1/3 stromal invasion were stratified into those with squamous cancer and no LVSI, the incidence of PI was 1.17%. The incidence of PI in the patients with LVSI and nonsquamous cancer was 33.33%. CONCLUSIONS: The patients with inner 1/3 stromal invasion, no LVSI, and squamous histological type may be considered for less radical surgery. The patients with nonsquamous histological type and LVSI may be considered for radical hysterectomy including a complete resection of parametrium. PMID- 26905337 TI - Determination of charge carrier concentration in doped nonpolar liquids by impedance spectroscopy in the presence of charge adsorption. AB - The impedance of dodecane doped with sorbitan trioleate (Span 85), sorbitan monooleate (Span 80) and sorbitan monolaurate (Span 20) was measured as a function of frequency using a 10 mV amplitude sinusoidal voltage applied across a parallel plate cell with a 10 MUm spacing. The tested solutions varied in concentration from 1 mM to 100 mM and the frequency range was 10(-2)-10(4) Hz. Nyquist plots of all three surfactants showed the high frequency semicircle characteristic of parallel resistance and capacitance but often exhibited a second semicircle at low frequencies which was attributed to charge adsorption and desorption. The electrical conductivity of each surfactant was proportional to surfactant concentration for concentrations above 10mM. Fitting the data to models for charge migration, differential capacitance, and adsorption allowed extraction of both charge concentration and two kinetic parameters that characterize the rate of adsorption and desorption. Above 10 mM the ratio of charge carriers per surfactant molecule was 22 ppm for Span 20, 3 ppm for Span 80, and 0.2 ppm for Span 85. A higher number of charge carriers per molecule of surfactant was associated with larger micelles. The adsorption rate constants were independent of surfactant concentration while the desorption rate constants were proportional to the surfactant concentration. This dependence indicated that uncharged surfactant, whether in micelles or not, participated in the desorption of charge. Predictions of the adsorption/desorption model for large constant electric fields agreed qualitatively with data from the literature (Karvar et al., 2014). PMID- 26905338 TI - Characteristics of Antimicrobial Stewardship Programs at Veterans Affairs Hospitals: Results of a Nationwide Survey. AB - BACKGROUND Antimicrobial stewardship programs (ASPs) are variably implemented. OBJECTIVE To characterize variations of antimicrobial stewardship structure and practices across all inpatient Veterans Affairs facilities in 2012 and correlate key characteristics with antimicrobial usage. DESIGN A web-based survey regarding stewardship activities was administered to each facility's designated contact. Bivariate associations between facility characteristics and inpatient antimicrobial use during 2012 were determined. SETTING Total of 130 Veterans Affairs facilities with inpatient services. RESULTS Of 130 responding facilities, 29 (22%) had a formal policy establishing an ASP, and 12 (9%) had an approved ASP business plan. Antimicrobial stewardship teams were present in 49 facilities (38%); 34 teams included a clinical pharmacist with formal infectious diseases (ID) training. Stewardship activities varied across facilities, including development of yearly antibiograms (122 [94%]), formulary restrictions (120 [92%]), stop orders for antimicrobial duration (98 [75%]), and written clinical pathways for specific conditions (96 [74%]). Decreased antimicrobial usage was associated with having at least 1 full-time ID physician (P=.03), an ID fellowship program (P=.003), and a clinical pharmacist with formal ID training (P=.006) as well as frequency of systematic patient-level reviews of antimicrobial use (P=.01) and having a policy to address antimicrobial use in the context of Clostridium difficile infection (P=.01). Stop orders for antimicrobial duration were associated with increased use (P=.03). CONCLUSIONS ASP-related activities varied considerably. Decreased antibiotic use appeared related to ID presence and certain select practices. Further statistical assessments may help optimize antimicrobial practices. Infect Control Hosp Epidemiol 2016;37:647-654. PMID- 26905340 TI - Genetic Epidemiology and Public Health: The Evolution From Theory to Technology. AB - Genetic epidemiology represents a hybrid of epidemiologic designs and statistical models that explicitly consider both genetic and environmental risk factors for disease. It is a relatively new field in public health; the term was first coined only 35 years ago. In this short time, the field has been through a major evolution, changing from a field driven by theory, without the technology for genetic measurement or computational capacity to apply much of the designs and methods developed, to a field driven by rapidly expanding technology in genomic measurement and computational analyses while epidemiologic theory struggles to keep up. In this commentary, we describe 4 different eras of genetic epidemiology, spanning this evolution from theory to technology, what we have learned, what we have added to the broader field of public health, and what remains to be done. PMID- 26905339 TI - Job Strain and the Cortisol Diurnal Cycle in MESA: Accounting for Between- and Within-Day Variability. AB - Evidence of the link between job strain and cortisol levels has been inconsistent. This could be due to failure to account for cortisol variability leading to underestimated standard errors. Our objective was to model the relationship between job strain and the whole cortisol curve, accounting for sources of cortisol variability. Our functional mixed-model approach incorporated all available data-18 samples over 3 days-and uncertainty in estimated relationships. We used employed participants from the Multi-Ethnic Study of Atherosclerosis Stress I Study and data collected between 2002 and 2006. We used propensity score matching on an extensive set of variables to control for sources of confounding. We found that job strain was associated with lower salivary cortisol levels and lower total area under the curve. We found no relationship between job strain and the cortisol awakening response. Our findings differed from those of several previous studies. It is plausible that our results were unique to middle- to older-aged racially, ethnically, and occupationally diverse adults and were therefore not inconsistent with previous research among younger, mostly white samples. However, it is also plausible that previous findings were influenced by residual confounding and failure to propagate uncertainty (i.e., account for the multiple sources of variability) in estimating cortisol features. PMID- 26905341 TI - Domperidone for Treatment of Low Milk Supply in Breast Pump-Dependent Mothers of Hospitalized Premature Infants: A Clinical Protocol. AB - Mothers of hospitalized premature infants who choose to provide breast milk are at increased risk of an inadequate breast milk supply. When nonpharmacologic interventions to increase milk supply fail, clinicians are faced with limited options. There is no current evidence to support the use of herbal galactogogues in this population and a black box warning for metoclopramide for potential serious side effects. Thus, domperidone was the only known, effective option for treatment of low milk supply in this population. With a thorough review of the literature on domperidone and coordination with the obstetrical, neonatal, lactation, and pharmacology teams, a domperidone treatment protocol for mothers of hospitalized premature infants with insufficient milk supply was developed at our institution and is presented in this article. A comprehensive understanding of domperidone for use as a galactogogue with a standard treatment protocol will facilitate safer prescribing practices and minimize potential adverse reactions in mothers and their hospitalized premature infants. PMID- 26905342 TI - Expanding the Supply of Pasteurized Donor Milk: Understanding Why Peer-to-Peer Milk Sharers in the United States Do Not Donate to Milk Banks. AB - BACKGROUND: Lactating women in the United States have several options for what they do with excess breast milk, including donating to milk banks that serve medically fragile infants, sharing directly with families seeking milk, and selling to individuals or for-profit entities. The World Health Organization and the US Surgeon General have issued calls to increase access to pasteurized donor milk for medically fragile infants. OBJECTIVE: To explore how lactating women with a surplus of breast milk come to the decision to share their milk with a peer rather than donate to a milk bank. METHODS: A qualitative design using a grounded theory approach was employed. Semistructured telephone interviews were conducted with 27 women who had shared milk with a peer but not with a milk bank. RESULTS: Five dominant themes were identified: a strong belief in the value of breast milk, unexpected versus planned donation, sources of information regarding milk exchange, concerns and knowledge gaps about milk banks, and helping and connecting. CONCLUSIONS: This research offers insights into potential strategies for promoting milk bank donation among peer-to-peer milk sharers, including developing donor education campaigns focused on knowledge gaps regarding milk banks and developing health care professional referral programs that can reduce barriers associated with the convenience of milk bank donation. PMID- 26905343 TI - Nigella sativa and its active constituent thymoquinone in oral health. AB - In this review, we summarized published reports that investigated the role of Nigella sativa (NS) and its active constituent, thymoquinone (TQ) in oral health and disease management. The literature studies were preliminary and scanty, but the results revealed that black seed plants have a potential therapeutic effect for oral and dental diseases. Such results are encouraging for the incorporation of these plants in dental therapeutics and hygiene products. However, further detailed preclinical and clinical studies at the cellular and molecular levels are required to investigate the mechanisms of action of NS and its constituents, particularly TQ. PMID- 26905344 TI - Portfolios in Saudi medical colleges. Why and how? AB - Over recent decades, the use of portfolios in medical education has evolved, and is being applied in undergraduate and postgraduate programs worldwide. Portfolios, as a learning process and method of documenting and assessing learning, is supported as a valuable tool by adult learning theories that stress the need for learners to be self-directed and to engage in experiential learning. Thoughtfully implemented, a portfolio provides learning experiences unequaled by any single learning tool. The credibility (validity) and dependability (reliability) of assessment through portfolios have been questioned owing to its subjective nature; however, methods to safeguard these features have been described in the literature. This paper discusses some of this literature, with particular attention to the role of portfolios in relation to self-reflective learning, provides an overview of current use of portfolios in undergraduate medical education in Saudi Arabia, and proposes research-based guidelines for its implementation and other similar contexts. PMID- 26905345 TI - Epidemiology of oral cancer in Arab countries. AB - OBJECTIVES: To review the oral cancer (OC) studies that were conducted in Arab countries with regard to epidemiology, risk factors, and prognosis. METHODS: A computer-based PubMed literature search was performed to retrieve studies conducted in the Arab world on epidemiology of OC. After screening for exclusion criteria, cross-referencing, and searching local journals, a total of 19 articles were included. RESULTS: Eight prevalence studies found an OC prevalence ranging from 1.8 to 2.13 per 100,000 persons. Oral cancer patients were mostly in their fifth to sixth decade of life, and the incidence in younger age was reported in some Arab countries. Yemenis have an alarming high prevalence of OC among people younger than 45 years. Eleven studies explored determinants or prognosis of OC. Behavioral determinants such as smokeless tobacco (Shamma and Qat), and cigarette smoking were strongly associated with OC. Alcohol drinking and solar radiation exposures were cited as possible risk factors. The most affected sites were tongue, floor of the mouth, and lower lip variations in the affected site were attributed to the socio-cultural behavior of the populations under study. Squamous cell carcinoma was the most frequently detected cancer, and usually patients were in late stages (III and IV) at the time of diagnosis. CONCLUSION: No solid evidence exists regarding the true OC prevalence/incidence in most Arab countries due to the lack of national cancer registries and population-based studies. PMID- 26905346 TI - Detection of human papillomavirus infection by molecular tests and its relation to colonic polyps and colorectal cancer. AB - OBJECTIVES: To prospectively examine the association between human papilloma virus (HPV) colonization of the colonic mucosa and the development of colorectal polyps (CRPs), and colorectal cancer (CRC) in Saudi Arabia. METHODS: A case control study was performed between January 2013 and December 2014. All eligible patients underwent standard diagnostic colonoscopy. Patients with polyps or colorectal cancer were considered cases, while those with any other endoscopic findings were controls. Biopsy samples from polyps and tumors, and/or from normal colonic mucosa were acquired. Human papilloma virus colonization was detected using a hybrid capture technique of samples taken from both normal tissue, and CRPs and CRC. The association between HPV and CRPs/CRC was evaluated. RESULTS: A total of 132 patients were recruited. The mean age was 53 (+/- 15.9) years. Sixty patients had endoscopically detectable CRPs/CRC, and 72 had either inflammation or normal endoscopic evaluations. Only 4 (0.8%) of the 132 samples that were collected and analyzed were positive for the HPV gene. Statistical analysis did not identify any significant association between HPV colonization and the presence of CRPs/CRC. The only significant predictor of detecting CRPs/CRC on colonoscopy was symptomatic presentation (odds ratio=11.072, 95% confidence interval 4.7-26.2, p less than 0.001). CONCLUSION: Human papilloma virus colonic colonization is rare in Saudi Arabia. An association between HPV colonization and CRP/CRC development could not be identified in this cohort of patients. PMID- 26905347 TI - Comparison of different methods for measurement of electrolytes in patients admitted to the intensive care unit. AB - OBJECTIVES: To investigate whether electrolyte levels measured by using blood gas analyzers (ABG) and auto-analyzers (AA) are equivalent and can be used interchangeably. METHODS: This observational prospective study was conducted in 100 patients admitted to the Intensive Care Unit, Adnan Menderes University School of Medicine, Aydin, Turkey, between March and August 2014. Samples for both AA and ABG analyzers were collected simultaneously from invasive arterial catheters of patients. The electrolyte levels were measured by using 2 methods. RESULTS: The mean sodium level measured by ABG was 136.1 +/- 6.3 mmol/L and 137.8 +/- 5.4 mmol/L for AA (p=0.001). The Pearson's correlation coefficient was 0.561 (p less than 0.001). The Bland-Altman 95% limits of agreement were -9.4 to 12.6 mmol/L. The mean potassium levels measured by ABG was 3.4 +/- 0.7 mmol/L and AA was 3.8 +/- 0.7 mmol/L (p=0.001). The Bland-Altman comparison limits were -0.58 to 1.24 and the associated Pearson's correlation coefficient was 0.812 (p less than 0.001). CONCLUSION: The results of the 2 analyzing methods, in terms of sodium, were not equivalent and could not be used interchangeably. However, according to the statistical analyses results, by including, but not blindly trusting these findings, urgent and vital decisions could be made by the potassium levels obtained from the BGA, but a simultaneous follow-up sample had to be sent to the central laboratory for confirmation. PMID- 26905348 TI - Diagnostic efficacy of random albumin creatinine ratio for detection of micro and macro-albuminuria in type 2 diabetes mellitus. AB - OBJECTIVES: To compare a less cumbersome random albumin creatinine ratio (RACR) with 24-hour urinary albumin excretion (UAE) for detection of renal damage in patients with type 2 diabetes mellitus (T2DM). METHODS: This retrospective study performed between March 2013 and June 2014 at the Department of Pathology, King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia included 122 patients (mean age 54 +/- 15, 104 females and 18 males) with T2DM. Urine albumin levels of less than 30 mg/g was considered normal, from 30-300 mg/g considered as micro albuminuria, and over 300 mg/g considered as macro-albuminuria. RESULTS: Concordance between the 2 assays was observed in 114 (93.4%) samples. The sensitivity of RACR assay was 100%, specificity was 91.3% with a positive predictive value (PPV) of 95%, and a negative predictive value (NPV) of 100% in micro-albuminuria range. For macro-albuminuria, RACR had a sensitivity of 100%, specificity of 94.1% with PPV of 94% and NPV of 100%. Receiver operating characteristic (ROC) curves analysis cut-off values of 40 mg/g-300 mg/g for micro and greater than 300 mg/g for macro-albuminuria revealed 100% sensitivity, 97.5% specificity, 95% PPV, and 100% NPV for micro-albuminuria, and 100% sensitivity, 94% specificity, 76% PPV, and 100% NPP for macro-albuminuria. The area under the curve for micro-albuminuria was 100% and 98.2% for macro-albuminuria. CONCLUSION: Performance of RACR was comparable to 24 hour UAE assay particularly in excluding renal damage in T2DM. PMID- 26905349 TI - Occurrence and antibacterial susceptibility pattern of bacterial pathogens isolated from diarrheal patients in Pakistan. AB - OBJECTIVE: To determine the occurrence of bacterial pathogens responsible for diarrhea and to engender information regarding the effectiveness of commonly used antibiotic against diarrhea. METHODS: This cross-sectional study was conducted between April and July 2014. Samples were collected from the Divisional Headquarter and Allied Hospital, Faisalabad, Pakistan. The differential and selective media were used to isolate bacterial pathogens, which were identified through cultural characteristics, microscopy, and biochemical tests. Disc diffusion assay was carried out using Muller Hinton agar medium, and minimum inhibitory concentration was determined using broth dilution method against isolated pathogens. RESULTS: One hundred and forty-one (100%) samples were positive for some bacteria. Frequency of occurrence was Bacillus cereus (B. cereus) (66%), Escherichia coli (E.coli) (48.5%), Salmonella typhi (S. Typhi) (27.7%), Pseudomonas aeruginosa (P. aeruginosa) (8.5%), and Staphylococcus aureus (S. aureus) (4.3%). Single pathogen was detected in 20 (14.2%) samples whereas combinations were found in 121 (85.8%) samples. Bacillus cereus and E.coli were the most frequently detected pathogens followed by the S. Typhi, P. aeruginosa, and Staph. aureus. The percentage occurrence of isolated pathogens was 31% in B. cereus, 31% in E. coli, 18% in S. Typhi, 5% in P. aeruginosa, and 3% in Staph. aureus. CONCLUSION: Pseudomonas aeruginosa showed resistance against Amoxicillin and Cefotaxime, whereas S. aureus was found resistant against Cefotaxime. Statistical analysis using one way Analysis of Variance revealed that Ofloxacin and Gentamicin had significant (p less than 0.05) differences against all isolates as compared with other antibiotics used in this study. PMID- 26905350 TI - Prevalence and risk factors of early fecal carriage of Enterococcus faecalis and Staphylococcus spp and their antimicrobial resistant patterns among healthy neonates born in a hospital setting in central Saudi Arabia. AB - OBJECTIVES: To investigate the prevalence, antibiotic resistant profiles, and risk factors of early fecal carriage of Enterococcus faecalis (E. faecalis) and staphylococci among 150 healthy Saudi neonates born in a hospital setting in central Saudi Arabia. METHODS: This prospective study was conducted in Al Bukayriyah General Hospital, Qassim, Saudi Arabia, between June 2012 and January 2013. The E. faecalis and Staphylococcus spp. isolates were identified manually, and Vitek2 system was used for identity confirmation at the species level and minimum inhibitory concentration-susceptibility testing. RESULTS: Enterococcus faecalis (n=73) and Staphylococcus spp. (n=18) were recovered. Unlike staphylococci, E. faecalis colonization did not significantly vary from day one up to 7 days of life, regardless of the type of feeding, but it was relatively higher among vaginally versus cesarean delivery. Both Staphylococcus epidermidis (S. epidermidis) and Staphylococcus aureus (S. aureus) carriage increase as the body weight increases, and this difference was significant (p=0.025) for S. epidermidis. High-level resistance in Gentamycin among E. faecalis isolates was 25% and 11% to Streptomycin. Thirty percent of S. epidermidis were resistant to oxacillin and exhibited multidrug-resistant (MDR) patterns of 5 resistant markers, which were also observed among 2/5 (40%) of Methicillin-resistant Staphylococcus aureus isolates. CONCLUSION: Enterococcus faecalis did not significantly vary in relation to type of delivery, age up to 7 days, and type of feeding. The neonatal fecal carriage of MDR isolates should be considered as a crucial reservoir to the further spread of antimicrobial resistance genes among hospitals, cross infections, and the community. PMID- 26905351 TI - Effects of acetic acid on the viability of Ascaris lumbricoides eggs. Is vinegar reliable enough to clean the vegetables? AB - OBJECTIVES: To investigate the effects of acetic acid on durable Ascaris lumbricoides (A. lumbricoides) eggs to determine the effective concentration of vinegar and the implementation period to render the consumption of raw vegetables more reliable. METHODS: This experimental study was performed in May 2015 in the Parasitology Laboratory, Faculty of Medicine, Yuzuncu Yil University, Van, Turkey. The A. lumbricoides eggs were divided into 2 groups. Eggs in the study group were treated with 1, 3, 5, and 10% acetic acid concentrations, and eggs in the control group were treated with Eosin. The eggs' viability was observed at the following points in time during the experiment: 0, 10, 15, 20, 30, 45, and 60 minutes. RESULTS: The 1% acetic acid was determined insufficient on the viability of Ascaris eggs. At the 30th minute, 3% acetic acid demonstrated 95% effectiveness, and at 5% concentration, all eggs lost their viability. Treatment of acetic acid at the ratio of 4.8% in 30 minutes, or a ratio of 4.3% in 60 minutes is required for full success of tretment. CONCLUSION: Since Ascaris eggs have 3 layers and are very resistant, the acetic acid concentration, which can be effective on these eggs are thought to be effective also on many other parasitic agents. In order to attain an active protection, after washing the vegetables, direct treatment with a vinegar containing 5% acetic acid for 30 minutes is essential. PMID- 26905352 TI - Growth assessment and risk factors of malnutrition in children with cystic fibrosis. AB - OBJECTIVES: To evaluate the nutritional status, to screen for the presence of malnutrition, and to study the possible risk factors associated with malnutrition in patients with cystic fibrosis (CF). METHODS: A retrospective cross-sectional review of medical records of all diagnosed CF patients in the Pediatric Department, Salmaniya Medical Complex, Manama, Kingdom of Bahrain, between January 1984 and May 2015 was conducted. Demographic and anthropometric data were collected from records of last visit to CF clinic. Nutritional status and risk factors of malnutrition were assessed. RESULTS: All records of 109 CF patients were reviewed. Forty-seven pediatric patients were included in the study. All included patients were on pancreatic enzyme replacement and 42 (89%) received high-calorie supplementation. Growth failure was noted in 34 (72%) patients, 19 (56%) were wasted and stunted, 8 (23.5%) were wasted only, and 7 (20.5%) were stunted. Low birth weight (p=0.032), and the presence of gastroesophageal reflux disease (GERD) (p=0.039) were the significant risk factors for malnutrition. CONCLUSIONS: Most CF patients in Bahrain (72%) are malnourished. Low birth weight and the presence of GERD are risk factors. PMID- 26905353 TI - Electrophysiologic pattern and prevalence of subclinical peripheral neuropathy in children and adolescents with type I diabetes mellitus in Iran. AB - OBJECTIVES: To evaluate electrophysiologic pattern of subclinical diabetic peripheral neuropathy (DPN) in children and adolescents with type 1 diabetes mellitus (T1DM) based on nerve conduction study. METHODS: In this cross sectional study, 40 children and adolescents (62.5% female with mean age of 12.73 +/- 0.43 years) with T1DM for at least 5 years attending the Pediatrics Clinics. Tabriz University of Medical Sciences, Tabriz, Iran, between 2014 and 2015 were recruited. Demographic and laboratory findings were recorded and all patients underwent clinical neurological examination and electrophysiologic studies. RESULTS: According to electrophysiologic studies, DPN was found in 57.5% of patients including early stage of neuropathy (15%), mild sensory axonal neuropathy (25%), mild sensory motor axonal neuropathy (10%), and moderate sensory motor axonal neuropathy (7.5%). Age, duration of diabetes, fasting blood sugar, and glycosylated hemoglobin levels had no significant difference between patients with and without DPN. Reduced deep tendon reflexes were observed in the upper limb (30%) and lower limb (47.5%) of patients, which were both significantly higher in DPN patients (upper limb [p=0.03] and lower limb [p=0.04]). The most frequent electrophysiologic findings were unobtainable H reflex, low amplitude sural, and median sensory responses. CONCLUSION: Subclinical DPN is a common complication found in children and adolescents with TIDM and peripheral sensory axonal neuropathy is the most frequent type. Nerve conduction study is recommended for early detection of DPN and prevention of its progress. PMID- 26905354 TI - The effect of air-lock technique on pain at the site of intramuscular injection. AB - OBJECTIVES: To investigate the effects of air-lock technique (ALT) on pain of intramuscular (IM) injection delivered to the ventrogluteal and dorsogluteal site (DS). METHODS: A randomized controlled trial design was used to assess the pain intensity associated with IM injections administered using 2 different methods and injection sites. Recruitment of patients was carried out between April and August 2013 at the Department of Brain Surgery, Cekirge State Hospital, Bursa, Turkey. The sample comprised 60 patients who developed no complications at the IM site, and had no illness that could affect their perception of pain. The patients were randomly divided into 2 groups of 30 patients. Patients in the first group received injections in the ventrogluteal site (VS), while the DS was used for injections in the second group. Patients in each group received 2 injections, one using ALT and one not using the technique. After each injection, the pain felt by patients during the injection was immediately assessed using a visual analog scale. RESULTS: The mean pain score after injections to the DS by the ALT was 3.30 +/- 2.70, while the mean pain score after injections to the VS using the same technique was 2.53 +/- 2.52. CONCLUSION: Although the difference between groups was not significant, the results of the study supported the idea that injections delivered to the VS by ALT are less painful than those delivered to the DS. PMID- 26905355 TI - Comparison of clinical and sociodemographic features of bipolar disorder patients with those of social anxiety disorder patients comorbid with bipolar disorder in Turkey. AB - OBJECTIVES: To assess the impact of social anxiety disorder (SAD) comorbidity on the clinical features, illness severity, and response to mood stabilizers in bipolar disorder (BD) patients. METHODS: This retrospective study included bipolar patients that were treated at the Department of Psychiatry, Haseki Training and Research Hospital, Istanbul, Turkey in 2015, and who provided their informed consents for participation in this study. The study was conducted by assessing patient files retrospectively. Two hundred bipolar patients were assessed using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th Edition axis-I (SCID-I) in order to detect all possible comorbid psychiatric diagnoses. The sample was split according to the presence of SAD comorbidity and the groups were compared. RESULTS: The SAD comorbidity was detected in 17.5% (35/200) of the BD patients. The SAD comorbid bipolar patients were more educated, had earlier onset of BD, lower number of manic episodes, and more severe episodes. There was no difference between groups in terms of total number of episodes, hospitalization, suicidality, being psychotic, treatment response to lithium and anticonvulsants. CONCLUSION: Social anxiety disorder comorbidity may be associated with more severe episodes and early onset of BD. However, SAD comorbidity may not be related to treatment response in bipolar patients. PMID- 26905356 TI - Kimura disease: No age or ethnicity limit. AB - Kimura disease is a chronic inflammatory disease that mainly manifests as a lump in the cervical region. Although the underlying pathophysiology is not clear yet, the diagnosis can be established based on specific histopathological characteristics. The first case of this disease was described in China, as well as the majority of subsequent cases that were also described in the Far East countries made Kimura disease traditionally a disease of adult patients of Asian descent. This report describes the occurrence of Kimura disease in pediatric non Asian patient with a similar clinicopathologic presentation. PMID- 26905357 TI - Laparoscopic repair of diaphragm perforation with heart patch after microwave ablation. AB - Microwave ablation (MWA) is a new technology developed in recent years, which is widely used in various disciplines. Microwave ablation is an alternative to surgery in the management of various tumors, and it has been demonstrated to be effective in the management of primary tumors and metastatic tumors. Microwave ablation is widely used in the treatment of hepatocellular carcinoma with an obvious effect and less side effects, and only 2.7% had serious complications. Many studies have confirmed the complications are thermal damage, hemorrhage, pleural effusion, bile leak, tumor seeding, hepatic abscess, cholangitis, and so forth. But diaphragm perforation is rare, and it is probably the first case reported. This article describes diaphragmatic perforation secondary to MWA of the liver with subsequent pleural effusion and diaphragmatic hernia. We also describe its management via the laparoscopic approach. PMID- 26905358 TI - Imaging of non-traumatic acute abdominal pain in adults presenting to the emergency department. PMID- 26905359 TI - Overcoming language barrier in healthcare settings using information and communication technologies. PMID- 26905360 TI - Frequency, incidence, and prevalence. PMID- 26905361 TI - Effect of Statins on Kidney Disease Outcomes: A Systematic Review and Meta analysis. AB - BACKGROUND: The effects of statin administration on kidney disease outcomes remain controversial. We undertook a systematic review and meta-analysis to assess the efficacy of statins on kidney outcomes. STUDY DESIGN: We conducted a meta-analysis of randomized controlled trials (RCTs) using MEDLINE (1946 to August 31, 2015), EMBASE (1966 to August 31, 2015), and the Cochrane Library database (no date restriction). SETTING & POPULATION: Adults who were not receiving dialysis, for whom kidney disease outcomes were reported. SELECTION CRITERIA FOR STUDIES: RCTs in which statins were given for at least 6 months and kidney outcomes were measured. INTERVENTION: Statins versus control, including placebo, usual care, and different types or doses of statins. OUTCOMES: Kidney failure events, rate of change in estimated glomerular filtration rate (eGFR) per year, change in proteinuria or albuminuria, and, in patients with chronic kidney disease, major cardiovascular events. RESULTS: 57 eligible studies with 143,888 participants were included. Statin treatment did not produce an apparent beneficial effect for kidney failure events (OR, 0.98; 95% CI, 0.87-1.10; P=0.7) or end-stage renal disease events (OR, 0.98; 95% CI, 0.90-1.07; P=0.7). However, mean difference for rate of decline in eGFR (0.41 [95% CI, 0.11-0.70] mL/min/1.73m(2) per year slower in statin recipients) and standardized mean difference for change in proteinuria or albuminuria (-0.65 [95% CI, -0.94 to 0.37] standard deviation units, statin recipients vs controls) were statistically significant. In addition, statin therapy significantly reduced the risk for cardiovascular events (OR, 0.69; 95% CI, 0.61-0.79; P<0.001) in patients with chronic kidney disease. LIMITATIONS: Inclusion of several post hoc analyses from large RCTs and substantial heterogeneity in secondary outcome analyses. CONCLUSIONS: Statin therapy does not reduce the risk for kidney failure events in adults not receiving dialysis for whom kidney disease outcomes were reported, but may modestly reduce proteinuria and rate of eGFR decline. PMID- 26905362 TI - Exhaled Nitric Oxide Levels Among Adults With Excessive Alcohol Consumption. AB - BACKGROUND: More than one-quarter of the US population qualify as excessive alcohol consumers. Alcohol use impacts several lung diseases, and heavy consumption has been associated with poor clinical outcomes. The fractional excretion of exhaled nitric oxide (Feno) has clinical implications in multiple airways diseases. We hypothesized that excessive alcohol intake is associated with lower Feno levels. METHODS: To test this hypothesis, we examined a sample consisting of 12,059 participants, aged 21 to 79 years, interviewed between 2007 and 2012 from the National Health and Examination Survey. Two valid Feno measurements that were reproducible were recorded. Alcohol questionnaire data were used to define the following alcohol groups: never drinkers, nonexcessive drinkers, excessive drinkers, and former excessive drinkers. The natural logarithm of Feno values [ln(Feno)] as well as blood eosinophil count and C reactive protein were used as dependent variables to test the association with alcohol groups including multivariable linear regression models with adjustment for predictors of Feno. RESULTS: Excessive alcohol consumption comprised 3,693 (26.9%) of the US sample population. Controlling for all other factors, excessive alcohol consumption had a negative association and was an independent predictor for ln(Feno) levels in comparison with the never-drinker group (-0.11; 95% CI, 0.17 to -0.06; P < .001). ln(Feno) levels decreased across categories of increasing alcohol use (P < .001). CONCLUSIONS: Accounting for alcohol use in the interpretation of Feno levels should be an additional consideration, and further investigations are warranted to explore the complex interaction between alcohol and nitric oxide in the airways. PMID- 26905364 TI - Analysis of National Trends in Admissions for Pulmonary Embolism. AB - BACKGROUND: Pulmonary embolism (PE) remains a significant cause of hospital admission and health-care costs. Estimates of PE incidence came from the 1990s, and data are limited to describe trends in hospital admissions for PE over the past decade. METHODS: We analyzed Nationwide Inpatient Sample data from 1993 to 2012 to identify patients admitted with PE. We included admissions with International Classification of Diseases, 9th revision, codes listing PE as the principal diagnosis as well as admissions with PE listed secondary to principal diagnoses of respiratory failure or DVT. Massive PE was defined by mechanical ventilation, vasopressors, or nonseptic shock. Outcomes included hospital lengths of stay, adjusted charges, and all-cause hospital mortality. Linear regression was used to analyze changes over time. RESULTS: Admissions for PE increased from 23 per 100,000 in 1993 to 65 per 100,000 in 2012 (P < .001). The percent of admissions meeting criteria for massive PE decreased (5.3% to 4.4%, P = .002), but the absolute number of admissions for massive PE increased (from 1.5 to 2.8 per 100,000, P < .001). Median length of stay decreased from 8 (interquartile range [IQR], 6-11) to 4 (IQR, 3-6) days (P < .001). Adjusted hospital charges increased from $16,475 (IQR, $10,748-$26,211) in 1993 to $25,728 (IQR, $15,505 $44,493) in 2012 (P < .001). All-cause hospital mortality decreased from 7.1% to 3.2% (P < .001), but population-adjusted deaths during admission for PE increased from 1.6 to 2.1 per 100,000 (P < .001). CONCLUSIONS: Total admissions and hospital charges for PE have increased over the past two decades. However, the population-adjusted admission rate has increased disproportionately to the incidence of patients with severe PE. We hypothesize that these findings reflect a concerning national movement toward more admissions of less severe PE. PMID- 26905363 TI - Gun Violence, African Ancestry, and Asthma: A Case-Control Study in Puerto Rican Children. AB - BACKGROUND: Exposure to gun violence and African ancestry have been separately associated with increased risk of asthma in Puerto Rican children. OBJECTIVE: The objective of this study was to examine whether African ancestry and gun violence interact on asthma and total IgE in school-aged Puerto Rican children. METHODS: This is a case-control study of 747 Puerto Rican children aged 9 to 14 years living in San Juan, Puerto Rico (n = 472), and Hartford, Connecticut (n = 275). Exposure to gun violence was defined as the child's report of hearing gunshots more than once, and the percentage of African ancestry was estimated using genome wide genotypic data. Asthma was defined as parental report of physician-diagnosed asthma and wheeze in the previous year. Serum total IgE (IU/mL) was measured in study participants. Multivariate logistic and linear regressions were used for the analysis of asthma and total IgE, respectively. RESULTS: In multivariate analyses, there was a significant interaction between exposure to gun violence and African ancestry on asthma (P = .001) and serum total IgE (P = .04). Among children exposed to gun violence, each quartile increase in the percentage of African ancestry was associated with approximately 45% higher odds of asthma (95% CI, 1.15-1.84; P = .002) and an approximately 19% increment in total IgE (95% , 0.60-40.65, P = .04). In contrast, there was no significant association between African ancestry and asthma or total IgE in children not exposed to gun violence. CONCLUSIONS: Our results suggest that exposure to gun violence modifies the estimated effect of African ancestry on asthma and atopy in Puerto Rican children. PMID- 26905365 TI - CT Imaging Assessment of Response to Treatment in Chronic Pulmonary Aspergillosis. AB - BACKGROUND: Long-term antifungal therapy is usually the only treatment option for chronic pulmonary aspergillosis. However, response rates are difficult to compare because the reported clinical, mycologic, or radiologic criteria are not standardized. Objective parameters are therefore needed. To define the most relevant CT imaging variables in assessment of response to treatment, we investigated changes over time in CT imaging variables. METHODS: Changes in CT imaging variables were assessed by systematic analysis of the CT scan findings of 36 patients at diagnosis and 6 months after initiation of treatment. The relevant radiologic variables were determined by selecting those showing significant changes over time. Two experienced thoracic radiologists, blinded for clinical and serologic response, independently performed CT scan analyses. Interreader agreement and concordance between radiologic and clinical response were evaluated. RESULTS: Of the 36 patients, seven experienced clinical deterioration while undergoing therapy. Significantly evolving radiologic variables included cavity and pleural wall thickening (P < .05), which were associated with clinical improvement. There was a strong association between fungus ball disappearance and cavity/pleural wall thickening reduction and clinical improvement (P = .04). There was poor agreement between size changes of cavities or nodules, and clinical evolution (Cohen's kappa, -0.13 to -0.24). CONCLUSIONS: Variations in cavity and pleural wall thickness may be the most relevant CT imaging variables for assessing response to treatment. Loss of fungus ball is strongly associated with clinical and radiologic improvement, but cavity size changes are unrelated to chronic pulmonary aspergillosis evolution. All these CT imaging variables may be applied in future clinical trials to assess treatment outcome. PMID- 26905366 TI - A Novel PF4-Dependent Platelet Activation Assay Identifies Patients Likely to Have Heparin-Induced Thrombocytopenia/Thrombosis. AB - BACKGROUND: Almost without exception, patients with heparin-induced thrombocytopenia/thrombosis (HIT) have antibodies that recognize platelet factor 4 (PF4) in a complex with heparin; however, many heparin-treated patients without HIT are also antibody-positive. A platelet activation test, the serotonin release assay (SRA), is useful for identifying a subset of antibodies that are platelet activating and most likely to cause HIT. However, this "gold standard" assay for HIT diagnosis is technically demanding and is routinely available only through referral laboratories, limiting its availability for timely diagnosis and management. METHODS: We compared the diagnostic performance of the SRA with that of a technically simple platelet activation assay, the PF4-dependent P-selectin expression assay (PEA), which uses platelets pretreated with PF4 as targets for antibody detection. Archived serum samples from 91 patients for whom clinical information (HIT 4Ts [thrombocytopenia, timing of platelet count fall, thrombosis, and other causes of thrombocytopenia] score) was available were used. Patients with an intermediate 4Ts score and a PF4 ELISA (enzyme-linked immunosorbent assay) optical density >= 2.0, or a high 4Ts score and a PF4 ELISA optical density >= 1.0, were considered HIT positive; others were designated HIT negative. RESULTS: The PEA had higher diagnostic accuracy (area under the curve, 0.92 vs 0.82; P = .02) than the SRA, using this definition of HIT. Eleven of 16 serum samples that were PEA positive and SRA negative were HIT positive. Studies done with identical target platelets and serially diluted samples from patients with HIT showed that the PEA is inherently more sensitive than the SRA for the detection of platelet-activating antibodies. CONCLUSIONS: The PEA is technically less demanding than the SRA and may be more accurate for the diagnosis of HIT. PMID- 26905368 TI - Gold-nanoparticles ingestion disrupts reproduction and development in the German cockroach. AB - The present work shows the effects of gold nanoparticles (AuNPs) orally administered on reproduction and development of the insect Blattella germanica. Newly emerged females were provided with food containing AuNPs (87.44MUg/g) of a size between 15 and 30nm (mean 21.8nm), and were allowed to mate with males. Food ingestion, mortality, reproductive parameters (time to ootheca formation and eclosion, ootheca viability and fertility) as well as postembryonic developmental parameters of the first ootheca (nymphal survival and life span) were recorded throughout the experiment. Gold from AuNPs was accumulated by adults of B. germanica with a bioaccumulation factor of 0.1. Ingestion of AuNPs did not disturb the time for ootheca formation nor ootheca eclosion. However, ootheca viability was decreased almost by 25% in AuNPs treated females in comparison to controls. At the same time the number of hatched nymphs was decreased by 32.8% (p<0.001) in AuNP group respect to control one. The postembryonic developmental parameters were also affected by AuNPs treatment, with a 35.8% of decrease (p<0.01) in number of nymphs that moulted to second and third instars and a reduction of their life span. Ingestion of AuNPs causes sublethal effects in B. germanica that compromises life-traits involved in population dynamics. B. germanica is proposed as a model species in nanotoxicological studies for urban environments. PMID- 26905367 TI - Removal of pinned scroll waves in cardiac tissues by electric fields in a generic model of three-dimensional excitable media. AB - Spirals or scroll waves pinned to heterogeneities in cardiac tissues may cause lethal arrhythmias. To unpin these life-threatening spiral waves, methods of wave emission from heterogeneities (WEH) induced by low-voltage pulsed DC electric fields (PDCEFs) and circularly polarized electric fields (CPEFs) have been used in two-dimensional (2D) cardiac tissues. Nevertheless, the unpinning of scroll waves in three-dimensional (3D) cardiac systems is much more difficult than that of spiral waves in 2D cardiac systems, and there are few reports on the removal of pinned scroll waves in 3D cardiac tissues by electric fields. In this article, we investigate in detail the removal of pinned scroll waves in a generic model of 3D excitable media using PDCEF, AC electric field (ACEF) and CPEF, respectively. We find that spherical waves can be induced from the heterogeneities by these electric fields in initially quiescent excitable media. However, only CPEF can induce spherical waves with frequencies higher than that of the pinned scroll wave. Such higher-frequency spherical waves induced by CPEF can be used to drive the pinned scroll wave out of the cardiac systems. We hope this remarkable ability of CPEF can provide a better alternative to terminate arrhythmias caused by pinned scroll waves. PMID- 26905369 TI - Development of an oncolytic HSV vector fully retargeted specifically to cellular EpCAM for virus entry and cell-to-cell spread. AB - Oncolytic herpes simplex virus (HSV) vectors have attracted increasing attention as novel anti-cancer agents. HSV entry is triggered by the binding of glycoprotein D (gD) to its receptors, such as herpesvirus entry mediator or nectin-1. We have recently reported the construction of a fully retargeted HSV platform that incorporates single-chain antibodies (scFv) into gD to mediate entry exclusively via tumor-associated antigens. In this study, we created an scFv directed against epithelial cell adhesion molecule (EpCAM), a recognized carcinoma-associated antigen, and inserted it into the retargeted HSV platform that is ablated for gD recognition of its canonical receptors and contains the entry-enhancing mutations in gB we previously identified. We observed that both initial entry and subsequent cell-to-cell spread of the retargeted virus were stringently dependent on cellular EpCAM expression. Interestingly, the retargeted virus developed larger plaques on some of the human tumor lines tested than the control virus bearing wild-type gD. Intratumoral injection of the retargeted virus revealed antitumor activity in a mouse xenograft model. These observations illustrate the versatility of our retargeted HSV platform as it allows expansion of the oncolytic virus toolbox for the treatment of diverse cancers. PMID- 26905371 TI - Delta-9-tetrahydrocannabinol (THC) history fails to affect THC's ability to induce place preferences in rats. AB - RATIONALE: In pre-clinical models of marijuana abuse, there is relatively limited evidence of delta-9-tetrahydrocannabinol's (THC) rewarding effects, as indexed by its general inability to induce a place preference. One explanation for this failure is that its rewarding effects are masked by its concurrently occurring aversive properties. Consistent with this explanation, THC pre-exposure, which presumably weakens its aversive effects, induces place preferences. Such demonstrations are limited to mice and given reported species differences in THC reactivity, it is unknown to what extent the same shift in affective properties would be evident in rats. METHODS: The present experiment examined the effect of THC history (3.2mg/kg) on THC (1 or 3.2mg/kg) induced place preference conditioning in rats. An assessment of taste avoidance was also run to independently characterize THC's aversive effects and any changes that occurred with drug pre-exposure. These assessments were made in a combined taste avoidance/place preference procedure in which a novel saccharin solution and environment were paired with THC (0, 1 or 3.2mg/kg). RESULTS: THC did not induce place conditioning, and a history of THC was ineffective in increasing THC's ability to do so, despite the fact that this same history significantly attenuated the aversive effects of THC. CONCLUSIONS: The failure of THC to consistently induce place preferences has been argued to be a function of its concurrently occurring aversive effects masking its rewarding properties. The fact that pre-exposure to THC significantly reduced its aversive effects without impacting THC's ability to induce place preferences suggests that THC has weak rewarding effects and/or its residual aversive affects may have still masked its rewarding properties. An important area for future work will be characterizing under what conditions THC is rewarding and whether its overall reinforcing effects are impacted by the relationship between its affective properties. PMID- 26905370 TI - Intravesical treatment of advanced urothelial bladder cancers with oncolytic HSV 1 co-regulated by differentially expressed microRNAs. AB - Urothelial bladder cancer is the most common malignancy of the urinary tract. Although most cases are initially diagnosed as non-muscle-invasive, more than 80% of patients will develop recurrent or metastatic tumors. No effective therapy exists currently for late-stage metastatic tumors. By intravesical application, local administration of oncolytic Herpes Simplex virus (oHSV-1) can provide a promising new therapy for this disease. However, its inherent neurotoxicity has been a perceived limitation for such application. In this study, we present a novel microRNA-regulatory approach to reduce HSV-1-induced neurotoxicity by suppressing viral replication in neurons while maintaining oncolytic selectivity toward urothelial tumors. Specifically, we designed a recombinant virus that utilizes differentially expressed endogenous microR143 (non-cancerous, ubiquitous) and microR124 (neural-specific) to regulate expression of ICP-4, a gene essential for HSV-1 replication. We found that expression of ICP-4 must be controlled by a combination of both miR143 and miR124 to achieve the most effective attenuation in HSV-1-induced toxicity while retaining maximal oncolytic capacity. These results suggest that interaction between miR143 and miR124 may be required to successfully regulate HSV-1 replication. Our resent study is the first proof-in-principle that miRNA combination can be exploited to fine-tune the replication of HSV-1 to treat human cancers. PMID- 26905372 TI - Aortic Neck Anatomic Features and Predictors of Outcomes in Endovascular Repair of Abdominal Aortic Aneurysms Following vs Not Following Instructions for Use. AB - BACKGROUND: A significant number of patients undergo endovascular repair of abdominal aortic aneurysms (EVAR) outside the instructions for use (IFU). This study will examine various aortic neck features and their predictors of clinical outcomes. STUDY DESIGN: We performed a retrospective analysis of prospectively collected data on EVAR patients. Neck features outside IFU were analyzed. Kaplan Meier and multivariate analyses were used to predict their effect as single features, or in combination, on outcomes. RESULTS: Fifty-two percent of 526 patients had 1 or more features outside the IFU. The overall technical success rate was 99%, and perioperative complication rates were 7% and 12% for IFU vs outside IFU use, respectively (p = 0.04). Type I early endoleak and early intervention rates were 7% and 10% for IFU vs 18% and 24% for outside IFU (p = 0.0002 and p < 0.0001). At a mean follow-up of 30 months, freedom from late type I endoleak and late reintervention at 1, 2, and 3 years for IFU were 99.5%, 99.5%, and 98.4%, and 99.4%, 98%, and 96.8%; vs 98.9%, 98.1%, and 98.1%, and 97.5%, 96.2%, and 95.2% for outside IFU (p = 0.049 and 0.799), respectively. Survival rates at 1, 2, and 3 years for IFU were 97%, 93.5%, and 89.8%; vs 93.7%, 88.8%, and 86.3% for outside IFU (p = 0.035). Multivariate analysis showed that a neck angle > 60 degrees had odds ratios for death, sac expansion, and early intervention of 6, 2.6, and 3.3, respectively; neck length < 10 mm had odds ratios of 2.8 for deaths, 3.4 for early intervention, 4.6 for late reintervention, and 4.3 for late type I endoleak. CONCLUSIONS: Patients with neck features outside IFU can be treated with EVAR; however, they have higher rates of early and late type I endoleak, early intervention, and late death. PMID- 26905374 TI - Amino-Functionalized Metal-Organic Frameworks Nanoplates-Based Energy Transfer Probe for Highly Selective Fluorescence Detection of Free Chlorine. AB - Novel highly fluorescent NH2-MIL-53(Al) was controllably synthesized by a facile one-step hydrothermal treatment of AlCl3.6H2O and NH2-H2BDC in water with urea as a modulator. The as-synthesized NH2-MIL-53(Al) nanoplates exhibited excellent water solubility and stability. In the present work, it can be found that strong fluorescence of NH2-MIL-53(Al) nanoplates was significantly suppressed after the addition of free chlorine, and a simple sensing system for fast, highly selective direct detection of free chlorine in water was established. Compared with other fluorescent sensors for free chlorine, the present methodology has a comparable detection limit of 0.04 MUM (S/N = 3) and a wide detection range of 0.05 to 15 MUM. On the other hand, the traditional redox-based fluorescent probes sharply suffered from the interference of MnO4(-), Cr2O7(2-), and other oxidants with stronger oxidation capability than free chlorine while ours overcame this disadvantage. Further research suggests that it is more likely the energy transfer through N-H...O-Cl hydrogen bonding interaction between amino group and ClO(-) ions plays the key role in our system, providing a new and promising platform for free chlorine determination in water quality monitoring. PMID- 26905375 TI - Current Cell-Based Strategies for Whole Kidney Regeneration. AB - Chronic kidney diseases affect thousands of people worldwide. Although hemodialysis alleviates the situation by filtering the patient's blood, it does not replace other kidney functions such as hormone release or homeostasis regulation. Consequently, orthotopic transplantation of donor organs is the ultimate treatment for patients suffering from end-stage renal failure. Unfortunately, the number of patients on the waiting list far exceeds the number of donors. In addition, recipients must remain on immunosuppressive medications for the remainder of their lives, which increases the risk of morbidity due to their weakened immune system. Despite recent advancements in whole organ transplantation, 40% of recipients will face rejection of implanted organs with a life expectancy of only 10 years. Bioengineered patient-specific kidneys could be an inexhaustible source of healthy kidneys without the risk of immune rejection. The purpose of this article is to review the pros and cons of several bioengineering strategies used in recent years and their unresolved issues. These strategies include repopulation of natural scaffolds with a patient's cells, de novo generation of kidneys using patient-induced pluripotent stem cells combined with stepwise differentiation, and the creation of a patient's kidney in the embryos of other mammalian species. PMID- 26905373 TI - Over the counter (OTC) artificial tear drops for dry eye syndrome. AB - BACKGROUND: Over the counter (OTC) artificial tears historically have been the first line of treatment for dry eye syndrome and dry eye-related conditions like contact lens discomfort, yet currently we know little regarding the overall efficacy of individual, commercially available artificial tears. This review provides a much needed meta-analytical look at all randomized and quasi randomized clinical trials that have analyzed head-to-head comparisons of OTC artificial tears. OBJECTIVES: To evaluate the effectiveness and toxicity of OTC artificial tear applications in the treatment of dry eye syndrome compared with another class of OTC artificial tears, no treatment, or placebo. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2015, Issue 12), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to December 2015), EMBASE (January 1980 to December 2015), Latin American and Caribbean Health Sciences (LILACS) (January 1982 to December 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en) and the US Food and Drugs Administration (FDA) website (www.fda.gov). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 4 December 2015. We searched reference lists of included trials for any additional trials not identified by the electronic searches. SELECTION CRITERIA: This review includes randomized controlled trials with adult participants who were diagnosed with dry eye, regardless of race and gender. We included trials in which the age of participants was not reported, and clinical trials comparing OTC artificial tears with another class of OTC artificial tears, placebo, or no treatment. This review did not consider head-to-head comparisons of artificial tears with another type of dry-eye therapy. DATA COLLECTION AND ANALYSIS: We followed the standard methodological procedures expected by Cochrane. Two authors independently screened the search results, reviewed full text copies for eligibility, examined risk of bias, and extracted data. We performed meta-analysis for trials that compared similar interventions and reported comparable outcomes with sufficient data. We summarized all other included trial results in the text. MAIN RESULTS: We included 43 randomized controlled trials (3497 participants with dry eye). Due to the heterogeneity of study characteristics among the included trials with respect to types of diagnostic criteria, interventions, comparisons, and measurements taken, our ability to perform meta-analyses was limited. The review found that, in general, there was uncertainty whether different OTC artificial tears provide similar relief of signs and symptoms when compared with each other or placebo. Nevertheless, we found that 0.2% polyacrylic acid-based artificial tears were consistently more effective at treating dry eye symptoms than 1.4% polyvinyl alcohol-based artificial tears in two trials assessing this comparison (175 participants). All other included artificial tears produced contradictory between group results or found no between-group differences. Our review also found that OTC artificial tears may be generally safe, but not without adverse events. Overall, we assessed the quality of evidence as low due to high risks of bias among included trials and poor reporting of outcome measures which were insufficient for quantitative analysis. Furthermore, we identified an additional 18 potentially eligible trials that were reported only in clinical trial registers with no associated results or publications. These trials reportedly enrolled 2079 total participants for whom no data are available. Such lack of reporting of trial results represents a high risk of publication bias. AUTHORS' CONCLUSIONS: OTC artificial tears may be safe and effective means for treating dry eye syndrome; the literature indicates that the majority of OTC artificial tears may have similar efficacies. This conclusion could be greatly skewed by the inconsistencies in study designs and inconsistencies in reporting trial results. Additional research is therefore needed before we can draw robust conclusions about the effectiveness of individual OTC artificial tear formulations. PMID- 26905378 TI - Exercise mitigates mitochondrial permeability transition pore and quality control mechanisms alterations in nonalcoholic steatohepatitis. AB - Mitochondrial quality control and apoptosis have been described as key components in the pathogenesis of nonalcoholic steatohepatitis (NASH); exercise is recognized as a nonpharmacological strategy to counteract NASH-associated consequences. We aimed to analyze the effect of voluntary physical activity (VPA) and endurance training (ET) against NASH-induced mitochondrial permeability transition pore (mPTP) opening and mitochondrial and cellular quality control deleterious alterations. Forty-eight male Sprague-Dawley rats were divided into standard-diet sedentary (SS, n = 16), standard-diet VPA (n = 8), high-fat diet sedentary (HS, n = 16), and high-fat diet VPA (n = 8). After 9 weeks of diet treatment, half of the SS and HS groups were engaged in an ET program for 8 weeks, 5 days/week, 1 h/day. Liver mPTP susceptibility through osmotic swelling, mPTP-related proteins (cyclophilin D, Sirtuin3, Cofilin-1), markers of mitochondrial biogenesis ((mitochondrial transcription factor A (Tfam) and peroxisome proliferator-activated receptor gamma co-activator protein (PGC 1alpha)), dynamics (Mitofusin 1 (Mfn1), Mitofusin 2 (Mfn2), Dynamin related protein 1, and Optic atrophy 1)), auto/mitophagy (Beclin-1, microtubule associated protein 1 light chain 3, p62, PINK1, and Parkin), and apoptotic signaling (Bax, Bcl-2) and caspases-like activities were assessed. HS animals showed an increased susceptibility to mPTP, compromised expression of Tfam, Mfn1, PINK1, and Parkin and an increase in Bax content (HS vs. SS). ET and VPA improved biogenesis-related proteins (PGC-1alpha) and autophagy signaling (Beclin-1 and Beclin-1/Bcl-2 ratio) and decreased apoptotic signaling (caspases 8 activity, Bax content, and Bax/Bcl-2 ratio). However, only ET decreased mPTP susceptibility and positively modulated Bcl-2, Tfam, Mfn1, Mfn2, PINK1, and Parkin content. In conclusion, exercise reduces the increased susceptibility to mPTP induced by NASH and promotes the increase of auto/mitophagy and mitochondrial fusion towards a protective phenotype. PMID- 26905379 TI - Approaches to a cortical vision prosthesis: implications of electrode size and placement. AB - OBJECTIVE: In order to move forward with the development of a cortical vision prosthesis, the critical issues in the field must be identified. APPROACH: To begin this process, we performed a brief review of several different cortical and retinal stimulation techniques that can be used to restore vision. MAIN RESULTS: Intracortical microelectrodes and epicortical macroelectrodes have been evaluated as the basis of a vision prosthesis. We concluded that an important knowledge gap necessitates an experimental in vivo performance evaluation of microelectrodes placed on the surface of the visual cortex. A comparison of the level of vision restored by intracortical versus epicortical microstimulation is necessary. Because foveal representation in the primary visual cortex involves more cortical columns per degree of visual field than does peripheral vision, restoration of foveal vision may require a large number of closely spaced microelectrodes. Based on previous studies of epicortical macrostimulation, it is possible that stimulation via surface microelectrodes could produce a lower spatial resolution, making them better suited for restoring peripheral vision. SIGNIFICANCE: The validation of epicortical microstimulation in addition to the comparison of epicortical and intracortical approaches for vision restoration will fill an important knowledge gap and may have important implications for surgical strategies and device longevity. It is possible that the best approach to vision restoration will utilize both epicortical and intracortical microstimulation approaches, applying them appropriately to different visual representations in the primary visual cortex. PMID- 26905380 TI - Brain processes in women and men in response to emotive sounds. AB - Adult appropriate responding to salient infant signals is vital to child healthy psychological development. Here we investigated how infant crying, relative to other emotive sounds of infant laughing or adult crying, captures adults' brain resources. In a sample of nulliparous women and men, we investigated the effects of different sounds on cerebral activation of the default mode network (DMN) and reaction times (RTs) while listeners engaged in self-referential decision and syllabic counting tasks, which, respectively, require the activation or deactivation of the DMN. Sounds affect women and men differently. In women, infant crying deactivated the DMN during the self-referential decision task; in men, female adult crying interfered with the DMN during the syllabic counting task. These findings point to different brain processes underlying responsiveness to crying in women and men and show that cerebral activation is modulated by situational contexts in which crying occurs. PMID- 26905381 TI - Individual Apostichopus japonicus fecal microbiome reveals a link with polyhydroxybutyrate producers in host growth gaps. AB - Gut microbiome shapes various aspects of a host's physiology, but these functions in aquatic animal hosts have yet to be fully investigated. The sea cucumber Apostichopus japonicus Selenka is one such example. The large growth gap in their body size has delayed the development of intensive aquaculture, nevertheless the species is in urgent need of conservation. To understand possible contributions of the gut microbiome to its host's growth, individual fecal microbiome comparisons were performed. High-throughput 16S rRNA sequencing revealed significantly different microbiota in larger and smaller individuals; Rhodobacterales in particular was the most significantly abundant bacterial group in the larger specimens. Further shotgun metagenome of representative samples revealed a significant abundance of microbiome retaining polyhydroxybutyrate (PHB) metabolism genes in the largest individual. The PHB metabolism reads were potentially derived from Rhodobacterales. These results imply a possible link between microbial PHB producers and potential growth promotion in Deuterostomia marine invertebrates. PMID- 26905382 TI - Comparative transcriptome analysis of fruiting body and sporulating mycelia of Villosiclava virens reveals genes with putative functions in sexual reproduction. AB - Sexual reproduction of heterothallic clavicipitaceous fungus Villosiclava virens (anamorph: Ustilaginoidea virens) generates ascospores, which is considered as primary infection source of rice false smut disease. However, little is known about the molecular underpinnings of sexual reproduction in V. virens. In this study, transcriptomes of V. virens in fruiting body (FB) and sporulating mycelia (SM) were compared using Illumina paired-end sequencing technology. A total of 33,384,588 and 23,765,275 clean reads of FB and SM transcriptome profiles could be used to map cDNA of V. virens, respectively. We evaluated the gene expression variations between FB and SM, a total of 488 genes therein were significantly higher expressed in FB than SM, and 342 genes were significantly higher expressed genes in SM than FB. These differentially expressed genes were annotated using Kyoto Encyclopedia of Genes and Genomes and Gene Ontology databases. Several genes were found to specifically function in sexual reproduction, involving in mating type, pheromone synthesis, signaling transduction, transcription factors, and meiosis; additionally, a few of genes were presumed to function in conidia sporulation and infection. Comparative transcriptome analysis of V. virens during FB and SM provided an overview of gene expression profiles at the transcriptional level and provided hints to better understand the molecular mechanisms of sexual development. Additionally, the data presented here also proved benefit for mining of essential genes contributing to sexual conidiation and infection. PMID- 26905383 TI - Temozolomide-loaded PLGA nanoparticles to treat glioblastoma cells: a biophysical and cell culture evaluation. AB - OBJECTIVES: Current chemotherapies for brain glioblastoma do not achieve sufficient drug concentrations within tumors. Polymeric nanoparticles have useful physicochemical properties that make them promising as nanoparticle platforms for glioblastoma drug delivery. Poly[lactic-co-glycolic acid] (PLGA) nanoparticles encapsulating temozolomide (TMZ) could improve localized delivery and sustained drug release to glioblastomas. METHODS: We investigated three different procedures to encapsulate TMZ within PLGA nanoparticles. We studied the biophysical features of optimized nanocarriers, including their size, shape, surface properties, and release characteristics of TMZ. We evaluated the antiproliferative and cytotoxic effects of TMZ-loaded PLGA nanoparticles on U87 MG glioblastoma cells. RESULTS: A single emulsion technique using a TMZ saturated aqueous phase produced nanoparticles <=200 nm in size allowing a maximal drug loading of 4.4% w/w of polymer. There was a bi-phasic drug release pattern, with 80% of TMZ released within the first 6 h. Nanoparticles accumulated in the cytoplasm after effective endocytosis. There was no significant difference in cytotoxic effect of TMZ encapsulated within PLGA nanoparticles and free TMZ. CONCLUSIONS: PLGA nanoparticles are not suitable as carriers of TMZ for glioblastoma drug delivery on account of the overall high IC50 values of glioblastoma cells to TMZ and poor loading and encapsulation efficiencies. Further biotechnological developments aimed at improving the loading of TMZ in PLGA nanoparticles or co-delivery of small molecule sensitizers to improve the response of human glioblastoma cells to TMZ are required for this approach to be considered and optimized for future clinical translation. PMID- 26905384 TI - An in vitro dynamic microcosm biofilm model for caries lesion development and antimicrobial dose-response studies. AB - Some dynamic biofilm models for dental caries development are limited as they require multiple experiments and do not allow independent biofilm growth units, making them expensive and time-consuming. This study aimed to develop and test an in vitro dynamic microcosm biofilm model for caries lesion development and for dose-response to chlorhexidine. Microcosm biofilms were grown under two different protocols from saliva on bovine enamel discs for up to 21 days. The study outcomes were as follows: the percentage of enamel surface hardness change, integrated hardness loss, and the CFU counts from the biofilms formed. The measured outcomes, mineral loss and CFU counts showed dose-response effects as a result of the treatment with chlorhexidine. Overall, the findings suggest that biofilm growth for seven days with 0.06 ml min(-1) salivary flow under exposure to 5% sucrose (3 * daily, 0.25 ml min(-1), 6 min) was suitable as a pre-clinical model for enamel demineralization and antimicrobial studies. PMID- 26905385 TI - Hydrogen Recombination and Dimer Formation on Graphite from Ab Initio Molecular Dynamics Simulations. AB - We studied Eley-Rideal molecular hydrogen formation on graphite using ab initio molecular dynamics, in the energy range relevant for the chemistry of the interstellar medium and for terrestrial experiments employing cold plasma (0.02-1 eV). We found substantial projectile steering effects that prevent dimer formation at low energies, thereby ruling out any catalytic synthetic pathways that form hydrogen molecules. Ortho and para dimers do form efficiently thanks to preferential sticking, but only at energies that are too high to be relevant for the chemistry of the interstellar medium. Computed reaction cross sections and ro vibrational product populations are in good agreement with available experimental data and capable of generating adsorbate configurations similar to those observed with scanning tunneling microscopy techniques. PMID- 26905386 TI - A case of phakomatosis pigmentovascularis type II: port-wine stain and dermal melanocytosis with cutis marmorata telangiectatica congenita-like lesions. PMID- 26905387 TI - A meta-analysis of brief alcohol interventions for adolescents and young adults: variability in effects across alcohol measures. AB - BACKGROUND: Brief alcohol interventions are one approach for reducing drinking among youth, but may vary in effectiveness depending on the type of alcohol assessments used to measure effects. OBJECTIVES: To conduct a meta-analysis that examined the effectiveness of brief alcohol interventions for adolescents and young adults, with particular emphasis on exploring variability in effects across outcome measurement characteristics. METHOD: Eligible studies were those using an experimental or quasi-experimental design to examine the effects of a brief alcohol intervention on a post-intervention alcohol use measure for youth aged 11 30. A comprehensive literature review identified 190 unique samples that were included in the meta-analysis. Taking a Bayesian approach, we used random-effects multilevel models to estimate the average effect and model variability across outcome measurement types. RESULTS: Brief alcohol interventions led to significant reductions in self-reported alcohol use among adolescents (g = 0.25, 95% credible interval [CrI 0.13, 0.37]) and young adults (g = 0.15, 95% CrI [0.12, 0.18]). These results were consistent across outcomes with varying reference periods, but varied across outcome construct type and assessment instruments. Among adolescents, effects were larger when measured using the Timeline Followback; among young adults, effects were smaller when measured using the Alcohol Use Disorders Identification Test. CONCLUSION: The strength of the beneficial effects of brief alcohol interventions on youth's alcohol use may vary depending upon the outcome measure utilized. Nevertheless, significant effects were observed across measures. Although effects were modest in size, they were clinically significant and show promise for interrupting problematic alcohol use trajectories among youth. PMID- 26905388 TI - The Effect of Head Up Cardiopulmonary Resuscitation on Cerebral and Systemic Hemodynamics. AB - AIM: Chest compressions during cardiopulmonary resuscitation (CPR) increase arterial and venous pressures, delivering simultaneous bidirectional high pressure compression waves to the brain. We hypothesized that this may be detrimental and could be partially overcome by elevation of the head during CPR. MEASUREMENTS: Female Yorkshire farm pigs (n=30) were sedated, intubated, anesthetized, and placed on a table able to elevate the head 30 degrees (15cm) (HUP) and the heart 10 degrees (4cm) or remain in the supine (SUP) flat position during CPR. After 8minutes of untreated ventricular fibrillation and 2minutes of SUP CPR, pigs were randomized to HUP or SUP CPR for 20 more minutes. In Group A, pigs were randomized after 2minutes of flat automated conventional (C) CPR to HUP (n=7) or SUP (n=7) C-CPR. In Group B, pigs were randomized after 2minutes of automated active compression decompression (ACD) CPR plus an impedance threshold device (ITD) SUP CPR to either HUP (n=8) or SUP (n=8). RESULTS: The primary outcome of the study was difference in CerPP (mmHg) between the HUP and SUP positions within groups. After 22minutes of CPR, CerPP was 6+/-3mmHg in the HUP versus -5+/-3 in the SUP (p=0.016) in Group A, and 51+/-8 versus 20+/-5 (p=0.006) in Group B. Coronary perfusion pressures after 22minutes were HUP 6+/-2 vs SUP 3+/-2 (p=0.283) in Group A and HUP 32+/-5 vs SUP 19+/-5, (p=0.074) in Group B. In Group B, 6/8 pigs were resuscitated in both positions. No pigs were resuscitated in Group A. CONCLUSIONS: The HUP position in both C-CPR and ACD+ITD CPR significantly improved CerPP. This simple maneuver has the potential to improve neurological outcomes after cardiac arrest. PMID- 26905389 TI - The ability of early warning scores (EWS) to detect critical illness in the prehospital setting: A systematic review. AB - AIM: To examine whether early warning scores (EWS) can accurately predict critical illness in the prehospital setting and affect patient outcomes. METHODS: We searched bibliographic databases for comparative studies that examined prehospital EWS for patients transported by ambulance in the prehospital setting. The ability of the different EWS, including pre-alert protocols and physiological based EWS, to predict critical illness (sensitivity, odds ratio [OR], area under receiver operating characteristic [AUROC] curves) and hospital mortality was summarised. Study quality was assessed using the Newcastle-Ottawa Scale. RESULTS: Eight studies were identified. Two studies compared the use of EWS to standard practice using clinical judgement alone to identify critical illness: the pooled diagnostic OR and summary AUROC for EWS were 10.9 (95%CI 4.2-27.9) and 0.78 (95%CI 0.74-0.82), respectively. A study of 144,913 patients reported age and physiological variables predictive of critical illness: AUROC in the independent validation sample was 0.77, 95% CI 0.76-0.78. The high-risk patients stratified by the national early warning score (NEWS) were significantly associated with a higher risk of both mortality and intensive care admission. Data on comparing between different EWS were limited; the Prehospital Early Sepsis Detection (PRESEP) score predicted occurrence of sepsis better than the Modified EWS (AUROC 0.93 versus 0.77, respectively). CONCLUSION: EWS in the prehospital setting appeared useful in predicting clinically important outcomes, but the significant heterogeneity between different EWS suggests that these positive promising findings may not be generalisable. Adequately powered prospective studies are needed to identify the EWS best suited to the prehospital setting. PMID- 26905390 TI - Plumbagin, Juglone, and Boropinal as Novel TRPA1 Agonists. AB - A series of seven oxyprenylated phenylpropanoids and naphthoquinones were tested regarding their ability to activate transient receptor potential ankyrin subtype 1 channel (TRPA1). Three of the assayed compounds, namely, boropinal (3), juglone (5), and plumbagin (7), acted as strong modulators of TRPA1 channels with EC50 values of 9.8, 1.7, and 0.5 MUM, respectively, as assessed by Ca(2+) assays. Moreover, the compounds elicited TRPA1 currents in electrophysiological whole cell recordings. We additionally provide evidence that plumbagin activated TRPA1 positive neurons isolated from mouse dorsal root ganglion neurons but did not affect sensory neurons from TRPA1-deficient mice. The high potencies of plumbagin and juglone to activate TRPA1 channels may explain the molecular basis of the mucosal irritant properties of these compounds as well as of related naphthoquinones and phytopreparations, as widely reported in the literature. PMID- 26905392 TI - Optimizing hepatitis B vaccination in prison. AB - OBJECTIVE: We aimed to establish the current status of hepatitis B virus (HBV) vaccination in prison. METHODS: We carried out two evaluations within a 1-year interval with inmates incarcerated for 6 to 12 months. A monitoring process was introduced in-between the two evaluations. RESULTS: We included 231 inmates. Overall, 42.9% were immunized because of a previous vaccination and 14.3% because of a previous exposure. Inmates born in an area of medium or high endemicity for HBV were significantly more exposed to HBV. The proportion of non-immunized inmates was 42.8% at the time of incarceration and 27.5% after 6 to 12 months. Vaccination coverage with two doses, after 6 to 12 months, was 63% among patients who were initially non-immunized. CONCLUSION: The recently developed accelerated vaccination schedule should help improve HBV vaccination coverage. PMID- 26905391 TI - Structural hot spots for the solubility of globular proteins. AB - Natural selection shapes protein solubility to physiological requirements and recombinant applications that require higher protein concentrations are often problematic. This raises the question whether the solubility of natural protein sequences can be improved. We here show an anti-correlation between the number of aggregation prone regions (APRs) in a protein sequence and its solubility, suggesting that mutational suppression of APRs provides a simple strategy to increase protein solubility. We show that mutations at specific positions within a protein structure can act as APR suppressors without affecting protein stability. These hot spots for protein solubility are both structure and sequence dependent but can be computationally predicted. We demonstrate this by reducing the aggregation of human alpha-galactosidase and protective antigen of Bacillus anthracis through mutation. Our results indicate that many proteins possess hot spots allowing to adapt protein solubility independently of structure and function. PMID- 26905393 TI - Accurate MALDI-TOF mass spectrometry identification of a colistin-resistant Moellerella wisconsensis strain. PMID- 26905394 TI - Generic antiretroviral drugs and HIV care: An economic review. AB - The cost of HIV care in European countries is high. Direct medical costs, in France, have been estimated at 500,000 Euros per patient's lifetime (20,000 Euros/year/patient). Overall, 73% of these costs are related to antiretroviral treatments. In the current financial crisis context, some European countries are beginning to make economic decisions on the drugs to be used. These approaches are likely to become more frequent. It is obviously essential to prescribe the most effective, appropriate, best tolerated, and easy-to-use antiretroviral treatments to patients. However, while taking the above into consideration, and if various treatment options or combinations are available, cost should also be considered in the treatment choice. One may thus reflect on the use of generic antiretroviral agents as they have just been launched in France. We aimed to review the cost and cost-effectiveness of generic antiretroviral drugs and to review treatment strategies other than generic drugs that could help reduce HIV related costs. HIV clinicians should consider treatment costs to avoid any future coercive measures. PMID- 26905395 TI - Cellulosimicrobium marinum sp. nov., an actinobacterium isolated from sea sediment. AB - A novel Gram stain positive actinobacterium, designated RS-7-4(T), was isolated from a sea sediment sample collected in Indonesia, and its taxonomic position was investigated using a polyphasic approach. Strain RS-7-4(T) was observed to form vegetative hyphae in the early phase of growth, but the hyphae eventually fragmented into short rods to coccoid cells. Growth occurred at 15-37 degrees C, pH 6.0-11.0 and in the presence of 0-7 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequence comparisons revealed that strain RS-7-4(T) was closely related to the members of the genus Cellulosimicrobium, with a similarity range of 98.08-99.10 %. The peptidoglycan type of strain RS-7-4(T) was found to be A4alpha L-Lys-L-Thr-D-Asp. The predominant menaquinone was MK-9(H4), and the major fatty acids were anteiso-C15:0, iso-C15:0 and anteiso-C17:0. The DNA G+C content was 75.6 mol%. These chemotaxonomic features corresponded to those of the genus Cellulosimicrobium. Meanwhile, the results of DNA-DNA hybridization, and physiological and biochemical tests revealed that strain RS-7-4(T) was different from the recognized species of the genus Cellulosimicrobium. Therefore, strain RS 7-4(T) represents a novel species of the genus Cellulosimicrobium, for which the name Cellulosimicrobium marinum sp. nov. is proposed. The type strain is RS-7 4(T) (=NBRC 110994(T) =InaCC A726(T)). PMID- 26905396 TI - An evaluation of the feasibility and usability of a proof of concept mobile app for adverse event reporting post influenza vaccination. AB - The Canadian National Vaccine Safety network (CANVAS) gathers and analyzes safety data on individuals receiving the influenza vaccine during the early stages of annual influenza vaccination campaigns with data collected via participant surveys through the Internet. We sought to examine whether it was feasible to use a mobile application (app) to facilitate AEFI reporting for the CANVAS network. To explore this, we developed a novel smartphone app, recruited participants from a hospital influenza immunization clinic and by word of mouth and instructed them to download and utilize the app. The app reminded participants to complete the CANVAS AEFI surveillance surveys ("AEFI surveys") on day 8 and 30, a survey capturing app usability metrics at day 30 ("usability survey") and provided a mechanism to report AEFI events spontaneously throughout the whole study period. All survey results and spontaneous reports were recorded on a privacy compliant, cloud server. A software plug-in, Lookback, was used to record the on-screen experience of the app sessions. Of the 76 participants who consented to participate, 48(63%) successfully downloaded the app and created a profile. In total, 38 unique participants completed all of the required surveillance surveys; transmitting 1104 data points (survey question responses and spontaneous reports) from 83 completed surveys, including 21 usability surveys and one spontaneous report. In total, we received information on new or worsening health conditions after receiving the influenza vaccine from 11(28%) participants. Of the usability survey responses, 86% agreed or strongly agreed that they would prefer to use a mobile app based reporting system instead of a web-based system. The single spontaneous report received was from a participant who had also reported using the Day 8 survey. Of Lookback observable sessions, an accurate transmission proportion of 100% (n=290) was reported for data points. We demonstrated that a mobile app can be used for AEFI reporting, although download and survey completion proportions suggest potential barriers to adoption. Future studies should examine implementation of mobile reporting in a broader audience and impact on the quality of reporting of adverse events following immunization. PMID- 26905401 TI - The meaning of seasonal changes, nature, and animals for adolescent girls' wellbeing in northern Finland: A qualitative descriptive study. AB - Wellbeing is complex, holistic, and subjectively perceived. Issues such as gender, age, and environment seem to affect it. Therefore, the aim of this qualitative study was to describe the meaning of seasonal changes, nature, and animals towards 13-16-year-old girls' wellbeing in Northern Finland. In the spring of 2014, through purposive sampling, a total of 19 girls participated in semi-structured interviews from various parts of Northern Finland. The data were analysed using content analysis. Afterwards, the analysis combining the category participatory involvement with environment was found, and this consisted of three main categories: adaptation to seasonal changes, restorative nature, and empowering interactivity with animals. Seasonal changes had an effect on girls' wellbeing; in the summertime, they felt happy and vivacious, active, and outgoing. Instead, during the winter months, girls' mood and activity seemed to be lower and they felt lazier and depressed. Nature brought mainly positive feelings to girls; being in nature was experienced as liberating and relaxing, and it offered opportunities to relax and have sensory perceptions. Interaction with animals was perceived as empowering. They were experienced as altruistic and comforting companions. Animals were important to girls, and they contributed to girls' lives through positive effects towards their mental and physical wellbeing. Based on the results of this study, we can recommend that being in nature and interacting with animals should be supported because they seem to have benefits towards adolescent girls' health and wellbeing. In order to facilitate the negative effects of winter, the school days should be arranged in such a way that it would be possible for girls to have outdoor activities during the daytime. The challenge for the future is perhaps the purposeful utilisation of nature's and the animals' positive effects towards their wellbeing. PMID- 26905402 TI - Colorectal cancer prevention: Perspectives of key players from social networks in a low-income rural US region. AB - Social networks influence health behavior and health status. Within social networks, "key players" often influence those around them, particularly in traditionally underserved areas like the Appalachian region in the USA. From a total sample of 787 Appalachian residents, we identified and interviewed 10 key players in complex networks, asking them what comprises a key player, their role in their network and community, and ideas to overcome and increase colorectal cancer (CRC) screening. Key players emphasized their communication skills, resourcefulness, and special occupational and educational status in the community. Barriers to CRC screening included negative perceptions of the colonoscopy screening procedure, discomfort with the medical system, and misinformed perspectives on screening. Ideas to improve screening focused on increasing awareness of women's susceptibility to CRC, providing information on different screening tests, improving access, and the key role of health-care providers and key players themselves. We provide recommendations to leverage these vital community resources. PMID- 26905403 TI - From proteomics to personalized medicine: the road ahead. PMID- 26905404 TI - Modeling the cost-effectiveness of infant vaccination with pneumococcal conjugate vaccines in Germany. AB - BACKGROUND: In 2009, the European Medicines Agency granted approval for two higher-valent pneumococcal conjugate vaccines. This study aims to evaluate the cost-effectiveness of universal infant (<2 years old) vaccination with a 13 valent pneumococcal conjugate vaccine (PCV13) in comparison with a 10-valent pneumococcal conjugate vaccine (PCV10) for the prevention of pneumococcal disease in Germany. METHODS: A population-based Markov model was developed to estimate the impact of PCV13 and PCV10 on invasive pneumococcal disease (IPD), non invasive pneumonia (PNE), and acute otitis media (AOM) over a time horizon of 50 years. The model included the effects of the historical vaccination scheme in infants as well as indirect herd effects and replacement disease. We used German epidemiological data to calculate episodes of IPD, PNE, and AOM, as well as direct and indirect effects of the vaccination. Parameter uncertainty was tested in univariate and probabilistic sensitivity analyses. RESULTS: In the base-case analysis, the ICER of PCV13 versus PCV10 infant vaccination was EUR 9826 per quality-adjusted life-year (QALY) gained or EUR 5490 per life-year (LY) gained from the societal perspective and EUR 3368 per QALY gained or EUR 1882 per LY gained from the perspective of the German statutory health insurance. The results were particularly sensitive to the magnitude of indirect effects of both vaccines. CONCLUSIONS: Universal infant vaccination with PCV13 is likely to be a cost-effective intervention compared with PCV10 within the German health care system, if additional net indirect effects of PCV13 vaccination are significant. PMID- 26905405 TI - Atrial electromechanical delay and left atrial mechanical functions in hemodialysis and peritoneal dialysis patients. AB - INTRODUCTION: Left atrium (LA) mechanical functions and atrial electromechanical delay (AEMD) times were considered independent predictors of cardiovascular morbidity in general population. Data are scant about these parameters in end stage renal disease (ESRD) patients receiving hemodialysis (HD) and peritoneal dialysis (PD). We aimed to evaluate AEMD times and LA mechanical functions and associated risk factors in HD and PD patients. METHODS: Forty-four healthy individuals, 62 HD and 50 PD patients were enrolled in the study. Echocardiography was performed before midweek dialysis session for HD patients and on admission for PD patients. Data were expressed as mean +/- SD. Spearman's test was used to assess linear associations. Predictors of left intra-atrial EMD time and LA active emptying volume (LAaeV) were assessed by regression analysis. RESULTS: Left intra-atrial-AEMD times were significantly longer in HD patients compared to PD patients. LAaeV was positively correlated with inter-atrial time, left intra-atrial time, systolic and diastolic BP, calcium and neutrophil-to lymphocyte ratio (NLR) (r 0.22, p 0.016; r 0.28, p 0.002; r 0.34, p < 0.001; r 0.35, p < 0.001; r 0.37, p < 0.001; r 0.46, p < 0.001, respectively) and negatively correlated with serum uric acid (r -0.31, p 0.013) in ESRD patients. We found positive correlations between left intra-atrial time and LAaeV, LAVmax, LAVp and NLR (r 0.28, p 0.002; r 0.27, p 0.003; r 0.27, p 0.003; r 0.22, p 0.03, respectively) and negative correlations with albumin, uric acid and potassium (r 0.24, p 0.008; r -0.19, p 0.04; r -0.26, p 0.037, respectively). Advanced age, decreased serum albumin and increased NLR were found to be independent predictors of LAaeV; however, only NLR was found to be an independent predictor of AEMD time in this population. CONCLUSIONS: Increased inflammation might be a risk factor of AEMD and LA mechanical dysfunction in ESRD patients. PMID- 26905406 TI - Estimated glomerular filtration rate and albuminuria in Korean population evaluated for cardiovascular risk. AB - PURPOSE: This study's purpose was to examine established cardiovascular risk prediction model scores for their associations with albuminuria and estimated glomerular filtration rate (eGFR) in Korean population. METHODS: We calculated the 10-year atherosclerotic cardiovascular disease (ASCVD) risk estimated score, Korean coronary heart disease risk prediction score (KRS), and the Adult Treatment Panel (ATP) III risk score for 9733 South Koreans, aged 40-79 years, who were not diagnosed with stroke, angina pectoris, or myocardial ischemia using data from the 2011-2013 Korea National Health and Nutrition Examination Survey. RESULTS: The associations between cardiovascular risk model scores and the urine albumin-to-creatinine ratio (UACR) and eGFR tended to be stronger for the ASCVD risk score than for the other risk scores. The area under the receiver operating characteristic curve for increased albuminuria (UACR >= 30 mg/g) and decreased eGFR (<60 mL/min/1.73 m(2)) was significantly higher for the ASCVD risk score than for the ATP III risk score and the KRS (except for increased albuminuria in women). CONCLUSIONS: The ASCVD risk score had a stronger relationship with and better predicted albuminuria and eGFR than did the KRS and ATP III risk score. PMID- 26905407 TI - Correlation between nonalcoholic fatty liver and cardiovascular disease in elderly hemodialysis patients. AB - PURPOSE: The number of elderly patients with end-stage kidney disease is on the rise. Nonalcoholic fatty liver disease (NAFLD) is characterized by parenchymal fat accumulation in patients without information about alcohol abuse. The aim of our study was to determine correlation between NAFLD and cardiovascular diseases in elderly hemodialysis patients. METHODS: The examination was organized as observational and cross-sectional study in elderly patients on hemodialysis. An abdominal ultrasound examination was made in order to define NAFLD. Intima-media thickness of the carotid arteries was quantified by Doppler ultrasound. Biochemical parameters, gender, anthropometric characteristics, duration, adequacy of hemodialysis, blood pressure, smoking and cardiovascular disease were determined. Respondents were divided into a group with NAFLD (37/72 patients, 51 %) and group without NAFLD (35/72 patients, 49 %). RESULTS: Patients with NAFLD have significantly more cardiovascular disease (p = 0.017) as well as significantly higher values of intima-media thickness of the carotid arteries (p = 0.03) in correlation with patients without NAFLD. Patients without NAFLD have a statistically lower triglyceride (p = 0.04), aspartate aminotransferase (p = 0.006), alanine aminotransferase (p = 0.013) and gamma-glutamyl transpeptidase (p = 0.029) compared to patients with NAFLD. Patients with cardiovascular disease have a higher risk of NAFLD; likewise, patients with NAFLD have a three times higher chance for developing cardiovascular diseases (OR 3.01). CONCLUSION: Elderly patients on hemodialysis with cardiovascular disease have a higher risk of NAFLD; likewise, patients with NAFLD have a three times higher chance for developing cardiovascular diseases. PMID- 26905410 TI - A numerical study to determine the effect of ligament stiffness on kinematics of the lumbar spine during flexion. AB - BACKGROUND: There is a wide range of mechanical properties of spinal ligaments documented in literature. Due to the fact that ligaments contribute in stabilizing the spine by limiting excessive intersegmental motion, those properties are of particular interest for the implementation in musculoskeletal models. The aim of this study was to investigate the effect of varying ligament stiffness on the kinematic behaviour of the lumbar spine. METHODS: A musculoskeletal model with a detailed lumbar spine was modified according to fluoroscopic recordings and corresponding data files of three different subjects. For flexion, inverse dynamics analysis with a variation of the ligament stiffness matrix were conducted. The influence of several degrees of ligament stiffness on the lumbar spine model were investigated by tracking ligament forces, disc forces and resulting moments generated by the ligaments. Additionally, the kinematics of the motion segments were evaluated. RESULTS: An increase of ligament stiffness resulted in an increase of ligament and disc forces, whereas the relative change of disc force increased at a higher rate at the L4/L5 level (19 %) than at the L3/L4 (10 %) level in a fully flexed posture. The same behaviour applied to measured moments with 67 % and 45 %. As a consequence, the motion deflected to the lower levels of the lumbar spine and the lower discs had to resist an increase in loading. CONCLUSIONS: Higher values of ligament stiffness over all lumbar levels could lead to a shift of the loading and the motion between segments to the lower lumbar levels. This could lead to an increased risk for the lower lumbar parts. PMID- 26905408 TI - Validation of a novel prediction model for early mortality in adult trauma patients in three public university hospitals in urban India. AB - BACKGROUND: Trauma is one of the top threats to population health globally. Several prediction models have been developed to supplement clinical judgment in trauma care. Whereas most models have been developed in high-income countries the majority of trauma deaths occur in low- and middle-income countries. Almost 20 % of all global trauma deaths occur in India alone. The aim of this study was to validate a basic clinical prediction model for use in urban Indian university hospitals, and to compare it with existing models for use in early trauma care. METHODS: We conducted a prospective cohort study in three hospitals across urban India. The model we aimed to validate included systolic blood pressure and Glasgow coma scale. We compared this model with three additional models, which all have been designed for use in bedside trauma care, and two single variable models based on systolic blood pressure and Glasgow coma scale respectively. The outcome was early mortality, defined as death within 24 h from the time when vital signs were first measured. We compared the models in terms of discrimination, calibration, and potential clinical consequences using decision curve analysis. Multiple imputation was used to handle missing data. Performance measures are reported using their median and inter-quartile range (IQR) across imputed datasets. RESULTS: We analysed 4440 patients, out of which 1629 were used as an updating sample and 2811 as a validation sample. We found no evidence that the basic model that included only systolic blood pressure and Glasgow coma scale had worse discrimination or potential clinical consequences compared to the other models. A model that also included heart had better calibration. For the model with systolic blood pressure and Glasgow coma scale the discrimination in terms of area under the receiver operating characteristics curve was 0.846 (IQR 0.841 0.849). Calibration measured by estimating a calibration slope was 1.183 (IQR 1.168-1.202). Decision curve analysis revealed that using this model could potentially result in 45 fewer unnecessary surveys per 100 patients. CONCLUSIONS: A basic clinical prediction model with only two parameters may prove to be a feasible alternative to more complex models in contexts such as the Indian public university hospitals studied here. We present a colour-coded chart to further simplify the decision making in early trauma care. PMID- 26905411 TI - Antipsychotic pharmacogenomics in first episode psychosis: a role for glutamate genes. AB - Genetic factors may underlie beneficial and adverse responses to antipsychotic treatment. These relationships may be easier to identify among patients early in the course of disease who have limited exposure to antipsychotic drugs. We examined 86 first episode patients (schizophrenia, psychotic bipolar disorder and major depressive disorder with psychotic features) who had minimal to no prior antipsychotic exposure in a 6-week pharmacogenomic study of antipsychotic treatment response. Response was measured by change in Brief Psychiatric Rating Scale total score. Risperidone monotherapy was the primary antipsychotic treatment. Pharmacogenomic association studies were completed to (1) examine candidate single-nucleotide polymorphisms (SNPs) in genes known to be involved with glutamate signaling, and (2) conduct an exploratory genome-wide association study of symptom response to identify potential novel associations for future investigation. Two SNPs in GRM7 (rs2069062 and rs2014195) were significantly associated with antipsychotic response in candidate gene analysis, as were two SNPs in the human glutamate receptor delta 2 (GRID2) gene (rs9307122 and rs1875705) in genome-wide association analysis. Further examination of these findings with those from a separate risperidone-treated study sample demonstrated that top SNPs in both studies were overrepresented in glutamate genes and that there were similarities in neurodevelopmental gene categories associated with drug response from both study samples. These associations indicate a role for gene variants related to glutamate signaling and antipsychotic response with more broad association patterns indicating the potential importance of genes involved in neuronal development. PMID- 26905412 TI - Dopamine cross-sensitization between psychostimulant drugs and stress in healthy male volunteers. AB - Dysregulation of the stress response system is a potential etiological factor in the development of and relapse to multiple neuropsychiatric disorders. Previously we reported that repeated intermittent d-amphetamine administration can lead to progressively greater dopamine release, thereby providing evidence of drug induced neurochemical sensitization. Here, we test the hypothesis that repeated exposure to d-amphetamine increases dopaminergic responses to stress; that is, produces cross-sensitization. Using positron emission tomography, we measured in 17 healthy male volunteers (mean +/- s.d. = 22.1 +/- 3.4 years) [(11)C]raclopride binding responses to a validated psychosocial stress task before and 2 weeks after a regimen of repeated d-amphetamine (3 * 0.3 mg kg(-1), by mouth; n = 8) or placebo (3 * lactose, by mouth; n = 9). Mood and physiological measurements were recorded throughout each session. Before the d-amphetamine regimen, exposure to the stress task increased behavioral and physiological indices of stress (anxiety, heart rate, cortisol, all P ? 0.05). Following the d-amphetamine regimen, the stress-induced cortisol responses were augmented (P < 0.04), and voxel-based analyses showed larger stress-induced decreases in [(11)C]raclopride non-displaceable binding potential across the striatum. In the placebo group, re exposure to stress led to smaller clusters of decreased [(11)C]raclopride binding, primarily in the sensorimotor striatum (P < 0.05). Together, this study provides evidence for drug * stress cross-sensitization; moreover, random exposure to stimulants and/or stress cumulatively, while enhancing dopamine release in striatal areas, may contribute to a lowered set point for psychopathologies in which altered dopamine neurotransmission is invoked. PMID- 26905413 TI - Role of hippocampal p11 in the sustained antidepressant effect of ketamine in the chronic unpredictable mild stress model. AB - Although ketamine shows a rapid and sustained antidepressant effect, the precise mechanisms underlying its effect are unknown. Recent studies indicate a key role of p11 (also known as S100A10) in depression-like behavior in rodents. The present study aimed to investigate the role of p11 in the antidepressant-like action of ketamine in chronic unpredictable mild stress (CUMS) rat model. The open-field test, forced swimming test and sucrose preference test were performed after administration of ketamine (10 mg kg(-1)) or a combination of ketamine and ANA-12 (a tropomyosin-related kinase B (TrkB) antagonist; 0.5 mg kg(-1)). The lentivirus vector for p11 was constructed to knock down the hippocampal expression of p11. In the CUMS rats, ketamine showed a rapid (0.5 h) and sustained (72 h) antidepressant effect, and its effect was significantly blocked by co-administration of ANA-12. Furthermore, ketamine significantly increased the reduced expression of brain-derived neurotrophic factor (BDNF) in the hippocampus of CUMS rats, whereas ketamine did not affect the expression of p11 in CUMS rats 0.5 h after administration. In addition, ketamine significantly increased the reduced ratio of p-TrkB/TrkB in the hippocampus by CUMS rats, and its effect was also blocked by ANA-12. Moreover, the reduced expression of BDNF and p11 in the hippocampus of CUMS rats was significantly recovered to control levels 72 h after ketamine administration. Interestingly, knockdown of hippocampal p11 caused increased immobility time and decreased sucrose preference, which were not improved by ketamine administration. These results suggest that p11 in the hippocampus may have a key role in the sustained antidepressant effect of ketamine in the CUMS model of depression. PMID- 26905414 TI - Novel, primate-specific PDE10A isoform highlights gene expression complexity in human striatum with implications on the molecular pathology of bipolar disorder. AB - Bipolar disorder is a highly heritable neuropsychiatric disorder affecting nearly 2.5% of the population. Prior genetic studies identified a panel of common and rare single-nucleotide polymorphisms associated with the disease that map to the first intron of the PDE10A gene. RNA sequencing of striatal brain tissue from bipolar and healthy control subjects identified a novel transcript of PDE10A, named PDE10A19, that codes for a PDE10A isoform with a unique N terminus. Genomic sequences that can encode the novel N terminus were conserved in other primates but not rodents. The RNA transcript was expressed at equal or greater levels in the human striatum compared with the two annotated transcripts, PDE10A1 and PDE10A2. The PDE10A19 transcript was detected in polysomal fractions; western blotting experiments confirmed that the RNA transcript is translated into protein. Immunocytochemistry studies using transfected mouse striatal and cortical neurons demonstrated that the PDE10A19 protein distributes to the cytosol, like PDE10A1, and unlike PDE10A2, which is associated with plasma membranes. Immunoprecipitation and immunocytochemical experiments revealed that the PDE10A19 isoform interacts physically with PDE10A2 and, when expressed at elevated levels, interferes with the plasma membrane localization of PDE10A2. These studies illustrate the complexity of PDE10A gene expression in the human brain and highlight the need to unravel the gene's complex and complete coding capabilities along with its transcriptional and translational regulation to guide the development of therapeutic agents that target the protein for the treatment of neuropsychiatric illness. PMID- 26905416 TI - One-step Multiplex Transgenesis via Sleeping Beauty Transposition in Cattle. AB - Genetically modified cattle are important for developing new biomedical models and for an improved understanding of the pathophysiology of zoonotic diseases. However, genome editing and genetic engineering based on somatic cell nuclear transfer suffer from a low overall efficiency. Here, we established a highly efficient one-step multiplex gene transfer system into the bovine genome. PMID- 26905415 TI - Oxidative stress, anti-oxidants and the cross-sectional and longitudinal association with depressive symptoms: results from the CARDIA study. AB - Depression may be accompanied by increased oxidative stress and decreased circulating anti-oxidants. This study examines the association between depressive symptoms, F2-isoprostanes and carotenoids in a US community sample. The study includes 3009 participants (mean age 40.3, 54.2% female) from CARDIA (Coronary Artery Risk Development in Young Adults). Cross-sectional analyses were performed on data from the year 15 examination (2000-2001) including subjects whose depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale (CES-D) and had measurements of plasma F2-isoprostanes (gas chromatography/mass spectrometry) or serum carotenoids (high-performance liquid chromatography). Carotenoids zeaxanthin/lutein, beta-cryptoxanthin, lycopene, alpha-carotene, beta-carotene were standardized and summed. Longitudinal analyses were conducted using the data from other examinations at 5-year intervals. Cross lagged analyses investigated whether CES-D predicted F2-isoprostanes or carotenoids at the following exam, and vice versa. Regression analyses were controlled for sociodemographics, health and lifestyle factors. F2-isoprostanes were higher in subjects with depressive symptoms (CES-D ? 16) after adjustment for sociodemographics (55.7 vs 52.0 pg ml(-1); Cohen's d = 0.14, P < 0.001). There was no difference in F2-isoprostanes after further adjustment for health and lifestyle factors. Carotenoids were lower in those with CES-D scores ? 16, even after adjustment for health and lifestyle factors (standardized sum 238.7 vs 244.0, Cohen's d = -0.16, P < 0.001). Longitudinal analyses confirmed that depression predicts subsequent F2-isoprostane and carotenoid levels. Neither F2 isoprostanes nor carotenoids predicted subsequent depression. In conclusion, depressive symptoms were cross-sectionally and longitudinally associated with increased F2-isoprostanes and decreased carotenoids. The association with F2 isoprostanes can largely be explained by lifestyle factors, but lower carotenoids were independently associated with depressive symptoms. PMID- 26905417 TI - Limitations of a Cardiac Risk (QRISK2) Calculator in Patients with High Density Lipoprotein (HDL). AB - INTRODUCTION: There is existing debate as to the relationship between blood concentration of HDL (high density lipoprotein) and cardiovascular outcomes. Patients with hyperalphalipoproteinaemia (HALP) have high HDL levels and this can be attributed to a variety of factors. AIM AND METHODS: This study aims for the first time to examine the HALP cohort and understand demographics, relationship with cardiovascular disease (CVD) risk and scoring with a cardiac risk calculator (QRISK 2 calculator). RESULTS: The study found 42 patients had a statistically significant difference (p = 0.001) between CVD risk estimated using actual measured HDL (Score 1) versus CVD risk calculated using standard population mean HDL values (Score 2). Furthermore, in the CVD event group (n = 6) a significant difference was also seen between Score 1 and Score 2 (p = 0.027). CONCLUSION: The study highlights issues with underestimation of CVD risk in this population and strongly advocates use of standard population mean values in assessment of CVD risk. PMID- 26905418 TI - Past agricultural land use and present-day fire regimes can interact to determine the nature of seed predation. AB - Historical agriculture and present-day fire regimes can have significant effects on contemporary ecosystems. Although past agricultural land use can lead to long term changes in plant communities, it remains unclear whether these persistent land-use legacies alter plant-consumer interactions, such as seed predation, and whether contemporary disturbance (e.g., fire) alters the effects of historical agriculture on these interactions. We conducted a study at 27 sites distributed across 80,300 ha in post-agricultural and non-agricultural longleaf pine woodlands with different degrees of fire frequency to test the hypothesis that past and present-day disturbances that alter plant communities can subsequently alter seed predation. We quantified seed removal by arthropods and rodents for Tephrosia virginiana and Vernonia angustifolia, species of conservation interest. We found that the effects of land-use history and fire frequency on seed removal were contingent on granivore guild and microhabitat characteristics. Tephrosia virginiana removal was greater in low fire frequency sites, due to greater seed removal by rodents. Although overall removal of V. angustifolia did not differ among habitats, rodents removed more seeds than arthropods at post-agricultural sites and non-agricultural sites with low fire frequencies, but not at non agricultural sites with high fire frequencies. Land-use history and fire frequency also affected the relationship between microhabitat characteristics and removal of V. angustifolia. Our results suggest that historical agriculture and present-day fire regimes may alter seed predation by shifting the impact of rodent and arthropod seed predators among habitats, with potential consequences for the establishment of rare plant species consumed by one or both predators. PMID- 26905419 TI - Schizo-Obsessive Disorder: A Brief Report of Neuroimaging Findings. AB - BACKGROUND: The term 'schizo-obsessive disorder' was coined to describe schizophrenia (SCZ) patients who are also affected by obsessive-compulsive symptoms (OCS) or also meet the criteria for obsessive-compulsive disorder (OCD). Several studies have investigated the clinical and epidemiological features of OCS/OCD in SCZ, but the neuroimaging literature is sparse. The aim of this brief report is to describe some of the most important neuroimaging findings regarding schizo-obsessive disorder. METHODS: A literature search of the PubMed electronic database was conducted up to July 25, 2015. Search terms included 'schizo obsessive' combined with the names of specific neuroimaging techniques. RESULTS: Neuroimaging studies suggest that there may be a specific pattern of neuroanatomic dysfunction in schizo-obsessive patients, but the number of studies is limited and conclusions are preliminary because reports are of an exploratory nature. CONCLUSIONS: Further neurobiological research is needed to definitely determine whether schizo-obsessive disorder might have unique neuroanatomical and functional alterations. PMID- 26905420 TI - Effects of Prenatal Environmental Exposures on the Development of Endometriosis in Female Offspring. AB - BACKGROUND: Endometriosis has many hypothesized etiologies. Known risk factors include genetic predisposition, uterine outflow abnormalities, and iatrogenic causes. Of increasing concern is prenatal environmental exposures. However, the findings of studies investigating the relationships between prenatal environmental exposures and the development of endometriosis have not always been conclusive, and therefore, the relationships are debatable. METHODS: This review presents a summary and analysis of the current studies that investigated the effects of prenatal environmental exposures on the development of endometriosis in female offspring. RESULTS: Prenatal exposure to estrogenic substances (such as ethinyl estradiol and diethylstilbestrol) and environmental toxins (such as 2,3,7,8-tetrachlorodibenzo-p-dioxin, polychlorinated biphenyls, and bisphenol A) may increase the incidence of endometriosis in female offspring. However, exposure to cigarette smoke may protect against the development of endometriosis in female offspring mainly because of its antiestrogenic effects. CONCLUSION: Certain prenatal environmental exposures might result in the development of endometriosis in female offspring. In addition to known environmental exposures that predispose the development of endometriosis in adulthood, such as dioxin and radiation exposure (animal models), prenatal exposures are of increasing concern. PMID- 26905421 TI - FMR1 CGG Repeats: Reference Levels and Race-Ethnic Variation in Women With Normal Fertility (Study of Women's Health Across the Nation). AB - FMR1 premutation carriers (55-199 CGG repeats), and potentially women with high normal (35-44) or low normal (<28) CGG repeats, are at risk of premature ovarian aging. The scarcity of population data on CGG repeats <45 CGG, and variation in race-ethnicity, makes it difficult to determine true associations. DNA was analyzed for FMR1 CGG repeat lengths from 803 women (386 caucasians, 219 African Americans, 102 Japanese, and 96 Chinese) from the US-based Study of Women's Health Across the Nation (SWAN). Participants had >=1 menses in the 3 months before enrollment, >=1 pregnancy, no history of infertility or hormonal therapy, and menopause >=46 years. Statistical analyses used Fisher exact tests. Among these women with normal reproductive histories, significant FMR1 repeat length differences were found across race-ethnicity for both the longer (P = .0002) and the shorter (P < .0001) alleles. The trinucleotide length variance was greater for non-Asian than Asian women (P < .0001), despite identical median values. Our data indicate that short allele lengths <25 CGG on one or both alleles are more common in non-Asian than Asian women. We confirm the minor allele in the 35 to 39 CGG range among Asians as reported previously. Only 2 (0.3%) premutation carriers were identified. These data demonstrate that FMR1 distributions do vary by race ethnicity, even within the "normal" range. This study indicates the need to control for race-ethnicity in FMR1 ovarian aging research and provides race ethnic population data for females separated by allele. PMID- 26905422 TI - Biomarkers of coronary endothelial health: correlation with invasive measures of collateral function, flow and resistance in chronically occluded coronary arteries and the effect of recanalization. AB - OBJECTIVES: In the presence of a chronically occluded coronary artery, the collateral circulation matures by a process of arteriogenesis; however, there is considerable variation between individuals in the functional capacity of that collateral network. This could be explained by differences in endothelial health and function. We aimed to examine the relationship between the functional extent of collateralization and levels of biomarkers that have been shown to relate to endothelial health. METHODS: We measured four potential biomarkers of endothelial health in 34 patients with mature collateral networks who underwent a successful percutaneous coronary intervention (PCI) for a chronic total coronary occlusion (CTO) before PCI and 6-8 weeks after PCI, and examined the relationship of biomarker levels with physiological measures of collateralization. RESULTS: We did not find a significant change in the systemic levels of sICAM-1, sE-selectin, microparticles or tissue factor 6-8 weeks after PCI. We did find an association between estimated retrograde collateral flow before CTO recanalization and lower levels of sICAM-1 (r=0.39, P=0.026), sE-selectin (r=0.48, P=0.005) and microparticles (r=0.38, P=0.03). CONCLUSION: Recanalization of a CTO and resultant regression of a mature collateral circulation do not alter systemic levels of sICAM-1, sE-selectin, microparticles or tissue factor. The identified relationship of retrograde collateral flow with sICAM-1, sE-selectin and microparticles is likely to represent an association with an ability to develop collaterals rather than their presence and extent. PMID- 26905423 TI - Whole-exome sequencing in individuals with multiple cardiovascular risk factors and normal coronary arteries. AB - OBJECTIVES: Most studies on the genes involved in coronary artery disease (CAD) targeted individuals with angiographically or clinically proven CAD. Focusing on high-risk individuals with normal coronary arteries (NCA) may offer novel insights into the pathogenesis of CAD. We aimed to identify genes putatively protective for development of CAD. METHODS: Pooled whole-exome sequencing (WES) was performed on 17 patients with multiple cardiovascular risk factors and NCA and on 17 controls with multivessel CAD. Rare NCA-unique sequence variants were subsequently individually validated using the Fluidigm platform in 100 additional CAD controls and 100 general population controls. RESULTS: In total, 555 100 variants were detected in at least one WES pool in the study group and in none of the control WES pools. For second phase validation, we focused on rare, nonsynonymous variants, resulting in a total of 144 variants in 40 genes, of which 96 were selected for subsequent genotyping. Validation phase genotyping resulted in 19 variants in 16 genes that were found in the NCA group and in none of the CAD controls. The SPTBN5, NID2, and ADAMTSL4 genes harbored sequence variants in more than one CAD-protected patient and none of the 117 CAD controls. CONCLUSION: Applying WES technology and focusing on individuals seemingly protected from developing CAD successfully identified 19 variants that may offer protection from CAD by undetermined mechanisms. Studying the genetics of high risk individuals apparently protected from CAD may provide novel insights into the pathogenesis of CAD. PMID- 26905424 TI - Mystery solved: Trehalose kickstarts autophagy by blocking glucose transport. AB - Although vertebrates cannot synthesize the natural disaccharide trehalose, exogenous administration of trehalose to mammalian cells may be beneficial for protein misfolding disorders. In this issue, DeBosch et al. show that trehalose may also be useful in treating nonalcoholic fatty liver disease and identify inhibition of cellular glucose import through SLC2A (also known as GLUT) transporters as a mechanism by which trehalose stimulates autophagy through the adenosine monophosphate-activated protein kinase (AMPK). PMID- 26905425 TI - Endothelial cells decode VEGF-mediated Ca2+ signaling patterns to produce distinct functional responses. AB - A single extracellular stimulus can promote diverse behaviors among isogenic cells by differentially regulated signaling networks. We examined Ca(2+) signaling in response to VEGF (vascular endothelial growth factor), a growth factor that can stimulate different behaviors in endothelial cells. We found that altering the amount of VEGF signaling in endothelial cells by stimulating them with different VEGF concentrations triggered distinct and mutually exclusive dynamic Ca(2+) signaling responses that correlated with different cellular behaviors. These behaviors were cell proliferation involving the transcription factor NFAT (nuclear factor of activated T cells) and cell migration involving MLCK (myosin light chain kinase). Further analysis suggested that this signal decoding was robust to the noisy nature of the signal input. Using probabilistic modeling, we captured both the stochastic and deterministic aspects of Ca(2+) signal decoding and accurately predicted cell responses in VEGF gradients, which we used to simulate different amounts of VEGF signaling. Ca(2+) signaling patterns associated with proliferation and migration were detected during angiogenesis in developing zebrafish. PMID- 26905426 TI - Trehalose inhibits solute carrier 2A (SLC2A) proteins to induce autophagy and prevent hepatic steatosis. AB - Trehalose is a naturally occurring disaccharide that has gained attention for its ability to induce cellular autophagy and mitigate diseases related to pathological protein aggregation. Despite decades of ubiquitous use as a nutraceutical, preservative, and humectant, its mechanism of action remains elusive. We showed that trehalose inhibited members of the SLC2A (also known as GLUT) family of glucose transporters. Trehalose-mediated inhibition of glucose transport induced AMPK (adenosine 5'-monophosphate-activated protein kinase) dependent autophagy and regression of hepatic steatosis in vivo and a reduction in the accumulation of lipid droplets in primary murine hepatocyte cultures. Our data indicated that trehalose triggers beneficial cellular autophagy by inhibiting glucose transport. PMID- 26905427 TI - Dynamic regulation of neutrophil polarity and migration by the heterotrimeric G protein subunits Galphai-GTP and Gbetagamma. AB - Activation of the Gi family of heterotrimeric guanine nucleotide-binding proteins (G proteins) releases betagamma subunits, which are the major transducers of chemotactic G protein-coupled receptor (GPCR)-dependent cell migration. The small molecule 12155 binds directly to Gbetagamma and activates Gbetagamma signaling without activating the Galphai subunit in the Gi heterotrimer. We used 12155 to examine the relative roles of Galphai and Gbetagamma activation in the migration of neutrophils on surfaces coated with the integrin ligand intercellular adhesion molecule-1 (ICAM-1). We found that 12155 suppressed basal migration by inhibiting the polarization of neutrophils and increasing their adhesion to ICAM-1-coated surfaces. GPCR-independent activation of endogenous Galphai and Gbetagamma with the mastoparan analog Mas7 resulted in normal migration. Furthermore, 12155 treated cells expressing a constitutively active form of Galphai1 became polarized and migrated. The extent and duration of signaling by the second messenger cyclic adenosine monophosphate (cAMP) were enhanced by 12155. Inhibiting the activity of cAMP-dependent protein kinase (PKA) restored the polarity of 12155-treated cells but did not decrease their adhesion to ICAM-1 and failed to restore migration. Together, these data provide evidence for a direct role of activated Galphai in promoting cell polarization through a cAMP-dependent mechanism and in inhibiting adhesion through a cAMP-independent mechanism. PMID- 26905428 TI - Tryptophan fluorescence quenching as a binding assay to monitor protein conformation changes in the membrane of intact mitochondria. AB - Intrinsic protein fluorescence is due to aromatic amino acids, mainly tryptophan, which can be selectively measured by exciting at 295 nm. Changes in emission spectra of tryptophan are due to the protein conformational transitions, subunit association, ligand binding or denaturation, which affect the local environment surrounding the indole ring. In this study, tryptophan fluorescence was monitored in intact mitochondria at 333 nm following excitation at 295 nm in presence of insecticides using spectrofluorometer. Methyl-parathion, carbofuran, and endosulfan induced Trp fluorescence quenching and release of cytochrome c when incubated with the mitochondria, except fenvalarate. Mechanism of insecticide induced mitochondrial toxicity for the tested insecticides has been discussed. Reduction in the intensity of tryptophan emission spectra of mitochondrial membrane proteins in presence of an increasing concentration of a ligand can be used to study the interaction of insecticides/drugs with the intact mitochondria. Furthermore, this assay can be readily adapted for studying protein-ligand interactions in intact mitochondria and in other cell organelles extending its implications for pesticide and pharma industry and in drug discovery. PMID- 26905429 TI - Sero-prevalence and associated risk factors for hepatitis C virus infection among voluntary counseling testing and anti retroviral treatment clinic attendants in Adwa hospital, northern Ethiopia. AB - BACKGROUND: Hepatitis C virus (HCV) is a major health concern where about 3% of the world's population is infected globally. In Ethiopia the prevalence ranges from 0.9 to 1.3% in the general populations. Human immune deficiency virus (HIV) patients due to their weak immune response are heavily affected by the virus. There is no data on magnitude and associated risk factors for HCV infection among voluntary counseling, testing center and anti retroviral treatment clinic Attendants in the study area. Therefore, the aim of this study was to determine the sero-prevalence and associated risk factors for HCV infection among voluntary counseling testing and anti retroviral treatment clinic attendants Adwa general hospital. METHODS: Cross sectional study was carried out among 302 participants (151 HIV-negative from VCT and 151 HIV-positive from ART follow up) clinics of Adwa hospital from September to December, 2014. About 5 ml of venous blood samples were collected from study participants for anti HCV antibody tests. Univariate analyses were used to identify associated variables with anti HCV positivity. Variables having p < 0.05 were considered as statistically significant association. RESULTS: Out of the total 302 participants, 52.6% of them were females and 47.4% males. The mean age of the participants was 34.1 year (SD +/- 10.5). The overall sero-prevalence of HCV in this study was 4.3%. The prevalence HCV (6.6%) was higher among the ART clinic attendants than the VCT (2%) clinic attendants. History of hospitalization (p = 0.001), tooth extraction (p = 0.018) and blood transfusion (p = 0.041) showed statistically significant association with anti-HCV antibody. CONCLUSION: HCV sero-prevalence in this study was high. The prevalence was three fold higher among HIV positive patients than their counter parts. Thus, screening of HCV should be done among HIV patients for close monitoring and better management in HIV patients. PMID- 26905430 TI - The foundation layer of quantitative cardiac PET/MRI: Attenuation correction. Again. PMID- 26905431 TI - Human Secreted Ly-6/uPAR Related Protein-1 (SLURP-1) Is a Selective Allosteric Antagonist of alpha7 Nicotinic Acetylcholine Receptor. AB - SLURP-1 is a secreted toxin-like Ly-6/uPAR protein found in epithelium, sensory neurons and immune cells. Point mutations in the slurp-1 gene cause the autosomal inflammation skin disease Mal de Meleda. SLURP-1 is considered an autocrine/paracrine hormone that regulates growth and differentiation of keratinocytes and controls inflammation and malignant cell transformation. The majority of previous studies of SLURP-1 have been made using fusion constructs containing, in addition to the native protein, extra polypeptide sequences. Here we describe the activity and pharmacological profile of a recombinant analogue of human SLURP-1 (rSLURP-1) differing from the native protein only by one additional N-terminal Met residue. rSLURP-1 significantly inhibited proliferation (up to ~ 40%, EC50 ~ 4 nM) of human oral keratinocytes (Het-1A cells). Application of mecamylamine and atropine,--non-selective inhibitors of nicotinic acetylcholine receptors (nAChRs) and muscarinic acetylcholine receptors, respectively, and anti alpha7-nAChRs antibodies revealed alpha7 type nAChRs as an rSLURP-1 target in keratinocytes. Using affinity purification from human cortical extracts, we confirmed that rSLURP-1 binds selectively to the alpha7-nAChRs. Exposure of Xenopus oocytes expressing alpha7-nAChRs to rSLURP-1 caused a significant non competitive inhibition of the response to acetylcholine (up to ~ 70%, IC50 ~ 1 MUM). It was shown that rSLURP-1 binds to alpha7-nAChRs overexpressed in GH4Cl cells, but does not compete with 125I-alpha-bungarotoxin for binding to the receptor. These findings imply an allosteric antagonist-like mode of SLURP-1 interaction with alpha7-nAChRs outside the classical ligand-binding site. Contrary to rSLURP-1, other inhibitors of alpha7-nAChRs (mecamylamine, alpha bungarotoxin and Lynx1) did not suppress the proliferation of keratinocytes. Moreover, the co-application of alpha-bungarotoxin with rSLURP-1 did not influence antiproliferative activity of the latter. This supports the hypothesis that the antiproliferative activity of SLURP-1 is related to 'metabotropic' signaling pathway through alpha7-nAChR, that activates intracellular signaling cascades without opening the receptor channel. PMID- 26905432 TI - Differences in the Pulsatile Component of the Skin Hemodynamic Response to Verbal Fluency Tasks in the Forehead and the Fingertip. AB - Several studies have claimed that hemodynamic signals measured by near-infrared spectroscopy (NIRS) on the forehead exhibit different patterns during a verbal fluency task (VFT) in various psychiatric disorders, whereas many studies have noted that NIRS signals can reflect task-related changes in skin blood flow. If such a task-related skin hemodynamic response is also observed in the fingertip, a simpler biomarker may be developed. Furthermore, determining the difference in the response pattern may provide physiological insights into the condition. We found that the magnitude of the pulsatile component in skin hemodynamic signals increased on the forehead (p < 0.001 for N = 50, p = 0.073 for N = 8) but decreased on the fingertip (p < 0.001, N = 8) during the VFT, whereas the rate in both areas increased (p < 0.02, N = 8). We also did not find a repetition effect in both the rate and the magnitude on the fingertip, whereas the effect was present in the magnitude (p < 0.02, N = 8) but not in the rate on the forehead. These results suggest that the skin vasomotor system in the forehead could have a different vessel mechanism to psychological tasks compared to the fingertip. PMID- 26905433 TI - The Study of Low Calcium Dialysate on Elderly Hemodialysis Patients with Secondary Hypoparathyroidism. AB - OBJECTIVE: The study aimed to study the safety and efficacy of 1.25 mmol/l calcium dialysate on maintenance hemodialysis (MHD) in elderly patients who suffered from secondary hypoparathyroidism. METHODS: Eighty-two elderly patients (ages >=65) who had been in MHD with dialysate calcium at 1.5 mmol/l over 6 months and had 2 consecutive serum intact parathyroid hormone (iPTH) measurements at level below 100 pg/ml were selected and randomized into 2 groups: treatment group (41 patients, with dialysate calcium at 1.25 mmol/l) and control group (41 patients, still with dialysate calcium at 1.5 mmol/l). Both groups were studied for the duration of 12 months. The changes of serum iPTH, calcium, phosphorus, calcium and phosphorus product and other indicators as well as related adverse reactions were recorded at the following time points: before the study and 1, 3, 6 and 12 months into the study. In addition, the intimal media thickness (IMT) of carotid artery and abdominal aorta calcification score (AACS) were measured in the 0, 6 and 12 months during the study. RESULTS: (1) In the treatment group, the levels of serum corrected calcium, phosphorus and calcium-phosphate product began to decline after 1 month and exhibited further decrease 3 months later. Serum iPTH level increased significantly after 1 month into the study and the trend continued. The above markers stabilized after month 6. Compared with pre-study markers, the changes of the above markers were significant after study (p < 0.05). (2) The average IMT and AACS were evidently decreased during the 6 and 12 months of study in the treatment group. There was statistical significance (p < 0.05) when compared with the above indexes of the pre-study and the control group. (3) In the control group, there were no significant differences in above laboratory markers over the 12-month study period. (4) There was no significant difference in the adverse events observed between the 2 groups. CONCLUSION: Safety of low calcium dialysate (dialysate calcium 1.25 mmol/l) in elderly MHD patients with iPTH <100 pg/ml is good, as well as improving carotid IMT, resistance index and AACS as indexes of vascular calcification in the small study group and warrants further investigation. PMID- 26905434 TI - Late side effects of robotic surgery. PMID- 26905435 TI - Report on NRG Oncology and the GOG Foundation. PMID- 26905436 TI - Uroprotective effect of oleuropein in a rat model of hemorrhagic cystitis. AB - Hemorrhagic cystitis is one of the devastating complications seen after receiving cyclophosphamide chemotherapy. Oleuropein is the most important phenolic compound of olive leaves that mediates most of its beneficial pharmacological properties. Herein, we investigated the possible uroprotective effect of oleuropein against cyclophosphamide induced hemorrhagic cystitis in a rat model. For this purpose, we measured bladder nitric oxide, reduced glutathione, catalase, tumor necrosis factor-alpha and vascular endothelial growth factor levels in addition to the bladder gene expression of intercellular adhesion molecule-1 after induction of hemorrhagic cystitis in the presence or absence of oleuropein. Histopathological examination of bladder tissues was also performed. After cyclophosphamide injection, we demonstrated a significant decrease in bladder reduced glutathione (39%) and catalase (55.4%) levels and a significant increase of nitric oxide (5.6 folds), tumor necrosis factor-alpha (3.3 folds), vascular endothelial growth factor (2 folds) and intercellular adhesion molecule-1 (8 folds) bladder contents when compared to those in normal control rats. Administration of oleuropein induced a marked elevation in bladder reduced glutathione (37.8%), catalase (100.4%) with a prominent reduction of bladder nitric oxide (40%), tumor necrosis factor-alpha (35.9%) and vascular endothelial growth factor (56.2%) levels along with downregulation of intercellular adhesion molecule-1 bladder expression (73.1%) in comparison to cyclophosphamide treated rats levels. Our data demonstrated that oleuropein counteracts the harmful effects of cyclophosphamide on the bladder through its antioxidant and anti-inflammatory activities. Oleuropein exerts a definite uroprotective effect against cyclophosphamide induced hemorrhagic cystitis in rats. PMID- 26905437 TI - Surface proteome analysis identifies platelet derived growth factor receptor alpha as a critical mediator of transforming growth factor-beta-induced collagen secretion. AB - Fibroblasts are extracellular matrix-producing cells in the lung. Fibroblast activation by transforming growth factor-beta leads to myofibroblast differentiation and increased extracellular matrix deposition, a hallmark of pulmonary fibrosis. While fibroblast function with respect to migration, invasion, and extracellular matrix deposition has been well-explored, little is known about the surface proteome of lung fibroblasts in general and its specific response to fibrogenic growth factors, in particular transforming growth factor beta. We thus performed a cell-surface proteome analysis of primary human lung fibroblasts in presence/absence of transforming growth factor-beta, followed by characterization of our findings using FACS analysis, Western blot, and siRNA mediated knockdown experiments. We identified 213 surface proteins significantly regulated by transforming growth factor-beta, platelet derived growth factor receptor-alpha being one of the top down-regulated proteins. Transforming growth factor beta-induced downregulation of platelet derived growth factor receptor alpha induced upregulation of platelet derived growth factor receptor-beta expression and phosphorylation of Akt, a downstream target of platelet derived growth factor signaling. Importantly, collagen type V expression and secretion was strongly increased after forced knockdown of platelet derived growth factor receptor-alpha, an effect that was potentiated by transforming growth factor beta. We therefore show previously underappreciated cross-talk of transforming growth factor-beta and platelet derived growth factor signaling in human lung fibroblasts, resulting in increased extracellular matrix deposition in a platelet derived growth factor receptor-alpha dependent manner. These findings are of particular importance for the treatment of lung fibrosis patients with high pulmonary transforming growth factor-beta activity. PMID- 26905438 TI - Minimally Invasive but Maximally Obstructive: Carcinoma In Situ Obstructing a Mainstem Bronchus. AB - Here we report a case of mainstem bronchus obstruction due to a carcinoma in situ. Preinvasive lesions, such as carcinoma in situ, are usually small and limited to the bronchial wall. This exceptional presentation shows a tumor growth large enough to completely occlude the right mainstem bronchus. The endoluminal lesion was removed using rigid bronchoscopy. The patient, not eligible for a local treatment, has been treated with surgery. PMID- 26905440 TI - Negative EBUS-TBNA Predicts Very Low Prevalence of Mediastinal Disease in Staging of Non-Small Cell Lung Cancer. AB - BACKGROUND: Confirmation of mediastinal disease (N2/3) in non-small cell lung cancer (NSCLC) generally precludes curative surgical management. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has become a routine first test in mediastinal staging of NSCLC; however, it remains unclear whether a negative EBUS-TBNA should be followed by mediastinoscopy before proceeding to surgery. Understanding the prevalence of metastases in lymph nodes with benign findings on EBUS-TBNA will inform decision making following negative EBUS-TBNA. METHODS: We examined a retrospective cohort of patients who underwent EBUS-TBNA before resection with mediastinal lymph node sampling for NSCLC between December 2009 and June 2014 in 3 hospitals in Melbourne, Australia. All patients had integrated positron emission tomography/computed tomography (PET/CT) before EBUS-TBNA. RESULTS: Eighty-two matched mediastinal lymph node stations were sampled in 57 patients by both EBUS-TBNA and surgical resection, 47 nodes in patients staged cN0/1 by PET/CT and 35 nodes in patients staged cN2/3. All patients had a negative EBUS-TBNA. Four malignant nodes were identified surgically (4.9% of lymph nodes). The mean size of malignant deposits was 5.5 mm. Per-node negative predictive value was 78/82=0.95. All malignant nodes were located in patients with moderate-high risk disease (cN2/3), giving a disease prevalence in cN2/3 patients of 11%, and 0% in cN0/1. In patients staged cN2, per node NVP was 0.89. CONCLUSION: The prevalence of mediastinal nodal disease following negative EBUS-TBNA is very low, at 4.9%. The per-node NVP of EBUS-TBNA is 0.95, decreasing to 0.89 in moderate-high risk patients. We suggest that a negative EBUS-TBNA of mediastinal nodes does not need to be confirmed by mediastinoscopy of those nodal stations, regardless of PET/CT findings. PMID- 26905441 TI - Endobronchial Ultrasound-guided Aspiration of an Endotracheal Bronchogenic Cyst: Case Report and Systematic Review of the Literature. AB - The most common location of bronchogenic cysts is the mediastinum, adjacent to the major airways. Endotracheal bronchogenic cysts are rare and most present in infancy with respiratory failure. Although surgical resection has remained the treatment of choice, there is increasing interest in the management of these cysts with therapeutic aspiration alone. In this article, we describe a 68-year old man with endotracheal bronchogenic cyst who was managed with endobronchial ultrasound-guided needle aspiration. We also systematically review the literature for reports of endotracheal bronchogenic cysts. The review identified 9 reports (10 patients) with endotracheal bronchogenic cysts. The most common age at presentation was infancy (n=8) and surgical resection was the most common treatment modality used (n=7). PMID- 26905442 TI - Use of Indwelling Pleural Catheter for Recurrent Pleural Effusion Due to Postpericardiotomy Syndrome: A Case Report. AB - Pleural effusion secondary to postpericardiotomy syndrome (PPS) is a relatively common complication after cardiac surgery. These effusions and syndrome complex usually respond well to anti-inflammatory agents. The use of indwelling pleural catheter (IPC) for nonmalignant recurrent pleural effusions is growing. We report the use of IPC for a case of recurrent pleural effusion due to PPS in a gentleman that could not tolerate anti-inflammatory medications. To our knowledge, there has been no other report of the use of IPC due to recurrent pleural effusion from PPS. PMID- 26905443 TI - How Long Is Too Long? Trials and Tribulations of an Indolent Tumor. AB - A 31-year-old African American man presented for workup of a right hilar and tracheal mass. Stability of the mass when compared with a computed tomographic scan performed 3 years prior suggested an indolent process. On bronchoscopy, there were 2 separate although morphologically similar endobronchial lesions, one in the distal trachea and the second at the level of the right upper lobe bronchus. Biopsies of both lesions demonstrated granular cell tumors. Subsequent rigid bronchoscopy with ablation led to resolution of wheeze, decrease in dyspnea, and documented improvements in both ventilation and perfusion to the right lung. This case illustrates both a rare disease (multifocal endobronchial granular cell tumor) and the physiological impact of reducing large airway obstruction. PMID- 26905445 TI - Editorial. PMID- 26905444 TI - Elastic, magnetic and electronic properties of iridium phosphide Ir2P. AB - Cubic (space group: Fmm) iridium phosphide, Ir2P, has been synthesized at high pressure and high temperature. Angle-dispersive synchrotron X-ray diffraction measurements on Ir2P powder using a diamond-anvil cell at room temperature and high pressures (up to 40.6 GPa) yielded a bulk modulus of B0 = 306(6) GPa and its pressure derivative B0' = 6.4(5). Such a high bulk modulus attributed to the short and strongly covalent Ir-P bonds as revealed by first - principles calculations and three-dimensionally distributed [IrP4] tetrahedron network. Indentation testing on a well-sintered polycrystalline sample yielded the hardness of 11.8(4) GPa. Relatively low shear modulus of ~64 GPa from theoretical calculations suggests a complicated overall bonding in Ir2P with metallic, ionic, and covalent characteristics. In addition, a spin glass behavior is indicated by magnetic susceptibility measurements. PMID- 26905446 TI - Climate, soil texture, and soil types affect the contributions of fine-fraction stabilized carbon to total soil organic carbon in different land uses across China. AB - Mineral-associated organic carbon (MOC), that is stabilized by fine soil particles (i.e., silt plus clay, <53 MUm), is important for soil organic carbon (SOC) persistence and sequestration, due to its large contribution to total SOC (TSOC) and long turnover time. Our objectives were to investigate how climate, soil type, soil texture, and agricultural managements affect MOC contributions to TSOC in China. We created a dataset from 103 published papers, including 1106 data points pairing MOC and TSOC across three major land use types: cropland, grassland, and forest. Overall, the MOC/TSOC ratio ranged from 0.27 to 0.80 and varied significantly among soil groups in cropland, grassland, and forest. Croplands and forest exhibited significantly higher median MOC/TSOC ratios than in grassland. Moreover, forest and grassland soils in temperate regions had higher MOC/TSOC ratios than in subtropical regions. Furthermore, the MOC/TSOC ratio was much higher in ultisol, compared with the other soil types. Both the MOC content and MOC/TSOC ratio were positively correlated with the amount of fine fraction (silt plus clay) in soil, highlighting the importance of soil texture in stabilizing organic carbon across various climate zones. In cropland, different fertilization practices and land uses (e.g., upland, paddy, and upland-paddy rotation) significantly altered MOC/TSOC ratios, but not in cropping systems (e.g., mono- and double-cropping) characterized by climatic differences. This study demonstrates that the MOC/TSOC ratio is mainly driven by soil texture, soil types, and related climate and land uses, and thus the variations in MOC/TSOC ratios should be taken into account when quantitatively estimating soil C sequestration potential of silt plus clay particles on a large scale. PMID- 26905447 TI - The impact and efficacy of routine pulse oximetry screening for CHD in a local hospital. AB - OBJECTIVES: The objective of this study was to evaluate the impact and efficacy of pulse oximetry screening for CHD in a level-two neonatal unit without on-site access to paediatric echocardiography. METHODS: All neonatal unit admissions between 1 September, 2011 and 31 August, 2013 were reviewed to determine the outcomes of newborns identified by pulse oximetry screening. Record linkage with the National Congenital Heart Disease Audit allowed follow-up of newborns with a negative screening result. RESULTS: There were 11,233 live births during the study period, with 973 neonatal unit admissions unrelated to pulse oximetry screening. From the remaining screening population of 10,260 newborns, 23 were admitted on the basis of a screen-positive result; three of the 23 patients went on to have urgent echocardiograms, and two were found to have critical CHD. In the 21 newborns without critical CHD, an alternative diagnosis was made in 16 cases. Record linkage with the National Congenital Heart Disease Audit indicated that no newborns born in the hospital during the study period received surgery for critical CHD following negative screening. The estimated sensitivity of screening was 100% (95% confidence interval 15.81-100%) and specificity was 99.80% (95% confidence interval 99.69-99.87%), with a false-positive rate of 0.20% (95% confidence interval 0.13-0.31%). CONCLUSION: The introduction of pulse oximetry screening to a hospital where paediatric echocardiography services are not available is practical, results in very few referrals to the regional paediatric cardiology centre, and detects cases of CHD that would otherwise go undiagnosed. Record linkage with a national CHD database provides a straightforward method for tracking cases of CHD that may have been missed by screening. PMID- 26905450 TI - Corticosterone levels and behavioral changes induced by simultaneous exposure to chronic social stress and enriched environments in NMRI male mice. AB - Environmental enrichment (EE) is an experimental model which is believed to counteract some of the effects induced by stressors, although few studies have exposed rodents simultaneously to EE and stress. Our aim was to compare the short and long-term effects of different housing conditions in mice submitted to chronic stress. 128 NMRI male mice arrived at our laboratory on postnatal day (PND) 21. During Phase I (PND 28), animals were randomly assigned to four experimental conditions: 1) EE+STRESS: mice housed in EE and submitted to social stress (n=32); 2) EE+NO STRESS: mice housed in EE without stress (n=32); 3) SE+STRESS: mice maintained in standard conditions (SE) and submitted to social stress (n=32); and 4) SE+NO STRESS (n=32). At the end of Phase I (PND 77), one cohort of 32 animals was used for behavioral assessment whereas another cohort of 32 was sacrificed for corticosterone analysis. Results indicated that EE animals showed less body weight, higher water and food intake, diminished anxiety response and decreased motor and exploratory behavior than SE mice. Mice exposed to stress gained less body weight, showed higher food and fluid intake and displayed decreased exploratory behavior than non-stressed mice. Furthermore, EE+STRESS group displayed significantly higher corticosterone levels than EE+NO STRESS group whereas EE+NO STRESS group showed lower levels than SE+NO STRESS. On PND 83, Phase II of the study began. Animals (n=96) were assigned to two different housing conditions: EE (n=48) and SE (n=48). On PND 112, corticosterone analysis (n=32) and behavioral study (n=64) were done. The factor "Housing Phase II" reached statistical significance. Results indicated that EE animals showed lower body weight and higher fluid intake than SE group, as well as decreased anxiety. No clear effects on motor and exploratory behavior or learning were observed. When long-term effects were analyzed, results indicated that "Initial Housing" condition was significant: animals allocated in EE during Phase I of the study showed higher corticosterone levels, lower body weight and higher fluid intake than SE mice. "Initial Stress" had significant long-term actions on food intake and exploratory behavior: animals initially reared under stress conditions displayed higher food intake and lower exploration levels on the hole-board test than non-stressed mice. In the elevated plus-maze, there were significant interactions between factors "Initial Housing" and "Initial Stress". These factors did not reach statistical significance for motor activity or learning task. We can conclude that both short- and long-term effects of housing conditions are evident for corticosterone levels, body weight and fluid intake. Social stress induced short-term effects on body weight, food and fluid intake and exploratory behavior whereas long-acting effects were reflected on food intake and exploratory behavior. Further studies are needed in order to explore more in depth behavioral and physiological consequences of social stress and environmental enrichment. PMID- 26905451 TI - The Pavlovian craver: Neural and experiential correlates of single trial naturalistic food conditioning in humans. AB - Present-day environments are replete with tempting foods and the current obesity pandemic speaks to humans' inability to adjust to this. Pavlovian processes may be fundamental to such hedonic overeating. However, a lack of naturalistic Pavlovian paradigms in humans makes translational research difficult and important parameters such as implicitness and acquisition speed are unknown. Here we present a novel naturalistic conditioning task: an image of a neutral object was conditioned to marzipan taste in a single trial procedure by asking the participant to eat the 'object' (made from marzipan). Relative to control objects, results demonstrate robust pre- to post-conditioning changes of both subjective ratings and early as well as late event related brain potentials, suggesting contributions of implicit (attentional) and explicit (motivational) processes. Naturalistic single-trial taste-appetitive conditioning is potent in humans and shapes attentional and motivational neural processes that might challenge self-regulation during exposure to tempting foods. Thus, appetitive conditioning processes might contribute to overweight and obesity. PMID- 26905453 TI - Traumatic orbital encephalocele: Presentation and imaging. AB - OBJECTIVE: Traumatic orbital encephalocele is a rare but severe complication of orbital roof fractures. We describe 3 cases of orbital encephalocele due to trauma in children. METHODS: Retrospective case series from the University of Wisconsin - Madison and Medical College of Wisconsin. RESULTS: Three cases of traumatic orbital encephalocele in pediatric patients were found. The mechanism of injury was motor vehicle accident in 2 patients and accidental self-inflicted gunshot wound in 1 patient. All 3 patients sustained orbital roof fractures (4 mm to 19 mm in width) and frontal lobe contusions with high intracranial pressure. A key finding in all 3 cases was progression of proptosis and globe displacement 4 to 11 days after initial injury. On initial CT, all were diagnosed with extraconal hemorrhage adjacent to the roof fractures, with subsequent enlargement of the mass and eventual diagnosis of encephalocele. CONCLUSION: Orbital encephalocele is a severe and sight-threatening complication of orbital roof fractures. Post-traumatic orbital encephalocele can be challenging to diagnose on CT as patients with this condition often have associated orbital and intracranial hematoma, which can be difficult to distinguish from herniated brain tissue. When there is a high index of suspicion for encephalocele, an MRI of the orbits and brain with contrast should be obtained for additional characterization. Imaging signs that should raise suspicion for traumatic orbital encephalocele include an enlarging heterogeneous orbital mass in conjunction with a roof fracture and/or widening fracture segments. PMID- 26905452 TI - Pitfalls in the analysis of the physiological antioxidant glutathione (GSH) and its disulfide (GSSG) in biological samples: An elephant in the room. AB - Glutathione (GSH) is the most abundant low-molecular-mass thiol within cells and one of the major antioxidant compounds in body fluids. Under pro-oxidant conditions, two GSH molecules donate one electron each and are converted into glutathione disulfide (GSSG). The GSH/GSSG molar ratio is considered a powerful index of oxidative stress and disease risk. Despite high interest in GSH/GSSG titration as measures of thiol redox balance, no broad agreement has yet been reached as to the best pre-analytical and analytical methods for the quantitation of these molecules in biological samples. Consequently, measured concentrations of GSH and GSSG and calculated GSH/GSSG molar ratios vary widely among laboratories. Here, we describe in detail the main analytical and pre-analytical problems related to the artificial oxidation of the sulfhydryl (SH) group of GSH that occur during sample manipulation. We underline how this aspect has been neglected for long time after its first description more than fifty years ago. Finally, selected reliable procedures and methods to measure GSH and GSSG in biological samples are discussed. PMID- 26905454 TI - Outcomes Knowledge May Bias Radiological Decision-making. AB - RATIONALE AND OBJECTIVES: This research investigates whether an expectation of abnormality and prior knowledge might potentially influence the decision-making of radiologists, and discusses the implications for radiological expert witness testimony. MATERIALS AND METHODS: This study was a web-based perception experiment. A total of 12 board-certified radiologists were asked to interpret 40 adult chest images (20 abnormal) twice and decide if pulmonary lesions were present. Before the first viewing, a general clinical history was given for all images: cough for 3+ weeks. This was called the "defendants read." Two weeks later, the radiologists were asked to view the same dataset (unaware that the dataset was unchanged). For this reading, the radiologists were given the following information for all images: "These images were reported normal but all of these patients have a lung tumour diagnosed on a subsequent radiograph 6 months later." They were also given the lobar location of the newly diagnosed tumor. This was called the "expert witness read." RESULTS: There was a significant difference in location-based sensitivity (W = -45, P = 0.02) between the two conditions with nodule detection increasing under the second condition. Specificity increased outside the lobe of interest (W = 727, P = < 0.0001) and decreased within the lobe of interest (W = -237, P = 0.03) significantly in the "expert witness" read. Case-based sensitivity and case-based specificity were unaffected. CONCLUSIONS: This study showed evidence that increased clinical information affects the performance of radiologists. This effect may bias expert witnesses in radiological malpractice litigation. PMID- 26905455 TI - Systematic Comparison of Reduced Tube Current Protocols for High-pitch and Standard-pitch Pulmonary CT Angiography in a Large Single-center Population. AB - RATIONALE AND OBJECTIVES: Benefits of iterative reconstruction (IR) algorithms combined with dose-reduction techniques have been shown at computed tomography pulmonary angiography (CTPA) in several medium to small patient collectives. In this study, we performed a systematic comparison of image quality to combinations of reduced tube current (RC) and IR for both standard-pitch (SP) single-source and high-pitch (HP) dual-source CTPA in a large, single-center population. MATERIALS AND METHODS: Three hundred eighty-two consecutive patients (October 2010 through December 2012) received clinically indicated CTPA with one of four consecutively changed protocols: (1) HPSC: 180 mAs, weighted filtered back projection, pitch = 3; (2) HPRC: 90 mAs, IR, pitch = 3; (3) SPSC: 180 mAs, weighted filtered back projection, pitch = 1.2; and (4) HPRC: 90 mAs, IR, pitch = 1.2. Tube potential was 100 kV. Vascular attenuation and standardized signal-to noise ratio (sSNR) were measured in the pulmonary trunk (sSNRPT) and on segmental artery level (sSNRS1, sSNRS10). Dose-length-product was recorded per series. Two independent investigators rated image quality. Kolmogorov-Smirnov test, Kruskal Wallis test, and kappa statistics were used for statistical analysis. Median values are presented per group. RESULTS: Image quality was consistent between all groups (observer 1: P = 0.118; observer 2: P = 0.122). Inter-reader consistency was very good (kappa = 0.866, P < 0.001). Dose-length-product was significantly reduced in HP and RC groups (P < 0.001 for each; SPSC: 139.5 mGycm; HPRC: 92 mGycm; SPSC: 211 mGycm; HPRC: 137 mGycm). sSNR was comparable (sSNRPT overall: P = 0.052; sSNRS1 overall: P = 0.161; and sSNRS10 overall: P = 0.259). CONCLUSIONS: Substantial dose reduction can be within a routine clinical setting without quantifiable loss of image quality either by HP pulmonary angiography or by a combination of IR and RC in either HP or SP acquisition. PMID- 26905456 TI - Bridging the generation gap: Intergenerational service-learning benefits young and old. AB - Intergenerational service-learning is commonly used in aging courses. Although benefits are well documented for college students, fewer studies have examined benefits for older adults. This article discusses the development and implementation of an intergenerational program designed as a brief service learning experience to reduce age-related stereotypes and increase generativity in older adults. Young adults enrolled in an aging course and older adults from a local assisted-living community met three times to discuss a variety of topics and get to know one another. Results showed a significant reduction in ageism on the Fraboni Scale of Ageism for young adults. Descriptive data suggested an increase in generativity on the Loyola Generativity Scale for older adults. Qualitative data suggested that all participants gained a greater appreciation for one another and recognized how much they had in common. Limitations, challenges, and lessons learned are also discussed. Intergenerational service learning, even in small doses, shows promise for bridging the generation gap. PMID- 26905458 TI - Cardiovascular adaptations supporting human exercise-heat acclimation. AB - This review examines the cardiovascular adaptations along with total body water and plasma volume adjustments that occur in parallel with improved heat loss responses during exercise-heat acclimation. The cardiovascular system is well recognized as an important contributor to exercise-heat acclimation that acts to minimize physiological strain, reduce the risk of serious heat illness and better sustain exercise capacity. The upright posture adopted by humans during most physical activities and the large skin surface area contribute to the circulatory and blood pressure regulation challenge of simultaneously supporting skeletal muscle blood flow and dissipating heat via increased skin blood flow and sweat secretion during exercise-heat stress. Although it was traditionally held that cardiac output increased during exercise-heat stress to primarily support elevated skin blood flow requirements, recent evidence suggests that temperature sensitive mechanisms may also mediate an elevation in skeletal muscle blood flow. The cardiovascular adaptations supporting this challenge include an increase in total body water, plasma volume expansion, better sustainment and/or elevation of stroke volume, reduction in heart rate, improvement in ventricular filling and myocardial efficiency, and enhanced skin blood flow and sweating responses. The magnitude of these adaptations is variable and dependent on several factors such as exercise intensity, duration of exposure, frequency and total number of exposures, as well as the environmental conditions (i.e. dry or humid heat) in which acclimation occurs. PMID- 26905457 TI - Receptor-targeted liposome-peptide-siRNA nanoparticles represent an efficient delivery system for MRTF silencing in conjunctival fibrosis. AB - There is increasing evidence that the Myocardin-related transcription factor/Serum response factor (MRTF/SRF) pathway plays a key role in fibroblast activation and that knocking down MRTF can lead to reduced scarring and fibrosis. Here, we have developed a receptor-targeted liposome-peptide-siRNA nanoparticle as a non-viral delivery system for MRTF-B siRNA in conjunctival fibrosis. Using 50 nM siRNA, the MRTF-B gene was efficiently silenced by 76% and 72% with LYR and LER nanoparticles, respectively. The silencing efficiency was low when non targeting peptides or siRNA alone or liposome-siRNA alone were used. LYR and LER nanoparticles also showed higher silencing efficiency than PEGylated LYR-P and LER-P nanoparticles. The nanoparticles were not cytotoxic using different liposomes, targeting peptides, and 50 nM siRNA. Three-dimensional fibroblast populated collagen matrices were also used as a functional assay to measure contraction in vitro, and showed that MRTF-B LYR nanoparticles completely blocked matrix contraction after a single transfection treatment. In conclusion, this is the first study to develop and show that receptor-targeted liposome-peptide-siRNA nanoparticles represent an efficient and safe non-viral siRNA delivery system that could be used to prevent fibrosis after glaucoma filtration surgery and other contractile scarring conditions in the eye. PMID- 26905459 TI - Central control of visceral pain and urinary tract function. AB - Afferent input from Adelta and C-fibres innervating the urinary bladder are processed differently by the brain, and have different roles in signaling bladder sensation. Adelta fibres that signal bladder filling activate a spino-bulbo spinal loop, which relays in the midbrain periaqueductal grey (PAG) and pontine micturition centre (PMC). The excitability of this circuitry is regulated by tonic GABAergic inhibitory processes. In humans and socialised animals micturition is normally under volitional control and influenced by a host of psychosocial factors. Higher nervous decision-making in a social context to 'go now' or 'do not go' probably resides in frontal cortical areas, which act as a central control switch for micturition. Exposure to psychosocial stress can have profoundly disruptive influence on the process and lead to maladaptive changes in the bladder. During sleeping the voiding reflex threshold appears to be reset to a higher level to promote urinary continence. Under physiological conditions C fibre bladder afferents are normally silent but are activated in inflammatory bladder states and by intense distending pressure. Following prolonged stimulation visceral nociceptors sensitise, leading to a lowered threshold and heightened sensitivity. In addition, sensitization may occur within the central pain processing circuitry, which outlasts the original nociceptive insult. Visceral nociception may also be influenced by genetic and environmental influences. A period of chronic stress can produce increased sensitivity to visceral pain that lasts for months. Adverse early life events can produce even longer lasting epigenetic changes, which increase the individual's susceptibility to developing visceral pain states in adulthood. PMID- 26905460 TI - Competition between Hexagonal and Tetragonal Hexabromobenzene Packing on Au(111). AB - Low-temperature scanning tunneling microscope investigations reveal that hexabromobenzene (HBB) molecules arrange in either hexagonally closely packed (hcp) [Formula: see text] or tetragonal [Formula: see text] structure on Au(111) dependent on a small substrate temperature difference around 300 K. The underlying mechanism is investigated by density functional theory calculations, which reveal that substrate-mediated intermolecular noncovalent C-Br...Br-C attractions induce hcp HBB islands, keeping the well-known Au(111)-22*?3 reconstruction intact. Upon deposition at 330 K, HBB molecules trap freely diffusing Au adatoms to form tetragonal islands. This enhances the attraction between HBB and Au(111) but partially reduces the intermolecular C-Br...Br-C attractions, altering the Au(111)-22*?3 reconstruction. In both cases, the HBB molecule adsorbs on a bridge site, forming a ~15 degrees angle between the C-Br direction and [112]Au, indicating the site-specific molecule-substrate interactions. We show that the competition between intermolecular and molecule substrate interactions determines molecule packing at the subnanometer scale, which will be helpful for crystal engineering, functional materials, and organic electronics. PMID- 26905461 TI - Standard Information Models for Representing Adverse Sensitivity Information in Clinical Documents. AB - BACKGROUND: Adverse sensitivity (e.g., allergy and intolerance) information is a critical component of any electronic health record system. While several standards exist for structured entry of adverse sensitivity information, many clinicians record this data as free text. OBJECTIVES: This study aimed to 1) identify and compare the existing common adverse sensitivity information models, and 2) to evaluate the coverage of the adverse sensitivity information models for representing allergy information on a subset of inpatient and outpatient adverse sensitivity clinical notes. METHODS: We compared four common adverse sensitivity information models: Health Level 7 Allergy and Intolerance Domain Analysis Model, HL7-DAM; the Fast Healthcare Interoperability Resources, FHIR; the Consolidated Continuity of Care Document, C-CDA; and OpenEHR, and evaluated their coverage on a corpus of inpatient and outpatient notes (n = 120). RESULTS: We found that allergy specialists' notes had the highest frequency of adverse sensitivity attributes per note, whereas emergency department notes had the fewest attributes. Overall, the models had many similarities in the central attributes which covered between 75% and 95% of adverse sensitivity information contained within the notes. However, representations of some attributes (especially the value-sets) were not well aligned between the models, which is likely to present an obstacle for achieving data interoperability. Also, adverse sensitivity exceptions were not well represented among the information models. CONCLUSIONS: Although we found that common adverse sensitivity models cover a significant portion of relevant information in the clinical notes, our results highlight areas needed to be reconciled between the standards for data interoperability. PMID- 26905462 TI - Influence of landscape features on the microgeographic genetic structure of a resident songbird. AB - Landscape features influence individual dispersal and as a result can affect both gene flow and genetic variation within and between populations. The landscape of British Columbia, Canada, is already highly heterogeneous because of natural ecological and geological transitions, but disturbance from human-mediated processes has further fragmented continuous habitat, particularly in the central plateau region. In this study, we evaluated the effects of landscape heterogeneity on the genetic structure of a common resident songbird, the black capped chickadee (Poecile atricapillus). Previous work revealed significant population structuring in British Columbia that could not be explained by physical barriers, so our aim was to assess the pattern of genetic structure at a microgeographic scale and determine the effect of different landscape features on genetic differentiation. A total of 399 individuals from 15 populations were genotyped for fourteen microsatellite loci revealing significant population structuring in this species. Individual- and population-based analyses revealed as many as nine genetic clusters with isolation in the north, the central plateau and the south. Moreover, a mixed modelling approach that accounted for non independence of pairwise distance values revealed a significant effect of land cover and elevation resistance on genetic differentiation. These results suggest that barriers in the landscape influence dispersal which has led to the unexpectedly high levels of population isolation. Our study demonstrates the importance of incorporating landscape features when interpreting patterns of population differentiation. Despite taking a microgeographic approach, our results have opened up additional questions concerning the processes influencing dispersal and gene flow at the local scale. PMID- 26905463 TI - Maize diversity associated with social origin and environmental variation in Southern Mexico. AB - While prevailing theories of crop evolution suggest that crop diversity and cultural diversity should be linked, empirical evidence for such a link remains inconclusive. In particular, few studies have investigated such patterns on a local scale. Here, we address this issue by examining the determinants of maize diversity in a local region of high cultural and biological richness in Southern Mexico. We collected maize samples from villages at low and middle elevations in two adjacent municipalities of differing ethnicity: Mixtec or Chatino. Although morphological traits show few patterns of population structure, we see clear genetic differentiation among villages, with municipality explaining a larger proportion of the differentiation than altitude. Consistent with an important role of social origin in patterning seed exchange, metapopulation model-based estimates of differentiation match the genetic data within village and ethnically distinct municipalities, but underestimate differentiation when all four villages are taken together. Our research provides insights about the importance of social origin in structuring maize diversity at the local scale. PMID- 26905464 TI - The effects of quantitative fecundity in the haploid stage on reproductive success and diploid fitness in the aquatic peat moss Sphagnum macrophyllum. AB - A major question in evolutionary biology is how mating patterns affect the fitness of offspring. However, in animals and seed plants it is virtually impossible to investigate the effects of specific gamete genotypes. In bryophytes, haploid gametophytes grow via clonal propagation and produce millions of genetically identical gametes throughout a population. The main goal of this research was to test whether gamete identity has an effect on the fitness of their diploid offspring in a population of the aquatic peat moss Sphagnum macrophyllum. We observed a heavily male-biased sex ratio in gametophyte plants (ramets) and in multilocus microsatellite genotypes (genets). There was a steeper relationship between mating success (number of different haploid mates) and fecundity (number of diploid offspring) for male genets compared with female genets. At the sporophyte level, we observed a weak effect of inbreeding on offspring fitness, but no effect of brood size (number of sporophytes per maternal ramet). Instead, the identities of the haploid male and haploid female parents were significant contributors to variance in fitness of sporophyte offspring in the population. Our results suggest that intrasexual gametophyte/gamete competition may play a role in determining mating success in this population. PMID- 26905465 TI - Characterization of cationic starch flocculants synthesized by dry process with ball milling activating method. AB - The cationic starch flocculants were synthesized by the reaction of maize starch which was activated by a ball-milling treatment with 2,3-epoxypropyl trimethyl ammonium chlorides (ETMAC) using the dry method. The cationic starches were characterized by several approaches including scanning electron microscope (SEM), degree of substitution (DS), infrared spectrum (IR), X-ray diffraction (XRD), flocculating activity, electron spin resonance (ESR), and solid-state nuclear magnetic resonance (NMR). The effect of mechanical activation on starch etherifying modification was investigated. The mechanical activation cracked starch granules and destructed their crystal structures. This resulted in enhancements to the reaction activity and reaction efficiency, which was approved by ESR and solid state NMR. The starch flocculants, synthesized by the reaction of mechanically activated starches at 90 degrees C for 2.5h with ETMAC at molar ratio of 0.40:1.00, showed good flocculation activity. The substitution degree (0.300) and reaction efficiency (75.06%) of starch flocculants synthesized with mechanically activated starches were significantly greater than those of starch flocculants with native starches (P<0.05). PMID- 26905466 TI - Crystallographic studies of the complex of human HINT1 protein with a non hydrolyzable analog of Ap4A. AB - Histidine triad nucleotide-binding protein 1 (HINT1) represents the most ancient and widespread branch in the histidine triad proteins superfamily. HINT1 plays an important role in various biological processes, and it has been found in many species. Here, we report the first structure (at a 2.34A resolution) of a complex of human HINT1 with a non-hydrolyzable analog of an Ap4A dinucleotide, containing bis-phosphorothioated glycerol mimicking a polyphosphate chain, obtained from a primitive monoclinic space group P21 crystal. In addition, the apo form of hHINT1 at the space group P21 refined to 1.92A is reported for comparative studies. PMID- 26905467 TI - A novel electrospinning approach to fabricate high strength aqueous silk fibroin nanofibers. AB - The present paper describes a rapid method of producing concentrated aqueous regenerated Bombyx mori silk fibroin (RSF) solution by applying mild shearing under forced dehumidified air and generation of electrospun SF nanofibers from concentrated solution with high mechanical strength using free liquid surface electrospinning machine. The shear induced concentrating mechanism favoured the electrospinning process by enhancing the viscosity (>2.43Pas as onset for electrospinning) and decreasing the surface tension of the solution (40.1 37.7mN/m). Shearing reduced the beta-turns and random coil molecular conformation and thereby, intensified the beta-sheet content from 16.9% to 34% which is the minimum content needed to commence RSF nanofibers formation. Subsequently, electrospun nanofibrous mats were produced from different batches of concentrated SF solutions (15-21wt%). Among the concentrated RSF, 17wt% RSF solution was the most favourable concentration producing electrospun nanofibrous mat having lowest average fiber diameters of 183+/-55nm and good tensile strength. The mechanical strength of the nanofibrous sheet was further improved by cross-linking with 1 ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride and N hydroxysuccinimide (EDC+NHS) which might be due to enhancement of beta-sheet content. These nanofibers exhibited 17.57+/-1.13MPa ultimate tensile strength, 12.48+/-1.46% tensile strain at break and 37.7% increase in root mean square surface roughness which is favourable feature for cell adhesion and neo-tissue formation. PMID- 26905468 TI - A bio-mimetic zinc/tau protein as an artificial catalase. AB - In this study, the catalase-like activity of monomeric tau protein was reported in the presence of of zinc (Zn(II)) ions at low pH value. Monomeric tau protein contains two SH groups that are a target of disulfide bond formation. However these SH groups are able to interact with Zn(II) ion at pH 7.2 which creates a thiol bond as a mimetic model of chloroperoxidase active site which performs catalase like activity at low pH. Zn(II)/tau protein complex decomposed H2O2 with a high rate (Vm) as well as an efficient turn oven number (kcat) at pH 3. This remarkable catalase like activity is may be attributed to the conformational reorientation of protein at low pH. Circular dichroism (CD) studies did not demonstrate any secondary structural changes of tau protein after addition of Zn(II) ions at pH 7.2. In addition, tau protein shows identical CD bands at pH 7.2 and 3. Moreover, fluorescence quenching of tau by Zn(II) at pH 7.2 was initiated by complex formation rather than by dynamic collision. A significant red shift (6nm) was observed in the emission maximum of the fluorescence spectra when the protein was dissolved at pH 3 compared to pH 7.2. This conformational change can provide information regarding the rearrangements of the protein structure and exposure of Cys-Zn(II) group to the solvent which induces easy access of active site to H2O2 molecules and corresponding enhanced catalytic activity of Zn(II)/tau protein complex. This study introduces tau protein as a bio-inspired high performing scaffold for transition metal encapsulation and introducing an engineered apoprotein-induced biomimetic enzyme. PMID- 26905469 TI - Antenatal corticosteroid administration before elective caesarean section at term to prevent neonatal respiratory morbidity: a randomized controlled trial. AB - OBJECTIVE: To assess the effect of prophylactic corticosteroid administration before elective caesarean section at term (between 38 and 38(+6) weeks) in reducing neonatal respiratory morbidity and admission to a neonatal intensive care unit (NICU) with respiratory complications. METHODS: Women in this study (n=1290) were randomized into two groups: the dexamethasone group (n=645) and the control group (n=645). Women in the dexamethasone group received three doses of intramuscular dexamethasone 8mg, 12h apart, 48h before caesarean section. Women in the control group received intramuscular saline as a placebo in the same dosage as the dexamethasone group. PRIMARY OUTCOME: Comparison of NICU admission rates and the occurrence of neonatal respiratory morbidity between the two groups. RESULTS: The NICU admission rate for respiratory morbidity was significantly lower in the dexamethasone group compared with the control group [10/616 (1.6%) vs 24 (3.9%), respectively; p=0.014]. Antenatal administration of dexamethasone was significantly associated with almost 2.5-fold reduction in the risk of NICU admission for respiratory morbidity (relative risk 0.41, 95% confidence interval 0.2-0.86; number needed to treat ?43). CONCLUSION: Antenatal corticosteroids reduce the incidence of NICU admission with respiratory morbidity after elective caesarean section at term. PMID- 26905470 TI - Physiotherapy for pain and disability in adults with complex regional pain syndrome (CRPS) types I and II. AB - BACKGROUND: Complex regional pain syndrome (CRPS) is a painful and disabling condition that usually manifests in response to trauma or surgery. When it occurs, it is associated with significant pain and disability. It is thought to arise and persist as a consequence of a maladaptive pro-inflammatory response and disturbances in sympathetically-mediated vasomotor control, together with maladaptive peripheral and central neuronal plasticity. CRPS can be classified into two types: type I (CRPS I) in which a specific nerve lesion has not been identified, and type II (CRPS II) where there is an identifiable nerve lesion. Guidelines recommend the inclusion of a variety of physiotherapy interventions as part of the multimodal treatment of people with CRPS, although their effectiveness is not known. OBJECTIVES: To determine the effectiveness of physiotherapy interventions for treating the pain and disability associated with CRPS types I and II. SEARCH METHODS: We searched the following databases from inception up to 12 February 2015: CENTRAL (the Cochrane Library), MEDLINE, EMBASE, CINAHL, PsycINFO, LILACS, PEDro, Web of Science, DARE and Health Technology Assessments, without language restrictions, for randomised controlled trials (RCTs) of physiotherapy interventions for treating pain and disability in people CRPS. We also searched additional online sources for unpublished trials and trials in progress. SELECTION CRITERIA: We included RCTs of physiotherapy interventions (including manual therapy, therapeutic exercise, electrotherapy, physiotherapist-administered education and cortically directed sensory-motor rehabilitation strategies) employed in either a stand-alone fashion or in combination, compared with placebo, no treatment, another intervention or usual care, or of varying physiotherapy interventions compared with each other in adults with CRPS I and II. Our primary outcomes of interest were patient-centred outcomes of pain intensity and functional disability. DATA COLLECTION AND ANALYSIS: Two review authors independently evaluated those studies identified through the electronic searches for eligibility and subsequently extracted all relevant data from the included RCTs. Two review authors independently performed 'Risk of bias' assessments and rated the quality of the body of evidence for the main outcomes using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: We included 18 RCTs (739 participants) that tested the effectiveness of a broad range of physiotherapy-based interventions. Overall, there was a paucity of high quality evidence concerning physiotherapy treatment for pain and disability in people with CRPS I. Most included trials were at 'high' risk of bias (15 trials) and the remainder were at 'unclear' risk of bias (three trials). The quality of the evidence was very low or low for all comparisons, according to the GRADE approach.We found very low quality evidence that graded motor imagery (GMI; two trials, 49 participants) may be useful for improving pain (0 to 100 VAS) (mean difference (MD) -21.00, 95% CI 31.17 to -10.83) and functional disability (11-point numerical rating scale) (MD 2.30, 95% CI 1.12 to 3.48), at long-term (six months) follow-up, in people with CRPS I compared to usual care plus physiotherapy; very low quality evidence that multimodal physiotherapy (one trial, 135 participants) may be useful for improving 'impairment' at long-term (12 month) follow-up compared to a minimal 'social work' intervention; and very low quality evidence that mirror therapy (two trials, 72 participants) provides clinically meaningful improvements in pain (0 to 10 VAS) (MD 3.4, 95% CI -4.71 to -2.09) and function (0 to 5 functional ability subscale of the Wolf Motor Function Test) (MD -2.3, 95% CI -2.88 to 1.72) at long-term (six month) follow-up in people with CRPS I post stroke compared to placebo (covered mirror).There was low to very low quality evidence that tactile discrimination training, stellate ganglion block via ultrasound and pulsed electromagnetic field therapy compared to placebo, and manual lymphatic drainage combined with and compared to either anti-inflammatories and physical therapy or exercise are not effective for treating pain in the short-term in people with CRPS I. Laser therapy may provide small clinically insignificant, short-term, improvements in pain compared to interferential current therapy in people with CRPS I.Adverse events were only rarely reported in the included trials. No trials including participants with CRPS II met the inclusion criteria of this review. AUTHORS' CONCLUSIONS: The best available data show that GMI and mirror therapy may provide clinically meaningful improvements in pain and function in people with CRPS I although the quality of the supporting evidence is very low. Evidence of the effectiveness of multimodal physiotherapy, electrotherapy and manual lymphatic drainage for treating people with CRPS types I and II is generally absent or unclear. Large scale, high quality RCTs are required to test the effectiveness of physiotherapy-based interventions for treating pain and disability of people with CRPS I and II. Implications for clinical practice and future research are considered. PMID- 26905471 TI - Prevalence and Causes of Normal Exercise Oximetry in the Calf in Patients with Peripheral Artery Disease and Limiting Calf Claudication. AB - OBJECTIVE: In patients with claudication, an ankle brachial index (ABI) under 0.90 is considered to be abnormal and a sufficient argument for the arterial origin of exercise induced pain. Exercise transcutaneous oxygen pressure (Ex tcpO2) can provide evidence of exercise induced regional blood flow impairment (RBFI) and confirm the arterial origin of walking induced pain. The frequency with which calf Ex-tcpO2 remains apparently normal in patients with claudication and abnormal ABI is unknown. Causes of these discrepant results have yet to be analysed. METHODS: A retrospective analysis of 4575 Ex-tcpO2 tests performed on 3,281 patients was conducted. The focus was on patients with a history of calf claudication and ABI under 0.90. Duplicate or non-standard tests were excluded, as were patients with no pain or those able to walk more than 15 minutes (on a treadmill). Searches were conducted for possible explanations of normal calf Ex tcpO2 in the selected patients. RESULTS: Cardiorespiratory limitation was identified in 50 patients and isolated non-calf ischemia in 36 of the 106 patients selected. There was no obvious explanation during Ex-tcpO2, but clinical improvement after non-vascular treatment or total absence of improvement after a technically successful revascularisation was noted in 12 patients. Four patients were lost on follow up. Four patients improved after revascularisation, which suggests that the Ex-tcpO2 result was false negative. CONCLUSIONS: Ex-tcpO2 is negative in more than 20% of tests performed in patients with an ABI under 0.90 and a history of calf claudication. In most cases, when excluding re-tests and non-limiting or non-calf claudication on the treadmill, non-calf ischemia or a non-vascular limitation occurring during the test were observed. This observation supports both the value of treadmill testing in patients with calf claudication assumed to be of arterial origin (ABI<0.90) and the use of Ex-tcpO2 to detect non calf ischemia. PMID- 26905472 TI - Incidence of Healthcare Associated Infections After Lower Extremity Revascularization Using Antibiotic Treatment as a Marker. AB - OBJECTIVE/BACKGROUND: This register based study aimed to investigate the rate and pattern of healthcare associated infections (HCAI) in patients treated for lower extremity arterial disease, using antibiotic prescription as a surrogate for post operative HCAI. METHODS: A retrospective analysis of prospectively registered data on all patients treated with primary elective, open or endovascular, surgery for lower extremity arterial disease in Sweden between 2005 and 2010, was carried out. Antibiotic prescriptions were determined for three time periods (6 months pre-operative; 30 day post-operative, and 5 months extended post-operative). RESULTS: The cohort (n = 9894) included patients with claudication (27%, n = 2659), critical limb ischemia (rest pain without ulceration; 17%, n = 1681), and ulceration/gangrene (56%, n = 5552). Fifty-nine percent (n = 5865) of the procedures were endovascular interventions. The incidence of 30 day post operative antibiotic prescriptions was 33% (n = 3294). These were comprised of antibiotics for skin and soft tissue infections (67%, n = 2199); urinary tract infections (UTIs; 21%, n = 703); and respiratory tract infections (12%, n = 383). There was a 92% increase in the antibiotic prescription incidence rate for the 1 month post-operative period compared with the pre-operative period (p < .001). In the endovascular group, UTI antibiotics dominated the 30 day post-operative period for patients with claudication (p < .001). CONCLUSION: Antibiotic treatment can be a useful marker for post-discharge surveillance of HCAI in patients with lower extremity arterial disease. The incidence of post-operative HCAI after lower extremity revascularization may have previously been underestimated. PMID- 26905473 TI - The use of safety-seeking behavior in exposure-based treatments for fear and anxiety: Benefit or burden? A meta-analytic review. AB - There is a longstanding debate whether allowing safety-seeking behaviors (SSBs) during cognitive-behavioral treatment hampers or facilitates the reduction of fear. In this meta-analysis, we evaluate the impact of SSBs on exposure-based fear reduction interventions. After filtering 409 journal articles, 23 studies were included for systematic review of which 20studies were coded for meta analysis. For each study, the Standardized Mean Difference (SMD or Hedges' g) of self-reported fear was calculated at post-intervention. Two comparisons were distinguished: I) exposure without safety-seeking behavior (SSB-) versus baseline behavior (BL), and II) exposure with safety-seeking behavior (SSB+) versus BL. The results showed that average effect sizes were in favor of SSB-, (I: SMD=0.31, 95% CI [-0.04, 0.66]), and in favor of BL, (II: SMD=-0.13, 95% CI [-0.37, 0.11]). Neither of the effect sizes were statistically significant (I: Z=1.75, p=.08; II: Z=1.07, p=.28). The current meta-analysis could not provide compelling evidence supporting either the removal or addition of SSB during exposure. More systematic and statistically empowered replications, using comparable research methods, in (non-)clinical settings are needed. Novel insights from fear conditioning research may also shed light on the role of SSB in fear reduction. PMID- 26905474 TI - Italian Society for the Study of Diabetes (SID)/Italian Endocrinological Society (SIE) guidelines on the treatment of hyperglycemia in Cushing's syndrome and acromegaly. AB - BACKGROUND: Hyperglycemia is a common feature associated with states of increased growth hormone secretion and glucocorticoid levels. AIMS: The purpose of these guidelines is to assist clinicians and other health care providers to take evidence-based therapeutic decisions for the treatment of hyperglycemia in patients with growth hormone and corticosteroid excess. METHODOLOGY: Both the SID and SIE appointed members to represent each society and to collaborate in Guidelines writing. Members were chosen for their specific knowledge in the field. Each member agreed to produce--and regularly update--conflicts of interest. The Authors of these guidelines prepared their contributions following the recommendations for the development of Guidelines, using the standard classes of recommendation shown below. All members of the writing committee provided editing and systematic review of each part of the manuscript, and discussed the grading of evidence. Consensus was guided by a systematic review of all available trials and by interactive discussions. PMID- 26905475 TI - Divergent electrophysiologic profile of fluconazole and voriconazole in an experimental whole-heart model of proarrhythmia. AB - In several case reports a prolongation of the QT-interval and even proarrhythmic effects of fluconazole and voriconazole were reported. The aim of the present study was to investigate if application of fluconazole or voriconazole has the potential to provoke polymorphic ventricular tachycardia in a sensitive model of proarrhythmia. In female rabbits, fluconazole (10, 30 and 50 uM, n=6) and voriconazole (10, 30 and 50 uM, n=6) were infused after obtaining baseline data. Eight endocardial and epicardial monophasic action potentials and a simultaneously recorded 12-lead ECG showed a significant QT prolongation after application of fluconazole as compared with baseline (10 uM:+12 ms, 30 uM:+22 ms, 50 uM:+37 ms; P<0.05) accompanied by an increase of action potential duration (APD90). Administration of voriconazole also induced QT prolongation (30 uM:+10 ms, 50 uM:+20 ms, P<0.05). Spatial dispersion of repolarization remained stable in voriconazole-treated hearts while fluconazole induced a significant increase (30 uM:+15 ms, 50 uM:+16 ms; P<0.05). Lowering of potassium concentration in bradycardic AV-blocked hearts did not provoke any early afterdepolarizations (EADs) or polymorphic ventricular tachycardia in voriconazole-treated hearts. Application of fluconazole led to the reproducible induction of EADs in 4 of 6 hearts and polymorphic ventricular tachycardia in 3 of 6 hearts (36 episodes). In the present study, voriconazole demonstrated a safe electrophysiologic profile despite significant QT prolongation. In contrast, fluconazole led to a more marked prolongation of myocardial repolarization combined with a more marked increase of dispersion of repolarization. These results imply that application of fluconazole might be torsadogenic and the QT-interval should be closely monitored. PMID- 26905476 TI - PI3K and ERK1/2 kinase inhibition potentiate protease inhibitor to attenuate allergen induced Th2 immune response in mouse. AB - Proteases affect immune response by activating PI3K, ERK1/2 and p38 kinase. In present study, therapeutic effect of PI3K, ERK1/2 and p38 kinase inhibitor in combination with serine protease inhibitor was evaluated in cockroach extract (CE) induced airway inflammatory disease. Mice were sensitized on day 0, 7 and 14 and challenged on day 27, 28 and 29 with CE. Mice were given PI3K, ERK1/2 and the p38 kinase inhibitor (iPI3K, iERK1/2 and the ip38) alone or with serine protease inhibitor 4-(2-Aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF), 1h before challenge. On day 30 airway resistance of mice were determined and euthanized to collect blood, BAL fluid and lung for analysis. CE immunized mice showed PI3K, ERK1/2 and p38 kinase activation, increased airway resistance, cellular infiltration, Th2 cytokines IgE and IgG1. AEBSF given to mice reduced the CE induced allergic response. AEBSF given in combination of iPI3K/iERK1/2 reduced cellular infiltration in lungs. Furthermore, iPI3K/iERK1/2 with AEBSF significantly reduced the CE induced Th2 cytokines in comparison to monotherapy of kinase inhibitor and AEBSF (P<0.05). The combination of iPI3K/iERK1/2 with AEBSF enhanced IL-12 level that could further provide a mean of Th2 reduction. Best effect in reduction of allergic response in mice was observed on administration of AEBSF with iPI3K. Conclusively, the combination of PI3K kinase inhibitor with AEBSF reduced allergen induced airway response and has therapeutic potential for add-on therapy in allergic airway disease. PMID- 26905477 TI - Long-term evaluation of a liquid crystal polymer (LCP)-based retinal prosthesis. AB - OBJECTIVE: The aim of this study is to evaluate the long-term reliability of a recently presented liquid crystal polymer (LCP) -based retinal prosthesis in vitro as well as in vivo. Because an all-polymer implant introduces another intrinsic leak type due to gas permeation, for which the traditional helium leak test for metallic packages was not designed to quantify, a new method to investigate its durability is required. APPROACH: We designed and carried out a series of reliability tests specifically for all-polymer implants by quantitatively investigating moisture ingress through various pathways of the polymer surface, and the polymer-polymer and polymer-metal adhesions. Moisture permeation through the bulk material was estimated by analytic calculation, while water ingress through the adhesively sealed LCP-LCP and LCP-metal interfaces was investigated using the separate parts of an electrode array and a package in an accelerated aging condition. In vivo tests were done in rabbits to examine the long-term biocompatibility and implantation stability by fundus observation and optical coherence tomography (OCT) imaging. MAIN RESULTS: The analytic calculation estimated good barrier properties of the LCP. Samples of the LCP based electrode array failed after 114 days in 87 degrees C saline as a result of water penetration through the LCP-metal interface. An eye-conformable LCP package survived for 87 days in an accelerated condition at 87 degrees C. The in vivo results confirmed that no adverse effects were observed around the retina 2.5 years after the implantation of the device. SIGNIFICANCE: These long-term evaluation results show the potential for the chronic use of LCP-based biomedical implants to provide an alternative to traditional metallic packages. PMID- 26905479 TI - Drug policy: getting over the 20th century. PMID- 26905478 TI - Production of hepatitis E virus-like particles presenting multiple foreign epitopes by co-infection of recombinant baculoviruses. AB - Hepatitis E virus (HEV) causes not only endemics via a fecal-oral route but also sporadic cases via zoonotic transmission or blood transfusion. HEV-like particles (HEV-LP) produced by using a baculovirus expression system are considered a candidate for mucosal vaccines for HEV infection. In this study, we attempted to produce a chimeric HEV-LP presenting various foreign epitopes on its surface. Expression of the recombinant capsid proteins carrying a myc- or FLAG-tag inserted between amino acid residues 488 and 489, which are located in the exterior loop on the protruding domain of the HEV capsid, resulted in the production of recombinant HEV-LP. Although expression of the recombinant capsid protein carrying the HA-tag inserted at the same site failed to produce any particles, co-expression with the myc-tagged capsid protein successfully yielded a chimeric HEV-LP consisting of both recombinant capsid proteins. Immunoprecipitation analyses confirmed that the chimeric particles present these foreign epitopes on the surface. Similar results were obtained for the expression of the recombinant capsid proteins carrying neutralizing epitopes of Japanese encephalitis virus. These results suggest the chimeric HEV-LP system provides a novel vaccine carrier that can accommodate multiple neutralizing epitopes on its surface. PMID- 26905480 TI - The increasing global health priority of substance use in young people. AB - Substance use in young people (aged 10-24 years) might disrupt key periods of transition that occur as the adolescent brain undergoes cognitive and emotional development, and key psychosocial transitions are made. Adolescence is the peak time for initiation of substance use, with tobacco and alcohol usually preceding the use of illicit drugs. Substantial variation is noted between countries in the levels, types, and sequences of substance use in young people, indicating that a young person's use of substances depends on their social context, drug availability, and their personal characteristics. The Global Burden of Disease (GBD) 2013 study suggests that the burden attributable to substance use increases substantially in adolescence and young adulthood. In young men aged 20-24 years, alcohol and illicit substance use are responsible for 14% of total health burden. Alcohol causes most health burden in eastern Europe, and illicit drug burden is higher in the USA, Canada, Australia, New Zealand, and western Europe. Large gaps exist in epidemiological data about the extent of drug use worldwide and much of what we know about the natural history of substance use comes from cohort studies in high-income countries undertaken decades ago, which hinders effective global policy responses. In view of the global epidemiological transitions from diseases of poverty to non-communicable diseases, the burden of disease and health risks among adolescents and young adults is likely to change substantially, in ways that will no doubt see substance use playing an increasingly large part. PMID- 26905481 TI - Prevention, early intervention, harm reduction, and treatment of substance use in young people. AB - We did a systematic review of reviews with evidence on the effectiveness of prevention, early intervention, harm reduction, and treatment of problem use in young people for tobacco, alcohol, and illicit drugs (eg, cannabis, opioids, amphetamines, or cocaine). Taxation, public consumption bans, advertising restrictions, and minimum legal age are effective measures to reduce alcohol and tobacco use, but are not available to target illicit drugs. Interpretation of the available evidence for school-based prevention is affected by methodological issues; interventions that incorporate skills training are more likely to be effective than information provision-which is ineffective. Social norms and brief interventions to reduce substance use in young people do not have strong evidence of effectiveness. Roadside drug testing and interventions to reduce injection related harms have a moderate-to-large effect, but additional research with young people is needed. Scarce availability of research on interventions for problematic substance use in young people indicates the need to test interventions that are effective with adults in young people. Existing evidence is from high-income countries, with uncertain applicability in other countries and cultures and in subpopulations differing in sex, age, and risk status. Concerted efforts are needed to increase the evidence base on interventions that aim to reduce the high burden of substance use in young people. PMID- 26905482 TI - Why young people's substance use matters for global health. AB - During puberty, when young people are completing their education, transitioning into employment, and forming longer-term intimate relationships, a shift in emotional regulation and an increase in risky behaviour, including substance use, is seen. This Series paper considers the potential effects of alcohol, tobacco, and illicit drug use during this period on: social, psychological, and health outcomes in adolescence and young adulthood; role transitions, and later health and social outcomes of regular substance use initiated in adolescence; and the offspring of young people who use substances. We sourced consistent support for causal relations between substance use and outcomes and evidence of biological plausibility from different but complementary research designs. Many adverse health and social outcomes have been associated with different types of substance use. The major challenge lies in deciding which are causal. Furthermore, qualitatively different harms are associated with different substances, differences in life stage when these harms occur, and the quality of evidence for different substances and health outcomes varies substantially. The preponderance of evidence comes from a few high-income countries, thus whether the same social and health outcomes would occur in other countries and cultures is unclear. Nonetheless, the number of harms that are causally related to substance use in young people warrant high-quality research design interventions to prevent or ameliorate these harms. PMID- 26905483 TI - Bone Marrow Synoptic Reporting for Hematologic Neoplasms: Guideline From the College of American Pathologists Pathology and Laboratory Quality Center. AB - CONTEXT: -There is ample evidence from the solid tumor literature that synoptic reporting improves accuracy and completeness of relevant data. No evidence-based guidelines currently exist for synoptic reporting for bone marrow samples. OBJECTIVE: -To develop evidence-based recommendations to standardize the basic components of a synoptic report template for bone marrow samples. DESIGN: -The College of American Pathologists Pathology and Laboratory Quality Center convened a panel of experts in hematopathology to develop recommendations. A systematic evidence review was conducted to address 5 key questions. Recommendations were derived from strength of evidence, open comment feedback, and expert panel consensus. RESULTS: -Nine guideline statements were established to provide pathology laboratories with a framework by which to develop synoptic reporting templates for bone marrow samples. The guideline calls for specific data groups in the synoptic section of the pathology report; provides a list of evidence based parameters for key, pertinent elements; and addresses ancillary testing. CONCLUSION: -A framework for bone marrow synoptic reporting will improve completeness of the final report in a manner that is clear, succinct, and consistent among institutions. PMID- 26905485 TI - Government slow to improve services for people with learning disabilities, report finds. PMID- 26905484 TI - Construction and in vitro testing of a cellulose dura mater graft. AB - INTRODUCTION: Cerebrospinal fluid (CSF) leaks are a common complication after cranial and spinal surgery and are associated with increased morbidity. Despite continuous research in this field, this problem is far from solved. In this paper, we describe the construction and testing of a bacterial cellulose (BC) membrane as a new dural patch. MATERIALS AND METHODS: The synthesis of BC was performed using Gluconacetobacter hansenii (ATCC 23769) and films were sterilized by autoclaving. The membranes were seeded with human dural fibroblasts. Growth, shape, and cell viability were assessed after 4 weeks. RESULTS: Normally shaped fibroblasts were seen on the BC grafts; confocal microscopy showed cells inside the structure of the mesh. Both viable and nonviable cells were present. Cellular attachment and viability were confirmed by replating of the membranes. DISCUSSION: BC membranes are used in clinical practice to improve skin healing. In the presence of water, they form an elastic, nontoxic, and resistant biogel that can accommodate collagen and growth factors within their structure, thus BC is a good candidate for dural graft construction. PMID- 26905486 TI - Effect of arteriovenous fistula and usage of arm with fistula on bone mineral density in hemodialysis patients. AB - We aimed to determine the incidence of osteoporosis in hemodialysis patients, to evaluate the differences due to arteriovenous fistula on bone mineral density (BMD) and to investigate whether usage of arm with fistula has an effect on BMD. In this cross-sectional study, 96 patients with chronic renal disease undergone to dialysis were included. Place of fistula (radial and brachial) and dominant hand were recorded. All patients were asked to complete Likert's scale in order to determine the frequency of their usage of arm with fistula. Patients were assigned in two groups: age >51 and < 50 years. Age-matched control group included 60 subjects. BMD measurements were done on lumbar vertebra, femur and both forearms. BMD measurement of proximal femur and total radius were significantly lower in patients >50 years compared to healthy controls and bone density measurement of lumbar vertebra, proximal femur, 1/3 distal and total radius were significantly lower in patients < 50 years compared to healthy controls (p < 0.05). BMD measurement was significantly lower in arms with fistula, especially with radial fistula, compared to both arms without fistula and healthy controls (p < 0.05). When all patients were evaluated, BMD scores were lowering by increasing age, duration of dialysis and fistula and decreasing usage of arm with fistula. BMD in hemodialysis patients is lower than normal population. BMD of arm with fistula is lower than arm without fistula and healthy controls. Both radial and brachial fistula affect negatively ipsilateral BMD. Movement of arm with fistula has positive effects on BMD. PMID- 26905487 TI - Framework to Evaluate Exposure Relevance and Data Needs for Risk Assessment of Nanomaterials using in Vitro Testing Strategies. AB - This article presents a multistage framework for evaluating the strength of evidence of nanomaterial (NM) exposure characterization data to optimize the utility of in vitro testing strategies for human health risk assessment. This framework is intended to aid risk assessors in evaluating the relevance of data from in vitro tests and to optimize the development of new in vitro testing strategies. The initial stage frames the exposure scenarios of interest in advance of testing to incorporate aspects such as release points, route of exposure, biological and environmental transformations, dose metrics, and biological targets in subsequent stages. The second stage considers characterization in the context of a realistic exposure and the third stage involves designing a testing strategy based on expected exposure conditions. For the fourth and final stage, we propose a matrix approach to evaluate the strength of evidence obtained in the first three stages as a basis for determining the best combination of test conditions and analytical methods available to characterize and measure exposure based on the NM type. This approach can also be used to evaluate existing data for their relevance to the expected exposure scenario and to further develop and optimize in vitro testing strategies. Implementation of the proposed strategy will generate meaningful information on NM properties and their interaction with biological systems, based on realistic exposure scenarios, which will be cost effective and can be applied for assessing risk and making intelligent regulatory decisions regarding the use and disposal of NMs. PMID- 26905488 TI - Detection and strain differentiation of infectious bronchitis virus in tracheal tissues from experimentally infected chickens by reverse transcription-polymerase chain reaction. Comparison with an immunohistochemical technique. AB - Oligonucleotide pairs were constructed for priming the amplification of fragments of nucleocapsid (N) protein and spike glycoprotein (S) genes of avian infectious bronchitis virus (IBV) by reverse transcriptionpolymerase chain reaction (RT PCR). One oligonucleotide pair amplified a common segment of the N-gene and could detect various strains of IBV in allantoic fluid from inoculated chicken embryos, and in tracheal tissue preparations from experimentally infected chickens. Four pairs of oligonucleotides selectively primed the amplification of the S1 gene of Massachusetts/Connecticut, D1466, D274/D3896 and 793B strains of IBV, respectively. Groups of specific pathogen free chickens were experimentally inoculated with the Massachusetts (H120, M41), the D1466 and the 793B strains of IBV, and tracheal tissue preparations were made from each bird for RT-PCR and for immunohistochemistry (IHC) up to 3 days post-inoculation. The N-gene RT-PCR detected IBV in 82% of the chickens, while IHC only detected IBV in 60%. This difference was significant (P<0.02). The detection rate by N-gene RT-PCR varied from 67 to 100% for the various strains of IBV inoculated. The S1 gene oligonucleotide pairs were applied to the same tissue preparations and they detected specifically the Massachusetts (M41 and H120), the D1466 and the 793B strains of IBV at rates varying between 58 and 92%. When the mixtures of the primers were applied, the detection rate in tissue preparations was reduced to the level of 50 to 67%. It is concluded that the direct detection of IBV in tracheal tissues by RT-PCR is more sensitive than IHC and that the RT-PCR technique is able to distinguish between types of IBV. PMID- 26905489 TI - Experiences with multispecies polymerase chain reaction and specific oligonucleotide probes for the detection of Mycoplasma gallisepticum and Mycoplasma synoviae. AB - Amplified fragments of the rDNA coding for 16S rRNA of Mycoplasma gallisepticum (MG) and Mycoplasma synoviae (MS) were blotted on nylon membranes, followed by dot-blot detection with two species-specific digoxigenin-(DIG)-labeled oligonucleotide probes. The sensitivity and specifity of the tests were determined in titration studies with purified homologous and heterologous DNA. With the detection protocol used, the MSYV8/31 probe showed 100% specifity for MS, while both MG and the related species Mycoplasma imitans were recognized by the MGAV8/31 probe. Both DIG-labeled oligonucleotides gave positive results in the colorimetric assay with 10 to 100 ng homologous non-amplified DNA and polymerase chain reaction (PCR) amplificates of 100 fg homologous template DNA. There was no reaction with heterologous strains when amplificates starting with a 106-fold amount of template DNA (100 ng) were tested in dot-blots. The suitability for field samples was demonstrated with tracheal swabs from turkeys and chickens, and the results were compared with mycoplasma growth in cultures of the same swabs. Both tests had an accuracy of over 95%, a high sensitivity and specificity, and high predictive values of positive or negative results. There was no significant difference between the results obtained by the two methods. PCR in combination with dot-blotting is a relatively simple method for the detection of mycoplasma infections, and a valuable extension of current diagnostic tools. PMID- 26905490 TI - Granular cell tumour in an endangered Puerto Rican Amazon parrot (Amazon vittata ). AB - A 3 cm diameter mass from the metacarpus of a Puerto Rican Amazon parrot was diagnosed as a granular cell tumour based on light microscopy. The cytoplasmic granules were periodic-acid Schiff positive and diastase resistant. Ultrastructural characteristics of the cells included convoluted nuclei and the presence of numerous cytoplasmic tertiary lysosomes. This is only the second granular cell tumour reported in a bird. We speculate that most granular cell tumours are derived from cells that are engaged in some type of cellular degradative process, creating a similar morphologic appearance, but lacking a uniform histogenesis. PMID- 26905491 TI - Enteropathogenic Escherichia coli in Psittaciformes. AB - A total of 103 Escherichia coli isolates from psittaciform birds were examined for the presence of genes coding for shigatoxin 1 (Stx1), shigatoxin 2 (Stx2) and for intimin (eae), using the polymerase chain reaction (PCR). Sixty-eight E. coli strains were isolated from necropsy cases and faecal samples, the other 35 were from 205 cloacal swabs from Psittaciformes with various conditions. All isolates were tested for enterohaemorrhagic E. coli-haemolysin (HlyEHEC), some also for Stx production, but there was no geno-typic or phenotypic evidence of Stx in any of them. Seven isolates, six from birds with diarrhoea, harboured the eae gene, three of them belonging to the O110:H6 serotype, one each to serotypes O153:H10, O131:H-, O63:H6 and Osp:H6. These seven eae-positive strains were negative for shigatoxin and HlyEHEC, and the hlyEHEC gene was not detectable by PCR. However, a PCR amplifying the enteropathogenic E. coli (EPEC)-specific bundle-forming pili structural gene bfpA detected four bfpA positive strains (three of serotype O110:H6, one O131:H-) among the seven eae positive strains, which classifies them as EPEC. Our findings suggest that shigatoxin-producing E. coli are uncommon, but that EPEC should be considered as potential pathogens in psittaciform birds, which may be a source of human EPEC infections. PMID- 26905492 TI - Efficacy of inactivated whole-cell vaccines against streptococcosis in pigeons. AB - Two experimental vaccines were developed and evaluated for their efficacy against Streptococcus gallolyticus septicaemia in pigeons. Both vaccines contained whole cell formaldehyde-inactivated S. gallolyticus serotype 1 bacteria and a mineral oil adjuvant. The supernatant of a S. gallolyticus broth culture was also added to one of the vaccines. Four groups of 10 pigeons were inoculated either once, or twice, with a 4-week interval, with one of the vaccines. Four weeks after the last vaccination, pigeons were challenged by intravenous inoculation with S. gallolyticus serotype 1. Morbidity after infection was not significantly different between groups of pigeons vaccinated with the two vaccines. In groups of pigeons vaccinated once, morbidity after infection ranged from 50 to 70%; in pigeons vaccinated twice, morbidity was 10 to 30%. In a non-vaccinated inoculated control group, the morbidity was 80%. It was concluded that double vaccination can result in some clinical protection against streptococcosis in pigeons. PMID- 26905493 TI - Experimental toxoplasmosis in house sparrows (Passer domesticus). AB - A total of 31 house sparrows (Passer domesticus) were divided into five groups of six to seven birds. Birds were infected per os with 1, 10, 102, 103 and 104 oocysts of Toxoplasma gondii of the K1 strain, respectively. When the general health, production of antibodies against T. gondii and isolation positivity of the sparrows were examined in weeks 3, 7 and 12 post-infection (p.i.), no clinical signs of toxoplasmosis were observed. Seroprevalences ascertained in weeks 3, 7, and 12 p.i. were 64% (18 positive/28 tested), 95% (21/22) and 70% (7/10) when tested by indirect immunofluorescence (titre 20); 54% (15/28), 59% (13/22) and 70% (7/10) when tested by the latex agglutination test (titre 20); and 59% (4/7), 0% (0/12) and 20% (2/10) when tested by the Sabin Feldman dye test (titre 4), respectively. T. gondii was re-isolated from 45% (13/29) infected sparrows. House sparrows were found to exhibit some resistance to the K1 strain of T. gondii after oocyst infection, and the results suggest that sparrows may not be a significant source of environmental infection. PMID- 26905494 TI - Identification of members of the Pasteurellaceae isolated from birds and characterization of two new taxa isolated from psittacine birds. AB - A collection of 43 unclassified members of the Pasteurellaceae, most of which were obtained from lesions, were investigated using an extensive battery of phenotypical tests as well as by ribotyping. The isolates had been made from Anser anser forma (f) domestica (d), Agapornis fischer, Amazona spp., Ara macao, Columba livia f.d., Melanopsittacus undulatus, and Psittacus erithacus. Comparison of results with those obtained from reference strains allowed classification of 25 strains. Three strains were identified as Pasteurella dagmatis, P. sp. A, and [P.] aerogenes, respectively. Twenty strains were classified as taxon 3 and two as taxon 14. Eighteen strains, all originating from psittacine species, belonged to two new taxa, tentatively named Bisgaard taxon 33 and taxon 37. Characters obtained with taxon 33 allowed classification within the family Pasteurellaceae, while the final classification of taxon 37 remains to be investigated. The present investigation underlines the problems confronting diagnostic laboratories attempting to identify members of the family Pasteurellaceae isolated from birds. PMID- 26905495 TI - Immunocompetence and resistance to marble spleen disease of broiler- and layer type pure lines of chickens. AB - The intent of this study was to evaluate, under concurrent conditions, certain responses that may be important in chicken breeding and growing. Three commercial broiler pure lines (A, B, and C) and two experimental White Leghorn lines selected for high (HAS) and low (LAS) antibody response to sheep red blood cells were evaluated concurrently for humoral and cell-mediated immunocompetence, resistance to marble spleen disease virus (MSDV), relative asymmetry (RA), and comb weight. Chicks were injected with 0.1 ml of 0.25% SRBC at 21 days of age. Antibody response 6 days after injection was highest in line HAS. Titres for the commercial lines were similar to those in line LAS. The cutaneous basophil hypersensitivity test, an in vivo cell-mediated immune response, was measured as the increase in toe-web thickness 24 h after an injection with T-cell mitogen phytohaemagglutinin (PHA)-P or -M into a sample of chicks at 9 days of age and a different sample of chicks at 20 days of age. PHA-P elicited greater responses than PHA-M at both ages. The pattern among stocks, however, differed depending upon age. Responses at 9 days were greater for the Leghorn than broiler lines, while at 20 days, responses were greater in lines A and LAS than in lines B, C, and HAS. Resistance to MSDV challenge differed among stocks, with the ranking for resistance being C>(A=B=LAS)>HAS. Rankings of RA for normal thickness of the toe web between the third and fourth digits at 9 days of age were (HAS=LAS)>(A=B=C). There were no differences in RA among stocks at 20 days of age. There was a significant line by sex interaction for relative comb weight, due to differences between lines for males but not females. Data from this study suggest that competence in one arm of the immune system is not a reliable measure of general immunocompetence, nor is it a measure of resistance in general. PMID- 26905496 TI - Detection of exogenous and endogenous avian leukosis virus in commercial chicken eggs using reverse transcription and polymerase chain reaction assay. AB - Avian leukosis retroviruses (ALV) cause lymphomas and other cancers in chickens. Previous studies have used enzyme-linked immunosorbent assays (ELISA) and indirect immunofluorescence assays (IFA) to detect ALV p27 group-specific antigens (GSA) in commercial chicken eggs. In the poultry industry eradication programme against exogenous ALV, ELISA assays are used to identify chickens infected with the virus. The inability of ELISA and IFA assays to discriminate between ALV GSA of endogenous or exogenous origin, and actual virus, have limited rigorous assessments of viral transmission dynamics. Here, we report the use of a newly developed reverse transcriptase-polymerase chain reaction (RT-PCR) assay, with direct sequencing of the RT-PCR product, to show endogenous and exogenous ALV in albumen from unfertilized chicken eggs. We found that 95% of 20 eggs from ALV-exposed commercial chickens and 14.2% of 240 egg samples from 20 randomly chosen New Orleans retail stores were ALV-positive by RT-PCR. In comparison, only 2.5% of the same egg samples from the retail stores were positive by ELISA. Corresponding direct sequencing of randomly chosen RT-PCR products showed that four of six egg samples contained endogenous ALV, while two of the six samples were positive for exogenous subgroup A ALV. The finding of endogenous subgroup E ALV in unfertilized chicken eggs emphasizes that the transmission of endogenous ALV is common and should be considered in the implementation of ALV eradication programmes by the poultry industry. PMID- 26905497 TI - Visceral lesions caused by Yersinia pseudotuberculosis, serotype II, in different species of bird. AB - The size and distribution of histological lesions was studied in 14 cases of avian pseudotuberculosis using a combination of serotype-specific immunohistochemistry and image analysis. The material was derived from recent and archival cases in six canaries (Serinus canaria), two zebra finches (Poephila guttata), three psittaciformes (a kaka, Nestor meriondalis, one rainbow lorikeet, Trichoglossus mollucanus, and one budgerigar, Melopsittacus undulatus), and three New Zealand wood pigeons (Hemiphaga novaeseelandiae). The disease observed in the passerine species appeared to have an acute clinical course and the bacterial lesions were predominately enteric. In the pigeons and the psittaciformes examined, the clinical course of the disease was more chronic in nature and involved the liver and spleen. A correlation was found between the amount of stainable iron in the liver of affected birds and the area of bacterial lesions. All of the 11 strains of Yersinia pseudotuberculosis isolated from fresh necropsy material were serotype II, as determined using a standard serum agglutination test. Immunohistochemistry indicated the presence of antigen(s) common to serotype II in histological material from confirmed cases and in another three cases where the organism had been cultured but the serotype not specified. The in vitro virulence characteristics and plasmid profiles of Y. pseudotuberculosis isolates were also determined. PMID- 26905500 TI - Tom Newman Memorial Award. PMID- 26905498 TI - Dual infection of turkey poults with avian pneumovirus and Mycoplasma synoviae. AB - Poults were infected with avian pneumovirus (APV) at 1-day-old, followed by Mycoplasma synoviae (Ms) 3 days later. Dual infection did not cause an increase in severity of clinical disease, or gross and microscopic lesions due to APV. The patterns of virus and Ms isolations from tracheal swabs or tissues from single and dual infected groups were similar. Ms infection did not induce Ms antibodies, nor did it affect seroconversion to APV in the dual infection. PMID- 26905501 TI - Glycated hemoglobin cannot yet be proposed as a screening tool for cystic fibrosis related diabetes. AB - With improved life expectancy of cystic fibrosis (CF) patients, CF-related diabetes (CFRD) has become a major complication. The oral glucose tolerance test (OGTT) is the standard test to detect it. However, the use of OGTT is controversial, in addition to being a burden for patients and the treatment team. Research to find alternative ways of testing is ongoing. While some propose that glycated hemoglobin (HbA1c) may be an effective alternative, our past results suggest otherwise. A new analysis involving the OGTT and HbA1c values of 207 patients, between 2004 and 2015, proposes that the threshold of a lower value of HbA1c of >=5.8%(39.9 mmol/mol) gives a sensitivity of 68.2% and a specificity of 60.5%. With such sensitivity to identify patients in need of an OGTT, 31.8% of CFRD diagnosis would be missed if the suggested HbA1c value of >=5.8% was used as a screening tool to identify patients in need of OGTTs. Considering our results, we believe the HbA1c does not possess the characteristics of a suitable screening test for CFRD. PMID- 26905502 TI - Finding patterns and learning words: Infant phonotactic knowledge is associated with vocabulary size. AB - Native language statistical regularities about allowable phoneme combinations (i.e., phonotactic patterns) may provide learners with cues to support word learning. The current research investigated the association between infants' native language phonotactic knowledge and their word learning progress, as measured by vocabulary size. In the experiment, 19-month-old infants listened to a corpus of nonce words that contained novel phonotactic patterns. All words began with "illegal" consonant clusters that cannot occur in native (English) words. The rationale for the task was that infants with fragile phonotactic knowledge should exhibit stronger learning of the novel illegal phonotactic patterns than infants with robust phonotactic knowledge. We found that infants with smaller vocabularies showed stronger phonotactic learning than infants with larger vocabularies even after accounting for general cognition. We propose that learning about native language structure may promote vocabulary development by providing a foundation for word learning; infants with smaller vocabularies may have weaker support from phonotactics than infants with larger vocabularies. Furthermore, stored vocabulary knowledge may promote the detection of phonotactic patterns even during infancy. PMID- 26905503 TI - Effects of hydrostatic pressure on microtubule organization and nucleus changes in gynogenetically activated eggs of olive flounder (Paralichthys olivaceus). AB - Fluorescent double-labeled technique was used to investigate the effects of hydrostatic pressure on microtubule organization and nucleus in gynogenetically activated eggs of olive flounder (Paralichthys olivaceus). The parameter of hydrostatic pressure treatment was 600 kg/cm(2) for 6 minutes at prometaphase of the first mitosis. The data showed that nucleus and microtubule changes of the diploid control were basically similar to those of the haploid one (5 minutes behind those of the diploid control). Nuclear diameter of the haploid embryo was significantly smaller than that of the diploid one (P < 0.01). The ploidy of chromosome set could be determined basing on nuclear diameter. The results of nuclear diameter measurement and the ratio of developmentally delayed embryo showed that the chromosome set was not doubled during the second cell cycle, the first cleavage proceeded normally; but that of about 80% treated embryo was doubled during the third cell cycle, the second cleavage was inhibited. Microtubules were disassembled, and nucleation capacity of centrosome was just temporarily inhibited by pressure treatment. Centrosome renucleated microtubule, and a bipolar spindle reassembled 15 minutes after treatment, leading to occurrence of the first cleavage. During the second cell cycle, about 80% treated embryo had a single centrosome and formed a unipolar spindle in both blastomeres. After prometaphase, chromosomes spread around for about 20 minutes instead of aligning on the equatorial plane, then assembled and formed one large nucleus without anaphase separation. The second cleavage was inhibited, and the chromosome set was doubled. The data indicated that the chromosome set doubling of mitogynogenetic diploid induced by hydrostatic pressure treatment, which performed at prometaphase of the first mitosis, mainly resulted from the inhibition of the second cleavage rather than the first one. This study is the first to adapt fluorescent double-labeled technique to investigate the mechanism on chromosome set doubling of mitotic gynogenesis induction. This study will offer theoretical support for mitogynogenetic diploid induction in marine fish. PMID- 26905504 TI - Changes in proliferating and apoptotic markers in the oviductal magnum of chickens during sexual maturation. AB - The avian oviduct is characterized by dynamic hormonal, biochemical, and cellular changes during its development. To better understand the molecular mechanisms regulating proper development of this organ in birds, the rate of cell proliferation and apoptosis as well as these processes-related gene expressions in the chicken oviduct during the sexual maturation were examined. The oviducts were isolated from Hy-Line Brown chickens at 2-week intervals from 10 to 16 weeks of age, and at 17 weeks, i.e. just after the onset of egg laying. In the tissue from the middle part of the oviduct (the magnum) the following parameters were tested: (1) proliferating (proliferating cell nuclear antigen [PCNA]-positive) and apoptotic (Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive) cells, (2) mRNA expression of bcl-2, caspases 2, 3, 8, and 9, PCNA, survivin-142, and ovalbumin by quantitative real-time polymerase chain reaction, (3) protein expression of Bcl-2, PCNA, and caspases 3 and 9 by Western blot, (4) activity of caspases 2, 3, 8, and 9 by fluorometric method, and (5) localization of Bcl-2 and caspases by immunohistochemistry. It was found that the number of proliferating cells per unit area did not change during the examined period. The number of apoptotic cells in the oviductal wall remained on the same level until 14 weeks of age followed by a gradual decrease, reaching the lowest number at 17 weeks. The mRNA expression of all caspases and Bcl-2 gradually decreased during maturation, and PCNA decreased after 14 weeks of age. Survivin 142 mRNA level increased in 14-week-old chickens and then diminished, whereas ovalbumin expression was dramatically elevated in birds 16 weeks old and older. Patterns of protein expression of Bcl-2, PCNA, and caspases and activity of caspases were similar to mRNA, although not as pronounced. In the wall of the magnum the apoptotic cells and examined proteins were localized predominantly in the mucosa (surface epithelium and tubular glands). In summary, the results obtained provide some evidence of changes in selected proliferation- and apoptosis-related gene expression, alterations in activity of multiple apoptotic markers, and differences in the frequency of proliferating and apoptotic markers between mucosa and stroma in the oviductal magnum during the sexual maturation. Concluding, we suggest that Bcl-2, PCNA, survivin-142, and some caspases may cooperatively orchestrate a cascade of events mainly related to the cell proliferation, apoptosis, and differentiation in the chicken oviduct over the course of its development. PMID- 26905505 TI - The role of the endoplasmic reticulum stress in stemness, pluripotency and development. AB - The molecular machinery of endoplasmic reticulum (ER) integrates various intracellular and extracellular cues to maintain homeostasis in diverse physiological or pathological scenarios. ER stress and the unfolded protein response (UPR) have been found to mediate molecular and biochemical mechanisms that affect cell proliferation, differentiation, and apoptosis. Although a number of reviews on the ER stress response have been published, comprehensive reviews that broadly summarize ER physiology in the context of pluripotency, embryonic development, and tissue homeostasis are lacking. This review complements the current ER literature and provides a summary of the important findings on the role of the ER stress and UPR in embryonic development and pluripotent stem cells. PMID- 26905506 TI - Concussion Characteristics in High School Football by Helmet Age/Recondition Status, Manufacturer, and Model: 2008-2009 Through 2012-2013 Academic Years in the United States. AB - BACKGROUND: Football helmets used by high school athletes in the United States should meet the National Operating Committee on Standards for Athletic Equipment performance standards. Despite differences in interior padding and exterior shells, all football helmets should provide comparable protection against concussions. Yet, debate continues on whether differences in the rates or severity of concussions exist based on helmet age/recondition status, manufacturer, or model. PURPOSE: To investigate whether high school football concussion characteristics varied by helmet age/recondition status, manufacturer, and model. STUDY DESIGN: Descriptive epidemiological study. METHODS: High school football concussion and helmet data were collected from academic years 2008-2009 through 2012-2013 as part of the National High School Sports-Related Injury Surveillance Study. The certified athletic trainers of participating schools submitted athlete-exposure (AE) and injury information weekly. RESULTS: Participating schools reported 2900 football concussions during 3,528,790 AEs for an overall rate of 8.2 concussions per 10,000 AEs. Concussion rates significantly increased from 2008-2009 through 2012-2013 overall (P = .006) as well as in competition (P = .027) and practice (P = .023). Characteristics of concussed football players (ie, mean number of symptoms, specific concussion symptoms, symptom resolution time, and time until return to play) were similar among players wearing new helmets when compared with reconditioned helmets. Fewer players wearing an old/not reconditioned helmet had concussion symptoms resolve within 1 day compared with players wearing a new helmet. Despite differences in the manufacturers and models of helmets worn by all high school football players compared with players who sustained a concussion, the mean number of concussion symptoms, specific concussion symptoms, symptom resolution time, and time until return to play were similar for concussions sustained by football players wearing the most common helmet manufacturers and models. CONCLUSION: Overall, for new and reconditioned football helmets, the most common helmet manufacturers and models on the market today appear to provide high school football players with similar protection against concussions. CLINICAL RELEVANCE: Concussions can have serious acute and long-term effects. An understanding of concussion patterns in high school athletes can drive targeted preventive measures, including improvements to and/or better use of protective equipment, to reduce the incidence and/or severity of sports-related concussions. PMID- 26905507 TI - Antibiofilm action of a toluidine blue O-silver nanoparticle conjugate on Streptococcus mutans: a mechanism of type I photodynamic therapy. AB - The objective of this study was to evaluate the anti-biofilm efficacy of photodynamic therapy by conjugating a photosensitizer (TBO) with silver nanoparticles (AgNP). Streptococcus mutans was exposed to laser light (630 nm) for 70 s (9.1 J cm(-2)) in the presence of a toluidine blue O-silver nanoparticle conjugate (TBO-AgNP). The results showed a reduction in the viability of bacterial cells by 4 log10. The crystal violet assay, confocal laser scanning microscopy and scanning electron microscopy revealed that the TBO-AgNP conjugates inhibited biofilm formation, increased the uptake of propidium iodide and leakage of the cellular constituents, respectively. Fluorescence spectroscopic studies confirmed the generation of OH(*) as a major reactive oxygen species, indicating type I phototoxicity. Both the conjugates down-regulated the expression of biofilm related genes compared to TBO alone. Hence TBO-AgNP conjugates were found to be more phototoxic against S. mutans biofilm than TBO alone. PMID- 26905508 TI - [Speech delivered in the graduation ceremony of the residents of the class of 2014 of the Instituto Nacional de Cardiologia Ignacio Chavez]. PMID- 26905509 TI - "Buddy wire" technique in transcatheter aortic valve implantation with a balloon expandable valve: A rescue option in the setting of direct valve implantation (without predilation). PMID- 26905510 TI - [Variations between 2 ECG as predictors of atrial fibrillation: Cohort study]. AB - OBJETIVE: To evaluate the association between delta variations in the parameters of 2 sinusal ECG with atrial fibrillation (AF) onset. METHOD: Retrospective cohort of 9,975 adult patients and members of the prepaid system at Hospital Italiano de Buenos Aires from Argentina, who had at least 2 sinusal ECG between 2006 and 2011. Population was followed up for detection of AF. All measurements and electrocardiographic deltas (differences between the 2 ECG) were standardized. Hazard ratio (HR) was estimated for the development of AF for each delta of the different ECG parameters using a Cox regression model. RESULTS: During a median follow up of 3.5 years, 189 patients (1.89%) developed AF. Heart rate delta, ST interval delta and P wave amplitude were predictors of AF. Hazard ratio Adjusted for clinical characteristics and ECGbasal values was 0,86 (CI95%: 0.75-0.98, p=0.024) for heart rate delta, 1.12 (CI95%: 0.98-1.27, p=0.082) for ST interval delta and 1.21 (CI95%: 1.05-1.38, p=0.006) for P wave amplitude delta. CONCLUSION: Differences of heart rate and P wave amplitude between ECG's measurements may predict AF, independently of clinical features and ECGbasal values. PMID- 26905511 TI - Neutral, Anionic, and Cationic Manganese Dimers through Density Functional Theory. AB - The manganese dimer is the only first row transition metal dimer that presents an antiferromagnetic 1Sigmag + ground state bonded by a van der Waals interaction. The various density functional theory (DFT) investigations devoted to the study of the ground state of this molecule and of its anionic and cationic states, are usually based on the generalized gradient approximation, giving results which contradict the experimental observations. In this work, we describe the overall spectroscopic properties of the neutral, cationic and anionic manganese dimers with DFT, focusing on understanding the effects of the percentage of Hartree-Fock exchange and of the different exchange-correlation functionals, on the relative stability of the various potential energy curves. For each of the three species we classify the ferromagnetic and antiferromagnetic states, studying the vertical detachment energies, the ionization energies and the electron affinities. In this way, we locate a hybrid exchange-correlation functional able to give for all the three species, results comparable with the experimental measurements and with previous accurate multiconfigurational calculations, defining a more accurate density functional theory approach to study larger charged or neutral manganese clusters. PMID- 26905512 TI - Lung function decline over 25 years of follow-up among black and white adults in the ARIC study cohort. AB - BACKGROUND: Interpretation of longitudinal information about lung function decline from middle to older age has been limited by loss to follow-up that may be correlated with baseline lung function or the rate of decline. We conducted these analyses to estimate age-related decline in lung function across groups of race, sex, and smoking status while accounting for dropout from the Atherosclerosis Risk in Communities Study. METHODS: We analyzed data from 13,896 black and white participants, aged 45-64 years at the 1987-1989 baseline clinical examination. Using spirometry data collected at baseline and two follow-up visits, we estimated annual population-averaged mean changes in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) by race, sex, and smoking status using inverse-probability-weighted independence estimating equations conditioning-on-being-alive. RESULTS: Estimated rates of FEV1 decline estimated using inverse-probability-weighted independence estimating equations conditioning on being alive were higher among white than black participants at age 45 years (e.g., male never smokers: black: -29.5 ml/year; white: -51.9 ml/year), but higher among black than white participants by age 75 (black: -51.2 ml/year; white: -26). Observed differences by race were more pronounced among men than among women. By smoking status, FEV1 declines were larger among current than former or never smokers at age 45 across all categories of race and sex. By age 60, FEV1 decline was larger among former and never than current smokers. Estimated annual declines generated using unweighted generalized estimating equations were smaller for current smokers at younger ages in all four groups of race and sex compared with results from weighted analyses that accounted for attrition. CONCLUSIONS: Using methods accounting for dropout from an approximately 25-year health study, estimated rates of lung function decline varied by age, race, sex, and smoking status, with largest declines observed among current smokers at younger ages. PMID- 26905513 TI - Cutaneous lesions in sporadic angiosarcomas of the breast: a misleading presentation. AB - Primary angiosarcoma of the breast is a rare malignant tumour that presents in young women as a painless mass or a sensation of fullness in the breast. To report two cases of primary breast angiosarcoma presenting with unusual and misleading cutaneous lesions. A clinical investigation including ultrasound, MRI and histological examination. In the first patient, the lesion appeared as a superficial, acquired angioma; in the second as an indolent superficial haematoma. This type of primary presentation is exceptional and the benign appearance of the lesion, combined with a lack of breast mass, is misleading. The benign appearance and the pathological aspect of these lesions can lead to misdiagnosis. Comparison of clinical and pathological data is necessary to prevent delay in diagnosis. We believe that all acquired angiomatous lesions developing on the breasts of young women should raise suspicion of angiosarcoma. PMID- 26905514 TI - Reasons for Emergency Room Use Among U.S. Adults Aged 18-64: National Health Interview Survey, 2013 and 2014. AB - OBJECTIVE: This report examines the percentage of adults aged 18-64 who had an emergency room (ER) visit and their reasons for the most recent visit. METHODS: Using the 2013 and 2014 National Health Interview Survey, estimates of use in the past year and reasons for most recent ER visit are presented. A hierarchy was created to classify respondents' reasons for their last ER visit into three mutually exclusive categories: seriousness of the medical problem, doctor's office or clinic was not open, and lack of access to other providers. RESULTS: In 2014, 18% of adults visited the ER one or more times. Seriousness of the medical problem was the reason for the most recent ER visit for 77% of adults aged 18-64, 12% because their doctor's office was not open, and 7% because of a lack of access to other providers (4% did not select any reason). Percentages were similar in 2013. Controlling for other variables, adults with Medicaid were most likely to report that seriousness of the medical problem was the reason for the most recent ER visit. Adults with private coverage were most likely to have used the ER because the doctor's office was not open. Uninsured adults were more likely than adults with private coverage to have visited the ER because they lacked access to other providers. Differences in reasons for use between demographic groups were also identified. CONCLUSIONS: Few changes in ER use were noted between 2013 and 2014. Differences persist in ER use and reasons for ER use at most recent visit by insurance type as well as sociodemographic characteristics. PMID- 26905516 TI - Super Resolution Imaging of Nanoparticles Cellular Uptake and Trafficking. AB - Understanding the interaction between synthetic nanostructures and living cells is of crucial importance for the development of nanotechnology-based intracellular delivery systems. Fluorescence microscopy is one of the most widespread tools owing to its ability to image multiple colors in native conditions. However, due to the limited resolution, it is unsuitable to address individual diffraction-limited objects. Here we introduce a combination of super resolution microscopy and single-molecule data analysis to unveil the behavior of nanoparticles during their entry into mammalian cells. Two-color Stochastic Optical Reconstruction Microscopy (STORM) addresses the size and positioning of nanoparticles inside cells and probes their interaction with the cellular machineries at nanoscale resolution. Moreover, we develop image analysis tools to extract quantitative information about internalized particles from STORM images. To demonstrate the potential of our methodology, we extract previously inaccessible information by the direct visualization of the nanoparticle uptake mechanism and the intracellular tracking of nanoparticulate model antigens by dendritic cells. Finally, a direct comparison between STORM, confocal microscopy, and electron microscopy is presented, showing that STORM can provide novel and complementary information on nanoparticle cellular uptake. PMID- 26905517 TI - Drinking motives mediate emotion regulation difficulties and problem drinking in college students. AB - BACKGROUND: Problem drinking in college places students at an increased risk for a wealth of negative consequences including alcohol use disorders. Most research has shown that greater emotion regulation difficulties are related to increased problem drinking, and studies generally assume that drinking is motivated by efforts to cope with or enhance affective experiences. However, there is a lack of research specifically testing this assumption. OBJECTIVES: The current study sought to examine the mediating potential of drinking motives, specifically coping and enhancement, on the relationship between emotion regulation and problem drinking. METHOD: College participants (N = 200) completed an online survey, consisting of a battery of measures assessing alcohol use behaviors and related variables. RESULTS: Coping drinking motives fully mediated the emotion regulation/problem drinking relationship, and enhancement motives partially mediated this relationship. Exploratory analyses indicated that all four drinking motives (i.e. coping, enhancement, social, and conformity) simultaneously mediated the relationship between emotion regulation and quantity/frequency of alcohol use. However, only coping and enhancement significantly mediated the relationship between emotion regulation and alcohol-related consequences (e.g. alcohol dependence symptoms, alcohol-related injuries). CONCLUSION: The current results offer direction for potentially modifying brief alcohol interventions in efforts to reduce students' engagement in problem drinking behaviors. For example, interventions might incorporate information on the risks of using alcohol as a means of emotion regulation and offer alternative emotion regulation strategies. PMID- 26905515 TI - Fas/FasL, Bcl2 and Caspase-8 gene polymorphisms in Chinese patients with rheumatoid arthritis. AB - Apoptosis signals are necessary for maintaining homeostasis and an adequate immune response. Dysregulation of apoptosis-related genes in the immune system has an important impact on autoimmune diseases such as rheumatoid arthritis (RA). Thus, we investigated the association between Fas rs2234767 G/A, FasL rs763110 C/T, Bcl2 rs12454712 T/C, Bcl2 rs17757541 C/G, and Caspase-8 rs1035142 G/T polymorphisms and RA susceptibility in a Chinese population. These five single nucleotide polymorphisms (SNPs) were studied in a Chinese population consisting of 615 patients with RA and 839 controls. Genotyping was performed using a custom by-design 48-Plex SNP scan TM kit. Furthermore, we undertook a meta-analysis between FasL rs763110 C/T and RA. This study indicated that Fas rs2234767 and Bcl2 rs17757541 polymorphisms were risk factors for RA. No association was observed between FasL rs763110 C/T, Bcl2 rs12454712 T/C, and Caspase-8 rs1035142 G/T polymorphisms and RA in this study. The results of this meta-analysis suggested no significant association between FasL rs763110 C/T and RA. However, stratification analysis of this meta-analysis indicated that FasL rs763110 C/T increased the risk of Caucasian RA patients. In conclusion, this study demonstrated that Fas rs2234767 G/A and Bcl2 rs17757541 T/C polymorphisms might be associated with an increased risk of RA. This meta-analysis revealed that FasL rs763110 C/T was associated with an increased risk of Caucasian RA patients. PMID- 26905518 TI - Orbital two-channel Kondo effect in epitaxial ferromagnetic L1(0)-MnAl films. AB - The orbital two-channel Kondo effect displaying exotic non-Fermi liquid behaviour arises in the intricate scenario of two conduction electrons compensating a pseudo-spin-1/2 impurity of two-level system. Despite extensive efforts for several decades, no material system has been clearly identified to exhibit all three transport regimes characteristic of the two-channel Kondo effect in the same sample, leaving the interpretation of the experimental results a subject of debate. Here we present a transport study suggestive of a robust orbital two channel Kondo effect in epitaxial ferromagnetic L1(0)-MnAl films, as evidenced by a magnetic field-independent resistivity upturn with a clear transition from logarithmic- to square-root temperature dependence and deviation from it in three distinct temperature regimes. Our results also provide an experimental indication of the presence of two-channel Kondo physics in a ferromagnet, pointing to considerable robustness of the orbital two-channel Kondo effect even in the presence of spin polarization of the conduction electrons. PMID- 26905519 TI - Analyzing isolated blood vessel contraction in multi-well plates. AB - Organ baths have been successfully used for over a century to study the contractile or relaxation effects of drugs. Indeed, most of our understanding of vascular pharmacology is based on such in vitro studies. However, multiple parallel organ baths that require mechanical transduction consume relatively large amounts of drugs, gases, and buffers, and they take up a considerable bench space. In addition, such experiments have a high demand in terms of cost and animals, and the tissue preparation is labor intensive and slow. For these reasons, organ baths are no longer in the front line of industrial pharmacological research and they have almost disappeared from most academic laboratories. We have developed a very simple system, which can be implemented virtually in any laboratory, for the automatic analyses of rat aorta ring contraction based on optical methods and using multi-well plates. Rat aorta rings (~0.5 mm wide) were situated in 96-multi-well plates, and the luminal vessel areas were continuously monitored using a USB camera driven by newly developed algorithms. Liquids were handled using multichannel pipettes, although these procedures can be automated for drug screening. The concentration-response curves obtained were similar to those reported in the literature using traditional force transduction techniques on isolated tissues. This system can also be used with other tissue preparations and for simultaneous fluorescence measurements. The new system described here offers a simple, cheap, and reliable alternative to the classic organ bath system. PMID- 26905521 TI - MR-based assessment of body fat distribution and characteristics. AB - The assessment of body fat distribution and characteristics using magnetic resonance (MR) methods has recently gained significant attention as it further extends our pathophysiological understanding of diseases including obesity, metabolic syndrome, or type 2 diabetes mellitus, and allows more detailed insights into treatment response and effects of lifestyle interventions. Therefore, the purpose of this study was to review the current literature on MR based assessment of body fat distribution and characteristics. PubMed search was performed to identify relevant studies on the assessment of body fat distribution and characteristics using MR methods. T1-, T2-weighted MR Imaging (MRI), Magnetic Resonance Spectroscopy (MRS), and chemical shift-encoding based water-fat MRI have been successfully used for the assessment of body fat distribution and characteristics. The relationship of insulin resistance and serum lipids with abdominal adipose tissue (i.e. subcutaneous and visceral adipose tissue), liver, muscle, and bone marrow fat content have been extensively investigated and may help to understand the underlying pathophysiological mechanisms and the multifaceted obese phenotype. MR methods have also been used to monitor changes of body fat distribution and characteristics after interventions (e.g. diet or physical activity) and revealed distinct, adipose tissue-specific properties. Lastly, chemical shift-encoding based water-fat MRI can detect brown adipose tissue which is currently the focus of intense research as a potential treatment target for obesity. In conclusion, MR methods reliably allow the assessment of body fat distribution and characteristics. Irrespective of the promising findings based on these MR methods the clinical usefulness remains to be established. PMID- 26905520 TI - The miR-21/PTEN/Akt signaling pathway is involved in the anti-tumoral effects of zoledronic acid in human breast cancer cell lines. AB - Preclinical data indicate a direct anti-tumor effect of zoledronic acid (ZA) outside the skeleton, but its molecular mechanism is still not completely clarified. The aim of this study was to investigate the anti-cancer effects of ZA in human breast cancer cell lines, suggesting that they may in part be mediated via the miR-21/PTEN/Akt signaling pathway. The effect of ZA on cell viability was measured by MTT assay, and cell death induction was analyzed using either a double AO/EtBr staining and M30 ELISA assay. A Proteome Profiler Human Apoptosis Array was executed to evaluate the molecular basis of ZA-induced apoptosis. Cell cycle analysis was executed by flow cytometry. The effect of ZA on miR-21 expression was quantified by qRT-PCR, and the amount of PTEN protein and its targets were analyzed by Western blot. ZA inhibited cell growth in a concentration- and time-dependent manner, through the activation of cell death pathways and arrest of cell cycle progression. ZA downregulated the expression of miR-21, resulting in dephosphorilation of Akt and Bad and in a significant increase of p21 and p27 proteins expression. These results were observed also in MDA-MB-231 cells, commonly used as an experimental model of bone metastasis of breast cancer. This study revealed, for the first time, an involvement of the miR 21/PTEN/Akt signaling pathway in the mechanism of ZA anti-cancer actions in breast cancer cells. We would like to underline that this pathway is present both in the hormone responsive BC cell line (MCF-7) as well as in a triple negative cell line (MDA-MB-231). Taken together these results reinforce the use of ZA in clinical practice, suggesting the role of miR-21 as a possible mediator of its therapeutic efficacy. PMID- 26905522 TI - Listeria monocytogenes mutants defective in gallbladder replication represent safety-enhanced vaccine delivery platforms. AB - The Gram positive intracellular pathogen Listeria monocytogenes represents a promising vaccine or therapeutic DNA delivery vector that has been successfully administered to humans in clinical trials. However in generating Listeria mutants with therapeutic potential it is important to balance safety attenuation with efficacy. Here we show that L. monocytogenes mutants with a reduced capacity for murine gallbladder replication are capable of stimulating T cell responses in mice and protecting vaccinated animals from secondary challenge. Mutation of L. monocytogenes genes lmo2566 or lmo0598 resulted in significant attenuation in the murine model yet mutants retained a capacity for intracellular growth and stimulation of T cell responses against key Listeria epitopes (LLO91-99 and P60217-225). Importantly the mutants showed a reduced capacity for growth in the gallbladders of vaccinated mice as well as significantly reduced faecal shedding indicating that this approach generates live Listeria-based vector delivery systems with a reduced capacity for the spread of live genetically modified microorganisms into the natural environment. PMID- 26905523 TI - Antileishmanial and Cytotoxic Activity of Some Highly Oxidized Abietane Diterpenoids from the Bald Cypress, Taxodium distichum. AB - Two new compounds, namely, a para-benzoquinone ring-containing abietane (1) and a para-benzoquinone ring-containing 7,8-seco-abietane (2), and 14 other known highly oxidized abietane diterpenoids (3-16) were isolated from an extract prepared from the cones of Taxodium distichum, collected in central Ohio. The active subfraction from which all compounds isolated in this study were purified was tested in vivo using Leishmania donovani-infected mice and was found to dose dependently reduce the parasite burden in the murine livers after iv administration of this crude mixture at 5.6 and 11.1 mg/kg. The structures of 1 and 2 were established by detailed 1D- and 2D-NMR experiments, HRESIMS data, and electronic circular dichroism studies. Compounds 3 and 4 were each fully characterized spectroscopically and also isolated from a natural source for the first time. Compounds 2-16 were tested in vitro against L. donovani promastigotes and L. amazonensis intracellular amastigotes. Compound 2 was the most active against L. amazonensis amastigotes (IC50 = 1.4 MUM), and 10 was the most potent against L. donovani promastigotes (IC50 = 1.6 MUM). These compounds may be suggested for further studies such as in vivo experimentation either alone or in combination with other Taxodium isolates. PMID- 26905524 TI - Methionine synthase A2756G transition might be a risk factor for male infertility: Evidences from seven case-control studies. AB - Methionine synthase (MTR) has a crucial role in DNA synthesis and methylation reactions. The aim of this study was to investigate the association of the MTR A2756G polymorphism with idiopathic male infertility. Blood samples were collected from 217 idiopathic infertile- and 233 healthy-men, and MTR-A2756G genotyping was performed by PCR-RFLP. Meta-analysis was conducted by pooling our data with the data obtained from 6 previous studies. Also, the effects of this substitution on protein structure were evaluated by bioinformatics tools. Our study revealed the association of AG-genotype, GG-genotype, and G-allele with male infertility. Meta-analysis showed a significant association between A2756G transition and male infertility. In addition, structural analysis of the transition effect on protein revealed a significant influence on MTR function (with score: 38; expected accuracy: 66%). These findings suggest that the A2756G substitution might be a genetic risk factor and a potential biomarker for idiopathic male infertility. PMID- 26905526 TI - Delivery systems for Leishmania vaccine development. AB - Leishmaniasis is a neglected disease and is endemic in tropical and sub-tropical areas worldwide. Lifelong immunity after recovery indicates that vaccination could be a promising approach to overcome the disease. Although different antigens have been successfully tested against all clinical forms, none of them have been shown to fulfill the safety and efficiency requirements for human applications. Hence, strong vehicles are needed to carry antigens of interest and potentiate its presence in the body. So far, various live or chemical carriers have been applied to reinforce the immunological effects of ideal antigens. In the current review, the recent attempts in this field have been summarized. PMID- 26905527 TI - Celebrating the Accomplishments of Those Special Individuals Who Have Contributed Significantly to Our Profession: The Academy Honors. PMID- 26905525 TI - Oxidized plasma albumin promotes platelet-endothelial crosstalk and endothelial tissue factor expression. AB - Plasma advanced oxidation protein products (AOPPs), a class of pro-inflammatory pathogenic mediators, accumulate in subjects with chronic kidney disease. Whether AOPPs contribute to coagulation abnormalities, which are frequently seen in uremic patients, is unknown. Here we report that AOPPs activate platelets via a CD36-mediated signaling pathway. Activation of signaling pathways by AOPP platelet interaction resulted in the expression of several platelet activation markers and rapidly induced the expression of CD40 ligand, triggering platelet adhesion to endothelial cells and promoting endothelial tissue factor expression. AOPPs and serum tissue factor levels were considerably increased in end stage renal disease patients on hemodialysis and a significant correlation of AOPPs and serum tissue factor was found. Interestingly, serum levels of AOPPs and tissue factor were substantially lower in stable kidney transplant patients when compared with hemodialysis patients. Given that CD36 is known to transduce the effects of oxidized lipids into platelet hyperactivity, our findings reveal previously unknown pro-thrombotic activities of oxidized plasma albumin via a CD36 dependent pathway. PMID- 26905528 TI - Assessing Auditory Processing Abilities in Typically Developing School-Aged Children. AB - BACKGROUND: Large discrepancies exist in the literature regarding definition, diagnostic criteria, and appropriate assessment for auditory processing disorder (APD). Therefore, a battery of tests with normative data is needed. PURPOSE: The purpose of this study is to collect normative data on a variety of tests for APD on children aged 7-12 yr, and to examine effects of outside factors on test performance. RESEARCH DESIGN: Children aged 7-12 yr with normal hearing, speech and language abilities, cognition, and attention were recruited for participation in this normative data collection. STUDY SAMPLE: One hundred and forty-seven children were recruited using flyers and word of mouth. Of the participants recruited, 137 children qualified for the study. Participants attended schools located in areas that varied in terms of socioeconomic status, and resided in six different states. DATA COLLECTION AND ANALYSIS: Audiological testing included a hearing screening (15 dB HL from 250 to 8000 Hz), word recognition testing, tympanometry, ipsilateral and contralateral reflexes, and transient-evoked otoacoustic emissions. The language, nonverbal IQ, phonological processing, and attention skills of each participant were screened using the Clinical Evaluation of Language Fundamentals-4 Screener, Test of Nonverbal Intelligence, Comprehensive Test of Phonological Processing, and Integrated Visual and Auditory Continuous Performance Test, respectively. The behavioral APD battery included the following tests: Dichotic Digits Test, Frequency Pattern Test, Duration Pattern Test, Random Gap Detection Test, Compressed and Reverberated Words Test, Auditory Figure Ground (signal-to-noise ratio of +8 and +0), and Listening in Spatialized Noise-Sentences Test. Mean scores and standard deviations of each test were calculated, and analysis of variance tests were used to determine effects of factors such as gender, handedness, and birth history on each test. RESULTS: Normative data tables for the test battery were created for the following age groups: 7- and 8-yr-olds (n = 49), 9- and 10-yr-olds (n = 40), and 11- and 12-yr-olds (n = 48). No significant effects were seen for gender or handedness on any of the measures. CONCLUSIONS: The data collected in this study are appropriate for use in clinical diagnosis of APD. Use of a low-linguistically loaded core battery with the addition of more language-based tests, when language abilities are known, can provide a well-rounded picture of a child's auditory processing abilities. Screening for language, phonological processing, attention, and cognitive level can provide more information regarding a diagnosis of APD, determine appropriateness of the test battery for the individual child, and may assist with making recommendations or referrals. It is important to use a multidisciplinary approach in the diagnosis and treatment of APD due to the high likelihood of comorbidity with other language, learning, or attention deficits. Although children with other diagnoses may be tested for APD, it is important to establish previously made diagnoses before testing to aid in appropriate test selection and recommendations. PMID- 26905530 TI - The Effect of Contralateral Pure Tones on the Compound Action Potential in Humans: Efferent Tuning Curves. AB - BACKGROUND: The compound action potential (CAP) has been suggested in the literature as an alternative to otoacoustic emissions for evaluating the efferent auditory system. However, very few studies have examined efferent influence on auditory nerve potentials in humans. PURPOSE: This study examines the effects of presenting contralateral pure tones on the ipsilateral CAP onset and offset amplitudes as a potential clinical tool for the assessment of efferent auditory function. RESEARCH DESIGN: CAPs for 1- and 4-kHz tone pips (TPs) and clicks were recorded from 9, 9, and 8 participants, respectively. Contralateral tones were presented at levels ranging from 20 to 70 dB HL in 10-dB steps. The frequencies of the contralateral tones were 0.5, 1, 2 kHz for the 1-kHz TP CAP; 2, 4, 8 kHz for the 4-kHz TP CAP; and 0.5, 1, 2, 4, 8 kHz for the click CAP. DATA ANALYSIS: The CAP onset and offset amplitudes in all experimental conditions were analyzed and compared to the CAP amplitude without contralateral stimulation (i.e., baseline). RESULTS: Maximum suppression of 1-kHz TP CAP onset amplitude was obtained in seven out of nine participants by the 1-kHz contralateral pure tone at 40 dB HL. The 4-kHz TP CAP onset amplitude was maximally suppressed in eight out of nine participants by the 8-kHz contralateral pure tone at 30 dB HL. The click CAP offset amplitude was maximally suppressed in four out of eight participants by the 8-kHz contralateral tone presented at 40 dB HL. The 1- and 4 kHz TP CAP offset and click CAP onset amplitudes were not affected by contralateral stimulation. CONCLUSIONS: These results along with the previous studies may suggest that the efferent system is maximally stimulated by moderate signal-level tones (i.e., 30-40 dB HL), and that efferent activity is dependent on frequency cues of both the stimulus and suppressor tones. Other factors that might be affecting efferent influence on the CAP in humans such as sound duration, phase, bandwidth, and periodicity need to be further investigated. PMID- 26905529 TI - The Effects of Preprocessing Strategies for Pediatric Cochlear Implant Recipients. AB - BACKGROUND: Cochlear implants (CIs) have been shown to improve children's speech recognition over traditional amplification when severe-to-profound sensorineural hearing loss is present. Despite improvements, understanding speech at low-level intensities or in the presence of background noise remains difficult. In an effort to improve speech understanding in challenging environments, Cochlear Ltd. offers preprocessing strategies that apply various algorithms before mapping the signal to the internal array. Two of these strategies include Autosensitivity ControlTM (ASC) and Adaptive Dynamic Range Optimization (ADRO((r))). Based on the previous research, the manufacturer's default preprocessing strategy for pediatrics' everyday programs combines ASC + ADRO((r)). PURPOSE: The purpose of this study is to compare pediatric speech perception performance across various preprocessing strategies while applying a specific programming protocol using increased threshold levels to ensure access to very low-level sounds. RESEARCH DESIGN: This was a prospective, cross-sectional, observational study. Participants completed speech perception tasks in four preprocessing conditions: no preprocessing, ADRO((r)), ASC, and ASC + ADRO((r)). STUDY SAMPLE: Eleven pediatric Cochlear Ltd. CI users were recruited: six bilateral, one unilateral, and four bimodal. INTERVENTION: Four programs, with the participants' everyday map, were loaded into the processor with different preprocessing strategies applied in each of the four programs: no preprocessing, ADRO((r)), ASC, and ASC + ADRO((r)). DATA COLLECTION AND ANALYSIS: Participants repeated consonant-nucleus consonant (CNC) words presented at 50 and 70 dB SPL in quiet and Hearing in Noise Test (HINT) sentences presented adaptively with competing R-Space(TM) noise at 60 and 70 dB SPL. Each measure was completed as participants listened with each of the four preprocessing strategies listed above. Test order and conditions were randomized. A repeated-measures analysis of was used to compare each preprocessing strategy for the group. Critical differences were used to determine significant score differences between each preprocessing strategy for individual participants. RESULTS: For CNC words presented at 50 dB SPL, the group data revealed significantly better scores using ASC + ADRO((r)) compared to all other preprocessing conditions while ASC resulted in poorer scores compared to ADRO((r)) and ASC + ADRO((r)). Group data for HINT sentences presented in 70 dB SPL of R-Space(TM) noise revealed significantly improved scores using ASC and ASC + ADRO((r)) compared to no preprocessing, with ASC + ADRO((r)) scores being better than ADRO((r)) alone scores. Group data for CNC words presented at 70 dB SPL and adaptive HINT sentences presented in 60 dB SPL of R-Space(TM) noise showed no significant difference among conditions. Individual data showed that the preprocessing strategy yielding the best scores varied across measures and participants. CONCLUSIONS: Group data reveal an advantage with ASC + ADRO((r)) for speech perception presented at lower levels and in higher levels of background noise. Individual data revealed that the optimal preprocessing strategy varied among participants, indicating that a variety of preprocessing strategies should be explored for each CI user considering his or her performance in challenging listening environments. PMID- 26905531 TI - The Effects of FM and Hearing Aid Microphone Settings, FM Gain, and Ambient Noise Levels on SNR at the Tympanic Membrane. AB - BACKGROUND: Speech understanding in noise is challenging for individuals with hearing loss. Hearing aids (HAs) alone are typically unable to resolve these listening difficulties. Frequency modulation (FM) systems or other remote microphone accessories, coupled to HA, are intended to provide listeners with a good signal-to-noise ratio (SNR), thus improving signal audibility and speech understanding. PURPOSE: The goal of this study was to assess variables that influence SNR at the tympanic membrane (TM) when using a remote microphone/HA combination. We examined microphone setting, transmission system gain, and background noise levels using (1) mathematical computations to manipulate variables and observe the outcomes and (2) behavioral testing. RESEARCH DESIGN: This study used mathematical computations to estimate SNR at the TM and a mixed model experimental design to confirm a subset of the calculations. STUDY SAMPLE: Ten children with normal hearing (mean age, 13.7 yr) and ten adults with high frequency sensorineural hearing loss (mean age, 49.6 yr) participated. DATA COLLECTION AND ANALYSIS: Speech recognition thresholds were obtained using Bamford-Kowal-Bench sentences in the presence of noise. Participants used an FM system coupled to an HA in an FM-only and an FM + HA microphone condition. RESULTS: Better performance was observed in the FM-only compared to FM + HA condition with the overall amount of the FM-only advantage slightly larger than the mathematical calculations predicted. Further calculations demonstrated that (1) when using an FM-only microphone setting, the SNR at the TM is determined primarily by the SNR at the FM microphone; (2) when both HA and FM microphones are active, the SNR is determined by the highest level of the speech, which is typically at the FM microphone, and the highest level of noise at either the FM or HA microphone; (3) increasing FM gain has no impact on SNR in an FM-only condition; and (4) in an FM + HA condition, increasing FM gain improves SNR. The amount of improvement depends on noise levels at the FM and HA microphones. When the noise levels are similar at the two microphones, an improvement in SNR of ~2 dB is expected. Greater improvement is expected when the level of the noise at the FM microphone can be reduced relative to the level at the HA microphone. CONCLUSIONS: When using a remote microphone system coupled with a listener's HA, several variables influence SNR at the TM. Two variables that can be manipulated by programming of either or both devices are the microphone setting and gain setting. Mathematical calculations were used to determine the specific influence of and interactions between these variables and showed the importance of (1) managing noise levels to optimize SNR; and (2) counseling clients regarding optimal use of and realistic expectations from their system. This information is useful in the clinical management of persons with hearing loss, especially with the advent and affordability of wireless microphone accessories to assist listeners in background noise. PMID- 26905532 TI - Vestibular Assessment and Rehabilitation: Ten-Year Survey Trends of Audiologists' Opinions and Practice. AB - BACKGROUND: The past decade has yielded changes in the education and training of audiologists and technological advancements that have become widely available for clinical balance function testing. It is unclear if recent advancements in vestibular instrumentation or the transition to an AuD degree have affected audiologists' vestibular clinical practice or opinions. PURPOSE: The purpose of this study was to examine predominant opinions and practices for vestibular assessment (VA) and vestibular rehabilitation (VR) over the past decade and between master's- and AuD-level audiologists. METHOD: A 31-question survey was administered to audiologists via U.S. mail in 2003 (N = 7,500) and electronically in 2014 (N = 9,984) with a response rate of 12% and 10%, respectively. RESULTS: There was an increase in the number of audiologists providing vestibular services in the past decade. Most respondents agreed that audiologists were the most qualified professionals to conduct VA. Less than half of the surveyed audiologists felt that graduate training was adequate for VA. AuD-level audiologists were more satisfied with graduate training and felt more comfortable performing VA compared to master's-level audiologists. Few respondents agreed that audiologists were the most qualified professionals to conduct VR or that graduate training prepared them to conduct VR. The basic vestibular test battery was unchanged across surveys and included: calorics, smooth pursuit, saccades, search for spontaneous, positional, gaze and optokinetic nystagmus, Dix-Hallpike, case history, and hearing evaluation. There was a trend toward greater use of air (versus water) calorics, videonystagmography (versus electronystagmography), and additional tests of vestibular and balance function. CONCLUSIONS: VA is a growing specialty area in the field of audiology. Better training opportunities are needed to increase audiologists' knowledge and skills for providing vestibular services. The basic tests performed during VA have remained relatively unchanged over the past 10 yr. PMID- 26905533 TI - On Diagnostic Accuracy in Audiology: Central Site of Lesion and Central Auditory Processing Disorder Studies. AB - BACKGROUND: In the field of audiology a test protocol (index test) is used to determine the presence or absence of a target condition. The value of an index test rests in its diagnostic accuracy. Results from an index test must be verified through the use of a reference standard. The clinician and researcher should determine the quality and applicability of diagnostic accuracy studies. The Standards for Reporting of Diagnostic Accuracy (STARD) statement was published in response to the low quality of research conducted across many fields of study. It provides guidelines for the development and interpretation of diagnostic accuracy studies. PURPOSE: The primary purpose of this article is to assess the degree to which the main principles of diagnostic accuracy studies are used for the detection of central auditory nervous system lesions and a central auditory processing disorder (CAPD). The secondary purpose is to compare the design of these studies to select key guidelines from the STARD statement. The third purpose of this article is to present an argument against the reassignment of diagnostic accuracy values of a particular index test for one target condition (e.g., a central site of lesion) to a different target condition (e.g., a CAPD). RESULTS: A review of diagnostic accuracy literature on the detection of a central site of lesion reveals the use of a reference standard for the independent verification of the index test results. However, diagnostic accuracy studies involving index tests for the detection of a CAPD show that independent verification of index test results is nonexistent or at best questionable. CONCLUSION: For a particular index test, while the diagnostic accuracy for detection of a central site of lesion may have been determined appropriately, it is inappropriate to reassign these diagnostic accuracy values to a different diagnostic target such as a CAPD. PMID- 26905536 TI - Transparency in Biomedical Research: Beautiful Evidence. PMID- 26905534 TI - Erratum. AB - [This corrects the article DOI: 10.3766/jaaa.14102.]. PMID- 26905537 TI - Global Vision Impairment and Blindness Due to Uncorrected Refractive Error, 1990 2010. AB - The purpose of this systematic review was to estimate worldwide the number of people with moderate and severe visual impairment (MSVI; presenting visual acuity <6/18, >=3/60) or blindness (presenting visual acuity <3/60) due to uncorrected refractive error (URE), to estimate trends in prevalence from 1990 to 2010, and to analyze regional differences. The review focuses on uncorrected refractive error which is now the most common cause of avoidable visual impairment globally. : The systematic review of 14,908 relevant manuscripts from 1990 to 2010 using Medline, Embase, and WHOLIS yielded 243 high-quality, population-based cross sectional studies which informed a meta-analysis of trends by region. The results showed that in 2010, 6.8 million (95% confidence interval [CI]: 4.7-8.8 million) people were blind (7.9% increase from 1990) and 101.2 million (95% CI: 87.88 125.5 million) vision impaired due to URE (15% increase since 1990), while the global population increased by 30% (1990-2010). The all-age age-standardized prevalence of URE blindness decreased 33% from 0.2% (95% CI: 0.1-0.2%) in 1990 to 0.1% (95% CI: 0.1-0.1%) in 2010, whereas the prevalence of URE MSVI decreased 25% from 2.1% (95% CI: 1.6-2.4%) in 1990 to 1.5% (95% CI: 1.3-1.9%) in 2010. In 2010, URE contributed 20.9% (95% CI: 15.2-25.9%) of all blindness and 52.9% (95% CI: 47.2-57.3%) of all MSVI worldwide. The contribution of URE to all MSVI ranged from 44.2 to 48.1% in all regions except in South Asia which was at 65.4% (95% CI: 62-72%). : We conclude that in 2010, uncorrected refractive error continues as the leading cause of vision impairment and the second leading cause of blindness worldwide, affecting a total of 108 million people or 1 in 90 persons. PMID- 26905538 TI - Clinical Pearls. PMID- 26905540 TI - Controlled Donation After Circulatory Determination of Death. AB - Controlled donation after circulatory determination of death (cDCDD) concerns donation after withdrawal of life-sustaining therapy (W-LST). We examine the ethical issues raised by W-LST in the cDCDD context in the light of a review of cDCDD protocols and the ethical literature. Our analysis confirms that W-LST procedures vary considerably among cDCDD centers and that despite existing recommendations, the conflict of interest in the W-LST decision and process might be difficult to avoid, the process of W-LST might interfere with usual end-of life care, and there is a risk of hastening death. In order to ensure that the practice of W-LST meets already well-established ethical recommendations, we suggest that W-LST should be managed in the ICU by an ICU physician who has been part of the W-LST decision. Recommending extubation for W-LST, when this is not necessarily the preferred procedure, is inconsistent with the recommendation to follow usual W-LST protocol. As the risk of conflicts of interest in the decision of W-LST and in the process of W-LST exists, this should be acknowledged and disclosed. Finally, when cDCDD programs interfere with W-LST and end-of-life care, this should be transparently disclosed to the family, and specific informed consent is necessary. PMID- 26905541 TI - Quick Response Tracheotomy: A Novel Surgical Procedure. AB - Quick response tracheostomy (QRT) is a novel open surgical technique to emergently establish an airway. The method is simple; the skills necessary to perform this procedure are rapidly acquired; and it is expedient, minimally traumatic, and remarkably devoid of complications often encountered with percutaneous dilatational tracheotomies, including those complications seen with cricothyroidotomies. Unlike all other tracheotomies in which considerable blunt dissection is required, QRT avoids tissue crushing because sharp dissection alone is used to acquire surgical access to the trachea. The QRT does not entail inserting a guidewire into the trachea, a standard feature for percutaneous tracheal access; it avoids any risk of unintended laceration of the posterior tracheal wall and proximal subjacent esophagus. The technique averts tracheal ring fracture and tracheoesophageal fistula complications. The QRT has a uniquely low incidence of inducing hemorrhage, and it requires no steps that cause temporary tracheal occlusion and will therefore not facilitate hypoxia. The QRT contributes minimally to conditions favorable for generating subglottic stenosis, and the procedure is swiftly executed with very low probability for external tracheal placement of the tracheostomy tube. The QRT is not a blind procedure. No special instruments are required for its execution nor is concurrent tracheoscopy required at any stage while performing a QRT as is specified for percutaneous tracheotomies. PMID- 26905543 TI - The Search Continues for the Ideal Method to Localize Nonpalpable Breast Lesions. PMID- 26905542 TI - Impact of Obesity on Sentinel Lymph Node Mapping in Patients with Newly Diagnosed Uterine Cancer Undergoing Robotic Surgery. AB - PURPOSE: The aim of this study was to determine the impact of obesity on the rate of successful sentinel lymph node (SLN) mapping in patients with uterine cancer undergoing robotic surgery, and compare SLN detection rates using indocyanine green (ICG) versus blue dye. METHODS: We reviewed robotic cases undergoing SLN mapping with a cervical injection from January 2011 to December 2013 using either blue dye or ICG with near-infrared (NIR) fluorescence imaging. Data were stratified by body mass index (BMI) and the dye used. Appropriate statistical tests were applied. RESULTS: Overall, 472 cases were identified. Bilateral mapping was successful in 352 cases (75 %), and unilateral mapping was successful in 73 cases (15 %). Bilateral mapping was achieved in 266 (85 %) of 312 ICG cases compared with 86 (54 %) of 160 blue-dye cases (p < 0.001). Cases with successful bilateral mapping had a median BMI of 29.8 kg/m(2) (range 16.3-65.3 kg/m(2)); cases with no mapping had a median BMI of 34.7 kg/m(2) (range 21.4-60.4 kg/m(2)) (p = 0.001). With increasing BMI, there was a significant decrease in successful bilateral mapping rates for both the ICG (p < 0.001) and blue-dye groups (p = 0.041); however, the use of ICG resulted in better bilateral (p = 0.002) and overall (p = 0.011) mapping rates compared with the use of blue dye in all BMI groups. CONCLUSIONS: ICG results in a higher overall and bilateral SLN detection than blue dye in women with uterine cancer. Successful mapping decreases with increasing BMI irrespective of the dye used; however, it is significantly improved with the use of ICG and NIR fluorescence imaging compared with blue dye. PMID- 26905545 TI - Transient Elastographic Values of Healthy Volunteers in a Tertiary care Hospital. AB - INTRODUCTION: Transient elastography is a very promising noninvasive procedure to determine liver stiffness for diagnosis of fibrosis in various chronic liver diseases. However, studies on normal values of liver stiffness in apparently healthy subjects are still few. We aimed to determine liver stiffness values in healthy Nepalese volunteers. METHODS: Transient elastography (Fibro ScanR, Echosens, Paris, France) was performed to find out liver stiffness values in 45 apparently healthy volunteers after explaining study protocol. Complete medical examination with routine laboratory tests was performed. Subjects with normal liver biochemistries and normal liver ultrasonography were taken for analysis. RESULTS: Mean liver stiffness value of study subjects was 4.24 +/- 0.70 kPa. Liver stiffness value was found higher in males than in females (4.32+/-0.74 vs 4.07+/-0.61 kPa, respectively, P =0.26) but not statistically significant. Similarly, comparison between age and liver stiffness also showed positive correlation( r = 0.211) but not statistically significant( P = 0.164) CONCLUSIONS: Our study showed that the mean liver stiffness value was 4.24 +/- 0.70 kPa in our population and influence of age, gender and body mass index were not significant. PMID- 26905544 TI - The complete genome sequences of two naturally occurring recombinant isolates of Sugarcane mosaic virus from Iran. AB - Sugarcane mosaic virus (SCMV) is the most prevalent virus causing sugarcane mosaic and maize dwarf mosaic diseases. Here, we presented the first two complete genomic sequences of Iranian SCMV isolates, NRA and ZRA from sugarcane and maize. The complete genome sequences of NRA and ZRA were, respectively, 9571 and 9572 nucleotides (nt) in length, excluding the 3'-terminal poly(A) tail. Both isolates contained a 5'-untranslated region (UTR) of 149 nt, an open reading frame of 9192 nt encoding a polyprotein of 3063 amino acids (aa), and 3'-UTR of 230 nt for NRA and 231 nt for ZRA. SCMV-NRA and -ZRA genome nucleotide sequences were 97.3 % identical and shared nt identities of 79.1-92 % with those of other 21 SCMV isolates available in the GenBank, highest with the isolate Bris-A (AJ278405) (92 and 91.7 %) from Australia. When compared for separate genes, most of their genes shared the highest identities with Australian and Argentinean isolates. Phylogenetic analysis of the complete genomic sequences reveals that SCMV can be clustered to three groups. Both NRA and ZRA were clustered with sugarcane isolates from Australia and Argentina in group III but formed a separate sublineage. Recombination analysis showed that both isolates were intraspecific recombinants, and represented two novel recombination patterns of SCMV (in the P1 coding region). NRA had six recombination sites within the P1, HC-Pro, CI, NIa Vpg, and NIa-pro coding regions, while ZRA had four within the P1, HC-Pro, NIa Pro, and NIb coding regions. PMID- 26905546 TI - Emergency Peripartum Hysterectomy as Postpartum Hemorrhage Treatment: Incidence, Risk factors, and Complications. AB - INTRODUCTION: The aim of the research was to investigate incidence, risk factors, and complications associated with emergency peripartum hysterectomy, the ultimate treatment method for intractable postpartum hemorrhage. METHODS: This is a single center case-control study conducted in Chongqing city in central China from 1st January 2007 to 31st December 2012 for emergency peripartum hysterectomy performed as a treatment of postpartum hemorrhage both in caesarean and vaginal delivery cases. While the study group included emergency peripartum hysterectomy (n=61) due to intractable postpartum hemorrhage, the control group included no hysterectomy (n=333) during the same study period. RESULTS: We found 61 cases recorded for emergency peripartum hysterectomy for intractable postpartum hemorrhage. Incidence of peripartum hysterectomy was 2.2 per 1000 deliveries. Emergency peripartum hysterectomy as treatment of intractable postpartum hemorrhage include the followings: (i) blood loss 1000-2000 ml, crude odd ratio (OR) =18.48 (95% CI 5.1-65.7), adjusted odd ratio (AOR) = 9.1 (95% CI 2.2-37.7); (ii) blood loss >2000 ml, OR = 152 (95% CI 43.7-528.4), AOR = 45.3 (95% CI 11.6 176.9); (iii) previous caesarean section, OR = 5.5 (95% CI 2.9-9.7), AOR = 3.7(95% CI 1.4-9.9); (iv) uterine atony, OR = 11.9 (95% CI 5.8-24.6), AOR = 7.5 (95% CI 1.8-30.2); (v) placenta previa, OR = 2.04 (95% CI 1.1-3.5), AOR = none. CONCLUSIONS: Emergency peripartum hysterectomy is the last resort as treatment of intractable severe postpartum hemorrhage. Our study depicts that severe post partum hemorrhage, further dreaded complex events for emergency peripartum hysterectomy, has significant association with placental factors, previous caesarean section, and uterine atony. Pathologically, placenta accreta remained the most leading cause of hysterectomy. PMID- 26905547 TI - Socio-Demographic Correlates in Patients with First Episode Depression in a Tertiary Hospital. AB - INTRODUCTION: Depression is the most chronic mental illness that afflicts mankind. It is widely believed to be the disease affecting mainly female gender, economically disadvantaged group with low level of education and those residing in the urban setup. There are only few studies looking into the socio-demographic correlates of depression in the context of Nepal. METHODS: We looked at 70 patients with new-onset depression who met the criteria for diagnosis of depression as per ICD-10 DCR. A self- designed semi- structured proforma was developed to obtain the socio-demographic variables and was filled in the OPD and the data were analyzed. RESULTS: Mean age of the patients was 30.30+/-9.75 years and 70% of the patients were females. There were almost equal number of patients residing in and out of Kathmandu valley. Most of the patients had attained secondary level of education and were married, housewives and belonged to nuclear family. Majority were Hindus, Brahmins, and from middle class family. CONCLUSIONS: We found that patients with first episode depression were relatively young with female predominance most attaining at least secondary level of education; and most belonging to middle class nuclear families. PMID- 26905548 TI - Ondansetron and Granisetron for prevention of postoperative nausea and vomiting following laparoscopic cholecystectomy. AB - INTRODUCTION: Laparoscopic surgeries are known to be associated with a higher incidence of postoperative nausea and vomiting (PONV). Prophylaxis of PONV is usually achieved with a single-dose antiemetic drug administered during the surgical procedure. The aim of this study was to compare the antiemetic efficacy of two different 5-hydroxytryptamine-3 (5HT3) receptor antagonists, ondansetron and granisetron when given prophylactically to patients undergoing laparoscopic cholecystectomy. METHODS: It was a randomized, double blind study, conducted in 90 patients. Patients were divided into two groups: Group A and Group B with 45 patients in each group. Patients in groupA were given 100 microgram/kg ondansetron intravenously (IV), and patients in Group B were given 40 microgram/kg granisetron. Both the drugs were diluted in 10 ml of 0.9% NaCl and were given at the end of surgery. The standard general anesthetic technique was administered to all the patients. Episodes of nausea, retching and vomiting were assessed during the first 24 hours after anesthesia. RESULTS: There was no statistically significant difference for demographic data and duration of surgery among the two groups (P>0.05). Evaluated nausea and vomiting scores in the first 3 hours period revealed that each of the drugs had a similar antiemetic effect (P>0.05). Between 4-12 hours also the episodes of nausea, retching as well as vomiting were statistically insignificant in both the groups. In the last 12 hours, episodes of nausea, retching and vomiting were significantly higher in ondansetron group. CONCLUSIONS: Granisetron, when given prophylactically, resulted in a significantly lower incidence of PONV than ondansetron in the first 24 hours. PMID- 26905549 TI - Acute Viral Hepatitis in Pediatric Age Groups. AB - INTRODUCTION: Our clinical experience showed that there has been no decrease in pediatric cases of acute viral hepatitis in Kathmandu. The objective of the study was to analyze the etiology, clinical features, laboratory parameters, sonological findings and other to determine the probable prognostic factors of Acute Viral Hepatitis in pediatric population. METHODS: Consecutive patients of suspected Acute Viral Hepatitis, below the age of 15 years, attending the liver clinic between January 2006 and December 2010 were studied. After clinical examination they were subjected to blood tests and ultrasound examination of abdomen. The patients were divided in 3 age groups; 0-5, 5-10 and 5-15 years. Clinical features, laboratory parameters, ultrasound findings were compared in three age groups. RESULTS: Etiology of Acute Viral Hepatitis was Hepatitis A virus 266 (85%), Hepatitis E virus in 24 (8%), Hepatitis B virus in 15 (5%). In 7(2%) patients etiology was unknown. Three patients went to acute liver failure but improved with conservative treatment. There was no statistical difference in most of the parameters studied in different age groups. Ascites was more common in 5-10 years age group. Patients with secondary bacterial infection, ultrasound evidence of prominent biliary tree and ascites were associated with increased duration of illness. Patients with history of herbal medications had prolonged cholestasis. CONCLUSIONS: Hepatitis A is most common cause of Acute Viral Hepatitis in pediatric population. Improper use of herbal medications, secondary bacterial infection and faulty dietary intake was associated with prolonged illness. Patients with prominent biliary radicals should be treated with antibiotics even with normal blood counts for earlier recovery. PMID- 26905550 TI - Frequency of Blood Culture Isolates and their Antibiogram in a Teaching hospital. AB - INTRODUCTION: Bloodstream infections are associated with significant patient morbidity and mortality. Antimicrobial susceptibility patterns should guide the choice of empiric antimicrobial regimens for patients with bacteremia. METHODS: Blood sample received from the patient attending Nepal Medical College and Teaching Hospital from March, 2012 - August, 2012 were subjected to culture. Isolate identification and antimicrobial susceptibility testing was done by standard microbiological method. RESULTS: Out of the total 2,766 blood samples, 368 (13.3%) showed bacterial growth. The percentage of neonatal septicemia was 368 (13.3%). Staphylococcus aureus (28%) was the most common isolates followed by Salmonella enterica Serotype Typhi (22%), Coagulase negative Staphylococci (9.5%), Salmonella enterica Serotype Paratyphi ((7.6%) and Klebsiella pneumoniae (7.6%). 26.3% of the isolates of Staphylococcus aureus were oxacillin resistant. Most of the gram positive organisms were susceptible to amikacin and vancomycin and showed high level resistance to cefuroxime and cotrimoxazole. Out of 109 isolates of typhoid bacilli, 95.3% were resistant to nalidixic acid,79% to ciprofloxacin and 60.5% to ofloxacin. More than 50% of the isolates of Klebsiella pneumoniae and Escherichia coli showed resistance to cephalosporins and cotrimoxazole. Acinetobacter sp. showed high resistance (more than 60%) to ceftriaxone and ofloxacin. More than 20% of the isolates of Pseudomonas aeruginosa were resistant to ciprofloxacin and amikacin. CONCLUSIONS: Ongoing surveillance for antimicrobial susceptibility remains essential, and will enhance efforts to identify resistance and attempt to limit its spread. PMID- 26905551 TI - Psychiatric Comorbidities in Patients with Deliberate Self-Harm in a Tertiary Care Center. AB - INTRODUCTION: Deliberate self-harm (DSH) is one of the common psychiatric emergencies in medical practice. It has become a global health problem with rates increasing over time. Very few studies have been conducted on this important health issue in Nepal. We conducted a hospital based study to evaluate the cause, mode and psychiatric comorbidities present in patients of DSH. METHODS: This cross sectional study was performed on 200 cases of deliberate self-harm in a tertiary referral centre in Eastern Nepal from April 2012 to July 2012 by the data collected from the medical records of these patients. Various sociodemographic data and psychiatric comorbidities prevalent in them were studied. RESULTS: Most of the patients (77%) were below the age of 35. The female to-male ratio was 1.35:1. 76% of the patients had received formal education. Majority (73.5%) were married. By occupation, 38% were housewives and 25.5% were students. 72.5% of cases had consumed organophosphates/-chlorides. Interpersonal conflict (72%) was the major cause for DSH. Psychiatric disorders according to ICD-10 criteria were found in 37% of cases and premorbid personality problems were found in 20% of cases. The most prevalent psychiatric disorder was adjustment disorder (13.5%) followed by mood disorder (11%). CONCLUSION: Majority of DSH cases were of younger generation. Psychiatric disorders and comorbid personality problems were commonly seen in DSH patients. This has significance for proper evaluation and management. PMID- 26905552 TI - Percutaneous Adductor Release in Nonambulant Children with Cerebral Palsy. AB - INTRODUCTION: Adductor spasticity at hips is the main barrier in functional activities and rehabilitation of spastic cerebral palsy patients. The aim of this study is to evaluate the results of percutaneous adductor release under general anaesthesia. METHODS: From July 2005 to July 2010, 64 hips in 32 patients (19 males and 13 females) were recruited from outpatient department having adductor contracture at hips in cerebral palsy children. All children were operated under general anaesthesia. All children were followed for twenty-four months. The clinical results were evaluated radiologically, including measurement of CE- angle, AC-index and femoral head coverage and in terms of activity level of children. RESULTS: Of the thirty-two children, twenty-eight showed marked and immediate improvement. None of our children was functionally worse at follow-up. The CE-angle and femoral head coverage did not change significantly. The AC-index improved significantly (P = 0.01).The results were excellent in 12.5% children, good in 50%, fair in 25% and poor in 12.5%. CONCLUSIONS: Bilateral mini-invasive adductor release can be an effective treatment for children suffering from adductor contracture refractory to nonoperative management and early adductor release can prevent subluxation and possibly the need for future bony procedure on the proximal femur and pelvis. PMID- 26905553 TI - Kidney Biopsy: An Experience from Tertiary Hospital. AB - INTRODUCTION: Kidney Biopsy is an important diagnostic tool in Nephrology. It is useful in Nephrology in terms of diagnosis, prognosis and management. There is little information on renal biopsy data from central Nepal. We describe our center's experience in kidney biopsy in term of histological patterns, complications and outcomes. METHODS: We prospectively analyzed the biopsies data of patients over a period of one and half year. All kinds of kidney disease patients were included for kidney biopsy, irrespective of their clinical syndromes and underlying diagnosis. RESULTS: A total of 75 biopsies were analyzed. Majority of them were females; 42 (56%). Most of the biopsies; 63 (84%) were from younger subjects <= 45 years and majority of them fell in the age group 11-20 years. Most common clinical renal syndrome to undergo biopsy was Sub Nephrotic range Proteinuria in 40 (53.3%). Among comorbid conditions, 40 (53.3%) had Hypertension. The most common histological pattern seen was Mesangial proliferative Glomerulonephritis seen in 18 (24%). Among complications associated with the procedure, macroscopic hematuria was seen in 5 (6.7%) cases and clinically significant perinephric hematoma causing pain was seen in 4 (5.3%). There was no mortality associated with biopsy procedure. CONCLUSIONS: Sub Nephrotic range Proteinuria was the commonest clinical renal Syndrome observed. In terms of renal histology, Mesangial Proliferative Glomerulonephritis (MesPGN) was the commonest histological pattern observed. Kidney biopsy is a safe procedure without any significant adverse events. PMID- 26905554 TI - Maternal Death Reviews at a Tertiary Care Hospital. AB - INTRODUCTION: All pregnant women are at risk of obstetrical complications which occurs during labor and delivery that lead to maternal death. Here to report a 10 year review of maternal mortality ratio in "Paropakar Maternity and Women's Hospital (PMWH) Thapathali Kathmandu, Nepal. METHODS: Medical records of 66 maternal deaths were reviewed to study the likely cause of each death over the study period. RESULTS: There were a total of 66 maternal deaths. While 192487 deliveries conducted over the 10 year period. The maternal mortality ratio (MMR) was 356.64/100000 live birth. The highest MMR of 74.22/100,000 was observed in 2059 and lowest was 17.42/100,000 in 2068 B.S. Leading cause of MMR was remained hemorrhage accounting for 30.30% followed by eclampsia 24.24%. Sepsis, suspected cases of pulmonary embolism and amniotic fluid embolism each contributing 15.15%, 4.54% and 3.03% respectively. Where as anesthetic complication and abortion constitutes 6.06 % each equally for maternal death. The death noted in older women (30+year) were 36.36%. Primipara accounted for more deaths (51.51%). CONCLUSIONS: The fall in maternal mortality rate has been observed except for year 2063 BS. Hemorrhage is the main contributing cause behind maternal mortality. PMID- 26905555 TI - Management of Severe Pancreaticoduodenal Injuries. AB - Severe pancreaticoduodenal injuries are rare and no surgeon and institute get enough number of cases to acquire expertise. Hence, the management of such injuries remains controversial. We report a case of 28 years male who sustained a severe pancreaticoduodenal injury and was managed with emergency pancreaticoduodenectomy with immediate reconstruction. Various approaches have been described in literature with variable outcome. Damage control strategy seems to be most useful approach and major resection should be a part of debridement whenever required. Immediate reconstruction can be carried out safely if patients remain hemodynamically and metabolically stable. PMID- 26905556 TI - Molluscum Contagiosum Involving an Epidermoid Cyst - A Rare Association and Potential Source of Clinical Misdiagnosis. AB - Molluscum contagiosum (MC) is a viral infection of skin and mucous membrane commonly affecting the adolescents and young adults. Extensive lesions are usually common in immunocompromised patients. We herein report a rare case of molluscum contagiosum in an epidermoid cyst (EC) in a 24-year-old immunocompetent male. The provisional clinical diagnosis was inflammed epidermoid cyst or lipoma. On histopathological examination, the lesion displayed a unilocular epidermoid cyst in deep dermis, the lining of which was infected by molluscum contagiosum virus with characteristic inclusions. The overlying epidermis was absolutely normal having no attachment with the cyst. PMID- 26905557 TI - Malrotation of Intestine with Carcinoma Colon in Adult. AB - Malrotation of gut is a congenital anomaly and patients usually present in childhood. Occasionally it may present in adulthood. Patients are usually asymptomatic when malrotation of gut is detected during investigations or operation. Also, it can cause longstanding abdominal symptoms and volvulus of gut. Rarely malrotation of gut may present with gastrointestinal neoplasm. We present a 60 year old female with carcinoma caecum along with intestinal malrotation. PMID- 26905558 TI - Sepsis Causing Acquired Protein C and Protein S Deficiency. AB - Warfarin Induced Skin Necrosis is a well-known and dreaded complication in patients who is being started on warfarin without adequate bridging with other anticoagulants. The mechanism is thought to be due to protein C deficiency acquired after initial exposure to warfarin. We present a rather unusual cause of protein C deficiency due to sepsis resulting in warfarin induced skin necrosis. 43 year old lady who has been on chronic warfarin therapy secondary to anti phospholipid syndrome was admitted to the hospital for acute ischemic cerebellar stroke. Warfarin was held due to acute thrombocytopenia. She was discharged after restarting the warfarin. She presented back with septic shock due to pneumonia. She was found to have multiple necrotic areas consistent with skin necrosis. Unfortunately, patient died due to multi organ failure despite goal directed therapy. This case demonstrates the importance of recognizing the sepsis as an acquired cause of protein C deficiency. PMID- 26905559 TI - Surgical Management of Odontoid Fracture in Elderly. AB - Odontoid type II fractures are associated with high mortality in the elderly. No formal guidelines are present regarding the treatment of such fractures. Their management can be done either conservatively or surgically, however, surgical treatment is technically demanding and relatively new. We report a case of 75 years old man who presented to our clinical setting, following a history of fall. The CT scan and MRI showed odontoid type II fracture. With time, the neurological deficit got marked and he underwent transoral odontoidectomy and occipitocervical fixation using rods and screws via posterior approach. Patient's neurological condition improved dramatically and on the short term follow up, he had no motor deficit. Our experience suggests that occipitocervical fixation via posterior approach is a viable option for the management of odontoid type II fracture in the geriatric population. PMID- 26905560 TI - Sensitivity and Specificity of CT and Its signs for Diagnosis of Strangulation in Patients with Acute Small Bowel Obstruction. AB - INTRODUCTION: To perform a meta-analysis to review the sensitivity and specificity of computed tomography and different known computed yomography signs for the diagnosis of strangulation in patients with acute small bowel obstruction. METHODS: A comprehensive Pubmed search was performed for all reports that evaluated the use of CT and discussed different CT criteria for the diagnosis of acute SBO. Articles published in English language from January 1978 to June 2008 were included. Review articles, case reports, pictorial essays and articles without original data were excluded. The bivariate random effect model was used to obtain pooled sensitivity and pooled specificity. Summary receiver operating curve was calculated using Meta-Disc. Software Openbugs 3.0.3 was used to summarize the data. RESULTS: A total of 12 studies fulfilled the inclusion criteria. The pooled sensitivity and specificity of CT in the diagnosis of strangulation was 0.720 (95% CI 0.674 to 0.763) and 0.866 (95% CI 0.837 to 0.892) respectively. Among different CT signs, mesenteric edema had highest Pooled sensitivity of 0. 741 and lack of bowel wall enhancement had highest pooled specificity of 0.991. CONCLUSIONS: This review demonstrates that CT is highly sensitive as well as specific in the preoperative diagnosis of strangulation SBO which are in accordance with the published studies. Our analysis also shows that "presence of mesenteric fluid" is most sensitive, and "lack of bowel wall enhancement" is most specific CT sign of strangulation, and also justifies need of large scale prospective studies to validate the results obtained as well as to determine a clinical protocol. PMID- 26905561 TI - Intravenous Thrombolysis and Risk Factors for Ischemic Stroke. AB - Thrombolysis is one of the proven potential treatments for the management of acute ischemic stroke. Intravenous recombinant tissue-plasminogen activator (rt PA) is the only medically approved biological thrombolysing agent for the treatment of acute ischemic stroke within 4.5h of stroke (2.2% symptomatic intracerebral haemorrhage, 12.7% mortality and 58.0% functional independence), but following the guideline and criteria provided by National Institute of Neurological Disorder and Stroke (NINDS) and SITS (Safe Implementation of Thrombolysis in Stroke) studies. Nepal needs to evidently introduce intravenous rt-PA in its clinical setting for treatment of acute ischemic stroke, which has been approved for more than a decade ago in developed countries. Several modifiable and non-modifiable risk factors can affect the outcomes of the treatment with intravenous rt-PA. Early modification of factors predicting the risk outcomes can be a beneficial tool to justify the thrombolytic treatment. This review aims to discuss the major studies on thrombolysis using rt-PA and main factors that can affect the outcomes of treatment in ischemic stroke. PMID- 26905562 TI - Medical Humanities in Nepal: Present Scenario. AB - Humanities have an essential role in medical education. The current gap between the humanities and medicine has to be bridged and there should be continuous and vigorous debate about the theory and practice of medical humanities. Medical humanities is a relatively new concept even in developed countries, and is at infancy stage in developing countries. In Nepal, modules on medical humanities have been initiated in certain medical schools by enthusiastic faculties and it requires further debates for inclusion in curriculum. PMID- 26905563 TI - Transmitted HIV drug resistance-does the problem exists in Nepal ? PMID- 26905564 TI - The green peach aphid Myzus persicae perform better on pre-infested Chinese cabbage Brassica pekinensis by enhancing host plant nutritional quality. AB - The green peach aphid, Myzus persicae Sulzer, is a notorious pest on vegetables, which often aggregates in high densities on crop leaves. In this study, we investigated whether M. persicae could suppress the resistance level of Chinese cabbage Brassica pekinensis. M. persicae performed better in terms of weight gain (~33% increase) and population growth (~110% increase) when feeding on previously infested (pre-infested) Chinese cabbage compared with those on non-infested plants. However, when given a choice, 64% of the aphids preferred to settle on non-infested leaves, while 29% of aphids chose pre-infested leaves that had a 2.9 times higher concentration of glucosinolates. Aphid feeding significantly enhanced the amino acid:sugar ratio of phloem sap and the absolute amino acid concentration in plant leaves. Aphid infestation significantly increased the expression levels of salicylic acid (SA) marker genes, while it had marginal effects on the expression of jasmonate marker genes. Exogenously applied SA or methyl jasmonate had no significant effects on M. persicae performance, although these chemicals increased glucosinolates concentration in plant leaves. M. persicae infestation increase amino acid:sugar ratio and activate plant defenses, but aphid performed better on pre-infested plants, suggesting that both nutrition and toxics should be considered in insect-plant interaction. PMID- 26905565 TI - A double blind randomized active-controlled clinical trial on the intra-articular use of Md-Knee versus sodium hyaluronate in patients with knee osteoarthritis ("Joint"). AB - BACKGROUND: To evaluate the clinical outcomes of a group of patients affected by knee osteoarthritis (OA) treated with MD-Knee (Guna S.p.a., Milan, Italy) versus a group of patients treated with sodium hyaluronate. METHOD: This non-inferiority prospective randomized controlled trial involved 60 patients affected by knee OA, grade 2-3 of Kellgren-Lawrence scale. The MD-Knee Group, Group A (n = 29) was administered five intra-articular injections at 1 week interval; the sodium hyaluronate Group, Group B (n = 31), was administered five doses of intra articular injection of sodium hyaluronate at 1 week interval. All patients were prospectively evaluated before and at 3 and 6 months after the treatment by the Lequesne Knee Index (LKI) as primary endpoint and the Visual Analogue Scale (VAS), Pain Killer consumption and SF-36 questionnaires as secondary endpoints. RESULTS: At the 3- and 6 month follow-up, LKI and VAS improved significantly in both groups compared to baseline and no statistically significant differences were observed between Group A and Group B. There was no statistically significant difference in the SF36 questionnaire score and pain killer consumption between two groups at any time point. CONCLUSIONS: This study shows that both preparations exert similar clinical effects as assessed through multiple outcome measures. MD-Knee is effective on knee OA symptoms over 6 months after a 5-weekly injection course, and it is equally effective as the reference sodium hyaluronate. TRIAL REGISTRATION: TRIAL REGISTRATION NUMBER: ISRCTN93862496 . Registration date: January 18th, 2016. PMID- 26905567 TI - Validation of western blot for Histoplasma capsulatum antibody detection assay. AB - BACKGROUND: Histoplasmosis is worldwide systemic mycoses caused by the dimorphic fungus Histoplasma capsulatum. The isolation and identification of H. capsulatum in culture is the reference test for histoplasmosis diagnosis confirmation. However, in the absence of it, serology has been used as a presumptive diagnosis through antibody and antigen detection. The purpose of the present study was to validate an immunoassay method (western blot) for antibodies detection in the diagnosis of histoplasmosis. METHODS: To validate the western blot (WB) a study was conducted using 118 serum samples from patients with histoplasmosis and 118 serum controls collected from January 2000 to December 2013 in residents of the Rio de Janeiro State, Brazil. Diagnostic validation parameters were calculated based on the categorization of results obtained in a 2 * 2 table and subjected to statistical analysis. In addition, the viability of deglycosylated histoplasmin antigen (ptHMIN) onto nitrocellulose membranes previously sensitized was evaluated during the same period. RESULTS: The WB test showed sensitivity of 94.9 %, specificity of 94.1 %, positive predictive value of 94.1 %, negative predictive value of 94.9 %, accuracy of 94.5 %, and almost perfect precision. Besides, the strips have proved to be viable for using at least 5 years after ptHMIN antigen sensitization. CONCLUSION: Western blot test using ptHMIN provides sensitive, specific, and faster results. Therefore, could be considered a useful tool in the diagnosis of histoplasmosis being used by public health system, even in situations where laboratory facilities are relatively limited. PMID- 26905568 TI - Update on host-pathogen interactions in cystic fibrosis lung disease. AB - Bacterial and fungal infections are hallmarks of cystic fibrosis (CF) lung disease. In the era of long-term inhaled antibiotics and increasing CF patient survival, new "emerging" pathogens are detected in CF airways, yet their pathophysiological disease relevance remains largely controversial and incompletely defined. As a response to chronic microbial triggers, innate immune cells, particularly neutrophils, are continuously recruited into CF airways where they combat pathogens but also cause tissue injury through release of oxidants and proteases. The coordinated interplay between host immune cell activation and pathogens is essential for the outcome of CF lung disease. Here, we provide a concise overview and update on host-pathogen interactions in CF lung disease. PMID- 26905570 TI - A Meta-Analysis: Postoperative Pain Management in Colorectal Surgical Patients and the Effects on Length of Stay in an Enhanced Recovery After Surgery (ERAS) Setting. AB - INTRODUCTION: Enhanced Recovery After Surgery (ERAS) aims to minimize the length of a negative physiological response to surgical intervention. There are a number of aspects involved in ERAS protocols, one of which is postoperative pain relief. This meta-analysis investigates the current evidence for postoperative pain relief and its effect on patient pain and the length of stay after colorectal surgery. METHOD/RESULTS: Medline, PubMed, and EMBASE databases were searched for relevant studies between January 1966 and February 2016. All randomized controlled trials comparing postoperative pain management strategies in an ERAS setting with the length of stay as an outcome measure were selected. In addition to the length of stay, other outcomes analyzed were pain scores at 24 hours postoperatively, nausea, vomiting, and the time to the first bowel motion. RESULTS: There was a decrease in vomiting in the ERAS group compared with the control groups (relative risk=0.82; 95% confidence interval, 0.52-1.27). Mean differences in the length of stay (P=0.879), pain visual analogue scales (P=0.120), the time to the first bowel motion in hours (P=0.371), and nausea (P=0.083) were not statistically significant. CONCLUSIONS: In an ERAS setting with regard to a colorectal patient population, the choice of modality for postoperative pain relief does not impact the length of hospital stay, pain, the time to the first bowel motion, or nausea. PMID- 26905569 TI - Concomitant Migraine and Temporomandibular Disorders are Associated With Higher Heat Pain Hyperalgesia and Cephalic Cutaneous Allodynia. AB - OBJECTIVES: The aim of this study was to assess differences in the levels of hyperalgesia and cutaneous allodynia (CA) among women with migraine, temporomandibular disorders (TMD), or both. MATERIALS AND METHODS: Eighty women participated in the study. Mean ages for the control group, TMD group, migraine group, and migraine+TMD group were 26.15 (95% confidence interval [CI], 28.73 to 23.57), 31.65 (95% CI, 37.82 to 25.48), 35.05 (95% CI, 40.37 to 29.73), and 34.20 (95% CI, 37.99 to 30.41) years, respectively. The 12-item Allodynia Symptom Checklist was administered to assess CA. All participants underwent the Quantitative Sensory Test to determine the cold-pain and heat-pain thresholds. Mechanical pain thresholds were assessed using Semmes-Weinstein monofilaments. One-way analysis of variance and chi tests were used for statistical analysis. Alpha was set at 0.05 level for statistical significance. RESULTS: For all sites evaluated, the mean cold-pain threshold values were significantly lower in the TMD, migraine, and TMD+migraine groups compared with the control group. However, the mean heat-pain threshold values in the extracephalic region were significantly smaller only for the TMD+migraine group compared with the control group (41.94 degrees C; 95% CI, 40.54 to 43.34 vs. 44.79 degrees C; 95% CI, 43.45 to 46.12; P=0.03). Mechanical hyperalgesia in orofacial and neck sites was significantly lower in the TMD and TMD+migraine groups compared with the control group. Mean total 12-item Allodynia Symptom Checklist score in the TMD+migraine group was significantly higher than in the migraine group (9.53; 95% CI, 7.45 to 11.60 vs. 6.95; 95% CI, 5.35 to 8.55; P=0.02). CONCLUSIONS: More pronounced levels of hyperalgesia and CA were found in patients with both TMD and migraine. Thus, it is suggested that the concomitant presence of TMD and migraine may be related to intensification of central sensitization. PMID- 26905571 TI - Pain is Associated With Poorer Grades, Reduced Emotional Well-Being, and Attention Problems in Adolescents. AB - OBJECTIVES: The purpose of the present study was to determine whether pain is associated with specific aspects of academic performance, that is, poorer grades, and with factors critical to an adolescent's academic performance, that is, decreased emotional well-being and attention problems. We hypothesized that the association between pain and school grades is mediated by emotional well-being and attention problems. METHODS: In a cross-sectional study, we collected data from 2215 pupils, ages 12 to 13 years. Pain (no, occasional, and frequent), emotional well-being, and attention problems were measured with self-rating scales. Dutch, English, and math grades were taken as an index of academic performance. RESULTS: Frequent pain in adolescents was associated with poorer grades (Dutch P=0.02 and math P=0.01). Both occasional and frequent pain were associated with reduced emotional well-being (P<0.001) and reduced self-reported attention (P<0.001). However, the association between pain and lower grades disappeared when controlling for emotional well-being and attention. DISCUSSION: The present study shows that the association between pain and Dutch adolescents grades is mediated by reduced emotional well-being and attention problems. The association between pain and math grades is mediated by emotional problems. The results suggest that an intervention targeted at pain in adolescents could have a positive effect on their emotional well-being, attention, and school performance. PMID- 26905572 TI - Suicidal Ideation in Adolescents With and Without Chronic Pain. AB - OBJECTIVES: Suicidal ideation (SI) is common during adolescence and may have lethal outcomes. Despite evidence of the high prevalence and impact of suicidality in adults with chronic pain (CP), remarkably little is known about suicidality in adolescents with CP. This study aimed to examine the rates and characteristics of SI in a clinical sample of adolescents with CP compared with youth without CP. We also examined the relationship between pain-related and psychosocial factors and SI in youth. MATERIALS AND METHODS: Adolescents with (n=95) and without CP (n=91) completed self-reports of pain, functional disability, loneliness, family functioning, self-worth, and depressive symptoms including SI. RESULTS: Rates of SI were not different in youth with CP when compared with those without ((Equation is included in full-text article.), P>0.05). The content of suicidal thoughts also did not vary by group. Multivariate analysis showed an identical pattern of psychosocial correlates of SI in youth with and without CP; higher depressive symptoms and lower self-worth were associated with higher SI severity, controlling for demographics. Pain characteristics and functional disability were not significantly related to SI in youth with CP. DISCUSSION: Contrary to hypotheses and past findings in adults with CP, adolescents with CP did not endorse SI more frequently than peers without CP. Several psychosocial correlates were significantly associated with SI severity in our sample. Findings from this study serve as a foundation for future research on SI and associated risk factors in this population. PMID- 26905573 TI - Systematic review on the effectiveness of augmented reality applications in medical training. AB - BACKGROUND: Computer-based applications are increasingly used to support the training of medical professionals. Augmented reality applications (ARAs) render an interactive virtual layer on top of reality. The use of ARAs is of real interest to medical education because they blend digital elements with the physical learning environment. This will result in new educational opportunities. The aim of this systematic review is to investigate to which extent augmented reality applications are currently used to validly support medical professionals training. METHODS: PubMed, Embase, INSPEC and PsychInfo were searched using predefined inclusion criteria for relevant articles up to August 2015. All study types were considered eligible. Articles concerning AR applications used to train or educate medical professionals were evaluated. RESULTS: Twenty-seven studies were found relevant, describing a total of seven augmented reality applications. Applications were assigned to three different categories. The first category is directed toward laparoscopic surgical training, the second category toward mixed reality training of neurosurgical procedures and the third category toward training echocardiography. Statistical pooling of data could not be performed due to heterogeneity of study designs. Face-, construct- and concurrent validity was proven for two applications directed at laparoscopic training, face- and construct validity for neurosurgical procedures and face-, content- and construct validity in echocardiography training. In the literature, none of the ARAs completed a full validation process for the purpose of use. CONCLUSION: Augmented reality applications that support blended learning in medical training have gained public and scientific interest. In order to be of value, applications must be able to transfer information to the user. Although promising, the literature to date is lacking to support such evidence. PMID- 26905574 TI - Combination of etoricoxib and low-pressure pneumoperitoneum versus standard treatment for the management of pain after laparoscopic cholecystectomy: a randomized controlled trial. AB - BACKGROUND AND OBJECTIVES: Postoperative pain is one of the significant problems in laparoscopic surgery, especially during the first 6-12 h. This randomized controlled trial aimed to investigate the effect of combined preemptive etoricoxib 120 mg and low-pressure pneumoperitoneum for the management of pain after laparoscopic cholecystectomy (LC). PATIENTS AND METHODS: One hundred and twenty patients aged 18-75 with American Society of Anesthesiologists class I-II who were candidates for elective LC were recruited into the study. The patients were randomly divided into two groups, by 'block of four' randomization. The treatment group received preemptive etoricoxib 120 mg and intraabdominal pressure of 7 mmHg, and the control group received placebo and intraabdominal pressure of 14 mmHg. The postoperative pain score at rest was recorded utilizing a numeric rating scale at 1, 2, 6, 10, 14, 18, 22, and 24 h. Pain on movement/ambulation (cough) was also recorded at 6, 10, 14, 18, 22, and 24 h. RESULTS: There were no significant differences in the baseline characteristics of the two groups. The pain scores of the treatment versus control group of abdominal pain and incisional pain were significant on movement. Abdominal pain scores of the treatment group were decreased 0.98 when compared with the control group (p = 0.017), and incisional pain scores were also decreased 0.99 (p = 0.001). The incidences of postoperative shoulder/back pain were statistically significant: 41.8 % vs. 66.7 % in the treatment and control group, respectively (p = 0.009). The postoperative hospital stay in the treatment group and control group was: 1 day = 96.4 and 75.0 %, >1 day = 3.6 and 25.0 %, respectively (p = 0.001). CONCLUSIONS: A combination of preemptive etoricoxib and low-pressure pneumoperitoneum had significant effects in decreasing overall pain and the incidence of shoulder/back pain after LC and also shortened the hospital stay. CLINICAL TRIALS REGISTRATION NUMBER: TCTR20140213001. PMID- 26905575 TI - Design and validation of a cost-effective physical endoscopic simulator for fundamentals of endoscopic surgery training. AB - BACKGROUND: The American Board of Surgery will require graduating surgical residents to achieve proficiency in endoscopy. Surgical simulation can help residents to prepare for this proficiency test, accelerate skill acquisition, shorten the learning, and improve patient safety. Currently, endoscopic simulators are extremely cost-prohibitive. We therefore designed an inexpensive physical endoscopic simulator to (1) facilitate Fundamentals of Endoscopic Surgery skills training and (2) teach basic colonoscopy skills, for <$200.00. METHODS: We constructed the Rutgers Open Source Colonoscopy Simulator (ROSCO) from easily acquired commercial materials. For construct validation, we compared novices to experts in a two-arm non-randomized study. Each participant performed the five tasks and a full cecal intubation on the simulator. Face and content validity surveys were taken by the experts, after the construct validity study to determine the simulator's ability to achieve the intended task with "realism." Data were collected on (1) cost and construction, (2) time to completion of individual tasks, (3) percentage of task completion, and (4) survey statistics. RESULTS: Our simulator requires no advanced expertise, costs $62.77 US, and weighs 8.5 pounds. The ROSCO simulator was clearly able to distinguish expert from novice. Expert task times for completing all five tasks, performing the loop reduction, and reaching the splenic and hepatic flexures on the simulator were significantly better than novice times (p < 0.05). All participants were able to complete all five tasks on the simulator 100 % of the time. Three out of five experts "Agreed" or "Strongly Agreed" with five out of the six statements regarding the simulator's teaching ability. Four out of five experts rated each of the five specific aspects of the simulator as "Realistic" or "Very Realistic." CONCLUSIONS: We have designed a low-cost colonoscopy simulator with easily available materials and which requires very little advanced construction expertise and have demonstrated construct, face, and content validity. We believe this will have broad impact for endoscopic simulation, surgical education, and health education cost. PMID- 26905576 TI - Does the addition of fundoplication to repair the intra-thoracic stomach improve quality of life? AB - BACKGROUND: The role of fundoplication in addition to hiatal hernia repair has been controversial. The aim of this study was to compare quality of life related to gastroesophageal reflux disease (GERD) in patients who underwent intra thoracic stomach repair with and without fundoplication. We proposed that the group without a fundoplication would have poorer quality of life due to continued symptoms. METHODS: All patients undergoing foregut surgery at the Creighton University Esophageal Center are entered in a prospectively maintained database. The database was queried to identify patients who underwent surgery for a near complete (>75 % of stomach in chest) intra-thoracic stomach with gastric volvulus between 2004 and 2013. A questionnaire was derived from the Quality of Life in Reflux and Dyspepsia and Frequency Scale for Symptoms of GERD questionnaires to assess for symptoms related to reflux, and this questionnaire was administered by phone. RESULTS: A total of 150 patients underwent repair of ITS during the study period. A total of 109 patients had ITS repair with fundoplication, while 41 had only ITS repair. Follow-up was available in 54 % of patients in the fundoplication group (median follow-up of 5.2 years) and in 49 % of patients in the non-fundoplication group (median follow-up of 4 years). Significantly, more patients woke up at night (p < 0.01) and found themselves coughing around mealtime (p < 0.01) in the fundoplication group. Patients in the non fundoplication group had significantly more daytime reflux (p = 0.02). Despite these symptoms, only one patient in the fundoplication group and no patients in the non-fundoplication group admitted that these symptoms were severe enough to severely affect their quality of life. All other patients contacted felt satisfied, and >80 % rated their quality of life as either good or excellent. CONCLUSIONS: We conclude that there is not a significant difference in quality-of life parameters on long-term follow-up between patients undergoing ITS repair with or without fundoplication. PMID- 26905577 TI - Nationwide implementation of laparoscopic surgery for colon cancer: short-term outcomes and long-term survival in a population-based cohort. AB - BACKGROUND: Randomized trials show similar outcomes after open surgery and laparoscopy for colon cancer, and confirmation of outcomes after implementation in routine practice is important. While some studies have reported long-term outcomes after laparoscopic surgery from single institutions, data from large patient cohorts are sparse. We investigated short- and long-term outcomes of laparoscopic and open surgery for treating colon cancer in a large national cohort. METHODS: We retrieved data from the Norwegian Colorectal Cancer Registry for all colon cancer resections performed in 2007-2010. Five-year relative survival rates following laparoscopic and open surgeries were calculated, including excess mortality rates associated with potential predictors of death. RESULTS: Among 8707 patients with colon cancer that underwent major resections, 16 % and 36 % received laparoscopic procedures in 2007 and 2010, respectively. Laparoscopic procedures were most common in elective surgeries for treating stages I-III, right colon, or sigmoid tumours. The conversion rate of laparoscopic procedures was 14.5 %. Among all patients, laparoscopy provided higher 5-year relative survival rates (70 %) than open surgery (62 %) (P = 0.040), but among the largest group of patients electively treated for stages I III disease, the approaches provided similar relative survival rates (78 vs. 81 %; P = 0.535). Excess mortality at 2 years post-surgery was lower after laparoscopy than after open surgery (excess hazard ratio, 0.7; P = 0.013), but similar between groups during the last 3 years of follow-up. Major predictors of death were stage IV disease, tumour class pN+, age > 80 years, and emergency procedures (excess hazard ratios were 5.3, 2.4, 2.1, and 2.0, respectively; P < 0.001). CONCLUSION: Nationwide implementation of laparoscopic colectomy for colon cancer was safe and achieved results comparable to those from previous randomized trials. PMID- 26905579 TI - Predicting Personality Disorder Functioning Styles by the Five-Factor Nonverbal Personality Questionnaire in Healthy Volunteers and Personality Disorder Patients. AB - BACKGROUND: Detecting personality disorders in the illiterate population is a challenge, but nonverbal tools measuring personality traits such as the Five Factor Nonverbal Personality Questionnaire (FFNPQ) might help. We hypothesized that FFNPQ traits are associated with personality disorder functioning styles in a predictable way, especially in a sample of personality disorder patients. METHODS: We therefore invited 106 personality disorder patients and 205 healthy volunteers to answer the FFNPQ and the Parker Personality Measure (PERM) which measures 11 personality disorder functioning styles. RESULTS: Patients scored significantly higher on the FFNPQ neuroticism and conscientiousness traits and all 11 PERM styles. In both groups, the 5 FFNPQ traits displayed extensive associations with the 11 PERM styles, respectively, and the associations were more specific in patients. Associations between neuroticism, extraversion and agreeableness traits and most PERM styles were less exclusive, but conscientiousness was associated with antisocial (-) and obsessive-compulsive styles, and openness to experience with schizotypal and dependent (-) styles. CONCLUSIONS: Our study has demonstrated correlations between FFNPQ traits and PERM styles, and implies the nonverbal measure of personality traits is capable of aiding the diagnoses of personality disorders in the illiterate population. Enlarging sample size and including the illiterate might make for more stable results. PMID- 26905578 TI - Systematic review with meta-analysis of studies comparing single-incision laparoscopic colectomy and multiport laparoscopic colectomy. AB - BACKGROUND: There is currently a paucity of research comparing the clinical outcomes of single-incision laparoscopic colectomy (SILC) with those obtained with multiport laparoscopic colectomy (MLC). This meta-analysis aimed to examine whether SILC shows real benefits over MLC, especially in terms of feasibility, safety, and oncological adequacy. METHODS: A literature review of studies comparing SILC and MLC has been performed which looked at the following outcomes: mortality, morbidity, and oncological parameters of adequacy, as well as other potential benefits and drawbacks. Standardized mean difference for continuous variables and odds ratios for qualitative variables were calculated. RESULTS: Thirty studies comparing SILC and MLC were reviewed: two prospective randomized clinical trials (RCTs), eight prospective studies, and 20 retrospective comparative observational studies. Overall, in a cohort of 3502 patients who underwent surgery, SILC was used in 1068 cases (30.5 %) and MLC was used in 2434 cases (69.5 %). Mean intraoperative blood loss was significantly lower when the SILC procedure had been used (75.06 vs. 91.45 ml, P = 0.03); bowel function recovered significantly earlier in the SILC patients (1.96 vs. 2.15 days, P = 0.03); mean postoperative hospital stay was significantly shorter in the SILC group (5.55 vs. 6.60 days, P = 0.0005); and length of skin incision was significantly shorter in SILC patients (3.98 vs. 5.28 cm, P = 0.01). However, in the latter four outcomes, evidence of heterogeneity was found. In contrast, MLC showed significantly better results when compared to SILC in terms of distal free margins (12.26 vs. 10.98 cm, P = 0.01). CONCLUSIONS: SILC could be considered as a safe and feasible alternative to MLC in experienced hands. Further evidence for this surgical procedure should be assessed in the form of high-quality RCTs, with additional focus on its use in low rectal cancer resection. PMID- 26905580 TI - Is sutureless thyroid surgery safe in the hands of surgical trainees. A single centre retrospective study. AB - BACKGROUND: The safety and efficacy of sutureless thyroid surgery have been confirmed in many series. Equally, surgical expertise has been shown to influence postoperative outcome. This study aimed at investigating the safety of sutureless thyroid surgery in the hands of surgical trainees and to find out if this technique could be safely integrated into endocrine surgical training programs. METHODS: A single center retrospective comparison of the outcome of surgeries performed by experienced surgical attendings and trainees was performed. The LigaSure Precise was used in all cases. RESULTS: Two hundred and eight patients were included. The trainee group comprised of 61 cases managed by surgical trainees. Surgery was performed by surgical attendings in 147 cases (consultant group). The incidences of transient and permanent hypocalcaemia were 20.7 and 0.9% respectively, the corresponding values for recurrent nerve injury were 6.3 and 0.9%. Postoperative bleeding occurred in 3.4%. There was no difference amongst both groups with regard to postoperative outcome (p > 0.05). CONCLUSIONS: While sutureless thyroid surgery was safely performed by surgical trainees without relevant increase in perioperative complications in our department, further larger scale studies would be needed to confirm this would be the case more widely. PMID- 26905581 TI - Uncovering heart failure with preserved ejection fraction in patients with type 2 diabetes in primary care: time for a change. AB - Undetected heart failure appears to be an important health problem in patients with type 2 diabetes and aged >= 60 years. The prevalence of previously unknown heart failure in these patients is high, steeply rises with age, and is overall higher in women than in men. The majority of the patients with newly detected heart failure have a preserved ejection fraction. A diagnostic algorithm to detect or exclude heart failure in these patients with variables from the medical files combined with items from history taking and physical examination provides a good to excellent accuracy. Annual screening appears to be cost-effective. Both unrecognised heart failure with reduced and with preserved ejection fraction were associated with a clinically relevant lower health status in patients with type 2 diabetes. Also the prognosis of these patients was worse than of those without heart failure. Existing disease-management programs for type 2 diabetes pay insufficient attention to early detection of cardiovascular diseases, including heart failure. We conclude that more attention is needed for detection of heart failure in older patients with type 2 diabetes. PMID- 26905582 TI - Manipulation of the gut microbiota using resistant starch is associated with protection against colitis-associated colorectal cancer in rats. AB - This study evaluated whether dietary resistant starch (RS) and green tea extract (GTE), which have anti-inflammatory and anticancer properties, protect against colitis-associated colorectal cancer (CAC) using a rat model, also investigated potential mechanisms of action of these agents including their effects on the gut microbiota. Rats were fed a control diet or diets containing 10% RS, 0.5% GTE or a combination of the two (RS + GTE). CAC was initiated with 2 weekly azoxymethane (AOM) injections (10mg/kg) followed by 2% dextran sodium sulphate in drinking water for 7 days after 2 weeks on diets. Rats were killed 20 weeks after the first AOM. Colon tissues and tumours were examined for histopathology by H&E, gene/protein expression by PCR and immunohistochemistry and digesta for analyses of fermentation products and microbiota populations. RS and RS + GTE (but not GTE) diets significantly (P< 0.05) decreased tumour multiplicity and adenocarcinoma formation, relative to the control diet. Effects of RS + GTE were not different from RS alone. RS diet caused significant shifts in microbial composition/diversity, with increases in Parabacteroides, Barnesiella, Ruminococcus, Marvinbryantia and Bifidobacterium as primary contributors to the shift. RS-containing diets increased short chain fatty acids (SCFA) and expression of the SCFA receptor GPR43 mRNA, and reduced inflammation (COX-2, NF kB, TNF-alpha and IL-1beta mRNA) and cell proliferation P< 0.05. GTE had no effect. This is the first study that demonstrates chemopreventive effects of RS (but not GTE) in a rodent CAC model, suggesting RS might have benefit to patients with ulcerative colitis who are at an increased risk of developing CRC. PMID- 26905583 TI - Integrin-linked kinase as a novel molecular switch of the IL-6-NF-kappaB signaling loop in breast cancer. AB - Substantial evidence has clearly demonstrated the role of the IL-6-NF-kappaB signaling loop in promoting aggressive phenotypes in breast cancer. However, the exact mechanism by which this inflammatory loop is regulated remains to be defined. Here, we report that integrin-linked kinase (ILK) acts as a molecular switch for this feedback loop. Specifically, we show that IL-6 induces ILK expression via E2F1 upregulation, which, in turn, activates NF-kappaB signaling to facilitate IL-6 production. shRNA-mediated knockdown or pharmacological inhibition of ILK disrupted this IL-6-NF-kappaB signaling loop, and blocked IL-6 induced cancer stem cells in vitro and estrogen-independent tumor growth in vivo Together, these findings establish ILK as an intermediary effector of the IL-6-NF kappaB feedback loop and a promising therapeutic target for breast cancer. PMID- 26905584 TI - Adolescent dietary patterns and premenopausal breast cancer incidence. AB - Mammary tissue experiences the highest rate of proliferation during adolescence representing a period of heightened susceptibility. Few prospective studies have examined adolescent diet and breast cancer, and none have examined dietary patterns. Thus, we examined the association between adolescent dietary patterns and a diet quality index, the Alternative Healthy Eating Index (AHEI), and breast cancer in the Nurses' Health Study II among those who completed a 124-item food frequency questionnaire about their high-school diet (HS-FFQ). Cox proportional hazards regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (95% CI). Among 45204 women who completed the HS-FFQ, 863 cases of premenopausal breast cancer and 614 cases of postmenopausal cancer were diagnosed. A marginal inverse association was observed between the 'prudent' dietary pattern, characterized by high intake of vegetables, fruits, legumes, fish and poultry, and premenopausal breast cancer. Women in fifth quintile had a multivariable adjusted HR (95% CI) of 0.84 (0.67-1.04) for premenopausal breast cancer (Ptrend= 0.07) compared with the first quintile. Scoring higher on the AHEI was borderline significantly associated with premenopausal breast cancer with a HR of 0.81 (0.64-1.01) for the fifth quintile (Ptrend= 0.08), and this association appeared to be stronger for estrogen receptor-negative/progesterone receptor-negative tumors. No association was observed between the 'Western' pattern or the 'fast-food' pattern. Results were similar for each of these patterns when both premenopausal and postmenopausal breast cancer were considered together. An overall healthy diet during adolescence, similar to the prudent dietary pattern or adherence to the AHEI, may contribute to reducing the risk of breast cancer. PMID- 26905585 TI - A functional polymorphism in lnc-LAMC2-1:1 confers risk of colorectal cancer by affecting miRNA binding. AB - Genome-wide association studies (GWASs) have identified multiple susceptibility loci of colorectal cancer (CRC), however, causative polymorphisms have not been fully elucidated. Long non-coding RNAs (lncRNAs) are a recently discovered class of non-protein coding RNAs that involved in a wide variety of biological processes. We hypothesized that single nucleotide polymorphisms (SNPs) in lncRNA may associate with the CRC risk by influencing lncRNA functions. To evaluate the effects of SNPs on CRC susceptibility in Chinese populations, we first screened out all potentially functional SNPs in exons of lncRNAs located in CRC susceptibility loci identified by GWAS. Eight SNPs were selected and genotyped in 875 CRC cases and 855 controls and replicated in an independent case-control study consisting of 768 CRC cases and 768 controls. Analyses showed that CG and GG genotypes of the rs2147578 were significantly associated with increased risk for CRC occurrence in both case-control studies [combined analysis OR = 1.29; 95% confidence interval (CI) = 1.11-1.51, P = 0.001] compared to the rs2147578 CC genotype. Bioinformatics analyses showed that rs2147578 is located in the transcript of lnc-LAMC2-1:1 and could influence the binding of lnc-LAMC2-1:1/miR 128-3p. Further luciferase reporter assays demonstrated that the construct with the risk rs2147578G allele had relatively high expression activity compared with that of the rs2147578C allele. Expression quantitative trait loci analyses also showed that rs2147578 is correlated with the expression of a well established oncogene LAMC2 (laminin subunit gamma 2). These findings indicated that rs2147578 in lnc-LAMC2-1:1 might be a genetic modifier for the development of CRC. PMID- 26905586 TI - The novel agent phospho-glycerol-ibuprofen-amide (MDC-330) inhibits glioblastoma growth in mice: an effect mediated by cyclin D1. AB - Given that glioblastoma multiforme (GBM) is associated with poor prognosis, new agents are urgently needed. We developed phospho-glycerol-ibuprofen-amide (PGIA), a novel ibuprofen derivative, and evaluated its safety and efficacy in preclinical models of GBM, and its mechanism of action using human GBM cells and animal tumor models. Furthermore, we explored whether formulating PGIA in polymeric nanoparticles could enhance its levels in the brain. PGIA was 3.7- to 5.1-fold more potent than ibuprofen in suppressing the growth of human GBM cell lines. PGIA 0.75* IC50 inhibited cell proliferation by 91 and 87% in human LN-229 and U87-MG GBM cells, respectively, and induced strong G1/S arrest.In vivo, compared with control, PGIA reduced U118-MG and U87-MG xenograft growth by 77 and 56%, respectively (P< 0.05), and was >2-fold more efficacious than ibuprofen. Normal human astrocytes were resistant to PGIA, indicating selectivity. Mechanistically, PGIA reduced cyclin D1 levels in a time- and concentration dependent manner in GBM cells and in xenografts. PGIA induced cyclin D1 degradation via the proteasome pathway and induced dephosphorylation of GSK3beta, which was required for cyclin D1 turnover. Furthermore, cyclin D1 overexpression rescued GBM cells from the cell growth inhibition by PGIA. Moreover, the formulation of PGIA in poly-(L)-lactic acid poly(ethylene glycol) polymeric nanoparticles improved its pharmacokinetics in mice, delivering PGIA to the brain. PGIA displays strong efficacy against GBM, crosses the blood-brain barrier when properly formulated, reaching the target tissue, and establishes cyclin D1 as an important molecular target. Thus, PGIA merits further evaluation as a potential therapeutic option for GBM. PMID- 26905587 TI - Pancreatic cancer: associations of inflammatory potential of diet, cigarette smoking and long-standing diabetes. AB - Epidemiologic studies show strong associations between pancreatic cancer (PC) and inflammatory stimuli or conditions such as cigarette smoking and diabetes, suggesting that inflammation may play a key role in PC. Studies of dietary patterns and cancer outcomes also suggest that diet might influence an individual's risk of PC by modulating inflammation. We therefore examined independent and joint associations between inflammatory potential of diet, cigarette smoking and long-standing (>=5 years) type II diabetes in relation to risk of PC. Analyses included data from 817 cases and 1756 controls. Inflammatory potential of diet was measured using the dietary inflammatory index (DII), calculated from dietary intake assessed via a 144-item food frequency questionnaire, and adjusted for energy intake. Information on smoking and diabetes were obtained via risk factor questionnaires. Associations were examined using multivariable-adjusted logistic regression. Higher DII scores, reflecting a more proinflammatory diet, were associated with increased risk of PC [odds ratio (OR)Quintile 5 versus 1 = 2.54, 95% confidence interval (CI) = 1.87-3.46, P trend < 0.0001]. Excess risk of PC also was observed among former (OR = 1.29, 95% CI = 1.07-1.54) and current (OR = 3.40, 95% CI = 2.28-5.07) smokers compared with never smokers, and among participants with long-standing diabetes (OR = 3.09, 95% CI = 2.02-4.72) compared with nondiabetics. Joint associations were observed for the combined effects of having greater than median DII score, and being a current smoker (OR = 4.79, 95% CI = 3.00-7.65) or having long-standing diabetes (OR = 6.03, 95% CI = 3.41-10.85). These findings suggest that a proinflammatory diet may act as cofactor with cigarette smoking and diabetes to increase risk of PC beyond the risk of any of these factors alone. PMID- 26905590 TI - PAQR3 enhances Twist1 degradation to suppress epithelial-mesenchymal transition and metastasis of gastric cancer cells. AB - Twist1 is an essential transcription factor required to initiate epithelial mesenchymal transition (EMT) and promote tumor metastasis. PAQR3 is a newly found tumor suppressor that is frequently downregulated in many types of human cancers. Downregulation of PAQR3 is associated with accelerated metastasis and poor prognosis of the patients with gastric cancers. In this study, we demonstrate that PAQR3 is actively involved in the degradation of Twist1 and whereby regulates EMT and metastasis of gastric cancer cells. PAQR3 overexpression reduces the protein level but not the mRNA level of Twist1. The protein stability and polyubiquitination of Twist1 are altered by PAQR3. PAQR3 forms a complex with Twist1 and BTRC, an E3 ubiquitin ligase. PAQR3 enhances the interaction between Twist1 and BTRC. Twist1 is mobilized from the nucleus to a proteasome-containing structure in the cytoplasm upon overexpression of PAQR3 and BTRC, which is required for PAQR3-induced degradation of Twist1. The Twist1 box domain of the Twist1 protein is required for the interaction of Twist1 with both PAQR3 and BTRC, indispensable for PAQR3-mediated degradation of Twist1. Both BTRC and Twist1 are required for the inhibitory effects of PAQR3 on migration and EMT phenotype of gastric cancers cells. Importantly, Twist1 is indispensable for the inhibitory effect of PAQR3 on metastasis of gastric cancer cells in vivo Collectively, these findings not only pinpoint that Twist1 mediates the modulatory function of PAQR3 on EMT and metastasis but also suggest that targeting Twist1 is a promising strategy to control metastasis of tumors with downregulation of PAQR3. PMID- 26905589 TI - Persistent effect of mTOR inhibition on preneoplastic foci progression and gene expression in a rat model of hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) is a heterogeneous disease in which tumor subtypes can be identified based on the presence of adult liver progenitor cells. Having previously identified the mTOR pathway as critical to progenitor cell proliferation in a model of liver injury, we investigated the temporal activation of mTOR signaling in a rat model of hepatic carcinogenesis. The model employed chemical carcinogens and partial hepatectomy to induce progenitor marker-positive HCC. Immunohistochemical staining for phosphorylated ribosomal protein S6 indicated robust mTOR complex 1 (mTORC1) activity in early preneoplastic lesions that peaked during the first week and waned over the subsequent 10 days. Continuous administration of rapamycin by subcutaneous pellet for 70 days markedly reduced the development of focal lesions, but resulted in activation of the PI3K signaling pathway. To test the hypothesis that early mTORC1 activation was critical to the development and progression of preneoplastic foci, we limited rapamycin administration to the 3-week period at the start of the protocol. Focal lesion burden was reduced to a degree indistinguishable from that seen with continuous administration. Short-term rapamycin did not result in the activation of PI3K or mTORC2 pathways. Microarray analysis revealed a persistent effect of short-term mTORC1 inhibition on gene expression that resulted in a genetic signature reminiscent of normal liver. We conclude that mTORC1 activation during the early stages of hepatic carcinogenesis may be critical due to the development of preneoplastic focal lesions in progenitor marker-positive HCC. mTORC1 inhibition may represent an effective chemopreventive strategy for this form of liver cancer. PMID- 26905588 TI - Polymorphisms of the centrosomal gene (FGFR1OP) and lung cancer risk: a meta analysis of 14,463 cases and 44,188 controls. AB - Centrosome abnormalities are often observed in premalignant lesions and in situ tumors and have been associated with aneuploidy and tumor development. We investigated the associations of 9354 single-nucleotide polymorphisms (SNPs) in 106 centrosomal genes with lung cancer risk by first using the summary data from six published genome-wide association studies (GWASs) of the Transdisciplinary Research in Cancer of the Lung (TRICL) (12,160 cases and 16 838 controls) and then conducted in silico replication in two additional independent lung cancer GWASs of Harvard University (984 cases and 970 controls) and deCODE (1319 cases and 26,380 controls). A total of 44 significant SNPs with false discovery rate (FDR) <= 0.05 were mapped to one novel gene FGFR1OP and two previously reported genes (TUBB and BRCA2). After combined the results from TRICL with those from Harvard and deCODE, the most significant association (P combined = 8.032 * 10( 6)) was with rs151606 within FGFR1OP. The rs151606 T>G was associated with an increased risk of lung cancer [odds ratio (OR) = 1.10, 95% confidence interval (95% CI) = 1.05-1.14]. Another significant tagSNP rs12212247 T>C (P combined = 9.589 * 10(-6)) was associated with a decreased risk of lung cancer (OR = 0.93, 95% CI = 0.90-0.96). Further in silico functional analyzes revealed that rs151606 might affect transcriptional regulation and result in decreased FGFR1OP expression (P trend = 0.022). The findings shed some new light on the role of centrosome abnormalities in the susceptibility to lung carcinogenesis. PMID- 26905592 TI - Regulation of the MET oncogene: molecular mechanisms. AB - The MET oncogene is a predictive biomarker and an attractive therapeutic target for various cancers. Its expression is regulated at multiple layers via various mechanisms. It is subject to epigenetic modifications, i.e. DNA methylation and histone acetylation. Hypomethylation and acetylation of the MET gene have been associated with its high expression in some cancers. Multiple transcription factors including Sp1 and Ets-1 govern its transcription. After its transcription, METmRNA is spliced into multiple species in the nucleus before being transported to the cytoplasm where its translation is modulated by at least 30 microRNAs and translation initiation factors, e.g. eIF4E and eIF4B. METmRNA produces a single chain pro-Met protein of 170 kDa which is cleaved into alpha and beta chains. These two chains are bound together through disulfide bonds to form a heterodimer which undergoes either N-linked or O-linked glycosylation in the Golgi apparatus before it is properly localized in the membrane. Upon interactions with its ligand, i.e. hepatocyte growth factor (HGF), the activity of Met kinase is boosted through various phosphorylation mechanisms and the Met signal is relayed to downstream pathways. The phosphorylated Met is then internalized for subsequent degradation or recycle via proteasome, lysosome or endosome pathways. Moreover, the Met expression is subject to autoregulation and activation by other EGFRs and G-protein coupled receptors. Since deregulation of the MET gene leads to cancer and other pathological conditions, a better understanding of the MET regulation is critical for Met-targeted therapeutics. PMID- 26905593 TI - Erratum to: The interrelations between spiritual well-being, pain interference and depressive symptoms in patients with multiple sclerosis. PMID- 26905594 TI - Endovascular repair of blunt axillo-subclavian arterial injuries as the first line treatment. AB - AIM: To report and analyse our results regarding the endovascular management of blunt axillo-subclavian arterial injuries as the first line treatment. METHODS: During an eight-year period, seven patients (mean age 56.4+/-14.1 years, all males) with blunt traumatic axillo-subclavian arterial injuries were presented to the emergency department. All patients suffered also from concomitant other injuries and had a supraclavicular haematoma along with diminished or absent upper limb peripheral pulses, while computed tomography angiography set the diagnosis. RESULTS: The endovascular procedure was technically successful in all patients. No procedure-related complication was encountered during the in hospital stay, while none of the patients died. The median hospital stay was 22 days (range 12-46). During a follow-up period spanning an average of 27 months (range 6-44 months) there was one stent-graft thrombosis at 12 months in an otherwise asymptomatic patient that required no further intervention. CONCLUSION: Endovascular technique seems to constitute a reliable approach for treating blunt axillo-subclavian arterial injuries in the emergent setting. Despite uncertainties in patient selection and optimal management algorithms, it seems that endovascular approach could be the first line treatment for such injuries. Accumulation of data on larger number of patients with longer follow-up is warranted to further define the value of this therapeutic modality in the trauma setting. PMID- 26905591 TI - Identification of the CIMP-like subtype and aberrant methylation of members of the chromosomal segregation and spindle assembly pathways in esophageal adenocarcinoma. AB - The incidence of esophageal adenocarcinoma (EAC) has risen significantly over recent decades. Although survival has improved, cure rates remain poor, with <20% of patients surviving 5 years. This is the first study to explore methylome, transcriptome and ENCODE data to characterize the role of methylation in EAC. We investigate the genome-wide methylation profile of 250 samples including 125 EAC, 19 Barrett's esophagus (BE), 85 squamous esophagus and 21 normal stomach. Transcriptome data of 70 samples (48 EAC, 4 BE and 18 squamous esophagus) were used to identify changes in methylation associated with gene expression. BE and EAC showed similar methylation profiles, which differed from squamous tissue. Hypermethylated sites in EAC and BE were mainly located in CpG-rich promoters. A total of 18575 CpG sites associated with 5538 genes were differentially methylated, 63% of these genes showed significant correlation between methylation and mRNA expression levels. Pathways involved in tumorigenesis including cell adhesion, TGF and WNT signaling showed enrichment for genes aberrantly methylated. Genes involved in chromosomal segregation and spindle formation were aberrantly methylated. Given the recent evidence that chromothripsis may be a driver mechanism in EAC, the role of epigenetic perturbation of these pathways should be further investigated. The methylation profiles revealed two EAC subtypes, one associated with widespread CpG island hypermethylation overlapping H3K27me3 marks and binding sites of the Polycomb proteins. These subtypes were supported by an independent set of 89 esophageal cancer samples. The most hypermethylated tumors showed worse patient survival. PMID- 26905596 TI - Polarization Drift Channel Model for Coherent Fibre-Optic Systems. AB - A theoretical framework is introduced to model the dynamical changes of the state of polarization during transmission in coherent fibre-optic systems. The model generalizes the one-dimensional phase noise random walk to higher dimensions, accounting for random polarization drifts, emulating a random walk on the Poincare sphere, which has been successfully verified using experimental data. The model is described in the Jones, Stokes and real four-dimensional formalisms, and the mapping between them is derived. Such a model will be increasingly important in simulating and optimizing future systems, where polarization multiplexed transmission and sophisticated digital signal processing will be natural parts. The proposed polarization drift model is the first of its kind as prior work either models polarization drift as a deterministic process or focuses on polarization-mode dispersion in systems where the state of polarization does not affect the receiver performance. We expect the model to be useful in a wide range of photonics applications where stochastic polarization fluctuation is an issue. PMID- 26905595 TI - Globus Pallidus Externus Neurons Expressing parvalbumin Interconnect the Subthalamic Nucleus and Striatal Interneurons. AB - The globus pallidus externus (GP) is a nucleus of the basal ganglia (BG), containing GABAergic projection neurons that arborize widely throughout the BG, thalamus and cortex. Ongoing work seeks to map axonal projection patterns from GP cell types, as defined by their electrophysiological and molecular properties. Here we use transgenic mice and recombinant viruses to characterize parvalbumin expressing (PV+) GP neurons within the BG circuit. We confirm that PV+ neurons 1) make up ~40% of the GP neurons 2) exhibit fast-firing spontaneous activity and 3) provide the major axonal arborization to the STN and substantia nigra reticulata/compacta (SNr/c). PV+ neurons also innervate the striatum. Retrograde labeling identifies ~17% of pallidostriatal neurons as PV+, at least a subset of which also innervate the STN and SNr. Optogenetic experiments in acute brain slices demonstrate that the PV+ pallidostriatal axons make potent inhibitory synapses on low threshold spiking (LTS) and fast-spiking interneurons (FS) in the striatum, but rarely on spiny projection neurons (SPNs). Thus PV+ GP neurons are synaptically positioned to directly coordinate activity between BG input nuclei, the striatum and STN, and thalamic-output from the SNr. PMID- 26905597 TI - Familial searching on DNA mixtures with dropout. AB - Familial searching, the act of searching a database for a relative of an unknown individual whose DNA profile has been obtained, is usually restricted to cases where the DNA profile of that person has been unambiguously determined. Therefore, it is normally applied only with a good quality single source profile as starting point. In this article we investigate the performance of the method if applied to mixtures with and without allelic dropout, when likelihood ratios are computed with a semi-continuous (binary) model. We show that mixtures with dropout do not necessarily perform worse than mixtures without, especially if some separation between the donors is possible due to their different dropout probabilities. The familial searching true and false positive rates of mixed profiles on 15 loci are in some cases better than those of single source profiles on 10 loci. Thus, the information loss due to the fact that the person of interest's DNA has been mixed with that of other, and is affected by dropout, can be less than the loss of information corresponding to having 5 fewer loci available for a single source trace. Profiles typed on 10 autosomal loci are often involved in familial searching casework since many databases, including the Dutch one, in part consist of such profiles. Therefore, from this point of view, there seems to be no objection to extend familial searching to mixed or degraded profiles. PMID- 26905599 TI - Molecular targets of quercetin with anti-inflammatory properties in atopic dermatitis. AB - Atopic dermatitis (AD) is an inflammatory skin disease. Over the past few decades, AD has become more prevalent worldwide. Quercetin, a naturally occurring polyphenol, shows antioxidant, anti-inflammatory, and antiallergic activities. Several recent clinical and preclinical findings suggest quercetin as a promising natural treatment for inflammatory skin diseases. Significant progress in elucidating the molecular mechanisms underlying the anti-AD properties of quercetin has been achieved in the recent years. Here, we discuss the use of quercetin as treatment for AD, with a particular focus on the molecular basis of its effect. We also briefly discuss the approaches to improve the bioavailability of quercetin. PMID- 26905600 TI - Targeting fatty acid metabolism in heart failure: is it a suitable therapeutic approach? AB - The energy substrate preference of the human heart is well regulated and is modified upon aging, in that the fetal heart uses glucose, whereas the adult heart utilizes fatty acids. Various human and animal studies suggest a shift in myocardial substrate utilization and decreased rate of myocardial fatty acid uptake and oxidation in heart failure. Given that fatty acids provide greater capacity for energy production compared with glucose, reverting the heart back to using fatty acids might be a therapeutic option for treating heart failure. Targeting the enzymes and/or genes responsible for, or controlling, fatty acid metabolism in the heart, such as peroxisome proliferator-activated receptors (PPARs), mitochondrial fatty acid metabolizing proteins, AMP-activated protein kinase (AMPK), and glucose transporters (GLUTs), could provide novel therapeutic insights for treating heart failure. PMID- 26905601 TI - Topological Crystalline Insulator in a New Bi Semiconducting Phase. AB - Topological crystalline insulators are a type of topological insulators whose topological surface states are protected by a crystal symmetry, thus the surface gap can be tuned by applying strain or an electric field. In this paper we predict by means of ab initio calculations a new phase of Bi which is a topological crystalline insulator characterized by a mirror Chern number nM = -2, but not a strong topological insulator. This system presents an exceptional property: at the (001) surface its Dirac cones are pinned at the surface high symmetry points. As a consequence they are also protected by time-reversal symmetry and can survive against weak disorder even if in-plane mirror symmetry is broken at the surface. Taking advantage of this dual protection, we present a strategy to tune the band-gap based on a topological phase transition unique to this system. Since the spin-texture of these topological surface states reduces the back-scattering in carrier transport, this effective band-engineering is expected to be suitable for electronic and optoelectronic devices with reduced dissipation. PMID- 26905602 TI - Low Serum Vitamin D: A Surrogate Marker for Advanced Colon Adenoma? AB - AIMS: To examine the association between low 25-OH Vitamin D levels and prevalence of advanced adenomas (AAs) in screening/surveillance colonoscopy patients. RATIONALE: Low serum 25-OH Vitamin D has been associated with an increased risk for colon cancer. In the Adenoma-Carcinoma pathway, a subset of colon polyps (AA) have been regarded as high-risk precursor lesions. We used a retrospective case-control design to examine the association between Vitamin D deficiency and the prevalence of AA in a high-risk population. MATERIALS AND METHODS: We examined a total of 354 patients who presented for initial screening or surveillance colonoscopy at our Colon Cancer Prevention Program. Our main exposure variable was serum Vitamin D levels and the outcome was AAs defined as those adenomas that were large (>=1 cm) or had advanced pathology (>25% villous components or high-grade dysplasia). Known risk factors were also collected from the patients' charts including gender, age, smoking, and family history. Bivariate and multivariate analyses were performed to examine the relationship between serum 25-OH Vitamin D levels and AAs. A total of 354 patients [(males, 188; females, 166); average age, 61 y] charts were reviewed. Vitamin D levels ranged between 4 and 70 ng/mL, with a mean of 25 ng/mL (clinical laboratory normal>30 ng/mL). There was no significant association between serum levels and time of the year of blood draw. Risk for tubular adenoma and AA increased as Vitamin D levels decreased to <30 ng/mL (P=0.002). In total, 80% of AAs were detected in patients whose levels were below this value (odds ratio, 3.36; 95% confidence interval, 1.40-8.03; P=0.007). Bivariate analysis also showed a positive association between smokers with AA as well as those with a family history of colon cancer (P=0.011) and low Vitamin D levels (P=0.001). A multivariate analysis using quintiles of Vitamin D levels demonstrated an increased risk of AAs for patients with levels in the second quintile (33 ng/mL) (odds ratio, 4.3; P=0.01) MAIN CONCLUSIONS:: Most patients presenting in our Colon Cancer Prevention Program have low levels of serum 25-OH Vitamin D. Analysis of the results of both screening and surveillance colonoscopies demonstrated an inverse relation between serum 25-OH Vitamin D level and AAs. PMID- 26905603 TI - Folic Acid Supplementation May Reduce Colorectal Cancer Risk in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis. AB - GOALS: To evaluate the role of folic acid supplementation in colorectal cancer (CRC) chemoprevention in patients with inflammatory bowel disease (IBD). BACKGROUND: CRC is a serious complication of IBD. Folic acid supplementation has been shown to be chemopreventative in sporadic CRC. Patients with IBD are at risk of folate deficiency though intestinal malabsorption and also competitive inhibition by concurrent sulfasalazine use. To date, there have been several studies reporting on folic acid supplementation in patients with IBD and CRC. STUDY: We searched electronic databases for studies reporting folic acid use and CRC incidence in patients with IBD. We produced a pooled hazard ratio with 95% confidence intervals using a random-effects model. Preplanned subgroup analyses were performed to explore for any potential sources of heterogeneity. RESULTS: Ten studies reporting on 4517 patients were included. We found an overall protective effect for folic acid supplementation on the development of CRC, pooled hazard ratio=0.58 (95% confidence interval, 0.37-0.80). There was low to moderate heterogeneity among studies, I=29.7%. Subgroup analyses suggested that folic acid use was protective in hospital-based studies, studies from North America and those that were performed before folate fortification of foods in 1998. CONCLUSIONS: CRC remains an important complication of IBD. Chemoprevention is an attractive strategy and folic acid as a cheap, safe, and well-tolerated supplement may have a role. Focused prospective studies are required to precisely define any potential effect. PMID- 26905605 TI - Extending Colorectal Cancer Screening to Persons Aged 40 to 49 Years With Immunochemical Fecal Occult Blood Test: A Prospective Cohort Study of 513,283 Individuals. AB - GOALS: To assess the association between the initial immunochemical fecal occult blood tests (FIT) and subsequent colorectal cancer, and to explore the ability of FIT to identify individuals age 40 to 49 years with a higher cancer risk. BACKGROUND: The number of cancer cases in this age group is increasing globally and the cancers found in younger age tend to be more advanced than in older age. METHODS: A total of 513,283 individuals had FIT as part of their self-paying medical screening program between 1994 and 2008. The initial FIT test was used. When matched with the Taiwan cancer registry, the cohort identified 2138 colorectal cancer cases. The number needed to screen (NNS) to identify 1 cancer was calculated from the reciprocal of cancer incidence cases during the study period. RESULTS: One in 7 colorectal cancers above age 40 years occurred in the age group of 40 to 49 years. Individuals 40 to 49 years old with positive FIT (>=100 ng/mL) had a 3 times larger cancer risk than those 50 to 59 years old and without FIT, or double the cancer risk as those 50 to 69 years old and without FIT, with NNS at 42, 135, and 95, respectively. A similar relationship existed for the cancer incidence rate. The HR for ages 40 to 44 years or 45 to 49 years with a positive FIT was 2.3 or 5.7 times larger than the HR for ages 50 to 54 years. There was a dose-response relationship between increasing FIT values and the cancer risk for each age group, including ages 40 to 49 years. CONCLUSIONS: Offering FIT to individuals 40 to 49 years of age could identify higher-risk individuals earlier for follow-up colonoscopy, and could, in turn, reduce cancer mortality. PMID- 26905604 TI - Clinical Outcomes, Efficacy, and Adverse Events in Patients Undergoing Esophageal Stent Placement for Benign Indications: A Large Multicenter Study. AB - INTRODUCTION: Esophageal stents are commonly used to treat benign esophageal conditions including refractory benign esophageal strictures, anastomotic strictures, fistulae, perforations and anastomotic leaks. Data on outcomes in these settings remain limited. METHODS: We performed a retrospective multicenter study of patients who underwent fully or partially covered self-expandable stent placement for benign esophageal diseases. Esophageal stent placements were performed for the following indications: (1) benign refractory esophageal strictures, (2) surgical anastomotic strictures, (3) esophageal perforations, (4) esophageal fistulae, and (5) surgical anastomotic leaks. RESULTS: A total of 70 patients underwent esophageal stent placement for benign esophageal conditions. A total of 114 separate procedures were performed. The most common indication for esophageal stent placement was refractory benign esophageal stricture (48.2%). Global treatment success rate was 55.7%. Treatment success rate was 33.3% in refractory benign strictures, 23.1% in anastomotic strictures, 100% in perforations, 71.4% in fistulae, and 80% in anastomotic leaks. Stent migration was noted in 28 of 70 patients (40%), most commonly seen in refractory benign strictures. CONCLUSIONS: This is one of the largest studies to date of esophageal stents to treat benign esophageal diseases. Success rates are lowest in benign esophageal strictures. These patients have few other options beyond chronic dilations, feeding tubes, and surgery, and fully covered self-expandable metallic stent give patients a chance to have their problem fixed endoscopically and still eat by mouth. Perforations, fistulas, and leaks respond very well to esophageal stenting, and stenting should be considered as a first-line therapy in these settings. PMID- 26905606 TI - Histamine H2-Receptor Antagonist Use Is Associated With Lower Prevalence of Nonalcoholic Fatty Liver Disease: A Population-based Study From the National Health and Nutrition Examination Survey, 2001-2006. AB - BACKGROUND & AIM: Recent basic mechanistic studies found that proton-pump inhibitors (PPIs) or histamine antagonists inhibited multiple pathways involved in nonalcoholic fatty liver disease (NAFLD) development. The aim of this study was to investigate an association between PPIs or H1/H2-receptor antagonist (H1RA/H2RA) use and NAFLD prevalence in the general US population. METHODS: We conducted a cross-sectional analysis of data from the National Health and Nutrition Examination Survey, 2001-2006. We included 10,398 adults aged 20 to 74 years who had alanine aminotransferase data; of those, 2058 were identified as having NAFLD and 8340 as controls. PPI or H1RA/H2RA use was defined as use of prescription medications in the preceding month. The length of use was categorized as <=60 days and >60 days. NAFLD was defined as elevated serum aminotransferases without any indication of other causes of chronic liver disease. RESULTS: In the multivariate unconditional logistic regression analysis, H2RA use was inversely associated with prevalent NAFLD [odds ratio (OR)=0.43, 95% confidence interval (CI), 0.18-0.99], a finding that was primarily limited to men (OR=0.18, 95% CI, 0.04-0.79) and those with insulin resistance (OR=0.22, 95% CI, 0.05-0.95). However, no significant associations were found between PPI or H1RA use and prevalent NAFLD. CONCLUSIONS: These findings, from the first human study to investigate an association of PPI or H1RA/H2RA use with NAFLD, suggest that H2RA use may be associated with a lower prevalence of NAFLD, primarily among men with insulin resistance. PMID- 26905607 TI - Successful Treatment of HCV-associated B-Cell Non-Hodgkin Lymphomas With Direct acting Antiviral Agents. PMID- 26905608 TI - One-step synthesis of hollow porous gold nanoparticles with tunable particle size for the reduction of 4-nitrophenol. AB - Hollow porous gold nanoparticles (HPGNPs) were synthesized via a one-step solution phase method at ambient temperature. The particle size, ranging from 80nm to 350nm, was easily controlled by changing the concentration of HAuCl4. The morphology and the structure of the as-prepared HPGNPs were investigated by SEM, TEM, HRTEM and XPS. Langmuir isotherm analysis yielded values of 8973m(2)/g for the outer surface area and 58724m(2)/g for the inner surface area for the 80nm HPGNPs. Due to a special hollow porous nanostructure, the HPGNPs exhibited superior catalytic activity and stability for the reduction of 4-nitrophenol (4 NP). No significant inactivation of the 80nm HPGNPs was observed, even after recycling for six cycles or storing for more than 1 month. Due to these excellent properties, it is expected that HPGNPs can be used in such applications as water pollutant removal and environmental remediation. PMID- 26905609 TI - The role of counter ions in nano-hematite synthesis: Implications for surface area and selenium adsorption capacity. AB - Nano metal oxides are of interest for aqueous selenium (Se) remediation, and as such, nano-hematite (nalpha-Fe2O3) was examined for use as a Se adsorbent. The effect of surface area on adsorption was also studied. nalpha-Fe2O3 particles were synthesized from Fe(NO3)3 and FeCl3 via forced hydrolysis. The resulting particles have similar sizes, morphologies, aggregate size, pore size, and PZC. The nalpha-Fe2O3 from FeCl3 (nalpha-Fe2O3-C) differs from the nalpha-Fe2O3 from Fe(NO3)3 (nalpha-Fe2O3-N) with a ~25+/-2m(2)/g greater surface area. Selenite Se(IV) adsorption capacity on nalpha-Fe2O3 has a qmax ~17mg/g for the freeze dried and re-suspended nalpha-Fe2O3. The Deltaqmax for nalpha-Fe2O3 from Fe(NO3)3 and FeCl3 that remained in suspension was 4.6mg/g. For selenate Se(VI), the freeze-dried and re-suspended particles realize a Deltaqmax= 1.5mg/g for nalpha Fe2O3 from Fe(NO3)3 and FeCl3. The nalpha-Fe2O3 from Fe(NO3)3 and FeCl3 that remained in suspension demonstrated Se(VI) Deltaqmax=5.4mg/g. In situ ATR-FTIR isotherm measurements completed for Se(VI) at a pH 6 suggest that Se(VI) forms primarily outer-sphere complexes with nalpha-Fe2O3 synthesized from both salts. PMID- 26905610 TI - Abiotic reduction of trifluralin and pendimethalin by sulfides in black-carbon amended coastal sediments. AB - Dinitroaniline herbicides such as trifluralin and pendimethalin are persistent bioaccumulative toxins to aquatic organisms. Thus, in-situ remediation of contaminated sediments is desired. This study investigated whether black carbons (BCs), including apple wood charcoal (BC1), rice straw biochar (BC2), and activated carbon (BC3), could facilitate abiotic reduction of trifluralin and pendimethalin by sulfides of environmentally-relevant concentrations in anoxic coastal sediments. The reduction rates of trifluralin and pendimethalin increased substantially with increasing BC dosages in the sediments. This enhancing effect was dependent on BC type with the greatest for BC3 followed by BC1 and BC2, which well correlated with their specific surface area. The pseudo-first order reduction rate constants (kobs) for BC3-amended sediment (2%) were 13- and 14 times the rate constants in the BC-free sediment. The reduction rates increased with increasing temperature from 8 to 25 degrees C in the BC-amended sediment, following the Arrhenius relationship. Finally, through molecular modeling by density functional theory and reaction species identification from mass spectra, molecular pathways of trifluralin and pendimethalin reduction were elucidated. In contrary to the separate sequential reduction of each nitro group to amine group, both nitro groups, first reduced to nitroso, then eventually to amine groups. PMID- 26905611 TI - Enhancing the reactivity of bimetallic Bi/Fe(0) by citric acid for remediation of polluted water. AB - In this study, the environmentally benign citric acid (CA) was utilized to improve the aerobic degradation of 4-chlorophenol (4-CP) over bismuth modified nanoscale zero-valent iron (Bi/Fe(0)). The characterization results revealed the existence of bismuth covering on the Fe(0) surface under zero-valent state. And, the Bi/Fe(0)-CA+O2 system performed excellent reactivity in degradation of 4-CP due to the generation of reactive oxygen species (ROS), which was confirmed by electron spin resonance (ESR) spectroscopy. After 30min of reaction, 80% of 4-CP was removed using Bi/Fe(0)-CA+O2 accompanying with high dechlorination rate. The oxidative degradation intermediates were analyzed by HPLC and LC-MS. We found that CA could promote the bismuth-iron system to produce much reactive oxygen species ROS under both aerobic and anaerobic conditions due to its ligand function, which could react with Fe(3+) to form a ligand complex (Fe(III)Cit), accompanying with a considerable production of Fe(2+) and H2O2. This study provides a new strategy for generating ROS on nZVI and suggests its application for the mineralization of many recalcitrant pollutants. PMID- 26905612 TI - Ecological risk assessment associated to the removal of endocrine-disrupting parabens and benzophenone-4 in wastewater treatment. AB - The occurrence of four widely used and endocrine disrupting parabens (PBs) (methylparaben, propylparaben, butylparaben and benzylparaben) and a polar UV filter (benzophenone-4) were determined in influent and effluent wastewater from the 19 major wastewater treatment plants (WWTPs) of Catalonia, Spain. For their analysis an on-line solid-phase extraction-liquid chromatography-tandem mass spectrometry (SPE-HPLC-MS/MS) method was developed and validated. Laboratory analysis revealed high levels for both PBs and BP4, with maximum concentrations of 5700ngL(-1) and 1806ngL(-1), respectively, in influent samples, and 137ngL(-1) and 1080ngL(-1), respectively in effluent wastewaters. Removal rates (RE%) for the target compounds in each WWTPs were calculated. RE% for parabens were almost 100%, whereas for BP4 values where in the range 5-91%. The half-life time (t1/2), hydraulic retention time (HRT), and annual mass load (ML) for each facility was estimated. Results indicated that there was no clear influence of HRT on the RE% of BP4. MLs for BP4 were in the range 0.9-110.1kgy(-1), with the highest values in the most populated areas. Finally, a risk assessment, estimated in terms of hazard quotients (HQs), was carried out for aquatic biota. HQs for the target compounds in effluent wastewaters indicated a negligible effect, whereas for some influent wastewaters' HQs pointed out that some species are at risk. PMID- 26905615 TI - Italian Bipolar II vs I patients have better individual functioning, in spite of overall similar illness severity. AB - : Introduction Bipolar disorders (BDs) comprise different variants of chronic, comorbid, and disabling conditions, with relevant suicide and suicide attempt rates. The hypothesis that BD types I (BDI) and II (BDII) represent more and less severe forms of illness, respectively, has been increasingly questioned over recent years, justifying additional investigation to better characterize related sociodemographic and clinical profiles. METHODS: A sample of 217 outpatients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR)-described BD (141 BDI, 76 BDII), without a current syndromal mood episode, was recruited, and sociodemographic and clinical characteristics of BDI and II patients were compared. RESULTS: BDII patients had significantly more favorable sociodemographics, in relation to occupational stability, cohabitation, and marital status. However, BDII compared with BDI patients had significantly longer duration of untreated illness, more frequent lifetime anxiety disorders comorbidity, longer most recent episode duration, higher rate of depressive first/most recent episode, and more current antidepressant use. In contrast, BDI compared with BDII patients had significantly more severe illness in terms of earlier age at onset; higher rate of elevated first/most recent episode, lifetime hospitalizations, and involuntary commitments; lower Global Assessment of Functioning score; and more current antipsychotic use. BDI and II patients had similar duration of illness, psychiatric family history, lifetime number of suicide attempts, current subthreshold symptoms, history of stressful life events, and overall psychiatric/medical comorbidity. CONCLUSION: BDII compared with BDI patients had more favorable sociodemographic features, but a mixture of specific unfavorable illness characteristics, confirming that BDII is not just a milder form of BD and requires further investigation in the field. PMID- 26905616 TI - Biocompatible hydrogelators based on bile acid ethyl amides. AB - Four novel bile acid ethyl amides were synthetized using a well-known method. All the four compounds were characterized by IR, SEM, and X-ray crystal analyses. In addition, the cytotoxicity of the compounds was tested. Two of the prepared compounds formed organogels. Lithocholic acid derivative 1 formed hydrogels as 1% and 2% (w/v) in four different aqueous solutions. This is very intriguing regarding possible uses in biomedicine. PMID- 26905617 TI - Ageing, Drama, and Creativity: Translating Research Into Practice. AB - Ageing, Drama, and Creativity was a pilot six-session interprofessional training course delivered collaboratively by Keele University and the New Vic Theatre, Newcastle-under-Lyme, as part of our Arts and Humanities Research Council (AHRC) funded Ages and Stages follow-on project. The course brought together a critical gerontological approach with arts-based educational practices and was designed to develop practice capabilities and age awareness among a diverse group of professionals working in arts organizations, the voluntary sector, local government, health and social services, and housing. This article describes how the course was developed and how participants were selected, details its aims and objectives, provides an overview of the sessions and a flavor of some of the exercises that were used, and considers findings from the structured evaluation alongside written reflections from participants. PMID- 26905618 TI - Increasing wrist fracture rates in children may have major implications for future adult fracture burden. AB - Background and purpose - Childhood fractures are associated with lower peak bone mass (a determinant of osteoporosis in old age) and higher adult fracture risk. By examining time trends in childhood fracture epidemiology, it may be possible to estimate the vector of fragility fracture risk in the future. Patients and methods - By using official inpatient and outpatient data from the county of Skane in Sweden, 1999-2010, we ascertained distal forearm fractures in children aged <= 16 years and estimated overall and age- and sex-specific rates and time trends (over 2.8 million patient years) and compared the results to earlier estimations in the same region from 1950 onwards. Results - During the period 1999-2010, the distal forearm fracture rate was 634 per 10(5) patient years (750 in boys and 512 in girls). This was 50% higher than in the 1950s with a different age-rate distribution (p < 0.001) that was most evident during puberty. Also, within the period 1999-2010, there were increasing fracture rates per 10(5) and year (boys +2.0% (95% CI: 1.5-2.6), girls +2.4% (95% CI: 1.7-3.1)). Interpretation - The distal forearm fracture rate in children is currently 50% higher than in the 1950s, and it still appears to be increasing. If this higher fracture risk follows the children into old age, numbers of fragility fractures may increase sharply-as an upturn in life expectancy has also been predicted. The origin of the increase remains unknown, but it may be associated with a more sedentary lifestyle or with changes in risk behavior. PMID- 26905620 TI - Commentary on 'Content Validation and Evaluation of an Endovascular Teamwork Assessment Tool'. PMID- 26905619 TI - Semipermeable Capsules Wrapping a Multifunctional and Self-regulated Co-culture Microenvironment for Osteogenic Differentiation. AB - A new concept of semipermeable reservoirs containing co-cultures of cells and supporting microparticles is presented, inspired by the multi-phenotypic cellular environment of bone. Based on the deconstruction of the "stem cell niche", the developed capsules are designed to drive a self-regulated osteogenesis. PLLA microparticles functionalized with collagen I, and a co-culture of adipose stem (ASCs) and endothelial (ECs) cells are immobilized in spherical liquified capsules. The capsules are coated with multilayers of poly(L-lysine), alginate, and chitosan nano-assembled through layer-by-layer. Capsules encapsulating ASCs alone or in a co-culture with ECs are cultured in endothelial medium with or without osteogenic differentiation factors. Results show that osteogenesis is enhanced by the co-encapsulation, which occurs even in the absence of differentiation factors. These findings are supported by an increased ALP activity and matrix mineralization, osteopontin detection, and the up regulation of BMP-2, RUNX2 and BSP. The liquified co-capsules also act as a VEGF and BMP-2 cytokines release system. The proposed liquified capsules might be a valuable injectable self-regulated system for bone regeneration employing highly translational cell sources. PMID- 26905621 TI - Peripheral Arterial Disease Incidence and Associated Risk Factors in a Mediterranean Population-based Cohort. The REGICOR Study. AB - OBJECTIVES: The reported incidence of lower extremity peripheral arterial disease (PAD) in Western countries ranges between 530 and 2,380 per 100,000 person years. The aims of this study were to determine the incidence of PAD and identify associated risk factors in a Mediterranean population. METHODS: Cardiovascular risk factors, the Edinburgh questionnaire, and ankle brachial index (ABI) were collected from 5,434 individuals, aged 35-79 years, from a population based cohort study at baseline and after a mean of 5.7 years follow up. PAD was defined as ABI <0.9 or a clinical diagnosis during follow up. Logistic and regression tree analyses were used to identify factors associated with PAD. RESULTS: In total, 118 new cases of confirmed PAD were identified. The cumulative population incidence rate of PAD was 377 cases per 100,000 person years. For symptomatic PAD, this figure was 102 per 100,000 person years. The most important risk factors for PAD were current (OR 2.30; 95% CI 1.27-4.16) or former smoking (OR 2.02; 95% CI 1.19-3.43), diabetes (OR 1.78; 95% CI 1.17-2.72), age (OR 1.04; 95% CI 1.02-1.07), history of cardiovascular disease (OR 2.06; 95% CI 1.22-3.51), triglycerides level (OR 1.56; 95% CI 1.07-2.29), and systolic blood pressure (OR 1.02; 95% CI 1.01-1.03). In the population <=65 years the most relevant risk factor was diabetes, whereas in those >65 years smoking was the leading factor. Long-term uncontrolled diabetes was the strongest risk factor for PAD (OR 10.14; 95% CI 3.57-28.79). CONCLUSION: The incidence of lower extremity PAD is lower in the Mediterranean area than has been reported for other areas. The data suggest that patients with long-term uncontrolled diabetes and former and current smokers older than 65 years should be considered for PAD screening. PMID- 26905622 TI - Five Year Outcomes of Surgical Treatment for Popliteal Artery Entrapment Syndrome. AB - OBJECTIVE/BACKGROUND: The aim of this study was to evaluate long-term outcomes following surgery for popliteal artery entrapment syndrome. METHODS: A retrospective study of all patients that underwent surgery for popliteal artery entrapment syndrome between January 2003 and December 2009 was performed. Patient demographic data, clinical features, imaging modalities, and surgical management were recorded. The primary outcome was 5 year patency. RESULTS: Eighteen patients (25 limbs) underwent surgery. The mean age at the time of surgical procedure was 35 (median 35 years; range 15-49). Presentation was bilateral in seven patients (39%). Diagnosis was made using various imaging modalities, including position stress test, Duplex ultrasonography, computed tomography angiography, magnetic resonance imaging and conventional angiography. In four limbs the popliteal artery was compressed and undamaged (16%), and treatment consisted of musculo tendinous division alone. In 16 limbs the popliteal artery was damaged with lesions limited to the popliteal artery (64%) where treatment consisted of venous interposition. In five limbs lesions extended beyond the popliteal artery (20%) and procedures included one below knee femoro-popliteal bypass, three femoro posterior tibial bypasses, and one popliteo-posterior tibial bypass. Musculo tendinous division was associated with vascular reconstruction in 19 limbs (90%). Mean follow up was 82 months (median 81 months, range 60-120). Five year patency was 84%. CONCLUSION: Long-term outcomes of surgical procedures performed for popliteal artery entrapment syndrome can be considered satisfactory. PMID- 26905623 TI - Commentary on 'Positron Emission Tomography and Magnetic Resonance Imaging of Cellular Inflammation in Patients with Abdominal Aortic Aneurysms'. PMID- 26905624 TI - Axillo-bifemoral Vascular Graft Infection Treated by Excision and Contralateral Reconstruction to the Popliteal Artery Through the Obturator Foramen. PMID- 26905625 TI - The Receptor for Advanced Glycation End Products (Rage) and Its Ligands in Plasma and Infrainguinal Bypass Vein. AB - OBJECTIVE: The aim was to investigate whether RAGE and its ligands are associated with infrainguinal bypass outcome in patients with and without diabetes. METHODS: This was a prospective observational cohort. Patients (n = 68) with (n = 38) and without (n = 30) diabetes undergoing infrainguinal vein bypass for peripheral arterial disease were followed for 3 years. Endosecretory RAGE (esRAGE), S100A12, advanced glycation end products, and carboxymethyl-lysine (CML) were determined in plasma using ELISA. The influence of plasma levels on the main outcome (amputation free survival) was evaluated using Cox proportional hazard analysis. Plasma esRAGE, CML, and S100A12 in healthy controls (n = 30) without cardiovascular disease matched for sex and age were compared with patients, using the Mann-Whitney U test. Veins from bypass surgery procedures were stained and S100A12, RAGE, AGE, and CML were determined using immunohistochemistry. RESULTS: Forty-six patients survived with an intact leg during follow up. Seventeen died (median survival time 702 days, IQR 188-899 day), and six had amputations. High plasma S100A12 was associated with reduced amputation free survival (hazard ratio [HR] 2.99; 95% CI 1.24-7.24) when comparing levels above the 75th percentile with levels below. The increased risk was unchanged adjusting for age, sex, and diabetes. Diabetic patients had higher plasma S100A12 (11.75 ng/mL; 95% CI 8.12 15.38 ng/mL) than non-diabetic patients (5.0141 ng/mL; 95% CI 3.62-6.41 ng/mL), whereas plasma CML, esRAGE, and AGE were similar. Plasma CML and S100A12 were higher in patients than in controls (1.25 MUg/mL, 95% CI 1.18-1.32 MUg/mL vs. 0.8925 MUg/mL, 95% CI 0.82-0.96 MUg/mL; and 8.7 MUg/mL, 95% CI 6.52-10.95 MUg/mL vs. 3.47 MUg/mL, 95% CI 2.95-3.99 MUg/mL, respectively). The proportion of vein tissue stained for AGE (21%), RAGE (5%), CML (9%) and S100A12 (3%), were similar in patients with and without diabetes. CONCLUSIONS: Plasma S100A12 and CML are elevated in peripheral arterial disease and markers of RAGE and its ligands are found in vein used for bypass. This indicates a role for S100A12, CML, and RAGE in peripheral arterial disease complications by activation of the RAGE system. PMID- 26905626 TI - Registries in Clinical Epidemiology: the European Surveillance System on Contact Allergies (ESSCA). AB - BACKGROUND: Disease registries rely on consistent electronic data capturing (EDC) pertinent to their objectives; either by using existing electronic data as far as available, or by implementing specific software solutions. OBJECTIVES: To describe the current practice of an international disease registry (European Surveillance System on Contact Allergies, ESSCA, www.essca-dc.org) against different state of the art approaches for EDC. METHODS: Since 2002, ESSCA is collecting data, currently from 53 departments in 12 countries. Departmental EDC software ranges from spreadsheets to comprehensive "patch test software" based on a relational database. In the Erlangen data centre, such diverse data is imported, converted to a common format, quality checked and pooled for scientific analyses. RESULTS: Feed-back to participating departments for quality control is provided by standardised reports. Varying author teams publish scientific analyses addressing the objective of contact allergy surveillance. CONCLUSIONS: Although ESSCA represents a historically grown, heterogeneous network and not one unified approach to EDC, some of its features have contributed to its viability in the last 12 years and may be useful to consider for similar investigator initiated networks. PMID- 26905627 TI - Correlation detection strategies in microbial data sets vary widely in sensitivity and precision. AB - Disruption of healthy microbial communities has been linked to numerous diseases, yet microbial interactions are little understood. This is due in part to the large number of bacteria, and the much larger number of interactions (easily in the millions), making experimental investigation very difficult at best and necessitating the nascent field of computational exploration through microbial correlation networks. We benchmark the performance of eight correlation techniques on simulated and real data in response to challenges specific to microbiome studies: fractional sampling of ribosomal RNA sequences, uneven sampling depths, rare microbes and a high proportion of zero counts. Also tested is the ability to distinguish signals from noise, and detect a range of ecological and time-series relationships. Finally, we provide specific recommendations for correlation technique usage. Although some methods perform better than others, there is still considerable need for improvement in current techniques. PMID- 26905628 TI - Ecological succession leads to chemosynthesis in mats colonizing wood in sea water. AB - Chemosynthetic mats involved in cycling sulfur compounds are often found in hydrothermal vents, cold seeps and whale falls. However, there are only few records of wood fall mats, even though the presence of hydrogen sulfide at the wood surface should create a perfect niche for sulfide-oxidizing bacteria. Here we report the growth of microbial mats on wood incubated under conditions that simulate the Mediterranean deep-sea temperature and darkness. We used amplicon and metagenomic sequencing combined with fluorescence in situ hybridization to test whether a microbial succession occurs during mat formation and whether the wood fall mats present chemosynthetic features. We show that the wood surface was first colonized by sulfide-oxidizing bacteria belonging to the Arcobacter genus after only 30 days of immersion. Subsequently, the number of sulfate reducers increased and the dominant Arcobacter phylotype changed. The ecological succession was reflected by a change in the metabolic potential of the community from chemolithoheterotrophs to potential chemolithoautotrophs. Our work provides clear evidence for the chemosynthetic nature of wood fall ecosystems and demonstrates the utility to develop experimental incubation in the laboratory to study deep-sea chemosynthetic mats. PMID- 26905629 TI - Genomic and in situ investigations of the novel uncultured Chloroflexi associated with 0092 morphotype filamentous bulking in activated sludge. AB - Overgrowth of filamentous bacteria in activated sludge wastewater treatment plants (WWTPs) leads to impaired sludge settleability, a condition known as bulking, which is a common operational problem worldwide. Filaments with the Eikelboom 0092 morphotype are commonly associated with such bulking episodes. Members of the uncultured B45 phylotype, which is embraced within the phylum Chloroflexi, were recently shown to exhibit this morphology. Although these organisms are among the most abundant populations recorded in activated sludge processes, nothing is known about their metabolic characteristics. In this study, a genome sequence, representing the B45 phylotype, was retrieved from a metagenome generated from an activated sludge WWTP. The genome consisted of two chromosomes and one plasmid, which were 4.0, 1.0 and 0.04 Mbps in size, respectively. A metabolic model was constructed for this organism, based on annotation of its genome, showing its ability to generate energy by respiration, utilizing oxygen, nitrite or nitrous oxide as electron acceptors, or by fermentation of sugars. The ability of B45 members to ferment sugars under anaerobic conditions was validated in situ with microautoradiography-fluorescence in situ hybridization. The provisional name of 'Candidatus Promineofilum breve' is proposed for this species. This study represents the first detailed information on an uncultured genus of filamentous organisms from activated sludge. PMID- 26905631 TI - Neuraminidase inhibitors for the treatment of influenza infection in people with cystic fibrosis. AB - BACKGROUND: Cystic fibrosis is the most common, life-threatening, recessively inherited disease of Caucasian populations. It is a multisystem disorder caused by a mutation in the gene encoding the cystic fibrosis transmembrane conductance regulator protein which is important in producing sweat, digestive juices and mucus.The impaired or absent function of this protein results in the production of viscous mucus within the lungs and an environment that is susceptible to chronic airway obstruction and pulmonary colonization by a range of pathogenic bacteria. Morbidity and mortality of cystic fibrosis is related to chronic pulmonary sepsis and its complications by these bacteria.Influenza can worsen the course of the disease in cystic fibrosis by increasing the risk of pneumonia and secondary respiratory complications. Antiviral agents form an important part of influenza management and include the neuraminidase inhibitors zanamivir and oseltamivir. These inhibitors can limit the infection and prevent the spread of the virus. OBJECTIVES: To assess the effects of neuraminidase inhibitors for the treatment of influenza infection in people with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Most recent search: 02 November 2015. SELECTION CRITERIA: Randomised controlled trials and quasi-randomised controlled trials comparing neuraminidase inhibitors with placebo or other antiviral drugs. DATA COLLECTION AND ANALYSIS: Two review authors had planned to independently screen studies, extract data and assess risk of bias using standard Cochrane methodologies. No studies were identified for inclusion. MAIN RESULTS: No relevant studies were retrieved after a comprehensive search of the literature. AUTHORS' CONCLUSIONS: We were unable to identify any randomised controlled studies or quasi-randomised controlled studies on the efficacy of neuraminidase inhibitors for the treatment of influenza infection in people with cystic fibrosis. The absence of high level evidence for the effectiveness of these interventions emphasises the need for well-designed, adequately powered, randomised controlled clinical studies. PMID- 26905630 TI - Iron availability shapes the evolution of bacteriocin resistance in Pseudomonas aeruginosa. AB - The evolution of bacterial resistance to conventional antimicrobials is a widely documented phenomenon with gravely important consequences for public health. However, bacteria also produce a vast repertoire of natural antimicrobials, presumably in order to kill competing species. Bacteriocins are a common class of protein-based antimicrobials that have been shown to have an important role in the ecology and evolution of bacterial communities. Relative to the evolution of antibiotic resistance, little is known about how novel resistance to these toxic compounds evolves. In this study, we present results illustrating that, although resistance is able to evolve, it remains critically dependent on the environmental context. Resistance to bacteriocins, in particular the pyocin S2, evolves readily when iron is present but less so when iron is limiting, because the receptor for this pyocin is also required for iron uptake during iron limitation. This suggests that although resistance to bacteriocins can easily evolve, environmental conditions will determine how and when resistance occurs. PMID- 26905632 TI - Change in the Multidimensional Prognostic Index Score During Hospitalization in Older Patients. AB - We investigated and describe change in the Multidimensional Prognostic Index (MPI) score between admission and discharge in 960 older patients admitted to 20 geriatric units for an acute disease or a relapse of a chronic disease. The MPI was calculated at admission and at discharge. Subjects were divided into three groups of MPI score, low risk (MPI-1 value <=0.33), moderate risk (MPI-2 value 0.34-0.66), and severe risk of mortality (MPI-3 value >=0.67), on the basis of previously established cutoffs. Variation of MPI values over length of hospital stay (LOS) was analyzed with a multivariable longitudinal linear model for repeated measurements. At admission, 23.5% subjects had an MPI-1 score, 33.3% had an MPI-2 score, and 43.0% had an MPI-3 score. Overall, for almost 60% of the patients, MPI score at hospital discharge was different compared with the score at admission, although the difference was not statistically significant (-0.003; p = 0.708). Patients with high and intermediate MPI scores at admission had a decrease of MPI score at discharge (delta-MPI -0.026, p < 0.001, and delta-MPI 0.066, p = 0.569, respectively), whereas patients in the MPI-low group, experienced a significant increase in MPI score (delta-MPI 0.041, p < 0.001). The evolution of MPI score as a function of LOS had a curvilinear shape because it significantly decreased for patients with short hospitalization (1-6 days) and tended to increase for those with longer LOS. The MPI, a well-established prognostic tool, is sensitive to change of patient's health status and might be used to objectively track and monitor the clinical evolution of acutely ill geriatric patients admitted to the hospital. PMID- 26905633 TI - Molecular cloning, characterization and expression analysis of (B-cell lymphoma-2 associated X protein) Bax in the orange-spotted grouper (Epinephelus coioides) after the Vibrio alginolyticus challenge. AB - Bax is a pro-apoptotic member of Bcl-2 like superfamily, playing an important role in regulating the apoptosis. In this study, the full-length Bax (EcBax) was obtained, containing a 5'UTR of 64 bp, an ORF of 579 bp and a 3'UTR of 1021 bp. The EcBax gene encoded a polypeptide of 192 amino acids with an estimated molecular mass of 21.55 KDa and a predicted isoelectric point (pI) of 6.75. The deduced amino acid sequence analysis showed that EcBax comprised the conserved residues and the characteristic domains known to the critical function of Bax. qRT-PCR analysis revealed that EcBax mRNA was broadly expressed in all of the examined tissues, while the highest expression level was observed in blood, followed by the expression in liver, gill, spleen, kidney, heart, muscle and intestine. A sharp increase of EcBax expression was observed in the vibrio challenge group by comparing with those in the control. Subcellular localization analysis revealed that EcBax was predominantly localized in the cytoplasm. EcBax exerted a regulatory role in modulating the mitochondrial membrane potential, promoting the cytochrome c release, and then activating the downstream caspase signaling. Moreover, the overexpression of EcBax can decrease the cell viability and antagonize NF-kB, AP-1, Stat3 promoter activity in Hela cells. These results indicate that EcBax containing the conserved domain of pro-apoptotic member of Bcl-2 family may disrupt the mammalian signaling and play a regulative role in the apoptotic process. PMID- 26905634 TI - T cell immunity in the teleost digestive tract. AB - Fish (along with cyclostomes) constitute the most ancient animal group in which an acquired immune system is present. As in higher vertebrates, both B and T lymphocytes cooperate in implementing an adequate response. Although there is still a debate on whether fish possess a true gut associated lymphoid tissue (GALT), the presence of diffuse B and T lymphocytes throughout all mucosal surfaces has been demonstrated in a wide variety of fish species. The lack of antibodies against T lymphocyte markers has hampered the performance of functional assays in both systemic and mucosal compartments. However, most components associated with T lymphocyte function have been identified in fish through extensive genomic research, suggesting similar functionalities for fish and mammalian T lymphocytes. Thus, the aim of this review is to briefly summarize what is known in teleost concerning the characteristics and functionalities of the different T cell subsets, to then focus on what is known to date regarding their presence and role in the gastrointestinal tract, through either direct functional assays or indirectly by conclusions drawn from transcriptomic analysis. PMID- 26905635 TI - Characterisation of CD4 T cells in healthy and diseased koalas (Phascolarctos cinereus) using cell-type-specific monoclonal antibodies. AB - The koala (Phascolarctos cinereus) is an arboreal herbivorous marsupial that is an Australian icon. Koalas in many parts of Australia are under multiple threats including habitat destruction, dog attacks, vehicular accidents, and infectious diseases such as Chlamydia spp. and the koala retrovirus (KoRV), which may contribute to the incidence of lymphoma and leukaemia in this species. Due to a lack of koala-specific immune reagents and assays there is currently no way to adequately analyse the immune response in healthy, diseased or vaccinated animals. This paper reports the production and characterisation of the first anti koala CD4 monoclonal antibody (mAb). The koala CD4 gene was identified and used to develop recombinant proteins for mAb production. Fluorochrome-conjugated anti CD4 mAb was used to measure the levels of CD4(+) lymphocytes collected from koala spleens (41.1%, range 20-45.1%) lymph nodes (36.3%, range 19-55.9%) and peripheral blood (23.8%, range 17.3-35%) by flow cytometry. Biotin-conjugated anti-CD4 mAb was used for western blot to determine an approximate size of 52 kDa for the koala CD4 molecule and used in immunohistochemistry to identify CD4(+) cells in the paracortical region and germinal centres of spleen and lymph nodes. Using the anti-CD4 mab we showed that CD4 cells from vaccinated, but not control, koalas proliferated following in vitro stimulation with UV-inactivated Chlamydia pecorum and recombinant chlamydial antigens. Since CD4(+) T cells have been shown to play a pivotal role in clearing chlamydial infection in both human and mouse infections, using this novel antibody will help determine the role CD4(+) T cells play in protection against chlamydial infection in koalas and also enhance our knowledge of how KoRV affects the koala immune system. PMID- 26905636 TI - Author Reply. PMID- 26905637 TI - Editorial Comment. PMID- 26905638 TI - Pollinosis to tree of heaven (Ailanthus altissima) and detection of allergenic proteins: a case report. PMID- 26905641 TI - Editorial overview: Tumour immunology: What's beyond today's success in tumor immunology. PMID- 26905639 TI - Local and systemic reactions to subcutaneous allergen immunotherapy: Ten years' experience in a pediatric clinic. AB - BACKGROUND: Local and especially systemic reactions are important problems in subcutaneous immunotherapy (SCIT). Local and systemic reactions develop in 0.7% to 4% and 0.2% of all injections, respectively. OBJECTIVE: To evaluate the frequency of and risk factors for reactions developing in pediatric patients undergoing SCIT. METHODS: Local and systemic reactions developing after 14,308 injections between 2003 and 2013 were retrospectively evaluated in the current study using the Subcutaneous Immunotherapy Systemic Reaction Grading System, as recommended by the World Allergy Organization. The type of allergic disease, allergens producing a sensitivity, allergen immunotherapy content, adjuvant content, and the effects of treatment phase on the frequency of adverse effects were investigated. RESULTS: Of 319 patients, local reactions occurred in 11.9%, wide local reactions occurred in 5%, and systemic reactions occurred in 4.7%. A local reaction was observed in 0.38% of all injections, whereas a systemic reaction was observed in 0.1% of all injections. Local reactions were most frequent in the build-up phase, and systemic reactions were most frequent in the maintenance phase (P = .01). Side reactions were more common in patients undergoing SCIT with multiple allergens (P = .002) and house dust mite (P = .001). No statistically significant difference was found between adjuvant content and adverse effect frequency (P = .32). CONCLUSIONS: The frequencies of local and wide local reactions during SCIT were lower than expected. Although systemic reactions were frequently seen, no fatal reaction was observed in the current study. House dust mite SCIT and multiple allergen use increased the risk of reaction. PMID- 26905640 TI - Association among stress, hypocortisolism, systemic inflammation, and disease severity in chronic urticaria. AB - BACKGROUND: Chronic urticaria (CU) is an immune-mediated disease characterized by wheals for at least 6 weeks. The role of stress and the correlation of stress, hypocortisolism, and inflammatory markers are not well understood. OBJECTIVES: To estimate C-reactive protein (CRP), interleukin (IL)-18, and cortisol levels in patients with CU and to explore their association with disease severity and stress. METHODS: Forty-five patients with CU and 45 age- and sex-matched healthy controls were recruited for this cross-sectional study. Disease severity was assessed by the urticaria activity score (UAS) and stress by Presumptive Stressful Life Events (PSLE) and Daily Hassles and Uplifts Scale-Revised (DHUS-R) scoring. IL-18 and high-sensitivity CRP (hs-CRP) were estimated using enzyme linked immunosorbent assay kits and cortisol levels by chemiluminescence. RESULTS: We observed significant systemic inflammation (increased hs-CRP and IL 18 levels) and stress scores, whereas there was a lowering of basal cortisol levels in patients with CU compared with controls. This finding was more pronounced with increasing disease severity and autoimmune disease, except for stress scores, which did not vary between patients with positive and negative autologous plasma skin test results. We further observed that patients with CU with hypocortisolism had higher levels of hs-CRP and IL-18 and higher PSLE and DHUS-R scores compared with those without hypocortisolism. The hs-CRP level, IL 18 level, PSLE score, DHUS-R score, and duration of the symptoms are significantly positively correlated with UAS, whereas the cortisol level is significantly negatively correlated with UAS. Cortisol has a significant negative correlation with PSLE score, DHUS-R score, and the duration of the disease. CONCLUSION: CU is associated with systemic inflammation and stress, along with a significant lower basal cortisol, especially with severe disease and autoimmune urticaria. Thus, chronic stress may precipitate the vicious cycle in the pathogenesis of CU. PMID- 26905642 TI - X-rays Reveal the Internal Structure of Keratin Bundles in Whole Cells. AB - In recent years, X-ray imaging of biological cells has emerged as a complementary alternative to fluorescence and electron microscopy. Different techniques were established and successfully applied to macromolecular assemblies and structures in cells. However, while the resolution is reaching the nanometer scale, the dose is increasing. It is essential to develop strategies to overcome or reduce radiation damage. Here we approach this intrinsic problem by combing two different X-ray techniques, namely ptychography and nanodiffraction, in one experiment and on the same sample. We acquire low dose ptychography overview images of whole cells at a resolution of 65 nm. We subsequently record high resolution nanodiffraction data from regions of interest. By comparing images from the two modalities, we can exclude strong effects of radiation damage on the specimen. From the diffraction data we retrieve quantitative structural information from intracellular bundles of keratin intermediate filaments such as a filament radius of 5 nm, hexagonal geometric arrangement with an interfilament distance of 14 nm and bundle diameters on the order of 70 nm. Thus, we present an appealing combined approach to answer a broad range of questions in soft-matter physics, biophysics and biology. PMID- 26905644 TI - The mechanoelectrical response of droplet interface bilayer membranes. AB - Mechanotransduction and interfacial properties in unsupported liquid biomimetic membranes are explored using the droplet-interface bilayer technique. The fluidic monolayer-membrane system afforded by this technique allows for dynamic control over the membrane dimensions and curvature, which under periodic deformations generates capacitive currents (akin to a Kelvin probe), and permits a detailed electrostatic characterization of the boundary layers as well as observation of flexoelectric effects. Both high and low displacement frequency regimes are examined, and the results show that the mechanoelectric signals generated by the membranes may be linked to the membrane electrostatic structure. In addition, we show that periodic membrane bending in a high-frequency regime generates tension sufficient to activate reconstituted mechanosensitive channels. PMID- 26905643 TI - Residual Detergent Detection Method for Nondestructive Cytocompatibility Evaluation of Decellularized Whole Lung Scaffolds. AB - The development of reliable tissue engineering methods using decellularized cadaveric or donor lungs could potentially provide a new source of lung tissue. The vast majority of current lung decellularization protocols are detergent based and incompletely removed residual detergents may have a deleterious impact on subsequent scaffold recellularization. Detergent removal and quality control measures that rigorously and reliably confirm removal, ideally utilizing nondestructive methods, are thus critical for generating optimal acellular scaffolds suitable for potential clinical translation. Using a modified and optimized version of a methylene blue-based detergent assay, we developed a straightforward, noninvasive method for easily and reliably detecting two of the most commonly utilized anionic detergents, sodium deoxycholate (SDC) and sodium dodecyl sulfate (SDS), in lung decellularization effluents. In parallel studies, we sought to determine the threshold of detergent concentration that was cytotoxic using four different representative human cell types utilized in the study of lung recellularization: human bronchial epithelial cells, human pulmonary vascular endothelial cells (CBF12), human lung fibroblasts, and human mesenchymal stem cells. Notably, different cells have varying thresholds for either SDC or SDS-based detergent-induced cytotoxicity. These studies demonstrate the importance of reliably removing residual detergents and argue that multiple cell lines should be tested in cytocompatibility-based assessments of acellular scaffolds. The detergent detection assay presented here is a useful nondestructive tool for assessing detergent removal in potential decellularization schemes or for use as a potential endpoint in future clinical schemes, generating acellular lungs using anionic detergent-based decellularization protocols. PMID- 26905645 TI - Reliable and versatile immortal muscle cell models from healthy and myotonic dystrophy type 1 primary human myoblasts. AB - Primary human skeletal muscle cells (hSkMCs) are invaluable tools for deciphering the basic molecular mechanisms of muscle-related biological processes and pathological alterations. Nevertheless, their use is quite restricted due to poor availability, short life span and variable purity of the cells during in vitro culture. Here, we evaluate a recently published method of hSkMCs immortalization, relying on ectopic expression of cyclin D1 (CCND1), cyclin-dependent kinase 4 (CDK4) and telomerase (TERT) in myoblasts from healthy donors (n=3) and myotonic dystrophy type 1 (DM1) patients (n=2). The efficacy to maintain the myogenic and non-transformed phenotype, as well as the main pathogenetic hallmarks of DM1, has been assessed. Combined expression of the three genes i) maintained the CD56(NCAM)-positive myoblast population and differentiation potential; ii) preserved the non-transformed phenotype and iii) maintained the CTG repeat length, amount of nuclear foci and aberrant alternative splicing in immortal muscle cells. Moreover, immortal hSkMCs displayed attractive additional features such as structural maturation of sarcomeres, persistence of Pax7-positive cells during differentiation and complete disappearance of nuclear foci following (CAG)7 antisense oligonucleotide (ASO) treatment. Overall, the CCND1, CDK4 and TERT immortalization yields versatile, reliable and extremely useful human muscle cell models to investigate the basic molecular features of human muscle cell biology, to elucidate the molecular pathogenetic mechanisms and to test new therapeutic approaches for DM1 in vitro. PMID- 26905646 TI - Electrical activity of ON and OFF retinal ganglion cells: a modelling study. AB - OBJECTIVE: Retinal ganglion cells (RGCs) demonstrate a large range of variation in their ionic channel properties and morphologies. Cell-specific properties are responsible for the unique way RGCs process synaptic inputs, as well as artificial electrical signals such as that from a visual prosthesis. A cell specific computational modelling approach allows us to examine the functional significance of regional membrane channel expression and cell morphology. APPROACH: In this study, an existing RGC ionic model was extended by including a hyperpolarization activated non-selective cationic current as well as a T-type calcium current identified in recent experimental findings. Biophysically-defined model parameters were simultaneously optimized against multiple experimental recordings from ON and OFF RGCs. MAIN RESULTS: With well-defined cell-specific model parameters and the incorporation of detailed cell morphologies, these models were able to closely reconstruct and predict ON and OFF RGC response properties recorded experimentally. SIGNIFICANCE: The resulting models were used to study the contribution of different ion channel properties and spatial structure of neurons to RGC activation. The techniques of this study are generally applicable to other excitable cell models, increasing the utility of theoretical models in accurately predicting the response of real biological neurons. PMID- 26905647 TI - Explanatory pluralism: An unrewarding prediction error for free energy theorists. AB - Courtesy of its free energy formulation, the hierarchical predictive processing theory of the brain (PTB) is often claimed to be a grand unifying theory. To test this claim, we examine a central case: activity of mesocorticolimbic dopaminergic (DA) systems. After reviewing the three most prominent hypotheses of DA activity the anhedonia, incentive salience, and reward prediction error hypotheses-we conclude that the evidence currently vindicates explanatory pluralism. This vindication implies that the grand unifying claims of advocates of PTB are unwarranted. More generally, we suggest that the form of scientific progress in the cognitive sciences is unlikely to be a single overarching grand unifying theory. PMID- 26905648 TI - Mechanochromism in the luminescence of novel cyclometalated platinum(II) complexes with alpha-aminocarboxylates. AB - Six novel phosphorescent cyclometalated platinum(ii) complexes with alpha aminocarboxylato ligands, [Pt(II)(ppy)L] (ppy = 2-phenylpyridinato, L(-) = Gly, Ala, Leu, Ile, Phe, Sar), were synthesized, and the structures were determined by X-ray crystallography. [Pt(II)(ppy)L] (L(-) = Gly, Ala) in crystals are in monomeric structures and stack through pi-pi interactions to form columns, and the features of the luminescence are similar to each other and those in solution, suggesting little influence of the pi-pi interactions on the luminescence. [Pt(II)(ppy)Leu] has a dimeric structure through the Pt-Pt interaction. [Pt(II)(ppy)Sar] showed two pseudo-polymorphs, one of which contains both monomeric and dimeric forms, while the other consists of only dimeric units. Intra-dimer pi-pi interactions were observed in both the dimeric units. [Pt(II)(ppy)L] (L(-) = Leu, Ile, Phe) in the solid state displayed different spectral patterns of luminescence from those in solution, suggesting that the dimeric structures through the Pt-Pt interaction in the solid state are dissociated into the corresponding monomeric ones in solution. The complexes except [Pt(II)(ppy)Phe] in the solid state exhibited reversible luminescent mechanochromism in response to the mechanical grinding and treatment with a few drops of solvent. These phenomena are induced by the change in the energy level of the triplet state due to the change in the extent of intermolecular interactions, which appeared due to the crystalline-amorphous phase conversion. PMID- 26905649 TI - Coordination and insertion of alkenes and alkynes in Au(III) complexes: nature of the intermediates from a computational perspective. AB - The contribution of Au(III) species to catalysis is still debated due to the limited number of characterized intermediates with this oxidation state. In particular, the coordination of alkenes and alkynes to Au(III) followed by insertion into Au(III)-X bonds has been suggested but rarely proven experimentally. Here, these reactions are explored by means of DFT and CCSD(T) calculations considering [AuX3(L)] and [AuX2(L)2](+) complexes. In these complexes, L = ethylene and acetylene have been chosen as substrates of high interest and representative of any unsaturated organic substrate, whereas X is Cl, Me or H, as found in metal salts and as model for intermediates involved in catalysis. Isoelectronic Pt(II) complexes are also considered for comparison. Ethylene coordination occurs preferentially perpendicular for all X except H, whereas for acetylene, coordination takes place in-plane for all X except Cl. These coordination isomers can represent either minima (intermediates) or saddle points (transition states) on the potential energy surface, depending on X. NBO analysis shows how this variety of structures results from the combination of electronic (M-L donation and back-donation) and steric (cis L-X repulsion) effects. With the sole exception of [AuMe2(ethylene)2](+), rotation of the unsaturated ligand and insertion into a cis Au-X bond involve low to moderate energy barriers, DeltaG(?) = 2.5 to 23.5 kcal mol(-1), and are thermodynamically feasible, DeltaG = 4.3 to -47.2 kcal mol(-1). The paucity of experimental observations for such reactions should thus be caused by other factors, like the participation of the intermediates and products in competitive side reactions including the reductive elimination of XCHnCHnX (n = 1 or 2). PMID- 26905651 TI - TOR Signaling and Nutrient Sensing. AB - All living organisms rely on nutrients to sustain cell metabolism and energy production, which in turn need to be adjusted based on available resources. The evolutionarily conserved target of rapamycin (TOR) protein kinase is a central regulatory hub that connects environmental information about the quantity and quality of nutrients to developmental and metabolic processes in order to maintain cellular homeostasis. TOR is activated by both nitrogen and carbon metabolites and promotes energy-consuming processes such as cell division, mRNA translation, and anabolism in times of abundance while repressing nutrient remobilization through autophagy. In animals and yeasts, TOR acts antagonistically to the starvation-induced AMP-activated kinase (AMPK)/sucrose nonfermenting 1 (Snf1) kinase, called Snf1-related kinase 1 (SnRK1) in plants. This review summarizes the immense knowledge on the relationship between TOR signaling and nutrients in nonphotosynthetic organisms and presents recent findings in plants that illuminate the crucial role of this pathway in conveying nutrient-derived signals and regulating many aspects of metabolism and growth. PMID- 26905650 TI - The RNA-binding protein quaking maintains endothelial barrier function and affects VE-cadherin and beta-catenin protein expression. AB - Proper regulation of endothelial cell-cell contacts is essential for physiological functioning of the endothelium. Interendothelial junctions are actively involved in the control of vascular leakage, leukocyte diapedesis, and the initiation and progression of angiogenesis. We found that the RNA-binding protein quaking is highly expressed by endothelial cells, and that its expression was augmented by prolonged culture under laminar flow and the transcription factor KLF2 binding to the promoter. Moreover, we demonstrated that quaking directly binds to the mRNA of VE-cadherin and beta-catenin and can induce mRNA translation mediated by the 3'UTR of these genes. Reduced quaking levels attenuated VE-cadherin and beta-catenin expression and endothelial barrier function in vitro and resulted in increased bradykinin-induced vascular leakage in vivo. Taken together, we report that quaking is essential in maintaining endothelial barrier function. Our results provide novel insight into the importance of post-transcriptional regulation in controlling vascular integrity. PMID- 26905652 TI - Staying Tight: Plasmodesmal Membrane Contact Sites and the Control of Cell-to Cell Connectivity in Plants. AB - Multicellularity differs in plants and animals in that the cytoplasm, plasma membrane, and endomembrane of plants are connected between cells through plasmodesmal pores. Plasmodesmata (PDs) are essential for plant life and serve as conduits for the transport of proteins, small RNAs, hormones, and metabolites during developmental and defense signaling. They are also the only pathways available for viruses to spread within plant hosts. The membrane organization of PDs is unique, characterized by the close apposition of the endoplasmic reticulum and the plasma membrane and spoke-like filamentous structures linking the two membranes, which define PDs as membrane contact sites (MCSs). This specialized membrane arrangement is likely critical for PD function. Here, we review how PDs govern developmental and defensive signaling in plants, compare them with other types of MCSs, and discuss in detail the potential functional significance of the MCS nature of PDs. PMID- 26905653 TI - Light-Mediated Hormonal Regulation of Plant Growth and Development. AB - Light is crucial for plant life, and perception of the light environment dictates plant growth, morphology, and developmental changes. Such adjustments in growth and development in response to light conditions are often established through changes in hormone levels and signaling. This review discusses examples of light regulated processes throughout a plant's life cycle for which it is known how light signals lead to hormonal regulation. Light acts as an important developmental switch in germination, photomorphogenesis, and transition to flowering, and light cues are essential to ensure light capture through architectural changes during phototropism and the shade avoidance response. In describing well-established links between light perception and hormonal changes, we aim to give insight into the mechanisms that enable plants to thrive in variable light environments. PMID- 26905654 TI - Transcriptional Responses to the Auxin Hormone. AB - Auxin is arguably the most important signaling molecule in plants, and the last few decades have seen remarkable breakthroughs in understanding its production, transport, and perception. Recent investigations have focused on transcriptional responses to auxin, providing novel insight into the functions of the domains of key transcription regulators in responses to the hormonal cue and prominently implicating chromatin regulation in these responses. In addition, studies are beginning to identify direct targets of the auxin-responsive transcription factors that underlie auxin modulation of development. Mechanisms to tune the response to different auxin levels are emerging, as are first insights into how this single hormone can trigger diverse responses. Key unanswered questions center on the mechanism for auxin-directed transcriptional repression and the identity of additional determinants of auxin response specificity. Much of what has been learned in model plants holds true in other species, including the earliest land plants. PMID- 26905655 TI - Antibody Production in Plants and Green Algae. AB - Monoclonal antibodies (mAbs) have a wide range of modern applications, including research, diagnostic, therapeutic, and industrial uses. Market demand for mAbs is high and continues to grow. Although mammalian systems, which currently dominate the biomanufacturing industry, produce effective and safe recombinant mAbs, they have a limited manufacturing capacity and high costs. Bacteria, yeast, and insect cell systems are highly scalable and cost effective but vary in their ability to produce appropriate posttranslationally modified mAbs. Plants and green algae are emerging as promising production platforms because of their time and cost efficiencies, scalability, lack of mammalian pathogens, and eukaryotic posttranslational protein modification machinery. So far, plant- and algae derived mAbs have been produced predominantly as candidate therapeutics for infectious diseases and cancer. These candidates have been extensively evaluated in animal models, and some have shown efficacy in clinical trials. Here, we review ongoing efforts to advance the production of mAbs in plants and algae. PMID- 26905656 TI - Environmental Control of Root System Biology. AB - The plant root system traverses one of the most complex environments on earth. Understanding how roots support plant life on land requires knowing how soil properties affect the availability of nutrients and water and how roots manipulate the soil environment to optimize acquisition of these resources. Imaging of roots in soil allows the integrated analysis and modeling of environmental interactions occurring at micro- to macroscales. Advances in phenotyping of root systems is driving innovation in cross-platform-compatible methods for data analysis. Root systems acclimate to the environment through architectural changes that act at the root-type level as well as through tissue specific changes that affect the metabolic needs of the root and the efficiency of nutrient uptake. A molecular understanding of the signaling mechanisms that guide local and systemic signaling is providing insight into the regulatory logic of environmental responses and has identified points where crosstalk between pathways occurs. PMID- 26905658 TI - Adapting environmental function analysis for management of protected areas in small islands--case of Pico Island (the Azores). AB - Protected areas (PAs) are considered key priorities for ensuring long-term sustainability of small islands. The traditional approach of conservation versus development is currently being replaced by an approach of "win-win" relationships. During the last decades PAs have been increasingly requested to simultaneously ensure biodiversity conservation, mainstream ecosystem services into main development policies, and accounting for leisure-related revenues to sustain local and regional economies. Following this new paradigm, the Smartparks project (Planning and Management System for Small Islands Protected Areas), encompassing this study, aimed at an innovative approach for supporting the management of PAs in small islands. In this study, we propose a methodology based on Environmental Functional Analyses (EFA) to compare the potential for conservation and the potential for use of PAs that can be used not only on small islands but also in other territories. For this purpose, a set of environmental and socio-economic components was defined and selected indicators describing each component to calculate conservation and use/development functions of PAs were established. Pico Island, in the Azores archipelago (Portugal), was selected as the case study for testing the methodology. The EFA for all PAs of Pico Island was performed identifying those with more potential for conservation or for development of human activities, and also those with high levels of conflict. A total of 34 indicators was applied (assigning a value from 1 to 3) to the 22 PAs composing the INP of Pico Island: 44% were scored with a value of 1, in both ecological and social components; 22% and 29% were scored 3 in ecological and social components respectively. Social indicators were generally considered less important than environmental ones. In general, PAs presented higher values for conservation. The results further show that the potential for conservation and/or development was consistent with the IUCN category and the objectives assigned to each PA at the time of its classification. However, most PAs are located in the conflict zone of the EFA matrix, revealing a high interaction between PAs conservation objectives and human activities, which brings concern to decision makers and PAs managers. Despite several limitations, the method allowed the performances of PAs to be compared, providing a suitable tool to support rapid assessments and monitoring of PA networks in small islands. The adaptation of the EFA to the PA domain traces a new path for estimating the multiple values of PAs and it may contribute to improve PA management and decision-making. The method could be further included as part of scenario exercise and adaptive management, supporting the prediction of the future evolution of PAs and assessing their potential for conservation in the future throughout the proposed indicators. Thus, the methodology is not exclusive for small islands contexts and, with necessary adaptations and rescaling, it could be a powerful tool in PAs network management worldwide. PMID- 26905657 TI - Chemical Genetics Reveals Environment-Specific Roles for Quorum Sensing Circuits in Pseudomonas aeruginosa. AB - Nutritional cues differentially influence the activities of the three quorum sensing (QS) circuits-Las, Rhl, and Pqs-in the pathogen Pseudomonas aeruginosa. A full understanding of how these systems work together to tune virulence factor production to the environment is lacking. Here, we used chemical probes to evaluate the contribution of each QS circuit to virulence in wild-type P. aeruginosa under defined environmental conditions. Our results indicate that Rhl and Pqs drive virulence factor production in phosphate- and iron-limiting environments, while Las has a minor influence. Consequently, simultaneous inhibition of Rhl and Pqs can attenuate virulence in environments where Las inhibition fails. The activity trends generated in this study can be extrapolated to predict QS inhibitor activity in infection-relevant environments, such as cystic fibrosis sputum. These results indicate that environmental signals can drastically alter the efficacy of small-molecule QS inhibitors in P. aeruginosa and possibly other pathogens. PMID- 26905659 TI - Biofilm formation by Candida albicans and Streptococcus mutans in the presence of farnesol: a quantitative evaluation. AB - The aim of this study was to evaluate the effect of the QS molecule farnesol on single and mixed species biofilms formed by Candida albicans and Streptococcus mutans. The anti-biofilm effect of farnesol was assessed through total biomass quantification, counting of colony forming units (CFUs) and evaluation of metabolic activity. Biofilms were also analyzed by scanning electron microscopy (SEM). It was observed that farnesol reduced the formation of single and mixed biofilms, with significant reductions of 37% to 90% and 64% to 96%, respectively, for total biomass and metabolic activity. Regarding cell viability, farnesol treatment promoted significant log reductions in the number of CFUs, ie 1.3-4.2 log10 and 0.67-5.32 log10, respectively, for single and mixed species biofilms. SEM images confirmed these results, showing decreases in the number of cells in all biofilms. In conclusion, these findings highlight the role of farnesol as an alternative agent with the potential to reduce the formation of pathogenic biofilms. PMID- 26905661 TI - Past Forward: Nostalgia as a Motivational Force. AB - Nostalgia has endured a negative reputation, being branded an unhealthy preoccupation with one's past. This reputation is unwarranted. Nostalgia has remarkable implications for one's future. It strengthens approach orientation, raises optimism, evokes inspiration, boosts creativity, and kindles prosociality. Far from reflecting escapism from the present, nostalgia potentiates an attainable future. PMID- 26905662 TI - Test and validation of methods to sample and detect human virus from environmental surfaces using norovirus as a model virus. AB - BACKGROUND: Viruses cause a major proportion of human infections, especially gastroenteritis and respiratory infections in children and adults. Indirect transmission between humans via environmental surfaces may play a role in infections, but methods to investigate this have been sparse. AIM: To validate and test efficient and reliable procedures to detect multiple human pathogenic viruses on surfaces. METHODS: The study was divided into two parts. In Part A, six combinations of three different swabs (consisting of cotton, foamed cotton, or polyester head) and two different elution methods (direct lysis or immersion in alkaline glycine buffer before lysis) were tested for efficient recovery of human norovirus GII.7 and mengovirus from artificially contaminated surfaces. In Part B we determined the detection limit for norovirus GI.1 and GII.3 using the best procedure found in Part A linked with a commercial multiplex real-time quantitative polymerase chain reaction detection assay. FINDINGS: Combining the polyester swab with direct lysis allowed recovery down to 100 and 10 genome copies/cm(2) of norovirus GI.1 and GII.3, respectively. This procedure resulted in the significant highest recovery of both norovirus and mengovirus, whereas no differences in amplification efficiencies were observed between the different procedures. CONCLUSION: The results indicate that it is possible to detect low concentrations of virus on environmental surfaces. We therefore suggest that a polyester swab, followed by direct lysis, combined with a multiplex qPCR detection assay is an efficient screening tool that merits study of different respiratory and gastrointestinal viruses on environment surfaces. PMID- 26905664 TI - Alternative stethoscope decontamination methods: old practices die hard. PMID- 26905663 TI - Considerations and difficulties of stethoscope disinfection for a motivated healthcare worker. PMID- 26905665 TI - Clinical risk scoring system for predicting extended-spectrum beta-lactamase producing Escherichia coli infection in hospitalized patients. AB - BACKGROUND: Extended spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) has important implications for infection control and empiric antibiotic prescribing. This study aims to develop a risk scoring system for predicting ESBL EC infection based on local epidemiology. METHODS: The study retrospectively collected eligible patients with a positive culture for E. coli during 2011 to 2014. The risk scoring system was developed using variables independently associated with ESBL-EC infection through logistic regression-based prediction. Area under the receiver-operator characteristic curve (AuROC) was determined to confirm the prediction power of the model. FINDINGS: Predictors for ESBL-EC infection were male gender [odds ratio (OR): 1.53], age >=55 years (OR: 1.50), healthcare-associated infection (OR: 3.21), hospital-acquired infection (OR: 2.28), sepsis (OR: 1.79), prolonged hospitalization (OR: 1.88), history of ESBL infection within one year (OR: 7.88), prior use of broad-spectrum cephalosporins within three months (OR: 12.92), and prior use of other antibiotics within three months (OR: 2.14). Points scored ranged from 0 to 47, and were divided into three groups based on diagnostic performance parameters: low risk (score: 0-8; 44.57%), moderate risk (score: 9-11; 21.85%) and high risk (score: >=12; 33.58%). The model displayed moderate power of prediction (AuROC: 0.773; 95% confidence interval: 0.742-0.805) and good calibration (Hosmer-Lemeshow chi(2) = 13.29; P = 0.065). CONCLUSION: This tool may optimize the prescribing of empirical antibiotic therapy, minimize time to identify patients, and prevent spreading of ESBL-EC. Prior to adoption into routine clinical practice, further validation study of the tool is needed. PMID- 26905666 TI - Microbiology service centralization: a step too far? PMID- 26905667 TI - Investigating ward-based transmission of alert organisms - infection control down the drain? PMID- 26905668 TI - The liability risks of naloxone access expansion should be the least of our worries. PMID- 26905669 TI - The subjective value of probabilistic outcomes: Impact of reward magnitude on choice with uncertain rewards in rats. AB - Interest is rising for animal modelling of Gambling disorder (GD), which is rapidly emerging as a mental health concern. In the present study, we assessed gambling proneness in male Wistar-Han rats using the "Probabilistic Delivery Task" (PDT). This operant protocol is based on choice between either certain, small amounts of food (SS) or larger amounts of food (LLL) delivered (or not) depending on a given (and progressively decreasing) probability. Here, we manipulated the ratio between large and small reward size to assess the impact of different magnitudes on rats' performance. Specifically, we drew a comparison between threefold (2 vs 6 pellets) and fivefold (1 vs 5 pellets) sizes. As a consequence, the "indifferent point" (IP, at which either choice is mathematically equivalent in terms of total foraging) was at 33% and 20% probability of delivery, respectively. Animals tested with the sharper contrast (i.e. fivefold ratio) exhibited sustained preference for LLL far beyond the IP, despite high uncertainty and low payoff, which rendered LLL a sub-optimal option. By contrast, animals facing a slighter contrast (i.e. threefold ratio) were increasingly disturbed by progressive rarefaction of rewards, as expressed by enhanced inadequate nose-poking: this was in accordance with their prompt shift in preference to SS, already shown around the IP. In conclusion, a five-folded LLL-to-SS ratio was not only more attractive, but also less frustrating than a three-folded one. Thus, a profile of gambling proneness in the PDT is more effectively induced by marked contrast between alternative options. PMID- 26905670 TI - E2F1-CDK1 pathway activation in kanamycin-induced spiral ganglion cell apoptosis and the protective effect of CR8. AB - Cochlear hair cell loss results in the secondary loss of spiral ganglion cells (SGCs). The death of these SGCs is due to apoptosis. The E2F1-cyclin dependent kinase 1 (CDK1) pathway is believed to represent an important mechanism of neuronal cell death. However, the role of this pathway in spiral ganglion neuronal apoptosis has not yet been reported. In this study, we deafened guinea pigs with a subcutaneous injection of kanamycin followed by an intravenous infusion of furosemide and then assayed the expression levels of cleaved caspase 3, E2F1, CDK1 and cleaved caspase-9 during the induced SGC apoptosis. Our results revealed that co-administration of kanamycin and furosemide rapidly induced hair cell loss in the guinea pigs and then resulted in a progressive loss of SGCs. Expression levels of E2F1 and CDK1 were obviously up-regulated at 1 and 3 days after deafening. Cleaved caspase-9 also increased robustly 1 or 2 weeks after the deafening procedure. The up-regulation of E2F1, CDK1 and cleaved caspase-9 was significantly attenuated by the systemic injection of CR8 (1mg/kg/day, intraperitoneally) starting at 5min after deafening. These findings indicate that the activation of the E2F1-CDK1 pathway and cell cycle re-entry contributes to the apoptosis of SGCs and that the selective inhibition of this signaling cascade may represent an attractive therapeutic strategy. CR8 has the potential to protect SGCs from apoptosis. PMID- 26905671 TI - Coil-like Enzymatic Biohybrid Structures Fabricated by Rational Design: Controlling Size and Enzyme Activity over Sequential Nanoparticle Bioconjugation and Filtration Steps. AB - Well-defined enzymatic biohybrid structures (BHS) composed of avidin, biotinylated poly(propyleneimine) glycodendrimers, and biotinylated horseradish peroxidase were fabricated by a sequential polyassociation reaction to adopt directed enzyme prodrug therapy to protein-glycopolymer BHS for potential biomedical applications. To tailor and gain fundamental insight into pivotal properties such as size and molar mass of these BHS, the dependence on the fabrication sequence was probed and thoroughly investigated by several complementary methods (e.g., UV/vis, DLS, cryoTEM, AF4-LS). Subsequent purification by hollow fiber filtration allowed us to obtain highly pure and well defined BHS. Overall, by rational design and control of preparation parameters, e.g., fabrication sequence, ligand-receptor stoichiometry, and degree of biotinylation, well-defined BHS with stable and even strongly enhanced enzymatic activities can be achieved. Open coil-like structures of BHS with few branches are available by the sequential bioconjugation approach between synthetic and biological macromolecules possessing similar size dimensions. PMID- 26905672 TI - Prognostic Indicators of Persistent Post-Concussive Symptoms after Deployment Related Mild Traumatic Brain Injury: A Prospective Longitudinal Study in U.S. Army Soldiers. AB - Mild traumatic brain injury (mTBI), or concussion, is prevalent in the military. The course of recovery can be highly variable. This study investigates whether deployment-acquired mTBI is associated with subsequent presence and severity of post-concussive symptoms (PCS) and identifies predictors of persistent PCS among US Army personnel who sustained mTBI while deployed to Afghanistan. We used data from a prospective longitudinal survey of soldiers assessed 1-2 months before a 10-month deployment to Afghanistan (T0), on redeployment to the United States (T1), approximately 3 months later (T2), and approximately 9 months later (T3). Outcomes of interest were PCS at T2 and T3. Predictors considered were: sociodemographic factors, number of previous deployments, pre-deployment mental health and TBI history, and mTBI and other military-related stress during the index deployment. The study sample comprised 4518 soldiers, 822 (18.2%) of whom experienced mTBI during the index deployment. After adjusting for demographic, clinical, and deployment-related factors, deployment-acquired mTBI was associated with nearly triple the risk of reporting any PCS and with increased severity of PCS when symptoms were present. Among those who sustained mTBI, severity of PCS at follow-up was associated with history of pre-deployment TBI(s), pre-deployment psychological distress, more severe deployment stress, and loss of consciousness or lapse of memory (versus being "dazed" only) as a result of deployment-acquired mTBI. In summary, we found that sustaining mTBI increases risk for persistent PCS. Previous TBI(s), pre-deployment psychological distress, severe deployment stress, and loss of consciousness or lapse of memory resulting from mTBI(s) are prognostic indicators of persistent PCS after an index mTBI. These observations may have actionable implications for prevention of chronic sequelae of mTBI in the military and other settings. PMID- 26905673 TI - LC-MS/MS and volumetric absorptive microsampling for quantitative bioanalysis of cathinone analogues in dried urine, plasma and oral fluid samples. AB - In the last few years, several cathinone analogues have appeared on the illicit drug market and proposed as an alternative to already known stimulants in several recreational settings. The World Anti-Doping Agency classified the synthetic cathinones in the Prohibited List as specified stimulants, banned in sport competitions. We developed and validated an LC-MS/MS method for the analysis of methylone, ethylone, butylone, mephedrone, 4-methylethcathinone and 3,4 methylenedioxypyrovalerone in dried urine, plasma and oral fluid samples. Volumetric absorptive microsampling has been employed as a miniaturised sampling technique for collecting dried biological samples. Chromatographic analysis was carried out on a C18 reversed phase column with a mobile phase composed of formic acid in a water/acetonitrile mixture, by using a triple quadrupole mass analyzer. The main parameters of the volumetric absorptive microsampling procedure were investigated and the method was fully validated with satisfactory results in terms of linearity, precision, absolute recovery, matrix effects, selectivity and stability. The method was successfully applied to real samples collected from cathinones users. The biosampling strategy via volumetric absorptive microsampling for urine, plasma and oral fluid could provide reliable information, with a future perspective of implementation for forensic cases as well as for sport drug testing. PMID- 26905674 TI - Letter from the Editor. PMID- 26905677 TI - The diversity of pneumococcal conjugate vaccine impact observed through their implementation. PMID- 26905678 TI - The multifaceted impact of pneumococcal conjugate vaccine implementation in children in France between 2001 to 2014. AB - In 2003, France was the first European country to recommend 7-valent pneumococcal conjugate vaccine (PCV7) for a large proportion of healthy children. With complicated recommendations, the vaccine coverage during the first 4 y of implementation was low, then progressively increased to reach 90% in 2008. The aim of this review was to describe the particular impact of PCVs in a country where the vaccine coverage was initially suboptimal. After PCV7 implementation, the PCV7 serotypes nearly disappeared among pneumococci isolated from meningitis (-73%), other invasive pneumococcal disease (IPD; -90%) and pneumococcal carriage (-97%). Consequently, the rates of penicillin-resistant strains declined. However, because of important serotype replacement, the global effect on the incidence of meningitis (-31%) or other IPD (-14%) was modest and observed only in young children < 2 y old. After PCV13 transition, with immediate high vaccine coverage, the vaccine had an important impact on all pneumococcal disease: reduction of -20% for pneumococcal meningitis, -36% for non-meningitis IPD, -32% for community acquired pneumonia and -15% for S. pneumoniae carriage. These findings underline the complexity of pneumococcal epidemiology and the importance of high and fast vaccination coverage to obtain the optimal effect of PCVs. PMID- 26905679 TI - Evaluating the impact of PCV-10 on invasive pneumococcal disease in Brazil: A time-series analysis. AB - Routine infant immunization with 10-valent pneumococcal conjugate vaccine (PCV 10) began in Brazil in 2010. The impact of the PCV-10 on rates of invasive pneumococcal disease (IPD) at the population level was not yet evaluated. Serotype-specific IPD changes after PCV-10 introduction is still to be determined. Data from national surveillance system for notifiable diseases (SINAN) and national reference laboratory for S. pneumoniae in Brazil (IAL) were linked to enhance case ascertainment of IPD. An interrupted time-series analysis was conducted to predict trends in the postvaccination IPD rates in the absence of PCV-10 vaccination, taking into consideration seasonality and secular trends. PCVs serotype-specific distribution were assessed before (2008-2009) and after (2011-2013) the introduction of PCV-10 in the immunization program. A total of 9,827 IPD cases were identified from 2008-2013 when combining SINAN and IAL databases. Overall, PCV-10 types decreased by 41.3% after PCV-10 vaccination period, mostly in children aged 2-23 months, while additional PCV-13 serotypes increased by 62.8% mainly in children under 5-year of age. For children aged 2-23 months, targeted by the immunization program, we observed a 44.2% (95%CI, 15.8 72.5%) reduction in IPD rates. In contrast, significant increase in IPD rates were observed for adults aged 18-39 y (18.9%, 95%CI 1.1-36.7%), 40-64 y (52.5%, 95%CI 24.8-80.3%), and elderly >= 65 y (79.3%, 95%CI 62.1-96.5%). This is the first report of a time-series analysis for PCV impact in IPD conducted at national level data in a developing country. We were able to show significant impact of PCV-10 on IPD for age groups targeted by vaccination in Brazil, 3 y after its introduction. No impact on other age groups was demonstrated. PMID- 26905680 TI - Staphylococcus aureus and Streptococcus pneumoniae interaction and response to pneumococcal vaccination: Myth or reality? AB - S. aureus and S. pneumoniae are both common pathogens that are also carried by a large proportion of healthy individuals in the nasal and nasopharyngeal spaces. A negative association between carriage of S. aureus and S. pneumoniae has been reported in children in various epidemiologic studies from different geographical regions. Most studies found that the negative association between S. pneumoniae and S. aureus was significant only for carriage of vaccine-type S. pneumoniae strains. In this review, we summarize the various suggested mechanisms of this suggested bacterial interference, and the clinical implications reported following PCV introduction to date in various geographical regions. PMID- 26905682 TI - Molecular Design of Ionization-Induced Proton Switching Element Based on Fluorinated DNA Base Pair. AB - To design theoretically the high-performance proton switching element based on DNA base pair, the effects of fluorine substitution on the rate of proton transfer (PT) in the DNA model base pair have been investigated by means of direct ab initio molecular dynamics (AIMD) method. The 2-aminopyridine dimer, (AP)2, was used as the model of the DNA base pair. One of the hydrogen atoms of the AP molecule in the dimer was substituted by a fluorine (F) atom, and the structures of the dimer, expressed by F-(AP)2, were fully optimized at the MP2/6 311++G(d,p) level. The direct AIMD calculations showed that the proton is transferred within the base pair after the vertical ionization. The rates of PT in F-(AP)2(+) were calculated and compared with that of (AP)2(+) without an F atom. It was found that PT rate is accelerated by the F-substitution. Also, the direction of PT between F-AP and AP molecules can be clearly controlled by the position of F-substitution (AP)2 in the dimer. PMID- 26905681 TI - Interim results of an ecological experiment - Conjugate vaccination against the pneumococcus and serotype replacement. AB - Streptococcus pneumoniae has more than 95 serotypes, each of which presumably can cause sepsis, meningitis, pneumonia, and acute otitis media. Pneumococcal conjugate vaccines (PCV) targeted against a limited number of serotypes have nonetheless revealed an impressive impact on each manifestation of pneumococcal disease. At the same time, growing evidence of significant non-vaccine type (NVT) replacement disease following implementation of infant PCV programs has raised questions about the long-term viability of PCV immunization strategies and how to optimize PCV formulations. We discuss here theoretical and practical considerations regarding serotype replacement, and provide a snapshot of the most important NVT types seen to date after implementation of the 2 higher-valent PCVs. PMID- 26905686 TI - Ameliorative effects of pentoxifylline on NOS induced by diabetes in rat kidney. AB - OBJECTIVES: Diabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide. The NO system has been implicated in the pathogenesis of DN. In this study, we aimed to evaluate the healing effect of pentoxifylline on NOS in STZ-induced diabetic rat's kidney. MATERIAL AND METHODS: In this study, 50 Wistar albino male rats were used. The rats were divided into five groups; Group C control; Group D only diabetes; Group D + PI and D + PII diabetes + pentoxifylline; Group P only pentoxifylline. Group DPI rats received just pentoxifylline from the beginning of the experiments. However, Group DPII rats received saline in the first month and 50 mg/kg/day of pentoxifylline for the following month. At the end of two months, NOS expressions in kidney tissue were assessed using qRT-PCR and immunohistochemistry analysis. RESULTS: At the end of the experiments, desquamation of the epithelial cells of the tubules, clear glycogen-filled distal tubules and increased number of apoptotic cells were seen in Group D. Diabetic rats' nNOS immunoreactivity had increased and eNOS and iNOS immunoreactivity had decreased; nNOS, iNOS and eNOS mRNA levels tended to decrease compared to the control group. PTX ameliorated eNOS, iNOS and nNOS protein levels and apoptotic cells, but did not affect mRNA levels. CONCLUSION: In conclusion, PTX has a healing effect on this damage by affecting NOS expression. PMID- 26905687 TI - Antibacterial Azaphilones from an Endophytic Fungus, Colletotrichum sp. BS4. AB - Three new compounds, colletotrichones A-C (1-3), and one known compound, chermesinone B (4a), were isolated from an endophytic fungus, Colletotrichum sp. BS4, harbored in the leaves of Buxus sinica, a well-known boxwood plant used in traditional Chinese medicine (TCM). Their structures were determined by extensive spectroscopic analyses including 1D and 2D NMR, HRMS, ECD spectra, UV, and IR, as well as single-crystal X-ray diffraction, and shown to be azaphilones sharing a 3,6a-dimethyl-9-(2-methylbutanoyl)-9H-furo[2,3-h]isochromene-6,8-dione scaffold. Owing to the remarkable antibacterial potency of known azaphilones coupled to the usage of the host plant in TCM, we evaluated the antibacterial efficacy of the isolated compounds against two commonly dispersed environmental strains of Escherichia coli and Bacillus subtilis, as well as against two human pathogenic clinical strains of Staphylococcus aureus and Pseudomonas aeruginosa. Compound 1 exhibited marked antibacterial potencies against the environmental strains that were comparable to the standard antibiotics. Compound 3 was also active against E. coli. Finally, compound 2a exhibited the same efficacy as streptomycin against the clinically relevant bacterium S. aureus. The in vitro cytotoxicity of these compounds on a human acute monocytic leukemia cell line (THP-1) was also assessed. Our results provide a scientific rationale for further investigations into endophyte-mediated host chemical defense against specialist and generalist pathogens. PMID- 26905689 TI - Choroidal Thickness in Children with Beta Thalassemia Major. AB - PURPOSE: The purpose of this study was to determine whether there are differences in choroidal thickness in children with beta thalassemia major (beta-TM). METHODS: Thirty-five patients with beta-TM and 38 healthy children aged between 3 and 16 years participated in the study. After complete eye examinations were conducted on the participants, choroidal thickness measurements were performed using optical coherence tomography. Correlations between choroidal thickness and laboratory and clinical parameters, such as age, sex, hemoglobin and ferritin levels, duration of disease, type and duration of chelating therapy, visual acuity, intraocular pressure, central corneal thickness, and axial length were also evaluated. RESULTS: The mean ages for the study group and for the control group were 8.2 +/- 2.7 and 7.9 +/- 2.4 years, respectively. There were no statistical differences between groups in terms of visual acuity, intraocular pressure, central corneal thickness, or axial length (p > 0.05). Choroidal thicknesses at the foveal center were 286 +/- 33 MUm in beta-TM patients and 335 +/- 423 MUm in the healthy control children. Choroidal thicknesses at each point within the horizontal nasal and temporal quadrants were thinner in the beta-TM group. There was a positive correlation between choroidal thickness and hemoglobin levels and a negative correlation between choroidal thickness and ferritin levels (r = 0.924, p < 0.001 and r = -0.947, p < 0.001, respectively). There was no correlation between clinical or ocular characteristics and choroidal thickness. CONCLUSIONS: Choroidal thickness was significantly thinner in all quadrants in children with beta-TM. This thinning of the choroid may be the reason for the development of eye disorders in older patients with beta-TM. PMID- 26905688 TI - Serotonin depletion eliminates sex differences with respect to context conditioned immobility in rat. AB - RATIONALE: Previous studies have shown that male rats display more anxiety-like behavior than females as assessed using the elevated plus maze and that serotonin depletion abolishes this difference by exerting an anxiolytic-like effect in males only. OBJECTIVES: To compare male and female rats with respect to immobility and startle responses to sudden noise bursts after contextual fear conditioning and to explore to what extent any possible sex difference in this regard is influenced by serotonin depletion during testing (but not acquisition). RESULTS: In line with previous studies, males displayed more immobility following contextual conditioning induced by previous exposure to foot shocks than females. In males but not females, the immobility response was reduced by administration of the serotonin synthesis inhibitor para-chlorophenylalanine (PCPA) between shock exposure and testing, the consequence being that males and females no longer differed in this regard. Untreated males but not females displayed a negative correlation between fear-conditioned startle and immobility, suggesting that the latter behavior, when excessive, interferes with the former. In line with this assumption, the reduction in immobility following administration of PCPA in males coincided with an increase in startle that was not observed in females, hence revealing a sex difference in startle not seen in untreated controls. CONCLUSION: The greater display of context-conditioned immobility in males compared with females appears to be serotonin-dependent. PMID- 26905690 TI - Time Course of Pupil Center Location after Ocular Drug Application. AB - PURPOSE: To investigate the time course of pupil centration after application of common topical ocular drugs. METHODS: Single drops of 2.5% phenylephrine hydrochloride, 1% tropicamide, and 2% pilocarpine hydrochloride were applied on different days to the right eyes of 12 participants. Anterior eye images were captured, at 5-min intervals for an hour, using an infrared-sensitive camera. The images were analyzed to determine pupil diameter and pupil center, the latter with respect to the limbal center. As a control, natural pupil size and pupil center were determined under different illuminances. RESULTS: Pupil centers of natural pupils shifted temporally as pupils dilated. At common pupil sizes, drug induced pupil centers were different from natural pupil centers. Phenylephrine produced a center shift in the nasal and inferior directions that peaked after a mean of 30 min, whereas dilation was continuing up to 60 min. Tropicamide produced transient center shifts in the nasal and inferior directions that peaked at about 10 min before reducing toward baseline values, whereas dilation reached a peak at about 25 min. Pilocarpine produced a small sustained superior shift that, like constriction, reached a peak after about 25 min. CONCLUSIONS: Application of topical ophthalmic drugs cause shifts in pupil center that do not match those produced by natural changes in pupil size and that, in the cases of phenylephrine and tropicamide, follow a different time course than the pupil size changes. PMID- 26905691 TI - Prevalence of Ocular Anomalies among Schoolchildren in Ashaiman, Ghana. AB - PURPOSE: Information on ocular anomalies can help in developing specific interventions to prevent visual impairment especially among children. The aim of this study was therefore to determine the prevalence, the causes of ocular anomalies, and their impact on vision of schoolchildren in Ghana. METHODS: A cluster random sampling technique was used to select four government primary schools in Ashaiman Municipal for this study. Each pupil underwent ocular examination involving visual acuity, external examination, anterior and posterior segment examination, and objective and subjective refraction. They also answered questions relating to ocular problems affecting them. RESULTS: A total of 811 pupils were sampled, with ages ranging from 6 to 16 years. The mean age of the sampled population was 10.6 years (95% confidence interval, 10.4 to 10.8). Prevalence of ocular anomalies was 27.3% (95% confidence interval, 24.2 to 30.5). Allergic conjunctivitis (17.3%) and refractive errors (6.8%) were the main causes of ocular anomalies. Others include pinguecula (1.2%), pterygia (0.9%), infectious conjunctivitis (0.3%), corneal opacity (0.1%), lens opacity (0.1%), and retinal degeneration (0.1%). Ocular anomalies and refractive errors were significantly associated with sex (p = 0.04 and p = 0.01, respectively). Presenting visual acuity in the better eye 20/40 or worse was identified in 5.3% of schoolchildren, and 0.5% had moderate visual impairment. Only 11.8% of schoolchildren with ocular anomalies had been treated for their ocular problems before the study. CONCLUSIONS: The prevalence and causes of ocular anomalies found in this study suggest a need for more targeted eye health interventions such as school eye screening for early diagnosis and treatment of any presenting conditions among schoolchildren. PMID- 26905692 TI - No link between macrolide antibiotics and ventricular arrhythmias, study finds. PMID- 26905693 TI - Effects of warm ischemia and reperfusion on the liver microcirculatory phenotype of rats: underlying mechanisms and pharmacological therapy. AB - Warm ischemia and reperfusion (WIR) causes hepatic damage and may lead to liver failure, however the mechanisms involved are largely unknown. Here we have characterized the microcirculatory status and endothelial phenotype of livers undergoing WIR, and evaluated the use of simvastatin in WIR injury prevention. Male Wistar rats received simvastatin, or vehicle, 30 min before undergoing 60 min of partial warm ischemia (70%) followed by 2 h or 24 h of reperfusion. Hepatic and systemic hemodynamics, liver injury (AST, ALT, LDH), endothelial function (vasodilatation in response to acetylcholine), KLF2 and nitric oxide pathways, oxidative stress, inflammation (neutrophil and macrophage infiltration) and cell death were evaluated. Profound microcirculatory dysfunction occurred rapidly following WIR. This was evidenced by down-regulation of the KLF2 vasoprotective pathway, impaired vasodilatory capability and endothelial activation, altogether leading to increased hepatic vascular resistance and liver inflammation, with significant leukocyte infiltration, oxidative stress and cell death. Simvastatin preserved the hepatic endothelial phenotype, and blunted the detrimental effects of WIR on liver hemodynamics and organ integrity. In conclusion, WIR-induced injury to liver sinusoidal endothelial cells is mitigated by pre-treatment with Simvastatin probably through a KLF2-dependent mechanism. PMID- 26905695 TI - Valve Interstitial Cells Act in a Pericyte Manner Promoting Angiogensis and Invasion by Valve Endothelial Cells. AB - Neovascularization is an understudied aspect of calcific aortic valve disease (CAVD). Within diseased valves, cells along the neovessels' periphery stain for pericyte markers, but it is unclear whether valvular interstitial cells (VICs) can demonstrate a pericyte-like phenotype. This investigation examined the perivascular potential of VICs to regulate valve endothelial cell (VEC) organization and explored the role of Angiopoeitin1-Tie2 signaling in this process. Porcine VECs and VICs were fluorescently tracked and co-cultured in Matrigel over 7 days. VICs regulated early VEC network organization in a ROCK dependent manner, then guided later VEC network contraction through chemoattraction. Unlike vascular control cells, the valve cell cultures ultimately formed invasive spheroids with 3D angiogenic-like sprouts. VECs co cultured with VICs displayed significantly more invasion than VECs alone; with VICs generally leading and wrapping around VEC invasive sprouts. Lastly, Angiopoietin1-Tie2 signaling was found to regulate valve cell organization during VEC/VIC spheroid formation and invasion. VICs demonstrated pericyte-like behaviors toward VECs throughout sustained co-culture. The change from a vasculogenic network to an invasive sprouting spheroid suggests that both cell types undergo phenotypic changes during long-term culture in the model angiogenic environment. Valve cells organizing into spheroids and undergoing 3D invasion of Matrigel demonstrated several typical angiogenic-like phenotypes dependent on basal levels of Angiopoeitin1-Tie2 signaling and ROCK activation. These results suggest that the ectopic sustained angiogenic environment during the early stages of valve disease promotes organized activity by both VECs and VICs, contributing to neovessel formation and the progression of CAVD. PMID- 26905696 TI - Mesh Excision: Is Total Mesh Excision Necessary? AB - Nearly 29% of women will undergo a secondary, repeat operation for pelvic organ prolapse (POP) symptom recurrence following a primary repair, as reported by Abbott et al. (Am J Obstet Gynecol 210:163.e1-163.e1, 2014). In efforts to decrease the rates of failure, graft materials have been utilized to augment transvaginal repairs. Following the success of using polypropylene mesh (PPM) for stress urinary incontinence (SUI), the use of PPM in the transvaginal repair of POP increased. However, in recent years, significant concerns have been raised about the safety of PPM mesh. Complications, some specific to mesh, such as exposures, erosion, dyspareunia, and pelvic pain, have been reported with increased frequency. In the current literature, there is not substantive evidence to suggest that PPM has intrinsic properties that warrant total mesh removal in the absence of complications. There are a number of complications that can occur after transvaginal mesh placement that do warrant surgical intervention after failure of conservative therapy. In aggregate, there are no high-quality controlled studies that clearly demonstrate that total mesh removal is consistently more likely to achieve pain reduction. In the cases of obstruction and erosion, it seems clear that definitive removal of the offending mesh is associated with resolution of symptoms in the majority of cases and reasonable practice. There are a number of complications that can occur with removal of mesh, and patients should be informed of this as they formulate a choice of treatment. We will review these considerations as we examine the clinical question of whether total versus partial removal of mesh is necessary for the resolution of complications following transvaginal mesh placement. PMID- 26905694 TI - FAT1 mutations cause a glomerulotubular nephropathy. AB - Steroid-resistant nephrotic syndrome (SRNS) causes 15% of chronic kidney disease (CKD). Here we show that recessive mutations in FAT1 cause a distinct renal disease entity in four families with a combination of SRNS, tubular ectasia, haematuria and facultative neurological involvement. Loss of FAT1 results in decreased cell adhesion and migration in fibroblasts and podocytes and the decreased migration is partially reversed by a RAC1/CDC42 activator. Podocyte specific deletion of Fat1 in mice induces abnormal glomerular filtration barrier development, leading to podocyte foot process effacement. Knockdown of Fat1 in renal tubular cells reduces migration, decreases active RAC1 and CDC42, and induces defects in lumen formation. Knockdown of fat1 in zebrafish causes pronephric cysts, which is partially rescued by RAC1/CDC42 activators, confirming a role of the two small GTPases in the pathogenesis. These findings provide new insights into the pathogenesis of SRNS and tubulopathy, linking FAT1 and RAC1/CDC42 to podocyte and tubular cell function. PMID- 26905698 TI - Enhancement of accelerated carbonation of alkaline waste residues by ultrasound. AB - The continuous growth of anthropogenic CO2 emissions into the atmosphere and the disposal of hazardous wastes into landfills present serious economic and environmental issues. Reaction of CO2 with alkaline residues or cementitius materials, known as accelerated carbonation, occurs rapidly under ambient temperature and pressure and is a proven and effective process of sequestering the gas. Moreover, further improvement of the reaction efficiency would increase the amount of CO2 that could be permanently sequestered into solid products. This paper examines the potential of enhancing the accelerated carbonation of air pollution control residues, cement bypass dust and ladle slag by applying ultrasound at various water-to-solid (w/s) ratios. Experimental results showed that application of ultrasound increased the CO2 uptake by up to four times at high w/s ratios, whereas the reactivity at low water content showed little change compared with controls. Upon sonication, the particle size of the waste residues decreased and the amount of calcite precipitates increased. Finally, the sonicated particles exhibited a rounded morphology when observed by scanning electron microscopy. PMID- 26905697 TI - Comparison of Ga-68-Labeled Fusarinine C-Based Multivalent RGD Conjugates and [(68)Ga]NODAGA-RGD-In Vivo Imaging Studies in Human Xenograft Tumors. AB - PURPOSE: Multimeric arginine-glycine-aspartic acid (RGD) peptides have advantages for imaging integrin alphavbeta3 expression. Here, we compared the in vitro and in vivo behavior of three different Ga-68-labeled multimeric Fusarinine C-RGD (FSC-RGD) conjugates, whereby RGD was coupled directly, via a succinic acid or PEG linker (FSC(RGDfE)3, FSC(succ-RGD)3, FSC(Mal-RGD)3). The positron emission tomography/X-ray computed tomography (PET/CT) imaging properties were further compared using [(68)Ga]FSC(succ-RGD)3 with the monomeric [(68)Ga]NODAGA-RGD in a murine tumor model. PROCEDURE: FSC-RGD conjugates were labeled with Ga-68, and stability properties were studied. For in vitro characterization, the partition coefficient, integrin alphavbeta3 binding affinity, and cell uptake were determined. To characterize the in vivo properties, biodistribution studies and microPET/CT were carried out using mice bearing either human M21/M21-L melanoma or human U87MG glioblastoma tumor xenografts. RESULTS: All FSC-RGD conjugates were quantitatively labeled with Ga-68 within 10 min at RT. The [(68)Ga]FSC-RGD conjugates exhibited high stability and hydrophilic character, with only minor differences between the different conjugates. In vitro and in vivo studies showed enhanced integrin alphavbeta3 binding affinity, receptor-selective tumor uptake, and rapid renal excretion resulting in good imaging properties. CONCLUSIONS: The type of linker between FSC and RGD had no pronounced effect on targeting properties of [(68)Ga]FSC-RGD trimers. In particular, [(68)Ga]FSC(succ-RGD)3 exhibited improved properties compared to [(68)Ga]NODAGA-RGD, making it an alternative for imaging integrin alphavbeta3 expression. PMID- 26905700 TI - Association between Helicobacter Pylori and Gastric Cancer. AB - INTRODUCTION: A casual relation has been thought to exist between Helicobacter pylori infection and gastric cancer. The present study was carried out to find correlation between H. pylori and gastric carcinogenesis. METHODS: A case control study was performed in the department of endoscopy, Tribhuvan University Teaching Hospital, between January 2008 and February 2009. All patients having carcinoma stomach on endoscopic evaluation later confirmed by histopathological examination were included. Total 50 healthy individuals, with no positive finding in endoscopy were included in control group. RESULTS: Total 37 cases were analyzed. There were 23 (62.2%) males and 14 (37.8%) females. Majority were above 60 years (46%). Blood group A was commonest group found in patients with carcinoma stomach. Distal part, antrum, 20 (54%) was commonest location of tumor and Borrmann type three was commonest endoscopic type of tumor presentation. Majority of patients received triple therapy and H. pylori detection was low in those treated with triple therapy. Distal tumors were significantly associated with increased prevalence of H. pylori positivity. Total incidence of H. pylori in cases was 54% (20/37). In 15 (75%) cases, H. pylori could be detected by both ELISA and biopsy method. Incidence of H. pylori in controls was 64% (32/50). There was no statistically significant difference in H. pylori presence in cases and control. CONCLUSIONS: Our study couldn't establish association between H. pylori and gastric cancer. More prospective trials can help find out correlation between combination of risk factors and gastric cancer. PMID- 26905701 TI - Higher Incision at Upper Part of Lower Segment Caesarean Section. AB - INTRODUCTION: To determine if the upper part of the lower segment of the uterus is a better site for cesarean incision then the traditionally used lower end. METHODS: This is a case-control study (1:1 ratio) conducted from 1(st) October 2012- 30(th) September 2013 observed between transverse incision at the upper part of the lower segment versus traditional lower segment of the uterus. Two hundred caesarean sections were performed via a transverse uterine incision at the upper part of the lower segment and equal numbers of uterine incision was performed at traditional lower segment. To obtain less intraoperative bleeding high incision made at thicker wider muscular part at of the upper part of lower segment about 2-3 cm distances from vesico-uterine serosa. RESULTS: The estimated volume of blood loss in high incision 188+/-60.1 ml was significantly less compared to traditional incision 330.1+/- 86.5 ml (p<0.05). Duration of operation 30.5+/- 6.6 minute versus 45.3+/-7.2 minute and tearing the uterine incision was significantly less with the high incision versus traditional incision. Other procedural and patient benefits are noted. CONCLUSIONS: An incision at the upper part of the lower segment reduces blood loss, enhances uterine retraction, predisposes to fewer complications, is easier to repair, precludes bladder adhesion to the suture line and reduces operation time. PMID- 26905699 TI - Antithrombotic and antiplatelet activities of small-molecule alkaloids from Scolopendra subspinipes mutilans. AB - The aim of this study was to discover small-molecule anticoagulants from Scolopendra subspinipes mutilans (SSM). A new acylated polyamine (1) and a new sulfated quinoline alkaloid (2) were isolated from SSM. Treatment with the new alkaloids 1, 2, and indole acetic acid 4 prolonged the activated partial thromboplastin time and prothrombin time and inhibited the activity and production of thrombin and activated factor X. Furthermore, compounds 1, 2, and 4 inhibited thrombin-catalyzed fibrin polymerization and platelet aggregation. In accordance with these potential in vitro antiplatelet activities, compounds 1, 2, and 4 showed enhanced antithrombotic effects in an in vivo pulmonary embolism and arterial thrombosis model. Compounds 1, 2, and 4 also elicited anticoagulant effects in mice. Collectively, this study may serve as the groundwork for commercializing SSM or compounds 1, 2, and 4 as functional food components for the prevention and treatment of pathogenic conditions and serve as new scaffolds for the development of anticoagulants. PMID- 26905702 TI - Hypertension in Primary Open Angle Glaucoma. AB - INTRODUCTION: The impact of vascular factors in POAG is well known and controversial. Some reports have shown high blood pressure in POAG, some low systolic blood pressure and some described no difference in blood pressure between POAG and controls. However decreased ocular perfusion pressure was found in most of the studies. Our study aims to assess the role of hypertension in POAG . METHODS: It was cross-sectional case-control hospital based study carried out from 1st June 2012 to 1st June 2013. There were 40 cases and 100 controls included in the study. The role of hypertension were compared with those hypertensive patients with glaucoma (cases) and hypertensive patients without glaucoma (controls). RESULTS: Age above 50 years (odds ratio: 4.827 with 95% CI 1.862-12.517), male genders (odds ratio: 3.10 with 95% CI 1.356-7.146) and low diastolic perfusion pressure (odds ratio: 3.857 with 95% CI 1.362-11.224) showed strongly positive association with POAG. High systolic blood pressure (odds ratio: 1.476 95% CI 0.627-3.476), high diastolic blood pressure (odds ratio: 1.348 95% CI 0.587-3.096) and low systolic perfusion pressure (odds ratio: 1.8661 with 95% CI 0.649- 5.335) were weakly associated with glaucoma in our study. CONCLUSIONS: Age above 50 years, male gender and low diastolic perfusion pressure were strong risk factor for the development of POAG. PMID- 26905703 TI - Lignocaine and Esmolol on Stress Response to Laryngoscopy and Intubation. AB - INTRODUCTION: Laryngoscopy and tracheal intubation causes significant sympathetic response resulting in hypertension and tachycardia. In individuals with systemic hypertension, coronary artery disease, cerebrovascular disease and intracranial aneurysm, the effect of this transient sympathetic response can evoke life threatening conditions like pulmonary oedema, cardiac failure and cerebrovascular haemorrhage. METHODS: Patients were randomly divided into two groups, 30 in each group. Group I received 50 mg of esmolol and group II received lignocaine 2 mg/kg. Haemodynamic parameters like pulse, systolic blood pressure, diastolic blood pressure and mean arterial pressure were measured before induction of anaesthesia, immediately after intubation then at intervals of one minute, three minutes, five minutes, seven minutes and 10 minutes. RESULTS: There was no significant difference in demographic or base line vital signs between two groups (Table 1). The mean systolic blood pressure (SBP) increased on laryngoscopy and tracheal intubation by 15 mmHg in the group I whereas in group II it was 17.4 mmHg. There was a significant rise in diastolic blood pressure (DBP) in both the groups, but the rise was lesser in group II than in group I. CONCLUSION: Both esmolol and lignocaine were not effective in attenuating hemodynamic stress response to laryngoscopy and tracheal intubation; however esmolol was superior to lignocaine in blunting the stress response. PMID- 26905704 TI - Symptoms Analysis of Obsessive-Compulsive Disorder in Adolescents and Adults in a Teaching Hospital. AB - INTRODUCTION: Obsessive-compulsive disorder has a broadly diverse clinical expression that reflects heterogeneity. Several studies have identified consistent symptom dimensions of obsessive-compulsive disorder. The purpose of this study was to conduct an exploratory symptoms analysis of obsessive compulsive symptoms in adolescents and adults with obsessive-compulsive disorder. METHODS: This was a cross-sectional study conducted in the Department of Psychiatry, National Medical College. This study examined lifetime occurrence of obsessive-compulsive symptoms included in the 13 symptom categories of the Yale Brown Obsessive Compulsive Scale. Symptoms analysis was performed on 60 patients with obsessive-compulsive disorder. Eight categories of obsessions and six categories of compulsions from Yale-Brown Obsessive Compulsive Scale were included in the analyses. SPSS software package (version 16) was used to analyze the data and shown in the table. RESULTS: Of 60 adolescents and adults, female and male were in the ratio of 1.2:1. Contamination was the most common occurring obsession followed by aggressive obsession. The most common occurring compulsion was checking followed by washing. Only a minority of patients (13.33%) presented predominantly with obsessions however 18.33% patients presented predominantly with compulsions. Certain obsessions and compulsions co-occur to form a cluster. CONCLUSIONS: In adolescents and adults, obsessive-compulsive disorder is a multidimensional disorder. Symptom dimensions are predominantly congruent with those described in similar studies of adults with obsessive-compulsive disorder. PMID- 26905705 TI - Induction of Labor Using Misoprostol With or Without Mifepristone in Intrauterine Death. AB - INTRODUCTION: Rapid expulsion of fetus in intrauterine fetal death is usually requested without any medical grounds for it. So an efficient, safe method for induction of labor is required. The objective of this study is to determine if pre-treatment with mifepristone followed by induction of labor with misoprostol in late intrauterine fetal death is more efficacious. METHODS: We conducted a randomized controlled trial in 100 patients in B.P.Koirala Institute of Health Sciences, Nepal from June 2011 to May 2013. Group A women received single oral dose of 200 mg mifepristone, followed by induction with vaginal misoprostol after 24 hours. Group B women were induced only with vaginal misoprostol. In each group, five doses of misoprostol was used four hourly. If first cycle was unsuccessful, after break of 12 hour, second course of misoprostol was started. The primary outcome was a measure of induction to delivery time and vaginal delivery within 24 hours. Secondary outcome was to measure need of oxytocin and complications. RESULTS: Maternal age, parity and period of gestation were comparable between groups. Number of misoprostol dose needed in group A was significantly less than group B. Mann Whitney U test showed, women in group A had significantly earlier onset of labor, however total induction to delivery interval was not significant. In group A, 85.7% delivered within 24 hours of first dose of misoprostol while in group B 70% delivered within 24 hours (p=0.07). More women in Group B required oxytocin. CONCLUSIONS: Pretreatment with mifepristone before induction of labor following late intrauterine fetal death is an effective and safe regimen. It appears to shorten the duration of induction to onset of labor. PMID- 26905706 TI - Overweight and Obesity among the Adolescent School Students in Belgaum City. AB - INTRODUCTION: The World Health Organization defines obesity as a 'global epidemic'. An overweight adolescent has a 70% chance of becoming obese. Overweight and obese adolescents are at higher risk for developing long-term chronic diseases. So the present study objective is to estimate the prevalence of overweight and obesity among adolescent school students METHODS: A sample size of 300 adolescent students was taken to do a cross-sectional study. Body weight and height were recorded and body mass index was categorized based on age-and sex specific cut-off values as per International Obesity Task Force reference growth charts. Proportions of obese, overweight and underweight children were calculated and subjected to chi-square and logistic regression tests at the p < 0.05 significance level. RESULTS: The overall prevalence of overweight and obesity in the present study were 12% and 3.3% respectively. The highest prevalence was among those aged 15 years i.e. 36.7%. The prevalence of overweight and obesity was higher among the subject who did not practice physical activity and whose family income was more than 10,000 per month. CONCLUSIONS: Prevalence of overweight and obesity among adolescents student in Belgaum city was high which is statistically associated with less physically activity and monthly income of parent. PMID- 26905707 TI - Large versus Small Dose Magnesium Sulfate Infusion in Tetanus. AB - INTRODUCTION: Evidence based guidelines regarding the use of magnesium sulfate in tetanus is lacking. Hence, our objective was to compare two infusion doses of magnesium sulfate to control the tetanic spasms. METHODS: Data of 14 adult male patients admitted in the intensive care unit were retrieved. Twelve adult ventilated patients received magnesium infusion as an adjunct to diazepam therapy to control tetanic spasms. We retrospectively divided them into two groups for comparison. Group 1 patients (n=7) received a smaller dose (<1 g.h(-1)) than group 2 (n=5) (1.5 to 2 g.h(-1)). RESULTS: The duration of symptoms before arrival to hospital was significantly longer in group 1 than group 2. The Ablett severity grade was II in three patients in group 1 and III in all patients of group 2. In Ablett severity grade III patients, the diazepam dose used was significantly higher in group 1 (n=4) (292+/-48 mg.d(-1)) than group 2 (n=3) (106+/-9 mg.d(-1)) as magnesium infusion dose was restricted due to hypotension in group 1. Amongst the patients who received MgSO(4) for >=10 days, the requirement of diazepam was significantly reduced in the second week (174.1+/ 59.2 mg/d) than the first week (325.4+/-105.9 mg.d(-1)) of infusion in group 2 (n=4) but not in group 1 patients (n=4). CONCLUSIONS: The larger dose of MgSO(4) infusion was titrated to control tetanic spasms as an adjunct to diazepam in select group of patients without hypotension. Uncontrolled hypotension, cardiac arrhythmia and renal failure were the factors to limit its infusion dose. PMID- 26905708 TI - Smoking and Thromboangitis Obliterans- Are they related ? AB - INTRODUCTION: In 1908 Leo Buerger first gave the world the clinical picture of this dreadful disease which he called Thromboangitis Obliterans. Virtually all investigators believe that smoking or tobacco use in some form is a requirement for the diagnosis of Thromboangitis Obliterans. We studied the demographic profile and smoking pattern of patients with Thromboangiitis Obliterans. METHODS: Retrospective study carried out in a tertiary level hospital of South India from 1st January 1997 to 31st December 2003. Patients fulfilling Shionoya's criteria form the study group. Incidence of Thromboangitis Obliterans, relation to smoking habits, type and nature of manifestation were analyzed. RESULTS: A total of 105 cases were studied and found to have declining pattern of incidence from 0.9% 0.3%. All patients were males, smokers at the time admission and 76% out of them were from low socioeconomic background. Patients smoking 5-15 cigarettes per day, for 5-10 years duration constituted 45% of the study group. The most frequent reasons for being referred to hospital were ischemic ulcers (83.80%), claudication (78.0%) and rest pain (26.66%). CONCLUSIONS: In those who present early with the disease the number of cigarettes and duration of smoking shows no direct correlation to the severity. Most patients continue to smoke inspite of counseling and awareness that the disease progresses due to smoking. Ulcer, intermittent claudication and rest pain are the three common presenting symptoms of Thromboangitis Obliterans. PMID- 26905709 TI - Close Versus Limited Open Method of Ender's Nail Fixation in Paediatric Femoral Shaft Fractures. AB - INTRODUCTION: There are various surgical options for treating fracture of femoral shaft in children. Here we compare the results of close with limited open method of Ender's nails fixation of femoral shaft fractures in children. METHODS: We studied 60 children with femoral shaft fractures in age group 5-15 years. Ender's nail fixation was done by close technique in 40 cases and in 20 cases by limited open technique. RESULTS: The mean operative time was significantly high in limited open group being 64 minutes in comparison to 50 minutes in close group. There was no significant difference between close and limited open groups with respect to time for partial weight bearing and time for full weight bearing. Fracture united sooner in close group as compared to open group. Union was achieved in all patients within a mean of 11 weeks in close group in comparison to 12.4 weeks in open group. According to the Flynn criteria in close group 34 patients had excellent results, 6 had satisfactory and none poor. In limited open group outcome was excellent in 14 patients, satisfactory in 4 patients and 2 had poor result. There was no significant difference in outcome based on Flynn criteria between two groups. CONCLUSIONS: Though operative time is more and healing is delayed in Ender's nail fixation by limited open technique, there is no statistical difference in final outcome as per Flynn criteria between close and limited open technique of Ender's nail fixation of femoral shaft fractures in children. PMID- 26905710 TI - Analysis of Health Sector Budget of Nepal. AB - INTRODUCTION: Primarily, health sector connects two segments - medicine and public health, where medicine deals with individual patients and public health with the population health. Budget enables both the disciplines to function effectively. The Interim Constitution of Nepal, 2007 has adapted the inspiration of federalism and declared the provision of basic health care services free of cost as a fundamental right, which needs strengthening under foreseen federalism. METHODS: An observational retrospective cohort study, aiming at examining the health sector budget allocation and outcome, was done. Authors gathered health budget figures (2001 to 2013) and facts published from authentic sources. Googling was done for further information. The keywords for search used were: fiscal federalism, health care, public health, health budget, health financing, external development partner, bilateral and multilateral partners and healthcare accessibility. The search was limited to English and Nepali-language report, articles and news published. RESULTS: Budget required to meet the population's need is still limited in Nepal. The health sector budget could not achieve even gainful results due to mismatch in policy and policy implementation despite of political commitment. CONCLUSIONS: Since Nepal is transforming towards federalism, an increased complexity under federated system is foreseeable, particularly in the face of changed political scenario and its players. It should have clear goals, financing policy and strict implementation plans for budget execution, task performance and achieving results as per planning. Additionally, collection of revenue, risk pooling and purchasing of services should be better integrated between central government and federated states to horn effectiveness and efficiency. PMID- 26905711 TI - Charcot's Elbow Following Syringomyelia: Revisited. AB - Neuropathic arthropathy of the elbow joint is uncommon with a reported incidence of 3-8%only. The natural history, pathogenesis and management approaches are debatable with an absence of clear guidelines. We report two cases of Charcot's elbow following syringomyelia with ulnar nerve manifestations. One patient required debulkingsynovectomy and ulnar nerve decompression while the other was managed conservatively. The article aims to enrich the limited knowledge of managing Charcot's elbow. PMID- 26905712 TI - Fetal Craniotomy. AB - Nowadays, even in developing countries Cesarean section is the most common method of delivery for the breech presentation. However, in rural parts of the countries still vaginal route is the only option. Trauma to the after coming head is the common issue among the contributors of birth trauma during breech delivery. Entrapment of after coming head is an unpredictable obstetrical emergency. If the fetus is alive, options from application of obstetric forceps to giving Duhrssen incisions can be kept in choice. Cesarean section is done when all the methods fail to deliver the head. But, when the fetus is not salvageable, delivery of after coming head by craniotomy can reduce unnecessary morbidity of Cesarean section. In the present report, a case with entrapment of after coming head of dead preterm fetus for 6 hrs of home delivery was described and the management of this condition was reviewed. PMID- 26905713 TI - Bilateral Synchronous Testicular Seminoma in a Patient with Bilateral Cryptorchidism. AB - Cryptorchidism is a known cause of testicular tumor. The incidence of testicular tumor is 11 times more in inguinal testes and 50 times more in intra-abdominal testes. The position of the undescended testis is related to the likelihood of carcinogenesis with the intra-abdominal location having the highest risk for malignancy. Bilateral testicular tumors are rare and 80% of bilateral tumors are metachronous. Synchronous bilateral testicular tumors are rare and bilateral synchronous testicular seminoma in a patient with bilateral cryptorchidism is very rare. PMID- 26905714 TI - Hashimoto's Thyroiditis and Medullary Carcinoma of Thyroid. AB - Hashimoto's thyroiditis (HT) has been found to be associated with lymphoma, papillary carcinoma and Hurthle cell neoplasms of thyroid. In contrast, there are only a few reports of co-existence of HT with medullary carcinoma of thyroid. An overall prevalence of medullary carcinoma of only 0.35% has been reported in HT patients. Such a rare combination is being presented here. A 33 year old female presented with history of goiter for one year. Fine needle aspiration cytology (FNAC) of the swelling revealed cytological features suggestive of medullary carcinoma of thyroid. Histopathological examination of total thyroidectomy specimen revealed Hashimoto's thyroiditis along with medullary carcinoma of thyroid. Although Hashimoto's thyroiditis can uncommonly co-exist with thyroid neoplasm, its association with medullary carcinoma is extremely rare and hence being presented. PMID- 26905715 TI - Fontan Failure and Thrombosis of Total Cavo-Pulmonary Connection Conduit. AB - The immediate postoperative period of Fontan operation is frequently complicated by hemodynamic instability, sometimes requiring fenestration of the conduit. Thrombosis of total cavo-pulmonary connection conduit warrants early intervention to prevent systemic and pulmonary embolism. We report a case of Fontan failure requiring fenestration; which was further complicated by thrombosis of total cavo pulmonary connection conduit and managed with anticoagulants. PMID- 26905716 TI - Dermoid Cyst and its bizarre presentation. AB - Dermoid cysts or mature cystic teratoma are the most common type of ovarian germ cell tumor usually occurring in the reproductive age group. They are commonly unilateral and 10-12 % can be bilateral. They are commonly multicystic and contain sebaceous fluid as well as tissue of three germ cell layers e.g. ectoderm (skin, hair, brain) mesoderm (muscle, fat ,teeth ,bone, and cartilage) and endoderm (mucious and ciliated epithelium).These teratomas usually arise from the gonads but has been found anywhere in the body. Their site, size and clinical presentations are extremely variable causing confusion with medical and surgical diseases, acute emergency due to rupture and torsion , bowel and bladder injuries, and pregnancy etc. The malignant teratoma occurs at 3-4% only among ovarian carcinoma. The malignant transformation in benign cysts is a rare occurrence with 1-2% cases and squamous cell carcinoma being the commonest. This review is undertaken to study the different presentations produced by these tumors. PMID- 26905717 TI - Developing an Index to Measure Health System Performance: Measurement for Districts of Nepal. AB - Various frameworks for measuring health system performance have been proposed and discussed. The scope of using performance indicators are broad, ranging from examining national health system to individual patients at various levels of health system. Development of innovative and easy index is essential to measure multidimensionality of health systems. We used indicators, which also serve as proxy to the set of activities, whose primary goal is to maintain and improve health. We used eleven indicators of MDGs, which represent all dimensions of health to develop index. These indicators are computed with similar methodology that of human development index. We used published data of Nepal for computation of the index for districts of Nepal as an illustration. To validate our finding, we compared the indices of these districts with other development indices of Nepal. An index for each district has been computed from eleven indicators. Then indices are compared with that of human development index, socio-economic and infrastructure development indices and findings has shown the similarity on distribution of districts. Categories of low and high performing districts on health system performance are also having low and high human development, socio economic, and infrastructure indices respectively. This methodology of computing index from various indicators could assist policy makers and program managers to prioritize activities based on their performance. Validation of the findings with that of other development indicators show that this can be one of the tools, which can assist on assessing health system performance for policy makers, program managers and others. PMID- 26905718 TI - Strengthening Free Healthcare in Rural Nepal. AB - Nepal, a mountainous country in South East Asia, still lags in increasing access to healthcare and reducing health inequity. Possible Non Government Organization based in Achham, Nepal, which is a sister organization of Possible International Non Government Organization based in New York, USA recognized the increasing health needs in the far western rural hilly parts of Nepal, where extreme poverty and illiteracy was creating a vulnerable picture especially in Achham. Possible (previously named Nyaya Health) started to operate Bayalpata Hospital in 2009 after completing more than one year of free health services in Sanfe-Bagar, Achham, in partnership with the Nepalese Ministry of Health and Population. It supports the idea that free health service has its own challenges but a public private partnership can thrive while promote equity in health services. PMID- 26905719 TI - Automated Gravimetric Calibration to Optimize the Accuracy and Precision of TECAN Freedom EVO Liquid Handler. AB - High-throughput screening technologies are increasingly integrated into the formulation development process of biopharmaceuticals. The performance of liquid handling systems is dependent on the ability to deliver accurate and precise volumes of specific reagents to ensure process quality. We have developed an automated gravimetric calibration procedure to adjust the accuracy and evaluate the precision of the TECAN Freedom EVO liquid handling system. Volumes from 3 to 900 uL using calibrated syringes and fixed tips were evaluated with various solutions, including aluminum hydroxide and phosphate adjuvants, beta-casein, sucrose, sodium chloride, and phosphate-buffered saline. The methodology to set up liquid class pipetting parameters for each solution was to split the process in three steps: (1) screening of predefined liquid class, including different pipetting parameters; (2) adjustment of accuracy parameters based on a calibration curve; and (3) confirmation of the adjustment. The run of appropriate pipetting scripts, data acquisition, and reports until the creation of a new liquid class in EVOware was fully automated. The calibration and confirmation of the robotic system was simple, efficient, and precise and could accelerate data acquisition for a wide range of biopharmaceutical applications. PMID- 26905720 TI - Variation in Residential Care Community Nurse and Aide Staffing Levels: United States, 2014. AB - OBJECTIVES: This report presents national and state estimates of staffing levels in residential care communities for registered nurses, licensed practical or vocational nurses, and aides in the United States for 2014. METHODS: Data were drawn from the residential care community component of the 2014 wave of the biennial National Study of Long-Term Care Providers, conducted by the Centers for Disease Control and Prevention's National Center for Health Statistics. For each staff type, the "staffing level" measure is presented as average hours per resident per day, defined as the total number of hours worked divided by the total number of residents, which does not necessarily reflect the amount of care given to a specific resident. Analyses examined the extent to which residential care community nurse and aide staffing levels varied by selected organizational characteristics and selected resident composition characteristics of the communities. Differences among subgroups were evaluated using two-sided t tests at the 0.05 level. RESULTS: In 2014, the total registered nurse, licensed practical or vocational nurse, and aide staffing level among all residential care communities was about 2 hours and 50 minutes. Registered nurse staffing levels differed for two of the three organizational characteristics (size and metropolitan statistical area [MSA]) and for only one of the four resident composition characteristics (primarily serving residents needing any assistance with activities of daily living). Licensed practical or vocational nurse staffing levels differed for all three organizational characteristics (size, MSA, and ownership) and for only one of the four resident composition characteristics (primarily serving residents diagnosed with Alzheimer's disease or other dementias). In contrast, differences in aide staffing levels were common when examining both community organizational and resident composition characteristics. Registered nursing, licensed practical and vocational nursing, and aide staffing levels varied geographically by state. PMID- 26905721 TI - Selective Adsorption of n-Alkanes from n-Octane on Metal-Organic Frameworks: Length Selectivity. AB - The liquid-phase adsorption of n-alkanes (from n-octane (C8) solvent) with different chain lengths was carried out over three metal-organic frameworks (MOFs), viz., metal-azolate framework-6 (MAF-6), copper-benzenetricarboxylate (Cu BTC), and iron-benzenetricarboxylate (MIL-100(Fe)), and a conventional adsorbent activated carbon (AC). MAF-6 and Cu-BTC were found to have significant selectivity for the adsorption of n-dodecane (C12) and n-heptane (C7), respectively, from C8. Selectivity for C12 on MAF-6 was also observed in competitive adsorption from binary adsorbate systems. To understand the selective adsorption of C12 on MAF-6 more, the adsorption of C12 from C8 over MAF-6 was investigated in detail and compared with that over AC. The obtained selectivities over MAF-6 and Cu-BTC for C12 and C7, respectively, might be explained by the similarity between cavity size of adsorbents and molecular length of n-alkanes. In the case of AC and MIL-100(Fe), no specific adsorption selectivity was observed because the cavity sizes of the two adsorbents are larger than the size of the n-alkanes used in this study. The adsorption capacities (qt) of n-alkanes over AC and MIL-100(Fe) decreased and increased, respectively, as the polarity (or length) of the adsorbates increased, probably because of nonpolar and polar interactions between the adsorbents and n-alkanes. On the basis of the results obtained, it can be concluded that matching the cavity size (of adsorbents) with the molecular length (of n-alknaes) is more important parameter than the MOF's hydrophilicity/hydrophobicity for the selective adsorption/separation of alkanes. PMID- 26905722 TI - Posterolateral ankle ligament injuries affect ankle stability: a finite element study. AB - BACKGROUND: We have already discovered 23 patients during the work of the outpatient department and operations whose unstable signs on the posterolateral ankle. The anterior drawer test demonstrated normal during the physical examinations while the spaces of the posterior tibiotalar joints increased in stress X-ray plain films. ATFL intact and posterolateral ligaments lax were found during operations too. It is important to make existence claims and illuminate the mechanism of posterolateral ankle instability. METHODS: A finite element model of the ankle was established for simulating to cut off posterolateral ligaments in turn. Ankle movements with tibia rotation under load on five forefoot positions were simulated as well. RESULTS: The difference values with tibia external rotation were negative, and the positive results occurred with tibia internal rotation. The tibia-talus difference values in some forefoot positions were 2 ~ 3 mm after PTFL together with CFL or/and PITFL were cut off. The tibula-talus difference values were 2.21 ~ 2.76 mm after both PTFL and CFL were cut off. The tibia-fibula difference values were small. The difference values increased by 2 ~ 5 mm after cutting off the PITFL. CONCLUSIONS: Posterolateral ankle ligaments, especially CFL and PITFL, play a significant role in maintaining ankle stability. The serious injuries of both CFL and PITFL would affect posterolateral ankle stabilities. PITFL was important to subtalar joint stability. PMID- 26905723 TI - Immunogenicity of parenterally delivered plant-derived small and medium surface antigens of hepatitis B virus. AB - KEY MESSAGE: Intramuscularly delivered plant-derived M-HBsAg was compared to S HBsAg, and as a result elicited specific anti-preS2 antibodies and significantly higher titre of anti-HBs antibodies, together with IgG isotype profile indicating some Th1 polarisation, apart from the main Th2 response. HBV prevalence is still threatening, regardless of prevention programmes using vaccines containing S HBsAg, supplemented by third-generation vaccines, comprising also M- and L-HBsAg. Plant expression systems offer a cost-effective production option of the antigens. Plant-derived S- and M-HBsAg, intramuscularly delivered to mice, elicited anti-HBs antibodies several times higher than high responsiveness threshold titre. M-HBsAg induced stronger response of anti-HBs and also specific anti-preS2 antibodies. IgG isotype profiles indicated mainly Th2 response, yet Th1 polarisation was also pointed out, in some larger extent for M-HBsAg. These results correspond to research on CHO-derived M-HBsAg vs. commercial vaccines based on S-HBsAg and support potency of plant-derived antigens as alternative injection vaccines. PMID- 26905725 TI - Spermine modulates the expression of two probable polyamine transporter genes and determines growth responses to cadaverine in Arabidopsis. AB - KEY MESSAGE: Two genes, LAT1 and OCT1 , are likely to be involved in polyamine transport in Arabidopsis. Endogenous spermine levels modulate their expression and determine the sensitivity to cadaverine. Arabidopsis spermine (Spm) synthase (SPMS) gene-deficient mutant was previously shown to be rather resistant to the diamine cadaverine (Cad). Furthermore, a mutant deficient in polyamine oxidase 4 gene, accumulating about twofold more of Spm than wild type plants, showed increased sensitivity to Cad. It suggests that endogenous Spm content determines growth responses to Cad in Arabidopsis thaliana. Here, we showed that Arabidopsis seedlings pretreated with Spm absorbs more Cad and has shorter root growth, and that the transgenic Arabidopsis plants overexpressing the SPMS gene are hypersensitive to Cad, further supporting the above idea. The transgenic Arabidopsis overexpressing L-Amino acid Transporter 1 (LAT1) absorbed more Cad and showed increased Cad sensitivity, suggesting that LAT1 functions as a Cad importer. Recently, other research group reported that Organic Cation Transporter 1 (OCT1) is a causal gene which determines the Cad sensitivity of various Arabidopsis accessions. Furthermore, their results suggested that OCT1 is involved in Cad efflux. Thus we monitored the expression of OCT1 and LAT1 during the above experiments. Based on the results, we proposed a model in which the level of Spm content modulates the expression of OCT1 and LAT1, and determines Cad sensitivity of Arabidopsis. PMID- 26905724 TI - Cytoplasmic male sterility (CMS) in hybrid breeding in field crops. AB - KEY MESSAGE: A comprehensive understanding of CMS/Rf system enabled by modern omics tools and technologies considerably improves our ability to harness hybrid technology for enhancing the productivity of field crops. Harnessing hybrid vigor or heterosis is a promising approach to tackle the current challenge of sustaining enhanced yield gains of field crops. In the context, cytoplasmic male sterility (CMS) owing to its heritable nature to manifest non-functional male gametophyte remains a cost-effective system to promote efficient hybrid seed production. The phenomenon of CMS stems from a complex interplay between maternally-inherited (mitochondrion) and bi-parental (nucleus) genomic elements. In recent years, attempts aimed to comprehend the sterility-inducing factors (orfs) and corresponding fertility determinants (Rf) in plants have greatly increased our access to candidate genomic segments and the cloned genes. To this end, novel insights obtained by applying state-of-the-art omics platforms have substantially enriched our understanding of cytoplasmic-nuclear communication. Concomitantly, molecular tools including DNA markers have been implicated in crop hybrid breeding in order to greatly expedite the progress. Here, we review the status of diverse sterility-inducing cytoplasms and associated Rf factors reported across different field crops along with exploring opportunities for integrating modern omics tools with CMS-based hybrid breeding. PMID- 26905726 TI - Identification of the ASR gene family from Brachypodium distachyon and functional characterization of BdASR1 in response to drought stress. AB - KEY MESSAGE: A genome-wide investigation identified five B. distachyon ASR genes. BdASR1 may be a transcription factor that confers drought resistance by activating antioxidant systems involving ROS-scavenging enzymes and non-enzymatic antioxidants. Abscisic acid-, stress-, and ripening-induced (ASR) proteins belong to a family of plant-specific, small, and hydrophilic proteins with important roles in responses to abiotic stresses. Although several ASR genes involved in drought tolerance have been characterized in various plant species, the mechanisms regulating ASR activities are still uncharacterized. Additionally, no research on Brachypodium distachyon ASR proteins have been completed. In this study, five B. distachyon BdASR genes were identified through genome-wide analyses. Phylogenetic analyses revealed that BdASR genes originated from tandem and whole genome duplications. Expression analyses revealed the BdASR genes responded to various abiotic stresses, including cold, drought, and salinity, as well as signaling molecules such as abscisic acid, ethylene, and H2O2. BdASR1, which localizes to the nucleus and is transcriptionally active, was functionally characterized. BdASR1 overexpression considerably enhanced drought tolerance in transgenic tobacco plants, which was accompanied by increased superoxide dismutase, catalase, and peroxidase activities, as well as an increased abundance of antioxidants such as ascorbate, tocopherols, and glutathione. BdASR1 may function as a transcription factor that provides drought stress resistance by inducing the production of reactive oxygen species-scavenging enzymes and non enzymatic antioxidants. PMID- 26905728 TI - Expert-Guided Generative Topographical Modeling with Visual to Parametric Interaction. AB - Introduced by Bishop et al. in 1996, Generative Topographic Mapping (GTM) is a powerful nonlinear latent variable modeling approach for visualizing high dimensional data. It has shown useful when typical linear methods fail. However, GTM still suffers from drawbacks. Its complex parameterization of data make GTM hard to fit and sensitive to slight changes in the model. For this reason, we extend GTM to a visual analytics framework so that users may guide the parameterization and assess the data from multiple GTM perspectives. Specifically, we develop the theory and methods for Visual to Parametric Interaction (V2PI) with data using GTM visualizations. The result is a dynamic version of GTM that fosters data exploration. We refer to the new version as V2PI GTM. In this paper, we develop V2PI-GTM in stages and demonstrate its benefits within the context of a text mining case study. PMID- 26905727 TI - Cell wall-related genes studies on peach cultivars with differential susceptibility to woolliness: looking for candidates as indicators of chilling tolerance. AB - KEY MESSAGE: The results obtained indicate that a beta-xylosidase gene may act as good indicator of chilling tolerance and provide new insights into the complex issue of peach fruit woolliness. The storage of peaches at low temperatures for prolonged periods can induce a form of chilling injury (CI) called woolliness, characterized by a lack of juiciness and a mealy texture. As this disorder has been associated with abnormal cell wall dismantling, the levels of 12 transcripts encoding proteins involved in cell wall metabolism were analysed in cultivars with contrasting susceptibility to this disorder selected from five melting flesh peach cultivars. The resistant ('Springlady') and susceptible ('Flordaking') cultivars displayed differences in the level of expression of some of the selected genes during fruit softening and in woolly versus non-woolly fruits. From these genes, the level of expression of PpXyl, which encodes for a putative beta-xylosidase, was the one that presented the highest correlation (negative) with the susceptibility to woolliness. PpXyl expression was also analysed in a cultivar ('Rojo 2') with intermediate susceptibility to woolliness, reinforcing the conclusion about the correlation of PpXyl expression to the presence of woolliness symptom. Moreover, the level of expression of PpXyl correlated to protein level detected by Western blot. Analyses of the promoter region of the PpXyl gene (1637 bp) isolated from the three cultivars showed no differences suggesting that cis-elements from other regions of the genome and/or trans elements could be responsible of the differential PpXyl expression patterns. Overall, the results obtained indicate that PpXyl may act as a good indicator of woolliness tolerance and that the regulation of expression of this gene in different cultivars does not depend on sequences upstream the coding sequence. PMID- 26905730 TI - Using synoptic weather types to predict visitor attendance at Atlanta and Indianapolis zoological parks. AB - Defining an ideal "tourism climate" has been an often-visited research topic where explanations have evolved from global- to location-specific indices tailored to tourists' recreational behavior. Unfortunately, as indices become increasingly specific, they are less translatable across geographies because they may only apply to specific activities, locales, climates, or populations. A key need in the future development of weather and climate indices for tourism has been a translatable, meteorologically based index capturing the generalized ambient atmospheric conditions yet considering local climatology. To address this need, this paper tests the applicability of the spatial synoptic classification (SSC) as a tool to predict visitor attendance response in the tourism, recreation, and leisure (TRL) sector across different climate regimes. Daily attendance data is paired with the prevailing synoptic weather condition at Atlanta and Indianapolis zoological parks from September 2001 to June 2011, to review potential impacts ambient atmospheric conditions may have on visitor attendances. Results indicate that "dry moderate" conditions are most associated with high levels of attendance and "moist polar" synoptic conditions are most associated with low levels of attendance at both zoological parks. Comparing visitor response at these zoo locations, visitors in Indianapolis showed lower levels of tolerance to synoptic conditions which were not "ideal." Visitors in Indianapolis also displayed more aversion to "polar" synoptic regimes while visitors in Atlanta displayed more tolerance to "moist tropical" synoptic regimes. Using a comprehensive atmospheric measure such as the SSC may be a key to broadening application when assessing tourism climates across diverse geographies. PMID- 26905731 TI - Signaling Pathways Involved in Mammalian Sex Determination and Gonad Development. AB - The development of any organ system requires a complex interplay of cellular signals to initiate the differentiation and development of the heterogeneous cell and tissue types required to carry out the organs' functions. In this way, an extracellular stimulus is transmitted to an intracellular target through an array of interacting protein intermediaries, ultimately enabling the target cell to elicit a response. Surprisingly, only a small number of signaling pathways are implicated throughout embryogenesis and are used over and over again. Gonadogenesis is a unique process in that 2 morphologically distinct organs, the testes and ovaries, arise from a common precursor, the bipotential genital ridge. Accordingly, most of the signaling pathways observed throughout embryogenesis also have been shown to be important for mammalian sex determination and gonad development. Here, we review the mechanisms of signal transduction within these pathways and the importance of these pathways throughout mammalian gonad development, mainly concentrating on data obtained in mouse but including other species where appropriate. PMID- 26905729 TI - Isolation and identification of Candida species in patients with orogastric cancer: susceptibility to antifungal drugs, attributes of virulence in vitro and immune response phenotype. AB - BACKGROUND: Because of the inherent immunosuppression of cancer patients opportunistic infections by Candida spp, occur frequently. This study aimed to identify Candida species in the oral mucosa of 59 patients with orogastric cancer (OGC) and to analyze the immunological phenotype of these patients. METHODS: The yeasts were identified by MALDI-TOF mass spectrometry (MS). For all isolates, we performed phospholipases and proteinases assays, in vitro adherence to buccal epithelial cells (BEC), minimum inhibitory concentration of antifungal drugs and determined the cytokine profile by Cytometric Bead Array flow citometry assay. RESULTS: C. albicans was the most prevalent species in OGC patients (51.6 %) and control group (66.7 %). Candida spp. strains isolated from OGC patients exhibited better adherence to BEC (p = 0.05) than did the control group. Phospholipases production by Candida strains from OGC patients was lower (51.6 %) than in the control group (61.9 %). Proteinases were detected in 41.9 % and 4.8 % of the yeasts from OGC patients and control group, respectively. Significant differences were found in the serum of OGC patients compared to the control group for IL-2, IL-10, TNF-alpha, IFN-gamma and IL-17. CONCLUSIONS: The results of this work suggest increased virulence of yeasts isolated from OGC patients and, that this may interfere with the immune phenotype. PMID- 26905732 TI - Reliability and Criterion Validity of the Smartphone Inclinometer Application to Quantify Cervical Spine Mobility. AB - STUDY DESIGN: In this observational study, we compare fluid inclinometer and smartphone measures to analyze active cervical range of motion (ACROM) in healthy individuals. OBJECTIVE: The purpose of this study was to investigate the reliability and the criterion validity of a smartphone application to analyze head movements. SUMMARY OF BACKGROUND DATA: Recent studies on the reliability and the validity of customized smartphone applications to measure ACROM show good results for frontal and lateral planes' movement analysis, but poor results for the transverse plane. This can be due to the surrounding magnetic fields that affect the compass application used during head rotation valuation. METHODS: Twenty-three individuals were asked to perform neck maximal (end-range) movements (frontal flex-extension and left-right side flexion in the sitting position, left right rotation in the prone position). Two separate examiners took all ACROM measures and were assigned to each device (iPhone 5c and the inclinometer) contemporary for each individual. RESULTS: All measurements were taken twice to assess the intraobserver reliability. Interobserver and intraobserver reliabilities were evaluated using the intraclass correlation coefficient (ICC). The criterion validity between the 2 instruments was also assessed in terms of the ICC. The procedures used in this investigation for measuring ACROM yielded good validity (Pearson r>=0.99 and ICC>=0.99) between the 2 instruments for all movements. The Bland and Altman's 95% LoA ranged from -1.8 to 1.15 degrees. Percentage error values ranged from 1% to 3%. The intrarater and the interrater reliabilities were good (ICC>=0.9) for both instruments in all movements including the rotation movements (ICC>0.95). The minimal detectable change (MDC95) ranged from 4 to 8 degrees. CONCLUSIONS: This study confirms that the tested smartphone is valid and reliable to measure ACROM on the frontal and the sagittal planes; furthermore, it also demonstrates its usefulness for rotation movement analysis, using the inclinometric application. PMID- 26905734 TI - Ultrasound imaging of the human medial gastrocnemius muscle: how to orient the transducer so that muscle fascicles lie in the image plane. AB - The length and pennation of muscle fascicles are frequently measured using ultrasonography. Conventional ultrasonography imaging methods only provide two dimensional images of muscles, but muscles have complex three-dimensional arrangements. The most accurate measurements will be obtained when the ultrasound transducer is oriented so that endpoints of a fascicle lie on the ultrasound image plane and the image plane is oriented perpendicular to the aponeurosis, but little is known about how to find this optimal transducer orientation in the frequently-studied medial gastrocnemius muscle. In the current study, we determined the optimal transducer orientation at 9 sites in the medial gastrocnemius muscle of 8 human subjects by calculating the angle of misalignment between three-dimensional muscle fascicles, reconstructed from diffusion tensor images, and the plane of a virtual ultrasound image. The misalignment angle was calculated for a range of tilts and rotations of the ultrasound transducer relative to a reference orientation that was perpendicular to the skin and parallel to the tibia. With the transducer in the reference orientation, the misalignment was substantial (mean across sites and subjects of 6.5 degrees , range 1.4 to 20.2 degrees ). However for all sites and subjects a near-optimal alignment (on average 2.6 degrees , range 0.5 degrees to 6.0 degrees ) could be achieved by maintaining 0 degrees tilt and applying a small rotation (typically less than 10 degrees ). On the basis of these data we recommend that ultrasonographic measurements of medial gastrocnemius muscle fascicle architecture be obtained, at least for relaxed muscles under static conditions, with the transducer oriented perpendicular to the skin and nearly parallel to the tibia. PMID- 26905735 TI - Ghost-tree: creating hybrid-gene phylogenetic trees for diversity analyses. AB - BACKGROUND: Fungi play critical roles in many ecosystems, cause serious diseases in plants and animals, and pose significant threats to human health and structural integrity problems in built environments. While most fungal diversity remains unknown, the development of PCR primers for the internal transcribed spacer (ITS) combined with next-generation sequencing has substantially improved our ability to profile fungal microbial diversity. Although the high sequence variability in the ITS region facilitates more accurate species identification, it also makes multiple sequence alignment and phylogenetic analysis unreliable across evolutionarily distant fungi because the sequences are hard to align accurately. To address this issue, we created ghost-tree, a bioinformatics tool that integrates sequence data from two genetic markers into a single phylogenetic tree that can be used for diversity analyses. Our approach starts with a "foundation" phylogeny based on one genetic marker whose sequences can be aligned across organisms spanning divergent taxonomic groups (e.g., fungal families). Then, "extension" phylogenies are built for more closely related organisms (e.g., fungal species or strains) using a second more rapidly evolving genetic marker. These smaller phylogenies are then grafted onto the foundation tree by mapping taxonomic names such that each corresponding foundation-tree tip would branch into its new "extension tree" child. RESULTS: We applied ghost-tree to graft fungal extension phylogenies derived from ITS sequences onto a foundation phylogeny derived from fungal 18S sequences. Our analysis of simulated and real fungal ITS data sets found that phylogenetic distances between fungal communities computed using ghost-tree phylogenies explained significantly more variance than non-phylogenetic distances. The phylogenetic metrics also improved our ability to distinguish small differences (effect sizes) between microbial communities, though results were similar to non-phylogenetic methods for larger effect sizes. CONCLUSIONS: The Silva/UNITE-based ghost tree presented here can be easily integrated into existing fungal analysis pipelines to enhance the resolution of fungal community differences and improve understanding of these communities in built environments. The ghost-tree software package can also be used to develop phylogenetic trees for other marker gene sets that afford different taxonomic resolution, or for bridging genome trees with amplicon trees. AVAILABILITY: ghost tree is pip-installable. All source code, documentation, and test code are available under the BSD license at https://github.com/JTFouquier/ghost-tree . PMID- 26905733 TI - Regulation of epithelial-mesenchymal transition through epigenetic and post translational modifications. AB - The epithelial to mesenchymal transition (EMT) is a biological process in which a non-motile epithelial cell changes to a mesenchymal phenotype with invasive capacities. This phenomenon has been well documented in multiple biological processes including embryogenesis, fibrosis, tumor progression and metastasis. The hallmark of EMT is the loss of epithelial surface markers, most notably E cadherin, and the acquisition of mesenchymal markers including vimentin and N cadherin. The downregulation of E-cadherin during EMT can be mediated by its transcriptional repression through the binding of EMT transcription factors (EMT TFs) such as SNAIL, SLUG and TWIST to E-boxes present in the E-cadherin promoter. Additionally, EMT-TFs can also cooperate with several enzymes to repress the expression of E-cadherin and regulate EMT at the epigenetic and post- translational level. In this review, we will focus on epigenetic and post- translational modifications that are important in EMT. In addition, we will provide an overview of the various therapeutic approaches currently being investigated to undermine EMT and hence, the metastatic progression of cancer as well. PMID- 26905736 TI - Effect of Prebiotic Galacto-Oligosaccharides on Serum Lipid Profile of Hypercholesterolemics. AB - The present study focused on the role of galacto-oligosaccharides (GOS) against the development of hypercholesterolemia. In the current research, GOS synthesized from lactose solution were fed to hypercholesterolemic female Sprague-Dawley rats. Negative control group (G1) was fed on standard basal diet alone. Positive control group (G5) was fed on inulin (154 mg/250 g body weight), while treatment groups G2, G3 and G4 received 110 mg, 154 mg and 198.4 mg/250 g body weight, respectively, of GOS along with high-fat diet for a period of 60 days. Findings from this study revealed that animals belonging to prebiotic GOS (G2, G3 and G4) fed group showed significantly decreased serum triglycerides, total cholesterol, LDL cholesterol and VLDL cholesterol as compared to control group (G0). The groups which were fed on different doses of GOS revealed a significant reduction in TC, TG, LDL, and VLDL levels and an increase in HDL level corresponding to the reference group that was fed on inulin, while G1 negative control group revealed increased levels of TC, TG, LDL and VLDL. In contrast to positive control group G5 (154 mg inulin), all doses of GOS lowered serum TC, TG and LDL-C and raised HDL-C; however, G4 (198.4 mg) proved to be more effective. Hence, GOS proved to be supportive in preventing hypercholesterolemia leading cause of cardiovascular disease and atherosclerosis. This study reported a significant reduction of serum TC, TG and LDL-C in female rats for 60 days as compared to control. Conclusively, GOS were found to be worthless against hypercholesterolemia. PMID- 26905737 TI - Camphor-mediated synthesis of carbon nanoparticles, graphitic shell encapsulated carbon nanocubes and carbon dots for bioimaging. AB - A green method for an efficient synthesis of water-soluble carbon nanoparticles (CNPs), graphitic shell encapsulated carbon nanocubes (CNCs), Carbon dots (CDs) using Camphor (Cinnamomum camphora) is demonstrated. Here, we describe a competent molecular fusion and fission route for step-wise synthesis of CDs. Camphor on acidification and carbonization forms CNPs, which on alkaline hydrolysis form CNCs that are encapsulated by thick graphitic layers and on further reduction by sodium borohydride yielded CDs. Though excitation wavelength dependent photoluminescence is observed in all the three carbon nanostructures, CDs possess enhanced photoluminescent properties due to more defective carbonaceous structures. The surface hydroxyl and carboxyl functional groups make them water soluble in nature. They possess excellent photostability, higher quantum yield, increased absorption, decreased cytotoxicity and hence can be utilized as a proficient bio imaging agent. PMID- 26905738 TI - Cranberry Resistance to Dodder Parasitism: Induced Chemical Defenses and Behavior of a Parasitic Plant. AB - Parasitic plants are common in many ecosystems, where they can structure community interactions and cause major economic damage. For example, parasitic dodder (Cuscuta spp.) can cause up to 80-100 % yield loss in heavily infested cranberry (Vaccinium macrocarpon) patches. Despite their ecological and economic importance, remarkably little is known about how parasitic plants affect, or are affected by, host chemistry. To examine chemically-mediated interactions between dodder and its cranberry host, we conducted a greenhouse experiment asking whether: (1) dodder performance varies with cranberry cultivar; (2) cultivars differ in levels of phytohormones, volatiles, or phenolics, and whether such variation correlates with dodder parasitism; (3) dodder parasitism induced changes in phytohormones, volatiles, or phenolics, and whether the level of inducible response varied among cultivars. We used five cranberry cultivars to assess host attractiveness to dodder and dodder performance. Dodder performance did not differ across cultivars, but there were marginally significant differences in host attractiveness to dodder, with fewer dodder attaching to Early Black than to any other cultivar. Dodder parasitism induced higher levels of salicylic acid (SA) across cultivars. Cultivars differed in overall levels of flavonols and volatile profiles, but not phenolic acids or proanthocyanidins, and dodder attachment induced changes in several flavonols and volatiles. While cultivars differed slightly in resistance to dodder attachment, we did not find evidence of chemical defenses that mediate these interactions. However, induction of several defenses indicates that parasitism alters traits that could influence subsequent interactions with other species, thus shaping community dynamics. PMID- 26905740 TI - Blastocystis subtypes in cancer patients: Analysis of possible risk factors and clinical characteristics. AB - The aim of the present study was to examine the frequency and genetic diversity of Blastocystis in cancer patients of a Medical Oncology Department in Aydin, Turkey. Patients' stool samples were examined between January 2013 and February 2014 by both microscopy and culture methods. Culture positive samples were subjected to DNA isolation and Sequence Tagged Site (STS)-PCR analysis. Possible etiological factors and clinical features of Blastocystis infection were also analyzed and compared between Blastocystis infected and non-infected subgroups. Blastocystis was detected in 15 (6.5%) of 232 stool samples by microscopy and in 25 (10.8%) by culture methods. Out of 25 culture positive isolates, the most prevalent subtype was ST3 (59%), followed by ST1 (23%) and ST2 (18%). Blastocystis frequency was higher in the male patients than the females (19% vs. 6.5%, p<0.05) and in the patients living in urban areas than rural (15.3% vs. 6.6%, p<0.05). Interestingly, Blastocystis was more frequent in patients with lung cancer than the other cancer types (chi2=18, p<0.05) and also in the patients who had received at least eight chemotherapy cycles than fewer (21.4% vs. 9.9%, p<0.05). The rate of gastrointestinal symptoms was not significantly different between infected and non-infected cases. The pathogenic and clinical impacts of Blastocystis in cancer patients should be further examined, particularly as relates to treatment, microbiota and cancer type. PMID- 26905739 TI - Acceptability of Voluntary Medical Male Circumcision (VMMC) among Male Sexually Transmitted Diseases Patients (MSTDP) in China. AB - Voluntary Medical Male circumcision (VMMC) is an evidence-based, yet under utilized biomedical HIV intervention in China. No study has investigated acceptability of VMMC among male sexually transmitted diseases patients (MSTDP) who are at high risk of HIV transmission. A cross-sectional survey interviewed 350 HIV negative heterosexual MSTDP in Shenzhen, China; 12.0% (n = 42) of them were circumcised at the time of survey. When the uncircumcised participants (n = 308) were informed that VMMC could reduce the risk of HIV infection via heterosexual intercourse by 50%, the prevalence of acceptability of VMMC in the next six months was 46.1%. Adjusted for significant background variables, significant factors of acceptability of VMMC included: 1) emotional variables: the Emotional Representation Subscale (adjusted odds ratios, AOR = 1.13, 95%CI: 1.06-1.18), 2) cognitive variables derived from Health Belief Model (HBM): perceived some chance of having sex with HIV positive women in the next 12 months (AOR = 2.48, 95%CI: 1.15-5.33) (perceived susceptibility), perceived severity of STD infection (AOR = 1.06, 95%CI: 1.02-1.10), perceived benefit of VMMC in risk reduction (AOR = 1.29, 95%CI: 1.16-1.42) and sexual performance (AOR = 1.45, 95%CI: 1.26-1.71), perceived barriers against taking up VMMC (AOR = 0.88, 95%CI: 0.81-0.95), and perceived cue to action (AOR = 1.41, 95%CI: 1.23-1.61) and self efficacy (AOR = 1.38, 95%CI: 1.26-1.35) related to taking up VMMC. The association between perceived severity of STD infection and acceptability was fully mediated by emotional representation of STD infection. The relatively low prevalence of circumcision and high acceptability suggested that the situation was favorable for implementing VMMC as a means of HIV intervention among MSTDP in China. HBM is a potential suitable framework to guide the design of future VMMC promotion. Future implementation programs should be conducted in STD clinic settings, taking the important findings of this study into account. PMID- 26905741 TI - Microbial succession in response to pollutants in batch-enrichment culture. AB - As a global problem, environmental pollution is an important factor to shape the microbial communities. The elucidation of the succession of microbial communities in response to pollutants is essential for developing bioremediation procedures. In the present study, ten batches of soil-enrichment subcultures were subjected to four treatments: phenanthrene, n-octadecane, phenanthrene + n-octadecane, or phenanthrene + n-octadecane + CdCl2. Forty pollutant-degrading consortia, corresponding to each batch of the four treatments were obtained. High-throughput sequencing of the 16S rRNA gene revealed that the diversity, richness and evenness of the consortia decreased throughout the subculturing procedure. The well-known hydrocarbon degraders Acinetobacter, Gordonia, Sphingobium, Sphingopyxis, and Castellaniella and several other genera, including Niabella and Naxibacter, were detected in the enriched consortia. The predominant microbes varied and the microbial community in the consortia gradually changed during the successive subculturing depending on the treatment, indicating that the pollutants influenced the microbial successions. Comparison of the networks in the treatments indicated that organic pollutants and CdCl2 affected the co occurrence patterns in enriched consortia. In conclusion, single environmental factors, such as the addition of nutrients or selection pressure, can shape microbial communities and partially explain the extensive differences in microbial community structures among diverse environments. PMID- 26905742 TI - Developing Normal Turns-Amplitude Clouds for Upper and Lower Limbs. AB - PURPOSE: Turns and amplitude analysis (T&A) is a frequently used method for automatic EMG interference pattern analysis. The T&A normal values have only been developed for a limited number of muscles. Our objective was to obtain normal T&A clouds for upper and lower extremity muscles for which no normal values exist in the literature. METHODS: The T&A normative data using concentric needle electrodes were obtained from 68 men and 56 women aged 20 to 60 years. RESULTS: Normal upper and lower extremity T&A clouds were obtained and presented in this article. CONCLUSION: The T&A normal values collected in this study maybe used to detect neurogenic and myopathic abnormalities in men and women at low-to-moderate muscle contractions. The effect of turns-amplitude data obtained at high force level of muscle contraction and its potential to falsely show neurogenic abnormalities are discussed. PMID- 26905743 TI - The Glasgow Prognostic Score Predicts Response to Chemotherapy in Patients with Metastatic Breast Cancer. AB - PURPOSE: Breast cancer is one of the most common causes of cancer death in women worldwide. The Glasgow Prognostic Score (GPS), a cumulative prognostic score based on C-reactive protein and albumin, indicates the presence of a systemic inflammatory response. The GPS has been adopted as a powerful prognostic tool for patients with various types of malignant tumors, including breast cancer. The aim of this study was to assess the value of the GPS in predicting the response and toxicity in breast cancer patients treated with chemotherapy. PATIENTS AND METHODS: Patients with metastatic breast cancers in a progressive stage for consideration of chemotherapy were eligible. The clinical characteristics and demographics were recorded. The GPS was calculated before the onset of chemotherapy. Data on the response to chemotherapy and progression-free survival (PFS) were also collected. Objective tumor responses were evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST). Toxicities were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTC) version 3.0 throughout therapy. RESULTS: In total, 106 breast cancer patients were recruited. The GPS was associated with the response rate (p = 0.05), the clinical benefit rate (p = 0.03), and PFS (p = 0.005). The GPS was the only independent predictor of PFS (p = 0.005). The GPS was significantly associated with neutropenia, thrombocytopenia, anorexia, nausea and vomiting, fatigue, and mucositis (p = 0.05-0.001). CONCLUSIONS: Our data demonstrate that GPS assessment is associated with poor clinical outcomes and severe chemotherapy related toxicities in patients with metastatic breast cancer who have undergone chemotherapy, without any specific indication regarding the type of chemotherapy applied. PMID- 26905744 TI - Conjunctival leishmaniasis in a case of disseminated cutaneous leishmaniasis. AB - A 15-year-old female patient presented with numerous, small, papulonodular skin lesions, and hepatosplenomegaly 9 months after a treated biopsy proved cutaneous leishmaniasis. In ocular examination there were two yellowish, raised gelatinous conjunctival lesions in the left eye. The exisional conjunctival lesion biopsy revealed many Leishman bodies inside tissue histiocytes. The patient had no systemic immunologic problems (normal serum immunoglobulins, nitroblue tetrazolium test, complement CH50 test and flow cytometry of leukocytes). The indirect immunofluorescent antibody test for Leishmania tropica (titre of 1:1024) and the leishmanin skin test were positive. DNA of L. tropica was detected by a specific polymerase chain reaction on whole blood, bone marrow and skin biopsy specimens. The skin and conjunctival lesions disappeared with miltefosine and no intraocular tissue penetration of organism happened. Conjunctival leishmaniasis should be considered in the differential diagnosis of raised conjunctival lesions in a disseminated cutaneous leishmaniasis patient and needs proper systemic therapy. PMID- 26905745 TI - Corrigendum. AB - The correct title of the article with the DOI: 10.1177/0049475515585640, published in the January 2016 edition of Tropical Doctor, should read as. PMID- 26905747 TI - Prevalence of grade 1, 2 and 3 thinness is associated with lower socio-economic status in children in Shanghai, China. AB - OBJECTIVE: We aimed to investigate the prevalence of grade 1, 2 and 3 thinness among Chinese children and to explore their associations with socio-economic status (SES). DESIGN: A population, school-based cross-sectional study using multistage, stratified cluster random sampling. Grade 1, 2 and 3 thinness, overweight, obesity and severe obesity were defined by the International Obesity Task Force BMI cut-offs. SETTING: Seven districts of Shanghai, China. SUBJECTS: Chinese children aged 3-12 years (n 84 075). RESULTS: In boys and girls, respectively, the prevalence of grade 1 thinness was 8.89 % and 11.78 %, of grade 2 thinness was 2.80 % and 3.74 %, and of grade 3 thinness was 2.23 % and 2.93 %. Compared with urban children, suburban children had higher prevalence of thinness. Children whose parent had low education had higher prevalence of grade 1, 2 and 3 thinness than those whose parent had high education. The prevalence of grade 2 and 3 thinness, obesity and severe obesity in low-SES children was higher than that in high-SES children, and the prevalence of grade 1 thinness was lower than that in high-SES children. Particular patterns of prevalence of grade 1, 2 and 3 thinness appeared in low-, middle- and high-SES children. CONCLUSIONS: The study describes associations of SES with grade 1, 2 and 3 thinness, overweight, obesity and severe obesity in Shanghai children. The patterns of thinness and obesity in Shanghai provide further insights into BMI patterns in mega-cities in developing countries. PMID- 26905748 TI - Elevated nuclear sphingoid base-1-phosphates and decreased histone deacetylase activity after fumonisin B1 treatment in mouse embryonic fibroblasts. AB - Fumonisin B1 (FB1) is a mycotoxin produced by a common fungal contaminant of corn. Administration of FB1 to pregnant LM/Bc mice induces exencephaly in embryos, and ingestion of FB1-contaminated food during early pregnancy is associated with increased risk for neural tube defects (NTDs) in humans. FB1 inhibits ceramide synthase enzymes in sphingolipid biosynthesis, causing sphinganine (Sa) and bioactive sphinganine-1-phosphate (Sa1P) accumulation in blood, cells, and tissues. Sphingosine kinases (Sphk) phosphorylate Sa to form Sa1P. Upon activation, Sphk1 associates primarily with the plasma membrane, while Sphk2 is found predominantly in the nucleus. In cells over-expressing Sphk2, accumulation of Sa1P in the nuclear compartment inhibits histone deacetylase (HDAC) activity, causing increased acetylation of histone lysine residues. In this study, FB1 treatment in LM/Bc mouse embryonic fibroblasts (MEFs) resulted in significant accumulation of Sa1P in nuclear extracts relative to cytoplasmic extracts. Elevated nuclear Sa1P corresponded to decreased histone deacetylase (HDAC) activity and increased histone acetylation at H2BK12, H3K9, H3K18, and H3K23. Treatment of LM/Bc MEFs with a selective Sphk1 inhibitor, PF-543, or with ABC294640, a selective Sphk2 inhibitor, significantly reduced nuclear Sa1P accumulation after FB1, although Sa1P levels remained significantly increased relative to basal levels. Concurrent treatment with both PF-543 and ABC294640 prevented nuclear accumulation of Sa1P in response to FB1. Other HDAC inhibitors are known to cause NTDs, so these results suggest that FB1-induced disruption of sphingolipid metabolism leading to nuclear Sa1P accumulation, HDAC inhibition, and histone hyperacetylation is a potential mechanism for FB1-induced NTDs. PMID- 26905749 TI - Post-operative recurrence of Crohn's disease: A prospective study at 5 years. AB - BACKGROUND: We aimed to prospectively assess whether endoscopic recurrence severity at 1 year in Crohn's disease is predictive of clinical recurrence within 5 years. METHODS: Clinical recurrence (Crohn's Disease Activity Index>150) was assessed yearly for 5 years in Crohn's disease patients undergoing ileo-colonic resection. At 1 year, recurrence was assessed by colonoscopy (Rutgeerts' score >=i1 or >=2i) and small intestine contrast ultrasonography. RESULTS: 40 patients were included (23 males, median age 39 [16-69] years). Clinical recurrence occurred within 5 years in 16 (40%) patients (years 1, 2, 3, 4, 5: 2 [5%]; 10 [25%]; 4 [10%]; 2 [5%]; 4 [10%], respectively). At 1 year, endoscopic recurrence (score>=i1) occurred in 39 (97.5%) patients (score>=i2: 33 [82.5%]). Ultrasound detected lesions compatible with recurrence in 39/40 (97.5%) patients. Endoscopic score at 1 year was correlated with clinical score at 2 years (p=0.007; r=0.41). Endoscopic score at 1 year was higher in patients with (n=10) vs without (n=30) clinical recurrence at 2 years (3 [2-4] vs 2 [0-4]; p=0.003). Higher endoscopic score (>i2) at 1 year was a risk factor for clinical recurrence within 5 years (OR=0.18; 95% CI 0.04-0.71; p=0.008). CONCLUSIONS: In Crohn's disease, severity of endoscopic recurrence at 1 year remains a predictive marker of clinical recurrence within 5 years. Small intestine contrast ultrasonography is useful for assessing 1-year recurrence. PMID- 26905750 TI - Attachment in detachment: The positive role of caregivers in POWs' dissociative hallucinations. AB - Humans are social creatures and therefore exhibit a pervasive need for others. Hence, when benevolent human contact is scarce, this dearth may be compensated imaginatively. War captivity is an extreme example of such deprivation and one wherein dissociative hallucinations have been exhibited. Although hallucinations may serve to virtually summon benevolent others and thus provide the prisoner of war (POW) with a platform for compensation, the contents of such hallucinations have yet to be investigated. The current qualitative study is the first to examine whether the content of such hallucinations may harbor positive effects. Guided by the notion that people search for compensation in lack of companionship, we scrutinized testimonies of former POWs for accounts of hallucinatory experiences. A narrative analysis was utilized in an attempt to understand the meaning of the hallucinations for the POW. Findings reveal that benevolent figures and concomitant acts of care are exhibited in war captivity hallucinatory experiences. Thus, it is argued that the content of such hallucinations may be protective. These findings are discussed in light of the literature concerning peritraumatic dissociative experiences. In addition, attachment theory is suggested as a plausible framework for understanding these findings. Finally, limitations of the study are discussed, and future researched is suggested. PMID- 26905752 TI - Osteolytic changes around biodegradable cement restrictors in hip surgery. AB - Background and purpose - Biodegradable cement restrictors are widely used in hip arthroplasty. Like others, we observed osteolytic reactions associated with a specific cement restrictor (SynPlug; made of PolyActive) and reviewed our patients. Patients and methods - We identified 703 patients with suitable radiographs from our database (2007 to 2012) who underwent cemented hip arthroplasty and received a SynPlug biodegradable cement restrictor. We reviewed all available radiographs to determine the incidence, severity, and progression of osteolysis. Mean postoperative follow-up was 1.8 (1-7) years Results - 1 year after implantation, the femoral cortex showed thinning by 12% in the anterior posterior view and by 8% in the axial view. This had increased to 14% and 12%, respectively, at the latest available follow-up postoperatively (at a mean of 4 years). Cortical thinning of less than 10% was found in 37% of patients, but cortical thinning of 10-30% was found in 56% of patients. In the remaining 7%, a reduction of more than 30% of the original cortical thickness was observed. Interpretation - Osteolytic changes associated with the SynPlug biodegradable bone restrictors are inconsistent and highly variable. While some patients showed increased weakening of the femoral cortex with the potential risk of periprosthetic fracture, in others the degree of osteolysis only increased slightly or stabilized after 2 or more years. Any cortical bone loss after total hip replacement should be avoided, so the use of PolyActive biodegradable cement restrictors should be discontinued. Patients with a PolyActive cement restrictor in place should be followed up closely after surgery. PMID- 26905751 TI - Synthetic Capillaries to Control Microscopic Blood Flow. AB - Capillaries pervade human physiology. The mean intercapillary distance is only about 100 MUm in human tissue, which indicates the extent of nutrient diffusion. In engineered tissue the lack of capillaries, along with the associated perfusion, is problematic because it leads to hypoxic stress and necrosis. However, a capillary is not easy to engineer due to its complex cytoarchitecture. Here, it is shown that it is possible to create in vitro, in about 30 min, a tubular microenvironment with an elastic modulus and porosity consistent with human tissue that functionally mimicks a bona fide capillary using "live cell lithography"(LCL) to control the type and position of cells on a composite hydrogel scaffold. Furthermore, it is established that these constructs support the forces associated with blood flow, and produce nutrient gradients similar to those measured in vivo. With LCL, capillaries can be constructed with single cell precision-no other method for tissue engineering offers such precision. Since the time required for assembly scales with the number of cells, this method is likely to be adapted first to create minimal functional units of human tissue that constitute organs, consisting of a heterogeneous population of 100-1000 cells, organized hierarchically to express a predictable function. PMID- 26905754 TI - Optimizing conditions for utilization of an H2 oxidation catalyst with outer coordination sphere functionalities. AB - As a starting point for evaluating a broader range of conditions for H2 oxidation complexes, in this work we investigate an efficient and reversible Ni-based H2 oxidation and production complex with an arginine in the outer coordination sphere, [Ni(P(Cy)2N(Arginine)2)2](7+) (CyArg). We tested this complex under a wide range of pressures and temperatures, in two different solvents (methanol and water), to determine if simultaneous improvements in rate and overpotential could be achieved. We found that the optimal conditions combined both high temperature (72 degrees C) and pressure (100 atm H2) in acidic aqueous solution (pH = 1), resulting in the fastest H2 oxidation reported for any homogeneous electrocatalyst to date (TOF 1.1 * 10(6) s(-1)) operating at 240 mV overpotential. The activation free energy in water was determined to be 10 kcal mol(-1) at all pressures studied. Surprisingly, in methanol under the same temperature and pressure, CyArg had a TOF for H2 oxidation of only 280 s(-1) at an overpotential of 750 mV. Comparisons to the data in water, and to a control complex, [Ni(P(Cy)2N(Benzyl)2)2](2+) (CyBn; Bn = benzyl), suggest that this substantial difference is likely due to a change in rate limiting step from H2 addition to deprotonation. Importantly, the optimal conditions we identified for CyArg (elevated temperature and acidic aqueous solutions), are amenable to fuel cell technologies and provide an important advancement in implementing homogeneous synthetic catalysts for renewable energy. PMID- 26905753 TI - Large-scale evaluation of SLC18A2 in prostate cancer reveals diagnostic and prognostic biomarker potential at three molecular levels. AB - Limitations of current diagnostic and prognostic tools for prostate cancer (PC) have led to over-diagnosis and over-treatment. Here, we investigate the biomarker potential of the SLC18A2 (VMAT2) gene for PC at three molecular levels. Thus, SLC18A2 promoter methylation was analyzed in 767 malignant and 78 benign radical prostatectomy (RP) samples using methylation-specific qPCR and Illumina 450K methylation microarray data. SLC18A2 transcript levels were assessed in 412 malignant and 45 benign RP samples using RNAseq data. SLC18A2 protein was evaluated by immunohistochemistry in 502 malignant and 305 benign RP samples. Cancer-specificity of molecular changes was tested using Mann-Whitney U tests and/or receiver operating characteristic (ROC) analyses. Log rank, uni- and multivariate Cox regression tests were used for survival analyses. We found that SLC18A2 promoter hypermethylation was highly cancer-specific (area under the curve (AUC): 0.923-0.976) and associated with biochemical recurrence (BCR) after RP in univariate analyses. SLC18A2 transcript levels were reduced in PC and had independent prognostic value for BCR after RP (multivariate HR 0.13, P < 0.05). Likewise, SLC18A2 protein was down-regulated in PC (AUC 0.898) and had independent prognostic value for BCR (multivariate HR 0.51, P < 0.05). Reduced SLC18A2 protein expression was also associated with poor overall survival in univariate analysis (HR 0.29, P < 0.05). Our results highlight SLC18A2 as a new promising methylation marker candidate for PC diagnosis. Furthermore, SLC18A2 expression (RNA and protein) showed promising prognostic potential beyond routine clinicopathological variables. Thus, novel SLC18A2-based molecular tests could have useful future applications for PC detection and identification of high-risk patients. PMID- 26905755 TI - Perioperative Statins in Cardiac Surgery and Acute Kidney Injury. PMID- 26905756 TI - Syntheses of methylated catechins and theaflavins using 2-nitrobenzenesulfonyl group to protect and deactivate phenol. AB - An efficient and versatile synthetic method for labile polyphenols was established using 2-nitrobenzenesulfonate (Ns) as a protecting group for phenol. This methodology provides regio- and stereoselective access to a range of methylated catechins, such as methylated epigallocatechin gallates, that are not readily available from natural sources. In addition, biomimetic synthesis of theaflavins from catechins was accomplished using Ns protection to minimize undesired side reactions of electron-rich aromatic rings during oxidation, enabling construction of the complex benzotropolone core in a single-step oxidative coupling reaction. Availability of these compounds will aid detailed structure-biological activity relationship studies of catechins. PMID- 26905757 TI - Effect of different agents with potential antibiofilm activity on antimicrobial susceptibility of biofilms formed by Staphylococcus spp. isolated from implant related infections. AB - An in vitro study aimed to evaluate the effect of N-acetyl cysteine (NAC) or sub ICs of erythromycin on antimicrobial susceptibility of staphylococcal biofilms was performed. Staphylococcus aureus and Staphylococcus epidermidis strains were isolated from patients with prosthetic joint infections using a previously published sonication procedure. Conventional susceptibility studies were performed using microdilution according to the CLSI procedures. Biofilm susceptibility was performed using the Calgary methodology. The addition of NAC showed no effect with the S. aureus strains, and a strain-dependent effect with the S. epidermidis strains. No effect was detected with erythromycin for almost all tested strains. PMID- 26905758 TI - Cladosporinone, a new viriditoxin derivative from the hypersaline lake derived fungus Cladosporium cladosporioides. AB - A new cytotoxic viriditoxin derivative, cladosporinone (1), along with the known viriditoxin (2) and two viriditoxin derivatives (3 and 4) were obtained from the fungus Cladosporium cladosporioides isolated from the sediment of a hypersaline lake in Egypt. The structure of the new compound (1) was determined by 1D and 2D NMR measurements as well as by high-resolution ESIMS and electronic circular dichroism spectroscopy. All isolated compounds were studied for their cytotoxicity against the murine lymphoma cell line L5187Y and for their antibiotic activity against several pathogenic bacteria. Viriditoxin (2) was the most active compound in both bioassays. Compound 1 also exhibited strong cytotoxicity against the murine lymphoma cell line L5187Y with an IC50 value of 0.88 MUm, whereas its antibiotic activity was weak. PMID- 26905759 TI - Albaflavenoid, a new tricyclic sesquiterpenoid from Streptomyces violascens. PMID- 26905760 TI - Precursor-directed biosynthesis of new sansanmycin analogs bearing para substituted-phenylalanines with high yields. PMID- 26905761 TI - Reducing alcohol-related aggression: Effects of a self-awareness manipulation and locus of control in heavy drinking males. AB - Alcohol Myopia Theory (AMT; Steele & Josephs, 1990) purports that alcohol facilitates aggression by narrowing attentional focus onto salient and instigatory cues common to conflict situations. However, few tests of its counterintuitive prediction - that alcohol may decrease aggression when inhibitory cues are most salient - have been conducted. The present study examined whether an AMT-inspired self-awareness intervention manipulation would reduce heavy drinking men's intoxicated aggression toward women and also examined whether a relevant individual variable, locus of control, would moderate this effect. Participants were 102 intoxicated male heavy drinkers who completed a self-report measure of locus of control and completed the Taylor Aggression Paradigm (Taylor, 1967). In this task, participants administered electric shocks to, and received electric shocks from, a fictitious female opponent while exposed to an environment saturated with or devoid of self-awareness cues. Results indicated that the self-awareness manipulation was associated with less alcohol related aggression toward the female confederate for men who reported an internal, but not an external, locus of control. Findings support AMT as a theoretical framework to inform preventative interventions for alcohol-related aggression and highlight the importance of individual differences in receptivity to such interventions. PMID- 26905762 TI - A prospective, longitudinal study of cigarette smoking status among North American Indigenous adolescents. PMID- 26905763 TI - The relationship between gambling attitudes, involvement, and problems in adolescence: Examining the moderating role of coping strategies and parenting styles. AB - INTRODUCTION: Several factors are associated with an increased risk of adolescent problem gambling, including positive gambling attitudes, higher levels of gambling involvement, ineffective coping strategies and unhelpful parenting practices. It is less clear, however, how these factors interact or influence each other in the development of problem gambling behavior during adolescence. The aim of the current study was to simultaneously explore these predictors, with a particular focus on the extent to which coping skills and parenting styles may moderate the expected association between gambling involvement and gambling problems. METHODS: Participants were 612 high school students. The data were analyzed using a zero-inflated Poisson (ZIP) regression model, controlling for gender. RESULTS: Although several variables predicted the number of symptoms associated with problem gambling, none of them predicted the probability of displaying any problem gambling. Gambling involvement fully mediated the relationship between positive gambling attitudes and gambling problem severity. There was a significant relationship between gambling involvement and problems at any level of problem focused coping, reference to others and inconsistent discipline. However, adaptive coping styles employed by adolescents and consistent disciplinary practices by parents were buffers of gambling problems at low levels of adolescent gambling involvement, but failed to protect adolescents when their gambling involvement was high. CONCLUSIONS: These findings indicate that research exploring the development of gambling problems is required and imply that coping and parenting interventions may have particular utility for adolescents who are at risk of development gambling problems but who are not gambling frequently. PMID- 26905764 TI - Negative urgency and emotion regulation predict positive smoking expectancies in non-smoking youth. AB - INTRODUCTION: The purpose of the study was to better understand early risk for positive smoking expectancies, which have been shown to be consistent predictors of smoking initiation among youth. Two affect-based risk factors-negative urgency and emotion dysregulation-associated with smoking behaviors among youth, were examined for unique and interactive effects on positive smoking expectancies among substance-naive youth. METHODS: Participants were 61 10-14-year-old children with virtually no drug use (less than 5 substance use incidents across the lifetime), who were drawn from the community. RESULTS: Both negative urgency and emotion dysregulation were significantly associated with positive social facilitation smoking expectancies. Further, negative urgency was significantly related to positive social facilitation smoking expectancies at higher levels of emotion dysregulation (b=.09, p=.001). CONCLUSION: The findings provide evidence that both emotion dysregulation and negative urgency are positively associated with positive social-related smoking expectancies among a sample of 10-14-year olds. Children who are emotionally dysregulated and who act rashly in response to negative emotions appear more likely to endorse beliefs regarding the socially enhancing effects of smoking, suggesting that these youth may be at high risk for smoking initiation. PMID- 26905766 TI - WITHDRAWN: Functional capacity evaluations for the prevention of occupational re injuries in injured workers. PMID- 26905765 TI - Caffeinated and non-caffeinated alcohol use and indirect aggression: The impact of self-regulation. AB - Research shows that heavier alcohol use is associated with physical aggression. Scant research has examined the way in which alcohol relates to other forms of aggression, such as indirect aggression (e.g., malicious humor, social exclusion). Given the possible negative consequences of indirect aggression and the limited evidence suggesting alcohol use can elicit indirectly aggressive responses, research is needed to further investigate the association between drinking behavior and indirect aggression. Additionally, specific alcoholic beverages, such as caffeinated alcoholic beverages (CABs; e.g., Red Bull and vodka), may potentiate aggression above the influence of typical use, and thus warrant examination with regard to indirect aggression. One factor that may impact the strength of the alcohol-indirect aggression and CAB-indirect aggression relationships is one's level of self-regulation. Consequently, our study examined the relationships between (1) alcohol use and indirect aggression, (2) CAB use and indirect aggression, and (3) self-regulation as a moderator. Participants were 733 (67.6% female) undergraduate students who reported their CAB and alcohol use, self-regulation, and aggressive behaviors. Results revealed that heavier alcohol use was associated with more frequent indirect aggression after controlling for dispositional aggression. Heavier CAB use was related to more frequent indirect aggression after accounting for typical use and dispositional aggression. Self-regulation moderated these associations such that for those with lower self-regulation, greater alcohol and CAB consumption was associated with greater indirect aggression. Our findings suggest that heavier alcohol and CAB consumption may be risk factors for engaging in indirect aggression and this risk is impacted by one's regulatory control. PMID- 26905767 TI - Innate immune receptor Toll-like receptor 4 signalling in neuropsychiatric diseases. AB - The innate immunity is a stereotyped first line of defense against pathogens and unspecified damage signals. One of main actors of innate immunity are the Toll like receptors (TLRs), and one of the better characterized members of this family is TLR-4, that it is mainly activated by Gram-negative bacteria lipopolysaccharide. In brain, TLR-4 organizes innate immune responses against infections or cellular damage, but also possesses other physiological functions. In the last years, some evidences suggest a role of TLR-4 in stress and stress related neuropsychiatric diseases. Peripheral and brain TLR-4 activation triggers sickness behavior, and its expression is a risk factor of depression. Some elements of the TLR-4 signaling pathway are up-regulated in peripheral samples and brain post-mortem tissue from depressed and suicidal patients. The "leaky gut" hypothesis of neuropsychiatric diseases is based on the existence of an increase of the intestinal permeability which results in bacterial translocation able to activate TLR-4. Enhanced peripheral TLR-4 expression/activity has been described in subjects diagnosed with schizophrenia, bipolar disorder and in autistic children. A role for TLR-4 in drugs abuse has been also proposed. The therapeutic potential of pharmacological/genetic modulation of TLRs signaling pathways in neuropsychiatry is promising, but a great preclinical/clinical scientific effort is still needed. PMID- 26905768 TI - Graphene quantum dots as a highly efficient solution-processed charge trapping medium for organic nano-floating gate memory. AB - A highly efficient solution-processible charge trapping medium is a prerequisite to developing high-performance organic nano-floating gate memory (NFGM) devices. Although several candidates for the charge trapping layer have been proposed for organic memory, a method for significantly increasing the density of stored charges in nanoscale layers remains a considerable challenge. Here, solution processible graphene quantum dots (GQDs) were prepared by a modified thermal plasma jet method; the GQDs were mostly composed of carbon without any serious oxidation, which was confirmed by x-ray photoelectron spectroscopy. These GQDs have multiple energy levels because of their size distribution, and they can be effectively utilized as charge trapping media for organic NFGM applications. The NFGM device exhibited excellent reversible switching characteristics, with an on/off current ratio greater than 10(6), a stable retention time of 10(4) s and reliable cycling endurance over 100 cycles. In particular, we estimated that the GQDs layer trapped ~7.2 * 10(12) cm(-2) charges per unit area, which is a much higher density than those of other solution-processible nanomaterials, suggesting that the GQDs layer holds promise as a highly efficient nanoscale charge trapping material. PMID- 26905769 TI - Aerobic degradation of ibuprofen in batch and continuous reactors by an indigenous bacterial community. AB - Water from six points from the Riachuelo-Matanza basin was analyzed in order to assess ibuprofen biodegradability. In four of them biodegradation of ibuprofen was proved and degrading bacterial communities were isolated. Biodegradation in each point could not be correlated with sewage pollution. The indigenous bacterial community isolated from the point localized in the La Noria Bridge showed the highest degradative capacity and was selected to perform batch and continuous degradation assays. The partial 16S rRNA gene sequence showed that the community consisted of Comamonas aquatica and Bacillus sp. In batch assays the community was capable of degrading 100 mg L(-1) of ibuprofen in 33 h, with a specific growth rate (MU) of 0.21 h(-1). The removal of the compound, as determined by High performance liquid chromatography (HPLC), exceeded 99% of the initial concentration, with a 92.3% removal of Chemical Oxygen Demand (COD). In a down-flow fixed-bed continuous reactor, the community shows a removal efficiency of 95.9% of ibuprofen and 92.3% of COD for an average inlet concentration of 110.4 mg. The reactor was kept in operation for 70 days. The maximal removal rate for the compound was 17.4 g m(-3) d(-1). Scanning electron microscopy was employed to observe biofilm development in the reactor. The ability of the isolated indigenous community can be exploited to improve the treatment of wastewaters containing ibuprofen. PMID- 26905770 TI - Hypoalbuminemic edema, retroauricular swelling and severe eosinophilia: What is the missing link? PMID- 26905771 TI - Macroglossia and periorbital ecchymosis. PMID- 26905772 TI - Headache in a patient with renal cell carcinoma. PMID- 26905773 TI - Three cases of odontological foreign body bronchoaspiration. PMID- 26905774 TI - Black fiberoptic bronchoscopy after a fire. PMID- 26905775 TI - Mortality in elderly patients with community-acquired pneumonia. PMID- 26905776 TI - Evolution, diagnosis and treatment of elderly subjects with thoracic sarcoidosis: Report of 6 cases. PMID- 26905777 TI - Prevalence, Knowledge and Attitudes Towards Smoking Among SEPAR Members. AB - The aims of this study were to estimate the prevalence of smoking among SEPAR members, and their approach to smoking cessation in their patients. An online survey was completed by 640 members (496 pulmonologists, 45 nurses, 34 thoracic surgeons, 37 physiotherapists, and 28 other specialists). Of the members interviewed, 5% confessed that they were smokers: 3.5% pulmonologists; 8.9% nurses; 8.8% thoracic surgeons, and 13.5% physiotherapists. A total of 96% of members assign a lot or quite a lot of importance to setting an example; 98% of members always or often ask their patients about their smoking habit. The most effective anti-smoking intervention, according to 77% of members, is a combination of drugs and psychological support. These results are an indicator of the awareness and commitment of SEPAR members to smoking and its cessation. PMID- 26905778 TI - Obsolete anti-pneumoccal vaccination recommendations in the Spanish guidelines for the management of asthma (GEMA 4.0). PMID- 26905779 TI - Tunable Nanopatterning of Conductive Polymers via Electrohydrodynamic Lithography. AB - An increasing number of technologies require the fabrication of conductive structures on a broad range of scales and over large areas. Here, we introduce advanced yet simple electrohydrodynamic lithography (EHL) for patterning conductive polymers directly on a substrate with high fidelity. We illustrate the generality of this robust, low-cost method by structuring thin polypyrrole films via electric-field-induced instabilities, yielding well-defined conductive structures with feature sizes ranging from tens of micrometers to hundreds of nanometers. Exploitation of a conductive polymer induces free charge suppression of the field in the polymer film, paving the way for accessing scale sizes in the low submicron range. We show the feasibility of the polypyrrole-based structures for field-effect transistor devices. Controlled EHL pattering of conductive polymer structures at the micro and nano scale demonstrated in this study combined with the possibility of effectively tuning the dimensions of the tailor made architectures might herald a route toward various submicron device applications in supercapacitors, photovoltaics, sensors, and electronic displays. PMID- 26905781 TI - Erratum: Obesity changes the human gut mycobiome. PMID- 26905782 TI - Atomic-Scale Structure and Local Chemistry of CoFeB-MgO Magnetic Tunnel Junctions. AB - Magnetic tunnel junctions (MTJs) constitute a promising building block for future nonvolatile memories and logic circuits. Despite their pivotal role, spatially resolving and chemically identifying each individual stacking layer remains challenging due to spatially localized features that complicate characterizations limiting understanding of the physics of MTJs. Here, we combine advanced electron microscopy, spectroscopy, and first-principles calculations to obtain a direct structural and chemical imaging of the atomically confined layers in a CoFeB-MgO MTJ, and clarify atom diffusion and interface structures in the MTJ following annealing. The combined techniques demonstrate that B diffuses out of CoFeB electrodes into Ta interstitial sites rather than MgO after annealing, and CoFe bonds atomically to MgO grains with an epitaxial orientation relationship by forming Fe(Co)-O bonds, yet without incorporation of CoFe in MgO. These findings afford a comprehensive perspective on structure and chemistry of MTJs, helping to develop high-performance spintronic devices by atomistic design. PMID- 26905780 TI - Diversity of Sarcocystis spp shed by opossums in Brazil inferred with phylogenetic analysis of DNA coding ITS1, cytochrome B, and surface antigens. AB - Although few species of Sarcocystis are known to use marsupials of the genus Didelphis as definitive host, an extensive diversity of alleles of surface antigen genes (sag2, sag3, and sag4) has been described in samples of didelphid opossums in Brazil. In this work, we studied 25 samples of Sarcocystis derived from gastrointestinal tract of opossums of the genus Didelphis by accessing the variability of sag2, sag3, sag4, gene encoding cytochrome b (cytB) and first internal transcribed spacer (ITS1). Reference samples of Sarcocystis neurona (SN138) and Sarcocystis falcatula (SF1) maintained in cell culture were also analyzed. We found four allele variants of cytB, seven allele variants of ITS1, 10 allele variants of sag2, 13 allele variants of sag3, and 6 allele variants of sag4. None of the sporocyst-derived sequences obtained from Brazilian opossums revealed 100% identity to SN138 at cytB gene, nor to SN138 or SF1 at ITS1 locus. In addition, none of the sag alleles were found identical to either SF1 or SN138 homologous sequences, and a high number of new sag allele types were found other than those previously described in Brazil. Out of ten sag2 alleles, four are novel, while eight out of 13 sag3 alleles are novel and one out of six sag4 alleles is novel. Further studies are needed to clarify if such a vast repertoire of allele variants of Sarcocystis is the consequence of re-assortments driven by sexual exchange, in order to form individuals with highly diverse characteristics, such as pathogenicity, host spectrum, among others or if it only represents allele variants of different species with different biological traits. PMID- 26905783 TI - Wetting and cavitation pathways on nanodecorated surfaces. AB - In this contribution we study the wetting and nucleation of vapor bubbles on nanodecorated surfaces via free energy molecular dynamics simulations. The results shed light on the stability of superhydrophobicity in submerged surfaces with nanoscale corrugations. The re-entrant geometry of the cavities under investigation is capable of sustaining a confined vapor phase within the surface roughness (Cassie state) both for hydrophobic and hydrophilic combinations of liquid and solid. The atomistic system is of nanometric size; on this scale thermally activated events can play an important role ultimately determining the lifetime of the Cassie state. Such a superhydrophobic state can break down by full wetting of the texture at large pressures (Cassie-Wenzel transition) or by nucleating a vapor bubble at negative pressures (cavitation). Specialized rare event techniques show that several pathways for wetting and cavitation are possible, due to the complex surface geometry. The related free energy barriers are of the order of 100kBT and vary with pressure. The atomistic results are found to be in semi-quantitative accord with macroscopic capillarity theory. However, the latter is not capable of capturing the density fluctuations, which determine the destabilization of the confined liquid phase at negative pressures (liquid spinodal). PMID- 26905784 TI - Broad Consent for Genomic Research and Biobanking: Perspectives from Low- and Middle-Income Countries. AB - Genomic research and biobanking are increasingly being conducted in the context of collaborations between researchers in high-income countries and those in low- and middle-income countries. Although these scientific advancements have presented unique opportunities for researchers to contribute to cutting-edge scientific projects and address important health problems, they have also challenged existing ethical and regulatory frameworks, particularly in sub Saharan Africa. Broad consent is a model that allows the use of human biological samples and associated data in future research that may be unrelated to the original study. Drawing on emerging perspectives in low- and middle-income countries, we argue that broad consent is equivalent to consent to governance and that a robust governance framework for genomics and biobanking should seek to promote global health and research equity and take into account five key elements: respect, authentic community engagement and trust building, the preservation of privacy and confidentiality, feedback of results, and capacity strengthening. PMID- 26905785 TI - Cystic Fibrosis and Its Management Through Established and Emerging Therapies. AB - Cystic fibrosis (CF) is the most common life-shortening autosomal recessive disorder in the Caucasian population and occurs in many other ethnicities worldwide. The daily treatment burden is substantial for CF patients even when they are well, with numerous pharmacologic and physical therapies targeting lung disease requiring the greatest time commitment. CF treatments continue to advance with greater understanding of factors influencing long-term morbidity and mortality. In recent years, in-depth understanding of genetic and protein structure-function relationships has led to the introduction of targeted therapies for patients with specific CF genotypes. With these advances, CF has become a model of personalized or precision medicine. The near future will see greater access to targeted therapies for most patients carrying common mutations, which will mandate individualized bench-to-bedside methodologies for those with rare genotypes. PMID- 26905786 TI - Long-term effect of orthokeratology on the anterior segment length. AB - PURPOSE: To compare the effects of normal growth and longer term use of orthokeratology (ortho-k) on ocular biometric parameters in the anterior segment, including central corneal thickness (CCT), anterior chamber depth (ACD), crystalline lens thickness (CLT), and anterior segment length (ASL). METHODS: Baseline and six monthly data were retrieved from 78 subjects (aged 7-10 years, with myopia<=4.00D and astigmatism<=1.25D) who had completed a two-year randomized clinical trial using ortho-k for myopia control. They were randomly assigned to wear ortho-k lenses or single-vision spectacles (control). Anterior segment parameters were measured with the Pentacam after cycloplegia. RESULTS: No significant changes in CLT and ASL over time were observed in either group of subjects (37 ortho-k; 38 control). In the control group, CCT remained unchanged during the study period but in the ortho-k group, it was significantly reduced by an average of 0.009mm by the 6-month visit (p<0.001) and remained unchanged thereafter. No significant changes in ACD was found in the ortho-k group but it was significantly increased by an average of 0.04mm (p=0.001) in the control group. CONCLUSION: CLT nor ASL did not change over time in either control or ortho-k subjects. Although ACD significantly increased in the control subjects and CCT significantly reduced in the first six months of ortho-k lens wear, these changes were small and did not affect the overall ASL. PMID- 26905787 TI - Incidence and Remission of Nocturia: A Systematic Review and Meta-analysis. AB - CONTEXT: Although vital for decision-making about management, the natural history of nocturia remains uncertain. A systematic review would clarify the issue, but because natural history reviews are uncommon it would require methodological innovations. OBJECTIVE: To estimate the incidence and remission of nocturia, and refine methods for meta-analyses assessing natural history. EVIDENCE ACQUISITION: We conducted a comprehensive search of PubMed, Scopus, and Cumulative Index of Nursing and Allied Health Literature databases and abstracts of major urologic meetings as far as August 31, 2015. Random effects meta-analyses addressed incidence/remission rates of nocturia; meta-regression explored potential determinants of heterogeneity. Studies were categorized as either low or high risk of bias using a novel instrument specifically designed for longitudinal symptom studies aimed at the general population. EVIDENCE SYNTHESIS: Of 4165 potentially relevant reports, 16 proved eligible. Pooled estimates from 13 studies (114 964 person-years of follow-up) demonstrated that annual incidence was strongly associated with age: 0.4% (0-0.8%) for adults aged < 40 yr; 2.8% (1.9-3.7%) for adults aged 40-59 yr; and 11.5% (9.1-14.0%) for adults aged >= 60 yr. Of those with nocturia, each year 12.1% (9.5-14.7%) experienced remission. CONCLUSIONS: The available evidence suggests that nocturia onset is strongly associated with age, with much higher rates in those over 60 yr; remission occurs in approximately 12% each year. These estimates can aid with management decisions and counseling related to nocturia. PATIENT SUMMARY: We reviewed all previous studies of progression of night-time urination (nocturia). We found that in any given year 0.4% of adults aged < 40 yr, 3% of adults aged 40-59 yr, and 12% of adults aged >= 60 yr will develop nocturia, while overall 12% of those with nocturia will improve. These findings may be helpful in making decisions about coping with or treating nocturia. PMID- 26905789 TI - Use of a portable air disinfecting system to remove seeded coliphage in hospital rooms. AB - Health care-associated infections are a major problem worldwide, and the airborne route is believed to be a contributory source of secondary health care-associated infections. This study examined the efficacy of a portable air disinfecting system to remove seeded coliphage virus from the air in hospitals rooms. Aerosolized coliphage concentrations were not statistically different between treatment and no treatment measurements. However, future research should focus on additional investigations in the patient rooms that incorporate fomite and air testing alongside portable air filtration devices. PMID- 26905788 TI - Using Sensors and Generators of H2O2 to Elucidate the Toxicity Mechanism of Piperlongumine and Phenethyl Isothiocyanate. AB - AIMS: Chemotherapeutics target vital functions that ensure survival of cancer cells, including their increased reliance on defense mechanisms against oxidative stress compared to normal cells. Many chemotherapeutics exploit this vulnerability to oxidative stress by elevating the levels of intracellular reactive oxygen species (ROS). A quantitative understanding of the oxidants generated and how they induce toxicity will be important for effective implementation and design of future chemotherapeutics. Molecular tools that facilitate measurement and manipulation of individual chemical species within the context of the larger intracellular redox network present a means to develop this understanding. In this work, we demonstrate the use of such tools to elucidate the roles of H2O2 and glutathione (GSH) in the toxicity mechanism of two ROS based chemotherapeutics, piperlongumine and phenethyl isothiocyanate. RESULTS: Depletion of GSH as a result of treatment with these compounds is not an important part of the toxicity mechanisms of these drugs and does not lead to an increase in the intracellular H2O2 level. Measuring peroxiredoxin-2 (Prx-2) oxidation as evidence of increased H2O2, only piperlongumine treatment shows elevation and it is GSH independent. Using a combination of a sensor (HyPer) along with a generator (D-amino acid oxidase) to monitor and mimic the drug induced H2O2 production, it is determined that H2O2 produced during piperlongumine treatment acts synergistically with the compound to cause enhanced cysteine oxidation and subsequent toxicity. The importance of H2O2 elevation in the mechanism of piperlongumine promotes a hypothesis of why certain cells, such as A549, are more resistant to the drug than others. INNOVATION AND CONCLUSION: The approach described herein sheds new light on the previously proposed mechanism of these two ROS-based chemotherapeutics and advocates for the use of both sensors and generators of specific oxidants to isolate their effects. Antioxid. Redox Signal. 24, 924-938. PMID- 26905790 TI - Intestinal microbiome disruption in patients in a long-term acute care hospital: A case for development of microbiome disruption indices to improve infection prevention. AB - BACKGROUND: Composition and diversity of intestinal microbial communities (microbiota) are generally accepted as a risk factor for poor outcomes; however, we cannot yet use this information to prevent adverse outcomes. METHODS: Stool was collected from 8 long-term acute care hospital patients experiencing diarrhea and 2 fecal microbiota transplant donors; 16S rDNA V1-V2 hypervariable regions were sequenced. Composition and diversity of each sample were described. Stool was also tested for Clostridium difficile, vancomycin-resistant enterococci (VRE), and carbapenem-resistant Enterobacteriaceae. Associations between microbiota diversity and demographic and clinical characteristics, including antibiotic use, were analyzed. RESULTS: Antibiotic exposure and Charlson Comorbidity Index were inversely correlated with diversity (Spearman = -0.7). Two patients were positive for VRE; both had microbiomes dominated by Enterococcus faecium, accounting for 67%-84% of their microbiome. CONCLUSIONS: Antibiotic exposure correlated with diversity; however, other environmental and host factors not easily obtainable in a clinical setting are also known to impact the microbiota. Therefore, direct measurement of microbiome disruption by sequencing, rather than reliance on surrogate markers, might be most predictive of adverse outcomes. If and when microbiome characterization becomes a standard diagnostic test, improving our understanding of microbiome dynamics will allow for interpretation of results to improve patient outcomes. PMID- 26905791 TI - Evaluation of an ethical method aimed at improving hygiene rules compliance in dental practice. AB - BACKGROUND: The objective of this study is to determine the efficiency of an ethical method, based on a thought experiment in ethics, on hygiene rules compliance for dental health care team members. METHODS: This is a prospective study that assesses hygiene compliance in dental practice before and after a thought experiment in ethics, using 2 questionnaires. Participants included 130 clinician students in dentistry at Strasbourg University Hospital, France. RESULTS: The results emphasize a better implementation of hygiene rules after the thought experiment in ethics, when comparing the relative frequencies of completed hygiene items. A Wilcoxon signed-rank test shows significant differences between the first questionnaire and the second one after the thought experiment in ethics (P < .001). CONCLUSIONS: This ethical method provides efficiency on hygiene rules compliance, which makes it beneficial to implement. However, far from being an absolute unit method, this thought experiment in ethics appears to be an original, supplemental, and complementary method. PMID- 26905792 TI - Antibiotic information application offers nurses quick support. AB - BACKGROUND: Nurses can be crucial contributors to antibiotic stewardship programs (ASPs), interventions aimed at improving antibiotic use, but nurse empowerment in ASPs adds to their job complexity. Nurses work in complex settings with high cognitive loads, which ask for easily accessible information. An information application (app) was developed to support nurses in ASPs. The efficiency, effectiveness, and user satisfaction regarding this antibiotic app were tested in a pilot study. METHODS: The app was introduced into 2 lung wards of a local teaching hospital. During the 8-month pilot study, the 62 nurses of the wards had access to the app. Changes in user satisfaction regarding information support, safety attitudes, and ASP behavior were assessed with a questionnaire. At baseline, 28 nurses completed the (e-mail) questionnaire; after the study, 18 nurses participated. Scenario-based tests were done to assess app efficiency and effectiveness at baseline (n = 16) and in a randomized control (without the app, n = 17) and intervention condition (with the app, n = 17). RESULTS: Significant improvements were found regarding task support (P = .041), reliability (P = .004), unobtrusiveness (P = .000), relevance (P = .002), user friendliness (P = .000), speed, and hyperlinks (P = .001). An improvement in communication was observed regarding nurse-physician understanding (P = .034). With the app, nurses solved the scenarios faster than without it. CONCLUSIONS: The human-centered design approach and persuasive strategy of task support were effective in reducing time needed to find information. Stewardship-related behaviors need active education strategies. PMID- 26905794 TI - Symptom profile of alcohol withdrawal delirium: factor analysis of Delirium Rating Scale-Revised-98 version. AB - BACKGROUND: The symptom profile of alcohol withdrawal delirium (AWD), relative to deliriums of other etiology, remains uncertain. OBJECTIVE: To evaluate the factor structure of symptoms in patients with AWD, as assessed by the Delirium Rating Scale-Revised-98 (DRS-R-98). METHOD: A total of 112 patients aged 18 years or more with AWD were assessed on DRS-R-98. RESULTS: The mean age of participants was 44.2 years. About two-third of the patients developed delirium within 24 hours of the last intake of alcohol and the mean duration of delirium at the time of assessment was 3.9 days. In 46% of cases the delirium was attributed solely to alcohol withdrawal; in the remaining subjects alcohol withdrawal was a major contributory factor. Three separate principal component analysis (whole sample, pure AWD and AWD with associated etiologies) were carried out. In all the factor analyses, one of the factors included cognitive symptoms (attention, orientation and visuospatial disturbances) along with or without short- and long-term memory impairment; the second factor included motoric symptoms along with sleep-wake cycle disturbances; the third factor included psychotic symptoms. For the whole group and subgroup of AWD with associated etiologies, items of higher level thinking (i.e. language disturbances and thought process abnormality) loaded along with cognitive symptoms. In pure AWD group, these items along with memory disturbances loaded with psychotic symptoms. CONCLUSIONS: Results of the current factor analyses suggest that the factor structure of pure AWD is different from AWD with associated etiologies. Hence, attention to the symptom profile of patients with AWD may provide clues to delirium etiology. PMID- 26905795 TI - Conversion of L-lactate into n-caproate by a continuously fed reactor microbiome. AB - Conversion of lactate to n-caproate had been described for the type strain Megasphaera elsdenii in batch systems. Recently, investigators have also described production of n-caproate from endogenous or exogenous lactate with batch-fed reactor microbiome systems. However, no reports exist of lactate to n caproate conversion within a continuously fed bioreactor. Since continuously fed systems are advantageous for biotechnology production platforms, our objective was to develop such a system. Here, we demonstrated continuous lactate to n caproate conversion for more than 165 days. The volumetric n-caproate production rate (productivity) was improved when we decreased the operating pH from 5.5 to 5.0, and was again improved when we utilized in-line product recovery via pertraction (membrane-based liquid-liquid extraction). We observed a maximum n caproate productivity of 6.9 g COD/L-d for a period of 17 days at an L-lactate loading rate of 9.1 g COD/L-d, representing the highest sustained lactate to n caproate conversion rate ever reported. We had to manage two competing lactate conversion pathways: 1) the reverse beta-oxidation pathway to n-caproate; and 2) the acrylate pathway to propionate. We found that maintaining a low residual lactate concentration in the bioreactor broth was necessary to direct lactate conversion towards n-caproate instead of propionate. These findings provide a foundation for the development of new resource recovery processes to produce higher-value liquid products (e.g., n-caproate) from carbon-rich wastewaters containing lactate or lactate precursors (e.g., carbohydrates). PMID- 26905796 TI - Rejection of pharmaceutically-based N-nitrosodimethylamine precursors using nanofiltration. AB - N-Nitrosodimethylamine (NDMA) is a disinfection by-product (DBP) with many known precursors such as amine-containing pharmaceuticals that can enter the environment via treated wastewater. Reverse osmosis and tight nanofiltration membranes (MW cutoff < 200 Da) are treatment technologies that demonstrate high removal of many compounds, but at relatively high energy costs. Looser membranes (>200 Da) may provide sufficient removal of a wide range of contaminants with lower energy costs. This study examined the rejection of pharmaceuticals that are known NDMA precursors (~300 Da) using nanofiltration (MW cutoff ~350 Da). MQ water was compared to two raw water sources, and results illustrated that NDMA precursors (as estimated by formation potential testing) were effectively rejected in all water matrices (>84%). Mixtures of pharmaceuticals vs. single spiked compounds were found to have no impact on rejection from the membranes used. The use of MQ water vs. surface waters illustrated that natural organic matter, colloids, and inorganic ions present did not significantly impact the rejection of the amine-containing pharmaceuticals. This study illustrates that NDMA formation potential testing can be effectively used for assessing NDMA precursor rejection from more complex samples with multiple and/or unknown NDMA precursors present, such as wastewater matrices. PMID- 26905797 TI - An ecological new approach for treating Cr(VI)-containing industrial wastewater: Photochemical reduction. AB - An ecological new approach for photochemical reduction of Cr(VI) in aqueous solution by adding into water-soluble copolymer, polyethylene glycol (PEG), was investigated. Various influences including light intensity, initial solution pH value, PEG molecular weight and initial concentration ratio of PEG to Cr(VI) on photochemical reduction of Cr(VI) were discussed, and a possible reaction mechanism was proposed. Experimental results revealed that Cr(VI) could be reduced to Cr(III) by PEG under sunlight irradiation. The photo-reduction rate of Cr(VI) increased with the decrease of solution pH and PEG molecular weight, but increased with the light intensity. The reduction percentage of Cr(VI) increased with the initial concentration ratio of PEG to Cr(VI). When the initial solution pH value was below 3.0, almost all of Cr(VI) was completely reduced to Cr(III) within 20 min of 50 * 10(3) lux solar irradiation in the presence of PEG. After photo-reduction, PEG and Cr(III) in aqueous solutions could be recovered by adding into a high-concentrated Na2SO4 aqueous solution to induce the formation of a stable PEG-based aqueous biphasic system. By doing so, Na2SO4 in aqueous solution could also be removed. The present work highlights a promising new route for treating the industrial wastewater containing toxic Cr(VI) ions by adding into environmental-friendly PEG for photo-reduction of Cr(VI) to Cr(III), and then salting-out recovery of PEG and removal of Cr(III) in wastewater by adding into another high-salt wastewater, so that the high-salt wastewater could also be treated. PMID- 26905798 TI - New insights into the fouling mechanism of dissolved organic matter applying nanofiltration membranes with a variety of surface chemistries. AB - Nanofiltration (NF) membrane fouling by DOM remains a major and poorly understood issue. To acquire a better insight we studied the fouling of the DOM fractions humic acids (HAs) and fulvic acids (FAs), with and without Ca(2+), on native and grafted ceramic NF membranes. Grafting with two methods and three different grafting groups allowed to create a range of membranes with a variety of surface chemistries, and a wide range of surface polarity, much broader than ever used in previous studies. A typical polymer (polyamide) NF membrane was included for comparison. All obtained results reveal that membrane fouling is not determined by membrane hydrophilicity/hydrophobicity as a general and sole criterion, but rather on the whole of the surface chemistry determining the amount and strength of the possible foulant-membrane interactions. As a consequence the effect of inorganic ions on the fouling is also dependent on the surface chemistry. Important new insight in the DOM fouling mechanism was acquired, shedding new light on the state-of-the-art knowledge. PMID- 26905799 TI - Reducing aeration energy consumption in a large-scale membrane bioreactor: Process simulation and engineering application. AB - Reducing the energy consumption of membrane bioreactors (MBRs) is highly important for their wider application in wastewater treatment engineering. Of particular significance is reducing aeration in aerobic tanks to reduce the overall energy consumption. This study proposed an in situ ammonia-N-based feedback control strategy for aeration in aerobic tanks; this was tested via model simulation and through a large-scale (50,000 m(3)/d) engineering application. A full-scale MBR model was developed based on the activated sludge model (ASM) and was calibrated to the actual MBR. The aeration control strategy took the form of a two-step cascaded proportion-integration (PI) feedback algorithm. Algorithmic parameters were optimized via model simulation. The strategy achieved real-time adjustment of aeration amounts based on feedback from effluent quality (i.e., ammonia-N). The effectiveness of the strategy was evaluated through both the model platform and the full-scale engineering application. In the former, the aeration flow rate was reduced by 15-20%. In the engineering application, the aeration flow rate was reduced by 20%, and overall specific energy consumption correspondingly reduced by 4% to 0.45 kWh/m(3) effluent, using the present practice of regulating the angle of guide vanes of fixed-frequency blowers. Potential energy savings are expected to be higher for MBRs with variable-frequency blowers. This study indicated that the ammonia-N based aeration control strategy holds promise for application in full-scale MBRs. PMID- 26905800 TI - Hybrid biological, electron beam and zero-valent nano iron treatment of recalcitrant metalworking fluids. AB - Hybrid approaches for the remediation and detoxification of toxic recalcitrant industrial wastewater were investigated. The focus was waste metalworking fluid, which was selected as a representative model of other waste streams that are toxic, recalcitrant and that require more sustainable routes of safe disposal. The hybrid approaches included biodegradation, electron beam irradiation and zero valent nano iron advanced oxidation processes that were employed individually and in sequence employing a factorial design. To compare process performance operationally exhausted and pristine metalworking fluid were compared. Sequential hybrid electron beam irradiation, biological, nanoscale zero-valent iron and biological treatment lead to synergistic detoxification and degradation of both recalcitrant streams, as determined by complementary surrogates and lead to overall improved COD removal of 92.8 +/- 1.4% up from 85.9 +/- 3.4% for the pristine metalworking fluid. Electron beam pre-treatment enabled more effective biotreatment, achieving 69.5 +/- 8% (p = 0.005) and 24.6 +/- 4.8% (p = 0.044) COD reductions. PMID- 26905801 TI - Why conventional detection methods fail in identifying the existence of contamination events. AB - Early warning systems are widely used to safeguard water security, but their effectiveness has raised many questions. To understand why conventional detection methods fail to identify contamination events, this study evaluates the performance of three contamination detection methods using data from a real contamination accident and two artificial datasets constructed using a widely applied contamination data construction approach. Results show that the Pearson correlation Euclidean distance (PE) based detection method performs better for real contamination incidents, while the Euclidean distance method (MED) and linear prediction filter (LPF) method are more suitable for detecting sudden spike-like variation. This analysis revealed why the conventional MED and LPF methods failed to identify existence of contamination events. The analysis also revealed that the widely used contamination data construction approach is misleading. PMID- 26905802 TI - Definition of an 18-mer Synthetic Peptide Derived from the GB virus C E1 Protein as a New HIV-1 Entry Inhibitor. AB - BACKGROUND: A slower progression of AIDS and increased survival in GBV-C positive individuals, compared with GBV-C negative individuals has been demonstrated; while the loss of GBV-C viremia was closely associated with a rise in mortality and increased progression of AIDS. Following on from the previous reported studies that support the thesis that GBV-C E2 interferes with HIV-1 entry, in this work we try to determine the role of the GBV-C E1 protein in HIV-1 inhibition. METHODS: The present work involves the construction of several overlapping peptide libraries scanning the GBV-C E1 protein and the evaluation of their anti-HIV activity. RESULTS: Specifically, an 18-mer synthetic peptide from the GBV-C E1 protein, E1(139-156), showed similar antiviral activity against HIVs from viruses from clades A, B, C, D and AE. Competitive ELISA using specific gp41 targeting mAbs, fluorescence resonance energy transfer as well as haemolysis assays demonstrated that this E1 peptide sequence interacts with the highly conserved N-terminal region of the HIV-1 gp41 (the fusion peptide) which is essential for viral entry. CONCLUSIONS: We have defined a novel peptide lead compound and described the inhibitory role of a highly conserved fragment of the E1 protein. GENERAL SIGNIFICANCE: The results together allow us to consider the non-pathogenic E1 GBV-C protein as an attractive source of peptides for the development of novel anti-HIV therapies. PMID- 26905803 TI - Chemical Constituents and Their Bioactivities of Mushroom Phellinus rhabarbarinus. AB - Phellinus rhabarbarinus soaked in wine has folk usages by local residents of Ailao mountain of Yunnan province, China, which were to daub the wound to prevent infection and to drink to enhance immunity and treat other diseases such as cough, gastritis, and cancer. Systemic investigation on the chemical constituents of fruiting bodies of P. rhabarbarinus resulted in the isolation of 11 lanostane triterpenoids (1-10) including three new ones, namely, phellibarins A-C (1-3), together with five ergosterols (11-15). This is the first time reporting secondary metabolites of P. rhabarbarinus. Compounds 2, 3, 7, and 8 showed inhibitory activities against nitric oxide (NO) production in LPS-activated RAW264.7 macrophages, whereas compounds 2-4, 6, 7, and 10 exhibited cytotoxicities against human cancer cell lines. The results of this assessment suggested that the lanostane triterpenoids in fruiting bodies of P. rhabarbarinus played key roles in its folk usages. PMID- 26905804 TI - A bispecific antibody effectively neutralizes all four serotypes of dengue virus by simultaneous blocking virus attachment and fusion. AB - Although dengue virus (DENV) infection severely threatens the health of humans, no specific antiviral drugs are currently approved for clinical use against DENV infection. Attachment and fusion are 2 critical steps for the flavivirus infection, and the corresponding functional epitopes are located at E protein domain III (E-DIII) and domain II (E-DII), respectively. Here, we constructed a bispecific antibody (DVD-1A1D-2A10) based on the 2 well-characterized anti-DENV monoclonal antibodies 1A1D-2 (1A1D) and 2A10G6 (2A10). The 1A1D antibody binds E DIII and can block the virus attaching to the cell surface, while the 2A10 antibody binds E-DII and is able to prevent the virus from fusing with the endosomal membrane. Our data showed that DVD-1A1D-2A10 retained the antigen binding activity of both parental antibodies. Importantly, it was demonstrated to be significantly more effective at neutralizing DENV than its parental antibodies both in vitro and in vivo, even better than the combination of them. To eliminate the potential antibody-dependent enhancement (ADE) effect, this bispecific antibody was successfully engineered to prevent Fc-gamma-R interaction. Overall, we generated a bispecific anti-DENV antibody targeting both attachment and fusion stages, and this bispecific antibody broadly neutralized all 4 serotypes of DENV without risk of ADE, suggesting that it has great potential as a novel antiviral strategy against DENV. PMID- 26905805 TI - Abnormal Injury Response in Spontaneous Mild Ventriculomegaly Wistar Rat Brains: A Pathological Correlation Study of Diffusion Tensor and Magnetization Transfer Imaging in Mild Traumatic Brain Injury. AB - Spontaneous mild ventriculomegaly (MVM) was previously reported in ~43% of Wistar rats in association with vascular anomalies without phenotypic manifestation. This mild traumatic brain injury (TBI) weight drop model study investigates whether MVM rats (n = 15) have different injury responses that could inadvertently complicate the interpretation of imaging studies compared with normal rats (n = 15). Quantitative MRI, including diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI), and immunohistochemistry (IHC) analysis were used to examine the injury pattern up to 8 days post-injury in MVM and normal rats. Prior to injury, the MVM brain showed significant higher mean diffusivity, axial diffusivity, and radial diffusivity, and lower fractional anisotropy (FA) and magnetization transfer ratio (MTR) in the corpus callosum than normal brain (p < 0.05). Following TBI, normal brains exhibited significant decreases of FA in the corpus callosum, whereas MVM brains demonstrated insignificant changes in FA, suggesting less axonal injury. At day 8 after mild TBI, MTR of the normal brains significantly decreased whereas the MTR of the MVM brains significantly increased. IHC staining substantiated the MRI findings, demonstrating limited axonal injury with significant increase of microgliosis and astrogliosis in MVM brain compared with normal animals. The radiological pathological correlation data showed that both DTI and MTI were sensitive in detecting mild diffuse brain injury, although DTI metrics were more specific in correlating with histologically identified pathologies. Compared with the higher correlation levels reflecting axonal injury pathology in the normal rat mild TBI, the DTI and MTR metrics were more affected by the increased inflammation in the MVM rat mild TBI. Because MVM Wistar rats appear normal, there was a need to screen rats prior to TBI research to rule out the presence of ventriculomegaly, which may complicate the interpretation of imaging and IHC observations. PMID- 26905806 TI - Urinary obstruction is an important complicating factor in patients with septic shock due to urinary infection. AB - OBJECTIVE: Urinary tract infection (UTI) is a common cause of severe sepsis, and anatomic urologic obstruction is a recognized factor for complicated disease. We aimed to identify the incidence of urinary obstruction complicating acute septic shock and determine the characteristics and outcomes of this group. METHODS: Patients prospectively enrolled in a sepsis treatment pathway registry between October 2013 and July 2014 were reviewed for the diagnosis of UTI. Standardized medical record review was performed to confirm sepsis due to UTI and determine clinical variables including the presence of anatomic urinary obstruction. Patients with septic shock due to UTI with obstruction were compared with those without obstruction. The primary outcomes were incidence of urinary obstruction and hospital mortality. RESULTS: Among 1084 registry enrollees, 209 (19.2%) met inclusion criteria for the study. Acute anatomic obstruction was identified in 22 (10.5%) patients. Hospital mortality in patients with obstruction was 27.3% compared with 11.2% in patients without obstruction (absolute difference of 16.1%; P = .03; 95% confidence interval [CI], 1.2%-30.9%). Hospital length of stay among survivors was 12.8 days compared with 8.3 days (absolute difference of 4.5 days; P = .04; 95% CI, 0.2-8.8 days). History of urinary stone disease was independently associated with obstruction (odds ratio, 5.6; 95% CI, 2.2-14.3). CONCLUSIONS: Approximately 1 in 10 patients presenting with septic shock due to a urinary source is complicated by anatomic urinary obstruction. These patients have significantly higher mortality compared with patients without obstruction. Early imaging of patients with septic shock due to suspected urinary source should be considered to identify obstruction requiring emergency intervention. PMID- 26905807 TI - Anatomic variations of sternum may mimic traumatic complications. PMID- 26905810 TI - Tacrolimus restores podocyte injury and stabilizes the expression of Cabin1 in 5/6 nephrectomized rats. AB - Podocyte injury is a vital factor, which induces massive proteinuria. Studies have shown that tacrolimus (TAC) protected podocyte via stabilizing cytoskeleton. Our latest study indicates that calcineurin binding protein 1 (Cabin1) undergoes nuclear translocation during podocytes injury. Whether TAC targets on Cabin1 during podocyte injury is still not clear. This study establishes non immunological proteinuric model. To observe the effect of the treatment of TAC on Cabin1 expression in 5/6 nephrectomized rats. Sprague-Dawley rats were injected with TAC (0.2 mg/kg/day) for 4-8 weeks after 5/6 nephrectomy. Then, rats were sacrificed in the eighth week after operation, renal tissues were processed for morphological studies under light and electrical microscope. Cabin1 expression and distribution were detected by western blot and indirect immunofluorescence staining. In 5/6 nephrectomized rats, urinary protein excretion reached 90.2 +/- 30.1 mg/24 h, glomerular sclerosis index and tubulointerstitial fibrosis score were significantly increased, and widespread of podocyte foot processes fusion was found. Moreover, Cabin1 protein expression was markedly increased, and its distribution became much more obviously in podocytes nuclei. In TAC treated rats, urinary protein excretion significantly decreased (44.9 +/- 22.5 mg/24 h), glomerular sclerosis and tubulointerstitial fibrosis were alleviated, and podocyte foot processes fusion was inhibited. Furthermore, TAC alleviated the increased protein expression and abnormal distribution of Cabin1. In conclusion, TAC restores podocyte injury and stabilizes the expression of Cabin1. Cabin1 may become a new target to demonstrate the mechanism of TAC in podocyte injury. PMID- 26905811 TI - Constant pH Molecular Dynamics Reveals pH-Modulated Binding of Two Small-Molecule BACE1 Inhibitors. AB - Targeting beta-secretase (BACE1) with small-molecule inhibitors offers a promising route for treatment of Alzheimer's disease. However, the intricate pH dependence of BACE1 function and inhibitor efficacy has posed major challenges for structure-based drug design. Here we investigate two structurally similar BACE1 inhibitors that have dramatically different inhibitory activity using continuous constant pH molecular dynamics (CpHMD). At high pH, both inhibitors are stably bound to BACE1; however, within the enzyme active pH range, only the iminopyrimidinone-based inhibitor remains bound, while the aminothiazine-based inhibitor becomes partially dissociated following the loss of hydrogen bonding with the active site and change of the 10s loop conformation. The drastically lower activity of the second inhibitor is due to the protonation of a catalytic aspartate and the lack of a propyne tail. This work demonstrates that CpHMD can be used for screening pH-dependent binding profiles of small-molecule inhibitors, providing a new tool for structure-based drug design and optimization. PMID- 26905812 TI - The fusion protein SS18-SSX1 employs core Wnt pathway transcription factors to induce a partial Wnt signature in synovial sarcoma. AB - Expression of the SS18/SYT-SSX fusion protein is believed to underlie the pathogenesis of synovial sarcoma (SS). Recent evidence suggests that deregulation of the Wnt pathway may play an important role in SS but the mechanisms whereby SS18-SSX might affect Wnt signaling remain to be elucidated. Here, we show that SS18/SSX tightly regulates the elevated expression of the key Wnt target AXIN2 in primary SS. SS18-SSX is shown to interact with TCF/LEF, TLE and HDAC but not beta catenin in vivo and to induce Wnt target gene expression by forming a complex containing promoter-bound TCF/LEF and HDAC but lacking beta-catenin. Our observations provide a tumor-specific mechanistic basis for Wnt target gene induction in SS that can occur in the absence of Wnt ligand stimulation. PMID- 26905813 TI - Gender-specific associations of genetic variants with metabolic syndrome components in the Tunisian population. AB - AIM OF THE STUDY: Recent genome-wide association studies (GWASs) have identified many genetic variants associated with metabolic syndrome (MetS). However, their contribution to MetS in ethnic groups in Tunisia is largely unexplored. In this study, we aim to examine the associations of related loci with a risk of metabolic syndrome in a sample of Tunisians. MATERIALS AND METHODS: Overall seven polymorphisms rs7265718, rs10401969, rs762861, rs12310367, rs1562398, rs2059807, rs4420638 located at C20orf152, CILP2, LRPAP1, ZNF664, KLF14, INSR, APOE, respectively, were analyzed in 356 samples from the Tunisian population. Anthropometric and biochemical parameters were assessed. Metabolic syndrome was defined according to the International Diabetes Federation (IDF). RESULTS: We find that LRPAP1-rs762861 C allele increases susceptibility to MetS (OR = 1.39, 95% CI = 0.99-1.95, p = 0.041). Separate analysis in men and women revealed the association of rs762861 among females (OR = 1.6, 95% CI = 1.057-2.41, p = 0.021), but not among males (OR = 0.953, 95% CI = 0.51-1.78, p = 0.882). ZNF664 rs12310367 was also found to be associated with body mass index (BMI) in women (p = 0.01) and not in men (p = 0.18). KLF14-rs1562398 was significantly correlated with impaired fasting glucose (p = 0.004) only in men. CONCLUSIONS: Our results reveal new candidate genes for MetS in the Tunisian population and suggest that the genetic basis of this syndrome is gender dependent. Further studies are necessary to understand why these associations differ between males and females. PMID- 26905814 TI - Quadrupole sensitive pulse for signal filtering. AB - A longstanding problem in quadrupolar NMR of semi-solids is the selection of signals originating from ordered nuclei, i.e. those that experience a non vanishing quadrupolar coupling. Established techniques, such as for example multiple-quantum filters are not adequate in situations when the radio frequency power is on the order of the quadrupolar coupling or the quadrupolar relaxation rates, such as may be the case on an MRI scanner, or in ex situ applications. In this manuscript we show a new method for the selective excitation of ordered spin 3/2 nuclei, which produces the desired results when the radio frequency power is approximately equal or smaller than quadrupolar frequency. Using a combination of simulations and experiments with (23)Na in NaCl solution, Pf1-solutions, and bovine patellar cartilage samples we further show how the value of the quadrupolar frequency and global features of a quadrupolar coupling distribution can be extracted from these experiments. PMID- 26905815 TI - The robust identification of exchange from T2-T2 time-domain features. AB - Two-dimensional spin-spin relaxation (T2-T2) techniques have been developed to probe coupling between different environments such as diffusive coupling between small and large pores or chemical exchange with clays. In these studies, Numerical Laplace Inversion (NLI) is used to obtain two-dimensional T2-T2 relaxation distribution spectrum from the T2-T2 signal decays, and the off diagonal peaks characterize coupling. Often, these coupling peaks are both weak and close to the diagonal and combined with the inherently ill-conditioned nature of the inversion, their presence is difficult to differentiate from inversion related artifacts and blurring. This manuscript presents a time domain based analysis to identify the presence of coupling that avoids the ambiguities present in T2-T2 spectra. The approach utilizes the symmetric nature of the two dimensional time domain data, where the presence of curvature along one of these symmetries gives an unambiguous indicator of coupling. Measurements on porous glass beads are used to verify the technique. PMID- 26905817 TI - Doxorubicin hydrochloric increases tumour coagulation and end-point survival in percutaneous microwave ablation of tumours in a VX2 rabbit tumour model. AB - PURPOSE: The aim of this study was to explore whether doxorubicin hydrochloric (DOX) combined with microwave ablation (MWA) is more effective at increasing tumour coagulation and prolonging end-point survival in a VX2 rabbit breast cancer model than each intervention individually. METHODS: New Zealand white rabbits with VX2 tumours were placed into treatment groups as follows: MWA (20 W for 5 min and 40 W for 5 min), intravenous injection of 4 mg/kg DOX, and combined therapy. Tumours were analysed at 4 h and 24 h after treatment to determine the temporal quantities of cleaved caspase-3 and Hsp70 using immunohistochemical staining and Western blots. Tumour coagulation areas were compared at 24 h after treatment. RESULTS: No significant difference in tumour coagulation was found between DOX-MWA and 40W-MWA (mean 4.52 cm(2) +/- 0.48 (SD), 4.08 cm(2) +/- 0.36, respectively; P > 0.05). A significant difference between tumour coagulation was found for DOX-MWA and 20W-MWA (mean 4.52 cm(2) +/- 0.48 (SD), 1.69 cm(2) +/- 0.34 cm(2), respectively; p < 0.01). Cleaved caspase-3 and Hsp70 demonstrated low level expression at 4 h and 24 h in the DOX group. Cleaved caspase-3 showed low expression at the coagulation margin in the 20W-MWA group, was highly expressed in DOX-MWA group, and continued to increase with time. Hsp70 in the 20W-MWA group increased significantly at the coagulation margin but demonstrated low expression in the DOX-MWA group at 4 h and 24 h. The animals in the combined treatment group had a longer survival time (mean 78.33 days +/- 8.07 SD) than the 20W-MWA group (mean 57.17 days +/- 8.77, p < 0.01) or the DOX group (mean 35.17 days +/- 7.63, p < 0.01). CONCLUSION: A combination of DOX and MWA could increase tumour coagulation and end-point survival better than single therapy, which had some connection with the elevated expression of cleaved caspase-3 and low Hsp70 expression at the coagulation margin. PMID- 26905816 TI - An efficient method and device for transfer of semisolid materials into solid state NMR spectroscopy rotors. AB - The study of mass-limited biological samples by magic angle spinning (MAS) solid state NMR spectroscopy critically relies upon the high-yield transfer of material from a biological preparation into the MAS rotor. This issue is particularly important for maintaining biological activity and hydration of semi-solid samples such as membrane proteins in lipid bilayers, pharmaceutical formulations, microcrystalline proteins and protein fibrils. Here we present protocols and designs for rotor-packing devices specifically suited for packing hydrated samples into Pencil-style 1.6 mm, 3.2 mm standard, and 3.2 mm limited speed MAS rotors. The devices are modular and therefore readily adaptable to other rotor and/or ultracentrifugation tube geometries. PMID- 26905818 TI - Observation of Zeeman effect in topological surface state with distinct material dependence. AB - Manipulating the spins of the topological surface states represents an essential step towards exploring the exotic quantum states emerging from the time reversal symmetry breaking via magnetic doping or external magnetic fields. The latter case relies on the Zeeman effect and thereby we need to estimate the g-factor of the topological surface state precisely. Here, we report the direct observations of the Zeeman effect at the surfaces of Bi2Se3 and Sb2Te2Se by spectroscopic imaging scanning tunnelling microscopy. The Zeeman shift of the zero mode Landau level is identified unambiguously by appropriately excluding the extrinsic effects arising from the nonlinearity in the band dispersion of the topological surface state and the spatially varying potential. Surprisingly, the g-factors of the topological surface states in Bi2Se3 and Sb2Te2Se are very different (+18 and -6, respectively). Such remarkable material dependence opens up a new route to control the spins of the topological surface states. PMID- 26905819 TI - Shared decision making in mental health: Myths, barriers, and benefits. PMID- 26905820 TI - Ulnar length as an alternative to height in the management of osteoporosis. PMID- 26905821 TI - Lack of Evidence for Nonotosclerotic Stapes Fixation in Human Temporal Bone Histopathology. AB - HYPOTHESIS: Nonotosclerotic stapes fixation does not represent a significant cause of stapes ankylosis in patients undergoing stapedectomy; the vast majority have otosclerosis. BACKGROUND: Nonotosclerotic stapes fixation has been proposed as the diagnosis in 30 to 40% of patients undergoing stapedectomy (after excluding rare congenital, systemic, and syndromic causes of stapes fixation and tympanosclerosis). This finding was based on the histopathologic evaluation of total stapedectomy surgical specimens. Since these specimens do not include the surrounding otic capsule, the histopathologic evidence of otosclerosis may be missed. METHODS: Human temporal bone specimens from patients who underwent stapes mobilization, stapedotomy, or stapedectomy during life were evaluated for histologic evidence of otosclerosis. Patients with a history of temporal bone trauma, tympanosclerosis, and congenital, systemic, or syndromic causes of stapes fixation were excluded. Therefore, most temporal bone donors carried a clinical diagnosis of otosclerosis. RESULTS: Two hundred ten specimens from three temporal bone collections were independently evaluated. Otosclerosis was found on histology in 99% (207/210). Therefore, the incidence of nonotosclerotic stapes fixation was 1% (3/210). In two of the three patients who did not have otosclerosis, the contralateral temporal bone had otosclerosis on histopathologic evaluation. These patients may have had otosclerosis in the footplate only (which was removed at the time of surgery and not available for review). CONCLUSION: Nonotosclerotic stapes fixation is not likely a distinct pathologic classification from otosclerosis. Most patients diagnosed with nonotosclerotic stapes fixation likely have otosclerosis, but do not have otosclerotic foci in the stapes itself. PMID- 26905822 TI - Molecular Impairment Mechanisms of Novel OPA1 Mutations Predicted by Molecular Modeling in Patients With Autosomal Dominant Optic Atrophy and Auditory Neuropathy Spectrum Disorder. AB - HYPOTHESIS: Different missense mutations of the optic atrophy 1 gene (OPA1) identified in optic atrophy patients with auditory neuropathy spectrum disorder (ANSD) induce functional impairment through different molecular mechanisms. BACKGROUND: OPA1 is the gene responsible for autosomal dominant optic atrophy (ADOA), but some of its mutations are also associated with ANSD. OPA1 is a member of the GTPase family of proteins and plays a key role in the maintenance of mitochondrial activities that are dependent on dimer formation of the protein. There are many reports of OPA1 mutations, but the molecular mechanisms of their functional impairments are unclear. METHODS: The sequences of coding regions in OPA1 were analyzed from blood samples of ADOA patients with ANSD. Molecular modeling of the protein's ability to form dimers and its GTP-binding ability were conducted to study the effects of structural changes in OPA1 caused by two identified mutations and their resultant effects on protein function. RESULTS: Two heterozygous mutations, p.T414P (c.1240A>C) and p.T540P (c.1618A>C), located in the GTPase and middle domains of OPA1, respectively, were identified in two patients. Molecular modeling indicated decreased dimer formation caused by destabilization of the association structure of the p.T414P mutant, and decreased GTP-binding caused by destabilization of the binding site structure in the p.T540P mutant. CONCLUSION: These two different conformational changes might result in decreased GTPase activities that trigger ADOA associated with ANSD, and are likely to be associated with mild clinical features. Molecular modeling would provide useful information in clinical practice. PMID- 26905823 TI - Diffusion Tensor Imaging Tractography of the Facial Nerve in Patients With Cerebellopontine Angle Tumors. AB - OBJECTIVE: To demonstrate the utility of diffusion tensor imaging (DTI) fiber tractography of the facial nerve in patients with cerebellopontine angle (CPA) tumors. STUDY DESIGN: Prospective. SETTING: Tertiary referral center. PATIENTS: DTI technique was established in 113 patients without tumors and in 28 patients with CPA tumors. Subsequently, DTI results were compared with intraoperative findings in 21 patients with medium and large-sized tumors, treated surgically via a translabyrinthine approach. INTERVENTION: Three Tesla magnetic resonance (MR) was used for DTI tractography. For patients without CPA tumors, the scanning protocol was 32 directions with a 3 * 3 * 3 mm voxel size. For CPA tumor patients, scanning protocol was 32 directions with a 2 * 2 * 2 mm voxel size. DTI data were used to track the facial nerve. MAIN OUTCOME MEASURES: Facial nerve identification rate. RESULTS: Facial nerve identification rate in MR-DTI was 97% and 100% in patients without tumors and in patients with tumors of the CPA of the internal auditory canal that were not treated surgically, respectively. MR-DTI identification of the facial nerve was successful in 20 patients who were treated surgically (95%). Good agreement between surgical findings and MR-DTI results was found in 19 patients (90%). CONCLUSION: MR DTI tractography is an effective technique in positively identifying the position of the facial nerve in patients with CPA tumors. PMID- 26905824 TI - Repeated Postoperative Follow-up Diffusion-weighted Magnetic Resonance Imaging to Detect Residual or Recurrent Cholesteatoma. AB - OBJECTIVE: In our institution, follow-up diffusion-weighted imaging (DWI) after cholesteatoma surgery is performed at least twice. The aim of this study was to determine the yield of the second follow-up DWI (D-W MRI-2) in patients in whom the first postoperative DWI (D-W MRI-1) was negative for residual or recurrent cholesteatoma. STUDY DESIGN: A retrospective analysis. SETTING: Tertiary referral center. PATIENTS: Patients were included if 1) they had at least two postoperative DWI examinations after a canal wall up procedure with apparently complete cholesteatoma resection; 2) D-W MRI-1 was performed between 6 and 24 months after surgery and D-W MRI-2 performed at least 6 months after D-W MRI-1; 3) both DWI examinations were of good quality and covering the whole mastoid middle ear region; 4) D-W MRI-1 was unequivocally negative for cholesteatoma; and 5) there was no clinical suspicion on otoscopy of recurrent cholesteatoma nor a surgical intervention between these two postoperative DWI examinations. In total, 45 separate ears in 44 patients were included. RESULTS: In 14 ears (31%) D-W MRI 2 was positive (n = 8) or equivocal (n = 6) for cholesteatoma. In six of eight patients with positive D-W MRI-2, follow-up surgery was performed. Cholesteatoma was found in five of them. None of the patients with equivocal findings on D-W MRI-2 was operated on. Patients with positive D-W MRI-2 were of young age. There were no observable differences for sex, side, time between surgery and D-W MRI-1, time between surgery and D-W MRI-2, or time between D-W MRI-1 and D-W MRI-2, or for the location of cholesteatoma at surgery. In the study period there was a trend to perform D-W MRI-1 and D-W MRI-2 earlier after initial surgery. In the same period, there was an evident decrease in average age of the patient population. CONCLUSION: Despite cholesteatoma surgery without macroscopic residue, clinical follow-up and routine first follow-up DWI without any signs of residual or recurrent disease, repeat follow-up DWI showed evidence of cholesteatoma in 31% of patients. On the basis of the findings in this study, repeated follow-up DWI is recommended. PMID- 26905825 TI - Postmortem diagnosis of Marfan syndrome in a case of sudden death due to aortic rupture: Detection of a novel FBN1 frameshift mutation. AB - To investigate the sudden death of a 36-year-old Chinese man, a medicolegal autopsy was performed, combining forensic pathological examinations and genetic sequencing analysis to diagnose the cause of death. Genomic DNA samples were extracted from blood and subjected to high-throughput sequencing. Major findings included a dilated aortic root with a ruptured and dissected aorta and consequent tamponade of the pericardial sac. Moreover, arachnodactyly and other skeletal deformities were noted. By sequencing the fibrillin-1 gene (FBN1), five genetic variations were found, including four previously known single nucleotide polymorphisms (SNPs) and a novel frameshift mutation, leading to the diagnosis of Marfan syndrome. The frameshift mutation (c.4921delG, p.glu1641llysFsX9) detected in exon 40 led to a stop codon after the next 8 amino acids. The four SNPs included a splice site mutation (c.3464-5 G>A, rs11853943), a synonymous mutation (p.Asn625Asn, rs25458), and two missense mutations (p.Pro1148Ala, rs140598; p.Cys472Tyr, rs4775765). Genetic screening was recommended for the relatives as it was reported that the father and brother of the deceased had died at the ages of 40 and 25, respectively, from sudden cardiac failure. The son of the deceased lacked the relevant mutations. This report emphasizes the important contribution of medicolegal postmortem analysis on the molecular pathogenesis study of Marfan syndrome and early diagnosis of at-risk relatives. PMID- 26905826 TI - Methylbenzene-Containing Polyketides from a Streptomyces that Spontaneously Acquired Rifampicin Resistance: Structural Elucidation and Biosynthesis. AB - Conventional screening for novel bioactive compounds in actinomycetes often results in the rediscovery of known compounds. In contrast, recent genome sequencing revealed that most of the predicted gene clusters for secondary metabolisms are not expressed under standard cultivation conditions. To explore the potential metabolites produced by these gene clusters, we implemented a cryptic gene activation strategy by screening mutants that acquire resistance to rifampicin. The induction of rifampicin resistance in 11 actinomycete strains generated 164 rifampicin-resistant mutants (rif mutants). The comparison of the metabolic profiles between the rif mutants and their wild-type strains indicated that one mutant (TW-R50-13) overproduced an unidentified metabolite (1). During the isolation and structural elucidation of metabolite 1, an additional metabolite was found; both are unprecedented compounds featuring a C5N unit and a methylbenzene moiety. Of these partial structures, the biosynthesis of the latter has not been reported. A feeding experiment using (13)C-labeled precursors demonstrated that the methylbenzene moiety is most likely synthesized by the action of polyketide synthase. The gene deletion experiments revealed that the genes for the methylbenzene moiety are located at a different locus than the genes for the C5N unit. PMID- 26905828 TI - Physiology of Ca(2+) signalling in stem cells of different origins and differentiation stages. AB - Stem cells (SCs) of different origins have brought hope as potential tools for the treatment of neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, and Amyotrophic Lateral Sclerosis. Calcium signalling plays a key role in SC differentiation and proliferation, and dysregulation of Ca(2+) homeostasis may instigate pathological scenarios. Currently, the role of ion channels and receptors in SCs is not fully understood. In the recent years, we found that (i) the pre-differentiation of human embryonic SCs (hESCs) led to the activation of Ca(2+) signalling cascades and enhanced the functional activities of these cells, (ii) the Ca(2+) homeostasis and the physiological properties of hESC-derived neural precursors (NPs) changed during long term propagation in vitro, (iii) differentiation of NPs derived from human induced pluripotent SCs affects the expression of ion channels and receptors, (iv) these neuronal precursors exhibited spontaneous activity, indicating that their electrophysiological and Ca(2+) handling properties are similar to those of mature neurones, and (v) in mesenchymal SCs isolated from the adipose tissue and bone marrow of rats the expression profile of ion channels and receptors depends not only on the differentiation conditions but also on the source from which the cells were isolated, indicating that the fate and functional properties of the differentiated cells are driven by intrinsic mechanisms. Together, identification and assignment of a unique ion channel and a Ca(2+) handling footprint for each cell type would be necessary to qualify them as physiologically suitable for medical research, drug screening, and cell therapy. PMID- 26905829 TI - Synthesis and herbicidal evaluation of novel benzothiazole derivatives as potential inhibitors of D1 protease. AB - D1 protease is a C-terminal processing protease that has been predicted to be an ideal herbicidal target. Three novel series of benzothiazole derivatives were synthesized and evaluated for their herbicidal activities against Brassica napus (rape) and Echinochloa crusgalli (barnyard grass). The preliminary bioassay indicated that most of the synthesized compounds possess promising D1 protease inhibitory activities and considerable herbicidal activities. Molecular docking was performed to position representative compounds into the active site of D1 protease to determine a probable binding model. PMID- 26905827 TI - ROS-activated calcium signaling mechanisms regulating endothelial barrier function. AB - Increased vascular permeability is a common pathogenic feature in many inflammatory diseases. For example in acute lung injury (ALI) and its most severe form, the acute respiratory distress syndrome (ARDS), lung microvessel endothelia lose their junctional integrity resulting in leakiness of the endothelial barrier and accumulation of protein rich edema. Increased reactive oxygen species (ROS) generated by neutrophils (PMNs) and other inflammatory cells play an important role in increasing endothelial permeability. In essence, multiple inflammatory syndromes are caused by dysfunction and compromise of the barrier properties of the endothelium as a consequence of unregulated acute inflammatory response. This review focuses on the role of ROS signaling in controlling endothelial permeability with particular focus on ALI. We summarize below recent progress in defining signaling events leading to increased endothelial permeability and ALI. PMID- 26905830 TI - Identification of novel estrogen receptor (ER) agonists that have additional and complementary anti-cancer activities via ER-independent mechanism. AB - In this study, a series of bis(4-hydroxy)benzophenone oxime ether derivatives such as 12c, 12e and 12h were identified as novel estrogen receptor (ER) agonists that have additional and complementary anti-proliferative activities via ER independent mechanism in cancer cells. These compounds are expected to overcome the therapeutic limitation of existing ER agonists such as estradiol and tamoxifen, which have been known to induce the proliferation of cancer cells. PMID- 26905831 TI - Altered activity profile of a tertiary silanol analog of multi-targeting nuclear receptor modulator T0901317. AB - We report the design, synthesis, and physicochemical/biological evaluation of novel silanol derivative 6 (sila-T) as a silanol analog of multi-target nuclear receptor modulator T0901317 (5). Compound 6 showed intermediate hydrophobicity between the corresponding alcohol 13 and perfluoroalcohol 5. While 5 exhibited potent activities toward liver X receptor alpha and beta, farnesoid X receptor, pregnane X receptor (PXR) and retinoic acid receptor-related orphan receptor (ROR)gamma, silanol 6 exhibited activity only toward PXR and RORs. Incorporation of silanol instead of perfluoroalcohol is a promising option for developing novel target-selective, biologically active compounds. PMID- 26905834 TI - Macroscopic switches constructed through host-guest chemistry. AB - Molecular switch systems, having been extensively studied in the solution phase, have the ability to perform with good controllability and rapid-responsiveness, making them ideally suited for the design of molecular devices for drug delivery, and information or sensing functions. Inspired by a wide range of objects with visual changes, like Mimosa pudica towards external stimuli, in order to understand molecular switches well, they must be interfaced with the macroscopic world so that they can be directly realized by visual detectable changes even observed by the naked eye. This can be critical for fabricating intelligent microfluidics and laboratory-on-chip devices, that may have wide applications in the fields of biology and materials science. But to realize this objective, especially for fabricating macroscopic surface switches, unveiling host-guest weak interactions to achieve visual phenomena is still the greatest thrill. Thankfully, surface contact angles provide us with a wonderful method to further investigate the microscopic origin of the macroscopic changes. Therefore, interfacial modification becomes a paramount process. Macrocyclic compounds, encompassing an innovative concept to deal with reversible noncovalent interactions between macrocyclic hosts and suitable guests, are good candidates for surface functionalization. In this feature article, we discuss recent developments in macroscopic contact angle switches formed by different macrocyclic hosts and highlight the properties of these new functional surfaces and their potential applications. PMID- 26905832 TI - Molecular alterations in sporadic pancreatic neuroendocrine microadenomas. AB - BACKGROUND: Pancreatic neuroendocrine microadenomas (pNEMAs) are neuroendocrine tumors measuring <5 mm in diameter. They are considered the precursor of pancreatic neuroendocrine tumors (pNETs). The aim of this study was to investigate the immunohistochemical differences between pNEMA, pNET, and hyperplasia of pancreatic islet cells (HPIL) in patients with non-familial syndromes. METHODS: We evaluated 21 pNEMAs, 19 HPILs, and 21 non-functional pNETs (10 G1 and 11 G2 cases) in patients with non-familial syndromes. Immunohistochemistry for tumor-associated markers death domain-associated protein (DAXX), alpha thalassemia/mental retardation X-linked (ATRX), cytokeratin 19 (CK19), bcl-2, and CD99 was performed. RESULTS: DAXX was expressed in 95%, 71%, and 71% of HPIL, pNEMA, and pNET samples, respectively; the differences were not significant. ATRX expression in pNEMA and pNET was significantly lower than that in HPIL, whereas there was no significant difference between pNEMA and pNET (HPIL: 95%, pNEMA: 43%, and pNET: 52%). All HPIL and pNEMA cases were negative for bcl-2 and positive for CD99, whereas 29% of pNETs were positive for bcl-2 and 24% were negative for CD99. CK19 expression in HPIL was significantly lower than in pNEMA and pNET, although no significant difference was observed between pNEMA and pNET (HPIL: 5%, pNEMA: 57%, and pNET: 43%). Among G1 and G2 pNETs, CD99 was expressed in 50% of G1 pNETs but not in any G2 pNET cases. CONCLUSION: Non familial HPIL, pNEMA, and pNET patients exhibit distinct ATRX, CD99, CK19, and bcl-2 molecular profiles. PMID- 26905833 TI - Registered report: A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations. AB - The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of selected experiments from a substantial number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 2012, were selected on the basis of citations and Altmetric scores (Errington et al., 2014). This Registered Report describes the proposed replication plan of experiments from "A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations" by Sharma and colleagues, published in Cell in 2010 (Sharma et al., 2010). Sharma and colleagues demonstrated that prolonged exposure of cancer cells to TKIs give rise to small populations of "drug tolerant persisters" (DTPs) (Figure 1B-C) that were reversed during subsequent maintenance under drug free conditions (Figures 1E, 2B and 2E). DTPs exhibited reduced histone acetylation and sensitivity to HDAC inhibitors (HDIs) (Figure 4A-B). Drug sensitivity was restored with co-treatment of either HDIs or an IGF-1R inhibitor, in combination with TKIs (Figure 5A-B). Inhibition of IGF-1R activation also led to decreased KDM5A expression and restoration of H3K4 methylation, suggesting a direct link between the IGF-1R signaling pathway and KDM5A function (Figure 7A, 7C, and 7I). The Reproducibility Project: Cancer Biology is a collaboration between the Center for Open Science and Science Exchange and the results of the replications will be published in eLife. PMID- 26905835 TI - Seductive research narratives. PMID- 26905836 TI - [Re: An illogical and unfortunate side effect concept]. PMID- 26905837 TI - [L. Slordal & T. Christoffersen reply]. PMID- 26905838 TI - [Re: What causes febrile convulsions?]. PMID- 26905839 TI - [Antibiotic prophylaxis against infective endocarditis]. PMID- 26905840 TI - [The debate about emergency medicine in Norway]. PMID- 26905841 TI - [The cruciate ligament register--due for a change?]. PMID- 26905843 TI - [Distinguishing diagnostics from research]. PMID- 26905842 TI - [New tool to detect delirium and cognitive impairment]. PMID- 26905844 TI - [Not Available]. PMID- 26905845 TI - Peer counsellors' views on the collegial support scheme for doctors. AB - BACKGROUND: The health condition and health-related behaviour of doctors are important to the doctors themselves as well as for their treatment of patients. The collegial support scheme is a county-based and easily accessible health and care service for doctors. We therefore wanted to describe the framework and functions of this scheme and examine its utility. MATERIAL AND METHOD: Fourteen focus-group interviews with a total of 61 peer counsellors from all the counties were conducted. The interviews were recorded, transcribed and analysed with the aid of systematic text condensation. RESULTS: The framework--easy accessibility, a readily available offer of up to three sessions, a high degree of confidentiality and informal contact--was emphasised as crucial for doctors to make use of the scheme. The peer counsellors described their role as that of a listener and supportive helper. They helped bring clarity and discuss possible needs for further follow-up or treatment of numerous different and frequently complex issues. The peer counsellors highlighted three benefits in particular: the scheme helps raise awareness by legitimising help-seeking behaviour among doctors, it is a contingency scheme, and it eases the burden by lowering the threshold to seeking out further advice and treatment. INTERPRETATION: A systematic evaluation of the collegial support scheme is important for an understanding of the totality of the collegial health and care services. The collegial support scheme may lower the threshold to seeking help, and encourage some doctors to seek necessary treatment. PMID- 26905846 TI - [Use of antibiotics during pregnancy]. AB - BACKGROUND: Antibiotics are the most widely used medication on prescription in pregnancy. It is therefore important to investigate whether antibiotic use in pregnancy can harm the foetus. During the last decade the availability of data from national registries has made it possible to conduct large-scale epidemiological studies. In this article we aimed to review recent studies on the risk of congenital anomalies and miscarriage resulting from the use of antibiotics in pregnancy. METHOD: A literature search was conducted in MedLine, Embase and PubMed for the period 1 December 2005-1 December 2015. We identified 1,316 articles, of which 23 met the inclusion criteria. RESULTS: Recent epidemiological studies have focused on investigating the risks of malformations and pyloric stenosis after exposure to macrolides, nitrofurantoin, penicillins and trimethoprim-sulphamethoxazole. In nine of ten studies that included in total more than 38,000 patients exposed to macrolides, and two studies with more than 7,000 exposed to nitrofurantoin, no significantly increased risk of malformations was discovered. There are some contradictory findings for certain groups of antibiotics with regard to the risk of miscarriage, heart defects and pyloric stenosis. INTERPRETATION: Recent studies indicate that erythromycin and nitrofurantoin can be used as second-line drugs in the first trimester. The results from recent studies concur with the recommendations for pregnant women in national guidelines regarding antibiotic use in the primary health service. PMID- 26905847 TI - [Long-term adverse effects of anti-epileptic drugs]. AB - Around 120,000 patients in Norway use anti-epileptic drugs daily. Their use has increased in recent years, partly because these drugs are also used for psychiatric disorders, migraine and neuropathic pain. Treatment usually lasts for many years. It is important for doctors to familiarise themselves with the adverse effect profile of these drugs, especially because the long-term adverse effects are generally insidious and are easy for both doctor and patient to overlook. PMID- 26905848 TI - [A man in his 30s with fever after a safari in South Africa]. PMID- 26905849 TI - [Compassionate use of drugs]. PMID- 26905850 TI - [Not Available]. PMID- 26905852 TI - [Not Available]. PMID- 26905853 TI - [Not Available]. PMID- 26905854 TI - [Not Available]. PMID- 26905855 TI - [Not Available]. PMID- 26905856 TI - [Not Available]. PMID- 26905859 TI - Growing Carbon Nanotubes from Both Sides of Graphene. AB - The design and synthesis of hybrid structures between graphene and carbon nanotubes is an intriguing topic in the field of carbon nanomaterials. Here the synthesis of vertically aligned CNT carpets underneath graphene and from both sides of graphene is described with continuous ordering over a large area. Scanning electron microscopy and Raman spectroscopic characterizations show that CNT carpets grow underneath graphene through a base-growth mechanism, and grow on top of graphene through a tip-growth mechanism. Good electrical contact is observed from the top CNT carpets, through the graphene layer, to the bottom CNT carpets. This sandwich-like CNT/graphene/CNT hybrid structure could provide an approach to design and fabricate multilayered graphene/CNTs materials, as well as potential applications in the fields of nanomanufacturing and energy storage. PMID- 26905861 TI - Deaths: Final Data for 2013. AB - OBJECTIVES: This report presents final 2013 data on U.S. deaths, death rates, life expectancy, infant mortality, and trends, by selected characteristics such as age, sex, Hispanic origin, race, state of residence, and cause of death. METHODS: Information reported on death certificates, which are completed by funeral directors, attending physicians, medical examiners, and coroners, is presented in descriptive tabulations. The original records are filed in state registration offices. Statistical information is compiled in a national database through the Vital Statistics Cooperative Program of the Centers for Disease Control and Prevention's National Center for Health Statistics. Causes of death are processed in accordance with the International Classification of Diseases, Tenth Revision. RESULTS: In 2013, a total of 2,596,993 deaths were reported in the United States. The age-adjusted death rate was 731.9 deaths per 100,000 U.S. standard population, a record low figure, but the decrease in 2013 from 2012 was not statistically significant. Life expectancy at birth was 78.8 years, the same as in 2012. Age-specific death rates decreased in 2013 from 2012 for age groups 15-24 and 75-84. Age-specific death rates increased only for age group 55-64. The 15 leading causes of death in 2013 remained the same as in 2012, although Accidents (unintentional injuries), the 5th leading cause of death in 2012, became the 4th leading cause in 2013, while Cerebrovascular diseases (stroke), the 4th leading cause in 2012, became the 5th leading cause of death in 2013. The infant mortality rate of 5.96 deaths per 1,000 live births in 2013 was a historically low value, but it was not significantly different from the 2012 rate. CONCLUSIONS: Although statistically unchanged from 2012, the decline in the age-adjusted death rate is consistent with long-term trends in mortality. Life expectancy in 2013 remained the same as in 2012. PMID- 26905860 TI - The impact of inhibitory mechanisms in the inner retina on spatial tuning of RGCs. AB - Spatial tuning properties of retinal ganglion cells (RGCs) are sharpened by lateral inhibition originating at both the outer and inner plexiform layers. Lateral inhibition in the retina contributes to local contrast enhancement and sharpens edges. In this study, we used dynamic clamp recordings to examine the contribution of inner plexiform inhibition, originating from spiking amacrine cells, to the spatial tuning of RGCs. This was achieved by injecting currents generated from physiologically recorded excitatory and inhibitory stimulus-evoked conductances, into different types of primate and mouse RGCs. We determined the effects of injections of size-dependent conductances in which presynaptic inhibition and/or direct inhibition onto RGCs were partly removed by blocking the activity of spiking amacrine cells. We found that inhibition originating from spiking amacrine cells onto bipolar cell terminals and onto RGCs, work together to sharpen the spatial tuning of RGCs. Furthermore, direct inhibition is crucial for preventing spike generation at stimulus offset. These results reveal how inhibitory mechanisms in the inner plexiform layer contribute to determining size tuning and provide specificity to stimulus polarity. PMID- 26905862 TI - Analysis of the Maillard reaction in human hair using Fourier transform infrared spectroscopic imaging and a focal-plane array detector. AB - The Maillard reaction has been well researched and used in the food industry and the fields of environmental science and organic chemistry. Here, we induced the Maillard reaction inside human hair and analyzed its effects by using Fourier transform infrared spectroscopy with a focal-plane array (FTIR-FPA) detector. We used arginine (A), glycine (G), and D-xylose (X) to generate the Maillard reaction by dissolving them in purified water and heating it to 150 degrees C. This label-free process generated a complex compound (named AGX after its ingredients) with a monomer structure, which was determined by using nuclear magnetic resonance (NMR) and FTIR-FPA. This compound was stable in hair and substantially increased its tensile strength. To our knowledge, we are the first to report the formation of this monomer in human hair, and our study provides insights into a new method that could be used to improve the condition of damaged or aging hair. PMID- 26905863 TI - Sweet potato as an alternative to potato in gestational diabetes mellitus. PMID- 26905864 TI - A phase III, multicentre, randomised, double-blind, active-controlled, parallel group trial comparing safety and efficacy of HD203, with innovator etanercept, in combination with methotrexate, in patients with rheumatoid arthritis: the HERA study. AB - OBJECTIVES: To evaluate equivalence in efficacy for rheumatoid arthritis (RA) and compare the safety of the biosimilar HD203 with innovator etanercept (ETN) plus methotrexate (MTX) (ClinicalTrials.gov NCT01270997). METHODS: Patients with active RA received 25 mg HD203 or ETN subcutaneously twice-weekly with MTX for 48 weeks in a phase III, multicentre, randomised, double-blind, parallel-group design. The primary end point was the proportion of patients achieving the American College of Rheumatology 20% response (ACR20) at week 24 for per-protocol study completer set (PPS). Secondary end points included ACR response criteria, ACRn, European League against Rheumatism (EULAR) response, change in Disease Activity Score 28 (DAS28), patient-reported outcomes, safety and immunogenicity. RESULTS: Of the 294 randomised patients (HD203, n=147; ETN, n=147), 233 comprised the 24-week PPS (n=115 and 118, respectively). ACR20 at week 24 was achieved by 83.48% and 81.36% of PPS patients, respectively, demonstrating equivalent efficacy within predefined margins of +/-20% (treatment difference 2.12%, 95% CI 7.65% to 11.89%). Outcomes for secondary end points were consistent with the primary efficacy findings. Groups were comparable for overall incidences of treatment-emergent (all-causality) adverse events (AEs) (HD203 113 (76.9%) vs ETN 114 (78.1%) (p=0.804)), adverse drug reactions, serious AEs and discontinuations due to AEs. Few patients (HD203, n=8; ETN, n=3) tested positive for anti-drug antibodies. CONCLUSION: The study met the primary objective of demonstrating equivalent efficacy of HD203 and ETN. HD203 was well tolerated, with safety comparable with ETN in this population of patients with RA. TRIAL REGISTRATION NUMBER: NCT01270997; Results. PMID- 26905865 TI - Feasibility of 320-row area detector CT coronary angiography using 40 mL of contrast material: assessment of image quality and diagnostic accuracy. AB - OBJECTIVES: To assess the image quality and diagnostic accuracy of 320-row area detector CT (320-ADCT) coronary angiography using 40 mL of contrast material in comparison with 60-mL protocol. METHODS: This retrospective study included 183 patients who underwent 320-ADCT coronary angiography using 40 mL of contrast and additional 183 sex- and body mass index-matched patients using 60 mL of contrast constituting the control group. Both groups used the same 5-mL/sec injection rate. Quantitative image quality measurements and diagnostic accuracies were calculated and compared. RESULTS: Mean attenuation and contrast-to-noise ratio (CNR) at the aorta and all coronary arteries were lower in the 40-mL group than in the 60-mL group (all, p < 0.05), except for the CNR at proximal coronary arteries at 100 kVp (p = 0.073). However, the proportion of coronary segments with vessel attenuation >250 HU was not different between groups (all, p > 0.05), except for distal coronary arteries at 80 kVp (p = 0.001). Furthermore, there were no differences in per-patient and per-segment diagnostic accuracies between the groups (all, p > 0.05). CONCLUSIONS: 320-ADCT coronary angiography using 40 mL of contrast showed image quality and diagnostic accuracy comparable to the 60 mL protocol, demonstrating the clinical feasibility of lowering the risk of contrast-induced nephropathy through contrast volume reduction. KEY POINTS: * 320 ADCT might enable reduction of contrast material volume. * A 40-mL contrast protocol for 320-ADCT provided acceptable image quality. * A 40-mL contrast protocol for 320-ADCT demonstrated sufficient diagnostic accuracy. PMID- 26905866 TI - Added value of CT perfusion compared to CT angiography in predicting clinical outcomes of stroke patients treated with mechanical thrombectomy. AB - OBJECTIVES: CTP images analyzed with the Alberta stroke program early CT scale (ASPECTS) have been shown to be optimal predictors of clinical outcome. In this study we compared two biomarkers, the cerebral blood volume (CBV)-ASPECTS and the CTA-ASPECTS as predictors of clinical outcome after thrombectomy. METHODS: Stroke patients with thrombosis of the M1 segment of the middle cerebral artery were included in our study. All patients underwent initial multimodal CT with CTP and CTA on a modern CT scanner. Treatment consisted of full dose intravenous tissue plasminogen activator, when applicable, and mechanical thrombectomy. Three neuroradiologists separately scored CTP and CTA images with the ASPECTS score. RESULTS: Sixty-five patients were included. Median baseline CBV-ASPECTS and CTA ASPECTS for patients with favourable clinical outcome at follow-up were 8 [interquartile range (IQR) 8-9 and 7-9 respectively]. Patients with poor clinical outcome showed a median baseline CBV-ASPECTS of 6 (IQR 5-8, P < 0.0001) and a median baseline CTA-ASPECTS of 7 (IQR 7-8, P = 0.18). Using CBV-ASPECTS and CTA ASPECTS raters predicted futile reperfusions in 96 % and 56 % of the cases, respectively. CONCLUSIONS: CBV-ASPECTS is a significant predictor of clinical outcome in patients with acute ischemic stroke treated with mechanical thrombectomy. KEY POINTS: * CBV-ASPECTS is a significant predictor of clinical outcome. * Single phase CTA-ASPECTS has low predictive value. * Using CBV ASPECTS, raters identified futile reperfusions in 96 % of the cases. PMID- 26905867 TI - Time-resolved magnetic resonance angiography (MRA) at 3.0 Tesla for evaluation of hemodynamic characteristics of vascular malformations: description of distinct subgroups. AB - OBJECTIVES: Quantitative evaluation of hemodynamic characteristics of arteriovenous and venous malformations using time-resolved magnetic resonance angiography (MRA) at 3.0 Tesla. METHODS: Time-resolved MRA with interleaved stochastic trajectories (TWIST) at 3.0 Tesla was studied in 83 consecutive patients with venous malformations (VM) and arteriovenous malformations (AVM). Enhancement characteristics were calculated as percentage increase of signal intensity above baseline over time. Maximum percentage signal intensity increase (signalmax), time intervals between onset of arterial enhancement and lesion enhancement (tonset), and time intervals between beginning of lesion enhancement and maximum percentage of lesion enhancement (tmax) were analyzed. RESULTS: All AVMs showed a high-flow hemodynamic pattern. Two significantly different (p < 0.001) types of venous malformations emerged: VMs with arteriovenous fistulas (AVF) (median signalmax 737 %, IQR [interquartile range] = 511 - 1182 %; median tonset 5 s, IQR = 5 - 10 s; median tmax 35 s, IQR = 26 - 40 s) and without AVFs (median signalmax 284 %, IQR = 177-432 %; median tonset 23 s, IQR = 15 - 30 s; median tmax 60 s, IQR = 55 - 75 s). CONCLUSIONS: Quantitative evaluation of time resolved MRA at 3.0 Tesla provides hemodynamic characterization of vascular malformations. VMs can be subclassified into two hemodynamic subgroups due to presence or absence of AVFs. KEY POINTS: * Time-resolved MRA at 3.0 Tesla provides quantitative hemodynamic characterization of vascular malformations. * Malformations significantly differ in time courses of enhancement and signal intensity increase. * AVMs show a distinctive high-flow hemodynamic pattern. * Two significantly different types of VMs emerged: VMs with and without AVFs. PMID- 26905868 TI - Balloon pulmonary angioplasty: applicability of C-Arm CT for procedure guidance. AB - PURPOSE: To investigate the feasibility of and compare two C-Arm CT (CACT) guidance methods during balloon pulmonary angioplasty (BPA). MATERIAL AND METHODS: Forty-two BPAs [27 CTEPH patients (nine males, 70 +/- 14y)] targeting 143 pulmonary arteries were included. Twenty-two BPAs were guided by contrast enhanced CACT acquired immediately before BPA (G3D). In another 20 BPAs (G2D), two orthogonal fluoroscopy images of the chest where acquired to compute a registration of a previously acquired CACT. Volume rendering-based graphic representations (VRT guidance) were generated indicating the origin and course of the vessels. Based on VRT guidance, the intervention was planned. Procedure durations and radiation exposure data were compared between the two groups (Wilcoxon test). RESULTS: The overall intervention time was approximately 2 h in both groups (p = 0.31). BPA was successfully performed in G3D 91 % and G2D 94 %. No significant difference was found concerning the mean dose area product (DAP) related to fluoroscopy (p = 0.38), while DAP related to DSA was slightly higher in G3D (p = 0.048). Overall, DAP was significantly higher in G3D (p = 0.002). CONCLUSIONS: The use of CACT for procedure guidance in patients undergoing BPA is feasible and accurate. Image fusion of a pre-acquired CACT can be used to decrease radiation exposure due to multiple BPA sessions. KEY POINTS: * BPA guidance by CACT overlay is feasible and safe. * 2D3D image fusion for BPA guidance is accurate. * Image fusion can reduce patient radiation dose due to repeated BPA sessions. PMID- 26905869 TI - Simultaneous assessment of cerebral blood volume and diffusion heterogeneity using hybrid IVIM and DK MR imaging: initial experience with brain tumors. AB - OBJECTIVES: To investigate the feasibility of simultaneously assessing cerebral blood volume and diffusion heterogeneity using hybrid diffusion-kurtosis (DK) and intravoxel-incoherent-motion (IVIM) MR imaging. METHODS: Fifteen healthy volunteers and 30 patients with histologically proven brain tumours (25 WHO grade II-IV gliomas and five metastases) were recruited. On a 3-T system, diffusion weighted imaging was performed with six b-values ranging from 0 to 1,700 s/mm2. Nonlinear least-squares fitting was employed to extract diffusion coefficient (D), diffusion kurtosis coefficient (K, a measure of the degree of non-Gaussian and heterogeneous diffusion) and intravascular volume fraction (f, a measure proportional to cerebral blood volume). Repeated-measures multivariate analysis of variance and receiver operating characteristic analysis were performed to assess the ability of D/K/f in differentiating contrast-enhanced tumour from peritumoral oedema and normal-appearing white matter. RESULTS: Based on our imaging setting (baseline signal-to-noise ratio = 32-128), coefficient of variation was 14-20 % for K, ~6 % for D and 26-44 % for f. The indexes were able to differentiate contrast-enhanced tumour (Wilks' lambda = 0.026, p < 10-3), and performance was greatest with K, followed by f and D. CONCLUSIONS: Hybrid DK IVIM imaging is capable of simultaneously measuring cerebral perfusion and diffusion indexes that together may improve brain tumour diagnosis. KEY POINTS: * Hybrid DK IVIM imaging allows simultaneous measurement of K, D and f. * Combined K/D/f better demarcates contrast-enhanced tumour than they do separately. * f correlates better with contrast-leakage-corrected CBV DSC than with uncorrected CBV DSC. PMID- 26905870 TI - In vivo dentate nucleus MRI relaxometry correlates with previous administration of Gadolinium-based contrast agents. AB - OBJECTIVES: To evaluate changes in T1 and T2* relaxometry of dentate nuclei (DN) with respect to the number of previous administrations of Gadolinium-based contrast agents (GBCA). METHODS: In 74 relapsing-remitting multiple sclerosis (RR MS) patients with variable disease duration (9.8+/-6.8 years) and severity (Expanded Disability Status Scale scores:3.1+/-0.9), the DN R1 (1/T1) and R2* (1/T2*) relaxation rates were measured using two unenhanced 3D Dual-Echo spoiled Gradient-Echo sequences with different flip angles. Correlations of the number of previous GBCA administrations with DN R1 and R2* relaxation rates were tested, including gender and age effect, in a multivariate regression analysis. RESULTS: The DN R1 (normalized by brainstem) significantly correlated with the number of GBCA administrations (p<0.001), maintaining the same significance even when including MS-related factors. Instead, the DN R2* values correlated only with age (p=0.003), and not with GBCA administrations (p=0.67). In a subgroup of 35 patients for whom the administered GBCA subtype was known, the effect of GBCA on DN R1 appeared mainly related to linear GBCA. CONCLUSIONS: In RR-MS patients, the number of previous GBCA administrations correlates with R1 relaxation rates of DN, while R2* values remain unaffected, suggesting that T1-shortening in these patients is related to the amount of Gadolinium given. KEY POINTS: * In multiple sclerosis, previous Gadolinium administrations correlate with dentate nuclei T1 relaxometry. * Such correlation is linked to linear Gadolinium chelates and unrelated to disease duration or severity. * Dentate nuclei T2* relaxometry is age-related and independent of previous Gadolinium administrations. * Changes in dentate nuclei T1 relaxometry are not determined by iron accumulation. * MR relaxometry can quantitatively assess Gadolinium accumulation in dentate nuclei. PMID- 26905871 TI - Cost evaluation of gadoxetic acid-enhanced magnetic resonance imaging in the diagnosis of colorectal-cancer metastasis in the liver: Results from the VALUE Trial. AB - OBJECTIVES: To assess the costs of diagnostic workup and surgery of three strategies for patients with colorectal cancer liver-metastases (CRCLM): gadoxetic-acid-enhanced MRI (Gd-EOB-DTPA-MRI), MRI with extracellular contrast media (ECCM-MRI) or contrast-enhanced MDCT (CE-MDCT). METHODS: The within-trial cost evaluation was modelled as a decision-tree to calculate the cost of diagnosis and surgery. The model used clinical outcomes and resource utilization data from a prospective randomized multicentre study. Analyses were performed for the 354-patient safety population from eight participating countries. RESULTS: The diagnostic workup cost using Gd-EOB-DTPA-MRI upfront resulted in savings compared to ECCM-MRI in all countries except Thailand (difference <2 %). Compared to CE-MDCT, initial imaging with Gd-EOB-DTPA-MRI was less costly in all countries except Korea and Spain (differences 4 and 8 %, respectively). Significantly more patients in the Gd-EOB-DTPA-MRI group were eligible for surgery (39.3 % (48/122) vs. 31.0 % (36/116) and 26.7 % (31/116) for ECCM-MRI and CE-MDCT, respectively), allowing more patients to undergo potentially curative surgery, but resulting in higher treatment costs for the strategy starting with Gd-EOB-DTPA-MRI. CONCLUSIONS: The benefits of Gd-EOB-DTPA-MRI due to less additional imaging and similar diagnostic workup costs in the three groups suggest that Gd-EOB-DTPA-MRI should be the preferred initial imaging procedure to evaluate hepatic resectability in patients with CRCLM. KEY POINTS: * Diagnostic imaging cost to evaluate resectability was similar among the groups * Cost for imaging was rather small compared to the cost of surgery * Significantly more patients in the Gd-EOB DTPA-MRI arm were eligible for surgery * Gd-EOB-DTPA-MRI is recommended for evaluating hepatic resectability in patients with CRCLM. PMID- 26905872 TI - Cost-Effectiveness Analysis: Risk Stratification of Nonalcoholic Fatty Liver Disease (NAFLD) by the Primary Care Physician Using the NAFLD Fibrosis Score. AB - BACKGROUND: The complications of Nonalcoholic Fatty Liver Disease (NAFLD) are dependent on the presence of advanced fibrosis. Given the high prevalence of NAFLD in the US, the optimal evaluation of NAFLD likely involves triage by a primary care physician (PCP) with advanced disease managed by gastroenterologists. METHODS: We compared the cost-effectiveness of fibrosis risk assessment strategies in a cohort of 10,000 simulated American patients with NAFLD performed in either PCP or referral clinics using a decision analytical microsimulation state-transition model. The strategies included use of vibration controlled transient elastography (VCTE), the NAFLD fibrosis score (NFS), combination testing with NFS and VCTE, and liver biopsy (usual care by a specialist only). NFS and VCTE performance was obtained from a prospective cohort of 164 patients with NAFLD. Outcomes included cost per quality adjusted life year (QALY) and correct classification of fibrosis. RESULTS: Risk-stratification by the PCP using the NFS alone costs $5,985 per QALY while usual care costs $7,229/QALY. In the microsimulation, at a willingness-to-pay threshold of $100,000, the NFS alone in PCP clinic was the most cost-effective strategy in 94.2% of samples, followed by combination NFS/VCTE in the PCP clinic (5.6%) and usual care in 0.2%. The NFS based strategies yield the best biopsy-correct classification ratios (3.5) while the NFS/VCTE and usual care strategies yield more correct-classifications of advanced fibrosis at the cost of 3 and 37 additional biopsies per classification. CONCLUSION: Risk-stratification of patients with NAFLD primary care clinic is a cost-effective strategy that should be formally explored in clinical practice. PMID- 26905873 TI - Anaesthesia and global health initiatives for children in a low-resource environment. AB - PURPOSE OF REVIEW: As the United Nations moves from Millennium Development Goals to Sustainable Development Goals, we find ourselves with the opportunity to influence the priority of global health initiatives. Previously, the global health community has failed to recognise the importance of access to safe, affordable surgery and developing the necessary specialities that support it as most of the funding focus had been on primary healthcare and infectious diseases. RECENT FINDINGS: Now the WHO is publishing guidelines to safe surgery and the Lancet Commission on Global Surgery has been launched. However, this is only the start; anaesthesia remains a forgotten speciality within the world of public and global health and there are still challenges in escalating surgery in low and middle-income countries to an acceptable level that is affordable and timely. SUMMARY: Although there is increased world interest in safe surgery and anaesthesia this has not yet been translated into a mandate that will compel countries to invest in improving levels of infrastructure, accessibility, manpower, and safety. A general anaesthetic remains a dangerous event in a child's life in resource-limited countries. PMID- 26905874 TI - Patients prone for postoperative delirium: preoperative assessment, perioperative prophylaxis, postoperative treatment. AB - PURPOSE OF REVIEW: The aim of this study was to review current literature on identification of patients at risk for postoperative delirium (POD) and to summarize recent findings on prophylaxis and treatment. RECENT FINDINGS: Age and preoperative cognitive impairment are among the most important risk factors of POD. POD is the result of a complex interplay of predisposing and precipitating factors. Thus, both prophylaxis and treatment require multicomponent intervention programs. No single medication to prevent or treat POD is available. Avoiding too deep anesthesia, avoiding additional psychoactive substances including benzodiazepines and intravenous opioids, and effective pain management as well as early mobilization are essential. SUMMARY: An increase of the proportion of elderly patients undergoing surgery will lead to a higher incidence of POD. Preoperative assessment should facilitate identification of patients at high risk. Perioperative management should include monitoring depth of anesthesia, preference for nonopioid pain therapy, early regular delirium monitoring starting in the recovery room, avoiding ICU-sedation, early mobilization and exercise, and cognitive training. PMID- 26905875 TI - Prostate cancer arising in ectopic prostatic tissue within the left seminal vesicle: a rare case diagnosed with multi-parametric magnetic resonance imaging and magnetic resonance imaging-transrectal ultrasound fusion biopsy. AB - BACKGROUND: Benign ectopia of prostatic glandular tissue in the seminal vesicles is rare with only three prior cases reported in the literature. Prostate cancer, arising within prostatic ectopia in the seminal vesicles, has never been described and therefore presents a challenge in both diagnosis and management. CASE PRESENTATION: Herein, we report a rare case of prostatic adenocarcinoma in ectopic prostate tissue in the left seminal vesicle, without evidence of prostatic glandular involvement. This case was diagnosed on multi-parametric magnetic resonance imaging and confirmed with magnetic resonance imaging transrectal ultrasound fusion biopsy. CONCLUSIONS: Awareness of this unusual phenomenon is significant because of the potential occurrence of malignancy to arise in unexpected, extra-glandular locations, which are not routinely sampled on routine transrectal ultrasound biopsy. However attention to lesions with characteristic multi-parametric magnetic resonance imaging features of prostate cancer, regardless of extra-glandular location, will help direct tissue sampling, facilitate a timely diagnosis and ensure appropriate management. PMID- 26905876 TI - [Not Available]. PMID- 26905877 TI - Mechanism of nonylphenol-induced neurotoxicity in F1 rats during sexual maturity. AB - OBJECTIVE: The purpose of this study was to examine whether gestational and lactational exposure to environmental endocrine disrupting chemical, nonylphenol (NP), in pregnant dams would lead to the alterations in hormone levels in the body, apoptosis and glial fibrillary acidic protein (GFAP) in hippocampus during weaning and sexual maturity periods in pups of rats. METHODS: Dams were gavaged with NP at dose levels of 25 mg/kg/day (low dose), 50 mg/kg/day (middle dose), 100 mg/kg/day (high dose) and groundnut oil alone (vehicle control) respectively from gestational day 6 to postnatal day (PND) 21. RESULTS: At PND 21, serum testosterone (TT) level significantly decreased in the 50, 100 mg/kg NP-treated groups compared with the control (p < 0.01). Serum estradiol (E2) level was increased with the increase in the NP concentration; a dose-effect relationship was revealed (r = 0.462, p < 0.01). At both PND 21 and PND 60, pups exposed to 100 mg/kg/day NP had an obviously higher apoptotic rate than control did. We observed a significant positive correlation between the dose of NP and the apoptotic rate (r = 0.836, p < 0.05). The number of GFAP-positive cells in rat hippocampus and integral optical density (IOD) of 100 mg/kg/day NP-treated group were much higher than the control group. GFAP mRNA expressions increased at high dose (100 mg/kg/day) (p < 0.05), and positive correlations between the GFAP mRNA expressions and NP level was observed (r = 0.586, 0.737, p < 0.05). Both the number of growth-associated protein (GAP)-43 positive cells and IOD were much lower at high dose (100 mg/kg/day) than the control at both PND 21 and PND 60 (p < 0.05). The number of GAP-43 positive cells was negatively correlated with the NP exposure dose (r = - 0.562, - 0.649, p < 0.05) at these two time points. GAP 43 mRNA expressions in the hippocampus of pups decreased dramatically at high dose (100 mg/kg/day) at both PND 21 and PND 60 compared with the control (p < 0.05). CONCLUSION: High exposure to NP might inhibit neuronal development and differentiation as indicated by the reduction of the neurotrophic factor GAP-43. PMID- 26905878 TI - The Physiology and Mechanism of Growth. PMID- 26905880 TI - Sequential molecularly imprinted solid-phase extraction methods for the analysis of resveratrol and other polyphenols. AB - Molecularly imprinted polymers (MIPs) templated with either the phytoalexin, (E) resveratrol, or its structural analog, 3,5-dihydroxy-N-(4 hydroxyphenyl)benzamide, have been used in tandem for the sequential extraction of (E)-resveratrol from aqueous peanut meal extracts in high purity and in near quantitative yields. Re-processing of the (E)-resveratrol-depleted peanut meal extract with the 3,5-dihydroxy-N-(4-hydroxyphenyl)benzamide imprinted MIP yielded additional polyphenolic components, identified as A-type procyanidins. Tandem liquid chromatography-electrospray ionization mass spectrometry confirmed the identity and purity of the isolated products. This study documents the advantages of tandem approaches with MIPs for the solid phase extraction and analysis of multiple bioactive compounds present in complex biomass waste streams. PMID- 26905879 TI - C14orf166 is a high-risk biomarker for bladder cancer and promotes bladder cancer cell proliferation. AB - BACKGROUND: C14orf166 (chromosome 14 open reading frame 166) plays a crucial role in some tumors, but its role in bladder cancer hasn't been explored. METHOD: We determined C14orf166 expression in uroepithelial cell, bladder cancer cells, normal bladder tissues and bladder cancer tissues using quantitative RT-PCR and western blot, we then analyzed the correlation between C14orf166 expression and clinicopathologic characteristics in a cohort of 149 patients with bladder cancer. Finally we downregulated C14orf166 and determined its role in the proliferation of bladder cancer cell lines using MTT assay, colony formation assay and cell cycle assay. RESULTS: We demonstrated C14orf166 was upregulated in bladder cancer cells and tissues, C14orf166 expression was significantly correlated with larger tumor size (P = 0.001), lymph node involvement (P < 0.001), histological differentiation (P < 0.001), survival time and vital states, and high C14orf166 expression correlated with poor survival, these results suggested C14orf166 served as a high-risk marker for bladder cancer. Knockdown of C14orf166 decreased the proliferation rate and colony formation ability of bladder cancer cells, and arrested cell cycle in G1/S transition. Further analysis showed that C14orf166 knockdown caused abnormal expression of key proteins for G1/S transition, such as Cyclin D1, P21, P27 and Rb phosphorylation. CONCLUSIONS: This study demonstrates that C14orf166 promotes bladder cancer cell proliferation and can be a novel prognostic biomarker for patients with bladder cancer. PMID- 26905881 TI - Characterization of cross-linked cellulosic ion-exchange adsorbents: 2. Protein sorption and transport. AB - Adsorption behavior in the HyperCel family of cellulosic ion-exchange materials (Pall Corporation) was characterized using methods to assess, quantitatively and qualitatively, the dynamics of protein uptake as well as static adsorption as a function of ionic strength and protein concentration using several model proteins. The three exchangers studied all presented relatively high adsorptive capacities under low ionic strength conditions, comparable to commercially available resins containing polymer functionalization aimed at increasing that particular characteristic. The strong cation- and anion-exchange moieties showed higher sensitivity to increasing salt concentrations, but protein affinity on the salt-tolerant STAR AX HyperCel exchanger remained strong at ionic strengths normally used in downstream processing to elute material fully during ion exchange chromatography. Very high uptake rates were observed in both batch kinetics experiments and time-series confocal laser scanning microscopy, suggesting low intraparticle transport resistances relative to external film resistance, even at higher bulk protein concentrations where the opposite is typically observed. Electron microscopy imaging of protein adsorbed phases provided additional insight into particle structure that could not be resolved in previous work on the bare resins. PMID- 26905882 TI - Comparison of isocratic retention models for hydrophilic interaction liquid chromatographic separation of native and fluorescently labeled oligosaccharides. AB - In this work, we have investigated retention of maltooligosaccharides and their fluorescent derivatives in hydrophilic interaction liquid chromatography using four different stationary phases. The non-derivatized maltooligosaccharides (maltose to maltoheptaose) and their derivatives with 2-aminobenzoic acid, 2 aminobenzamide, 2-aminopyridine and 8-aminonaphthalene-1,3,6-trisulfonic acid were analyzed on silica gel, aminopropyl silica, amide (carbamoyl-bonded silica) and ZIC-HILIC zwitterionic sulfobetain bonded phase. The partitioning of the analytes between the bulk mobile phase and adsorbed water-rich layer, polar and ionic interactions of analytes with stationary phase have been evaluated and compared. The effects of the mobile phase additives (0.1% (v/v) of acetic acid and ammonium acetate in concentration range 5-30 mmol L(-1)) on retention were described. The suitability of different models for prediction of retention was tested including linear solvent strength model, quadratic model, mixed-mode model, and empirical Neue-Kuss model. The mixed-mode model was extended to the parameter describing the contribution of monomeric glucose unit to the retention of non-derivatized and derivatized maltooligosaccharides, which was used for evaluation of contribution of both, oligosaccharide backbone and end-group to retention. PMID- 26905883 TI - A chemical profiling solution for Chinese medicine formulas using comprehensive and loop-based multiple heart-cutting two-dimensional liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. AB - Chinese medicine formulas represent an excellent illustration for "complex matrix". The complexity lies in a big array of small molecules with high chemical diversity. The present paper describes a novel chemical profiling solution for complex matrix by combining comprehensive and multiple heart-cutting two dimensional liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (2DLC/qTOF-MS). This solution includes method optimization, combinational separation, and structural characterization. It was exemplified by fully profiling the chemical constituents of a four-herb traditional Chinese medicine formula, Gegen-Qinlian Decoction (GQD). GQD was separated by a RP * RP (C18 * Phenyl-Hexyl) 2DLC system, and eluted with acidic * alkaline mobile phases with an optimized shift gradient elution program. In the comprehensive 2DLC mode, 280 peaks were detected, and 125 compounds were characterized within 42 minutes. The multiple heart-cutting (MHC) mode extended the (2)D modulation time to 3.0 min to effectively separate the minor compounds. The (1)D eluate within 4.4 min was loaded into eleven 40-MUL loops. These fractions were successively separated by (2)D to resolve 13 additional compounds. The combination of comprehensive and MHC 2DLC/qTOF-MS provides a powerful technique for global chemical profiling of Chinese medicine formulas and other complex systems. PMID- 26905884 TI - Studies on the application of temperature-responsive ion exchange polymers with whey proteins. AB - Several new types of temperature-responsive ion exchange resins of different polymer composition have been prepared by grafting the products from the co polymerisation of N-phenylacrylamide, N-iso-propylacrylamide and acrylic acid derivatives onto cross-linked agarose. Analysis of the binding isotherms for these different resins obtained under batch adsorption conditions indicated that the resin based on N-iso-propylacrylamide containing 5% (w/w) N-phenylacrylamide and 5% (w/w) acrylic acid resulted in the highest adsorption capacity, Bmax, for the whey protein, bovine lactoferrin, e.g. 14 mg bovine lactoferrin/mL resin at 4 degrees C and 62 mg bovine lactoferrin/mL resin at 40 degrees C, respectively. Under dynamic loading conditions at 40 degrees C, 94% of the loaded bovine lactoferrin on a normalised mg protein per mL resin basis was adsorbed by this new temperature-responsive ion-exchanger, and 76% was eluted by a single cycle temperature shift to 4 degrees C without varying the composition of the 10mM sodium dihydrogen phosphate buffer, pH 6.5, or the flow rate. The binding characteristics of these different ion exchange resins with bovine lactoferrin were also compared to results obtained using other resins based on N isopropylacrylamide but contained N-tert-butylacrylamide rather than N phenylacrylamide, where the corresponding dynamic capture and release properties for bovine lactoferrin required different temperature conditions of 20 degrees C and 50 degrees C, respectively for optimal desorption/adsorption. The cationic protein, bovine lactoperoxidase, was also adsorbed and desorbed with these temperature-responsive resins under similar conditions of changing temperature, whereas the anionic protein, bovine beta-lactoglobulin, was not adsorbed under this regime of temperature conditions but instead eluted in the flow-through. PMID- 26905885 TI - Relevant Differences in Perception and Knowledge of Professionals in Different Spanish Autonomous Communities Regarding Availability of Resources for Patients with Dual disorders. AB - OBJECTIVES: To assess the knowledge of health professionals attending patients with dual disorders about specific resources for patients with this condition in different Spanish regions. METHODS: Observational, cross-sectional, multicenter study to compare the perceptions of healthcare professionals (n=659) with reality regarding specific resources available for patients with dual disorders in Spain. The professionals completed an online questionnaire. Nineteen commissioners and managers responsible for national and regional substance abuse programs also completed the questionnaire. RESULTS: A representative sample of professionals from each community (553 centers in 235 Spanish cities) participated in the study. Most participants (93.2%) felt that specific resources for patients with dual disorders are needed. High percentages of professionals thought that there were no specific workshops (88.4%), subacute units (83.1%), day hospitals (82.8%), specific day centers (78.5%), or outpatient programs (73.2%) for patients with dual disorders. The real knowledge of professionals regarding the existence of specific resources varied according to the type of resource and autonomous community. The professionals generally underestimated the number of units available in their communities. CONCLUSIONS: There were clear differences in the real knowledge that healthcare professionals had about the resources available for patients with dual disorders in relation to the autonomous community where they were practicing. Actions are needed to harmonize knowledge nationally, for example, a single registry, white paper, or a national program for patients with dual disorders. PMID- 26905886 TI - Psychometric properties of the Plutchik´s Violence Risk Scale on adolescent sample of Spanish-speaking population. AB - OBJETIVE: The objective of the present study was the validation and scaling of the Plutchik's Violence Risk Scale (EV) in adolescent Spanish-speaking population. METHODS: For this purpose, a sample of adolescents from El Salvador, Mexico and Spain was obtained. The sample consisted of 1035 participants with a mean age of 16.2. There were 450 adolescents from forensic population (those who committed crime) and 585 adolescents from normal population (no crime committed). RESULTS: The internal consistency of the EV was estimated by Cronbach's alpha coefficient and with a value of 0.782. As for validity, the factorial structures found explain a large proportion of the variance (53.385%); the convergent validity was estimated by the correlation between the dimensions found, the EV and sociodemographic, criminological and personality variables. The developed scales are presented, for the first time in a cross-cultural sample, differentiating between gender and continent. CONCLUSIONS: Consequently, the obtained results suggest that the EV is a valid and reliable instrument within adolescent Spanish-speaking population. Furthermore, it is a quick scale, easy to apply, which is something valuable in forensic assessment. PMID- 26905887 TI - Risk factor assessment and counselling for 12 months reduces metabolic and cardiovascular risk in overweight or obese patients with schizophrenia spectrum disorders: The CRESSOB study. AB - BACKGROUND: Metabolic syndrome (MS) and cardiovascular risk factors (CRF) have been associated with patients with schizophrenia. The main objective is to assess the evolution of CRF and prevalence of MS for 12 months in a cohort of overweight patients diagnosed with schizophrenia schizophreniform disorder or schizoaffective disorder in which the recommendations for the assessment and control of metabolic and cardiovascular risk were applied. METHODS: The Control of Metabolic and Cardiovascular Risk in Patients with Schizophrenia and Overweight (CRESSOB) study is a 12-month, observational, prospective, open-label, multicentre, naturalistic study including 109 community mental health clinics of Spain. The study included a total of 403 patients, of whom we could collect all variables related to CRF and MS in 366 patients. Of these 366 patients, 286 completed the follow-up, (baseline, months 3, 6 and 12) where they underwent a complete physical examination and a blood test (glucose, cholesterol and triglycerides), they were asked about their health-related habits (smoking, diet and exercise) and they were given a series of recommendations to prevent cardiovascular risk and MS. RESULTS: A total of 403 patients were included, 63% men, mean age (mean; (SD)) 40.5 (10.5) years. After 12 months, the study showed statistically significant decrease in weight (p<0.0001), waist circumference (p<0.0001), BMI (p<0.0001), blood glucose (p=0.0034), total cholesterol (p<0.0001), HDL cholesterol (p=0.02), LDL cholesterol (p=0.0023) and triglycerides (p=0.0005). There was a significant reduction in the percentage of smokers (p=0.0057) and in the risk of heart disease at 10 years (p=0.0353). CONCLUSION: Overweight patients with schizophrenia who receive appropriate medical care, including CRF monitoring and control of health-related habits experience improvements with regard to most CRFs. PMID- 26905888 TI - Social cognition interventions for persons with schizophrenia: evidence and clinical practice guidelines. AB - Although most of the research conducted up to now has shown that interventions in social cognition are effective in the rehabilitation of persons with schizophrenia, there are still no clinical practice recommendations on the topic. Their development could facilitate the clinical work, resource management and the care provided to persons with such a disorder. This article addresses this need and performs a systematic review of the identified high-quality scientific evidence and develops clinical practice recommendations. A total of 40 clinical trials and 1 meta-analysis evaluating the effects of social cognition interventions for persons with schizophrenia were selected for the present study. Taking into account the evidence available and its quality, the authors developed three clinical practice recommendations on the positive effects of these interventions. The analysis of the evidence of the quality of the studies shows that more randomized controlled trials with larger sample sizes and longer follow ups are needed in order to establish more accurately the efficacy and effectiveness of social cognition interventions and therefore to favor the generalization of the results. PMID- 26905889 TI - Clozapine-induced paralytic ileus. PMID- 26905890 TI - Feasibility of an integrated mindfulness and Mediterranean lifestyle program. PMID- 26905891 TI - Locating influential nodes via dynamics-sensitive centrality. AB - With great theoretical and practical significance, locating influential nodes of complex networks is a promising issue. In this paper, we present a dynamics sensitive (DS) centrality by integrating topological features and dynamical properties. The DS centrality can be directly applied in locating influential spreaders. According to the empirical results on four real networks for both susceptible-infected-recovered (SIR) and susceptible-infected (SI) spreading models, the DS centrality is more accurate than degree, k-shell index and eigenvector centrality. PMID- 26905892 TI - Epidemiologic Evidence to Guide the Understanding and Prevention of Gun Violence. AB - Gunfire from assaults, suicides, and unintentional shootings exacts an enormous burden on public health globally. The epidemiologic reviews in this special issue enhance our understanding of various forms of gun violence, inform interventions, and help chart directions for future research. The available science, however, is limited to answer many important questions necessary for mounting successful efforts to reduce gun violence. Certain data are lacking, and there are numerous analytical challenges to deriving unbiased estimates of policy impacts. Significant investments in research over the long term are warranted to answer questions central to successful prevention of gun violence. PMID- 26905893 TI - The Relationship Between Controlled Substances and Violence. AB - A causal relationship between controlled substances and firearm violence has been widely assumed in the United States, and federal law prohibits individuals who are "unlawful users of or addicted to any controlled substance" from purchasing or possessing firearms (68 FR 3750. 2003. Codified at 27 CFR S478.11). However, the law does a poor job of defining "unlawful users," resulting in recent calls for a revised, actionable definition. Such a definition should be informed by research evidence, but to date the epidemiologic research on the relationship between controlled substances and violence has not been comprehensively reviewed. The initial goal of this review was to summarize the best available evidence on the relationship between controlled substances and firearm violence, but only 1 study specific to firearm violence was identified. We therefore reviewed studies of this relationship using broader measures of interpersonal violence and suicide, all of which included but were not limited to firearm violence, and measures of illicit firearm carrying. Prospective longitudinal studies (n = 22) from 1990 to 2014 were identified by using searches of online databases and citation tracking. Information was extracted from each study by using a standardized protocol. Quality of evidence was independently assessed by 2 reviewers. Aggregate measures of controlled substance use were associated with increased interpersonal violence and suicide, but evidence regarding the relationship between specific substances and violence was mixed. Involvement in illegal drug sales was consistently associated with interpersonal violence. To effectively revise extant federal law and delineate appropriate prohibiting criteria, more research is needed to understand the relationship between controlled substances and firearm violence. PMID- 26905894 TI - Clinician Attitudes, Screening Practices, and Interventions to Reduce Firearm Related Injury. AB - Firearm injury is a leading cause of injury-related morbidity and mortality in the United States. We sought to systematically identify and summarize existing literature on clinical firearm injury prevention screening and interventions. We conducted a systematic search of PubMed, Web of Science, Cumulative Index of Nursing and Allied Health Literature (CINAHL), PsycInfo, and ClinicalTrials.gov for English-language original research (published 1992-2014) on clinical screening methods, patient-level firearm interventions, or patient/provider attitudes on the same. Unrelated studies were excluded through title, abstract, and full-text review, and the remaining articles underwent data abstraction and quality scoring. Of a total of 3,260 unique titles identified, 72 were included in the final review. Fifty-three articles examined clinician attitudes/practice patterns; prior training, experience, and expectations correlated with clinicians' regularity of firearm screening. Twelve articles assessed patient interventions, of which 6 were randomized controlled trials. Seven articles described patient attitudes; all were of low methodological quality. According to these articles, providers rarely screen or counsel their patients-even high-risk patients-about firearm safety. Health-care-based interventions may increase rates of safe storage of firearms for pediatric patients, suicidal patients, and other high-risk groups. Some studies show that training clinicians can increase rates of effective firearm safety screening and counseling. Patients and families are, for the most part, accepting of such screening and counseling. However, the current literature is, by and large, not high quality. Rigorous, large-scale, adequately funded studies are needed. PMID- 26905895 TI - What Do We Know About the Association Between Firearm Legislation and Firearm Related Injuries? AB - Firearms account for a substantial proportion of external causes of death, injury, and disability across the world. Legislation to regulate firearms has often been passed with the intent of reducing problems related to their use. However, lack of clarity around which interventions are effective remains a major challenge for policy development. Aiming to meet this challenge, we systematically reviewed studies exploring the associations between firearm related laws and firearm homicides, suicides, and unintentional injuries/deaths. We restricted our search to studies published from 1950 to 2014. Evidence from 130 studies in 10 countries suggests that in certain nations the simultaneous implementation of laws targeting multiple firearms restrictions is associated with reductions in firearm deaths. Laws restricting the purchase of (e.g., background checks) and access to (e.g., safer storage) firearms are also associated with lower rates of intimate partner homicides and firearm unintentional deaths in children, respectively. Limitations of studies include challenges inherent to their ecological design, their execution, and the lack of robustness of findings to model specifications. High quality research on the association between the implementation or repeal of firearm legislation (rather than the evaluation of existing laws) and firearm injuries would lead to a better understanding of what interventions are likely to work given local contexts. This information is key to move this field forward and for the development of effective policies that may counteract the burden that firearm injuries pose on populations. PMID- 26905900 TI - Erratum to: Prolonged use of a proton pump inhibitor reduces microbial diversity: implications for Clostridium difficile susceptibility. PMID- 26905901 TI - The impact of treatment condition and the lagged effects of PTSD symptom severity and alcohol use on changes in alcohol craving. AB - Given the high rates of comorbidity between posttraumatic stress disorder (PTSD) and substance use disorder (SUD), we investigated an integrated treatment for these disorders. Individuals with comorbid PTSD and alcohol dependence were randomized to receive naltrexone or placebo, with or without prolonged exposure (PE). All participants also received BRENDA (supportive counseling). The naltrexone plus PE group showed a greater decline in alcohol craving symptoms than those in the placebo with no PE group. The PE plus placebo and the naltrexone without PE groups did not differ significantly from the placebo with no PE group in terms of alcohol craving. No treatment group differences were found for percentage of drinking days. Alcohol craving was moderated by PTSD severity, with those with higher PTSD symptoms showing faster decreases in alcohol craving. Both PTSD and alcohol use had a lagged effect on alcohol craving, with changes in PTSD symptoms and percentage of days drinking being associated with subsequent changes in craving. These results support the relationship between greater PTSD symptoms leading to greater alcohol craving and suggest that reducing PTSD symptoms may be beneficial to reducing craving in those with co-occurring PTSD/SUD. PMID- 26905903 TI - Gastric Xanthomatosis: A Rare Presentation of a Common Disorder. PMID- 26905902 TI - Intracellular delivery of antibodies by chimeric Sesbania mosaic virus (SeMV) virus like particles. AB - The therapeutic potential of antibodies has not been fully exploited as they fail to cross cell membrane. In this article, we have tested the possibility of using plant virus based nanoparticles for intracellular delivery of antibodies. For this purpose, Sesbania mosaic virus coat protein (CP) was genetically engineered with the B domain of Staphylococcus aureus protein A (SpA) at the betaH-betaI loop, to generate SeMV loop B (SLB), which self-assembled to virus like particles (VLPs) with 43 times higher affinity towards antibodies. CP and SLB could internalize into various types of mammalian cells and SLB could efficiently deliver three different monoclonal antibodies-D6F10 (targeting abrin), anti-alpha tubulin (targeting intracellular tubulin) and Herclon (against HER2 receptor) inside the cells. Such a mode of delivery was much more effective than antibodies alone treatment. These results highlight the potential of SLB as a universal nanocarrier for intracellular delivery of antibodies. PMID- 26905904 TI - Inflammatory Bowel Disease Affects the Outcome of Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection. AB - BACKGROUND & AIMS: A significant fraction of patients with recurrent Clostridium difficile infections (CDI) have inflammatory bowel disease (IBD). Fecal microbiota transplantation (FMT) can break the cycle of CDI recurrence and can be performed without evaluation of the colon. We evaluated the efficacy of colonoscopic FMT in patients with and without IBD, and whether we could identify IBD in patients during this procedure. METHODS: We collected clinical meta-data and colonoscopy results from 272 consecutive patients that underwent FMT for recurrent CDI at the University of Minnesota from 2008 through 2015. Patients had at least 2 spontaneous relapses of CDI following their initial episode and did not clear the infection after 1 extended antibiotic regimen. We collected random mucosal biopsies from patients' right colons to identify lymphocytic or collagenous colitis during the FMT procedure. Failure or success in clearing CDI was determined within or at 2 months after the FMT. RESULTS: Of patients undergoing FMT, 15% had established IBD and 2.6% were found to have IBD during the FMT procedure. A single colonoscopic FMT cleared CDI from 74.4% of patients with IBD and 92.1% of patients without IBD (P = .0018). Patients had similar responses to FMT regardless of immunosuppressive therapy. More than one-quarter of patients with IBD (25.6%) had a clinically significant flare of IBD after FMT. Lymphocytic colitis was documented in 7.4% of patients with endoscopically normal colon mucosa; only 3 of these patients (20%) required additional treatment for colitis after clearance of CDI. CONCLUSIONS: Based on an analysis of 272 patients, FMT is somewhat less effective in clearing recurrent CDI from patients with IBD, compared with patients without IBD, regardless of immunosuppressive therapy. More than 25% of patients with IBD have a disease flare following FMT. Lymphocytic colitis did not affect the outcome of FMT, but a small fraction of these patients required pharmacologic treatment after the procedure. PMID- 26905905 TI - Frequency and Features of Duodenal Adenomas in Patients With MUTYH-Associated Polyposis. AB - BACKGROUND & AIMS: MUTYH-associated polyposis (MAP) is similar to familial adenomatous polyposis (FAP), in that it increases the risk for duodenal adenomas and cancer. Almost all patients with FAP develop duodenal adenomas and 5% develop duodenal cancer. Little is known about the prevalence of duodenal adenomas and cancer in patients with MAP, but current surveillance recommendations are the same for patients with FAP-they should begin surveillance when they are 25 years old. We aimed to assess the prevalence, extent, and progression of duodenal adenomas in patients with MAP and evaluate upper gastrointestinal tract surveillance recommendations. METHODS: In a retrospective study, we collected data on all patients (n = 92) with MAP undergoing surveillance esophagogastroduodenoscopy from registries at St Mark's Hospital (London, UK) and the Academic Medical Center (Amsterdam, The Netherlands) from 2002 through 2014. We collected information on adenoma development, age at adenoma detection, interventions, and disease progression. RESULTS: Duodenal adenomas were detected in 31 patients (34%), at a median age of 50 years. When duodenal polyposis first was detected, it was Spigelman stages I or II in 84% of patients; most had few small polyps, without high-grade dysplasia or villous features. Subsequent esophagogastroduodenoscopy evaluation of 18 of these patients found that 14 (78%) had Spigelman stages 0 to II disease (median follow-up period, 7.8 y). Disease progressed in stage in 6 patients, over 9.5 years, because of lesion size or villous features (2 reached stage IV disease). Adenomas were down-staged in 8 patients after biopsy or polypectomy analyses, and were unchanged for 3 patients. CONCLUSIONS: In a data analysis from 92 patients with MAP, duodenal polyposis seemed to develop less frequently than in patients with FAP, and developed at a later age. Increasing lesion size and villous change appear to promote adenoma progression, rather than polyp number or dysplasia. It may be time to consider a new staging system for patients with MAP, to better determine disease severity and surveillance strategies. PMID- 26905906 TI - Effects of Bariatric Surgery on Outcomes of Patients With Acute Pancreatitis. AB - BACKGROUND & AIMS: The prevalence of obesity and number of patients undergoing bariatric surgery are increasing. Obesity has adverse effects in patients with acute pancreatitis (AP). We investigated whether bariatric surgery affects outcomes of patients with AP. METHODS: We performed a retrospective study, collecting data from the US Nationwide Inpatient Sample (2007-2011) on all adult inpatients (>=18 years) with a principal diagnosis of AP (n = 1,342,681). We compared primary clinical outcomes (mortality, acute kidney injury, and respiratory failure) and secondary outcomes related to healthcare resources (hospital stay and charges) among patient groups using univariate and multivariate analyses. We performed a propensity score-matched analysis to compare outcomes of patients with versus without bariatric surgery. RESULTS: Of patients admitted to the hospital with a principal diagnosis of AP, 14,332 (1.07%) had undergone bariatric surgery. The number of patients that underwent bariatric surgery doubled, from 1801 in 2007 to 3928 in 2011 (P < .001). AP in patients that had undergone bariatric surgery was most frequently associated with gallstones. Multivariate analysis associated prior bariatric surgery with decreased mortality (odds ratio, 0.41; 95% confidence interval, 0.18-0.92), shorter duration of hospitalization (0.65 days shorter; P < .001), and lower hospital charges ($3558 lower) than in patients with AP not receiving bariatric surgery (P < .001). A propensity score-matched cohort analysis found that mortality and odds of acute kidney injury were similar between patients with versus without history of bariatric surgery, whereas respiratory failure was less frequent in patients who received bariatric surgery (1.34% vs 4.42%; P < .001). CONCLUSIONS: Prior bariatric surgery in patients hospitalized with AP is not adversely associated with in-hospital mortality, development of organ failure, or healthcare resource use. Bariatric surgery may mitigate the obesity-associated adverse prognostication in AP. These observations are pertinent for future research, because the prevalence of obesity and AP-related hospitalizations is increasing. PMID- 26905908 TI - Crystal Structure of Alcohol Oxidase from Pichia pastoris. AB - FAD-dependent alcohol oxidases (AOX) are key enzymes of methylotrophic organisms that can utilize lower primary alcohols as sole source of carbon and energy. Here we report the crystal structure analysis of the methanol oxidase AOX1 from Pichia pastoris. The crystallographic phase problem was solved by means of Molecular Replacement in combination with initial structure rebuilding using Rosetta model completion and relaxation against an averaged electron density map. The subunit arrangement of the homo-octameric AOX1 differs from that of octameric vanillyl alcohol oxidase and other dimeric or tetrameric alcohol oxidases, due to the insertion of two large protruding loop regions and an additional C-terminal extension in AOX1. In comparison to other alcohol oxidases, the active site cavity of AOX1 is significantly reduced in size, which could explain the observed preference for methanol as substrate. All AOX1 subunits of the structure reported here harbor a modified flavin adenine dinucleotide, which contains an arabityl chain instead of a ribityl chain attached to the isoalloxazine ring. PMID- 26905907 TI - Statin Use Is Associated With Reduced Risk of Colorectal Cancer in Patients With Inflammatory Bowel Diseases. AB - BACKGROUND & AIMS: Inflammatory bowel diseases (IBDs) such as Crohn's disease and ulcerative colitis are associated with an increased risk of colorectal cancer (CRC). Chemopreventive strategies have produced weak or inconsistent results. Statins have been associated inversely with sporadic CRC. We examined their role as chemopreventive agents in patients with IBD. METHODS: We collected data from 11,001 patients with IBD receiving care at hospitals in the Greater Boston metropolitan area from 1998 through 2010. Diagnoses of CRC were determined using validated International Classification of Diseases, 9th revision, Clinical Modification codes. Statin use before diagnosis was assessed through analysis of electronic prescriptions. We performed multivariate logistic regression analyses, adjusting for potential confounders including primary sclerosing cholangitis, smoking, increased levels of inflammation markers, and CRC screening practices to identify an independent association between statin use and CRC. We performed sensitivity analyses using propensity score adjustment and variation in the definition of statin use. RESULTS: In our cohort, 1376 of the patients (12.5%) received 1 or more prescriptions for a statin. Patients using statins were more likely to be older, male, white, smokers, and have greater comorbidity than nonusers. Over a follow-up period of 9 years, 2% of statin users developed CRC compared with 3% of nonusers (age-adjusted odds ratio, 0.35; 95% confidence interval, 0.24-0.53). On multivariate analysis, statin use remained independently and inversely associated with CRC (odds ratio, 0.42; 95% confidence interval, 0.28-0.62). Our findings were robust on a variety of sensitivity and subgroup analyses. CONCLUSIONS: Statin use was associated inversely with the risk of CRC in a large IBD cohort. Prospective studies on the role of statins as chemopreventive agents are warranted. PMID- 26905910 TI - Clinical Manifestations of Isolated Elevated Homocysteine-Induced Peripheral Neuropathy in Adults. AB - OBJECTIVE: To characterize the clinical features of isolated elevated plasma homocysteine (eHcy)-induced peripheral neuropathy (IHIN) in adults. METHODS: Charts of subjects with the diagnosis of IHIN who visited neuromuscular clinic from January 01, 2012 to September 30, 2014 were reviewed. Subjects with identifiable etiologies for neuropathy, such as B12/folate deficiency; metabolic, toxic, endocrinologic, infectious/inflammatory renal or liver diseases; or traumatic nerve injury, were excluded. Their clinical presentations were recorded and analyzed. RESULTS: Thirty subjects (age: 63.2 +/- 14.8 years, 13 males) were included. They all had an isolated increased homocysteine level (15.4 +/- 5.3 MUmol/L) but normal levels of B12, folate, and methylmalonic acid. Of 30, 14 (46.7%) had numb feet, 11 (36.7%) had numb hands, 7 (23.3%) had pain in lower extremities, and 10 (33.3%) had tingling in feet. Distal sensory deficits were present in 18/30 (60%) patients. Distal limb weakness was seen in 4 and decreased tendon reflexes in 12 patients. CONCLUSIONS: Sensory deficits are predominant components of IHIN. Characterizing clinical features of IHIN would help better understand eHcy-related neuropathy and improve its management. PMID- 26905909 TI - Primary Lateral Sclerosis and Early Upper Motor Neuron Disease: Characteristics of a Cross-Sectional Population. AB - OBJECTIVES: The goals of this study were to characterize clinical and electrophysiologic findings of subjects with upper motor neuron disease and to explore feasibility of clinical trials in this population. METHODS: Twenty northeast amyotrophic lateral sclerosis consortium (northeast amyotrophic lateral sclerosis) sites performed chart reviews to identify active clinical pure upper motor neuron disease patients. Patients with hereditary spastic paraplegia or meeting revised El Escorial electrodiagnostic criteria for amyotrophic lateral sclerosis were excluded. Patients were classified into 2 groups according to the presence or absence of minor electromyography (EMG) abnormalities. RESULTS: Two hundred thirty-three subjects with upper motor neuron disease were identified; 217 had available EMG data. Normal EMGs were seen in 140 subjects, and 77 had minor denervation. Mean disease duration was 84 (+/-80) months for the entire cohort with no difference seen between the 2 groups. No difference was seen in clinical symptoms, disability, or outcome measures between the 2 groups after correcting for multiple comparisons. CONCLUSIONS: Minor EMG abnormalities were not associated with phenotypic differences in a clinical upper motor neuron disease population. These findings suggest that subtle EMG abnormalities can not necessarily be used as a prognostic tool in patients with clinical upper motor neuron disease. This study also demonstrates the availability of a large number of patients with upper motor neuron diseases within the northeast amyotrophic lateral sclerosis network and suggests feasibility for conducting clinical trials in this population. PMID- 26905911 TI - Safety and Efficacy of Subcutaneous Immunoglobulin in the Treatment of Neuromuscular Disorders. AB - Many neuromuscular diseases may be treated with immunoglobulins. In the United States, the major form of immunoglobulin used is intravenous (IV). Recently, there has been an increased interest in research regarding the use of subcutaneous immunoglobulin (SCIg), mainly for improved patient quality of life, convenience, potential for fewer systemic adverse events, and avoiding wear-off. The widespread use of the subcutaneous formulation in neurology has been affected by some limitations, mainly the smaller volume and higher frequency of infusions compared to IV administration. Also, there are different pharmacokinetic properties that should be considered to evaluate whether they change the immunomodulatory effect. There are several formulations available that address some limitations. Several studies have assessed efficacy, safety, and quality of life of SCIg in neurology. This review article summarizes the current evidence for the use of SCIg in neuromuscular diseases. It also addresses the pharmacokinetic differences and the different formulations available. The current available preliminary evidence indicates that SCIg is at least as effective as the IV formulations. PMID- 26905912 TI - Cardiac Involvement in Peripheral Neuropathies. AB - Cardiac autonomic neuropathy (CAN) is the least recognized and understood complication of peripheral neuropathy. However, because of its potential adverse effects including sudden death, CAN is one of the most important forms of autonomic neuropathies. CAN presents with different clinical manifestations including postural hypotension, exercise intolerance, fluctuation of blood pressure and heart rate, arrhythmia, and increased risk of myocardial infarction. In this article, the prevalence, clinical presentations, and management of cardiac involvement in certain peripheral neuropathies, including diabetic neuropathy, Guillain-Barre syndrome, chronic inflammatory polyneuropathy, human immunodeficiency virus-associated neuropathy, hereditary neuropathies, and amyloid neuropathy are examined in detail. PMID- 26905913 TI - A Case Series of Patients With Autoimmune Myasthenia Gravis in Association With Invasive Thymoma. AB - OBJECTIVES: In some patients, autoimmune myasthenia gravis (MG) is associated with thymic hyperplasia or thymoma, and in some patients the thymoma is invasive. Little is known about the clinical course of subjects who present with MG and are found to have invasive thymoma. METHODS: We reviewed the patients at our clinic with MG and invasive thymoma, and have described their clinical features. RESULTS: Six MG patients were diagnosed with invasive thymoma. The subjects had extensive multimodal therapy. Two subjects died from uncontrolled neuromuscular respiratory failure despite aggressive immunosuppression, 2 subjects had other autoimmune disorders (Morvan syndrome and polymyositis), and 2 subjects are controlled on immunosuppression. CONCLUSIONS: Patients with invasive thymoma and MG can have a poor outcome, with difficulty in controlling myasthenic symptoms and can have other clinically important autoimmune diseases. PMID- 26905914 TI - Unexpected Rapid Improvement and Neurogenic Stunned Myocardium in a Patient With Acute Motor Axonal Neuropathy: A Case Report and Literature Review. AB - Acute Motor Axonal Neuropathy-type Guillain-Barre Syndrome (GBS) is a subset of GBS with either a rapidly improving or protracted course that was first described in China. We describe a 27-year-old previously healthy woman with weakness that progressed to complete tetraplegia and areflexia within 2 weeks after an upper respiratory illness. A lumbar puncture performed 4 days after onset of neurologic symptoms was inconclusive for GBS, and electromyography revealed complete motor axonal neuropathy. The patient had Mycoplasma pneumoniae in her nares and blood, and several antiganglioside antibodies in her blood. She was treated with plasmapheresis, antibiotics, and physical therapy. Her motor function and reflexes improved rapidly with treatment, and she was able to ambulate within 3 weeks. She also experienced cardiomyopathy, which improved with plasmapheresis. We report a rare case of Mycoplasma pneumonia-associated acute motor axonal neuropathy-type GBS presenting with complete tetraplegia, areflexia, and neurogenic stunned myocardium that rapidly improved with plasmapheresis. PMID- 26905915 TI - Rapidly Progressive Transthyretin-Mediated Amyloidosis in a Domino Liver Transplant Recipient of a Ser23Asn Donor. AB - Domino liver transplantation, in which the liver of a patient with transthyretin mediated amyloidosis is transplanted into another patient, has been an established procedure performed at several centers across the world. The risk of developing systemic amyloidosis in transthyretin-mediated amyloidosis liver transplant recipients is a topic of ongoing investigation. We report a case of rapidly progressive transthyretin amyloidosis in a patient who received a liver from a donor with a rare Ser23Asn mutation. We advise exercising caution when considering domino liver transplantation in patients with this particular mutation. PMID- 26905918 TI - The comparative short-term outcome of bipolar II disorder patients variably meeting or not meeting DSM-5 duration criteria following lamotrigine treatment. AB - There is accruing clinical and empirical evidence supporting the efficacy of lamotrigine as a treatment for bipolar II disorder. However, the treatment response experienced by those with 'short duration' hypomania (or 'other specified' bipolar disorder) has been under-researched. We reviewed a clinical sample of 123 patients diagnosed with a bipolar II disorder three months following their initial assessment. A research interview evaluated treatment strategies implemented, depressive and hypomanic episode pattern and functional outcomes. Of patients who had achieved a minimum level of 75 mg of lamotrigine, n = 51 were assigned to the BP II disorder group (i.e., hypomanic episodes lasted four days or longer) and n = 28 to the short duration group (i.e., hypomanic episodes always lasted less than four days). There were no significant differences between the two groups at the three-month follow-up on self-report measures of changes in depressive and hypomanic episode pattern or functioning across six domains (i.e., intimate relationships, family relationships, friendships, work relationships, work performance, overall quality of life), and with the majority of patients reporting some level of improvement. Study limitations include being an observational, uncontrolled design with a relatively small sample size for detecting statistical differences. Nonetheless, lamotrigine appeared to be a suitable medication to be trialled in patients who alternate between depressive episodes and short periods of hypomania, (as for those with DSM-defined hypomanic episodes), and should prompt further investigation. PMID- 26905919 TI - Atomoxetine could improve intra-individual variability in drug-naive adults with attention-deficit/hyperactivity disorder comparably with methylphenidate: A head to-head randomized clinical trial. AB - OBJECTIVE: Intra-individual variability in reaction time (IIV-RT) is common in individuals with attention-deficit/hyperactivity disorder (ADHD). It can be improved by stimulants. However, the effects of atomoxetine on IIV-RT are inconclusive. We aimed to investigate the effects of atomoxetine on IIV-RT, and directly compared its efficacy with methylphenidate in adults with ADHD. METHODS: An 8-10 week, open-label, head-to-head, randomized clinical trial was conducted in 52 drug-naive adults with ADHD, who were randomly assigned to two treatment groups: immediate-release methylphenidate (n=26) thrice daily (10-20 mg per dose) and atomoxetine once daily (n=26) (0.5-1.2 mg/kg/day). IIV-RT, derived from the Conners' continuous performance test (CCPT), was represented by the Gaussian (reaction time standard error, RTSE) and ex-Gaussian models (sigma and tau). Other neuropsychological functions, including response errors and mean of reaction time, were also measured. Participants received CCPT assessments at baseline and week 8-10 (60.4+/-6.3 days). RESULTS: We found comparable improvements in performances of CCPT between the immediate-release methylphenidate- and atomoxetine-treated groups. Both medications significantly improved IIV-RT in terms of reducing tau values with comparable efficacy. In addition, both medications significantly improved inhibitory control by reducing commission errors. CONCLUSION: Our results provide evidence to support that atomoxetine could improve IIV-RT and inhibitory control, of comparable efficacy with immediate-release methylphenidate, in drug-naive adults with ADHD. Shared and unique mechanisms underpinning these medication effects on IIV-RT awaits further investigation. PMID- 26905920 TI - Antipsychotic polypharmacy and augmentation strategies prior to clozapine initiation: a historical cohort study of 310 adults with treatment-resistant schizophrenic disorders. AB - RATIONALE: Antipsychotic polypharmacy (APP) is commonly used in schizophrenia despite a lack of robust evidence for efficacy, as well as evidence of increased rates of adverse drug reactions and mortality. OBJECTIVES: We sought to examine APP and the use of other adjunctive medications in patients with treatment resistant schizophrenic disorders (ICD-10 diagnoses F20-F29) immediately prior to clozapine initiation, and to investigate clinical and sociodemographic factors associated with APP use in this setting. METHODS: Analysis of case notes from 310 patients receiving their first course of clozapine at the South London and Maudsley NHS Trust (SLaM) was undertaken using the Clinical Record Interactive Search (CRIS) case register. Medication taken immediately prior to clozapine initiation was recorded, and global clinical severity was assessed at time points throughout the year prior to medication assessment using the Clinical Global Impression - Severity scale (CGI-S). Logistic regression was used to investigate factors associated with APP. RESULTS: The point prevalence of APP prior to clozapine initiation was 13.6% (n=42), with 32.6% of subjects prescribed adjuvant psychotropic medications. APP was associated with increasing number of adjuvant medications (odds ratio (OR) 1.97, 95% confidence interval (CI) 1.27-3.06), concurrent depot antipsychotic prescription (OR 2.64, CI 1.24-5.62), concurrent antidepressant prescription (OR 4.40, CI 1.82-10.63) and a CGI-S over the previous year within the two middle quartiles (Quartile 2 vs 1 OR 6.19, CI 1.81 21.10; Quartile 3 vs 1 OR 4.45, CI 1.29-15.37; Quartile 4 vs 1 OR 1.88, CI 0.45 7.13). CONCLUSIONS: APP and augmentation of antipsychotics with antidepressants, mood stabilizers and benzodiazepines are being employed in treatment-resistant schizophrenia prior to clozapine. The conservative APP rate observed may have been influenced by an initiative within SLaM that reduced APP rates during the study window. Efforts to reduce the use of poorly evidenced prescribing should focus on adjuvant medications as well as APP. PMID- 26905923 TI - Electronic and steric Tolman parameters for proazaphosphatranes, the superbase core of the tri(pyridylmethyl)azaphosphatrane (TPAP) ligand. AB - The Tolman electronic parameters (TEP) and cone angles were experimentally measured for a series of substituted proazaphosphatrane ligands by synthesizing their respective Ni(L(R))(CO)3 complexes, where L = P(RNCH2CH2)3N and R = Me, iPr, iBu and Bz. The complexes Ni(L(Me))(CO)3 (), Ni(L(iPr))(CO)3 (), Ni(L(iBu))(CO)3 () and Ni(L(Bz))(CO)3 () display CO vibrational frequencies (A1 mode) at 2057.0, 2054.6, 2054.9 and 2059.1 cm(-1), respectively. The TEPs for the phosphine ligands in are among the lowest measured, with values close to P(tBu)3 the most donating phosphine measured by Tolman. The cone angles of L(R) measured in are 152, 179, 200 and 207 degrees for R = Me, iPr, iBu and Bz, respectively. The substituted proazaphosphatranes have larger cone angles compared to the analogous trialkyl subsituted monophosphines. Our study demonstrates that while the cone angles have a significant dependence on R, all of the substituted proazaphosphatranes are strong electron donors. Additionally, in order to determine the electronic donor strength of our previously reported multidentate ligand, TPAP, Ni(TPAP)(CO)2 () (TPAP = tris(2-pyridylmethyl)azaphosphatrane) and Ni(L(Me))2(CO)2 () were also synthesized and evaluated in a similar fashion. PMID- 26905921 TI - Prevalence and trends in the childhood dual burden of malnutrition in low- and middle-income countries, 1990-2012. AB - OBJECTIVE: To describe trends in country- and individual-level dual burden of malnutrition in children <5 years, and age-stratified (<2 years, >=2 years) country-level trends, in thirty-six low- and middle-income countries (LMIC). DESIGN: Using repeated cross-sectional nationally representative data, we calculated the prevalence of malnutrition (stunting, wasting, overweight) at each survey wave, annualized rates of prevalence change for each country over time, and trends before and after 2000, for all children <5 years and separately for those =2 years. We examined country- (ratio of stunting to overweight) and individual-level (coexistence of stunting and overweight) dual burden in children <5 years. SETTING: Demographic and Health Surveys from thirty-six LMIC between 1990 and 2012. SUBJECTS: Children <5 years. RESULTS: Overall malnutrition prevalence decreased in children <5 years, driven by stunting decreases. Stunting rates decreased in 78 % of countries, wasting rates decreased in 58 % of countries and overweight rates increased in 36 % of countries. Rates of change differed for children =2 years, with children <2 years experiencing decreases in stunting in fewer countries yet increases in overweight in more countries. Countries with nearly equal prevalences of stunting and overweight in children <5 years increased from 2000 to the final year. Within a country, 0.3-10.9 % of children <5 years were stunted and overweight, and 0.6-37.8 % of stunted children <5 years were overweight. CONCLUSIONS: The dual burden exists in children <5 years on both country and individual levels, indicating a shift is needed in policies and programmes to address both sides of malnutrition. Children <2 years should be identified as a high-risk demographic. PMID- 26905924 TI - Active Sampling Device for Determining Pollutants in Surface and Pore Water - the In Situ Sampler for Biphasic Water Monitoring. AB - We designed and evaluated an active sampling device, using as analytical targets a family of pesticides purported to contribute to honeybee colony collapse disorder. Simultaneous sampling of bulk water and pore water was accomplished using a low-flow, multi-channel pump to deliver water to an array of solid-phase extraction cartridges. Analytes were separated using either liquid or gas chromatography, and analysis was performed using tandem mass spectrometry (MS/MS). Achieved recoveries of fipronil and degradates in water spiked to nominal concentrations of 0.1, 1, and 10 ng/L ranged from 77 +/- 12 to 110 +/- 18%. Method detection limits (MDLs) were as low as 0.040-0.8 ng/L. Extraction and quantitation of total fiproles at a wastewater-receiving wetland yielded concentrations in surface water and pore water ranging from 9.9 +/- 4.6 to 18.1 +/- 4.6 ng/L and 9.1 +/- 3.0 to 12.6 +/- 2.1 ng/L, respectively. Detected concentrations were statistically indistinguishable from those determined by conventional, more laborious techniques (p > 0.2 for the three most abundant fiproles). Aside from offering time-averaged sampling capabilities for two phases simultaneously with picogram-per-liter MDLs, the novel methodology eliminates the need for water and sediment transport via in situ solid phase extraction. PMID- 26905925 TI - Respiratory and Systemic Effects of LASSBio596 Plus Surfactant in Experimental Acute Respiratory Distress Syndrome. AB - BACKGROUND/AIMS: Exogenous surfactant has been proposed as adjunctive therapy for acute respiratory distress syndrome (ARDS), but it is inactivated by different factors present in the alveolar space. We hypothesized that co-administration of LASSBio596, a molecule with significant anti-inflammatory properties, and exogenous surfactant could reduce lung inflammation, thus enabling the surfactant to reduce edema and improve lung function, in experimental ARDS. METHODS: ARDS was induced by cecal ligation and puncture surgery in BALB/c mice. A sham operated group was used as control (CTRL). After surgery (6 hours), CTRL and ARDS animals were assigned to receive: (1) sterile saline solution; (2) LASSBio596; (3) exogenous surfactant or (4) LASSBio596 plus exogenous surfactant (n = 22/group). RESULTS: Regardless of exogenous surfactant administration, LASSBio596 improved survival rate and reduced collagen fiber content, total number of cells and neutrophils in PLF and blood, cell apoptosis, protein content in BALF, and urea and creatinine levels. LASSBio596 plus surfactant yielded all of the aforementioned beneficial effects, as well as increased BALF lipid content and reduced surface tension. CONCLUSION: LASSBio596 exhibited major anti-inflammatory and anti-fibrogenic effects in experimental sepsis-induced ARDS. Its association with surfactant may provide further advantages, potentially by reducing surface tension. PMID- 26905926 TI - The risk of Clostridium difficile associated diarrhea in nasogastric tube insertion: A systematic review and meta-analysis. AB - BACKGROUND/OBJECTIVES: Clostridium difficile-associated diarrhea (CDAD) is a major concern of public health worldwide. The risk of CDAD in patients with nasogastric tube (NGT) insertion is controversial. The aim of this study was to assess the risk of incidence of CDAD in patients with NGT insertion. METHODS: A literature search was performed using MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews from inception through August 2015. Studies that reported relative risks, odds ratios, or hazard ratios comparing the risk of CDAD in patients with NGT insertion versus those who did not were included. Pooled risk ratios (RR) and 95% confidence interval (CI) were calculated using a random effect, generic inverse variance method. RESULTS: Eleven observational studies were included in our analysis to assess the association between NGT insertion and risk of CDAD. The pooled RR of CDAD in patients with NGT insertion was 1.87 (95% CI, 1.06-3.28, I(2)=73). When meta-analysis was limited only to cohort and case control studies, the pooled RR of CDAD was 1.99 (95% CI, 1.05-3.77, I(2)=76). CONCLUSIONS: Our study demonstrated a statistically significant association between NGT insertion and risk of CDAD. This finding may impact clinical management and primary prevention of CDAD. PMID- 26905927 TI - Mutations to the cardiotonic steroid binding site of Na(+)/K(+)-ATPase are associated with high level of resistance to gamabufotalin in a natricine snake. AB - Although toads are defended by bufadienolide toxins, some snakes have evolved resistance to bufadienolides and feed heavily on toads. We compared resistance in Nerodia rhombifer, which possesses mutations that confer target-site resistance, to Pituophis catenifer, which lacks those mutations. Even at the highest dosage tested, Nerodia showed no effects, whereas the lowest dose was lethal to Pituophis. Our results demonstrate a striking level of resistance to bufadienolides in a species possessing the mutations for resistance. PMID- 26905928 TI - Sexual counselling for sexual problems in patients with cardiovascular disease. AB - BACKGROUND: Sexual problems are common among people with cardiovascular disease. Although clinical guidelines recommend sexual counselling for patients and their partners, there is little evidence on its effectiveness. OBJECTIVES: To evaluate the effectiveness of sexual counselling interventions (in comparison to usual care) on sexuality-related outcomes in patients with cardiovascular disease and their partners. SEARCH METHODS: We searched CENTRAL, MEDLINE, EMBASE, and three other databases up to 2 March 2015 and two trials registers up to 3 February 2016. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs, including individual and cluster RCTs. We included studies that compared any intervention to counsel adult cardiac patients about sexual problems with usual care. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included three trials with 381 participants. We were unable to pool the data from the included studies due to the differences in interventions used; therefore we synthesised the trial findings narratively.Two trials were conducted in the USA and one was undertaken in Israel. All trials included participants who were admitted to hospital with myocardial infarction (MI), and one trial also included participants who had undergone coronary artery bypass grafting. All trials followed up participants for a minimum of three months post-intervention; the longest follow-up timepoint was five months.One trial (N = 92) tested an intensive (total five hours) psychotherapeutic sexual counselling intervention delivered by a sexual therapist. One trial (N = 115) used a 15-minute educational video plus written material on resuming sexual activity following a MI. One trial (N = 174) tested the addition of a component that focused on resumption of sexual activity following a MI within a hospital cardiac rehabilitation programme.The quality of the evidence for all outcomes was very low.None of the included studies reported any outcomes from partners.Two trials reported sexual function. One trial compared intervention and control groups on 12 separate sexual function subscales and used a repeated measures analysis of variance (ANOVA) test. They reported statistically significant differences in favour of the intervention. One trial compared intervention and control groups using a repeated measures analysis of covariance (ANCOVA), and concluded: "There were no significant differences between the two groups [for sexual function] at any of the time points".Two trials reported sexual satisfaction. In one trial, the authors compared sexual satisfaction between intervention and control and used a repeated measured ANOVA; they reported "differences were reported in favour of the intervention". One trial compared intervention and control with a repeated measures ANCOVA and reported: "There were no significant differences between the two groups [for sexual satisfaction] at any of the timepoints".All three included trials reported the number of patients returning to sexual activity following MI. One trial found some evidence of an effect of sexual counselling on reported rate of return to sexual activity (yes/no) at four months after completion of the intervention (relative risk (RR) 1.71, 95% confidence interval (CI) 1.26 to 2.32; one trial, 92 participants, very low quality of evidence). Two trials found no evidence of an effect of sexual counselling on rate of return to sexual activity at 12 week (RR 1.01, 95% CI 0.94 to 1.09; one trial, 127 participants, very low quality of evidence) and three month follow-up (RR 0.98, 95% CI 0.88 to 1.10; one trial, 115 participants, very low quality of evidence).Two trials reported psychological well-being. In one trial, no scores were reported, but the trial authors stated: "No treatment effects were observed on state anxiety as measured in three points in time". In the other trial no scores were reported but, based on results of a repeated measures ANCOVA to compare intervention and control groups, the trial authors stated: "The experimental group had significantly greater anxiety at one month post MI". They also reported: "There were no significant differences between the two groups [for anxiety] at any other time points".One trial reporting relationship satisfaction and one trial reporting quality of life found no differences between intervention and control.No trial reported on satisfaction in how sexual issues were addressed in cardiac rehabilitation services. AUTHORS' CONCLUSIONS: We found no high quality evidence to support the effectiveness of sexual counselling for sexual problems in patients with cardiovascular disease. There is a clear need for robust, methodologically rigorous, adequately powered RCTs to test the effectiveness of sexual counselling interventions for people with cardiovascular disease and their partners. PMID- 26905929 TI - Protective role of Interleukin 27 (IL-27) gene polymorphisms in patients with ulcerative colitis. AB - Ulcerative colitis (UC) is a chronic condition of unknown etiology and a polygenic disease. The interleukin 27 (IL-27) have been implicated in the pathogenesis of several autoimmune diseases including inflammatory bowel disease. Several polymorphisms of IL-27 have been associated with several types of cancer and immune disorders. The aim of the present study was to evaluate the association between IL-27 gene polymorphisms and the development of UC. Four polymorphisms of IL-27p28 gene (rs181206, rs26528, rs17855750, and rs40837) and three of the Epstein-Barr virus-induced gene 3 (EBI3) (rs428253, rs4740, and rs4905) were genotyped by 5' exonuclease TaqMan genotyping assays on an ABI Prism 7900HT Fast Real-Time PCR System in 375 Mexican patients with UC and 1599 Mexican Mestizo healthy unrelated individuals. IL-27 levels were determined in 458 healthy controls. Under recessive model adjusted by age and gender, the IL-27p28 rs17855750 polymorphism was associated with decreased risk of developing UC (OR=0.27, 95% CI: 0.06-1.13, P=0.031). On the other hand, under recessive models adjusted by age and gender, the EBI3 rs428253 (OR=0.54, 95% CI: 0.29-0.99, P=0.035), rs4740 (OR=0.60, 95% CI: 0.36-1.01, P=0.046) and rs4905 (OR=0.59, 95% CI: 0.35-1.01, P=0.043) were associated with decreased risk of developing UC. Similar levels of IL-27 were observed among the genotypes of the studied polymorphisms. IL-27 polymorphisms might play a protective role for the development of UC in the Mexican population. PMID- 26905930 TI - Non-cleavable talin rescues defect in the T-cell conjugation of T-cells deficient in the immune adaptor SKAP1. AB - While the cytoskeletal protein talin binds to the beta-chain of LFA-1, the immune cell adaptor SKAP1 (SKAP-55) binds to the alpha-chain of the same integrin via RapL. Whereas calpain protease cleavage of talin is important for LFA-1 activation, it has been unclear whether SKAP1 can alter the function of talin or its associated adaptor RIAM in T-cells. In this paper, we report that Skap1-/- T cells showed a reduction in the translocation of talin and RIAM to the contact interface of T-cells with antigenic beads or dendritic cells (DCs) presenting OVA peptide to OT-1 T-cells. In addition, Skap1-/- T-cells show an altered pattern of talin cleavage, while the expression of a cleavage resistant form of talin (L432G) restored the impaired adhesion of OT1 transgenic Skap1-/- T-cells with DCs. SKAP1 therefore can affect the function of talin in T-cells needed for optimal T-cell/DC conjugation. PMID- 26905931 TI - A peptide immunization approach to counteract a Staphylococcus aureus protease defense against host immunity. AB - Pathogens that induce acute and chronic infections, as well as certain cancers, employ numerous strategies to thwart host cellular and humoral immune defenses. One proposed evasion mechanism against humoral immunity is a localized expression of extracellular proteases that cleave the IgG hinge and disable host IgG functions. Host immunity appears to be prepared to counter such a proteolytic tactic by providing a group of autoantibodies, denoted anti-hinge antibodies that specifically bind to cleaved IgGs and provide compensating functional restoration in vitro. These respective counter-measures highlight the complex interrelationships among pathogens and host immunity and suggested to us a possible means for therapeutic intervention. In this study, we combined an investigation of pathogen-mediated proteolysis of host IgGs with an immunization strategy to boost host anti-hinge antibodies. In a Staphylococcus aureus infection model using an artificial tissue cage (wiffle ball) implanted into rabbits, cleaved rabbit IgGs were detected in abundance in the abscesses of untreated animals early after infection. However, in animals previously immunized with peptide analogs of the cleaved IgG hinge to generate substantial anti-hinge antibody titers, S. aureus colony formation was markedly reduced compared to control animals or those similarly immunized with a scrambled peptide sequence. The results of this study demonstrate that extensive local proteolysis of IgGs occurs in a test abscess setting and that immunization to increase host anti hinge antibodies provided substantial acute protection against bacterial growth. PMID- 26905933 TI - In situ synthesis of 3D CoS nanoflake/Ni(OH)2 nanosheet nanocomposite structure as a candidate supercapacitor electrode. AB - A three-dimensional (3D) CoS/Ni(OH)2 nanocomposite structure based on CoS nanoflakes and two-dimensional (2D) Ni(OH)2 nanosheets were in situ synthesized on Ni foam by a whole hydrothermal reaction and electrodeposition process. The 3D CoS/Ni(OH)2 nanocomposite structures demonstrate the combined advantages of a sustained cycle stability of CoS and high specific capacitance from Ni(OH)2. The obtained CoS/Ni(OH)2 nanocomposite structures on Ni foam can directly serve as a binder-free electrode for a supercapacitor. For the 3D CoS/Ni(OH)2 nanocomposite electrode, the high specific capacitance is 1837 F g(-1) at a scan rate of 1 mV s(-1), which is obviously higher than both the bare CoS electrode and Ni(OH)2 electrode. The galvanostatic charge and discharge measurements illustrate that the 3D CoS/Ni(OH)2 nanocomposite electrode possesses excellent cycle stability, and it keeps a 95.8% retention of the initial capacity after 5000 cycles. Electrochemical impedance spectroscopy measurements also confirm that the 3D CoS/Ni(OH)2 nanocomposite electrode has better electrochemical characteristics. These remarkable performances can be attributed to the unique 3D nanoporous structure of CoS/Ni(OH)2 which leads to a large accessible surface area and a high stability during long-term operation. In addition, 2D Ni(OH)2 nanosheets in 3D nanocomposite structures can afford rapid mass transport and a strong synergistic effect of CoS and Ni(OH)2 as individual compositions contribute to the high performance of the nanocomposite structure electrode. These results may promote the design and implementation of nanocomposite structures in advanced supercapacitors. PMID- 26905932 TI - "The sun has set even though it is morning": Experiences and explanations of perinatal depression in an urban township, Cape Town. AB - This study examined experiences and explanations of depression amongst Xhosa speaking pregnant women, mothers, and health workers in an urban township in Cape Town, South Africa. The study was conducted as part of formative research for a randomised controlled trial to develop and evaluate a task-sharing counselling intervention for maternal depression in this setting. We conducted qualitative semi-structured interviews with 12 depressed and 9 nondepressed pregnant women and mothers of young babies, and 13 health care providers. We employed an in depth framework analysis approach to explore the idioms, descriptions, and perceived causes of depression particular to these women, and compared these with the ICD-10 and DSM-5 criteria for major depression. We found that symptoms of major depression are similar in this township to those described in international criteria (withdrawal, sadness, and poor concentration), but that local descriptions of these symptoms vary. In addition, all the symptoms described by participants were directly related to stressors occurring in the women's lives. These stressors included poverty, unemployment, lack of support from partners, abuse, and death of loved ones, and were exacerbated by unwanted or unplanned pregnancies and the discovery of HIV positive status at antenatal appointments. The study calls attention to the need for specifically designed counselling interventions for perinatal depression that are responsive to the lived experiences of these women and grounded in the broader context of poor socioeconomic conditions and living environments in South Africa, all of which have a direct impact on mental health. PMID- 26905934 TI - Towards "evidence-making intervention" approaches in the social science of implementation science: The making of methadone in East Africa. AB - In this commentary, we take the recent introduction of methadone treatment in response to emerging problems of HIV linked to heroin addiction in Kenya as a case for reflecting on the social science of implementation science. We offer a framework of 'evidence-making intervention' which we hold as distinct from mainstream 'evidence-based intervention' approaches. Whilst accepting that interventions are shaped in their contexts, evidence-based intervention approaches tend to imagine a stable intervention object with universal effect potential. By contrast, an evidence-making intervention approach investigates how an intervention, and the knowledge which constitutes it, is made locally, through its processes of implementation. Drawing on qualitative research generated in Kenya prior to (2012-2013) and during (2014-2015) the implementation of methadone treatment, we explore the making of 'methadone promise' as a case of evidence making intervention. We show how enactments of methadone promise make multiple methadones, through which a binary is negotiated between the narratives of methadone as hope for addiction recovery and methadone as hope for HIV prevention. Addiction recovery narratives predominate, despite methadone's incorporation into policy via its globally supported HIV prevention evidence base. Key practices in the making of methadone promise in Kenya include its medicalization, and renaming, as 'medically assisted treatment' - or simply 'MAT' - which distance it from prior constitutions elsewhere as a drug of substitution, and the visualisation of its effects wherein unhealthy people can be seen and shown to have become well. We also show how actors seek to protect the story of methadone promise from counter narratives, including through mass media projects. We conclude that there is no single biomedical object of methadone intervening on a single biological body across contexts, and no single universe of evidence. By giving weight to local rather than outside expert knowledge, and by tracing how the meaning of intervention is made locally through its implementation, we can make visible the multiple enactments of an intervention and how these shape local ecologies of care, including in ways beyond those foreseen by an intervention's evidencing elsewhere. PMID- 26905935 TI - Near Infrared-Guided Smart Nanocarriers for MicroRNA-Controlled Release of Doxorubicin/siRNA with Intracellular ATP as Fuel. AB - In chemotherapy, it is a great challenge to recruit endogenous stimuli instead of external intervention for targeted delivery and controlled release; microRNAs are the most promising candidates due to their vital role during tumorigenesis and significant expression difference. Herein, to amplify the low abundant microRNAs in live cells, we designed a stimuli-responsive DNA Y-motif for codelivery of siRNA and Dox, in which the cargo release was achieved via enzyme-free cascade amplification with endogenous microRNA as trigger and ATP (or H(+)) as fuel through toehold-mediated strand displacement. Furthermore, to realize controlled release in tumor cells, smart nanocarriers were constructed with stimuli responsive Y-motifs, gold nanorods, and temperature-sensitive polymers, whose surfaces could be reversibly switched between PEG and RGD states via photothermal conversion. The PEG corona kept the nanocarriers stealth during blood circulation to protect the Y-motifs against nuclease digestion and enhance passive accumulation, whereas the exposed RGD shell under near-infrared (NIR) irradiation at tumor sites facilitated the specific receptor-mediated endocytosis by tumor cells. Through modulating NIR laser, microRNA, or ATP expressions, the therapy efficacies to five different cell lines were finely controlled, presenting NIR guided accumulation, massive release, efficient gene silence, and severe apoptosis in HeLa cells; in vivo study showed that a low dosage of nanocarriers synergistically inhibited the tumor growth by silencing gene expression and inducing cell apoptosis under mild NIR irradiation, though they only brought minimum damage to normal organs. The combination of nanomaterials, polymers, and DNA nanomachines provided a promising tool for designing smart nanodevices for disease therapy. PMID- 26905936 TI - Role of EUS evaluation after endoscopic eradication of esophageal varices with band ligation. AB - BACKGROUND AND AIMS: Variceal recurrence after endoscopic band ligation (EBL) for secondary prophylaxis is a frequent event. Some studies have reported a correlation between variceal recurrence and variceal rebleeding with the EUS features of paraesophageal vessels. A prospective observational study was conducted to correlate EUS evaluation of paraesophageal varices, azygos vein, and thoracic duct with variceal recurrence after EBL variceal eradication in patients with cirrhosis. METHODS: EUS was performed before and 1 month after EBL variceal eradication. Paraesophageal varices, azygos vein, and thoracic duct maximum diameters were evaluated in predetermined anatomic stations. After EBL variceal eradication, patients were submitted to endoscopic examinations every 3 months for 1 year. We looked for EUS features that could predict variceal recurrence. RESULTS: Thirty patients completed a 1-year endoscopic follow-up. Seventeen patients (57%) presented variceal recurrence. There was no correlation between azygos vein and thoracic duct diameter with variceal recurrence. Larger paraesophageal varices predicted variceal recurrence in both evaluation periods. Paraesophageal varices diameters that best correlated with variceal recurrence were 6.3 mm before EBL (52.9% sensitivity, 92.3% specificity, and .749 area under the receiver operating characteristic curve [AUROC]) and 4 mm after EBL (70.6% sensitivity, 84.6% specificity, and .801 AUROC). CONCLUSIONS: We conclude that paraesophageal varices diameter measured by EUS predicts variceal recurrence within 1 year after EBL variceal eradication. Paraesophageal diameter after variceal eradication is a better recurrence predictor, because it has a lower cut off parameter, higher sensitivity, and higher AUROC. PMID- 26905937 TI - Management of branch-duct intraductal papillary mucinous neoplasms: a large single-center study to assess predictors of malignancy and long-term outcomes. AB - BACKGROUND AND AIMS: Management of branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) remains challenging. We determined factors associated with malignancy in BD-IPMNs and long-term outcomes. METHODS: This retrospective cohort study included all patients with established BD-IPMNs by the International Consensus Guidelines (ICG) 2012 and/or pathologically confirmed BD-IPMNs in a tertiary care referral center between 2001 and 2013. Main outcome measures were the association between high-risk stigmata (HRS)/worrisome features (WFs) of the ICG 2012 and malignant BD-IPMNs, performance characteristics of EUS-FNA for the diagnosis of malignant BD-IPMNs, and recurrence and long-term outcomes of BD-IPMN patients undergoing surgery or imaging surveillance. RESULTS: Of 364 BD-IPMN patients, 229 underwent imaging surveillance and 135 underwent surgery. Among the 135 resected BD-IPMNs, HRS/WFs on CT/magnetic resonance imaging (MRI) were similar between the benign and malignant groups, but main pancreatic duct (MPD) dilation (5-9 mm) was more frequently identified in malignant lesions. On EUS FNA, mural nodules, MPD features suspicious for involvement, and suspicious/positive malignant cytology were more frequently detected in the malignant group with a sensitivity, specificity, and accuracy of 33%, 94%, and 86%; 42%, 91%, and 83%; and 33% 91%, and 82%, respectively. Mural nodules identified by EUS were missed by CT/MRI in 28% in the malignant group. Patients with malignant lesions had a higher risk of any IPMN recurrence during a mean follow-up period of 131 months (P = .01). CONCLUSIONS: Among HRS and WFs of the ICG 2012, an MPD size of 5 to 9 mm on CT/MRI was associated with malignant BD IPMNs. EUS features including mural nodules, MPD features suspicious for involvement, and suspicious/malignant cytology were accurate and highly specific for malignant BD-IPMNs. Our study highlights the incremental value of EUS-FNA over imaging in identifying malignant BD-IPMNs, particularly in patients without WFs and those with smaller cysts. Benign IPMN recurrence was observed in some patients up to 8 years after resection. PMID- 26905938 TI - Patient safety during sedation by anesthesia professionals during routine upper endoscopy and colonoscopy: an analysis of 1.38 million procedures. AB - BACKGROUND AND AIMS: Sedation for GI endoscopy directed by anesthesia professionals (ADS) is used with the intention of improving throughput and patient satisfaction. However, data on its safety are sparse because of the lack of adequately powered, randomized controlled trials comparing it with endoscopist directed sedation (EDS). This study was intended to determine whether ADS provides a safety advantage when compared with EDS for EGD and colonoscopy. METHODS: This retrospective, nonrandomized, observational cohort study used the Clinical Outcomes Research Initiative National Endoscopic Database, a network of 84 sites in the United States composed of academic, community, health maintenance organization, military, and Veterans Affairs practices. Serious adverse events (SAEs) were defined as any event requiring administration of cardiopulmonary resuscitation, hospital or emergency department admission, administration of rescue/reversal medication, emergency surgery, procedure termination because of an adverse event, intraprocedural adverse events requiring intervention, or blood transfusion. RESULTS: There were 1,388,235 patients in this study that included 880,182 colonoscopy procedures (21% ADS) and 508,053 EGD procedures (23% ADS) between 2002 and 2013. When compared with EDS, the propensity-adjusted SAE risk for patients receiving ADS was similar for colonoscopy (OR, .93; 95% CI, .82 1.06) but higher for EGD (OR, 1.33; 95% CI, 1.18-1.50). Additionally, with further stratification by American Society of Anesthesiologists (ASA) class, the use of ADS was associated with a higher SAE risk for ASA I/II and ASA III subjects undergoing EGD and showed no difference for either group undergoing colonoscopy. The sample size was not sufficient to make a conclusion regarding ASA IV/V patients. CONCLUSIONS: Within the confines of the SAE definitions used, use of anesthesia professionals does not appear to bring a safety benefit to patients receiving colonoscopy and is associated with an increased SAE risk for ASA I, II, and III patients undergoing EGD. PMID- 26905940 TI - Neuropsychological assessment in different King's clinical stages of amyotrophic lateral sclerosis. AB - Emerging evidence shows that cognitive deficits associated with frontal lobe dysfunction occur from early stages of amyotrophic lateral sclerosis (ALS). We aimed to assess neuropsychological functioning at different stages of ALS to further delineate the occurrence of cognitive impairment alongside the trajectory of ALS as defined by standard assessment procedures. We investigated several cognitive domains in 74 ALS patients classified into four different clinical stages of disease, according to a recently validated staging system for ALS (known as 'King's' system), and evaluated and compared the corresponding cognitive profiles. We found that data derived from global cognitive assessment and several executive (i.e. Frontal Assessment Battery and Trail Making Test B-A) and long-term memory (i.e. memory prose) tests were significantly different among the subsets of ALS patients, showing poorer performances with increasing clinical disability. In conclusion, our preliminary results support the notion that mainly frontotemporal abilities may be impaired during the ALS course and suggest that neuropsychological information could supplement the current clinical staging of patients. However, ALS-specific multi-domain screening instruments, which allow to correct neuropsychological scores for physical disability, should be validated in larger populations worldwide and routinely introduced in clinical practice. PMID- 26905939 TI - Carbonate-based Janus micromotors moving in ultra-light acidic environment generated by HeLa cells in situ. AB - Novel approaches to develop naturally-induced drug delivery in tumor environments in a deterministic and controlled manner have become of growing interest in recent years. Different polymeric-based microstructures and other biocompatible substances have been studied taking advantage of lactic acidosis phenomena in tumor cells, which decrease the tumor extracellular pH down to 6.8. Micromotors have recently demonstrated a high performance in living systems, revealing autonomous movement in the acidic environment of the stomach or moving inside living cells by using acoustic waves, opening the doors for implementation of such smart microengines into living entities. The need to develop biocompatible motors which are driven by natural fuel sources inherently created in biological systems has thus become of crucial importance. As a proof of principle, we here demonstrate calcium carbonate Janus particles moving in extremely light acidic environments (pH 6.5), whose motion is induced in conditioned acidic medium generated by HeLa cells in situ. Our system not only obviates the need for an external fuel, but also presents a selective activation of the micromotors which promotes their motion and consequent dissolution in presence of a quickly propagating cell source (i.e. tumor cells), therefore inspiring new micromotor configurations for potential drug delivery systems. PMID- 26905941 TI - Correction to Manganese Doping of Monolayer MoS2: The Substrate Is Critical. PMID- 26905947 TI - The self-absorption correction factors for 210Pb concentration in mining waste and influence on environmental radiation risk assessment. AB - The radioactive lead isotope 210Pb occurs in waste originating from metal smelting and refining industry, gas and oil extraction and sometimes from underground coal mines, which are deposited in natural environment very often. Radiation risk assessment requires accurate knowledge about the concentration of 210Pb in such materials. Laboratory measurements seem to be the only reliable method applicable in environmental 210Pb monitoring. One of the methods is gamma ray spectrometry, which is a very fast and cost-effective method to determine 210Pb concentration. On the other hand, the self-attenuation of gamma ray from 210Pb (46.5 keV) in a sample is significant as it does not depend only on sample density but also on sample chemical composition (sample matrix). This phenomenon is responsible for the under-estimation of the 210Pb activity concentration level often when gamma spectrometry is applied with no regard to relevant corrections. Finally, the corresponding radiation risk can be also improperly evaluated. Sixty samples of coal mining solid tailings (sediments created from underground mining water) were analysed. Slightly modified and adapted to the existing laboratory condition, a transmission method has been applied for the accurate measurement of 210Pb concentration . The observed concentrations of 210Pb range between 42.2 / 11,700 Bq.kg-1 of dry mass. Experimentally obtained correction factors related to a sample density and elemental composition range between 1.11 and 6.97. Neglecting this factor can cause a significant error or underestimations in radiological risk assessment. The obtained results have been used for environmental radiation risk assessment performed by use of the ERICA tool assuming exposure conditions typical for the final destination of such kind of waste. PMID- 26905942 TI - An Endothelial Hsp70-TLR4 Axis Limits Nox3 Expression and Protects Against Oxidant Injury in Lungs. AB - AIMS: Oxidants play a critical role in the pathogenesis of acute lung injury (ALI). Nox3 is a novel member of the NADPH oxidase (Nox) family of oxidant generating enzymes, which our laboratory had previously identified to be induced in the lungs of TLR4(-/-) mice. However, the physiologic role of Nox3 induction in lungs and its precise relationship to TLR4 are unknown. Furthermore, the cell compartment involved and the signaling mechanisms of Nox3 induction are unknown. RESULTS: We identified that Nox3 is regulated by heat shock protein 70 (Hsp70) signaling via a TLR4-Trif-signal transducer and activator of transcription 3 (Stat3) pathway and that Nox3 induction leads to increased oxidant injury and death in mice and lung endothelial cells. We generated Nox3(-/-)/TLR4(-/-) double knockout mice, endothelial-targeting lentiviral silencing constructs, and endothelial-targeted Stat3(-/-) mice to specifically demonstrate that Nox3 induction is responsible for the pro-oxidant, proapoptotic phenotype of TLR4(-/-) mice. We also show that an endothelial Hsp70-TLR4-Trif-Stat3 axis is required to suppress deleterious Nox3 induction. INNOVATION: To date, a physiologic role for Nox3 in oxidant-induced ALI has not been identified. In addition, we generated unique double knockout mice and endothelial-targeted lentiviral silencing constructs to specifically demonstrate the role of a TLR4 signaling pathway in regulating pro-oxidant generation. CONCLUSIONS: We identified an endothelial TLR4 Trif antioxidant pathway that leads to the inhibition of a novel NADPH oxidase, Nox3, in lungs and lung endothelial cells. We also identified the role of a TLR4 ligand, Hsp70, in suppressing Nox3 in basal and pro-oxidant conditions. These studies identify potentially new therapeutic targets in oxidant-induced ALI. Antioxid. Redox Signal. 24, 991-1012. PMID- 26905948 TI - Laparoscopic implantation of artificial urinary sphincter: An option for treating recurrent female urinary incontinence. AB - INTRODUCTION: The failure rate for anti-incontinence surgery ranges from 5% to 80%. There is not actual consensus on the use of artificial urinary sphincter (AUS) as treatment for recurrent urinary incontinence in women. Several authors have shown that AUS can be useful, if the intrinsic sphincteric deficiency is checked. We present the first case in Spain, to our knowledge, of laparoscopic implantation of AUS as treatment for female recurrent urinary incontinence. MATERIAL AND METHODS: Under general anaesthesia, patient was placed in supine decubitus with slight Trendelenburg, access to the vagina was verified. Through a transperitoneal pelvic laparoscopic approach, Retzius space was opened and then the laterovaginal spaces up to the endopelvic fascia. To facilitate the dissection of the bladder neck, we inserted a swab into the vagina, performing simultaneous traction and countertraction manoeuvres. As an access port for the AUS, we widened the incision of the lower trocar. We adjusted the periurethral cuff and then placed the reservoir and the pump in the laterovesical space and the labia majora of the vulva, respectively. Lastly, we connected the 3 AUS elements and peritoneum was closed to isolate AUS from the intestine. RESULTS: The surgical time was 92min, the estimated blood loss was <100cc(3) and the hospital stay was 48h. There were no intraoperative or postoperative complications. The AUS was activated at 6 weeks. At 24 months, patient managed the AUS adequately and total continence was achieved. CONCLUSIONS: Laparoscopic implantation of AUS is a feasible technique. Transvaginal traction and countertraction manoeuvres can prevent intraoperative lesions. PMID- 26905949 TI - Disease-related mortality exceeds treatment-related mortality in patients with chronic myeloid leukemia on second-line or later therapy. AB - Treatment of newly-diagnosed patients with chronic-phase chronic myeloid leukemia (CP-CML) with tyrosine kinase inhibitors (TKIs) results in near-normal life expectancy. However, CP-CML patients resistant to initial TKIs face a poorer prognosis and significantly higher CML-related mortality. We conducted a systematic literature review to evaluate the specific causes of deaths (diseases progression versus drug-related) in CP-CML patients receiving second- or third line therapy. We identified eight studies based on our criteria that reported causes of death. Overall, 5% of second-line and 10% of third-line patients died during the study follow-up period. For second-line, (7 studies, n=1926), mortality was attributed to disease progression for 41% of deaths, 2% to treatment-related causes, 3% were treatment-unrelated, and 50% were unspecified adverse events (AEs), not likely related to study drug. In third-line, (2 studies, n=144), 71% deaths were attributed to disease progression, 7% treatment related AEs, 14% treatment-unrelated and 7% unspecified AEs. Annual death rates for second- and third-line therapy were significantly higher than for general population in similar age group. Our findings suggest death attributed to disease progression is approximately 10 times that due to treatment-related AEs in patients with CP-CML receiving second- or third-line therapy. Therefore, the potential benefits of effective treatment for these patients with the currently available TKIs outweigh the risks of treatment-induced AEs. PMID- 26905951 TI - Neuroprotection by caffeine in the MPTP model of parkinson's disease and its dependence on adenosine A2A receptors. AB - Considerable epidemiological and laboratory data have suggested that caffeine, a nonselective adenosine receptor antagonist, may protect against the underlying neurodegeneration of parkinson's disease (PD). Although both caffeine and more specific antagonists of the A2A subtype of adenosine receptor (A2AR) have been found to confer protection in animal models of PD, the dependence of caffeine's neuroprotective effects on the A2AR is not known. To definitively determine its A2AR dependence, the effect of caffeine on 1-methyl-4-phenyl-1,2,3,6 tetra hydropyridine (MPTP) neurotoxicity was compared in wild-type (WT) and A2AR gene global knockout (A2A KO) mice, as well as in central nervous system (CNS) cell type-specific (conditional) A2AR knockout (cKO) mice that lack the receptor either in postnatal forebrain neurons or in astrocytes. In WT and in heterozygous A2AR KO mice caffeine pretreatment (25mg/kgip) significantly attenuated MPTP induced depletion of striatal dopamine. By contrast in homozygous A2AR global KO mice caffeine had no effect on MPTP toxicity. In forebrain neuron A2AR cKO mice, caffeine lost its locomotor stimulant effect, whereas its neuroprotective effect was mostly preserved. In astrocytic A2AR cKO mice, both caffeine's locomotor stimulant and protective properties were undiminished. Taken together, these results indicate that neuroprotection by caffeine in the MPTP model of PD relies on the A2AR, although the specific cellular localization of these receptors remains to be determined. PMID- 26905952 TI - Proprioceptive acuity predicts muscle co-contraction of the tibialis anterior and gastrocnemius medialis in older adults' dynamic postural control. AB - Older adults use a different muscle strategy to cope with postural instability, in which they 'co-contract' the muscles around the ankle joint. It has been suggested that this is a compensatory response to age-related proprioceptive decline however this view has never been assessed directly. The current study investigated the association between proprioceptive acuity and muscle co contraction in older adults. We compared muscle activity, by recording surface electromyography (EMG) from the bilateral tibialis anterior (TA) and gastrocnemius medialis (GM) muscles, in young (aged 18-34) and older adults (aged 65-82) during postural assessment on a fixed and sway-referenced surface at age equivalent levels of sway. We performed correlations between muscle activity and proprioceptive acuity, which was assessed using an active contralateral matching task. Despite successfully inducing similar levels of sway in the two age groups, older adults still showed higher muscle co-contraction. A stepwise regression analysis showed that proprioceptive acuity measured using variable error was the best predictor of muscle co-contraction in older adults. However, despite suggestions from previous research, proprioceptive error and muscle co contraction were negatively correlated in older adults, suggesting that better proprioceptive acuity predicts more co-contraction. Overall, these results suggest that although muscle co-contraction may be an age-specific strategy used by older adults, it is not to compensate for age-related proprioceptive deficits. PMID- 26905953 TI - Ultrasonographic evaluation of the femoral cartilage thickness in patients with chronic renal failure. AB - OBJECTIVE: To investigate the effects of chronic renal failure (CRF) on the distal femoral cartilage thickness by using ultrasonography and to determine the relationship between cartilage thickness and certain disease-related parameters. DESIGN: Fifty-seven CRF patients (41 male and 16 female) (mean [SD] age, 44.7 [12.1] years) and 60 healthy controls (41 male and 19 female) (mean [SD] age, 43.5 [13.3] years) were enrolled in this study. Demographic and clinical characteristics were recorded. Cartilage thickness measurements were taken from the medial and lateral condyles, and intercondylar areas of both knees. RESULTS: Groups were similar in terms of age, weight, height, body mass index and gender (all p>0.05). The mean cartilage thickness was found to be less in CRF patients than in controls (statistically significant for medial condyles and intercondylar areas both in right and the left knees [all p<0.05]). Cartilage thickness showed no correlation with eGFR, and with the levels of serum urea, creatinine, calcium, magnesium, phosphor, hemoglobin, uric acid and as well as steroid use (all p>0.05) in CRF patients. CONCLUSION: In the light of our findings, we imply that patients with CRF have thinner femoral cartilage than healthy controls. This result may support the view that patients with CRF are at increased risk for developing early knee osteoarthritis. Last but not least, clinicians should be aware of the importance of rehabilitation strategies aimed at decreasing onset and progression of knee osteoarthritis in patients with CRF. PMID- 26905950 TI - Developmental changes in serotonin signaling: Implications for early brain function, behavior and adaptation. AB - The neurotransmitter serotonin (5-HT) plays a central role in brain development, regulation of mood, stress reactivity and risk of psychiatric disorders, and thus alterations in 5-HT signaling early in life have critical implications for behavior and mental health across the life span. Drawing on preclinical and emerging human evidence this narrative review paper will examine three key aspects when considering the consequences of early life changes in 5-HT: (1) developmental origins of variations of 5-HT signaling; (2) influence of genetic and epigenetic factors; and (3) preclinical and clinical consequences of 5-HT related changes associated with antidepressant exposure (SSRIs). The developmental consequences of altered prenatal 5-HT signaling varies greatly and outcomes depend on an ongoing interplay between biological (genetic/epigenetic variations) and environmental factors, both pre and postnatally. Emerging evidence suggests that variations in 5-HT signaling may increase sensitivity to risky home environments, but may also amplify a positive response to a nurturing environment. In this sense, factors that change central 5-HT levels may act as 'plasticity' rather than 'risk' factors associated with developmental vulnerability. Understanding the impact of early changes in 5-HT levels offers critical insights that might explain the variations in early typical brain development that underlies behavioral risk. PMID- 26905954 TI - MYB-related transcription factors function as regulators of the circadian clock and anthocyanin biosynthesis in Arabidopsis. AB - In Arabidopsis, the MYB (myeloblastosis) gene family contains more than 190 members, which play a number of roles in plant growth and development. Based on their protein structure, this gene family was divided into several subclasses, including the MYB-related class. Currently, an MYB-related gene designated as MYB like Domain (AtMYBD) has been shown to function as a positive regulator of anthocyanin biosynthesis in Arabidopsis. This gene was found to belong to the CCA1-like (circadian clock-associated 1) group, which represents several genes that are master regulators of the circadian clocks of plants. Here, we speculate that AtMYBD is able to regulate anthocyanin biosynthesis in Arabidopsis thaliana in a circadian clock-related manner. PMID- 26905955 TI - Anticataractogenesis Mechanisms of Curcumin and a Comparison of Its Degradation Products: An in Vitro Study. AB - Curcumin (Cur) exhibits anticataractogenesis activity. This study aimed to compare the activities of Cur with those of its degradation products in a series of in vitro lens protein turbidity assays. The results show that Cur (200 MUM) ameliorates selenite-induced crystallin aggregation, and the mean OD value was 0.10 +/- 0.02 (p < 0.05), which was significantly different from controls (0.15 +/- 0.01) after incubating for 3 days. However, Cur did not significantly inhibit calcium-induced proteolysis after incubating for 3 days. Such results were supported by isothermal titration calorimetry observation that Cur binds with selenite but not with calcium. Presence of Cur and the degradation products examined (ferulic acid, cinnamic acid, vanillin, and vanillic acid) indicates significantly protective activities on lens gamma-crystallins after UVC exposure for 3 h. Among the compounds examined, only ferulic acid exhibited a significant inhibitory effect against UVB-induced turbidity with a mean OD of 0.32 +/- 0.01 (p < 0.05), which was significantly different from controls (0.49 +/- 0.02). The previously reported anticataract effects of Cur may stem not only from Cur but also from its degradation products through various cataractogenesis mechanisms in vitro. PMID- 26905956 TI - Short-term effects of a peer co-led educational programme delivered before mental health treatment: A randomised controlled trial. AB - OBJECTIVE: To investigate the 1-month effects of an educational programme co-led by peers delivered before treatment on treatment preferences, self-management knowledge and motivation in comparison to usual care. METHODS: Adults referred to a community mental health centre were randomised to either a control group (n=48) or a peer co-led educational programme (intervention group, n=45). The programme consisted of an 8-hour group education session followed by an individual pretreatment planning session. The main topics of the educational programme were treatment options, patients' rights, self-management, the importance of patient activation and participation. RESULTS: At 1-month follow-up, a significantly larger proportion of the patients in the intervention group knew which type of treatment they preferred (76.7% vs. 32.5%, p<0.001). The intervention group had significantly higher self-management knowledge (p<0.001). There was no effect on treatment motivation (p=0.543). CONCLUSION: At 1-month following the delivery of a pretreatment educational programme, we found that participants' knowledge of treatment preferences and self-management had improved. PRACTICE IMPLICATIONS: Educational interventions co-led by peers can optimise the process of informing and educating outpatients, thereby helping patients to clarify their treatment preferences. PMID- 26905958 TI - Calculations of PAH anions: When are diffuse functions necessary? AB - The effect of including vs. excluding diffuse functions while calculating numerous parameters of PAH anions by various calculation methods is discussed. The omission of diffuse functions appears to have a negligible effect while calculating geometry parameters or total energy; thus, acceptable results may be obtained without them. The conclusions for charge density appear to be the same; however, limited results make an unambiguous claim unachievable. Calculating (1)H and (13)C-NMR shifts undoubtedly requires the use of these functions. PMID- 26905957 TI - Hepatitis B virus full-length genomic mutations and quasispecies in hepatocellular carcinoma. AB - BACKGROUND AND AIM: Hepatitis B virus (HBV) full-length genomic mutations and quasispecies characteristics in hepatocellular carcinoma (HCC) were investigated. METHODS: Hepatitis B virus DNA was extracted from the tumor and non-tumor tissues of 16 HCC patients. Overlapping DNA fragments covering the entire HBV genome were amplified and sequenced. To study HBV sequence at the quasispecies level, the preS region was amplified and clonally sequenced. HBV mutation profiles, quasispecies complexity and diversity, and phylogenetic characteristics were assessed. RESULTS: Fourteen patients had full-length HBV amplification. Hot-spot mutations at HBx aa130-131 and pre-S deletions were detected in 13 (93%) and 6 (43%) patients, respectively. Deletions in the X/preC/C regions were more frequently detected in the tumor than in the non-tumor tissues (P = 0.031). Compared with the non-tumor tissues, the tumor tissues had a lower quasispecies complexity (P = 0.014 and 0.043, at the nucleotide and amino acid levels, respectively) and diversity (P = 0.048 and 0.022, at the nucleotide and amino acid levels, respectively). Phylogenetic analysis showed that HBV sequences derived from tumor and non-tumor tissues were separately clustered, suggesting the occurrence of compartmentalization, which was confirmed by the correlation coefficient testing on both the number and length of branches of viral populations (all P < 0.02). CONCLUSIONS: Hepatitis B virus mutation patterns in HCC tumor tissues and non-tumor tissues were different. HBV quasispecies within the preS region were compartmentalized, and tumor tissues had a lower genome complexity and diversity. Our study suggests HBV evolution is conditioned by the differential host cellular environment in HCC tumors. PMID- 26905959 TI - Resuscitation with Valproic Acid Alters Inflammatory Genes in a Porcine Model of Combined Traumatic Brain Injury and Hemorrhagic Shock. AB - Traumatic brain injury and hemorrhagic shock (TBI+HS) elicit a complex inflammatory response that contributes to secondary brain injury. There is currently no proven pharmacologic treatment for TBI+HS, but modulation of the epigenome has been shown to be a promising strategy. The aim of this study was to investigate whether valproic acid (VPA), a histone deacetylase inhibitor, modulates the expression of cerebral inflammatory gene profiles in a large animal model of TBI+HS. Ten Yorkshire swine were subjected to computer-controlled TBI+HS (40% blood volume). After 2 h of shock, animals were resuscitated with Hextend (HEX) or HEX+VPA (300 mg/kg, n = 5/group). Six hours after resuscitation, brains were harvested, RNA was isolated, and gene expression profiles were measured using a porcine microarray. Ingenuity Pathway Analysis(r) (IPA), gene ontology (GO), Parametric Gene Set Enrichment Analysis (PGSEA), and DAVID (Database for Annotation, Visualization, and Integrated Discovery) were used for pathway analysis. Key microarray findings were verified using real-time polymerase chain reaction (PCR). IPA analysis revealed that VPA significantly down-regulated the complement system (p < 0.001), natural killer cell communication (p < 0.001), and dendritic cell maturation (p < 0.001). DAVID analysis indicated that a cluster of inflammatory pathways held the highest rank and gene enrichment score. Real-time PCR data confirmed that VPA significantly down-expressed genes that ultimately regulate nuclear factor-kB (NF-kB)-mediated production of cytokines, such as TYROBP, TREM2, CCR1, and IL-1beta. This high-throughput analysis of cerebral gene expression shows that addition of VPA to the resuscitation protocol significantly modulates the expression of inflammatory pathways in a clinically realistic model of TBI+HS. PMID- 26905960 TI - Lymph node fine-needle aspiration washout thyroglobulin in papillary thyroid cancer: Diagnostic value and the effect of thyroglobulin antibodies. AB - PURPOSE: Thyroglobulin (Tg) assessment in the needle washout after fine-needle aspiration biopsy (FNAB) of a suspicious neck lymph node (LN) is known to improve the diagnostic accuracy in patients with papillary thyroid cancer (PTC). However, there is still controversy on the best diagnostic cut-off levels for FNAB-Tg and whether thyroglobulin antibody (TgAb) positivity affects FNAB-Tg. The objectives of this study were to determine (i) the diagnostic power of different cut-offs for FNAB-Tg and (ii) if serum TgAb(+) negatively affects the FNAB-Tg evaluation. METHODS: This was a retrospective cohort study analyzing PTC patients with suspicious neck LNs, in a university hospital setting, from October 2009 to October 2013. In total, 103 patients with PTC (226 LNs) undergoing ultrasound guided FNAB for LNs were included. Cytology and FNAB-Tg levels were compared in reference to LN histopathology and the effect of TgAb(+) on FNAB-Tg levels was evaluated. RESULTS: The diagnostic accuracies of FNAB-Tg cut-off of 1 and 10 ng/mL were 94.1% and 88.2%, respectively. Raising the cut-off from 1 to 10 ng/mL led to decreased sensitivity rates (91.9% vs. 83.9%). The receiver operating characteristic curve analysis demonstrated that the best FNAB-Tg cut-off was 1.2 ng/mL. There were no LNs with an FNAB-Tg >= 10 ng/mL that turned out to be cytologically or histopathologically benign. FNAB-Tg levels of the histopathologically malignant LNs were similar between TgAb (+) and TgAb (-) patients (p = 0.546). Serum Tg predicted FNAB-Tg levels above 1 ng/mL (p = 0.002) and FNAB-Tg predicted malignant histopathology (p = 0.004), both independently of the TgAb status of the patient. CONCLUSIONS: FNAB-Tg >= 1 ng/mL has a superior diagnostic power, irrespective of TgAb (+), in PTC patients with suspected LN involvement. PMID- 26905961 TI - Ab Initio Prediction and Characterization of Mo2C Monolayer as Anodes for Lithium Ion and Sodium-Ion Batteries. AB - Identifying suitable electrodes materials with desirable electrochemical properties is urgently needed for the next generation of renewable energy technologies. Here we report an ideal candidate material, Mo2C monolayer, with not only required large capacity but also high stability and mobility by means of first-principles calculations. After ensuring its dynamical and thermal stabilities, various low energy Li and Na adsorption sites are identified, and the electric conductivity of the host material is also maintained. The calculated minor diffusion barriers imply a high mobility and cycling ability of Mo2C. In addition, the Li-adsorbed Mo2C monolayer possesses a high theoretical capacity of 526 mAh.g(-1) and a low average electrode potential of 0.14 eV. Besides, we find that the relatively low capability of Na-adsorbed Mo2C (132 mAh.g(-1)) arises from the proposed competition mechanism. These results highlight the promise of Mo2C monolayer as an appealing anode material for both lithium-ion and sodium-ion batteries. PMID- 26905962 TI - Local Maps of the Polarization and Depolarization in Organic Ferroelectric Field Effect Transistors. AB - We study the local ferroelectric polarization and depolarization of poly(vinylidene fluoride-co-trifluoroethylene) (P(VDF-TrFE)) in p-type ferroelectric field-effect transistors (FeFETs). Piezoresponse force microscopy (PFM) is used to obtain local maps of the polarization on model metal semiconductor-ferroelectric stacks, and on FeFETs stripped from their top-gate electrode; transfer curves are measured on complete FeFETs. The influence of the semiconductor layer thickness and of the polarity and amplitude of the poling voltage are investigated. In accumulation, the stable "on" state consists of a uniform upward-polarized ferroelectric layer, with compensation holes accumulating at the ferroelectric/semiconducting interface. In depletion, the stable "off" state consists of a depolarized region in the center of the transistor channel, surrounded by partially downward-polarized regions over the source and drain electrodes and neighboring regions. The partial depolarization of these regions is due to the incomplete screening of polarization charges by the charges of the remote electrodes. Therefore, thinner semiconducting layers provide higher downward polarizations, which result in a more depleted transistor channel and a higher charge injection barrier between the electrodes and the semiconductor, leading to lower threshold voltages and higher on/off current values at zero gate bias. Clues for optimization of the devices are finally provided. PMID- 26905963 TI - Intravesical radiofrequency-induced hyperthermia combined with chemotherapy for non-muscle-invasive bladder cancer. AB - Although many treatment modalities and schedules for non-muscle-invasive bladder cancer (NMIBC) exist, all yet prove to have limitations. Therefore the search for new forms of therapy continues. One of these forms consists of combining intravesical chemotherapy, typically mitomycin C (MMC), with hyperthermia achieved by a microwave-applicator. We aimed to review the current status of intravesical radiofrequency (RF) induced chemohyperthermia (CHT) for NMIBC with regard to efficacy, adverse-events (AEs) and its future perspective. A search for RF-induced CHT in MEDLINE, Embase, Cochrane and ClinicalTrials.gov databases was performed. Relevant conference abstracts were searched for manually. If applicable, experts on the area were consulted. Papers were selected based on abstract and title. A table of newly published clinical trials since 2011 was constructed. No meta-analysis could be performed based on these new papers. Efficacy proved to be better for RF-induced CHT compared to both MMC alone and bacillus Calmette-Guerin (BCG) instillations, with the latter being based on just one abstract of a randomised controlled trial. The AE rate in CHT is higher compared to MMC instillation, but is similar compared to BCG, albeit different in the type of AE. In almost all studies no severe AEs are reported. Although heterogeneity in methodology exists, RF-induced CHT seems promising. However, alternative methods of applying hyperthermia are starting to present their first results, imposing as effective options too. Intravesical RF-induced CHT may become an alternative for BCG instillation, and possibly for cystectomy, although further level 1 evidence is required for both reliable and reproducible data on efficacy and adverse events. PMID- 26905965 TI - Expression of Concern: Sirtuin-3 deacetylation of cyclophilin D induces dissociation of hexokinase II from the mitochondria. Nataly Shulga, Robin Wilson Smith, John G. Pastorino. J Cell Sci doi: 10.1242/jcs.061846. PMID- 26905966 TI - Expression of Concern: Ethanol sensitizes mitochondria to the permeability transition by inhibiting deacetylation of cyclophilin-D mediated by sirtuin-3. Nataly Shulga, John G. Pastorino. J Cell Sci doi: 10.1242/jcs.073502. PMID- 26905967 TI - Expression of Concern: GRIM-19-mediated translocation of STAT3 to mitochondria is necessary for TNF-induced necroptosis. Nataly Shulga, John G. Pastorino. J Cell Sci doi: 10.1242/jcs.103093. PMID- 26905968 TI - Expression of Concern: Sirtuin-3 modulates Bak- and Bax-dependent apoptosis. Manish Verma, Nataly Shulga, John G. Pastorino. J Cell Sci doi: 10.1242/jcs.115188. PMID- 26905969 TI - Expression of Concern: Mitoneet mediates TNFalpha-induced necroptosis promoted by exposure to fructose and ethanol. Nataly Shulga, John G. Pastorino. J Cell Sci doi: 10.1242/jcs.140764. PMID- 26905970 TI - Wnt controls the transcriptional activity of Kaiso through CK1epsilon-dependent phosphorylation of p120-catenin. PMID- 26905971 TI - Moving forward with dignity: Exploring health awareness in an isolated Deaf community of Australia. AB - BACKGROUND: Those within the Deaf community are disadvantaged in a number of aspects of day-to-day life including their access to health care. At times, they may encounter barriers to health care even before they reach the consultation room. As a consequence, they may receive insufficient and inappropriate health care which may lead to poorer health outcomes. OBJECTIVE: A study was conducted to explore health awareness and access to health information and services of Deaf people living in Tasmania, Australia and identify ways of enhancing the interaction between the Deaf and the wider community. METHODS: A questionnaire was administered, including a number of demographic, health awareness and health service usage questions. In addition, semi-structured interviews and focus groups were conducted with service providers and the Deaf community between March and August 2014. An interpreter was present to translate the questions into Auslan and who then translated the Deaf participant's discussion into English for the researcher. Data were then analyzed using research software SPSS v20.0 and NVivo 10.0. RESULTS: Health as a concept was poorly understood, including mental health, sexual health and health concerning alcohol and drug abuse. Regarding health care resources, due to a sense of security, trust and confidence, the family physician or general practitioner was the single most important health care provider among the Deaf. CONCLUSIONS: The Deaf remain underserved by the current health care system; however, through resourcefulness and life experiences, the Deaf have developed coping and management strategies to move forward with dignity in education, meaningful employment and health access. PMID- 26905972 TI - Accuracy of the FitBit at walking speeds and cadences relevant to clinical rehabilitation populations. AB - BACKGROUND: Activity monitoring is used for motivation and assessing patients in the rehabilitation setting. Monitors available on the market have not been assessed for accuracy at walking patterns seen in the clinical setting. OBJECTIVES: To assess the accuracy of the Fitbit Zip device at different anatomical locations at walking speeds, step length, and cadence similar to those seen in clinical rehabilitation populations. METHODS: Ten healthy participants completed 3 sets of 12 combinations of speed and cadence ranging from 0.2 m/s at 48 steps per minute to 1.0 m/s at 120 steps per minute along a 20 m walkway. Step length was controlled by ground markings and cadence was controlled by a metronome. Five Fitbit Zip devices were concurrently worn at the chest, hip, shin, ankle and forefoot. Percent accuracy for each location and walking condition combination were calculated. RESULTS: At the chest and hip the Fitbit has poor accuracy below 0.7 m/s, however when worn distally, can be accurate to 5.5% at speeds as slow as 0.5 m/s. CONCLUSIONS: For patient populations with slow walking speed, activity monitoring with the Fitbit can be achieved provided the device is located distally on the lower limb. PMID- 26905973 TI - Risk factors for disability discharge in enlisted active duty Army soldiers. AB - BACKGROUND: The rate of permanent disability retirement in U.S. Army soldiers and the prevalence of combat-related disabilities have significantly increased over time. Prior research on risk factors associated with disability retirement included soldiers retired prior to conflicts in Iraq and Afghanistan. OBJECTIVE: To identify risk factors for disability discharge among soldiers enlisted in the U.S. Army during military operations in Iraq and Afghanistan. METHODS: In this case-control study, cases included active duty soldiers evaluated for disability discharge. Controls, randomly selected from soldiers with no history of disability evaluation, were matched to cases based on enlistment year and sex. Conditional logistic regression models calculated odds of disability discharge. Attributable fractions estimated burden of disability for specific pre-existing condition categories. Poisson regression models compared risk of disability discharge related to common disability types by deployment and combat status. RESULTS: Characteristics at military enlistment with increased odds of disability discharge included a pre-existing condition, increased age or body mass index, white race, and being divorced. Musculoskeletal conditions and overweight contributed the largest proportion of disabilities. Deployment was protective against disability discharge or receiving a musculoskeletal-related disability, but significantly increased the risk of disability related to a psychiatric or neurological condition. CONCLUSIONS: Soldiers with a pre-existing condition at enlistment, particularly a musculoskeletal condition, had increased odds of disability discharge. Risk of disability was dependent on condition category when stratified by deployment and combat status. Additional research examining conditions during pre-disability hospitalizations could provide insight on specific conditions that commonly lead to disability discharge. PMID- 26905974 TI - Selected health behaviors moderate the progression of functional limitations in persons with multiple sclerosis: Eleven years of annual follow-up. AB - BACKGROUND: Multiple sclerosis (MS), a chronic neurological disease typically diagnosed in young adulthood, presents with a wide variety of symptoms, impairments and functional limitations. Given the chronic, unpredictable and long term nature of this disease, preserving function is essential. OBJECTIVE: The purpose of this study was to identify psychosocial and behavioral factors that might influence the trajectory of functional limitation through eleven years of longitudinal follow-up of a sample of persons with MS. METHODS: Participants (N = 606) completed measures of health behaviors, related constructs and functional limitations annually over eleven years. Longitudinal measures of functional limitations were analyzed using random-effects regression that allows for study of individual differences in the trajectories of a measure. Using the best fitting quadratic growth model, we tested the within and between-person effects of Nutrition, Interpersonal Relationships, Exercise, Stress Management, Health Responsibilities, Spiritual Growth, Self-rated Health and Barriers, controlling for Age, Year since Diagnosis and Year of Dropout, on Functional Limitations in the 11th year. RESULTS: After adjusting for covariates, higher mean scores for Exercise and Self-rated Health were related to lower levels of Functional Limitations in Year 11. Higher mean scores for Stress Management, Health Responsibilities and Barriers were related to higher levels of Functional Limitations in Year 11. Higher mean Exercise scores and lower mean Health Responsibilities scores were related to slower rates of progression of functional limitations in Year 11. CONCLUSION: Findings suggest that the highly variable trajectory of functional limitations in MS may be extended and shaped through health behavior strategies. PMID- 26905975 TI - Trips to medical care among persons with disabilities: Evidence from the 2009 National Household Travel Survey. AB - BACKGROUND: Persons with disabilities experience multiple barriers to obtaining necessary medical care. Problems with access to transportation and provider choice could lead to longer travel distances and longer travel times to medical appointments. OBJECTIVE/HYPOTHESIS: 1) Persons with disabilities travel further distances to receive necessary care, holding other variables constant. 2) Travel to medical appointments takes a longer amount of time for persons with disabilities, controlling for distance, mode of transportation and other factors. 3) Disability is the key factor influencing access to transportation options, holding other variables constant. METHODS: The 2009 National Household Travel Survey (NHTS) is used to examine travel patterns of persons with disabilities as they access medical care. Logistic regressions are run on distance to medical appointments, time taken for travel to medical appointments, and access to private vehicle. RESULTS: There is no difference in the distance traveled, but trips to medical care by persons with disabilities take longer amounts of time than trips taken by persons without disabilities, holding other variables constant. Access to private transportation is similar for both persons with and without disabilities. CONCLUSIONS: Persons with disabilities experience longer travel times to receive medical care, despite traveling similar distances and having similar access to private vehicles. PMID- 26905977 TI - Smoking Prevalence and Cessation Before and During Pregnancy: Data From the Birth Certificate, 2014. AB - OBJECTIVES: This report presents findings for 2014 on maternal smoking prevalence and cessation before and during pregnancy as collected on the 2003 U.S. Standard Certificate of Live Birth, for a 46-state and District of Columbia reporting area, representing 95% of all births in the United States. METHODS: Cigarette smoking and cessation rates 3 months before and during pregnancy are presented by maternal age; race and ethnicity; marital status; educational attainment; source of payment at delivery (private insurance, Medicaid, and self-pay); receipt of benefits from the Special Supplemental Nutrition Program for Women, Infants, and Children; prenatal care initiation; and jurisdiction. RESULTS: About 1 in 10 women who gave birth in 2014 smoked during the 3 months before pregnancy (10.9%), and about one-quarter of these women (24.2%) did not smoke during pregnancy (i.e., quit before pregnancy). The smoking rate at any time during pregnancy was 8.4%, with 20.6% of women who smoked in the first or second trimesters quitting by the third trimester. Smoking during pregnancy was more prevalent for women aged 20-24 (13.0%) than for other ages, and by race and Hispanic origin, the highest rate was for non- Hispanic American Indian or Alaska Native women (18.0%). Smoking during pregnancy ranged from 1.8% in California to 27.1% in West Virginia. The highest smoking cessation rates before and during pregnancy were for women with the highest educational attainment, private insurance, and non Hispanic Asian and Hispanic race and ethnicity. On average, women who continued to smoke during pregnancy smoked fewer cigarettes as the pregnancy progressed, from 13 per day before pregnancy to 9 per day by the third trimester. PMID- 26905978 TI - Possible linkage between neuronal recruitment and flight distance in migratory birds. AB - New neuronal recruitment in an adult animal's brain is presumed to contribute to brain plasticity and increase the animal's ability to contend with new and changing environments. During long-distance migration, birds migrating greater distances are exposed to more diverse spatial information. Thus, we hypothesized that greater migration distance in birds would correlate with the recruitment of new neurons into the brain regions involved with migratory navigation. We tested this hypothesis on two Palearctic migrants - reed warblers (Acrocephalus scirpaceus) and turtle doves (Streptopelia turtur), caught in Israel while returning from Africa in spring and summer. Birds were injected with a neuronal birth marker and later inspected for new neurons in brain regions known to play a role in navigation - the hippocampus and nidopallium caudolateral. We calculated the migration distance of each individual by matching feather isotopic values (delta(2)H and delta(13)C) to winter base-maps of these isotopes in Africa. Our findings suggest a positive correlation between migration distance and new neuronal recruitment in two brain regions - the hippocampus in reed warblers and nidopallium caudolateral in turtle doves. This multidisciplinary approach provides new insights into the ability of the avian brain to adapt to different migration challenges. PMID- 26905976 TI - The role of kinetic context in apparent biased agonism at GPCRs. AB - Biased agonism describes the ability of ligands to stabilize different conformations of a GPCR linked to distinct functional outcomes and offers the prospect of designing pathway-specific drugs that avoid on-target side effects. This mechanism is usually inferred from pharmacological data with the assumption that the confounding influences of observational (that is, assay dependent) and system (that is, cell background dependent) bias are excluded by experimental design and analysis. Here we reveal that 'kinetic context', as determined by ligand-binding kinetics and the temporal pattern of receptor-signalling processes, can have a profound influence on the apparent bias of a series of agonists for the dopamine D2 receptor and can even lead to reversals in the direction of bias. We propose that kinetic context must be acknowledged in the design and interpretation of studies of biased agonism. PMID- 26905979 TI - Microplastics Alter the Properties and Sinking Rates of Zooplankton Faecal Pellets. AB - Plastic debris is a widespread contaminant, prevalent in aquatic ecosystems across the globe. Zooplankton readily ingest microscopic plastic (microplastic, < 1 mm), which are later egested within their faecal pellets. These pellets are a source of food for marine organisms, and contribute to the oceanic vertical flux of particulate organic matter as part of the biological pump. The effects of microplastics on faecal pellet properties are currently unknown. Here we test the hypotheses that (1) faecal pellets are a vector for transport of microplastics, (2) polystyrene microplastics can alter the properties and sinking rates of zooplankton egests and, (3) faecal pellets can facilitate the transfer of plastics to coprophagous biota. Following exposure to 20.6 MUm polystyrene microplastics (1000 microplastics mL(-1)) and natural prey (~1650 algae mL(-1)) the copepod Calanus helgolandicus egested faecal pellets with significantly (P < 0.001) reduced densities, a 2.25-fold reduction in sinking rates, and a higher propensity for fragmentation. We further show that microplastics, encapsulated within egests of the copepod Centropages typicus, could be transferred to C. helgolandicus via coprophagy. Our results support the proposal that sinking faecal matter represents a mechanism by which floating plastics can be vertically transported away from surface waters. PMID- 26905980 TI - Spin-Casting Polymer Brush Films for Stimuli-Responsive and Anti-Fouling Surfaces. AB - Surfaces modified with amphiphilic polymers can dynamically alter their physicochemical properties in response to changes of their environmental conditions; meanwhile, amphiphilic polymer coatings with molecular hydrophilic and hydrophobic patches, which can mitigate biofouling effectively, are being actively explored as advanced coatings for antifouling materials. Herein, a series of well-defined amphiphilic asymmetric polymer brushes containing hetero side chains, hydrophobic polystyrene (PS) and hydrophilic poly(ethylene glycol) (PEG), was employed to prepare uniform thin films by spin-casting. The properties of these films were investigated by water contact angle, X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), and quartz crystal microbalance (QCM). AFM showed smooth surfaces for all films with the roughness less than 2 nm. The changes in water contact angle and C/O ratio (XPS) evidenced the enrichment of PEG or PS chains at film surface after exposed to selective solvents, indicative of stimuli- responsiveness. The adsorption of proteins on PEG functionalized surface was quantified by QCM and the results verified that amphiphilic polymer brush films bearing PEG chains could lower or eliminate protein-material interactions and resist to protein adsorption. Cell adhesion experiments were performed by using HaCaT cells and it was found that polymer brush films possess good antifouling ability. PMID- 26905981 TI - Prevention of neonatal early onset GBS sepsis: A clear protocol is better than none--or several. AB - Revised New Zealand consensus guidelines on the prevention of early-onset group B streptococcus sepsis in the newborn are presented in this issue of the Journal. We provide some context for these recommendations and discuss issues considered by the multidisciplinary group in formulating the guidelines. PMID- 26905982 TI - Mandatory regulation or self-regulation in the age of the Volkswagen saga. PMID- 26905983 TI - Fast, fair climate action crucial for health and equity. PMID- 26905984 TI - Pacific Islands Families Study: Signs of puberty are associated with physical growth at ages 9 and 11 years. AB - AIM: To prospectively observe, at ages 9 and 11, the relationship of parental report of pubertal signs with height, weight, body mass index and birth weight in children of the Pacific Islands Families cohort born in the year 2000. METHOD: At ages 9 and 11 years a parental questionnaire assessed five gender-specific pubertal signs for 619 children and height and weight were objectively measured. At 9 years, body fatness was derived from frequency bioimpedance analysis. Birth weight was obtained from hospital records. Anthropometric measures of children with and without pubertal signs at each age were compared. RESULTS: At both 9 and 11 years, more than 80% of both boys' and girls' parents reported the presence of a growth spurt. The growth trajectory between 9 and 11 years was steep compared to the Centers for Disease Control reference child. At age 11, girls showing pubertal signs had substantially greater height, weight and body mass indexes than girls who did not. Girls with a growth spurt at age 9 years (91%) had a heavier birth weight than those without; a difference of 250 g (95% CI 50, 450 g). CONCLUSION: The relationships between birth weight, rapid growth in childhood and early pubertal signs are complex. In addition to biological factors, food security and socioeconomic factors need to be addressed to ensure that the children of these children are exposed to an environment that is supportive of healthy rates of growth and development. PMID- 26905985 TI - Intravenous magnesium sulphate as an adjuvant therapy in acute exacerbations of chronic obstructive pulmonary disease: a single centre, randomised, double blinded, parallel group, placebo-controlled trial: a pilot study. AB - AIM: To investigate the effects on lung function of IV magnesium in acute exacerbations of COPD (AECOPD), when given in conjunction with standard bronchodilator therapy. METHODS: This was a pilot study to a randomised, double blinded, placebo-controlled trial. 30 patients presenting to ED with AECOPD were included. In addition to standard bronchodilator therapy, 17 patients were given saline, and 13 received 2 g of magnesium sulphate intravenously. Spirometry was carried out at presentation (TA), after initial standard bronchodilator therapy (TB) and immediately (T0), at 60 minutes (T60) and 120 minutes (T120) after trial drug infusion. Primary outcomes were percentage change in FEV1 and FVC at T0, T60 and T120. Secondary outcomes were admission rates, length of stay and requirement for NIV or mechanical ventilation. Trial registration (ANZCTR), ACTRN12613000837729. RESULTS: Greater improvements were seen in FEV1 at T0, T60 and T120 compared to TB in magnesium group (at T120, mean percentage change in FEV1 was 27.07% with magnesium versus 11.39% in the placebo group, 95%CI 3.7 to 27.7, p=0.01). Similar significantly greater improvements were noted with FVC in the magnesium group, compared to TB. CONCLUSIONS: IV magnesium sulphate used as an adjunct therapy to standard bronchodilators in AECOPD presenting to ED may improve lung function in the short term. PMID- 26905986 TI - Infertility and outcomes for infertile women in Otago and Southland. AB - AIM: To establish the burden of infertility in women residing in Otago and Southland. METHODS: A survey of women aged 25-50 years residing in Otago and Southland was conducted to determine the proportions that experienced infertility, sought medical help and resolved their infertility, and to assess the determinants of these outcomes. RESULTS: Of the 1,125 participants, 21.7% (95% CI 19.1-24.4%) had experienced infertility, defined as ever having tried unsuccessfully to conceive for at least 12 months, increasing to 25.3% (22.6 28.1%) when seeking medical help was included in this measure. Seeking medical help to conceive among those having difficulties was very common and most women resolved their first episode of infertility with a live birth. Infertility was more common with extremes of body mass index, higher education and not being in a heterosexual relationship. Infertility resolution was less likely for those over 35 years at onset of infertility and with increasing social deprivation. DISCUSSION: Infertility was common in women residing in Otago and Southland. Despite high levels of infertility resolution overall, those with higher deprivation appeared disadvantaged. Further research is needed to provide national estimates and investigate factors influencing infertility outcomes. PMID- 26905987 TI - The experiences, motivations, and opinions of New Zealand's live liver donors. AB - AIM: To explore the motivations and experiences of New Zealand's live liver donors, and their opinions on New Zealand's current organ donation system. METHOD: An anonymous questionnaire was sent to all 45 of New Zealand's live liver donors in November 2012. RESULT: 21 responses were collated with an even gender split. Half of the participants were parents of the recipient. Despite the risks of surgery and associated post-surgical pain, all participants were satisfied by how the transplant went for the recipient and for themselves. 90% thought people should save lives if they can, with 18 (86%) disagreeing with New Zealand's current method of allowing family members to veto the deceased person's wishes on organ donation (on their driver's license). 95% thought that education was important in encouraging people to donate. CONCLUSION: This unique and informed group have experienced both what it means to have a loved one waiting for a transplant and how it feels to be an organ donor. If New Zealand is serious about wanting to increase deceased organ donation rates, we should consider the experiences such as those who have undergone live donation. PMID- 26905988 TI - Attitudes and risk of withdrawal in general surgical registrars. AB - AIMS: To determine the risk of withdrawal from training of Australian and New Zealand general surgical registrars, and to investigate factors associated with increased risk. METHODS: An invitation to participate in an online survey was distributed to all Australian and New Zealand general surgical registrars by the Royal Australasian College of Surgeons. RESULTS: 142 of 550 (26%) participants completed the survey. Overall, 54% (n=77) of respondents had considered leaving surgical training. Female trainees were significantly more likely to consider leaving training compared to males (65% vs 47%, p=0.036, OR 2.1). Respondents who studied in Australia or New Zealand, compared to overseas, were also significantly more likely to consider leaving surgical training (59% vs 35%, p=0.023, OR 2.7). The most common reason for potential withdrawal was poor lifestyle and quality of life during surgical training. Trainees at risk of withdrawal felt less supported, less satisfied with teaching and less confident in their operative skills. CONCLUSION: Female and locally-trained general surgical registrars are at a higher risk of withdrawal during their training programme for a number of reasons. At risk trainees are also less satisfied with their programme. PMID- 26905989 TI - The prevention of early-onset neonatal group B streptococcus infection: New Zealand Consensus Guidelines 2014. AB - AIMS: Group B streptococcal (GBS) disease is the leading cause of early-onset neonatal sepsis in New Zealand. Disease follows vertical transmission of GBS from the mother, which can largely be prevented by intravenous intrapartum antibiotics. A 2004 New Zealand guideline recommended using clinical risk factors to identify mothers who would qualify for intrapartum antibiotics. An expert multidisciplinary group met to reconsider these guidelines in the light of a two year survey of the incidence of early onset GBS neonatal sepsis. METHODS: Representatives from the New Zealand College of Midwives, the Fetus and Newborn Committee of the Paediatric Society of New Zealand, the Royal New Zealand College of General Practitioners, the New Zealand Committee of the Royal Australian and New Zealand College of Obstetricians and Gynaecologists, the New Zealand sub Committee of the Australasian Society of Infectious Diseases, and the Canterbury Home Birth Association met to review the literature and the most recent New Zealand data. RESULTS: The multidisciplinary group noted that the estimated incidence of early-onset GBS sepsis had halved over a 10-year period to be 0.26 per 1,000 live births in 2009-11 and that there were missed opportunities for preventing GBS infection. Consensus was reached that adoption of a national guideline on prevention and management of early onset GBS neonatal sepsis by all practitioners and District Health Boards would have the greatest potential to further reduce the incidence. CONCLUSION: A risk-based GBS prevention strategy continues to be recommended as being the most clinically and cost effective for the New Zealand context. Universal routine antenatal GBS screening is not recommended. PMID- 26905990 TI - Renal replacement therapy associated with lithium nephrotoxicity in New Zealand. AB - AIM: To document the numbers and characteristics of New Zealand patients commencing renal replacement therapy because of end-stage kidney disease attributed to lithium treatment, and to calculate incidence rates. METHOD: Data on such patients were provided by the Australia and New Zealand Dialysis and Transplant Registry from the start of the Registry in 1977 until 2013. Numbers of patients prescribed lithium in the community were provided by the Ministry of Health for 2009-2013; earlier years had fewer than 96% of prescriptions for lithium linked to individuals by their unique National Health Index number. Time trends were analysed by linear, logistic and Poisson regression. Incidence rates were also calculated for five-year periods. RESULTS: Thirty-five new patients were located with 'lithium toxicity' as their primary renal disease, starting the year after 'lithium toxicity' was included in the standard list (1995). A broader search for lithium within 'other' causes and 'other' comorbidities did not yield further patients. The mean age at the start of renal replacement therapy was 61.1 years (SD 9.2). Twenty-five patients were female. For 1996 onwards, new patient numbers increased on average by 8% per year (95% CI 1 to 15%) and incidence rates increased by 7% per year (95% CI 0 to 14%), an approximate doubling per decade. Form 2007-2011, the average annual incidence per million population was 0.74 (95% CI 0.43 to 1.21) for New Zealand, similar to that reported elsewhere: 0.78 (95% CI 0.67 to 0.90) for Australia and 0.91 (95% CI 0.50 to 1.52) for southern Sweden. Prescription rates across the three countries were also similar. In New Zealand between 2009 and 2013, over 7,500 patients were prescribed lithium each year. CONCLUSION: Dosing and monitoring of patients prescribed lithium should follow guidelines, not only to avoid future psychiatric episodes and acute toxicity but also because such adherence may reduce uncommon but serious outcomes of long-term treatment such as end-stage kidney disease. PMID- 26905991 TI - Is the statement that if a person is off work for 70 days the chance of ever getting back to work is 35% justified? AB - The Australasian Faculty of Occupational and Environmental Medicine released a position statement which included statements about the chance of ever getting back to work if a person is off work for 20, 45 and 70 days. These statements are being repeated by government and non-government agencies in New Zealand and Australia. They have been presented with the intent to influence public policy. They are presented to general practitioners in the context of certifying people as unfit for work. The statements are based on an incorrect interpretation of the referenced study, are not justified and should be corrected. PMID- 26905992 TI - Potential new regulatory options for e-cigarettes in New Zealand. AB - While e-cigarette usage has grown rapidly in New Zealand and around the world, the scientific evidence base regarding the net benefits and risks of these types of products at the population level remains uncertain. The health-based policy experience is also minimal. Here, we analyse plausible future regulatory options for e-cigarettes that the New Zealand Government could explore, and that further research could help clarify. These options include: (1) a full free market (an option we doubt is desirable for multiple reasons); (2) controlled increased access through: (a) pharmacy only, (b) pharmacy only plus sales by prescription/ to licensed vapers; (c) additional controls through non-profit supply/distribution (eg, public hospital pharmacies); (3) increased restrictions compared with current (eg, adopting a complete ban on self-imports and use). In addition, we consider mechanisms to improve product quality and safety, and argue that policy makers should take great care when regulating e-cigarettes, given the scientific uncertainty and the role of commercial vested interests. PMID- 26905993 TI - A case of botulism in New Zealand. AB - We describe the first case of food-borne botulism seen in New Zealand for 30 years. Botulism is an important diagnosis to consider in a patient with rapidly progressive descending paralysis and normal sensorium. Early recognition, timely institution of intensive care support and administration of botulism antitoxin are the most important aspects of management. PMID- 26905994 TI - Bullous Mantoux Reaction. PMID- 26905995 TI - Equitable care for those with rheumatic heart disease. PMID- 26905996 TI - Ticagrelor in the Real World: The Midland Regional Cardiac Network Experience. PMID- 26905997 TI - Children's positive attitudes towards the tobacco industry is associated with initiation of smoking. PMID- 26905998 TI - Trends and patterns in medical student research and publishing in New Zealand. PMID- 26906000 TI - Evaluation of the efficacy of a portable LIBS system for detection of CWA on surfaces. AB - Laser-induced breakdown spectroscopy (LIBS) is a laser-based optical technique particularly suited for in situ surface analysis. A portable LIBS instrument was tested to detect surface chemical contamination by chemical warfare agents (CWAs). Test of detection of surface contamination was carried out in a toxlab facility with four CWAs, sarin (GB), lewisite (L1), mustard gas (HD), and VX, which were deposited on different substrates, wood, concrete, military green paint, gloves, and ceramic. The CWAs were detected by means of the detection of atomic markers (As, P, F, Cl, and S). The LIBS instrument can give a direct response in terms of detection thanks to an integrated interface for non-expert users or so called end-users. We have evaluated the capability of automatic detection of the selected CWAs. The sensitivity of our portable LIBS instrument was confirmed for the detection of a CWA at surface concentrations above 15 MUg/cm(2). The simultaneous detection of two markers may lead to a decrease of the number of false positive. PMID- 26905999 TI - Significant effect of age on docetaxel pharmacokinetics in Japanese female breast cancer patients by using the population modeling approach. AB - PURPOSE: Docetaxel is frequently used in the treatment of a wide variety of solid tumors, including breast cancer. The aim of this study is to obtain the population pharmacokinetic parameters of docetaxel in Japanese female patients with breast cancer. METHODS: Blood samples from 24 patients were collected sequentially before and after docetaxel infusion. Genomic DNA was isolated from the peripheral blood and genotyped for the selected polymorphisms in the candidate genes of drug transporters and metabolizing enzymes. The influence of patient characteristics on the pharmacokinetics of docetaxel was evaluated using the nonlinear-mixed-effect modeling program, NONMEM. As a basis for comparison, the pharmacokinetics of another taxane paclitaxel in 41 separate female patients with breast cancer was calculated. RESULTS: A two-compartment model adequately described the pharmacokinetic profiles of docetaxel. The population mean estimates of the total body clearance for patients aged 58 years or less and the central volume of distribution for docetaxel were 32.6 L/h and 5.77 L, respectively. In patients over 58 years, the clearance was 24 % higher than that in the younger patients. No influences of the genotypes examined were noted on the clearance of docetaxel. The clearance of paclitaxel was not affected by patient age. CONCLUSIONS: Patients over the age of 58 years showed significantly higher clearance of docetaxel than that in patients aged 58 years or less. Since the clearance of paclitaxel was not affected by the age, it is possible that the pharmacokinetic mechanisms of docetaxel might be specifically affected by age in females. PMID- 26906001 TI - Effect of activated carbon and biochars on the bioavailability of polycyclic aromatic hydrocarbons in different industrially contaminated soils. AB - Coal production negatively affects the environment by the emission of polycyclic aromatic hydrocarbons (PAHs). Two soils (KOK and KB) from a coking plant area was investigated and their total PAH concentration was 40 and 17 mg/kg for the sum (?) 16 US EPA PAHs, respectively. A third soil was sampled from a bitumen plant area and was characterized by 9 mg/kg ?16 US EPA PAHs. To reduce the freely dissolved concentration (Cfree) of the PAHs in the soil pore water, active carbon (AC) and two biochars pyrolysed from wheat straw (biochar-S) and willow (biochar W) were added to the soils at 0.5-5 % (w/w), each. The AC performed best and reduced the Cfree by 51-98 % already at the lowest dose. The biochars needed doses up to 2.5 % to significantly reduce the Cfree by 44-86 % in the biochar-S and by 37-68 % in the biochar-W amended soils. The high black carbon (BC) content of up to 2.3 % in the Silesian soils competed with the sorption sites of the carbon amendments and the performance of the remediation was a consequence of the contaminant's source and the distribution between the BC and the AC/biochars. In contrast, the carbon amendment could best reduce the Cfree in the Lublin soil where the BC content was normal (0.05 %). It is therefore crucial to know the contaminant's source and history of a sample/site to choose the appropriate carbon amendment not only for remediation success but also for economic reasons. PMID- 26906002 TI - Decontaminating soil organic pollutants with manufactured nanoparticles. AB - Organic pollutants in soils might threaten the environmental and human health. Manufactured nanoparticles are capable to reduce this risk efficiently due to their relatively large capacity of sorption and degradation of organic pollutants. Stability, mobility, and reactivity of nanoparticles are prerequisites for their efficacy in soil remediation. On the basis of a brief introduction of these issues, this review provides a comprehensive summary of the application and effectiveness of various types of manufactured nanoparticles for removing organic pollutants from soil. The main categories of nanoparticles include iron (oxides), titanium dioxide, carbonaceous, palladium, and amphiphilic polymeric nanoparticles. Their advantages (e.g., unique properties and high sorption capacity) and disadvantages (e.g., high cost and low recovery) for soil remediation are discussed with respect to the characteristics of organic pollutants. The factors that influence the decontamination effects, such as properties, surfactants, solution chemistry, and soil organic matter, are addressed. PMID- 26906003 TI - Sewage sludge hazardous assessment: chemical evaluation and cytological effects in CHO-k1 cells. AB - Application of sewage sludge in agricultural lands is a growing practice in several countries due to its numerous benefits to soil and crops, where chemical and pathogen levels are determined by corresponding legislation. However, the presence of contaminants in residues must always be controlled before application due to their dangerous effects over the ecosystem and potential risks to human health. The main objective of this study was to integrate biological and chemical analysis in order to help elucidating the residue potential toxic, cytotoxic, and mutagenic effects. We evaluate samples of sewage sludge before and after the sanitizing treatment with lime in cytokinesis-block assay using CHO-k1 culture cells. The sanitizing treatment promoted a decrease in pathogen levels, which is the main purpose of this process. Even with chemical levels below the established by environmental agencies, results showed sewage sludge ability to enhance genotoxic and mutagenic effects, proving that residue should be handled with caution in order to minimize its environmental and human risk. PMID- 26906004 TI - On the geotechnical characterisation of the polluted submarine sediments from Taranto. AB - This paper reports the results of the first geomechanical laboratory experiments carried out on the polluted submarine clayey sediments of the Mar Piccolo in Taranto (South of Italy). The study had to face with extreme difficulties for the very soft consistency of the sediments and the contaminants. The mineralogy, composition and physical properties of the sediments were analysed, along with their compression and shearing behaviour. The investigation involved sediments up to about 20 m below the seafloor, along three vertical profiles in the most polluted area of the Mar Piccolo, facing the Italian Navy Arsenal. The experimental results were used to derive a preliminary geotechnical model of the site, necessary for the selection and design of the most sustainable in situ mitigation solutions. Moreover, the experimental data reveal that the clayey sediments of the most polluted top layer do not follow the classical geotechnical correlations for normally consolidated deposits. This seems to open interesting perspectives about the effects of pollutants on the geotechnical behaviour of the investigated sediments. PMID- 26906005 TI - Fractional distribution and risk assessment of heavy metals in sediments collected from the Yellow River, China. AB - Bohai Sea is one of the most intensively exploited region in the world and its environment has been severely impacted by the extensive human activities. The Yellow River is the most important river which connects with the Bohai Sea. Therefore, this study focused on analyzing heavy metals (HMs) in 21 surface sediment samples collected from the Yellow River, China. Sequential extraction procedure (SEP), proposed by the Community Bureau of Reference (BCR), was applied in the present study to determine the concentration and fractionation characteristics of these HMs. The aim of this study was to investigate the spatial distribution, fractionation, risk assessment, and sources of HMs, including copper (Cu), zinc (Zn), lead (Pb), chromium (Cr), iron (Fe), manganese (Mn), and nickel (Ni). The results obtained from this research will play a significant role in understanding the migration, transformation, and accumulation of HMs for future research in study area. Results of fractionation revealed that most of the HMs in the study area mainly existed in residual fraction; however, Mn mostly existed in exchangeable fraction. A high percentage of reducible fractions was found for Cu and Pb. The mean contamination factor (Cf) values indicated that Pb was the highest. It was >1 and showed moderate contamination, followed by Cr, Cu, Mn, Ni, and Zn, had <1 and indicated low contamination. Among studied HMs Pb had higher enrichment factor (EF) as compared to others. Significant positive correlations within all studied HMs and principal component analysis (PCA) results indicated their common sources, however, Pb showed the different contamination sources. The total contents of HMs in sediment were compared with the threshold effect level (TEL) and probable effect level (PEL) sediment quality guideline (TEL/PEL-based SQGs) values for trace metals in sediment, as well as literature reported data for comparative purposes, which indicated that the selected river in present study is not severe. PMID- 26906006 TI - 14th congress of combustion by-products and their health effects-origin, fate, and health effects of combustion-related air pollutants in the coming era of bio based energy sources. AB - The 14th International Congress on Combustion By-Products and Their Health Effects was held in Umea, Sweden from June 14th to 17th, 2015. The Congress, mainly sponsored by the National Institute of Environmental Health Sciences Superfund Research Program and the Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning, focused on the "Origin, fate and health effects of combustion-related air pollutants in the coming era of bio based energy sources". The international delegates included academic and government researchers, engineers, scientists, policymakers and representatives of industrial partners. The Congress provided a unique forum for the discussion of scientific advances in this research area since it addressed in combination the health-related issues and the environmental implications of combustion by products. The scientific outcomes of the Congress included the consensus opinions that: (a) there is a correlation between human exposure to particulate matter and increased cardiac and respiratory morbidity and mortality; (b) because currently available data does not support the assessment of differences in health outcomes between biomass smoke and other particulates in outdoor air, the potential human health and environmental impacts of emerging air-pollution sources must be addressed. Assessment will require the development of new approaches to characterize combustion emissions through advanced sampling and analytical methods. The Congress also concluded the need for better and more sustainable e waste management and improved policies, usage and disposal methods for materials containing flame retardants. PMID- 26906007 TI - Simultaneous determination of multiclass emerging contaminants in aquatic plants by ultrasound-assisted matrix solid-phase dispersion and GC-MS. AB - A multiresidue method was developed for the simultaneous determination of 31 emerging contaminants (pharmaceutical compounds, hormones, personal care products, biocides, and flame retardants) in aquatic plants. Analytes were extracted by ultrasound-assisted matrix solid-phase dispersion (UA-MSPD) and determined by gas chromatography-mass spectrometry after sylilation, The method was validated for different aquatic plants (Typha angustifolia, Arundo donax, and Lemna minor) and a semiaquatic cultivated plant (Oryza sativa) with good recoveries at concentrations of 100 and 25 ng g-1 wet weight, ranging from 70 to 120 %, and low method detection limits (0.3 to 2.2 ng g-1 wet weight). A significant difference of the chromatographic response was observed for some compounds in neat solvent versus matrix extracts, and therefore, quantification was carried out using matrix-matched standards in order to overcome this matrix effect. Aquatic plants taken from rivers located at three Spanish regions were analyzed, and the compounds detected were parabens, bisphenol A, benzophenone-3, cyfluthrin, and cypermethrin. The levels found ranged from 6 to 25 ng g-1 wet weight except for cypermethrin that was detected at 235 ng g-1 wet weight in O. sativa samples. PMID- 26906008 TI - Mass size distribution and source identification of particulate matter metal components at four urban sites and a background site of Istanbul. AB - In this study, the size distribution characteristics and metal contents of particulate matter (PM) have been determined. In this scope, PM sampling has been done at five stations in Istanbul. PM filter samples were collected for eight different sizes using the Anderson cascade impactor. PM filters were decomposed and analyzed for 20 metals. The highest median concentration for Fe, Ca, K, and Mg, known as soil metals, were observed as follows: Fe and Ca were observed at Goztepe station (1.20 and 8.28 MUg/m(3)), K was observed at Kilyos station (0.33 MUg/m(3)), and Mg was observed at Avcilar station (0.37 MUg/m(3)). The highest median concentrations for Zn, Cu, Pb, Ni, Cr, V, As, Se, Co, and Cd, known as anthropogenic metals, were observed at Avcilar, Goztepe, and Besiktas stations. Although the lowest metal concentrations was determined at Kilyos stations that was selected as the urban background. The enrichment factors (EFs) of most metals in the fine PM is higher than those in the coarse mode. According to the factor analyses, the most important emission source was observed to be industrial facilities at Avcilar; traffic at Besiktas; traffic and domestic heating at Goztepe; and domestic heating, sea salt aerosols, and ship traffic (in the Bosphorus Channel of Istanbul) at Rasathane. PMID- 26906009 TI - Pharmacogenetic characterization of naturally occurring germline NT5C1A variants to chemotherapeutic nucleoside analogs. AB - BACKGROUND: Mutations or alterations in expression of the 5' nucleotidase gene family can lead to altered responses to treatment with nucleoside analogs. While investigating leukemia susceptibility genes, we discovered a very rare p.L254P NT5C1A missense variant in the substrate recognition motif. Given the paucity of cellular drug response data from the NT5C1A germline variation, we characterized p.L254P and eight rare variants of NT5C1A from genomic databases. MATERIALS AND METHODS: Through lentiviral infection, we created HEK293 cell lines that stably overexpress wild-type NT5C1A, p.L254P, or eight NT5C1A variants reported in the National Heart Lung and Blood Institute Exome Variant Server (one truncating and seven missense). IC50 values were determined by cytotoxicity assays after exposure to chemotherapeutic nucleoside analogs (cladribine, gemcitabine, 5 fluorouracil). In addition, we used structure-based homology modeling to generate a three-dimensional model for the C-terminal region of NT5C1A. RESULTS: The p.R180X (truncating), p.A214T, and p.L254P missense changes were the only variants that significantly impaired protein function across all nucleotide analogs tested (>5-fold difference vs. wild-type; P<0.05). Several of the remaining variants individually showed differential effects (both more and less resistant) across the analogs tested. The homology model provided a structural framework to understand the impact of NT5C1A mutants on catalysis and drug processing. The model predicted active site residues within NT5C1A motif III and we experimentally confirmed that p.K314 (not p.K320) is required for NT5C1A activity. CONCLUSION: We characterized germline variation and predicted protein structures of NT5C1A. Individual missense changes showed considerable variation in response to the different nucleoside analogs tested, which may impact patients' responses to treatment. PMID- 26906010 TI - Australian paediatric perspective on DNACPR. PMID- 26906011 TI - CORR Insights((r)): Reoperation After Cervical Disc Arthroplasty Versus Anterior Cervical Discectomy and Fusion: A Meta-analysis. PMID- 26906012 TI - Acute encephalitis with refractory, repetitive partial seizures: Pathological findings and a new therapeutic approach using tacrolimus. AB - Acute encephalitis with refractory, repetitive partial seizures (AERRPS) is characterized by prolonged severe seizures and a high-grade fever. We experienced a boy with severe AERRPS with frequent partial seizures that exhibited right-side predominance. The patient required the continuous intravenous administration of many antiepileptic drugs and respirator management for several months. Methylprednisolone pulse therapy and intravenous immunoglobulin administration were only temporarily effective. The MRI and EEG showed the abnormality in the left occipital lobe. Although occipital lobectomy was performed, his seizures continued. His cerebrospinal fluid exhibited elevated protein and proinflammatory cytokine levels, and was positive for anti-glutamate receptor epsilon2 antibodies. Pathological examination showed infiltration of many neutrophilic leukocytes, T cells, and microglia in the area exhibiting severe spongiosis. We thought that the exaggerated microglia and T-cell responses were related to the pathogenesis of the patient's seizures, and we therefore initiated treatment with tacrolimus. As a result, many of the daily seizure clusters were ameliorated, and the patient was discharged. We attempted to discontinue the tacrolimus twice, but the patient's seizure clusters recurred each time. This is the first case report of the pathological findings of AERRPS and showing an effective therapeutic approach using tacrolimus. Tacrolimus may be an effective immunosuppressant, especially for patients with severe AERRPS. PMID- 26906013 TI - Aggravation of atonic seizures by rufinamide: A case report. AB - BACKGROUND: Rufinamide is a novel antiepileptic drug used as adjunctive therapy in patients with Lennox-Gastaut syndrome and provides seizure control especially in tonic and atonic seizures. Rufinamide is expected to be effective in intractable epilepsy when atonic and tonic seizures exist. However, rufinamide induced seizure aggravation has been reported in a few patients, which was not associated with a specific type of seizure. CASE: A 12-year-old boy with intractable epilepsy had tonic and atonic seizures despite treatment with valproic acid (3000mg/day), levetiracetam (3000mg/day) and clobazam (40mg/day). Rufinamide was administered as adjuvant therapy. After 2weeks on rufinamide, he experienced atonic seizure worsening, and the frequency of epileptic discharges increased. The deterioration in seizure frequency and epileptiform discharges resolved when rufinamide was discontinued. CONCLUSION: Rufinamide may aggravate atonic seizures in patients with intractable epilepsy. PMID- 26906014 TI - High-Dose Perioperative Atorvastatin and Acute Kidney Injury Following Cardiac Surgery: A Randomized Clinical Trial. AB - IMPORTANCE: Statins affect several mechanisms underlying acute kidney injury (AKI). OBJECTIVE: To test the hypothesis that short-term high-dose perioperative atorvastatin would reduce AKI following cardiac surgery. DESIGN, SETTING, AND PARTICIPANTS: Double-blinded, placebo-controlled, randomized clinical trial of adult cardiac surgery patients conducted from November 2009 to October 2014 at Vanderbilt University Medical Center. INTERVENTIONS: Patients naive to statin treatment (n = 199) were randomly assigned 80 mg of atorvastatin the day before surgery, 40 mg of atorvastatin the morning of surgery, and 40 mg of atorvastatin daily following surgery (n = 102) or matching placebo (n = 97). Patients already taking a statin prior to study enrollment (n = 416) continued taking the preenrollment statin until the day of surgery, were randomly assigned 80 mg of atorvastatin the morning of surgery and 40 mg of atorvastatin the morning after (n = 206) or matching placebo (n = 210), and resumed taking the previously prescribed statin on postoperative day 2. MAIN OUTCOMES AND MEASURES: Acute kidney injury defined as an increase of 0.3 mg/dL in serum creatinine concentration within 48 hours of surgery (Acute Kidney Injury Network criteria). RESULTS: The data and safety monitoring board recommended stopping the group naive to statin treatment due to increased AKI among these participants with chronic kidney disease (estimated glomerular filtration rate <60 mL/min/1.73 m2) receiving atorvastatin. The board later recommended stopping for futility after 615 participants (median age, 67 years; 188 [30.6%] were women; 202 [32.8%] had diabetes) completed the study. Among all participants (n = 615), AKI occurred in 64 of 308 (20.8%) in the atorvastatin group vs 60 of 307 (19.5%) in the placebo group (relative risk [RR], 1.06 [95% CI, 0.78 to 1.46]; P = .75). Among patients naive to statin treatment (n = 199), AKI occurred in 22 of 102 (21.6%) in the atorvastatin group vs 13 of 97 (13.4%) in the placebo group (RR, 1.61 [0.86 to 3.01]; P = .15) and serum creatinine concentration increased by a median of 0.11 mg/dL (10th-90th percentile, -0.11 to 0.56 mg/dL) in the atorvastatin group vs by a median of 0.05 mg/dL (10th-90th percentile, -0.12 to 0.33 mg/dL) in the placebo group (mean difference, 0.08 mg/dL [95% CI, 0.01 to 0.15 mg/dL]; P = .007). Among patients already taking a statin (n = 416), AKI occurred in 42 of 206 (20.4%) in the atorvastatin group vs 47 of 210 (22.4%) in the placebo group (RR, 0.91 [0.63 to 1.32]; P = .63). CONCLUSIONS AND RELEVANCE: Among patients undergoing cardiac surgery, high-dose perioperative atorvastatin treatment compared with placebo did not reduce the risk of AKI overall, among patients naive to treatment with statins, or in patients already taking a statin. These results do not support the initiation of statin therapy to prevent AKI following cardiac surgery. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00791648. PMID- 26906015 TI - Investigating the relationships between antisocial behaviors, psychopathic traits, and moral disengagement. AB - The present study investigated the relations between morally disengaged attitudes, psychopathic affective traits, and a variety of antisocial and risky behaviors in a sample of adults (N=181). A second aim of the study was to examine the unique contributions of moral disengagement and psychopathic traits in predicting problematic behavior while the other construct is statistically controlled. Results indicated that whereas psychopathic traits and moral disengagement were both uniquely predictive of non-violent antisocial behaviors, only remorselessness was uniquely predictive of violence and only morally disengaged attitudes were uniquely predictive of academic cheating. Differing relationships also emerged by gender. PMID- 26906016 TI - No Soldier Left Behind: The Veterans Court Solution. AB - This paper concerns one of the newer iterations of problem-solving courts: veterans treatment courts. We trace the history of problem solving court implementation and explore the functioning of an established veterans court. The focus of this exploratory, qualitative study is the courthouse workgroup and their interactions both within the veterans court and with more traditional criminal courts and criminal justice agencies. We summarize the literature on problem solving courts and the experience, insights and suggestions of the members of the court we examined. PMID- 26906018 TI - endo-Functionalized molecular tubes: selective encapsulation of neutral molecules in non-polar media. AB - Four endo-functionalized molecular tubes with urea/thiourea groups in the deep cavities have been synthesized, and their binding ability to neutral molecules studied. Very high binding affinity and selectivity have been achieved, which are rationalized by invoking the shape and electrostatic complementarity and dipole alignment. PMID- 26906017 TI - Potential health risk of allergenic pollen with climate change associated spreading capacity: Ragweed and olive sensitization in two German federal states. AB - BACKGROUND: Global climate changes may influence the geographical spread of allergenic plants thus causing new allergen challenges. OBJECTIVE: Allergy patients from two German federal states were compared for their status quo sensitization to ragweed, an establishing allergen, olive, a non-established allergen, and the native allergens birch, mugwort, and ash. METHODS: Between 2011 and 2013, 476 adult allergy patients per region were recruited. Patients completed a questionnaire, participated in a medical interview, and underwent skin prick testing and blood withdrawal for analysis of specific IgE to allergen components (ISAC technology). Data on regional pollen load from 2006 to 2011 were acquired from the German Pollen Information Service Foundation. RESULTS: Prick test reactivity to ragweed and ash, respectively, was lower in Bavaria than in NRW (ragweed: p=0.001, aOR=0.54; ash: p=0.001, aOR=0.59), whereas prick test reactivity to olive was higher (p=0.000, aOR=3.09). Prick test reactivity to birch and mugwort, respectively, did not significantly differ. 1% (1/127) of patients with prick test reactivity to ragweed showed sIgE to Amb a 1, and 65% (86/132) of olive-but-not-ash reactive patients showed sIgE to Ole e 1 (NRW: 67%, Bavaria: 65%; p=0.823, OR=0.91). Regional differences in sensitization pattern were neither explainable by cross-reactivity to pollen pan-allergens nor non exposure variables nor by reported plant population or pollen data. CONCLUSIONS: Spread of ragweed and particularly olive may result in prompt occurrence of allergic symptoms. Early identification of invasive allergens due to climate change does need time and spatial close meshed measurement of respective indicator allergens and sensitization pattern. PMID- 26906019 TI - Combined endoscopic gastrostomy ("Pull-Introducer Technique"): a new less traumatic technique for preterm and small for gestational age patients. AB - INTRODUCTION: The most common endoscopic gastrostomy technique is the "Pull Through" or Gauderer-Ponsky technique. This is a transoral technique in which the internal bumper of the tube goes in through the esophagus. However this has been shown to be traumatic and often impossible in newborns and small for gestational age (SGA) patients, therefore a transabdominal technique must be used in this cases. We have developed a new transabdominal technique which combines two classical methods. This technique avoids the inconvenience of passing the internal bumper through the esophagus. PATIENTS AND METHODS: We have used this combined technique in five SGA patients. The technique consists of inserting a replacement tube using a Pull kit as installation device. RESULTS: There were no complications during these five procedures and the patients were fed 2 hours later. DISCUSSION: The main advantage of this technique is the use of kits that are already found in endoscopy units and endoscopists are familiar with. The disadvantage is the use of a balloon tube that can break or deflate. PMID- 26906020 TI - Laparoscopic Nissen fundoplication mainly reduces the volume of acid reflux and potentially improves mucosal integrity up to the middle esophagus in neurologically impaired children detected by esophageal combined pH-multichannel intraluminal impedance measurements. AB - BACKGROUND: The aim of this study was to evaluate detailed changes of gastroesophageal reflux disease (GERD) in children before and after laparoscopic Nissen fundoplication (LNF) utilizing esophageal combined pH-multichannel intraluminal impedance (pH/MII) measurements. PATIENTS AND METHODS: Thirteen patients with neurological impairment, who received laparoscopic Nissen fundoplication (LNF) owing to refractory pathological GERD, were enrolled in this study. 24h pH/MII was conducted in all patients before and one year after LNF. Each parameter of the pH/MII was evaluated and compared each other. RESULTS: Both the mean pH index and bolus exposure index after LNF were significantly lower than those before LNF. The mean numbers of total and nonacid reflux episodes after LNF were significantly lower than those before LNF. The mean numbers of total, acid and nonacid proximal reflux episodes after LNF were significantly lower than those before LNF. The mean baseline impedance values from Z3 to Z6 after LNF were significantly higher than those before LNF. CONCLUSIONS: The present study provides new insights into the effects of LNF in pediatric patients, which prevents mainly acid reflux episodes from rising to the proximal esophagus, and is expected to improve the mucosal integrity up to the middle esophagus. PMID- 26906021 TI - Engagement of Men in Antenatal Care Services: Increased HIV Testing and Treatment Uptake in a Community Participatory Action Program in Mozambique. AB - Uptake of HIV testing and antiretroviral therapy (ART) services during antenatal care (ANC) in rural Mozambique is disappointing. To nurture supportive male engagement in ANC services, we partnered with traditional birth attendants and trained a new type of male-to-male community health agent, "Male Champions", who focused on counseling male partners to create new, male-friendly community norms around engagement in spousal/partner pregnancies. We assessed ANC service uptake using a pre-post intervention design. The intervention was associated with increases in: (1) uptake of provider-initiated counseling and testing among pregnant woman (81 vs. 92 %; p < 0.001); (2) male engagement in ANC (5 vs. 34 %; p < 0.001); and (3) uptake of ART (8 vs. 19 %; p < 0.001). When men accepted HIV testing, rates of testing rose markedly among pregnant women. With the challenges in scale-up of Option B+ in sub-Saharan Africa, similar interventions may increase testing and treatment acceptability during pregnancy. PMID- 26906022 TI - Residential Eviction and Risk of Detectable Plasma HIV-1 RNA Viral Load Among HIV Positive People Who Use Drugs. AB - We examined the relationship between residential eviction and exhibiting detectable plasma HIV-1 RNA viral load (VL) among a prospective cohort of antiretroviral therapy (ART)-exposed HIV-seropositive people who use illicit drugs (PWUD) in Vancouver, Canada. We used multivariable generalized estimating equations to estimate the effect of residential eviction on detectable VL and examine ART adherence as a mediating variable. Between June 2007 and May 2014, 705 ART-exposed participants were included in the study, among whom 500 (70.9 %) experienced at least one period of detectable VL. In a time-updated multivariable model, eviction independently increased the odds of detectable VL among those who were homeless [adjusted odds ratio (AOR) = 2.25; 95 % confidence interval (CI) 1.18-4.29] as well as not homeless (AOR = 1.76; 95 % CI 1.17-2.63) post eviction. The results of mediation analyses suggest that this association was mediated by incomplete ART adherence. These findings suggest the need for further development and evaluation of interventions to prevent evictions and promote ART adherence among PWUD facing eviction. PMID- 26906023 TI - Reporting of Adherence in the VOICE Trial: Did Disclosure of Product Nonuse Increase at the Termination Visit? AB - VOICE-a phase 2B, placebo-controlled, randomized trial testing daily use of an antiretroviral tablet (tenofovir or Truvada) or daily use of tenofovir gel in 5029 women from South Africa, Uganda, and Zimbabwe-found none of the drug regimens effective in reducing HIV-1 acquisition in the intent-to-treat analysis. More than half of women assigned to active products in a case cohort sample had no drug detected in any plasma specimens tested during the trial. Yet, in response to questions asked of participants during the trial, >=90 % of doses were reportedly taken. To explore factors associated with low adherence, a behavioral termination visit questionnaire was developed after early closure of the oral tenofovir and vaginal gel arms. We hypothesized that participants would be more forthcoming about nonuse after they exited the trial than during monthly/quarterly follow-up visits. Comparison of adherence reporting at routine follow-up visits with reporting at trial termination, however, indicates that disclosure of product nonadherence did not increase at the termination visit as anticipated. In resource-limited settings where women value the ancillary benefits provided by trial participation and are concerned that disclosure of nonuse may jeopardize trial participation, objective measures of adherence may yield more meaningful data regarding the inability or reluctance to use than measures of product use derived from self-report. PMID- 26906024 TI - Crysalis: an integrated server for computational analysis and design of protein crystallization. AB - The failure of multi-step experimental procedures to yield diffraction-quality crystals is a major bottleneck in protein structure determination. Accordingly, several bioinformatics methods have been successfully developed and employed to select crystallizable proteins. Unfortunately, the majority of existing in silico methods only allow the prediction of crystallization propensity, seldom enabling computational design of protein mutants that can be targeted for enhancing protein crystallizability. Here, we present Crysalis, an integrated crystallization analysis tool that builds on support-vector regression (SVR) models to facilitate computational protein crystallization prediction, analysis, and design. More specifically, the functionality of this new tool includes: (1) rapid selection of target crystallizable proteins at the proteome level, (2) identification of site non-optimality for protein crystallization and systematic analysis of all potential single-point mutations that might enhance protein crystallization propensity, and (3) annotation of target protein based on predicted structural properties. We applied the design mode of Crysalis to identify site non-optimality for protein crystallization on a proteome-scale, focusing on proteins currently classified as non-crystallizable. Our results revealed that site non-optimality is based on biases related to residues, predicted structures, physicochemical properties, and sequence loci, which provides in-depth understanding of the features influencing protein crystallization. Crysalis is freely available at http://nmrcen.xmu.edu.cn/crysalis/. PMID- 26906025 TI - Baseline HCV Antibody Prevalence and Risk Factors among Drug Users in China's National Methadone Maintenance Treatment Program. AB - BACKGROUND: Hepatitis C virus (HCV) is the most common viral infection among injecting drug users worldwide. We aimed to assess HCV antibody prevalence and associated risk factors among clients in the Chinese national methadone maintenance treatment (MMT) program. METHODS: Data from 296,209 clients who enrolled in the national MMT program between March 2004 and December 2012 were analyzed to assess HCV antibody prevalence, associated risk factors, and geographical distribution. RESULTS: Anti-HCV screening was positive for 54.6% of clients upon MMT entry between 2004 and 2012. HCV antibody prevalence at entry declined from 66.8% in 2005 to 45.9% in 2012. The most significant predictors of HCV seropositivity were injecting drug use (adjusted odds ratio [AOR]: 8.34, 95% confidence interval [CI]: 8.17-8.52, p<0.0001) and a history of drug use >=9 years (AOR: 2.01, 95% CI: 1.96-2.06, p<0.0001). Being female, of Uyghur or Zhuang ethnicity, and unmarried were identified as demographic risk factors (all p values<0.0001). Of the 28 provincial-level divisions included in the study, we found that 5 divisions had HCV antibody prevalence above 70% and 20 divisions above 50%. The HCV screening rate within 6 months after MMT entry greatly increased from 30.4% in 2004 to 93.1% in 2012. CONCLUSIONS: The current HCV antibody prevalence remains alarmingly high among MMT clients throughout most provincial-level divisions in China, particularly among injecting drug users and females. A comprehensive prevention strategy is needed to control the HCV epidemic among MMT clients in China. PMID- 26906026 TI - Obesity, Metabolic Syndrome and Nutrition. PMID- 26906027 TI - Membrane-anchored proteases in endothelial cell biology. AB - PURPOSE OF REVIEW: The endothelial cell plasma membrane is a metabolically active, dynamic, and fluid microenvironment where pericellular proteolysis plays a critical role. Membrane-anchored proteases may be expressed by endothelial cells as well as mural cells and leukocytes with distribution both inside and outside of the vascular system. Here, we will review the recent advances in our understanding of the direct and indirect roles of membrane-anchored proteases in vascular biology and the possible conservation of their extravascular functions in endothelial cell biology. RECENT FINDINGS: Membrane-anchored proteases belonging to the serine or metalloprotease families contain amino-terminal or carboxy-terminal domains, which serve to tether their extracellular protease domains directly at the plasma membrane. This architecture enables protease function and substrate repertoire to be regulated through dynamic localization in distinct areas of the cell membrane. These proteases are proving to be key components of the cell machinery for regulating vascular permeability, generation of vasoactive peptides, receptor tyrosine kinase transactivation, extracellular matrix proteolysis, and angiogenesis. SUMMARY: A complex picture of the interdependence between membrane-anchored protease localization and function is emerging that may provide a mechanism for precise coordination of extracellular signals and intracellular responses through communication with the cytoskeleton and with cellular signaling molecules. PMID- 26906028 TI - Pulling on my heartstrings: mechanotransduction in cardiac development and function. AB - PURPOSE OF REVIEW: Endothelial cells line the surface of the cardiovascular system and display a large degree of heterogeneity due to developmental origin and location. Despite this heterogeneity, all endothelial cells are exposed to wall shear stress (WSS) imparted by the frictional force of flowing blood, which plays an important role in determining the endothelial cell phenotype. Although the effects of WSS have been greatly studied in vascular endothelial cells, less is known about the role of WSS in regulating cardiac function and cardiac endothelial cells. RECENT FINDINGS: Recent advances in genetic and imaging technologies have enabled a more thorough investigation of cardiac hemodynamics. Using developmental models, shear stress sensing by endocardial endothelial cells has been shown to play an integral role in proper cardiac development including morphogenesis and formation of the conduction system. In the adult, less is known about hemodynamics and endocardial endothelial cells, but a clear role for WSS in the development of coronary and valvular disease is increasingly appreciated. SUMMARY: Future research will further elucidate a role for WSS in the developing and adult heart, and understanding this dynamic relationship may represent a potential therapeutic target for the treatment of cardiomyopathies. PMID- 26906029 TI - Efficacy and safety of skeletonized mesh implants for advanced pelvic organ prolapse: 12-month follow-up. AB - OBJECTIVE: To evaluate the efficacy and safety of skeletonized mesh implants for advanced pelvic organ prolapse (POP). METHODS: Women with advances POP underwent repair of stage III or greater anterior or posterior and apical compartment prolapse using skeletonized mesh implants (Seratom PA MR MN((r)) system-SERAG WIESSNER, Naila, Germany). Anatomical outcomes were assessed using pelvic organ prolapse quantification staging and functional outcomes were self-reported by the patients at 6 weeks, 6 and 12 months. Anatomical and functional cure rates, post operative pain and dyspareunia as well as intra and post-operative complications were reported. Success was defined as a composite of no bulge symptoms and no prolapse beyond the hymenal ring. RESULTS: At 12 months, data were available for 103 of the 105 patients originally recruited. Intra-operative complications included 2 (2 %) cases of cystotomy that were corrected vaginally. The immediate post-operative complications included 1 patient (1 %) with UTI, 4 (3.9 %) cases of self-resolved hematomas, and 6 (5.8 %) cases of bladder outlet obstruction. At 12 months, a high success rate and low complication rate was noted. Recurrence of prolapse was reported by 7 (6.6 %) patients. However, only 4 (3.8 %) underwent a repeat procedure. Two patient developed de novo SUI, and 6 (5.7 %) developed dyspareunia. No cases of mesh erosion/extrusion were noted. CONCLUSION: The present study showed excellent anatomical and quality of life results in patients with advanced POP treated with a skeletonized and reduced mesh system. No mesh exposure was recorded within the first year after surgery. PMID- 26906030 TI - Prognostic value of urinary cytology and other biomarkers for recurrence and progression in bladder cancer: a prospective study. AB - PURPOSE: Urinary cytology (C) and cystoscopy remain the gold standard for the detection and screening of bladder cancer (BC). In this prospective study, we analyzed whether baseline C, ImmunoCyt (I), BTA Stat (B), hemoglobin dipstick (H), and NMP22 BladderChek (N) can predict recurrence and progression. METHODS: Urinary samples from 91 patients with BC were prospectively collected over an 18 month period. Baseline characteristics of the population included patient demographics, various clinicopathological variables and use of intravesical therapy. Progression and recurrence were then assessed after a median follow-up of 48 months (IQR 23.7-59.5). Univariate and multivariate analyses were performed using COX proportional hazards models. RESULTS: On univariate analysis, C (HR 1.36; p = 0.26), I (HR 0.89; p = 0.66), B (HR 0.80; p = 0.42), H (HR 0.75; p = 0.30), and N (HR 0.82; p = 0.48) were not associated with recurrence-free survival (RFS). With regard to progression-free survival (PFS), C was significantly prognostic (HR 2.67; p = 0.017), whereas I, B, H, and N were not. On multivariable analysis, NMP22 was the only marker to be independently associated with RFS (HR 0.41, p < 0.01) and PFS (HR 0.32, p = 0.02). CONCLUSION: Based on the results of this study, baseline C, B, I, and H were not independently prognostic. Prognostic impact of NMP22 requires further validation in a multicenter larger study. PMID- 26906031 TI - Poor standard mp-MRI and routine biopsy fail to precisely predict intraprostatic tumor localization. AB - PURPOSE: To evaluate the localization accuracy of routinely performed preoperative multiparametric MRI (mp-MRI), not being assessed according to PI RADS criteria. METHODS: One hundred and six patients underwent radical retropubic prostatectomy (January 2011-June 2012) with preoperative MRI. Intraprostatic tumor localization suggested by mp-MRI was correlated to both biopsy and histopathology results. RESULTS: Sensitivity and specificity were as low as 25-62 and 60-94 %, respectively. Neither higher field force nor the use of an endorectal coil could enhance accuracy. There was no statistically significant concordance in any sextant. The mean number of correctly identified sextants was between 3.11 and 4.00 and, thus, insignificantly above the value of 3 that one would obtain by tossing the coin. For transrectal biopsies, sensitivity and specificity of tumor localization were 52-63 and 46-80 %, respectively. CONCLUSIONS: Neither routinely performed "non-PI-RADS" MRI nor transrectal biopsy can accurately localize prostate cancer. Focal therapy concepts rely on a precise intraprostatic tumor detection and therefore inevitably require PI-RADS assessment by radiologists with genitourinary specialization. Regarding patient discomfort and costs, "non-PI-RADS" MRIs of the prostate are not justified. PMID- 26906033 TI - Effects of Blood Pressure Lowering With Different Antihypertensive Agents on Cognitive Function and Plasma Brain-derived Neurotrophic Factor Levels: A Comparative Study. AB - PURPOSE: Hypertension is a risk factor for cognitive impairment (CI). However, the specific effect of antihypertensive therapy on cognitive function is still controversial. We aimed to investigate the effect of antihypertensive agents targeting the renin-angiotensin system (RAS) on CI and brain-derived neurotropic factor (BDNF). METHODS: We included 62 patients who had been using the same antihypertensive agent for at least 3 months. Patients who had relevant conditions that could contribute to CI were excluded. After subjects were divided into 3 groups according to their current antihypertensive medication, the cognitive status of each patient was assessed by the mini-mental state examination (MMSE). BDNF and plasma renin activity were evaluated. RESULTS: There was a negative association between systolic blood pressure and MMSE independent of medication (rho = -0.251, P = 0.049). There was no significant correlation between MMSE and BDNF. The MMSE score was slightly higher in the non-RAS group, but the difference did not reach statistical significance (P = 0.09). There was also no significant difference in BDNF levels between study groups (P = 0.32). Mean plasma renin activity levels were significantly lower in the non-RAS group compared with the angiotensin converting enzyme inhibitor and angiotensin receptor blocker groups (P = 0.007). CONCLUSIONS: We suggest that the essential intervention for CI in hypertensive patients is appropriate for blood pressure control. PMID- 26906032 TI - Protective V127 prion variant prevents prion disease by interrupting the formation of dimer and fibril from molecular dynamics simulations. AB - Recent studies uncovered a novel protective prion protein variant: V127 variant, which was reported intrinsically resistant to prion conversion and propagation. However, the structural basis of its protective effect is still unknown. To uncover the origin of the protective role of V127 variant, molecular dynamics simulations were performed to explore the influence of G127V mutation on two key processes of prion propagation: dimerization and fibril formation. The simulation results indicate V127 variant is unfavorable to form dimer by reducing the main chain H-bond interactions. The simulations of formed fibrils consisting of beta1 strand prove V127 variant will make the formed fibril become unstable and disorder. The weaker interaction energies between layers and reduced H-bonds number for V127 variant reveal this mutation is unfavorable to the formation of stable fibril. Consequently, we find V127 variant is not only unfavorable to the formation of dimer but also unfavorable to the formation of stable core and fibril, which can explain the mechanism on the protective role of V127 variant from the molecular level. Our findings can deepen the understanding of prion disease and may guide the design of peptide mimetics or small molecule to mimic the protective effect of V127 variant. PMID- 26906034 TI - Interleukin-1 Blockade in Acute Decompensated Heart Failure: A Randomized, Double Blinded, Placebo-Controlled Pilot Study. AB - BACKGROUND: Heart failure is an inflammatory disease. Patients with acute decompensated heart failure (ADHF) exhibit significant inflammatory activity on admission. We hypothesized that Interleukin-1 blockade, with anakinra (Kineret, Swedish Orphan Biovitrum), would quench the acute inflammatory response in patients with ADHF. METHODS: We randomized 30 patients with ADHF, reduced left ventricular ejection fraction (<40%), and elevated C reactive protein (CRP) levels (>=5 mg/L) to either anakinra 100 mg twice daily for 3 days followed by once daily for 11 days or matching placebo, in a 1:1 double blinded fashion. We measured daily CRP plasma levels using a high-sensitivity assay during hospitalization and then again at 14 days and evaluated the area-under-the-curve and interval changes (delta). RESULTS: Treatment with anakinra was well tolerated. At 72 hours, anakinra reduced CRP by 61% versus baseline, compared with a 6% reduction among patients receiving placebo (P = 0.004 anakinra vs. placebo). CONCLUSIONS: Interleukin-1 blockade with anakinra reduces the systemic inflammatory response in patients with ADHF. Further studies are warranted to determine whether this anti-inflammatory effect translates into improved clinical outcomes. PMID- 26906035 TI - Even a "pigtail" distal end catheter can enter the epidural space after continuous paravertebral block. AB - A woman with a medical history of breast cancer presented with chronic pain of the right hemithorax. To alleviate pain, a continuous paravertebral block was performed using a pigtail end catheter, introduced using ultrasound visualization (transversal technique at the inferior articular process of T6). Complete pain relief was observed. A few hours later, urinary retention was diagnosed and discharge from the ambulatory setting was canceled. On the following day, a new injection of local anesthetics through the catheter triggered paresthesia in the contralateral leg and a new urinary retention was diagnosed. A CT scan confirmed the epidural misplacement of the catheter. The latter was withdrawn, and the patient was released to home after the complete disappearance of her neurological symptoms. This case report highlights the risk of inadvertently misplacing the catheter into the epidural space during thoracic paravertebral block, even with a "pigtail" distal end type of catheter. PMID- 26906036 TI - Simultaneous removal of aniline, nitrogen and phosphorus in aniline-containing wastewater treatment by using sequencing batch reactor. AB - The high removal efficiencies of traditional biological aniline-degrading systems always lead to accumulation of ammonium. In this study, simultaneous removal of aniline, nitrogen and phosphorus in a single sequencing batch reactor was achieved by using anaerobic/aerobic/anoxic (A/O/A) operational process. The removal efficiencies of COD, NH4(+)-N, TN, TP were over 95.80%, 83.03%, 87.13%, 90.95%, respectively in most cases with 250mgL(-1) of initial aniline at 6h cycle when DO was 5.5+/-0.5mgL(-1). Aniline was able to be completely degraded when initial concentrations were less than 750mgL(-1). When DO increased, the removal rate of NH4(+)-N and TP slightly increased along with the moderate decrease of removal efficiencies of TN. The variation of HRT had obvious influence on removal performance of pollutants. The system showed high removal efficiencies of aniline, COD and nutrients during the variation of operating conditions, which might contribute to disposal of aniline-rich industrial wastewater. PMID- 26906040 TI - Unique anisotropic optical properties of a highly stable metal-organic framework based on trinuclear iron(iii) secondary building units linked by tetracarboxylic linkers with an anthracene core. AB - A highly stable metal-organic framework, [{Fe3(ACTBA)2}X.6DEF]n (1; X = monoanion), based on trinuclear iron(iii) secondary building units connected by tetracarboxylates with an anthracene core, 2,6,9,10-tetrakis(p carboxylatophenyl)anthracene (ACTBA), is reported. Depending on the direction of light polarisation, crystals of 1 exhibit anisotropic optical properties with birefringence Deltan = 0.3 (lambda = 590 nm). PMID- 26906041 TI - Spatial and temporal analysis of tuberculosis in Zhejiang Province, China, 2009 2012. AB - BACKGROUND: Tuberculosis (TB) is an infectious disease of major public health concern. The disease has demonstrated large space-time variations. This study aims to explore the space-time dynamics of TB cases in an economically and geographically dynamic province in China with specific references of TB control for policy makers. METHODS: Data on all reported TB cases from 2009 to 2012 were collected from the TB program at the Zhejiang Provincial Center for Disease Control and Prevention. We employed time series and exploratory spatial data analyses, including Moran's I, Local Getis's G i (*) , and Kulldorff's space-time scan statistics, to identify the temporal trends and spatial patterns of TB at a county level. RESULTS: A total of 147,941 TB cases were reported during 2009-2012 in Zhejiang. A higher proportion of TB cases were younger, male, and registered permanent residents among all TB cases notified in the province. TB cases were reported most frequently in April with small peaks in June, July, and October. This disease was spatially clustering with Moran's I values ranged from 0.29 to 0.32 (p < 0.001). A most likely cluster and ten secondary clusters were identified, mainly concentrated in the southeast and west counties of the province. CONCLUSIONS: This study identified seasonal patterns and significant space-time clusters of TB cases in Zhejiang, China. Poverty, migration, and seasonal effects may play important roles in potential clusters. PMID- 26906039 TI - Impact on clinical practice of the implementation of guidelines for the toxicity management of targeted therapies in kidney cancer. The protect-2 study. AB - BACKGROUND: The impact of such recommendations after their implementation of guidelines has not usually been evaluated. Herein, we assessed the impact and compliance with the Spanish Oncology Genitourinary Group (SOGUG) Guidelines for toxicity management of targeted therapies in metastatic renal cell carcinoma (mRCC) in daily clinical practice. METHODS: Data on 407 mRCC patients who initiated first-line targeted therapy during the year before and the year after publication and implementation of the SOGUG guideline program were available from 34 Spanish Hospitals. Adherence to SOGUG Guidelines was assessed in every cycle. RESULTS: Adverse event (AE) management was consistent with the Guidelines as a whole for 28.7% out of 966 post-implementation cycles compared with 23.1% out of 892 pre-implementation cycles (p = 0.006). Analysis of adherence by AE in non compliant cycles showed significant changes in appropriate management of hypertension (33% pre-implementation vs. 44.5% post-implementation cycles; p < 0.0001), diarrhea (74.0% vs. 80.5%; p = 0.011) and dyslipemia (25.0% vs. 44.6%; p < 0.001). CONCLUSIONS: Slight but significant improvements in AE management were detected following the implementation of SOGUG recommendations. However, room for improvement in the management of AEs due to targeted agents still remains and could be the focus for further programs in this direction. PMID- 26906042 TI - Knowledge of binge eating disorder: a cross-sectional survey of physicians in the United States. AB - OBJECTIVES: Binge eating disorder (BED)--now a designated disorder in the DSM-5- is the most prevalent eating disorder (ED), affecting 2-3% of the US population. This survey of US physicians assesses how BED is diagnosed, treated and referred. METHODS: Internists, family practitioners, obstetrics/gynecologist (OB/GYNs) and psychiatrists were randomly selected from a nationally-representative panel. Participants completed an online survey and reviewed case vignettes consistent with DSM-5-defined BED, then answered questions to elicit whether they would assess for psychiatric conditions including EDs. Those reporting they would screen and who correctly identified BED in vignettes received additional questions about BED diagnosis, treatment, and referral patterns. RESULTS: Of 278 physicians surveyed, 96% were board-certified and 87% had practiced >10 years. 23% were psychiatrists, 27% family practitioners, 31% internists and 19% OB/GYNs. 92% were 'somewhat likely' to screen for ED after reviewing DSM-5-consistent vignettes. 206 (74%) correctly identified BED. Of these, 33% and 68% reported they proactively screen eating habits for all patients and obese patients, respectively. 10% reported not screening eating habits even in the presence of ED symptoms. Fewer than half reported using DSM criteria in Diagnosing BED, and 56 (27%) did not recognize BED to be a discreet ED. CONCLUSION: Although ED awareness is improving, understanding BED as a distinct ED is lacking, which may result in low rates of screening and diagnosis. This study illustrates how taking a complete patient history (including probing BED characteristics) may be an effective first-line strategy for clinicians to facilitate optimal care for these patients. PMID- 26906044 TI - [Not Available]. AB - Ebola and MERS are contagious diseases with high mortality, and separate handling of blood samples in the laboratory is necessary. Most people who arrive in Sweden with suspicious symptoms will likely have other diseases than Ebola/MERS, for example malaria or pneumococci, but we still need to take care of these patients and be able to provide optimal treatment of electrolyte disturbances, kidney failure, bleedings etc. In this report, we describe how we solved the problem in Skane, where we built a security laboratory within the facilities of Clinical Chemistry in Malmo. Here we can now analyze malaria, blood gases, cell counts, PK value, liver status, pneumococci and legionella as well as perform routine pre transfusion testing. We describe the different point-of-care instruments that are used in the laboratory and the reasoning behind our choices, as well as challenges that we encountered on the way. PMID- 26906043 TI - Identification of hospital patients in need of palliative care--a predictive score. AB - BACKGROUND: Palliative care was initially developed for patients with advanced cancer. Over the past years, however, palliative care has broadened its focus from terminal cancer patients to patients with other serious, life-limiting illnesses. Nevertheless, the identification of palliative care needs (PCNs) among hospital patients remains an insufficiently investigated topic of research. The aim of our study was to describe the characteristics of hospital patients with palliative care needs and to develop a score for their identification. METHODS: We conducted an epidemiological study. Data were collected prospectively from inpatients at the University Medical Center Freiburg, Germany. For each patient discharged from a hospital ward, the treating physician had to report whether the patient had PCNs or not. The response rate was 96%, and data from 39,849 patients could be analyzed. A binary logistic regression analysis was performed in order to identify risk factors for developing PCNs and to develop a predictive score for the identification of patients with PCNs upon their admission to the hospital. In order to validate the risk prediction model, we used a bootstrap analysis. RESULTS: During the study period, 6.9% (2757) of all patients had palliative care needs. Only 56 of them (2%) received palliative treatment. Binary logistic regression analysis showed that older patients without relatives who suffered from metastatic cancer and/or liver cirrhosis had the highest risk of developing palliative care needs (PCN-score; sensitivity: 0.815; specificity: 0.640). CONCLUSIONS: Given the aging population and associated increase in the number of patients requiring palliative care, it is crucial to detect palliative care needs in hospital patients with both cancerous and non-cancerous life limiting diseases. Our predictive score contributes to the identification of palliative care needs in patients with life-limiting diseases, which allows physicians to take the appropriate therapeutic steps. PMID- 26906046 TI - [Not Available]. PMID- 26906045 TI - [Stop stigmatizing alcohol problems]. PMID- 26906048 TI - [Not Available]. PMID- 26906047 TI - [The AllTrials campaign and why we need Cochrane in Sweden]. PMID- 26906050 TI - [Not Available]. PMID- 26906049 TI - [Was the boat packed with hemochromatosis?]. PMID- 26906051 TI - [No evidence for routine rectal palpation in acute abdomen]. PMID- 26906053 TI - [Not Available]. PMID- 26906052 TI - [Junior physicians' temporary positions should be assigned in an open and meritocratic way]. PMID- 26906054 TI - [Not Available]. PMID- 26906055 TI - [Not Available]. PMID- 26906056 TI - [Physicians' organizations should criticize new asylum regulations]. PMID- 26906057 TI - Death receptor 6 is a novel plasmacytoid dendritic cell-specific receptor and modulates type I interferon production. PMID- 26906058 TI - Parenting Profiles and Adolescent Dating Relationship Abuse: Attitudes and Experiences. AB - Parenting behaviors such as monitoring and communications are known correlates of abusive outcomes in adolescent dating relationships. This longitudinal study draws on separate parent (58 % female; 61 % White non-Hispanic, 12 % Black non Hispanic, 7 % other non-Hispanic, and 20 % Hispanic) and youth (ages 12-18 years; 48 % female) surveys from the nationally representative Survey of Teen Relationships and Intimate Violence. Latent class analyses were applied to investigate whether there are distinguishable parenting profiles based on six measures of parent-youth relationship and interactions, with youth's attitudes about abusive dating behavior and both perpetration and victimization examined in a follow-up survey as distal outcomes (n = 1117 parent-youth dyads). A three class model-a "Positive Parenting" class, a "Strict/Harsh Parenting" class, and a "Disengaged/Harsh Parenting" class-was selected to best represent the data. The selected latent class model was conditioned on parents' (anger trait, relationship quality, attitudes about domestic violence) and youth's (prior victimization and perpetration) covariates, controlling for parent's gender, race/ethnicity, income, marital status, and youth's age and gender. Youth in the "Positive Parenting" class were significantly less likely 1 year later to be tolerant of violence against boyfriends under any conditions as well as less likely to perpetrate adolescent relationship abuse or to be a victim of adolescent relationship abuse. Parents' anger and relationship quality and youth's prior perpetration of adolescent relationship abuse as well as gender, age, and race/ethnicity predicted class membership, informing universal prevention program and message design, as well as indicated efforts to target communications and services for parents as well as for youth. PMID- 26906059 TI - C. elegans as a model organism for human mitochondrial associated disorders. AB - Mitochondria are small cytoplasmic organelles whose most important function is to provide the energy required by our cells and organism to live. To maintain an adequate mitochondrial homeostasis cells possess numerous mitochondrial quality controls and protective compensatory pathways, which can be activated to cope with a certain degree of mitochondrial dysfunction. However, when the mitochondrial damage is too severe and these defensive mechanisms are not anymore sufficient to deal with it, pathological signs arise. In the past few decades numerous genetic disorders ascribed to severe mitochondrial defects have been recognized with variable onset and symptomatology ranging from neuromuscular degeneration to cancer syndromes. Unfortunately, to date, only symptomatic and no curative therapies exist for most of these devastating, life-threatening disorders. Model organisms, and especially the nematode Caenorhabditis elegans, with its sequenced and highly conserved genome, and a simple but well characterized nervous system, have enormously contributed in the past years to gain insight into the pathogenesis and treatment of different diseases. Here, we will summarize some of the advantages offered by the nematode system to model neurodegenerative diseases associated with mitochondrial electron transport chain defects and screen for therapeutic interventions. PMID- 26906061 TI - 2D Representation of Transcriptomes by t-SNE Exposes Relatedness between Human Tissues. AB - The GTEx Consortium reported that hierarchical clustering of RNA profiles from 25 unique tissue types among 1641 individuals accurately distinguished the tissue types, but a multidimensional scaling failed to generate a 2D projection of the data that separates tissue-subtypes. In this study we show that a projection by t Distributed Stochastic Neighbor Embedding is in line with the cluster analysis which allows a more detailed examination and visualization of human tissue relationships. PMID- 26906060 TI - Maintaining physical activity during refeeding improves body composition, intestinal hyperpermeability and behavior in anorectic mice. AB - A role of gut-brain axis emerges in the pathophysiology of anorexia nervosa and maintaining adapted physical activity during refeeding remains discussed. We aimed to assess gastrointestinal protein metabolism and investigate the contribution of physical activity during refeeding in C57BL/6 mice with activity based anorexia (ABA). ABA mice exhibited lower body weight and food intake with increase of lean mass/fat mass ratio and fat oxidation. Colonic permeability was increased in ABA. Ad libitum food access was then restored and ABA group was divided into two subgroups, with access to running wheel (ABA-PA) or not (ABA NPA). After refeeding, fat free mass was completely restored only in ABA-PA. Colonic permeability was enhanced in ABA-NPA. Finally, muscle kynurenine conversion into kynurenic acid was lower in ABA-NPA who also exhibited altered behavior. Maintaining physical activity during refeeding may thus limit colonic hyperpermeability and improve behavior in anorectic mice. PMID- 26906063 TI - Rituximab in lupus nephritis: A non-systematic review. AB - Lupus nephritis (LN) is a common and severe complication in patients with lupus. Current therapy is based on immunosuppressive drugs and glucocorticoids. Recently, rituximab has been proposed as an alternative treatment for LN. Rituximab is a monoclonal antibody directed against the CD20 antigen receptor on B cells. The aim of this review is to summarize all the available information about rituximab in LN. Eleven studies were found; three of them were observational studies (2 prospective and 1 retrospective) and eight were clinical trials (7 open-label studies and only 1 randomized controlled trial [RCT]). The evidence is insufficient to establish the role of rituximab in the treatment of LN. Results from the only RCT, which were negative, suggest a clinical benefit in black people. Further studies must confirm this hypothesis. Controlled clinical trials involving adaptive randomization are required to establish the real benefit of rituximab in LN. PMID- 26906062 TI - The expression of the chemokine receptor CCR5 in tick-borne encephalitis. AB - BACKGROUND: Chemokine receptor 5 (CCR5) is hypothesized to drive the lymphocyte migration to central nervous system in flavivirus encephalitis, and the non functional CCR5Delta32 genetic variant was identified as a risk factor of a West Nile virus infection and of tick-borne encephalitis (TBE). We have attempted to investigate how CCR5 expression corresponds to the clinical course and severity of TBE. METHODS: We have repeatedly studied CCR5 expression in 76 patients during encephalitic and convalescent TBE phase, analyzing its association with clinical features, cerebrospinal fluid (csf) pleocytosis, and concentrations of CCR5 ligands (chemokines CCL3, CCL4, and CCL5) and CCR5 genotype. Fifteen patients with neuroborreliosis, 7 with aseptic meningitis, 17 in whom meningitis/encephalitis had been excluded, and 18 healthy blood donors were studied as controls. Expression of CCR5 was measured cytometrically in blood and csf-activated Th lymphocytes (CD3+CD4+CD45RO+). Concentrations of chemokines in serum and csf were measured immunoenzymatically, and CCR5Delta32 was detected with sequence-specific primers. Data were analyzed with non-parametric tests, and p < 0.05 was considered significant. RESULTS: The blood expression of CCR5 did neither differ between the groups nor change in the course of TBE. The CCR5 expression in the inflammatory csf was several-fold increased in comparison with blood but lower in TBE than in neuroborreliosis. The csf concentration of CCL5 was increased in TBE, the highest in the most severe presentation (meningoencephalomyelitis) and correlated with pleocytosis. The CCR5Delta32/wt genotype present in 7 TBE patients was associated with a decreased CCR5 expression, but enrichment of csf Th population in CCR5-positive cells and the intrathecal inflammatory response were preserved, without a compensatory increase of CCL5 expression. CONCLUSIONS: We infer CCR5 and CCL5 participate in the response to TBE virus, as well as to other neurotropic pathogens. The intrathecal response to TBE is not hampered in the bearers of a single copy of CCR5Delta32 allele, suggesting that the association of CCR5Delta32 with TBE may be mediated in the periphery at the earlier stage of the infection. Otherwise, a variability of the CCR5 expression in the peripheral blood lymphocytes seems not to be associated with a variable susceptibility to TBE. PMID- 26906064 TI - 2-(Naphthalen-1-yl)thiophene as a New Motif for Porphyrinoids: Meso-Fused Carbaporphyrin. AB - The first synthesis of meso-fused carbaporphyrin via a premodification method was accomplished by substituting two pyrrole moieties and one meso-carbon with 2 (naphthalen-1-yl)thiophene. The obtained global pi-conjugation pathway of the macrocycle noticeably disturbs the 10pi local aromaticity of naphthalene, and its aromatic nature was supported by NMR spectroscopy together with nucleus independent chemical shift, anisotropy of the induced current density, and harmonic oscillator stabilization energy calculations. In addition, the meso fused carbaporphyrin also allowed the formation of a square planar Pd(II) complex. PMID- 26906065 TI - Effects of Noninhibitory Serpin Maspin on the Actin Cytoskeleton: A Quantitative Image Modeling Approach. AB - Recent developments in quantitative image analysis allow us to interrogate confocal microscopy images to answer biological questions. Clumped and layered cell nuclei and cytoplasm in confocal images challenges the ability to identify subcellular compartments. To date, there is no perfect image analysis method to identify cytoskeletal changes in confocal images. Here, we present a multidisciplinary study where an image analysis model was developed to allow quantitative measurements of changes in the cytoskeleton of cells with different maspin exposure. Maspin, a noninhibitory serpin influences cell migration, adhesion, invasion, proliferation, and apoptosis in ways that are consistent with its identification as a tumor metastasis suppressor. Using different cell types, we tested the hypothesis that reduction in cell migration by maspin would be reflected in the architecture of the actin cytoskeleton. A hybrid marker controlled watershed segmentation technique was used to segment the nuclei, cytoplasm, and ruffling regions before measuring cytoskeletal changes. This was informed by immunohistochemical staining of cells transfected stably or transiently with maspin proteins, or with added bioactive peptides or protein. Image analysis results showed that the effects of maspin were mirrored by effects on cell architecture, in a way that could be described quantitatively. PMID- 26906067 TI - [Purpura and arthritis: Is it always Henoch-Schonlein purpura?] PMID- 26906066 TI - A call for new standard of care in perioperative gynecologic oncology practice: Impact of enhanced recovery after surgery (ERAS) programs. AB - Enhanced recovery after surgery (ERAS) programs aim to hasten functional recovery and improve postoperative outcomes. However, there is a paucity of data on ERAS programs in gynecologic surgery. We reviewed the published literature on ERAS programs in colorectal surgery, general gynecologic surgery, and gynecologic oncology surgery to evaluate the impact of such programs on outcomes, and to identify key elements in establishing a successful ERAS program. ERAS programs are associated with shorter length of hospital stay, a reduction in overall health care costs, and improvements in patient satisfaction. We suggest an ERAS program for gynecologic oncology practice involving preoperative, intraoperative, and postoperative strategies including; preadmission counseling, avoidance of preoperative bowel preparation, use of opioid-sparing multimodal perioperative analgesia (including loco-regional analgesia), intraoperative goal-directed fluid therapy (GDT), and use of minimally invasive surgical techniques with avoidance of routine use of nasogastric tube, drains and/or catheters. Postoperatively, it is important to encourage early feeding, early mobilization, timely removal of tubes and drains, if present, and function oriented multimodal analgesia regimens. Successful implementation of an ERAS program requires a multidisciplinary team effort and active participation of the patient in their goal-oriented functional recovery program. However, future outcome studies should evaluate the efficacy of an intervention within the pathway, include objective measures of symptom burden and control, study measures of functional recovery, and quantify outcomes of the program in relation to the rates of adherence to the key elements of care in gynecologic oncology such as oncologic outcomes and return to intended oncologic therapy (RIOT). PMID- 26906068 TI - Upregulation of Long Non-Coding RNA PlncRNA-1 Promotes Metastasis and Induces Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma. AB - BACKGROUND/AIMS: PlncRNA-1 has been demonstrated to promote malignancy in various cancers. The present study aims to investigate the expression pattern, prognosis value and the function of PlncRNA-1 in human hepatocellular carcinoma (HCC). METHODS: The expression of PlncRNA-1 in 84 pairs of HCC and their matched normal tissues was examined by quantitative real-time polymerase chain reaction (qRT PCR). The correlations of PlncRNA-1 expression and clinicopathological characteristics and prognosis were also analyzed. The biological role of PlncRNA 1 in cell proliferation, migration and invasion was examined in vitro and in vivo. RESULTS: The results showed that the level of PlncRNA-1 expression was significantly increased in HCC tissues and significantly correlated with tumor size, vascular invasion and advanced TNM stage. Moreover, patients with high levels of PlncRNA-1 expression had relatively poor prognostic outcomes, serving as an independent prognostic factor for HCC. In vitro functional assays indicated that knockdown of PlncRNA-1 expression significantly reduced cell proliferation, migration and invasion by inhibiting the epithelial-mesenchymal transition (EMT) signaling. Animal model experiments confirmed the ability of PlncRNA-1 to promote tumor growth in vivo. CONCLUSIONS: Taken together, our findings suggest that PlncRNA-1 may serve as an oncogene in HCC progression and represent a valuable prognostic marker and potential therapeutic target for HCC. PMID- 26906069 TI - Positioning the breathing but unresponsive patient: what is the evidence? PMID- 26906071 TI - Voice problems in school-aged children following very preterm birth. AB - BACKGROUND AND OBJECTIVE: Very preterm children may be at risk of voice abnormalities (dysphonia). Risk factors previously identified in extremely preterm children include female gender, multiple intubations, complicated intubation and very low birth weight. This study sought to identify the prevalence of dysphonia in very preterm children, at school age. METHODS: Children born between 23 and 32 weeks' gestation were included in this prospective observational study. Participants were randomly selected from a sample stratified by gestational age and number of intubations, and were aged between 5 and 12 years at the time of assessment. Clinical voice assessments were conducted by a speech pathologist, and a diagnosis of dysphonia was made based on the presence and severity of disturbance to the voice. Retrospective chart review identified medical and demographic characteristics. RESULTS: 178 participants were assessed. The prevalence of dysphonia in this cohort was 61%. 31% presenting with significant dysphonia, that is, voice disturbance of greater than mild in severity. Female gender (p=0.009), gestational age (p=0.031) and duration of intubation (p=0.021) were significantly associated with dysphonia although some preterm children with dysphonia were never intubated. CONCLUSIONS: Significant voice abnormalities were observed in children born at up to 32 weeks' gestation, with intubation a major contributing factor. TRIAL REGISTRATION NUMBER: ACTRN12613001015730. PMID- 26906073 TI - Triggering autocatalytic reaction by host-guest interactions. AB - The acceleration of a sequential reaction through electrostatic alteration of substrate basicity within a supramolecular host is demonstrated. In the presence of the host, the reaction, which is autocatalytic, starts much sooner and exhibits substrate size selectivity. PMID- 26906070 TI - Congenital laryngomalacia is related to exercise-induced laryngeal obstruction in adolescence. AB - OBJECTIVES: Congenital laryngomalacia (CLM) is the major cause of stridor in infants. Most cases are expected to resolve before 2 years of age, but long-term respiratory prospects are poorly described. We aimed to investigate if CLM was associated with altered laryngeal structure or function in later life. METHODS: Twenty of 23 (87%) infants hospitalised at Haukeland University Hospital during 1990-2000 for CLM without comorbidities and matched controls were assessed at mean age 13 years. Past and current respiratory morbidity was recorded in a questionnaire, and spirometry performed according to standard quality criteria. Laryngoscopy was performed at rest and continuously throughout a maximal treadmill exercise test (continuous laryngoscopy exercise test (CLE-test)), and scored and classified in a blinded fashion according to preset criteria. RESULTS: In the CLM group, laryngeal anatomy supporting CLM in infancy was described at rest in nine (45%) adolescents. Eleven (55%) reported breathing difficulties in relation to exercise, of whom 7 had similarities to CLM at rest and 10 had supraglottic obstruction during CLE-test. Overall, 6/20 had symptoms during exercise and similarities to CLM at rest and obstruction during CLE-test. In the control group, one adolescent reported breathing difficulty during exercise and two had laryngeal obstruction during CLE-test. The two groups differed significantly from each other regarding laryngoscopy scores, obtained at rest and during exercise (p=0.001 or less). CONCLUSIONS: CLM had left footprints that increased the risk of later exercise-induced symptoms and laryngeal obstruction. The findings underline the heterogeneity of childhood respiratory disease and the importance of considering early life factors. PMID- 26906074 TI - Gene expression patterns in transgenic mouse models of hypertrophic cardiomyopathy caused by mutations in myosin regulatory light chain. AB - Using microarray and bioinformatics, we examined the gene expression profiles in transgenic mouse hearts expressing mutations in the myosin regulatory light chain shown to cause hypertrophic cardiomyopathy (HCM). We focused on two malignant RLC mutations, Arginine 58->Glutamine (R58Q) and Aspartic Acid 166 -> Valine (D166V), and one benign, Lysine 104 -> Glutamic Acid (K104E)-mutation. Datasets of differentially expressed genes for each of three mutants were compared to those observed in wild-type (WT) hearts. The changes in the mutant vs. WT samples were shown as fold-change (FC), with stringency FC >= 2. Based on the gene profiles, we have identified the major signaling pathways that underlie the R58Q-, D166V- and K104E-HCM phenotypes. The correlations between different genotypes were also studied using network-based algorithms. Genes with strong correlations were clustered into one group and the central gene networks were identified for each HCM mutant. The overall gene expression patterns in all mutants were distinct from the WT profiles. Both malignant mutations shared certain classes of genes that were up or downregulated, but most similarities were noted between D166V and K104E mice, with R58Q hearts showing a distinct gene expression pattern. Our data suggest that all three HCM mice lead to cardiomyopathy in a mutation-specific manner and thus develop HCM through diverse mechanisms. PMID- 26906075 TI - Early oxidative damage induced by doxorubicin: Source of production, protection by GKT137831 and effect on Ca(2+) transporters in HL-1 cardiomyocytes. AB - In atrial-derived HL-1 cells, ryanodine receptor and Na(+)/Ca(2+)-exchanger were altered early by 5 MUM doxorubicin. The observed effects were an increase of cytosolic Ca(2+) at rest, ensuing ryanodine receptor phosphorylation, and the slowing of Ca(2+) transient decay after caffeine addition. Doxorubicin triggered a linear rise of reactive oxygen species (ROS) with no early effect on mitochondrial inner membrane potential. Doxorubicin and ROS were both detected in mitochondria by colocalization with fluorescence probes and doxorubicin-induced ROS was totally blocked by mitoTEMPO. The NADPH oxidase activity in the mitochondrial fraction was sensitive to inhibition by GKT137831, and doxorubicin induced ROS decreased gradually as the GKT137831 concentration added in preincubation was increased. When doxorubicin-induced ROS was prevented by GKT137831, the kinetic response revealed a permanent degree of protection that was consistent with mitochondrial NADPH oxidase inhibition. In contrast, the ROS induction by doxorubicin after melatonin preincubation was totally eliminated at first but the effect was completely reversed with time. Limiting the source of ROS production is a better alternative for dealing with oxidative damage than using ROS scavengers. The short-term effect of doxorubicin on Ca(2+) transporters involved in myocardiac contractility was dependent on oxidative damage, and so the impairment was subsequent to ROS production. PMID- 26906076 TI - The need to do and imbibe as well as debate and discuss. PMID- 26906077 TI - Headspace: The gap between the evidence and the arguments. PMID- 26906078 TI - Stimulants for depression: On the up and up? AB - The use of traditional psychostimulants (methylphenidate and dexamphetamine) and stimulant-like drugs (modafinil and armodafinil) for the treatment of depression is a growing concern given the lack of research evidence supporting their effectiveness. The current article describes the role of stimulants in treating depression--specifically their risks and benefits and their potential use alongside antidepressants. Clinically, the rapid amelioration of depressive symptoms with traditional psychostimulants is often dramatic but short-lived, and this suggests that they likely operate via different mechanisms to conventional antidepressants. More importantly, there is little evidence from randomised controlled trials supporting their efficacy in treating depression, although modafinil has been shown to be effective in reducing prominent depressive symptoms, such as fatigue. Research is urgently required to clarify psychostimulants' mechanisms of action and to evaluate their long-term benefits and risks in the treatment of major and bipolar depression. Ultimately, specificity of action needs to be determined to inform the sophisticated clinical use of psychostimulants in the management of depression. Until then they should only be prescribed if absolutely necessary, and even then their prescription should be facilitatory and time limited unless it is for investigational purposes. PMID- 26906079 TI - McGorry et al. debate on the 'National Mental Health Commission Report: Evidence based or ideologically driven?'. PMID- 26906081 TI - One-pot synthesis of single-crystal Pt nanoplates uniformly deposited on reduced graphene oxide, and their high activity and stability on the electrocalalytic oxidation of methanol. AB - We demonstrate a one-pot thermoreduction approach towards the preparation of single-crystal Pt nanoplates, which were uniformly deposited on the reduced graphene oxide (RGO) using polyvinylpyrrolidone (PVP) as a stabilizer. The size of Pt nanoplates can be tuned from 6.8 to 10.1 nm by controlling Pt loading. The as-prepared Pt/PVP/RGO catalysts show high stability and activity towards the methanol oxidation reaction (MOR). Their MOR current can reach up to 401 mA mg( 1) Pt and MOR current can maintain 89.4% of its initial value after 10 000 potential cycles. PMID- 26906083 TI - Doxorubicin-Loaded Nanobubbles Combined with Extracorporeal Shock Waves: Basis for a New Drug Delivery Tool in Anaplastic Thyroid Cancer. AB - BACKGROUND: No standard chemotherapy is available for anaplastic thyroid cancer (ATC). Drug-loaded nanobubbles (NBs) are a promising innovative anticancer drug formulation, and combining them with an externally applied trigger may further control drug release at the target region. Extracorporeal shock waves (ESWs) are acoustic waves widely used in urology and orthopedics, with no side effects. The aim of the present work was to combine ESWs and new doxorubicin-loaded glycol chitosan NBs in order to target doxorubicin and enhance its antitumor effect in ATC cell lines. METHODS: CAL-62 and 8305C cells were treated with empty NBs, fluorescent NBs, free doxorubicin, and doxorubicin-loaded NBs in the presence or in the absence of ESWs. NB entrance was evaluated by fluorescence microscopy and flow cytofluorimetry. Cell viability was assessed by Trypan Blue exclusion and WST-1 proliferation assays. Doxorubicin intracellular content was measured by high-performance liquid chromatography. RESULTS: Treatment with empty NBs and ESWs, even in combination, was safe, as cell viability and growth were not affected. Loading NBs with doxorubicin and combining them with ESWs generated the highest cytotoxic effect, resulting in drug GI50 reduction of about 40%. Mechanistically, ESWs triggered intracellular drug release from NBs, resulting in the highest nuclear drug content. CONCLUSIONS: Combined treatment with doxorubicin-loaded NBs and ESWs is a promising drug delivery tool for ATC treatment with the possibility of using lower doxorubicin doses and thus limiting its systemic side effects. PMID- 26906084 TI - Mononuclear and polynuclear complexes ligated by an iminodiacetic acid derivative: synthesis, structure, solution studies and magnetic properties. AB - Two novel families of coordination polymers, [Ln(bzlida)(Hbzlida)].H2O (Ln = La, Nd) and [Ln2(bzlida)3].3H2O (Ln = Nd, Sm, Eu, Gd) were prepared by hydrothermal reaction of Ln2O3 with benzyliminodiacetic acid (H2bzlida). The conditions of synthesis, in particular the pH value, were selected on the basis of previous speciation studies reported in this work. The first type of complex consists of 1D chains built by a fully deprotonated ligand bridging two lanthanide ions and protonated Hbzlida(-) ligands connecting three cations. The second type is formed by [Ln2(bzlida)3] bimetallic units in which the ligand has a tridentate NOO coordination mode. This is expanded to a 2D network through carboxylate linkers. Under similar synthetic conditions but including copper acetate in the reaction mixture, a new compound was also obtained and characterized: [Cu(bzlida)2{Er(AcO)(H2O)5}2][Cu(bzlida)2].6H2O (AcO = acetate). This salt is made up of the [Cu(bzlida)2{Er(AcO)(H2O)5}2](2+) heterotrimetallic complex cation containing an acetato bridge, and the [Cu(bzlida)2](2-) anion. The same reaction produces the monomeric [Cu(Hbzlida)2].4H2O whose structure was also elucidated. Magnetic properties of the Gd(iii) derivative were studied and analyzed experimentally and theoretically. The results are compared and discussed with respect to those reported in the literature and a magnetostructural correlation is suggested. PMID- 26906082 TI - Doublesex and mab-3 related transcription factor 1 (DMRT1) is a sex-specific genetic determinant of childhood-onset asthma and is expressed in testis and macrophages. AB - BACKGROUND: Asthma is a disease affecting more boys than girls in childhood and more women than men in adulthood. The mechanisms behind these sex-specific differences are not yet understood. OBJECTIVE: We analyzed whether and how genetic factors contribute to sex-specific predisposition to childhood-onset asthma. METHODS: Interactions between sex and polymorphisms on childhood asthma risk were evaluated in the Multicentre Asthma Genetics in Childhood Study (MAGICS)/Phase II International Study of Asthma and Allergies in Childhood (ISAAC II) population on a genome-wide level, and findings were validated in independent populations. Genetic fine mapping of sex-specific asthma association signals was performed, and putatively causal polymorphisms were characterized in vitro by using electrophoretic mobility shift and luciferase activity assays. Gene and protein expression of the identified gene doublesex and mab-3 related transcription factor 1 (DMRT1) were measured in different human tissues by using quantitative real-time PCR and immunohistochemistry. RESULTS: Polymorphisms in the testis-associated gene DMRT1 displayed interactions with sex on asthma status in a population of primarily clinically defined asthmatic children and nonasthmatic control subjects (lowest P = 5.21 * 10(-6)). Replication of this interaction was successful in 2 childhood populations clinically assessed for asthma but showed heterogeneous results in other population-based samples. Polymorphism rs3812523 located in the putative DMRT1 promoter was associated with allele-specific changes in transcription factor binding and promoter activity in vitro. DMRT1 expression was observed not only in the testis but also in lung macrophages. CONCLUSION: DMRT1 might influence sex-specific patterns of childhood asthma, and its expression in testis tissue and lung macrophages suggests a potential involvement in hormone or immune cell regulation. PMID- 26906085 TI - Assessing the environmental sustainability of energy recovery from municipal solid waste in the UK. AB - Even though landfilling of waste is the least favourable option in the waste management hierarchy, the majority of municipal solid waste (MSW) in many countries is still landfilled. This represents waste of valuable resources and could lead to higher environmental impacts compared to energy recovered by incineration, even if the landfill gas is recovered. Using life cycle assessment (LCA) as a tool, this paper aims to find out which of the following two options for MSW disposal is more environmentally sustainable: incineration or recovery of biogas from landfills, each producing either electricity or co-generating heat and electricity. The systems are compared on a life cycle basis for two functional units: 'disposal of 1 tonne of MSW' and 'generation of 1 kWh of electricity'. The results indicate that, if both systems are credited for their respective recovered energy and recyclable materials, energy from incineration has much lower impacts than from landfill biogas across all impact categories, except for human toxicity. The impacts of incineration co-generating heat and electricity are negative for nine out of 11 categories as the avoided impacts for the recovered energy and materials are higher than those caused by incineration. By improving the recovery rate of biogas, some impacts of landfilling, such as global warming, depletion of fossil resources, acidification and photochemical smog, would be significantly reduced. However, most impacts of the landfill gas would still be higher than the impacts of incineration, except for global warming and human toxicity. The analysis on the basis of net electricity produced shows that the LCA impacts of electricity from incineration are several times lower in comparison to the impacts of electricity from landfill biogas. Electricity from incineration has significantly lower global warming and several other impacts than electricity from coal and oil but has higher impacts than electricity from natural gas or UK grid. At the UK level, diverting all MSW currently landfilled to incineration with energy recovery would not only avoid the environmental impacts associated with landfilling but, under the current assumptions, would also meet 2.3% of UK's electricity demand and save 2-2.6 million tonnes of greenhouse gas emissions per year. PMID- 26906086 TI - Campus Sexual Assault: A Systematic Review of Prevalence Research From 2000 to 2015. AB - Sexual assault is a pervasive problem on university and college campuses in the United States that has garnered growing national attention, particularly in the past year. This is the first study to systematically review and synthesize prevalence findings from studies on campus sexual assault (CSA) published since 2000 ( n = 34). The range of prevalence findings for specific forms of sexual victimization on college campuses (i.e., forcible rape, unwanted sexual contact, incapacitated rape, sexual coercion, and studies' broad definitions of CSA/rape) is provided, and methodological strengths and limitations in the empirical body of research on CSA are discussed. Prevalence findings, research design, methodology, sampling techniques, and measures, including the forms of sexual victimization measured, are presented and evaluated across studies. Findings suggest that unwanted sexual contact appears to be most prevalent on college campuses, including sexual coercion, followed by incapacitated rape, and completed or attempted forcible rape. Additionally, several studies measured broad constructs of sexual assault that typically include combined forms of college-based sexual victimization (i.e., forcible completed or attempted rape, unwanted sexual contact, and/or sexual coercion). Extensive variability exists within findings for each type of sexual victimization measured, including those that broadly measure sexual assault, which is largely explained by differences in sampling strategies and overall study designs as well as measures of sexual assault used in studies. Implications for findings and recommendations for future research on the prevalence of college-based sexual victimization are provided. PMID- 26906087 TI - Theoretical Study of the Initial Stages of Self-Assembly of a Carboxysome's Facet. AB - Bacterial microcompartments, BMCs, are organelles that exist within wide variety of bacteria and act as nanofactories. Among the different types of known BMCs, the carboxysome has been studied the most. The carboxysome plays an important role in the light-independent part of the photosynthesis process, where its icosahedral-like proteinaceous shell acts as a membrane that controls the transport of metabolites. Although a structural model exists for the carboxysome shell, it remains largely unknown how the shell proteins self-assemble. Understanding the self-assembly process can provide insights into how the shell affects the carboxysome's function and how it can be modified to create new functionalities, such as artificial nanoreactors and artificial protein membranes. Here, we describe a theoretical framework that employs Monte Carlo simulations with a coarse-grain potential that reproduces well the atomistic potential of mean force; employing this framework, we are able to capture the initial stages of the 2D self-assembly of CcmK2 hexamers, a major protein-shell component of the carboxysome's facet. The simulations reveal that CcmK2 hexamers self-assemble into clusters that resemble what was seen experimentally in 2D layers. Further analysis of the simulation results suggests that the 2D self assembly of carboxysome's facets is driven by a nucleation-growth process, which in turn could play an important role in the hierarchical self-assembly of BMC shells in general. PMID- 26906088 TI - Testing for myositis specific autoantibodies: Comparison between line blot and immunoprecipitation assays in 57 myositis sera. AB - OBJECTIVE: To analyze the performance of a line blot assay for the identification of autoantibodies in sera of patients affected by myositis, compared with immunoprecipitation (IP) as gold standard. METHODS: 66 sera of patients with myositis (23 polymyositis, 8 anti-synthetase syndromes, 29 dermatomyositis and 6 overlap syndromes) were tested by commercial LB (Euroimmun, Lubeck, Germany); 57 sera were analyzed also by IP of K562 cell extract radiolabeled with (35)S methionine. Inter-rater agreement was calculated with Cohen's k coefficient. RESULTS: Myositis-specific antibodies (MSA) were detected in 36/57 sera (63%) by IP and in 39/66 sera (59%) by LB. The most frequent MSA found by LB were anti-Jo1 and anti-Mi2 found in 15% (10/66) of sera, followed by anti-NXP2 and anti-SRP detected in 106% (7/66) of sera. Anti-TIF1gamma and anti-MDA5 were found in 6 (9%) and 5 sera (7.6%), respectively. A good agreement between methods was found only for anti-TIF1gamma, anti-MDA5 and anti-NXP-2 antibodies, while a moderate agreement was estimated for anti-Mi2 and anti-EJ. By contrast, a high discordance rate for the detection of anti-Jo1 antibodies was evident (k: 0.3). Multiple positivity for MSA were found in 11/66 (17%) by LB and 0/57 by IP (p: 0001). Comparing the clinical features of these 11 sera, we found total discrepancies between assays in 3 sera (27.3%), a relative discrepancy due to the occurrence of one discordant autoantibody (not confirmed by IP) in 5 cases (45.5%) and a total discrepancy between LB and IP results, but with a relative concordance with clinical features were found in other 3 sera (27.3%). The semiquantitative results do not support the interpretation of the data. CONCLUSIONS: The use of LB assay allowed the detection of new MSA, such as anti-MDA5, anti-MJ and anti TIF1gamma antibodies, previously not found with routine methods. However, the high prevalence of multiple positivities and the high discondant rate of anti-Jo1 antibodies could create some misinterpretation of the results from the clinical point of view. These data should be confirmed by enlarging the number of myositis cases. PMID- 26906089 TI - Differential scanning fluorimetry based assessments of the thermal and kinetic stability of peptide-MHC complexes. AB - Measurements of thermal stability by circular dichroism (CD) spectroscopy have been widely used to assess the binding of peptides to MHC proteins, particularly within the structural immunology community. Although thermal stability assays offer advantages over other approaches such as IC50 measurements, CD-based stability measurements are hindered by large sample requirements and low throughput. Here we demonstrate that an alternative approach based on differential scanning fluorimetry (DSF) yields results comparable to those based on CD for both class I and class II complexes. As they require much less sample, DSF-based measurements reduce demands on protein production strategies and are amenable for high throughput studies. DSF can thus not only replace CD as a means to assess peptide/MHC thermal stability, but can complement other peptide-MHC binding assays used in screening, epitope discovery, and vaccine design. Due to the physical process probed, DSF can also uncover complexities not observed with other techniques. Lastly, we show that DSF can also be used to assess peptide/MHC kinetic stability, allowing for a single experimental setup to probe both binding equilibria and kinetics. PMID- 26906091 TI - Reply: Metformin for women with hyperandrogenic anovulation. PMID- 26906092 TI - Significance of (sub)clinical thyroid dysfunction and thyroid autoimmunity before conception and in early pregnancy: a systematic review. PMID- 26906093 TI - Metformin for women with hyperandrogenic anovulation. PMID- 26906090 TI - Activation of the unfolded protein response promotes axonal regeneration after peripheral nerve injury. AB - Although protein-folding stress at the endoplasmic reticulum (ER) is emerging as a driver of neuronal dysfunction in models of spinal cord injury and neurodegeneration, the contribution of this pathway to peripheral nerve damage remains poorly explored. Here we targeted the unfolded protein response (UPR), an adaptive reaction against ER stress, in mouse models of sciatic nerve injury and found that ablation of the transcription factor XBP1, but not ATF4, significantly delay locomotor recovery. XBP1 deficiency led to decreased macrophage recruitment, a reduction in myelin removal and axonal regeneration. Conversely, overexpression of XBP1s in the nervous system in transgenic mice enhanced locomotor recovery after sciatic nerve crush, associated to an improvement in key pro-regenerative events. To assess the therapeutic potential of UPR manipulation to axonal regeneration, we locally delivered XBP1s or an shRNA targeting this transcription factor to sensory neurons of the dorsal root ganglia using a gene therapy approach and found an enhancement or reduction of axonal regeneration in vivo, respectively. Our results demonstrate a functional role of specific components of the ER proteostasis network in the cellular changes associated to regeneration and functional recovery after peripheral nerve injury. PMID- 26906094 TI - Proven: The causative role of homozygous H63D mutation in hereditary haemochromatosis. PMID- 26906095 TI - Anisakis and colonic polyp, a rare association. PMID- 26906096 TI - Mechanism of biological denitrification inhibition: procyanidins induce an allosteric transition of the membrane-bound nitrate reductase through membrane alteration. AB - Recently, it has been shown that procyanidins from Fallopia spp. inhibit bacterial denitrification, a phenomenon called biological denitrification inhibition (BDI). However, the mechanisms involved in such a process remain unknown. Here, we investigate the mechanisms of BDI involving procyanidins, using the model strain Pseudomonas brassicacearum NFM 421. The aerobic and anaerobic (denitrification) respiration, cell permeability and cell viability of P. brassicacearum were determined as a function of procyanidin concentration. The effect of procyanidins on the bacterial membrane was observed using transmission electronic microscopy. Bacterial growth, denitrification, NO3- and NO2-reductase activity, and the expression of subunits of NO3- (encoded by the gene narG) and NO2-reductase (encoded by the gene nirS) under NO3 or NO2 were measured with and without procyanidins. Procyanidins inhibited the denitrification process without affecting aerobic respiration at low concentrations. Procyanidins also disturbed cell membranes without affecting cell viability. They specifically inhibited NO3- but not NO2-reductase.Pseudomonas brassicacearum responded to procyanidins by over-expression of the membrane-bound NO3-reductase subunit (encoded by the gene narG). Our results suggest that procyanidins can specifically inhibit membrane bound NO3-reductase inducing enzymatic conformational changes through membrane disturbance and that P. brassicacearum responds by over-expressing membrane-bound NO3-reductase. Our results lead the way to a better understanding of BDI. PMID- 26906097 TI - Ecological functions of Trichoderma spp. and their secondary metabolites in the rhizosphere: interactions with plants. AB - Trichodermaspp. are common soil and root inhabitants that have been widely studied due to their capacity to produce antibiotics, parasitize other fungi and compete with deleterious plant microorganisms. These fungi produce a number of secondary metabolites such as non-ribosomal peptides, terpenoids, pyrones and indolic-derived compounds. In the rhizosphere, the exchange and recognition of signaling molecules byTrichodermaand plants may alter physiological and biochemical aspects in both. For example, severalTrichodermastrains induce root branching and increase shoot biomass as a consequence of cell division, expansion and differentiation by the presence of fungal auxin-like compounds. Furthermore,Trichoderma, in association with plant roots, can trigger systemic resistance and improve plant nutrient uptake. The present review describes the most recent advances in understanding the ecological functions ofTrichodermaspp. in the rhizosphere at biochemical and molecular levels with special emphasis on their associations with plants. Finally, through a synthesis of the current body of work, we present potential future research directions on studies related toTrichodermaspp. and their secondary metabolites in agroecosystems. PMID- 26906098 TI - Isolation and characterization of extremely halophilic CO-oxidizing Euryarchaeota from hypersaline cinders, sediments and soils and description of a novel CO oxidizer, Haloferax namakaokahaiae Mke2.3T, sp. nov. AB - The phylogenetic affiliations of organisms responsible for aerobic CO oxidation in hypersaline soils and sediments were assessed using media containing 3.8 M NaCl. CO-oxidizing strains of the euryarchaeotes, Haloarcula, Halorubrum, Haloterrigena and Natronorubrum, were isolated from the Bonneville Salt Flats (UT) and Atacama Desert salterns (Chile). A halophilic euryarchaeote, Haloferax strain Mke2.3(T), was isolated from Hawai'i Island saline cinders. Haloferax strain Mke2.3(T) was most closely related to Haloferax larsenii JCM 13917(T) (97.0% 16S rRNA sequence identity). It grew with a limited range of substrates, and oxidized CO at a headspace concentration of 0.1%. However, it did not grow with CO as a sole carbon and energy source. Its ability to oxidize CO, its polar lipid composition, substrate utilization and numerous other traits distinguished it from H. larsenii JCM 13917(T), and supported designation of the novel isolate as Haloferax namakaokahaiae Mke2.3(T), sp. nov (= DSM 29988, = LMG 29162). CO oxidation was also documented for 'Natronorubrum thiooxidans' HG1 (Sorokin, Tourova and Muyzer 2005), N. bangense (Xu, Zhou and Tian 1999) and N. sulfidifaciens AD2(T) (Cui et al. 2007). Collectively, these results established a previously unsuspected capacity for extremely halophilic aerobic CO oxidation, and indicated that the trait might be widespread among the Halobacteriaceae, and occur in a wide range of hypersaline habitats. PMID- 26906099 TI - Diversity and dispersal capacities of a terrestrial algal genus Klebsormidium (Streptophyta) in polar regions. AB - The distribution of microbial eukaryotes (protists) has been frequently discussed during the last two decades. The ubiquity hypothesis assumes the lack of latitudinal gradients in protist diversity due to their unlimited global dispersal. In this study, we examined the diversity and distribution of the very common, globally distributed green algal genus Klebsormidium across climatic zones, focusing on the polar regions. We tested whether (i) there is comparable diversity among the polar and temperate regions, and (ii) whether a spatial genetic differentiation occurs at the global scale. We collected a total of 58 Arctic, Antarctic and temperate strains, and genetically characterized them by sequencing the rbcL gene and two highly variable chloroplast markers. Our analyses revealed the presence of two different distribution patterns which are supposed to characterize both macroorganisms and protists. On the one hand, we demonstrated unlimited dispersal and intensive gene flow within one of the inferred lineages (superclade B). On the other hand, the majority of Klebsormidium clades showed rather a limited distribution. In addition, we detected a significant decrease of species richness towards the poles i.e. the macroecological pattern typical for macroorganisms. Species within a single protist genus may thus exhibit highly contrasting distribution patterns, based on their dispersal capabilities, which are usually shaped by both intrinsic and extrinsic factors. PMID- 26906100 TI - Mathematical modelling of antimicrobial resistance in agricultural waste highlights importance of gene transfer rate. AB - Antimicrobial resistance is of global concern. Most antimicrobial use is in agriculture; manures and slurry are especially important because they contain a mix of bacteria, including potential pathogens, antimicrobial resistance genes and antimicrobials. In many countries, manures and slurry are stored, especially over winter, before spreading onto fields as organic fertilizer. Thus, these are a potential location for gene exchange and selection for resistance. We develop and analyse a mathematical model to quantify the spread of antimicrobial resistance in stored agricultural waste. We use parameters from a slurry tank on a UK dairy farm as an exemplar. We show that the spread of resistance depends in a subtle way on the rates of gene transfer and antibiotic inflow. If the gene transfer rate is high, then its reduction controls resistance, while cutting antibiotic inflow has little impact. If the gene transfer rate is low, then reducing antibiotic inflow controls resistance. Reducing length of storage can also control spread of resistance. Bacterial growth rate, fitness costs of carrying antimicrobial resistance and proportion of resistant bacteria in animal faeces have little impact on spread of resistance. Therefore, effective treatment strategies depend critically on knowledge of gene transfer rates. PMID- 26906101 TI - Overall condition improvement in a rat model of nephrotic syndrome treated with CellCept nanoliposomes. AB - Purpose To investigate the effect of CellCept nanoliposomes on Adriamycin-induced nephrotic syndrome in rats. Methods To model nephrotic syndrome, rats were injected with 6.5 mg/kg of Adriamycin in the tail vein. The rats were randomly divided into three groups, including a control group, a free mycophenolate mofetil (MMF)-treated group, and a liposome-encapsulated MMF-treated group. Five weeks after the Adriamycin treatment, the free MMF-treated group received CellCept while the liposome-encapsulated MMF-treated group received the CellCept nanoliposomes for 2 weeks. The general condition of the animals was observed, which included urine volume over 24 h, urine protein levels, and serum biochemical indexes. Renal morphology was also observed. Results The level of urine protein over 24 h was increased in the control group, while plasma albumin (ALB) was decreased. The total cholesterol (TC) and triacylglycerol (TG) levels increased significantly (P < 0.05, P < 0.01). The pathological examination of the kidneys showed some abnormalities. In contrast, these parameters were improved significantly in the free mycophenolate mofetil (MMF)-treated and liposome contained mycophenolate mofetil (MMF)-treated groups. Conclusion The CellCept nanoliposomes have a good therapeutic effect on Adriamycin-induced nephrotic syndrome in rats. PMID- 26906102 TI - Sporadic lower motor neuron disease with snake eyes by MRI should be classified as a new entity of lower motor neuron disease with a relatively benign prognosis. PMID- 26906103 TI - Diet quality of Italian yogurt consumers: an application of the probability of adequate nutrient intake score (PANDiet). AB - The diet quality in yogurt consumers and non-consumers was evaluated by applying the probability of adequate nutrient intake (PANDiet) index to a sample of adults and elderly from the Italian food consumption survey INRAN SCAI 2005-06. Overall, yogurt consumers had a significantly higher mean intake of energy, calcium and percentage of energy from total sugars whereas the mean percentage of energy from total fat, saturated fatty acid and total carbohydrate were significantly (p < 0.01) lower than in non-consumers. The PANDiet index was significantly higher in yogurt consumers than in non-consumers, (60.58 +/- 0.33 vs. 58.58 +/- 0.19, p < 0.001). The adequacy sub-score for 17 nutrients for which usual intake should be above the reference value was significantly higher among yogurt consumers. The items of calcium, potassium and riboflavin showed the major percentage variation between consumers and non-consumers. Yogurt consumers were more likely to have adequate intakes of vitamins and minerals, and a higher quality score of the diet. PMID- 26906104 TI - Recent advances in design, synthesis and bioactivity of paclitaxel-mimics. AB - Taxane-type anticancer drugs, including paclitaxel and its semi-synthetic derivatives docetaxel and cabazitaxel, are widely applied to chemotherapy of malignancy like breast cancer, ovarian cancer, non-small cell lung cancer and prostate cancer. However, their clinical applications are generally limited by scarce natural resources, various side effects and multidrug resistance. Therefore, it is significant to develop paclitaxel-mimics with simplified structure, fewer side effects and improved pharmaceutical properties. Based on our investigation on chemistry of paclitaxel, the current review summarized the most recent advances in the design, synthesis and biological activities of paclitaxel-mimics, which could be appealing to researchers in the field of medicinal chemistry and oncology. Meanwhile, smart design, interesting synthesis and potential bioactivities of these novel compounds may also provide valuable reference for the wider scientific communities. PMID- 26906105 TI - Is there a role for urinary podocyte excretion assessment in lupus nephritis? AB - OBJECTIVE: To establish the occurrence and intensity of podocyturia and its relation to grade of disease activity, as defined by clinical and laboratory criteria. METHODS: Prospective, cross-sectional study involving 50 patients with lupus nephritis and 29 controls, which had podocyturia levels determined from random urine samples using an immunofluorescence technique. Disease activity was graded by BILAG (renal criteria) and an additional system used in the service (S2). RESULTS: Fifty patients with lupus nephritis (WHO classes III, IV and V), with a median age of 37 years, were evaluated. Of these, 86.5% were female, and 52% were BILAG A. Podocyturia quantification in the lupus nephritis and control groups differed significantly (p = 0.009). This score was higher in relation to classes III, IV and V. The correlation with C3 consumption was stronger (p = 0.011) than with C4. The highest levels were found in the most active groups (A and B of BILAG and S2). Lower podocyturia correlated with a lower dose of prednisone. There was no association with the intensity of proteinuria, hematuria or pyuria, serum creatinine levels, among others. CONCLUSIONS: Podocyturia assessment, which was performed by immunofluorescence in this study, can be used as an indicator of disease activity with the advantage of being a urinary biomarker. The levels proved to be higher in patients with lupus nephritis than in the controls and were particularly higher in class IV. PMID- 26906106 TI - Role of Rituximab and Rituximab Biosimilars in Diffuse Large B-Cell Lymphoma. AB - Diffuse large B-cell lymphoma (DLBCL), an aggressive non-Hodgkin lymphoma (NHL), is the most-common subtype of NHL. DLBCL can be classified into at least 3 major immunologically distinct types, which contributes to considerable variation in disease prognosis and response to treatment. DLBCL potentially is curable, even when diagnosed at advanced stages. The current standard of care for most patients with untreated or relapsed/refractory DLBCL is chemoimmunotherapy containing rituximab, an anti-CD20 monoclonal antibody. With advanced understanding of the molecular mechanisms involved in the pathogenesis of DLBCL and specific signaling pathways that are activated in different subtypes, potential new therapeutic targets have been identified, some of which are at the late stages of clinical development. This review summarizes the critical role of rituximab in the current standard of care treatment for DLBCL and discusses why rituximab is likely to remain an important component of treatment options for DLBCL in the foreseeable future. In addition, current and emerging therapeutic agents, including potential benefits of rituximab biosimilars, for patients with DLBCL are discussed. The advent of rituximab biosimilars may facilitate accessibility of rituximab-based chemotherapies to patients with DLBCL and has potential cost-saving benefits for healthcare systems globally. PMID- 26906109 TI - Competitive interactions between glucose and lactose with BSA: which sugar is better for children? AB - The interactions of the sugars glucose and lactose with the transport protein bovine serum albumin (BSA) were investigated using fluorescence, FT-IR and circular dichroism (CD) techniques. The results indicated that glucose could be bonded and transported by BSA, mainly involving hydrogen bonds and van der Waals interactions (DeltaH = -86.13 kJ mol(-1)). The obtained fluorescence data from the binding of sugar and BSA were processed by the multivariate curve resolution alternating least squares (MCR-ALS) method, and the extracted concentration profiles showed that the equilibrium constant, rglucose:BSA, was about 7. However, the binding of lactose to BSA did not quench the fluorescence significantly, and this indicated that lactose could not be directly transported by BSA. The binding experiments were further performed using the fluorescence titration method in the presence of calcium and BSA. Calcium was added so that the calcium/BSA reactions could be studied in the presence or absence of glucose, lactose or hydrolysis products. The results showed that hydrolyzed lactose seemed to enhance calcium absorption in bovine animals. It would also appear that for children, lactose provides better nutrition; however, glucose is better for adults. PMID- 26906110 TI - Reproducibility and differentiation of cervical arteriopathies using in vivo high resolution black-blood MRI at 3 T. AB - INTRODUCTION: The aims of the present study are to evaluate the potential of high resolution black-blood MRI (hr-bb-cMRI) to differentiate common cervical arteriopathies and to evaluate interobserver reproducibility. METHODS: Forty three consecutive patients with distinct cervical arteriopathies were examined with cervical hr-bb-cMRI at 3.0 Te with fat-saturated pre- and post-contrast T1w, T2w, and TOF images using dedicated carotid surface coils at our institution. Twenty-three patients had atherosclerotic disease, causing significant stenosis in 12 patients while 11 patients had moderate stenosis. Eight patients presented with cervical vasculitis, and five patients had arterial dissection. Furthermore, seven control subjects with no evidence of carotid disease were included. Two experienced readers blinded to all clinical information reviewed all MR images and classified both carotid and vertebral arteries as affected either by atherosclerosis, dissection, vasculitis, or no disease. Finally, a consensus reading was performed. RESULTS: On a per-vessel level, test performance parameters (sensitivity, specificity, positive predictive value, negative predictive value) were 95, 97.7, 92.9, and 98.5 % for atherosclerotic disease; 91, 100, 100, and 98.7 % for vasculitis; and 100, 100, 100, and 100 % for dissection, respectively. On a per-patient level, performance parameters were 95.7, 85.7, 97.2, and 85.7 % for the diagnosis of atherosclerosis and 100, 100, 100, and 100 % for the diagnosis of dissection and of vasculitis, respectively. Accuracy rates were all above 95 % for all entities. There was a high agreement between observers both in a per-vessel (kappa = 0.83) and in a per-patient analysis (kappa = 0.82). CONCLUSION: This study demonstrates that hr-bb-cMRI is able to non-invasively differentiate between the most common cervical arteriopathies with an excellent interreader reproducibility. PMID- 26906111 TI - The uncinate fasciculus as observed using diffusion spectrum imaging in the human brain. AB - INTRODUCTION: The definitive structure and comprehensive role of the uncinate fasciculus (UF) are still obscure. We aimed to map the human UF white matter tractography and investigate the asymmetry, connectivity, and segmentation of the UF. METHODS: Subcomponents of the UF were analyzed in 9 normal subjects and a 30 subject diffusion spectrum imaging (DSI) template (CMU-30). DSI and microdissection were performed to explore the tractography of the UF. RESULTS: Both methods revealed that it connects the anterior part of the temporal lobe (superior temporal gyrus and temporal pole) with the inferior frontal cortex and the orbitofrontal cortex. The UF starts at the temporal gyrus, runs inferiorly to the inferior frontal occipital fasciculus and splits into two branches, terminating in the ventrolateral frontal cortex and the rostral middle frontal cortex. Our study showed that the cortical areas of termination in the frontal lobe of the UF are the pars triangularis and pars orbitalis. The relative volume of the UF in both hemispheres was calculated. An independent t test was used to determine variances in the value of tract volume between the left and right hemispheres. The volume and the length showed a significant statistical difference in the total volume of the UF. We suggest the UF is leftward asymmetry. CONCLUSIONS: The two parts of the UF were divided, but the conclusion is not consistent with the previous published articles which have shown that the UF is segmented into three parts. Our research facilitates a better understanding of the UF. PMID- 26906113 TI - Direct observation of isolated Damon-Eshbach and backward volume spin-wave packets in ferromagnetic microstripes. AB - The analysis of isolated spin-wave packets is crucial for the understanding of magnetic transport phenomena and is particularly interesting for applications in spintronic and magnonic devices, where isolated spin-wave packets implement an information processing scheme with negligible residual heat loss. We have captured microscale magnetization dynamics of single spin-wave packets in metallic ferromagnets in space and time. Using an optically driven high-current picosecond pulse source in combination with time-resolved scanning Kerr microscopy probed by femtosecond laser pulses, we demonstrate phase-sensitive real-space observation of spin-wave packets in confined permalloy (Ni80Fe20) microstripes. Impulsive excitation permits extraction of the dynamical parameters, i.e. phase- and group velocities, frequencies and wave vectors. In addition to well-established Damon-Eshbach modes our study reveals waves with counterpropagating group- and phase-velocities. Such unusual spin-wave motion is expected for backward volume modes where the phase fronts approach the excitation volume rather than emerging out of it due to the negative slope of the dispersion relation. These modes are difficult to excite and observe directly but feature analogies to negative refractive index materials, thus enabling model studies of wave propagation inside metamaterials. PMID- 26906112 TI - Radiological signs of the syndrome of the trephined. AB - INTRODUCTION: Syndrome of the trephined (ST) is a post-craniectomy complication. It is characterized by the appearance of new neurological symptoms following the craniectomy, which are relieved after cranioplasty. The purpose of our work was to identify radiological signs and imaging biomarkers of the ST. METHODS: CT images of 32 patients were retrospectively analyzed (ST = 13, controls = 19). While the shapes of craniectomy flap were qualitatively assessed, deviation of the midline structures, relative intracranial cerebrospinal fluid (CSF) volume, and the 3rd ventricle's volume were quantitatively measured. RESULTS: We did not find between-group differences in the mean age or number of post-craniectomy days. ST was diagnosed during the second post-craniectomy month. The occurrence of a sunken skin flap sign was similar in both groups (69.23 % in ST group, 57.89 % in control group). Occurrence of paradoxical herniation and deviation of the midline structures were not significantly different between groups. Mean relative intracranial CSF volume was significantly smaller in ST patients (ST = 5.59 %, controls = 8.12 %, p = 0.01). ST patients, compared to controls, had also significantly smaller mean 3rd ventricle volumes (ST = 1748 mm(3), controls = 2772.97 mm(3), p = 0.03). CONCLUSIONS: ST is an infrequent and delayed post craniectomy complication. The most common radiological findings (paradoxical herniation, deviation of the midline structures, and sunken skin flap sign) might not be specific for ST. Significantly lower 3rd ventricle, and relative intracranial CSF volumes, suggest that altered biophysical CSF properties underlie ST pathophysiology. Therefore, volume measurements of 3rd ventricle could be useful for identification of patients who have higher probability of developing the ST. PMID- 26906114 TI - Percutaneous irreversible electroporation for treatment of locally advanced pancreatic cancer following chemotherapy or radiochemotherapy. AB - BACKGROUND: Irreversible electroporation (IRE) is a non-thermal based tumor ablation method used close to vessels and ducts and has the potential of treating locally advanced pancreatic cancer (LAPC). The aim of this study was to evaluate the efficacy and safety of IRE in patients with LAPC after chemo- and/or radio chemotherapy. METHOD: Twenty-four patients with biopsy proven LAPC and who had received chemo- and/or radio-chemotherapy with no signs of metastases were included and treated with ultrasound guided percutaneous IRE under general anesthesia. RESULTS: The median overall survival from diagnosis of LAPC was 17.9 months; this included 7.0 months after IRE. Median time from IRE was 6.1 months to local progression and 2.7 months to observation of metastases. Local control was observed in nine patients. IRE related complications were observed in 11 patients, three of which were serious complications. There was no IRE related mortality. CONCLUSION: Percutaneous IRE is reasonably safe in LAPC after chemo /radio-chemotherapy and with promising results regarding efficacy. PMID- 26906115 TI - ATP binding cassette G transporters and plant male reproduction. AB - The function of ATP Binding Cassette G (ABCG) transporters in the regulation of plant vegetative organs development has been well characterized in various plant species. In contrast, their function in reproductive development particularly male reproductive development received considerably less attention till some ABCG transporters was reported to be associated with anther and pollen wall development in Arabidopsis thaliana and rice (Oryza sativa) during the past decade. This mini-review summarizes current knowledge of ABCG transporters regarding to their roles in male reproduction and underlying genetic and biochemical mechanisms, which makes it evident that ABCG transporters represent one of those conserved and divergent components closely related to male reproduction in plants. This mini-review also discusses the current challenges and future perspectives in this particular field. PMID- 26906117 TI - Characterization of a Thermotolerant Phytase Produced by Rhizopus microsporus var. microsporus Biofilm on an Inert Support Using Sugarcane Bagasse as Carbon Source. AB - The Rhizopus microsporus var. microsporus biofilm was able to produce increased levels of an extracellular thermotolerant phytase using polyethylene and viscose as an inert support in both modified NBRIP medium and modified Khanna medium containing sugarcane bagasse as the carbon source. The enzyme production was strictly regulated by the phosphorus content with optimal production at 0.5 mM of sodium phytate and KH2PO4. The extracellular phytase, RMPhy1, was purified 4.18 fold with 4.78 % recovery using DEAE-cellulose and CM-cellulose. A single protein band with a molecular mass of 35.4 kDa was obtained when the samples were subjected to 10 % SDS-PAGE. The optimum temperature for activity was 55 degrees C and the optimum pH was 4.5. R. microsporus var. microsporus phytase exhibited high stability at 30 and 40 degrees C with a half-life of 115 min at 60 degrees C. The enzyme activity increased in the presence of Ca (2+) and was inhibited by Zn(2+), arsenate, and sodium phosphate. Phytase demonstrated high substrate specificity for sodium phytate with K m = 0.72 mM and V max = 94.55 U/mg of protein and for p-NPP with K m = 0.04 mM and V max = 106.38 U/mg of protein. The enzyme also hydrolyzed ATP, AMPc, glucose 6-phosphate, glucose 1-phosphate, and UDPG. This is the first report on phytase characterization delivered with biofilm technology. The properties of the enzyme account for its high potential for use in biotechnology and the possibility of application in different industrial sectors as feed in the future. PMID- 26906118 TI - Functional Analysis of CP2-Like Domain and SAM-Like Domain in TFCP2L1, Novel Pluripotency Factor of Embryonic Stem Cells. AB - TFCP2L1 is a transcription factor that facilitates establishment and maintenance of pluripotency in embryonic stem cells by forming a complex transcriptional network with other transcription factors (OCT4, SOX2, and NANOG). TFCP2L1 contains two distinct domains, the CP2-like domain at the N-terminus and the SAM like domain at the C-terminus. In this study, we found that TFCP2L1 is hexamerized in solution via the C-terminal SAM-like domain. We also found that homo-oligomerization of SAM-like domain is dependent on the concentration of the proteins. Finally, we found that TFCP2L1 binds directly to DNA via the N-terminal CP2-like domain. PMID- 26906119 TI - Semi-pilot Scale Microbial Oil Production by Trichosporon cutaneum Using Medium Containing Corncob Acid Hydrolysate. AB - In this study, semi-pilot scale microbial oil production by Trichosporon cutaneum using medium containing corncob acid hydrolysate was carried out in a 50-L fermentor. Scale up showed no negative influence on lipid fermentation that no obvious lag phase was observed. Both glucose and xylose could be utilized simultaneously by T. cutaneum, but the utilization rate of xylose was much slower than that of glucose. After 7.6 days of fermentation, the biomass, lipid content, and lipid yield were 21.8 g/L, 53.7 %, and 11.7 g/L, respectively. Also, a high lipid coefficient (lipid yield on sugars consumption) of 26.3 was obtained. Besides microbial oil, polysaccharide was another main product of lipid fermentation that the remaining biomass residue full of polysaccharides after lipid extraction could be one important by-product in future. Overall, this study showed the great potential of industrialization for lipid production by T. cutaneum on low-cost substrates especially for lignocellulosic hydrolysates. PMID- 26906116 TI - Heme Oxygenase-1 in Kidney Health and Disease. AB - SIGNIFICANCE: Acute kidney injury (AKI) and chronic kidney disease (CKD) represent a considerable burden in healthcare. The heme oxygenase (HO) system plays an important role in regulating oxidative stress and is protective in a variety of human and animal models of kidney disease. Preclinical studies of the HO system have led to the development of several clinical trials targeting the enzyme or its products. RECENT ADVANCES: Connection of HO, ferritin, and other proteins involved in iron regulation has provided important insight into mechanisms of damage in AKI. Also, HO-1 expression is important in the pathogenesis of hypertension, diabetic kidney disease, and progression to end stage renal disease. CRITICAL ISSUES: Despite intriguing discoveries, no drugs targeting the HO system have been translated to the clinic. Meanwhile, treatments for AKI and CKD are urgently needed. Many factors have likely contributed to challenges in clinical translation, including variation in animal models, difficulties in obtaining human tissue, and complexity of the disease processes being studied. FUTURE DIRECTIONS: The HO system represents a promising avenue of investigation that may lead to targeted therapeutics. Tissue-specific gene modulation, widening the scope of animal studies, and continued clinical research will provide valuable insight into the role HO plays in kidney homeostasis and disease. Antioxid. Redox Signal. 25, 165-183. PMID- 26906120 TI - In vivo anti-inflammatory activities of the essential oil from Radix Angelicae dahuricae. AB - Although Radix Angelicae dahuricae (Angelica) has been traditionally used in patients with rheumatism arthralgia, its bioactive ingredients remain to be determined. In this study, the essential oil extract of Radix Angelicae dahuricae (EOAD) was assessed for its anti-inflammatory activities against xylene-induced acute ear swelling and carrageenan-induced acute paw edema in mice as well as its anti-inflammatory and immunomodulating properties in Freund's complete adjuvant (FCA)-induced arthritis in rats. We found that EOAD at 100 mg/kg significantly alleviated xylene-induced ear swelling and carrageenan-induced paw edema in mice. Moreover, in the FCA-induced rat arthritis model, EOAD significantly improved hind paw swelling, lowered the adjuvant arthritis score, mitigated synovial hyperplasia, inflammatory cell infiltration, and cartilage destruction in the ankle joint, and reduced the serum levels of inflammatory mediators such as nitric oxide, tumor necrosis factor-alpha, and prostaglandin E2 as well as serum nitric oxide synthase activity. These findings support the fact that the essential oil extract of Angelica contains important active constituents responsible for its anti-inflammatory activities and therefore help to understand the phytotherapeutic effects of Angelica in the treatment of aseptic inflammation. PMID- 26906121 TI - Mucormycosis in Iran: a systematic review. AB - Fungi in the order Mucorales cause acute, invasive and frequently fatal infections in susceptible patients. This study aimed to perform a systematic review of all reported mucormycosis cases during the last 25 years in Iran. After a comprehensive literature search, we identified 98 cases in Iran from 1990-2015. The mean patient age was 39.8 +/- 19.2 years. Diabetes was the most common underlying condition (47.9%), and 22.4% of the patients underwent solid organ or bone marrow transplantation. The most common clinical forms of mucormycosis were rhinocerebral (48.9%), pulmonary (9.2%) and cutaneous (9.2%). Eight cases of disseminated disease were identified. Overall mortality in the identified cases was 40.8%, with the highest mortality rate in patients diagnosed with disseminated infection (75%). The mortality rate in rhinocerebral infection patients was significantly lower (45.8%). Rhinocerebral infection was the most common clinical manifestation in diabetes patients (72.9%). Patients were diagnosed using various methods including histopathology (85.7%), microscopy (12.3%) and culture (2.0%). Rhizopus species were the most prevalent (51.7%), followed by Mucor species (17.2%). Sixty-nine patients were treated with a combination of surgery and antifungal therapy (resulting survival rate, 66.7%). Owing to the high mortality rate of advanced mucormycosis, early diagnosis and treatment may significantly improve survival rates. Therefore, increased monitoring and awareness of this life-threatening disease is critical. PMID- 26906122 TI - Curcumin Induces Apoptosis of Colorectal Cancer Stem Cells by Coupling with CD44 Marker. AB - This study investigated the effect of curcumin on colorectal cancer stem cells (CCSCs) and its possible mechanism. Comparison of the metabolic profiles of human adenomatous polyp (N = 61) and colorectal cancer (CRC) (N = 57) tissue found statistically significant differences (p < 0.05) in their composition of adenosine monophosphate (AMP), adenine, 5'-methythioadenosine, 3-hydroxybutyric acid, prostaglandin E2, threonine, and glutamine. Our cell culture model study found that curcumin treatment (50 MUM for 48 h) did indeed increase apoptosis of CRC cells as well as of CCSCs, but at a significant level only in CD44(+) cells. Further metabolic profile studies of the CRC, CD44(+), and CD44(-) cells indicated that curcumin treatment increased glyceraldehyde and hydroxypropionic acid in CD44(-) cells but decreased glutamine content in both curcumin-treated CRC and CD44(+) cells. Based on our comparison of the metabolic profiles of human tissues and cancer cells, we suggest that curcumin might couple with CD44 and that curcumin-CD44(+) coupling at the cell membrane might have some blocking effect on the transport of glutamine into the cells, thus decreasing the glutamine content in the CD44(+) cells and inducing apoptosis. PMID- 26906123 TI - Innovation, Creation, Inspiration. PMID- 26906124 TI - Cushing's Syndrome From Pituitary Microadenoma and Pulmonary Nodules. AB - Cushing's syndrome is a state of cortisol excess, possibly from a tumor in the pituitary gland, the adrenal gland, or an ectopic nonpituitary ACTH-secreting source. The first form, pituitary in origin, was originally described by Harvey Cushing, MD, and was labeled as Cushing's disease. Long-term therapy with glucocorticoids also can lead to iatrogenic Cushing's syndrome. PMID- 26906125 TI - The Research Doctorate in Nursing: The PhD. AB - When nurses are considering an advanced degree beyond the master's level of educational preparation, a number of considerations may direct the decision making process. The doctorate of philosophy (PhD) in nursing is a research degree that will well serve nurses who have the desire to apply theory and develop formal programs of research, become faculty of nursing, combine clinical practice with formal research, and advance through professional leadership in the ranks of hospitals and health systems organizations. ?. PMID- 26906126 TI - Precision Medicine and the Changing Landscape of Research Ethics. AB - President Barack Obama announced the launch of the National Institutes of Health Precision Medicine Initiative(r) (PMI) in January 2015. Precision medicine includes the concept of individualized or personalized medicine at a more exact level through advances in science and technology, such as genetics and genomics sequencing. Although many disease processes will be investigated through the precision medicine lens for greater understanding and improved treatment responses, oncology research and translation to practice is leading the initiative's debut, referred to as the near-term focus. PMID- 26906127 TI - Cognitive and Situational Precipitants of Loneliness Among Patients With Cancer: A Qualitative Analysis. AB - PURPOSE/OBJECTIVES: To identify situations and thoughts that may precipitate or protect against loneliness experienced by patients with cancer. ? RESEARCH APPROACH: Qualitative. ? SETTING: The hematology/oncology clinic at the Indiana University Melvin and Bren Simon Cancer Center, an outpatient oncology center in Indianapolis. ? PARTICIPANTS: Purposive sample of 15 patients undergoing treatment for multiple myeloma or non-Hodgkin lymphoma. ? METHODOLOGIC APPROACH: Individual, semistructured qualitative interviews were conducted. Theoretical thematic analysis was used to analyze interview data.? FINDINGS: Factors that appeared to precipitate loneliness included several situations (e.g., physical isolation, social constraints such as criticism) and thoughts (e.g., unmet expectations for visits or questions about health, belief that others do not understand their cancer experience). Several situations (e.g., social support, normal routine) and thoughts (e.g., beliefs that time alone is desirable and that others' discomfort with cancer-related discussions is normative) appeared to protect against loneliness. Certain social situations were loneliness-inducing for some patients and not for others, suggesting that patients' thoughts about their situations, rather than the situations themselves, have the greatest impact on their loneliness. ? CONCLUSIONS: The current study fills gaps in loneliness theory by identifying cancer-related situations and thoughts that patients associate with their loneliness. Consistent with theory, patients reported feeling lonely when they had negative thoughts about their social situations. ? INTERPRETATION: Findings inform nursing assessment and intervention strategies to incorporate into care plans. For instance, when conducting assessments, nurses should be more attentive to patients' satisfaction with their social environment than actual characteristics of the environment. Normalizing patients' experiences and encouraging positive thoughts about others' behavior may reduce patients' loneliness. PMID- 26906128 TI - Assessment of Cognitive Impairment and Complaints in Individuals With Colorectal Cancer. AB - PURPOSE/OBJECTIVES: To assess cognitive function in individuals with colorectal cancer (CRC) and identify factors associated with cognitive effects.? DESIGN: Cross-sectional, comparative design.?. SETTING: Midwest hospital.?. SAMPLE: Men and women with (n = 50) and without (n = 50) CRC. ? METHODS: Comparative and regression analyses were performed to assess the relationship between cognition and CRC.? MAIN RESEARCH VARIABLES: Attention, cognitive control, and memory function were assessed with neuropsychological tests and self-report.?. FINDINGS: Compared to healthy volunteers, individuals with CRC performed worse and reported more problems on tasks requiring attention and cognitive control (p < 0.05). After controlling for covariates, poorer performance on tasks of attention and cognitive control was associated (p < 0.001) with having CRC, older age, and less education. In contrast, poorer perceived attention and cognitive control were associated (p < 0.001) with greater fatigue but not CRC. ? CONCLUSIONS: Individuals with CRC are vulnerable to cognitive problems. In addition, older age, less education, and fatigue can increase risk for worse cognitive performance and self-reported cognition.? IMPLICATIONS FOR NURSING: Cognitive problems can profoundly affect an individual's ability to function in everyday life and cope with cancer. Nurses should assess for cognitive problems in patients with CRC and intervene to reduce distress. PMID- 26906129 TI - Beliefs in Chemotherapy and Knowledge of Cancer and Treatment Among African American Women With Newly Diagnosed Breast Cancer. AB - PURPOSE/OBJECTIVES: To examine beliefs regarding the necessity of chemotherapy and knowledge of breast cancer and its treatment in African American women with newly diagnosed breast cancer, and to explore factors associated with women's beliefs and knowledge.?. DESIGN: Descriptive, cross-sectional study.?. SETTING: Six urban cancer centers in Western Pennsylvania and Eastern Ohio.?. SAMPLE: 101 African American women with newly diagnosed breast cancer. ?. METHODS: Secondary analysis using baseline data collected from participants in a randomized, controlled trial at their first medical oncology visit before the first cycle of chemotherapy.?. MAIN RESEARCH VARIABLES: Belief in chemotherapy, knowledge of cancer and recommended treatment, self-efficacy, healthcare system distrust, interpersonal processes of care, symptom distress, and quality of life.?. FINDINGS: African American women endorsed the necessity of chemotherapy. Most women did not know their tumor size, hormone receptors, specific therapy, or why chemotherapy was recommended to them. Women who perceived better interpersonal communication with physicians, less self-efficacy, or were less involved in their own treatment decision making held stronger beliefs about the necessity of chemotherapy. Women without financial difficulty or having stronger social functioning had more knowledge of their cancer and recommended chemotherapy. ?. CONCLUSIONS: African American women with newly diagnosed breast cancer generally agreed with the necessity of chemotherapy. Knowledge of breast cancer, treatment, and risk reduction through adjuvant therapy was limited.?. IMPLICATIONS FOR NURSING: Oncology nurses could help advocate for tailored educational programs to support informed decision making regarding chemotherapy acceptance for African American women. PMID- 26906130 TI - Fear of Progression in Outpatients With Chronic Myeloid Leukemia on Oral Tyrosine Kinase Inhibitors. AB - PURPOSE/OBJECTIVES: To assess fear of progression (FoP) in outpatients with chronic myeloid leukemia (CML) on oral tyrosine kinase inhibitors (TKIs).? DESIGN: Prospective and descriptive.? SETTING: A university-based outpatient cancer clinic in Wuerzburg, Germany. ? SAMPLE: 37 outpatients with CML on oral TKIs. ?. METHODS: FoP was assessed with a questionnaire. Clinical data were extracted from the medical charts.?. MAIN RESEARCH VARIABLES: Frequency and contents of FoP.? FINDINGS: Sum scores and levels of FoP in the sample population (N = 37) were as high as in cancer populations with more unfavorable life expectancies. Regarding single items, fear that medication may harm the body was most prevalent, regardless of group affiliation. The actual fear of disease progression was only ranked sixth out of 12 items for the total sample and was ranked second by the second-generation TKI group. ? CONCLUSIONS: In a sample of outpatients with CML, FoP was frequent and most often generated by fears of treatment side effects.? IMPLICATIONS FOR NURSING: Nurses should be vigilant about FoP in this population. Established questionnaires may help to identify and evaluate this frequent source of distress. Specific communication could reveal unmet informational needs and may help to initiate interventions. Additional studies are needed to confirm the numbers in a larger cohort of patients, to examine the prevalence during the course of disease, to search for potential influences on the outcome (i.e., via adherence), and to extract the best interventions. PMID- 26906131 TI - Functional Quality-of-Life Outcomes Reported by Men Treated for Localized Prostate Cancer: A Systematic Literature Review. AB - PROBLEM IDENTIFICATION: To systematically evaluate the literature for functional quality-of-life (QOL) outcomes following treatment for localized prostate cancer. ?. LITERATURE SEARCH: The MEDLINE(r), CINAHL(r), EMBASE, British Nursing Index, PsycINFO(r), and Web of ScienceTM databases were searched using key words and synonyms for localized prostate cancer treatments.?. DATA EVALUATION: Of the 2,191 articles screened for relevance and quality, 24 articles were reviewed. Extracted data were tabulated by treatment type and sorted by dysfunction using a data-driven approach.?. SYNTHESIS: All treatments caused sexual dysfunction and urinary side effects. Radiation therapy caused bowel dysfunction, which could be long-term or resolved within a few years. Sexual function could take years to return. Urinary incontinence resolved within two years of surgery but worsened following radiation therapy. Fatigue was worse during treatment with adjuvant androgen-deprivation therapy, and some men experienced post-treatment fatigue for several years. ?. CONCLUSIONS: This review identified that QOL outcomes reported by men following different treatments for localized prostate cancer are mostly recorded using standardized health-related QOL outcome measures. Such outcome measures collect data about body system functions but limit understanding of men's QOL following treatment for prostate cancer. Holistic outcome measures are needed to capture data about men's QOL for several years following the completion of treatment for localized prostate cancer.?. IMPLICATIONS FOR PRACTICE: Nurses need to work with men to facilitate information sharing, identify supportive care needs, and promote self-efficacy, and they should make referrals to specialist services, as appropriate. PMID- 26906132 TI - Administration and Handling of Talimogene Laherparepvec: An Intralesional Oncolytic Immunotherapy for Melanoma. AB - PURPOSE/OBJECTIVES: To describe the administration and handling requirements of oncolytic viruses in the context of talimogene laherparepvec (ImlygicTM), a first in-class oncolytic immunotherapy.?. DATA SOURCES: Study procedures employed in clinical trials, in particular the OPTiM study.?. DATA SYNTHESIS: Evaluation of nursing considerations for administration of talimogene laherparepvec.?. CONCLUSIONS: Talimogene laherparepvec is administered through a series of intralesional injections into cutaneous, subcutaneous, or nodal tumors (with ultrasound guidance as needed) during an outpatient clinic visit. A single insertion point is recommended; however, multiple insertion points are acceptable if the tumor radius exceeds the needle's radial reach. Talimogene laherparepvec must be evenly distributed throughout the tumor through each insertion site. Talimogene laherparepvec requires storage at -90 degrees C to -70 degrees C and, once thawed, should be administered immediately or stored in its original vial and carton and protected from light in a refrigerator (2 degrees C to 8 degrees C). ?. IMPLICATIONS FOR NURSING: Because talimogene laherparepvec can be administered in the outpatient setting, nurses will be pivotal for appropriate integration and administration of this unique and effective therapy. PMID- 26906133 TI - Nursing Roles in Cardiac Safety: Romidepsin in Patients With T-Cell Lymphoma. AB - PURPOSE/OBJECTIVES: To provide information to help nurses mitigate cardiac risks among patients receiving romidepsin (Istodax(r)), a histone deacetylase (HDAC) inhibitor approved by the U.S. Food and Drug Administration for the treatment of relapsed/refractory cutaneous and peripheral T-cell lymphoma. ?. DATA SOURCES: Clinical studies of romidepsin represented the primary data sources. Supporting references included class information on HDAC inhibitors, as well as data regarding the impact of electrolyte imbalances and antiemetic treatment on electrocardiogram (ECG) data.?. DATA SYNTHESIS: Cardiac concerns during treatment with romidepsin are multifactorial. Electrolyte deficiencies, which are associated with ECG abnormalities and dysrhythmias, are common among patients with T-cell lymphoma. In addition, clinically insignificant changes in the corrected QT interval reported with romidepsin are primarily attributable to concomitant use of prophylactic antiemetics and likely exaggerated by transient increases in heart rate. ?. CONCLUSIONS: Data support the cardiac safety of romidepsin while cautioning about the need for nurses' vigilance regarding consistent electrolyte supplementation, appropriate antiemetic selection, and heart rate monitoring. ?. IMPLICATIONS FOR NURSING: By recognizing drug-related and non-drug-related influences on cardiac safety during treatment with romidepsin, as well as other anticancer agents, nurses can identify risks, report them, and recommend appropriate interventions, which, ultimately, facilitates improved patient outcomes. PMID- 26906134 TI - Ocular Toxicity of Tyrosine Kinase Inhibitors. AB - PURPOSE/OBJECTIVES: To review common tyrosine kinase inhibitors, as well as their ocular side effects and management.?. DATA SOURCES: A comprehensive literature search was conducted using CINAHL(r), PubMed, and Cochrane databases for articles published since 2004 with the following search terms. DATA SYNTHESIS: Tyrosine kinase inhibitors can cause significant eye toxicity.?. CONCLUSIONS: Given the prevalence of new tyrosine kinase inhibitor therapies and the complexity of possible pathogenesis of ocular pathology, oncology nurses can appreciate the occurrence of ocular toxicities and the role of nursing in the management of these problems.?. IMPLICATIONS FOR NURSING: Knowledge of the risk factors and etiology of ocular toxicity of targeted cancer therapies can guide nursing assessment, enhance patient education, and improve care management. Including a review of eye symptoms and vision issues in nursing assessment can enhance early detection and treatment of ocular toxicity. PMID- 26906135 TI - Explicit Assumptions About Knowing. AB - Conceptual Foundations is a new column for Oncology Nursing Forum that focuses on the frameworks that underpin research and practice initiatives. The purpose of this inaugural column is to provide an overview of what conceptual frameworks are, related terms, the role of conceptual frameworks in the research process, and why these frameworks matter. PMID- 26906136 TI - Whole Exome Sequencing: The Next Phase of Genetics Care. AB - Exome sequencing is a technique for sequencing all of the genes that code for functioning proteins in the genome. It is now being used to identify mutations in families with suspected hereditary cancer syndromes where single-gene testing or testing for a panel of genes has not been able to detect a mutation. Oncology nurses need to anticipate that more patients and families will be undergoing this testing and be prepared to explain basic concepts about this new technology. PMID- 26906137 TI - The International Society of Nurses in Cancer Care: Position Statements Can Aid Nurses to Think Globally and Act Locally. AB - The number of new cases of cancer is expected to rise by about 70% during the next two decades, and people living in low- and middle-income countries will experience a disproportionate burden of this increase. Oncology nurses are positioned to take the lead in addressing this looming health crisis. Such efforts will gain momentum and have a greater impact if nurses around the world collaborate. The purpose of this article is to describe the role of the International Society of Nurses in Cancer Care in leading this effort, with a particular focus on three specific position statements that nursing societies and nurse leaders can use to advance cancer prevention and control in their own institution or country.?. PMID- 26906138 TI - Patterns of Response in Parents of Children With Cancer: An Integrative Review. AB - PROBLEM IDENTIFICATION: To identify patterns of response of parents in relation to taking care of their child with cancer.?. LITERATURE SEARCH: The search was performed using CINAHL(r) and Scopus in February 2013.?. DATA EVALUATION: The selection process resulted in 18 articles with a wide range of methodologic approaches. The description of the research methods of each study and the relevance of the results in comparison to the purpose of this review were established as assessment criteria.?. SYNTHESIS: The results of the studies were analyzed using Meleis's Transition Theory, identifying a vast number of patterns of response developed by the parents. These patterns of response were analyzed, compared, and split into four themes.?. CONCLUSIONS: Using this methodology, a wide range of behaviors, attitudes, and competencies associated with the circumstance of parents caring for a child with cancer could be identified. ?. IMPLICATIONS FOR PRACTICE: Knowledge of the patterns of response will enable nurses to lead parents through a healthy transition process in caring for their children with cancer. PMID- 26906139 TI - Effects of Making Art and Listening to Music on Symptoms Related to Blood and Marrow Transplantation. AB - PURPOSE/OBJECTIVES: To understand the benefits of making art and listening to music and whether those activities may be beneficial for reducing symptoms associated with blood and marrow transplantation. ?. DESIGN: A randomized, three group, pre-/post-pilot design.?. SETTING: Outpatient Blood and Marrow Transplant Clinic at the University of Kansas Cancer Center in Kansas City.?. SAMPLE: 39 adults aged from 22-74 years receiving blood and marrow transplantations.?. METHODS: Participants were randomly assigned to one of three groups. MAIN RESEARCH VARIABLES: Therapy-related symptoms, state anxiety, and physiologic distress.?. FINDINGS: Of the 39 participants, 14 were randomized to the control group, 14 to the art group, and 11 to the diversional music group. No significant differences in age, gender, ethnicity, or diagnosis existed between groups. No statistical differences were found between groups on all measures following the intervention. ?. CONCLUSIONS: Although the results of the current study did not indicate significant differences, healthcare professionals may still consider creative therapies as a viable option for patients within hospital or outpatient clinics because they do not require specialty training or costly resources, and they may be an enjoyable activity to occupy time for patients and caregivers.?. IMPLICATIONS FOR NURSING: Art making and music listening are safe and desirable for patients undergoing blood and marrow transplantation in an outpatient clinic. Nurses might consider partnering with therapists to offer these creative therapies as diversion during treatment. PMID- 26906140 TI - Accidental Fall Rates in Community-Dwelling Adults Compared to Cancer Survivors During and Post-Treatment: A Systematic Review With Meta-Analysis. AB - PURPOSE/OBJECTIVES: To identify whether rates of accidental falls are greater for cancer survivors living in the community during or post-treatment than people with no history of cancer.?. DATA SOURCES: In a systematic literature review that was conducted in December 2013, MEDLINE(r), EMBASE, PubMed, and Web of Science were searched for cancer or oncology and accidental falls in prospective and retrospective cohort and case-controlled studies. Studies were included if they were conducted in a community-dwelling adult population and excluded if they were conducted in acute hospitals and hospice.?. DATA SYNTHESIS: Of 484 articles initially identified, 10 were included in the review. Of these, three included a control or comparator group and had comparable outcome measures to include in a meta-analysis. The risk ratio for falls for the group with cancer was 1.11.?. CONCLUSIONS: Accidental fall rates in community-dwelling adults with a cancer diagnosis are greater than rates of falls in adults without cancer; this elevated rate remains after acute care is finished. Patients undergoing active treatment have greater rates of falls. Pain, fatigue, and deconditioning may affect fall rates in the longer term. ?. IMPLICATIONS FOR NURSING: Nurses have the capacity to reduce risk of falls in community-dwelling cancer survivors during or post treatment through provision of information, advocacy, and support around pain and fatigue management and promotion of physical activity. PMID- 26906141 TI - Decay, Transformation, and Growth: Meaning-Making Processes of Patients With Acute Leukemia Within the First Year After Diagnosis or Relapse. AB - PURPOSE/OBJECTIVES: To explore the processes through which patients construct their meanings of acute leukemia (AL).? RESEARCH APPROACH: An exploratory design was employed using serial, in-depth interviews, guided by Smith's Interpretative Phenomenological Analysis approach.? SETTING: Two inpatient hematology clinics in the United Kingdom.? PARTICIPANTS: 10 adult patients with AL. ? METHODOLOGIC APPROACH: Two serial interviews were conducted with each participant, two to four weeks apart, within the first year of diagnosis or post-relapse.? FINDINGS: AL creates a state of imbalance, which may initiate a search for new equilibrium. Patients' journeys toward making sense of their illness may involve three interchangeable processes. CONCLUSIONS: Findings of this contextually and methodologically novel study highlight the complex nature of sense-making for patients experiencing AL.? INTERPRETATION: Nurses can take valuable lessons on how to manage the invisibility of AL, enhance trust in healthcare professionals, address the impact of isolation, and facilitate the making-sense processes of patients in ways that favor their short- and long-term psychosocial adjustment. PMID- 26906142 TI - 2016 Oncology Nursing Society Annual Congress: Podium, E-Poster, and Poster Session Abstracts. AB - Abstracts appear as they were submitted and have not undergone editing or the Oncology Nursing Forum's review process. Only abstracts that will be presented appear online. Poster numbers are subject to change. For updated poster numbers, visit congress.ons.org or check the Congress guide. Data published in abstracts presented at ONS's Annual Congress are embargoed until the conclusion of the presentation. Coverage and/or distribution of an abstract, poster, or any of its supplemental material to or by the news media, any commercial entity, or individuals, including the authors of said abstract, is strictly prohibited until the embargo is lifted. Promotion of general topics and speakers is encouraged within these guidelines. PMID- 26906143 TI - Assessing causes of quality deterioration of groundwater in Puttalam, Sri Lanka, using isotope and hydrochemical tools. AB - Extensive extraction of groundwater has resulted in deterioration of the groundwater quality in the Puttalam area in the northwestern coastal zone of Sri Lanka. This situation led us to carry out the present comprehensive study based on environmental isotopic ((18)O, (2)H, (3)H) and geochemical evaluation to understand the root cause for water quality deterioration. The isotopic data suggest that the surface water and shallow groundwaters are subjected to intensive evaporation and, as a result, increase in their salinity. Deep groundwater of the area is mostly recharged by direct infiltration of rainwater and at few places by nearby surface water bodies. The salinity increase of deep groundwater depends on the specific hydrogeological zones and would be due to dissolution of salts which are precipitated in soil through the seawater spray over the time, dissolution of minerals in geological matrix and leaching of salts from salterns. The quality of the deep groundwater is relatively good in the granitic gneiss zone and nearby areas outside the sedimentary aquifer. There is no evidence from isotope and hydrogeochemical evaluation for seawater intrusion into groundwater in the Puttalam area. PMID- 26906144 TI - Drainage isolation and climate change-driven population expansion shape the genetic structures of Tuber indicum complex in the Hengduan Mountains region. AB - The orogenesis of the Qinghai-Tibetan Plateau and the Quaternary climate changes have played key roles in driving the evolution of flora and fauna in Southwest China, but their effects on higher fungi are poorly addressed. In this study, we investigated the phylogeographic pattern of the Tuber indicum species complex, an economically important fungal group distributed in the Hengduan Mountains region. Our data confirmed the existence of two distinct lineages, T. indicum and T. himalayense, within this species complex. Three geographic groups (Groups W, N and C) were revealed within T. indicum, with Group W found in the paleo-Lancang River region, while Groups N and C corresponded to the two banks along the contemporary Jinsha River, suggesting that rivers have acted as barriers for gene flow among populations from different drainages. Historical range expansion resulted from climate changes was inferred in Group C, contributing to the observed gene flow among geographic populations within this group. Although no significant geographic structure was identified in T. himalayense, evidence of drainage isolation for this species was also detected. Our findings demonstrate that both topographic changes and Quaternary climate oscillations have played important roles in driving the genetic structures of the T. indicum species complex. PMID- 26906145 TI - Electrochemical Methods to Study Photoluminescent Carbon Nanodots: Preparation, Photoluminescence Mechanism and Sensing. AB - With unique and tunable photoluminescence (PL) properties, carbon nanodots (CNDs) as a new class of optical tags have been extensively studied. Because of their merits of controllability and sensitivity to the surface of nanomaterials, electrochemical methods have already been adopted to study the intrinsic electronic structures of CNDs. In this review, we mainly deal with the electrochemical researches of CNDs, including preparation, PL mechanism, and biosensing. PMID- 26906146 TI - Deaths: Leading Causes for 2013. AB - OBJECTIVES: This report presents final 2013 data on the 10 leading causes of death in the United States by age, sex, race, and Hispanic origin. Leading causes of infant, neonatal, and postneonatal death are also presented. This report supplements "Deaths: Final Data for 2013," the National Center for Health Statistics' annual report of final mortality statistics. METHODS: Data in this report are based on information from all death certificates filed in the 50 states and the District of Columbia in 2013. Causes of death classified by the International Classification of Diseases, Tenth Revision (ICD-10) are ranked according to the number of deaths assigned to rankable causes. Cause-of-death statistics are based on the underlying cause of death. RESULTS: In 2013, the 10 leading causes of death were, in rank order: Diseases of heart; Malignant neoplasms; Chronic lower respiratory diseases; Accidents (unintentional injuries); Cerebrovascular diseases; Alzheimer's disease; Diabetes mellitus; Influenza and pneumonia; Nephritis, nephrotic syndrome and nephrosis; and Intentional self-harm (suicide). They accounted for 74% of all deaths occurring in the United States. Differences in the rankings are evident by age, sex, race, and Hispanic origin. Leading causes of infant death for 2013 were, in rank order: Congenital malformations, deformations and chromosomal abnormalities; Disorders related to short gestation and low birth weight, not elsewhere classified; Newborn affected by maternal complications of pregnancy; Sudden infant death syndrome; Accidents (unintentional injuries); Newborn affected by complications of placenta, cord and membranes; Bacterial sepsis of newborn; Respiratory distress of newborn; Diseases of the circulatory system; and Neonatal hemorrhage. Important variations in the leading causes of infant death are noted for the neonatal and postneonatal periods. PMID- 26906147 TI - Pulmonary Rehabilitation Exercise Prescription in Chronic Obstructive Pulmonary Disease: Review of Selected Guidelines: AN OFFICIAL STATEMENT FROM THE AMERICAN ASSOCIATION OF CARDIOVASCULAR AND PULMONARY REHABILITATION. AB - Chronic obstructive pulmonary disease (COPD) is associated with disabling dyspnea, skeletal muscle dysfunction, and significant morbidity and mortality. Current guidelines recommend pulmonary rehabilitation (PR) to improve dyspnea, functional capacity, and quality of life. Translating exercise science into safe and effective exercise training requires interpretation and use of multiple guidelines and recommendations. The purpose of this statement is to summarize for clinicians 3 current chronic obstructive pulmonary disease guidelines for exercise that may be used to develop exercise prescriptions in the PR setting. The 3 guidelines have been published by the American College of Sports Medicine, the American Thoracic Society/European Respiratory Society, and the American Association of Cardiovascular and Pulmonary Rehabilitation. In addition to summarizing these 3 guidelines, this statement describes clinical applications, explores areas of uncertainty, and suggests strategies for providing effective exercise training, given the diversity of guidelines and patient complexity. PMID- 26906148 TI - Long-Term Exercise Training in Patients With Advanced Chronic Heart Failure: SUSTAINED BENEFITS ON LEFT VENTRICULAR PERFORMANCE AND EXERCISE CAPACITY. AB - PURPOSE: In moderately impaired, stable chronic heart failure (CHF) patients, exercise training (ET) enhances exercise capacity. In contrast, the therapeutic benefits of regular ET in patients with advanced CHF, especially in the long term, are limited or conflicting. Therefore, the aim of the present investigation was to elucidate whether ET performed over 12 months would improve left ventricular performance and exercise capacity in patients with advanced CHF. METHODS: Thirty-seven patients with CHF and New York Heart Association (NYHA) class IIIb were randomized to a sedentary lifestyle or daily ET on a cycle ergometer (in-hospital and home-based at 50%-60% of maximal exercise capacity). Cardiopulmonary exercise testing and echocardiography were performed at baseline, 3, 6, and 12 months. RESULTS: Exercise training resulted in continuous decreases in left ventricular end-diastolic diameter at 3, 6, and 12 months versus baseline (all P < .05). This was accompanied by a significant increase in resting left ventricular ejection fraction from 24.1% +/- 1.2% at baseline to 38.4% +/- 2.0% at 12-month followup (P < .05). Moreover, ET patients increased exercise capacity measured by maximal oxygen uptake (Equation is included in full-text article.)O2max at 3, 6, and 12 months compared with baseline: 15.3 +/- 0.8 mL/min/kg, 17.8 +/- 0.8 mL/min/kg, 19.0 +/- 0.7 mL/min/kg, and 19.5 +/- 0.9 mL/min/kg, respectively (all P < .05 vs baseline). This was associated with a reduced NYHA classification. CONCLUSIONS: Exercise training over 12 months resulted in an improvement in exercise capacity and reversing of left ventricular remodeling in patients with advanced CHF (NYHA IIIb). These beneficial adaptations continued to improve up to 6 months and remained stable thereafter. PMID- 26906150 TI - Genotypic variation in response to salinity in a new sexual germplasm of Cenchrus ciliaris L. AB - As part of a breeding program for new salt-tolerant sexual genotypes of Cenchrus ciliaris L., here we evaluated the salt-stress response of two new sexual hybrids, obtained by controlled crosses, at seedling and germination stages. A seedling hydroponic experiment with 300 mM NaCl was performed and physiological variables and growth components were evaluated. While salt-treated sexual material did not show a decrease in productivity with respect to control plants, a differential response in some physiological characteristics was observed. Sexual hybrid 1-9-1 did not suffer oxidative damage and its proline content did not differ from that of control treatment. By contrast, sexual hybrid 1-7-11 suffered oxidative damage and accumulated proline, maintaining its growth under saline stress. At the germination stage, sexual hybrid 1-9-1 presented the highest Germination Rate Index at the maximum NaCl concentration assayed, suggesting an ecological advantage in this genotype. These new sexual resources are promising maternal parental with differential response to salt and could be incorporated in a breeding program of C. ciliaris in the search of new genotypes tolerant to salinity. PMID- 26906151 TI - "Vaginal seeding" of infants born by caesarean section. PMID- 26906152 TI - Ferroelasticity and domain physics in two-dimensional transition metal dichalcogenide monolayers. AB - Monolayers of transition metal dichalcogenides can exist in several structural polymorphs, including 2H, 1T and 1T'. The low-symmetry 1T' phase has three orientation variants, resulting from the three equivalent directions of Peierls distortion in the parental 1T phase. Using first-principles calculations, we predict that mechanical strain can switch the relative thermodynamic stability between the orientation variants of the 1T' phase. We find that such strain induced variant switching only requires a few percent elastic strain, which is eminently achievable experimentally with transition metal dichalcogenide monolayers. Calculations indicate that the transformation barrier associated with such variant switching is small (<0.2 eV per chemical formula unit), suggesting that strain-induced variant switching can happen under laboratory conditions. Monolayers of transition metal dichalcogenides with 1T' structure therefore have the potential to be ferroelastic and shape memory materials with interesting domain physics. PMID- 26906153 TI - [Epstein-Barr virus associated acute retinal necrosis]. AB - CASE REPORT: This article reports a case of an Epstein-Barr virus (EBV) associated acute retinal necrosis. A 72-year-old male patient presented in the emergency department complaining of progressive loss of vision. During patient management an acute retinal necrosis was suspected and the subsequent diagnostics from a vitreal body biopsy showed positive results only for the EBV genome. OBJECTIVE: The EBV is a rare cause of ocular inflammation. With this report we would like to draw the attention of colleagues to this unusual finding. CONCLUSION: Although EBV screening is not part of the standard diagnostic procedure, its implementation in relevant clinical situations could possibly assist the differentiation between causal relationship and morbidity. PMID- 26906154 TI - [Increased prevalence of congenital dacryostenosis following cesarean section]. AB - BACKGROUND: Congenital nasolacrimal duct obstruction (dacryostenosis) with a persisting membrane at Hasner's valve is the most common cause of persistent tear and ocular discharge in infants. PURPOSE: To evaluate whether there is an association between congenital dacryostenosis and delivery via cesarean section. MATERIAL AND METHODS: In a prospective study we examined 107 children (mean age 9.2 +/- 7.1 months) with congenital dacryostenosis. We evaluated data about the mode of delivery (vaginal delivery versus cesarean section) and gestational age at the time of birth. Within the first 8 months of life children were treated by probing using local anesthesia, whereas older children were treated using general anesthesia. After the age of 11 months treatment included nasolacrimal duct intubation with a bicanalicular stent. Statistical analyses were performed using binomial tests, Fisher's exact test and the t-test. RESULTS: In this study 51 children delivered by cesarean section were compared with 56 children delivered by spontaneous vaginal delivery. A total of 44 age-matched pairs from both groups were evaluated in order to eliminate confounding factors due to gestational age at delivery. Based on the published rate of cesarean sections from the same region of the State of Hesse between 2002-2004 we observed a statistically significant association between congenital dacryostenosis and delivery by cesarean section among the 88 age-matched patients (P = 0.009). Moreover, subgroup analysis revealed a significant association between congenital dacryostenosis and delivery by primary cesarean section (P = 0.00004). The prevalence of surgical treatment was not statistically different between both groups based on the mode of delivery (P = 0.8). CONCLUSION: Our results suggest that delivery via cesarean section is associated with a significantly higher prevalence of congenital dacryostenosis. PMID- 26906155 TI - Neuroanatomy and Neurochemistry of Mouse Cornea. AB - PURPOSE: To investigate the entire nerve architecture and content of the two main sensory neuropeptides in mouse cornea to determine if it is a good model with similarities to human corneal innervation. METHODS: Mice aged 1 to 24 weeks were used. The corneas were stained with neuronal-class betaIII-tubulin, calcitonin gene-related peptide (CGRP), and substance P (SP) antibodies; whole-mount images were acquired to build an entire view of corneal innervation. To test the origin of CGRP and SP, trigeminal ganglia (TG) were processed for immunofluorescence. Relative corneal nerve fiber densities or neuron numbers were assessed by computer-assisted analysis. RESULTS: Between 1 and 3 weeks after birth, mouse cornea was mainly composed of a stromal nerve network. At 4 weeks, a whorl-like structure (or vortex) appeared that gradually became more defined. By 8 weeks, anatomy of corneal nerves had reached maturity. Epithelial bundles converged into the central area to form the vortex. The number and pattern of whorl-like structures were different. Subbasal nerve density and nerve terminals were greater in the center than the periphery. Nerve fibers and terminals that were CGRP-positive were more abundant than SP-positive nerves and terminals. In trigeminal ganglia, the number of CGRP-positive neurons significantly outnumbered those positive for SP. CONCLUSIONS: This is the first study to show a complete map of the entire corneal nerves and CGRP and SP sensory neuropeptide distribution in the mouse cornea. This finding shows mouse corneal innervation has many similarities to human cornea and makes the mouse an appropriate model to study pathologies involving corneal nerves. PMID- 26906156 TI - Does the Location of Bruch's Membrane Opening Change Over Time? Longitudinal Analysis Using San Diego Automated Layer Segmentation Algorithm (SALSA). AB - PURPOSE: We determined if the Bruch's membrane opening (BMO) location changes over time in healthy eyes and eyes with progressing glaucoma, and validated an automated segmentation algorithm for identifying the BMO in Cirrus high definition coherence tomography (HD-OCT) images. METHODS: We followed 95 eyes (35 progressing glaucoma and 60 healthy) for an average of 3.7 +/- 1.1 years. A stable group of 50 eyes had repeated tests over a short period. In each B-scan of the stable group, the BMO points were delineated manually and automatically to assess the reproducibility of both segmentation methods. Moreover, the BMO location variation over time was assessed longitudinally on the aligned images in 3D space point by point in x, y, and z directions. RESULTS: Mean visual field mean deviation at baseline of the progressing glaucoma group was -7.7 dB. Mixed effects models revealed small nonsignificant changes in BMO location over time for all directions in healthy eyes (the smallest P value was 0.39) and in the progressing glaucoma eyes (the smallest P value was 0.30). In the stable group, the overall intervisit-intraclass correlation coefficient (ICC) and coefficient of variation (CV) were 98.4% and 2.1%, respectively, for the manual segmentation and 98.1% and 1.9%, respectively, for the automated algorithm. CONCLUSIONS: Bruch's membrane opening location was stable in normal and progressing glaucoma eyes with follow-up between 3 and 4 years indicating that it can be used as reference point in monitoring glaucoma progression. The BMO location estimation with Cirrus HD-OCT using manual and automated segmentation showed excellent reproducibility. PMID- 26906157 TI - Dlg-1 Interacts With and Regulates the Activities of Fibroblast Growth Factor Receptors and EphA2 in the Mouse Lens. AB - PURPOSE: We previously showed that Discs large-1 (Dlg-1) regulates lens fiber cell structure and the fibroblast growth factor receptor (Fgfr) signaling pathway, a pathway required for fiber cell differentiation. Herein, we investigated the mechanism through which Dlg-1 regulates Fgfr signaling. METHODS: Immunofluorescence was used to measure levels of Fgfr1, Fgfr2, and activated Fgfr signaling intermediates, pErk and pAkt, in control and Dlg-1-deficient lenses that were haplodeficient for Fgfr1 or Fgfr2. Immunoblotting was used to measure levels of N-cadherin, EphA2, beta-catenin, and tyrosine-phosphorylated EphA2, Fgfr1, Fgfr2, and Fgfr3 in cytoskeletal-associated and cytosolic fractions of control and Dlg-1-deficient lenses. Complex formation between Dlg-1, N-cadherin, beta-catenin, Fgfr1, Fgfr2, Fgfr3, and EphA2 was assessed by coimmunoprecipitation. RESULTS: Lenses deficient for Dlg-1 and haplodeficient for Fgfr1 or Fgfr2 showed increased levels of Fgfr2 or Fgfr1, respectively. Levels of pErk and pAkt correlated with the level of Fgfr2. N-cadherin was reduced in the cytoskeletal-associated fraction and increased in the cytosolic fraction of Dlg-1 deficient lenses. Dlg-1 complexed with beta-catenin, EphA2, Fgfr1, Fgfr2, and Fgfr3. EphA2 complexed with N-cadherin, beta-catenin, Fgfr1, Fgfr2, and Fgfr3. Levels of these interactions were altered in Dlg-1-deficient lenses. Loss of Dlg 1 led to changes in Fgfr1, Fgfr2, Fgfr3, and EphA2 levels and to greater changes in the levels of their activation. CONCLUSIONS: Dlg-1 complexes with and regulates the activities of EphA2, Fgfr1, Fgfr2, and Fgfr3. As EphA2 contains a Psd95/Dlg/ZO-1 (PDZ) binding motif, whereas Fgfrs do not, we propose that the PDZ protein, Dlg-1, modulates Fgfr signaling through regulation of EphA2. PMID- 26906158 TI - Down-regulation of 14-3-3 Zeta Inhibits TGF-beta1-Induced Actomyosin Contraction in Human Trabecular Meshwork Cells Through RhoA Signaling Pathway. AB - PURPOSE: The aim of this study was to describe the expression and distribution of 14-3-3 zeta in trabecular meshwork (TM) cells and its regulatory role in the actomyosin system. METHODS: The expression of 14-3-3 zeta was detected using Western blot analysis, RT-PCR, and immunofluorescence staining. TGF-beta1 was used to induce cell contraction. Changes in the levels of 14-3-3 zeta, total RhoA, and the phosphorylation of myosin light chain (MLC) and cofilin were determined using Western blot analysis. The effects of 14-3-3 zeta knockdown on the actin cytoskeleton and focal adhesion were determined using immunofluorescence. The mRNA levels of fibronectin and collagen I and III were examined using quantitative RT-PCR. The contraction of TM cells was detected using collagen gel contraction (CGC) assays. The activation of the RhoA pathway was analyzed using a specific kit. RESULTS: The 14-3-3 zeta protein was highly expressed in TM cells. Down-regulation of 14-3-3 zeta resulted in the following: a decrease in the phosphorylation of both MLC and cofilin, a decrease in the formation of stress fibers and focal adhesion, alteration of the mRNA composition of the extracellular matrix (ECM), and the inhibition of TGF-beta1-induced cell contraction. In addition, silencing of 14-3-3 zeta directly decreased total RhoA levels in TM cells. CONCLUSIONS: Collectively, our data suggest that 14-3-3 zeta plays a crucial role in regulating cytoskeletal structures, ECM homeostasis, and TGF-beta1-induced contraction in TM cells by acting through the RhoA signaling pathway. PMID- 26906159 TI - Human Vision-Motivated Algorithm Allows Consistent Retinal Vessel Classification Based on Local Color Contrast for Advancing General Diagnostic Exams. AB - PURPOSE: Abnormalities of blood vessel anatomy, morphology, and ratio can serve as important diagnostic markers for retinal diseases such as AMD or diabetic retinopathy. Large cohort studies demand automated and quantitative image analysis of vascular abnormalities. Therefore, we developed an analytical software tool to enable automated standardized classification of blood vessels supporting clinical reading. METHODS: A dataset of 61 images was collected from a total of 33 women and 8 men with a median age of 38 years. The pupils were not dilated, and images were taken after dark adaption. In contrast to current methods in which classification is based on vessel profile intensity averages, and similar to human vision, local color contrast was chosen as a discriminator to allow artery vein discrimination and arterial-venous ratio (AVR) calculation without vessel tracking. RESULTS: With 83% +/- 1 standard error of the mean for our dataset, we achieved best classification for weighted lightness information from a combination of the red, green, and blue channels. Tested on an independent dataset, our method reached 89% correct classification, which, when benchmarked against conventional ophthalmologic classification, shows significantly improved classification scores. CONCLUSIONS: Our study demonstrates that vessel classification based on local color contrast can cope with inter- or intraimage lightness variability and allows consistent AVR calculation. We offer an open source implementation of this method upon request, which can be integrated into existing tool sets and applied to general diagnostic exams. PMID- 26906160 TI - The Association Between Subretinal Drusenoid Deposits in Older Adults in Normal Macular Health and Incident Age-Related Macular Degeneration. AB - PURPOSE: Subretinal drusenoid deposits (SDD) have been associated with the progression to late age-related macular degeneration (AMD). To determine whether SDD in eyes in normal macular health increases risk for early AMD, this study examined the association between presence of SDD at baseline in a cohort of older adults in normal macular health and incident AMD 3 years later. METHODS: Subjects enrolled in the Alabama Study on Early Age-Related Macular Degeneration (ALSTAR) were assessed for the presence of SDD using color fundus photos, infrared reflectance and fundus autofluorescence images, and spectral-domain optical coherence tomography volumes. The study sample included 799 eyes from 455 participants in normal macular health per grading of color fundus photographs using the 9-step Age-Related Eye Disease Study (AREDS) classification system. Age related macular degeneration was defined as eyes having an AREDS grade >=2 at the 3-year follow-up. RESULTS: Twenty-five percent of participants had SDD in one or both eyes at baseline. At follow-up visit, 11.9% of eyes in the sample developed AMD. Compared to eyes without SDD, those with SDD were 2.24 (95% confidence interval [CI] 1.36-3.70) times more likely to have AMD at follow-up. After adjusting for age, C-reactive protein quartile, and family history of AMD, the association persisted. CONCLUSIONS: Results suggest that SDD in older eyes with normal macular health as defined by the AREDS scale is a risk factor for the development of early AMD. Older adults in seemingly normal macular health yet having SDD may warrant closer clinical monitoring for the possible onset of early AMD. PMID- 26906161 TI - Antiretroviral Stewardship in a Pediatric HIV Clinic: Development, Implementation and Improved Clinical Outcomes. AB - BACKGROUND: Antiretroviral (ARV) management in pediatrics is a challenging process in which multiple barriers to optimal therapy can lead to poor clinical outcomes. In a pediatric HIV clinic, we implemented a systematic ARV stewardship program to evaluate ARV regimens and make recommendations for optimization when indicated. METHODS: A comprehensive assessment tool was used to screen for issues related to genotypic resistance, virologic/immunologic response, drug-drug interactions, side effects and potential for regimen simplification. The ARV stewardship team (AST) made recommendations to the HIV clinic provider, and followed patients prospectively to assess clinical outcomes at 6 and 12 months. RESULTS: The most common interventions made by the AST included regimen optimization in patients on suboptimal regimens based on resistance mutations (35.4%), switching to safer ARVs (33.3%) and averting significant drug-drug interactions (10.4%). In patients anticipated to have a change in viral load (VL) as a result of the AST recommendations, we identified a significant benefit in virologic outcomes at 6 and 12 months when recommendations were implemented within 6 months of ARV review. Patients who had recommendations implemented within 6 months had a 7-fold higher probability of achieving a 0.7 log10 reduction in VL by 6 months, and this benefit remained significant after controlling for adherence [adjusted odds ratio: 6.8 (95% confidence interval: 1.03-44.9; P <0.05)]. CONCLUSIONS: A systematic ARV stewardship program implemented at a pediatric HIV clinic significantly improved clinical outcomes. ARV stewardship programs can be considered a core strategy for continuous quality improvement in the management of HIV-infected children and adolescents. PMID- 26906162 TI - Incidence of AIDS-defining and Other Cancers in HIV-positive Children in South Africa: Record Linkage Study. AB - BACKGROUND: Little is known on the risk of cancer in HIV-positive children in sub Saharan Africa. We examined incidence and risk factors of AIDS-defining and other cancers in pediatric antiretroviral therapy (ART) programs in South Africa. METHODS: We linked the records of 5 ART programs in Johannesburg and Cape Town to those of pediatric oncology units, based on name and surname, date of birth, folder and civil identification numbers. We calculated incidence rates and obtained hazard ratios (HR) with 95% confidence intervals (CI) from Cox regression models including ART, sex, age and degree of immunodeficiency. Missing CD4 counts and CD4% were multiply imputed. Immunodeficiency was defined according to World Health Organization 2005 criteria. RESULTS: Data of 11,707 HIV-positive children were included in the analysis. During 29,348 person-years of follow-up 24 cancers were diagnosed, for an incidence rate of 82 per 100,000 person-years (95% CI: 55-122). The most frequent cancers were Kaposi sarcoma (34 per 100,000 person-years) and non-Hodgkin Lymphoma (31 per 100,000 person-years). The incidence of non AIDS-defining malignancies was 17 per 100,000. The risk of developing cancer was lower on ART (HR: 0.29; 95% CI: 0.09-0.86), and increased with age at enrollment (>10 vs. <3 years: HR: 7.3; 95% CI: 2.2-24.6) and immunodeficiency at enrollment (advanced/severe versus no/mild: HR: 3.5; 95% CI: 1.1-12.0). The HR for the effect of ART from complete case analysis was similar but ceased to be statistically significant (P = 0.078). CONCLUSIONS: Early HIV diagnosis and linkage to care, with start of ART before advanced immunodeficiency develops, may substantially reduce the burden of cancer in HIV-positive children in South Africa and elsewhere. PMID- 26906163 TI - Treatment of Congenital Toxoplasmosis: Safety of the Sulfadoxine-Pyrimethamine Combination in Children Based on a Method of Causality Assessment. AB - BACKGROUND: The treatment of newborns and infants with congenital toxoplasmosis is standard practice. Some observational studies have examined safety in newborns, but most of these failed to provide sufficient details for a provisional assessment of causality. The aim of this study was to evaluate the clinical and biological adverse effects of the combination of sulfadoxine pyrimethamine. METHODS: Sixty-five children treated for 1 year with a combination of sulfadoxine-pyrimethamine (1 dose every 10 days) for congenital toxoplasmosis were followed up to evaluate abnormal hematological values and potential adverse events using a standardized method of causality assessment. RESULTS: Nine patients (13.8%) presented at least 1 adverse clinical event that was nonspecific, such as diarrhea on the day of drug administration, vomiting and agitation. In 1 patient, erythema appeared at the end of the treatment and resolved within 10 days. None of these events was attributed to the treatment. Six patients (9.2%) developed an adverse hematological event (neutropenia, n = 3; eosinophilia, n = 2 and both anemia and eosinophilia, n = 1) that was considered to be possibly related to the sulfadoxine-pyrimethamine combination. Four treatments were temporarily interrupted, and toxicity was observed after readministration of treatment in 1 case only. However, none of these adverse events was life threatening. CONCLUSIONS: According to our results and previously published data, the combination of sulfadoxine-pyrimethamine seems to be well tolerated. However, the sample size of our study was too small to rule out the risk of less frequent, but nevertheless severe, reactions and, in particular, of hypersensitivity reactions. PMID- 26906164 TI - Does a single bout of resistance or aerobic exercise after insulin dose reduction modulate glycaemic control in type 2 diabetes? A randomised cross-over trial. AB - OBJECTIVES: Regular exercise is advocated for individuals with type 2 diabetes, without fully understanding the acute (0-72h post-exercise) glycaemic response. This study assessed post-exercise glycaemic profiles of non-exercising individuals with insulin treated type 2 diabetes, following resistance and aerobic exercise. DESIGN: Randomised cross-over trial. METHODS: Fourteen individuals with insulin treated type 2 diabetes (9 males, 5 females) aged 58.1+/ 7.1 years (HbA1c: 8.0+/-0.6%) were allocated to single sessions of resistance (six whole-body exercises, three sets, 8-10 repetitions, 70% 1RM) and aerobic (30min cycling, 60% VO2peak) exercise, 7-days apart, with the day prior to the first exercise day of each intervention being the control condition. Immediately prior to exercise, insulin dosage was halved and breakfast consumed. Continuous glucose monitoring was undertaken to determine area under the curve and glucose excursions. RESULTS: Blood glucose initially increased (0-2h) following both resistance and aerobic exercise (p<0.001), peaking at 12.3+/-3.4mmolL(-1) and 12.3+/-3.3mmolL(-1), respectively. Area under the glucose curve was not statistically different over any of the 24h periods (p=0.12), or different in response to resistance (222+/-41mmolL(-1)24h(-1)) or aerobic (211+/-40 mmolL( 1)24h(-1)) exercise (p=0.56). Incidence of hyperglycaemia did not differ between exercise modes (p=0.68). Hypoglycaemic events were identified in three and four participants following resistance and aerobic exercise respectively: these did not require treatment. CONCLUSIONS: Glycaemic response is not different between exercise modes, although 50% insulin dose reduction prior to exercise impairs the expected improvement. A common clinical recommendation of 50% insulin dose reduction does not appear to cause adverse glycaemic events. PMID- 26906165 TI - Single-Chain Antibody Fragment VEGF Inhibitor RTH258 for Neovascular Age-Related Macular Degeneration: A Randomized Controlled Study. AB - PURPOSE: To assess the safety and efficacy of different doses of RTH258 applied as single intravitreal administration compared with ranibizumab 0.5 mg in patients with neovascular age-related macular degeneration (AMD). DESIGN: Six month, phase 1/2, prospective, multicenter, double-masked, randomized, ascending single-dose, active-controlled, parallel-group study. PARTICIPANTS: A total of 194 treatment-naive patients, aged >=50 years, with primary subfoveal choroidal neovascularization secondary to AMD. METHODS: Patients received a single intravitreal injection of RTH258 0.5 mg (n = 11), 3.0 mg (n = 31), 4.5 mg (n = 47), or 6.0 mg (n = 44), or ranibizumab 0.5 mg (n = 61). MAIN OUTCOME MEASURES: The primary efficacy end point was the change from baseline to month 1 in central subfield thickness (CSFT) measured by spectral-domain optical coherence tomography. The secondary efficacy end point was the duration of treatment effect measured as time from the initial injection to receipt of post-baseline therapy (PBT) guided by protocol-defined criteria. Adverse events (AEs) were recorded throughout the study. RESULTS: RTH258 demonstrated noninferiority compared with ranibizumab in mean change in CSFT from baseline to month 1 for the 4.5- and 6.0 mg dose groups (margin: 40 MUm, 1-sided alpha 0.05). The difference in CSFT change at month 1 comparison with ranibizumab was 22.86 MUm (90% confidence interval [CI], -9.28 to 54.99) and 19.40 MUm (95% CI, -9.00 to 47.80) for RTH258 4.5 and 6 mg, respectively. The median time to PBT after baseline therapy was 60 and 75 days for patients in the RTH258 4.5- and 6.0-mg groups, respectively, compared with 45 days for ranibizumab. Changes in best-corrected visual acuity with RTH258 were comparable to those observed with ranibizumab. The most frequent AEs reported for the RTH258 groups were conjunctival hemorrhage, eye pain, and conjunctival hyperemia; the majority of these events were mild in intensity. CONCLUSIONS: This first-in-human study of RTH258 demonstrated noninferiority in the change in CSFT at 1 month for the 4.5- and 6.0-mg doses compared with ranibizumab and an increase of 30 days in the median time to PBT for the 6.0-mg dose. There were no unexpected safety concerns, and the results support the continued development of RTH258 for the treatment of neovascular AMD. PMID- 26906166 TI - Metal ion triggers for reversible switching of DNA polymerase. AB - We herein develop a new strategy that modulates DNA polymerase activity in a reversible and switchable manner by using the novel interactions between DNA bases and metal ions (T-Hg(2+)-T and C-Ag(+)-C) inside a DNA aptamer capable of inhibiting DNA polymerase. PMID- 26906167 TI - Autophagy under attack. AB - Pathogens target proteins involved in autophagy to inhibit immune responses in plants. PMID- 26906168 TI - A new polymorphic form of metoprolol succinate. AB - Only one crystal form of metoprolol succinate (Form I) was reported during previous researches and production. In this study, a new polymorph of metoprolol succinate (here named as Form II) was discovered and investigated by X-ray diffraction, thermoanalysis and infrared spectroscopy. The results show its crystal structure and thermal properties are significantly different with Form I. Compared with Form I, Form II exhibits specific diffraction pattern, lower melting temperature and weaker hydrogen bond effect. The thermostability testing suggests Form II is a metastable crystal form and will gradually transform into Form I undergoing treatment of high temperature and humidity. Metastable crystal form generally has better dissolubility than its corresponding stable form. Subsequent measurement also verified that Form II can dissolve in the water more quickly than Form I. PMID- 26906169 TI - Intra-articular facet joint injections for low back pain: a systematic review. AB - PURPOSE: Evidence supporting the use of therapeutic intra-articular facet joint injections for patients with suspected facet joint pain is sparse. A systematic review including a narrative synthesis was carried out to determine if intra articular facet joint injections with active drug are more effective in reducing back pain and back pain-related disability than a sham procedure or a placebo/inactive injection. Secondly, to determine if intra-articular facet joint injections with active drug or placebo/inactive injection are more effective in reducing back pain and back pain-related disability than conservative treatment. METHODS: Medline, EMBASE, CINAHL, CENTRAL, Index to Chiropractic Literature and the Cochrane Central Register of Controlled Trials were searched from inception through April 2015. Data were screened and single extraction with independent verification and risk of bias assessment was performed. RESULTS: A total of 391 records were screened, and six trials were included. The trials included were small (range 18-109 participants) and overall in terms of pain and disability outcomes most were inconclusive. Only two of the trials report any significant between-group differences in pain (mean difference -1.0, 95% CI -2.0 to -0.1) and (p = 0.032) or disability (mean difference -3.0, 95% CI -6.2 to 0.2) and (p = 0.013) outcomes. CONCLUSIONS: The studies found here were clinically diverse and precluded any meta-analysis. A number of methodological issues were identified. The positive results, whilst interpreted with caution, do suggest that there is a need for further high-quality work in this area. PMID- 26906170 TI - Plasmacytoid dendritic cells and memory T cells infiltrate true sequestrations stronger than subligamentous sequestrations: evidence from flow cytometric analysis of disc infiltrates. AB - PURPOSE: Herniated nucleus pulposus has been considered to induce an adaptive immune response. Antigen recognition by antigen-presenting-cells (APCs) represents an important step within manifestation of an adaptive immune response. Macrophages have been assumed to function as APC, while importance of plasmacytoid dendritic cells for initiation of an immune response directed towards herniated nucleus pulposus has never been examined. The aim of the present study was to assess importance of plasmacytoid dendritic cells for initiation of immune response directed towards herniated discs. METHODS: Fifteen patients with true sequestrations and three patients with subligamentous sequestrations underwent surgery after their neurological examinations. Disc material was harvested, weighted and digested for 90 min. Separated single cells were counted, stained for plasmacytoid dendritic cells (CD123(+)CD4(+)), macrophages (CD14(+)CD11c(+)) and memory T cells (CD4(+)CD45RO(+)) and analysed by flow cytometry. Both patient groups were compared in cell proportions. Furthermore, patients with true sequestrations (TRUE patients) were subdivided into subgroups based on severity of muscle weakness and results in straight leg raising (SLR) test. Subgroups were compared in cell proportions. RESULTS: Plasmacytoid dendritic cells and memory T cells infiltrated true sequestrations stronger than the subligamentous sequestration and plasmacytoid dendritic cells predominated over macrophages in true sequestrations. Highest proportions of plasmacytoid dendritic cells were detected in infiltrates of patients having true sequestrations, severe muscle weakness and negative result in SLR test. CONCLUSIONS: The findings of the present study indicate that plasmacytoid dendritic cells are involved in initiation of an immune response directed towards herniated nucleus pulposus, while macrophages may reinforce the manifested immune response and mediate disc resorption. PMID- 26906171 TI - A comparison of anterior cervical discectomy and fusion (ACDF) using self-locking stand-alone polyetheretherketone (PEEK) cage with ACDF using cage and plate in the treatment of three-level cervical degenerative spondylopathy: a retrospective study with 2-year follow-up. AB - PURPOSE: To evaluate the clinical efficacy and radiological outcomes of anterior cervical discectomy and fusion (ACDF) using self-locking polyetheretherketone (PEEK) cages for treatment of three-level cervical degenerative spondylopathy. METHODS: Twenty-eight patients underwent three-level ACDF using self-locking stand-alone PEEK cages (group A), and 26 patients underwent three-level ACDF using cages and plate fixation (group B) were reviewed retrospectively. Clinical efficacy was evaluated by pre- and post-operative Japanese Orthopedic Association (JOA) scores and Neck Disability Index (NDI). The operation time, blood loss, surgical results according to Odom's criteria and post-operative dysphagia status were also recorded. Radiological outcomes including fusion, cervical Cobb's lordosis, fused segment angle, disc height, and cage subsidence were assessed. RESULTS: Clinical outcome measures such as dysphagia and fusion rate and the results of surgery evaluated according to Odom's criteria were not statistically significant (P > 0.05) between groups. The operation time was shorter and blood loss was less in group A (P < 0.05). The NDI and JOA scores showed significant improvements in both groups after surgery at each time point (P < 0.05) with no significant difference between groups (P > 0.05). Post-operative cage subsidence, the loss of disc height, cervical lordosis and the fused segment angle were relatively higher in group A than group B (P < 0.05). CONCLUSIONS: ACDF using self-locking stand-alone cages showed similar clinical results as compared to ACDF using cages and plate fixation for the treatment of three-level cervical degenerative spondylopathy. However, potential long-term problems such as cage subsidence, loss of cervical lordosis and fused segment angle post-operatively were shown to be associated with patients who underwent ACDF using self-locking stand-alone cages. PMID- 26906172 TI - Theoretical Analysis of Drug Dissolution: I. Solubility and Intrinsic Dissolution Rate. AB - The first-principles approach presented in this work combines surface kinetics and convective diffusion modeling applied to compounds with pH-dependent solubility and in different dissolution media. This analysis is based on experimental data available for approximately 100 compounds of pharmaceutical interest. Overall, there is a linear relationship between the drug solubility and intrinsic dissolution rate expressed through the total kinetic coefficient of dissolution and dimensionless numbers defining the mass transfer regime. The contribution of surface kinetics appears to be significant constituting on average ~20% resistance to the dissolution flux in the compendial rotating disk apparatus at 100 rpm. The surface kinetics contribution becomes more dominant under conditions of fast laminar or turbulent flows or in cases when the surface kinetic coefficient may decrease as a function of solution composition or pH. Limitations of the well-known convective diffusion equation for rotating disk by Levich are examined using direct computational modeling with simultaneous dissociation and acid-base reactions in which intrinsic dissolution rate is strongly dependent on pH profile and solution ionic strength. It is shown that concept of diffusion boundary layer does not strictly apply for reacting/interacting species and that thin-film diffusion models cannot be used quantitatively in general case. PMID- 26906173 TI - Preparation of a Novel Form of Gelatin With a Three-Dimensional Ordered Macroporous Structure to Regulate the Release of Poorly Water-Soluble Drugs. AB - In this study, a novel three-dimensional ordered macroporous gelatin (3DOMG) was fabricated as a carrier for increasing the solubility of poorly water-soluble drugs, offering sustained release and a high oral bioavailability. Polymethyl methacrylate nanospheres (257 nm) were used as a colloidal plastic framework to synthesize 3DOMG. Fenofibrate (FNB) was selected as a model drug and loaded onto 3DOMG by the adsorption equilibrium method. Detailed characterization showed that the FNB absorbed onto 3DOMG was in a microcrystalline state. A fluorescence experiment and the prepared drug microcrystal network gave further information on the physical state of the drug. A degradation experiment proved that 3DOMG was readily biodegradable. In vitro release testing showed that 3DOMG increased the dissolution rate of FNB and produced a sustained release. An in vivo pharmacokinetic study confirmed that 3DOMG improved the oral bioavailability compared with that of commercial sustained-release capsules. These findings confirm that 3DOMG can be regarded as a promising carrier for an oral drug delivery system. PMID- 26906174 TI - Three-Dimensional Printed PCL-Based Implantable Prototypes of Medical Devices for Controlled Drug Delivery. AB - The goal of the present study was to fabricate drug-containing T-shaped prototypes of intrauterine system (IUS) with the drug incorporated within the entire backbone of the medical device using 3-dimensional (3D) printing technique, based on fused deposition modeling (FDMTM). Indomethacin was used as a model drug to prepare drug-loaded poly(epsilon-caprolactone)-based filaments with 3 different drug contents, namely 5%, 15%, and 30%, by hot-melt extrusion. The filaments were further used to 3D print IUS. The results showed that the morphology and drug solid-state properties of the filaments and 3D prototypes were dependent on the amount of drug loading. The drug release profiles from the printed devices were faster than from the corresponding filaments due to a lower degree of the drug crystallinity in IUS in addition to the differences in the external/internal structure and geometry between the products. Diffusion of the drug from the polymer was the predominant mechanism of drug release, whereas poly(epsilon-caprolactone) biodegradation had a minor effect. This study shows that 3D printing is an applicable method in the production of drug-containing IUS and can open new ways in the fabrication of controlled release implantable devices. PMID- 26906176 TI - Modeling vitamin D insufficiency and moderate deficiency in adult mice via dietary cholecalciferol restriction. AB - PURPOSE: We sought to develop and characterize a model of human vitamin D nutritional insufficiency/deficiency in the adult mouse, which could have broad utility in examining health consequences of this common condition. METHODS: Adult mice were fed diets containing cholecalciferol contents of 0.05 IU/g, 0.25 IU/g, 0.5 IU/g or 1.5 IU/g for four months. We studied induction of steady-state vitamin D insufficiency, and its consequences on primary cholecalciferol metabolite levels, calcium homeostasis, parathyroid physiology, and bone morphology. RESULTS: All diets were well tolerated, without adverse effects on body weight. Diets containing 0.05 IU/g and 0.25 IU/g cholecalciferol significantly lowered serum 25-hydroxyvitamin D levels (median 25OHD, 10.5 ng/ml, and 21.6 ng/ml, respectively), starting as early as one month following initiation of the diets, maintained through the four-month experimental period. The 0.05 IU/g diet significantly decreased 1,25-dihydroxyvitamin D (1,25OH2D) levels (median, 78 pg/ml). Despite these decreased 25OHD and 1,25OH2D levels, the diets did not alter parathyroid gland morphology or parathyroid cell proliferation. There were no statistical differences in the serum total calcium and serum PTH levels among the various dietary groups. Furthermore, the 0.05 IU/g diet did not cause any alterations in the cortical and trabecular bone morphology, as determined by microCT. CONCLUSIONS: The dietary manipulations yielded states of vitamin D insufficiency or modest deficiency in adult mice, with no overtly detectable impact on parathyroid and bone physiology, and calcium homeostasis. This model system may be of value to study health effects of vitamin D insufficiency/deficiency especially on extraskeletal phenotypes such as cancer susceptibility or immune function. PMID- 26906175 TI - Breast cancer stem cell selectivity of synthetic nanomolar-active salinomycin analogs. AB - BACKGROUND: Cancer stem cells (CSCs) have been invoked in resistance, recurrence and metastasis of cancer. Consequently, curative cancer treatments may be contingent on CSC selective approaches. Of particular interest in this respect is the ionophore salinomycin, a natural product shown to be 100-fold more active against CSCs than clinically used paclitaxel. We have previously reported that synthetic salinomycin derivatives display increased activity against breast cancer cell lines. Herein we specifically investigate the CSC selectivity of the most active member in each class of C20-O-acylated analogs as well as a C1-methyl ester analog incapable of charge-neutral metal ion transport. METHODS: JIMT-1 breast cancer cells were treated with three C20-O-acylated analogs, the C1-methyl ester of salinomycin, and salinomycin. The effects of treatment on the CSC related CD44(+)/CD24(-) and the aldehyde dehydrogenase positive (ALDH(+)) populations were determined using flow cytometry. The survival ability of CSCs after treatment was investigated with a colony formation assay under serum free conditions. The effect of the compounds on cell migration was evaluated using wound-healing and Boyden chamber assays. The expression of vimentin, related to mesenchymal traits and expression of E-cadherin and beta-catenin, related to the epithelial traits, were investigated using immunofluorescence microscopy. RESULTS: Treatment with each of the three C20-acylated analogs efficiently decreased the putative CSC population as reflected by reduction of the CD44(+)/CD24(-) and ALDH(+) populations already at a 50 nM concentration. In addition, colony forming efficiency and cell migration were reduced, and the expression of the epithelial markers E-cadherin and beta-catenin at the cell surface were increased. In contrast, salinomycin used at the same concentration did not significantly influence the CSC population and the C1-methyl ester was inactive even at a 20 MUM concentration. CONCLUSIONS: Synthetic structural analogs of salinomycin, previously shown to exhibit increased activity against cancer cells, also exhibited improved activity against CSCs across several assays even at nanomolar concentrations where salinomycin was found inactive. The methyl ester analog of salinomycin, incapable of charge-neutral metal ion transport, did not show activity in CSC assays, lending experimental support to ionophoric stress as the molecular initiating event for the CSC effects of salinomycin and related structures. PMID- 26906178 TI - Which Anthropometric Measure Best Correlates with Neonatal Fat Mass at Birth? AB - Objective Body composition provides additional information than weight alone. There is currently no accepted anthropometric measure of adiposity in infants, yet weight and length data allow calculations of a wide array of indices. The study objective was to identify the anthropometric index which best correlates with neonatal adiposity, by examining the associations between neonatal fat mass and several anthropometric indices of newborn infants. Study Design The sum of skinfolds (SSF), birth weight, and birth length were measured in 94 healthy infants (58% males) born at term to healthy mothers. Several anthropometric indices were calculated, and their relationship with SSF was assessed using linear regression adjusting for gestational age and sex. Results SSF at birth was significantly higher in females compared with males (20.7 +/- 3.3 vs. 18.8 +/- 4.1 mm, p = 0.019). Birth weight, birth weight-for-gestational-age percentile, birth weight percentile, and weight/length ratio had the highest associations with SSF, yet R (2) values were very low, ranging from 16 to 18%. Body mass index (BMI), BMI percentile, ponderal index, and the symmetry index had even lower associations. Conclusion No anthropometric measure can confidently assess fat mass in infants at birth, in accordance with previous research. When body composition data are needed, they should be directly measured. PMID- 26906177 TI - Stiffening hydrogels for investigating the dynamics of hepatic stellate cell mechanotransduction during myofibroblast activation. AB - Tissue fibrosis contributes to nearly half of all deaths in the developed world and is characterized by progressive matrix stiffening. Despite this, nearly all in vitro disease models are mechanically static. Here, we used visible light mediated stiffening hydrogels to investigate cell mechanotransduction in a disease-relevant system. Primary hepatic stellate cell-seeded hydrogels stiffened in situ at later time points (following a recovery phase post-isolation) displayed accelerated signaling kinetics of both early (Yes-associated protein/Transcriptional coactivator with PDZ-binding motif, YAP/TAZ) and late (alpha-smooth muscle actin, alpha-SMA) markers of myofibroblast differentiation, resulting in a time course similar to observed in vivo activation dynamics. We further validated this system by showing that alpha-SMA inhibition following substrate stiffening resulted in attenuated stellate cell activation, with reduced YAP/TAZ nuclear shuttling and traction force generation. Together, these data suggest that stiffening hydrogels may be more faithful models for studying myofibroblast activation than static substrates and could inform the development of disease therapeutics. PMID- 26906179 TI - Brain Maturity and Variation of Oxygen Extraction in Premature Infants. AB - Objectives The ability of the premature brain to extract and use oxygen has not been studied adequately. This study aimed to determine factors that influence fractional tissue oxygen extraction (FTOE) of the brain in premature infants using near-infrared spectroscopy (NIRS) and pulse oximetry. Study Design We prospectively studied FTOE in very low birth weight (BW) infants (< 1,500 g and <= 34 weeks' gestation). Factors affecting FTOE and its variability were examined using bivariate and linear regression models. FTOE variability was measured on two scales: short scales (3-20 seconds) and long scales (20-150 seconds). Results We examined 147 simultaneous NIRS and pulse oximetry recordings that were collected from 72 premature infants (gestational age [GA] = 28 weeks and BW = 1,036 g). In regression models, average FTOE correlated negatively with hemoglobin (Hb) and increased significantly in patients with severe intraventricular hemorrhage/periventricular leukomalacia. Both FTOE short- and long-scale variabilities correlated negatively with GA and positively with postnatal age (PNA). Moreover, FTOE long-scale variability was significantly reduced in infants supported with invasive ventilation. Conclusions In premature infants, cerebral oxygen extraction increased with reduced Hb and severe brain injury. Variability in oxygen extraction showed differential changes with GA and PNAs and was affected by invasive ventilation. PMID- 26906180 TI - Improving Interprofessional Consistency in Electronic Fetal Heart Rate Interpretation. AB - Objective To determine if mandatory online training in electronic fetal monitoring (EFM) improved agreement in documentation between obstetric care providers and nurses on labor and delivery. Methods Health care professionals working in obstetrics at our institution were required to complete a course on EFM interpretation. We performed a retrospective chart review of 701 charts including patients delivered before and after the introduction of the course to evaluate agreement among providers in their documentation of their interpretations of the EFM tracings. Results Agreement between provider and nurse documentation at the time of admission improved for variability and accelerations (variability: 91.1 vs. 98.3%, p < 0.001; and accelerations: 75.2 vs. 87.7%, p < 0.001). Similarly, agreement improved at the time of the last note prior to delivery for documentation of variability and accelerations (variability: 82.1 vs. 90.6%, p = 0.001; and accelerations: 56.7 vs. 68.6%, p = 0.0012). Agreement in interpretation of decelerations both at the time of admission and at the time of delivery increased (86.3 vs. 90.6%, p = 0.0787, and 56.7 vs. 61.1%, p = 0.2314, respectively) but was not significant. Conclusion An online EFM course can significantly improve consistency in multidisciplinary documentation of fetal heart rate tracing interpretation. PMID- 26906181 TI - Neonatal Nasopharyngeal Colonization with Group B Streptococcus and its Association with Clinical Sepsis. AB - Objective This study aims to determine whether nasopharyngeal (NP) colonization with group B streptococcus (GBS) is associated with early-onset clinical sepsis within 72 hours of birth, prolonged antibiotic duration, longer neonatal intensive care unit (NICU) stay, and delay in tolerating full feeds among neonates >= 35 weeks gestation. Study Design A retrospective cohort study of 192 NICU neonates admitted for sepsis evaluation. Based on their GBS colonization status, the mother-neonate pairs were divided into four groups of mother-negative neonate (baby)-positive (MNBP), mother-positive neonate-positive (MPBP), mother positive neonate-negative (MPBN), and a reference group of mother-negative neonate-negative (MNBN). Neonates with GBS-positive blood cultures were excluded. Results The colonized neonate groups of MNBP (odds ratio [OR]: 21.8, 95% confidence interval [CI]: 7.99, 59.44) and MPBP (OR: 35.5, 95% CI: 9.57, 131.70) were each associated with increased odds for clinical sepsis (p < 0.001). A similar pattern occurred for prolonged antibiotic use. MPBP group was associated with the increased NICU stay (adjusted beta: 0.1, standard error = 0.05, p < 0.01). None of the GBS groups were associated with increased days to full feeds. Conclusion Neonatal NP GBS colonization was found among a substantial proportion of GBS-negative mothers and was associated with an increased diagnosis of clinical sepsis. PMID- 26906182 TI - Altered Platelet Function in Intrauterine Growth Restriction: A Cause or a Consequence of Uteroplacental Disease? AB - Objective A limited number of platelet function studies in intrauterine growth restriction (IUGR) have yielded conflicting results. We sought to evaluate platelet reactivity in IUGR using a novel platelet aggregation assay. Study Design Pregnancies with IUGR were recruited from 24 weeks' gestation (estimated fetal weight < 10th centile) and had platelet function testing performed after diagnosis. A modification of light transmission aggregometry created dose response curves of platelet reactivity in response to multiple agonists at differing concentrations. Findings were compared with healthy third trimester controls. IUGR cases with a subsequent normal birth weight were analyzed separately. Results In this study, 33 pregnancies retained their IUGR diagnosis at birth, demonstrating significantly reduced platelet reactivity in response to all agonists (arachidonic acid, adenosine diphosphate, collagen, thrombin receptor-activating peptide, and epinephrine) when compared with 36 healthy pregnancy controls (p < 0.0001). Similar results were obtained for cases demonstrating an increasing in utero growth trajectory. When IUGR preceded preeclampsia or gestational hypertension, platelet function was significantly reduced compared with normotensive IUGR. Conclusion Using this comprehensive platelet assay, we have demonstrated a functional impairment of platelets in IUGR. This may reflect platelet-derived placental growth factor release. Further evaluation of platelet function may aid in the development of future platelet targeted therapies for uteroplacental disease. PMID- 26906183 TI - Fetal Sex Differences in Intrapartum Electronic Fetal Monitoring. AB - Objective The article aimed to estimate differences in electronic fetal monitoring (EFM) patterns in term gestations attributable to fetal sex. Study Design We conducted a prospective cohort study of consecutive, singleton, nonanomalous, term gestations that labored during admission. EFM characteristics in the 30 minutes prior to delivery were evaluated. Logistic regression models estimated adjusted risks for EFM features by sex. To further estimate the impact of sex, we limited the analysis to gestations without composite morbidity (morbidity defined as arterial cord pH <7.20, 5-minute Apgar <7, or neonatal intensive care unit admission). Results Of 2,639 deliveries, 1,400 (53%) were male. Male fetuses had a higher number of decelerations (median [interquartile range]: 8 [5, 11] vs. 7 [4, 10], p < 0.003) and increased total deceleration area (adjusted odds ratio [aOR]: 1.11, 95% confidence interval [CI] :1.04, 1.18). Male fetuses were at increased risk for prolonged decelerations (aOR: 1.21, 95% CI: 1.03, 1.42) and repetitive variable decelerations (aOR: 1.24, 95% CI: 1.05, 1.47). Among neonates without composite morbidity (n = 2,446, 92.7%), male sex conferred an increased risk of late decelerations (aOR: 1.21, 95% CI: 1.02, 1.43) and increased total deceleration area (aOR: 1.12, 95% CI: 1.05, 1.20). Conclusion There are significant sex differences in EFM patterns at term among pregnancies without evidence of acidemia. This suggests that interpretation of EFM patterns may need to take into account factors such as fetal sex. PMID- 26906184 TI - Low-Dose Aspirin in Early Gestation for Prevention of Preeclampsia and Small-for Gestational-Age Neonates: Meta-analysis of Large Randomized Trials. AB - Objectives Meta-analyses of small to moderate size randomized controlled trials (RCTs) suggested that aspirin started before 17 weeks' gestation reduces the risk of preeclampsia and small-for-gestational-age (SGA) neonates. We evaluated data from large randomized trials originally excluded from meta-analyses. Methods We performed meta-analyses of RCTs including more than 350 participants that compared aspirin to placebo during pregnancy. Corresponding authors were contacted to obtain data according to gestational age. Outcomes included preeclampsia, severe preeclampsia, and SGA. Relative risks (RRs) with their 95% confidence intervals (CIs) were calculated. Results Data for women recruited before 17 weeks' gestation were obtained for three (50%) of the six eligible trials for a total of 11,949 participants including 3,293 recruited before 17 weeks' gestation with available data. We observed no impact of low-dose aspirin (60 mg) started before 17 weeks' gestation on the risk of preeclampsia (RR: 0.93; 95% CI: 0.75-1.15), severe preeclampsia (RR: 0.96; 95% CI: 0.71-1.28), or SGA (RR: 0.84; 95% CI: 0.56-1.26) and it was not statistically different than when started at or after 17 weeks' gestation. Conclusion Data from large randomized trials do not support greater benefits of low-dose aspirin (at 60 mg daily) when started before 17 weeks' gestation for the prevention of preeclampsia or SGA. PMID- 26906185 TI - Maternal and Perinatal Outcomes in Women with Insulin Resistance. AB - Objective This study aims to estimate the risks of adverse maternal and perinatal outcomes in women with insulin resistance below the threshold of gestational diabetes mellitus (GDM). Methods This was a retrospective cohort study of 5,983 women with singleton pregnancies undergoing universal GDM screening between 24 and 28 weeks gestation. Subjects were divided into those with a normal 1-hour glucose challenge test (GCT), those with an elevated GCT with all normal values on a 3-hour glucose tolerance test (GTT), and those with an elevated GCT with one abnormal value on GTT. Outcomes included macrosomia, pregnancy-induced hypertension (PIH), cesarean section and operative delivery, shoulder dystocia, indicated-preterm birth, and other neonatal outcomes. Logistic regression was performed to compare outcomes among groups. Results The risk of macrosomia was increased for those with an elevated GCT and all normal values on GTT (adjusted odds ratio [aOR], 1.71; 95% confidence interval [CI]: 1.12, 1.97), and for those with an elevated GCT and one abnormal value (aOR, 2.69; 95% CI: 1.49, 4.83). Risks of PIH, cesarean section, and indicated-preterm birth were also increased in those with an elevated 1-hour GCT and no GDM. Conclusion There are increased risks of macrosomia, PIH, indicated-preterm birth, and cesarean section among those with insulin resistance even in the absence of GDM. PMID- 26906186 TI - Clefting of the Alveolus: Emphasizing the Distinction from Cleft Palate. AB - Oral clefting is one of the most common significant fetal abnormalities. Cleft lip and cleft palate have drastically different clinical ramifications and management from one another. A cleft of the alveolus (with or without cleft lip) can confuse the diagnostic picture and lead to a false assumption of cleft palate. The cleft alveolus should be viewed on the spectrum of cleft lip rather than be associated with cleft palate. This is made evident by understanding the embryological development of the midface and relevant terminology. Cleft alveolus carries significantly different clinical implications and treatment options than that of cleft palate. Accurately distinguishing cleft alveolus from cleft palate is crucial for appropriate discussions regarding the patient's care. PMID- 26906187 TI - Phlebotomine sand flies (Diptera: Psychodidae) transmitting visceral leishmaniasis and their geographical distribution in China: a review. AB - After the existence of phlebotomine sand flies was first reported in China in 1910, the distribution of different species and their role in the transmission of visceral leishmaniasis (VL) have been extensively studied. Up until 2008, four species have been verified as vectors of VL, namely, Phlebotomus chinensis (Ph. sichuanensis), Ph. longiductus (Ph. chinensis longiductus), Ph. wui (Ph. major wui), and Ph. alexandri. The sand fly species vary greatly depending on the natural environments in the different geographic areas where they are endemic. Ph. chinensis is euryecious and adaptable to different ecologies, and is thus distributed widely in the plain, mountainous, and Loess Plateau regions north of the Yangtze River. Ph. longiductus is mainly distributed in ancient oasis areas south of Mt. Tianshan in the Xinjiang Uygur autonomous region. Ph. wui is the predominant species in deserts with Populus diversifolia and Tamarix vegetation in Xinjiang and the western part of the Inner Mongolia autonomous region. Finally, Ph. alexandri is steroecious and found only in stony desert areas, such as at the foot of the mountains in Xinjiang and the western Hexi Corridor, in Gansu province. This review summarized the relationship between the geographic distribution pattern of the four sand fly species and their geographical landscape in order to foster research on disease distribution and sand fly control planning. Furthermore, some problems that remained to be solved about vectors of VL in China were discussed. PMID- 26906188 TI - Efficacy of 5-aminolevulinic acid based photodynamic therapy in pituitary adenomas-experimental study on rat and human cell cultures. AB - BACKGROUND: Incomplete resection of pituitary adenomas may result in recurrence. As adjuvant irradiation is not riskless, alternative treatment options should be investigated. 5-aminolevulinic acid based photodynamic therapy (5-ALA based PDT) showed promising results for malignant gliomas. The present study examined the efficacy of 5-ALA PDT in vitro on benign pituitary adenoma cell cultures. METHODS: In group I experiments were performed on immortalized rat pituitary adenoma cells (GH3). The cultured cells were treated with different 5-ALA concentrations ranging from 7.5-16.5MUg/ml. In Group II human pituitary adenoma cell cultures were obtained from surgically resected adenoma tissue (n=15). These were incubated with 5-ALA concentrations from 12.5-100MUg/ml. The concentration ranges had been determined in preliminary dose-finding tests. For both groups incubation time was four hours and PDT was performed by exposition to laser light (635nm, 625s, 18.75J/cm(2)). Cell viability was examined by WST-1 assay. RESULTS: In both groups PDT showed a 5-ALA concentration-dependent effect on cell death. In group I lower 5-ALA concentrations were necessary to destroy all cells as compared to group II. Moreover, in group II, the different subtypes of human adenomas showed different sensitivities to 5-ALA-based PDT (secreting vs. non secreting). Especially corticotroph adenomas were highly sensitive to 5-ALA PDT. CONCLUSIONS: The GH3 cell line was an useful in vitro model to optimize different PDT parameters. Human pituitary adenoma cells could also be killed by 5-ALA PDT, however this required higher 5-ALA concentrations. Furthermore, the results suggested different 5-ALA sensitivities between different human adenoma cell types. More experiments are necessary to confirm these preliminary results. PMID- 26906189 TI - The value of a multiplexed gastrointestinal pathogen panel in 2 distinct patient populations. AB - We assess the value of the Luminex xTAG Gastrointestinal Pathogen Panel (GPP) in 2 different patient populations: an uninsured, indigent population seeking primary care, and a tertiary care hospital specializing in surgical, transplant, and oncology care. Stool specimens collected April to August 2013 for infectious workup were tested on the GPP, and discordant results were further analyzed by alternative methods. Compared to the tertiary care setting, stool pathogen detection was nearly twice as frequent in the primary care setting (25% versus 14%; P<0.05) with a broader array of pathogens detected (15 versus 4). Overall, the greatest value of the GPP was in detection of viral causes of gastroenteritis that were not routinely sought and in detection of Campylobacter spp. when patients presented late in the disease course. Application of a GPP should consider the characteristics of the patient population to maximize its clinical utility in different healthcare settings. PMID- 26906190 TI - In vitro activity of tedizolid against staphylococci isolated from prosthetic joint infections. AB - We determined the MIC and minimum biofilm bactericidal concentration (MBBC) of tedizolid and vancomycin against 97 isolates of Staphylococcus aureus and 74 isolates of Staphylococcus epidermidis associated with prosthetic joint infection. All isolates were vancomycin susceptible in the planktonic state; all staphylococci studied had a tedizolid MIC <=0.5 MUg/mL. The MBBC90 was >32 and >128 MUg/mL for tedizolid and vancomycin, respectively. PMID- 26906191 TI - Morbidity and mortality attributable to Rothia bacteremia in neutropenic and nonneutropenic patients. AB - Rothia spp. are increasingly being recognized as emerging opportunistic pathogens associated with serious infections in immune-compromised hosts. Risk factors include neutropenia, hematologic malignancies, prosthetic devices, and intravascular catheters. We describe 29 patients at our institute from 2006 to 2014 with positive blood cultures for Rothia spp. Neutropenia was observed in 21/29 (72%) patients at the time of bacteremia, and 16/29 (61%) had leukemia. Neutropenic patients were less likely than nonneutropenic patients to have polymicrobial infection (24% versus 63%; P= 0.083) and were also more likely to have multiple positive blood cultures (76% versus 0%; P= 0.0003), indicating true infection. Sources of bacteremia included intravascular catheters, mucositis, and presumed gut translocation. A significant association was seen with steroid use (81% versus 13%; P= 0.0014) and fluoroquinolone use (86% versus 13%; P<= 0.0001) preceding bacteremia in neutropenic patients. There was no difference between the 2 groups for admission to intensive care unit or mortality. One death was reported possibly due to Rothia infection. PMID- 26906192 TI - Recurrent bacteremia with Streptococcus dysgalactiae: a case-control study. AB - Beta-hemolytic streptococci of groups C and G, designated as Streptococcus dysgalactiae (SD), can cause severe and recurring invasive infections. In this case-control study, we aimed to identify clinical and molecular risk factors for recurrence of SD bacteremia. Twenty-two cases of recurrent SD bacteremia were identified, and median time between episodes was 6 months. The most frequent clinical manifestation was skin and soft tissue infection. Cases and 92 controls, with single-episode SD bacteremia, showed similar demographics, had similar Charlson comorbidity scores, and had similar clinical presentations. Thirty-day fatality was 13% among controls, whereas none of 22 cases died. In 19 cases (86%), the same emm type was encountered in both episodes. SD isolates from recurrent episodes and from single episodes had a similar emm type distribution. Thus, we did not identify clinical risk factors for recurrences. The high proportion of identical emm types in recurrent episodes indicates a host-specific colonization. PMID- 26906194 TI - Erratum to: Pulmonary Hemodynamics Simulations Before Stage 2 Single Ventricle Surgery: Patient-Specific Parameter Identification and Clinical Data Assessment. PMID- 26906193 TI - Seasonal variation in harbour seal (Phoca vitulina) blubber cortisol - A novel indicator of physiological state? AB - Cortisol is one of the main glucocorticoid hormones involved in both the mammalian stress response, and in fat metabolism and energy regulation, making it of increasing interest as a biomarker for stress, health and overall physiological state. However, transient stress responses to animal handling and sampling may be important sources of measurement artefact when investigating circulating concentrations of this hormone in wildlife. Here, cortisol concentrations were measured in the plasma and, for the first time, in the blubber of live captured adult harbour seals (Phoca vitulina). Plasma cortisol concentrations were positively correlated with capture time, suggesting that they were largely driven by a stress response to the capture event. In contrast, blubber cortisol concentrations were shown not to be significantly affected by capture time and varied significantly by sex and by season, with higher concentrations during natural fasting periods of their life cycle, particularly during the moult. These results suggest that cortisol may play a key role in increased fat metabolism during highly energetically demanding periods, and that blubber concentrations have the potential to be used as physiological state indicators in phocid seals. PMID- 26906195 TI - Role of Hematopoietic Stem Cells in Inflammation of the Pancreas during Diabetes Mellitus. AB - The model of streptozotocin-induced diabetes mellitus in C57Bl/6 mice was employed to study the role of precursors of insulin-producing beta-cells, hematopoietic stem cells, and progenitor hematopoietic cells in inflammation. In addition to provoking hyperglycemia, streptozotocin elevated serum levels of IL 1beta and hyaluronic acid, induced edema in the pancreatic insular tissue and its infiltration by inflammatory cells (neutrophils, lymphocytes, and macrophages) and fibroblasts. Inflammation in pancreatic islets was accompanied by necrotic processes and decreasing counts of multipotent progenitor beta-cells (CD45(-), TER119(-), c-kit-1(-), and Flk-1(-)), oligopotent progenitor beta-cells (CD45(-), TER119(-), CD133(+), and CD49f(low)), and insulinproducing beta-cells (Pdx1(+)). Pancreatic infl ammation was preceded by elevation of the number of short-term hematopoietic stem cells (Lin-Sca-1(+)c-kit(+)CD34(+)) relative to long-term cells (Lin(-)Sca-1(+)c-kit(+)CD34(-)) in the bone marrow as well as recruitment of hematopoietic stem and progenitor cells into circulation. Transplantation of bone marrow hematopoietic stem and progenitor cells from diabetic C57Bl/6 donor mice to recipient CBA mice with 5-fluorouracilinduced leukopenia accelerated regeneration of granulocytopoiesis in recipient mice. PMID- 26906196 TI - Interleukin-1beta Can Reduce Manifestations of Delayed Effects of Prolonged Exposure to Low-Intensity gamma-Radiation. AB - We showed that injection of IL-1beta (Betaleukin) in a dose of 3 MUg/kg 22 h before prolonged (21 h) exposure to low-intensity (10 mGy/min) gamma-radiation in a dose of 12.6 Gy reduced the number of double-strand DNA breaks in murine spleen cells to the control level in 4 months after exposure and the number of double strand DNA breaks induced by additional acute irradiation in a dose of 6 Gy. The results suggest that IL-1beta can improve the efficiency of systems reducing the number of double-strand DNA breaks in murine spleen cells at delayed terms after exposure to prolonged low-intensity radiation. PMID- 26906197 TI - Ingramon, a Peptide Inhibitor of MCP-1 Chemokine, Reduces Migration of Blood Monocytes Stimulated by Glioma-Conditioned Medium. AB - Malignant gliomas are most common and fatal primary brain tumors. In addition to neoplastic cells, the tumor tissue contains microglial cells and monocyte-derived macrophages. It is an established fact that monocyte recruiting promotes the tumor growth and dissemination. Monocyte chemotactic protein-1 (MCP-1) is the major attractant for monocytes. We have previously synthesized an MCP-1 antagonist ingramon, a synthetic peptide fragment (65-76) of this chemokine. In the present study, we demonstrated that glioma-conditioned medium contains MCP-1 and stimulates migration of blood monocytes. Ingramon inhibited the effect of glioma-conditioned medium on monocyte migration. PMID- 26906198 TI - Comparison of Nootropic and Neuroprotective Features of Aryl-Substituted Analogs of Gamma-Aminobutyric Acid. AB - GABA analogs containing phenyl (phenibut) or para-chlorophenyl (baclofen) substituents demonstrated nootropic activity in a dose of 20 mg/kg: they improved passive avoidance conditioning, decelerated its natural extinction, and exerted antiamnestic effect on the models of amnesia provoked by scopolamine or electroshock. Tolyl-containing GABA analog (tolibut, 20 mg/kg) exhibited antiamnestic activity only on the model of electroshock-induced amnesia. Baclofen and, to a lesser extent, tolibut alleviated seizures provoked by electroshock, i.e. both agents exerted anticonvulsant effect. All examined GABA aryl derivatives demonstrated neuroprotective properties on the maximum electroshock model: they shortened the duration of coma and shortened the period of spontaneous motor activity recovery. In addition, these agents decreased the severity of passive avoidance amnesia and behavioral deficit in the open field test in rats exposed to electroshock. The greatest neuroprotective properties were exhibited by phenyl-containing GABA analog phenibut. PMID- 26906199 TI - Assessment of Functional Disturbances in the Central Nervous System Caused by Severe Carbon Monoxide Poisoning in Rats. AB - An experimental model was developed for assessment of disturbances in CNS functions of laboratory animals caused by severe carbon monoxide poisoning. Normalization of the state of experimental rats after acute poisoning was accompanied by the development of cognitive abnormalities. Disturbances in the long-term memory were observed on days 1 and 14 after CO poisoning, while abnormalities in the short-term memory developed on days 1, 7, and 14. Learning impairment were recorded on day 8, while the training course began on day 7. PMID- 26906200 TI - Effects of 5-Pyrimidinol Derivative SNK-41 on Cytokine Profile of Mice with Lewis Lung Carcinoma. AB - We studied the effects of SNK-411, a new 5-pyrimidinol derivative, on serum cytokine profile of C57Bl/6 mice with Lewis lung carcinoma. The compound was injected intraperitoneally in doses of 25 and 50 mg/kg. A significant (by 3.5 times) increase in serum IL-4 content was detected in mice with tumors on day 9 of tumor development. In mice receiving SNK-411 in doses of 25 and 50 mg/kg, IL-4 content significantly decreased (by 4.0 and 3.6 times) on days 2-8 of carcinoma development; IL-2 content decreased by 1.4 and 1.2 times and IL-6 content decreased by 2.7 and 1.6 times, respectively, in comparison with control mice with tumors. Injections of SNK-411 in the same doses on days 8-15 of carcinoma development led to a significant decrease in IL-4 levels (by 2.2 and 4.5 times, respectively, in comparison with control mice with tumors) and did not affect serum levels of other cytokines. PMID- 26906201 TI - Toxic Effects of Lithium Chloride during Early Neonatal Period of Rat Development. AB - Lithium chloride (85, 255, or 255+127 MUg/kg) or dexamethasone (0.2 or 2 mg/kg) were subcutaneously injected to 3-day-old rat pups, whose excretory system did not yet attain functional maturity. Both agents retarded the growth of rat pups and delayed the appearance of negative geotaxis. LD50 and therapeutic index of lithium chloride were 255 MUg/kg and TI<=3, respectively. Thus, lithium salts even in low doses can be highly toxic for the developing organism. PMID- 26906202 TI - Changes in Cell Composition of Umbilical Cord Blood and Functional Activity of Hematopoietic Stem Cells during Cryogenic Storage and Repeated Freezing/Thawing Cycles. AB - We analyzed changes in cell composition of umbilical cord blood and functional activity of hematopoietic stem cells during cryogenic storage and after repeated freezing/thawing cycles. It was found that repeated freezing/thawing cycles performed according to the optimal programmable freezing protocol did not significantly affect viability and functional activity of hematopoietic stem cells. When fast freezing program was used, the cells completely lost their capacity to form colonies in semisolid medium, despite high viability parameters in the test with 7-AAD. PMID- 26906203 TI - Transplantation of Simian Mesenchymal Stem Cells to Baboons with Experimentally Induced Myocardial Infarction. AB - Culture of mesenchymal stem cells isolated from the bone marrow of primates by their characteristics met the requirements of stem cells. It was shown that transplantation of allogeneic mesenchymal stem cells (2 million cells per 1 kg body weight) immediately after ligation of the left anterior descending coronary artery between the middle and upper thirds led to neovascularization and capillarization of the ischemic myocardium. PMID- 26906204 TI - Modulation of PBMC-decay accelerating factor (PBMC-DAF) and cytokines in rheumatoid arthritis. AB - Studies have suggested that abnormal expression of complement regulatory proteins and cytokines contribute significantly to the path-physiology of rheumatoid arthritis. In this context, Decay accelerating factor (DAF) a complement regulatory protein is gaining increased attention. With the notion that immune effecter mechanisms are all interlinked and circulating peripheral blood mononuclear cells (PBMCs) should have a role in a systemic disease like rheumatoid arthritis, we studied the modulation and significance of PBMC-DAF and cytokines in RA. Seventy-five RA patients and 75 healthy controls were recruited. Expression of DAF and cytokines (IFN-gamma, IL-17A and IL-10) in the PBMCs of patients and controls was determined. Correlations among DAF, cytokines, and disease activity were evaluated by standard statistical methods. The effect of IFN-gamma, IL-17A, and IL-10 on the expression of DAF in patients and controls was studied in vitro. Expression of PBMC-DAF declined in patients both at mRNA and surface level and correlated negatively with the disease activity. Expression of IFN-gamma also declined in patients but correlated positively with DAF and negatively with disease activity. Expression of IL-17A and IL-10 was higher in patients. The levels correlated positively with disease activity and negatively with DAF both in patients and controls. In vitro studies indicated that IFN-gamma up-regulated DAF expression in PBMCs, whereas IL-17A and IL-10 had negative effect on the same. The decline in the PBMC-DAF is a contributing factor in manifestations of RA. Cytokine environment contributes to this decline. These findings brought novel insights into the complement-cytokine axis in the path physiology of RA. PMID- 26906205 TI - Transcription factor Sp1 prevents TRF2(DeltaBDeltaM)-induced premature senescence in human diploid fibroblasts. AB - Telomere uncapping is thought to be the fundamental cause of replicative cellular senescence, but the cellular machineries mediating this process have not been fully understood. In the present study, we present the role of Sp1 transcription factor in the state of telomere uncapping using the TRF2(DeltaBDeltaM)-induced senescence model in human diploid fibroblasts. We observed that the expression of Sp1 is down-regulated in the TRF2(DeltaBDeltaM)-induced senescence, which was mediated by ATM and p38 MAPK. In addition, overexpression of Sp1 prevented the TRF2(DeltaBDeltaM)-induced senescence. Among transcriptional targets of Sp1, expression levels of nuclear transport genes such as karyopherin alpha, Nup107, and Nup50 were down-regulated in the TRF2(DeltaBDeltaM)-induced senescence, which was prevented by Sp1 overexpression. Moreover, inhibition of the nuclear transport by wheat germ agglutinin (an import inhibitor) and leptomycin B (an export inhibitor) induced premature senescence. These results suggest that Sp1 is an anti-senescence transcription factor in the telomere uncapping-induced senescence and that down-regulation of Sp1 leads to the senescence via down regulation of the nuclear transport. PMID- 26906208 TI - [Not Available]. PMID- 26906206 TI - Bordetella pertussis: new concepts in pathogenesis and treatment. AB - PURPOSE OF REVIEW: The purpose of this review is to summarize and discuss recent findings and selected topics of interest in Bordetella pertussis virulence and pathogenesis and treatment of pertussis. It is not intended to cover issues on immune responses to B. pertussis infection or problems with currently used pertussis vaccines. RECENT FINDINGS: Studies on the activities of various B. pertussis virulence factors include the immunomodulatory activities of filamentous hemagglutinin, fimbriae, and adenylate cyclase toxin. Recently emerging B. pertussis strains show evidence of genetic selection for vaccine escape mutants, with changes in vaccine antigen-expressing genes, some of which may have increased the virulence of this pathogen. Severe and fatal pertussis in young infants continues to be a problem, with several studies highlighting predictors of fatality, including the extreme leukocytosis associated with this infection. Treatments for pertussis are extremely limited, though early antibiotic intervention may be beneficial. Neutralizing pertussis toxin activity may be an effective strategy, as well as targeting two host proteins, pendrin and sphingosine-1-phosphate receptors, as novel potential therapeutic interventions. SUMMARY: Pertussis is reemerging as a major public health problem and continued basic research is revealing information on bacterial virulence and disease pathogenesis, as well as potential novel strategies for vaccination and targets for therapeutic intervention. PMID- 26906209 TI - [Competence-based catalogue of learning objectives for conducting medical consultations]. AB - ISSUE: In 2012 the German medical licensure regulations (Approbationsordnung) made teaching and assessing the conduction of medical consultations a mandatory part of medical education. A catalogue of learning objectives (LO) based on existing references was developed to assist medical schools in meeting this requirement. METHODS: A body of relevant material was compiled using literature research and surveying experts. Then, in a multiphase Delphi process, this was evaluated and condensed by an interdisciplinary working group in dialogue with external (clinical) experts. Competence levels and examples of clinical application were assigned to enhance implementation. The catalogue was revised by the medical faculties, professional associations and the BVMD. RESULTS: This learning catalogue comprised 116 learning objectives for the specific skills necessary to conducting medical consultations as well as exemplary application contexts. The catalogue proved to be practical in terms of developing curricula and networking at medical schools. DISCUSSION: This catalogue of learning objectives can serve as the basis for developing a sample communication curriculum for use by medical faculties. PMID- 26906210 TI - Heart Rate Variability during Inpatient Psychosomatic Treatment - A Naturalistic Observational Study. AB - OBJECTIVES: We tested the hypothesis that inpatient psychosomatic treatment would improve both psychological distress and autonomic dysfunction, indexed as heart rate variability (HRV). METHODS: 135 patients (mean age 47.2 years, 68.1% women) were enrolled. The most frequent diagnoses were somatoform disorders, adjustment disorders, major depression, eating disorders, and anxiety disorders.Mean duration of treatment was 21.8 +/- 7.3 days. Complete HRV data were available on 105 patients. RESULTS: At the beginning of the treatment, psychological distress correlated with the low frequency/ high frequency ratio of HRV, indicating a shift of autonomic balance towards sympathetic predominance. Following treatment, psychological distress had improved, but parasympathetic activity was even lower. Tricyclic antidepressant use was associated with an increase in heart rate. No other associations between antidepressant use and autonomic function were observed. CONCLUSIONS: Reductions of psychological distress may not be reflected by improved autonomic function. Studies on interventions that may improve both psychological distress and autonomic dysfunction are desirable. PMID- 26906216 TI - Exploiting Copper Redox for (19)F Magnetic Resonance-Based Detection of Cellular Hypoxia. AB - We report a pair of fluorinated, redox-active copper complexes for potential use as (19)F MRI contrast agents for detecting cellular hypoxia. Trifluorinated Cu(II) ATSM-F3 displays the appropriate redox potential for selective accumulation in hypoxic cells and a completely quenched (19)F NMR signal that is "turned on" following reduction to Cu(I). Incubation of cancer cells with CuATSM F3 resulted in a selective detection of (19)F signal in cells grown under hypoxic conditions. PMID- 26906215 TI - Inhibitory effect of traditional oriental medicine-derived monoamine oxidase B inhibitor on radioresistance of non-small cell lung cancer. AB - Increased survival of cancer cells mediated by high levels of ionizing radiation (IR) reduces the effectiveness of radiation therapy for non-small cell lung cancer (NSCLC). In the present study, danshensu which is a selected component of traditional oriental medicine (TOM) compound was found to reduce the radioresistance of NSCLC by inhibiting the nuclear factor-kappaB (NF-kappaB) pathway. Of the various TOM compounds reported to inhibit the IR activation of NF kappaB, danshensu was chosen as a final candidate based on the results of structural comparisons with human metabolites and monoamine oxidase B (MAOB) was identified as the putative target enzyme. Danshensu decreased the activation of NF-kappaB by inhibiting MAOB activity in A549 and NCI-H1299 NSCLC cells. Moreover, it suppressed IR-induced epithelial-to-mesenchymal transition, expressions of NF-kappaB-regulated prosurvival and proinflammatory genes, and in vivo radioresistance of mouse xenograft models. Taken together, this study shows that danshensu significantly reduces MAOB activity and attenuates NF-kappaB signaling to elicit the radiosensitization of NSCLC. PMID- 26906218 TI - Incipient UV-Induced Structural Changes in Neutrophil Granulocytes: Morphometric and Texture Analysis of Two-Dimensional Digital Images. AB - The aim of this study is to determine the ability and consequent significance of fractal and lacunarity analysis together with computational morphometric and gray level co-occurrence matrix (GLCM) analysis in detecting subtle initial UVB induced chromatin and cytosolic changes in neutrophil granulocytes. In addition, the direction and potential significance of the observed changes is speculated. Feulgen-stained neutrophils are pictured and their digitalized images are analyzed in specialized software for digital image processing and ImageJ analysis. Significant statistical difference is observed (p0.05). For other parameters there was mostly high statistical significance (p>0.05). Significant unmatched correlations were found as sensitive markers of early morphological changes in cells exposed to UV light. In addition, the correlation between nuclear area and entropy was determined and was highly significant (p<0.001). UVB light, due to its high absorbance by DNA molecules, leads to double behavior of the cells. On one hand, cells start to rearrange but on the other UV light starts very early to immediately damage the cell. All these processes are very subtle in their intensity and GLCM analysis and computational imaging methods based on fractal geometry, i.e. fractal and morphometric analysis, in particular their combination, are very sensitive for detecting and describing these early chromatin changes. PMID- 26906217 TI - Anticoagulation Management Practices and Outcomes in Elderly Patients with Acute Venous Thromboembolism: A Clinical Research Study. AB - Whether anticoagulation management practices are associated with improved outcomes in elderly patients with acute venous thromboembolism (VTE) is uncertain. Thus, we aimed to examine whether practices recommended by the American College of Chest Physicians guidelines are associated with outcomes in elderly patients with VTE. We studied 991 patients aged >=65 years with acute VTE in a Swiss prospective multicenter cohort study and assessed the adherence to four management practices: parenteral anticoagulation >=5 days, INR >=2.0 for >=24 hours before stopping parenteral anticoagulation, early start with vitamin K antagonists (VKA) <=24 hours of VTE diagnosis, and the use of low-molecular weight heparin (LMWH) or fondaparinux. The outcomes were all-cause mortality, VTE recurrence, and major bleeding at 6 months, and the length of hospital stay (LOS). We used Cox regression and lognormal survival models, adjusting for patient characteristics. Overall, 9% of patients died, 3% had VTE recurrence, and 7% major bleeding. Early start with VKA was associated with a lower risk of major bleeding (adjusted hazard ratio 0.37, 95% CI 0.20-0.71). Early start with VKA (adjusted time ratio [TR] 0.77, 95% CI 0.69-0.86) and use of LMWH/fondaparinux (adjusted TR 0.87, 95% CI 0.78-0.97) were associated with a shorter LOS. An INR >=2.0 for >=24 hours before stopping parenteral anticoagulants was associated with a longer LOS (adjusted TR 1.2, 95% CI 1.08-1.33). In elderly patients with VTE, the adherence to recommended anticoagulation management practices showed mixed results. In conclusion, only early start with VKA and use of parenteral LMWH/fondaparinux were associated with better outcomes. PMID- 26906227 TI - Effects of nozzle type atmospheric dry air plasma on L929 fibroblast cells hybrid poly (epsilon-caprolactone)/chitosan/poly (epsilon-caprolactone) scaffolds interactions. AB - In the study presented here, in order to improve the surface functionality and topography of poly (epsilon-caprolactone) (PCL)/chitosan/PCL hybrid tissue scaffolds fabricated layer by layer with electrospinning technique, an atmospheric pressure nozzle type plasma surface modification was utilized. The optimization of the plasma process parameters was carried out by monitoring the changes in surface hydrophilicity by using contact angle measurements. SEM, AFM and XPS analyses were utilized to observe the changes in topographical and chemical properties of the modified surfaces. The results showed that applied plasma modification altered the nanotopography and the functionality of the surfaces of the scaffolds. The modification applied for 9 min from a distance of 17 cm was found to provide the possible contact angle value (75.163+/-0.083) closest to the target value which is the value of tissue culture polystyrene (TCPS) petri dishes (~49.7 degrees ), compared to the unmodified samples (84.46+/ 3.86). In vitro cell culture was carried out by L929 mouse fibroblast cell line in order to examine the effects of plasma surface modification on cell-material interactions. Standard MTT assay showed improved cell viability on/within modified scaffolds confirmed with the observations of the cell attachment and the morphology by means of SEM, fluorescence and confocal imaging. The experiments performed in the study proved the enhanced biocompatibility of the nozzle type dry air plasma modified scaffolds. PMID- 26906225 TI - Sustained TNF production by central nervous system infiltrating macrophages promotes progressive autoimmune encephalomyelitis. AB - BACKGROUND: Tumor necrosis factor (TNF) has pleiotropic functions during both the demyelinating autoimmune disease multiple sclerosis (MS) and its murine model experimental autoimmune encephalomyelitis (EAE). How TNF regulates disability during progressive disease remains unresolved. Using a progressive EAE model characterized by sustained TNF and increasing morbidity, this study evaluates the role of unregulated TNF in exacerbating central nervous system (CNS) pathology and inflammation. METHODS: Progressive MS was mimicked by myelin oligodendrocyte glycoprotein (MOG) peptide immunization of mice expressing a dominant negative IFN-gamma receptor alpha chain under the human glial fibrillary acidic protein promoter (GFAPgammaR1?). Diseased GFAPgammaR1? mice were treated with anti-TNF or control monoclonal antibody during acute disease to monitor therapeutic effects on sustained disability, demyelination, CNS inflammation, and blood brain barrier (BBB) permeability. RESULTS: TNF was specifically sustained in infiltrating macrophages. Anti-TNF treatment decreased established clinical disability and mortality rate within 7 days. Control of disease progression was associated with a decline in myelin loss and leukocyte infiltration, as well as macrophage activation. In addition to mitigating CNS inflammation, TNF neutralization restored BBB integrity and enhanced CNS anti-inflammatory responses. CONCLUSIONS: Sustained TNF production by infiltrating macrophages associated with progressive EAE exacerbates disease severity by promoting inflammation and disruption of BBB integrity, thereby counteracting establishment of an anti-inflammatory environment required for disease remission. PMID- 26906226 TI - Identification of Immunoreactive Leishmania infantum Protein Antigens to Asymptomatic Dog Sera through Combined Immunoproteomics and Bioinformatics Analysis. AB - Leishmania infantum is the etiologic agent of zoonotic visceral leishmaniasis (VL) in countries in the Mediterranean basin, where dogs are the domestic reservoirs and represent important elements in the transmission of the disease. Since the major focal areas of human VL exhibit a high prevalence of seropositive dogs, the control of canine VL could reduce the infection rate in humans. Efforts toward this have focused on the improvement of diagnostic tools, as well as on vaccine development. The identification of parasite antigens including suitable major histocompatibility complex (MHC) class I- and/or II-restricted epitopes is very important since disease protection is characterized by strong and long lasting CD8+ T and CD4+ Th1 cell-dominated immunity. In the present study, total protein extract from late-log phase L. infantum promastigotes was analyzed by two dimensional western blots and probed with sera from asymptomatic and symptomatic dogs. A total of 42 protein spots were found to differentially react with IgG from asymptomatic dogs, while 17 of these identified by Coommasie stain were extracted and analyzed. Of these, 21 proteins were identified by mass spectrometry; they were mainly involved in metabolism and stress responses. An in silico analysis predicted that the chaperonin HSP60, dihydrolipoamide dehydrogenase, enolase, cyclophilin 2, cyclophilin 40, and one hypothetical protein contain promiscuous MHCI and/or MHCII epitopes. Our results suggest that the combination of immunoproteomics and bioinformatics analyses is a promising method for the identification of novel candidate antigens for vaccine development or with potential use in the development of sensitive diagnostic tests. PMID- 26906228 TI - Two glycerol 3-phosphate dehydrogenase isogenes from Candida versatilis SN-18 play an important role in glycerol biosynthesis under osmotic stress. AB - Two isogenes of glycerol 3-phosphate dehydrogenase (GPD) from Candida versatilis SN-18 were cloned and sequenced. These intronless genes (Cagpd1 and Cagpd2) were both predicted to encode a 378 amino acid polypeptide, and the deduced amino acid sequences mutually showed 76% identity. Interestingly, Cagpd1 and Cagpd2 were located tandemly in a locus of genomic DNA within a 262 bp interval. To our knowledge, this represents a novel instance of isogenic genes relating to glucose metabolism. The stress response element (STRE) was found respectively at -93 to 89 bp upstream of the 5'end of Cagpd1 and -707 to -703 bp upstream of Cagpd2, indicating that these genes are involved in osmotic stress response. In heterologous expression using a gpd1Deltagpd2Delta double deletion mutant of Saccharomyces cerevisiae, Cagpd1 and Cagpd2 transformants complemented the function of GPD, with Cagpd2 being much more effective than Cagpd1 in promoting growth and glycerol synthesis. Phylogenetic analysis of the amino acid sequences suggested that Cagpd1p and Cagpd2p are NADP(+)-dependent GPDs (EC 1.1.1.94). However, crude enzyme extract from Cagpd1 and Cagpd2 transformants showed GPD activity with only NAD(+) as cofactor. Hence, both Cagpd1p and Cagpd2p are likely NAD(+)-dependent GPDs (EC 1.1.1.8), similar to GPDs from S. cerevisiae and Candida magnoliae. PMID- 26906229 TI - The adrenergic alpha2-receptor, sexual incentive motivation and copulatory behavior in the male rat. AB - Adrenergic alpha2 antagonists are known to enhance sexual incentive motivation and modify copulatory behavior while agonists are consistently inhibitory. However, many of the drugs employed in earlier studies were of modest specificity for the alpha2 receptor, and the importance of the different subtypes of this receptor remains completely unknown. In the present series of experiments we determined the effects on sexual incentive motivation and copulatory behavior of additional, highly specific compounds, as well as of agonists selective for each of the three subtypes of the alpha2 receptor. Sexual incentive motivation and copulatory behavior were evaluated in male rats in well established procedures. Among the alpha2 antagonists, RX 821002 reliably enhanced sexual incentive motivation while fluparoxan only had a modest effect. In large doses both drugs reduced copulatory behavior. The agonist S 18616 reduced both incentive motivation and copulation. None of the subtype selective agonists (BRL 44408, ARC 239, JP 1302) had any consistent effect. A peripheral alpha2 antagonist, L 659,066 was also ineffective. Even though there are some differences between alpha2 antagonists with regard to their effects on sexual incentive motivation and copulatory behavior it seems safe to conclude that antagonism of the adrenergic alpha2 receptor enhances motivation without any concomitant stimulation of copulatory behavior. It appears that antagonism of a single receptor subtype is insufficient for having this effect. Perhaps non-selective alpha2 antagonists could be used for the treatment of male sexual dysfunction. PMID- 26906230 TI - [Etiologies of end-stage renal disease of children in Tunisia]. AB - BACKGROUND: The end-stage renal disease (ESRD) in children has special features in terms of etiologies, therapeutic modalities and access to renal transplantation. In Tunisia, there are no data on the epidemiology of ESRD in children. The aim of our study was to describe epidemiology of ESRD among Tunisian children. METHODS: This retrospective study was conducted in pediatric departments in Charles-Nicolle Hospital, Tunis and Hedi Chaker hospital, Sfax, during a period of 15 years (1st January 1998-31st December 2013). We included children who develop ESRD before the age of 15 years. RESULTS: In total, 166 patients were included. The median duration of follow-up was 48 months. We collected respectively 24 children (14.5%) aged less than 2 years, 24 children (14.5%) aged between 2 and 6 years and 118 children (71%) older than 6 years. The sex ratio was equal to 1.4. The mean incidence was 4.25 cases per million children. The main causes were represented by congenital anomalies of the kidneys and urinary tract (35.5%), hereditary renal disease (31.3%) and glomerular kidney disease (9.6%). All patients were treated in kidney transplant dialysis programs; the main mode of dialysis was represented by peritoneal dialysis, which represented the initial dialysis mode in 81% of cases. The transition to hemodialysis was noted in 43.4% cases. Thirty-eight patients (22.8%) were transplanted. The mortality rate was 27.1%. The leading cause of death was cardiovascular diseases (37.7%) and infections (22.2%). CONCLUSION: The creation of a national registry of kidney disease in Tunisia is necessary for a better knowledge of needs for dialysis and renal transplantation in children. PMID- 26906231 TI - Synthesis of Porous Single-Crystalline Platinum Nanocubes Composed of Nanoparticles. AB - Single-crystalline platinum nanocubes with porous morphology were synthesized for the first time by using ethylene glycol, HCl, and polyvinylpyrrolidone as the reducing agents of H2PtCl6. The morphology and size distribution of the Pt particles formed were studied with a high-resolution transmission electron microscope and selected-area electron diffraction pattern. By controlling the material concentrations and reaction temperature and period, Pt single crystals about 5 nm in size were formed in the first stage of the reduction process that had {100} facets, which were stacked one on top of the other, forming porous nanocubes 20-80 nm in length. The synthesized Pt nanocubes exhibited enhanced catalytic activity for methanol oxidation. PMID- 26906232 TI - Cognition. PMID- 26906233 TI - Acute myelitis by human herpes virus 7 in an HIV-infected patient. AB - BACKGROUND: HHV7 reactivation has been occasionally reported as a cause of encephalitis or myelitis in transplant recipients, but to our knowledge it has never been associated with neurological disease in HIV-infected patients. We report a case of acute myelitis in an HIV-infected patient, with sustained HHV-7 DNA amplification in cerebrospinal fluid (CSF) and a favourable response to foscarnet. CASE REPORT: A 40 year-old man with HIV infection was admitted with asymmetric hypoesthesia in legs and paraparesis. He was receiving treatment with efavirenz, emtricitabine and tenofovir, his CD4 count was 580/mm3 and HIV viral load was undetectable. Magnetic resonance imaging showed a focal central hyperintensity on T2 and STIR sequences, on the torathic spinal cord, with slight enhancement after intravenous gadolinium. All microbiological studies were negative except for HHV-7 DNA amplification in CSF. With a diagnosis of idiopathic transverse myelitis, treatment with high-dose intravenous methylprednisolone was initiated. However, paraparesis continued worsening, and a second CSF obtained 12 days after the first one resulted again in HHV-7 amplification. RESULTS: The patient was treated with a 2 week course of foscarnet, and a rapid neurological improvement was noted. After treatment, PCR for HHV-7 in CSF was negative. Neurological exam was normal one month after treatment initiation. CONCLUSION: HHV-7 reactivation may cause neurological disease in patients with HIV infection. Foscarnet is an effective treatment in HHV-7 associated myelitis. PMID- 26906235 TI - Understanding the Aortic Isthmus Doppler Profile and Its Changes with Gestational Age Using a Lumped Model of the Fetal Circulation. AB - OBJECTIVE: The aortic isthmus (AoI) blood flow has a characteristic shape with a small end-systolic notch observed during the third trimester of pregnancy. However, what causes the appearance of this notch is not fully understood. We used a lumped model of the fetal circulation to study the possible factors causing the end-systolic notch and the changes of AoI flow through gestation. METHODS: A validation of the model was performed by fitting patient-specific data from two normal fetuses. Then, different parametric analyses were performed to evaluate the major determinants of the appearance of the end-systolic notch. The changes in the AoI flow profile through gestation were assessed. RESULTS: Our model allows to simulate the AoI waveform. The delay in the onset of ejection together with the longer ejection duration of the right ventricle are the most relevant factors in the origin of the notch. It appears around 25 weeks of gestation and becomes more pronounced with advancing gestation. DISCUSSION: We demonstrated that the end-systolic notch on the AoI flow occurs mainly as a result of a delayed and longer ejection of the right ventricle. Our findings improve the understanding of hemodynamic changes in the fetal circulation and the interpretation of clinical imaging. PMID- 26906237 TI - Large magnetic anisotropy enhancement in size controlled Ni nanowires electrodeposited into nanoporous alumina templates. AB - A large enhancement of the magnetic anisotropy of Ni nanowires (NWs) embedded in anodic aluminium oxide porous membranes is obtained as a result of an induced magnetoelastic (ME) anisotropy contribution. This unusual large anisotropy enhancement depends on the diameter of the NWs and exceeds the magnetostatic (MS) contribution. As a consequence, it leads to effective magnetic anisotropy energies as large as 1.4 * 10(6) erg cm(-3), which are of the same order of magnitude and comparable to the MS energies of harder magnetic materials like Co NWs. Specifically, from ferromagnetic resonance experiments, the magnetic anisotropy of the NWs has been observed to increase as its diameter is decreased, leading to values that are about four times larger than the corresponding value when only the MS anisotropy is present. Our results are consistent with the recently proposed growth mechanism of Ni NWs that proceeds via a poly-crystalline stage at the bottom followed by a single-crystalline stage with texture [110] parallel to the axis of the NWs. A strong correlation between reducing the diameter of the NWs with the decrease of the length of the poly-crystalline segment and the enhancement of the effective magnetic anisotropy has been shown. Magnetization curves obtained from alternating gradient magnetometry experiments show that the average ME anisotropy results from the competition between the magnetic anisotropies of both crystalline segments of the NWs. Understanding the influence of size and confinement effects on the magnetic properties of nanocomposites is of prime interest for the development of novel and agile devices. PMID- 26906236 TI - Automated Electrophysiological and Pharmacological Evaluation of Human Pluripotent Stem Cell-Derived Cardiomyocytes. AB - Automated planar patch clamp systems are widely used in drug evaluation studies because of their ability to provide accurate, reliable, and reproducible data in a high-throughput manner. Typically, CHO and HEK tumorigenic cell lines overexpressing single ion channels are used since they can be harvested as high density, homogenous, single-cell suspensions. While human pluripotent stem cell derived cardiomyocytes (hPSC-CMs) are physiologically more relevant, these cells are fragile, have complex culture requirements, are inherently heterogeneous, and are expensive to produce, which has restricted their use on automated patch clamp (APC) devices. Here, we used high efficiency differentiation protocols to produce cardiomyocytes from six different hPSC lines for analysis on the Patchliner (Nanion Technologies GmbH) APC platform. We developed a two-step cell preparation protocol that yielded cell catch rates and whole-cell breakthroughs of ~80%, with ~40% of these cells allowing electrical activity to be recorded. The protocol permitted formation of long-lasting (>15 min), high quality seals (>2 GOmega) in both voltage- and current-clamp modes. This enabled density of sodium, calcium, and potassium currents to be evaluated, along with dose-response curves to their respective channel inhibitors, tetrodotoxin, nifedipine, and E-4031. Thus, we show the feasibility of using the Patchliner platform for automated evaluation of the electrophysiology and pharmacology of hPSC-CMs, which will enable considerable increase in throughput for reliable and efficient drug evaluation. PMID- 26906238 TI - Musculoskeletal Complaints in Transverse Upper Limb Reduction Deficiency and Amputation in The Netherlands: Prevalence, Predictors, and Effect on Health. AB - OBJECTIVE: (1) To determine the prevalence of musculoskeletal complaints (MSCs) in individuals with upper limb absence in The Netherlands, (2) to assess the health status of individuals with upper limb absence in general and in relation to the presence of MSCs, and (3) to explore the predictors of development of MSCs and MSC-related disability in this population. DESIGN: Cross-sectional study: national survey. SETTING: Twelve rehabilitation centers and orthopedic workshops. PARTICIPANTS: Individuals (n=263; mean age, 50.7+/-16.7y; 60% men) >=18 years old, with transverse upper limb reduction deficiency (42%) or amputation (58%) at or proximal to the carpal level (response, 45%) and 108 individuals without upper limb reduction deficiency or amputation (n=108; mean age, 50.6+/-15.7y; 65% men) (N=371). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Point and year prevalence of MSCs, MSC-related disability (Pain Disability Index), and general health perception and mental health (RAND-36 subscales). RESULTS: Point and year prevalence of MSCs were almost twice as high in individuals with upper limb absence (57% and 65%, respectively) compared with individuals without upper limb absence (27% and 34%, respectively) and were most often located in the nonaffected limb and upper back/neck. MSCs were associated with decreased general health perception and mental health and higher perceived upper extremity work demands. Prosthesis use was not related to presence of MSCs. Clinically relevant predictors of MSCs were middle age, being divorced/widowed, and lower mental health. Individuals with upper limb absence experienced more MSC-related disability than individuals without upper limb absence. Higher age, more pain, lower general and mental health, and not using a prosthesis were related to higher disability. CONCLUSIONS: Presence of MSCs is a frequent problem in individuals with upper limb absence and is associated with decreased general and mental health. Mental health and physical work demands should be taken into account when assessing such a patient. Clinicians should note that MSC-related disability increases with age. PMID- 26906239 TI - Root Canal Morphology and Configuration of 118 Mandibular First Molars by Means of Micro-Computed Tomography: An Ex Vivo Study. AB - INTRODUCTION: The aim of this study was to investigate the root canal system morphology of the mandibular first molar by means of micro-computed tomography. METHODS: The root canal configuration, foramina, and accessory canals frequency of 118 mandibular first molars were investigated by means of micro-computed tomography and 3-dimensional software imaging. A 4-digit system describes the root canal configuration from the coronal to apical thirds and the main foramina number. RESULTS: The most frequent root canal configurations in mesial root were 2-2-2/2 (31.4%), 2-2-1/1 (15.3%), and 2-2-2/3 (11.9%); another 24 different root canal configurations were observed in this root. A 1-1-1/1 (58.5%), 1-1-1/2 (10.2%), and 16 other root canal configurations were observed in the distal root. The mesiobuccal root canal showed 1-4 foramina in 24.6%, and the mesiolingual showed 1-3 foramina in 28.0%. One connecting canal between the mesial root canals was observed in 30.5% and 2 in 3.4%. The distolingual root canal showed 1-4 foramina in 23.7%, whereas a foramen in the distobuccal root canal was rarely detected (3.4%). The mesiobuccal, mesiolingual, and distolingual root canals showed at least 1 accessory canal (14.3, 10.2, and 4.2%, respectively), but the distobuccal had none. CONCLUSIONS: The root canal configuration of mandibular first molars varies strongly. According to our expectations, both the mesial and distal roots showed a high number of morphologic diversifications. The root canal system of the mesial root showed more root canal configuration variations, connecting and accessory canals than the distal root. PMID- 26906240 TI - Investigation of the Efficacy of Passive Ultrasonic Irrigation Versus Irrigation with Reciprocating Activation: An Environmental Scanning Electron Microscopic Study. AB - INTRODUCTION: The objective of this ex vivo study was to compare the efficacy of passive ultrasonic irrigation (PUI) versus a new activation system using reciprocating motion (EasyClean [EC]; Easy Equipamentos Odontologicos, Belo Horizonte, Brazil) to remove debris from the root canal walls at 6 predetermined apical levels using environmental scanning electron microscopy. METHODS: Mesiobuccal root canals of 10 mandibular molars were prepared with a 30/.05 final instrument. The specimens were embedded in flasks containing heavy body silicone, cleaved longitudinally, and 6 round indentations were made into the apical region of the buccal half at 1-mm intervals. The same specimens were used to prepare a blank control group (no debris), a negative control group (completely covered by debris), and 2 experimental groups: PUI and irrigation with reciprocating activation. Standardized images of the indentations were obtained under environmental scanning electron microscopy and assessed by 2 examiners. The amount of debris was then classified using a 4-category scoring system. The kappa test was applied to determine interexaminer agreement, whereas the Kruskal Wallis, Dunn, and Friedman tests were used to compare scores. RESULTS: The EC group had results statistically similar to those of the blank control group for all 6 root levels examined. The PUI group had results statistically similar to those of the negative control group for the 3 most apical levels and similar to those of the blank control group for the 3 most cervical levels. CONCLUSIONS: Activating the irrigant with a reciprocating system (EC) promoted more effective debris removal from the more apical regions of the root canal when compared with PUI. PMID- 26906241 TI - Pulp Obliteration in a Patient with Sclerodermatous Chronic Graft-versus-Host Disease. AB - Dental pulp calcification is a common finding associated with localized dental trauma, genetic disorders, and systemic inflammatory diseases. Chronic graft versus-host disease (cGVHD) is a frequent complication after allogeneic hematopoietic cell transplantation (allo-HCT) characterized by immune-mediated injury to the skin, mouth, eyes, liver, and other tissues, resulting in significant disability and reduced quality of life. We report a patient with sclerodermatous cGVHD who presented with general pulp calcification in all teeth 5 years after allo-HCT. A review of full mouth dental radiographs obtained just before allo-HCT revealed normal-appearing pulp chambers. Based on prior reports of generalized pulp calcification associated with progressive systemic sclerosis, we hypothesized that the etiology was likely related to the presence of cGVHD with associated vascular and fibrotic tissue changes within the pulp vasculature. Clinicians should consider cGVHD in the differential diagnosis of generalized pulp calcification. PMID- 26906243 TI - Removal of Radioactively Marked Calcium Hydroxide from the Root Canal: Influence of Volume of Irrigation and Activation. AB - INTRODUCTION: The purpose of this study was to evaluate the amount of calcium hydroxide (Ca[OH]2) removed by irrigation with different volumes and activation methods. METHODS: One hundred thirty extracted straight, single-rooted human teeth were instrumented to size 45/.04. One hundred twenty teeth were filled with radioactively marked Ca(OH)2 and a gutta-percha point; 10 teeth with only gutta percha served as a negative control. All specimens were stored in saline solution (7 days at 35 degrees C). After storage, teeth were randomly divided into 12 groups (n = 10). The gutta-percha was taken out, and Ca(OH)2 was removed either by irrigation with different volumes (0 mL, 0.5 mL, 1 mL, 2 mL, 4 mL, or 8 mL) or mechanical activation with a 2- or 4-mL volume using a file (Instr) (FlexMaster size 45/.04; VDW, Munich, Germany), a brush (CanalBrush [CB]; Coltene/Whaledent, Langenau, Germany), or passive ultrasonic irrigation (PUI, smooth wire). Irrigation was performed by alternating 40% citric acid and 3% sodium hypochlorite. Residual Ca(OH)2 was measured by scintillation and expressed as a percentage of the original Ca(OH)2. RESULTS: Increasing the irrigation volume led to a significant decrease (P < .05) of residual Ca(OH)2 (0 mL [98.5%], 0.5 mL [21.7%], 1 mL [16.5%], 2 mL [12.9%], 4 mL [8.7%], 8 mL [5.0%], and negative control [0.0%]). Activation led to less residual Ca(OH)2 (2 mL Instr [12.0%], 2 mL CB [11.7%], 2 mL PUI [9.1%], 4 mL Instr [8.5%], 4 mL CB [7.4%], and 4 mL PUI [6.2%]), with significant differences according to the PUI (P < .05). CONCLUSIONS: No irrigation procedure was able to remove Ca(OH)2 completely. PUI was the most effective activation method. However, irrigation with an 8-mL volume was the most effective. PMID- 26906242 TI - Prostaglandin E2 Stimulates EP2, Adenylate Cyclase, Phospholipase C, and Intracellular Calcium Release to Mediate Cyclic Adenosine Monophosphate Production in Dental Pulp Cells. AB - INTRODUCTION: Prostaglandin E2 (PGE2) plays a crucial role in pulpal inflammation and repair. However, its induction of signal transduction pathways is not clear but is crucial for future control of pulpal inflammation. METHODS: Primary dental pulp cells were exposed to PGE2 and 19R-OH PGE2 (EP2 agonist) or sulprostone (EP1/EP3 agonist) for 5 to 40 minutes. Cellular cyclic adenosine monophosphate (cAMP) levels were measured using the enzyme-linked immunosorbent assay. In some experiments, cells were pretreated with SQ22536 (adenylate cyclase inhibitor), H89 (protein kinase A inhibitor), dorsomorphin (adenosine monophosphate-activated protein kinase inhibitor), U73122 (phospholipase C inhibitor), thapsigargin (inhibitor of intracellular calcium release), W7 (calmodulin antagonist), verapamil (L-type calcium channel blocker), and EGTA (extracellular calcium chelator) for 20 minutes before the addition of PGE2. RESULTS: PGE2 and 19R-OH PGE2 (EP2 agonist) stimulated cAMP production, whereas sulprostone (EP1/EP3 agonist) shows little effect. PGE2-induced cAMP production was attenuated by SQ22536 and U73122 but not H89 and dorsomorphin. Intriguingly, thapsigargin and W7 prevented PGE2-induced cAMP production, but verapamil and EGTA showed little effect. CONCLUSIONS: These results indicate that PGE2-induced cAMP production is associated with EP2 receptor and adenylate cyclase activation. These events are mediated by phospholipase C, intracellular calcium release, and calcium calmodulin signaling. These results are helpful for understanding the role of PGE2 in pulpal inflammation and repair and possible future drug intervention. PMID- 26906244 TI - Exposure to Thyroid-Disrupting Chemicals: A Transatlantic Call for Action. PMID- 26906245 TI - Black Nb2O5 nanorods with improved solar absorption and enhanced photocatalytic activity. AB - Black titania, with greatly improved solar absorption, has demonstrated its effectiveness in photocatalysis and photoelectrochemical cells (PEC), inspiring us to explore the blackening of other wide band-gap oxide materials for enhanced performance. Herein, we report the fabrication of black, reduced Nb2O5 nanorods (r-Nb2O5), with active exposed (001) surfaces, and their enhanced photocatalytic and PEC properties. Black r-Nb2O5 nanorods were obtained via reduction of pristine Nb2O5 by molten aluminum in a two-zone furnace. Unlike the black titania, r-Nb2O5 nanorods are well-crystallized, without a core-shell structure, which makes them outstanding in photocatalytic stability. Substantial Nb(4+) cation and oxygen vacancies (VO) were introduced into r-Nb2O5, resulting in the enhanced absorption in both the visible and near-infrared regions and improved charge separation and transport capability. The advantage of the r-Nb2O5 was also proved by its more efficient photoelectrochemical performance (138 times at 1.23 VRHE) and higher photocatalytic hydrogen-generation activity (13 times) than pristine Nb2O5. These results indicate that black r-Nb2O5 is a promising material for PEC application and photocatalysis. PMID- 26906246 TI - An Investigation of Factors Influencing Nurses' Clinical Decision-Making Skills. AB - This study aims to investigate the influencing factors on nurses' clinical decision-making (CDM) skills. A cross-sectional nonexperimental research design was conducted in the medical, surgical, and emergency departments of two university hospitals, between May and June 2014. We used a quantile regression method to identify the influencing factors across different quantiles of the CDM skills distribution and compared the results with the corresponding ordinary least squares (OLS) estimates. Our findings revealed that nurses were best at the skills of managing oneself. Educational level, experience, and the total structural empowerment had significant positive impacts on nurses' CDM skills, while the nurse-patient relationship, patient care and interaction, formal empowerment, and information empowerment were negatively correlated with nurses' CDM skills. These variables explained no more than 30% of the variance in nurses' CDM skills and mainly explained the lower quantiles of nurses' CDM skills distribution. PMID- 26906247 TI - Adult beetles compensate for poor larval food conditions. AB - Life history traits of herbivores are highly influenced by the quality of their hosts, i.e., the composition of primary and secondary plant metabolites. In holometabolous insects, larvae and adults may face different host plants, which differ in quality. It has been hypothesised that adult fitness is either highest when larval and adult environmental conditions match (environmental matching) or it may be mainly determined by optimal larval conditions (silver spoon effect). Alternatively, the adult stage may be most decisive for the actual fitness, independent of larval food exposure, due to adult compensation ability. To determine the influence of constant versus changing larval and adult host plant experiences on growth performance, fitness and feeding preferences, we carried out a match-mismatch experiment using the mustard leaf beetle, Phaedon cochleariae. Larvae and adults were either constantly reared on watercress (natural host) or cabbage (crop plant) or were switched after metamorphosis to the other host. Growth, reproductive traits and feeding preferences were determined repeatedly over lifetime and host plant quality traits analysed. Differences in the host quality led to differences in the development time and female reproduction. Egg numbers were significantly influenced by the host plant species experienced by the adults. Thus, adults were able to compensate for poor larval conditions. Likewise, the current host experience was most decisive for feeding preferences; in adult beetles a feeding preference was shaped regardless of the larval host plant. Larvae or adults reared on the more nutritious host, cabbage, showed a higher preference for this host. Hence, beetles most likely develop a preference when gaining a direct positive feedback in terms of an improved performance, whereby the current experience matters the most. Highly nutritious crop plants may be, in consequence, all the more exploited by potential pests that may show a high plasticity in reproduction and feeding preferences. PMID- 26906249 TI - Do Lehmann cholesteric droplets subjected to a temperature gradient rotate as rigid bodies? AB - We performed a Fluorescence Recovery After Photobleaching (FRAP) experiment during the Lehmann rotation of cholesteric droplets in thermodynamic coexistence with the isotropic liquid and subjected to a temperature gradient. By creating and tracking bleached spots near the surface of banded droplets (in which the cholesteric helix is perpendicular to the gradient) and concentric circle droplets oriented by an electric field (in which the helix is parallel to the gradient), we found that neither type of droplet rotates as a solid. This result shows that the texture rotation is mainly due to the local director rotation. PMID- 26906248 TI - A novel selective prostaglandin E2 synthesis inhibitor relieves pyrexia and arthritis in Guinea pigs inflammatory models. AB - Prostaglandin E2 (PGE2), one of the terminal products in the cyclooxygenase pathway, plays an important role in various inflammatory responses. To determine whether selective inhibition of PGE2 may relieve these inflammatory symptoms, we synthesized a selective PGE2 synthesis inhibitor, compound A [1-(6-fluoro-5,7 dimethyl-1,3-benzothiazol-2-yl)-N-[(1S,2R)-2-(hydroxymethyl)cyclohexyl]piperidine 4-carboxamide], then investigated the effects on pyrexia, arthritis and inflammatory pain in guinea pigs. In LPS-stimulated guinea pig macrophages, compound A selectively inhibited inducible PGE2 biosynthesis in a dose-dependent manner whereas enhanced the formation of thromboxane B2 (TXB2). Compound A suppressed yeast-evoked PGE2 production selectively and enhanced the production of TXB2 and 6-keto PGF1alphain vivo. In addition, compound A relieved yeast induced pyrexia and also suppressed paw swelling in an adjuvant-induced arthritis model. The effect on gastrointestinal (GI) ulcer formation was also evaluated and compound A showed a lower GI adverse effect than indomethacin. However, compound A failed to relieve yeast-induced thermal hyperalgesia. These results suggest that selective inhibition of PGE2 synthesis may have anti-pyretic and anti inflammatory properties without GI side effect, but lack the analgesic efficacy. PMID- 26906250 TI - Enantioselective cyclopropanation of (Z)-3-substituted-2-(4-pyridyl) acrylonitriles catalyzed by Cinchona ammonium salts. AB - Cyclopropane esters holding two quaternary centres were prepared in high yields, complete diastereoselection and up to 83% ee. The reaction described herein entailed reacting (Z)-3-substituted-2-(4-pyridyl)-acrylonitrile, a reactive class of Michael acceptor, with 2-bromomalonate esters in the presence of Cinchona derived phase-transfer catalysts. The reaction allowed multi-gram preparation of the desired products. PMID- 26906251 TI - A label-free and portable graphene FET aptasensor for children blood lead detection. AB - Lead is a cumulative toxicant, which can induce severe health issues, especially in children's case due to their immature nervous system. While realizing large scale monitoring of children blood lead remains challenging by utilizing traditional methods, it is highly desirable to search for alternative techniques or novel sensing materials. Here we report a label-free and portable aptasensor based on graphene field effect transistor (FET) for effective children blood lead detection. With standard solutions of different Pb(2+) concentrations, we obtained a dose-response curve and a detection limitation below 37.5 ng/L, which is three orders lower than the safe blood lead level (100 MUg/L). The devices also showed excellent selectivity over other metal cations such as, Na(+), K(+), Mg(2+), and Ca(2+), suggesting the capability of working in a complex sample matrix. We further successfully demonstrated the detection of Pb(2+) ions in real blood samples from children by using our aptasensors, and explored their potential applications for quantification. Our results underscore such graphene FET aptasensors for future applications on fast detection of heavy metal ions for health monitoring and disease diagnostics. PMID- 26906252 TI - [The World Health Organization report on ageing and health: A gift for the geriatrics community]. PMID- 26906253 TI - Visualizing quantitative microscopy data: History and challenges. AB - Data visualization is a fundamental aspect of science. In the context of microscopy-based studies, visualization typically involves presentation of the images themselves. However, data visualization is challenging when microscopy experiments entail imaging of millions of cells, and complex cellular phenotypes are quantified in a high-content manner. Most well-established visualization tools are inappropriate for displaying high-content data, which has driven the development of new visualization methodology. In this review, we discuss how data has been visualized in both classical and high-content microscopy studies; as well as the advantages, and disadvantages, of different visualization methods. PMID- 26906255 TI - Correction to Tunable Terahertz Hybrid Metal-Graphene Plasmons. PMID- 26906256 TI - A witness seminar on the history of the Human Gene Mapping Workshops. PMID- 26906258 TI - Recent advances in flow injection analysis. AB - A dynamic development of methodologies of analytical flow injection measurements during four decades since their invention has reinforced the solid position of flow analysis in the arsenal of techniques and instrumentation of contemporary chemical analysis. With the number of published scientific papers exceeding 20,000, and advanced instrumentation available for environmental, food, and pharmaceutical analysis, flow analysis is well established as an extremely vital field of modern flow chemistry, which is developed simultaneously with methods of chemical synthesis carried out under flow conditions. This review work is based on almost 300 original papers published mostly in the last decade, with special emphasis put on presenting novel achievements from the most recent 2-3 years in order to indicate current development trends of this methodology. Besides the evolution of the design of whole measuring systems, and including especially new applications of various detections methods, several aspects of implications of progress in nanotechnology, and miniaturization of measuring systems for application in different field of modern chemical analysis are also discussed. PMID- 26906259 TI - Freezing Transitions of Nanoconfined Coarse-Grained Water Show Subtle Dependence on Confining Environment. AB - The solid-to-liquid phase transition in water nanofilms confined between plates, with varying separations and water-plate interactions ranging from strongly hydrophobic to strongly hydrophilic, was simulated using a coarse-grained monatomic water model (mW) and the generalized replica exchange method (gREM). Extensive gREM simulations combined with the statistical temperature weighted histogram analysis method (ST-WHAM) provide a detailed description of the thermodynamic properties intrinsic to the phase transition, including the transition temperature, isobaric heat capacity, phase change enthalpy, entropy, and their dependence on the interplate distance and the plate-water interaction. The ice structure of water nanofilms was characterized at various conditions using the transverse density profile and the distribution of angles formed by hydrogen-bonded neighboring molecules. Flat bilayer ice was observed to be the dominant solid phase at close interplate distance, while puckered bilayer ice, similar to a slab of ice Ih, is the predominant structure at larger interplates. Stable puckered bilayer ice, previously observed to have a low melting point, is observed to have enhanced stability with high melting temperature when confined between hydrophilic plates. These results demonstrate the strong dependence of phase stability and coexistence in nanoconfined systems on the geometry and physical properties of the confining environment. PMID- 26906260 TI - Erratum. PMID- 26906261 TI - Acupuncture and Equine Rehabilitation. AB - Acupuncture is one of the most common veterinary integrative medicine modalities. Acupuncture can greatly contribute to a rehabilitation protocol by promoting analgesia, tissue healing, and muscle strength. Acupuncture is safe, has minimal detrimental side effects, and is well tolerated by most horses. PMID- 26906262 TI - Introduction to Equine Physical Therapy and Rehabilitation. AB - Physical therapy (physiotherapy, or PT) can be broadly defined as the restoration of movement and function and includes assessment, treatment, and rehabilitation. This review outlines the history, definition, and regulation of PT, followed by the core scientific principles of PT. Because musculoskeletal physiotherapy is the predominant subdiscipline in equine PT, encompassing poor performance, back pain syndromes, other musculoskeletal disorders, and some neuromuscular disorders, the sciences of functional biomechanics, neuromotor control, and the sensorimotor system in the spine, pelvis, and peripheral joints are reviewed. Equine PT also may involve PT assessment and treatment of riders. PMID- 26906263 TI - Calcium phosphate mineralization is widely applied in crustacean mandibles. AB - Crustaceans, like most mineralized invertebrates, adopted calcium carbonate mineralization for bulk skeleton reinforcement. Here, we show that a major part of the crustacean class Malacostraca (which includes lobsters, crayfishes, prawns and shrimps) shifted toward the formation of calcium phosphate as the main mineral at specified locations of the mandibular teeth. In these structures, calcium phosphate is not merely co-precipitated with the bulk calcium carbonate but rather creates specialized structures in which a layer of calcium phosphate, frequently in the form of crystalline fluorapatite, is mounted over a calcareous "jaw". From a functional perspective, the co-existence of carbonate and phosphate mineralization demonstrates a biomineralization system that provides a versatile route to control the physico-chemical properties of skeletal elements. This system enables the deposition of amorphous calcium carbonate, amorphous calcium phosphate, calcite and apatite at various skeletal locations, as well as combinations of these minerals, to form graded composites materials. This study demonstrates the widespread occurrence of the dual mineralization strategy in the Malacostraca, suggesting that in terms of evolution, this feature of phosphatic teeth did not evolve independently in the different groups but rather represents an early common trait. PMID- 26906264 TI - Enhanced efficacy of imipenem-colistin combination therapy against multiple-drug resistant Enterobacter cloacae: in vitro activity and a Galleria mellonella model. AB - BACKGROUND/PURPOSE: To investigate the in vitro and in vivo activity of imipenem colistin combination against multidrug-resistant Enterobacter cloacae infections in order to determine whether it should be explored further. METHODS: The antimicrobial activity of colistin alone and in combination with imipenem was assessed versus an imipenem-susceptible isolate, E. cloacae GN1059, or an imipenem-resistant strain, E. cloacae GN0791, isolated in Anhui, China. The potential synergy of imipenem-colistin was evaluated using a checkerboard assay, as well as static time-kill experiments at 1* and 2* minimum inhibitory concentration (MIC). A simple invertebrate model (Galleria mellonella) was developed to assess the in vivo efficacy of imipenem-colistin in treating E. cloacae infection. RESULTS: In checkerboard assays, synergy (defined as a fractional inhibitory concentration index of <= 0.5) was observed between imipenem and colistin for both isolates tested. In time-kill assays, the combination of imipenem-colistin at 1* or 2* MIC resulted in complete killing of both strains. In the G. mellonella larvae model infected with lethal doses of E. cloacae, the combination therapy led to significantly increased survival of the larvae as compared with imipenem or colistin monotherapy alone (p < 0.05). CONCLUSION: This is the first report demonstrating the efficacy of antimicrobial agents in the G. mellonella larvae model of infections caused by E. cloacae. Our study suggested that imipenem-colistin combination was highly active against E. cloacae both in vitro and in the simple invertebrate model, and provided preliminary in vivo evidence that such combination might be useful therapeutically. PMID- 26906265 TI - Mercury Accumulation, Structural Damages, and Antioxidant and Immune Status Changes in the Gilthead Seabream (Sparus aurata L.) Exposed to Methylmercury. AB - In aquatic systems, mercury (Hg) is an environmental contaminant that causes acute and chronic damage to multiple organs. In fish, practically all of the organic Hg found is in the form of methylmercury (MeHg), which has been associated with animal and human health problems. This study evaluates the impact of waterborne-exposure to sublethal concentrations of MeHg (10 MUg L(-1)) in gilthead seabream (Sparus aurata). Hg was seen to accumulate in liver and muscle, and histopathological damage to skin and liver was detected. Fish exposed to MeHg showed a decreased biological antioxidant potential and increased levels of the reactive oxygen molecules compared with the values found in control fish (nonexposed). Increased liver antioxidant enzyme activities (superoxide dismutase and catalase) were detected in 2 day-exposed fish with respect to the values of control fish. However, fish exposed to MeHg for 10 days showed liver antioxidant enzyme levels similar to those of the control fish but had increased hepato somatic index and histopathological alterations in liver and skin. Serum complement levels were higher in fish exposed to MeHg for 30 days than in control fish. Moreover, head-kidney leukocyte activities increased, although only phagocytosis and peroxidase activities showed a significant increase after 10 and 30 days, respectively. The data show that 30 days of exposure to waterborne MeHg provokes more significant changes in fish than a short-term exposure of 2 or 10 days. PMID- 26906266 TI - The phenotype alterations showed by the res tomato mutant disappear when the plants are grown under semi-arid conditions: Is the res mutant tolerant to multiple stresses? AB - The res (restored cell structure by salinity) mutant, recently identified as the first tomato mutant accumulating jasmonate (JA) without stress, exhibited important morphological alterations when plants were grown under control conditions but these disappeared under salt stress. Since the defense responses against stresses are activated in the res mutant as a consequence of the increased expression of genes from the JA biosynthetic and signaling pathways, the mutant may display a tolerance response not only to salt stress but also to multiple stresses. Here, we show that when res mutant plants are grown under the summer natural conditions of the Mediterranean area, with high temperatures and low relative humidity, the characteristic leaf chlorosis exhibited by the mutant disappears and leaves become dark green over time, with a similar aspect to WT leaves. Moreover, the mutant plants are able to achieve chlorophyll and fluorescence levels similar to those of WT. These results hint that research on res tomato mutant may allow very significant advances in the knowledge of defense responses activated by JA against multiple stresses. PMID- 26906275 TI - Identification of Penicillin G Metabolites under Various Environmental Conditions Using UHPLC-MS/MS. AB - In this work, we investigate the stability of penicillin G in various conditions including acidic, alkaline, natural acidic matrices and after treatment of citrus trees that are infected with citrus greening disease. The identification, confirmation, and quantitation of penicillin G and its various metabolites were evaluated using two UHPLC-MS/MS systems with variable capabilities (i.e., Thermo Q Exactive Orbitrap and Sciex 6500 QTrap). Our data show that under acidic and alkaline conditions, penicillin G at 100 ng/mL degrades quickly, with a determined half-life time of approximately 2 h. Penillic acid, penicilloic acid, and penilloic acid are found to be the most abundant metabolites of penicillin G. These major metabolites, along with isopenillic acid, are found when penicillin G is used for treatment of citrus greening infected trees. The findings of this study will provide insight regarding penicillin G residues in agricultural and biological applications. PMID- 26906276 TI - Effects of Fluoride on the Expression of p38MAPK Signaling Pathway-Related Genes and Proteins in Spleen Lymphocytes of Mice. AB - This study investigated the effects of sodium fluoride on the expression of p38MAPK signaling pathway-related genes and proteins in the spleen lymphocytes of mice, revealing the mechanism of the toxicity of fluoride to the immune system. The spleen lymphocytes, isolated from mice consuming different NaF doses (0, 50, 100, and 150 mg/L) for 60 days, were cultured in medium with bacteria lipopolysaccharide, and the cells' proliferation ability was analyzed through MTT; real-time PCR detected the change of MLK3/MKK6/p38MAPK/MSK1/ATF1 on mRNA, and the difference of protein expression of MKK6/p38MAPK were detected through the Western blotting. The results suggested that the proliferation ability of spleen lymphocytes isolated from mice consuming different NaF doses is lower, and the expression of genes and proteins of MKK6/p38MAPK showed a decreasing trend. These results demonstrate that fluoride can suppress the activation of p38MAPK pathway in mice spleen lymphocytes and further influences the function of the immune system. PMID- 26906277 TI - A review of methods for the signal quality assessment to improve reliability of heart rate and blood pressures derived parameters. AB - The assessment of signal quality has been a research topic since the late 1970s, as it is mainly related to the problem of false alarms in bedside monitors in the intensive care unit (ICU), the incidence of which can be as high as 90 %, leading to alarm fatigue and a drop in the overall level of nurses and clinicians attention. The development of efficient algorithms for the quality control of long diagnostic electrocardiographic (ECG) recordings, both single- and multi lead, and of the arterial blood pressure (ABP) signal is therefore essential for the enhancement of care quality. The ECG signal is often corrupted by noise, which can be within the frequency band of interest and can manifest similar morphologies as the ECG itself. Similarly to ECG, also the ABP signal is often corrupted by non-Gaussian, nonlinear and non-stationary noise and artifacts, especially in ICU recordings. Moreover, the reliability of several important parameters derived from ABP such as systolic blood pressure or pulse pressure is strongly affected by the quality of the ABP waveform. In this work, several up-to date algorithms for the quality scoring of a single- or multi-lead ECG recording, based on time-domain approaches, frequency-domain approaches or a combination of the two will be reviewed, as well as methods for the quality assessment of ABP. Additionally, algorithms exploiting the relationship between ECG and pulsatile signals, such as ABP and photoplethysmographic recordings, for the reduction in the false alarm rate will be presented. Finally, some considerations will be drawn taking into account the large heterogeneity of clinical settings, applications and goals that the reviewed algorithms have to deal with. PMID- 26906278 TI - Neurofeedback training with a motor imagery-based BCI: neurocognitive improvements and EEG changes in the elderly. AB - Neurofeedback training (NFT) has shown to be promising and useful to rehabilitate cognitive functions. Recently, brain-computer interfaces (BCIs) were used to restore brain plasticity by inducing brain activity with an NFT. In our study, we hypothesized that an NFT with a motor imagery-based BCI (MI-BCI) could enhance cognitive functions related to aging effects. To assess the effectiveness of our MI-BCI application, 63 subjects (older than 60 years) were recruited. This novel application was used by 31 subjects (NFT group). Their Luria neuropsychological test scores were compared with the remaining 32 subjects, who did not perform NFT (control group). Electroencephalogram changes measured by relative power (RP) endorsed cognitive potential findings under study: visuospatial, oral language, memory, intellectual and attention functions. Three frequency bands were selected to assess cognitive changes: 12, 18, and 21 Hz (bandwidth 3 Hz). Significant increases (p < 0.01) in the RP of these frequency bands were found. Moreover, results from cognitive tests showed significant improvements (p < 0.01) in four cognitive functions after performing five NFT sessions: visuospatial, oral language, memory, and intellectual. This established evidence in the association between NFT performed by a MI-BCI and enhanced cognitive performance. Therefore, it could be a novel approach to help elderly people. PMID- 26906280 TI - Fluid-structure interaction modeling of calcific aortic valve disease using patient-specific three-dimensional calcification scans. AB - Calcific aortic valve disease (CAVD) is characterized by calcification accumulation and thickening of the aortic valve cusps, leading to stenosis. The importance of fluid flow shear stress in the initiation and regulation of CAVD progression is well known and has been studied recently using fluid-structure interaction (FSI) models. While cusp calcifications are three-dimensional (3D) masses, previously published FSI models have represented them as either stiffened or thickened two-dimensional (2D) cusps. This study investigates the hemodynamic effect of these calcifications employing FSI models using 3D patient-specific calcification masses. A new reverse calcification technique (RCT) is used for modeling different stages of calcification growth based on the spatial distribution of calcification density. The RCT is applied to generate the 3D calcification deposits reconstructed from a patient-specific CT scans. Our results showed that consideration of 3D calcification deposits led to both higher fluid shear stresses and unique fluid shear stress distribution on the aortic side of the cusps that may have an impact on the calcification growth rate. However, the flow did not seem to affect the geometry of the calcification during the growth phase. PMID- 26906279 TI - Calf muscle perfusion as measured with magnetic resonance imaging to assess peripheral arterial disease. AB - We hypothesized that skeletal muscle perfusion is impaired in peripheral arterial disease (PAD) patients compared to healthy controls and that perfusion patterns exhibit marked differences across five leg muscle compartments including the anterior muscle group (AM), lateral muscle group (LM), deep posterior muscle group (DM), soleus (SM), and the gastrocnemius muscle (GM). A total of 40 individuals (26 PAD patients and 14 healthy controls) underwent contrast-enhanced magnetic resonance imaging (CE-MRI) utilizing a reactive hyperemia protocol. Muscle perfusion maps were developed for AM, LM, DM, SM, and GM. Perfusion maps were analyzed over the course of 2 min, starting at local pre-contrast arrival, to study early-to-intermediate gadolinium enhancement. PAD patients had a higher fraction of hypointense voxels at pre-contrast arrival for all five muscle compartments compared with healthy controls (p < 0.0005). Among PAD patients, the fraction of hypointense voxels of the AM, LM, and GM were inversely correlated with the estimated glomerular filtration rate (eGFR; r = -0.509, p = 0.008; r = 0.441, p = 0.024; and r = -0.431, p = 0.028, respectively). CE-MRI-based skeletal leg muscle perfusion is markedly reduced in PAD patients compared with healthy controls and shows heterogeneous patterns across calf muscle compartments. PMID- 26906281 TI - Responses of infrared-sensitive tectal units of the pit viper Crotalus atrox to moving objects. AB - Rattlesnakes perceive IR radiation with their pit organs. This enables them to detect and strike towards warm-blooded prey even in the dark. In addition, the IR sense allows rattlesnakes to find places for thermoregulation. Animate objects (e.g., prey) tend to move and thus cause moving IR images across the pit membrane. Even when an object is stationary, scanning head movements of rattlesnakes will result in moving IR images across the pit membrane. We recorded the neuronal activity of IR-sensitive tectal neurons of the rattlesnake Crotalus atrox while stimulating the snakes with an IR source that moved horizontally at various velocities. As long as object velocity was low (angular velocity of ~5 degrees /s) IR-sensitive tectal neurons hardly showed any responses. With increasing object velocity though, neuronal activity reached a maximum at ~50 degrees /s. A further increase in object velocity up to ~120 degrees /s resulted in a slight decrease of neuronal activity. Our results demonstrate the importance of moving stimuli for the snake's IR detection abilities: in contrast to fast moving objects, stationary or slowly moving objects will not be detected when the snake is motionless, but might be detected by scanning head movements. PMID- 26906267 TI - Oxidant Mechanisms in Renal Injury and Disease. AB - SIGNIFICANCE: A common link between all forms of acute and chronic kidney injuries, regardless of species, is enhanced generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) during injury/disease progression. While low levels of ROS and RNS are required for prosurvival signaling, cell proliferation and growth, and vasoreactivity regulation, an imbalance of ROS and RNS generation and elimination leads to inflammation, cell death, tissue damage, and disease/injury progression. RECENT ADVANCES: Many aspects of renal oxidative stress still require investigation, including clarification of the mechanisms which prompt ROS/RNS generation and subsequent renal damage. However, we currently have a basic understanding of the major features of oxidative stress pathology and its link to kidney injury/disease, which this review summarizes. CRITICAL ISSUES: The review summarizes the critical sources of oxidative stress in the kidney during injury/disease, including generation of ROS and RNS from mitochondria, NADPH oxidase, and inducible nitric oxide synthase. The review next summarizes the renal antioxidant systems that protect against oxidative stress, including superoxide dismutase and catalase, the glutathione and thioredoxin systems, and others. Next, we describe how oxidative stress affects kidney function and promotes damage in every nephron segment, including the renal vessels, glomeruli, and tubules. FUTURE DIRECTIONS: Despite the limited success associated with the application of antioxidants for treatment of kidney injury/disease thus far, preventing the generation and accumulation of ROS and RNS provides an ideal target for potential therapeutic treatments. The review discusses the shortcomings of antioxidant treatments previously used and the potential promise of new ones. Antioxid. Redox Signal. 25, 119-146. PMID- 26906282 TI - Persistent Atrial Fibrillation Ablation using the Tip-Versatile Ablation Catheter. AB - BACKGROUND: The mechanisms by which persistent atrial fibrillation (PsAF) develops are incompletely understood. Consequently, the optimal strategy for the ablative management of PsAF remains debated. Current methods are often time consuming, complex and non-reproducible. We assessed the Tip-Versatile Ablation Catheter (T-VAC) technique, a rapidly delivered, empirical technique based on the box-set concept using duty-cycled linear catheter ablation technology. METHODS: Forty-four procedures in 40 patients undergoing PsAF ablation with the novel technique were prospectively entered onto a database: 27 de novo. Primary endpoint was freedom from arrhythmia at over two-year follow-up. Secondary endpoints were time to first arrhythmia recurrence, freedom from atrial fibrillation (AF) on and off antiarrhythmic drugs (AAD), procedural and fluoroscopy duration and complication rate. RESULTS: At mean follow-up of 33 months, absolute freedom from arrhythmia recurrence was 45% in the de novo group. Overall, at 33 (IQR 24-63) months, 60% of de novo patients were in sustained normal sinus rhythm and a further 15% reported only occasional paroxysms of AF at long-term follow-up. Procedure time was 192+/-25 mins, total energy delivered 2239+/-883s and fluoroscopy time was 60+/-10mins. CONCLUSION: In selected patients with persistent AF, a long-term rate of 60% arrhythmia free survival off AAD can be achieved using this novel T-VAC technique. PMID- 26906283 TI - Impact of New-generation Hybrid Imaging Technology on Radiation Dose during Percutaneous Coronary Interventions and Trans-femoral Aortic Valve Implantations: A comparison with conventional flat-plate angiography. AB - BACKGROUND: Technological advancements in newer-generation catheterisation laboratories may reduce patient and occupational radiation exposure. METHODS: We compared fluoroscopy time and dose-area product (DAP) between a Philips Allura X PER FD20 and Siemens Artis Zeego Hybrid systems for 47 single-vessel percutaneous coronary interventions (PCI) and 35 transcatheter aortic valve implantations (21 Corevalve, 14 Edwards Sapien TAVI) using the FD20, versus 30 PCI and 28 TAVI (15 Corevalve, 13 Sapien) with the Zeego over a 24-month period. RESULTS: Multivariate analysis revealed that, adjusting for patient weight and fluoroscopy time, DAP (median, interquartile range) was 26% lower for PCI with the Zeego than the FD20 [55.6 (27.0-91.5) vs 77.6 (51.2-129.1) Gy.cm(2), P=0.03)] and using tomographic imaging with the Zeego did not increase DAP for TAVI procedures [98.1 (65.9-136.6) vs 112.4 (64.9-156.2) Gy.cm(2) (P=NS). Although fluoroscopy times were longer for TAVI procedures than PCI with both systems (23.5-24.4 vs 7.3 9.2mins, p<0.0001), there was a significant difference in DAP between PCI and combined TAVI with the Zeego (55.6 vs 112.4Gy.cm(2), P<0.006) but not with the FD20 (77.6 vs 98.1Gy.cm(2), P=NS). CONCLUSION: Specific dose-reducing features of the new-generation system reduced DAP more for PCI than TAVI, as valve replacement procedures use additional cine-acquisition not necessary for PCI. PMID- 26906284 TI - Chronic Total Occlusion - Percutaneous Coronary Intervention (CTO-PCI) Experience in a Single, Multi-operator Australian Centre: Need for dedicated CTO-PCI programs. AB - BACKGROUND: Chronic total occlusions (CTOs) represent a unique set of lesions for percutaneous coronary intervention (PCI) because of the complexity of techniques required to treat them. METHODS: We retrospectively reviewed the CTO-PCI experience between January 2010 and December 2012, in a multi-operator single centre, which is one of the largest volume PCI centres in Australia. RESULTS: Eighty-two patients (62.6+/-11.3 years, 85% males) who had CTO-PCIs were included. The most common site of CTO was the right coronary artery (44%), followed by the left circumflex (30%) and left anterior descending (26%) arteries. Using the Japanese CTO scoring system, 34% of lesions were classified as easy, 37% intermediate, 23% difficult and 6% very difficult. All PCIs were performed by antegrade approach. Selected procedural characteristics included: re attempt procedure 10%; multiple access sites 21%; more than one guidewire 77%; additional support modality 60%; drug-eluting stents 97%; stent number 1.6+/-0.8; total stent length 40.1+/-24.5mm; fluoroscopy time 33+/-17min; contrast volume 257.2+/-110.8mL. Overall CTO success rate was 60%. In-hospital adverse outcomes included 1.2% mortality, 9.8% peri-procedural myocardial infarction, 4.9% emergency bypass surgery, 3% cardiac tamponade and 4.9% contrast induced nephropathy. CONCLUSION: We report modest success rates in a single Australian centre experience in a relatively conservative cohort of CTO-PCI prior to the initiation of a dedicated CTO revascularisation program. PMID- 26906285 TI - Increased Intraregional Synchronized Neural Activity in Adult Brain After Prolonged Adaptation to High-Altitude Hypoxia: A Resting-State fMRI Study. AB - The human brain is intrinsically plastic such that its functional architecture can be reorganized in response to environmental pressures and physiological changes. However, it remains unclear whether a compensatory modification of spontaneous neural activity occurs in adult brain during prolonged high-altitude (HA) adaptation. In this study, we obtained resting-state functional magnetic resonance (MR) images in 16 adults who have immigrated to Qinghai-Tibet Plateau (2300-4400 m) for 2 years and in 16 age-matched sea level (SL) controls. A validated regional homogeneity (Reho) method was employed to investigate the local synchronization of resting-state functional magnetic resonance imaging (fMRI) signals. Seed connectivity analysis was carried out subsequently. Cognitive and physiological assessments were made and correlated with the image metrics. Compared with SL controls, global mean Reho was significantly increased in HA immigrants as well as a regional increase in the right inferolateral sensorimotor cortex. Furthermore, mean z-Reho value extracted within the inferolateral sensorimotor area showed trend-level significant inverse correlation with memory search reaction time in HA immigrants. These observations, for the first time, provide evidence of adult brain resilience of spontaneous neural activity after long-term HA exposure without inherited and developmental effects. Resting-state fMRI could yield valuable information for central mechanisms underlying respiratory and cognitive compensations in adults during prolonged environmentally hypoxic adaptation, paving the way for future HA adaptive training. PMID- 26906286 TI - Lycopodium clavatum exine microcapsules enable safe oral delivery of 3,4 diaminopyridine for treatment of botulinum neurotoxin A intoxication. AB - 3,4-Diaminopyridine has shown promise in reversing botulinum intoxication, but poor pharmacokinetics and a narrow therapeutic window limit its clinical utility. Thus, we developed a pH-dependent oral delivery platform using club moss spore exines. These exine microcapsules slowed 3,4-diaminopyridine absorption, limited its seizure activity, and enabled delivery of doses which prolonged mouse survival after botulism neurotoxin A intoxication. PMID- 26906287 TI - Consensus document for the diagnosis and treatment of idiopathic pulmonary fibrosis: Joint Consensus of Sociedade Portuguesa de Pneumologia, Sociedade Portuguesa de Radiologia e Medicina Nuclear e Sociedade Portuguesa de Anatomia Patologica. AB - Idiopathic pulmonary fibrosis is a rare interstitial lung disease included in the Idiopathic Interstitial Pneumonias group. Although several potential risk factors have been described, it is a progressive fibrosing disease of unknown cause affecting mainly adults over 50 years and associated with a poor prognosis, reflected in a median survival of 2-3 years after diagnosis. The concept of a multidisciplinary working group for the diagnosis of idiopathic pulmonary fibrosis is based on the need to have experienced pulmonologists, radiologists and pathologists in the evaluation and correct treatment of the disease, and requires the use of all available data about individual patients, standardized (largely through High Resolution Computed Tomography and pathology when needed) as well as non-standardized data (laboratory, serology and biomarkers). This approach helps to increase diagnostic accuracy and is an internationally accepted recommendation. In regard to therapy, the situation has changed radically since the publication of the ATS/ERS/JRS/ALAT 2011 guidelines on the diagnosis and management of idiopathic pulmonary fibrosis where it was stressed that no proven therapy exists for this disease. Currently besides non-pharmacological treatment, therapy of complications and comorbidities and palliative care, nintedanib and pirfenidone, two compounds with pleiotropic mechanisms of action, are to date, the two drugs with confirmed efficacy in slowing functional decline and disease progression in idiopathic pulmonary fibrosis patients. PMID- 26906288 TI - Prevalence of secondhand smoke exposure in asthmatic children at home and in the car: A cross-sectional study. AB - OBJECTIVE: To compare secondhand smoke exposure (SHSe) prevalence at home and inside the car between asthmatic and non-asthmatic Portuguese children. MATERIALS AND METHODS: This is a cross-sectional study that assessed children's SHSe in a representative sample of nine Portuguese cities. A validated self-reported questionnaire was administered to a random sample of 4th grade students during the school year of 2010/2011. The asthma prevalence was defined by the answers to three questions regarding asthma symptoms, medication and inhaler use. We performed chi-square tests and analysed frequencies, contingency tables, confidence intervals, and odd-ratios. RESULTS: The self-reported questionnaire was administered to 3187 students. Asthma prevalence was 14.8% (472 students). Results showed that 32.3% of non-asthmatic children and 32.4% of asthmatic children were exposed to secondhand smoke as at least one of their household members smoked at home. The prevalence of parental smoking, smoking among fathers and smoking among mothers at home was also similar in both groups (asthmatic and non-asthmatic children). SHSe inside the car was 18.6% among non-asthmatic children and 17.9% among asthmatic children. CONCLUSIONS: Asthmatic and non asthmatic children were equally exposed to secondhand smoke, because no significant differences were found between the two groups concerning the prevalence of SHSe at home and inside the car. These findings highlight the need to include SHSe brief advice in paediatric asthma management. PMID- 26906289 TI - First evidence of European eels exiting the Mediterranean Sea during their spawning migration. AB - The migration route and the spawning site of the European eel Anguilla anguilla are still uncertain. It has been suggested that the Mediterranean eel stock does not contribute to spawning because there is no evidence of eels leaving the Mediterranean Sea. To test this hypothesis, we equipped eight female silver eels from the south of France with pop-up satellite tags during escapement from coastal waters. Once in deeper water, the eels quickly established diel vertical migration (DVM) between the upper and lower mesopelagic zone. Five tagged eels were taken by predators within the Mediterranean, but two eels reached the Atlantic Ocean after six months and at distances greater than 2000 km from release. These eels ceased their DVM while they negotiated the Gibraltar Strait, and remained in deep water until they reached the Atlantic Ocean, when they recommenced DVM. Our results are the first to show that eels from Mediterranean can cross the Strait of Gibraltar and continue their migration into the Atlantic Ocean. This finding suggests that Mediterranean countries, as for other EU states, have an important role to play in contributing to conservation efforts for the recovery of the European eel stock. PMID- 26906290 TI - Thermoresponsive Epitope Surface-Imprinted Nanoparticles for Specific Capture and Release of Target Protein from Human Plasma. AB - Among various artificial antibodies, epitope imprinted polymer has been paid increasingly attention. To modulate the "adsorption and release" behavior by environment stimuli, N-isopropylacrylamide, was adopted to fabricate the thermoresponsive epitope imprinted sites. The prepared imprinted materials could adsorb 46.6 mg/g of target protein with the imprinting factor of 4.0. The template utilization efficiency could reach as high as 8.21%. More importantly, in the real sample, the materials could controllably capture the target protein from the human plasma at 45 degrees C and release it at 4 degrees C, which demonstrated the "on-demand" application potentials of such materials in the biomolecule recognition field. PMID- 26906292 TI - Inhibition of HL-60 cell growth via cell cycle arrest and apoptosis induction by a cycloartane-labdane heterodimer from Pseudolarix amabilis. AB - Pseudolaridimer C (), a rarely encountered cycloartane-labdane Diels-Alder adduct was isolated from the cones of Pseudolarix amabilis. The structure and absolute configuration of were established by comprehensive NMR and CD spectral analysis. The WST-8 assay indicated that time and dose dependently inhibited the proliferation of human leukemia cells HL-60 at 1-10 MUM. DAPI and Annexin V FITC/PI double staining method, and DNA ladder experiments all proved that had significant dose-dependent effects on HL-60 cell apoptosis. A further mechanism study indicated that the apoptosis was associated with the cell cycle arrest during the G2/M phase, and the activation of caspase-9, -3, -7, and poly-(ADP ribose)-polymerase (PARP). PMID- 26906293 TI - Influence of endogenous glucagon-like peptide-2 on lipid disorders in mice fed a high-fat diet. AB - AIM: The purpose of the present study was to investigate the influence of endogenous glucagon-like peptide-2 (GLP-2) on lipid profile in mice fed a standard diet (STD) or a high-fat diet (HFD). MATERIALS AND METHODS: HFD- and age matched STD mice were injected once a day with GLP-2 (3-33), a GLP-2 receptor (GLP-2R) antagonist, or vehicle for 4 weeks. RESULTS: HFD mice displayed increased intrahepatic lipid concentration and hepatic steatosis and higher plasma concentrations of cholesterol, LDL, AST, and ALT than STD mice. No difference was observed in lipid fecal elimination. In STD mice, the chronic treatment with GLP-2 (3-33) did not affect any parameter, while in HFD mice, it enhanced plasma triglycerides, cholesterol, ALT, and AST and reduced HDL, it increased intrahepatic lipid concentration, and it worsened the hepatic steatosis degree, without affecting lipid fecal elimination. CONCLUSIONS: The present results suggest that GLP-2R antagonism worsens lipid disorders in HFD mice, and endogenous GLP-2 might even exert a defensive role against lipid imbalance. PMID- 26906295 TI - Clinical and Prognostic Factors Associated With Survival in Mexican Patients With Idiopathic Inflammatory Myopathies. AB - BACKGROUND: Factors associated with survival in patients with idiopathic inflammatory myopathies are heterogeneous. OBJECTIVE: This study aimed to describe clinical and prognostic factors associated with survival in Mexican patients with idiopathic inflammatory myopathies. METHODS: Patients with dermatomyositis (DM) and polymyositis (PM) seen at a tertiary care center from 1985 to 2012 were included. Demographic and clinical characteristics, comorbidities, treatment, and the time to death were recorded. Patients with juvenile DM were excluded. Univariate and multivariate analyses were performed to identify factors associated with mortality. RESULTS: A total of 264 patients with DM and 69 patients with PM were studied. Patients with DM had lower levels of creatine phosphokinase, less cumulative dose of prednisone, higher frequency of dysphagia, and no difference in frequency of interstitial lung disease compared with patients with PM. Patients with DM had lower survival during the first 4 years of disease (80%; 95% confidence interval [CI], 0.74-0.85 vs 89%; 95% CI, 0.78-0.95; P = 0.03 log-rank). Respiratory failure due to pulmonary infection was the main cause of death in patients with DM; miscellaneous causes were responsible for death in patients with PM. Muscular strength (hazard ratio [HR], 0.48; 95% CI, 0.27-0.83; P = 0.01), platelet count (HR, 0.98; 95% CI, 0.98-0.99; P = 0.002), as well as ever use of methotrexate (HR, 0.21; 95% CI, 0.07-0.65; P = 0.007) and azathioprine (HR, 0.21; 95% CI, 0.06-0.68; P = 0.009) were independent factors associated with mortality in patients with DM; in those with PM, only cancer was associated (HR, 8.0; 95% CI, 1.4-43.9; P = 0.01). CONCLUSIONS: Patients with DM had lower survival during the first 4 years of disease than patients with PM. Factors associated with mortality differed in both groups. PMID- 26906294 TI - Subnanometre enzyme mechanics probed by single-molecule force spectroscopy. AB - Enzymes are molecular machines that bind substrates specifically, provide an adequate chemical environment for catalysis and exchange products rapidly, to ensure fast turnover rates. Direct information about the energetics that drive conformational changes is difficult to obtain. We used subnanometre single molecule force spectroscopy to study the energetic drive of substrate-dependent lid closing in the enzyme adenylate kinase. Here we show that in the presence of the bisubstrate inhibitor diadenosine pentaphosphate (AP5A), closing and opening of both lids is cooperative and tightly coupled to inhibitor binding. Surprisingly, binding of the substrates ADP and ATP exhibits a much smaller energetic drive towards the fully closed state. Instead, we observe a new dominant energetic minimum with both lids half closed. Our results, combining experiment and molecular dynamics simulations, give detailed mechanical insights into how an enzyme can cope with the seemingly contradictory requirements of rapid substrate exchange and tight closing, to ensure efficient catalysis. PMID- 26906296 TI - Assessment of American College of Rheumatology-Endorsed Quality Indicators in Rheumatoid Arthritis Patients: A Quality Improvement Initiative. AB - BACKGROUND: The American College of Rheumatology endorses 7 rheumatoid arthritis (RA) quality indicators (QIs), which we used to access quality of care at our institution. OBJECTIVE: The aim of this study was to assess the quality of care provided to RA patients at our outpatient rheumatology practice based on adherence to 7 QIs. METHODS: We performed a retrospective paper chart review and included 356 RA patients to determine adherence to each QI. A chi test analyzed trends in the assessment of disease activity and functional status. RESULTS: There was excellent adherence to disease-modifying antirheumatic drug therapy (99.4%) and managing worsening disease (100%). Assessment of disease activity and functional status increased over the study period (72.8% to 94.2% and 70.8% to 93.4%, respectively). Despite this, none of our patients had disease prognosis classified and documented. Tuberculosis screening was done in 87.9%. Only a small percentage (1.4%) of patients met criteria for a glucocorticoid management plan, thus limiting our assessment of this QI. CONCLUSIONS: Excellent adherence to disease-modifying antirheumatic drug therapy and management is likely due to targeting clinical remission. Assessment of disease activity and functional status not only rose each year, but also is higher compared with similar studies. This may be due to an increased awareness of QIs and the utility of objective measures of disease activity. Deficient documentation of prognosis may be due to a lack of awareness of its importance. Suboptimal tuberculosis screening may be an artifact of poor documentation. We propose interventions to improve adherence. PMID- 26906297 TI - Synovial Fluid Findings and Demographic Analysis of Patients With Coexistent Intra-articular Monosodium Urate and Calcium Pyrophosphate Crystals. AB - OBJECTIVES: The aim of this study was to investigate the characteristics of arthritis in which monosodium urate (urate) and calcium pyrophosphate (CPP) crystals coexisted in synovial fluid (SF) to aid patient management and set a baseline from which to investigate the pathophysiological basis of an unusual coexistence of 2 disorders. METHODS: Synovial fluid analyses of 33,000 patients were reviewed, identifying those containing urate and/or CPP crystals. Synovial fluid cell count and differential cell count, together with patient age and gender, were retrieved from a computerized database spanning 22 years of SF analysis. RESULTS: In 6983 consecutive SF samples containing crystals, CPP crystals were found in 3685 (53%), urate in 3127 (44.5%), and both in 171 (2.5%). These 171 cases were deemed to have a mixed crystal arthropathy (MCA). Patients with MCA were 77% male and 23% female, and the highest incidence was found in those aged 76 to 80 years.Most commonly (69.4% of cases of MCA), high numbers (>20/10 high-power field) of both crystals and an acute inflammatory cell count were found. In the remainder, other patterns of crystals and cells were observed, perhaps suggesting different clinical situations in which these crystals coexist. CONCLUSIONS: This study presents evidence showing that with careful microscopic analysis the coexistence of urate and CPP crystals in a single joint is found in 2.5% of cases of crystal arthritis. The different patterns of SF findings and patient demography described here are novel and might have implications for patient management. PMID- 26906298 TI - Bone Mineral Density in Patients With Rheumatoid Arthritis and 4-Year Follow-up Results. AB - BACKGROUND: Osteoporosis is a common complication in patients with rheumatoid arthritis (RA). The change of bone mineral density (BMD) in patients with RA is slow, and little data are known about the long-term change of BMD. OBJECTIVES: This study aimed to determine the frequency of osteoporosis and the long-term change on BMD in a cohort of Chinese patients with RA routinely receiving calcium and vitamin D supplementation. METHODS: A total of 304 consecutive patients with RA were recruited. Bone mineral density measurements of the forearm, lumbar spine, and total hip were performed by dual-energy x-ray absorptiometry and compared with 200 age- and sex-matched healthy controls. Risk factors were analyzed by logistic regression models. RESULTS: The prevalence of osteoporosis at all measured sites in patients with RA was statistically significantly higher than in healthy controls. A total of 107 patients of the cohort had a mean of 4 years of follow-up. More patients with BMD decrease were found without calcium and vitamin D use compared with those who continuously took calcium and vitamin D (64.3% vs 19.8% at the forearm and 28.6% vs 16.1% at the total hip, respectively). Only the use of calcium and vitamin D supplementation was associated with a decreased risk of BMD decrease both at the forearm and at the total hip. CONCLUSIONS: Osteoporosis is common in Chinese patients with RA. Routine use of calcium and vitamin D supplementation decreased the risk of BMD decrease and should be recommended for all patients with RA. PMID- 26906299 TI - Use of Glucuronidated Mycophenolic Acid Levels for Therapeutic Monitoring in Pediatric Lupus Nephritis Patients. AB - BACKGROUND/OBJECTIVES: Mycophenolate mofetil (MMF) is used to treat pediatric onset lupus nephritis (pLN). Data are equivocal on the use of plasma mycophenolic acid (MPA) levels as a measure of efficacy and predictor of therapeutic outcomes in pLN. Glucuronidated MPA (MPA-G) is an inactive metabolite that is a marker of adequate absorption and normal metabolism of MMF. We evaluated the use of MPA and MPA-G levels in routine care of pLN. METHODS: This was a retrospective study of pLN patients treated with MMF dosed at 600 mg/m. Clinical renal remission (CR) was defined as proteinuria of less than 500 mg/24 h. Midinterval MPA and MPA-G plasma levels were drawn during routine follow-up, approximately 6 hours after the previous dose of MMF. Steady-state levels of MPA were calculated using pharmacokinetics and compared with routine midinterval plasma MPA levels. RESULTS: Seventeen pLN patients treated with MMF had MPA and MPA-G levels. Eleven patients were in CR; 6 were not in CR at the time of evaluation and had not responded to MMF after more than 3 months of therapy. The mean MPA level for patients in CR was 3.26 +/- 2.02 MUg/mL compared with 3.02 +/- 1.76 MUg/mL for patients not in CR. Three patients in CR did not have detectable levels of MPA. Calculated steady-state levels of MPA did not reflect the observed levels. Glucuronidated MPA levels were therapeutic (44.2 +/- 26.7 MUg/mL) in patients in CR, but low (29.88 +/- 22 MUg/mL) in patients not in CR (not statistically significant). CONCLUSIONS: Midinterval plasma levels of MPA do not reflect predicted steady-state levels in pLN and do not correlate with clinical response. Midinterval plasma levels of MPA-G indicate adequate absorption and may correlate better with clinical pLN activity. PMID- 26906300 TI - Familial Henoch-Schonlein Syndrome. AB - Little attention has been so far paid to familial cases of Henoch-Schonlein syndrome. We performed a search of the Medical Subject Headings terms (Henoch or Schonlein OR anaphylactoid purpura OR IgA nephropathy OR Berger nephropathy) AND (family OR familial). We identified no more than 19 reports including 47 families with a total of 100 affected cases: their ages ranged from 1.3 to 51 years (median, 11 years), with a male-to-female ratio of 1.4. Familial cases developed simultaneously in 45% and nonsimultaneously in 55% of the families. Age, male-to female ratio, and clinical findings were not statistically different in cases with simultaneous and nonsimultaneous familial occurrence of Henoch-Schonlein syndrome. Henoch-Schonlein syndrome occurs almost always sporadically. Age at presentation, male-to-female ratio, and findings are similar in familial (both simultaneously and nonsimultaneously occurring) and sporadic Henoch-Schonlein cases. PMID- 26906301 TI - Terminal Ileitis as a Feature of Henoch-Schonlein Purpura Masquerading as Crohn Disease in Adults. AB - Henoch-Schonlein purpura (HSP), more recently termed immunoglobulin A (IgA) vasculitis, is a systemic small-vessel vasculitis characterized by perivascular IgA deposition. This disease manifests clinically as palpable purpura, arthralgia, gastrointestinal symptoms, and renal dysfunction. Although ileitis can be seen in HSP, terminal ileitis is virtually pathognomonic for Crohn disease. We present a comprehensive review of the literature on this association, including 2 cases of our own, to demonstrate the importance of considering HSP in the differential diagnosis of ileitis suggestive of Crohn disease. We review the growing body of literature suggesting a pathophysiologic link between the conditions, possibly through an IgA-mediated mechanism. PMID- 26906302 TI - Complete Remission of Nephrotic Syndrome Without Resolution of Amyloid Deposit After Anti-Tumor Necrosis Factor alpha Therapy in a Patient With Ankylosing Spondylitis. AB - In secondary amyloid A amyloidosis resulting from rheumatologic diseases, tumor necrosis factor alpha blockers have been reported to be effective in the treatment of both arthritis and amyloidosis. However, there have been few reports concerning the alterations of renal tissue histology before and after long-term tumor necrosis factor alpha blockers therapy in secondary renal amyloidosis. We report the histological change after tumor necrosis factor alpha blocker therapy in patient with amyloid A amyloidosis and nephrotic syndrome secondary to underlying ankylosing spondylitis. The patient achieved complete remission of nephrotic syndrome after 17 months of etanercept treatment. We performed the second kidney biopsy after 40 months, and there was little change in the degree of amyloid deposition in the mesangial area and capillary loops compared with the first biopsy. The interstitial inflammation and foot process effacement, however, were fully recovered. PMID- 26906303 TI - Is Bariatric Surgery a Trigger Factor for Systemic Autoimmune Diseases? AB - Bariatric procedures are an effective option for weight loss and control of comorbidities in obese patients. Obesity is a proinflammatory condition in which some cytokines such as leptin, a proinflammatory protein, is elevated and adiponectin, an anti-inflammatory protein, is decreased. In patients undergoing weight reduction surgeries, these hormone levels behave paradoxically. It is not known whether bariatric surgery protects against development of autoinflammatory or autoimmune conditions; nevertheless, changes occurring in the immune system are incompletely understood. In this case series, we describe 4 patients undergoing bariatric surgery, who subsequently developed systemic autoimmune diseases. Patients in our case series were asymptomatic before surgery and developed an autoimmune disease within 11.2 months. Two women fulfilled criteria for systemic lupus erythematosus (one associated with antiphospholipid syndrome), and 2 men developed rheumatoid arthritis. A causal relationship is difficult to establish because factors that could trigger these diseases are multiple, including genetic susceptibility, time elapsed until achievement of ideal weight, and vitamin deficiencies, among others. However, clinicians must be attentive to this possible association. PMID- 26906304 TI - Cerebrotendinous Xanthomatosis: A Treatable Genetic Disease Not to Be Missed. PMID- 26906305 TI - Air Bubbles in the Knee Joint. PMID- 26906308 TI - Erdheim-Chester Histiocytosis Presenting as Ankle Disease. PMID- 26906307 TI - Hemolytic Anemia Induced by Pegloticase Infusion in a Patient With G6PD Deficiency. PMID- 26906309 TI - Spondyloarthropathy-Like Findings and Diffuse Osteosclerosis as the Presenting Feature of Pseudohypoparathyroidism. PMID- 26906310 TI - Sarcoid Fasciitis With Magnetic Resonance Imaging Fascial Enhancement. PMID- 26906311 TI - Endoscopy again supports Colorectal Cancer Awareness Month. PMID- 26906312 TI - Adenomatous polyps in ulcerative colitis and colonic Crohn's disease: less frequent, but does this change surveillance strategy? PMID- 26906313 TI - Temporal trends and variability of colonoscopy performance in gastroenterology practice. PMID- 26906314 TI - Nature of sedation and post-ERCP pancreatitis: is it a question of sedation "not being in my department"? PMID- 26906315 TI - Reply to Thomson. PMID- 26906318 TI - [French comment on article: Rarity of adenomatous polyps in ulcerative colitis and its implications for colonic carcinogenesis]. PMID- 26906319 TI - [French comment on article: Comparison between different colon cleansing products for screening colonoscopy. A noninferiority trial in population-based screening programs in Italy]. PMID- 26906320 TI - [French comment on article: Endoscopist characteristics that influence the quality of colonoscopy]. PMID- 26906321 TI - [French comment on article: Temporal trends and variability of colonoscopy performance in a gastroenterology practice]. PMID- 26906322 TI - [French comment on article: Monitoring colonoscopy withdrawal time significantly improves the adenoma detection rate and the performance of endoscopists]. PMID- 26906323 TI - [French comment on article: Frequency of and risk factors for the surgical resection of nonmalignant colorectal polyps: a population-based study]. PMID- 26906324 TI - Video Comment on Ghanouni et al. PMID- 26906325 TI - Video Comment on le Clercq et al. PMID- 26906326 TI - Video Comment on Tsiamoulos et al. PMID- 26906327 TI - Time related variations in stem cell harvesting of umbilical cord blood. AB - Umbilical cord blood (UCB) contains hematopoietic stem cells and multipotent mesenchymal cells useful for treatment in malignant/nonmalignant hematologic immunologic diseases and regenerative medicine. Transplantation outcome is correlated with cord blood volume (CBV), number of total nucleated cells (TNC), CD34+ progenitor cells and colony forming units in UCB donations. Several studies have addressed the role of maternal/neonatal factors associated with the hematopoietic reconstruction potential of UCB, including: gestational age, maternal parity, newborn sex and birth weight, placental weight, labor duration and mode of delivery. Few data exist regarding as to how time influences UCB collection and banking patterns. We retrospectively analyzed 17.936 cord blood donations collected from 1999 to 2011 from Tuscany and Apulia Cord Blood Banks. Results from generalized multivariable linear mixed models showed that CBV, TNC and CD34+ cell were associated with known obstetric and neonatal parameters and showed rhythmic patterns in different time domains and frequency ranges. The present findings confirm that volume, total nucleated cells and stem cells of the UCB donations are hallmarked by rhythmic patterns in different time domains and frequency ranges and suggest that temporal rhythms in addition to known obstetric and neonatal parameters influence CBV, TNC and CD34+ cell content in UBC units. PMID- 26906328 TI - Predictors of circumferential resection margin involvement in surgically resected rectal cancer: A retrospective review of 23,464 patients in the US National Cancer Database. AB - INTRODUCTION: The circumferential resection margin (CRM) is a key prognostic factor after rectal cancer resection. We sought to identify factors associated with CRM involvement (CRM+). METHODS: A retrospective review was performed of the National Cancer Database, 2004-2011. Patients with rectal cancer who underwent radical resection and had a recorded CRM were included. Multivariable analysis of the association between clinicopathologic characteristics and CRM was performed. Tumor <1 mm from the cut margin defined CRM+. RESULTS AND DISCUSSION: Of 23,464 eligible patients, 13.3% were CRM+. Factors associated with CRM+ were diagnosis later in the study period, lack of insurance, advanced stage, higher grade, undergoing APR, and receiving radiation. Nearly half of CRM+ patients did not receive neoadjuvant therapy. CRM+ patients who did not receive neoadjuvant therapy were more likely to be female, older, with more comorbidities, smaller tumors, earlier clinical stage, advanced pathologic stage, and CEA-negative disease compared to those who received it. CONCLUSIONS: Factors associated with CRM+ include features of advanced disease, undergoing APR, and lack of health insurance. Half of CRM+ patients did not receive neoadjuvant treatment. These represent cases where CRM status may be modifiable with appropriate pre-operative selection and multidisciplinary management. PMID- 26906329 TI - Pancreaticoduodenectomy for adenocarcinoma of the pancreatic head is justified in elderly patients: A Retrospective Cohort Study. AB - BACKGROUND: The increasing elderly population is an inevitable trend worldwide in developed countries. Therefore, we aimed to assess the experience of a tertiary pancreatic center with a very homogenous population comprising only patients diagnosed with PDAC of the pancreatic head in patients older than 75 years of age compared to their younger counterparts regarding the benefit in life expectancy and tumor biological aggressiveness. METHODS: 300 patients underwent partial pancreaticoduodenectomy (PD) or pylorus preserving pancreaticoduodenectomy (PPPD) for PDAC of the pancreatic head between 2002 and 2012 and were evaluated with regard to their co-morbidities, clinicopathological and perioperative variables, postoperative morbidity, mortality and long term survival. Therefore, two groups according to the age at the procedure (A: <75 years, n = 241, B: >=75 years, n = 59) were designed. RESULTS: There were no differences between groups with regard to gender, performed procedure (PPPD or PD), operation time, blood loss, tumor invasiveness and grade of tumor differentiation, R-status, lymph node ratio, 30 day mortality, length of stay and adjuvant chemotherapy. Extended resections including total pancreatectomy were slightly more often performed in younger patients (p = 0.071) and trended toward a higher rate of surgical complications in patients <75 years of age (p = 0.183). A higher rate of preoperative co morbidities in elderly patients (group B), was associated with more postoperative non-surgical complications (p = 0.002) in this group of patients. However, the median overall survival (19.2 vs. 18.4 months) did not differ significantly between groups. CONCLUSIONS: Major pancreatic surgery for ductal adenocarcinoma of the pancreatic head is justified in elderly patients. With careful patients' selection and prudent perioperative management, elderly patients will have a similar long term outcome despite the higher rate of postoperative morbidity based on non-surgical complications. PMID- 26906331 TI - Should laryngeal tubes or masks be used for out-of-hospital cardiac arrest patients? PMID- 26906330 TI - Impact of postoperative daily image-guided intensity-modulated radiotherapy on overall and local progression-free survival in patients with oral cavity cancer. AB - BACKGROUND: We compared the outcome of patients who received non-image-guided intensity-modulated radiotherapy (IMRT) with those who received helical tomotherapy (HT), a daily image-guided radiotherapy (IGRT), after surgery for oral cavity cancer (OCC). METHODS: During the period November 2006 to December 2013, a total of 152 postoperative OCC patients underwent either IMRT (n = 79) or daily IGRT (n = 73) 4 to 6 weeks after surgery. Patients in the IMRT group received 6 MV photon beams to 7 fields and those in the IGRT group received daily fractions of 1.8 or 2 Gy on five consecutive days. RESULTS: Patients who received daily IGRT had higher 5-year overall survival than those who received IMRT (87% versus 48%, p = 0.015). The local progression-free survival rate was also higher in patients who received IGRT (85% versus 58%, p = 0.006). More patients in the IGRT group completed the package of overall treatment time in <= 13 weeks and completed their course of radiation therapy in <= 8 weeks than patients in the IMRT group (89% versus 68%, p = 0.002; 84% versus 58%, p = 0.001), respectively. The rate of local failure in the primary tumor area was 24.0 % in the IMRT group and 6.8% in the IGRT group. Among patients with primary local failure, the marginal failure rate was 52.6% in the IMRT group and 0 % in the IGRT group. CONCLUSIONS: For patients with locally advanced OCC, postoperative IGRT results in better overall survival, better local progression-free survival, less marginal failure and shorter overall treatment time than postoperative non-image-guided IMRT. PMID- 26906332 TI - Potassium measurement in the ED: interpret with caution. PMID- 26906333 TI - The introduction of an esophageal heat transfer device into a therapeutic hypothermia protocol: A prospective evaluation. AB - BACKGROUND: Temperature management is a recommended part of post-resuscitation care of comatose survivors of cardiac arrest. A number of methods exist for temperature management, all of which have limitations. We aimed to evaluate the performance and ease of use of a new esophageal heat transfer device (EHTD; Advanced Cooling Therapy, Chicago, IL, USA) for temperature management of adult survivors of cardiac arrest. METHODS: We performed a prospective study from March to June 2015. Our standard protocol uses servo-controlled water blankets supplemented with ice-cold saline in order to attain goal temperature (32 degrees C-34 degrees C) within 1 hour. We substituted the EHTD for our usual water blankets, then recorded temperature over time and adverse effects. MAIN FINDINGS: A total of 14 patients were treated, with mean age 65.1+/-13.7 years, and median weight 75.5 (70; 83) kg. Initial temperature was 35.3+/-1.2 degrees C. Mean cooling rate during the induction phase was 1.12+/-0.62 degrees C/h, time to target temperature was 60 (41; 195) min and the volume of iced fluids infused was 1607+/-858 ml (as compared with 2-2.5L historically). The percentage of time outside target temperature range during the maintenance phase was 6.5% (0.0; 29.0). Rewarming rate was 0.22 (0.18; 0.31) degrees C/h. No major adverse effects were observed. CONCLUSION: Using the EHTD, our patient population attained goal temperatures in one hour, the volume of ice-cold saline required to attain this cooling rate was decreased by one-third, and experienced a low percentage of time outside target temperature range and no major adverse effects. PMID- 26906334 TI - Improved p-type conductivity in Al-rich AlGaN using multidimensional Mg-doped superlattices. AB - A novel multidimensional Mg-doped superlattice (SL) is proposed to enhance vertical hole conductivity in conventional Mg-doped AlGaN SL which generally suffers from large potential barrier for holes. Electronic structure calculations within the first-principle theoretical framework indicate that the densities of states (DOS) of the valence band nearby the Fermi level are more delocalized along the c-axis than that in conventional SL, and the potential barrier significantly decreases. Hole concentration is greatly enhanced in the barrier of multidimensional SL. Detailed comparisons of partial charges and decomposed DOS reveal that the improvement of vertical conductance may be ascribed to the stronger pz hybridization between Mg and N. Based on the theoretical analysis, highly conductive p-type multidimensional Al0.63Ga0.37N/Al0.51Ga0.49N SLs are grown with identified steps via metalorganic vapor-phase epitaxy. The hole concentration reaches up to 3.5 * 10(18) cm(-3), while the corresponding resistivity reduces to 0.7 Omega cm at room temperature, which is tens times improvement in conductivity compared with that of conventional SLs. High hole concentration can be maintained even at 100 K. High p-type conductivity in Al rich structural material is an important step for the future design of superior AlGaN-based deep ultraviolet devices. PMID- 26906335 TI - Government should apologise to junior doctors, says health policy expert. PMID- 26906336 TI - Issues related to sex differences in antipsychotic treatment. AB - PURPOSE OF REVIEW: The effectiveness, side-effect profiles, and numerous other characteristics of antipsychotic medications have been extensively studied. However, the majority of publications do not address the many potential sex differences in efficacy and doses of medications, as well as other sex-specific considerations. RECENT FINDINGS: Of studies that exist, some suggest that female patients respond to lower doses of antipsychotic medications than males and that side-effect profiles vary between the sexes. However, the majority of preclinical trials use only male laboratory animals, and human clinical trials consist of too few women to analyze their response as a separate group. SUMMARY: Although changes in hormone production occurring at multiple stages throughout a women's life (such as during pregnancy, breast feeding, menopause, and postmenopausal) are presented as too complex to deal with in clinical trials, they could instead be embraced as clinical dilemmas that require additional study and consideration. We suggest that a focus should be made to reanalyze data from existing major treatment trials of antipsychotics to determine what medications specifically provide the most efficacy for female patients and at what dose range. In addition, new prospective studies are needed to specifically address appropriate adjustments in psychopharmacologic treatment for female patients during pregnancy, and when postmenopausal. More studies of the effects of antipsychotics on male and female fetuses in utero and during breast feeding are also needed to better manage women with schizophrenia and their offspring on a long-term basis in the community. There is currently too little known about sex differences in neuropharmacology. With the new USA National Institutes of Health policy to include sex in all new proposals, the time has come to close this gap in knowledge. PMID- 26906337 TI - Prediction and prevention of preterm birth and its sequelae. PMID- 26906338 TI - High-frequency ventilation for non-invasive respiratory support of neonates. AB - Non-invasive respiratory support is increasingly used in lieu of intubated ventilator support for the management of neonatal respiratory failure, particularly in very low birth weight infants at risk for bronchopulmonary dysplasia. The optimal approach and mode for non-invasive support remains uncertain. This article reviews the application of high-frequency ventilation for non-invasive respiratory support in neonates, including basic science studies on mechanics of gas exchange, animal model investigations, and a review of current clinical use in human neonates. PMID- 26906339 TI - Risk assessment and management to prevent preterm birth. AB - Preterm birth is the most important cause of neonatal mortality and morbidity worldwide. In this review, we review potential risk factors associated with preterm birth and the subsequent management to prevent preterm birth in low and high risk women with a singleton or multiple pregnancy. A history of preterm birth is considered the most important risk factor for preterm birth in subsequent pregnancy. General risk factors with a much lower impact include ethnicity, low socio-economic status, maternal weight, smoking, and periodontal status. Pregnancy-related characteristics, including bacterial vaginosis and asymptomatic bacteriuria, appear to be of limited value in the prediction of preterm birth. By contrast, a mid-pregnancy cervical length measurement is independently associated with preterm birth and could be used to identify women at risk of a premature delivery. A fetal fibronectin test may be of additional value in the prediction of preterm birth. The most effective methods to prevent preterm birth depend on the obstetric history, which makes the identification of women at risk of preterm birth an important task for clinical care providers. PMID- 26906340 TI - Highly Stable Nanocontainer of APTES-Anchored Layered Titanate Nanosheet for Reliable Protection/Recovery of Nucleic Acid. AB - A universal technology for the encapsulative protection of unstable anionic species by highly stable layered metal oxide has been developed via the surface modification of a metal oxide nanosheet. The surface anchoring of (3 aminopropyl)triethoxysilane (APTES) on exfoliated titanate nanosheet yields a novel cationic metal oxide nanosheet, which can be universally used for the hybridization with various biological and inorganic anions. The encapsulation of deoxyribonucleic acid (DNA) in the cationic APTES-anchored titanate lattice makes possible the reliable long-term protection of DNA against enzymatic, chemical, and UV-vis light corrosions. The encapsulated DNA can be easily released from the titanate lattice via sonication, underscoring the functionality of the cationic APTES-anchored titanate nanosheet as a stable nanocontainer for DNA. The APTES anchored titanate nanosheet can be also used as an efficient CO2 adsorbent and a versatile host material for various inorganic anions like polyoxometalates, leading to the synthesis of novel intercalative nanohybrids with unexplored properties and useful functionalities. PMID- 26906341 TI - Monte Carlo dosimetry of the IRAsource high dose rate (192)Ir brachytherapy source. AB - High-dose-rate (HDR) brachytherapy is a common method for cancer treatment in clinical brachytherapy. Because of the different source designs, there is a need for specific dosimetry data set for each HDR model. The purpose of this study is to obtain detailed dose rate distributions in water phantom for a first prototype HDR (192)Ir brachytherapy source model, IRAsource, and compare with the other published works. In this study, Monte Carlo N-particle (MCNP version 4C) code was used to simulate the dose rate distributions around the HDR source. A full set of dosimetry parameters reported by the American Association of Physicists in Medicine Task Group No. 43U1 was evaluated. Also, the absorbed dose rate distributions in water, were obtained in an along-away look-up table. The dose rate constant, Lambda, of the IRAsource was evaluated to be equal to 1.112 +/- 0.005 cGy h(-1) U(-1). The results of dosimetry parameters are presented in tabulated and graphical formats and compared with those reported from other commercially available HDR (192)Ir sources, which are in good agreement. This justifies the use of specific data sets for this new source. The results obtained in this study can be used as input data in the conventional treatment planning systems. PMID- 26906342 TI - Understanding the High Activity of Fe-N-C Electrocatalysts in Oxygen Reduction: Fe/Fe3C Nanoparticles Boost the Activity of Fe-N(x). AB - Understanding the origin of high activity of Fe-N-C electrocatalysts in oxygen reduction reaction (ORR) is critical but still challenging for developing efficient sustainable nonprecious metal catalysts in fuel cells and metal-air batteries. Herein, we developed a new highly active Fe-N-C ORR catalyst containing Fe-N(x) coordination sites and Fe/Fe3C nanocrystals (Fe@C-FeNC), and revealed the origin of its activity by intensively investigating the composition and the structure of the catalyst and their correlations with the electrochemical performance. The detailed analyses unambiguously confirmed the coexistence of Fe/Fe3C nanocrystals and Fe-N(x) in the best catalyst. A series of designed experiments disclosed that (1) N-doped carbon substrate, Fe/Fe3C nanocrystals or Fe-N(x) themselves did not deliver the high activity; (2) the catalysts with both Fe/Fe3C nanocrystals and Fe-N(x) exhibited the high activity; (3) the higher content of Fe-N(x) gave the higher activity; (4) the removal of Fe/Fe3C nanocrystals severely degraded the activity; (5) the blocking of Fe-N(x) downgraded the activity and the recovery of the blocked Fe-N(x) recovered the activity. These facts supported that the high ORR activity of the Fe@C-FeNC electrocatalysts should be ascribed to that Fe/Fe3C nanocrystals boost the activity of Fe-N(x). The coexistence of high content of Fe-N(x) and sufficient metallic iron nanoparticles is essential for the high ORR activity. DFT calculation corroborated this conclusion by indicating that the interaction between metallic iron and Fe-N4 coordination structure favored the adsorption of oxygen molecule. These new findings open an avenue for the rational design and bottom-up synthesis of low-cost highly active ORR electrocatalysts. PMID- 26906343 TI - Obligatory Effort [Hishtadlut] as an Explanatory Model: A Critique of Reproductive Choice and Control. AB - Studies on reproductive technologies often examine women's reproductive lives in terms of choice and control. Drawing on 48 accounts of procreative experiences of religiously devout Jewish women in Israel and the US, we examine their attitudes, understandings and experiences of pregnancy, reproductive technologies and prenatal testing. We suggest that the concept of hishtadlut-"obligatory effort" works as an explanatory model that organizes Haredi women's reproductive careers and their negotiations of reproductive technologies. As an elastic category with negotiable and dynamic boundaries, hishtadlut gives ultra-orthodox Jewish women room for effort without the assumption of control; it allows them to exercise discretion in relation to medical issues without framing their efforts in terms of individual choice. Haredi women hold themselves responsible for making their obligatory effort and not for pregnancy outcomes. We suggest that an alternative paradigm to autonomous choice and control emerges from cosmological orders where reproductive duties constitute "obligatory choices." PMID- 26906344 TI - Development of a sensitive molecular detection assay for mango malformation disease caused by Fusarium mangiferae. AB - OBJECTIVES: To develop a sensitive and specific molecular assay for detection of mango malformation disease (MMD), which is caused primarily by Fusarium mangiferae. RESULTS: We screened 100 ISSR primers and identified one (UBC888) that directed the stable amplification of a specific gene fragment of 479 bp (GenBank accession number KJ526382). Based on the DNA sequence of this fragment, a pair of SCAR primers (W342 and W1772) were designed to amplify another gene fragment of 1376 bp (GenBank accession number KJ526383), demonstrating the successful conversion of an ISSR marker to a SCAR marker. An effective and simple detection assay for MMD was established based on this pair of PCR primers, with a high level of specificity and sensitivity to the DNA of F. mangiferae and other species of Fusarium both in vitro and in vivo. It can detect as little as 10 pg fungal DNA from the DNA of mango's tissues. CONCLUSIONS: Our assay provides a practical method for the early diagnosis so that proper prevention of the mango malformation disease can be developed. PMID- 26906345 TI - SMAS Fusion Zones Determine the Subfascial and Subcutaneous Anatomy of the Human Face: Fascial Spaces, Fat Compartments, and Models of Facial Aging. AB - BACKGROUND: Fusion zones between superficial fascia and deep fascia have been recognized by surgical anatomists since 1938. Anatomical dissection performed by the author suggested that additional superficial fascia fusion zones exist. OBJECTIVES: A study was performed to evaluate and define fusion zones between the superficial and the deep fascia. METHODS: Dissection of fresh and minimally preserved cadavers was performed using the accepted technique for defining anatomic spaces: dye injection combined with cross-sectional anatomical dissection. RESULTS: This study identified bilaminar membranes traveling from deep to superficial fascia at consistent locations in all specimens. These membranes exist as fusion zones between superficial and deep fascia, and are referred to as SMAS fusion zones. CONCLUSIONS: Nerves, blood vessels and lymphatics transition between the deep and superficial fascia of the face by traveling along and within these membranes, a construct that provides stability and minimizes shear. Bilaminar subfascial membranes continue into the subcutaneous tissues as unilaminar septa on their way to skin. This three dimensional lattice of interlocking horizontal, vertical, and oblique membranes defines the anatomic boundaries of the fascial spaces as well as the deep and superficial fat compartments of the face. This information facilitates accurate volume augmentation; helps to avoid facial nerve injury; and provides the conceptual basis for understanding jowls as a manifestation of enlargement of the buccal space that occurs with age. PMID- 26906346 TI - Content of Soluble Factors and Characteristics of Stromal Vascular Fraction Cells in Lipoaspirates from Different Subcutaneous Adipose Tissue Depots. AB - BACKGROUND: Although fat grafting has emerged as a major force in plastic, reconstructive, and aesthetic surgery, some questions regarding its reliability and regenerative potential remain unanswered. OBJECTIVES: The authors examined the influence of three anatomic areas on various lipoaspirate properties to identify the most appropriate harvest site for fat-grafting procedures. METHODS: Lipoaspirates from 25 healthy patients were harvested from the abdomen, inner thigh, and knee. The authors measured the content of soluble factors in the lipoaspirate followed by the assessment of the yield, adipogenic differentiation, proliferation of stromal vascular fraction (SVF) cells, and the percentage of adipose-derived stem cells (ASC) in the SVF. The results also were correlated with the age and body mass index of the donors. RESULTS: Lipoaspirates from the abdomen showed significantly higher concentrations of matrix metalloproteinase (MMP)-9 compared with the knee. The content of basic fibroblast growth factor (b FGF), platelet-derived growth factor (PDGF)-BB, and insulin-like growth factor (IGF)-1 tended to be highest in the abdomen but did not reach statistical significance. Vascular endothelial growth factor (VEGF)-A and bFGF-2 contents both correlated negatively with age in lipoaspirates from at least two different anatomic areas. CONCLUSIONS: The authors' results indicate that the abdomen may be a slight favorite over the inner thigh and knee because of its richer content of soluble factors. However, because only the difference of MMP-9 content actually reached statistical significance and because no differences in SVF characteristics were observed, a decision primarily based on other criteria appears to be justifiable. PMID- 26906347 TI - Gel Fracture of Highly Cohesive Gel Implants on Insertion: Diagnostic Difficulties. PMID- 26906348 TI - Micro-Shuttle Lifting of the Neck: A Percutaneous Loop Suspension Method Using a Novel Double-Ended Needle. AB - BACKGROUND: Most younger patients expect to be able to achieve significant improvements and lift to their neck, yet they don't want to undergo extensive surgery. They are now able to do that and restore their youthful appearance thanks to new concepts the techniques through volume redistribution. OBJECTIVES: The authors' goal was to achieve results that are comparable to a necklift and durable through minimally invasive surgery, utilizing punctures instead of incisions. METHODS: The concept of micro-shuttle lifting creates a percutaneous hammock to achieve the lifting of all different planes of the neck at once. This is accomplished by putting nonabsorbable sutures on nonundermined platsyma through the use of a double-ended (micro-shuttle) needle and anchoring it to fixed thread loops around the ears. Mitigation of gravitational force is accomplished through the loop suspensions, to obtain effective skin redraping over the suture-created internal splint. RESULTS: This combined technique for the neck was applied in 221 selected patients between December 2005 and May 2014, with follow-up ranging from 8 months to 7 years. The mean age of the patients was 42.5 years. Outcomes were satisfactory in all but 12 cases, of which 7 found the result inadequate. The operation time for the neck was less than 40 minutes under local anesthesia or local anesthesia with sedation, and the recovery time was 5-7 days. CONCLUSIONS: The sustainability of this percutaneous procedure does not rely on the suspensions, but rather on the skin redraping in the new position in a similar manner to orthopedic fracture treatment. In selected patients, this safe and simple percutaneous necklifting method can be quickly and easily performed under local anesthesia with long-term durability, low morbidity, and a high patient satisfaction rate. LEVEL OF EVIDENCE 4: Therapeutic. PMID- 26906349 TI - Hijacked Journals: An Emerging Challenge for Scholarly Publishing. PMID- 26906350 TI - Brachioplasty by Power-Assisted Liposuction and Fat Transfer: A Novel Approach That Obviates Skin Excision. AB - BACKGROUND: Current brachioplasty techniques include excisional surgery alone or in combination with liposuction. These techniques are associated with poor outcomes, such as residual contour deformities and unfavorable scarring. OBJECTIVES: The authors proposed a new classification system and treatment algorithm for brachial ptosis and described their experience with power-assisted liposuction and lipofilling to treat brachial ptosis without excisional surgery. METHODS: Ninety-five patients with grades 1, 2, or 3 brachial ptosis who underwent brachioplasty were evaluated in a prospective study. Power-assisted liposuction was applied to the posterior arm and para-axillary region, and power assisted lipofilling was applied to the so-called "bicipital triangle" of the medial arm. RESULTS: The patients' mean age was 39 years, mean body mass index was 28 kg/m(2), mean lipoaspirate volume was 240 mL per arm, and mean fat injection volume was 110 mL per side. The mean operating time was 50 minutes, and the average follow-up period was 24 months. Hematoma developed in 2 patients who underwent brachioplasty in combination with another body contouring procedure (1 abdominal hematoma and 1 thigh hematoma; 2.1% complication rate). No other complications were recorded. CONCLUSIONS: Brachioplasty by means of power assisted liposuction and lipofilling is a safe and reliable option that obviates excisional surgery in patients with mild to moderate brachial ptosis. LEVEL OF EVIDENCE: 4 Therapeutic. PMID- 26906351 TI - Vertical Sculpted Pillar Reduction Mammaplasty in 317 Patients: Technique, Complications, and BREAST-Q Outcomes. AB - BACKGROUND: The senior author (JCG) has described the vertical sculpted pillar breast reduction. OBJECTIVES: This manuscript aimed to compare this technique's safety profile to other established techniques via complication rate reporting. Few studies have utilized the BREAST-Q for long-term outcomes reporting in bilateral reduction mammaplasty patients. BREAST-Q outcome comparisons, between cosmetic and insurance-based breast reduction cohorts, have not been previously reported. METHODS: A retrospective chart review was performed on patients who underwent reduction mammaplasty using the vertical sculpted pillar technique. The BREAST-Q postoperative reduction mammaplasty module was administered. Complication rates and outcomes data were compared among patient cohorts distinguished by pedicle, scar pattern, and payor population. Statistically significant differences were set at P < .05. RESULTS: Compared to the superior pedicle, use of the superomedial pedicle statistically increased rates of postoperative fat necrosis in this series. Complication rates did not differ among scar patterns, but use of a J, L-shaped, or short-T scar decreased the need for secondary/revisional surgery. Cosmetic and insurance-based outcomes did not differ in any domain of the postoperative reduction mammaplasty BREAST-Q module. CONCLUSIONS: Complications data for the vertical sculpted pillar reduction mammaplasty were comparable to published results for other techniques. Complication rates are unaffected by scar pattern. Superomedial pedicle selection and larger insurance-based reductions may predispose to statistically significant increases in fat necrosis compared to use of the superior pedicle. Payor source neither affects the majority of complication rates, nor BREAST-Q satisfaction and quality of life domains. This information can be used to improve management of expectations during the preoperative consultation process. LEVEL OF EVIDENCE: 4 Therapeutic. PMID- 26906353 TI - Editorial: Translational Alzheimer's Disease Research. PMID- 26906352 TI - Management of Bronchiolitis in Community Hospitals in Ontario: a Multicentre Cohort Study. AB - OBJECTIVES: Bronchiolitis is the leading cause of hospital admission for infants, but few studies have examined management of this condition in community hospital settings. We reviewed the management of children with bronchiolitis presenting to community hospitals in Ontario. METHODS: We retrospectively reviewed a consecutive cohort of infants less than 12 months old with bronchiolitis who presented to 28 Ontario community hospitals over a two-year period. Bronchiolitis was defined as first episode of wheezing associated with signs of an upper respiratory tract infection during respiratory syncytial virus season. RESULTS: Of 543 eligible children, 161 (29.7%, 95% Confidence Interval (CI) 22.3 to 37.0%) were admitted to hospital. Hospital admission rates varied widely (Interquartile Range 0%-40.3%). Bronchodilator use was widespread in the emergency department (ED) (79.7% of patients, 95% CI 75.0 to 84.5%) and on the inpatient wards (94.4% of patients, 95% CI 90.2 to 98.6%). Salbutamol was the most commonly used bronchodilator. At ED discharge 44.7% (95% CI 37.5 to 51.9%) of patients were prescribed a bronchodilator medication. Approximately one-third of ED patients (30.8%, 95% CI 22.7 to 38.8%), 50.3% (95% CI 37.7 to 63.0%) of inpatients, and 23.5% (95% CI 14.4 to 32.7) of patients discharged from the ED were treated with corticosteroids. The most common investigation obtained was a chest x-ray (60.2% of all children; 95% CI 51.9 to 68.5%). CONCLUSIONS: Infants with bronchiolitis receive medications and investigations for which there is little evidence of benefit. This suggests a need for knowledge translation strategies directed to community hospitals. PMID- 26906354 TI - Peripheral Blood Adipokines and Insulin Levels in Patients with Alzheimer's Disease: A Replication Study and Meta-Analysis. AB - BACKGROUND: Although peripheral blood adipokines and insulin levels have been considered to be biomarkers of Alzheimer's disease (AD), previous researches about levels of adipokines and insulin in blood are no conclusive. We designed this meta-analysis to validate whether peripheral adipokines and insulin can be used as a candidate biomarker in AD diagnosis. METHODS: We carried out a replication study in serum by ourselves and further conducted a meta-analysis to estimate the different levels of peripheral blood adipokines and insulin between AD patients and controls. In the section of meta-analysis, the pooled weighted mean difference (WMD) and 95% confidence interval (CI) was used to compare the levels of adipokines and insulin in different groups. RESULTS: According to our replication study, there is statistically significant lower in the levels of leptin, but conspicuous higher in the levels of adiponectin and insulin in the blood of AD patients than controls. We finally identified four studies for leptin, four studies for adiponectin and eleven studies for insulin. From the random-effect model, the pooled WMD of the levels of leptin, adiponectin and insulin of AD subjects compared with the controls was -3.90 ng/ml (95% CI: [ 5.68, -2.13]), 9.42 ug/mL (95% CI: [4.21, 14.62]), and 2.86 uIU/ml (95% CI: [1.21, 4.50]), respectively. CONCLUSION: Our replication study and meta-analysis support lower levels of leptin and higher levels of adiponectin and insulin in AD patients with respect to controls, and indicate their potential values as important risk factors for AD. Further researches that using standardized assay for leptin, adiponectin, and insulin measurement are still needed to reveal the potential change of peripheral blood leptin, adiponectin, and insulin levels in AD participants. PMID- 26906355 TI - Functional Activity and Connectivity Differences of Five Resting-State Networks in Patients with Alzheimer's Disease or Mild Cognitive Impairment. AB - We aimed to investigate the activity within and the connectivity between resting state networks (RSNs) in healthy subjects and patients with Alzheimer's disease (AD) or mild cognitive impairment (MCI). Magnetic resonance imaging (MRI) and resting-state MRI were performed on patients diagnosed with AD (n=18) or MCI (n=16) and on healthy subjects (n=18) with matching demographic characteristics (age, sex, and education level). Independent component analysis and Granger causality analysis (GCA) were used during image postprocessing. We calculated 'In + Out degree' for each RSN. Then, we investigated the relationships between "In + Out degree" of each brain network and the cognitive behavioural data. RSNs were obtained using the optimal matching method. The core areas of the five RSNs were similar between the AD, MCI, and healthy control groups, but the activity within these five RSNs was significantly lower in the AD and MCI groups than in the healthy control group (P<0.01, false discovery rate corrected). The GCA results showed that the connectivity between the five RSNs, particularly the connectivity from the default mode network (DMN) to the other RSNs, was slightly lower in MCI patients and was significantly lower in AD patients than in healthy subjects. In contrast, increased connectivity was evident between the memory network and the executive control network in the AD and MCI patients. The "In + Out degree" of the DMN negatively correlated with the Montreal Cognitive Assessment score in AD patients (R=-0.43, P<0.05). In conclusion, the activity within RSNs and the connectivity between RSNs differed between AD patients, MCI patients, and normal individuals; these results provide an imaging reference for the diagnosis of AD and the measurement of disease progression and reveal insight into the pathogenesis of AD. PMID- 26906358 TI - Demonstration of snapshot imaging polarimeter using modified Savart polariscopes. AB - In an earlier publication, [Appl. Opt.51, 5791 (2012)] we demonstrated by theoretical analysis that a snapshot imaging polarimeter using modified Savart polariscopes (MSP-SIP) is comparable in carrier frequency, signal-to-noise ratio, and spatial resolution to a snapshot imaging polarimeter using conventional Savart polariscopes. In this investigation, numerical simulation is used to demonstrate the feasibility of MSP-SIP and investigate the limitation of the filtration and the Fourier analysis decoupling the polarization information encoded through the spatial modulation. In addition, a laboratory experiment is conducted to demonstrate the validity of MSP-SIP. The MSP-SIP operates on the principle of encoding polarization information within the spatial modulation of the image. This unique technology allows all Stokes parameters to be simultaneously recorded from every spatial position in an image with a single integration period of the imaging system. The device contains no moving parts and requires no scanning, allowing it to acquire data without the motion artifacts normally associated with a scanning polarimeter. In addition to snapshot imaging and static (no moving parts) capabilities, image processing is simple, and the device is compact and miniature. Therefore, we believe that MSP-SIP will be useful in many applications, such as remote sensing and bioscience. PMID- 26906356 TI - Cytoskeletal Pathologies of Age-Related Diseases between Elderly Sri Lankan (Colombo) and Indian (Bangalore) Brain Samples. AB - Within South Asia, Sri Lanka represents fastest aging with 13% of the population was aged over 60's in 2011, whereas in India it was 8%. Majority of the Sri Lankan population based genetic studies have confirmed their origin on Indian mainland. As there were inadequate data on aging cytoskeletal pathologies of these two nations with their close genetic affiliations, we performed a comparison on their elderly. Autopsy brain samples of 50 individuals from Colombo, Sri Lanka (mean age 72.1 yrs +/- 7.8, mean +/- S.D.) and 42 individuals from Bangalore, India (mean age 65.9 yrs +/- 9.3) were screened for neurodegenerative pathologies using immunohistochemical techniques. A total of 79 cases with incomplete clinical history (Colombo- 47 and Bangalore- 32) were subjected to statistical analysis and 13 cases, clinically diagnosed with dementia and/or Parkinsonism disorders were excluded. As per National Institute on Aging- Alzheimer's Association guidelines, between Colombo and Bangalore samples, Alzheimer's disease neuropathologic change for intermediate/ high level was 4.25% vs. 3.12% and low level was 19.15% vs. 15.62% respectively. Pathologies associated with Parkinsonism including brainstem predominant Lewy bodies- 6.4% and probable progressive supra nuclear palsy- 2.13% were found solely in Colombo samples. Alzheimer related pathologies were not different among elders, however, in Colombo males, neurofibrillary tangle grade was significantly higher in the region of hippocampus (odds ratio = 1.46, 95% confidence interval = 0.07-0.7) and at risk in midbrain substantia nigra (p = 0.075). Other age-related pathologies including spongiform changes (p < 0.05) and hippocampus cell loss in dentate gyrus region (p < 0.05) were also identified prominently in Colombo samples. Taken together, aging cytoskeletal pathologies are comparatively higher in elderly Sri Lankans and this might be due to their genetic, dietary and/ or environmental variations. PMID- 26906357 TI - Triptolide Rescues Spatial Memory Deficits and Amyloid-beta Aggregation Accompanied by Inhibition of Inflammatory Responses and MAPKs Activity in APP/PS1 Transgenic Mice. AB - Alzheimer's disease (AD) is the most prevalent neurodegenerative disease characterized by aggregation of amyloid-beta (Abeta) peptide in the hippocampus and cortex of brain. Neuroinflammation is considered a driving force of the progression of cognitive decline in AD. During the neuroinflammatory process, activated astrocytes and microglia induced by Abeta peptide produce pro inflammatory factors and neurotoxins, which promote neurodegeneration in AD brain, eventually dementia. Thus, the suppression of glial over-activation in AD brain might result in therapeutic effect. Triptolide, a natural compound extracted from the Chinese medicinal herb Tripterygium wilfordii Hook F., has shown anti-inflammatory effects. Whether triptolide exhibits preventive effects on AD-like pathology via anti-inflammatory action is unclear. The present study showed that intraperitoneal injection of triptolide (20 MUg/kg) for 15 weeks markedly alleviated deficits in learning and memory, and prevented Abeta accumulation in the brain of AD transgenic mice (APP/PS1 mice). These results were accompanied by reduction in glial activation and contents of pro inflammatory factors in the brain of APP/PS1 mice treated by triptolide compared to saline-treated APP/PS1 mice. In addition, we observed that the Mitogen activated protein kinases (MAPKs, including p38, ERK and JNK) phosphorylation was also suppressed by treatment of triptolide in the brain of APP/PS1 mice. Taken together, our study suggests that molecular mechanisms underlying the therapeutic effects of triptolide on the AD model might involve inhibition of the neuroinflammation by suppressing MAPKs activity. PMID- 26906359 TI - Experimental characterization of the hygroscopic properties of wood during convective drying using digital holographic interferometry. AB - In this paper, an application of digital holography for the measurement of surface deformations and the strain field to understand the shrinkage behavior of wood during convective drying is presented. Moisture absorption and desorption induce the dimensional changes and deformations in wood that leads to failure of certain components made of wood. The knowledge of the dimensional changes in wood, deformations, strain distribution and their causes are important for the best utilization of wood. For the study, lensless Fourier transform digital holographic interferometry is used to measure moisture- induced deformation, strain distribution, and the coefficient of hygroscopic shrinkage in different samples of wood. The technique is highly sensitive and enables the observation of deformation and strain distribution during the variations of moisture content in the wood. The wet wood sample was exposed to convective drying, which leads to changes in the moisture content and the associated deformations. The deformation/strain in each step of drying process is used to evaluate the coefficient of hygroscopic shrinkage in different wood samples. The experiments were repeated for differently treated woods. The experimental results show that the strain and coefficient of hygroscopic shrinkage can be minimized if the wood is dried in the presence of the proper moisture content. PMID- 26906360 TI - Low-power variable optical attenuator based on a hybrid SiON-polymer S-bend waveguide. AB - We propose a low-power variable optical attenuator based on the configuration of a hybrid silicon oxynitride (SiON)-polymer S-bend waveguide and two grooves in both sides of the S-bend waveguide core. With such a configuration, the opposite thermo-optic characteristics of SiON and polymer materials can be fully utilized. As a consequence, the heat utilization efficiency is increased. Theoretical simulation shows that an optical attenuation of ~50 dB can be achieved with an applied electrical power of 3.6 mW. A typical fabricated device, which has a total length of 8 mm, shows a maximum optical attenuation of 46 dB with an applied electrical power of 16.2 mW and an insertion loss of 5.4 dB. PMID- 26906361 TI - All-fiber reflecting temperature probe based on the simplified hollow-core photonic crystal fiber filled with aqueous quantum dot solution. AB - An all-fiber reflecting fluorescent temperature probe is proposed based on the simplified hollow-core photonic crystal fiber (SHC-PCF) filled with an aqueous CdSe/ZnS quantum dot solution. SHC-PCF is an excellent PCF used to fill liquid materials, which has low loss transmission bands in the visible wavelength range and enlarged core sizes. Both end faces of the SHC-PCF were spliced with multimode fiber after filling in order to generate a more stable and robust waveguide structure. The obtained temperature sensitivity dependence of the emission wavelength and the self-referenced intensity are 126.23 pm/ degrees C and -0.007/ degrees C in the temperature range of -10 degrees C-120 degrees C, respectively. PMID- 26906362 TI - Small roll angle measurement using lateral shearing cyclic path polarization interferometry. AB - We present a technique for the measurement of roll angular displacement of a rotary stage using a lateral shearing cyclic path optical configuration (CPOC) setup and polarization phase shifting interferometry (PPSI). The CPOC setup, aligned on the rotary stage, laterally shears the input plane polarized spherical beam into a pair of orthogonally polarized beams, which when brought to the same state of polarization by a polarizer produce interference fringes similar to Young's fringes. Rotation of the CPOC setup in its plane introduces a phase change between the orthogonally polarized lateral sheared beams due to the change in angle of incidence of the input beam. The change in the phase results in spatial displacement of the interference fringes. Using PPSI, the phase, or the optical path difference change between the laterally sheared beams that is related to the rotation angle of the CPOC setup, is measured. PMID- 26906363 TI - Performance of a ruthenium beam separator used to separate soft x rays from light generated by a high-order harmonic light source. AB - We describe the design and fabrication of a ruthenium beam separator used to simultaneously attenuate infrared light and reflect soft x rays. Measurements in the infrared and soft x-ray regions showed the beam separator to have a reflectivity of 50%-85% in the wavelength region from 6 to 10 nm at a grazing incidence angle of 7.5 deg and 4.3% at 800 nm and the same angle of grazing incidence, indicating that the amount of attenuation is 0.05-0.09. These results show that this beam separator could provide an effective means for separating IR light from soft x rays in light generated by high-order harmonic generation sources. PMID- 26906364 TI - Hybrid wide-band, low-phase-noise scheme for Raman lasers in atom interferometry by integrating an acousto-optic modulator and a feedback loop. AB - We report a hybrid scheme for phase-coherent Raman lasers with low phase noise in a wide frequency range. In this scheme, a pair of Raman lasers with a frequency difference of 3.04 GHz is generated by the +/-1-order diffracted lights of an acousto-optic modulator (1.52 GHz), where a feedback loop is simultaneously applied for suppressing the phase noise. The beat width of the Raman lasers is narrower than 3 Hz. In the low-frequency range, the phase noise of the Raman lasers is suppressed by 35 dB with the feedback. The phase noise is less than 109 dBc/Hz in the high-frequency range. The sensitivity of an atom gyroscope employing the hybrid Raman lasers can be implicitly improved 10 times. Due to the better high-frequency response, the sensitivity is not limited by the durations of Raman pulses. This work is important for improving the performance of atom interferometer-based measurements. PMID- 26906365 TI - Model-based optimization of gravity sagging for a horizontally mounted optical flat. AB - A practical and generalized model-based gravity sagging reconstruction method for a horizontally mounted optical flat is proposed. It is a practical and generalized approach based on the finite element method (FEM) model and real experiment results. Gravity sagging and misalignment parameters are retrieved by solving the multivariable unconstrained optimization problem with a least squares sense. Finally, the accurate true surface figure can be obtained by subtracting the optimized gravity sagging from the test result in the practical mounting state. A reasonable agreement with the outcomes of the FEM analysis and the real experiment is achieved through the proposed method. The effectiveness of the method was verified by comparison with the result measured by three-flat calibration. Experimental results demonstrated that this reverse optimization method can effectively reconstruct the sagging information due to gravity, is generalized, and is computationally efficient in practice. PMID- 26906366 TI - Passively Q-switched erbium-doped fiber laser at C-band region based on WS2 saturable absorber. AB - We demonstrate a Q-switched erbium-doped fiber laser using tungsten disulfide (WS2) as a saturable absorber. The WS2 is deposited onto fiber ferrules using a drop-casting method. Passive Q-switched pulses operating in the C-band region with a central wavelength of 1560.7 nm are successfully generated by a tunable pulse repetition rate ranging from 27.2 to 84.8 kHz when pump power is increased from 40 to 220 mW. At the same time, the pulse width decreases from a maximum value of 3.84 MUs to a minimum value of 1.44 MUs. The signal-to-noise ratio gives a stable value of 43.7 dB. The modulation depth and saturation intensity are measured to be 0.99% and 36.2 MW/cm2, respectively. PMID- 26906367 TI - Cascade six-level phase-mask achromatic coronagraph. AB - A cascade six-level phase-mask achromatic coronagraph is proposed. We show that, for the ideal aberration-free case, the average suppression of the central starlight in a three-stage six-level phase-mask achromatic coronagraph (SLPMC) can reach about 10-8 over a 40% bandwidth. We also do the optimization analysis of the working wavelength of each phase mask in the three-stage SLPMC. With optimization, the starlight can be stably suppressed to less than 10-8 (average about 10-10) over the whole 40% bandwidth. PMID- 26906368 TI - Optical security devices using nonuniform schlieren texture of UV-curable nematic liquid crystal. AB - We proposed and quantitatively evaluated an optical security device that provides nonuniform or random patterns of schlieren texture in nematic liquid crystal as unique identification information with a design by employing computer image processing and normalized cross correlation. Using the same photomask as the first author's university logo, the written patterns, which were composed of polymerized isotropic areas and polymerized nematic areas, were stable among different cells. Judging from the maximum correlation coefficient of 0.09, the patterns of the schlieren texture were unique in different cells. These results indicate that photocurable nematic liquid crystal materials have the potential to be applied to security devices for anticounterfeiting measures. PMID- 26906369 TI - Reverse pillar chalcogenide glass waveguides with ultraflat and low dispersion profile over an ultrawide bandwidth. AB - Two types of reverse pillar integrated chalcogenide glass (As2S3) waveguides are proposed in this study. These geometries exhibit an ultraflat and low dispersion profile with four zero dispersion wavelengths. Its low dispersion is approximately +/-10 ps/nm/km over a 2240 nm bandwidth (for L waveguide) and +/ 13 ps/nm/km over a 2030 nm bandwidth (for F waveguide). Waveguide dispersion engineering is achieved by tuning the structural parameters of the waveguide, which has less sensitivity to the variations of structural parameters compared with silicon pillar waveguides. Moreover, the nonlinear coefficient and phase matching condition in four-wave mixing (FWM) showed a great potential for broadband FWM processes in the near- and middle-infrared regions. PMID- 26906370 TI - Broadband linearized analog intersatellite microwave photonic link using a polarization modulator in a Sagnac loop. AB - A novel orthogonal polarization optical carrier suppression with carrier (OCS+C) modulation and a coherent balanced detection intersatellite microwave photonic link with improved signal-to-noise and distortion ratio (SNDR) is proposed. By bidirectional use of a polarization modulator in a Sagnac loop in conjunction with a polarization beam splitter and two polarization controllers, only the light wave along the clockwise direction is effectively modulated while the counterclockwise light wave is not modulated due to the velocity mismatch, which generates the orthogonal polarization OCS+C modulation signal to mitigate the third-order intermodulation distortion (IMD3) and the signal-amplifier spontaneous emission beating noise. By demultiplexing and adjusting the polarization of the orthogonal polarization OCS+C modulation signal, coherent balanced detection can be realized without a local oscillator signal in the receiver, which suppresses the second-order distortions. Thus, a broadband linearized intersatellite microwave photonic link with high SNDR is achieved. Simulation results show that the maximum SNDR of 36.2 dB can be obtained when the optimum modulation index is 0.26, which is 8 dB higher than our previously proposed intersatellite microwave photonic link with an optical preamplifier. PMID- 26906371 TI - Design of high Q-factor metallic nanocavities using plasmonic bandgaps. AB - The surface plasmon polariton modes often excited in metallic nanocavities enable the miniaturization of photonic devices, even beyond the diffraction limit, yet their severe optical losses deteriorate device performance. This study proposes a design of metallic nanorod cavities coupled to plasmonic crystals with the aim of reducing the radiation loss of surface plasmon modes. Periodic Ag disks placed on an insulator-metal substrate open a substantial amount of plasmonic bandgaps (e.g., Deltalambda=290 nm at lambda=1550 nm) by modifying their diameter and thickness. When an Ag nanorod with a length of ~400 nm is surrounded by the periodic Ag disks, its Q-factor increases up to 127, yielding a 16-fold enhancement compared with a bare Ag nanorod, while its mode volume can be as small as 0.03(lambda/2n)3. Ag nanorods with gradually increasing lengths exhibit high Q-factor plasmonic modes that are tunable within the plasmonic bandgap. These numerical studies on low-radiation-loss plasmonic modes excited in metallic nanocavities will promote the development of ultrasmall plasmonic devices. PMID- 26906372 TI - Flexible calibration method for an inner surface detector based on circle structured light. AB - A new calibration method for an inner surface detector based on circle structured light is proposed in this study. Compared with existing methods, this technique is more flexible and practical and only requires a blank planar board and an additional camera, which is precalibrated under the detector's coordinate system. The board is observed by the detector and the additional camera at a few (at least two) different orientations, which need not be known. The mathematical model of this method considers different alignment errors, which are disregarded in existing methods; therefore, precise assembly is not required. The binocular intersection algorithm is used to calculate the coordinates of the calibration points. The measurement system calibrated by this method performs well in the field test in which the maximum relative error of the measured values is less than 0.18%. The experimental result indicates that this method is highly accurate and can be easily applied in inner surface detection. PMID- 26906373 TI - Extended focused imaging and depth map reconstruction in optical scanning holography. AB - In conventional microscopy, specimens lying within the depth of field are clearly recorded whereas other parts are blurry. Although digital holographic microscopy allows post-processing on holograms to reconstruct multifocus images, it suffers from defocus noise as a traditional microscope in numerical reconstruction. In this paper, we demonstrate a method that can achieve extended focused imaging (EFI) and reconstruct a depth map (DM) of three-dimensional (3D) objects. We first use a depth-from-focus algorithm to create a DM for each pixel based on entropy minimization. Then we show how to achieve EFI of the whole 3D scene computationally. Simulation and experimental results involving objects with multiple axial sections are presented to validate the proposed approach. PMID- 26906375 TI - Spot event detection along a large-scale sensor based on ultra-weak fiber Bragg gratings using time-frequency analysis. AB - A simple scheme for interrogating a 5 m long photonics device and its potential applications to quasi-distributed fiber sensing is proposed. The sensor consists of an array of 500 identical, very weak fiber Bragg gratings (FBGs). The gratings are 9 mm long and have been serially written in cascade along a single optical fiber. The measurement system is based on a combination of optical time domain reflectometry and frequency scanning of the interrogating pulse. The time frequency analysis is performed by launching an optical pulse into the sensor and retrieving and analyzing the back-reflected signal. The measurement of the temperature, length, and position of spot events along the sensors is demonstrated with good accuracy. As both spatial and temperature resolution of the method depend on the input pulse duration, the system performance can be controlled and optimized by properly choosing the temporal duration of the interrogating pulse. A spatial resolution of 9 mm (ultimately dictated by one grating length) has been obtained with an 80 ps optical pulse, while a temperature resolution of less than 0.42 K has been demonstrated using a 500 ps incident pulse. The sensor proposed proves to be simple, robust, and polarization insensitive and alleviates the instrumentation complexity for distributed sensing applications. PMID- 26906374 TI - Photorefractive moire-like patterns for the multifringe projection method in Fourier transform profilometry. AB - In the present paper, the method of simultaneous moire-like fringe pattern projection for Fourier transform profilometry is described. The photorefractive holographic interferometric process produces controlled moire-like patterns with two or more different variation directions. Each low spatial frequency fringe pattern is experimentally obtained as a result of the superposition of two high spatial frequency sinusoidal gratings, with slightly different pitches, for each fringe variation direction. These dynamic moire-like patterns are induced due to an optical holographic beating of the sinusoidal induced gratings in the volume of the photorefractive Bi12TiO20 (BTO) crystal sample used as dynamic holographic medium. Two or more moire-like fringe patterns, with at least two different variation directions, simultaneously (or not), are projected onto the object surface. Thus, this is the 2D fringe projection stage of our proposed Fourier transform procedure to determine the profile of a simple object. PMID- 26906376 TI - Compensation method for temperature error of fiber optical gyroscope based on relevance vector machine. AB - Aiming to improve the bias stability of the fiber optical gyroscope (FOG) in an ambient temperature-change environment, a temperature-compensation method based on the relevance vector machine (RVM) under Bayesian framework is proposed and applied. Compared with other temperature models such as quadratic polynomial regression, neural network, and the support vector machine, the proposed RVM method possesses higher accuracy to explain the temperature dependence of the FOG gyro bias. Experimental results indicate that, with the proposed RVM method, the bias stability of an FOG can be apparently reduced in the whole temperature ranging from -40 degrees C to 60 degrees C. Therefore, the proposed method can effectively improve the adaptability of the FOG in a changing temperature environment. PMID- 26906377 TI - To enhance imaging performance of hybrid imaging systems by using two asymmetrical phase masks. AB - We propose the use of two asymmetrical phase masks combined with the subtracted imaging method to enhance the signal-to-noise ratio in wavefront coding systems. This subtracted imaging technique is similar to the variable pinhole diameter in confocal microscopy. Two different phase modulations of same phase masks are employed to promote the magnitude of the optical transfer function (OTF). The ratio factor is used to control the phase variation between two phase masks. The noise of decoded images is suppressed owing to the higher magnitude of the OTF than the wavefront coding systems with a phase mask. A tangent phase mask as an example is used to demonstrate our concept. Simulated results show that the performance promotion controls noise amplification of decoded images while maintaining a depth-of-field extension. PMID- 26906378 TI - Efficient 914-nm Nd:YVO4 laser under double-end polarized pumping. AB - We report herein the enhancement of output power and optical efficiency of a quasi-three-level Nd:YVO4 laser through a double-end polarized pumping scheme, which improves the usually insufficient pump absorption of the short laser gain medium with low doping concentration, and meanwhile alleviates the influence of thermal effect. 17.7 W laser output at 914 nm is obtained under the launched 808 nm pump of 53.0 W, corresponding to an optical efficiency of 33.4%. PMID- 26906379 TI - Infrared sensitive liquid crystal light valve with semiconductor substrate. AB - A liquid crystal light valve (LCLV) is an optically controlled spatial light modulator that allows recording of dynamic holograms. Almost all known LCLVs operate in the visible range of the spectrum. In the present work we demonstrate a LCLV operating in the infrared. The interaction of signal and pump waves is studied for different applied voltages, grating spacings, and intensities of the recording beams. A fourfold amplification of the weak signal beam is achieved. The amplitude of the refractive index modulation Deltan=0.007 and nonlinear coupling constant n2=-1 cm2/W are estimated from the experimental results. External phase modulation of one of the recording beams is used for a further transient increase of the signal beam gain. PMID- 26906380 TI - Full control of polarization state with a pair of electro-optic modulators for polarization-resolved optical microscopy. AB - Full and arbitrary control of polarization states of light using two independent electro-optic modulators is presented. The mechanism of the controllability is theoretically described using the Jones vector and matrix, and the polarization state change with control parameters is geometrically illustrated in the Stokes parameter space. Our theoretical framework involves possible distortions of the polarization state due to optical elements between the polarization controller and measurement point and presents a mechanism for pre-compensating the polarization distortion. The theory's validity and controllability of the polarization state are experimentally demonstrated with a test optical setup using a dichroic mirror as a polarization distorter. The inevitable intensity variation during polarization sweeps and a strategy for pre- and post compensation of the variations are discussed. The technique's applicability to bioimaging is also discussed. PMID- 26906381 TI - Optical bistability induced by spin-orbit coupling in the carbon-nanotube quantum dots. AB - We theoretically investigate steady-state behaviors of carbon nanotube quantum dots with spin-orbit coupling in a unidirectional ring cavity. Our results show that the spin-orbit coupling can induce optical bistability. In addition to the existence of spin-orbit coupling, switching optical bistability to optical multistability or vice versa is realized by adjusting detuning of the probe field. Our results show that the carbon nanotube quantum dots will possibly be a promising candidate for realizing all-optical switching. PMID- 26906382 TI - Imaging-based amplitude laser beam shaping for material processing by 2D reflectivity tuning of a spatial light modulator. AB - We have demonstrated an imaging-based amplitude laser-beam-shaping technique for material processing by 2D reflectivity tuning of a spatial light modulator. Intensity masks with 256 gray levels were designed to shape the input laser beam in the outline profile and inside intensity distribution. Squared and circular flattop beam shapes were obtained at the diffractive near-field and then reconstructed at an image plane of an f-theta lens (f~100 mm). The observed intensity distribution inside the beam-shaping geometry was much more even than using binary masks. The ablation footprint well matches the desired beam shape. PMID- 26906383 TI - Phase-shifting algorithm inside an optical cavity for absolute length measurement. AB - Phase-shifting interferometry inside an optical cavity is useful for measuring the length of a cubic object and the diameter of a metal sphere. A new error compensating phase-shifting algorithm is proposed, with which a spatially uniform phase error caused by nonlinear phase modulation can be eliminated. It is shown that the conventional algorithm design for harmonic analysis cannot compensate for this dc error unless the sampling weight definition is extended to a complex number. Specifically, a 3% quadratic nonlinearity in the phase modulation is found to yield a systematic error of 1.5 nm in the object length in many conventional algorithms. A new 13-frame algorithm is described that applies a modified discrete Fourier window and can reduce the dc error to less than 0.5 nm. PMID- 26906384 TI - Non-coaxial superposition of vector vortex beams. AB - Vector vortex beams are classified into four types depending upon spatial variation in their polarization vector. We have generated all four of these types of vector vortex beams by using a modified polarization Sagnac interferometer with a vortex lens. Further, we have studied the non-coaxial superposition of two vector vortex beams. It is observed that the superposition of two vector vortex beams with same polarization singularity leads to a beam with another kind of polarization singularity in their interaction region. The results may be of importance in ultrahigh security of the polarization-encrypted data that utilizes vector vortex beams and multiple optical trapping with non-coaxial superposition of vector vortex beams. We verified our experimental results with theory. PMID- 26906385 TI - Two spatial light modulator system for laboratory simulation of random beam propagation in random media. AB - An optical system consisting of a laser source and two independent consecutive phase-only spatial light modulators (SLMs) is shown to accurately simulate a generated random beam (first SLM) after interaction with a stationary random medium (second SLM). To illustrate the range of possibilities, a recently introduced class of random optical frames is examined on propagation in free space and several weak turbulent channels with Kolmogorov and non-Kolmogorov statistics. PMID- 26906386 TI - Holographic multi-projection using the random phase-free method. AB - We demonstrated holographic multi-projection using the random phase-free method and the iterative method. Holographic multi-projection is a method of projecting multiple different images focused on different screens at the same time. The random phase-free method succeeded in improving the image quality. By applying the iterative method to the random phase-free method, the image quality was improved further. The results of our numerical reconstruction and optical experiments confirm that the proposed method improves the image quality. The peak signal-to-noise ratios of the reconstructed images using the proposed method and the conventional method are 30.66 and 13.61 dB, respectively. PMID- 26906387 TI - Asymmetric Mach-Zehnder interferometers without an interaction window in polymer foils for refractive index sensing. AB - We report on the fabrication and characterization of integrated Mach-Zehnder interferometers in polymer foil without an interaction window. The interferometers are based on inverted rib waveguides, which allow single mode behavior even for waveguide widths larger than a few micrometers. The phase change between the two interferometer arms upon a refractive index change of the analyte that serves as the upper cladding is generated by the asymmetricity of the two interferometer arms. A difference of the waveguide width in the straight part of the interferometer leads to different effective refractive indices and thus to a change in the interference signal. We show in small scale the process chain, which is compatible with a cost-effective roll-to-roll fabrication process. For a proof of principle we apply deionized water and a glucose solution as analytes to the sensor foils and detect the transmitted intensity as a measure of the induced phase change. A detection limit of 3.10-3 refractive index units is reached for homogeneous sensing at a total system length of 9.3 mm and a total waveguide core thickness of 3 MUm. PMID- 26906388 TI - Reinjection of transmitted laser light into laser-produced plasma for efficient laser ignition. AB - For improving the laser absorption efficiency in laser ignition, the transmitted laser light was returned to the laser-produced plasma by using a corner cube. In the experiments, the transmitted light was reinjected into the plasma at different times. The laser absorption efficiency was found to be substantially improved when the transmitted light was reinjected into the plasma after adequate plasma expansion. Furthermore, through visualization experiments on gas-dynamics phenomena, it was found that the reinjection of the transmitted light affected not only the laser absorption efficiency but also the gas dynamics after breakdown, and thereby the initial flame kernel development. PMID- 26906389 TI - Modeling coverage-dependent ink thickness in ink-jet printing. AB - We propose a simple extension of the Murray-Davis halftone reflectance model that accounts for the change of ink dot reflectance due to ink spreading. Significant improvement of the prediction accuracy is obtained for a range of paper substrates and printer combinations compared to the classical Yule-Nielsen and Clapper-Yule models. The results show that ink dot thickness dependency is the main factor limiting the validity of the Murray-Davis model and that optical dot gain can be neglected when the model is calibrated for one specific printer, ink, and substrate combination. The proposed model provides a better understanding of the reflectance from halftone prints that contributes to the development of physical models for simpler and faster printer calibration to different substrates. PMID- 26906390 TI - Nonmechanical zoom lens based on the Pancharatnam phase effect. AB - We present a nonmechanical zoom lens system based on the Pancharatnam phase effect, which is controlled by the state of circularly polarized light. The device is shown to allow for a compact design for a wide range of zoom ratios. A demonstration system is shown, which has a 4* zoom ratio between its two electrically switchable states. We show its observed image quality experimentally and compare it with calculated expectations. PMID- 26906391 TI - Parametric temporal compression of infrared imagery sequences containing a slow moving point target. AB - Infrared (IR) imagery sequences are commonly used for detecting moving targets in the presence of evolving cloud clutter or background noise. This research focuses on slow-moving point targets that are less than one pixel in size, such as aircraft at long range from a sensor. Since transmitting IR imagery sequences to a base unit or storing them consumes considerable time and resources, a compression method that maintains the point target detection capabilities is highly desirable. In this work, we introduce a new parametric temporal compression that incorporates Gaussian fit and polynomial fit. We then proceed to spatial compression by spatially applying the lowest possible number of bits for representing each parameter over the parameters extracted by temporal compression, which is followed by bit encoding to achieve an end-to-end compression process of the sequence for data storage and transmission. We evaluate the proposed compression method using the variance estimation ratio score (VERS), which is a signal-to-noise ratio (SNR)-based measure for point target detection that scores each pixel and yields an SNR scores image. A high pixel score indicates that a target is suspected to traverse the pixel. From this score image we calculate the movie scores, which are found to be close to those of the original sequences. Furthermore, we present a new algorithm for automatic detection of the target tracks. This algorithm extracts the target location from the SNR scores image, which is acquired during the evaluation process, using Hough transform. This algorithm yields a similar detection probability (PD) and false alarm probability (PFA) of the compressed sequences and the original sequences. The parameters of the new parametric temporal compression successfully differentiate the targets from the background, yielding high PDs (above 83%) with low PFAs (below 0.043%) without the need to calculate pixel scores or to apply automatic detection of the target tracks. PMID- 26906392 TI - Laser frequency locking with 46 GHz offset using an electro-optic modulator for magneto-optical trapping of francium atoms. AB - We demonstrate frequency offset locking between two laser sources using a waveguide-type electro-optic modulator (EOM) with 10th-order sidebands for magneto-optical trapping of Fr atoms. The frequency locking error signal was successfully obtained by performing delayed self-homodyne detection of the beat signal between the repumping frequency and the 10th-order sideband component of the trapping light. Sweeping the trapping-light and repumping-light frequencies with keeping its frequency difference of 46 GHz was confirmed over 1 GHz by monitoring the Doppler absorption profile of I2. This technique enables us to search for a resonance frequency of magneto-optical trapping of Fr. PMID- 26906393 TI - Minimization of lumen depreciation in LED lamps using thermal transient behavior analysis and design optimizations. AB - We expansively investigate thermal behaviors of various general-purpose light emitting diode (LED) lamps and apply our measured results, validated by simulation, to establish lamp design rules for optimizing their optical and thermal properties. These design rules provide the means to minimize lumen depreciation over time by minimizing the periods for lamps to reach thermal steady-state while maintaining their high luminous efficacy and omnidirectional light distribution capability. While it is well known that minimizing the junction temperature of an LED leads to a longer lifetime and an increased lumen output, our study demonstrates, for the first time, to the best of our knowledge, that it is also important to minimize the time it takes to reach thermal equilibrium because doing so minimizes lumen depreciation and enhances light output and color stability during operation. Specifically, we have found that, in addition to inadequate heat-sink fin areas for a lamp configuration, LEDs mounted on multiple boards, as opposed to a single board, lead to longer periods for reaching thermal equilibrium contributing to larger lumen depreciation. PMID- 26906394 TI - Investigation of bend loss in single mode fibers with ultra-high-resolution photon-counting optical time domain reflectometer. AB - An intensity peak associated with fiber bending could be detected thanks to the use of an ultra-high-resolution photon-counting optical time domain reflectometer (OTDR) setup. The peak intensity is shown to be dependent on the curvature radius and angular distance of the bend. To account for such peaks, we propose a model based on modal mismatching and coupling inside the bend region and show that the model is highly consistent with the acquired data. Combining the information of the bend peak and bend loss, and taking advantage of the high dependence of the peak value with the local modal field parameter, the technique could be employed as an optical fiber local-parameter characterization method. PMID- 26906395 TI - Thermal-induced transverse-mode evolution in thermally guiding index-antiguided core fiber. AB - The transverse-mode evolution in thermally guided (TG) index-antiguided-core (IAGc) fibers is numerically studied in this paper. With the finite-element method and thermal conduction equations, the fundamental mode evolution with a thermal load is investigated, and four evolution stages (i.e., the cladding confined, quasi-cladding-confined, quasi-core-confined, and core-confined) are revealed. Thermal load thresholds corresponding to these stages are presented. Furthermore, the field evolutions of high-order modes also are investigated; the filling factors of these modes are discussed as well. The pertinent results can provide significant reference for designing TG IAGc fibers and understanding the thermal effect on the transverse mode of fibers involving the index-antiguided core. PMID- 26906396 TI - Comparison of in-laboratory and home diagnosis of sleep apnea using a cordless portable acoustic device. AB - BACKGROUND AND OBJECTIVES: Sleep apnea (SA) is a common, serious, but underdiagnosed condition. There is a need for more accessible and economic means of diagnosing SA in the home. The aim of this study was to test the validity of a cordless acoustic portable device (BresoDxTM) for home diagnosis of SA compared with standard polysomnography (PSG). METHODS: A total of 135 subjects underwent full overnight PSG and simultaneous recording of breath sounds by BresoDx in the sleep laboratory. Acoustic data extracted from BresoDx were analyzed using validated computer acoustic algorithms. The PSG-derived apnea-hypopnea index (AHI p) and the acoustic AHI (AHI-a) were calculated and compared. A subset of 100 subjects used the device in a subsequent night in their home from which home AHI (AHI-h) was determined. RESULTS: The correlation between AHI-a and simultaneous AHI-p was 95.2% and diagnostic accuracy of BresoDx ranged between 88.9% and 93.3% around AHI cutoffs of 5-15. In the home, AHI-h did not differ significantly from AHI-p (p = 0.60). Using an AHI-p cutoff >= 10 BresoDx's accuracy was 81%. Of the 100 subjects, 81 (81%) had low inter-night variability measured by a difference between home AHI-h and PSG AHI-p < 10 event/h, while 19% had higher inter-night variability. CONCLUSION: AHI determined using BresoDx was in excellent agreement with simultaneous AHI-p. The majority of patients had a consistent AHI in their subsequent home study with very good overall diagnostic accuracy. We conclude that BresoDx is a reliable device for diagnosing SA that can be used by subjects, unattended in their own homes. PMID- 26906397 TI - The addition of depression to the Framingham Risk Equation model for predicting coronary heart disease risk in women. AB - BACKGROUND: Depression is widely considered to be an independent and robust predictor of Coronary Heart Disease (CHD), however is seldom considered in the context of formal risk assessment. We assessed whether the addition of depression to the Framingham Risk Equation (FRE) improved accuracy for predicting 10-year CHD in a sample of women. DESIGN: A prospective, longitudinal design comprising an age-stratified, population-based sample of Australian women collected between 1993 and 2011 (n=862). METHODS: Clinical depressive disorder was assessed using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (SCID-I/NP), using retrospective age-of-onset data. A composite measure of CHD included non-fatal myocardial infarction, unstable angina coronary intervention or cardiac death. Cox proportional-hazards regression models were conducted and overall accuracy assessed using area under receiver operating characteristic (ROC) curve analysis. RESULTS: ROC curve analyses revealed that the addition of baseline depression status to the FRE model improved its overall accuracy (AUC:0.77, Specificity:0.70, Sensitivity:0.75) when compared to the original FRE model (AUC:0.75, Specificity:0.73, Sensitivity:0.67). However, when calibrated against the original model, the predicted number of events generated by the augmented version marginally over-estimated the true number observed. CONCLUSIONS: The addition of a depression variable to the FRE equation improves the overall accuracy of the model for predicting 10-year CHD events in women, however may over-estimate the number of events that actually occur. This model now requires validation in larger samples as it could form a new CHD risk equation for women. PMID- 26906398 TI - Two-Level Scheduling for Video Transmission over Downlink OFDMA Networks. AB - This paper presents a two-level scheduling scheme for video transmission over downlink orthogonal frequency-division multiple access (OFDMA) networks. It aims to maximize the aggregate quality of the video users subject to the playback delay and resource constraints, by exploiting the multiuser diversity and the video characteristics. The upper level schedules the transmission of video packets among multiple users based on an overall target bit-error-rate (BER), the importance level of packet and resource consumption efficiency factor. Instead, the lower level renders unequal error protection (UEP) in terms of target BER among the scheduled packets by solving a weighted sum distortion minimization problem, where each user weight reflects the total importance level of the packets that has been scheduled for that user. Frequency-selective power is then water-filled over all the assigned subcarriers in order to leverage the potential channel coding gain. Realistic simulation results demonstrate that the proposed scheme significantly outperforms the state-of-the-art scheduling scheme by up to 6.8 dB in terms of peak-signal-to-noise-ratio (PSNR). Further test evaluates the suitability of equal power allocation which is the common assumption in the literature. PMID- 26906399 TI - Host Plant Use by the Invasive Halyomorpha halys (Stal) on Woody Ornamental Trees and Shrubs. AB - The brown marmorated stink bug, Halyomorpha halys (Stal) (Hemiptera: Pentatomidae) is an invasive plant-feeding insect native to eastern Asia. This herbivore is highly polyphagous, feeding on and damaging diverse plants, including field crops, vegetables, tree fruits, and ornamentals. Woody ornamental plants provide early- and late-season resources for adults emerging from and returning to overwintering sites, as well as feeding and breeding sites for H. halys throughout the growing season. In this study, we quantify the use of diverse plants by H. halys in two commercial nurseries in Maryland, recording data on the abundance of egg masses, early and late instar nymphs, and adults over a three-year study period. Our specific goals were to provide a quantitative comparison of the use of diverse plant species and cultivated varieties, identify non-hosts that could be used to create landscapes refractory to H. halys, and determine whether the use of plants varied across life stages of H. halys or the taxonomic status of plants. We found broad use of diverse plants in this study, identifying 88 host plants used by all life stages of H. halys. We also highlight the 43 plant taxa that did not support any life stage of H. halys and are thus classified as non-hosts. Interestingly, some of these plants were congeners of highly-used plants, underscoring high intrageneric and intraspecific variation in the use of plants by this polyphagous herbivore. We discuss how the selective planting of non-hosts, especially gymnosperms, may aid in reducing the agricultural and nuisance pest status of this invasive insect. PMID- 26906400 TI - Tinnitus and cell phones: the role of electromagnetic radiofrequency radiation. PMID- 26906401 TI - Accounting for the Multiple Natures of Missing Values in Label-Free Quantitative Proteomics Data Sets to Compare Imputation Strategies. AB - Missing values are a genuine issue in label-free quantitative proteomics. Recent works have surveyed the different statistical methods to conduct imputation and have compared them on real or simulated data sets and recommended a list of missing value imputation methods for proteomics application. Although insightful, these comparisons do not account for two important facts: (i) depending on the proteomics data set, the missingness mechanism may be of different natures and (ii) each imputation method is devoted to a specific type of missingness mechanism. As a result, we believe that the question at stake is not to find the most accurate imputation method in general but instead the most appropriate one. We describe a series of comparisons that support our views: For instance, we show that a supposedly "under-performing" method (i.e., giving baseline average results), if applied at the "appropriate" time in the data-processing pipeline (before or after peptide aggregation) on a data set with the "appropriate" nature of missing values, can outperform a blindly applied, supposedly "better performing" method (i.e., the reference method from the state-of-the-art). This leads us to formulate few practical guidelines regarding the choice and the application of an imputation method in a proteomics context. PMID- 26906402 TI - [Nursing care of pulmonary embolism in out-of-hospital emergencies]. AB - Pulmonary embolism is one of the most severe venous thromboembolic diseases, both in mortality and the high number of associated complications and their impact on quality of life. The early hours are critical and proper management during this period can determine future sequels. Therefore, in the outpatient setting, nurses must have adequate knowledge and tools to act quickly and efficiently. In this paper, we present a case of a 77 year-old male in his home that after being discharged from a knee replacement surgery starts with symptoms compatible with pulmonary thromboembolism. A Nursing Care Process is performed, according to the functional patterns of Margory Gordon and a care plan is developed based on NNN taxonomy (NANDA, NOC, NIC). As main nursing diagnosis 'ineffective breathing pattern' is selected and as possible potential complication of the pulmonary embolism the 'pulmonary infarction' is chosen. The results obtained after conducting the care plan are satisfactory, improving the signs and symptoms presented by the patient, hence why we believe it is useful for nurses when facing similar clinical situations. PMID- 26906403 TI - Perspectives on seizure clusters: Gaps in lexicon, awareness, and treatment. AB - Seizure clusters in epilepsy can result in serious outcomes such as missed work or school, postictal psychosis, emergency room visits, or hospitalizations, and yet they are often not included in discussions between health-care professionals (HCPs) and their patients. The purpose of this paper was to describe and compare consumer (patient and caregivers) and professional understanding of seizure clusters and to describe how consumers and HCPs communicate regarding seizure clusters. We reviewed social media discussion sites to explore consumers' understanding of seizure clusters. We analyzed professional (medical) literature to explore the HCPs' understanding of seizure clusters. Major themes were revealed in one or both groups, including: communication about diagnosis; frequency, duration, and time frame; seizure type and pattern; severity; and self management. When comparing discussions of professionals and consumers, both consumers and clinicians discussed the definition of seizure clusters. Discussions of HCPs were understandably clinically focused, and consumer discussions reflected the experience of seizure clusters; however, both groups struggled with a common lexicon. Seizure cluster events remain a problem associated with serious outcomes. Herein, we outline the lack of a common understanding and recommend the development of a common lexicon to improve communication regarding seizure clusters. PMID- 26906404 TI - Human rhinovirus-induced inflammatory responses are inhibited by phosphatidylserine containing liposomes. AB - Human rhinovirus (HRV) infections are major contributors to the healthcare burden associated with acute exacerbations of chronic airway disease, such as chronic obstructive pulmonary disease and asthma. Cellular responses to HRV are mediated through pattern recognition receptors that may in part signal from membrane microdomains. We previously found Toll-like receptor signaling is reduced, by targeting membrane microdomains with a specific liposomal phosphatidylserine species, 1-stearoyl-2-arachidonoyl-sn-glycero-3-phospho-L-serine (SAPS). Here we explored the ability of this approach to target a clinically important pathogen. We determined the biochemical and biophysical properties and stability of SAPS liposomes and studied their ability to modulate rhinovirus-induced inflammation, measured by cytokine production, and rhinovirus replication in both immortalized and normal primary bronchial epithelial cells. SAPS liposomes rapidly partitioned throughout the plasma membrane and internal cellular membranes of epithelial cells. Uptake of liposomes did not cause cell death, but was associated with markedly reduced inflammatory responses to rhinovirus, at the expense of only modest non-significant increases in viral replication, and without impairment of interferon receptor signaling. Thus using liposomes of phosphatidylserine to target membrane microdomains is a feasible mechanism for modulating rhinovirus induced signaling, and potentially a prototypic new therapy for viral-mediated inflammation. PMID- 26906405 TI - Group 3 innate lymphoid cells regulate neutrophil migration and function in human decidua. AB - Innate lymphoid cells (ILCs) have a central role in innate defenses against pathogens, lymphoid organogenesis, and tissue remodeling. They have been detected in human decidua, however, their role in this tissue remains unclear. Successful pregnancy requires an early inflammatory phase favoring implantation and tissue remodeling as well as a subsequent regulatory phase to prevent fetal rejection and supporting neoangiogenesis. Here, we show that, during the first trimester of pregnancy, neutrophils infiltrate decidua basalis and are more abundant in normal pregnancy than in spontaneous miscarriages. Decidual neutrophils localize in proximity of NCR+ILC3, which may influence neutrophil migration and survival given their production of CXCL8 and granulocyte macrophage colony-stimulating factor (GM-CSF). Moreover, NCR+ILC3-derived GM-CSF was found to induce the expression of heparin-binding EGF-like growth factor and IL1ra in neutrophils, two proteins/cytokines involved in tissue remodeling and maintenance of pregnancy. Our data suggest that the simultaneous presence of NCR+ILC3 and neutrophils in decidual tissues and their possible cross talk, may have a role in the early phases of pregnancy. PMID- 26906407 TI - Sulfate Radical-Mediated Degradation of Sulfadiazine by CuFeO2 Rhombohedral Crystal-Catalyzed Peroxymonosulfate: Synergistic Effects and Mechanisms. AB - Copper-iron bimetallic oxides have shown great potential for powerful radical production by activating peroxides. In this work, CuFeO2 rhombohedral crystals (RCs) were synthesized and used as heterogeneous catalysts for peroxymonosulfate (PMS) activation under various conditions. Sulfadiazine, a widely used veterinary sulfonamide, was used as a target pollutant to evaluate the efficiency of this combination. The results showed that of all the catalysts tested, the CuFeO2 RCs had the greatest reactivity. Under conditions of 0.1 g L(-1) CuFeO2 RCs and 33.0 MUM PMS, the nearly complete degradation of sulfadiazine occurred within 24 min. A synergistic catalytic effect was found between solid Cu(I) and Fe(III), probably due to the accelerated reduction of Fe(III). The two activation stages that produced different radicals (hydroxyl radicals followed by sulfate radicals) existed when solid Cu(I) was used as the catalyst. The CuFeO2 RCs had a higher PMS utilization efficiency than CuFe2O4, probably because the Cu(I)-promoted reduction of solid Fe(III). A total of 10 products were identified, and their evolution was explored. On the basis of the evidence of oxidative product formation, we proposed four possible pathways of sulfadiazine degradation. PMID- 26906408 TI - Nutrition and Growth in Chronic Disease. PMID- 26906406 TI - Opioid-induced gut microbial disruption and bile dysregulation leads to gut barrier compromise and sustained systemic inflammation. AB - Morphine and its pharmacological derivatives are the most prescribed analgesics for moderate to severe pain management. However, chronic use of morphine reduces pathogen clearance and induces bacterial translocation across the gut barrier. The enteric microbiome has been shown to have a critical role in the preservation of the mucosal barrier function and metabolic homeostasis. Here, we show for the first time, using bacterial 16s rDNA sequencing, that chronic morphine treatment significantly alters the gut microbial composition and induces preferential expansion of Gram-positive pathogenic and reduction in bile-deconjugating bacterial strains. A significant reduction in both primary and secondary bile acid levels was seen in the gut, but not in the liver with morphine treatment. Morphine-induced microbial dysbiosis and gut barrier disruption was rescued by transplanting placebo-treated microbiota into morphine-treated animals, indicating that microbiome modulation could be exploited as a therapeutic strategy for patients using morphine for pain management. PMID- 26906409 TI - Interaction of Gd-DTPA with phosphate and phosphite: toward the reaction intermediate in nephrogenic systemic fibrosis. AB - Direct reactions of the MRI contrast agent K2[Gd(DTPA)(H2O)].5H2O (1) (H5DTPA = diethylenetriaminepentaacetic acid) with dipotassium hydrogen phosphate (K2HPO4) or phosphite (K2HPO3) result in the isolation of well-defined Gd-DTPA phosphite K6[Gd2(DTPA)2(HPO3)].7H2O (2) or phosphate K6[Gd2(DTPA)2(HPO4)].10H2O (3), respectively. Their lanthanum analogs K4[La2(DTPA)2(H2O)].8H2O (4), K6[La2(DTPA)2(HPO3)].7H2O (5) and K6[La2(DTPA)2(HPO4)].10H2O (6) are used for comparison. The phosphate and phosphite groups are able to substitute the coordinated water molecules in 1 and 4 in a close physiological aqueous solution, and act as bridging ligands to link adjacent Ln(DTPA)(2-) (Ln = Gd and La) into dimeric structures. Solid state and solution (13)C NMR spectra of dimer 4 show complete dissociation into its monomeric species in solution, while no dissociation is observed for lanthanum phosphite 5 and phosphate 6 in solution, which show only one set of (13)C spectra with the largest downfield shifts at 182.0 and 182.3 ppm respectively. Comparisons of the bond distances and spectral data indicate that the interaction between DTPA and central Ln(3+) cations are weakened after the substitutions, which support phosphate substituted Gd-DTPA as an initial intermediate in nephrogenic systemic fibrosis. PMID- 26906410 TI - Effects of different water management options and fertilizer supply on photosynthesis, fluorescence parameters and water use efficiency of Prunella vulgaris seedlings. AB - BACKGROUND: Prunella vulgaris L. is a medical plant cultivated in sloping, sun shaded areas in China. Recently, owing to air-environmental stress, especially drought stress strongly inhibits plant growth and development, the appropriate fertilizer supply can alleviate these effects. However, these is little information about their effects on P. vulgaris growing in arid and semi-arid areas with limited water and fertilizer supply. RESULTS: In this study, water stress decreased the photosynthetic pigment contents, inhibited photosynthetic efficiency, induced photodamage in photosystem 2 (PS2), and decreased leaf instantaneous WUE (WUEi). The decreased net photosynthetic rate (Pn) under medium drought stress compared with the control might result from stomatal limitations. However, fertilizer supply improved photosynthetic capacity by increasing the photosynthetic pigment contents and enhancing photosynthetic efficiency under water deficit. Moreover, medium fertilization also increased WUEi under the two water conditions, but fertilizer supply did little to alleviate the PS2 photodamage caused by drought stress. Hence, drought stress was the primary limitation in the photosynthetic process of P. vulgaris seedlings, while the photosynthetic characteristics of the seedlings exhibited positive responses to fertilizer supply. CONCLUSIONS: Appropriate fertilizer supply is recommended to improve photosynthetic efficiency, enhance WUEi and alleviate photodamage under drought stress. PMID- 26906411 TI - Development of Antiviral Innate Immunity During In Vitro Differentiation of Mouse Embryonic Stem Cells. AB - The innate immunity of embryonic stem cells (ESCs) has recently emerged as an important issue in ESC biology and in ESC-based regenerative medicine. We have recently reported that mouse ESCs (mESCs) do not have a functional type I interferon (IFN)-based antiviral innate immunity. They are deficient in expressing IFN in response to viral infection and have limited ability to respond to IFN. Using fibroblasts (FBs) as a cell model, the current study investigated the development of antiviral mechanisms during in vitro differentiation of mESCs. We demonstrate that mESC-differentiated FBs (mESC-FBs) share extensive similarities with naturally differentiated FBs in morphology, marker expression, and growth pattern, but their development of antiviral mechanisms lags behind. Nonetheless, the antiviral mechanisms are inducible during mESC differentiation as demonstrated by the transition of nuclear factor kappa B (NFkappaB), a key transcription factor for IFN expression, from its inactive state in mESCs to its active state in mESC-FBs and by increased responses of mESC-FBs to viral stimuli and IFN during their continued in vitro propagation. Together with our previously published study, the current data provide important insights into molecular basis for the deficiency of IFN expression in mESCs and the development of antiviral innate immunity during mESC differentiation. PMID- 26906412 TI - Transmembrane protein TMEM170A is a newly discovered regulator of ER and nuclear envelope morphogenesis in human cells. AB - The mechanism of endoplasmic reticulum (ER) morphogenesis is incompletely understood. ER tubules are shaped by the reticulons (RTNs) and DP1/Yop1p family members, but the mechanism of ER sheet formation is much less clear. Here, we characterize TMEM170A, a human transmembrane protein, which localizes in ER and nuclear envelope membranes. Silencing or overexpressing TMEM170A in HeLa K cells alters ER shape and morphology. Ultrastructural analysis reveals that downregulation of TMEM170A specifically induces tubular ER formation, whereas overexpression of TMEM170A induces ER sheet formation, indicating that TMEM170A is a newly discovered ER-sheet-promoting protein. Additionally, downregulation of TMEM170A alters nuclear shape and size, decreases the density of nuclear pore complexes (NPCs) in the nuclear envelope and causes either a reduction in inner nuclear membrane (INM) proteins or their relocalization to the ER. TMEM170A interacts with RTN4, a member of the reticulon family; simultaneous co-silencing of TMEM170A and RTN4 rescues ER, NPC and nuclear-envelope-related phenotypes, implying that the two proteins have antagonistic effects on ER membrane organization, and nuclear envelope and NPC formation. PMID- 26906413 TI - The ESCRT-II proteins are involved in shaping the sarcoplasmic reticulum in C. elegans. AB - The sarcoplasmic reticulum is a network of tubules and cisternae localized in close association with the contractile apparatus, and regulates Ca(2+)dynamics within striated muscle cell. The sarcoplasmic reticulum maintains its shape and organization despite repeated muscle cell contractions, through mechanisms which are still under investigation. The ESCRT complexes are essential to organize membrane subdomains and modify membrane topology in multiple cellular processes. Here, we report for the first time that ESCRT-II proteins play a role in the maintenance of sarcoplasmic reticulum integrity inC. elegans ESCRT-II proteins colocalize with the sarcoplasmic reticulum marker ryanodine receptor UNC-68. The localization at the sarcoplasmic reticulum of ESCRT-II and UNC-68 are mutually dependent. Furthermore, the characterization of ESCRT-II mutants revealed a fragmentation of the sarcoplasmic reticulum network, associated with an alteration of Ca(2+)dynamics. Our data provide evidence that ESCRT-II proteins are involved in sarcoplasmic reticulum shaping. PMID- 26906414 TI - Oxidized LDL induces FAK-dependent RSK signaling to drive NF-kappaB activation and VCAM-1 expression. AB - Oxidized low-density lipoprotein (oxLDL) accumulates early in atherosclerosis and promotes endothelial nuclear factor kappaB (NF-kappaB) activation, proinflammatory gene expression and monocyte adhesion. Like for other atherogenic factors, oxLDL-induced proinflammatory responses requires integrin-dependent focal adhesion kinase (FAK, also known as PTK2) signaling; however, the mechanism by which FAK mediates oxLDL-dependent NF-kappaB signaling has yet to be revealed. We now show that oxLDL induces NF-kappaB activation and VCAM-1 expression through FAK-dependent IkappaB kinase beta (IKKbeta, also known as IKBKB) activation. We further identify FAK-dependent activation of p90 ribosomal S6 kinase family proteins (RSK) as a crucial mediator of oxLDL-dependent IKKbeta and NF-kappaB signaling, as inhibiting RSK blocks oxLDL-induced IKKbeta and NF-kappaB activation, VCAM-1 expression and monocyte adhesion. Finally, transgenic mice containing a kinase-dead mutation in FAK specifically in the endothelial cells show reduced RSK activity, decreased VCAM-1 expression and reduced macrophage accumulation in regions of early atherosclerosis. Taken together, our data elucidates a new mechanism whereby oxLDL-induced endothelial FAK signaling drives an ERK-RSK pathway to activate IKKbeta and NF-kappaB signaling and proinflammatory gene expression. PMID- 26906415 TI - Mitochondrial functions of RECQL4 are required for the prevention of aerobic glycolysis-dependent cell invasion. AB - Germline mutations in RECQL4 helicase are associated with Rothmund-Thomson syndrome, which is characterized by a predisposition to cancer. RECQL4 localizes to the mitochondria, where it acts as an accessory factor during mitochondrial DNA replication. To understand the specific mitochondrial functions of RECQL4, we created isogenic cell lines, in which the mitochondrial localization of the helicase was either retained or abolished. The mitochondrial integrity was affected due to the absence of RECQL4 in mitochondria, leading to a decrease in F1F0-ATP synthase activity. In cells where RECQL4 does not localize to mitochondria, the membrane potential was decreased, whereas ROS levels increased due to the presence of high levels of catalytically inactive SOD2. Inactive SOD2 accumulated owing to diminished SIRT3 activity. Lack of the mitochondrial functions of RECQL4 led to aerobic glycolysis that, in turn, led to an increased invasive capability within these cells. Together, this study demonstrates for the first time that, owing to its mitochondrial functions, the accessory mitochondrial replication helicase RECQL4 prevents the invasive step in the neoplastic transformation process. PMID- 26906417 TI - Temporal control of bidirectional lipid-droplet motion in Drosophila depends on the ratio of kinesin-1 and its co-factor Halo. AB - During bidirectional transport, individual cargoes move continuously back and forth along microtubule tracks, yet the cargo population overall displays directed net transport. How such transport is controlled temporally is not well understood. We analyzed this issue for bidirectionally moving lipid droplets in Drosophila embryos, a system in which net transport direction is developmentally controlled. By quantifying how the droplet distribution changes as embryos develop, we characterize temporal transitions in net droplet transport and identify the crucial contribution of the previously identified, but poorly characterized, transacting regulator Halo. In particular, we find that Halo is transiently expressed; rising and falling Halo levels control the switches in global distribution. Rising Halo levels have to pass a threshold before net plus end transport is initiated. This threshold level depends on the amount of the motor kinesin-1: the more kinesin-1 is present, the more Halo is needed before net plus-end transport commences. Because Halo and kinesin-1 are present in common protein complexes, we propose that Halo acts as a rate-limiting co-factor of kinesin-1. PMID- 26906416 TI - Characterization of the mammalian family of DCN-type NEDD8 E3 ligases. AB - Cullin-RING ligases (CRL) are ubiquitin E3 enzymes that bind substrates through variable substrate receptor proteins and are activated by attachment of the ubiquitin-like protein NEDD8 to the cullin subunit. DCNs are NEDD8 E3 ligases that promote neddylation. Mammalian cells express five DCN-like (DCNL) proteins but little is known about their specific functions or interaction partners. We found that DCNLs form stable stoichiometric complexes with CAND1 and cullins that can only be neddylated in the presence of a substrate adaptor. These CAND-cullin DCNL complexes might represent 'reserve' CRLs that can be rapidly activated when needed. We further found that all DCNLs interact with most cullin subtypes, but that they are probably responsible for the neddylation of different subpopulations of any given cullin. This is consistent with the fact that the subcellular localization of DCNLs in tissue culture cells differs and that they show unique tissue-specific expression patterns in mice. Thus, the specificity between DCNL-type NEDD8 E3 enzymes and their cullin substrates is only apparent in well-defined physiological contexts and related to their subcellular distribution and restricted expression. PMID- 26906418 TI - Greatwall dephosphorylation and inactivation upon mitotic exit is triggered by PP1. AB - Entry into mitosis is induced by the activation of cyclin-B-Cdk1 and Greatwall (Gwl; also known as MASTL in mammals) kinases. Cyclin-B-Cdk1 phosphorylates mitotic substrates, whereas Gwl activation promotes the phosphorylation of the small proteins Arpp19 and ENSA. Phosphorylated Arpp19 and/or ENSA bind to and inhibit PP2A comprising the B55 subunit (PP2A-B55; B55 is also known as PPP2R2A), the phosphatase responsible for cyclin-B-Cdk1 substrate dephosphorylation, allowing the stable phosphorylation of mitotic proteins. Upon mitotic exit, cyclin-B-Cdk1 and Gwl kinases are inactivated, and mitotic substrates are dephosphorylated. Here, we have identified protein phosphatase-1 (PP1) as the phosphatase involved in the dephosphorylation of the activating site (Ser875) of Gwl. Depletion of PP1 from meioticXenopusegg extracts maintains phosphorylation of Ser875, as well as the full activity of this kinase, resulting in a block of meiotic and mitotic exit. By contrast, preventing the reactivation of PP2A-B55 through the addition of a hyperactive Gwl mutant (GwlK72M) mainly affected Gwl dephosphorylation on Thr194, resulting in partial inactivation of Gwl and in the incomplete exit from mitosis or meiosis. We also show that when PP2A-B55 is fully reactivated by depleting Arpp19, this protein phosphatase is able to dephosphorylate both activating sites, even in the absence of PP1. PMID- 26906419 TI - Ubiquitin chain diversity at a glance. AB - Ubiquitin plays an essential role in modulating protein functions, and deregulation of the ubiquitin system leads to the development of multiple human diseases. Owing to its molecular features, ubiquitin can form various homo- and heterotypic polymers on substrate proteins, thereby provoking distinct cellular responses. The concept of multifaceted ubiquitin chains encoding different functions has been substantiated in recent years. It has been established that all possible ubiquitin linkage types are utilized for chain assembly and propagation of specific signals in vivo. In addition, branched ubiquitin chains and phosphorylated ubiquitin molecules have been put under the spotlight recently. The development of novel technologies has provided detailed insights into the structure and function of previously poorly understood ubiquitin signals. In this Cell Science at a Glance article and accompanying poster, we provide an update on the complexity of ubiquitin chains and their physiological relevance. PMID- 26906420 TI - Precision autophagy directed by receptor regulators - emerging examples within the TRIM family. AB - Selective autophagy entails cooperation between target recognition and assembly of the autophagic apparatus. Target recognition is conducted by receptors that often recognize tags, such as ubiquitin and galectins, although examples of selective autophagy independent of these tags are emerging. It is less known how receptors cooperate with the upstream autophagic regulators, beyond the well characterized association of receptors with Atg8 or its homologs, such as LC3B (encoded by MAP1LC3B), on autophagic membranes. The molecular details of the emerging role in autophagy of the family of proteins called TRIMs shed light on the coordination between cargo recognition and the assembly and activation of the principal autophagy regulators. In their autophagy roles, TRIMs act both as receptors and as platforms ('receptor regulators') for the assembly of the core autophagy regulators, such as ULK1 and Beclin 1 in their activated state. As autophagic receptors, TRIMs can directly recognize endogenous or exogenous targets, obviating a need for intermediary autophagic tags, such as ubiquitin and galectins. The receptor and regulatory features embodied within the same entity allow TRIMs to govern cargo degradation in a highly exact process termed 'precision autophagy'. PMID- 26906421 TI - DICER, DROSHA and DNA damage response RNAs are necessary for the secondary recruitment of DNA damage response factors. AB - The DNA damage response (DDR) plays a central role in preserving genome integrity. Recently, we reported that the endoribonucleases DICER and DROSHA contribute to DDR activation by generating small non-coding RNAs, termed DNA damage response RNA (DDRNA), carrying the sequence of the damaged locus. It is presently unclear whether DDRNAs act by promoting the primary recognition of DNA lesions or the secondary recruitment of DDR factors into cytologically detectable foci and consequent signal amplification. Here, we demonstrate that DICER and DROSHA are dispensable for primary recruitment of the DDR sensor NBS1 to DNA damage sites. Instead, the accumulation of the DDR mediators MDC1 and 53BP1 (also known as TP53BP1), markers of secondary recruitment, is reduced in DICER- or DROSHA-inactivated cells. In addition, NBS1 (also known as NBN) primary recruitment is resistant to RNA degradation, consistent with the notion that RNA is dispensable for primary recognition of DNA lesions. We propose that DICER, DROSHA and DDRNAs act in the response to DNA damage after primary recognition of DNA lesions and, together with gammaH2AX, are essential for enabling the secondary recruitment of DDR factors and fuel the amplification of DDR signaling. PMID- 26906423 TI - Post-transcriptional regulation mediated by specific neurofilament introns in vivo. AB - Neurons regulate genes post-transcriptionally to coordinate the supply of cytoskeletal proteins, such as the medium neurofilament (NEFM), with demand for structural materials in response to extracellular cues encountered by developing axons. By using a method for evaluating functionality of cis-regulatory gene elements in vivo through plasmid injection into Xenopus embryos, we discovered that splicing of a specific nefm intron was required for robust transgene expression, regardless of promoter or cell type. Transgenes utilizing the nefm 3' UTR but substituting other nefm introns expressed little or no protein owing to defects in handling of the messenger (m)RNA as opposed to transcription or splicing. Post-transcriptional events at multiple steps, but mainly during nucleocytoplasmic export, contributed to these varied levels of protein expression. An intron of the beta-globin gene was also able to promote expression in a manner identical to that of the nefm intron, implying a more general preference for certain introns in controlling nefm expression. These results expand our knowledge of intron-mediated gene expression to encompass neurofilaments, indicating an additional layer of complexity in the control of a cytoskeletal gene needed for developing and maintaining healthy axons. PMID- 26906422 TI - The Drosophila tricellular junction protein Gliotactin regulates its own mRNA levels through BMP-mediated induction of miR-184. AB - Epithelial bicellular and tricellular junctions are essential for establishing and maintaining permeability barriers. Tricellular junctions are formed by the convergence of three bicellular junctions at the corners of neighbouring epithelia. Gliotactin, a member of the Neuroligin family, is located at theDrosophilatricellular junction, and is crucial for the formation of tricellular and septate junctions, as well as permeability barrier function. Gliotactin protein levels are tightly controlled by phosphorylation at tyrosine residues and endocytosis. Blocking endocytosis or overexpressing Gliotactin results in the spread of Gliotactin from the tricellular junction, resulting in apoptosis, delamination and migration of epithelial cells. We show that Gliotactin levels are also regulated at the mRNA level by micro (mi)RNA-mediated degradation and that miRNAs are targeted to a short region in the 3'UTR that includes a conserved miR-184 target site. miR-184 also targets a suite of septate junction proteins, including NrxIV, coracle and Mcr. miR-184 expression is triggered when Gliotactin is overexpressed, leading to activation of the BMP signalling pathway. Gliotactin specifically interferes with Dad, an inhibitory SMAD, leading to activation of the Tkv type-I receptor and activation of Mad to elevate the biogenesis and expression of miR-184. PMID- 26906424 TI - Telomerase activates transcription of cyclin D1 gene through an interaction with NOL1. AB - Telomerase is a ribonucleoprotein enzyme that is required for the maintenance of telomere repeats. Although overexpression of telomerase in normal human somatic cells is sufficient to overcome replicative senescence, the ability of telomerase to promote tumorigenesis requires additional activities that are independent of its role in telomere extension. Here, we identify proliferation-associated nucleolar antigen 120 (NOL1, also known as NOP2) as a telomerase RNA component (TERC)-binding protein that is found in association with catalytically active telomerase. Although NOL1 is highly expressed in the majority of human tumor cells, the molecular mechanism by which NOL1 contributes to tumorigenesis remained unclear. We show that NOL1 binds to the T-cell factor (TCF)-binding element of the cyclin D1 promoter and activates its transcription. Interestingly, telomerase is also recruited to the cyclin D1 promoter in a TERC-dependent manner through the interaction with NOL1, further enhancing transcription of the cyclin D1 gene. Depletion of NOL1 suppresses cyclin D1 promoter activity, thereby leading to induction of growth arrest and altered cell cycle distributions. Collectively, our findings suggest that NOL1 represents a new route by which telomerase activates transcription of cyclin D1 gene, thus maintaining cell proliferation capacity. PMID- 26906425 TI - The effects of ER morphology on synaptic structure and function in Drosophila melanogaster. AB - Hereditary spastic paraplegia (HSP) is a set of genetic diseases caused by mutations in one of 72 genes that results in age-dependent corticospinal axon degeneration accompanied by spasticity and paralysis. Two genes implicated in HSPs encode proteins that regulate endoplasmic reticulum (ER) morphology. Atlastin 1 (ATL1, also known as SPG3A) encodes an ER membrane fusion GTPase and reticulon 2 (RTN2, also known as SPG12) helps shape ER tube formation. Here, we use a new fluorescent ER marker to show that the ER within wild-type Drosophila motor nerve terminals forms a network of tubules that is fragmented and made diffuse upon loss of the atlastin 1 ortholog atl. atl or Rtnl1 loss decreases evoked transmitter release and increases arborization. Similar to other HSP proteins, Atl inhibits bone morphogenetic protein (BMP) signaling, and loss of atl causes age-dependent locomotor deficits in adults. These results demonstrate a crucial role for ER in neuronal function, and identify mechanistic links between ER morphology, neuronal function, BMP signaling and adult behavior. PMID- 26906426 TI - Familiarization Effects on Consonant Intelligibility in Dysarthric Speech. AB - BACKGROUND/AIMS: This study investigates the effects of familiarization on naive listeners' ability to identify consonants in dysarthric speech. METHODS: A total of 120 listeners (30 listeners/speaker) participated in experiments over a 6-week period. Listeners were randomly assigned to one of the three familiarization conditions: a passive condition in which listeners heard audio recordings of words, an active condition in which listeners heard audio recordings of words while viewing the written material of words, and a control condition in which listeners had no exposure to the audio signal prior to identification tasks. RESULTS: Familiarization improved naive listeners' ability to identify consonants produced by a speaker with dysarthria. The active familiarization method exhibited an advantage over the other conditions, in terms of the magnitude and rapidness of improvement. One-month delayed test scores were higher than pre familiarization scores, but the advantage of active familiarization was not present for all speakers. CONCLUSION: This study supports familiarization benefits in enhancing consonant intelligibility in dysarthria and suggests that perceptual learning mechanisms be harnessed for developing effective listener oriented intervention techniques in the management of dysarthria. Current findings call for further research on a familiarization protocol that can subserve segmental learning with maximum efficacy. PMID- 26906427 TI - Adjustable optical response of amorphous silicon nanowires integrated with thin films. AB - We experimentally demonstrate a new optical platform by integrating hydrogenated amorphous silicon nanowire arrays with thin films deposited on transparent substrates like glass. A 535 nm thick thin film is anisotropically etched to fabricate vertical nanowire arrays of 100 nm diameter arranged in a square lattice. Adjusting the nanowire length, and consequently the thin film thickness permits the optical properties of this configuration to be tuned for either transmission filter response or enhanced broadband absorption. Vivid structural colors are also achieved in reflection and transmission. The optical properties of the platform are investigated for three different etch depths. Transmission filter response is achieved for a configuration with nanowires on glass without any thin film. Alternatively, integrating thin film with nanowires increases the absorption efficiency by ~97% compared to the thin film starting layer and by ~78% over nanowires on glass. The ability to tune the optical response of this material in this fashion makes it a promising platform for high performance photovoltaics, photodetectors and sensors. PMID- 26906428 TI - Mitochondrial complex I-linked disease. AB - Complex I deficiency is the most frequently encountered single mitochondrial single enzyme deficiency in patients with a mitochondrial disorder. Although specific genotype-phenotype correlations are very difficult to identify, the majority of patients present with symptoms caused by leukodystrophy. The poor genotype-phenotype correlations can make establishing a diagnosis a challenge. The classical way to establish a complex I deficiency in patients is by performing spectrophotometric measurements of the enzyme in a muscle biopsy or other patient-derived material (liver or heart biopsy, cultured skin fibroblasts). Complex I is encoded by both the mtDNA and nuclear DNA and pathogenic mutations have been identified in the majority of the 44 genes encoding the structural subunits of complex I. In recent years, the increasing possibilities for diagnostic molecular genetic tests of large gene panels, exomes, and even entire genomes has led to the identification of many novel genetic defects causing complex I deficiency. Complex I mutations not only result in a reduced enzyme activity but also induce secondary effects at the cellular level, such as elevated reactive oxygen species production, altered membrane potential and mitochondrial morphology. At this moment there is no cure for complex I deficiency and the treatment options for complex I patients are restricted to symptomatic treatment. Recent developments, amongst others based on the treatment of the secondary effects of complex I deficiency, have shown to be promising as new therapeutic strategies in vitro and have entered clinical trials. This article is part of a Special Issue entitled Respiratory complex I, edited by Volker Zickermann and Ulrich Brandt. PMID- 26906429 TI - Glutathione reductase 2 maintains the function of photosystem II in Arabidopsis under excess light. AB - Glutathione reductase plays a crucial role in the elimination of H(2)O(2) molecules via the ascorbate-glutathione cycle. In this study, we used transgenic Arabidopsis plants with decreased glutathione reductase 2 (GR2) levels to investigate whether this GR2 activity protects the photosynthetic machinery under excess light. The transgenic plants were highly sensitive to excess light and accumulated high levels of H(2)O(2). Photosystem II (PSII) activity was significantly decreased in transgenic plants. Flash-induced fluorescence relaxation and thermoluminescence measurements demonstrated inhibition of electron transfer between Q(A) and Q(B) and decreased redox potential of Q(B) in transgenic plants. Immunoblot and blue native gel analysis showed that the levels of PSII proteins and PSII complexes were decreased in transgenic plants. Analyses of the repair of photodamaged PSII and in vivo pulse labeling of thylakoid proteins showed that the repair of photodamaged PSII is inhibited due to the inhibition of the synthesis of the D1 protein de novo in transgenic plants. Taken together, our results suggest that under excess light conditions, GR2 plays an important role in maintaining both the function of the acceptor side of PSII and the repair of photodamaged PSII by preventing the accumulation of H(2)O(2). In addition, our results provide details of the role of H(2)O(2) in vivo accumulation in photoinhibition in plants. PMID- 26906431 TI - Synthesis and characterization of POSS-(PAA)8 star copolymers and GICs for dental applications. AB - OBJECTIVE: To investigate the application of a new type of multiarm polymer resins in the formulation of Glass Ionic Cements. METHODS: A series of star copolymers of t-butyl acrylate has been prepared by ATRP using a multiarm POSS Br8 initiator. The resulting POSS-co-t-butyl acrylate star copolymers with eight arms were subsequently hydrolysed by trifluoroacetic acid to produce the corresponding POSS-co-acrylic acid star copolymers. All of the copolymers have been characterized by (1)H and (13)C NMR and FTIR spectroscopies and TGA/DSC. The as-prepared star copolymers were mixed with the glass powder from Fuji IX GP to produce the GIC samples for compression testing. RESULTS: The new type of multiarm polymer resins have been shown to have narrow molecular weight distributions and thermal properties of the acrylic acid copolymers are similar to that of poly(acrylic acid), with a two stage degradation profile involving transitions at ~140 degrees C and 250 degrees C, corresponding to anhydride formation and loss of carbon dioxide, respectively. In aqueous solution the POSS co-acrylic acid copolymers form aggregates with ~33nm dimensions. When aqueous solutions of POSS-(PAA)8 are mixed with a glass powder, a rigid glass ionomer cement, GIC, is formed with a maximum compressive stress significantly greater than that for a linear PAA GIC of a comparable polymer molecular weight. SIGNIFICANCE: Therefore, these POSS-(PAA)8 copolymers demonstrate the potential for the application of well characterized star copolymers in the future development of new GICs as dental materials. PMID- 26906432 TI - HABP2 Gene Mutations Do Not Cause Familial or Sporadic Non-Medullary Thyroid Cancer in a Highly Inbred Middle Eastern Population. AB - BACKGROUND: Familial non-medullary thyroid cancer (NMTC) occurs either as part of known hereditary syndromes or as a non-syndromic isolated hereditary tumor. Although the genes underlying the syndromic type of NMTC have been identified in most syndromes, no clear underlying gene has been identified in the non-syndromic NMTC. Recently, a c.1601G>A, p.G534E mutation in the HABP2 gene was reported to be the underlying genetic defect in a family with seven members affected by NMTC. The G534E variant has also been reported to occur in about 4.7% of cases of the Thyroid Cancer Genome Atlas (TCGA) database. OBJECTIVES: The aim of this study was to explore whether the recent finding of G534E genetic variant can be replicated in a large sample of NMTC, including 11 members of four unrelated families with familial NMTC and 509 cases of sporadic pediatric (63 cases) and adult NMTC (446 cases). METHODS: All exons and exon-intron boundaries of HABP2 were screened in 11 members of four families with familial non-syndromic NMTC using DNA isolated from peripheral leucocytes, polymerase chain reaction, and direct sequencing. The G534E variant was also screened for specifically in 229 cases of sporadic NMTC using DNA isolated from peripheral leucocytes and an additional 217 cases of NMTC using DNA isolated from formalin-fixed paraffin embedded tumor tissues. As a control cohort, 190 healthy individuals without known thyroid disease were also studied for the presence of the G534E variant using DNA isolated from peripheral leucocytes. RESULTS: None of the familial NMTC carried HABP2 mutations. Of 509 sporadic NMTC, only one case (0.2%) harbored the G534E variant. Similarly, only one case (0.5%) of the control group harbored the G534E variant. CONCLUSION: In this study, HABP2 mutations were not found in familial NMTC, and the G534E variant is not the underlying genetic defect in a large sample of sporadic NMTC from the Middle East. PMID- 26906430 TI - Regulation of V-ATPase assembly and function of V-ATPases in tumor cell invasiveness. AB - V-ATPases are ATP-driven proton pumps that function within both intracellular compartments and the plasma membrane in a wide array of normal physiological and pathophysiological processes. V-ATPases are composed of a peripheral V(1) domain that hydrolyzes ATP and an integral V(0) domain that transports protons. Regulated assembly of the V-ATPase represents an important mechanism of regulating V-ATPase activity in response to a number of environmental cues. Our laboratory has demonstrated that glucose-dependent assembly of the V-ATPase complex in yeast is controlled by the Ras/cAMP/PKA pathway. By contrast, increased assembly of the V-ATPase during dendritic cell maturation involves the PI-3 kinase and mTORC1 pathways. Recently, we have shown that amino acids regulate V-ATPase assembly in mammalian cells, possibly as a means to maintain adequate levels of amino acids upon nutrient starvation. V-ATPases have also been implicated in cancer cell survival and invasion. V-ATPases are targeted to different cellular membranes by isoforms of subunit a, with a3 targeting V ATPases to the plasma membrane of osteoclasts. We have shown that highly invasive human breast cancer cell lines express higher levels of the a3 isoform than poorly invasive lines and that knockdown of a3 reduces both expression of V ATPases at the plasma membrane and in vitro invasion of breast tumor cells. Moreover, overexpression of a3 in a non-invasive breast epithelial line increases both plasma membrane V-ATPases and in vitro invasion. Finally, specific ablation of plasma membrane V-ATPases in highly invasive human breast cancer cells using either an antibody or small molecule approach inhibits both in vitro invasion and migration. These results suggest that plasma membrane and a3-containing V-ATPases represent a novel and important target in the development of therapeutics to limit breast cancer metastasis. This article is part of a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2 6, 2016', edited by Prof. Paolo Bernardi. PMID- 26906433 TI - Lactobacillus plantarum NCU116 attenuates cyclophosphamide-induced intestinal mucosal injury, metabolism and intestinal microbiota disorders in mice. AB - Anticancer drugs at high doses often damage the intestinal mucosa and metabolism. Lactobacillus plantarum NCU116 (NCU116) isolated from pickled vegetables was orally given to cyclophosphamide-treated mice to determine its effects on intestinal mucosal injury, nutrient metabolism and colon microbiota, and investigate the mechanisms accounting for its effects. Mice treated with the bacterium were found to favorably recover intestine morphology of villus height and crypt depth, and have improved mucins expression and quantity of goblet cells, as well as intestinal metabolism by increasing the level of short-chain fatty acids and reducing the concentration of ammonia in the colon feces. In addition, NCU116-treated mice showed a higher diversity of colonic microbiota than the group without bacterium supplementation. The number of Lactobacillus and Bifidobacterium in the mouse colon was increased after bacterium intake, which decreased the number of potentially pathogenic bacteria, Escherichia coli and Pseudomonas. These results indicated that NCU116 could be of significant advantage in reducing intestinal mucosal injury and improving the intestinal metabolism and the intestinal microbiota. PMID- 26906434 TI - Functionalization of cubic mesoporous silica SBA-16 with carboxylic acid via one pot synthesis route for effective removal of cationic dyes. AB - In this work, we demonstrate that a high density of -COOH groups loading, up to 60 mol% based on silica, is successfully incorporated into SBA-16 via a one-pot synthesis route, which involves co-condensation of carboxyethylsilanetriol sodium salt (CES) and tetraethylorthosilicate (TEOS) templated by Pluronic F127 and P123 in an acidic medium. A variety of characterization techniques are performed to confirm quantitative incorporation of carboxylic groups into ordered cubic mesostructures. These functionalized materials are used to effectively remove two cationic dyes methylene blue (MB) and phenosafranine (PF) with the maximum adsorption capacities of 561 and 519 mg g(-1), respectively, at pH 9. The zeta potential results reveal that the electrostatic interactions between cationic dye molecule and negatively charged surface of the adsorbent play a crucial role in their high adsorption capacities. For a binary component system consisting of MB and PF, competitive adsorption of these two dyes is observed with adsorption capacity values slightly lower than those of the corresponding single dye systems. The dye adsorbed material can be easily regenerated by simple acid washing and be reused for five times with MB removal efficiency still up to 98.6%, showing its great potentials in environmental remediation. PMID- 26906435 TI - A novel elemental sulfur-based mixotrophic denitrifying membrane bioreactor for simultaneous Cr(VI) and nitrate reduction. AB - This study aims at investigating the simultaneous nitrate and chromate reduction by combining the advantages of sulfur-based autotrophic denitrification, heterotrophic denitrification and membrane bioreactor (MBR) technologies. A laboratory-scale MBR equipped with hydrophilic flat sheet polyethersulfone (PES) membranes (0.45MUm) was used to evaluate the performance of mixotrophic denitrification at varying nitrate and Cr(VI) concentrations. Methanol was supplied at C/N (mg methanol/mg NO3--N) ratio of 1.33. In the absence of Cr(VI), almost complete denitrification of 50mg/L NO3--N was obtained and the methanol requirement (3.60+/-0.9mg COD/(mg NO3--N)) for heterotrophic denitrifiers, was quite close to the theoretical value (3.7mg COD/(mg NO3--N)). Around 54% of the influent nitrate was denitrified by heterotrophs and the rest (56%) was denitrified by autotrophic sulfur oxidizers. The effluent sulfate averaged around 200mg/L, which was below than the theoretical sulfate concentration if autotrophic denitrification process was used alone. Autotrophic denitrification activity completely ceased at 5mg/L Cr(VI), but heterotrophic denitrification did not show any inhibition. Almost complete chromate and nitrate reduction was observed at 1mg/L Cr(VI). MBR was operated for around 200days and a weekly physical membrane cleaning was enough at a flux of 15 LMH. PMID- 26906436 TI - Physician health and wellbeing provide challenges to patient safety and outcome quality across the careerspan. AB - OBJECTIVE: Age correlated changes in mental and physical capacity have contributed to increasing concerns about older physicians' clinical competence. This paper explores the relationship between age and health in a clinical population referred for fitness for duty evaluations. METHODS: Fifty cases from an evaluation center performing fitness for duty evaluations were randomly selected. Cases were reviewed for referral reason, demographic information, diagnosis, and recommendations. RESULTS: Age ranged from 28-70 (median age of 51, mode of 45).Eighty-eight percent of cases had a diagnosed medical condition with potential cognitive sequellae. CONCLUSION: While the literature supports performance concerns in aging practitioners, health independent of age, appears to be an important contributing factor. A screening process considering biopsychosocial reserve and professional load while applicable to older clinicians would optimally be implemented for physicians across their careerspan. PMID- 26906437 TI - Aripiprazole long-acting injection: promising but more evidence needed. AB - OBJECTIVE: Aripiprazole long acting injection (ALAI) is now available, and this paper aims to assist clinicians in deciding when to use ALAI. CONCLUSION: Aripiprazole is a partial dopamine agonist with low sedation, relatively favourable metabolic profile and a tendency to lower, rather than raise, prolactin. Available for over a decade, aripiprazole has been increasingly recognised by many clinicians as a useful option in the treatment of psychoses. ALAI is a suspension of crystalline aripiprazole in water which takes 5-7 days to reach steady state after an initial intramuscular injection. Monthly injections achieve steady state in four months. Studies have demonstrated that ALAI is effective in aripiprazole-responsive patients. ALAI was generally well tolerated, but more prone to cause extrapyramidal side-effects than the oral form. ALAI has not been compared with other depots. Although the recommended starting dose is 400 mg, it is likely that there will be significant inter-individual dose variation. Dose optimisation in each patient will be necessary for best effectiveness and tolerability. ALAI is currently appropriate for aripiprazole responsive patients who need a depot, but clinicians are likely to try ALAI in patients who have been on other depots, particularly in whom weight gain and hyperprolactinaemia have been problematic. PMID- 26906438 TI - Psychiatrist-determined suitability of patients on long-acting injectable antipsychotics to be discharged from specialist to primary care. AB - OBJECTIVE: We aim to determine psychiatrists' identified factors associated with suitability of discharging patients on long-acting injectable antipsychotics (LAI) from specialist to primary care. METHOD: We undertook a retrospective observational study utilising case file reviews. A questionnaire was developed specifically for this including sociodemographic information, clinical characteristics of the patients and clinical opinion on suitability of discharge to primary care. RESULTS: In total, 72 case files (51 men, 21 women) were included in the study. The most common diagnosis was schizophrenia (71%) and Risperidone was the most often used LAI (71%). Fourteen (19%) of the patients were deemed suitable for discharge to primary care. A minimum period of 1 year of stability, having good cognitive function and insight, and absence of high-risk history were associated with suitability for discharge. CONCLUSIONS: Treating psychiatrists consider only a minority of patients on long-acting injection antipsychotics as suitable for discharge to primary care. PMID- 26906439 TI - A retrospective chart audit of electroconvulsive therapy at a regional Australian hospital. AB - OBJECTIVES: The objective of the current study was to provide a contemporary review of electroconvulsive therapy (ECT) practice in Far North Queensland, Australia. METHOD: Demographic, diagnostic and treatment characteristics were extracted from the hospital files of people who received ECT between 2011 and 2013. Data were quantitatively analysed and described. RESULTS: Depressive illnesses were the most common indicator for treatment. However, psychotic illnesses also made up a large proportion of treated cases. The technical aspects of treatment were commensurate with previous Australian findings except for the higher incidence of bifrontal ECT and maintenance treatment. CONCLUSIONS: Further research is needed across Australia to determine whether the findings of the current study represent changes in Australian ECT practice. PMID- 26906440 TI - Later life transitions and changes in psychiatry. AB - OBJECTIVE: The objective of this study was to discuss some concerns that today's psychiatrists are likely to experience in the later stages of their careers. CONCLUSIONS: When changes associated with ageing begin to make their presence felt, there is a need to come to terms with them. For many psychiatrists this may generate a surprising creativity. Psychiatrists also need to come to terms with a paradigm change that has taken place in psychiatric practice. This paper, one of a series that captures a broad perspective on ageing, was solicited (by the Members Engagement Committee) to specifically capture the psychotherapist's view of later life transitions. PMID- 26906441 TI - Correlates of rehospitalisation in schizophrenia. AB - OBJECTIVES: Schizophrenia typically has a fluctuating course; rehospitalisation is common. We studied associations between discharge variables and subsequent two year rehospitalisation rates. METHOD: Using a New Zealand national database, we obtained rehospitalisation rates and bed days for 451 patients with schizophrenia discharged from three inpatient facilities between July 2009 and December 2011. RESULTS: Nearly half (44%) of the cohort were rehospitalised within two years. Patients over 50 were less likely [hazard ratio (HR) = 0.58, 95% confidence interval (CI) = 0.35-0.97, p = 0.04] to be rehospitalised. Patients whose index admission included compulsory treatment appeared more likely (HR = 1.3, 95% CI = 0.98-1.71, p = 0.06) to be rehospitalised and spent longer rehospitalised (p = 0.05). Those whose index admission was three weeks or longer were less likely (HR = 0.53, 95% CI = 0.39-0.72, p = 0.001) to be rehospitalised. Antipsychotic types, routes and dosages were not significantly associated with rehospitalisation rate, except for those prescribed clozapine (HR = 0.61, 95% CI = 0.41-0.89, p = 0.01). CONCLUSIONS: Rehospitalisation rates were higher for patients under the age of 50 and those with shorter index admissions; the latter finding requires further study. Other than the beneficial effect of clozapine, the type and route of prescribed antipsychotics did not significantly affect rehospitalisation rates. PMID- 26906442 TI - Medical student teaching in the private sector - An overlooked opportunity? AB - OBJECTIVE: One in four psychiatric beds in Australia are located in the private sector, and more than half of Australian psychiatrists undertake private work. However, nearly all medical student teaching in psychiatry takes place in public hospitals. This paper explores the learning opportunities in the private sector. We report the South Australian experience; medical students have been taught in Ramsay Health Care (SA) Mental Health facilities for more than 23 years. CONCLUSIONS: Our experience demonstrates that clinical teaching in private hospitals is sustainable and well accepted by students, patients and clinicians. The private sector has the capacity to make a much greater contribution to medical student training in psychiatry. PMID- 26906443 TI - Expert leadership of eating disorder services in South Australia. AB - OBJECTIVES: The objective of this study was to describe the history of South Australian Government eating disorder service from the perspective of changing leadership, health policies and politics. CONCLUSIONS: The history reveals a foundation of early expert academic clinical leadership changing into a centralised managerial bureaucracy correlating with a diminution of services. A threat to the survival of the service led to a solution involving reinvigoration of expert clinical and academic leadership. Expert leadership was shown to be an important part of an eating disorder service. PMID- 26906444 TI - Biodiesel production from different algal oil using immobilized pure lipase and tailor made rPichia pastoris with Cal A and Cal B genes. AB - In this investigation, oil extraction was performed in marine macroalgae Gracilaria edulis, Enteromorpha compressa and Ulva lactuca. The algal biomass was characterized by Scanning Electron Microscopy and Fourier Transform-Infra Red Spectroscopy. Six different pre-treatment methods were carried out to evaluate the best method for maximum oil extraction. Optimization of extraction parameters were performed and high oil yield was obtained at temperature 55 degrees C, time 150min, particle size 0.10mm, solvent-to-solid ratio 6:1 and agitation rate 500rpm. After optimization, 9.5%, 12.18% and 10.50 (g/g) of oil extraction yield was achieved from the respective algal biomass. The rate constant for extraction was obtained as first order kinetics, by differential method. Stable intracellular Cal A and Cal B lipase producing recombinant Pichia pastoris was constructed and used as biocatalyst for biodiesel production. Comparative analysis of lipase activity and biodiesel yield was made with immobilized Candida antarctica lipase. PMID- 26906445 TI - Study of optimization of wastewater contaminant removal along with extracellular polymeric substances (EPS) production by a thermotolerant Bacillus sp. ISTVK1 isolated from heat shocked sewage sludge. AB - The present work involved study of wastewater contaminant removal along with EPS production by a thermotolerant bacterium Bacillus sp. ISTVK1, isolated from heat shocked sewage sludge. EPS production in basal and mineral medium containing 50% filter sterilized wastewater and 0.5% sucrose was found to be 0.83+/-0.12gL(-1) and 0.31+/-0.10gL(-1) culture, respectively. GC-MS analysis of EPS revealed the presence of beta-d-glucose, alpha-d-galactose and beta-d-arabinose. FT-IR spectrum confirmed the presence carbohydrates. Box-Behnken design was used to optimize process parameters for enhanced EPS production along with % COD reduction of wastewater. The optimised conditions when used in a 1.5L bioreactor showed EPS production of 1.67+/-0.06gL(-1) culture and 93.0+/-0.21 % COD removal. PMID- 26906446 TI - Microbial fuel cells as pollutant treatment units: Research updates. AB - Microbial fuel cells (MFC) are a device that can convert chemical energy in influent substances to electricity via biological pathways. Based on the consent that MFC technology should be applied as a waste/wastewater treatment unit rather than a renewable energy source, this mini-review discussed recent R&D efforts on MFC technologies for pollutant treatments and highlighted the challenges and research and development needs. Owing to the low power density levels achievable by larger-scale MFC, the MFC should be used as a device other than energy source such as being a pollutant treatment unit. PMID- 26906447 TI - Cloning, characterization and expression of a novel haplotype cry2A-type gene from Bacillus thuringiensis strain SWK1, native to Himalayan valley Kashmir. AB - Bacillus thuringiensis (Bt) is a gram positive bacterium which is effectively being used in pest management strategies as an eco-friendly bioinsecticide. In the present study a new cry2A gene was cloned from a promising indigenous B. thuringiensis SWK1 strain previously characterized for its toxicity against Spodoptera litura and Helicoverpa armigera larvae. The nucleotide sequence of the cloned cry2A gene pointed out that the open reading frame has 1902 bases encoding a polypeptide of 634 amino acid residues with a probable molecular weight of 70kDa. Homology comparisons showed that the deduced amino acid sequence of Cry2A had a similarity of 94% compared to that of the known Cry2Aa protein in the NCBI database and this gene has been named as cry2Al1 by the B. thuringiensis delta endotoxin Nomenclature Committee. cry2Al1 was ligated into pET 22b vector and expressed in Escherichia coli BL21 (DE3) pLysS under the control of T7 promoter induced by isopropyl-beta-d-thiogalactopyranoside (IPTG). SDS-PAGE analysis confirmed the expression of cry2Al1 as ~65kDa protein. Insect pest bioassays with neonate larvae of S. litura and H. armigera showed that the purified Cry2Al1 are toxic to S. litura and H. armigera with LC50 2.448MUg/ml and H. armigera with 3.374MUg/ml respectively. PMID- 26906449 TI - Revisiting the mechanism of redox-polymerization to build the hydrogel with excellent properties using a novel initiator. AB - In this paper, polyetheramine, a kind of linear epoxy polymer, has been used as both an initiator and a cross-linker for the synthesis of polyacrylamide hydrogel by means of a one pot method, which is a simple, time saving, facile and easily controlled process and the obtained hydrogel showed super stretchable and highly elastic properties. More impressively, only very low content of polyetheramine (0.1 wt%) could exhibit greatly enhanced mechanical properties toward polyacrylamide and the properties of hydrogel could be easily tailored by the weight ratio of polyetheramine to acrylamide. These hydrogels could be stretched up to 2000% with a maximal fracture energy up to 3.2 MJ m(-3). These types of hydrogels could be recovered immediately with low residual strains upon unloading even after 1000% strain. The presence of polyetheramine could create a more homogeneous distribution of crosslinking points and can dissipate the energy effectively, which can be responsible for the improved mechanical properties. PMID- 26906448 TI - A behavior change program to increase outings delivered during therapy to stroke survivors by community rehabilitation teams: The Out-and-About trial. AB - BACKGROUND: Australian guidelines recommend that outdoor mobility be addressed to increase participation after stroke. AIM: To investigate the efficacy of the Out and-About program at increasing outings delivered during therapy by community teams, and outings taken by stroke survivors in real life. METHOD: Cluster randomized trial involving 22 community teams providing stroke rehabilitation. Experimental teams received the Out-and-About program (a behavior change program comprising a training workshop with barrier identification and booster session, printed educational materials, audit, and feedback). Control teams received printed clinical guidelines only. The primary outcome was the percentage of stroke survivors receiving four or more outings during therapy. Secondary outcomes included the number of outings received by stroke survivors during therapy and undertaken in real life. RESULTS: At 12 months after implementation of the behavior change program, 9% of audited experimental group stroke survivors received four or more outings during therapy compared with 5% in the control group (adjusted risk difference 4%, 95% CI - 9 to 17, p = 0.54). They received 1.1 (SD 0.9) outings during therapy compared with 0.6 (SD 1.0) in the control group (adjusted mean difference 0.5, 95% CI - 0.4 to 1.4; p = 0.26). After six months of rehabilitation, observed experimental group stroke survivors took 9.0 (SD 3.0) outings per week in real life compared with 7.4 (SD 4.0) in the control group (adjusted mean difference 0.5, 95% CI - 1.8 to 2.8; p = 0.63). CONCLUSION: The Out-and-About program did not change team or stroke survivor behavior. PMID- 26906450 TI - Expanding the library of divalent fucosidase inhibitors with polyamino and triazole-benzyl bridged bispyrrolidines. AB - A small library of divalent fucosidase inhibitors containing pyrrolidine motifs and separated by polyamino and triazole-benzylated spacers was prepared and evaluated as alpha-fucosidase inhibitors. Although a weak multivalent effect was observed in polyamino derived dimers, useful structural information can be deduced about the length of the bridge, the number of nitrogen atoms present and the moieties close to the pyrrolidine. Within these investigations one of the best alpha-fucosidase inhibitors containing a pyrrolidine framework was obtained (18, Ki = 3.7 nM). PMID- 26906451 TI - Use of cinacalcet for the management of hyperparathyroidism in patients with different degrees of renal failure. AB - BACKGROUND: The effects of cinacalcet in persistent and/or hypercalcaemia associated secondary hyperparathyroidism (SHPT) have been described in patients on dialysis. OBJECTIVES: To evaluate the efficacy and safety of cinacalcet in SHPT not on dialysis and its effects on bone turnover markers. METHODS: Non randomised, longitudinal, observational, analytical study of patients with chronic kidney disease (CKD) and SHPT (PTH> 80 pg/mL) as well as normo- or hypercalcaemia (>=8.5mg/dL), treated with cinacalcet. RESULTS: Mean cinacalcet dose was 30mg/day in 66.7%. We studied 15 patients (10 women), aged 66.0+/ 17.93years. The aetiology was unknown in 20% of cases. Sociodemographic variables and renal function parameters were recorded. We compared values at baseline as well as after 6 and 12 months. Calcium (10.3+/-0.55 vs. 9.4+/-1.04) and iPTH (392.4+/-317.65 vs. 141.8+/-59.26) levels decreased. Increased levels of phosphorus (3.7+/-1.06 vs. 3.9+/-0.85) and beta-CTX (884.2+/-797.22 vs. 1053.6+/ 999.00) were detected, although there were no significant changes in GFR, urinary calcium or other bone markers. Two patients withdrew from the study (gastrointestinal intolerance and parathyroidectomy, respectively). CONCLUSIONS: Cinacalcet at low doses is effective in the management of SHPT in CKD patients who are not on dialysis. Its use reduces iPTH and calcaemia, without causing serious side effects or significant changes in renal function. PMID- 26906452 TI - Unique Loss of the PYHIN Gene Family in Bats Amongst Mammals: Implications for Inflammasome Sensing. AB - Recent genomic analysis of two bat species (Pteropus alecto and Myotis davidii) revealed the absence of the PYHIN gene family. This family is recognized as important immune sensors of intracellular self and foreign DNA and activators of the inflammasome and/or interferon pathways. Further assessment of a wider range of bat genomes was necessary to determine if this is a universal pattern for this large mammalian group. Here we expanded genomic analysis of this gene family to include ten bat species. We confirmed the complete loss of this gene family, with only a truncated AIM2 remaining in one species (Pteronotus parnellii). Divergence of the PYHIN gene loci between the bat lineages infers different loss-of-function histories during bat evolution. While all other major groups of placental mammals have at least one gene member, only bats have lost the entire family. This removal of inflammasome DNA sensors may indicate an important adaptation that is flight-induced and related, at least in part, to pathogen-host co-existence. PMID- 26906454 TI - High-Density Liquid-State Machine Circuitry for Time-Series Forecasting. AB - Spiking neural networks (SNN) are the last neural network generation that try to mimic the real behavior of biological neurons. Although most research in this area is done through software applications, it is in hardware implementations in which the intrinsic parallelism of these computing systems are more efficiently exploited. Liquid state machines (LSM) have arisen as a strategic technique to implement recurrent designs of SNN with a simple learning methodology. In this work, we show a new low-cost methodology to implement high-density LSM by using Boolean gates. The proposed method is based on the use of probabilistic computing concepts to reduce hardware requirements, thus considerably increasing the neuron count per chip. The result is a highly functional system that is applied to high speed time series forecasting. PMID- 26906455 TI - Superlinear Summation of Information in Premotor Neuron Pairs. AB - Whether premotor/motor neurons encode information in terms of spiking frequency or by their relative time of firing, which may display synchronization, is still undetermined. To address this issue, we used an information theory approach to analyze neuronal responses recorded in the premotor (area F5) and primary motor (area F1) cortices of macaque monkeys under four different conditions of visual feedback during hand grasping. To evaluate the sensitivity of spike timing correlation between single neurons, we investigated the stimulus dependent synchronization in our population of pairs. We first investigated the degree of correlation of trial-to-trial fluctuations in response strength between neighboring neurons for each condition, and second estimated the stimulus dependent synchronization by means of an information theoretical approach. We compared the information conveyed by pairs of simultaneously recorded neurons with the sum of information provided by the respective individual cells. The information transmission across pairs of cells in the primary motor cortex seems largely independent, whereas information transmission across pairs of premotor neurons is summed superlinearly. The brain could take advantage of both the accuracy provided by the independency of F1 and the synergy allowed by the superlinear information population coding in F5, distinguishing thus the generalizing role of F5. PMID- 26906456 TI - Programming Light-Harvesting Efficiency Using DNA Origami. AB - The remarkable performance and quantum efficiency of biological light-harvesting complexes has prompted a multidisciplinary interest in engineering biologically inspired antenna systems as a possible route to novel solar cell technologies. Key to the effectiveness of biological "nanomachines" in light capture and energy transport is their highly ordered nanoscale architecture of photoactive molecules. Recently, DNA origami has emerged as a powerful tool for organizing multiple chromophores with base-pair accuracy and full geometric freedom. Here, we present a programmable antenna array on a DNA origami platform that enables the implementation of rationally designed antenna structures. We systematically analyze the light-harvesting efficiency with respect to number of donors and interdye distances of a ring-like antenna using ensemble and single-molecule fluorescence spectroscopy and detailed Forster modeling. This comprehensive study demonstrates exquisite and reliable structural control over multichromophoric geometries and points to DNA origami as highly versatile platform for testing design concepts in artificial light-harvesting networks. PMID- 26906457 TI - Medicines administration for residents with dysphagia in care homes: A small scale observational study to improve practice. AB - BACKGROUND: In the UK, 69.5% of residents in care homes are exposed to one or more medication errors and 50% have some form of dysphagia. Hospital research identified that nurses frequently crush tablets to facilitate swallowing but this has not been explored in care homes. This project aimed to observe the administration of medicines to patients with dysphagia (PWD) and without in care homes. METHOD: A convenient sample of general practitioners in North Yorkshire invited care homes with nursing, to participate in the study. A pharmacist specialised in dysphagia observed nurses during drug rounds and compared these practices with national guidelines. Deviations were classified as types of medication administration errors (MAEs). RESULTS: Overall, 738 administrations were observed from 166 patients of which 38 patients (22.9%) had dysphagia. MAE rates were 57.3% and 30.8% for PWD and those without respectively (p<0.001). PWD were more likely to experience inappropriate prescribing (IP). Signs of aspiration were more frequently observed in PWD when IP occurred (p<0.001). CONCLUSION: Observation of medication administration practices by independent pharmacists may enable the identification of potentially dangerous practices and be used as a method of staff support. Unidentified signs of aspiration suggest that nurses require training in dysphagia and need to communicate its presence to the resident's GP. Further research should explore the design of an effective training for nurses. PMID- 26906458 TI - Application of in vitro transmucosal permeability, dose number, and maximum absorbable dose for biopharmaceutics assessment during early drug development for intraoral delivery. AB - Intraoral (IO) administration is a unique route that takes advantage of transmucosal absorption in the oral cavity to deliver a drug substance locally or systemically. IO delivery can also enhance or enable oral administration, providing a better therapeutic benefit/safety risk profile for patient compliance. However, there are relatively few systematic biopharmaceutics assessments for IO delivery to date. Therefore, the goals of this study were to i) identify the most relevant in vitro permeability models as alternatives to porcine oral tissues (gold standard) for predicting human IO absorption and ii) establish guidelines for biopharmaceutics assessment during early drug development for IO delivery. Porcine kidney LLC-PK1 cells provided the strongest correlation of transmucosal permeability with porcine oral tissues followed by human Caco-2 cells. Furthermore, cultured human buccal tissues predicted high/low permeability classification and correlated well with porcine oral tissues, which are used for predicting clinical IO absorption. In the meantime, we introduced maximum absorbable dose and dose number in the oral cavity for IO delivery assessment as well as a decision tree to provide guidance for biopharmaceutics assessment during early drug development for IO delivery. PMID- 26906459 TI - A facile Friedel-Crafts acylation for the synthesis of polyethylenimine-grafted multi-walled carbon nanotubes as efficient gene delivery vectors. AB - Low chemical reactivity of carbon nanotubes is one of the major obstacles in their functionalization via chemical reactions. As a non-destructive method, Friedel-Crafts acylation was suggested among the explored reactions for which only a few methods have been reported under harsh reaction conditions, e.g., high temperature all leading to low yields. In this study, we propose a novel method for the acylation of multi-walled carbon nanotubes (MWCNTs) at a low temperature (i.e., 42 degrees C), using SiO2-Al2O3 as a catalyst and 6-bromohexanoic acid as the acylating agent to produce high yield functionalized MWCNTs. After acylation, MWCNTs are conjugated with polyethylenimines (PEIs) with three molecular weights (1.8, 10 and 25kDa). Three different MWCNT-PEI conjugates are synthesized and evaluated for their condensation ability, viability, size and zeta potential properties. The transfection efficiency of the functionalized MWCNTs is evaluated using luciferase assay and flow cytometry in a Neuroblastoma cell line. MWCNT-PEI (10 kDa) conjugate shows the highest transfection efficacy compared to others. For this carrier transfection efficacy exceeds the amount of PEI 25 kDa at similar carrier to plasmid weight ratio (C/P) and is around 3 times higher compared to PEI 25 kDa at C/P=0.8 as positive control regarding its high transfection efficiency and low cytotoxicity. PMID- 26906460 TI - Meniscal Allograft Transplantation in the Adolescent Population. AB - PURPOSE: To report the results of meniscal allograft transplantation (MAT) with minimum 2-year follow-up in an active adolescent population. METHODS: After institutional review board approval, all patients aged 16 years or younger who underwent MAT and had more than 2 years' clinical follow-up were identified from a prospectively collected database. Demographic data were collected and summary statistics calculated. Functional outcome scores were collected preoperatively and at 6 months, 1 year, 2 years, and final follow-up. Differences between scores at each time point were calculated using a mixed-model repeated-measures analysis of variance. All prior procedures and reoperations were documented. RESULTS: Thirty-seven MAT procedures were performed in 36 children (84% lateral and 16% medial). For 32 of these procedures (86%), the patients met the inclusion criteria with minimum 2-year follow-up. The mean age was 15.4 +/- 1.04 years (range, 13 to 16 years). All patients had undergone prior knee surgery. Of the 32 patients, 23 (72%) were girls and 9 (28%) were boys. Eleven patients had open physes. Forty-eight percent of patients underwent concomitant procedures, mainly for chondral defects. The mean length of clinical follow-up was 7.2 +/- 3.2 years (range, 2 to 15 years). MAT resulted in significant improvements in the Knee Injury and Osteoarthritis Outcome Score, Lysholm score, International Knee Documentation Committee subjective score, Western Ontario and McMaster Universities Osteoarthritis Index pain score, Western Ontario and McMaster Universities Osteoarthritis Index function score, and Short Form 12 physical score. After MAT, 7 patients (22%) underwent 8 surgical procedures, most of which were for chondral disease. The meniscal reoperation rate was 6%. No revision MAT procedures were required. No angular deformities or limb-length inequalities were reported. CONCLUSIONS: MAT resulted in predictable improvements in functional outcomes in the adolescent population. The meniscal reoperation rate was low (6%), no revision MAT procedures were required, and no growth complications were reported. Chondral disease remains the primary reason for reoperation after MAT. LEVEL OF EVIDENCE: Level IV, therapeutic case series. PMID- 26906453 TI - PP2A as a master regulator of the cell cycle. AB - Protein phosphatase 2A (PP2A) plays a critical multi-faceted role in the regulation of the cell cycle. It is known to dephosphorylate over 300 substrates involved in the cell cycle, regulating almost all major pathways and cell cycle checkpoints. PP2A is involved in such diverse processes by the formation of structurally distinct families of holoenzymes, which are regulated spatially and temporally by specific regulators. Here, we review the involvement of PP2A in the regulation of three cell signaling pathways: wnt, mTOR and MAP kinase, as well as the G1->S transition, DNA synthesis and mitotic initiation. These processes are all crucial for proper cell survival and proliferation and are often deregulated in cancer and other diseases. PMID- 26906461 TI - Long-term Outcomes After Osteochondral Autograft Transfer: A Systematic Review at Mean Follow-up of 10.2 Years. AB - PURPOSE: To evaluate (1) activity level and knee function, (2) reoperation and failure rates, and (3) risk factors for reoperation and failure of osteochondral autograft transfer (OAT) at minimum long-term follow-up. METHODS: A comprehensive review was performed for long-term outcomes after OAT. Studies reported on activity-based outcomes (Tegner Activity Scale) and clinical outcomes (Lysholm score and International Knee Documentation Committee score). Reoperation and failure rates, as defined by the publishing authors, were recorded for each study. Modified Coleman Methodology Scores were calculated to assess study methodological quality. RESULTS: Ten studies with a total of 610 patients with an average age of 27.0 years at the time of surgery and a mean follow-up of 10.2 years were included. The mean defect size was 2.6 cm(2) (range, 0.9 to 20.0 cm(2)). The mean duration of symptoms before surgery was 4.8 years. From preoperative to final follow-up, International Knee Documentation Committee scores and Lysholm scores improved significantly by 42.4 (95% confidence interval [CI], 31.8 to 53.1, P < .001) and 21.1 (95% CI, 12.2 to 30.0, P < .01), respectively. Tegner score did not improve significantly (0.76, 95% CI, -0.83 to 2.36, P = .35). Overall failure rate was 28% and reoperation rate was 19%. Increased age, previous surgery, and defect size positively correlated with increased risk of failure. Concomitant surgical procedures negatively correlated with failure rate. CONCLUSIONS: Overall, OAT showed successful outcomes in 72% of patients at long-term follow-up. Increased age, previous surgery, and defect size correlated positively with failure rate, whereas success improved with concomitant surgical procedures. Nonetheless, this systematic review is limited by heterogeneity in a surgical technique, lesion and patient characteristics, and reporting of nonstandardized outcome measures. LEVEL OF EVIDENCE: Level IV, systematic review of Level I-IV studies. PMID- 26906463 TI - Sustained release of active chemotherapeutics from injectable-solid beta-hairpin peptide hydrogel. AB - MAX8 beta-hairpin peptide hydrogel is a solid, preformed gel that can be syringe injected due to shear-thinning properties and can recover solid gel properties immediately after injection. This behavior makes the hydrogel an excellent candidate as a local drug delivery vehicle. In this study, vincristine, a hydrophobic and commonly used chemotherapeutic, is encapsulated within MAX8 hydrogel and shown to release constantly over the course of one month. Vincristine was observed to be cytotoxic in vitro at picomolar to nanomolar concentrations. The amounts of drug released from the hydrogels over the entire time-course were in this concentration range. After encapsulation, release of vincristine from the hydrogel was observed for four weeks. Further characterization showed the vincristine released during the 28 days remained biologically active, well beyond its half-life in bulk aqueous solution. This study shows that vincristine-loaded MAX8 hydrogels are excellent candidates as drug delivery vehicles, through sustained, low, local and effective release of vincristine to a specific target. Oscillatory rheology was employed to show that the shear-thinning and re-healing, injectable-solid properties that make MAX8 a desirable drug delivery vehicle are unaffected by vincristine encapsulation. Rheology measurements also were used to monitor hydrogel nanostructure before and after drug encapsulation. PMID- 26906465 TI - H1N1 influenza: Is traditional Chinese medicine effective and safe? PMID- 26906464 TI - Probing the Effects and Mechanisms of Electroacupuncture at Ipsilateral or Contralateral ST36-ST37 Acupoints on CFA-induced Inflammatory Pain. AB - Transient receptor potential vanilloid 1 (TRPV1) and associated signaling pathways have been reported to be increased in inflammatory pain signaling. There are accumulating evidences surrounding the therapeutic effect of electroacupuncture (EA). EA can reliably attenuate the increase of TRPV1 in mouse inflammatory pain models with unclear signaling mechanisms. Moreover, the difference in the clinical therapeutic effects between using the contralateral and ipsilateral acupoints has been rarely studied. We found that inflammatory pain, which was induced by injecting the complete Freund's adjuvant (CFA), (2.14 +/- 0.1, p < 0.05, n = 8) can be alleviated after EA treatment at either ipsilateral (3.91 +/- 0.21, p < 0.05, n = 8) or contralateral acupoints (3.79 +/- 0.25, p < 0.05, n = 8). EA may also reduce nociceptive Nav sodium currents in dorsal root ganglion (DRG) neurons. The expression of TRPV1 and associated signaling pathways notably increased after the CFA injection; this expression can be further attenuated significantly in EA treatment. TRPV1 and associated signaling pathways can be prevented in TRPV1 knockout mice, suggesting that TRPV1 knockout mice are resistant to inflammatory pain. Through this study, we have increased the understanding of the mechanism that both ipsilateral and contralateral EA might alter TRPV1 and associated signaling pathways to reduce inflammatory pain. PMID- 26906467 TI - The function of hydrogen sulphide in iron availability: Sulfur nutrient or signaling molecule? AB - Hydrogen sulphide (H2S) has traditionally been considered as a phytotoxin, having deleterious effects on the plant growth and survival. Recently, it was recongnized as a potential signaling molecule involving in physiological regulation similar to nitric oxide (NO) and carbon monoxide (CO) in plants. In a recent study, we mainly focused on the signaling function of H2S in improving adaptation of Zea mays seedlings to iron deficiency. We reported that H2S was closely related to iron uptake, transport, and accumulation, and consequently increased chlorophyll biosynthesis, chloroplast development, and photosynthesis in Z. mays seedlings. Here, we provide more commentary on the signaling roles of H2S in coping with Fe deficiency in plants through increasing sulfur containing metabolites and regulating the expression level of iron homeostasis and sulfur metabolism-related genes in maize seedlings. PMID- 26906466 TI - Thiol-Based Redox Modulation of Soluble Guanylyl Cyclase, the Nitric Oxide Receptor. AB - SIGNIFICANCE: Soluble guanylyl cyclase (sGC), which produces the second messenger cyclic guanosine 3', 5'-monophosphate (cGMP), is at the crossroads of nitric oxide (NO) signaling: sGC catalytic activity is both stimulated by NO binding to the heme and inhibited by NO modification of its cysteine (Cys) thiols (S nitrosation). Modulation of sGC activity by thiol oxidation makes sGC a therapeutic target for pathologies originating from oxidative or nitrosative stress. sGC has an unusually high percentage of Cys for a cytosolic protein, the majority solvent exposed and therefore accessible modulatory targets for biological and pathophysiological signaling. Recent Advances: Thiol oxidation of sGC contributes to the development of cardiovascular diseases by decreasing NO dependent cGMP production and thereby vascular reactivity. This thiol-based resistance to NO (e.g., increase in peripheral resistance) is observed in hypertension and hyperaldosteronism. CRITICAL ISSUES: Some roles of specific Cys thiols have been identified in vitro. So far, it has not been possible to pinpoint the roles of specific Cys of sGC in vivo and to investigate the molecular mechanisms in an animal model. FUTURE DIRECTIONS: The role of Cys as redox sensors, intermediates of activation, and mediators of change in sGC conformation, activity, and dimerization remains largely unexplored. To understand modulation of sGC activity, it is critical to investigate the roles of specific oxidative thiol modifications that are formed during these processes. Where the redox state of sGC thiols contribute to pathologies (vascular resistance and sGC desensitization by NO donors), it becomes crucial to design therapeutic strategies to restore sGC to its normal, physiological thiol redox state. Antioxid. Redox Signal. 26, 137-149. PMID- 26906468 TI - Artificial Intelligence for the Evaluation of Operational Parameters Influencing Nitrification and Nitrifiers in an Activated Sludge Process. AB - Nitrification at a full-scale activated sludge plant treating municipal wastewater was monitored over a period of 237 days. A combination of fluorescent in situ hybridization (FISH) and quantitative real-time polymerase chain reaction (qPCR) were used for identifying and quantifying the dominant nitrifiers in the plant. Adaptive neuro-fuzzy inference system (ANFIS), Pearson's correlation coefficient, and quadratic models were employed in evaluating the plant operational conditions that influence the nitrification performance. The ammonia oxidizing bacteria (AOB) abundance was within the range of 1.55 * 10(8)-1.65 * 10(10) copies L(-1), while Nitrobacter spp. and Nitrospira spp. were 9.32 * 10(9) 1.40 * 10(11) copies L(-1) and 2.39 * 10(9)-3.76 * 10(10) copies L(-1), respectively. Specific nitrification rate (qN) was significantly affected by temperature (r 0.726, p 0.002), hydraulic retention time (HRT) (r -0.651, p 0.009), and ammonia loading rate (ALR) (r 0.571, p 0.026). Additionally, AOB was considerably influenced by HRT (r -0.741, p 0.002) and temperature (r 0.517, p 0.048), while HRT negatively impacted Nitrospira spp. (r -0.627, p 0.012). A quadratic combination of HRT and food-to-microorganism (F/M) ratio also impacted qN (r (2) 0.50), AOB (r (2) 0.61), and Nitrospira spp. (r (2) 0.72), while Nitrobacter spp. was considerably influenced by a polynomial function of F/M ratio and temperature (r (2) 0.49). The study demonstrated that ANFIS could be used as a tool to describe the factors influencing nitrification process at full scale wastewater treatment plants. PMID- 26906469 TI - Improving continuity of care for frequent users of emergency departments: service user and provider perspectives. AB - OBJECTIVE: This study explored service user and provider perspectives on barriers and facilitators of continuity of care for frequent users of emergency departments (ED) participating in a brief intensive case management intervention. METHOD: We conducted semistructured interviews with 20 frequent ED users with mental health and addiction challenges participating in a brief intensive case management intervention, eliciting experiences of care and care continuity. We interviewed 13 service providers working with this population. We used thematic analysis to determine shared and unique barriers and facilitators to continuity of care, and we gave priority to themes reported by both service users and providers. RESULTS: Within fragmented systems of care, strong working relationships between service users and providers, timely access to coordinated services and seamless transitions to needed supports increased perceived care continuity. Barriers to continuity of care included difficulties engaging this population, short intervention duration and the lack of a single accountable service provider to address health and social needs. CONCLUSION: Although brief intensive case management interventions have the potential to improve continuity of care for frequent ED users, continuity of care, especially for people with complex health and social needs, may be compromised by program and personal characteristics as well as lack of broader system integration. PMID- 26906470 TI - Nutritional status in children and adolescents with leukemia: An emphasis on clinical outcomes in low and middle income countries. AB - OBJECTIVE: The purpose of this narrative review is to examine the information available on the nutritional status of children with leukemia in low and middle income countries (LMICs), where the great majority of them live and malnutrition is prevalent, in order to identify best practices and remaining deficits in knowledge. METHODS: Literature relevant to measurement of nutritional status and the impact of nutritional status on important clinical outcomes in this population, and others of relevance, was reviewed. RESULTS: Arm anthropometry provides more accurate information on nutritional status than measures based on body weight in children with cancer. Both over- and under-nutrition are important determinants of tolerance of chemotherapy, compliance with treatment, relapse of disease, and survival. These relationships are subject to change with nutritional intervention. There are valuable roles for educational tools and 'ready-to-use therapeutic-foods'. DISCUSSION: Assessment of nutritional status is mandatory in this population and accomplishable at various levels of sophistication according to available resources. Recognition of the fundamental role of nutritional status in affecting outcomes in children with leukemia is expanding, but knowledge gaps remain. An apparently counter-intuitive strategy of caloric restriction may be worthy of exploration. There is a particular need to establish normative data, including measures of body composition, in children in LMICs. CONCLUSIONS: Developing adaptive clinical practice guidelines for the measurement of nutritional status and for nutritional interventions, incorporating assessment of health-related quality of life, are evident priorities in the care of children with leukemia in LMICs. PMID- 26906472 TI - Design, synthesis, and docking studies of afatinib analogs bearing cinnamamide moiety as potent EGFR inhibitors. AB - Two series of afatinib derivatives bearing cinnamamide moiety (10a-n and 11a-h) were designed, synthesized and evaluated for the IC50 values against four cancer cell lines (A549, PC-3, MCF-7 and Hela). Two selected compounds (10e, 10k) were further evaluated for the inhibitory activity against EGFR and VEGFR2/KDR kinases. Seven of the compounds showed excellent cytotoxicity activity and selectivity with the IC50 values in single-digit MUM to nanomole range. Three of them are equal to more active than positive control afatinib against one or more cell lines. The most promising compound 10k showed the best activity against A549, PC-3, MCF-7 and Hela cancer cell lines and EGFR kinase, with the IC50 values of 0.07 +/- 0.02 MUM, 7.67 +/- 0.97 MUM, 4.65 +/- 0.90 MUM and 4.83 +/- 1.28 MUM, which were equal to more active than afatinib (0.05 +/- 0.01 MUM, 4.1 +/- 2.47 MUM, 5.83 +/- 1.89 MUM and 6.81 +/- 1.77 MUM), respectively. Activity of compounds 10e (IC50 9.1 nM) and 10k (IC50 3.6 nM) against EGFR kinase were equal to the reference compound afatinib (IC50 1.6 nM). Structure-activity relationships (SARs) and docking studies indicated that replacement of the aqueous solubility 4-(dimethylamino)but-2-enamide group by cinnamamide moiety didn't decrease the antitumor activity. The results suggested that methoxy substitution had a significant impact on the activity and methoxy substituted on C-4 or C-2,3,4 position was benefit for the activity. PMID- 26906473 TI - Synthesis and neuroprotective activity of dictyoquinazol A and analogues. AB - A flexible and efficient synthesis of the neuroprotective alkaloid, dictyoquinazol A, is reported. Several structural analogues of the target molecule were produced, and the neuroprotective activity of this series of compounds was investigated using three different cell-based models of stroke. Several of the new compounds were found to have superior activity compared to the natural product. This work has established a new molecular scaffold that holds promise for a novel pharmaceutical treatment for stroke. PMID- 26906475 TI - White light emissive molecular siblings. AB - The design and synthesis of two structurally close and complementarily fluorescent boron based molecular siblings 2 and 3 are reported. The luminescence properties of individual triads are modulated to complement each other by controlling the intramolecular energy transfer in 2 and 3. The binary mixture of 2 and 3 emits white-light. PMID- 26906471 TI - Nanotechnology in diagnosis and treatment of coronary artery disease. AB - Nanotechnology could provide a new complementary approach to treat coronary artery disease (CAD) which is now one of the biggest killers in the Western world. The course of events, which leads to atherosclerosis and CAD, involves many biological factors and cellular disease processes which may be mitigated by therapeutic methods enhanced by nanotechnology. Nanoparticles can provide a variety of delivery systems for cargoes such as drugs and genes that can address many problems within the arteries. In order to improve the performance of current stents, nanotechnology provides different nanomaterial coatings, in addition to controlled-release nanocarriers, to prevent in-stent restenosis. Nanotechnology can increase the efficiency of drugs, improve local and systematic delivery to atherosclerotic plaques and reduce the inflammatory or angiogenic response after intravascular intervention. Nanocarriers have potential for delivery of imaging and diagnostic agents to precisely targeted destinations. This review paper will cover the current applications and future outlook of nanotechnology, as well as the main diagnostic methods, in the treatment of CAD. PMID- 26906474 TI - Synthesis and biological evaluation of new fluorinated and chlorinated indenoisoquinoline topoisomerase I poisons. AB - Fluorine and chlorine are metabolically stable, but generally less active replacements for a nitro group at the 3-position of indenoisoquinoline topoisomerase IB (Top1) poisons. A number of strategies were employed in the present investigation to enhance the Top1 inhibitory potencies and cancer cell growth inhibitory activities of halogenated indenoisoquinolines. In several cases, the new compounds' activities were found to rival or surpass those of similarly substituted 3-nitroindenoisoquinolines, and several unusually potent analogs were discovered through testing in human cancer cell cultures. A hydroxyethylaminopropyl side chain on the lactam nitrogen of two halogenated indenoisoquinoline Top1 inhibitors was found to also impart inhibitory activity against tyrosyl DNA phosphodiesterases 1 and 2 (TDP1 and TDP2), which are enzymes that participate in the repair of DNA damage induced by Top1 poisons. PMID- 26906476 TI - In-situ measurement of the heat transport in defect- engineered free-standing single-layer graphene. AB - Utilizing nanomachining technologies, it is possible to manipulate the heat transport in graphene by introducing different defects. However, due to the difficulty in suspending large-area single-layer graphene (SLG) and limited temperature sensitivity of the present probing methods, the correlation between the defects and thermal conductivity of SLG is still unclear. In this work, we developed a new method for fabricating micro-sized suspended SLG. Subsequently, a focused ion beam (FIB) was used to create nanohole defects in SLG and tune the heat transport. The thermal conductivity of the same SLG before and after FIB radiation was measured using a novel T-type sensor method on site in a dual-beam system. The nanohole defects decreased the thermal conductivity by about 42%. It was found that the smaller width and edge scrolling also had significant restriction on the thermal conductivity of SLG. Based on the calculation results through a lattice dynamics theory, the increase of edge roughness and stronger scattering on long-wavelength acoustic phonons are the main reasons for the reduction in thermal conductivity. This work provides reliable data for understanding the heat transport in a defective SLG membrane, which could help on the future design of graphene-based electrothermal devices. PMID- 26906477 TI - Functional outcomes of infants with Narakas grade 1 birth-related brachial plexus palsy undergoing neurotization compared with infants who did not require surgery. AB - PURPOSE: This study aimed to investigate the functional outcomes of infants who underwent neurotization for shoulder abduction and elbow flexion in Narakas grade 1 birth-related brachial plexus palsy (BRBPP) and compare this cohort to children who progressed past the point of needing intervention. METHODS: A cohort study was conducted at a single center between 1999 and 2010. Two-hundred and eight infants were identified with BRBPP that presented for neurosurgical care as infants. Of those, 38 (18 %) received neurosurgical intervention with approximate 2-year follow-up. Only infants undergoing cranial nerve XI to suprascapular nerve neurotization for shoulder abduction (SA) weakness and medial pectoral nerve to musculocutaneous nerve neurotization for elbow flexion (EF) weakness were included. In addition, 30 infants who improved past the need for surgical intervention and had been followed for close to 24 months were identified for comparison. Descriptive statistics and exploratory analysis were performed using SAS 9.2 and JMP 9.0.2. RESULTS: Shoulder abduction For SA, there were no differences in age at presentation between the operative (6-9 months) and non operative (5-9 months) groups (p = 0.99). Infants in the operative cohort had significantly worse initial function (p = 0.008). At 2-year follow-up, the two groups had become similar (p = 1.0). Elbow flexion For EF, there were no differences in age at presentation between the operative (6-8 months) and non operative (5-8.5 months) groups (p = 0.98). Infants in the operative cohort had significantly worse initial function (p = 0.002). At 2-year follow-up, those two groups had become similar (p = 0.26). CONCLUSIONS: Infants undergoing neurotization for Narakas grade 1 brachial plexus injury had similar long-term function to those who had improved and never required surgery. The preoperative exam findings were significantly different between the intervened and non intervened groups, while the postoperative exam findings were not. PMID- 26906480 TI - Orchid mantis. AB - James O'Hanlon introduces the orchid mantis, a species of preying mantis that resembles flowers. PMID- 26906478 TI - Long-term survival of an infant with diffuse brainstem lesion diagnosed by prenatal MRI: a case report and review of the literature. AB - BACKGROUND: We describe a unique case of expansive diffuse brainstem lesion diagnosed prenatally by magnetic resonance imaging (MRI) with long-term survival. Findings of fetal and postpartum MRI were highly consistent with the characteristics of diffuse brainstem glioma. METHODS: Diagnosis was based on the features of MRI, and histopathology was not confirmed by biopsy. Although the prognosis of diffuse brainstem tumor is usually poor, this child was asymptomatic at birth and the neurological condition is still normal at 4 years of age without any treatment. RESULTS: During routine imaging follow-up, diameters of the expansion have remained stable, while the size of the lesion compared to the posterior fossa size has diminished. In addition to brainstem tumor, a skin lesion of the back was observed and MRI of the thoracic spine showed a large asymptomatic extradural cystic lesion suggesting an arachnoid cyst. The pontine tumor of this infant, in agreement with a few previously reported cases, suggests a subgroup of beneficial outcome of expansive diffuse brainstem lesions, particularly in the neonatal period. DISCUSSION: In this article, we discuss the prognosis and characteristics of pediatric brainstem tumors and differential diagnosis of neonatal brainstem lesions. PMID- 26906479 TI - Ventricular-subcutaneous shunt for the treatment of experimental hydrocephalus in young rats: technical note. AB - BACKGROUND: Hydrocephalus is a complex disease that affects cerebrospinal fluid (CSF) dynamics and is very common in children. To this date, CSF shunting is still the standard treatment for childhood hydrocephalus, but, nevertheless, the effects of such an operation on the developing brain are widely unknown. To help overcome this, experimental models of CSF shunts are surely very useful tools. OBJECTIVE: The objective of this study was to describe a feasible and reliable technique of an adapted ventricular-subcutaneous shunt for the treatment of kaolin-induced hydrocephalus in young rats. METHODS: We developed a ventricular subcutaneous shunt (VSCS) technique which was used in 31 Wistar young rats with kaolin-induced hydrocephalus. Hydrocephalus was induced at 7 days of age, and shunt implantation was performed 7 days later. Our technique used a 0.7-mm gauge polypropylene catheter tunneled to a subcutaneous pocket created over the animal's back and inserted into the right lateral ventricle. All animals were sacrificed 14 days after shunt insertion. RESULTS: Twenty-four rats survived and remained well until the study was ended. No major complications were seen. Their weight gain went back to normal. They all underwent ambulatory behavioral testing prior and after VSCS, which showed improvement in their motor skills. We have also obtained magnetic resonance (MR) scans of 16 pups confirming reduction of ventricular size after shunting and indicating effective treatment. Histopathological analysis of brain samples before and after shunting showed reversion of ependymal and corpus callosum disruption, as well as fewer reactive astrocytes in shunted animals. CONCLUSIONS: An experimental CSF shunt technique was devised. Excessive CSF of hydrocephalic rats is diverted into the subcutaneous space where it can be resorbed. This technique has a low complication rate and is effective. It might be applied to various types of experimental studies involving induction and treatment of hydrocephalus. PMID- 26906481 TI - Tunicates. AB - Tunicates, also called urochordates, are an extremely diverse subphylum of the Chordata, a phylum that also contains the vertebrates and cephalochordates. The tunicates seem to have undergone especially rapid evolution: while remaining exclusively marine, they have radiated to occupy habitats ranging from shallow water, to near shore to the open ocean and the deep sea. Furthermore, they have evolved a variety of remarkable reproductive strategies, combining asexual and sexual modes of reproduction that allow for very rapid expansion of populations. An outstanding question is what happened to allow tunicates to evolve so much faster than their nearest relatives, cephalochordates and vertebrates. PMID- 26906482 TI - Light-controlled intracellular transport in Caenorhabditis elegans. AB - To establish and maintain their complex morphology and function, neurons and other polarized cells exploit cytoskeletal motor proteins to distribute cargoes to specific compartments. Recent studies in cultured cells have used inducible motor protein recruitment to explore how different motors contribute to polarized transport and to control the subcellular positioning of organelles. Such approaches also seem promising avenues for studying motor activity and organelle positioning within more complex cellular assemblies, but their applicability to multicellular in vivo systems has so far remained unexplored. Here, we report the development of an optogenetic organelle transport strategy in the in vivo model system Caenorhabditis elegans. We demonstrate that movement and pausing of various organelles can be achieved by recruiting the proper cytoskeletal motor protein with light. In neurons, we find that kinesin and dynein exclusively target the axon and dendrite, respectively, revealing the basic principles for polarized transport. In vivo control of motor attachment and organelle distributions will be widely useful in exploring the mechanisms that govern the dynamic morphogenesis of cells and tissues, within the context of a developing animal. PMID- 26906483 TI - The phylogenetic affinities of the extinct glyptodonts. AB - Among the fossils of hitherto unknown mammals that Darwin collected in South America between 1832 and 1833 during the Beagle expedition were examples of the large, heavily armored herbivores later known as glyptodonts. Ever since, glyptodonts have fascinated evolutionary biologists because of their remarkable skeletal adaptations and seemingly isolated phylogenetic position even within their natural group, the cingulate xenarthrans (armadillos and their allies). In possessing a carapace comprised of fused osteoderms, the glyptodonts were clearly related to other cingulates, but their precise phylogenetic position as suggested by morphology remains unresolved. To provide a molecular perspective on this issue, we designed sequence-capture baits using in silico reconstructed ancestral sequences and successfully assembled the complete mitochondrial genome of Doedicurus sp., one of the largest glyptodonts. Our phylogenetic reconstructions establish that glyptodonts are in fact deeply nested within the armadillo crown group, representing a distinct subfamily (Glyptodontinae) within family Chlamyphoridae. Molecular dating suggests that glyptodonts diverged no earlier than around 35 million years ago, in good agreement with their fossil record. Our results highlight the derived nature of the glyptodont morphotype, one aspect of which is a spectacular increase in body size until their extinction at the end of the last ice age. PMID- 26906484 TI - Plant Organogenesis: Rules of Order. AB - Plant lateral roots have a defined developmental pattern and shape, but a key question is whether strict regulation underlies observed regularity. A new study uses long-term in toto live imaging and simulations to show that organogenesis rather follows self-organizing principles. PMID- 26906485 TI - Palaeontology: The Point of No Return in the Fossil Record of Eusociality. AB - The evolution of eusociality is one of the major transitions in the history of life, particularly in the insects. Now, fossil termites and ants from Burmese amber offer insights into early stages of eusociality in the Lower Cretaceous. PMID- 26906486 TI - Eco-evolutionary Biology: Feeding and Feedback Loops. AB - A dogma in ecology and evolution holds that the environment is an extrinsic force that is not, in turn, shaped by the adaptive evolution of species. Recent work on stickleback life history, community ecology and speciation challenges this dogma. PMID- 26906487 TI - Cancer: The Transforming Power of Cell Competition. AB - The tumour-host microenvironment plays key roles in cancer, but the mechanisms involved are not fully understood. Two new studies provide insight into this problem by showing that through cell competition, a fitness-sensing process that usually eliminates defective cells, pre-cancerous lesions signal the death of surrounding tissue that in turn promotes their neoplastic transformation. PMID- 26906488 TI - Insect Navigation: How Do Wasps Get Home? AB - Bees and wasps are famous for many things, including elaborate flights to learn where their nest is. A new study provides precise, three-dimensional details of a wasp's head and body movements during such flights and reconstructs what the wasp sees. PMID- 26906489 TI - Adaptive Evolution: Don't Fix What's Broken. AB - Evolution of budding yeast after the removal of an important component of the polarization machinery, BEM1, followed reproducible evolutionary trajectories governed by epistasis. Interestingly, cells restored polarization not by finding a substitute for Bem1 but by rendering its function dispensable. PMID- 26906490 TI - Sex Determination: Separate Sexes Are a Double Turnoff in Melons. AB - Flowers with only one sexual function typically result from the developmental suppression of the other. A recent study that shows how this is achieved has important implications for models of the evolution of separate sexes in plants. PMID- 26906491 TI - Evolution: Causality and the Origin of Parasitism. AB - The first comparison of parasitic trypanosomatids to their free-living relatives reveals that some characteristics once linked to parasitism actually predate it. Parallel comparisons of other parasites suggest we need to rethink the drivers and consequences of the parasitic lifestyle. PMID- 26906492 TI - Gene Amplification: Trophoblast Giant Cells Use All the Tricks. AB - Evolutionary gene duplication, developmental endoreduplication and selective gene amplification are alternative strategies for increasing gene copy number. When these processes occur together, things get really interesting, and new work shows that is the lifestyle of cells in the placenta. PMID- 26906493 TI - Atropisomerism about Aryl-C(sp(3)) Bonds: Conformational Behavior of Substituted Phenylcyclohexanes in Solution. AB - A catalytic hydrogenation of cannabidiol derivatives known as phenylcyclohexenes was used to prepare epimeric (1R,1S) and/or rotameric (M,P) phenylcyclohexanes. The reaction is diastereoselective, in favor of the 1S epimer, when large groups are attached to the phenyl ring. For each epimer, variable-temperature NMR experiments, including EXSY spectroscopy and DFT calculations, were used to determine the activation energies of the conformational exchange arising from the restricted rotation about the aryl-C(sp(3)) bond that led to two unequally populated rotamers. The conformational preference arises essentially from steric interactions between substituents vicinal to the pivot bond. The conformers of epimers (1S)-2e,f show high rotational barriers of up to 92 kJ mol(-1), unlike those of (1R)-2e,f and with much lower barriers of ~72 kJ mol(-1). The height of the barriers not only depends on the substituents at the axis of chirality but also is influenced by the position of a methyl group on the monoterpene ring. The feature most favorable to high rotational barriers is when the methyl at C1 lies equatorially. This additional substituent effect, highlighted for the first time, seems fundamental to allowing atropisomerism in hindered ortho-substituted phenylcyclohexanes. PMID- 26906494 TI - Anxiety in adolescent epilepsy. A clinimetric analysis. AB - Background Anxiety and depression have been considered to be neglected disorders in epilepsy. Because panic disorder is one of the most important anxiety disorders, it has been problematic to use very comprehensive anxiety questionnaires in epilepsy patients, as panic attacks and epileptic seizures, although two distinct clinical entities from a diagnostic point of view, show a significant overlap of symptoms. Aims We have focused on single items for anxiety and depression as screening candidates in adolescent epilepsy. Methods The individual panic attack item in the Screen for Children Anxiety Related Emotional Disorders Scale (SCARED) and the single depression item in the Kellner Symptom Questionnaire were tested. Our samples consisted of adolescent patients with epilepsy and a matched control group with healthy participants, as well as two numerical groups acting as controls. Results The single panic attack item identified panic anxiety in 24.1% in the group of patients with epilepsy and 0.0% in the matched control group (p = 0.01). The single depression item identified 52.2% with depression in the epilepsy group and 6.2% in the matched control group (p = 0.001). Conclusion As screening instruments, single items of panic attack and depression are sufficient to screen for these affective states in adolescent epilepsy. The clinical implications are that it is important to be quite specific when screening for depression and panic attacks in adolescent patients with epilepsy. PMID- 26906495 TI - OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY TO ASSESS PIGMENT EPITHELIAL DETACHMENT. PMID- 26906496 TI - A convenient approach to an advanced intermediate toward the naturally occurring, bioactive 6-substituted 5-hydroxy-4-aryl-1H-quinolin-2-ones. AB - 5-Hydroxy-4-aryl-3,4-dihydro-1H-quinolin-2-ones are a small family of natural products isolated from fungal strains of Penicillium and Aspergillus. Most of its members, which are insecticides and anthelmintics, carry an isoprenoid C-6 side chain. The synthesis of a 6-propenyl-substituted advanced intermediate for the total synthesis of these natural products is presented in this paper. This was achieved through the stereoselective construction of a beta,beta-diarylacrylate derivative from 6-nitrosalicylaldehyde, using a Wittig olefination and a Heck Matsuda arylation, followed by a selective Fe(0)-mediated reductive cyclization. Installation of the 6-propenyl side chain was performed by 5-O-allylation of the heterocycle, followed by Claisen rearrangement and conjugative migration of the allyl double bond, as the key steps. The Grubbs II-catalyzed olefin cross metathesis of the 6-allyl moiety with 2-methylbut-2-ene to afford a precursor of peniprequinolone is also reported. PMID- 26906497 TI - Simulation of oil pollution in the Persian Gulf near Assaluyeh oil terminal. AB - Numerical simulation of oil slick movement with respect to tidal factors and wind effects was performed in order to counteract oil pollution in the Persian Gulf. First, a flow model was invoked with respect to water level fluctuations. The main tidal constituents were applied to the model using the initial conditions of water level variations in the Hormuz Strait near the Hangam Island. The movement of oil pollution was determined due to wind, tide and temperature effects and confirmed by applying a verified field results. Simulations were focused near an important terminal in the Persian Gulf, Assaluyeh Port. The results were led to preparing a risk-taking map in a parallel research for the Persian Gulf. PMID- 26906498 TI - Levels of endothelial cell-specific molecule-1 (ESM-1) in overt hypothyroidisim. AB - PURPOSE: Endothelial cell-specific molecule-1, endocan, is a proteoglycan that is expressed by the vascular endothelium. Endocan can be a biomarker of endothelial dysfunction caused by endothelial cell-dependent disorders. Endothelial dysfunction is an early step of atherosclerosis and is developed in hypothyroid patients, which indicates an association between hypothyroidism and atherosclerosis. Therefore, we aimed to investigate whether circulating endocan levels are associated with endothelial dysfunction in overt hypothyroid patients. MATERIALS AND METHODS: Forty patients with hypothyroidism diagnosed in the last 5 years and 30 healthy subjects were recruited. RESULTS: The mean endocan value in all patients was 0.63 +/- 0.26 pg/ml, which was higher than that in controls (0.36 +/- 0.10 pg/ml, p < 0.05). When we subgrouped the patients as hypothyroid and euthyroid, all groups demonstrated significantly different endocan levels, and hypothyroid patients had the highest endocan levels. A correlation analysis demonstrated that endocan levels were positively correlated with body mass index (BMI), thyroid-stimulating hormone (TSH), anti-thyroid peroxidase, and anti thyroglobulin and negatively correlated with free thyroid hormone 4 (FT4) and vitamin D levels. In addition, in the patient group, endocan levels were correlated with FT4 levels independently in a covariance analysis. CONCLUSIONS: The circulating endocan level increased in hypothyroid patients, suggesting that endocan levels may be an early biomarker of the development of endothelial dysfunction in patients with hypothyroidism. They may also prove useful in the prediction of cardiovascular diseases after further studies using cardiovascular disease biomarkers. In addition, targeting endocan levels to decrease cardiovascular risk may be a new treatment strategy in these patients. PMID- 26906499 TI - Focus on neural computation and theory. PMID- 26906500 TI - Conceptual and technical advances define a key moment for theoretical neuroscience. PMID- 26906501 TI - Building functional networks of spiking model neurons. AB - Most of the networks used by computer scientists and many of those studied by modelers in neuroscience represent unit activities as continuous variables. Neurons, however, communicate primarily through discontinuous spiking. We review methods for transferring our ability to construct interesting networks that perform relevant tasks from the artificial continuous domain to more realistic spiking network models. These methods raise a number of issues that warrant further theoretical and experimental study. PMID- 26906502 TI - Using goal-driven deep learning models to understand sensory cortex. AB - Fueled by innovation in the computer vision and artificial intelligence communities, recent developments in computational neuroscience have used goal driven hierarchical convolutional neural networks (HCNNs) to make strides in modeling neural single-unit and population responses in higher visual cortical areas. In this Perspective, we review the recent progress in a broader modeling context and describe some of the key technical innovations that have supported it. We then outline how the goal-driven HCNN approach can be used to delve even more deeply into understanding the development and organization of sensory cortical processing. PMID- 26906503 TI - Confidence and certainty: distinct probabilistic quantities for different goals. AB - When facing uncertainty, adaptive behavioral strategies demand that the brain performs probabilistic computations. In this probabilistic framework, the notion of certainty and confidence would appear to be closely related, so much so that it is tempting to conclude that these two concepts are one and the same. We argue that there are computational reasons to distinguish between these two concepts. Specifically, we propose that confidence should be defined as the probability that a decision or a proposition, overt or covert, is correct given the evidence, a critical quantity in complex sequential decisions. We suggest that the term certainty should be reserved to refer to the encoding of all other probability distributions over sensory and cognitive variables. We also discuss strategies for studying the neural codes for confidence and certainty and argue that clear definitions of neural codes are essential to understanding the relative contributions of various cortical areas to decision making. PMID- 26906504 TI - Efficient codes and balanced networks. AB - Recent years have seen a growing interest in inhibitory interneurons and their circuits. A striking property of cortical inhibition is how tightly it balances excitation. Inhibitory currents not only match excitatory currents on average, but track them on a millisecond time scale, whether they are caused by external stimuli or spontaneous fluctuations. We review, together with experimental evidence, recent theoretical approaches that investigate the advantages of such tight balance for coding and computation. These studies suggest a possible revision of the dominant view that neurons represent information with firing rates corrupted by Poisson noise. Instead, tight excitatory/inhibitory balance may be a signature of a highly cooperative code, orders of magnitude more precise than a Poisson rate code. Moreover, tight balance may provide a template that allows cortical neurons to construct high-dimensional population codes and learn complex functions of their inputs. PMID- 26906505 TI - The mechanics of state-dependent neural correlations. AB - Simultaneous recordings from large neural populations are becoming increasingly common. An important feature of population activity is the trial-to-trial correlated fluctuation of spike train outputs from recorded neuron pairs. Similar to the firing rate of single neurons, correlated activity can be modulated by a number of factors, from changes in arousal and attentional state to learning and task engagement. However, the physiological mechanisms that underlie these changes are not fully understood. We review recent theoretical results that identify three separate mechanisms that modulate spike train correlations: changes in input correlations, internal fluctuations and the transfer function of single neurons. We first examine these mechanisms in feedforward pathways and then show how the same approach can explain the modulation of correlations in recurrent networks. Such mechanistic constraints on the modulation of population activity will be important in statistical analyses of high-dimensional neural data. PMID- 26906508 TI - Targeting PTEN interactions for Alzheimer's disease. PMID- 26906506 TI - Computational principles of memory. AB - The ability to store and later use information is essential for a variety of adaptive behaviors, including integration, learning, generalization, prediction and inference. In this Review, we survey theoretical principles that can allow the brain to construct persistent states for memory. We identify requirements that a memory system must satisfy and analyze existing models and hypothesized biological substrates in light of these requirements. We also highlight open questions, theoretical puzzles and problems shared with computer science and information theory. PMID- 26906509 TI - Gaining on reward prediction errors. PMID- 26906510 TI - Schizophrenia and brain volume genetic covariation. PMID- 26906507 TI - Computational psychiatry as a bridge from neuroscience to clinical applications. AB - Translating advances in neuroscience into benefits for patients with mental illness presents enormous challenges because it involves both the most complex organ, the brain, and its interaction with a similarly complex environment. Dealing with such complexities demands powerful techniques. Computational psychiatry combines multiple levels and types of computation with multiple types of data in an effort to improve understanding, prediction and treatment of mental illness. Computational psychiatry, broadly defined, encompasses two complementary approaches: data driven and theory driven. Data-driven approaches apply machine learning methods to high-dimensional data to improve classification of disease, predict treatment outcomes or improve treatment selection. These approaches are generally agnostic as to the underlying mechanisms. Theory-driven approaches, in contrast, use models that instantiate prior knowledge of, or explicit hypotheses about, such mechanisms, possibly at multiple levels of analysis and abstraction. We review recent advances in both approaches, with an emphasis on clinical applications, and highlight the utility of combining them. PMID- 26906512 TI - CNOs Gearing Up While Many are Winding Down: The Late Career DNP. AB - Nurses are knowledge workers. The evidence that informs our practice is ever changing, and we recognize that one of the obligations of knowledge work is lifelong learning. There is a newly emerging phenomenon occurring in our profession--one that we did not see a decade ago. Increasingly, chief nursing officers (CNOs) are pursuing advanced degrees late in their careers. This month, we will shine the spotlight on what's driving this change and gain insights from conversations with 3 CNOs, all recently having attained a DNP, after an astounding, collective 110-plus years in practice. PMID- 26906511 TI - Folic Acid Attenuates Vascular Endothelial Cell Injury Caused by Hypoxia via the Inhibition of ERK1/2/NOX4/ROS Pathway. AB - Coronary artery disease is a disease with high morbidity and mortality, in which vascular endothelial dysfunction plays an important role. Hypoxia leads to the inflammation and oxidative stress in endothelial cells, which results in the endothelial injury. The present study was designed to investigate the protective effect and mechanism of folic acid on hypoxia-induced injury in human umbilical vein endothelial cells (HUVEC). Cell counting Kit was used to detect cell survival rate, and apoptotic cells were detected by Hoechst 33258 staining. Intracellular reactive oxygen species (ROS) level was measured using dichloro dihydro-fluorescein diacetate staining. Western blot was used to determine the protein expressions of extracellular signal protein kinase 1/2 (ERK1/2) and phosphorylated ERK1/2 (p-ERK1/2), NOX4 subunit of NAPDH and endothelial nitric oxide synthase (eNOS). Folic acid significantly increased the cell survival rate and decreased the apoptosis of HUVECs treated with folic acid compared with hypoxia-treated HUVEC. Folic acid also decreased ROS level, while it increased the nitrite content in HUVECs. In addition, folic acid decreased protein expressions of NOX4 and p-ERK1/2, while it increased the protein expression of eNOS in HUVECs. Furthermore, N-acetyl cysteine (NAC), the antioxidant, had similar effect on the cell survival rate and the apoptosis. In addition, DPI (NOX4 inhibitor) and U0126 (ERK1/2 inhibitor) rather than NAC decreased the protein expression of NOX4. NAC, DPI, and U0126 increased the protein expression of eNOS. Furthermore, U0126 rather than DPI and NAC decreased the protein expression of p-ERK1/2. Taken together, the results suggested that hypoxia decreased the cell survival rate and induced apoptosis via ERK1/2/NOX4/ROS pathway, which could be the target of folic acid in protecting the HUVECs from injury caused by hypoxia. PMID- 26906513 TI - Celebrate Certified Nurses. AB - Annually, Certified Nurses Day honors nurses worldwide who contribute to better patient outcomes through board certification in their specialty. Certification affirms advanced knowledge, skill, and practice to meet the challenges of modern nursing and our shared goal of a healthy citizenry. In this month's Magnet(r) Perspectives column, the value of certification is discussed and why this credential promotes environments of nursing excellence. PMID- 26906514 TI - Big Data, Big Challenges: Implications for Chief Nurse Executives. AB - As systems evolve over time, their natural tendency is to become increasingly more complex. Studies in the field of complex systems have generated new perspectives on the application of management strategies in health systems. Much of this research appears as a natural extension of the cross-disciplinary field of systems theory. In this edition, I begin a series of articles on the growing challenge faced by nurse administrators of finding value in the vast amounts of information collected by health systems today. PMID- 26906515 TI - Structure and Suggestions for System Magnet(r) Designation: Part 1. AB - Achieving Magnet designation as a system requires careful planning and strategy on the part of nursing leaders. This article delineates system structures to support success. PMID- 26906516 TI - Innovating Traditional Nursing Administration Challenges. AB - The evolving and complex practice environment calls for new mindsets among nurse leaders, academics, and nurse innovators to envision innovative ways to manage and optimize traditional tasks and processes in nursing administration. The purpose of this article is to present 3 case studies that used linear programming and simulation to innovate staffing enterprises, financial management of healthcare systems, and curricula development. PMID- 26906517 TI - Increasing RN Accountability in Professional Practice: Development of a Pain Reassessment Documentation Scorecard. AB - Leaders are challenged to find effective ways to increase ownership and accountability in the nurses' practice. Two hospitals, a 462-acute care bed facility (hospital A) and a 324-bed children's and women's hospital (hospital B), located on 1 campus in Southern California were the setting for a unique project targeted at monitoring adherence with pain management guidelines. The use of an auditing process through a computer-generated report and the development of an individual report card for each nurse provided specific performance data related to accountability and compliance in regard to documenting pain reassessment in the electronic medical record. PMID- 26906518 TI - RN Perceptions of a Newly Adopted Electronic Health Record. AB - OBJECTIVE: The purpose of this study was to understand nurses' perceptions of a newly adopted electronic health record (EHR). BACKGROUND: As use of EHRs in hospital settings increases, leaders prepare staff members for change. There is limited information about impacts of EHR adoption on RNs using EHRs at the point of care. METHODS: Clinical RNs were surveyed about 3 domains (ease of use, usefulness, and attitude) before and after implementation of an EHR. A small subset of nurses was interviewed for a deeper understanding of perceptions associated with this change. RESULTS: One year after adoption, nurses believed that the EHR did not improve patient care, the learning curve was steep, and they had lower confidence using the EHR than anticipated. Nurses commented on both their frustration and optimism about EHRs. CONCLUSIONS: This study provides insight into RNs' perceptions of an EHR, providing important information for nursing administrators. PMID- 26906519 TI - Cultural Awareness Among Nursing Staff at an Academic Medical Center. AB - OBJECTIVE: The goal is to identify areas for targeted improvement in regard to cultural awareness and competence among nursing staff and in the work environment. BACKGROUND: Many facilities have initiated programs to facilitate cultural competence development among nursing staff; however, there has been little examination of the effect of these initiatives, assessment of experienced nurses' cultural awareness, or investigation of nurse leader's role in promoting cultural competence in the literature. METHODS: In this cross-sectional descriptive study, a cultural awareness survey was modified and electronically distributed to all registered nurses and assistive personnel at an academic medical center. RESULTS: The modified survey instrument showed good reliability and validity among the study population. Most nursing staff exhibited a moderate to high level of cultural awareness and held positive opinions about nursing leadership and the work environment with regard to cultural issues. CONCLUSIONS: In increasingly diverse work environments, assessing the cultural awareness of nursing staff enables nurse leaders to evaluate efforts in promoting cultural competence and to identify specific areas in which to target staff development efforts and leadership training. PMID- 26906520 TI - Comparison of new and conventional versions of model-based iterative reconstruction in reduced-dose computed tomography for diagnosis of hepatic steatosis. AB - PURPOSE: To compare new and conventional versions of model-based iterative reconstruction (MBIR) in reduced-dose computed tomography (CT) in terms of diagnostic performance for hepatic steatosis. MATERIALS AND METHODS: Images were reconstructed from standard-dose and aggressively reduced-dose (the dose-length product was reduced by 91 %) unenhanced abdominopelvic CT scans of 86 patients using filtered back projection (SD-FBP) and new and conventional versions of MBIR (RD-MBIRn and RD-MBIRc), respectively. The mean CT attenuation of the liver (CT[L]) and the spleen as well as the ratio of these parameters (CT[L/S]) were calculated. CT[L] <48 Hounsfield units (HU) and CT[L/S] <1.1 were applied to SD FBP (used as the reference standard; the number of positive patients was 12 and 14, respectively), RD-MBIRn, and RD-MBIRc. RESULTS: CT[L]s in SD-FBP/RD-MBIRn/RD MBIRc were 56.9/55.9/52.8 HU. The difference in CT[L] between RD-MBIRn and SD-FBP was within +/-5.0 HU in most cases. The sensitivity/specificity/accuracy of CT[L] <48 HU in RD-MBIRn and RD-MBIRc were 1.00/0.97/0.98 and 1.00/0.92/0.93, respectively, showing that RD-MBIRn permits significant improvements in specificity and accuracy (P < 0.05, McNemar test). For CT[L/S] <1.1, these values were 0.79/0.97/0.94 and 0.79/0.97/0.94 in RD-MBIRn and RD-MBIRc, respectively. CONCLUSION: When CT[L] <48 HU was applied, RD-MBIRn presented a significantly improved hepatic steatosis diagnostic performance compared with RD-MBIRc; indeed, it was almost equivalent to that afforded by SD-FBP. PMID- 26906521 TI - Effects of Chemically Modified Messenger RNA on Protein Expression. AB - Chemically modified nucleotides play significant roles in the effectiveness of mRNA translation. Here, we describe the synthesis of two sets of chemically modified mRNAs [encoding firefly Luciferase (FLuc) and enhanced green fluorescent protein (eGFP), respectively], evaluation of protein expression, and correlation analysis of expression level under various conditions. The results indicate that chemical modifications of mRNAs are able to significantly improve protein expression, which is dependent on cell types and coding sequences. Moreover, eGFP mRNAs with N1-methylpseudouridine (me(1)psi), 5-methoxyuridine (5moU), and pseudouridine (psi) modifications ranked top three in cell lines tested. Interestingly, 5moU-modified eGFP mRNA was more stable than other eGFP mRNAs. Consequently, me(1)psi, 5moU, and psi are promising nucleotides for chemical modification of mRNAs. PMID- 26906522 TI - Inhibitor design against JNK1 through e-pharmacophore modeling docking and molecular dynamics simulations. AB - c-Jun-NH2 terminal kinases (JNKs) come under a class of serine/threonine protein kinases and are encoded by three genes, namely JNK1, JNK2 and JNK3. Human JNK1 is a cytosolic kinase belonging to mitogen-activated protein kinase (MAPK) family, which plays a major role in intracrinal signal transduction cascade mechanism. Overexpressed human JNK1, a key kinase interacts with other kinases involved in the etiology of many cancers, such as skin cancer, liver cancer, breast cancer, brain tumors, leukemia, multiple myeloma and lymphoma. Thus, to unveil a novel human JNK1 antagonist, receptor-based pharmacophore modeling was performed with the available eighteen cocrystal structures of JNK1 in the protein data bank. Eighteen e-pharmacophores were generated from the 18 cocrystal structures. Four common e-pharmacophores were developed from the 18 e-pharmacophores, which were used as three-dimensional (3D) query for shape-based similarity screening against more than one million small molecules to generate a JNK1 ligand library. Rigid receptor docking (RRD) performed using GLIDE v6.3 for the 1683 compounds from in house library and 18 cocrystal ligands with human JNK1 from lower stringency to higher stringency revealed 17 leads. Further to derive the best leads, dock complexes obtained from RRD were studied further with quantum-polarized ligand docking (QPLD), induced fit docking (IFD) and molecular mechanics/generalized Born surface area (MM-GBSA). Four leads have showed lesser binding free energy and better binding affinity towards JNK1 compared to 18 cocrystal ligands. Additionally, JNK1-lead1 complex interaction stability was reasserted using 50 ns MD simulations run and also compared with the best resolute cocrystal structure using Desmond v3.8. Thus, the results obtained from RRD, QPLD, IFD and MD simulations indicated that lead1 might be used as a potent antagonist toward human JNK1 in cancer therapeutics. PMID- 26906523 TI - A FIB-nanotomography method for accurate 3D reconstruction of open nanoporous structures. AB - We present an automated focused ion beam nanotomography method for nanoporous microstructures with open porosity, and apply it to reconstruct nanoporous gold (np-Au) structures with ligament sizes on the order of a few tens of nanometers. This method uses serial sectioning of a well-defined wedge-shaped geometry to determine the thickness of individual slices from the changes in the sample width in successive cross-sectional images. The pore space of a selected region of the np-Au is infiltrated with ion-beam-deposited Pt composite before serial sectioning. The cross-sectional images are binarized and stacked according to the individual slice thicknesses, and then processed using standard reconstruction methods. For the image conditions and sample geometry used here, we are able to determine the thickness of individual slices with an accuracy much smaller than a pixel. The accuracy of the new method based on actual slice thickness is assessed by comparing it with (i) a reconstruction using the same cross-sectional images but assuming a constant slice thickness, and (ii) a reconstruction using traditional FIB-tomography method employing constant slice thickness. The morphology and topology of the structures are characterized using ligament and pore size distributions, interface shape distribution functions, interface normal distributions, and genus. The results suggest that the morphology and topology of the final reconstructions are significantly influenced when a constant slice thickness is assumed. The study reveals grain-to-grain variations in the morphology and topology of np-Au. PMID- 26906524 TI - Spatial Access to Primary Care Providers in Appalachia: Evaluating Current Methodology. AB - PURPOSE: The goal of this research was to examine spatial access to primary care physicians in Appalachia using both traditional access measures and the 2-step floating catchment area (2SFCA) method. Spatial access to care was compared between urban and rural regions of Appalachia. METHODS: The study region included Appalachia counties of Pennsylvania, Ohio, Kentucky, and North Carolina. Primary care physicians during 2008 and total census block group populations were geocoded into GIS software. Ratios of county physicians to population, driving time to nearest primary care physician, and various 2SFCA approaches were compared. RESULTS: Urban areas of the study region had shorter travel times to their closest primary care physician. Provider to population ratios produced results that varied widely from one county to another because of strict geographic boundaries. The 2SFCA method produced varied results depending on the distance decay weight and variable catchment size techniques chose. 2SFCA scores showed greater access to care in urban areas of Pennsylvania, Ohio, and North Carolina. CONCLUSION: The different parameters of the 2SFCA method-distance decay weights and variable catchment sizes-have a large impact on the resulting spatial access to primary care scores. The findings of this study suggest that using a relative 2SFCA approach, the spatial access ratio method, when detailed patient travel data are unavailable. The 2SFCA method shows promise for measuring access to care in Appalachia, but more research on patient travel preferences is needed to inform implementation. PMID- 26906525 TI - Breast Density Knowledge and Awareness: A Review of Literature. AB - OBJECTIVES: We reviewed the literature on breast density knowledge and breast density awareness to explore what challenges are faced by this area of research. METHOD: A review of PubMED, PsycINFO, and CINAHL databases was performed. Studies were published in peer-reviewed journals (in all years available) and written in English. The broad search terms used were ["breast density"] AND ["knowledge" OR "awareness"]. Eligible articles were included in the final analysis after meeting the following inclusion criteria: (1) the records had to quantitatively examine and report breast density knowledge and awareness, (2) the number of participants in the sample had to be clearly specified, and (3) studies reporting differences in breast density knowledge and awareness between racial and ethnic groups were included in the review. RESULTS: Of the 277 articles identified, only 5 met inclusion criteria and addressed breast density knowledge and awareness. Characteristics of studies and results were examined. CONCLUSIONS: There is insufficient evidence to determine a pattern of breast density knowledge and awareness in women. More quality studies are needed that focus on how well women understand the relationship between breast density, breast cancer risk, and breast cancer screening, especially in diverse populations. PMID- 26906527 TI - Targeting cancer cachexia: we're on the way. PMID- 26906526 TI - Anamorelin in patients with non-small-cell lung cancer and cachexia (ROMANA 1 and ROMANA 2): results from two randomised, double-blind, phase 3 trials. AB - BACKGROUND: Patients with advanced cancer frequently experience anorexia and cachexia, which are associated with reduced food intake, altered body composition, and decreased functionality. We assessed anamorelin, a novel ghrelin receptor agonist, on cachexia in patients with advanced non-small-cell lung cancer and cachexia. METHODS: ROMANA 1 and ROMANA 2 were randomised, double blind, placebo-controlled phase 3 trials done at 93 sites in 19 countries. Patients with inoperable stage III or IV non-small-cell lung cancer and cachexia (defined as >=5% weight loss within 6 months or body-mass index <20 kg/m(2)) were randomly assigned 2:1 to anamorelin 100 mg orally once daily or placebo, with a computer-generated randomisation algorithm stratified by geographical region, cancer treatment status, and weight loss over the previous 6 months. Co-primary efficacy endpoints were the median change in lean body mass and handgrip strength over 12 weeks and were measured in all study participants (intention-to-treat population). Both trials are now completed and are registered with ClinicalTrials.gov, numbers NCT01387269 and NCT01387282. FINDINGS: From July 8, 2011, to Jan 28, 2014, 484 patients were enrolled in ROMANA 1 (323 to anamorelin, 161 to placebo), and from July 14, 2011, to Oct 31, 2013, 495 patients were enrolled in ROMANA 2 (330 to anamorelin, 165 to placebo). Over 12 weeks, lean body mass increased in patients assigned to anamorelin compared with those assigned to placebo in ROMANA 1 (median increase 0.99 kg [95% CI 0.61 to 1.36] vs -0.47 kg [-1.00 to 0.21], p<0.0001) and ROMANA 2 (0.65 kg [0.38 to 0.91] vs -0.98 kg [-1.49 to -0.41], p<0.0001). We noted no difference in handgrip strength in ROMANA 1 (-1.10 kg [-1.69 to -0.40] vs -1.58 kg [-2.99 to -1.14], p=0.15) or ROMANA 2 (-1.49 kg [-2.06 to -0.58] vs -0.95 kg [-1.56 to 0.04], p=0.65). There were no differences in grade 3-4 treatment-related adverse events between study groups; the most common grade 3-4 adverse event was hyperglycaemia, occurring in one (<1%) of 320 patients given anamorelin in ROMANA 1 and in four (1%) of 330 patients given anamorelin in ROMANA 2. INTERPRETATION: Anamorelin significantly increased lean body mass, but not handgrip, strength in patients with advanced non-small-cell lung cancer. Considering the unmet medical need for safe and effective treatments for cachexia, anamorelin might be a treatment option for patients with cancer anorexia and cachexia. FUNDING: Helsinn Therapeutics. PMID- 26906528 TI - [Not Available]. PMID- 26906529 TI - [Not Available]. PMID- 26906530 TI - [Exists an Obligation to be Healthy? Ethical Limits of Medical Prevention]. AB - An obligation to be healthy in the sauce of a categorical imperative "You shall change your life!" (P. Sloterdijk) does not exist. There is however a moral responsibility to shape ones own life in such a way that the resulting potentials for development can be realized within one owns possibilities (I. Kant). The example of predictive medicine illustrates, why the right not to know can be a responsible way of self governance when dealing with the knowledge of modern biomedicine. This allows the setting of limits within prevention, which preserve the quality of life of the exposed as well as enabling the individual the "acceptance of self" (R. Guardini). PMID- 26906531 TI - [Bavarian Centre for Health: Health-related Prevention - Pragmatic and Need oriented]. AB - The idea of improving population health by means of collective action and prevention of diseases in 1973 resulted in the decision of the Bavarian Parliament to establish a "Bavarian Centre for Health Education". According to its statutes, the aim was to promote the cooperation between institutions and organizations working in the field of public health and health education in Bavaria and to make their efforts effective by information, organization and coordination. The work of the 1970s and 80s was largely based on risk factor model, using methods of information and deterrence. The findings of salutogenesis led to changes in the methods of disease prevention and health education in the early 1990s, health promotion was established, new approaches and new subjects were added. The renaming of "Bavarian Centre for Health Education" to "Bavarian Centre for Health" represents the change in the underlying concept of health. This paper traces the development until today. PMID- 26906532 TI - [From the MONICA-project via KORA to the NAKO-study: Practical Utility of Epidemiological Studies in Augsburg Region]. AB - The objective of the WHO-MONICA study was to determine the influence of changing risk factors and treatment options on myocardial infarction rates in populations in a 10-year time period. For this purpose, a population-based myocardial infarction registry was established in 1984 in Augsburg (covering the city of Augsburg and 2 adjacent counties) in order to continuously register all inhabitants of the region who had a myocardial infarction during the study period. In addition, three cross-sectional studies based on random population samples (1984/85, 1989/90 and 1994/95) were carried out. Our data revealed a continuous decrease of myocardial infarction incidence and demonstrated that the decrease of coronary mortality can be ascribed to decreasing myocardial infarction incidence and longer survival after myocardial infarction. Until today the myocardial infarction registry continues to be a permanent part of the Cooperative Health Research in the Region of Augsburg (KORA). Moreover, within the framework of KORA, a fourth population-based cross-sectional study was carried out in 1999/2001. Meanwhile, more than 18 000 study participants have been followed-up for specific endpoints for up to 30 years. A large number of publications, which address cardiovascular diseases, type 2 diabetes mellitus, lung diseases, environmental and genetic questions, health services research and numerous other topics, are based on the KORA study. Today we know that the development of chronic diseases can be ascribed to a complex interaction of social factors, health policy conditions, health behavior, risk factors and molecular mechanisms. To tackle the challenges posed by these multiple factors in Germany, NAKO (Nationale Kohorte), the largest nation-wide long-term study so far, was initiated. Within the framework of the NAKO study, 200 000 persons aged between 20 and 69 years in Germany - thereof 20 000 persons in the region of Augsburg - will be examined and interviewed in the next 10 years, and widespread diseases will be investigated with modern epidemiological methods. The results of these epidemiological long-term studies will contribute to the prevention, early diagnosis and best possible treatment of widespread diseases. PMID- 26906533 TI - [Contribution of Health Care Research to Establishing Social Equality in Health and Health Care Opportunities]. AB - Social inequalities in health and health care services represent issues of major concern. Findings in this area reveal inequalities in health and health care indicating disadvantages for individuals with a low socioeconomic background. Although the health care system plays a marginal role in the explanation of inequalities in health, health services research can be an important part in the development of equal health opportunities. The current article describes the causal associations between social inequalities, health inequalities and the health care service. Health services research can make a contribution to increasing equal opportunities in health and health care service. Against this background, we discuss the existing potential and need of research in the area of health services. PMID- 26906534 TI - [Why Strive after Clinical Social Medicine? From Epidemiological Association to Personalized Social Medicine: a Case of Breast Cancer Care]. AB - Advances in biomedicine, especially molecular biology and genetics, gave rise to the concept of personalized medicine targeting the patient's individual characteristics and needs to ensure the best possible therapy and healthcare. This concept, however, can be successfully implemented only if due consideration is given to (psycho-)social factors, as is shown for instance by considerably reduced post-therapy survival rates among cancer patients in regions with lower socioeconomic status, How breast cancer patients, for instance, find their way back to daily life and work after initial treatment at a breast center is substantially determined by multiple factors going beyond pure medical care. These factors critically affect health status and therapy outcomes, but are missing in current research agenda. A profound expertise in social medicine is required to respond in ways tailored to the individual's healthcare needs that go beyond just medical therapy. This expertise comprises, in particular, knowledge of inequality of access to healthcare due to varying health competence that in turn, results in inequality of health outcome and care. Competence in social medicine both in the clinic and outpatient care can help to individually target negative factors that originate from the social environment as well as from deficits in communication and coordination in the healthcare system and have an effect on the health status of patients..This, however, requires institutionalization of (clinical) social medicine and in particular, better opportunities for advanced training in social medicine in clinical departments and outpatient units. PMID- 26906535 TI - [Motivation for Prevention in Childhood as a Basis for long-Term Dental Health: The Augsburg Model]. AB - Oral health promotion programs have been shown to be more effective the earlier they are started. In the city of Augsburg, the activities of the School Dental Service were replaced by a cooperation model in 2001, which provides a reasonable combination of group and individual dental prophylaxis. Three epidemiological evaluations show continuously increasing rates of natural healthy primary teeth in preschool children of all population groups. The Augsburg cooperation model "child and youth dental health" represents a practice-oriented approach in accordance with the new German prevention law. PMID- 26906536 TI - [Medical Care for Homeless People - Individual Right and a Social Duty for an Inclusive Society]. AB - Homelessness is a social phenomenon of increasing frequency in Germany and of high relevance for an inclusive society. Its expression is both caused psychosocially and moderated socioeconomically, often with negatively reinforcing feedback-loops. This overview describes health effects and strategies for improvement, using the example of the "Mainzer Modell". The comprehensive availability of adequate medical care are both an individual right and a social duty for an inclusive society. PMID- 26906537 TI - [Development of Social Medicine and Public Health in Germany]. AB - Social medicine in Germany has multiple lines of tradition, which are marked by the presence of 2 German states and their re-unification and by the (re )establishment of multidisciplinary public health by the end of the twentieth century. At the same time, a differentiation within the applied fields of social medicine into several thematic topics can be observed. These can be grouped in a first step into the domains of clinical social medicine, of social medicine for social insurance purposes and of a population-oriented social medicine. For social medicine as a scientific discipline within the broad context of medicine, the requirement of a context-adequate development, which encompasses the special methods of multidisciplinary public health, poses big challenges. For successfully meeting these challenges and going beyond population-oriented public health and for bridging the gap between the individual and the social medical institutions of the health system, it is indispensable for social medicine to be independent of other disciplines within the array of medical specialties. The present study argues for strengthening social medicine within the medical faculties. Chairs for social medicine and public health are not only in the interest of the applied fields of social medicine, but represent also an indispensable scientific discipline which can relate and contribute to all specialties of medicine. PMID- 26906538 TI - [DGSMP - Interdisciplinarity to Advance Social Medicine and Prevention of Illness]. AB - The German Society for Social Medicine and Prevention (DGSMP) refers back to a tradition of over more than 100 years, nevertheless having a critical look at it. As a scientific medical society the DGSMP promotes cross-sectoral configuration of contemporary social medicine to the benefit of both, general welfare and individual health in form of prevention, rehabilitation, re-integration, palliation and long-term care. Human medicine is the lead discipline in the interdisciplinary approach by the DGSMP in order to create - facing the dynamics in the health care system - professional prerequisites to maintain and update solidarity and equity in medical services on a scientific basis. PMID- 26906539 TI - [A Contribution to the Current Debate on Public and Global Health in Germany]. AB - In June 2015 the German Academies of Science and Technology published a report on the structures, developments and challenges in the field of public and global health in Germany. Its call for a strengthening of public and global health in Germany was well received among researchers and practitioners in the field. At the same time criticism arose. Key controversies relate to the future institutional set-up of public and global health research in Germany, the consideration of the social determinants of health versus biomedical and technological approaches, the need for further research versus the need for political implementation of what is already known, and the consideration of the political context, such as intellectual property rights. This contribution provides an overview on the debate and lays down the perspective of the German Medical Students' Association (bvmd) and the Globalisation and Health Initiative (GandHI), putting forward demands regarding the role of public and global health in medical education in Germany. PMID- 26906540 TI - [Not Available]. PMID- 26906541 TI - [Not Available]. PMID- 26906542 TI - [Not Available]. PMID- 26906543 TI - Insights into the mechanism of human papillomavirus E2-induced procaspase-8 activation and cell death. AB - High-risk human papillomavirus (HR-HPV) E2 protein, the master regulator of viral life cycle, induces apoptosis of host cell that is independent of its virus associated regulatory functions. E2 protein of HR-HPV18 has been found to be involved in novel FADD-independent activation of caspase-8, however, the molecular basis of this unique non-death-fold E2-mediated apoptosis is poorly understood. Here, with an interdisciplinary approach that involves in silico, mutational, biochemical and biophysical probes, we dissected and characterized the E2-procasapse-8 binding interface. Our data demonstrate direct non-homotypic interaction of HPV18 E2 transactivation domain (TAD) with alpha2/alpha5 helices of procaspase-8 death effector domain-B (DED-B). The observed interaction mimics the homotypic DED-DED complexes, wherein the conserved hydrophobic motif of procaspase-8 DED-B (F122/L123) occupies a groove between alpha2/alpha3 helices of E2 TAD. This interaction possibly drives DED oligomerization leading to caspase-8 activation and subsequent cell death. Furthermore, our data establish a model for E2-induced apoptosis in HR-HPV types and provide important clues for designing E2 analogs that might modulate procaspase-8 activation and hence apoptosis. PMID- 26906544 TI - PXR- and CAR-mediated herbal effect on human diseases. AB - The pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are two members of the nuclear receptor superfamily that regulate a broad range of genes involved in drug metabolism and transport. A variety of naturally occurring compounds present in herbal medicines were identified as ligands of PXR and CAR. Recently, accumulative evidences have revealed the PXR- and CAR-mediated herbal effect against multiple human diseases, including inflammatory bowel disease (IBD), cholestatic liver disease, and jaundice. The current review summarized the recent progress in identifying the expanding libraries of herbal medicine as ligands for PXR and CAR. Moreover, the potential for herbal medicines as promising therapeutic agents which were mainly regulated through PXR/CAR signaling pathways was also discussed. The discovery of herbal medicines as modulators of PXR and CAR, and their PXR- and CAR-mediated effect on human diseases will provide a basis for rational drug design, and eventually be explored as a novel therapeutic approach against human diseases. This article is part of a Special Issue entitled: Xenobiotic nuclear receptors: New Tricks for An Old Dog, edited by Dr. Wen Xie. PMID- 26906545 TI - METCAM/MUC18 is a novel tumor and metastasis suppressor for the human ovarian cancer SKOV3 cells. AB - BACKGROUND: Increased expression of METCAM/MUC18, a trans-membrane cell adhesion molecule in the Ig-like gene superfamily, has been associated with the malignant progression of epithelial ovarian carcinomas. To investigate if this is a fortuitous correlation or if METCAM/MUC18 actually plays a role in the progression of the cancer, we tested effects of enforced expression of METCAM/MUC18 on in vitro behaviors, in vivo tumorigenesis, and in vivo malignant progression of human ovarian cancer SK-OV-3 cells, which minimally expressed this protein. METHODS: For in vitro and in vivo tests, we transfected human METCAM/MUC18 cDNA gene into SK-OV-3 cells in a mammalian expression vector pcDNA3.1+ and obtained G418-resistant (G418(R)) clones, which expressed various levels of human METCAM/MUC18. To mimic physiological situations, we used pooled METCAM/MUC18-expressing and control (vector) clones for testing effects of human METCAM/MUC18 over-expression on in vitro motility and invasiveness, and on in vivo tumor formation and metastasis in female athymic nude mice. Effects of METCAM/MUC18 on the expression of various downstream key factors related to tumorigenesis were also evaluated by Western blot analyses. RESULTS: The over expression of METCAM/MUC18 inhibited in vitro motility and invasiveness of SK-OV 3 cells. SK-OV-3 cells of the control (vector) clone (3D), which did not express human METCAM/MUC18, supported the formation of a solid tumor after SC injection of the cells at dorsal or ventral sites and also formation of solid tumor and ascites after IP injection in the intraperitoneal cavity of nude mice. In contrast, SK-OV-3 cells from the METCAM/MUC18-expressing clone (2D), which expressed a high level of METCAM/MUC18, did not support the formation of a solid tumor at SC sites, or formation of ascites in the intraperitoneal cavity of nude mice. Expression levels of downstream key factors, which may affect tumor proliferation and angiogenesis, were reduced in tumors induced by the METCAM/MUC18-expressing clone (2D). CONCLUSIONS: We conclude that increased human METCAM/MUC18 expression in ovarian cancer SK-OV-3 cells suppressed tumorigenesis and ascites formation in nude mice, suggesting that human METCAM/MUC18 plays a suppressor role in the progression of ovarian cancer, perhaps by reducing proliferation and angiogenesis. PMID- 26906546 TI - The Emergency Physician's Role in Differentiating Brugada Syndrome from Brugada Phenotype. PMID- 26906547 TI - Brugada Phenocopy or Unmasked Brugada Syndrome? Relevance of the Provocation Test. PMID- 26906549 TI - AMP-activated protein kinase and its multifaceted regulation of hepatic metabolism. AB - PURPOSE OF REVIEW: The current review summarizes recent advancements in our mechanistic and physiological understanding of the energy sensing AMP-activated protein kinase (AMPK) and its regulation of select aspects of hepatic metabolism. RECENT FINDINGS: A highly conserved serine/threonine kinase, AMPK governs a multitude of cellular process to activate catabolic and inhibit anabolic pathways. Recent work has provided clarity as to the importance and contribution of the AMPK signaling cascade to various aspects of cellular metabolism, including lipid homeostasis, hepatic glucose production, mitochondrial metabolism, and autophagy. SUMMARY: With more than 60 confirmed substrates, the physiological significance of AMPK signaling has been difficult to ascertain. The generation of targeted knock-in mutations on key AMPK substrates has begun to shed light on this complex system. Future studies are needed to further decipher the complexity, significance, and potential therapeutic targeting of hepatic AMPK signaling. PMID- 26906550 TI - Urgent action on UK air pollution is needed, say experts. PMID- 26906548 TI - Systematic Evolution and Study of UAGN Decoding tRNAs in a Genomically Recoded Bacteria. AB - We report the first systematic evolution and study of tRNA variants that are able to read a set of UAGN (N = A, G, U, C) codons in a genomically recoded E. coli strain that lacks any endogenous in-frame UAGN sequences and release factor 1. Through randomizing bases in anticodon stem-loop followed by a functional selection, we identified tRNA mutants with significantly improved UAGN decoding efficiency, which will augment the current efforts on genetic code expansion through quadruplet decoding. We found that an extended anticodon loop with an extra nucleotide was required for a detectable efficiency in UAGN decoding. We also observed that this crucial extra nucleotide was converged to a U (position 33.5) in all of the top tRNA hits no matter which UAGN codon they suppress. The insertion of U33.5 in the anticodon loop likely causes tRNA distortion and affects anticodon-codon interaction, which induces +1 frameshift in the P site of ribosome. A new model was proposed to explain the observed features of UAGN decoding. Overall, our findings elevate our understanding of the +1 frameshift mechanism and provide a useful guidance for further efforts on the genetic code expansion using a non-canonical quadruplet reading frame. PMID- 26906551 TI - Pre-diagnostic serum levels of EGFR and ErbB2 and genetic glioma risk variants: a nested case-control study. AB - Genetic variants have been associated with the risk of developing glioma, but functional mechanisms on disease phenotypic traits remain to be investigated. One phenotypic trait of glioblastoma is the mutation and amplification of the epidermal growth factor receptor (EGFR) gene. We investigated associations between pre-diagnostic serum protein concentrations of EGFR and ErbB2, both members of the EGFR family, and future risk of glioma. Further, we studied if EGFR glioma risk variants were associated with EGFR and ErbB2 serum levels. We assessed the associations between genetic glioma risk variants and serum concentrations of EGFR and ErbB2, as measured in pre-diagnostic cohort serum samples of 593 glioma patients and 590 matched cancer-free controls. High serum EGFR and ErbB2 levels were associated with risk of developing glioblastoma (P = 0.008; OR = 1.58, 95 % CI = 1.13-2.22 and P = 0.017, OR = 1.63, 95 % CI = 1.09 2.44, respectively). High serum ErbB2 concentration was also associated with glioma risk overall (P = 0.049; OR = 1.39, 95 % CI = 1.00-1.93). Glioma risk variants were not associated with high serum protein abundance. In contrast, the EGFR risk variant rs4947986 (T) was correlated with decreased EGFR serum levels (study cohort P = 0.024 and controls P = 0.009). To our knowledge, this is the first study showing an association of EGFR and ErbB2 serum levels with glioma more than a decade before diagnosis, indicating that EGFR and ErbB2 serum proteins are important in early gliomagenesis. However, we did not find evidence that glioma risk variants were associated with high pre-diagnostic serum concentrations of EGFR and ErbB2. PMID- 26906552 TI - CIZ1 interacts with YAP and activates its transcriptional activity in hepatocellular carcinoma cells. AB - Dysregulation of Hippo-Yes-associate protein (YAP) signaling has important roles in the tumorigenesis of hepatocellular carcinoma (HCC). Our previous studies have shown that Cip1 interacting zinc finger protein 1 (CIZ1) activated YAP signaling in the HCC cells and promoted the growth and migration of cancer cells. However, the mechanisms for the activation of YAP signaling by CIZ1 are unknown. In this study, it was found that CIZ1 interacted with the transcriptional factor YAP in HCC cells. The nuclear matrix anchor domain of CIZ1 is responsible for its interaction with YAP. Moreover, CIZ1 enhanced the interaction between YAP and TEAD. Knocking down the expression of CIZ1 impaired the transcriptional activity as well as the biological functions of YAP. Taken together, our study demonstrated that CIZ1 is a positive regulator of YAP signaling, and CIZ1 might be a therapeutic target for HCC. PMID- 26906553 TI - Thalidomide treatment for patients with previously untreated multiple myeloma: a meta-analysis of randomized controlled trials. AB - The efficacy and safety of thalidomide as an initial treatment in myeloma patients who were unsuitable for autologous stem cell transplantation (ASCT), as induction treatment prior to ASCT, or as a maintenance treatment was unclear. The purpose of this study was to assess the benefits and risks of thalidomide for previously untreated myeloma patients. MEDLINE, EMBASE, and Cochrane Library were searched for randomized controlled trials (RCTs) of thalidomide used in either induction or maintenance therapy for previously untreated myeloma patients. Twenty-two RCTs enrolling 9098 patients were identified, including 15 RCTs of induction thalidomide, 6 RCTs of maintenance thalidomide, and 1 RCT of induction and maintenance thalidomide. Induction thalidomide improved overall response rate (ORR) (risk ratio (RR) 1.54, 95 % confidence interval (CI) 1.30-1.83), complete response rate (CRR) (RR 3.03, 95 % CI 1.91-4.80), progression-free survival (PFS) (hazard ratio (HR) 0.65, 95 % CI 0.56-0.76), and overall survival (OS) (HR 0.78, 95 % CI 0.67-0.91) in patients who were not allowed to receive ASCT. Induction thalidomide improved pre-ASCT ORR (RR 1.20, 95 % CI 1.11-1.30), pre-ASCT and post ASCT CRR (RR 1.47, 95 % CI 1.12-1.93 and RR 1.23, 95 % CI 1.00-1.50, respectively), and PFS (HR 0.73, 95 % CI 0.59-0.91) in patients who were allowed to receive ASCT, but it did not improve post-ASCT ORR (RR 1.04, 95 % CI 0.99 1.09) and OS (HR 0.91, 95 % CI 0.79-1.05). Improved PFS and prolonged OS were observed (HR 0.61, 95 % CI 0.53-0.70 and HR 0.77, 95 % CI 0.62-0.95, respectively) when thalidomide was added to maintenance therapy. More patients experienced venous thromboembolism (VTE) of grade 3/4 when thalidomide was added to induction or maintenance therapy (HR 2.15, 95 % CI 1.58-2.92 and RR 1.96, 95 % CI 1.13-3.40, respectively). Induction thalidomide still increased the risk of VTE (RR 1.53, 95 % CI 1.12-2.08) after VTE prophylaxis was used. Induction thalidomide effectively improved CRR, ORR, and PFS (except post-ASCT ORR). Notably, induction thalidomide improved OS in patients who were not allowed to receive ASCT but not in patients who were allowed to receive ASCT. The addition of thalidomide to maintenance therapy improved both PFS and OS. However, thalidomide led to a greater risk of VTE with grade 3/4. This risk did not disappear after VTE prophylaxis was used in induction therapy with thalidomide. PMID- 26906554 TI - 3D printing provides unrivalled bespoke teaching tools for autologous free flap breast reconstruction. PMID- 26906555 TI - Re: A simplified approach to reconstruction of hemipelvectomy defects with lower extremity free fillet flaps to minimize ischaemia time. PMID- 26906556 TI - Fragility, uncertainty, and healthcare. AB - Medicine seeks to overcome one of the most fundamental fragilities of being human, the fragility of good health. No matter how robust our current state of health, we are inevitably susceptible to future illness and disease, while current disease serves to remind us of various frailties inherent in the human condition. This article examines the relationship between fragility and uncertainty with regard to health, and argues that there are reasons to accept rather than deny at least some forms of uncertainty. In situations of current ill health, both patients and doctors seek to manage this fragility through diagnoses that explain suffering and provide some certainty about prognosis as well as treatment. However, both diagnosis and prognosis are inevitably uncertain to some degree, leading to questions about how much uncertainty health professionals should disclose, and how to manage when diagnosis is elusive, leaving patients in uncertainty. We argue that patients can benefit when they are able to acknowledge, and appropriately accept, some uncertainty. Healthy people may seek to protect the fragility of their good health by undertaking preventative measures including various tests and screenings. However, these attempts to secure oneself against the onset of biological fragility can cause harm by creating rather than eliminating uncertainty. Finally, we argue that there are good reasons for accepting the fragility of health, along with the associated uncertainties. PMID- 26906557 TI - Dependence and a Kantian conception of dignity as a value. AB - Kantian moral concepts concerning respect for human dignity have played a central role in articulating ethical guidelines for medical practice and research, and for articulating some central positions within bioethical debates more generally. The most common of these Kantian moral concepts is the obligation to respect the dignity of patients and of human research subjects as autonomous, self determining individuals. This article describes Kant's conceptual distinction between dignity and autonomy as values, and draws on the work of several contemporary Kantian philosophers who employ the distinction to make sense of some common moral intuitions, feelings, and norms. Drawing on this work, the article argues that the conceptual distinction between dignity and autonomy as values is indispensable in the context of considering our obligations to those who are dependent and vulnerable. PMID- 26906559 TI - Functional analysis of two genes coding for distinct cation diffusion facilitators of the ectomycorrhizal Zn-accumulating fungus Russula atropurpurea. AB - Russula atropurpurea can accumulate remarkably high concentrations of Zn in its sporocarps. We have previously demonstrated that 40 % of the intracellular Zn in this species is sequestered by MT-like RaZBP peptides. To see what other mechanisms for the handling of the accumulated Zn are available to R. atropurpurea, we searched its transcriptome for cDNAs coding for transporters of the cation diffusion facilitator (CDF) family. The transcriptome search enabled us to identify RaCDF1 and RaCDF2, which were further subjected to functional studies in metal sensitive Saccharomyces cerevisiae. The expression of RaCDF1 and its translational fusion with green fluorescent protein (GFP) protected the yeasts against Zn and Co, but not Cd or Mn, toxicity and led to increased Zn accumulation in the cells. The GFP fluorescence, observed in the RaCDF1::GFP expressing yeasts on tonoplasts, indicated that the RaCDF1-mediated Zn and Co tolerance was a result of vacuolar sequestration of the metals. The expression of RaCDF2 supported Zn, but not Mn, tolerance in the yeasts and reduced the cellular uptake of Zn, which is congruent with the proposed idea of the Zn-efflux function of RaCDF2, supported by the localization of GFP-derived fluorescence on the plasma membrane of the yeasts expressing functional RaCDF2::GFP. Contrarily, RaCDF2 increased the sensitivity to Co and Cd in the yeasts and significantly promoted Cd uptake, which suggested that it can act as a bidirectional metal transporter. The notion that RaCDF1 and RaCDF2 are genuine CDF transporters in R. atropurputrea was further reinforced by the fact that the RaCDF-associated metal tolerance and uptake phenotypes were lost upon the replacement of histidyl (in RaCDF1) and aspartyl (in RaCDF2), which are highly conserved in the second transmembrane domain and known to be essential for the function of CDF proteins. PMID- 26906558 TI - Pyruvate Carboxylase Activates the RIG-I-like Receptor-Mediated Antiviral Immune Response by Targeting the MAVS signalosome. AB - When retinoic acid-inducible gene 1 protein (RIG-I)-like receptors sense viral dsRNA in the cytosol, RIG-I and melanoma differentiation-associated gene 5 (MDA5) are recruited to the mitochondria to interact with mitochondrial antiviral signaling protein (MAVS) and initiate antiviral immune responses. In this study, we demonstrate that the biotin-containing enzyme pyruvate carboxylase (PC) plays an essential role in the virus-triggered activation of nuclear factor kappa B (NF kappaB) signaling mediated by MAVS. PC contributes to the enhanced production of type I interferons (IFNs) and pro-inflammatory cytokines, and PC knockdown inhibits the virus-triggered innate immune response. In addition, PC shows extensive antiviral activity against RNA viruses, including influenza A virus (IAV), human enterovirus 71 (EV71), and vesicular stomatitis virus (VSV). Furthermore, PC mediates antiviral action by targeting the MAVS signalosome and induces IFNs and pro-inflammatory cytokines by promoting phosphorylation of NF kappaB inhibitor-alpha (IkappaBalpha) and the IkappaB kinase (IKK) complex, as well as NF-kappaB nuclear translocation, which leads to activation of interferon stimulated genes (ISGs), including double-stranded RNA-dependent protein kinase (PKR) and myxovirus resistance protein 1 (Mx1). Our findings suggest that PC is an important player in host antiviral signaling. PMID- 26906560 TI - HmuS and HmuQ of Ensifer/Sinorhizobium meliloti degrade heme in vitro and participate in heme metabolism in vivo. AB - Ensifer meliloti is a nitrogen-fixing symbiont of the alfalfa legume able to use heme as an iron source. The transport mechanism involved in heme acquisition in E. meliloti has been identified and characterized, but the fate of heme once inside the cell is not known. In silico analysis of E. meliloti 1021 genome revealed no canonical heme oxygenases although two genes encoding putative heme degrading enzymes, smc01518 and hmuS, were identified. SMc01518 is similar to HmuQ of Bradyrhizobium japonicum, which is weakly homologous to the Staphylococcus aureus IsdG heme-degrading monooxygenase, whereas HmuS is homolog to Pseudomonas aeruginosa PhuS, a protein reported as a heme chaperone and as a heme degrading enzyme. Recombinant HmuQ and HmuS were able to bind hemin with a 1:1 stoichiometry and displayed a Kd value of 5 and 4 uM, respectively. HmuS degrades heme in vitro to the biliverdin isomers IX-beta and IX-delta in an equimolar ratio. The HmuQ recombinant protein degrades heme to biliverdin IX delta only. Additionally, in this work we demonstrate that humS and hmuQ gene expression is regulated by iron and heme in a RirA dependent manner and that both proteins are involved in heme metabolism in E. meliloti in vivo. PMID- 26906561 TI - Cost-effectiveness thresholds in health care: a bookshelf guide to their meaning and use. AB - There is misunderstanding about both the meaning and the role of cost effectiveness thresholds in policy decision making. This article dissects the main issues by use of a bookshelf metaphor. Its main conclusions are as follows: it must be possible to compare interventions in terms of their impact on a common measure of health; mere effectiveness is not a persuasive case for inclusion in public insurance plans; public health advocates need to address issues of relative effectiveness; a 'first best' benchmark or threshold ratio of health gain to expenditure identifies the least effective intervention that should be included in a public insurance plan; the reciprocal of this ratio - the 'first best' cost-effectiveness threshold - will rise or fall as the health budget rises or falls (ceteris paribus); setting thresholds too high or too low costs lives; failure to set any cost-effectiveness threshold at all also involves avertable deaths and morbidity; the threshold cannot be set independently of the health budget; the threshold can be approached from either the demand side or the supply side - the two are equivalent only in a health-maximising equilibrium; the supply side approach generates an estimate of a 'second best' cost-effectiveness threshold that is higher than the 'first best'; the second best threshold is the one generally to be preferred in decisions about adding or subtracting interventions in an established public insurance package; multiple thresholds are implied by systems having distinct and separable health budgets; disinvestment involves eliminating effective technologies from the insured bundle; differential weighting of beneficiaries' health gains may affect the threshold; anonymity and identity are factors that may affect the interpretation of the threshold; the true opportunity cost of health care in a community, where the effectiveness of interventions is determined by their impact on health, is not to be measured in money - but in health itself. PMID- 26906562 TI - Optimization of bacterial cellulose production by Gluconacetobacter xylinus using carob and haricot bean. AB - Bacterial cellulose (BC) can be used in medical, biomedical, electronic, food, and paper industries because of its unique properties distinguishing it from plant cellulose. BC production was statistically optimized by Gluconacetobacter xylinus strain using carob and haricot bean (CHb) medium. Eight parameters were evaluated by Plackett-Burman Design and significant three parameters were optimized by Central Composite Design. Optimal conditions for production of BC in static culture were found as: 2.5g/L carbon source, 2.75g/L protein source, 9.3% inoculum ratio, 1.15g/L citric acid, 2.7g/L Na2HPO4, 30 degrees C incubation temperature, 5.5 initial pH, and 9days of incubation. This study reveals that BC production can be carried out using carob and haricot bean extracts as carbon and nitrogen sources, and CHb medium has higher buffering capacity compared to Hestrin and Schramm media. Model obtained from this study is used to predict and optimize BC production yield using CHb medium. PMID- 26906563 TI - Fully Hydrogenated Beryllium Nanoclusters. AB - We present the ground state and energetically low structures of BenH2n nanoclusters as predicted using density functional theory (DFT) and employing the M06 meta-hybrid exchange-correlation functional. Results using the M06 functional are benchmarked against high accuracy coupled-cluster CCSD(T) and found to be in excellent agreement. For small values of n, the linear or polymeric form is the lowest energy geometry, while for sizes larger, n > 9 ring type and link type structures are the energetically lowest configurations. This trend has also been observed through ab initio molecular dynamics (AIMD) simulations at finite temperatures. In addition to the binding energies of the structures we report on polymerization energies, Be-H bond energies with respect to coordination details, hydrogen desorption energies of saturated and oversaturated species, as well as computed infrared spectra of all the ground state and energetically low lying structures presented. Furthermore, we find that the saturated polymeric forms of the nanoclusters cannot retain molecular hydrogen, in contrast to what is expected when zero point energy corrections are not taken into account. PMID- 26906564 TI - Spacer Length: A Determining Factor in the Design of Galactosyl Ligands for Hepatoma Cell-Specific Liposomal Gene Delivery. AB - BACKGROUND: Use of nucleic acids to treat acquired or inherited hepatic diseases has considerable potential. Although recombinant viruses are popular vectors, interest in cheaper, often less immunogenic, non-viral modalities, is increasing. Thus hepatotropic, galactosylated lipoplexes directed to the hepatic asialoglycoprotein receptor (ASGP-R) are promising candidates. OBJECTIVE: Here we examine the effect that galactosyl ligand spacer length has on the transfection activity of ASGP-Rtargeted lipoplexes in the human hepatoma cell line HepG2. METHODS: Galactosyl ligands with spacer lengths in the range 2.4-24.1 A were prepared and formulated into lipoplexes that were characterized by cryo-TEM, band shift, dye displacement and nuclease digestion assays. Cytotoxicity and transfection profiles were determined in liver-derived HepG2 cells and the renal ASGP-R-negative HEK293 line. RESULTS: Lipoplexes, which formed at endpoint +/- charge ratios in the range 1:1-3:1, accorded cargo DNA good protection from serum nuclease digestion and were well-tolerated by both cell lines. Transfection activities in the hepatoma cell line decreased markedly in the presence of a competing ASGP-R cognate ligand and also as the ligand spacer length increased, while activities in HEK293 cells were significantly lower (P <0.05-0.001). CONCLUSION: Targeted lipoplexes enter HepG2 cells by receptor mediation and the uptake of transfecting complexes and those displaying more rigid short and medium length spacers is more efficient. This observation will inform the design of hepatotropic lipoplexes that are suitable for applications in vivo. PMID- 26906565 TI - Cytosolic sulfotransferase 1A1 regulates HIV-1 minus-strand DNA elongation in primary human monocyte-derived macrophages. AB - BACKGROUND: The cellular sulfonation pathway modulates key steps of virus replication. This pathway comprises two main families of sulfonate-conjugating enzymes: Golgi sulfotransferases, which sulfonate proteins, glycoproteins, glycolipids and proteoglycans; and cytosolic sulfotransferases (SULTs), which sulfonate various small molecules including hormones, neurotransmitters, and xenobiotics. Sulfonation controls the functions of numerous cellular factors such as those involved in cell-cell interactions, cell signaling, and small molecule detoxification. We previously showed that the cellular sulfonation pathway regulates HIV-1 gene expression and reactivation from latency. Here we show that a specific cellular sulfotransferase can regulate HIV-1 replication in primary human monocyte-derived macrophages (MDMs) by yet another mechanism, namely reverse transcription. METHODS: MDMs were derived from monocytes isolated from donor peripheral blood mononuclear cells (PBMCs) obtained from the San Diego Blood Bank. After one week in vitro cell culture under macrophage-polarizing conditions, MDMs were transfected with sulfotranserase-specific or control siRNAs and infected with HIV-1 or SIV constructs expressing a luciferase reporter. Infection levels were subsequently monitored by luminescence. Western blotting was used to assay siRNA knockdown and viral protein levels, and qPCR was used to measure viral RNA and DNA products. RESULTS: We demonstrate that the cytosolic sulfotransferase SULT1A1 is highly expressed in primary human MDMs, and through siRNA knockdown experiments, we show that this enzyme promotes infection of MDMs by single cycle VSV-G pseudotyped human HIV-1 and simian immunodeficiency virus vectors and by replication-competent HIV-1. Quantitative PCR analysis revealed that SULT1A1 affects HIV-1 replication in MDMs by modulating the kinetics of minus-strand DNA elongation during reverse transcription. CONCLUSIONS: These studies have identified SULT1A1 as a cellular regulator of HIV-1 reverse transcription in primary human MDMs. The normal substrates of this enzyme are small phenolic-like molecules, raising the possibility that one or more of these substrates may be involved. Targeting SULT1A1 and/or its substrate(s) may offer a novel host-directed strategy to improve HIV-1 therapeutics. PMID- 26906566 TI - Constraining OCT with Knowledge of Device Design Enables High Accuracy Hemodynamic Assessment of Endovascular Implants. AB - BACKGROUND: Stacking cross-sectional intravascular images permits three dimensional rendering of endovascular implants, yet introduces between-frame uncertainties that limit characterization of device placement and the hemodynamic microenvironment. In a porcine coronary stent model, we demonstrate enhanced OCT reconstruction with preservation of between-frame features through fusion with angiography and a priori knowledge of stent design. METHODS AND RESULTS: Strut positions were extracted from sequential OCT frames. Reconstruction with standard interpolation generated discontinuous stent structures. By computationally constraining interpolation to known stent skeletons fitted to 3D 'clouds' of OCT Angio-derived struts, implant anatomy was resolved, accurately rendering features from implant diameter and curvature (n = 1 vessels, r2 = 0.91, 0.90, respectively) to individual strut-wall configurations (average displacement error ~15 MUm). This framework facilitated hemodynamic simulation (n = 1 vessel), showing the critical importance of accurate anatomic rendering in characterizing both quantitative and basic qualitative flow patterns. Discontinuities with standard approaches systematically introduced noise and bias, poorly capturing regional flow effects. In contrast, the enhanced method preserved multi-scale (local strut to regional stent) flow interactions, demonstrating the impact of regional contexts in defining the hemodynamic consequence of local deployment errors. CONCLUSION: Fusion of planar angiography and knowledge of device design permits enhanced OCT image analysis of in situ tissue-device interactions. Given emerging interests in simulation-derived hemodynamic assessment as surrogate measures of biological risk, such fused modalities offer a new window into patient-specific implant environments. PMID- 26906568 TI - Experimental dynamic deformation analysis of active stressed lap. AB - We introduce a method to measure the dynamic surface deformation of an active stressed lap for fabricating a 4 mf/1.5 mirror. Lap surface accuracy working in some typical deformation velocities is put forward. Experimental results indicate that dynamic lap surface accuracy is worse than that of a static surface, and dynamic surface accuracy gets worse if deformation velocity increases, while the difference of lap surface error RMS is less than 1 MUm. An optimization of the processing strategy is feasible through changing the deformation velocity of the active stressed lap depending on the processing schedule. After optimizing the grinding and polishing strategy, efficiency is expected to have a significant increase. PMID- 26906569 TI - Effects of annealing temperature on optical, morphological, and electrical characteristics of polyfluorene-derivative thin films on ITO glass substrate. AB - The effects of postdeposition annealing temperature (125 degrees C-200 degrees C) toward optical, morphological, and electrical characteristics of poly[(9,9 dioctylfluorenyl-2,7-diyl)-co-(1,4-phenylene)] end capped with dimethylphenyl group deposited on indium tin oxide glass substrates were investigated. Green and red-infrared photoluminescence emissions, originating from P-conjugation aggregates and keto-type defects did not attenuate the intensity of the blue emission peak. This suggested that the aggregates and defects might serve as local traps for radiative recombination. In samples annealed at 125 degrees C-175 degrees C, a decreasing optical energy gap (E(g)) that decreased barrier height as well as an increasing amount of traps have increased current conduction via thermionic emission and trap-assisted tunneling. Nonetheless, an acquisition of the largest E(g) and amount of traps testified that thermionic emission was dominating current conduction, surpassing trap-assisted tunneling in samples annealed at 200 degrees C. PMID- 26906570 TI - Radiative transfer simulations of the two-dimensional ocean glint reflectance and determination of the sea surface roughness. AB - An optimized discrete-ordinate radiative transfer model (DISORT3) with a pseudo two-dimensional bidirectional reflectance distribution function (BRDF) is used to simulate and validate ocean glint reflectances at an infrared wavelength (1036 nm) by matching model results with a complete set of BRDF measurements obtained from the NASA cloud absorption radiometer (CAR) deployed on an aircraft. The surface roughness is then obtained through a retrieval algorithm and is used to extend the simulation into the visible spectral range where diffuse reflectance becomes important. In general, the simulated reflectances and surface roughness information are in good agreement with the measurements, and the diffuse reflectance in the visible, ignored in current glint algorithms, is shown to be important. The successful implementation of this new treatment of ocean glint reflectance and surface roughness in DISORT3 will help improve glint correction algorithms in current and future ocean color remote sensing applications. PMID- 26906567 TI - Hypoxia-Related Marker GLUT-1, CAIX, Proliferative Index and Microvessel Density in Canine Oral Malignant Neoplasia. AB - For various types of tumor therapy, it is suggested that co-targeting of tumor microenvironment, mainly tumor vasculature, mediates tumor response mechanisms. Immunohistochemistry for glucose transporter-1 (GLUT-1), carbonic anhydrase-IX (CAIX), Ki-67, and von Willebrand factor VIII for microvessel density (MVD) were performed on formalin-fixed paraffin-embedded samples of canine oral malignant neoplasms. Polarographic oxygen measurements (median pO2) and perfusion data via contrast-enhanced power Doppler ultrasound (median vascularity, median blood volume) provided additional information. Ninety-two samples were analyzed: sarcomas (n = 32), carcinomas (n = 30), and malignant melanomas (n = 30). Polarographic oxygen and perfusion data was available in 22.8% (sarcomas n = 9, carcinomas n = 7, melanomas n = 5), and 27.1% (sarcomas n = 10, carcinomas n = 8, melanomas n = 7) of cases, respectively. GLUT-1 expression was detected in 46.7% of all samples, and was generally weak. CAIX expression was found in 34.8% of all samples. Median Ki-67 score and MVD count was 19% and 17, respectively. The evaluation of the GLUT-1 score and continuous data showed significantly lower GLUT-1 levels in sarcomas (mean 5.1%, SD 6.2) versus carcinomas and melanomas (mean 16.5%/ 19.0%, SD 17.3/ 20.9, p = 0.001). The expression of CAIX correlated mildly positively with GLUT-1 (p = 0.018, rho = 0.250) as well as with Ki-67 (p = 0.014, rho = 0.295). MVD showed a significantly lower level in melanomas (mean 12.6, SD 7.7) versus sarcomas and carcinomas (mean 21.8/ 26.9, SD 13.0/20.4, p = 0.001). Median vascularity and blood volume were significantly lower in sarcomas (mean 10.4%, SD 11.0, and mean 6.3%, SD 6.5, respectively) versus carcinomas (mean 39.2%, SD 16.4 and mean 33.0%, SD 25.6, respectively) and melanomas (mean 36.0%, SD 18.3, and 31.5%, SD 24.5). Between the 3 histological groups, there was neither a significant difference in the GLUT-1 and CAIX score and continuous data, nor the Ki67 score, or polarographic oxygen measurements. GLUT-1 continuous data and Ki-67 (p<0.001, rho = 0.403), as well as Ki-67 and MVD (p = 0.029, rho = 0.228) correlated positively and a mild correlation was found between vascularity and GLUT-1 (p = 0.043, rho = 0.408). GLUT-1, CAIX, proliferative index and MVD levels were established as microenvironmental descriptors with the purpose of creating a baseline in order to follow changes seen in the tumor microenvironment after hypofractionated radiation with high doses. PMID- 26906572 TI - Expressing oceanic turbulence parameters by atmospheric turbulence structure constant. AB - The parameters composing oceanic turbulence are the wavelength, link length, rate of dissipation of kinetic energy per unit mass of fluid, rate of dissipation of mean-squared temperature, Kolmogorov microscale, and the ratio of temperature to salinity contributions to the refractive index spectrum. The required physical entities such as the average intensity and the scintillation index in the oceanic medium are formulated by using the power spectrum of oceanic turbulence, which is described by oceanic turbulence parameters. On the other hand, there exists a rich archive of formulations and results for the above-mentioned physical entities in atmospheric turbulence, where the parameters describing the turbulence are the wavelength, the link length, and the structure constant. In this paper, by equating the spherical wave scintillation index solutions in the oceanic and atmospheric turbulences, we have expressed the oceanic turbulence parameters by an equivalent structure constant used in turbulent atmosphere. Such equivalent structure constant will help ease reaching solutions of similar entities in an oceanic turbulent medium by employing the corresponding existing solutions, which are valid in an atmospheric turbulent medium. PMID- 26906573 TI - Local radial basis function meshless scheme for vector radiative transfer in participating media with randomly oriented axisymmetric particles. AB - A local radial basis function meshless scheme (LRBFM) is developed to solve polarized radiative transfer in participating media containing randomly oriented axisymmetric particles in which radial basis functions augmented with polynomial basis are employed to construct the trial functions, and the vector radiative transfer equation based on the discrete-ordinates approach is discretized directly by collocation method. The LRBFM belongs to a class of truly meshless methods that do not need any mesh or any numerical integration scheme. Performances of the LRBFM are verified with analytical solutions and other numerical results reported earlier in the literature via five various test cases. The predicted angular distribution of brightness temperature and Stokes vector by the LRBFM agree very well with the benchmark. It is demonstrated that the LRBFM is accurate to solve vector radiative transfer in participating media with randomly oriented axisymmetric particles. PMID- 26906571 TI - Time-lapse scanning surface plasmon microscopy of living adherent cells with a radially polarized beam. AB - We report on a fibered high-resolution scanning surface plasmon microscope for long term imaging of living adherent cells. The coupling of a high numerical aperture objective lens and a fibered heterodyne interferometer enhances both the sensitivity and the long term stability of this microscope, allowing for time lapse recording over several days. The diffraction limit is reached with a radially polarized illumination beam. Adherence and motility of living C2C12 myoblast cells are followed for 50 h, revealing that the dynamics of these cells change after 10 h. This plasmon enhanced evanescent wave microscopy is particularly suited for investigating cell adhesion, since it can not only be performed without staining of the sample but it can also capture in real time the exchange of extracellular matrix elements between the substrate and the cells. PMID- 26906574 TI - Far-field head-media optical interaction in heat-assisted magnetic recording. AB - We have used a plane wave expansion method to theoretically study the far-field head-media optical interaction in heat-assisted magnetic recording. For the Advanced Storage Technology Consortium media stack specifically, we notice the outstanding sensitivity related to the interlayer's optical thickness for media reflection and the magnetic layer's light absorption. With 10 nm interlayer thickness change, the recording layer absorption can be changed by more than 25%. The 2D results are found to correlate well with the full 3D model and magnetic recording tests on a flyable disc with different interlayer thickness. PMID- 26906575 TI - Ion-beam polishing of fused silica substrates for imaging soft x-ray and extreme ultraviolet optics. AB - We have studied the surface treatment of polished fused silica by neutralized Ar ions with energy of 500-1500 eV and incidence angles of 0-90 degrees . We found the following regularities: for samples that passed the standard procedure of deep polishing (initial effective roughness sigma(eff)~0.5 nm), the effective roughness decreases to the ultrasmooth level (i.e., sigma(eff)~0.25 nm in the range of spatial frequencies q?[4.9*10(-2)-63] MUm(-1)). The effect begins to be noticeable at the material removal of 150 nm and reaches saturation at depths of removal greater than 1 MUm. For supersmooth samples (sigma(eff)<0.3 nm), the effective roughness keeps the initial level at material removal down to tens of micrometers. The optimal ion energy range is 800-1300 eV (maximum smoothing effect); at higher energy some surface roughness degradation is observed. All the smoothing effects are observed at the incidence angle range theta(in)=0-35 degrees . Increasing the ion energy above 1300 eV increases the etching rate by up to 4 MUm per hour (J(ion)=0.8 mA/cm2), which allows for deep aspherization of sized substrates. The technique allows for manufacturing the optical elements for extreme ultraviolet and soft x-ray wavelength ranges with a numerical aperture of up to 0.6. PMID- 26906576 TI - Study on the mechanism of a charge-coupled device detector irradiated by millisecond pulse laser under functional loss. AB - The damage mechanism of a CCD detector was studied by building an experimental system containing a millisecond pulse laser irradiating a CCD detector. The experimental results show that the damage on the CCD detector was mainly thermal damage, along with mechanical damage. A melting phenomenon was caused by the thermal damage, so that a crater was observed on the surface of the CCD detector. Caused by melting of the polysilicon electrodes and a temperature rise in the silicon dioxide, the shift register impedance values were sharply reduced. Most of the substrate clock signals were broken and disappeared due to melting of channels in the silicon substrate layer, which caused a functional loss for the CCD detector. The mechanical damage on the melting edge of the CCD detector created heave; the temperature gradient caused this damage. In this paper, the decrease in vertical shift register impedance values was consistent with previous test results. PMID- 26906577 TI - High-birefringence photonic crystal fiber polarization filter based on surface plasmon resonance. AB - In this paper, we designed a C2v-symmetry-structured photonic crystal fiber with triangular lattice and Au-filled air holes. The finite element method is used to analyze the dispersion and confinement loss characteristics of the core mode and the surface plasmon mode of the metal wire. In this work, we found that the positions of resonance peaks and the resonance strength of core mode and surface plasmon mode can be well adjusted by changing the pitch between the cladding air holes and the diameters of the air holes or metal wires around the core. By optimizing the parameters of the fiber structure, a polarization filter at the communication band is designed. At the wavelength of 1.31 MUm, which is located in the communication band, the fundamental mode in X pol can be filtered with the diameter of the metal wire d(m)=1.2 MUm. When d(m)=1.4 MUm, the fundamental mode in Y pol can be filtered at the wavelength of 1.55 MUm, which is also located in the communication band. Compared with the ordinary single-polarization and single-mode photonic crystal fiber, the fiber we proposed in this paper can selectively filter out the polarized light in one direction by adjusting the wire diameter. It is meaningful for the development of the polarization filter in the communication band. PMID- 26906578 TI - Speckle reduction in laser projection displays through angle and wavelength diversity. AB - Speckle is the main obstacle for the use of laser light sources in projection technology. This paper focuses on speckle suppression by the reduction of temporal coherence which is provided by the broadband laser light. The investigation of the effect of laser spectrum width and multiple lasers on speckle contrast is discussed. A broader spectrum width of the laser light is attained by the use of multiple semiconductor laser diodes of the broad area type. Measurements of speckle contrast with and without angle diversity are performed for two and four laser diodes. The measurement of speckle contrast for a single laser diode is also presented for comparison. The experimental results show that multiple laser diodes provide lower speckle contrast as compared to a single laser diode. In addition, it is also shown in this paper that the wavelength distribution of independent laser diodes has an effect on speckle contrast. Two different types of blue laser diodes, Nichia NUB802T and Nichia NUB801E, which have slightly different central wavelengths, were used for the measurements. Four laser diodes with a combination of two types of laser diodes offer better speckle contrast reduction than four laser diodes of the same type due to an effective broader spectrum. Additional speckle contrast reduction is achieved through the angle diversity by using a dynamic deformable mirror. PMID- 26906579 TI - Tuning of a high magnification compact parabolic telescope for centimeter-scale laser beams. AB - Off-axis parabolic telescopes, widely used in astronomy and laser optics, if perfectly tuned, are virtually free from aberrations along the parabola's axis direction, but their alignment is very critical. We present a detailed method to align a high magnification off-axis afocal parabolic telescope. The method is composed of two steps: an initial pre-alignment using autocollimators, followed by a fine tuning with a collimated laser beam. Due to the large telescope magnification, the outcoming beam cannot be measured without being refocused. The beam is therefore reflected on a flat mirror and sent back through the telescope. This double-pass configuration allows the measurement of the beam quality without the need for large additional optics. In the fine-tuning step, a numerical simulation is also used to identify the degrees of freedom to be adjusted. The experimental results presented are obtained with one of the mode-matching parabolic telescopes of the gravitational wave interferometric detector Advanced Virgo. PMID- 26906580 TI - Two-dimensional trilayer grating with a metal/insulator/metal structure as a thermophotovoltaic emitter. AB - A thermophotovoltaic system that converts thermal energy into electricity has considerable potential for applications in energy utilization fields. However, intensive emission in a wide spectral and angular range remains a challenge in improving system efficiency. This study proposes the use of a 2D trilayer grating with a tungsten/silica/tungsten (W/SiO2/W) structure on a tungsten substrate as a thermophotovoltaic emitter. The finite-difference time-domain method is employed to simulate the radiative properties of the proposed structure. A broadband high emittance with an average spectral emittance of 0.953 between 600 and 1800 nm can be obtained for both transverse magnetic and transverse electric polarized waves. On the basis of the inductance-capacitance circuit model and dispersion relation analyses, this phenomenon is mainly considered as the combined contribution of surface plasmon polaritons and magnetic polaritons. A parametric study is also conducted on the emittance spectrum of the proposed structure, considering geometric parameters, polar angles, and azimuthal angles for both TM and TE waves. The study demonstrates that the emitter has good wavelength selectivity and polarization insensitivity in a wide geometric and angular range. PMID- 26906581 TI - Passive multispectral imaging polarimeter for remote atmospheric and surface studies: design based on optical coatings. AB - The passive imaging polarimeter architecture is based on optical coatings and thereby avoids the complexities of current systems that use rotating polarizers, phase-modulating retarders, and birefringent elements. Coatings on stationary elements separate spectral regions and their polarized components to simultaneously produce images of the Stokes linear polarization intensities in fields of view (FOVs) >=30 degrees . Wavelength and FOV coverages are limited only by the telescope and relay optics employed. The images are collected in identical spectral passbands that can extend from UV to shortwave IR. An example relevant to remote sensing in the 360-900 nm range is given. An on-board calibration and stability monitor is included. PMID- 26906582 TI - Ghost reflections of Gaussian beams in anamorphic optical systems with an application to Michelson interferometer. AB - In this paper, a methodology is developed to model and analyze the effect of undesired (ghost) reflections of Gaussian beams that are produced by anamorphic optical systems. The superposition of these beams with the nominal beam modulates the nominal power distribution at the recording plane. This modulation may cause contrast reduction, veiling parts of the nominal image, and/or the formation of spurious interference fringes. The developed methodology is based on synthesizing the beam optical paths into nominal and ghost optical beam paths. Similar to the nominal beam, we present the concept that each ghost beam is characterized by a beam size, wavefront radius of curvature, and Gouy phase in the paraxial regime. The nominal and ghost beams are sequentially traced through the system and formulas for estimating the electric field magnitude and phase of each ghost beam at the recording plane are presented. The effective electric field is the addition of the individual nominal and ghost electric fields. Formulas for estimating Gouy phase, the shape of the interference fringes, and the central interference order are introduced. As an application, the theory of the formation of the interference fringes by Michelson interferometer is presented. This theory takes into consideration the ghost reflections that are formed by the beam splitter. To illustrate the theory and to show its wide applicability, simulation examples that include a Mangin mirror, a Michelson interferometer, and a black box optical system are provided. PMID- 26906583 TI - 1 kHz 3.3 MUm Nd:YAG KTiOAsO4 optical parametric oscillator system for laser ultrasound excitation of carbon-fiber-reinforced plastics. AB - We present a new laser prototype for laser ultrasonics excitation. The fundamental wavelength of a Q-switched Nd:YAG laser with a repetition rate of 1 kHz is converted to 3.3 MUm with a KTiOAsO4 optical parametric oscillator. The achieved pulse energy at 3.3 MUm is 1.7 mJ, and the pulse duration at the fundamental wavelength of 1.06 MUm has been measured to be 21 ns. The ultrasonic excitation efficiency is about 3.5 times better compared to the application of state-of-the-art CO2 lasers. PMID- 26906584 TI - Robust method to improve the quality of shearographic phase maps obtained in harsh environments. AB - This paper presents a new approach to improve the quality of shearographic phase maps acquired in a harsh environment. During in-field nondestructive inspections, the presence of higher disturbances, mainly vibrations, can introduce unknown phase deviations in the sequence of shearographic images. This paper presents a different approach that combines the N-dimensional Lissajous algorithm [Int. J. Optomechatron.8, 340 (2014)1559-961210.1080/15599612.2014.942933] and the concept of phase of differences [Proc. SPIE6345, 634510 (2006)PSISDG0277 786X10.1117/12.693149] to improve the quality of phase maps. The concept is compared with two other methods. Results, advantages, and difficulties of each method are also presented and discussed by using real fringe maps. PMID- 26906585 TI - Random sub-Nyquist polarimetric modulator. AB - We show that it is possible to measure polarization with a polarimeter that gets rid of the seeing while still measuring at a frequency well below that of the seeing. We study a standard polarimeter made of two retarders and a beam splitter. The retarders are modulated at ~500 Hz, a frequency comparable to that of the variations of the refraction index in the earth's atmosphere, which is usually termed as seeing in astronomical observations. However, we assume that the camera is slow so that our measurements are time integrations of these modulated signals. In order to recover the time variation of the seeing and obtain the Stokes parameters we use the theory of compressed sensing to solve the demodulation by imposing a sparsity constraint on the Fourier coefficients of the seeing. We demonstrate the feasibility of this sub-Nyquist polarimeter using numerical simulations, both in the case without noise and with noise. We show that a sensible modulation scheme is obtained by randomly changing the fast axis of the modulators or their retardances in specific ways. We finally demonstrate that the value of the Stokes parameters can be recovered with great precision at almost maximum efficiency although it slightly degrades when the signal-to-noise ratio of the observations increases, a consequence of the multiplexing under the presence of photon noise. PMID- 26906586 TI - Capacity of electromagnetic communication modes in a noise-limited optical system. AB - We present capacity bounds of an optical system that communicates using electromagnetic waves between a transmitter and a receiver. The bounds are investigated in conjunction with a rigorous theory of degrees of freedom (DOF) in the presence of noise. By taking into account the different signal-to-noise ratio (SNR) levels, an optimal number of DOF that provides the maximum capacity is defined. We find that for moderate noise levels, the DOF estimate of the number of active modes is approximately equal to the optimum number of channels obtained by a more rigorous water-filling procedure. On the other hand, for very low- or high-SNR regions, the maximum capacity can be obtained using less or more channels compared to the number of communicating modes given by the DOF theory. In general, the capacity is shown to increase with increasing size of the transmitting and receiving volumes, whereas it decreases with an increase in the separation between volumes. Under the practical channel constraints of noise and finite available power, the capacity upper bound can be estimated by the well known iterative water-filling solution to determine the optimal power allocation into the subchannels corresponding to the set of singular values when channel state information is known at the transmitter. PMID- 26906587 TI - Polarization property analysis of a periscopic scanner with three-dimensional polarization ray-tracing calculus. AB - The polarization properties of a two-axis periscopic optical scanner constituted by a pair of rotating planar mirrors have been studied by using the three dimensional polarization ray-tracing matrix method. The separate and cumulative matrices that define the transformation of the polarization state are obtained and expressed in terms of the rotation angles of two mirrors. The variations of diattenuation and retardance are investigated and graphically shown as functions of the rotation angles. On this basis, a further investigation about the cumulative polarization aberrations of three different metal-coated periscopic scanners is accomplished. Finally, the output polarization states of the three metal-coated scanners are calculated with the input beam of the arbitrary polarization states, and the results show that aluminum film is more appropriate than gold film or silver film for the polarization-maintaining periscopic scanner. PMID- 26906588 TI - Boiling effect in liquid nitrogen directly cooled Yb3+:YAG laser. AB - Liquid nitrogen (LN2) behavior on the surface of excited Yb(3+):YAG is investigated using fluorometry. From the time-resolved temperature variations and integrated fluorescence spectra intensity on this directly cooled Yb(3+):YAG surface, we observe a phase transition of LN2 from nucleate boiling to film boiling. As a result of this pool boiling, good beam quality should occur when the temperature and heat flux at an excited surface of Yb(3+):YAG are below 95 K and 15.8 W/cm2, respectively. That is, the LN2 should remain in a steady state of nucleate boiling to produce good beam quality using pool boiling. PMID- 26906589 TI - High-output LED-based light engine for profile lighting fixtures with high color uniformity using freeform reflectors. AB - In the stage lighting and entertainment market, light engines (LEs) for lighting fixtures are often based on high-intensity discharge (HID) bulbs. Switching to LED-based light engines gives possibilities for fast switching, additive color mixing, a longer lifetime, and potentially, more energy-efficient systems. The lumen output of a single LED is still not sufficient to replace an HID source in high-output profile fixtures, but combining multiple LEDs can create an LE with a similar output, but with added complexity. This paper presents the results of modeling and testing such a light engine. Custom ray-tracing software was used to design a high-output red, green and blue LED-based light engine with twelve CBT 90 LEDs using a dual-reflector principle. The simulated optical system efficiency was 0.626 with a perfect (R=1) reflector coating for light delivered on a target surface through the entire optical system. A profile lighting fixture prototype was created, and provided an output of 6744 lumen and an efficiency of 0.412. The lower efficiency was mainly due to a non-optimal reflector coating, and the optimized design is expected to reach a significantly higher efficiency. PMID- 26906590 TI - Investigation of a field-widened Mach-Zehnder receiver to extend Fe Doppler lidar wind measurements from the thermosphere to the ground. AB - A receiver employing a field-widened Mach-Zehnder interferometer (MZI) is investigated for extending the wind measurement range of a narrow-band Fe Doppler lidar operating at 372 nm from its existing measurement range in the mesosphere and lower thermosphere (MLT) down to near the ground. This design uses the multiple transmitted frequencies available from the base Fe Doppler lidar in combination with a novel MZI receiver to make a measurement of the Doppler shift that rejects the influence of atmospheric parameters such as the aerosol backscatter ratio, temperature, and pressure of the lidar volume and receiver parameters such as the geometric overlap, the chopper function, and any other factor affecting the proportion of the signal in both channels of the MZI equally. A ratio is constructed from the three frequencies and two channels of the interferometer that exhibits a measurement performance of 1.75 times the Cramer-Rao lower bound, which is comparable to the dual MZI (DMZ) while preserving the insensitivity to backscatter spectrum of the quad MZI (QMZ). In addition, we show how the use of multiple transmitted frequencies can yield a wind measurement wherein the accuracy is insensitive to the optical imperfection and misalignment of the MZI or any other factor that affects the contrast, though the precision is still impacted by the fringe contrast. Simply adding a second surface mirror of a particular thickness to the basic tilted MZI can allow the field of the MZI to be widened sufficiently for most resonance Doppler lidar receivers in operation today. Provided that the detection sensitivity in each channel is known, the original resonance fluorescence and Rayleigh scattering signals can be recovered by simply scaling and adding the contributions from both channels. Consequently, the wind and temperature from the MLT region and the temperature from the Rayleigh region can be derived alongside the Rayleigh Doppler wind measurement without compromising the measurement precision. Using actual data obtained recently from a Major Research Instrumentation Fe Doppler lidar, we show the expected measurement performance and some potential scientific avenues for this embodiment of a "whole-atmosphere" lidar system. PMID- 26906591 TI - Multi-class remote sensing object recognition based on discriminative sparse representation. AB - The automatic recognition of multi-class objects with various backgrounds is a big challenge in the field of remote sensing (RS) image analysis. In this paper, we propose a novel recognition framework for multi-class RS objects based on the discriminative sparse representation. In this framework, the recognition problem is implemented in two stages. In the first, or discriminative dictionary learning stage, considering the characterization of remote sensing objects, the scale invariant feature transform descriptor is first combined with an improved bag-of words model for multi-class objects feature extraction and representation. Then, information about each class of training samples is fused into the dictionary learning process; by using the K-singular value decomposition algorithm, a discriminative dictionary can be learned for sparse coding. In the second, or recognition, stage, to improve the computational efficiency, the phase spectrum of a quaternion Fourier transform model is applied to the test image to predict a small set of object candidate locations. Then, a multi-scale sliding window mechanism is utilized to scan the image over those candidate locations to obtain the object candidates (or objects of interest). Subsequently, the sparse coding coefficients of these candidates under the discriminative dictionary are mapped to the discriminative vectors that have a good ability to distinguish different classes of objects. Finally, multi-class object recognition can be accomplished by analyzing these vectors. The experimental results show that the proposed work outperforms a number of state-of-the-art methods for multi-class remote sensing object recognition. PMID- 26906592 TI - Ultracompact polarization rotator in an asymmetric single dielectric loaded rib waveguide. AB - A compact polarization rotator (PR) with an asymmetric single dielectric loaded rib waveguide is proposed. The core of the waveguide is designed to have a specific rectangular configuration. The waveguide requires only a single asymmetrical dielectric loading on the core to complete the polarization conversion. The optical field is confined to the vicinity of the core center, which matches the optical field of the input/output waveguides. The transition loss of the PR is as low as 0.03-0.21 dB/facet without the taper or offset schemes. Such results can facilitate the fabrication of a PR with an operating length of 10 MUm. In a comprehensively designed PR with a length of 7.92 MUm, a 1 dB bandwidth for polarization conversion efficiency (PCE) is greater than 100 nm at the communicating wavelength of 1550 nm. The loading width and thickness with +/-20 nm tolerance exhibit -0.87 and -0.49 dB changes in PCE, respectively. PMID- 26906593 TI - Multiple-input multiple-output synthetic aperture ladar system for wide-range swath with high azimuth resolution. AB - For the trade-off between the high azimuth resolution and the wide-range swath in the single-input single-output synthetic aperture ladar (SAL) system, the range swath of the SAL system is restricted to a narrow range, this paper proposes a multiple-input multiple-output (MIMO) synthetic aperture ladar system. The MIMO system adopts a low pulse repetition frequency (PRF) to avoid a range ambiguity for the wide-range swath and in azimuth adopts the multi-channel method to achieve azimuth high resolution from the unambiguous azimuth wide-spectrum signal, processed through adaptive digital beam-forming technology. Simulations and analytical results are presented. PMID- 26906594 TI - Measuring vibrational motion in the presence of speckle using off-axis holography. AB - We present a holographic laser vibrometer designed to mitigate the effects of speckle noise when measuring the vibrational motion of a rough object. We show that multiplexing the interferometric measurement across 105 pixels provides a 50 dB reduction in the incoherent noise. Using a high-speed camera, this enables a displacement sensitivity of 50 fm/?Hz with a bandwidth of 12.5 kHz when measuring rough objects, representing a 20 dB improvement compared with a commercially available single-detector-based laser vibrometer. Finally, we show that the holographic vibrometer system is capable of stand-off acoustic sensing by measuring the acoustic-induced vibrations of a piece of paper with sensitivity as low as 10 dB (re 20 MUPa). The ability to sensitively and noninvasively measure the vibrations of arbitrary rough surfaces could enable new applications in laser vibrometry. PMID- 26906595 TI - Inverse problem of determining periodic surface profile oscillation defects of steel materials with a fiber Bragg grating sensor. AB - We propose and experimentally demonstrate a method for the detection of steel material defects utilizing a fiber Bragg grating sensor. The considered defects are periodic grooves along the length of the tested steel profile. Direct measurement of the spectral reflectance characteristics of the fiber is performed, and the related inverse problem of indirect defect shape determination is solved. It has been demonstrated that the defect periodicity estimation is 2.5 mm, with an error of less than 0.1. Furthermore, it has been shown that for periodic intervals of the order of 5 mm, the difference between the strain amplitude calculated using our method and the amplitude obtained via the finite element method was 1.4 mepsilon. PMID- 26906596 TI - Efficient reconstruction method for ground layer adaptive optics with mixed natural and laser guide stars. AB - The imaging quality of modern ground-based telescopes such as the planned European Extremely Large Telescope is affected by atmospheric turbulence. In consequence, they heavily depend on stable and high-performance adaptive optics (AO) systems. Using measurements of incoming light from guide stars, an AO system compensates for the effects of turbulence by adjusting so-called deformable mirror(s) (DMs) in real time. In this paper, we introduce a novel reconstruction method for ground layer adaptive optics. In the literature, a common approach to this problem is to use Bayesian inference in order to model the specific noise structure appearing due to spot elongation. This approach leads to large coupled systems with high computational effort. Recently, fast solvers of linear order, i.e., with computational complexity O(n), where n is the number of DM actuators, have emerged. However, the quality of such methods typically degrades in low flux conditions. Our key contribution is to achieve the high quality of the standard Bayesian approach while at the same time maintaining the linear order speed of the recent solvers. Our method is based on performing a separate preprocessing step before applying the cumulative reconstructor (CuReD). The efficiency and performance of the new reconstructor are demonstrated using the OCTOPUS, the official end-to-end simulation environment of the ESO for extremely large telescopes. For more specific simulations we also use the MOST toolbox. PMID- 26906597 TI - Helical long-period grating formed in a thinned fiber and its application to a refractometric sensor. AB - A new kind of helical long-period grating (HLPG) written by using a CO2 laser is proposed and experimentally demonstrated, in which a sapphire tube (to be used as a miniature oven with a constant temperature inside) is specially utilized in place of the commonly used ZnSe focused-lens. The proposed method allows fabrication of a HLPG in a thinned fiber with a diameter smaller than several tens of micrometers. As an application of this kind of HLPG, a unique fiber sensor that allows for temperature-insensitive measurement of the refractive index is proposed and experimentally demonstrated, which is based on utilization of two cascaded HLPGs but with different transverse diameters. PMID- 26906598 TI - Generalized design of a zero-geometric-loss, astigmatism-free, modified four objective multipass matrix system. AB - During this study we constructed a generalized parametric modified four-objective multipass matrix system (MMS). We used an optical system comprising four asymmetrical spherical mirrors to improve the alignment process. The use of a paraxial equation for the design of the front transfer optics yielded the initial condition for modeling our MMS. We performed a ray tracing simulation to calculate the significant aberration of the system (astigmatism). Based on the calculated meridional and sagittal focus positions, the complementary focusing mirror was easily designed to provide an output beam free of astigmatism. We have presented an example of a 108-transit multipass system (5*7 matrix arrangement) with a relatively larger numerical aperture source (xenon light source). The whole system exhibits zero theoretical geometrical loss when simulated with Zemax software. The MMS construction strategy described in this study provides an anastigmatic output beam and the generalized approach to design a controllable matrix spot pattern on the field mirrors. Asymmetrical reflective mirrors aid in aligning the whole system with high efficiency. With the generalized design strategy in terms of optics configuration and asymmetrical fabrication method in this paper, other kinds of multipass matrix system coupled with different sources and detector systems also can be achieved. PMID- 26906599 TI - Photon-conversion and sensitization evaluation of Eu3+ in a borate glass system. AB - Photon conversion is exhibited in a borate (LKZBSB) glass system containing Eu(3+), and the enhanced characteristic emissions of Eu(3+) with the codoping of Ce(3+) have been verified. A large Judd-Ofelt intensity parameter Omega2 of Eu(3+) indicates a high asymmetrical and strong covalent environment around rare earth (RE) ions in LKZBSB glasses and spontaneous emission probability and a maximum emission cross section of the dominant 5D0->7F2 transition were derived to be 370 s(-1) and 1.28*10(-21) cm2, respectively, revealing the potential UV >visible photon-conversion capacity of Eu(3+). Absolutely quantitative evaluation illustrates that Eu(3+) is a favorable photon-conversion center to achieve high photon-conversion efficiency. The addition of Ce(3+) is beneficial to realizing effective red emission of Eu(3+), which possesses commercial value by decreasing the dopant of expensive europium compounds. As an expectation, this photon conversion LKZBSB glass system can promote the development of a photon downconversion layer for solar cells, which are particularly used in outer space with intense UV radiation. PMID- 26906600 TI - Simultaneous imaging of fuel vapor mass fraction and gas-phase temperature inside gasoline sprays using two-line excitation tracer planar laser-induced fluorescence. AB - This paper reports for the first time, to the best of our knowledge, on the simultaneous imaging of the gas-phase temperature and fuel vapor mass fraction distribution in a direct-injection spark-ignition (DISI) spray under engine relevant conditions using tracer planar laser-induced fluorescence (TPLIF). For measurements in the spray, the fluorescence tracer 3-pentanone is added to the nonfluorescent surrogate fuel iso-octane, which is excited quasi-simultaneously by two different excimer lasers for two-line excitation LIF. The gas-phase temperature of the mixture of fuel vapor and surrounding gas and the fuel vapor mass fraction can be calculated from the two LIF signals. The measurements are conducted in a high-temperature, high-pressure injection chamber. The fluorescence calibration of the tracer was executed in a flow cell and extended significantly compared to the existing database. A detailed error analysis for both calibration and measurement is provided. Simultaneous single-shot gas-phase temperature and fuel vapor mass fraction fields are processed for the assessment of cyclic spray fluctuations. PMID- 26906601 TI - Generalized phase-shifting algorithms: error analysis and minimization of noise propagation. AB - Phase shifting is a technique for phase retrieval that requires a series of intensity measurements with certain phase steps. The purpose of the present work is threefold: first we present a new method for generating general phase-shifting algorithms with arbitrarily spaced phase steps. Second, we study the conditions for which the phase-retrieval error due to phase-shift miscalibration can be minimized. Third, we study the phase extraction from interferograms with additive random noise, and deduce the conditions to be satisfied for minimizing the phase retrieval error. Algorithms with unevenly spaced phase steps are discussed under linear phase-shift errors and additive Gaussian noise, and simulations are presented. PMID- 26906602 TI - Highly sensitive surface plasmon resonance sensor utilizing a long period grating with photosensitive cladding. AB - In this study, we propose and investigate a novel grating-assisted surface plasmon resonance (SPR) platform based on a silver coated long period fiber grating having a photosensitive cladding (C-LPFG). We show that the SPR mode is transited from the higher EH mode with an effective refractive index (ERI) close to that of the surrounding refractive index (SRI) and is highly sensitive to a change in the SRI. Compared with a conventional SPR sensor, a much higher sensitivity is obtained for the novel C-LPFG-based SPR sensor. The sensitivity can be further improved by reducing the fiber diameter. The numerical results show that the highest local sensitivity, which can be as high as ~4900 nm/RIU, and the corresponding resolution of ~2.04*10(-6) RIU are achieved for the reduced silver coated C-LPFG sensor. Moreover, the Q-factor and the figure of merit exhibit better characteristics than those of the conventional LPFG-based SPR sensor. Our findings provide insight into the C-LPFG-based SPR platform being a potentially important area to explore for biochemical sensing. PMID- 26906603 TI - Magnetorheological finishing of chemical-vapor deposited zinc sulfide via chemically and mechanically modified fluids. AB - We describe the anisotropy in the material removal rate (MRR) of the polycrystalline, chemical-vapor deposited zinc sulfide (ZnS). We define the polycrystalline anisotropy via microhardness and chemical erosion tests for four crystallographic orientations of ZnS: (100), (110), (111), and (311). Anisotropy in the MRR was studied under magnetorheological finishing (MRF) conditions. Three chemically and mechanically modified magnetorheological (MR) fluids at pH values of 4, 5, and 6 were used to test the MRR variations among the four single-crystal planes. When polishing the single-crystal planes and the polycrystalline with pH 5 and pH 6 MR fluids, variations were found in the MRR among the four single crystal planes and surface artifacts were observed on the polycrystalline material. When polishing the single-crystal planes and the polycrystalline with the modified MR fluid at pH 4, however, minimal variation was observed in the MRR among the four orientations and a reduction in surface artifacts was achieved on the polycrystalline material. PMID- 26906604 TI - Calculation of the radiation forces on a microsphere in the evanescent field of an optical nanofiber by ray tracing. AB - We use ray optics to calculate the radiation forces on a dielectric microsphere in the evanescent field of an optical nanofiber. We theoretically demonstrate that the gradient force may attract the microsphere onto the fiber surface. The scattering force may transport the microsphere along the fiber and in the light propagating direction. The impact of the sphere-fiber distance, sphere radius, and fiber radius on the scattering and gradient forces are investigated. The radius of nanofiber can be optimized for particle transportation. PMID- 26906605 TI - Fast optimization method based on the diffuser dot density for uniformity of the backlight module. AB - A fast optimization method based on the diffuser dot density (DDD) for uniformity of the backlight module (BLM) is proposed in the paper. First, the relationship between the efficiency of the light emerging and the DDD is analyzed, and then a simulation model that is employed to acquire a serial of simulating data is constructed. Second, a mathematic method to profit the relationship is adopted, and a polynomial relationship is derived. Finally, an algorithm to adjust the DDD and optimize the uniformity of the BLM based on the DDD is constructed. The simulation results prove that only by three times optimization, the uniformity of the BLM can reach 85.6%, and the experimental result indicates that the algorithm proposed in the paper can improve the uniformity rapidly. The final experimental result is that the uniformity of the third optimization reaches 77.4%, which satisfies the target 75% in the phase of designing the BLM. Compared to the conventional optimization method, the method can speed up the procedure and lower the expense of developing the BLM in fabricating the liquid-crystal display. PMID- 26906606 TI - Encoded error calibration for a coded aperture spectrometer based on deconvolution. AB - The principle of a 2D coded aperture spectrometer is described in this paper. The crosstalk of adjacent rows, which is caused by the optical system's point-spread function and the nonuniform illumination of the apertures, is the main source of the system decoded errors. Through the analysis of the effect of the crosstalk and nonuniform illumination on the decoded spectrum, the encoding matrix is modified. Based on the new encoding equation, an algorithm using Gold's deconvolution method is proposed to remove the crosstalk of adjacent rows. In the end, we evaluate the effect of this method through a series of contrast experiments. PMID- 26906607 TI - [Association between IGF system and PAPP-A in coronary atherosclerosis]. AB - Atherosclerosis is a condition that involves multiple pathophysiological mechanisms and whose knowledge has not been fully elucidated. Often, scientific advances on the atherogenic pathophysiology generate that molecules not previously considered in the scene of this disease, were attributed actions on the onset or progression of it. A representative example is the study of a new mechanism involved in the atherogenic process, consisting of the association between the insulin-like growth factor (IGF) system and pregnancy-associated plasma protein-A (PAPP-A). Insulin-like growth factor system is a family of peptides that include 3 peptide hormones, 4 transmembrane receptors and 6 binding proteins. Insulin-like growth factor-1 (IGF-1) is the main ligand of the IGF system involved in coronary atherosclerosis. IGF-1 exerts its effects via activation of the IGF-1R receptor on vascular smooth muscle cells or macrophages. In vascular smooth muscle cells promotes migration and prevents apoptosis which increases plaque stability while in macrophages reduces reverse cholesterol transport leading to the formation of foam cells. Regulation of IGF-1 endothelial bioavailability is carried out by IGFBP proteases, mainly by PAPP-A. In this review, we address the mechanisms between IGF system and PAPP-A in atherosclerosis with emphasis on molecular effects on vascular smooth muscle cells and macrophages. PMID- 26906608 TI - Early Nutrition and Its Effects on Growth, Body Composition and Later Obesity. PMID- 26906609 TI - A theoretical study on the reaction of ozone with aqueous iodide. AB - Atmospheric iodine chemistry plays a key role in tropospheric ozone catalytic destruction, new particle formation, and as one of the possible sinks of gaseous polar elemental mercury. Moreover, it has been recently proposed that reaction of ozone with iodide on the sea surface could be the major contributor to the chemical loss of atmospheric ozone. However, the mechanism of the reaction between aqueous iodide and ozone is not well known. The aim of this paper is to improve the understanding of such a mechanism. In this paper, an ab initio study of the reaction of aqueous iodide and ozone is presented, evaluating thermodynamic data of the different reactions proposed in previous experimental studies. In addition, the structures, energetics and possible evolution of the key IOOO(-) intermediate are discussed for the first time. PMID- 26906610 TI - New Momentum for the Field of Oligonucleotide Therapeutics. PMID- 26906613 TI - Genotoxicity in Mice Following AAV Gene Delivery: A Safety Concern for Human Gene Therapy? PMID- 26906614 TI - The BCG Strain Pool: Diversity Matters. PMID- 26906615 TI - Under Pressure: Elevated Blood Pressure Enhances Targeting of Tumors by Oncolytic Viruses. PMID- 26906617 TI - Synthesis and characterization of bridged bis(amidato) rare earth metal amides and their applications in C-N bond formation reactions. AB - Based on three bisamide proligands H2Ln (n = 1-3) (H2L1 = [(Me3C6H2CONHCH2)2CH2], H2L2 = [(Me3C6H2CONHCH2)2C(CH3)2], H2L3 = [Me3C6H2CONH(CH2)2]2NCH3), eight bis(amidato) trivalent rare-earth metal amides {LnRE[N(TMS)2]}2 (n = 1, RE = La (1), Sm (2), Nd (3), Y (4); n = 2, RE = La (5), Nd (6);n = 3, RE = La (7), Nd (8); TMS = SiMe3) were successfully synthesized by treatment of H2Ln with RE[N(TMS)2]3 in a 1 : 1 molar ratio. Complexes 3, and 5-8 were characterized by single-crystal X-ray diffraction, and NMR characterization was carried out for the La complexes 1, 5, 7 and the Y complex 4. These complexes exhibited high catalytic activities in both the direct amidation of aldehydes and the addition of amines with carbodiimine. It was found that the bis(amidato) rare earth metal amides bearing different linkers have different effects on the transformations and lanthanum and neodymium complexes performed better than others. PMID- 26906618 TI - Proceedings of the WSCTS 25th Anniversary Congress. PMID- 26906616 TI - Association between Serum Polybrominated Diphenyl Ether Levels and Residential Proximity to Solid-Waste Facilities. AB - As consumer products treated with polybrominated diphenyl ethers (PBDEs) reach the end of their life cycle, they often are discarded into solid-waste facilities, offering a potential reservoir for exposure. The likelihood of exposures to PBDEs by residents living near those sites rarely has been explored. This study collected blood samples from 923 female participants in the California Teachers Study in 2011-2013 and examined the association between participants' residential proximity to solid-waste facilities with potential release of PBDEs and serum levels of three congeners (BDE-47, BDE-100, and BDE-153). General linear regression analysis was used to examine the association, adjusting for age, race, body-mass index, neighborhood socioeconomic status, and urban residency. Compared to participants living >10 km from any selected site, those living within 2 km had 45% higher BDE-47 (95% CI: 5-100%) and BDE-100 (95% CI: 0 109%) levels, and those living between 2 and 10 km had 35% higher BDE-47 (95% CI: 0-82%) and 29% higher BDE-100 (95% CI: -9 to 82%) levels. No associations were found for BDE-153. Living close to some solid waste sites may be related to higher serum BDE-47 and BDE-100 levels. Studies with comprehensive exposure assessments are needed to confirm these initial observations. PMID- 26906619 TI - Differential Regulation of SOX9 Protein During Chondrogenesis of Induced Pluripotent Stem Cells Versus Mesenchymal Stromal Cells: A Shortcoming for Cartilage Formation. AB - Induced pluripotent stem cells (iPSCs) are an attractive cell source for cartilage regeneration, but current in vitro chondrogenic differentiation protocols yield insufficient results. In search for shortcomings of iPSC chondrogenesis, this study investigated whether SOX9 protein was adequately regulated during multiphase chondrogenic differentiation of two human iPSC lines in a comparable manner like during mesenchymal stromal cell (MSC) chondrogenesis. Upon generation of intermediate mesenchymal progenitor cells (iMPCs), SOX9 was induced and reached variable protein levels compared to MSCs. Along with an altered condensation behavior, iMPC cartilage formation was less robust compared to MSCs and better in the iMPC line with higher SOX9 protein levels. Despite efficient Smad-2/3 phosphorylation, TGF-beta-driven chondrogenic stimulation downregulated SOX9 protein in iMPCs rather than increasing levels like in MSCs. Chondrogenesis was further improved by cotreatment with TGF-beta + BMP-4, which appeared to shorten the duration of the SOX9 protein decline. However, this was insufficient to overcome heterogenic outcome and came at the expense of undesired hypertrophy. In iMPCs, but not MSCs, high levels of the SOX9-antagonizing hsa-miR 145 correlated with low SOX9 protein quantity. Thus, considerable iMPC heterogeneity with variable SOX9 protein levels, an altered condensation pattern, and low early SOX9 inducibility appeared as critical shortcomings of iPSC chondrogenesis. We suggest consistent quality of intermediate cell populations with high SOX9 protein induction as important indicators to obtain robust cartilage formation from iPSCs. The impact of this study is the identification of a SOX9 protein regulation opposite to MSC chondrogenesis that will now enable a selective adaptation of the currently limited protocols to the specific needs of iPSCs. PMID- 26906620 TI - [Modeling a clinical process for differentiated thyroid cancer health care in Hospital Base Valdivia, Chile]. AB - OBJECTIVE: To design a clinical process model in the management of differentiated thyroid cancer in order to improve accessibility to this treatment. MATERIAL AND METHODS: Based on modified Participatory Action Research, a model design process was conducted using a literature review and meetings with organisations committed to the redesigning process, and to agree an improved and feasible process. RESULTS: The process map was constructed by participatory action including, characterisation of the value chain, fault detection in the flow of the process, relevant documents and process for proposing modifications and approvals necessary for this purpose. Links were established between the main process and the support and strategic processes. The participatory model helped to cut the waiting times for diagnosis and treatment of this disease from 12 to 4 months. CONCLUSIONS: For each unit to be able to fully visualise the map of the process and understand their contribution as a set of integrated contributions and not fragmented, helps in the comprehensive management of patients and operation processes based on the hierarchical and dominant organisational model in Chilean hospitals. To analyse and remodel clinical processes by participatory action helps to limit failures in the fluidity of care of the patients, by presenting each participating unit with a general view of the process, the problems, and the possible solutions. Furthermore, this approach helps to clarify the process in order to make it more efficient, to harmonise relationships, and to improve coordination in order to optimise patient care. PMID- 26906621 TI - [Can anybody understand the informed consent documents? A proposal to make it easier]. AB - OBJECTIVE: To assess the readability of informed consent documents as written by doctors, by analysing the results and the differences between the sections of the document and services, with the aim of helping to improve them. MATERIAL AND METHODS: Descriptive study of the texts from 359 documents sent for accreditation in the Arrixaca Hospital (Murcia, Spain). Both length and readability are assessed. Length is measured in words (adequate up to 470, excessive over 940), and readability in INFLESZ points (suitable if over 55). RESULTS: Length ranged from 73 to 1018 words (mean 360, standard error 8.8, adequate length OR 3.66+/ 0.81). The larger sections were "risks" and "nature of the procedure", and the shorter ones, "alternatives" and "contraindications", P<.0001. The INFLESZ value ranged from 18.1 to 86.4 points (mean 45.8, standard error 0.45), and was better in non-surgical services. Only 12.5% of the documents achieved an INFLESZ value over 55 (OR 0.12+/-0.03), with 70% in non-surgical procedures, P<.0001. The better readability sections were the "nature" and the "risks", and the worst ones, were "contraindications" and "alternatives", P<.0001. CONCLUSIONS: The length of proposed documents is adequate, but they are not sufficiently readable, especially if they come from surgical services. The section length is unbalanced, with "contraindications" and "alternatives" being shorter and more difficult to understand. It is essential to check the readability before using an informed consent document. For this purpose, tools like that proposed could be useful. PMID- 26906622 TI - Essential role of STX6 in esophageal squamous cell carcinoma growth and migration. AB - Abnormalities in endosomes, or dysregulation in their trafficking, play an important role directly in many diseases including oncogenesis. Syntaxin-6 (STX6) is involved in diverse cellular functions in a variety of cell types and has been shown to regulate many intracellular membrane trafficking events such as endocytosis, recycling and anterograde and retrograde trafficking. However, its expression pattern and biological functions in esophageal squamous cell carcinoma (ESCC) remained unknown. Here, we have found that the expression of STX6 was up regulated in ESCC samples, its expression was significantly correlated with tumor size, histological differentiation, lymph node metastasis and depth. On one hand, STX6 silencing inhibited ESCC cells viability and proliferation in a p53 dependent manner. On the other hand, STX6 effect integrin trafficking and regulate ESCC cells migration. Taken together, our study revealed the oncogenic roles of STX6 in the progression of ESCC, and it might be a valuable target for ESCC therapy. PMID- 26906623 TI - MiR-590-5p-meidated LOX-1 upregulation promotes Angiotensin II-induced endothelial cell apoptosis. AB - BACKGROUND: Endothelial cell apoptosis contributes to cardiovascular diseases such as hypertension, atherosclerosis. MicroRNA regulates endothelial cell function but its role in endothelial cell apoptosis remains to be fully elucidated. This study aims to investigate the role of miR-590-5p in endothelial cell apoptosis and dissect the underlying mechanisms. METHODS: Flow cytometric analysis, Hoechst 33258 staining and Western blotting were performed to evaluate human umbilical vein endothelial cell (HUVEC) apoptosis induced by Angiotensin (Ang) II. Western blotting and real-time quantitative PCR were conducted to assess the expression of LOX-1. DCFH-DA staining was carried out to measure the generation of reactive oxygen species (ROS). RESULTS: Ang II-induced HUVEC apoptosis was accompanied by downregulation of miR-590-5p; administration of miR 590-5p mimics attenuated HUVEC apoptosis and decreased ROS generation, as indicated by reduced fraction of apoptotic HUVECs and decreased caspase-3 activity. LOX-1 expression was increased by Ang II, and miR-590-5p mimics reduced LOX-1 expression in HUVECs in the absence or presence of Ang II. Pharmacologic or genetic block of LOX-1 with small interference RNA or TS92 (LOX-1 neutralizing antibody) significantly ameliorated HUVEC apoptosis, as evidenced by reduced number of apoptotic HUVECs, inhibited caspase-3 activation and suppressed mitochondrial cytochrome C release. Moreover, LOX-1 siRNA or TS92 treatment dramatically reduced ROS production in HUVECs treated with Ang II. CONCLUSION: Our data demonstrated that miR-590-5p downregulation promoted Ang II-induced endothelial cell apoptosis by elevating LOX-1 expression and consequently increasing ROS generation. Thus, restoration of miR-590-5p or block of LOX-1 could be therapeutically exploited to alleviate endothelial cell apoptosis. PMID- 26906624 TI - Co-transforming bar and CsLEA enhanced tolerance to drought and salt stress in transgenic alfalfa (Medicago sativa L.). AB - Drought and high salinity are two major abiotic factors that restrict alfalfa productivity. A dehydrin protein, CsLEA, from the desert grass Cleistogenes songorica was transformed into alfalfa (Medicago sativa L.) via Agrobacterium mediated transformation using the bar gene as a selectable marker, and the drought and salt stress tolerances of the transgenic plants were assessed. Thirty nine of 119 transformants were positive, as screened by Basta, and further molecularly authenticated using PCR and RT-PCR. Phenotype observations revealed that the transgenic plants grew better than the wild-type (WT) plants after 15d of drought stress and 10d of salt stress: the leaves of WT alfalfa turned yellow, whereas the transgenic alfalfa leaves only wilted; after rewatering, the transgenic plants returned to a normal state, though the WT plants could not be restored. Evaluation of physiologic and biochemical indices during drought and salt stresses showed a relatively lower Na(+) content in the leaves of the transgenic plants, which would reduce toxic ion effects. In addition, the transgenic plants were able to maintain a higher relative water content (RWC), higher shoot biomass, fewer photosystem changes, decreased membrane injury, and a lower level of osmotic stress injury. These results demonstrate that overexpression of the CsLEA gene can enhance the drought and salt tolerance of transgenic alfalfa; in addition, carrying the bar gene in the genome may increase herbicide resistance. PMID- 26906625 TI - Determining layer number of two-dimensional flakes of transition-metal dichalcogenides by the Raman intensity from substrates. AB - Transition-metal dichalcogenide (TMD) semiconductors have been widely studied due to their distinctive electronic and optical properties. The property of TMD flakes is a function of their thickness, or layer number (N). How to determine the N of ultrathin TMD materials is of primary importance for fundamental study and practical applications. Raman mode intensity from substrates has been used to identify the N of intrinsic and defective multilayer graphenes up to N = 100. However, such analysis is not applicable to ultrathin TMD flakes due to the lack of a unified complex refractive index (n) from monolayer to bulk TMDs. Here, we discuss the N identification of TMD flakes on the SiO2/Si substrate by the intensity ratio between the Si peak from 100 nm (or 89 nm) SiO2/Si substrates underneath TMD flakes and that from bare SiO2/Si substrates. We assume the real part of n of TMD flakes as that of monolayer TMD and treat the imaginary part of n as a fitting parameter to fit the experimental intensity ratio. An empirical n, namely, n(eff), of ultrathin MoS2, WS2 and WSe2 flakes from monolayer to multilayer is obtained for typical laser excitations (2.54 eV, 2.34 eV or 2.09 eV). The fitted n(eff) of MoS2 has been used to identify the N of MoS2 flakes deposited on 302 nm SiO2/Si substrate, which agrees well with that determined from their shear and layer-breathing modes. This technique of measuring Raman intensity from the substrate can be extended to identify the N of ultrathin 2D flakes with N-dependent n. For application purposes, the intensity ratio excited by specific laser excitations has been provided for MoS2, WS2 and WSe2 flakes and multilayer graphene flakes deposited on Si substrates covered by a 80-110 nm or 280-310 nm SiO2 layer. PMID- 26906626 TI - Simultaneous synthesis/assembly of anisotropic cake-shaped porphyrin particles toward colloidal microcrystals. AB - The one-step synthesis/assembly of a cake-shaped porphyrin colloidal microcrystal with tailored height-diameter was demonstrated based on interfacial assembly and the water-droplet template. The as-fabricated anisotropic colloidal crystals showed special optic properties and enhanced optic-limiting behavior. PMID- 26906627 TI - Thrombocytopenia and subcutaneous bleedings in a patient with Zika virus infection. PMID- 26906628 TI - "Thyroid Steal"--A Historical Approach to Thyroid Surgery for Graves' Disease. PMID- 26906629 TI - Inequalities in the uptake of weight management interventions in a pragmatic trial: an observational study in primary care. AB - BACKGROUND: Primary care referral to a commercial open-group behavioural weight loss programme is a cost-effective intervention, but only 10% of patients receiving this intervention are male. AIM: To explore whether observed biases in participation in these interventions reflect biases in the uptake of the invitation to participate. DESIGN AND SETTING: Comparison of invited population and recruited participants in a multicentre randomised controlled trial of primary care referral to a commercial open-group behavioural weight-loss programme in England (WRAP [Weight loss Referrals for Adults in Primary care]). METHOD: Between October 2012 and February 2014, participants were recruited through 23 primary care practices in England; 17 practices provided data on the characteristics of invited participants. RESULTS: Females were twice as likely as males to enrol in the trial (odds ratio [OR] 2.01, 95% confidence interval [CI] = 1.75 to 2.32). However, the proportion of males was threefold higher than seen in routine primary care referrals or similar trials that invited patients opportunistically. People from less deprived areas were more likely to enrol than those in more deprived areas (OR 1.77, 95% CI = 1.55 to 2.03). Older patients (>=40 years) were more likely to enrol than younger patients (OR 1.60, 95% CI = 1.34 to 1.91). CONCLUSION: Males, younger people, and those from more deprived areas were less likely to take up the invitation to participate in this trial. The gender bias was smaller than observed in routine practice, suggesting that a substantial proportion of the inequity observed previously is a consequence of bias with regard to the offer of intervention. This study suggests that a simple way to overcome much of the gender bias is to write to patients who are overweight and offer referral. Uptake of the invitation to participate was lower in groups of lower socioeconomic status suggesting the need to preferentially offer referrals to this group to reduce health inequalities and for research to explore barriers to uptake. PMID- 26906630 TI - Health characteristics and consultation patterns of people with intellectual disability: a cross-sectional database study in English general practice. AB - BACKGROUND: People with intellectual disability (ID) are a group with high levels of healthcare needs; however, comprehensive information on these needs and service use is very limited. AIM: To describe chronic disease, comorbidity, disability, and general practice use among people with ID compared with the general population. DESIGN AND SETTING: This study is a cross-sectional analysis of a primary care database including 408 English general practices in 2012. METHOD: A total of 14 751 adults with ID, aged 18-84 years, were compared with 86 221 age-, sex- and practice-matched controls. Depending on the outcome, prevalence (PR), risk (RR), or odds (OR) ratios comparing patients with ID with matched controls are shown. RESULTS: Patients with ID had a markedly higher prevalence of recorded epilepsy (18.5%, PR 25.33, 95% confidence interval [CI] = 23.29 to 27.57), severe mental illness (8.6%, PR 9.10, 95% CI = 8.34 to 9.92), and dementia (1.1%, PR 7.52, 95% CI = 5.95 to 9.49), as well as moderately increased rates of hypothyroidism and heart failure (PR>2.0). However, recorded prevalence of ischaemic heart disease and cancer was approximately 30% lower than the general population. The average annual number of primary care consultations was 6.29 for patients with ID, compared with 3.89 for matched controls. Patients with ID were less likely to have longer doctor consultations (OR 0.73, 95% CI = 0.69 to 0.77), and had lower continuity of care with the same doctor (OR 0.77, 95% CI = 0.73 to 0.82). CONCLUSION: Compared with the general population, people with ID have generally higher overall levels of chronic disease and greater primary care use. Ensuring access to high-quality chronic disease management, especially for epilepsy and mental illness, will help address these greater healthcare needs. Continuity of care and longer appointment times are important potential improvements in primary care. PMID- 26906631 TI - Kawasaki disease incidence in children and adolescents: an observational study in primary care. AB - BACKGROUND: Kawasaki disease is reported to be increasing in incidence and is the commonest childhood cause of acquired heart disease in the Western world. AIM: To determine the current UK incidence of Kawasaki disease across childhood and adolescence; and investigate trends over time and season. DESIGN AND SETTING: An observational, descriptive study in the UK. METHOD: The Health Improvement Network (THIN) database of primary healthcare records was searched for codes or text indicating Kawasaki disease. Identified records were compared with a study case definition and a date of onset was assigned to cases. The incidence, age/sex distribution, and trend in seasonal and temporal distribution were estimated (2008-2012). RESULTS: A total of 110 episodes of Kawasaki disease in 109 children were identified from 3.9 million person-years observation. The incidence of Kawasaki disease was 2.8 per 100 000 person-years (95% confidence interval [CI] = 2.3 to 3.4) when aged <20 years; 9.1 (95% CI = 7.3 to 11.2) aged <5 years, and 3.0 per 100 000 (95% CI = 2.0 to 4.3) across the age groups when possible cases were included. More cases were identified in males (55%) with one-fifth of cases diagnosed after 5 years of age. There was no statistically significant trend in incidence over the study years (P = 0.10 adjusted for sex and month), or between seasons (P = 0.65 adjusted for year and sex). CONCLUSION: Although the incidence of Kawasaki disease remains low and has stabilised in the UK, GPs should recognise that the condition occurs throughout childhood and across the seasons. PMID- 26906632 TI - A Shh coreceptor Cdo is required for efficient cardiomyogenesis of pluripotent stem cells. AB - Sonic hedgehog (Shh) signaling plays an important role for early heart development, such as heart looping and cardiomyogenesis of pluripotent stem cells. A multifunctional receptor Cdo functions as a Shh coreceptor together with Boc and Gas1 to activate Shh signaling and these coreceptors seem to play compensatory roles in early heart development. Thus in this study, we examined the role of Cdo in cardiomyogenesis by utilizing an in vitro differentiation of pluripotent stem cells. Here we show that Cdo is required for efficient cardiomyogenesis of pluripotent stem cells by activation of Shh signaling. Cdo is induced concurrently with Shh signaling activation upon induction of cardiomyogenesis of P19 embryonal carcinoma (EC) cells. Cdo-depleted P19 EC and Cdo(-/-) mouse embryonic stem (ES) cells display decreased expression of key cardiac regulators, including Gata4, Nkx2.5 and Mef2c and this decrease coincides with reduced Shh signaling activities. Furthermore Cdo deficiency causes a stark reduction in formation of mature contractile cardiomyocytes. This defect in cardiomyogenesis is overcome by reactivation of Shh signaling at the early specification stage of cardiomyogenesis. The Shh agonist treatment restores differentiation capacities of Cdo-deficient ES cells into contractile cardiomyocytes by recovering both the expression of early cardiac regulators and structural genes such as cardiac troponin T and Connexin 43. Therefore Cdo is required for efficient cardiomyogenesis of pluripotent stem cells and an excellent target to improve the differentiation potential of stem cells for generation of transplantable cells to treat cardiomyopathies. PMID- 26906633 TI - Expressing an inhibitor of PLCbeta1b sustains contractile function following pressure overload. AB - The activity of phospholipase Cbeta1b (PLCbeta1b) is selectively elevated in failing myocardium and cardiac expression of PLCbeta1b causes contractile dysfunction. PLCbeta1b can be selectively inhibited by expressing a peptide inhibitor that prevents sarcolemmal localization. The inhibitory peptide, PLCbeta1b-CT was expressed in heart from a mini-gene using adeno-associated virus (rAAV6-PLCbeta1b-CT). rAAV6-PLCbeta1b-CT, or blank virus, was delivered IV (4*10(9)vg/g body weight) and trans-aortic-constriction (TAC) or sham-operation was performed 8weeks later. Expression of PLCbeta1b-CT prevented the loss of contractile function, eliminated lung congestion and improved survival following TAC with either a 'moderate' or 'severe' pressure gradient. Hypertrophy was attenuated but not eliminated. Expression of the PLCbeta1b-CT peptide 2-3weeks after TAC reduced contractile dysfunction and lung congestion, without limiting hypertrophy. PLCbeta1b inhibition ameliorates pathological responses following acute pressure overload. The targeting of PLCbeta1b to the sarcolemma provides the basis for the development of a new class of inotropic agent. PMID- 26906635 TI - Shedding light on miR-26a: Another key regulator of angiogenesis in diabetic wound healing. PMID- 26906634 TI - Permissive role of AMPK and autophagy in adiponectin deficiency-accentuated myocardial injury and inflammation in endotoxemia. AB - BACKGROUND: Adiponectin (APN), an adipose-derived adipokine, alleviates lipopolysaccharide (LPS)-induced injury in multiple organs including hearts although the underlying mechanism in endotoxemia remains elusive. This study was designed to examine the role of adiponectin in LPS-induced cardiac anomalies and inflammation as well as the underlying mechanism with a focus on autophagy - a conserved machinery for bulk degradation of intracellular components. METHODS AND RESULTS: Wild-type (WT) and APN(-/-) mice were challenged with LPS (4mg/kg) or saline for 6h. Echocardiography, cardiomyocyte contractile and intracellular Ca(2+) properties were evaluated. Markers of autophagy, apoptosis and inflammation including LC3B, p62, Beclin1, AMPK, mTOR, ULK, Caspase 3, Bcl-2, Bax, TLR4, TRAF6, MyD88, IL-1B, TNFalpha, HMGB1, JNK and IkappaB were examined using Western blot or RT-PCR. Our results showed that LPS challenge reduced fractional shortening, compromised cardiomyocyte contractile capacity, intracellular Ca(2+) handling properties, apoptosis and inflammation, which were accentuated by adiponectin ablation. Adiponectin ablation unmasked the LPS induced cardiac remodeling (left ventricular end systolic diameter) and prolongation of cell shortening. The detrimental effects of adiponectin ablation were associated with dampened autophagy in response to LPS through an AMPK-mTOR ULK1-dependent mechanism. In vivo administration of AMPK activator AICAR or the autophagy inducer rapamycin effectively attenuated or obliterated LPS-induced and adiponectin deficiency-accentuated responses without affecting TLR4, TRAF6 and MyD88. CONCLUSIONS: The findings suggest that AMPK and autophagy may play a permissive role in the adiponectin deficiency-exacerbated cardiac dysfunction, apoptosis and inflammation under LPS challenge possibly at the post-TLR4 receptor level. PMID- 26906636 TI - Synthesis and bioactivities of novel piperazine-containing 1,5-Diphenyl-2-penten 1-one analogues from natural product lead. AB - A series of novel 1,5-Diphenyl-2-penten-1-one analogues (7a-h, 8a-h) with piperazine moiety have been designed and synthesized on the basis of natural product 1,5-Diphenyl-2-penten-1-one (I). All the synthesized compounds were evaluated in vitro for anti-plant pathogenic fungi activities and insecticidal activities. The results indicated that most of these analogues exhibited moderate antifungal activities and moderate to good insecticidal activities. Amongst them, the most potent 7c, 7e and 7h keep a mortality of 100% against larva of mosquito at the concentration of 1mg/L. Initial structure-activity relationship (SAR) analysis showed that, a methyl group can influence the biological activities of these compounds significantly, the compounds with N'-unsubstituted piperazine showed much better antifungal activities and larvicidal activity against mosquito than the compounds with N'-methylated piperazine. In addition, the larvicidal activity against mosquito had sharply decline when the substituent on benzene ring was changed from 4-position to 2 or 3-position. PMID- 26906637 TI - Inhibition of human DNA topoisomerase IIalpha by two novel ellipticine derivatives. AB - Ellipticine (5,11-dimethyl-6H-pyrido[4,3-b]carbazole) is an antineoplastic agent that intercalates into DNA and alters topoisomerase II activity. Unfortunately, this compound displays a number of adverse properties. Therefore, to investigate new ellipticine-based compounds for their potential as topoisomerase II-targeted drugs, we synthesized two novel derivatives, N-methyl-5-demethyl ellipticine (ET 1) and 2-methyl-N-methyl-5-demethyl ellipticinium iodide (ET-2). As determined by DNA decatenation and cleavage assays, ET-1 and ET-2 act as catalytic inhibitors of human topoisomerase IIalpha and are both more potent than the parent compound. Neither compound impairs the ability of the type II enzyme to bind its DNA substrate. Finally, the potency of ET-1 and ET-2 as catalytic inhibitors of topoisomerase IIalpha appears to be related to their ability to intercalate into the double helix. PMID- 26906639 TI - Modeling BAS Dysregulation in Bipolar Disorder. AB - Time series analysis is a technique that can be used to analyze the data from a single subject and has great potential to investigate clinically relevant processes like affect regulation. This article uses time series models to investigate the assumed dysregulation of affect that is associated with bipolar disorder. By formulating a number of alternative models that capture different kinds of theoretically predicted dysregulation, and by comparing these in both bipolar patients and controls, we aim to illustrate the heuristic potential this method of analysis has for clinical psychology. We argue that, not only can time series analysis elucidate specific maladaptive dynamics associated with psychopathology, it may also be clinically applied in symptom monitoring and the evaluation of therapeutic interventions. PMID- 26906638 TI - Individual and combined antiparasitic effect of six plant metabolites against Leishmania amazonensis and Trypanosoma cruzi. AB - Six plant metabolites including isobavachalcone (1), 4-hydroxylonchocarpine (2), and (E)-1-(2,2-dimethyl-2H-chromen-6-yl)-3-(4-hydroxyphenyl)prop-2-en-1-one (3), 6,8-(di-3-methyl-but-2-enyl)eriodictyol (4), damnacanthal (5), and buesgenine (6) were evaluated for their leishmanicidal and trypanocidal activities against intracellular amastigotes of Leishmania amazonensis and Trypanosoma cruzi. Compounds 2-4 and 6 displayed antileishmanial activity while 3 and 5 showed trypanocidal effect. The leishmanicidal activity of 6 was expressed with the lowest IC50 (5.70MUg/mL) whereas the most trypanocidal metabolite (5) showed its activity with IC50 at 11.14MUg/mL. In addition, antiprotozoal effect of mixtures of 1-6 prepared at different ratios (3:1, 1:1, and 1:3) was also investigated. Interestingly, 1 and 2 initially inactive against T. cruzi, displayed trypanocidal activities when mixed together. This activity increased when 3 (13.63MUg/mL) was combined with 1 in ratios 1:1 (10.01MUg/mL) and 3:1 (7.78MUg/mL). Moreover, the leishmanicidal effect of 4 against L. amazonensis increased in the mixture 6/4 (1:3). PMID- 26906640 TI - Cationic polycarbonate-grafted superparamagnetic nanoparticles with synergistic dual-modality antimicrobial activity. AB - We report a new class of antimicrobial nanomaterials with biodegradable cationic polycarbonates grafted on superparamagnetic nanoparticles. Our results have shown that end-functionalized cationic polycarbonates, synthesized by organocatalytic ring opening polymerization, can be grafted onto superparamagnetic MnFe2O4 nanoparticles via ligand exchange. In comparison with the individual building blocks, the core-shell hybrid nanoparticles led to improved antimicrobial activities in two ways: first, the cationic polycarbonates in a brush form afforded a greater charge density than that of free polymer chains, resulting in stronger interactions with bacterial surfaces. Second, the structural integration of the "soft" polycarbonate shell and the "hard" superparamagnetic core in the hybrid nanoparticles brings about a synergistic action of membrane disruption by the cationic shell and magnetic hyperthermia by the nanoparticle core. The combination of two physical killing mechanisms holds great promise in fighting against a broad spectrum of bacterial pathogens. PMID- 26906641 TI - Depression and post-traumatic stress disorder in child victims of sexual abuse: perceived social support as a protection factor. AB - Background Social support has been shown to play a protective role against the development of post-traumatic stress disorder (PTSD) and depression in individuals exposed to trauma. Aims The purpose of this study was to investigate the effect of perceived social support on depression and PTSD in child victims of sexual abuse and to determine the relationship between them. Method In total 182 victims of sexual abuse aged 6-18 at time of interview were assessed. Clinical interviews, the Children's Depression Inventory (CDI) and the Child Posttraumatic Stress Reaction Index (CPTS-RI) were used to assess children's psychological status, while the Perceived Social Support Scale-Revised (PSSS-R) was used to measure social support. Results Girls had significantly higher median CDI and CPTS-RI scores than boys, while no significant difference was determined between boys and girls in terms of PSSS-R scores. A statistically significant negative correlation was determined between CDI and PSSS-R scores, CPTS-RI scores and PSSS R scores in girls, while no significant correlation was identified in male victims. Conclusions In conclusion, we think that social support networks for victims of sexual abuse need to be broadened and increased, and that importance should be attached to protective approaches in that context. PMID- 26906643 TI - New rules on driver licensing for patients with obstructive sleep apnea: European Union Directive 2014/85/EU. PMID- 26906642 TI - A pivotal role of phosphatidylinositol 3-kinase in delaying of methyl jasmonate induced leaf senescence. AB - Phosphatidylinositol 3-kinase (PI3K) and its product PI3P are involved in plant development and stress responses. Our recent report has suggested that down regulation of PI3K activity accelerated leaf senescence induced by methyl jasmonate (MeJA) and suppressed the activation of vacuolar H(+)-ATPase (V ATPase). In vitro and in vivo experiment revealed that PI3K interact with VHA-B2. The inhibition of V-ATPase activity suppressed the vacuolar acidification and enhanced the stomatal opening, thereby accelerating MeJA-induced leaf senescence. It was shown that there is close relationship between PI3K and V-ATPase. However, the factor which initiates the PI3K-V-ATPase pathway needs further improvement, and the domain of VHA-B that binds to PI3K is still not clear enough. By using the Arabidopsis and MeJA as the research model, studies have been performed to investigate the upstream regulation of PI3K and downstream function of PI3K-V ATPase pathway in the plant senescence. PMID- 26906644 TI - Photochemical transformation of an iron(III)-arsenite complex in acidic aqueous solution. AB - Surface complexation between arsenious acid anions (As(III)) and ferric (hydr)oxides in water is important for the transformation and transfer of inorganic arsenic species. The mechanisms of formation and the photochemistry of dissolved Fe(III)-As(III) complexes in acidic aqueous solution are still unclear. Here, the photooxidation of As(III) in the presence of Fe(III) ions in acidic media has been investigated by laser flash and steady-state photolysis. At low arsenite concentrations (<1 mM), As(III) is oxidized by the OH radical generated by photolysis of the FeOH(2+) complex. At higher arsenite concentrations (>10 mM), photoactive Fe(III)-As(III) complexes are formed (phi~ 0.012). At all arsenite concentrations, a white FeAsO4 colloid is formed during As(III) photolysis in the presence of Fe(III) ions. Solid Fe(III)-As(III) complexes have been prepared and characterized, and the photochemical transformation of As(III) into As(V) in solid Fe(III)-As(III) complexes has been confirmed. These findings are important for a better understanding of the evolution of As(III) species under environmental conditions and should provide guidance for detoxification of As(III)-polluted water systems. PMID- 26906645 TI - Body mass index strongly impacts the diagnosis and incidence of heparin-induced thrombocytopenia in the surgical intensive care unit. AB - BACKGROUND: The obese state has been linked to several immune-mediated conditions. Our objective was to examine the association of body mass index (BMI) with the diagnosis of heparin-induced thrombocytopenia (HIT). METHODS: Prospectively collected data on patients in the surgical and cardiac intensive care unit suspected of having HIT between January 2007 and August 2014 were analyzed. Patients were categorized into five discrete BMI (kg/m) groups and compared. Data collected included Warkentin 4-T scores, antiplatelet factor 4 (anti-PF4OD) values, serotonin release assay values, and thromboembolic diseases. HIT positivity was defined as serotonin release assay value greater than 20%. RESULTS: Of 304 patients meeting inclusion criteria, mean (SD) age was 62.1 (16.5) years, 59% were male, and mean (SD) BMI was 27 (6) kg/m. Thirty-six (12%) were positive for HIT. Incidence of HIT increased progressively with BMI (0%, 8%, 11%, 19%, 36%; p < 0.001). Compared with patients with normal BMI, patients with a BMI of 30 kg/m to 39.9 kg/m had a 200% increase in the odds for HIT (odds ratio [OR], 2.94; 95% confidence interval [CI], 1.20-7.54; p = 0.019), while patients with a BMI of 40 kg/m or greater had a 600% increase (OR, 6.98; 95% CI, 1.59 28.2; p = 0.012). After regression analysis, BMI remained an independent predictor of the development of HIT (adjusted OR per kg/m, 1.08; 95% CI, 1.02 1.14; p = 0.010). Anti-PF4OD values greater than or equal to 2.0 also increased with BMI (p < 0.001). In-hospital mortality increased significantly with BMI above normal (p = 0.026). Warkentin 4-T scores, deep venous thrombosis, pulmonary embolism, and stroke incidence did not correlate with changes in BMI. CONCLUSION: Increasing BMI seems to be strongly associated with increased rates of HIT in intensive care unit patients. Obesity is an important new clinical variable for estimating the pretest probability of HIT, and patient "thickness" could be considered a fifth "T" of the 4-T scoring system. Additional biochemical work is indicated to decipher the role of obesity in this immune-mediated condition. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level III. PMID- 26906648 TI - Association between anorexia nervosa and type 2 diabetes in Sweden: Etiological clue for the primary prevention of type 2 diabetes. AB - AIM: Caloric restriction has been found to be protective against the development of type 2 diabetes mellitus (T2D) in experimental animal studies. However, studies examining this association in humans are limited. In the present study, we examined whether individuals with anorexia nervosa, one marker of severe caloric restriction in humans, have a low incidence of T2D by using several Swedish registries. METHODS: Individuals with anorexia nervosa were identified from the Swedish Hospital Discharge Register and Outpatient Register between 1964 and 2010. Standardized incidence ratios (SIRs) for T2D were studied among individuals with anorexia nervosa compared to those without the disorder. RESULTS: A total of 17,135 individuals were identified with anorexia nervosa in Sweden. From this tally, 34 of them developed T2D, demonstrating a reduced risk of T2D with a SIR of 0.70, compared to individuals without anorexia nervosa. Patients with severe anorexia, indicated by more frequent hospitalizations, had a statistically non-significant lower incidence of T2D than those with fewer hospitalizations. A sibling study, controlled for familial confounding, found a statistically non-significant association between anorexia nervosa and T2D. CONCLUSION: Our study found that severe caloric restriction by using individuals with anorexia nervosa as a proxy was negatively associated with T2D, which might provide a biological basis for the primary prevention of T2D. Further studies are needed to explore whether moderate caloric restriction can effectively prevent the development of T2D in general population. PMID- 26906649 TI - Extensively Drug-Resistant Tuberculosis: Principles of Resistance, Diagnosis, and Management. AB - Extensively drug-resistant (XDR) tuberculosis (TB) is an unfortunate by-product of mankind's medical and pharmaceutical ingenuity during the past 60 years. Although new drug developments have enabled TB to be more readily curable, inappropriate TB management has led to the emergence of drug-resistant disease. Extensively drug-resistant TB describes Mycobacterium tuberculosis that is collectively resistant to isoniazid, rifampin, a fluoroquinolone, and an injectable agent. It proliferates when established case management and infection control procedures are not followed. Optimized treatment outcomes necessitate time-sensitive diagnoses, along with expanded combinations and prolonged durations of antimicrobial drug therapy. The challenges to public health institutions are immense and most noteworthy in underresourced communities and in patients coinfected with human immunodeficiency virus. A comprehensive and multidisciplinary case management approach is required to optimize outcomes. We review the principles of TB drug resistance and the risk factors, diagnosis, and managerial approaches for extensively drug-resistant TB. Treatment outcomes, cost, and unresolved medical issues are also discussed. PMID- 26906650 TI - Healthy Lifestyle Characteristics and Their Joint Association With Cardiovascular Disease Biomarkers in US Adults. AB - OBJECTIVE: To estimate the prevalence of healthy lifestyle characteristics and to examine the association between different combinations of healthy lifestyle characteristics and cardiovascular disease biomarkers. PATIENTS AND METHODS: The prevalence of healthy lifestyle characteristics was estimated for the US adult population (N=4745) using 2003-2006 National Health and Nutrition Examination Survey data for the following parameters: being sufficiently active (accelerometer), eating a healthy diet (Healthy Eating Index based on 24-hour recalls), being a nonsmoker (serum cotinine level), and having a recommended body fat percentage (dual-energy X-ray absorptiometry). Cardiovascular biomarkers included mean arterial pressure, C-reactive protein, white blood cells (WBCs), total cholesterol, high-density lipoprotein cholesterol (HDL-C), total cholesterol to HDL-C ratio, fasting low-density lipoprotein cholesterol, fasting triglycerides, fasting glucose, fasting insulin, insulin resistance, hemoglobin A1c, and homocysteine. The study was conducted from August 15, 2013, through January 5, 2016. RESULTS: Only 2.7% (95% CI, 1.9%-3.4%) of all adults had all 4 healthy lifestyle characteristics. Participants with 3 or 4 compared with 0 healthy lifestyle characteristics had more favorable biomarker levels except for mean arterial blood pressure, fasting glucose, and hemoglobin A1c. Having at least 1 or 2 compared with 0 healthy lifestyle characteristics was favorably associated with C-reactive protein, WBCs, HDL-C, total cholesterol, and homocysteine. For HDL-C and total cholesterol, the strongest correlate was body fat percentage. For homocysteine, a healthy diet and not smoking were strong correlates; for WBCs, diet was not a strong correlate. CONCLUSION: Although multiple healthy lifestyle characteristics are important, specific health characteristics may be more important for particular cardiovascular disease risk factors. PMID- 26906651 TI - 72-Year-Old Woman With Redness, Swelling, and Pain of the Forearms and Hands. PMID- 26906652 TI - An ambitious agenda for humanity. PMID- 26906653 TI - UK welfare reform: disastrous for the poorest children. PMID- 26906654 TI - UK guidance on human-animal hybrid research. PMID- 26906655 TI - New WHO guidelines on emergency triage assessment and treatment. PMID- 26906657 TI - Xueqing Yu: a driving force in Chinese nephrology. PMID- 26906658 TI - Do not forget the orphan children of Syria. PMID- 26906659 TI - Assessment of sequelae of torture for refugees in host countries. PMID- 26906660 TI - Immunosuppression for management of Crohn's disease. PMID- 26906661 TI - Immunosuppression for management of Crohn's disease. PMID- 26906662 TI - Pre-hospital emergency medicine: pain control. PMID- 26906663 TI - Immunosuppression for management of Crohn's disease - Author's reply. PMID- 26906664 TI - Helicobacter pylori vaccination. PMID- 26906665 TI - Implementing health policy and systems research in Myanmar. PMID- 26906666 TI - Helicobacter pylori vaccination - Authors' reply. PMID- 26906667 TI - Prepublication culture in clinical research. PMID- 26906668 TI - Progress of clinical practice on the management of burn-associated pain: Lessons from animal models. AB - Opioid-based analgesics provide the mainstay for attenuating burn pain, but they have a myriad of side effects including respiratory depression, nausea, impaired gastrointestinal motility, sedation, dependence, physiologic tolerance, and opioid-induced hyperalgesia. To test and develop novel analgesics, validated burn relevant animal models of pain are indispensable. Herein we review such animal models, which are mostly limited to rodent models of burn-induced, inflammatory, and neuropathic pain. The latter two are pain syndromes that provide insight into the pain caused by systemic pro-inflammatory cytokines and direct injury to nerves (e.g., after severe burn), respectively. To date, no single animal model optimally mimics the complex pathophysiology and pain that a human burn patient experiences. No currently available burn-pain model examines effects of pharmacological intervention on wound healing. As cornerstones of pain and wound healing, pro-inflammatory mediators may be utilized for insight into both processes. Moreover, common clinical concerns such as systemic inflammatory response syndrome and multiple organ dysfunction remain unaddressed. For development of analgesics, these aberrations can significantly alter the potential efficacy and/or adverse effects of a prescribed analgesic following burn trauma. We therefore suggest that a multi-model strategy would be the most clinically relevant when evaluating novel analgesics for use in burn patients. PMID- 26906669 TI - A case of Tannerite((r)) target mixture causing severe blast injury. AB - Tannerite((r)) is a proprietary blend of an oxidizer, ammonium nitrate, and aluminum powder catalyst used to make homemade exploding targets. While it is currently approved for unrestricted sale in the United States, it can be used to form devices capable of inflicting major blast injury. We present here a case of close proximity exposure to detonation of the mixed Tannerite((r)) blend. In our patient, the exposure lead to injuries typical of blast injury, such as tympanic membrane rupture, globe injury, and severe burns. We review here the sequelae of blast injuries that one must consider when treating a patient with close proximity exposure to Tannerite, with considerations unique to this product. PMID- 26906670 TI - The intertropical convergence zone modulates intense hurricane strikes on the western North Atlantic margin. AB - Most Atlantic hurricanes form in the Main Development Region between 9 degrees N to 20 degrees N along the northern edge of the Intertropical Convergence Zone (ITCZ). Previous research has suggested that meridional shifts in the ITCZ position on geologic timescales can modulate hurricane activity, but continuous and long-term storm records are needed from multiple sites to assess this hypothesis. Here we present a 3000 year record of intense hurricane strikes in the northern Bahamas (Abaco Island) based on overwash deposits in a coastal sinkhole, which indicates that the ITCZ has likely helped modulate intense hurricane strikes on the western North Atlantic margin on millennial to centennial-scales. The new reconstruction closely matches a previous reconstruction from Puerto Rico, and documents a period of elevated intense hurricane activity on the western North Atlantic margin from 2500 to 1000 years ago when paleo precipitation proxies suggest that the ITCZ occupied a more northern position. Considering that anthropogenic warming is predicted to be focused in the northern hemisphere in the coming century, these results provide a prehistoric analog that an attendant northern ITCZ shift in the future may again return the western North Atlantic margin to an active hurricane interval. PMID- 26906674 TI - Epileptic Seizure Detection with Log-Euclidean Gaussian Kernel-Based Sparse Representation. AB - Epileptic seizure detection plays an important role in the diagnosis of epilepsy and reducing the massive workload of reviewing electroencephalography (EEG) recordings. In this work, a novel algorithm is developed to detect seizures employing log-Euclidean Gaussian kernel-based sparse representation (SR) in long term EEG recordings. Unlike the traditional SR for vector data in Euclidean space, the log-Euclidean Gaussian kernel-based SR framework is proposed for seizure detection in the space of the symmetric positive definite (SPD) matrices, which form a Riemannian manifold. Since the Riemannian manifold is nonlinear, the log-Euclidean Gaussian kernel function is applied to embed it into a reproducing kernel Hilbert space (RKHS) for performing SR. The EEG signals of all channels are divided into epochs and the SPD matrices representing EEG epochs are generated by covariance descriptors. Then, the testing samples are sparsely coded over the dictionary composed by training samples utilizing log-Euclidean Gaussian kernel-based SR. The classification of testing samples is achieved by computing the minimal reconstructed residuals. The proposed method is evaluated on the Freiburg EEG dataset of 21 patients and shows its notable performance on both epoch-based and event-based assessments. Moreover, this method handles multiple channels of EEG recordings synchronously which is more speedy and efficient than traditional seizure detection methods. PMID- 26906675 TI - Identifying the characteristics, natural behavioral pattern, and response to therapy in ITP in a multi-center population in Sri Lanka. AB - OBJECTIVE: To describe some selected characteristics of immune thrombocytopenia (ITP) such as presentation, the disease pattern, treatment options, and response to therapy and side effects to common therapeutic options. METHODS: A group of 72 patients diagnosed as ITP were studied over a period of 5 years in two main centers in Sri Lanka. Characteristics of the disease such as presentation, the disease pattern, treatment options, and response to therapy and side effects to common therapeutic options were studied. RESULTS: The ages of the patients ranged from 12 to 71 years but the majority (64.2%) were between 20 and 45 years. In 47 (65.3%) the average platelet count at presentation was below 30 * 10(9)/l and in these patients there was a significant increase in bleeding manifestations. Sixty nine patients were given steroids as the initial treatment and all had responded initially. Time to respond ranged from 3 to 30 days with an average of 11 days. Twenty-four patients developed steroid-related side effects. In 24 patients second-line treatment options such as dapsone, azathioprine, and danazole were given but a satisfactory response to them could not be demonstrated. DISCUSSION: The heterogeneous behavioral patterns of the disease with patients who are having the same platelet count (<30 * 10(9)/l) were observed and this revealed that ITP needs an individualized approach regardless of the platelet count of the patient. A close follow-up of the patients revealed that the patient's understanding of the disease and ability to identify the warning signs resulted in less intervention with drugs which lead to many harmful long-term side effects. PMID- 26906678 TI - Peer review in the cloud. PMID- 26906676 TI - Graded and discontinuous EphA-ephrinB expression patterns in the developing auditory brainstem. AB - Eph-ephrin interactions guide topographic mapping and pattern formation in a variety of systems. In contrast to other sensory pathways, their precise role in the assembly of central auditory circuits remains poorly understood. The auditory midbrain, or inferior colliculus (IC) is an intriguing structure for exploring guidance of patterned projections as adjacent subdivisions exhibit distinct organizational features. The central nucleus of the IC (CNIC) and deep aspects of its neighboring lateral cortex (LCIC, Layer 3) are tonotopically-organized and receive layered inputs from primarily downstream auditory sources. While less is known about more superficial aspects of the LCIC, its inputs are multimodal, lack a clear tonotopic order, and appear discontinuous, terminating in modular, patch/matrix-like distributions. Here we utilize X-Gal staining approaches in lacZ mutant mice (ephrin-B2, -B3, and EphA4) to reveal EphA-ephrinB expression patterns in the nascent IC during the period of projection shaping that precedes hearing onset. We also report early postnatal protein expression in the cochlear nuclei, the superior olivary complex, the nuclei of the lateral lemniscus, and relevant midline structures. Continuous ephrin-B2 and EphA4 expression gradients exist along frequency axes of the CNIC and LCIC Layer 3. In contrast, more superficial LCIC localization is not graded, but confined to a series of discrete ephrin-B2 and EphA4-positive Layer 2 modules. While heavily expressed in the midline, much of the auditory brainstem is devoid of ephrin-B3, including the CNIC, LCIC Layer 2 modular fields, the dorsal nucleus of the lateral lemniscus (DNLL), as well as much of the superior olivary complex and cochlear nuclei. Ephrin-B3 LCIC expression appears complementary to that of ephrin-B2 and EphA4, with protein most concentrated in presumptive extramodular zones. Described tonotopic gradients and seemingly complementary modular/extramodular patterns suggest Eph-ephrin guidance in establishing juxtaposed continuous and discrete neural maps in the developing IC prior to experience. PMID- 26906677 TI - Can place-specific cochlear dispersion be represented by auditory steady-state responses? AB - The present study investigated to what extent properties of local cochlear dispersion can be objectively assessed through auditory steady-state responses (ASSR). The hypothesis was that stimuli compensating for the phase response at a particular cochlear location generate a maximally modulated basilar membrane (BM) response at that BM position, due to the large "within-channel" synchrony of activity. This would lead, in turn, to a larger ASSR amplitude than other stimuli of corresponding intensity and bandwidth. Two stimulus types were chosen: 1] Harmonic tone complexes consisting of equal-amplitude tones with a starting phase following an algorithm developed by Schroeder [IEEE Trans. Inf. Theory 16, 85-89 (1970)] that have earlier been considered in behavioral studies to estimate human auditory filter phase responses; and 2] simulations of auditory-filter impulse responses (IR). In both cases, also the temporally reversed versions of the stimuli were considered. The ASSRs obtained with the Schroeder tone complexes were found to be dominated by "across-channel" synchrony and, thus, do not reflect local place-specific information. In the case of the more frequency specific stimuli, no significant differences were found between the responses to the IR and its temporally reversed counterpart. Thus, whereas ASSRs to narrowband stimuli have been used as an objective indicator of frequency-specific hearing sensitivity, the method does not seem to be sensitive enough to reflect local cochlear dispersion. PMID- 26906679 TI - Analysis of five years of controlled access and data sharing compliance at the International Cancer Genome Consortium. PMID- 26906673 TI - Diabetes and Kidney Disease: Role of Oxidative Stress. AB - SIGNIFICANCE: Intrarenal oxidative stress plays a critical role in the initiation and progression of diabetic kidney disease (DKD). Enhanced oxidative stress results from overproduction of reactive oxygen species (ROS) in the context of concomitant, insufficient antioxidant pathways. Renal ROS production in diabetes is predominantly mediated by various NADPH oxidases (NOXs), but a defective antioxidant system as well as mitochondrial dysfunction may also contribute. Recent Advances: Effective agents targeting the source of ROS generation hold the promise to rescue the kidney from oxidative damage and prevent subsequent progression of DKD. Critical Issues and Future Directions: In the present review, we summarize and critically analyze molecular and cellular mechanisms that have been demonstrated to be involved in NOX-induced renal injury in diabetes, with particular focus on the role of increased glomerular injury, the development of albuminuria, and tubulointerstitial fibrosis, as well as mitochondrial dysfunction. Furthermore, novel agents targeting NOX isoforms are discussed. Antioxid. Redox Signal. 25, 657-684. PMID- 26906680 TI - Enabling direct fate conversion with network biology. AB - Current efforts in cellular disease modeling and regenerative medicine are limited by the paucity of cell types that can be generated in the laboratory. A new study introduces a computational framework, Mogrify, that uses network biology to predict combinations of transcription factors necessary for direct conversion between human cell types to ameliorate this issue. PMID- 26906681 TI - Birth and upgrowth of the Hox topological domains during evolution. AB - The recently discovered chromatin compartments called topologically associating domains (TADs) are essential for the three-dimensional organization of regulatory interactions driving gene expression. A new study documents the emergence of a TAD flanking the amphioxus Hox cluster, prefiguring the vertebrate anterior Hox TAD and preceding the appearance of the concurring posterior Hox TAD. PMID- 26906682 TI - Biodiversity and hypervirulence of Listeria monocytogenes. AB - The integration of large, well-sampled collections of bacterial isolates with genomics and experimental methods provides opportunities for 'top-down' discovery of the genetic basis of phenotypes of interest. In a new report, the authors apply this approach to investigate the heterogeneity in manifestations of disease caused by Listeria monocytogenes and demonstrate that a previously uncharacterized cellobiose PTS system is involved in central nervous system infection. PMID- 26906683 TI - The role of taurine in improving neural stem cells proliferation and differentiation. AB - OBJECTIVES: Taurine is one of the most abundant amino acids in the central nervous system and has important functions in the promotion of brain development. This study aimed to determine the mechanistic role of taurine in improving neuronal proliferation, stem cell proliferation, and neural differentiation. METHODS: The data for this review were primarily retrieved from the PubMed database from 1985 to 2015 in English. The search string included the keywords taurine, brain development, neuronal, stem cell, proliferation, differentiation, and others. Relevant publications were identified, retrieved, and reviewed. RESULTS: This review introduces the source, function, and mechanisms of taurine in brain development and provides additional detail regarding the mechanistic role of taurine in improving neuronal proliferation, stem cell proliferation, and neural differentiation. Many studies concerning these aspects are discussed. CONCLUSIONS: Taurine plays an important role in brain development, including neuronal proliferation, stem cell proliferation, and differentiation, via several mechanisms. Taurine can be directly used in clinical applications to improve brain development because it has no toxic effects on humans. PMID- 26906684 TI - Broad temperature range of cubic blue phase present in simple binary mixture systems containing rodlike Schiff base mesogens with tolane moiety. AB - Four simple rodlike Schiff base mesogens with tolane moiety were synthesized and applied to stabilize cubic blue phases (BPs) in simple binary mixture systems for the first time. When the chiral additive or was added into a chiral salicylaldimine-based compound, the temperature range of the cubic BP could be extended by more than 20 degrees C. However, when the chiral Schiff base mesogen was blended with chiral dopant possessing opposite handedness, , BPs could not be observed. Interestingly, the widest temperature range of the cubic BPs (~35 degrees C) could be induced by adding the rodlike chiral dopant or into the rodlike racemic Schiff base mesogen with hydroxyl group. On the basis of our experimental results and molecular modeling, the appearance and temperature range of the BPs are affected by the dipole moment and the biaxiality of the molecular geometry. Accordingly, we demonstrated that the hydroxyl group and the methyl branch in this type of Schiff base mesogen play an important role in the stabilization of BPs. PMID- 26906686 TI - Are We Really Patient Focused? Time to Challenge Ourselves. PMID- 26906685 TI - Diagnostic accuracy of neurophysiological criteria for early diagnosis of AIDP: A prospective study. AB - OBJECTIVE: To assess the diagnostic accuracy of electrodiagnostic (EDX) criteria for the early detection and characterization of Guillain-Barre syndrome (GBS) in clinical practice. METHODS: We conducted a prospective study in patients referred for an EDX exam with clinical suspicion of GBS. We evaluated four sets of neurophysiological criteria and four neurophysiological tests among those recently proposed for the early diagnosis of GBS. RESULTS: We recruited 84 patients. Acute inflammatory demyelinating polyneuropathy (AIDP) was the final diagnosis in 23 patients. No axonal forms were found. The best sensitivity was obtained using Rajabally et al.'s criteria (82.1%), whereas the specificity was 90.0% for Ho et al.'s and Hadden et al.'s criteria and 100% for the Dutch GBS study group and Rajabally's criteria. Regarding the neurophysiological tests proposed for early diagnosis, the sensitivity ranged from 16.6 to 100%, whereas specificity ranged from 73.1 to 98.3%. CONCLUSION: The Dutch GBS study group and Rajabally et al.'s criteria showed an optimal combination of sensitivity and specificity for clinical practice, although with a slightly higher sensitivity for Rajabally et al.'s criteria. None of the neurophysiological parameters recently proposed for early diagnosis have good diagnostic accuracy for clinical application. SIGNIFICANCE: In a real clinical setting with patients referred by neurologists and emergency doctors, an EDX study performed within a week of symptom onset supports the diagnosis of AIDP in 82% of cases. PMID- 26906687 TI - Patient and Family Engagement Summit: Needed Changes in Clinical Practice. AB - Patient and family engagement is a strategy to enhance healthcare outcomes through strong clinician-patient partnerships. A new care delivery process, in which the patient is the driver of the healthcare team, is required to achieve optimal health. A summit partially funded by a seed grant from the Robert Wood Johnson Executive Nurse Fellow Alumni Foundation was held with interprofessional colleagues and patient representatives to identify needed clinical competencies and future practice changes. Recommended shifts in the care delivery process included a focus on patient strengths, including the patient as a valued team member, doing care "with me" and not "to me," and considering all entities or providers including the patient, as equal partners. PMID- 26906688 TI - Nurse Manager Competencies Supporting Patient Engagement. AB - Patient engagement is an important element in transitioning care delivery to achieve population health management goals. Providers are challenged to develop care delivery processes that better engage patients in their life journey across the healthcare continuum. Nurse leaders are central to this process. Building upon the American Organization of Nurse Executives competencies for nurse executives, the nurse manager role requires specific skills to translate the vision of patient engagement into practice. PMID- 26906689 TI - Interactive Care Model: A Framework for More Fully Engaging People in Their Healthcare. AB - Transformation of care delivery requires rethinking the relationship between the person and clinician. The model described provides a process to more fully engage patients in their care. Five encounters include assessing capacity for engagement, exchanging information and choices, planning, determining interventions, and evaluating the effectiveness of engagement interventions. Created by researchers and validated by experts, implications for practice, education, and policy are explored. PMID- 26906690 TI - [Methicillin-resistant Staphylococcus aureus carrying the mecC gene: an emerging problem?]. PMID- 26906691 TI - DNA base-stacking assay utilizing catalytic hairpin assembly-induced gold nanoparticle aggregation for colorimetric protein sensing. AB - A label-free and enzyme-free colorimetric sensing platform for the amplified detection of fibronectin was developed based on an ingenious combination of catalytic hairpin assembly and a base stacking hybridization-based gold nanoparticle aggregation strategy. The detection limit of 2.3 pM is at least one order of magnitude lower than that of established fibronectin biosensors. PMID- 26906692 TI - Differential distribution and titre of selected grapevine leafroll-associated virus 3 genetic variants within grapevine rootstocks. AB - In this study of three grapevine leafroll-associated virus 3 (GLRaV-3) genetic variants in two grapevine rootstock hosts, GLRaV-3 detection was shown to be affected by the virus distribution, titre, and the genetic variant. Group VI and NZ2 GLRaV-3 variants had reduced detectability compared with the group I variant. Differences in the genomic and subgenomic RNA (sgRNA) expression levels, and differences in the level of expression between the genetic variants were also observed. The observed differences in virus titre and sgRNA expression levels suggest differences in plant-virus interactions by the various GLRaV-3 genetic variants. PMID- 26906693 TI - Molecular epidemiology of noroviruses associated with sporadic gastroenteritis in Guangzhou, China, 2013-2015. AB - Norovirus diarrhea is a great threat to public health worldwide. To characterize the prevalence of circulating noroviruses associated with sporadic gastroenteritis cases in Guangzhou, 215 stool specimens were collected during two consecutive cold seasons in 2013-2015. Noroviruses were detected in 25 (11.63 %) samples, and GII.4 (6/9) and GII.17 (10/16) were identified as the most predominant variants of each of those seasons. The remaining strains belonged to the genotypes GII.P12/GII.3, GII.2, and GI.Pb/GI.6. The phylogenetic relationships of the GII.17 strains were analyzed based on their capsid protein sequences. This study suggests a significant shift of predominant variants associated with sporadic gastroenteritis in Guangzhou. PMID- 26906694 TI - The complete nucleotide sequence of pelargonium leaf curl virus. AB - Investigation of a tombusvirus isolated from tulip plants in Scotland revealed that it was pelargonium leaf curl virus (PLCV) rather than the originally suggested tomato bushy stunt virus. The complete sequence of the PLCV genome was determined for the first time, revealing it to be 4789 nucleotides in size and to have an organization similar to that of the other, previously described tombusviruses. Primers derived from the sequence were used to construct a full length infectious clone of PLCV that recapitulates the disease symptoms of leaf curling in systemically infected pelargonium plants. PMID- 26906695 TI - Interferon-inducible GTPase: a novel viral response protein involved in rabies virus infection. AB - Rabies virus infection is a major public health concern because of its wide host interference spectrum and nearly 100 % lethality. However, the interactions between host and virus remain unclear. To decipher the authentic response in the central nervous system after rabies virus infection, a dynamic analysis of brain proteome alteration was performed. In this study, 104 significantly differentially expressed proteins were identified, and intermediate filament, interferon-inducible GTPases, and leucine-rich repeat-containing protein 16C were the three outstanding groups among these proteins. Interferon-inducible GTPases were prominent because of their strong upregulation. Moreover, quantitative real time PCR showed distinct upregulation of interferon-inducible GTPases at the level of transcription. Several studies have shown that interferon-inducible GTPases are involved in many biological processes, such as viral infection, endoplasmic reticulum stress response, and autophagy. These findings indicate that interferon-inducible GTPases are likely to be a potential target involved in rabies pathogenesis or the antiviral process. PMID- 26906696 TI - Quantifying volume reduction and peak flow mitigation for three bioretention cells in clay soils in northeast Ohio. AB - Green infrastructure aims to restore watershed hydrologic function by more closely mimicking pre-development groundwater recharge and evapotranspiration (ET). Bioretention has become a popular stormwater control due to its ability to reduce runoff volume through these pathways. Three bioretention cells constructed in low permeability soils in northeast Ohio were monitored for non-winter quantification of inflow, drainage, ET, and exfiltration. The inclusion of an internal water storage (IWS) zone allowed the three cells to reduce runoff by 59%, 42%, and 36% over the monitoring period, in spite of the tight underlying soils. The exfiltration rate and the IWS zone thickness were the primary determinants of volume reduction performance. Post-construction measured drawdown rates were higher than pre-construction soil vertical hydraulic conductivity tests in all cases, due to lateral exfiltration from the IWS zones and ET, which are not typically accounted for in pre-construction soil testing. The minimum rainfall depths required to produce outflow for the three cells were 5.5, 7.4, and 13.8mm. During events with 1-year design rainfall intensities, peak flow reduction varied from 24 to 96%, with the best mitigation during events where peak rainfall rate occurred before the centroid of the rainfall volume, when adequate bowl storage was available to limit overflow. PMID- 26906697 TI - Assessing the contribution of combustion-derived contaminants to a remote subarctic environment from traffic on the Tibbitt to Contwoyto winter road (Northwest Territories, Canada). AB - Remote mining operations in Canada's Northwest Territories and Nunavut are supported by a 600 km winter road, which spans the transition from subarctic boreal forest in Yellowknife to low Arctic tundra. Each year, thousands of truckloads of fuel, large equipment, and other heavy loads are hauled up the winter road. We investigated whether diesel emissions from commercial truck traffic is a major source of metals and polycyclic aromatic compounds (PACs) to aquatic ecosystems along the winter road. In March 2014, at the end of the hauling season, we collected integrated snow samples, water, and sediment from nine lakes located along the winter road, as well as from six lakes located within the city of Yellowknife. Examination of PAC composition and diagnostic ratios in snow samples showed that wildfires are an important source of PACs to lakes along the winter road, while anthropogenic sources are more prevalent in snow from Yellowknife lakes. Concentrations of PACs, including those associated with diesel emissions, were variable in snow, water, and sediment across all sites. The highest concentrations of PACs in snow were reported in winter road lakes located in the subarctic boreal forest, where forest fires are common. No compositional differences were observed for PACs in sediment and water samples between Yellowknife and winter road lakes. We did not observe any evidence of metal contamination in snow collected along the winter road, and metal concentrations in snow from winter road sites were consistently lower than Yellowknife sites. Our results show that a high contribution of PACs from natural sources can obscure potential contributions from diesel traffic emissions along the winter road. PMID- 26906698 TI - Increasing trends of dissolved organic nitrogen (DON) in temperate forests under recovery from acidification in Flanders, Belgium. AB - We evaluated trends (2005-2013) and patterns of dissolved organic nitrogen (DON) and its ratio with dissolved organic carbon (DOC), DOC:DON in atmospheric deposition and soil solution of five Level II plots of the International Co operative Programme on Assessment and Monitoring of Air Pollution Effects on Forests (ICP Forests) in Flanders, Northern Belgium. The primary aim was to confirm positive postulated trends in DON levels and DOC:DON under on-going recovery from acidification. The DON concentrations (0.95-1.41 mg L(-1)) and fluxes (5.6-8.3 kg ha(-1)y(-1)) in throughfall were about twice as high compared to precipitation in the open field (0.40-0.48 mg L(-1), 3.0-3.9 kg ha(-1)y(-1)). Annual soil profile leaching losses of DON varied between 1.2 and 3.7 kg ha(-1)y( 1). The highest soil DON concentrations and fluxes were observed beneath the O horizon (1.84-2.36 mg L(-1), 10.1-12.3 kg ha(-1)y(-1)). Soil solution concentrations and fluxes of DON showed significant increasing trends. Temporarily soil solution DOC:DON rose following an exceptionally long spring drought in 2007, suggesting an effect of drying and rewetting on DOM composition. Further research is needed to test the dependence of DON and DOC:DON on factors such as latitude, forest cover, length of the growing season, hydrology and topography. Nonetheless, even with considerable variation in soil type, level of base saturation, and soil texture in the five included ICP Forests Level II plots, all data revealed a proportionally larger positive response of DON flux than DOC to recovery from acidification. PMID- 26906699 TI - The environmental cost of subsistence: Optimizing diets to minimize footprints. AB - The question of how to minimize monetary cost while meeting basic nutrient requirements (a subsistence diet) was posed by George Stigler in 1945. The problem, known as Stigler's diet problem, was famously solved using the simplex algorithm. Today, we are not only concerned with the monetary cost of food, but also the environmental cost. Efforts to quantify environmental impacts led to the development of footprint (FP) indicators. The environmental footprints of food production span multiple dimensions, including greenhouse gas emissions (carbon footprint), nitrogen release (nitrogen footprint), water use (blue and green water footprint) and land use (land footprint), and a diet minimizing one of these impacts could result in higher impacts in another dimension. In this study based on nutritional and population data for the United States, we identify diets that minimize each of these four footprints subject to nutrient constraints. We then calculate tradeoffs by taking the composition of each footprint's minimum diet and calculating the other three footprints. We find that diets for the minimized footprints tend to be similar for the four footprints, suggesting there are generally synergies, rather than tradeoffs, among low footprint diets. Plant based food and seafood (fish and other aquatic foods) commonly appear in minimized diets and tend to most efficiently supply macronutrients and micronutrients, respectively. Livestock products rarely appear in minimized diets, suggesting these foods tend to be less efficient from an environmental perspective, even when nutrient content is considered. The results' emphasis on seafood is complicated by the environmental impacts of aquaculture versus capture fisheries, increasing in aquaculture, and shifting compositions of aquaculture feeds. While this analysis does not make specific diet recommendations, our approach demonstrates potential environmental synergies of plant- and seafood based diets. As a result, this study provides a useful tool for decision-makers in linking human nutrition and environmental impacts. PMID- 26906700 TI - [Objective evaluation the application of femtosecond laser in cataract surgery]. AB - Femtosecond laser-assisted cataract surgery (FLACS) is a novel technology and the biggest revolution in the field of cataract in the latest several years. However, increasing large-scale population randomized controlled trials (RCT) have demonstrated that FLACS does not provide significant advantages over conventional phacoemulsification cataract surgery (CPCS) for common cataract patients. Furthermore, the cost and space requirement of the femtosecond equipment are another two limitations for the universal application of FSL in cataract surgery. However, FLACS may be beneficial for complex cataract situations, such as lens dislocation, zonular laxity, traumatic cataract, low preoperative endothelial cell values, and significant corneal astigmatism. With the progress of science and technology, FLACS can be expected to achieve integration with phacoemulsification systems, and equipment costs can be reduced, making it more widely used in clinical practice in the future. PMID- 26906701 TI - [Emphasis on the application of precision medicine in ophthalmology]. AB - Accompany with dramatically growth of large-scale biological databases (such as human genome sequence), improvement of life science and development of international clinical trials, science offers great potential for improving health care through precision medicine. As a hot topic recently, precision medicine might launch a revolution of the methodology in medical research. How to achieve precision medicine in clinical ophthalmology by means of biological data mining is a challenge for ophthalmologist-scientists. The best approach for advanced individual medicine is to buildup the digital ophthalmology, which includes human eye biobank, national biological databases network, clinical department, basic research lab, and international clinical trial center. The system of digital ophthalmology could explore the methods for ophthalmology research, integrate the source of eye biologic databases, promote international cooperation, and thus eventually supply the opportunity for translational medicine. PMID- 26906702 TI - [The pros and cons of femtosecond laser-assisted cataract surgery]. AB - Femtosecond laser-assisted cataract surgery (FLACS) is known as an innovative new technology. Compared with traditional surgical approach, FLACS is more accurate, more predictable and less energy used. However, in the current stage of development, there still may be intraoperative and postoperative complications, or even serious complications. FLACS has obvious advantages in certain surgical steps, but there are still clear disadvantages, so it still cannot completely replace the traditional phacoemulsification surgery. PMID- 26906703 TI - [Clinic analysis of femtosecond laser-assisted cataract surgery]. AB - OBJECTIVE: To evaluate the safety and effectiveness of femtosecond laser-assisted cataract surgery. METHODS: The interventional case series enrolled 314 eyes undergoing cataract surgery in Xiamen Ophthalmic Center between April and December 2013, patients were randomized to femtosecond laser-assisted cataract surgery(153 eyes) and conventional phacoemulsification cataract surgery(161 eyes). The clincic parameters of preoperation, during operation and postoperation were compared and statistically studied. Quantitative data were analyzed using the analysis of variance, independent t tests. Qualitative datawere analyzed using the crosstabs analysis chi-square test or the Fisher's exact test. RESULTS: The patient's demographics parameters(age, gender, IOP, axial length, mean keratometry, AC depth, Cataract grade) did not differ significantly between groups (P>0.05) . The CDE showing 4.78% (3.18%-8.88%) and EPT showing 14.05 s (10.07-20.85 s) in the laser group were significantly lower than the CDE showing 8.82% (6.01%-19.16%) and EPT showing 23.65 s (18.36-46.96 s) in the conventional group (z=2.30, 2.91; P<0.05) . The relative diameter and circularity in laser assisted capusulotomies were significantly more accurate (t=2.58, 3.92; P<0.05). The corneal endothelial cell loss showing 73.50 (-69.51-111.03)/mm(2) was significantly lower in the laser group than the loss of 118.06 (53.55 299.03)/mm(2) in the conventional group 1 month postoperatively (z=2.44; P<0.05). Postoperative anterial chamber flare was significantly greater in the conventional group at 1 day of 18.81 (13.32-20.23) ph/ms in laser group, 24.51(16.38-32.18)ph/m in conventional group and at 1 month of 13.01(9.23-16.28) ph/ms in laser group, 18.05(12.37-24.97) ph/ms in conventional group than the laser group (z=2.40, 2.31; P<0.05). There were no severe surgical complications for both groups. CONCLUSIONS: The femtosecond laser-assisted cataract surgery was effective and safe. It reduced EPT and CDE during operation, therefore decreased endothelial damage and postoperative anterior chamber inflammation. It also provided more precise and reproducible capsulotomies. PMID- 26906704 TI - [Evaluation of the safety and visual quality after implantation of the domestic made aspheric intraocular lens]. AB - OBJECTIVE: To evaluate the safety and efficacy of the domestic foldable one-piece aspheric intraocular lens (IOL, Model: A1-UV) for the treatment of cataract. METHODS: A prospective randomized controlled clinical research were conducted. One hundred and nineteen cases (119 eyes) of cataract patients were randomly assigned to the study group (58 cases) and the control group (61 cases). The study group were implanted with the domestic made aspheric intraocular lens (Model: A1-UV) and the control group were implanted with imported aspheric intraocular lens (Model: SN60WF, Alcon Laboratories, Inc.). The visual acuity and the slit lamp examination were evaluated 1-2 day, 1 week, 1 month, 3 months, 6 months and 1 year postoperatively. In addition, the contrast sensitivity tests were carried out 3 months, 6 months and 1 year postoperatively. Data were analyzed by chi-square test and independent t-test. RESULTS: 100 patients had completed 1 year of follow-up, among which 49 cases were from the study group and 51 cases were from the control group. No severe inflammation or complications associated with intraocular lens were noted in either group within 1 year follow up. The mean BCDVA, BCNVA, UCDVA, UCNVA(Log MAR) of the study group and the control group were 0.04+/-0.11, 0.11+/-0.17, 0.13+/-0.20, 0.35+/- 0.19 and 0.07+/ 0.15, 0.15+/-0.20, 0.18+/-0.23, 0.41+/-0.21 at 1 year postoperatively. No statistically significant differences were noted between groups in mean BCDVA, BCNVA, UCDVA, UCNVA (t=-1.39, P=0.166; t=- 1.25, P=0.216; t=-1.06, P=0.292; t= 1.59, P=0.116) at 1 year postoperatively. And there was no significant difference in visual acuity between the two groups (P>0.05) 1-2 day, 1 week, 1 month, 3 months and 6 months postoperatively. The difference of the contrast sensitivity between the two groups was not statistically significant (P>0.05), besides the contrast sensitivity of the study group was significantly better than the control group at 12c/d, 18 c/d under bright light(t=2.18, P=0.031; t=2.67, P=0.009) at 3 months postoperatively. And the mean contrast sensitivity of the study group and the control group at 12c/d, 18 c/d under bright light were 1.31 +/- 0.36, 0.86 +/ 0.41 and 1.15 +/- 0.40, 0.65 +/- 0.44 at 3 months postoperatively. CONCLUSION: The safety and efficacy of the domestic made foldable one-piece aspheric intraocular lens (Model: A1-UV) for the treatment of cataract is equivalent to the imported aspheric intraocular lens (Model: SN60WF). PMID- 26906705 TI - [The effect of phacoemulsification on intraocular pressure in eyes with primary angle closure glaucoma after trabeculectomy]. AB - OBJECTIVE: To evaluate the effect of phacoemulsification on intraocular pressure (IOP) in filtered eyes with primary angle closure glaucoma (PACG). METHODS: In this retrospective case series, 47 eyes from 47 PACG patients who previously had trabeculectomy were consecutively enrolled. All patients had visually significant cataracts and phacoemulsification was performed at least 3 months after trabeculectomy. The IOPs were recorded preoperatively, 1 day, 1 week, 2 weeks, 1 month, 3 months, 6 months, 12 months and 24 months after surgery. The best correct visual acuity (BCVA) , the number of glaucoma medications and the filtered bleb grade were recorded preoperatively and 24 months after phacoemulsification. IOP and BCVA before and after phacoemulsification were compared by student t test. The frequences of antiglaucoma medicine, bled grade and IOP control before and after phacoemulsification were compared by Mann Whitney Test. Linear regression analysis, Pearson and Spearman were performed to assess the correlation between IOP change and other variants. RESULTS: IOP was decreased significantly from (18.7+/-6.7) mmHg (1 mmHg=0.133 kPa) at baseline to 16.4+/-2.0 mmHg at final follow-up (t=2.54, P=0.015) . The median number of glaucoma medications was significantly decreased (P<0.01) at 2 years postoperatively. The magnitude of IOP reduction was significantly correlated with preoperative IOP (r=0.95, P<0.01). BCVA (LogMAR) was improved significantly at month 24 (t=5.62, P<0.01). Filtered bleb decreased insignificantly at 2 years postoperatively (P=0.113). Complete success, qualified success and failure rates in terms of IOP were 61.7%, 27.7% and 10.6% before surgery , 89.4%, 8.5%, 2.1% at 2 years postoperatively. In 29 patients with preoperative IOP<=21 mmHg, mean IOP increased insignificantly from (14.5+/-4.0) mmHg to (15.5 +/- 2.3) (P=0.195) at 2 years. In the 18 patients with preoperative IOP> 21 mmHg, mean IOP decreased from (25.3 +/- 4.4) mmHg preoperatively to (17.8 +/- 2.4) mmHg (P<0.01). CONCLUSIONS: Phacoemulsification reduces IOP and the number of glaucoma medications in previously filtered PACG eyes. The IOP remained normal in normal tension eyes after phacoemulsification in filtered PACG eyes but decreased significantly in hypertensive eyes. PMID- 26906706 TI - [The study of cyclosporin A modified intraocular lens preventing posterior capsular opacification in rabbit eyes]. AB - OBJECTIVE: To investigate the safety and efficacy of cyclosporine A sustained release from modified intraocular lens for preventing posterior capsular opacification (PCO) in rabbit eyes. METHODS: Forty-five New Zealand albino rabbits undergoing phacoemulsification in their right eyes were randomly and equally divided into three groups. Group A had implanted original IOL, group B had implanted PLGA-IOL(IOL coated with polylactide-glycoli acid), and group C had implanted CsA-PLGA-IOL (CsA loaded PLGA-IOL). All the 45 eyes were examined by a slit-lamp microscope. The intraocular pressures were recorded. Anterior chamber flare and aqueous humor cells were graded at different time point after surgery. The concentrations of CsA in the aqueous humor and blood were determined by high performance liquid chromatography. Anterior segment tissue was histologically examined. Wet posterior capsules were weighed. PCO was graded 6 months later. RESULTS: The mean concentrations of CsA in group C at 2 h,1 d,3 d,7 d,14 d,30 d,60 d after operation were (11.47+/-2.42) mg/L, (10.30+/-2.15) mg/L, (6.71+/ 1.45) mg/L, (4.81+/-1.16) mg/L, (6.11+/-0.84) mg/L, (2.53+/-0.77) mg/L, (0.86+/ 0.28) mg/L. The concentrations of CsA in blood were undetectable. During the early days after operation, the reactions of the anterior chamber in group A and B were more severe than group C. The initial appearance of PCO in group C was much later than in the other two groups, and the grade of PCO in group C was much lower than the other two groups. The mean weights of wet posterior capsules in group A(312.86+/-52.91) mg and B(310.64+/-62.42) mg were much heavier than that of group C(56.93 +/- 24.24) mg. Histological observation showed that there was remarkably less accumulation of lens materials on the posterior capsules in group C than in the other two groups. No toxic actions were found in intraocular tissues in group C. CONCLUSION: Our study suggested that Cyclosporin A modified intraocular lens could effectively and safely prevent the formation and development of posterior capsular opacification in rabbit eyes for a relatively long term. PMID- 26906707 TI - [A comparative study of lacrimal magnetic resonance hydrography and lacrimal endoscopy examination in the diagnosis and treatment of lacrimal duct obstructive diseases]. AB - OBJECTIVE: To evaluate the diagnostic value and treatment guidance of lacrimal magnetic resonance hydrography (LMRH) and lacrimal endoscopy examination in lacrimal duct obstruction. METHODS: A retrospective analysis of clinical and imaging data of 59 patients with epiphora who had LMRH examination in Tongji Hospital during June 2013 and January 2014. Multiplanar reconstruction (MPR) and maximum intensity projection (MIP) were used to process the three dimensions T2 weighted images (T2WI). The size of lacrimal sac, lacrimal mucosal lesions and the obstructed plane of nasolacrimal duct were observed. The lacrimal irrigation results were used as gold standard. The sensitivity, specificity, accuracy of LMRH in diagnosis of lacrimal duct obstructive diseases and the consistency between the two methods were analyzed. In addition, 22 cases had lacrimal endoscopy examination in less than half month after MRD. The results of lacrimal endoscopy were compared with LMRH images. The treatment method was made according to the results of LMRH and lacrimal endoscopy. RESULTS: According to the results of lacrimal irrigation, among 78 eyes of 59 patients, 2 eyes were diagnosed as lacrimal canalicular obstruction (2.6%, 2/78), 8 eyes were diagnosed as nasolacrimal duct stenosis (10.3%, 8/78), 24 eyes were diagnosed as nasolacrimal duct obstruction (30.8%, 24/78), 44 eyes were diagnosed as nasolacrimal duct obstruction accompanied with chronic dacryocystitis (56.4%, 44/78). The other 40 eyes were negative controls. LMRH had a high degree of consistency with lacrimal irrigation in diagnosis of lacrimal duct obstructive diseases. The value of Kappa was 0.963 (P= 0.026). The sensitivity of MRD in diagnosis of lacrimal duct obstructive diseases was 97.4%, the specificity was 100%, the accuracy was 98.3%, the positive predictive value was 100% and the negative predictive value was 95.2% . According to 40 eyes of the control group, the mean value of the maximum cross-sectional area of the lacrimal sac was: (10.9 +/- 0.4) mm(2). Twenty-two eyes underwent lacrimal endoscopy examination and the endoscopic findings were consistent with LMRH diagnosis. The lesions in the lacrimal duct displayed more clearly and intuitively than the LMRH, while LMRH had its unique advantages in showing the size of lacrimal sac, the mucosal thickness of lacrimal duct, large foreign bodies and lesions around the lacrimal duct. According to the results of LMRH and lacrimal endoscopy, 2 eyes of canalicular obstruction, 8 eyes of nasolacrimal duct stenosis, 20 eyes of nasolacrimal duct obstruction underwent lacrimal probing and stent implantation. Four eyes of nasolacrimal duct obstruction had drug treatment under lacrimal endoscopy. Thirty-eight eyes of chronic dacryocystitis underwent endonasal dacryocystorhinostomy. The other 6 eyes of chronic dacryocystitis underwent stent removal combined with endonasal dacryocystorhinostomy. CONCLUSIONS: LMRH is a noninvasive and reliable method to examine the lacrimal duct obstruction. It can better display the size of lacrimal sac, lacrimal mucosal thickness and surrounding soft tissues of lacrimal duct. It is also a good complementary method of lacrimal endoscopy and has guiding significance for individualized treatment in patients with lacrimal duct obstruction. PMID- 26906708 TI - [Comparison of balloon catheter dilatation and silicon intubation as the secondary treatment for congenital nasolacrimal duct obstruction after failed primary probing]. AB - OBJECTIVE: To determine the success rates and compare the results of balloon catheter dilation and nasolacrimal intubation as treatment for congenital nasolacrimal duct obstruction after failed probing, stratified by category of age and type of obstruction. METHODS: It was a prospective, randomized, clinical trial that enrolled 189 children (245 eyes) aged between 6 months to 48 months who had a history of failed nasolacrimal duct probing. All eyes underwent either balloon catheter nasolacrimal duct dilation or nasolacrimal duct intubation randomly. The eyes were divided into 2 age categories: category 1 (6-24 months) and category 2 (>24 months) and into 2 types of obstructions: simple obstruction and complex obstruction. Treatment success was defined as absence of epiphora, mucous discharge, or increased lacrimal lake at the outcome visit 6 months after surgery. Complications were also compared. RESULTS: In 124 eyes treated with balloon catheter dilatation, 112 were successful (90.3%) comparing with 106 successful eyes (87.6%) in 121 eyes treated with nasolacrimal duct intubation. The risk ratio for success between intubation and balloon dilation was 0.971, and the 95% confidence interval was 0.95-1.22. Within each age category, the success rate varied but did not show significant difference: In those under 24 months, success rate was 89.7% in 97 eyes treated with intubation, and 91.9% in 99 eyes treated with balloon dilation (RR, 0.976; 95% CI, 0.590-0.956). In those above 24 months, success rate was 79.1% in 24 eyes treated with intubation, and 84.0% in 25 eyes treated with balloon dilation (RR, 0.942; 95%CI, 0.813-1.387). In the group of simple obstruction, success rate was 96.5% in 87 eyes treated with intubation, and 93.1% in 88 eyes treated with balloon dilation (RR, 1.036; 95% CI, 0.967-1.105). In the group of complex obstruction, Success rate was 64.7% in 34 eyes treated with intubation, and 86.1% in 36 eyes treated with balloon dilation. The success rate of balloon dilatation showed slightly higher than that of intubation (RR, 0.751; 95% CI, 0.590-0.956). There were 59 eyes showed complications in intubation group, while only 2 eyes in balloon dilation group. CONCLUSIONS: Both balloon catheter dilation and nasolacrimal duct intubation could alleviate the clinical signs of persistent nasolacrimal duct obstruction with a similar percentage of patients. In the complex obstruction group, balloon catheter dilation showed better efficacy than nasolacrimal duct intubation. PMID- 26906709 TI - [Research progress in relative crystallin genes of congenital cataract]. AB - Congenital cataract is the common cause of visual disability in children. Nearly one third of congenital cataract cases may have a related genetic mutation. With the development of molecular genetics, especially gentechnik, more and more genes, such as crystallin genes, membrane protein genes, eytoskeletal protein genes and regulatory protein genes have been confirmed to participate in the process of congenital cataract. Furthermore, crystallin genes account for most of these genes and the crystallin has the highest amount of the whole protein in lens.It has been found that nearly one hundred mutations in crystallin genes are associated with the onset of congenital cataract. Researchers are exploring how these mutations further affect the function of cellular biology and eventually lead to cataract. Although more and more research results gradually reveal the pathogenesis of congenital cataract from the level of gene and protein, the specific pathogenesis is still unclear. The recent progression about inherited congenital cataract related with crysallin genes is summarized in this review. PMID- 26906710 TI - [Ocular immune reconstitution inflammatory syndrome]. AB - Immune reconstitution inflammatory syndrome (IRIS) is a collection of inflammatory disorders associated with paradoxical worsening of preexisting infectious processes or emerging diseases or even dead after the initiation of highly active antiretroviral therapy (HAART) in human immunodeficiency virus (HIV) infected individuals in a period of recovery of immune function. Ocular immune reconstitution inflammatory syndrome is mainly caused by cytomegalovirus which performing a series of ocular inflammation accompanied with the increase of CD4+ T lymphocytes, such as cytomegalovirus retinitis, after HAART. With HAART widely used, the patients of IRIS gradually increased. But the clinical presentations of IRIS were various because of different pathogens. This review summarized the clinical manifestations, risk factors, diagnosis and treatment of ocular IRIS. PMID- 26906711 TI - The use of biochemical markers of bone turnover in the clinical management of primary and secondary osteoporosis. AB - The purpose of the present study was to examine of the current role of bone turnover markers (BTMs) in the management of osteoporosis. Perusal of the literature examines the available evidence for the utility of BTMs for decision to treat and for the monitoring of treatment for osteoporosis. There is no evidence for the use of BTMs for fracture risk calculation, decision to treat or for treatment selection. A very abnormal BTM value may be a clue to the presence of bone pathology other than uncomplicated osteoporosis. Whilst changes to BTMs following various osteoporosis treatments are well defined, their utility in monitoring individual patients has been less well established. Some fracture outcome-based data exist for the use of u-NTX target of <21 nmol BCE/mmol for antiresorptive therapy; the equivalent s-CTX level is ~250 ng/L. Suboptimal BTM response to treatment may indicate non-compliance or the presence of secondary causes of osteoporosis which may need addressing. Studies are needed to establish treatment targets based on fracture outcomes for commonly used BTMs for each established osteoporosis therapy. PMID- 26906712 TI - Dipeptidyl peptidase-4 activity might be a link between tumour necrosis factor alpha and insulin resistance in type 1 diabetes. AB - Tumour necrosis factor alpha (TNF alpha) leads to beta cell damage in type 1 diabetes (T1DM) but also causes insulin resistance (IR). It modulates dipeptidyl peptidase-4 (DPP-4) activity, adipokine linked with both IR and T1DM. We were interested if there is an association of TNF alpha in conjunction with DPP-4 and IR in T1DM. DPP-4 activity, TNF alpha concentration measurements, and insulin sensitivity calculation using estimated glucose disposal rate (eGDR) equation were performed in 70 T1DM patients. They were divided into two groups according to eGDR median. The group with higher IR had higher value of DPP-4 activity (27.57 +/- 1.77 vs. 18.33 +/- 1.14, p < 0.001) and TNF alpha concentration (12.91 +/- 0.83 vs. 6.72 +/- 0.36, p < 0.001). TNF alpha concentration and DPP-4 activity negatively correlated with eGDR (r = -0.616, p < 0.001 and r = -0.643, p < 0.001) while correlating positively with each other (r = 0.422; p = 0.001). The linear regression showed that eGDR decreases for 0.166 mg kg(-1) min(-1) by TNF alpha concentration increase of 1 pg/mL (p < 0.001) and for 0.090 mg kg(-1) min( 1) by DPP-4 activity increase of 1 U/L (p = 0.001) when adjusted for age, gender disease duration, glycated haemoglobin, body mass index and waist-to-hip ratio. eGDR decreased by additional 0.60 mg kg(-1) min(-1) (B = -0.150, p < 0.001) when DPP-4 activity was additionally adjusted for TNF alpha. TNF alpha concentration is associated with IR, correlates with its severity and increases the drop in insulin sensitivity modulated by DPP-4 activity. Whether TNF alpha involvement in the insulin signalling pathway is mediated by DPP-4 activity needs to be further evaluated. PMID- 26906714 TI - Transfer-Free Growth of Atomically Thin Transition Metal Disulfides Using a Solution Precursor by a Laser Irradiation Process and Their Application in Low Power Photodetectors. AB - Although chemical vapor deposition is the most common method to synthesize transition metal dichalcogenides (TMDs), several obstacles, such as the high annealing temperature restricting the substrates used in the process and the required transfer causing the formation of wrinkles and defects, must be resolved. Here, we present a novel method to grow patternable two-dimensional (2D) transition metal disulfides (MS2) directly underneath a protective coating layer by spin-coating a liquid chalcogen precursor onto the transition metal oxide layer, followed by a laser irradiation annealing process. Two metal sulfides, molybdenum disulfide (MoS2) and tungsten disulfide (WS2), are investigated in this work. Material characterization reveals the diffusion of sulfur into the oxide layer prior to the formation of the MS2. By controlling the sulfur diffusion, we are able to synthesize continuous MS2 layers beneath the top oxide layer, creating a protective coating layer for the newly formed TMD. Air stable and low-power photosensing devices fabricated on the synthesized 2D WS2 without the need for a further transfer process demonstrate the potential applicability of TMDs generated via a laser irradiation process. PMID- 26906713 TI - Effect of pasireotide on glucose- and growth hormone-related biomarkers in patients with inadequately controlled acromegaly. AB - The purpose of this study was to gain more insight into the mechanism of action of pasireotide in patients who completed the PAOLA study. PAOLA was a 24-week, Phase III, randomized, three-arm study of pasireotide LAR 40 and 60 mg versus octreotide LAR 30 mg or lanreotide Autogel 120 mg in patients with inadequately controlled acromegaly. The current work was a planned exploratory objective of the PAOLA study that evaluated changes in levels of growth hormone (GH), insulin like growth factor 1 (IGF-1), IGF-binding proteins (IGFBP-2, IGFBP-3), glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG) in each treatment arm. Responders to pasireotide LAR (mean GH levels <2.5 MUg/L and normal IGF-1 levels at 24 weeks) had lower GH and IGF-1 levels at baseline (GH 5.1 ng/mL, IGF-1 519 ng/mL) than non-responders (GH 7.9 ng/mL, IGF-1 672 ng/mL). Frequency of hyperglycaemia after pasireotide treatment was similar in responders and non responders and depended more on the baseline FPG level. 47 % of all patients treated with pasireotide LAR (40 or 60 mg) did not receive antidiabetic medication at any time during this study. This is the first study to evaluate the treatment effect of pasireotide on key hormonal and glycaemic biomarkers and to identify potential predictors of pasireotide-associated hyperglycaemia. Pre treatment glucose status may be predictive of the development of pasireotide associated hyperglycaemia. A large subset of patients with acromegaly does not experience major disturbances in glucose homeostasis while receiving pasireotide LAR. PMID- 26906717 TI - Percutaneous treatment of parastomal varices: Direct or transhepatic approach? PMID- 26906718 TI - Structural insights into the Aedes aegypti aquaporins and aquaglyceroporins - an in silico study. AB - There has been a fair bit of understanding on the structure-function relationship of Aquaporins (AQPs) from plants and vertebrates obtained from available X-ray crystallography data. However, there is a lacuna in understanding the structure of AQPs from sanguinivorous insects like the mosquito where it plays a crucial role in survival. In this study, we have built homology models for the Aedes aegypti AQPs, identified key channel lining residues and compared the structure and sequence with orthodox AQPs. Although Ar/R filter residues of AaAQP1 were exactly similar to orthodox AQPs, AaAQP2 has a substitution at LE1position possibly making it less efficient in high capacity water transport. The huge difference in the selectivity filter region of AaAQP3 suggests a different transport property for this channel. The changes observed in the H5 position of the filter of AaAQP4 and AaAQP5 may explain the presence of a larger pore aperture to permit the passage of larger solute molecules. AaAQP6 possesses a completely hydrophobic filter like that in mammalian super aquaporins. The identified key residues are pivotal in understanding the mechanism of action and gating of these channels. PMID- 26906716 TI - Disorganization of white matter architecture in major depressive disorder: a meta analysis of diffusion tensor imaging with tract-based spatial statistics. AB - White matter (WM) abnormalities have long been suspected in major depressive disorder (MDD). Tract-based spatial statistics (TBSS) studies have detected abnormalities in fractional anisotropy (FA) in MDD, but the available evidence has been inconsistent. We performed a quantitative meta-analysis of TBSS studies contrasting MDD patients with healthy control subjects (HCS). A total of 17 studies with 18 datasets that included 641 MDD patients and 581 HCS were identified. Anisotropic effect size-signed differential mapping (AES-SDM) meta analysis was performed to assess FA alterations in MDD patients compared to HCS. FA reductions were identified in the genu of the corpus callosum (CC) extending to the body of the CC and left anterior limb of the internal capsule (ALIC) in MDD patients relative to HCS. Descriptive analysis of quartiles, sensitivity analysis and subgroup analysis further confirmed these findings. Meta-regression analysis revealed that individuals with more severe MDD were significantly more likely to have FA reductions in the genu of the CC. This study provides a thorough profile of WM abnormalities in MDD and evidence that interhemispheric connections and frontal-striatal-thalamic pathways are the most convergent circuits affected in MDD. PMID- 26906715 TI - IK-guided PP2A suppresses Aurora B activity in the interphase of tumor cells. AB - Aurora B activation is triggered at the mitotic entry and required for proper microtubule-kinetochore attachment at mitotic phase. Therefore, Aurora B should be in inactive form in interphase to prevent aberrant cell cycle progression. However, it is unclear how the inactivation of Aurora B is sustained during interphase. In this study, we find that IK depletion-induced mitotic arrest leads to G2 arrest by Aurora B inhibition, indicating that IK depletion enhances Aurora B activation before mitotic entry. IK binds to Aurora B, and colocalizes on the nuclear foci during interphase. Our data further show that IK inhibits Aurora B activation through recruiting PP2A into IK and Aurora B complex. It is thus believed that IK, as a scaffold protein, guides PP2A into Aurora B to suppress its activity in interphase until mitotic entry. PMID- 26906719 TI - Chinese medicine syndromes in congestive heart failure: A literature study and retrospective analysis of clinical cases. AB - OBJECTIVE: To discuss the characteristics of Chinese medicine (CM) syndrome factors and distribution of congestive heart failure (CHF), and provide a basis for the diagnosis criteria of essential syndromes. METHODS: Based on databases of China National Knowledge Infrastructure (CNKI, 1980-2012) and Chinese Journal of Chongqing VIP Database (1989-2012), the eligible studies in CHF and extracted factors associated with compound syndromes were analyzed. All the syndromes were classified into deficiency, excess, and deficiency-excess in complexity syndrome were classified. Compound syndromes were separated into syndrome factors including single, double, three or four factors, along with the frequency of occurrence. The relation of CHF syndromes with age, gender, primary disease, brain natriuretic peptide (BNP) and cardiac functional grade was studied in 1,451 CHF cases (between December 2010 and September 2012), and the clinical distribution of common CHF syndromes was summarized. RESULTS: The literature study involved 6,799 CHF cases in 66 literatures after screening. Of the different factors affecting CHF, qi deficiency was the most important one. In deficiency syndrome, Xin (Heart)-qi-deficiency was the most common single factor, and deficiency of both qi and yin was the most common double factor. The retrospective analysis involved 1,451 CHF cases (431 cases with test results of BNP). The xin blood stasis and obstruction and deficiency of both qi and yin syndrome were mostly seen in female patients, and phlegm-blocking-Xin-vessel and qi-deficiency-blood-stasis syndrome mostly in males. Xin-qi-deficiency and qi deficiency-blood-stasis syndrome were mostly seen in patients aged 50-60 years. Patients aged over 60 years likely manifest deficiency of both qi and yin and Xin blood stasis and obstruction syndrome. The severity of syndrome is aggravated with increased BNP and cardiac functional grade. CONCLUSIONS: The essential syndromes of CHF include qi-deficiency-blood-stasis and deficiency of both qi and yin. The clinical distribution is linked to patients' age and gender. BNP and cardiac functional grade is closely related to CHF syndromes, which may indicate the severity of CM syndromes of CHF. PMID- 26906721 TI - Deterioration of dyslexia after non-dominant temporal lobectomy for drug resistant epilepsy. AB - We present a patient with drug-resistant right-sided temporal lobe epilepsy, caused by a ganglioglioma of the parahippocampal gyrus. Preoperatively, the patient was also known to have dyslexia. A right-sided anterior temporal lobectomy, including complete lesionectomy, was performed. Several months after the otherwise uncomplicated procedure, the patient complained about visual memory disturbances, accompanied by increased reading and spelling problems. Postoperative neuropsychological examination revealed deterioration of the visual memory functions, compared to the preoperative assessment, and consequently provided a possible explanation for worsening of the pre-existing dyslexia. In this case report, we hypothesize on the cause of this unusual deterioration and present recommendations to be included in the preoperative epilepsy surgery evaluation for patients with verbal or reading disorders such as dyslexia. PMID- 26906722 TI - [Bilateral villonodular synovitis of the knee joint in a diabetic patient]. PMID- 26906723 TI - Prevalence of hyperuricemia among Beijing post-menopausal women in 10 years. AB - OBJECTIVES: The objective of this study was to explore the trend and risk factors of the prevalence of hyperuricemia among post-menopausal women in Beijing over a ten years period. METHOD: This research was based on two cross-sectional surveys in post-menopausal women in Beijing. A total of 1881 post-menopausal women were included. Subjects answered a questionnaire and underwent a physical examination and blood test. Serum uric acid >357 MUmol/L was diagnosed as hyperuricemia, and another diagnosis criterion (serum uric acid >416 MUmol/L) was applied in these women. RESULTS: Serum uric acid levels and hyperuricemia prevalence increased remarkably in the 10-year period. The prevalence of hyperuricemia increased more than 2-fold after being adjusted by age. Multivariate logistic regression models revealed hyperuricemia associated with age, education level, urban residents, alcohol consumption, hypertension, obesity, and dyslipidemia. With the increasing number of traditional cardiovascular risk factors (including hypertension, obesity, diabetes, and dyslipidemia), the risk of hyperuricemia increased significantly, and the accumulative effect of the factors on the risk of hyperuricemia was determined. CONCLUSION: The prevalence of hyperuricemia was high and exhibited a remarkable, increasing trend in Beijing community-based, post-menopausal women. Better management of relative factors could help to prevent further increases in the burden of hyperuricemia in post-menopausal women in this region. PMID- 26906724 TI - Mild and Site-Selective Allylation of Enol Carbamates with Allylic Carbonates under Rhodium Catalysis. AB - The rhodium(III)-catalyzed mild and site-selective C-H allylation of enol carbamates with 4-vinyl-1,3-dioxolan-2-one and allylic carbonates affords allylic alcohols and terminal allylated products, respectively. The assistance of the carbamoyl directing group provides a straightforward preparation of biologically and synthetically important allylated enol carbamates. PMID- 26906720 TI - Tissue-resident dendritic cells and diseases involving dendritic cell malfunction. AB - Dendritic cells (DCs) control immune responses and are central to the development of immune memory and tolerance. DCs initiate and orchestrate immune responses in a manner that depends on signals they receive from microbes and cellular environment. Although DCs consist mainly of bone marrow-derived and resident populations, a third tissue-derived population resides the spleen and lymph nodes (LNs), different subsets of tissue-derived DCs have been identified in the blood, spleen, lymph nodes, skin, lung, liver, gut and kidney to maintain the tolerance and control immune responses. Tissue-resident DCs express different receptors for microbe-associated molecular patterns (MAMPs) and damage-associated molecular patterns (DAMPs), which were activated to promote the production of pro- or anti inflammatory cytokines. Malfunction of DCs contributes to diseases such as autoimmunity, allergy, and cancer. It is therefore important to update the knowledge about resident DC subsets and diseases associated with DC malfunction. PMID- 26906726 TI - [Student Program Success Story: Review of the DGRh Congress 2015]. PMID- 26906725 TI - Neuroprotective Effects of A Standardized Flavonoid Extract of Safflower Against Neurotoxin-Induced Cellular and Animal Models of Parkinson's Disease. AB - Safflower has long been used to treat cerebrovascular diseases in China. We previously reported that kaempferol derivatives of safflower can bind DJ-1, a protein associated with Parkinson's disease (PD), and flavonoid extract of safflower exhibited neuroprotective effects in a 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced mouse model of PD. In this study, a standardized safflower flavonoid extract (SAFE) was isolated from safflower and mainly contained flavonoids. Two marker compounds of SAFE, kaempferol 3-O-rutinoside and anhydrosafflor yellow B, were proven to suppress microtubule destabilization and decreased cell area, respectively. We confirmed that SAFE in dripping pill form could improve behavioural performances in a 6-hydroxydopamine (6-OHDA)-induced rat model of PD, partially via the suppression of alpha-synuclein overexpression or aggregation, as well as the suppression of reactive astrogliosis. Using an MRI tracer-based method, we found that 6-OHDA could change extracellular space (ECS) diffusion parameters, including a decrease in tortuosity and the rate constant of clearance and an increase in the elimination half-life of the tracer in the 6 OHDA-lesioned substantia nigra. SAFE treatment could partially inhibit the changes in ECS diffusion parameters, which might provide some information about neuronal loss and astrocyte activation. Consequently, our results indicate that SAFE is a potential therapeutic herbal product for treatment of PD. PMID- 26906728 TI - Plant Cell Shape: Trafficking Gets Edgy. AB - Polyhedral-shaped plant cells have faces, corners, and edges that can have different material properties. As Kirchhelle et al. (2016) now show, RAB-A5c reveals a trafficking compartment that localizes to the edges where two cell walls meet, with a potential role in mediating local wall stiffness. PMID- 26906727 TI - Measuring kinetic drivers of pneumolysin pore structure. AB - Most membrane attack complex-perforin/cholesterol-dependent cytolysin (MACPF/CDC) proteins are thought to form pores in target membranes by assembling into pre pore oligomers before undergoing a pre-pore to pore transition. Assembly during pore formation is into both full rings of subunits and incomplete rings (arcs). The balance between arcs and full rings is determined by a mechanism dependent on protein concentration in which arc pores arise due to kinetic trapping of the pre pore forms by the depletion of free protein subunits during oligomerization. Here we describe the use of a kinetic assay to study pore formation in red blood cells by the MACPF/CDC pneumolysin from Streptococcus pneumoniae. We show that cell lysis displays two kinds of dependence on protein concentration. At lower concentrations, it is dependent on the pre-pore to pore transition of arc oligomers, which we show to be a cooperative process. At higher concentrations, it is dependent on the amount of pneumolysin bound to the membrane and reflects the affinity of the protein for its receptor, cholesterol. A lag occurs before cell lysis begins; this is dependent on oligomerization of pneumolysin. Kinetic dissection of cell lysis by pneumolysin demonstrates the capacity of MACPF/CDCs to generate pore-forming oligomeric structures of variable size with, most likely, different functional roles in biology. PMID- 26906729 TI - A GPCR Handles Bacterial Sensing in Chemotaxis and Phagocytosis. AB - In this issue of Developmental Cell, Pan et al. (2016) identified in cells of the social amoeba Dictyostelium a G protein-coupled receptor (GPCR) that recognizes a chemoattractant secreted by bacteria. This work uncovers a mechanism by which a single GPCR mediates pseudopod extension during cell migration and bacterial engulfment. PMID- 26906730 TI - Painting a Clearer Picture of Chromatin. AB - Elucidating chromatin's 3D shape is critical to understanding its function, but the fine structure of chromatin domains remains poorly resolved. In a recent report in Nature, Boettiger et al. (2016) visualize chromatin in super resolution, gaining unprecedented insight into chromatin architecture. PMID- 26906731 TI - Making Waves toward the Shore by Synchronicity. AB - A study by Tsiairis and Aulehla (2016), published in Cell, reveals that randomized mixtures of dissociated presomitic mesoderm (PSM) cells reestablish wave-like propagating patterns of oscillatory gene expression by tuning the oscillation dynamics in response to surrounding cells. Thus, PSM cells self organize the phase-coupled oscillators. PMID- 26906732 TI - Kar9 Controls the Cytoplasm by Visiting the Nucleus. AB - Kar9 positions mitotic spindles during budding yeast cell division. Reporting in this issue of Developmental Cell, Schweiggert et al. (2016) show that modulation of Kar9 stability mediates crosstalk between cytoplasmic and nuclear microtubules, using an elaborate mechanism that involves regulated nuclear transport as well as SUMOylation and ubiquitination. PMID- 26906733 TI - Mechanisms of Cardiac Regeneration. AB - Adult humans fail to regenerate their hearts following injury, and this failure to regenerate myocardium is a leading cause of heart failure and death worldwide. Although all adult mammals appear to lack significant cardiac regeneration potential, some vertebrates can regenerate myocardium throughout life. In addition, new studies indicate that mammals have cardiac regeneration potential during development and very soon after birth. The mechanisms of heart regeneration among model organisms, including neonatal mice, appear remarkably similar. Orchestrated waves of inflammation, matrix deposition and remodeling, and cardiomyocyte proliferation are commonly seen in heart regeneration models. Understanding why adult mammals develop extensive scarring instead of regeneration is a crucial goal for regenerative biology. PMID- 26906734 TI - Distinct Activities of Myf5 and MyoD Indicate Separate Roles in Skeletal Muscle Lineage Specification and Differentiation. AB - Most transcription factor families contain highly related paralogs generated by gene duplication, and functional divergence is generally accomplished by activation of distinct sets of genes by each member. Here we compare the molecular functions of Myf5 and MyoD, two highly related bHLH transcription factors that regulate skeletal muscle specification and differentiation. We find that MyoD and Myf5 bind the same sites genome-wide but have distinct functions: Myf5 induces histone acetylation without Pol II recruitment or robust gene activation, whereas MyoD induces histone acetylation, recruits Pol II, and robustly activates gene transcription. Therefore, the initial specification of the muscle lineage by Myf5 occurs without significant induction of gene transcription. Transcription of the skeletal muscle program is then achieved by the subsequent expression of MyoD, which binds to the same sites as Myf5, indicating that each factor regulates distinct steps in gene initiation and transcription at a shared set of binding sites. PMID- 26906736 TI - A WntD-Dependent Integral Feedback Loop Attenuates Variability in Drosophila Toll Signaling. AB - Patterning by morphogen gradients relies on the capacity to generate reproducible distribution profiles. Morphogen spread depends on kinetic parameters, including diffusion and degradation rates, which vary between embryos, raising the question of how variability is controlled. We examined this in the context of Toll dependent dorsoventral (DV) patterning of the Drosophila embryo. We find that low embryo-to-embryo variability in DV patterning relies on wntD, a Toll-target gene expressed initially at the posterior pole. WntD protein is secreted and disperses in the extracellular milieu, associates with its receptor Frizzled4, and inhibits the Toll pathway by blocking the Toll extracellular domain. Mathematical modeling predicts that WntD accumulates until the Toll gradient narrows to its desired spread, and we support this feedback experimentally. This circuit exemplifies a broadly applicable induction-contraction mechanism, which reduces patterning variability through a restricted morphogen-dependent expression of a secreted diffusible inhibitor. PMID- 26906735 TI - The Specification of Geometric Edges by a Plant Rab GTPase Is an Essential Cell Patterning Principle During Organogenesis in Arabidopsis. AB - Plant organogenesis requires control over division planes and anisotropic cell wall growth, which each require spatial patterning of cells. Polyhedral plant cells can display complex patterning in which individual faces are established as biochemically distinct domains by endomembrane trafficking. We now show that, during organogenesis, the Arabidopsis endomembrane system specifies an important additional cellular spatial domain: the geometric edges. Previously unidentified membrane vesicles lying immediately beneath the plasma membrane at cell edges were revealed through localization of RAB-A5c, a plant GTPase of the Rab family of membrane-trafficking regulators. Specific inhibition of RAB-A5c activity grossly perturbed cell geometry in developing lateral organs by interfering independently with growth anisotropy and cytokinesis without disrupting default membrane trafficking. The initial loss of normal cell geometry can be explained by a failure to maintain wall stiffness specifically at geometric edges. RAB-A5c thus meets a requirement to specify this cellular spatial domain during organogenesis. PMID- 26906737 TI - Regulation of a Spindle Positioning Factor at Kinetochores by SUMO-Targeted Ubiquitin Ligases. AB - Correct function of the mitotic spindle requires balanced interplay of kinetochore and astral microtubules that mediate chromosome segregation and spindle positioning, respectively. Errors therein can cause severe defects ranging from aneuploidy to developmental disorders. Here, we describe a protein degradation pathway that functionally links astral microtubules to kinetochores via regulation of a microtubule-associated factor. We show that the yeast spindle positioning protein Kar9 localizes not only to astral but also to kinetochore microtubules, where it becomes targeted for proteasomal degradation by the SUMO targeted ubiquitin ligases (STUbLs) Slx5-Slx8. Intriguingly, this process does not depend on preceding sumoylation of Kar9 but rather requires SUMO-dependent recruitment of STUbLs to kinetochores. Failure to degrade Kar9 leads to defects in both chromosome segregation and spindle positioning. We propose that kinetochores serve as platforms to recruit STUbLs in a SUMO-dependent manner in order to ensure correct spindle function by regulating levels of microtubule associated proteins. PMID- 26906738 TI - Identification of a Chemoattractant G-Protein-Coupled Receptor for Folic Acid that Controls Both Chemotaxis and Phagocytosis. AB - Eukaryotic phagocytes search and destroy invading microorganisms via chemotaxis and phagocytosis. The social amoeba Dictyostelium discoideum is a professional phagocyte that chases bacteria through chemotaxis and engulfs them as food via phagocytosis. G-protein-coupled receptors (GPCRs) are known for detecting chemoattractants and directing cell migration, but their roles in phagocytosis are not clear. Here, we developed a quantitative phosphoproteomic technique to discover signaling components. Using this approach, we discovered the long sought after folic acid receptor, fAR1, in D. discoideum. We showed that the seven transmembrane receptor fAR1 is required for folic acid-mediated signaling events. Significantly, we discovered that fAR1 is essential for both chemotaxis and phagocytosis of bacteria, thereby representing a chemoattractant GPCR that mediates not only chasing but also ingesting bacteria. We revealed that a phagocyte is able to internalize particles via a chemoattractant-mediated engulfment process. We propose that mammalian phagocytes may also use this mechanism to engulf and ingest bacterial pathogens. PMID- 26906739 TI - Regulation of Golgi Cisternal Progression by Ypt/Rab GTPases. AB - Current models entail that transport through the Golgi-the main sorting compartment of the cell-occurs via cisternal progression/maturation and that Ypt/Rab GTPases regulate this process. However, there is very limited evidence that cisternal progression is regulated, and no evidence for involvement of Ypt/Rab GTPases in such a regulation. Moreover, controversy about the placement of two of the founding members of the Ypt/Rab family, Ypt1 and Ypt31, to specific Golgi cisternae interferes with addressing this question in yeast, where cisternal progression has been extensively studied. Here, we establish the localization of Ypt1 and Ypt31 to opposite faces of the Golgi: early and late, respectively. Moreover, we show that they partially overlap on a transitional compartment. Finally, we determine that changes in Ypt1 and Ypt31 activity affect Golgi cisternal progression, early-to-transitional and transitional-to-late, respectively. These results show that Ypt/Rab GTPases regulate two separate steps of Golgi cisternal progression. PMID- 26906740 TI - Architecture and Characteristics of Bacterial Nanotubes. AB - Bacteria display an array of contact-dependent interaction systems that have evolved to facilitate direct cell-to-cell communication. We have previously identified a mode of bacterial communication mediated by nanotubes bridging neighboring cells. Here, we elucidate nanotube architecture, dynamics, and molecular components. Utilizing Bacillus subtilis as a model organism, we found that at low cell density, nanotubes exhibit remarkable complexity, existing as both intercellular tubes and extending tubes, with the latter frequently surrounding the cells in a "root-like" fashion. Observing nanotube formation in real time showed that these structures are formed in the course of minutes, displaying rapid movements. Utilizing a combination of super-resolution, light, and electron microscopy, we revealed that nanotubes are composed of chains of membranous segments harboring a continuous lumen. Furthermore, we discovered that a conserved calcineurin-like protein, YmdB, presents in nanotubes and is required for both nanotube production and intercellular molecular trade. PMID- 26906742 TI - Effects of stage of pregnancy on variance components, daily milk yields and 305 day milk yield in Holstein cows, as estimated by using a test-day model. AB - Pregnancy and calving are elements indispensable for dairy production, but the daily milk yield of cows decline as pregnancy progresses, especially during the late stages. Therefore, the effect of stage of pregnancy on daily milk yield must be clarified to accurately estimate the breeding values and lifetime productivity of cows. To improve the genetic evaluation model for daily milk yield and determine the effect of the timing of pregnancy on productivity, we used a test day model to assess the effects of stage of pregnancy on variance component estimates, daily milk yields and 305-day milk yield during the first three lactations of Holstein cows. Data were 10 646 333 test-day records for the first lactation; 8 222 661 records for the second; and 5 513 039 records for the third. The data were analyzed within each lactation by using three single-trait random regression animal models: one model that did not account for the stage of pregnancy effect and two models that did. The effect of stage of pregnancy on test-day milk yield was included in the model by applying a regression on days pregnant or fitting a separate lactation curve for each days open (days from calving to pregnancy) class (eight levels). Stage of pregnancy did not affect the heritability estimates of daily milk yield, although the additive genetic and permanent environmental variances in late lactation were decreased by accounting for the stage of pregnancy effect. The effects of days pregnant on daily milk yield during late lactation were larger in the second and third lactations than in the first lactation. The rates of reduction of the 305-day milk yield of cows that conceived fewer than 90 days after the second or third calving were significantly (P<0.05) greater than that after the first calving. Therefore, we conclude that differences between the negative effects of early pregnancy in the first, compared with later, lactations should be included when determining the optimal number of days open to maximize lifetime productivity in dairy cows. PMID- 26906741 TI - Quantitative Multiscale Cell Imaging in Controlled 3D Microenvironments. AB - The microenvironment determines cell behavior, but the underlying molecular mechanisms are poorly understood because quantitative studies of cell signaling and behavior have been challenging due to insufficient spatial and/or temporal resolution and limitations on microenvironmental control. Here we introduce microenvironmental selective plane illumination microscopy (meSPIM) for imaging and quantification of intracellular signaling and submicrometer cellular structures as well as large-scale cell morphological and environmental features. We demonstrate the utility of this approach by showing that the mechanical properties of the microenvironment regulate the transition of melanoma cells from actin-driven protrusion to blebbing, and we present tools to quantify how cells manipulate individual collagen fibers. We leverage the nearly isotropic resolution of meSPIM to quantify the local concentration of actin and phosphatidylinositol 3-kinase signaling on the surfaces of cells deep within 3D collagen matrices and track the many small membrane protrusions that appear in these more physiologically relevant environments. PMID- 26906743 TI - The first decade of estrogen receptor cistromics in breast cancer. AB - The advent of genome-wide transcription factor profiling has revolutionized the field of breast cancer research. Estrogen receptor alpha (ERalpha), the major drug target in hormone receptor-positive breast cancer, has been known as a key transcriptional regulator in tumor progression for over 30 years. Even though this function of ERalpha is heavily exploited and widely accepted as an Achilles heel for hormonal breast cancer, only since the last decade we have been able to understand how this transcription factor is functioning on a genome-wide scale. Initial ChIP-on-chip (chromatin immunoprecipitation coupled with tiling array) analyses have taught us that ERalpha is an enhancer-associated factor binding to many thousands of sites throughout the human genome and revealed the identity of a number of directly interacting transcription factors that are essential for ERalpha action. More recently, with the development of massive parallel sequencing technologies and refinements thereof in sample processing, a genome wide interrogation of ERalpha has become feasible and affordable with unprecedented data quality and richness. These studies have revealed numerous additional biological insights into ERalpha behavior in cell lines and especially in clinical specimens. Therefore, what have we actually learned during this first decade of cistromics in breast cancer and where may future developments in the field take us? PMID- 26906744 TI - Vitamin D deficiency impairs skeletal muscle function in a smoking mouse model. AB - Chronic obstructive pulmonary disease (COPD) is associated with skeletal muscle dysfunction. Vitamin D plays an important role in muscle strength and performance in healthy individuals. Vitamin D deficiency is highly prevalent in COPD, but its role in skeletal muscle dysfunction remains unclear. We examined the time-course effect of vitamin D deficiency on limb muscle function in mice with normal or deficient vitamin D serum levels exposed to air or cigarette smoke for 6, 12 or 18 weeks. The synergy of smoking and vitamin D deficiency increased lung inflammation and lung compliance from 6 weeks on with highest emphysema scores observed at 18 weeks. Smoking reduced body and muscle mass of the soleus and extensor digitorum longus (EDL), but did not affect contractility, despite type II atrophy. Vitamin D deficiency did not alter muscle mass but reduced muscle force over time, downregulated vitamin D receptor expression, and increased muscle lipid peroxidation but did not alter actin and myosin expression, fiber dimensions or twitch relaxation time. The combined effect of smoking and vitamin D deficiency did not further deteriorate muscle function but worsened soleus mass loss and EDL fiber atrophy at 18 weeks. We conclude that the synergy of smoking and vitamin D deficiency in contrast to its effect on lung disease, had different, independent but important noxious effects on skeletal muscles in a mouse model of mild COPD. PMID- 26906745 TI - Palmitoylated PrRP analog decreases body weight in DIO rats but not in ZDF rats. AB - Anorexigenic neuropeptides produced and acting in the brain have the potential to decrease food intake and ameliorate obesity, but are ineffective after peripheral application, owing to a limited ability to cross the blood-brain barrier. We have designed lipidized analogs of prolactin-releasing peptide (PrRP), which is involved in energy balance regulation as demonstrated by obesity phenotypes of both Prrp-knockout and Prrp receptor-knockout mice. The aim of this study was to characterize the subchronic effect of a palmitoylated PrRP analog in two rat models of obesity and diabetes: diet-induced obese Sprague-Dawley rats and leptin receptor-deficient Zucker diabetic (ZDF) rats. In the rats with diet-induced obesity (DIO), a two-week intraperitoneal treatment with palmitoylated PrRP lowered food intake by 24% and body weight by 8%. This treatment also improved glucose tolerance and tended to decrease leptin levels and adipose tissue masses in a dose-dependent manner. In contrast, in ZDF rats, the same treatment with palmitoylated PrRP lowered food intake but did not significantly affect body weight or glucose tolerance, probably in consequence of severe leptin resistance due to a nonfunctional leptin receptor. Our data indicate a good efficacy of lipidized PrRP in DIO rats. Thus, the strong anorexigenic, body weight-reducing, and glucose tolerance-improving effects make palmitoylated PrRP an attractive candidate for anti-obesity treatment. PMID- 26906746 TI - Primaquine to stop transmission of falciparum malaria. PMID- 26906748 TI - Poisson-Fermi Modeling of the Ion Exchange Mechanism of the Sodium/Calcium Exchanger. AB - The ion exchange mechanism of the sodium/calcium exchanger (NCX) crystallized by Liao et al. in 2012 is studied using the Poisson-Fermi theory developed by Liu and Eisenberg in 2014. A cycle of binding and unbinding is proposed to account for the Na(+)/Ca(2+) exchange function of the NCX molecule. Outputs of the theory include electric and steric fields of ions with different sizes, correlations of ions of different charges, and polarization of water, along with number densities of ions, water molecules, and interstitial voids. We calculate the electrostatic and steric potentials of the four binding sites in NCX, i.e., three Na(+) binding sites and one Ca(2+) binding site, with protein charges provided by the software PDB2PQR. The energy profiles of Na(+) and Ca(2+) ions along their respective Na(+) and Ca(2+) pathways in experimental conditions enable us to explain the fundamental mechanism of NCX that extrudes intracellular Ca(2+) across the cell membrane against its chemical gradient by using the downhill gradient of Na(+). Atomic and numerical details of the binding sites are given to illustrate the 3 Na(+):1 Ca(2+) stoichiometry of NCX. The protein NCX is a catalyst. It does not provide (free) energy for transport. All energy for transport in our model comes from the ions in surrounding baths. PMID- 26906747 TI - Primaquine to reduce transmission of Plasmodium falciparum malaria in Mali: a single-blind, dose-ranging, adaptive randomised phase 2 trial. AB - BACKGROUND: Single low doses of primaquine, when added to artemisinin-based combination therapy, might prevent transmission of Plasmodium falciparum malaria to mosquitoes. We aimed to establish the activity and safety of four low doses of primaquine combined with dihydroartemisinin-piperaquine in male patients in Mali. METHODS: In this phase 2, single-blind, dose-ranging, adaptive randomised trial, we enrolled boys and men with uncomplicated P falciparum malaria at the Malaria Research and Training Centre (MRTC) field site in Ouelessebougou, Mali. All participants were confirmed positive carriers of gametocytes through microscopy and had normal function of glucose-6-phosphate dehydrogenase (G6PD) on colorimetric quantification. In the first phase, participants were randomly assigned (1:1:1) to one of three primaquine doses: 0 mg/kg (control), 0.125 mg/kg, and 0.5 mg/kg. Randomisation was done with a computer-generated randomisation list (in block sizes of six) and concealed with sealed, opaque envelopes. In the second phase, different participants were sequentially assigned (1:1) to 0.25 mg/kg primaquine or 0.0625 mg/kg primaquine. Primaquine tablets were dissolved into a solution and administered orally in a single dose. Participants were also given a 3 day course of dihydroartemisinin-piperaquine, administered by weight (320 mg dihydroartemisinin and 40 mg piperaquine per tablet). Outcome assessors were masked to treatment allocation, but participants were permitted to find out group assignment. Infectivity was assessed through membrane-feeding assays, which were optimised through the beginning part of phase one. The primary efficacy endpoint was the mean within-person percentage change in mosquito infectivity 2 days after primaquine treatment in participants who completed the study after optimisation of the infectivity assay, had both a pre treatment infectivity measurement and at least one follow-up infectivity measurement, and who were given the correct primaquine dose. The safety endpoint was the mean within-person change in haemoglobin concentration during 28 days of study follow-up in participants with at least one follow-up visit. This study is registered with ClinicalTrials.gov, number NCT01743820. FINDINGS: Between Jan 2, 2013, and Nov 27, 2014, we enrolled 81 participants. In the primary analysis sample (n=71), participants in the 0.25 mg/kg primaquine dose group (n=15) and 0.5 mg/kg primaquine dose group (n=14) had significantly lower mean within-person reductions in infectivity at day 2-92.6% (95% CI 78.3-100; p=0.0014) for the 0.25 mg/kg group; and 75.0% (45.7-100; p=0.014) for the 0.5 mg/kg primaquine group compared with those in the control group (n=14; 11.3% [-27.4 to 50.0]). Reductions were not significantly different from control for participants assigned to the 0.0625 mg/kg dose group (n=16; 41.9% [1.4-82.5]; p=0.16) and the 0.125 mg/kg dose group (n=12; 54.9% [13.4-96.3]; p=0.096). No clinically meaningful or statistically significant drops in haemoglobin were recorded in any individual in the haemoglobin analysis (n=70) during follow-up. No serious adverse events were reported and adverse events did not differ between treatment groups. INTERPRETATION: A single dose of 0.25 mg/kg primaquine, given alongside dihydroartemisinin-piperaquine, was safe and efficacious for the prevention of P falciparum malaria transmission in boys and men who are not deficient in G6PD. Future studies should assess the safety of single-dose primaquine in G6PD deficient individuals to define the therapeutic range of primaquine to enable the safe roll-out of community interventions with primaquine. FUNDING: Bill & Melinda Gates Foundation. PMID- 26906750 TI - [Not Available]. PMID- 26906749 TI - A Novel Method to Simulate the Progression of Collagen Degeneration of Cartilage in the Knee: Data from the Osteoarthritis Initiative. AB - We present a novel algorithm combined with computational modeling to simulate the development of knee osteoarthritis. The degeneration algorithm was based on excessive and cumulatively accumulated stresses within knee joint cartilage during physiological gait loading. In the algorithm, the collagen network stiffness of cartilage was reduced iteratively if excessive maximum principal stresses were observed. The developed algorithm was tested and validated against experimental baseline and 4-year follow-up Kellgren-Lawrence grades, indicating different levels of cartilage degeneration at the tibiofemoral contact region. Test groups consisted of normal weight and obese subjects with the same gender and similar age and height without osteoarthritic changes. The algorithm accurately simulated cartilage degeneration as compared to the Kellgren-Lawrence findings in the subject group with excess weight, while the healthy subject group's joint remained intact. Furthermore, the developed algorithm followed the experimentally found trend of cartilage degeneration in the obese group (R(2) = 0.95, p < 0.05; experiments vs. model), in which the rapid degeneration immediately after initiation of osteoarthritis (0-2 years, p < 0.001) was followed by a slow or negligible degeneration (2-4 years, p > 0.05). The proposed algorithm revealed a great potential to objectively simulate the progression of knee osteoarthritis. PMID- 26906752 TI - [Not Available]. PMID- 26906753 TI - [Not Available]. PMID- 26906754 TI - [Not Available]. PMID- 26906756 TI - [Not Available]. PMID- 26906757 TI - [Not Available]. PMID- 26906759 TI - A lateral thoracotomy approach for thoracic duct cannulation and lymphatic fluid collection in a feline model. AB - This study describes a lateral thoracotomy approach for thoracic duct cannulation and lymphatic fluid collection in a feline model. The thoracic duct was cannulated via a left lateral intercostal thoracotomy in 12 cats. Lymphatic fluid was collected for up to 16 days and analyzed on days 3, 9 and 16. The volume collected and duration of cannula patency were recorded. Contrast imaging of the thoracic duct was performed if fluid ceased to flow or at the end of the 16-day study period. In two cats, the cannula became dislodged within 24 h. For the remaining 10 cats, mean daily volume collected was 43.7 mL (median 41.0, range 2.3 to 152.4 mL), and mean duration of cannula patency was 8.2 days (median 6.5, range 3 to 16 days). Contrast imaging revealed that the cannula was patent in three cats, obstructed in two cats, and the thoracic duct had ruptured or had extravasation of contrast outside the duct in five cats. Cytological examination of lymphatic fluid from the three time points revealed normal appearing small lymphocytes (97%) and few (3%) non-degenerate neutrophils, macrophages, eosinophils, and plasma cells. Based on the results of this study, lateral thoracotomy approach for thoracic duct cannulation is a feasible technique for collecting lymphatic fluid in cats. This technique may have application as a model for short-term evaluation of thoracic fluid in cats; however, cannula patency was unpredictable and should be considered when utilizing this technique. PMID- 26906758 TI - Histone H3 N-terminal acetylation sites especially K14 are important for rDNA silencing and aging. AB - Histone variants and histone modifications are essential components in the establishment and maintenance of the repressed status of heterochromatin. Among these histone variants and modifications, acetylation at histone H4K16 is uniquely important for the maintenance of silencing at telomere and mating type loci but not at the ribosomal DNA locus. Here we show that mutations at H3 N terminal acetylation site K14 specifically disrupt rDNA silencing. However, the mutant ion at H3K14R doesn't affect the recruitment of Pol II repressor RENT (regulator of nucleolar silencing and telophase exit) complex at the rDNA region. Instead, the CAF-1(chromatin assembly factor I) subunit Cac2 level decreased in the H3K14R mutant. Further experiments revealed that the single mutation at H3K14 and multi-site mutations at H3 N-terminus including K14 also delayed replication depend nucleosome assembly and advanced replicative life span. In conclusion, our data suggest that histone H3 N-terminal acetylation sites especially at K14 are important for rDNA silencing and aging. PMID- 26906760 TI - Effects of pre-natal alcohol exposure on hippocampal synaptic plasticity: Sex, age and methodological considerations. AB - The consumption of alcohol during gestation is detrimental to the developing central nervous system (CNS). The severity of structural and functional brain alterations associated with alcohol intake depends on many factors including the timing and duration of alcohol consumption. The hippocampal formation, a brain region implicated in learning and memory, is highly susceptible to the effects of developmental alcohol exposure. Some of the observed effects of alcohol on learning and memory may be due to changes at the synaptic level, as this teratogen has been repeatedly shown to interfere with hippocampal synaptic plasticity. At the molecular level alcohol interferes with receptor proteins and can disrupt hormones that are important for neuronal signaling and synaptic plasticity. In this review we examine the consequences of prenatal and early postnatal alcohol exposure on hippocampal synaptic plasticity and highlight the numerous factors that can modulate the effects of alcohol. We also discuss some potential mechanisms responsible for these changes as well as emerging therapeutic avenues that are beginning to be explored. PMID- 26906761 TI - Molecular biomarkers of depression. AB - Depression is the leading psychiatric disorder worldwide with a significant economic and emotional strain on society. There is a need for robust biomarkers which will help improve diagnosis and accelerate the drug discovery process. These are objective, peripheral physiological indicators whose presence can be used to predict the probability of onset or presence of depression, stratify according to severity or symptomatology, indicate prognosis and predict or track response to therapeutic interventions. In this review, we will address several issues pertaining to biomarkers in depression which will be grouped under the headings transcriptomic, proteomic, genomic and telomeric biomarkers. We will review some of the main pitfalls and also address ethical, moral and legal issues which relate to biomarker use in the clinic. We anticipate that in conjunction with initiatives such as the NIH Research Domain Criteria (RDoC), biomarkers will have a significant role to play in the psychiatric clinic in the years to come with a view to improving the lives of sufferers worldwide. PMID- 26906762 TI - Gap locations influence the release of carbon, nitrogen and phosphorus in two shrub foliar litter in an alpine fir forest. AB - Gap formation favors the growth of understory plants and affects the decomposition process of plant debris inside and outside of gaps. Little information is available regarding how bioelement release from shrub litter is affected by gap formation during critical periods. The release of carbon (C), nitrogen (N), and phosphorus (P) in the foliar litter of Fargesia nitida and Salix paraplesia in response to gap locations was determined in an alpine forest of the eastern Qinghai-Tibet Plateau via a 2-year litter decomposition experiment. The daily release rates of C, N, and P increased from the closed canopy to the gap centers during the two winters, the two later growing seasons and the entire 2 years, whereas this trend was reversed during the two early growing seasons. The pairwise ratios among C, N, and P converged as the litter decomposition proceeded. Compared with the closed canopy, the gap centers displayed higher C:P and N:P ratio but a lower C:N ratio as the decomposition proceeded. Alpine forest gaps accelerate the release of C, N, and P in decomposing shrub litter, implying that reduced snow cover resulting from vanishing gaps may inhibit the release of these elements in alpine forests. PMID- 26906763 TI - Relapse: What Should We Do About It? Commentary on Flynn and Brown (2016). PMID- 26906764 TI - Broadband near-field infrared spectromicroscopy using photothermal probes and synchrotron radiation. AB - In this paper, we experimentally demonstrate the use of infrared synchrotron radiation (IR-SR) as a broadband source for photothermal near-field infrared spectroscopy. We assess two methods of signal transduction; cantilever resonant thermal expansion and scanning thermal microscopy. By means of rapid mechanical chopping (50-150 kHz), we modulate the IR-SR at rates matching the contact resonance frequencies of atomic force microscope (AFM) cantilevers, allowing us to record interferograms yielding Fourier transform infrared (FT-IR) photothermal absorption spectra of polystyrene and cyanoacrylate films. Complementary offline measurements using a mechanically chopped CW IR laser confirmed that the resonant thermal expansion IR-SR measurements were below the diffraction limit, with a spatial resolution better than 500 nm achieved at a wavelength of 6 MUm, i.e. lambda/12 for the samples studied. Despite achieving the highest signal to noise so far for a scanning thermal microscopy measurement under conditions approaching near-field (dictated by thermal diffusion), the IR-SR resonant photothermal expansion FT-IR spectra measured were significantly higher in signal to noise in comparison with the scanning thermal data. PMID- 26906765 TI - Ultra-low temperature silicon nitride photonic integration platform. AB - High-quality SiNx films with controllable low stress and low optical loss are deposited at ultra-low temperature (75 degrees C) using inductively coupled plasma chemical vapor deposition (ICP-CVD). Two kinds of integrated photonic structures have been demonstrated that exemplify its viability as a photonic integration platform. A microcavity consists of two distributed Bragg reflectors (DBR) formed by alternating a total of 49 layers of SiNx and SiO2 with a total thickness of about 11.5 MUm is grown without any cracks, confirming the excellent stress control in the process. Microring resonators are also fabricated in as deposited planar SiNx waveguide layer using electron-beam lithography (EBL) and plasma etching. Average waveguide loss of 0.79 +/- 0.22 dB/cm has been achieved in the range of 1550-1600 nm for ring radii larger than 40 MUm. The ultra-low temperature grown SiNx with properties of low loss and low stress is therefore a promising photonic integration platform for various photonic integration applications. PMID- 26906766 TI - Computational multi-depth single-photon imaging. AB - We present an imaging framework that is able to accurately reconstruct multiple depths at individual pixels from single-photon observations. Our active imaging method models the single-photon detection statistics from multiple reflectors within a pixel, and it also exploits the fact that a multi-depth profile at each pixel can be expressed as a sparse signal. We interpret the multi-depth reconstruction problem as a sparse deconvolution problem using single-photon observations, create a convex problem through discretization and relaxation, and use a modified iterative shrinkage-thresholding algorithm to efficiently solve for the optimal multi-depth solution. We experimentally demonstrate that the proposed framework is able to accurately reconstruct the depth features of an object that is behind a partially-reflecting scatterer and 4 m away from the imager with root mean-square error of 11 cm, using only 19 signal photon detections per pixel in the presence of moderate background light. In terms of root mean-square error, this is a factor of 4.2 improvement over the conventional method of Gaussian-mixture fitting for multi-depth recovery. PMID- 26906767 TI - Dual-comb modelocked lasers: semiconductor saturable absorber mirror decouples noise stabilization. AB - In this paper we present the stabilization of the pulse repetition rate of dual comb lasers using an intracavity semiconductor saturable absorber mirror (SESAM) for passive modelocking and an intracavity birefringent crystal for polarization duplexing to obtain simultaneous emission of two modelocked beams from the same linear cavity sharing all components. Initially surprising was the observation that the cavity length adjustments to stabilize one polarization did not significantly affect the pulse repetition rate of the other. We gained insight in the underlying physics using both a semiconductor and Nd:YAG laser gain material with the conclusion that the pulse arrival timing jitter of the two beams is decoupled by the uncorrelated time delay from the saturated SESAM and becomes locked with sufficient but not too much pulse overlap. Noise stabilization is in all cases still possible for both combs. The dual-comb modelocked laser is particularly interesting for the semiconductor laser enabling the integration of gain and absorber layers within one wafer (referred to as the modelocked integrated external-cavity surface emitting laser--MIXSEL). PMID- 26906768 TI - Dual-mode photosensitive arrays based on the integration of liquid crystal microlenses and CMOS sensors for obtaining the intensity images and wavefronts of objects. AB - In this paper, we present a kind of dual-mode photosensitive arrays (DMPAs) constructed by hybrid integration a liquid crystal microlens array (LCMLA) driven electrically and a CMOS sensor array, which can be used to measure both the conventional intensity images and corresponding wavefronts of objects. We utilize liquid crystal materials to shape the microlens array with the electrically tunable focal length. Through switching the voltage signal on and off, the wavefronts and the intensity images can be acquired through the DMPAs, sequentially. We use white light to obtain the object's wavefronts for avoiding losing important wavefront information. We separate the white light wavefronts with a large number of spectral components and then experimentally compare them with single spectral wavefronts of typical red, green and blue lasers, respectively. Then we mix the red, green and blue wavefronts to a composite wavefront containing more optical information of the object. PMID- 26906769 TI - Controllable design of super-oscillatory planar lenses for sub-diffraction-limit optical needles. AB - Sub-diffraction-limit optical needle can be created by a binary amplitude mask through tailoring the interference of diffraction beams. In this paper, a controllable design of super-oscillatory planar lenses to create sub-diffraction limit optical needles with the tunable focal length and depth of focus (DOF) is presented. As a high-quality optical needle is influenced by various factors, we first propose a multi-objective and multi-constraint optimization model compromising all the main factors to achieve a needle with the prescribed characteristics. The optimizing procedure is self-designed using the Matlab programming language based on the genetic algorithm (GA) and fast Hankel transform algorithm. Numerical simulations show that the optical needles' properties can be controlled accurately. The optimized results are further validated by the theoretical calculation with the Rayleigh-Sommerfeld integral. The sub-diffraction-limit optical needles can be used in wide fields such as optical nanofabrication, super-resolution imaging, particle acceleration and high density optical data storage. PMID- 26906770 TI - Eye-safe diode laser Doppler lidar with a MEMS beam-scanner. AB - We present a novel Doppler lidar that employs a cw diode laser operating at 1.5 MUm and a micro-electro-mechanical-system scanning mirror (MEMS-SM). In this work, two functionalities of the lidar system are demonstrated. Firstly, we describe the capability to effectively steer the lidar probe beam to multiple optical transceivers along separate lines-of-sight. The beam steering functionality is demonstrated using four lines-of-sight--each at an angle of 18 degrees with respect to their symmetry axis. Secondly, we demonstrate the ability to spatially dither the beam focus to reduce the mean irradiance at the probing distance (R = 60 m) of each line-of-sight--elevant for meeting eye-safety requirements. The switching time of the MEMS-SM is measured to be in the order of a few milliseconds. Time-shared (0.25 s per line-of-sight) radial wind speed measurements at 50 Hz data rate are experimentally demonstrated. Spatial dithering of the beam focus is also implemented using a spiral scan trajectory resulting in a 16 dB reduction of beam focus mean irradiance. PMID- 26906771 TI - Voltage sharing effect and interface state calculation of a wafer-bonding Ge/Si avalanche photodiode with an interfacial GeO2 insulator layer. AB - The tunneling effect and interface state in the p-Ge/GeO2p-Si structure of a wafer-bonding Ge/Si avalanche photodiode (APD) are investigated. It is found that the thin interfacial GeO2 layer (1-2 nm) formed by the hydrophilic reaction at the wafer-bonding interface significantly affects the performance of the Ge/Si APD. With the increase of the GeO2 thickness, the dark current of the Ge/Si APD decreases enormously due to the blocking effect of this GeO2 layer. Owing to the carrier accumulation in Ge layer under illumination condition, the voltage sharing effect of the GeO2 layer (thicker) becomes serious, leading to the absence of the electric field in Ge layer. The photon-generated electrons at Ge/GeO2 interface can be captured and released by the interface states at certain reverse bias. This can adjust the avalanche current of the Ge/Si APD. The stronger interface recombination induced by the larger interface state density (ISD) results in the decrease of the electric field in Ge layer. This increases the transit time of carriers, which in turn decreases the 3dB-bandwidth. Due to the drastic increase of the dark current (larger ISD), the gain of the Ge/Si APD decreases. PMID- 26906772 TI - Retrieving the real refractive index of mono- and polydisperse colloids from reflectance near the critical angle. AB - We investigate the accuracy in retrieving the real refractive index of submicron aerosol particles, at a visible wavelength, from near critical angle reflectance measurements of a dilute suspension of the aerosol. A coherent scattering model (CSM) is used to model the coherent reflectance from the colloidal suspension. We use an extension of the model for polydisperse particles to properly account for the modified size distribution close to the incident medium to colloid interface. We perform a rigorous sensitivity analysis, for both the monodisperse and polydisperse models, to determine how experimental uncertainties propagate into uncertainty in the retrieval of real refractive index. The effect of non spherical scattering was included in the sensitivity analysis by using T-matrix methods. Experimental reflectance data, at a wavelength of 635 nm, were obtained for monodisperse spherical latex particles, a polydisperse sand sample and a polydisperse volcanic ash sample. We show that the retrieved real refractive index for these particles is consistent with values obtained using other techniques. PMID- 26906773 TI - Comparison of thresholding schemes for visible light communication using mobile phone image sensor. AB - Based on the rolling shutter effect of the complementary metal-oxide semiconductor (CMOS) image sensor, bright and dark fringes can be observed in each received frame. By demodulating the bright and dark fringes, the visible light communication (VLC) data logic can be retrieved. However, demodulating the bright and dark fringes is challenging as there is a high data fluctuation and large extinction ratio (ER) variation in each frame due. Hence proper thresholding scheme is needed. In this work, we propose and compare experimentally three thresholding schemes; including third-order polynomial curve fitting, iterative scheme and quick adaptive scheme. The evaluation of these three thresholding schemes is performed. PMID- 26906774 TI - First demonstration of SiGe-based carrier-injection Mach-Zehnder modulator with enhanced plasma dispersion effect. AB - We demonstrate a strained Si0.91Ge0.09-based carrier-injection Mach-Zehnder (MZ) optical modulator using the enhanced plasma dispersion effect in strained SiGe through mass modulation for the first time. The SiGe modulator has an injection current of 1.47 mA for a phase shift of pi which is lower than that for a Si modulator. Also, it is expected that the injection current can be further reduced by increasing the strain and Ge fraction, enabling operation at an injection current of less than 1 mA. As an example of the dynamic characteristics, 10 Gbps modulation with clear eye opening was obtained by the pre-emphasis method. PMID- 26906775 TI - Laser spectroscopic studies of gas diffusion in alumina ceramics. AB - Experiments for measuring gas diffusion through porous alumina ceramics are described. With the gas in scattering media absorption spectroscopy (GASMAS) technique, gaseous oxygen signals are measured continuously during the gas diffusion process. It is experimentally demonstrated that the time-dependence of the transient oxygen signal is described by an exponential curve. Moreover, the effect on gas diffusion of material porosity and whether water is present or not is also experimentally investigated. PMID- 26906776 TI - Demonstration of post-growth wavelength setting of VCSELs using high-contrast gratings. AB - We demonstrate, for the first time, post-growth wavelength setting of electrically-injected vertical-cavity surface-emitting lasers (VCSELs) by using high-contrast gratings (HCGs) with different grating parameters. By fabricating HCGs with different duty cycle and period, the HCG reflection phase can be varied, in effect giving different optical cavity lengths for HCG-VCSELs with different grating parameters. This enables fabrication of monolithic multi wavelength HCG-VCSEL arrays for wavelength-division multiplexing (WDM). The GaAs HCG is suspended in air by removing a sacrificial layer of InGaP. Electrically injected 980-nm HCG-VCSELs with sub-mA threshold currents indicate high reflectivity from the GaAs HCGs. Lasing over a wavelength span of 15 nm was achieved, enabling a 4-channel WDM array with 5 nm channel spacing. A large wavelength setting span was enabled by an air-coupled cavity design and the use of only the HCG as top mirror. PMID- 26906777 TI - Hyperspectral optical diffraction tomography. AB - Here, we present a novel microscopic technique for measuring wavelength-dependent three-dimensional (3-D) distributions of the refractive indices (RIs) of microscopic samples in the visible wavelengths. Employing 3-D quantitative phase microscopy techniques with a wavelength-swept source, 3-D RI tomograms were obtained in the range of 450 - 700 nm with a spectral resolution of a few nanometers. The capability of the technique was demonstrated by measuring the hyperspectral 3-D RI tomograms of polystyrene beads, human red blood cells, and hepatocytes. The results demonstrate the potential for label-free molecular specific 3-D tomography of biological samples. PMID- 26906778 TI - COMPU-EYE: a high resolution computational compound eye. AB - In nature, the compound eyes of arthropods have evolved towards a wide field of view (FOV), infinite depth of field and fast motion detection. However, compound eyes have inferior resolution when compared with the camera-type eyes of vertebrates, owing to inherent structural constraints such as the optical performance and the number of ommatidia. For resolution improvements, in this paper, we propose COMPUtational compound EYE (COMPU-EYE), a new design that increases acceptance angles and uses a modern digital signal processing (DSP) technique. We demonstrate that the proposed COMPU-EYE provides at least a four fold improvement in resolution. PMID- 26906779 TI - Lattice Boltzmann method for one-dimensional vector radiative transfer. AB - A one-dimensional vector radiative transfer (VRT) model based on lattice Boltzmann method (LBM) that considers polarization using four Stokes parameters is developed. The angular space is discretized by the discrete-ordinates approach, and the spatial discretization is conducted by LBM. LBM has such attractive properties as simple calculation procedure, straightforward and efficient handing of boundary conditions, and capability of stable and accurate simulation. To validate the performance of LBM for vector radiative transfer, four various test problems are examined. The first case investigates the non scattering thermal-emitting atmosphere with no external collimated solar. For the other three cases, the external collimated solar and three different scattering types are considered. Particularly, the LBM is extended to solve VRT in the atmospheric aerosol system where the scattering function contains singularities and the hemisphere space distributions for the Stokes vector are presented and discussed. The accuracy and computational efficiency of this algorithm are discussed. Numerical results show that the LBM is accurate, flexible and effective to solve one-dimensional polarized radiative transfer problems. PMID- 26906780 TI - Controlling magnetic and electric dipole modes in hollow silicon nanocylinders. AB - We propose a dielectric nanoresonator geometry consisting of hollow dielectric nanocylinders which support geometrical resonances. We fabricate such hollow Si particles with an outer diameter of 108-251 nm on a Si substrate, and determine their resonant modes with cathodo-luminescence (CL) spectroscopy and optical dark field (DF) scattering measurements. The scattering behavior is numerically investigated in a systematic fashion as a function of wavelength and particle geometry. We find that the additional design parameter as a result of the introduction of a center gap can be used to control the relative spectral spacing of the resonant modes, which will enable additional control over the angular radiation pattern of the scatterers. Furthermore, the gap offers direct access to the enhanced magnetic dipole modal field in the center of the particle. PMID- 26906781 TI - Terahertz field enhancement in asymmetric and tapered nano-gaps. AB - We investigate field enhancement inside metal-insulator-metal gaps with asymmetric thicknesses and tapered shapes in the terahertz regime. Finite difference time-domain simulations were conducted for calculation of field enhancement factor. The calculation indicates that for asymmetric sample, field enhancement increases proportionally with the decrease of the thinner of the two metal film thicknesses surrounding the gap. Concomitantly, angle variation has little effect on the field enhancement if the thickness of the narrowest gap region is fixed. A model based on the capacitor concept is proposed for intuitive understanding of the phenomena. PMID- 26906782 TI - Integral imaging microscopy with enhanced depth-of-field using a spatial multiplexing. AB - A depth-of-field enhancement method for integral imaging microscopy system using a spatial multiplexing structure consisting of a beamsplitter with dual video channels and micro lens arrays is proposed. A computational integral imaging reconstruction algorithm generates two sets of depth-sliced images for the acquired depth information of the captured elemental image arrays and the well focused depth-slices of both image sets are combined where each is focused on a different depth plane of the specimen. A prototype is implemented, and the experimental results demonstrate that the depth-of-field of the reconstructed images in the proposed integral imaging microscopy is significantly increased compared with conventional integral imaging microscopy systems. PMID- 26906783 TI - Markov chain Monte Carlo methods for statistical analysis of RF photonic devices. AB - The microwave reflection coefficient is commonly used to characterize the impedance of high-speed optoelectronic devices. Error and uncertainty in equivalent circuit parameters measured using this data are systematically evaluated. The commonly used nonlinear least-squares method for estimating uncertainty is shown to give unsatisfactory and incorrect results due to the nonlinear relationship between the circuit parameters and the measured data. Markov chain Monte Carlo methods are shown to provide superior results, both for individual devices and for assessing within-die variation. PMID- 26906784 TI - Adjustable liquid aperture to eliminate undesirable light in holographic projection. AB - In this paper, we propose an adjustable liquid aperture to eliminate the undesirable light in a holographic projection. The aperture is based on hydrodynamic actuation. A chamber is formed with a cylindrical tube. A black droplet is filled in the sidewall of the cylinder tube and the outside space is the transparent oil which is immiscible with the black droplet. An ultrathin glass sheet is attached on the bottom substrate of the device and a black shading film is secured to the central area of the glass sheet. By changing the volume of the black droplet, the black droplet will move to the middle or sidewall due to hydrodynamic actuation, so the device can be used as an adjustable aperture. A divergent spherical wave and a solid lens are used to separate the focus planes of the reconstructed image and diffraction beams induced by the liquid crystal on silicon in the holographic projection. Then the aperture is used to eliminate the diffraction beams by adjusting the size of the liquid aperture and the holographic projection does not have undesirable light. PMID- 26906785 TI - Contradiction within wave optics and its solution within a particle picture: comment. AB - An error in the rationale presented in the paper "Contradiction within wave optics and its solution within a particle picture" by Altmann [Opt. Express 23, 3731 (2015)10.1364/OE.23.003731] is discussed. PMID- 26906786 TI - Contradiction within wave optics and its solution within a particle picture: reply. AB - The comment on the paper "Contradiction within wave optics and its solution within a particle picture," [Opt. Express 23, 3731 (2015)10.1364/OE.23.003731] is discussed. PMID- 26906787 TI - Hybrid nonlinear surface-phonon-plasmon-polaritons at the interface of nolinear medium and graphene-covered hexagonal boron nitride crystal. AB - The properties of hybrid nonlinear surface-phonon-plasmon-polaritons (SP3) at the interface of nonlinear medium and graphene-covered hexagonal boron nitride (hBN) are investigated theoretically. It is demonstrated that the hybrid nonlinear SP3 can be tuned by controlling the chemical potential, layer number and relaxation time of graphene. The real and imaginary parts of the propagation constant increase by decreasing the Fermi energy or the layer number of the graphene in the frequency outside of the upper Reststrahlen band of hBN. Moreover, we show that the nonlinear dielectric permittivity has great effect on the propagation constant. The real part of the propagation constant increases with positive nonlinear dielectric permittivity at different frequency for low frequency mode; while the imaginary part of the propagation constant decreases in the upper Reststrahlen band of hBN, keeps nearly constant in the lower band, and increases outside the Reststrahlen band with positive nonlinear dielectric permittivity for low frequency mode. PMID- 26906788 TI - Generation of multi-mode squeezed vacuum using pulse pumped fiber optical parametric amplifiers. AB - Multimode squeezed states are essential resources in quantum information processing and quantum metrology with continuous variables. Here we present the experimental generation of squeezed vacuum via the degenerate four wave mixing realized by pumping a piece of dispersion shifted fiber with mode-locked ultrafast pulse trains. The noise fluctuation is lower than the shot noise limit by 1.1 +/- 0.08 dB (1.95 +/- 0.17 dB after correction for detection losses). The detailed investigation illustrates that the results can be further improved by suppressing Raman scattering and by reshaping the spectrum of the local oscillator to achieve the required mode-matching of the homodyne detection system. Our study is useful for developing a compact fiber source of multi-mode squeezed vacuum. PMID- 26906789 TI - Atmospheric correction with the Bayesian empirical line. AB - Atmospheric correction of visible/infrared spectra traditionally involves either (1) physics-based methods using Radiative Transfer Models (RTMs), or (2) empirical methods using in situ measurements. Here a more general probabilistic formulation unifies the approaches and enables combined solutions. The technique is simple to implement and provides stable results from one or more reference spectra. This makes empirical corrections practical for large or remote environments where it is difficult to acquire coincident field data. First, we use a physics-based solution to define a prior distribution over reflectances and their correction coefficients. We then incorporate reference measurements via Bayesian inference, leading to a Maximum A Posteriori estimate which is generally more accurate than pure physics-based methods yet more stable than pure empirical methods. Gaussian assumptions enable a closed form solution based on Tikhonov regularization. We demonstrate performance in atmospheric simulations and historical data from the "Classic" Airborne Visible Infrared Imaging Spectrometer (AVIRIS-C) acquired during the HyspIRI mission preparatory campaign. PMID- 26906791 TI - Cooperative optical response of 2D dense lattices with strongly correlated dipoles. AB - We study light propagation in dense low-temperature atoms on two-dimensional (2D) square and kagome lattices using a basically exact large-scale numerical computations. In the limit of weak laser intensity, shifts of the resonance line are shown in homogeneously broadened stationary samples with high atom densities, whereas the shifts are not shown in the samples with low densities. We obtain the dependence of shifts on interatomic spacing for square lattices with the various numbers of atoms, and our numerical results are in good agreement with shifts derived using a 2D isotropic infinite lattice model and experimental data for nanometric-thickness atomic ensembles in the literature. PMID- 26906790 TI - Integrated monolithic 3D MEMS scanner for switchable real time vertical/horizontal cross-sectional imaging. AB - We present an integrated monolithic, electrostatic 3D MEMS scanner with a compact chip size of 3.2 * 2.9 mm(2). Use of parametric excitation near resonance frequencies produced large optical deflection angles up to +/- 27 degrees and +/ 28.5 degrees in the X- and Y-axes and displacements up to 510 MUm in the Z-axis with low drive voltages at atmospheric pressure. When packaged in a dual axes confocal endomicroscope, horizontal and vertical cross-sectional images can be collected seamlessly in tissue with a large field-of-view of >1 * 1 mm(2) and 1 * 0.41 mm(2), respectively, at 5 frames/sec. PMID- 26906792 TI - Non-destructive splitter of twisted light based on modes splitting in a ring cavity. AB - Efficiently discriminating beams carrying different orbital angular momentum (OAM) is of fundamental importance for various applications including high capacity optical communication and quantum information processing. We design and experimentally verify a distinguished method for effectively splitting different OAM-carried beams by introducing Dove prisms in a ring cavity. Because of rotational symmetry broken of two OAM-carried beams with opposite topological charges, their transmission spectra will split. When mode and impedance matches between the cavity and one OAM-carried beam are achieved, this beam will transmit through the cavity and other beam will be reflected, both beams keep their spatial shapes. In this case, the cavity acts like a polarized beam splitter. Besides, the transmitting beam can be selected at your will, the splitting efficiency can reach unity if the cavity is lossless and it completely matches the beam. Furthermore, beams carry multi-OAMs can also be split by cascading ring cavities. PMID- 26906793 TI - Engineered far-fields of metal-metal terahertz quantum cascade lasers with integrated planar horn structures. AB - The far-field emission profile of terahertz quantum cascade lasers (QCLs) in metal-metal waveguides is controlled in directionality and form through planar horn-type shape structures, whilst conserving a broad spectral response. The structures produce a gradual change in the high modal confinement of the waveguides and permit an improved far-field emission profile and resulting in a four-fold increase in the emitted output power. The two-dimensional far-field patterns are measured at 77 K and are agreement in with 3D modal simulations. The influence of parasitic high-order transverse modes is shown to be controlled by engineering the horn structure (ridge and horn widths), allowing only the fundamental mode to be coupled out. PMID- 26906794 TI - Wavelength and bandwidth-tunable silicon comb filter based on Sagnac loop mirrors with Mach-Zehnder interferometer couplers. AB - We propose and experimentally demonstrate a wavelength and bandwidth-tunable comb filter based on silicon Sagnac loop mirrors (SLMs) with Mach-Zehnder interferometer (MZI) couplers. By thermally tuning the MZI couplers in common and differential modes, the phase shift and reflectivity of the SLMs can be changed, respectively, leading to tunable wavelength and bandwidth of the comb filter. The fabricated comb filter has 93 comb lines in the wavelength range from 1535 nm to 1565 nm spaced by ~0.322 nm. The central wavelength can be red-shifted by ~0.462 nm with a tuning efficiency of ~0.019 nm/mW. A continuously tunable bandwidth from 5.88 GHz to 24.89 GHz is also achieved with a differential heating power ranging from 0.00 mW to 0.53 mW. PMID- 26906795 TI - Color holographic display with white light LED source and single phase only SLM. AB - This work presents color holographic display, which is based on a single phase only spatial light modulator (SLM). In the display entire area of the SLM is illuminated by an on-axis white light beam generated by a single large LED. The holographic display fully utilizes SLM bandwidth and has capability of full color, full frame rate imaging of outstanding quality. This is achieved through: (i) optimal use of the source coherence volume, (ii) application of the single white light LED source, (iii) a development of a novel concept of color multiplexing technique with color filter mask in Fourier plane of the SLM, (iv) and a complex coding with improved diffraction efficiency. Within experimental part of the paper we show single color, full-color holographic 2D and 3D images generated for reconstruction depth exceeding 10 cm. PMID- 26906796 TI - Parallel-mode scanning optical sectioning using digital Fresnel holography with three-wave interference phase-shifting. AB - The Fresnel incoherent correlation holography (FINCH) method is applicable to various techniques of imaging, including fluorescence microscopy. Recently, a FINCH configuration capable of optical sectioning, using a scanning phase pinhole, has been suggested [Optica 1, 70 (2014)]. This capability is highly important in situations that demand the suppression of out-of-focus information from the hologram reconstruction of a specific plane of interest, such as the imaging of thick samples in biology. In this study, parallel-mode scanning using multiple phase pinholes is suggested as a means to shorten the acquisition time in an optical sectioning FINCH configuration. The parallel-mode scanning is enabled through a phase-shifting procedure that extracts the mixed term of two out of three interfering beams. PMID- 26906797 TI - Transmission performance improvement using random DFB laser based Raman amplification and bidirectional second-order pumping. AB - We demonstrate that a distributed Raman amplification scheme based on random distributed feedback (DFB) fiber laser enables bidirectional second-order Raman pumping without increasing relative intensity noise (RIN) of the signal. This extends the reach of 10 * 116 Gb/s DP-QPSK WDM transmission up to 7915 km, compared with conventional Raman amplification schemes. Moreover, this scheme gives the longest maximum transmission distance among all the Raman amplification schemes presented in this paper, whilst maintaining relatively uniform and symmetric signal power distribution, and is also adjustable in order to be highly compatible with different nonlinearity compensation techniques, including mid link optical phase conjugation (OPC) and nonlinear Fourier transform (NFT). PMID- 26906798 TI - Diagnostic potential of polarized surface enhanced Raman spectroscopy technology for colorectal cancer detection. AB - The purpose of this study was to develop a more powerful blood analysis method based on polarized surface enhanced Raman spectroscopy (SERS) technology for non invasive and sensitive colorectal cancer (CRC) detection. The efficiency of different polarized scattering signals (non-polarization, parallel polarization and perpendicular polarization) on blood serum SERS was explored for the first time. Results demonstrated that polarized SERS was more sensitive to explore distinctive spectral differences between cancer and normal groups. And higher diagnostic accuracy of 91.6% could be achieved using polarized SERS integrated with PCA-LDA for classification of the two serum groups in comparison to conventional SERS technology. This exploratory study demonstrated that the nanobiosensor based on polarized SERS technique in conjunction with PCA-LDA provided a novel strategy for blood SERS analysis, and had the potential as a clinical complement for CRC screening. PMID- 26906799 TI - Strong optical force acting on a dipolar particle over a multilayer substrate. AB - Optical forces acting on nano-sized particles are typically too small to be useful for particle manipulation. We theoretically and numerically demonstrate a mechanism that can significantly enhance the optical force acting on a small particle through a special type of resonant particle-substrate coupling. The resonance arises from the singular behavior of the particle's effective polarizablity in the presence of a metal-dielectric-metal multilayer substrate. We show that this phenomenon is closely related to the existence of a flat-band plasmon mode supported by the multilayer substrate. PMID- 26906800 TI - Relation between 2D/3D chirality and the appearance of chiroptical effects in real nanostructures. AB - The optical activity of fabricated metallic nanostructures is investigated by complete polarimetry. While lattices decorated with nanoscale gammadia etched in thin metallic films have been described as two dimensional, planar nanostructures, they are better described as quasi-planar structures with some three dimensional character. We find that the optical activity of these structures arises not only from the dissymmetric backing by a substrate but, more importantly, from the selective rounding of the nanostructure edges. A true chiroptical response in the far-field is only allowed when the gammadia contain these non-planar features. This is demonstrated by polarimetric measurements in conjunction with electrodynamical simulations based on the discrete dipole approximation that consider non-ideal gammadia. It is also shown that subtle planar dissymmetries in gammadia are sufficient to generate asymmetric transmission of circular polarized light. PMID- 26906801 TI - Unidirectional emission from a cardioid-shaped microcavity laser. AB - We find unidirectional emission in a cardioid-shaped microcavity laser. When a deformation parameter is well adjusted, rays starting around a period-5 unstable periodic orbit emit unidirectionally. To confirm the emission direction, we fabricate a laser by using an InGaAsP semiconductor and investigate emission characteristics. When the laser is excited by current injection with a dc current, resonances localized on the period-5 unstable periodic orbit emit unidirectionally. PMID- 26906802 TI - Singularimetry of local phase gradients using vortex lattices and in-line holography. AB - We have developed a differential form of singularimetry, which utilizes phase vortices or intensity gradient singularities as topological fiducial markers in a structured illumination context. This approach analytically measures phase gradients imparted by refracting specimens, yielding quantitative information that is both local and deterministic. We have quantified our phase gradient experiments to demonstrate that lattices of wave field singularities can be used to detect subtle phase gradients imparted by a spherical specimen and fiber optic cylinders. PMID- 26906803 TI - RGB and white-emitting organic lasers on flexible glass. AB - Two formats of multiwavelength red, green and blue (RGB) laser on mechanically flexible glass are demonstrated. In both cases, three all-organic, vertically emitting distributed feedback (DFB) lasers are assembled onto a common ultra-thin glass membrane substrate and fully encapsulated by a thin polymer overlayer and an additional 50 um-thick glass membrane in order to improve the performance. The first device format has the three DFB lasers sitting next to each other on the glass substrate. The DFB lasers are simultaneously excited by a single overlapping optical pump, emitting spatially separated red, green and blue laser output with individual thresholds of, respectively, 28 uJ/cm(2), 11 uJ/cm(2) and 32 uJ/cm(2) (for 5 ns pump pulses). The second device format has the three DFB lasers, respectively the red, green and blue laser, vertically stacked onto the flexible glass. This device format emits a white laser output for an optical pump fluence above 42 uJ/cm(2). PMID- 26906804 TI - Tunable cw UV laser with <35 kHz absolute frequency instability for precision spectroscopy of Sr Rydberg states. AB - We present a solid-state laser system that generates over 200 mW of continuous wave, narrowband light, tunable from 316.3 nm - 317.7 nm and 318.0 nm - 319.3 nm. The laser is based on commercially available fiber amplifiers and optical frequency doubling technology, along with sum frequency generation in a periodically poled stoichiometric lithium tantalate crystal. The laser frequency is stabilized to an atomic-referenced high finesse optical transfer cavity. Using a GPS-referenced optical frequency comb we measure a long term frequency instability of < 35 kHz for timescales between 10(-3) s and 10(3) s. As an application we perform spectroscopy of Sr Rydberg states from n = 37 - 81, demonstrating mode-hop-free scans of 24 GHz. In a cold atomic sample we measure Doppler-limited linewidths of 350 kHz. PMID- 26906805 TI - Shannon entropy method of small-scale self-focusing assessment in high-power laser systems. AB - Through analysis of near-field beam profiles, we propose a method using Shannon entropy to assess the development of small-scale self-focusing during laser propagation and amplification in high-power laser systems. In this method, the entropy curve that corresponds to increasing B integral displays an evident turning point at which small-scale self-focusing starts to rapidly develop. In contrast to classical methods using contrast, modulation, or power spectral density, the proposed method provides the B integral criterion more clearly and objectively. This approach is an optimization method that can be utilized in the design and operation of high-power laser systems. PMID- 26906806 TI - Flexible and re-configurable optical three-input XOR logic gate of phase modulated signals with multicast functionality for potential application in optical physical-layer network coding. AB - Optical logic gate, especially exclusive-or (XOR) gate, plays important role in accomplishing photonic computing and various network functionalities in future optical networks. On the other hand, optical multicast is another indispensable functionality to efficiently deliver information in optical networks. In this paper, for the first time, we propose and experimentally demonstrate a flexible optical three-input XOR gate scheme for multiple input phase-modulated signals with a 1-to-2 multicast functionality for each XOR operation using four-wave mixing (FWM) effect in single piece of highly-nonlinear fiber (HNLF). Through FWM in HNLF, all of the possible XOR operations among input signals could be simultaneously realized by sharing a single piece of HNLF. By selecting the obtained XOR components using a followed wavelength selective component, the number of XOR gates and the participant light in XOR operations could be flexibly configured. The re-configurability of the proposed XOR gate and the function integration of the optical logic gate and multicast in single device offer the flexibility in network design and improve the network efficiency. We experimentally demonstrate flexible 3-input XOR gate for four 10-Gbaud binary phase-shift keying signals with a multicast scale of 2. Error-free operations for the obtained XOR results are achieved. Potential application of the integrated XOR and multicast function in network coding is also discussed. PMID- 26906807 TI - Plasmonic chirality of L-shaped nanostructure composed of two slices with different thickness. AB - A concise method is proposed to fabricate L-shaped Ag nanostructures (LSANs) for generating chirality. Prepared by glancing angle deposition, the LSAN composed of two slices with different thickness is stacked on self-assembled monolayer polystyrene nanosphere arrays by controlling substrate azimuth and deposition time. The strong optical chirality of LSANs is achieved in visible and near-IR regions by measurement. For the circular dichroism spectrum of LSANs, the intensity is enlarged, and its peaks red-shift with increasing thickness difference. When LSANs are stacked on polystyrene spheres of different diameters, enlargement and red-shift are also observed in their circular dichroism spectra with increasing thickness difference. The numerical calculations of finite element method show that the two slices composing LSAN provide cross-electric dipoles and their thickness difference provides phase difference for generating optical chirality. This study not only provides a concise and scalable method for fabricating chiral plasmonic nanostructures but also contributes to understand the knowledge of the mechanism of circular dichroism. PMID- 26906808 TI - Higher order correlation beams in atmosphere under strong turbulence conditions. AB - Higher order correlation beams, that is, two-photon beams obtained from the process of spontaneous parametric down-conversion pumped by Hermite-Gauss or Laguerre-Gauss beams of any order, can be used to encode information in many modes, opening the possibility of quantum communication with large alphabets. In this paper we calculate, analytically, the fourth-order correlation function for the Hermite-Gauss and Laguerre-Gauss coherent and partially coherent correlation beams propagating through a strong turbulent medium. We show that fourth-order correlation functions for correlation beams have, under certain conditions, expressions similar to those of intensities of classical beams and are degraded by turbulence in a similar way as the classical beams. Our results can be useful in establishing limits for the use of two-photon beams in quantum communications with larger alphabets under atmospheric turbulence. PMID- 26906809 TI - Vector similariton erbium-doped all-fiber laser generating sub-100-fs nJ pulses at 100 MHz. AB - Erbium-doped mode-locked fiber lasers with repetition rates comparable to those of solid-state lasers and generating nJ pulses are required for many applications. Our goal was to design a fiber laser that would meet such requirements, that could be built at relatively low cost and that would be reliable and robust. We thus developed a high-fundamental-repetition-rate erbium doped all-fiber laser operating in the amplifier similariton regime. Experimental characterization shows that this laser, which is mode-locked by nonlinear polarization evolution, emits 76-fs pulses with an energy of 1.17 nJ at a repetition rate of 100 MHz. Numerical simulations support the interpretation of self-similar evolution of the pulse in the gain fiber. More specifically we introduce the concept of vector similariton in fiber lasers. The coupled x- and y polarization components of such a pulse have a pulse profile with a linear chirp and their combined power profile evolves self-similarly when the nonlinear asymptotic regime is reached in the gain fiber. PMID- 26906810 TI - Improvement of vacuum squeezing resonant on the rubidium D1 line at 795 nm. AB - We report on efficient generation of second harmonic laser and single-mode vacuum squeezed light of 795 nm with periodically poled KTiOPO4 (PPKTP) crystals. We achieved 111 mW of ultra-violet (UV) light at 397.5 nm from 191 mW of fundamental light with a PPKTP crystal in a doubling cavity, corresponding to a conversion efficiency of 58.1%. Using the UV light to pump an optical parametric oscillator with a PPKTP crystal, we realized -5.6 dB of a maximum squeezing. We analyzed the pump power dependence of the squeezing level and concluded that the UV light induced losses limit the improvement of the squeezing level. The generated squeezed light has huge potential application in quantum memory and ultra-precise measurement. PMID- 26906811 TI - Four-wave mixing signal enhancement and optical bistability of a hybrid metal nanoparticle-quantum dot molecule in a nanomechanical resonator. AB - We investigate theoretically four-wave mixing (FWM) response and optical bistability (OB) in a hybrid nanosystem composed of a metal nanoparticle (MNP) and a semiconductor quantum dot (SQD) coupled to a nanomechanical resonator (NR). It is shown that the FWM signal is enhanced by more than three orders of magnitude as compared to that of the system without exciton-phonon interaction, and the FWM signal can also be suppressed significantly and broadened due to the exciton-plasmon interaction. As the MNP couples strongly with the SQD, the bistable FWM response can be achieved by adjusting the SQD-MNP distance and the pumping intensity. For a given pumping constant and a fixed SQD-MNP distance, the enhanced exciton-phonon interaction can promote the occurrence of bistability. Our findings not only present a feasible way to detect the spacing between two nanoparticles, but also hold promise for developing quantum switches and nanoscale rulers. PMID- 26906812 TI - Expansion of arbitrary electromagnetic fields in terms of vector spherical wave functions. AB - Since 1908, when Mie reported analytical expressions for the fields scattered by a spherical particle upon incidence of plane-waves, generalizing his analysis for the case of an arbitrary incident wave has been an open question because of the cancellation of the prefactor radial spherical Bessel function. This cancellation was obtained before by our own group for a highly focused beam centered in the objective. In this work, however, we show for the first time how these terms can be canceled out for any arbitrary incident field that satisfies Maxwells equations, and obtain analytical expressions for the beam shape coefficients. We show several examples on how to use our method to obtain analytical beam shape coefficients for: Bessel beams, general hollow waveguide modes and specific geometries such as cylindrical and rectangular. Our method uses the vector potential, which shows the interesting characteristic of being gauge invariant. These results are highly relevant for speeding up numerical calculation of light scattering applications such as the radiation forces acting on spherical particles placed in an arbitrary electromagnetic field, as in an optical tweezers system. PMID- 26906813 TI - Propagation dynamics of a wavepacket through an optical cavity. AB - We experimentally investigate propagation dynamics of a wavepacket through a high finesse optical cavity. Narrow-band and quasi-percussional excitations of a cavity field by a wavepacket are studied. When the spectral width of an incident wavepacket is narrowed compared with the cavity linewidth, the transmitted pulse is adiabatically followed the time evolution of the incoming pulse. For the quasi percussional excitation of very short pulse in time, the cavity is excited on the time duration of the incoming pulse. The falling edge of the wavepacket loses its original information and experiences a characteristic decay determined by the intracavity photon lifetime. The measured time delay of the pulse peak, in contrast to the constant delay predicted, greatly depends on the pulse width of the incoming wavepacket. We also examine the cavity high-reflected transient spike of optical precursors at the excitation of a step-modulated pulse. The experimental results show a very good agreement with a simple theoretical calculation. PMID- 26906814 TI - Symmetric signal and local oscillator polarization diverse coherent optical receiver. AB - An improved coherent optical receiver architecture that compensates for a random drift in the state of polarization (SOP) of both the signal and the local oscillator (LO) is presented for the first time. The proposed architecture comprises two conventional coherent optical receiver front-ends in tandem, where the SOP of the LO is first divided into its two orthogonal components and then distributed to each coherent optical receiver front-end module. Two distinct methods of polarization diversity recovery of the modulation based on the MRC technique and an eigenvalue-eigenvector decomposition of the covariance matrix have been used to effectively recover the transmitted signal. The concept is validated by numerical simulations, where a differential quadrature phase-shift keyed (DQPSK) modulated signal with a random time-varying SOP is first generated. After its mixing with a LO also possessing a random time-varying SOP, the algorithms that have been developed are provided with eight input variables to be digitally processed. The constellation diagrams corresponding to the recovered DQPSK modulation obtained using the two polarization diversity methods are presented. PMID- 26906815 TI - Tunable in-fiber Mach-Zehnder interferometer driven by unique acoustic transducer and its application in tunable multi-wavelength laser. AB - An in-fiber Mach-Zehnder interferometer was proposed and fabricated, which was based on a sandwich-like etched single mode fiber driven by only one acoustic transducer. It succeeded the feature of fast tuning and would not introduce frequency shift in the transmission spectrum. Based on it, a fast tuning dual wavelength laser with a two-wavelength spacing around 3.5 nm was proved with a tuning range of about 3.6 nm, covering wavelengths from 1561.6 nm to 1568.9 nm. PMID- 26906816 TI - Dual phase-shift Bragg grating silicon photonic modulator operating up to 60 Gb/s. AB - We demonstrate PAM-4 and OOK operation of a novel silicon photonic modulator. The modulator design is based on two phase-shifts in a Bragg Grating structure driven in a push pull configuration. Back-to-back PAM-4 modulation is demonstrated below the FEC threshold at up to 60 Gb/s. OOK modulation is also shown up to 55 Gb/s with MMSE equalization and up to 50 Gb/s without equalization. Eye diagrams and BER curves at different bit rates are provided for both PAM-4 and OOK modulations. To our knowledge, this structure is the fastest silicon photonic modulator based on Bragg gratings, reaching modulation speed comparable to the fastest Mach-Zehnder modulators and micro-ring modulators. PMID- 26906817 TI - Light localization and nonlinear beam transmission in specular amorphous photonic lattices. AB - We demonstrate specular photonic "lattices" with random index variations at disordered positions of lattice sites. These amorphous lattice structures, optically induced in a bulk nonlinear crystal, remain invariant during propagation since they are constructed from random components residing on a fixed ring in momentum space. We observe linear spatial localization of a light beam when probing through different "defect" points in such specular lattices, as well as the nonlinear destruction of localized modes. In addition, we illustrate the possibility of image transmission through the disordered lattices, when a self defocusing nonlinearity is employed. PMID- 26906818 TI - Influence of BaF2 and activator concentration on broadband near-infrared luminescence of Pr3+ ions in gallo-germanate glasses. AB - Thermal stability and broadband NIR luminescence of Pr(3+) doped gallo-germanate glasses with BaF2 have been studied. The thermal factors are larger for glass samples with low BaF2 content exhibiting good thermal stability against devitrification. Luminescence due to (1)D2 -> (1)G4 transition of Pr(3+) was measured under 450 nm excitation. The (1)D2 measured lifetimes depend critically on activator concentration, but remain nearly unchanged with BaF2 content. The emission linewidth, the emission cross-section, the figure of merit (FOM) and the sigmaem x FWHM product are relatively large, suggesting that Pr(3+)-doped gallo germanate glasses with presence of BaF2 are promising as gain media for broadband near-infrared amplifiers. PMID- 26906819 TI - Linearly dichroic plasmonic lens and hetero-chiral structures. AB - We present an experimental study of Hetero-Chiral (HC) plasmonic lenses, comprised of constituents with opposite chirality, demonstrating linearly dichroic focusing. The lenses focus only light with a specific linear polarization and result in a dark focal spot for the orthogonal polarization state. We introduce the design concepts and quantitatively compare several members of the HC family, deriving necessary conditions for linear dichroism and several comparative engineering parameters. The HC lenses were experimentally investigated using aperture-less near field scanning microscope collecting the amplitude of the plasmonic near-field. Our results exhibit an excellent match to the simulation predictions. The demonstrated ability for linearly dichroic functional focusing could lead to novel sensing applications. PMID- 26906820 TI - Spoof plasmon radiation using sinusoidally modulated corrugated reactance surfaces. AB - In this paper we theoretically investigate the feasibility of creating leaky wave antennas capable of converting spoof plasmons to radiating modes. Spoof plasmons are surface waves excited along metallic corrugated surfaces and they are considered the microwave and THz equivalent of optical surface plasmon polaritons. Given that a corrugated surface is essentially a reactance surface, the proposed design methodology relies on engineering a corrugated surface so that it exhibits a sinusoidally modulated reactance profile. Through such non uniform periodic reactance surfaces, guided surface waves can efficiently couple into free-space radiating modes. This requires the development of a realistic methodology that effectively maps the necessary sinusoidal reactance variation to a sinusoidal variation corresponding to the depth of the grooves. Both planar and cylindrical corrugated surfaces are examined and it is numerically demonstrated that the corresponding sinusoidally modulated leaky wave structures can very efficiently convert guided spoof plasmons to radiating modes. PMID- 26906821 TI - Reversibly tunable plasmonic bandgap by responsive hydrogel grating. AB - Reversible actuating of surface plasmon propagation by responsive hydrogel grating is reported. Thermo-responsive poly(N-isopropylacrylamide)-based (pNIPAAm) hydrogel nanostructure was designed and tethered to a gold surface in order to switch on and off Bragg scattering of surface plasmons which is associated with an occurrence of a bandgap in their dispersion relation. pNIPAAm based grating with a period around 280 nm was prepared by using photo crosslinkable terpolymer and laser interference lithography and it was brought in contact with water. The temperature induced swelling and collapse of pNIPAAm hydrogel grating strongly modulates its refractive index (Deltan~0.1) which leads to the reversible opening and closing of a plasmonic bandgap. The experiments demonstrate partial opening of a bandgap with the width of 12 nm at wavelength around 800 nm where SPR exhibited the spectral width of about 75 nm. PMID- 26906822 TI - Ultra-short FBG based distributed sensing using shifted optical Gaussian filters and microwave-network analysis. AB - Ultrashort fiber Bragg gratings (US-FBGs) have significant potential as weak grating sensors for distributed sensing, but the exploitation have been limited by their inherent broad spectra that are undesirable for most traditional wavelength measurements. To address this, we have recently introduced a new interrogation concept using shifted optical Gaussian filters (SOGF) which is well suitable for US-FBG measurements. Here, we apply it to demonstrate, for the first time, an US-FBG-based self-referencing distributed optical sensing technique, with the advantages of adjustable sensitivity and range, high-speed and wide range (potentially >14000 MUepsilon) intensity-based detection, and resistance to disturbance by nonuniform parameter distribution. The entire system is essentially based on a microwave network, which incorporates the SOGF with a fiber delay-line between the two arms. Differential detections of the cascaded US FBGs are performed individually in the network time-domain response which can be obtained by analyzing its complex frequency response. Experimental results are presented and discussed using eight cascaded US-FBGs. A comprehensive numerical analysis is also conducted to assess the system performance, which shows that the use of US-FBGs instead of conventional weak FBGs could significantly improve the power budget and capacity of the distributed sensing system while maintaining the crosstalk level and intensity decay rate, providing a promising route for future sensing applications. PMID- 26906823 TI - Highly sensitive multi-core flat fiber surface plasmon resonance refractive index sensor. AB - A simple multi-core flat fiber (MCFF) based surface plasmon resonance (SPR) sensor operating in telecommunication wavelengths is proposed for refractive index sensing. Chemically stable gold (Au) and titanium dioxide (TiO(2)) layers are used outside the fiber structure to realize a simple detection mechanism. The modeled sensor shows average wavelength interrogation sensitivity of 9,600 nm/RIU (Refractive Index Unit) and maximum sensitivity of 23,000 nm/RIU in the sensing range of 1.46-1.485 and 1.47-1.475, respectively. Moreover, the refractive index resolution of 4.35 * 10(-6) is demonstrated. Additionally, proposed sensor had shown the maximum amplitude interrogation sensitivity of 820 RIU(-1), with the sensor resolution of 1.22 * 10(-5) RIU. To the best of our knowledge, the proposed sensor achieved the highest wavelength interrogation sensitivity among the reported fiber based SPR sensors. Finally we anticipate that, this novel and highly sensitive MCFF SPR sensor will find the potential applications in real time remote sensing and monitoring, ultimately enabling inexpensive and accurate chemical and biochemical analytes detection. PMID- 26906824 TI - Dynamic creation of a light-induced terahertz guided-wave resonator. AB - We demonstrate a dynamic light-induced resonator for terahertz (THz) frequency light created on ultrashort time scales inside a planar waveguide. The resonator is created by patterned femtosecond photoexcitation of a one-dimensional array of photoconductive regions inside a silicon-filled parallel plate waveguide. The metal-dielectric photonic crystal is created on a 2 ps time scale, ten times faster than the 20 ps transit time of the THz light through the array. The resonance reveals itself through narrowband THz transmission enhancement with accompanying phase modulation producing an induced group delay of up to 10.8 ps near resonance. PMID- 26906825 TI - Phase retrieval of ultrashort laser pulses using a MIIPS algorithm. AB - We developed a new method for retrieving the group delay dispersion of a laser from Multiphoton Intra-pulse Interference Phase Scan (MIIPS) data. The method takes into account the spectral amplitude of the laser pulse and provides a direct feedback on the accuracy of the retrieval. The main advantage of the method derives from providing sufficiently high accuracy to avoid the need for multiple experimental iterations. Another advantage is that the new method can discriminate among pulses with different spectral phase and amplitude profiles, in which MIIPS traces occupy the same position in the phase-frequency MIIPS map. PMID- 26906826 TI - Multimode supercontinuum generation in chalcogenide glass fibres. AB - Mid-infrared supercontinuum generation is considered in chalcogenide fibres when taking into account both polarisations and the necessary higher order modes. In particular we focus on high pulse energy supercontinuum generation with long pump pulses. The modeling indicates that when only a single polarisation in the fundamental mode is considered the obtainable supercontinuum bandwidth is substantially exaggerated compared to when both polarisations are taken into account. Our modeling shows that if the pump pulse is short enough (<= 10 ps) then higher order modes are not important because of temporal walk-off. In contrast long pump pulses (>= 40 ps) will efficiently excite higher order modes through Raman scattering, which will deplete the fundamental mode of energy and limit the possibility of obtaining a broadband supercontinuum. PMID- 26906827 TI - Disposable photonic integrated circuits for evanescent wave sensors by ultra-high volume roll-to-roll method. AB - Flexible photonic integrated circuit technology is an emerging field expanding the usage possibilities of photonics, particularly in sensor applications, by enabling the realization of conformable devices and introduction of new alternative production methods. Here, we demonstrate that disposable polymeric photonic integrated circuit devices can be produced in lengths of hundreds of meters by ultra-high volume roll-to-roll methods on a flexible carrier. Attenuation properties of hundreds of individual devices were measured confirming that waveguides with good and repeatable performance were fabricated. We also demonstrate the applicability of the devices for the evanescent wave sensing of ambient refractive index. The production of integrated photonic devices using ultra-high volume fabrication, in a similar manner as paper is produced, may inherently expand methods of manufacturing low-cost disposable photonic integrated circuits for a wide range of sensor applications. PMID- 26906828 TI - Novel method for the measurement of liquid film thickness during fuel spray impingement on surfaces. AB - This paper describes the development and application of a novel optical technique for the measurement of liquid film thickness formed on surfaces during the impingement of automotive fuel sprays. The technique makes use of the change of the light scattering characteristics of a metal surface with known roughness, when liquid is deposited. Important advantages of the technique over previously established methods are the ability to measure the time-dependent spatial distribution of the liquid film without a need to add a fluorescent tracer to the liquid, while the measurement principle is not influenced by changes of the pressure and temperature of the liquid or the surrounding gas phase. Also, there is no need for non-fluorescing surrogate fuels. However, an in situ calibration of the dependence of signal intensity on liquid film thickness is required. The developed method can be applied to measure the time-dependent and two-dimensional distribution of the liquid fuel film thickness on the piston or the liner of gasoline direct injection (GDI) engines. The applicability of this technique was evaluated with impinging sprays of several linear alkanes and alcohols with different thermo-physical properties. The surface temperature of the impingement plate was controlled to simulate the range of piston surface temperatures inside a GDI engine. Two sets of liquid film thickness measurements were obtained. During the first set, the surface temperature of the plate was kept constant, while the spray of different fuels interacted with the surface. In the second set, the plate temperature was adjusted to match the boiling temperature of each fuel. In this way, the influence of the surface temperature on the liquid film created by the spray of different fuels and their evaporation characteristics could be demonstrated. PMID- 26906829 TI - Probing nonadiabatic molecular alignment by spectral modulation. AB - We investigated molecular alignment wakes of femtosecond laser pulses. Evolution of nonadiabatic molecular alignment in nitrogen gas has been measured via its nonlinear interaction effects with a variably delayed probe pulse. The induced rotational wave packet was mapped as a function of the angular difference between polarization directions of femtosecond pump and probe pulses as well as their relative delay and the plot of the variations of the rotational wave packet, i.e. "quantum carpet", was found to be in good agreement with the calculated angular and temporal dependencies of molecular alignment parameter. PMID- 26906830 TI - Suppression of infrared absorption in nanostructured metals by controlling Faraday inductance and electron path length. AB - Nanostructured metals have been intensively studied for optical applications over the past few decades. However, the intrinsic loss of metals has limited the optical performance of the metal nanostructures in diverse applications. In particular, light concentration in metals by surface plasmons or other resonances causes substantial absorption in metals. Here, we avoid plasmonic excitations for low loss and investigate methods to further suppress loss in nanostructured metals. We demonstrate that parasitic absorption in metal nanostructures can be significantly reduced over a broad band by increasing the Faraday inductance and the electron path length. For an example structure, the loss is reduced in comparison to flat films by more than an order of magnitude over most of the very broad spectrum between short and long wavelength infrared. For a photodetector structure, the fraction of absorption in the photoactive material increases by two orders of magnitude and the photoresponsivity increases by 15 times because of the selective suppression of metal absorption. These findings could benefit many metal-based applications that require low loss such as photovoltaics, photoconductive detectors, solar selective surfaces, infrared-transparent defrosting windows, and other metamaterials. PMID- 26906831 TI - Silicon carbide--a high-transparency nonlinear material for THz applications. AB - Optical properties of 4H-SiC were measured using time-domain and Fourier transform spectroscopy in the range of 0.1-20 THz. A high-transparency region was found between <0.1-10 THz. Based on the obtained data and published results, the refractive indices for o-wave and e-wave were approximated in the form of Sellmeier equations for the entire transparency range. Phase matched frequency conversion was found to be possible at wavelengths from the visible through the mid-IR and further into the far-IR (THz) region beyond 17 MUm. Extremely low absorption coefficient, high damage threshold, and the possibility of phase matching make this material highly suited for high power THz optics and generation. PMID- 26906832 TI - Nanosecond pulse shaping at 780 nm with fiber-based electro-optical modulators and a double-pass tapered amplifier. AB - We describe a system for generating frequency-chirped and amplitude-shaped pulses on time scales from sub-nanosecond to ten nanoseconds. The system starts with cw diode-laser light at 780 nm and utilizes fiber-based electro-optical phase and intensity modulators, driven by an arbitrary waveform generator, to generate the shaped pulses. These pulses are subsequently amplified to several hundred mW with a tapered amplifier in a delayed double-pass configuration. Frequency chirps up to 5 GHz in 2 ns and pulse widths as short as 0.15 ns have been realized. PMID- 26906833 TI - Background removal in soil analysis using laser- induced breakdown spectroscopy combined with standard addition method. AB - The matrix effect of powder samples, especially for soil samples, is significant in laser-induced breakdown spectroscopy (LIBS), which affects the prediction accuracy of the element concentration. In order to reduce this effect of the soil samples in LIBS, the standard addition method (SAM) based on background removal by wavelet transform algorithm was investigated in this work. Five different kinds of certified reference soil samples (lead (Pb) concentrations were 110, 283, 552, 675, and 1141 ppm, respectively) were used to examine the accuracy of this method. The root mean square error of prediction (RMSEP) was more than 303 ppm by using the conventional calibration method. After adoption of SAM with background removal by wavelet transform algorithm, the RMSEP was reduced to 25.7 ppm. Therefore, the accuracy of the Pb element was improved significantly. The mechanism of background removal by wavelet transform algorithm based on SAM is discussed. Further study demonstrated that this method can also improve the predicted accuracy of the Cd element. PMID- 26906834 TI - Secure polarization-independent subcarrier quantum key distribution in optical fiber channel using BB84 protocol with a strong reference. AB - A quantum key distribution system based on the subcarrier wave modulation method has been demonstrated which employs the BB84 protocol with a strong reference to generate secure bits at a rate of 16.5 kbit/s with an error of 0.5% over an optical channel of 10 dB loss, and 18 bits/s with an error of 0.75% over 25 dB of channel loss. To the best of our knowledge, these results represent the highest channel loss reported for secure quantum key distribution using the subcarrier wave approach. A passive unidirectional scheme has been used to compensate for the polarization dependence of the phase modulators in the receiver module, which resulted in a high visibility of 98.8%. The system is thus fully insensitive to polarization fluctuations and robust to environmental changes, making the approach promising for use in optical telecommunication networks. Further improvements in secure key rate and transmission distance can be achieved by implementing the decoy states protocol or by optimizing the mean photon number used in line with experimental parameters. PMID- 26906835 TI - Damage on fused silica optics caused by laser ablation of surface-bound microparticles. AB - High peak power laser systems are vulnerable to performance degradation due to particulate contamination on optical surfaces. In this work, we show using model contaminant particles that their optical properties decisively determine the nature of the optical damage. Borosilicate particles with low intrinsic optical absorption undergo ablation initiating in their sub-surface, leading to brittle fragmentation, distributed plasma formation, material dispersal and ultimately can lead to micro-fractures in the substrate optical surface. In contrast, energy coupling into metallic particles is highly localized near the particle-substrate interface leading to the formation of a confined plasma and subsequent etching of the substrate surface, accompanied by particle ejection driven by the recoil momentum of the ablation plume. While the tendency to create fractured surface pitting from borosilicate is stochastic, the smooth ablation pits created by metal particles is deterministic, with pit depths scaling linearly with laser fluence. A simple model is employed which predicts ~3x electric field intensity enhancement from surface-bound fragments. In addition, our results suggest that the amount of energy deposited in metal particles is at least twice that in transparent particles. PMID- 26906836 TI - Demostration of 520 Gb/s/lambda pre-equalized DFT-spread PDM-16QAM-OFDM signal transmission. AB - In this paper, we successfully transmit 8 * 520 Gb/s pre-equalized DFT-spread PDM 16QAM orthogonal frequency-division multiplexing (OFDM) signal over 840 km SMF with BER under 2.4 * 10(-2). We discuss how to obtain accurate tranceivers' response during pre-equalization for DFT-spread OFDM with coherent detection and we find conventional OFDM symbols training sequences (TSs) outperform DFT-spread OFDM symbols TSs in obtaining channel response for pre-equalization and equalization. Additionally, the optimal IFFT/FFT size is explored for the pre equalized DFT-spread PDM-16QAM-OFDM transmission systems. It is the first time to realize 400 Gb/s/lambda net rate OFDM signal transmission. PMID- 26906837 TI - Optically tunable microwave, millimeter-wave and submillimeter-wave utilizing single-mode Fabry-Perot laser diode subject to optical feedback. AB - In this paper, we use optical feedback injection technique to generate tunable microwave, millimeter-wave and submillimeter-wave signals using single-mode Fabry Perot laser diode. The beat frequency of the proposed generator ranges from 30.4 GHz to 3.40 THz. The peak power ratio between two resonating modes at the output spectrum of can be less than 0.5 dB by judiciously selecting feedback wavelength. In the stabilization test, the peak fluctuation of photonic signal is as low as 0.19 dB within half hour. Aside from locking regions, where the laser is easily locked by the injection beam, the side-mode suppression ratio is well over 25 dB with the maximum value of 36.6 dB at 30.4 GHz beat frequency. In addition, the minimum beat frequency interval between two adjacent photonic signals is as low as 10 GHz. PMID- 26906838 TI - Design of an ultrawide angle catadioptric lens with an annularly stitched aspherical surface. AB - We present an ultrawide angle catadioptric lens with a field of view (FOV) of 360 degrees * 270 degrees and F/# of 2.5. The lens consists of two optical configurations: the center configuration is all-refractive and has a FOV of +/- 50 degrees and the catadioptric configuration covers the remaining FOV. The MTF at 119lp/mm of the rear FOV (90 degrees to 135 degrees ) can be improved by 0.15 via applying an annularly stitched aspherical surface (ASAS) to the rear surface of the catadioptric element. The developed lens presents smaller marginal distortions and higher relative illuminations compared with traditional panoramic lenses. A proof-of-concept prototype producing acceptable image quality is developed. PMID- 26906839 TI - Influence of camera calibration conditions on the accuracy of 3D reconstruction. AB - For stereoscopic systems designed for metrology applications, the accuracy of camera calibration dictates the precision of the 3D reconstruction. In this paper, the impact of various calibration conditions on the reconstruction quality is studied using a virtual camera calibration technique and the design file of a commercially available lens. This technique enables the study of the statistical behavior of the reconstruction task in selected calibration conditions. The data show that the mean reprojection error should not always be used to evaluate the performance of the calibration process and that a low quality of feature detection does not always lead to a high mean reconstruction error. PMID- 26906840 TI - Slowing and stopping of wave in dispersive metamaterial loaded helical guide. AB - We propose a dispersive metamaterial loaded helical waveguide (DMLHG) structure that supports slowing and stopping of Electromagnetic (EM) wave. Analytical and computational characterizations have been done to visualize various modal characteristics in detail using the Drude model as a dispersive parameter. It is observed that metamaterial insertion enhances helical guide slow wave behaviour and it supports both forward wave (FW) and backward wave (BW) as well as mode degeneracy. Obtained mode degeneracy mechanism leads to trapping of EM wave. The proposed guide structure provides a dynamic control of wave velocity by varying its physical parameters. Two possible structures are designed and simulated using CST Microwave Studio Software. The simulation results verify the presence of similar characteristics as observed in analytical study such as FW, BW, mode degeneracy, but in slightly shifted frequency spectrum. PMID- 26906841 TI - 40 Gb/s reconfigurable optical logic gates based on FWM in silicon waveguide. AB - Here we experimentally demonstrate reconfigurable logic gates via four-wave mixing (FWM) in silicon waveguide with an operating speed of up to 40 Gb/s. After demodulated by a 40-GHz delay interferometer (DI), four non-return-to-zero differential phase shift keying (NRZ-DPSK) signals with carefully selected wavelengths are launched into the waveguide at the same time. Thanks to the effective FWM in silicon nano-waveguide, a full set of the two-input logic minterms can be generated simultaneously, and arbitrary combinational logic functions are able to be realized by properly combining these minterms. PMID- 26906842 TI - Modelling parametric down-conversion yielding spectrally pure photon pairs. AB - Pair creation by spontaneous parametric down-conversion (SPDC) has become a reliable source for single-photon states, used in many kinds of quantum information experiments and applications. In order to be spectrally pure, the two photons within a generated pair should be as frequency-uncorrelated as possible. For this purpose most experiments use narrow bandpass filters, having to put up with a drastic decrease in count rates. This article elaborates (theoretically and by numerical evaluation) the alternative method to engineer a setup such that the SPDC-generated quantum states are intrinsically pure. Using pulsed pump lasers and periodically poled crystals this approach makes bandpass filtering obsolete and allows for significantly higher output intensities and therefore count rates in the detectors. After numerically scanning all common wavelength regimes, polarisation configurations and three different non-linear crystals, we present a broad variety of setups which allow for an implementation of this method. PMID- 26906843 TI - Near-field terahertz imaging using sub-wavelength apertures without cutoff. AB - We demonstrate near-field imaging capabilities of a conical waveguide without cutoff using broadband terahertz (THz) radiation. In contrast to conventional conically tapered waveguides, which are characterized by strong suppression of transmission below the cutoff frequency, the proposed structure consists of two pieces, such that there is an adjustable gap along the length of the waveguide. We also ensure that the sidewalls are thin in the vicinity of the gap. The combination of these geometrical features allow for significantly enhanced transmission at frequencies below the cutoff frequency, without compromising the mode confinement and, consequently, the spatial resolution when used for imaging applications. We demonstrate near-field imaging with this probe simultaneously at several frequencies, corresponding to three regimes: above, near and below the cutoff frequency. We observe only mild degradation in the image quality as the frequency is reduced below the cutoff frequency. These results suggest that further refinements in the probe structure will allow for improved imaging capabilities at frequencies well below the cutoff frequency. PMID- 26906844 TI - 295 mW output, frequency-stabilized erbium silica fiber laser with a linewidth of 5 kHz and a RIN of -120 dB/Hz. AB - We demonstrate the frequency stabilization of a high output power, erbium silica fiber laser by utilizing a (13)C2H2 (acetylene) absorption line at 1538.8 nm and a H(13)C(14)N (hydrogen cyanide) absorption line at 1549.73 nm. We introduced a novel short ring cavity configuration and pump power feedback control to suppress the intensity noise of the laser output, which is caused by the relaxation oscillation of erbium ions. As a result, we succeeded in simultaneously obtaining a stable single-frequency oscillation with an output power of over 290 mW, a linewidth of 5 kHz, and a low relative intensity noise (RIN) of -120 dB/Hz. The frequency stabilities reached 2.8 * 10(-11) and 6.9 * 10(-11) for an integration time of 1 s with a (13)C2H2 and a H(13)C(14)N absorption line, respectively. PMID- 26906845 TI - Energy efficiency of optical grooming of QAM optical transmission channels. AB - Analysis of the energy use for optical grooming of quadrature amplitude modulated signals in optical transmission systems is used to determine the potential efficiency benefits. An energy model is developed for both optical and electronic grooming and used to study the relative efficiency for three different network scenarios. The energy efficiency is evaluated considering both coherent and direct detection transceivers including power management strategies. Results indicate efficiency improvements up to an order of magnitude may be possible for 100 GBaud rates and 25-30 GBaud is a critical point at which optical grooming becomes the more efficient approach. These results are further shown to apply for the case of projected efficiency improvements in the underlying device technologies. PMID- 26906846 TI - Sensing interrogation technique for fiber-optic interferometer type of sensors based on a single-passband RF filter. AB - In this paper, a sensing interrogation system for fiber-optic interferometer type of sensors by using a single-passband radio-frequency (RF) filter has been proposed and experimentally demonstrated. The fiber-optic interferometer based sensors can give continuous optical sampling, and along with dispersive medium a single-passband RF frequency response can be achieved. The sensing parameter variation on the fiber-optic interferometer type of sensors will affect their free spectrum range, and thus the peak frequency of the RF filter. By tracking the central frequency of the passband the sensing parameter can be demodulated. As a demonstration, in our experiment a fiber Mach-Zehnder interferometer (FMZI) based temperature sensor has been interrogated. By tracking the peak frequency of the passband the temperature variation can be monitored. In our experiment, the sensing responsivity of 10.5 MHz/ degrees C, 20.0 MHz/ degrees C and 41.2 MHz/ degrees C, when the lengths of sensing fiber are 1 m, 2 m and 4 m have been achieved. PMID- 26906847 TI - Optimisation of amplitude limiters for phase preservation based on the exact solution to degenerate four-wave mixing. AB - Adopting an exact solution to four-wave mixing (FWM), wherein harmonic evolution is described by the sum of two Bessel functions, we identify two causes of amplitude to phase noise conversion which impair FWM saturation based amplitude regenerators: self-phase modulation (SPM) and Bessel-order mixing (BOM). By increasing the pump to signal power ratio, we may arbitrarily reduce their impact, realising a phase preserving amplitude regenerator. We demonstrate the technique by applying it to the regeneration of a 10 GBaud QPSK signal, achieving a high level of amplitude squeezing with minimal amplitude to phase noise conversion. PMID- 26906848 TI - Ultra-sensitive angle sensor based on laser autocollimation for measurement of stage tilt motions. AB - An ultra-sensitive angle sensor employing single-cell photodiodes, which allows tighter focusing leading to a higher angular resolution better than 0.001 arc second, has been designed based on laser autocollimation. Aiming to investigate the influences of spherical aberrations in the optical system on the sensor sensitivity, an optical model has been established based on wave optics. Computer simulation has been carried out by using the model, and its feasibility has been verified in experiments. In addition, a prototype optical angle sensor has been designed in a compact size of 100 mm * 150 mm, and its measurement resolution has been verified in experiments. PMID- 26906849 TI - Photonic crystal fiber in-line Mach-Zehnder interferometer for explosive detection. AB - We report a photonic crystal fiber (PCF) in-line Mach-Zehnder interferometer used as a gas sensor device which exhibits high sensitivity to the explosive trinitrotoluene (TNT). The interferometric sensor head is formed by embedding a segment of large-mode-area/grapefruit PCF between standard single-mode fibers via butt coupling, which produces two small air gaps in between terminated fiber ends with ceramic ferrule connectors as coupling regions, which also serve as inlet/outlet for the gas. The spectral response of the interferometer is investigated in terms of its wavelength spectrum. The selectivity to TNT vapor is achieved by immobilizing a molecular recognition ployallylamine layer on the inner surface of the holey region of the PCF. The TNT-induced variations of the interference fringes are measured and the sensing capability of the proposed sensor is demonstrated experimentally. PMID- 26906850 TI - Probability of the residual wavefront variance of an adaptive optics system and its application. AB - For performance evaluation of an adaptive optics (AO) system, the probability of the system residual wavefront variance can provide more information than the wavefront variance average. By studying the Zernike coefficients of an AO system residual wavefront, we derived the exact expressions for the probability density functions of the wavefront variance and the Strehl ratio, for instantaneous and long-term exposures owing to the insufficient control loop bandwidth of the AO system. Our calculations agree with the residual wavefront data of a closed loop AO system. Using these functions, we investigated the relationship between the AO system bandwidth and the distribution of the residual wavefront variance. Additionally, we analyzed the availability of an AO system for evaluating the AO performance. These results will assist in designing and probabilistic analysis of AO systems. PMID- 26906851 TI - Superbroad visible to NIR photoluminescence from Bi+ evidenced in Ba2B5O9Cl: Bi crystal. AB - The nature of bismuth NIR luminescence is essential to develop the bismuth doped laser materials with high efficiency and desirable emission wavelength, and it, thereby, receives rising interests. Our previous work reported the Bi(0) luminescence from Ba2B5O9Cl: Bi with a lifetime of ~30 MUs and the conversion of Bi(2+) to Bi(0). This work found indeed the conversion could be enabled in the compound by an in situ reduction technique and it, however, happens via an intermediate state of Bi(+). Once the ion of Bi(+) is stabilized and built into the compound, it can luminesce in a super broad spectral range from 600 to 1200 nm with a lifetime longer than 1 ms, due to the cascade transitions from (3)P2 and (3)P1 to (3)P0. This is completely different from Bi(0) and Bi(2+) in the compound, and it has never been noticed before. We believe this work can help us better understand the complex nature of bismuth luminescence. PMID- 26906852 TI - On-chip generation of photon-triplet states. AB - Efficient sources of many-partite non-classical states are key for the advancement of quantum technologies and for the fundamental testing of quantum mechanics. We demonstrate the generation of time-correlated photon triplets at telecom wavelengths via pulsed cascaded parametric down-conversion in a monolithically integrated source. By detecting the generated states with success probabilities of (6.25 +/- 1.09) * 10(-11) per pump pulse at injected powers as low as 10 MUW, we benchmark the efficiency of the complete system and deduce its high potential for scalability. Our source is unprecedentedly long-term stable, it overcomes interface losses intrinsically due to its monolithic architecture, and the photon-triplet states dominate uncorrelated noise significantly. These results mark crucial progress towards the proliferation of robust, scalable, synchronized and miniaturized quantum technology. PMID- 26906853 TI - Regular oscillations and random motion of glass microspheres levitated by a single optical beam in air. AB - We experimentally report on optical binding of many glass particles in air that levitate in a single optical beam. A diversity of particle sizes and shapes interact at long range in a single Gaussian beam. Our system dynamics span from oscillatory to random and dimensionality ranges from 1 to 3D. The low loss for the center of mass motion of the beads could allow this system to serve as a standard many body testbed, similar to what is done today with atoms, but at the mesoscopic scale. PMID- 26906854 TI - Q-switched waveguide laser based on two-dimensional semiconducting materials: tungsten disulfide and black phosphorous. AB - Owing to their unique properties, graphene-like two dimensional semiconducting materials, including Tungsten Disulfide (WS2) and Black Phosphorous (BP), have attracted increasing interest from basic research to practical applications. Herein, we demonstrated the ultrafast nonlinear saturable absorption response of WS2 and BP films in the waveguide structure. Through fabricating WS2 and BP films by evaporating the solutions on glass wafers. Saturable absorber films were attached onto the end-facet of the waveguide, which therefore constitutes a resonant cavity for the waveguide laser. Under a pump laser at 810 nm, we could obtain a stable Q-switched operation in the waveguide structure. This work indicated the significant potential of WS2 and BP for the ultrafast waveguide laser. PMID- 26906855 TI - Wave coupling theory of nonlocal linear electro-optic effect. AB - We derive a wave coupling theory of nonlocal linear electro-optic effect, and the analytical solutions of the resultant equations are provided. With the solutions we study the nonlocal linear electro-optic effect in crystals of different symmetry groups. It shows that the nonlocality of chi(2) plays a non-negligible role on the linear electro-optic effect only when the nonlocal characteristic length of chi(2) is comparable with the beam width, and the output beam is no longer Gaussian shape as the input beam in an electro-optic amplitude modulation when nonlocality of chi(2) is non-negligible. Methods to measure the nonlocal characteristic lengths of of chi(1) and chi(2) are also discussed. PMID- 26906856 TI - Size-dependent two-photon absorption in circular graphene quantum dots. AB - We investigate theoretically the size-dependence of two-photon absorption (TPA) for circular graphene quantum dots (GQDs) on the basis of electronic energy states obtained by solving the Dirac-Weyl equation analytically under infinite mass boundary condition. The analytical expressions for TPA coefficient are derived with an arbitrary size-distribution and the transition selection rules are obtained. Results reveal that the intraband transitions in conduction band and valence band contribute much more to TPA than interband transitions. The energy spectrum and TPA peaks are tuned by the size of GQDs. PMID- 26906857 TI - Complex master slave interferometry. AB - A general theoretical model is developed to improve the novel Spectral Domain Interferometry method denoted as Master/Slave (MS) Interferometry. In this model, two functions, g and h are introduced to describe the modulation chirp of the channeled spectrum signal due to nonlinearities in the decoding process from wavenumber to time and due to dispersion in the interferometer. The utilization of these two functions brings two major improvements to previous implementations of the MS method. A first improvement consists in reducing the number of channeled spectra necessary to be collected at Master stage. In previous MSI implementation, the number of channeled spectra at the Master stage equated the number of depths where information was selected from at the Slave stage. The paper demonstrates that two experimental channeled spectra only acquired at Master stage suffice to produce A-scans from any number of resolved depths at the Slave stage. A second improvement is the utilization of complex signal processing. Previous MSI implementations discarded the phase. Complex processing of the electrical signal determined by the channeled spectrum allows phase processing that opens several novel avenues. A first consequence of such signal processing is reduction in the random component of the phase without affecting the axial resolution. In previous MSI implementations, phase instabilities were reduced by an average over the wavenumber that led to reduction in the axial resolution. PMID- 26906858 TI - Maximum and minimum amplitudes of the moire patterns in one- and two-dimensional binary gratings in relation to the opening ratio. AB - The amplitude of the moire patterns is estimated in relation to the opening ratio in line gratings and square grids. The theory is developed; the experimental measurements are performed. The minimum and the maximum of the amplitude are found. There is a good agreement between the theoretical and experimental data. This is additionally confirmed by the visual observation. The results can be applied to the image quality improvement in autostereoscopic 3D displays, to the measurements, and to the moire displays. PMID- 26906859 TI - Measurement and limitations of optical orbital angular momentum through corrected atmospheric turbulence. AB - In recent years, there have been a series of proposals to exploit the orbital angular momentum (OAM) of light for astronomical applications. The OAM of light potentially represents a new way in which to probe the universe. The study of this property of light entails the development of new instrumentation and problems which must be addressed. One of the key issues is whether we can overcome the loss of the information carried by OAM due to atmospheric turbulence. We experimentally analyze the effect of atmospheric turbulence on the OAM content of a signal over a range of realistic turbulence strengths typical for astronomical observations. With an adaptive optics system we are able to recover up to 89% power in an initial non-zero OAM mode (l = 1) at low turbulence strengths (0.30" FWHM seeing). However, for poorer seeing conditions (1.1" FWHM seeing), the amount of power recovered is significantly lower (5%), showing that for the terrestrial detection of astronomical OAM, a careful design of the adaptive optics system is needed. PMID- 26906860 TI - Zoom microscope objective using electrowetting lenses. AB - We report a zoom microscope objective which can achieve continuous zoom change and correct the aberrations dynamically. The objective consists of three electrowetting liquid lenses and two glass lenses. The magnification is changed by applying voltages on the three electrowetting lenses. Besides, the three electrowetting liquid lenses can play a role to correct the aberrations. A digital microscope based on the proposed objective is demonstrated. We analyzed the properties of the proposed objective. In contrast to the conventional objectives, the proposed objective can be tuned from ~7.8 * to ~13.2 * continuously. For our objective, the working distance is fixed, which means no movement parts are needed to refocus or change its magnification. Moreover, the zoom objective can be dynamically optimized for a wide range of wavelength. Using such an objective, the fabrication tolerance of the optical system is larger than that of a conventional system, which can decrease the fabrication cost. The proposed zoom microscope objective cannot only take place of the conventional objective, but also has potential application in the 3D microscopy. PMID- 26906861 TI - Polarization-entangled photon-pair source obtained via type-II non-collinear SPDC process with PPKTP crystal. AB - We demonstrate a polarization-entangled photon-pair source obtained via a type-II non-collinear quasi-phase-matched spontaneous parametric down-conversion process with a 10-mm periodically poled KTiOPO4 crystal, which is as stable and wavelength-tunable as the well-known Sagnac configuration scheme. A brightness of 4.2 kHz/mW is detected and a concurrence of 0.975 is estimated using quantum state tomography. Without loss of entanglement and brightness, the photon-pair wavelengths are tunable through control of the crystal temperature. This improvement is achieved using the non-collinear configuration and a stable interferometric distinguishability compensator. PMID- 26906862 TI - Photonic crystal micropost as a microarray platform. AB - This study demonstrates a photonic crystal micropost (PCMP) substrate for microarray applications. The substrate comprises an array of circular MPs with a PC on top of these MPs. This substrate enables biomolecule-containing droplets to form a composite contact upon deposition, thus allowing biomolecules to be attached on only the MPs, forming spots. When the device (PC) is excited on resonance, the electric field intensity is enhanced on only the top surface of the MPs. This enables the fluorescence intensities to be enhanced up to 5.50x; principally, this enhancement does not engender an increase in the background (intensity outside MP or spots) and noise intensities. The PCMP substrate enhances the spot intensity and minimizes the background intensity, enabling the detection of lower concentration analytes. PMID- 26906863 TI - Optical characterization of directly deposited graphene on a dielectric substrate. AB - By using scanning multiphoton microscopy we compare the nonlinear optical properties of the directly deposited and transferred to the dielectric substrate graphene. The direct deposition of graphene on oxidized silicon wafer was done by utilizing sacrificial copper catalyst film. We demonstrate that the directly deposited graphene and bi-layered transferred graphene produce comparable third harmonic signals and have almost the same damage thresholds. Therefore, we believe directly deposited graphene is suitable for the use of e.g. nanofabricated optical setups. PMID- 26906864 TI - Towards quantification of the crucial impact of auger recombination for the efficiency droop in (AlInGa)N quantum well structures. AB - Recent experimental investigations on the reduction of internal quantum efficiency with increasing current density in (AlInGa)N quantum well structures show that Auger recombination is a significant contributor to the so-called "droop" phenomenon. Using photoluminescence (PL) test structures, we find Auger processes are responsible for at least 15 % of the measured efficiency droop. Furthermore, we confirm that electron-electron-hole (nnp) is stronger than electron-hole-hole (npp) Auger recombination in standard LEDs. The ratio of respective Auger coefficients is determined to be in the range 1 < Cnnp/Cnpp <= 12. This asymmetry is shown to limit the detection efficiency of Auger processes in our PL-based approach. PMID- 26906865 TI - Compact gas cell integrated with a linear variable optical filter. AB - A miniaturized methane (CH(4)) sensor based on nondispersive infrared absorption is realized in MEMS technology. A high level of functional integration is achieved by using the resonance cavity of a linear variable optical filter (LVOF) also as a gas absorption cell. For effective detection of methane at lambda = 3.39 um, an absorption path length of at least 5 mm is required. Miniaturization therefore necessitates the use of highly reflective mirrors and operation at the 15th-order mode with a resonator cavity length of 25.4 um. The conventional description of the LVOF in terms of the Fabry-Perot resonator is inadequate for analyzing the optical performance at such demanding boundary conditions. We demonstrate that an approach employing the Fizeau resonator is more appropriate. Furthermore, the design and fabrication in a CMOS-compatible microfabrication technology are described and operation as a methane sensor is demonstrated. PMID- 26906866 TI - Frequency resolved cross-correlation between optical and terahertz pulses: application to ultrashort laser pulse characterization. AB - We have analyzed both theoretically and experimentally the spectrum of the optical pulses produced by the interaction of optical and THz pulses in a ZnTe crystal. Recorded as a function of the delay between the two pulses, the resulting spectrogram can be viewed as a frequency resolved cross-correlation between the optical and THz pulses making it possible to characterize the optical pulse. PMID- 26906867 TI - Optimized design of N optical filters for color and polarization imaging. AB - Designs of N optical filters for color and polarization imaging are found by minimizing detector noise, photon shot noise, and interpolation error for the image acquisition in a division of focal plane configuration. To minimize interpolation error, a general tiling procedure and an optimized tiling pattern for N filters are presented. For multispectral imaging, a general technique to find the transmission band is presented. For full Stokes polarization imaging, the general design with optimized retardances and fast angles of the polarizers is compared with the solution of the Thomson problem. These results are applied to the design of a three-color full Stokes imaging camera. PMID- 26906868 TI - Unveiling the photonic spin Hall effect with asymmetric spin-dependent splitting. AB - The photonic spin Hall effect (SHE) manifests itself as the spin-dependent splitting of light beam. Usually, it shows a symmetric spin-dependent splitting, i.e., the left- and right-handed circularly polarized components are equally separated in position and intensity for linear polarization incidence. In this paper, we theoretically propose an asymmetric spin-dependent splitting at an air glass interface under the illumination of elliptical polarization beam and experimentally demonstrate it with the weak measurement method. The left- and right-handed circularly polarized components show expectedly unequal intensity distributions and unexpectedly different spin-dependent shifts. Remarkably, the asymmetric spin-dependent splitting can be modulated by adjusting the handedness of incident polarization. The inherent physics behind this interesting phenomenon is attributed to the additional spatial Imbert-Fedorov shift. These findings offer us potential methods for developing new spin-based nanophotonic applications. PMID- 26906869 TI - Enhanced SOFI algorithm achieved with modified optical fluctuating signal extraction. AB - In this paper, we present a modified SOFI algorithm with enhanced temporal resolution: the required number of raw images for SOFI is reduced from hundreds to tens. The modification is intended to eliminate the low-frequency fluctuation and readout noise from the raw image stack, and is achieved by separately utilizing two wavelet-based filters in the temporal and spatial domains of the raw image stack. The high-frequency stochastic fluctuating signal could be extracted effectively, and the efficiency of SOFI could be enhanced. The modified SOFI image could be generated with 25 frames of raw images, and the corresponding acquisition time was 1.25 s. PMID- 26906870 TI - Gain dependent pulse regimes transitions in a dissipative dispersion-managed fibre laser. AB - For the first time, we demonstrate the possibility to switch between three distinct pulse regimes in a dissipative dispersion-managed (DM) fibre laser by solely controlling the gain saturation energy. Nonlinear Schrodinger equation based simulations show the transitions between hyper-Gaussian similaritons, parabolic similaritons, and dissipative solitons in the same laser cavity. It is also shown that such transitions exist in a wide dispersion range from all-normal to slightly net-normal dispersion. This work demonstrates that besides dispersion and filter managements gain saturation energy can be a new degree of freedom to manage pulse regimes in DM fibre lasers, which offers flexibility in designing ultrafast fibre lasers. Also, the result indicates that in contrast to conservative soliton lasers whose intensity profiles are unique, dissipative DM lasers show diversity in pulse shapes. The findings not only give a better understanding of pulse shaping mechanisms in mode-locked lasers, but also provide insight into dissipative systems. PMID- 26906871 TI - Physical insights of cavity confinement enhancing effect in laser-induced breakdown spectroscopy. AB - Using cavity confinement to enhance the plasma emission has been proved to be an effective way in LIBS technique while no direct visual evidence has been made to illustrate the physical mechanism of this enhancing effect. In this work, both laser-induced plasma plume images and shockwave images were obtained and synchronized for both flat surface case and rectangular cavity case. Phenomena of shockwave reflection, plasma compression by the reflected shockwave and merge of the reflected shockwave into plasma were observed. Plasma emission intensities recorded by ICCD in both cases were compared and the enhancement effect in the cavity case was identified in the comparison. The enhancement effect could be explained as reflected shockwave "compressing" effect, that is, the reflected shockwave would compress the plasma and result in a more condensed plasma core area with higher plasma temperature. Reflected shockwave also possibly contributed to plasma core position stabilization, which indicated the potential of better plasma signal reproducibility for the cavity case. Both plasma emission enhancement and plasma core position stabilization only exist within a certain temporal window, which indicates that the delay time of spectra acquisition is essential while using cavity confinement as a way to improve LIBS performance. PMID- 26906872 TI - Optimization of light field display-camera configuration based on display properties in spectral domain. AB - The visualization capability of a light field display is uniquely determined by its angular and spatial resolution referred to as display passband. In this paper we use a multidimensional sampling model for describing the display-camera channel. Based on the model, for a given display passband, we propose a methodology for determining the optimal distribution of ray generators in a projection-based light field display. We also discuss the required camera setup that can provide data with the necessary amount of details for such display that maximizes the visual quality and minimizes the amount of data. PMID- 26906873 TI - Generation, guiding and splitting of triggered single photons from a resonantly excited quantum dot in a photonic circuit. AB - We demonstrate resonance fluorescence from single In-GaAs/GaAs quantum dots embedded in a rib waveguide beamsplitter structure operated under pulsed laser excitation. A systematic study on the excitation laser pulse duration depicts that a sufficiently small laser linewidth enables a substantial improved single photon-to-laser-background ratio inside a waveguide chip. This manifests in the observation of clear Rabi oscillations over two periods of the quantum dot emission as a function of laser excitation power. A photon cross-correlation measurement between the two output arms of an on-chip beamsplitter results in a g(2)(0)=0.18, demonstrating the generation, guiding and splitting of triggered single photons under resonant excitation in an on-chip device. The present results open new perspectives for the implementation of photonic quantum circuits with integrated quantum dots as resonantly-pumped deterministic single-photon sources. PMID- 26906874 TI - All polarization-maintaining Er fiber-based optical frequency combs with nonlinear amplifying loop mirror. AB - A fully stabilized all polarization-maintaining Er frequency comb with a nonlinear amplifying loop mirror with below 0.2 rad carrier-envelope-offset frequency phase noise is demonstrated. The integrated timing jitter is measured as 40 attosecond from 10 kHz to 10 MHz, which is the lowest value of any Er fiber frequency comb to date. PMID- 26906875 TI - CEO stabilized frequency comb from a 1-MUm Kerr-lens mode-locked bulk Yb:CYA laser. AB - We report the first Kerr-lens mode-locked (KLM) bulk frequency comb in the 1-MUm spectral regime. The fundamental KLM Yb:CYA laser is pumped by a low-noise, high bright 976-nm fiber laser and typically provides 250-mW output power and 57-fs pulse duration. Only 58-mW output pulses were launched into a 1.3-m photonic crystal fiber (PCF) for one octave-spanning supercontinuum generation. Using a simplified collinear f-2f interferometer, the free-running carrier-envelope offset (CEO) frequency was measured to be 42-dB signal-to-noise ratio (SNR) for a 100-kHz resolution and 9.6-kHz full width at half maximum (FWHM) under a 100-Hz resolution. A long-term CEO control at 23 MHz was ultimately realized by feeding the phase error signal to the pump power of the oscillator. The integrated phase noise (IPN) of the locked CEO was measured to be 316 mrad with an integrated range from 1 Hz to 10 MHz. The standard deviation and Allan deviation for more than 4-hour recording are 1.6 mHz and 5.6 * 10(-18) (for 1-s gate time), respectively. This is, to the best of our knowledge, the best stability achieved among the 1-MUm solid-state frequency combs. PMID- 26906876 TI - Morphological appearances and photo-controllable coloration of dye-doped cholesteric liquid crystal/polymer coaxial microfibers fabricated by coaxial electrospinning technique. AB - This study systematically investigates the morphological appearance of azo-chiral dye-doped cholesteric liquid crystal (DDCLC)/polymer coaxial microfibers obtained through the coaxial electrospinning technique and examines, for the first time, their photocontrollable reflection characteristics. Experimental results show that the quasi-continuous electrospun microfibers can be successfully fabricated at a high polymer concentration of 17.5 wt% and an optimum ratio of 2 for the feeding rates of sheath to core materials at 25 degrees C and a high humidity of 50% +/- 2% in the spinning chamber. Furthermore, the optical controllability of the reflective features for the electrospun fibers is studied in detail by changing the concentration of the azo-chiral dopant in the core material, the UV irradiation intensity, and the core diameter of the fibers. Relevant mechanisms are addressed to explain the optical-control behaviors of the DDCLC coaxial fibers. Considering the results, optically controllable DDCLC coaxial microfibers present potential applications in UV microsensors and wearable smart textiles or swabs. PMID- 26906877 TI - Optical measurement of the temporal delay between two ultra-short and focussed laser pluses. AB - Temporal overlapping of ultra-short and focussed laser pulses is a particularly challenging task, as this timescale lies orders of magnitude below the typical range of fast electronic devices. Here we present an optical technique that allows for the measurement of the temporal delay between two focussed and ultra short laser pulses. This method is virtually applicable to any focussing geometry and relative intensity of the two lasers. Experimental implementation of this technique provides excellent quantitative agreement with theoretical expectations. The proposed technique will prove highly beneficial for high-power multiple-beam laser experiments. PMID- 26906878 TI - Respiratory syncytial virus - more chimera than chimpanzee? PMID- 26906880 TI - Editorial. PMID- 26906879 TI - Sizing and Discovery of Nanosized Polyoxometalate Clusters by Mass Spectrometry. AB - Ion mobility-mass spectrometry (IM-MS) is a powerful technique for structural characterization, e.g., sizing and conformation, particularly when combined with quantitative modeling and comparison to theoretical values. Traveling wave IM-MS (TW-IM-MS) has recently become commercially available to nonspecialist groups and has been exploited in the structural study of large biomolecules, however reliable calibrants for large anions have not been available. Polyoxometalate (POM) species-nanoscale inorganic anions-share many of the facets of large biomolecules, however, the full potential of IM-MS in their study has yet to be realized due to a lack of suitable calibration data or validated theoretical models. Herein we address these limitations by reporting DT-IM (drift tube) data for a set of POM clusters {M12} Keggin 1, {M18} Dawson 2, and two {M7} Anderson derivatives 3 and 4 which demonstrate their use as a TW-IM-MS calibrant set to facilitate characterization of very large (ca. 1-4 nm) anionic species. The data was also used to assess the validity of standard techniques to model the collision cross sections of large inorganic anions using the nanoscale family of compounds based upon the {Se2W29} unit including the trimer, {Se8W86O299} A, tetramer, {Se8W116O408} B, and hexamer {Se12W174O612} C, including their relative sizing in solution. Furthermore, using this data set, we demonstrated how IM-MS can be used to conveniently characterize and identify the synthesis of two new, i.e., previously unreported POM species, {P8W116}, unknown D, and {Te8W116}, unknown E, which are not amenable to analysis by other means with the approximate formulation of [H34W118X8M2O416](44-), where X = P and M = Co for D and X = Te and M = Mn for E. This work establishes a new type of inorganic calibrant for IM MS allowing sizing, structural analysis, and discovery of molecular nanostructures directly from solution. PMID- 26906881 TI - Fear of large carnivores causes a trophic cascade. AB - The fear large carnivores inspire, independent of their direct killing of prey, may itself cause cascading effects down food webs potentially critical for conserving ecosystem function, particularly by affecting large herbivores and mesocarnivores. However, the evidence of this has been repeatedly challenged because it remains experimentally untested. Here we show that experimentally manipulating fear itself in free-living mesocarnivore (raccoon) populations using month-long playbacks of large carnivore vocalizations caused just such cascading effects, reducing mesocarnivore foraging to the benefit of the mesocarnivore's prey, which in turn affected a competitor and prey of the mesocarnivore's prey. We further report that by experimentally restoring the fear of large carnivores in our study system, where most large carnivores have been extirpated, we succeeded in reversing this mesocarnivore's impacts. We suggest that our results reinforce the need to conserve large carnivores given the significant "ecosystem service" the fear of them provides. PMID- 26906882 TI - A nematode microtubule-associated protein, PTL-1, closely resembles its mammalian counterparts in overall molecular architecture. AB - The mammalian microtubule-associated proteins (MAPs), MAP2, MAP4, and tau, are structurally similar and considered to be evolutionarily related. The primary structure of a nematode MAP, PTL-1, also reportedly resembles those of the MAPs, but only in a small portion of the molecule. In this study, we elucidated the overall domain organization of PTL-1, using a molecular dissection technique. Firstly, we isolated nematode microtubules and proved that the recombinant PTL-1 binds to nematode and porcine microtubules with similar affinities. Then, the recombinant PTL-1 was genetically dissected to generate four shorter polypeptides, and their microtubule-binding and assembly promoting activities were assessed, using porcine microtubules and tubulin. PTL-1 was found to consist of two parts, microtubule-binding and projection domains, with the former further divided into three functionally distinct subdomains. The molecular architecture of PTL-1 was proved to be quite analogous to its mammalian counterparts, MAP2, MAP4, and tau, strongly supporting their evolutionary relationships. PMID- 26906883 TI - [Doctors focus on the needs of the elderly]. AB - The Dutch National Care for the Elderly Programme started in 2008. Eight regional networks were formed, in which more than 75 projects were carried out to improve care and wellbeing for frail elderly persons. The programme will come to an end in 2017. The results and lessons learned are being spread via the knowledge platform 'BeterOud'. In this article we describe some lessons from the programme for clinicians. The programme shows the value and the difficulties of clinicians taking the needs and wishes of frail elderly persons as the guiding principle of their care. Most frail elderly persons cannot be treated through generic interventions but need multidisciplinary and personalised care and support. In addition, standard research methods and outcome measures often do not coincide with the perceptions of elderly persons. This might explain the limited results of many projects in terms of cost-effectiveness. Benefits from the perspective of both professionals and elderly persons should be established in advance. PMID- 26906884 TI - [Acute appendicitis: preference for second ultrasound instead of CT or MRI]. AB - OBJECTIVE: To assess whether additional CT or MRI, rather than a repeat ultrasound investigation, is the most appropriate diagnostic approach for patients with clinical suspicion of appendicitis following an inconclusive first ultrasound. DESIGN: Descriptive study. METHOD: Retrospective data analysis of patients admitted to ER with clinical suspicion of acute appendicitis, on whom at least one ultrasonography had been performed. RESULTS: A total of 328 patients were included of which 81 patients had an inconclusive first ultrasonography. Twenty-five patients underwent a second ultrasound test, and in 17 patients a correct diagnosis could be made. The positive and negative predictive value of a second ultrasonography, following an inconclusive first one was 97% and 99% respectively. CONCLUSION: Following an inconclusive first ultrasonography in patients suspected of having acute appendicitis, a second ultrasound after an observation period can be considered, rather than opting for additional CT or MRI imaging. PMID- 26906885 TI - [CT strategy for patients with suspected acute appendicitis; comparison of conditional and immediate CT]. AB - OBJECTIVE: To compare the diagnostic accuracy of conditional CT strategy, i.e. CT if ultrasound findings are negative or inconclusive, with immediate CT strategy for patients with suspected appendicitis. DESIGN: Subanalysis of a prospective multicenter diagnostic accuracy study. METHOD: Only data of patients with signs of appendicitis based on medical history, physical examination, and laboratory tests were analyzed. All patients underwent both ultrasound and CT. Images of each were read by different observers who were blinded to the results of the other imaging modality. The observer then selected the most likely diagnosis. These diagnoses were compared with the reference standard, i.e. final diagnoses as assigned by an expert panel based on all available data and at least 6 months of follow-up. RESULTS: A total of 422 patients with suspected appendicitis were included. In 251 patients the final diagnosis was acute appendicitis (59%). In 199 patients (47%), ultrasound findings were inconclusive or negative. Use of conditional CT strategy resulted in correctly identified number of correctly identified patients with appendicitis, i.e. 96% (95% CI 93-98), versus 95% identified by immediate CT (95% CI 91-97). However, conditional CT strategy resulted in more false positive diagnoses compared with immediate CT (39 versus 22), had an accompanying lower specificity of 77% (95% CI 70-83) versus 87% (95% CI 81-91), and a lower positive predictive value of 86% (95% CI 81-90) versus 92% (95% CI 87-95). CONCLUSION: Use of a conditional CT strategy results in exactly the same number of patients with correctly identified acute appendicitis while halving the number of CTs needed. However, conditional strategy results in more false positive diagnoses. PMID- 26906886 TI - [Imported Zika virus infection in the Netherlands]. AB - Since mid-2015, a rapidly expanding outbreak of Zika virus infection is spreading across Latin America and the Caribbean. Although Zika virus infection usually causes only mild disease, the World Health Organization has declared the epidemiological association with the occurrence of congenital microcephaly and neurological complications a 'Public Health Emergency of International Concern' and urged the international community to mount a coordinated international response aimed to protect people at risk, especially pregnant women. In December 2015, the first case of imported Zika virus infection in the Netherlands was diagnosed in a returned traveler from Surinam. To date, more than 20 cases have been reported in The Netherlands, all imported from Surinam. We describe the epidemiology, clinical aspects, diagnostic challenges and the existing evidence to date that link Zika virus infection to complications. PMID- 26906887 TI - [Preterm birth and low socioeconomic status: more psychosocial problems at age 5 6?]. AB - OBJECTIVE: Comparison of the association between socioeconomic status (SES) and psychosocial problems in preterm-born and term-born children. DESIGN: Cohort study (Amsterdam Born Children and their Development (ABCD) cohort). METHOD: For 217 preterm-born children (mean gestation 34 weeks), Strengths and Difficulties Questionnaire (SDQ) scores were compared with 4336 term-born children at age 5-6 years. Associations between SDQ scores and SES (maternal education and perceived income adequacy) were examined with multivariate linear regression analysis. RESULTS: Mothers of preterm-born children often had a lower level of education. The mean SDQ total score was significantly higher for preterm-born children (6.1; SD: 4.7) than for term-born children (5.2; SD: 4.1). No significant differences were found between preterm-born and term-born children in the SDQ scores reported by teachers. For preterm-born children, 16.1% of the mothers reported psychosocial problems compared with 10.1% for term-born children. Lower maternal education and lower income adequacy were significantly related to higher SDQ scores. Differences in SDQ score between preterm-born and term-born children were most pronounced in the group with highly educated mothers (Delta0.9; 95%-CI: 0.2 1.5) and high income (Delta0.9; 95%-CI: 0.3-1.6). CONCLUSION: There was no additional effect of preterm birth on psychosocial problems in children with a low level of maternal education or inadequate income. This study corroborates earlier evidence regarding the disadvantageous effects of low SES on psychosocial development. PMID- 26906888 TI - [Which imaging technique in acute appendicitis?]. AB - This is a commentary on two published articles in this issue of the Dutch Journal of Medicine (NTvG) about the diagnosis and work-up of patients with suspected acute appendicitis. Despite a well-established Dutch guideline since 2010 in some cases the diagnosis of acute appendicitis remains a challenge. PMID- 26906889 TI - [Health inequalities: congenital or preventable?]. AB - Social deprivation is an important determinant of adverse obstetric and child developmental outcomes. A range of risk factors contribute to this link, many of which are potentially modifiable. Early screening for the many non-medical risk factors by healthcare workers should ideally commence in the preconceptual stage to maximise the potential health gain of any interventions. This is a shared responsibility of midwives, obstetricians, maternity nurses, paediatricians, and youth healthcare workers, who should actively collaborate in screening for medical and non-medical risks and in the subsequent institution of tailor-made care pathways. Researchers, healthcare workers, and policy makers should furthermore interact to achieve societal valorisation of knowledge, and thus reduce early-life social and health inequalities. PMID- 26906890 TI - Outcomes of post-cardiac surgery patients with persistent hyperlactatemia in the intensive care unit: a matched cohort study. AB - BACKGROUND: Higher morbidity and mortality rates are seen amongst patients presenting with hyperlactatemia in the postoperative period. The purpose of this study was to determine the relationship between persistent elevations in lactate and poor ICU outcome in post-cardiac surgery patients. METHODS: This was a retrospective matched cohort analysis of cardiac surgery patients undergoing bypass and/or valve surgery in a university hospital centre. Selection criteria were: cardiac bypass and/or valve surgery; admission to the ICU for > 24 h postoperatively; and peak lactate >= 3.0 mmol/L. Hyperlactatemic patients were matched to 2 normolactatemic patients. Multivariable conditional logistic regression was used to determine predictors of hyperlactatemia and mortality. RESULTS: Four hundred sixty-nine post-cardiac surgery patients were admitted to the ICU for > 24 h. 144 of these patients had an arterial blood lactate >= 3.0 mmol/L. Amongst the mortalities, 78.9 % presented with hyperlactatemia. Independent risk factors predictive of a lactate >= 3.0 mmol/L were preoperative IABP insertion (RR 2.8, CI 1.1-7.2) and postoperative acute kidney injury (RR 3.2, CI 2.1-5.4). Patients whose lactate concentrations continued to increase >30 h postoperatively were more likely to die (RR 8.44 CI 2.50-28.53). CONCLUSIONS: The persistence of hyperlactatemia is a more important determinant of postoperative outcome than the absolute value of the peak lactate concentration. A simple postoperative lactate washout does not sufficiently explain this lactate accumulation. Mortality is proposed to be secondary to a state of ongoing hypoperfusion. PMID- 26906891 TI - Global Atmospheric Transport and Source-Receptor Relationships for Arsenic. AB - Arsenic and many of its compounds are toxic pollutants in the global environment. They can be transported long distances in the atmosphere before depositing to the surface, but the global source-receptor relationships between various regions have not yet been assessed. We develop the first global model for atmospheric arsenic to better understand and quantify its intercontinental transport. Our model reproduces the observed arsenic concentrations in surface air over various sites around the world. Arsenic emissions from Asia and South America are found to be the dominant sources for atmospheric arsenic in the Northern and Southern Hemispheres, respectively. Asian emissions are found to contribute 39% and 38% of the total arsenic deposition over the Arctic and Northern America, respectively. Another 14% of the arsenic deposition to the Arctic region is attributed to European emissions. Our results indicate that the reduction of anthropogenic arsenic emissions in Asia and South America can significantly reduce arsenic pollution not only locally but also globally. PMID- 26906892 TI - First-principles calculation of the effects of Li-doping on the structure and piezoelectricity of (K0.5Na0.5)NbO3 lead-free ceramics. AB - The crystal structures of the lead-free piezoelectric ceramics (K0.5Na0.5)NbO3 and (K0.5Na0.5)0.94Li0.06NbO3 prepared by a solid-state method were investigated using first-principles calculations. The calculated values of piezoelectricity were in good agreement with the experimental data. We found that the primary contribution to piezoelectricity in this material comes from the hybridization of the O 2p and Nb 4d orbitals, which causes a change in the Nb-O bond length and the distortion of the Nb-O octahedral structure. Analysis of the band structure and the total density of states revealed that Li-doped (K0.5Na0.5)NbO3 enhances hybridization of the O 2p and Nb 4d orbitals. This hybridization enhancement further reduces the Nb-O1 bond length and enhances the distortion of the Nb-O octahedron along the [001] direction, which may be the main reason for the improvement of the piezoelectric properties. In addition, the piezoelectric coefficients are calculated here, which show the same trend as the experimental results. PMID- 26906893 TI - Spine Surgery in Patients with Metastatic Breast Cancer: A Retrospective Analysis. AB - BACKGROUND: Pathologic or iatrogenic symptomatic spinal lesions are common in metastatic breast cancer. Given the longer duration of overall survival provided by modern oncologic therapies, a prompt and effective treatment of such lesions may have a significant impact on patient's quality of life, improving pain and preventing deterioration of neurologic functions. METHODS: A retrospective review was conducted on patients with breast cancer operated to the spine between 2005 and 2013. The series includes 41 patients and 57 vertebral levels treated (4 cervical, 35 dorsal, and 18 lumbar). There were 28 patients who received palliative surgery and 13 who received excisional surgery, according to their clinical conditions, Spinal Instability Neoplastic Score, and Tokuhashi scores. RESULTS: Of the 41 patients, 38 presented with a median survival of 50 months (95% confidence interval [CI], 39-61), still preserving a Karnofsky Performance Status Scale score >=60 and a retained ability to ambulate independently. The median overall survival after the first spine surgery was also 50 months (95% CI, 35-65), suggesting that in this cohort of patients, a reasonable quality of life was preserved almost to the end of their clinical history. In patients treated with palliative surgery, the median survival was 37 months (95% CI, 26-48). In those treated with complex surgery, it was 57 months (95% CI, 41-73; P = 0.03). CONCLUSIONS: Major excisional surgery, albeit associated with an increased length of hospital stay, allowed in our series a prolonged survival compared with less aggressive types of surgery. However, percutaneous or open balloon kyphoplasty techniques have expanded indications for palliative surgery and even patients with lower Tokuhashi scores may benefit from rapid and sustained pain relief, preservation of neurologic function, and early mobilization. PMID- 26906894 TI - Anatomic Variations of the Floor of the Third Ventricle: An Endoscopic Study. AB - OBJECTIVE: Anatomical variations of the floor of the third ventricle are common in hydrocephalic patients and can significantly affect outcomes of endoscopic third ventriculostomy (ETV). We sought to categorize variations in third ventricle anatomy and to discuss the implications of these variations for ETV. METHODS: Intraoperative videos and pictures of 50 patients who underwent ETV between April 2001 and August 2010 were reviewed. Twenty-seven patients with clearly demonstrable third ventricular floors that satisfied our criteria were selected for the study. RESULTS: Images of variations were organized into the following categories: 1) thinned floor, 2) thickened floor, 3) partially effaced floor, 4) ballooning/herniating floor, 5) small prepontine interval, 6) narrowed third ventricle, and 7) other significant anomalies. CONCLUSIONS: The third ventricle is a common site for anatomical variations in hydrocephalic patients. A good knowledge of these variations is essential before performing ETV, because they have the potential to increase operative risk. PMID- 26906895 TI - Transient Delayed Hyponatremia After Transsphenoidal Surgery: Attempting to Enlighten the Epidemiology and Management of a Still-Obscure Complication. PMID- 26906896 TI - Cerebrovascular Events During Pregnancy and Puerperium Resulting from Preexisting Moyamoya Disease: Determining the Risk of Ischemic Events Based on Hemodynamic Status Assessment Using Brain Perfusion Single-Photon Emission Computed Tomography. AB - OBJECTIVE: The purposes of this study were to review the cerebrovascular events (CVE) during pregnancy and puerperium in adults with moyamoya disease (MMD) and to evaluate its risk factors. METHODS: We reviewed electronic medical records on 141 pregnancies in 71 women diagnosed with MMD and this study included only 27 pregnancies (23 patients) diagnosed with MMD before pregnancy. Basal and acetazolamide-stress brain perfusion single-photon emission computed tomography (SPECT) was conducted for 40 hemispheres in 21 pregnancies within 1 year of the gestational period, ranging from 22 months before delivery to 12 months after delivery for evaluation of the hemodynamic status of the patients to devise the MMD treatment strategy. RESULTS: Twelve pregnancies (44.4%) showed CVE during pregnancy or puerperium in the group diagnosed with MMD before pregnancy. All the 12 CVE were ischemic, without any hemorrhagic events. A decreased cerebral vascular reserve capacity (CVRC) on stress SPECT was observed in 25 (62.5%) of the 40 hemispheres, and 18 of these 25 hemispheres showed TIA. In contrast, only 2 of 15 hemispheres which revealed normal CVRC on stress SPECT showed TIA. Overall, a decreased CVRC on stress SPECT imaging was statistically associated with development of CVE (P < 0.001). Furthermore, the clinical type of MMD was also regarded as predictive factor for CVE in this study. Especially, ischemic type MMD revealed a statistical association with the development of CVE (P = 0.014, odds ratio = 16.50). CONCLUSIONS: Assessment of cerebral hemodynamic status with stress SPECT may predict CVE during pregnancy and puerperium. PMID- 26906897 TI - Helmet Use and Head Injury in Homer's Iliad. AB - BACKGROUND: Homer's detailed descriptions of head injuries inflicted during the Trojan War are of particular interest to individuals in the medical community. Although studies have examined the prevalence of such injuries, none have examined the preventive measures taken to avoid them. An in-depth review of helmet use in Homer's Iliad was conducted to address this previously unexplored facet of the epic. METHODS: An English translation of Homer's text was reviewed for all references to helmet use. The number of helmet references in each book was recorded, along with other pertinent details for each reference. RESULTS: There were 87 references to helmets (40 combat, 47 noncombat). The helmet belonged to a Greek warrior in 41 cases (47.1%), a Trojan warrior in 38 cases (43.6%), a divinity in 5 cases (5.7%), and a general group of warriors in 3 cases (3.4%). Helmet use provided protective benefit to Greek warriors at a rate of 30.0% (3 of 10) and Trojan warriors at a rate of 11.1% (2 of 18). This difference was not statistically significant (P = 0.23). The overall combined protective benefit of helmet use in the text was 17.9% (5 of 28). Helmets belonging to 15 specific Greek warriors and 18 specific Trojan warriors were referenced in the text. Helmets belonging to Hector (n = 12) and Achilles (n = 8) were most frequently mentioned. CONCLUSIONS: Helmet use and head injury both play a prominent role in Homer's Iliad. Helmets are frequently used in combat settings but with relatively little success. Helmets are also used in various noncombat settings. PMID- 26906898 TI - Ruptured True Anterior Choroidal Artery Aneurysm in Cisternal Segment. AB - BACKGROUND: Rupture of a true anterior choroidal artery (AChA) aneurysm in the cisternal segment is extremely rare, whereas cases of a distal AChA aneurysm associated with moyamoya disease are increasingly reported. CASE DESCRIPTION: A 58-year-old woman presented with a severe headache and vomiting. Computed tomography demonstrated a subarachnoid hemorrhage without intraventricular or intracerebral hemorrhaging. Cerebral angiogram findings revealed a proximal AChA aneurysm mimicking an internal carotid artery aneurysm at the origin of the AChA. Intraoperative findings demonstrated a ruptured aneurysm located on a bend of the proximal AChA in the carotid cistern. Neck clipping of the aneurysm with preservation of the AChA led to a good outcome. CONCLUSIONS: A rare case of ruptured true AChA aneurysm in the cisternal segment, unrelated to moyamoya disease, is presented as a cause of subarachnoid hemorrhage. PMID- 26906899 TI - Antidiabetic potential of two medicinal plants used in Gabonese folk medicine. AB - BACKGROUND: Diabetes mellitus is a metabolic disorder which is rising globally in rich and developing countries. In the African region this rate is the highest, with 20 million diagnosed diabetics. Despite a noticeable progress in the treatment of diabetes mellitus by synthetic drugs, the search for new natural anti-diabetic agents is going on. Nauclea diderrichii (De Wild.) Merr. (ND) and Sarcocephalus pobeguinii Hua ex Pellegr. (SP) are used as traditional medicines in Gabon for the treatment of different diseases, especially in the case of diabetes. The aim of this study was to evaluate the antidiabetic potential of these two medicinal plants traditionally used in Gabon. METHODS: Pharmacological (inhibitory action on alpha and beta-glucosidases) and toxicological (effect on human T cell proliferation) studies were conducted on aqueous extracts of ND (leaves and bark) and SP (bark) collected in Gabon. All raw extracts were analyzed by HPTLC and their content in phenolic compounds was determined by using standard method. The most active extracts were submitted to preparative HPLC in order to evidence the most efficient subfractions by biological evaluation. RESULTS: The results showed that two extracts from ND were potent alpha glucosidase inhibitors, the leaf extract being more active that the bark extract: the first one was more than 60 fold more active than Acarbose, which is an oral medication used to treat type 2 diabetes; the extract from SP bark was less efficient. The HPLC subfractions of the extracts of ND leaves and SP bark were tested in the same experimental conditions. In each case, the most active subfractions still show very potent inhibitory effect on alpha-glucosidase (80 90% inhibition at 0.1 mg/mL). The most efficient extract, from ND leaves, was also characterized by the highest percentage of phenolic compounds, which suggests a relationship between its inhibitory potential on alpha-glucosidase and its content in phenolic compounds. Conversely, only a moderate inhibitory activity of the three extracts was observed on beta-glucosidase. CONCLUSION: These results clearly indicated that active compounds present in N. diderrichii and S. pobeguinii leaves or/and bark were selective and highly potent inhibitors of alpha-glucosidase and validate their popular use for the treatment of diabetes. PMID- 26906900 TI - Difference in 24-Hour Urine Composition between Diabetic and Non-Diabetic Adults without Nephrolithiasis. AB - BACKGROUND: Diabetic patients are more likely to develop kidney stones than the general population. The underlying mechanisms for this disparity remain to be elucidated. Little is known about the relationship between urine composition and diabetes mellitus in non-stone-forming individuals. We sought to examine the differences in the 24-hour (24-h) urine composition between diabetic and non diabetic adults who were not stone formers. METHODS: A convenience sample of 538 individuals without a history of nephrolithiasis, gout, hyperparathyroidism, or gastroenteric diseases participated in this study. The 24-h urine profiles of 115 diabetic adults were compared with those of 423 non-diabetic adults. Diabetes was defined by self-reported physician diagnosis or medication use. All participants were non-stone formers confirmed by urinary tract ultrasonography. Participants provided a fasting blood sample and a single 24-h urine collection for stone risk analysis. Student's t-test was used to compare mean urinary values. Linear regression models were adjusted for age, gender, body mass index, hypertension, fasting serum glucose, serum total cholesterol, estimated creatinine clearance rate and urinary factors. RESULTS: Univariable analysis showed that the diabetic participants had significantly higher 24-h urine volumes and lower urine calcium and magnesium excretions than non-diabetic participants (all P < 0.05). After multivariate adjustment, no significant differences in 24-h urine composition were observed between diabetic and non-diabetic participants except for a slightly increased 24-h urine volume in diabetic participants (all P > 0.05). The main limitation of this study is that the convenience samples and self-reported data may have been sources of bias. CONCLUSION: Our data showed that there were no differences in 24-h urine composition between diabetic and non-diabetic adults who are not stone formers. The reason for it might be the improved glycemic control in diabetic individuals in our study. Therefore, a tighter glycemic control might reduce stone formation in diabetic adults. PMID- 26906902 TI - [There are differences in body weight between diets]. PMID- 26906901 TI - Platinum (IV)-fatty acid conjugates overcome inherently and acquired Cisplatin resistant cancer cell lines: an in-vitro study. AB - BACKGROUND: Platinum-based drugs are used as cancer chemotherapeutics for the last 40 years. However, drug resistance and nephrotoxicity are the major limitations of the use of platinum-based compounds in cancer therapy. Platinum (IV) complexes are believed to act as platinum prodrugs and are able to overcome some of platinum (II) limitations. METHODS: A number of previously sensitized platinum (IV) complexes were evaluated for their anti-cancer activity by monitoring ability to affect proliferation, clonigenicity and apoptosis induction of Cisplatin sensitive and resistant cancer cells. In addition, the uptake of Cisplatin and the platinum (IV) derivatives to Cisplatin sensitive and resistant cancer cells was monitored. RESULTS: The bis-octanoatoplatinum (IV) complex (RJY13), a Cisplatin derivative with octanoate as axial ligand, exhibited strong anti-proliferative effect on the Cisplatin resistant and sensitive ovarian cells, A2780cisR and A2780, respectively. Moreover, RJY13 exhibited good activity in inhibiting clonigenicity of both cells. Anti-proliferative activity of RJY13 was mediated by induction of apoptosis. Interestingly, a bis-lauratopaltinum (IV) complex (RJY6) was highly potent in inhibiting clonigenicity of both Cisplatin sensitive and Cisplatin resistant cells, however, exhibited reduced activity in assays that utilize cells growing in two dimensional (2D) conditions. The uptake of Cisplatin was reduced by 30% in A2780 in which the copper transporter-1 (Ctr1) was silenced. Moreover, uptake of RJY6 was marginally dependent on Ctr1, while uptake of RJY13 was Ctr1-independent. CONCLUSIONS: Our data demonstrated the potential of platinum (IV) prodrugs in overcoming acquired and inherited drug resistance in cancer cell lines. Moreover, our data demonstrated that the uptake of Cisplatin is partially dependent on Ctr1 transporter, while uptake of RJY6 is marginally dependent on Ctr1 and RJY13 is Ctr1-independent. In addition, our data illustrated the therapeutic potential of platinum (IV) prodrugs in cancer therapy. PMID- 26906903 TI - [Mullerianosis of the urinary bladder]. PMID- 26906904 TI - Polyethersulfone improves isothermal nucleic acid amplification compared to current paper-based diagnostics. AB - Devices based on rapid, paper-based, isothermal nucleic acid amplification techniques have recently emerged with the potential to fill a growing need for highly sensitive point-of-care diagnostics throughout the world. As this field develops, such devices will require optimized materials that promote amplification and sample preparation. Herein, we systematically investigated isothermal nucleic acid amplification in materials currently used in rapid diagnostics (cellulose paper, glass fiber, and nitrocellulose) and two additional porous membranes with upstream sample preparation capabilities (polyethersulfone and polycarbonate). We compared amplification efficiency from four separate DNA and RNA targets (Bordetella pertussis, Chlamydia trachomatis, Neisseria gonorrhoeae, and Influenza A H1N1) within these materials using two different isothermal amplification schemes, helicase dependent amplification (tHDA) and loop-mediated isothermal amplification (LAMP), and traditional PCR. We found that the current paper-based diagnostic membranes inhibited nucleic acid amplification when compared to membrane-free controls; however, polyethersulfone allowed for efficient amplification in both LAMP and tHDA reactions. Further, observing the performance of traditional PCR amplification within these membranes was not predicative of their effects on in situ LAMP and tHDA. Polyethersulfone is a new material for paper-based nucleic acid amplification, yet provides an optimal support for rapid molecular diagnostics for point-of-care applications. PMID- 26906905 TI - Intact Acquisition and Short-Term Retention of Non-Motor Procedural Learning in Parkinson's Disease. AB - Procedural learning is a form of memory where people implicitly acquire a skill through repeated practice. People with Parkinson's disease (PD) have been found to acquire motor adaptation, a form of motor procedural learning, similarly to healthy older adults but they have deficits in long-term retention. A similar pattern of normal learning on initial exposure with a deficit in retention seen on subsequent days has also been seen in mirror-reading, a form of non-motor procedural learning. It is a well-studied fact that disrupting sleep will impair the consolidation of procedural memories. Given the prevalence of sleep disturbances in PD, the lack of retention on following days seen in these studies could simply be a side effect of this well-known symptom of PD. Because of this, we wondered whether people with PD would present with deficits in the short-term retention of a non-motor procedural learning task, when the test of retention was done the same day as the initial exposure. The aim of the present study was then to investigate acquisition and retention in the immediate short term of cognitive procedural learning using the mirror-reading task in people with PD. This task involved two conditions: one where triads of mirror-inverted words were always new that allowed assessing the learning of mirror-reading skill and another one where some of the triads were presented repeatedly during the experiment that allowed assessing the word-specific learning. People with PD both ON and OFF their normal medication were compared to healthy older adults and young adults. Participants were re-tested 50 minutes break after initial exposure to probe for short-term retention. The results of this study show that all groups of participants acquired and retained the two skills (mirror-reading and word specific) similarly. These results suggest that neither healthy ageing nor the degeneration within the basal ganglia that occurs in PD does affect the mechanisms that underpin the acquisition of these new non-motor procedural learning skills and their short-term memories. PMID- 26906906 TI - Friedreich ataxia is not only a GAA repeats expansion disorder: implications for molecular testing and counselling. AB - Friedreich ataxia (FRDA) is the most common hereditary ataxia. It is an autosomal recessive disorder caused by mutations of the FXN gene, mainly the biallelic expansion of the (GAA)n repeats in its first intron. Heterozygous expansion/point mutations or deletions are rare; no patients with two point mutations or a point mutation/deletion have been described, suggesting that loss of the FXN gene product, frataxin, is lethal. This is why routine FRDA molecular diagnostics is focused on (GAA)n expansion analysis. Additional tests are considered only in cases of heterozygous expansion carriers and an atypical clinical picture. Analyses of the parent's carrier status, together with diagnostic tests, are performed in rare cases, and, because of that, we may underestimate the frequency of deletions. Even though FXN deletions are characterised as 'exquisitely rare,' we were able to identify one case (2.4 %) of a (GAA)n expansion/exonic deletion in a group of 41 probands. This was a patient with very early onset of disease with rapid progression of gait instability and hypertrophic cardiomyopathy. We compared the patient's clinical data to expansion/deletion carriers available in the literature and suggest that, in clinical practice, the FXN deletion test should be taken into account in patients with early-onset, rapid progressive ataxia and severe scoliosis. PMID- 26906907 TI - Fraudsters operate and officialdom turns a blind eye: a proposal for controlling stem cell therapy in China. AB - Stem cell tourism-the flow of patients from home countries to destination countries to obtain stem cell treatment-is a growing business in China. Many concerns have been raised regarding fraudsters that operate unsafe stem cell therapies and an officialdom that turns a blind eye to the questionable technology. The Chinese regulatory approach to stem cell research is based on Guidelines and Administrative Measures, rather than legislation, and may have no binding force on certain institutions, such as military hospitals. There is no liability and traceability system and no visible set of penalties for non compliance in the stem cell legal framework. In addition to the lack of safety and efficacy systems in the regulations, no specific expert authority has been established to monitor stem cell therapy to date. Recognizing the global nature of stem cell tourism, this article argues that resolving stem cell tourism issues may require not only the Chinese government but also an international mechanism for transparency and ethical oversight. A stringent set of international regulations that govern stem cell therapies can encourage China to improve stem cell regulation and enforcement to fulfill its obligations. Through an international consensus, a minimum standard for clinical stem cell research and a central enforcement system will be provided. As a result, rogue clinics that conduct unauthorized stem cell therapies can be penalized, and countries that are reluctant to implement the reconciled regulations should be sanctioned. PMID- 26906908 TI - Relative In Vitro Potentials of Parthenolide to Induce Apoptosis and Cell Cycle Arrest in Skin Cancer Cells. AB - BACKGROUND: Parthenolide (PN) has been reported to inhibit proliferation and induces apoptosis in a variety of cancer cells with different mechanisms. Nevertheless, to the best of our knowledge, its relative anticancer activity at lower doses has not been reported in HaCaT immortalized keratinocytes and A375 melanoma cells. OBJECTIVE AND METHOD: The present study aimed to investigate the relative anticancer effects of PN by analysing its cytotoxicity, apoptosis and cell cycle arresting potentials in HaCaT and A375 cells. RESULT: PN was found to be significantly cytotoxic with lower IC50 values of 1.45 uM and 2.9 uM (p<0.05) in HaCaT and A375 cells, respectively with nuclear disruption as evident by DAPI staining. A dose-dependent increase in DNA fragmentation indicated apoptotic cell death. Furthermore, the percentage of cells deposition at S (35.56 to 43.68%) and G0-G1 (27.15 to 56.44%) phases after 24 h of PN treatment, substantiate its cell cycle arresting potentials in HaCaT and A375 cells. CONCLUSION: These comparative results provided substantial evidence to conclude the anticancer potential of PN, especially at lower dosages to induce cell death mechanisms in skin epidermal cells. PMID- 26906909 TI - Anti-aging property of G2013 molecule as a novel immunosuppressive agent on enzymatic and non-enzymatic oxidative stress determinants in Rat model. AB - BACKGROUND: G2013 molecule is a novel non-steroidal anti-inflammatory agent with immunosuppressive property, which was investigated on determinants relative to the oxidative stress in animal model. MATERIALS AND METHODS: The Sprague-Dawley rats were used for evaluating properties of G2013 on some oxidative stress enzymes including: Myeloperoxidase (MPO), Glutathione peroxidase (GPX1), mitochondrial Superoxide dismutase (SOD2), Catalase (CAT), Glutathione S Transferase (GST), and inducible nitric oxide synthase (iNOS) genes expression by Real Time PCR. The rats were sacrificed 3 months after daily oral administration of G2013. Moreover, Malondialdehyde (MDA), Carbonyl protein (PCO), the lipid and protein oxidation markers respectively and total anti-oxidant capacity (TAC) were tested in serum by biochemical analysis. Also cortisol as a steroid hormone was evaluated by chemiluminescence immunoassay after 12 weeks consumption of G2013 solution. RESULT: Our findings revealed a significant decrease in MPO in G2013 treated group, indicating its favorable effects but has no significant effects on genes expression of another antioxidant enzymes, including: SOD2, CAT, GPX1, and GST. Also, there were no significant differences in PCO, TAC and cortisol compared to control group following G2013 consumption. While an enhancement in serum MDA level was observed in the treatment group. In addition, G2013 therapy did not show any weight loss. CONCLUSIONS: Our data showed the safety and efficacy of G2013 as a novel designed NSAID on various oxidative stress determinants. PMID- 26906910 TI - Pregnancy: Impact of Maternal Nutrition on Intrauterine Fetal Growth. PMID- 26906911 TI - Junior doctors announce three more 48 hour strikes. PMID- 26906912 TI - Thonzonium bromide inhibits RANKL-induced osteoclast formation and bone resorption in vitro and prevents LPS-induced bone loss in vivo. AB - Osteoclasts (OCs) play a pivotal role in a variety of lytic bone diseases including osteoporosis, arthritis, bone tumors, Paget's disease and the aseptic loosening of orthopedic implants. The primary focus for the development of bone protective therapies in these diseases has centered on the suppression of OC formation and function. In this study we report that thonzonium bromide (TB), a monocationic surface-active agent, inhibited RANKL-induced OC formation, the appearance of OC-specific marker genes and bone-resorbing activity in vitro. Mechanistically, TB blocked the RANKL-induced activation of NF-kappaB, ERK and c Fos as well as the induction of NFATc1 which is essential for OC formation. TB disrupted F-actin ring formation resulting in disturbances in cytoskeletal structure in mature OCs during bone resorption. Furthermore, TB exhibited protective effects in an in vivo murine model of LPS-induced calvarial osteolysis. Collectively, these data suggest that TB might be a useful alternative therapy in preventing or treating osteolytic diseases. PMID- 26906913 TI - Short-range growth inhibitory signals from the epithelium can drive non stereotypic branching in the pancreas. AB - Many organs such as the vasculature, kidney, lungs, pancreas and several other glands form ramified networks of tubes that either maximize exchange surfaces between two compartments or minimize the volume of an organ dedicated to the production and local delivery of a cell-derived product. The structure of these tubular networks can be stereotyped, as in the lungs, or stochastic with large variations between individuals, as in the pancreas. The principles driving stereotyped branching have attracted much attention and several models have been proposed and refined. Here we focus on the pancreas, as a model of non stereotyped branching. In many ramified tubular organs, an important role of the mesenchyme as a source of branching signals has been proposed, including in the pancreas. However, our previous work has shown that in the absence of mesenchyme, epithelial cells seeded in vitro in Matrigel form heavily branched organoids. Here we experimentally show that pancreatic organoids grow primarily at the tips. Furthermore, in contrast to classical 'depletion of activator' mechanisms, organoids growing in close vicinity seem not to affect each other's growth before they get in contact. We recapitulate these observations in an in silico model of branching assuming a 'local inhibitor' is secreted by the epithelium. Remarkably this simple mechanism is sufficient to generate branched organoids similar to those observed in vitro, including their transition from filled spheres to a tree like structure. Quantifying the similarity between in silico and in vitro development through a normalized surface to volume ratio, our in silico model predicts that inhibition is likely to be cooperative and that the diffusing inhibitor decays within a length scale of 10-20 MUm. PMID- 26906914 TI - Organoselenium and DMAP co-catalysis: regioselective synthesis of medium-sized halolactones and bromooxepanes from unactivated alkenes. AB - A catalytic system consisting of bis(4-methoxyphenyl)selenide and 4 (dimethylamino)pyridine (DMAP) has been developed for the regioselective synthesis of medium-sized bromo/iodo lactones and bromooxepanes possessing high transannular strain. (77)Se NMR, mass spectrometry and theoretical studies reveal that the reaction proceeds via a quaternary selenium intermediate. PMID- 26906915 TI - Prevalence of violence in childhood and adolescence and the impact on educational outcomes: evidence from the 2013 Peruvian national survey on social relations. PMID- 26906916 TI - Comments on the article "Antioxidants as a treatment for acute pancreatitis: A meta-analysis". PMID- 26906917 TI - Direct Mechanical Intervention Versus Combined Intravenous and Mechanical Intervention in Large Artery Anterior Circulation Stroke: A Matched-Pairs Analysis. AB - BACKGROUND AND PURPOSE: Five randomized controlled trials have consistently shown that mechanical thrombectomy (MT) in addition to best medical treatment (+/ intravenous tissue-type plasminogen activator) improves outcome after acute ischemic stroke in patients with large artery anterior circulation stroke. Whether direct MT is equally effective as combined intravenous thrombolysis with MT (ie, bridging thrombolysis) remains unclear. METHODS: We retrospectively compared clinical and radiological outcomes in 167 bridging patients with 255 patients receiving direct MT because of large artery anterior circulation stroke. We matched all patients from the direct MT group who would have qualified for intravenous tissue-type plasminogen activator with controls from the bridging group, using multivariate and propensity score analyses. Functional independence was defined as modified Rankin Scale score of 0 to 2. RESULTS: From February 2009 to August 2014, 40 patients from the direct MT group would have qualified for bridging thrombolysis but were treated with MT only. Clinical and radiological characteristics did not differ from the bridging cohort, except for higher rates of hypercholesterolemia (P=0.019), coronary heart disease (P=0.039), and shorter intervals from symptom onset to endovascular intervention (P=0.01) in the direct MT group. Functional independence, mortality, and intracerebral hemorrhage rates did not differ (P>0.1). After multivariate matching analysis outcome in both groups did not differ, except for lower rates of asymptomatic intracerebral hemorrhage (P=0.023) and lower mortality (P=0.007) in the direct MT group. CONCLUSIONS: In patients with large anterior circulation stroke, direct mechanical intervention seems to be equally effective as bridging thrombolysis. A randomized trial comparing direct MT with bridging therapy is warranted. PMID- 26906918 TI - Early Endovascular Treatment in Intravenous Tissue Plasminogen Activator Ineligible Patients. AB - BACKGROUND AND PURPOSE: Intravenous tissue-type plasminogen activator (tPA) treatment in acute stroke has many exclusion criteria. We aimed to assess the safety and efficacy of endovascular therapy (ET) in intravenous (IV) tPA ineligible patients. METHODS: Retrospective analysis of a prospectively collected database of consecutive patients treated with ET within 6 hours of stroke onset between September 2010 and April 2015. Patients treated with IV-tPA followed by ET were compared with those treated with ET alone because of IV-tPA ineligibility. Efficacy and safety end points included the rates of good outcome (90-day modified Rankin scale score <=2), successful reperfusion (modified Treatment in Cerebral Ischemia 2b-3), parenchymal hematoma (PH-1 and PH-2), and 90-day mortality. Univariate and logistic regression were performed to identify the predictors of outcomes. RESULTS: A total of 422 patients were included. Two hundred and fifty-three (59%) patients received IV-tPA+ET, and 169 (41%), ET alone. Combined IV-tPA+ET patients were slightly younger (64.9+/-15.2 versus 67.9+/-14.9 years; P=0.05), more often males (56% versus 44%; P=0.01), and had less hypertension (70% versus 81%; P=0.02) and vertebrobasilar occlusions (3% versus 8%; P=0.02). The remaining baseline characteristics, including National Institutes of Health Stroke Scale score (20 [15-23] versus 19 [15-24]; P=0.85), Alberta Stroke Program Early CT Score (ASPECTS; 8 [7-9] versus 8 [7-9]; P=0.24), and stroke onset to puncture times (235+/-70 versus 240+/-81 minutes; P=0.27), were similar across both groups. There were no significant differences in the rates of modified Treatment in Cerebral Ischemia 2b-3 (83% versus 80%; P=0.52), 90-day modified Rankin scale score <=2 (45% versus 38%; P=0.21), or any PH (3% versus 5%; P=0.21). Unadjusted 90-day mortality was higher with ET alone (21% versus 34%; P<0.01); however, IV-tPA ineligibility was not associated with modified Treatment in Cerebral Ischemia 2b-3, any PH, good outcome, or 90-day mortality on logistic regression. CONCLUSIONS: IV-tPA-eligible and -ineligible patients seem to have similar outcomes after early ET. PMID- 26906919 TI - International Stroke Genetics Consortium Update. PMID- 26906920 TI - Patient- and Aneurysm-Specific Risk Factors for Intracranial Aneurysm Growth: A Systematic Review and Meta-Analysis. AB - BACKGROUND AND PURPOSE: Follow-up imaging is often performed in intracranial aneurysms that are not treated. We performed a systematic review and meta analysis on patient- and aneurysm-specific risk factors for aneurysm growth. METHODS: We searched EMBASE and MEDLINE for cohort studies describing risk factors for aneurysm growth. Two authors independently assessed study eligibility and rated quality with the Newcastle Ottawa Scale. With univariable Poisson regression analysis, we calculated risk ratios (RRs) with corresponding 95% confidence intervals (95% CI) of risk factors for aneurysm growth. Heterogeneity was assessed with I(2). RESULTS: Eighteen studies on 15 patient-populations described 3990 patients with 4972 unruptured aneurysms. A total of 437 aneurysms (9%) enlarged during 13 987 aneurysm-years of follow-up. Compared with aneurysms <=4 mm, RRs were 2.56 (95% CI, 1.93-3.39; I(2)=98%) for >=5 mm, 2.80 (95% CI, 2.01-3.90; I(2)=96%) for >=7 mm, and 5.38 (95% CI, 3.76-7.70; I(2)=97%) for >=10 mm. Compared with aneurysms on the middle cerebral artery, the RR for basilar artery was 1.94 (95% CI, 1.32-2.83; I(2)=57%). RRs were 2.03 (95% CI, 1.52-2.71; I(2)=59%) for smoking at baseline, 2.04 (95% CI, 1.56-2.66; I(2)=90%) for multiple unruptured aneurysms, 1.26 (95% CI, 0.97-1.62; I(2)=59%) for women, 1.24 (95% CI, 0.98-1.58; I(2)=40%) for hypertension, and 2.32 (95% CI, 1.46-3.68; I(2)=91%) for irregular aneurysm shape. Compared with other regions, RR was 0.75 (95% CI, 0.58-0.96) for Japan and 0.64 (95% CI, 0.45-0.90) for Finland. CONCLUSIONS: Most risk factors for aneurysm growth are consistent with risk factors for rupture. In contrast with rupture, the risk of growth was smaller in Japanese and Finnish cohorts compared with other regions. Pooling of individual patient data from low- and high-risk geographical regions is needed to assess independent predictors of aneurysm growth. PMID- 26906921 TI - Corrigendum to: Ilk conditional deletion in adult animals increases cyclic GMP dependent vasorelaxation. AB - [Cardiovasc Res 2013; 99 (3):535-544] The authors wish to acknowledge the following funding information which was omitted from the above article: This work was supported by Health Institute Carlos III (PI1000612) cofunded with FEDER funds. The authors apologise for this omission. PMID- 26906923 TI - Nitrogen doped nanocrystalline semiconductor metal oxide: An efficient UV active photocatalyst for the oxidation of an organic dye using slurry Photoreactor. AB - Water pollution is a cause for serious concern in today's world. A major contributor to water pollution is industrial effluents containing dyes and other organic molecules. Waste water treatment has become a priority area in today's applied scientific research as it seeks to minimize the toxicity of the effluents being discharged and increase the possibility of water recycling. An efficient and eco-friendly way of degrading toxic molecules is to use nano metal-oxide photocatalysts. The present study aims at enhancing the photocatalytic activity of a semiconductor metal oxide by doping it with nitrogen. A sol-gel cum combustion method was employed to synthesize the catalyst. The prepared catalyst was characterized by FT-IR, XRD, UV-DRS, FESEM and AFM techniques. UV-DRS result showed the catalyst to possess band gap energy of 2.97eV, thus making it active in the UV region of the spectrum. Its photocatalytic activity was evaluated by the degradation of a model pollutant-Orange G dye, under UV light irradiation. Preliminary experiments were carried out to study the effects of pH, catalyst dosage and initial dye concentration on the extent of dye degradation. Kinetic studies revealed that the reaction followed pseudo first order kinetics. The effect of electrolytes on catalyst efficiency was also studied. The progress of the reaction was monitored by absorption studies and measuring the reduction in COD. The catalyst thus prepared was seen to have a high photocatalytic efficiency. The use of this catalyst is a promising means of waste water treatment. PMID- 26906922 TI - Francisella tularensis Modulates a Distinct Subset of Regulatory Factors and Sustains Mitochondrial Integrity to Impair Human Neutrophil Apoptosis. AB - Tularemia is a disease characterized by profound neutrophil accumulation and tissue destruction. The causative organism, Francisella tularensis, is a facultative intracellular bacterium that replicates in neutrophil cytosol, inhibits caspase activation and profoundly prolongs cell lifespan. Here, we identify unique features of this infection and provide fundamental insight into the mechanisms of apoptosis inhibition. Mitochondria are critical regulators of neutrophil apoptosis. We demonstrate that F. tularensis significantly inhibits Bax translocation and Bid processing during 24-48 h of infection, and in this manner sustains mitochondrial integrity. Downstream of mitochondria, X-linked inhibitor of apoptosis protein (XIAP) and proliferating cell nuclear antigen (PCNA) inhibit caspase-9 and caspase-3 by direct binding. Notably, we find that PCNA disappeared rapidly and selectively from infected cells, thereby demonstrating that it is not essential for neutrophil survival, whereas upregulation of calpastatin correlated with diminished calpain activity and reduced XIAP degradation. In addition, R-roscovitine is a cyclin-dependent kinase inhibitor developed for the treatment of cancer; it also induces neutrophil apoptosis and can promote the resolution of several infectious and inflammatory disorders. We confirm the ability of R-roscovitine to induce neutrophil apoptosis, but also demonstrate that its efficacy is significantly impaired by F. tularensis. Collectively, our findings advance the understanding of neutrophil apoptosis and its capacity to be manipulated by pathogenic bacteria. PMID- 26906924 TI - Chondroitin sulfate interacts mainly with headgroups in phospholipid monolayers. AB - Sulfated glycosaminoglycans are precursors of the extracellular matrix used to treat diseases related to blood clotting and degenerative joint diseases. These medical applications have been well established, but the mode of action at the molecular level, which depends on the interaction with cell membranes, is not known in detail. In this study, we investigated the interaction between chondroitin sulfate (CS) and phospholipid monolayers that mimic cell membranes. From surface pressure isotherms and polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS), CS was found to interact mainly with the polar groups of dipalmitoyl phosphatidylcholine (DPPC) and dipalmitoyl phosphatidylglycerol (DPPG), with negligible penetration into the hydrophobic tails and only small changes in monolayer elasticity for the packing corresponding to a real cell membrane. The changes in surface pressure and surface potential isotherms depended on CS concentration and on the time allowed for its adsorption onto the monolayer, which points to a dynamic adsorption desorption process. The charge of the phospholipid was also relevant, since CS induced order into DPPC monolayers while the opposite occurred for DPPG, according to the PM-IRRAS spectra. In summary, interaction with polar groups is responsible for the CS effects on model cell membranes. PMID- 26906925 TI - A novel proximal end stenting technique for assisting embolization of a complex true posterior communicating aneurysm. AB - Stent-assisted coiling has been widely used for endovascular treatment in recent years with satisfying clinical outcomes. The implantation of a stent using the regular approach, however, may not be safe or effective for certain aneurysms with complex structures. In this study, we report a novel stenting technique utilizing the proximal end of the stent for assisting embolization of a wide-neck irregular true posterior communicating aneurysm. This new method is a potential treatment strategy for wide-neck aneurysms located at the origin of a tortuous and thin vessel. PMID- 26906926 TI - Efficacy of sarolaner in the prevention of Borrelia burgdorferi and Anaplasma phagocytophilum transmission from infected Ixodes scapularis to dogs. AB - The efficacy of sarolaner (SimparicaTM, Zoetis) to prevent transmission primarily of Borrelia burgdorferi and secondarily of Anaplasma phagocytophilum from infected wild-caught Ixodes scapularis to dogs was evaluated in a placebo controlled laboratory study. Twenty-four purpose-bred laboratory Beagles seronegative for B. burgdorferi and A. phagocytophilum antibodies were allocated randomly to one of three treatment groups: placebo administered orally on Days 0 and 7, or sarolaner at 2mg/kg administered orally on Day 0 (28 days prior to tick infestation) or on Day 7 (21 days prior to tick infestation). On Day 28, each dog was infested with approximately 25 female and 25 male wild caught adult I. scapularis that were determined to have prevalence of 57% for B. burgdorferi and 6.7% for A. phagocytophilum by PCR. In situ tick counts were conducted on Days 29 and 30. On Day 33, all ticks were counted and removed. Acaricidal efficacy was calculated based on the reduction of geometric mean live tick counts in the sarolaner-treated groups compared to the placebo-treated group for each tick count. Blood samples collected from each dog on Days 27, 49, 63, 77, 91 and 104 were tested for the presence of B. burgdorferi and A. phagocytophilum antibodies using the SNAP((r)) 4Dx((r)) Plus Test, and quantitatively assayed for B. burgdorferi antibodies using an ELISA test. Skin biopsies collected on Day 104 were tested for the presence of B. burgdorferi by bacterial culture and PCR. Geometric mean live tick counts for placebo-treated dogs were 14.8, 12.8, and 19.1 on Days 29, 30, and 33, respectively. The percent reductions in mean live tick counts at 1, 2, and 5 days after infestation were 86.3%, 100%, and 100% for the group treated with sarolaner 21 days prior to infestation, and 90.9%, 97.1%, and 100% for the group treated with sarolaner 28 days prior to infestation. Geometric mean live tick counts for both sarolaner-treated groups were significantly lower than those for the placebo group on all count days (P<0.0001). There were no adverse reactions to treatment with sarolaner. Transmission of B. burgdorferi to all eight placebo-treated dogs was confirmed by positive antibody (6 of 8 dogs), PCR (7 of 8 dogs), and/or culture (7 of 8 dogs). Similarly, transmission of A. phagocytophilum was confirmed by the presence of antibodies in four placebo-treated dogs. In contrast, treatment with a single dose of sarolaner prevented transmission of B. burgdorferi from infected ticks to dogs infested 21 or 28 days after treatment as demonstrated by negative antibody, PCR, and culture results. Prevention of transmission of A. phagocytophilum was demonstrated by negative antibody results in all sarolaner-treated dogs. PMID- 26906927 TI - Team-Based Telecare for Bipolar Disorder. AB - INTRODUCTION: Numerous randomized controlled trials indicate that collaborative chronic care models improve outcome in a wide variety of mental health conditions, including bipolar disorder. However, their spread into clinical practice is limited by the need for a critical mass of patients and specialty providers in the same locale. Clinical videoconferencing has the potential to overcome these geographic limitations. MATERIALS AND METHODS: A videoconference based collaborative care program for bipolar disorder was implemented in the Department of Veterans Affairs. Program evaluation assessed experience with the first 400 participants, guided by five domains specified by the American Telemedicine Association: treatment engagement, including identification of subpopulations at risk for not being reached; participation in treatment; clinical impact; patient safety; and quality of care. RESULTS: Participation rates resembled those for facility-based collaborative care. No participant characteristics predicted nonengagement. Program completers demonstrated significant improvements in several clinical indices, without evidence of compromise in patient safety. Guideline-based quality of care assessment after 1 year indicated increased lithium use, decreased antidepressant use, and increased prazosin use in individuals with comorbid post-traumatic stress disorder, but no impact on already high rates of lithium serum level monitoring. DISCUSSION: Clinical videoconferencing can extend the reach of collaborative care models for bipolar disorder. The next step involves assessment of the videoconference-based collaborative care for other serious mental health conditions, investigation of barriers and facilitators of broad implementation of the model, and evaluation of the business case for deployment and sustainability in clinical practice. PMID- 26906928 TI - Crystal Structures of the uL3 Mutant Ribosome: Illustration of the Importance of Ribosomal Proteins for Translation Efficiency. AB - The ribosome has been described as a ribozyme in which ribosomal RNA is responsible for peptidyl-transferase reaction catalysis. The W255C mutation of the universally conserved ribosomal protein uL3 has diverse effects on ribosome function (e.g., increased affinities for transfer RNAs, decreased rates of peptidyl-transfer), and cells harboring this mutation are resistant to peptidyl transferase inhibitors (e.g., anisomycin). These observations beg the question of how a single amino acid mutation may have such wide ranging consequences. Here, we report the structure of the vacant yeast uL3 W255C mutant ribosome by X-ray crystallography, showing a disruption of the A-site side of the peptidyl transferase center (PTC). An additional X-ray crystallographic structure of the anisomycin-containing mutant ribosome shows that high concentrations of this inhibitor restore a "WT-like" configuration to this region of the PTC, providing insight into the resistance mechanism of the mutant. Globally, our data demonstrate that ribosomal protein uL3 is structurally essential to ensure an optimal and catalytically efficient organization of the PTC, highlighting the importance of proteins in the RNA-centered ribosome. PMID- 26906929 TI - Trigger Factor Reduces the Force Exerted on the Nascent Chain by a Cotranslationally Folding Protein. AB - Cotranslational protein folding can generate pulling forces on the nascent chain that can affect the instantaneous translation rate and thereby possibly feed back on the folding process. Such feedback would represent a new way of coupling translation and folding, different from coupling based on, for example, codon usage. However, to date, we have carried out the experiments used to measure pulling forces generated by cotranslational protein folding either in reconstituted in vitro translation systems lacking chaperones, in ill-defined cell lysates, or in vivo; hence, the effects of chaperones on force generation by folding are unknown. Here, we have studied the cotranslational folding of dihydrofolate reductase (DHFR) in the absence and in the presence of the chaperones trigger factor (TF) and GroEL/ES. DHFR was tethered to the ribosome via a C-terminal linker of varying length, ending with the SecM translational arrest peptide that serves as an intrinsic force sensor reporting on the force generated on the nascent chain when DHFR folds. We find that DHFR folds into its native structure only when it has emerged fully outside the ribosome and that TF and GroEL alone substantially reduces the force generated on the nascent chain by the folding of DHFR, while GroEL/ES has no effect. TF therefore weakens the possible coupling between cotranslational folding and translation. PMID- 26906930 TI - Chemokine gene variants in schizophrenia. AB - Background Chemokines are known to play a major role in driving inflammation and immune responses in several neuroinflammatory diseases, including multiple sclerosis, Alzheimer's disease and Parkinson's disease. Inflammation has also been implicated in the pathogenesis of schizophrenia. Aim We aimed to investigate a potential link between chemokines and schizophrenia and analyze the role of MCP 1-A2518G, SDF-1-3'A, CCR5-delta32, CCR5-A55029G, CXCR4-C138T and CCR2-V64I gene polymorphisms in the Turkish population. Methods Genotyping was conducted by PCR RFLP based on 140 patients and 123 unrelated healthy controls to show the relation between chemokine gene variants and schizophrenia risk. Results Frequencies of CCR5-A55029G A genotypes and CCR5-A55029G AG genotypes were found higher in patients than the controls and even also CCR2-V64I WT: CCR5-A55029G A and CCR2-V64I 64I: CCR5-A55029G A haplotypes significantly associated according to Bonferroni correction. However, no significant association was found for any of the other polymorphisms with the risk of schizophrenia. Conclusions Our findings suggest that CCR5-A55029G polymorphisms and CCR2-V64I WT: CCR5-A55029G A and CCR2-V64I 64I: CCR5-A55029G A haplotypes might have association with schizophrenia pathogenesis. PMID- 26906931 TI - Enzymatic transhalogenation of dendritic RGD peptide constructs with the fluorinase. AB - The substrate scope of fluorinase enzyme mediated transhalogenation reactions is extended. Substrate tolerance allows a peptide cargo to be tethered to a 5' chloro-5'-deoxynucleoside substrate for transhalogenation by the enzyme to a 5' fluoro-5'-deoxynucleoside. The reaction is successfully extended from that previously reported for a monomeric cyclic peptide (cRGD) to cargoes of dendritic scaffolds carrying two and four cyclic peptide motifs. The RGD peptide sequence is known to bind upregulated alphaVbeta3 integrin motifs on the surface of cancer cells and it is demonstrated that the fluorinated products have a higher affinity to alphaVbeta3 integrin than their monomeric counterparts. Extending the strategy to radiolabelling of the peptide cargoes by tagging the peptides with [(18)F]fluoride was only moderately successful due to the poor water solubility of these higher order peptide scaffolds although the strategy holds promise for peptide constructs with improved solubility. PMID- 26906932 TI - Genetically modified bacteriophages. AB - Phages or bacteriophages, viruses that infect and replicate inside bacteria, are the most abundant microorganisms on earth. The realization that antibiotic resistance poses a substantial risk to the world's health and global economy is revitalizing phage therapy as a potential solution. The increasing ease by which phage genomes can be modified, owing to the influx of new technologies, has led to an expansion of their natural capabilities, and a reduced dependence on phage isolation from environmental sources. This review will discuss the way synthetic biology has accelerated the construction of genetically modified phages and will describe the wide range of their applications. It will further provide insight into the societal and economic benefits that derive from the use of recombinant phages in various sectors, from health to biodetection, biocontrol and the food industry. PMID- 26906933 TI - Feather hydrolysate from Streptomyces sampsonii GS 1322: A potential low cost soil amendment. AB - Process parameters for obtaining hydrolysate from hen feathers, i.e., initial pH (5.0-9.0) and incubation period (1-6 day), were set and studied, using Streptomyces sampsonii GS 1322 in submerged and solid state conditions. Under submerged conditions, complete hydrolysis of feathers was observed on fifth day [initial pH 8.0, 28 +/- 2 degrees C, shaking (150 rpm)] with release of soluble protein (2985 MUg ml(-1)) and amino acids (2407 MUg ml(-1)). Cell free hydrolysate showed hydrolysis of casein (18 mm), gelatin (26 mm), collagen (31 mm), hemoglobin (23 mm) and Tween 80 (35 mm) while 445 U keratinase activity. Total soluble protein reached 5 mg ml(-1) in solid state conditions. During Pot experimentation using barren agriculture soil the effect of feather hydrolysate on wheat crop were recorded. Significant increase (p<0.01) in wheat seed germination was observed in treated soils as compared to untreated. Treatment significantly increased plant height from 30 to 60 days and 30-90 days (p<0.001). Treated soil showed an increase in total microbial count, proteolytic activity, phosphate solubilizing bacteria and ammonifying bacteria, whereas pathogenic fungi load was reduced. S. sampsonii GS 1322 can be used for bio-processing of poultry wastes yielding feather hydrolysate rich in proteins and amino acids for development of low-cost organic amendment to accelerate wheat crop growth in barren agricultural land. PMID- 26906934 TI - Modified harvest system for enhancing Factor VIII yield in alternating tangential flow perfusion culture. AB - This study describes the development and experimental verification of a modified harvest system to enhance Factor VIII (FVIII) yield in an alternating tangential flow (ATF) perfusion culture. The main innovation of the modified harvest system is the use of check and pinch valves, eliminating the need of a peristaltic pump for harvest. The system was applied to perfusion cultures of Chinese hamster ovary cells, which co-express both recombinant human FVIII (rhFVIII) and von Willebrand factor (vWF). The modified harvest system showed comparable cell growth with the conventional harvest system using a peristaltic pump. The perfusion rate was successfully controlled using the system. In addition, the modified harvest system achieved an approximately 13.6-fold increase in the final concentration yield of FVIII activity and a 1.47-fold increase in the production yield of FVIII activity compared with a peristaltic pump. Enhancement of the yield of FVIII activity resulted from the reduction of FVIII antigen ( FVIII: Ag) retention. As a result of transmembrane pressure (TMP) measurement, the reduction of the retained FVIII: Ag was due to the increased TMP, which was caused by the characteristic function of a check valve, compared with a peristaltic harvest system. The modified harvest system developed in this study could be useful to enhance the production yield of other recombinant proteins in ATF perfusion culture. PMID- 26906935 TI - A survey of patient expectations regarding sexual function following radical prostatectomy. AB - OBJECTIVE: To assess the understanding of patients, who had previously undergone radical prostatectomy (RP), about their postoperative sexual function, as clinical experience suggests that some RP patients have unrealistic expectations about their long-term sexual function. PATIENTS AND METHODS: Patients presenting within 3 months of their open RP or robot-assisted laparoscopic prostatectomy (RALP) were questioned about the sexual function information that they had received preoperatively. Patients were questioned about erectile function (EF), postoperative ejaculatory status, orgasm, and postoperative penile morphology changes. Statistical analyses were performed to assess for differences between patients who underwent open RP vs RALP. RESULTS: In all, 336 consecutive patients (from nine surgeons) with a mean (SD) age of 64 (11) years had the survey instrument administered (216 underwent open RP and 120 underwent RALP). There were no significant differences in patient age or comorbidity profiles between the two groups. Only 38% of men had an accurate recollection of their nerve sparing status. The mean (SD) elapsed time after RP at the time of postoperative assessment was 3 (2) months. RALP patients expected a shorter EF recovery time (6 vs 12 months, P = 0.02), a higher likelihood of recovery back to baseline EF (75% vs 50%, P = 0.01), and a lower potential need for intracavernosal injection therapy (4% vs 20%, P = 0.01). Almost half of all patients were unaware that they were rendered anejaculatory by their surgery. None of the RALP patients and only 10% of open RP patients recalled being informed of the potential for penile length loss (P < 0.01) and none were aware of the association between RP and Peyronie's disease. CONCLUSIONS: Patients who have undergone RP have largely unrealistic expectations about their postoperative sexual function. PMID- 26906936 TI - Exploiting Multiple Descriptor Sets in QSAR Studies. AB - A quantitative structure-activity relationship (QSAR) is a model relating a specific biological response to the chemical structures of compounds. There are many descriptor sets available to characterize chemical structure, raising the question of how to choose among them or how to use all of them for training a QSAR model. Making efficient use of all sets of descriptors is particularly problematic when active compounds are rare among the assay response data. We consider various strategies to make use of the richness of multiple descriptor sets when assay data are poor in active compounds. Comparisons are made using data from four bioassays, each with five sets of molecular descriptors. The recommended method takes all available descriptors from all sets and uses an algorithm to partition them into groups called phalanxes. Distinct statistical models are trained, each based on only the descriptors in one phalanx, and the models are then averaged in an ensemble of models. By giving the descriptors a chance to contribute in different models, the recommended method uses more of the descriptors in model averaging. This results in better ranking of active compounds to identify a shortlist of drug candidates for development. PMID- 26906937 TI - Modifying the Glycome in Pigs for Xenotransplantation. PMID- 26906938 TI - Immunogenicity of Renal Microvascular Endothelial Cells From Genetically Modified Pigs. AB - BACKGROUND: Disrupting the porcine GGTA1 and CMAH genes [double knockout (DKO)] that produce the gal-alpha(1,3)-gal and N-glycolylneuraminic acid xenoantigens reduces human antibody binding to porcine peripheral blood mononuclear cells. It is important to examine rejection pathways at an organ-specific level. The object of this study is to evaluate the human preformed antibody reactivity against DKO renal microvascular endothelial cells (RMEC) in vitro. METHODS: Characteristics of DKO RMEC were analyzed using flow cytometry. Human IgG/M binding to primary RMEC, immortalized RMEC (iRMEC), and iRMEC-deficient in B4GALNT2 genes were examined using flow cytometric crossmatch assay. RESULTS: Porcine RMEC expressed gal-alpha(1,3)-gal, N-glycolylneuraminic acid, and Dolichos biflorus agglutinin glycans recognized by human preexisting antibodies in humans. Antigenicity of DKO RMEC was lower than GGTA1 KO RMEC. The disruption of B4GALNT2 gene in DKO iRMEC further reduced human IgG/IgM binding. CONCLUSIONS: Silencing the porcine GGTA1, CMAH, and B4GALNT2 genes is an effective strategy to reduce human preformed antibody binding to RMEC. Porcine RMEC will be a useful reagent for the further study of xenoimmunology. PMID- 26906939 TI - Silencing Porcine CMAH and GGTA1 Genes Significantly Reduces Xenogeneic Consumption of Human Platelets by Porcine Livers. AB - BACKGROUND: A profound thrombocytopenia limits hepatic xenotransplantation in the pig-to-primate model. Porcine livers also have shown the ability to phagocytose human platelets in the absence of immune-mediated injury. Recently, inactivation of the porcine ASGR1 gene has been shown to decrease this phenomenon. Inactivating GGTA1 and CMAH genes has reduced the antibody-mediated barrier to xenotransplantation; herein, we describe the effect that these modifications have on xenogeneic consumption of human platelets in the absence of immune-mediated graft injury. METHODS: Wild type (WT), ASGR1, GGTA1, and GGTA1CMAH knockout pigs were compared for their xenogeneic hepatic consumption of human platelets. An in vitro assay was established to measure the association of human platelets with liver sinusoidal endothelial cells (LSECs) by immunohistochemistry. Perfusion models were used to measure human platelet uptake in livers from WT, ASGR1, GGTA1, and GGTA1 CMAH pigs. RESULTS: GGTA1, CMAH LSECs exhibited reduced levels of human platelet binding in vitro when compared with GGTA1 and WT LSECs. In a continuous perfusion model, GGTA1 CMAH livers consumed fewer human platelets than GGTA1 and WT livers. GGTA1 CMAH livers also consumed fewer human platelets than ASGR1 livers in a single-pass model. CONCLUSIONS: Silencing the porcine carbohydrate genes necessary to avoid antibody-mediated rejection in a pig-to human model also reduces the xenogeneic consumption of human platelets by the porcine liver. The combination of these genetic modifications may be an effective strategy to limit the thrombocytopenia associated with pig-to-human hepatic xenotransplantation. PMID- 26906940 TI - Elevated Urinary Matrix Metalloproteinase-7 Detects Underlying Renal Allograft Inflammation and Injury. AB - BACKGROUND: The urinary CXC chemokine ligand (CXCL)10 detects renal transplant inflammation noninvasively, but has limited sensitivity and specificity. In this study, we performed urinary proteomic analysis to identify novel biomarkers that may improve the diagnostic performance of urinary CXCL10 for detecting alloimmune inflammation in renal transplant patients. METHODS: In preliminary studies, adult renal transplant patients with normal histology (n = 5), interstitial fibrosis and tubular atrophy (n = 6), subclinical (n = 6) and clinical rejection (n = 6), underwent in-depth urine protein compositional analysis with LC-MS/MS, and matrix metalloproteinase-7 (MMP7) were identified as a potential candidate for the diagnosis of renal allograft inflammation. Urine MMP7 performance was then studied in a larger, prospective adult renal transplant population (n = 148 urines from n = 133 patients) with matched surveillance/indication biopsies. The diagnostic performance of urinary MMP7 and CXCL10 in combination was next evaluated using concordance (C-) statistics, net reclassification improvement and integrated discrimination improvement indices, to determine whether it was better than CXCL10 alone. RESULTS: Urinary MMP7:creatinine (Cr) was lower in normal transplants compared to those with inflammation: glomerulonephritis (P = 0.009), viral nephropathies (P = 0.002), interstitial fibrosis and tubular atrophy and inflammation (P = 0.04), borderline (P = 0.08), subclinical (P = 0.01) and clinical rejection (P = 0.0006), and acute tubular necrosis (P < 0.0001). Urinary MMP7:Cr and CXCL10:Cr significantly distinguished noninflamed from inflamed biopsies (area under the curve, 0.74 and 0.70, respectively). The addition of urinary MMP7:Cr to CXCL10:Cr improved the diagnostic performance for subclinical and clinical inflammation/injury by integrated discrimination improvement (P = 0.002) and net reclassification improvement (P = 0.006) analyses. CONCLUSIONS: Urinary MMP7:Cr improves the overall diagnostic performance of urinary CXCL10:Cr for distinguishing normal histology from subclinical and clinical inflammation/injury, but not subclinical inflammation alone. PMID- 26906941 TI - Outcomes Following Cubital Tunnel Surgery in Young Patients: The Importance of Nerve Mobility. AB - PURPOSE: To investigate the outcomes following surgical management of unstable and stable ulnar nerves at the elbow in young patients. METHODS: We retrospectively reviewed the charts of 67 patients who were 30 years old or younger when they underwent primary cubital tunnel surgery at our institution over a 10-year period. In 34 (45%) of these patients, the ulnar nerve either subluxated or perched on the medial epicondyle with elbow flexion and made up the "unstable" cohort. The remaining 42 patients made up the "stable" cohort. Preoperative, intraoperative, and postoperative data were obtained from the patients' charts. Thirty-nine patients completed the following outcome measures: Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH), visual analog scale (VAS) for pain and treatment satisfaction, return to sport or full activities, and the presence of persistent symptoms. RESULTS: At an average of 5.6 years following surgery, the unstable cohort had a significantly lower QuickDASH score (6.4 vs 18.6) and a significantly higher VAS for treatment satisfaction (8.7 vs 5.9) compared with the stable cohort. The unstable cohort was also significantly less likely to experience residual symptoms (43% vs 94%), persistent numbness (39% vs 44%), or persistent tingling (22% vs 56%) compared with the stable cohort. Within the stable cohort, patients who underwent simultaneous carpal tunnel release exhibited improved VAS and QuickDASH scores compared with patients who did not. There were no differences in time to return to sports or full activities or pain VAS between the two groups. CONCLUSIONS: Surgical management of young patients with symptomatic, unstable ulnar nerves results in superior subjective outcomes compared with surgery in young patients with stable ulnar nerves. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III. PMID- 26906943 TI - [Advantages of continuous subcutaneous insulin infusion vs. multiple daily injections for the treatment of subjects with type 1 diabetes: Are there still doubts?]. PMID- 26906942 TI - Development of immune-diagnostic reagents to diagnose bovine tuberculosis in cattle. AB - Bovine tuberculosis remains a major economic and animal welfare concern worldwide. As part of control strategies, cattle vaccination is being considered. This approach, used alongside conventional control policies, also requires the development of vaccine compatible diagnostic assays to distinguish infected from vaccinated animals (DIVA). In this review we discuss recent advances in DIVA development based on the detection of host cellular immune responses by blood testing or skin testing approaches. PMID- 26906944 TI - An appraisal of current dysphagia diagnosis and treatment strategies. AB - Dysphagia is a common, serious health problem with a wide variety of etiologies and manifestations. This review gives a general overview of diagnostic and therapeutic options for oropharyngeal as well as esophageal swallowing disorders respecting the considerable progress made over recent years. Diagnosis can be challenging and requires expertise in interpretation of symptoms and patient history. Endoscopy, barium radiography and manometry are still the diagnostic mainstays. Classification of esophageal motor-disorders has been revolutionized with the introduction of high-resolution esophageal pressure topography and a new standardized classification algorithm. Automated integrated impedance manometry is a promising upcoming tool for objective evaluation of oropharyngeal dysphagia, in non-obstructive esophageal dysphagia and prediction of post fundoplication dysphagia risk. Impedance planimetry provides new diagnostic information on esophageal and LES-distensibility and allows controlled therapeutic dilatation without the need for radiation. Peroral endoscopic myotomy is a promising therapeutic approach for achalasia and spastic motility disorders. PMID- 26906945 TI - A photon-working on/off switch for intramolecular donor-acceptor interactions and invisible modulation of the fluorescence. AB - An on/off switching for charge-transfer interactions between the side chains of a diarylethene based on photochromic reactions has been proved by the disappearance and appearance of an additional fluorescence band. PMID- 26906946 TI - Transcriptome sequencing of Crucihimalaya himalaica (Brassicaceae) reveals how Arabidopsis close relative adapt to the Qinghai-Tibet Plateau. AB - The extreme environment of the Qinghai-Tibet Plateau (QTP) provides an ideal natural laboratory for studies on adaptive evolution. Few genome/transcriptome based studies have been conducted on how plants adapt to the environments of QTP compared to numerous studies on vertebrates. Crucihimalaya himalaica is a close relative of Arabidopsis with typical QTP distribution, and is hoped to be a new model system to study speciation and ecological adaptation in extreme environment. In this study, we de novo generated a transcriptome sequence of C. himalaica, with a total of 49,438 unigenes. Compared to five relatives, 10,487 orthogroups were shared by all six species, and 4,286 orthogroups contain putative single copy gene. Further analysis identified 487 extremely significantly positively selected genes (PSGs) in C. himalaica transcriptome. Theses PSGs were enriched in functions related to specific adaptation traits, such as response to radiation, DNA repair, nitrogen metabolism, and stabilization of membrane. These functions are responsible for the adaptation of C. himalaica to the high radiation, soil depletion and low temperature environments on QTP. Our findings indicate that C. himalaica has evolved complex strategies for adapting to the extreme environments on QTP and provide novel insights into genetic mechanisms of highland adaptation in plants. PMID- 26906947 TI - Deuterated detergents for structural and functional studies of membrane proteins: Properties, chemical synthesis and applications. AB - Detergents are amphiphilic compounds that have crucial roles in the extraction, purification and stabilization of integral membrane proteins and in experimental studies of their structure and function. One technique that is highly dependent on detergents for solubilization of membrane proteins is solution-state NMR spectroscopy, where detergent micelles often serve as the best membrane mimetic for achieving particle sizes that tumble fast enough to produce high-resolution and high-sensitivity spectra, although not necessarily the best mimetic for a biomembrane. For achieving the best quality NMR spectra, detergents with partial or complete deuteration can be used, which eliminate interfering proton signals coming from the detergent itself and also eliminate potential proton relaxation pathways and strong dipole-dipole interactions that contribute line broadening effects. Deuterated detergents have also been used to solubilize membrane proteins for other experimental techniques including small angle neutron scattering and single-crystal neutron diffraction and for studying membrane proteins immobilized on gold electrodes. This is a review of the properties, chemical synthesis and applications of detergents that are currently commercially available and/or that have been synthesized with partial or complete deuteration. Specifically, the detergents are sodium dodecyl sulphate (SDS), lauryldimethylamine-oxide (LDAO), n-octyl-beta-D-glucoside (beta-OG), n-dodecyl beta-D-maltoside (DDM) and fos-cholines including dodecylphosphocholine (DPC). The review also considers effects of deuteration, detergent screening and guidelines for detergent selection. Although deuterated detergents are relatively expensive and not always commercially available due to challenges associated with their chemical synthesis, they will continue to play important roles in structural and functional studies of membrane proteins, especially using solution state NMR. PMID- 26906949 TI - Red exophytic mass of the maxillary anterior gingiva. PMID- 26906950 TI - Immunohistochemical expression of keratins 6, 7, 8, 14, 16, 18, 19, and MNF-116 pancytokeratin in primary and metastatic melanoma of the head and neck. AB - OBJECTIVE: To investigate the immunohistochemical expression (IHCE) of selected keratins in primary cutaneous and mucosal melanoma (pM), and metastatic melanoma (metsM) of the head and neck and to compare their expression to a group of undifferentiated/poorly differentiated tumors of the same anatomic region. STUDY DESIGN: IHCE of K6, K7, K8, K14, K16, K18, and K19 were studied in 29 melanomas and 70 cases of non-melanoma tumors of the same anatomic region (neuroendocrine carcinoma, neuroblastoma, olfactory neuroblastoma, sinonasal undifferentiated carcinoma, undifferentiated nasopharyngeal carcinoma, anaplastic large cell lymphoma, poorly differentiated squamous cell carcinoma (PDSCC), and Ewing sarcoma). MNF-116 pancytokeratin was investigated in melanoma. RESULTS: All studied keratins, except K6, were expressed in melanoma. IHCE of MNF-116, K8, and K18 was higher in metsM compared with pM. K14 and K16 expression was highest in PDSCC. CONCLUSIONS: metsM expresses keratins more than pM, specifically K8, K18, and MNF-116. Keratin positivity in an undifferentiated or poorly differentiated neoplasm does not necessarily exclude the diagnosis of melanoma. PMID- 26906951 TI - Changes of choroidal structure after corticosteroid treatment in eyes with Vogt Koyanagi-Harada disease. AB - AIMS: To report the changes of the choroidal structure in the enhanced depth imaging optical coherence tomographic (EDI-OCT) images after high-dose corticosteroid treatment for acute Vogt-Koyanagi-Harada (VKH) disease. METHODS: Retrospective, observational case series. Thirty-four eyes of 17 patients with acute VKH disease were examined by EDI-OCT before, and 1, 4 and 52 weeks after the treatment. The EDI-OCT images were binarised by ImageJ, a publicly accessible software. The luminal, stromal and total choroidal areas and ratio of luminal/stromal area (L/S ratio) were measured in the subfoveal choroid of 1500 um width. The area of the peripapillary atrophy (PPA) was measured in the fundus photographs at 1 and 52 weeks. For statistical analyses, a generalised estimating equation method was used to eliminate the effect of within-subject intereye correlations. RESULTS: Before treatment, the EDI-OCT images could not be binarised because of poor image quality in most of the cases. After treatment, the luminal, stromal and total choroidal areas were significantly decreased during the follow-up period (all p<0.05). The L/S ratio significantly fluctuated over time (p=0.0201), and was significantly lower at 4 weeks than at 1 week (p=0.0158). The L/S ratio at 1 week was significantly correlated with increase in the PPA area, subsequent chronic recurrences and total dose of corticosteroid (p<0.0001, p=0.0006, p=0.0037, respectively). CONCLUSIONS: The L/S ratio measured by binarisation of EDI-OCT images was predictive factor for the progression of PPA, subsequent chronic recurrences and total dose of corticosteroid, and may serve as a marker for degree of choroidal inflammation in the VKH disease. PMID- 26906952 TI - Preserved visual function in retinal dystrophy due to hypomorphic RPE65 mutations. AB - BACKGROUND/AIMS: To present detailed phenotypic and molecular findings in four patients from four families with atypical, mild, recessive RPE65-related retinal dystrophy and discuss potential implications for gene replacement therapy. METHODS: Four patients from four families with early onset retinal dystrophy underwent clinical examination, retinal imaging and electrophysiological testing. Bidirectional Sanger sequencing of all exons and intron-exon boundaries of RPE65 was performed. RESULTS: All patients presented with nyctalopia in early childhood but demonstrated a mild phenotype with good visual acuity until at least 19 years of age. All had generalised retinal dysfunction on electroretinography. Central macular thickness on optical coherence tomography was preserved in those patients with good visual acuity. One patient had extensive white dots throughout the retina reminiscent of fundus albipunctatus with electrophysiological evidence of partial recovery of rod function after prolonged dark adaptation. Sanger sequencing identified RPE65 mutations in all patients including three missense variants likely to represent hypomorphic alleles. CONCLUSIONS: Hypomorphic mutations of RPE65 are associated with mild disease in childhood with preservation of good visual acuity into adulthood; they may in rare cases be associated with a flecked retina appearance similar to fundus albipunctatus. The presence of normal visual acuity in patients with hypomorphic mutations in RPE65 suggests that efficiency of transduction may not be the limiting factor in improving visual acuity in trials of gene replacement therapy. Rather, it suggests that for optimal recovery of visual acuity gene replacement therapy may need to be given much earlier in childhood. PMID- 26906953 TI - Exceptional performance of photoelectrochemical water oxidation of single-crystal rutile TiO2 nanorods dependent on the hole trapping of modified chloride. AB - It is highly desired to effectively trap photogenerated holes for efficient photoelectrochemical (PEC) water oxidation to evolve O2 on oxide semiconductors. Herein, it is found for the first time mainly based on the time-resolved- and atmosphere-controlled- surface photovoltage responses that the modified chloride would effectively trap photogenerated holes so as to prolong the charge lifetime and hence promote charge separation of single-crystal rutile TiO2 nanorods. Its strong capacity to trap holes, comparable to the widely-used methanol and Co(II) phosphate, is well responsible for the exceptional photoactivities for PEC water oxidation to evolve O2 on rutile nanorods with a proper amount of chloride modified, about 2.5-time high as that on the resulting anatase nanoparticles, even 10-time if the surface area is considered. Moreover, it is suggested that the hole trapping role of chemically-adsorbed chloride is related to its lonely pair electrons, and to the subsequently-produced intermediate Cl atoms with proper electronegativity for evolving O2. Interestingly, this finding is also applicable to the chloride-modified anatase TiO2. This work will provide a feasible strategy to design high-activity nanostructured semiconductor photoanodes for PEC water oxidation, even for overall water splitting. PMID- 26906954 TI - Returning to the fold. PMID- 26906955 TI - Toxicity of organometal halide perovskite solar cells. PMID- 26906956 TI - Spintronics: Chiral damping. PMID- 26906957 TI - Molecular thermopower: Feeling the squeeze. PMID- 26906958 TI - Arterial calcification: Conscripted by collagen. PMID- 26906959 TI - Stem cell reprogramming: A 3D boost. PMID- 26906960 TI - Material Witness: The Roman melting pot. PMID- 26906961 TI - Electromagnetic toroidal excitations in matter and free space. AB - The toroidal dipole is a localized electromagnetic excitation, distinct from the magnetic and electric dipoles. While the electric dipole can be understood as a pair of opposite charges and the magnetic dipole as a current loop, the toroidal dipole corresponds to currents flowing on the surface of a torus. Toroidal dipoles provide physically significant contributions to the basic characteristics of matter including absorption, dispersion and optical activity. Toroidal excitations also exist in free space as spatially and temporally localized electromagnetic pulses propagating at the speed of light and interacting with matter. We review recent experimental observations of resonant toroidal dipole excitations in metamaterials and the discovery of anapoles, non-radiating charge current configurations involving toroidal dipoles. While certain fundamental and practical aspects of toroidal electrodynamics remain open for the moment, we envision that exploitation of toroidal excitations can have important implications for the fields of photonics, sensing, energy and information. PMID- 26906962 TI - Erratum: The surface science of nanocrystals. PMID- 26906963 TI - Corrigendum: Activating and optimizing MoS2 basal planes for hydrogen evolution through the formation of strained sulphur vacancies. PMID- 26906965 TI - Autoimmune encephalitis: paving the way for early diagnosis. PMID- 26906966 TI - Encephalitis: raising awareness and collaborating in research. PMID- 26906967 TI - Quantum Local Monomer IR Spectrum of Liquid D2O at 300 K from 0 to 4000 cm(-1) Is in Near-Quantitative Agreement with Experiment. AB - The local monomer model is applied, with ab initio potential energy and dipole moment surfaces, to a calculation of the IR spectrum of liquid D2O at 300 K, over the spectral range 0 to 4000 cm(-1). The spectrum is an incoherent superposition of spectra of many monomers over snapshots of a molecular dynamics trajectory, where both intramolecular and intermolecular coupling in each monomer is treated. The comparison to experiment shows an unprecedented level of agreement for the stretch, bend, and libration bands and also the bend+libration and stretch+bend combination bands. This indicates that the incoherent approach captures much of the dynamics underlying the spectrum, provided monomer couplings are considered. The calculated spectrum is compared to the recently calculated IR spectrum of H2O, using the same method and potential energy and dipole moment surfaces, and shifts relative to that spectrum are presented and discussed. PMID- 26906968 TI - Cytotoxic biomonitored study of Euphorbia umbellata (Pax) Bruyns. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Euphorbia umbellata latex (sap) has normally been used in folk medicine in southern Brazil to treat different types of cancers. AIM OF STUDY: To carry out a biomonitored investigation of partitioned latex using in vitro assay, to identify the main mechanisms related with the action of the most active fraction as well as to develop a phytochemical study with this material. MATERIALS AND METHODS: Biological screening was performed with hexane, chloroform, ethyl acetate and methanol fractions from the latex of E. umbellata using MTT, trypan blue, and neutral red assays to determine the cytotoxicity against HRT-18, HeLa and Jurkat cells and flow cytometry, DNA quantification, acridine orange and Hoechst 33342 staining to investigate mechanisms of action for the hexane extract. The phytochemical study of the hexane fraction was performed by chromatographic procedures and the substances were identified by NMR analysis. The isolated terpenes were evaluated using MTT to determine the cytotoxicity against Jurkat cells. RESULTS: All the fractions presented concentration and time dependent cytotoxicity. The hexane fraction showed the highest cytotoxicity; whereas the Jurkat cell was the lineage with the highest sensitivity (IC50 1.87ug/mL). Fragmentation of DNA and apoptosis are two mechanisms related with the toxicity of hexane fraction. The hexane fraction arrested the cell cycle in the G0/G1 phase, and the selectivity index was 4.30. Phytochemical study of the hexane fraction led to isolation of euphol (main compound) and germanicol acetate. Both substances demonstrated some slight cytotoxic activity against Jurkat cells after 72h; however the activity was minimal compared to vincristine (anticancer standard drug). CONCLUSION: The current research proves that the fractions of the latex from E. umbellata have a cytotoxic effect against three different cancer cells lines. The hexane fraction showed high in vitro cytotoxic effects against Jurkat cells demonstrating that the effect may be due to non-polar constituents. The two isolated terpenes (euphol and germanicol acetate) showed poor cytotoxic activity indicating that the anticancer properties of the extract may be caused by other substances present in the hexane fraction. PMID- 26906964 TI - A clinical approach to diagnosis of autoimmune encephalitis. AB - Encephalitis is a severe inflammatory disorder of the brain with many possible causes and a complex differential diagnosis. Advances in autoimmune encephalitis research in the past 10 years have led to the identification of new syndromes and biomarkers that have transformed the diagnostic approach to these disorders. However, existing criteria for autoimmune encephalitis are too reliant on antibody testing and response to immunotherapy, which might delay the diagnosis. We reviewed the literature and gathered the experience of a team of experts with the aims of developing a practical, syndrome-based diagnostic approach to autoimmune encephalitis and providing guidelines to navigate through the differential diagnosis. Because autoantibody test results and response to therapy are not available at disease onset, we based the initial diagnostic approach on neurological assessment and conventional tests that are accessible to most clinicians. Through logical differential diagnosis, levels of evidence for autoimmune encephalitis (possible, probable, or definite) are achieved, which can lead to prompt immunotherapy. PMID- 26906969 TI - Gastroprotective potential of Pentahydroxy flavone isolated from Madhuca indica J. F. Gmel. leaves against acetic acid-induced ulcer in rats: The role of oxido inflammatory and prostaglandins markers. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Madhuca indica J. F. Gmel. (Sapotaceae) has shown antioxidant, anti-inflammatory, analgesic, anti-diabetic and hepatoprotective potential. It has been traditionally used as laxative, tonic, anti-burn, anti earthworm, wound healing and headache. AIM OF THE STUDY: To investigate the efficacy and possible mechanism of Madhuca indica J. F. Gmel. leaves methanolic extract (MI-ALC) and its isolated chloroform fraction (D3) against experimental induced gastric ulcers. MATERIALS AND METHODS: D3 was isolated from MI-ALC, well characterized (HPTLC, FT-IR, (1)H-NMR and LC-MS) and evaluated for its gastroprotective activity by using acetic acid induced ulcer in male Wistar rats (150-200g). D3 (2.5, 5 and 10mg/kg, p.o.) were administered for the period of 14 days. At the end of treatment, rats were sacrificed to collect the stomach sample for evaluation of antioxidant (SOD, GSH, and MDA) enzyme, oxido-inflammatory (TNF alpha, IL-1, iNOs) and prostaglandins (COX-II) markers by using RT-PCR. RESULTS: The structure and molecular weight (MW) of the isolated compound (D3) were confirmed by 1D and 2D spectral data and characterized as 3,5,7,3',4' Pentahydroxy flavone with MW C15H10O7. Administration of 3,5,7,3',4'-Pentahydroxy flavone (5 and 10mg/kg) significantly and dose-dependently inhibited (P<0.01 and P<0.001) acetic acid induced an alteration in the antioxidant enzyme. It also significantly and dose-dependently down-regulated gastric oxido-inflammatory and prostaglandins markers. Histopathological aberration induced in the stomach also attenuated by 3,5,7,3',4'-Pentahydroxy flavone treatment. CONCLUSION: Finding of present investigation suggests that MI-ALC possessed potent antiulcer activity due to the presence of 3,5,7,3',4'-Pentahydroxy flavone via its oxido inflammatory and prostaglandins modulatory potential. PMID- 26906970 TI - Randomised controlled trial using smartphone website vs leaflet to support antenatal perineal massage practice for pregnant women. AB - BACKGROUND: In Japan, the rate of pregnant women who practice antenatal perineal massage was only 15.1%. AIM: The aim of this study was to develop and evaluate a smartphone website and a leaflet to support antenatal perineal massage practice for primiparous women. METHODS: In a randomised control trial, 161 primiparous women were randomly assigned to a smartphone website group (n=81) or a leaflet group (n=80). Data analysis were by per protocol analysis and intention to treat analysis. FINDINGS: Of the 161 women participants, 47 in the smartphone website group and 49 in the leaflet group completed all questionnaires. Primary outcome was continuance rate (three times a week over a three week period) of antenatal perineal massage practice. The rates by a per protocol analysis were 51.1% in the smartphone website group and 51.0% in the leaflet group, respectively. There was no significant difference between the groups. Moreover, the rates by an intention to treat analysis were 29.6% in the smartphone website group and 31.3% in the leaflet group, respectively. There was also no significant difference between the groups. There were no significant differences in the evaluation of perineal massage, childbirth self-efficacy, satisfaction with efforts towards childbirth, and perineal outcomes following childbirth which were measured as secondary outcomes between the groups. CONCLUSION: There was no significant difference in continuance rate of antenatal perineal massage practice between those using a smartphone website and those with a leaflet, however, the rate was better than no instructions. PMID- 26906971 TI - Carotid Stenosis in Cardiac Surgery-No Difference in Postoperative Outcomes. AB - BACKGROUND: Debate over revascularization of asymptomatic carotid stenosis before cardiac surgery is ongoing. In this study, we analyze cardiac surgery outcomes in patients with asymptomatic carotid stenosis at a single hospital. METHODS: In this study, 1,781 patients underwent cardiac surgery from January 2012 to June 2013; 1,357 with preoperative screening carotid duplex were included. Patient demographics, comorbidities, degree of stenosis, postoperative complications, and mortality were evaluated. Chi-square test and logistic regression analysis were performed. RESULTS: Asymptomatic stenosis was found in 403/1,357 patients (29.7%; 355 moderate and 48 severe). Patients with stenosis, compared with those without, were older (71.7 +/- 11 vs. 66.3 +/- 12 years; p < 0.01). Females were more likely to have stenosis (odd ratio, = 1.7; 95% confidence interval, 1.4-2.2); however, patients were predominantly male in both groups. There were no significant differences in the rates of mortality and postoperative complications, including stroke and transient ischemic attack (TIA). Postoperative TIA occurred in 3/1,357(0.2%); only one had moderate stenosis. Inhospital stroke occurred in 21/1,357 (1.5%) patients; stroke rates were 2.3% (8/355) with moderate stenosis and 2.1% (1/48) severe stenosis. There were 59/1,357 (4.3%) deaths; patients with stenosis had a mortality rate of 4.2% (17/403); however, no postoperative stroke lead to death. Multivariable logistic regression analysis with adjustment for age, gender, race, comorbidities, and postoperative complications did not show an impact of carotid stenosis on postoperative mortality and development of stroke after cardiac surgery. CONCLUSION: This study suggests that patients with asymptomatic carotid stenosis undergoing cardiac surgery are not at increased risk of postoperative complications and mortality; thus, prophylactic carotid revascularization may not be indicated. PMID- 26906972 TI - Respiratory System Function in Patients after Aortic Valve Replacement through Right Anterior Minithoracotomy. AB - Background The aim of the study was to analyze respiratory system function after minimally invasive aortic valve replacement through right anterior minithoracotomy (RAT-AVR). Methods An observational study of 187 patients electively scheduled for RAT-AVR between January 2010 and December 2013. Pulmonary complications were analyzed and spirometry examinations were performed preoperatively, 1 week, 1 month, and 3 months after surgery. Results Hospital mortality was 1.1%. A double-lumen intratracheal tube was used in 88.2% and single-lumen intratracheal tube was used in 11.8% of patients. Pulmonary complications occurred in 10.8% of the patients. Prolonged (>24 hours) mechanical ventilation time was present in five patients (2.7%). The reasons were stroke (n = 1), perioperative myocardial infarction (n = 2), and pneumothorax (n = 2). Right pleural effusion, which occurred in 7.7% (n = 14) of patients, was the most frequent respiratory system complication. One week after surgery, the spirometry parameters decreased in comparison to the preoperative period, then after 3 months statistically significant improvement occurred; however, the spirometry parameters still had not returned to preoperative values. Multivariable median regression analysis shows that the presence of chronic obstructive pulmonary disease and pulmonary complications were associated with lower values of forced expiratory volume in 1 second after surgery. There was no statistically significant difference regarding spirometry values or incidence of pulmonary complications after surgery between patients in whom single-lung or double-lung ventilation was applied. Conclusion Pulmonary functional status measured with spirometry parameters was diminished after RAT-AVR surgery. Single-lung ventilation did not result in a higher rate of respiratory complications after RAT-AVR surgery. PMID- 26906973 TI - Simultaneous knockdown of uPA and MMP9 can reduce breast cancer progression by increasing cell-cell adhesion and modulating EMT genes. AB - In cancer progression, proteolytic enzymes like serine proteases and metalloproteinases degrade the basement membrane enabling the tumor cells to invade the adjacent tissues. Thus, invasion and metastasis are augmented by these enzymes. Simultaneous silencing of uPA and MMP9 in breast cancer cells decreased the wound healing, migratory, invasive and adhesive capacity of the cells. After simultaneous down regulation, cells were seen to be arrested in the cell cycle. There was a remarkable increase in the expression of cell to cell adhesion molecule E-cadherin, and decrease in Vimentin and Snail expression. In addition, there was a significant decrease in the expression of the stem cell marker Oct-4. In the breast tumor samples it has been observed that, tumors, expressing higher level of uPA and MMP9, express less amount of E-cadherin. It has also been observed that few tumors also show, Vimentin positive in the ductal epithelial area. Thus, our model can help for checking the aggressive tumor invasion by blocking of uPA and MMP9. Our present observations also give the concept of the presence of aggressive epithelial cells with mesenchymal nature in the tumor micro-environment, altering the expression of EMT genes. PMID- 26906974 TI - High prevalence of secondary factors for bone fragility in patients with a recent fracture independently of BMD. AB - In this study, we demonstrate a high prevalence of secondary factors in patients with a recent fracture independently of bone mineral density (BMD). Our results suggest that patients with a recent fracture should be screened for secondary factors for bone fragility regardless of BMD values. INTRODUCTION: Secondary factors for bone fragility are common in patients with osteoporosis who have sustained a fracture. The majority of fragility fractures occurs, however, in patients with osteopenia, and it is not known whether secondary factors may contribute to fracture risk in these patients or in those with normal BMD. METHODS: Prospective cohort study evaluating the prevalence of secondary factors for bone fragility in consecutive patients referred to our fracture liaison service from June 2012 to June 2014 after a recent fracture. RESULTS: Seven hundred nine patients were included, 201 (28 %) with osteoporosis, 391 (55 %) with osteopenia and 117 (17 %) with normal BMD. Mean age was 66.0 +/- 9.8 years, 504 (73 %) were women and 390 (57 %) had one or more underlying secondary factor. Evaluation of clinical risk factors using fracture risk assessment tool (FRAX) identified 38 % of patients with >=1 secondary factor including smoking (18 %), excessive alcohol use (12 %), glucocorticoid use (12 %) and rheumatoid arthritis (3 %). Laboratory investigations revealed chronic kidney disease in 13 %, monoclonal gammopathy also in 13 % and primary or secondary hyperparathyroidism in 1 and 6 %, respectively. Secondary factors for bone fragility were equally prevalent in patients with osteoporosis, osteopenia or normal BMD. CONCLUSIONS: Our findings demonstrate a high prevalence of secondary factors for bone fragility in patients who have sustained a recent fracture, independently of BMD. The significant number of documented factors, which were treatable, suggest that patients who sustained a fracture should be screened for secondary factors for bone fragility regardless of BMD values to optimise secondary fracture prevention. PMID- 26906975 TI - Using Multi-objective Optimization to Identify Dynamical Network Biomarkers as Early-warning Signals of Complex Diseases. AB - Biomarkers have gained immense scientific interest and clinical value in the practice of medicine. With unprecedented advances in high-throughput technologies, research interest in identifying novel and customized disease biomarkers for early detection, diagnosis, or drug responses is rapidly growing. Biomarkers can be identified in different levels of molecular biomarkers, networks biomarkers and dynamical network biomarkers (DNBs). The latter is a recently developed concept which relies on the idea that a cell is a complex system whose behavior is emerged from interplay of various molecules, and this network of molecules dynamically changes over time. A DNB can serve as an early warning signal of disease progression, or as a leading network that drives the system into the disease state, and thus unravels mechanisms of disease initiation and progression. It is therefore of great importance to identify DNBs efficiently and reliably. In this work, the problem of DNB identification is defined as a multi-objective optimization problem, and a framework to identify DNBs out of time-course high-throughput data is proposed. Temporal gene expression data of a lung injury with carbonyl chloride inhalation exposure has been used as a case study, and the functional role of the discovered biomarker in the pathogenesis of lung injury has been thoroughly analyzed. PMID- 26906976 TI - Aerobic mitochondria of parasitic protists: Diverse genomes and complex functions. AB - In this review the main features of the mitochondria of aerobic parasitic protists are discussed. While the best characterized organelles are by far those of kinetoplastid flagellates and Plasmodium, we also consider amoebae Naegleria and Acanthamoeba, a ciliate Ichthyophthirius and related lineages. The simplistic view of the mitochondrion as just a power house of the cell has already been abandoned in multicellular organisms and available data indicate that this also does not apply for protists. We discuss in more details the following mitochondrial features: genomes, post-transcriptional processing, translation, biogenesis of iron-sulfur complexes, heme metabolism and the electron transport chain. Substantial differences in all these core mitochondrial features between lineages are compatible with the view that aerobic protists harbor organelles that are more complex and flexible than previously appreciated. PMID- 26906978 TI - Giant-pulse Nd:YVO4 microchip laser with MW-level peak power by emission cross sectional control. AB - We present a giant-pulse generation laser realized by the emission cross-section control of a gain medium in a passively Q-switched Nd:YVO4 microchip laser with a Cr4+:YAG saturable absorber. Up to 1.17 MW peak power and 1.03 mJ pulse energy were obtained with a 100 Hz repetition rate. By combining the Nd:YVO4 crystal with a Sapphire plate, lower temperature difference between a pump region in the gain crystal and a crystal holder was obtained which helped to keep the cavity in stability zone at elevated temperatures and allowed the achievement of the high peak power for this laser system. PMID- 26906979 TI - Focused electromagnetic doughnut pulses and their interaction with interfaces and nanostructures. AB - "The "focused doughnut", a single-cycle electromagnetic perturbation of toroidal topology with inseparable time and spatial dependencies propagates at the speed of light in vacuum, as was shown by Hellwarth and Nouchi in 1996. While normal incidence reflection and refraction of conventional electromagnetic pulses in isotropic media do not lead to polarization changes, "focused doughnut" pulses undergo complex field transformations owing to the toroidal field structure and the presence of longitudinal components. We also demonstrate that "focused doughnuts" can interact strongly with structured media exciting dominant dynamic toroidal dipoles in spherical dielectric particles." PMID- 26906977 TI - Value of delayed duplex ultrasound assessment after endothermal ablation of the great saphenous vein. AB - OBJECTIVE: Endothermal ablation (ETA) of the great saphenous vein (GSV) is associated with a small but definite risk of endothermal heat-induced thrombosis (EHIT) extending into the common femoral vein. Follow-up duplex ultrasound imaging to detect EHIT after ETA is considered standard of care, although the exact timing of duplex ultrasound imaging to detect EHIT after ETA remains unclear. We hypothesized that an additional duplex ultrasound assessment 1 week after ETA would not identify a significant number of patients with EHIT and would significantly increase health care costs. METHODS: This was a retrospective review of consecutive ETA GSV procedures from 2007 to 2014. All patients were evaluated with duplex ultrasound imaging on postprocedure day 1, and 79% of patients underwent a second ultrasound assessment 1 week postprocedure. EHIT was considered present when proximal GSV closure progressed to level >=4, based on a six-tier classification system. RESULTS: From January 1, 2007, until December 31, 2014, 842 patients underwent GSV ETA. Patients with EHIT were more likely to have had a prior deep venous thrombosis (DVT; P = .002) and a larger GSV (P = .006). Forty-three procedures (5.1%) were classified as having EHIT requiring anticoagulation, based on a level >=4 proximal closure level. Of the 43 patients with EHIT, 20 (47%) were found on the initial ultrasound assessment performed 24 hours postprocedure, but 19 patients (44%) with EHIT would not have been identified with a single postoperative ultrasound scan performed 24 hours after intervention. These 19 patients had a level <=3 closure level at the duplex ultrasound scan performed 24 hours postprocedure and progressed to EHIT on the delayed duplex ultrasound scan. Lastly, thrombotic complications in four patients (9%), representing three late DVT and one DVT/pulmonary embolism presenting to another hospital, would not have been identified regardless of the postoperative surveillance strategy. Maximum GSV diameter was the only significant predictor of progression to EHIT on multivariate analysis (P = .007). Based on 2014 United States dollars, the two-ultrasound surveillance paradigm is associated with health care charges of $31,109 per identified delayed venous thromboembolism event. CONCLUSIONS: Delayed duplex ultrasound assessment after ETA of the GSV comes with associated health care costs but does yield a significant number of patients with progression to EHIT. Better understanding of the timing, risk factors, and significance of EHIT is needed to cost-effectively care for patients after ETA for varicose veins. PMID- 26906980 TI - Linearly frequency-modulated pulsed single-frequency fiber laser at 1083 nm. AB - A linearly frequency-modulated, actively Q-switched, single-frequency ring fiber laser based on injection seeding from an ultra-short cavity is demonstrated at 1083 nm. A piezoelectric transducer is employed to obtain linearly frequency modulating performance and over 1.05 GHz frequency-tuning range is achieved with a modulating frequency reaching tens of kilohertz. A maximum peak power of the stable output pulse is over 3.83 W during frequency-modulating process. This type of pulsed fiber laser provides a promising candidate for coherent LIDAR in the measurement of thermosphere. PMID- 26906981 TI - Generation of photonic orbital angular momentum superposition states using vortex beam emitters with superimposed gratings. AB - An integrated approach to produce photonic orbital angular momentum (OAM) superposition states with arbitrary OAM spectrum has been demonstrated. Superposition states between two vector OAM modes have been achieved by integrating a superimposed angular grating in one silicon micro-ring resonator, with each mode having near equal weight. The topological charge difference between the two compositional OAM modes is determined by the difference between the numbers of elements in the two original gratings being superimposed, while the absolute values of the topological charge can be changed synchronously by switching WGM resonant wavelengths. This novel approach provides a scalable and flexible source for the OAM-based quantum information and optical manipulation applications. PMID- 26906982 TI - Fast phase processing in off-axis holography by CUDA including parallel phase unwrapping. AB - We present parallel processing implementation for rapid extraction of the quantitative phase maps from off-axis holograms on the Graphics Processing Unit (GPU) of the computer using computer unified device architecture (CUDA) programming. To obtain efficient implementation, we parallelized both the wrapped phase map extraction algorithm and the two-dimensional phase unwrapping algorithm. In contrast to previous implementations, we utilized unweighted least squares phase unwrapping algorithm that better suits parallelism. We compared the proposed algorithm run times on the CPU and the GPU of the computer for various sizes of off-axis holograms. Using the GPU implementation, we extracted the unwrapped phase maps from the recorded off-axis holograms at 35 frames per second (fps) for 4 mega pixel holograms, and at 129 fps for 1 mega pixel holograms, which presents the fastest processing framerates obtained so far, to the best of our knowledge. We then used common-path off-axis interferometric imaging to quantitatively capture the phase maps of a micro-organism with rapid flagellum movements. PMID- 26906983 TI - Signal-to-noise criterion for free-propagation imaging techniques at free electron lasers and synchrotrons. AB - We propose a signal-to-noise criterion which predicts whether a feature of a given size and scattering strength, placed inside a larger object, can be retrieved with two common X-ray imaging techniques: coherent diffraction imaging and projection microscopy. This criterion, based on how efficiently these techniques detect the scattered photons and validated through simulations, shows in general that projection microscopy can resolve smaller phase differences and features than coherent diffraction imaging. Our criterion can be used to design optimized imaging experiments and perform feasibility studies for sensitive biological materials in free-electron lasers, where the number of photons per pulse is limited, or in synchrotron experiments, for both techniques. PMID- 26906984 TI - Demodulation of two-shot fringe patterns with random phase shifts by use of orthogonal polynomials and global optimization. AB - We propose a simple and robust phase demodulation algorithm for two-shot fringe patterns with random phase shifts. Based on a smoothness assumption, the phase to be recovered is decomposed into a linear combination of finite terms of orthogonal polynomials, and the expansion coefficients and the phase shift are exhaustively searched through global optimization. The technique is insensitive to noise or defects, and is capable of retrieving phase from low fringe-number (less than one) or low-frequency interferograms. It can also cope with interferograms with very small phase shifts. The retrieved phase is continuous and no further phase unwrapping process is required. The method is expected to be promising to process interferograms with regular fringes, which are common in optical shop testing. Computer simulation and experimental results are presented to demonstrate the performance of the algorithm. PMID- 26906985 TI - Output blue light evaluation for phosphor based smart white LED wafer level packages. AB - This study presents a blue light detector for evaluating the output light of phosphor based white LED package. It is composed of a silicon stripe-shaped photodiode designed and implemented in a 2 MUm BiCMOS process which can be used for wafer level integration of different passive and active devices all in just 5 lithography steps. The final device shows a high selectivity to blue light. The maximum responsivity at 480 nm is matched with the target blue LED illumination. The designed structure have better responsivity compared to simple photodiode structure due to reducing the effect of dead layer formation close to the surface because of implantation. It has also a two-fold increase in the responsivity and quantum efficiency compared to previously similar published sensors. PMID- 26906986 TI - Novel polyimide coated fiber Bragg grating sensing network for relative humidity measurements. AB - A novel relative humidity (RH) sensing network based on ultra-weak fiber Bragg gratings (FBGs) is proposed and demonstrated. Experiment is demonstrated on a 5 serial ultra-weak FBGs sensing network chopped from a fiber array with 1124 FBGs. Experimental results show that the corresponding RH sensitivity varies from 1.134 to 1.832 pm/%RH when ambient environmental RH changes from 23.8%RH to 83.4%RH. The low-reflectance FBGs and time-division multiplexing (TDM) technology makes it possible to multiplex thousands of RH sensors in single optical fiber. PMID- 26906987 TI - On the generation of grooves on crystalline silicon irradiated by femtosecond laser pulses. AB - Irradiation of crystalline silicon with femtosecond laser pulses produces a variety of quasi-periodic surface structures, among which sub-wavelength ripples creation is largely studied. Here we report an experimental investigation and a theoretical interpretation focusing on the seldom considered issue of quasi periodic, micron spaced grooves formation. We characterize the morphological evolution of the grooves generation and experimentally single out the variation of the threshold fluence for their formation with the number of pulses N, while typical ripples simultaneously produced in the irradiated area are always considered for comparison. Our experimental findings evidence a power law dependence of the threshold fluence on the number of pulses both for ripples and grooves formation, typical of an incubation behavior. The incubation factor and single pulse threshold are (0.76 +/- 0.04) and (0.20 +/- 0.04) J/cm2 for ripples and (0.84 +/- 0.03) and (0.54 +/- 0.08) J/cm2 for grooves, respectively. Surface-scattered wave theory, which allows modeling irradiation with a single pulse on a rough surface, is exploited to interpret the observed structural modification of the surface textures. A simple, empirical scaling approach is proposed associating the surface structures generated in multiple pulse experiments with the predictions of the surface-scattered wave theory, at laser fluencies around the grooves formation threshold. This, in turn, allows proposing a physical mechanism interpreting the grooves generation as well as the coexistence and relative prominence of grooves and ripples in the irradiated area. PMID- 26906988 TI - Free-space-coupled superconducting nanowire single-photon detectors for infrared optical communications. AB - This paper describes the construction of a cryostat and an optical system with a free-space coupling efficiency of 56.5% +/- 3.4% to a superconducting nanowire single-photon detector (SNSPD) for infrared quantum communication and spectrum analysis. A 1K pot decreases the base temperature to T = 1.7 K from the 2.9 K reached by the cold head cooled by a pulse-tube cryocooler. The minimum spot size coupled to the detector chip was 6.6 +/- 0.11 um starting from a fiber source at wavelength, lambda = 1.55 um. We demonstrated photon counting on a detector with an 8 * 7.3 um2 area. We measured a dark count rate of 95 +/- 3.35 kcps and a system detection efficiency of 1.64% +/- 0.13%. We explain the key steps that are required to improve further the coupling efficiency. PMID- 26906989 TI - Silver metaphosphate glass wires inside silica fibers--a new approach for hybrid optical fibers. AB - Phosphate glasses represent promising candidates for next-generation photonic devices due to their unique characteristics, such as vastly tunable optical properties, and high rare earth solubility. Here we show that silver metaphosphate wires with bulk optical properties and diameters as small as 2 um can be integrated into silica fibers using pressure-assisted melt filling. By analyzing two types of hybrid metaphosphate-silica fibers, we show that the filled metaphosphate glass has only negligible higher attenuation and a refractive index that is identical to the bulk material. The presented results pave the way towards new fiber-type optical devices relying on metaphosphate glasses, which are promising materials for applications in nonlinear optics, sensing and spectral filtering. PMID- 26906990 TI - Amplitude image processing by diffractive optics. AB - In contrast to the standard digital image processing, which operates over the detected image intensity, we propose to perform amplitude image processing. Amplitude processing, like low pass or high pass filtering, is carried out using diffractive optics elements (DOE) since it allows to operate over the field complex amplitude before it has been detected. We show the procedure for designing the DOE that corresponds to each operation. Furthermore, we accomplish an analysis of amplitude image processing performances. In particular, a DOE Laplacian filter is applied to simulated astronomical images for detecting two stars one Airy ring apart. We also check by numerical simulations that the use of a Laplacian amplitude filter produces less noisy images than the standard digital image processing. PMID- 26906991 TI - Stimulated Raman scattering in AsSe2-As2S5 chalcogenide microstructured optical fiber with all-solid core. AB - The effects of stimulated Raman scattering (SRS) is demonstrated in chalcogenide microstructured optical fiber (MOF) with all-solid AsSe2 core and As2S5 cladding. The first-order Raman Stokes wave is investigated in the MOFs with different core diameters pumped by the picosecond pulses at 1958 nm. The maximum conversion efficiency of -15.0 dB from the pump to first-order Raman Stokes wave is obtained in the MOF with the core diameter of 2.6 MUm. The conversion efficiency decreases when the core diameter deviates from 2.6 MUm. When the fiber core is larger, the effective nonlinearity is decreased. When the fiber core is smaller, the mode field is difficult to be confined in the core. The walk-off length between the pump and Stokes wave is crucial to the process of SRS according to the analysis of the experimental data. The Raman effects are simulated numerically. The simulated results can agree well with the experiments. It is the first time to demonstrate the Raman effect in AsSe2-As2S5 MOF, to the best of our knowledge. PMID- 26906992 TI - Rf-modulation of mid-infrared distributed feedback quantum cascade lasers. AB - We present the electrical and optical characterization and theoretical modeling of the transient behavior of regular 4.5-MUm single-mode emitting distributed feedback (DFB) quantum cascade lasers (QCLs). Low residual capacitance together with a high-frequency optimized three-terminal coplanar waveguide configuration leads to modulation frequencies up to 23.5 GHz (optical) and 26.5 GHz (electrical), respectively. A maximum 3-dB cut-off value of 6.6 GHz in a microwave rectification scheme is obtained, with a significant increase in electrical modulation bandwidth when increasing the DC-current for the entire current range of the devices. Optical measurements by means of FTIR-spectroscopy and a heterodyne beating experiment reveal the presence of a resonance peak, due to coupling of the lasing DFB- with its neighboring below-threshold Fabry-Perot (FP-)mode, when modulating around the cavity roundtrip frequency. This resonance is modeled by a 2-mode Maxwell-Bloch formalism. It enhances only one sideband and consequently leads to the first experimental observation of the single-sideband regime in such kind of devices. PMID- 26906993 TI - Photon pair generation from compact silicon microring resonators using microwatt level pump powers. AB - Microring resonators made from silicon are becoming a popular microscale device format for generating photon pairs at telecommunications wavelengths at room temperature. In compact devices with a footprint less than 5 * 10(-4) mm2, we demonstrate pair generation using only a few microwatts of average pump power. We discuss the role played by important parameters such as the loss, group-velocity dispersion and the ring-waveguide coupling coefficient in finding the optimum operating point for silicon microring pair generation. Silicon photonics can be fabricated using deep ultraviolet lithography wafer-scale fabrication processes, which is scalable and cost-effective. Such small devices and low pump power requirements, and the side-coupled waveguide geometry which uses an integrated waveguide, could be beneficial for future scaled-up architectures where many pair generation devices are required on the same chip. PMID- 26906994 TI - Fundamental limits to optical response in absorptive systems. AB - At visible and infrared frequencies, metals show tantalizing promise for strong subwavelength resonances, but material loss typically dampens the response. We derive fundamental limits to the optical response of absorptive systems, bounding the largest enhancements possible given intrinsic material losses. Through basic conservation-of-energy principles, we derive geometry-independent limits to per volume absorption and scattering rates, and to local-density-of-states enhancements that represent the power radiated or expended by a dipole near a material body. We provide examples of structures that approach our absorption and scattering limits at any frequency; by contrast, we find that common "antenna" structures fall far short of our radiative LDOS bounds, suggesting the possibility for significant further improvement. Underlying the limits is a simple metric, |chi|2/Im chi for a material with susceptibility chi, that enables broad technological evaluation of lossy materials across optical frequencies. PMID- 26906995 TI - Correlated photon pair generation in AlGaAs nanowaveguides via spontaneous four wave mixing. AB - We demonstrate a source of correlated photon pairs which will have applications in future integrated quantum photonic circuits. The source utilizes spontaneous four-wave mixing (SFWM) in a dispersion-engineered nanowaveguide made of AlGaAs, which has merits of negligible two-photon absorption and low spontaneous Raman scattering (SpRS). We observe a coincidence-to-accidental (CAR) ratio up to 177, mainly limited by propagation losses. Experimental results agree well with theoretical predictions of the SFWM photon pair generation and the SpRS noise photon generation. We also study the effects from the SpRS, propagation losses, and waveguide lengths on the quality of our source. PMID- 26906996 TI - Spin-controlled orbital motion in tightly focused high-order Laguerre-Gaussian beams. AB - Spin angular momentum can contribute to both optical force and torque exerted on spheres. Orbit rate of spheres located in tightly focused LG beams with the same azimuthal mode index l is spin-controlled due to spin-orbit coupling. Laguerre Gaussian beams with high-order azimuthal mode are used here to study the orbit rate of dielectric spheres. Orbit rates of spheres with varying sizes and refravtive indices are investigated as well as optical forces acting on spheres in LG beams with different azimuthal modes. These results would be much helpful to investigation on optical rotation and transfer of spin and orbital angular momentum. PMID- 26906997 TI - PMD tolerant nonlinear compensation using in-line phase conjugation. AB - In this paper, we numerically investigate the impact of polarisation mode dispersion on the efficiency of compensation of nonlinear transmission penalties for systems employing one of more inline phase conjugation devices. We will show that reducing the spacing between phase conjugations allows for significantly improved performance in the presence polarisation mode dispersion or a significant relaxation in the acceptable level of polarization mode dispersion. We show that these results are consistent with previously presented full statistical analysis of nonlinear transmission appropriately adjusted for the reduced section length undergoing compensation. PMID- 26906998 TI - Evaluation of absolute form measurements using a tilted-wave interferometer. AB - Tilted-wave interferometry is a promising measurement technique for the highly accurate measurement of aspheres and freeform surfaces. However, the interferometric fringe evaluation of the sub-apertures causes unknown patch offsets, which currently prevent this measurement technique from providing absolute measurements. Simple strategies, such as constructing differences of optical path length differences (OPDs) or ignoring the piston parameter, can diminish the accuracy resulting from the absolute form measurement. Additional information is needed instead; in this paper, the required accuracy of such information is explored in virtual experiments. Our simulation study reveals that, when one absolute OPD is known within a range of 500 nm, the accuracy of the final measurement result is significantly enhanced. PMID- 26906999 TI - Photonic lantern adaptive spatial mode control in LMA fiber amplifiers. AB - We demonstrate adaptive-spatial mode control (ASMC) in few-moded double-clad large mode area (LMA) fiber amplifiers by using an all-fiber-based photonic lantern. Three single-mode fiber inputs are used to adaptively inject the appropriate superposition of input modes in a multimode gain fiber to achieve the desired mode at the output. By actively adjusting the relative phase of the single-mode inputs, near-unity coherent combination resulting in a single fundamental mode at the output is achieved. PMID- 26907000 TI - Application of mid-infrared pulses for quasi-phase-matching of high-order harmonics in silver plasma. AB - We demonstrate the quasi-phase-matching of a group of harmonics generated in Ag multi-jet plasma using tunable pulses in the region of 1160 - 1540 nm and their second harmonic emission. The numerical treatment of this effect includes microscopic description of the harmonic generation, propagation of the pump pulse, and the propagation of the generated harmonics. We obtained more than 30 fold growth of harmonics at the conditions of quasi-phase-matching in the region of 35 nm using eight-jet plasma compared with the case of imperforated plasma. PMID- 26907001 TI - Critical power and clamping intensity inside a filament in a flame. AB - We report on measurements of both the critical power for self-focusing of a Ti: Sapphire 800 nm femtosecond laser and the peak intensity clamped inside a single filament in an ethanol-air flame on an alcohol burner array. By observing the shift of focal position of femtosecond laser pulses, we determine the critical power in the flame to be 2.2 +/- 0.3 GW, which is 4-5 times smaller than the usually quoted one in air. The clamped laser intensity inside the filament is measured to be roughly half of that in air. Our results provide insights into the understanding of femtosecond laser filamentation in flames for practical application of combustion diagnostics. PMID- 26907002 TI - Long range hybrid tube-wedge plasmonic waveguide with extreme light confinement and good fabrication error tolerance. AB - We studied a novel long range hybrid tube-wedge plasmonic (LRHTWP) waveguide consisting of a high index dielectric nanotube placed above a triangular metal wedge substrate. Using comprehensive numerical simulations on guiding properties of the designed waveguide, it is found that extreme light confinement and low propagation loss are obtained due to strong coupling between dielectric nanotube mode and wedge plasmon polariton. Comparing with previous studied hybrid plasmonic waveguides, the LRHTWP waveguide has longer propagation length and tighter mode confinement. In addition, the LRHTWP waveguide is quite tolerant to practical fabrication errors such as variation of the wedge tip angle and the horizontal misalignment between the nanotube and the metal wedge. The proposed LRHTWP waveguide could have many application potentials for various high performance nanophotonic components. PMID- 26907003 TI - Systematic study of thresholdless oscillation in high-beta buried multiple quantum-well photonic crystal nanocavity lasers. AB - Buried multiple-quantum-well (MQW) 2D photonic crystal cavities (PhC) achieve low non-radiative recombination and high carrier confinement thus making them highly efficient emitters. In this study, we have investigated the lasing characteristics of high-beta(spontaneous emission coupling factor) buried MQW photonic crystal nanocavity lasers to clarify the theoretically-predicted thresholdless operation in high-beta nanolasers. The strong light and carrier confinement and low non-radiative recombination in our nanolasers have enabled us to clearly demonstrate very smooth lasing transition in terms of the light-in vs light-out curve and cavity linewidth. To clarify the thresholdless lasing behavior, we carried out a lifetime measurement and a photon correlation measurement, which also confirmed the predicted behavior. In addition, we systematically investigated the dependence of beta on the detuning frequency, which was in good agreement with a numerical simulation based on the finite difference time-domain method. This is the first convincing systematic study of nanolasers based on an MQW close to the thresholdless regime. PMID- 26907004 TI - Multi-spectral materials: hybridisation of optical plasmonic filters, a mid infrared metamaterial absorber and a terahertz metamaterial absorber. AB - Multi-spectral imaging systems typically require the cumbersome integration of disparate filtering materials and detectors in order to operate simultaneously in multiple spectral regions. Each distinct waveband must be detected at different spatial locations on a single chip or by separate chips optimised for each band. Here, we report on a single component that optically multiplexes visible, Mid Infrared (4.5 MUm) and Terahertz (126 MUm) radiation thereby maximising the spectral information density. We hybridise plasmonic and metamaterial structures to form a device capable of simultaneously filtering 15 visible wavelengths and absorbing Mid Infrared and Terahertz. Our synthetic multi-spectral component could be integrated with silicon complementary metal-oxide semiconductor technology where Si photodiodes are available to detect the visible radiation and micro-bolometers available to detect the Infrared/Terahertz and render an inexpensive, mass-producible camera capable of forming coaxial visible, Infrared and Terahertz images. PMID- 26907005 TI - Superradiance of a subwavelength array of classical nonlinear emitters. AB - We suggest a mechanism by which a superradiant burst emerges from a subwavelength array of nonlinear classical emitters that are not initially synchronized. The emitters interact via the field of their common radiative response. We show that only if the distribution of initial phases is not uniform does a non-zero field of radiative response arise, leading to a superradiant burst. Although this field cannot synchronize the emitters, it engenders long period envelopes for their fast oscillations. Constructive interference in the envelopes of several emitters creates a large fluctuation in dipole moments that results in a superradiant pulse. The intensity of this pulse is proportional to the square of the number of emitters participating in the fluctuation. PMID- 26907006 TI - Wide-angle structured light with a scanning MEMS mirror in liquid. AB - Microelectromechanical (MEMS) mirrors have extended vision capabilities onto small, low-power platforms. However, the field-of-view (FOV) of these MEMS mirrors is usually less than 90 degrees and any increase in the MEMS mirror scanning angle has design and fabrication trade-offs in terms of power, size, speed and stability. Therefore, we need techniques to increase the scanning range while still maintaining a small form factor. In this paper we exploit our recent breakthrough that has enabled the immersion of MEMS mirrors in liquid. While allowing the MEMS to move, the liquid additionally provides a "Snell's window" effect and enables an enlarged FOV (~ 150 degrees ). We present an optimized MEMS mirror design and use it to demonstrate applications in extreme wide-angle structured light. PMID- 26907007 TI - Theory and modeling of photodarkening-induced quasi static degradation in fiber amplifiers. AB - A theory of photodarkening-induced quasi-static degradation in fiber amplifiers is presented. As the doped core of a fiber photodarkens and continues to absorb more power converting it to heat, the intensity grating created by higher order mode interference with the fundamental mode moves toward the input end. This creates a persistent absorption grating that remains phase-shifted from the modal interference pattern. This leads to power transfer from the fundamental mode to a higher order mode with a very small frequency offset that occurs on a time scale of minutes to hours. This process is modeled in large mode area step index and photonic crystal fibers and is found to produce reasonable threshold values. PMID- 26907008 TI - Power scaling of ultrafast laser inscribed waveguide lasers in chromium and iron doped zinc selenide. AB - We report demonstration of Watt level waveguide lasers fabricated using Ultrafast Laser Inscription (ULI). The waveguides were fabricated in bulk chromium and iron doped zinc selenide crystals with a chirped pulse Yb fiber laser. The depressed cladding structure in Fe:ZnSe produced output powers of 1 W with a threshold of 50 mW and a slope efficiency of 58%, while a similar structure produced 5.1 W of output in Cr:ZnSe with a laser threshold of 350 mW and a slope efficiency of 41%. These results represent the current state-of-the-art for ULI waveguides in zinc based chalcogenides. PMID- 26907009 TI - Impact of nonzero boresight pointing error on ergodic capacity of MIMO FSO communication systems. AB - A thorough investigation of the impact of nonzero boresight pointing errors on the ergodic capacity of multiple-input/multiple-output (MIMO) free-space optical (FSO) systems with equal gain combining (EGC) reception under different turbulence models, which are modeled as statistically independent, but not necessarily identically distributed (i.n.i.d.) is addressed in this paper. Novel closed-form asymptotic expressions at high signal-to-noise ratio (SNR) for the ergodic capacity of MIMO FSO systems are derived when different geometric arrangements of the receive apertures at the receiver are considered in order to reduce the effect of nonzero inherent boresight displacement, which is inevitably present when more than one receive aperture is considered. As a result, the asymptotic ergodic capacity of MIMO FSO systems is evaluated over log-normal (LN), gamma-gamma (GG) and exponentiated Weibull (EW) atmospheric turbulence in order to study different turbulence conditions, different sizes of receive apertures as well as different aperture averaging conditions. It is concluded that the use of single-input/multiple-output (SIMO) and MIMO techniques can significantly increase the ergodic capacity respect to the direct path link when the inherent boresight displacement takes small values, i.e. when the spacing among receive apertures is not too big. The effect of nonzero additional boresight errors, which is due to the thermal expansion of the building, is evaluated in multiple-input/single-output (MISO) and single-input/single-output (SISO) FSO systems. Simulation results are further included to confirm the analytical results. PMID- 26907010 TI - Superconducting nanowire single photon detector at 532 nm and demonstration in satellite laser ranging. AB - Superconducting nanowire single-photon detectors (SNSPDs) at a wavelength of 532 nm were designed and fabricated aiming to satellite laser ranging (SLR) applications. The NbN SNSPDs were fabricated on one-dimensional photonic crystals with a sensitive-area diameter of 42 MUm. The devices were coupled with multimode fiber (phi = 50 MUm) and exhibited a maximum system detection efficiency of 75% at an extremely low dark count rate of <0.1 Hz. An SLR experiment using an SNSPD at a wavelength of 532 nm was successfully demonstrated. The results showed a depth ranging with a precision of ~8.0 mm for the target satellite LARES, which is ~3,000 km away from the ground ranging station at the Sheshan Observatory. PMID- 26907011 TI - Broadband mode division multiplexer using all-fiber mode selective couplers. AB - We report an all-fiber mode division multiplexer formed with cascaded mode selective couplers with significantly broadened bandwidth potentially spanning S, C and L band. This was achieved by matching the effective refractive indices over a wide wavelength range for the few mode fiber and the single mode fiber used in the coupler. The multiplexer provides high coupling efficiency (>55% for the worst case) for the 4 spatial modes over the entire wavelength range of 1515-1590 nm. The all-fiber construction provides mechanical stability. Experimental results for the coupling efficiency and the mode extinction ratio for each spatial mode are presented along with the far field radiation patterns. PMID- 26907012 TI - Low-loss light coupling with graded-index core polymer optical waveguides via 45 degree mirrors. AB - We experimentally investigate the optical loss of graded-index (GI) core polymer optical waveguides with a 45-degree mirror on their one end fabricated using the photo-addressing method. In addition, we also theoretically analyze the loss of GI square-core waveguides with mirrors using a ray-trace simulation tool. Then, in the waveguide based optical link including the optical path conversions via 45 degree mirrors, we show that GI waveguides realize lower total optical loss than conventional step-index (SI) core waveguides. The lower loss in the GI waveguide link is attributed to the tight optical confinement at the core center even after reflection at the mirrors. PMID- 26907013 TI - Magnetic circular dichroism of non-local surface lattice resonances in magnetic nanoparticle arrays. AB - Subwavelength metallic particles support plasmon resonances that allow extreme confinement of light down to the nanoscale. Irradiation with left- and right hand circularly polarized light results in the excitation of circular plasmon modes with opposite helicity. The Lorenz force lifts the degeneracy of the two modes in magnetic nanoparticles. Consequently, the confinement and frequency of localized surface plasmon resonances can be tuned by an external magnetic field. In this paper, we experimentally demonstrate this effect for nickel nanoparticles using magnetic circular dichroism (MCD). Besides, we show that non-local surface lattice resonances in periodic arrays of the same nanoparticles significantly enhance the MCD signal. A numerical model based on the modified long wavelength approximation is used to reproduce the main features in the experimental spectra and provide design rules for large MCD effects in sensing applications. PMID- 26907014 TI - Modal wavefront reconstruction in radial shearing interferometry with general aperture shapes. AB - Wavefront reconstruction in radial shearing interferometry with general aperture shapes is challenging because the problem may be ill-conditioned. Here we propose a Gram-Schmidt orthogonalization method to cope with off-axis wavefront reconstruction with any aperture type. The proposed method constructs a set of orthogonal basis functions and computes the corresponding expansion coefficients, which are converted into another set of expansion coefficients to reproduce the original wavefront. The method can effectively alleviate the ill-conditioning of the problem, and is numerically stable compared with the classic least-squares method, especially for non-circular apertures and in the presence of noise. Computer simulation and experimental results are presented to demonstrate the performance of the algorithm. PMID- 26907015 TI - Waveguide design parameters impact on absorption in graphene coated silicon photonic integrated circuits. AB - In this paper, we propose a new way of estimating the absorption in graphene coated silicon wire waveguides based on a self-developed, modified 2D Finite Difference Method, and use it to obtain a detailed absorption dependency of the waveguide design. For the first time, we observe peaks in the TM mode absorption curves, as well as the reversals of the dominantly absorbed mode with waveguide design variation, both of which have not been predicted previously theoretically, but have been implied through experimental results. We also provide a qualitative explanation of our novel numerical results, and explain how these results can be utilized in optimization of various graphene based integrated devices like optical modulators, photodetectors and optical polarizers. PMID- 26907016 TI - Correcting for accidental correlations in saturated avalanche photodiodes. AB - In this paper we present a general method for estimating rates of accidental coincidence between a pair of single photon detectors operated within their saturation regimes. By folding the effects of recovery time of both detectors and the detection circuit into an "effective duty cycle" we are able to accomodate complex recovery behaviour at high event rates. As an example, we provide a detailed high-level model for the behaviour of passively quenched avalanche photodiodes, and demonstrate effective background subtraction at rates commonly associated with detector saturation. We show that by post-processing using the updated model, we observe an improvement in polarization correlation visibility from 88.7% to 96.9% in our experimental dataset. This technique will be useful in improving the signal-to-noise ratio in applications which depend on coincidence measurements, especially in situations where rapid changes in flux may cause detector saturation. PMID- 26907017 TI - Watt-level narrow-linewidth Nd:YAG laser operating on 4F3/2->4I15/2 transition at 1834 nm. AB - We report on a 808 nm diode-pumped Nd:YAG narrow linewidth laser at 1834.25 nm using a compact two-mirror linear cavity. In free-running mode, a maximum output power of 1.10 W is obtained with a slope efficiency of about 11.1% at a cooling temperature of the laser crystal of 18 degrees C. Decreasing this temperature down to 8 degrees C increases the output power linearly up to 1.31 W. Shortening the laser cavity reduces the output power down to about 0.70 W but on a single longitudinal mode. These laser results represent the best laser performance ever achieved with any Nd-doped bulk material in the 1.8 um mid-infrared spectral range. PMID- 26907018 TI - Photosensitive cadmium telluride thin-film field-effect transistors. AB - We report on the graphene-seeded growth and fabrication of photosensitive Cadmium telluride (CdTe)/graphene hybrid field-effect transistors (FETs) subjected to a post-growth activation process. CdTe thin films were selectively grown on pre defined graphene, and their morphological, electrical and optoelectronic properties were systemically analyzed before and after the CdCl2 activation process. CdCl2-activated CdTe FETs showed p-type behavior with improved electrical features, including higher electrical conductivity (reduced sheet resistance from 1.09 * 10(9) to 5.55 * 10(7) Omega/sq.), higher mobility (from 0.025 to 0.20 cm2/(V.s)), and faster rise time (from 1.23 to 0.43 s). A post growth activation process is essential to fabricate high-performance photosensitive CdTe/graphene hybrid devices. PMID- 26907019 TI - Enhancing one dimensional sensitivity with plasmonic coupling: erratum. AB - Our manuscript contained data from unconverged rigorous coupled wave approximation (RCWA) simulations that resulted in incorrect description of minima locations. Here, converged RCWA simulations are presented with corrected minima behavior described. The principle of plasmonic enhancement and its use in ellipsometric test structures is maintained. PMID- 26907020 TI - Improved correction methods for field measurements of particulate light backscattering in turbid waters. AB - Monte Carlo simulations are used to compute the uncertainty associated to light backscattering measurements in turbid waters using the ECO-BB (WET Labs) and Hydroscat (HOBI Labs) scattering sensors. ECO-BB measurements provide an accurate estimate of the particulate volume scattering coefficient after correction for absorption along the short instrument pathlength. For Hydroscat measurements, because of a longer photon pathlength, both absorption and scattering effects must be corrected for. As the standard (sigma) correction potentially leads to large errors, an improved correction method is developed then validated using field inherent and apparent optical measurements carried out in turbid estuarine waters. Conclusions are also drawn to guide development of future short pathlength backscattering sensors for turbid waters. PMID- 26907021 TI - Integral imaging-based large-scale full-color 3-D display of holographic data by using a commercial LCD panel. AB - We propose a new type of integral imaging-based large-scale full-color three dimensional (3-D) display of holographic data based on direct ray-optical conversion of holographic data into elemental images (EIs). In the proposed system, a 3-D scene is modeled as a collection of depth-sliced object images (DOIs), and three-color hologram patterns for that scene are generated by interfering each color DOI with a reference beam, and summing them all based on Fresnel convolution integrals. From these hologram patterns, full-color DOIs are reconstructed, and converted into EIs using a ray mapping-based direct pickup process. These EIs are then optically reconstructed to be a full-color 3-D scene with perspectives on the depth-priority integral imaging (DPII)-based 3-D display system employing a large-scale LCD panel. Experiments with a test video confirm the feasibility of the proposed system in the practical application fields of large-scale holographic 3-D displays. PMID- 26907022 TI - Hybrid plasmonic lattices with tunable magneto-optical activity. AB - We report on the optical and magneto-optical response of hybrid plasmonic lattices that consist of pure nickel and gold nanoparticles in a checkerboard arrangement. Diffractive far-field coupling between the individual emitters of the lattices results in the excitation of two orthogonal surface lattice resonance modes. Local analyses of the radiation fields indicate that both the nickel and gold nanoparticles contribute to these collective resonances and, thereby, to the magneto-optical activity of the hybrid arrays. The strong effect of noble metal nanoparticles on the magneto-optical response of hybrid lattices opens up new avenues for the realization of sensitive and tunable magneto plasmonic nanostructures. PMID- 26907023 TI - Polarisation-selective hotspots in metallic ring stack arrays. AB - We demonstrate a simple, scalable fabrication method for producing large-area arrays of vertically stacked metallic micro-rings, embedded in a deformable polymer sheet. Unusual polarisation-dependent hotspots are found to dominate the reflection images. To understand their origin, the arrays are characterized using point-scanning optical spectroscopy and directly compared to numerical simulations. Individual ring stacks act as microlenses, while polarisation dependent hotspots arise at the connections between neighbouring stacks, which are comprised of parabolically-arranged parallel gold nanowires. The elastomeric properties of the polymer host opens the door to active control of the optics of this photonic material, through dynamic tuning of the nanowire spacings and array geometry. PMID- 26907024 TI - Enhancing scattering images for orientation recovery with diffusion map. AB - We explore the possibility for orientation recovery in single-molecule coherent diffractive imaging with diffusion map. This algorithm approximates the Laplace Beltrami operator, which we diagonalize with a metric that corresponds to the mapping of Euler angles onto scattering images. While suitable for images of objects with specific properties we show why this approach fails for realistic molecules. We introduce a modification of the form factor in the scattering images which facilitates the orientation recovery and should be suitable for all recovery algorithms based on the distance of individual images. PMID- 26907025 TI - Interferometric superlocalization of two incoherent optical point sources. AB - A novel interferometric method - SLIVER (Super Localization by Image inVERsion interferometry) - is proposed for estimating the separation of two incoherent point sources with a mean squared error that does not deteriorate as the sources are brought closer. The essential component of the interferometer is an image inversion device that inverts the field in the transverse plane about the optical axis, assumed to pass through the centroid of the sources. The performance of the device is analyzed using the Cramer-Rao bound applied to the statistics of spatially-unresolved photon counting using photon number-resolving and on-off detectors. The analysis is supported by Monte-Carlo simulations of the maximum likelihood estimator for the source separation, demonstrating the superlocalization effect for separations well below that set by the Rayleigh criterion. Simulations indicating the robustness of SLIVER to mismatch between the optical axis and the centroid are also presented. The results are valid for any imaging system with a circularly symmetric point-spread function. PMID- 26907026 TI - Pump-phase-noise-free optical wavelength data exchange between QAM signals with 50-GHz channel-spacing using coherent DFB pump. AB - An important challenge for implementing optical signal processing functions such as wavelength conversion or wavelength data exchange (WDE) is to avoid the introduction of linear and nonlinear phase noise in the subsystem. This is particularly important for phase noise sensitive, high-order quadrature-amplitude modulation (QAM) signals. In this paper, we propose and experimentally demonstrate an optical data exchange scheme through cascaded 2nd-order nonlinearities in periodically-poled lithium niobate (PPLN) waveguides using coherent pumping. The proposed coherent pumping scheme enables noise from the coherent pumps to be cancelled out in the swapped data after WDE, even with broad linewidth distributed feedback (DFB) pump lasers. Hence, this scheme allows phase noise tolerant processing functions, enabling the low-cost implementation of WDE for high-order QAM signals. We experimentally demonstrate WDEs between 10-Gbaud 4QAM (4QAM) signal and 12.5-Gbaud 4QAM (16QAM) signal with 3.5-MHz linewidth DFB pump lasers and 50-GHz channel spacing. Error-free operation is observed for the swapped QAM signals with coherent DFB pumping whilst use of free-running DFB pumps leads to visible error floors and unrecoverable phase errors. The phase noise cancellation in the coherent pump scheme is further confirmed by study of the recovered carrier phase of the converted signals. In addition to pump phase noise, the influence of crosstalk caused by the finite extinction ratio in WDE is also experimentally investigated for the swapped QAM signals. PMID- 26907027 TI - Temperature sensing up to 1300 degrees C using suspended-core microstructured optical fibers. AB - We demonstrate a new approach to high temperature sensing using femtosecond laser ablation gratings within silica suspended-core microstructured optical fibers. The simple geometry of the suspended-core fiber allows for femtosecond laser processing directly through the fiber cladding. Pure silica glass is used, allowing the sensor to be used up to temperatures as high as 1300 degrees C while still allowing the fibre to be spliced to conventional fiber. The sensor can also be wavelength division multiplexed, with three sensors in a single fiber demonstrated. PMID- 26907028 TI - Multi-port admittance model for quantifying the scattering response of loaded plasmonic nanorod antennas: erratum. AB - This erratum corrects the Acknowledgment in [Opt. Express23(4), 4459-4471 (2015)Opt. Express24(1), 365 (2016)]. PMID- 26907029 TI - Design of a thin disk amplifier with extraction during pumping for high peak and average power Ti:Sa systems (EDP-TD). AB - Combination of the scheme of extraction during pumping (EDP) and the Thin Disk (TD) technology is presented to overcome the limitations associated with thermal cooling of crystal and transverse amplified spontaneous emission in high average power laser systems based on Ti:Sa amplifiers. The optimized design of high repetition rate 1-10 PW Ti:Sapphire EDP-TD power amplifiers are discussed, including their thermal dynamic behavior. PMID- 26907030 TI - Flexible ultrathin-body single-photon avalanche diode sensors and CMOS integration. AB - We proposed the world's first flexible ultrathin-body single-photon avalanche diode (SPAD) as photon counting device providing a suitable solution to advanced implantable bio-compatible chronic medical monitoring, diagnostics and other applications. In this paper, we investigate the Geiger-mode performance of this flexible ultrathin-body SPAD comprehensively and we extend this work to the first flexible SPAD image sensor with in-pixel and off-pixel electronics integrated in CMOS. Experimental results show that dark count rate (DCR) by band-to-band tunneling can be reduced by optimizing multiplication doping. DCR by trap assisted avalanche, which is believed to be originated from the trench etching process, could be further reduced, resulting in a DCR density of tens to hundreds of Hertz per micrometer square at cryogenic temperature. The influence of the trench etching process onto DCR is also proved by comparison with planar ultrathin-body SPAD structures without trench. Photon detection probability (PDP) can be achieved by wider depletion and drift regions and by carefully optimizing body thickness. PDP in frontside- (FSI) and backside-illumination (BSI) are comparable, thus making this technology suitable for both modes of illumination. Afterpulsing and crosstalk are negligible at 2us dead time, while it has been proved, for the first time, that a CMOS SPAD pixel of this kind could work in a cryogenic environment. By appropriate choice of substrate, this technology is amenable to implantation for biocompatible photon-counting applications and wherever bended imaging sensors are essential. PMID- 26907031 TI - Investigation on slice direction dependent detectability of volumetric cone beam CT images. AB - We investigate the detection performance of transverse and longitudinal planes for various signal sizes (i.e., 1 mm to 8 mm diameter spheres) in cone beam computed tomography (CBCT) images. CBCT images are generated by computer simulation and images are reconstructed using an FDK algorithm. For each slice direction and signal size, a human observer study is conducted with a signal known-exactly/background-known-exactly (SKE/BKE) binary detection task. The detection performance of human observers is compared with that of a channelized Hotelling observer (CHO). The detection performance of an ideal linear observer is also calculated using a CHO with Laguerre-Gauss (LG) channels. The detectability of high contrast small signals (i.e., up to 4-mm-diameter spheres) is higher in the longitudinal plane than the transverse plane. It is also shown that CHO performance correlates well with human observer performance in both transverse and longitudinal plane images. PMID- 26907032 TI - Single-shot phase imaging with randomized light (SPIRaL). AB - We present a method for single-shot phase imaging with randomized light (SPIRaL). In SPIRaL, the complex (amplitude and phase) field of an object illuminated with a randomized coherent beam is captured with an image sensor, without the need for any reference light. The object field is retrieved from the single captured intensity image by a compressive sensing-based algorithm with a sparsity constraint. SPIRaL has higher observation speed, light efficiency, and flexibility of the implementation compared with previous methods. We demonstrate SPIRaL numerically and experimentally. PMID- 26907033 TI - Ultrafast acousto-optic imaging with ultrasonic plane waves. AB - Due to multiple light scattering inside biological tissues, deep non-invasive optical medical imaging is very challenging. Acousto-optic imaging is a technique coupling ultrasound and light that allows recovering optical contrast at depths of few centimeters with a millimeter resolution. Recent advances in acousto-optic imaging are using short focused ultrasound pulses often averaged over several hundred or thousand pulses. As the pulsing rate of commercial probes is limited to about few ultrasound cycles every 100 MUs, acquiring an acousto-optic image usually takes several tens of seconds due to the high number of acoustic pulses excitation. We propose here a new acousto-optic imaging technique based on the use of ultrasound plane waves instead of focused ones that allows increasing drastically the imaging rate. PMID- 26907034 TI - High-speed 3-D measurement with a large field of view based on direct-view confocal microscope with an electrically tunable lens. AB - We propose a new structure of confocal imaging system based on a direct-view confocal microscope (DVCM) with an electrically tunable lens (ETL). Since it has no mechanical moving parts to scan both the lateral (x-y) and axial (z) directions, the DVCM with an ETL allows for high-speed 3-dimensional (3-D) imaging. Axial response and signal intensity of the DVCM were analyzed theoretically according to the pinhole characteristics. The system was designed to have an isotropic spatial resolution of 20 um in both lateral and axial direction with a large field of view (FOV) of 10 * 10 mm. The FOV was maintained according to the various focal shifts as a result of an integrated design of an objective lens with the ETL. The developed system was calibrated to have linear focal shift over a range of 9 mm with an applied current to the ETL. The system performance of 3-D volume imaging was demonstrated using standard height specimens and a dental plaster. PMID- 26907035 TI - Wavelength bistability based on optical injection in a novel tunable dual mode laser. AB - A novel tunable dual mode laser is proposed based on a double-layer Bragg grating structure, named double-layer grating distributed Bragg reflector (DLG-DBR) laser. With controlling the gain saturation condition, different oscillating states can be observed. The nonlinear dynamics characteristics including bifurcation of the laser under optical injection with two different start-up sequences are analyzed with numerical simulations. Furthermore, we investigate the lasing wavelength bistability of the laser combined with its tuning characteristics theoretically. Optical memory operation based on the external optical injection locking bistability of the dual mode device is proposed. The memory operation can be achieved in the whole wavelength window with a 10 nm tuning range. A mode suppression ratio (MSR) of more than 45 dB is achieved between the two bistable states. PMID- 26907036 TI - Theoretical and experimental studies for high-repetition-rate disordered crystal lasers with harmonic self-mode locking. AB - A harmonically self-mode-locked Nd:Sr3Y2/(BO3)4 disordered crystal laser with subpicosecond pulse duration is demonstrated. We exploit the damped harmonic oscillator model to numerically verify that the mode spacing of the laser cavity can be modified to be the harmonics of the free spectral range of the Fabry-Perot cavity when the optical length of the laser cavity is close to a commensurate ratio of the optical length of the Fabry-Perot cavity. In experiment, the Fabry Perot cavity can be formed by the pump facet of the disordered crystal and the front mirror. A 110 GHz single-pulse harmonically mode-locked pulse train with pulse duration of 857 fs is experimentally achieved under optical lengths of 27.19 and 4.08 mm for the laser cavity and Fabry-Perot cavity respectively, corresponding to a fractional number of 20/3. A maximum output power of 162 mW is obtained at an incident pump power of 3.1 W. PMID- 26907037 TI - Determination of the Goos-Hanchen shift in dielectric waveguides via photo emission electron microscopy in the visible spectrum. AB - Photoemission Electron Microscopy (PEEM) is a versatile tool that relies on the photoelectric effect to produce high-resolution images. Pulse lasers allow for multi-photon PEEM where multiple photons are required excite a single electron. This non-linear process can directly image the near field region of electromagnetic fields in materials. We use this ability here to analyze wave propagation in a linear dielectric waveguide with wavelengths of 410 nm and 780 nm. The propagation constant of the waveguide can be extracted from the interference pattern created by the coupled and incident light and shows distinct polarization dependence. The electromagnetic field interaction at the boundaries can then be deduced which is essential to understand power flow in wave guiding structures. These results match well with simulations using finite element techniques. PMID- 26907038 TI - Ultra-strong enhancement of electromagnetic fields in an L-shaped plasmonic nanocavity. AB - Enhancements up to four orders of magnitude for electric intensity and three orders of magnitude for magnetic intensity are realized in a novel 2D L-shaped nanocavity. This structure makes full use of the dimension confinement, cavity resonance and tip enhancement to increase the electromagnetic intensity. An impedance matching model is developed to design this cavity by regarding the cavity as a load impedance where electromagnetic fields are maximally enhanced when maximum electromagnetic energy is delivered to the load impedance. Our L shaped nanocavity promises a variety of useful functionalities in sensing, nonlinear spectroscopy and signal processing. PMID- 26907039 TI - Elliptically polarized modes for the unidirectional excitation of surface plasmon polaritons. AB - We propose a new method for the directional excitation of surface plasmon polaritons by a metal nanoparticle antenna, based on the elliptical polarization of the normal modes of the antenna when it is in close proximity to a metallic substrate. The proposed theoretical model allows for the full characterization of the modes, giving the dipole configuration, frequency and lifetime. As a proof of principle, we have performed calculations for a dimer antenna and we report that surface plasmon polaritons can be excited in a given direction with an intensity of more than two orders of magnitude larger than in the opposite direction. Furthermore, using the fact that the response to any excitation can be written as a superposition of the normal modes, we show that this directionality can easily be accessed by exciting the system with a local source or a plane wave. Lastly, exploiting the interference between the normal modes, the directionality can be switched for a specific excitation. We envision the proposed mechanism to be a very useful tool for the design of antennas in layered media. PMID- 26907040 TI - Electrical excitation of waveguided surface plasmons by a light-emitting tunneling optical gap antenna. AB - We introduce a new type of electroplasmonic interfacing component to electrically generate surface plasmons. Specifically, an electron-fed optical tunneling gap antenna is integrated on a plasmonic waveguiding platform. When electrical charges are injected in the tunneling barrier of the gap antenna, a broad-band radiation is emitted from the feed area by a process identified as a thermal emission of hot electrons. Part of the emitted photons couples to surface plasmon modes sustained by the waveguide geometry. The transducing optical antenna is thus acting as a localized electrical source of surface plasmon polaritons. The integration of electrically-activated optical antennas into a plasmonic architecture mitigates the need for complex coupling scheme and proposes a solution for realizing nanoscale units at the interface between nano-electronics and photonics. PMID- 26907041 TI - Probing low-density carriers in a single atomic layer using terahertz parallel plate waveguides. AB - As novel classes of two-dimensional (2D) materials and heterostructures continue to emerge at an increasing pace, methods are being sought for elucidating their electronic properties rapidly, non-destructively, and sensitively. Terahertz (THz) time-domain spectroscopy is a well-established method for characterizing charge carriers in a contactless fashion, but its sensitivity is limited, making it a challenge to study atomically thin materials, which often have low conductivities. Here, we employ THz parallel-plate waveguides to study monolayer graphene with low carrier densities. We demonstrate that a carrier density of ~2 * 10(11) cm(-2), which induces less than 1% absorption in conventional THz transmission spectroscopy, exhibits ~30% absorption in our waveguide geometry. The amount of absorption exponentially increases with both the sheet conductivity and the waveguide length. Therefore, the minimum detectable conductivity of this method sensitively increases by simply increasing the length of the waveguide along which the THz wave propagates. In turn, enabling the detection of low conductivity carriers in a straightforward, macroscopic configuration that is compatible with any standard time-domain THz spectroscopy setup. These results are promising for further studies of charge carriers in a diverse range of emerging 2D materials. PMID- 26907042 TI - High resolution monitoring of strain fields in concrete during hydraulic fracturing processes. AB - We present a distributed fiber optic sensing scheme to image 3D strain fields inside concrete blocks during laboratory-scale hydraulic fracturing. Strain fields were measured by optical fibers embedded during casting of the concrete blocks. The axial strain profile along the optical fiber was interrogated by the in-fiber Rayleigh backscattering with 1-cm spatial resolution using optical frequency domain reflectometry (OFDR). The 3D strain fields inside the cubes under various driving pressures and pumping schedules were measured and used to characterize the location, shape, and growth rate of the hydraulic fractures. The fiber optic sensor detection method presented in this paper provides scientists and engineers an unique laboratory tool to understand the hydraulic fracturing processes via internal, 3D strain measurements with the potential to ascertain mechanisms related to crack growth and its associated damage of the surrounding material as well as poromechanically-coupled mechanisms driven by fluid diffusion from the crack into the permeable matrix of concrete specimens. PMID- 26907043 TI - Electrothermal MEMS fiber scanner for optical endomicroscopy. AB - We report a novel MEMS fiber scanner with an electrothermal silicon microactuator and a directly mounted optical fiber. The microactuator comprises double hot arm and cold arm structures with a linking bridge and an optical fiber is aligned along a silicon fiber groove. The unique feature induces separation of resonant scanning frequencies of a single optical fiber in lateral and vertical directions, which realizes Lissajous scanning during the resonant motion. The footprint dimension of microactuator is 1.28 x 7 x 0.44 mm3. The resonant scanning frequencies of a 20 mm long optical fiber are 239.4 Hz and 218.4 Hz in lateral and vertical directions, respectively. The full scanned area indicates 451 MUm x 558 MUm under a 16 Vpp pulse train. This novel laser scanner can provide many opportunities for laser scanning endomicroscopic applications. PMID- 26907044 TI - Gamma-ray radiation response at 1550 nm of fluorine-doped radiation hard single mode optical fiber. AB - We have investigated gamma-ray radiation response at 1550 nm of fluorine-doped radiation hard single-mode optical fiber. Radiation-induced attenuation (RIA) of the optical fiber was measured under intermittent gamma-ray irradiations with dose rate of ~10 kGy/h. No radiation hardening effect on the RIA by the gamma-ray pre-dose was found when the exposed fiber was bleached for long periods of time (27~47 days) at room-temperature. Photo-bleaching scheme upon 980 nm LD pumping has proven to be an effective deterrent to the RIA, particularly by suppressing the incipient RIA due to room-temperature unstable self-trapped hole defects (STHs). Large temperature dependence of the RIA of the optical fiber together with the photo-bleaching effect are worthy of note for reinforcing its radiation hard characteristics. PMID- 26907045 TI - Strong coupling of surface plasmon polaritons and ensembles of dye molecules. AB - We demonstrate the strong coupling of dye molecules to surface plasmon polaritons (SPPs) excited in the Kretschmann geometry and propagating at the interface of silver and dye-doped polymer. The dispersion curve of such a system, studied in the reflectometry experiments, is split into three branches and demonstrates an avoided crossing - the signature of a strong coupling. We have further studied the excitation spectra of the dye emission and found that the positions of the excitation peaks have a good match with the points in the dispersion curve determined by the reflectometry. At the same time, the analysis of the spectra of the plasmon-mediated spontaneous emission, decoupled to the prism and acquired at multiple collection angles, has resulted in a quite different dispersion curve exhibiting a non-trivial splitting into multiple branches. This suggests that the same plasmonic environment couples differently to absorbing and emitting dye molecules. PMID- 26907046 TI - Focus-tunable liquid lens with an aspherical membrane for improved central and peripheral resolutions at high diopters. AB - Liquid lens offers a simple solution to achieve tunable optical powers. This approach, however, suffers from deteriorated resolution at high diopters. In this study, a plano-convex liquid lens with aspherical cross-section is developed. Such configuration allows for the lens profiles at high diopters to be close to spherical shapes by alleviating the edge-clamping effects. Resolution tests of a 6mm lens with optimized asphericity exhibit improved resolutions in both center and peripheral regions at 40 and 100 diopters than the lenses with planar membranes. It shows that aspherical membranes can improve the resolving power of liquid lenses at high diopters, thus providing a new route of optimizing the imaging performance of adaptive liquid lenses for various applications. PMID- 26907047 TI - UV-free red electroluminescence from the cross-connected p-ZnO:Cu nanobushes/n GaN light emitting diode. AB - A p-ZnO:Cu/n-GaN heterojunction light emitting diode (LED) is fabricated by growing cross-connected p-ZnO:Cu nanobushes on n-GaN film using chemical vapor deposition under oxygen-rich condition. This LED emits stable UV-free red light of 677 nm and 745 nm. The electroluminescence (EL) light of this LED is tuned from ultraviolet (UV) of ZnO/GaN to UV-free red by the electronic interfacial transition from the conduction band of n-GaN to the deep acceptor levels of p ZnO:Cu. Both room temperature and low temperature (5K) photoluminescence spectra of ZnO:Cu indicate that the UV emission of ZnO is suppressed and the green emission is enhanced, which implies the formation of Cu-related deep levels introduced by intentionally doping Cu in ZnO. These deep levels help the EL red emission in the LED device. PMID- 26907048 TI - Comparisons of spectrally-enhanced asymmetrically-clipped optical OFDM systems. AB - Asymmetrically clipped optical orthogonal frequency-division multiplexing (ACO OFDM) is a technique that sacrifices spectral efficiency in order to transmit an orthogonally frequency-division multiplexed signal over a unipolar channel, such as a directly modulated direct-detection fiber or free-space channel. Several methods have been proposed to regain this spectral efficiency, including: asymmetrically clipped DC-biased optical OFDM (ADO-OFDM), enhanced U-OFDM (EU OFDM), spectral and energy efficient OFDM (SEE-OFDM), Hybrid-ACO-OFDM and Layered ACO-OFDM. This paper presents simulations up to high-order constellation sizes to show that Layered-ACO-OFDM offers the highest receiver sensitivity for a given optical power at spectral efficiencies above 3 bit/s/Hz. For comparison purposes, white Gaussian noise is added at the receiver, component nonlinearities are not considered, and the fiber is considered to be linear and dispersion-less. The simulations show that LACO-OFDM has a 7-dB sensitivity advantage over DC-biased OFDM (DCO-OFDM) for 1024-QAM at 87.5% of DCO-OFDM's spectral efficiency, at the same bit rate and optical power. This is approximately equivalent to a 4.4-dB advantage at the same spectral efficiency of 87.7% if 896-QAM were to be used for DCO-OFDM. PMID- 26907049 TI - 1 lambda * 1.44 Tb/s free-space IM-DD transmission employing OAM multiplexing and PDM. AB - We report the experimental demonstration of single wavelength terabit free-space intensity modulation direct detection (IM-DD) system employing both orbital angular momentum (OAM) multiplexing and polarization division multiplexing (PDM). In our experiment, 12 OAM modes with two orthogonal polarization states are used to generate 24 channels for transmission. Each channel carries 30 Gbaud Nyquist PAM-4 signal. Therefore an aggregate gross capacity record of 1.44 Tb/s (12 * 2 * 30 * 2 Gb/s) is acheived with a modulation efficiency of 48 bits/symbol. After 0.8m free-space transmission, the bit error rates (BERs) of all the channels are below the 20% hard-decision forward error correction (HD-FEC) threshold of 1.5 * 10(-2). After applying the decision directed recursive least square (DD-RLS) based filter and post filter, the BERs of two polarizations can be reduced from 5.3 * 10(-3) and 7.3 * 10(-3) to 2.2 * 10(-3) and 3.4 * 10(-3), respectively. PMID- 26907050 TI - Femtosecond-laser-inscribed sampled fiber Bragg grating with ultrahigh thermal stability. AB - We have successfully fabricated a series of sampled fiber Bragg gratings with easily adjustable sampling periods and duty cycles using an 800 nm femtosecond laser point-by-point inscription. The thermal stability of the fabricated fiber gratings was investigated using isochronal annealing tests, which indicated that the fiber gratings are capable of maintaining high reflectivity at temperatures of up to 1000 degrees C for 8 h. This demonstrates the potential of the developed sampled fiber Bragg gratings for use in multi-wavelength fiber lasers and a variety of high temperature applications. PMID- 26907051 TI - All-optical PT-symmetric conversion of amplitude (phase) modulation to phase (amplitude) modulation. AB - We study electromagnetic field propagation through a planar three-waveguide coupler with linear gain or loss in a configuration that is the optical analog of a quantum PT-symmetric system. This model is experimentally feasible on at least four proven architectures: lossy waveguide couplers, pumped waveguides couplers, non-Hermitian electronics and coupled pumped whispering gallery mode resonators. We show that our device provides all-optical amplitude (phase) to phase (amplitude) conversion in the PT-symmetric regime at given propagation lenghts. The device has a pi amplitude to phase conversion range if an extra binary phase is allowed in the reference signal, and a phase to amplitude conversion range that depends linearly on the gain-to-coupling ratio of the system. Our scheme may prove valuable in implementing phase shift keying formats, which have longer unrepeated transmission distance than intensity modulation schemes. PMID- 26907052 TI - Determination of true optical absorption and scattering coefficient of wooden cell wall substance by time-of-flight near infrared spectroscopy. AB - The true absorption coefficient (MUa) and reduced scattering coefficient (MU's) of the cell wall substance in Douglas fir were determined using time-of-flight near infrared spectroscopy. Samples were saturated with hexane, toluene or quinolone to minimize the multiple reflections of light on the boundary between pore-cell wall substance in wood. MU's exhibited its minimum value when the wood was saturated with toluene because the refractive index of toluene is close to that of the wood cell wall substance. The optical parameters of the wood cell wall substance calculated were MUa = 0.030 mm(-1) and MU's= 18.4 mm(-1). Monte Carlo simulations using these values were in good agreement with the measured time-resolved transmittance profiles. PMID- 26907053 TI - Backward terahertz radiation from intense laser-solid interactions. AB - We report a systematic study on backward terahertz (THz) radiation generation from laser-solid interactions by changing a variety of laser/plasma parameters. We demonstrate a high-energy (with an energy flux density reaching 80 MUJ/sr), broadband (>10 THz) plasma-based radiation source. The radiation energy is mainly distributed either in the >10 THz or <3 THz regions. A radial surface current formed by the lateral transport of low-energy electrons (LEE) is believed to be responsible for the radiation in the high-THz region (>10 THz), while high-energy surface fast electrons (SFE) accelerated along the target surface mainly contribute to lower frequency (<3 THz) radiation. The unifying explanation could be applied to backward THz radiation generation from solid targets with presence of relative small preplasmas. PMID- 26907054 TI - 1.1 MW peak power in doubly QML composite Nd:YVO4/Nd:YVO4/Nd:YVO4/KTP sub nanosecond green laser with EO and Bi-GaAs. AB - By simultaneously employing electro-optic (EO) modulator and Bi-doped GaAs, dual loss-modulated Q-switched and mode-locked (QML) multi-segment composite Nd:YVO4/Nd:YVO4/Nd:YVO4/KTP sub-nanosecond green laser is demonstrated with low repetition rate and high peak power. When the incident pump power is up to 6.93 W, only one mode-locking pulse underneath a Q-switching envelope is generated with sub-nanosecond pulse duration at one kilohertz repetition rate. An average output power of 445 mW and a pulse duration of 399 ps are obtained with the incident pump power of 11.13 W, corresponding to a peak power of 1.115 MW which is the highest one in doubly QML sub-nanosecond green laser by now. The laser characteristics are better than those obtained with EO and GaAs. The experimental results indicate that Bi-GaAs is a promising saturable absorber for dual-loss modulated QML laser. PMID- 26907055 TI - Extending plasma channel of filamentation with a multi-focal-length beam. AB - We propose a novel scheme that lengthens the plasma channel in filamentation with a multi-focal-length beam. Instead of one focal length introduced by a conventional convex lens, the multi-focal-length beam modulated by a spatial light modulator (SLM) produces a filament in an extended range with limited but strictly manipulated laser energy. The results show that the scheme is capable of doubling the filament length compared to a single-lens scheme with a 2-mJ input pulse. The filament location and length can be simply tuned by altering the spatial amplitude and phase or employing higher energies. Furthermore, the extended filament length leads to the generation of a broadened continuum ranging from visible (VIS) to infrared (IR) domain. This versatile scheme offers an efficient tool for the development of a variety of applications involving ultrafast nonlinear optics. PMID- 26907056 TI - Squeezed light from a diamond-turned monolithic cavity. AB - For some crystalline materials, a regime can be found where continuous ductile cutting is feasible. Using precision diamond turning, such materials can be cut into complex optical components with high surface quality and form accuracy. In this work we use diamond-turning to machine a monolithic, square-shaped, doubly resonant LiNbO3 cavity with two flat and two convex facets. When additional mild polishing is implemented, the Q-factor of the resonator is found to be limited only by the material absorption loss. We show how our monolithic square resonator may be operated as an optical parametric oscillator that is evanescently coupled to free-space beams via birefringent prisms. The prism arrangement allows for independent and large tuning of the fundamental and second harmonic coupling rates. We measure 2.6 +/- 0.5 dB of vacuum squeezing at 1064 nm using our system. Potential improvements to obtain higher degrees of squeezing are discussed. PMID- 26907057 TI - Diffraction effects incorporated design of a parallax barrier for a high-density multi-view autostereoscopic 3D display. AB - We present optical characteristics of view image provided by a high-density multi view autostereoscopic 3D display (HD-MVA3D) with a parallax barrier (PB). Diffraction effects that become of great importance in such a display system that uses a PB, are considered in an one-dimensional model of the 3D display, in which the numerical simulation of light from display panel pixels through PB slits to viewing zone is performed. The simulation results are then compared to the corresponding experimental measurements with discussion. We demonstrate that, as a main parameter for view image quality evaluation, the Fresnel number can be used to determine the PB slit aperture for the best performance of the display system. It is revealed that a set of the display parameters, which gives the Fresnel number of ~ 0.7 offers maximized brightness of the view images while that corresponding to the Fresnel number of 0.4 ~ 0.5 offers minimized image crosstalk. The compromise between the brightness and crosstalk enables optimization of the relative magnitude of the brightness to the crosstalk and lead to the choice of display parameter set for the HD-MVA3D with a PB, which satisfies the condition where the Fresnel number lies between 0.4 and 0.7. PMID- 26907058 TI - All-optical OXC transition strategy from WDM optical network to elastic optical network. AB - Elastic optical network (EON) has been proposed recently as a spectrum-efficient optical layer to adapt to rapidly-increasing traffic demands instead of current deployed wavelength-division-multiplexing (WDM) optical network. In contrast with conventional WDM optical cross-connect (OXCs) based on wavelength selective switches (WSSs), the EON OXCs are based on spectrum selective switches (SSSs) which are much more expensive than WSSs, especially for large-scale switching architectures. So the transition cost from WDM OXCs to EON OXCs is a major obstacle to realizing EON. In this paper, we propose and experimentally demonstrate a transition OXC (TOXC) structure based on 2-stage cascading switching architectures, which make full use of available WSSs in current deployed WDM OXCs to reduce number and port count of required SSSs. Moreover, we propose a contention-aware spectrum allocation (CASA) scheme for EON built with the proposed TOXCs. We show by simulation that the TOXCs reduce the network capital expenditure transiting from WDM optical network to EON about 50%, with a minor traffic blocking performance degradation and about 10% accommodated traffic number detriment compared with all-SSS EON OXC architectures. PMID- 26907059 TI - Coherent radio-frequency detection for narrowband direct comb spectroscopy. AB - We demonstrate a scheme for coherent narrowband direct optical frequency comb spectroscopy. An extended cavity diode laser is injection locked to a single mode of an optical frequency comb, frequency shifted, and used as a local oscillator to optically down-mix the interrogating comb on a fast photodetector. The high spectral coherence of the injection lock generates a microwave frequency comb at the output of the photodiode with very narrow features, enabling spectral information to be further down-mixed to RF frequencies, allowing optical transmittance and phase to be obtained using electronics commonly found in the lab. We demonstrate two methods for achieving this step: a serial mode-by-mode approach and a parallel dual-comb approach, with the Cs D1 transition at 894 nm as a test case. PMID- 26907060 TI - Efficient nonlinear equalizer for intra-channel nonlinearity compensation for next generation agile and dynamically reconfigurable optical networks. AB - In this work, we propose and experimentally demonstrate a novel low-complexity technique for fiber nonlinearity compensation. We achieved a transmission distance of 2818 km for a 32-GBaud dual-polarization 16QAM signal. For efficient implantation, and to facilitate integration with conventional digital signal processing (DSP) approaches, we independently compensate fiber nonlinearities after linear impairment equalization. Therefore this algorithm can be easily implemented in currently deployed transmission systems after using linear DSP. The proposed equalizer operates at one sample per symbol and requires only one computation step. The structure of the algorithm is based on a first-order perturbation model with quantized perturbation coefficients. Also, it does not require any prior calculation or detailed knowledge of the transmission system. We identified common symmetries between perturbation coefficients to avoid duplicate and unnecessary operations. In addition, we use only a few adaptive filter coefficients by grouping multiple nonlinear terms and dedicating only one adaptive nonlinear filter coefficient to each group. Finally, the complexity of the proposed algorithm is lower than previously studied nonlinear equalizers by more than one order of magnitude. PMID- 26907061 TI - Broad-tunable terahertz source with over-mode waveguide driven by train of electron bunches. AB - A broad-tunable free electron terahertz radiation source is proposed. In this source, a train of electron bunches with tunable bunching frequency is produced by a photocathode based DC-gun under excitation of a train of tunable laser pulses. These electron bunches are then applied to excite an over-mode waveguide, in which diverse guided modes are coupled into radiation with frequency determined by the bunching frequency. By this means, the tunable radiation with frequency extending from 0.1 THz to 1.2 THz can be obtained from one single structure model. In addition, compared with other sources, the proposed source is compact and easily achievable. PMID- 26907062 TI - 2D IR spectroscopy at 100 kHz utilizing a Mid-IR OPCPA laser source. AB - We present a 100 kHz 2D IR spectrometer. The system utilizes a ytterbium all normal dispersion fiber oscillator as a common source for the pump and seed beams of a MgO:PPLN OPCPA. The 1030 nm OPCPA pump is generated by amplification of the oscillator in cryocooled Yb:YAG amplifiers, while the 1.68 MUm seed is generated in a OPO pumped by the oscillator. The OPCPA outputs are used in a ZGP DFG stage to generate 4.65 MUm pulses. A mid-IR pulse shaper delivers pulse pairs to a 2D IR spectrometer allowing for data collection at 100 kHz. PMID- 26907063 TI - Image formation properties and inverse imaging problem in aperture based scanning near field optical microscopy. AB - Aperture based scanning near field optical microscopes are important instruments to study light at the nanoscale and to understand the optical functionality of photonic nanostructures. In general, a detected image is affected by both the transverse electric and magnetic field components of light. The discrimination of the individual field components is challenging as these four field components are contained within two signals in the case of a polarization resolved measurement. Here, we develop a methodology to solve the inverse imaging problem and to retrieve the vectorial field components from polarization and phase resolved measurements. Our methodology relies on the discussion of the image formation process in aperture based scanning near field optical microscopes. On this basis, we are also able to explain how the relative contributions of the electric and magnetic field components within detected images depend on the chosen probe. We can therefore also describe the influence of geometrical and material parameters of individual probes within the image formation process. This allows probes to be designed that are primarily sensitive either to the electric or magnetic field components of light. PMID- 26907064 TI - Quartz-enhanced photoacoustic detection of ethylene using a 10.5 MUm quantum cascade laser. AB - A quartz-enhanced photoacoustic spectroscopy (QEPAS) sensor has been developed for the sensitive detection of ethylene (C2H4) at 10.5 um using a continuous-wave distributed-feedback quantum cascade laser. At this long-wavelength infrared, the key acoustic elements of quartz tuning fork and micro-resonators were optimized to improve the detection signal-to-noise ratio by a factor of >4. The sensor calibration demonstrated an excellent linear response (R2>0.999) to C2H4 concentration at the selected operating pressure of 500 and 760 Torr. With a minimum detection limit of 50 parts per billion (ppb) achieved at an averaging time of 70 s, the sensor has been deployed for measuring the C2H4 efflux during the respiration of biological samples in an agronomic environment. PMID- 26907065 TI - Single-event transient imaging with an ultra-high-speed temporally compressive multi-aperture CMOS image sensor. AB - In the work described in this paper, an image reproduction scheme with an ultra high-speed temporally compressive multi-aperture CMOS image sensor was demonstrated. The sensor captures an object by compressing a sequence of images with focal-plane temporally random-coded shutters, followed by reconstruction of time-resolved images. Because signals are modulated pixel-by-pixel during capturing, the maximum frame rate is defined only by the charge transfer speed and can thus be higher than those of conventional ultra-high-speed cameras. The frame rate and optical efficiency of the multi-aperture scheme are discussed. To demonstrate the proposed imaging method, a 5*3 multi-aperture image sensor was fabricated. The average rising and falling times of the shutters were 1.53 ns and 1.69 ns, respectively. The maximum skew among the shutters was 3 ns. The sensor observed plasma emission by compressing it to 15 frames, and a series of 32 images at 200 Mfps was reconstructed. In the experiment, by correcting disparities and considering temporal pixel responses, artifacts in the reconstructed images were reduced. An improvement in PSNR from 25.8 dB to 30.8 dB was confirmed in simulations. PMID- 26907066 TI - Generation of arbitrary vector fields based on a pair of orthogonal elliptically polarized base vectors. AB - We present an arbitrary vector field with hybrid polarization based on the combination of a pair of orthogonal elliptically polarized base vectors on the Poincare sphere. It is shown that the created vector field is only dependent on the latitude angle 2chi but is independent on the longitude angle 2psi on the Poincare sphere. By adjusting the latitude angle 2chi, which is related to two identical waveplates in a common path interferometric arrangement, one could obtain arbitrary type of vector fields. Experimentally, we demonstrate the generation of such kind of vector fields and confirm the distribution of state of polarization by the measurement of Stokes parameters. Besides, we investigate the tight focusing properties of these vector fields. It is found that the additional degree of freedom 2chi provided by arbitrary vector field with hybrid polarization allows one to control the spatial structure of polarization and to engineer the focusing field. PMID- 26907067 TI - 1.89 kW all-fiberized and polarization-maintained amplifiers with narrow linewidth and near-diffraction-limited beam quality. AB - In this manuscript, we demonstrate high power, all-fiberized and polarization maintained amplifiers with narrow linewidth and near-diffraction-limited beam quality by simultaneously suppressing detrimental stimulated Brillouin scattering (SBS) and mode instability (MI) effects. Compared with strictly single frequency amplification, the SBS threshold is scaled up to 12 dB, 15.4 dB, and higher than 18 dB by subsequently using three-stage cascaded phase modulation systems. Output powers of 477 W, 1040 W, and 1890 W are achieved with full widths at half maximums (FWHMs) of within 6 GHz, ~18.5 GHz, and ~45 GHz, respectively. The MI threshold is increased from ~738 W to 1890 W by coiling the active fiber in the main amplifier. Both the polarization extinction ratio (PER) and beam quality (M2 factor) are maintained well during the power scaling process. To the best of our knowledge, this is the first demonstration of all-fiberized amplifiers with narrow linewidth, near linear polarization, and near-diffraction-limited beam quality at 2 kW power-level. PMID- 26907068 TI - Helicity sensitive enhancement of strong-field ionization in circularly polarized laser fields. AB - We investigate the strong-field ionization from p+/- orbitals driven by circularly polarized laser fields by solving the two-dimensional time-dependent Schrodinger equation in polar coordinates with the Lagrange mesh technique. Enhancement of ionization is found in the deep multiphoton ionization regime when the helicity of the laser field is opposite to that of the p electron, while this enhancement is suppressed when the helicities are the same. It is found that the enhancement of ionization is attributed to the multiphoton resonant excitation. The helicity sensitivity of the resonant enhancement is related to the different excitation-ionization channels in left and right circularly polarized laser fields. PMID- 26907069 TI - Numerical simulation of astigmatic liquid lenses tuned by a stripe electrode. AB - We propose a new design for tuning the astigmatism of liquid micro-lenses using electric field and hydrostatic pressure as control parameters. We explore the feasibility and operating range of the lens with a self-consistent numerical calculation of the electric field distribution and the shape of the two-phase interface. Equilibrium shapes, including surface profiles parallel and perpendicular to a stripe electrode, are extracted to determine the astigmatism. The wavefronts are decomposed into Zernike polynomials under zero defocus conditions using a commercial ray-tracing software. We observe that the global curvature of the lens is primarily controlled by the hydrostatic pressure, while asphericity and astigmatism are controlled by the electric field. For optimized electrode geometries and simultaneous control of pressure and electric fields the astigmatism can be tuned from Z6 = 0...0.38 MUm with minor changes in the focal length. PMID- 26907070 TI - Single shot fringe pattern phase demodulation using Hilbert-Huang transform aided by the principal component analysis. AB - Hybrid single shot algorithm for accurate phase demodulation of complex fringe patterns is proposed. It employs empirical mode decomposition based adaptive fringe pattern enhancement (i.e., denoising, background removal and amplitude normalization) and subsequent boosted phase demodulation using 2D Hilbert spiral transform aided by the Principal Component Analysis method for novel, correct and accurate local fringe direction map calculation. Robustness to fringe pattern significant noise, uneven background and amplitude modulation as well as local fringe period and shape variations is corroborated by numerical simulations and experiments. Proposed automatic, adaptive, fast and comprehensive fringe analysis solution compares favorably with other previously reported techniques. PMID- 26907071 TI - Emergence of resonant mode-locking via delayed feedback in quantum dot semiconductor lasers. AB - With conventional semiconductor lasers undergoing external optical feedback, a chaotic output is typically observed even for moderate levels of the feedback strength. In this paper we examine single mode quantum dot lasers under strong optical feedback conditions and show that an entirely new dynamical regime is found consisting of spontaneous mode-locking via a resonance between the relaxation oscillation frequency and the external cavity repetition rate. Experimental observations are supported by detailed numerical simulations of rate equations appropriate for this laser type. The phenomenon constitutes an entirely new mode-locking mechanism in semiconductor lasers. PMID- 26907072 TI - Detailed subsurface damage measurement and efficient damage-free fabrication of fused silica optics assisted by ion beam sputtering. AB - Formation of subsurface damage has an inseparable relationship with microscopic material behaviors. In this work, our research results indicate that the formation process of subsurface damage often accompanies with the local densification effect of fused silica material, which seriously influences microscopic material properties. Interestingly, we find ion beam sputtering (IBS) is very sensitive to the local densification, and this microscopic phenomenon makes IBS as a promising technique for the detection of nanoscale subsurface damages. Additionally, to control the densification effect and subsurface damage during the fabrication of high-performance optical components, a combined polishing technology integrating chemical-mechanical polishing (CMP) and ion beam figuring (IBF) is proposed. With this combined technology, fused silica without subsurface damage is obtained through the final experimental investigation, which demonstrates the feasibility of our proposed method. PMID- 26907073 TI - Polarization-insensitive PAM-4-carrying free-space orbital angular momentum (OAM) communications. AB - We present a simple configuration incorporating single polarization-sensitive phase-only liquid crystal spatial light modulator (SLM) to facilitate polarization-insensitive free-space optical communications employing orbital angular momentum (OAM) modes. We experimentally demonstrate several polarization insensitive optical communication subsystems by propagating a single OAM mode, multicasting 4 and 10 OAM modes, and multiplexing 8 OAM modes, respectively. Free space polarization-insensitive optical communication links using OAM modes that carry four-level pulse-amplitude modulation (PAM-4) signal are demonstrated in the experiment. The observed optical signal-to-noise ratio (OSNR) penalties are less than 1 dB in both polarization-insensitive N-fold OAM modes multicasting and multiple OAM modes multiplexing at a bit-error rate (BER) of 2e-3 (enhanced forward-error correction (EFEC) threshold). PMID- 26907074 TI - Ultra-compact III-V-on-Si photonic crystal memory for flip-flop operation at 5 Gb/s. AB - We report on a photonic crystal (PhC) nanolaser based on the heterogeneous integration of a III-V PhC nanocavity on SOI, configured to operate as a Set Reset Flip-Flop (SR-FF). The active layer is a nanobeam cavity made of a 650 nm * 285 nm InP-based wire waveguide evanescently coupled to 500 nm * 220 nm SOI wire waveguides, demonstrating a record-low footprint of only 6.2 MUm2. Injection locking enables optical bistability allowing for memory operation with only 6.4 fJ/bit switching energies and <50 ps response times. Bit-level SR-FF memory operation was evaluated at 5 Gb/s with PRBS-resembling data patterns, revealing error free operation with a negative power penalty. PMID- 26907075 TI - Measuring the second order correlation function and the coherence time using random phase modulation. AB - A new approach to measure the second order correlation function g(2) and the coherence time was investigated. The g(2) was calculated from the photon pair time interval distribution by direct numerical self-convolution with the high order correction. The accuracy of this method was examined using an optical fiber based Hanbury-Brown-Twiss interferometer with a pseudo-thermal light source. We found that the significance of the high order correction is related to the factor Itauc, which is the overlapping of the photon wave packets. A novel technique was also demonstrated to measure the coherence time tauc of a light source using the random phase modulation. This method is more suitable for a weak light source with a long coherence time using a simple experimental setup. PMID- 26907076 TI - Optical PT-symmetry and PT-antisymmetry in coherently driven atomic lattices. AB - We study an ensemble of ultracold atoms trapped in the one-dimensional optical lattices under the N level configuration to examine the absorption and dispersion properties modulated into different ways along the lattice direction z. We find these trapped atoms with a Gaussian density distribution in each period may exhibit either symmetry chip(z)=chip*(-z) or antisymmetry chip(z)=-chip*(-z) of parity-time (PT) in terms of the probe susceptibility. Such intriguing twofold modulations of real (chi'p) and imaginary (chi"p) susceptibilities with a pi/2 phase shift are attained by spatially modulating intensities or frequencies of one driving field in a suitable way. The PT-symmetric or PT-antisymmetric atomic lattices correspond in fact to complex photonic crystals and may be extended to develop functional devices like photonic diodes and transistors, a task impossible for real photonic crystals. PMID- 26907077 TI - Pixel pitch and particle energy influence on the dark current distribution of neutron irradiated CMOS image sensors. AB - The dark current produced by neutron irradiation in CMOS Image Sensors (CIS) is investigated. Several CIS with different photodiode types and pixel pitches are irradiated with various neutron energies and fluences to study the influence of each of these optical detector and irradiation parameters on the dark current distribution. An empirical model is tested on the experimental data and validated on all the irradiated optical imagers. This model is able to describe all the presented dark current distributions with no parameter variation for neutron energies of 14 MeV or higher, regardless of the optical detector and irradiation characteristics. For energies below 1 MeV, it is shown that a single parameter has to be adjusted because of the lower mean damage energy per nuclear interaction. This model and these conclusions can be transposed to any silicon based solid-state optical imagers such as CIS or Charged Coupled Devices (CCD). This work can also be used when designing an optical imager instrument, to anticipate the dark current increase or to choose a mitigation technique. PMID- 26907078 TI - Energy transfer induced improvement of luminescent efficiency and thermal stability in phosphate phosphor. AB - Ce3+ and Eu2+/Tb3+/Mn2+ ions codoped Ca6BaP4O17 (CBPO) phosphors have been prepared via a high-temperature solid state reaction. The structural refinement indicates that the as-prepared phosphors crystallize in monoclinic phase (C2/m) and there are two Ca sites and one Ba site in host lattice. The doping ions are determined to occupy Ca sites and the emission of Ce3+ and Eu2+ ions at different Ca sites were identified and discussed. Since bright blue and yellow emissions were observed from Ce3+and Eu2+ ions monodoped CBPO under n-UV excitation, respectively. They were codoped into the CBPO for designing energy transfer from Ce3+ to Eu2+ to improve the luminescence efficiency of Eu2+. In addition, Tb3+ ions were added into the CBPO:Ce3+ system for realizing highly efficient green emission. The energy transfer mechanisms from Ce3+ to Eu2+/Tb3+ ions were discussed. Interestingly, the incorporation of Mn2+ ions into the CBPO:Ce3+ system enhanced the blue emission of Ce3+ ions due to the modification of crystal lattice. Finally, the thermal stability of CBPO:Ce3+, Eu2+/Tb3+/Mn2+ phosphors were investigated systematically and corresponding mechanisms were proposed. Based on these results, the as-prepared CBPO:Ce3+, Eu2+/Tb3+/Mn2+ phosphors can act as potential blue, yellow, green, and emission-tunable phosphors for n-UV based white LEDs. PMID- 26907079 TI - Gauging low-dose X-ray phase-contrast imaging at a single and large propagation distance. AB - The interactions of a beam of hard and spatio-temporally coherent X-rays with a soft-matter sample primarily induce a transverse distribution of exit phase variations deltaphi (retardations or advancements in pieces of the wave front exiting the object compared to the incoming wave front) whose free-space propagation over a distance z gives rise to intensity contrast gz. For single distance image detection and |deltaphi| ? 1 all-order-in-z phase-intensity contrast transfer is linear in deltaphi. Here we show that ideal coherence implies a decay of the (shot-)noise-to-signal ratio in gz and of the associated phase noise as z(-1/2) and z(-1), respectively. Limits on X-ray dose thus favor large values of z. We discuss how a phase-scaling symmetry, exact in the limit deltaphi -> 0 and dynamically unbroken up to |deltaphi| ~ 1, suggests a filtering of gz in Fourier space, preserving non-iterative quasi-linear phase retrieval for phase variations up to order unity if induced by multi-scale objects inducing phase variations deltaphi of a broad spatial frequency spectrum. Such an approach continues to be applicable under an assumed phase-attenuation duality. Using synchrotron radiation, ex and in vivo microtomography on frog embryos exemplifies improved resolution compared to a conventional single-distance phase-retrieval algorithm. PMID- 26907080 TI - Regular oscillations and random motion of glass microspheres levitated by a single optical beam in air: publisher's note. AB - This publisher's note amends a recent publication [Opt. Express24(3), 2850-2857 (2016)] to include Acknowledgments. PMID- 26907081 TI - High sensitivity UV fluorescence spectroscopy based on an optofluidic jet waveguide: erratum. AB - This publisher's note corrects the author listing of a publication. PMID- 26907083 TI - Indirect treatment comparison of belatacept versus tacrolimus from a systematic review of immunosuppressive therapies for kidney transplant patients. AB - OBJECTIVE: End-stage renal disease is the final and irreversible stage in chronic kidney disease, leading to patient mortality, unless managed by dialysis or transplantation (the treatment of choice). This study aimed to compare a currently recommended immunosuppressive treatment, tacrolimus, against a newer treatment, belatacept, using indirect treatment comparison (ITC) techniques since no head-to-head randomized controlled trials (RCTs) comparing tacrolimus against belatacept currently exist. METHODS: ITC was employed to calculate estimates for the relative risks and mean difference of tacrolimus against belatacept. The choice of the Bucher ITC model was driven by the available data and the simple indirect treatment comparison involving three treatments was considered appropriate. RESULTS: The results of the indirect analysis showed no significant differences between belatacept and tacrolimus treatments for mortality and graft loss. The acute rejection rate was significantly lower with tacrolimus (Prograf* and Advagraf (*) ) compared with belatacept (0.22 [0.13, 0.39] to 0.44 [0.20, 0.99]). CONCLUSIONS: The results of this systematic review and meta-analysis suggests that tacrolimus is significantly superior to belatacept in terms of acute rejection outcomes but comparable for graft and patient survival. Further research should include a properly designed clinical trial comparing tacrolimus against belatacept directly. LIMITATIONS: These include variations in terms of clinical and design differences among the trials, weaknesses in the Bucher method and the lack of long-term clinical trial data with tacrolimus to compare with the recent long-term (7 years) belatacept trial data. PMID- 26907082 TI - On-Demand Targeting: Investigating Biology with Proximity-Directed Chemistry. AB - Proximity enhancement is a central chemical tenet underpinning an exciting suite of small-molecule toolsets that have allowed us to unravel many biological complexities. The leitmotif of this opus is "tethering"-a strategy in which a multifunctional small molecule serves as a template to bring proteins/biomolecules together. Scaffolding approaches have been powerfully applied to control diverse biological outcomes such as protein-protein association, protein stability, activity, and improve imaging capabilities. A new twist on this strategy has recently appeared, in which the small-molecule probe is engineered to unleash controlled amounts of reactive chemical signals within the microenvironment of a target protein. Modification of a specific target elicits a precisely timed and spatially controlled gain-of-function (or dominant loss-of-function) signaling response. Presented herein is a unique personal outlook conceptualizing the powerful proximity-enhanced chemical biology toolsets into two paradigms: "multifunctional scaffolding" versus "on-demand targeting". By addressing the latest advances and challenges in the established yet constantly evolving multifunctional scaffolding strategies as well as in the emerging on-demand precision targeting (and related) systems, this Perspective is aimed at choosing when it is best to employ each of the two strategies, with an emphasis toward further promoting novel applications and discoveries stemming from these innovative chemical biology platforms. PMID- 26907084 TI - The Relationship Between Plasma Whole Blood Viscosity and Cardiovascular Events in Patients With Chronic Kidney Disease. AB - BACKGROUND: Plasma levels of estimated whole blood viscosity (eWBV) have been increased by endothelial inflammation. Because there were no consistent data for assessing the eWBV levels for prediction of cardiovascular event (CVE) in patients with chronic kidney disease (CKD). We aimed to investigate the relationship between plasma eWBV levels and CVEs in patients with CKD. MATERIALS AND METHODS: We conducted a prospective, cross-sectional, long-term follow-up study, assessing the relationship between plasma eWBV levels and CVE (either fatal or nonfatal) in patients with newly diagnosed CKD. We also evaluated estimated glomerular filtration rate (eGFR), pentraxin 3 (PTX3), high-sensitivity C-reactive protein (hsCRP), and flow-mediated dilatation (FMD). RESULTS: Study patients were divided into 2 groups: patients with CVE and patients without CVE. The eWBV levels were higher in patients with CVE. Additionally, PTX3 and hsCRP were higher, and FMD and eGFR were lower in patients with CVE compared to those without CVE. According to the Cox regression analysis, WBV, plasma asymmetric dimethylarginine levels, FMD, hsCRP, eGFR, systolic blood pressure, calcium, and history of diabetes were independent predictors of CVEs in patients with CKD. Kaplan Meier survival curves were generated to establish the impact of the WBV on the cumulative survival of the cohort. Patients with eWBV values higher than 5.2 centipoise (cP) had lower survival rates when compared to patients with eWBV values lower than 5.2 cP (log rank = 4.49 df = 1 P = .034). CONCLUSION: In conclusion, plasma eWBV levels may increase the presence of lower eGFR and affect CVE in patients with CKD independent of classical and unconventional risk factors. PMID- 26907085 TI - Quality of Life in Children and Adolescents With Rare Bleeding Disorders in Southern Iran. AB - The aim of this study is to evaluate quality of life (QOL) in patients with rare bleeding disorders (RBDs). In this cross-sectional study, 52 consecutive children aged between 4 and 18 years old with RBDs registered at the Haemophila Center of Fars province in Southern Iran were investigated from January to April 2015. Quality of life was evaluated using Haemo-QOL questionnaire. Final score is defined between 0 and 100, and higher score of QOL shows worse condition. P value less than .05 was considered statistically significant. Mean age of the patients was 13.96 +/- 4.50 and ranged from 4 to 18 years old including 28 males and 24 females. Family and friends were the 2 most impaired domains of Haemo-QOL in these patients. In univariate analysis, bleeding severity based on bleeding score, health status, and being bothered by the disease showed statistically significant correlations with QOL of the patients ( P < .05). In multiple linear regression models, only degree of being bothered by the disease was determined as an independent influencing factor on QOL. Taking together, Haemo-QOL of children with RBDs was better than what was reported in patients with hemophilia in our region, but it was worse than that reported in patients with hemophilia in other developing and developed countries. Due to chronic feature of bleeding disorders, more attention to different aspects of the disease, especially in 2 dimensions of family and friends through considering educational and psychological program for the patients and their family, are recommended to improve QOL of the patients with RBDs. PMID- 26907086 TI - [Organophosphate pesticides and neuropsychological and motor effects in the Maule Region, Chile]. AB - OBJECTIVE: To evaluate organophosphate pesticide exposure and neuropsychological and motor performance in agricultural and non-agricultural workers in the Maule Region in Chile. METHOD: Analytic cross-sectional study in 93 exposed farm workers and 84 unexposed non-agricultural workers. A battery of four neuropsychological tests was administered together with a neuro-motor physical examination. RESULTS: On the Weschler adult intelligence scale (WAIS-IV), exposed agricultural workers exhibited poorer performance than non-agricultural workers in verbal comprehension (beta=-3.2; p=0.034) and processing speed (beta=-4.4; p=0.036) and in the full scale (beta=-4; p=0.016), as well as in discrimination sensitivity (beta=1, p=0,009), adjusted by years of schooling and/or age. CONCLUSIONS: We suggest the development of policies and regulations for the control, sale and use of organophosphate pesticides and intervention strategies on safety measures aimed at the exposed population. PMID- 26907087 TI - Creatine target engagement with brain bioenergetics: a dose-ranging phosphorus-31 magnetic resonance spectroscopy study of adolescent females with SSRI-resistant depression. AB - Major depressive disorder (MDD) often begins during adolescence and is projected to become the leading cause of global disease burden by the year 2030. Yet, approximately 40 % of depressed adolescents fail to respond to standard antidepressant treatment with a selective serotonin reuptake inhibitor (SSRI). Converging evidence suggests that depression is related to brain mitochondrial dysfunction. Our previous studies of MDD in adult and adolescent females suggest that augmentation of SSRI pharmacotherapy with creatine monohydrate (CM) may improve MDD outcomes. Neuroimaging with phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS) can measure the high-energy phosphorus metabolites in vivo that reflect mitochondrial function. These include phosphocreatine (PCr), a substrate for the creatine kinase reaction that produces adenosine triphosphate. As part of the National Institute of Mental Health's experimental medicine initiative, we conducted a placebo-controlled dose-ranging study of adjunctive CM for adolescent females with SSRI-resistant MDD. Participants were randomized to receive placebo or CM 2, 4 or 10 g daily for 8 weeks. Pre- and post-treatment (31)P-MRS scans were used to measure frontal lobe PCr, to assess CM's target engagement with cerebral energy metabolism. Mean frontal lobe PCr increased by 4.6, 4.1 and 9.1 % in the 2, 4 and 10 g groups, respectively; in the placebo group, PCr fell by 0.7 %. There was no group difference in adverse events, weight gain or serum creatinine. Regression analysis of PCr and depression scores across the entire sample showed that frontal lobe PCr was inversely correlated with depression scores (p = 0.02). These results suggest that CM achieves target engagement with brain bioenergetics and that the target is correlated with a clinical signal. Further study of CM as a treatment for adolescent females with SSRI-resistant MDD is warranted. PMID- 26907088 TI - Aspartate attenuates intestinal injury and inhibits TLR4 and NODs/NF-kappaB and p38 signaling in weaned pigs after LPS challenge. AB - PURPOSE: This study was conducted to investigate whether aspartate (Asp) could alleviate Escherichia coli lipopolysaccharide (LPS)-induced intestinal injury by modulating intestine inflammatory response. METHODS: Twenty-four weaned piglets were divided into four treatments: (1) non-challenged control; (2) LPS-challenged control; (3) LPS + 0.5 % Asp; and (4) LPS + 1.0 % Asp. After feeding with control, 0.5 or 1.0 % Asp-supplemented diets for 21 days, pigs were injected intraperitoneally with saline or LPS. At 4 h postinjection, blood and intestine samples were obtained. RESULTS: Asp supplementation to LPS-challenged pigs improved intestinal morphology, indicated by higher jejunal and ileal villus height/crypt depth ratio and lower ileal crypt depth linearly or quadratically. Asp also improved intestinal barrier function, indicated by increased jejunal and ileal diamine oxidase activities as well as enhanced protein expression of jejunal claudin-1 linearly or quadratically. In addition, Asp decreased plasma, jejunal and ileal tumor necrosis factor-alpha concentration and ileal caspase-3 protein expression linearly and quadratically. Moreover, Asp down-regulated the mRNA expression of toll-like receptor 4 (TLR4) and nucleotide-binding oligomerization domain protein (NOD) signaling-related genes, nuclear factor kappaB (NF-kappaB) p65 and p38, decreased phosphorylation of jejunal p38, and increased phosphorylation of ileal extracellular signal-related kinase 1/2 linearly or quadratically. Finally, Asp increased mRNA expressions of TLR4 and NOD signaling negative regulators including radioprotective 105, suppressor of cytokine signaling 1, toll-interacting protein, Erbb2 interacting protein and centaurin beta1 linearly or quadratically. CONCLUSIONS: These results indicate that Asp supplementation is associated with inhibition of TLR4 and NODs/NF-kappaB and p38 signaling pathways and concomitant improvement of intestinal integrity under an inflammatory condition. PMID- 26907089 TI - Oregano demonstrates distinct tumour-suppressive effects in the breast carcinoma model. AB - PURPOSE: There has been a considerable interest in the identification of natural plant foods for developing effective agents against cancer. Thus, the anti-tumour effects of oregano in the in vivo and in vitro breast cancer model were evaluated. METHODS: Lyophilized oregano (ORE) was administered at two concentrations of 0.3 and 3 % through diet. The experiment was terminated 14 weeks after carcinogen administration. At autopsy, mammary tumours were removed and prepared for histopathological and immunohistochemical analysis. Moreover, in vitro evaluation in MCF-7 cells was carried out. RESULTS: Low-dose ORE suppressed tumour frequency by 55.5 %, tumour incidence by 44 %, and tumour volume by 44.5 % compared to control animals. Analysis of rat tumour cells showed Ki67, VEGFR-2, CD24, and EpCAM expression decrease and caspase-3 expression increase after low dose ORE treatment. High-dose ORE lengthened tumour latency by 12.5 days; moreover, Bcl-2, VEGFR-2, CD24, and EpCAM expression decrease and caspase-3 expression increase in carcinoma cells were observed. Histopathological analysis revealed a decrease in the ratio of high-/low-grade carcinomas in both treated groups. In vitro studies showed that ORE decreased survival and proliferation of MCF-7 cells. In ORE-treated MCF-7 cells, an increase in cells expressing sub-G 0/G 1 DNA content and an increase in the percentage of annexin V/PI positive MCF 7 cells were observed. In vitro, both caspase-dependent and possible non-caspase dependent apoptotic pathways were found. The deactivation of anti-apoptotic activity of Bcl-2, a decrease in mitochondrial membrane potential, and the activation of mitochondrial apoptosis pathway were observed in the ORE-treated MCF-7 cells. CONCLUSIONS: Our results demonstrate, for the first time, a distinct tumour-suppressive effect of oregano in the breast cancer model. PMID- 26907091 TI - The impact of stress on fertility treatment. AB - PURPOSE OF REVIEW: The goal of this review was to summarize the recent research on the relationship between stress and assisted reproductive technology treatment. RECENT FINDINGS: Women and men with infertility report high levels of distress that can impact their quality of life. There are numerous psychosocial interventions, including cognitive behavior therapy and/or self-help ones, which may decrease distress, increase patient retention and improve pregnancy rates. SUMMARY: Patient distress is an important factor to consider. Decreasing burden of care may lead to significant improvements in assisted reproductive technology outcome. PMID- 26907090 TI - FUT2-dependent breast milk oligosaccharides and allergy at 2 and 5 years of age in infants with high hereditary allergy risk. AB - PURPOSE: Manifestation of allergic disease depends on genetic predisposition, diet and commensal microbiota. Genetic polymorphism of mothers determines their breast milk glycan composition. One major determinant is the fucosyltransferase 2 (FUT2, secretor gene) that was shown to be linked to commensal microbiota establishment. We studied whether FUT2-dependent breast milk oligosaccharides are associated with allergic disease in breast-fed infants later in life. METHODS: We analyzed FUT2-dependent oligosaccharides in breast milk samples of mothers (n = 266) from the placebo group of a randomized placebo-controlled trial of prebiotics and probiotics as preventive against allergic disease in infants with high allergy risk (trial registry number: NCT00298337). Using logistic regression models, we studied associations between FUT2-dependent breast milk oligosaccharides and incidence of allergic disease at 2 and 5 years of age. RESULTS: At 2 years, but not at 5 years of age, we observed a presumed lower incidence (p < 0.1) for IgE-associated eczema manifestation in C-section-born infants who were fed breast milk containing FUT2-dependent oligosaccharides. By logistic regression, we observed a similar relation (p < 0.1) between presence of FUT2-dependent breast milk oligosaccharides and IgE-associated disease and IgE associated eczema in C-section-born infants only. When testing with the levels of breast milk oligosaccharide 2'-fucosyllactose as proxy for FUT2 activity, we observed significant (p < 0.05) associations in the C-section-born infants with 'any allergic disease,' IgE-associated disease, eczema and IgE-associated eczema. CONCLUSION: The data indicate that infants born by C-section and having a high hereditary risk for allergies might have a lower risk to manifest IgE-associated eczema at 2 years, but not 5 years of age, when fed breast milk with FUT2 dependent milk oligosaccharides. Further studies with larger cohorts and especially randomized controlled intervention trials are required to build on these preliminary observations. PMID- 26907092 TI - Normative data for Adelta contact heat evoked potentials in adult population: a multicenter study. AB - There has been a significant increase over recent years in the use of contact heat evoked potentials (CHEPs) for the evaluation of small nerve fiber function. Measuring CHEP amplitude and latency has clinical utility for the diagnosis and assessment of conditions with neuropathic pain. This international multicenter study aimed to provide reference values for CHEPs to stimuli at 5 commonly examined body sites. Contact heat evoked potentials were recorded from 226 subjects (114 females), distributed per age decade between 20 and 79 years. Temperature stimuli were delivered by a thermode (32 degrees C-51 degrees C at a rate of 70 degrees C/s). In phase I of the study, we investigated side-to-side differences and reported the maximum normal side-to-side difference in Adelta CHEP peak latency and amplitude for leg, forearm, and face. In phase II, we obtained normative data for 3 CHEP parameters (N2P2 amplitude, N2 latency, and P2 latency), stratified for gender and age decades from face, upper and lower limbs, and overlying cervical and lumbar spine. In general, larger CHEP amplitudes were associated with higher evoked pain scores. Females had CHEPs of larger amplitude and shorter latency than males. This substantive data set of normative values will facilitate the clinical use of CHEPs as a rapid, noninvasive, and objective technique for the assessment of patients presenting with neuropathic pain. PMID- 26907094 TI - A benzoate-activated promoter from Aspergillus niger and regulation of its activity. AB - The filamentous fungus Aspergillus niger is able to use benzoic acid as a sole carbon source by conversion to protocatechuic acid and subsequent metabolism. Synthesis of the first enzyme in this metabolic pathway, benzoate p-hydroxylase, is encoded by the bphA gene and positively regulated at the transcriptional level by benzoic acid. Methyl benzoate and para-aminobenzoate also act as inducers of the bphA gene. We show that bphA expression in A. niger in response to benzoate is confined to a 530-bp fragment from the bphA promoter region from -787 to -509 bp from the transcriptional start site. Electrophoretic mobility-shift assays show that a benzoate-response element, consisting of a single 6-bp sequence (5' TAGTCA-3') within a 51-bp sequence in this region, is most likely to be involved in binding of one or more proteins that modulate the activity of the promoter in response to benzoic acid. We show through fusion of promoter fragments with the green fluorescent protein that the active sequences are located within a 200-bp sequence containing the TAGTCA benzoate-response element. Identification of the benzoate-response element in the bphA promoter region constitutes the first step in the development of a benzoate-inducible promoter system that could be used to control gene expression in fungi, and possibly in other organisms, such as plant and animal cells. PMID- 26907093 TI - Radiation recall dermatitis induced by sorafenib : A case study and review of the literature. AB - BACKGROUND: Radiation recall dermatitis (RRD) is an acute inflammatory reaction confined to previously irradiated skin, mainly subsequent to the administration of certain chemotherapeutics. Here we present a rare case of RRD induced by the oral multikinase inhibitor sorafenib. CASE REPORT: A 77-year-old male with hepatocellular carcinoma was irradiated at ten different sites for bone metastases with 20-36 Gray in 5-12 fractions from January to March 2015. Sorafenib 400 mg was administered twice daily from mid-March. One week later the patient presented with fever and erythematous lesions on the right upper arm, mandible, and trunk. All skin symptoms were confined to previously irradiated areas. After RRD was diagnosed by exclusion of other causes and skin biopsy, sorafenib was paused. With the administration of topical corticosteroids and oral antihistamines, the skin reaction subsided within several days. Sorafenib was readministered after 3 weeks, which did not lead to recurrence of RRD but did cause fluctuating fever. DISCUSSION: Only four other such cases have been reported in the literature and WHO pharmacovigilance database on individual case safety reports. The current report is the first to show a potential relationship between the severity of sorafenib-induced RRD and radiation dose, histopathological features, and simultaneous acute radiation dermatitis and mucositis. CONCLUSION: RRD induced by sorafenib is a rare phenomenon, but should be considered in patients showing erythematous skin lesions 1-2 weeks after initiation of the drug, predominantly in areas where skin has been irradiated with an equivalent dose >= 30 Gy. Discontinuation of sorafenib with possible readministration should be evaluated with respect to the clinical situation and severity of reaction. PMID- 26907095 TI - Proposed minimal panel of antibodies for cost-effectiveness and accuracy in acute leukemias immunophenotyping: Prospective study at a tertiary care center. AB - INTRODUCTION: Flowcytometry has an essential role in the diagnosis and classification of acute leukemias. However, there exists a great degree of inter laboratory variability on issues like panel selection, antibody combinations, gating strategies, fluorochromes, and clonal selection. AIM: The primary aim of this study was to derive a minimal panel of antibodies and evaluate its diagnostic usefulness in acute leukemias by flowcytometry by using the detailed immune-phenotype of different lineage-specific or non-specific markers. MATERIALS AND METHODS: This prospective observational study involved 400 newly diagnosed cases of acute leukemias. Bone marrow aspirate samples were subjected to morphological evaluation, cytogenetics and flow cytometric immunophenotyping. RESULTS: A minimal panel of eight antibodies comprising of CD45/CD34/CD19/MPO/cytoCD3/CD64/CD117/CD79a was derived by applying different permutations and combinations with a diagnostic yield of 97.5%. The minimal panel was further validated by testing in an independent cohort of patients with similar demographic characteristics, where it showed a high diagnostic yield of 98% in comparison with the screening panels proposed by other recently published studies. CONCLUSION: It may be concluded that the diagnostic performance of the eight antibody panel is better than most other panels used across the different laboratories in terms of yield, number of antibodies used and the scientific approach used to derive and validate the results and so henceforth may be applied in any setting with limited resources for better diagnostic accuracy. PMID- 26907097 TI - Babesia bovis and Babesia bigemina infection levels estimated by qPCR in Angus cattle from an endemic area of Sao Paulo state, Brazil. AB - The levels of infection by Babesia bovis and Babesia bigemina were estimated by absolute quantification through the quantitative PCR technique (qPCR). Fifty-one contemporaneous Angus cattle were evaluated on two occasions. The number of standard female Rhipicephalus microplus ticks present on the left side of the body was counted and blood samples were drawn from the tail vein into tubes containing the anticoagulant EDTA. The blood samples were submitted to DNA extraction and used to quantify the number of copies (NC) of DNA from B. bovis and B. bigemina by qPCR. The data on tick count and number of DNA copies were transformed for normalization and analyzed by a mixed model method. A multivariate model with repeated measures of the same animal, including the effects of collection, parasite species and their interaction, was used. The repeatability values were obtained from the matrix of (co)variances and were expressed for each species. The correlations between the counts of different species on the same animal, in the same collection or different collections, were also estimated. The results showed the qPCR could distinguish the two between infection by the two Babesia species. Infection levels by B. bovis and B. bigemina were detected in 100% and 98% of the animals, respectively. Significant differences were found (P<0.05) between the NC of the two Babesia species, B. bovis 1.49+/-0.07 vs. B. bigemina 0.82+/-0.06. Low repeatabilities were found for the counts of R. microplus and NC of B. bovis and B. bigemina: 0.05, 0.10 and 0.02, respectively. The correlations between R. microplus count and NC of B. bovis and B. bigemina were both very near zero. However, an association was observed between the NC of the two species, with a correlation coefficient of 0.30 for measures from the same collection. The absence of associations between the quantity of DNA from B. bovis and B. bigemina and the tick counts suggests that the variation of parasitemia by the hemoparasites did not depend on the tick infestation levels at the moment of each collection. The repeatability values estimated indicate that under the study conditions, the variations in the tick infestation levels and of parasitemia by B. bovis and B. bigemina depend more on factors related to each collection than on intrinsic factors of the animal. PMID- 26907096 TI - Raman Fingerprints of Atomically Precise Graphene Nanoribbons. AB - Bottom-up approaches allow the production of ultranarrow and atomically precise graphene nanoribbons (GNRs) with electronic and optical properties controlled by the specific atomic structure. Combining Raman spectroscopy and ab initio simulations, we show that GNR width, edge geometry, and functional groups all influence their Raman spectra. The low-energy spectral region below 1000 cm(-1) is particularly sensitive to edge morphology and functionalization, while the D peak dispersion can be used to uniquely fingerprint the presence of GNRs and differentiates them from other sp(2) carbon nanostructures. PMID- 26907098 TI - Consumption of dairy foods in relation to impaired glucose metabolism and type 2 diabetes mellitus: the Maastricht Study. AB - Observational studies suggest an inverse association between total dairy product intake and diabetes risk. However, there is a lack of information on the relationship of specific dairy products with impaired glucose metabolism (IGM) and type 2 diabetes mellitus (T2DM). Individuals aged 40-75 years were recruited for the Maastricht Study. All the participants filled out a 253-food item FFQ, covering fifty specific dairy items that captured differences between full-fat, semi-skimmed and skimmed products, as well as fermented and non-fermented products. Glucose metabolism status was assessed by an oral glucose tolerance test, and participants were informed on their glucose metabolism status after returning the FFQ. Data of 2391 individuals were available to estimate OR (95 % CI) for IGM (n 470) and newly diagnosed (ND) T2DM (n 125), with adjustment for age, sex, BMI, physical activity, smoking status, education, energy intake and intakes of vegetables, fruits, meat and fish. For IGM, fully adjusted analyses revealed inverse associations, with OR comparing the highest with the lowest tertile of intake of 0.73 (95 % CI 0.55, 0.96) for skimmed products and 0.74 (95 % CI 0.54, 0.99) for fermented products. These dairy products were not associated with ND T2DM. In contrast, full-fat products were positively associated with ND T2DM (OR 2.01; 95 % CI 1.16, 3.47), whereas total dairy product intake was inversely associated with ND T2DM (OR 0.50; 95 % CI 0.26, 0.93). In conclusion, individuals with a high consumption of skimmed and fermented products had lower odds of having IGM, and individuals with a high consumption of total dairy products had lower odds of having ND T2DM. High intake of full-fat products was not related to IGM but was positively related to ND T2DM. PMID- 26907099 TI - Enhanced bone regeneration with carbon nanotube reinforced hydroxyapatite in animal model. AB - In order to improve the inherently poor mechanical properties of hydroxyapatite (HAp) and to increase its feasibility as load bearing implant material, in the present investigation, functionalised (HFC1 and HFC2) and non-functionalized (HC1 and HC2) multi-walled carbon nanotubes were used as reinforcing material with HAp. Significant improvement with respect to fracture toughness, flexural strength and impact strength of the composites was noticed. In vitro biological properties of HAp-carbon nanotube (CNT) biocomposites have also favored uniform and systematic apatite growth on their surface. Subsequently, in vivo osseous ingrowth at bone defect of rabbit femur was evaluated and compared using radiology, push out test, fluorochrome labeling, histology and scanning electron microscopy after 2 and 4 months respectively. The results demonstrated growth of web like soft callus from the host bone towards the implant, ensuring strong host bone interaction. Toxicological studies of the liver and kidney cells exhibited no abnormality, thereby confirming non-toxicity of the CNT in the animal body. Host-implant biomechanical strength showed high interfacial strength of the composites, indicating their high potentials to be used for bone remodeling applications. PMID- 26907101 TI - Deep-sea whale fall fauna from the Atlantic resembles that of the Pacific Ocean. AB - Whale carcasses create remarkable habitats in the deep-sea by producing concentrated sources of organic matter for a food-deprived biota as well as places of evolutionary novelty and biodiversity. Although many of the faunal patterns on whale falls have already been described, the biogeography of these communities is still poorly known especially from basins other than the NE Pacific Ocean. The present work describes the community composition of the deepest natural whale carcass described to date found at 4204 m depth on Southwest Atlantic Ocean with manned submersible Shinkai 6500. This is the first record of a natural whale fall in the deep Atlantic Ocean. The skeleton belonged to an Antarctic Minke whale composed of only nine caudal vertebrae, whose degradation state suggests it was on the bottom for 5-10 years. The fauna consisted mainly of galatheid crabs, a new species of the snail Rubyspira and polychaete worms, including a new Osedax species. Most of the 41 species found in the carcass are new to science, with several genera shared with NE Pacific whale falls and vent and seep ecosystems. This similarity suggests the whale-fall fauna is widespread and has dispersed in a stepping stone fashion, deeply influencing its evolutionary history. PMID- 26907102 TI - Nurse-led practice is a model for change. PMID- 26907100 TI - Carbon Monoxide Gas Is Not Inert, but Global, in Its Consequences for Bacterial Gene Expression, Iron Acquisition, and Antibiotic Resistance. AB - AIMS: Carbon monoxide is a respiratory poison and gaseous signaling molecule. Although CO-releasing molecules (CORMs) deliver CO with temporal and spatial specificity in mammals, and are proven antimicrobial agents, we do not understand the modes of CO toxicity. Our aim was to explore the impact of CO gas per se, without intervention of CORMs, on bacterial physiology and gene expression. RESULTS: We used tightly controlled chemostat conditions and integrated transcriptomic datasets with statistical modeling to reveal the global effects of CO. CO is known to inhibit bacterial respiration, and we found expression of genes encoding energy-transducing pathways to be significantly affected via the global regulators, Fnr, Arc, and PdhR. Aerobically, ArcA-the response regulator is transiently phosphorylated and pyruvate accumulates, mimicking anaerobiosis. Genes implicated in iron acquisition, and the metabolism of sulfur amino acids and arginine, are all perturbed. The global iron-related changes, confirmed by modulation of activity of the transcription factor Fur, may underlie enhanced siderophore excretion, diminished intracellular iron pools, and the sensitivity of CO-challenged bacteria to metal chelators. Although CO gas (unlike H2S and NO) offers little protection from antibiotics, a ruthenium CORM is a potent adjuvant of antibiotic activity. INNOVATION: This is the first detailed exploration of global bacterial responses to CO, revealing unexpected targets with implications for employing CORMs therapeutically. CONCLUSION: This work reveals the complexity of bacterial responses to CO and provides a basis for understanding the impacts of CO from CORMs, heme oxygenase activity, or environmental sources. Antioxid. Redox Signal. 24, 1013-1028. PMID- 26907105 TI - Message of thanks is out of this world. PMID- 26907104 TI - Hundreds of senior and specialist nursing posts lost across England. PMID- 26907106 TI - Tatchell commends HIV support. PMID- 26907108 TI - RCN criticises Scottish bank staff change. PMID- 26907107 TI - NHS Improvement report shows need for 15,000 more nurses. PMID- 26907109 TI - Nurse who was dismissed from trust dies from burn injuries. PMID- 26907110 TI - Critical care professionals say intuition guides their work. PMID- 26907112 TI - Learning disability patients 'let down'. PMID- 26907113 TI - Entries invited for new cancer research award. PMID- 26907114 TI - Pressure ulcer grading wheel gets full marks. PMID- 26907115 TI - Open visiting policy contributes to drop in falls by hospital patients. PMID- 26907116 TI - Downbanded or deleted--how the NHS is shedding its senior nurses. PMID- 26907122 TI - Tuberculosis. PMID- 26907123 TI - Tackling the impact of problem drinking. AB - As the UK's drinking culture exerts increasing pressure on the NHS, nurses in settings from emergency departments to GP practices and community care are on the front line of alcohol abuse, using brief interventions and outreach education to change patients' behavior. PMID- 26907124 TI - Nurse-led general practice blazes a trail. AB - The nurse-led Cuckoo Lane Surgery in London has been rated outstanding by the Care Quality Commission. Nurses run the practice and deliver most of the care to patients. Patient satisfaction rates are very high, and staff say Cuckoo Lane is an exceptionally rewarding place to work. PMID- 26907137 TI - Doula Contraction Labor Coach app. PMID- 26907125 TI - At the vanguard of partnership working. AB - The concluding part of our series on vanguards looks at how integrating services is prompting nurses to develop and extend their roles. If the NHS is to cope with rising demand and limited resources, staff in different sectors will have to work in partnership across traditional boundaries. PMID- 26907138 TI - Government won't back down, but that's fine--because neither will we. PMID- 26907139 TI - Care is not rocket science, it is about employing the right staff. PMID- 26907140 TI - These days we don't have the luxury of 'spares' to go round. PMID- 26907141 TI - Muted protests on contracts fail nurses as well as their patients. PMID- 26907142 TI - Challenging prejudice against LGBT people a big step forward. PMID- 26907145 TI - Margaret Brooke 1915-2016. PMID- 26907146 TI - Anna Bolam 1987-2015. PMID- 26907147 TI - How to remove a pulmonary artery catheter. PMID- 26907148 TI - Establishing effective working relationships. AB - This article, the second in a series of 11, provides support and offers advice to new and existing mentors and practice teachers to enable them to progress in their role and develop a portfolio of evidence. In particular, the article discusses how to establish effective working relationships and emphasises the importance of the student-mentor or student-practice teacher relationship. It examines the essential qualities, attributes and characteristics of an effective mentor or practice teacher. The article provides learning activities and suggests ways in which mentors and practice teachers can undertake various self assessments, enabling them to gather relevant evidence to demonstrate how they can meet and maintain the requirements for these roles as stipulated by the Nursing and Midwifery Council. PMID- 26907149 TI - Developing nursing care plans. AB - This article aims to enhance nurses' understanding of nursing care plans, reflecting on the past, present and future use of care planning. This involves consideration of the central theories of nursing and discussion of nursing models and the nursing process. An explanation is provided of how theories of nursing may be applied to care planning, in combination with clinical assessment tools, to ensure that care plans are context specific and patient centred. PMID- 26907150 TI - Spirituality. PMID- 26907151 TI - Lightening the load. PMID- 26907152 TI - Life as an independent midwife. PMID- 26907154 TI - Ethical care in action. PMID- 26907155 TI - Synthesis of new secretory phospholipase A2-inhibitory indole containing isoxazole derivatives as anti-inflammatory and anticancer agents. AB - Secretory phospholipase A2 (sPLA2) is an important enzyme that plays a key role in various inflammatory diseases including cancer and its inhibitors have been developed as preventive or therapeutic agents. In the present study, a series of new indole containing isoxazole derivatives (10a-10o) is synthesized and evaluated for their sPLA2 inhibitory activities. All compounds (10a-10o) showed significant sPLA2 inhibition activities both in vitro and in vivo studies which is substantiated in in silico studies. Among all the tested compounds, 10o showed potent sPLA2 inhibition activity, that is comparable or more to ursolic acid (positive control). Further studies demonstrated that 10o showed in vitro antiproliferative activity when tested against MCF-7 breast and DU145 prostate cancer cells. Furthermore, compounds 10a-10o obeyed lipinsky's rule of 5 and suggesting druggable properties. The in vitro, in vivo and in silico results are encouraging and warrant pre-clinical studies to develop sPLA2-inhibitory compound 10o as novel therapeutic agent for various inflammatory disorders and several malignancies. PMID- 26907156 TI - Design strategies, structure activity relationship and mechanistic insights for purines as kinase inhibitors. AB - Kinases control a diverse set of cellular processes comprising of reversible phosphorylation of proteins. Protein kinases play a pivotal role in human tumor cell proliferation, migration and survival of neoplasia. In the recent past, purine based molecules have emerged as significantly potent kinase inhibitors. In view of their promising potential for the inhibition of kinases, this review article focuses on purines which have progressed as kinase inhibitors during the last five years. A detailed account of the design strategies employed for the synthesis of purine analogs exerting inhibitory effects on diverse kinases has been presented. Apart from presenting the design strategies, the article also highlights the structure activity relationship along with mechanistic insights revealed during the biological evaluation of the purine analogs for kinase inhibition. The interactions with the amino acid residues responsible for kinase inhibitory potential of purine based molecules have also been discussed. In this assemblage, purine based protein kinase inhibitors patented in the past have also been summarized in the tabular form. This compilation will be of great interest for the researchers working in the area of protein kinase inhibitors. PMID- 26907157 TI - Three stories on Eph kinase inhibitors: From in silico discovery to in vivo validation. AB - Several selective and potent EphB4 inhibitors have been discovered, optimized and biophysically characterized by our groups over the past years. On the outset of these discoveries high throughput docking techniques were applied. Herein, we review the optimization campaigns started from three of these hits (Xan-A1, Pyr A1 and Qui-A1) with emphasis on their in depth in vitro and in vivo characterization, together with previously unpublished angiogenesis and fluorescence based assays. PMID- 26907158 TI - Sequential Anaerobic/Aerobic Digestion for Enhanced Carbon/Nitrogen Removal and Cake Odor Reduction. AB - Anaerobic digestion (AD) has been proven to be an effective process for the treatment of wastewater sludge. However, it produces high levels of ammonia in the digester effluent, which may jeopardize meeting stringent nutrient discharge limits. In this study, the effect of a sequential anaerobic/aerobic (AN/AERO) digestion and a single-stage conventional AN digestion (as control) was investigated on mixed (primary + secondary) sludge generated by the Annacis Island wastewater treatment plant (WWTP) (BC, Canada). An overall sludge retention time (SRT) of 22.5 days under three different scenarios was chosen based on the current operational SRT of the digesters at the Annacis Island WWTP. The steady state results have shown that sequential AN/AERO digestion configurations achieved up to 11% higher volatile solids (VS) removal and 72% lower ammonia generation over single-stage conventional AN digestion. Furthermore, sequential AN/AERO system also showed enhanced dewaterability, improved fecal coliform destruction and reduced digested cake odors over control digesters. PMID- 26907159 TI - Systematic review: does endocrine therapy prolong survival in patients with prostate cancer? AB - Objective Primary androgen deprivation therapy (ADT) remains the gold standard in the management of patients with advanced prostate cancer (PCa). ADT relieves symptoms and reduces tumor burden, but it has never been demonstrated to increase either PCa-specific or overall survival per se. Several trials have challenged this dogma. The aim of this study was to evaluate how endocrine therapy (ET) affects survival in different clinical settings of PCa. Materials and methods A review of published phase II, III and IV studies evaluating the effect of ET on survival was performed. Results In localized and locally advanced non-metastatic PCa, neoadjuvant ET before radical prostatectomy has no effect on survival. Neoadjuvant and adjuvant ET in combination with curatively intended radiotherapy results in PCa-specific and overall survival benefit, although the duration of ET remains under debate. In N + disease, the timing of ET is under debate, although data suggest that early ET is associated with decreased PCa-specific and overall mortality. In M + disease, no proper randomized trials have been performed in patients with newly diagnosed M1 disease. In metastatic castration-resistant PCa, two novel endocrine agents have been proven to increase overall survival significantly compared to placebo. Conclusions ET has never been proven to increase survival in newly diagnosed metastatic PCa in a randomized clinical trial. Nonetheless, a number of trials supports that ET with proper timing, sequencing and in combination with other therapeutic modalities increases survival in several stages of PCa. PMID- 26907160 TI - Expanding the Scope of Primary Amine Catalysis: Stereoselective Synthesis of Indanedione-Fused 2,6-Disubstituted trans-Spirocyclohexanones. AB - A cinchona-alkaloid-derived chiral primary-amine-catalyzed enantioselective method for the synthesis of the thermodynamically less stable indanedione-fused 2,6-trans-disubstituted spirocyclohexanones is demonstrated. Both the enantiomeric forms of the trans isomer are obtained in excellent yields and enantioselectivities. Furthermore, one of the enantiopure trans-spiranes bearing an additional alpha-substitution on the cyclohexanone ring was then epimerized into its thermodynamically stable cis counterpart, with little loss of enantioselectivity to demonstrate the feasibility of such a transformation. Mechanistic investigations revealed two competing pathways, a concerted Diels Alder reaction and a stepwise Michael addition, for the formation of corresponding products. PMID- 26907161 TI - Structures of Trypanosome Vacuolar Soluble Pyrophosphatases: Antiparasitic Drug Targets. AB - Trypanosomatid parasites are the causative agents of many neglected tropical diseases, including the leishmaniases, Chagas disease, and human African trypanosomiasis. They exploit unusual vacuolar soluble pyrophosphatases (VSPs), absent in humans, for cell growth and virulence and, as such, are drug targets. Here, we report the crystal structures of VSP1s from Trypanosoma cruzi and T. brucei, together with that of the T. cruzi protein bound to a bisphosphonate inhibitor. Both VSP1s form a hybrid structure containing an (N-terminal) EF-hand domain fused to a (C-terminal) pyrophosphatase domain. The two domains are connected via an extended loop of about 17 residues. Crystallographic analysis and size exclusion chromatography indicate that the VSP1s form tetramers containing head-to-tail dimers. Phosphate and diphosphate ligands bind in the PPase substrate-binding pocket and interact with several conserved residues, and a bisphosphonate inhibitor (BPH-1260) binds to the same site. On the basis of Cytoscape and other bioinformatics analyses, it is apparent that similar folds will be found in most if not all trypanosomatid VSP1s, including those found in insects (Angomonas deanei, Strigomonas culicis), plant pathogens (Phytomonas spp.), and Leishmania spp. Overall, the results are of general interest since they open the way to structure-based drug design for many of the neglected tropical diseases. PMID- 26907162 TI - Confidence through consensus: a neural mechanism for uncertainty monitoring. AB - Models that integrate sensory evidence to a threshold can explain task accuracy, response times and confidence, yet it is still unclear how confidence is encoded in the brain. Classic models assume that confidence is encoded in some form of balance between the evidence integrated in favor and against the selected option. However, recent experiments that measure the sensory evidence's influence on choice and confidence contradict these classic models. We propose that the decision is taken by many loosely coupled modules each of which represent a stochastic sample of the sensory evidence integral. Confidence is then encoded in the dispersion between modules. We show that our proposal can account for the well established relations between confidence, and stimuli discriminability and reaction times, as well as the fluctuations influence on choice and confidence. PMID- 26907163 TI - The effectiveness and cost-effectiveness of erythropoiesis-stimulating agents (epoetin and darbepoetin) for treating cancer treatment-induced anaemia (including review of technology appraisal no. 142): a systematic review and economic model. AB - BACKGROUND: Anaemia is a common side effect of cancer treatments and can lead to a reduction in quality of life. Erythropoiesis-stimulating agents (ESAs) are licensed for use in conjunction with red blood cell transfusions to improve cancer treatment-induced anaemia (CIA). OBJECTIVE: To investigate the effectiveness and cost-effectiveness of ESAs in anaemia associated with cancer treatment (specifically chemotherapy). DATA SOURCES: The following databases were searched from 2004 to 2013: The Cochrane Library, MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Web of Science, Cumulative Index to Nursing and Allied Health Literature, British Nursing Index, Health Management Information Consortium, Current Controlled Trials and ClinicalTrials.gov. The US Food and Drug Administration and European Medicines Agency websites were also searched. Bibliographies of included papers were scrutinised for further potentially includable studies. REVIEW METHODS: The clinical effectiveness review followed principles published by the NHS Centre for Reviews and Dissemination. Randomised controlled trials (RCTs), or systematic reviews of RCTs, of ESAs (epoetin or darbepoetin) for treating people with CIA were eligible for inclusion in the review. Comparators were best supportive care, placebo or other ESAs. Anaemia- and malignancy-related outcomes, health-related quality of life (HRQoL) and adverse events (AEs) were evaluated. When appropriate, data were pooled using meta-analysis. An empirical health economic model was developed comparing ESA treatment with no ESA treatment. The model comprised two components: one evaluating short-term costs and quality-adjusted life-years (QALYs) (while patients are anaemic) and one evaluating long-term QALYs. Costs and benefits were discounted at 3.5% per annum. Probabilistic and univariate deterministic sensitivity analyses were performed. RESULTS: Of 1457 titles and abstracts screened, 23 studies assessing ESAs within their licensed indication (based on start dose administered) were included in the review. None of the RCTs were completely aligned with current European Union licenses. The results suggest a clinical benefit from ESAs for anaemia-related outcomes and an improvement in HRQoL scores. The impact of ESAs on AEs and survival remains highly uncertain, although point estimates are lower, confidence intervals are wide and not statistically significant. Base-case incremental cost-effectiveness ratios (ICERs) for ESA treatment compared with no ESA treatment ranged from L 19,429 to L 35,018 per QALY gained, but sensitivity and scenario analyses demonstrate considerable uncertainty in these ICERs, including the possibility of overall health disbenefit. All ICERs were sensitive to survival and cost. LIMITATIONS: The relative effectiveness of ESAs was not addressed; all ESAs were assumed to have equivalent efficacy. No studies were completely aligned with their European labelling beyond the starting dose evaluated. There is questionable generalisability given that the included trials were published >20 years ago and there have been many changes to chemotherapy as well as to the quality of supportive treatment. Trial quality was moderate or poor and there was considerable unexplained heterogeneity for a number of outcomes, particularly survival, and evidence of publication bias. Adjustments were not made to account for multiple testing. CONCLUSIONS: ESAs could be cost-effective when used closer to licence, but there is considerable uncertainty, mainly because of unknown impacts on overall survival. STUDY REGISTRATION: This study is registered as PROSPERO CRD42013005812. FUNDING: The National Institute for Health Research Health Technology Assessment programme. PMID- 26907167 TI - Benign adult familial myoclonus epilepsy is a progressive disorder: no longer idiopathic generalized epilepsy. AB - Brain dysfunction in Japanese benign adult familial myoclonus epilepsy (BAFME) has not been elucidated. To clarify diffuse brain dysfunction as indicated by posterior dominant rhythm (PDR) slowing in patients with BAFME. The frequency of PDR on EEG was studied in 19 BAFME patients (50.6+/-15.7 years) and 38 age matched control subjects (50.1+/-14.5 years). We investigated the relationship between age and PDR in both groups. PDR frequency in the patient group (9.1+/-0.7 Hz) was significantly slower than that of age-matched control subjects (10.4+/ 1.1 Hz; p<0.0001), regardless of the use of anticonvulsants. There was no significant difference in PDR slowing with age between groups. These findings suggest that Japanese patients with BAFME have mild diffuse brain dysfunction with minimal progression. PMID- 26907168 TI - Can We Just Rely on Contrast? PMID- 26907169 TI - Cardiac Computed Tomography Angiography for Left Atrial Appendage Closure. AB - Atrial fibrillation is prevalent and percutaneous left atrial appendage (LAA) closure is increasingly performed worldwide. This procedure is technically challenging and the success and procedural complexities depend on anatomy of the LAA and surrounding structures. These are readily depicted on cardiac computed tomography angiography (CCTA), which offers unique imaging planes. CCTA allows not only preplanning anatomic LAA assessment, but can also be used to evaluate for pre-existing LAA thrombus, and done postprocedure for surveillance for device related thrombus, residual leak, and complications. In this article, we review the practical utility of CCTA for LAA closure. PMID- 26907170 TI - Effect of Ag/Au bilayer assisted etching on the strongly enhanced photoluminescence and visible light photocatalysis by Si nanowire arrays. AB - We report on the strongly enhanced photoluminescence (PL) and visible light photocatalysis by arrays of vertically aligned single crystalline Si nanowires (NWs) grown by Ag/Au bilayer assisted etching. High resolution FESEM and TEM imaging reveals that the Si NWs are decorated with ultra-small size arbitrary shaped Si nanocrystals (NCs) due to the lateral etching of the NWs. A strong broad band and tunable visible to near-infrared (NIR) photoluminescence (PL) in the range 1.3-2.4 eV are observed for these Si NWs/NCs at room temperature, depending on the etching conditions. Our studies reveal that the visible-NIR PL intensity is about two orders of magnitude higher and it exhibits faster decay dynamics in the bilayer assisted etching case as compared to the Ag or Au single layer etching case. The enhanced PL in the bimetal case is attributed to the longer length and higher density of the Si NWs/NCs, surface plasmon resonance enhanced absorption by residual bimetal NPs and the enhanced radiative recombination rate. Studies on the time evolution of PL spectral features with laser exposure under ambient conditions and laser power dependence reveal that both the quantum confinement of carriers in Si NCs and the nonbridging oxygen hole defects in the SiOx layer contribute to the tunable PL. Interestingly, Si NWs grown by Ag/Au bilayer assisted etching exhibit enhanced photocatalytic degradation of methylene blue in comparison to Si NWs grown by single layer Ag or Au assisted etching. The Schottky barrier present between bimetallic NPs and nanoporous Si NWs with Si-H bonds facilitates the photocatalytic activity by efficient separation of photogenerated e-h pairs. Our results demonstrate the superiority of the Si NW array grown by bilayer assisted etching for their cutting edge applications in optoelectronics and environmental cleaning. PMID- 26907171 TI - The exposure of the Great Barrier Reef to ocean acidification. AB - The Great Barrier Reef (GBR) is founded on reef-building corals. Corals build their exoskeleton with aragonite, but ocean acidification is lowering the aragonite saturation state of seawater (Omegaa). The downscaling of ocean acidification projections from global to GBR scales requires the set of regional drivers controlling Omegaa to be resolved. Here we use a regional coupled circulation-biogeochemical model and observations to estimate the Omegaa experienced by the 3,581 reefs of the GBR, and to apportion the contributions of the hydrological cycle, regional hydrodynamics and metabolism on Omegaa variability. We find more detail, and a greater range (1.43), than previously compiled coarse maps of Omegaa of the region (0.4), or in observations (1.0). Most of the variability in Omegaa is due to processes upstream of the reef in question. As a result, future decline in Omegaa is likely to be steeper on the GBR than currently projected by the IPCC assessment report. PMID- 26907172 TI - Transketolase-like 1 ectopic expression is associated with DNA hypomethylation and induces the Warburg effect in melanoma cells. AB - BACKGROUND: The metabolism of cancer cells is often reprogrammed by dysregulation of metabolic enzymes. Transketolase-like 1 (TKTL1) is a homodimeric transketolase linking the pentose-phosphate pathway with the glycolytic pathway. It is generally silenced at a transcriptional level in somatic tissues. However, in human cancers its expression is associated with the acquisition of a glycolytic phenotype (the Warburg effect) by cancer cells that contributes to the progression of malignant tumors. In melanoma, defective promoter methylation results in the expression of genes and their products that can affect the tumor cell's phenotype including the modification of immune and functional characteristics. The present study evaluates the role of TKTL1 as a mediator of disease progression in melanoma associated with a defective methylation phenotype. METHODS: The expression of TKTL1 in metastatic melanoma tumors and cell lines was analysed by qRT-PCR and immunohistochemistry. The promoter methylation status of TKTL1 in melanoma cells was evaluated by quantitative methylation specific PCR. Using qRT-PCR, the effect of a DNA demethylating agent 5-aza-2'-deoxycytidine (5aza) on the expression of TKTL1 was examined. Biochemical and molecular analyses such as glucose consumption, lactate production, invasion, proliferation and cell cycle progression together with ectopic expression and siRNA mediated knockdown were used to investigate the role of TKTL1 in melanoma cells. RESULTS: Expression of TKTL1 was highly restricted in normal adult tissues and was overexpressed in a subset of metastatic melanoma tumors and derived cell lines. The TKTL1 promoter was activated by hypomethylation and treatment with 5aza induced TKTL1 expression in melanoma cells. Augmented expression of TKTL1 in melanoma cells was associated with a glycolytic phenotype. Loss and gain of function studies revealed that TKTL1 contributed to enhanced invasion of melanoma cells. CONCLUSIONS: Our data provide evidence for an important role of TKTL1 in aerobic glycolysis and tumor promotion in melanoma that may result from defective promoter methylation. This epigenetic change may enable the natural selection of tumor cells with a metabolic phenotype and thereby provide a potential therapeutic target for a subset of melanoma tumors with elevated TKTL1 expression. PMID- 26907173 TI - Pharmacology of the Adenosine A3 Receptor in the Vasculature and Essential Hypertension. AB - BACKGROUND: Essential hypertension is considered to be a multifactorial disorder and its aetiology has yet to be clearly identified. As the adenosine receptors have a significant role in mediating vasodilation, alterations in their structures or signalling pathways may be involved in the development of hypertension. This study aimed to measure the expression of adenosine A3 receptors in a range of cardiovascular tissues and determine whether they could be altered with essential hypertension, and to functionally test responses to adenosine A3 receptor agonists in coronary blood vessels using the isolated perfused heart preparation. METHODS: mRNA samples from cardiovascular tissues and a range of blood vessels were collected from 10 week old male spontaneously hypertensive rats and age-gender matched Wistar rats (n = 8). The Langendorff heart perfusion preparation was used to characterise adenosine A3 receptor mediated coronary vasodilation in the rat heart. RESULTS: Adenosine A3 receptor agonists induced coronary vasodilation. The expression of adenosine A3 receptors in cardiovascular tissues was altered in a tissue-specific pattern. Specifically, down-regulation of adenosine A3 receptor expression occurred in hypertensive hearts, which might be associated with attenuated vasodilator responses observed in coronary vessels to adenosine A3 receptor agonists. CONCLUSIONS: This study demonstrated alterations in the expression of adenosine A3 receptors occurred in a tissue specific mode, and reduced adenosine A3 receptor mediated coronary vasodilation in hearts from spontaneously hypertensive rats. Our findings with regard to changes in the adenosine A3 receptor in hypertensive hearts suggest that adenosine A3 receptor might play a role in the physiopathology of essential hypertension and potentially open the way to pharmacologic manipulation of vasomotor activity by the use of adenosine A3 receptor agonists. PMID- 26907174 TI - [Does urinary sacral neuromodulation improve bowel symptoms other than fecal incontinence: A systematic review]. AB - PURPOSE: To evaluate literature data about urinary sacral neuromodulation and its effects on bowel symptoms other than fecal incontinence. METHOD: A systematic review was conducted using PubMed/Medline with the following keywords: sacral neuromodulation, urinary incontinence, voiding symptoms, intestinal bowel syndrome, constipation, epidemiology. RESULTS: Urinary SNS seems to improve intestinal bowel symptoms scores (level of evidence 4). However, for constipation, there are more contrasting results. If symptoms scores seem to improve, QOL scores are not significantly changed. Furthermore, some people reported an aggravation of their constipation symptoms (level of evidence 4). Those contrasted results could be explained by the various causes of constipation which implies various pathophysiological pathways. CONCLUSIONS: A better evaluation of digestive symptoms in patient candidate to urinary SNS could help identifying patients able to be improve by SNS. LEVEL OF EVIDENCE: 4. PMID- 26907175 TI - Effect of turmeric on colon histology, body weight, ulcer, IL-23, MPO and glutathione in acetic-acid-induced inflammatory bowel disease in rats. AB - BACKGROUND: This study investigates the protective effects of turmeric (Curcuma longa, CL) on acetic acid-induced colitis in rats. METHOD: Inflammatory bowel disease (IBD) was induced in male Wistar rats by intra-rectal administration of 1 ml of 4% acetic acid at 8 cm proximal to the anus for 30 s. Curcuma longa (CL) powder, (1, 10, or 100 mg/kg/day) was administered for either 3 days before or after IBD for 7 days. The body weight, macroscopic and microscopic analysis of the colon of CL-treated IBD rats and that of control rats (no IBD, no CL) were performed on 0 day, 2, 4 and 7th day. Myeloperoxidase (MPO), IL-23 and glutathione levels in control, untreated and treated rats were measured by ELISA. RESULTS: CL significantly (P < 0.05) improved IBD-induced reduction in mean body weight and mean macroscopic ulcer score. Administration of CL also significantly (P < 0.01) reduced the mean microscopic ulcer score when compared to untreated IBD control. Intake of CL by rats resulted in a significant (P < 0.05) increase in the mean serum glutathione level compared to untreated control. CL reduced both MPO and IL-23 levels in the colonic mucosa of the rat. CONCLUSION: CL improved body weight gain, mean macroscopic and microscopic ulcer scores in the colon of rats suffering from acetic acid-induced IBD. CL reduced both MPO and IL 23 in the mucosa of the colon. The increase in the mean serum glutathione level may help in the reduction of oxidative stress associated with IBD. PMID- 26907176 TI - Unique plasma metabolomic signatures of individuals with inherited disorders of long-chain fatty acid oxidation. AB - Blood and urine acylcarnitine profiles are commonly used to diagnose long-chain fatty acid oxidation disorders (FAOD: i.e., long-chain hydroxy-acyl-CoA dehydrogenase [LCHAD] and carnitine palmitoyltransferase 2 [CPT2] deficiency), but the global metabolic impact of long-chain FAOD has not been reported. We utilized untargeted metabolomics to characterize plasma metabolites in 12 overnight-fasted individuals with FAOD (10 LCHAD, two CPT2) and 11 healthy age-, sex-, and body mass index (BMI)-matched controls, with the caveat that individuals with FAOD consume a low-fat diet supplemented with medium-chain triglycerides (MCT) while matched controls consume a typical American diet. In plasma 832 metabolites were identified, and partial least squared-discriminant analysis (PLS-DA) identified 114 non-acylcarnitine variables that discriminated FAOD subjects and controls. FAOD individuals had significantly higher triglycerides and lower specific phosphatidylethanolamines, ceramides, and sphingomyelins. Differences in phosphatidylcholines were also found but the directionality differed by metabolite species. Further, there were few differences in non-lipid metabolites, indicating the metabolic impact of FAOD specifically on lipid pathways. This analysis provides evidence that LCHAD/CPT2 deficiency significantly alters complex lipid pathway flux. This metabolic signature may provide new clinical tools capable of confirming or diagnosing FAOD, even in subjects with a mild phenotype, and may provide clues regarding the biochemical and metabolic impact of FAOD that is relevant to the etiology of FAOD symptoms. PMID- 26907177 TI - Residual N-acetyl-alpha-glucosaminidase activity in fibroblasts correlates with disease severity in patients with mucopolysaccharidosis type IIIB. AB - BACKGROUND: Mucopolysaccharidosis type IIIB (MPS IIIB) is a rare genetic disorder in which the deficiency of the lysosomal enzyme N-acetyl-alpha-glucosaminidase (NAGLU) results in the accumulation of heparan sulfate (HS), leading to progressive neurocognitive deterioration. In MPS IIIB a wide spectrum of disease severity is seen. Due to a large allelic heterogeneity, establishing genotype phenotype correlations is difficult. However, reliable prediction of the natural course of the disease is needed, in particular for the assessment of the efficacy of potential therapies. METHODS: To identify markers that correlate with disease severity, all Dutch patients diagnosed with MPS IIIB were characterised as either rapid (RP; classical, severe phenotype) or slow progressors (SP; non-classical, less severe phenotype), based on clinical data. NAGLU activity and HS levels were measured in patients' fibroblasts after culturing at different temperatures. RESULTS: A small, though significant difference in NAGLU activity was measured between RP and SP patients after culturing at 37 degrees C (p < 0.01). Culturing at 30 degrees C resulted in more pronounced and significantly higher NAGLU activity levels in SP patients (p < 0.001) with a NAGLU activity of 0.58 nmol.mg 1.hr-1 calculated to be the optimal cut-off value to distinguish between the groups (sensitivity and specificity 100 %). A lower capacity of patients' fibroblasts to increase NAGLU activity at 30 degrees C could significantly predict for the loss of several disease specific functions. CONCLUSION: NAGLU activity in fibroblasts cultured at 30 degrees C can be used to discriminate between RP and SP MPS IIIB patients and the capacity of cells to increase NAGLU activity at lower temperatures correlates with disease symptoms. PMID- 26907178 TI - How Do Tracking and Changes in Dietary Pattern during Adolescence Relate to the Amount of Body Fat in Early Adulthood? AB - BACKGROUND: Few studies have addressed the influence of dietary patterns (DP) during adolescence on the amount of body fat in early adulthood. OBJECTIVE: To analyze the associations between DP tracking and changes in the period between 15 and 18 years of age and the percentage of body fat (%BF) at age 18 years. METHODS: We used data from 3,823 members of the 1993 Pelotas (Brazil) birth cohort. Body density was measured at age 18 years by air displacement plethysmograph (BOD POD) and the %BF was calculated applying the Siri equation. Based on the estimates from the FFQ, we identified DP at ages 15 ("Varied", "Traditional", "Dieting" and "Processed meats") and 18 years ("Varied", "Traditional", "Dieting" and "Fish, fast food and alcohol"). The DP tracking was defined as the individual's adherence to the same DP at both ages. Associations were tested using multiple linear regression models stratified by sex. RESULTS: The mean %BF was 25.0% (95% CI: 24.7 to 25.4), significantly greater for girls than boys (p<0.001). The adherence to any DP at age 15 years was not associated with the %BF at age 18 years. However, individuals who adhered to a "Dieting" DP at age 18 years showed greater %BF (1.30 and 1.91 percentage points in boys and girls, respectively) in comparison with those who adhered to a "Varied" DP. Boys who presented tracking of a "Dieting" DP presented greater average %BF in comparison with others DP, as well as girls who changed from the "Traditional" or "Processed meats" DP to a "Dieting" DP. CONCLUSION: These results may support public health policies and strategies focused on improving dietary habits of adolescents and young adults and preventing accumulation of body fat, especially among the adolescents with restrictive dietary habits. PMID- 26907179 TI - Direct Analysis of Amphetamine Stimulants in a Whole Urine Sample by Atmospheric Solids Analysis Probe Tandem Mass Spectrometry. AB - Amphetamine-type stimulants (ATS) are among illicit stimulant drugs that are most often used worldwide. A major challenge is to develop a fast and efficient methodology involving minimal sample preparation to analyze ATS in biological fluids. In this study, a urine pool solution containing amphetamine, methamphetamine, ephedrine, sibutramine, and fenfluramine at concentrations ranging from 0.5 pg/mL to 100 ng/mL was prepared and analyzed by atmospheric solids analysis probe tandem mass spectrometry (ASAP-MS/MS) and multiple reaction monitoring (MRM). A urine sample and saliva collected from a volunteer contributor (V1) were also analyzed. The limit of detection of the tested compounds ranged between 0.002 and 0.4 ng/mL in urine samples; the signal-to noise ratio was 5. These results demonstrated that the ASAP-MS/MS methodology is applicable for the fast detection of ATS in urine samples with great sensitivity and specificity, without the need for cleanup, preconcentration, or chromatographic separation. Thus ASAP-MS/MS could potentially be used in clinical and forensic toxicology applications. PMID- 26907181 TI - Term and Preterm Infants. PMID- 26907182 TI - Acute Renal Failure in Transplanted Kidneys. AB - Free radical-mediated injury releases proinflammatory cytokines and activates innate immunity. It has been suggested that the early innate response and the ischemic tissue damage play roles in the development of adaptive responses, which may lead to acute kidney rejection. Various durations of hypothermic kidney storage before transplantation add to ischemic tissue damage. The final stage of ischemic injury occurs during reperfusion that develops hours or days after the initial insult. Repair and regeneration processes occur together with cellular apoptosis, autophagy and necrosis and a favorable outcome is expected if regeneration prevails. Along the entire transplantation time course, there is a great demand for novel immune and nonimmune injury biomarkers. The use of these markers can be of great help in the monitoring of kidney injury in potential kidney donors, where acute kidney damage can be overlooked, in predicting acute transplant dysfunction during the early post-transplant periods, or in predicting chronic changes in long term followup. Numerous investigations have demonstrated that biomarkers that have the highest predictive value in acute kidney injury include NGAL, Cystatin C, KIM-1, IL-18, and L-FABP. Most investigations show that the ideal biomarker to fulfill all the needs in renal transplant has not been identified yet. Although, in many animal models, new biomarkers are emerging for predicting acute and chronic allograft damage, in human allograft analysis they are still not routinely accepted and renal biopsy still remains the gold standard. PMID- 26907180 TI - microRNA 338-3p exhibits tumor suppressor role and its down-regulation is associated with adverse clinical outcome in prostate cancer patients. AB - MicroRNAs (miRNAs) are small non-coding RNAs that function in transcriptional and post-transcriptional regulation of gene expression. Several miRNAs have been implicated in regulating prostate cancer (PCa) progression. Deregulations of miRNA regulatory networks have been reported in ERG positive PCa, which accounts for ~50 % of PCa and have been suggested to affect tumor aggressiveness. The function of miR338-3p, its prognostic significance, and its association with ERG positive PCa has not been fully investigated. Using microarray expression profiling, we identified miRNA338-3p as among the top deregulated miRNAs associated with ERG status in PCa. We investigated miR338-3p function using in vitro and in vivo experimental models and its expression was assessed and validated in clinical samples and a public cohort of localized and metastatic prostate cancer. miR338-3p was significantly down-regulated with disease progression from benign prostate tissue to primary and metastatic lesions. In localized disease, patients with lower miR338-3p expression levels showed increased association to biochemical recurrence and several adverse pathological parameters compared to patients with higher miRNA338-3p tissue expression levels. Using in vitro PCa cell models, overexpression of miR338-3p resulted in a decrease in cell invasion and expression of chemokine signalling genes CXCL12, CXCR4, and CXCR7. In vivo, orthotropic implantation of PC3 cells stably expressing miR338-3p was associated with a significant decrease in tumor weights compared to control cells. miR338-3p has anti-proliferative and anti-invasive properties. It affects CXCR4 axis, and its down-regulation is associated with adverse clinical outcomes in PCa patients. PMID- 26907183 TI - Is the timing of recommended childhood vaccines evidence based? PMID- 26907185 TI - Menstrual Disturbances in Premenopausal Women with End-Stage Renal Disease: A Cross-Sectional Study. AB - OBJECTIVE: To evaluate menstrual disturbances and sex hormonal status in premenopausal women with end-stage renal disease (ESRD). SUBJECTS AND METHODS: The study consisted of 184 patients with ESRD treated with one of four treatment modalities (46/modality): conventional hemodialysis (CHD), continuous ambulatory peritoneal dialysis (CAPD), nocturnal hemodialysis (NHD) and renal transplantation (RT). Blood samples were collected to determine sex hormone levels. Sociodemographic and clinical data were collected from medical records. A questionnaire was administered to analyze menstrual patterns, and the final analysis included 46, 43, 40 and 36 patients in the CHD, CAPD, NHD and RT groups, respectively. RESULTS: The overall prevalence of menstrual disturbances was 64.2% for all four treatment modalities (RT: 50%; NHD: 55%; CAPD: 72.1%, and CHD: 76.1%). Serum prolactin levels were significantly lower (p < 0.01) in the NHD (25.1 +/- 10.9 ng/ml) and RT (13.4 +/- 5.1 ng/ml) groups than in the CHD group (55.2 +/- 10.8 ng/ml). Serum progesterone levels were significantly higher (p < 0.01) in the NHD (25.7 +/- 8.3 nmol/l) and RT (30.1 +/- 5.9 nmol/l) groups than in the CHD group (17.7 +/- 7.3 nmol/l). Moreover, the hormonal status (follicle stimulating hormone, luteinizing hormone and testosterone) was much closer to normal in the NHD and RT groups compared to the other two groups. CONCLUSIONS: In this study, successful transplantation and NHD partially improved the symptoms of menstrual disturbances. Therefore, we recommend that further studies are necessary to confirm our finding in ESRD patients. PMID- 26907186 TI - Universality of vibrational spectra of globular proteins. AB - It is shown that the density of modes of the vibrational spectrum of globular proteins is universal, i.e. regardless of the protein in question, it closely follows one universal curve. The present study, including 135 proteins analyzed with a full atomic empirical potential (CHARMM22) and using the full complement of all atoms Cartesian degrees of freedom, goes far beyond previous claims of universality, confirming that universality holds even in the frequency range that is well above 100 cm(-1) (300-4000 cm(-1)), where peaks and turns in the density of states are faithfully reproduced from one protein to the next. We also characterize fluctuations of the spectral density from the average, paving the way to a meaningful discussion of rare, unusual spectra and the structural reasons for the deviations in such 'outlier' proteins. Since the method used for the derivation of the vibrational modes (potential energy formulation, set of degrees of freedom employed, etc) has a dramatic effect on the spectral density, another significant implication of our findings is that the universality can provide an exquisite tool for assessing and improving the quality of potential functions and the quality of various models used for NMA computations. Finally, we show that the input configuration also affects the density of modes, thus emphasizing the importance of simplified potential energy formulations that are minimized at the outset. In summary, our findings call for a serious two-way dialogue between theory and experiment: experimental spectra of proteins could now guide the fine tuning of theoretical empirical potentials, and the various features and peaks observed in theoretical studies--being universal, and hence now rising in importance--would hopefully spur experimental confirmation. PMID- 26907184 TI - Ertapenem for the treatment of bloodstream infections due to ESBL-producing Enterobacteriaceae: a multinational pre-registered cohort study. AB - OBJECTIVES: Data about the efficacy of ertapenem for the treatment of bloodstream infections (BSI) due to ESBL-producing Enterobacteriaceae (ESBL-E) are limited. We compared the clinical efficacy of ertapenem and other carbapenems in monomicrobial BSI due to ESBL-E. METHODS: A multinational retrospective cohort study (INCREMENT project) was performed (ClinicalTrials.gov identifier: NCT01764490). Patients given monotherapy with ertapenem or other carbapenems were compared. Empirical and targeted therapies were analysed. Propensity scores were used to control for confounding; sensitivity analyses were performed in subgroups. The outcome variables were cure/improvement rate at day 14 and all cause 30 day mortality. RESULTS: The empirical therapy cohort (ETC) and the targeted therapy cohort (TTC) included 195 and 509 patients, respectively. Cure/improvement rates were 90.6% with ertapenem and 75.5% with other carbapenems (P = 0.06) in the ETC and 89.8% and 82.6% (P = 0.02) in the TTC, respectively; 30 day mortality rates were 3.1% and 23.3% (P = 0.01) in the ETC and 9.3% and 17.1% (P = 0.01) in the TTC, respectively. Adjusted ORs (95% CI) for cure/improvement with empirical and targeted ertapenem were 1.87 (0.24-20.08; P = 0.58) and 1.04 (0.44-2.50; P = 0.92), respectively. For the propensity-matched cohorts it was 1.18 (0.43-3.29; P = 0.74). Regarding 30 day mortality, the adjusted HR (95% CI) for targeted ertapenem was 0.93 (0.43-2.03; P = 0.86) and for the propensity matched cohorts it was 1.05 (0.46-2.44; P = 0.90). Sensitivity analyses were consistent except for patients with severe sepsis/septic shock, which showed a non-significant trend favouring other carbapenems. CONCLUSIONS: Ertapenem appears as effective as other carbapenems for empirical and targeted therapy of BSI due to ESBL-E, but further studies are needed for patients with severe sepsis/septic shock. PMID- 26907188 TI - Atypical glandular cells and risk of cervical cancer. PMID- 26907187 TI - Mind the gap: TB trends in the USA and the UK, 2000-2011. AB - BACKGROUND: TB remains a major public health concern, even in low-incidence countries like the USA and the UK. Over the last two decades, cases of TB reported in the USA have declined, while they have increased substantially in the UK. We examined factors associated with this divergence in TB trends between the two countries. METHODS: We analysed all cases of TB reported to the US and UK national TB surveillance systems from 1 January 2000 through 31 December 2011. Negative binominal regression was used to assess potential demographic, clinical and risk factor variables associated with differences in observed trends. FINDINGS: A total of 259,609 cases were reported. From 2000 to 2011, annual TB incidence rates declined from 5.8 to 3.4 cases per 100,000 in the USA, whereas in the UK, TB incidence increased from 11.4 to 14.4 cases per 100,000. The majority of cases in both the USA (56%) and the UK (64%) were among foreign-born persons. The number of foreign-born cases reported in the USA declined by 15% (7731 in 2000 to 6564 in 2011) while native-born cases fell by 54% (8442 in 2000 to 3883 in 2011). In contrast, the number of foreign-born cases reported in the UK increased by 80% (3380 in 2000 to 6088 in 2011), while the number of native-born cases remained largely unchanged (2158 in 2000 to 2137 in 2011). In an adjusted negative binomial regression model, significant differences in trend were associated with sex, age, race/ethnicity, site of disease, HIV status and previous history of TB (p<0.01). Among the foreign-born, significant differences in trend were also associated with time since UK or US entry (p<0.01). INTERPRETATION: To achieve TB elimination in the UK, a re-evaluation of current TB control policies and practices with a focus on foreign-born are needed. In the USA, maintaining and strengthening control practices are necessary to sustain the progress made over the last 20 years. PMID- 26907189 TI - IRF4 SNP is predictive of melanoma subtypes. PMID- 26907190 TI - Highly selective non-opioid kappa opioid receptor (KOR) agonist salvinorin A protects against forebrain ischemia-induced brain injury in rats. AB - OBJECTIVE: To investigate the effect of salvinorin A (SA) on brain injury and neurologic function post-brain ischemia/reperfusion (I/R) using a rat forebrain ischemia model and further explore the effect of kappa opioid receptor (KOR) inhibition by SA on aquaporin-4 (AQP4) expression in the hippocampus, cortex and striatum in the forebrain. METHODS: A forebrain ischemia model was established by colligating the bilateral common carotid arteries of SD rats for 10 min. The rats were randomized to receive dimethyl sulfoxide (DMSO), SA (1 ug/100g body weight) or SA (onset of ischemia) plus SA antagonist nor-BIN (0.2 mg/100g body weight. Rat brain water content was measured. Apoptotic neurons in the hippocampal CA1 region, cortex and striatum were enumerated. AQP4 in CA1, the cortex and the striatum were determined by immunoblotting assays and immunohistochemistry at 24h post-ischemia. Neuromotor tests were performed on day 1, 2 and 5 post-ischemia. Water maze test was carried out on the 5th post-ischemia day. RESULTS: SA significantly attenuated I/R-induced increase in brain water content. Our immunoblotting assays and immunohistochemistry further revealed that SA effectively lessened I/R-induced upregulation of AQP4 expression in the hippocampus, cortex and striatum 24h post-ischemia. SA also significantly reduced the percentage of dead and apoptotic neurons in these regions compared to DMSO. Moreover, SA partially reversed I/R-induced decline in rat motor function and cognition. The neuroprotective effects of SA were partially abolished by nor-BIN. CONCLUSION: SA protects against I/R-induced brain injury by attenuating brain edema formation and inhibiting neuronal death and improves neurologic recovery of rats post-I/R. PMID- 26907191 TI - Age-dependent increase of blood-brain barrier permeability and neuron-binding autoantibodies in S100B knockout mice. AB - S100B is a calcium-sensor protein that impacts multiple signal transduction pathways. It is widely considered to be an important biomarker for several neuronal diseases as well as blood-brain barrier (BBB) breakdown. In this report, we demonstrate a BBB deficiency in mice that lack S100B through detection of leaked Immunoglobulin G (IgG) in the brain parenchyma. IgG leaks and IgG-binding to selected neurons were observed in S100B knockout (S100BKO) mice at 6 months of age but not at 3 months. By 9 months, IgG leaks persisted and the density of IgG bound neurons increased significantly. These results reveal a chronic increase in BBB permeability upon aging in S100BKO mice for the first time. Moreover, coincident with the increase in IgG-bound neurons, autoantibodies targeting brain proteins were detected in the serum via western blots. These events were concurrent with compromise of neurons, increase of activated microglia and lack of astrocytic activation as evidenced by decreased expression of microtubule associated protein type 2 (MAP2), elevated number of CD68 positive cells and unaltered expression of glial fibrillary acidic protein (GFAP) respectively. Results suggest a key role for S100B in maintaining BBB functional integrity and, further, propose the S100BKO mouse as a valuable model system to explore the link between chronic functional compromise of the BBB, generation of brain-reactive autoantibodies and neuronal dysfunctions. PMID- 26907192 TI - Highly efficient hydrogen generation from formic acid using a reduced graphene oxide-supported AuPd nanoparticle catalyst. AB - Highly dispersed AuPd alloy nanoparticles have been successfully immobilized on reduced graphene oxide (rGO) using a facile non-noble metal sacrificial method, which exhibit the highest activity at 323 K (turnover frequency, 4840 h(-1)) for hydrogen generation without CO impurity from the formic acid/sodium formate system. PMID- 26907193 TI - Cross-education of strength has a positive impact on post-stroke rehabilitation: a systematic literature review. AB - BACKGROUND: Since its discovery in 1894 cross-education of strength - a bilateral adaptation after unilateral training - has been shown to be effective in the rehabilitation after one-sided orthopedic injuries. Limited knowledge exists on its application within the rehabilitation after stroke. This review examined the evidence regarding the implication of cross-education in the rehabilitation of the post-stroke hemiplegic patient and its role in motor function recovery. METHODS: Electronic databases were searched by two independent assessors. Studies were included if they described interventions which examined the phenomenon of cross-education of strength from the less-affected to the more-affected side in stroke survivors. Study quality was assessed using the PEDro scale and the Cochrane risk of bias assessment tool. RESULTS: Only two controlled trials met the eligibility criteria. The results of both studies show a clear trend towards cross-educational strength transfer in post-stroke hemiplegic patients with 31.4% and 45.5% strength increase in the untrained, more-affected dorsiflexor muscle. Results also suggest a possible translation of strength gains towards functional task improvements and motor recovery. CONCLUSION: Based on best evidence synthesis guidelines the combination of the results included in this review suggest at least a moderate level of evidence for the application of cross education of strength in stroke rehabilitation. Following this review it is recommended that additional high quality randomized controlled trials are conducted to further support the findings. PMID- 26907194 TI - [Complex coronary intervention with overlapping of bioresorbable scaffolds. Case report and new insights review in the use of bioresorbable vascular scaffolds guided by optical coherence tomography]. AB - In recent years, the history of percutaneous coronary intervention has had a remarkable evolution. Currently, in Mexico are available the bioresorbable vascular scaffolds which have a very precise indications, and offer a new option in coronary intervention. We present the case and review of the published evidence, a new option for intervention with these devices, a complex case with 3 overlapping bioresorbable vascular scaffolds guided by optical coherence tomography. PMID- 26907195 TI - Aminocaproic acid for the management of bleeding in patients on extracorporeal membrane oxygenation: Four adult case reports and a review of the literature. AB - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is associated with a significant risk of bleeding and thrombosis. Despite high rates of bleeding and bleeding-related mortality in patients on ECMO, there is little evidence available to guide clinicians in the management of ECMO-associated bleeding. METHODS: We report the use of aminocaproic acid in four patients with bleeding on ECMO and a review of the literature. RESULTS: High D-dimer levels and low fibrinogen levels suggested that an antifibrinolytic agent may be effective as an adjunct to control bleeding. After aminocaproic acid administration, bleeding was controlled in each patient as evidenced by clinical and laboratory parameters. One patient suffered a cardiac arrest and care was withdrawn. CONCLUSIONS: In patients on ECMO with evidence of fibrinolysis, aminocaproic acid may be an effective option to control bleeding and to stabilize clot formation. PMID- 26907198 TI - Erratum. PMID- 26907196 TI - Preoperative maximal expiratory pressure is associated with duration of invasive mechanical ventilation after cardiac surgery: An observational study. AB - OBJECTIVE: To evaluate the association of maximal expiratory pressure (MEP), maximal inspiratory pressure (MIP), and peak expiratory flow (PEF) with total duration of invasive mechanical ventilation (IMV) in subjects undergoing cardiac surgery. BACKGROUND: Prolonged IMV is associated with respiratory infections, prolonged hospitalization, and increased mortality. Pulmonary function tests can help predict postoperative outcomes after cardiac surgery. METHODS: We recruited subjects admitted for cardiac surgery. All MIP, MEP, and PEF measurements were performed before surgery. Multivariable analysis was performed using a multiple linear regression model to control for possible confounders and test for association of MIP, MEP, and PEF with IMV duration. RESULTS: Overall, 125 subjects were included in the study. Higher MEP was associated with reduced duration of IMV after adjustment for confounders (P = 0.015), but no such association was observed between MIP or PEF and IMV. CONCLUSIONS: In subjects undergoing elective cardiac surgery, preoperative MEP is associated with IMV duration. PMID- 26907199 TI - Correlation of higher order aberrations in the anterior corneal surface and degree of keratoconus measured with a Scheimpflug camera. AB - OBJECTIVE: To determine the correlation of higher order aberrations in anterior corneal surface and degree of keratoconus measured with a Scheimpflug camera. MATERIAL AND METHODS: A descriptive, cross-sectional study was conducted on 152 eyes (both eyes of each patient) of patients with keratoconus, from January 2009 to April 2014. An examination was performed on the corneal aberrometry in the anterior corneal surface, and topographic mapping (by Amsler and Muckenhirn classification) was used to determine the degree of keratoconus. The correlation between high-order aberrations in anterior corneal surface and the degree of keratoconus was determined. RESULTS: Coma aberration significantly correlated with keratoconus severity (r=.60, P<.01), as well as with the high order aberration (r=.61, P<.01). Trefoil and keratoconus were weakly correlated (r=.34, P<.01). CONCLUSION: Higher order aberrations in anterior corneal surface were positively correlated with the degree of keratoconus in a similar way to the entire optical system. PMID- 26907200 TI - Substituent-dependent backward reaction in mechanofluorochromism of dibenzoylmethanatoboron difluoride derivatives. AB - The thermally backward reaction involved in the mechanofluorochromism of dibenzoylmethanatoboron difluoride (BF2DBM) derivatives, accompanied by an amorphous-crystalline phase transition, was quantitatively evaluated based on kinetics and thermodynamics. The kinetics was discussed by evaluation of the effect of temperature on the time-dependent changes of the fluorescence intensity for amorphous samples obtained by mechanical grinding. The thermodynamics was discussed based on data for the amorphous-crystalline phase transition obtained by differential scanning calorimetry. The enthalpy of activation (DeltaH(?)) of BF2DBM derivatives with MeO groups (2aBF2) was larger than that of derivatives with alkyl groups (2b-dBF2), whereas the entropy of activation (DeltaS(?)) was smaller than that of the derivatives with alkyl groups. It is proposed that the reaction dynamics of 2aBF2 will be governed by rotational motion around the C(methyl)-O bond. Interestingly, the Gibbs energies of activation (DeltaG(?)) were comparable for the reactions of all members of the BF2DBM series, though DeltaH(?) and DeltaS(?) were strongly dependent on the identity of the substituent. It is proposed that the substituent-dependent DeltaS(?) term is one of the key parameters for understanding the mechanofluorochromism of BF2DBM derivatives associated with the amorphous-crystalline phase transition. These findings will also provide important insights into the process of formation of crystal nuclei in moving from the melted to the crystalline state. PMID- 26907201 TI - Homology modeling of a Camelid antibody fragment against a conserved region of Acinetobacter baumannii biofilm associated protein (Bap). AB - BACKGROUND: VHH or the single-domain antibodies (sdAb), are studied for therapeutic applications in cancers, infections and other diseases. In our previous study, we expressed and produced a soluble VHH against a conserved region of Acinetobacter baumannii biofilm associated protein (Bap). The present study was undertaken to predict the 2D and 3D structure of the receptor and ligand as well as residues involved in their interactions. METHODS AND FINDINGS: Apart from ab initio, other rational methods such as homology modeling and threading were invoked to achieve the 3D structures. For homology modeling, BLAST was run on the sequences in order to find the best templates. Pocket detection and identification of functionally and structurally important residues of VHH 3D structure as well as determination of its clefts and ligand binding site were carried out on the structure. ZDOCK docking server predicted all possible binding modes in the translational and rotational space between the selected region of Bap as an antigen and the VHH structure as an antibody. CONCLUSION: We identified the amino acids involved in antigen-VHH interactions. Some functional conserved residues located in the largest cleft that participate in ligand binding site are identified. It seems that these amino acids are involved in antigen-VHH interactions. PMID- 26907202 TI - The institution as a blunt instrument: Cooperation through imperfect observability. AB - Observing others enables us to indirectly reciprocate their actions. In large societies, however, reliable individual observation is hard to achieve. Societies therefore rely on institutions to aid in observing cooperative behaviour and identifying those who cooperated. Institutions are integral part of modern societies. Here, we propose an evolutionary model in which an institution aims to label cooperators with a tag to verify their trustworthiness, as is the case for financial credit ratings or quality certificates. However, errors in assigning tags inevitably arise: the institution may accidentally leave some cooperators untagged or award tags to some defectors. Taking these two specific types of errors into account, we derive simple analytical conditions under which cooperation becomes stable and is favoured by selection. We find that these two institutional errors are not weighted equally in promoting cooperation: it is more detrimental to cooperation if tags are erroneously awarded to defectors than if they are mistakenly withheld from cooperators. Institutional tagging can lead to non-uniform interaction rates among cooperators and defectors, whereby cooperators benefit disproportionally by playing more games than defectors. This work sheds light on the significant role of institutions in promoting and maintaining societal cooperation. PMID- 26907203 TI - Cooperation, conformity, and the coevolutionary problem of trait associations. AB - In large scale social systems, coordinated or cooperative outcomes become difficult because encounters between kin or repeated encounters between friends are infrequent. Even punishment of noncooperators does not entirely alleviate the dilemma. One important mechanism for achieving cooperative outcomes in such social systems is conformist bias where individuals copy the behavior performed by the majority of their group mates. Conformist bias enhances group competition by both stabilizing behaviors within groups and increasing variance between groups. Due to this group competition effect, conformist bias is thought to have been an important driver of human social complexity and cultural diversity. However, conformist bias only evolves indirectly through associations with other traits, and I show that such associations are more difficult to obtain than previously expected. Specifically, I show that initial measures of population structure must be strong in order for a strong association between conformist bias and cooperative behaviors (cooperation and costly punishment) to evolve and for these traits to reach high frequencies. Additionally, the required initial level of association does not evolve de novo in simulations run over long timescales. This suggests that the coevolution of cooperative behaviors and conformist bias alone may not explain the high levels of cooperation within human groups, though conformist bias may still play an important role in combination with other social and demographic forces. PMID- 26907204 TI - Design and synthesis of a new generation of substituted purine hydroxamate analogs as histone deacetylase inhibitors. AB - Histone deacetylase inhibitors have been proved to be great potential for the treatment of cancer. Recently, we designed and modified a series of substituted purine hydroxamate analogs as potent HDAC inhibitors based on our previous studies. The target compounds were investigated for their in vitro HDAC inhibitory activities and anti-proliferative activities. Results indicated that these compounds could effectively inhibit HDAC and possess obvious anti proliferative activity against tumor cells. Promisingly, target compounds 4m and 4n outperformed SAHA in both enzymatic inhibitory activity and cellular anti proliferative activity assay. PMID- 26907205 TI - Reduction in E-cadherin expression fosters migration of Xenopus laevis primordial germ cells. AB - The transition from passive to active migration of primordial germ cells in Xenopus embryos correlates with a reduction in overall adhesion to surrounding endodermal cells as well as with reduced E-cadherin expression. Single cell force spectroscopy, in which cells are brought into brief contact with a gold surface functionalized with E-cadherin constructs, allows for a quantitative estimate of functional E-cadherin molecules on the cell surface. The adhesion force between migratory PGCs and the cadherin-coated surface was almost identical to cells where E-cadherin was knocked down by morpholino oligonucleotides (180 pN). In contrast, non-migratory PGCs display significantly higher adhesion forces (270 pN) on E-cadherin functionalised surfaces. On the basis of these observations, we propose that migration of PGCs in Xenopus embryos is regulated via modulation of E-cadherin expression levels, allowing these cells to move more freely if the level of E-cadherin is reduced. PMID- 26907206 TI - Nonalcoholic fatty liver disease and hepatocellular carcinoma. AB - The fastest growing cause of cancer-related death is hepatocellular carcinoma (HCC), which is at least partly attributable to the rising prevalence of non alcoholic fatty liver disease. Non-alcoholic fatty liver disease (NAFLD) encompasses a broad spectrum of conditions, ranging from non-progressive bland steatosis to malignant transformation into hepatocellular cancer. The estimated annual HCC incidence in the progressive form of NAFLD - non-alcoholic steatohepatitis (NASH) - is about 0.3%. The risk of HCC development is higher in men and increases with age, more advanced fibrosis, progressive obesity, insulin resistance and diabetes mellitus. Studies on the molecular mechanism of HCC development in NAFLD have shown that hepatocarcinogenesis is associated with complex changes at the immunometabolic interface. In line with these clinical risk factors, administration of a choline-deficient high-fat diet to mice over a prolonged period results in spontaneous HCC development in a high percentage of animals. The role of altered insulin signaling in tumorigenesis is further supported by the observation that components of the insulin-signaling cascade are frequently mutated in hepatocellular cancer cells. These changes further enhance insulin-mediated growth and cell division of hepatocytes. Furthermore, studies investigating nuclear factor kappa B (NF-kappaB) signaling and HCC development allowed dissection of the complex links between inflammation and carcinogenesis. To conclude, NAFLD reflects an important risk factor for HCC, develops also in non-cirrhotic livers and is a prototypic cancer involving inflammatory and metabolic pathways. STRENGTHS/WEAKNESSES AND SUMMARY OF THE TRANSLATIONAL POTENTIAL OF THE MESSAGES IN THE PAPER: The systematic review summarizes findings from unbiased clinical and translational studies on hepatocellular cancer in non alcoholic fatty liver disease. This provides a concise overview on the epidemiology, risk factors and molecular pathogenesis of the NAFL-NASH-HCC sequence. One limitation in the field is that few HCC studies stratify patients by underlying etiology, although the etiology of the underlying liver disease is an important co-determinant of clinical disease course and molecular pathogenesis. Molecular profiling of NAFL and associated HCC holds great translational potential for individualized surveillance, prevention and therapy. PMID- 26907207 TI - Letter to the Editor. PMID- 26907208 TI - Drug quality analysis through high performance liquid chromatography of isometamidium chloride hydrochloride and diminazene diaceturate purchased from official and unofficial sources in Northern Togo. AB - Trypanocidal drugs remain the most accessible and thus commonly used means of controlling tsetse transmitted animal African trypanosomosis. In Togo, trypanocides are sold on official as well as unofficial markets, but the quality of these trypanocides is undocumented so a drug quality assessment study was conducted from May 2013 to June 2014. Trypanocides supplied by European, Indian and Chinese pharmaceutical companies and sold on official and unofficial markets in Togo were purchased. In total fifty-two trypanocides were obtained, 24 of these samples from official markets and 28 from unofficial markets made up of a total of 36 diminazene diaceturate and 16 isometamidium chloride hydrochloride samples. The samples were analysed in the reference laboratory of the OIE (World Organisation for Animal Health), Laboratory for the Control of Veterinary Medicines (LACOMEV) in Dakar which uses galenic testing and high performance liquid chromatography (HPLC) testing as standard reference analysis methods. The results revealed a high proportion of trypanocides of sub-standard quality on the Togolese market: 40% were non-compliant to these quality reference standards. All of the HPLC non-compliant samples contained lower amounts of active ingredient compared to the concentration specified on the packaging. Non-compliance was higher in samples from the unofficial (53.57%) than from the official markets (25%; p=0.04).The main drug manufacturers, mostly of French origin in the study area, supply quality drugs through the official legal distribution circuit. Products of other origins mostly found on illegal markets present a significantly lower quality. PMID- 26907209 TI - Effects of exposure to Bovine viral diarrhoea virus 1 on risk of bovine respiratory disease in Australian feedlot cattle. AB - Viruses play a key role in the complex aetiology of bovine respiratory disease (BRD). Bovine viral diarrhoea virus 1 (BVDV-1) is widespread in Australia and has been shown to contribute to BRD occurrence. As part of a prospective longitudinal study on BRD, effects of exposure to BVDV-1 on risk of BRD in Australian feedlot cattle were investigated. A total of 35,160 animals were enrolled at induction (when animals were identified and characteristics recorded), held in feedlot pens with other cattle (cohorts) and monitored for occurrence of BRD over the first 50days following induction. Biological samples collected from all animals were tested to determine which animals were persistently infected (PI) with BVDV-1. Data obtained from the Australian National Livestock Identification System database were used to determine which groups of animals that were together at the farm of origin and at 28days prior to induction (and were enrolled in the study) contained a PI animal and hence to identify animals that had probably been exposed to a PI animal prior to induction. Multi-level Bayesian logistic regression models were fitted to estimate the effects of exposure to BVDV-1 on the risk of occurrence of BRD. Although only a total of 85 study animals (0.24%) were identified as being PI with BVDV-1, BVDV-1 was detected on quantitative polymerase chain reaction in 59% of cohorts. The PI animals were at moderately increased risk of BRD (OR 1.9; 95% credible interval 1.0-3.2). Exposure to BVDV-1 in the cohort was also associated with a moderately increased risk of BRD (OR 1.7; 95% credible interval 1.1-2.5) regardless of whether or not a PI animal was identified within the cohort. Additional analyses indicated that a single quantitative real-time PCR test is useful for distinguishing PI animals from transiently infected animals. The results of the study suggest that removal of PI animals and/or vaccination, both before feedlot entry, would reduce the impact of BVDV-1 on BRD risk in cattle in Australian feedlots. Economic assessment of these strategies under Australian conditions is required. PMID- 26907210 TI - Factors associated with usage of antimicrobials in commercial mink (Neovison vison) production in Denmark. AB - The American mink (Neovison vison) is used for commercial fur production in Denmark. In recent years, antimicrobial prescription for Danish mink has been increasing. In this study, the patterns and trends in antimicrobial use in mink were described and a multi-variable variance analysis was carried out with the objective of identifying risk factors for antimicrobial use on herd level. The study was based on register data for 2007-2012. Information on antimicrobial use was obtained from the national database VetStat, monitoring all medicinal products used for animals on prescription level. Data on microbiological feed quality was obtained from the Voluntary Feed Control under the Mink producers Organization, and data on herd size and the relation between farm and feed producer was obtained from the registers at Kopenhagen Fur, based on yearly reporting from the mink producers. Descriptive analysis showed a clear significant effect of season on antimicrobial use, with a peak in "treatment proportions", TP (defined daily doses per kg biomass-days) in May, around the time of whelping, and a high level in the following months. In autumn, a minor peak in antimicrobial use occurred throughout the study period. From 2007 to 2011, a 102% increase in annual antimicrobial TP was noted; on herd level, the increase was associated with an increasing frequency of prescription, and a decrease in the amounts prescribed in months with prescription. A binomial model showed that on herd level, the annual number of months with antimicrobial prescription was significantly (p<0.01) affected by feed producer, veterinarian, disease (specific laboratory diagnosis) infection, herd size and year, with an interaction between feed producer and year. A log-normal model showed that in months with antimicrobial use, the TP on herd level was significantly (p<0.001) affected by year, month (season), feed producer, feed quality score, veterinarian, herd size and laboratory confirmed diagnosis of specific infections; additionally the interaction terms year*feed producer and herd size*month were significant (p<0.001). In conclusion, antimicrobial use on herd level was significantly associated with the microbiological food quality, the feed producer, and the veterinarian. The prescription patterns varied significantly between veterinarians, and some veterinarians were associated with both larger and more frequent prescriptions of antimicrobials at herd level. Herd size is associated with different prescription patterns. Finally, infection with Pseudomonas aeruginosa, astrovirus, influenza virus and Salmonella spp. was associated with an increase in antimicrobial use. PMID- 26907211 TI - Metabolic prediction of important agronomic traits in hybrid rice (Oryza sativa L.). AB - Hybrid crops have contributed greatly to improvements in global food and fodder production over the past several decades. Nevertheless, the growing population and changing climate have produced food crises and energy shortages. Breeding new elite hybrid varieties is currently an urgent task, but present breeding procedures are time-consuming and labour-intensive. In this study, parental metabolic information was utilized to predict three polygenic traits in hybrid rice. A complete diallel cross population consisting of eighteen rice inbred lines was constructed, and the hybrids' plant height, heading date and grain yield per plant were predicted using 525 metabolites. Metabolic prediction models were built using the partial least square regression method, with predictive abilities ranging from 0.858 to 0.977 for the hybrid phenotypes, relative heterosis, and specific combining ability. Only slight changes in predictive ability were observed between hybrid populations, and nearly no changes were detected between reciprocal hybrids. The outcomes of prediction of the three highly polygenic traits demonstrated that metabolic prediction was an accurate (high predictive abilities) and efficient (unaffected by population genetic structures) strategy for screening promising superior hybrid rice. Exploitation of this pre-hybridization strategy may contribute to rice production improvement and accelerate breeding programs. PMID- 26907212 TI - Autoantigens as Partners in Initiation and Propagation of Autoimmune Rheumatic Diseases. AB - Systemic autoimmune diseases are characterized by specific targeting of a limited group of ubiquitously expressed autoantigens by the immune system. This review examines the mechanisms underlying their selection as immune targets. Initiation of autoimmune responses likely reflects the presentation of antigens with a distinct structure not previously encountered by the immune system, in a proimmune context (injury, malignancy, or infection). Causes of modified structure include somatic mutation and posttranslational modifications (including citrullination and proteolysis). Many autoantigens are components of multimolecular complexes, and some of the other components may provide adjuvant activity. Propagation of autoimmune responses appears to reflect a bidirectional interaction between the immune response and the target tissues in a mutually reinforcing cycle: Immune effector pathways generate additional autoantigen, which feeds further immune response. We propose that this resonance may be a critical principle underlying disease propagation, with specific autoantigens functioning as the hubs around which amplification occurs. PMID- 26907213 TI - Neuroimmunity: Physiology and Pathology. AB - Evolution has yielded multiple complex and complementary mechanisms to detect environmental danger and protect tissues from damage. The nervous system rapidly processes information and coordinates complex defense behaviors, and the immune system eliminates diverse threats by virtue of mobile, specialized cell populations. The two systems are tightly integrated, cooperating in local and systemic reflexes that restore homeostasis in response to tissue injury and infection. They further share a broad common language of cytokines, growth factors, and neuropeptides that enables bidirectional communication. However, this reciprocal cross talk permits amplification of maladaptive feedforward inflammatory loops that contribute to the development of allergy, autoimmunity, itch, and pain. Appreciating the immune and nervous systems as a holistic, coordinated defense system provides both new insights into inflammation and exciting opportunities for managing acute and chronic inflammatory diseases. PMID- 26907214 TI - Variations in MHC Class II Antigen Processing and Presentation in Health and Disease. AB - MHC class II (MHC-II) molecules are critical in the control of many immune responses. They are also involved in most autoimmune diseases and other pathologies. Here, we describe the biology of MHC-II and MHC-II variations that affect immune responses. We discuss the classic cell biology of MHC-II and various perturbations. Proteolysis is a major process in the biology of MHC-II, and we describe the various components forming and controlling this endosomal proteolytic machinery. This process ultimately determines the MHC-II-presented peptidome, including cryptic peptides, modified peptides, and other peptides that are relevant in autoimmune responses. MHC-II also variable in expression, glycosylation, and turnover. We illustrate that MHC-II is variable not only in amino acids (polymorphic) but also in its biology, with consequences for both health and disease. PMID- 26907215 TI - Follicular Helper T Cells. AB - Although T cell help for B cells was described several decades ago, it was the identification of CXCR5 expression by B follicular helper T (Tfh) cells and the subsequent discovery of their dependence on BCL6 that led to the recognition of Tfh cells as an independent helper subset and accelerated the pace of discovery. More than 20 transcription factors, together with RNA-binding proteins and microRNAs, control the expression of chemotactic receptors and molecules important for the function and homeostasis of Tfh cells. Tfh cells prime B cells to initiate extrafollicular and germinal center antibody responses and are crucial for affinity maturation and maintenance of humoral memory. In addition to the roles that Tfh cells have in antimicrobial defense, in cancer, and as HIV reservoirs, regulation of these cells is critical to prevent autoimmunity. The realization that follicular T cells are heterogeneous, comprising helper and regulatory subsets, has raised questions regarding a possible division of labor in germinal center B cell selection and elimination. PMID- 26907216 TI - Chemokines and Chemokine Receptors in Lymphoid Tissue Dynamics. AB - The continuous migration of immune cells between lymphoid and nonlymphoid organs is a key feature of the immune system, facilitating the distribution of effector cells within nearly all compartments of the body. Furthermore, reaching their correct position within primary, secondary, or tertiary lymphoid organs is a prerequisite to ensure immune cells' unimpaired differentiation, maturation, and selection, as well as their activation or functional silencing. The superfamilies of chemokines and chemokine receptors are of major importance in guiding immune cells to and within lymphoid and nonlymphoid tissues. In this review we focus on the role of the chemokine system in the migration dynamics of immune cells within lymphoid organs at the steady state and on how these dynamics are affected by infectious and inflammatory processes. PMID- 26907217 TI - Galectins and Immune Responses-Just How Do They Do Those Things They Do? AB - Galectins are a family of mammalian carbohydrate-binding proteins expressed by many cell types. Galectins can function intracellularly and can also be secreted to bind to cell surface glycoconjugate counterreceptors. Some galectins are made by immune cells, whereas other galectins are secreted by different cell types, such as endothelial or epithelial cells, and bind to immune cells to regulate immune responses. Galectin binding to a single glycan ligand is a low-affinity interaction, but the multivalency of galectins and the glycan ligands presented on cell surface glycoproteins results in high-avidity binding that can reversibly scaffold or cluster these glycoproteins. Galectin binding to a specific glycoprotein counterreceptor is regulated in part by the repertoire of glycosyltransferase enzymes (which make the glycan ligands) expressed by that cell, and the effect of galectin binding results from clustering or retention of specific glycoprotein counterreceptors bearing these specific ligands. PMID- 26907219 TI - Defining a diagnostic gene signature for tuberculosis. PMID- 26907218 TI - Genome-wide expression for diagnosis of pulmonary tuberculosis: a multicohort analysis. AB - BACKGROUND: Active pulmonary tuberculosis is difficult to diagnose and treatment response is difficult to effectively monitor. A WHO consensus statement has called for new non-sputum diagnostics. The aim of this study was to use an integrated multicohort analysis of samples from publically available datasets to derive a diagnostic gene set in the peripheral blood of patients with active tuberculosis. METHODS: We searched two public gene expression microarray repositories and retained datasets that examined clinical cohorts of active pulmonary tuberculosis infection in whole blood. We compared gene expression in patients with either latent tuberculosis or other diseases versus patients with active tuberculosis using our validated multicohort analysis framework. Three datasets were used as discovery datasets and meta-analytical methods were used to assess gene effects in these cohorts. We then validated the diagnostic capacity of the three gene set in the remaining 11 datasets. FINDINGS: A total of 14 datasets containing 2572 samples from 10 countries from both adult and paediatric patients were included in the analysis. Of these, three datasets (N=1023) were used to discover a set of three genes (GBP5, DUSP3, and KLF2) that are highly diagnostic for active tuberculosis. We validated the diagnostic power of the three gene set to separate active tuberculosis from healthy controls (global area under the ROC curve (AUC) 0.90 [95% CI 0.85-0.95]), latent tuberculosis (0.88 [0.84-0.92]), and other diseases (0.84 [0.80-0.95]) in eight independent datasets composed of both children and adults from ten countries. Expression of the three gene set was not confounded by HIV infection status, bacterial drug resistance, or BCG vaccination. Furthermore, in four additional cohorts, we showed that the tuberculosis score declined during treatment of patients with active tuberculosis. INTERPRETATION: Overall, our integrated multicohort analysis yielded a three-gene set in whole blood that is robustly diagnostic for active tuberculosis, that was validated in multiple independent cohorts, and that has potential clinical application for diagnosis and monitoring treatment response. Prospective laboratory validation will be required before it can be used in a clinical setting. FUNDING: National Institute of Allergy and Infectious Diseases, National Library of Medicine, the Stanford Child Health Research Institute, the Society for University Surgeons, and the Bill and Melinda Gates Foundation. PMID- 26907220 TI - Clinical implications of antibiotic impact on gastrointestinal microbiota and Clostridium difficile infection. AB - The human gastrointestinal (GI) microbiota plays an important role in human health. Anaerobic bacteria prevalent in the normal colon suppress the growth of non-commensal microorganisms, thus maintaining colonic homeostasis. The GI microbiota is influenced by both patient-specific and environmental factors, particularly antibiotics. Antibiotics can alter the native GI microbiota composition, leading to decreased colonization resistance and opportunistic proliferation of non-native organisms. A common and potentially serious antibiotic-induced sequela associated with GI microbiota imbalance is Clostridium difficile infection (CDI), which may become recurrent if dysbiosis persists. This review focuses on the association between antibiotics and CDI, and the antibiotic induced disruption leading to recurrent CDI. Promoting antibiotic stewardship is pivotal in protecting native microbiota and reducing the incidence of CDI and other GI infections. PMID- 26907221 TI - Drainless mastectomy: Is it safe and effective? AB - : Practice regarding the use of post operative drains after simple mastectomy varies widely. This project aimed to establish if not using a drain lead to an increase in post-operative seroma formation or other complications. METHODS: Women undergoing simple mastectomy +/- sentinel node biopsy were included. Patients were allocated to drain/no drain group via operating surgeon. Data was collected retrospectively from computer based records. Drain output, length of stay, seroma formation and volume and post-operative complications were recorded. RESULTS: There were 39 patients in the drain group and 24 patients in the no drain group. Patients did not differ significantly in terms of age, BMI or specimen weight. Seroma was more prevalent in the no drain group (62 v 83%) and required more clinic attendances for aspiration with larger volumes drained (360 vs 725 ml, p = 0.0096). There was no difference in overall complication rate. There did not appear to be a correlation between seroma formation and age, BMI or mastectomy weight. CONCLUSIONS: The use of a drain after simple mastectomy may confer lower rates of seroma formation as well as lower overall volumes. Therefore drainless mastectomy appears to be safe but may require more post operative intervention. PMID- 26907222 TI - Negative-dominance phenomenon with genetic variants of the cardiac sodium channel Nav1.5. AB - During the past two decades, many pathological genetic variants in SCN5A, the gene encoding the pore-forming subunit of the cardiac (monomeric) sodium channel Na(v)1.5, have been described. Negative dominance is a classical genetic concept involving a "poison" mutant peptide that negatively interferes with the co expressed wild-type protein, thus reducing its cellular function. This phenomenon has been described for genetic variants of multimeric K(+) channels, which mechanisms are well understood. Unexpectedly, several pathologic SCN5A variants that are linked to Brugada syndrome also demonstrate such a dominant-negative (DN) effect. The molecular determinants of these observations, however, are not yet elucidated. This review article summarizes recent findings that describe the mechanisms underlying the DN phenomenon of genetic variants of K(+), Ca(2+), Cl( ) and Na(+) channels, and in particular Brugada syndrome variants of Na(v)1.5. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel. PMID- 26907223 TI - Novel Inhibitors for a Novel Binding Site in Respiratory Complex III. AB - A new binding site and potential novel inhibitors of the respiratory complex III are described. The site is located at the opposite side of the enzyme with respect to ubiquinol binding site (Qo site), and distinctly different from both Qo and Qi sites (hence designated as Non-Q binding site, NQ). NQ site binding pocket extends up close to Phe90 residue, an internal switch (LH switch) that regulates electron transfer between heme bL and heme bH of the low potential redox chain. Docking studies and molecular dynamics simulations of different molecules to the NQ site revealed potential ligands which exhibit a novel inhibitory effect for bc1 complex by switching the LH switch to "off" conformation, thereby shutting down electron transfer in the low potential redox chain. Moreover, the novel inhibitors have lower binding affinity for both Qo and Qi sites, and hence do not interfere with binding of the natural ligands to those sites. The inhibitory activity of those novel ligands in bc1 complex is suggested to promote the production of reactive oxygen species (ROS) at the Qo site. Hence those ligands are potential candidates for designing new "mitocan" drugs. PMID- 26907224 TI - 3D Surgical Printing Cutting Guides for Open-Wedge High Tibial Osteotomy: Do It Yourself. AB - Opening wedge osteotomy has recently gained popularity, thanks to the recent implementation of locking plates, which have shown equivalent stability with greater reproducibility, accuracy, and longevity than the closing wedge techniques and a lower prosthetic conversion rate. We present a new "do-it yourself" cutting guides system for tibial opening osteotomy. Using a conventional computed tomography digital image, a positioning guide and wedge spacers were printed in three dimensions (3D) for implementing the osteotomy and obtaining the planned correction. The surgeon makes the whole process in a do-it yourself style. This new technique was used in eight cases. Previous opening osteotomies with the standard technique were used as control (20 cases). Surgical time, fluoroscopic time, and accuracy of the axial correction were measured. The use of a custom positioning guide reduced the surgical (31 minutes less) and fluoroscopic times (6.9 times less) while achieving a high-axis correction accuracy compared with the standard technique. Digitally planned and executed osteotomies under 3D printed osteotomy positioning guides help the surgeon to minimize human error while reducing surgical time. The reproducibility of this technique is very robust, allowing a transfer of the steps planned in a virtual environment to the operating table. PMID- 26907225 TI - Influence of Posterior Cruciate Ligament Tension on Knee Kinematics and Kinetics. AB - The posterior cruciate ligament (PCL) has an important role in cruciate-retaining total knee arthroplasty to achieve good clinical results. The purpose of the study was to examine the influence of PCL tension on knee kinematics and kinetics and to propose an indicator for proper PCL tension during surgery. A squatting activity was simulated in a weight-bearing deep knee bend using a musculoskeletal computer simulation knee model. The length of the PCL was changed to represent different PCL tension models. The amount of PCL tension significantly influenced knee kinematics and kinetics. In the normal PCL model, the facet center positions at 90 degrees of knee flexion were positioned at almost the same position as in full extension. A loose PCL-induced paradoxical anterior movement and greater patellofemoral forces, whereas a tight PCL was related to excessive rollback and increased tibiofemoral forces. This study suggested ideal knee kinematics with proper PCL tension, in which the medial contact position at full flexion was almost similar to the position at 90 degrees of knee flexion. PMID- 26907226 TI - Risk Factors Comparison for Radial and Horizontal Tears. AB - Tears in posterior horn of medial meniscus mainly included horizontal tear, transversal tear, radial tear, complex tear, and bucket handle tear. We analyzed and compared the risk factors for radial tear and horizontal tear in the posterior horn of medial meniscus. A total of 407 consecutive cases who received arthroscopic treatment of medial meniscus tears were analyzed retrospectively. Among them, 103 cases were radial tear in posterior horn of medial meniscus and 107 were horizontal tear. Clinical data records included patients' age, gender, duration of symptoms, body mass index, trauma history, and slope angle of tibia, valgus angle of knee, and grading of cartilage (Outerbridge Grades) were collected and analyzed. In addition, multiple-factor nonconditional logistic regression was adopted to analyze the related risk factors in these two types of medial meniscus tears. The two groups have no difference in age, trauma history, slope angle of tibia, and duration of symptoms but have significant difference in gender, body mass index, and valgus angle of knee and grading of cartilage. Multiple factors analysis indicated that valgus angle, age, and grading of cartilage were risk factors in medial meniscus tears. Patients with posterior horn tear in medial meniscus have higher incidence among senile osteoarthritis, while radial tear was more likely to occur in elderly patients with knee-joint varus and serious cartilage degeneration. PMID- 26907227 TI - Authors' Response. PMID- 26907228 TI - More about low-dose rituximab and plasma exchange as front-line therapy for patients with thrombotic thrombocytopenic purpura. AB - INTRODUCTION: Thrombotic thrombocytopenic purpura (TTP) is characterized by a reduction in the von Willebrand cleavage protein ADAMTS-13, mainly as a consequence of autoimmunity. Plasma exchange (PEx) is standard, achieving complete remission (CR) in 77-83% of cases, but rates are variable depending on ADAMTS-13 activity and relapse is frequent in patients with <10%. Thus, an effective front-line immunosuppressive treatment is needed. MATERIALS AND METHODS: We administered PEx daily until CR and rituximab 100 mg/dose/week for 4 consecutive weeks to 10 patients with a first TTP episode and 1 relapsed patient (8 females (72%) and 3 males (28%)). Median age was 34 years (15-46) and laboratory parameters at diagnosis were as follows: platelets 11 * 10(9)/l (range 7-27.4 * 10(9)/l), lactate dehydrogenase 1822 U/l (range 705-8220 U/l, normal 70 180 U/l), and haemoglobin 6 g/dl (range 4.2-11.8 g/dl). ADAMTS-13 activity was determined in eight patients and was <10% in all. ADAMTS-13 autoantibody titre was determined in seven patients and was >15 units/ml in all (ref: negative <12, undetermined 12-15, positive >15 units/ml); Shiga toxin was negative in all patients. The median number of PEx until CR was 7 (range 4-12); prednisone 1 mg/kg was administered to six patients. RESULTS: The median follow-up was 22 months (range 4-49) and the estimated 2-year relapse-free survival was 89%; one HIV+ patient relapsed at 8 months follow-up. No complications related to PEx or rituximab were reported. CONCLUSIONS: Our study suggests that low-dose rituximab and PEx are effective as front-line treatment for acute TTP; however, a prospective trial is needed to demonstrate whether low-dose rituximab is as effective as the conventional dose. PMID- 26907229 TI - Molecular impacts of perfluorinated chemicals (PFASs) in the liver and testis of male largemouth bass (Micropterus salmoides) in Minnesota Lakes. AB - Perfluorinated chemicals (PFASs) stem from a wide range of sources and have been detected in aquatic ecosystems worldwide, including the upper Midwest and the state of Minnesota in the USA. This study investigated whether fish with high body burden levels of PFASs in the Twin Cities Metro Areas showed any evidence of adverse effects at the level of the transcriptome. We hypothesized that fish with higher body burden levels of PFASs would exhibit molecular responses in the liver and testis that were suggestive of oxidative and general stress, as well as impaired reproduction. Concentrations of PFASs in largemouth bass varied significantly across the sampled lakes, with the lowest concentrations of PFASs found in fish from Steiger and Upper Prior Lakes and the highest concentrations found in fish from Calhoun and Twin Lakes. Largemouth bass with high PFAS concentrations exhibited changes in the expression of genes related to lipid metabolism, energy production, RNA processing, protein production/degradation and contaminant detoxification, all of which are consistent with biomarker responses observed in other studies with PFASs. However, given the wide range of genes that were differentially expressed across the lakes and the variability observed in the mechanisms through which biological processes were affected, it is unlikely that PFASs are the only stressors affecting largemouth bass in the Twin Cities Metro Areas lakes. Indeed, Twin Lake is affected by the Joslyn superfund site which contains polycyclic aromatic hydrocarbons, pentachlorophenol, polychlorinated biphenyls, and dioxins. These compounds are also expected to drive the transcriptomics responses observed, but to what degree is difficult to ascertain at this time. PMID- 26907230 TI - The Diels-Alder Cycloaddition Reaction of Substituted Hemifullerenes with 1,3 Butadiene: Effect of Electron-Donating and Electron-Withdrawing Substituents. AB - The Diels-Alder (DA) reaction provides an attractive route to increase the number of six member rings in substituted Polycyclic Aromatic Hydrocarbons (PAHs). The density functional theory (DFT) B3LYP method has been used in this work to inquire if the substitution of H over the edge of triindenetriphenylene (pristine hemifullerene 1) and pentacyclopentacorannulene (pristine hemifullerene 2), could improve the DA cycloaddition reaction with 1,3-butadiene. The substituents tested include electron-donating (NH2, OMe, OH, Me, i-Pr) and electron-withdrawing groups (F, COOH, CF3, CHO, CN, NO2). The electronic, kinetic and thermodynamic parameters of the DA reactions of the substituted hemifullerenes with 1,3 butadiene have been analyzed. The most promising results were obtained for the NO2 substituent; the activation energy barriers for reactions using this substituent were lower than the barriers for the pristine hemifullerenes. This leads us to expect that the cycloadditions to a starting fullerene fragment will be possible. PMID- 26907231 TI - Molecular Theory of Detonation Initiation: Insight from First Principles Modeling of the Decomposition Mechanisms of Organic Nitro Energetic Materials. AB - This review presents a concept, which assumes that thermal decomposition processes play a major role in defining the sensitivity of organic energetic materials to detonation initiation. As a science and engineering community we are still far away from having a comprehensive molecular detonation initiation theory in a widely agreed upon form. However, recent advances in experimental and theoretical methods allow for a constructive and rigorous approach to design and test the theory or at least some of its fundamental building blocks. In this review, we analyzed a set of select experimental and theoretical articles, which were augmented by our own first principles modeling and simulations, to reveal new trends in energetic materials and to refine known existing correlations between their structures, properties, and functions. Our consideration is intentionally limited to the processes of thermally stimulated chemical reactions at the earliest stage of decomposition of molecules and materials containing defects. PMID- 26907232 TI - Antifungal Activity of Isoliquiritin and Its Inhibitory Effect against Peronophythora litchi Chen through a Membrane Damage Mechanism. AB - This study investigated the antifungal activity and potential antifungal mechanism(s) of isoliquiritin against P. litchi Chen, one of the main litchi pathogens. The antifungal activity of isoliquiritin against P. litchi Chen had been proven in a dose-dependent manner through in vitro (mycelial growth and sporangia germination) and in vivo (detached leaf) tests. Results revealed that isoliquiritin exhibited significant antifungal activity against the tested pathogens, especially, P. litchi Chen, with a minimum inhibitory concentration of 27.33 mg/L. The morphology of P. litchi Chen was apparently changed by isoliquiritin through cytoplasm leakage and distortion of mycelia. The cell membrane permeability of the P. litchi Chen increased with the increasing concentration of isoliquiritin, as evidenced by a rise in relative electric conductivity and a decrease in reducing sugar contents. These results indicated that the antifungal effects of isoliquiritin could be explained by a membrane lesion mechanism causing damage to the cell membrane integrity leading to the death of mycelial cells. Taken together, isoliquiritin may be used as a natural alternative to commercial fungicides or a lead compound to develop new fungicides for the control of litchi downy blight. PMID- 26907233 TI - Characterizing the Solvated Structure of Photoexcited [Os(terpy)2](2+) with X-ray Transient Absorption Spectroscopy and DFT Calculations. AB - Characterizing the geometric and electronic structures of individual photoexcited dye molecules in solution is an important step towards understanding the interfacial properties of photo-active electrodes. The broad family of "red sensitizers" based on osmium(II) polypyridyl compounds often undergoes small photo-induced structural changes which are challenging to characterize. In this work, X-ray transient absorption spectroscopy with picosecond temporal resolution is employed to determine the geometric and electronic structures of the photoexcited triplet state of [Os(terpy)2](2+) (terpy: 2,2':6',2"-terpyridine) solvated in methanol. From the EXAFS analysis, the structural changes can be characterized by a slight overall expansion of the first coordination shell [OsN6]. DFT calculations supports the XTA results. They also provide additional information about the nature of the molecular orbitals that contribute to the optical spectrum (with TD-DFT) and the near-edge region of the X-ray spectra. PMID- 26907234 TI - Synthesis of 2-Alkenyl-2H-indazoles from 2-(2-Carbonylmethyl)-2H-indazoles. AB - A procedure has been developed for synthesis of 2-alkenyl-2H-indazoles starting from 2-(2-carbonylmethyl)-2H-indazoles, which are prepared by gallium/aluminium- and aluminium-mediated, direct, regioselective alkylation of indazoles with alpha bromocarbonyl compounds. The structure of 3-(2H-indazol-2-yl)-2H-chromen-2-one was proven by X-ray crystallography. The styrene- and coumarin-2H-indazoles produced by using the new method were found to have interesting fluorescence properties. PMID- 26907235 TI - Discovery of a New Class of Sortase A Transpeptidase Inhibitors to Tackle Gram Positive Pathogens: 2-(2-Phenylhydrazinylidene)alkanoic Acids and Related Derivatives. AB - A FRET-based random screening assay was used to generate hit compounds as sortase A inhibitors that allowed us to identify ethyl 3-oxo-2-(2 phenylhydrazinylidene)butanoate as an example of a new class of sortase A inhibitors. Other analogues were generated by changing the ethoxycarbonyl function for a carboxy, cyano or amide group, or introducing substituents in the phenyl ring of the ester and acid derivatives. The most active derivative found was 3-oxo-2-(2-(3,4dichlorophenyl)hydrazinylidene)butanoic acid (2b), showing an IC50 value of 50 uM. For a preliminary assessment of their antivirulence properties the new derivatives were tested for their antibiofilm activity. The most active compound resulted 2a, which showed inhibition of about 60% against S. aureus ATCC 29213, S. aureus ATCC 25923, S. aureus ATCC 6538 and S. epidermidis RP62A at a screening concentration of 100 uM. PMID- 26907236 TI - Porphyrin Cobalt(III) "Nitrene Radical" Reactivity; Hydrogen Atom Transfer from Ortho-YH Substituents to the Nitrene Moiety of Cobalt-Bound Aryl Nitrene Intermediates (Y = O, NH). AB - In the field of cobalt(II) porphyrin-catalyzed metallo-radical reactions, organic azides have emerged as successful nitrene transfer reagents. In the pursuit of employing ortho-YH substituted (Y = O, NH) aryl azides in Co(II) porphyrin catalyzed nitrene transfer reactions, unexpected hydrogen atom transfer (HAT) from the OH or NH2 group in the ortho-position to the nitrene moiety of the key radical-intermediate was observed. This leads to formation of reactive ortho iminoquinonoid (Y = O) and phenylene diimine (Y = NH) species. These intermediates convert to subsequent products in non-catalyzed reactions, as is typical for these free organic compounds. As such, the observed reactions prevent the anticipated cobalt-mediated catalytic radical-type coupling of the nitrene radical intermediates to alkynes or alkenes. Nonetheless, the observed reactions provide valuable insights into the reactivity of transition metal nitrene-radical intermediates, and give access to ortho-iminoquinonoid and phenylene diimine intermediates from ortho-YH substituted aryl azides in a catalytic manner. The latter can be employed as intermediates in one-pot catalytic transformations. From the ortho-hydroxy aryl azide substrates both phenoxizinones and benzoxazines could be synthesized in high yields. From the ortho-amino aryl azide substrates azabenzene compounds were obtained as the main products. Computational studies support these observations, and reveal that HAT from the neighboring OH and NH2 moiety to the nitrene radical moiety has a low energy barrier. PMID- 26907237 TI - The Impact of Melatonin in Research. AB - Citation indexes represent helpful tools for evaluating the impact of articles on research. The aim of this study was to obtain the top-100 ranking of the most cited papers on melatonin, a relevant neurohormone mainly involved in phase adjusting the biological clock and with certain sleep-promoting capability. An article search was carried out on the Institute for Scientific Information (ISI) Web of Science platform. Numbers of citations, names of authors, journals and their 2014-impact factor, year of publication, and experimental designs of studies were recorded. The ranking of the 100-most cited articles on melatonin research (up to February 2016) revealed a citation range from 1623 to 310. Narrative reviews/expert opinions were the most frequently cited articles, while the main research topics were oxidative stress, sleep physiology, reproduction, circadian rhythms and melatonin receptors. This study represents the first detailed analysis of the 100 top-cited articles published in the field of melatonin research, showing its impact and relevance in the biomedical field. PMID- 26907238 TI - Catechin Hydrate Augments the Antibacterial Action of Selected Antibiotics against Staphylococcus aureus Clinical Strains. AB - Synergistic effects between commonly used antibiotics and natural substances may be an alternative to conventional antibacterial therapies. The objective of the presented study was to assess the in vitro antibacterial activity of catechin hydrate (CH) and evaluate the interactions of CH with selected antibiotics using Staphylococcus aureus clinical and reference strains. CH displayed diverse activity towards examined S. aureus strains, with minimal inhibitory concentrations (MICs) ranging from 256 to 2048 ug/mL. The interaction between CH and antibiotics was assessed by an E-test. The most significant synergistic effects were noticed for CH in combination with clindamycin and erythromycin. For cefoxitin and vancomycin a decrease of MIC values in the presence of CH was also observed, but it did not reach statistical significance. The obtained results demonstrate that CH shows antimicrobial activity against Staphylococcus aureus clinical strains. What is more, we proved a synergistic effect of CH with erythromycin and clindamycin. PMID- 26907239 TI - Leccinum molle (Bon) Bon and Leccinum vulpinum Watling: The First Study of Their Nutritional and Antioxidant Potential. AB - This work presents the chemical profile of two edible species of mushrooms from the genus Leccinum: Leccinum molle (Bon) Bon and Leccinum vulpinum Watling, both harvested on the outskirts of Braganca (Northeastern Portugal). Both species were prepared and characterized regarding their content in nutrients (i.e., free sugars, fatty acids and vitamins), non-nutrients (i.e., phenolic and other organic acids) and antioxidant activity. To the best of our knowledge, no previous studies on the chemical characterization and bioactivity of these species have been undertaken. Accordingly, this study intends to increase the available information concerning edible mushroom species, as well as to highlight another important factor regarding the conservation of the mycological resources- their potential as sources of nutraceutical/pharmaceutical compounds. Overall, both species revealed similar nutrient profiles, with low fat levels, fructose, mannitol and trehalose as the foremost free sugars, and high percentages of mono- and polyunsaturated fatty acids. They also revealed the presence of bioactive compounds, namely phenolic (e.g., gallic acid, protocatechuic acid and p hydroxybenzoic acid) and organic acids (e.g., citric and fumaric acids) and presented antioxidant properties. PMID- 26907240 TI - Chemistry and Pharmacology of Citrus sinensis. AB - Presently the search for new drugs from natural resources is of growing interest to the pharmaceutical industry. Natural products have been the source of new drugs since ancient times. Plants are a good source of secondary metabolites which have been found to have beneficial properties. The present study is a review of the chemistry and pharmacology of Citrus sinensis. This review reveals the therapeutic potential of C. sinensis as a source of natural compounds with important activities that are beneficial for human health that could be used to develop new drugs. PMID- 26907241 TI - Synthesis of Oxylipin Mimics and Their Antifungal Activity against the Citrus Postharvest Pathogens. AB - Nine oxylipin mimics were designed and synthesized starting from d-mannose. Their antifungal activity against three citrus postharvest pathogens was evaluated by spore germination assay. The results indicated that all the compounds significantly inhibited the growth of Penicillium digitatum, Penicillium italicum and Aspergillus niger. The compound (3Z,6Z,8S,9R,10R)-octadeca-3,6-diene-8,9,10 triol (3) exhibited excellent inhibitory effect on both Penicillium digitatum (IC50 = 34 ppm) and Penicillium italicum (IC50 = 94 ppm). Their in vivo antifungal activities against citrus postharvest blue mold were tested with fruit inoculated with the pathogen Penicillium italicum. The compound (3R,4S)-methyl 3,4-dihydroxy-5-octyltetrahydrofuran-2-carboxylate (9) demonstrated significant efficacy by reducing the disease severity to 60%. The antifungal mechanism of these oxylipin mimics was postulated in which both inhibition of pathogenic mycelium and stimuli of the host oxylipin-mediated defense response played important roles. PMID- 26907242 TI - Multicomponent Synthesis and Evaluation of New 1,2,3-Triazole Derivatives of Dihydropyrimidinones as Acidic Corrosion Inhibitors for Steel. AB - An efficient one-pot synthesis of 1,2,3-triazole derivatives of dihydropyrimidinones has been developed using two multicomponent reactions. The aldehyde-1,2,3-triazoles were obtained in good yields from in situ-generated organic azides and O-propargylbenzaldehyde. The target heterocycles were synthesized through the Biginelli reaction in which the aldehyde-1,2,3-triazoles reacted with ethyl acetoacetate and urea in the presence of Ce(OTf)3 as the catalyst. The corrosion inhibition of steel grade API 5 L X52 in 1 M HCl by the synthesized compounds was investigated using the electrochemical impedance spectroscopy technique. The measurements revealed that these heterocycles are promising candidates to inhibit acidic corrosion of steel. PMID- 26907243 TI - Phenolics from Garcinia mangostana Inhibit Advanced Glycation Endproducts Formation: Effect on Amadori Products, Cross-Linked Structures and Protein Thiols. AB - Accumulation of Advanced Glycation Endproducts (AGEs) in body tissues plays a major role in the development of diabetic complications. Here, the inhibitory effect of bioactive metabolites isolated from fruit hulls of Garcinia mangostana on AGE formation was investigated through bio-guided approach using aminoguanidine (AG) as a positive control. Including G. mangostana total methanol extract (GMT) in the reaction mixture of bovine serum albumin (BSA) and glucose or ribose inhibited the fluorescent and non-fluorescent AGEs formation in a dose dependent manner. The bioassay guided fractionation of GMT revealed isolation of four bioactive constituents from the bioactive fraction; which were identified as: garcimangosone D (1), aromadendrin-8-C-glucopyranoside (2), epicatechin (3), and 2,3',4,5',6-pentahydroxybenzophenone (4). All the tested compounds significantly inhibited fluorescent and non-fluorescent AGEs formation in a dose dependent manner whereas compound 3 (epicatechin) was found to be the most potent. In search for the level of action, addition of GMT, and compounds 2-4 inhibited fructosamine (Amadori product) and protein aggregation formation in both glucose and ribose. To explore the mechanism of action, it was found that addition of GMT and only compound (3) to reaction mixture increased protein thiol in both glucose and ribose while compounds 1, 2 and 4 only increased thiol in case of ribose. In conclusion, phenolic compounds 1-4 inhibited AGEs formation at the levels of Amadori product and protein aggregation formation through saving protein thiol. PMID- 26907244 TI - Synthesis and Characterization of Some New Coumarins with in Vitro Antitumor and Antioxidant Activity and High Protective Effects against DNA Damage. AB - Coumarins are naturally occurring oxygen heterocyclic compounds having multifarious medicinal properties, hence used as lead compounds for designing new potent analogs. The chromene butenoic acid 3 and the benzochromene butenoic acid 4 which are derived from the reaction of glyoxalic acid with 3-acetylcoumarin and 3-acetylbenzocoumarin, respectively, were reacted with different nitrogen and carbon nucleophiles to give new heterocyclic compounds. The structures of the prepared compounds were elucidated by IR, 1H-NMR, and mass spectroscopy. Some of the newly prepared compounds were tested in vitro against a panel of four human tumor cell lines namely; hepatocellular carcinoma (liver) HepG2, colon cancer HCT 116, human prostate cancer PC3, and mammary gland breast MCF-7. Also they were tested as antioxidants. Almost all of the tested compounds showed satisfactory activity. PMID- 26907245 TI - Transcriptome Sequencing and Development of Genic SSR Markers of an Endangered Chinese Endemic Genus Dipteronia Oliver (Aceraceae). AB - Dipteronia Oliver (Aceraceae) is an endangered Chinese endemic genus consisting of two living species, Dipteronia sinensis and Dipteronia dyeriana. However, studies on the population genetics and evolutionary analyses of Dipteronia have been hindered by limited genomic resources and genetic markers. Here, the generation, de novo assembly and annotation of transcriptome datasets, and a large set of microsatellite or simple sequence repeat (SSR) markers derived from Dipteronia have been described. After Illumina pair-end sequencing, approximately 93.2 million reads were generated and assembled to yield a total of 99,358 unigenes. A majority of these unigenes (53%, 52,789) had at least one blast hit against the public protein databases. Further, 12,377 SSR loci were detected and 4179 primer pairs were designed for experimental validation. Of these 4179 primer pairs, 435 primer pairs were randomly selected to test polymorphism. Our results show that products from 132 primer pairs were polymorphic, in which 97 polymorphic SSR markers were further selected to analyze the genetic diversity of 10 natural populations of Dipteronia. The identification of SSR markers during our research will provide the much valuable data for population genetic analyses and evolutionary studies in Dipteronia. PMID- 26907246 TI - Typical Monoterpenes as Insecticides and Repellents against Stored Grain Pests. AB - Five monoterpenes naturally occurring in essential oils were tested for their insecticidal and repellent activities against the bruchid beetle Callosobruchus maculatus and the maize weevil Sitophilus zeamais. The monoterpenes were highly efficient as inducers of mortality or repellency against both insect species. They were more efficient in their fumigant activity against C. maculatus than against S. zeamais, while this profile of action was inverted when considering the repellent activities. Eugenol was one the most effective fumigants against both insects and one the most effective repellent against C. maculatus, while citronellal and geranial were one the most effective repellents against S. zeamais. Functional and positional isomerism of the monoterpenes pairs appears to exert little or no influence on theirs effects, especially in case of repellency. The validation of the insecticidal/repellent efficacy of isolated monoterpenes may permit a more advantageous, rapid, economic and optimized approach to the identification of promising oils for commercial formulations when combined with ethnobotanical strategies. PMID- 26907247 TI - Synthesis of 5,10-bis(Trifluoromethyl) Substituted beta-Octamethylporphyrins and Central-Metal-Dependent Solvolysis of Their meso-Trifluoromethyl Groups. AB - 5,10-Bistrifluoromethyl substituted beta-octamethylporphyrins were synthesized via a scrambling side reaction of a dipyrromethane precursor in the presence of a large excess of trifluoroacetic acid. Compared with the trans-analogs, the cis analogs of meso-trifluoromethyl beta-octaalkylporphyrin showed more red-shifted absorption bands. These meso-trifluoromethyl derivatives of beta octaalkylporphyrins underwent smooth metalation, similar to other common porphyrins, however, the corresponding zinc complexes underwent a type of solvolysis, whereby the trifluoromethyl groups were converted into methoxycarbonyl groups by the methanol used as solvent. UV-visible absorption spectra and X-ray crystal structure analyses revealed that the presence of a methoxycarbonyl substituent did not influence the deformation of the molecular framework and its absorption properties; this is because the methoxycarbonyl has a planar and perpendicular geometry, as opposed to the relatively bulky trifluoromethyl substituent. PMID- 26907248 TI - Phenolic Compounds in Chilean Mistletoe (Quintral, Tristerix tetrandus) Analyzed by UHPLC-Q/Orbitrap/MS/MS and Its Antioxidant Properties. AB - Mass spectrometry has become a method of choice to characterize bioactive compounds in biological samples because of its sensitivity and selectivity. Hybrid ultra-HPLC hyphenated with Orbitrap mass analyzer is an innovative state of the art technology that allows fast and accurate metabolomic analyses. In this work the metabolites of a Chilean mistletoe endemic to the VIII region of Chile were investigated for the first time using UHPLC mass analysis (UHPLC-PDA-HESI Orbitrap MS(n)). The anthocyanins, together with the non-pigmented phenolics were fingerprinted and correlated with the antioxidant capacities measured by the bleaching of the DPPH radical, the ferric reducing antioxidant power (FRAP), the superoxide anion scavenging activity assay (SA), and total content of phenolics, flavonoids and anthocyanins measured by spectroscopic methods. Six anthocyanins were identified, and among them, the 3-O-glycosides of delphinidin and cyanidin were the major ones. In addition, several phenolic acids (including feruloylquinic acid, feruloyl glucose, chlorogenic acid) and several flavonols (luteolin, quercetin, apigenin, isorhamnetin and glycoside derivatives) were also identified. The mistletoe leaves showed the highest antioxidant activity as measured by the DPPH radical bleaching, ferric reducing antioxidant power and superoxide anion scavenging activity tests (13.38 +/- 0.47 ug/mL, 125.32 +/- 5.96 umolTE/g DW and 84.06 +/- 4.59 at 100 ug/mL, respectively). PMID- 26907249 TI - In Vivo Cardiotoxicity Induced by Sodium Aescinate in Zebrafish Larvae. AB - Sodium aescinate (SA) is a widely-applied triterpene saponin product derived from horse chestnut seeds, possessing vasoactive and organ-protective activities with oral or injection administration in the clinic. To date, no toxicity or adverse events in SA have been reported, by using routine models (in vivo or in vitro), which are insufficient to predict all aspects of its pharmacological and toxicological actions. In this study, taking advantage of transparent zebrafish larvae (Danio rerio), we evaluated cardiovascular toxicity of SA at doses of 1/10 MNLC, 1/3 MNLC, MNLC and LC10 by yolk sac microinjection. The qualitative and quantitative cardiotoxicity in zebrafish was assessed at 48 h post-SA treatment, using specific phenotypic endpoints: heart rate, heart rhythm, heart malformation, pericardial edema, circulation abnormalities, thrombosis and hemorrhage. The results showed that SA at 1/10 MNLC and above doses could induce obvious cardiac and pericardial malformations, whilst 1/3 MNLC and above doses could induce significant cardiac malfunctions (heart rate and circulation decrease/absence), as compared to untreated or vehicle-treated control groups. Such cardiotoxic manifestations occurred in more than 50% to 100% of all zebrafish treated with SA at MNLC and LC10. Our findings have uncovered the potential cardiotoxicity of SA for the first time, suggesting more attention to the risk of its clinical application. Such a time- and cost-saving zebrafish cardiotoxicity assay is very valid and reliable for rapid prediction of compound toxicity during drug research and development. PMID- 26907250 TI - Offspring Number Does Not Influence Reaching the Disability's Milestones in Multiple Sclerosis: A Seven-Year Follow-Up Study. AB - OBJECTIVES: Data on pregnancy long-term effects on multiple sclerosis (MS) course are still controversial; whether experiencing more than one pregnancy exposes one to risk of the disability's accrual is still unknown. We investigated differences existing in terms of disability progression among women with MS (wwMS) who had one or more children after their MS onset. METHODS: Monoparous and multiparous wwMS were enrolled from the Catania MS Center, Italy, in a monocenter retrospective study. A Cox proportional hazards model was used to examine the effect of the number of parities on time from MS disease onset to EDSS 4.0 and 6.0. The study protocol was approved by the local Ethical Committee. RESULTS: During the seven years of observation, 32.1% and 23.2% of the monoparous group reached expanded disability disease status (EDSS) 4.0 and 6.0 respectively, compared to 13.3% and 3.3% of the multiparous group (p = 0.057 and p = 0.017; respectively). The Kaplan-Meier curve analysis showed no statistically significant differences between the two groups in reaching the two milestones. The multiparous group showed a longer time to reach the EDSS 4.0 (3.5 vs. 2.6 years, log-rank 0.57, p = 0.45). The Cox regression analysis showed that the EDSS at the time of first pregnancy (Exp(B) 9.4, CI 4.5-19.7, p< 0.001) and the time from MS onset to first pregnancy (Exp(B) 0.96, CI = 0.93-0.98, p < 0.05) were significant predictors of reaching the EDSS 4.0, whereas a model including only the EDSS one year after the first pregnancy significantly predicted (Exp(B) value of 6.4, CI 2.6-15.4, p < 0.001) the reaching of EDSS 6.0. CONCLUSIONS: Our results suggest that experiencing more than one pregnancy could not convey a different clinical outcome in wwMS. Further research is needed to confirm our results. PMID- 26907251 TI - Hyaluronidase Inhibitory Activity of Pentacylic Triterpenoids from Prismatomeris tetrandra (Roxb.) K. Schum: Isolation, Synthesis and QSAR Study. AB - The mammalian hyaluronidase degrades hyaluronic acid by the cleavage of the beta 1,4-glycosidic bond furnishing a tetrasaccharide molecule as the main product which is a highly angiogenic and potent inducer of inflammatory cytokines. Ursolic acid 1, isolated from Prismatomeris tetrandra, was identified as having the potential to develop inhibitors of hyaluronidase. A series of ursolic acid analogues were either synthesized via structure modification of ursolic acid 1 or commercially obtained. The evaluation of the inhibitory activity of these compounds on the hyaluronidase enzyme was conducted. Several structural, topological and quantum chemical descriptors for these compounds were calculated using semi empirical quantum chemical methods. A quantitative structure activity relationship study (QSAR) was performed to correlate these descriptors with the hyaluronidase inhibitory activity. The statistical characteristics provided by the best multi linear model (BML) (R2 = 0.9717, R2cv = 0.9506) indicated satisfactory stability and predictive ability of the developed model. The in silico molecular docking study which was used to determine the binding interactions revealed that the ursolic acid analog 22 had a strong affinity towards human hyaluronidase. PMID- 26907252 TI - Drosophotoxicology: An Emerging Research Area for Assessing Nanoparticles Interaction with Living Organisms. AB - The rapid development of nanotechnology allowed the fabrication of a wide range of different nanomaterials, raising many questions about their safety and potential risks for the human health and environment. Most of the current nanotoxicology research is not standardized, hampering any comparison or reproducibility of the obtained results. Drosophotoxicology encompasses the plethora of methodological approaches addressing the use of Drosophila melanogaster as a choice organism in toxicology studies. Drosophila melanogaster model offers several important advantages, such as a relatively simple genome structure, short lifespan, low maintenance cost, readiness of experimental manipulation comparative to vertebrate models from both ethical and technical points of view, relevant gene homology with higher organisms, and ease of obtaining mutant phenotypes. The molecular pathways, as well as multiple behavioral and developmental parameters, can be evaluated using this model in lower, medium or high throughput type assays, allowing a systematic classification of the toxicity levels of different nanomaterials. The purpose of this paper is to review the current research on the applications of Drosophila melanogaster model for the in vivo assessment of nanoparticles toxicity and to reveal the huge potential of this model system to provide results that could enable a proper selection of different nanostructures for a certain biomedical application. PMID- 26907253 TI - Effect of the Solvent Temperatures on Dynamics of Serine Protease Proteinase K. AB - To obtain detailed information about the effect of the solvent temperatures on protein dynamics, multiple long molecular dynamics (MD) simulations of serine protease proteinase K with the solute and solvent coupled to different temperatures (either 300 or 180 K) have been performed. Comparative analyses demonstrate that the internal flexibility and mobility of proteinase K are strongly dependent on the solvent temperatures but weakly on the protein temperatures. The constructed free energy landscapes (FELs) at the high solvent temperatures exhibit a more rugged surface, broader spanning range, and higher minimum free energy level than do those at the low solvent temperatures. Comparison between the dynamic hydrogen bond (HB) numbers reveals that the high solvent temperatures intensify the competitive HB interactions between water molecules and protein surface atoms, and this in turn exacerbates the competitive HB interactions between protein internal atoms, thus enhancing the conformational flexibility and facilitating the collective motions of the protein. A refined FEL model was proposed to explain the role of the solvent mobility in facilitating the cascade amplification of microscopic motions of atoms and atomic groups into the global collective motions of the protein. PMID- 26907254 TI - Deletion of Phytochelatin Synthase Modulates the Metal Accumulation Pattern of Cadmium Exposed C. elegans. AB - Environmental metal pollution is a growing health risk to flora and fauna. It is therefore important to fully elucidate metal detoxification pathways. Phytochelatin synthase (PCS), an enzyme involved in the biosynthesis of phytochelatins (PCs), plays an important role in cadmium detoxification. The PCS and PCs are however not restricted to plants, but are also present in some lower metazoans. The model nematode Caenorhabditis elegans, for example, contains a fully functional phytochelatin synthase and phytochelatin pathway. By means of a transgenic nematode strain expressing a pcs-1 promoter-tagged GFP (pcs-1::GFP) and a pcs-1 specific qPCR assay, further evidence is presented that the expression of the C. elegans phytochelatin synthase gene (pcs-1) is transcriptionally non-responsive to a chronic (48 h) insult of high levels of zinc (500 MUM) or acute (3 h) exposures to high levels of cadmium (300 MUM). However, the accumulation of cadmium, but not zinc, is dependent on the pcs-1 status of the nematode. Synchrotron based X-ray fluorescence imaging uncovered that the cadmium body burden increased significantly in the pcs-1(tm1748) knockout allele. Taken together, this suggests that whilst the transcription of pcs-1 may not be mediated by an exposure zinc or cadmium, it is nevertheless an integral part of the cadmium detoxification pathway in C. elegans. PMID- 26907255 TI - Recent Advances in Disease Modeling and Drug Discovery for Diabetes Mellitus Using Induced Pluripotent Stem Cells. AB - Diabetes mellitus (DM) is a widespread metabolic disease with a progressive incidence of morbidity and mortality worldwide. Despite extensive research, treatment options for diabetic patients remains limited. Although significant challenges remain, induced pluripotent stem cells (iPSCs) have the capacity to differentiate into any cell type, including insulin-secreting pancreatic beta cells, highlighting its potential as a treatment option for DM. Several iPSC lines have recently been derived from both diabetic and healthy donors. Using different reprogramming techniques, iPSCs were differentiated into insulin secreting pancreatic betacells. Furthermore, diabetes patient-derived iPSCs (DiPSCs) are increasingly being used as a platform to perform cell-based drug screening in order to develop DiPSC-based cell therapies against DM. Toxicity and teratogenicity assays based on iPSC-derived cells can also provide additional information on safety before advancing drugs to clinical trials. In this review, we summarize recent advances in the development of techniques for differentiation of iPSCs or DiPSCs into insulin-secreting pancreatic beta cells, their applications in drug screening, and their role in complementing and replacing animal testing in clinical use. Advances in iPSC technologies will provide new knowledge needed to develop patient-specific iPSC-based diabetic therapies. PMID- 26907256 TI - Prenylated Flavonoids from Cudrania tricuspidata Suppress Lipopolysaccharide Induced Neuroinflammatory Activities in BV2 Microglial Cells. AB - In Korea and China, Cudrania tricuspidata Bureau (Moraceae) is an important traditional medicinal plant used to treat lumbago, hemoptysis, and contusions. The C. tricuspidata methanol extract suppressed both production of NO and PGE2 in BV2 microglial cells. Cudraflavanone D (1), isolated from this extract, remarkably suppressed the protein expression of inducible NO synthase and cyclooxygenase-2, and decreased the levels of NO and PGE2 in BV2 microglial cells exposed to lipopolysaccharide. Cudraflavanone D (1) also decreased IL-6, TNF alpha, IL-12, and IL-1beta production, blocked nuclear translocation of NF-kappaB heterodimers (p50 and p65) by interrupting the degradation and phosphorylation of inhibitor of IkappaB-alpha, and inhibited NF-kappaB binding. In addition, cudraflavanone D (1) suppressed the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 MAPK pathways. This study indicated that cudraflavanone D (1) can be a potential drug candidate for the cure of neuroinflammation. PMID- 26907257 TI - In Silico Screening Identifies a Novel Potential PARP1 Inhibitor Targeting Synthetic Lethality in Cancer Treatment. AB - Synthetic lethality describes situations in which defects in two different genes or pathways together result in cell death. This concept has been applied to drug development for cancer treatment, as represented by Poly (ADP-ribose) polymerase (PARPs) inhibitors. In the current study, we performed a computational screening to discover new PARP inhibitors. Among the 11,247 compounds analyzed, one natural product, ZINC67913374, stood out by its superior performance in the simulation analyses. Compared with the FDA approved PARP1 inhibitor, olaparib, our results demonstrated that the ZINC67913374 compound achieved a better grid score (-86.8) and amber score (-51.42). Molecular dynamics simulations suggested that the PARP1 ZINC67913374 complex was more stable than olaparib. The binding free energy for ZINC67913374 was -177.28 kJ/mol while that of olaparib was -159.16 kJ/mol. These results indicated ZINC67913374 bound to PARP1 with a higher affinity, which suggest ZINC67913374 has promising potential for cancer drug development. PMID- 26907258 TI - Assessment of Radiation Induced Therapeutic Effect and Cytotoxicity in Cancer Patients Based on Transcriptomic Profiling. AB - Toxicity induced by radiation therapy is a curse for cancer patients undergoing treatment. It is imperative to understand and define an ideal condition where the positive effects notably outweigh the negative. We used a microarray meta analysis approach to measure global gene-expression before and after radiation exposure. Bioinformatic tools were used for pathways, network, gene ontology and toxicity related studies. We found 429 differentially expressed genes at fold change >2 and p-value <0.05. The most significantly upregulated genes were synuclein alpha (SNCA), carbonic anhydrase I (CA1), X-linked Kx blood group (XK), glycophorin A and B (GYPA and GYPB), and hemogen (HEMGN), while downregulated ones were membrane-spanning 4-domains, subfamily A member 1 (MS4A1), immunoglobulin heavy constant mu (IGHM), chemokine (C-C motif) receptor 7 (CCR7), BTB and CNC homology 1 transcription factor 2 (BACH2), and B-cell CLL/lymphoma 11B (BCL11B). Pathway analysis revealed calcium-induced T lymphocyte apoptosis and the role of nuclear factor of activated T-cells (NFAT) in regulation of the immune response as the most inhibited pathways, while apoptosis signaling was significantly activated. Most of the normal biofunctions were significantly decreased while cell death and survival process were activated. Gene ontology enrichment analysis revealed the immune system process as the most overrepresented group under the biological process category. Toxicity function analysis identified liver, kidney and heart to be the most affected organs during and after radiation therapy. The identified biomarkers and alterations in molecular pathways induced by radiation therapy should be further investigated to reduce the cytotoxicity and development of fatigue. PMID- 26907259 TI - Transcriptome-Based Identification of Differently Expressed Genes from Xanthomonas oryzae pv. oryzae Strains Exhibiting Different Virulence in Rice Varieties. AB - Xanthomonas oryzae pv. oryzae (Xoo) causes bacterial blight (BB) in rice (Oryza sativa L.). In this study, we investigated the genome-wide transcription patterns of two Xoo strains (KACC10331 and HB1009), which showed different virulence patterns against eight rice cultivars, including IRBB21 (carrying Xa21). In total, 743 genes showed a significant change (p-value < 0.001 in t-tests) in their mRNA expression levels in the HB1009 (K3a race) strain compared with the Xoo KACC10331 strain (K1 race). Among them, four remarkably enriched GO terms, DNA binding, transposition, cellular nitrogen compound metabolic process, and cellular macromolecule metabolic process, were identified in the upregulated genes. In addition, the expression of 44 genes was considerably higher (log2 fold changes > 2) in the HB1009 (K3a race) strain than in the Xoo KACC10331 (K1 race) strain. Furthermore, 13 and 12 genes involved in hypersensitive response and pathogenicity (hrp) and two-component regulatory systems (TCSs), respectively, were upregulated in the HB1009 (K3a race) strain compared with the Xoo KACC10331 (K1 race) strain, which we determined using either quantitative real-time PCR analysis or next-generation RNA sequencing. These results will be helpful to improve our understanding of Xoo and to gain a better insight into the Xoo-rice interactions. PMID- 26907260 TI - Synthetic Human TLR9-LRR11 Peptide Attenuates TLR9 Signaling by Binding to and thus Decreasing Internalization of CpG Oligodeoxynucleotides. AB - Toll-like receptor (TLR) 9 is an endosomal receptor recognizing bacterial DNA/CpG containing oligodeoxynucleotides (CpG ODN). Blocking CpG ODN/TLR9 activity represents a strategy for therapeutic prevention of immune system overactivation. Herein, we report that a synthetic peptide (SP) representing the leucine-rich repeat 11 subdomain of the human TLR9 extracellular domain could attenuate CpG ODN/TLR9 activity in RAW264.7 cells by binding to CpG ODN and decreasing its internalization. Our results demonstrate that preincubation with SP specifically inhibited CpG ODN- but not lipopolysaccharide (LPS)- and lipopeptide (PAM3CSK4) stimulated TNF-alpha and IL-6 release. Preincubation of SP with CpG ODN dose dependently decreased TLR9-driven phosphorylation of IkappaBalpha and ERK and activation of NF-kappaB/p65. Moreover, SP dose-dependently decreased FAM-labeled CpG ODN internalization, whereas non-labeled CpG ODN reversed the inhibition. The KD value of SP-CpG ODN binding was within the micromolar range. Our results demonstrated that SP was a specific inhibitor of CpG ODN/TLR9 activity via binding to CpG ODN, leading to reduced ODN internalization and decreased activation of subsequent pathways within cells. Thus, SP could be used as a potential CpG ODN antagonist to block TLR9 signaling. PMID- 26907261 TI - Intracellular Delivery of Proteins with Cell-Penetrating Peptides for Therapeutic Uses in Human Disease. AB - Protein therapy exhibits several advantages over small molecule drugs and is increasingly being developed for the treatment of disorders ranging from single enzyme deficiencies to cancer. Cell-penetrating peptides (CPPs), a group of small peptides capable of promoting transport of molecular cargo across the plasma membrane, have become important tools in promoting the cellular uptake of exogenously delivered proteins. Although the molecular mechanisms of uptake are not firmly established, CPPs have been empirically shown to promote uptake of various molecules, including large proteins over 100 kiloDaltons (kDa). Recombinant proteins that include a CPP tag to promote intracellular delivery show promise as therapeutic agents with encouraging success rates in both animal and human trials. This review highlights recent advances in protein-CPP therapy and discusses optimization strategies and potential detrimental effects. PMID- 26907262 TI - Chalcone-Induced Apoptosis through Caspase-Dependent Intrinsic Pathways in Human Hepatocellular Carcinoma Cells. AB - Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers worldwide. Chemoprevention of HCC can be achieved through the use of natural or synthetic compounds that reverse, suppress or prevent the development of cancer progression. In this study, we investigated the antiproliferative effects and the mechanism of action of two compounds, 2,3,4'-trimethoxy-2'-hydroxy-chalcone (CH1) and 3'-bromo-3,4-dimethoxy-chalcone (CH2), over human hepatoma cells (HepG2 and Huh-7) and cultured mouse hepatocytes (HepM). Cytotoxic effects were observed over the HepG2 and Huh-7, and no effects were observed over the HepM. For HepG2 cells, treated separately with each chalcone, typical apoptotic laddering and nuclear condensation were observed. Additionally, the caspases and Bcl-2 family proteins activation by using Western blotting and immunocytochemistry were studied. Caspase-8 was not activated, but caspase-3 and -9 were both activated by chalcones in HepG2 cells. Chalcones also induced reactive oxygen species (ROS) accumulation after 4, 8 and 24 h of treatment in HepG2 cells. These results suggest that apoptosis in HepG2 was induced through: (i) a caspase-dependent intrinsic pathway; and (ii) by alterations in the cellular levels of Bcl-2 family proteins, and also, that the chalcone moiety could be a potent candidate as novel anticancer agents acting on human hepatomas. PMID- 26907263 TI - Identification and Evolution of Functional Alleles of the Previously Described Pollen Specific Myrosinase Pseudogene AtTGG6 in Arabidopsis thaliana. AB - Myrosinases are beta-thioglucoside glucohydrolases and serve as defense mechanisms against insect pests and pathogens by producing toxic compounds. AtTGG6 in Arabidopsis thaliana was previously reported to be a myrosinase pseudogene but specifically expressed in pollen. However, we found that AlTGG6, an ortholog to AtTGG6 in A. lyrata (an outcrossing relative of A. thaliana) was functional, suggesting that functional AtTGG6 alleles may still exist in A. thaliana. AtTGG6 alleles in 29 A. thaliana ecotypes were cloned and sequenced. Results indicate that ten alleles were functional and encoded Myr II type myrosinase of 512 amino acids, and myrosinase activity was confirmed by overexpressing AtTGG6 in Pichia pastoris. However, the 19 other ecotypes had disabled alleles with highly polymorphic frame-shift mutations and diversified sequences. Thirteen frame-shift mutation types were identified, which occurred independently many times in the evolutionary history within a few thousand years. The functional allele was expressed specifically in pollen similar to the disabled alleles but at a higher expression level, suggesting its role in defense of pollen against insect pests such as pollen beetles. However, the defense function may have become less critical after A. thaliana evolved to self fertilization, and thus resulted in loss of function in most ecotypes. PMID- 26907264 TI - Cloning and Characterization of a Flavonoid 3'-Hydroxylase Gene from Tea Plant (Camellia sinensis). AB - Tea leaves contain abundant flavan-3-ols, which include dihydroxylated and trihydroxylated catechins. Flavonoid 3'-hydroxylase (F3'H: EC 1.14.13.21) is one of the enzymes in the establishment of the hydroxylation pattern. A gene encoding F3'H, designated as CsF3'H, was isolated from Camellia sinensis with a homology based cloning technique and deposited in the GenBank (GenBank ID: KT180309). Bioinformatic analysis revealed that CsF3'H was highly homologous with the characterized F3'Hs from other plant species. Four conserved cytochrome P450 featured motifs and three F3'H-specific conserved motifs were discovered in the protein sequence of CsF3'H. Enzymatic analysis of the heterologously expressed CsF3'H in yeast demonstrated that tea F3'H catalyzed the 3'-hydroxylation of naringenin, dihydrokaempferol and kaempferol. Apparent Km values for these substrates were 17.08, 143.64 and 68.06 MUM, and their apparent Vmax values were 0.98, 0.19 and 0.44 pM.min(-1), respectively. Transcription level of CsF3'H in the new shoots, during tea seed germination was measured, along with that of other key genes for flavonoid biosynthesis using real-time PCR technique. The changes in 3',4'-flavan-3-ols, 3',4',5'-flavan-3-ols and flavan-3-ols, were consistent with the expression level of CsF3'H and other related genes in the leaves. In the study of nitrogen supply for the tea plant growth, our results showed the expression level of CsF3'H and all other tested genes increased in response to nitrogen depletion after 12 days of treatment, in agreement with a corresponding increase in 3',4'-catechins, 3',4',5'-catechins and flavan 3-ols content in the leaves. All these results suggest the importance of CsF3'H in the biosynthesis of 3',4'-catechins, 3',4',5'-catechins and flavan 3-ols in tea leaves. PMID- 26907265 TI - Benzyl Isothiocyanate Inhibits Prostate Cancer Development in the Transgenic Adenocarcinoma Mouse Prostate (TRAMP) Model, Which Is Associated with the Induction of Cell Cycle G1 Arrest. AB - Benzyl isothiocyanate (BITC) is a hydrolysis product of glucotropaeolin, a compound found in cruciferous vegetables, and has been shown to have anti-tumor properties. In the present study, we investigated whether BITC inhibits the development of prostate cancer in the transgenic adenocarcinoma mouse prostate (TRAMP) mice. Five-week old, male TRAMP mice and their nontransgenic littermates were gavage-fed with 0, 5, or 10 mg/kg of BITC every day for 19 weeks. The weight of the genitourinary tract increased markedly in TRAMP mice and this increase was suppressed significantly by BITC feeding. H and E staining of the dorsolateral lobes of the prostate demonstrated that well-differentiated carcinoma (WDC) was a predominant feature in the TRAMP mice. The number of lobes with WDC was reduced by BITC feeding while that of lobes with prostatic intraepithelial neoplasia was increased. BITC feeding reduced the number of cells expressing Ki67 (a proliferation marker), cyclin A, cyclin D1, and cyclin-dependent kinase (CDK)2 in the prostatic tissue. In vitro cell culture results revealed that BITC decreased DNA synthesis, as well as CDK2 and CDK4 activity in TRAMP-C2 mouse prostate cancer cells. These results indicate that inhibition of cell cycle progression contributes to the inhibition of prostate cancer development in TRAMP mice treated with BITC. PMID- 26907266 TI - Exploring the Role of Different Neonatal Nutrition Regimens during the First Week of Life by Urinary GC-MS Metabolomics. AB - In this study, a gas-chromatography mass spectrometry (GC-MS) metabolomics study was applied to examine urine metabolite profiles of different classes of neonates under different nutrition regimens. The study population included 35 neonates, exclusively either breastfed or formula milk fed, in a seven-day timeframe. Urine samples were collected from intrauterine growth restriction (IUGR), large for gestational age (LGA), and appropriate gestational age (AGA) neonates. At birth, IUGR and LGA neonates showed similarities in their urine metabolite profiles that differed from AGA. When neonates started milk feeding, their metabolite excretion profile was strongly characterized by the different diet regimens. After three days of formula milk nutrition, urine had higher levels of glucose, galactose, glycine and myo-inositol, while up-regulated aconitic acid, aminomalonic acid and adipic acid were found in breast milk fed neonates. At seven days, neonates fed with formula milk shared higher levels of pseudouridine with IUGR and LGA at birth. Breastfed neonates shared up-regulated pyroglutamic acid, citric acid, and homoserine, with AGA at birth. The role of most important metabolites is herein discussed. PMID- 26907267 TI - Endogenous Sulfur Dioxide Inhibits Vascular Calcification in Association with the TGF-beta/Smad Signaling Pathway. AB - The study was designed to investigate whether endogenous sulfur dioxide (SO2) plays a role in vascular calcification (VC) in rats and its possible mechanisms. In vivo medial vascular calcification was induced in rats by vitamin D3 and nicotine for four weeks. In vitro calcification of cultured A7r5 vascular smooth muscle cells (VSMCs) was induced by calcifying media containing 5 mmol/L CaCl2. Aortic smooth muscle (SM) alpha-actin, runt-related transcription factor 2 (Runx2), transforming growth factor-beta (TGF-beta) and Smad expression was measured. VC rats showed dispersed calcified nodules among the elastic fibers in calcified aorta with increased aortic calcium content and alkaline phosphatase (ALP) activity. SM alpha-actin was markedly decreased, but the osteochondrogenic marker Runx2 concomitantly increased and TGF-beta/Smad signaling was activated, in association with the downregulated SO2/aspartate aminotransferase (AAT) pathway. However, SO2 supplementation successfully ameliorated vascular calcification, and increased SM alpha-actin expression, but inhibited Runx2 and TGF-beta/Smad expression. In calcified A7r5 VSMCs, the endogenous SO2/AAT pathway was significantly downregulated. SO2 treatment reduced the calcium deposits, calcium content, ALP activity and Runx2 expression and downregulated the TGF beta/Smad pathway in A7r5 cells but increased SM alpha-actin expression. In brief, SO2 significantly ameliorated vascular calcification in association with downregulation of the TGF-beta/Smad pathway. PMID- 26907268 TI - The Protective Role of the TOPK/PBK Pathway in Myocardial Ischemia/Reperfusion and H2O2-Induced Injury in H9C2 Cardiomyocytes. AB - T-LAK-cell-originated protein kinase (TOPK) is a PDZ-binding kinase (PBK) that was recently identified as a novel member of the mitogen-activated protein kinase (MAPK) family. It has been shown to play an important role in many cellular functions. However, its role in cardiac function remains unclear. Thus, we have herein explored the biological function of TOPK in myocardial ischemia/reperfusion (I/R) and oxidative stress injury in H9C2 cardiomyocytes. I/R and ischemic preconditioning (IPC) were induced in rats by 3-hour reperfusion after 30-min occlusion of the left anterior descending coronary artery and by 3 cycles of 5-min I/R. Hydrogen peroxide (H2O2) was used to induce oxidative stress in H9C2 cardiomyocytes. TOPK expression was analyzed by western blotting, RT-PCR, immunohistochemical staining, and immunofluorescence imaging studies. The effects of TOPK gene overexpression and its inhibition via its inhibitor HI-TOPK-032 on cell viability and Bcl-2, Bax, ERK1/2, and p-ERK1/2 protein expression were analyzed by MTS assay and western blotting, respectively. The results showed that IPC alleviated myocardial I/R injury and induced TOPK activation. Furthermore, H2O2 induced TOPK phosphorylation in a time-dependent manner. Interestingly, TOPK inhibition aggravated the H2O2-induced oxidative stress injury in myocardiocytes, whereas overexpression relieved it. In addition, the ERK pathway was positively regulated by TOPK signaling. In conclusion, our results indicate that TOPK might mediate a novel survival signal in myocardial I/R, and that its effect on anti oxidative stress involves the ERK signaling pathway. PMID- 26907269 TI - Genome-Wide Identification and Transcriptome-Based Expression Profiling of the Sox Gene Family in the Nile Tilapia (Oreochromis niloticus). AB - The Sox transcription factor family is characterized with the presence of a Sry related high-mobility group (HMG) box and plays important roles in various biological processes in animals, including sex determination and differentiation, and the development of multiple organs. In this study, 27 Sox genes were identified in the genome of the Nile tilapia (Oreochromis niloticus), and were classified into seven groups. The members of each group of the tilapia Sox genes exhibited a relatively conserved exon-intron structure. Comparative analysis showed that the Sox gene family has undergone an expansion in tilapia and other teleost fishes following their whole genome duplication, and group K only exists in teleosts. Transcriptome-based analysis demonstrated that most of the tilapia Sox genes presented stage-specific and/or sex-dimorphic expressions during gonadal development, and six of the group B Sox genes were specifically expressed in the adult brain. Our results provide a better understanding of gene structure and spatio-temporal expression of the Sox gene family in tilapia, and will be useful for further deciphering the roles of the Sox genes during sex determination and gonadal development in teleosts. PMID- 26907271 TI - Removing the Interdependency between Horizontal and Vertical Eye-Movement Components in Electrooculograms. AB - This paper introduces a method to remove the unwanted interdependency between vertical and horizontal eye-movement components in electrooculograms (EOGs). EOGs have been widely used to estimate eye movements without a camera in a variety of human-computer interaction (HCI) applications using pairs of electrodes generally attached either above and below the eye (vertical EOG) or to the left and right of the eyes (horizontal EOG). It has been well documented that the vertical EOG component has less stability than the horizontal EOG one, making accurate estimation of the vertical location of the eyes difficult. To address this issue, an experiment was designed in which ten subjects participated. Visual inspection of the recorded EOG signals showed that the vertical EOG component is highly influenced by horizontal eye movements, whereas the horizontal EOG is rarely affected by vertical eye movements. Moreover, the results showed that this interdependency could be effectively removed by introducing an individual constant value. It is therefore expected that the proposed method can enhance the overall performance of practical EOG-based eye-tracking systems. PMID- 26907270 TI - Expression Patterns of Genes Involved in Ascorbate-Glutathione Cycle in Aphid Infested Maize (Zea mays L.) Seedlings. AB - Reduced forms of ascorbate (AsA) and glutathione (GSH) are among the most important non-enzymatic foliar antioxidants in maize (Zea mays L.). The survey was aimed to evaluate impact of bird cherry-oat aphid (Rhopalosiphum padi L.) or grain aphid (Sitobion avenae F.) herbivory on expression of genes related to ascorbate-glutathione (AsA-GSH) cycle in seedlings of six maize varieties (Ambrozja, Nana, Tasty Sweet, Touran, Waza, Zlota Karlowa), differing in resistance to the cereal aphids. Relative expression of sixteen maize genes encoding isoenzymes of ascorbate peroxidase (APX1, APX2, APX3, APX4, APX5, APX6, APX7), monodehydroascorbate reductase (MDHAR1, MDHAR2, MDHAR3, MDHAR4), dehydroascorbate reductase (DHAR1, DHAR2, DHAR3) and glutathione reductase (GR1, GR2) was quantified. Furthermore, effect of hemipterans' attack on activity of APX, MDHAR, DHAR and GR enzymes, and the content of reduced and oxidized ascorbate and glutathione in maize plants were assessed. Seedling leaves of more resistant Z. mays varieties responded higher elevations in abundance of target transcripts. In addition, earlier and stronger aphid-triggered changes in activity of APX, MDHAR, DHAR and GR enzymes, and greater modulations in amount of the analyzed antioxidative metabolites were detected in foliar tissues of highly resistant Ambrozja genotype in relation to susceptible Tasty Sweet plants. PMID- 26907272 TI - A Game Theory Algorithm for Intra-Cluster Data Aggregation in a Vehicular Ad Hoc Network. AB - Vehicular ad hoc networks (VANETs) have an important role in urban management and planning. The effective integration of vehicle information in VANETs is critical to traffic analysis, large-scale vehicle route planning and intelligent transportation scheduling. However, given the limitations in the precision of the output information of a single sensor and the difficulty of information sharing among various sensors in a highly dynamic VANET, effectively performing data aggregation in VANETs remains a challenge. Moreover, current studies have mainly focused on data aggregation in large-scale environments but have rarely discussed the issue of intra-cluster data aggregation in VANETs. In this study, we propose a multi-player game theory algorithm for intra-cluster data aggregation in VANETs by analyzing the competitive and cooperative relationships among sensor nodes. Several sensor-centric metrics are proposed to measure the data redundancy and stability of a cluster. We then study the utility function to achieve efficient intra-cluster data aggregation by considering both data redundancy and cluster stability. In particular, we prove the existence of a unique Nash equilibrium in the game model, and conduct extensive experiments to validate the proposed algorithm. Results demonstrate that the proposed algorithm has advantages over typical data aggregation algorithms in both accuracy and efficiency. PMID- 26907273 TI - Angle-Polarization Estimation for Coherent Sources with Linear Tripole Sensor Arrays. AB - We propose a parallel factor (PARAFAC) analysis-based angle and polarization estimation algorithm for multiple coherent sources using a uniformly-spaced linear tripole sensor array. By forming a PARAFAC model using the spatial signature of the tripole array, the new algorithm requires neither spatial smoothing nor vector-field smoothing to decorrelate the signal coherency. We also establish that the angle-polarization parameters of K coherent signals can be uniquely determined by PARAFAC analysis, as long as the number of tripoles L >= 2K - 1 . In addition, the proposed algorithm can offer enhanced angle and polarization estimation accuracy by extending the interspacing of the tripoles beyond a half wavelength. PMID- 26907274 TI - Inspection Robot Based Mobile Sensing and Power Line Tracking for Smart Grid. AB - Smart sensing and power line tracking is very important in a smart grid system. Illegal electricity usage can be detected by remote current measurement on overhead power lines using an inspection robot. There is a need for accurate detection methods of illegal electricity usage. Stable and correct power line tracking is a very prominent issue. In order to correctly track and make accurate measurements, the swing path of a power line should be previously fitted and predicted by a mathematical function using an inspection robot. After this, the remote inspection robot can follow the power line and measure the current. This paper presents a new power line tracking method using parabolic and circle fitting algorithms for illegal electricity detection. We demonstrate the effectiveness of the proposed tracking method by simulation and experimental results. PMID- 26907275 TI - A Secure Scheme for Distributed Consensus Estimation against Data Falsification in Heterogeneous Wireless Sensor Networks. AB - Heterogeneous wireless sensor networks (HWSNs) can achieve more tasks and prolong the network lifetime. However, they are vulnerable to attacks from the environment or malicious nodes. This paper is concerned with the issues of a consensus secure scheme in HWSNs consisting of two types of sensor nodes. Sensor nodes (SNs) have more computation power, while relay nodes (RNs) with low power can only transmit information for sensor nodes. To address the security issues of distributed estimation in HWSNs, we apply the heterogeneity of responsibilities between the two types of sensors and then propose a parameter adjusted-based consensus scheme (PACS) to mitigate the effect of the malicious node. Finally, the convergence property is proven to be guaranteed, and the simulation results validate the effectiveness and efficiency of PACS. PMID- 26907276 TI - Hybrid EEG--Eye Tracker: Automatic Identification and Removal of Eye Movement and Blink Artifacts from Electroencephalographic Signal. AB - Contamination of eye movement and blink artifacts in Electroencephalogram (EEG) recording makes the analysis of EEG data more difficult and could result in mislead findings. Efficient removal of these artifacts from EEG data is an essential step in improving classification accuracy to develop the brain-computer interface (BCI). In this paper, we proposed an automatic framework based on independent component analysis (ICA) and system identification to identify and remove ocular artifacts from EEG data by using hybrid EEG and eye tracker system. The performance of the proposed algorithm is illustrated using experimental and standard EEG datasets. The proposed algorithm not only removes the ocular artifacts from artifactual zone but also preserves the neuronal activity related EEG signals in non-artifactual zone. The comparison with the two state-of-the-art techniques namely ADJUST based ICA and REGICA reveals the significant improved performance of the proposed algorithm for removing eye movement and blink artifacts from EEG data. Additionally, results demonstrate that the proposed algorithm can achieve lower relative error and higher mutual information values between corrected EEG and artifact-free EEG data. PMID- 26907277 TI - Social Milieu Oriented Routing: A New Dimension to Enhance Network Security in WSNs. AB - In large-scale wireless sensor networks (WSNs), in order to enhance network security, it is crucial for a trustor node to perform social milieu oriented routing to a target a trustee node to carry out trust evaluation. This challenging social milieu oriented routing with more than one end-to-end Quality of Trust (QoT) constraint has proved to be NP-complete. Heuristic algorithms with polynomial and pseudo-polynomial-time complexities are often used to deal with this challenging problem. However, existing solutions cannot guarantee the efficiency of searching; that is, they can hardly avoid obtaining partial optimal solutions during a searching process. Quantum annealing (QA) uses delocalization and tunneling to avoid falling into local minima without sacrificing execution time. This has been proven a promising way to many optimization problems in recently published literatures. In this paper, for the first time, with the help of a novel approach, that is, configuration path-integral Monte Carlo (CPIMC) simulations, a QA-based optimal social trust path (QA_OSTP) selection algorithm is applied to the extraction of the optimal social trust path in large-scale WSNs. Extensive experiments have been conducted, and the experiment results demonstrate that QA_OSTP outperforms its heuristic opponents. PMID- 26907279 TI - Cable Crosstalk Suppression with Two-Wire Voltage Feedback Method for Resistive Sensor Array. AB - Using a long, flexible test cable connected with a one-wire voltage feedback circuit, a resistive tactile sensor in a shared row-column fashion exhibited flexibility in robotic operations but suffered from crosstalk caused by the connected cable due to its wire resistances and its contacted resistances. Firstly, we designed a new non-scanned driving-electrode (VF-NSDE) circuit using two wires for every row line and every column line to reduce the crosstalk caused by the connected cables in the circuit. Then, an equivalent resistance expression of the element being tested (EBT) for the two-wire VF-NSDE circuit was analytically derived. Following this, the one-wire VF-NSDE circuit and the two wire VF-NSDE circuit were evaluated by simulation experiments. Finally, positive features of the proposed method were verified with the experiments of a two-wire VF-NSDE prototype circuit. The experiment results show that the two-wire VF-NSDE circuit can greatly reduce the crosstalk error caused by the cables in the 2-D networked resistive sensor array. PMID- 26907278 TI - A Vehicle Active Safety Model: Vehicle Speed Control Based on Driver Vigilance Detection Using Wearable EEG and Sparse Representation. AB - In this paper, we present a vehicle active safety model for vehicle speed control based on driver vigilance detection using low-cost, comfortable, wearable electroencephalographic (EEG) sensors and sparse representation. The proposed system consists of three main steps, namely wireless wearable EEG collection, driver vigilance detection, and vehicle speed control strategy. First of all, a homemade low-cost comfortable wearable brain-computer interface (BCI) system with eight channels is designed for collecting the driver's EEG signal. Second, wavelet de-noising and down-sample algorithms are utilized to enhance the quality of EEG data, and Fast Fourier Transformation (FFT) is adopted to extract the EEG power spectrum density (PSD). In this step, sparse representation classification combined with k-singular value decomposition (KSVD) is firstly introduced in PSD to estimate the driver's vigilance level. Finally, a novel safety strategy of vehicle speed control, which controls the electronic throttle opening and automatic braking after driver fatigue detection using the above method, is presented to avoid serious collisions and traffic accidents. The simulation and practical testing results demonstrate the feasibility of the vehicle active safety model. PMID- 26907280 TI - Improved Sensitivity MEMS Cantilever Sensor for Terahertz Photoacoustic Spectroscopy. AB - In this paper, a microelectromechanical system (MEMS) cantilever sensor was designed, modeled and fabricated to measure the terahertz (THz) radiation induced photoacoustic (PA) response of gases under low vacuum conditions. This work vastly improves cantilever sensitivity over previous efforts, by reducing internal beam stresses, minimizing out of plane beam curvature and optimizing beam damping. In addition, fabrication yield was improved by approximately 50% by filleting the cantilever's anchor and free end to help reduce high stress areas that occurred during device fabrication and processing. All of the cantilever sensors were fabricated using silicon-on-insulator (SOI) wafers and tested in a custom built, low-volume, vacuum chamber. The resulting cantilever sensors exhibited improved signal to noise ratios, sensitivities and normalized noise equivalent absorption (NNEA) coefficients of approximately 4.28 * 10(-10) cm( 1).WHz(-1/2). This reported NNEA represents approximately a 70% improvement over previously fabricated and tested SOI cantilever sensors for THz PA spectroscopy. PMID- 26907281 TI - Measurement and Modeling of Narrowband Channels for Ultrasonic Underwater Communications. AB - Underwater acoustic sensor networks are a promising technology that allow real time data collection in seas and oceans for a wide variety of applications. Smaller size and weight sensors can be achieved with working frequencies shifted from audio to the ultrasonic band. At these frequencies, the fading phenomena has a significant presence in the channel behavior, and the design of a reliable communication link between the network sensors will require a precise characterization of it. Fading in underwater channels has been previously measured and modeled in the audio band. However, there have been few attempts to study it at ultrasonic frequencies. In this paper, a campaign of measurements of ultrasonic underwater acoustic channels in Mediterranean shallow waters conducted by the authors is presented. These measurements are used to determine the parameters of the so-called kappa-MU shadowed distribution, a fading model with a direct connection to the underlying physical mechanisms. The model is then used to evaluate the capacity of the measured channels with a closed-form expression. PMID- 26907282 TI - Joint Transmit Antenna Selection and Power Allocation for ISDF Relaying Mobile-to Mobile Sensor Networks. AB - The outage probability (OP) performance of multiple-relay incremental-selective decode-and-forward (ISDF) relaying mobile-to-mobile (M2M) sensor networks with transmit antenna selection (TAS) over N-Nakagami fading channels is investigated. Exact closed-form OP expressions for both optimal and suboptimal TAS schemes are derived. The power allocation problem is formulated to determine the optimal division of transmit power between the broadcast and relay phases. The OP performance under different conditions is evaluated via numerical simulation to verify the analysis. These results show that the optimal TAS scheme has better OP performance than the suboptimal scheme. Further, the power allocation parameter has a significant influence on the OP performance. PMID- 26907283 TI - Characterization of Degradation Progressive in Composite Laminates Subjected to Thermal Fatigue and Moisture Diffusion by Lamb Waves. AB - Laminate composites which are widely used in the aeronautical industry, are usually subjected to frequency variation of environmental temperature and excessive humidity in the in-service environment. The thermal fatigue and moisture absorption in composites may induce material degradation. There is a demand to investigate the coupling damages mechanism and characterize the degradation evolution of composite laminates for the particular application. In this paper, the degradation evolution in unidirectional carbon/epoxy composite laminates subjected to thermal fatigue and moisture absorption is characterized by Lamb waves. The decrease rate of Lamb wave velocity is used to track the degradation evolution in the specimens. The results show that there are two stages for the progressive degradation of composites under the coupling effect of thermal cyclic loading and moisture diffusion. The present work provides an alternative to monitoring the degradation evolution of in-service aircraft composite Laminates. PMID- 26907284 TI - UAV-Based Estimation of Carbon Exports from Heterogeneous Soil Landscapes--A Case Study from the CarboZALF Experimental Area. AB - The advantages of remote sensing using Unmanned Aerial Vehicles (UAVs) are a high spatial resolution of images, temporal flexibility and narrow-band spectral data from different wavelengths domains. This enables the detection of spatio-temporal dynamics of environmental variables, like plant-related carbon dynamics in agricultural landscapes. In this paper, we quantify spatial patterns of fresh phytomass and related carbon (C) export using imagery captured by a 12-band multispectral camera mounted on the fixed wing UAV Carolo P360. The study was performed in 2014 at the experimental area CarboZALF-D in NE Germany. From radiometrically corrected and calibrated images of lucerne (Medicago sativa), the performance of four commonly used vegetation indices (VIs) was tested using band combinations of six near-infrared bands. The highest correlation between ground based measurements of fresh phytomass of lucerne and VIs was obtained for the Enhanced Vegetation Index (EVI) using near-infrared band b899. The resulting map was transformed into dry phytomass and finally upscaled to total C export by harvest. The observed spatial variability at field- and plot-scale could be attributed to small-scale soil heterogeneity in part. PMID- 26907285 TI - An Effective Collaborative Mobile Weighted Clustering Schemes for Energy Balancing in Wireless Sensor Networks. AB - Collaborative strategies for mobile sensor nodes ensure the efficiency and the robustness of data processing, while limiting the required communication bandwidth. In order to solve the problem of pipeline inspection and oil leakage monitoring, a collaborative weighted mobile sensing scheme is proposed. By adopting a weighted mobile sensing scheme, the adaptive collaborative clustering protocol can realize an even distribution of energy load among the mobile sensor nodes in each round, and make the best use of battery energy. A detailed theoretical analysis and experimental results revealed that the proposed protocol is an energy efficient collaborative strategy such that the sensor nodes can communicate with a fusion center and produce high power gain. PMID- 26907286 TI - Detection of Gold Nanoparticles Aggregation Growth Induced by Nucleic Acid through Laser Scanning Confocal Microscopy. AB - The gold nanoparticle (GNP) aggregation growth induced by deoxyribonucleic acid (DNA) is studied by laser scanning confocal and environmental scanning electron microscopies. As in the investigated case the direct light scattering analysis is not suitable, we observe the behavior of the fluorescence produced by a dye and we detect the aggregation by the shift and the broadening of the fluorescence peak. Results of laser scanning confocal microscopy images and the fluorescence emission spectra from lambda scan mode suggest, in fact, that the intruding of the hydrophobic moiety of the probe within the cationic surfactants bilayer film coating GNPs results in a Forster resonance energy transfer. The environmental scanning electron microscopy images show that DNA molecules act as template to assemble GNPs into three-dimensional structures which are reminiscent of the DNA helix. This study is useful to design better nanobiotechnological devices using GNPs and DNA. PMID- 26907287 TI - Technique for Determining Bridge Displacement Response Using MEMS Accelerometers. AB - In bridge maintenance, particularly with regard to fatigue damage in steel bridges, it is important to determine the displacement response of the entire bridge under a live load as well as that of each member. Knowing the displacement response enables the identification of dynamic deformations that can cause stresses and ultimately lead to damage and thus also allows the undertaking of appropriate countermeasures. In theory, the displacement response can be calculated from the double integration of the measured acceleration. However, data measured by an accelerometer include measurement errors caused by the limitations of the analog-to-digital conversion process and sensor noise. These errors distort the double integration results. Furthermore, as bridges in service are constantly vibrating because of passing vehicles, estimating the boundary conditions for the numerical integration is difficult. To address these problems, this paper proposes a method for determining the displacement of a bridge in service from its acceleration based on its free vibration. To verify the effectiveness of the proposed method, field measurements were conducted using nine different accelerometers. Based on the results of these measurements, the proposed method was found to be highly accurate in comparison with the reference displacement obtained using a contact displacement gauge. PMID- 26907288 TI - A Robust Camera-Based Interface for Mobile Entertainment. AB - Camera-based interfaces in mobile devices are starting to be used in games and apps, but few works have evaluated them in terms of usability or user perception. Due to the changing nature of mobile contexts, this evaluation requires extensive studies to consider the full spectrum of potential users and contexts. However, previous works usually evaluate these interfaces in controlled environments such as laboratory conditions, therefore, the findings cannot be generalized to real users and real contexts. In this work, we present a robust camera-based interface for mobile entertainment. The interface detects and tracks the user's head by processing the frames provided by the mobile device's front camera, and its position is then used to interact with the mobile apps. First, we evaluate the interface as a pointing device to study its accuracy, and different factors to configure such as the gain or the device's orientation, as well as the optimal target size for the interface. Second, we present an in the wild study to evaluate the usage and the user's perception when playing a game controlled by head motion. Finally, the game is published in an application store to make it available to a large number of potential users and contexts and we register usage data. Results show the feasibility of using this robust camera-based interface for mobile entertainment in different contexts and by different people. PMID- 26907289 TI - A Layered Approach for Robust Spatial Virtual Human Pose Reconstruction Using a Still Image. AB - Pedestrian detection and human pose estimation are instructive for reconstructing a three-dimensional scenario and for robot navigation, particularly when large amounts of vision data are captured using various data-recording techniques. Using an unrestricted capture scheme, which produces occlusions or breezing, the information describing each part of a human body and the relationship between each part or even different pedestrians must be present in a still image. Using this framework, a multi-layered, spatial, virtual, human pose reconstruction framework is presented in this study to recover any deficient information in planar images. In this framework, a hierarchical parts-based deep model is used to detect body parts by using the available restricted information in a still image and is then combined with spatial Markov random fields to re-estimate the accurate joint positions in the deep network. Then, the planar estimation results are mapped onto a virtual three-dimensional space using multiple constraints to recover any deficient spatial information. The proposed approach can be viewed as a general pre-processing method to guide the generation of continuous, three dimensional motion data. The experiment results of this study are used to describe the effectiveness and usability of the proposed approach. PMID- 26907290 TI - Sensitivity Enhancement in Magnetic Sensors Based on Ferroelectric-Bimorphs and Multiferroic Composites. AB - Multiferroic composites with ferromagnetic and ferroelectric phases have been studied in recent years for use as sensors of AC and DC magnetic fields. Their operation is based on magneto-electric (ME) coupling between the electric and magnetic subsystems and is mediated by mechanical strain. Such sensors for AC magnetic fields require a bias magnetic field to achieve pT-sensitivity. Novel magnetic sensors with a permanent magnet proof mass, either on a ferroelectric bimorph or a ferromagnetic-ferroelectric composite, are discussed. In both types, the interaction between the applied AC magnetic field and remnant magnetization of the magnet results in a mechanical strain and a voltage response in the ferroelectric. Our studies have been performed on sensors with a Nd-Fe-B permanent magnet proof mass on (i) a bimorph of oppositely-poled lead zirconate titanate (PZT) platelets and (ii) a layered multiferroic composite of PZT-Metglas Ni. The sensors have been characterized in terms of sensitivity and equivalent magnetic noise N. Noise N in both type of sensors is on the order of 200 pT/?Hz at 1 Hz, a factor of 10 improvement compared to multiferroic sensors without a proof mass. When the AC magnetic field is applied at the bending resonance for the bimorph, the measured N ~ 700 pT/?Hz. We discuss models based on magneto electro-mechanical coupling at low frequency and bending resonance in the sensors and theoretical estimates of ME voltage coefficients are in very good agreement with the data. PMID- 26907291 TI - Fast, Highly-Sensitive, and Wide-Dynamic-Range Interdigitated Capacitor Glucose Biosensor Using Solvatochromic Dye-Containing Sensing Membrane. AB - In this paper, we proposed an interdigitated capacitor (IDC)-based glucose biosensor to measure different concentrations of glucose from 1 MUM to 1 M. We studied four different types of solvatochromic dyes: Auramine O, Nile red, Rhodamine B, and Reichardt's dye (R-dye). These dyes were individually incorporated into a polymer [polyvinyl chloride (PVC)] and N,N-Dimethylacetamide (DMAC) solution to make the respective dielectric/sensing materials. To the best of our knowledge, we report for the first time an IDC glucose biosensing system utilizing a solvatochromic-dye-containing sensing membrane. These four dielectric or sensing materials were individually placed into the interdigitated electrode (IDE) by spin coating to make four IDC glucose biosensing elements. The proposed IDC glucose biosensor has a high sensing ability over a wide dynamic range and its sensitivity was about 23.32 mV/decade. It also has fast response and recovery times of approximately 7 s and 5 s, respectively, excellent reproducibility with a standard deviation of approximately 0.023, highly stable sensing performance, and real-time monitoring capabilities. The proposed IDC glucose biosensor was compared with an IDC, potentiometric, FET, and fiber-optic glucose sensor with respect to response time, dynamic range width, sensitivity, and linearity. We observed that the designed IDC glucose biosensor offered excellent performance. PMID- 26907292 TI - Thin Film Differential Photosensor for Reduction of Temperature Effects in Lab-on Chip Applications. AB - This paper presents a thin film structure suitable for low-level radiation measurements in lab-on-chip systems that are subject to thermal treatments of the analyte and/or to large temperature variations. The device is the series connection of two amorphous silicon/amorphous silicon carbide heterojunctions designed to perform differential current measurements. The two diodes experience the same temperature, while only one is exposed to the incident radiation. Under these conditions, temperature and light are the common and differential mode signals, respectively. A proper electrical connection reads the differential current of the two diodes (ideally the photocurrent) as the output signal. The experimental characterization shows the benefits of the differential structure in minimizing the temperature effects with respect to a single diode operation. In particular, when the temperature varies from 23 to 50 degrees C, the proposed device shows a common mode rejection ratio up to 24 dB and reduces of a factor of three the error in detecting very low-intensity light signals. PMID- 26907293 TI - CSRQ: Communication-Efficient Secure Range Queries in Two-Tiered Sensor Networks. AB - In recent years, we have seen many applications of secure query in two-tiered wireless sensor networks. Storage nodes are responsible for storing data from nearby sensor nodes and answering queries from Sink. It is critical to protect data security from a compromised storage node. In this paper, the Communication efficient Secure Range Query (CSRQ)-a privacy and integrity preserving range query protocol-is proposed to prevent attackers from gaining information of both data collected by sensor nodes and queries issued by Sink. To preserve privacy and integrity, in addition to employing the encoding mechanisms, a novel data structure called encrypted constraint chain is proposed, which embeds the information of integrity verification. Sink can use this encrypted constraint chain to verify the query result. The performance evaluation shows that CSRQ has lower communication cost than the current range query protocols. PMID- 26907294 TI - A Dual-Linear Kalman Filter for Real-Time Orientation Determination System Using Low-Cost MEMS Sensors. AB - To provide a long-time reliable orientation, sensor fusion technologies are widely used to integrate available inertial sensors for the low-cost orientation estimation. In this paper, a novel dual-linear Kalman filter was designed for a multi-sensor system integrating MEMS gyros, an accelerometer, and a magnetometer. The proposed filter precludes the impacts of magnetic disturbances on the pitch and roll which the heading is subjected to. The filter can achieve robust orientation estimation for different statistical models of the sensors. The root mean square errors (RMSE) of the estimated attitude angles are reduced by 30.6% under magnetic disturbances. Owing to the reduction of system complexity achieved by smaller matrix operations, the mean total time consumption is reduced by 23.8%. Meanwhile, the separated filter offers greater flexibility for the system configuration, as it is possible to switch on or off the second stage filter to include or exclude the magnetometer compensation for the heading. Online experiments were performed on the homemade miniature orientation determination system (MODS) with the turntable. The average RMSE of estimated orientation are less than 0.4 degrees and 1 degrees during the static and low-dynamic tests, respectively. More realistic tests on two-wheel self-balancing vehicle driving and indoor pedestrian walking were carried out to evaluate the performance of the designed MODS when high accelerations and angular rates were introduced. Test results demonstrate that the MODS is applicable for the orientation estimation under various dynamic conditions. This paper provides a feasible alternative for low-cost orientation determination. PMID- 26907295 TI - BlueDetect: An iBeacon-Enabled Scheme for Accurate and Energy-Efficient Indoor Outdoor Detection and Seamless Location-Based Service. AB - The location and contextual status (indoor or outdoor) is fundamental and critical information for upper-layer applications, such as activity recognition and location-based services (LBS) for individuals. In addition, optimizations of building management systems (BMS), such as the pre-cooling or heating process of the air-conditioning system according to the human traffic entering or exiting a building, can utilize the information, as well. The emerging mobile devices, which are equipped with various sensors, become a feasible and flexible platform to perform indoor-outdoor (IO) detection. However, power-hungry sensors, such as GPS and WiFi, should be used with caution due to the constrained battery storage on mobile device. We propose BlueDetect: an accurate, fast response and energy efficient scheme for IO detection and seamless LBS running on the mobile device based on the emerging low-power iBeacon technology. By leveraging the on-broad Bluetooth module and our proposed algorithms, BlueDetect provides a precise IO detection service that can turn on/off on-board power-hungry sensors smartly and automatically, optimize their performances and reduce the power consumption of mobile devices simultaneously. Moreover, seamless positioning and navigation services can be realized by it, especially in a semi-outdoor environment, which cannot be achieved by GPS or an indoor positioning system (IPS) easily. We prototype BlueDetect on Android mobile devices and evaluate its performance comprehensively. The experimental results have validated the superiority of BlueDetect in terms of IO detection accuracy, localization accuracy and energy consumption. PMID- 26907296 TI - Parametric Cognitive Modeling of Information and Computer Technology Usage by People with Aging- and Disability-Derived Functional Impairments. AB - Despite the speedy evolution of Information and Computer Technology (ICT), and the growing recognition of the importance of the concept of universal design in all domains of daily living, mainstream ICT-based product designers and developers still work without any truly structured tools, guidance or support to effectively adapt their products and services to users' real needs. This paper presents the approach used to define and evaluate parametric cognitive models that describe interaction and usage of ICT by people with aging- and disability derived functional impairments. A multisensorial training platform was used to train, based on real user measurements in real conditions, the virtual parameterized user models that act as subjects of the test-bed during all stages of simulated disabilities-friendly ICT-based products design. An analytical study was carried out to identify the relevant cognitive functions involved, together with their corresponding parameters as related to aging- and disability-derived functional impairments. Evaluation of the final cognitive virtual user models in a real application has confirmed that the use of these models produce concrete valuable benefits to the design and testing process of accessible ICT-based applications and services. Parameterization of cognitive virtual user models allows incorporating cognitive and perceptual aspects during the design process. PMID- 26907297 TI - An Attachable Electromagnetic Energy Harvester Driven Wireless Sensing System Demonstrating Milling-Processes and Cutter-Wear/Breakage-Condition Monitoring. AB - An attachable electromagnetic-energy-harvester driven wireless vibration-sensing system for monitoring milling-processes and cutter-wear/breakage-conditions is demonstrated. The system includes an electromagnetic energy harvester, three single-axis Micro Electro-Mechanical Systems (MEMS) accelerometers, a wireless chip module, and corresponding circuits. The harvester consisting of magnets with a coil uses electromagnetic induction to harness mechanical energy produced by the rotating spindle in milling processes and consequently convert the harnessed energy to electrical output. The electrical output is rectified by the rectification circuit to power the accelerometers and wireless chip module. The harvester, circuits, accelerometer, and wireless chip are integrated as an energy harvester driven wireless vibration-sensing system. Therefore, this completes a self-powered wireless vibration sensing system. For system testing, a numerical controlled machining tool with various milling processes is used. According to the test results, the system is fully self-powered and able to successfully sense vibration in the milling processes. Furthermore, by analyzing the vibration signals (i.e., through analyzing the electrical outputs of the accelerometers), criteria are successfully established for the system for real-time accurate simulations of the milling-processes and cutter-conditions (such as cutter-wear conditions and cutter-breaking occurrence). Due to these results, our approach can be applied to most milling and other machining machines in factories to realize more smart machining technologies. PMID- 26907298 TI - Investigation of the Performance of HEMT-Based NO, NO2 and NH3 Exhaust Gas Sensors for Automotive Antipollution Systems. AB - We report improved sensitivity to NO, NO2 and NH3 gas with specially-designed AlGaN/GaN high electron mobility transistors (HEMT) that are suitable for operation in the harsh environment of diesel exhaust systems. The gate of the HEMT device is functionalized using a Pt catalyst for gas detection. We found that the performance of the sensors is enhanced at a temperature of 600 degrees C, and the measured sensitivity to 900 ppm-NO, 900 ppm-NO2 and 15 ppm-NH3 is 24%, 38.5% and 33%, respectively, at 600 degrees C. We also report dynamic response times as fast as 1 s for these three gases. Together, these results indicate that HEMT sensors could be used in a harsh environment with the ability to control an anti-pollution system in real time. PMID- 26907300 TI - Design of New Power Management Circuit for Light Energy Harvesting System. AB - Nowadays, it can be observed that Wireless Sensors Networks (WSN) are taking increasingly vital roles in many applications, such as building energy monitoring and control, which is the focus of the work in this paper. However, the main challenging issue with adopting WSN technology is the use of power sources such as batteries, which have a limited lifetime. A smart solution that could tackle this problem is using Energy Harvesting technology. The work in this paper will be focused on proposing a new power management design through harvesting indoor light intensity. The new approach is inspired by the use of the Fractional Open Circuit Voltage based Maximum Power Point tracking (MPPT) concept for sub mw Photo Voltaic (PV) cells. The new design adopts two main features: First, it minimizes the power consumed by the power management section; and second, it maximizes the MPPT-converted output voltage and consequently improves the efficiency of the power conversion in the sub mw power level. The new experimentally-tested design showed an improvement of 81% in the efficiency of MPPT conversion using 0.5 mW input power in comparison with the other presented solutions that showed less efficiency with higher input power. PMID- 26907299 TI - Molecularly Imprinted Electropolymer for a Hexameric Heme Protein with Direct Electron Transfer and Peroxide Electrocatalysis. AB - For the first time a molecularly imprinted polymer (MIP) with direct electron transfer (DET) and bioelectrocatalytic activity of the target protein is presented. Thin films of MIPs for the recognition of a hexameric tyrosine coordinated heme protein (HTHP) have been prepared by electropolymerization of scopoletin after oriented assembly of HTHP on a self-assembled monolayer (SAM) of mercaptoundecanoic acid (MUA) on gold electrodes. Cavities which should resemble the shape and size of HTHP were formed by template removal. Rebinding of the target protein sums up the recognition by non-covalent interactions between the protein and the MIP with the electrostatic attraction of the protein by the SAM. HTHP bound to the MIP exhibits quasi-reversible DET which is reflected by a pair of well pronounced redox peaks in the cyclic voltammograms (CVs) with a formal potential of -184.4 +/- 13.7 mV vs. Ag/AgCl (1 M KCl) at pH 8.0 and it was able to catalyze the cathodic reduction of peroxide. At saturation the MIP films show a 12-fold higher electroactive surface concentration of HTHP than the non imprinted polymer (NIP). PMID- 26907301 TI - Fast 2D DOA Estimation Algorithm by an Array Manifold Matching Method with Parallel Linear Arrays. AB - In this paper, the problem of two-dimensional (2D) direction-of-arrival (DOA) estimation with parallel linear arrays is addressed. Two array manifold matching (AMM) approaches, in this work, are developed for the incoherent and coherent signals, respectively. The proposed AMM methods estimate the azimuth angle only with the assumption that the elevation angles are known or estimated. The proposed methods are time efficient since they do not require eigenvalue decomposition (EVD) or peak searching. In addition, the complexity analysis shows the proposed AMM approaches have lower computational complexity than many current state-of-the-art algorithms. The estimated azimuth angles produced by the AMM approaches are automatically paired with the elevation angles. More importantly, for estimating the azimuth angles of coherent signals, the aperture loss issue is avoided since a decorrelation procedure is not required for the proposed AMM method. Numerical studies demonstrate the effectiveness of the proposed approaches. PMID- 26907302 TI - Bisdioxycalamenene: A Bis-Sesquiterpene from the Soft Coral Rhytisma fulvum fulvum. AB - A dichloromethane extract of the soft coral Rhytisma fulvum fulvum collected in Madagascar afforded a novel compound possessing an unprecedented pentacyclic skeleton, bisdioxycalamenene (1), as well as seven known sesquiterpenes. The structures of the compounds were elucidated using 1D and 2D NMR techniques, as well as high-resolution mass spectrometry. The absolute configuration of 1 was determined using X-ray diffraction analysis and anomalous dispersion effects. The structure elucidation and a possible biogenesis of the compound are discussed. PMID- 26907304 TI - Production and Characterization of Antioxidant Properties of Exopolysaccharide(s) from Peanibacillus mucilaginosus TKU032. AB - Natural polysaccharides have received much attention due to their wide range of applications. Although most microbial exopolysaccharides (EPSs) use sugars as the major carbon source, such as glucose or sucrose, in this study, EPSs were induced from a squid pen powder (SPP)-containing medium by Paenibacillus mucilaginosus TKU032, a bacterial strain isolated from Taiwanese soil. Under the optimal culture conditions, the maximum EPS yield (14.8 g/L) was obtained. MALDI-TOF MS analysis of an EPS fraction purified by gel filtration revealed two mass peaks with molecular weights of ~1.05 * 104 and ~1.35 * 104 Da, respectively. The analysis of the hydrolysates of TKU032 EPS with cellulase, pectinase or alpha amylase indicated that the glycosidic bond of TKU032 EPS is most likely an alpha 1,4 glycosidic bond and the hydrolysates are similar to those of starch. In addition, the purified EPS demonstrated strong antioxidant abilities. PMID- 26907303 TI - Chemical Diversity and Biological Properties of Secondary Metabolites from Sea Hares of Aplysia Genus. AB - The marine environment is an important source of structurally-diverse and biologically-active secondary metabolites. During the last two decades, thousands of compounds were discovered in marine organisms, several of them having inspired the development of new classes of therapeutic agents. Marine mollusks constitute a successful phyla in the discovery of new marine natural products (MNPs). Over a 50-year period from 1963, 116 genera of mollusks contributed innumerous compounds, Aplysia being the most studied genus by MNP chemists. This genus includes 36 valid species and should be distinguished from all mollusks as it yielded numerous new natural products. Aplysia sea hares are herbivorous mollusks, which have been proven to be a rich source of secondary metabolites, mostly of dietary origin. The majority of secondary metabolites isolated from sea hares of the genus Aplysia are halogenated terpenes; however, these animals are also a source of compounds from other chemical classes, such as macrolides, sterols and alkaloids, often exhibiting cytotoxic, antibacterial, antifungal, antiviral and/or antifeedant activities. This review focuses on the diverse structural classes of secondary metabolites found in Aplysia spp., including several compounds with pronounced biological properties. PMID- 26907306 TI - The Emergence and Challenging Growth of the Bio-Ethanol Innovation System in Taiwan (1949-2015). AB - This study explores the bio-ethanol innovation system in Taiwan from the perspective of a technology innovation system (TIS). Taiwan is a newly industrialized country and is not currently a main producer of bio-ethanol. This study analyzes the evolution of bio-ethanol innovation system in Taiwan and places a particular emphasis on challenges that present policies face in the context of potential long-term bio-ethanol development. Through an evaluation of the consistency of the present research, technology, development and innovation (RTDI) policies as well as the influence of these policies on the functional dynamics of bio-ethanol innovation system, mechanisms prohibiting the system from flourishing are determined. It is suggested that the production of bio-ethanol in Taiwan would be achieved if the government: (1) fixes long-term targets for both domestic bio-ethanol development and emission reduction; and (2) comprehensively designs a set of interrelated RTDI policies in accordance with the functional pattern of the bio-ethanol innovation system and consistently implements these policies. If such measures were implemented, it is considered that the bio ethanol innovation system in Taiwan would flourish. PMID- 26907305 TI - Protective Effect of Onion Extract on Bleomycin-Induced Cytotoxicity and Genotoxicity in Human Lymphocytes. AB - Following one of the world's largest nuclear accidents, occured at Fukushima, Japan in 2011, a significant scientific effort has focused on minimizing the potential adverse health effects due to radiation exposure. The use of natural dietary antioxidants to reduce the risk of radiation-induced oxidative DNA damage is a simple strategy for minimizing radiation-related cancer rates and improving overall health. The onion is among the richest sources of dietary flavonoids and is an important food for increasing their overall intake. Therefore, we examined the effect of an onion extract on cyto- and geno-toxicity in human lymphocytes treated with bleomycin (BLM), a radiomimetic agent. In addition, we measured the frequency of micronuclei (MN) and DNA damage following treatment with BLM using a cytokinesis-blocked micronucleus assay and a single cell gel electrophoresis assay. We observed a significant increase in cell viability in lymphocytes treated with onion extract then exposed to BLM compared to cells treated with BLM alone. The frequency of BLM induced MN and DNA damage increased in a dose dependent manner; however, when lymphocytes were pretreated with onion extract (10 and 20 MUL/mL), the frequency of BLM-induced MN was decreased at all doses of BLM and DNA damage was decreased at 3 MUg/mL of BLM. These results suggest that onion extract may have protective effects against BLM-induced cyto- and genotoxicity in human lymphocytes. PMID- 26907307 TI - Determination of Sediment Oxygen Demand in the Ziya River Watershed, China: Based on Laboratory Core Incubation and Microelectrode Measurements. AB - A study coupling sedimentcore incubation and microelectrode measurement was performed to explore the sediment oxygen demand (SOD) at 16 stations in the Ziya River Watershed, a severely polluted and anoxic river system in the north of China. Total oxygen flux values in the range 0.19-1.41 g/(m2.d) with an average of 0.62 g/(m2.d) were obtained by core incubations, and diffusive oxygen flux values in the range 0.15-1.38 g/(m2.d) with an average of 0.51 g/(m2.d) were determined by microelectrodes. Total oxygen flux obviously correlated with diffusive oxygen flux (R2 = 0.842). The microelectrode method produced smaller results than the incubation method in 15 of 16 sites, and the diffusive oxygen flux was smaller than the total oxygen flux. Although the two sets of SOD values had significant difference accepted by the two methods via the Wilcoxon signed rank test (p < 0.05), the microelectrode method was shown to produce results that were similar to those from the core incubation method. The microelectrode method, therefore, could be used as an alternative method for traditional core incubation method, or as a method to verify SOD rates measured by other methods. We consider that high potential sediment oxygen demand would occur in the Ziya River Watershed when the dissolved oxygen (DO) recovered in the overlying water. PMID- 26907308 TI - Sunbed Use Prevalence and Associated Skin Health Habits: Results of a Representative, Population-Based Survey among Austrian Residents. AB - Recreational sunbed use accounts for the main non-solar source of exposure to ultraviolet radiation in fair-skinned Western populations. Indoor tanning is associated with increased risks for acute and chronic dermatological diseases. The current community-based study assessed the one-year prevalence of sunbed use and associated skin health habits among a representative, gender-balanced sample of 1500 Austrian citizens. Overall one-year prevalence of sunbed use was 8.9% (95% confidence interval (CI) 7.5%-10.4%), with slightly higher prevalence in females (9.2%, 95% CI 7.3%-11.2%) compared to males (8.6%, 95% CI 6.7%-10.6%). Factors predicting sunbed use were younger age (by trend decreasing with older age), place of living, smoking, skin type (by trend increasing with darker skin), sun exposure, motives to tan, and use of UV-free tanning products. Despite media campaigns on the harmful effects of excessive sunlight and sunbed exposure, we found a high prevalence of self-reported sunbed use among Austrian citizens. From a Public (Skin) Health perspective, the current research extends the understanding of prevailing leisure time skin health habits in adding data on prevalence of sunbed use in the general Austrian population. PMID- 26907310 TI - Distributions, Early Diagenesis, and Spatial Characteristics of Amino Acids in Sediments of Multi-Polluted Rivers: A Case Study in the Haihe River Basin, China. AB - The Haihe River Basin, which is one of the most water-scarce and polluted river basins in China, has abnormally high nitrogen levels. In this study, total hydrolyzable amino acids (THAAs) were measured in surface sediment and sediment core samples in the Haihe River Basin to determine if amino acids were potential sources of ammonium, organic nitrogen, and organic carbon. The rivers were found to be in a state of hypoxia and contain abnormally high levels of ammonium and organic nitrogen. Additionally, NH3-N was the predominant form of inorganic nitrogen in the surface sediments, while organic nitrogen accounted for 92.53% of sedimentary nitrogen. THAAs-C accounted for 14.92% of the total organic carbon, while THAAs-N accounted for more than 49.59% of organic nitrogen and 45.68% of total nitrogen. The major fraction of THAAs were protein amino acids. Three sediment cores of the most heavily polluted rivers also showed high levels of THAAs. Evaluation of the degradation index (DI) of sedimentary organic matter in sediments evaluated based on the THAAs revealed that most positive DI values were found in the downstream portion of the Ziya River Watershed. Additionally, the DI of surface sediment was correlated with THAAs (r2 = 0.763, p < 0.001), as was the DI of sediment cores (r2 = 0.773, p < 0.001). Overall, amino acids in sediments were found to be an important potential source of ammonium, organic nitrogen, and organic carbon. PMID- 26907309 TI - Disparities in Hypertension Prevalence, Awareness, Treatment and Control between Bouyei and Han: Results from a Bi-Ethnic Health Survey in Developing Regions from South China. AB - Hypertension is highly prevalent in low-income population. This study aims to investigate ethnic disparities in hypertension and identify modifiable factors related to its occurrence and control in developing regions in South China. Blood pressure was measured in the Bouyei and Han populations during a community-based health survey in Guizhou, 2012. A multistage stratified sampling method was adopted to recruit Bouyei and Han aged from 20 to 80 years. Taking mixed effects into consideration, multilevel logistic models with random intercept were used for data analysis. The prevalence rates of hypertension were 35.3% for the Bouyei and 33.7% for the Han. Among the hypertensive participants, 30.1% of the Bouyei and 40.2% of the Han were aware of their hypertensive conditions, 19.7% of the Bouyei and 31.1% of the Han were receiving treatment, and only 3.6% of the Bouyei and 9.9% of the Han had their blood pressure under control. Age-sex standardized rates of awareness, treatment, and control were consistently lower in the Bouyei than the Han. Such ethnic disparities were more evident in the elderly population. Avoidance of excessive alcohol consumption and better education were favorable lifestyle for reduction in risk of hypertension. Moderate physical activity improved control of hypertension in Bouyei patients under treatment. Conclusively, hypertension awareness, treatment, and control were substantially lower in Bouyei than Han, particularly in the elderly population. Such ethnic disparities indicate that elderly Bouyei population should be targeted for tailored interventions in the future. PMID- 26907311 TI - Leg Power As an Indicator of Risk of Injury or Illness in Police Recruits. AB - Tactical trainees, like those entering the police force, are required to undergo vigorous training as part of their occupational preparation. This training has the potential to cause injuries. In addition, the physical training, communal living and pressures of tactical training are known to induce immune suppression and have the potential to increase the risk of illness. The aim of this study was to investigate the relationship between leg power, as measured by a vertical jump (VJ), and rates of reported injuries and illnesses during police recruit training. Retrospective data from recruits (n = 1021) undergoing basic police recruit training at an Australian Police Force College was collected. Recruits completed a VJ assessment at the commencement of their second state of training. Formally reported illness and injuries were collected 12 weeks later, following completion of training. Correlations between VJ height and rates of reported illness and injury were low (r = -0.16 and -0.09, respectively) but significant (p < 0.005), with VJ height accounting for 2.6% and 0.8% of the variance in illness and injury rates, respectively. In terms of relative risks, recruits with the lowest recorded VJ heights were more than three times as likely as those with highest VJ heights to suffer injury and/or illness. Police recruits with lower VJ height are at a significantly greater risk of suffering an injury or illness during police basic recruit training. PMID- 26907312 TI - Appropriate LDL-C-to-HDL-C Ratio Cutoffs for Categorization of Cardiovascular Disease Risk Factors among Uygur Adults in Xinjiang, China. AB - Elevated LDL-C/HDL-C ratio has been shown to be a marker of lipid metabolism as well as a good predictor of coronary artery disease (CAD). Thus, the aim of this study was to investigate whether the LDL-C/HDL-C ratio is useful for detecting cardiovascular disease (CVD) risk factors in general healthy Uygur adults in Xinjiang. A total of 4047 Uygur subjects aged >=35 years were selected from the Cardiovascular Risk Survey (CRS) study which was carried out from October 2007 to March 2010. Anthropometric data, blood pressure, lipid profile and fasting glucose were measured in all participants. The prevalence, sensitivity, specificity and distance on the receiver operating characteristic (ROC) curve of each LDL-C/HDL-C ratio were calculated. The prevalence of high LDL-C and low HDL C cholesterol was high and positively correlated with higher LDL-C/HDL-C ratio in the Uygur population. In both men and women, we detected a slight apparent trend of high prevalence of hypertension and hypercholesterolemia with higher LDL-C/HDL C ratio. Our study also demonstrated that the discriminatory power of the LDL C/HDL-C ratio for CVD risk factors was slightly stronger in men than in women. Analysis of the shortest distance in the ROC curves for hypertension, dyslipidemia, diabetes, or >=two of these risk factors suggested a LDL-C/HDL-C ratio cutoff of 2.5 for both men and women. The results of this study showed that a LDL-C/HDL-C ratio cut-off of 2.5 might be used as the predictive marker to detect CVD risk factors among Uygur adults in Xinjiang. PMID- 26907313 TI - Vulnerability of Coastal Communities from Storm Surge and Flood Disasters. AB - Disasters in the form of coastal storms and hurricanes can be very destructive. Preparing for anticipated effects of such disasters can help reduce the public health and economic burden. Identifying vulnerable population groups can help prioritize resources for the most needed communities. This paper presents a quantitative framework for vulnerability measurement that incorporates both socioeconomic and flood inundation vulnerability. The approach is demonstrated for three coastal communities in Mississippi with census tracts being the study unit. The vulnerability results are illustrated as thematic maps for easy usage by planners and emergency responders to assist in prioritizing their actions to vulnerable populations during storm surge and flood disasters. PMID- 26907314 TI - Sex and Age Differences in Exposure to Secondhand Smoke at Home among Korean Adolescents: A Nationally Representative Survey. AB - The authors assessed sex and age differences in secondhand smoke (SHS) exposure among vulnerable adolescent populations. Data from the 2013 Korea Youth Risk Behavior Web-based Survey of 64,499 non-smokers aged 13-18 years were analyzed using multiple logistic regression. Girls were exposed 1.26 times (95% confidence interval, 1.21-1.32) more to home SHS than boys, and the younger adolescents were more likely to be exposed to home SHS than were the older, regardless of sex (p < 0.001). Younger girls living with or without current smokers and the younger boys living with current smokers were more likely to be exposed to SHS at home, when the data were stratified according to current household member smoking, which was one of the main risk factors for SHS exposure at home. Girls living with current smokers were more likely to be exposed to SHS at home than boys regardless age. Girls and younger adolescents, populations vulnerable to smoke exposure, were more likely to be exposed to SHS at home, even though they should be more protected. It is necessary to improve home SHS awareness, especially among these vulnerable populations. PMID- 26907315 TI - E-Cigarette as a Harm Reduction Approach among Tobacco Smoking Khat Chewers: A Promising Bullet of Multiple Gains. AB - Khat chewing/use, a green leaf with amphetamine-like effects is socially integrated in the Middle East and Africa. Khat chewing is often associated with tobacco smoking and occurs in closed places, such as a family home setting where the smoke-free laws cannot be implemented. Tobacco cigarette smoking among khat chewers is a significant concern, but there is also second-hand exposure to smoke at home or in places where khat users gather. Evidence suggests that e-cigarettes represent a significantly less harmful form of nicotine intake. Evaluating the effects of e-cigarettes among khat chewers could be important in understanding the impact of e-cigarettes as a harm reduction approach, with the potential to reduce the health risk associated with smoking. PMID- 26907316 TI - Prevalence of Heart Failure and Adherence to Process Indicators: Which Socio Demographic Determinants are Involved? AB - Interest in chronic conditions reflects their role as the first cause of death and disability in developed countries; improving the management of these conditions is a priority for health care services. The aim of this study was to establish which sociodemographic factors influence adherence to standards of care for chronic heart failure (CHF). A generalized multilevel structural equation model was developed and applied to a sample of patients with CHF obtained from administrative data flows in six Italian regions to ascertain any associations between adherence to standards of care for CHF and sociodemographic variables. Indicators of compliance were adherence to beta-blocker therapy (BB-A) and Angiotensin Convertin Enzime inhibitor/Angiotensin Receptor Blocker therapy (ACE A), and creatinine and electrolyte testing (CNK-T). All indicators were computed over a one-year follow-up. Among a cohort of 24,997 patients, the BB-A rate was 40.4%, the ACE-A rate 61.1%, and the CNK-T rate 57.0%. Factors found associated with adherence were gender, age, and citizenship. Our study shows an inadequate adherence to standards of care for CHF, particularly associated with certain sociodemographic characteristics. This suggests the need to improve the role of primary care in managing this chronic condition. The measures considered only apply to patients with a reduced Left Ventricular Ejection Fraction, hence a limitation of this analysis is the lack of information on left ventricular ejection. PMID- 26907317 TI - Use of a Robotic Sampler (PIPER) for Evaluation of Particulate Matter Exposure and Eczema in Preschoolers. AB - While the association of eczema with asthma is well recognized, little research has focused on the potential role of inhalable exposures and eczema. While indoor air quality is important in the development of respiratory disease as children in the U.S. spend the majority of their time indoors, relatively little research has focused on correlated non-respiratory conditions. This study examined the relationship between particulate matter (PM) exposures in preschool age children and major correlates of asthma, such as wheeze and eczema. Air sampling was carried out using a robotic (PIPER) child-sampling surrogate. This study enrolled 128 participants, 57 male and 71 female children. Ages ranged from 3 to 58 months with the mean age of 29.3 months. A comparison of subjects with and without eczema showed a difference in the natural log (ln) of PM collected from the PIPER air sampling (p = 0.049). PIPER's sampling observed an association between the ln PM concentrations and eczema, but not an association with wheezing history in pre school children. Our findings are consistent with the hypothesis of the role of the microenvironment in mediating atopic dermatitis, which is one of the predictors of persistent asthma. Our findings also support the use of PIPER in its ability to model and sample the microenvironment of young children. PMID- 26907318 TI - Characteristics and Outcomes of Patients Injured in Road Traffic Crashes and Transported by Emergency Medical Services. AB - To investigate the injury characteristics and mortality of patients transported by emergency medical services (EMS) and hospitalized for trauma following a road traffic crash, data obtained from the Trauma Registry System were retrospectively reviewed for trauma admissions between 1 January 2009 and 31 December 2013 in a Level I trauma center. Of 16,548 registered patients, 3978 and 1440 patients injured in road traffic crashes were transported to the emergency department by EMS and non-EMS, respectively. Patients transported by EMS had lower Glasgow coma scale (GCS) scores and worse hemodynamic measures. Compared to patients transported by non-EMS, more patients transported by EMS required procedures (intubation, chest tube insertion, and blood transfusion) at the emergency department. They also sustained a higher injury severity, as measured by the injury severity score (ISS) and the new injury severity score (NISS). Lastly, in hospital mortality was higher among the EMS than the non-EMS group (1.8% vs. 0.3%, respectively; p < 0.001). However, we found no statistically significant difference in the adjusted odds ratio (AOR) for mortality among patients transported by EMS after adjustment for ISS (AOR 4.9, 95% CI 0.33-2.26), indicating that the higher incidence of mortality was likely attributed to the patients' higher injury severity. In addition, after propensity score matching, logistic regression of 58 well-matched pairs did not show a significant influence of transportation by EMS on mortality (OR: 0.578, 95% CI: 0.132-2.541 p = 0.468). PMID- 26907319 TI - Impact of Dust from Ore Processing Facilities on Rain Water Collection Tanks in a Tropical Environment--The Obvious Source "Ain't Necessarily So". AB - Concerns have been expressed that dust from the minerals processing facilities at Karumba Queensland Australia have resulted in elevated lead (Pb) concentrations in rain water tanks. The ores derived from the Century mine some 304 km from the port. High precision Pb isotopic measurements on environmental samples have been undertaken to evaluate the source of Pb in rainwaters and acid digests from roof wipes and gutter wipes. There does not appear to be any relationship between sample location and the processing facility but samples from the area subject to the prevailing winds show the highest contribution of Century Pb. All gutter wipes (82 to 1270 ug Pb/wipe) have contributions of Century ore ranging from 87% to 96%. The contribution of Century ore to five roof wipes (22 to 88 ug Pb/wipe) ranges from 89% to 97% and in the other two samples there is a mix of Century and Broken Hill Pb. Three of the seven rainwater have contributions of Century ore Pb ranging from 33% to 75%. Two of the other four rainwater samples have the highest water Pb concentrations of 88 and 100 ug/L and their isotopic data show Broken Hill Pb contributions ranging from 77% to 80%. The source of the Broken Hill Pb is probably from the galvanized roofing material and/or brass fittings in the rainwater tanks. The discrimination between various sources is only detectable using high precision (204)Pb-based isotopic ratios and not the now common inductively coupled plasma mass spectrometry (ICP-MS ) data presentations of the higher abundance isotopes (208)Pb, (207)Pb and (206)Pb. Isotopic results for the waters demonstrate that apportioning blame where there is an obvious point source may not always be the correct conclusion. Nevertheless the isotopic data for the gutter wipes indicates that there was widespread contamination from the processing facilities throughout the town. PMID- 26907320 TI - Assessment of Burden of Malaria in Gwanda District, Zimbabwe, Using the Disability Adjusted Life Years. AB - Malaria is one of the highest contributors to morbidity and mortality in Zimbabwe. However, there is paucity of knowledge regarding disability adjusted life years (DALYs) as a measure of burden of malaria in affected communities. The DALYs metric was used to assess the burden of malaria in Gwanda District with the aim of contributing to a better understanding of the impact of disease on affected communities. Data was collected from health facility malaria registers and the District Health Information System (DHIS) to estimate DALYs at household and district levels respectively. The household DALYs included 130 malaria cases from 2013 to 2015 while the DALYs for the district included 719 confirmed malaria cases from 2011 to 2015. Households lost a total of 153.89 DALYs with the majority of the disease burden (65.55%) occurring in the most economically productive age group (15-45 years) with a mean loss of 1.18 DALYs per malaria case. At district level, 251.09 DALYs were lost due to malaria and the calculated average district DALY rate for 2011-2015 was 36.29 DALYs/100,000 persons per year. It is important to estimate malaria burden to assist policy makers in making informed decisions when channelling resources for control and prevention of the disease. PMID- 26907321 TI - Effects of in Utero Exposure to Dicyclohexyl Phthalate on Rat Fetal Leydig Cells. AB - Dicyclohexyl phthalate (DCHP) is one of the phthalate plasticizers. The objective of the present study was to investigate the effects of DCHP on fetal Leydig cell distribution and function as well as testis development. Female pregnant Sprague Dawley dams orally received vehicle (corn oil, control) or DCHP (10, 100, and 500 mg/kg/day) from gestational day (GD) 12 to GD 21. At GD 21.5, testicular testosterone production, fetal Leydig cell number and distribution, testicular gene and protein expression levels were examined. DCHP administration produced a dose-dependent increase of the incidence of multinucleated gonocytes at >= 100 mg/kg. DCHP dose-dependently increased abnormal fetal Leydig cell aggregation and decreased fetal Leydig cell size, cytoplasmic size, and nuclear size at >= 10 mg/kg. DCHP reduced the expression levels of steroidogenesis-related genes (including Star, Hsd3b1, and Hsd17b3) and testis-descent related gene Insl3 as well as protein levels of 3beta-hydroxysteroid dehydrogenase 1 (HSD3B1) and insulin-like 3 (INSL3) at >= 10 mg/kg. DCHP significantly inhibited testicular testosterone levels at >= 100 mg/kg. The results indicate that in utero exposure to DCHP affects the expression levels of fetal Leydig cell steroidogenic genes and results in the occurrence of multinucleated gonocytes and Leydig cell aggregation. PMID- 26907322 TI - Heavy Metals in Surface Soils in the Upper Reaches of the Heihe River, Northeastern Tibetan Plateau, China. AB - The upper reaches of the Heihe River have been regarded as a hotspot for phytoecology, climate change, water resources and hydrology studies. Due to the cold-arid climate, high elevation, remote location and poor traffic conditions, few studies focused on heavy metal contamination of soils have been conducted or reported in this region. In the present study, an investigation was performed to provide information regarding the concentration levels, sources, spatial distributions, and environmental risks of heavy metals in this area for the first time. Fifty-six surface soil samples collected from the study area were analyzed for Cr, Mn, Ni, Cu, Zn, As, Cd and Pb concentrations, as well as TOC levels. Basic statistics, concentration comparisons, correlation coefficient analysis and multivariate analyses coupled with spatial distributions were utilized to delineate the features and the sources of different heavy metals. Risk assessments, including geoaccumulation index, enrichment factor and potential ecological risk index, were also performed. The results indicate that the concentrations of heavy metals have been increasing since the 1990 s. The mean values of each metal are all above the average background values in the Qinghai Province, Tibet, China and the world, except for that of Cr. Of special note is the concentration of Cd, which is extremely elevated compared with all background values. The distinguished ore-forming conditions and well-preserved, widely distributed limestones likely contribute to the high Cd concentration. Heavy metals in surface soils in the study area are primarily inherited from parent materials. Nonetheless, anthropogenic activities may have accelerated the process of weathering. Cd presents a high background concentration level and poses a severe environmental risk throughout the whole region. Soils in Yinda, Reshui daban, Kekeli and Zamasheng in particular pose threats to the health of the local population, as well as that of livestock and wildlife. PMID- 26907323 TI - Structural Proteomics of Herpesviruses. AB - Herpesviruses are highly prevalent viruses associated with numerous pathologies both in animal and human populations. Until now, most of the strategies used to prevent or to cure these infections have been unsuccessful because these viruses have developed numerous immune evasion mechanisms. Therefore, a better understanding of their complex lifecycle is needed. In particular, while the genome of numerous herpesviruses has been sequenced, the exact composition of virions remains unknown for most of them. Mass spectrometry has recently emerged as a central method and has permitted fundamental discoveries in virology. Here, we review mass spectrometry-based approaches that have recently allowed a better understanding of the composition of the herpesvirus virion. In particular, we describe strategies commonly used for proper sample preparation and fractionation to allow protein localization inside the particle but also to avoid contamination by nonstructural proteins. A collection of other important data regarding post translational modifications or the relative abundance of structural proteins is also described. This review also discusses the poorly studied importance of host proteins in herpesvirus structural proteins and the necessity to develop a quantitative workflow to better understand the dynamics of the structural proteome. In the future, we hope that this collaborative effort will assist in the development of new strategies to fight these infections. PMID- 26907324 TI - Infectious Mononucleosis Triggers Generation of IgG Auto-Antibodies against Native Myelin Oligodendrocyte Glycoprotein. AB - A history of infectious mononucleosis (IM), symptomatic primary infection with the Epstein Barr virus, is associated with the development of autoimmune diseases and increases the risk to develop multiple sclerosis. Here, we hypothesized that immune activation during IM triggers autoreactive immune responses. Antibody responses towards cellular antigens using a HEp-2 based indirect immunofluorescence assay and native myelin oligodendrocyte glycoprotein (MOG) using a flow cytometry-based assay were determined in 35 patients with IM and in 23 control subjects. We detected frequent immunoglobulin M (IgM) reactivity to vimentin, a major constituent of the intermediate filament family of proteins, in IM patients (27/35; 77%) but rarely in control subjects (2/23; 9%). IgG autoantibodies binding to HEp-2 cells were absent in both groups. In contrast, IgG responses to native MOG, present in up to 40% of children with inflammatory demyelinating diseases of the central nervous system (CNS), were detectable in 7/35 (20%) patients with IM but not in control subjects. Normalization of anti vimentin IgM levels to increased total IgM concentrations during IM resulted in loss of significant differences for anti-vimentin IgM titers. Anti-MOG specific IgG responses were still detectable in a subset of three out of 35 patients with IM (9%), even after normalization to increased total IgG levels. Vimentin specific IgM and MOG-specific IgG responses decreased following clinical resolution of acute IM symptoms. We conclude from our data that MOG-specific memory B cells are activated in subset of patients with IM. PMID- 26907325 TI - In Vitro and in Vivo Evaluation of Mutations in the NS Region of Lineage 2 West Nile Virus Associated with Neuroinvasiveness in a Mammalian Model. AB - West Nile virus (WNV) strains may differ significantly in neuroinvasiveness in vertebrate hosts. In contrast to genetic lineage 1 WNVs, molecular determinants of pathogenic lineage 2 strains have not been experimentally confirmed so far. A full-length infectious clone of a neurovirulent WNV lineage 2 strain (578/10; Central Europe) was generated and amino acid substitutions that have been shown to attenuate lineage 1 WNVs were introduced into the nonstructural proteins (NS1 (P250L), NS2A (A30P), NS3 (P249H) NS4B (P38G, C102S, E249G)). The mouse neuroinvasive phenotype of each mutant virus was examined following intraperitoneal inoculation of C57BL/6 mice. Only the NS1-P250L mutation was associated with a significant attenuation of virulence in mice compared to the wild-type. Multiplication kinetics in cell culture revealed significantly lower infectious virus titres for the NS1 mutant compared to the wild-type, as well as significantly lower amounts of positive and negative stranded RNA. PMID- 26907326 TI - Identification of Known and Novel Recurrent Viral Sequences in Data from Multiple Patients and Multiple Cancers. AB - Virus discovery from high throughput sequencing data often follows a bottom-up approach where taxonomic annotation takes place prior to association to disease. Albeit effective in some cases, the approach fails to detect novel pathogens and remote variants not present in reference databases. We have developed a species independent pipeline that utilises sequence clustering for the identification of nucleotide sequences that co-occur across multiple sequencing data instances. We applied the workflow to 686 sequencing libraries from 252 cancer samples of different cancer and tissue types, 32 non-template controls, and 24 test samples. Recurrent sequences were statistically associated to biological, methodological or technical features with the aim to identify novel pathogens or plausible contaminants that may associate to a particular kit or method. We provide examples of identified inhabitants of the healthy tissue flora as well as experimental contaminants. Unmapped sequences that co-occur with high statistical significance potentially represent the unknown sequence space where novel pathogens can be identified. PMID- 26907327 TI - A Toolbox for Herpesvirus miRNA Research: Construction of a Complete Set of KSHV miRNA Deletion Mutants. AB - Kaposi's sarcoma-associated herpesvirus (KSHV) encodes 12 viral microRNAs (miRNAs) that are expressed during latency. Research into KSHV miRNA function has suffered from a lack of genetic systems to study viral miRNA mutations in the context of the viral genome. We used the Escherichia coli Red recombination system together with a new bacmid background, BAC16, to create mutants for all known KSHV miRNAs. The specific miRNA deletions or mutations and the integrity of the bacmids have been strictly quality controlled using PCR, restriction digestion, and sequencing. In addition, stable viral producer cell lines based on iSLK cells have been created for wildtype KSHV, for 12 individual miRNA knock-out mutants (DeltamiR-K12-1 through -12), and for mutants deleted for 10 of 12 (DeltamiR-cluster) or all 12 miRNAs (DeltamiR-all). NGS, in combination with SureSelect technology, was employed to sequence the entire latent genome within all producer cell lines. qPCR assays were used to verify the expression of the remaining viral miRNAs in a subset of mutants. Induction of the lytic cycle leads to efficient production of progeny viruses that have been used to infect endothelial cells. Wt BAC16 and miR mutant iSLK producer cell lines are now available to the research community. PMID- 26907328 TI - Porcine Circovirus 2 Deploys PERK Pathway and GRP78 for Its Enhanced Replication in PK-15 Cells. AB - Porcine circovirus type 2 (PCV2) infection induces autophagy and apoptosis. These cellular responses could be connected with endoplasmic reticulum (ER) stress. It remains unknown if PCV2 induces ER stress and if autophagy or apoptosis is primary to PCV2 infection or secondary responses following ER stress. Here, we demonstrate that PCV2 triggered unfolded protein response (UPR) in PK-15 cells by activating the PERK/eIF2alpha pathway without concomitant activation of IRE1 or ATF6. Since ATF4 and CHOP were induced later than PERK/eIF2alpha, it is clear that persistent PCV2 infection could lead to selective activation of PERK via the PERK-eIF2alpha-ATF4-CHOP axis. Therefore, PERK activation could be part of the pro-apoptotic signaling via induced expression of CHOP by PCV2. Since PERK inhibition by GSK2606414 or RNA silencing or suppression of eIF2alpha dephosphorylation by salubrinal limited viral replication, we suppose that PCV2 deploys UPR to enhance its replication. Over-expression of GRP78 or treatment with tauroursodeoxycholic acid could enhance viral capsid expression and/or viral titers, indicating that these chaperones, endogenous or exogenous, could help correct folding of viral proteins. Our findings provide the first evidence that ER stress plays a role in the pathogenesis of PCV2 infection probably as part of autophagic and apoptotic responses. PMID- 26907329 TI - Identification and Comparison of Receptor Binding Characteristics of the Spike Protein of Two Porcine Epidemic Diarrhea Virus Strains. AB - Porcine epidemic diarrhea virus (PEDV), a member of Alphacoronavirus, has caused huge economic losses for the global pork industry recently. The spike (S) protein mediates PEDV entry into host cells. Herein, we investigated the interactions between the S protein and its receptor porcine aminopeptidase N (pAPN) or co receptor sugars. The C-terminal domain (CTD) of the S1 domain is bound to pAPN. The prototype strain demonstrated similar receptor-binding activity compared with the variant field isolate. Three loops at the tips of the beta-barrel domains did not play crucial roles in the PEDV S-pAPN association, indicating that PEDV conforms to a different receptor recognition model compared with transmissible gastroenteritis virus (TGEV), porcine respiratory CoV (PRCV), and human coronavirus NL63 (HCoV-NL63). The N-terminal domain (NTD) of the PEDV S1 domain could bind sugar, a possible co-receptor for PEDV. The prototype strain exhibited weaker sugar-binding activity compared with the variant field isolate. Strategies targeting the receptor binding domain (RBD) may be helpful for developing vaccines or antiviral drugs for PEDV. Understanding the differences in receptor binding between the prototype and the variant strains may provide insight into PEDV pathogenesis. PMID- 26907331 TI - Sweet Taste Receptor TAS1R2 Polymorphism (Val191Val) Is Associated with a Higher Carbohydrate Intake and Hypertriglyceridemia among the Population of West Mexico. AB - Some high-carbohydrate diets may lead to obesity and multiple metabolic disorders, including hypertriglyceridemia (HTG). This lipid abnormality is considered an important risk factor for cardiovascular disease and type 2 diabetes. The sweet taste receptor TAS1R2 polymorphism (Ile191Val) has been reported to be associated with carbohydrate intake. The aim of this study was to analyze the association of the TAS1R2 gene polymorphism with carbohydrate intake and HTG among the population of West Mexico. In a cross-sectional study, 441 unrelated subjects were analyzed for TAS1R2 genotypes (Ile/Ile, Ile/Val and Val/Val) by an allelic discrimination assay. Biochemical tests and a three-day food record were assessed. The Val/Val genotype carriers had a higher intake of total carbohydrates, fiber and servings of cereals and vegetables than the other genotype carriers. The Val/Val genotype conferred a higher risk for HTG than the Ile/Val and Ile/Ile genotypes (OR = 3.26, 95%CI 1.35-7.86, p = 0.006 and OR = 2.61, 95%CI 1.12-6.07, p = 0.02, respectively). Furthermore, the Val/Val genotype was associated with approximately 30% higher triglycerides compared with Ile/Val and Ile/Ile genotypes (beta = 44.09, 95%CI 9.94-78.25, p = 0.01 and beta = 45.7, 95%CI 10.85-80.54, p = 0.01, respectively). In conclusion, the Val/Val genotype of TAS1R2 was associated with a higher carbohydrate intake and HTG. PMID- 26907330 TI - Therapeutic Use of Native and Recombinant Enteroviruses. AB - Research on human enteroviruses has resulted in the identification of more than 100 enterovirus types, which use more than 10 protein receptors and/or attachment factors required in cell binding and initiation of the replication cycle. Many of these "viral" receptors are overexpressed in cancer cells. Receptor binding and the ability to replicate in specific target cells define the tropism and pathogenesis of enterovirus types, because cellular infection often results in cytolytic response, i.e., disruption of the cells. Viral tropism and cytolytic properties thus make native enteroviruses prime candidates for oncolytic virotherapy. Copy DNA cloning and modification of enterovirus genomes have resulted in the generation of enterovirus vectors with properties that are useful in therapy or in vaccine trials where foreign antigenic epitopes are expressed from or on the surface of the vector virus. The small genome size and compact particle structure, however, set limits to enterovirus genome modifications. This review focuses on the therapeutic use of native and recombinant enteroviruses and the methods that have been applied to modify enterovirus genomes for therapy. PMID- 26907332 TI - The Fto Gene Regulates the Proliferation and Differentiation of Pre-Adipocytes in Vitro. AB - The highly regulated differentiation and proliferation of pre-adipocytes play a key role in the initiation of obesity. Fat mass and obesity associated (FTO) is a novel gene strongly associated with the risk of obesity. A deficiency of FTO may cause growth retardation in addition to fat mass and adipocyte size reduction in vivo. To investigate the potential role of Fto gene on the proliferation and differentiation of pre-adipocytes, we generated Fto-knockdown and overexpressed 3T3-L1 cells. Using numerous proliferation assays our results suggest that Fto knockdown leads to suppression of proliferation, lower mitochondrial membrane potential, less cellular ATP, and decreased and smaller intracellular lipid droplets compared with controls (p < 0.05). Western blot analysis demonstrated that Fto knockdown can significantly suppress peroxisome proliferator-activated receptor gamma (PPARgamma) and glucose transporter type 4 (GLUT4) expression and inhibit Akt phosphorylation. By contrast, overexpression of Fto had the opposing effect on proliferation, mitochondrial membrane potential, ATP generation, in vitro differentiation, Akt phosphorylation, and PPARgamma and GLUT4 expression. Moreover, we demonstrated that Wortmannin, a phosphoinositide 3-kinase (PI3K) inhibitor, could inhibit phospho-Akt in Fto overexpressed 3T3-L1 cells. Taken together, the results suggest that Fto regulates the proliferation and differentiation of 3T3-L1 cells via multiple mechanisms, including PPARgamma and PI3K/Akt signaling. PMID- 26907333 TI - Feeding a Diet Enriched in Docosahexaenoic Acid to Lactating Dams Improves the Tolerance Response to Egg Protein in Suckled Pups. AB - The objective of this study was to determine the effect of feeding a maternal diet supplemented with docosahexaenoic acid (DHA) during the suckling period on the development of the immune system and oral tolerance (OT) in offspring. Dams were randomized to consume one of two nutritionally adequate diets throughout the suckling period: control (N = 12, 0% DHA) or DHA (N = 8, 0.9% DHA) diet. At 11 days, pups from each dam were randomly assigned to a mucosal OT challenge: the placebo or the ovalbumin (OVA) treatment. At three weeks, plasma immunoglobulins and splenocyte cytokine production ex vivo were measured. OVA-tolerized pups had a lower Th2 (IL-13) response to OVA despite the presence of more activated T cells and memory cells (CD27+, all p < 0.05). Feeding a high DHA diet improved the ability of splenocytes to respond to mitogens toward a skewed Th1 response and led to a higher IL-10 and a lower TGF-beta production after stimulation with OVA (all p < 0.05). Untolerized DHA-fed pups had lower plasma concentrations of OVA-specific immunoglobulin E (p for interaction < 0.05). Overall, feeding a high DHA maternal diet improves the tolerance response in untolerized suckled pups in a direction that is thought to be beneficial for the establishment of OT. PMID- 26907335 TI - Correction: Lozano-Baena, M.-D.; et al. Cancer Prevention and Health Benefices of Traditionally Consumed Borago officinalis Plants. Nutrients 2016, 8(1), 48. PMID- 26907334 TI - Cysteic Acid in Dietary Keratin is Metabolized to Glutathione and Liver Taurine in a Rat Model of Human Digestion. AB - Poultry feathers, consisting largely of keratin, are a low-value product of the poultry industry. The safety and digestibility of a dietary protein produced from keratin (KER) was compared to a cysteine-supplemented casein-based diet in a growing rat model for four weeks. KER proved to be an effective substitute for casein at 50% of the total dietary protein, with no changes in the rats' food intake, weight gain, organ weight, bone mineral density, white blood cell counts, liver glutathione, or blood glutathione. Inclusion of KER in the diet reduced total protein digestibility from 94% to 86% but significantly increased total dietary cysteine uptake and subsequent liver taurine levels. The KER diet also significantly increased caecum weight and significantly decreased fat digestibility, resulting in a lower proportion of body fat, and induced a significant increase in blood haemoglobin. KER is therefore a safe and suitable protein substitute for casein, and the cysteic acid in keratin is metabolised to maintain normal liver and blood glutathione levels. PMID- 26907336 TI - Sake Protein Supplementation Affects Exercise Performance and Biochemical Profiles in Power-Exercise-Trained Mice. AB - Exercise and fitness training programs have attracted the public's attention in recent years. Sports nutrition supplementation is an important issue in the global sports market. PURPOSE: In this study, we designed a power exercise training (PET) program with a mouse model based on a strength and conditional training protocol for humans. We tested the effect of supplementation with functional branched-chain amino acid (BCAA)-rich sake protein (SP) to determine whether the supplement had a synergistic effect during PET and enhanced athletic performance and resistance to fatigue. METHODS: Male ICR mice were divided into three groups (n = 8 per group) for four-week treatment: sedentary controls with vehicle (SC), and PET and PET groups with SP supplementation (3.8 g/kg, PET + SP). Exercise performance was evaluated by forelimb grip strength and exhaustive swimming time as well as changes in body composition and anti-fatigue activity levels of serum lactate, ammonia, glucose, and creatine kinase (CK) after a 15 min swimming exercise. The biochemical parameters were measured at the end of the experiment. RESULTS: four-week PET significantly increased grip strength and exhaustive swimming time and decreased epididymal fat pad (EFP) weight and area. Levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, and uric acid (UA) were significantly increased. PET + SP supplementation significantly decreased serum lactate, ammonia and CK levels after the 15-min swimming exercise. The resting serum levels of AST, ALT, CREA and UA were all significantly decreased with PET + SP. CONCLUSION: The PET program could increase the exercise performance and modulate the body composition of mice. PET with SP conferred better anti-fatigue activity, improved biochemical profiles, and may be an effective ergogenic aid in strength training. PMID- 26907337 TI - Protective Effect of Gallotannin-Enriched Extract Isolated from Galla Rhois against CCl4-Induced Hepatotoxicity in ICR Mice. AB - To investigate the toxicity, protective effects, and action mechanism of gallotannin-enriched extracts isolated from Galla Rhois (GEGR) against carbon tetrachloride (CCl4)-induced hepatotoxicity in Institute for Cancer Research (ICR) mice, alterations in serum biochemical indicators, histopathological structure, antioxidative status, hepatic apoptosis-related proteins, and liver fibrosis regulating factors were measured in mice pretreated with GEGR for five days before CCl4 injection. The GEGR/CCl4 treated group showed decreased levels of three serum marker enzymes (ALP, AST, and ALT) representing liver toxicity, although LDH levels remained constant. Necrotic area indicating hepatic cell death significantly inhibited, while malondialdehyde (MDA) concentration and superoxide dismutase (SOD) expression were dramatically recovered in the GEGR preadministrated group. In mechanism analyses of GEGR, the formation of active caspase-3 and enhancement of Bax/Bcl-2 expression was effectively inhibited in the GEGR/CCl4 treated group. The level of pro-inflammatory cytokines, TNF-alpha and IL-6, as well as the phosphorylation of p38 and JNK in the TNF-alpha downstream signaling pathway was rapidly recovered in the GEGR/CCl4 treated group, while anti-inflammatory cytokine (IL-10) increased slightly in the same group. Furthermore, the GEGR/CCl4 treated group showed a significant decrease in collagen accumulation results from alleviation of MMP-2 expression, TGF-beta1 secretion and the phosphorylation of Smad2/3. Taken together, these results suggest that GEGR may induce remarkable protective effects against hepatic injury induced by CCl4 treatment through upregulation of the anti-inflammatory and antioxidant system. PMID- 26907338 TI - Phytochemical Compounds and Antioxidant Capacity of Tucum-Do-Cerrado (Bactris setosa Mart), Brazil's Native Fruit. AB - This study identified major phenolic compounds of the tucum-do-cerrado (Bactris setosa) peel, as well as antioxidant activity and total phytochemical compound concentration of different extracts of the peel and pulp of this fruit. Phenolic compounds of the different extracts of tucum-do-cerrado peel were identified and quantified using a high-performance liquid chromatography system coupled to a diode array detector (DAD). Total phytochemical compound content was determined by spectrophotometric assays and the antioxidant activity by ferric reducing antioxidant power and beta-carotene/linoleic assays. Total phenolic, flavanols, total anthocyanins and yellow flavonoids concentration of tucum-do-cerrado were 122-, 14-, 264- and 61-fold higher in the peel than in the pulp, respectively. The aqueous, methanolic and ethanolic extracts of the tucum-do-cerrado peel exhibited higher antioxidant activity compared to its pulp. Flavanols, anthocyanins, flavones, phenolic acids and stilbenes were the main phenolic classes identified in the tucum-do-cerrado peel extracts. Results suggest that the antioxidant capacity and the phytochemical compound content of the tucum-do cerrado are mainly associated with the peel. Although flavonoids are the main compounds identified in tucum-do-cerrado peel, other phenolics identified in minor amounts, such as phenolic acids and stilbenes, may be responsible for the high antioxidant capacity of the fruit. PMID- 26907339 TI - Metabolic Effects of a 24-Week Energy-Restricted Intervention Combined with Low or High Dairy Intake in Overweight Women: An NMR-Based Metabolomics Investigation. AB - We investigated the effect of a 24-week energy-restricted intervention with low or high dairy intake (LD or HD) on the metabolic profiles of urine, blood and feces in overweight/obese women by NMR spectroscopy combined with ANOVA simultaneous component analysis (ASCA). A significant effect of dairy intake was found on the urine metabolome. HD intake increased urinary citrate, creatinine and urea excretion, and decreased urinary excretion of trimethylamine-N-oxide (TMAO) and hippurate relative to the LD intake, suggesting that HD intake was associated with alterations in protein catabolism, energy metabolism and gut microbial activity. In addition, a significant time effect on the blood metabolome was attributed to a decrease in blood lipid and lipoprotein levels due to the energy restriction. For the fecal metabolome, a trend for a diet effect was found and a series of metabolites, such as acetate, butyrate, propionate, malonate, cholesterol and glycerol tended to be affected. Overall, even though these effects were not accompanied by a higher weight loss, the present metabolomics data reveal that a high dairy intake is associated with endogenous metabolic effects and effects on gut microbial activity that potentially impact body weight regulation and health. Moreover, ASCA has a great potential for exploring the effect of intervention factors and identifying altered metabolites in a multi-factorial metabolomic study. PMID- 26907340 TI - A Comprehensive Analysis of Body Mass Index Effect on in Vitro Fertilization Outcomes. AB - The effect of a raised body mass index (BMI) on the outcome of assisted reproduction technology (ART) still represents a controversial issue. Even less clear is whether BMI acts with a potential detrimental effect on IVF outcomes via a deleterious effect on innate quality of oocytes or on the environmental milieu within the uterus. With the aim to better understand the mechanisms underlying the potential deleterious effect of an increased BMI on IVF outcomes, we have evaluated the effects of female BMI on number and quality of retrieved oocytes, fertilization rate, embryo score and incidences of ongoing pregnancy and live births among couples undergoing IVF in an Italian population. Data from 1602 women who underwent their first IVF cycle were retrospectively analyzed. A significantly reduced percentage of mature oocytes when comparing obese (BMI >= 30 kg/m2) and normal-weight patients (BMI = 18.50-24.99 kg/m2) was found. After adjusting for maternal age and other confounders, odds for ongoing pregnancy rate showed no differences across different BMI categories. However, a significant increased odds ratio (OR) could be observed for miscarriage rate in patients with BMI >= 25 (OR = 2.5; p = 0.04). These results should be taken into account in order to define optimal strategies for overweight and obese patients referring to ART procedures. PMID- 26907344 TI - Long-Term Blood Pressure Control Effect of Celiac Plexus Block with Botulinum Toxin. AB - Celiac plexus block (CPB) is one of the main treatment options for patients resistant to conventional antihypertensive drugs. We present a case of resistant hypertension (RHTN) that was treated with CPB using botulinum toxin. An 18-year old male patient with RHTN, who suffered from persistent hypertension even after combination therapy and a renal denervation procedure, was referred to our pain center for CPB. CPB using botulinum toxin following the use of only local anesthetics resulted in control of systolic blood pressure (BP) at ~150 mmHg for at least three months. PMID- 26907342 TI - Venoms of Heteropteran Insects: A Treasure Trove of Diverse Pharmacological Toolkits. AB - The piercing-sucking mouthparts of the true bugs (Insecta: Hemiptera: Heteroptera) have allowed diversification from a plant-feeding ancestor into a wide range of trophic strategies that include predation and blood-feeding. Crucial to the success of each of these strategies is the injection of venom. Here we review the current state of knowledge with regard to heteropteran venoms. Predaceous species produce venoms that induce rapid paralysis and liquefaction. These venoms are powerfully insecticidal, and may cause paralysis or death when injected into vertebrates. Disulfide-rich peptides, bioactive phospholipids, small molecules such as N,N-dimethylaniline and 1,2,5-trithiepane, and toxic enzymes such as phospholipase A2, have been reported in predatory venoms. However, the detailed composition and molecular targets of predatory venoms are largely unknown. In contrast, recent research into blood-feeding heteropterans has revealed the structure and function of many protein and non-protein components that facilitate acquisition of blood meals. Blood-feeding venoms lack paralytic or liquefying activity but instead are cocktails of pharmacological modulators that disable the host haemostatic systems simultaneously at multiple points. The multiple ways venom is used by heteropterans suggests that further study will reveal heteropteran venom components with a wide range of bioactivities that may be recruited for use as bioinsecticides, human therapeutics, and pharmacological tools. PMID- 26907343 TI - Heterologous Expression of Toxins from Bacterial Toxin-Antitoxin Systems in Eukaryotic Cells: Strategies and Applications. AB - Toxin-antitoxin (TA) systems are found in nearly all prokaryotic genomes and usually consist of a pair of co-transcribed genes, one of which encodes a stable toxin and the other, its cognate labile antitoxin. Certain environmental and physiological cues trigger the degradation of the antitoxin, causing activation of the toxin, leading either to the death or stasis of the host cell. TA systems have a variety of functions in the bacterial cell, including acting as mediators of programmed cell death, the induction of a dormant state known as persistence and the stable maintenance of plasmids and other mobile genetic elements. Some bacterial TA systems are functional when expressed in eukaryotic cells and this has led to several innovative applications, which are the subject of this review. Here, we look at how bacterial TA systems have been utilized for the genetic manipulation of yeasts and other eukaryotes, for the containment of genetically modified organisms, and for the engineering of high expression eukaryotic cell lines. We also examine how TA systems have been adopted as an important tool in developmental biology research for the ablation of specific cells and the potential for utility of TA systems in antiviral and anticancer gene therapies. PMID- 26907345 TI - Combined Effects of Lipophilic Phycotoxins (Okadaic Acid, Azapsiracid-1 and Yessotoxin) on Human Intestinal Cells Models. AB - Phycotoxins are monitored in seafood because they can cause food poisonings in humans. Phycotoxins do not only occur singly but also as mixtures in shellfish. The aim of this study was to evaluate the in vitro toxic interactions of binary combinations of three lipophilic phycotoxins commonly found in Europe (okadaic acid (OA), yessotoxin (YTX) and azaspiracid-1 (AZA-1)) using the neutral red uptake assay on two human intestinal cell models, Caco-2 and the human intestinal epithelial crypt-like cells (HIEC). Based on the cytotoxicity of individual toxins, we studied the interactions between toxins in binary mixtures using the combination index-isobologram equation, a method widely used in pharmacology to study drug interactions. This method quantitatively classifies interactions between toxins in mixtures as synergistic, additive or antagonistic. AZA-1/OA, and YTX/OA mixtures showed increasing antagonism with increasing toxin concentrations. In contrast, the AZA-1/YTX mixture showed increasing synergism with increasing concentrations, especially for mixtures with high YTX concentrations. These results highlight the hazard potency of AZA-1/YTX mixtures with regard to seafood intoxication. PMID- 26907346 TI - Venom of Parasitoid Pteromalus puparum Impairs Host Humoral Antimicrobial Activity by Decreasing Host Cecropin and Lysozyme Gene Expression. AB - Insect host/parasitoid interactions are co-evolved systems in which host defenses are balanced by parasitoid mechanisms to disable or hide from host immune effectors. Here, we report that Pteromalus puparum venom impairs the antimicrobial activity of its host Pieris rapae. Inhibition zone results showed that bead injection induced the antimicrobial activity of the host hemolymph but that venom inhibited it. The cDNAs encoding cecropin and lysozyme were screened. Relative quantitative PCR results indicated that all of the microorganisms and bead injections up-regulated the transcript levels of the two genes but that venom down-regulated them. At 8 h post bead challenge, there was a peak in the transcript level of the cecropin gene, whereas the peak of lysozyme gene occurred at 24 h. The transcripts levels of the two genes were higher in the granulocytes and fat body than in other tissues. RNA interference decreased the transcript levels of the two genes and the antimicrobial activity of the pupal hemolymph. Venom injections similarly silenced the expression of the two genes during the first 8 h post-treatment in time- and dose-dependent manners, after which the silence effects abated. Additionally, recombinant cecropin and lysozyme had no significant effect on the emergence rate of pupae that were parasitized by P. puparum females. These findings suggest one mechanism of impairing host antimicrobial activity by parasitoid venom. PMID- 26907347 TI - Bee Venom Phospholipase A2: Yesterday's Enemy Becomes Today's Friend. AB - Bee venom therapy has been used to treat immune-related diseases such as arthritis for a long time. Recently, it has revealed that group III secretory phospholipase A2 from bee venom (bee venom group III sPLA2) has in vitro and in vivo immunomodulatory effects. A growing number of reports have demonstrated the therapeutic effects of bee venom group III sPLA2. Notably, new experimental data have shown protective immune responses of bee venom group III sPLA2 against a wide range of diseases including asthma, Parkinson's disease, and drug-induced organ inflammation. It is critical to evaluate the beneficial and adverse effects of bee venom group III sPLA2 because this enzyme is known to be the major allergen of bee venom that can cause anaphylactic shock. For many decades, efforts have been made to avoid its adverse effects. At high concentrations, exposure to bee venom group III sPLA2 can result in damage to cellular membranes and necrotic cell death. In this review, we summarized the current knowledge about the therapeutic effects of bee venom group III sPLA2 on several immunological diseases and described the detailed mechanisms of bee venom group III sPLA2 in regulating various immune responses and physiopathological changes. PMID- 26907348 TI - Insight into the Mode of Action of Haedoxan A from Phryma leptostachya. AB - Haedoxan A (HA) is a major active ingredient in the herbaceous perennial plant lopseed (Phryma leptostachya L.), which is used as a natural insecticide against insect pests in East Asia. Here, we report that HA delayed the decay rate of evoked excitatory junctional potentials (EJPs) and increased the frequency of miniature EJPs (mEJPs) on the Drosophila neuromuscular junction. HA also caused a significant hyperpolarizing shift of the voltage dependence of fast inactivation of insect sodium channels expressed in Xenopus oocytes. Our results suggest that HA acts on both axonal conduction and synaptic transmission, which can serve as a basis for elucidating the mode of action of HA for further designing and developing new effective insecticides. PMID- 26907349 TI - The Role of HPV in Head and Neck Cancer Stem Cell Formation and Tumorigenesis. AB - The cancer stem cell (CSC) theory proposes that a minority of tumor cells are capable of self-replication and tumorigenesis. It is these minority of cells that are responsible for cancer metastasis and recurrence in head and neck squamous cell cancers (HNSCC). Human papilloma virus (HPV)-related cancer of the oropharynx is becoming more prevalent, which makes understanding of the relationship between HPV and CSCs more important than ever. This relationship is critical because CSC behavior can be predicted based on cell surface markers, which makes them a suitable candidate for targeted therapy. New therapies are an exciting opportunity to advance past the stalled outcomes in HNSCC that have plagued patients and clinicians for several decades. PMID- 26907350 TI - Cimetidine and Clobenpropit Attenuate Inflammation-Associated Colorectal Carcinogenesis in Male ICR Mice. AB - Histamine and histamine receptors (Hrhs) have been identified as critical molecules during inflammation and carcinogenesis. This study was conducted to determine the effects of Hrh1-Hrh3 antagonists on inflammation-associated colorectal carcinogenesis. Male ICR mice were treated with azoxymethane (AOM, 10 mg/kg bw, i.p.) and 1.5% dextran sodium sulfate (DSS, drinking water for 7 days) to induce colorectal carcinogenesis. The mice were then fed diets containing test chemical (500 ppm terfenadine, 500 ppm cimetidine or 10 ppm clobenpropit) for 15 weeks. At week 18, feeding with the diets containing cimetidine (Hrh2 antagonist) and clobenpropit (Hrh3 antagonist/inverse agonist) significantly lowered the multiplicity of colonic adenocarcinoma. Terfenadine (Hrh1 antagonist) did not affect AOM-DSS-induced colorectal carcinogenesis. Adenocarcinoma cells immunohistochemically expressed Hrh1, Hrh2, Hrh3 and Hrh4 with varied intensities. Because clobenpropit is also known to be a Hrh4 receptor agonist, Hrh2, Hrh3 and Hrh4 may be involved in inflammation-related colorectal carcinogenesis. Additional data, including the mRNA expression of pro inflammatory cytokines and inducible inflammatory enzymes in the colonic mucosa, are also presented. PMID- 26907351 TI - Cluster Analysis of Physical and Cognitive Ageing Patterns in Older People from Shanghai. AB - This study investigated the relationship between education, cognitive and physical function in older age, and their respective impacts on activities of daily living (ADL). Data on 148 older participants from a community-based sample recruited in Shanghai, China, included the following measures: age, education, ADL, grip strength, balance, gait speed, global cognition and verbal memory. The majority of participants in the present cohort were cognitively and physically healthy and reported no problems with ADL. Twenty-eight percent of participants needed help with ADL, with the majority of this group being over 80 years of age. Significant predictors of reductions in functional independence included age, balance, global cognitive function (MMSE) and the gait measures. Cluster analysis revealed a protective effect of education on cognitive function that did not appear to extend to physical function. Consistency of such phenotypes of ageing clusters in other cohort studies may provide helpful models for dementia and frailty prevention measures. PMID- 26907352 TI - Why Serological Responses during Cystitis are Limited. AB - The high frequency of urinary tract infections (UTIs), some of which appear to be endogenous relapses rather than reinfections by new isolates, point to defects in the host's memory immune response. It has been known for many decades that, whereas kidney infections evoked an antibody response to the infecting bacteria, infections limited to the bladder failed to do so. We have identified the existence of a broadly immunosuppressive transcriptional program associated with the bladder, but not the kidneys, during infection of the urinary tract that is dependent on bladder mast cells. This involves the localized secretion of IL-10 and results in the suppression of humoral immune responses in the bladder. Mast cell-mediated immune suppression could suggest a role for these cells in critically balancing the needs to clear infections with the imperative to prevent harmful immune reactions in the host. PMID- 26907353 TI - Histone Deacetylase 6 Regulates Bladder Architecture and Host Susceptibility to Uropathogenic Escherichia coli. AB - Histone deacetylase 6 (HDAC6) is a non-canonical, mostly cytosolic histone deacetylase that has a variety of interacting partners and substrates. Previous work using cell-culture based assays coupled with pharmacological inhibitors and gene-silencing approaches indicated that HDAC6 promotes the actin- and microtubule-dependent invasion of host cells by uropathogenic Escherichia coli (UPEC). These facultative intracellular pathogens are the major cause of urinary tract infections. Here, we examined the involvement of HDAC6 in bladder colonization by UPEC using HDAC6 knockout mice. Though UPEC was unable to invade HDAC6(-/-) cells in culture, the bacteria had an enhanced ability to colonize the bladders of mice that lacked HDAC6. This effect was transient, and by six hours post-inoculation bacterial titers in the HDAC6(-/-) mice were reduced to levels seen in wild type control animals. Subsequent analyses revealed that the mutant mice had greater bladder volume capacity and fluid retention, along with much higher levels of acetylated a-tubulin. In addition, infiltrating neutrophils recovered from the HDAC6(-/-) bladder harbored significantly more viable bacteria than their wild type counterparts. Cumulatively, these changes may negate any inhibitory effects that the lack of HDAC6 has on UPEC entry into individual host cells, and suggest roles for HDAC6 in other urological disorders such as urinary retention. PMID- 26907354 TI - The Contribution of Equitation Science to Minimising Horse-Related Risks to Humans. AB - Equitation science is an evidence-based approach to horse training and riding that focuses on a thorough understanding of both equine ethology and learning theory. This combination leads to more effective horse training, but also plays a role in keeping horse riders and trainers safe around horses. Equitation science underpins ethical equitation, and recognises the limits of the horse's cognitive and physical abilities. Equitation is an ancient practice that has benefited from a rich tradition that sees it flourishing in contemporary sporting pursuits. Despite its history, horse-riding is an activity for which neither horses nor humans evolved, and it brings with it significant risks to the safety of both species. This review outlines the reasons horses may behave in ways that endanger humans and how training choices can exacerbate this. It then discusses the recently introduced 10 Principles of Equitation Science and explains how following these principles can minimise horse-related risk to humans and enhance horse welfare. PMID- 26907356 TI - Streptococcus pneumoniae Serotype Distribution and Pneumococcal Conjugate Vaccine Serotype Coverage among Pediatric Patients in East and Southeast Asia, 2000-2014: a Pooled Data Analysis. AB - Pneumococcal infection is one of the leading causes of death worldwide, especially in children of developing and underdeveloped countries. Capsular polysaccharide-based vaccines are available for the prevention of this disease. A 7-valent pneumococcal conjugate vaccine (PCV7) was licensed in 2000 for use in children less than two years of age. Subsequently, to broaden the protection, 10 valent (PCV10) and 13-valent (PCV13) vaccines were licensed in 2009 and 2010, respectively. All of these conjugate vaccines elicit an immune response that only provides protection against the infection of S. pneumoniae serotypes included in the formulation. Profiles of S. pneumoniae serotype distribution and serotype coverage for both PCV7 and PCV13 have been reported in some Asian countries/territories. But the published results cannot provide conclusive information due to the difference in studied population and geographic areas. The goals of this review are to obtain an accurate estimate of serotype coverage for PCV7, PCV10, and PCV13 and examine the change in the S. pneumoniae serotype distribution after PCV7 use among pediatric patients in East and Southeast Asia through the analysis of pooled data that were published in the English literature between 2000 and 2014. PMID- 26907355 TI - Mitochondrial Dysfunction in Cancer and Neurodegenerative Diseases: Spotlight on Fatty Acid Oxidation and Lipoperoxidation Products. AB - In several human diseases, such as cancer and neurodegenerative diseases, the levels of reactive oxygen species (ROS), produced mainly by mitochondrial oxidative phosphorylation, is increased. In cancer cells, the increase of ROS production has been associated with mtDNA mutations that, in turn, seem to be functional in the alterations of the bioenergetics and the biosynthetic state of cancer cells. Moreover, ROS overproduction can enhance the peroxidation of fatty acids in mitochondrial membranes. In particular, the peroxidation of mitochondrial phospholipid cardiolipin leads to the formation of reactive aldehydes, such as 4-hydroxynonenal (HNE) and malondialdehyde (MDA), which are able to react with proteins and DNA. Covalent modifications of mitochondrial proteins by the products of lipid peroxidation (LPO) in the course of oxidative cell stress are involved in the mitochondrial dysfunctions observed in cancer and neurodegenerative diseases. Such modifications appear to affect negatively mitochondrial integrity and function, in particular energy metabolism, adenosine triphosphate (ATP) production, antioxidant defenses and stress responses. In neurodegenerative diseases, indirect confirmation for the pathogenetic relevance of LPO-dependent modifications of mitochondrial proteins comes from the disease phenotypes associated with their genetic alterations. PMID- 26907357 TI - Epicardial Epithelial-to-Mesenchymal Transition in Heart Development and Disease. AB - The epicardium is an epithelial monolayer that plays a central role in heart development and the myocardial response to injury. Recent developments in our understanding of epicardial cell biology have revealed this layer to be a dynamic participant in fundamental processes underlying the development of the embryonic ventricles, the coronary vasculature, and the cardiac valves. Likewise, recent data have identified the epicardium as an important contributor to reparative and regenerative processes in the injured myocardium. These essential functions of the epicardium rely on both non-cell autonomous and cell-autonomous mechanisms, with the latter featuring the process of epicardial Epithelial-to-Mesenchymal Transition (EMT). This review will focus on the induction and regulation of epicardial EMT, as it pertains to both cardiogenesis and the response of the myocardium to injury. PMID- 26907359 TI - Direct Bandgap Light Emission from Strained Germanium Nanowires Coupled with High Q Nanophotonic Cavities. AB - A silicon-compatible light source is the final missing piece for completing high speed, low-power on-chip optical interconnects. In this paper, we present a germanium nanowire light emitter that encompasses all the aspects of potential low-threshold lasers: highly strained germanium gain medium, strain-induced pseudoheterostructure, and high-Q nanophotonic cavity. Our nanowire structure presents greatly enhanced photoluminescence into cavity modes with measured quality factors of up to 2000. By varying the dimensions of the germanium nanowire, we tune the emission wavelength over more than 400 nm with a single lithography step. We find reduced optical loss in optical cavities formed with germanium under high (>2.3%) tensile strain. Our compact, high-strain cavities open up new possibilities for low-threshold germanium-based lasers for on-chip optical interconnects. PMID- 26907358 TI - Transcriptional profiling of human smooth muscle cells infected with gingipain and fimbriae mutants of Porphyromonas gingivalis. AB - Porphyromonas gingivalis (P. gingivalis) is considered to be involved in the development of atherosclerosis. However, the role of different virulence factors produced by P. gingivalis in this process is still uncertain. The aim of this study was to investigate the transcriptional profiling of human aortic smooth muscle cells (AoSMCs) infected with wild type, gingipain mutants or fimbriae mutants of P. gingivalis. AoSMCs were exposed to wild type (W50 and 381), gingipain mutants (E8 and K1A), or fimbriae mutants (DPG-3 and KRX-178) of P. gingivalis. We observed that wild type P. gingivalis changes the expression of a considerable larger number of genes in AoSMCs compare to gingipain and fimbriae mutants, respectively. The results from pathway analysis revealed that the common differentially expressed genes for AoSMCs infected by 3 different wild type P. gingivalis strains were enriched in pathways of cancer, cytokine-cytokine receptor interaction, regulation of the actin cytoskeleton, focal adhesion, and MAPK signaling pathway. Disease ontology analysis showed that various strains of P. gingivalis were associated with different disease profilings. Our results suggest that gingipains and fimbriae, especially arginine-specific gingipain, produced by P. gingivalis play important roles in the association between periodontitis and other inflammatory diseases, including atherosclerosis. PMID- 26907360 TI - Thinking big by thinking small: advances in mechanobiology across the length scales. AB - The field of mechanobiology provides an integrative understanding of biology and engineering principles. Mechanical forces are now well-established to provide a physical stimulus to help maintain normal tissue function, yet little is understood as to how forces experienced at various length scales influence cell behaviour and tissue function. In this Research Highlight, we describe recent technical innovations that have enabled advanced insight into the cellular microenvironment across a range of length scales. PMID- 26907361 TI - Modulation of selenium tissue distribution and selenoprotein expression in Atlantic salmon (Salmo salar L.) fed diets with graded levels of plant ingredients. AB - Increased substitution of marine ingredients by terrestrial plant products in aquafeeds has been proven to be suitable for Atlantic salmon farming. However, a reduction in n-3 long-chain PUFA is a consequence of this substitution. In contrast, relatively little attention has been paid to the effects of fishmeal and oil substitution on levels of micronutrients such as Se, considering fish are major sources of this mineral for human consumers. To evaluate the effects of dietary marine ingredient substitution on tissue Se distribution and the expression of Se metabolism and antioxidant enzyme genes, Atlantic salmons were fed three feeds based on commercial formulations with increasing levels of plant proteins (PP) and vegetable oil. Lipid content in flesh did not vary at any sampling point, but it was higher in the liver of 1 kg of fish fed higher PP. Fatty acid content reflected dietary input and was related to oxidation levels (thiobarbituric acid-reactive substances). Liver had the highest Se levels, followed by head kidney, whereas the lowest contents were found in brain and gill. The Se concentration of flesh decreased considerably with high levels of substitution, reducing the added value of fish consumption. Only the brain showed significant differences in glutathione peroxidase, transfer RNA selenocysteine 1 associated protein 1b and superoxide dismutase expression, whereas no significant regulation of Se-related genes was found in liver. Although Se levels in the diets satisfied the essential requirements of salmon, high PP levels led to a reduction in the supply of this essential micronutrient. PMID- 26907362 TI - Do orthopaedic trauma patients develop higher rates of cardiac complications? An analysis of 56,000 patients. AB - PURPOSE: Less than 5 % of orthopaedic patients develop postoperative cardiac complications; however, there are little data suggesting which orthopaedic patients are at greatest risk. In an era where emerging reimbursement models place an emphasis on quality, reducing complications through perioperative planning will be of paramount importance for orthopaedic surgeons. The purpose of this study was to determine whether orthopaedic trauma patients are at greater risk for postoperative cardiac complications and to reveal which factors are most predictive of these complications. METHODS: All orthopaedic patients were identified in the 2006-2013 ACS-NSQIP database. Cardiac complications were defined as cardiac arrests or myocardial infarctions within 30 days following surgery. Chi squared analysis determined differences in cardiac complication rates between trauma and non-trauma patients. Bivariate analysis incorporating over 40 patient/surgical characteristics determined significant associations between patient characteristics and cardiac complications. These factors were incorporated into a multivariate regression model to identify predictive risk factors for cardiac complications. RESULTS: The presence of a traumatic injury resulted in greater odds of developing cardiac complications (OR: 1.645, p < 0.001). The cardiac complication rate in the trauma group was 1.3 % compared to 0.3 % in the non-trauma group (p < 0.001). For trauma patients, ventilator use (OR: 27.354, p = 0.004), recent transfusion (OR: 19.780, p = 0.001), and history of coma (OR: 17.922, p = 0.020) were most predictive of cardiac complications. CONCLUSION: Orthopaedic trauma patients are more likely to develop cardiac complications than non-trauma patients. To reduce cardiac complications, orthopaedic traumatologists should be aware of patient risk factors including ventilator use, blood transfusion, and history of coma. PMID- 26907363 TI - Recurrence of a pT2N0cM0 Lower Third Gastric Cancer with No. 6 Lymph Node Micrometastasis after R0 Extended Surgery. Should Adjuvant Therapy be Performed in Conventionally Node-Negative but Micrometastasis-Positive pT2 Gastric Cancer? PMID- 26907364 TI - FDG-PET/ceCT is useful to predict recurrence of Pseudomyxoma peritonei. AB - PURPOSE: Pseudomyxoma peritonei (PMP) is a rare peritoneal neoplasm originating from appendicular tumours. There is no consolidated data available in the literature about the precise role of [(18)F] fluorodesoxy-D-glucose Positron Emission Tomography / contrast enhanced Computed Tomography (FDG-PET/ceCT). The aim of this study was to evaluate the correlation between preoperative FDG PET/ceCT (qualitative and semi-quantitative assessment) and progression free survival (PFS) of patients treated for PMP. METHODS: All patients scheduled for PMP treatment by cytoreductive unicentric surgery, intraperitoneal chemotherapy (HIPEC), and who underwent a FDG-PET/ceCT between February 2008 and January 2014, were included. No previous treatment was performed (except biopsy or appendectomy). FDG-PET/ceCT was interpreted by two nuclear physicians in consensus. Positive FDG-PET/ceCT scans were further labelled in diffuse disease and poly/mono focal disease. SUVmax was measured based on post-operative reports. The Peritoneal Cancer Index (PCI) and Completeness of CytoReduction Score (CCR) were assessed after surgery. RESULTS: Fifty-six patients were included in this study, with a mean age of 56-years-old and a mean follow-up of 29.3 months. SUVmax, with a cut-off at 2.02, was predictive for the PFS on multivariate analysis. No differences were observed between diffuse disease and focal disease on PFS for progression free survival, PCI, and SUVmax (p = 0.1). Post-operative CCR was not significantly correlated with SUVmax or FDG-PET/ceCT qualitative assessment. CONCLUSION: SUVmax on preoperative FDG-PET/ceCT was an independent predictive factor for PFS in PMP. Further studies are needed to explore if FDG PET/ceCT could potentially predict post-operative CCR. PMID- 26907365 TI - Externalizing behaviors of Ukrainian children: The role of parenting. AB - The purpose of this study was to assess the association of positive and negative parenting with child externalizing problems. Quantitative data were collected during face-to-face interviews with 320 parents of children 9-16 years of age (50% males) in 11 communities in Eastern, Southern, and Central Ukraine. The study estimated the relationship between parenting practices and child externalizing behaviors such as aggression, delinquency, and attention problems. Results revealed that positive parenting, child monitoring, and avoidance of corporal punishment were associated with fewer child externalizing symptoms. Results also indicated that child male gender and single parenting had significant and positive association with child externalizing behaviors. This study extends international psychosocial knowledge on children and families. These findings can be used to design programs and foster dialogs about the role of family and social environments in the development of externalizing disorder among researchers, representatives of governmental and nongovernmental organizations, and mass media that work with child abuse prevention in Ukraine. PMID- 26907366 TI - Quantum state transfer and controlled-phase gate on one-dimensional superconducting resonators assisted by a quantum bus. AB - We propose a quantum processor for the scalable quantum computation on microwave photons in distant one-dimensional superconducting resonators. It is composed of a common resonator R acting as a quantum bus and some distant resonators rj coupled to the bus in different positions assisted by superconducting quantum interferometer devices (SQUID), different from previous processors. R is coupled to one transmon qutrit, and the coupling strengths between rj and R can be fully tuned by the external flux through the SQUID. To show the processor can be used to achieve universal quantum computation effectively, we present a scheme to complete the high-fidelity quantum state transfer between two distant microwave photon resonators and another one for the high-fidelity controlled-phase gate on them. By using the technique for catching and releasing the microwave photons from resonators, our processor may play an important role in quantum communication as well. PMID- 26907368 TI - A Primary Screening and Applying of Plant Volatiles as Repellents to Control Whitefly Bemisia tabaci (Gennadius) on Tomato. AB - With the goal of finding a new way to reduce population densities of Bemisia tabaci biotype Q in greenhouses, seven repellent volatile chemicals and their combinations were screened. The mixture of DLCO (D-limonene, citral and olive oil (63:7:30)) had a better cost performance(SC50 = 22.59 mg/ml)to repel whiteflies from settling than the other mixtures or single chemicals. In the greenhouse, in both the choice test and the no-choice tests, the number of adult whiteflies that settled on 1% DLCO-treated tomato plants was significantly lower than those settling on the control plants for the different exposure periods (P < 0.01). In the choice test, the egg amount on the treated tomato plants was significantly lower (P < 0.01) than that on the control plants, but there was no significant difference (P > 0.05) between the number of eggs on treated and control plants in the no-choice test. Compared with the controls, 1% DLCO did not cause significantly statistic mortality rates (P > 0.05) out of different living stages of B. tabaci. The tests for evaluating the repellent efficacy, showed that a slow releasing bottle containing the mixture had a period of efficacy of 29 days, and the application of this mixture plus a yellow board used as a push-pull strategy in the greenhouse was also effective. PMID- 26907369 TI - Different pollinator assemblages ensure reproductive success of Cleisostoma linearilobatum (Orchidaceae) in fragmented holy hill forest and traditional tea garden. AB - Orchids are generally recognized to have specialist pollination systems and low fruit set is often thought to be characteristic of the family. In this study, we investigated the reproductive ecology of Cleisostoma linearilobatum, an epiphytic tropical orchid, in a holy hill forest fragment and a traditional tea garden in SW China using comparable methods. C. linearilobatum is self-compatible and dependent on insects for pollination. Fruit production in natural conditions was both pollinator- and resource-limited. However, the natural fruit set remained stable over multiple years at both sites. Pollination observations showed that C. linearilobatum has a generalized pollination system and seven insect species were observed as legitimate pollinators. Although the visit frequencies of different pollinators were different in the two sites, the pollinator assemblages ensured reproductive success of C. linearilobatum in both study sites over multiple years. The results partly explain why C. linearilobatum is so successful in the area, and also suggest that holy hill forest fragments and traditional tea gardens in Xishuangbanna are important in preserving orchids, especially those with generalist pollination. PMID- 26907370 TI - Examining the Role of Perioperative Nerve Blocks in Hip Arthroscopy: A Systematic Review. AB - PURPOSE: This systematic review examined the efficacy of perioperative nerve blocks for pain control after hip arthroscopy. METHODS: The databases Embase, PubMed, and Medline were searched on June 2, 2015, for English-language studies that reported on the use of perioperative nerve blocks for hip arthroscopy. The studies were systematically screened and data abstracted in duplicate. RESULTS: Nine eligible studies were included in this review (2 case reports, 2 case series, 3 non-randomized comparative studies, and 2 randomized controlled trials). In total, 534 patients (534 hips), with a mean age of 37.2 years, who underwent hip arthroscopy procedures were administered nerve blocks for pain management. Specifically, femoral (2 studies), fascia iliaca (2 studies), lumbar plexus (3 studies), and L1 and L2 paravertebral (2 studies) nerve blocks were used. All studies reported acceptable pain scores after the use of nerve blocks, and 4 studies showed significantly lower postoperative pain scores acutely with the use of nerve blocks over general anesthesia alone. The use of nerve blocks also resulted in a decrease in opioid consumption in 4 studies and provided a higher level of patient satisfaction in 2 studies. No serious acute complications were reported in any study, and long-term complications from lumbar plexus blocks, such as local anesthetic system toxicity (0.9%) and long-term neuropathy (2.8%), were low in incidence. CONCLUSIONS: The use of perioperative nerve blocks provides effective pain management after hip arthroscopy and may be more effective in decreasing acute postoperative pain and supplemental opioid consumption than other analgesic techniques. LEVEL OF EVIDENCE: Level IV, systematic review of Level I to Level IV studies. PMID- 26907371 TI - SLAP Lesions: Trends in Treatment. AB - PURPOSE: To determine the trends in SLAP repairs over time, including patient age, and percentage of SLAP repairs versus other common shoulder arthroscopic procedures. METHODS: The records of 4 sports or shoulder/elbow fellowship trained orthopaedic surgeons were used to identify the total number of common shoulder arthroscopic cases performed between 2004 and 2014 using current procedural terminology codes (CPT): 29822, 29823, 29826, 29827, 29806, 29807, 29825, and 29828. The number of SLAP repairs (CPT code 29807) as a combined or isolated procedure were recorded, and the classification of SLAP type was undertaken using operative reports. Patient age was recorded. Linear regression was used to determine statistical significance. RESULTS: There were 9,765 patients who underwent arthroscopic shoulder procedures using the defined CPT codes between 2004 and 2014 by our 4 orthopaedic surgeons. Of these, 619 underwent a SLAP repair (6.3%); average age 31.2 +/- 11.9. The age of patients undergoing SLAP repair significantly decreased over time (P < .001, R(2) = 0.794). Most SLAP repairs were performed on type II SLAP tears (P = .015, R(2) = 0.503). The percentage of SLAP repairs compared with the total number of shoulder arthroscopic surgeries and total number of patients who underwent SLAP repair significantly decreased over time (P < .001, R(2) = 0.832 and P = .002, R(2) = 0.674, respectively). Conversely, the number and percentage of biceps tenodeses are increasing over time (P = .0024 and P = .0099, respectively). CONCLUSIONS: Over the past 10 years, the total number of biceps tenodeses has increased, whereas the number and relative percentage of SLAP repairs within our practice have decreased. The average age of patients undergoing SLAP repair is decreasing, and most SLAP repairs are performed for type II SLAP tears. LEVEL OF EVIDENCE: Level IV, therapeutic case series. PMID- 26907372 TI - Burden of Infected Diabetic Foot Ulcers on Hospital Admissions and Costs. AB - BACKGROUND: Costs related to diabetic foot ulcer (DFU) care are greater than $1 billion annually and rising. We sought to describe the impact of diabetes mellitus (DM) on foot ulcer admissions in the United States, and to investigate potential explanations for rising hospital costs. METHODS: The Nationwide Inpatient Sample (2005-2010) was queried using International Classification of Diseases, 9th Revision (ICD-9) codes for a primary diagnosis of foot ulceration. Multivariable analyses were used to compare outcomes and per-admission costs among patients with foot ulceration and DM versus non-DM. RESULTS: In total, 962,496 foot ulcer patients were admitted over the study period. The overall rate of admissions was relatively stable over time, but the ratio of DM versus non-DM admissions increased significantly (2005: 10.2 vs. 2010: 12.7; P < 0.001). Neuropathy and infection accounted for 90% of DFU admissions, while peripheral vascular disease accounted for most non-DM admissions. Admissions related to infection rose significantly among DM patients (2005: 39,682 vs. 2010: 51,660; P < 0.001), but remained stable among non-DM patients. Overall, DM accounted for 83% and 96% of all major and minor amputations related to foot ulcers, respectively, and significantly increased cost of care (DM: $1.38 vs. non-DM: $0.13 billion/year; P < 0.001). Hospital costs per DFU admission were significantly higher for patients with infection compared with all other causes ($11,290 vs. $8,145; P < 0.001). CONCLUSIONS: Diabetes increases the incidence of foot ulcer admissions by 11-fold, accounting for more than 80% of all amputations and increasing hospital costs more than 10-fold over the 5 years. The majority of these costs are related to the treatment of infected foot ulcers. Education initiatives and early prevention strategies through outpatient multidisciplinary care targeted at high-risk populations are essential to preventing further increases in what is already a substantial economic burden. PMID- 26907373 TI - Endovascular Treatment of a Ruptured Innominate Artery Aneurysm in Behcet Disease. AB - In Behcet disease (BD), vascular complication such as false aneurysm formation is common after surgical treatment in the arterial lesion, and the optimal treatment method remains controversial. Concerning the innominate artery aneurysm, lack of experience due to its rarity in vasculo BD makes decision making even more difficult. We report a ruptured innominate artery aneurysm in a 70-year-old man with BD, which was successfully treated by innominate artery stent grafting through the right common carotid artery, axillo-axillary artery bypass grafting, and right subclavian artery coil embolization. The patient is doing well without any vascular complications at eighth postoperative month. PMID- 26907374 TI - [Kikuchi-Fujimoto's disease or histiocytic necrotizing lymphadenitis: A report of two familial cases]. AB - INTRODUCTION: The histiocytic necrotizing lymphadenitis or Kikuchi-Fujimoto's disease is characterized by a lymph node inflammation whose similarity with systemic lupus is generally admitted. CASE REPORT: Our description of two familial cases aims at raising the hypothesis of the existence of a genetic background in this disease following the example of what is observed in the autoimmune diseases. CONCLUSION: Pathophysiology of Kikuchi-Fujimoto's disease is probably multifactorial and may include predisposing genetic background and a possible infectious triggering event. PMID- 26907375 TI - Sex specific adaptations in placental biometry of overweight and obese women. AB - INTRODUCTION: Placental biometry at birth has been shown to predict chronic disease in later life. We hypothesized that maternal overweight/obesity, a state of low-grade inflammation and risk factor for adverse pregnancy outcome, could negatively influence placental development and that differences would be sex specific. METHODS: 696 women (537 normal-weight, NW; 112 overweight, OW; 47 obese, OB) with singleton uncomplicated pregnancies were prospectively enrolled at term delivery. Gestational age, maternal (age, height, pre-pregnancy BMI, gestational weight gain -GWG, hemoglobin, hematocrit and glycemia), fetal (weight, length, ponderal index, cranial circumference) and placental (weight, diameters) data were collected. Placental area, thickness and efficiency (fetal/placental weight ratio, F/P) were calculated. RESULTS: GWG was within standard recommendations in OB, while OW exceeded it. Placental weight was significantly higher in OW versus NW, but not in OB, leading to significantly higher placental thickness and lower F/P in this group. In the total population, a significant interaction effect between maternal BMI and fetal sex on placental weight and efficiency was found. Indeed, differences in placental parameters were present only in female offspring. DISCUSSION: In our population of OW and OB uncomplicated pregnancies only OW women, presenting GWG over standard recommendations, had thicker and less efficient placentas. We also reported different placental adaptation depending on fetal sex, with significant changes only in female fetuses. This may be part of a female-specific strategy aiming to ensure survival if another adverse event occurs. Customized counseling according to maternal BMI and fetal sex should be evaluated in clinical care. PMID- 26907376 TI - The ABCG2 efflux transporter from rabbit placenta: Cloning and functional characterization. AB - In human placenta, the ATP-binding cassette efflux transporter ABCG2 is highly expressed in syncytiotrophoblast cells and mediates cellular excretion of various drugs and toxins. Hence, physiological ABCG2 activity substantially contributes to the fetoprotective placenta barrier function during gestation. Developmental toxicity studies are often performed in rabbit. However, despite its toxicological relevance, there is no data so far on functional ABCG2 expression in this species. Therefore, we cloned ABCG2 from placenta tissues of chinchilla rabbit. Sequencing showed 84-86% amino acid sequence identity to the orthologues from man, rat and mouse. We transduced the rabbit ABCG2 clone (rbABCG2) in MDCKII cells and stable rbABCG2 gene and protein expression was shown by RT-PCR and Western blot analysis. The rbABCG2 efflux activity was demonstrated with the Hoechst H33342 assay using the specific ABCG2 inhibitor Ko143. We further tested the effect of established human ABCG2 (hABCG2) drug substrates including the antibiotic danofloxacin or the histamine H2-receptor antagonist cimetidine on H33342 accumulation in MDCKII-rbABCG2 or -hABCG2 cells. Human therapeutic plasma concentrations of all tested drugs caused a comparable competitive inhibition of H33342 excretion in both ABCG2 clones. Altogether, we first showed functional expression of the ABCG2 efflux transporter in rabbit placenta. Moreover, our data suggest a similar drug substrate spectrum of the rabbit and the human ABCG2 efflux transporter. PMID- 26907377 TI - Abnormal labyrinthine zone in the Hectd1-null placenta. AB - INTRODUCTION: The labyrinthine zone of the placenta is where exchange of nutrients and waste occurs between maternal and fetal circulations. Proper development of the placental labyrinth is essential for successful growth of the developing fetus and abnormalities in placental development are associated with intrauterine growth restriction (IUGR), preeclampsia and fetal demise. Our previous studies demonstrate that Hectd1 is essential for development of the junctional and labyrinthine zones of the placenta. Here we further characterize labyrinthine zone defects in the Hectd1 mutant placenta. METHODS: The structure of the mutant placenta was compared to wildtype littermates using histological methods. The expression of cell type specific markers was examined by immunohistochemistry and in situ hybridization. RESULTS: Hectd1 is expressed in the labyrinthine zone throughout development and the protein is enriched in syncytiotrophoblast layer type I cells (SynT-I) and Sinusoidal Trophoblast Giant cells (S-TGCs) in the mature placenta. Mutation of Hectd1 results in pale placentas with frequent hemorrhages along with gross abnormalities in the structure of the labyrinthine zone including a smaller overall volume and a poorly elaborated fetal vasculature that contain fewer fetal blood cells. Examination of molecular markers of labyrinthine trophoblast cell types reveals increased Dlx3 positive cells and Syna positive SynT-I cells, along with decreased Hand1 and Ctsq positive sinusoidal trophoblast giant cells (S-TGCs). DISCUSSION: Together these defects indicate that Hectd1 is required for development of the labyrinthine zonethe mouse placenta. PMID- 26907378 TI - Relationship between folate transporters expression in human placentas at term and birth weights. AB - BACKGROUND: Adequate folate levels are essential for successful pregnancy outcomes. We aimed to study the relationship between placental mRNA and protein levels of folate transporters to birth weight. METHODS: Placental folate transporters (FOLR1, RFC1 and HCP1/PCFT) mRNA and protein levels in basal (BP) and chorionic plate (CP) of small (SGA), appropriate (AGA) and large (LGA) for gestational age term infants (>=37 weeks gestation, n = 111) were determined by real-time PCR and Western blot respectively. RESULTS: FOLR1 and HCP1/PCFT mRNA were lower in both plates of SGA and LGA placentas compared to AGA (p < 0.01) and RFC1 mRNA was lower only in CP (p < 0.02). RFC1 protein levels were lower in BP of SGA (p < 0.05) and LGA (p < 0.01), and FOLR1 protein levels were lower in CP of SGA (p < 0.02) and LGA (p < 0.01) groups compared to AGA. HCP1/PCFT protein levels remained unchanged in all groups. CONCLUSION: Placentas of SGA and LGA groups showed a reduced mRNA expression and protein levels of folate transporters, with some differences depending on the location within the placenta (BP or CP). This suggests the presence of specific placental regulation mechanisms in gene expression that may be associated to birth weight. PMID- 26907379 TI - Flow speed alters the apparent size and concentration of particles measured using NanoSight nanoparticle tracking analysis. AB - Nanoparticle tracking analysis (NTA) is commonly used to count and size nano sized particles. A sample loading pump can be used to analyse a larger sample volume, but it is unclear whether accuracy is affected. Using a NanoSight NS300 with the manufacturer-supplied pump, we examined synthetic silica and latex microspheres, liposomes and placental extracellular vesicles at different flow speeds. Analysis at flow speeds of 20 or 50 significantly reduced the measured concentration and mean/modal size of particles, particularly for mono-dispersed samples. We identify sample flow speed as a crucial instrument setting which should be reported in all studies that use NTA. PMID- 26907380 TI - Maternal obesity and sex-specific differences in placental pathology. AB - OBJECTIVE: Adverse effects of obesity have been linked to inflammation in various tissues, but studies on placental inflammation and obesity have demonstrated conflicting findings. We sought to investigate the influence of pregravid obesity and fetal sex on placental histopathology while controlling for diabetes and hypertension. METHODS: Placental histopathology focusing on inflammatory markers of a cohort of normal weight (BMI = 20-24.9) and obese (BMI >= 30) patients was characterized. Demographic, obstetric and neonatal variables were assessed. RESULTS: 192 normal and 231 obese women were included. Placental characteristics associated with obesity and fetal sex independent of diabetes and hypertension were placental disc weight >90(th) percentile, decreased placental efficiency, chronic villitis (CV), fetal thrombosis, and normoblastemia. Additionally, female fetuses of obese mothers had higher rates of CV and fetal thrombosis. Increasing BMI increased the risk of normoblastemia and CV. The final grade and extent of CV was significantly associated with obesity and BMI, but not fetal gender. Finally, CV was less common in large-for-gestation placentas. CONCLUSIONS: Maternal obesity results in placental overgrowth and fetal hypoxia as manifested by normoblastemia; it is also associated with an increased incidence of CV and fetal thrombosis, both more prevalent in female placentas. We have shown for the first time that the effect of maternal obesity on placental inflammation is independent of diabetes and hypertension, but significantly affected by fetal sex. Our data also point to the intriguing possibility that CV serves to normalize placental size, and potentially fetal growth, in the setting of maternal obesity. PMID- 26907381 TI - The relationship between human placental morphometry and ultrasonic measurements of utero-placental blood flow and fetal growth. AB - INTRODUCTION: Ultrasonic fetal biometry and arterial Doppler flow velocimetry are widely used to assess the risk of pregnancy complications. There is an extensive literature on the relationship between pregnancy outcomes and the size and shape of the placenta. However, ultrasonic fetal biometry and arterial Doppler flow velocimetry have not previously been studied in relation to postnatal placental morphometry in detail. METHODS: We conducted a prospective cohort study of nulliparous women in The Rosie Hospital, Cambridge (UK). We studied a group of 2120 women who had complete data on uterine and umbilical Doppler velocimetry and fetal biometry at 20, 28 and 36 weeks' gestational age, digital images of the placenta available, and delivered a liveborn infant at term. Associations were expressed as the difference in the standard deviation (SD) score of the gestational age adjusted ultrasound measurement (z-score) comparing the lowest and highest decile of the given placental morphometric measurement. RESULTS: The lowest decile of placental surface area was associated with 0.87 SD higher uterine artery Doppler mean pulsatility index (PI) at 20 weeks (95% CI: 0.68 to 1.07, P < 0.001). The lowest decile of placental weight was associated with 0.73 SD higher umbilical artery Doppler PI at 36 weeks (95% CI: 0.54 to 0.93, P < 0.001). The lowest decile of both placental weight and placental area were associated with reduced growth velocity of the fetal abdominal circumference between 20 and 36 weeks (both P < 0.001). CONCLUSION: Placental area and weight are associated with uterine and umbilical blood flow, respectively, and both are associated with fetal growth rate. PMID- 26907382 TI - Arterial endothelial cytokines guide extravillous trophoblast invasion towards spiral arteries; an in-vitro study with the trophoblast cell line ACH-3P and female non-uterine endothelial cells. AB - INTRODUCTION: Invasion of extravillous trophoblasts (EVT) is tightly linked to appropriate cell to cell contact as well as paracrine guidance of EVT by maternal uterine cells, conducted by a variety of locally expressed cytokines. Here we investigated the interaction of the first trimester trophoblast cell line ACH-3P with adult iliac arterial (AEC) and venous endothelial cells (VEC). METHODS: The impact of ACH-3P conditioned medium (Cdm), obtained at 2.5% and 21% oxygen, on endothelial cell viability (LDH-Assay) and network formation (Matrigel-Assay) was tested. We investigated cytokine expression of AEC- and VEC-Cdm and confirmed results with ELISA analysis, and investigated the influence of Cdm on ACH-3P proliferation and invasion. Additionally, direct co-culture experiments with ACH 3P and AEC on Matrigel were performed. A subset of experiments was verified with primary trophoblasts as well as with first trimester placenta in situ specimens. RESULTS: ACH-3P-Cdm significantly enhanced cell viability of AEC and VEC after 72 h. ACH-3P-Cdm at 2.5% oxygen stabilized endothelial network structures in Matrigel up to 24 h, similar to the effect of a direct co-culture of AEC and ACH 3P. AEC and VEC showed a similar pattern of secreted cytokines. However, elevated levels of cytokines secreted by AEC were found for GRO, IL-6, MMP-1 and uPAR. ELISA confirmed elevated concentrations of IL-6 and uPAR in AEC compared to VEC. ACH-3P and primary trophoblasts more likely invaded towards AEC-Cdm than towards VEC-Cdm. Addition of IL-6 to Cdm increased the invasion potential of both cell types. AEC- and VEC-Cdm reduced ACH-3P cell proliferation after 24 h of culture. IL-6 was highly expressed in uterine AEC compared to VEC as visualized by immunohistochemistry. DISCUSSION: The presented results clearly demonstrate that cytokines of both cell types, AEC and trophoblasts, differentially contribute to successful guidance and interaction in the process of trophoblast invasion. PMID- 26907383 TI - In-vivo stretch of term human fetal membranes. AB - INTRODUCTION: Fetal membranes (FM) usually fail prior to delivery during term labor, but occasionally fail at preterm gestation, precipitating preterm birth. To understand the FM biomechanical properties underlying these events, study of the baseline in-vivo stretch experienced by the FM is required. This study's objective was to utilize high resolution MRI imaging to determine in-vivo FM stretch. METHODS: Eight pregnant women (38.4 +/- 0.4wks) underwent abdominal pelvic MRI prior to (2.88 +/- 0.83d) caesarean delivery. Software was utilized to determine the total FM in-vivo surface area (SA) and that of its components: placental disc and reflected FM. At delivery, the SA of the disc and FM in the relaxed state were measured. In-vivo (stretched) to delivered SA ratios were calculated. FM fragments were then biaxially stretched to determine the force required to re-stretch the FM back to in-vivo SA. RESULTS: Total FM SA, in-vivo vs delivered, was 2135.51 +/- 108.47 cm(2) vs 842.59 +/- 35.86 cm(2); reflected FM was 1778.42 +/- 107.39 cm(2) vs 545.41 +/- 22.90 cm(2), and disc was 357.10 +/ 28.08 cm(2) vs 297.18 +/- 22.14 cm(2). The ratio (in-vivo to in-vitro SA) of reflected FM was 3.26 +/- 0.11 and disc was 1.22 +/- 0.10. Reflected FM re stretched to in-vivo SA generated a tension of 72.26 N/m, corresponding to approximate pressure of 15.4 mmHg. FM rupture occurred at 295.08 +/- 31.73 N/m corresponding to approximate pressure of 34 mmHg. Physiological SA was 70% of that at rupture. DISCUSSION: FM are significantly distended in-vivo. FM collagen fibers were rapidly recruited once loaded and functioned near the failure state during in-vitro testing, suggesting that, in-vivo, minimal additional (beyond physiological) stretch may facilitate rapid, catastrophic failure. PMID- 26907384 TI - Fetal-maternal nitrite exchange in sheep: Experimental data, a computational model and an estimate of placental nitrite permeability. AB - INTRODUCTION: Nitrite conveys NO-bioactivity that may contribute to the high flow, low-resistance character of the fetal circulation. Fetal blood nitrite concentrations depend partly on placental permeability which has not been determined experimentally. We aimed to extract the placental permeability-surface (PS) product for nitrite in sheep from a computational model. METHODS: An eight compartment computational model of the fetal-maternal unit was constructed (Matlab((r)) (R2013b (8.2.0.701), MathWorks Inc., Natick, MA). Taking into account fetal and maternal body weights, four variables (PS, the rate of nitrite metabolism within red cells, and two nitrite distribution volumes, one with and one without nitrite metabolism), were varied to obtain optimal fits to the experimental plasma nitrite profiles observed following the infusion of nitrite into either the fetus (n = 7) or the ewe (n = 8). RESULTS: The model was able to replicate the average and individual nitrite-time profiles (r(2) > 0.93) following both fetal and maternal nitrite infusions with reasonable variation of the four fitting parameters. Simulated transplacental nitrite fluxes were able to predict umbilical arterial-venous nitrite concentration differences that agreed with experimental values. The predicted PS values for a 3 kg sheep fetus were 0.024 +/- 0.005 l?min(-1) in the fetal-maternal direction and 0.025 +/- 0.003 l?min(-1) in the maternal-fetal direction (mean +/- SEM). These values are many fold higher than the reported PS product for chloride anions across the sheep placenta. CONCLUSION: The result suggests a transfer of nitrite across the sheep placenta that is not exclusively by simple diffusion through water-filled channels. PMID- 26907386 TI - Fetal asphyctic preconditioning in rats results in a preserved placental inflammatory phenotype at birth. AB - INTRODUCTION: Perinatal asphyxia (PA) is a major cause of neonatal mortality and morbidity. Research has shown that in rats fetal asphyxia (FA) can provoke neuroprotection against a subsequent more severe perinatal asphyctic insult. This is called fetal asphyctic preconditioning (PC). Our objective was to investigate alterations in the placental inflammatory phenotype associated with PC. METHODS: FA was induced in the rat at embryonic day 17 by reversibly clamping the uterine circulation and PA was induced at birth by submersion of the uterine horns in a saline bath for 19 min. The effect of PC was studied by inducing FA at E17, followed by PA at E21. Placental TNF-alpha, IL-1beta, IL-6 and IL-10 mRNA and protein levels were measured by qPCR and ELISA. RESULTS: IL-1beta mRNA increased in the labouring FA group, but IL-1beta protein decreased after both FA and PA. In the PC group, IL-1beta mRNA and protein levels were similar to controls. IL-6 protein increased 6 h after FA, however decreased 24 h after FA. IL-6 mRNA was higher in the labouring PA group. IL-10 protein decreased 24 h after FA. At birth, IL-10 mRNA increased in the PA group; however, IL-10 protein decreased in both the PA and the FA group. In the PC group, IL-10 mRNA and protein were similar to control levels. DISCUSSION: Depleted protein concentrations of IL-10 and IL-1beta after one single asphyctic insult were reversed after fetal asphyctic PC. In addition, PC placentas showed less up-regulation of IL-6 mRNA compared to the PA ones. This modulated placental inflammatory phenotype might contribute to the improved neonatal outcome showed after fetal asphyctic PC. PMID- 26907385 TI - Role of decidual CD14(+) macrophages in the homeostasis of maternal-fetal interface and the differentiation capacity of the cells during pregnancy and parturition. AB - OBJECTIVE: Decidual macrophages (dMPhis) have been implicated in fetal tolerance, but little information is known regarding their differentiation capacity and interactions with T cells. The present study aimed to investigate the immunological characteristics of dMPhis at mid and term pregnancy. METHODS: The dMPhis were analyzed for their phenotypes and cytokine production by flow cytometry and ELISA, respectively. The transendothelial trafficking model was implemented to allow the dMPhis to differentiate. The differentiated cells from dMPhis were also measured for their phenotypes and cytokine production with same methods. The capacity of dMPhis or the differentiated cells from dMPhis to stimulate allogeneic T lymphocyte proliferation was evaluated by T lymphocyte stimulation assays. T cell differentiation was determined by flow cytometry. RESULTS: The dMPhis in the mid-pregnancy (Mid-dMPhis) resembled the M2 phenotype. The differentiated cells from Mid-dMPhis had little stimulatory capacity on T cell proliferation and favored regulatory T cell differentiation. The dMPhis at term differentiated into dendritic (DC)-like cells, stimulating T cell activation, proliferation, and differentiation into IFN-gamma-producing T cellsdecidual CONCLUSIONS: The present study suggests that the differences in phenotypes and cytokine production between Mid- and Term-dMPhis relate to their different roles in the homeostasis of the maternal-fetal interface. Mid-dMPhis differentiate into DC-like cells with immunosuppressive properties, playing an important role in maintaining homeostasis required for a successful pregnancy. Term-dMPhis differentiate into DC-like cells with immunostimulatory properties, likely involved in the activation of labor. The different differentiation capacities of dMPhis in the varied pregnancy stages may be due to the placental microenvironment. PMID- 26907387 TI - The embryo-placental CD15-positive "vasculogenic zones" as a source of propranolol-sensitive pediatric vascular tumors. AB - OBJECTIVE: Propranolol-induced involution is a unique biological feature of some pediatric vascular tumors, for instance infantile hemangioma (IH), cerebral cavernoma or chorioangioma. Currently, the cellular origin of these distinct tumors is unclear. In this study, we tested the hypothesis that propranolol responsive vascular tumors are derived from common vessel-forming CD15 + progenitor cells which occur in early gestation. The aim of this study was to identify the tumor-relevant CD15 + progenitors at the early stages of embryo placental development. MATERIALS AND METHODS: Human embryo-placental units of 4-8 weeks gestation and pediatric vascular tumors were tested for expression of the tumor-relevant markers CD15, CD31 and CD34. RESULTS: Placental vessel-forming progenitors were characterized by immunostaining for CD15, CD31, and CD34. In embryonic tissue, a discontinuous CD15+/CD31+/CD34 + progenitors was detected in immature vessels of the skin, neural tube, spinal and cerebral meninges. Similarly, vessels in IH and chorioangioma exhibited a co-expression of CD15, CD31, and CD34. In contrast, the majority of embryonic vessels presented a CD31+/CD34+, but CD15-negative immunophenotypic pattern. DISCUSSION: Our results suggest the existence of a CD15+ "vasculogenic zones" in the embryo-placental unit as well as in IH and chorioangioma. A site-specific correlation between normal embryo-placental and tumoral vessel-forming CD15 + progenitors was demonstrated. CONCLUSION: Hence, site- and stage-specific CD15 + progenitors of vascular wall could be considered as propronalol-sensitive targets and source of pre- and postnatal vascular tumors. We propose, that the CD15+ "vasculogenic zones" are a site-specific reserve of multi-lineage progenitors that could be recruited in pre- and postnatal emergency situations. PMID- 26907388 TI - Relation of FTO gene variants to fetal growth trajectories: Findings from the Southampton Women's survey. AB - INTRODUCTION: Placental function is an important determinant of fetal growth, and fetal growth influences obesity risk in childhood and adult life. Here we investigated how FTO and MC4R gene variants linked with obesity relate to patterns of fetal growth and to placental FTO expression. METHODS: Southampton Women's Survey children (n = 1990) with measurements of fetal growth from 11 to 34 weeks gestation were genotyped for common gene variants in FTO (rs9939609, rs1421085) and MC4R (rs17782313). Linear mixed-effect models were used to analyse relations of gene variants with fetal growth. RESULTS: Fetuses with the rs9939609 A:A FTO genotype had faster biparietal diameter and head circumference growth velocities between 11 and 34 weeks gestation (by 0.012 (95% CI 0.005 to 0.019) and 0.008 (0.002-0.015) standard deviations per week, respectively) compared to fetuses with the T:T FTO genotype; abdominal circumference growth velocity did not differ between genotypes. FTO genotype was not associated with placental FTO expression, but higher placental FTO expression was independently associated with larger fetal size and higher placental ASCT2, EAAT2 and y + LAT2 amino acid transporter expression. Findings were similar for FTO rs1421085, and the MC4R gene variant was associated with the fetal growth velocity of head circumference. DISCUSSION: FTO gene variants are known to associate with obesity but this is the first time that the risk alleles and placental FTO expression have been linked with fetal growth trajectories. The lack of an association between FTO genotype and placental FTO expression adds to emerging evidence of complex biology underlying the association between FTO genotype and obesity. PMID- 26907389 TI - A method for isolating and culturing placental cells from failed early equine pregnancies. AB - Early pregnancy loss occurs in 6-10% of equine pregnancies making it the main cause of reproductive wastage. Despite this, reasons for the losses are known in only 16% of cases. Lack of viable conceptus material has inhibited investigations of many potential genetic and pathological causes. We present a method for isolating and culturing placental cells from failed early equine pregnancies. Trophoblast cells from 18/30 (60%) failed equine pregnancies of gestational ages 14-65 days were successfully cultured in three different media, with the greatest growth achieved for cells cultured in AmnioChromeTM Plus. Genomic DNA of a suitable quality for molecular assays was also isolated from 29/30 of these cases. This method will enable future investigations determining pathologies causing EPL. PMID- 26907391 TI - Tailoring of the Brillouin gain for on-chip widely tunable and reconfigurable broadband microwave photonic filters. AB - An unprecedented Brillouin gain of 44 dB in a photonic chip enables the realization of broadly tunable and reconfigurable integrated microwave photonic filters. More than a decade bandwidth reconfigurability from 30 up to 440 MHz, with a passband ripple <1.9 dB is achieved by tailoring the Brillouin pump. The filter central frequency is continuously tuned up to 30 GHz with no degradation of the passband response, which is a major improvement over electronic filters. Furthermore, we demonstrate pump tailoring to realize multiple bandpass filters with different bandwidths and central frequencies, paving the way for multiple on chip microwave filters and channelizers. PMID- 26907390 TI - Additive cardioprotection by pharmacological postconditioning with hydrogen sulfide and nitric oxide donors in mouse heart: S-sulfhydration vs. S nitrosylation. AB - Hydrogen sulfide (H2S), as a gaseous signalling molecule, has been found to play important roles in postconditioning (PostC)-induced cardioprotection. Similar to nitric oxide (NO)-mediated protein S-nitrosylation (SNO), recent studies suggest that H2S could regulate protein function through another redox-based post translational modification on protein cysteine residue(s), i.e. S-sulfhydration (SSH). In this study, we examined whether there are changes in protein SSH associated with cardioprotection induced by treatment with H2S on reperfusion. In addition, we also examined whether there is cross talk between H2S and NO. Compared with control, treatment on reperfusion with NaHS (H2S donor, 100 umol/L) significantly reduced post-ischaemic contractile dysfunction and infarct size. A comparable cardioprotective effect could be also achieved by reperfusion treatment with SNAP (NO donor, 10 umol/L). Interestingly, simultaneous reperfusion with both donors had an additive protective effect. In addition, C PTIO (NO scavenger, 20 umol/L) eliminated the protection induced by NaHS and also the additive protection by SNAP + NaHS together. Using a modified biotin switch method, we observed a small increase in SSH following NaHS treatment on reperfusion. We also found that NaHS treatment on reperfusion increases SNO to a level comparable to that with SNAP treatment. In addition, there was an additive increase in SNO but not SSH when SNAP and NaHS were added together at reperfusion. Thus, part of the benefit of NaHS is an increase in SNO, and the magnitude of the protective effect is related to the magnitude of the increase in SNO. PMID- 26907392 TI - Novel porous fiber based on dual-asymmetry for low-loss polarization maintaining THz wave guidance. AB - In this Letter, we suggest a novel kind of porous-core photonic crystal fiber (PCF) (to the best of our knowledge) for efficient transportation of polarization maintaining (PM) terahertz (THz) waves. We introduce an asymmetry in both the porous-core and the porous-cladding of the structure to achieve an ultra-high birefringence. Besides, only circular air holes have been used to represent the structure, which makes the fiber remarkably simple. The transmission characteristics have been numerically examined based on an efficient finite element method (FEM). The numerical results confirm a high birefringence of ~0.045 and a very low effective absorption loss of 0.08 cm(-1) for optimal design parameters at 1 THz. We have also thoroughly investigated some important modal properties such as bending loss, power fraction, dispersion, and fabrication possibilities to completely analyze the structure's usability in a multitude of THz appliances. Moreover, physical insights of the proposed fiber have also been discussed. PMID- 26907393 TI - Scattering of entangled two-photon states. AB - We consider the scattering of entangled two-photon states from collections of small particles. We also study the related Mie problem of scattering from a sphere. In both cases, we calculate the entropy of entanglement and investigate the influence of the entanglement of the incident field on the entanglement of the scattered field. PMID- 26907394 TI - Broadband azimuthal polarization conversion using gold nanowire enhanced step index fiber. AB - We show broadband azimuthal polarization state conversion using an entirely connectorized step-index fiber with a central gold nanowire. This device provides broadband polarization discrimination of the low-loss TE01 fiber mode with respect to all other modes, and converts light into the azimuthal polarization state, resulting in a high beam quality and an azimuthal conversion efficiency of 37%. The device is monolithically integrated into fiber circuitry, representing a new platform for plasmonics and fiber optics and enabling important applications in super-resolution microscopy, laser tweezing, and plasmonic superfocussing. PMID- 26907395 TI - Higher order mode suppression in high-Q anomalous dispersion SiN microresonators for temporal dissipative Kerr soliton formation. AB - High-Q silicon nitride (SiN) microresonators enable optical Kerr frequency comb generation on a photonic chip and have recently been shown to support fully coherent combs based on temporal dissipative Kerr soliton formation. For bright soliton formation, it is necessary to operate SiN waveguides in the multimode regime in order to produce waveguide induced anomalous group velocity dispersion. However, this regime can lead to local disturbances of the dispersion due to avoided crossings caused by coupling between different mode families and, therefore, prevent the soliton formation. Here, we demonstrate that a single-mode "filtering" section inside high-Q resonators enables efficiently suppression of avoided crossings, while preserving high quality factors (Q~10(6)). We verify the approach by demonstrating single soliton formation in SiN resonators with a filtering section. PMID- 26907396 TI - Impact of the Coulomb interaction on the Franz-Keldysh effect in high-current photodetectors. AB - The Franz-Keldysh effect has been recognized as the largest contributor to oscillations in the responsivity of high-current photodetectors as a function of the applied bias or the incident light wavelength and to device nonlinearity. Prior work only considered the effect of the electric field without considering the Coulomb interaction. We show that it is not possible to obtain agreement with experiments at all optical wavelengths without including this effect in the effective mass equation. We find the maxima and minima in the absorption of the applied electric field shift when the Coulomb interaction is included. We then use the calculated absorption with the drift-diffusion equations to calculate the responsivity in a partially depleted absorber (PDA) photodetector, and we obtain excellent agreement with experiments at all biases and optical wavelengths. PMID- 26907397 TI - Calibration-free measurement of high-speed Mach-Zehnder modulator based on low frequency detection. AB - A calibration-free electrical method is demonstrated for measuring the frequency response of high-speed Mach-Zehnder modulators (MZMs) based on low-frequency detection. The method achieves the high-frequency modulation index and half-wave voltage measurement of MZMs by the low-frequency electrical spectrum analysis of the two-tone and bias-modulated optical signal. Moreover, it eliminates the need for correcting the responsivity fluctuation in the photodetector through setting a specific frequency relationship between the two-tone and bias modulation. Both absolute and relative frequency response of MZMs are experimentally measured with our method and compared with those obtained with conventional methods to check for consistency. PMID- 26907398 TI - Enhanced upconversion of NaYF4:Er3+/Yb3+ phosphors prepared via the rapid microwave-assisted hydrothermal route at low temperature: phase and morphology control. AB - Monophasic NaYF4:Er(3+)/Yb(3+) crystals were synthesized via the microwave assisted hydrothermal route at 180 degrees C. Microwave heating during the hydrothermal process substantially reduces the duration of reaction for the formation of cubic-NaYF4:Er(3+)/Yb(3+) nanocrystals from 6 h to 30 min. As the duration of the reaction increases, cubic-NaYF4:Er(3+)/Yb(3+) nanocrystals are transformed to uniform hexagonal-NaYF4:Er(3+)/Yb(3+) microprisms because of the enhanced reaction kinetics. Bright upconverted emission from the NaYF4:Er(3+)/Yb(3+) crystal, obtained by the efficient two-photon excitation, is related to crystal structure and morphology. The hexagonal microprisms exhibit better upconversion and are employed in security applications. PMID- 26907399 TI - Spatial resolution-preserving retroreflection for gas-phase laser scattering measurements in turbulent flames using a phase-conjugate mirror. AB - This Letter reports on the demonstration of a stimulated Brillouin-scattering phase conjugate mirror (SBS-PCM) for multipass laser-based scattering measurements in turbulent flames. Retroreflective measurements using the SBS-PCM show substantial improvements in spatial-resolution preservation as compared to measurements using a conventional mirror as a multipass reflector. The results using the SBS-PCM indicate an insensitivity to large index-of-refraction gradients and preservation of the original spatial resolution as defined by the laser beam under reacting flow conditions. This approach offers the possibility of increasing signal-to-noise ratios within low-signal gas-phase measurements such as Rayleigh and Raman scattering. PMID- 26907400 TI - High-resolution magnetic field imaging with a nitrogen-vacancy diamond sensor integrated with a photonic-crystal fiber. AB - We demonstrate high-resolution magnetic field imaging with a scanning fiber-optic probe which couples nitrogen-vacancy (NV) centers in diamond to a high-numerical aperture photonic-crystal fiber integrated with a two-wire microwave transmission line. Magnetic resonance excitation of NV centers driven by the microwave field is read out through optical interrogation through the photonic-crystal fiber to enable high-speed, high-sensitivity magnetic field imaging with sub 30 MUm spatial resolution. PMID- 26907401 TI - Bidirectional fiber-wireless and fiber-VLLC transmission system based on an OEO based BLS and a RSOA. AB - A bidirectional fiber-wireless and fiber-visible-laser-light-communication (VLLC) transmission system based on an optoelectronic oscillator (OEO)-based broadband light source (BLS) and a reflective semiconductor optical amplifier (RSOA) is proposed and experimentally demonstrated. Through an in-depth observation of such bidirectional fiber-wireless and fiber-VLLC transmission systems, good bit error rate performances are obtained over a 40 km single-mode fiber and a 10 m RF/optical wireless transport. Such a bidirectional fiber-wireless and fiber-VLLC transmission system is an attractive option for providing broadband integrated services. PMID- 26907402 TI - Coupling dynamics of 1D surface plasmon polaritons in hybrid graphene systems. AB - We describe the coupling dynamics of one-dimensional surface plasmon polaritons supported by a pair of hetero-junctions between two-dimensional media. We first discuss the unique symmetry properties of the supermodes of such structures, and then we exploit the possibility of electrically tuning the conductivity of graphene to demonstrate tailoring and manipulation of light propagation in a graphene/graphene platform. PMID- 26907403 TI - Tip size dependence of passive near-field microscopy. AB - We improve the spatial resolution and investigate the tip-sample coupling in a passive scattering-type scanning near-field optical microscope (s-SNOM), which probes thermally excited surface waves without any external light source. We study the spatial resolution, the intensity, and the decay behavior of the thermally excited near-field signals with different radii of curvatures of tungsten-tip apexes. We also study the tip size dependence of the interference pattern in the far-field region. The spatial resolution is closely related to the tip size, but the decay behavior of the near field is unrelated. These results suggest that the strength of the tip-sample coupling is unrelated to the tip size in the passive s-SNOM. We propose a theoretical model able to interpret the experimental data for the passive s-SNOM. PMID- 26907404 TI - Rovibrational hybrid fs/ps CARS using a volume Bragg grating for N2 thermometry. AB - Coherent anti-Stokes Raman scattering (CARS) spectra of N2 in the hybrid femtosecond/picosecond regime have been recorded with 0.7 cm(-1) resolution. The Q-branch rovibrational structure has been resolved, making it suitable for gas phase simultaneous rotational and vibrational thermometry applications. Resolving this spectral structure requires synchronization of a narrowband picosecond probe pulse with a broadband femtosecond pair of pump and Stokes pulses. It is achieved using a single femtosecond ytterbium-laser source and a volume Bragg grating in a compact experimental arrangement. PMID- 26907405 TI - 250 W average power, 100 kHz repetition rate cryogenic Yb:YAG amplifier for OPCPA pumping. AB - A cryogenically cooled, bulk Yb:YAG, four-pass amplifier delivering up to 250 W average power at 100 kHz repetition rate is reported. The 2.5 mJ amplified optical pulses show a sub-20 ps duration before temporal compression and a spectrum supporting a transform-limited duration of 3.6 ps. The power instabilities were measured to be <0.5% rms over 30 min at full power, and the spatial intensity profile showed a flat-top distribution and near diffraction limited beam quality. This compact amplifier is an ideal source for pumping either near-IR or mid-IR optical parametric chirped pulse amplifiers. PMID- 26907406 TI - Optimization of the split-spectrum amplitude-decorrelation angiography algorithm on a spectral optical coherence tomography system: erratum. AB - An erratum is presented to include conflict of interest disclosures that were unintentionally left out of our recent Letter [Opt. Lett.40, 2305 (2015)10.1364/OL.40.002305OPLEDP0146-9592]. PMID- 26907407 TI - High-resolution wavefront shaping with a photonic crystal fiber for multimode fiber imaging. AB - We demonstrate that a high-numerical-aperture photonic crystal fiber allows lensless focusing at an unparalleled resolution by complex wavefront shaping. This paves the way toward high-resolution imaging exceeding the capabilities of imaging with multi-core single-mode optical fibers. We analyze the beam waist and power in the focal spot on the fiber output using different types of fibers and different wavefront shaping approaches. We show that the complex wavefront shaping technique, together with a properly designed multimode photonic crystal fiber, enables us to create a tightly focused spot on the desired position on the fiber output facet with a subwavelength beam waist. PMID- 26907408 TI - Spectral properties and highly efficient continuous-wave laser operation in Nd doped Sr(1-x)Y(x)F(2+x) crystals. AB - Spectral properties of Nd:Sr(1-x)Y(x)F(2+x) crystals were investigated. Compared with Nd:SrF2, the spectral parameters of Nd:Sr(1-x)Y(x)F(2+x) (x=0.05,0.1) were altered in a large scale. LD-pumped true CW laser has been demonstrated in the crystals. The slope efficiency up to 43.5% in 0.43% Nd:Sr0.95Y0.05F2.05 was achieved. The system is a promising candidate for highly efficient lasers. PMID- 26907409 TI - 50 MUm core diameter Yb3+Al3+/F- codoped silica fiber with M2<1.1 beam quality. AB - This paper reports, for the first time to our best knowledge, a nearly diffraction-limited output in a Yb(3+)/Al(3+)/F(-) codoped double cladding silica fiber with a 50 MUm core diameter and 0.02 core NA. The core glass with a diameter >6 mm was fabricated through solgel process combined with high temperature sintering. Laser performances of this fiber at different bend diameters were studied. The mean M2<1.1 in this 50 MUm core diameter fiber was achieved at a bend diameter of 0.35 m. The core glass with the refractive index nearly equal to pure silica glass is suitable for the fiber design, such as large mode-area photonic crystal fiber. PMID- 26907410 TI - Spectral fusing Gabor domain optical coherence microscopy. AB - Gabor domain optical coherence microscopy (GD-OCM) is one of many variations of optical coherence tomography (OCT) techniques that aims for invariant high resolution across a 3D field of view by utilizing the ability to dynamically refocus the imaging optics in the sample arm. GD-OCM acquires multiple cross sectional images at different focus positions of the objective lens, and then fuses them to obtain an invariant high-resolution 3D image of the sample, which comes with the intrinsic drawback of a longer processing time as compared to conventional Fourier domain OCT. Here, we report on an alternative Gabor fusing algorithm, the spectral-fusion technique, which directly processes each acquired spectrum and combines them prior to the Fourier transformation to obtain a depth profile. The implementation of the spectral-fusion algorithm is presented and its performance is compared to that of the prior GD-OCM spatial-fusion approach. The spectral-fusion approach shows twice the speed of the spatial-fusion approach for a spectrum size of less than 2000 point sampling, which is a commonly used spectrum size in OCT imaging, including GD-OCM. PMID- 26907411 TI - Multiplexed off-axis holography using a transmission diffraction grating. AB - This Letter presents a novel multiplexed off-axis holographic microscope that makes use of a 1D holographic grating. The grating creates multiple object waves and projects four of them to the imaging sensor. The object waves then interfere with the reference wave at the imaging sensor, so that a multiplexed hologram is created. This approach retrieves the amplitude and phase profiles of four imaging areas with a single-exposure hologram, which greatly increases the field of view of an off-axis holographic microscope. The experimental results with the resolution target USAF 1951 T-22 and a slide of paramecia are shown to demonstrate the system's ability without sacrificing the resolution of the microscope objective. PMID- 26907412 TI - Random sources for beams with azimuthal intensity variation. AB - The structure of the degree of coherence of wide-sense statistically stationary planar sources radiating far fields with intensity patterns with azimuthal dependence is determined, to the best of our knowledge, for the first time. The Fourier series basis is used in decomposing arbitrary far-field intensity for obtaining the azimuthal modes, which are shown to correspond to the spatial frequency components of the source degree of coherence. The far fields with azimuthal structure can be produced experimentally with the help of spatial light modulators. PMID- 26907413 TI - High contrast circular grating reflector on silicon-on-insulator platform. AB - A compact circular high contrast grating (HCG) reflector with a footprint of only 4.03 MUm*4.32 MUm on 220 nm silicon-on-insulator (SOI) platform is proposed and experimentally demonstrated. The proposed device breaks the high wavelength selectivity limitation for the conventional grating reflectors on a thin SOI platform by using the circular structure in a compact region. In addition, the device provides a high polarization selectivity over a wide wavelength range which is useful for applications such as tunable laser cavities and resonators to provide wide tuning range and high polarization stability. The circular structure based HCG reflector has an ultra-wide operational bandwidth (Deltalambda) of over 385 nm with the center wavelength (lambda) set at 1550 nm, providing a Deltalambda/lambda=24.83%. An average reflectance high of 94.15% is observed from 1525 to 1610 nm in the experimental measurement. The polarization extinction ratio is greater than 13 dB over the entire measured wavelength range. PMID- 26907414 TI - Experimental implementations of 2D IR spectroscopy through a horizontal pulse shaper design and a focal plane array detector. AB - Aided by advances in optical engineering, two-dimensional infrared spectroscopy (2D IR) has developed into a promising method for probing structural dynamics in biophysics and material science. We report two new advances for 2D IR spectrometers. First, we report a fully reflective and totally horizontal pulse shaper, which significantly simplifies alignment. Second, we demonstrate the applicability of mid-IR focal plane arrays (FPAs) as suitable detectors in 2D IR experiments. FPAs have more pixels than conventional linear arrays and can be used to multiplex optical detection. We simultaneously measure the spectra of a reference beam, which improves the signal-to-noise by a factor of 4; and two additional beams that are orthogonally polarized probe pulses for 2D IR anisotropy experiments. PMID- 26907416 TI - Highly sensitive refractive index sensing by fast detuning the critical coupling condition of slot waveguide ring resonators. AB - We experimentally investigate refractive index sensing in silicon slot waveguide ring resonators by the detection of the giant shift of the ring transmission spectrum envelope enabled by the following specific conditions: the slot waveguide cross section as well as the ring couplers have been designed to lead to a V-shaped microring resonator spectrum modulated by the classical frequency comb and exhibiting quality factor peaks of 2000-6000 around lambda=1.5 MUm. By tracking the spectrum envelope wavelength shift, sensitivity up to S=1,300 nm per refraction index unit (RIU) is reported when the slots are filled by liquids with refraction index values close to 1.33. PMID- 26907415 TI - Nano-optical conveyor belt with waveguide-coupled excitation. AB - We propose a plasmonic nano-optical conveyor belt for peristaltic transport of nano-particles. Instead of illumination from the top, waveguide-coupled excitation is used for trapping particles with a higher degree of precision and flexibility. Graded nano-rods with individual dimensions coded to have resonance at specific wavelengths are incorporated along the waveguide in order to produce spatially addressable hot spots. Consequently, by switching the excitation wavelength sequentially, particles can be transported to adjacent optical traps along the waveguide. The feasibility of this design is analyzed using three dimensional finite-difference time-domain and Maxwell stress tensor methods. Simulation results show that this system is capable of exciting addressable traps and moving particles in a peristaltic fashion with tens of nanometers resolution. It is the first, to the best of our knowledge, report about a nano-optical conveyor belt with waveguide-coupled excitation, which is very important for scalability and on-chip integration. The proposed approach offers a new design direction for integrated waveguide-based optical manipulation devices and its application in large scale lab-on-a-chip integration. PMID- 26907417 TI - Design of bandpass filters composed of dielectric layers separated by gratings of strip conductors. AB - We derive the design formulas for novel multilayer bandpass filters in which every dielectric layer (resonator) is separated from the adjacent layer or external medium by a grating of strip conductors. Every grating acts as a semi reflecting mirror. Such novel filters have wide stop bands compared to conventional filters with multilayer dielectric mirrors between resonators at the same passband width. The parameters of the lowpass, lumped-element prototype filter, as well as the theory of resonator-coupling coefficients, are considered in our approach. The computed frequency response of the fifth-order Chebyshev filter that was synthesized using the proposed formulas is also presented. PMID- 26907418 TI - Watt-level passively Q-switched Er:Lu2O3 laser at 2.84 MUm using MoS2. AB - Efficient diode-pumped passively Q-switched Er:Lu2O3 laser operation at 2.84 MUm was realized. A few-layer MoS2 nanosheet film on a YAG substrate, was fabricated and employed as saturable absorber (SA) in a short plane-plane cavity. Under an absorbed diode laser pump power of 7.61 W, an average output power of 1.03 W was generated with a pulse duration of 335 ns and a repetition rate of 121 kHz, resulting in a pulse energy of 8.5 MUJ. PMID- 26907419 TI - Fano-resonance-based ultra-high-resolution ratio-metric wavelength monitor on silicon. AB - An integrated ultra-high-resolution ratio-metric wavelength monitor (RMWM) with compact size based on slope tunable Fano resonance is demonstrated on silicon. The Fano resonance is generated by adding an asymmetric microring inside and coupling with the outer ring to produce a nonlinear phase shift. The slope tunability is achieved by controlling the microheaters to adjust the phase condition. Two asymmetric embedded microring resonators (AEMR) are functioned as edge filters and designed to achieve an "X-type" spectral response in a particular wavelength range. An ultra-high resolution of 0.8 pm in a 0.47 nm wide wavelength range is experimentally demonstrated. This device could be applied in on-chip high-sensitivity wavelength monitoring sensing. PMID- 26907420 TI - Actively mode-locked all fiber laser with cylindrical vector beam output. AB - We demonstrated an all fiber actively mode-locked laser that emits a cylindrical vector beam. An intra-cavity few-mode fiber Bragg grating inscribed in a short section of four-mode fiber is employed to provide mode selection and spectrum filtering functions. Mode coupling is achieved by offset splicing between the single-mode fiber and the four-mode fiber in the laser cavity. A LiNbO3 Mach Zehnder modulator is used to achieve active mode-locking in the laser. The laser operates at 1547 nm with 30 dB spectrum width of 0.2 nm. The mode-locked pulses have a duration of 2 ns and repetition of 12.06 MHz. Through adjusting the polarization state in the laser cavity, both radially and azimuthally polarized beams have been obtained with high mode purity. PMID- 26907421 TI - Tuning whispering gallery lasing modes from polymer fibers under tensile strain. AB - Wavelength tuning of whispering gallery lasing modes has been observed from Rhodamine-B-doped polymer fibers under tensile strain. Good quality whispering gallery lasing modes are produced from both solid and hollow fibers by transverse optical pumping. The lasing modes are shifted linearly toward the shorter wavelength side when the fiber is elongated in the axial direction. Compared with solid fiber, the lasing modes of hollow fiber can be tuned over the entire gain spectrum with a tuning range of ~5 nm. It is found that the tuning of the lasing modes of hollow fiber is reversible. PMID- 26907422 TI - Formation of single-mode laser in transverse plane of perovskite microwire via micromanipulation. AB - The synthesized perovskites are randomly distributed and their optical properties are fixed after synthesis. Here we demonstrate the tailoring of lasing properties of perovskite microwire via micromanipulation. One microwire has been lifted by a tungsten probe and repositioned on a nearby perovskite microplate with one end suspended in air. Consequently, the conventional Fabry-Perot lasers are completely suppressed and a single laser peak has been observed. The numerical calculations reveal that the single-mode laser is formed by the whispering gallery mode in the transverse plane of microwire. Our research provides a simple way to tailor the properties of microwire postsynthesis. PMID- 26907423 TI - Watt-level erbium-doped all-fiber laser at 3.44 MUm. AB - We demonstrate a 3.44 MUm all-fiber laser emitting a maximum of 1.5 W at room temperature, the highest continuous power ever generated from a mid-IR fiber oscillator clearly beyond 3 MUm. The laser operates on the 4F(9/2)->4I(9/2) transition of erbium-doped fluoride glasses and relies on a dual pumping scheme at 974 and 1976 nm. By combining a dichroic mirror deposited on the input fiber tip and a fiber Bragg grating as an output coupler, a stable laser emission is produced with a FWHM bandwidth of less than 0.6 nm. The laser cavity has an efficiency of 19% with respect to the launched pump power at 1976 nm and no saturation is observed provided 974 nm co-pumping is sufficient. The joint effect of the two pumps is also investigated. PMID- 26907424 TI - Magnetoplasmonic isolators utilizing the nonreciprocal phase shift. AB - We propose a long-range magnetoplasmonic waveguide structure, based on cerium substituted yttrium iron garnets, that is capable of achieving a useful pi/2 nonreciprocal phase shift within one propagation length. Incorporating this plasmonic geometry into a Mach-Zehnder interferometer allows for the implementation of an efficient, integrable isolator scheme with an insertion loss of 2.51 dB and an extinction ratio of 22.82 dB. With a small footprint of 6.4*10( 3) mm(2) and nanoscale waveguide dimensions, we envision this device to be a key building block in the development of nanoplasmonic integrated circuitry. PMID- 26907425 TI - Tunable Anderson localization in disorder graphene sheet arrays. AB - We study the electromagnetic wave propagating in coupled monolayer graphene waveguide arrays (CMGWAs). It is found that Anderson localization exists when the disorder in the coupling strength between adjacent waveguides is introduced. We find that changing the statistical parameters of the disorder coupling strength between waveguides can be used to tailor the properties of the Anderson localization modes in the strong coupling region which is beyond the coupled-mode theory. Benefiting from the electric tunable surface conductivity, we further demonstrate via the full vectorial simulation that the localization strength of the Anderson localized mode can be manipulated by changing the applied gate voltage on the CMGWAs. Our results might facilitate the manipulation of electromagnetic wave propagation in the coupled waveguide array system. PMID- 26907426 TI - Short cavity-length random fiber laser with record power and ultrahigh efficiency. AB - We report the result of achieving a random fiber laser (RFL) with record 200-W level power output. The highest output power is realized by a simple 120 m long cavity at a working wavelength of 1173 nm while pumping at 1120 nm. The maximum observed optical-to-optical efficiency reaches ~89%, which is believed to be the highest value ever reported for RFLs. In addition, numerical calculations on different order Raman Stokes wave thresholds based on the theoretical model are carried out for comparison with the experimental data. The presented work effectively advances the power scalability, and the numerical model well describes the lasing thresholds in such short cavity RFLs. PMID- 26907427 TI - Degenerate four-wave mixing in a silica hollow bottle-like microresonator. AB - A hollow, bottle-like microresonator (BLMR) was fabricated from a microcapillary with a nearly parabolic profile. From simulations at 1.55 MUm the fundamental bottle mode is shown to be in the anomalous dispersion regime, while the conventional whispering gallery mode, confined to the center of the BLMR, is in the normal dispersion regime. Therefore, we have experimentally shown that, for a BLMR with a diameter of 102 um, degenerate four-wave mixing can only be observed by judicious selection of the tapered fiber coupling position. Dispersion tuning in such a system is also briefly discussed theoretically. BLMRs are promising devices for the implementation of sparsely distributed, widely spanned frequency combs at the telecommunications C-band. PMID- 26907428 TI - High Q factor InP photonic crystal nanobeam cavities on silicon wire waveguides. AB - High-quality (Q) factor indium phosphide (InP)-based 1D photonic crystal nanobeam cavities are fabricated on silicon on insulator waveguides. Through the optimization of the fabrication process, the intrinsic Q factor of these fully encapsulated nanocavities is demonstrated to attain values higher than 100,000. Experimental and numerical investigations are carried out on the impact, on the Q factor, of the strength of the evanescent wave coupling between the cavity and the waveguide. We reveal that this coupling can result in a modification of the electromagnetic field distribution in the resonant mode, which gives rise up to a factor 4 reduction in the intrinsic Q factor for the structures under study. PMID- 26907429 TI - Ring dark and antidark solitons in nonlocal media. AB - Ring dark and antidark solitons in nonlocal media are found. These structures have, respectively, the form of annular dips or humps on top of a stable CW background, and exist in a weak or strong nonlocality regime, defined by the sign of a characteristic parameter. It is demonstrated analytically that these solitons satisfy an effective cylindrical Kadomtsev-Petviashvili (aka Johnson's) equation and, as such, can be written explicitly in closed form. Numerical simulations show that they propagate undistorted and undergo quasi-elastic collisions, attesting to their stability properties. PMID- 26907430 TI - Hybrid distributed acoustic and temperature sensor using a commercial off-the shelf DFB laser and direct detection. AB - We demonstrate a hybrid distributed acoustic and temperature sensor (DATS) using a commercial off-the-shelf (COTS) distributed feedback (DFB) laser, a single-mode optical fiber, and a common receiver block. We show that the spectral and frequency noise characteristics of the laser, combined with a suitable modulation scheme, ensure the inter-pulse incoherence and intra-pulse coherence conditions required for exploiting the fast denoising benefits of cyclic Simplex pulse coding in the hybrid measurement. The proposed technique enables simultaneous, distributed measurement of vibrations and temperature, with key industrial applications in structural health monitoring and industrial process control systems. The sensor is able to clearly identify a 500 Hz vibration at 5 km distance along a standard single-mode fiber and simultaneously measure the temperature profile along the same fiber with a temperature resolution of less than 0.5 degrees C with 5 m spatial resolution. PMID- 26907431 TI - Plasmon-induced transparency in binary arrays of ultrathin metal stripes for narrow-band transmission. AB - Transversely localized resonance of antisymmetric-bound surface plasmons (ab-SP) at ultrathin metal stripes in a subwavelength array suppresses optical transmission in a broadband. Here, asymmetric binary arrays of ultrathin metal stripes are proposed to introduce a narrow transmission peak in the stop-band (i.e., plasmon-induced transparency), based on destructive interference of antisymmetrically excited ab-SP resonance modes at the neighboring binary metal stripes. The phenomenon is numerically demonstrated and explained with a mesoscopic model, in which mesoscopic interaction processes are abstracted as different transmission channels to cooperatively result in the narrow peak in a broad transmission valley. In spite of the ultrathin feature of the structure for convenience in fabrication, its excellent performance facilitates potential applications. PMID- 26907432 TI - Simultaneous frequency stabilization, wavelength multiplexing and improvement of beam quality using a self-optimizing external cavity diode laser. AB - The combination of a dense wavelength division multiplexer based on volume Bragg gratings (VBGs) and a subsequent feedback mirror forms an efficient single-stage frequency stabilization and multiplexing system. The laser emission of the connected diode laser sources is automatically forced to amplify the wavelengths with the maximum feedback and the minimum losses, respectively. Therefore, different transversal modes of a single emitter may be linked to different wavelength regions that fulfill the Bragg conditions of the VBGs with high efficiency. We demonstrate a multiplexing system with a channel spacing of 1.5 nm and an optical efficiency of 86%, up to 90% being feasible with modifications. The emission bandwidth of the diode laser single emitters is reduced to <300 pm. Due to transversal mode selection, the lateral beam quality factor M2 of the single emitters decreases by a factor of 1.4 on average, compared to the free running sources. PMID- 26907433 TI - Three-dimensional joint transform correlator cryptosystem. AB - We introduce for the first time, to the best of our knowledge, a three dimensional experimental joint transform correlator (JTC) cryptosystem allowing the encryption of information for any 3D object, and as an additional novel feature, a second 3D object plays the role of the encoding key. While the JTC architecture is normally used to process 2D data, in this work, we envisage a technique that allows the use of this architecture to protect 3D data. The encrypted object information is contained in the joint power spectrum. We register the key object as a digital off-axis Fourier hologram. The encryption procedure is done optically, while the decryption is carried out by means of a virtual optical system, allowing for flexible implementation of the proposal. We present experimental results to demonstrate the validity and feasibility of the method. PMID- 26907434 TI - Graphene-controlled fiber Bragg grating and enabled optical bistability. AB - We report a graphene-assisted all-optical control of a fiber Bragg grating (FBG), which enables in-fiber optical bistability and switching. With an optical pump, a micro-FBG wrapped by graphene evolves into chirped and phase-shifted FBGs, whose characteristic wavelengths and bandwidths could be controlled by the pump power. Optical bistability and multistability are achieved in the controlled FBG based on a shifted Bragg reflection or Fabry-Perot-type resonance, which allow the implementation of optical switching with an extinction ratio exceeding 20 dB and a response time in tens of milliseconds. PMID- 26907435 TI - Fabrication and analysis of single-crystal KTiOPO4 films with thicknesses in the micrometer range. AB - Single-crystal potassium titanyl phosphate (KTiOPO4, KTP) films with thicknesses less than 5 MUm are obtained by using helium (He) implantation combined with ion beam-enhanced etching. A heavily damaged layer created by a 4*10(16) cm(-2) fluence of 2 MeV He implantation is removed by means of wet chemical etching in hydrofluoric acid (HF). Thus, free-standing films of KTP with thicknesses in the range of 3-5 MUm are obtained. The etching rate can be adjusted over a wide range by choosing temperature and HF concentration, as well as annealing conditions. Sharp etching edges and the smooth surface of the film indicate that a high selective-etching rate is achieved in the damaged layer, and the remaining part of the crystal is undamaged. X-ray and Raman-scattering results prove that KTP films have good single-crystal properties. PMID- 26907436 TI - Germanium-on-silicon Vernier-effect photonic microcavities for the mid-infrared. AB - We present Vernier-effect photonic microcavities based on a germanium-on-silicon technology platform, operating around the mid-infrared wavelength of 3.8 MUm. Cascaded racetrack resonators have been designed to operate in the second regime of the Vernier effect, and typical Vernier comb-like spectra have been successfully demonstrated with insertion losses of ~5 dB, maximum extinction ratios of ~23 dB, and loaded quality factors higher than 5000. Furthermore, an add-drop racetrack resonator designed for a Vernier device has been characterized, exhibiting average insertion losses of 1 dB, extinction ratios of up to 18 dB, and a quality factor of ~1700. PMID- 26907437 TI - 3D micromanipulation at low numerical aperture with a single light beam: the focused-Bessel trap. AB - Full-three-dimensional (3D) manipulation of individual glass beads with radii in the range of 2-8 MUm is experimentally demonstrated by using a single Bessel light beam focused through a low-numerical-aperture lens (NA=0.40). Although we have a weight-assisted trap with the beam propagating upward, we obtain a stable equilibrium position well away from the walls of the sample cell, and we are able to move the particle across the entire cell in three dimensions. A theoretical analysis for the optical field and trapping forces along the lateral and axial directions is presented for the focused-Bessel trap. This trap offers advantages for 3D manipulation, such as an extended working distance, a large field of view, and reduced aberrations. PMID- 26907438 TI - Generation of coherent radiation in the vacuum ultraviolet using randomly quasi phase-matched strontium tetraborate. AB - Tunable coherent radiation is generated in the vacuum ultraviolet down to 121 nm using random quasi-phase matching in strontium tetraborate, the shortest wavelength ever produced with a second-order nonlinear optical process in a solid state material. Relevant properties of this radiation, the nonlinear process, and the nonlinear crystal are investigated. PMID- 26907440 TI - Fiber-optic radio frequency transfer based on passive phase noise compensation with frequency dividing and filtering. AB - In this Letter, a passive phase noise compensation-based fiber-optic frequency transfer scheme with frequency dividing and filtering is proposed. The probe signal is divided at the remote site and effectively discriminated from the backscattering noises by electrical bandpass filtering at the local site. By combining the bidirectional transmission with the same wavelength on a single fiber, the scheme can reach the maximum bidirectional propagation symmetry and effectively suppress the effect of backscattering at the same time. The proposed scheme is experimentally demonstrated and compared with the scheme with backscattering. The relative frequency stabilities of 3.9*10(-14)/s and 1.2*10( 16)/10(4) s are reached for 40 km transfer, which obviously outperform the scheme with backscattering, especially in terms of short-term stability, and are closed to the floor of the back-to-back experimental system. PMID- 26907439 TI - Experimental characterization of a 400 Gbit/s orbital angular momentum multiplexed free-space optical link over 120 m. AB - We experimentally demonstrate and characterize the performance of a 400-Gbit/s orbital angular momentum (OAM) multiplexed free-space optical link over 120 m on the roof of a building. Four OAM beams, each carrying a 100-Gbit/s quadrature phase-shift-keyed channel are multiplexed and transmitted. We investigate the influence of channel impairments on the received power, intermodal crosstalk among channels, and system power penalties. Without laser tracking and compensation systems, the measured received power and crosstalk among OAM channels fluctuate by 4.5 dB and 5 dB, respectively, over 180 s. For a beam displacement of 2 mm that corresponds to a pointing error less than 16.7 MUrad, the link bit error rates are below the forward error correction threshold of 3.8*10(-3) for all channels. Both experimental and simulation results show that power penalties increase rapidly when the displacement increases. PMID- 26907441 TI - High-efficiency near-infrared emission from Bismuth-doped SiO0.73 thin films fabricated by ion implantation technology. AB - Over the past decade, the possibility of near-infrared light generation and amplification on chip has attracted great interest for future monolithic integrated optical components. In this Letter, we demonstrated a CMOS-compatible method to fabricate amorphous SiO0.73 thin films doped with Bi ions. It exhibited highly improved sigma(em)*tau of up to 4.2*10(-23) cm2 s and greatly enhanced near-infrared characteristic emission originated from Bi ions by nearly 60 times via Si nanocrystal size control. We anticipated that this Bi-doped near-infrared light emitter would be a new starting point for future research in the field of optoelectronic integration. PMID- 26907442 TI - Tapered fluorotellurite microstructured fibers for broadband supercontinuum generation. AB - Fluorotellurite microstructured fibers (MFs) based on TeO2-BaF2-Y2O3 glasses are fabricated by using a rod-in-tube method. Tapered fluorotellurite MFs with varied transition region lengths are prepared by employing an elongation machine. By using a tapered fluorotellurite MF with a transition region length of ~3.3 cm as the nonlinear medium and a 1560 nm femtosecond fiber laser as the pump source, broadband supercontinuum generation covering from 470 to 2770 nm is obtained. The effects of the transition region length of the tapered fluorotellurite MF on supercontinuum generation are also investigated. Our results show that tapered fluorotellurite MFs are promising nonlinear media for generating broadband supercontinuum light expanding from visible to mid-infrared spectral region. PMID- 26907443 TI - Mode conversion in a tapered fiber via a whispering gallery mode resonator and its application as add/drop filter. AB - Based on the conversion between the fundamental mode (LP01) and the higher-order mode (LP11) in a tapered fiber via a whispering gallery mode resonator, an add/drop filter was proposed and demonstrated experimentally, in which the resonator only interacted with one tapered fiber, rather than two tapered fibers as in conventional configurations. The filter gains advantages of easy alignment and low scattering loss over the other filters based on tapered fiber and resonator, and will be useful in application. PMID- 26907444 TI - Three-dimensional vector recording in polarization sensitive liquid crystal composites by using axisymmetrically polarized beam. AB - Three-dimensional anisotropic structures were fabricated by a recording axisymmetrically polarized beam in azobenzene (azo)-dye doped liquid crystal polymer composites. Polarization and wavefront modulation properties of fabricated anisotropic structures are investigated by experimentally and theoretically analyzing the diffraction properties. Photo-induced anisotropic structures would be utilized to generate singular light waves, such as optical and polarization vortices. PMID- 26907445 TI - Tunable optical parametric generator based on the pump spatial walk-off. AB - We suggest a novel optical parametric generator (OPG) in which one of the downconverted beams is spontaneously generated along the Poynting vector of the pump beam. In this configuration, the generation takes advantage of the walk-off of the extraordinary pump, rather than being degraded by it. As a result, the generated signal and idler beams are bright due to a high conversion efficiency, spatially nearly single mode due to the preferred direction of the Poynting vector, tunable over a wide range of wavelengths and broadband. The two beams are also correlated in frequency and in the photon number per pulse. Furthermore, due to their thermal statistics, these beams can be used as a pump to efficiently generate other nonlinear processes. PMID- 26907446 TI - Laser-frequency locking to a whispering-gallery-mode cavity by spatial interference of scattered light. AB - We present a simple and effective method for frequency locking a laser source to a free-space-coupled whispering-gallery-mode cavity. The scheme relies on the interference of spatial modes contained in the light scattered by the cavity, where low- and high-order modes are simultaneously excited. A dispersion-shaped signal proportional to the imaginary component of the resonant optical field is simply generated by spatial filtering of the scattered light. Locking of a diode laser to the equatorial modes of a liquid droplet resonator is demonstrated using this scheme, and its performance is compared to the Pound-Drever-Hall technique. This new approach makes laser-frequency locking straightforward and shows a number of advantages, including robustness, low cost, and no need for sophisticated optical and electronic components. PMID- 26907447 TI - Generation of continuous variable quantum entanglement using a fiber optical parametric amplifier. AB - We demonstrate the experimental generation of quadrature amplitude entanglement in the 1550 nm band by using a fiber optical parametric amplifier. The measured noise variances of the difference and sum of the quadrature amplitudes of the pulsed signal and idler twin beams fall below the shot noise limit by about 1 and 0.8 dB (4.2 and 3.6 dB after the correction for efficiency), respectively, showing that the inseparability criterion of Einstein-Podolsky-Rosen entanglement I<2 is satisfied. Our investigation reveals that the quality of the measured entanglement can be further improved by increasing the transmission efficiency of the twin beams and by optimizing the temporal mode matching of the two sets of homodyne detection systems. PMID- 26907448 TI - Clinical Trial Accrual Targeting Genomic Alterations After Next-Generation Sequencing at a Non-National Cancer Institute-Designated Cancer Program. AB - PURPOSE: Successful clinical trial accrual targeting uncommon genomic alterations will require broad national participation from both National Cancer Institute (NCI)-designated comprehensive cancer centers and community cancer programs. This report describes the initial experience with clinical trial accrual after next generation sequencing (NGS) from three affiliated non-NCI-designated cancer programs. MATERIALS AND METHODS: Clinical trial participation was reviewed after enrollment of the first 200 patients undergoing comprehensive genomic profiling by NGS as part of an institutional intuitional review board-approved protocol at three affiliated hospitals in Rhode Island and was compared with published experience from NCI-designated cancer centers. RESULTS: Patient characteristics included a median age of 64 years, a median of two lines of prior therapy, and a predominance of GI carcinomas (58%). One hundred sixty-four of 200 patients (82%) had adequate tumor for NGS, 95% had genomic alterations identified, and 100% had variants of unknown significance. Fifteen of 164 patients (9.2%) enrolled in genotype-directed clinical trials, and three patients (1.8%) received commercially available targeted agents off clinical trials. The reasons for nonreceipt of NGS-directed therapy were no locally available matching trial (48.6%), ineligibility (33.6%) because of comorbidities or interim clinical deterioration, physician's choice of a different therapy (6.8%), or stable disease (11%). CONCLUSION: This experience demonstrates that a program enrolling patients in specific targeted agent clinical trials after NGS can be implemented successfully outside of the NCI-designated cancer program network, with comparable accrual rates. This is important because targetable genes have rare mutation rates and clinical trial accrual after NGS is low. PMID- 26907449 TI - Analysis of After-Hours Patient Telephone Calls in Two Academic Radiation Oncology Departments: An Opportunity for Improvement in Patient Safety and Quality of Care. AB - PURPOSE: Patient care within radiation oncology extends beyond the clinic or treatment hours. The on-call radiation oncologist is often not a patient's primary radiation oncologist, introducing the possibility of communication breakdowns and medical errors. This study analyzed after-hours telephone calls to identify opportunities for improved patient safety and quality of care. METHODS AND MATERIALS: Patient calls received outside of business hours between July 1, 2013, and June 30, 2014, at two academic radiation oncology departments were retrospectively reviewed. All calls were analyzed using content analysis, and descriptive analyses were performed. RESULTS: During this time, 5,557 courses of radiotherapy (RT) were delivered. A total of 454 calls were received from 369 unique patients (81%), averaging 4.4 calls per week per department. Phone encounters were documented for 223 calls (49%). The calls were categorized by disease site (No., %): central nervous system (91, 20%), head and neck (78, 17%), genitourinary (53, 12%), GI (52, 12%), thoracic (51, 11%), gynecologic (30, 7%), breast (24, 5%), and other (75, 17%). Patients most often called regarding acute medical, non-RT-related issues (144 calls, 32%); acute RT-related adverse effects (127, 28%); and medication management, including refills (63, 14%). CONCLUSION: This analysis provided novel information regarding the volume of and reasons for after-hours patient-initiated telephone calls. It identified opportunities for actionable improvements in safety and quality of care, particularly with regard to documentation by on-call providers, communication with the primary radiation oncology and extended health care teams, patient education about common RT adverse effects, and medication management. PMID- 26907450 TI - Insurance Denial of Coverage for Patients Enrolled in Cancer Clinical Trials Is Still a Problem in the Affordable Care Act Era. PMID- 26907451 TI - Identification of Key Gaps in Cancer Survivorship Research: Findings From the American Society of Clinical Oncology Survey. PMID- 26907452 TI - Economic Implications of Widespread Expansion of Frozen Section Margin Analysis to Guide Surgical Resection in Women With Breast Cancer Undergoing Breast Conserving Surgery. AB - PURPOSE: In the current health care environment, cost effectiveness is critically important in policy setting and care of patients. This study performed a health economic analysis to assess the implications to providers and payers of expanding the use of frozen section margin analysis to minimize reoperations for patients undergoing breast cancer lumpectomy. METHODS: A health care economic impact model was built to assess annual costs associated with breast lumpectomy procedures with and without frozen section margin analysis to avoid reoperation. RESULTS: If frozen section margin analysis is used in 20% of breast lumpectomies and under a baseline assumption that 35% of initial lumpectomies without frozen section analysis result in reoperations, the potential annual cost savings are $18.2 million to payers and $0.4 million to providers. Under the same baseline assumption, if 100% of all health care facilities adopted the use of frozen section margin analysis for breast lumpectomy procedures, the potential annual cost savings are $90.9 million to payers and $1.8 million to providers. On the basis of 10,000 simulations, use of intraoperative frozen section margin analysis yields cost saving for payers and is cost neutral to slightly cost saving for providers. CONCLUSION: This economic analysis indicates that widespread use of frozen section margin evaluation intraoperatively to guide surgical resection in breast lumpectomy cases and minimize reoperations would be beneficial to cost savings not only for the patient but also for payers and, in most cases, for providers. PMID- 26907454 TI - The role of inhibitory control in the hospitalization of children with severe psychiatric disorders. PMID- 26907453 TI - Identifying Severe Adverse Event Clusters Using the National Cancer Institute's Common Terminology Criteria for Adverse Events. AB - PURPOSE: Exploring the relationships among adverse events is important because those that arise from a common mechanism are amenable to a common intervention, which can improve symptom management, quality of life, and treatment adherence. To date, symptom cluster studies have used patient-reported data, which are not always available in clinical trials. In this study, we proposed using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) to identify adverse event clusters because the CTCAE data are collected as standard practice and can therefore be used when patient-reported outcomes are unavailable. METHODS: The CTCAE data from a randomized clinical trial conducted by SWOG that compared docetaxel plus estramustine versus mitoxantrone plus predinsone in patients with advanced prostate cancer were used to identify severe adverse event clusters. A variable based hierarchical cluster analysis was conducted using the CTCAE for the 323 patients who experienced at least one grade 3 or higher adverse event. RESULTS: A total of 109 adverse event types were captured using the CTCAE. Four clusters had moderate associations: nausea, vomiting, and anorexia (n = 35, r = 0.45); joint/bone(myalgia, arthralgia, and arthritis) and muscle weakness (n = 26, r = 0.29); anemia and transfusion (n = 20, r = 0.38); and neutrophils/granulocytes, febrile neutropenia, and leukocytes/lymphopenia (n = 114, r = 0.29). Two clusters had weak associations: fatigue/malaise/lethargy and dehydration (n = 66, r = 0.12); and constipation, infection without neutropenia, and abdominal pain/cramping (n = 35, r = 0.13). CONCLUSION: Several severe adverse event clusters were identified in patients with advanced prostate cancer. Identifying adverse event clusters using CTCAE data from clinical trials is feasible. PMID- 26907455 TI - Thermal analysis of polyethylene + X% carbon nanotubes. AB - The aim of this research is to study the influence of the multi-walled carbon nanotubes (MWCNTs) on the thermomechanical and structural properties of high density polyethylene. Several, complementary experimental techniques were used, namely, dilatometry, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Raman spectroscopy, and infrared (IR) spectroscopy. Dilatometry data showed that nanocomposites exhibit anisotropic behavior, and intensity of the anisotropy depends on the MWCNT concentration. The shapes of the dilatometric curves of the nanocomposites under study differ significantly for the radial and longitudinal directions of the samples. DSC results show that MWCNTs weekly influence calorimetry data, while Raman spectra show that the I D/I G ratio decreases when MWCNT concentration increases. The IR spectra demonstrate improvement of the crystallinity of the samples as the content in MWCNTs rises. PMID- 26907456 TI - The painDETECT project - far more than a screening tool on neuropathic pain. AB - Background and objectives The painDETECT questionnaire (PD-Q), a simple and reliable screening questionnaire of neuropathic pain, was developed in 2004 in cooperation with the German Research Network on Neuropathic Pain. The initial aim was to implement quality management and to improve the situation of neuropathic pain (NeP) patients in Germany. The PD-Q proved immediately successful and was translated into and validated in multiple languages. Subsequently a comprehensive electronic system (PD) comprising various validated questionnaires with regard to pain typical comorbidities, such as function, sleep, mood or anxiety, was implemented Germany wide. We aimed to provide a comprehensive overview about the development and validation as well as the application of the PD-Q in various clinical conditions. Methods This overview is based on a literature search on English full-text papers using the term 'painDETECT' in Medline and PubMed covering the time period from 2006 to September 2015, amended with further publications cited in the retrieved publications or provided by the questionnaire developers. Results PD-Q as screening tool for NeP described in patients with lower back pain (8 studies), rheumatoid arthritis and osteoarthritis (10), thoracotomy (2 studies), tumor diseases (4 studies), fibromyalgia (4 studies), diverse musculoskeletal conditions (12 studies) and diverse other conditions (10 studies). In addition, the PD-Q was used in 9 studies that investigated the effect of drugs for the treatment of patients with a NeP component. Conclusion To date more than 300,000 patients were assessed, providing the basis for one of the world's largest datasets for chronic pain. Among others the extensive pool of PD Q data triggered the idea of subgrouping patients on the basis of their individual sensory profiles which might in the future lead to a stratified treatment approach and ultimately to personalized therapy. Started as a healthcare utilization project in Germany, the PD-Q is nowadays used for clinical and research purposes around the world. PMID- 26907457 TI - Chemical Mechanism of the Phosphotriesterase from Sphingobium sp. Strain TCM1, an Enzyme Capable of Hydrolyzing Organophosphate Flame Retardants. AB - The mechanism of action of the manganese-dependent phosphotriesterase from Sphingobium sp. strain TCM1 that is capable of hydrolyzing organophosphate flame retardants was determined. The enzyme was shown to hydrolyze the RP-enantiomer of O-methyl O-cyclohexyl p-nitrophenyl thiophosphate with net inversion of configuration and without the formation of a covalent reaction intermediate. These results demonstrate that the enzyme catalyzes the hydrolysis of substrates by activation of a nucleophilic water molecule for direct attack at the phosphorus center. PMID- 26907458 TI - Wrinkling Measurement of the Mechanical Properties of Drying Salt Thin Films. AB - We report a time-resolved approach to probe the mechanical properties of thin films during drying and solidification based on surface wrinkling. The approach is demonstrated by measuring the modulus of a ternary system comprising an inorganic salt (aluminum chlorohydrate), a humectant (glycerol), and water across the glassy film formation pathway. The topography of mechanically induced wrinkling of supported films on polydimethylsiloxane (PDMS) is experimentally monitored during mechanical extension and relaxation cycles. Nontrivial aspects of our method include the need to oxidize the (hydrophobic) PDMS surface prior to solution deposition to enable surface wetting, which simultaneously creates a glassy-layer skin, whose wrinkling can contribute to the overall topography. Film drying is studied as a function of solution concentration and time, and a range of pattern morphologies are found: sinusoidal wrinkling, transient double wavelength wrinkling accompanying film "crust" formation, ridging associated with stress localization, and cracking. We quantify the evolution of the elastic modulus during the sinusoidal wrinkling stage, employing bi- and trilayer models, which are independently confirmed by nanoindentation. The method provides thus a simple and robust approach for the mechanical characterization of out-of equilibrium thin films. PMID- 26907459 TI - The impact of psychosocial stressors on postpartum weight retention. AB - Excessive gestational weight gain and postpartum weight retention are implicated in future morbidity in women. To understand whether psychosocial stressors contribute to weight retention, we used data collected in a cohort of postpartum women and analyzed measures of stress, depression, social support, and health related quality of life. Depressive symptoms at delivery and worse health-related quality of life and lower stress at 3 months postpartum were associated with 3 month weight retention. Interventions targeting depression and improving quality of life may further reduce weight retained. PMID- 26907460 TI - The right location? Experiences of refugee adolescents seen by school-based mental health services. AB - Access to needed mental health services can be particularly difficult for newly arrived refugee and asylum-seeking adolescents, although many attend school. This study examined young refugees' impressions and experience of mental health services integrated within the school system. Semi-structured interviews were conducted with 40 adolescent refugees discharged by three school-based mental health services across the United Kingdom. Two-thirds preferred to be seen at school. Rumination and worry about insecurity in the asylum process had a negative impact particularly on the adolescents' social functioning and ability to focus at school. The important role played by teachers in supporting and mediating contact with mental health services was valued by those interviewed. The study confirms that schools offer an important location for mental health services for adolescent refugees and provide an important portal for integration of services. PMID- 26907461 TI - Skeletal metastases and impact of anticancer and bone-targeted agents in patients with castration-resistant prostate cancer. AB - Incidence of bone metastases is very high in advanced prostate cancer patients. Bone metastases likely have a significant impact on functional status and quality of life, not only related to pain, but also to the relevant risk of skeletal related events. A better understanding of mechanisms associated with bone metastatic disease secondary to prostate cancer and more specifically to the cross-talk between tumor cells and bone microenvironment in metastatic progression represented the background for the development of new effective bone targeted therapies. Furthermore, a better knowledge of biological mechanisms driving disease progression led to significant advances in the treatment of castration-resistant prostate cancer, with the development and approval of new effective drugs. Aim of this review is to outline the physiopathology of bone metastases in prostate cancer and summarize the main results of clinical trials conducted with different drugs to control morbidity induced by skeletal metastases and bone disease progression. For each agent, therapeutic effect on bone metastases has been measured in terms of pain control and/or incidence of skeletal-related events, usually defined as a composite endpoint, including the need for local treatment (radiation therapy or surgery), spinal cord compression, pathological bone fractures. In details, data obtained with chemotherapy (mitoxantrone, docetaxel, cabazitaxel), new generation hormonal agents (abiraterone, enzalutamide), radium-223, bone-targeted agents (zoledronic acid, denosumab) and with several experimental agents (cabozantinib, dasatinib, anti endothelin and other agents) in patients with castration-resistant prostate cancer are reviewed. PMID- 26907463 TI - A Bronsted Acid-Amino Acid as a Synergistic Catalyst for Asymmetric List-Lerner Barbas Aldol Reactions. AB - Herein, for the first time, a combination of L-amino acid, (R)-5,5-dimethyl thiazolidinium-4-carboxylate (L-DMTC) with simple Bronsted acid TFA is reported as the suitable synergistic catalyst for the List-Lerner-Barbas aldol (LLB-A) reaction of less reactive 2-azidobenzaldehydes with various ketones at ambient temperature to furnish the optically active functionalized (2 azidophenyl)alcohols with very good yields, dr's, and ee's. This method gives first time access to the novel azido-containing multifunctional compounds, which are applicable in material to medicinal chemistry. Chiral functionalized (2 azidophenyl)alcohols were transformed into different molecular scaffolds in good yields with high selectivity through Lewis acid mediated NaBH4 reduction, aza Wittig and Staudinger reaction (azide reduction), followed by oxidative cyclizations, allenone synthesis, and click reaction, respectively. Chiral LLB-A products might become suitable starting materials for the total synthesis of natural products, ingredients, and inhibitors in medicinal chemistry. The mechanistic synergy of L-DMTC with TFA to increase the rate and selectivity of LLB-A reaction in DMSO-D6 is explained with the controlled and online NMR experiments. PMID- 26907462 TI - Thirty-day rat toxicity study reveals reversible liver toxicity of mifepristone (RU486) and metapristone. AB - OBJECTIVE: Mifepristone (RU486) is an oral first-line contraceptive used by hundreds of millions of women, and recently it was tested for anticancer activity in both genders worldwide. We are developing metapristone (the N-monodemethyl RU486) as a potential metastasis chemopreventive. The present acute and 30-d subacute toxicity study aimed at examining and compared in parallel the potential toxicity of the two drugs. METHODS: The single-dose acute toxicity and 30-d subacute toxicity studies were conducted in mice and rats, respectively, by gavaging metapristone or mifepristone at various doses. Blood samples and organs were collected for blood chemistry, hematology and histology analyses. RESULTS: Oral mifepristone (3000 mg/kg) caused 30% and 40% death in female and male mice, respectively, within 15 h post-dosing. In comparison, the same dose of metapristone produced 30% acute death in males only. Thirty-day oral administration of the two drugs to rats (12.5, 50 and 200 mg/kg/day) caused reversible hepatotoxicity that only occurred at 200 mg/kg/day group, evidenced by the elevated liver enzyme activity and liver organ weight. CONCLUSION: The present study, for the first time, reveals reversible hepatotoxicity in rats caused by the 30-d consecutive administration at the high dose, and warns the potential hepatotoxicity caused by long-term administrations of high doses of mifepristone or metapristone in clinical trials but not by the acute single abortion doses. PMID- 26907464 TI - Total sitting time and the risk of incident diabetes in Danish adults (the DANHES cohort) over 5 years: a prospective study. AB - AIMS: To test the hypothesis that total sitting time is associated with incident diabetes, after adjustment for physical activity and obesity. METHODS: 72 608 Danish adults from the DANHES cohort reported their total sitting time in 2007 2008 and were followed-up for 5 years, in relation to register-based incident diabetes mellitus. Cox regression analyses were used, and the effect-modifying influence of obesity and physical activity assessed. RESULTS: The age-sex adjusted HR for developing diabetes among those who sat 10+ h/day as compared to <6 h/day was 1.35 (95% CI 1.17 to 1.57). The relative risks were similar by gender, but were largely attenuated by adjustment for potential confounding factors including physical activity, and statistically non-significant for all categories of body mass index except the obese. CONCLUSIONS: The association between total sitting time and incident diabetes is substantially moderated by physical activity and obesity. Total sitting time remains a risk factor for diabetes only in inactive and obese populations. PMID- 26907465 TI - The management of symptomatic femoroacetabular impingement: what is the rationale for non-surgical treatment? PMID- 26907467 TI - Novel Y-chromosomal microdeletions associated with non-obstructive azoospermia uncovered by high throughput sequencing of sequence-tagged sites (STSs). AB - Y-chromosomal microdeletion (YCM) serves as an important genetic factor in non obstructive azoospermia (NOA). Multiplex polymerase chain reaction (PCR) is routinely used to detect YCMs by tracing sequence-tagged sites (STSs) in the Y chromosome. Here we introduce a novel methodology in which we sequence 1,787 (post-filtering) STSs distributed across the entire male-specific Y chromosome (MSY) in parallel to uncover known and novel YCMs. We validated this approach with 766 Chinese men with NOA and 683 ethnically matched healthy individuals and detected 481 and 98 STSs that were deleted in the NOA and control group, representing a substantial portion of novel YCMs which significantly influenced the functions of spermatogenic genes. The NOA patients tended to carry more and rarer deletions that were enriched in nearby intragenic regions. Haplogroup O2* was revealed to be a protective lineage for NOA, in which the enrichment of b1/b3 deletion in haplogroup C was also observed. In summary, our work provides a new high-resolution portrait of deletions in the Y chromosome. PMID- 26907468 TI - Erratum to: Identification of novel CSF biomarkers for neurodegeneration and their validation by a high-throughput multiplexed targeted proteomic assay. PMID- 26907466 TI - Metal-dependent Deacetylases: Cancer and Epigenetic Regulators. AB - Epigenetic regulation is a key factor in cellular homeostasis. Post-translational modifications (PTMs) are a central focus of this regulation as they function as signaling markers within the cell. Lysine acetylation is a dynamic, reversible PTM that has garnered recent attention due to alterations in various types of cancer. Acetylation levels are regulated by two opposing enzyme families: lysine acetyltransferases (KATs) and histone deacetylases (HDACs). HDACs are key players in epigenetic regulation and have a role in the silencing of tumor suppressor genes. The dynamic equilibrium of acetylation makes HDACs attractive targets for drug therapy. However, substrate selectivity and biological function of HDAC isozymes is poorly understood. This review outlines the current understanding of the roles and specific epigenetic interactions of the metal-dependent HDACs in addition to their roles in cancer. PMID- 26907469 TI - Commissioning services and Primary Health Networks. AB - Commissioning is set to become a stronger feature in the Australian health system as Primary Health Networks embrace it as a tool for improving population health outcomes. International experience shows that developing into a commissioning organisation is not always easy. Drawing on international experiences of commissioning, as well as those from the Australian hospital sector, will help smooth the path for Primary Health Networks. PMID- 26907470 TI - Supramolecular assemblies of histidinylated beta-cyclodextrin for enhanced oligopeptide delivery into osteoclast precursors. AB - Much attention has been given to the problem of drug delivery through the cell membrane in order to treat and manage bone diseases recently. The aim of this study was to develop nanoparticles made of amino- and histidinyl-modified amphiphilic beta-cyclodextrins (beta-CDs) entrapping osteoclast inhibitor, a hydrophobic oligopeptides drug, across the membrane of bone marrow-derived macrophages (BMMs). Drug-loaded beta-CDs nanoparticles (NPs) were prepared by the emulsion solvent evaporation technique and fully characterized for size, zeta potential, and entrapment efficiency. Spherical NPs displaying a hydrodynamic radius of about 295 nm which did not change upon storage as an aqueous dispersion, a positive zeta potential, and entrapment efficiency of drug very close to 98% were produced. Flow cytometry and spectrofluorimetry analysis indicated that the model drug itself was not taken up by the BMMs; however, NP systems underwent significant cellular uptake. In particular, histidinyl group modified CD (beta-CD-H) NPs were taken up more efficiently than amino group modified (beta-CD-A) ones. Cellular uptake mechanism study demonstrated that the permeability of drug-loaded NPs across the membrane of BMMs is probably due to macropinocytosis pathway. Cell viability studies showed that both beta-CD-A and beta-CD-H exhibited no significant cytotoxicity up to 1.0 mg/ml against the cells. These results highlight the developed beta-CD-H NPs have great potential in safely and effectively delivering osteoclast inhibitors and other therapeutic agents toward bone disease. PMID- 26907471 TI - From here to epilepsy: the risk of seizure in patients with Alzheimer's disease. AB - To describe the association between Alzheimer's disease and seizures by reviewing epidemiological data from available literature and to assess the putative pathophysiological links between neurodegeneration and altered cortical excitability. We also discuss specific antiepileptic treatment strategies in patients with Alzheimer's disease, as well as transient epileptic amnesia as a possible crossroads between degeneration and epilepsy. Regarding epidemiology, we searched publications in Pubmed, Medline, Scopus and Web of Science (until September 2015) using the keywords "incidence", "prevalence" and "frequency", as well as "Alzheimer's disease" and "seizures". In addition, therapeutic aspects for seizures in Alzheimer's disease were searched using the key words "antiepileptic drugs", "seizure treatment" and "Alzheimer". The prevalence and incidence rates of seizures were found to be increased 2 to 6-fold in patients with Alzheimer's disease compared to age-adjusted control patients. Treatment strategies have mainly been extrapolated from elderly patients without dementia, except for one single randomised trial, in which levetiracetam, lamotrigine and phenobarbital efficacy and tolerance were investigated in patients with Alzheimer's disease. Mouse models appear to show a major role of amyloid precursor protein and its cleavage products in the generation of cortical hyperexcitability. A link between Alzheimer's disease and epilepsy has long been described and recent cohort studies have more clearly delineated risk factors associated with the genesis of seizures, such as early onset and possibly severity of dementia. As genetic forms of Alzheimer's disease and experimental mouse models suggest, beta-amyloid may play a prominent role in the propagation of synchronised abnormal discharges, perhaps more via an excitatory mode than a direct neurodegenerative effect. PMID- 26907472 TI - In Reply: Preoperative Mapping in Unicompartmental Knee Arthroplasty Using Computed Tomography Scans Is Associated With Radiation Exposure and Carries High Cost. PMID- 26907474 TI - The atmospheric oxidation of dimethyl, diethyl, and diisopropyl ethers. The role of the intramolecular hydrogen shift in peroxy radicals. AB - The atmospheric oxidation mechanisms of dimethyl ether (DME), diethyl ether (DEE) and diisopropyl ether (DiPE) are studied by using quantum chemistry and unimolecular reaction theory (RRKM-ME) calculations. For the peroxy radical CH3OCH2O2 from DME, a barrier height of ~ 85 kJ mol(-1) is found for its intramolecular H-shift to CH2OCH2OOH, which can recombine rapidly with the atmospheric O2. RRKM-ME calculations obtain an effective rate of ~ 0.1 s(-1) at 298 K for the formation of O2CH2OCH2OOH. For similar radicals in DEE and DiPE, effective rates are 1.6 s(-1) and 1.1 s(-1), respectively. In the atmosphere, these unimolecular reactions are fast enough to compete with the bimolecular reactions with NO and/or HO2, especially when [NO] is low. The fates of radicals after the H-shifts are also examined here. Several subsequent reactions are found to recycle OH radicals. New mechanisms are proposed on the basis of present calculations and are consistent with previous experimental results. In the atmosphere, the routes via H-shifts represent an auto-oxidation of these ethers with no involvement of NOx and therefore no O3 formation, and also a self cleaning mechanism of organic compounds due to recycling of OH radicals. Some of the end products are highly oxidized with multifunctional groups and high O : C ratios, suggesting their low volatility and potential contribution to secondary organic aerosols. PMID- 26907475 TI - Biotransformation of synthetic cannabinoids JWH-018, JWH-073 and AM2201 by Cunninghamella elegans. AB - Being marketed as "legal" smoking blends or mixtures, synthetic cannabinoids are abused widely owing to its cannabis-like effect. Due to the rapid introduction of new generation analogues of synthetic cannabinoids to escape from legislative/judicial control, the investigation of the metabolic pathways of these substances is of particular importance for drug control, abstinence and forensic toxicology purposes. In this study, the in vitro metabolism of JWH-018, JWH-073 and AM2201 by the fungus Cunninghamella elagans has been investigated with the purpose of validating its potential as a complementary model for investigating synthetic cannabinoid metabolism. JWH-018, JWH-073 and AM2201 were incubated for 72h with C. elegans. Detection of metabolites was based on liquid chromatography-tandem mass spectrometry and high resolution mass spectrometry analysis. C. elegans was found capable of producing the majority of the phase I metabolites observed in earlier in vitro and in vivo mammalian studies as a result of monohydroxylation, dihydroxylation, carboxylation, dehydrogenation, ketone formation, dihydrodiol formation, dihydrodiol formation with N dealkylation and combinations thereof. C. elegans can thus be a useful and economic model for studying synthetic cannabinoid metabolism. PMID- 26907473 TI - Differential regulation of TRPV1 channels by H2O2: implications for diabetic microvascular dysfunction. AB - We demonstrated previously that TRPV1-dependent coupling of coronary blood flow (CBF) to metabolism is disrupted in diabetes. A critical amount of H2O2 contributes to CBF regulation; however, excessive H2O2 impairs responses. We sought to determine the extent to which differential regulation of TRPV1 by H2O2 modulates CBF and vascular reactivity in diabetes. We used contrast echocardiography to study TRPV1 knockout (V1KO), db/db diabetic, and wild type C57BKS/J (WT) mice. H2O2 dose-dependently increased CBF in WT mice, a response blocked by the TRPV1 antagonist SB366791. H2O2-induced vasodilation was significantly inhibited in db/db and V1KO mice. H2O2 caused robust SB366791 sensitive dilation in WT coronary microvessels; however, this response was attenuated in vessels from db/db and V1KO mice, suggesting H2O2-induced vasodilation occurs, in part, via TRPV1. Acute H2O2 exposure potentiated capsaicin-induced CBF responses and capsaicin-mediated vasodilation in WT mice, whereas prolonged luminal H2O2 exposure blunted capsaicin-induced vasodilation. Electrophysiology studies re-confirms acute H2O2 exposure activated TRPV1 in HEK293A and bovine aortic endothelial cells while establishing that H2O2 potentiate capsaicin-activated TRPV1 currents, whereas prolonged H2O2 exposure attenuated TRPV1 currents. Verification of H2O2-mediated activation of intrinsic TRPV1 specific currents were found in isolated mouse coronary endothelial cells from WT mice and decreased in endothelial cells from V1KO mice. These data suggest prolonged H2O2 exposure impairs TRPV1-dependent coronary vascular signaling. This may contribute to microvascular dysfunction and tissue perfusion deficits characteristic of diabetes. PMID- 26907478 TI - Modelling and Bayesian adaptive prediction of individual patients' tumour volume change during radiotherapy. AB - The aim of this study is to develop a mathematical modelling method that can predict individual patients' response to radiotherapy, in terms of tumour volume change during the treatment. The main concept is to start from a population average model, which is subsequently updated from an individual's tumour volume measurement. The model becomes increasingly personalized and so too does the prediction it produces. This idea of adaptive prediction was realised by using a Bayesian approach for updating the model parameters. The feasibility of the developed method was demonstrated on the data from 25 non-small cell lung cancer patients treated with helical tomotherapy, during which tumour volume was measured from daily imaging as part of the image-guided radiotherapy. The method could provide useful information for adaptive treatment planning and dose scheduling based on the patient's personalised response. PMID- 26907476 TI - Opposing roles of LTB4 and PGE2 in regulating the inflammasome-dependent scorpion venom-induced mortality. AB - Tityus serrulatus sting causes thousands of deaths annually worldwide. T. serrulatus-envenomed victims exhibit local or systemic reaction that culminates in pulmonary oedema, potentially leading to death. However, the molecular mechanisms underlying T. serrulatus venom (TsV) activity remain unknown. Here we show that TsV triggers NLRP3 inflammasome activation via K(+) efflux. Mechanistically, TsV triggers lung-resident cells to release PGE2, which induces IL-1beta production via E prostanoid receptor 2/4-cAMP-PKA-NFkappaB-dependent mechanisms. IL-1beta/IL-1R actions account for oedema and neutrophil recruitment to the lungs, leading to TsV-induced mortality. Inflammasome activation triggers LTB4 production and further PGE2 via IL-1beta/IL-1R signalling. Activation of LTB4-BLT1/2 pathway decreases cAMP generation, controlling TsV-induced inflammation. Exogenous administration confirms LTB4 anti-inflammatory activity and abrogates TsV-induced mortality. These results suggest that the balance between LTB4 and PGE2 determines the amount of IL-1beta inflammasome-dependent release and the outcome of envenomation. We suggest COX1/2 inhibition as an effective therapeutic intervention for scorpion envenomation. PMID- 26907477 TI - IkappaBalpha mediates prostate cancer cell death induced by combinatorial targeting of the androgen receptor. AB - BACKGROUND: Combining different clinical agents to target multiple pathways in prostate cancer cells, including androgen receptor (AR) signaling, is potentially an effective strategy to improve outcomes for men with metastatic disease. We have previously demonstrated that sub-effective concentrations of an AR antagonist, bicalutamide, and the histone deacetylase inhibitor, vorinostat, act synergistically when combined to cause death of AR-dependent prostate cancer cells. METHODS: In this study, expression profiling of human prostate cancer cells treated with bicalutamide or vorinostat, alone or in combination, was employed to determine the molecular mechanisms underlying this synergistic action. Cell viability assays and quantitative real time PCR were used to validate identified candidate genes. RESULTS: A substantial proportion of the genes modulated by the combination of bicalutamide and vorinostat were androgen regulated. Independent pathway analysis identified further pathways and genes, most notably NFKBIA (encoding IkappaBalpha, an inhibitor of NF-kappaB and p53 signaling), as targets of this combinatorial treatment. Depletion of IkappaBalpha by siRNA knockdown enhanced apoptosis of prostate cancer cells, while ectopic overexpression of IkappaBalpha markedly suppressed cell death induced by the combination of bicalutamide and vorinostat. CONCLUSION: These findings implicate IkappaBalpha as a key mediator of the apoptotic action of this combinatorial AR targeting strategy and a promising new therapeutic target for prostate cancer. PMID- 26907479 TI - Pushing the Limits: The Pattern and Dynamics of Rubber Monoculture Expansion in Xishuangbanna, SW China. AB - The rapidly growing car industry in China has led to an equally rapid expansion of monoculture rubber in many regions of South East Asia. Xishuangbanna, the second largest rubber planting area in China, located in the Indo-Burma biodiversity hotspot, supplies about 37% of the domestic natural rubber production. There, high income possibilities from rubber drive a dramatic expansion of monoculture plantations which poses a threat to natural forests. For the first time we mapped rubber plantations in and outside protected areas and their net present value for the years 1988, 2002 (Landsat, 30 m resolution) and 2010 (RapidEye, 5 m resolution). The purpose of our study was to better understand the pattern and dynamics of the expansion of rubber plantations in Xishuangbanna, as well as its economic prospects and conservation impacts. We found that 1) the area of rubber plantations was 4.5% of the total area of Xishuangbanna in 1988, 9.9% in 2002, and 22.2% in 2010; 2) rubber monoculture expanded to higher elevations and onto steeper slopes between 1988 and 2010; 3) the proportion of rubber plantations with medium economic potential dropped from 57% between 1988 and 2002 to 47% in 2010, while the proportion of plantations with lower economic potential had increased from 30% to 40%; and 4) nearly 10% of the total area of nature reserves within Xishuangbanna has been converted to rubber monoculture by 2010. On the basis of our findings, we conclude that the rapid expansion of rubber plantations into higher elevations, steeper terrain, and into nature reserves (where most of the remaining forests of Xishuangbanna are located) poses a serious threat to biodiversity and environmental services while not producing the expected economic returns. Therefore, it is essential that local governments develop long-term land use strategies for balancing economic benefits with environmental sustainability, as well as for assisting farmers with the selection of land suitable for rubber production. PMID- 26907481 TI - [Golimumab Therapy in Ulcerative Colitis]. AB - Ulcerative colitis is a chronic inflammatory condition of the colon, characterized by diffuse mucosal inflammation and blood-mixed diarrhea. The main treatment has been 5-aminosalicylic acid, steroid, thiopurine, and anti-tumor necrosis factor alpha (TNF-alpha) antibodies including infliximab, adalimumab, and golimumab. Golimumab, a new anti-TNF-alpha agent has been recently approved for patients with moderate to severe ulcerative colitis. Its efficacy and safety has been demonstrated in line with infliximab and adalimumab in preclinical and clinical studies. This review will focus on golimumab therapy in ulcerative colitis. PMID- 26907480 TI - How social interactions affect emotional memory accuracy: Evidence from collaborative retrieval and social contagion paradigms. AB - In daily life, emotional events are often discussed with others. The influence of these social interactions on the veracity of emotional memories has rarely been investigated. The authors (Choi, Kensinger, & Rajaram Memory and Cognition, 41, 403-415, 2013) previously demonstrated that when the categorical relatedness of information is controlled, emotional items are more accurately remembered than neutral items. The present study examined whether emotion would continue to improve the accuracy of memory when individuals discussed the emotional and neutral events with others. Two different paradigms involving social influences were used to investigate this question and compare evidence. In both paradigms, participants studied stimuli that were grouped into conceptual categories of positive (e.g., celebration), negative (e.g., funeral), or neutral (e.g., astronomy) valence. After a 48-hour delay, recognition memory was tested for studied items and categorically related lures. In the first paradigm, recognition accuracy was compared when memory was tested individually or in a collaborative triad. In the second paradigm, recognition accuracy was compared when a prior retrieval session had occurred individually or with a confederate who supplied categorically related lures. In both of these paradigms, emotional stimuli were remembered more accurately than were neutral stimuli, and this pattern was preserved when social interaction occurred. In fact, in the first paradigm, there was a trend for collaboration to increase the beneficial effect of emotion on memory accuracy, and in the second paradigm, emotional lures were significantly less susceptible to the "social contagion" effect. Together, these results demonstrate that emotional memories can be more accurate than nonemotional ones even when events are discussed with others (Experiment 1) and even when that discussion introduces misinformation (Experiment 2). PMID- 26907482 TI - [Comparison on Oral versus Intravenous Proton Pump Inhibitors for Prevention of Bleeding after Endoscopic Submucosal Dissection of Gastric Lesions]. AB - BACKGROUND/AIMS: Although intravenous proton pump inhibitor (PPI) has been used for the prevention of post endoscopic submucosal dissection (ESD) bleeding, the route of administration has not been confirmed. The aim of the present study was to compare the efficacy of intravenous and oral PPI administration for the prevention of delayed post ESD bleeding. METHODS: Total 166 consecutive patients were randomly assigned to 30 mg lansoprazol twice a day (PO group) and 120 mg pantoprazole intravenous injection (IV group) for 48 hours. Finally, 65 patients in PO group and 87 patients in IV group were analyzed. After ESD, all patients underwent follow up endoscopy after 24 hours and were observed the symptoms of bleeding up to 60 days after ESD. RESULTS: Age, sex and use of anticoagulants were not different between groups. At follow up endoscopy after 24 hours, oozing and exposed vessel was noted in 4.6% of PO group and 8.0% of IV group and there was no significant difference. Delayed bleeding occurred in 4 of 65 patients (6.2%) in the PO group and 8 of 87 patients (9.2%) in the IV group (p>0.999). By multivariate analysis, oozing or exposed vessels at follow up endoscopy were risk factors for delayed bleeding (OR=17.5, p=0.022). CONCLUSIONS: There was no significant difference in the delayed bleeding, length of hospital stay according to the administration route. Bleeding stigmata at follow up endoscopy was risk factor of delayed bleeding. Oral PPI administration can cost-effectively replace IV PPI for prevention of post ESD bleeding. PMID- 26907483 TI - Clinical Outcomes in Hospitalized Patients with Clostridium difficile Infection by Age Group. AB - BACKGROUND/AIMS: Advanced age is a known risk factor of poor outcomes for colitis, including Clostridium difficile infection (CDI). The present study compares the clinical outcomes of young and old patients hospitalized for CDI. METHODS: The clinical records of patients admitted from January 2007 to December 2013 with a diagnosis of CDI were analyzed. Patient baseline characteristics, clinical courses, and outcomes were compared with respect to age using a cut-off 65 years. RESULTS: Of the 241,391 inpatients registered during the study period, 225 (0.1%) with a diagnosis of CDI were included in the study. The mean patient age was 67.7 years. Seventy-two patients (32.0%) were younger than 65 years and 153 patients (68.0%) were 65 years old or more. The male to female ratio in the younger group was 0.8, and 0.58 in the older group. All 225 study subjects had watery diarrhea; six patients (8.3%) complained of bloody diarrhea in the young group and 21 patients (13.7%) in the old group (p=0.246). Right colon involvement was more common in the old group (23.5% vs. 42.7%, p=0.033). Furthermore, leukocytosis (41.7% vs. 67.3%, p=0.000), a CDI score of >= 3 points (77.8% vs. 89.5%, p=0.018), and hypoalbuminemia (58.3% vs. 76.5%, p=0.005) were more common in the old group. Failure to first line treatment was more common in the old group (17 [23.6%] vs. 58 [37.9%], p=0.034). CONCLUSIONS: Severe colitis and failure to first line treatment were significantly more common in patients age 65 years or more. More aggressive initial treatment should be considered for older CDI patients. PMID- 26907484 TI - [Role of Colonoscopy in Patients with Hematochezia]. AB - BACKGROUND/AIMS: Although colonoscopy is not indicated in patients with hematochezia, many surgeons, internists, and physicians are recommending colonoscopy for these patients in Korea. The aim of this study is to evaluate the diagnostic value of colonoscopy for patients with hematochezia. METHODS: We retrospectively reviewed the data of colonoscopy between January 2010 and December 2010. A total of 321 patients among 3,038 colonoscopies (10.6%) underwent colonoscopy to evaluate the cause of hematochezia. The patients with previous colorectal surgery (2) or polypectomy (5) were excluded. We analyzed endoscopic diagnoses. Advanced neoplastic polyps were defined as adenomas with villous histology or high grade dysplasia, or adenomas more than 10 mm in diameter. RESULTS: Hemorrhoid was the most common diagnosis (217 cases, 67.6%). Polyps were detected in 93 patients (29.0%), but advanced neoplastic polyps were found in only 14 cases (4.4%). Colorectal cancers were diagnosed in 18 patients (5.6%) including 14 rectal cancers. There was no cancer located above sigmoid descending junction. Diverticuli were detected in 41 patients (12.8%) but there was only one case of suspected diverticular bleeding. Colitis was diagnosed in 24 patients (7.5%). Other lesions included acute anal fissure, rectal tumor, stercoral ulcer, and radiation proctitis. CONCLUSIONS: The colonoscopy had little value in patients with hematochezia because the most pathologic lesions were located below sigmoid colon. The first choice of diagnosis in patients with hematochezia is sigmoidoscopy. PMID- 26907485 TI - Written Educational Material Relieves Anxiety after Endoscopic Biopsy: A Prospective Randomized Controlled Study. AB - BACKGROUND/AIMS: Patients who undergo endoscopic biopsy suffer anxiety until results are confirmed. This study assesses the effects of written educational material on the anxiety level of patients following endoscopic biopsy. METHODS: This study was a randomized controlled study trial with 83 patients divided into the following three groups: a biopsy group given written educational material prepared by our institution following the biopsy (intervention group, n=28), a biopsy group without written material (biopsy only group, n=25), and a control group without biopsy (control group, n=30). The anxiety level of each patient was evaluated three times using Spielberger's State-Trait Anxiety Inventory (STAI): for baseline at the first visit to our institution, at the day of endoscopy, one day later, and one week after the procedure. We compared baseline characteristics, STAI scores at each visit, and differences in STAI scores among the three groups. RESULTS: No difference was found in STAI score among groups at baseline and before and after the endoscopic procedure. However, the STAI-state score of the intervention group was slightly lower than biopsy only group one day post-procedure (40.3 +/- 7.7 vs. 43.9 +/- 7.1, p=0.135). The STAI-state score significantly decreased from pre- to post-procedure only in the intervention group (-2.75 +/- 6.1 vs. 0.92 +/- 4.0, p<0.027). CONCLUSIONS: Use of written educational material for patients having biopsy might lessen their anxiety level. PMID- 26907486 TI - [Inverted Hyperplastic Polyp in Stomach: A Case Report and Literature Review]. AB - An inverted hyperplastic polyp (IHP) found in stomach is rare and characterized by downward growth of hyperplastic mucosal component into the submucosa. Because of such characteristic, IHP can be misdiagnosed as subepithelial tumor or malignant tumor. In fact, adenocarcinoma was reported to have coexisted with gastric IHP in several previous reports. Because only 18 cases on gastric IHP have been reported in English and Korean literature until now, pathogenesis and clinical features of gastric IHP and correlation with adenocarcinoma have not been clearly established. Herein, we report a case of gastric IHP which was initially misdiagnosed as gastrointestinal stromal tumor and resected using endoscopic submucosal dissection. Literature review of previously published case reports on gastric IHP is also presented. PMID- 26907487 TI - Effective and Safe Use of Neostigmine in Treatment of Acute Kidney Injury Associated with Colonic Pseudo-obstruction after Cardiac Surgery. AB - Neostigmine can successfully decompress patients with acute colonic pseudo obstruction (ACPO) who are unresponsive to conservative therapy. However, neostigmine is contraindicated in renal failure, so it is underused in ACPO patients with renal failure who would be otherwise appropriate candidates. We described the first successfully treated case of acute kidney injury (AKI) with neostigmine in a patient with ACPO. A 72-year-old man who underwent a coronary artery bypass graft surgery 11 days prior presented to the emergency room with abdominal distension, peripheral edema, and dyspnea on exertion. Plain abdominal radiographs and abdomen computed tomography scan showed diffuse colonic dilatation without obstruction. Serum creatinine level was increased five-fold over baseline. We diagnosed the patient as ACPO with AKI. With conservative treatment, renal function failed to improve because the ACPO was not corrected. Administration of neostigmine rapidly resolved ACPO and renal function, avoiding more invasive procedures such as colonoscopic decompression and hemodialysis. Neostigmine appears to be an effective and safe treatment option for ACPO patients with renal failure. Prospective large-scale studies should be carried out to determine the safety and efficacy of neostigmine in ACPO patients with renal failure. PMID- 26907488 TI - Panenteritis as an Initial Presentation of Systemic Lupus Erythematosus. AB - Lupus enteritis is a rare, severe complication of systemic lupus erythematosus (SLE), needing prompt diagnosis and proper management. However, SLE rarely presents as lupus enteritis at the time of initial diagnosis. Thus, delayed diagnosis and misdiagnosis are common. We report a case of a 25-year-old woman with lupus panenteritis. The patient had multiple hospitalizations for abdominal pain, nausea, and diarrhea, initially without any other symptoms suggestive of SLE, but was later observed to have malar rash and oral ulcers. Laboratory investigations were compatible with SLE, including positive antinuclear antibody (1:320) with speckled pattern. CT revealed diffuse hypodense submucosal thickening of the stomach, the entire small bowel, colon, appendix, and rectum. Treatment with high-dose corticosteroids followed by maintenance therapy with mycophenolate mofetil, hydroxychloroquine, and azathioprine resulted in clinical improvement. Diagnosis of lupus enteritis requires a high index of suspicion given the low incidence and nonspecific clinical findings. PMID- 26907489 TI - [Fluoroscopy-induced Subacute Radiation Dermatitis in Patient with Hepatocellular Carcinoma]. AB - Radiation dermatitis can develop after fluoroscopy-guided interventional procedures. Cases of fluoroscopy-induced radiation dermatitis have been reported since 1996, mostly documented in the fields of radiology, cardiology and dermatology. Since diagnosis and treatment of fluoroscopy-induced radiation dermatitis can be difficult, high grade of suspicion is required. The extent of this reaction is determined by radiation dose, duration of exposure, type of procedure, and host factors and can be aggravated by concomitant use of photosensitizers. Follow-up is important after long and complicated procedures and efforts to minimize radiation exposure time will be necessary to prevent radiation dermatitis. Herein, we report a case of a 58-year-old man with hepatocellular carcinoma presenting with subacute radiation dermatitis after prolonged fluoroscopic exposure during transarterial chemoembolization and chemoport insertion. Physicians should be aware that fluoroscopy is a potential cause of radiation dermatitis. PMID- 26907490 TI - Corrigendum: Predictive Factors for Sustained Remission after Discontinuation of Antiviral Therapy in Patients with HBeAg-positive Chronic Hepatitis B. AB - This correction is being published to correct the error in Figure 4 in above article. PMID- 26907491 TI - Neuro-oncology family caregivers are at risk for systemic inflammation. AB - Prolonged periods of family caregiving can induce stress levels that may negatively influence caregiver health. However, the physiologic effect of psychological distress in oncology family caregivers has received little attention. Therefore we aimed to determine longitudinal profiles of inflammatory cytokines (IL-6 and IL-1ra) in neuro-oncology caregivers and identify associations between psychological distress and cytokine levels. Depressive symptoms, anxiety, caregiver burden and blood were collected from 108 adult caregivers at adult patients' diagnosis, 4-, 8-, and 12-months. Trajectory analyses of log transformed cytokine levels were performed. Multiple logistic regression analyses evaluated the impact of psychological distress on cytokine levels. For both cytokines, two distinct populations were identified, neither of which changed over time. High IL-1ra was associated with male caregivers with anxiety (OR = 1.7; 95 %CI 1.06-2.83) and obese caregivers (BMI = 40) who felt burdened due to disrupted schedules (OR = 1.3; 95 %CI 1.02-1.77). Conversely, caregivers with a healthy weight (BMI = 25) who felt burdened due to disrupted schedules were less likely to have high IL-1ra (OR = 0.71; 95 %CI 0.54-0.92). Caregivers <=30 years old with lower self-esteem from caregiving were 1.16 times (95 %CI 1.04-1.30) more likely to have high IL-6. Analysis demonstrated groups of family caregivers with high and low levels of systemic inflammation and these levels did not change longitudinally over the care trajectory. Poor physical health in family caregivers may have a negative impact on the burden placed on the healthcare system in general and on the well-being of neuro-oncology patients in particular. PMID- 26907492 TI - Recurrent glioblastoma: who receives tumor specific treatment and how often? AB - The recurrence of glioblastoma (rGBM) is inevitable and often short-term. Therefore, information on the prognosis and effectiveness of tumor-specific versus purely palliative approaches should be more in-depth than a mere list of available treatment options for patients in this situation. However, follow-up data on the course of the disease in unselected patient populations after completion of primary treatment are scarce. This single-center analysis investigated the rate and number of glioblastoma recurrences after initial radiotherapy in 189 consecutive GM patients, focusing on the incidence of early death and the frequency of tumor-specific treatment (TST) versus best-supportive care (BSC) as well as the outcomes for the different approaches. In 61 % of initial population first recurrence (rGBM) could be determined by histology or imaging. 47 % received TST. 58 % of the patients with rGBM and TST were diagnosed with a second recurrence. Up to five recurrences were treated. 35-45 % of patients died before undergoing imaging studies to confirm the next recurrence. Multivariate analysis identified male sex and KPS score as independent factors (p < 0.01) for the choice of TST over BSC. Median overall survival from the diagnosis of first recurrence was 267 days in the TST group versus 65 days in patients receiving BSC (p < 0.0001). Nearly half of all rGBM patients received second-line TST, but a remarkably high proportion died early. Gender and KPS played a role in the choice of TST over BSC for recurrence treatment. PMID- 26907493 TI - Andes Hantavirus-Infection of a 3D Human Lung Tissue Model Reveals a Late Peak in Progeny Virus Production Followed by Increased Levels of Proinflammatory Cytokines and VEGF-A. AB - Andes virus (ANDV) causes hantavirus pulmonary syndrome (HPS), a severe acute disease with a 40% case fatality rate. Humans are infected via inhalation, and the lungs are severely affected during HPS, but little is known regarding the effects of ANDV-infection of the lung. Using a 3-dimensional air-exposed organotypic human lung tissue model, we analyzed progeny virus production and cytokine-responses after ANDV-infection. After a 7-10 day period of low progeny virus production, a sudden peak in progeny virus levels was observed during approximately one week. This peak in ANDV-production coincided in time with activation of innate immune responses, as shown by induction of type I and III interferons and ISG56. After the peak in ANDV production a low, but stable, level of ANDV progeny was observed until 39 days after infection. Compared to uninfected models, ANDV caused long-term elevated levels of eotaxin-1, IL-6, IL 8, IP-10, and VEGF-A that peaked 20-25 days after infection, i.e., after the observed peak in progeny virus production. Notably, eotaxin-1 was only detected in supernatants from infected models. In conclusion, these findings suggest that ANDV replication in lung tissue elicits a late proinflammatory immune response with possible long-term effects on the local lung cytokine milieu. The change from an innate to a proinflammatory response might be important for the transition from initial asymptomatic infection to severe clinical disease, HPS. PMID- 26907494 TI - Risk and Control of Mosquito-Borne Diseases in Southeast Asian Rubber Plantations. AB - Unprecedented economic growth in Southeast Asia (SEA) has encouraged the expansion of rubber plantations. This land-use transformation is changing the risk of mosquito-borne diseases. Mature plantations provide ideal habitats for the mosquito vectors of malaria, dengue, and chikungunya. Migrant workers may introduce pathogens into plantation areas, most worryingly artemisinin-resistant malaria parasites. The close proximity of rubber plantations to natural forest also increases the threat from zoonoses, where new vector-borne pathogens spill over from wild animals into humans. There is therefore an urgent need to scale up vector control and access to health care for rubber workers. This requires an intersectoral approach with strong collaboration between the health sector, rubber industry, and local communities. PMID- 26907495 TI - N-Carbamylglutamate Is an Effective Treatment for Acute Neonatal Hyperammonaemia in a Patient with Methylmalonic Aciduria. AB - N-carbamylglutamate (NCG) has been used in combination with ammonia scavengers (sodium benzoate, sodium phenylbutyrate) and dialysis to treat hyperammonaemia in methylmalonic aciduria (MMA). The sole use of NCG for acute neonatal hyperammonaemia secondary to MMA is demonstrated in a neonate presenting at day 9 with encephalopathy, severe metabolic acidosis, hyperammonaemia (1,089 MUmol/l), ketonuria and urinary methylmalonic acids. Emergency treatment included discontinuing protein feeds, providing high calories, carnitine and hydroxocobalamin. NCG 200 mg given at 0 and 90 min decreased plasma ammonia dramatically from 1,089 to 567 umol/l at 90 min and further to 236 umol/l at 6 h. Normalisation of ammonia was achieved at 12 h with two further doses of NCG 100 mg. This allowed for early re-institution of feeds at 14 h, followed by metabolic stabilization and recovery. Due to the effectiveness of NCG in this case, the use of the more invasive conventional ammonia-lowering therapeutic options could be avoided. PMID- 26907496 TI - The Proteomics of Intrathecal Analgesic agents for Chronic Pain. AB - Chronic pain remains a challenging clinical problem with a growing socio-economic burden for the state. Its prevalence is high and many of the patients are of work age. Our knowledge regarding the pathophysiology of chronic pain is poor. The consensus view is that the central nervous system plays a key role in the persistence of pain after an initiating event has long ceased. However the specifics of this biological response to an initiating event remains unclear. There is a growing body of evidence to support the concept that a central neuroimmune response is initiated and a number of small peptides have been implicated in this process following cerebrospinal fluid analysis in patients with chronic pain. This central biosynthetic peptide response leads to a process called central sensitization. Therapy is aimed at modulating and even inhibiting this response. However current pharmacological therapeutic options are limited in efficacy with significant deleterious side effect profiles. Proteomic studies extend single molecule analysis by identifying the components of biological networks and pathways and defining their interactions. This tool offers the potential to provide a molecular overview of the biological processes involved in chronic pain. It will also facilitate examination of gene-drug interactions. This technique offers a mechanism of defining the central biological responses that result in chronic pain and this information may facilitate the development of better therapies. PMID- 26907497 TI - A survey of burn professionals regarding the mental health services available to burn survivors in the United States and United Kingdom. AB - This investigation surveyed burn health professionals in the UK and US to investigate the psychosocial issues facing burn survivors and the psychological services available to them through their burns service. METHODS: One hundred and sixty six burn care professionals (132 from the United States and 34 from the United Kingdom) from 76 different hospitals (60 in the US and 16 in the UK) completed an online survey. Mental health practitioners (MHPs) answered questions regarding their psychotherapy practice with burn survivors. RESULTS: Respondents reported that psychosocial issues are common among burn survivors. Burn teams in the UK were more likely than those in the US to include psychologists, but social workers were more common in the US. Participants reported that routine screening for psychosocial issues was more common in the UK than the US, and indicated it was easier for burn survivors to access mental health care after discharge in the UK. Burn services in both countries routinely referred burn survivors to support organizations such as the Phoenix Society or Changing Faces. The preferred mental health treatment modality in the UK was psychotherapy without medications. Reported psychotropic medications use was more common in the US. MHPs had two primary orientations - eclectic and cognitive behavioral therapy. Among MHPs there was a modest tendency to favor evidence-based interventions. DISCUSSION: The provision of mental health services varies between these two countries. Creating international standards for assessing and treating psychosocial complications of burns could facilitate the improvement of burn mental health services. PMID- 26907498 TI - Genome Resequencing Identifies Unique Adaptations of Tibetan Chickens to Hypoxia and High-Dose Ultraviolet Radiation in High-Altitude Environments. AB - Tibetan chicken, unlike their lowland counterparts, exhibit specific adaptations to high-altitude conditions. The genetic mechanisms of such adaptations in highland chickens were determined by resequencing the genomes of four highland (Tibetan and Lhasa White) and four lowland (White Leghorn, Lindian, and Chahua) chicken populations. Our results showed an evident genetic admixture in Tibetan chickens, suggesting a history of introgression from lowland gene pools. Genes showing positive selection in highland populations were related to cardiovascular and respiratory system development, DNA repair, response to radiation, inflammation, and immune responses, indicating a strong adaptation to oxygen scarcity and high-intensity solar radiation. The distribution of allele frequencies of nonsynonymous single nucleotide polymorphisms between highland and lowland populations was analyzed using chi-square test, which showed that several differentially distributed genes with missense mutations were enriched in several functional categories, especially in blood vessel development and adaptations to hypoxia and intense radiation. RNA sequencing revealed that several differentially expressed genes were enriched in gene ontology terms related to blood vessel and respiratory system development. Several candidate genes involved in the development of cardiorespiratory system (FGFR1, CTGF, ADAM9, JPH2, SATB1, BMP4, LOX, LPR, ANGPTL4, and HYAL1), inflammation and immune responses (AIRE, MYO1F, ZAP70, DDX60, CCL19, CD47, JSC, and FAS), DNA repair, and responses to radiation (VCP, ASH2L, and FANCG) were identified to play key roles in the adaptation to high-altitude conditions. Our data provide new insights into the unique adaptations of highland animals to extreme environments. PMID- 26907499 TI - Atlas of Cryptic Genetic Relatedness Among 1000 Human Genomes. AB - A novel computational method for detecting identical-by-descent (IBD) chromosomal segments between sequenced genomes is presented. It utilizes the distribution patterns of very rare genetic variants (vrGVs), which have minor allele frequencies <0.2%. Contrary to the existing probabilistic approaches our method is rather deterministic, because it considers a group of very rare events which cannot happen together only by chance. This method has been applied for exhaustive computational search of shared IBD segments among 1,092 sequenced individuals from 14 populations. It demonstrated that clusters of vrGVs are unique and powerful markers of genetic relatedness, that uncover IBD chromosomal segments between and within populations, irrespective of whether divergence was recent or occurred hundreds-to-thousands of years ago. We found that several IBD segments are shared by practically any possible pair of individuals belonging to the same population. Moreover, shared short IBD segments (median size 183 kb) were found in 10% of inter-continental human pairs, each comprising of a person from sub-Saharan Africa and a person from Southern Europe. The shortest shared IBD segments (median size 54 kb) were found in 0.42% of inter-continental pairs composed of individuals from Chinese/Japanese populations and Africans from Kenya and Nigeria. Knowledge of inheritance of IBD segments is important in clinical case-control and cohort studies, since unknown distant familial relationships could compromise interpretation of collected data. Clusters of vrGVs should be useful markers for familial relationship and common multifactorial disorders. PMID- 26907501 TI - Drugs for smoking cessation. PMID- 26907502 TI - Cardiovascular fitness is improved post-stroke with upper-limb Wii-based Movement Therapy but not dose-matched constraint therapy. AB - INTRODUCTION: Post-stroke cardiovascular fitness is typically half that of healthy age-matched people. Cardiovascular deconditioning is a risk factor for recurrent stroke that may be overlooked during routine rehabilitation. This study investigated the cardiovascular responses of two upper limb rehabilitation protocols. METHODS: Forty-six stroke patients completed a dose-matched program of Wii-based Movement Therapy (WMT) or modified Constraint-induced Movement Therapy (mCIMT). Heart rate and stepping were recorded during early (day 2)- and late (day 12-14)-therapy. Pre- and post-therapy motor assessments included the Wolf Motor Function Test and 6-min walk. RESULTS: Upper limb motor function improved for both groups after therapy (WMT p = 0.003, mCIMT p = 0.04). Relative peak heart rate increased from early- to late-therapy WMT by 33% (p < 0.001) and heart rate recovery (HRR) time was 40% faster (p = 0.04). Peak heart rate was higher and HRR faster during mCIMT than WMT, but neither measure changed during mCIMT. Stepping increased by 88% during Wii-tennis (p < 0.001) and 21% during Wii-boxing (p = 0.045) while mCIMT activities were predominantly sedentary. Six-min walk distances increased by 8% (p = 0.001) and 4% (p = 0.02) for WMT and mCIMT, respectively. DISCUSSION: Cardiovascular benefits were evident after WMT as both a cardiovascular challenge and improved cardiovascular fitness. The peak heart rate gradient across WMT activities suggests this therapy can be further individualized to address cardiovascular needs. The mCIMT data suggest a cardiovascular stress response. CONCLUSIONS: This is the first study to demonstrate a cardiovascular benefit during specifically targeted upper limb rehabilitation. Thus, WMT not only improves upper limb motor function but also improves cardiovascular fitness. PMID- 26907500 TI - Comprehensive Genomic Analysis and Expression Profiling of the NOX Gene Families under Abiotic Stresses and Hormones in Plants. AB - Plasma membrane NADPH oxidases (NOXs) are key producers of reactive oxygen species under both normal and stress conditions in plants and they form functional subfamilies. Studies of these subfamilies indicated that they show considerable evolutionary selection. We performed a comparative genomic analysis that identified 50 ferric reduction oxidases (FRO) and 77 NOX gene homologs from 20 species representing the eight major plant lineages within the supergroup Plantae: glaucophytes, rhodophytes, chlorophytes, bryophytes, lycophytes, gymnosperms, monocots, and eudicots. Phylogenetic and structural analysis classified these FRO and NOX genes into four well-conserved groups represented as NOX, FRO I, FRO II, and FRO III. Further analysis of NOXs of phylogenetic and exon/intron structures showed that single intron loss and gain had occurred, yielding the diversified gene structures during the evolution of NOXs family genes and which were classified into four conserved subfamilies which are represented as Sub.I, Sub.II, Sub.III, and Sub.IV. Additionally, both available global microarray data analysis and quantitative real-time PCR experiments revealed that the NOX genes in Arabidopsis and rice (Oryza sativa) have different expression patterns in different developmental stages, various abiotic stresses and hormone treatments. Finally, coexpression network analysis of NOX genes in Arabidopsis and rice revealed that NOXs have significantly correlated expression profiles with genes which are involved in plants metabolic and resistance progresses. All these results suggest that NOX family underscores the functional diversity and divergence in plants. This finding will facilitate further studies of the NOX family and provide valuable information for functional validation of this family in plants. PMID- 26907503 TI - Longitudinal Treatment Patterns and Associated Outcomes in Patients With Newly Diagnosed Systemic Lupus Erythematosus. AB - PURPOSE: The treatment of systemic lupus erythematosus (SLE) is complex, with a wide range of drugs commonly prescribed. The aims of this study were to identify longitudinal treatment patterns in patients with incident SLE and to estimate the associations of treatment patterns with clinical and economic outcomes. METHODS: This retrospective, observational cohort study used a US managed care claims database to identify patients with newly diagnosed SLE and 4-year treatment follow-up. Patients were aged >= 18 years, with continuous medical and pharmacy benefits for 12 months before and 48 months after the index date (first medical claim with a diagnosis of SLE). Longitudinal treatment patterns were grouped using a k-means cluster analysis. Therapies were included in the cluster analysis if the mean number of prescriptions in each year was >= 0.05. Clinical and economic outcomes were compared across clusters using multivariate regression analyses. FINDINGS: Data from 1611 patients with incident SLE were analyzed (91.4% women; mean [SD] age, 44.5 [9.5] years; 56.2% managed primarily by a specialist). Hydroxychloroquine and corticosteroids were the most commonly prescribed therapies; methotrexate, azathioprine, and mycophenolate mofetil also met the criteria for inclusion in the cluster analysis. Ten treatment clusters were identified; the most common was minimally treated patients (42.8%). Hydroxychloroquine monotherapy, corticosteroid monotherapy, and corticosteroid/hydroxychloroquine combination therapy were received by 34.0%, 11.2%, and 7.8% of patients, respectively. Methotrexate or azathioprine with a corticosteroid/hydroxychloroquine were received by 4.2% of patients. Changes in therapy, except discontinuations, were rare. Compared with the minimally treated cluster, those that received corticosteroid monotherapy (mean dose, >12.0 mg/d) had poorer clinical and economic outcomes; the hydroxychloroquine-monotherapy cluster had similar or better outcomes; and patients who received a corticosteroid/hydroxychloroquine with or without methotrexate or azathioprine demonstrated outcomes that were poorer but that appeared better than those with corticosteroid monotherapy. SLE-related visits with a nonspecialist were common (~45%) and remained unchanged over time despite better clinical and economic outcomes associated with specialist visits. IMPLICATIONS: This study utilized cluster analysis, an unsupervised machine-learning method, to systematically discern treatment patterns over 4 years and to estimate outcomes associated with the identified treatment patterns. The results suggest that minimal treatment is the most common approach in patients with newly diagnosed SLE. Clinical and economic outcomes are poorest with corticosteroid monotherapy but may improve with the addition of hydroxychloroquine and/or an immunosuppressive agent. A large proportion of SLE care is provided by nonspecialists despite the potential benefits of involving a specialist. PMID- 26907504 TI - Cost-effectiveness of Bedaquiline for the Treatment of Multidrug-resistant Tuberculosis in the Republic of Korea. AB - PURPOSE: Bedaquiline is a new drug used for the treatment of multidrug-resistant tuberculosis (MDR-TB). This study aimed to evaluate the cost-effectiveness of adding bedaquiline to a standard regimen (SR) for treating patients with MDR-TB, including extensively drug-resistant (XDR)-TB, in the Republic of Korea. METHODS: A cohort-based decision-analytic model developed in a previously published study from the United Kingdom was used, with a 20-year time horizon and a 5% discount rate for cost and effectiveness, to evaluate the incremental cost-effectiveness ratios of bedaquiline + SR and SR only. The key parameters regarding the clinical data were available via the published Phase II trial of bedaquiline. Additional parameters for recurrence, cure status, loss to follow-up, surgery, death, cost, and health utility were based on Korean data if available; otherwise the international literature data were applied. Univariate and probabilistic sensitivity analyses were conducted. FINDINGS: Based on the analysis, a patient on bedaquiline + SR would gain 1.20 quality-adjusted life-years (QALYs) at 13,961,659 Korean won (KRW) (1100 KRW = US $1) of additional cost compared with a patient administered SR only, with an incremental cost/utility ratio of 11,638,656 KRW/QALY. Bedaquiline + SR had an 80% probability of being cost effective, at a willingness-to-pay threshold of 26 million KRW, compared with SR only. IMPLICATIONS: The results of this study suggest that, in the Republic of Korea, bedaquiline, as a part of combination therapy with SR, is a cost-effective option for the treatment of MDR-TB (including XDR-TB) compared with SR only. PMID- 26907506 TI - Robot-Assisted Radical Cystectomy with Total Intracorporeal Urinary Diversion: Comparative Analysis with Extracorporeal Urinary Diversion. AB - PURPOSE: To compare the perioperative outcomes, postoperative complications, and early oncologic outcomes of intracorporeal urinary diversion (ICUD) with those of extracorporeal urinary diversion (ECUD) following robot-assisted radical cystectomy (RARC) performed by a single surgeon at a tertiary referral hospital. MATERIALS AND METHODS: We reviewed a prospectively maintained, institutional review board-approved database of 70 patients treated with RARC and pelvic lymph node (LN) dissection for bladder cancer performed from 2007 through 2014. Data were collected for 64 patients who underwent either ICUD or ECUD. RESULTS: Thirty eight patients underwent ECUD, and the remaining 26 underwent ICUD. Urinary diversion was performed extracorporeally in the first 37 cases and performed intracorporeally thereafter. There were no significant differences in patient characteristics between the ECUD and ICUD groups. Mean total operative time was 468 minutes for ECUD and 581 minutes for ICUD (P < .05). Mean estimated blood loss was 265 and 148 mL, respectively (P < .05). Minor and total complication rates for patients with the ECUD were higher than in patients with the ICUD (minor: 47.4% vs. 15.4%; total: 57.9% vs. 30.8%; P < .05). All patients showed negative surgical margin, while 21% in the ECUD group and 26.9% in the ICUD group had pathologic stage T3 or T4 (P > .05). The mean LN yield was 23.2 and 31.8, respectively (P < .05). CONCLUSIONS: From our experience, the results show that ICUD after RARC can be successful, with the benefits of decreased blood loss and lower transfusion and complication rates than ECUD. A larger series and long-term follow-up data will be necessary to support our results. PMID- 26907507 TI - [Cytomegalovirus infection in pregnancy: A fourteen-year review in a pluridisciplinary prenatal center]. AB - BACKGROUND: Cytomegalovirus (CMV) is the most frequent cause of congenital infection. The aim of this research was to describe the decision-process for parents to pursue gestation or to ask medical abortion after materno-fetal CMV infection. OBJECTIVES: The primary objective of this study is to analyze the decision-process for parents after materno-fetal infection with positive PCR after amniocentesis, to ask or not a medical termination of pregnancy (TOP). The secondary objectives are to compare ours results with literature review (pronostics factors, ultrasonographic signs and neonatal symptomatology). MATERIALS AND METHODS: This is a retrospective study, focused with a pluridisciplinary materno-fetal prenatal medical center, during a 14-year long period. Only 15 patients have been included in the study. They have been divided in 2 groups (the first group who decided to ask a TOP [n=8] and the second group who pursued the gestation [n=7]). We compare respectively their clinical, ultrasonographic, or other imagery and biological paths, before and after the birth. RESULTS: A total of 15/16 patients had a CMV seroconversion before 20weeks of gestation. The only infection after 20SA did not have any sequelae. The ultrasonography and the cerebral fetal MRI appeared to be very complementary for the assesment of brain injury, which is more frequent in the group with a TOP (7/8 versus 4/7). Three neonates out of 4 who had a cord positive viral blood load at birth are presenting neonatal symptoms, 2 of them will have severe brain and hearing injuries, the fourth one had no sequelae after 6months of life. CONCLUSION: Only the presence of ultrasonographic major brain damages, and confirmation with MRI, had a pejorative value as prognosis factor suggesting to patients to choose a TOP. Nevertheless, other ways of research are possible to assess the prognostic value in this difficult prenatal diagnosis process. PMID- 26907508 TI - Positive Surgical Margins Increase Risk of Recurrence after Partial Nephrectomy for High Risk Renal Tumors. AB - PURPOSE: The clinical significance of a positive surgical margin after partial nephrectomy remains controversial. The association between positive margin and risk of disease recurrence in patients with clinically localized renal neoplasms undergoing partial nephrectomy was evaluated. MATERIALS AND METHODS: A retrospective multi-institutional review of 1,240 patients undergoing partial nephrectomy for clinically localized renal cell carcinoma between 2006 and 2013 was performed. Recurrence-free survival was estimated using the Kaplan-Meier method and evaluated as a function of positive surgical margin with the log rank test and Cox models adjusting for tumor size, grade, histology, pathological stage, focality and laterality. The relationship between positive margin and risk of relapse was evaluated independently for pathological high risk (pT2-3a or Fuhrman grades III-IV) and low risk (pT1 and Fuhrman grades I-II) groups. RESULTS: A positive surgical margin was encountered in 97 (7.8%) patients. Recurrence developed in 69 (5.6%) patients during a median followup of 33 months, including 37 (10.3%) with high risk disease (eg pT2-pT3a or Fuhrman grade III IV). A positive margin was associated with an increased risk of relapse on multivariable analysis (HR 2.08, 95% CI 1.09-3.97, p=0.03) but not with site of recurrence. In a stratified analysis based on pathological features, a positive surgical margin was significantly associated with a higher risk of recurrence in cases considered high risk (HR 7.48, 95% CI 2.75-20.34, p <0.001) but not low risk (HR 0.62, 95% CI 0.08-4.75, p=0.647). CONCLUSIONS: Positive surgical margins after partial nephrectomy increase the risk of disease recurrence, primarily in patients with adverse pathological features. PMID- 26907509 TI - Measuring and Predicting Patient Dissatisfaction after Anterior Urethroplasty Using Patient Reported Outcomes Measures. AB - PURPOSE: Subjective measures of success after urethroplasty have become increasingly valuable in postoperative monitoring. We examined patient reported satisfaction following anterior urethroplasty using objective measures as a proxy for success. MATERIALS AND METHODS: Men 18 years old or older with urethral strictures undergoing urethroplasty were prospectively enrolled in a longitudinal, multi-institutional urethroplasty outcomes database. Preoperative and postoperative assessment included questionnaires to assess lower urinary tract symptoms, pain, satisfaction and sexual health. Analyses controlling for stricture recurrence (defined as the inability to traverse the reconstructed urethra with a flexible cystoscope) were performed to determine independent predictors of dissatisfaction. RESULTS: At a mean followup of 14 months we found a high 89.4% rate of overall postoperative satisfaction in 433 patients and a high 82.8% rate in those who would have chosen the operation again. Men with cystoscopic recurrence were more likely to report dissatisfaction (OR 4.96, 95% CI 2.07-11.90) and men reporting dissatisfaction had significantly worse uroflowmetry measures (each p <0.02). When controlling for recurrence, multivariate analysis revealed that urethra and bladder pain (OR 1.71, 95% CI 1.05-2.77 and OR 2.74, 95% CI 1.12-6.69, respectively), a postoperative decrease in sexual activity (OR 4.36, 95% CI 2.07-11.90) and persistent lower urinary tract symptoms (eg straining to urinate OR 3.23, 1.74-6.01) were independent predictors of dissatisfaction. CONCLUSIONS: Overall satisfaction after anterior urethroplasty is high and traditional measures of surgical success strongly correlate with satisfaction. However, independently of the anatomical appearance of the reconstructed urethra, postoperative pain, sexual dysfunction and persistent lower urinary tract symptoms were predictors of patient dissatisfaction. PMID- 26907511 TI - How Best to Measure and Test for Androgen Deficiency. PMID- 26907510 TI - Somatic Comorbidity in Women with Overactive Bladder Syndrome. AB - PURPOSE: We explore the influence of co-occurring somatic illnesses on prevalent overactive bladder in women of premenopausal age. MATERIALS AND METHODS: Data for the present study were derived from a nationwide survey on complex diseases among all twins in the Swedish Twin Registry born 1959 to 1985. The present study was limited to female twins participating in the survey (12,850). Generalized estimating equations were used to estimate odds ratios with 95% CIs. Environmental and genetic influences were assessed in co-twin control analysis. RESULTS: Generalized estimating equations analysis showed a significant association between overactive bladder and migraine (OR 1.34, 95% CI 1.15-1.57), fibromyalgia (1.83, 1.54-2.18), chronic fatigue (1.81, 1.49-2.19) and eating disorders (1.56, 1.24-1.96). There was also a significant association with allergic disorders including asthma (1.24, 1.01-1.52) and eczema (1.22, 1.04 1.43). Among reproductive disorders, urinary tract infections (1.60, 1.40-1.84), dysmenorrhea (1.53, 1.33-1.76) and pelvic pain (1.60, 1.31-1.94) showed the strongest association with overactive bladder. Results from co-twin control analysis indicated that the significant associations observed in generalized estimating equations analysis were influenced by environmental and genetic factors without a common pathway model. CONCLUSIONS: Our results suggest a multifactorial and complex pathogenesis of overactive bladder in which associations between various somatic illnesses and overactive bladder may be affected by environmental and genetic factors. PMID- 26907512 TI - Second-line angiogenesis inhibition in metastatic colorectal cancer patients: Straightforward or overcrowded? AB - Although the number of therapeutic options targeting tumour angiogenesis is becoming increasingly relevant, the question of the optimal choice for second line anti-angiogenic inhibition in combination with chemotherapy for metastatic colorectal cancer patients remains largely unanswered. In fact the lack of head to head comparison between consolidated options such as bevacizumab and new treatment alternatives such as aflibercept and ramucirumab makes the selection in the clinical practice challenging, particularly when the patient has already received an anti-angiogenic-based combination up-front. In the following pages we described the biological scenario validating second-line angiogenesis inhibition in colorectal cancer along with potential mechanism of resistance. We also critically described the available evidence recommending the use of the bevacizumab, aflibercept and ramucirumab in this setting with the final aim to guide the choice in the clinical practice. PMID- 26907513 TI - Hypoglycemia Prevention and User Acceptance of an Insulin Pump System with Predictive Low Glucose Management. AB - BACKGROUND: The MiniMed 640G sensor-augmented insulin pump system (Medtronic, Inc., Northridge, CA) can automatically suspend insulin delivery in advance of predicted hypoglycemia and restart it upon recovery. The aims of this analysis were to determine the rate at which predicted hypoglycemia was avoided with this strategy, as well as to assess user acceptance of the system and its insulin management features. SUBJECTS AND METHODS: Forty subjects with type 1 diabetes used the system for 4 weeks. We retrospectively evaluated performance of the system, using downloaded pump and sensor data, and evaluated user acceptance via questionnaires. RESULTS: There were 2,322 suspend before low events (2.1 per subject-day). The mean (+/- SD) duration of pump suspension events was 56.4 +/- 9.6 min, and the mean subsequent sensor glucose (SG) nadir was 71.8 +/- 5.2 mg/dL. SG values following 1,930 (83.1%) of the predictive suspensions did not reach the preset low limit. Nadir SG values of <=50 and <=60 mg/dL were seen in 207 (8.9%) and 356 (15.3%) of the predictive suspensions, respectively. Blood glucose (BG) and SG values before and during the study were comparable (P > 0.05). The mean absolute relative difference between paired SG and BG values was 10.9 +/- 13.8%. Subjects felt confident using the system, agreed that it helped protect them from hypoglycemia, and wished to continue using it. CONCLUSIONS: Automatic insulin pump suspension as implemented in the MiniMed 640G system can help patients avoid hypoglycemia, without significantly increasing hyperglycemia. PMID- 26907514 TI - Time-dependent dose-response relation for absence of vaginal elasticity after gynecological radiation therapy. AB - BACKGROUND AND PURPOSE: To investigate the dose-response relation between the dose to the vagina and the patient-reported symptom 'absence of vaginal elasticity' and how time to follow-up influences this relation. MATERIAL AND METHODS: The study included 78 long-term gynecological cancer survivors treated between 1991 and 2003 with external beam radiation therapy. Of those, 24 experienced absence of vaginal elasticity. A normal tissue complication model is introduced that takes into account the influence of time to follow-up on the dose response relation and the patient's age. The best estimates of the dose-response parameters were calculated using Probit, Probit-Relative Seriality (RS) and Probit-time models. Log likelihood (LL) values and the Akaike Information Criterion (AIC) were used to evaluate the model fit. RESULTS: The dose-response parameters for 'absence of vaginal elasticity' according to the Probit and Probit time models with the 68% Confidence Intervals (CI) were: LL=-39.8, D50=49.7 (47.2 52.4) Gy, gamma50=1.40 (1.12-1.70) and LL=-37.4, D50=46.9 (43.5-50.9) Gy, gamma50=1.81 (1.17-2.51) respectively. CONCLUSIONS: The proposed model, which describes the influence of time to follow-up on the dose-response relation, fits our data best. Our data indicate that the steepness of the dose-response curve of the dose to the vagina and the symptom 'absence of vaginal elasticity' increases with time to follow-up, while D50 decreases. PMID- 26907516 TI - Aflibercept for the treatment of diabetic macular edema. AB - Diabetic macular edema (DME) is an accumulation of fluid in the central retina, secondary to vascular-leakage from diabetic vascular damage. DME and other ophthalmic sequela of diabetes are the leading cause of blindness in 20 to 74 year-olds. The development of VEGF-inhibitors (anti-VEGF) has revolutionized DME treatment improving the clinician's ability to remove excess fluid from the macula, improving visual-acuity. Aflibercept is an anti-VEGF agent made of a recombinant fusion protein (consisting of VEGF receptors 1 and 2 extracellular domains) fused with the Fc-portion of human-IgG1, which binds both VEGF isoforms A and B, and placental growth factor. Phase III clinical trials and published scientific studies have demonstrated the efficacy of intravitreal aflibercept injection in the treatment of DME. PMID- 26907515 TI - Unique antitumor property of the Mg-Ca-Sr alloys with addition of Zn. AB - In clinical practice, tumor recurrence and metastasis after orthopedic prosthesis implantation is an intensely troublesome matter. Therefore, to develop implant materials with antitumor property is extremely necessary and meaningful. Magnesium (Mg) alloys possess superb biocompatibility, mechanical property and biodegradability in orthopedic applications. However, whether they possess antitumor property had seldom been reported. In recent years, it showed that zinc (Zn) not only promote the osteogenic activity but also exhibit good antitumor property. In our present study, Zn was selected as an alloying element for the Mg 1Ca-0.5Sr alloy to develop a multifunctional material with antitumor property. We investigated the influence of the Mg-1Ca-0.5Sr-xZn (x = 0, 2, 4, 6 wt%) alloys extracts on the proliferation rate, cell apoptosis, migration and invasion of the U2OS cell line. Our results show that Zn containing Mg alloys extracts inhibit the cell proliferation by alteration the cell cycle and inducing cell apoptosis via the activation of the mitochondria pathway. The cell migration and invasion property were also suppressed by the activation of MAPK (mitogen-activated protein kinase) pathway. Our work suggests that the Mg-1Ca-0.5Sr-6Zn alloy is expected to be a promising orthopedic implant in osteosarcoma limb-salvage surgery for avoiding tumor recurrence and metastasis. PMID- 26907517 TI - [Central giant cell granuloma in children: Presentation of different therapeutic options]. AB - Central giant cell granuloma (CGCG) is a benign tumor that may be subdivided in a non-aggressive form and an aggressive form. In aggressive forms, tumor size and high recurrence risk need large surgical resections. In order to minimize surgical morbidity, especially in children, medical treatments acting on the tumor proliferation are currently being assessed: steroids (triamcinolone), anti osteoclastic drugs (calcitonine, alendronate, denosumab), anti-angiogenic drugs (interferon alpha). However to date, there is no evidence for any superiority of medical over surgical treatment. Complete response is rarely obtained and additional surgery is often necessary to remove the tumor in case of tumor progression, to remove a remnant or to remodel bone. Moreover, these drugs have frequent local or systemic side effects such as osteonecrosis and growth deficiencies. PMID- 26907518 TI - Novel pharmacological therapies for irritable bowel syndrome. AB - Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder, which represents a major cost to healthcare services. Current pharmacological treatment includes fibre supplements, antispasmodics, laxatives, loperamide and antidepressants. This article reviews the novel pharmacological treatments already or recently approved for patients with IBS-C (lubiprostone, linaclotide) and IBS-D (alosetron, ramosetron, rifaximin, eluxadoline). Furthermore, results for drugs in development (plecanatide, ibudutant and ebastine) or used in chronic constipation or for other indications, with potential application in IBS (prucalopride, elobixibat, mesalazine, ondansetron and colesevelam) are also reviewed. PMID- 26907519 TI - Epilogue. PMID- 26907520 TI - Spectroscopic Investigation of the Carotenoid Deoxyperidinin: Direct Observation of the Forbidden S0 -> S1 Transition. AB - This paper presents a spectroscopic investigation of deoxyperidinin, a synthetic peridinin analogue in which the carbonyl functional group in peridinin was replaced by a nonconjugated methylene group. Steady-state and ultrafast time resolved absorption and fluorescence spectroscopic experiments are carried out on deoxyperidinin in n-hexane and acetonitrile at room temperature and in 2 methyltetrahydrofuran at 77 K. The spectra of deoxyperidinin have higher vibronic resolution compared to those of peridinin. The higher resolution is due to a substantial reduction in both molecular conformational disorder and inhomogeneous broadening of the spectra of deoxyperidinin compared to peridinin. Features in the steady-state absorption spectrum of deoxyperidinin that are not evident in the spectrum of peridinin are unambiguously assigned to the forbidden S0 (1(1)Ag( )) -> S1 (2(1)Ag(-)) absorption transition. The characteristics of both the steady-state and time-resolved spectra are interpreted using EOM-CCSD, SAC-CI, and MNDO-PSDCI quantum computational formalisms that provided a theoretical framework for understanding the photophysical properties of the molecules. PMID- 26907521 TI - Endogenous APP accumulates in synapses after BACE1 inhibition. AB - BACE1-mediated cleavage of APP is a pivotal step in the production of the Alzheimer related Abeta peptide and inhibitors of BACE1 are currently in clinical development for the treatment of Alzheimer disease (AD). While processing and trafficking of APP has been extensively studied in non-neuronal cells, the fate of APP at neuronal synapses and in response to reduced BACE1 activity has not been fully elucidated. Here we examined the consequence of reduced BACE1 activity on endogenous synaptic APP by monitoring N- and C-terminal APP epitopes by immunocytochemistry. In control rodent primary hippocampal neuron cultures, labeling with antibodies directed to N-terminal APP epitopes showed a significant overlap with synaptic vesicle markers (SV2 or synaptotagmin). In contrast, labeling with antibodies directed to C-terminal epitopes of APP showed only a limited overlap with these proteins. In neurons derived from BACE1-deficient mice, and in control neurons treated with a BACE1 inhibitor, both the N-terminal and the C-terminal APP labeling overlapped significantly with synaptic vesicle markers. Moreover, BACE1 inhibition increased the proximity between the APP C terminus and SV2 as shown by a proximity ligation assay. These results, together with biochemical observations, indicate that BACE1 can regulate the levels of full-length APP at neuronal synapses. PMID- 26907522 TI - Neuromagnetic evidence that the right fusiform face area is essential for human face awareness: An intermittent binocular rivalry study. AB - When and where the awareness of faces is consciously initiated is unclear. We used magnetoencephalography to probe the brain responses associated with face awareness under intermittent pseudo-rivalry (PR) and binocular rivalry (BR) conditions. The stimuli comprised three pictures: a human face, a monkey face and a house. In the PR condition, we detected the M130 component, which has been minimally characterized in previous research. We obtained a clear recording of the M170 component in the fusiform face area (FFA), and found that this component had an earlier response time to faces compared with other objects. The M170 occurred predominantly in the right hemisphere in both conditions. In the BR condition, the amplitude of the M130 significantly increased in the right hemisphere irrespective of the physical characteristics of the visual stimuli. Conversely, we did not detect the M170 when the face image was suppressed in the BR condition, although this component was clearly present when awareness for the face was initiated. We also found a significant difference in the latency of the M170 (human